JP2008507261A - Novel nucleotide and amino acid sequences for lung cancer diagnosis, and assays and methods of use thereof - Google Patents

Abstract

  Highly sensitive and accurate novel marker for lung cancer. These markers are specifically overexpressed in lung cancer in contrast to normal lung tissue. Measurement of these markers, alone or in combination, in patient samples provides information that can be correlated with a diagnostic predictor of lung cancer. The markers of the present invention, alone or in combination, highly discriminate and detect lung cancer and non-cancerous states.

Description

FIELD OF THE INVENTION The present invention relates to novel nucleotide and protein sequences that are diagnostic markers for lung cancer and to assays and methods of use thereof.

BACKGROUND OF THE INVENTION Lung cancer is the leading cause of cancer death in men and women in the United States, with an estimated 172,000 new cases reported in 1994. The 5-year survival rate for all lung cancer patients is only 13%, regardless of the stage at diagnosis. This is in contrast to the 5-year survival rate of 46% of detected cases where disease is still localized. However, only 16% of lung cancers are found before the spread of the disease. Lung cancer is broadly classified into small cell lung cancer or non-small cell lung cancer. Non-small cell lung cancer is further classified into adenocarcinoma, bronchoalveolar-alveolar, squamous cell carcinoma, and large cell carcinoma. Approximately 75-85% of lung cancers are non-small cell lung cancer and 15-25% are small cell lung cancer.

  Early detection is difficult because clinical symptoms are often not observed until the disease has reached an advanced stage. Currently, diagnosis uses chest x-ray, analysis of cell types contained in sputum, and bronchial fiberscope testing. The treatment plan is determined by the type and stage of the cancer, and the treatment plan includes surgery, radiation therapy, and / or chemotherapy.

  Early detection of primary disease, metastatic disease, and recurrent disease can significantly affect the prognosis of individuals suffering from lung cancer. Non-small cell lung cancer diagnosed at an early stage has significantly better results than those diagnosed at a more advanced stage. Similarly, early diagnosis of small cell lung cancer also has the potential for better prognosis.

  Although current radiotherapeutic agents, chemotherapeutic agents, and biotoxins are potent cytotoxins, they do not distinguish between normal and malignant cells and produce side effects and dose limiting toxicity. Lung cancer specific cancer markers are still needed. There remains a need for reagents and kits that can be used to detect the presence of lung cancer markers in patient derived samples. There remains a need for methods of screening and diagnosing individuals with lung cancer, as well as responses to treatment of patients diagnosed with lung cancer, disease progression, and methods of monitoring disease recurrence. There remains a need for reagents, kits, and methods for determining the type of lung cancer in individuals with lung cancer. There is still a need for compositions that can specifically target lung cancer cells. There remains a need for contrast agents that can specifically bind to lung cancer cells. There remains a need for improved methods of imaging lung cancer cells. There remains a need for therapeutic agents that can specifically bind to lung cancer cells. There remains a need for improved methods of treating individuals suspected of having lung cancer.

SUMMARY OF THE INVENTION The background art neither teaches nor suggests sufficiently sensitive and / or accurate markers for lung cancer, alone or in combination.

  The present invention overcomes these shortcomings of the background art by providing a novel marker for lung cancer that is sensitive and accurate. Furthermore, these markers can distinguish different lung cancer types such as small cell lung cancer or non-small cell lung cancer, and further distinguish non small cell lung cancer types such as adenocarcinoma, squamous cell carcinoma and large cell cancer Can. These markers are specifically overexpressed in lung cancer in contrast to normal lung tissue. Measurement of these markers alone or in combination in patient (biological) samples provides information that can be correlated with the diagnosis of a lung cancer that a diagnostician would expect. The marker of the present invention is highly differentially detected between lung cancer and non-cancerous condition alone or in combination.

  According to a preferred embodiment of the present invention, examples of suitable biological samples which can optionally be used with the preferred embodiment of the present invention include blood, serum, plasma, blood cells, urine, sputum, saliva, feces , Cerebrospinal fluid or CSF, lymph fluid, exocrine skin, airway, intestine, and urogenital tract, tears, milk, nervous tissue, lung tissue, any human organ or tissue (any tumor tissue or normal tissue, obtained by lavage Including, but not limited to, any (eg, bronchial or thoracic duct) samples and samples of in vivo cell culture components. In a preferred embodiment, the biological sample comprises lung tissue and / or sputum and / or serum sample and / or urine sample and / or any other tissue or fluid sample. The sample can optionally be diluted with an appropriate eluting agent prior to contacting the sample with the antibody and / or performing any other diagnostic assay.

  The information given in the text on cellular localization was determined according to the following four different software programs: (i) tmhmm (Center for Biological Sequence Analysis, Technical University of Denmark DTU, for the prediction of transmembrane regions) http://www.cbs.dtu.dk/services/TMHMM/TMHMM2.0b.guide.php) or (ii) tmpred (ISREC Bionformatics group and the LICR Information Technology Office, Ludwig Institute for Cancer Research, Swiss Inst EMBnet maintained by tute of Bioinformatics, http://www.ch.embnet.org/software/TMPRED_form.html; (iii) signalp_hmm or (iv) signalp_nn for signal peptide prediction (both, Center for Biological Sequence Analysis Technical University of Denmark DTU, from http://www.cbs.dtu.dk/services/SignalP/background/prediction.php) The terms "signalp_hmm" and "signalp_nn" refer to two for the program SignalP Hmm means Hidden Markov Model, nn means neural network, also by manual inspection of known protein localization and / or gene structure and also by the use of heuristics by each inventor In some cases, for the manual examination of cell localization prediction, we used the ProLoc calculation platform (Einat Hazkani-Covo, Erez Levanon, Galit Rotman, Dan Graur and Amit Novik; (2004). “Evolution of multicellularity in metazoa: comparative analysis of the subcellular localization of protee ns in Saccharomyces, Drosophila and Caenorhabditis. Using Cell Biology International 2004; 28 (3): 171-8.), This platform has various parameters (eg, the protein domain (eg, the transmembrane domain in the protein and its localization expected), pI, Protein length, amino acid composition, homology to previously annotated proteins, recognition of sequence patterns (NLS, mitochondrial localization signals etc.) that direct the proteins to certain organelles, signal peptides The protein localization is predicted based on and modeling of the anchor, as well as the use of a unique domain specific to Pfam specific to a single compartment.

  Information can be obtained from text on SNPs (single nucleotide polymorphisms). An explanation of the abbreviations is given below. "T-> C" means, for example, that the position given in the table by the SNP changes from T to C. Similarly, "M-> Q" means, for example, that a methionine (M) in the corresponding amino acid sequence has been changed to guanine (Q) by SNP. The presence of a space instead of the right-hand letter of the nucleotide sequence SNP indicates that a frame shift has occurred. Frame shifts can also be indicated by a hyphen (-). The stop codon is indicated to the right with an asterisk (*). As part of the description of the SNP, comments can be found in parentheses after the above description of the SNP itself. This comment may include FTId, which is an identifier for a SwissProt entry created using the ANP shown. The FTId is a unique and stable feature identifier, which directly builds a link from the location specific annotation in the feature table to a specialized protein related database. FTId is always the last component of the feature in the Description field: FTId = XXX_number (XXX is a three letter representation of a particular feature key separated by an underscore from a 6 digit number). In the table of amino acid mutations of wild-type proteins of selected splice variants of the present invention, the header on the first line is "the position of the SNP on the amino acid sequence" and indicates the position of the known mutation on the amino acid sequence . The SNPs can be used as diagnostic markers of the present invention, optionally, alone or in combination with one or more other SNPs and / or any other diagnostic markers. Preferred embodiments of the invention include such SNPs (the SNPs on the known (WT or wild type) protein sequences as shown below as well as novel nucleic acid and / or amino acid sequences formed by such SNPs, and And / or includes, but is not limited to, any SNPs on the variant amino acid sequences and / or nucleic acid sequences described herein.

The information given in the text for homology with known proteins was determined by Smith-Waterman version 5.1.2 using the following specific (non-default) parameters:
-Model = sw. model
-GAPEXT = 0
-GAPOP = 100.0
-MATRIX = blosum 100

Information is obtained on the overexpression of clusters in cancer based on EST. The clues to the p value for such overexpression analysis are:

Library-based statistics: P-values without expression levels in cell lines (P1)
Library based statistics: P value including expression level in cell lines (P2)
-EST clone statistics: P value without expression level in cell lines (SP1)
-EST clone statistics: estimated overexpression rate (R3) without expression level in cell lines
-EST clone statistics: P value including expression level in cell line (SP2)
-EST clone statistics: estimated overexpression rate (R4), including expression levels in cell lines

  Library-based statistics refers to statistics across all libraries, EST clonal statistics refers to expression only for ESTs from a particular tissue or cancer.

Information is obtained on the overexpression of clusters in cancer based on microarrays. As a reference of the microarray, in a specific segment paragraph, a non-omitted tissue name was used as a reference of the chip type whose expression was measured. There are two types of microarray results: Microarray-derived types prepared by the design according to the present invention (Microarray construction procedures are detailed in the section "Materials and Experimental Procedures" herein) and Microarray-derived type using Affymetrix technology. As a microarray standard, in a specific segment paragraph, non-omitted tissue names were used as a standard for the chip type whose expression was measured. For microarrays prepared according to the design according to the invention, the probe names start with the cluster (gene) name and follow the identification number. The oligonucleotide microarray results obtained from the Affymetrix data were from a chip available from Affymetrix Inc, Santa Clara, CA, USA (e.g. Human Genome at www.affymetrix.com/products/arrays/specific/hgu133.affx U133 (HG-U133) Set; www.affymetrix.com/products/arrays/specific/hgu133av2.affx GeneChip Human Genome U133A 2.0 Array; and www.affymetrix.com/products/arrays/specific/hgu133plus.affx Hu an Genome U133 Plus 2.0 see data on Array). Probe names follow the Affymetrix naming convention. Data are available from NCBI Gene Expression Omnibus (www.ncbi.nlm.nih.gov/projects/geo/ and Edgar et al, Nucleic Acids Research, 2002, Vol. 30, No. 1207-210) It is possible. The data set (including results) of the Series GSE1133 database (released in March 2004) is www. ncbi. nlm. nih. gov / geo / query / acc. cgi? acc = GSE1133 available; references for these results are: Su et al (Proc Natl Acad Sci USA A. 2004 Apr 20; 101 (16): 6062-7. Epub 2004 Apr 09). The probes designed by the inventor are listed below.

> H61775_0_11_0
CCCCAGCTTTTATAGAGCGGGCCCAAGGAAAGATATTTCCAGAAGTAGGG
> M85491_0_0_25999
GACATCTTTGCATATCATGTCAGAGCTATAACATCATTGTGGAGAAGCTC
> M85491_0_14_0
GTCATGAAAATCAACACCGAGGTGCGGAGCTTCGGACCTGTGTCCCGCAG
> Z21368_0_0_61857
AGTTCATCCTTCTTCAGTGTGACCAGTAAATTCTTCCCATACTCTTGAAG
> HUMGRP5E_0_0_16630
GCTGATATGGAAGTTGGGGAATCTGAATTGCCAGAGAATCTTGGGAAGAG
> HUMGRP5E_0_2_0
TCTCATAGAAGCAAGAGGAGACAGAAACCACCAGCCACCTCAACCCAAGG
> D56406_0_5_0
TCTGACTTTTACGGACTTGGCTTGTTAGAGGCAGAAGATGATGGCAGG
> F05068_0_0_5744
ACGGGAGGGA AGGA AGGTGTGCGGAGGAGGTTTCTGCTCCACTCCCCT
> F05068_0_0_5754
CAAGGGGAACTGACCGTTGGTCCCGAAGGTCTAGAAGTGAATGGGAGCAG
> F05068_0_8_0
CTGGGCTTGGACTTCGGAGTTTGCCATTGCCAGTGGGACGTCTGAGACT
> F05068_0_1_5751
TCTTAGCAGGTAGGTGCGCGCAGACCCTGCGGGTTAAGAGGTGGGGTGGGG
> H38804_0_3_0
CGTAATTGCAGTGCATTTAGACAGGCATCTATTTGGACCTGTTTCTATCT
> HSENA 78_0_1_0
TGAAGAGTGTGAGAAAACCTATGTTTGCGCCTTAAAGCTTTCAGCTCAGC
> R00299_0_8_0
CCAAGGCTCGTCTGCGCACCTTGTGTCTTGTAGGGTATGGTATGTGGGAC
> Z44808_0_8_0
AAAAGCATGAGTTTCTGACCAGCGTTCTGGACGCGCTGTCCACGGACATG
> Z44808_0_0_72347
ATGTTCTTAGGAGGCAAGCCAGGAGAAGCCGGGTCTGACTTTTCAGCTCA
> Z44808_0_0_72349
TCCTCCAGACCCAAAGCCACAACCCATCGCAAGTCAAGAACACTTTCCAG
> AA161187_0_0_433
ACCCTGGGTGGGCAAAAACGTGCTTCCCGGACGGGGTTGAAGGGGAGAA
> AA161187_0_0_430
TGGAGACTGTTGCCCCACTCTGCAGATGCAGAACGGAGGCTTGGCTGCT
> R66178_0_7_0
CCAGTGTGGTATCCTGGGAAACTCTGGTTAAAGGTGAGGCAGAGTACCAG
> HUMPHOSLIP_0_0_18458
AAGGAAGCAGGACCAGTGGATGTGAGGCGTGGTCGAAGAACAACAGAAAG
> HUMPHOSLIP_0_0_18487
ACAGGGGCCAGATGGTGACCCATGACCCAGCCTAAAAGGCAGCCAAGAGGG
> AI076020_0_3_0
ATCAGCACTGCCACCTACACCACGGTGCCGCGCGTGGCCTTCTAC GCCGG
> T23580_0_0_902
GTGAAACCCCATTGGCTTCATTGGCTCCTTGATTTAAACCACGCCCGGCT
> T23580_0_0_901
TGAGTCCCGTGTTATATCATCTGGTCTCATTGATAGGCGGGATAGGGAGGG
> M79217_0_9_0
TTTGTGGAATAGCAACCCATGGTTATGGCGAGTGACCCGACGTGATCTGG
> M62096_0_0_20588
AAGGCTTAGGTGCAAAGCCATTGGATACCATACCTGAGACCACACAGCACA
> M62096_0_7_0
ACCAGAAGCTGTCCAGACTCCGAGACGAAATTGAGGGAGAAGCAGAAA
> M78076_0_7_0
GAGAAGATGAACCCGCTGGAACAGTATGAGCGAAAGGTGAATGCGTCTGT
> T99080_0_0_58896
AACTC AC AGCA AG AGC TG TTTCC AG TT AT AGC TT T CT CCAC GT GT GC AG
> T08446_0_9_0
CATTTCCACTACGAGAACGTTGACTTTGGCCACATTCAGCTCCTGCTGTC
> HUMCA1XIA_0_0_14909
GCTGCAATCTAAGTTTCGGAATACTTATACCACTCCAGAAATAATATCTCG
> HUMCA1XIA_0_18_0
TTCAGAACTGTTAACATCGCTGACGGGAAGTGGCATCGGGTAGCAATCAG
> T11628_0_9_0
ACAAG ATCC CCGTGA AG TACTCTGGAGTT CATCTCGGAATGCAT CATCCAG
> T11628_0_0_45174
TAAAACAATCAAAGAGCATGTTGGCCTGGCTCCTTTGCTAGGTACTGTAGAG
> T11628_0_0_45161
TGCCTCGCCACAAGTGGCACCTGCCCCTAAAATAGCTTCCCATGTGAGGCT
> HUMCEA_0_0_96
CAAGAGGGGTTTGGCTGAGACTTTAGGATTGTGATTCAGCTTAGAGGGAC
> HUMCEA_0_0_15183
CCTGGTGGAGCCCATGAGAAGCGAGTTTCTGTGCAACGGACTTAGTAA
> HUMCEA_0_0_15182
GCTCCCTGGAGCATCAGCATCATATTCTGGGGTGGAGTCTATCTGGTTCT
> HUMCEA_0_0_15168
TCCTGCCTGTCACCTGAAGTTCTAGATCATTCCCTGGACTCCACTCTATC
> HUMCEA_0_0_15180
TTTAACACAGGGATTGGGACAGGATTCAGAGGGACACTGTGGCCCTTCTAC
> R35137_0_5_0
TATGTGGAGGTGGTGAACATGGACGCTGCAGTGCAGCACAGATGCTGAA
> Z25299_0_3_0
AACTCTGGGCACCTTGGGCTGTGGAAGCTCTGGAAGTCCTTCAAAGCTG
> HSSTROL3_0_0_12518
ATGAGAGTAACTCTCCACCCGTGCACTAGTTTAGAGACATTCACTGCCCCA
> HSSTROL3_0_0_12517
CAGAGATGAGAGCCTGGAGCATTGCAGATGCGAGGACTTCACAAATGAA
> HSS100PCB_0_0_12280
CTC AAAATGA AACTCC CT CTC GC AGAGCACAAATTCCAATTCGCTCTAAAA
> R20779_0_0_30670
CCGCGTTGCTTCTAGAGGCTGAATGCCTTTC AAATGGAGAAGGCTTCCAT

The following list of tissue abbreviations was used in the TAA histogram: The term "TAA" refers to "tumor associated antigen" and the TAA histogram shown in the text, as detailed in Examples 1-5 below, shows the cancer tissue expression pattern predicted by the biomarker selection engine Show.
"BONE" is "bone";
"COL" is "colon";
"EPI" is "epithelial";
"GEN" is "general";
"LIVER" is the "liver";
"LUN" is "lung";
"LYMPH" is a "lymph node";
"MARROW" is the "bone marrow";
"OVA" is "ovary";
"PANCREAS" is "pancreas";
"PRO" is "prostate";
"STOMACH" is "stomach";
"TCELL" is "T cell";
"THYROID" is the "thyroid";
"MAM" is "breast";
"BRAIN" is the "brain";
"UTERUS" is "the womb";
"SKIN" is "skin";
"KIDNEY" is the "kidney";
"MUSCLE" is "muscle";
"ADREN" is the "adrenal gland";
"HEAD" is "head and neck";
"BLADDER" is the "bladder".

  It should be noted that the terms "segment", "seg" and "node" are used interchangeably with respect to the nucleic acid sequences of the invention, which may have one or more of the following properties Refers to a portion of the indicated nucleic acid sequence. These are also the building blocks used to construct complete nucleic acid sequences, as described in more detail below. Optionally and preferably, these are embodiments of the invention (e.g. as an amplicon, as a hybridization unit), and / or optionally from which primers and / or complementary oligonucleotides are optionally derived. An example of an oligonucleotide for well and / or any other use.

  As used herein, the phrase "lung cancer" refers to lung cancer including small cell lung cancer and non-small cell lung cancer including, but not limited to, lung adenocarcinoma, squamous cell carcinoma, and adenocarcinoma Say).

  The term "marker" in the context of the present invention refers to lung cancer (or indicative condition) as compared to a comparable sample taken from a subject not afflicted with lung cancer (or one of the above mentioned conditions). And nucleic acid fragments, peptides or polypeptides which are present differently in a sample taken from a subject (patient) suffering from

  The phrase “differently present” refers to a patient suffering from lung cancer (or one of the indicative conditions) as compared to a comparable sample taken from a patient not suffering from lung cancer (or one of the above conditions) The amount of marker present in the sample taken from is different. For example, as determined by hybridization and / or NAT-based assays, the nucleic acid fragments optionally have two samples if the amount of nucleic acid fragments in one sample is significantly different from the amount of nucleic acid fragments in the other sample. There may be differences between them. Polypeptides are present differently between two samples if the amount of polypeptide in one sample is significantly different from the amount of polypeptide in the other sample. It should be noted that if a marker is detectable in one sample but not in the other sample, such a marker can be considered to be present differently.

  As used herein, the phrase "diagnosis" means the identification of the presence or nature of a pathological condition. Diagnostic methods differ in their sensitivity and specificity. The "sensitivity" of a diagnostic assay is the proportion of diseased individuals who show a positive response (the proportion of "true positives"). Affected individuals not detected by the assay will be "false negatives". Subjects who do not suffer and who test positive in the assay are termed "true negatives". The “specificity” of a diagnostic assay is the 1-false positive rate (where “false negative” rate is defined as the proportion of non-diseased subjects who show a positive response). Although certain diagnostic methods may not reliably diagnose the condition, it is sufficient if the method provides a clear indication to aid the diagnosis.

  As used herein, the phrase "diagnosis" refers to classification of a disease or condition, determination of the severity of the disease, monitoring of the progression of the disease, prediction of the outcome of the disease and / or the likelihood of recovery. The term "detection" may also optionally include any of the above.

  Diagnosis of a disease of the invention can be made by determination of polynucleotide or polypeptide levels of the invention in a biological sample obtained from a subject, and the determined level can be correlated with a predisposition to the disease or the presence or absence of a disease. . It should be noted that "a biological sample obtained from a subject" may also optionally include a sample that has not been physically removed from the subject, as described in further detail below.

  As used herein, the term "level" refers to the DNA copy number of the expression level or marker of the RNA and / or protein of the present invention.

  Typically, the level of markers in a biological sample obtained from a subject is different (i.e. more or less) from the level of the same variant in similar samples obtained from healthy individuals (examples of biological samples are , As described herein).

  Using a number of well-known tissue or fluid collection methods to collect a biological sample from a subject and to determine the level of the mutant DNA, RNA, and / or polypeptide of interest in the subject it can.

  Examples include, but are not limited to, fine needle biopsy, needle biopsy, core needle biopsy, and surgical biopsy (eg, brain biopsy), and lavage. Regardless of the procedure used, once a biopsy / sample is obtained, the level of the variant can be determined and thereby diagnosed.

  Preferably, the determination of the level of the same variant in normal tissue of the same origin is carried out simultaneously in order to detect an increase in expression and / or amplification of the variant in contrast to normal tissue and / or a decrease in expression.

  The "test dose" of a marker refers to the amount of marker in a subject sample consistent with the diagnosis of lung cancer (or one of the indicative conditions). The test amount can be either an absolute amount (eg, μg / ml) or a relative amount (eg, relative intensity of signal).

  The "control amount" of a marker can be any amount or range of amounts to be compared to the test amount of the marker. For example, the control amount of the marker can be that of the lung cancer (or one of the indicating condition) patients or the marker of a human not afflicted with lung cancer (or one of the indicating conditions). Control amounts can be either absolute amounts (eg, μg / ml) or relative amounts (eg, relative intensity of signal).

  "Detection" refers to the identification of the presence, absence or amount of the object to be detected.

A "label" includes any part or item detectable by microscopic means, photochemical means, biochemical means, immunochemical means, or chemical means. For example, useful labels include ³² P, ³⁵ S, fluorochromes, electron-dense reagents, enzymes (eg, commonly used in ELISA), biotin-streptavidin, dioxigenin, antisera or monoclonal antibodies Possible haptens and proteins, or nucleic acid molecules complementary in sequence to the target are included. Labels often produce measurable signals such as radioactive, chromogenic or fluorescent signals, which can be used to quantify the amount of bound label in a sample. The label can be incorporated into or attached to the primer or probe by either covalent, ionic, van der Waals, or hydrogen bonding (eg, biotinylated as recognized by radioactive nucleotides or streptavidin) Nucleotide incorporation). The label can be detected directly or indirectly. Indirect detection can include direct or indirect attachment of a second label to the first label. For example, the label can be a ligand of binding partner such as biotin which is a binding partner of streptavidin or a nucleotide sequence which is a binding partner of a complementary sequence capable of specifically hybridizing. The binding partner itself can be detected directly, for example the antibody itself can be labeled with a fluorescent molecule. The binding partner can also be detected indirectly, eg, a nucleic acid having a complementary nucleotide sequence can be part of a branched DNA molecule which can be detected by hybridization with another labeled nucleic acid molecule (eg, See P. D. Fahrlander and A. Klausner, Bio / Technology 6: 1165 (1988)). For example, signal is quantified by scintillation counting, densitometry, or flow cytometry.

  Exemplary detectable labels for use with optional and preferably immunoassays include magnetic beads, fluorochromes, radioactive labels, enzymes (such as horseradish peroxidase, alkaline phosphatase, and commonly used in ELISAs) And other enzymes, and calorimetric labels (such as colloidal gold or colored glass), or plastic beads, but not limited thereto. Alternatively, a marker in the sample is used in an indirect assay (eg, using a second labeled antibody to detect bound marker specific antibody) and / or a competition assay or an inhibition assay (eg, of the marker) The monoclonal antibodies that bind to different epitopes can be detected simultaneously with the mixture).

  An "immunoassay" is an assay that uses an antibody that specifically binds an antigen. Immunoassays are characterized by the use of specific binding properties of a particular antibody to isolate, target, and / or quantify antigen.

  The phrase "specifically (or selectively) binds" to an antibody or "specifically (or selectively) immunoreactive with" refers to a protein or peptide (or other epitope) , A binding reaction that determines the presence of a protein in a heterogeneous population of proteins or other biologics. Thus, under designated immunoassay conditions, the particular antibody binds to the particular protein at least twice background (nonspecific signal) and in significant amounts to other proteins present in the sample It does not bind substantially. Specific binding of an antibody under such conditions may require an antibody selected for its specificity for a particular protein. For example, a polyclonal antibody raised against semen basic protein from a specific species such as rat, mouse, or human is selected to specifically immunoreact with semen basic protein, but other proteins It is possible to obtain only polyclonal antibodies which do not react with the polymorphic protein variants and alleles). This selection can be made by subtracting antibodies that cross-react with semen basic protein molecules from other species. Various immunoassay formats can be used to select antibodies that exhibit specific immunoreactivity with a particular protein. For example, solid-phase ELISA immunoassays are routinely used to select antibodies that exhibit specific immunoreactivity with a protein (eg, a format of immunoassay that can be used to detect specific immunoreactivity) And for a description of the conditions see Harlow & Lane, Antibodies, A Laboratory Manual (1988)). Typically, the specific or selective reaction is at least twice background signal or noise, more typically 10 to 100 times background.

  According to a preferred embodiment of the present invention, preferably, any of the above nucleic acid sequences and / or amino acid sequences are at least about 70%, preferably at least about 80%, more preferably at least about 90%, most Preferably, it further comprises any sequence that is at least about 95% homologous.

  Unless otherwise indicated, all experimental data are named according to the segment tested for the variants of the invention (when expression is tested by RT-PCR as described).

  All nucleic acid and / or amino acid sequences set forth herein as embodiments of the present invention are in isolated form (including isolated polynucleotides, including all transcripts), oligonucleotides (all segments, amplicons) , And primers, peptides (all tails, crosslinks, insertions, or tips (optionally including other antibody epitopes described herein), and / or polypeptides (whole protein) Is included)). It should be noted that oligonucleotides and polynucleotides or peptides and polypeptides can optionally be used interchangeably.

  According to a preferred embodiment of the present invention there is provided an isolated polynucleotide comprising SEQ ID NO: 1 and 2.

  According to a preferred embodiment of the present invention, there is provided an isolated polynucleotide comprising SEQ ID NOs: 1022, 1023, 1024, 1025, 1026 and 1027.

  According to a preferred embodiment of the present invention there is provided an isolated polypeptide comprising SEQ ID NO: 1281 and 1282.

  According to a preferred embodiment of the present invention, there is provided an isolated polynucleotide comprising SEQ ID NO: 3 and 4.

  According to a preferred embodiment of the present invention, there is provided an isolated polynucleotide comprising SEQ ID NOs: 1028, 1029, 1030, 1031, 1032, 1033, 1034, 1034, 1035, 1036, 1037 and 1038.

  According to a preferred embodiment of the present invention there is provided an isolated polypeptide comprising SEQ ID NO: 1283 and 1284.

  According to a preferred embodiment of the present invention, there is provided an isolated polynucleotide comprising SEQ ID NO: 5, 6, 7 and 8.

  According to a preferred embodiment of the present invention, SEQ ID NO: 1039, 1040, 1041, 1042, 1043, 1045, 1046, 1047, 1048, 1049, 1050, 1051, 1052, 1053, 1054, 1055, 1056, 1057, Provided are isolated polynucleotides comprising 1058, 1059, 1060, 1061, 1062, 1063, 1064, 1065, and 1066.

  According to a preferred embodiment of the present invention there is provided an isolated polypeptide comprising SEQ ID NOs: 1285, 1286, 1287 and 1288.

  According to a preferred embodiment of the present invention, there is provided an isolated polynucleotide comprising SEQ ID NOs: 9, 10, 11, 12, 13, 14, and 15.

  According to a preferred embodiment of the present invention, SEQ ID NO: 1067, 1068, 1069, 1070, 1071, 1072, 1073, 1074, 1075, 1076, 1077, 1078, 1079, 1080, 1081, 1082, 1083, 1084, 1085, Provided are isolated polynucleotides comprising 1086, 1087, 1088, 1089, 1090, 1091, 1092, 1093, 1094, 1095, 1096, 1097, 1098, 1099, and 1100.

  According to a preferred embodiment of the present invention, there is provided an isolated polypeptide comprising SEQ ID NOs: 1289, 1290, 1291, 1292, 1293 and 1294.

  According to a preferred embodiment of the present invention there is provided an isolated polynucleotide comprising SEQ ID NO: 20 and 21.

  According to a preferred embodiment of the present invention, there is provided an isolated polynucleotide comprising SEQ ID NOs: 1130, 1131, 1132, 1133 and 1134.

  According to a preferred embodiment of the present invention there is provided an isolated polypeptide comprising SEQ ID NO: 1299 and 1300.

  According to a preferred embodiment of the present invention, there is provided an isolated polynucleotide comprising SEQ ID NO: 22, 23 and 24.

  According to a preferred embodiment of the present invention, there is provided an isolated polynucleotide comprising SEQ ID NOs: 1135, 1136, 1137, 1138, 1139, 1140, 1141, 1142, 1143, and 1144.

  According to a preferred embodiment of the present invention, there is provided an isolated polypeptide comprising SEQ ID NOs: 1301, 1302 and 1303.

  According to a preferred embodiment of the present invention there is provided an isolated polynucleotide comprising SEQ ID NO: 25, 26 and 27.

  According to a preferred embodiment of the present invention, there is provided an isolated polynucleotide comprising SEQ ID NOs: 1145, 1146, 1147, 1148, 1149, 1150, 1151, 1152, 1153, 1154, 1155, and 1156.

  According to a preferred embodiment of the present invention there is provided an isolated polypeptide comprising SEQ ID NOs: 1304 and 1305.

  According to a preferred embodiment of the present invention there is provided an isolated polynucleotide comprising SEQ ID NO: 28.

  According to a preferred embodiment of the present invention, there is provided an isolated polynucleotide comprising SEQ ID NOs: 1157, 1158, 1159, 1160, 1161, 1162, 1163, 1164, 1165, 1166, 1167, 1168, 1169, 1170, and 1171. Do.

  According to a preferred embodiment of the present invention there is provided an isolated polypeptide comprising SEQ ID NO: 1306.

  According to a preferred embodiment of the present invention there is provided an isolated polynucleotide comprising SEQ ID NO: 29 and 30.

  According to a preferred embodiment of the present invention, SEQ ID NO: 1172, 1173, 1174, 1176, 1177, 1178, 1179, 1180, 1181, 1182, 1183, 1184, 1185, 1186, 1187, 1188, 1189, 1190, And 1191 is provided.

  According to a preferred embodiment of the present invention there is provided an isolated polypeptide comprising SEQ ID NOs: 1307 and 1308.

  According to a preferred embodiment of the present invention there is provided an isolated polynucleotide comprising SEQ ID NO: 31.

  According to a preferred embodiment of the present invention, there is provided an isolated polynucleotide comprising SEQ ID NOS: 1192, 1193, 1194, 1195, 1196, 1197, and 1198.

  According to a preferred embodiment of the present invention there is provided an isolated polypeptide comprising SEQ ID NO: 1309.

  According to a preferred embodiment of the present invention there is provided an isolated polynucleotide comprising SEQ ID NO: 32.

  According to a preferred embodiment of the present invention, an isolation comprising SEQ ID NOs: 1199, 1200, 1201, 1202, 1203, 1204, 1205, 1206, 1207, 1208, 1210, 1211, 1212, 1213, 1214, and 1215 Provide a polynucleotide.

  According to a preferred embodiment of the present invention there is provided an isolated polypeptide comprising SEQ ID NO: 1310.

  According to a preferred embodiment of the present invention there is provided an isolated polynucleotide comprising SEQ ID NO: 33.

  According to a preferred embodiment of the present invention, there are provided isolated polynucleotides comprising SEQ ID NOs: 1216 and 1217, 1218, 1219, 1220, 1221, 1222, 1223, 1224, 1225, 1225, 1226, and 1227.

  According to a preferred embodiment of the present invention there is provided an isolated polypeptide comprising SEQ ID NO: 1311.

  According to a preferred embodiment of the present invention there is provided an isolated polynucleotide comprising SEQ ID NO: 34.

  According to a preferred embodiment of the present invention, there is provided an isolated polynucleotide comprising SEQ ID NO: 1228, 1229, 1230, 1231, 1232 and 1223.

  According to a preferred embodiment of the present invention there is provided an isolated polypeptide comprising SEQ ID NO: 1312.

  According to a preferred embodiment of the present invention there is provided an isolated polynucleotide comprising SEQ ID NO: 35.

  According to a preferred embodiment of the invention SEQ ID NO: 1234, 1235, 1236, 1238, 1239, 1240, 1241, 1242, 1243, 1244, 1245, 1246, 1247, 1248, 1249, 1249, 1250, 1251, 1252, An isolated polynucleotide comprising 1253, and 1254 is provided.

  According to a preferred embodiment of the present invention there is provided an isolated polypeptide comprising SEQ ID NO: 1313.

  According to a preferred embodiment of the present invention there is provided an isolated polynucleotide comprising SEQ ID NOs: 36, 37, 38, 39 and 40.

  According to a preferred embodiment of the present invention, SEQ ID NO: 1255, 1256, 1257, 1258, 1259, 1260, 1261, 1262, 1263, 1264, 1265, 1266, 1267, 1268, 1269, 1270, 1271, 1272, 1273, Provided is an isolated polynucleotide comprising 1274 and 1275.

  According to a preferred embodiment of the present invention there is provided an isolated polypeptide comprising SEQ ID NOs: 1314, 1315, 1316 and 1317.

  According to a preferred embodiment of the present invention, there is provided an isolated polynucleotide comprising SEQ ID NO: 125, 126, 127, 128, 129 and 130.

  According to a preferred embodiment of the present invention, an isolated polynucleotide comprising SEQ ID NOs: 887, 888, 889, 890, 891, 892, 893, 894, 895, 896, 897, 898, 899, 900, 901, and 902. I will provide a.

  According to a preferred embodiment of the present invention there is provided an isolated polypeptide comprising SEQ ID NO: 1394, 1395, 1396, 1397, and 1398.

  According to a preferred embodiment of the present invention, there is provided an isolated polynucleotide comprising a transcript of SEQ ID NO: 131 and 132.

  According to a preferred embodiment of the present invention, there is provided an isolated polynucleotide comprising SEQ ID NOs: 903, 904, 905, 906, 907, 907, 908 and 909.

  According to a preferred embodiment of the present invention there is provided an isolated polypeptide comprising SEQ ID NOs: 1399 and 1400.

  According to a preferred embodiment of the present invention there is provided an isolated polynucleotide comprising SEQ ID NO: 99, 100, 101 and 102.

  According to a preferred embodiment of the present invention, SEQ ID NOs: 742, 743, 744, 745, 746, 747, 749, 750, 751, 752, 753, 754, 755, 756, 757, 758, 759, 760, 761, 762, 763, 764, 765, 766, 767, 768, 769, 770, 771, 772, 773, 775, 776, 777, 778, 779, 781, 782, 783, 784, 785, Provided are isolated polynucleotides comprising 786, 787, and 788.

  According to a preferred embodiment of the present invention there is provided an isolated polypeptide comprising SEQ ID NOs: 1372, 1373, 1374 and 1375.

  According to a preferred embodiment of the present invention there is provided an isolated polynucleotide comprising SEQ ID NO: 134.

  According to a preferred embodiment of the present invention, SEQ ID NOs: 913, 914, 915, 916, 917, 918, 919, 920, 921, 922, 924, 925, 926, 927, 928, 929, 930, 931, Provided are isolated polynucleotides comprising 932, 933, 934, 935, and 936.

  According to a preferred embodiment of the present invention there is provided an isolated polypeptide comprising SEQ ID NO: 1402.

  According to a preferred embodiment of the present invention there is provided an isolated polynucleotide comprising SEQ ID NO: 133.

  According to a preferred embodiment of the present invention, there is provided an isolated polynucleotide comprising SEQ ID NO: 910, 911 and 912.

  According to a preferred embodiment of the present invention there is provided an isolated polynucleotide comprising SEQ ID NO: 141, 142 and 142.

  According to a preferred embodiment of the present invention, SEQ ID NO: 961, 962, 963, 964, 966, 966, 968, 969, 970, 971, 972, 974, 975, 976, 977, 978, 979, Provided are isolated polynucleotides comprising 980, 981, 982, 983, 984, 985, 986, 987, 988, 989, and 990.

According to a preferred embodiment of the present invention, the protein name:
HUMOSTRO_PEA_1_PEA_1_P21,
HUMOSTRO_PEA_1_PEA_1_P25,
Provided is an isolated polypeptide comprising HUMOSTRO_PEA_1_PEA_1_P30.

  According to a preferred embodiment of the present invention there is provided an isolated polynucleotide comprising SEQ ID NOs: 51, 52, 53, 54, 55, 56 and 57.

  According to a preferred embodiment of the present invention, SEQ ID NOs: 518, 519, 520, 521, 522, 523, 524, 526, 527, 528, 529, 530, 531, 532, 533, 534, 535, 536, 537, 538, 539, 540, 541, 542, 543, 544, 545, 546, 547, 548, 549, 550, 552, 553, 554, 555, 556, 557, 558, 559, 560, 561, Provided are isolated polynucleotides comprising 562, 563, 564, 565, 566, 567, 568, 569, and 570.

  According to a preferred embodiment of the present invention there is provided an isolated polypeptide comprising SEQ ID NOs: 1327, 1328, 1329, 1330, 1331, 1332, and 1333.

  According to a preferred embodiment of the present invention, there is provided an isolated polynucleotide comprising SEQ ID NOs: 135, 136, 137, 138, 139 and 140.

  According to a preferred embodiment of the present invention, SEQ ID NO: 937, 938, 939, 940, 941, 942, 943, 944, 945, 946, 947, 948, 949, 950, 951, 952, 953, 953, 954, 955, Provided are isolated polynucleotides comprising 956, 957, 958, 959, and 960.

  According to a preferred embodiment of the present invention, there is provided an isolated polypeptide comprising SEQ ID NO: 1403, 1404, 1405, 1406, 1407, and 1408.

  According to a preferred embodiment of the present invention, there is provided an isolated polynucleotide comprising SEQ ID NOs: 41, 42, 43, 44, 45, 46 and 47.

  According to a preferred embodiment of the present invention, SEQ ID NO: 482, 483, 484, 495, 486, 487, 488, 489, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500, And an isolated polynucleotide comprising 501.

  According to a preferred embodiment of the present invention there is provided an isolated polypeptide comprising SEQ ID NOs: 1318, 1319, 1320, 1321, 1322 and 1323.

  According to a preferred embodiment of the present invention, there is provided an isolated polynucleotide comprising SEQ ID NOs: 121, 122, 123 and 124.

  According to a preferred embodiment of the present invention, there is provided an isolated polynucleotide comprising SEQ ID NO: 876, 877, 878, 879, 880, 881, 882, 883, 884, 885, and 886.

  According to a preferred embodiment of the present invention there is provided an isolated polypeptide comprising SEQ ID NOs: 1390, 1391, 1392 and 1393.

  According to a preferred embodiment of the present invention, there is provided an isolated polynucleotide comprising SEQ ID NO: 48, 49, and 50.

  According to a preferred embodiment of the present invention, an isolated polynucleotide comprising SEQ ID NOs: 502, 503, 504, 505, 506, 507, 508, 509, 510, 511, 512, 513, 514, 515, 516, and 517. I will provide a.

  According to a preferred embodiment of the present invention, there is provided an isolated polypeptide comprising SEQ ID NO: 1324, 1325 and 1326.

  According to a preferred embodiment of the present invention there is provided an isolated polynucleotide comprising SEQ ID NO: 1464 and 1465.

  According to a preferred embodiment of the present invention, there is provided an isolated polynucleotide comprising SEQ ID NO: 1276, 1277, 1278, 1279, and 1280.

  According to a preferred embodiment of the present invention there is provided an isolated polypeptide comprising SEQ ID NO: 1415.

Protein names corresponding to transcripts:
HSU33147_PEA_1_P5; HSU33147_PEA_1_T1; HSU33147_PEA_1_T2.

  According to a preferred embodiment of the present invention there is provided an isolated polynucleotide comprising SEQ ID NO: 58.

  According to a preferred embodiment of the present invention there is provided an isolated polynucleotide comprising SEQ ID NOs: 571, 572, 573, 574, 575, 576, 577 and 578.

  According to a preferred embodiment of the present invention, there is provided an isolated polypeptide comprising SEQ ID NO: 1334.

  According to a preferred embodiment of the present invention, there is provided an isolated polynucleotide comprising SEQ ID NO: 74, 75, 76, 77, 78, 79, 80, 81 and 82.

  According to a preferred embodiment of the present invention, SEQ ID NOs: 659, 660, 661, 662, 662, 664, 665, 666, 667, 669, 670, 671, 672, 673, 674, 675, 676, 677, Provided are isolated polynucleotides comprising 678, 679, 680, 681, 682, 683, 684, 685, 686, 687, 688, 689, 690, 691, 692, and 693.

  According to a preferred embodiment of the present invention, there is provided an isolated polypeptide comprising SEQ ID NOs: 1350, 1351, 1352, 1353, 1354, 1355, 1356, and 1357.

  According to a preferred embodiment of the present invention there is provided an isolated polynucleotide comprising SEQ ID NO: Transcript name T23580_T10.

  According to a preferred embodiment of the present invention there is provided an isolated polynucleotide comprising SEQ ID NO: 579, 580, 581, 582, and 583.

  According to a preferred embodiment of the present invention there is provided an isolated polypeptide comprising SEQ ID NO: 1335.

  According to a preferred embodiment of the present invention, there is provided an isolated polynucleotide comprising SEQ ID NO: 59, 60, 61, 62, 63 and 64.

  According to a preferred embodiment of the present invention, SEQ ID NO: 584, 585, 586, 587, 588, 589, 590, 591, 592, 593, 594, 595, 596, 597, 598, 599, 600, 601, 602, Provided are isolated polynucleotides comprising 603, 604, 605, 606, 607, 608, 609, 610, 611, 612, 613, 614, and 615.

  According to a preferred embodiment of the present invention there is provided an isolated polypeptide comprising SEQ ID NOs: 1336, 1337, 1338, 1339, and 1340.

  According to a preferred embodiment of the present invention, there is provided an isolated polynucleotide comprising SEQ ID NO: 65, 66, 67, 68, 69, 70, 71, 72 and 73.

  According to a preferred embodiment of the present invention, SEQ ID NOs: 616, 617, 618, 619, 620, 621, 622, 623, 624, 626, 627, 628, 629, 630, 631, 632, 633, 634, 635, 636, 637, 638, 639, 640, 641, 642, 643, 644, 645, 646, 647, 649, 650, 651, 652, 653, 654, 655, 656, 657, 658, and 659 Providing an isolated polynucleotide comprising

  According to a preferred embodiment of the present invention, there is provided an isolated polypeptide comprising SEQ ID NOs: 1341, 1342, 1343, 1344, 1345, 1346, 1347, 1348 and 1349.

  According to a preferred embodiment of the present invention, there is provided an isolated polynucleotide comprising SEQ ID NO: 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, and 96.

  According to a preferred embodiment of the present invention, there is provided an isolated polynucleotide comprising SEQ ID NO: 695, 696, 697, 698, 699, 700, 701, 702, 703, 704 and 705.

  According to a preferred embodiment of the present invention, there is provided an isolated polypeptide comprising SEQ ID NOs: 1358, 1359, 1360, 1361, 1362, 1363, 1364, 1365, 1366, 1367, 1368, and 1369.

  According to a preferred embodiment of the present invention, there is provided an isolated polynucleotide comprising SEQ ID NO: 97 and 98.

  According to a preferred embodiment of the present invention, SEQ ID NOs: 706, 707, 708, 709, 710, 711, 712, 714, 715, 716, 717, 719, 720, 721, 722, 722, 724, Provided are isolated polynucleotides comprising 725, 726, 727, 728, 729, 730, 731, 732, 733, 734, 735, 736, 737, 738, 739, 740, and 741.

  According to a preferred embodiment of the present invention there is provided an isolated polypeptide comprising SEQ ID NOs: 1370 and 1371.

  According to a preferred embodiment of the present invention, there is provided an isolated polynucleotide comprising SEQ ID NOs: 103, 104, 105, 106, 107 and 108.

  According to a preferred embodiment of the present invention, SEQ ID NO: 789, 790, 791, 792, 792, 793, 794, 795, 796, 797, 798, 799, 800, 801, 802, 803, 804, 805, 806, 807, Provided are isolated polynucleotides comprising 808, 809, 810, 811, 812, and 813.

  According to a preferred embodiment of the present invention there is provided an isolated polypeptide comprising SEQ ID NO: 1376, 1377, 1378 and 1379.

  According to a preferred embodiment of the present invention, there is provided an isolated polynucleotide comprising SEQ ID NOs: 114, 115, 116, 117, 118 and 119.

  According to a preferred embodiment of the present invention, SEQ ID NO: 856, 857, 858, 859, 860, 861, 862, 863, 864, 866, 867, 868, 869, 870, 871, 872, 873, 874, And an isolated polynucleotide comprising 875.

  According to a preferred embodiment of the present invention there is provided an isolated polypeptide comprising SEQ ID NO: 1385, 1386, 1387, 1388, and 1389.

  According to a preferred embodiment of the present invention there is provided an isolated polynucleotide comprising SEQ ID NO: 144, 145, 146, 147, 148 and 149.

  According to a preferred embodiment of the present invention, SEQ ID NO: 991, 992, 993, 994, 995, 996, 997, 998, 999, 1000, 1001, 1002, 1003, 1004, 1005, 1006, 1007, 1008, 1009, Provided are isolated polynucleotides comprising 1010, 1011, 1012, 1013, 1014, 1015, and 1016.

  According to a preferred embodiment of the present invention there is provided an isolated polypeptide comprising SEQ ID NOs: 1409, 1410, 1411, 1412 and 1413.

  According to a preferred embodiment of the present invention there is provided an isolated polynucleotide comprising SEQ ID NO: 150.

  According to a preferred embodiment of the present invention, there is provided an isolated polynucleotide comprising SEQ ID NOs: 1017, 1018, 1019, 1020 and 1021.

  According to a preferred embodiment of the present invention there is provided an isolated polypeptide comprising SEQ ID NO: 1414.

  According to a preferred embodiment of the present invention, there is provided an isolated polynucleotide comprising SEQ ID NOs: 109, 110, 111, 112 and 113.

  According to a preferred embodiment of the present invention, SEQ ID NOs: 814, 815, 816, 817, 818, 819, 820, 821, 822, 823, 824, 825, 826, 827, 829, 830, 831, 832, 833, An isolated polynucleotide comprising 834, 835, 836, 837, 838, 839, 840, 841, 842, 843, 844, 845, 846, 847, 848, 849, 850, 851, 852, 853, 854, and 855. I will provide a.

  According to a preferred embodiment of the present invention, there is provided an isolated polypeptide comprising SEQ ID NOs: 1380, 1381, 1382, 1383 and 1384.

  According to a preferred embodiment of the present invention, the isolated chimeric polypeptide encoding HSSTROL3_P4, which corresponds to amino acids 1 to 163 of MM11 _HUMAN and also corresponds to amino acids 1 to 163 of HSSTROL3 _P4, corresponds to The first amino acid sequence, the bridging amino acid H corresponding to amino acid 164 of HSSTROL3_P4, and the amino acid of MM11_HUMAN It corresponds to Amino Acids 165-445, JididieruPiefudiJipijijiaierueieichieiefuefuPikeitieichiaruijidibuieichiefudiwaidiitidaburyutiaijididikyujitidieruerukyubuieieieichiiefujieichibuierujierukyueichititieieikeieieruemuesueiefuwaitiefuaruwaiPieruesueruesuPididishiarujibuikyueichieruwaijikyuPidaburyuPitibuitiesuarutiPieieruJipikyueijiaiditienuiaieiPieruiPidieiPiPidieishiieiesuefudieibuiesutiaiarujiieruefuefuefukeieijiefubuidaburyuarueruarujijikyuerukyuPijiwaiPieierueiesuarueichidaburyukyujieruPiesupibuidieieiefuidieikyujieichiaidaburyuefuefukyujieikyuwaidaburyubuiwaidijiikeiPibuieruJipiEipierutiierujierubuiaruefuPibuieichieieierubuidaburyuJipiikeienukeiaiwaiefuefuarujiarudiwaidaburyuaruefueichiPiesutiaruarubuidiesuPVPRRATDWRGVPSEIDAAFQDADG at least 90 corresponding to amino acids 165-445 of HSSTROL3_P4 A polypeptide having at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% with a polypeptide having the homologous second amino acid sequence and the sequence ALGVRQLVGGGHSSRFSHLV VAGLPHACHRKSGSSSQVLPPEPSALLSVAG corresponding to amino acids 446 to 496 of HSSTROL3_P4. Most preferably, it comprises at least a 95% homologous third amino acid sequence, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence, and third amino acid sequence are adjacent and in sequential order Provided is an isolated chimeric polypeptide encoding HSSTROL3_P4.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of HSSTROL3_P4, which is at least 70%, optionally at least about 80%, preferably at least about 85%, with the sequence ALGVRQLVGGGHSSRFSHLVVAGLPHACHRKSGSSSQVCLEPPSALLSVAG in HSSTROL3_P4. More preferably, an isolated polypeptide encoding the tail of HSSTROL3_P4 is provided that comprises a polypeptide that is at least about 90%, and most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, the isolated chimeric polypeptide encoding HSSTROL3_P5, which corresponds to amino acids 1 to 163 of MM11 _HUMAN and also corresponds to amino acids 1 to 163 of HSSTROL3 _P5. The first amino acid sequence, the bridging amino acid H corresponding to amino acid 164 of HSSTROL3_P5, and the amino acid of MM11_HUMAN Corresponds to Amino Acids 165-358, corresponding GDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWTIGDDQGTDLLQVAAHEFGHVLGLQHTTAAKALMSAFYTFRYPLSLSPDDCRGVQHLYGQPWPTVTSRTPALGPQAGIDTNEIAPLEPDAPPDACEASFDAVSTIRGELFFFKAGFVWRLRGGQLQPGYPALASRHWQGLPSPVDAAFEDAQGHIWFFQ and at least 90% homologous to a second amino acid sequence to amino acids 165-358 of HSSTROL3_P5, the polypeptide having a sequence corresponding to ELGFPSSTGRDESLEHCRCQGLHK to amino acid 359-382 of HSSTROL3_P5 At least 70 A third amino acid sequence, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous, said first amino acid sequence being a bridging amino acid, Provided is an isolated chimeric polypeptide encoding HSSTROL3_P5, wherein the two amino acid sequences and the third amino acid sequence are adjacent and in sequential order.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of HSSTROL3_P5, comprising at least 70%, optionally at least about 80%, preferably at least about 85% of the sequence ELGFPSSTGRDESLEHCRCQGLHK in HSSTROL3_P5. More preferably, provided is an isolated polypeptide encoding the tail of HSSTROL3_P5, comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, the isolated chimeric polypeptide encoding HSSTROL3_P7, which corresponds to amino acids 1 to 163 of MM11 _HUMAN and to amino acids 1 to 163 of HSSTROL3 _P7, also corresponds to The first amino acid sequence, the bridging amino acid H corresponding to amino acid 164 of HSSTROL3_P7, and the amino acid of MM11_HUMAN Corresponds to Amino Acids 165-359, corresponding GDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWTIGDDQGTDLLQVAAHEFGHVLGLQHTTAAKALMSAFYTFRYPLSLSPDDCRGVQHLYGQPWPTVTSRTPALGPQAGIDTNEIAPLEPDAPPDACEASFDAVSTIRGELFFFKAGFVWRLRGGQLQPGYPALASRHWQGLPSPVDAAFEDAQGHIWFFQG and at least 90% homologous to a second amino acid sequence to amino acids 165-359 of HSSTROL3_P7, the polypeptide having a sequence corresponding to TTGVSTPAPGV to amino acid 360-370 of HSSTROL3_P7 At least 70%, optionally at least The first amino acid sequence, the bridging amino acid, the second amino acid sequence, and the third amino acid sequence that is 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous; Provided is an isolated chimeric polypeptide encoding HSSTROL3_P7, wherein the third amino acid sequence is in a contiguous and sequential order.

  According to a preferred embodiment of the invention, an isolated polypeptide encoding the tail of HSSTROL3_P7, comprising at least 70%, optionally at least about 80%, preferably at least about 85%, of the sequence TTGVSTPAPGV in HSSTROL3_P7. More preferably, provided is an isolated polypeptide encoding the tail of HSSTROL3_P7, comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, the isolated chimeric polypeptide encoding HSSTROL3_P8, which corresponds to amino acids 1 to 163 of MM11 _HUMAN and also corresponds to amino acids 1 to 163 of HSSTROL3 _P8. The first amino acid sequence, the bridging amino acid H corresponding to amino acid 164 of HSSTROL3_P8, and the amino acid of MM11_HUMAN GDLPDFPGGILAHAFFFPKTHREGDVHFDYDETTIDDDQGTDLLQVAAHEFGHVLQQHTTAAKALMSAFYTFRYPLSDGRDQQTPRTPSIPLGPIP GILPTQGTPQGPRTPSIPL GELPFET A signal that corresponds to at least 90% of the other members of the network. 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous a third amino acid sequence, 1 amino acid sequence, crosslinked amino acid, the second amino acid sequence, and a third amino acid sequence, contiguous and in sequential order, provides an isolated chimeric polypeptide coding HSSTROL3_P8.

  According to a preferred embodiment of the invention, an isolated polypeptide encoding the tail of HSSTROL3_P8, comprising at least 70%, optionally at least about 80%, preferably at least about 85%, of the sequence VRPCLPVPLLLCWPL in HSSTROL3_P8. More preferably, provided is an isolated polypeptide encoding the tail of HSSTROL3_P8, comprising a polypeptide that is at least about 90%, and most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding HSSTROL3_P9, which corresponds to amino acids 1 to 96 of MM11 HUMAN and also to amino acids 1 to 96 of HSSTROL3_P9. RIRLFPWQLVQEQVRQTMAEALKVWSDVTPL TFTEVHEGRAMIDI FARYW corresponding to the first amino acid sequence and amino acids 113 to 163 of MM11_HUMAN and also to amino acids 97 to 147 of HSSTROL3_P9 Homologous second amino acid sequence, a crosslinking amino acids H corresponding to amino acid 148 of HSSTROL3_P9, corresponding to amino acids 165-359 of MM11_HUMAN, first of at least 90% homologous to the corresponding GDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWTIGDDQGTDLLQVAAHEFGHVLGLQHTTAAKALMSAFYTFRYPLSLSPDDCRGVQHLYGQPWPTVTSRTPALGPQAGIDTNEIAPLEPDAPPDACEASFDAVSTIRGELFFFKAGFVWRLRGGQLQPGYPALASRHWQGLPSPVDAAFEDAQGHIWFFQG to amino acids 149-343 of HSSTROL3_P9 Amino acid sequence of 3, and HSSTROL3_P9 A fourth amino acid sequence that is at least 70%, optionally at least 80%, preferably at least 85%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous to a polypeptide having the sequence TTGVSTPAPGV corresponding to amino acid 344 And wherein the first amino acid sequence, the second amino acid sequence, the bridging amino acid, the third amino acid sequence, and the fourth amino acid sequence are adjacent and in a sequential order, the isolation encoding HSSTROL3_P9 Provided is a chimeric polypeptide.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding the edge portion of HSSTROL3_P9, having a length "n", wherein n is at least about 10 amino acids in length, optionally Of at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length, and most preferably at least about 50 amino acids in length); Structure: having a sequence beginning with any of amino acid numbers 96-x to 96 and ending with amino acid number 97 + ((n-2) -x), wherein x varies from 0 to n-2 Provided is an isolated chimeric polypeptide encoding the rim portion of HSSTROL3_P9, which comprises the polypeptide.

  According to a preferred embodiment of the invention, an isolated polypeptide encoding the tail of HSSTROL3_P9, comprising at least 70%, optionally at least about 80%, preferably at least about 85%, of the sequence TTGVSTPAPGV in HSSTROL3_P9. Provided is an isolated polypeptide encoding the tail of HSSTROL3_P9, more preferably comprising a polypeptide that is at least about 90%, and most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding HUMCA1XIA_P14, corresponds to amino acids 1 to 1056 of CA1B_HUMAN_V5, corresponding to amino acids 1 to 1056 of HUMCA1XIA_P14 MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNSPEGISKTTGFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFSILFTVKPKKGIQSFLLSIYNEHGIQQIGVEVGRSPVFLFEDHTGKPAPEDYPLFRTVNIADGKWHRVAISVEKKTVTMIVDCKKKTTKPLDRSERAIVDTNGITVFGTRILDEEVFEGDIQQ LITGDPKAAYDYCEHYSPDCDSSAPKAAQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVTEGPTVTEETIAQTEANIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDSQRKNSEDTLYENKEIDGRDSDLLVDGDLGEYDFYEYKEYEDKPTSPPNEEFGPGVPAETDITETSINGHGAYGEKGQKGEPAVVEPGMLVEGPPGPAGPAGIMGPPGLQGPTGPPGDPGDRGPPGRPGLPGADGLPGPPGTMLMLPFRYGGDGSKGPTISAQEAQAQAILQQARIALRGPPGPMGLTGRPGPVGGPGSSGAKGES DPGPQGPRGVQGPPGPTGKPGKRGRPGADGGRGMPGEPGAKGDRGFDGLPGLPGDKGHRGERGPQGPPGPPGDDGMRGEDGEIGPRGLPGEAGPRGLLGPRGTPGAPGQPGMAGVDGPPGPKGNMGPQGEPGPPGQQGNPGPQGLPGPQGPIGPPGEKGPQGKPGLAGLPGADGPPGHPGKEGQSGEKGALGPPGPQGPIGYPGPRGVKGADGVRGLKGSKGEKGEDGFPGFKGDMGLKGDRGEVGQIGPRGEDGPEGPKGRAGPTGDPGPSGQAGEKGKLGVPGLPGYPGRQGPKGSTGFPGFPGANGEKGARGVAGKPGPRGQRGPTGPRG A first amino acid sequence at least 90% homologous to EsuarujieiaruJipitijikeiPiJipikeijitiesujijidiJipipijipipijiiaruJipikyuJipikyuJipibuijiefupijipikeiJipipijipipijikeidijierupijieichipijikyuarujiitijiefukyujikeitijipipiJipijijibuibuiJipikyuJipitijiitiJipiaijiiarujieichiPiJipipijipipijiikyujieruPijieieijikeiijieikeijidipiJipikyujiaiesujikeidiJipieijieruarujiefuPijiiRGLPGAQGAPGLKGGEGPQGPPGPV, polypeptide at least 70% with a sequence corresponding to VSMMIINSQTIMVVNYSSSFITLML to amino acid 1057 to 1081 of HUMCA1XIA_P14, optionally at least 80%, preferably at least 85%, more preferably Is at least 90%, most preferably at least 95% homologous And a amino acid sequence, the first amino acid sequence and a second amino acid sequence, contiguous and in sequential order, provides an isolated chimeric polypeptide coding HUMCA1XIA_P14.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of HUMCA1XIA_P14, comprising at least 70%, optionally at least about 80%, preferably at least about 85% of the sequence VSMMIINSQTIMVVNYSSSFITLML in HUMCA1XIA_P14 More preferably, provided is an isolated polypeptide encoding the tail of HUMCA1XIA_P14, comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding HUMCA1XIA_P15, corresponding to amino acids 1-714 of CA1B_HUMAN, corresponding to amino acids 1-714 of HUMCA1XIA_P15 MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNSPEGISKTTGFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFSILFTVKPKKGIQSFLLSIYNEHGIQQIGVEVGRSPVFLFEDHTGKPAPEDYPLFRTVNIADGKWHRVAISVEKKTVTMIVDCKKKTTKPLDRSERAIVDTNGITVFGTRILDEEVFEGDIQQFLITG PKAAYDYCEHYSPDCDSSAPKAAQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVTEGPTVTEETIAQTEANIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDSQRKNSEDTLYENKEIDGRDSDLLVDGDLGEYDFYEYKEYEDKPTSPPNEEFGPGVPAETDITETSINGHGAYGEKGQKGEPAVVEPGMLVEGPPGPAGPAGIMGPPGLQGPTGPPGDPGDRGPPGRPGLPGADGLPGPPGTMLMLPFRYGGDGSKGPTISAQEAQAQAILQQARIALRGPPGPMGLTGRPGPVGGPGSSGAKGESGDPGP A first amino acid sequence at least 90% homologous to JipiarujibuikyujipipiJipitijikeiPijikeiarujiaruPijieidijijiarujiemuPijiiPijieikeijidiarujiefudijieruPijieruPijidikeijieichiarujiiaruJipikyuJipipijipipijididijiemuarujiidijiiaiJipiarujieruPijiieiJipiarujierueruJipiarujitiPijieiPijikyuPijiemueijibuidijipipiJipikeijienuemuJipikyujiiPiJipiPGQQGNPGPQGLPGPQGPIGPPGEK, polypeptide at least 70% with a sequence corresponding to MCCNLSFGILIPLQK to amino acid 715-729 of HUMCA1XIA_P15, optionally at least 80%, preferably at least 85%, more preferably Comprises a second amino acid sequence which is at least 90%, most preferably at least 95% homologous, said first amino acid sequence The present invention provides an isolated chimeric polypeptide encoding HUMCA1XIA_P15, wherein the second amino acid sequence is in a contiguous and sequential order.

  According to a preferred embodiment of the invention, an isolated polypeptide encoding the tail of HUMCA1XIA_P15, comprising at least 70%, optionally at least about 80%, preferably at least about 85%, of the sequence MCCNLSFGILIPLQK in HUMCA1XIA_P15. More preferably, provided is an isolated polypeptide encoding the tail of HUMCA1XIA_P15, comprising a polypeptide that is at least about 90%, and most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding HUMCA1XIA_P16, corresponding to amino acids 1-648 of CA1B_HUMAN, corresponding to amino acids 1-648 of HUMCA1XIA_P16 MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNSPEGISKTTGFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFSILFTVKPKKGIQSFLLSIYNEHGIQQIGVEVGRSPVFLFEDHTGKPAPEDYPLFRTVNIADGKWHRVAISVEKKTVTMIVDCKKKTTKPLDRSERAIVDTNGITVFGTRILDEEVFEGDIQQFLITG PKAAYDYCEHYSPDCDSSAPKAAQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVTEGPTVTEETIAQTEANIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDSQRKNSEDTLYENKEIDGRDSDLLVDGDLGEYDFYEYKEYEDKPTSPPNEEFGPGVPAETDITETSINGHGAYGEKGQKGEPAVVEPGMLVEGPPGPAGPAGIMGPPGLQGPTGPPGDPGDRGPPGRPGLPGADGLPGPPGTMLMLPFRYGGDGSKGPTISAQEAQAQAILQQARIALRGPPGPMGLTGRPGPVGGPGSSGAKGESGDPGP The first amino acid sequence at least 90% homologous to JipiarujibuikyujipipiJipitijikeiPijikeiarujiaruPijieidijijiarujiemuPijiiPijieikeijidiarujiefudijieruPijieruPijidikeijieichiarujiiaruJipikyuJipiPGPPGDDGMRGEDGEIGPRGLPGEA, corresponding to amino acids 667-714 of CA1B_HUMAN, corresponding GMAGVDGPPGPKGNMGPQGEPGPPGQQGNPGPQGLPGPQGPIGPPGEK and at least 90% homologous to a second amino acid sequence, the HUMCA1XIA_P16 to amino acids 649-696 of HUMCA1XIA_P16 At least 70% with the polypeptide having the sequence VSFSFSLFYKKVIKFACDKRFVGRHDERKVVKLSLPLYLIYE corresponding to amino acids 697-738, Said first amino acid sequence, said second amino acid sequence comprising a third amino acid sequence, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous And a third amino acid sequence, in contiguous and sequential order, provides an isolated chimeric polypeptide encoding HUMCA1XIA_P16.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding the rim portion of HUMCA1XIA_P16, having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length, most preferably at least about 50 amino acids in length), wherein at least two amino acids comprise AG; A polypeptide having a sequence beginning with any of the numbers 648-x-648 and ending with the amino acid number 649 + ((n-2) -x), wherein x varies from 0 to n-2. Provided is an isolated chimeric polypeptide encoding an edge portion of HUMCA1XIA_P16, including:

  According to a preferred embodiment of the invention, an isolated polypeptide encoding the tail of HUMCA1XIA_P16, comprising at least 70%, optionally at least about 80%, preferably at least about 85%, of the sequence VSFSFSLFYKKVIKFACDKRFVGRHDERKVVKLSLPLYLIYE in the sequence HUMCA1XIA_P16 More preferably, provided is an isolated polypeptide encoding the tail of HUMCA1XIA_P16, comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding HUMCA1XIA_P17, corresponding to amino acids 1-260 of CA1B_HUMAN, corresponding to amino acids 1-260 of HUMCA1XIA_P17 MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNSPEGISKTTGFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFSILFTVKPKKGIQSFLLSIYNEHGIQQIGVEVGRSPVFLFEDHTGKPAPEDYPLFRTVNIADGKWHRVAISVEKKTVTMIVDCKKKTTKPLDRSERAIVDTNGITVFGTRILDEEVFEGDIQQFLITG At least 70%, optionally at least 80%, preferably at least 85%, more preferably a first amino acid sequence at least 90% homologous to PKAAYDYCEHYSPDCDSSAPKAAQAQEPQIDE and the sequence VRSTRPEKVFVFQ corresponding to amino acids 261 to 273 of HUMCA1XIA_P17 Comprises HUMCA1XIA_P17, comprising a second amino acid sequence which is at least 90%, most preferably at least 95% homologous, said first amino acid sequence and said second amino acid sequence being adjacent and in sequential order An isolated chimeric polypeptide is provided.

  According to a preferred embodiment of the invention, an isolated polypeptide encoding the tail of HUMCA1XIA_P17, comprising at least 70%, optionally at least about 80%, preferably at least about 85%, of the sequence VRSTRPEKVFVFQ in HUMCA1XIA_P17 More preferably, an isolated polypeptide encoding the tail of HUMCA1XIA_P17, comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, according to a preferred embodiment of the present invention, the R20779.Ph. The first amino acid sequence and the sequence CYKIEITMPKRRKVK corresponding to amino acids 170 to 187 of R20779_P2 A polypeptide having RD and a second amino acid sequence which is at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous; Provided is an isolated chimeric polypeptide encoding R20779_P2 in which the amino acid sequence of 1 and the second amino acid sequence are adjacent and in sequential order.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of R20779_P2, comprising at least 70%, optionally at least about 80%, preferably at least about 85% of the sequence CYKIEITMPKRRKVKLRD in R20779_P2 More preferably, provided is an isolated polypeptide encoding the tail of R20779_P2, comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding HUMOSTRO_PEA_1_PEA_1_P21, corresponding to amino acids 1 to 58 of OSTP_HUMAN and also corresponding to amino acids 1 to 58 of HUMOSTRO_PEA_1_PEA_1_P21 At least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably a polypeptide having the first amino acid sequence and the sequence VFLNFS corresponding to amino acids 59 to 64 of HUMOSTRO_PEA_1_PEA_1_P21 Is at least 95 And a homologous second amino acid sequence, the first amino acid sequence and a second amino acid sequence, contiguous and in sequential order, provides an isolated chimeric polypeptide coding HUMOSTRO_PEA_1_PEA_1_P21.

  According to a preferred embodiment of the invention, an isolated polypeptide encoding the tail of HUMOSTRO_PEA_1_PEA_1_P21, comprising at least 70%, optionally at least about 80%, preferably at least about 85%, of the sequence VFLNFS in HUMOSTRO_PEA_1_PEA_1_P21 More preferably, provided is an isolated polypeptide encoding the tail of HUMOSTRO_PEA_1_PEA_1_P21, comprising a polypeptide that is at least about 90%, and most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding HUMOSTRO_PEA_1_PEA_1_P25, which is at least 90% homologous to MRIAVICFCLLGITCAIPVKQADSGSSEEKQ, which corresponds to amino acids 1 to 31 of OSTP_HUMAN and also to amino acids 1 to 31 of HUMOSTRO_PEA_1_PEA_1_P25. The polypeptide having the first amino acid sequence and the sequence H corresponding to amino acids 32-32 of HUMOSTRO_PEA_1_PEA_1_P25 and at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably Comprises a second amino acid sequence which is at least 95% homologous, said first amino acid sequence and 2 amino acid sequences, contiguous and in sequential order, provides an isolated chimeric polypeptide coding HUMOSTRO_PEA_1_PEA_1_P25.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding HUMOSTRO_PEA_1_PEA_1_P30, which is at least 90% homologous to MRIAVICFCLLGITCAIPVKQADSGSSEEKQ, which corresponds to amino acids 1 to 31 of OSTP_HUMAN and also to amino acids 1 to 31 of HUMOSTRO_PEA_1_PEA_1_P30. At least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably a polypeptide having the first amino acid sequence and the sequence VSIFYVFI corresponding to amino acids 32-39 of HUMOSTRO_PEA_1_PEA_1_P30 Contains at least a 95% homologous second amino acid sequence, and Acid sequence and a second amino acid sequence, contiguous and in sequential order, provides an isolated chimeric polypeptide coding HUMOSTRO_PEA_1_PEA_1_P30.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of HUMOSTRO_PEA_1_PEA_1_P30, comprising at least 70%, optionally at least about 80%, preferably at least about 85%, of the sequence VSIFYVFI in HUMOSTRO_PEA_1_PEA_1_P30 More preferably, provided is an isolated polypeptide encoding the tail of HUMOSTRO_PEA_1_PEA_1_P30, comprising a polypeptide that is at least about 90%, and most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding HUMPHOSLIP_PEA_2_P10, corresponding to amino acids 1 to 67 of PLTP_HUMAN and also corresponding to amino acids 1 to 67 of HUMPHOSLIP_PEA_2_P10. The first amino acid sequence corresponds to amino acids 163 to 493 of PLTP_HUMAN, and also corresponds to amino acids 68 to 398 of HUMPHOSLIP_PEA_2_P10. KVYDFLSTFITSGMFRNLQQICPVLYHAGTPVLLNSLLDTVPVRSSVDELVIDYSLMKDP ASTSNLDMDFRGAFFPLTERNWSLPNRAVEPQLQEEERMVYVAFSEFFFDSAMESYFRAGALQLLLVGDKVPHDLDMLLRATYFGSIVLLSPAVIDSPLKLELRVLAPPRCTIKPSGTTISVTASVTIALVPPDQPEVQLSSMTMDARLSAKMALRGKALRTQLDLRRFRIYSNHSALESLALIPLQAPLKTMLQIGVMPMLNERTWRGVQIPLPEGINFVHEVVTNHAGFLTIGADLHFAKGLREVIEKNRPADVRASTAPTPSTAAV and and at least 90% homologous to a second amino acid sequence, the sequence of the first amino acid sequence and a second amino acid sequence, adjacent and continuous There provides isolated chimeric polypeptide coding HUMPHOSLIP_PEA_2_P10.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding the rim portion of HUMPHOSLIP_PEA_2_P10, having a length “n”, where n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length, most preferably at least about 50 amino acids in length), wherein at least two amino acids comprise EK; A polypeptide having a sequence beginning with any of the numbers 67-x to 67 and ending with the amino acid number 68 + ((n-2) -x), wherein x varies from 0 to n-2. Provided is an isolated chimeric polypeptide encoding the edge portion of HUMPHOSLIP_PEA_2_P10.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding HUMPHOSLIP_PEA_2_P12, corresponding to amino acids 1-427 of PLTP_HUMAN, corresponding to amino acids 1-427 of HUMPHOSLIP_PEA_2_P12 MALFGALFLALLAGAHAEFPGCKIRVTSKALELVKQEGLRFLEQELETITIPDLRGKEGHFYYNISEVKVTELQLTSSELDFQPQQELMLQITNASLGLRFRRQLLYWFFYDGGYINASAEGVSIRTGLELSRDPAGRMKVSNVSCQASVSRMHAAFGGTFKKVYDFLSTFITSGMRFLLNQQICPVLYHAGTVLLNSLLDTVPVRSSVDELV A first amino acid sequence at least 90% homologous to AidiwaiesueruemukeidiPibuieiesutiesuenuerudiemudiefuarujieiefuefuPierutiiaruenudaburyuesueruPienuarueibuiiPikyuerukyuiiiaruemubuiwaibuieiefuesuiefuefuefudiesueiemuiesuwaiefuarueijieierukyuerueruerubuijidikeibuiPieichidierudiemuerueruarueitiwaiefujiesuaibuierueruesuPieibuiaidiesuPierukeieruieruarubuierueiPiPiarushitiaikeiPiesujititiaiesubuitieiesubuitiaieierubuiPiPidikyuPiibuikyueruesuesuemutiemudieiarueruesueikeiemueieruarujikeieieruarutikyuerudieruaruaruefuaruaiwaiesuenueichiesueieruESLALIPLQAPLKTMLQIGVMPMLN, polypeptide at least 70% with a sequence corresponding to GKAGV to amino acid 428-432 of HUMPHOSLIP_PEA_2_P12, optionally at least 80%, preferably at least 85%, more Good Or encoding HUMPHOSLIP_PEA_2_P12, comprising a second amino acid sequence which is at least 90%, most preferably at least 95% homologous, said first and second amino acid sequences being adjacent and in sequential order An isolated chimeric polypeptide is provided.

  According to a preferred embodiment of the invention, an isolated polypeptide encoding the tail of HUMPHOSLIP_PEA_2_P12, comprising at least 70%, optionally at least about 80%, preferably at least about 85% of the sequence GKAGV in HUMPHOSLIP_PEA_2_P12 More preferably, provided is an isolated polypeptide encoding the tail of HUMPHOSLIP_PEA_2_P12, comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding HUMPHOSLIP_PEA_2_P31, corresponding to amino acids 1 to 67 of PLTP_HUMAN and also corresponding to amino acids 1 to 67 of HUMPHOSLIP_PEA_2_P31. At least 70%, optionally at least 80%, preferably at least 85%, more preferably less with the first amino acid sequence and a polypeptide having the sequence PGLERGADKFPVVGGSLSLALDLTLP PVG corresponding to amino acids 68 to 98 of HUMPHOSLIP_PEA_2_P31 Encoding HUMPHOSLIP_PEA_2_P31, comprising a second amino acid sequence of at least 90%, most preferably at least 95% homology, said first amino acid sequence and said second amino acid sequence being adjacent and in sequential order An isolated chimeric polypeptide is provided.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of HUMPHOSLIP_PEA_2_P31, which is at least 70%, optionally at least about 80%, preferably at least about 85%, with the sequence PGLERGADKFPVVGGSLFLALDLTLPVG in the HUMPHOSLIP_PEA_2_P31 More preferably, provided is an isolated polypeptide encoding the tail of HUMPHOSLIP_PEA_2_P31, comprising a polypeptide that is at least about 90%, and most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding HUMPHOSLIP_PEA_2_P33, corresponding to amino acids 1-183 of PLTP_HUMAN, at least 90% homologous with the corresponding MALFGALFLALLAGAHAEFPGCKIRVTSKALELVKQEGLRFLEQELETITIPDLRGKEGHFYYNISEVKVTELQLTSSELDFQPQQELMLQITNASLGLRFRRQLLYWFFYDGGYINASAEGVSIRTGLELSRDPAGRMKVSNVSCQASVSRMHAAFGGTFKKVYDFLSTFITSGMRFLLNQQ to amino acids 1-183 of HUMPHOSLIP_PEA_2_P33 First amino acid sequence and HUMPHOS At least 70%, optionally at least 80%, preferably at least 85%, preferably at least 90%, more preferably at least 90%, most preferably at least 95% homologous to a polypeptide having the sequence VWAATGRRVARVGMLSL corresponding to amino acids 184 to 200 of IP_PEA_2_P33 An isolated chimeric polypeptide encoding HUMPHOSLIP_PEA_2_P33, comprising two amino acid sequences, wherein the first and second amino acid sequences are adjacent and in sequential order.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of HUMPHOSLIP_PEA_2_P33, comprising at least 70%, optionally at least about 80%, preferably at least about 85%, of the sequence VWAATGRRVARVGMLSL in HUMPHOSLIP_PEA_2_P33 More preferably, provided is an isolated polypeptide encoding the tail of HUMPHOSLIP_PEA_2_P33, comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding HUMPHOSLIP_PEA_2_P34, corresponding to amino acids 1-205 of PLTP_HUMAN, the corresponding MALFGALFLALLAGAHAEFPGCKIRVTSKALELVKQEGLRFLEQELETITIPDLRGKEGHFYYNISEVKVTELQLTSSELDFQPQQELMLQITNASLGLRFRRQLLYWFFYDGGYINASAEGVSIRTGLELSRDPAGRMKVSNVSCQASVSRMHAAFGGTFKKVYDFLSTFITSGMRFLLNQQICPVLYHAGTVLLNSLLDTVPV to amino acids 1-205 of HUMPHOSLIP_PEA_2_P34 least 90 At least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, of a polypeptide having the sequence LWTSLLALTIPS corresponding to amino acids 206 to 217 of HUMPHOSLIP_PEA_2_P34 with the homologous first amino acid sequence An isolated chimeric polypeptide encoding HUMPHOSLIP_PEA_2_P34, comprising a second amino acid sequence that is most preferably at least 95% homologous, said first amino acid sequence and the second amino acid sequence being in contiguous and sequential order I will provide a.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of HUMPHOSLIP_PEA_2_P34, comprising at least 70%, optionally at least about 80%, preferably at least about 85% of the sequence LWTSLLALTIPS in HUMPHOSLIP_PEA_2_P34 More preferably, provided is an isolated polypeptide encoding the tail of HUMPHOSLIP_PEA_2_P34, comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding HUMPHOSLIP_PEA_2_P35, corresponding to amino acids 1-109 of PLTP_HUMAN and also corresponding to amino acids 1-109 of HUMPHOSLIP_PEA_2_P35, MALGFALFLAKALVTKALEQQEGL LTIQETIELIT7 is a UT The first amino acid sequence, the second amino acid sequence, the bridging amino acid H including L, and the amino acids 163 to 183 of PLTP_HUMAN, and the amino acids 111 to 1 of HUMPHOSLIP_PEA_2_P35 And at least 70%, optionally at least 80%, preferably at least 80%, with a polypeptide having the third amino acid sequence at least 90% homologous to KVYDFLSTFITSGMFRNLQQ and the sequence VWAATGRRVARVGMLSL corresponding to amino acids 132-148 of HUMPHOSLIP_PEA_2_P35. Said first amino acid sequence, the second amino acid sequence, the third amino acid sequence, and the fourth amino acid sequence comprising a fourth amino acid sequence that is 85%, more preferably at least 90%, most preferably at least 95% homologous; Provided is an isolated chimeric polypeptide encoding HUMPHOSLIP_PEA_2_P35, wherein the amino acid sequences are in contiguous and sequential order.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding the rim portion of HUMPHOSLIP_PEA_2_P35, having a length “n”, where n is at least about 10 amino acids long, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length, most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise FLK and have the following structure (HUMPHOSLIP_PEA_2_P35 Numbering corresponding to: beginning with any of amino acid numbers 109-x to 109 and ending with amino acid number 111 + ((n-2) -x), where x varies from 0 to n-2 Comprising a polypeptide, having a sequence, HUMPHOSLIP_P It provides an isolated chimeric polypeptide coding edges of A_2_P35.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of HUMPHOSLIP_PEA_2_P35, comprising at least 70%, optionally at least about 80%, preferably at least about 85%, of the sequence VWAATGRRVARVGMLSL in HUMPHOSLIP_PEA_2_P35 More preferably, provided is an isolated polypeptide encoding the tail of HUMPHOSLIP_PEA_2_P35, comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding R38144_PEA_2_P6, corresponding to amino acids 1-412 of CT31_HUMAN, corresponding to amino acids 1-412 of R38144_PEA_2_P6 MPFRLLIPLGLLCALLPQHHGAPGPDGSAPDPAHYRERVKAMFYHAYDSYLENAFPFDELRPLTCDGHDTWGSFSLTLIDALDTLLILGNVSEFQRVVEVLQDSVDFDIDVNASVFETNIRVVGGLLSAHLLSKKAGVEVEAGWPCSGPLLRMAEEAARKLLPAFQTPTGMPYGTVNLLHGVNPGETPVTCTAGIGTFIVEFATLSSLTGDPVFEDVARVALM A first amino acid sequence at least 90% homologous to ErudaburyuiesuaruesudiaijierubuijienueichiaidibuierutijikeidaburyubuieikyudieijiaijieijibuidiesuwaiefuiwaierubuikeijieiaieruerukyudikeikeieruemueiemuefueruiwaienukeieiaiaruenuwaitiaruefudididaburyuwaierudaburyubuikyuemuwaikeijitibuiesuemuPibuiefukyuesueruieiwaidaburyuPijierukyuesueruaijidiaidienueiemuarutiefueruenuwaiwaitibuidaburyukeikyuefujijieruPiiefuwaienuaiPikyujiwaitibuiikeiaruijiwaiPieruaruPiieruaiiesueiemuwaieruwaiarueitijidipiTLLELGRDAVESIEKISKVECGFAT, polypeptide at least 70% with a sequence corresponding to LASFSHMSDQRSARPQAGQPHGVVLPGRDCEIPLPPV to amino acid 413-449 of R38144_PEA_2_P6, optionally at least 80%, preferably at least 85%, Preferably, it encodes R38144_PEA_2_P6, which comprises a second amino acid sequence which is at least 90%, most preferably at least 95% homologous, said first amino acid sequence and the second amino acid sequence being adjacent and in sequential order An isolated chimeric polypeptide is provided.

  According to a preferred embodiment of the invention, an isolated polypeptide encoding the tail of R38144_PEA_2_P6, comprising at least 70%, optionally at least about 80%, preferably at least about 85%, of the sequence LASFSHMSDQRSARPQAGQPHGVVLPGRDCEIPLPPV in R38144_PEA_2_P6 More preferably, provided is an isolated polypeptide encoding the tail of R38144_PEA_2_P6, comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding R38144_PEA_2_P13, corresponding to amino acids 1-323 of CT31_HUMAN, corresponding to amino acids 1-323 of R38144_PEA_2_P13 MPFRLLIPLGLLCALLPQHHGAPGPDGSAPDPAHYRERVKAMFYHAYDSYLENAFPFDELRPLTCDGHDTWGSFSLTLIDALDTLLILGNVSEFQRVVEVLQDSVDFDIDVNASVFETNIRVVGGLLSAHLLSKKAGVEVEAGWPCSGPLLRMAEEAARKLLPAFQTPTGMPYGTVNLLHGVNPGETPVTCTAGIGTFIVEFATLSSLTGDPVFEDVARVA MRLWSRSDIGLVGNHID VLTGKWVAQDAGIGAGVDSYFEYLVKGAILLQDKKLMAMFLEYNKAIRNYTRFDDWYLWVQMYKGTVSMPVF QLEAYWPGLQ The first amino acid sequence which is at least 90% homologous to R38144_PEA_2_P13, a sequence corresponding to the amino acids 324 to 341 of the amino acids R38144_PEA_2_P13, comprising a second amino acid sequence which is at least 90%, most preferably at least 95% homologous, said first amino acid sequence and the second amino acid sequence being adjacent and in sequential order It provides isolated chimeric polypeptides that over de.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of R38144_PEA_2_P13, which is at least 70%, optionally at least about 80%, preferably at least about 85%, with the sequence NLLKAQCTSTVPPRGIPPS in R38144_PEA_2_P13 More preferably, provided is an isolated polypeptide encoding the tail of R38144_PEA_2_P13, comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding R38144_PEA_2_P15, corresponding to amino acids 1-282 of CT31_HUMAN, corresponding to amino acids 1-282 of R38144_PEA_2_P15 MPFRLLIPLGLLCALLPQHHGAPGPDGSAPDPAHYRERVKAMFYHAYDSYLENAFPFDELRPLTCDGHDTWGSFSLTLIDALDTLLILGNVSEFQRVVEVLQDSVDFDIDVNASVFETNIRVVGGLLSAHLLSKKAGVEVEAGWPCSGPLLRMAEEAARKLLPAFQTPTGMPYGTVNLLHGVNPGETPVTCTAGIGTFIVEFATLSSLTGDPVFEDVARVA MRLWESSDIGLVGNHID VLT GKWVAQDAGIGAGVDSYFEYLVKGAILLQDKKLMAMFLE The first amino acid sequence at least 90% homologous to the polypeptide having the sequence PHWRH corresponding to amino acids 283-287 of R38144_PEA_2_P15, at least 70%, optionally at least 80%, preferably at least 85%, more preferably Comprises R38144_PEA_2_P15, which comprises a second amino acid sequence which is at least 90%, most preferably at least 95% homologous, said first amino acid sequence and the second amino acid sequence being adjacent and in sequential order An isolated chimeric polypeptide is provided.

  According to a preferred embodiment of the invention, an isolated polypeptide encoding the tail of R38144_PEA_2_P15, comprising at least 70%, optionally at least about 80%, preferably at least about 85%, of the sequence PHWRH in R38144_PEA_2_P15 More preferably, provided is an isolated polypeptide encoding the tail of R38144_PEA_2_P15, comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding R38144_PEA_2_P19, corresponding to amino acids 1-412 of CT31_HUMAN, corresponding to amino acids 1-412 of R38144_PEA_2_P19 MPFRLLIPLGLLCALLPQHHGAPGPDGSAPDPAHYRERVKAMFYHAYDSYLENAFPFDELRPLTCDGHDTWGSFSLTLIDALDTLLILGNVSEFQRVVEVLQDSVDFDIDVNASVFETNIRVVGGLLSAHLLSKKAGVEVEAGWPCSGPLLRMAEEAARKLLPAFQTPTGMPYGTVNLLHGVNPGETPVTCTAGIGTFIVEFATLSSLTGDPVFEDVARVA A first amino acid sequence at least 90% homologous to EmuaruerudaburyuiesuaruesudiaijierubuijienueichiaidibuierutijikeidaburyubuieikyudieijiaijieijibuidiesuwaiefuiwaierubuikeijieiaieruerukyudikeikeieruemueiemuefueruiwaienukeieiaiaruenuwaitiaruefudididaburyuwaierudaburyubuikyuemuwaikeijitibuiesuemuPibuiefukyuesueruieiwaidaburyuPijierukyuesueruaijidiaidienueiemuarutiefueruenuwaiwaitibuidaburyukeikyuefujijieruPiiefuwaienuaiPikyujiwaitibuiikeiaruijiwaiPieruaruPiieruaiiesueiemuwaieruwaiarueitijidipiTLLELGRDAVESIEKISKVECGFAT, polypeptide at least 70% with a sequence corresponding to KRSRSVAQAGVQWCDHDSPQP to amino acid 413-433 of R38144_PEA_2_P19, optionally at least 80%, preferably at least 85%, more Preferably at least 90 An isolated chimeric poly encoding R38144_PEA_2_P19, comprising a second amino acid sequence which is most preferably at least 95% homologous, said first amino acid sequence and the second amino acid sequence being adjacent and in sequential order Provide a peptide.

  According to a preferred embodiment of the invention, an isolated polypeptide encoding the tail of R38144_PEA_2_P19, which is at least 70%, optionally at least about 80%, preferably at least about 85%, with the sequence KRSRSVAQAGVQWCDHDSPQ in R38144_PEA_2_P19. More preferably, provided is an isolated polypeptide encoding the tail of R38144_PEA_2_P19, comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, the isolated chimeric polypeptide encoding R38144_PEA_2_P24, which corresponds to amino acids 1 to 121 of CT31_HUMAN and also to amino acids 1 to 121 of R38144 _PEA_2 _P24, is MPFRLLIPLGLLCALLPQHHGAPGPDGPHPHYPRKKAMFYHAYDSIFEN FIF LPDIGTITBIT GIT GIT GIT GIT First amino acid sequence and sequence corresponding to amino acids 282 to 578 of CT31_HUMAN EYNKAIRNYTRFDDWYLWVQMYKGTVSMPVFQSLEAYWPGLQSLIGDI NAMRTFLNYYTVWKQFGGLPEFYNIPQGYTVEKREGYPLRPELIESAMYLYRATGDPTLLELGRDAVESIEKISKVECGFATIKDLRDHKLDNRMESFFLAETVKYLYLLFDPTNFIHNNGSTFDAVITPYGECILGAGGYIFNTEAHPIDPAALHCCQRLKEEQWEVEDLMREFYSLKRSRSKFQKNTVSSGPWEPPARPGTLFSPENHDQARERKPAKQKVPLLSCPSQPFTSKLALLGQVFLDSS and and at least 90% homologous to a second amino acid sequence, the first amino acid sequence and a second amino acid sequence is in the order in which adjacent and contiguous, the R38144_PEA_2_P24 It provides isolated chimeric polypeptides that over de.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding the rim portion of R38144_PEA_2_P24, having a length “n”, wherein n is at least about 10 amino acids long, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length, most preferably at least about 50 amino acids in length), wherein at least two amino acids comprise RE; A polypeptide having a sequence beginning with any of the numbers 121-x to 121 and ending with the amino acid number 122 + ((n-2) -x), wherein x varies from 0 to n-2. Provided is an isolated chimeric polypeptide encoding the edge portion of R38144_PEA_2_P24, including:

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding R38144_PEA_2_P36, which corresponds to amino acids 1 to 36 of AAH 16184 and also to amino acids 1 to 36 of R38144_PEA 2 _P36 is at least 90% homologous to MPFRLLIPLGLLCALLPQHHGAPGPDGSAPDPAHYR At least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably a polypeptide having the first amino acid sequence and the sequence FWGMSQNSKEWLKCSRTAWTLILM corresponding to amino acids 37-60 of R38144_PEA_2_P36 Comprises a second amino acid sequence which is at least 95% homologous, said first amino acid sequence Beauty second amino acid sequence, contiguous and in sequential order, provides an isolated chimeric polypeptide coding R38144_PEA_2_P36.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of R38144_PEA_2_P36, which is at least 70%, optionally at least about 80%, preferably at least about 85%, with the sequence FWGMSQNSKEWLCCTTAWTLILM in R38144_PEA_2_P36 More preferably, provided is an isolated polypeptide encoding the tail of R38144_PEA_2_P36, comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, it is an isolated chimeric polypeptide encoding R38144_PEA_2_P36, which is at least 90% homologous to MPFRLLIPLGLLCALLPQHHGAPGPDGSAPDPAHY which corresponds to amino acids 1 to 35 of AAQ 88943 and also to amino acids 1 to 35 of R38144_PEA_2_P36. At least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably a polypeptide having the first amino acid sequence and the sequence RFWGMSQNSKEWLKCSRTAWTLILM corresponding to amino acids 36 to 60 of R38144_PEA_2_P36 Comprises a second amino acid sequence which is at least 95% homologous, said first amino acid sequence Beauty second amino acid sequence, contiguous and in sequential order, provides an isolated chimeric polypeptide coding R38144_PEA_2_P36.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of R38144_PEA_2_P36, comprising at least 70%, optionally at least about 80%, preferably at least about 85%, of the sequence RFWGMSQ NSKEWLCKCSRTAWTLILM in R38144_PEA_2_P36 More preferably, provided is an isolated polypeptide encoding the tail of R38144_PEA_2_P36, comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, it is an isolated chimeric polypeptide encoding R38144_PEA_2_P36, which is at least 90% homologous to MPFRLLIPLGLLCALLPQHHGAPGPDGSAPDPAHYR which corresponds to amino acids 1 to 36 of CT31_HUMAN and also to amino acids 1 to 36 of R38144_PEA_2_P36. At least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably a polypeptide having the first amino acid sequence and the sequence FWGMSQNSKEWLKCSRTAWTLILM corresponding to amino acids 37-60 of R38144_PEA_2_P36 Comprises a second amino acid sequence which is at least 95% homologous, said first amino acid sequence And a second amino acid sequence, contiguous and in sequential order, provides an isolated chimeric polypeptide coding R38144_PEA_2_P36.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of R38144_PEA_2_P36, which is at least 70%, optionally at least about 80%, preferably at least about 85%, with the sequence FWGMSQNSKEWLCCTTAWTLILM in R38144_PEA_2_P36 More preferably, provided is an isolated polypeptide encoding the tail of R38144_PEA_2_P36, comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding AA161187_P6, comprising at least 70%, optionally at least 80%, preferably at least 85% HTREGTLGGQKRAFPDGVEGEKGRGRAW assgsaVPLTIR corresponding to amino acids 1-42 of AA161187_P6. %, More preferably at least 90%, most preferably at least 95% corresponding to the first amino acid sequence homologous and at least 95% homologous to amino acids 31 to 314 of TEST_HUMAN and also to amino acids 43 to 326 of AA161187_P6 WSLQAYYTRYFVSNIYLSPRYLGNSPYDIALVKLSAPVTYTKHIQPICLQASTFEFENRTDCWVTGWGYIKEDEALPSPHTLQEVQVAIINNSMCNHLFLKYSFRKDIFGDMVCAGNAQGGKDACFGDSGGPLACNKNGLWYQIGVVSWGVGCGRPNRPGVYTNISHHFEWIQKLMAQSGMSQPDPSWPLLFFPLLWALPLLGPV and and at least 90% homologous to a second amino acid sequence, the first amino acid sequence and a second amino acid sequence, contiguous and in sequential order, the isolated chimeric polypeptide encoding AA161187_P6 I will provide a.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tip of AA161187_P6, comprising at least 70%, optionally at least about 80%, preferably at least about 85%, of the sequence HTREGTLGGQKRAFPDGVEVEGEKGRGRAWGAASRGSAVPLTIR of the AA161187_P6 Provided is an isolated polypeptide encoding the tip of AA161187_P6, which comprises a polypeptide that is preferably at least about 90%, and most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding a JIT, which corresponds to amino acids 1 to 183 of AA_116187_P13 and corresponds to A1 to 183 amino acids of AA161187_P13, also corresponds to A1 to 183 amino acids of AA161187_P13. First amino acid sequence, amino acids 184 to 21 of AA161187_P13 And a second amino acid sequence that is at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous to the polypeptide having the sequence GSSGRHHKQLYVQPPLPQVQFPQGHLWRHG The present invention provides an isolated chimeric polypeptide encoding AA161187_P13, wherein said first amino acid sequence and said second amino acid sequence are adjacent and in sequential order.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of AA161187_P13, which is at least 70%, optionally at least about 80%, preferably at least about 85%, with the sequence GSSGRHHKQLYVQPPLPQVQFPQGHLWRHG in AA161187_P13 More preferably, an isolated polypeptide encoding the tail of AA161187_P13, comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, the isolated chimeric polypeptide encoding JIT is a JIG, which corresponds to amino acids 1 to 183 of AA_116187_PHAN and corresponds to A1 to 183 amino acids of AA161187_PHAN. First amino acid sequence and amino acids 184 to 30 of AA161187_P14 The corresponding GCC LSP SHPH P STAH STA I P H S G P R GH Q Q LP Q Q FP Q GH L W RH H GL CW Q C REG C L H CH C Q P PK ASC VP VP LLT LTP TP G G D CC T Q MQEDR HP G C P Q at least 80%, optionally at least 80%, preferably at least 85%. Provided is an isolated chimeric polypeptide encoding AA161187_P14, wherein said first amino acid sequence and said second amino acid sequence are adjacent and in sequential order.

  According to a preferred embodiment of the present invention, the isolated polypeptide encoding the tail of AA161187_P14, which is the tail of AA161187_P14, and which is in the sequence of More preferably, an isolated polypeptide encoding the tail of AA161187_P14, comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding AA161187_P18, comprising at least 70%, optionally at least 80% of the polypeptide having the sequence HTREGTLGGQKRAFPDGVEGEGEGRGAASRGSAVPLTIR corresponding to amino acids 1-42 of AA161187_P18 GPCGRRVTISRIVGGEDAELGRWPWQGSLLRWDSHVCGVSLLSHRWALTAAHCFET, corresponding to a first amino acid sequence, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous and corresponding to amino acids 31 to 86 of TEST_HUMAN and also to amino acids 43 to 98 of AA161187_P18 And at least 90% DLDPDSGWMVQFGQLTSMPSFLSQA YET, corresponding to amino acids 89 to 235 of the TEST_HUMAN and corresponding to amino acids 99-245 of the AA161187_P18, is equivalent to amino acids 89 to 235 of the TEST_HUMAN, and also corresponds to At least 70%, optionally at least 80%, preferably less, with a polypeptide having the corresponding sequence VSVPATTSPSGKHPVSL CLI Said first amino acid sequence, the second amino acid sequence, the third amino acid sequence, and the fourth amino acid sequence also comprising 85%, more preferably at least 90%, most preferably at least 95% homologous fourth amino acid sequence; The present invention provides an isolated chimeric polypeptide encoding AA161187_P18, wherein the amino acid sequences of SEQ ID NO: are in a contiguous and sequential order.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tip of AA161187_P18, comprising at least 70%, optionally at least about 80%, preferably at least about 85%, of the sequence HTREGTLGGQKRAFPDGVEGEGEGRGAGASRGSAVPLTIR of the AA161187_P18 Provided is an isolated polypeptide encoding the tip of AA161187_P18, which comprises a polypeptide that is preferably at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding the rim portion of AA161187_P18, having a length "n", wherein n is at least about 10 amino acids long, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length, most preferably at least about 50 amino acids in length), wherein at least two amino acids comprise TD and have the following structure: A polypeptide having a sequence beginning with any of the numbers 98-x to 99 and ending with the amino acid number 99 + ((n-2) -x), wherein x varies from 0 to n-2. Provided is an isolated chimeric polypeptide encoding the edge portion of AA161187_P18, including.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of AA161187_P18, comprising at least 70%, optionally at least about 80%, preferably at least about 85% of the sequence VSVPATTPSPGKHPVSLCLI in AA161187_P18. Provided is an isolated polypeptide encoding the tail of AA161187_P18, more preferably comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, the isolated chimeric polypeptide encoding JIT is a JIG, which corresponds to amino acids 1 to 183 of AA_116187_PHAN and also corresponds to amino acids 1 to 183 of AA_161187_PHAN. First amino acid sequence, amino acids 184 to 18 of AA161187_P19 And a second amino acid sequence which is at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous to the polypeptide having the sequence DKRTQ corresponding to Provided is an isolated chimeric polypeptide encoding AA161187_P19, wherein said first amino acid sequence and said second amino acid sequence are adjacent and in sequential order.

  According to a preferred embodiment of the invention, an isolated polypeptide encoding the tail of AA161187_P19, comprising at least 70%, optionally at least about 80%, preferably at least about 85%, of the sequence DKRTQ in AA161187_P19. More preferably, an isolated polypeptide encoding the tail of AA161187_P19, comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, the isolated chimeric polypeptide encoding Z25299_PEA_2_P2, which corresponds to amino acids 1 to 131 of ALK1_HUMAN and also corresponds to amino acids 1 to 131 of Z25299_PEA_2_P2, is MKSSGLFPFLVL LGLTBWEGSQGPLYQPEQGTIJGTCIT GIGTI At least 70%, optionally less, with a polypeptide having the first amino acid sequence and the sequence GKQGMRAH corresponding to amino acids 132-139 of Z25299_PEA_2_P2 Comprising at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95%, of a second amino acid sequence homologous, said first and second amino acid sequences being adjacent and Provided is an isolated chimeric polypeptide encoding Z25299_PEA_2_P2 in sequential order.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of Z25299_PEA_2_P2, comprising at least 70%, optionally at least about 80%, preferably at least about 85% of the sequence GKQGMRAH in Z25299_PEA_2_P2 More preferably, provided is an isolated polypeptide encoding the tail of Z25299_PEA_2_P2 comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, the isolated chimeric polypeptide encoding Z25299_PEA_2_P3, which corresponds to amino acids 1 to 131 of ALK1_HUMAN and also corresponds to amino acids 1 to 131 of Z25299_PEA_2_P3. Polypeptide having a first amino acid sequence and the sequence GEKRHHKQLRDQEVDPLEMRHSAG corresponding to amino acids 132 to 156 of Z25299_PEA_2_P3 Said first and second amino acids comprising a second amino acid sequence which is at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous Provided is an isolated chimeric polypeptide encoding Z25299_PEA_2_P3 in a contiguous and sequential order.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of Z25299_PEA_2_P3, which is at least 70%, optionally at least about 80%, preferably at least about 85%, with the sequence GEKRHHKQLRDRDEVEVPLPMLRHSAG in Z25299_PEA_2_P3 More preferably, provided is an isolated polypeptide encoding the tail of Z25299_PEA_2_P3 comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding Z25299_PEA_2_P7, which corresponds to amino acids 1 to 81 of ALK1_HUMAN and also to amino acids 1 to 81 of Z25299_PEA_2_P7. The polypeptide having the sequence RGSLGSAQ corresponding to amino acids 82-89 of the first amino acid sequence and Z25299_PEA_2_P7 and at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably Is at least 95% phase And a second amino acid sequence, wherein the first and second amino acid distribution is contiguous, and in sequential order, provides an isolated chimeric polypeptide coding Z25299_PEA_2_P7.

  According to a preferred embodiment of the invention, an isolated polypeptide encoding the tail of Z25299_PEA_2_P7, comprising at least 70%, optionally at least about 80%, preferably at least about 85% of the sequence RGSLGSAQ in Z25299_PEA_2_P7. More preferably, provided is an isolated polypeptide encoding the tail of Z25299_PEA_2_P7, comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding Z25299_PEA_2_P10, corresponding to amino acids 1 to 82 of ALK1_HUMAN and also corresponding to amino acids 1 to 82 of Z25299_PEA_2_P10, Provided is an isolated chimeric polypeptide encoding Z25299_PEA_2_P10, comprising a first amino acid sequence.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding R66178_P3, corresponding to amino acids 1-334 of PVR1_HUMAN, corresponding to amino acids 1-334 of R66178_P3 MARMGLAGAAGRWWGLALGLTAFFLPGVHSQVVQVNDSMYGFIGTDVVLHCSFANPLPSVKITQVTWQKSTNGSKQNVAIYNPSMGVSVLAPYRERVEFLRPSFTDGTIRLSRLELEDEGVYICEFATFPTGNRESQLNLTVMAKPTNWIEGTQAVLRAKKGQDDKVLVATCTSANGKPPSVVSWETRLKGEAEYQEIRNPNGTVTVISRYRLVPSREAHQQSLACIVNYHMDRF ESLTLNVQYEPEVTIEGFDGNWYLQRMDV KLTKADANPPATEYHWTTLSLP SKGKGVEAQNRTLFFKGPINYSLAG ITIC ETITGIGS SGQVNVIT The first amino acid sequence which is at least 90% homologous to the amino acid 335-354 of R66178_P3. Comprises a second amino acid sequence which is at least 90%, most preferably at least 95% homologous, the first amino acid sequence and the second amino acid sequence encoding R66178_P3, adjacent and in sequential order Isolated chimeric polypeptide To provide.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of R66178_P3 and at least 70%, optionally at least about 80%, preferably at least about 85%, with the sequence GEGHSLPISPGVLQTQNCGP in R66178_P3. Provided is an isolated polypeptide encoding the tail of R66178_P3, more preferably comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding R66178_P4, corresponding to amino acids 1-334 of PVR1_HUMAN, corresponding to amino acids 1-334 of R66178_P4 MARMGLAGAAGRWWGLALGLTAFFLPGVHSQVVQVNDSMYGFIGTDVVLHCSFANPLPSVKITQVTWQKSTNGSKQNVAIYNPSMGVSVLAPYRERVEFLRPSFTDGTIRLSRLELEDEGVYICEFATFPTGNRESQLNLTVMAKPTNWIEGTQAVLRAKKGQDDKVLVATCTSANGKPPSVVSWETRLKGEAEYQEIRNPNGTVTVISRYRLVPSREAHQQSLACIVNYHMDRF ESLTLNVQYEPEVTIEGFDGNWYLQRMDV KLTCKADANPPATEYHWTTLSLP SKGKGVEAQNRTLFFKPINYSLAG ITIC ETITGIGSGVEVNIT The first amino acid sequence which is at least 90% homologous to the amino acid 335-352 of R66178_P4. Comprises a second amino acid sequence that is at least 90%, most preferably at least 95% homologous, the first amino acid sequence and the second amino acid sequence encoding R66178_P4, adjacent and in sequential order Isolated chimeric polypeptide Subjected to.

  According to a preferred embodiment of the invention, an isolated polypeptide encoding the tail of R66178_P4, comprising at least 70%, optionally at least about 80%, preferably at least about 85%, of the sequence AFCQLIYPGKGRTRARMF in R66178_P4. Provided is an isolated polypeptide encoding the tail of R66178_P4, more preferably comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding R66178_P8, corresponding to amino acids 1-330 of PVR1_HUMAN, corresponding to amino acids 1-330 of R66178_P8 MARMGLAGAAGRWWGLALGLTAFFLPGVHSQVVQVNDSMYGFIGTDVVLHCSFANPLPSVKITQVTWQKSTNGSKQNVAIYNPSMGVSVLAPYRERVEFLRPSFTDGTIRLSRLELEDEGVYICEFATFPTGNRESQLNLTVMAKPTNWIEGTQAVLRAKKGQDDKVLVATCTSANGKPPSVVSWETRLKGEAEYQEIRNPNGTVTVISRYRLVPSREAHQQSLACIVNYHMDRF ESLTLNVQYEPEVTIEGFDGNWYLKTRMADANPPATEYHWT LSHSLPGKGVEAQNRTLFFKGPINYSLAG ITIC ETIIGTGSQQVE The first amino acid sequence which is at least 90% homologous to the amino acid 331 to 333 of R66178_P8 and the NSCTPRLNMGMGGRCPRPGAG Comprises R66178_P8, comprising a second amino acid sequence which is at least 90%, most preferably at least 95% homologous, said first amino acid sequence and the second amino acid sequence being adjacent and in a consecutive order single It provides a chimeric polypeptide.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of R66178_P8, which is at least 70%, optionally at least about 80%, preferably at least about 85%, with the sequence NSPTPRLLPNMGGAPGRCPRPSLGAWRGASCWC in R66178_P8. Provided is an isolated polypeptide encoding the tail of R66178_P8, which more preferably comprises a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding HSU33147_PEA_1_P5, which corresponds to amino acids 1 to 78 of MGBA_HUMAN and also to amino acids 1 to 78 of HSU33147_PEA_1_P5, is MKLLMVLMLAALSQ HC YAGGSGCPLLENVISKTINPQ VSKTEOKELL QEFIDDNATTN A first amino acid sequence, and a second amino acid sequence corresponding to amino acids 82 to 93 of MGBA_HUMAN and also corresponding to amino acids 79 to 90 of HSU33147_PEA_1_P5 and QLIYDSSLCDLF at least 90% homologous to the first amino acid sequence; The second amino acid sequence is Adjacent, and in sequential order, it provides an isolated chimeric polypeptide coding HSU33147_PEA_1_P5.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding the edge portion of HSU33147_PEA_1_P5, having a length “n”, where n is at least about 10 amino acids long, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length, most preferably at least about 50 amino acids in length), wherein at least two amino acids comprise EQ and have the following structure: A polypeptide having a sequence beginning with any of the numbers 78-x to 78 and ending with the amino acid number 79 + ((n-2) -x), wherein x varies from 0 to n-2. Provided is an isolated chimeric polypeptide encoding the edge portion of HSU33147_PEA_1_P5, including:

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding HSU33147_PEA_1_P5, which corresponds to amino acids 1 to 78 of MGBA_HUMAN and also to amino acids 1 to 78 of HSU33147_PEA_1_P5, is MKLLMVLMLAALSQ HC YAGGSGCPLLENVISKTINPQ VSKTEOKELL QEFIDDNATTN A first amino acid sequence, and a second amino acid sequence corresponding to amino acids 82 to 93 of MGBA_HUMAN and also corresponding to amino acids 79 to 90 of HSU33147_PEA_1_P5 and QLIYDSSLCDLF at least 90% homologous to the first amino acid sequence; The second amino acid sequence is Adjacent, and in sequential order, it provides an isolated chimeric polypeptide coding HSU33147_PEA_1_P5.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding the edge portion of HSU33147_PEA_1_P5, having a length “n”, where n is at least about 10 amino acids long, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length, most preferably at least about 50 amino acids in length), wherein at least two amino acids comprise EQ and have the following structure: A polypeptide having a sequence beginning with any of the numbers 78-x to 78 and ending with the amino acid number 79 + ((n-2) -x), wherein x varies from 0 to n-2. Provided is an isolated chimeric polypeptide encoding the edge portion of HSU33147_PEA_1_P5, including:

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding M78076_PEA_1_P3, corresponding to amino acids 1-517 of APP1_HUMAN, corresponding to amino acids 1-517 of M78076_PEA_1_P3 MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGLCGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPMERWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCPPPGTPDPSGTAV A first amino acid sequence at least 90% homologous to DiPiesutiaruesudaburyuPiPijiesuarubuiijieiidiiiiiiesuefuPikyuPibuididiwaiefubuiiPiPikyueiiiiiitibuiPipipiesuesueichitierueibuibuijikeibuitiPitiPiaruPitidijibuidiaiwaiefujiemuPijiiaiesuieichiijiefueruarueikeiemudieruiiaruaruemuarukyuaienuibuiemuaruidaburyueiemueidienukyuesukeienueruPikeieidiarukyueieruenuieichiefukyuesuaierukyutieruiikyubuiesujiiarukyuaruerubuiitieichieitiarubuiaieieruaienudikyuaruarueieieruijiefuerueieierukyueidiPiPikyueiiarubuieruerueieruaruaruwaieruarueiikyukeiikyuarueichitieruarueichiwaikyueichibuieieibuidiPiikeieikyukyuemuaruefukyubuieichitieichierukyubuiaiiiarubuienukyuesuerujieruerudikyuenuPieichierueikyuieruaruPikyuaikyuieruerueichiesuieichieruJipiSELEAPAPGGSSEDKGGLQPPDSKD, the M78076_PEA_1_P3 A second, at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous to a polypeptide having the sequence GE corresponding to minonic acid 518-519. And an isolated chimeric polypeptide encoding M78076_PEA_1_P3 in which the first and second amino acid sequences are adjacent and in sequential order.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding M78076_PEA_1_P4, corresponding to amino acids 1-526 of APP1_HUMAN, corresponding to amino acids 1-526 of M78076_PEA_1_P4 MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGLCGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPMERWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCPPPGTPDPSGTAV The first amino acid sequence at least 90% homologous to DPSTRSWPPGSRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGKVTPTPRPTDGVDIYFGMPGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQALNEHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQADPPQAERVLLALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQVHTHLQVIEERVNQSLGLLDQNPHLAQELRPQIQELLHSEHLGPSELEAPAPGGSSEDKGGLQPPDSKDDTPMTLPKG, M78076_ A polypeptide having at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homology to the polypeptide having the sequence ECLTVNPSLQIPLNP corresponding to amino acids 527 to 541 of EA_1_P4 An isolated chimeric polypeptide encoding M78076_PEA_1_P4, comprising two amino acid sequences, wherein said first and second amino acid sequences are adjacent and in sequential order.

  According to a preferred embodiment of the invention, an isolated polypeptide encoding the tail of M78076_PEA_1_P4, comprising at least 70%, optionally at least about 80%, preferably at least about 85% of the sequence ECLTVNPSLQIPLNP in M78076_PEA_1_P4. More preferably, provided is an isolated polypeptide encoding the tail of M78076_PEA_1_P4, comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding M78076_PEA_1_P12, corresponding to amino acids 1-526 of APP1_HUMAN, corresponding to amino acids 1-526 of M78076_PEA_1_P12 MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGLCGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPMERWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCPPPGTPDPSGT The first amino acid sequence at least 90% homologous to VGDPSTRSWPPGSRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGKVTPTPRPTDGVDIYFGMPGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQALNEHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQADPPQAERVLLALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQVHTHLQVIEERVNQSLGLLDQNPHLAQELRPQIQELLHSEHLGPSELEAPAPGGSSEDKGGLQPPDSKDDTPMTLPKG, M7807 A polypeptide having the sequence ECVCSKGFPFPLIGDSEG corresponding to amino acids 527 to 544 of PEA_1_P12 at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous An isolated chimeric polypeptide encoding M78076_PEA_1_P12, comprising two amino acid sequences, wherein said first and second amino acid sequences are adjacent and in sequential order.

  According to a preferred embodiment of the invention, an isolated polypeptide encoding the tail of M78076_PEA_1_P12, comprising at least 70%, optionally at least about 80%, preferably at least about 85% of the sequence ECVCSKGFPFPLIGDSEG in M78076_PEA_1_P12. More preferably, provided is an isolated polypeptide encoding the tail of M78076_PEA_1_P12, comprising a polypeptide that is at least about 90%, and most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding M78076_PEA_1_P14, corresponding to amino acids 1-570 of APP1_HUMAN, corresponding to amino acids 1-570 of M78076_PEA_1_P14 MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGLCGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPMERWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCPPPGTPDPSGT VGDPSTRSWPPGSRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGKVTPTPRPTDGVDIYFGMPGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQALNEHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQADPPQAERVLLALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQVHTHLQVIEERVNQSLGLLDQNPHLAQELRPQIQELLHSEHLGPSELEAPAPGGSSEDKGGLQPPDSKDDTPMTLPKGSTEQDAASPEKEKMNPLEQYERKVNASV At least 70%, optionally at least 80%, preferably at least 85%, more preferably a first amino acid sequence at least 90% homologous to RGFPFHSEIQRDEL and a polypeptide having the sequence VRGGTAGYLGEETRGQQRPGCDSQSHTGPSKKPSAPSPLPAGTSWDRGVP corresponding to amino acids 571-619 of M78076_PEA_1_P14 Comprises M78076_PEA_1_P14, comprising a second amino acid sequence which is at least 90%, most preferably at least 95% homologous, said first and second amino acid sequences being adjacent and in sequential order An isolated chimeric polypeptide is provided.

  According to a preferred embodiment of the invention, an isolated polypeptide encoding the tail of M78076_PEA_1_P14, comprising at least 70%, optionally at least about 80%, preferably at least about 85% of the sequence VRGGTAGYLGEETRGQRPGCDCSQSHTGPSKKPSAPSPLPAGTSWDRGVP in M78076_PEA_1_P14 More preferably, provided is an isolated polypeptide encoding the tail of M78076_PEA_1_P14, comprising a polypeptide that is at least about 90%, and most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding M78076_PEA_1_P21, corresponding to amino acids 1-352 of APP1_HUMAN, corresponding to amino acids 1-352 of M78076_PEA_1_P21 MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGLCGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPMERWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCPPPGTPDPSGT The first amino acid sequence at least 90% homologous to BuijidiPiesutiaruesudaburyuPiPijiesuarubuiijieiidiiiiiiesuefuPikyuPibuididiwaiefubuiiPiPikyueiiiiiitibuiPipipiesuesueichitierueibuibuijikeibuitiPitiPiaruPitidijibuidiaiwaiefujiemuPijiiaiesuieichiijiefueruarueikeiemudieruiiaruaruemuarukyuaienuiVMREWAMADNQSKNLPKADRQALNE, corresponding to amino acids 406-650 of APP1_HUMAN, corresponding to amino acids 353-597 of M78076_PEA_1_P21 AERVLLALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQVHTHLQVIEERVNQSLGLLDQNPHLAQELRPQIQELLHSEHLGPSELEAPAPGGSSEDKGGLQPPDSKDDTPMTL A first amino acid sequence and a second amino acid sequence containing at least a 90% homology with a second amino acid sequence, and an N-terminal peptide chain, and provide.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding the rim portion of M78076_PEA_1_P21, having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length, most preferably at least about 50 amino acids in length), wherein at least two amino acids comprise EA; A polypeptide having a sequence beginning at any of the numbers 352-x to 352 and ending at the amino acid number 353 + ((n-2) -x), wherein x varies from 0 to n-2 Provided is an isolated chimeric polypeptide encoding an edge portion of M78076_PEA_1_P21, including:

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding M78076_PEA_1_P24, corresponding to amino acids 1-481 of APP1_HUMAN, corresponding to amino acids 1-481 of M78076_PEA_1_P24 MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGLCGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPMERWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCPPPGTPDPSGT The first amino acid sequence at least 90% homologous to BuijidiPiesutiaruesudaburyuPiPijiesuarubuiijieiidiiiiiiesuefuPikyuPibuididiwaiefubuiiPiPikyueiiiiiitibuiPipipiesuesueichitierueibuibuijikeibuitiPitiPiaruPitidijibuidiaiwaiefujiemuPijiiaiesuieichiijiefueruarueikeiemudieruiiaruaruemuarukyuaienuibuiemuaruidaburyueiemueidienukyuesukeienueruPikeieidiarukyueieruenuieichiefukyuesuaierukyutieruiikyubuiesujiiarukyuaruerubuiitieichieitiarubuiaieieruaienudikyuaruarueieieruijiefuerueieierukyueidiPiPikyueiiarubuieruerueieruaruaruwaieruarueiikyukeiikyuarueichitieruarueichiwaikyueichibuieieibuidiPiikeieikyukyuemuaruefukyubuieichitieichierukyubuiaiEERVNQSLGLLDQNPHLAQELRPQI, sequence RECLLPWLPLQISEG corresponding to amino acids 482-498 of M78076_PEA_1_P24 A polypeptide comprising S and a second amino acid sequence which is at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous; Provided is an isolated chimeric polypeptide encoding M78076_PEA_1_P24, wherein the amino acid sequence of 1 and the second amino acid sequence are adjacent and in sequential order.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of M78076_PEA_1_P24, comprising at least 70%, optionally at least about 80%, preferably at least about 85% of the sequence RECLLPWLPLQISEGRS in M78076_PEA_1_P24. More preferably, provided is an isolated polypeptide encoding the tail of M78076_PEA_1_P24, comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding M78076_PEA_1_P2, corresponding to amino acids 1-449 of APP1_HUMAN, corresponding to amino acids 1-449 of M78076_PEA_1_P2 MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGLCGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPMERWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCPPPGTPDPSGTAV The first amino acid sequence at least 90% homologous to DiPiesutiaruesudaburyuPiPijiesuarubuiijieiidiiiiiiesuefuPikyuPibuididiwaiefubuiiPiPikyueiiiiiitibuiPipipiesuesueichitierueibuibuijikeibuitiPitiPiaruPitidijibuidiaiwaiefujiemuPijiiaiesuieichiijiefueruarueikeiemudieruiiaruaruemuarukyuaienuibuiemuaruidaburyueiemueidienukyuesukeienueruPikeieidiarukyueieruenuieichiefukyuesuaierukyutieruiikyubuiesujiiarukyuaruerubuiitieichieitiarubuiaieieruaienudikyuaruarueieieruijiefuerueieierukyueidiPiPikyueiiarubuieruerueieruaruaruwaieruarueiikyukeiikyuRHTLRHYQHVAAVDPEKAQQMRFQV, sequence LTSFQLPNAPLFLRRPRLRLFSCPLDPLSVSWTPSYPLNTASLPLPSLSA corresponding to amino acids 450-588 of M78076_PEA_1_P2 LPDPETWTLTCCVFDPCFLALGF LLPLPPPSILSCPWIFTAFPRIVFFFFFFLRQVLALSPRQESSVRSWLIATSTSWVQAILLPQPLE and containing a second amino acid sequence at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous to the second amino acid sequence; Provided is an isolated chimeric polypeptide encoding M78076_PEA_1_P2 in which the amino acid sequence of 1 and the second amino acid sequence are adjacent and in sequential order.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of M78076_PEA_1_P2 comprising the following in the sequence L78076_PEA_1_P2: More preferably, an isolated polypeptide encoding the tail of M78076_PEA_1_P2 comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous To provide.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding M78076_PEA_1_P25, corresponding to amino acids 1-448 of APP1_HUMAN, corresponding to amino acids 1-448 of M78076_PEA_1_P25 MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGLCGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPMERWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCPPPGTPDPSGT The first amino acid sequence at least 90% homologous to BuijidiPiesutiaruesudaburyuPiPijiesuarubuiijieiidiiiiiiesuefuPikyuPibuididiwaiefubuiiPiPikyueiiiiiitibuiPipipiesuesueichitierueibuibuijikeibuitiPitiPiaruPitidijibuidiaiwaiefujiemuPijiiaiesuieichiijiefueruarueikeiemudieruiiaruaruemuarukyuaienuibuiemuaruidaburyueiemueidienukyuesukeienueruPikeieidiarukyueieruenuieichiefukyuesuaierukyutieruiikyubuiesujiiarukyuaruerubuiitieichieitiarubuiaieieruaienudikyuaruarueieieruijiefuerueieierukyueidiPiPikyueiiarubuieruerueieruaruaruwaieruarueiikyukeiiQRHTLRHYQHVAAVDPEKAQQMRFQ, sequence PQNPNSQPRAAGSLEVIISHPFVRRLEILISPFQFQNSIPKNSQIVPA corresponding to amino acids 449-505 of M78076_PEA_1_P25 Said polypeptide comprising a polypeptide having SPRGTSSP and a second amino acid sequence which is at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous; Provided is an isolated chimeric polypeptide encoding M78076_PEA_1_P25, wherein the amino acid sequence of 1 and the second amino acid sequence are adjacent and in sequential order.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of M78076_PEA_1_P25, comprising at least 70%, optionally at least about 80%, preferably at least about 85%, of the sequence PQNNPSTQPRAAGSLEVIISHPFVRRLEILISPFQFQNSIPKNSQIVPAASPRTSSP in M78076_PEA_1_P25 More preferably, provided is an isolated polypeptide encoding the tail of M78076_PEA_1_P25, comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding M79217_PEA_1_P1, corresponds to amino acids 13-931 of BAA25445, corresponding to amino acids 1-919 of M79217_PEA_1_P1 MTGYTMLRNGGAGNGGQTCMLRWSNRIRLTWLSFTLFVILVFFPLIAHYYLTTLDEADEAGKRIFGPRVGNELCEVKHVLDLCRIRESVSEELLQLEAKRQELNSEIAKLNLKIEACKKSIENAKQDLLQLKNVISQTEHSYKELMAQNQPKLSLPIRLLPEKDDAGLPPPKATRGCRLHNCFDYSRCPLTSGFPVYVYDSDQFVFGSYLDPLVKQAFQATARA VYVTENADIACLYVILVGEMQEPVVLRPAELEKQLYSLPHWRTDGHNHVIINLSRKSDTQNLLYNVSTGRAMVAQSTFYTVQYRPGFDLVVSPLVHAMSEPNFMEIPPQVPVKRKYLFTFQGEKIESLRSSLQEARSFEEEMEGDPPADYDDRIIATLKAVQDSKLDQVLVEFTCKNQPKPSLPTEWALCGEREDRLELLKLSTFALIITPGDPRLVISSGCATRLFEALEVGAVPVVLGEQVQLPYQDMLQWNEAALVVPKPRVTEVHFLLRSLSDSDLLAMRRQGRFLWETYFSTADSIFNTVLAMIRTRIQIPAAPIREEAAAEIPHRS KAAGTDPNMADNGDLDLGPVETEPPYASPRYLRNFTLTVTDFYRSWNCAPGPFHLFPHTPFDPVLPSEAKFLGSGTGFRPIGGGAGGSGKEFQAALGGNVPREQFTVVMLTYEREEVLMNSLERLNGLPYLNKVVVVWNSPKLPSEDLLWPDIGVPIMVVRTEKNSLNNRFLPWNEIETEAILSIDDDAHLRHDEIMFGFRVWREARDRIVGFPGRYHAWDIPHQSWLYNSNYSCELSMVLTGAAFFHKYYAYLYSYVMPQAIRDMVDEYINCEDIAMNFLVSHITRKPPIKVTSRWTFRCPGCPQALSHDDSHFHERHKCINFFVKVYGYMP Provided is an isolated chimeric polypeptide encoding M79217_PEA_1_P1, comprising a first amino acid sequence that is at least 90% homologous to LLYTQFRVDSVLFKTRLPHDKTKCFKFI.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding M79217_PEA_1_P2, corresponding to amino acids 1-807 of EXL3_HUMAN, corresponding to amino acids 1-807 of M79217_PEA_1_P2 MTGYTMLRNGGAGNGGQTCMLRWSNRIRLTWLSFTLFVILVFFPLIAHYYLTTLDEADEAGKRIFGPRVGNELCEVKHVLDLCRIRESVSEELLQLEAKRQELNSEIAKLNLKIEACKKSIENAKQDLLQLKNVISQTEHSYKELMAQNQPKLSLPIRLLPEKDDAGLPPPKATRGCRLHNCFDYSRCPLTSGFPVYVYDSDQFVFGSYLDPLVKQAFQATAR NVYVTENADIACLYVILVGEMQEPVVLRPAELEKQLYSLPHWRTDGHNHVIINLSRKSDTQNLLYNVSTGRAMVAQSTFYTVQYRPGFDLVVSPLVHAMSEPNFMEIPPQVPVKRKYLFTFQGEKIESLRSSLQEARSFEEEMEGDPPADYDDRIIATLKAVQDSKLDQVLVEFTCKNQPKPSLPTEWALCGEREDRLELLKLSTFALIITPGDPRLVISSGCATRLFEALEVGAVPVVLGEQVQLPYQDMLQWNEAALVVPKPRVTEVHFLLRSLSDSDLLAMRRQGRFLWETYFSTADSIFNTVLAMIRTRIQIPAAPIREEAAAEIPHR The first amino acid sequence at least 90% homologous to JikeieieijitidiPienuemueidienujidierudieruJipibuiitiiPiPiwaiEiesupiaruwaieruaruenuefutierutibuitidiefuwaiaruesudaburyuenushieiPiJipiefueichieruefuPieichitiPiefudiPibuieruPiesuieikeiefuerujiesujitijiefuaruPiaijijijieijijiesujikeiiefukyueieierujijienubuiPiaruikyuefutibuibuiemuerutiwaiiaruiibuieruemuenuesueruiarueruenujieruPiwaieruenukeibuibuibuibuidaburyuenuesuPikeieruPiesuidieruerudaburyuPidiaijibuiPiaiemubuibuiarutiikeienuesueruenuenuaruefueruPidaburyuenuiaiitiieiaieruesuaidididieieichieruarueichidiiaiemuefujiefuarubuidaburyuaruieiarudiaruaibuijiefuPijiaruwaieichieidaburyudiaipehaQSWLYNSNYSCELSMVLTGAAFFHK, corresponding to amino acids 820-919 of EXL3_HUMAN, corresponding to amino acids 808-907 of M79217_PEA_1_P2 A second amino acid sequence that is at least 90% homologous to the second amino acid sequence and at least 90% homologous to the second amino acid sequence, and the first and second amino acid sequences are adjacent and continuous. provide.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding the edge portion of M79217_PEA_1_P2, having a length “n”, where n is at least about 10 amino acids long, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length, most preferably at least about 50 amino acids in length), wherein at least two amino acids comprise KA and have the following structure: A polypeptide having a sequence beginning with any of the numbers 807-x to 807 and ending at the amino acid number 808 + ((n-2) -x), where x varies from 0 to n-2. Provided is an isolated chimeric polypeptide encoding the edge portion of M79217_PEA_1_P2, including:

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding M79217_PEA_1_P4, comprising at least 70%, optionally at least 80%, of a polypeptide having the sequence PELRQPARLGPECWDWDHERHEPRCPAQMGSHFIVQLAGLSK SK PK PKCWDY corresponding to amino acids 1 to 51 of M79217_PEA_1_P4 RVWREARDRIVGFPGRYHAWDIPHQSWLYNSNYSCELSMVLTGA corresponding to the first amino acid sequence, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous and corresponding to amino acids 759 to 919 of EXL3_HUMAN and also to amino acids 52 to 212 of M79217_PEA_1_P4 FFHKYYALYLYSYVMPQAIRDMVDEYINCDIAMNFLVSHITRKPPIKVTSRWTFRCPGQALSHDDSHHFHERHKCINFFVKVYVYPGYMLYTQFRVDSVLFKTRLPHDKTKKKFI containing a second amino acid sequence and at least one of the first and second amino acid sequences, and the corresponding ones, and the corresponding ones provide.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tip of M79217_PEA_1_P4, comprising at least 70%, optionally at least about 80%, preferably at least about 85%, of the sequence PELRQPARLGPLECPEDW Provided is an isolated polypeptide encoding the tip of M79217_PEA_1_P4, which preferably comprises a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding M79217_PEA_1_P8, corresponding to amino acids 1-807 of EXL3_HUMAN, corresponding to amino acids 1-807 of M79217_PEA_1_P8 MTGYTMLRNGGAGNGGQTCMLRWSNRIRLTWLSFTLFVILVFFPLIAHYYLTTLDEADEAGKRIFGPRVGNELCEVKHVLDLCRIRESVSEELLQLEAKRQELNSEIAKLNLKIEACKKSIENAKQDLLQLKNVISQTEHSYKELMAQNQPKLSLPIRLLPEKDDAGLPPPKATRGCRLHNCFDYSRCPLTSGFPVYVYDSDQFVFGSYLDPLVKQAFQATAR NVYVTENADIACLYVILVGEMQEPVVLRPAELEKQLYSLPHWRTDGHNHVIINLSRKSDTQNLLYNVSTGRAMVAQSTFYTVQYRPGFDLVVSPLVHAMSEPNFMEIPPQVPVKRKYLFTFQGEKIESLRSSLQEARSFEEEMEGDPPADYDDRIIATLKAVQDSKLDQVLVEFTCKNQPKPSLPTEWALCGEREDRLELLKLSTFALIITPGDPRLVISSGCATRLFEALEVGAVPVVLGEQVQLPYQDMLQWNEAALVVPKPRVTEVHFLLRSLSDSDLLAMRRQGRFLWETYFSTADSIFNTVLAMIRTRIQIPAAPIREEAAAEIPHR GKAAGTDPNMADNGDLDLGPVETEPPYASPRYLRNFTLTVTDFYRSWNCAPGPFHLFPHTPFDPVLPSEAKFLGSGTGFRPIGGGAGGSGKEFQAALGGNVPREQFTVVMLTYEREEVLMNSLERLNGLPYLNKVVVVWNSPKLPSEDLLWPDIGVPIMVVRTEKNSLNNRFLPWNEIETEAILSIDDDAHLRHDEIMFGFRVWREARDRIVGFPGRYHAWDIPHQSWLYNSNYSCELSMVLTGAAFFHK at least 90% homologous with the same a first amino acid sequence, a polypeptide at least 70% with a sequence corresponding to VRKSW to amino acid 808-812 of M79217_PEA_1_P8, Ren Said first amino acid sequence and said second amino acid sequence comprising a second amino acid sequence, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous. Provides an isolated chimeric polypeptide encoding M79217_PEA_1_P8, in contiguous and sequential order.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of M79217_PEA_1_P8, comprising at least 70%, optionally at least about 80%, preferably at least about 85%, of the sequence VRKSW in M79217_PEA_1_P8 More preferably, provided is an isolated polypeptide encoding the tail of M79217_PEA_1_P8, comprising a polypeptide that is at least about 90%, and most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding M62096_PEA_1_P4 comprising at least 70%, optionally at least 80% of a polypeptide having the sequence MATYIH corresponding to amino acids 1 to 6 of M62096_PEA_1_P4. VSKTGAEGLSNAGSLEKTHTHVP YRDSKMTRILQGLSGTIEGTICTITGITCITGITCITGIV VSVNLELTAEEWKKKYEKEKEKNKTLKNVIQHLEMELNRWRNGEAVPEDEQISAKDQKNLEPCDNTPIIDNIAPVVAGISTEEKEKYDEEISSLYRQLDDKDDEINQQSQLAEKLKQQMLDQDELLASTRRDYEKIQEELTRLQIENEAAKDEVKEVLQALEELAVNYDQKSQEVEDKTRANEQLTDELAQKTTTLTTTQRELSQLQELSNHQKKRATEILNLLLKDLGEIGGIIGTNDVKTLADVNGVIEEEFTMARLYISKMKSEVKSLVNRSKQLESAQMDSNRKMNASERELAACQLLISQHEAKIKSLTDYMQNMEQKRRQLEESQD LSEELAKLRAQEKMHEVSFQDKEKEHLTRLQDAEEMKKALEQQMESHREAHQKQLSRLRDEIEEKQKIIDEIRDLNQKLQLEQEKLSSDYNKLKIEDQEREMKLEKLLLLNDKREQAREDLKGLEETVSRELQTLHNLRKLFVQDLTTRVKKSVELDNDDGGGSAAQKQKISFLENNLEQLTKVHKQLVRDNADLRCELPKLEKRLRATAERVKALESALKEAKENAMRDRKRYQQEVDRIKEAVRAKNMARRAHSAQIAKPIRPGHYPASSPTAVHAIRGGGGSSSNSTHYQK and and at least 90% homologous to a second amino acid sequence, Oyo said first amino acid sequence The present invention provides an isolated chimeric polypeptide encoding M62096_PEA_1_P4, wherein the second amino acid sequence is in a contiguous and sequential order.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tip of M62096_PEA_1_P4, which is at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably with the sequence MATYIH of M62096_PEA_1_P4 Provided is an isolated polypeptide encoding the tip of M62096_PEA_1_P4, which preferably comprises a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding M62096_PEA_1_P5, corresponding to amino acids 284-957 of KF5C_HUMAN, corresponding to amino acids 1-674 of M62096_PEA_1_P5 MTRILQDSLGGNCRTTIVICCSPSVFNEAETKSTLMFGQRAKTIKNTVSVNLELTAEEWKKKYEKEKEKNKTLKNVIQHLEMELNRWRNGEAVPEDEQISAKDQKNLEPCDNTPIIDNIAPVVAGISTEEKEKYDEEISSLYRQLDDKDDEINQQSQLAEKLKQQMLDQDELLASTRRDYEKIQEELTRLQIENEAAKDEVKEVLQALEELAVNYDQKSQE EDKTRANEQLTDELAQKTTTLTTTQRELSQLQELSNHQKKRATEILNLLLKDLGEIGGIIGTNDVKTLADVNGVIEEEFTMARLYISKMKSEVKSLVNRSKQLESAQMDSNRKMNASERELAACQLLISQHEAKIKSLTDYMQNMEQKRRQLEESQDSLSEELAKLRAQEKMHEVSFQDKEKEHLTRLQDAEEMKKALEQQMESHREAHQKQLSRLRDEIEEKQKIIDEIRDLNQKLQLEQEKLSSDYNKLKIEDQEREMKLEKLLLLNDKREQAREDLKGLEETVSRELQTLHNLRKLFVQDLTTRVKKSVELDNDDGGGSAAQKQKISFL NNLEQLTKVHKQLVRDNADLRCELPKLEKRLRATAERVKALESALKEAKENAMRDRKRYQQEVDRIKEAVRAKNMARRAHSAQIAKPIRPGHYPASSPTAVHAIRGGGGSSSNSTHYQK and containing at least 90% homologous first amino acid sequence, provides an isolated chimeric polypeptide coding M62096_PEA_1_P5.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding M62096_PEA_1_P3, corresponding to amino acids 365-957 of KF5C_HUMAN, corresponding to amino acids 1-593 of M62096_PEA_1_P3 MELNRWRNGEAVPEDEQISAKDQKNLEPCDNTPIIDNIAPVVAGISTEEKEKYDEEISSLYRQLDDKDDEINQQSQLAEKLKQQMLDQDELLASTRRDYEKIQEELTRLQIENEAAKDEVKEVLQALEELAVNYDQKSQEVEDKTRANEQLTDELAQKTTTLTTTQRELSQLQELSNHQKKRATEILNLLLKDLGEIGGIIGTNDVKTLADVNGVIEEEFT ARLYISKMKSEVKSLVNRSKQLESAQMDSNRKMNASERELAACQLLISQHEAKIKSLTDYMQNMEQKRRQLEESQDSLSEELAKLRAQEKMHEVSFQDKEKEHLTRLQDAEEMKKALEQQMESHREAHQKQLSRLRDEIEEKQKIIDEIRDLNQKLQLEQEKLSSDYNKLKIEDQEREMKLEKLLLLNDKREQAREDLKGLEETVSRELQTLHNLRKLFVQDLTTRVKKSVELDNDDGGGSAAQKQKISFLENNLEQLTKVHKQLVRDNADLRCELPKLEKRLRATAERVKALESALKEAKENAMRDRKRYQQEVDRIKEAVRAKNMARRAH AQIAKPIRPGHYPASSPTAVHAIRGGGGSSSNSTHYQK and containing at least 90% homologous first amino acid sequence, provides an isolated chimeric polypeptide coding M62096_PEA_1_P3.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding M62096_PEA_1_P7, comprising a polypeptide having the sequence MTQNFRLMWNILLFPLNFS corresponding to amino acids 1-19 of M62096_PEA_1_P7, at least 70%, optionally at least 80% LNQKLQLEQELLSLL YDLKLELDLKLDL KLDAREGLKGLEETV SQ LQQ L And at least 90% at the end, it is at the same timing as the G77 and it is the N-SIP and the APIP) and it is the NIP API ... and the YTIP is the NIPIPIP ... which it is the G ... provide.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tip of M62096_PEA_1_P7, comprising at least 70%, optionally at least about 80%, preferably at least about 85%, of the sequence MTQNFRLMWNILLFPLNFS of M62096_PEA_1_P7 Provided is an isolated polypeptide encoding the tip of M62096_PEA_1_P7, preferably comprising a polypeptide that is at least about 90%, and most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding M62096_PEA_1_P8, corresponding to amino acids 1-736 of KF5C_HUMAN, corresponding to amino acids 1-736 of M62096_PEA_1_P8 MADPAECSIKVMCRFRPLNEAEILRGDKFIPKFKGDETVVIGQGKPYVFDRVLPPNTTQEQVYNACAKQIVKDVLEGYNGTIFAYGQTSSGKTHTMEGKLHDPQLMGIIPRIAHDIFDHIYSMDENLEFHIKVSYFEIYLDKIRDLLDVSKTNLAVHEDKNRVPYVKGCTERFVSSPEEVMDVIDEGKANRHVAVTNMNEHSSRSHSIFLINIKQENVETEKK SGKLYLVDLAGSEKVSKTGAEGAVLDEAKNINKSLSALGNVISALAEGTKTHVPYRDSKMTRILQDSLGGNCRTTIVICCSPSVFNEAETKSTLMFGQRAKTIKNTVSVNLELTAEEWKKKYEKEKEKNKTLKNVIQHLEMELNRWRNGEAVPEDEQISAKDQKNLEPCDNTPIIDNIAPVVAGISTEEKEKYDEEISSLYRQLDDKDDEINQQSQLAEKLKQQMLDQDELLASTRRDYEKIQEELTRLQIENEAAKDEVKEVLQALEELAVNYDQKSQEVEDKTRANEQLTDELAQKTTTLTTTQRELSQLQELSNHQKKRATEILNLLLK If the following elements are only required to be a part, but not limited to a member of a member of a member of a member, a member of a member of a member, a member of a member, a member of a member, only a member of a member of a s, b, ss, e, ss, e, ses, rela ,,,,,,,,,,,,,,,,,,,,,,,,,,,,, only sss. Preferably comprises a second amino acid sequence which is at least 90%, most preferably at least 95% homologous An isolated chimeric polypeptide encoding M62096_PEA_1_P8, wherein the first and second amino acid sequences are adjacent and in sequential order.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding M62096_PEA_1_P9, corresponding to amino acids 1-454 of KF5C_HUMAN, corresponding to amino acids 1-454 of M62096_PEA_1_P9 MADPAECSIKVMCRFRPLNEAEILRGDKFIPKFKGDETVVIGQGKPYVFDRVLPPNTTQEQVYNACAKQIVKDVLEGYNGTIFAYGQTSSGKTHTMEGKLHDPQLMGIIPRIAHDIFDHIYSMDENLEFHIKVSYFEIYLDKIRDLLDVSKTNLAVHEDKNRVPYVKGCTERFVSSPEEVMDVIDEGKANRHVAVTNMNEHSSRSHSIFLINIKQENVETEKK The first amino acid sequence at least 90% homologous to EsujikeieruwaierubuidierueijiesuikeibuiesukeitijieiijieibuierudiieikeienuaienukeiesueruesueierujienubuiaiesueierueiijitikeitieichibuiPiwaiarudiesukeiemutiaruaierukyudiesuerujijienushiarutitiaibuiaishishiesuPiesubuiefuenuieiitikeiesutieruemuefujikyuarueikeitiaikeienutibuiesubuienueruierutieiiidaburyukeikeikeiwaiikeiikeiikeienukeitierukeienubuiaikyueichieruiemuieruenuarudaburyuaruenujiieibuiPiidiikyuaiesueikeidikyukeienueruiPishidienutiPiaiaidienuaieiPibuibuieijiaiesutiiikeiikeiwaidiiiaiesuesueruwaiarukyuerudiDKDDEINQQSQLAEKLKQQMLDQDE, sequence VKNAIYFFFHKVLLLLFVVDVCSRNLIGIEAFHNYRIMWKFLGRC corresponding to amino acids 455-514 of M62096_PEA_1_P9 A polypeptide having FTASYKLIITE FRK and a second amino acid sequence which is at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous; Provided is an isolated chimeric polypeptide encoding M62096_PEA_1_P9, wherein the amino acid sequence of 1 and the second amino acid sequence are in contiguous and sequential order.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of M62096_PEA_1_P9, which is at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, preferably at least about 80% More preferably, provided is an isolated polypeptide encoding the tail of M62096_PEA_1_P9, comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding M62096_PEA_1_P10, comprising a polypeptide having the sequence MTQNFRLMWNILLFPLNFS corresponding to amino acids 1-19 of M62096_PEA_1_P10, at least 70%, optionally at least 80 %, Preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous to the first amino acid sequence and corresponds to amino acids 738 to 815 of KF5C_HUMAN and also to amino acids 20 to 97 of M62096_PEA_1_P10 LNQKLQLEQEKLSSDYNKLKIEDQ EREMKLEKLLLLNDKREQAREDLKGLEETVSRELQTLHNLRKLFVQDLT At least 70%, optionally at least 80%, preferably at least 85%, more preferably a second amino acid sequence at least 90% homologous to RVKK and a polypeptide having the sequence VSSLCLNGTEKKIKDGREESFSVEISLA corresponding to amino acids 98 to 125 of M62096_PEA_1_P10 Comprises a third amino acid sequence which is at least 90%, most preferably at least 95% homologous, the first amino acid sequence, the second amino acid sequence and the third amino acid sequence being adjacent and contiguous An isolated chimeric polypeptide encoding M62096_PEA_1_P10 is provided.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tip of M62096_PEA_1_P10, comprising at least 70%, optionally at least about 80%, preferably at least about 85%, of the sequence MTQNFRLMWNILLFPLNFS of M62096_PEA_1_P10 Provided is an isolated polypeptide encoding the tip of M62096_PEA_1_P10, preferably comprising a polypeptide that is at least about 90%, and most preferably at least about 95% homologous.

  According to a preferred embodiment of the invention, an isolated polypeptide encoding the tail of M62096_PEA_1_P10, comprising at least 70%, optionally at least about 80%, preferably at least about 85%, of the sequence VSSLCLNGTEKKIKDGREESFSVEISLA in M62096_PEA_1_P10 More preferably, provided is an isolated polypeptide encoding the tail of M62096_PEA_1_P10, comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding M62096_PEA_1_P11, corresponding to amino acids 1-372 of KF5C_HUMAN, corresponding to amino acids 1-372 of M62096_PEA_1_P11 MADPAECSIKVMCRFRPLNEAEILRGDKFIPKFKGDETVVIGQGKPYVFDRVLPPNTTQEQVYNACAKQIVKDVLEGYNGTIFAYGQTSSGKTHTMEGKLHDPQLMGIIPRIAHDIFDHIYSMDENLEFHIKVSYFEIYLDKIRDLLDVSKTNLAVHEDKNRVPYVKGCTERFVSSPEEVMDVIDEGKANRHVAVTNMNEHSSRSHSIFLINIKQENVETE KLSGKLYLVDLAGESEKVSKTGEGAGELDEAKNINKSLSALGNVISALAEGTKTHVPYRDSKMTRILQSLEGNCRTSIVICSPSVFNEAETKSTLMFGQRAKTIKNTVSVNLELTAE A clubhead that is at least 90% homologous to the HKK EK EK EK EK EK EK EMLE NLR JH, a 11, 620 620 620 620 620 Comprises a second amino acid sequence which is at least 90%, most preferably at least 95% homologous, said first amino acid sequence and 2 amino acid sequences, contiguous and in sequential order, provides an isolated chimeric polypeptide coding M62096_PEA_1_P11.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of M62096_PEA_1_P11, comprising at least 70%, optionally at least about 80%, preferably at least about 85%, of the sequence DFLAAHVFGKLLE in M62096_PEA_1_P11. More preferably, provided is an isolated polypeptide encoding the tail of M62096_PEA_1_P11, comprising a polypeptide that is at least about 90%, and most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding M62096_PEA_1_P12, corresponding to amino acids 1-323 of KF5C_HUMAN, corresponding to amino acids 1-323 of M62096_PEA_1_P12 MADPAECSIKVMCRFRPLNEAEILRGDKFIPKFKGDETVVIGQGKPYVFDRVLPPNTTQEQVYNACAKQIVKDVLEGYNGTIFAYGQTSSGKTHTMEGKLHDPQLMGIIPRIAHDIFDHIYSMDENLEFHIKVSYFEIYLDKIRDLLDVSKTNLAVHEDKNRVPYVKGCTERFVSSPEEVMDVIDEGKANRHVAVTNMNEHSSRSHSIFLINIKQENVETE KLSGKLYLVDLAGSEK VSKTGAEGAN LEXN INKSLSA LGN VISALA EGTK THVPYRDSKTMTRILQDSLGGNCRTTIVICCS VFNEATKSTLMFGQR The first amino acid sequence which is at least 90% homologous to the M62096_PEA_1_P12 and the polypeptide having the sequence V corresponding to amino acids 324 to 324 at least 70% Comprises M62096_PEA_1_P12, which comprises a second amino acid sequence which is at least 90%, most preferably at least 95% homologous, said first amino acid sequence and the second amino acid sequence being adjacent and in sequential order Isolated chimeric polypeptide Subjected to.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding T99080_PEA_4_P5, comprising at least 70%, optionally at least 80% of a polypeptide having the sequence MPASARAGAGGLLLAFLRALGCAGRAPGLS corresponding to amino acids 1 to 30 of T99080_PEA_4_P5 Preferably corresponds to a first amino acid sequence of at least 85%, more preferably at least 90%, most preferably at least 95% and corresponds to amino acids 1 to 99 of ACYO_HUMAN_V1 and also to amino acids 31 to 129 of T99080_PEA_4_P5 An isolated chimeric polypeptide encoding T99080_PEA_4_P5, comprising a second amino acid sequence at least 90% homologous to ETRGSPKSHIDKANFNNEK VILKLDYSDFQIVK, wherein said first and second amino acid sequences are adjacent and in sequential order provide.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tip of T99080_PEA_4_P5, comprising at least 70%, optionally at least about 80%, preferably at least about 85%, of the sequence MPASARAGAGAGLLLAFLRALGCAGRAPGLS of T99080_PEA_4_P5 Provided is an isolated polypeptide encoding the tip of T99080_PEA_4_P5, preferably comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding T99080_PEA_4_P8, wherein the polypeptide has a sequence M corresponding to amino acids 1 to 1 of T99080_PEA_4_P8 and at least 70%, optionally at least 80% Preferably, at least 85%, more preferably at least 90%, most preferably at least 95% of the first amino acid sequence homologous and corresponding to amino acids 28 to 99 of ACYO_HUMAN_V1 and also to amino acids 2 to 73 of T99080_PEA_4_P8 And a second amino acid sequence that is at least 90% homologous The first amino acid sequence and a second amino acid sequence, contiguous and in sequential order, provides an isolated chimeric polypeptide coding T99080_PEA_4_P8.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding T08446_PEA_1_P18, corresponding to amino acids 1-185 of SNXQ_HUMAN, at least 90% homologous with the corresponding MLSLSLCSHLWGPLILSALQARSTDSLDGPGEGSVQPLPTAGGPSVKGKPGKRLSAPRGPFPRLADCAHFHYENVDFGHIQLLLSPDREGPSLSGENELVFGVQVTCQGRSWPVLRSYDDFRSLDAHLHRCIFDRRFSCLPELPPPPEGARAAQMLVPLLLQYLETLSGLVDSNLNCGPVLTWME to amino acids 1-185 of T08446_PEA_1_P18 First amino acid sequence, T08446_PEA_1_ 18 sequence corresponding to amino acids 186 to 1305 of LDNHGRRLLLSEEASLNIPAVAAAHVIKRYTAQAPDELSFEVGDIVSVIDMPPTEDRSWWRGKRGFQVGFFPSECVELFTERPGPGLKADADGPPCGIPAPQGISSLTSAVPRPRGKLAGLLRTFMRSRPSRQRLRQRGILRQRVFGCDLGEHLSNSGQDVPQVLRCCSEFIEAHGVVDGIYRLSGVSSNIQRLRHEFDSERIPELSGPAFLQDIHSVSSLCKLYFRELPNPLLTYQLYGKFSEAMSVPGEEERLVRVHDVIQQLPPPHYRTLEYLLRHLARMARHSANTSMHARNLAIVWAPNLLRSME ESVGMGGAAAFREVRVQSVVVEFLLTHVDVLFSDTFTSAGLDPAGRCLLPRPKSLAGSCPSTRLLTLEEAQARTQGRLGTPTEPTTPKAPASPAERRKGERGEKQRKPGGSSWKTFFALGRGPSVPRKKPLPWLGGTRAPPQPSGSRPDTVTLRSAKSEESLSSQASGAGLQRLHRLRRPHSSSDAFPVGPAPAGSCESLSSSSSSESSSSESSSSSSESSAAGLGALSGSPSHRTSAWLDDGDELDFSPPRCLEGLRGLDFDPLTFRCSSPTPGDPAPPASPAPPAPASAFPPRVTPQAISPRGPTSPASPAALDISEPLAVSVPPAVLELL GAGGAPASATPTPALSPGRSLRPHLIPLLLRGAEAPLTDACQQEMCSKLRGAQGPLGPDMESPLPPPPLSLLRPGGAPPPPPKNPARLMALALAERAQQVAEQQSQQECGGTPPASQSPFHRSLSLEVGGEPLGTSGSGPPPNSLAHPGAWVPGPPPYLPRQQSDGSLLRSQRPMGTSRRGLRGPAQVSAQLRAGGGGRDAPEAAAQSPCSVPSQVPTPGFFSPAPRECLPPFLGVPKPGLYPLGPPSFQPSSPAPVWRSSLGPPAPLDRGENLYYEIGASEGSPYSGPTRSWSPFRSMPPDRLNASYGMLGQSPPLHRSPDFLLSYPPAPSC PPDHLGYSAPQHPARRPTPPESPLYSSLPSPAPRSRSDPGPP VPRLPQ KQRAP WGPRTPHRVPGPWGPPPEPLLLYRAAPPAYGRGGELHRGSLYRNGGQRGEGAGPPPPYPTPSWSLEGEGQTRSYC and at least 70%, optionally at least 80%, and at least 90% Provided is an isolated chimeric polypeptide encoding T08446_PEA_1_P18, wherein the amino acid sequence of 1 and the second amino acid sequence are adjacent and in sequential order.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoded by the tail T08446_PEA_1_P18, sequences in T08446_PEA_1_P18 LDNHGRRLLLSEEASLNIPAVAAAHVIKRYTAQAPDELSFEVGDIVSVIDMPPTEDRSWWRGKRGFQVGFFPSECVELFTERPGPGLKADADGPPCGIPAPQGISSLTSAVPRPRGKLAGLLRTFMRSRPSRQRLRQRGILRQRVFGCDLGEHLSNSGQDVPQVLRCCSEFIEAHGVVDGIYRLSGVSSNIQRLRHEFDSERIPELSGPAFLQDIHSVSSLCKLYFRELPNPLLTYQLYGKFSEAMSVPGEEERLVR HDVIQQLPPPHYRTLEYLLRHLARMARHSANTSMHARNLAIVWAPNLLRSMELESVGMGGAAAFREVRVQSVVVEFLLTHVDVLFSDTFTSAGLDPAGRCLLPRPKSLAGSCPSTRLLTLEEAQARTQGRLGTPTEPTTPKAPASPAERRKGERGEKQRKPGGSSWKTFFALGRGPSVPRKKPLPWLGGTRAPPQPSGSRPDTVTLRSAKSEESLSSQASGAGLQRLHRLRRPHSSSDAFPVGPAPAGSCESLSSSSSSESSSSESSSSSSESSAAGLGALSGSPSHRTSAWLDDGDELDFSPPRCLEGLRGLDFDPLTFRCSSPTPGDPAP ASPAPPAPASAFPPRVTPQAISPRGPTSPASPAALDISEPLAVSVPPAVLELLGAGGAPASATPTPALSPGRSLRPHLIPLLLRGAEAPLTDACQQEMCSKLRGAQGPLGPDMESPLPPPPLSLLRPGGAPPPPPKNPARLMALALAERAQQVAEQQSQQECGGTPPASQSPFHRSLSLEVGGEPLGTSGSGPPPNSLAHPGAWVPGPPPYLPRQQSDGSLLRSQRPMGTSRRGLRGPAQVSAQLRAGGGGRDAPEAAAQSPCSVPSQVPTPGFFSPAPRECLPPFLGVPKPGLYPLGPPSFQPSSPAPVWRSSLGPPAPLDRGENLYYEIGA SEGSPYSGPTRSWSPFRSMPPDRLNASYGMLGQSPPLHRSPDFLLSYPPAPSCFPPDHLGYSAPQHPARRPTPPEPLYVNLALGPRGPSPASSSSSSPPAHPRSRSDPGPPVPRLPQKQRAPWGPRTPHRVPGPWGPPEPLLLYRAAPPAYGRGGELHRGSLYRNGGQRGEGAGPPPPYPTPSWSLHSEGQTRSYC at least 70%, optionally at least about 80%, single preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the polypeptide encoding T08446_PEA_1_P18 An isolated polypeptide is provided.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding T08446_PEA_1_P18, corresponding to amino acids 1-443 of T08446_PEA_1_P18 sequence MLSLSLCSHLWGPLILSALQARSTDSLDGPGEGSVQPLPTAGGPSVKGKPGKRLSAPRGPFPRLADCAHFHYENVDFGHIQLLLSPDREGPSLSGENELVFGVQVTCQGRSWPVLRSYDDFRSLDAHLHRCIFDRRFSCLPELPPPPEGARAAQMLVPLLLQYLETLSGLVDSNLNCGPVLTWMELDNHGRRLLLSEEASLNIPAVAAAHVIKRYTAQAPDELSFEVGDIVSVIDMPPTEDRSWW A part of the ssssss 14DeI 14D, D, D, G, S, GSM only, only, not limited to the above, not limited to the above, not limited to the above, not limited to us. The amino acids of T08446_PEA_1_P18 corresponding to 1 to 674 Also it corresponds to the 444~1117 HDVIQQLPPPHYRTLEYLLRHLARMARHSANTSMHARNLAIVWAPNLLRSMELESVGMGGAAAFREVRVQSVVVEFLLTHVDVLFSDTFTSAGLDPAGRCLLPRPKSLAGSCPSTRLLTLEEAQARTQGRLGTPTEPTTPKAPASPAERRKGERGEKQRKPGGSSWKTFFALGRGPSVPRKKPLPWLGGTRAPPQPSGSRPDTVTLRSAKSEESLSSQASGAGLQRLHRLRRPHSSSDAFPVGPAPAGSCESLSSSSSSESSSSESSSSSSESSAAGLGALSGSPSHRTSAWLDDGDELDFSPPRCLEGLRGLDFDPLT FRCSSPTPGDPAPPASPAPPAPASAFPPRVTPQAISPRGPTSPASPAALDISEPLAVSVPPAVLELLGAGGAPASATPTPALSPGRSLRPHLIPLLLRGAEAPLTDACQQEMCSKLRGAQGPLGPDMESPLPPPPLSLLRPGGAPPPPPKNPARLMALALAERAQQVAEQQSQQECGGTPPASQSPFHRSLSLEVGGEPLGTSGSGPPPNSLAHPGAWVPGPPPYLPRQQSDGSLLRSQRPMGTSRRGLRGPAQVSAQLRAGGGGRDAPEAAAQSPCSVPSQVPTPGFFSPAPRECLPPFLGVPKPGLYPLGPPSFQPSSPAPVWRSSLGPPA And at least 90% homologous second amino acid sequence LDRGENLYYEIGASEGSPYSG, a crosslinking amino acid P corresponding to amino acid 1118 of T08446_PEA_1_P18, corresponding to amino acids 676-862 of Q9NT23, small and TRSWSPFRSMPPDRLNASYGMLGQSPPLHRSPDFLLSYPPAPSCFPPDHLGYSAPQHPARRPTPPEPLYVNLALGPRGPSPASSSSSSPPAHPRSRSDPGPPVPRLPQKQRAPWGPRTPHRVPGPWGPPEPLLLYRAAPPAYGRGGELHRGSLYRNGGQRGEGAGPPPPYPTPSWSLHSEGQTRSYC corresponding to amino acids 1119-1305 of T08446_PEA_1_P18 T08446_PEA_1_P18, which comprises a third amino acid sequence that is both 90% homologous, the first amino acid sequence, the second amino acid sequence, the bridging amino acid, and the third amino acid sequence being adjacent and in sequential order Provided is an isolated chimeric polypeptide that encodes.

According to a preferred embodiment of the present invention, an isolated polypeptide encoded by the tip of T08446_PEA_1_P18, sequences T08446_PEA_1_P18 MLSLSLCSHLWGPLILSALQARSTDSLDGPGEGSVQPLPTAGGPSVKGKPGKRLSAPRGPFPRLADCAHFHYENVDFGHIQLLLSPDREGPSLSGENELVFGVQVTCQGRSWPVLRSYDDFRSLDAHLHRCIFDRRFSCLPELPPPPEGARAAQMLVPLLLQYLETLSGLVDSNLNCGPVLTWMELDNHGRRLLLSEEASLNIPAVAAAHVIKRYTAQAPDELSFEVGDIVSVIDMPPTEDRSWWRGKRGFQVGFFPSE A part of a group of a member of a group of a member of a group is only a part of a group of a member of a member, only a part of a member of a group, only a member of a member. Provide an isolated polypeptide.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding T08446_PEA_1_P18, corresponding to amino acids 1 to 1010 of T08446_PEA_1_P18 sequence MLSLSLCSHLWGPLILSALQARSTDSLDGPGEGSVQPLPTAGGPSVKGKPGKRLSAPRGPFPRLADCAHFHYENVDFGHIQLLLSPDREGPSLSGENELVFGVQVTCQGRSWPVLRSYDDFRSLDAHLHRCIFDRRFSCLPELPPPPEGARAAQMLVPLLLQYLETLSGLVDSNLNCGPVLTWMELDNHGRRLLLSEEASLNIPAVAAAHVIKRYTAQAPDELSFEVGDIVSVIDMPPTEDRSW RGKRGFQVGFFPSECVELFTERPGPGLKADADGPPCGIPAPQGISSLTSAVPRPRGKLAGLLRTFMRSRPSRQRLRQRGILRQRVFGCDLGEHLSNSGQDVPQVLRCCSEFIEAHGVVDGIYRLSGVSSNIQRLRHEFDSERIPELSGPAFLQDIHSVSSLCKLYFRELPNPLLTYQLYGKFSEAMSVPGEEERLVRVHDVIQQLPPPHYRTLEYLLRHLARMARHSANTSMHARNLAIVWAPNLLRSMELESVGMGGAAAFREVRVQSVVVEFLLTHVDVLFSDTFTSAGLDPAGRCLLPRPKSLAGSCPSTRLLTLEEAQARTQGRLGTP EPTTPKAPASPAERRKGERGEKQRKPGGSSWKTFFALGRGPSVPRKKPLPWLGGTRAPPQPSGSRPDTVTLRSAKSEESLSSQASGAGLQRLHRLRRPHSSSDAFPVGPAPAGSCESLSSSSSSESSSSESSSSSSESSAAGLGALSGSPSHRTSAWLDDGDELDFSPPRCLEGLRGLDFDPLTFRCSSPTPGDPAPPASPAPPAPASAFPPRVTPQAISPRGPTSPASPAALDISEPLAVSVPPAVLELLGAGGAPASATPTPALSPGRSLRPHLIPLLLRGAEAPLTDACQQEMCSKLRGAQGPLGPDMESPLPPPPLSLLRPGGAPPPPP A polypeptide having at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous amino acid sequence of the amino acid sequence of LRGPAQVSAGLAGGGGRDAPEAAAQSPCSVP SQVPTPGFSPAPLPLPGVP KPGLYPLGPPSFQPSSPAVWRSSLGP corresponding to .about.295 and corresponding to amino acids 1011 to 1305 of T08446_PEA_1_P18 APLDRGENLYYEIGASEGSPYSGPTRSWSPFRSMPPDRLNASYGMLGQSPPLHRSPDFLLSYPPAPSCFPPDHLGYSAPQHPARRPTPPEPLYVNLALGPRGPSPASSSSSSPPAHPRSRSDPGPPVPRLPQKQRAPWGPRTPHRVPGPWGPPEPLLLYRAAPPAYGRGGELHRGSLYRNGGQRGEGAGPPPPYPTPSWSLHSEGQTRSYC and and at least 90% homologous to a second amino acid sequence, the first amino acid sequence and a second amino acid sequence, contiguous and in sequential order, the isolated chimeric polypeptide encoding T08446_PEA_1_P18 I will provide a.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoded by the tip of T08446_PEA_1_P18, sequences T08446_PEA_1_P18 MLSLSLCSHLWGPLILSALQARSTDSLDGPGEGSVQPLPTAGGPSVKGKPGKRLSAPRGPFPRLADCAHFHYENVDFGHIQLLLSPDREGPSLSGENELVFGVQVTCQGRSWPVLRSYDDFRSLDAHLHRCIFDRRFSCLPELPPPPEGARAAQMLVPLLLQYLETLSGLVDSNLNCGPVLTWMELDNHGRRLLLSEEASLNIPAVAAAHVIKRYTAQAPDELSFEVGDIVSVIDMPPTEDRSWWRGKRGFQVGFFPSE VELFTERPGPGLKADADGPPCGIPAPQGISSLTSAVPRPRGKLAGLLRTFMRSRPSRQRLRQRGILRQRVFGCDLGEHLSNSGQDVPQVLRCCSEFIEAHGVVDGIYRLSGVSSNIQRLRHEFDSERIPELSGPAFLQDIHSVSSLCKLYFRELPNPLLTYQLYGKFSEAMSVPGEEERLVRVHDVIQQLPPPHYRTLEYLLRHLARMARHSANTSMHARNLAIVWAPNLLRSMELESVGMGGAAAFREVRVQSVVVEFLLTHVDVLFSDTFTSAGLDPAGRCLLPRPKSLAGSCPSTRLLTLEEAQARTQGRLGTPTEPTTPKAPASPAER KGERGEKQRKPGGSSWKTFFALGRGPSVPRKKPLPWLGGTRAPPQPSGSRPDTVTLRSAKSEESLSSQASGAGLQRLHRLRRPHSSSDAFPVGPAPAGSCESLSSSSSSESSSSESSSSSSESSAAGLGALSGSPSHRTSAWLDDGDELDFSPPRCLEGLRGLDFDPLTFRCSSPTPGDPAPPASPAPPAPASAFPPRVTPQAISPRGPTSPASPAALDISEPLAVSVPPAVLELLGAGGAPASATPTPALSPGRSLRPHLIPLLLRGAEAPLTDACQQEMCSKLRGAQGPLGPDMESPLPPPPLSLLRPGGAPPPPPKNPARLMALALAERA QQVAEQQSQQEGGTPTPASQSPHRSLSLSLEVGGEPLGTSGSGPRPSNLAHPGAWVPGPPPYLPRQQQSDGLLRSPRPMTSRRG and at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous polypeptide, including T80446_PEA_18P Provided is an isolated polypeptide.

  According to a preferred embodiment of the present invention, it is an isolated chimeric polypeptide coding for T08446_PEA_1_P18 and corresponding to amino acids 1-154 of T08446_PEA. , Preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous to the first amino acid sequence. And, corresponding to amino acids 1 to 861 of BAC86902, corresponding to amino acids 155 to 1015 of T08446_PEA_1_P18 MLVPLLLQYLETLSGLVDSNLNCGPVLTWMELDNHGRRLLLSEEASLNIPAVAAAHVIKRYTAQAPDELSFEVGDIVSVIDMPPTEDRSWWRGKRGFQVGFFPSECVELFTERPGPGLKADADGPPCGIPAPQGISSLTSAVPRPRGKLAGLLRTFMRSRPSRQRLRQRGILRQRVFGCDLGEHLSNSGQDVPQVLRCCSEFIEAHGVVDGIYRLSGVSSNIQRLRHEFDSERIPELSGPAFLQDIHSVSSLCKLYFRELPNPLLTYQLYGK SEAMSVPGEEERLVRVHDVIQQLPPPHYRTLEYLLRHLARMARHSANTSMHARNLAIVWAPNLLRSMELESVGMGGAAAFREVRVQSVVVEFLLTHVDVLFSDTFTSAGLDPAGRCLLPRPKSLAGSCPSTRLLTLEEAQARTQGRLGTPTEPTTPKAPASPAERRKGERGEKQRKPGGSSWKTFFALGRGPSVPRKKPLPWLGGTRAPPQPSGSRPDTVTLRSAKSEESLSSQASGAGLQRLHRLRRPHSSSDAFPVGPAPAGSCESLSSSSSSESSSSESSSSSSESSAAGLGALSGSPSHRTSAWLDDGDELDFSPPRCLEGLRGLDFDP And at least 90% homologous second amino acid sequence ErutiefuarushiesuesuPitipijidipiEipiPiEiesupiEipipieipasuEiefupiPiarubuitiPikyueiaiesuPiaruJipitiesuPiEiesupieieierudiaiesuiPierueibuiesubuiPiPieibuieruieruerujieijijieiPieiesueitiPitiPieieruesuPijiaruesueruaruPieichieruaiPieruerueruarujieiieiPierutidieishikyukyuiemushiesukeieruarujieikyuJipieruJipidiemuiesupierupipipipieruesuerueruaruPijijieiPipipipipikeienuPieiarueruemueierueierueiiarueikyukyubuieiikyukyuesukyukyuishijijitiPiPieiesukyuesuPiefueichiaruesueruesueruibuijijiiPierujitiesujiesuJipipipienuesuerueieichiPijieidaburyubuiPiJipipipiwaieruPiaruQQSDGSLLRSQRPMGTSRRGLRGPA, sequence QVSAQLRAGGGGRDAPEA corresponding to amino acids 1016 to 1,043 in T08446_PEA_1_P18 A third amino acid sequence which is at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous to a polypeptide having AQSPCSVPS and amino acid 862 of BAC 86902 A sequence of at least 90% A peptide having the sequence APQHPARRPTPPEPLYVNLAGPGPSPASSSSSPPAHPRSSQPQQQRAP WGPRTPHRVPGPWGPPE PLLLYRAAPPAYGRGGELHRGSLYRNGGQRGEGAPPPP YPTGSTHSQSQRSQ SQHQSIG SQH corresponding to the amino acids 1172 to 1305 and at least 80% as appropriate And the first amino acid sequence, the second amino acid sequence, the third amino acid sequence, the fourth amino acid sequence, and the fifth amino acid sequence are adjacent and in a consecutive order, T08446_PEA_ Provided is an isolated chimeric polypeptide encoding 1_P18.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tip of T08446_PEA_1_P18, which is the sequence of T08446_PEA_1_P18, MLSLSLCSHLWGPLILSALQARSTDSLDGPGEGSVQPGPGPGPGOKRFPHHPHILPLPDEGGLITQIV GELQ I The end of T08446_PEA_1_P18, preferably comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous. It provides an isolated polypeptide encoding.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the edge portion of T08446_PEA_1_P18, which is at least 70%, optionally at least about 80%, preferably at least 70% of the sequence encoding QVSAQLRAGGGGRDAPEAAAQSPCSVPPS corresponding to T08446_PEA_1_P18 Provided is an isolated polypeptide encoding an edge portion of T08446_PEA_1_P18 that comprises an amino acid sequence that is at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of T08446_PEA_1_P18, which is in the sequence of T08446_PEA_1_P18: More preferably, provided is an isolated polypeptide encoding the tail of T08446_PEA_1_P18, comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous. To.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding T11628_PEA_1_P2 comprising a polypeptide having the sequence MGLSDGEWQLVLNVWGKVEADIPGHGQEVLIRLFKGHPETLEKDFDKFKHLKSEDE corresponding to amino acids 1 to 55 of T11628_PEA_1_P2 and at least 70%, optionally at least 80% , Preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous to the first amino acid sequence and corresponding to amino acids 1 to 99 of Q8WVH6 and also to amino acids 56 to 154 of T11628_PEA_1_P2 An isolated chimeric polypeptide encoding T11628_PEA_1_P2 comprising a second amino acid sequence that is at least 90% homologous to YLEFISECII QVLQSKHPGDFGADAQGAMNKALELFRKDMASNYKELGFQG, wherein said first and second amino acid sequences are adjacent and in a sequential order provide.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tip of T11628_PEA_1_P2, which is at least 70%, optionally at least about 80%, preferably at least about 85%, of the sequence Provided is an isolated polypeptide encoding the tip of T11628_PEA_1_P2 that comprises a polypeptide that is preferably at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding T11628_PEA_1_P5, comprising: Provided is an isolated chimeric polypeptide encoding T11628_PEA_1_P5, comprising a first amino acid sequence.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding T11628_PEA_1_P7, corresponding to amino acids 1 to 134 of MYG_HUMAN_V1 and corresponding to amino acids 1 to 134 of T11628_PEA_1_P7, also corresponding to amino acids 1 to 134. At least 70%, optionally less, with a polypeptide having the first amino acid sequence and a sequence G corresponding to amino acids 135-135 of T11628_PEA_1_P7 And a second amino acid sequence that is 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous, said first and second amino acid sequences being adjacent Provided is an isolated chimeric polypeptide encoding T11628_PEA_1_P7, and in sequential order.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding T11628_PEA_1_P10, comprising at least 70%, optionally at least 80%, of a polypeptide having the sequence MGLSDGEWQLVLNVWGKVEADIPGHGQEVLIRLFKGHPETLEKDFDKFKHLKDEDE corresponding to amino acids 1 to 55 of T11628_PEA_1_P10 , Preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous to the first amino acid sequence, and corresponding to amino acids 1 to 99 of Q8WVH6 and also to amino acids 56 to 154 of T11628_PEA_1_P10 An isolated chimeric polypeptide encoding T11628_PEA_1_P10, comprising a second amino acid sequence which is at least 90% homologous to PVKYLEFISECII QVLQSKHPGDFGADAQGAMNKALELFRKDMASNYKELGFQG, wherein said first and second amino acid sequences are adjacent and in sequential order provide.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tip of T11628_PEA_1_P10, which is at least 70%, optionally at least about 80%, preferably at least about 85%, of the sequence Provided is an isolated polypeptide encoding the tip of T11628_PEA_1_P10, which comprises a polypeptide that is preferably at least about 90%, and most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding R35137_PEA_1_PEA_1_PEA_1_P9, corresponding to amino acids 1-274 of ALAT_HUMAN_V1, corresponding to amino acids 1-274 of R35137_PEA_1_PEA_1_PEA_1_P9 MASSTGDRSQAVRHGLRAKVLTLDGMNPRVRRVEYAVRGPIVQRALELEQELRQGVKKPFTEVIRANIGDAQAMGQRPITFLRQVLALCVNPDLLSSPNFPDDAKKRAERILQACGGHSLGAYSVSSGIQLIREDVARYIERRDGGIPADPNNVFLSTGASDAIVTVLKLLVAGEGHTRTGVLIPIPQYPLYSATL A first amino acid sequence at least 90% homologous to IerujieibuikyubuidiwaiwaierudiiiarueidaburyueierudibuieiierueichiarueierujikyueiarudieichishiaruPiarueierushibuiaienuPijienupitijikyubuiQTRECIEAVIRFAFEERLFLLADEV, polypeptide at least 70% with a sequence corresponding to RGAGEREAGQQSAPVTPCALPGVPGQRVRRGFAVPLIQEGAHGDGAALRRAAGACLLPLHLQGLHGRVRAYEAGGGSRAMARPSSPDGPPPPPHLTWPCAGAGSAAAMWRW to amino acid 275-385 of R35137_PEA_1_PEA_1_PEA_1_P9, optionally at least 80%, preferably at least 85%, more preferably Is at least 90%, most preferably less Also provided is an isolated chimeric polypeptide encoding R35137_PEA_1_PEA_1_PEA_1_P9, comprising a second amino acid sequence that is also 95% homologous, said first amino acid sequence and said second amino acid sequence being adjacent and in sequential order .

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of R35137_PEA_1_PEA_1_PEA_1_P9, comprising: More preferably, it encodes the tail of R35137_PEA_1_PEA_1_PEA_1_P9, which comprises a polypeptide that is at least about 90%, most preferably at least about 95% homologous. To provide a releasing polypeptide.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding R35137_PEA_1_PEA_1_PEA_1_P8, it corresponds to amino acids 1 to 320 of ALAT_HUMAN_V1, corresponding to amino acids 1 to 320 of R35137_PEA_1_PEA_1_PEA_1_P8 MASSTGDRSQAVRHGLRAKVLTLDGMNPRVRRVEYAVRGPIVQRALELEQELRQGVKKPFTEVIRANIGDAQAMGQRPITFLRQVLALCVNPDLLSSPNFPDDAKKRAERILQACGGHSLGAYSVSSGIQLIREDVARYIERRDGGIPADPNNVFLSTGASDAIVTVLKLLVAGEGHTRTGVLIPIPQYPLYSATL A first amino acid sequence at least 90% homologous to IerujieibuikyubuidiwaiwaierudiiiarueidaburyueierudibuieiierueichiarueierujikyueiarudieichishiaruPiarueierushibuiaienuPijienupitijikyubuikyutiaruishiaiieibuiaiaruefueiefuiiarueruefueruerueidiibuiwaikyudienubuiwaieieijiesukyuefueichiesuefukeikeibuieruemuiMGPPYAGQQELASFHSTSKGYMGEC, polypeptide at least 70% with a sequence corresponding to VRTRRVGARGPWPGPPRPMGHPLLRT to amino acid 321-346 of R35137_PEA_1_PEA_1_PEA_1_P8, optionally at least 80%, preferably at least 85%, more preferably Comprises a second amino acid sequence which is at least 90%, most preferably at least 95% homologous, said first amino acid sequence and the second amino acid sequence Amino acid sequences, contiguous and in sequential order, provides an isolated chimeric polypeptide coding R35137_PEA_1_PEA_1_PEA_1_P8.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of R35137_PEA_1_PEA_1_PEA_1_P8, which is at least 70%, optionally at least about 80%, preferably at least about 85%, with the VTRTRVGARGPWPGPPRPMGH PLLRT in the sequence R35137_PEA_1_PEA_1_PEA_1_P8 More preferably, provided is an isolated polypeptide encoding the tail of R35137_PEA_1_PEA_1_PEA_1_P8, comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding R35137_PEA_1_PEA_1_PEA_1_P11, corresponding to amino acids 1-229 of ALAT_HUMAN_V1, corresponding to amino acids 1-229 of R35137_PEA_1_PEA_1_PEA_1_P11 MASSTGDRSQAVRHGLRAKVLTLDGMNPRVRRVEYAVRGPIVQRALELEQELRQGVKKPFTEVIRANIGDAQAMGQRPITFLRQVLALCVNPDLLSSPNFPDDAKKRAERILQACGGHSLGAYSVSSGIQLIREDVARYIERRDGGIPADPNNVFLSTGASDAIVTVLKLLVAGEGHTRTGVLIPIPQYPLYSA The first amino acid sequence which is at least 90% homologous to LAELGAVQVDYYLDEERAWALDVAELHRALQAR and corresponding to amino acids 455 to 496 of ALAT_HUMAN_V1 and also corresponding to amino acids 230 to 271 of R35137_PEA_1_PEA_1_PEA_1_P11 The present invention provides an isolated chimeric polypeptide encoding R35137_PEA_1_PEA_1_PEA_1_P11, wherein the first and second amino acid sequences are adjacent and in sequential order.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding the rim portion of R35137_PEA_1_PEA_1_PEA_1_P11, having a length “n”, where n is at least about 10 amino acids in length, optionally at least about at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length, most preferably at least about 50 amino acids in length), wherein at least two amino acids comprise RS; A polypeptide having a sequence beginning with any of the numbers 229-x to 229 and ending at the amino acid number 230 + ((n-2) -x), wherein x varies from 0 to n-2. Code the edge part of R35137_PEA_1_PEA_1_PEA_1_P11, including That provides isolated chimeric polypeptides.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding R35137_PEA_1_PEA_1_PEA_1_P2, corresponding to amino acids 1-274 of ALAT_HUMAN_V1, corresponding to amino acids 1-274 of R35137_PEA_1_PEA_1_PEA_1_P2 MASSTGDRSQAVRHGLRAKVLTLDGMNPRVRRVEYAVRGPIVQRALELEQELRQGVKKPFTEVIRANIGDAQAMGQRPITFLRQVLALCVNPDLLSSPNFPDDAKKRAERILQACGGHSLGAYSVSSGIQLIREDVARYIERRDGGIPADPNNVFLSTGASDAIVTVLKLLVAGEGHTRTGVLIPIPQYPLYSATL A first amino acid sequence at least 90% homologous to IerujieibuikyubuidiwaiwaierudiiiarueidaburyueierudibuieiierueichiarueierujikyueiarudieichishiaruPiarueierushibuiaienuPijienupitijikyubuiQTRECIEAVIRFAFEERLFLLADEV, polypeptide at least 70% with a sequence corresponding to RGAGEREAGQQSAPVTPCALPGVPGQRVRRGFAVPLIQEGAHGDGAALRRAAGACLLPLHLQGLHGRVRVPRRLCGGGEHGRCSAAADAEADECAAVPAGARTGPAGPGGQPARAHRPLLCAVPG to amino acid 275-399 of R35137_PEA_1_PEA_1_PEA_1_P2, optionally at least 80%, preferably at least 85%, more preferably At least An isolation encoding R35137_PEA_1_PEA_1_PEA_1_P2, which comprises a second amino acid sequence of 0%, most preferably at least 95% homology, said first amino acid sequence and said second amino acid sequence being adjacent and in sequential order Provided is a chimeric polypeptide.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of R35137_PEA_1_PEA_1_PEA_1_P2, which is a tag that is used in the sequence of R35137_PEA_1_PEA_1_PEA_1_P2 and which is RGIGETAGQQQRPVQQQRVHQGLEGALGLIGITHI, which is an isolated polypeptide encoding the tail of G35. More preferably, R35137_PEA_1_PEA_1_PEA_ comprising a polypeptide that is at least about 90%, and most preferably at least about 95% homologous. It provides an isolated polypeptide encoding a tail _p2.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding R35137_PEA_1_PEA_1_PEA_1_P4, corresponding to amino acids 1-494 of ALAT_HUMAN_V1, corresponding to amino acids 1-494 of R35137_PEA_1_PEA_1_PEA_1_P4 MASSTGDRSQAVRHGLRAKVLTLDGMNPRVRRVEYAVRGPIVQRALELEQELRQGVKKPFTEVIRANIGDAQAMGQRPITFLRQVLALCVNPDLLSSPNFPDDAKKRAERILQACGGHSLGAYSVSSGIQLIREDVARYIERRDGGIPADPNNVFLSTGASDAIVTVLKLLVAGEGHTRTGVLIPIPQYPLYSATL The first amino acid sequence at least 90% homologous to ELGAVQVDYYLDEERAWALDVAELHRALGQARDHCRPRALCVINPGNPTGQVQTRECIEAVIRFAFEERLFLLADEVYQDNVYAAGSQFHSFKKVLMEMGPPYAGQQELASFHSTSKGYMGECGFRGGYVEVVNMDAAVQQQMLKLMSVRLCPPVPGQALLDLVVSPPAPTDPSFAQFQAEKQAVLAELAAKAKLTEQVFNEAPGISCNPVQGAMYSFPRVQLPPRAVERAQELGLAPDMFFCLRLLEETGICVVPGSGFGQREGTYHFRMTILPPLEKLRLLLEKLSRFHAKFTLE, R35137_PEA_1 PEA_1_PEA_1_P4 amino acid sequence corresponding to amino acids 495 to 555 of SPGRLWSPLYLLLMPGGVGWGCWAPASLQVPNKAVWQSDSKKEALAAAWPAPTCPLQA at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous An isolated chimeric polypeptide encoding R35137_PEA_1_PEA_1_PEA_1_P4, comprising two amino acid sequences, wherein the first amino acid sequence and the second amino acid sequence are adjacent and in sequential order.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of R35137_PEA_1_PEA_1_P4, at least 70, at least 70, at least 70. More preferably, provided is an isolated polypeptide encoding the tail of R35137_PEA_1_PEA_1_PEA_1_P4, comprising a polypeptide that is at least about 90%, and most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding R11723_PEA_1_P6, which corresponds to amino acids 1 to 110 of R11723_PEA_1_P6. , Preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous to the first amino acid sequence, corresponding to amino acids 1-112 of Q8IXM0, amino acid 11 of R11723_PEA_1_P6 ... A corresponding amino acid sequence includes a second amino acid sequence at least 90% homologous to the second amino acid sequence, and the corresponding ones Provided is a polypeptide.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tip of R11723_PEA_1_P6, comprising: R11723_PEA_1_P6, which is a sequence of MWVLGIAATFCCFLFLLPALQQQCYQCEEFQLNNDCSSPEFIVNCNCTVNVQQEMMECSASLACIAGSAG GGLAPG E LEG I Provided is an isolated polypeptide encoding the tip of R11723_PEA_1_P6, preferably comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding R11723_PEA_1_P6, which corresponds to amino acids 1 to 83 of Q96AC2 and also to amino acids 1 to 83 of R11723_PEA_1_P6. The first amino acid sequence and the sequence corresponding to amino acids 84 to 222 of R11723_PEA_1_P6 SPCRGLAPGREEQRALHKAGAVGGGVRMYAQALLVVGVLQRQAAAQHLHEHPPKLLRGHRVQERVDDRAEVEKRLREGEEDHVRPEVGPR A polypeptide having at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95%, of a second amino acid sequence homologous to the polypeptide having VVLGFGRSHDPPPNLVGHPAYGQCHNNQPWADTSRRERQRKHSMRTQ; Provided is an isolated chimeric polypeptide encoding R11723_PEA_1_P6 in which the first and second amino acid sequences are in contiguous and sequential order.

  According to a preferred embodiment of the present invention, according to a preferred embodiment of the invention, according to a preferred embodiment of the invention An isolated polypeptide encoding the tail of R11723_PEA_1_P6, more preferably comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous To provide.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding R11723_PEA_1_P6, which corresponds to amino acids 1 to 83 of Q8N2G4 and also to amino acids 1 to 83 of R11723_PEA_1_P6. The first amino acid sequence and the sequence corresponding to amino acids 84 to 222 of R11723_PEA_1_P6: A polypeptide having at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95%, of a second amino acid sequence homologous to the polypeptide having VVLGFGRSHDPPPNLVGHPAYGQCHNNQPWADTSRRERQRKHSMRTQ; Provided is an isolated chimeric polypeptide encoding R11723_PEA_1_P6 in which the first and second amino acid sequences are in contiguous and sequential order.

  According to a preferred embodiment of the present invention, according to a preferred embodiment of the invention, according to a preferred embodiment of the invention An isolated polypeptide encoding the tail of R11723_PEA_1_P6, more preferably comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous To provide.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding R11723_PEA_1_P6, corresponding to amino acids 24 to 106 of BAC 85518 and corresponding to amino acids 1 to 83 of R11723_PEA_1_P6. The first amino acid sequence and the sequence corresponding to amino acids 84 to 222 of R11723_PEA_1_P6 SPCRGLAPGREEQRALHKAGAVGGGVRMYAQALLVVGVLQRQAAAQHLHEHPPKLLRGHRVQERVDDRAEVEKRLREGEEDHVRPE GPRPVVLGFGRSHDPPPNLVGHPAYGQCHNNQPWADTSRRERQRKHSMRTQ comprising a second amino acid sequence homologous to the polypeptide having at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95%. Provided is an isolated chimeric polypeptide encoding R11723_PEA_1_P6 in which the first and second amino acid sequences are in contiguous and sequential order.

  According to a preferred embodiment of the present invention, according to a preferred embodiment of the invention, according to a preferred embodiment of the invention An isolated polypeptide encoding the tail of R11723_PEA_1_P6, more preferably comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous To provide.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding R11723_PEA_1_P7, which corresponds to amino acids 1 to 64 of Q96AC2 and also to amino acids 1 to 64 of R11723_PEA_1_P7. At least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably a polypeptide having the first amino acid sequence and the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT corresponding to amino acids 65-93 of R11723_PEA_1_P7 Is at least 95% phase And a second amino acid sequence, wherein the first and second amino acid distribution is contiguous, and in sequential order, provides an isolated chimeric polypeptide coding R11723_PEA_1_P7.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of R11723_PEA_1_P7, comprising at least 70%, optionally at least about 80%, preferably at least about 85%, with the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT in R11723_PEA_1_P7 More preferably, provided is an isolated polypeptide encoding the tail of R11723_PEA_1_P7, comprising a polypeptide that is at least about 90%, and most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding R11723_PEA_1_P7, which corresponds to amino acids 1 to 64 of Q8N2G4 and also to amino acids 1 to 64 of R11723_PEA_1_P7. At least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably a polypeptide having the first amino acid sequence and the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT corresponding to amino acids 65-93 of R11723_PEA_1_P7 Is at least 95% phase And a second amino acid sequence, wherein the first and second amino acid distribution is contiguous, and in sequential order, provides an isolated chimeric polypeptide coding R11723_PEA_1_P7.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of R11723_PEA_1_P7, comprising at least 70%, optionally at least about 80%, preferably at least about 85%, with the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT in R11723_PEA_1_P7 More preferably, provided is an isolated polypeptide encoding the tail of R11723_PEA_1_P7, comprising a polypeptide that is at least about 90%, and most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding R11723_PEA_1_P7, comprising a polypeptide having the sequence MWVLG corresponding to amino acids 1 to 5 of R11723_PEA_1_P7, at least 70%, optionally at least 80% IAATFCGLFLPFLPAL QIQCYQCEEFQLNNDSSPEFIVNCNCTVNVQDMCQKEVMEQS corresponds to the first amino acid sequence which is preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous and corresponding to amino acids 22 to 80 of BAC 85 273 and also to amino acids 6 to 64 of R11723_PEA_1_P7. R11723_PEA_1_P7 with a second amino acid sequence at least 90% homologous to A third polypeptide having at least 70%, optionally at least 80%, preferably at least 85%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homology to the polypeptide having the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT corresponding to amino acids 65 to 93 The present invention provides an isolated chimeric polypeptide encoding R11723_PEA_1_P7, which comprises an amino acid sequence, and wherein the first, second and third amino acid sequences are adjacent and in sequential order.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tip of R11723_PEA_1_P7, comprising at least 70%, optionally at least about 80%, preferably at least about 85%, of the sequence MWVLG of R11723_PEA_1_P7 Provided is an isolated polypeptide encoding the tip of R11723_PEA_1_P7, which comprises a polypeptide that is preferably at least about 90%, and most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of R11723_PEA_1_P7, comprising at least 70%, optionally at least about 80%, preferably at least about 85%, with the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT in R11723_PEA_1_P7 More preferably, provided is an isolated polypeptide encoding the tail of R11723_PEA_1_P7, comprising a polypeptide that is at least about 90%, and most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding R11723_PEA_1_P7, corresponding to amino acids 24 to 87 of BAC 85518 and corresponding to amino acids 1 to 64 of R11723_PEA_1_P7. At least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably a polypeptide having the first amino acid sequence and the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT corresponding to amino acids 65-93 of R11723_PEA_1_P7 Is at least 9 % Phase and a same a second amino acid sequence, wherein the first and second amino acid distribution is contiguous, and in sequential order, provides an isolated chimeric polypeptide coding R11723_PEA_1_P7.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of R11723_PEA_1_P7, comprising at least 70%, optionally at least about 80%, preferably at least about 85%, with the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT in R11723_PEA_1_P7 More preferably, provided is an isolated polypeptide encoding the tail of R11723_PEA_1_P7, comprising a polypeptide that is at least about 90%, and most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding R11723_PEA_1_P13, which corresponds to amino acids 1 to 63 of Q96AC2 and also to amino acids 1 to 63 of R11723_PEA_1_P13. At least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably a polypeptide having the first amino acid sequence and the sequence DTKRTNTLLFEMRHFAKAKTT corresponding to amino acids 64-84 of R11723_PEA_1_P13 Is at least 95% homologous to the second And a acid sequence, wherein the first and second amino acid distribution is contiguous, and in sequential order, provides an isolated chimeric polypeptide coding R11723_PEA_1_P13.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of R11723_PEA_1_P13, which is at least 70%, optionally at least about 80%, preferably at least about 85%, with the sequence DTKRTNTLLFEMRHFAKQLTT in R11723_PEA_1_P13 More preferably, provided is an isolated polypeptide encoding the tail of R11723_PEA_1_P13, comprising a polypeptide that is at least about 90%, and most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding R11723_PEA_1_P10, which corresponds to amino acids 1 to 63 of Q96AC2 and also to amino acids 1 to 63 of R11723_PEA_1_P10. At least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably a polypeptide having the first amino acid sequence and the sequence DRVSLCHEAGVQWNNFSTLQPLPPRLK corresponding to amino acids 64-90 of R11723_PEA_1_P10 Is at least 95% phase And a second amino acid sequence, wherein the first and second amino acid distribution is contiguous, and in sequential order, provides an isolated chimeric polypeptide coding R11723_PEA_1_P10.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of R11723_PEA_1_P10, which is at least 70%, optionally at least about 80%, preferably at least about 85%, with the sequence DRVSLCHEAGVQWNNFSTLQPLPPRLK in R11723_PEA_1_P10 More preferably, provided is an isolated polypeptide encoding the tail of R11723_PEA_1_P10, comprising a polypeptide that is at least about 90%, and most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding R11723_PEA_1_P10, which corresponds to amino acids 1 to 63 of Q8N2G4 and also to amino acids 1 to 63 of R11723_PEA_1_P10. At least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably a polypeptide having the first amino acid sequence and the sequence DRVSLCHEAGVQWNNFSTLQPLPPRLK corresponding to amino acids 64-90 of R11723_PEA_1_P10 Is at least 95% phase And a second amino acid sequence, wherein the first and second amino acid distribution is contiguous, and in sequential order, provides an isolated chimeric polypeptide coding R11723_PEA_1_P10.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of R11723_PEA_1_P10, which is at least 70%, optionally at least about 80%, preferably at least about 85%, with the sequence DRVSLCHEAGVQWNNFSTLQPLPPRLK in R11723_PEA_1_P10 More preferably, provided is an isolated polypeptide encoding the tail of R11723_PEA_1_P10, comprising a polypeptide that is at least about 90%, and most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding R11723_PEA_1_P10, comprising a polypeptide having the sequence MWVLG corresponding to amino acids 1 to 5 of R11723_PEA_1_P10, at least 70%, optionally at least 80% IAATFCCLGLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMEQSA corresponds to the first amino acid sequence, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous and corresponding to amino acids 22 to 79 of BAC 85 273 and also to amino acids 6 to 63 of R11723_PEA_1_P10. A second amino acid sequence at least 90% homologous to A polypeptide having the sequence DRVSLCHEAGVQWNNFSTLQPLPPRLK corresponding to amino acids 64-90 of 10 at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous And an isolated chimeric polypeptide encoding R11723_PEA_1_P10, wherein the first, second and third amino acid sequences are adjacent and in sequential order.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tip of R11723_PEA_1_P10, wherein the sequence MWVLG of R11723_PEA_1_P10 and at least 70%, optionally at least about 80%, preferably at least about 85%, more Provided is an isolated polypeptide encoding the tip of R11723_PEA_1_P10, which comprises a polypeptide that is preferably at least about 90%, and most preferably at least about 95% homologous.

According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of R11723_PEA_1_P10, which is at least 70%, optionally at least about 80%, preferably at least about 85%, with the sequence DRVSLCHEAGVQWNNFSTLQPLPPRLK in R11723_PEA_1_P10 More preferably, provided is an isolated polypeptide encoding the tail of R11723_PEA_1_P10, comprising a polypeptide that is at least about 90%, and most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding R11723_PEA_1_P10, corresponding to amino acids 24 to 86 of BAC 85518 and corresponding to amino acids 1 to 63 of R11723_PEA_1_P10. At least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably a polypeptide having the first amino acid sequence and the sequence DRVSLCHEAGVQWNNFSTLQPLPPRLK corresponding to amino acids 64-90 of R11723_PEA_1_P10 Is at least 9 % Phase and a same a second amino acid sequence, wherein the first and second amino acid distribution is contiguous, and in sequential order, provides an isolated chimeric polypeptide coding R11723_PEA_1_P10.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of R11723_PEA_1_P10, which is at least 70%, optionally at least about 80%, preferably at least about 85%, with the sequence DRVSLCHEAGVQWNNFSTLQPLPPRLK in R11723_PEA_1_P10 More preferably, provided is an isolated polypeptide encoding the tail of R11723_PEA_1_P10, comprising a polypeptide that is at least about 90%, and most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, it is an isolated chimeric polypeptide encoding R16276_PEA_1_P7, which corresponds to amino acids 1 to 41 of NOV_HUMAN and also to amino acids 1 to 41 of R16276_PEA_1_P7 at least 90% homologous to MQSV CPATPPTCAPGPRA VLDGCSCCLCGARGGSCSDLEPCDESSGLYCDRSADPSNQTGICT corresponding to the first amino acid sequence and to the bridge amino acid Q corresponding to amino acid 42 of R16276_PEA_1_P7 and to amino acids 43 to 103 of NOV_HUMAN and also to amino acids 43 to 103 of R16276_PEA_1_P7 At least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, of a second amino acid sequence homologous and a polypeptide having the sequence GNPAPSDAV corresponding to amino acids 104 to 111 of R16276_PEA_1_P7. Most preferably, it comprises at least a 95% homologous third amino acid sequence, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence, and third amino acid sequence are adjacent and in sequential order Provided is an isolated chimeric polypeptide encoding R16276_PEA_1_P7.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of R16276_PEA_1_P7, comprising at least 70%, optionally at least about 80%, preferably at least about 85%, of the sequence GNPAPSAV in R16276_PEA_1_P7 More preferably, provided is an isolated polypeptide encoding the tail of R16276_PEA_1_P7, comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, it is an isolated chimeric polypeptide encoding R16276_PEA_1_P7, which corresponds to amino acids 1 to 41 of NOV_HUMAN and also to amino acids 1 to 41 of R16276_PEA_1_P7 at least 90% homologous to MQSV CPATPPTCAPGPRA VLDGCSCCLCGARGGSCSDLEPCDESSGLYCDRSADPSNQTGICT corresponding to the first amino acid sequence and to the bridge amino acid Q corresponding to amino acid 42 of R16276_PEA_1_P7 and to amino acids 43 to 103 of NOV_HUMAN and also to amino acids 43 to 103 of R16276_PEA_1_P7 At least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, of a second amino acid sequence homologous and a polypeptide having the sequence GNPAPSDAV corresponding to amino acids 104 to 111 of R16276_PEA_1_P7. Most preferably, it comprises at least a 95% homologous third amino acid sequence, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence, and third amino acid sequence are adjacent and in sequential order Provided is an isolated chimeric polypeptide encoding R16276_PEA_1_P7.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of R16276_PEA_1_P7, comprising at least 70%, optionally at least about 80%, preferably at least about 85%, of the sequence GNPAPSAV in R16276_PEA_1_P7 More preferably, provided is an isolated polypeptide encoding the tail of R16276_PEA_1_P7, comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding HUMCEA_PEA_1_P4, corresponding to amino acids 1-234 of CEA5_HUMAN, corresponding to amino acids 1-234 of HUMCEA_PEA_1_P4 MESPSAPPHRWCIPWQRLLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLVHNLPQHLFGYSWYKGERVDGNRQIIGYVIGTQQATPGPAYSGREIIYPNASLLIQNIIQNDTGFYTLHVIKSDLVNEEATGQFRVYPELPKPSISSNNSKPVEDKDAVAFTCEPETQDATYLWWVNNQSLPVSPRLQLSNGNRTLTLFNVTRNDTASYKCETQNPVSA A polypeptide having a first amino acid sequence which is at least 90% homologous to RSDSVILNVL and a sequence corresponding to amino acids 235 to 315 of HUMCEA_PEA_1_P4 CEYICSSLAQAASPNPQGQRQDFSVPLRFY TDPQPWTSRLSVTFCRTKDRTG NRAGGAASVLGGSGSTPYDGRNR and at least 70%, preferably at least 80%, preferably at least 80% Comprises HUMCEA_PEA_1_P4, which comprises a second amino acid sequence which is at least 90%, most preferably at least 95% homologous, said first amino acid sequence and the second amino acid sequence being adjacent and in sequential order An isolated chimeric polypeptide is provided.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of HUMCEA_PEA_1_P4, wherein at least 70%, preferably at least 70%, preferably at least 70%. More preferably, provided is an isolated polypeptide encoding the tail of HUMCEA_PEA_1_P4, comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding HUMCEA_PEA_1_P5, corresponding to amino acids 1-675 of CEA5_HUMAN, corresponding to amino acids 1-675 of HUMCEA_PEA_1_P5 MESPSAPPHRWCIPWQRLLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLVHNLPQHLFGYSWYKGERVDGNRQIIGYVIGTQQATPGPAYSGREIIYPNASLLIQNIIQNDTGFYTLHVIKSDLVNEEATGQFRVYPELPKPSISSNNSKPVEDKDAVAFTCEPETQDATYLWWVNNQSLPVSPRLQLSNGNRTLTLFNVTRNDTASYKCETQNPVSA RSDSVILNVLYGPDAPTISPLNTSYRSGENLNLSCHAASNPPAQYSWFVNGTFQQSTQELFIPNITVNNSGSYTCQAHNSDTGLNRTTVTTITVYAEPPKPFITSNNSNPVEDEDAVALTCEPEIQNTTYLWWVNNQSLPVSPRLQLSNDNRTLTLLSVTRNDVGPYECGIQNELSVDHSDPVILNVLYGPDDPTISPSYTYYRPGVNLSLSCHAASNPPAQYSWLIDGNIQQHTQELFISNITEKNSGLYTCQANNSASGHSRTTVKTITVSAELPKPSISSNNSKPVEDKDAVAFTCEPEAQNTTYLWWVNGQSLPVSPRLQLSNGNRTL The LIFH s s s s s s s s s s s s sssssssssssssssssss a required amino acid sequence of at least 90% homology with the 1st amino acid sequence and a HUMCEA_PEA5_ P5 Comprises a second amino acid sequence which is at least 90%, most preferably at least 95% homologous, said first amino acid sequence and the second amino acid sequence Provided is an isolated chimeric polypeptide encoding HUMCEA_PEA_1_P5, wherein the amino acid sequences are in contiguous and sequential order.

  According to a preferred embodiment of the invention, an isolated polypeptide encoding the tail of HUMCEA_PEA_1_P5, which is at least 70%, optionally at least about 80%, preferably at least about 85%, with the sequence GKWLPGASASYSGVESIWFSPKSQEDFFPSLCSMGTRKSQILS in the sequence HUMCEA_PEA_1_P5 More preferably, provided is an isolated polypeptide encoding the tail of HUMCEA_PEA_1_P5, comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding HUMCEA_PEA_1_P19, corresponding to amino acids 1-232 of CEA5_HUMAN, corresponding to amino acids 1-232 of HUMCEA_PEA_1_P19 MESPSAPPHRWCIPWQRLLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLVHNLPQHLFGYSWYKGERVDGNRQIIGYVIGTQQATPGPAYSGREIIYPNASLLIQNIIQNDTGFYTLHVIKSDLVNEEATGQFRVYPELPKPSISSNNSKPVEDKDAVAFTCEPETQDATYLWWVNNQSLPVSPRLQLSNGNRTLTLFNVTRNDTASYKCETQNPV ARLYSDSVILN is a first amino acid sequence that is at least 90% homologous to ARRS SDS VILN and corresponds to amino acids 589-702 of CEA5_HUMAN and also corresponds to amino acids 233-346 of HUMCEA_PEA_1_P19. Provided is an isolated chimeric polypeptide encoding HUMCEA_PEA_1_P19, wherein the first and second amino acid sequences are adjacent and in sequential order.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding the edge portion of HUMCEA_PEA_1_P19, having a length “n”, wherein n is at least about 10 amino acids long, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length, most preferably at least about 50 amino acids in length), wherein at least two amino acids comprise NV and have the following structure: A polypeptide having a sequence beginning with any of the numbers 232-x-232 and ending with the amino acid number 233 + ((n-2) -x), wherein x varies from 0 to n-2 Provided is an isolated chimeric polypeptide encoding an edge portion of HUMCEA_PEA_1_P19.

  A MELPTUS JET JPG JUT is a JCH, which is the isolated chimeric polypeptide coding for HUMC. This is an isolated chimeric polypeptide coding for HUMC. The first amino acid sequence corresponds to amino acids 499-702 of CEA5_HUMAN and to amino acids 143-346 of HUMCEA_PEA_1_P20 And a corresponding ELPKPSISSNNSKPVEDKDAVAFTCEPEAQNTTYLWWVNGQSLPVSPRLQLSNGNRTLTLFNVTRNDARAYVCGIQNSVSANRSDPVTLDVLYGPDTPIISPPDSSYLSGANLNLSCHSASNPSPQYSWRINGIPQQHTQVLFIAKITPNNNGTYACFVSNLATGRNNSIVKSITVSASGTSPGLSAGATVGIMIGVLVGVALI at least 90% homologous second amino acid sequence, the first amino acid sequence and a second amino acid sequence, contiguous and in sequential order, isolated chimera encoding HUMCEA_PEA_1_P20 Provided is a polypeptide.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding the edge portion of HUMCEA_PEA_1_P20, having a length “n”, wherein n is at least about 10 amino acids long, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length, most preferably at least about 50 amino acids in length), wherein at least two amino acids comprise PE; A polypeptide having a sequence beginning with any of the numbers 142-x to 142 and ending with the amino acid number 143 + ((n-2) -x), wherein x varies from 0 to n-2 Provided is an isolated chimeric polypeptide encoding an edge portion of HUMCEA_PEA_1_P20.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding Z44808_PEA_1_P5, corresponding to amino acids 1-441 of SMO2_HUMAN, corresponding to amino acids 1-441 of Z44808_PEA_1_P5 MLLPQLCWLPLLAGLLPPVPAQKFSALTFLRVDQDKDKDCSLDCAGSPQKPLCASDGRTFLSRCEFQRAKCKDPQLEIAYRGNCKDVSRCVAERKYTQEQARKEFQQVFIPECNDDGTYSQVQCHSYTGYCWCVTPNGRPISGTAVAHKTPRCPGSVNEKLPQREGTGKTDDAAAPALETQPQGDEEDIASRYPTLWTEQVKSRQNKTNKNSVSSCDQEHQSA A first amino acid sequence at least 90% homologous to IieikeikyuPikeienudienubuibuiaipiishieieichijijieruwaikeiPibuikyushieichiPiesutijiwaishidaburyushibuierubuiditijiaruPiaiPijitiesutiaruwaiikyuPikeishidienutieiarueieichiPieikeieiarudieruwaikeijiarukyuerukyujishiPijieikeikeieichiiefuerutiesubuierudieieruesutidiemubuieichieieiesudiPiesuesuesuesujiarueruesuiPidiPiesueichitieruiiarubuibuieichidaburyuwaiefukeieruerudikeienuesuesujidiaijikeikeiiaikeiPiefukeiaruefueruarukeikeiesukeiPikeikeishibuikeikeiefubuiiwaishidibuienuenudikeiesuaiesubuikyuieruemujishierujibuieiKEDGKADTKKRHTPRGHAESTSNRQ, polypeptide at least 70% with a sequence corresponding to DAMVVSSRPKATTHRKSRTLSRR to amino acid 442-464 of Z44808_PEA_1_P5, optionally at least 80%, Preferably, it comprises a second amino acid sequence which is at least 85%, more preferably at least 90%, most preferably at least 95% homologous, said first and second amino acid sequences being adjacent and in a consecutive order Provided is an isolated chimeric polypeptide encoding Z44808_PEA_1_P5.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of Z44808_PEA_1_P5, comprising at least 70%, optionally at least about 80%, preferably at least about 85%, of the sequence DAMVVSsRPKATTHRKSRTLSRR in Z44808_PEA_1_P5 More preferably, provided is an isolated polypeptide encoding the tail of Z44808_PEA_1_P5, comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding Z44808_PEA_1_P6, corresponding to amino acids 1-428 of SMO2_HUMAN, corresponding to amino acids 1-428 of Z44808_PEA_1_P6 MLLPQLCWLPLLAGLLPPVPAQKFSALTFLRVDQDKDKDCSLDCAGSPQKPLCASDGRTFLSRCEFQRAKCKDPQLEIAYRGNCKDVSRCVAERKYTQEQARKEFQQVFIPECNDDGTYSQVQCHSYTGYCWCVTPNGRPISGTAVAHKTPRCPGSVNEKLPQREGTGKTDDAAAPALETQPQGDEEDIASRYPTLWTEQVKSRQNKTNKNSVSSCDQEHQSA A first amino acid sequence at least 90% homologous to IieikeikyuPikeienudienubuibuiaipiishieieichijijieruwaikeiPibuikyushieichiPiesutijiwaishidaburyushibuierubuiditijiaruPiaiPijitiesutiaruwaiikyuPikeishidienutieiarueieichiPieikeieiarudieruwaikeijiarukyuerukyujishiPijieikeikeieichiiefuerutiesubuierudieieruesutidiemubuieichieieiesudiPiesuesuesuesujiarueruesuiPidiPiesueichitieruiiarubuibuieichidaburyuwaiefukeieruerudikeienuesuesujidiaijikeikeiiaikeiPiefukeiaruefueruarukeikeiesukeiPikeikeishibuikeikeiefubuiiwaishidibuienuenudikeiesuISVQELMGCLGVAKEDGKADTKKRH, polypeptide at least 70% with a sequence corresponding to RSKRNL to amino acid 429-434 of Z44808_PEA_1_P6, optionally at least 80%, preferably at least 85%, more Preferably at least 90%, An isolated chimeric polypeptide encoding Z44808_PEA_1_P6, preferably also comprising a second amino acid sequence which is at least 95% homologous, said first and second amino acid sequences being adjacent and in sequential order .

  According to a preferred embodiment of the invention, an isolated polypeptide encoding the tail of Z44808_PEA_1_P6, comprising at least 70%, optionally at least about 80%, preferably at least about 85%, of the sequence RSKRNL in Z44808_PEA_1_P6 More preferably, provided is an isolated polypeptide encoding the tail of Z44808_PEA_1_P6, comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding Z44808_PEA_1_P7, corresponding to amino acids 1-441 of SMO2_HUMAN, corresponding to amino acids 1-441 of Z44808_PEA_1_P7 MLLPQLCWLPLLAGLLPPVPAQKFSALTFLRVDQDKDKDCSLDCAGSPQKPLCASDGRTFLSRCEFQRAKCKDPQLEIAYRGNCKDVSRCVAERKYTQEQARKEFQQVFIPECNDDGTYSQVQCHSYTGYCWCVTPNGRPISGTAVAHKTPRCPGSVNEKLPQREGTGKTDDAAAPALETQPQGDEEDIASRYPTLWTEQVKSRQNKTNKNSVSSCDQEHQSA A first amino acid sequence at least 90% homologous to IieikeikyuPikeienudienubuibuiaipiishieieichijijieruwaikeiPibuikyushieichiPiesutijiwaishidaburyushibuierubuiditijiaruPiaiPijitiesutiaruwaiikyuPikeishidienutieiarueieichiPieikeieiarudieruwaikeijiarukyuerukyujishiPijieikeikeieichiiefuerutiesubuierudieieruesutidiemubuieichieieiesudiPiesuesuesuesujiarueruesuiPidiPiesueichitieruiiarubuibuieichidaburyuwaiefukeieruerudikeienuesuesujidiaijikeikeiiaikeiPiefukeiaruefueruarukeikeiesukeiPikeikeishibuikeikeiefubuiiwaishidibuienuenudikeiesuaiesubuikyuieruemujishierujibuieiKEDGKADTKKRHTPRGHAESTSNRQ, polypeptide at least 70% with a sequence corresponding to LLWLRGKVSFYCF to amino acid 442-454 of Z44808_PEA_1_P7, optionally at least 80%, preferably at least Z44808_PEA_1_P7 comprising a second amino acid sequence that is 5%, more preferably at least 90%, most preferably at least 95% homologous, said first and second amino acid sequences being in a contiguous and consecutive order Provided is an isolated chimeric polypeptide that encodes.

  According to a preferred embodiment of the invention, an isolated polypeptide encoding the tail of Z44808_PEA_1_P7, comprising at least 70%, optionally at least about 80%, preferably at least about 85% of the sequence LLWLRGKVSFYCF in Z44808_PEA_1_P7. More preferably, provided is an isolated polypeptide encoding the tail of Z44808_PEA_1_P7, comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding Z44808_PEA_1_P11, it corresponds to amino acids 1 - 170 of SMO2_HUMAN, at least 90% homologous I and MLLPQLCWLPLLAGLLPPVPAQKFSALTFLRVDQDKDKDCSLDCAGSPQKPLCASDGRTFLSRCEFQRAKCKDPQLEIAYRGNCKDVSRCVAERKYTQEQARKEFQQVFIPECNDDGTYSQVQCHSYTGYCWCVTPNGRPISGTAVAHKTPRCPGSVNEKLPQREGTGKT corresponding to amino acids 1 - 170 of Z44808_PEA_1_P11 The first amino acid sequence corresponds to amino acids 188 to 446 of SMO2_HUMAN, Z Also amino acids 171-429 of 4808_PEA_1_P11 and a corresponding DIASRYPTLWTEQVKSRQNKTNKNSVSSCDQEHQSALEEAKQPKNDNVVIPECAHGGLYKPVQCHPSTGYCWCVLVDTGRPIPGTSTRYEQPKCDNTARAHPAKARDLYKGRQLQGCPGAKKHEFLTSVLDALSTDMVHAASDPSSSSGRLSEPDPSHTLEERVVHWYFKLLDKNSSGDIGKKEIKPFKRFLRKKSKPKKCVKKFVEYCDVNNDKSISVQELMGCLGVAKEDGKADTKKRHTPRGHAESTSNRQPRKQG at least 90% homologous second amino acid sequence, wherein the first and second amino acid distribution , Adjacent, and in sequential order, provides an isolated chimeric polypeptide coding Z44808_PEA_1_P11.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding the edge portion of Z44808_PEA_1_P11, having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length, most preferably at least about 50 amino acids in length), wherein at least two amino acids comprise TD and have the following structure: A polypeptide having a sequence beginning with any of the numbers 170-x to 170 and ending with the amino acid number 171 + ((n-2)-x), wherein x varies from 0 to n-2 Provided is an isolated chimeric polypeptide encoding the edge portion of Z44808_PEA_1_P11, including.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding H61775_P16, corresponding to amino acids 11 to 93 of Q9P2J2 and corresponding to amino acids 1 to 83 of H61775_P16. At least 70%, optionally at least 80%, with a polypeptide having the first amino acid sequence and the sequence DCGFPAFRELKRAETEVSPFFTFRTRICIWEDLKSTSFSPAGGRPPGGG PRTQEDSGLPCCWSRSSTLQV corresponding to amino acids 84-152 of H61775_P16, optionally at least 80%, Preferably, it comprises a second amino acid sequence which is at least 85%, more preferably at least 90%, most preferably at least 95% homologous, said first and second amino acid sequences being adjacent and in a consecutive order Provided is an isolated chimeric polypeptide encoding H61775_P16.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of H61775_P16, which is at least 70%, optionally at least about 80%, preferably at least about 85%, with the sequence DCGFPAFRELKRAETEVPVPFFTRRCIWEDLKSTGFSPAGGGRPPGGGPRTQEDSGPCPCRSSCSVTLQV in H61775_P16 Provided is an isolated polypeptide encoding the tail of H61775_P16, more preferably comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding H61775_P16, corresponding to amino acids 1 to 83 of AAQ 88495 and also corresponding to amino acids 1 to 83 of H61775_P16, is at least 90% homologous to A polypeptide having at least 70%, optionally at least 80% with a polypeptide having the first amino acid sequence and the sequence DCGFPAFRELKRAETEVSPFFTFRTRICIWEDLKSTGFSPAGGGRPPGGGPRTQEDSGLPCCWSRSSTLQV corresponding to amino acids 84-152 of H61775_P16 Preferably, it comprises a second amino acid sequence which is at least 85%, more preferably at least 90%, most preferably at least 95% homologous, said first and second amino acid sequences being adjacent and in sequential order , Provides an isolated chimeric polypeptide encoding H61775_P16.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of H61775_P16, which is at least 70%, optionally at least about 80%, preferably at least about 85%, with the sequence DCGFPAFRELKRAETEVPVPFFTRRCIWEDLKSTGFSPAGGGRPPGGGPRTQEDSGPCPCRSSCSVTLQV in H61775_P16 Provided is an isolated polypeptide encoding the tail of H61775_P16, more preferably comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding H61775_P17, corresponding to amino acids 11 to 93 of Q9P2J2 and corresponding to amino acids 1 to 83 of H61775_P17. Provided is an isolated chimeric polypeptide encoding H61775_P17, which comprises a first amino acid sequence.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding H61775_P17, corresponding to amino acids 1 to 83 of AAQ 88495 and also corresponding to amino acids 1 to 83 of H61775_P17, is at least 90% homologous to Provided is an isolated chimeric polypeptide encoding H61775_P17, which comprises a first amino acid sequence.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding M85491_PEA_1_P13, corresponding to amino acids 1-476 of EPB2_HUMAN, corresponding to amino acids 1-476 of M85491_PEA_1_P13 MALRRLGAALLLLPLLAAVEETLMDSTTATAELGWMVHPPSGWEEVSGYDENMNTIRTYQVCNVFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCSSIPSVPGSCKETFNLYYYEADFDSATKTFPNWMENPWVKVDTIAADESFSQVDLGGRVMKINTEVRSFGPVSRSGFYLAFQDYGGCMSLIAVRVFYRKCPRIIQNGAIFQETLSGAESTSLVA The first amino acid sequence at least 90% homologous to ArujiesushiaieienueiiibuidibuiPiaikeieruwaishienujidijiidaburyuerubuiPiaijiarushiemushikeieijiefuieibuiienujitibuishiarujishiPiesujitiefukeieienukyujidiieishitieichishiPiaienuesuarutitiesuijieitienushibuishiaruenujiwaiwaiarueidierudiPierudiemuPishititiaiPiesueiPikyueibuiaiesuesubuienuitiesueruemueruidaburyutiPiPiarudiesujijiaruidierubuiwaienuaiaishikeiesushijiesujiarujieishitiarushijidienubuikyuwaieiPiarukyuerujierutiiPiaruaiwaiaiesudieruerueieichitikyuwaitiefuiaikyueibuienujibuitidikyuesuPiefuesuPikyuefueiesubuienuaititienukyueieiPiesueibuiesuaiemueichikyubuiesuarutibuidiesuITLSWSQPDQPNGVILDYELQYYEK, sequence VPIGWVLSPSPTSLRAPLPG corresponding to amino acids 477-496 of M85491_PEA_1_P13 A first amino acid sequence having at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homology to the polypeptide having Provided is an isolated chimeric polypeptide encoding M85491_PEA_1_P13, wherein the second amino acid sequence is in a contiguous and sequential order.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of M85491_PEA_1_P13, comprising at least 70%, optionally at least about 80%, preferably at least about 85%, of the sequence VPIGWVLSPSPTSLRAPLPG in M85491_PEA_1_P13 More preferably, an isolated polypeptide encoding a tail of at least about 90%, most preferably at least about 95% homologous polypeptide is provided.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding M85491_PEA_1_P14, corresponding to amino acids 1-270 of EPB2_HUMAN, corresponding to amino acids 1-270 of M85491_PEA_1_P14 MALRRLGAALLLLPLLAAVEETLMDSTTATAELGWMVHPPSGWEEVSGYDENMNTIRTYQVCNVFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCSSIPSVPGSCKETFNLYYYEADFDSATKTFPNWMENPWVKVDTIAADESFSQVDLGGRVMKINTEVRSFGPVSRSGFYLAFQDYGGCMSLIAVRVFYRKCPRIIQNGAIFQETLSGAESTSLVA A polypeptide having at least 70%, optionally at least 80%, preferably at least 85%, preferably having a first amino acid sequence at least 90% homologous to RGSCIANAEEVDVPIKLYCNGDGEWLVPIGRCMCKAGFEAVENGTVCR and the sequence ERQDLTMLSRLVLSNSWPQMILPPPQPPKVLEL corresponding to amino acids 271 to 301 of M85491_PEA_1_P14 Is an isolated chimera encoding M85491_PEA_1_P14, comprising a second amino acid sequence which is at least 90%, most preferably at least 95% homologous, said first and second amino acid sequences being adjacent and in sequential order Provided is a polypeptide.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of M85491_PEA_1_P14, comprising at least 70%, optionally at least about 80%, preferably at least about 85%, of the sequence ERQDLTMLRSRLVLNSSWQMIPPPPPPKVLEL in M85491_PEA_1_P14 More preferably, provided is an isolated polypeptide encoding the tail of M85491_PEA_1_P14, comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding T39971_P6, corresponding to amino acids 1-276 of VTNC_HUMAN, corresponding to amino acids 1-276 of T39971_P6 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAECKPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGVL And a polypeptide having a sequence of TQGVVGD corresponding to amino acids 277 to 283 of T39971_P6, at least 70%, optionally at least 80%, preferably at least 85%, more preferably a first amino acid sequence at least 90% homologous to PDYPRNISDDGFD. Is an isolated chimera encoding T39971_P6, comprising a second amino acid sequence which is at least 90%, most preferably at least 95% homologous, said first and second amino acid sequences being in a contiguous and sequential order Provided is a polypeptide.

  According to a preferred embodiment of the invention, an isolated polypeptide encoding the tail of T39971_P6, which is at least 70%, optionally at least about 80%, preferably at least about 85%, with the sequence TQGVVGD in T39971_P6. More preferably, provided is an isolated polypeptide encoding the tail of T39971_P6, comprising a polypeptide that is at least about 90%, and most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding T39971_P9, corresponding to amino acids 1-325 of VTNC_HUMAN, corresponding to amino acids 1-325 of T39971_P9 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAECKPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGVL The first amino acid sequence at least 90% homologous to PidiwaiPiaruenuaiesudijiefudijiaiPidienubuidieieierueieruPieieichiesuwaiesujiaruiarubuiwaiefuefukeijikeikyuwaidaburyuiwaikyuefukyueichikyuPiesukyuiishiijiesuesueruesueiVFEHFAMMQRDSWEDIFELLFWGRT, corresponding to amino acids 357-478 of VTNC_HUMAN, and a corresponding SGMAPRPSLAKKQRFRHRNRKGYRSQRGHSRGRNQNSRRPSRATWLSLFSSEESNLGANNYDDYRMDWLVPATCEPIQSVFFFSGDKYYRVNLRTRRVDTVDPPYPRSIAQYWLGCPAPGHL at least 90% homologous second amino acid sequence to amino acids 326-447 of T39971_P9, The first and second amino acid sequences are adjacent to each other And, and in sequential order, it provides an isolated chimeric polypeptide coding T39971_P9.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding the rim portion of T39971_P9, having a length "n", wherein n is at least about 10 amino acids long, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length, most preferably at least about 50 amino acids in length), wherein at least two amino acids comprise TS and have the following structure: A polypeptide having a sequence beginning with any of the numbers 325-x to 325 and ending with the amino acid number 326 + ((n-2) -x), wherein x varies from 0 to n-2 Provided is an isolated chimeric polypeptide encoding the edge portion of T39971_P9, including:

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding T39971_P11, corresponding to amino acids 1-326 of VTNC_HUMAN, corresponding to amino acids 1-326 of T39971_P11 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAECKPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDG LQDQ with a first amino acid sequence that is at least 90% homologous to the first amino acid sequence of at least 90% homologous to the TPNC_HUMAN and also to the amino acids 327-363 of the T 399 71 _ P 11 The present invention provides an isolated chimeric polypeptide encoding T39971_P11, wherein the first and second amino acid sequences are adjacent and in sequential order.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding the edge portion of T39971_P11, which has a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length, most preferably at least about 50 amino acids in length), wherein at least two amino acids comprise SD and have the following structure: A polypeptide having a sequence beginning with any of the numbers 326-x to 326 and ending at the amino acid number 327 + ((n-2) -x), wherein x varies from 0 to n-2. Provided is an isolated chimeric polypeptide encoding the edge portion of T39971_P11, including:

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding T39971_P11, corresponding to amino acids 1-326 of Q9BSH7, corresponding to amino acids 1-326 of T39971_P11 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAECKPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGVLDP The first amino acid sequence at least 90% homologous to WaiPiaruenuaiesudijiefudijiaiPidienubuidieieierueieruPieieichiesuwaiesujiaruiarubuiwaiefuefukeijikeikyuwaidaburyuiwaikyuefukyueichikyuPiesukyuiishiijiesuesueruesueibuiFEHFAMMQRDSWEDIFELLFWGRTS, corresponding to amino acids 442-478 of Q9BSH7, and a corresponding DKYYRVNLRTRRVDTVDPPYPRSIAQYWLGCPAPGHL at least 90% homologous second amino acid sequence to amino acids 327-363 of T39971_P11, The present invention provides an isolated chimeric polypeptide encoding T39971_P11, wherein the first and second amino acid sequences are adjacent and in sequential order.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding the edge portion of T39971_P11, which has a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length, most preferably at least about 50 amino acids in length), wherein at least two amino acids comprise SD and have the following structure: A polypeptide having a sequence beginning with any of the numbers 326-x to 326 and ending at the amino acid number 327 + ((n-2) -x), wherein x varies from 0 to n-2. Provided is an isolated chimeric polypeptide encoding the edge portion of T39971_P11, including:

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding T39971_P12, corresponding to amino acids 1-223 of VTNC_HUMAN, MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAECKPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKTYLFK at least 90% homologous to corresponding to amino acids 1-223 of T39971_P12 At least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably a polypeptide having the sequence VPGAVGQGRKHLGRV corresponding to amino acids 224 to 238 of T39971_P12. An isolated chimeric polypeptide encoding T39971_P12 is provided, which comprises a second amino acid sequence which is preferably at least 95% homologous, said first and second amino acid sequences being adjacent and in sequential order.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of T39971_P12, comprising at least 70%, optionally at least about 80%, preferably at least about 85% of the sequence VPGAVGQGRKHLGRV in T39971_P12. Provided is an isolated polypeptide encoding the tail of T39971_P12, more preferably comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding T39971_P12, corresponding to amino acids 1-223 of Q9BSH7, at least 90% homologous with the corresponding MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAECKPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKTYLFK to amino acids 1-223 of T39971_P12 First At least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% of the amino acid sequence and a polypeptide having the sequence VPGAVGQGRKHLGRV corresponding to amino acids 224 to 238 of T39971_P12 An isolated chimeric polypeptide encoding T39971_P12, which comprises a% homologous second amino acid sequence, wherein the first and second amino acid sequences are adjacent and in sequential order.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of T39971_P12, comprising at least 70%, optionally at least about 80%, preferably at least about 85% of the sequence VPGAVGQGRKHLGRV in T39971_P12. Provided is an isolated polypeptide encoding the tail of T39971_P12, more preferably comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding Z21368_PEA_1_P2, corresponding to amino acids 1-761 of SUL1_HUMAN, corresponding to amino acids 1-761 of Z21368_PEA_1_P2 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSLQVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESINYFKMSKRMYPHRPVMMVISHAA HGPEDSAPQFSKLYPNASQHITPSYNYAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNMLVETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEPGSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLPKYERVKELCQQARYQTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYARGFHDKDKECSCRESGYRASRSQRKSQRQFLRNQGTPKYKPRFVHTRQTRSLSVEFEGEIYD A first amino acid sequence at least 90% homologous to EnueruiiiiierukyubuierukyuPiaruenuaieikeiarueichidiijieichikeiJipiarudierukyueiesuesujijienuarujiaruemuerueidiesuesuenueibuiJipiPititibuiarubuitieichikeishiefuaieruPienudiesuaieichishiiaruieruwaikyuesueiarueidaburyukeidieichikeieiwaiaidikeiiaiieierukyudikeiaikeienueruaruibuiarujieichierukeiaruarukeiPiiishiesushiesukeikyuesuwaiwaienukeiikeijibuikeikeikyuikeierukeiesueichierueichiPiefukeiieieikyuibuidiesukeierukyueruefukeiienuenuaruaruarukeikeiiarukeiikeiaruarukyuarukeijiEECSLPGLTCFTHDNNHWQTAPFWN, at least 70% with a polypeptide having a sequence corresponding to PHKYSAHGRTRHFESATRTTNGAQKLSRI to amino acid 762-790 of Z21368_PEA_1_P2, optionally at least 80%, preferably less Z21368_PEA_1_P2 comprising a second amino acid sequence both 85%, more preferably at least 90%, most preferably at least 95% homologous, said first and second amino acid sequences being adjacent and in sequential order An isolated chimeric polypeptide encoding

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of Z21368_PEA_1_P2, comprising at least 70%, optionally at least about 80%, preferably at least about 85%, of the sequence PHKYSAHGRTRHFESATRTTNGAQKLSRI in Z21368_PEA_1_P2 More preferably, provided is an isolated polypeptide encoding the tail of Z21368_PEA_1_P2, comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, it is an isolated chimeric polypeptide encoding Z21368_PEA_1_P5, which is at least 90% homologous to MKYSCCALVLGLTLGSCSTVRSPRFRIQQERKNIRPNIILVLTDDQDVEL corresponding to amino acids 1 to 57 of Q7Z2W2 and also to amino acids 1 to 57 of Z21368_PEA_1_P5. The first amino acid sequence, the second cross-linked amino acid sequence including A, and the corresponding amino acids 139-871 of Q7Z2W2 and the corresponding amino acids 59-791 of Z21368_PEA_1_P5 MVISHAAPHGPEDSAPQFSKLYPNASQHITPSYNYAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNMLVETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEPGSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLPKYERVKELCQQARYQTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYARGFHDKDKECSCRESGYRASRSQRKSQRQFLRNQGTPKYKPRFVHTRQTRSLSV At least 90% homologous with the FEGEIYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLADSSNAVGPPTTVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEIEALQDKIKNLREVRGHLKRRKPEECSCSKQSYYNKEKGVKKQEKLKSHLHPFKEAAQEVDSKLQLFKENNRRRKKERKEKRRQRKGEECSLPGLTCFTHDNNHWQTAPFWNLGSFCACTSSNNNTYWCLRTVNETHNFLFCEFATGFLEYFDMNTDPYQLTNTVHTVERGILNQLHVQLMELRSCQGYKQCNPRPKNLDVGNKDGGSYDLHRGQLWDGWEG And an isolated chimeric polypeptide encoding Z21368_PEA_1_P5, wherein the first, second and third amino acid sequences are adjacent and in sequential order.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the edge portion of Z21368_PEA_1_P5, having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 Preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise LAF and have the following structure (Z21368_PEA_1_P5) Corresponding numbering): A sequence beginning with any of the amino acid numbers 57-x to 57 and ending with amino acid number 59 + ((n-2) -x), where x varies from 0 to n-2 And an isolated polypeptide encoding an edge portion of the polypeptide, including the polypeptide.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding Z21368_PEA_1_P5, corresponding to amino acids 1-751 of Z21368_PEA_1_P5 sequence MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELAFFGKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESINYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYNYAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNMLVETGELENTYIIYTADHGYHIGQFGLV GKSMPYDFDIRVPFFIRGPSVEPGSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLPKYERVKELCQQARYQTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYARGFHDKDKECSCRESGYRASRSQRKSQRQFLRNQGTPKYKPRFVHTRQTRSLSVEFEGEIYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLADSSNAVGPPTTVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEIEALQDKIKNL --------------------EVEVHHLHLRKRRKR PEECSCSQQS ck NQQQQQQQ ck ck. LRSCQGYKQCNPRP corresponding to 40 to 40 and also corresponding to amino acids 752 to 791 of Z21368_PEA_1_P5 An isolated chimeric polypeptide encoding Z21368_PEA_1_P5, comprising a second amino acid sequence that is at least 90% homologous to KNLDVGNKDGGSYDLHRGQLWDGWEG, wherein said first and second amino acid sequences are in contiguous and sequential order.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoded by the tip of Z21368_PEA_1_P5, sequences Z21368_PEA_1_P5 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELAFFGKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESINYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYNYAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNMLVETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVP FIRGPSVEPGSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLPKYERVKELCQQARYQTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYARGFHDKDKECSCRESGYRASRSQRKSQRQFLRNQGTPKYKPRFVHTRQTRSLSVEFEGEIYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLADSSNAVGPPTTVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEIEALQDKIKNLREVRGHLKRRKPEE A part of a part of the subject is at least a part of the lower part of the end of the subject is at the end of the lower part at the end of the lower part at the end of the lower part at the lower part of the lower part is at the end of the lower part at the lower part of the lower part at the end of the lower part of the lower part of the lower part of the lower part of the lower part of the lower part of the lower part; Provided is an isolated polypeptide.

  According to a preferred embodiment of the present invention, it is an isolated chimeric polypeptide encoding Z21368_PEA_1_P5, which is at least 90% homologous to MKYSCCALVLGLTLGSCSTVRSPRFRIQQERKNIRPNIILVLTDDQDVEL corresponding to amino acids 1-57 of SUL1_HUMAN and also corresponding to amino acids 1-57 of Z21368_PEA_1_P5. The first amino acid sequence corresponds to amino acids 138-871 of SUL1_HUMAN and also corresponds to amino acids 58-791 of Z21368_PEA_1_P5. HGPEDSAPQFSKLYPNASQHITPSYNYAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNMLVETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEPGSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLPKYERVKELCQQARYQTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYARGFHDKDKECSCRESGYRASRSQRKSQRQFLRNQGTPKYKPRFVHTRQTRSLSVEFEGEIYD At least 90% homologous second amino acid and NLEEEEELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLADSSNAVGPPTTVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEIEALQDKIKNLREVRGHLKRRKPEECSCSKQSYYNKEKGVKKQEKLKSHLHPFKEAAQEVDSKLQLFKENNRRRKKERKEKRRQRKGEECSLPGLTCFTHDNNHWQTAPFWNLGSFCACTSSNNNTYWCLRTVNETHNFLFCEFATGFLEYFDMNTDPYQLTNTVHTVERGILNQLHVQLMELRSCQGYKQCNPRPKNLDVGNKDGGSYDLHRGQLWDGWEG An isolated chimeric polypeptide encoding Z21368_PEA_1_P5, comprising: a sequence, wherein said first and second amino acid sequences are in contiguous and sequential order.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding the edge portion of Z21368_PEA_1_P5, having a length “n”, where n is at least about 10 amino acids long, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length, most preferably at least about 50 amino acids in length), wherein at least two amino acids comprise LA; A polypeptide having a sequence beginning with any of the numbers 57-x to 57 and ending with the amino acid number 58 + ((n-2) -x), wherein x varies from 0 to n-2. Provided is an isolated chimeric polypeptide encoding an edge portion of Z21368_PEA_1_P5, including:

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding Z21368_PEA_1_P15, corresponding to amino acids 1-416 of SUL1_HUMAN, corresponding to amino acids 1-416 of Z21368_PEA_1_P15 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSLQVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESINYFKMSKRMYPHRPVMMVISH APHGPEDSAPQFSKLYPNASQHITPSYNYAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNMLVETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEPGSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFLVERG and containing at least 90% homologous first amino acid sequence, provides an isolated chimeric polypeptide coding Z21368_PEA_1_P15.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding Z21368_PEA_1_P16, corresponding to amino acids 1-397 of SUL1_HUMAN, corresponding to amino acids 1-397 of Z21368_PEA_1_P16 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSLQVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESINYFKMSKRMYPHRPVMMVISH A first amino acid sequence at least 90% homologous to EipieichiJipiidiesueiPikyuefuesukeieruwaiPienueiesukyueichiaitiPiesuwaienuwaieiPienuemudikeieichidaburyuaiemukyuwaitiJipiemueruPiaieichiemuiefutienuaierukyuarukeiaruerukyutieruemuesubuididiesubuiiarueruwaienuemuerubuiitijiieruienutiwaiaiaiwaitieidieichijiwaieichiaijikyuefujierubuikeijikeiesuemuPiwaidiefudiaiarubuiPiefuefuaiaruJipiesubuiiPijiesuaibuiPikyuaibuieruenuaidierueiPitiaierudiaieiGLDTPPDVDGKSVLKLLDPEKPGNR, polypeptide at least 70% with a sequence corresponding to CVIVPPLSQPQIH to amino acid 398-410 of Z21368_PEA_1_P16, optionally at least 80%, preferably at least 85%, more Preferably a second at least 90%, most preferably at least 95% homologous. And a amino acid sequence, wherein the first and second amino acid distribution is contiguous, and in sequential order, provides an isolated chimeric polypeptide coding Z21368_PEA_1_P16.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of Z21368_PEA_1_P16, comprising at least 70%, optionally at least about 80%, preferably at least about 85% of the sequence CVIVPPLSQPQIH in Z21368_PEA_1_P16. More preferably, provided is an isolated polypeptide encoding the tail of Z21368_PEA_1_P16, comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide coding Z21368_PEA_1_P22, corresponding to amino acids 1-188 of SUL1_HUMAN, at least 90% homologous with the corresponding MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSLQVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAK to amino acids 1-188 of Z21368_PEA_1_P22 First amino acid sequence, Z21368_PEA A polypeptide having a sequence ARYDDGDQPRCAPRPRGSPTVF corresponding to amino acids 189-210 of 1_P22 at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous An isolated chimeric polypeptide encoding Z21368_PEA_1_P22, comprising two amino acid sequences, wherein said first and second amino acid sequences are in contiguous and sequential order.

  According to a preferred embodiment of the invention, an isolated polypeptide encoding the tail of Z21368_PEA_1_P22, comprising at least 70%, optionally at least about 80%, preferably at least about 85%, of the sequence ARYDGDQPRCAPRPRGLSPTVF in Z21368_PEA_1_P22 More preferably, provided is an isolated polypeptide encoding the tail of Z21368_PEA_1_P22, comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, the isolated chimeric polypeptide encoding Z21368_PEA_1_P23, which corresponds to amino acids 1 to 137 of Q7 Z2 W2 and also to amino acids 1 to 137 of Z21 368 PEA_1 _P23, corresponds to At least 70% optionally with a polypeptide having the first amino acid sequence and the sequence GLLHRLNH corresponding to amino acids 138-145 of Z21368_PEA_1_P23 Alternatively, it comprises a second amino acid sequence that is at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous, said first and second amino acid sequences being adjacent And provides an isolated chimeric polypeptide encoding Z21368_PEA_1_P23, in sequential order.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of Z21368_PEA_1_P23, which is at least 70%, optionally at least about 80%, preferably at least about 85%, with the sequence GLLHRLNH in Z21368_PEA_1_P23. More preferably, provided is an isolated polypeptide encoding the tail of Z21368_PEA_1_P23, comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, the isolated chimeric polypeptide encoding Z21368_PEA_1_P23, which corresponds to amino acids 1-137 of SUL1_HUMAN, and also corresponds to amino acids 1-137 of Z21368_PEA_1_P23, is MKYSCCALVLGLSLQIRQNQTLILDTLQHITH I I I I I G I A polypeptide having the first amino acid sequence and the sequence GLLHRLNH corresponding to amino acids 138 to 145 of Z21368_PEA_1_P23; A second amino acid sequence, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous, wherein said first and second amino acid sequences are Provided is an isolated chimeric polypeptide encoding Z21368_PEA_1_P23 adjacent and in sequential order.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of Z21368_PEA_1_P23, which is at least 70%, optionally at least about 80%, preferably at least about 85%, with the sequence GLLHRLNH in Z21368_PEA_1_P23. More preferably, provided is an isolated polypeptide encoding the tail of Z21368_PEA_1_P23, comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, the isolated chimeric polypeptide encoding HUMGRP5E_P4, corresponding to amino acids 1 to 127 of GRP_HUMAN and corresponding to amino acids 1 to 127 of HUMGRP5E_P4, also corresponds to The first amino acid sequence corresponds to amino acids 135 to 148 of GRP_HUMAN, and also corresponds to amino acids 128 to 141 of HUMGRP5E_P4, and is at least 90% homologous to GSQREGRNPQLNQQ And a amino acid sequence, wherein the first and second amino acid distribution is contiguous, and in sequential order, provides an isolated chimeric polypeptide coding HUMGRP5E_P4.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding the rim portion of HUMGRP5E_P4, comprising a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length, most preferably at least about 50 amino acids in length), wherein at least two amino acids comprise KG and have the following structure: A polypeptide having a sequence beginning with any of the numbers 127-x to 127 and ending with the amino acid number 128 + ((n-2) -x), wherein x varies from 0 to n-2. Provided is an isolated chimeric polypeptide encoding an edge portion of HUMGRP5E_P4, including:

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding HUMGRP5E_P5, corresponding to amino acids 1 to 127 of GRP_HUMAN and corresponding to amino acids 1 to 127 of HUMGRP5E_P5, also corresponding to At least 70%, optionally at least 80% preferably with a polypeptide having the first amino acid sequence and the sequence DSLLQVLNVKEGTPS corresponding to amino acids 128-142 of HUMGRP5E_P5 Or a second amino acid sequence which is at least 85%, more preferably at least 90%, most preferably at least 95% homologous, said first and second amino acid sequences being adjacent and in a consecutive order Provided is an isolated chimeric polypeptide encoding HUMGRP5E_P5.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of HUMGRP5E_P5, comprising at least 70%, optionally at least about 80%, preferably at least about 85%, of the sequence DSLLQVLNVKEGTPS in HUMGRP5E_P5. Provided is an isolated polypeptide encoding the tail of HUMGRP5E_P5, more preferably comprising a polypeptide that is at least about 90%, and most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding D56406_PEA_1_P2, which corresponds to amino acids 1-120 of NEUT_HUMAN and also corresponds to amino acids 1-120 of D56406_PEA_1_P2, is MMAGMKIQLVCMCLLAFSLSCSLSESLSCSLESCLSEEMSLTCSLECSHIGHGLITHITHI At least a polypeptide having the first amino acid sequence and the sequence ARWLTPVIPALWEAETGGSRGQEMETIPANT corresponding to amino acids 121 to 151 of D56406_PEA_1_P2 A second amino acid sequence of 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95%, corresponding to amino acids 121 to 170 of NEUT_HUMAN, D56406_PEA_1_P2 And a third amino acid sequence that is at least 90% homologous to LIQEDILDTGNDKNGKEEVIKRKIPYILKRQLYENKPRRPYILKRDSYYY, which also corresponds to amino acids 152-201 of SEQ ID NO: 1, wherein said first, second and third amino acid sequences are adjacent and in a consecutive order, Provided is an isolated chimeric polypeptide encoding D56406_PEA_1_P2.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the edge portion of D56406_PEA_1_P2, which is at least 70%, optionally at least about 80%, preferably at least 70% of the sequence encoding ARWLTPVIPALWEAETGGSRGQEMETIPANT corresponding to D56406_PEA_1_P2 Provided is an isolated polypeptide encoding an edge portion of D56406_PEA_1_P2 comprising an amino acid sequence that is at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, it is an isolated chimeric polypeptide encoding D56406_PEA_1_P5, which is at least 90% homologous to MMAGMKI QLVCMCLLAFSSWLC corresponding to amino acids 1-23 of NEUT_HUMAN and also corresponding to amino acids 1-23 of D56406_PEA_1_P5. SEEMEKALEADFLTTNMHTSKISKAHVPS WKMTLNVCSL VNLESPLEHPELEQLHHKICHSTRAFQHWELIQEDLITGIPGIKE corresponds to amino acid 26 to 170 of NEUT_HUMAN and also corresponds to amino acid 24 to 168 of DUT4406_PEA_1_P5. LKRQLYENKPRRPYILKRDSYYY and and at least 90% homologous to a second amino acid sequence, wherein the first and second amino acid distribution is contiguous, and in sequential order, provides an isolated chimeric polypeptide coding D56406_PEA_1_P5.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding the edge portion of D56406_PEA_1_P5, having a length “n”, wherein n is at least about 10 amino acids long, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length, most preferably at least about 50 amino acids in length), wherein at least two amino acids comprise CS and have the following structure: A polypeptide having a sequence beginning with any of the numbers 23-x-24 and ending with the amino acid number + ((n-2) -x), where x varies from 0 to n-2. Provided is an isolated chimeric polypeptide encoding an edge portion of D56406_PEA_1_P5, including:

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding D56406_PEA_1_P6, which corresponds to amino acids 1 to 45 of NEUT_HUMAN and also to amino acids 1 to 45 of D56406_PEA_1_P6 at least 90% homologous to MMAGMKIQL The first and second amino acid sequences, and LIQEDILTDGNDNGNGEKEVIKRKIK YPRK YLYKRQLYENKPRLYNKDSYYY corresponding to amino acids 121 to 170 of NEUT_HUMAN and also to amino acids 46 to 95 of D56406_PEA_1_P6, comprising the first and second amino acid sequences The amino acid sequences are adjacent and In connection with the order, it provides an isolated chimeric polypeptide coding D56406_PEA_1_P6.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding the edge portion of D56406_PEA_1_P6, having a length “n”, wherein n is at least about 10 amino acids long, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length, most preferably at least about 50 amino acids in length), wherein at least two amino acids comprise KL and have the following structure: A polypeptide having a sequence beginning with any of the numbers 45-x to 46 and ending with the amino acid number 46 + ((n-2) -x), wherein x varies from 0 to n-2. Provided is an isolated chimeric polypeptide encoding an edge portion of D56406_PEA_1_P6, including:

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding F05068_PEA_1_P7, which corresponds to amino acids 1 to 33 of ADML_HUMAN and also corresponds to amino acids 1 to 33 of F05068_PEA_1_P7 at least 90% homologous to MKLVS Provided is an isolated chimeric polypeptide encoding F05068_PEA_1_P7, comprising a first amino acid sequence.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding F05068_PEA_1_P8, which corresponds to amino acids 1 to 82 of ADML_HUMAN and also to amino acids 1 to 82 of F05068_PEA_1_P8. At least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably a polypeptide having a first amino acid sequence and a sequence R corresponding to amino acids 83 to 83 of F05068_PEA_1_P8 Is at least 95% homologous to the second And a acid sequence, wherein the first and second amino acid distribution is contiguous, and in sequential order, provides an isolated chimeric polypeptide coding F05068_PEA_1_P8.

  According to a preferred embodiment of the present invention, the isolated chimeric polypeptide encoding H14624_J15 is an H15624_P15 encoding, corresponding to amino acids 1 to 167 of Q9 HAP5, and also corresponding to amino acids 1 to 167 of H14624_P15. A amino acid sequence having a first amino acid sequence and a sequence GKPSLLLPHSLLG corresponding to amino acids 168 to 180 of H14624_P15 Said first and second comprising a peptide and a second amino acid sequence which is at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous. The present invention provides an isolated chimeric polypeptide encoding H14624_P15, wherein the amino acid sequences of SEQ ID NO: are in contiguous and sequential order.

  According to a preferred embodiment of the invention, an isolated polypeptide encoding the tail of H14624_P15, comprising at least 70%, optionally at least about 80%, preferably at least about 85% of the sequence GKPSLLLLPHSLLG in H14624_P15. Provided is an isolated polypeptide encoding the tail of H14624_P15, more preferably comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding H38804_PEA_1_P5, comprising at least 70%, optionally at least 80% of a polypeptide having the sequence MGRVRTLAGECSAAQAQLALAVSVLSAPPSGTPSALDPWSGLWAPVLQ corresponding to amino acids 1 to 57 of H38804_PEA_1_P5 MTGSNEFKLNQPPEDGISSVKFSPNTSQFLLVSSWSTS, corresponding to a first amino acid sequence, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous and corresponding to amino acids 1-324 of BUB3_HUMAN and also to amino acids 58-381 of H38804_PEA_1_P5 YDVPANSMRLKYQHTGAVLDCAFYDPTHAWSGGLDHQLKMHDLNTDQENLVGTHDAPIRCVEYCPEVNVMVTGSWDQTVKLWDPRTPCNAGTFSQPEKVYTLSVSGDRLIVGTAGRRVLVWDLRNMGYVQQRRESSLKYQTRCIRAFPNKQGYVLSSIEGRVAVEYLDPSPEVQKKKYAFKCHRLKENNIEQIYPVNAISFHNIHNTFATGGSDGFVNIWDPFNKKRLCQFHRYPTSIASLAFSNDGTTLAIASSYMYEMDDTEHPEDGIFIRQVTDAETKPK and and at least 90% homologous to a second amino acid sequence, wherein the first and second amino acid distribution is contiguous, and In connection with the order, it provides an isolated chimeric polypeptide coding H38804_PEA_1_P5.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tip of H38804_PEA_1_P5, which is at least 70%, optionally at least about 80%, preferably at least about 85%, of the sequence MGRVRTLAGECSAAQAQLASLVLSAPPS SGGTPSALDPWSGLWAPVLQ of H38804_PEA_1_P5 Provided is an isolated polypeptide encoding the tip of H38804_PEA_1_P5, which preferably comprises a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding H38804_PEA_1_P17, comprising at least 70%, optionally at least 80% of a polypeptide having the sequence MGRVRTLAGECSAAQAQLASLVLSAPPSGTPSALDPWSGLWAPVLQ corresponding to amino acids 1 to 57 of H38804_PEA_1_P17 , Preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous to the first amino acid sequence corresponding to amino acids 1-328 of BUB3_HUMAN and also corresponding to amino acids 58-385 of H38804_PEA_1_P17 VRLYDVPANSMRLKYQHTGAVLDCAFYDPTHAWSGGLDHQLKMHDLNTDQENLVGTHDAPIRCVEYCPEVNVMVTGSWDQTVKLWDPRTPCNAGTFSQPEKVYTLSVSGDRLIVGTAGRRVLVWDLRNMGYVQQRRESSLKYQTRCIRAFPNKQGYVLSSIEGRVAVEYLDPSPEVQKKKYAFKCHRLKENNIEQIYPVNAISFHNIHNTFATGGSDGFVNIWDPFNKKRLCQFHRYPTSIASLAFSNDGTTLAIASSYMYEMDDTEHPEDGIFIRQVTDAETKPKSPCT and and at least 90% homologous to a second amino acid sequence, wherein the first and second amino acid distribution is Adjacent, and in sequential order, it provides an isolated chimeric polypeptide coding H38804_PEA_1_P17.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tip of H38804_PEA_1_P17, which is at least 70%, optionally at least about 80%, preferably at least about 85%, of the sequence MGRVRTLAGECSAAQAQALSA Provided is an isolated polypeptide encoding the tip of H38804_PEA_1_P17, which comprises a polypeptide that is preferably at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding HSENA 78_P2, corresponding to amino acids 1 to 81 of SZ05_HUMAN and corresponding to amino acids 1 to 81 of HSENA 78_P2, MSLL SSRA Provided is an isolated chimeric polypeptide encoding HSENA 78_P2 comprising a first amino acid sequence.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding HUMODCA_P9 comprising at least 70%, optionally at least 80% of the polypeptide having the sequence MKSLTATSSMKVLLPRTFWTRKLMKFLLL corresponding to amino acids 1-29 of HUMODCA_P9 LVLRIA TDD SKAVCRL SV KFAGLT RIDEL VEG HV GS GC TD PET F F V Q AIS DALG M DIGGGFPGSEDVKLKFEEITGVINPALDKYFPSDSGVRIIAEPGRYYVASAFTLAVNIIAKKIVLKEQTGSDDEDESSEQTFMYYVNDGVYGSFNCILYDHAHVKPLLQKRPKPDEKYYSSSIWGPTCDGLDRIVERCDLPEMHVGDWMLFENMGAYTVAAASTFNGFQRPTIYYVMSGPAWQLMQQFQNPDFPPEVEEQDASTLPVSCAWESGMKRHRAACASASINV and and at least 90% homologous to a second amino acid sequence, wherein the first and second amino acid distribution is contiguous, and in sequential order, provides an isolated chimeric polypeptide coding HUMODCA_P9 .

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tip of HUMODCA_P9, comprising at least 70%, optionally at least about 80%, preferably at least about 85%, of the sequence MKSLTATSSMKVLLPRTF WTRKLMKFLLL of HUMODCA_P9 Provided is an isolated polypeptide encoding the tip of HUMODCA_P9 comprising a polypeptide that is preferably at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding HUMODCA_P9 comprising at least 70%, optionally at least 80% of the polypeptide having the sequence MKSLTATSSMKVLLPRTFWTRKLMKFLLL corresponding to amino acids 1-29 of HUMODCA_P9 LVLRIA TDD SKAVCRL SV KF GATRL T ID VVG SF HGF GS GC TD PET F V Q AIS DALS DAV G GGFPGSEDVKLKFEEITGVINPALDKYFPSDSGVRIIAEPGRYYVASAFTLAVNIIAKKIVLKEQTGSDDEDESSEQTFMYYVNDGVYGSFNCILYDHAHVKPLLQKRPKPDEKYYSSSIWGPTCDGLDRIVERCDLPEMHVGDWMLFENMGAYTVAAASTFNGFQRPTIYYVMSGPAWQLMQQFQNPDFPPEVEEQDASTLPVSCAWESGMKRHRAACASASINV and and at least 90% homologous to a second amino acid sequence, wherein the first and second amino acid distribution is contiguous, and in sequential order, provides an isolated chimeric polypeptide coding HUMODCA_P9 .

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tip of HUMODCA_P9, comprising at least 70%, optionally at least about 80%, preferably at least about 85%, of the sequence MKSLTATSSMKVLLPRTF WTRKLMKFLLL of HUMODCA_P9 Provided is an isolated polypeptide encoding the tip of HUMODCA_P9 comprising a polypeptide that is preferably at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding HUMODCA_P9 comprising at least 70%, optionally at least 80% of the polypeptide having the sequence MKSLTATSSMKVLLPRTFWTRKLMKFLLL corresponding to amino acids 1-29 of HUMODCA_P9 LVLRIA TDD SKAVCRL SV KFAGLT RIV EL KELIGNID V VG V SF G GS G PET F F V Q AIS DALS L GGFPGSEDVKLKFEEITGVINPALDKYFPSDSGVRIIAEPGRYYVASAFTLAVNIIAKKIVLKEQTGSDDEDESSEQTFMYYVNDGVYGSFNCILYDHAHVKPLLQKRPKPDEKYYSSSIWGPTCDGLDRIVERCDLPEMHVGDWMLFENMGAYTVAAASTFNGFQRPTIYYVMSGPAWQLMQQFQNPDFPPEVEEQDASTLPVSCAWESGMKRHRAACASASINV and and at least 90% homologous to a second amino acid sequence, wherein the first and second amino acid distribution is contiguous, and in sequential order, provides an isolated chimeric polypeptide coding HUMODCA_P9 .

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tip of HUMODCA_P9, comprising at least 70%, optionally at least about 80%, preferably at least about 85%, of the sequence MKSLTATSSMKVLLPRTF WTRKLMKFLLL of HUMODCA_P9 Provided is an isolated polypeptide encoding the tip of HUMODCA_P9 comprising a polypeptide that is preferably at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding R00299_P3 comprising at least 70%, optionally at least 80% of the polypeptide having the sequence MAEKALLCPSSAGLGTWPWVLNSAWPVLPLAVDQGVDWRPRGPV corresponding to amino acids 1-44 of R00299_P3 , Preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous to the first amino acid sequence and corresponding to amino acids 74 to 191 of Q9NWT9 and also to amino acids 45 to 162 of R00299_P3 An isolated chimeric polypeptide encoding R00299_P3 comprising a second amino acid sequence at least 90% homologous to RPIDTTM DEEQVELSRKEKLRFLFHMYDSDSDGRITLEYYRNV, said first, second and third amino acid sequences being adjacent and in sequential order I will provide a.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tip of R00299_P3 comprising at least 70%, optionally at least about 80%, preferably at least about 85%, of the sequence MAEKALLCPSSAGLGTWPWVLNSAWPVLPLDVGVDWRPRGPV of the sequence R00299_P3 Provided is an isolated polypeptide encoding the tip of R00299_P3 comprising a polypeptide that is preferably at least about 90%, and most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of R00299_P3, which is at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85% More preferably, an isolated polypeptide encoding the tail of R00299_P3 comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding R00299_P3 comprising at least 70%, optionally at least 80% of the polypeptide having the sequence MAEKALLCPSSAGLGTWPWVLNSAWPVLPLAVDQGVDWRPRGPV corresponding to amino acids 1-44 of R00299_P3 Preferably, at least 85%, more preferably at least 90%, most preferably at least 95% homologous to the first amino acid sequence corresponding to amino acids 21 to 214 of TESC_HUMAN and also corresponding to amino acids 45 to 238 of R00299_P3 MSYFRPIDTTMDEEQVELSRKEKLRFLFHMYDSDSDGRITLEEYRNVVEELLSGNPHIEKESARSIADGAMMEAASVCMGQMEPDQVYEGITFEDFLKIWQGIDIETKMHVRFLNMETMALCH and and at least 90% homologous to a second amino acid sequence, wherein the first and second amino acid distribution is contiguous, and in sequential order, provides an isolated chimeric polypeptide coding R00299_P3.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tip of R00299_P3 comprising at least 70%, optionally at least about 80%, preferably at least about 85%, of the sequence MAEKALLCPSSAGLGTWPWVLNSAWPVLPLDVGVDWRPRGPV of the sequence R00299_P3 Provided is an isolated polypeptide encoding the tip of R00299_P3 comprising a polypeptide that is preferably at least about 90%, and most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, it is an isolated chimeric polypeptide encoding W60282_PEA_1_P14, which corresponds to amino acids 1 to 66 of Q8IXD7 and also to amino acids 1 to 66 of W60282_PEA_1_P14. The polypeptide having the first amino acid sequence and the sequence TPASHLAMRQHHHH corresponding to amino acids 67-80 of W60282_PEA_1_P14 and at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably Is a second amino acid sequence that is at least 95% homologous Wherein the door, the first and second amino acid distribution is contiguous, and in sequential order, provides an isolated chimeric polypeptide coding W60282_PEA_1_P14.

  According to a preferred embodiment of the invention, an isolated polypeptide encoding the tail of W60282_PEA_1_P14, comprising at least 70%, optionally at least about 80%, preferably at least about 85% of the sequence TPASHLAMQHHHH in W60282_PEA_1_P14 More preferably, provided is an isolated polypeptide encoding the tail of W60282_PEA_1_P14, comprising a polypeptide that is at least about 90%, and most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding Z41644_PEA_1_P10, corresponding to amino acids 1-95 of SZ14_HUMAN and also corresponding to amino acids 1-95 of Z41644_PEA_1_P10 The polypeptide having the first amino acid sequence and the sequence YAPPLLTFLPTRPSCGGSQDGKGPPHQVI corresponding to amino acids 96 to 123 of Z41644_PEA_1_P10 at least 70%, optionally at least 80%, preferably less Z41644_PEA_1_P10 also comprising a second amino acid sequence which is also 85%, more preferably at least 90%, most preferably at least 95% homologous, said first and second amino acid sequences being adjacent and in sequential order An isolated chimeric polypeptide encoding

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of Z41644_PEA_1_P10, which is at least 70%, optionally at least about 80%, preferably at least about 85%, with the sequence YAPPLLTFLPTRPSCSGSQDGKGPPHQVI in Z41644_PEA_1_P10 More preferably, provided is an isolated polypeptide encoding the tail of Z41644_PEA_1_P10, comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding Z41644_PEA_1_P10, corresponding to amino acids 13 to 107 of Q9 NS21 and also corresponding to amino acids 1 to 95 of Z41644 _PEA_1_P10. At least 70%, optionally at least 80%, preferably at least 80%, preferably at least 80%, of the polypeptide having the first amino acid sequence and the sequence YAPPLLTFLPTRPSCGGSQDGKGPPHQVI corresponding to amino acids 96 to 123 of Z41644_PEA_1_P10 Z41644_PEA_1_P10 comprising a second amino acid sequence that is 5%, more preferably at least 90%, most preferably at least 95% homologous, said first and second amino acid sequences being in a contiguous and consecutive order Provided is an isolated chimeric polypeptide that encodes.

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of Z41644_PEA_1_P10, which is at least 70%, optionally at least about 80%, preferably at least about 85%, with the sequence YAPPLLTFLPTRPSCSGSQDGKGPPHQVI in Z41644_PEA_1_P10 More preferably, provided is an isolated polypeptide encoding the tail of Z41644_PEA_1_P10, comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, an isolated chimeric polypeptide encoding Z41644_PEA_1_P10, corresponding to amino acids 13 to 107 of AAQ 89 265 and also corresponding to amino acids 1 to 95 of Z41644_PEA_1_P10 MRL The polypeptide having the first amino acid sequence and the sequence YAPPLLTFLPTRPSCGGSQDGKGPPHQVI corresponding to amino acids 96 to 123 of Z41644_PEA_1_P10 at least 70%, optionally at least 80%, preferably less Z41644_PEA_1_P10 also comprising a second amino acid sequence which is also 85%, more preferably at least 90%, most preferably at least 95% homologous, said first and second amino acid sequences being adjacent and in sequential order An isolated chimeric polypeptide encoding

  According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of Z41644_PEA_1_P10, which is at least 70%, optionally at least about 80%, preferably at least about 85%, with the sequence YAPPLLTFLPTRPSCSGSQDGKGPPHQVI in Z41644_PEA_1_P10 More preferably, provided is an isolated polypeptide encoding the tail of Z41644_PEA_1_P10, comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  According to a preferred embodiment of the present invention, there is provided an antibody capable of specifically binding to an epitope of an amino acid sequence.

  Optionally, the amino acid sequence corresponds to a bridge, an edge, a tail, a tip, or an insertion.

  Optionally, the antibody can distinguish between splice variants carrying said epitope and the corresponding known proteins.

  According to a preferred embodiment of the present invention, there is provided a kit for detecting a lung cancer which detects overexpression of the splice variant according to any one of the above claims.

  Optionally, the kit comprises NAT based technology.

  Optionally, the kit further comprises at least one primer pair capable of selectively hybridizing to the nucleic acid sequence according to any one of the preceding claims.

  Optionally, the kit further comprises at least one oligonucleotide capable of selectively hybridizing to the nucleic acid sequence according to any one of the preceding claims.

  Optionally, the kit comprises an antibody according to any one of the preceding claims.

  Optionally, the kit further comprises at least one reagent for performing an ELISA or Western blot.

  According to a preferred embodiment of the present invention, a method of detecting lung cancer comprising the step of detecting overexpression of the splice variant according to any one of the preceding claims.

  Optionally, detection of overexpression is performed using NAT based technology.

  Optionally, detection of overexpression is performed using an immunoassay.

  Optionally, the immunoassay comprises an antibody according to any one of the preceding claims.

  According to a preferred embodiment of the present invention there is provided a biomarker capable of detecting lung cancer comprising any of the above nucleic acid sequences or fragments thereof or the above amino acid sequences or fragments thereof.

  According to a preferred embodiment of the present invention, there is provided a method of screening for lung cancer, comprising the step of detecting lung cancer cells with the biomarker or method or assay according to any one of the above claims.

  According to a preferred embodiment of the present invention, there is provided a method of diagnosing a lung cancer, comprising the step of detecting lung cancer cells with the biomarker or antibody or method or assay according to any one of the preceding claims.

  According to a preferred embodiment of the present invention, the disease progression and / or the therapeutic efficacy and / or the step of detecting lung cancer cells with a biomarker or antibody or method or assay according to any one of the preceding claims. Or provide a method to monitor the recurrence of lung cancer.

  According to a preferred embodiment of the present invention, the method comprises detecting lung cancer cells with the biomarker or antibody or method or assay according to any one of the preceding claims, and selecting a treatment by said detection. Provide a method of choice for lung cancer treatment.

  Unless defined otherwise, all technical and scientific terms used herein have meanings as commonly understood by one of ordinary skill in the art to which this invention belongs. The following references give the person skilled in the art a general definition of the many terms used in the present invention: Singleton et al. Dictionary of Microbiology and Molecular Biology (2nd ed. 1994); The Cambridge Dictionary of Science and Technology (Walker ed., 1988); The Glossary of Genetics, 5th Ed. , R. Rieger et al. (Eds.), Springer Verlag (1991); and Hale & Marham, The Harper Collins Dictionary of Biology (1991). All of which are incorporated herein by reference as if fully set forth herein. As used herein, the following terms have the meaning ascribed to them, unless otherwise specified.

DESCRIPTION OF PREFERRED EMBODIMENTS The present invention is a novel sensitive and accurate novel lung cancer marker. Furthermore, at least certain of these markers, alone or in combination, can distinguish different types of lung cancer, such as small cell carcinoma, large cell carcinoma, squamous cell carcinoma, and adenocarcinoma. These markers are differentially expressed, preferably overexpressed, in lung cancer, in contrast to normal lung tissue. Measurement of these markers alone or in combination in patient samples provides information that can be correlated with a promising lung cancer diagnosis by a diagnostician. The marker of the present invention is highly differentially detected between lung cancer and non-cancerous condition alone or in combination. The markers of the present invention can be used alone or in combination for prognosis, prediction, screening, early screening, treatment selection, treatment monitoring of lung cancer. For example, optionally and preferably, these markers can be used for staging of lung cancer and / or monitoring of disease progression. In addition, the markers of the present invention can be used alone or in combination to detect metastatic sources found at anatomical locations other than lung. Also, one or more markers can optionally be used in combination with one or more other cancer markers (other than those described herein). According to optional embodiments of the invention, such combinations can be used to distinguish different types of lung cancer, such as small cell carcinoma, large cell carcinoma, squamous cell carcinoma, and adenocarcinoma. In addition, the markers of the invention, alone or in combination, can be used for detection of other tumor types by elimination (eg detection of carcinoid tumors accounting for 5% of lung cancers).

  The markers of the present invention can be used alone or in combination for lung cancer prognosis, prognosis, screening, early screening, staging, selection of treatment, monitoring of treatment. For example, optionally and preferably, these markers can be used for staging of lung cancer and / or monitoring of disease progression. In addition, the markers of the present invention can be used alone or in combination to detect metastatic sources found at anatomical locations other than lung. Also, one or more markers can optionally be used in combination with one or more other cancer markers (other than those described herein).

  The biomolecular sequences (amino acid sequences and / or nucleic acid sequences) which are revealed using the method of the invention and described herein as a tissue or pathological marker for the treatment or prevention of a disease and / or Or it can be effectively used as a drug or drug target.

  These markers are specifically released into the bloodstream under lung cancer conditions and / or are otherwise expressed or specifically expressed at higher levels in lung cancer tissues or cells. Measurement of these markers alone or in combination in patient samples provides information that can be correlated with a promising lung cancer diagnosis by a diagnostician.

  Thus, the present invention also provides a diagnostic assay for lung cancer and / or indicative condition, and optionally and preferably, lung cancer in a sample taken from a subject (patient), more preferably in some blood sample types and / or Or to the use of such markers for the detection of an indicative condition.

  In another embodiment, the invention relates to crosslinks, tails, tips and / or insertions, and / or analogues, homologues and derivatives of such peptides. Such crosslinking, tails, tips and / or insertions are described in more detail in the examples.

  As used herein, "tail" refers to the peptide sequence at the end of the amino acid sequence unique to the splice variant of the invention. Thus, optionally, such tailed splice variants are typically highly homologous to the part of the known protein to which at least a first part of the splice variant corresponds (frequently 100% identical) And at least a second part of the variant may be considered as a chimera in that it comprises a tail.

  As used herein, "tip" refers to the first peptide sequence of an amino acid sequence unique to a splice variant of the invention. Thus, a splice variant having such a tip, optionally, wherein at least a first portion of the splice variant comprises a tip and at least a second portion is typically a portion of the corresponding known protein It can be regarded as a chimera in that it is highly homologous (often 100% identical).

  As used herein, "edge portion" refers to a connection between two parts of a splice variant of the invention that has not been linked in wild-type or known proteins. The rim may optionally be caused by the linkage between the above-mentioned "known protein" portion of the variant and the tail and / or, for example, when the internal part of the wild-type sequence is no longer present The two parts of the sequence that were not previously adjacent in the known protein are adjacent in the splice variant. The "cross-linking" may optionally be the above mentioned edge, but at the junction between the tip and the variant "known protein" moiety, the tail and the variant "known protein" moiety Or between the insertion and the variant "known protein" may also be included.

  Optionally and preferably, the cross-linking between the tail, the tip, or the unique insertion and the variant "known protein" moiety is at least about 10 amino acids, more preferably at least about 20 amino acids, more preferably at least about Thirty amino acids, even more preferably at least about 40 amino acids, of which at least one amino acid is derived from tail / tip / insertion and at least one amino acid is derived from the variant "known protein" portion. Also, optionally, the crosslinks are any number from about 10 to about 40 (e.g. 10, 11, 12, 13, ... 37, 38, 39, 40 amino acids long or any number in between) May contain amino acids of

  It should be noted that the crosslinks can not extend beyond the length of the sequence in either direction, and for each description of the crosslink, in such a way that the length of the crosslink does not extend beyond the sequence itself It should be assumed that it is read.

  In addition, we will describe bridging in terms of sliding windows in the following fixed contexts: For example, certain descriptions of crosslinking are characterized as follows: Optionally, the crosslinking between the two edges (some of the known proteins are not present in the variant) is described as follows: Capable: Cross-linked moiety of CONTIG-NAME_P1 (indicating the protein name) (length “n” (wherein n is at least about 10 amino acids long, optionally at least about 20 amino acids long, preferably at least about 30 amino acids long) , More preferably at least about 40 amino acids in length, most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise XX (two amino acids at the center of the bridge, from each end of the rim), The following structure (numbering according to the sequence of CONTIG-NAME_P1): starting from any of amino acids 49-x to 49 (for example), amino acids No. 50 + ((n-2) -x) (for example) (wherein x varies from 0 to n-2), and includes a polypeptide. It should be read to include a cross-link that is any amino acid number between 50 amino acids long Further, the cross-linked polypeptide can not extend beyond the sequence, and thus 49-x (for example) is at least 1. Yes, 50 + ((n-2) -x) (for example) should be read so as not to exceed the total amino acid length.

  In another embodiment, the invention provides antibodies that specifically recognize the splice variants of the invention and peptide fragments thereof. Preferably, such an antibody differentially recognizes the splice variants of the present invention, but the corresponding known proteins (such known proteins are discussed in relation to the splice variants in the following examples) not recognize.

  In another embodiment, the present invention is an isolated nucleic acid molecule encoding a splice variant of the invention and having the nucleotide sequence set forth in any one of the sequences listed herein or a sequence complementary thereto. I will provide a. In another embodiment, the invention provides an isolated nucleic acid molecule having a nucleotide sequence set forth in any one of the sequences listed herein, or a sequence complementary thereto. In another embodiment, the invention provides an oligonucleotide of at least about 12 nucleotides capable of specifically hybridizing to a nucleic acid molecule of the invention. In another embodiment, the invention provides vectors, cells, liposomes, and compositions comprising the isolated nucleic acids of the invention.

  In another embodiment, the present invention specifically refers to a known corresponding protein, wherein the antibody specifically interacts with a splice variant in a biological sample (the known protein is discussed with respect to the splice variant in the following examples) Contacting the biological sample with an antibody that specifically recognizes the splice variant of the present invention under conditions not recognizing A), detecting the interaction, and the presence of the interaction the presence of the splice variant in the biological sample And detecting and / or correlating the splice variant of the present invention in a biological sample.

  In another embodiment, the invention comprises the steps of hybridizing an isolated nucleic acid molecule or an oligonucleotide fragment of at least about the shortest length with nucleic acid material of a biological sample, detecting a hybridization complex, and hybridization. Provided is a method of detecting a nucleic acid sequence of a splice variant in a biological sample, including the presence of the complex correlating with the presence of the nucleic acid sequence of the splice variant in the biological sample.

  According to the invention, the splice variants described herein are examples of non-limiting markers for lung cancer diagnosis. Each splice variant marker of the present invention may be used alone or in combination in various applications (including but not limited to lung cancer prognosis, prognosis, screening, early screening, assessment of progression, treatment selection, and treatment monitoring) Can be used).

  According to an optional but preferred embodiment of the present invention, any of the markers of the present invention may optionally be used alone or in combination. Such combinations optionally include a plurality of markers described herein (optionally, any subcombination of markers and / or at least one other marker (eg, known) (Including a combination featuring a marker). Furthermore, such combinations are optionally and preferably any marker described herein and any other marker described herein, and / or any other known marker, It can be used as described above for the determination of the ratio of quantitative or semi-quantitative measurement between and / or any other marker. With regard to such a ratio between any marker (or combination thereof) described herein and the known marker, more preferably, the known marker is described in more detail below for each cluster or gene. "Known proteins" is included.

  According to another preferred embodiment of the invention, the nucleic acid sequence of the splice variant protein or fragment thereof or splice variant thereof or a fragment thereof can be characterized as a biomarker for lung cancer detection, whereby the biomarker is any Optionally, any of the above mentioned biomarkers can be included.

  According to yet another preferred embodiment of the present invention, optionally and preferably any amino acid sequence encoded by the nucleic acid sequence corresponding to the splice variant protein as described herein or a fragment thereof including. Any oligopeptides or peptides relating to such amino acid sequences or fragments thereof are optionally (additionally or alternatively) biomarkers (specific to those proteins expressed as tails, tips, insertions, edges or crosslinks It can also be used as an amino acid sequence, including but not limited to). The invention also optionally includes antibodies capable of recognizing and / or eliciting such oligonucleotides or proteins.

  The invention also optionally and preferably comprises any nucleic acid sequence or fragment or amino acid sequence or fragment thereof corresponding to the above-described splice variant of the invention for any application.

  Non-limiting examples of methods or assays are described below.

  The invention also relates to a kit based on such a diagnostic method or assay.

Nucleic Acid Sequences and Oligonucleotides Various embodiments of the invention encode similar polypeptides having the nucleic acid sequences described above, their sequence fragments, sequences hybridizable therewith, sequences homologous thereto, different codon usage Sequences, including altered sequences characterized by mutations such as deletions, insertions or substitutions of one or more naturally occurring or artificially derived nucleotides in a random or targeted manner.

  The present invention provides nucleic acid sequences as described herein, fragments thereof, sequences hybridizable therewith, sequences homologous thereto (eg at least 50%, at least 55%, at least 60% of the nucleic acid sequences described below) At least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 95%, or 100% identical), sequences encoding similar polypeptides with different codon usage, random or targeted And altered sequences characterized by mutations such as deletions, insertions, or substitutions of one or more naturally occurring or artificially derived nucleotides in a uniform manner. The invention also includes homologous nucleic acid sequences (ie, forming part of the polynucleotide sequences of the invention) comprising sequence regions unique to the polypeptides of the invention.

  Where the polynucleotide sequences of the invention encode a polypeptide that has not yet been identified, the invention also includes the novel polypeptides encoded by the isolated polynucleotides described above and their respective nucleic acid fragments or parts thereof .

  "Nucleic acid fragment", "oligonucleotide", or "polynucleotide" are used interchangeably herein to refer to a polymer of nucleic acid. The polynucleotide sequences of the present invention may be single-stranded isolated and provided in the form of RNA sequences, complementary polynucleotide sequences (cDNA), genomic polynucleotide sequences, and / or complex polynucleotide sequences (eg, combinations of the above). Or double-stranded nucleic acid sequence.

  As used herein, the phrase "complementary polynucleotide sequence" refers to a sequence from reverse transcription of messenger RNA using reverse transcriptase or any other RNA dependent DNA polymerase. Such sequences can then be amplified in vivo or in vitro using a DNA-dependent DNA polymerase.

  As used herein, the phrase "genomic polynucleotide sequence" refers to a sequence that is derived (isolated) from a chromosome, thereby indicating the flanking portion of the chromosome.

  As used herein, the phrase "composite polynucleotide sequence" refers to a sequence composed of genomic and cDNA sequences. The composite sequence may include some exon sequences necessary to encode the polypeptide of the present invention and some intron sequences intervening therebetween. Intron sequences can be derived from any source, including other genes, and typically include conserved splicing signal sequences. Such intron sequences may further include cis-acting expression regulatory elements.

  Preferred embodiments of the invention include oligonucleotide probes.

  An example of an oligonucleotide probe that can be utilized according to the invention is a sequence complementary to the unique sequence region of any variant of the invention (the amino acid sequence of the crosslink, tail, tip and / or insertion of the invention) A nucleotide sequence that encodes, and / or an equivalent portion of any of the nucleotide sequences described herein (including, but not limited to, the nucleotide sequences of nodes, segments, or amplicons described herein A single stranded polynucleotide, including, but not limited to).

  Alternatively, the oligonucleotide probe of the present invention may be a nucleic acid sequence included in any of the above nucleic acid sequences, in particular, a nucleotide sequence encoding the amino acid sequence of the crosslink, tail, tip and / or insertion of the portion (the present invention; And / or equivalent parts of any of the nucleotide sequences described herein, including but not limited to the node, segment, or amplicon nucleotide sequences described herein Can be designed to hybridize with (not limited to) these.

  Oligonucleotides designed by the techniques of the present invention can be generated according to any oligonucleotide synthesis method known in the art, such as enzyme synthesis or solid phase synthesis. Devices and reagents for performing solid phase synthesis are commercially available from, for example, Applied Biosystems. Any other such synthetic means can also be used, and the actual oligonucleotide synthesis is well within the ability of one skilled in the art, eg, solid phase chemistry (eg cyanoethyl phosphoramidite and subsequent) Deprotection, desalting, and purification using, for example, the automated Trityl-on (trityl-on) method or HPLC), "Molecular Cloning: A laboratory Manual" Sambrook et al. (1989); "Current Protocols in Molecular Biology" Volumes I-III Ausubel, R., et al. M. , Ed. (1994); Ausubel et al. , "Current Protocols in Molecular Biology", John Wiley and Sons, Baltimore, Maryland (1989); Perbal, "A Practical Guide to Molecular Cloning", John Wiley & Sons, New York (1988) and "Oligonucleotide Synthesis" Gait, M. . J. , Ed. It can be implemented by the established method detailed in (1984).

  Oligonucleotides used in accordance with this aspect of the invention may have from about 10 to about 200 bases, preferably about 15 to about 150 bases, more preferably about 20 to about 100 bases, most preferably about 20 to about 50 bases. It has a length selected from the range. Preferably, in the oligonucleotide of the present invention, at least 17 bases, at least 18 bases, at least 19 bases, at least 20 bases, at least 20 bases, at least 22 bases, at least 25 bases, at least 30 bases, or at least 40 bases are specific to the biomarkers of the present invention It is characterized in that it is hybridizable.

  The oligonucleotide of the present invention may comprise a heterocyclic nucleoside consisting of a purine and a pyrimidine base linked by a 3 'to 5' phosphodiester bond.

  Preferably, the oligonucleotides used are those modified with one or more backbones, internucleoside linkages, or bases, as broadly described below.

  Specific examples of preferred oligonucleotides useful in this aspect of the invention include oligonucleotides containing modified backbones or non-naturally occurring internucleoside linkages. Oligonucleotides having a modified backbone include, for example, U.S. Patent Nos. 4,469,863; 4,476,301; 5,023,243; 5,177,196; 188, 897; 5,264, 423; 5, 276, 019; 5, 278, 302; 5, 286, 717; 5, 321, 131; Nos. 5,399,676; 5,405,939; 5,453,496; 5,455,233; 5,466,677; 5,476. 5,925,126; 5,536,821; 5,541,306; 5,550,111; 5,563,253; 5,571,799; 5,587,361; and 5,625, As disclosed in No. 50, include those that retain a phosphorus atom in the backbone.

  Preferred modified oligonucleotide backbones include, for example, phosphorothioates, chiral phosphorothioates, phosphorodithioates, phosphotriesters, aluminum alkyl phosphotriesters, methyl and other alkyl phosphonates (including 3'-alkylene phosphonates and chiral phosphonates), Phosphinates, phosphoramidates (including 3'-aminophosphoramidates and aminoalkylphosphoramidates), thionophosphoramidates, thionoalkyl phosphonates, thionoalkyl phosphotriesters, and conventional 3'-5 ' Bonded boranophosphates, their 2'-5 'linked analogues, and adjacent pairs of nucleoside units are linked by 3'-5' and 5'-3 'or 2'-5' and 5'-2 ' The polarity is reversed It includes those. Various salts, mixed salts, and free acid forms can also be used.

Alternatively, the modified oligonucleotide backbone that does not contain a phosphorus atom can be a short alkyl or cycloalkyl internucleoside linkage, a mixed heteroatom and an alkyl or cycloalkyl internucleoside linkage, or one or more short heteroatoms or heterocyclic nucleosides. It has a skeleton formed by interlinking. These include morpholino linkages (part of which are formed from the sugar moieties of the nucleosides); siloxane backbone, sulfide, sulfoxide, and sulfone backbones; formacetyl and thioformacetyl backbones; methyleneformacetyl and thioformacetyl backbones; Alkene-containing backbone; sulfamate backbone; methyleneimino and methylenehydrazino backbone; sulfonate and sulfonamide backbone; backbone with amide backbone, and backbone with mixed N, O, S, and CH ₂ components, which include U.S. Patent Nos. 5,034,506; 5,166,315; 5,185,444; 5,214,134; 5,216,141; , 235, 033; the same 5,264, 562; the same 5,264, 5 No.64; No.5,405,938; No.5,434,257; No.5,466,677; No.5,470,967; No.5,489,677; 5,541,307; 5,561,225; 5,596,086; 5,602,240; 5,610,289; 5,602,240 No. 5,608,046; No. 5,610,289; No. 5,618,704; No. 5,623,070; No. 5,663,312; 633,360; 5,67,437; and 5,677,439.

  Other oligonucleotides that can be used in the present invention are those in which both the sugar and the internucleoside linkage have been modified (ie, the backbone of the nucleotide unit has been replaced by a novel group). Base units are maintained for complementarity with the appropriate polynucleotide target. Examples of such oligonucleotide mimetics include peptide nucleic acids (PNAs). US Patents that teach the preparation of PNA compounds include US Patent Nos. 5,539,082; 5,714,331 and 5,719,262, each of which is incorporated herein by reference. Is included, but is not limited thereto. Other backbone modifications that can be used in the present invention are disclosed in US Pat. No. 6,303,374.

  The oligonucleotides of the present invention may also include base modifications or substitutions. As used herein, “unmodified” or “natural” bases include the purine bases adenine (A) and guanine (G) and the pyrimidine bases thymine (T), cytosine (C), And uracil (U) are included. Modified bases include 5-methylcytosine (5-me-C), 5-hydroxymethylcytosine, xanthine, hypoxanthine, 2-aminoadenine, adenine and 6-methyl and other alkyl derivatives of guanine, adenine and guanine 2-propyl and other alkyl derivatives, 2-thiouracil, 2-thiothymine, and 2-thiocytosine, 5-halouracil and cytosine, 5-propynyluracil and cytosine, 6-azouracil, cytosine, and thymine, 5-uracil (sudouracil (sudouracil) ), 4-thiouracil, 8-halo, 8-amino, 8-thiol, 8-thioalkyl, 8-hydroxy, and other 8-substituted adenines and guanines, 5-halo (especially 5-bromo), 5-trifluoromethyl , And other 5-substituted uracils and cis But includes other synthetic and natural bases such as syn, 7-methylguanine and 7-methyladenine, 8-azaguanine and 8-azaadenine, 7-deazaguanine and 7-deazaadenine, and 3-deazaguanine and 3-deazaadenine. Not limited to these. Additional bases particularly useful for increasing the binding affinity of the oligomeric compounds of the invention include 5-substituted pyrimidines, 6-azapyrimidines, and N-2, N-6, and O-6 substituted purines (2-aminopropyladenine , 5-propynyluracil, and 5-propynylcytosine are included. 5-methylcytosine substitution has been shown to increase the stability of the nucleic acid duplex by 0.6-1.2 ° C., and this substitution is even more particularly the 2'-O-methoxyethyl sugar When combined with modifications, it is the presently preferred base substitution.

  Another modification of the oligonucleotides of the invention involves chemical coupling of one or more moieties or conjugates to the oligonucleotide to increase the activity, cellular distribution or cellular uptake of the oligonucleotide. Such moieties include lipid moieties such as cholesterol moieties, cholic acid, thioethers (eg, hexyl-S-tritylthiol), thiocholesterol, aliphatic chains as disclosed in US Pat. No. 6,303,374. (Eg dodecanediol or undecyl residue), phospholipids (eg dihexadecyl-rac-glycerol or triethylammonium 1,2-di-O-hexadecyl-rac-glycero-3-H-phosphonate), polyamine or polyethylene glycol chains Or adamantane acetic acid, palmityl moiety, or octadecylamine or hexylamino-carbonyl-oxycholesterol moiety, including but not limited to.

  It is not necessary that all positions of a given oligonucleotide molecule be uniformly modified, in fact, more than one of the above modifications may be incorporated into even one nucleotide within one compound or oligonucleotide.

  It is recognized that the oligonucleotides of the invention can be further modified for more effective use as a diagnostic and / or bioavailability, increased therapeutic efficacy and decreased cytotoxicity.

  In order to allow cellular expression of the polynucleotide of the invention, it is possible to use the nucleic acid construct of the invention which comprises at least the coding region of one of the above nucleic acid sequences and which further comprises at least one cis-acting regulatory element. As used herein, the phrase "cis-acting regulatory element" refers to a polynucleotide sequence, preferably a promoter, which binds to a trans-acting regulator and regulates transcription of a coding sequence present downstream thereof.

  Any suitable promoter sequence can be used with the nucleic acid constructs of the invention.

  Preferably, the promoter used by the nucleic acid construct of the invention is active in the transformed specific cell population. Examples of cell type specific and / or tissue specific promoters include the albumin promoter which is liver specific, the lymph specific promoter (Calame et al., (1988) Adv. Immunol. 43: 235-275), in particular Promoters for T cell receptor (Winoto et al., (1989) EMBO J. 8: 729-733) and immunoglobulins (Banerji et al. (1983) Cell 33729-740), neuron specific such as neurofilament promoter Promoter (Byrne et al. (1989) Proc. Natl. Acad. Sci. USA 86: 5473-5477), a pancreas specific promoter (Edlunch et al. (1985) Science 230). 912-916) or a mammary gland specific promoter (such as whey promoter (U.S. Pat. No. 4, 873, 316 and European Application Publication No. 264, 166), etc.). The nucleic acid construct of the present invention may further comprise an enhancer which is adjacent to or distal to the promoter sequence and which may function in the upregulation of transcription from the construct.

  The nucleic acid construct of the invention preferably further comprises a suitable selectable marker and / or an origin of replication. Preferably, the nucleic acid construct used is a shuttle vector, which both grow in E. coli (the construct contains an appropriate selectable marker and an origin of replication) and which is compatible with growth in optimal cells or integration in genes and tissues. . The constructs of the invention may be, for example, plasmids, bacmids, phagemids, cosmids, phages, viruses, or artificial chromosomes.

  Examples of suitable constructs include pcDNA3, pcDNA3.1 (+/-), pGL3, PzeoSV2 (+/-), pDisplay, pEF / myc / cyto, pCMV / myc / cyto (Invitrogen Co. (www. Invitrogen respectively). Commercially available from .com) but are not limited thereto. Examples of retroviral vectors and packaging systems are described by Clontech, San Diego, Calif. And are Retro-X vectors pLNCX and pLXSN, which can be cloned into multiple cloning sites, and transgenes are transcribed from the CMV promoter. Also included are vectors derived from Mo-MuLV such as pBabe, in which the transgene is transcribed from the 5 'LTR promoter.

  Currently preferred in vivo nucleic acid transfer techniques include transfection with viral or non-viral constructs such as adenovirus, lentivirus, herpes simplex virus type I, or adeno-associated virus (AAV), and lipid-based systems . Lipids useful for lipid-mediated transfer of genes are, for example, DOTMA, DOPE, and DC-Chol (Tonkinson et al., Cancer Investigation, 14 (1): 54-65 (1996)). The most preferred constructs for use in gene therapy are viruses, most preferably adenovirus, AAV, lentivirus or retrovirus. A viral construct, such as a retroviral construct, regulates gene expression by at least one transcriptional promoter / enhancer or locus defining element or other means such as alternative splicing, nuclear RNA transport, or post-translational modification of messengers Contains other elements that Such vector constructs will also, unless already present in the virus construct, the packaging signal appropriate for the virus used, the long terminal repeat (LTR) or part thereof, and the primer binding sites of the plus and minus strands. Including. In addition, such constructs typically include a signal peptide for secretion of the peptide from the host cell in which it is placed. Preferably, the signal sequence for this purpose is a mammalian signal sequence or a signal sequence of a polypeptide variant of the invention. Optionally, the construct may also include a signal that directs polyadenylation, as well as one or more restriction sites and a transcription termination sequence. By way of example, such constructs typically comprise a 5 'LTR, a tRNA binding site, a packaging signal, a double stranded DNA synthesis origin, and a 3' LTR, or a portion thereof. Other non-viral vectors such as cationic lipids, polylysine and dendrimers can be used.

Hybridization Assay The detection of a nucleic acid of interest in a biological sample can optionally be carried out by a hybridization based assay using oligonucleotide probes (non-limiting examples of probes of the invention are described above) .

  Traditional hybridization assays include PCR, RT-PCR, real-time PCR, RNase protection, in situ hybridization, primer extension, Southern blot (DNA detection), dot blot or slot blot (DNA, RNA), and Northern blot (RNA detection) (NAT-type assay is described in more detail below) is included. Recently, PNA has been described (Nielsen et al. 1999, Current Opin. Biotechnol. 10: 71-75). Other detection methods include kits and the like that include a probe on a dipstick mechanism.

  A hybridization based assay capable of detecting a variant of interest (ie, DNA or RNA) in a biological sample is 10, 15, 20 or 30 to 100 nucleotides long, preferably 10 to 50 nucleotides long, more preferably It depends on the use of oligonucleotides which may be 40-50 nucleotides in length.

  Thus, the isolated polynucleotide (oligonucleotide) of the invention is preferably capable of hybridizing to any of the nucleic acid sequences described herein under moderate to stringent hybridization conditions.

Moderate to stringent hybridization conditions include hybridization solutions containing 10% dextran sulfate, 1 M NaCl, 1% SDS, and 5 × 10 6 cpm of ³² P-labeled probe (65 ° C.), 0.2 × SSC and 0 Medium hybridization is characterized by 10% dextran sulfate, 1 M NaCl, 1% SDS, and 5 × 10 ⁶ cpm, as characterized by a final wash solution of 0.1% SDS and a final wash at 65 ° C. A hybridization solution containing a ³² P-labeled probe (65 ° C.), a final wash solution of 1 × SSC and 0.1% SDS, and a final wash at 50 ° C. are used.

  More generally, hybridization of short nucleic acids (less than 200 bp in length (eg, 17-40 bp in length)) can be performed using the following exemplary hybridization protocol, which can be corrected according to the desired stringency: (I) 6 × SSC and 1% SDS or 3 M TMACI, 0.01 M sodium phosphate (pH 6.8), 1 mM EDTA (pH 7.6), 0.5% SDS, 100 μg / ml denatured salmon sperm DNA, and 0 1% non-fat milk powder hybridization solution, hybridization temperature 1 to 1.5 ° C. lower than Tm, 3 M TMACI 1 to 1.5 ° C. lower than Tm, 0.01 M sodium phosphate (pH 6.8), Final wash solution of 1 mM EDTA (pH 7.6), 0.5% SDS, (ii) 6 × SSC and 0.1% Hybridization of DS or 3M TMACI, 0.01 M sodium phosphate (pH 6.8), 1 mM EDTA (pH 7.6), 0.5% SDS, 100 μg / ml denatured salmon sperm DNA, and 0.1% nonfat dry milk Solution, hybridization temperature 2 to 2.5 ° C. lower than Tm, 3 M TMACI at hybridization temperature 1 to 1.5 ° C. lower than Tm, 0.01 M sodium phosphate (pH 6.8), 1 mM EDTA (pH 7) .6) final wash solution of 0.5% SDS, final wash solution of 6 × SSC, and final wash at 22 ° C., (iii) 6 × SSC and 1% SDS or 3 M TMACI, 0.01 M sodium phosphate (PH 6.8), 1 mM EDTA (pH 7.6), 0.5% SDS, 100 μg / ml denatured salmon sperm DNA, and 0. 1% non-fat milk powder hybrid solution, hybridization temperature.

  Hybrid duplexes can be detected by a number of methods. Typically, the hybrid duplex is separated from non-hybridizing nucleic acid and the label bound to the duplex is detected. Such labels refer to radioactive, fluorescent, biological, or enzymatic tags or labels that are commonly used in the art. The label can be conjugated to either an oligonucleotide probe or nucleic acid from a biological sample.

  Probes can be labeled by a number of well known methods. Non-limiting examples of radioactive labels include 3H, 14C, 32P, and 35S. Non-limiting examples of detectable markers include ligands, fluorophores, chemiluminescers, enzymes, and antibodies. Other detectable markers for use with probes that can increase the sensitivity of the methods of the invention include biotin and radioactive nucleotides. It will be apparent to one skilled in the art that the choice of a particular label will determine the manner in which it binds to the probe.

  For example, by incorporation of biotinylated dNTPs or rNTPs or some similar means (eg photocrosslinking of psoralen derivatives of biotin to RNA) and subsequent addition of labeled streptavidin (eg phycoerythrin conjugated streptavidin) or equivalent The oligonucleotides of the invention can be labeled after synthesis. Alternatively, when using a fluorescently labeled oligonucleotide probe, fluorescein, lissamine, phycoerythrin, rhodamine (Perkin Elmer Cetus), Cy2, Cy3, Cy3.5, Cy5, Cy5.5, Cy7, FluorX (Amersham), etc. (eg, Kricka et al. (1992), Academic Press San Diego, Calif.) Can be attached to oligonucleotides.

  One skilled in the art recognizes that washing steps are used to wash away excess target DNA or probe and unbound conjugate. In addition, standard heterogeneous assay formats are suitable for detection of hybrids using labels present on oligonucleotide primers and probes.

  It is recognized that various controls can be usefully used to improve the accuracy of the hybridization assay. For example, the sample can be hybridized with an irrelevant probe and treated with RNase A prior to hybridization to assess pseudohybridization.

  Although the present invention does not particularly rely on the use of a label for the detection of a particular nucleic acid sequence, such a label may be advantageous as it increases the detection sensitivity. In addition, the labeling allows automation. Probes can be labeled by a number of well known methods.

As is commonly known, radioactive nucleotides can be incorporated into the probes of the invention by several methods. Non-limiting examples of radioactive labels include ³ H, ¹⁴ C, ³² P, and ³⁵ S.

  One skilled in the art will recognize that washing steps can be used to wash away excess target DNA or probe and unbound conjugate. In addition, standard heterogeneous assay formats are suitable for detection of hybrids using labels present on oligonucleotide primers and probes.

  It is recognized that various controls can be usefully used to improve the accuracy of the hybridization assay.

  The probes of the invention can be used with naturally occurring sugar-phosphate backbones as well as modified backbones, including phosphorothioates, dithionates, alkyl phosphonates, and a-nucleotides. The probes of the invention can be constructed from ribonucleic acid (RNA) or deoxyribonucleic acid (DNA) (preferably DNA).

NAT Assay The nucleic acid of interest in a biological sample can optionally be detected by a NAT-based assay that includes nucleic acid amplification technology such as, for example, PCR (eg, variations thereof such as real-time PCR).

  As used herein, a "primer" is a double-stranded region that can anneal (hybridize) to a target sequence, thereby serving as a starting point for DNA synthesis under appropriate conditions. It is defined as an oligonucleotide that can be produced.

  Selected sequences, target sequences, or nucleic acid sequences can be amplified by a number of suitable methods. In general, Kwoh et al. , 1990, Am. Biotechnol. Lab. See 8:14. A large number of amplification techniques have been described and can be easily adapted to meet the specific needs of the person skilled in the art. Non-limiting examples of amplification techniques include polymerase chain reaction (PCR), ligase chain reaction (LCR), strand displacement amplification (SDA), transcription based amplification, q3 replicase system, and NASBA (Kwoh et al. USA, 1989, Proc. Nat I. Acad. Sci. USA 86, 1173-1177; Lizardi et al., 1988, BioTechnology 6: 1197-1202; Malek et al., 1994, Methods Mol. Biol., 28: 253-. 260; and Sambrook et al., 1989, supra).

  The term "amplification pair" (or "primer pair") is used herein as it is used together in amplification of a selected nucleic acid sequence by one of a number of amplification process types, preferably polymerase chain reaction. Refers to the selected oligonucleotide (oligo) pair of the present invention. Other types of amplification processes include ligase chain reaction, strand displacement amplification, or nucleic acid sequence based amplification, as described in more detail below. The oligos are designed to bind to the complementary sequence under selected conditions, as is generally known in the art.

  In one particular embodiment, amplification of a nucleic acid sample from a patient is amplified under conditions that favor amplification of the most abundant differentially expressed nucleic acid. In one preferred embodiment, RT-PCR is performed on mRNA samples from patients under conditions that favor amplification of the most abundant mRNA. In another preferred embodiment, amplification of differentially expressed nucleic acids is performed simultaneously. It is understood by one skilled in the art that such methods can be adapted to the detection of differentially expressed proteins instead of differentially expressed nucleic acid sequences.

  Nucleic acids (ie, DNA or RNA) for carrying out the present invention can be obtained by known methods.

  The oligonucleotide primers of the invention may be of any suitable length, depending on the particular assay format used, the particular needs, and the genome targeted. Optionally, the oligonucleotide primers are at least 12 nucleotides in length, preferably between 15 and 24 molecules, which can be adapted to be particularly suitable for the chosen nucleic acid amplification system. As is commonly known in the art, an oligonucleotide primer can be designed by considering the melting point of its hybridization to its targeted sequence (Sambrook et al., 1989, Molecular Cloning-A Laboratory Manual Ausubel et al., 1989, in Current Protocols in Molecular Biology, John Wiley & Sons Inc., N. Y.).

  It is recognized that antisense oligonucleotides can be used to quantify the expression of the splice isoform of interest. Such detection is performed at the pre-mRNA level. In essence, the ability to quantify transcription from the splice site of interest can be influenced by the accessibility of the splice site. Oligonucleotides can compete with splice factor sequences for splice site sequences. Thus, low antisense oligonucleotide activity indicates splicing activity.

  Polymerase chain reactions and other nucleic acid amplification reactions are well known in the art (various non-limiting examples of these reactions are described in more detail below). The oligonucleotide pairs of the aspects of the invention are preferably matched melting point (Tm) (eg less than 7 ° C., preferably less than 5 ° C., more preferably less than 4 ° C., most preferably less than 3 ° C., ideally It is chosen to have different melting points) between 3 ° C and 0 ° C.

  Polymerase chain reaction (PCR): Mullis and Mullis et al. Polymerase chain reaction (PCR), as described in US Pat. Nos. 4,683,195 and 4,683,202, assigned to the assignee of the present invention, targets in a mixture of genomic DNA without cloning and purification. It is a method of increasing the concentration of segments of the sequence. This technology provides one approach to the problem of low target sequence concentration. PCR can be used to directly increase the target concentration to easily detectable levels. The process of amplification of this target sequence involves the transfer of a 1 molar excess of two oligonucleotide primers in which each strand of the double stranded target sequence and the DNA mixture containing the desired target sequence are complementary. The mixture is denatured and then hybridized. After hybridization, the primers are extended with a polymerase to form a complementary strand. The steps of denaturation, hybridization (annealing), and polymerase extension (extension) can be repeated as necessary to obtain a relatively high concentration of segments of the desired target sequence.

  This length is a tunable parameter, as the length of the segment of the desired target sequence is determined by the relative position of the primers relative to one another. These are considered "PCR amplified" because the segments of the desired target sequence become the predominant sequences (in terms of concentration) in the mixture.

  Ligase chain reaction (LCR or LAR): Ligase chain reaction (LCR; sometimes referred to as "ligase amplification reaction" (LAR)) has evolved into another well-recognized method of nucleic acid amplification. In LCR, four oligonucleotides, two flanking oligonucleotides that specifically hybridize to one strand of target DNA, and a complementary set of flanking oligonucleotides that hybridize to the opposite strand are mixed, and DNA ligase is added to the mixture Do. The ligase is covalently linked to each hybridized pair of molecules if they are completely complementary at the junction point. Importantly, in LCR, the two probes ligate to each other only if they form a base pair with the sequence in the target sample without gaps or mismatches. Repeated cycles of denaturation and ligation amplify short segments of DNA. LCR has also been used in combination with PCR to enhance detection of single base changes (see, eg, Segev, PCT Publication No. W09001069 A1 (1990)). However, as the four oligonucleotides used in this assay can be paired to form two short ligatable fragments, a background signal independent of the target may be generated. The use of LCRs for mutant screening is limited to the testing of specific nucleic acid positions.

  Self-Sustained-Synthetic-Reaction (3SR / NASBA): Self-maintaining Sequence Replication Reaction (3SR) is a transcription-based in vitro amplification that can exponentially amplify RNA sequences at constant temperature It is a system. The amplified RNA can then be used for mutation detection. In this method, an oligonucleotide primer is used to add a phage RNA polymerase promoter to the 5 'end of the sequence of interest. For a cocktail of enzyme and substrate containing a second primer, reverse transcriptase, RNase H, RNA polymerase, and ribo- and deoxyribonucleotide triphosphates, the target sequence is a round of transcription, cDNA synthesis, and second strand synthesis. Is repeated to amplify the region of interest. The use of 3SR to detect mutations is kinetically limited to the screening of small segments of DNA (e.g. 200-300 base pairs).

  Q-beta (Qβ) replicase: In this method, a probe that recognizes the sequence of interest is attached to a replicable RNA template for Qβ replicase. The use of a sequence specific ligation step addressed the major issues previously identified for false positives due to replication of non-hybridizing probes. However, ligation must be performed at low temperature (37 ° C.) with T4 DNA ligase since the available thermostable DNA ligase is not effective for this RNA substrate. This avoids the use of high temperature as a means of achieving specificity as in LCR, and ligation events can be used to detect mutations at the ligation site but not elsewhere.

  Successful diagnostic methods should be very specific. A method of modulation of the specificity of easy nucleic acid hybridization is by modulation of the reaction temperature. While 3SR / NASBA and Qβ can all produce large amounts of signal, one or more enzymes involved can not be used at high temperature (ie above 55 ° C.). Therefore, the reaction temperature can not be raised to avoid nonspecific hybridization of the probe. If you shorten the probe to melt the probe more easily at low temperatures, the possibility of obtaining more than one perfect match in complex genomes increases. For these reasons, PCR and LCR are currently at the center of research in detection technology.

The basis of the amplification procedure in PCR and LCR is the fact that the product of one cycle becomes a usable template for all subsequent cycles, thereby doubling the population with each cycle. The final yield of any such doubling system can be expressed as: (1 + X) ⁿ = y, where “X” is the average efficiency (copy rate at each cycle), "N" is the number of cycles and "y" is the overall efficiency or reaction yield). When each target DNA copy is used as a template in each polymerase chain reaction cycle, the average efficiency is 100%. When performing PCR of 20 cycles, the yield is ^{2 20} (i.e., 1,048,576 times copies of the starting material). If the reaction conditions reduce the average efficiency to 85%, the yield of 20 cycles is only 1.85 ²⁰ (ie 220,513 copies of the starting material). In other words, performing PCR at 85% efficiency yields only 21% of the final product as compared to running reaction at 100% efficiency. For reactions where the average efficiency is reduced to 50%, less than 1% of possible products.

  In practice, it is rare to achieve theoretical maximum yields in routine polymerase chain reactions, and PCR is usually performed for more than 20 cycles to compensate for lower yields. With an average efficiency of 50%, 34 cycles are required to achieve a million-fold amplification in 20 cycles in theory, and with lower efficiencies the number of cycles required is very high. In addition, any background product that amplifies with an average efficiency higher than the intended target will be the major product.

  Also, numerous variables (including target DNA length and secondary structure, primer length and design, primer and dNTP concentrations, buffer composition, etc.) affect the average efficiency of PCR. Can be given. Contamination or cross-contamination of reactions with exogenous DNA (eg, DNA that has spilled over the surface of a laboratory) is also a primary consideration. The reaction conditions for each different primer pair and target sequence must be carefully optimized, and even experienced researchers can take several days for this process. The difficulty of this process, which includes numerous technical considerations and other factors, is a major drawback in the use of PCR for clinical purposes. In fact, PCR has not yet entered the clinical market in a significant manner. Similar concerns arise with LCR as LCR must also be optimized to use different oligonucleotide sequences for each target sequence. Furthermore, both methods require expensive equipment to enable accurate temperature cycling.

  Many applications of nucleic acid detection technology, such as in the study of allelic variation, include not only the detection of specific sequences in complex backgrounds, but also the discrimination of sequences that differ by a few or one nucleotide. One method of detecting allele-specific variants by PCR is based on the fact that it is difficult for Taq polymerase to synthesize DNA strands in the presence of a mismatch between the template strand and the 3 'end of the primer. . Allele-specific variants can be detected by the use of primers that are completely compatible with only one possible allele, and mismatches with other alleles act to avoid primer extension. , Thereby avoiding amplification of this sequence. This method is substantially limited in that the base composition of the mismatch affects the ability to avoid extension beyond the mismatch, and certain mismatches do not avoid or have minimal effect on extension.

  Use a similar 3 'mismatch strategy that is more effective at avoiding ligation in LCR. While any mismatch effectively blocks the action of the thermostable ligase, LCR still has the disadvantage that target-independent background ligation products initiate amplification. Furthermore, it is clear that the combination of PCR to identify the nucleotide at each position and the subsequent LCR is also difficult to handle in the clinical laboratory.

  The direct detection method of the various preferred embodiments of the present invention may be, for example, cycling probe reaction (CPR) or branched DNA analysis.

  If the amount of detection of the available nucleic acid is sufficient, it has the advantage that this sequence is detected directly instead of making more copies of the target (eg in the case of eg PCR and LCR). More notably, methods that do not amplify the signal exponentially are better for quantitative analysis. Even when the signal is enhanced by the binding of multiple dyes to one oligonucleotide, the final signal intensity and target amount are directly correlated. Such a system has the further advantage that the reaction product itself does not promote further reactions, whereby the contamination of the laboratory surface by the product is not so great as to be concerned. Recently devised techniques seek to eliminate the use of radioactivity and / or have improved sensitivity in a form that can be automated. Two examples are "cycling probe reaction" (CPR) and "branched DNA" (bDNA).

  Cycling Probe Reaction (CPR): The Cycling Probe Reaction (CPR) uses a long chimeric oligonucleotide, the central part of which is made from RNA and the two ends made of DNA. Hybridization of the probe to the target DNA and exposure to the thermostable RNase H digest the RNA portion. This destabilizes the remaining DNA portion of the duplex, releasing the rest of the probe from the target DNA, and another probe molecule repeats the process. Signals in the form of cleaved probe molecules accumulate at a linear rate. While the iterative process increases the signal, the RNA portion of the oligonucleotide is vulnerable to RNase which can be retained throughout sample preparation.

  Branched DNA: Branched DNA (bDNA) includes oligonucleotides of a branched structure in which each oligonucleotide can carry 35-40 labels (e.g., alkaline phosphatase enzyme). While this enhances the signal from hybridization, the signal for nonspecific binding also increases.

  Changes in at least one sequence of various preferred embodiments of the present invention can be made, for example, restriction fragment length polymorphism (RFLP analysis), allele specific oligonucleotide (ASO) analysis, denaturing / temperature gradient gel electrophoresis (DGGE / TGGE), single-strand conformation polymorphism (SSCP) analysis, or can be detected by dideoxy fingerprinting (ddF).

  The need for tests that can detect specific nucleic acid sequences and sequence variations is rapidly increasing in clinical diagnostics. With the accumulation of nucleic acid sequence data for genes from humans and pathogenic organisms, so far there has been a rapid demand for rapid, cost-effective and easy-to-use tests for mutations within specific sequences. It is increasing.

  Only a handful of methods have been devised to scan nucleic acid segments for mutations. Determining the entire gene sequence of each test sample (eg, a bacterial isolate) is one option. For sequences of less than about 600 nucleotides, this can be done using amplification material (eg, PCR reaction products). This avoids the time and expense associated with cloning the segment of interest. However, specialized equipment and highly trained personnel are required, and this method is very laborious and expensive, so it is not practical and effective for clinical purposes.

  Given the difficulties associated with sequencing, a given segment of nucleic acid can be characterized at several other levels. At the lowest resolution, the size of the molecule can be determined by electrophoresis by comparison with the migration of a known standard on a sample gel. Cleavage with a combination of restriction enzymes prior to electrophoresis can give a more detailed picture of the molecule and construct an ordered map. The presence of a specific sequence within the fragment can be detected by hybridization of the labeled probe, or the correct nucleotide sequence, primers in the presence of partial chemical degradation or chain-terminating nucleotide analogues It can be determined by extension.

  Restriction fragment length polymorphism (RFLP): Detection of single base differences between similar sequences often requires analysis at the highest resolution. For cases where the position of the nucleotide in question is previously known, several methods have been developed to test single base changes without direct sequencing. For example, changes in digestion patterns can be used as a diagnostic tool if the mutation of interest occurs within the limits of the recognition sequence (eg, restriction fragment length polymorphism (RFLP) analysis).

  One point mutation has also been detected by making or destroying RFLP. Mutations are detected and localized by the presence and size of the RNA fragments generated by cleavage at the mismatch. In general, when using another strategy to detect single base substitutions, termed "mismatch chemical cleavage" (MCC), one nucleotide mismatch in the DNA heteroduplex may be a number of chemicals. Also recognize and disconnect. However, this method requires osmium tetroxide and piperidine, which are very toxic compounds, and their use in clinical laboratories is not appropriate.

  RFLP analysis is less sensitive and requires large samples. When RFLP analysis is used for the detection of point mutations, by its nature it is limited to the detection of only single base changes contained within the restriction sequences of known restriction endonucleases. In addition, most available enzymes recognize sequences of 4 to 6 base pairs and are cleaved too often for large scale DNA manipulations. Thus, while applicable only in the case of small fragments, most mutations are not within the scope of such sites.

  A handful of rare-cutting restriction enzymes that specifically recognize 8 base pairs have been isolated and are widely used for gene mapping, but these enzymes are few and G + C rich sequences The site is restricted to the recognition of and tends to be highly clustered. Recently, endonucleases encoded by group I introns showing specificity for more than 12 base pairs have been discovered, but these are few.

  Allele-Specific Oligonucleotide (ASO): Allele for hybridisation near a mutated nucleotide, so that primer extension or ligation events can be used as an indicator of a match or mismatch if the recognition sequence does not change. Gene specific oligonucleotides (ASO) can be designed. Hybridization using radioactively labeled allele specific oligonucleotides (ASO) has also been applied to the detection of specific point mutations. This method is based on the differences in melting temperatures of short DNA fragments that differ by one nucleotide. Mutations and wild-type alleles can be distinguished by stringent hybridization and wash conditions. The ASO approach applied to PCR products is also widely used by many researchers to detect and characterize point mutations in ras genes and gsp / gip oncogenes. As there are different nucleotide changes at multiple positions, the ASO method requires the use of multiple oligonucleotides to cover all possible oncogene mutations.

  The use of any of the above techniques (i.e. RFLP and ASO) must know the exact location where the mutation is suspected before testing. In other words, these techniques are not applicable if it is necessary to detect the presence of mutations in the gene or sequence of interest.

  Denaturing / Temperature Gradient Gel Electrophoresis (DGGE / TGGE): Two other methods rely on detection of changes in electrophoretic mobility in response to small sequence changes. Of these methods, "denaturing / temperature gradient gel electrophoresis" (DGGE) is based on the finding that slightly different sequences show different local melting patterns when separated by electrophoresis on gradient gels. In this manner, the difference in melting characteristics of homoduplex and heteroduplex in one nucleotide can detect the presence of a mutation, by corresponding to changes in its electrophoretic mobility, thus distinguishing variants. can do. The fragment to be analyzed (usually the PCR product) is "clamped" to one end of a long stretch (30-80) of G-C base pairs to completely denature the desired sequence without completely dissociating the strand Let The binding of the GC "clamp" to the DNA fragment increases the mutated fragment and can be recognized by DGGE. Binding of the GC clamp to one primer is important to ensure that the dissociation temperature of the amplified sequence is lowered. The technique is improved using a temperature gradient, and this method can also be applied to RNA: RNA duplexes.

  Having to optimize denaturing conditions for each DNA type to be tested limits the use of DGGE. In addition, this method requires a dedicated device to prepare the gel and maintain the high temperature required during electrophoresis. The cost associated with the synthesis of the tail clamped to one oligonucleotide of each sequence to be tested is also a major consideration. Furthermore, DGGE requires long migration times. The long migration time of DGGE was shortened by a modified version of DGGE called constant denaturant gel electrophoresis (CDGE), which under different denaturing conditions to increase the effectiveness of mutation detection. It is necessary to migrate.

  A similar technique to DGGE, called temperature gradient gel electrophoresis (TGGE), uses a temperature gradient rather than a chemical denaturation gradient. TGGE requires the use of specialized equipment capable of producing a temperature gradient oriented perpendicular to the electric field. TGGE can detect mutations in relatively small DNA fragments, which requires the use of multiple PCR products prior to gel migration for scanning of large gene segments.

  Single Strand Conformational Polymorphism (SSCP): Another common method, referred to as "single-strand conformation polymorphism" (SSCP), was developed by Hayashi, Sekya and colleagues, and this method is Based on the observation that the nucleic acid strand of can take a characteristic higher-order structure under native conditions, and these higher-order structures affect the electrophoretic mobility. Complementary strands are expected to have sufficiently different structures, and one strand can be separated from the other. Sequence variations within fragments also alter conformations, thereby altering mobility, which can be used as an assay for sequence variation.

  The SSCP process is a slow electrophoresis on a native polyacrylamide gel so that denaturation of the DNA segment (eg, PCR product) labeled on both strands and intramolecular interaction may occur but does not prevent migration. Including separation by This technique is very sensitive to variations in gel composition and temperature. This method is very limited by the relative difficulty of comparing data obtained at different laboratories under apparently similar conditions.

  Dideoxy fingerprinting (ddF): Dideoxy fingerprinting (ddF) is another technique developed to scan genes for the presence of mutations. The ddF technology combines the components of Sanger dideoxy sequencing and SSCP. The dideoxy sequencing reaction is performed using one dideoxy terminator, and then the reaction product is electrophoresed on a native polyacrylamide gel to detect changes in the mobility of the termination segment as in SSCP analysis. While ddF is an improvement over SSCP with respect to increased sensitivity, ddF requires the use of expensive dideoxynucleotides, and this technique has the appropriate size for SSCP (ie for optimal detection of mutations). Analysis of fragments of 200 to 300 bases).

  In addition to the above limitations, all these methods are limited to the size of nucleic acid fragments that can be analyzed. Direct sequencing approaches require more than 600 base pairs of sequence for cloning, so that it takes time and expense for either detection subcloning or primer walking to cover all fragments. SSCP and DGGE are more strictly limited in size. These methods are considered unsuitable for larger fragments, as changes in sequence reduce sensitivity. Although SSCPs are reportedly able to detect 90% single base substitutions of 200 base pair fragments, detection decreases to less than 50% for 400 base pair fragments. Similarly, the sensitivity of DGGE decreases when the fragment length reaches 500 base pairs. The ddF technique, which combines direct sequencing and SSCP, is also limited to the relatively small size of DNA that can be screened.

  According to the presently preferred embodiment of the present invention, the step of searching for any of the nucleic acid sequences described herein in tumor cells or cells from cancer patients is carried out by the following appropriate techniques: Nucleic Acid Sequencing Polymerase chain reaction, ligase chain reaction, autonomous synthesis reaction, Qβ-replicase, cycling probe reaction, branched DNA, restriction fragment length polymorphism analysis, chemical cleavage of mismatch, heteroduplex analysis, allele specific oligonucleotide These include, but are not limited to, denaturing gradient gel electrophoresis, constant denaturant gel electrophoresis, temperature gradient gel electrophoresis, and dideoxy fingerprinting.

  It can also be optionally detected using a chip or other such device. It is preferred that the nucleic acid sample containing the candidate region to be analyzed is isolated, amplified and labeled with a reporter group. The reporter group may be a fluorescent group such as phycoerythrin. The labeled nucleic acid is then incubated with the probes immobilized on the chip using a fluidics station, and the construction of fluidics devices in silicon and glass substrates, in particular microcapillary devices, is described.

  Once the reaction is complete, insert the tip into a scanner and detect the hybridization pattern. Hybridization data is collected as the signal emitted from the reporter group that is already incorporated into the nucleic acid and is now attached to the probe attached to the chip. Knowing the sequence and position of each probe immobilized on the chip, the identity of the nucleic acid hybridizing to a given probe can be determined.

  When used in conjunction with an automated device, it is recognized that the above detection methods can be used to rapidly and easily screen multiple samples for disease and / or pathological conditions.

Amino Acid Sequencing and Peptides The terms "polypeptide", "peptide" and "protein" are used interchangeably herein to refer to a polymer of amino acid residues. The term applies to amino acids in which one or more amino acid residues are analogs or mimetics of the corresponding naturally occurring amino acids and polymers of naturally occurring amino acids. The polypeptide can be modified, for example, by the addition of carbohydrate residues to form a glycoprotein. The terms "polypeptide", "peptide" and "protein" include glycoproteins as well as non-glycoproteins.

  Polypeptide products can be biochemically synthesized by use of standard solid phase techniques and the like. Such methods include, but are not limited to, exclusive solid phase synthesis, partial solid phase synthesis methods, fragment degeneracy, classical liquid synthesis. These methods may be used where the peptide is relatively short (ie 10 kDa) and / or can not be produced recombinantly (ie not encoded by the nucleic acid sequence), thereby comprising different chemical properties. It is preferred to use.

  Solid phase polypeptide synthesis procedures are well known in the art and are further described in John Morrow Stewart and Janis Dillaha Young, Solid Phase Peptide Syntheses (2nd Ed., Pierce Chemical Company, 1984).

  The synthetic polypeptide is optionally purified by preparative high performance liquid chromatography (Creighton T. (1983) Proteins, structures and molecular principles. WH Freeman and Co. N. Y.) and then its composition is amino acid sequencing. It can be confirmed by

  If large amounts of polypeptide are desired, the polypeptide may be modified as described by Bitter et al. , (1987) Methods in Enzymol. 153: 516-544, Studier et al. (1990) Methods in Enzymol. 185: 60-89, Brisson et al. (1984) Nature 310: 511-514, Takamatsu et al. (1987) EMBO J. 6: 307-311, Coruzzi et al. (1984) EMBO J. 3: 1671-1680 and Brogli et al. (1984) Science 224: 838-843, Gurley et al. (1986) Mol. Cell. Biol. 6: 559-565 and Weissbach & Weissbach, 1988, Methods for Plant Molecular Biology, Academic Press, NY, Section VIII, pp 421-463 and the like.

  The invention also includes the polypeptides encoded by the polynucleotide sequences of the invention and polypeptides according to the amino acid sequences as described herein. The invention also includes homologs of these polypeptides, such homologs being at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80% of the amino acid sequence %, At least 85%, at least 95%, or even 100% homologous, but using BlastP software from the National Center of Biotechnology Information (NCBI) using default parameters, optionally and preferably including Can be determined: filtering is on (this option filters repetitive or low complexity sequences from queries using the Seg (protein) program , Scoring matrix for proteins is BLOSUM62, word size is 3, E value is 10, gap costs are 11,1 (initialization and extension), the alignment number of display is 50. Optionally, the identity / homology of the nucleic acid sequences can be determined by use of the BlastN software of the National Center of Biotechnology Information (NCBI), which preferably uses the DUST filter program, preferably , E-values of 10, filtering low complexity arrays, word size is 11. Finally, the invention also relates to fragments and mutations of the above polypeptides (deletions, insertions, or deletion of one or more naturally occurring or artificially derived amino acids in a random or targeted manner Including polypeptides having substitutions, etc.).

  The peptides identified by the present invention are degradation products, synthetic peptides or recombinant peptides and peptidomimetics, typically, for example, making the peptide more stable while allowing more penetration of the peptide into the body or cells It is recognized that it may be a synthetic peptide that may have a modification to make peptoids and peptide analogs that are peptoids and semipeptoids. Such modifications include N-terminal modification, C single modification, peptide bond modification (CH2-NH, CH2-S, CH2-S = O, O = C-NH, CH2-O, CH2-CH2, S = C-NH, CH = CH, or CF = CH, including, but not limited to, backbone modifications, and residue modifications, including, but not limited to. Methods for preparing peptidomimetic compounds are well known in the art and are specified. Further details regarding this are described below.

  The peptide bond (-CO-NH-) in the peptide is, for example, N-methylated bond (-N (CH3) -CO-), ester bond (-C (R) H-C-O-O-C ( R) -N-), ketomethylene bond (-CO-CH2-), α-aza bond (-NH-N (R) -CO-) (wherein R is any alkyl (eg, methyl)) , Carba (carba) bond (-CH 2 -NH-), hydroxyethylene bond (-CH (OH)-CH 2-), thioamide bond (-CS-NH-), olefin double bond (-CH = CH-), Retroamide bond (-NH-CO-), peptide derivative (-N (R) -CH2-CO-), wherein R is a "normal" side chain naturally occurring at the carbon atom It can be replaced.

  These modifications may occur simultaneously with any, or even some (2-3) of linkages along the peptide chain.

  Natural aromatic amino acids (Trp, Tyr and Phe) to non-natural acids such as phenylglycine, TIC, naphthylelanine, ring methylated derivatives of Phe, halogenated derivatives of Phe, or o-methyl-Tyr It can be replaced.

  In addition to the above, the peptides of the invention may also include one or more modified amino acids or one or more non-amino acid monomers (eg fatty acids, complex carbohydrates etc).

  As used in the specification and claims that follow, the term "amino acid" refers to the twenty naturally occurring amino acids (these amino acids are often post-translationally modified in vivo (eg, hydroxyproline) (Including phosphoserine and phosphothreonine) and unusual amino acids (including but not limited to 2-aminoadipate, hydroxylysine, isodesmosine, norvaline, norleucine and ornithine) Be understood. Furthermore, the term "amino acid" includes D- and L-amino acids.

  Preferably, one or more non-natural or natural polar amino acids (whose hydroxyl groups are included) are preferably used in the peptide of the invention, since it is preferred to use the peptide of the invention in diagnostics where the peptide in soluble form is required. These include, but are not limited to, serine and threonine, which can increase the solubility of the peptide by the side chain.

  It is preferred to use the peptides of the invention in linear form, but it is recognized that if the cyclisation does not significantly interfere with the peptide properties, it is also possible to use cyclised forms of the peptide.

  The peptides of the invention can be biochemically synthesized by use of standard solid phase techniques and the like. These methods include exclusive solid phase synthesis, partial solid phase synthesis methods, fragment degeneracy, classical liquid synthesis well known in the art. These methods may be used where the peptide is relatively short (ie 10 kDa) and / or can not be produced recombinantly (ie not encoded by the nucleic acid sequence), thereby comprising different chemical properties. It is preferred to use.

  Synthetic peptides can be purified by preparative high performance liquid chromatography and their composition can be confirmed by amino acid sequencing.

  When large amounts of the peptide of the present invention are desired, the peptide of the present invention can be used as described in Bitter et al. , (1987) Methods in Enzymol. 153: 516-544, Studier et al. (1990) Methods in Enzymol. 185: 60-89, Brisson et al. (1984) Nature 310: 511-514, Takamatsu et al. (1987) EMBO J. 6: 307-311, Coruzzi et al. (1984) EMBO J. 3: 1671-1680 and Brogli et al. (1984) Science 224: 838-843, Gurley et al. (1986) Mol. Cell. Biol. 6: 559-565 and Weissbach & Weissbach, 1988, Methods for Plant Molecular Biology, Academic Press, NY, Section VIII, pp 421-463, etc. and can also be produced using recombinant techniques as described above.

Antibody "Antibody" preferably refers to a polypeptide substantially encoded by an immunoglobulin gene or a fragment thereof that specifically binds and recognizes an epitope (e.g. an antigen). The recognized immunoglobulin genes include the kappa and lambda light chain constant region genes, the alpha, gamma, delta, epsilon, and mu heavy chain constant region genes, as well as the myriad immunoglobulin variable region genes. Antibodies exist, eg, as intact immunoglobulins or as a number of well-characterized fragments produced by digestion with various peptidases. This includes, for example, Fab ′ and F (ab) ′ ₂ fragments. As used herein, the term "antibody" also includes antibody fragments that are produced by modification of whole antibodies or synthesized de novo using recombinant DNA methods. Antibodies also include polyclonal antibodies, monoclonal antibodies, chimeric antibodies, humanized antibodies, or single chain antibodies. The "Fc" portion of an antibody refers to that portion of an immunoglobulin heavy chain that contains one or more heavy chain constant regions (CH1, CH2, and CH3) but does not include the heavy chain variable region.

  Functional fragments of antibodies capable of binding to macrophages (Fab, F (ab ') 2 and Fv etc.) are described below: (1) Fab: containing a monovalent antigen-binding fragment of an antibody molecule, intact Fragments that can be produced by digestion of whole antibodies with the enzyme papain to obtain part of the light chain and one heavy chain, (2) Fab ': to obtain parts of the intact light chain and heavy chain (3) (Fab ′) 2: Enzyme pepsin, which is a fragment of an antibody molecule obtainable by treatment of the whole antibody with pepsin and subsequent reduction, wherein two Fab ′ fragments are obtained per antibody molecule. A fragment of the antibody that can be obtained without treatment with whole antibody and then (Fab ′) 2 has two disulfide bonds (4) Fv: defined as a genetically engineered fragment comprising the light chain variable region and the heavy chain variable region expressed as two chains, thus being a dimer of two Fab ′ fragments held together (5) Single-chain antibody ("SCA"): A genetically engineered molecule comprising a light chain variable region and a heavy chain variable region linked by a suitable polypeptide linker as a single chain molecule fused to a gene .

  Methods of producing polyclonal and monoclonal antibodies and fragments thereof are well known in the art (e.g. Harlow and Lane, Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory, New York, 1988 (incorporated herein by reference). See)).

  The antibody fragments of the invention may be prepared by proteolytic hydrolysis of the antibodies or expression of DNA encoding the fragments in E. coli or mammalian cells (eg, Chinese hamster ovary cell culture or other protein expression systems) it can. Antibody fragments can be obtained by pepsin or papain digestion of whole antibodies by conventional methods. For example, antibody fragments can be produced by enzymatic cleavage of antibodies with pepsin, thereby obtaining a 5S fragment designated F (ab ') 2. This fragment can be further cleaved using a thiol reducing agent to optionally protect the sulfhydryl group resulting from cleavage of the disulfide bond to produce a monovalent 3.5S Fab 'fragment. Alternatively, enzymatic cleavage using pepsin produces two monovalent Fab 'fragments and Fc fragments directly. These methods are described, for example, in US Pat. Nos. 4,036,945 and 4,331,647 to Goldenberg and the references contained therein (these patents are herein incorporated by reference in their entirety). Is incorporated by reference). Porter, R .; R. [Biochem. J. 73: 119-126 (1959)]. Separation of heavy chain to form monovalent light chain-heavy chain fragment, further cleavage of fragment, or additional enzymatic, chemical, or gene so long as the fragment binds to the antigen recognized by the intact antibody Other antibody cleavage methods, such as techniques, can also be used.

  Fv fragments comprise an association of VH and VL chains. Inbar et al. [Proc. Nat'l Acad. Sci. This association may be nonpolar, as described in USA 69: 2659-62 (19720) Alternatively, the variable chains can be linked by crosslinking with intermolecular disulfide bonds or chemicals such as glutaraldehyde Preferably, the Fv fragment comprises VH and VL chains linked by a peptide linker These single chain antigen binding proteins (sFv) comprise DNA sequences encoding VH and VL domains linked by an oligonucleotide The structural gene is prepared by construction of a structural gene, which is then inserted into an expression vector and then transferred into a host cell such as E. coli etc. The recombinant host cell is a single polypeptide with a linker peptide bridging the two V domains. For example, the method for producing sFv is hitlow and Filpula, Methods 2: 97-105 (1991); Bird et al., Science 242: 423-426 (1988); Pack et al., Bio / Technology 11: 1271-77 (1993); No. 4,946,778, which is incorporated herein by reference in its entirety.

  Another form of antibody fragment is a peptide encoding one complementarity determining region (CDR). CDR peptides ("minimal recognition units") can be obtained by construction of a gene encoding a CDR of an antibody of interest. Such genes are prepared, for example, by synthesizing variable regions from RNA of antibody producing cells using polymerase chain reaction (see, eg, Larrick and Fry [Methods, 2: 106-10 (1991)]. ).

  The humanized form of the non-human (eg, murine) antibody is a chimeric molecule of an immunoglobulin comprising a minimal sequence derived from a non-human immunoglobulin, an immunoglobulin chain, or a fragment thereof (Fv, Fab, Fab ', F (ab') Or other antigen binding subsequences of an antibody, etc.). For humanized antibodies, residues from non-human species such as mice, rats, or rabbits, having the desired specificity, affinity, and ability, are the residues from the recipient's complementarity determining region (CDR) have the desired specificity, affinity, and ability It includes human immunoglobulin (recipient antibody) substituted with (donor antibody). In some instances, Fv framework residues of human immunoglobulin are replaced by corresponding non-human residues. Humanized antibodies may also comprise residues which are not found in the recipient antibody or in the imported CDR or framework sequences. In general, a humanized antibody comprises substantially all of at least one, typically two, variable domains, all or substantially all of the CDR regions correspond to CDRs of non-human immunoglobulin, all or substantially Indeed, all FR regions are those of human immunoglobulin consensus sequences. The humanized antibody optionally also comprises at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin (Jones et al., Nature 321: 522-525). (1986); Riechmann et al., Nature, 332: 323-329 (1988); and Presta, Curr. Op. Struct. Biol., 2: 593-596 (1992)).

  Methods for humanizing non-human antibodies are well known in the art. In general, humanized antibodies have one or more amino acid residues transferred to an antibody from a source that is non-human. These non-human amino acid residues are often referred to as import residues, which are typically taken from an import variable domain. Humanization is essentially determined according to Winter and co-workers [Jones et al. , Nature, 321: 522-525 (1986); Riechmann et al. , Nature 332: 323-327 (1988); Verhoeyen et al. Chem., 239: 1534-1536 (1988)] by substituting the corresponding sequences of human antibodies for rodent CDRs or CDR sequences. Accordingly, such humanized antibodies are chimeric antibodies (US Pat. No. 4,186,567), wherein substantially less than an intact human variable domain has been substituted by the corresponding sequence from a non-human species. In practice, humanized antibodies are typically human antibodies in which some CDR residues and possibly some FR residues are substituted by residues from analogous sites in rodent antibodies .

  Human antibodies can be prepared by various techniques known in the art (phage display library (Hoogenboom and Winter, J. Mol. Biol., 227: 381 (1991); Marks et al., J. Mol. Biol., 222: 581 (1991)) can also be used. Cole et al. and Boerner et al. Techniques are also available for the preparation of human monoclonal antibodies (Cole et al., Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, p. 77 (1985) and Boerner et al., J. Immunol., 147 (1 ): 86-95 (1991)). Similarly, human antibodies can be made by transfer of human immunoglobulin loci into transgenic animals (eg, mice in which the endogenous immunoglobulin genes have been partially or completely inactivated). During the challenge, production of human antibodies is observed which closely resembles in all respects the properties observed in humans, including gene rearrangement, assembly and antibody repertoire. This approach is described, for example, in U.S. Patent Nos. 5,545,807; 5,545,806; 5,569,825; 5,625,126; 5,633,425. No. 5,661,016, and the following scientific publications: Marks et al. , Bio / Technology 10: 779-783 (1992); Lonberg et al. Nature 368: 856-859 (1994); Morrison, Nature 368 812-13 (1994); Fishwild et al. , Nature Biotechnology 14, 845-51 (1996); Neuberger, Nature Biotechnology 14: 826 (1996); and Lonberg and Huszar, Intern. Rev. Immunol. 13, 65-93 (1995).

  Preferably, the antibody of this aspect of the invention specifically binds at least one epitope of a polypeptide variant of the invention. As used herein, the term "epitope" refers to any antigenic determinant on an antigen to which the paratope of an antibody binds.

  Epitopic determinants usually consist of chemically active surface groupings of molecules such as amino acids or carbohydrate side chains and usually have specific three dimensional structural characteristics and specific charge characteristics.

  Optionally, creating unique epitopes in the variants by alteration of one or more post-translational modifications (including but not limited to glycosylation and / or phosphorylation) as described below Can. Such changes can also generate new epitopes, for example by removal of glycosylation at specific sites.

  The epitope of the present invention is also optionally contiguous with at least one other portion of the variant, which is contiguous with the unique sequence portion in the linear polypeptide itself but can still be combined to form the epitope. It may comprise some or all of the unique sequence parts of the variants of the invention in combination. One or more unique sequence parts, optionally, one or more other discrete parts of the variant (including parts that may have high homology with parts of known proteins) The epitopes can be formed in combination.

Immunoassays In another embodiment of the invention, immunoassays can be used to qualitatively or quantitatively detect and analyze markers in a sample. The method comprises the steps of providing an antibody that specifically binds to the marker, contacting the sample with the antibody, and detecting the presence of a complex of the antibody bound to the marker in the sample.

  Purified protein markers can be used to prepare antibodies that specifically bind the markers. Antibodies that specifically bind to protein markers can be prepared using any suitable method known in the art.

  After preparing the antibodies, the markers can be detected and / or quantified using a number of well-recognized immunological binding assays. Useful assays include, for example, enzyme immunoassay (EIA) (such as enzyme linked immunosorbent assay (ELISA)), radioimmunoassay (RIA), western blot assay, or slot blot assay (eg, US Pat. Nos. 4,366,241; 4,376,110; 4,517,288; and 4,837,168). In general, a sample obtained from a subject can be contacted with an antibody that specifically binds the marker.

  Optionally, the antibody can be immobilized on a solid support prior to contacting the antibody with the sample to facilitate linear and subsequent isolation of the complex. Examples of solid supports include, but are not limited to, glass or plastic in the form of, for example, microtiter plates, sticks, beads, or microbeads. The antibodies can also be attached to a solid support.

  After incubation of the sample with the antibody, the mixture can be washed and the antibody-marker complex formed can be detected. This can be done by incubation of the wash mixture with the detection reagent. Alternatively, a direct assay that detects markers in the sample, eg, bound marker-specific antibodies using a second labeled antibody, and / or a mixture of monoclonal antibodies that bind, for example, different epitopes of the marker It can be detected using co-incubated competition or inhibition assays.

  Throughout the assay, incubation and / or washing steps may be required after each combination of reagents. The incubation step may vary from about 5 seconds to several hours, preferably from about 5 minutes to about 24 hours. However, the incubation time depends on the assay format, markers, volume of solution, concentration and so on. Typically, the assay is performed at ambient temperature, but can be performed in a range such as 10 ° C to 40 ° C.

  Immunoassays can be used to determine the marker test amount in a sample from a subject. First, markers of the test amount in a sample can be detected using the immunoassay method described above. If a marker is present in the sample, and the marker is present in the sample, the marker forms an antibody-marker complex with an antibody that specifically binds the marker under the appropriate incubation conditions described above. Optionally, the amount of antibody-marker complex can be determined by comparison to a standard. As mentioned above, it is not necessary to measure the test amount of marker in absolute units, as long as the unit of measurement can be compared to the control amount and / or signal.

  It is preferred to use an antibody that specifically interacts with the polypeptide of the invention but does not, for example, interact with wild-type protein or other isoforms. Such antibodies are directed, for example, to the unique sequence portions of the polypeptide variants of the invention, including but not limited to the crosslinks, tips, tails, and insertions described in more detail below. . Preferred embodiments of the antibodies of the invention are described in more detail in the section "Antibodies".

Radioimmunoassay (RIA): In one version, this method involves precipitation of the desired substrate, specific antibodies and radiolabeled antibody binding proteins immobilized on a precipitable carrier such as agarose beads in the method detailed below (Eg, Protein A labeled with ¹²⁵ ). The number of sedimented pellets is proportional to the base mass.

  Another version of RIA uses labeled substrate and unlabeled antibody binding protein. Samples containing unknown amounts of substrate are added in various amounts. The reduction in the number of precipitates of labeled substrate is proportional to the amount of substrate in the added sample.

  Enzyme-Linked Immunosorbent Assay (ELISA): This method involves the immobilization of a sample (eg, immobilized cells or protein solution) containing a protein substrate to a surface, such as a well of a microtiter plate. A substrate specific antibody coupled to the enzyme is applied and allowed to bind to the substrate. The presence of the antibody is then detected and quantified by colorimetric reaction using an enzyme coupled to the antibody. Enzymes commonly used in this method include horseradish peroxidase and alkaline phosphatase. When well calibrated and within the linear reaction range, the amount of substrate present in the sample is proportional to the amount of color developed. Substrate standards are generally used to improve quantitative accuracy.

  Western Blot: This method involves the separation of the substrate from the other proteins by acrylamide gel and the subsequent transfer of the substrate to a membrane (eg nylon or PVDF). The presence of the substrate is then detected by an antibody specific for the substrate and then bound by an antibody binding reagent. The antibody binding reagent can be, for example, protein A or another antibody. The antibody binding reagent can be radioactively labeled or conjugated to an enzyme as described above. It can be detected by autoradiography, colorimetric reagents, or chemiluminescence. The substrate can be quantified by this method and its identity can be determined by the relative position of the membrane, which indicates the migration distance in the acrylamide gel during electrophoresis.

  Immunohistochemical analysis: This method involves the detection of substrate in situ in fixed cells by substrate specific antibodies. Substrate specific antibodies can be conjugated to an enzyme or to a fluorophore. Detect by microscopy and subjective assessment. When using enzyme linked antibodies, a colorimetric reaction may be required.

  Fluorescence activated cell sorting (FACS): This method involves detection of substrate in situ in cells by substrate specific antibodies. Substrate specific antibodies are detected by a cell sorting device which reads the wavelength of light emitted from each cell as it passes from the light beam. This method can use two or more antibodies simultaneously.

Radio Imaging Methods These methods include, but are not limited to, positron emission tomography (PET), single photon emission computed tomography (SPECT). Both these techniques are non-invasive and can be used to detect and / or measure a wide variety of tissue events and / or functions (eg, detection of cancer cells, etc.). Unlike PET, SPECT can optionally be used simultaneously with two labels. SPECT likewise has several other advantages, for example, in terms of cost and type of label that can be used. For example, U.S. Patent No. 6,696,686 describes the use of SPECT for breast cancer detection, as this patent is fully described herein. It is incorporated as a reference.

Display Library According to yet another aspect of the invention, at least 6, at least 7, at least 8, at least 9, at least 10, at least 10-15, each from the polypeptide sequence of the invention Display library comprising a plurality of display vehicles (such as phage, viruses or bacteria) displaying at least 12-17, at least 15-20, at least 15-30, or at least 20-50 contiguous amino acids I will provide a.

  Methods for constructing such display libraries are well known in the art. Such methods are described, for example, in Young AC, et al. "The three-dimensional structures of a polysaccharide binding antibody to Cryptococcus neoformans and its complex with a peptide from a phage display library: implications for the identification of peptide mimotopes" J Mol Biol 1997 Dec 12; 274 (4): 622-34 Giebel LB et al. Davies EL et al., "Biochemistry 1995 Nov 28; 34 (47): 15430-5; Davies EL et al.," Determination of cyclic peptide phage libraries with identity identities that bind streptavidin with high affinity ". J. Immunol Methods 1995 Oct 12; 186 (1): 125-35; Jones C RT al., "Selection of specific phage-displaying antibodies using libraries derived from chicken immunoglobin genes". "Current trends in molecular recognition and bioseparation" J Chromatogr A 1995 Jul 14; 707 (1): 3-22; Deng SJ et al. Proc Natl Acad Sci USA 1995 May 23; 92 (11): 4992-6; and Deng SJ et al. "Basis for selection of improved carbohydrate-binding single-chain antibodies from synthetic gene libraries". "Selection of antibody single-chain variable fragments with improved carbohydrate binding by phage display" J Biol Chem 1994 Apr. 1; 269 (13): 9533-8, which is incorporated herein by reference.

  The following sections relate to examples of candidate markers (section 1) and experimental data for examples of these markers (section 2).

Example of Candidate Markers Section This section relates to examples of sequences of the present invention, including exemplary selection methods thereof.

Description of the method taken to reveal the biomolecule of the present invention Human EST and cDNA, GenBank version 136 (ftp. Ncbi. Nih. Gov / genbank / release. Notes / gb136. Release June 15, 2003 April 2003 NCBI genome assembly; June 2003 RefSeq sequence; Genbank version 139 (December 2003); NCBI human genome (Build 34) (from October 2003); And from the LifeSeq library of the Incyte Corporation (EST only; Wilmington, DE, USA). For GenBank sequences, human EST sequences from the EST (GBEST) section and human mRNA sequences from the primate (GBPRI) section were used, and a human nucleotide RefSeq mRNA sequence was also used (eg www.ncbi.nlm.nih) .Gov / Genbank / GenbankOverview.html and references in the section EST (see www.ncbi.nlm.nih.gov/dbEST/); general references (dbuski) for dbEST (EST database in GenBank) et al, Nat Genet. 1993 Aug; 4 (4): 332-3), which is incorporated herein by reference as if fully described herein. See))

  Novel splice variants are described by Sorek, R. et al. , Ast, G., et al. & Graur, D. Alu-containing exons are alternatively spliced. Genome Res 12, 1060-7 (2002); US Patent No. 6,625, 545; US Patent Application No. 10/426, 002, published May 27, 2004 as US 20040101876 (all of which are incorporated herein by reference. The prediction was made using the LEADS clustering and assembly system as described herein) as if fully described therein. Briefly, software removes expression sequences from repeats, vectors, and immunoglobulins. The software then aligns the expressed sequence with a cluster that overlaps the expressed sequence into genomes and genes or "clusters" representing partial genes that allow for alternative splicing.

  These were annotated using the GeneCarta (Compugen, Tel-Aviv, Israel) platform. GeneCarta platform has rich annotation pool, sequence information (especially spliced sequences), chromosomal information, alignment, and additional information (SNP, gene ontology terms, expression profile, functional analysis, detailed domain structure, known and presumed Including proteins and detailed homology reports).

  The candidate selection method will be briefly described. However, it should be noted that this description is given for the purpose of description only and is in no way intended to limit the present invention. Potential markers were identified by computational processes designed to find overexpressed genes and / or their splice variants in tumor tissue by using databases of expressed sequences. Various parameters related to the information in the EST library determined according to the manual classification process were used to aid in the localization of overexpressed genes and / or their splice variants in cancerous tissue. A detailed description of the selection method is given in Example 1 below. A summary of the cancer marker selection engine and the following wet validation step summary is shown in FIG.

Example 1: Identification of differentially expressed gene products-Algorithm In order to distinguish between differentially expressed gene products and constitutively expressed genes (ie, housekeeping genes), an algorithm based on frequency analysis was set up. Specific algorithms for the identification of transcripts overexpressed in cancer are described below.

Dry analysis
Library Annotation-EST library is manually classified according to the following.
-Tissue origin-Biological source-Examples of biological sources frequently used for construction of EST libraries include cancer cell lines, normal tissues, cancer tissues, fetal tissues, and others (normal cell lines, Normal cell line pools, cancer cell lines, and combinations thereof). Specific descriptions of the abbreviations used below for these tissues / cell lines are given above.
Library Construction Protocol-Various methods are known in the library construction art and include standardized library construction, non-standardized library construction, subtraction library, ORESTES, etc. It is occasionally recognized that the library construction protocol is not indicated.

  Follow the rules below.

  The EST library from the same biological sample is considered as one library.

  The EST library contaminated at the above average levels (eg, DNA contamination etc.) was excluded. The presence of such contamination was determined as follows. For each library, non-splicing ESTs that were not completely contained within other splicing sequences were counted. The ratio of such sequences (compared to other sequences) will tag the library as a contamination if it is at least 4 standard deviations higher than the average of the whole library analyzed and excluded from further consideration in the following analysis (See also Sorek, R. & Safer, H. M. A. novel algorithm for computational identification of contaminated EST libraries. Nucleic Acids Res 31, 1067-74 (2003) for further details).

  Clusters (genes) with at least 5 sequences (including at least 2 sequences from the tissue of interest) were analyzed. As mentioned above, splice variants were identified by use of the LEADS software package.

Example 2: Identification of Overexpressed Genes in Cancer Two different scoring algorithms were developed.

  Library score-Candidate sequences supported by multiple cancer libraries are more likely to function as specific and effective diagnostic markers.

  Basic Algorithm-For each cluster, the contributing sequences of cancer library and normal library to cluster were counted. Fisher's exact test was used to check if the cancer library was significantly over-expressed in clusters compared to the total number of cancer library and normal library.

  Library Counting: Small libraries (e.g. less than 1000 sequences) were excluded from consideration unless involved in a cluster. For this reason, the total number of libraries is actually adjusted for each cluster.

  Clone number score-Generally, EST numbers are much higher in cancer libraries compared to normal libraries, which may indicate actual overexpression.

Algorithm-
Clone Counting: For the counting of EST clones, each library protocol class was weighted as follows based on our belief that the protocol reflects the actual expression level.
(I) Denormalization: 1
(Ii) Normalization: 0.2
(Iii) All other classes: 0.1

  Clone number score-The total number of weighted EST clones from the cancer library was compared to EST clones from normal library. In order to avoid one library contributing to multiple scores, the library contribution given to the most libraries of a given cluster was limited to 2 clones.

（式中、ｃ−クラスター中の「癌」クローンの重み付けした数、
Ｃ−全「癌」ライブラリー中のクローンの重み付けした数、
ｎ−クラスター中の「正常」クローンの重み付けした数、
Ｎ−全「正常」ライブラリー中のクローンの重み付けした数
）として計算した。 Score,

Where the weighted number of "cancer" clones in the c-cluster,
C-weighted number of clones in the whole "cancer" library,
Weighted number of "normal" clones in n-cluster,
Calculated as N-weighted number of clones in all "normal" libraries.

  Clone number score significance-Significantly over-expressed in a cluster of EST clones from cancer library compared to the total number of EST clones from cancer library and normal library using Fisher's exact test I checked if I would like to.

The following two search approaches were used to find either general cancer-specific or tumor-specific candidates.
• Count libraries / sequences from tumor tissue as well as libraries from cancer cell lines ("normal" cell lines were ignored).
Count only libraries / sequences from tumor tissue.

Example 3 Identification of Tissue Specific Genes For detection of tissue specific clusters, the tissue library / sequence was compared to the total number of libraries / sequences in the cluster. Similar statistical tools as above were used to identify tissue specific genes. The tissue abbreviation is identical to the cancer tissue but is shown with the heading "normal tissue".

  Algorithm-For each test tissue T and each test cluster, the following was tested:

1. Each cluster contains at least two libraries from tissue T. 1. at least three clones from tissue T in the cluster (weighted as above), and Tissue T derived clones are at least 40% of all clones involved in the test cluster.

  To check that the numbers are statistically significant, the Fisher's exact test P value was calculated for both the library and the weighted clones.

Example 4: Identification of Splice Variants Overexpressed in Cancer of Clusters Not Overexpressed in Cancer A cancer specific splice variant comprising a unique region was identified.

Identification of Unique Sequence Regions in Splice Variants Regions are defined as adjacent exons that always or do not appear together in each splice variant.

  A "segment" (sometimes referred to as a "seg" or "node") is defined as the shortest adjacent transcription region that does not contain known splicing inside.

Only reliable ESTs were considered for analysis of regions and segments. EST was defined as unreliable if:
(I) non-splicing,
(Ii) not targeted by RNA;
(Iii) not targeted by spliced ESTs, and (iv) alignment with the proximal end portion of the long poly A stretch or the proximal start of the long poly T stretch.

Trusted regions were selected for further scoring. Unique sequence regions were considered to be reliable if:
(I) alignment with the genome, and (ii) a region favored over 2 ESTs.

Algorithm The transcript set is divided into two groups according to each unique sequence region:
(I) Transcripts including this region (TA group)
(Ii) Transcripts not including this region (TB group)

The EST clone sets of each cluster are divided into the following three groups.
(I) those that support (derived from) transcripts of group TA (S1).
(Ii) those that support transcripts of group TB (S2).
(Iii) Supporting transcripts from both groups (S3).

  The above library and clone number scores were given to the S1 group.

  Using the Fisher's exact test P value, whether S1 is significantly enriched by cancer EST clones compared to S2, and S1 compared to cluster background (S1 + S2 + S3) It was checked whether it enriched significantly.

  Thus, the identification of unique sequence regions and the segmentation of transcripts are shown in FIG. Each of these unique array regions correspond to segments, also called "nodes".

  Region 1: common to all transcripts, so no mutations are considered to be detected; region 2: specific for transcript 1; region 3: specific for transcripts 2 and 3, region 4: transcript Specific for 3, region 5: specific for transcripts 1 and 2, region 6: specific for transcript 1.

Example 5 Identification of Cancer-Specific Splice Variants of Genes Expressed Excise and Depression in Cancer Search for the EST Support (No mRNA) Region of the Following Genes:
(I) Known cancer markers (ii) Genes shown to be overexpressed in cancer in published microarray experiments.

A reliable EST support region was defined as supported by at least one of the following:
(I) Three splicing ESTs
(Ii) 2 spliced ESTs from 2 libraries,
(Iii) 10 non-splicing ESTs from 2 libraries, or (iv) 3 libraries.

Actual Marker Examples The following examples relate to specific actual marker examples.

EXPERIMENTAL TERMS This section relates to the examples describing experiments including these sequences as well as exemplary non-limiting methods, assays, and examples of their use. Materials and experimental procedures are described first, as they were used as a basis for the studies carried out in all experiments.

  The markers of the invention were tested for their expression in various cancerous and non-cancerous tissue samples. The samples used in the panel are described in Table 2 below. The samples used in the normal tissue panel are described in Table 3 below. The test was then conducted as described in the "Materials and Experimental Procedures" section below.

Materials and Experimental Procedures Preparation of RNA-RNA was obtained from Clontech (Franklin Lakes, NJ USA 07417, www.clontech.com), BioChain Inst. Inc. (Hayward, CA 94545 USA www.biochain.com), ABS (Wilmington, DE 1980, USA, http://www.absbioreagents.com), or Ambion (Austin, TX 78744 USA, http: //www.ambion. com). Alternatively, RNA was generated from tissue samples using TRI reagent (Molecular Research Center) according to the manufacturer's instructions. Tissue and RNA samples were obtained after patient or death. Total RNA samples were treated with DNase I (Ambion) and purified using RNeasy columns (Qiagen).

  RT-PCR-purified RNA (1 μg) was mixed with 150 ng Random Hexamer primer (Invitrogen) and 500 μM dNTPs in a total volume of 15.6 μl. The mixture was incubated at 65 ° C. for 5 minutes and chilled on ice. Then 5 μl of 5 × Superscritp II first strand buffer (Invitrogen), 2.4 μl of 0.1 M DTT, and 40 units of RNasin (Promega) are added and the mixture is incubated for 10 minutes at 25 ° C., then Further incubation at 42 ° C. for 2 minutes. Then, 1 μl (200 units) of Superscritp II (Invitrogen) was added and the reaction (final volume 25 μl) was incubated for 50 minutes at 42 ° C. and then for 15 minutes at 70 ° C. The cDNA obtained was diluted 20 fold with TE buffer (10 mM Tris (pH = 8), 1 mM EDTA (pH = 8)).

Real-time RT-PCR analysis-cDNA (5 μl) prepared as described above was prepared using SYBR Green I assay (PE Applied Biosystems) using specific primers and UNG enzyme (Eurogentech, ABI or Roche) Used as template in time PCR reaction. Amplification was performed as follows: 2 minutes at 50 ° C., 10 minutes at 95 ° C., then 40 cycles of 15 seconds at 95 ° C., then 1 minute at 60 ° C. Detection was performed by use of PE Applied Biosystems SDS7000. The cycle at which the reaction achieved the threshold level of fluorescence (Ct) was recorded and used to calculate the relative transcript level in the RT reaction. The relative amount was calculated using the formula: Q = efficiency ^{^ -Ct} . PCR reaction efficiency was calculated from a standard curve generated by use of serial dilutions of several reverse transcription (RT) reactions. To minimize intrinsic differences in RT responses, the relative amounts obtained were normalized to the geometric mean of the relative amounts of several housekeeping (HSKP) genes. A summary of the quantitative real-time PCR analysis summary is shown in FIG. As shown, the x-axis indicates the number of cycles. C _T = threshold cycle point (the cycle at which the amplification curve crosses the experimentally set fluorescence threshold). This point is the calculated number of cycles where the signal of the PCR product is above the background level (passive dye ROX) but still in the geometric / logarithmic phase. (As shown, once the fluorescence level crosses the measurement threshold, there is a geometric growth phase, the measurement between which is the most accurate, and then the linear phase and plateau phase; Because the latter two phases are not accurately measured). The y-axis shows normalized reporter fluorescence. It should be noted that this analysis type performs relative quantification.

The sequence of the housekeeping gene determined in all the examples in the test panel was:
Ubiquitin (GenBank Accession No. BC000449)
Ubiquitin forward primer (SEQ ID NO: 326): ATTTGGGTCGCGGTTCTTG
Ubiquitin reverse primer (SEQ ID NO: 327): TGCCTTGACATTCTCGATGGT
Ubiquitin-Amplicon (SEQ ID NO: 328)
ATTTGGGTCGCGGTTCTTGTTTGTGATCGTCTGTGATCGTC ACTTGACAATGCAGATCTTCGTGAGAGCTCTGACTGGTAAGACCATC ACCCTCGAGG TTGAGCCCAGTGACACACCGAGAATGTCAAGGCA

SDHA (GenBank accession number NM_004168)
SDHA forward primer (SEQ ID NO: 329): TGGGAACAAGAGGGCATCTG
SDHA reverse primer (SEQ ID NO: 330): CCACCACTGCATCAAATTCATG
SDHA-Amplicon (SEQ ID NO: 331): TGGGAACAAGAGGGCATCTGCTAAAGTTTCAGATTCCATTTCTGCTCGATCATCCAGTAGTGGATCATGAATTTGATGCAGTGGTGG

PBGD (GenBank accession number BC019323),
PBGD forward primer (SEQ ID NO: 332): TGAGAGTGATTCGCGTGGG
PBGD reverse primer (SEQ ID NO: 333): CCAGGGTACGAGGCTTTCAAT
PBGD-Amplicon (SEQ ID NO: 334): TGAGTGTGATTCGCGTGGGTACCCCGAAGACGAGCAGCTTGCTC GCATACAGACGGACAGTGTGGGCAACATTGAAAGCCTCGTACCCTGG

HPRT1 (GenBank accession number NM_000194),
HPRT1 forward primer (SEQ ID NO: 1295): TGACACTGGCAAAACAATGCA
HPRT1 reverse primer (SEQ ID NO: 1296): GGTCCTTTTCACCAGCAAGCT
HPRT1- amplicon (SEQ ID NO: 1297): TGACACTGGCAAACAATGCAGACTTTGCTTTCCTTGGTCAGGCAGTATAATCAAAGATGGTCAAGGTCGCAAGCTTGCTGATGAAAAGGACC

The sequence of the housekeeping gene measured in all the examples in normal tissue samples was:

RPL 19 (GenBank accession number NM_000981),
RPL 19 forward primer (SEQ ID NO: 1298): TGGCAAGAAGAAGGTCTGGTTAG
RPL19 reverse primer (SEQ ID NO: 1420): TGATCAGCCCATCTTTGATGAG
RPL19 – amplicon (SEQ ID NO: 1630): TGGCAAGAAGAAGGTCTGGTTAGACCCCAATGAGACCAATGAAATGCCCAATGCAACTACTCCGTCAGCAGATCCGGAAGCTCATCAAAGATGGGCTGATCA
TATA box (GenBank accession number NM_003194),
TATA box forward primer (SEQ ID NO: 1631): CGGTTTGCTGCGGTAATCAT
TATA box reverse primer (SEQ ID NO: 1632): TTTCTTGCTGCCAGTCTGGAC
TATA box – amplicon (SEQ ID NO: 1633): CGGTTTGCTGCGGTAATCATGAGGATAAGAGAGCCACGAACACAGCGAC ACTGATTTTCAGTTC TGGGAAAATGGTGTGCACAGGAGCCAAGAGTGAAGAACAAGTCCAGACTGGCAAGCAAAAA
Ubiquitin (GenBank Accession No. BC000449)
Ubiquitin forward primer (SEQ ID NO: 326): ATTTGGGTCGCGGTTCTTG
Ubiquitin reverse primer (SEQ ID NO: 327): TGCCTTGACATTCTCGATGGT
Ubiquitin-Amplicon (SEQ ID NO: 328)
ATTTGGGTCGCGGTTCTTGTTTGTGATCGTCTGTGATCGTC ACTTGACAATGCAGATCTTCGTGAGAGCTCTGACTGGTAAGACCATC ACCCTCGAGG TTGAGCCCAGTGACACACCGAGAATGTCAAGGCA
SDHA (GenBank accession number NM_004168)
SDHA forward primer (SEQ ID NO: 329): TGGGAACAAGAGGGCATCTG
SDHA reverse primer (SEQ ID NO: 330): CCACCACTGCATCAAATTCATG
SDHA-Amplicon (SEQ ID NO: 331): TGGGAACAAGAGGGCATCTGCTAAAGTTTCAGATTCCATTTCTGCTCGATCATCCAGTAGTGGATCATGAATTTGATGCAGTGGTGG

Oligonucleotide-Based Microarray Experiment Protocol Microarray Construction Microarrays (chips) were printed by pin deposition using a MicroGrid II MGII 600 robot from Bio Robotics Limited (Cambridge, UK). A. Shoshan et al, "Optical technologies and informatics", Proceedings of SPIE. Vol 4266, pp. A 50-mer oligonucleotide target sequence was designed by Compugen Ltd (Tel-Aviv, IL) as described in 86-95 (2001). The designed oligonucleotides are synthesized and purified by desalting using the Sigma-Genosys system (The Woodlands, TX, US), and all oligonucleotides are linked at the 5 'end to a C6 amino modified linker or CodeLink slide (Cat # 25-6700-01 Amersham Bioscience, Piscataway, NJ, US) directly attached. The 50-mer oligonucleotides forming the target sequence were first suspended in Ultra-pure DDW (Cat # 01-866-1A Kibbutz Beit-Haemek, Israel) to a concentration of 50 μM. Before printing on slides, the oligonucleotides were resuspended in 300 mM sodium phosphate (pH 8.5) to a final concentration of 150 mM and printed at 21-40C, 35-40% relative humidity.

  Each slide contained a total of 9792 features in 32 subarrays. The 4224 features were the target sequence and negative control of the present invention printed two by two. An additional 288 features (96 target sequences printed in triplicate) contained the housekeeping gene from Human Evaluation Library 2, Compugen Ltd, Israel. Another 384 features are E. coli spikes 1 to 6, which are oligos of E. coli genes that are commercially available at Array Control product (Array control-sense oligo spots, Ambion Inc. Austin, TX, Cat # 1781, Lot # 112 K06). It is.

Post-Coupling of the Printed Slides After spotting the oligonucleotides onto a processing glass (CodeLink) slide, the slides were incubated for 24 hours in a sealed NaCl humid chamber (70-75% relative humidity).

  Slides are incubated for 15 minutes in 50 ° C. blocking solution (0.1 M Tris, 50 mM ethanolamine, 10 ml buffer containing 0.1% SDS) for blocking the remaining reactive groups. It was processed. The slides were then rinsed twice with Ultra-pure DDW (double distilled water). The slides were then washed on a shaker for 30 minutes with a 50 ° C. wash (10 ml / slide, 4 × SSC, 0.1% SDS). The slides were then rinsed twice with Ultra-pure DDW and dried by centrifugation at 800 rpm for 3 minutes.

  The slides were then treated with VentanaDiscovery hybridization station barcode adhesive to aid in the automation of the hybridization protocol. The printed slides were loaded onto a Bio-Optica (Milan, Italy) hematology staining device and incubated in 50 ml of 3-aminopropyltriethoxysilane (Sigma A3648 lot # 122K589) for 10 minutes. Excess liquid was allowed to dry and slides were incubated for 3 hours in a 20 mm / Hg dark vacuum desiccator (Pelco 2251, Ted Pella, Inc. Redding CA).

  In order to conduct microarray experiments, the following protocol was followed using Genisphere 900-RP (Random Primer) using mini-elution column on Ventana Discovery HybStation < Briefly, the protocol was performed as described for the instructions and information provided by the device itself. The protocol included cDNA synthesis and labeling. cDNA concentrations were measured using TBS-380 (Turner Biosystems. Sunnyvale, CA.) PicoFlour used with OliGreen ssDNA quantitation reagent and kit.

  Hybridization was performed using a Ventana hybridization device according to the provided protocol (Discovery Hybridization Station Tuscon AZ).

  The slides were then scanned using Axon Instruments Inc's GenePix 4000B dual laser scanner and analyzed by GenePix Pro 5.0 software.

  A summary of the oligonucleotide-based microarray fabrication and experimental flow summary is shown in FIGS. 4 and 5.

  Briefly, as shown in FIG. 4, 15 μM DNA oligonucleotides were deposited (printed) on Amersham'CodeLink 'glass slides to create well-contoured “spots”. These slides are coated with a survey hydrophobic polymer chemistry to create an active three-dimensional surface covalently attached to the 5 'end of the DNA oligonucleotide via C6-amine modification. This conjugation ensures that full-length DNA oligonucleotides are available for hybridization with cDNA and that lower background, high sensitivity, and reproducibility are also obtained.

  FIG. 5 shows how to perform a microarray experiment. It should be noted that the left and right stages can optionally be performed in any order (including parallel) up to stage 4 (hybridization). Briefly, on the left side, target oligonucleotides are spotted onto glass slides for microscopy (optionally other materials can be used) to form spotting slides (stage 1). On the right, control and cancer sample RNAs are Cy3 and Cy5 labeled (stage 2), respectively, to form labeled probes. It should be noted that control and cancer samples are derived from corresponding tissues (eg, normal prostate tissue and cancerous prostate tissue). In addition, the tissues from which the RNA was taken are shown below as specific examples of data for particular clusters for overexpression of oligonucleotides from the "chip" (microarray) (eg cancerous prostate tissue and normal tissue "Prostate" for tips tested as in At stage 3, the probes are mixed. At stage 4, hybridization is performed to form a processed slide. At stage 5, the slides were washed and scanned to create an image file, and then data was analyzed at stage 6.

The following clusters were found to be overexpressed in lung cancer.
W60282_PEA_1
F05068_PEA_1
H38804_PEA_1
HSENA 78
T39971
(R00299)
H14624
Z41644_PEA_1
Z25299_PEA_2
HSSTROL3
HUMTREFAC_PEA_2
HSS 100 PCB
HSU33147_PEA_1
HUMCA1 XIA
H61775
HUMGRP5E
HUMODCA
AA 161 187
R66178
D56406_PEA_1
M85491_PEA_1
Z21368_PEA_1
HUMCA1 XIA
R20779
R38144_PEA_2
Z44808_PEA_1
HUMOSTRO_PEA_1_PEA_1
R11723_PEA_3
AI076020
T23580
M79217_PEA_1
M62096_PEA_1
M78076_PEA_1
T99080_PEA_4
T08446_PEA_1
R16276_PEA_1

The following clusters were found to be overexpressed in small cell lung cancer.

H61775
HUMGRP5E
M85491_PEA_1
Z44808_PEA_1
AA 161 187
R66178
HUMPHOSLIP_PEA_2

AI076020
T23580
M79217_PEA_1
M62096_PEA_1
M78076_PEA_1
T99080_PEA_4
T08446_PEA_1

The following clusters were found to be overexpressed in lung adenocarcinoma.
R00299
M85491_PEA_1
Z21368_PEA_1
HUMCA1 XIA
AA 161 187
R66178
T11628_PEA_1

The following clusters were found to be overexpressed in lung squamous cells.
HUMODCA
R00299
D56406_PEA_1
Z44808_PEA_1
Z21368_PEA_1
HUMCA1 XIA
AA 161 187
R66178
HUMCEA_PEA_1
R35137_PEA_1_PEA_1_PEA_1

Description of Cluster H61775 Cluster H61775 features 2 transcripts and 6 segments of interest, the names of which are shown in Tables 4 and 5 respectively, and the sequence itself is shown at the end of the application. Selected protein variants are shown in Table 6.

  Cluster H61775 can be used as a diagnostic marker by overexpression of transcripts of this cluster in cancer. The expression of such transcripts in normal tissues is also shown by the method previously described. The terms "numbers" in the right column of the table and the numbers on the y-axis of FIG. 6 refer to the weighted expression of ESTs in each category as "ppm" (the ppm of ESTs of a particular cluster in this category by ppm Ratio of expression to expression of all ESTs).

  In general, as shown for the histograms in FIG. 6 and Table 7, the following results were obtained. This cluster was overexpressed (at least at minimal levels) in the following pathological conditions: a mixture of brain malignant brain tumors and malignant tumors from different tissues.

  As mentioned above, Contig H61775 features the two transcripts shown in Table 3 above. A description of each mutein of the present invention is given here.

  The mutein H61775_P16 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript H61775_T21. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison of H61775_P16 and Q9P2J2 (SEQ ID NO: 1694). Corresponding to the amino acids 11 to 93 of Q9P2J2 and to the amino acids 1 to 83 of H61775_P16, corresponding to the 1st amino acid sequence of H61775_P16, and to the UT At least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous Of and a amino acid sequence, wherein the first and second amino acid distribution is contiguous, and in sequential order, the isolated chimeric polypeptide coding H61775_P16.

  2. H61775_P16 comprising a sequence of at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence An isolated polypeptide encoding a tail.

Report on comparison of H61775_P16 with AAQ88495 (SEQ ID NO: 1695) A corresponding amino acid 1 to 83 of AAQ 88495 and a corresponding amino acid 1 to 83 of H61775_P16 are also used as the first amino acid sequence of H61775_P16 and the corresponding amino acid 84 to 15 At least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous And a second amino acid sequence, wherein the first and second amino acid distribution is contiguous, and in sequential order, the isolated chimeric polypeptide coding H61775_P16.

  2. H61775_P16 comprising a sequence of at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The mutein is considered to be positioned as follows with respect to secretory cells. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein H61775_P16 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing the other amino acids, and listing the other amino acids, as shown in Table 9; It indicates whether it is known and the presence of a known SNP in the mutein H61775_P16 sequence supports the deduced sequence of this mutein of the invention).

  The mutein H61775_P16 is encoded by the following transcript: H61775_T21 (sequences shown at the end of the application). The coding portion of the transcript H61775_T21 is shown in bold, starting from position 261 and ending at position 716. The transcript also has the following SNPs listed in Table 10 (showing its position on the nucleotide acid sequence, listing another nucleic acid, the last column indicating whether the SNP is known, a mutein The presence of a known SNP in the H61775_P16 sequence supports the deduced sequence of this mutein of the invention).

  The mutein H61775_P17 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript H61775_T22. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between H61775_P17 and Q9P2J2 An isolated chimeric polypeptide encoding H61775_P17 comprising the first amino acid sequence which is at least 90% homologous to MVWCLGLAVLSLVISSQGADGRGKPEV VSV VGRAGE SV VL GC DLL PHA GRP PLH VIEW LR FGFL LPI FIF IQ FG PRISP I, corresponding to amino acids 11 to 93 of Q9 P2 J2.

Report of comparison between H61775_P17 and AAQ88495 1. An isolated chimeric polypeptide encoding H61775_P17 comprising the first amino acid sequence which is at least 90% homologous to MVWCLGLAVLSLVISSQGADGRGKPEV VSV VGRAGE SV VLGCDLLPPA GRPPLHVIEW LRGFGLIPIF IQFGLYSPRIDVY corresponding to amino acids 1 to 83 of AAQ 88495 and corresponding to H61775 P17 amino acids 1 to 83.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The mutein is considered to be positioned as follows with respect to secretory cells. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein H61775_P17 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing the other amino acids, and listing the other amino acids, as shown in Table 11 It indicates whether it is known and the presence of a known SNP in the mutein H61775_P17 sequence supports the deduced sequence of this mutein of the invention).

  The mutein H61775_P17 is encoded by the following transcript: H61775_T22 (sequences shown at the end of the application). The coding portion of the transcript H61775_T22 is shown in bold, starting from position 261 and ending at position 509. The transcript also has the following SNPs listed in Table 12 (showing its position on the nucleotide acid sequence, listing another nucleic acid, the last column shows if the SNP is known, the mutein The presence of known SNPs in the H61775_P17 sequence supports the deduced sequence of this mutant protein of the invention).

  As mentioned above, cluster H61775 features the six segments listed in Table 4 above, the sequences of which are shown at the end of the application. These segments are part of the nucleic acid sequence, which are of particular interest and are individually described herein. A description of each segment of the invention is provided herein.

  The segment cluster H61775_node_2 of the present invention is supported by 17 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: H61775_T21 and H61775_T22. Table 13 below describes the start and end positions of this segment on each transcript.

  The segment cluster H61775_node_4 of the present invention is supported by 20 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: H61775_T21 and H61775_T22. Table 14 below describes the start and end positions of this segment on each transcript.

The segment cluster H61775_node_6 of the present invention is supported by one library. The number of libraries was determined as described above. This segment can be found in the following transcript: H61775_T22. Table 15 below describes the start and end positions of this segment on each transcript.

  The segment cluster H61775_node_8 of the present invention is supported by five libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: H61775_T21. Table 16 below describes the start and end positions of this segment on each transcript.

  According to an optional embodiment of the present invention, there is also provided a short segment associated with the above cluster. These segments are up to about 120 bp in length and are therefore included in the individual descriptions.

  The segment cluster H61775_node_0 of the present invention is supported by four libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: H61775_T21 and H61775_T22. Table 17 below describes the start and end positions of this segment on each transcript.

  The segment cluster H61775_node_5 of the invention can be found in the following transcript: H61775_T22. Table 18 below describes the start and end positions of this segment on each transcript.

  Microarray (chip) data of this gene is also available, as follows. As described above, with respect to the clusters themselves, different oligonucleotides were tested for differential expression in different disease states, in particular cancer. The following oligonucleotides were found to reach this segment (for lung cancer) (shown in Table 19).

Mutated protein alignment against previously known proteins:
Sequence name: / tmp / Psw0RJLCti / aLAXQjXh07: Q9P2J2

Sequence documentation:

Alignment of: H61775_P16 x Q9P2J2 ..

Alignment segment 1/1:

Quality: 803.00 Escore: 0
Matching length: 83 Total length: 83
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MVWCLGLLSLVISSQGADGRGKPEV VSV VGRAGESVVLGCDLLPPAGRP 50
||||||||||||||||||||||||||||||||||||||||
11 MVWCLLAVLSLVISQGADGRGPPEV VSV VGRAGESVVLGCDLLPPAGRP 60
....
51 PLHVIEWLRFGFLLPIFIFFGLYSPRIDPDYVG 83
||||||||||||||||||||||||||||||
61 PLHVIEWLRFGFLLPIFIQFGLYSPRIDPDYVG 93






Sequence name: / tmp / Psw0RJLCti / aLAXQjXh07: AAQ88495

Sequence documentation:

Alignment of: H61775_P16 x AAQ88495 ..

Alignment segment 1/1:

Quality: 803.00 Escore: 0
Matching length: 83 Total length: 83
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MVWCLGLLSLVISSQGADGRGKPEV VSV VGRAGESVVLGCDLLPPAGRP 50
||||||||||||||||||||||||||||||||||||||||
1 MVWCLGLLSLVISSQGADGRGKPEV VSV VGRAGESVVLGCDLLPPAGRP 50
....
51 PLHVIEWLRFGFLLPIFIFFGLYSPRIDPDYVG 83
||||||||||||||||||||||||||||||
51 PLHVIEWLRFGFLLPIFIFFGLYSPRIDPDYVG 83






Sequence name: / tmp / naab8yR3GC / pSM4l2IL5o: Q9P2J2

Sequence documentation:

Alignment of: H61775_P17 x Q9P2J2 ..

Alignment segment 1/1:

Quality: 803.00 Escore: 0
Matching length: 83 Total length: 83
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MVWCLGLLSLVISSQGADGRGKPEV VSV VGRAGESVVLGCDLLPPAGRP 50
||||||||||||||||||||||||||||||||||||||||
11 MVWCLLAVLSLVISQGADGRGPPEV VSV VGRAGESVVLGCDLLPPAGRP 60
....
51 PLHVIEWLRFGFLLPIFIFFGLYSPRIDPDYVG 83
||||||||||||||||||||||||||||||
61 PLHVIEWLRFGFLLPIFIQFGLYSPRIDPDYVG 93






Sequence name: / tmp / naab8yR3GC / pSM4l2IL5o: AAQ88495

Sequence documentation:

Alignment of: H61775_P17 x AAQ88495 ..

Alignment segment 1/1:

Quality: 803.00 Escore: 0
Matching length: 83 Total length: 83
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MVWCLGLLSLVISSQGADGRGKPEV VSV VGRAGESVVLGCDLLPPAGRP 50
||||||||||||||||||||||||||||||||||||||||
1 MVWCLGLLSLVISSQGADGRGKPEV VSV VGRAGESVVLGCDLLPPAGRP 50
....
51 PLHVIEWLRFGFLLPIFIFFGLYSPRIDPDYVG 83
||||||||||||||||||||||||||||||
51 PLHVIEWLRFGFLLPIFIFFGLYSPRIDPDYVG 83

Expression of H61775 transcript of immunoglobulin superfamily member 9 detectable by an amplicon as shown in sequence name H61775seg8 in normal and cancerous lung tissue seg8, H61775 seg8 amplicon (SEQ ID NO: 1636), and H61775 seg8 F2 (SEQ ID NO: 1634) And transcripts of immunoglobulin superfamily member 9 detectable by H61775seg8R2 (SEQ ID NO: 1635) primers were measured by real-time PCR. In parallel, four housekeeping genes – PBGD (GenBank accession number BC019232, amplicon – PBGD-amplicon (SEQ ID NO: 334), primers SEQ ID NO: 332 and 333), HPRT1 (GenBank accession) Session No. NM — 000194, Amplicon – HPRT 1-Amplicon (SEQ ID NO: 1297), Primers SEQ ID Nos. 1295 and 1296), Ubiquitin (GenBank Accession No. BC000449, Amplicon – Ubiquitin-Amplicon (SEQ ID No) 328), SEQ ID NO: 326 and 327) of the primers, and SDHA (GenBank Accession No. NM_004168, amplicon – SDHA-Amplicon (SEQ ID NO: 331) Was measured similarly primers SEQ ID NO: 329 and 330). For each RT sample, the expression of the amplicon was normalized to the geometric mean of the housekeeping gene dose. The normalized volume of each RT sample is the median volume of normal postmortem (PM) samples (sample numbers 47-50, 90-93, 96-99, Table 2, "tissue samples in the test panel") Divided to obtain the magnification of upregulation of each sample relative to the median of normal PM samples.

  FIG. 7 is a histogram showing over expression of the above immunoglobulin superfamily member 9 in cancerous lung samples compared to normal samples. The numbers and proportions of samples showing at least 5 times overexpression of the total number of samples tested are shown below.

  As apparent from FIG. 7, the expression of immunoglobulin superfamily member 9 transcripts detectable by the above amplicon in a cancer sample is a non-cancerous sample (sample numbers 47-50, 90-93, 96-99, It was significantly higher than Table 2, "Tissue samples in test panel". Obviously, 11 out of 15 adenocarcinoma samples, 12 out of 16 squamous cell carcinoma samples, 1 out of 4 large cell carcinoma samples, 8 out of 8 small cell carcinoma samples Over expression of at least 5 fold was found.

  Statistical analysis was applied to verify the significance of these results as described below.

  The P value for the difference in expression levels of immunoglobulin superfamily member 9 transcripts detectable by the amplicon in lung cancer samples versus normal tissue samples was determined by T-test to be 6.5E-02. For adenocarcinoma, the minimum was 7.62 E-03 for squamous cell carcinoma and 1.5 E-03 for small cell carcinoma.

  The 5-fold overexpression threshold was found to be different between cancer and normal samples, P value is 9.62E-04 for adenocarcinoma, 5.9E-04 for squamous cell carcinoma, 10 The threshold for fold overexpression was found to differ between small cell carcinoma and normal samples, checked by Fisher's exact test, and the P value was 7.14E-05. The above values indicate that the results are statistically significant.

  Primer pairs are also optionally and preferably included within the scope of the present invention, for example, in the above experiments the following primers were used only as non-limiting examples of suitable primer pairs: H61775seg8F2 forward primer and H61775seg8R2 reverse Direction primer.

  The present invention also preferably includes any amplicon obtained by use of any suitable primer pair (e.g. in the above experiments) and obtained the following amplicons only as a non-limiting illustration of a suitable amplicon : H61775seg8.

H61775 seg 8 F 2 (SEQ ID NO: 1634)
GAAGGCTCTTGTCACTTACTAGCCAT
H61775seg8R2 (SEQ ID NO: 1635)
TGTCACCATATTTAATCCTCCCAA
H61775 seg 8 (SEQ ID NO: 1636)
GAAGGCTCTTGTCACTTACTAGCCATGTGTATTATGAGTAGAAACTTAACTAATTAATTCAATTCAGCTACAATGGAATTCTTGGGAGGATTAATATATGGTGACA

Expression of the H61775 Transcript of Immunoglobulin Superfamily Member 9 Detectable by the Amplicon Shown in the Sequence Name H61775seg8 in Different Normal Tissues H61775seg8 amplicon (SEQ ID NO: 1636), H61775 seg8F2 (SEQ ID NO: 1634), and H61775seg8R2 (SEQ ID NO: 1 Transcripts of immunoglobulin superfamily member 9 detectable by 1635) were measured by real-time PCR. In parallel, four housekeeping genes-RPL19 (GenBank Accession No. NM_000981, RPL19 amplicon (SEQ ID No. 1630)), TATA box (GenBank Accession No. NM_003194, TATA amplicon (SEQ ID No. 1633)), ubiquitin (GenBank Access No. Session number BC000449; amplicon – ubiquitin amplicon (SEQ ID NO: 328), and SDHA (GenBank accession number NM_004168; amplicon – SDHA amplicon (SEQ ID NO: 331)) similarly measured did. For each RT sample, the expression of the amplicon was normalized to the geometric mean of the housekeeping gene dose. The normalized amount of each RT sample is divided by the median of the amount of ovary samples (Sample Nos. 18-20, Table 4, "Tissue samples in normal panel") to obtain relative expression values of each sample relative to ovary samples Obtained.

H61775 seg 8 F 2 (SEQ ID NO: 1634)
GAAGGCTCTTGTCACTTACTAGCCAT
H61775seg8R2 (SEQ ID NO: 1635)
TGTCACCATATTTAATCCTCCCAA
H61775 seg 8 (SEQ ID NO: 1636)
GAAGGCTCTTGTCACTTACTAGCCATGTGTATTATGAGTAGAAACTTAACTAATTAATTCAATTCAGCTACAATGGAATTCTTGGGAGGATTAATATATGGTGACA

  The results are shown in FIG. 8, which shows the expression of the H61775 transcript of immunoglobulin superfamily member 9 detectable by the amplicon shown in the sequence name H61775seg8 in different normal tissues.

Description of Cluster M85491 Cluster M85491 features 2 transcripts of interest and 11 segments, the names of which are shown in Tables 20 and 21 respectively, and the sequence itself is shown at the end of the application. Selected protein variants are shown in Table 22.

  These sequences are known from the known protein Ephrin type B receptor 2 (precursor), previously referred to herein as protein (SwissProt accession identifier EPB2_HUMAN, synonym EC 2.7.1.112, tyrosine-protein) A variant of the kinase receptor EPH-3, DRT, receptor protein-tyrosine kinase HEK5, also known as ERK) (SEQ ID NO: 1417).

  The protein Ephrin type B receptor 2 (precursor) is known or is considered to have the following functions: receptor of the ephrin-B family member. The sequence of the protein Ephrin type B receptor 2 (precursor) is shown at the end of the application as "protein Ephrin type B receptor 2 (precursor) amino acid sequence" (SEQ ID NO: 1417). Known polymorphisms of this sequence are shown in Table 23.

  The localized protein Ephrin type B receptor 2 (precursor) is considered to be a type I membrane protein.

  The following GO annotation applies to previously known proteins. The following annotations have been found: protein amino acid phosphorylation which is an annotation related to biological processes, transmembrane receptor protein tyrosine kinase signaling pathway, a protein which is an annotation related to neurogenesis, molecular function Endogenous membrane proteins that are annotations related to tyrosine kinases, receptors, transmembrane ephrin receptors, ATP binding, transferases, and cellular components.

  GO assignments can be made at one or more http: // www. expasy. SwissProt / TremBl Protein knowledgebase available from ch / sprot / or http: // www. ncbi. nlm. nih. Depends on Locuslink available from gov / projects / LocusLink /.

  Cluster M85491 can be used as a diagnostic marker by overexpression of transcripts of this cluster in cancer. The expression of such transcripts in normal tissues is also shown by the method previously described. The terms "numbers" in the right column of the table and the numbers on the y-axis of FIG. 9 refer to the weighted expression of ESTs in each category as "ppm" (the ppm of ESTs of a particular cluster in this category by ppm Ratio of expression to expression of all ESTs).

  In general, as shown for the histograms in FIG. 9 and Table 24, the following results were obtained. This cluster was overexpressed (at least at minimal levels) in the following pathological conditions: a mixture of epithelial malignant brain tumors and malignant tumors from different tissues.

  As mentioned above, cluster M85491 is characterized by the two transcripts listed in Table 20 above. These transcripts encode proteins which are variants of the protein Ephrin type B receptor 2 (precursor). A description of each variant of the invention is provided herein.

  The mutein M85491_PEA_1_P13 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript M85491_PEA_1_T16. An alignment to a known protein (Ephrin type B receptor 2 (precursor)) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report on comparison between M85491_PEA_1_P13 and EPB2_HUMAN 1. Corresponding to amino acids 1 to 476 of EPB2_HUMAN, corresponding to amino acids 1 to 476 of M85491_PEA_1_P13 MALRRLGAALLLLPLLAAVEETLMDSTTATAELGWMVHPPSGWEEVSGYDENMNTIRTYQVCNVFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCSSIPSVPGSCKETFNLYYYEADFDSATKTFPNWMENPWVKVDTIAADESFSQVDLGGRVMKINTEVRSFGPVSRSGFYLAFQDYGGCMSLIAVRVFYRKCPRIIQNGAIFQETLSGAESTSLVAARGSCIANAEEVDVPIKLYCNGDGEWLVPIGRCMCKAGFEAVENGTVCRGCPSGT A first amino acid sequence at least 90% homologous to KeieienukyujidiieishitieichishiPiaienuesuarutitiesuijieitienushibuishiaruenujiwaiwaiarueidierudiPierudiemuPishititiaiPiesueiPikyueibuiaiesuesubuienuitiesueruemueruidaburyutiPiPiarudiesujijiaruidierubuiwaienuaiaishikeiesushijiesujiarujieishitiarushijidienubuikyuwaieiPiarukyuerujierutiiPiaruaiwaiaiesudieruerueieichitikyuwaitiefuiaikyueibuienujibuitidikyuesuPiefuesuPikyuefueiesubuienuaititienukyueieiPiesueibuiesuaiemueichikyubuiesuarutibuidiesuITLSWSQPDQPNGVILDYELQYYEK, polypeptide at least 70% with a sequence corresponding to VPIGWVLSPSPTSLRAPLPG to amino acid 477-496 of M85491_PEA_1_P13, optionally at least 80%, preferably at least 85%, more Preferably An isolated chimeric poly encoding M85491_PEA_1_P13, comprising a second amino acid sequence which is at least 90%, most preferably at least 95% homologous, said first and second amino acid sequences being in a contiguous and sequential order peptide.

  2. M85491_PEA_1_P13 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence VPIGWVLSPSPTSLRAPLPG in M85491_PEA_1_P13 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The mutein is considered to be positioned as follows with respect to secretory cells. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein M85491_PEA_1_P13 is encoded by the following transcript: M85491_PEA_1_T16 (sequences shown at the end of the application). The code portion of transcript M85491_PEA_1_T16 is shown in bold, this code portion starting at position 143 and ending at position 1630. The transcript also has the following SNPs listed in Table 26 (showing its position on the nucleotide acid sequence, listing another nucleic acid, and the last column indicating if the SNP is known, a mutein The presence of known SNPs in the M85491_PEA_1_P13 sequence supports the deduced sequence of this mutein of the invention).

  The mutein M85491_PEA_1_P14 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript M85491_PEA_1_T20. An alignment to a known protein (Ephrin type B receptor 2 (precursor)) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report on comparison between M85491_PEA_1_P14 and EPB2_HUMAN 1. Corresponding to amino acids 1 to 270 of EPB2_HUMAN, at least the corresponding MALRRLGAALLLLPLLAAVEETLMDSTTATAELGWMVHPPSGWEEVSGYDENMNTIRTYQVCNVFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCSSIPSVPGSCKETFNLYYYEADFDSATKTFPNWMENPWVKVDTIAADESFSQVDLGGRVMKINTEVRSFGPVSRSGFYLAFQDYGGCMSLIAVRVFYRKCPRIIQNGAIFQETLSGAESTSLVAARGSCIANAEEVDVPIKLYCNGDGEWLVPIGRCMCKAGFEAVENGTVCR to amino acid 1 to 270 of M85491_PEA_1_P14 A polypeptide having a first amino acid sequence of 0% homology and the sequence ERQDLTMLSRLVLSNSWPQMILPPPQPPKVLEL corresponding to amino acids 271 to 301 of M85491_PEA_1_P14, at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90 An isolated chimeric polypeptide encoding M85491_PEA_1_P14, comprising a second amino acid sequence that is%, most preferably at least 95% homologous, said first and second amino acid sequences being adjacent and in sequential order.

  2. M85491_PEA_1_P14 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence ERQDLTLSRLVLNSWPQMILPPPLPKVLEL in M85491_PEA_1_P14 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The mutein is considered to be positioned as follows with respect to secretory cells. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein M85491_PEA_1_P14 is encoded by the following transcript: M85491_PEA_1_T20 (sequences shown at the end of the application). The code portion of transcript M85491_PEA_1_T20 is shown in bold, this code portion starting at position 143 and ending at position 1045. The transcript also has the following SNPs listed in Table 27 (showing its position on the nucleotide acid sequence, listing another nucleic acid, and the last column indicating if the SNP is known, a mutein The presence of known SNPs in the M85491_PEA_1_P14 sequence supports the deduced sequence of this mutein of the invention).

  As mentioned above, cluster M85491 is characterized by the eleven segments listed in Table 21 above, the sequence of which is shown at the end of the application. These segments are part of the nucleic acid sequence, which are of particular interest and are individually described herein. A description of each segment of the invention is provided herein.

  The segment cluster M85491_PEA_1_node_0 of the present invention is supported by 5 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: M85491_PEA_1_T16 and M85491_PEA_1_T20. Table 28 below describes the start and end positions of this segment on each transcript.

  The segment cluster M85491_PEA_1_node_13 of the present invention is supported by six libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: M85491_PEA_1_T20. Table 29 below describes the start and end positions of this segment on each transcript.

  The segment cluster M85491_PEA_1_node_21 of the present invention is supported by 18 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: M85491_PEA_1_T16. Table 30 below describes the start and end positions of this segment on each transcript.

  The segment cluster M85491_PEA_1_node_23 of the present invention is supported by 18 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: M85491_PEA_1_T16. Table 31 below describes the start and end positions of this segment on each transcript.

  The segment cluster M85491_PEA_1_node_24 of the present invention is supported by three libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: M85491_PEA_1_T16. Table 32 below describes the start and end positions of this segment on each transcript.

  The segment cluster M85491_PEA_1_node_8 of the present invention is supported by 25 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: M85491_PEA_1_T16 and M85491_PEA_1_T20. Table 33 below describes the start and end positions of this segment on each transcript.

  Microarray (chip) data for this segment is also available, as follows. As described above, with respect to the clusters themselves, different oligonucleotides were tested for differential expression in different disease states, in particular cancer. The following oligonucleotides were found to reach this segment (for lung cancer) (shown in Table 34).

  The segment cluster M85491_PEA_1_node_9 of the present invention is supported by 20 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: M85491_PEA_1_T16 and M85491_PEA_1_T20. Table 35 below describes the start and end positions of this segment on each transcript.

  According to an optional embodiment of the present invention, there is also provided a short segment associated with the above cluster. These segments are up to about 120 bp in length and are therefore included in the individual descriptions.

  The segment cluster M85491_PEA_1_node_10 of the present invention is supported by 17 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: M85491_PEA_1_T16 and M85491_PEA_1_T20. Table 36 below describes the start and end positions of this segment on each transcript.

  The segment cluster M85491_PEA_1_node_18 of the present invention is supported by 15 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: M85491_PEA_1_T16. Table 37 below describes the start and end positions of this segment on each transcript.

  The segment cluster M85491_PEA_1_node_19 of the present invention is supported by 15 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: M85491_PEA_1_T16. Table 38 below describes the start and end positions of this segment on each transcript.

  The segment cluster M85491_PEA_1_node_6 of the present invention is supported by 11 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: M85491_PEA_1_T16 and M85491_PEA_1_T20. Table 39 below lists the start and end positions of this segment on each transcript.

Mutated protein alignment against previously known proteins:
Sequence name: / tmp / qfmsU9VtxS / DylcLC9j8v: EPB2_HUMAN

Sequence documentation:

Alignment of: M85491_PEA_1_P13 x EPB2_HUMAN ..

Alignment segment 1/1:

Quality: 4726.00 Escore: 0
Matching length: 476 Total length: 476
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MALRRLGAALLLLPLLAVAEETLMDSTTATAELGWMHPPSGWEEVSGYD 50
||||||||||||||||||||||||||||||||||||||||
1 MALRRLGAALLLLPLLAVAEETLMDSTTATAELGWMHPPSGWEEVSGYD 50
....
51 ENMNTIRTYQ VCNVFFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCSSI 100
||||||||||||||||||||||||||||||||||||||||
51 ENMNTIRTYQ VCNVFFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCSSI 100
....
101 PSVPGSCKETFNLYYYEAFD FSAT KTTFPNWMENPWVKVDTIAADESFSQV 150
||||||||||||||||||||||||||||||||||||||||
101 PSVPGSCKETFNLYYYEAFD FSAT KTTFPNWMENPWVKVDTIAADESFSQV 150
....
151 DLGGRVMKINTEVRSFGPVSSRGYLAFQDYGGCMSLIAVRVFYRKCPRI 200
||||||||||||||||||||||||||||||||||||||||
151 DLGGRVMKINTEVRSFGPVSSRGYLAFQDYGGCMSLIAVRVFYRKCPRI 200
....
201 IQNGAIFQETLSGAESTSLVAARGSCIANAEEVDVPIKLYCNGDGEWLVP 250
||||||||||||||||||||||||||||||||||||||||
201 IQNGAIFQETLSGAESTSLVAARGSCIANAEEVDVPIKLYCNGDGEWLVP 250
....
251 IGRCMCKAGFEAVENGTVCRGCPSGTFKANQGDEACTHCPINSRTTSEGA 300
||||||||||||||||||||||||||||||||||||||||
251 IGRCMCKAGFEAVENGTVCRGCPSGTFKANQGDEACTHCPINSRTTSEGA 300
....
301 TNCVCRNGYYRADLDPLDMPPCTTIPSAPQAVISSVNETSLLEWTPPRDS 350
||||||||||||||||||||||||||||||||||||||||
301 TNCVCRNGYYRADLDPLDMPPCTTIPSAPQAVISSVNETSLLEWTPPRDS 350
....
351 GGREDLVYNIICKSCGSGRGACTRCGDNVQYAPRQLGLTEPRIYISDLLA 400
||||||||||||||||||||||||||||||||||||||||
351 GGREDLVYNIICKSCGSGRGACTRCGDNVQYAPRQLGLTEPRIYISDLLA 400
....
401 HTQYTFEIQAVNGVTDQSPSPQFASVNITTNQAAPSAVSIMHQVSRTVD 450
||||||||||||||||||||||||||||||||||||||||
401 HTQYTFEIQAVNGVTDQSPSPQFASVNITTNQAAPSAVSIMHQVSRTVD 450
.
451 SITLSWSQPDQPNGL VIDYELQYYEK 476
||||||||||||||||||||||||
451 SITLSWSQPDQPNGL VIDYELQYYEK 476






Sequence name: / tmp / rmnzuDbot6 / GiHbjeU8iR: EPB2_HUMAN

Sequence documentation:

Alignment of: M85491_PEA_1_P14 x EPB2_HUMAN ..

Alignment segment 1/1:

Quality: 2673.00 Escore: 0
Matching length: 270 Total length: 270
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MALRRLGAALLLLPLLAVAEETLMDSTTATAELGWMHPPSGWEEVSGYD 50
||||||||||||||||||||||||||||||||||||||||
1 MALRRLGAALLLLPLLAVAEETLMDSTTATAELGWMHPPSGWEEVSGYD 50
....
51 ENMNTIRTYQ VCNVFFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCSSI 100
||||||||||||||||||||||||||||||||||||||||
51 ENMNTIRTYQ VCNVFFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCSSI 100
....
101 PSVPGSCKETFNLYYYEAFD FSAT KTTFPNWMENPWVKVDTIAADESFSQV 150
||||||||||||||||||||||||||||||||||||||||
101 PSVPGSCKETFNLYYYEAFD FSAT KTTFPNWMENPWVKVDTIAADESFSQV 150
....
151 DLGGRVMKINTEVRSFGPVSSRGYLAFQDYGGCMSLIAVRVFYRKCPRI 200
||||||||||||||||||||||||||||||||||||||||
151 DLGGRVMKINTEVRSFGPVSSRGYLAFQDYGGCMSLIAVRVFYRKCPRI 200
....
201 IQNGAIFQETLSGAESTSLVAARGSCIANAEEVDVPIKLYCNGDGEWLVP 250
||||||||||||||||||||||||||||||||||||||||
201 IQNGAIFQETLSGAESTSLVAARGSCIANAEEVDVPIKLYCNGDGEWLVP 250
.
251 IGRCMCKAGFEAVENGTVCR 270
|||||||||||||||||||
251 IGRCMCKAGFEAVENGTVCR 270

Ephrin type-B receptor 2 precursor (EC 2.7. 1. 112) (tyrosine-protein kinase receptor EPH-3) M8549 transcript detectable by an amplicon as shown in sequence name M 85491 seg 24 in normal and cancerous lung tissue Ephrin type-B receptor 2 precursor (EC 2.7.1.112) detectable by primers seg24, M85491 seg24 amplicon (SEQ ID NO: 1639), M85491 seg 24 F (SEQ ID NO: 1637), and M85491 seg 24 R (SEQ ID NO: 1638) The expression of tyrosine-protein kinase receptor EPH-3) transcripts was measured by real-time PCR. In parallel, four housekeeping genes-PBGD (GenBank Accession No. BC019323, Amplicon – PBGD-Amplicon, SEQ ID No. 334), HPRT1 (GenBank Accession No. NM_000194, Amplicon – HPRT1- Amplicons, SEQ ID NO: 1297), Ubiquitin (GenBank Accession No. BC000449, Amplicon – Ubiquitin-Amplicon SEQ ID NO: 328), and SDHA (GenBank Accession No. NM_004168, Amplicon – SDHA-Amplicon SEQ ID NO: 331) was similarly measured. For each RT sample, the expression of the amplicon was normalized to the geometric mean of the housekeeping gene dose. The normalized volume of each RT sample is the median volume of normal postmortem (PM) samples (sample numbers 47-50, 90-93, 96-99, Table 2, "tissue samples in the test panel") Divided to obtain the magnification of upregulation of each sample relative to the median of normal PM samples.

   FIG. 10 below shows the excess of the above-described Ephrin type-B receptor 2 precursor (EC 2.7.1.112) (tyrosine-protein kinase receptor EPH-3) transcript in cancerous lung samples compared to normal samples. It is a histogram which shows expression. Values represent the average of duplicate experiments. Error bars indicate the obtained minimum and maximum values. The numbers and proportions of samples showing at least 3 times overexpression of the total number of samples tested are shown below.

  As apparent from FIG. 10, the expression of Ephrin type-B receptor 2 precursor (EC 2.7. 1. 112) (tyrosine-protein kinase receptor EPH-3) transcript detectable by the above amplicon cancer sample is , Non-cancerous samples (sample numbers 47-50, 90-93, 96-99, Table 2, "tissue samples in test panel") were significantly higher. Clearly, at least 3-fold overexpression was found in 9 out of 15 adenocarcinoma samples and 4 out of 8 small cell carcinoma samples.

  Statistical analysis was applied to verify the significance of these results, as described below.

  The 3-fold overexpression threshold was found to be different between cancer and normal samples, and when checked by Fisher's exact test, the P value is 7.42E-03 in adenocarcinoma, small cell carcinoma It was 5.69E-02. The above values indicate that the results are statistically significant.

  Primer pairs are also optionally and preferably included within the scope of the present invention, for example, in the above experiments the following primers were used only as non-limiting examples of suitable primer pairs: M85491 seg24F forward primer and M85491 seg24 R reverse Direction primer.

  The present invention also preferably includes any amplicon obtained by use of any suitable primer pair (e.g. in the above experiments) and obtained the following amplicons only as a non-limiting illustration of a suitable amplicon : M85491 seg 24.

M85491 seg 24 F (SEQ ID NO: 1637)-GGCGTCTTTTCTCCCCTGAAC
M85491 seg 24 R (SEQ ID NO: 1638)-GTCCCATTCTGGGTGCTGTG
M85491 seg 24 (SEQ ID NO: 1639) > GGCGTTCTTTCTCCTCTCCAACTCCAGTTTCCACCTGTGTGAGTGTGGGTGAGACCCCTCGCGGGGAGCTATGCAGGTTACGGAAGAAAGGCAGCAGCACCCAGAATGGCAC

Expression of Ephrin type-B receptor 2 precursor (EC 2.7.1.112) (tyrosine-protein kinase receptor EPH-3) M8549 transcript detectable by an amplicon shown in the sequence name M85491 seg24 in different normal tissues The expression of Ephrin type-B receptor 2 precursor transcripts detectable by amplicons (SEQ ID NO: 1639), M85491seg24F (SEQ ID NO: 1637), and M85491seg24R (SEQ ID NO: 1638) was measured by real-time PCR. In parallel, four housekeeping genes-RPL19 (GenBank Accession No. NM_000981, RPL19 amplicon, SEQ ID No. 1630), TATA box (GenBank Accession No. NM_003194, TATA amplicon, SEQ ID No. 1633), ubiquitin (GenBank Accession No. BC000449, amplicon – ubiquitin amplicon, SEQ ID NO: 328), and SDHA (GenBank accession number NM_004168; amplicon >#8211; SDHA-amplicon, SEQ ID NO: 331) were similarly measured. For each RT sample, the expression of the amplicon was normalized to the geometric mean of the housekeeping gene dose. The relative expression of each sample relative to the lung sample divided by the median of the amounts of lung samples (Sample Nos. 15-17 above, Table 2, "Tissue Samples in Normal Panel") above each RT sample I got a value.

M85491 seg 24 F (SEQ ID NO: 1637)-GGCGTCTTTTCTCCCCTGAAC
M85491 seg 24 R (SEQ ID NO: 1638)-GTCCCATTCTGGGTGCTGTG
M85491 seg 24 (SEQ ID NO: 1639) > GGCGTTCTTTCTCCTCTCCAACTCCAGTTTCCACCTGTGTGAGTGTGGGTGAGACCCCTCGCGGGGAGCTATGCAGGTTACGGAAGAAAGGCAGCAGCACCCAGAATGGCAC

  The results shown in FIG. 11 are the expression of Ephrin type-B receptor 2 precursor (tyrosine-protein kinase receptor EPH-3) M85491 transcript detectable by an amplicon as shown in the sequence name M85491 seg24 in different normal tissues Indicates

Description of Cluster T39971 Cluster T39971 is characterized by 4 transcripts of interest and 28 segments, the names of which are shown in Tables 40 and 41, respectively, and the sequences themselves are shown at the end of the application. Selected protein variants are shown in Table 42.

  These sequences are known proteins Vitronectin precursor (SwissProt accession identifier VTNC_HUMAN, synonym serum nucleic acid factor; S-protein; also known as V75), which is a known protein previously referred to herein as a protein It is a variant of SEQ ID NO: 1418).

  The protein vitronectin precursor is known or considered to have the following functions: Vitronectin is a cell adhesion and nucleic acid factor found in serum and tissues. Vitronectin interacts with glycosaminoglycans and proteoglycans. It is recognized by certain members of the integrin family and serves as a cell-substrate adhesion molecule. Inhibitors of the membrane damaging effects of the distal cytolytic complement pathway. The sequence of the protein vitronectin precursor is shown at the end of the application as "vitronectin precursor amino acid sequence". Known polymorphisms of this sequence are shown in Table 4.

  Localization of the protein vitronectin precursor is considered extracellular.

  The previously known proteins also have the following indications and / or potential therapeutic applications: cancer, melanoma. Clinical / therapeutic applications in humans (e.g. as targets for antibodies or small molecules and / or as direct therapy) are being investigated and available information related to these investigations is: Potential pharmaceutically relevant or therapeutically relevant activities of previously known proteins are: αβ3 integrin antagonists, apoptosis agonists. The therapeutic role of proteins displayed by clusters is expected. Because information is present in drug databases or public databases (eg, above) that may or may not be used to apply this protein or a portion thereof to a potential treatment (anti-cancer drug), the clusters Assigned to this area.

  The following GO annotation applies to previously known proteins. The following annotations were found: immune responses related to biological processes, immune responses, cell adhesion, protein binding related to molecular function, protein binding, heparin binding, and annotations related to cellular components Extracellular space.

  GO assignments can be made at one or more http: // www. expasy. SwissProt / TremBl Protein knowledgebase available from ch / sprot / or http: // www. ncbi. nlm. nih. Depends on Locuslink available from gov / projects / LocusLink /.

  Cluster T39971 can be used as a diagnostic marker by overexpression of transcripts of this cluster in cancer. The expression of such transcripts in normal tissues is also shown by the method previously described. The terms "numbers" in the right column of the table and the numbers on the y-axis of FIG. 12 refer to the weighted expression of ESTs in each category as "ppm" (the ppm of ESTs of a particular cluster in this category by ppm Ratio of expression to expression of all ESTs).

  As shown generally for the histograms in FIG. 12 and Table 44, the following results were obtained. This cluster was overexpressed (at least at minimal levels) in the following pathological conditions: liver cancer, lung malignancy, and pancreatic cancer.

  As mentioned above, cluster T39971 is characterized by the four transcripts listed in Table 40 above. These transcripts encode a protein that is a mutated form of vitronectin precursor. A description of each mutein of the invention is provided herein.

  The mutein T39971_P6 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript T39971_T5. An alignment to a known protein (vitronectin precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between T39971_P6 and VTNC_HUMAN 1. Corresponding to amino acids 1-276 of VTNC_HUMAN, at least a MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAECKPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGVLDPDYPRNISDGFDGIPDNVDAALALPAHSYSGRERVYFFKG corresponding to amino acids 1-276 of T39971_P6 9 % And a polypeptide having the sequence TQGVVGD corresponding to amino acids 277 to 283 of T39971_P6 and at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% An isolated chimeric polypeptide encoding T39971_P6, most preferably comprising a second amino acid sequence which is at least 95% homologous, said first and second amino acid sequences being adjacent and in sequential order.

  2. T39971_P6 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence TQGVVGD in T39971_P6 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The mutein is considered to be positioned as follows with respect to secretory cells. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein T39971_P6 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows SNPs as shown in Table 46) It is shown whether it is known and the presence of a known SNP in the mutein T39971_P6 sequence supports the deduced sequence of this mutein of the invention).

  The mutein T39971_P6 is encoded by the following transcript: T39971_T5 (sequences shown at the end of the application). The coding portion of the transcript T39971_T5 is shown in bold, starting from position 756 and ending at position 1604. The transcript also has the following SNPs listed in Table 47 (showing its position on the nucleotide acid sequence, listing another nucleic acid, and the last column indicating if the SNP is known, a mutein The presence of known SNPs in the T39971_P6 sequence supports the deduced sequence of this mutant protein of the invention).

  The mutein T39971_P9 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript T39971_T10. An alignment to a known protein (vitronectin precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between T39971_P9 and VTNC_HUMAN 1. Corresponding to amino acids 1 to 325 of VTNC_HUMAN, corresponding to amino acids 1 to 325 of T39971_P9 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAECKPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGVLDPDYPRNISDGFDGIPDNVDAALALPAHSYSGRERVYFFKGKQYWEYQ SQQHQPSQ EEC GEL S 2 90 90 90 90 90 SG SG SG 399 399 399 399 399 399 399 399 399 399 399 399 399 399 399 399 399 399 399 399 399 399 399 399. An isolated chimeric polypeptide encoding T39971_P9, wherein said first and second amino acid sequences are in contiguous and sequential order.

  2. Length “n” (wherein n is at least about 10 amino acids long, optionally at least about 20 amino acids long, preferably at least about 30 amino acids long, more preferably at least about 40 amino acids long, most preferably at least about 50 amino acids long, at least two amino acids comprising TS, starting from any of the following structures: amino acid numbers 325-x to 325, amino acid numbers 326 + ((n-2) -x) (formula An isolated chimeric polypeptide encoding the edge portion of T39971_P9, comprising a polypeptide, having a sequence terminating in: x) varying from 0 to n-2).

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The mutein is considered to be positioned as follows with respect to secretory cells. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein T39971_P9 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows SNPs as shown in Table 48) It is shown whether it is known and the presence of a known SNP in the mutein T39971_P9 sequence supports the deduced sequence of this mutein of the invention).

  The mutein T39971_P9 is encoded by the following transcript: T39971_T10 (sequences shown at the end of the application). The coding portion of transcript T39971_T10 is shown in bold and this coding portion starts at position 756 and ends at position 2096. The transcript also has the following SNPs listed in Table 49 (showing its position on the nucleotide acid sequence, listing another nucleic acid, and the last column indicating if the SNP is known, a mutein The presence of known SNPs in the T39971_P9 sequence supports the deduced sequence of this mutant protein of the invention).

  The mutein T39971_P11 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript T39971_T12. An alignment to a known protein (vitronectin precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between T39971_P11 and VTNC_HUMAN 1. Corresponding to amino acids 1 to 326 of VTNC_HUMAN, corresponding to amino acids 1 to 326 of T39971_P11 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAECKPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGVLDPDYPRNISDGFDGIPDNVDAALALPAHSYSGRERVYFFKGKQYWEY A first amino acid sequence which is at least 90% homologous to FQHQPSQEECEGSSLSAVFEHFAM MQRDWEDIF WGRTS, and DKYYRVNLRTRRVDTVTVDPPYPRSIAQYWLGCPAPGHL corresponding to amino acids 442-478 of VTNC_HUMAN, and also to amino acids 323-363 of T39971_P11 An isolated chimeric polypeptide encoding T39971_P11, wherein said first and second amino acid sequences are in contiguous and sequential order.

  2. Length “n” (wherein n is at least about 10 amino acids long, optionally at least about 20 amino acids long, preferably at least about 30 amino acids long, more preferably at least about 40 amino acids long, most preferably at least about 50 amino acids long, at least two amino acids comprising SD, starting from any of the following structures: amino acids nos. 326-x to 326, amino acids nos. 327 + ((n-2)-x) (formula An isolated chimeric polypeptide encoding the edge portion of T39971_P11, comprising a polypeptide, having a sequence terminating in:

Report of the comparison between T39971_P11 and Q9BSH7 (SEQ ID NO: 1696) Corresponding to amino acids 1 to 326 of Q9BSH7, corresponding to amino acids 1 to 326 of T39971_P11 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAECKPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGVLDPDYPRNISDGFDGIPDNVDAALALPAHSYSGRERVYFFKGKQYWEYQFQH A first amino acid sequence at least 90% homologous to PSQEECEGSSLSAVFEHFAM MQRDWEDFIWGRTS, and a second amino acid sequence comprising at least 90% homology to DKYYRVNLRTRRVDTVDPPYPRSIAQYWLGCPAPGHL corresponding to amino acids 442-478 of Q9BSH7 and also corresponding to amino acids 324-363 of T39971_P11 An isolated chimeric polypeptide encoding T39971_P11, wherein said first and second amino acid sequences are in contiguous and sequential order.

  2. Length “n” (wherein n is at least about 10 amino acids long, optionally at least about 20 amino acids long, preferably at least about 30 amino acids long, more preferably at least about 40 amino acids long, most preferably at least about 50 amino acids long, at least two amino acids comprising SD, starting from any of the following structures: amino acids nos. 326-x to 326, amino acids nos. 327 + ((n-2)-x) (formula An isolated chimeric polypeptide encoding the edge portion of T39971_P11, comprising a polypeptide, having a sequence terminating in:

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The mutein is considered to be positioned as follows with respect to secretory cells. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein T39971_P11 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing the other amino acids, and listing the other amino acids, as shown in Table 50), the last column shows the SNPs It indicates whether it is known and the presence of a known SNP in the mutein T39971_P11 sequence supports the deduced sequence of this mutein of the invention).

  The mutein T39971_P11 is encoded by the following transcript: T39971_T12 (sequences shown at the end of the application). The coding portion of transcript T39971_T12 is shown in bold and this coding portion starts from position 756 and ends at position 1844. The transcript also has the following SNPs listed in Table 51 (showing its position on the nucleotide acid sequence, listing another nucleic acid, and the last column indicating if the SNP is known, a mutein The presence of known SNPs in the T39971_P11 sequence supports the deduced sequence of this mutant protein of the invention).

  The mutein T39971_P12 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript T39971_T16. An alignment to a known protein (vitronectin precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between T39971_P12 and VTNC_HUMAN 1. Corresponding to amino acids 1-223 of VTNC_HUMAN, first amino acid sequence at least 90% homologous to the corresponding MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAECKPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKTYLFK to amino acids 1-223 of T39971_P12, corresponding to amino acids 224-238 of T39971_P12 sequence VPGAVGQ A polypeptide comprising RKHLGRV and a second amino acid sequence which is at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous; An isolated chimeric polypeptide encoding T39971_P12, wherein the first and second amino acid sequences are in contiguous and sequential order.

  2. T39971_P12 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence VPGAVGQGRKHLRVR in T39971_P12 An isolated polypeptide encoding a tail.

Report of comparison between T39971_P12 and Q9BSH7 1. Corresponding to amino acids 1-223 of Q9BSH7, first amino acid sequence at least 90% homologous to the corresponding MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAECKPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKTYLFK to amino acids 1-223 of T39971_P12, corresponding to amino acids 224-238 of T39971_P12 sequence VPGAVGQGRKH A polypeptide comprising GRV and a second amino acid sequence at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous; An isolated chimeric polypeptide encoding T39971_P12, wherein the first and second amino acid sequences are in contiguous and sequential order.

  2. T39971_P12 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence VPGAVGQGRKHLRVR in T39971_P12 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The mutein is considered to be positioned as follows with respect to secretory cells. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein T39971_P12 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows SNPs as shown in Table 52) It is shown whether it is known and the presence of a known SNP in the mutein T39971_P12 sequence supports the deduced sequence of this mutein of the invention).

  The mutein T39971_P12 is encoded by the following transcript: T39971_T16 (sequences shown at the end of the application). The coding portion of the transcript T39971_T16 is shown in bold, starting from position 756 and ending at position 1469. The transcript also has the following SNPs listed in Table 53 (showing its position on the nucleotide acid sequence, listing another nucleic acid, and the last column indicating if the SNP is known, a mutein The presence of known SNPs in the T39971_P12 sequence supports the deduced sequence of this mutant protein of the invention).

  As mentioned above, cluster T39971 is characterized by the 28 segments listed in Table 41 above, the sequence of which is shown at the end of the application. These segments are part of the nucleic acid sequence, which are of particular interest and are individually described herein. A description of each segment of the invention is provided herein.

  The segment cluster T39971_node_0 of the present invention is supported by 76 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: T39971_T10, T39971_T12, T39971_T16, and T39971_T5. Table 54 below describes the start and end positions of this segment on each transcript.

  The segment cluster T39971_node_18 of the present invention is supported by one library. The number of libraries was determined as described above. This segment can be found in the following transcript: T39971_T16. Table 55 below describes the start and end positions of this segment on each transcript.

  The segment cluster T39971_node_21 of the present invention is supported by 99 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T39971_T10, T39971_T12, and T39971_T5. Table 56 below describes the start and end positions of this segment on each transcript.

  The segment cluster T39971_node_22 of the present invention is supported by seven libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T39971_T5. Table 57 below describes the start and end positions of this segment on each transcript.

  The segment cluster T39971_node_23 of the present invention is supported by 101 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T39971_T10, T39971_T12, and T39971_T5. Table 58 below describes the beginning and ending positions of this segment on each transcript.

  The segment cluster T39971_node_31 of the present invention is supported by 94 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T39971_T10 and T39971_T5. Table 59 below describes the start and end positions of this segment on each transcript.

  The segment cluster T39971_node_33 of the present invention is supported by 77 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T39971_T10, T39971_T12, and T39971_T5. Table 60 below describes the start and end positions of this segment on each transcript.

  The segment cluster T39971_node_7 of the present invention is supported by 87 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: T39971_T10, T39971_T12, T39971_T16, and T39971_T5. Table 61 below describes the start and end positions of this segment on each transcript.

  According to an optional embodiment of the present invention, there is also provided a short segment associated with the above cluster. These segments are up to about 120 bp in length and are therefore included in the individual descriptions.

  The segment cluster T39971_node_1 according to the invention can be found in the following transcripts: T39971_T10, T39971_T12, T39971_T16, and T39971_T5. Table 62 below describes the beginning and ending positions of this segment on each transcript.

  The segment cluster T39971_node_10 of the present invention is supported by 77 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: T39971_T10, T39971_T12, T39971_T16, and T39971_T5. Table 63 below describes the start and end positions of this segment on each transcript.

  The segment cluster T39971_node_11 of the present invention is supported by 79 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: T39971_T10, T39971_T12, T39971_T16, and T39971_T5. Table 64 below describes the start and end positions of this segment on each transcript.

  The segment cluster T39971_node_12 according to the invention can be found in the following transcripts: T39971_T10, T39971_T12, T39971_T16, and T39971_T5. Table 65 below describes the start and end positions of this segment on each transcript.

  The segment cluster T39971_node_15 of the present invention is supported by 79 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: T39971_T10, T39971_T12, T39971_T16, and T39971_T5. Table 66 below describes the start and end positions of this segment on each transcript.

  The segment cluster T39971_node_16 of the invention can be found in the following transcripts: T39971_T10, T39971_T12, T39971_T16, and T39971_T5. Table 67 below lists the start and end positions of this segment on each transcript.

  The segment cluster T39971_node_17 of the present invention is supported by 86 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: T39971_T10, T39971_T12, T39971_T16, and T39971_T5. Table 68 below describes the start and end positions of this segment on each transcript.

  The segment cluster T39971_node_26 of the present invention is supported by 85 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T39971_T5. Table 69 below describes the start and end positions of this segment on each transcript.

  The segment cluster T39971_node_27 of the present invention is supported by 90 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T39971_T5. Table 70 below describes the start and end positions of this segment on each transcript.

  The segment cluster T39971_node_28 according to the invention can be found in the following transcript: T39971_T10 and T39971_T5. Table 71 below lists the start and end positions of this segment on each transcript.

  The segment cluster T39971_node_29 of the present invention is supported by 99 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T39971_T10 and T39971_T5. Table 72 below lists the start and end positions of this segment on each transcript.

  The segment cluster T39971_node_3 of the present invention is supported by 78 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: T39971_T10, T39971_T12, T39971_T16, and T39971_T5. Table 73 below lists the start and end positions of this segment on each transcript.

  The segment cluster T39971_node_30 of the invention can be found in the following transcripts: T39971_T10 and T39971_T5. Table 74 below lists the start and end positions of this segment on each transcript.

  The segment cluster T39971_node_34 of the invention can be found in the following transcripts: T39971_T10, T39971_T12, and T39971_T5. Table 75 below lists the start and end positions of this segment on each transcript.

  The segment cluster T39971_node_35 of the invention can be found in the following transcripts: T39971_T10, T39971_T12, and T39971_T5. Table 76 below lists the start and end positions of this segment on each transcript.

  The segment cluster T39971_node_36 of the present invention is supported by 51 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T39971_T10, T39971_T12, and T39971_T5. Table 77 below lists the start and end positions of this segment on each transcript.

  The segment cluster T39971_node_4 according to the invention can be found in the following transcripts: T39971_T10, T39971_T12, T39971_T16, and T39971_T5. Table 78 below describes the start and end positions of this segment on each transcript.

  The segment cluster T39971_node_5 of the present invention is supported by 80 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: T39971_T10, T39971_T12, T39971_T16, and T39971_T5. Table 79 below describes the start and end positions of this segment on each transcript.

  The segment cluster T39971_node_8 of the invention can be found in the following transcripts: T39971_T10, T39971_T16, and T39971_T5. Table 80 below describes the start and end positions of this segment on each transcript.

  The segment cluster T39971_node_9 of the invention can be found in the following transcripts: T39971_T10, T39971_T12, T39971_T16, and T39971_T5. Table 81 below describes the start and end positions of this segment on each transcript.

Mutated protein alignment against previously known proteins:
Sequence name: / tmp / xkraCL2OcZ / 43L7YcPH7x: VTNC_HUMAN

Sequence documentation:

Alignment of: T39971_P6 x VTNC_HUMAN ..

Alignment segment 1/1:

Quality: 2774.00 Escore: 0
Matching length: 278 Total length: 278
Matching Percent Similarity: 99.64 Matching Percent Identity: 99.64
Total Percent Similarity: 99.64 Total Percent Identity: 99.64
Gaps: 0

Alignment:
....
1 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCCQCDECSYYQSC 50
||||||||||||||||||||||||||||||||||||||||
1 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCCQCDECSYYQSC 50
....
51 CTDYTAECKPQVTRGDVFTMPTEPEYTVYDDGEEKNNATVHEQVGGPSLTS 100
||||||||||||||||||||||||||||||||||||||||
51 CTDYTAECKPQVTRGDVFTMPTEPEYTVYDDGEEKNNATVHEQVGGPSLTS 100
....
101 DLQAQKGNPQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPP 150
||||||||||||||||||||||||||||||||||||||||
101 DLQAQKGNPQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPP 150
....
151 AEEELCSGKPFDFFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVW 200
||||||||||||||||||||||||||||||||||||||||
151 AEEELCSGKPFDFFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVW 200
....
201 GIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGLPLDPDYPRNIDGFDGI 250
||||||||||||||||||||||||||||||||||||||||
201 GIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGLPLDPDYPRNIDGFDGI 250
.
251 PDNVDAALALPAHSYSGRERVYFFKGTQ 278
||||||||||||||||||||||||
251 PDNVDAALALPAHSYSGRERVYFFKGKQ 278






Sequence name: / tmp / X4DeeuSlB4 / yMubSR5FPs: VTNC_HUMAN

Sequence documentation:

Alignment of: T39971_P9 x VTNC_HUMAN ..

Alignment segment 1/1:

Quality: 4430.00 Escore: 0
Matching length: 447 Total length: 478
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 93.51 Total Percent Identity: 93.51
Gaps: 1

Alignment:
....
1 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCCQCDECSYYQSC 50
||||||||||||||||||||||||||||||||||||||||
1 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCCQCDECSYYQSC 50
....
51 CTDYTAECKPQVTRGDVFTMPTEPEYTVYDDGEEKNNATVHEQVGGPSLTS 100
||||||||||||||||||||||||||||||||||||||||
51 CTDYTAECKPQVTRGDVFTMPTEPEYTVYDDGEEKNNATVHEQVGGPSLTS 100
....
101 DLQAQKGNPQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPP 150
||||||||||||||||||||||||||||||||||||||||
101 DLQAQKGNPQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPP 150
....
151 AEEELCSGKPFDFFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVW 200
||||||||||||||||||||||||||||||||||||||||
151 AEEELCSGKPFDFFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVW 200
....
201 GIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGLPLDPDYPRNIDGFDGI 250
||||||||||||||||||||||||||||||||||||||||
201 GIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGLPLDPDYPRNIDGFDGI 250
....
251 PDNVDAALALPAHSYSGRERVYFFKGKQYWEYQFQHQPSQEECEGSSLSA 300
||||||||||||||||||||||||||||||||||||||||
251 PDNVDAALALPAHSYSGRERVYFFKGKQYWEYQFQHQPSQEECEGSSLSA 300
....
301 VFEHFAM MQ RDSWEDIF ELFWGRT ..................................... 325
||||||||||||||||||||||||
301 VFEHFAMMQRDWSEDIFELLF WGRTS AGTRQPQ FISRDWGHVPGQVDAAM 350
....
326 ...... SGMAPRPSLAKKQRFRHRNRKGYRSQRGHSRGRNQNSRRPSRAT 369
||||||||||||||||||||||||||||||||||||||
351 AGRIYISGMAPRPSLAKKQRFRHRNRKGYRSQRGHSRGRNQNSRRPSRAT 400
....
370 WLSLFSSEESNLGANNYDDYRMDWLV PATCEPIQSFFFFSGDKYYRVNLR 419
||||||||||||||||||||||||||||||||||||||||
401 WLSLFSSEESNLGANNYDDYRMDWLV PATCEPIQSVFFFSGDKYYRVNLR 450
.
420 TRRVDTVDPPYPRSIAQYWLGCPAPGHL 447
||||||||||||||||||||||||||
451 TRRVDTVDPPYPRSIAQYWLGCPAPGHL 478






Sequence name: / tmp / jvp1VtnxNy / wxNSeFVZZw: VTNC_HUMAN

Sequence documentation:

Alignment of: T39971_P11 x VTNC_HUMAN ..

Alignment segment 1/1:

Quality: 3576.00 Escore: 0
Matching length: 363 Total length: 478
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 75.94 Total Percent Identity: 75.94
Gaps: 1

Alignment:
....
1 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCCQCDECSYYQSC 50
||||||||||||||||||||||||||||||||||||||||
1 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCCQCDECSYYQSC 50
....
51 CTDYTAECKPQVTRGDVFTMPTEPEYTVYDDGEEKNNATVHEQVGGPSLTS 100
||||||||||||||||||||||||||||||||||||||||
51 CTDYTAECKPQVTRGDVFTMPTEPEYTVYDDGEEKNNATVHEQVGGPSLTS 100
....
101 DLQAQKGNPQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPP 150
||||||||||||||||||||||||||||||||||||||||
101 DLQAQKGNPQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPP 150
....
151 AEEELCSGKPFDFFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVW 200
||||||||||||||||||||||||||||||||||||||||
151 AEEELCSGKPFDFFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVW 200
....
201 GIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGLPLDPDYPRNIDGFDGI 250
||||||||||||||||||||||||||||||||||||||||
201 GIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGLPLDPDYPRNIDGFDGI 250
....
251 PDNVDAALALPAHSYSGRERVYFFKGKQYWEYQFQHQPSQEECEGSSLSA 300
||||||||||||||||||||||||||||||||||||||||
251 PDNVDAALALPAHSYSGRERVYFFKGKQYWEYQFQHQPSQEECEGSSLSA 300
....
301 VFEHFAMMQRDWSEDIFELLFWGRTS ......................... 326
||||||||||||||||||||||||
301 VFEHFAMMQRDWSEDIFELLF WGRTS AGTRQPQ FISRDWGHVPGQVDAAM 350
....
326 ...................................................... 326

351 AGRIYISGMAPRPSLAKKQRFRHRNRKGYRSQRGHSRGRNQNSRRPSRAT 400
....
327 ..................................... DKYYRVNLR 335
|||||||||
401 WLSLFSSEESNLGANNYDDYRMDWLV PATCEPIQSVFFFSGDKYYRVNLR 450
.
336 TRRVDTVDPPYPRSIAQYWLGCPAPGHL 363
||||||||||||||||||||||||||
451 TRRVDTVDPPYPRSIAQYWLGCPAPGHL 478






Sequence name: / tmp / jvp1VtnxNy / wxNSeFVZZw: Q9BSH7

Sequence documentation:

Alignment of: T39971_P11 x Q9BSH7 ..

Alignment segment 1/1:

Quality: 3576.00 Escore: 0
Matching length: 363 Total length: 478
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 75.94 Total Percent Identity: 75.94
Gaps: 1

Alignment:
....
1 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCCQCDECSYYQSC 50
||||||||||||||||||||||||||||||||||||||||
1 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCCQCDECSYYQSC 50
....
51 CTDYTAECKPQVTRGDVFTMPTEPEYTVYDDGEEKNNATVHEQVGGPSLTS 100
||||||||||||||||||||||||||||||||||||||||
51 CTDYTAECKPQVTRGDVFTMPTEPEYTVYDDGEEKNNATVHEQVGGPSLTS 100
....
101 DLQAQKGNPQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPP 150
||||||||||||||||||||||||||||||||||||||||
101 DLQAQKGNPQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPP 150
....
151 AEEELCSGKPFDFFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVW 200
||||||||||||||||||||||||||||||||||||||||
151 AEEELCSGKPFDFFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVW 200
....
201 GIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGLPLDPDYPRNIDGFDGI 250
||||||||||||||||||||||||||||||||||||||||
201 GIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGLPLDPDYPRNIDGFDGI 250
....
251 PDNVDAALALPAHSYSGRERVYFFKGKQYWEYQFQHQPSQEECEGSSLSA 300
||||||||||||||||||||||||||||||||||||||||
251 PDNVDAALALPAHSYSGRERVYFFKGKQYWEYQFQHQPSQEECEGSSLSA 300
....
301 VFEHFAMMQRDWSEDIFELLFWGRTS ......................... 326
||||||||||||||||||||||||
301 VFEHFAMMQRDWSEDIFELLF WGRTS AGTRQPQ FISRDWGHVPGQVDAAM 350
....
326 ...................................................... 326

351 AGRIYISGMAPRPSLAKKQRFRHRNRKGYRSQRGHSRGRNQNSRRPSRAM 400
....
327 ..................................... DKYYRVNLR 335
|||||||||
401 WLSLFSSEESNLGANNYDDYRMDWLV PATCEPIQSVFFFSGDKYYRVNLR 450
.
336 TRRVDTVDPPYPRSIAQYWLGCPAPGHL 363
||||||||||||||||||||||||||
451 TRRVDTVDPPYPRSIAQYWLGCPAPGHL 478






Sequence name: / tmp / fgebv7ir4i / 48bTBMziJ0: VTNC_HUMAN

Sequence documentation:

Alignment of: T39971_P12 x VTNC_HUMAN ..

Alignment segment 1/1:

Quality: 2237.00 Escore: 0
Matching length: 223 Total length: 223
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCCQCDECSYYQSC 50
||||||||||||||||||||||||||||||||||||||||
1 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCCQCDECSYYQSC 50
....
51 CTDYTAECKPQVTRGDVFTMPTEPEYTVYDDGEEKNNATVHEQVGGPSLTS 100
||||||||||||||||||||||||||||||||||||||||
51 CTDYTAECKPQVTRGDVFTMPTEPEYTVYDDGEEKNNATVHEQVGGPSLTS 100
....
101 DLQAQKGNPQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPP 150
||||||||||||||||||||||||||||||||||||||||
101 DLQAQKGNPQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPP 150
....
151 AEEELCSGKPFDFFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVW 200
||||||||||||||||||||||||||||||||||||||||
151 AEEELCSGKPFDFFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVW 200
.
201 GIEGPIDAAFTRINCQGKTYLFK 223
||||||||||||||||||||||
201 GIEGPIDAAFTRINCQGKTYLFK 223






Sequence name: / tmp / fgebv7ir4i / 48bTBMziJ0: Q9BSH7

Sequence documentation:

Alignment of: T39971_P12 x Q9BSH7 ..

Alignment segment 1/1:

Quality: 2237.00 Escore: 0
Matching length: 223 Total length: 223
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCCQCDECSYYQSC 50
||||||||||||||||||||||||||||||||||||||||
1 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCCQCDECSYYQSC 50
....
51 CTDYTAECKPQVTRGDVFTMPTEPEYTVYDDGEEKNNATVHEQVGGPSLTS 100
||||||||||||||||||||||||||||||||||||||||
51 CTDYTAECKPQVTRGDVFTMPTEPEYTVYDDGEEKNNATVHEQVGGPSLTS 100
....
101 DLQAQKGNPQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPP 150
||||||||||||||||||||||||||||||||||||||||
101 DLQAQKGNPQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPP 150
....
151 AEEELCSGKPFDFFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVW 200
||||||||||||||||||||||||||||||||||||||||
151 AEEELCSGKPFDFFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVW 200
.
201 GIEGPIDAAFTRINCQGKTYLFK 223
||||||||||||||||||||||
201 GIEGPIDAAFTRINCQGKTYLFK 223

Description of Cluster Z21368 Cluster Z21368 features 7 transcripts of interest and 34 segments, the names of which are shown in Tables 82 and 83, respectively, and the sequence itself is shown at the end of the application. Selected protein variants are shown in Table 84.

  These sequences are known as extracellular sulfatase Sulf-1 precursor (SwissProt accession identifier SUL1_HUMAN, synonym EC1. Is also a variant of (SEQ ID NO: 1419).

  The protein extracellular sulfatase Sulf-1 precursor is known or considered to have the following functions: It exhibits arylsulfatase activity and highly specific endoglucosamine-6-sulfatase activity. This can remove the sulfate from the C-6 position of glucosamine in certain sub-zones of intact heparin. It reduces HSPG (heparan sulfate proteoglycan) sulfation, inhibits heparin-dependent growth factor signaling, reduces proliferation and facilitates apoptosis in response to exogenous stimuli. The sequence of the extracellular sulfatase Sulf-1 precursor is shown at the end of the application as "extracellular sulfatase Sulf-1 precursor amino acid sequence". Known polymorphisms of this sequence are shown in Table 85.

  Localization of the protein extracellular sulfatase Sulf-1 precursor is considered to be the endoplasmic reticulum and Golgi lamina. It is also localized on the cell surface (due to similarity).

  The following GO annotation applies to previously known proteins. The following annotations have been found: related to biological processes, such as apoptosis, metabolism, heparan sulfate proteoglycan metabolism, arylsulfatases that are related to molecular function, hydrolases, and cellular components. Annotated extracellular space, endoplasmic reticulum, Golgi stack.

  GO assignments can be made at one or more http: // www. expasy. SwissProt / TremBl Protein knowledgebase available from ch / sprot / or http: // www. ncbi. nlm. nih. Depends on Locuslink available from gov / projects / LocusLink /.

  Cluster Z21368 can be used as a diagnostic marker by overexpression of transcripts of this cluster in cancer. The expression of such transcripts in normal tissues is also shown by the method previously described. The terms "numbers" in the right column of the table and the numbers on the y-axis of Fig. 13 refer to the weighted expression of ESTs in each category as "ppm" (the ppm of ESTs of a particular cluster in this category by ppm Ratio of expression to expression of all ESTs).

  In general, as shown for the histograms in FIG. 13 and Table 86, the following results were obtained. This cluster was overexpressed (at least at minimal levels) in the following pathological conditions: epithelial malignant brain tumors, a mixture of malignant tumors from different tissues, and pancreatic cancer.

  As mentioned above, cluster Z21368 is characterized by the seven transcripts listed in Table 1 above. These transcripts encode proteins which are variants of the protein extracellular sulfatase Sulf-1 precursor. A description of each mutein of the invention is provided herein.

  The mutein Z21368_PEA_1_P2 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript Z21368_PEA_1_T5. An alignment to a known protein (extracellular sulfatase Sulf-1 precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report on comparison of Z21368_PEA_1_P2 with SUL1_HUMAN 1. Corresponding to amino acids 1 to 761 of SUL1_HUMAN, corresponding to amino acids 1 to 761 of Z21368_PEA_1_P2 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSLQVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESINYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYNYAPNMDKHWIMQYTGPMLPIHMEFTNI QRKRLQTLMSVDDSVERLYNMLVETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEPGSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLPKYERVKELCQQARYQTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYARGFHDKDKECSCRESGYRASRSQRKSQRQFLRNQGTPKYKPRFVHTRQTRSLSVEFEGEIYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLADSSNAVGPPT A first amino acid sequence at least 90% homologous to BuiarubuitieichikeishiefuaieruPienudiesuaieichishiiaruieruwaikyuesueiarueidaburyukeidieichikeieiwaiaidikeiiaiieierukyudikeiaikeienueruaruibuiarujieichierukeiaruarukeiPiiishiesushiesukeikyuesuwaiwaienukeiikeijibuikeikeikyuikeierukeiesueichierueichiPiefukeiieieikyuibuidiesukeierukyueruefukeiienuenuaruaruarukeikeiiarukeiikeiaruarukyuarukeijiEECSLPGLTCFTHDNNHWQTAPFWN, polypeptide at least 70% with a sequence corresponding to PHKYSAHGRTRHFESATRTTNGAQKLSRI to amino acid 762-790 of Z21368_PEA_1_P2, optionally at least 80%, preferably at least 85%, more preferably Comprises a second amino acid sequence which is at least 90%, most preferably at least 95% homologous, and An isolated chimeric polypeptide encoding Z21368_PEA_1_P2, wherein said first and second amino acid sequences are in contiguous and sequential order.

  2. Z21368_PEA_1_P2 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence PHKYSAHGRTRHFESATRTTNGAQKLSRI in Z21368_PEA_1_P2 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The mutein is considered to be positioned as follows with respect to secretory cells. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein Z21368_PEA_1_P2 is encoded by the following transcript: Z21368_PEA_1_T5 (sequences shown at the end of the application). The code portion of the transcript Z21368_PEA_1_T5 is shown in bold, starting from position 529 and ending at position 2898.

  The mutein Z21368_PEA_1_P5 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript Z21368_PEA_1_T9. An alignment to a known protein (extracellular sulfatase Sulf-1 precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report on comparison of Z21368_PEA_1_P5 with Q7Z2W2 (SEQ ID NO: 1697). MKYSCCALVLAGLTEL GSL CST VRSPR SPR VRSPR FRG IQ corresponding to amino acids 1 to 57 of Q7Z2W2 and also to amino acids 1 to 57 of Z21368_PEA_1_P5 A first amino acid sequence that is at least 90% homologous to DER Q Corresponding to 871 and corresponding to amino acids 59 to 791 of Z21368_PEA_1_P5 FFGKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESINYFKMSYMMYPMRPVMVMISAPHGPEDSAPQFSKLYPNASQHITPSYNYAPNMDKHWIPLPIP HMEFTNILQRKRLQTLMSVDDSVERLYNMLVETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEPGSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLPKYERVKELCQQARYQTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYARGFHDKDKECSCRESGYRASRSQRKSQRQFLRNQGTPKYKPRFVHTRQTRSLSVEFEGEIYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLADS NAVGPPTTVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEIEALQDKIKNLREVRGHLKRRKPEECSCSKQSYYNKEKGVKKQEKLKSHLHPFKEAAQEVDSKLQLFKENNRRRKKERKEKRRQRKGEECSLPGLTCFTHDNNHWQTAPFWNLGSFCACTSSNNNTYWCLRTVNETHNFLFCEFATGFLEYFDMNTDPYQLTNTVHTVERGILNQLHVQLMELRSCQGYKQCNPRPKNLDVGNKDGGSYDLHRGQLWDGWEG and and at least 90% homologous to a third amino acid sequence, wherein the first, second, and third amino acid distribution is in the order in which adjacent and contiguous, Z2 An isolated chimeric polypeptide encoding 1368_PEA_1_P5.

  2. Length “n” (wherein n is at least about 10 amino acids long, optionally at least about 20 amino acids long, preferably at least about 30 amino acids long, more preferably at least about 40 amino acids long, most preferably at least about 50 amino acids long, at least two amino acids comprising LAF, the following structure (numbering corresponding to Z21368_PEA_1_P5): starting from any of amino acid numbers 57-x to 57, amino acid number 59+ ((n -2)-x) An isolated polypeptide encoding the edge portion of Z21368_PEA_1_P5, comprising a polypeptide, having a sequence terminating at: where x varies from 0 to n-2.

Report on the comparison of Z21368_PEA_1_P5 with AAH12997 (SEQ ID NO: 1698). Corresponding to amino acids 1 to 751 of Z21368_PEA_1_P5 array MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELAFFGKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESINYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYNYAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNMLVETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEPGSIVPQIVLNIDLAPTILDIAGLDTPPDVD KSVLKLLDPEKPGNRFRTNKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLPKYERVKELCQQARYQTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYARGFHDKDKECSCRESGYRASRSQRKSQRQFLRNQGTPKYKPRFVHTRQTRSLSVEFEGEIYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLADSSNAVGPPTTVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEIEALQDKIKNLREVRGHLKRRKPEECSCSKQSYYNKEKGVKKQEKLKSHLHPFKEAAQEVDSKLQ FKENNRRRKKERKEKRRQRKGEECSLPGLTCFTHDNHNHQQTAPFWNLGSFCACTSSNNNTYWCLRTTVNETHNFLFCEFATGFLEYFDM T FLYNTTVHTVERGILN QL HTV QLME With a polypeptide having at least 70%, optionally at least 80%, preferably at least 85%, preferably at least 90%, most preferably at least 95H, To 40, and also to amino acids 752-791 of Z21368_PEA_1_P5, which comprises a second amino acid sequence that is at least 90% homologous to LRSCQGYKQ CNPRP KNLD GGN KD GSY DL HR G QLG WDEGEG, An isolated chimeric polypeptide encoding Z21368_PEA_1_P5, wherein the first and second amino acid sequences are in contiguous and sequential order.

  2. Array of Z21368_PEA_1_P5 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELAFFGKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESINYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYNYAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNMLVETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEPGSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPG RFRTNKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLPKYERVKELCQQARYQTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYARGFHDKDKECSCRESGYRASRSQRKSQRQFLRNQGTPKYKPRFVHTRQTRSLSVEFEGEIYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLADSSNAVGPPTTVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEIEALQDKIKNLREVRGHLKRRKPEECSCSKQSYYNKEKGVKKQEKLKSHLHPFKEAAQEVDSKLQLFKENNRRRKKERK And at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous polypeptide H. Isolated polypeptide.

Report on comparison of Z21368_PEA_1_P5 with SUL1_HUMAN 1. The first amino acid sequence corresponding to amino acids 1 to 57 of SUL1_HUMAN and corresponding to amino acids 1 to 57 of Z21368_PEA_1_P5 MKYSCCALVLGELLTGSL CST VRSRPRSPRFTRGRIQQERKNIRPNIILVLTDQDVEL corresponding to amino acids 138 to 871 of SUL1_HUMAN, corresponding to amino acids 138 to 871 of SUL1_HUMAN Also corresponding to AFFGKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCRNGIKE KHGFDYAKDYFTDLITNESINYFK MS KRMMY PHRP VMVM VISHA PHGP EDSAPQ FSKLY PNAS QTPSYNYAPNMDKHWIMQYPTGPMLPIHMEFTNI QRKRLQTLMSVDDSVERLYNMLVETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEPGSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLPKYERVKELCQQARYQTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYARGFHDKDKECSCRESGYRASRSQRKSQRQFLRNQGTPKYKPRFVHTRQTRSLSVEFEGEIYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLADSSNAVGPPT VRVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEIEALQDKIKNLREVRGHLKRRKPEECSCSKQSYYNKEKGVKKQEKLKSHLHPFKEAAQEVDSKLQLFKENNRRRKKERKEKRRQRKGEECSLPGLTCFTHDNNHWQTAPFWNLGSFCACTSSNNNTYWCLRTVNETHNFLFCEFATGFLEYFDMNTDPYQLTNTVHTVERGILNQLHVQLMELRSCQGYKQCNPRPKNLDVGNKDGGSYDLHRGQLWDGWEG and and at least 90% homologous to a second amino acid sequence, wherein the first and second amino acid distribution is contiguous, and in sequential order, Z21368_PEA_1_P 5. An isolated chimeric polypeptide encoding 5.

  2. Length “n” (wherein n is at least about 10 amino acids long, optionally at least about 20 amino acids long, preferably at least about 30 amino acids long, more preferably at least about 40 amino acids long, most preferably at least about 50 amino acids in length, at least two amino acids comprising LA, starting from any of the following structures: amino acid numbers 57-x to 57, amino acid numbers 58 + ((n-2) -x) (formula An isolated chimeric polypeptide encoding an edge portion of Z21368_PEA_1_T5, comprising a polypeptide, having a sequence terminating in:), wherein x varies from 0 to n-2.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The mutein is considered to be positioned as follows with respect to secretory cells. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein Z21368_PEA_1_P5 is encoded by the following transcript: Z21368_PEA_1_T9 (sequences shown at the end of the application). The code portion of the transcript Z21368_PEA_1_T9 is shown in bold, starting from position 556 and ending at position 2928.

  The mutein Z21368_PEA_1_P15 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript Z21368_PEA_1_T23. An alignment to a known protein (extracellular sulfatase Sulf-1 precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report on comparison of Z21368_PEA_1_P15 with SUL1_HUMAN 1. Corresponding to amino acids 1 to 416 of SUL1_HUMAN, corresponding to amino acids 1 to 416 of Z21368_PEA_1_P15 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSLQVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESINYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYNYAPNMDKHWIMQYTGPMLPIHMEFTN LQRKRLQTLMSVDDSVERLYNMLVETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEPGSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFLVERG and containing at least 90% homologous first amino acid sequence, isolated chimeric polypeptide coding Z21368_PEA_1_P15.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The mutein is considered to be positioned as follows with respect to secretory cells. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein Z21368_PEA_1_P15 is encoded by the following transcript: Z21368_PEA_1_T23 (sequences shown at the end of the application). The code portion of the transcript Z21368_PEA_1_T23 is shown in bold, starting from position 691 and ending at position 1938.

  The mutein Z21368_PEA_1_P16 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript Z21368_PEA_1_T24. An alignment to a known protein (extracellular sulfatase Sulf-1 precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report on comparison of Z21368_PEA_1_P16 with SUL1_HUMAN 1. Corresponding to amino acids 1 to 397 of SUL1_HUMAN, corresponding to amino acids 1 to 397 of Z21368_PEA_1_P16 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSLQVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESINYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYNYAPNMDKHWIMQYTGPMLPIHMEFTN LQRKRLQTLMSVDDSVERLYNMLVETYII YTADHGYHIGQFGLVKGKSMPYDFDIRVPFIRGPSVEPGSIVPQIV IVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEPKNR A first amino acid sequence of Z21368_PEA_1_P16, a sequence of 3 to 45 ° C, Is at least 90%, most preferably at least 95% homologous, with a second amino acid sequence, said first and second amino acid sequences being adjacent and in consecutive order, Z21368_PEA_ Isolated chimeric polypeptide encoding _P16.

  2. The Z21368_PEA_1_P16 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 90%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence CVIVPPLSQPQIH in Z21368_PEA_1_P16 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The mutein is considered to be positioned as follows with respect to secretory cells. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein Z21368_PEA_1_P16 is encoded by the following transcript: Z21368_PEA_1_T24 (sequences shown at the end of the application). The code portion of the transcript Z21368_PEA_1_T24 is shown in bold, starting at position 691 and ending at position 1920.

  The mutein Z21368_PEA_1_P22 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript Z21368_PEA_1_T10. An alignment to a known protein (extracellular sulfatase Sulf-1 precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report on comparison of Z21368_PEA_1_P22 with SUL1_HUMAN 1. Corresponding to amino acids 1-188 of SUL1_HUMAN, Poripepu having a MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSLQVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAK corresponding to amino acids 1-188 of Z21368_PEA_1_P22 the first amino acid sequence at least 90% homologous, sequences corresponding to ARYDGDQPRCAPRPRGLSPTVF to amino acid 189-210 of Z21368_PEA_1_P22 And a second amino acid sequence which is at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous, said first and second An isolated chimeric polypeptide encoding Z21368_PEA_1_P22, wherein the amino acid sequences of are in the contiguous and sequential order.

  2. Z21368_PEA_1_P22 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence ARYDGDQPRCAPRPRGSPTVF in Z21368_PEA_1_P22 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The mutein is considered to be positioned as follows with respect to secretory cells. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein Z21368_PEA_1_P22 is encoded by the following transcript: Z21368_PEA_1_T10 (sequences shown at the end of the application). The code portion of transcript Z21368_PEA_1_T10 is shown in bold, starting at position 691 and ending at position 1320.

  The mutein Z21368_PEA_1_P23 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript Z21368_PEA_1_T11. An alignment to a known protein (extracellular sulfatase Sulf-1 precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between Z21368_PEA_1_P23 and Q7Z2W2. MKYSCALVLGELLGHSLCSTVRSRSLCSTVRSPRFRGRIQQ EH which corresponds to the amino acid 1 to 137 of the Q7Z2W2 and corresponds to the amino acid 1 to 137 of the Z21368_PEA_1_P23, and it is a UFJ 7 At least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least And a 5% homologous second amino acid sequence, wherein the first and second amino acid distribution is contiguous, and in sequential order, the isolated chimeric polypeptide coding Z21368_PEA_1_P23.

  2. Z21368_PEA_1_P23 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence GLLHRLNH in Z21368_PEA_1_P23 An isolated polypeptide encoding a tail.

Report on comparison of Z21368_PEA_1_P23 with SUL1_HUMAN 1. MKYSCAL VL ELL LG LSL CST VRS PR SPR FR G R IQ Q E R K NI Q N T L T Q D Q EL T G H T GH T RF IN Q GH T H RF NG N NH Y N H Y N H Y N H Y N H Y N H H N H Y N H Y N H H At least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably small And a Kutomo 95% homologous second amino acid sequence, wherein the first and second amino acid distribution is contiguous, and in sequential order, the isolated chimeric polypeptide coding Z21368_PEA_1_P23.

  2. Z21368_PEA_1_P23 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence GLLHRLNH in Z21368_PEA_1_P23 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The mutein is considered to be positioned as follows with respect to secretory cells. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein Z21368_PEA_1_P23 is encoded by the following transcript: Z21368_PEA_1_T11 (sequences shown at the end of the application). The coding part of the transcript Z21368_PEA_1_T11 is shown in bold, starting from position 691 and ending at position 1125.

  As mentioned above, cluster Z21368 is characterized by the 34 segments listed in Table 2 above, the sequence of which is shown at the end of the application. These segments are part of the nucleic acid sequence, which are of particular interest and are individually described herein. A description of each segment of the invention is provided herein.

  The segment cluster Z21368_PEA_1_node_0 of the present invention is supported by eight libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: 21368_PEA_1_T9. Table 88 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z21368_PEA_1_node_15 of the present invention is supported by 26 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: Z21368_PEA_1_T10, Z21368_PEA_1_T11, Z21368_PEA_1_T23, Z21368_PEA_1_T24, Z21368_PEA_1_T5, Z21368_PEA_1_T6, and Z21368_PEA_1_T9. Table 89 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z21368_PEA_1_node_19 of the present invention is supported by 24 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: Z21368_PEA_1_T10, Z21368_PEA_1_T11, Z21368_PEA_1_T23, Z21368_PEA_1_T24, Z21368_PEA_1_T5, and Z21368_PEA_1_T6. Table 90 below lists the start and end positions of this segment on each transcript.

  The segment cluster Z21368_PEA_1_node_2 of the present invention is supported by 15 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: Z21368_PEA_1_T10, Z21368_PEA_1_T11, Z21368_PEA_1_T23, Z21368_PEA_1_T24, Z21368_PEA_1_T5, and Z21368_PEA_1_T6. Table 91 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z21368_PEA_1_node_21 of the present invention is supported by 37 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: Z21368_PEA_1_T10, Z21368_PEA_1_T23, Z21368_PEA_1_T24, Z21368_PEA_1_T5, Z21368_PEA_1_T6, and Z21368_PEA_1_T9. Table 92 below lists the start and end positions of this segment on each transcript.

  The segment cluster Z21368_PEA_1_node_33 of the present invention is supported by 45 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: Z21368_PEA_1_T10, Z21368_PEA_1_T11, Z21368_PEA_1_T23, Z21368_PEA_1_T24, Z21368_PEA_1_T5, Z21368_PEA_1_T6, and Z21368_PEA_1_T9. Table 93 below lists the start and end positions of this segment on each transcript.

  The segment cluster Z21368_PEA_1_node_36 of the present invention is supported by 44 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: Z21368_PEA_1_T10, Z21368_PEA_1_T11, Z21368_PEA_1_T23, Z21368_PEA_1_T24, Z21368_PEA_1_T5, Z21368_PEA_1_T6, and Z21368_PEA_1_T9. Table 94 below lists the start and end positions of this segment on each transcript.

  The segment cluster Z21368_PEA_1_node_37 of the present invention is supported by three libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: Z21368_PEA_1_T24. Table 95 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z21368_PEA_1_node_39 of the present invention is supported by five libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: Z21368_PEA_1_T23 and Z21368_PEA_1_T24. Table 96 below lists the start and end positions of this segment on each transcript.

  The segment cluster Z21368_PEA_1_node_4 of the present invention is supported by 13 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: Z21368_PEA_1_T10, Z21368_PEA_1_T11, Z21368_PEA_1_T23, and Z21368_PEA_1_T24. Table 97 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z21368_PEA_1_node_41 of the present invention is supported by 49 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: Z21368_PEA_1_T10, Z21368_PEA_1_T11, Z21368_PEA_1_T5, Z21368_PEA_1_T6, and Z21368_PEA_1_T9. Table 98 below lists the start and end positions of this segment on each transcript.

  The segment cluster Z21368_PEA_1_node_43 of the present invention is supported by 52 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: Z21368_PEA_1_T10, Z21368_PEA_1_T11, Z21368_PEA_1_T5, Z21368_PEA_1_T6, and Z21368_PEA_1_T9. Table 99 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z21368_PEA_1_node_45 of the present invention is supported by 64 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: Z21368_PEA_1_T10, Z21368_PEA_1_T11, Z21368_PEA_1_T5, Z21368_PEA_1_T6, and Z21368_PEA_1_T9. Table 100 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z21368_PEA_1_node_53 of the present invention is supported by 60 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: Z21368_PEA_1_T10, Z21368_PEA_1_T11, Z21368_PEA_1_T5, Z21368_PEA_1_T6, and Z21368_PEA_1_T9. Table 101 below lists the start and end positions of this segment on each transcript.

  The segment cluster Z21368_PEA_1_node_56 of the present invention is supported by 50 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: Z21368_PEA_1_T10, Z21368_PEA_1_T11, and Z21368_PEA_1_T9. Table 102 below lists the start and end positions of this segment on each transcript.

  The segment cluster Z21368_PEA_1_node_58 of the present invention is supported by 71 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: Z21368_PEA_1_T10, Z21368_PEA_1_T11, Z21368_PEA_1_T5, Z21368_PEA_1_T6, and Z21368_PEA_1_T9. Table 103 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z21368_PEA_1_node_66 of the present invention is supported by 142 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: Z21368_PEA_1_T10, Z21368_PEA_1_T11, Z21368_PEA_1_T5, Z21368_PEA_1_T6, and Z21368_PEA_1_T9. Table 104 below lists the start and end positions of this segment on each transcript.

  The segment cluster Z21368_PEA_1_node_67 of the present invention is supported by 181 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: Z21368_PEA_1_T10, Z21368_PEA_1_T11, Z21368_PEA_1_T5, Z21368_PEA_1_T6, and Z21368_PEA_1_T9. Table 105 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z21368_PEA_1_node_69 of the present invention is supported by 150 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: Z21368_PEA_1_T10, Z21368_PEA_1_T11, Z21368_PEA_1_T5, Z21368_PEA_1_T6, and Z21368_PEA_1_T9. Table 106 below describes the start and end positions of this segment on each transcript.

  According to an optional embodiment of the present invention, there is also provided a short segment associated with the above cluster. These segments are up to about 120 bp in length and are therefore included in the individual descriptions.

  The segment cluster Z21368_PEA_1_node_11 of the present invention is supported by 26 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: Z21368_PEA_1_T10, Z21368_PEA_1_T11, Z21368_PEA_1_T23, Z21368_PEA_1_T24, Z21368_PEA_1_T5, Z21368_PEA_1_T6, and Z21368_PEA_1_T9. Table 107 below lists the start and end positions of this segment on each transcript.

  The segment cluster Z21368_PEA_1_node_12 of the present invention is supported by 23 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: Z21368_PEA_1_T10, Z21368_PEA_1_T11, Z21368_PEA_1_T23, Z21368_PEA_1_T24, Z21368_PEA_1_T5, Z21368_PEA_1_T6, and Z21368_PEA_1_T9. Table 108 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z21368_PEA_1_node_16 according to the invention can be found in the following transcripts: Z21368_PEA_1_T10, Z21368_PEA_1_T11, Z21368_PEA_1_T23, Z21368_PEA_1_T24, Z21368_PEA_1_T5, Z21368_PEA_1_T6, Z21368_PEA. Table 109 below lists the start and end positions of this segment on each transcript.

  The segment cluster Z21368_PEA_1_node_17 of the present invention is supported by 19 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: Z21368_PEA_1_T10, Z21368_PEA_1_T11, Z21368_PEA_1_T23, Z21368_PEA_1_T24, Z21368_PEA_1_T5, Z21368_PEA_1_T6, and Z21368_PEA_1_T9. Table 110 below lists the start and end positions of this segment on each transcript.

  The segment cluster Z21368_PEA_1_node_23 of the present invention is supported by 36 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: Z21368_PEA_1_T11, Z21368_PEA_1_T23, Z21368_PEA_1_T24, Z21368_PEA_1_T5, Z21368_PEA_1_T6, and Z21368_PEA_1_T9. Table 111 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z21368_PEA_1_node_24 of the present invention is supported by 36 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: Z21368_PEA_1_T10, Z21368_PEA_1_T11, Z21368_PEA_1_T23, Z21368_PEA_1_T24, Z21368_PEA_1_T5, Z21368_PEA_1_T6, and Z21368_PEA_1_T9. Table 112 below lists the start and end positions of this segment on each transcript.

  The segment cluster Z21368_PEA_1_node_30 of the present invention is supported by 39 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: Z21368_PEA_1_T10, Z21368_PEA_1_T11, Z21368_PEA_1_T23, Z21368_PEA_1_T24, Z21368_PEA_1_T5, Z21368_PEA_1_T6, and Z21368_PEA_1_T9. Table 113 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z21368_PEA_1_node_31 of the present invention is supported by 40 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: Z21368_PEA_1_T10, Z21368_PEA_1_T11, Z21368_PEA_1_T23, Z21368_PEA_1_T24, Z21368_PEA_1_T5, Z21368_PEA_1_T6, and Z21368_PEA_1_T9. Table 114 below lists the start and end positions of this segment on each transcript.

  The segment cluster Z21368_PEA_1_node_38 of the present invention is supported by 45 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: Z21368_PEA_1_T10, Z21368_PEA_1_T11, Z21368_PEA_1_T23, Z21368_PEA_1_T24, Z21368_PEA_1_T5, Z21368_PEA_1_T6, and Z21368_PEA_1_T9. Table 115 below lists the start and end positions of this segment on each transcript.

  The segment cluster Z21368_PEA_1_node_47 of the present invention is supported by 61 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: Z21368_PEA_1_T10, Z21368_PEA_1_T11, Z21368_PEA_1_T5, Z21368_PEA_1_T6, and Z21368_PEA_1_T9. Table 116 below lists the start and end positions of this segment on each transcript.

  The segment cluster Z21368_PEA_1_node_49 of the present invention is supported by 57 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: Z21368_PEA_1_T10, Z21368_PEA_1_T11, Z21368_PEA_1_T5, Z21368_PEA_1_T6, and Z21368_PEA_1_T9. Table 117 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z21368_PEA_1_node_51 of the present invention is supported by 46 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: Z21368_PEA_1_T10, Z21368_PEA_1_T11, Z21368_PEA_1_T5, Z21368_PEA_1_T6, and Z21368_PEA_1_T9. Table 118 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z21368_PEA_1_node_61 of the present invention is supported by 61 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: Z21368_PEA_1_T10, Z21368_PEA_1_T11, Z21368_PEA_1_T5, Z21368_PEA_1_T6, and Z21368_PEA_1_T9. Table 119 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z21368_PEA_1_node_68 of the present invention is supported by 87 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: Z21368_PEA_1_T10, Z21368_PEA_1_T11, Z21368_PEA_1_T5, Z21368_PEA_1_T6, and Z21368_PEA_1_T9. Table 120 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z21368_PEA_1_node_7 of the present invention is supported by 29 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: Z21368_PEA_1_T10, Z21368_PEA_1_T11, Z21368_PEA_1_T23, Z21368_PEA_1_T24, Z21368_PEA_1_T5, Z21368_PEA_1_T6, and Z21368_PEA_1_T9. Table 121 below describes the start and end positions of this segment on each transcript.

  Overexpression of at least a portion of this cluster was determined by the oligonucleotide and one or more chips. The results were as follows. The oligonucleotide Z21368_0_0_61857 was provided on a TAA chip and found to be overexpressed in lung cancer (total), lung adenocarcinoma, and squamous cell carcinoma.

Mutated protein alignment against previously known proteins:
Sequence name: / tmp / 5ER3vIMKE2 / 9L0Y7lDlTQ: SUL1_HUMAN

Sequence documentation:

Alignment of: Z21368_PEA_1_P2 x SUL1_HUMAN ..

Alignment segment 1/1:

Quality: 7664.00 Escore: 0
Matching length: 761 Total length: 761
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MKYSCCALVLALGLGELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50
||||||||||||||||||||||||||||||||||||||||
1 MKYSCCALVLALGLGELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50
....
51 DDQDVELGSLQVMNKTRKIMEHGGAGTFINAFVTTPMCCPSRSSMLTGKYV 100
||||||||||||||||||||||||||||||||||||||||
51 DDQDVELGSLQVMNKTRKIMEHGGAGTFINAFVTTPMCCPSRSSMLTGKYV 100
....
101 HNHNVYTNNENC SSP SW QAM HEPRTF AVYLNNTGYRTAFFGKYLNEYNGS 150
||||||||||||||||||||||||||||||||||||||||
101 HNHNVYTNNENC SSP SW QAM HEPRTF AVYLNNTGYRTAFFGKYLNEYNGS 150
....
151 YIPPGWREWLGLIKNSRFYNYTVCRNGIKE KHGFDYAKDYFTDLITNESI 200
||||||||||||||||||||||||||||||||||||||||
151 YIPPGWREWLGLIKNSRFYNYTVCRNGIKE KHGFDYAKDYFTDLITNESI 200
....
201 NYFKMSKRMMYPHRPVMMMVISHAAPHGPEDSAPQFSKLYPNA SQIPTSYN 250
||||||||||||||||||||||||||||||||||||||||
201 NYFKMSKRMMYPHRPVMMMVISHAAPHGPEDSAPQFSKLYPNA SQIPTSYN 250
....
251 YAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNML 300
||||||||||||||||||||||||||||||||||||||||
251 YAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNML 300
....
301 VETGELENTYII YTADHGYHIGQFGLVKGKSMPYDFDIRVPFIRGPSVE 350
||||||||||||||||||||||||||||||||||||||||
301 VETGELENTYII YTADHGYHIGQFGLVKGKSMPYDFDIRVPFIRGPSVE 350
....
351 PGSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRT 400
||||||||||||||||||||||||||||||||||||||||
351 PGSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRT 400
....
401 NKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLPKYERVKELCQQARY 450
||||||||||||||||||||||||||||||||||||||||
401 NKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLPKYERVKELCQQARY 450
....
451 QTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYARGFHDK 500
||||||||||||||||||||||||||||||||||||||||
451 QTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYARGFHDK 500
....
501 DKECSCRESGYRASRSQRKSMQRQFLRNQGTPKYKPRFVHTRQTRSLSVEF 550
||||||||||||||||||||||||||||||||||||||||
501 DKECSCRESGYRASRSQRKSMQRQFLRNQGTPKYKPRFVHTRQTRSLSVEF 550
....
551 EGEIYDINLEEEEEL QVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLA 600
||||||||||||||||||||||||||||||||||||||||
551 EGEIYDINLEEEEEL QVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLA 600
....
601 DSSNAVGPPTTVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEI 650
||||||||||||||||||||||||||||||||||||||||
601 DSSNAVGPPTTVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEI 650
....
651 EALQDKIKNLREVRGHLKRRK PEECSCSKQS YYNKEKGVKKQEKLKSHLH 700
||||||||||||||||||||||||||||||||||||||||
651 EALQDKIKNLREVRGHLKRRK PEECSCSKQS YYNKEKGVKKQEKLKSHLH 700
....
701 PFKEAAQEVDSKLQLFKENNRRRKKERKEKRQRKGEECSLPGLTCFTHD 750
||||||||||||||||||||||||||||||||||||||||
701 PFKEAAQEVDSKLQLFKENNRRRKKERKEKRQRKGEECSLPGLTCFTHD 750
.
751 NNHWQTAPFWN 761
|||||||||||
751 NNHWQTAPFWN 761






Sequence name: / tmp / tt3yfXIUKV / YxSTFWr66h: Q7Z2W2

Sequence documentation:

Alignment of: Z21368_PEA_1_P5 x Q7Z2W2 ..

Alignment segment 1/1:

Quality: 7869.00 Escore: 0
Matching length: 791 Total length: 871
Matching Percent Similarity: 99.87 Matching Percent Identity: 99.87
Total Percent Similarity: 90.70 Total Percent Identity: 90.70
Gaps: 1

Alignment:
....
1 MKYSCCALVLALGLGELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50
||||||||||||||||||||||||||||||||||||||||
1 MKYSCCALVLALGLGELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50
....
51 DDQDVELA ......................................... 58
||||||||
51 DDQDVELGSLQVMNKTRKIMEHGGAGTFINAFVTTPMCCPSRSSMLTGKYV 100
....
59 ................................... FFGKYLNEYNGS 70
||||||||||||
101 HNHNVYTNNENC SSP SW QAM HEPRTF AVYLNN TG YRT VFF KKYLNEYNGS 150
....
71 YIPPGWREWLGLIKNSRFYNYTVCRNGIKE KHGFDYAKDYFTDLITNESI 120
||||||||||||||||||||||||||||||||||||||||
151 YIPPGWREWLGLIKNSRFYNYTVCRNGIKE KHGFDYAKDYFTDLITNESI 200
....
121 NYFKMSKRMMYPHRPVMMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYN 170
||||||||||||||||||||||||||||||||||||||||
201 NYFKMSKRMMYPHRPVMMMVISHAAPHGPEDSAPQFSKLYPNA SQIPTSYN 250
....
171 YAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNML 220
||||||||||||||||||||||||||||||||||||||||
251 YAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNML 300
....
221 VETGELENTYII YTADHGYHIGQFGLVKGKSMPYDFDIRVPFIRGPSVE 270
||||||||||||||||||||||||||||||||||||||||
301 VETGELENTYII YTADHGYHIGQFGLVKGKSMPYDFDIRVPFIRGPSVE 350
....
271 PGSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRT 320
||||||||||||||||||||||||||||||||||||||||
351 PGSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRT 400
....
321 NKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLPKYERVKELCQQARY 370
||||||||||||||||||||||||||||||||||||||||
401 NKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLPKYERVKELCQQARY 450
....
371 QTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYARGFHDK 420
||||||||||||||||||||||||||||||||||||||||
451 QTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYARGFHDK 500
....
421 DKECSCRSGYRASRSQRKSMQRQFLRNQGTPKYKPRFVHTRQTRSLSVEF 470
||||||||||||||||||||||||||||||||||||||||
501 DKECSCRESGYRASRSQRKSMQRQFLRNQGTPKYKPRFVHTRQTRSLSVEF 550
....
471 EGEIYDINLEEEEELQ VLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLA 520
||||||||||||||||||||||||||||||||||||||||
551 EGEIYDINLEEEEEL QVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLA 600
....
521 DSSNAVGPPTTVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEI 570
||||||||||||||||||||||||||||||||||||||||
601 DSSNAVGPPTTVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEI 650
....
571 EALQDKIKNLREVRGHLKRRK PEECSCSKQS YYNKEKGVKKQEKLKSHLH 620
||||||||||||||||||||||||||||||||||||||||
651 EALQDKIKNLREVRGHLKRRK PEECSCSKQS YYNKEKGVKKQEKLKSHLH 700
....
621 PFKEAAQEVDSKLQLFKENNRRRKKERKEKRQRKGEECSLPGLTCFTHD 670
||||||||||||||||||||||||||||||||||||||||
701 PFKEAAQEVDSKLQLFKENNRRRKKERKEKRQRKGEECSLPGLTCFTHD 750
....
671 NNHWQTAPFWNLGSFCACTSSNNNTYWCLRTVNETHNFLFCEFATGFLEY 720
||||||||||||||||||||||||||||||||||||||||
751 NNHWQTAPFWNLGSFCACTSSNNNTYWCLRTVNETHNFLFCEFATGFLEY 800
....
721 FDMNTDPYQLTNTVHTVERGILNQLHVLMELRSCQGYKQCNPRPKNLDV 770
||||||||||||||||||||||||||||||||||||||||
801 FDMNTDPYQLTNTVHTVERGILNQLHVLMELRSCQGYKQCNPRPKNLDV 850
.
771 GNKDGGSYDLHRGQLWDGWEG 791
||||||||||||||||||||
851 GNKDGGSYDLHRGQLWDGWEG 871






Sequence name: / tmp / tt3yfXIUKV / YxSTFWr66h: AAH12997

Sequence documentation:

Alignment of: Z21368_PEA_1_P5 x AAH12997 ..

Alignment segment 1/1:

Quality: 420.00 Escore: 0
Matching length: 40 Total length: 40
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
752 LRSCQGYKQ CNPRP KNLD GGN KDGGSYDLHRGQLWDGWEG 791
|||||||||||||||||||||||||||||||||||
1 LRSCQGYKQ CNPRPKNLDV GGN KDGGSYDLHRGQLWDGWEG 40






Sequence name: / tmp / tt3yfXIUKV / YxSTFWr66h: SUL1_HUMAN

Sequence documentation:

Alignment of: Z21368_PEA_1_P5 x SUL1_HUMAN ..

Alignment segment 1/1:

Quality: 7878.00 Escore: 0
Matching length: 791 Total length: 871
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 90.82 Total Percent Identity: 90.82
Gaps: 1

Alignment:
....
1 MKYSCCALVLALGLGELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50
||||||||||||||||||||||||||||||||||||||||
1 MKYSCCALVLALGLGELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50
....
51 DDQDVEL ....................................... 57
||||||||
51 DDQDVELGSLQVMNKTRKIMEHGGAGTFINAFVTTPMCCPSRSSMLTGKYV 100
....
58 ...................................... AFFGKYLNEYNGS 70
||||||||||||
101 HNHNVYTNNENC SSP SW QAM HEPRTF AVYLNNTGYRTAFFGKYLNEYNGS 150
....
71 YIPPGWREWLGLIKNSRFYNYTVCRNGIKE KHGFDYAKDYFTDLITNESI 120
||||||||||||||||||||||||||||||||||||||||
151 YIPPGWREWLGLIKNSRFYNYTVCRNGIKE KHGFDYAKDYFTDLITNESI 200
....
121 NYFKMSKRMMYPHRPVMMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYN 170
||||||||||||||||||||||||||||||||||||||||
201 NYFKMSKRMMYPHRPVMMMVISHAAPHGPEDSAPQFSKLYPNA SQIPTSYN 250
....
171 YAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNML 220
||||||||||||||||||||||||||||||||||||||||
251 YAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNML 300
....
221 VETGELENTYII YTADHGYHIGQFGLVKGKSMPYDFDIRVPFIRGPSVE 270
||||||||||||||||||||||||||||||||||||||||
301 VETGELENTYII YTADHGYHIGQFGLVKGKSMPYDFDIRVPFIRGPSVE 350
....
271 PGSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRT 320
||||||||||||||||||||||||||||||||||||||||
351 PGSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRT 400
....
321 NKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLPKYERVKELCQQARY 370
||||||||||||||||||||||||||||||||||||||||
401 NKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLPKYERVKELCQQARY 450
....
371 QTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYARGFHDK 420
||||||||||||||||||||||||||||||||||||||||
451 QTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYARGFHDK 500
....
421 DKECSCRSGYRASRSQRKSMQRQFLRNQGTPKYKPRFVHTRQTRSLSVEF 470
||||||||||||||||||||||||||||||||||||||||
501 DKECSCRESGYRASRSQRKSMQRQFLRNQGTPKYKPRFVHTRQTRSLSVEF 550
....
471 EGEIYDINLEEEEELQ VLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLA 520
||||||||||||||||||||||||||||||||||||||||
551 EGEIYDINLEEEEEL QVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLA 600
....
521 DSSNAVGPPTTVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEI 570
||||||||||||||||||||||||||||||||||||||||
601 DSSNAVGPPTTVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEI 650
....
571 EALQDKIKNLREVRGHLKRRK PEECSCSKQS YYNKEKGVKKQEKLKSHLH 620
||||||||||||||||||||||||||||||||||||||||
651 EALQDKIKNLREVRGHLKRRK PEECSCSKQS YYNKEKGVKKQEKLKSHLH 700
....
621 PFKEAAQEVDSKLQLFKENNRRRKKERKEKRQRKGEECSLPGLTCFTHD 670
||||||||||||||||||||||||||||||||||||||||
701 PFKEAAQEVDSKLQLFKENNRRRKKERKEKRQRKGEECSLPGLTCFTHD 750
....
671 NNHWQTAPFWNLGSFCACTSSNNNTYWCLRTVNETHNFLFCEFATGFLEY 720
||||||||||||||||||||||||||||||||||||||||
751 NNHWQTAPFWNLGSFCACTSSNNNTYWCLRTVNETHNFLFCEFATGFLEY 800
....
721 FDMNTDPYQLTNTVHTVERGILNQLHVLMELRSCQGYKQCNPRPKNLDV 770
||||||||||||||||||||||||||||||||||||||||
801 FDMNTDPYQLTNTVHTVERGILNQLHVLMELRSCQGYKQCNPRPKNLDV 850
.
771 GNKDGGSYDLHRGQLWDGWEG 791
||||||||||||||||||||
851 GNKDGGSYDLHRGQLWDGWEG 871






Sequence name: / tmp / AVAZGWHuF0 / RzHFOnHIsT: SUL1_HUMAN

Sequence documentation:

Alignment of: Z21368_PEA_1_P15 x SUL1_HUMAN ..

Alignment segment 1/1:

Quality: 4174.00 Escore: 0
Matching length: 416 Total length: 416
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MKYSCCALVLALGLGELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50
||||||||||||||||||||||||||||||||||||||||
1 MKYSCCALVLALGLGELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50
....
51 DDQDVELGSLQVMNKTRKIMEHGGAGTFINAFVTTPMCCPSRSSMLTGKYV 100
||||||||||||||||||||||||||||||||||||||||
51 DDQDVELGSLQVMNKTRKIMEHGGAGTFINAFVTTPMCCPSRSSMLTGKYV 100
....
101 HNHNVYTNNENC SSP SW QAM HEPRTF AVYLNNTGYRTAFFGKYLNEYNGS 150
||||||||||||||||||||||||||||||||||||||||
101 HNHNVYTNNENC SSP SW QAM HEPRTF AVYLNNTGYRTAFFGKYLNEYNGS 150
....
151 YIPPGWREWLGLIKNSRFYNYTVCRNGIKE KHGFDYAKDYFTDLITNESI 200
||||||||||||||||||||||||||||||||||||||||
151 YIPPGWREWLGLIKNSRFYNYTVCRNGIKE KHGFDYAKDYFTDLITNESI 200
....
201 NYFKMSKRMMYPHRPVMMMVISHAAPHGPEDSAPQFSKLYPNA SQIPTSYN 250
||||||||||||||||||||||||||||||||||||||||
201 NYFKMSKRMMYPHRPVMMMVISHAAPHGPEDSAPQFSKLYPNA SQIPTSYN 250
....
251 YAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNML 300
||||||||||||||||||||||||||||||||||||||||
251 YAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNML 300
....
301 VETGELENTYII YTADHGYHIGQFGLVKGKSMPYDFDIRVPFIRGPSVE 350
||||||||||||||||||||||||||||||||||||||||
301 VETGELENTYII YTADHGYHIGQFGLVKGKSMPYDFDIRVPFIRGPSVE 350
....
351 PGSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRT 400
||||||||||||||||||||||||||||||||||||||||
351 PGSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRT 400
.
401 NKKAKIWRDTFLVERG 416
||||||||||||||||
401 NKKAKIWRDTFLVERG 416






Sequence name: / tmp / JhwgRdKqmt / kqSmjxkWWk: SUL1_HUMAN

Sequence documentation:

Alignment of: Z21368_PEA_1_P16 x SUL1_HUMAN ..

Alignment segment 1/1:

Quality: 3985.00 Escore: 0
Matching length: 397 Total length: 397
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MKYSCCALVLALGLGELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50
||||||||||||||||||||||||||||||||||||||||
1 MKYSCCALVLALGLGELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50
....
51 DDQDVELGSLQVMNKTRKIMEHGGAGTFINAFVTTPMCCPSRSSMLTGKYV 100
||||||||||||||||||||||||||||||||||||||||
51 DDQDVELGSLQVMNKTRKIMEHGGAGTFINAFVTTPMCCPSRSSMLTGKYV 100
....
101 HNHNVYTNNENC SSP SW QAM HEPRTF AVYLNNTGYRTAFFGKYLNEYNGS 150
||||||||||||||||||||||||||||||||||||||||
101 HNHNVYTNNENC SSP SW QAM HEPRTF AVYLNNTGYRTAFFGKYLNEYNGS 150
....
151 YIPPGWREWLGLIKNSRFYNYTVCRNGIKE KHGFDYAKDYFTDLITNESI 200
||||||||||||||||||||||||||||||||||||||||
151 YIPPGWREWLGLIKNSRFYNYTVCRNGIKE KHGFDYAKDYFTDLITNESI 200
....
201 NYFKMSKRMMYPHRPVMMMVISHAAPHGPEDSAPQFSKLYPNA SQIPTSYN 250
||||||||||||||||||||||||||||||||||||||||
201 NYFKMSKRMMYPHRPVMMMVISHAAPHGPEDSAPQFSKLYPNA SQIPTSYN 250
....
251 YAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNML 300
||||||||||||||||||||||||||||||||||||||||
251 YAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNML 300
....
301 VETGELENTYII YTADHGYHIGQFGLVKGKSMPYDFDIRVPFIRGPSVE 350
||||||||||||||||||||||||||||||||||||||||
301 VETGELENTYII YTADHGYHIGQFGLVKGKSMPYDFDIRVPFIRGPSVE 350
....
351 PGSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEPPGNR 397
|||||||||||||||||||||||||||||||||||||||
351 PGSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEPPGNR 397






Sequence name: / tmp / GPlnIw3BOg / zXFdxqG4ow: SUL1_HUMAN

Sequence documentation:

Alignment of: Z21368_PEA_1_P22 x SUL1_HUMAN ..

Alignment segment 1/1:

Quality: 1897.00 Escore: 0
Matching length: 188 Total length: 188
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MKYSCCALVLALGLGELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50
||||||||||||||||||||||||||||||||||||||||
1 MKYSCCALVLALGLGELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50
....
51 DDQDVELGSLQVMNKTRKIMEHGGAGTFINAFVTTPMCCPSRSSMLTGKYV 100
||||||||||||||||||||||||||||||||||||||||
51 DDQDVELGSLQVMNKTRKIMEHGGAGTFINAFVTTPMCCPSRSSMLTGKYV 100
....
101 HNHNVYTNNENC SSP SW QAM HEPRTF AVYLNNTGYRTAFFGKYLNEYNGS 150
||||||||||||||||||||||||||||||||||||||||
101 HNHNVYTNNENC SSP SW QAM HEPRTF AVYLNNTGYRTAFFGKYLNEYNGS 150
....
151 YIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAK 188
|||||||||||||||||||||||||||||||||||
151 YIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAK 188


Sequence name: / tmp / oji5Fs74fB / 8xeB9KrGjp: Q7Z2W2

Sequence documentation:

Alignment of: Z21368_PEA_1_P23 x Q7Z2W2 ..

Alignment segment 1/1:

Quality: 1368.00 Escore: 0.000511
Matching length: 137 Total length: 137
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MKYSCCALVLALGLGELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50
||||||||||||||||||||||||||||||||||||||||
1 MKYSCCALVLALGLGELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50
....
51 DDQDVELGSLQVMNKTRKIMEHGGAGTFINAFVTTPMCCPSRSSMLTGKYV 100
||||||||||||||||||||||||||||||||||||||||
51 DDQDVELGSLQVMNKTRKIMEHGGAGTFINAFVTTPMCCPSRSSMLTGKYV 100
....
101 HNHNVYTNNENC SSP SW QAM HEPRTFAVYLNNTGYRT 137
||||||||||||||||||||||||||||||||||
101 HNHNVYTNNENC SSP SW QAM HEPRTFAVYLNNTGYRT 137






Sequence name: / tmp / oji5Fs74fB / 8xeB9KrGjp: SUL1_HUMAN

Sequence documentation:

Alignment of: Z21368_PEA_1_P23 x SUL1_HUMAN ..

Alignment segment 1/1:

Quality: 1368.00 Escore: 0.000511
Matching length: 137 Total length: 137
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MKYSCCALVLALGLGELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50
||||||||||||||||||||||||||||||||||||||||
1 MKYSCCALVLALGLGELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50
....
51 DDQDVELGSLQVMNKTRKIMEHGGAGTFINAFVTTPMCCPSRSSMLTGKYV 100
||||||||||||||||||||||||||||||||||||||||
51 DDQDVELGSLQVMNKTRKIMEHGGAGTFINAFVTTPMCCPSRSSMLTGKYV 100
....
101 HNHNVYTNNENC SSP SW QAM HEPRTFAVYLNNTGYRT 137
||||||||||||||||||||||||||||||||||
101 HNHNVYTNNENC SSP SW QAM HEPRTFAVYLNNTGYRT 137

Expression of SUL1_HUMAN extracellular sulfatase Sulf-1 Z21 368 transcript detectable by an amplicon as shown in sequence name Z21 368 jun c17 -21 in normal and cancerous lung tissue junc 17-21 segment, Z21 368 jun c17 -21 amplicon (SEQ ID NO 1642), and Z21 368 junc17 The expression of SUL1_HUMAN-extracellular sulfatase Sulf-1 transcripts detectable by -21F (SEQ ID NO: 1640), Z21368 junc 17-21 R (SEQ ID NO: 1641) primers was measured by real-time PCR. In parallel, four housekeeping genes-PBGD (GenBank Accession No. BC019323, Amplicon – PBGD-Amplicon, SEQ ID No. 334), HPRT1 (GenBank Accession No. NM_000194, Amplicon – HPRT1- Amplicons, SEQ ID NO: 1297), Ubiquitin (GenBank Accession No. BC000449, Amplicon – Ubiquitin-Amplicon, SEQ ID NO: 328), and SDHA (GenBank Accession No. NM_004168, Amplicon – SDHA-Amplifier Recon SEQ ID NO: 331) was similarly measured. For each RT sample, the expression of the amplicon was normalized to the geometric mean of the housekeeping gene dose. The normalized amount of each RT sample is the middle of the normal postmortem (PM) sample (sample numbers 47-50, 90-93, 96-99, Table 2, "tissue sample in test panel", above) Divide by the value to obtain the magnification of the upregulation of each sample relative to the median of normal PM samples.

  FIG. 14 is a histogram showing over expression of the SUL1_HUMAN-extracellular sulfatase Sulf-1 transcript in cancerous lung samples compared to normal samples. Values represent the average of duplicate experiments. Error bars indicate the obtained minimum and maximum values. As apparent from FIG. 14, the expression of SUL1_HUMAN-extracellular sulfatase Sulf-1 transcript detectable by the above amplicon in a cancer sample is a non-cancerous sample (sample numbers 47-50, 90-93, 96- 99, Table 2, "Tissue samples in test panel" was significantly higher. Clearly, 10 out of 15 adenocarcinoma samples, 16 out of 16 squamous cell carcinoma samples, 0 out of 4 large cell carcinoma samples, 0 out of 8 small cell carcinoma samples Over expression of at least 5 fold was found.

  The 5-fold overexpression threshold was found to be different between cancer and normal samples, checked by Fisher's exact test, P value is 3.56E-04 for adenocarcinoma, squamous cell carcinoma in adenocarcinoma And 9.66E-03. The above values indicate that the results are statistically significant.

  Primer pairs are also optionally and preferably included within the scope of the present invention, for example, in the above experiments the following primers were used only as non-limiting examples of suitable primer pairs: Z21368junc17-21F forward primer and Z21368 junc 17-21 R reverse primer.

  The present invention also preferably includes any amplicon obtained by use of any suitable primer pair (e.g. in the above experiments) and obtained the following amplicons only as a non-limiting illustration of a suitable amplicon : Z21368 junc 17-21.

Forward primer (SEQ ID NO: 1640): GGACGGATACAGCAGGAACG
Reverse Amplicon (SEQ ID NO: 1641): TATTTTCCAAAAAGGGCCAGCT
Amplicon (SEQ ID NO: 1642): GGACGGATACAGCAGGAACAAAAAACATCCGACCCAACATTATTCTTGTGCTTACCGATGATCAAGATGTGGAGCTGGCCTTTTTTGAAAATA

Expression of SUL1_HUMAN extracellular sulfatase Sulf-1 Sulfate transcript detectable by an amplicon as shown in sequence name Z21368junc17-21 in different normal tissues Z21368junc17-21 amplicon (SEQ ID NO: 1642), Z21368 junc17-21F (SEQ ID NO: 1640), and The expression of SUL1_HUMAN extracellular sulfatase Sulf-1 transcripts detectable by Z21368 junc17-21R (SEQ ID NO: 1641) was measured by real time PCR. In parallel, four housekeeping genes-RPL19 (GenBank Accession No. NM_000981, RPL19 amplicon, SEQ ID No. 1630), TATA box (GenBank Accession No. NM_003194, TATA amplicon, SEQ ID No. 1633), ubiquitin (GenBank Accession No. BC000449, amplicon – ubiquitin amplicon, SEQ ID NO: 328), and SDHA (GenBank accession number NM_004168; amplicon >#8211; SDHA-amplicon, SEQ ID NO: 331) were similarly measured. For each RT sample, the expression of the amplicon was normalized to the geometric mean of the housekeeping gene dose. Divide the normalized amount of each RT sample by the median of the amount of breast samples (Sample Nos. 33-35 above, Table 3, "Tissue samples in normal panel"), to each sample relative to the median of breast samples The relative expression value of was obtained.

Forward primer (SEQ ID NO: 1640): GGACGGATACAGCAGGAACG
Reverse Amplicon (SEQ ID NO: 1641): TATTTTCCAAAAAGGGCCAGCT
Amplicon (SEQ ID NO: 1642): GGACGGATACAGCAGGAACAAAAAACATCCGACCCAACATTATTCTTGTGCTTACCGATGATCAAGATGTGGAGCTGGCCTTTTTTGAAAATA

  The results are shown in FIG. 15, which shows the expression of extracellular sulfatase Sulf-1 Z21368 transcripts detectable by the amplicon shown in the sequence name Z21368 junc17-21 in different normal tissues.

Expression of SUL1_HUMAN-extracellular sulfatase Sulf-1 Z21 368 transcript detectable by an amplicon shown in sequence name Z21 368 seg 39 in normal and cancerous lung tissue seg39, Z21 368 seg 39 amplicon (SEQ ID NO: 1645), and primer Z21 368 seg 39 F (SEQ ID NO: 1643) And the expression of SUL1_HUMAN-extracellular sulfatase Sulf-1 transcript detectable by Z21368 seg39R (SEQ ID NO: 1644) was measured by real time PCR. In parallel, four housekeeping genes-PBGD (GenBank Accession No. BC019323, Amplicon – PBGD-Amplicon, SEQ ID No. 334), HPRT1 (GenBank Accession No. NM_000194, Amplicon – HPRT1- Amplicons, SEQ ID NO: 1297), Ubiquitin (GenBank Accession No. BC000449, Amplicon – Ubiquitin-Amplicon SEQ ID NO: 328), and SDHA (GenBank Accession No. NM_004168, Amplicon – SDHA-Amplicon SEQ ID NO: 331) was similarly measured. For each RT sample, the expression of the amplicon was normalized to the geometric mean of the housekeeping gene dose. The normalized volume of each RT sample is the median volume of normal postmortem (PM) samples (sample numbers 47-50, 90-93, 96-99, Table 2, "tissue samples in the test panel") Divided to obtain the magnification of upregulation of each sample relative to the median of normal PM samples.

  FIG. 16 is a histogram showing over expression of the SUL1_HUMAN-extracellular sulfatase Sulf-1 transcript in cancerous lung samples compared to normal samples. Values represent the average of duplicate experiments. Error bars indicate the obtained minimum and maximum values. As apparent from FIG. 16, the expression of SUL1_HUMAN-extracellular sulfatase Sulf-1 transcript detectable by the above amplicon in a cancer sample is a non-cancerous sample (sample numbers 47-50, 90-93, 96- 99, Table 2, "Tissue samples in test panel" was significantly higher. Apparently, at least 5-fold overexpression was found in 8 out of 15 adenocarcinoma samples, 5 out of 16 squamous cell carcinoma samples, and 1 out of 4 large cell carcinoma samples. It was done.

  Statistical analysis was applied to verify the significance of these results, as described below.

  P value for differences in expression levels of SUL1_HUMAN-extracellular sulfatase Sulf-1 transcripts detectable by the above amplicon in lung cancer samples versus normal tissue samples, by T-test, 2.17E-04 in adenocarcinoma, squamous epithelium It was determined to be 9.94E-03 for cell carcinoma and 2.17E-01 for large cell carcinoma.

  The 5-fold overexpression threshold was found to be different between cancer and normal samples, and P value was checked by Fisher's exact test, 1.74E-02 for adenocarcinoma, squamous cell carcinoma Of the large cell carcinoma and 4.33 E-01. The above values indicate that the results are statistically significant.

  Primer pairs are also optionally and preferably included within the scope of the present invention, for example, in the above experiments the following primers were used only as non-limiting examples of suitable primer pairs: Z21368 seg39 F forward primer and Z21 368 seg 39 R reverse Direction primer.

  The present invention also preferably includes any amplicon obtained by use of any suitable primer pair (e.g. in the above experiments) and obtained the following amplicons only as a non-limiting illustration of a suitable amplicon : Z21368 seg 39.

Primer:
Forward primer Z21368seg39F (SEQ ID NO: 1643): GTTGCATTTCTCAGTGCTGGTTT
Reverse primer Z21368seg39R (SEQ ID NO: 1644): AGGGTGCCGGGTGAGG
Amplicon Z21368 seg 39 (SEQ ID NO: 1645): GTTGCATTTCTCAGTGCTGGTTTCTAATCAGACCAGTGGGATTGAGTTTCTACTACATCCTCCCCCACGTTCTTCTTAAGCTGGCTCCAAAGCCTCACCCGGCACCCT

Expression of SUL1_HUMAN-extracellular sulfatase Sulf-1 Z21368 transcript detectable by an amplicon as shown in sequence name Z21368seg39 in different normal tissues Z21368seg39 amplicon (SEQ ID NO: 1645), Z21368 seg39F (SEQ ID NO: 1643), Z21368 seg39R (SEQ ID NO: 1644) The expression of SUL1_HUMAN-extracellular sulfatase Sulf-1 transcripts detectable by was measured by real-time PCR. In parallel, four housekeeping genes-[RPL19 (GenBank Accession No. NM_000981, RPL19 Amplicon, SEQ ID No. 1630), TATA box (GenBank Accession No. NM_003194, TATA Amplicon, SEQ ID No. 1633), UBC (GenBank Accession No. BC000449, amplicon – ubiquitin amplicon, SEQ ID NO: 328), and SDHA (GenBank Accession No. NM_004168, amplicon >#8211; SDHA amplicon, SEQ ID NO: 331) were similarly measured. For each RT sample, the expression of the amplicon was normalized to the geometric mean of the housekeeping gene dose. The normalized amount of each RT sample was divided by the median of the amounts of breast samples (Sample Nos. 33-35 above, Table 3) to obtain relative expression values of each sample relative to the median of breast samples.

Forward primer Z21368seg39F (SEQ ID NO: 1643): GTTGCATTTCTCAGTGCTGGTTT
Reverse primer Z21368seg39R (SEQ ID NO: 1644): AGGGTGCCGGGTGAGG
Amplicon Z 21368 seg 39 (SEQ ID NO: 1645): GTTGCATTTCTCAGTGCTGGTTTCTAATCAGACCAGTGGGATTGAGTTTCTACTACATCCTCCCCCACGTTCTTCTTAAGCTGCCTCCAAGCCTCACCCGGCACCCT

  The results are shown in FIG. 17, which shows the expression of SUL1_HUMAN-extracellular sulfatase Sulf-1 Z21368 transcripts detectable by the amplicon shown in the sequence name Z21368 seg39 in different normal tissues.

  PBGD-amplicon (SEQ ID NO: 334), HPRT1-amplicon (SEQ ID NO: 1297), ubiquitin-amplicon (SEQ ID NO: 328), SDHA-amplicon (SEQ ID NO: 331), PBGD-amplicon (SEQ ID NO: 334) HPRT1- amplicon (SEQ ID NO: 1297), ubiquitin amplicon (SEQ ID NO: 328), SDHA-amplicon (SEQ ID NO: 331), RPL19 amplicon (SEQ ID NO: 1630), TATA amplicon (SEQ ID NO: 1633), ubiquitin- Amplicon (SEQ ID NO: 328), SDHA-Amplicon (SEQ ID NO: 331)

Description of cluster HUMGRP5E The cluster HUMGRP5E is characterized by two transcripts and five segments of interest, the names of which are shown in Tables 160 and 161 respectively, and the sequence itself is shown at the end of the application. Selected protein variants are shown in Table 162.

  These sequences are mutations of the known protein gastrin-releasing peptide precursor (SwissProt accession identifier GRP_HUMAN, synonym: GRP, GRP-10) (SEQ ID NO: 1421), which is a known protein, previously known herein as a protein It is a type.

  Gastrin releasing peptides are known or considered to have the following functions: to stimulate gastrin release and other gut hormones. The sequence of the protein gastrin releasing peptide precursor is shown at the end of the application as "gastrin releasing peptide precursor amino acid sequence". Known polymorphisms of this sequence are shown in Table 163.

  Localization of the protein gastrin releasing peptide is considered secretion.

  The previously known proteins also have the following indications and / or potential therapeutic applications: Type II diabetes. Clinical / therapeutic applications in humans (e.g. as targets for antibodies or small molecules and / or as direct therapy) are being investigated and available information related to these investigations is: Potential pharmaceutically relevant or therapeutically relevant activities of previously known proteins are: bombesin antagonists, insulinotropin agonists. The therapeutic role of proteins displayed by clusters is expected. Drug database that can or can be used to apply this protein or part thereof for potential treatment (appetite / obesity suppressant, hormone release, anti-cancer, respiratory, anti-diabetic) Clusters were assigned to this area as the information exists in public databases (eg, above).

  The following GO annotation applies to previously known proteins. The following annotations have been found: in signal processing that is related to biological processes, neuropeptide signaling, growth factors that are related to molecular function, and in annotations related to cellular components. There is a secretion.

  GO assignments can be made at one or more http: // www. expasy. SwissProt / TremBl Protein knowledgebase available from ch / sprot / or http: // www. ncbi. nlm. nih. Depends on Locuslink available from gov / projects / LocusLink /.

  As mentioned above, cluster HUMGRP5E is characterized by the two transcripts listed in Table 160 above. These transcripts encode proteins which are variants of the protein gastrin releasing peptide precursor. A description of each mutein of the invention is provided herein.

  The mutein HUMGRP5E_P4 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript HUMGRP5E_T4. An alignment to a known protein (gastrin releasing peptide precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report comparison of HUMGRP5E_P4 with GRP_HUMAN 1. MRGSELPLVLALGLCLAPGRAPGPAPGAGTGTVLTK MYPRGHNHWAGHMGKKSTGESSSVSERGSLLKQQLREY ARLEGLEKENQQPQALQQP QLSQDSS FK FK 対 応 対 応 対 応 対 応 GRP MR _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 7 HUMG comprising a second amino acid sequence that is at least 90% homologous to the corresponding GSQREGRNPQLNQQ, wherein said first and second amino acid sequences are adjacent and in sequential order Isolated chimeric polypeptide encoding P5E_P4.

  2. Length “n” (wherein n is at least about 10 amino acids long, optionally at least about 20 amino acids long, preferably at least about 30 amino acids long, more preferably at least about 40 amino acids long, most preferably at least about 50 amino acids in length, at least two amino acids comprising KG, starting from any of the following structures: amino acid numbers 127-x to 127, amino acid numbers 128 + ((n-2) -x) (formula An isolated chimeric polypeptide encoding an edge portion of HUMGRP5E_P4, comprising a polypeptide, having a sequence terminating in: x) varying from 0 to n-2).

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein HUMGRP5E_P4 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows SNPs as shown in Table 164) It indicates whether it is known and the presence of a known SNP in the mutant protein HUMGRP5E_P4 sequence supports the deduced sequence of this mutant protein according to the invention).

  The mutein HUMGRP5E_P4 is encoded by the following transcript: HUMGRP5E_T4 (sequences shown at the end of the application). The coding portion of the transcript HUMGRP5E_T4 is shown in bold, starting from position 622 and ending at position 1044. The transcript also has the following SNPs listed in Table 165 (indicating its position on the nucleotide sequence and listing another nucleic acid, the last column indicating whether the SNP is known, the mutein HUMGRP5E_P4 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein HUMGRP5E_P5 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript HUMGRP5E_T5. An alignment to a known protein (gastrin releasing peptide precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report comparison of HUMGRP5E_P5 with GRP_HUMAN 1. MHR GEL PLVLLULCLCLAPRAPGPRPGVLEGELLHCLHCLIPRAPGLPLPAGPGIPLEGCLIPTVLHCLIVCLVCLVCLVCLVCLVCLVCLVCLVCLVCLVCLVCLVCLVCLVCLVCLVCLVCLVCLVCLVCLVCLVCLVCLVCLVCLVCLVCLVCLVCLVCLVCLVCLVCLVCLVCLVCLVCLVCLVCLVCLVSPCLVCLV LYCLIPJHSPLJCLVJCLV LY, JHJHQHQHJLQQN. At least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous And a acid sequence, wherein the first and second amino acid distribution is contiguous, and in sequential order, the isolated chimeric polypeptide coding HUMGRP5E_P5.

  2. A HUMGRP5E_P5 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence DSLLQVLNVKEGTPS in HUMGRP5E_P5 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein HUMGRP5E_P5 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing the other amino acids, and listing the other amino acids, and the last column shows the SNPs), as shown in Table 166 It indicates whether it is known and the presence of a known SNP in the mutant protein HUMGRP5E_P5 sequence supports the deduced sequence of this mutant protein according to the invention).

  The mutein HUMGRP5E_P5 is encoded by the following transcript: HUMGRP5E_T5 (sequences shown at the end of the application). The coding part of the transcript HUMGRP5E_T5 is shown in bold, starting from position 622 and ending at position 1047. The transcript also has the following SNPs listed in Table 167 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, the mutein HUMGRP5E_P5 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  As mentioned above, cluster HUMGRP5E is characterized by the five segments listed in Table 161 above, the sequences of which are shown at the end of the application. These segments are part of the nucleic acid sequence, which are of particular interest and are individually described herein. A description of each segment of the invention is provided herein.

  The segment cluster HUMGRP5E_node_0 of the present invention is supported by 21 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMGRP5E_T4 and HUMGRP5E_T5. Table 168 below lists the start and end positions of this segment on each transcript.

  The segment cluster HUMGRP5E_node_2 of the present invention is supported by 27 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMGRP5E_T4 and HUMGRP5E_T5. Table 169 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMGRP5E_node_8 of the present invention is supported by 26 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMGRP5E_T4 and HUMGRP5E_T5. Table 170 below lists the start and end positions of this segment on each transcript.

  According to an optional embodiment of the present invention, there is also provided a short segment associated with the above cluster. These segments are up to about 120 bp in length and are therefore included in the individual descriptions.

  The segment cluster HUMGRP5E_node_3 according to the invention can be found in the following transcript: HUMGRP5E_T4 and HUMGRP5E_T5. Table 171 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMGRP5E_node_7 according to the invention can be found in the following transcript: HUMGRP5E_T5. Table 172 below describes the start and end positions of this segment on each transcript.

  Microarray (chip) data of this gene is also available, as follows. As described above, with respect to the clusters themselves, different oligonucleotides were tested for differential expression in different disease states, in particular cancer. The following oligonucleotides were found to reach this segment (for lung cancer) (shown in Table 173).

Mutated protein alignment against previously known proteins:
Sequence name: / tmp / 412zs2mwyT / B0wjOUAX0d: GRP_HUMAN

Sequence documentation:

Alignment of: HUMGRP5E_P4 x GRP_HUMAN ..

Alignment segment 1/1:

Quality: 1291.00 Escore: 0
Matching length: 141 Total length: 148
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 95.27 Total Percent Identity: 95.27
Gaps: 1

Alignment:
....
1 MRGSELPLVLLALVLCLAPGRAVPLPAGGGTVLTK MYPRGNHAWAVGHLM 50
||||||||||||||||||||||||||||||||||||||||
1 MRGSELPLVLLALVLCLAPGRAVPLPAGGGTVLTK MYPRGNHAWAVGHLM 50
....
51 GKKSTGESSSVSERGSLKQQLREYIRWEEAARNLLGLEEAKENRNHQPPQ 100
||||||||||||||||||||||||||||||||||||||||
51 GKKSTGESSSVSERGSLKQQLREYIRWEEAARNLLGLEEAKENRNHQPPQ 100
....
101 PKALGNQQPSWDSEDSSNFKDVGSKGGK ....... GSQREGRNPQLNQQ 141
||||||||||||||||||||||||||||||||||
101 PKALGNQQPSWDSEDSSNFKDVGSKGGKVGRLSAPGSQREGRNPQLNQQ 148






Sequence name: / tmp / 1me9ldnvfv / KbP5io8PtU: GRP_HUMAN

Sequence documentation:

Alignment of: HUMGRP5E_P5 x GRP_HUMAN ..

Alignment segment 1/1:

Quality: 1248.00 Escore: 0
Matching length: 127 Total length: 127
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MRGSELPLVLLALVLCLAPGRAVPLPAGGGTVLTK MYPRGNHAWAVGHLM 50
||||||||||||||||||||||||||||||||||||||||
1 MRGSELPLVLLALVLCLAPGRAVPLPAGGGTVLTK MYPRGNHAWAVGHLM 50
....
51 GKKSTGESSSVSERGSLKQQLREYIRWEEAARNLLGLEEAKENRNHQPPQ 100
||||||||||||||||||||||||||||||||||||||||
51 GKKSTGESSSVSERGSLKQQLREYIRWEEAARNLLGLEEAKENRNHQPPQ 100
.
101 PKALGNQQPSWDSEDSSNFKDVSKSGK 127
|||||||||||||||||||||||||
101 PKALGNQQPSWDSEDSSNFKDVSKSGK 127

Expression of GRP_HUMAN-gastrin releasing peptide (HUMGRP5E) transcript detectable by an amplicon as shown in sequence name HUMGRP5Ejunc3-7 in normal and cancerous lung tissue HUMGRP5Ejunc3-7 amplicon (SEQ ID NO: 1648), and HUMGRP5Ejunc3-7F (sequence No. 1646) and HUMGRP5 Ejunc3-7R (SEQ ID NO: 1647) The expression of GRP_HUMAN-gastrin releasing peptide transcripts detectable by primers was measured by real-time PCR. In parallel, four housekeeping genes-PBGD (GenBank Accession No. BC019323, Amplicon – PBGD-Amplicon, SEQ ID No. 334), HPRT1 (GenBank Accession No. NM_000194, Amplicon – HPRT1- Amplicons, SEQ ID NO: 1297), Ubiquitin (GenBank Accession No. BC000449, Amplicon – Ubiquitin-Amplicon SEQ ID NO: 328), and SDHA (GenBank Accession No. NM_004168, Amplicon – SDHA-Amplicon SEQ ID NO: 331) was similarly measured. For each RT sample, the expression of the amplicon was normalized to the geometric mean of the housekeeping gene dose. The normalized amount of each RT sample is the median amount of normal postmortem (PM) samples (sample numbers 47-50, 90-93, 96-99, Table 2, "tissue samples in test samples") Divided to obtain the magnification of upregulation of each sample relative to the median of normal PM samples.

  FIG. 16 is a histogram showing over expression of the GRP_HUMAN-gastrin releasing peptide transcript in several cancerous lung samples compared to normal samples. As apparent from FIG. 19, the expression of GRP_HUMAN-gastrin releasing peptide transcripts detectable by the above amplicon in several cancer samples is a non-cancerous sample (sample numbers 47 to 50, 90 to 93, 96 to 99, Table 2, "Tissue samples in test samples" was significantly higher. Clearly, at least 10-fold overexpression was found in 2 out of 15 adenocarcinoma samples and 7 out of 8 small cell carcinoma samples.

  Primer pairs are also optionally and preferably included within the scope of the present invention, for example, in the above experiments the following primers were used only as non-limiting examples of suitable primer pairs: HUMGRP5 Ejunc3-7F forward primer and HUMGRP5 Ejunc3-7R reverse primer.

  The present invention also preferably includes any amplicon obtained by use of any suitable primer pair (e.g. in the above experiments) and obtained the following amplicons only as a non-limiting illustration of a suitable amplicon : HUMGRP5 Ejunc 3-7.

HUMGRP5 Ejunc 3-7F (SEQ ID NO: 1646)
ACCAGGCACCTCCAACCCA
HUMGRP5 Ejunc 3-7R (SEQ ID NO: 1647)
CTGGAGCAGAGAGTCTTTGCCT
HUMGRP5 Ejunc 3-7 (SEQ ID NO: 1648)
ACCAGCC ACCTCA ACCCA AGGCCCTGGGCAATCAGCAGCCCTTCGTGGGATTCAGAGGATAGCAGCAACTTCAAAGATGTAGGTTCAAAAGGCAAAGACTCTCGTCC G

Expression of GRP_HUMAN-gastrin releasing peptide (HUMGRP5E) transcript detectable by the amplicon shown in the sequence name HUMGRP5Ejunc3-7 in different normal tissues HUMGRP5Ejunc3-7 amplicon (SEQ ID NO: 1648), as well as HUMGRP5 Ejunc3-7F (SEQ ID NO: 1646) And expression of GRP_HUMAN-gastrin releasing peptide transcripts detectable by HUMGRP5Ejunc3-7R (SEQ ID NO: 1647) was measured by real time PCR. In parallel, four housekeeping genes-RPL19 (GenBank Accession No. NM_000981, RPL19 amplicon, SEQ ID No. 1630), TATA box (GenBank Accession No. NM_003194, TATA amplicon, SEQ ID No. 1633), ubiquitin (GenBank Accession No. BC000449, amplicon – ubiquitin-amplicon, SEQ ID NO: 328), and SDHA (GenBank accession number NM_004168, amplicon – SDHA-amplicon, SEQ ID NO: 331) were similarly measured. For each RT sample, the expression of the amplicon was normalized to the geometric mean of the housekeeping gene dose. Divide the normalized amount of each RT sample by the median of the amount of breast samples (Sample Nos. 33-35 above, Table 3, "Tissue Samples in Normal Panel") to obtain each sample relative to the median of breast samples Relative expression values were obtained.

HUMGRP5 Ejunc 3-7F (SEQ ID NO: 1646)
ACCAGGCACCTCCAACCCA
HUMGRP5 Ejunc 3-7R (SEQ ID NO: 1647)
CTGGAGCAGAGAGTCTTTGCCT
HUMGRP5 Ejunc 3-7 (SEQ ID NO: 1648)
ACCAGCC ACCTCA ACCCA AGGCCCTGGGCAATCAGCAGCCCTTCGTGGGATTCAGAGGATAGCAGCAACTTCAAAGATGTAGGTTCAAAAGGCAAAGACTCTCGTCC G

  The results are shown in FIG. 20, which shows the expression transcripts of GRP_HUMAN-gastrin releasing peptide (HUMGRP5E) transcript detectable by an amplicon as shown in the sequence name HUMGRP5Ejunc3-7 in different normal tissues.

Description of Cluster D56406 Cluster D56406 features 3 transcripts of interest and 10 segments, the names of which are shown in Tables 174 and 175, respectively, and the sequence itself is shown at the end of the application. Selected protein variants are shown in Table 176.

  These sequences are known proteins, previously known herein as proteins known as neurotensin / neuromedin N precursor (including: large neuromedin N) (NmN-125), neuromedin N (NmN) (NN), neurotensin (NT), tail peptide) (SwissProt accession identifier NEUT_HUMAN) (SEQ ID NO: 1422).

  The protein neurotensin / neuromedin N precursor is known or considered to have the following function: Neurotensin may play an endocrine or paracrine role in the regulation of fat metabolism. This causes contraction of smooth muscle. The sequence of the protein neurotensin / neuromedin N precursor “neurotensin / neuromedin N precursor (including: large neuromedin N (NmN-125), neuromedin N (NmN) (NN), neurotensin (NT), tail It is shown at the end of the application as "peptide" amino acid sequence ". The localization of the protein neurotensin / neuromedin N precursor is considered to be secretion (packaging into secretory vesicles).

  The following GO annotation applies to previously known proteins. The following annotations were found: signal transduction that is related to biological processes, signal transduction that is related to molecular functions, neuropeptide hormones that are related to molecular functions, and soluble fractions that are annotated related to cellular components .

  GO assignments can be made at one or more http: // www. expasy. SwissProt / TremBl Protein knowledgebase available from ch / sprot / or http: // www. ncbi. nlm. nih. Depends on Locuslink available from gov / projects / LocusLink /.

  As mentioned above, cluster D56406 is characterized by the three transcripts listed in Table 174 above. These transcripts encode a protein that is a mutated form of neurotensin / neuromedin N precursor. A description of each mutein of the invention is provided herein.

  The mutein D56406_PEA_1_P2 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript D56406_PEA_1_T3. An alignment to a known protein (neurotensin / neuromedin N precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of the comparison between D56406_PEA_1_P2 and NEUT_HUMAN 1. A corresponding MMA GMlQl vmllla fssl ssd sDsL sDs s s corresponding to amino acids 1-120 of NEUT_HUMAN and d56 406 _ PEA _ P2 s s s s s s s s s s s s s s s s s s At least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferred Or a second amino acid sequence that is at least 95% homologous, and a third amino acid sequence that is at least 90% homologous to LIQEDILDTGNDNGNGKEEVIKRKIPYILKRQLYENKPRRPYILKRDSYYY corresponding to amino acids 121 to 170 of NEUT_HUMAN and also to amino acids 152 to 201 of D56406_PEA_1_P2 An isolated chimeric polypeptide encoding D56406_PEA_1_P2, wherein said first, second and third amino acid sequences are in contiguous and sequential order.

  2. An amino acid sequence at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence encoding ARWLTPVIPALWEAETGGSRGQEMETIPANT corresponding to D56406_PEA_1_P2 An isolated polypeptide encoding the edge portion of D56406_PEA_1_P2 comprising.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein D56406_PEA_1_P2 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids and listing the other amino acids, as shown in Table 177), and the last column shows the SNP It is shown whether it is known and the presence of a known SNP in the mutein D56406_PEA_1_P2 sequence supports the putative sequence of this mutein of the invention).

  The mutein D56406_PEA_1_P2 is encoded by the following transcript: D56406_PEA_1_T3 (sequences shown at the end of the application). The code portion of transcript D56406_PEA_1_T3 is shown in bold and starts at position 106 and ends at position 708. The transcript also has the following SNPs listed in Table 178 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein D56406_PEA_1_P2 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein D56406_PEA_1_P5 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript D56406_PEA_1_T6. An alignment to a known protein (neurotensin / neuromedin N precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of the comparison between D56406_PEA_1_P5 and NEUT_HUMAN 1. A first amino acid sequence that is at least 90% homologous to MMAGMKI QL VCMCLLA FSS SWLC corresponding to amino acids 1-23 of NEUT_HUMAN and also to amino acids 1-23 of D56406_PEA_1_P5 and amino acids 24-168 of D56406_PEA_1_P5 corresponding to amino acids 26-170 of NEUT_HUMAN SEEMKALEADLFLTNMHTSKISKAHVPSWKMTLLNVCSLVNLNNSPAEETGEVHEEEL VARRKLPTALDSLEAMLTI YQLHKICHSRAFQHWELIQEDILDTGDNGNGNGEKEVK IKRIQLYENKPRQYRPKILSYDSY comprising a second amino acid sequence comprising at least a 90% homology to the first Preliminary second amino acid distribution is contiguous, and in sequential order, the isolated chimeric polypeptide coding D56406_PEA_1_P5.

  2. Length “n” (wherein n is at least about 10 amino acids long, optionally at least about 20 amino acids long, preferably at least about 30 amino acids long, more preferably at least about 40 amino acids long, most preferably at least about 50 amino acids in length, at least two amino acids comprising CS, starting from any of the following structures: amino acid numbers 23-x-23, amino acid numbers 24 + ((n-2) -x) (formula D56406_PEA_1_P5 isolated chimeric polypeptide comprising a polypeptide, wherein the polypeptide has a sequence terminating in: x) varying from 0 to n-2).

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein D56406_PEA_1_P5 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column, as shown in Table 179); It indicates whether it is known and the presence of a known SNP in the mutein D56406_PEA_1_P5 sequence supports the deduced sequence of this mutein of the invention).

  The mutein D56406_PEA_1_P5 is encoded by the following transcript: D56406_PEA_1_T6 (sequences shown at the end of the application). The code portion of transcript D56406_PEA_1_T6 is shown in bold, starting at position 106 and ending at position 609. The transcript also has the following SNPs listed in Table 180 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein D56406_PEA_1_P5 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein D56406_PEA_1_P6 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript D56406_PEA_1_T7. An alignment to a known protein (neurotensin / neuromedin N precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of the comparison between D56406_PEA_1_P6 and NEUT_HUMAN 1. The first amino acid sequence corresponding to amino acids 1 to 45 of NEUT_HUMAN, corresponding to amino acids 1 to 45 of D56406_PEA_1_P6, also corresponds to amino acids 121 to 170 of NEUT_HUMAN, amino acids 46 to 95 of D56406_PEA_1_P6, corresponding to amino acids 121 to 170 of NEUT_HUMAN An isolated chimeric polypeptide encoding D56406_PEA_1_P6, comprising a second amino acid sequence which is at least 90% homologous to LIQEDILDTGND KNGKEEVIKRKIPYILKRQLYENKPRRPYILKRDSYYY, which also corresponds to SEQ ID NO: 1, the first and second amino acid sequences being adjacent and in a consecutive order .

  2. Length “n” (wherein n is at least about 10 amino acids long, optionally at least about 20 amino acids long, preferably at least about 30 amino acids long, more preferably at least about 40 amino acids long, most preferably at least about 50 amino acids long, at least two amino acids comprising KL, starting from any of the following structures: amino acids 45-x-45, amino acids 46 + ((n-2) -x) (formula A D56406_PEA_1_P6 isolated chimeric polypeptide comprising a polypeptide, wherein the polypeptide has a sequence terminating in: x) varying from 0 to n-2).

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein D56406_PEA_1_P6 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing the other amino acids, and listing the other amino acids, as shown in Table 181), and the last column contains SNPs It is shown whether it is known and the presence of a known SNP in the mutein D56406_PEA_1_P6 sequence supports the putative sequence of this mutein of the invention).

  The mutein D56406_PEA_1_P6 is encoded by the following transcript: D56406_PEA_1_T7 (sequences shown at the end of the application). The code portion of transcript D56406_PEA_1_T7 is shown in bold and begins at position 106 and ends at position 390. The transcript also has the following SNPs listed in Table 182 (indicating its position on the nucleotide sequence and listing another nucleic acid, the last column indicating whether the SNP is known, mutein D56406_PEA_1_P6 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  As mentioned above, cluster D56406 is characterized by the ten segments listed in Table 2 above, the sequence of which is shown at the end of the application. These segments are part of the nucleic acid sequence, which are of particular interest and are individually described herein. A description of each segment of the invention is provided herein.

  The segment cluster D56406_PEA_1_node_0 of the present invention is supported by 48 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: D56406_PEA_1_T3, D56406_PEA_1_T6, and D56406_PEA_1_T7. Table 183 below describes the start and end positions of this segment on each transcript.

  Microarray (chip) data for this segment is also available, as follows. As described above, with respect to the clusters themselves, different oligonucleotides were tested for differential expression in different disease states, in particular cancer. The following oligonucleotides were found to reach this segment (for lung cancer) (shown in Table 184).

  The segment cluster D56406_PEA_1_node_13 of the present invention is supported by 43 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: D56406_PEA_1_T3, D56406_PEA_1_T6, and D56406_PEA_1_T7. Table 185 below describes the start and end positions of this segment on each transcript.

  According to an optional embodiment of the present invention, there is also provided a short segment associated with the above cluster. These segments are up to about 120 bp in length and are therefore included in the individual descriptions.

  The segment cluster D56406_PEA_1_node_11 of the present invention is supported by one library. The number of libraries was determined as described above. This segment can be found in the following transcript: D56406_PEA_1_T3. Table 186 below describes the start and end positions of this segment on each transcript.

  The segment cluster D56406_PEA_1_node_2 of the invention can be found in the following transcript: D56406_PEA_1_T3 and D56406_PEA_1_T7. Table 187 below describes the start and end positions of this segment on each transcript.

  The segment cluster D56406_PEA_1_node_3 of the present invention is supported by 46 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: D56406_PEA_1_T3, D56406_PEA_1_T6, and D56406_PEA_1_T7. Table 188 below describes the start and end positions of this segment on each transcript.

  The segment cluster D56406_PEA_1_node_5 of the present invention is supported by 48 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: D56406_PEA_1_T3 and D56406_PEA_1_T6. Table 189 below describes the start and end positions of this segment on each transcript.

  The segment cluster D56406_PEA_1_node_6 of the present invention is supported by 34 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: D56406_PEA_1_T3 and D56406_PEA_1_T6. Table 190 below describes the start and end positions of this segment on each transcript.

  The segment cluster D56406_PEA_1_node_7 of the present invention is supported by 32 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: D56406_PEA_1_T3 and D56406_PEA_1_T6. Table 191 below describes the start and end positions of this segment on each transcript.

  The segment cluster D56406_PEA_1_node_8 according to the invention can be found in the following transcript: D56406_PEA_1_T3 and D56406_PEA_1_T6. Table 192 below describes the beginning and ending positions of this segment on each transcript.

  The segment cluster D56406_PEA_1_node_9 of the present invention is supported by 31 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: D56406_PEA_1_T3 and D56406_PEA_1_T6. Table 193 below describes the start and end positions of this segment on each transcript.

Mutated protein alignment against previously known proteins:
Sequence name: / tmp / jU49325aMA / 8F0XuN7La5: NEUT_HUMAN

Sequence documentation:

Alignment of: D56406_PEA_1_P2 x NEUT_HUMAN ..

Alignment segment 1/1:

Quality: 1591.00 Escore: 0
Matching length: 170 Total length: 201
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 84.58 Total Percent Identity: 84.58
Gaps: 1

Alignment:
....
1 MMAGMKIQLVCMLLAFSSWSLCSDSEEEMKALEADFLTNMHTSKISKAH 50
||||||||||||||||||||||||||||||||||||||||
1 MMAGMKIQLVCMLLAFSSWSLCSDSEEEMKALEADFLTNMHTSKISKAH 50
....
51 VPSW KMTLLNVCSL VNNL NSPA EETGEVHEEELVARRKLPTALDGFSLEA 100
||||||||||||||||||||||||||||||||||||||||
51 VPSW KMTLLNVCSL VNNL NSPA EETGEVHEEELVARRKLPTALDGFSLEA 100
....
101 MLTIYQLHKICHSRAFQHEARWLTPIPALWEAETGGSRGQEMETIPAN 150
|||||||||||||||||||
101 MLTIYQLHKICHSRAFQHWE ................................... 120
....
151 TLIQEDILDTGNDKNGKEEVIKRKIPYILKRQLYENKPRRPYILKRDSYY 200
||||||||||||||||||||||||||||||||||||||||
121. LIQEDILDTGNDKNGKEEVIKRKIPYILKRQLYENKPRRPYILKRDSYY 169

201 Y 201
|
170 Y 170






Sequence name: / tmp / wWui8Kd4y9 / zbf3ihRwnR: NEUT_HUMAN

Sequence documentation:

Alignment of: D56406_PEA_1_P5 x NEUT_HUMAN ..

Alignment segment 1/1:

Quality: 1572.00 Escore: 0
Matching length: 168 Total length: 170
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 98.82 Total Percent Identity: 98.82
Gaps: 1

Alignment:
....
1 MMAGMKIQLVCMLLAFSSWSLC..SEEEMKALEADFLTNMHTSKISKAH 48
|||||||||||||||||||||||||||||||||||||||
1 MMAGMKIQLVCMLLAFSSWSLCSDSEEEMKALEADFLTNMHTSKISKAH 50
....
49 VPSWKMTLLNVCSLVNL NNSPA EETGEVHEEEL VARRKLPTALDGFSLEA 98
||||||||||||||||||||||||||||||||||||||||
51 VPSW KMTLLNVCSL VNNL NSPA EETGEVHEEELVARRKLPTALDGFSLEA 100
....
99 MLTIYQLHKICHSRAFQHWELIQEDILDTGDNKNGKEEVIKRKIPYILKR 148
||||||||||||||||||||||||||||||||||||||||
101 MLTIYQLHKICHSRAFQHWELIQEDILDTGDNKNGKEEVIKRKIPYILKR 150
.
149 QLYENKPRRPYILKRDSYYY 168
|||||||||||||||||||
151 QLYENKPRRPYILKRDSYYY 170






Sequence name: / tmp / f5d07fF5D7 / E4N5xjUIAN: NEUT_HUMAN

Sequence documentation:

Alignment of: D56406_PEA_1_P6 x NEUT_HUMAN ..

Alignment segment 1/1:

Quality: 844.00 Escore: 0
Matching length: 95 Total length: 170
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 55.88 Total Percent Identity: 55.88
Gaps: 1

Alignment:
....
1 MMAGMKIQLVCMLLAFSSWSLCSDSEEEMKALEADFLTNHMHTSK ..... 45
|||||||||||||||||||||||||||||||||||||||
1 MMAGMKIQLVCMLLAFSSWSLCSDSEEEMKALEADFLTNMHTSKISKAH 50
....
45 ...................................................... . 45

51 VPSW KMTLLNVCSL VNNL NSPA EETGEVHEEELVARRKLPTALDGFSLEA 100
....
46 ............ LIQEDILDTGNDKNGKEEVIKRKIPYILKR 75
||||||||||||||||||||||||||||
101 MLTIYQLHKICHSRAFQHWELIQEDILDTGDNKNGKEEVIKRKIPYILKR 150
.
76 QLYENKPRRPYILKRDSYYY 95
|||||||||||||||||||
151 QLYENKPRRPYILKRDSYYY 170

Description of Cluster F05068 Cluster F05068 features 3 transcripts of interest and 12 segments, the names of which are shown in Tables 194 and 195, respectively, and the sequences themselves are shown at the end of the application. Selected protein variants are shown in Table 196.

  These sequences are known proteins, previously known herein as ADM precursors (including: adrenomedullin (AM), proadrenomedullin N-20 terminal peptide (ProAM-N20) (ProAMN- A variant of the terminal 20 peptide) (PAMP)) (SwissProt accession identifier ADML_HUMAN) (SEQ ID NO: 1423).

  The protein ADM precursor is known or considered to have the following functions: AM and PAMP are potent antihypertensive and vasodilator. A large number of effects have been reported, with the most mention of the physiological control of fluid and electrolyte homeostasis. In the kidney, AM is a diuretic and natriuretic, and both AM and PAMP inhibit aldosterone secretion by direct adrenal effects. In the pituitary, both peptides inhibit basal ACTH secretion at physiologically relevant doses. Both peptides appear to act to promote a reduction in plasma volume in the brain and in the pituitary body (action to complement its blood pressure lowering action in blood vessels). The sequence of the protein ADM precursor is referred to as "ADM precursor (including: adrenomedullin (AM), pro-adrenomedullin N-20 terminal peptide (ProAM-N20) (ProAMN-terminal 20 peptide) (PAMP)) amino acid sequence" The known polymorphisms of this sequence are shown in Table 197.

  Localization of the protein ADM precursor is considered secretion.

  The following GO annotation applies to previously known proteins. The following annotations were found: annotations related to biological processes: cAMP biosynthesis, progesterone biosynthesis, signal transduction, cell-cell signaling, pregnancy, excretion, circulation, wound response, molecular function Related annotations Ligands, hormones, and stranding spaces that are annotations related to cellular components, soluble fractions.

  GO assignments can be made at one or more http: // www. expasy. SwissProt / TremBl Protein knowledgebase available from ch / sprot / or http: // www. ncbi. nlm. nih. Depends on Locuslink available from gov / projects / LocusLink /.

  Cluster F05068 can be used as a diagnostic marker by overexpression of transcripts of this cluster in cancer. The expression of such transcripts in normal tissues is also shown by the method previously described. The terms "numbers" in the right column of the table and the numbers on the y-axis of FIG. 21 refer to the weighted expression of ESTs in each category as "ppm" (for ESTs of a particular cluster in this category by ppm Ratio of expression to expression of all ESTs).

  In general, as shown for the histograms in FIG. 21 and Table 198, the following results were obtained. This cluster was overexpressed (at least at minimal levels) in the following pathological conditions: uterine malignancy.

  As mentioned above, cluster F05068 is characterized by the three transcripts listed in Table 194 above. These transcripts encode proteins that are variants of ADM precursor. A description of each mutein of the invention is provided herein.

  The mutein F05068_PEA_1_P7 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcripts F05068_PEA_1_T3 and F05068_PEA_1_T6. An alignment to a known protein (ADM precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between F05068_PEA_1_P7 and ADML_HUMAN 1. An isolated chimeric polypeptide encoding F05068_PEA_1_P7, comprising a first amino acid sequence at least 90% homologous to MKLVSVALMYLGSLAFLGADTARLD VASE FRKK corresponding to amino acids 1 to 33 of ADML_HUMAN and also to amino acids 1 to 33 of F05068_PEA_1_P7.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein F05068_PEA_1_P7 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column, as shown in Table 200) It is shown whether it is known and the presence of a known SNP in the mutant protein F05068_PEA_1_P7 sequence supports the predicted sequence of this mutant protein according to the invention).

  The mutein F05068_PEA_1_P7 is encoded by the following transcript: F05068_PEA_1_T3 and F05068_PEA_1_T6 (sequences shown at the end of the application).

  The coding part of the transcript F05068_PEA_1_T3 is shown in bold, starting from position 267 and ending at position 365. The transcript also has the following SNPs listed in Table 201 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein F05068_PEA_1_P7 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The coding part of the transcript F05068_PEA_1_T6 is shown in bold, starting from position 267 and ending at position 365. The transcript also has the following SNPs listed in Table 202 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein F05068_PEA_1_P7 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein F05068_PEA_1_P8 according to the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript F05068_PEA_1_T4. An alignment to a known protein (ADM precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report on comparison between F05068_PEA_1_P8 and ADML_HUMAN 1. MKLVS VALMYLGSL ALFADTALLD VASE corresponding to amino acids 1-82 of FADML_HUMAN and corresponding to amino acids 1-82 of F05068_PEA_1_P8 F05068_PEA_7_P4 and a first amino acid sequence that is at least 90% homologous to at least 90% homologous to Said first and second amino acids comprising a second amino acid sequence which is at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous The distribution is adjacent and in sequential order, F05068_PEA_ Isolated chimeric polypeptide encoding _P8.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein F05068_PEA_1_P8 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows SNPs as shown in Table 203) It is shown whether it is known and the presence of a known SNP in the mutant protein F05068_PEA_1_P8 sequence supports the deduced sequence of this mutant protein according to the invention).

  The mutein F05068_PEA_1_P8 is encoded by the following transcript: F05068_PEA_1_T4 (sequences shown at the end of the application). The code portion of the transcript F05068_PEA_1_T4 is shown in bold, starting from position 267 and ending at position 515. The transcript also has the following SNPs listed in Table 204 (indicating its position on the nucleotide sequence and listing another nucleic acid, the last column indicating whether the SNP is known, mutein F05068_PEA_1_P8 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  As mentioned above, cluster F05068 is characterized by the 12 segments listed in Table 2 above, the sequence of which is shown at the end of the application. These segments are part of the nucleic acid sequence, which are of particular interest and are individually described herein. A description of each segment of the invention is provided herein.

  The segment cluster F05068_PEA_1_node_0 of the present invention is supported by 143 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: F05068_PEA_1_T3, F05068_PEA_1_T4, and F05068_PEA_1_T6. Table 205 below describes the start and end positions of this segment on each transcript.

  The segment cluster F05068_PEA_1_node_10 of the present invention is supported by 127 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: F05068_PEA_1_T3, F05068_PEA_1_T4, and F05068_PEA_1_T6. Table 206 below lists the start and end positions of this segment on each transcript.

  The segment cluster F05068_PEA_1_node_12 of the present invention is supported by 123 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: F05068_PEA_1_T3, F05068_PEA_1_T4, and F05068_PEA_1_T6. Table 207 below lists the start and end positions of this segment on each transcript.

  The segment cluster F05068_PEA_1_node_13 of the present invention is supported by 181 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: F05068_PEA_1_T3, F05068_PEA_1_T4, and F05068_PEA_1_T6. Table 208 below describes the start and end positions of this segment on each transcript.

  The segment cluster F05068_PEA_1_node_4 of the present invention is supported by 15 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: F05068_PEA_1_T3 and F05068_PEA_1_T6. Table 209 below lists the start and end positions of this segment on each transcript.

  The segment cluster F05068_PEA_1_node_8 of the present invention is supported by 13 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: F05068_PEA_1_T4 and F05068_PEA_1_T6. Table 210 below describes the start and end positions of this segment on each transcript.

  According to an optional embodiment of the present invention, there is also provided a short segment associated with the above cluster. These segments are up to about 120 bp in length and are therefore included in the individual descriptions.

  The segment cluster F05068_PEA_1_node_11 of the present invention is supported by 112 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: F05068_PEA_1_T3, F05068_PEA_1_T4, and F05068_PEA_1_T6. Table 211 below lists the start and end positions of this segment on each transcript.

  The segment cluster F05068_PEA_1_node_3 of the present invention is supported by 145 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: F05068_PEA_1_T3, F05068_PEA_1_T4, and F05068_PEA_1_T6. Table 212 below describes the start and end positions of this segment on each transcript.

  The segment cluster F05068_PEA_1_node_5 of the present invention is supported by 124 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: F05068_PEA_1_T3, F05068_PEA_1_T4, and F05068_PEA_1_T6. Table 213 below describes the start and end positions of this segment on each transcript.

  The segment cluster F05068_PEA_1_node_6 of the present invention is supported by 110 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: F05068_PEA_1_T3, F05068_PEA_1_T4, and F05068_PEA_1_T6. Table 214 below describes the start and end positions of this segment on each transcript.

  The segment cluster F05068_PEA_1_node_7 of the present invention is supported by 109 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: F05068_PEA_1_T3, F05068_PEA_1_T4, and F05068_PEA_1_T6. Table 215 below describes the start and end positions of this segment on each transcript.

  The segment cluster F05068_PEA_1_node_9 of the present invention is supported by 114 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: F05068_PEA_1_T3, F05068_PEA_1_T4, and F05068_PEA_1_T6. Table 216 below lists the start and end positions of this segment on each transcript.

Mutated protein alignment against previously known proteins:
Sequence name: / tmp / kEsi3RWsCN / 1svdhjfiNV: ADML_HUMAN

Sequence documentation:

Alignment of: F05068_PEA_1_P7 x ADML_HUMAN ..

Alignment segment 1/1:

Quality: 304.00 Escore: 0
Matching length: 33 Total length: 33
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MKLVSVALMYLGSLAFLGADTARLDVASEFRKK 33
||||||||||||||||||||||||||||||
1 MKLVSVALMYLGSLAFLGADTARLDVASEFRKK 33






Sequence name: / tmp / tcrlWIx4kg / aghbr8Eh8n: ADML_HUMAN

Sequence documentation:

Alignment of: F05068_PEA_1_P8 x ADML_HUMAN ..

Alignment segment 1/1:

Quality: 791.00 Escore: 0
Matching length: 82 Total length: 82
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MKLVSVALMYLGSLAFLGADTARLDVASEFRKKWNKWALSRGKRELRMSS 50
||||||||||||||||||||||||||||||||||||||||
1 MKLVSVALMYLGSLAFLGADTARLDVASEFRKKWNKWALSRGKRELRMSS 50
....
51 SYPTGLADKKAGAP AQTLIRPQDMKGASRSPED 82
||||||||||||||||||||||||||||||
51 SYPTGLADKKAGAP AQTLIRPQDMKGASRSPED 82

Description of cluster H14624 Cluster H14624 is characterized by one transcript and 15 segments of interest, the names of which are shown in Tables 217 and 218, respectively, and the sequence itself is shown at the end of the application. Selected protein variants are shown in Table 219.

  Cluster H14624 can be used as a diagnostic marker by overexpression of transcripts of this cluster in cancer. The expression of such transcripts in normal tissues is also shown by the method previously described. The terms "numbers" in the right column of the table and the numbers on the y-axis of Fig. 22 refer to the weighted expression of ESTs in each category as "ppm" (the ppm of ESTs of a particular cluster in this category by ppm Ratio of expression to expression of all ESTs).

  In general, as shown for the histograms in FIG. 22 and Table 220, the following results were obtained. This cluster was overexpressed (at least at minimal levels) in the following pathological conditions: colorectal cancer, epithelial malignancies, a mixture of malignancies from different tissues, lung malignant brain tumors, and pancreatic cancer.

  As mentioned above, contig H14624 is characterized by one transcript as listed in Table 217 above. A description of each mutein of the invention is provided herein.

  The mutein H14624_P15 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript H14624_T20. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report on comparison between H14624_P15 and Q9 HAP5 (SEQ ID NO: 1701) This is a GH JFH, and corresponds to a GH JH, and is a GH JH JH. At least 70%, optionally at least 80%, preferably at least 85%, more preferably Is an isolated chimera encoding H14624_P15, comprising a second amino acid sequence which is at least 90%, most preferably at least 95% homologous, said first and second amino acid sequences being adjacent and in sequential order Polypeptide.

  2. H14624_P15 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence GKPSLLLPHSLLG in H14624_P15 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein H14624_P15 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows SNPs as shown in Table 222) It indicates whether it is known and the presence of a known SNP in the mutein H14624_P15 sequence supports the deduced sequence of this mutein of the invention).

  The mutein H14624_P15 is encoded by the following transcript: H14624_T20 (sequences shown at the end of the application). The coding portion of transcript H14624_T20 is shown in bold and this coding portion starts at position 857 and ends at position 1396. The transcript also has the following SNPs listed in Table 223 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein H14624_P15 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  As mentioned above, cluster H14624 is characterized by the 15 segments listed in Table 2 above, the sequence of which is shown at the end of the application. These segments are part of the nucleic acid sequence, which are of particular interest and are individually described herein. A description of each segment of the invention is provided herein.

  The segment cluster H14624_node_0 of the present invention is supported by three libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: H14624_T20. Table 224 below describes the start and end positions of this segment on each transcript.

  The segment cluster H14624_node_16 of the present invention is supported by three libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: H14624_T20. Table 225 below describes the start and end positions of this segment on each transcript.

  The segment cluster H14624_node_3 of the present invention is supported by 67 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: H14624_T20. Table 226 below describes the start and end positions of this segment on each transcript.

  According to an optional embodiment of the present invention, there is also provided a short segment associated with the above cluster. These segments are up to about 120 bp in length and are therefore included in the individual descriptions.

  The segment cluster H14624_node_10 according to the invention can be found in the following transcript: H14624_T20. Table 227 below describes the start and end positions of this segment on each transcript.

  The segment cluster H14624_node_11 of the present invention is supported by 99 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: H14624_T20. Table 228 below lists the start and end positions of this segment on each transcript.

  The segment cluster H14624_node_12 according to the invention can be found in the following transcript: H14624_T20. Table 229 below describes the start and end positions of this segment on each transcript.

  The segment cluster H14624_node_13 of the present invention is supported by 124 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: H14624_T20. Table 230 below describes the start and end positions of this segment on each transcript.

  The segment cluster H14624_node_14 of the present invention is supported by 114 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: H14624_T20. Table 231 below lists the start and end positions of this segment on each transcript.

  The segment cluster H14624_node_15 of the present invention is supported by 124 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: H14624_T20. Table 232 below describes the start and end positions of this segment on each transcript.

  The segment cluster H14624_node_4 of the present invention is supported by 65 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: H14624_T20. Table 233 below describes the start and end positions of this segment on each transcript.

  The segment cluster H14624_node_5 according to the invention can be found in the following transcript: H14624_T20. Table 234 below describes the start and end positions of this segment on each transcript.

  The segment cluster H14624_node_6 according to the invention can be found in the following transcript: H14624_T20. Table 235 below describes the start and end positions of this segment on each transcript.

  The segment cluster H14624_node_7 according to the invention can be found in the following transcript: H14624_T20. Table 236 below describes the start and end positions of this segment on each transcript.

  The segment cluster H14624_node_8 of the present invention is supported by 85 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: H14624_T20. Table 237 below describes the start and end positions of this segment on each transcript.

  The segment cluster H14624_node_9 of the present invention is supported by 87 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: H14624_T20. Table 238 below describes the beginning and ending positions of this segment on each transcript.

Mutated protein alignment against previously known proteins:
Sequence name: / tmp / Upb1SbFkrj / N4PrGQAB2V: Q9HAP5

Sequence documentation:

Alignment of: H14624_P15 x Q9HAP5 ..

Alignment segment 1/1:

Quality: 1702.00 Escore: 0
Matching length: 167 Total length: 167
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MLQGPGSLLLLFLASHCCLGSARGLFLFGQPDFSYKRSNCKPIPANLQLC 50
||||||||||||||||||||||||||||||||||||||||
1 MLQGPGSLLLLFLASHCCLGSARGLFLFGQPDFSYKRSNCKPIPANLQLC 50
....
51 HGIEYQNMRLPNLLGHETM KEVLEQAGAWIPLVMKQCHPDTKKFLCSLFA 100
||||||||||||||||||||||||||||||||||||||||
51 HGIEYQNMRLPNLLGHETM KEVLEQAGAWIPLVMKQCHPDTKKFLCSLFA 100
....
101 PVCLDDLDETIQPCHSLCVQVKDRCAPVMSAFGFPWPDMECDRFPQDND 150
||||||||||||||||||||||||||||||||||||||||
101 PVCLDDLDETIQPCHSLCVQVKDRCAPVMSAFGFPWPDMECDRFPQDND 150
.
151 LCIPLASSDHLLPATEE 167
||||||||||||||||
151 LCIPLASSDHLLPATEE 167

Cluster H 38804 Description Cluster H 38804 is characterized by two transcripts of interest and 20 segments, the names of which are shown in Tables 239 and 240, respectively, and the sequence itself is shown at the end of the application. Selected protein variants are shown in Table 241.

  These sequences are variants of the mitotic checkpoint protein BUB3 (SwissProt accession identifier BUB3_HUMAN) (SEQ ID NO: 1424), which is a known protein, referred to herein as a previously known protein.

  The protein mitotic checkpoint protein BUB3 is known or considered to have the following functions: It is required for the centromeric localization of BUB1. The sequence of the protein mitotic checkpoint protein BUB3 is shown at the end of the application as "mitotic checkpoint protein BUB3 amino acid sequence". Known polymorphisms of this sequence are shown in Table 242.

  The localization of the protein mitotic checkpoint protein BUB3 is considered to be the nucleus.

  The following GO annotation applies to previously known proteins. The following annotations were found: annotations related to biological processes: mitosis, mitotic checkpoint, mitotic spindle checkpoint, cell proliferation, and annotated related to cellular components Is the nucleus.

  GO assignments can be made at one or more http: // www. expasy. SwissProt / TremBl Protein knowledgebase available from ch / sprot / or http: // www. ncbi. nlm. nih. Depends on Locuslink available from gov / projects / LocusLink /.

  Cluster H38804 can be used as a diagnostic marker by overexpression of transcripts of this cluster in cancer. The expression of such transcripts in normal tissues is also shown by the method previously described. The terms "numbers" in the right column of the table and the numbers on the y-axis of FIG. 23 refer to the weighted expression of ESTs in each category as "ppm" (for ESTs of a particular cluster in this category by ppm Ratio of expression to expression of all ESTs).

  In general, as shown for the histograms in FIG. 23 and Table 243, the following results were obtained. This cluster was overexpressed (at least at minimal levels) in the following pathological conditions: transitional cell carcinoma, brain malignancy, a mixture of malignancies from different tissues, and gastric cancer.

  As mentioned above, cluster H38804 is characterized by the two transcripts listed in Table 239 above. These transcripts encode a protein that is a mutated form of the protein mitotic checkpoint protein BUB3. A description of each mutein of the invention is provided herein.

  The mutein H38804_PEA_1_P5 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript H38804_PEA_1_T8. An alignment to a known protein (mitotic checkpoint protein BUB3) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between H38804_PEA_1_P5 and BUB3_HUMAN 1. H38804_PEA_1_P5 at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous with the polypeptide having the sequence MGRVRTLAGECSAAQAQSLAVLSAPPS SGGTPSALDPRSGLWAPVLQ corresponding to amino acids 1-57 of H38804 1 amino acid sequence corresponding to amino acids 1-324 of BUB3_HUMAN and corresponding to amino acids 58-381 of H38804_PEA_1_P5, MTGSNEFKLNQPPEDGISSVKFSPNTSQFLLVSSWSLYLYDPASNSMRLKYQHTGAVLDCAFYDPTHAWSGGLDHQLDMGDNTLVEN DAPIRCVEYCPEVNVMVTGSWDQTVKLWDPRTPCNAGTFSQPEKVYTLSVSGDRLIVGTAGRRVLVWDLRNMGYVQQRRESSLKYQTRCIRAFPNKQGYVLSSIEGRVAVEYLDPSPEVQKKKYAFKCHRLKENNIEQIYPVNAISFHNIHNTFATGGSDGFVNIWDPFNKKRLCQFHRYPTSIASLAFSNDGTTLAIASSYMYEMDDTEHPEDGIFIRQVTDAETKPK and and at least 90% homologous to a second amino acid sequence, wherein the first and second amino acid distribution is contiguous, and in sequential order, the isolated chimeric polypeptide coding H38804_PEA_1_P5.

  2. The tip of H38804_PEA_1_P5 comprising the polypeptide of at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence MGRVRTLAGECSAAQAQLASL VSL An isolated polypeptide encoding

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is considered to be secreted as it is presumed that this protein has a signal peptide by one of two signal peptide estimation programs (HMM: Signal peptide, NN: NO).

  The mutein H38804_PEA_1_P5 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column, as shown in Table 245) It indicates whether it is known and the presence of a known SNP in the mutant protein H38804_PEA_1_P5 sequence supports the deduced sequence of this mutant protein according to the invention).

  The mutein H38804_PEA_1_P5 is encoded by the following transcript: H38804_PEA_1_T8 (sequences shown at the end of the application). The coding portion of the transcript H38804_PEA_1_T8 is shown in bold, starting from position 475 and ending at position 1617. The transcript also has the following SNPs listed in Table 246 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein H38804_PEA_1_P5 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein H38804_PEA_1_P17 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript H38804_PEA_1_T24. An alignment to a known protein (mitotic checkpoint protein BUB3) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between H38804_PEA_1_P17 and BUB3_HUMAN 1. H38804_PEA_1_P17 at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous to the polypeptide having the sequence MGRVRTLAGECSAAQAQLASLVSLSPGSPGPLDLSGLWAPAVQ corresponding to amino acids 1 to 57 of H38804 1 amino acid sequence corresponding to amino acids 1 to 328 of BUB3_HUMAN, and corresponding to amino acids 58 to 385 of H38804_PEA_1_P17, MTGSNEFKLNQPPEDGISSVKFSPNTSQFLLVSSWSLYLYDPASNSMRLKYQHTGAVLDCAFYDPTHAWSGGLDHQLDMGDQENLV THDAPIRCVEYCPEVNVMVTGSWDQTVKLWDPRTPCNAGTFSQPEKVYTLSVSGDRLIVGTAGRRVLVWDLRNMGYVQQRRESSLKYQTRCIRAFPNKQGYVLSSIEGRVAVEYLDPSPEVQKKKYAFKCHRLKENNIEQIYPVNAISFHNIHNTFATGGSDGFVNIWDPFNKKRLCQFHRYPTSIASLAFSNDGTTLAIASSYMYEMDDTEHPEDGIFIRQVTDAETKPKSPCT and and at least 90% homologous to a second amino acid sequence, wherein the first and second amino acid distribution is contiguous, and in sequential order, the isolated chimeric polypeptide coding H38804_PEA_1_P17.

  2. H38804_PEA_1_P17 the tip of H38804_PEA_1_P17 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence MGRVRTLAGECSAAQAQLASLV An isolated polypeptide encoding

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is considered to be secreted as it is presumed that this protein has a signal peptide by one of two signal peptide estimation programs (HMM: Signal peptide, NN: NO).

  The mutein H38804_PEA_1_P17 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing the other amino acids, and listing the other amino acids, as shown in Table 247; It is shown whether it is known and the presence of a known SNP in the mutant protein H38804_PEA_1_P17 sequence supports the deduced sequence of this mutant protein of the invention).

  The mutein H38804_PEA_1_P17 is encoded by the following transcript: H38804_PEA_1_T24 (sequences shown at the end of the application). The coding portion of the transcript H38804_PEA_1_T24 is shown in bold, starting from position 475 and ending at position 1629. The transcript also has the following SNPs listed in Table 248 (showing its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein H38804_PEA_1_P17 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  As mentioned above, cluster H38804 is characterized by the 20 segments listed in Table 2 above, the sequence of which is shown at the end of the application. These segments are part of the nucleic acid sequence, which are of particular interest and are individually described herein. A description of each segment of the invention is provided herein.

  The segment cluster H38804_PEA_1_node_0 of the present invention is supported by 125 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: H38804_PEA_1_T24 and H38804_PEA_1_T8. Table 249 below describes the start and end positions of this segment on each transcript.

  The segment cluster H38804_PEA_1_node_1 of the present invention is supported by nine libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: H38804_PEA_1_T24 and H38804_PEA_1_T8. Table 250 below describes the start and end positions of this segment on each transcript.

  The segment cluster H38804_PEA_1_node_16 of the present invention is supported by 214 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: H38804_PEA_1_T24 and H38804_PEA_1_T8. Table 251 below describes the start and end positions of this segment on each transcript.

  The segment cluster H38804_PEA_1_node_19 of the present invention is supported by 198 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: H38804_PEA_1_T24 and H38804_PEA_1_T8. Table 252 below describes the start and end positions of this segment on each transcript.

  The segment cluster H38804_PEA_1_node_24 of the present invention is supported by 180 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: H38804_PEA_1_T24 and H38804_PEA_1_T8. Table 253 below describes the start and end positions of this segment on each transcript.

  The segment cluster H38804_PEA_1_node_25 of the present invention is supported by 28 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: H38804_PEA_1_T8. Table 254 below describes the start and end positions of this segment on each transcript.

  The segment cluster H38804_PEA_1_node_28 of the present invention is supported by 38 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: H38804_PEA_1_T8. Table 255 below describes the start and end positions of this segment on each transcript.

  The segment cluster H38804_PEA_1_node_29 of the present invention is supported by 259 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: H38804_PEA_1_T24 and H38804_PEA_1_T8. Table 256 below describes the start and end positions of this segment on each transcript.

  The segment cluster H38804_PEA_1_node_30 of the present invention is supported by 169 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: H38804_PEA_1_T24 and H38804_PEA_1_T8. Table 257 below describes the start and end positions of this segment on each transcript.

  According to an optional embodiment of the present invention, there is also provided a short segment associated with the above cluster. These segments are up to about 120 bp in length and are therefore included in the individual descriptions.

  The segment cluster H38804_PEA_1_node_10 of the present invention is supported by 179 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: H38804_PEA_1_T24 and H38804_PEA_1_T8. Table 258 below describes the start and end positions of this segment on each transcript.

  The segment cluster H38804_PEA_1_node_12 of the present invention is supported by 181 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: H38804_PEA_1_T24 and H38804_PEA_1_T8. Table 259 below describes the start and end positions of this segment on each transcript.

  The segment cluster H38804_PEA_1_node_13 of the present invention is supported by 187 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: H38804_PEA_1_T24 and H38804_PEA_1_T8. Table 260 below describes the start and end positions of this segment on each transcript.

  The segment cluster H38804_PEA_1_node_14 of the present invention is supported by 179 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: H38804_PEA_1_T24 and H38804_PEA_1_T8. Table 261 below describes the start and end positions of this segment on each transcript.

  The segment cluster H38804_PEA_1_node_2 of the present invention is supported by 156 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: H38804_PEA_1_T24 and H38804_PEA_1_T8. Table 262 below describes the start and end positions of this segment on each transcript.

  The segment cluster H38804_PEA_1_node_20 of the present invention is supported by 162 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: H38804_PEA_1_T24 and H38804_PEA_1_T8. Table 263 below describes the start and end positions of this segment on each transcript.

  The segment cluster H38804_PEA_1_node_23 according to the invention can be found in the following transcript: H38804_PEA_1_T24 and H38804_PEA_1_T8. Table 264 below describes the start and end positions of this segment on each transcript.

  The segment cluster H38804_PEA_1_node_26 of the present invention is supported by 21 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: H38804_PEA_1_T8. Table 265 below describes the beginning and ending positions of this segment on each transcript.

  The segment cluster H38804_PEA_1_node_3 of the present invention is supported by 162 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: H38804_PEA_1_T24 and H38804_PEA_1_T8. Table 266 below describes the start and end positions of this segment on each transcript.

  The segment cluster H38804_PEA_1_node_4 of the present invention is supported by 172 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: H38804_PEA_1_T24 and H38804_PEA_1_T8. Table 267 below describes the start and end positions of this segment on each transcript.

  The segment cluster H38804_PEA_1_node_5 according to the invention can be found in the following transcript: H38804_PEA_1_T24 and H38804_PEA_1_T8. Table 268 below describes the start and end positions of this segment on each transcript.

Mutated protein alignment against previously known proteins:
Sequence name: / tmp / RR4oV8zYLg / QlORqeqpIp: BUB3_HUMAN

Sequence documentation:

Alignment of: H38804_PEA_1_P5 x BUB3_HUMAN ..

Alignment segment 1/1:

Quality: 3244.00 Escore: 0
Matching length: 324 Total length: 324
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
58 MTGSNEFKLNQPPEDGIS SVKF SPNT SQFLLVSS WDTSVRLYDVPANSMR 107
||||||||||||||||||||||||||||||||||||||||
1 MTGSNEFKLNQPPEDGISSVKFSPNTSQFLLVSSWDTSVRLYDVPANSMR 50
....
108 LKYQHTGAVLDCAFYDPTHAWSGGLDHQLKMDLNTDQENLVGTHDAPIR 157
||||||||||||||||||||||||||||||||||||||||
51 LKYQHTGAVLDCAFYDPTHAWSGGLDHQLKMDLNTDQENLVGTHDAPIR 100
....
158 CVEYCPEVNMVMTGSWDQTVKLWDPRTPCNAGTFSQPEKVYTLSVSGDRL 207
||||||||||||||||||||||||||||||||||||||||
101 CVEYCPEVNMVMTGSWDQTVKLWDPRTPCNAGTFSQPEKVYTLSVSGDRL 150
....
208 IGGTAGRRVLVWDLRNMGYVQQRRESSLKYQTRCIRAFPNKQGYVLSSIE 257
||||||||||||||||||||||||||||||||||||||||
151 IVGTAGRRVLVWDLRNMGYVQQRRESSLKYQTRCIRAFPNKQGYVLSSIE 200
....
258 GRVAVEYLDPSPEVQKKKYAFKCHRLKENNIEQ IYPVNAISFHNIHTFA 307
||||||||||||||||||||||||||||||||||||||||
201 GRVAVEYLDPSPEVQKKKYAFKCHRLKENNIEQ IYPVNAISFHNIHNTFA 250
....
308 TGGSDGFVNIWDPFNKKRLCQFHRYPTSIASLAFSNDGTTLAIASSYMYE 357
||||||||||||||||||||||||||||||||||||||||
251 TGGSDGFVNIWDPFNKKRLCQFHRYPTSIASLAFSNDGTTLAIASSYMYE 300
.
358 MDDTEHPEDGIFIRQVTDAETKP 381
|||||||||||||||||||||||
301 MDDTEHPEDGIFIRQVTDAETKPK 324




Sequence name: / tmp / Db0dQEpSuo / Lr8HPXaeBg: BUB3_HUMAN

Sequence documentation:

Alignment of: H38804_PEA_1_P17 x BUB3_HUMAN ..

Alignment segment 1/1:

Quality: 3288.00 Escore: 0
Matching length: 328 Total length: 328
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
58 MTGSNEFKLNQPPEDGIS SVKF SPNT SQFLLVSS WDTSVRLYDVPANSMR 107
||||||||||||||||||||||||||||||||||||||||
1 MTGSNEFKLNQPPEDGISSVKFSPNTSQFLLVSSWDTSVRLYDVPANSMR 50
....
108 LKYQHTGAVLDCAFYDPTHAWSGGLDHQLKMDLNTDQENLVGTHDAPIR 157
||||||||||||||||||||||||||||||||||||||||
51 LKYQHTGAVLDCAFYDPTHAWSGGLDHQLKMDLNTDQENLVGTHDAPIR 100
....
158 CVEYCPEVNMVMTGSWDQTVKLWDPRTPCNAGTFSQPEKVYTLSVSGDRL 207
||||||||||||||||||||||||||||||||||||||||
101 CVEYCPEVNMVMTGSWDQTVKLWDPRTPCNAGTFSQPEKVYTLSVSGDRL 150
....
208 IGGTAGRRVLVWDLRNMGYVQQRRESSLKYQTRCIRAFPNKQGYVLSSIE 257
||||||||||||||||||||||||||||||||||||||||
151 IVGTAGRRVLVWDLRNMGYVQQRRESSLKYQTRCIRAFPNKQGYVLSSIE 200
....
258 GRVAVEYLDPSPEVQKKKYAFKCHRLKENNIEQ IYPVNAISFHNIHTFA 307
||||||||||||||||||||||||||||||||||||||||
201 GRVAVEYLDPSPEVQKKKYAFKCHRLKENNIEQ IYPVNAISFHNIHNTFA 250
....
308 TGGSDGFVNIWDPFNKKRLCQFHRYPTSIASLAFSNDGTTLAIASSYMYE 357
||||||||||||||||||||||||||||||||||||||||
251 TGGSDGFVNIWDPFNKKRLCQFHRYPTSIASLAFSNDGTTLAIASSYMYE 300
.
358 MDDTEHPEDGIFIRQVTDAETKPKSPCT 385
||||||||||||||||||||||||||
301 MDDTE HPED GIFIRQVTDAETKP KSPCT 328

Description of cluster HSENA 78 The cluster HSENA 78 features one transcript and 7 segments of interest, the names of which are shown in Tables 269 and 270, respectively, and the sequence itself is shown at the end of the application. Selected protein variants are shown in Table 271.

  These sequences are Small Inducible Cytokine B5 Precursor (SwissProt Accession Identifier SZ05_HUMAN, synonym CXCL5, synonym for CXCL5, an epithelial derived neutrophil), which is a known protein, previously known herein as a protein. Activation protein 78, a variant of (also known as neutrophil activation peptide ENA-78) (SEQ ID NO: 1425).

  The small protein inducible cytokine B5 precursor is known or is considered to have the following function: involved in neutrophil activation. The sequence of the small protein inducible cytokine B5 precursor is shown at the end of the application as "small inducible cytokine B5 precursor amino acid sequence". Localization of the small protein inducible cytokine B5 precursor is considered secretion.

  The following GO annotation applies to previously known proteins. The following annotations were found: annotation related to biological processes: chemotaxis, signal transduction, cell-cell signaling, positive control of cell proliferation, chemokines related to molecular function .

  GO assignments can be made at one or more http: // www. expasy. SwissProt / TremBl Protein knowledgebase available from ch / sprot / or http: // www. ncbi. nlm. nih. Depends on Locuslink available from gov / projects / LocusLink /.

  Cluster HSENA 78 can be used as a diagnostic marker by overexpression of transcripts of this cluster in cancer. The expression of such transcripts in normal tissues is also shown by the method previously described. The terms "numbers" in the right column of the table and the numbers on the y-axis of FIG. 24 refer to the weighted expression of ESTs in each category as "ppm" (the ppm of ESTs of a particular cluster in this category by ppm) Ratio of expression to expression of all ESTs).

  As shown generally for the histograms in FIG. 24 and Table 272, the following results were obtained. This cluster was overexpressed (at least at minimal levels) in the following pathological conditions: epithelial malignancy and lung malignancy.

  As mentioned above, cluster HSENA 78 is characterized by one transcript as listed in Table 269 above. These transcripts encode proteins which are variants of the small protein inducible cytokine B5 precursor. A description of each mutein of the invention is provided herein.

  The mutein HSENA 78_P2 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript HSENA 78_T5. An alignment to a known protein (small inducible cytokine B5 precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of the comparison between HSENA 78_P2 and SZ05_HUMAN 1. MSLLSSRAARVPPSSSLCALL VLLLLLT GPGPIASAGPAAVLRELRCV CLQTT QGVHPK MISNLQ VFAIGPQCSKVEVV corresponding to amino acids 1-81 of SZ05_HUMAN and corresponding to amino acids 1-81 of HSENA 78_P2 An isolated chimeric polypeptide comprising HSENA 78_P2 comprising a first amino acid sequence at least 90% homologous to VIVAIGPQCSKVEVV.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein HSENA 78_P2 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows SNPs as shown in Table 274) It is indicated whether it is known and the presence of a known SNP in the mutant protein HSENA 78_P2 sequence supports the deduced sequence of this mutant protein according to the invention).

  The mutein HSENA 78_P2 is encoded by the following transcript: HSENA 78_T5 (sequences shown at the end of the application). The coding portion of the transcript HSENA 78_T5 is shown in bold, starting from position 149 and ending at position 391. The transcript also has the following SNPs listed in Table 275 (showing its position on the nucleotide sequence, listing another nucleic acid, the last column indicating if the SNP is known, mutein HSENA 78_P2 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  As noted above, cluster HSENA 78 features the seven segments listed in Table 270 above, the sequences of which are shown at the end of the application. These segments are part of the nucleic acid sequence, which are of particular interest and are individually described herein. A description of each segment of the invention is provided herein.

  The segment cluster HSENA 78_node_0 of the present invention is supported by 24 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HSENA 78_T5. Table 276 below describes the start and end positions of this segment on each transcript.

  The segment cluster HSENA 78_node_2 of the present invention is supported by 22 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HSENA 78_T5. Table 277 below describes the start and end positions of this segment on each transcript.

  The segment cluster HSENA 78_node 6 of the present invention is supported by 68 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HSENA 78_T5. Table 278 below describes the start and end positions of this segment on each transcript.

  The segment cluster HSENA 78_node_9 of the present invention is supported by 28 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HSENA 78_T5. Table 279 below describes the start and end positions of this segment on each transcript.

  According to an optional embodiment of the present invention, there is also provided a short segment associated with the above cluster. These segments are up to about 120 bp in length and are therefore included in the individual descriptions.

  The segment cluster HSENA 78_node_3 of the present invention is supported by one library. The number of libraries was determined as described above. This segment can be found in the following transcript: HSENA 78_T5. Table 280 below describes the start and end positions of this segment on each transcript.

  The segment cluster HSENA 78_node_4 of the present invention is supported by 17 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HSENA 78_T5. Table 281 below describes the start and end positions of this segment on each transcript.

  The segment cluster HSENA 78_node_8 according to the invention can be found in the following transcript: HSENA 78_T5. Table 282 below describes the start and end positions of this segment on each transcript.

Mutated protein alignment against previously known proteins:
Sequence name: / tmp / 5kiQY6MxWx / pLnTrxsCqk: SZ05_HUMAN

Sequence documentation:

Alignment of: HSENA 78_P2 x SZ05_HUMAN ..

Alignment segment 1/1:

Quality: 767.00 Escore: 0
Matching length: 81 Total length: 81
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MSLLSSRAARVPPSSSLCALLLLLLLTQPGPIASGPAAVLRELRCV 50
||||||||||||||||||||||||||||||||||||||||
1 MSLLSSRAARVPPSSSLCALLLLLLLTQPGPIASGPAAVLRELRCV 50
....
51 CLQTTQGVHPKMISNLQVFAIGPQCSKVEVV 81
|||||||||||||||||||||||||||||
51 CLQTTQGVHPKMISNLQVFAIGPQCSKVEVV 81

Description of cluster HUMODCA The cluster HUMODCA is characterized by one transcript and 17 segments of interest, the names of which are given in Tables 283 and 284, respectively, and the sequence itself is given at the end of the application. Selected protein variants are shown in Table 285.

  These sequences are the known proteins ornithine decarboxylase (SwissProt accession identifier DCOR_HUMAN, synonym EC4.1.1.17, also known as ODC), which is a known protein, previously known herein as a protein. (SEQ ID NO: 1426) is a mutated form.

  The protein ornithine decarboxylase is known or is considered to have the following function: polyamine biosynthesis, first (rate-limiting) step. The sequence of the protein ornithine decarboxylase is shown at the end of the application as "ornithine decarboxylase amino acid sequence". Known polymorphisms of this sequence are shown in Table 286.

  The following GO annotation applies to previously known proteins. The following annotations were found: ornithine decarboxylase, a lyase, which is an annotation related to polyamine biosynthesis and molecular function which is an annotation related to biological processes.

  GO assignments can be made at one or more http: // www. expasy. SwissProt / TremBl Protein knowledgebase available from ch / sprot / or http: // www. ncbi. nlm. nih. Depends on Locuslink available from gov / projects / LocusLink /.

  The cluster HUMODCA can be used as a diagnostic marker by overexpression of transcripts of this cluster in cancer. The expression of such transcripts in normal tissues is also shown by the method previously described. The terms "numbers" in the right column of the table and the numbers on the y-axis of FIG. 25 refer to the weighted expression of ESTs in each category as "ppm" (for ESTs of a particular cluster in this category by ppm Ratio of expression to expression of all ESTs).

  In general, as shown for the histograms in FIG. 25 and Table 287, the following results were obtained. This cluster was overexpressed (at least at minimal levels) in the following pathological conditions: brain malignancy, colorectal cancer, epithelial malignancy, and a mixture of malignancies from different tissues.

  As mentioned above, cluster HUMODCA is characterized by one transcript as listed in Table 283 above. These transcripts encode proteins which are variants of the protein ornithine decarboxylase. A description of each mutein of the invention is provided herein.

  The mutein HUMODCA_P9 according to the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript HUMODCA_T17. An alignment to a known protein (ornithine decarboxylase) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report on comparison between HUMODCA_P9 and DCOR_HUMAN 1. At least 70%, optionally at least 80%, preferably at least 85%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous to a polypeptide having the sequence MKSLTATSSMKVLLPRTFTRKLMKFLLL corresponding to amino acids 1-29 of HUMODCA_P9 1 and an amino acid sequence of DCOR_HUMAN corresponding to amino acids 151 to 461, and corresponding to amino acids 30 to 340 of HUMODCA_P9 LVLRIA TDD SKAVCRL SVKGA GRTLS RLLL EREKALN ID V VG SF HV GS GC TD PET FV AAIS DARC VFD MGF SAFTLAVNIIAKKIVLKEQTGSDDEDESSEQTFMYYVNDGVYGSFNCILYDHAHVKPLLQKRPKPDEKYYSSSIWGPTCDGLDRIVERCDLPEMHVGDWMLFENMGAYTVAAASTFNGFQRPTIYYVMSGPAWQLMQQFQNPDFPPEVEEQDASTLPVSCAWESGMKRHRAACASASINV and and at least 90% homologous to a second amino acid sequence, wherein the first and second amino acid distribution is contiguous, and in sequential order, the isolated chimeric polypeptide coding HUMODCA_P9.

  2. The tip of HUMODCA_P9 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence MKSLTATSSMKVLLPRTFTRKLMKFLLL of HUMODCA_P9 An isolated polypeptide encoding

Report of the comparison between HUMODCA_P9 and AAA59968 (SEQ ID NO: 1702) At least 70%, optionally at least 80%, preferably at least 85%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous to a polypeptide having the sequence MKSLTATSSMKVLLPRTFTRKLMKFLLL corresponding to amino acids 1-29 of HUMODCA_P9 The amino acid sequence of 1 and amino acid 40 to 350 of AAA59968 and corresponding to amino acid 30 to 340 of HUMODCA_P9 LVLRIA TDD SKAVCRL SVKGA TLRTSRLL ERRA EKEL NID VVG SF GS GSD TPET FV TLAVNIIAKKIVLKEQTGSDDEDESSEQTFMYYVNDGVYGSFNCILYDHAHVKPLLQKRPKPDEKYYSSSIWGPTCDGLDRIVERCDLPEMHVGDWMLFENMGAYTVAAASTFNGFQRPTIYYVMSGPAWQLMQQFQNPDFPPEVEEQDASTLPVSCAWESGMKRHRAACASASINV and and at least 90% homologous to a second amino acid sequence, wherein the first and second amino acid distribution is contiguous, and in sequential order, the isolated chimeric polypeptide coding HUMODCA_P9.

  2. The tip of HUMODCA_P9 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence MKSLTATSSMKVLLPRTFTRKLMKFLLL of HUMODCA_P9 An isolated polypeptide encoding

Report of the comparison between HUMODCA_P9 and AAH14562 (SEQ ID NO: 1703) At least 70%, optionally at least 80%, preferably at least 85%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous to a polypeptide having the sequence MKSLTATSSMKVLLPRTFTRKLMKFLLL corresponding to amino acids 1-29 of HUMODCA_P9 1 and the amino acid sequence of AAH14562 corresponding to amino acids 86 to 396 and corresponding to amino acids 30 to 340 of HUMODCA_P9 LVLRIA TDD SKAVCRL SVKGA TLRTSRLL ERRA KELN ID V VG SF HV GS GC TD PET FV TLAVNIIAKKIVLKEQTGSDDEDESSEQTFMYYVNDGVYGSFNCILYDHAHVKPLLQKRPKPDEKYYSSSIWGPTCDGLDRIVERCDLPEMHVGDWMLFENMGAYTVAAASTFNGFQRPTIYYVMSGPAWQLMQQFQNPDFPPEVEEQDASTLPVSCAWESGMKRHRAACASASINV and and at least 90% homologous to a second amino acid sequence, wherein the first and second amino acid distribution is contiguous, and in sequential order, the isolated chimeric polypeptide coding HUMODCA_P9.

  2. The tip of HUMODCA_P9 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence MKSLTATSSMKVLLPRTFTRKLMKFLLL of HUMODCA_P9 An isolated polypeptide encoding

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein HUMODCA_P9 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing the other amino acids, and listing the other amino acids, as shown in Table 289) It is indicated whether it is known and the presence of a known SNP in the mutant protein HUMODCA_P9 sequence supports the deduced sequence of this mutant protein according to the invention).

  The mutein HUMODCA_P9 is encoded by the following transcript: HUMODCA_T17 (sequences shown at the end of the application). The coding part of the transcript HUMODCA_T17 is shown in bold, starting from position 528 and ending at position 1547. The transcript also has the following SNPs listed in Table 290 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, the mutein HUMODCA_P9 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  As noted above, cluster HUMODCA is characterized by the 17 segments listed in Table 284 above, the sequences of which are shown at the end of the application. These segments are part of the nucleic acid sequence, which are of particular interest and are individually described herein. A description of each segment of the invention is provided herein.

  The segment cluster HUMODCA_node_1 of the present invention is supported by 76 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMODCA_T17. Table 291 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMODCA_node_25 of the present invention is supported by 190 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMODCA_T17. Table 292 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMODCA_node_32 of the present invention is supported by 249 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMODCA_T17. Table 293 below describes the start and end positions of this segment on each transcript.

The segment cluster HUMODCA_node_36 of the present invention is 348
Supported by a library. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMODCA_T17. Table 294 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMODCA_node_39 of the present invention is supported by 297 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMODCA_T17. Table 295 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMODCA_node_41 of the present invention is supported by 230 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMODCA_T17. Table 296 below describes the start and end positions of this segment on each transcript.

  According to an optional embodiment of the present invention, there is also provided a short segment associated with the above cluster. These segments are up to about 120 bp in length and are therefore included in the individual descriptions.

  The segment cluster HUMODCA_node_0 of the present invention is supported by nine libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMODCA_T17. Table 297 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMODCA_node_10 of the present invention is supported by 107 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMODCA_T17. Table 298 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMODCA_node_12 of the present invention is supported by 132 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMODCA_T17. Table 299 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMODCA_node_13 of the present invention is supported by 126 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMODCA_T17. Table 300 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMODCA_node_2 of the present invention is supported by 81 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMODCA_T17. Table 301 below lists the start and end positions of this segment on each transcript.

  The segment cluster HUMODCA_node_27 of the present invention is supported by 185 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMODCA_T17. Table 302 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMODCA_node_3 of the present invention is supported by 85 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMODCA_T17. Table 303 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMODCA_node_30 of the present invention is supported by 196 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMODCA_T17. Table 304 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMODCA_node_34 of the present invention is supported by 259 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMODCA_T17. Table 305 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMODCA_node_38 of the present invention is supported by 272 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMODCA_T17. Table 306 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMODCA_node_40 of the present invention is supported by 239 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMODCA_T17. Table 307 below describes the start and end positions of this segment on each transcript.

Mutated protein alignment against previously known proteins:
Sequence name: / tmp / y03EwE6i01 / dRQ5l2K6e2: DCOR_HUMAN

Sequence documentation:

Alignment of: HUMODCA_P9 x DCOR_HUMAN ..

Alignment segment 1/1:

Quality: 3056.00 Escore: 0
Matching length: 311 Total length: 311
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
30 LVLRIA TDD SK AVC RL SV KF GATLRTS RLL LER ER KELN ID V VG V SF HVGS 79
||||||||||||||||||||||||||||||||||||||||
151 LVLRIATDDD SKAVCRL SVKFGATLRTSLLLLERAKELNIDVVG VSFHVGS 200
....
80 GCTDPETFVQAISDARCVFDMGAEVGFSMYLLDIGGGFPGSEDVKLKFEE 129
||||||||||||||||||||||||||||||||||||||||
201 GCTDPETFVQAISDARCLVFDMGAEVGFSMYLLDIGGGFPGSEDVKLKFEE 250
....
130 ITGVINPALDKYFPSDSGVRIIAEGPRYYVASAFTLAVNII AKKIVLKEQ 179
||||||||||||||||||||||||||||||||||||||||
251 ITGVINPALDKYFPSDSDVRIIAEPGRYYVASAFTLAVNII AKKIVLKEQ 300
....
180 TGSDDEDESSEQTF MYYVNDGVYGSFNCILYDHAHVKPLLQKRPKPDEKY 229
||||||||||||||||||||||||||||||||||||||||
301 TGSDDEDESSEQTF MYYVNDGVYGSFNCILYDHAHVKPLLQKRPKPDEKY 350
....
230 YSSSIWGPTCDGLDRIVERCDLPEMVHVGDWMLFENMGAYTVAAASTFNGF 279
||||||||||||||||||||||||||||||||||||||||
351 YSSSIWGPTCDGLDRIVERCDLPEMVHVGDWMLFENMGAYTVAAASTFNGF 400
....
280 QRPTIYYVMSGPAWQLMQQFQNPDFPPEVEEQDASTLPVSAWESGMKRH 329
||||||||||||||||||||||||||||||||||||||||
401 QRPTIYYVMSGPAWQLMQQFQNPDFPPEVEEQDASTLPVSAWESGMKRH 450
.
330 RAACASASINV 340
|||||||||||
451 RAACASASINV 461






Sequence name: / tmp / y03EwE6i01 / dRQ5l2K6e2: AAA59968

Sequence documentation:

Alignment of: HUMODCA_P9 x AAA59968 ..

Alignment segment 1/1:

Quality: 3056.00 Escore: 0
Matching length: 311 Total length: 311
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
30 LVLRIA TDD SK AVC RL SV KF GATLRTS RLL LER ER KELN ID V VG V SF HVGS 79
||||||||||||||||||||||||||||||||||||||||
40 LVLRIA TDD SKAVCRL SVKFGATLRTSLRLLERAKELNIDVVGVSFHVGS 89
....
80 GCTDPETFVQAISDARCVFDMGAEVGFSMYLLDIGGGFPGSEDVKLKFEE 129
||||||||||||||||||||||||||||||||||||||||
90 GCTDPETFVQAISDARCVFDMGAEVGFSMYLLDIGGGFPGSEDVKLKFEE 139
....
130 ITGVINPALDKYFPSDSGVRIIAEGPRYYVASAFTLAVNII AKKIVLKEQ 179
||||||||||||||||||||||||||||||||||||||||
140 ITGVINPALDKYFPSDSGVRIIAEPGRYYVASAFTLAVNII AKKI VLKEQ 189
....
180 TGSDDEDESSEQTF MYYVNDGVYGSFNCILYDHAHVKPLLQKRPKPDEKY 229
||||||||||||||||||||||||||||||||||||||||
190 TGSDDEDESSEQTF MYYVNDGVYGSFNCILYDHAHVKPLLQKRPKPDEKY 239
....
230 YSSSIWGPTCDGLDRIVERCDLPEMVHVGDWMLFENMGAYTVAAASTFNGF 279
||||||||||||||||||||||||||||||||||||||||
240 YSSSIWGPTCDGLDRIVERCDLPEMVHVGDWMLFENMGAYTVAAASTFNGF 289
....
280 QRPTIYYVMSGPAWQLMQQFQNPDFPPEVEEQDASTLPVSAWESGMKRH 329
||||||||||||||||||||||||||||||||||||||||
290 QRPTIYYVMSGPAWQLMQQFQNPDFPPEVEEQDASTLPVISAWESGMKRH 339
.
330 RAACASASINV 340
|||||||||||
340 RAACASASINV 350






Sequence name: / tmp / y03EwE6i01 / dRQ5l2K6e2: AAH14562

Sequence documentation:

Alignment of: HUMODCA_P9 x AAH14562 ..

Alignment segment 1/1:

Quality: 3056.00 Escore: 0
Matching length: 311 Total length: 311
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
30 LVLRIA TDD SK AVC RL SV KF GATLRTS RLL LER ER KELN ID V VG V SF HVGS 79
||||||||||||||||||||||||||||||||||||||||
86 LVLRIATDKSKAVCRLSVKFGATLRTSLRLLERAKELNIDVVGVSFHVGS 135
....
80 GCTDPETFVQAISDARCVFDMGAEVGFSMYLLDIGGGFPGSEDVKLKFEE 129
||||||||||||||||||||||||||||||||||||||||
136 GCTDPETFVQ AISDARCLVFDMGAEVGFSMYLLDIGGGFPGSEDVKLKFEE 185
....
130 ITGVINPALDKYFPSDSGVRIIAEGPRYYVASAFTLAVNII AKKIVLKEQ 179
||||||||||||||||||||||||||||||||||||||||
186 ITGVINPALDKYFPSDSGVRIIAEGPRYYVASAFTLAVNII AKKI VLKEQ 235
....
180 TGSDDEDESSEQTF MYYVNDGVYGSFNCILYDHAHVKPLLQKRPKPDEKY 229
||||||||||||||||||||||||||||||||||||||||
236 TGSDDEDESSEQTF MYYVNDGVYGSFNCILYDHAHVKPLLQKRPKPDEKY 285
....
230 YSSSIWGPTCDGLDRIVERCDLPEMVHVGDWMLFENMGAYTVAAASTFNGF 279
||||||||||||||||||||||||||||||||||||||||
286 YSSSIWGPTCDGLDRIVERCDLPEMVHVGDWMLFENMGAYTVAAASTFNGF 335
....
280 QRPTIYYVMSGPAWQLMQQFQNPDFPPEVEEQDASTLPVSAWESGMKRH 329
||||||||||||||||||||||||||||||||||||||||
336 QRPTIYYVMSGPAWQLMQQFQNPDFPPEVEEQDASTLPVISAWESGMKRH 385
.
330 RAACASASINV 340
|||||||||||
386 RAACASASINV 396

Description of cluster R00299 Cluster R00299 features one transcript and 12 segments of interest, the names of which are shown in Tables 308 and 309, respectively, and the sequence itself is shown at the end of the application. Selected protein variants are shown in Table 310.

  These sequences are variants of the known protein Tescalcin (SwissProt accession identifier TESC_HUMAN, also known as synonym TSC) (SEQ ID NO: 1427), a known protein, previously known herein as a protein. It is.

  The protein tescalcin is known or considered to have the following function: It binds calcium. The sequence of the protein Tescalcin is shown at the end of the application as "Tescalcin amino acid sequence".

  The following GO annotation applies to previously known proteins. The following annotations were found: calcium binding, which is an annotation related to molecular function.

  GO assignments can be made at one or more http: // www. expasy. SwissProt / TremBl Protein knowledgebase available from ch / sprot / or http: // www. ncbi. nlm. nih. Depends on Locuslink available from gov / projects / LocusLink /.

  Cluster R00299 can be used as a diagnostic marker by overexpression of transcripts of this cluster in cancer. The expression of such transcripts in normal tissues is also shown by the method previously described. The terms "numbers" in the right column of the table and the numbers on the y-axis of Fig. 26 refer to the weighted expression of ESTs in each category as "ppm" (for ESTs of a particular cluster in this category by ppm Ratio of expression to expression of all ESTs).

  In general, as shown for the histograms in FIG. 26 and Table 311, the following results were obtained. This cluster was overexpressed (at least at minimal levels) in the following pathological conditions: lung malignancy.

  As mentioned above, cluster R00299 features one transcript as listed in Table 308 above. These transcripts encode a protein which is a mutated form of the protein tescalcin. A description of each mutein of the invention is provided herein.

  The mutein R00299_P3 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript R00299_T2. An alignment to a known protein (Tescalcin) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between R00299_P3 and Q9NWT9 (SEQ ID NO: 1704) At least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous to a polypeptide having the sequence MAEKALLCPSSAGLGTWPWVLNSAWPVLPLAVDQGVDWRPRGPV corresponding to amino acids 1-44 of R00299_P3 1 amino acid sequence corresponding to amino acids 74 to 191 of Q9NWT9 and corresponding to amino acids 45 to 162 of R00299_P3 SSDQIEQLHRRFKQLSGDQPTIRKENFNNVPDELNPIRSK IRNAPRDNASRDRNRNRKGPSGLADEINFEDLFLTIMSYFQELSRKEKLRFLFLFMYSDSDDGIPLEIEVIV A polypeptide having at least 70%, optionally at least 80%, preferably at least 85%, preferably with a second amino acid sequence 90% homologous and a polypeptide having the sequence VEELLSGNPHIEKESARSIADGAMMEAASVCMGQMEPDQ corresponding to amino acids 163 to 238 of R00299_P3 with YE A single encoding R00299_P3 comprising a third amino acid sequence which is 90%, most preferably at least 95% homologous, said first, second and third amino acid sequences being in a contiguous and sequential order Detached chimeric polypeptide.

  2. The tip of R00299_P3 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence MAEKALL CPSS AGLGTW PWWVLNSAWPVLPLDV GVDWRPRGPV An isolated polypeptide encoding

  3. R00299_P3 containing a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence VEELLS GN PHIEKESAR S An isolated polypeptide encoding a tail.

Report of comparison between R00299_P3 and TESC_HUMAN 1. At least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous to a polypeptide having the sequence MAEKALLCPSSAGLGTWPWVLNSAWPVLPLAVDQGVDWRPRGPV corresponding to amino acids 1-44 of R00299_P3 1 and corresponding to amino acids 21 to 214 of TESC_HUMAN and corresponding to amino acids 45 to 238 of R00299_P3 SSDQIEQLHRRFKQLSGDQPTIRKENNNNNNPDNELPDIRNPIRSK IVRAFFDRNRNRKGPSGLADEINFEDLFLTIMSYFQELSRKEKLRFLFLFHMYDSDSDGDRIELYNV EELLSGNPHIEKESARSIADGAMMEAASVCMGQMEPDQVYEGITFEDFLKIWQGIDIETKMHVRFLNMETMALCH and and at least 90% homologous to a second amino acid sequence, wherein the first and second amino acid distribution is contiguous, and in sequential order, the isolated chimeric polypeptide coding R00299_P3.

  2. The tip of R00299_P3 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence MAEKALL CPSS AGLGTW PWWVLNSAWPVLPLDV GVDWRPRGPV An isolated polypeptide encoding

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is considered to be secreted as it is presumed that this protein has a signal peptide by one of two signal peptide estimation programs (HMM: Signal peptide, NN: NO).

  The mutein R00299_P3 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows the SNPs as shown in Table 313) It indicates whether it is known and the presence of a known SNP in the mutant protein R00299_P3 sequence supports the deduced sequence of this mutant protein of the invention).

  The mutein R00299_P3 is encoded by the following transcript: R00299_T2 (sequences shown at the end of the application). The coding portion of transcript R00299_T2 is shown in bold, starting from position 142 and ending at position 855. The transcript also has the following SNPs listed in Table 314 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein R00299_P3 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  As noted above, cluster R00299 features the twelve segments listed in Table 309 above, the sequences of which are shown at the end of the application. These segments are part of the nucleic acid sequence, which are of particular interest and are individually described herein. A description of each segment of the invention is provided herein.

  The segment cluster R00299_node_2 of the present invention is supported by three libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R00299_T2. Table 315 below describes the start and end positions of this segment on each transcript.

  The segment cluster R00299_node_30 of the present invention is supported by 75 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R00299_T2. Table 316 below describes the start and end positions of this segment on each transcript.

  According to an optional embodiment of the present invention, there is also provided a short segment associated with the above cluster. These segments are up to about 120 bp in length and are therefore included in the individual descriptions.

  The segment cluster R00299_node_10 of the present invention is supported by 46 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R00299_T2. Table 317 below describes the start and end positions of this segment on each transcript.

  The segment cluster R00299_node_14 of the present invention is supported by 61 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R00299_T2. Table 318 below describes the start and end positions of this segment on each transcript.

  The segment cluster R00299_node_15 of the invention can be found in the following transcript: R00299_T2. Table 319 below describes the start and end positions of this segment on each transcript.

  The segment cluster R00299_node_20 of the present invention is supported by 66 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R00299_T2. Table 320 below describes the start and end positions of this segment on each transcript.

  The segment cluster R00299_node_23 of the present invention is supported by 71 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R00299_T2. Table 321 below describes the start and end positions of this segment on each transcript.

  The segment cluster R00299_node_25 of the present invention is supported by 62 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R00299_T2. Table 322 below describes the start and end positions of this segment on each transcript.

  The segment cluster R00299_node_28 according to the invention can be found in the following transcript: R00299_T2. Table 323 below describes the start and end positions of this segment on each transcript.

  The segment cluster R00299_node_31 of the present invention is supported by 48 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R00299_T2. Table 324 below describes the start and end positions of this segment on each transcript.

  The segment cluster R00299_node_5 of the present invention is supported by 45 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R00299_T2. Table 325 below describes the start and end positions of this segment on each transcript.

  The segment cluster R00299_node_9 according to the invention can be found in the following transcript: R00299_T2. Table 326 below lists the start and end positions of this segment on each transcript.

  Microarray (chip) data of this gene is also available, as follows. As described above, with respect to the clusters themselves, different oligonucleotides were tested for differential expression in different disease states, in particular cancer. The following oligonucleotides were found to reach this segment (for lung cancer) (shown in Table 327).

Mutated protein alignment against previously known proteins:
Sequence name: / tmp / OleVDhrKQ0 / EjblgLomjM: Q9NWT9

Sequence documentation:

Alignment of: R00299_P3 x Q9NWT9 ..

Alignment segment 1/1:

Quality: 1162.00 Escore: 0
Matching length: 118 Total length: 118
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
45 SSDQIEQLHRRFKQLSGDQPTIRKENFNNVPDLELNPIRSKIVRAFFDNR 94
||||||||||||||||||||||||||||||||||||||||
74 SSDQIEQLHRRFKQLSGDQPTIRKENFNNVPDLELNPIRSKIVRAFFDNR 123
....
95 NLRKGPSGLADEINFEDFLTIMSYFRPIDTTM DEEQVELSRKEKLRFLF 144
||||||||||||||||||||||||||||||||||||||||
124 NLRKGPSGLADEINFEDFLTIMSYFRPIDTTM DEEQVELSRKEKLLFLF 173
.
145 MYDSDSDGRITLEEYRNV 162
|||||||||||||||||
174 MYDSDSDGRITLEEYRNV 191






Sequence name: / tmp / OleVDhrKQ0 / EjblgLomjM: TESC_HUMAN

Sequence documentation:

Alignment of: R00299_P3 x TESC_HUMAN ..

Alignment segment 1/1:

Quality: 1920.00 Escore: 0
Matching length: 194 Total length: 194
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
45 SSDQIEQLHRRFKQLSGDQPTIRKENFNNVPDLELNPIRSKIVRAFFDNR 94
||||||||||||||||||||||||||||||||||||||||
21 SSDQIEQLHRRFKQLSGDQPTIRKENFNNVPDLELNPIRSKIVRAFFDNR 70
....
95 NLRKGPSGLADEINFEDFLTIMSYFRPIDTTM DEEQVELSRKEKLRFLF 144
||||||||||||||||||||||||||||||||||||||||
71 NLRKGPSGLADEINFEDFLTIMSYFRPIDTTM DEEQVELSRKEKLLFLFH 120
....
145 MYDSDSDGRITLEEYRNVVEELLSGNPHIEKESARSIADGAMMEAASVCM 194
||||||||||||||||||||||||||||||||||||||||
121 MYDSDSDGRITLEEYRN VVEELLSGNPHIEKESARSIADGAMMEAASVCM 170
....
195 GQMEPDQVYEGITFEDFLKIWQGIDIETKMHVRFLNMETMALCH 238
||||||||||||||||||||||||||||||||||||||
171 GQMEPDQVYEGITFEDFLKIWQGIDIETKMHVRFLNMETMALCH 214

Description of cluster W60282 Cluster W60282 is characterized by one transcript and 6 segments of interest, the names of which are shown in Tables 328 and 329, respectively, and the sequence itself is shown at the end of the application. Selected protein variants are shown in Table 330.

  These sequences are known proteins kallikrein 11 precursor (SwissProt accession identifier KLKB_HUMAN, synonym EC3.4.21.-, Hippostasin, Tyrosine-like, previously known herein as a protein). A variant of (also known as a protease) (SEQ ID NO: 1428).

The protein kallikrein 11 precursor is known or considered to have the following functions: There is the possibility of a multifunctional protease. It effectively cleaves Phe-Arg-4-methylcoumaryl-7-amide (kallikrein substrate) and weakly cleaves kallikrein and other substrates of trypsin. The sequence of the protein kallikrein 11 precursor is shown at the end of the application as "kallikrein 11 precursor amino acid sequence". Localization of the protein kallikrein 11 precursor is considered secretion.

  The following GO annotation applies to previously known proteins. The following annotations have been found: proteolysis and peptide degradation that are relevant to biological processes, chymotrypsin, trypsin, serine peptidases, hydrolases that are annotations that relate to molecular function.

  GO assignments can be made at one or more http: // www. expasy. SwissProt / TremBl Protein knowledgebase available from ch / sprot / or http: // www. ncbi. nlm. nih. Depends on Locuslink available from gov / projects / LocusLink /.

  As mentioned above, cluster W60282 features one transcript as listed in Table 1 above. These transcripts encode proteins which are variants of the protein kallikrein 11 precursor. A description of each mutein of the invention is provided herein.

  The mutein W60282_PEA_1_P14 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript W60282_PEA_1_T11. An alignment to a known protein (kallikrein 11 precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between W60282_PEA_1_P14 and Q8IXD7 (SEQ ID NO: 1705) The first amino acid sequence which is at least 90% homologous to MRILQLILLALATGLVGGETRIIKGECCKPHSQPWQAALFEKTRLLCATLAPHP corresponding to amino acids 1 to 66 of Q8IXD7 and corresponding to amino acids 1 to 66 of W60282_PEA_1_P14. Said first and second amino acids comprising a second amino acid sequence which is at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous W60282_PEA_1_P14, where the arrangements are adjacent and in sequential order Code isolated chimeric polypeptide.

  2. W60282_PEA_1_P14 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence TPASHLMRQHHHH in W60282_PEA_1_P14 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein W60282_PEA_1_P14 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids and listing the other amino acids, as shown in Table 331), and the last column shows the SNPs It is shown whether it is known and the presence of a known SNP in the mutein W60282_PEA_1_P14 sequence supports the deduced sequence of this mutein of the invention).

  The mutein W60282_PEA_1_P14 is encoded by the following transcript: W60282_PEA_1_T11 (sequences shown at the end of the application). The code portion of transcript W60282_PEA_1_T11 is shown in bold, starting at position 705 and ending at position 944. The transcript also has the following SNPs listed in Table 332 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein W60282_PEA_1_P14 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  As noted above, cluster W60282 features the six segments listed in Table 329 above, the sequences of which are shown at the end of the application. These segments are part of the nucleic acid sequence, which are of particular interest and are individually described herein. A description of each segment of the invention is provided herein.

  The segment cluster W60282_PEA_1_node_10 of the present invention is supported by 45 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: W60282_PEA_1_T11. Table 333 below describes the start and end positions of this segment on each transcript.

  The segment cluster W60282_PEA_1_node_18 of the present invention is supported by 49 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: W60282_PEA_1_T11. Table 334 below describes the start and end positions of this segment on each transcript.

  The segment cluster W60282_PEA_1_node_22 of the present invention is supported by 67 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: W60282_PEA_1_T11. Table 335 below describes the start and end positions of this segment on each transcript.

  The segment cluster W60282_PEA_1_node_5 of the present invention is supported by 20 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: W60282_PEA_1_T11. Table 336 below describes the start and end positions of this segment on each transcript.

  According to an optional embodiment of the present invention, there is also provided a short segment associated with the above cluster. These segments are up to about 120 bp in length and are therefore included in the individual descriptions.

  The segment cluster W60282_PEA_1_node_21 of the present invention is supported by 48 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: W60282_PEA_1_T11. Table 337 below describes the start and end positions of this segment on each transcript.

  The segment cluster W60282_PEA_1_node_8 of the present invention is supported by 39 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: W60282_PEA_1_T11. Table 338 below describes the start and end positions of this segment on each transcript.

Mutated protein alignment against previously known proteins:
Sequence name: / tmp / rL7Wdc5hYg / eLOAfKIgqD: KLKB_HUMAN

Sequence documentation:

Alignment of: W60282_PEA_1_P14 x KLKB_HUMAN ..

Alignment segment 1/1:

Quality: 645.00 Escore: 0
Matching length: 72 Total length: 72
Matching Percent Similarity: 94.44 Matching Percent Identity: 94.44
Total Percent Similarity: 94.44 Total Percent Identity: 94.44
Gaps: 0

Alignment:
....
1 MRILQLILLALATGLVGGETRIIKKGECCKPHSQPWQAALFEKTRLLCGAT 50
||||||||||||||||||||||||||||||||||||||||
1 MRILQLILLALATGLVGGETRIIKKGECCKPHSQPWQAALFEKTRLLCGAT 50
.
51 LIAPRWLLTAAHCLKPTPASHL 72
||||||||||||||||
51 LIAPRWLLTAAHCLKPRYIVHL 72






Sequence name: / tmp / rL7Wdc5hYg / eLOAfKIgqD: Q8IXD7

Sequence documentation:

Alignment of: W60282_PEA_1_P14 x Q8IXD7 ..

Alignment segment 1/1:

Quality: 642.00 Escore: 0
Matching length: 66 Total length: 66
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MRILQLILLALATGLVGGETRIIKKGECCKPHSQPWQAALFEKTRLLCGAT 50
||||||||||||||||||||||||||||||||||||||||
1 MRILQLILLALATGLVGGETRIIKKGECCKPHSQPWQAALFEKTRLLCGAT 50
.
51 LIAPRWLLTAAHCLKP 66
||||||||||||||||
51 LIAPRWLLTAAHCLKP 66

Description of cluster Z41644 Cluster W60282 features one transcript and 21 segments of interest, the names of which are shown in Tables 339 and 340, respectively, and the sequence itself is shown at the end of the application. Selected protein variants are shown in Table 341.

  These sequences are the small inducible cytokine B14 precursor (SwissProt accession identifier SZ14_HUMAN, synonym CXCL14, also known as the chemokine BRAK), a known protein known previously as a protein previously known herein (sequence No. 1429).

  The sequence of the small protein inducible cytokine B14 precursor is shown at the end of the application as "small inducible cytokine B14 precursor amino acid sequence". Localization of the small protein inducible cytokine B14 precursor is considered to be secreted.

  The following GO annotation applies to previously known proteins. The following annotations have been found: Chemotaxis, which is an annotation related to biological processes, signaling, cell-cell signaling, an annex related to molecular function.

  GO assignments can be made at one or more http: // www. expasy. SwissProt / TremBl Protein knowledgebase available from ch / sprot / or http: // www. ncbi. nlm. nih. Depends on Locuslink available from gov / projects / LocusLink /.

  Cluster Z41644 can be used as a diagnostic marker by overexpression of transcripts of this cluster in cancer. The expression of such transcripts in normal tissues is also shown by the method previously described. The terms "numbers" in the right column of the table and the numbers on the y-axis of Fig. 27 refer to the weighted expression of ESTs in each category as "ppm" (for ESTs of a particular cluster in this category by ppm Ratio of expression to expression of all ESTs).

  In general, as shown for the histograms in FIG. 27 and Table 342, the following results were obtained. This cluster was overexpressed (at least at minimal levels) in the following pathological conditions: lung malignancy.

  As mentioned above, cluster Z41644 is characterized by one transcript as listed in Table 339 above. These transcripts encode proteins which are variants of the small protein inducible cytokine B14 precursor. A description of each mutein of the invention is provided herein.

  The mutein Z41644_PEA_1_P10 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript 41644_PEA_1_T5. An alignment to a known protein (small inducible cytokine B14 precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between Z41644_PEA_1_P10 and SZ14_HUMAN 1. MRL ILAALL LLLLY LYTARWD GSK CK CSR KEK QUICKLY RYV PK PHY EK PHE EE LYQ EQ LQ EQ LQ HEK QFK LQ KF LYQQ LYQ WKH LYQ WQH LYQH LYQ ST 第 416 LL LL LL LL A second amino acid sequence which is at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous; The first and second amino acid distribution is contiguous, and in sequential order, the isolated chimeric polypeptide coding Z41644_PEA_1_P10.

  2. Comprising a polypeptide at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 90%, most preferably at least about 95% homologous to the sequence YAPPLLTFLPTRPSCG SQDQKGPPHQVI in Z41644_PEA_1_P10, Z41644_PEA_1_P10 of An isolated polypeptide encoding a tail.

Report of the comparison between Z41644_PEA_1_P10 and Q9NS21 (SEQ ID NO: 1706) A pair of Gl7-Gl7-G7-G7: A second amino acid sequence which is at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous; And a second amino acid distribution is contiguous, and in sequential order, the isolated chimeric polypeptide coding Z41644_PEA_1_P10.

  2. Comprising a polypeptide at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 90%, most preferably at least about 95% homologous to the sequence YAPPLLTFLPTRPSCG SQDQKGPPHQVI in Z41644_PEA_1_P10, Z41644_PEA_1_P10 of An isolated polypeptide encoding a tail

Report of the comparison between Z41644_PEA_1_P10 and AAQ89265 (SEQ ID NO: 781) Corresponding to amino acids 13-107 of AAQ89265, first amino acid sequence at least 90% homologous to the corresponding MRLLAAALLLLLLALYTARVDGSKCKCSRKGPKIRYSDVKKLEMKPKYPHCEEKMVIITTKSVSRYRGQEHCLHPKLQSTKRFIKWYNAWNEKRR to amino acids 1-95 of Z41644_PEA_1_P10, the polypeptide having a sequence corresponding to YAPPLLTFLPTRPSCGSQDGKGPPHQVI to amino acid 96-123 of Z41644_PEA_1_P10 A second amino acid sequence which is at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous; The first and second amino acid distribution is contiguous, and in sequential order, the isolated chimeric polypeptide coding Z41644_PEA_1_P10.

  2. Comprising a polypeptide at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 90%, most preferably at least about 95% homologous to the sequence YAPPLLTFLPTRPSCG SQDQKGPPHQVI in Z41644_PEA_1_P10, Z41644_PEA_1_P10 of An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein Z41644_PEA_1_P10 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows SNPs as shown in Table 344) It is shown whether it is known and the presence of a known SNP in the mutant protein Z41644_PEA_1_P10 sequence supports the deduced sequence of this mutant protein of the invention).

  The mutein Z41644_PEA_1_P10 is encoded by the following transcript: Z41644_PEA_1_T5 (sequences shown at the end of the application). The code portion of transcript Z41644_PEA_1_T5 is shown in bold, starting at position 744 and ending at position 1112. The transcript also has the following SNPs listed in Table 345 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein Z41644_PEA_1_P10 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  As noted above, cluster Z41644 features the 21 segments listed in Table 340 above, the sequences of which are shown at the end of the application. These segments are part of the nucleic acid sequence, which are of particular interest and are individually described herein. A description of each segment of the invention is provided herein.

  The segment cluster Z41644_PEA_1_node_0 of the present invention is supported by 53 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: Z41644_PEA_1_T5. Table 346 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z41644_PEA_1_node_11 of the present invention is supported by nine libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: Z41644_PEA_1_T5. Table 347 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z41644_PEA_1_node_12 of the present invention is supported by six libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: Z41644_PEA_1_T5. Table 348 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z41644_PEA_1_node_15 of the present invention is supported by 23 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: Z41644_PEA_1_T5. Table 349 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z41644_PEA_1_node_20 of the present invention is supported by 260 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: Z41644_PEA_1_T5. Table 350 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z41644_PEA_1_node_24 of the present invention is supported by 185 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: Z41644_PEA_1_T5. Table 351 below describes the start and end positions of this segment on each transcript.

  According to an optional embodiment of the present invention, there is also provided a short segment associated with the above cluster. These segments are up to about 120 bp in length and are therefore included in the individual descriptions.

  The segment cluster Z41644_PEA_1_node_1 of the present invention is supported by 53 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: Z41644_PEA_1_T5. Table 352 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z41644_PEA_1_node_10 of the present invention is supported by 138 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: Z41644_PEA_1_T5. Table 353 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z41644_PEA_1_node_13 according to the invention can be found in the following transcript: Z41644_PEA_1_T5. Table 354 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z41644_PEA_1_node_16 of the present invention is supported by 152 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: Z41644_PEA_1_T5. Table 355 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z41644_PEA_1_node_17 according to the invention can be found in the following transcript: Z41644_PEA_1_T5. Table 356 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z41644_PEA_1_node_19 of the present invention is supported by 112 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: Z41644_PEA_1_T5. Table 357 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z41644_PEA_1_node_2 of the present invention is supported by 58 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: Z41644_PEA_1_T5. Table 358 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z41644_PEA_1_node_21 according to the invention can be found in the following transcript: Z41644_PEA_1_T5. Table 359 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z41644_PEA_1_node_22 of the present invention is supported by 164 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: Z41644_PEA_1_T5. Table 360 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z41644_PEA_1_node_23 of the present invention is supported by 169 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: Z41644_PEA_1_T5. Table 361 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z41644_PEA_1_node_25 of the present invention is supported by 138 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: Z41644_PEA_1_T5. Table 362 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z41644_PEA_1_node_3 of the present invention is supported by 75 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: Z41644_PEA_1_T5. Table 363 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z41644_PEA_1_node_4 of the present invention is supported by 61 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: Z41644_PEA_1_T5. Table 364 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z41644_PEA_1_node_6 of the present invention is supported by 101 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: Z41644_PEA_1_T5. Table 365 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z41644_PEA_1_node_9 of the present invention is supported by 134 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: Z41644_PEA_1_T5. Table 366 below describes the start and end positions of this segment on each transcript.

Mutated protein alignment against previously known proteins:
Sequence name: / tmp / p5SSvhT9Xp / HQeIMsUrfm: SZ14_HUMAN

Sequence documentation:

Alignment of: Z41644_PEA_1_P10 x SZ14_HUMAN ..

Alignment segment 1/1:

Quality: 953.00 Escore: 0
Matching length: 95 Total length: 95
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MRLLAAALLLLLLALYTARWDDSKCKCSKRPKIRYSDVKKLEMKPKYPH 50
||||||||||||||||||||||||||||||||||||||||
1 MRLLAAALLLLLLALYTARWDDSKCKCSKRPKIRYSDVKKLEMKPKYPH 50
....
51 CEEKMVIITTKSVSRYRGQEHCLHPKLQSTKRFIKWYNAWNEKRR 95
|||||||||||||||||||||||||||||||||||||||
51 CEEKMVIITTKSVSRYRGQEHCLHPKLQSTKRFIKWYNAWNEKRR 95






Sequence name: / tmp / p5SSvhT9Xp / HQeIMsUrfm: Q9NS21

Sequence documentation:

Alignment of: Z41644_PEA_1_P10 x Q9NS21 ..

Alignment segment 1/1:

Quality: 957.00 Escore: 0
Matching length: 96 Total length: 96
Matching Percent Similarity: 100.00 Matching Percent Identity: 98.96
Total Percent Similarity: 100.00 Total Percent Identity: 98.96
Gaps: 0

Alignment:
....
1 MRLLAAALLLLLLALYTARWDDSKCKCSKRPKIRYSDVKKLEMKPKYPH 50
||||||||||||||||||||||||||||||||||||||||
13 MRLLAAALLLLLLALYTARWDDSKCKCSKRPKIRYSDVKKLEMKPKYPH 62
....
51 CEEKMVIITTKSVSRYRGQEHCLHPKLQSTKRFIKWYNAWNEKRRY 96
|||||||||||||||||||||||||||||||||||: |
63 CEEKMVIITTKSVSRYRGQEHCLHPKLQSTKRFIKWYNAWNEKRRF 108






Sequence name: / tmp / p5SSvhT9Xp / HQeIMsUrfm: AAQ89265

Sequence documentation:

Alignment of: Z41644_PEA_1_P10 x AAQ89265 ..

Alignment segment 1/1:

Quality: 953.00 Escore: 0
Matching length: 95 Total length: 95
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MRLLAAALLLLLLALYTARWDDSKCKCSKRPKIRYSDVKKLEMKPKYPH 50
||||||||||||||||||||||||||||||||||||||||
13 MRLLAAALLLLLLALYTARWDDSKCKCSKRPKIRYSDVKKLEMKPKYPH 62
....
51 CEEKMVIITTKSVSRYRGQEHCLHPKLQSTKRFIKWYNAWNEKRR 95
|||||||||||||||||||||||||||||||||||||||
63 CEEKMVIITTKSVSRYRGQEHCLHPKLQSTKRFIKWYNAWNEKRR 107

Description of Cluster Z44808 Cluster Z44808 is characterized by 5 transcripts and 21 segments of interest, the names of which are shown in Tables 367 and 368 respectively, and the sequence itself is shown at the end of the application. Selected protein variants are shown in Table 369.

  These sequences are known proteins called SPARC-related modular calcium-binding protein 2 precursor (SwissProt accession identifier SMO2_HUMAN), which is a protein previously known herein, synonym secretory modular calcium-binding protein 2, SMOC -2, a variant of smooth muscle related protein 2, also known as SMAP-2, MSTP117) (SEQ ID NO: 1430).

  The protein SPARC related modular calcium binding protein 2 precursor is known or is considered to have the following functions: calcium binding. The sequence of the protein SPARC related modular calcium binding protein 2 precursor is shown at the end of the application as "SPARC related modular calcium binding protein 2 precursor amino acid sequence". Known polymorphisms of this sequence are shown in Table 370.

  The localization of the protein SPARC related modular calcium binding protein 2 precursor is considered to be secreted.

  Cluster Z44808 can be used as a diagnostic marker by overexpression of transcripts of this cluster in cancer. The expression of such transcripts in normal tissues is also shown by the method previously described. The terms “number” in the right column of the table and the numbers on the y-axis of FIG. 28 refer to the weighted expression of ESTs in each category as “ppm” (the ppm of ESTs of a particular cluster in this category by ppm Ratio of expression to expression of all ESTs).

  In general, as shown for the histograms in FIG. 28 and Table 371, the following results were obtained. This cluster was overexpressed (at least at minimal levels) in the following pathological conditions: colorectal cancer, lung cancer and pancreatic cancer.

  As mentioned above, cluster Z44808 is characterized by the five transcripts listed in Table 367 above. These transcripts encode a protein which is a variant of the protein SPARC related modular calcium binding protein 2 precursor. A description of each mutein of the invention is provided herein.

  The mutein Z44808_PEA_1_P5 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript Z44808_PEA_1_T4. An alignment to a known protein (SPARC related modular calcium binding protein 2 precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between Z44808_PEA_1_P5 and SMO2_HUMAN 1. Corresponding to amino acids 1 to 441 of SMO2_HUMAN, corresponding to amino acids 1 to 441 of Z44808_PEA_1_P5 MLLPQLCWLPLLAGLLPPVPAQKFSALTFLRVDQDKDKDCSLDCAGSPQKPLCASDGRTFLSRCEFQRAKCKDPQLEIAYRGNCKDVSRCVAERKYTQEQARKEFQQVFIPECNDDGTYSQVQCHSYTGYCWCVTPNGRPISGTAVAHKTPRCPGSVNEKLPQREGTGKTDDAAAPALETQPQGDEEDIASRYPTLWTEQVKSRQNKTNKNSVSSCDQEHQSALEEAKQPKNDNVVIPECAHGGLYKPVQCHPSTGYCWCVLVDTGRPIPGTSTRYE A first amino acid sequence at least 90% homologous to PikeishidienutieiarueieichiPieikeieiarudieruwaikeijiarukyuerukyujishiPijieikeikeieichiiefuerutiesubuierudieieruesutidiemubuieichieieiesudiPiesuesuesuesujiarueruesuiPidiPiesueichitieruiiarubuibuieichidaburyuwaiefukeieruerudikeienuesuesujidiaijikeikeiiaikeiPiefukeiaruefueruarukeikeiesukeiPikeikeishibuikeikeiefubuiiwaishidibuienuenudikeiesuaiesubuikyuieruemujishierujibuieiKEDGKADTKKRHTPRGHAESTSNRQ, polypeptide at least 70% with a sequence corresponding to DAMVVSSRPKATTHRKSRTLSRR to amino acid 442-464 of Z44808_PEA_1_P5, optionally at least 80%, preferably at least 85%, more preferably Is at least 90%, most preferably at least 95% homologous to the second amino acid And a sequence, the first and second amino acid distribution is contiguous, and in sequential order, the isolated chimeric polypeptide coding Z44808_PEA_1_P5.

  2. Z44808_PEA_1_P5 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence DAMVVSSRPKATTHRKSRTLSRR in Z44808_PEA_1_P5 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein Z44808_PEA_1_P5 is encoded by the following transcript: Z44808_PEA_1_T4 (sequences shown at the end of the application). The coding portion of the transcript Z44808_PEA_1_T4 is shown in bold, starting from position 586 and ending at position 1977. The transcript also has the following SNPs listed in Table 373 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein Z44808_PEA_1_P5 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein Z44808_PEA_1_P6 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript Z44808_PEA_1_T5. An alignment to a known protein (SPARC related modular calcium binding protein 2 precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between Z44808_PEA_1_P6 and SMO2_HUMAN 1. Corresponding to amino acids 1 to 428 of SMO2_HUMAN, corresponding to amino acids 1 to 428 of Z44808_PEA_1_P6 MLLPQLCWLPLLAGLLPPVPAQKFSALTFLRVDQDKDKDCSLDCAGSPQKPLCASDGRTFLSRCEFQRAKCKDPQLEIAYRGNCKDVSRCVAERKYTQEQARKEFQQVFIPECNDDGTYSQVQCHSYTGYCWCVTPNGRPISGTAVAHKTPRCPGSVNEKLPQREGTGKTDDAAAPALETQPQGDEEDIASRYPTLWTEQVKSRQNKTNKNSVSSCDQEHQSALEEAKQPKNDNVVIPECAHGGLYKPVQCHPSTGYCWCVLVDTGRPIPGTSTRYE PKCDNTARAHPAKARDLYKGRQLQGCPGAKKHEFLTSVLDALSTHDHDHAAASDPSSSSGRLSEPDPSHLEEEVHHWYFKLDKNSNSGIGKKEIKPFKFKKRKKSKPKKCVKKFVEYCDV PHI VIL MGCLA VA DG 、 に に に 44 44 44 44 44 44 Comprises a second amino acid sequence which is at least 90%, most preferably at least 95% homologous, said first and second amino acid sequences being contiguous and In consecutive order, isolated chimeric polypeptide coding Z44808_PEA_1_P6.

  2. Z44808_PEA_1_P6 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence RSKRNL in Z44808_PEA_1_P6 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein Z44808_PEA_1_P6 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows SNPs as shown in Table 374) It indicates whether it is known and the presence of a known SNP in the mutant protein Z44808_PEA_1_P6 sequence supports the deduced sequence of this mutant protein of the invention).

  The mutein Z44808_PEA_1_P6 is encoded by the following transcript: Z44808_PEA_1_T5 (sequences shown at the end of the application). The code portion of the transcript Z44808_PEA_1_T5 is shown in bold, starting at position 586 and ending at position 1887. The transcript also has the following SNPs listed in Table 375 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein Z44808_PEA_1_P6 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein Z44808_PEA_1_P7 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript Z44808_PEA_1_T9. An alignment to a known protein (SPARC related modular calcium binding protein 2 precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between Z44808_PEA_1_P7 and SMO2_HUMAN 1. Corresponding to amino acids 1 to 441 of SMO2_HUMAN, corresponding to amino acids 1 to 441 of Z44808_PEA_1_P7 MLLPQLCWLPLLAGLLPPVPAQKFSALTFLRVDQDKDKDCSLDCAGSPQKPLCASDGRTFLSRCEFQRAKCKDPQLEIAYRGNCKDVSRCVAERKYTQEQARKEFQQVFIPECNDDGTYSQVQCHSYTGYCWCVTPNGRPISGTAVAHKTPRCPGSVNEKLPQREGTGKTDDAAAPALETQPQGDEEDIASRYPTLWTEQVKSRQNKTNKNSVSSCDQEHQSALEEAKQPKNDNVVIPECAHGGLYKPVQCHPSTGYCWCVLVDTGRPIPGTSTRYE A part of the UT is not only required to be a part of one or more of the following ssssasse ssss elements such as the following elements of the sss during the sss during the sss during the sss during the event of the sss. Comprises a second amino acid sequence which is at least 90%, most preferably at least 95% homologous, 1 and a second amino acid distribution is contiguous, and in sequential order, the isolated chimeric polypeptide coding Z44808_PEA_1_P7.

  2. Z44808_PEA_1_P7 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence LLWLRGKVSFYCF in Z44808_PEA_1_P7 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein Z44808_PEA_1_P7 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing the other amino acids, and listing the other amino acids, as shown in Table 376), and the last column is the SNP It is shown whether it is known and the presence of a known SNP in the mutant protein Z44808_PEA_1_P7 sequence supports the predicted sequence of this mutant protein of the invention).

  The mutein Z44808_PEA_1_P7 is encoded by the following transcript: Z44808_PEA_1_T9 (sequences shown at the end of the application). The code portion of the transcript Z44808_PEA_1_T9 is shown in bold, starting at position 586 and ending at position 1947. The transcript also has the following SNPs listed in Table 377 (showing its position on the nucleotide sequence and listing another nucleic acid, the last column shows whether the SNP is known, mutein Z44808_PEA_1_P7 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein Z44808_PEA_1_P11 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript Z44808_PEA_1_T11. Identification of this transcript was performed using the non-EST based alternative splicing identification method described in the following cited reference: Sorek R et al. , Genome Res. (2004) 14: 1617-23. An alignment to a known protein (SPARC related modular calcium binding protein 2 precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between Z44808_PEA_1_P11 and SMO2_HUMAN 1. Corresponding to amino acids 1 - 170 of SMO2_HUMAN, first amino acid sequence at least 90% homologous to the corresponding MLLPQLCWLPLLAGLLPPVPAQKFSALTFLRVDQDKDKDCSLDCAGSPQKPLCASDGRTFLSRCEFQRAKCKDPQLEIAYRGNCKDVSRCVAERKYTQEQARKEFQQVFIPECNDDGTYSQVQCHSYTGYCWCVTPNGRPISGTAVAHKTPRCPGSVNEKLPQREGTGKT to amino acids 1 - 170 of Z44808_PEA_1_P11, corresponding to amino acids 188-446 of SMO2_HUMAN, the Z44808_PEA_1_P11 amino 171-429 Also corresponding DIASRYPTLWTEQVKSRQNKTN NSVSSCDQEHQSALEEAKQPKNDNVVIPECAHGGLYKPVQCHPSTGYCWCVLVDTGRPIPGTSTRYEQPKCDNTARAHPAKARDLYKGRQLQGCPGAKKHEFLTSVLDALSTDMVHAASDPSSSSGRLSEPDPSHTLEERVVHWYFKLLDKNSSGDIGKKEIKPFKRFLRKKSKPKKCVKKFVEYCDVNNDKSISVQELMGCLGVAKEDGKADTKKRHTPRGHAESTSNRQPRKQG and and at least 90% homologous to a second amino acid sequence, wherein the first and second amino acid distribution is contiguous, and in sequential order, the isolated chimeric polypeptide coding Z44808_PEA_1_P11.

  2. Length “n” (wherein n is at least about 10 amino acids long, optionally at least about 20 amino acids long, preferably at least about 30 amino acids long, more preferably at least about 40 amino acids long, most preferably at least about 50 amino acids long, at least two amino acids comprising TD, starting from any of the following structures: amino acids 170-x to 170, amino acids 171 + ((n-2)-x) (formula An isolated chimeric polypeptide encoding an edge portion of Z44808_PEA_1_P11, which comprises a polypeptide, wherein the sequence has a sequence terminating at 0) to n-2).

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein Z44808_PEA_1_P11 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing the other amino acids, and listing the other amino acids, as shown in Table 378), and the last column contains SNPs It indicates whether it is known and the presence of a known SNP in the mutant protein Z44808_PEA_1_P11 sequence supports the predicted sequence of this mutant protein of the invention).

  The mutein Z44808_PEA_1_P11 is encoded by the following transcript: Z44808_PEA_1_T11 (sequences shown at the end of the application). The code portion of transcript Z44808_PEA_1_T11 is shown in bold and this code portion starts at position 586 and ends at position 1872. The transcript also has the following SNPs listed in Table 379 (showing its position on the nucleotide sequence and listing another nucleic acid, the last column indicating whether the SNP is known, mutein Z44808_PEA_1_P11 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  As mentioned above, cluster Z44808 is characterized by the 21 segments listed in Table 368 above, the sequence of which is shown at the end of the application. These segments are part of the nucleic acid sequence, which are of particular interest and are individually described herein. A description of each segment of the invention is provided herein.

  The segment cluster Z44808_PEA_1_node_0 of the present invention is supported by 29 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: Z44808_PEA_1_T11, Z44808_PEA_1_T4, Z44808_PEA_1_T5, Z44808_PEA_1_T8, and Z44808_PEA_1_T9. Table 380 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z44808_PEA_1_node_16 of the present invention is supported by 39 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: Z44808_PEA_1_T11, Z44808_PEA_1_T4, Z44808_PEA_1_T5, Z44808_PEA_1_T8, and Z44808_PEA_1_T9. Table 381 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z44808_PEA_1_node_2 of the present invention is supported by 34 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: Z44808_PEA_1_T11, Z44808_PEA_1_T4, Z44808_PEA_1_T5, Z44808_PEA_1_T8, and Z44808_PEA_1_T9. Table 382 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z44808_PEA_1_node_24 of the present invention is supported by 52 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: Z44808_PEA_1_T11, Z44808_PEA_1_T4, Z44808_PEA_1_T5, Z44808_PEA_1_T8, and Z44808_PEA_1_T9. Table 383 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z44808_PEA_1_node_32 of the present invention is supported by 17 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: Z44808_PEA_1_T4 and Z44808_PEA_1_T8. Table 384 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z44808_PEA_1_node_33 of the present invention is supported by 133 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: Z44808_PEA_1_T11, Z44808_PEA_1_T4, and Z44808_PEA_1_T5. Table 385 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z44808_PEA_1_node_36 of the present invention is supported by 117 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: Z44808_PEA_1_T11, Z44808_PEA_1_T4, and Z44808_PEA_1_T5. Table 386 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z44808_PEA_1_node_37 of the present invention is supported by 120 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: Z44808_PEA_1_T11, Z44808_PEA_1_T4, and Z44808_PEA_1_T5. Table 387 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z44808_PEA_1_node_41 of the present invention is supported by two libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: Z44808_PEA_1_T9. Table 388 below describes the start and end positions of this segment on each transcript.

  According to an optional embodiment of the present invention, there is also provided a short segment associated with the above cluster. These segments are up to about 120 bp in length and are therefore included in the individual descriptions.

  The segment cluster Z44808_PEA_1_node_11 of the present invention is supported by 25 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: Z44808_PEA_1_T4, Z44808_PEA_1_T5, Z44808_PEA_1_T8, and Z44808_PEA_1_T9. Table 389 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z44808_PEA_1_node_13 of the present invention is supported by 28 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: Z44808_PEA_1_T11, Z44808_PEA_1_T4, Z44808_PEA_1_T5, Z44808_PEA_1_T8, and Z44808_PEA_1_T9. Table 390 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z44808_PEA_1_node_18 of the present invention is supported by 27 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: Z44808_PEA_1_T11, Z44808_PEA_1_T4, Z44808_PEA_1_T5, Z44808_PEA_1_T8, and Z44808_PEA_1_T9. Table 391 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z44808_PEA_1_node_22 of the present invention is supported by 33 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: Z44808_PEA_1_T11, Z44808_PEA_1_T4, Z44808_PEA_1_T5, Z44808_PEA_1_T8, and Z44808_PEA_1_T9. Table 392 below describes the start and end positions of this segment on each transcript.

  Microarray (chip) data for this segment is also available, as follows. As described above, with respect to the clusters themselves, different oligonucleotides were tested for differential expression in different disease states, in particular cancer. The following oligonucleotides were found to reach this segment (for lung cancer) (shown in Table 393).

  The segment cluster Z44808_PEA_1_node_26 of the present invention is supported by two libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: Z44808_PEA_1_T5. Table 394 below describes the start and end positions of this segment on each transcript.

  Microarray (chip) data for this segment is also available, as follows. As described above, with respect to the clusters themselves, different oligonucleotides were tested for differential expression in different disease states, in particular cancer. The following oligonucleotides were found to reach this segment (for lung cancer) (shown in Table 395).

  The segment cluster Z44808_PEA_1_node_30 of the present invention is supported by 44 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: Z44808_PEA_1_T11, Z44808_PEA_1_T4, Z44808_PEA_1_T5, Z44808_PEA_1_T8, and Z44808_PEA_1_T9. Table 396 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z44808_PEA_1_node_34 of the present invention is supported by 70 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: Z44808_PEA_1_T11, Z44808_PEA_1_T4, and Z44808_PEA_1_T5. Table 397 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z44808_PEA_1_node_35 according to the invention can be found in the following transcripts: Z44808_PEA_1_T11, Z44808_PEA_1_T4, and Z44808_PEA_1_T5. Table 398 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z44808_PEA_1_node_39 of the present invention is supported by one library. The number of libraries was determined as described above. This segment can be found in the following transcript: Z44808_PEA_1_T9. Table 399 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z44808_PEA_1_node_4 of the present invention is supported by 33 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: Z44808_PEA_1_T11, Z44808_PEA_1_T4, Z44808_PEA_1_T5, Z44808_PEA_1_T8, and Z44808_PEA_1_T9. Table 400 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z44808_PEA_1_node_6 of the present invention is supported by 30 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: Z44808_PEA_1_T11, Z44808_PEA_1_T4, Z44808_PEA_1_T5, Z44808_PEA_1_T8, and Z44808_PEA_1_T9. Table 401 below lists the start and end positions of this segment on each transcript.

  The segment cluster Z44808_PEA_1_node_8 of the present invention is supported by 25 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: Z44808_PEA_1_T11, Z44808_PEA_1_T4, Z44808_PEA_1_T5, Z44808_PEA_1_T8, and Z44808_PEA_1_T9. Table 402 below describes the start and end positions of this segment on each transcript.

Mutated protein alignment against previously known proteins:
Sequence name: / tmp / vUqLu6eAVZ / K3JDuPvaLo: SMO2_HUMAN

Sequence documentation:

Alignment of: Z44808_PEA_1_P5 x SMO2_HUMAN ..

Alignment segment 1/1:

Quality: 4440.00 Escore: 0
Matching length: 441 Total length: 441
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MLLPQLCWLPLLAGLLPPVPAQKFSALTFLRVDQDKDKDCSLDCAGSPQK 50
||||||||||||||||||||||||||||||||||||||||
1 MLLPQLCWLPLLAGLLPPVPAQKFSALTFLRVDQDKDKDCSLDCAGSPQK 50
....
51 PLCASDGRTFLSRCEFQRAKCKDPQLEIAYRGNCKDVSRCVAERKYTQEQ 100
||||||||||||||||||||||||||||||||||||||||
51 PLCASDGRTFLSRCEFQRAKCKDPQLEIAYRGNCKDVSRCVAERKYTQEQ 100
....
101 ARKEFQQVFIPECNDDGTYSQVQCHSYTGYCWCVTPNGRPISGTAVAHKT 150
||||||||||||||||||||||||||||||||||||||||
101 ARKEFQQVFIPECNDDGTYSQVQCHSYTGYCWCVTPNGRPISGTAVAHKT 150
....
151 PRCPGSVNEKLPQREGTGKTDAAAPALETQPQGDEEDIASRYPTLWTEQ 200
||||||||||||||||||||||||||||||||||||||||
151 PRCPGSVNEKLPQREGTGKTDAAAPALETQPQGDEEDIASRYPTLWTEQ 200
....
201 VKSRQNKTNKNSVSSCDQEHQSALEEAKQPKNDNV VIPECAHGGLYKPVQ 250
||||||||||||||||||||||||||||||||||||||||
201 VKSRQNKTNKNSVSSCDQEHQSALEEAKQPKNDNV VIPECAHGGLYKPVQ 250
....
251 CHPSTGYCWCVLVDTGRPIPGTSTRYEQPKCDNTARAHPAKARDLYKGRQ 300
||||||||||||||||||||||||||||||||||||||||
251 CHPSTGYCWCVLVDTGRPIPGTSTRYEQPKCDNTARAHPAKARDLYKGRQ 300
....
301 LQGCPGAKKHEFLTSVLDALSTDMVHAASDPSSSSGRLSEPDPSHTLEER 350
||||||||||||||||||||||||||||||||||||||||
301 LQGCPGAKKHEFLTSVLDALSTDMVHAASDPSSSSGRLSEPDPSHTLEER 350
....
351 VVHWYFKLLDKNSSGDGIKKEIKPFKRFLRKKSKPKKCVKKFVEYCDVNN 400
||||||||||||||||||||||||||||||||||||||||
351 VVHWYFKLLDKNSSGDGIKKEIKPFKRFLRKKSKPKKCVKKFVEYCDVNN 400
....
401 DKSISVQELMGCLGVAKEDGKADTKKRHTPRGHAESTSNRQ 441
||||||||||||||||||||||||||||||||||||
401 DKSISVQELMGCLGVAKEDGKADTKKRHTPRGHAESTSNRQ 441






Sequence name: / tmp / QSUNfTsJ5y / kLOw5Vb6SD: SMO2_HUMAN

Sequence documentation:

Alignment of: Z44808_PEA_1_P6 x SMO2_HUMAN ..

Alignment segment 1/1:

Quality: 4310.00 Escore: 0
Matching length: 428 Total length: 428
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MLLPQLCWLPLLAGLLPPVPAQKFSALTFLRVDQDKDKDCSLDCAGSPQK 50
||||||||||||||||||||||||||||||||||||||||
1 MLLPQLCWLPLLAGLLPPVPAQKFSALTFLRVDQDKDKDCSLDCAGSPQK 50
....
51 PLCASDGRTFLSRCEFQRAKCKDPQLEIAYRGNCKDVSRCVAERKYTQEQ 100
||||||||||||||||||||||||||||||||||||||||
51 PLCASDGRTFLSRCEFQRAKCKDPQLEIAYRGNCKDVSRCVAERKYTQEQ 100
....
101 ARKEFQQVFIPECNDDGTYSQVQCHSYTGYCWCVTPNGRPISGTAVAHKT 150
||||||||||||||||||||||||||||||||||||||||
101 ARKEFQQVFIPECNDDGTYSQVQCHSYTGYCWCVTPNGRPISGTAVAHKT 150
....
151 PRCPGSVNEKLPQREGTGKTDAAAPALETQPQGDEEDIASRYPTLWTEQ 200
||||||||||||||||||||||||||||||||||||||||
151 PRCPGSVNEKLPQREGTGKTDAAAPALETQPQGDEEDIASRYPTLWTEQ 200
....
201 VKSRQNKTNKNSVSSCDQEHQSALEEAKQPKNDNV VIPECAHGGLYKPVQ 250
||||||||||||||||||||||||||||||||||||||||
201 VKSRQNKTNKNSVSSCDQEHQSALEEAKQPKNDNV VIPECAHGGLYKPVQ 250
....
251 CHPSTGYCWCVLVDTGRPIPGTSTRYEQPKCDNTARAHPAKARDLYKGRQ 300
||||||||||||||||||||||||||||||||||||||||
251 CHPSTGYCWCVLVDTGRPIPGTSTRYEQPKCDNTARAHPAKARDLYKGRQ 300
....
301 LQGCPGAKKHEFLTSVLDALSTDMVHAASDPSSSSGRLSEPDPSHTLEER 350
||||||||||||||||||||||||||||||||||||||||
301 LQGCPGAKKHEFLTSVLDALSTDMVHAASDPSSSSGRLSEPDPSHTLEER 350
....
351 VVHWYFKLLDKNSSGDGIKKEIKPFKRFLRKKSKPKKCVKKFVEYCDVNN 400
||||||||||||||||||||||||||||||||||||||||
351 VVHWYFKLLDKNSSGDGIKKEIKPFKRFLRKKSKPKKCVKKFVEYCDVNN 400
.
401 DKSIS VQELMGCLGVAKEDGKADTKKRH 428
||||||||||||||||||||||||||
401 DKSIS VQELMGCLGVAKEDGKADTKKRH 428






Sequence name: / tmp / MZVdR4PVdM / 5uN8RwViJ1: SMO2_HUMAN

Sequence documentation:

Alignment of: Z44808_PEA_1_P7 x SMO2_HUMAN ..

Alignment segment 1/1:

Quality: 4440.00 Escore: 0
Matching length: 441 Total length: 441
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MLLPQLCWLPLLAGLLPPVPAQKFSALTFLRVDQDKDKDCSLDCAGSPQK 50
||||||||||||||||||||||||||||||||||||||||
1 MLLPQLCWLPLLAGLLPPVPAQKFSALTFLRVDQDKDKDCSLDCAGSPQK 50
....
51 PLCASDGRTFLSRCEFQRAKCKDPQLEIAYRGNCKDVSRCVAERKYTQEQ 100
||||||||||||||||||||||||||||||||||||||||
51 PLCASDGRTFLSRCEFQRAKCKDPQLEIAYRGNCKDVSRCVAERKYTQEQ 100
....
101 ARKEFQQVFIPECNDDGTYSQVQCHSYTGYCWCVTPNGRPISGTAVAHKT 150
||||||||||||||||||||||||||||||||||||||||
101 ARKEFQQVFIPECNDDGTYSQVQCHSYTGYCWCVTPNGRPISGTAVAHKT 150
....
151 PRCPGSVNEKLPQREGTGKTDAAAPALETQPQGDEEDIASRYPTLWTEQ 200
||||||||||||||||||||||||||||||||||||||||
151 PRCPGSVNEKLPQREGTGKTDAAAPALETQPQGDEEDIASRYPTLWTEQ 200
....
201 VKSRQNKTNKNSVSSCDQEHQSALEEAKQPKNDNV VIPECAHGGLYKPVQ 250
||||||||||||||||||||||||||||||||||||||||
201 VKSRQNKTNKNSVSSCDQEHQSALEEAKQPKNDNV VIPECAHGGLYKPVQ 250
....
251 CHPSTGYCWCVLVDTGRPIPGTSTRYEQPKCDNTARAHPAKARDLYKGRQ 300
||||||||||||||||||||||||||||||||||||||||
251 CHPSTGYCWCVLVDTGRPIPGTSTRYEQPKCDNTARAHPAKARDLYKGRQ 300
....
301 LQGCPGAKKHEFLTSVLDALSTDMVHAASDPSSSSGRLSEPDPSHTLEER 350
||||||||||||||||||||||||||||||||||||||||
301 LQGCPGAKKHEFLTSVLDALSTDMVHAASDPSSSSGRLSEPDPSHTLEER 350
....
351 VVHWYFKLLDKNSSGDGIKKEIKPFKRFLRKKSKPKKCVKKFVEYCDVNN 400
||||||||||||||||||||||||||||||||||||||||
351 VVHWYFKLLDKNSSGDGIKKEIKPFKRFLRKKSKPKKCVKKFVEYCDVNN 400
....
401 DKSISVQELMGCLGVAKEDGKADTKKRHTPRGHAESTSNRQ 441
||||||||||||||||||||||||||||||||||||
401 DKSISVQELMGCLGVAKEDGKADTKKRHTPRGHAESTSNRQ 441






Sequence name: / tmp / 3fGVxqLloe / J5mQduAd0F: SMO2_HUMAN

Sequence documentation:

Alignment of: Z44808_PEA_1_P11 x SMO2_HUMAN ..

Alignment segment 1/1:

Quality: 4228.00 Escore: 0
Matching length: 429 Total length: 446
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 96.19 Total Percent Identity: 96.19
Gaps: 1

Alignment:
....
1 MLLPQLCWLPLLAGLLPPVPAQKFSALTFLRVDQDKDKDCSLDCAGSPQK 50
||||||||||||||||||||||||||||||||||||||||
1 MLLPQLCWLPLLAGLLPPVPAQKFSALTFLRVDQDKDKDCSLDCAGSPQK 50
....
51 PLCASDGRTFLSRCEFQRAKCKDPQLEIAYRGNCKDVSRCVAERKYTQEQ 100
||||||||||||||||||||||||||||||||||||||||
51 PLCASDGRTFLSRCEFQRAKCKDPQLEIAYRGNCKDVSRCVAERKYTQEQ 100
....
101 ARKEFQQVFIPECNDDGTYSQVQCHSYTGYCWCVTPNGRPISGTAVAHKT 150
||||||||||||||||||||||||||||||||||||||||
101 ARKEFQQVFIPECNDDGTYSQVQCHSYTGYCWCVTPNGRPISGTAVAHKT 150
....
151 PRCPGSGNEKLPQREGTGKT .............. DIASRYPTLWTEQ 183
|||||||||||||||||||||||||||||
151 PRCPGSVNEKLPQREGTGKTDAAAPALETQPQGDEEDIASRYPTLWTEQ 200
....
184 VKSRQNKTNKNSVSSCDQEHQSALEEAKQPKNDNV VIPECAHGGLYKPVQ 233
||||||||||||||||||||||||||||||||||||||||
201 VKSRQNKTNKNSVSSCDQEHQSALEEAKQPKNDNV VIPECAHGGLYKPVQ 250
....
234 CHPSTGYCWCVLVDTGRPIPGTSTRYEQPKCDNTARAHPAKARDLYKGRQ 283
||||||||||||||||||||||||||||||||||||||||
251 CHPSTGYCWCVLVDTGRPIPGTSTRYEQPKCDNTARAHPAKARDLYKGRQ 300
....
284 LQGCPGAKKHEFLTSV LDALSDLM VHAASDPSSSSGRLSEPDPSHTLEER 333
||||||||||||||||||||||||||||||||||||||||
301 LQGCPGAKKHEFLTSVLDALSTDMVHAASDPSSSSGRLSEPDPSHTLEER 350
....
334 VVHWYFKLLDKNSSGDGIKKEIKPFKRFLRKKSKPKKCVKKFVEYCDVNN 383
||||||||||||||||||||||||||||||||||||||||
351 VVHWYFKLLDKNSSGDGIKKEIKPFKRFLRKKSKPKKCVKKFVEYCDVNN 400
....
384 DKSISVQELMGCLGVAKEDGKADTKKRHTPRGHAESTSNRQPQG 429
|||||||||||||||||||||||||||||||||||||||
401 DKSISVQELMGCLGVAKEDGKADTKKRHTPRGHAESTSNRQPQG 446

Expression of SMO2_HUMAN SPARC related modular calcium binding protein 2 precursor Z44808 transcript detectable by an amplicon as shown in SEQ ID NO: Z44808junc8-11 in normal and cancerous lung tissues junc8-11, Z44808junc8-11 amplicon (SEQ ID NO: 1651) SMO2_HUMAN SPARC related modular calcium binding protein 2 precursor (secretory modular calcium binding protein 2) (SMOC-2) (SMOC-2) detectable by Z44808 junc 8-11F (SEQ ID NO: 1649) and Z44808 junc 8-11 R (SEQ ID NO: 1650) primers Muscle related protein 2) Transcript expression was measured by real time PCR. In parallel, four housekeeping genes-PBGD (GenBank Accession No. BC019323, Amplicon – PBGD-Amplicon, SEQ ID No. 334), HPRT1 (GenBank Accession No. NM_000194, Amplicon – HPRT1- Amplicons, SEQ ID NO: 1297), Ubiquitin (GenBank Accession No. BC000449, Amplicon – Ubiquitin-Amplicon SEQ ID NO: 328), and SDHA (GenBank Accession No. NM_004168, Amplicon – SDHA-Amplicon SEQ ID NO: 331) was similarly measured. For each RT sample, the expression of the amplicon was normalized to the geometric mean of the housekeeping gene dose. The normalized amount of each RT sample is the center of the amount of normal postmortem (PM) samples (sample numbers 47-50, 90-93, 96-99 above, Table 2, "tissue samples in the test panel") Divide by the value to obtain the magnification of the upregulation of each sample relative to the median of normal PM samples.

  FIG. 29 is a histogram showing over expression of the SMO2_HUMAN SPARC related modular calcium binding protein 2 precursor transcript in several cancerous lung samples compared to normal samples.

  As evident from FIG. 29, the expression of SMO2_HUMAN SPARC related modular calcium binding protein 2 precursor transcripts detectable by the above amplicon in several cancer samples is a non-cancerous sample (sample nos. 47-50, 90) ~ 93, 96-99, Table 2, "Tissue samples in test panel" was significantly higher. Apparently, at least 5-fold overexpression was found in 2 out of 15 adenocarcinoma samples and 3 out of 8 small cell carcinoma samples.

  Primer pairs are also optionally and preferably included within the scope of the present invention, for example, in the above experiments the following primers were used only as non-limiting examples of suitable primer pairs: Z44808junc8-11F forward primer and Z44808 junc 8-11 R reverse primer.

  The present invention also preferably includes any amplicon obtained by use of any suitable primer pair (e.g. in the above experiments) and obtained the following amplicons only as a non-limiting illustration of a suitable amplicon : Z44808 junc 8-11.

Forward primer (SEQ ID NO: 1649): GAAGGCACAGGAAAAACAGATATTG
Reverse primer (SEQ ID NO: 1650): TGGTGCTCTTGGTCACAGAGAT
Amplicon (SEQ ID NO: 1651): GAAGGCACAGGAAAAACGATATTGCATCACGTTACCCTACCCTTTGGACTGAACAGGTTAAAAGTCGGCAGAACAAAACCAATAAGAATTCAGTGTGATCCTGTGACCAAGAGCACCA

SMO2_HUMAN SPARC related modular calcium binding protein 2 precursor (secretory modular calcium binding protein 2) (SMOC-2) (smooth muscle related protein 2) Z44808 detectable by the amplicon shown in the sequence name Z44808 junc 8-11 in different normal tissues Transcript expression Z44808junc8-11 amplicon (SEQ ID NO: 1651) and SMO2_HUMAN SPARC related modular calcium binding protein 2 precursor detectable by the primers Z44808junc 8-11F (SEQ ID NO: 1649) and Z44808 junc 8-11R (SEQ ID NO: 1650) (secretory property Generation of modular calcium binding protein 2) (SMOC-2) (smooth muscle associated protein 2) Z44808 transcript The expression was measured by real time PCR. In parallel, four housekeeping genes-RPL19 (GenBank Accession No. NM_000981, RPL19 amplicon, SEQ ID No. 1630), TATA box (GenBank Accession No. NM_003194, TATA amplicon, SEQ ID No. 1633), ubiquitin (GenBank Accession No. BC000449, amplicon – ubiquitin-amplicon, SEQ ID NO: 328), and SDHA (GenBank accession number NM_004168, amplicon – SDHA-amplicon, SEQ ID NO: 331) were similarly measured. For each RT sample, the expression of the amplicon was normalized to the geometric mean of the housekeeping gene dose. The normalized amount of each RT sample was divided by the median of the amounts of ovary samples (Sample Nos. 18-20, Table 3) to obtain the relative expression value of each sample relative to the median of the ovary samples.

Primer:
Forward primer (SEQ ID NO: 1649): GAAGGCACAGGAAAAACAGATATTG
Reverse primer (SEQ ID NO: 1650): TGGTGCTCTTGGTCACAGAGAT
Amplicon (SEQ ID NO: 1651): GAAGGCACAGGAAAAACGATATTGCATCACGTTACCCTACCCTTTGGACTGAACAGGTTAAAAGTCGGCAGAACAAAACCAATAAGAATTCAGTGTGATCCTGTGACCAAGAGCACCA

  The results are shown in FIG. 18, which shows that SMO2_HUMAN SPARC related modular calcium binding protein 2 precursor (secretory modular calcium binding protein 2) detectable by an amplicon shown in the sequence name Z44808 junc 8-11 in different normal tissues (SMOC- 2) (Smooth muscle related protein 2) The expression of Z44808 is shown.

Description of cluster AA161187 Cluster AA161187 is characterized by 7 transcripts and 20 segments of interest, the names of which are shown in Tables 403 and 404, respectively, and the sequences themselves are shown at the end of the application. Selected protein variants are shown in Table 405.

  These sequences are known proteins Testisin precursor (SwissProt accession identifier TEST_HUMAN), which is a known protein, previously known herein as protein, with the synonym EC 3.4.21. Eosinophil serine protease 1, also known as ESP-1, UNQ266 / PRO303 (SEQ ID NO 1431).

  The protein testerin precursor is known or considered to have the following functions: It can modulate the proteolytic events associated with testicular germ cell maturation. The sequence of the proteinessicin precursor is shown at the end of the application as "testicin precursor amino acid sequence". The localization of the protein testerin precursor is thought to be membrane bound by the GPI-anchor.

  The following GO annotation applies to previously known proteins. The following annotations were found: serine type peptidases that are related to molecular function, membrane fractions that are annotations related to cellular components, cytoplasm, plasma membrane.

  GO assignments can be made at one or more http: // www. expasy. SwissProt / TremBl Protein knowledgebase available from ch / sprot / or http: // www. ncbi. nlm. nih. Depends on Locuslink available from gov / projects / LocusLink /.

  Cluster AA161187 can be used as a diagnostic marker by overexpression of transcripts of this cluster in cancer. The expression of such transcripts in normal tissues is also shown by the method previously described. The terms “number” in the left column of the table and the number on the y-axis of FIG. 30 refer to the weighted expression of ESTs in each category as “ppm” (the ppm of ESTs of a particular cluster in this category by ppm Ratio of expression to expression of all ESTs).

  In general, as shown for the histograms in FIG. 30 and Table 406, the following results were obtained. This cluster was overexpressed (at least at minimal levels) in the following pathological conditions: malignant brain tumors, epithelial malignancies, and a mixture of malignancies from different tissues.

  As mentioned above, cluster AA161187 is characterized by the seven transcripts listed in Table 403 above. These transcripts encode a protein that is a mutated form of the protein testerin precursor. A description of each mutein of the invention is provided herein.

  The mutein AA161187_P1 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript AA161187_T0. The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is considered to be secreted, as both signal peptide estimation programs presume this protein to have a signal peptide.

  The mutein AA161187_P1 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows SNPs as shown in Table 408) It is indicated whether it is known and the presence of a known SNP in the mutant protein AA161187_P1 sequence supports the deduced sequence of this mutant protein according to the invention).

  The mutein AA161187_P1 is encoded by the following transcript: AA161187_T0 (sequences shown at the end of the application). The code portion of transcript AA161187_T0 is shown in bold and this code portion starts at position 107 and ends at position 1048. The transcript also has the following SNPs listed in Table 409 (showing its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein AA161187_P1 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein AA161187_P6 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript AA161187_T7. An alignment to a known protein (testicin precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between AA161187_P6 and TEST_HUMAN 1. A first amino acid sequence that is at least 70%, optionally at least 80%, preferably at least 85%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous to HTREGTLGGQKRAFPDGVEGEKGRAWGAASRGSAVPLTIR corresponding to amino acids 1-42 of AA161187_P6 , Corresponding to amino acids 31 to 314 of TEST_HUMAN and corresponding to amino acids 43 to 326 of AA 161 187 _P 6 GPCGRRVITSRIVGGEDAELGRWPWQGSLLRWDSHVCGVSLLSHRWALTAAHCFETYSDLSDPSGWMQFGSMTSFLSQAYTRYFVSNIYLSPRYLGNSPYDIALVKLSAPVTYTKHIQ ASTFEFENRTDCWVTGWGYIKEDEALPSPHTLQEVQVAIINNSMCNHLFLKYSFRKDIFGDMVCAGNAQGGKDACFGDSGGPLACNKNGLWYQIGVVSWGVGCGRPNRPGVYTNISHHFEWIQKLMAQSGMSQPDPSWPLLFFPLLWALPLLGPV and and at least 90% homologous to a second amino acid sequence, the first amino acid sequence and a second amino acid sequence, contiguous and in sequential order, the isolated chimeric polypeptide coding AA161187_P6.

  2. The tip of AA161187_P6 comprising a polypeptide that is at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence HTREGTLGGQKRAFPDGVEGEKGRAWGAASRGSAVPLTIR of AA161187_P6 An isolated polypeptide encoding

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: membrane. Although protein localization is a partial protein, it is considered to be a membrane because both transmembrane domain estimation programs presume that this protein has a transmembrane domain.

  The mutein AA161187_P6 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows SNPs as shown in Table 410) It is shown whether it is known and the presence of a known SNP in the mutant protein AA161187_P6 sequence supports the deduced sequence of this mutant protein of the invention).

  The glycosylation sites of mutant protein AA161187_P6 compared to the known protein testerin precursor are shown in Table 411 (showing its position on the amino acid sequence in the first column, the second column has a glycosylation site in the mutant protein) The last column indicates whether this position differs on the mutant protein).

  The mutein AA161187_P6 is encoded by the following transcript: AA161187_T7 (sequences shown at the end of the application). The coding portion of transcript AA161187 T7 is shown in bold and this coding portion starts from position 1 and ends at position 979. The transcript also has the following SNPs listed in Table 412 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein AA161187_P6 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein AA161187_P13 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript AA161187_T15. An alignment to a known protein (testicin precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between AA161187_P13 and TEST_HUMAN 1. Corresponding to amino acids 1-183 of TEST_HUMAN, the polypeptide having a MGARGALLLALLLARAGLRKPESQEAAPLSGPCGRRVITSRIVGGEDAELGRWPWQGSLRLWDSHVCGVSLLSHRWALTAAHCFETYSDLSDPSGWMVQFGQLTSMPSFWSLQAYYTRYFVSNIYLSPRYLGNSPYDIALVKLSAPVTYTKHIQPICLQASTFEFENRTDCWVTGWGYIKEDE corresponding to amino acids 1-183 of AA161187_P13 the first amino acid sequence at least 90% homologous, sequences corresponding to GSSGRHHKQLYVQPPLPQVQFPQGHLWRHG to amino acid 184-213 of AA161187_P13 Less Said first amino acid sequence and the second amino acid sequence both at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous; An isolated chimeric polypeptide encoding AA161187_P13, wherein the two amino acid sequences are in contiguous and sequential order.

  2. AA161187_P13 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence GSSGRHHKQLYVQPPLPQVQFPQGHLWRH in AA161187_P13, An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein AA161187_P13 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing the other amino acids, and listing the other amino acids, as shown in Table 413) It is indicated whether it is known and the presence of a known SNP in the mutein AA161187_P13 sequence supports the deduced sequence of this mutein of the invention).

  The glycosylation sites of mutant protein AA161187_P13 compared to the known protein testerin precursor are shown in Table 414 (showing its position on the amino acid sequence in the first column, the second column has a glycosylation site in the mutant protein) The last column indicates whether this position differs on the mutant protein).

  The mutein AA161187_P13 is encoded by the following transcript: AA161187_T15 (sequences shown at the end of the application). The code portion of transcript AA161187_T15 is shown in bold and this code portion starts at position 107 and ends at position 745. The transcript also has the following SNPs listed in Table 415 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein AA161187_P13 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein AA161187_P14 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript AA161187_T16. An alignment to a known protein (testicin precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between AA161187_P14 and TEST_HUMAN 1. Corresponding to amino acids 1-183 of TEST_HUMAN, first amino acid sequence at least 90% homologous to the corresponding MGARGALLLALLLARAGLRKPESQEAAPLSGPCGRRVITSRIVGGEDAELGRWPWQGSLRLWDSHVCGVSLLSHRWALTAAHCFETYSDLSDPSGWMVQFGQLTSMPSFWSLQAYYTRYFVSNIYLSPRYLGNSPYDIALVKLSAPVTYTKHIQPICLQASTFEFENRTDCWVTGWGYIKEDE to amino acids 1-183 of AA161187_P14, corresponding to amino acids 184-307 of AA161187_P14 sequence GCCLSPSHYRPHSTAISPHPPGSSGRHHKQLYVQPPLPQVQFP A polypeptide having at least 70%, optionally at least 80%, preferably at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous to the second amino acid sequence An isolated chimeric polypeptide encoding AA161187_P14, wherein the amino acid sequence of 1 and the second amino acid sequence are in contiguous and sequential order.

  2. At least 70% of the sequence GCCLSPHYSHRIPISPHPPGSGGHHQQPPQQQQFPQGHLWRHGLCLCWQPRREGCLCPHHQPRKASCVPVPYLTMPTPGGGDCCPQGEEEDVHPVIPAP in the sequence of AA161187_P14, optionally at least about 80%, preferably at least about 70%, for example. An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein AA161187_P14 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids and listing the other amino acids, as shown in Table 416), and the last column shows SNPs It is indicated whether it is known and the presence of a known SNP in the mutant protein AA161187_P14 sequence supports the deduced sequence of this mutant protein of the invention).

  The glycosylation sites of mutant protein AA161187_P14 compared to the known protein testerin precursor are shown in Table 417 (showing its position on the amino acid sequence in the first column, the second column has a glycosylation site in the mutant protein) The last column indicates whether this position differs on the mutant protein).

  The mutein AA161187_P14 is encoded by the following transcript: AA161187_T16 (sequences shown at the end of the application). The coding portion of transcript AA161187_T16 is shown in bold, starting at position 107 and ending at position 1027. The transcript also has the following SNPs listed in Table 418 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein AA161187_P14 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein AA161187_P18 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript AA161187_T20. An alignment to a known protein (testicin precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between AA161187_P18 and TEST_HUMAN 1. At least 70%, optionally at least 80%, preferably at least 85%, preferably at least 90%, more preferably at least 90%, most preferably at least 95% homologous to the polypeptide having the sequence HTREGTLGGQKRAFPDGVEGERGGRAWGAASRGSAVPLTIR corresponding to amino acids 1-42 of AA161187_P18 1, an amino acid sequence corresponding to amino acids 31 to 86 of TEST_HUMAN and corresponding to amino acids 43 to 98 of AA161187_P18. AA161187_P1 A corresponding DLCSPS GWFQFQQQHQFSMQFHQHQFQQFHQHQHQHQHQFSMQFHQFHQFHQFSMQFHQFHQFH. , Preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous to a fourth amino acid sequence Seen, the first amino acid sequence, the second amino acid sequence, a third amino acid sequence, and the fourth amino acid sequence is adjacent, and in sequential order, the isolated chimeric polypeptide coding AA161187_P18.

  2. The tip of AA161187_P18, comprising a polypeptide that is at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence HTREGTLGGQKRAFPDGVEGEKGRAWGAASRGSAVPLTIR of AA161187_P18 An isolated polypeptide encoding

  3. Length “n” (wherein n is at least about 10 amino acids long, optionally at least about 20 amino acids long, preferably at least about 30 amino acids long, more preferably at least about 40 amino acids long, most preferably at least about 50 amino acids long, at least two amino acids comprising TD, starting from any of the following structures: amino acids nos. 98-x to 98, amino acids nos. 99 + ((n-2)-x) (formula An isolated chimeric polypeptide encoding an edge portion of AA161187_P18, comprising a polypeptide having a sequence terminating in: x) varying from 0 to n-2).

  AA161187_P18 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence VSVPATTSPSGKHPVSLCL1 in AA161187_P18 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: membrane. Although protein localization is a partial protein, it is considered to be a membrane because both transmembrane domain estimation programs presume that this protein has a transmembrane domain.

  The mutein AA161187_P18 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows SNPs as shown in Table 419) It is indicated whether it is known and the presence of a known SNP in the mutant protein AA161187_P18 sequence supports the deduced sequence of this mutant protein of the invention).

  The glycosylation sites of mutant protein AA161187_P18 compared to the known protein testerin precursor are shown in Table 420 (showing its position on the amino acid sequence in the first column, the second column has a glycosylation site in the mutant protein) The last column indicates whether this position differs on the mutant protein).

  The mutein AA161187_P18 is encoded by the following transcript: AA161187_T20 (sequences shown at the end of the application). The coding portion of transcript AA161187_T20 is shown in bold and this coding portion starts from position 1 and ends at position 796. The transcript also has the following SNPs listed in Table 421 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein AA161187_P18 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein AA161187_P19 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript AA161187_T21. An alignment to a known protein (testicin precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between AA161187_P19 and TEST_HUMAN 1. Corresponding to amino acids 1-183 of TEST_HUMAN, the polypeptide having a MGARGALLLALLLARAGLRKPESQEAAPLSGPCGRRVITSRIVGGEDAELGRWPWQGSLRLWDSHVCGVSLLSHRWALTAAHCFETYSDLSDPSGWMVQFGQLTSMPSFWSLQAYYTRYFVSNIYLSPRYLGNSPYDIALVKLSAPVTYTKHIQPICLQASTFEFENRTDCWVTGWGYIKEDE corresponding to amino acids 1-183 of AA161187_P19 the first amino acid sequence at least 90% homologous, sequences corresponding to DKRTQ to amino acid 184-188 of AA161187_P19 And at least 70%, optionally at least 80%, preferred Comprises a second amino acid sequence which is at least 85%, more preferably at least 90%, most preferably at least 95% homologous, the first amino acid sequence and the second amino acid sequence being adjacent and contiguous order An isolated chimeric polypeptide encoding AA161187_P19, wherein

  2. AA161187_P19 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence DKRTQ in AA161187_P19 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein AA161187_P19 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows SNPs as shown in Table 422) It is shown whether it is known and the presence of a known SNP in the mutant protein AA161187_P19 sequence supports the deduced sequence of this mutant protein of the invention).

  The glycosylation sites of mutant protein AA161187_P19 compared to the known protein testerin precursor are shown in Table 423 (showing its position on the amino acid sequence in the first column, the second column has a glycosylation site in the mutant protein) The last column indicates whether this position differs on the mutant protein).

  The mutein AA161187_P19 is encoded by the following transcript: AA161187_T21 (sequences shown at the end of the application). The code portion of transcript AA161187_T21 is shown in bold and this code portion starts at position 107 and ends at position 670. The transcript also has the following SNPs listed in Table 424 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein AA161187_P19 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  As noted above, cluster AA 161 187 features the twenty segments listed in Table 404 above, the sequences of which are shown at the end of the application. These segments are part of the nucleic acid sequence, which are of particular interest and are individually described herein. A description of each segment of the invention is provided herein.

  The segment cluster AA161187_node_0 of the present invention is supported by 21 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: AA161187_T0, AA161187_T15, AA161187_T16, AA161187_T21, and AA161187_T22. Table 425 below describes the start and end positions of this segment on each transcript.

  The segment cluster AA161187_node_6 of the present invention is supported by three libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: AA161187_T7 and AA161187_T20. Table 426 below describes the start and end positions of this segment on each transcript.

  The segment cluster AA161187_node_14 of the present invention is supported by 35 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: AA161187_T0, AA161187_T7, AA161187_T15, AA161187_T16, AA161187_T20, AA161187_T21, and AA161187_T22. Table 427 below describes the start and end positions of this segment on each transcript.

  The segment cluster AA161187_node_16 of the present invention is supported by two libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: AA161187_T22. Table 428 below describes the start and end positions of this segment on each transcript.

  The segment cluster AA161187_node_25 of the present invention is supported by 13 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: AA161187_T16 and AA161187_T20. Table 429 below describes the start and end positions of this segment on each transcript.

  Microarray (chip) data for this segment is also available, as follows. As described above, with respect to the clusters themselves, different oligonucleotides were tested for differential expression in different disease states, in particular cancer. The following oligonucleotides were found to reach this segment (for lung cancer) (shown in Table 430).

  The segment cluster AA161187_node_26 of the present invention is supported by 39 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: AA161187_T0, AA161187_T7, AA161187_T15, AA161187_T16, and AA161187_T20. Table 431 below describes the start and end positions of this segment on each transcript.

  The segment cluster AA161187_node_28 of the present invention is supported by 4 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: AA161187_T21. Table 432 below describes the start and end positions of this segment on each transcript.

  According to an optional embodiment of the present invention, there is also provided a short segment associated with the above cluster. These segments are up to about 120 bp in length and are therefore included in the individual descriptions.

  The segment cluster AA161187_node_4 of the present invention is supported by 22 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: AA161187_T0, AA161187_T7, AA161187_T15, AA161187_T16, AA161187_T21, and AA161187_T22. Table 433 below describes the start and end positions of this segment on each transcript.

  The segment cluster AA161187_node_7 of the invention can be found in the following transcripts: AA161187_T7 and AA161187_T20. Table 434 below describes the start and end positions of this segment on each transcript.

  The segment cluster AA161187_node_8 of the present invention is supported by 23 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: AA161187_T0, AA161187_T7, AA161187_T15, AA161187_T16, AA161187_T20, AA161187_T21, and AA161187_T22. Table 435 below describes the start and end positions of this segment on each transcript.

  The segment cluster AA161187_node_9 of the present invention is supported by 24 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: AA161187_T0, AA161187_T7, AA161187_T15, AA161187_T16, AA161187_T20, AA161187_T21, and AA161187_T22. Table 436 below describes the start and end positions of this segment on each transcript.

  The segment cluster AA161187_node_10 of the present invention is supported by 25 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: AA161187_T0, AA161187_T7, AA161187_T15, AA161187_T16, AA161187_T20, AA161187_T21, and AA161187_T22. Table 437 below describes the start and end positions of this segment on each transcript.

  The segment cluster AA161187_node_12 according to the invention can be found in the following transcripts: AA161187_T0, AA161187_T7, AA161187_T15, AA161187_T16, AA161187_T21, and AA161187_T22. Table 438 below describes the start and end positions of this segment on each transcript.

  The segment cluster AA161187_node_13 of the present invention is supported by 25 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: AA161187_T0, AA161187_T7, AA161187_T15, AA161187_T16, AA161187_T20, AA161187_T21, and AA161187_T22. Table 439 below describes the start and end positions of this segment on each transcript.

  The segment cluster AA161187_node_19 of the present invention is supported by four libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: AA161187_T16. Table 440 below describes the start and end positions of this segment on each transcript.

  The segment cluster AA161187_node_20 of the present invention is supported by 28 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: AA161187_T0, AA161187_T7, AA161187_T16, and AA161187_T20. Table 441 below describes the start and end positions of this segment on each transcript.

  The segment cluster AA161187_node_21 of the present invention is supported by 31 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: AA161187_T0, AA161187_T7, AA161187_T15, AA161187_T16, and AA161187_T20. Table 442 below describes the start and end positions of this segment on each transcript.

  The segment cluster AA161187_node_22 of the present invention is supported by 34 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: AA161187_T0, AA161187_T7, AA161187_T15, AA161187_T16, and AA161187_T20. Table 443 below describes the start and end positions of this segment on each transcript.

  The segment cluster AA161187_node_23 of the present invention is supported by 31 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: AA161187_T0, AA161187_T7, AA161187_T16, and AA161187_T20. Table 444 below describes the start and end positions of this segment on each transcript.

  The segment cluster AA161187_node_24 of the present invention is supported by 12 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: AA161187_T16 and AA161187_T20. Table 445 below describes the start and end positions of this segment on each transcript.

Mutated protein alignment against previously known proteins:
Sequence name: TEST_HUMAN

Sequence documentation:

Alignment of: AA161187_P6 x TEST_HUMAN ..

Alignment segment 1/1:

Quality: 2894.00 Escore: 0
Matching length: 284 Total length: 284
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
43 GPCGRRVITSRIVGGEDAEL GRWPWQGSLRLWDSHVCGVSLLSHRWALTA 92
||||||||||||||||||||||||||||||||||||||||
31 GPCGRRVITSRIVGGEDAELGRWPWQGSLRLWDSHVCGVSLLSHRWALTA 80
....
93 AHCFETYSDLSDPSGWMVQFGQLTSMPSFWSLQAYYTRYFVSNIYLSPRY 142
||||||||||||||||||||||||||||||||||||||||
81 AHCFETYSDLDPPSGWMVQFGQLTSMPSFWSLQAYYTRYFVSNIYLSPRY 130
....
143 LGNSPYDIALVKLSAPVTYTKHIQPICLQASTFEFENRTDWVTGWGYIK 192
||||||||||||||||||||||||||||||||||||||||
131 LGNSPYDIALVKLSAPVTYTKHIQPICLQASTFEFENRTDCWVTGWGYIK 180
....
193 EDEALPSPHTLQEVQVAIINNSMCNHLFLKYSFRKDIGFDMVCAGNAQGG 242
||||||||||||||||||||||||||||||||||||||||
181 EDEALPSPHTLQEVQVAIINNSMCNHLFLKYSFRKDIGFDMVCAGNAQGG 230
....
243 KDACFGDSGGPLACNKNGLWYQIGVVSWGVGCGRPNRPGVYTNISHHFEW 292
||||||||||||||||||||||||||||||||||||||||
231 KDACFGDSGGPLACNKNGLWYQIGVVSWGVGCGRPNRPGVYTNISHHFEW 280
....
293 IQKLMAQSGMSQPDPPSWPLLFFPLLWALPLLGPV 326
|||||||||||||||||||||||||||||||
281 IQKLMAQSGMSQPDPPSWPLLFFPLLWALPLLGPV 314






Sequence name: TEST_HUMAN

Sequence documentation:

Alignment of: AA161187_P13 x TEST_HUMAN ..

Alignment segment 1/1:

Quality: 1829.00 Escore: 0
Matching length: 183 Total length: 183
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MGARGALLLLALLLARAGLRKPESQ EAAPLSGPCGRVTORSIVGGEDAEL 50
||||||||||||||||||||||||||||||||||||||||
1 MGARGALLLLALLLARAGLRKPESQ EAAPLSGPCGRVTORSIVGGEDAEL 50
....
51 GRWPWQGSLRLWDSHVCGVSLLSHRWALTAAHCFETYSDLDSPSGWMVQF 100
||||||||||||||||||||||||||||||||||||||||
51 GRWPWQGSLRLWDSHVCGVSLLSHRWALTAAHCFETYSDLDSPSGWMVQF 100
....
101 GQLTSMPSFWSLQAYY TRYFVSNIYLSPRYLGNSPYDIALVKLSAPVTYT 150
||||||||||||||||||||||||||||||||||||||||
101 GQLTSMPSFWSLQAYY TRYFVSNIYLSPRYLGNSPYDIALVKLSAPVTYT 150
....
151 KHIQPICLQASTFEFENRTDCW VTGWGYIKEDE 183
||||||||||||||||||||||||||||||
151 KHIQPICLQASTFEFENRTDCW VTGWGYIKEDE 183






Sequence name: TEST_HUMAN

Sequence documentation:

Alignment of: AA161187_P14 x TEST_HUMAN ..

Alignment segment 1/1:

Quality: 1829.00 Escore: 0
Matching length: 183 Total length: 183
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MGARGALLLLALLLARAGLRKPESQ EAAPLSGPCGRVTORSIVGGEDAEL 50
||||||||||||||||||||||||||||||||||||||||
1 MGARGALLLLALLLARAGLRKPESQ EAAPLSGPCGRVTORSIVGGEDAEL 50
....
51 GRWPWQGSLRLWDSHVCGVSLLSHRWALTAAHCFETYSDLDSPSGWMVQF 100
||||||||||||||||||||||||||||||||||||||||
51 GRWPWQGSLRLWDSHVCGVSLLSHRWALTAAHCFETYSDLDSPSGWMVQF 100
....
101 GQLTSMPSFWSLQAYY TRYFVSNIYLSPRYLGNSPYDIALVKLSAPVTYT 150
||||||||||||||||||||||||||||||||||||||||
101 GQLTSMPSFWSLQAYY TRYFVSNIYLSPRYLGNSPYDIALVKLSAPVTYT 150
....
151 KHIQPICLQASTFEFENRTDCW VTGWGYIKEDE 183
||||||||||||||||||||||||||||||
151 KHIQPICLQASTFEFENRTDCW VTGWGYIKEDE 183






Sequence name: TEST_HUMAN

Sequence documentation:

Alignment of: AA161187_P18 x TEST_HUMAN ..

Alignment segment 1/1:

Quality: 1957.00 Escore: 0
Matching length: 203 Total length: 205
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 99.02 Total Percent Identity: 99.02
Gaps: 1

Alignment:
....
43 GPCGRRVITSRIVGGEDAEL GRWPWQGSLRLWDSHVCGVSLLSHRWALTA 92
||||||||||||||||||||||||||||||||||||||||
31 GPCGRRVITSRIVGGEDAELGRWPWQGSLRLWDSHVCGVSLLSHRWALTA 80
....
93 AHCFET .. DLSDPSGWMVQFGQLTSMPSFWSLQAYYTRYFVSNIYLSPRY 140
|||||||||||||||||||||||||||||||||||||||
81 AHCFETYSDLDPPSGWMVQFGQLTSMPSFWSLQAYYTRYFVSNIYLSPRY 130
....
141 LGNSPYDIALVKLSAPVTYTKHIQPICLQASTFEFENRTDCWVTGWGYIK 190
||||||||||||||||||||||||||||||||||||||||
131 LGNSPYDIALVKLSAPVTYTKHIQPICLQASTFEFENRTDCWVTGWGYIK 180
....
191 EDEALPSPHTLQEVQVAIINNSMCNHLFLKYSFRKDIGFDMVCAGNAQGG 240
||||||||||||||||||||||||||||||||||||||||
181 EDEALPSPHTLQEVQVAIINNSMCNHLFLKYSFRKDIGFDMVCAGNAQGG 230

241 KDACF 245
||||||
231 KDACF 235






Sequence name: TEST_HUMAN

Sequence documentation:

Alignment of: AA161187_P19 x TEST_HUMAN ..

Alignment segment 1/1:

Quality: 1829.00 Escore: 0
Matching length: 183 Total length: 183
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MGARGALLLLALLLARAGLRKPESQ EAAPLSGPCGRVTORSIVGGEDAEL 50
||||||||||||||||||||||||||||||||||||||||
1 MGARGALLLLALLLARAGLRKPESQ EAAPLSGPCGRVTORSIVGGEDAEL 50
....
51 GRWPWQGSLRLWDSHVCGVSLLSHRWALTAAHCFETYSDLDSPSGWMVQF 100
||||||||||||||||||||||||||||||||||||||||
51 GRWPWQGSLRLWDSHVCGVSLLSHRWALTAAHCFETYSDLDSPSGWMVQF 100
....
101 GQLTSMPSFWSLQAYY TRYFVSNIYLSPRYLGNSPYDIALVKLSAPVTYT 150
||||||||||||||||||||||||||||||||||||||||
101 GQLTSMPSFWSLQAYY TRYFVSNIYLSPRYLGNSPYDIALVKLSAPVTYT 150
....
151 KHIQPICLQASTFEFENRTDCW VTGWGYIKEDE 183
||||||||||||||||||||||||||||||
151 KHIQPICLQASTFEFENRTDCW VTGWGYIKEDE 183

Expression of homo-sapiens protease, serine, 21 (testicin) (PRSS21) AA161187 transcript detectable by an amplicon shown in sequence name AA161187 seg 25 in normal and cancerous lung tissue seg25, AA 161 187 seg 25 amplicon (SEQ ID NO: 1654), and The expression of the homo-sapiens protease, serine, 21 (testicin) (PRSS21) AA161187 transcripts detectable by primers AA161187 seg17 F2 (SEQ ID NO: 1652) and AA161187 seg 17 R2 (SEQ ID NO: 1653) was measured by real time PCR. In parallel, four housekeeping genes-PBGD (GenBank Accession No. BC019323, Amplicon – PBGD-Amplicon, SEQ ID No. 334), HPRT1 (GenBank Accession No. NM_000194, Amplicon – HPRT1- Amplicons, SEQ ID NO: 1297), Ubiquitin (GenBank Accession No. BC000449, Amplicon – Ubiquitin-Amplicon SEQ ID NO: 328), and SDHA (GenBank Accession No. NM_004168, Amplicon – SDHA-Amplicon SEQ ID NO: 331) was similarly measured. For each RT sample, the expression of the amplicon was normalized to the geometric mean of the housekeeping gene dose. Normalized PM samples by dividing the normalized volume of each RT sample by the median volume of normal postmortem (PM) samples (sample numbers 47-50, 90-93, 96-99, Table 2 above) Magnifications of upregulation of each sample to the median of were obtained.

  FIG. 64 is a histogram showing over expression of the homo-Sapiens protease, serine, 21 (testicin) (PRSS21) transcripts in several cancerous lung samples compared to normal samples.

  As evident from FIG. 64, the expression of the homo-Sapiens protease, Serine, 21 (Testicin) (PRSS21) transcript, detectable by the above amplicon in several cancer samples, is a non-cancerous sample (Sample No. 46). 50, 90-93, 96-99, Table 2) significantly higher. Apparently, at least 6-fold overexpression was found in 1 out of 15 adenocarcinoma samples and 3 out of 16 squamous cell carcinoma samples and 1 out of 4 large cell carcinoma samples. The

  Primer pairs are also optionally and preferably included within the scope of the present invention, for example, in the above experiments the following primers were used only as non-limiting examples of suitable primer pairs: AA161187seg17F2 forward primer and AA161187seg17R2 reverse Direction primer.

  The present invention also preferably includes any amplicon obtained by use of any suitable primer pair (e.g. in the above experiments) and obtained the following amplicons only as a non-limiting illustration of a suitable amplicon : AA 161 187 seg 25.

Primer:
Forward primer AA161187seg17F2 (SEQ ID NO: 1652): CCCTGTGCCTTATTTGACCCT
Reverse primer AA161187seg17R2 (SEQ ID NO: 1653): GCTGGGTAGACTGGGTGCA
Amplicon AA 161 187 seg 25 (SEQ ID NO: 1654): CCTGTGCCTTATTTGACCCTCATGCCAACCCCGGGAGGGTGAGTG ACTGCTGACTCCAGCTAGCAAGAACGGAGGCTTGGCTGCTGCAGGGGGAGGA

Description of Cluster R66178 Cluster R66178 features 3 transcripts of interest and 16 segments, the names of which are shown in Tables 446 and 447 respectively, and the sequence itself is shown at the end of the application. Selected protein variants are shown in Table 448.

  These sequences are known proteins poliovirus receptor-related protein 1 precursor (SwissProt accession identifier PVR1_HUMAN), which is a known protein previously known in the present specification, synonym Herpes virus entry mediator C, HveC, Nectin 1. A variant of the herpes virus Ig-like receptor, also known as HIgR, CD111 antigen) (SEQ ID NO: 1432).

  The protein poliovirus receptor-related protein 1 precursor is known or considered to have the following functions: Alpha-herpesvirus (HSV-1 to cell, possibly involved in cell adhesion) HSV-2, and pseudorabies virus) receptors for invasion. The sequence of the protein poliovirus receptor related protein 1 precursor is shown at the end of the application as "poliovirus receptor related protein 1 precursor amino acid sequence". The localization of the protein poliovirus receptor-related protein 1 precursor is considered to be type I membrane proteins (isoforms α and δ) and secretion (isoform γ).

  The following GO annotation applies to previously known proteins. The following annotations were found: immune responses that are related to biological processes, cell-cell adhesion, cell adhesion receptors that are related to molecular function, protein binding, co-receptors, Adhesive junctions, integral membrane proteins that are annotations related to cellular components.

  GO assignments can be made at one or more http: // www. expasy. SwissProt / TremBl Protein knowledgebase available from ch / sprot / or http: // www. ncbi. nlm. nih. Depends on Locuslink available from gov / projects / LocusLink /.

  As mentioned above, cluster R66178 is characterized by the three transcripts listed in Table 1 above. These transcripts encode proteins which are variants of the protein poliovirus receptor related protein 1 precursor. A description of each mutein of the invention is provided herein.

  The mutein R66178_P3 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript R66178_T2. An alignment to a known protein (poliovirus receptor related protein 1 precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report on comparison between R66178_P3 and PVR1_HUMAN Corresponding to amino acids 1 to 334 of PVR1_HUMAN, corresponding to amino acids 1 to 334 of R66178_P3 MARMGLAGAAGRWWGLALGLTAFFLPGVHSQVVQVNDSMYGFIGTDVVLHCSFANPLPSVKITQVTWQKSTNGSKQNVAIYNPSMGVSVLAPYRERVEFLRPSFTDGTIRLSRLELEDEGVYICEFATFPTGNRESQLNLTVMAKPTNWIEGTQAVLRAKKGQDDKVLVATCTSANGKPPSVVSWETRLKGEAEYQEIRNPNGTVTVISRYRLVPSREAHQQSLACIVNYHMDRFKESLTLNVQYEPEVTIEGFDGNWYLQRMDVKLTCKADANPPATEYHWT At least 70%, optionally at least 80%, preferably at least 85%, with a polypeptide having the sequence GEGHSLPISPGGVLQTQNCGP corresponding to the first amino acid sequence at least 90% homologous to LNGSLPKGVEAQNRTLFFKGPINYAGAGTYTYEATNAGIGTGSGVEVNIT and amino acids 335-354 of R66178_P3 Comprises a second amino acid sequence which is at least 90%, most preferably at least 95% homologous, the first amino acid sequence and the second amino acid sequence encoding R66178_P3, adjacent and in sequential order Isolated chimeric polypeptide.

  2. R66178_P3 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence GEGHSLPISPVGVLQTQNCGP in R66178_P3 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein R66178_P3 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing the other amino acids, and listing the other amino acids, as shown in Table 449) It is shown whether it is known and the presence of a known SNP in the mutant protein R66178_P3 sequence supports the deduced sequence of this mutant protein of the invention).

  The glycosylation sites of the mutant protein R66178_P3 compared to the known protein poliovirus receptor related protein 1 precursor are shown in Table 450 (showing its position on the amino acid sequence in the first column, the second column Indicates whether the site of transformation is present in the mutein and the last column indicates whether this position is different on the mutein).

  The mutein R66178_P3 is encoded by the following transcript: R66178_T2 (sequences shown at the end of the application). The coding part of the transcript R66178_T2 is shown in bold, starting from position 634 and ending at position 1695. The transcript also has the following SNPs listed in Table 451 (showing its position on the nucleotide sequence and listing another nucleic acid, the last column indicating whether the SNP is known, mutein R66178_P3 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein R66178_P4 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript R66178_T3. An alignment to a known protein (poliovirus receptor related protein 1 precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between R66178_P4 and PVR1_HUMAN Corresponding to amino acids 1 to 334 of PVR1_HUMAN, corresponding to amino acids 1 to 334 of R66178_P4 MARMGLAGAAGRWWGLALGLTAFFLPGVHSQVVQVNDSMYGFIGTDVVLHCSFANPLPSVKITQVTWQKSTNGSKQNVAIYNPSMGVSVLAPYRERVEFLRPSFTDGTIRLSRLELEDEGVYICEFATFPTGNRESQLNLTVMAKPTNWIEGTQAVLRAKKGQDDKVLVATCTSANGKPPSVVSWETRLKGEAEYQEIRNPNGTVTVISRYRLVPSREAHQQSLACIVNYHMDRFKESLTLNVQYEPEVTIEGFDGNWYLQRMDVKLTCKADANPPATEYHWT At least 70%, optionally at least 80%, preferably at least 85%, with a polypeptide having the first amino acid sequence at least 90% homologous to LNGSLPKGVEAQNRTLFFKGPINYAGAGTYTYEATATIG PIGTRSGQ VEVNIT and the sequence AFCQLIYPGKGRTRARMMF corresponding to amino acids 335-352 of R66178_P4 Comprises a second amino acid sequence that is at least 90%, most preferably at least 95% homologous, the first amino acid sequence and the second amino acid sequence encoding R66178_P4, adjacent and in sequential order Isolated chimeric polypeptide.

  2. R66178_P4 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence AFCQLIYPGKGRTRARMF in R66178_P4 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein R66178_P4 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing the other amino acids, and listing the other amino acids, as shown in Table 452, the last It is shown whether it is known and the presence of known SNPs in the mutein R66178_P4 sequence supports the deduced sequence of this mutein of the invention).

  The glycosylation sites of the mutant protein R66178_P4 compared to the known protein poliovirus receptor related protein 1 precursor are shown in Table 453 (showing its position on the amino acid sequence in the first column, the second column Indicates whether the site of transformation is present in the mutein and the last column indicates whether this position is different on the mutein).

  The mutein R66178_P4 is encoded by the following transcript: R66178_T3 (sequences shown at the end of the application). The coding part of the transcript R66178_T3 is shown in bold, starting from position 634 and ending at position 1689. The transcript also has the following SNPs listed in Table 454 (showing its position on the nucleotide sequence and listing another nucleic acid, the last column shows whether the SNP is known, mutein R66178_P4 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

The mutein R66178_P8 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript R66178_T7. An alignment to a known protein (poliovirus receptor related protein 1 precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report on comparison between R66178_P8 and PVR1_HUMAN Corresponding to amino acids 1 to 330 of PVR1_HUMAN, corresponding to amino acids 1 to 330 of R66178_P8 MARMGLAGAAGRWWGLALGLTAFFLPGVHSQVVQVNDSMYGFIGTDVVLHCSFANPLPSVKITQVTWQKSTNGSKQNVAIYNPSMGVSVLAPYRERVEFLRPSFTDGTIRLSRLELEDEGVYICEFATFPTGNRESQLNLTVMAKPTNWIEGTQAVLRAKKGQDDKVLVATCTSANGKPPSVVSWETRLKGEAEYQEIRNPNGTVTVISRYRLVPSREAHQQSLACIVNYHMDRFKESLTLNVQYEPEVTIEGFDGNWYLQRMDVKLTCKADANPPATEYHWT At least 70%, preferably at least 80%, preferably at least 85%, more preferably a first amino acid sequence which is at least 90% homologous to LNGSLPKGVEAQNRTLFFKGPINYSLAGICTYNPIGTRSGQVE and a sequence NSPTPRLLPNMGGAPGRCPRPSLGAWRGASCWC corresponding to amino acids 331 to 363 of R66178_P8, preferably at least 85%, preferably at least 85% Comprises R66178_P8, comprising a second amino acid sequence which is at least 90%, most preferably at least 95% homologous, said first amino acid sequence and the second amino acid sequence being adjacent and in a consecutive order Isolated chimeric polypeptide.

  2. R66178_P8 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence NSPTPRLLPNMGGAPGRCPRPSLGAWRGASCWC in R66178_P8 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein R66178_P8 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing the other amino acids, and listing the other amino acids, as shown in Table 455), and the last column is the SNP It is shown whether it is known and the presence of a known SNP in the mutein R66178_P8 sequence supports the deduced sequence of this mutein of the invention).

  The glycosylation sites of the mutant protein R66178_P8 compared to the known protein poliovirus receptor related protein 1 precursor are shown in Table 456 (showing its position on the amino acid sequence in the first column, the second column Indicates whether the site of transformation is present in the mutein and the last column indicates whether this position is different on the mutein).

  The mutein R66178_P8 is encoded by the following transcript: R66178_T7 (sequences shown at the end of the application). The coding part of the transcript R66178_T7 is shown in bold, starting from position 634 and ending at position 1722. The transcript also has the following SNPs listed in Table 457 (indicating its position on the nucleotide sequence and listing another nucleic acid, the last column indicating whether the SNP is known, mutein R66178_P8 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  As mentioned above, cluster R66178 is characterized by the sixteen segments listed in Table 2 above, the sequence of which is shown at the end of the application. These segments are part of the nucleic acid sequence, which are of particular interest and are individually described herein. A description of each segment of the invention is provided herein.

  The segment cluster R66178_node_0 of the present invention is supported by 19 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R66178_T2, R66178_T3, and R66178_T7. Table 458 below describes the start and end positions of this segment on each transcript.

  The segment cluster R66178_node_6 of the present invention is supported by 39 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R66178_T2, R66178_T3, and R66178_T7. Table 459 below describes the start and end positions of this segment on each transcript.

  The segment cluster R66178_node_8 of the present invention is supported by 39 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R66178_T2, R66178_T3, and R66178_T7. Table 460 below describes the start and end positions of this segment on each transcript.

  Microarray (chip) data for this segment is also available, as follows. As described above, with respect to the clusters themselves, different oligonucleotides were tested for differential expression in different disease states, in particular cancer. The following oligonucleotides were found to reach this segment (for lung cancer) (shown in Table 461).

  The segment cluster R66178_node_15 of the present invention is supported by 40 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R66178_T2, R66178_T3, and R66178_T7. Table 462 below describes the start and end positions of this segment on each transcript.

  The segment cluster R66178_node_24 of the present invention is supported by 10 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R66178_T2. Table 463 below describes the start and end positions of this segment on each transcript.

  The segment cluster R66178_node_26 of the present invention is supported by 24 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R66178_T7. Table 464 below describes the start and end positions of this segment on each transcript.

  The segment cluster R66178_node_27 of the present invention is supported by 12 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R66178_T7. Table 465 below describes the start and end positions of this segment on each transcript.

  According to an optional embodiment of the present invention, there is also provided a short segment associated with the above cluster. These segments are up to about 120 bp in length and are therefore included in the individual descriptions.

  The segment cluster R66178_node_4 of the present invention is supported by 21 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R66178_T2, R66178_T3, and R66178_T7. Table 466 below describes the start and end positions of this segment on each transcript.

  The segment cluster R66178_node_5 of the invention can be found in the following transcripts: R66178_T2, R66178_T3, and R66178_T7. Table 467 below describes the start and end positions of this segment on each transcript.

  The segment cluster R66178_node_9 of the present invention is supported by 44 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R66178_T2, R66178_T3, and R66178_T7. Table 468 below describes the start and end positions of this segment on each transcript.

  The segment cluster R66178_node_11 of the present invention is supported by 44 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R66178_T2, R66178_T3, and R66178_T7. Table 469 below describes the start and end positions of this segment on each transcript.

  The segment cluster R66178_node_16 of the invention can be found in the following transcripts: R66178_T2 and R66178_T3. Table 470 below describes the start and end positions of this segment on each transcript.

  The segment cluster R66178_node_18 of the present invention is supported by 13 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R66178_T3. Table 471 below describes the start and end positions of this segment on each transcript.

  The segment cluster R66178_node_19 according to the invention can be found in the following transcript: R66178_T3. Table 472 below describes the start and end positions of this segment on each transcript.

  The segment cluster R66178_node_20 of the present invention is supported by 12 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R66178_T3. Table 473 below describes the start and end positions of this segment on each transcript.

  The segment cluster R66178_node_21 of the present invention is supported by 11 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R66178_T3. Table 474 below describes the start and end positions of this segment on each transcript.

Mutated protein alignment against previously known proteins:
Sequence name: PVR1_HUMAN

Sequence documentation:

Alignment of: R66178_P3 x PVR1_HUMAN ..

Alignment segment 1/1:

Quality: 3286.00 Escore: 0
Matching length: 334 Total length: 334
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MARMGLAGA AGRWWGLALGLTAFFLPGVHSQVVQVNDSMYGFIGTDVVLH 50
||||||||||||||||||||||||||||||||||||||||
1 MARMGLAGA AGRWWGLALGLTAFFLPGVHSQVVQVNDSMYGFIGTDVVLH 50
....
51 CSFANPLPSVKITQVTWQKSTNGSK QNVAIYNPSMGVSLAPYRERVEFL 100
||||||||||||||||||||||||||||||||||||||||
51 CSFANPLPSVKITQVTWQKSTNGSK QNVAIYNPSMGVSLAPYRERVEFL 100
....
101 RPSFTDGTIRLSRLELEDEGVYICEFATFPTGNRESQLNLTVMAKPTNWI 150
||||||||||||||||||||||||||||||||||||||||
101 RPSFTDGTIRLSRLELEDEGVYICEFATFPTGNRESQLNLTVMAKPTNWI 150
....
151 EGTQAVLRAKKGQDDKVLVATCTSANGKPPSV VSWETRLKGEAEYQEIRN 200
||||||||||||||||||||||||||||||||||||||||
151 EGTQAVLRAKKGQDDKVLVATCTSANGKPPSV VSWETRLKGEAEYQEIRN 200
....
201 PNGTVTVISRYRLVPSREAHQQSLACIVNYHMDRFKESLTLNVQYEPEVT 250
||||||||||||||||||||||||||||||||||||||||
201 PNGTVTVISRYRLVPSREAHQQSLACIVNYHMDRFKESLTLNVQYEPEVT 250
....
251 IEGFDGNWYLQRMDV KLTCKADANPPATEEHWTTLNGSLPKGVEAQNRTL 300
||||||||||||||||||||||||||||||||||||||||
251 IEGFDGNWYLQRMDV KLTCKADANPPATEEHWTTLNGSLPKGVEAQNRTL 300
....
301 FFKPINYSLAGTYCEATNPIGTRSGQVEVNIT 334
|||||||||||||||||||||||||||||||
301 FFKPINYSLAGTYCEATNPIGTRSGQVEVNIT 334






Sequence name: PVR1_HUMAN

Sequence documentation:

Alignment of: R66178_P4 x PVR1_HUMAN ..

Alignment segment 1/1:

Quality: 3294.00 Escore: 0
Matching length: 336 Total length: 336
Matching Percent Similarity: 99.70 Matching Percent Identity: 99.70
Total Percent Similarity: 99.70 Total Percent Identity: 99.70
Gaps: 0

Alignment:
....
1 MARMGLAGA AGRWWGLALGLTAFFLPGVHSQVVQVNDSMYGFIGTDVVLH 50
||||||||||||||||||||||||||||||||||||||||
1 MARMGLAGA AGRWWGLALGLTAFFLPGVHSQVVQVNDSMYGFIGTDVVLH 50
....
51 CSFANPLPSVKITQVTWQKSTNGSK QNVAIYNPSMGVSLAPYRERVEFL 100
||||||||||||||||||||||||||||||||||||||||
51 CSFANPLPSVKITQVTWQKSTNGSK QNVAIYNPSMGVSLAPYRERVEFL 100
....
101 RPSFTDGTIRLSRLELEDEGVYICEFATFPTGNRESQLNLTVMAKPTNWI 150
||||||||||||||||||||||||||||||||||||||||
101 RPSFTDGTIRLSRLELEDEGVYICEFATFPTGNRESQLNLTVMAKPTNWI 150
....
151 EGTQAVLRAKKGQDDKVLVATCTSANGKPPSV VSWETRLKGEAEYQEIRN 200
||||||||||||||||||||||||||||||||||||||||
151 EGTQAVLRAKKGQDDKVLVATCTSANGKPPSV VSWETRLKGEAEYQEIRN 200
....
201 PNGTVTVISRYRLVPSREAHQQSLACIVNYHMDRFKESLTLNVQYEPEVT 250
||||||||||||||||||||||||||||||||||||||||
201 PNGTVTVISRYRLVPSREAHQQSLACIVNYHMDRFKESLTLNVQYEPEVT 250
....
251 IEGFDGNWYLQRMDV KLTCKADANPPATEEHWTTLNGSLPKGVEAQNRTL 300
||||||||||||||||||||||||||||||||||||||||
251 IEGFDGNWYLQRMDV KLTCKADANPPATEEHWTTLNGSLPKGVEAQNRTL 300
....
301 FFKPINYSLAGTYCEATNPIGTRSGQVEVNITAF 336
||||||||||||||||||||||||||||||
301 FFKPINYSLAGTYCEATNPIGTRSGQVEVNITEF 336






Sequence name: PVR1_HUMAN

Sequence documentation:

Alignment of: R66178_P8 x PVR1_HUMAN ..

Alignment segment 1/1:

Quality: 3250.00 Escore: 0
Matching length: 330 Total length: 330
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MARMGLAGA AGRWWGLALGLTAFFLPGVHSQVVQVNDSMYGFIGTDVVLH 50
||||||||||||||||||||||||||||||||||||||||
1 MARMGLAGA AGRWWGLALGLTAFFLPGVHSQVVQVNDSMYGFIGTDVVLH 50
....
51 CSFANPLPSVKITQVTWQKSTNGSK QNVAIYNPSMGVSLAPYRERVEFL 100
||||||||||||||||||||||||||||||||||||||||
51 CSFANPLPSVKITQVTWQKSTNGSK QNVAIYNPSMGVSLAPYRERVEFL 100
....
101 RPSFTDGTIRLSRLELEDEGVYICEFATFPTGNRESQLNLTVMAKPTNWI 150
||||||||||||||||||||||||||||||||||||||||
101 RPSFTDGTIRLSRLELEDEGVYICEFATFPTGNRESQLNLTVMAKPTNWI 150
....
151 EGTQAVLRAKKGQDDKVLVATCTSANGKPPSV VSWETRLKGEAEYQEIRN 200
||||||||||||||||||||||||||||||||||||||||
151 EGTQAVLRAKKGQDDKVLVATCTSANGKPPSV VSWETRLKGEAEYQEIRN 200
....
201 PNGTVTVISRYRLVPSREAHQQSLACIVNYHMDRFKESLTLNVQYEPEVT 250
||||||||||||||||||||||||||||||||||||||||
201 PNGTVTVISRYRLVPSREAHQQSLACIVNYHMDRFKESLTLNVQYEPEVT 250
....
251 IEGFDGNWYLQRMDV KLTCKADANPPATEEHWTTLNGSLPKGVEAQNRTL 300
||||||||||||||||||||||||||||||||||||||||
251 IEGFDGNWYLQRMDV KLTCKADANPPATEEHWTTLNGSLPKGVEAQNRTL 300
....
301 FFKPINYSLAGTYCEATNPIGTRSGQVE 330
||||||||||||||||||||||||||||
301 FFKPINYSLAGTYCEATNPIGTRSGQVE 330

Description of cluster HUMPHOSLIP The cluster HUMPHOSLIP is characterized by 7 transcripts and 53 segments of interest, the names of which are shown in Tables 475 and 476 respectively and the sequence itself is shown at the end of the application. Selected protein variants are shown in Table 477.

  These sequences are phospholipid transfer protein precursors (SwissProt accession identifier PLTP_HUMAN, also known as synonym lipid transfer protein II), which is a known protein, which is referred to herein as a protein previously known as SEQ ID NO: 1433).

  Protein Phospholipid Transfer Protein Precursors are known or are considered to have the following functions: Convert HDL into larger and smaller particles. It may play an important role in extracellular phospholipid transport and modulation of HDL particles. The sequence of the protein phospholipid transfer protein precursor is shown at the end of the application as "phospholipid transfer protein precursor amino acid sequence". Known polymorphisms of this sequence are shown in Table 478.

  Localization of the protein phospholipid transport protein precursor is considered secretion.

  The following GO annotation applies to previously known proteins. The following annotations were found: lipid metabolism, lipid transport, annotation related to biological processes, lipid binding, annotation related to molecular function, extracellular, annotation related to cellular components .

  GO assignments can be made at one or more http: // www. expasy. SwissProt / TremBl Protein knowledgebase available from ch / sprot / or http: // www. ncbi. nlm. nih. Depends on Locuslink available from gov / projects / LocusLink /.

  For this cluster, at least one oligonucleotide was found to demonstrate overexpression of the cluster, but not in at least one transcript / segment listed below. Microarray (chip) data for this segment is also available, as follows. As noted above, different oligonucleotides were tested for differential expression in different disease states, in particular cancer. The following oligonucleotides were found to reach this segment for lung cancer but not the other segments / transcripts below (shown in Table 479).

  As mentioned above, the cluster HUMPHOSLIP is characterized by the seven transcripts listed in Table 1 above. These transcripts encode proteins which are variants of the protein phospholipid transport protein precursor. A description of each mutein of the invention is provided herein.

  The mutein HUMPHOSLIP_PEA_2_P10 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript HUMPHOSLIP_PEA_2_T17. An alignment to known proteins (phospholipid transfer protein precursors) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between HUMPHOSLIP_PEA_2_P10 and PLTP_HUMAN 1. MALGFAL FLALLAGA EEF PG CCK IR VTS KALELE V KQ EGL L FLE EQ ELET I IT L P L DIG RG G E G F YNISE corresponding to amino acids 1 to 67 of PLTP_HUMAN and corresponding to amino acids 1 to 67 of HUMPHOSLIP_PEA_2_P10 Also corresponds to KVYDFLSTFITSGMRFLNQQICPVLYHAGTPVLLSLLDTVPVRSSVDELDESYLMKPDVASTSLDMDFRGAFFPLTERNWSLPNRAVEPQLQEEERMVYVAFSEFFDSAMESYFR GALQLLLVGDKVPHDLDMLLRATYFGSIVLLSPAVIDSPLKLELRVLAPPRCTIKPSGTTISVTASVTIALVPPDQPEVQLSSMTMDARLSAKMALRGKALRTQLDLRRFRIYSNHSALESLALIPLQAPLKTMLQIGVMPMLNERTWRGVQIPLPEGINFVHEVVTNHAGFLTIGADLHFAKGLREVIEKNRPADVRASTAPTPSTAAV and and at least 90% homologous to a second amino acid sequence, the first amino acid sequence and a second amino acid sequence, contiguous and in sequential order, the isolated chimeric polypeptide encoding HUMPHOSLIP_PEA_2_P10 .

  2. Length “n” (wherein n is at least about 10 amino acids long, optionally at least about 20 amino acids long, preferably at least about 30 amino acids long, more preferably at least about 40 amino acids long, most preferably at least about 50 amino acids in length, at least two amino acids comprising EK, starting from any of the following structures: amino acid numbers 67-x to 67, amino acid numbers 68 + ((n-2) -x) (formula An isolated chimeric polypeptide encoding the edge portion of HUMPHOSLIP_PEA_2_P10, comprising a polypeptide, having a sequence terminating in:), with a sequence terminating at 0 to n-2).

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein HUMPHOSLIP_PEA_2_P10 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows the SNPs as shown in Table 480) It indicates whether it is known and the presence of a known SNP in the mutant protein HUMPHOSLIP_PEA_2_P10 sequence supports the deduced sequence of this mutant protein according to the invention).

  The glycosylation sites of the mutant protein HUMPHOSLIP_PEA_2_P10 compared to known protein phospholipid transfer protein precursors are shown in Table 481 (showing its position on the amino acid sequence in the first column, the second column has a glycosylation site It indicates whether it is present in the mutein and the last column shows whether this position is different on the mutein).

  The mutein HUMPHOSLIP_PEA_2_P10 is encoded by the following transcript: HUMPHOSLIP_PEA_2_T17 (sequences shown at the end of the application). The code portion of the transcript HUMPHOSLIP_PEA_2_T17 is shown in bold, starting from position 276 and ending at position 1469. The transcript also has the following SNPs listed in Table 482 (showing its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, the mutein HUMPHOSLIP_PEA_2_P10 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein HUMPHOSLIP_PEA_2_P12 according to the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript HUMPHOSLIP_PEA_2_T19. An alignment to known proteins (phospholipid transfer protein precursors) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between HUMPHOSLIP_PEA_2_P12 and PLTP_HUMAN 1. Corresponding to amino acids 1 to 427 of PLTP_HUMAN, corresponding to amino acids 1 to 427 of HUMPHOSLIP_PEA_2_P12 MALFGALFLALLAGAHAEFPGCKIRVTSKALELVKQEGLRFLEQELETITIPDLRGKEGHFYYNISEVKVTELQLTSSELDFQPQQELMLQITNASLGLRFRRQLLYWFFYDGGYINASAEGVSIRTGLELSRDPAGRMKVSNVSCQASVSRMHAAFGGTFKKVYDFLSTFITSGMRFLLNQQICPVLYHAGTVLLNSLLDTVPVRSSVDELVGIDYSLMKDPVASTSNLDMDFRGAFFPLTERNWSLPNRAVEPQLQEEERMVYVAFSEFF DSAMESYFRAGALQLLLVGDKVPHDLML LYFTYFLSIFLLSPA DSPSL KLELRAPPCTIKPSGTTISV TASVPIALVP PDQPEVQLSSMTMDARLSAKMALRG KALRT QL DRRI RISN HSL ASL SL PL Q PL M PL M is a 7-port metal sheet and a metal sheet Comprises a second amino acid sequence which is at least 90%, most preferably at least 95% homologous, said first amino acid sequence and 2 amino acid sequences, contiguous and in sequential order, the isolated chimeric polypeptide coding HUMPHOSLIP_PEA_2_P12.

  2. Of HUMPHOSLIP_PEA_2_P12 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence GKAGV in HUMPHOSLIP_PEA_2_P12 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein HUMPHOSLIP_PEA_2_P12 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, enumerating other amino acids, and the last column shows SNPs as shown in Table 483) It indicates whether it is known and the presence of a known SNP in the mutant protein HUMPHOSLIP_PEA_2_P12 sequence supports the deduced sequence of this mutant protein of the invention).

  The glycosylation sites of the mutant protein HUMPHOSLIP_PEA_2_P12 compared to known protein phospholipid transfer protein precursors are shown in Table 484 (showing its position on the amino acid sequence in the first column, the second column has glycosylation sites It indicates whether it is present in the mutein and the last column shows whether this position is different on the mutein).

  The mutein HUMPHOSLIP_PEA_2_P12 is encoded by the following transcript: HUMPHOSLIP_PEA_2_T19 (sequences shown at the end of the application). The code portion of the transcript HUMPHOSLIP_PEA_2_T19 is shown in bold, starting from position 276 and ending at position 1571. The transcript also has the following SNPs listed in Table 485 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, the mutein HUMPHOSLIP_PEA_2_P12 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein HUMPHOSLIP_PEA_2_P30 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript HUMPHOSLIP_PEA_2_T6. The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein HUMPHOSLIP_PEA_2_P30 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows the SNPs as shown in Table 486) It indicates whether it is known and the presence of a known SNP in the mutant protein HUMPHOSLIP_PEA_2_P30 sequence supports the predicted sequence of this mutant protein of the invention).

  The mutein HUMPHOSLIP_PEA_2_P30 is encoded by the following transcript: HUMPHOSLIP_PEA_2_T6 (sequences shown at the end of the application). The code portion of the transcript HUMPHOSLIP_PEA_2_T6 is shown in bold, starting from position 276 and ending at position 431. The transcript also has the following SNPs listed in Table 487 (indicating its position on the nucleotide sequence and listing another nucleic acid, the last column indicates whether the SNP is known, the mutein HUMPHOSLIP_PEA_2_P30 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein HUMPHOSLIP_PEA_2_P31 of the present invention has the amino acid sequence shown at the end of the application and is encoded by the transcript HUMPHOSLIP_PEA_2_T7. An alignment to known proteins (phospholipid transfer protein precursors) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between HUMPHOSLIP_PEA_2_P31 and PLTP_HUMAN 1. MALGFAL FLALLAGA EEF PG CCK IR VTS ALELE V KQ EGLR LLEQ ELET I TIP L G RG G E G YY HJ corresponding to amino acids 1 to 67 of PLTP_HUMAN and corresponding to amino acids 1 to 67 of HUMPHOSL_PEA_2_P 31 Said second amino acid sequence comprising a second amino acid sequence which is at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous; Ami of 2 Acid sequence, contiguous and in sequential order, the isolated chimeric polypeptide coding HUMPHOSLIP_PEA_2_P31.

  2. HUMPHOSLIP_PEA_2_P31 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 80%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence PGLERGADKFPVVGGSLSLALDLTLP PVG in An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein HUMPHOSLIP_PEA_2_P31 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, enumerating other amino acids, and the last column shows SNPs as shown in Table 488) It indicates whether it is known and the presence of a known SNP in the mutant protein HUMPHOSLIP_PEA_2_P31 sequence supports the deduced sequence of this mutant protein of the invention).

  The glycosylation sites of mutant protein HUMPHOSLIP_PEA_2_P31 compared to known protein phospholipid transfer protein precursors are shown in Table 489 (showing its position on the amino acid sequence in the first column, the second column has glycosylation sites It indicates whether it is present in the mutein and the last column shows whether this position is different on the mutein).

  The mutein HUMPHOSLIP_PEA_2_P31 is encoded by the following transcript: HUMPHOSLIP_PEA_2_T7 (sequences shown at the end of the application). The code portion of the transcript HUMPHOSLIP_PEA_2_T7 is shown in bold, starting from position 276 and ending at position 569. The transcript also has the following SNPs listed in Table 490 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, the mutein HUMPHOSLIP_PEA_2_P31 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein HUMPHOSLIP_PEA_2_P33 of the present invention has the amino acid sequence shown at the end of the application and is encoded by the transcript HUMPHOSLIP_PEA_2_T14. An alignment to known proteins (phospholipid transfer protein precursors) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between HUMPHOSLIP_PEA_2_P33 and PLTP_HUMAN 1. Corresponding to amino acids 1-183 of PLTP_HUMAN, the polypeptide having a MALFGALFLALLAGAHAEFPGCKIRVTSKALELVKQEGLRFLEQELETITIPDLRGKEGHFYYNISEVKVTELQLTSSELDFQPQQELMLQITNASLGLRFRRQLLYWFFYDGGYINASAEGVSIRTGLELSRDPAGRMKVSNVSCQASVSRMHAAFGGTFKKVYDFLSTFITSGMRFLLNQQ corresponding to amino acids 1-183 of HUMPHOSLIP_PEA_2_P33 the first amino acid sequence at least 90% homologous, sequences corresponding to VWAATGRRVARVGMLSL to amino acid 184-200 of HUMPHOSLIP_PEA_2_P33 Said second amino acid sequence comprising a second amino acid sequence which is at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous; An isolated chimeric polypeptide encoding HUMPHOSLIP_PEA_2_P33, wherein the two amino acid sequences are in contiguous and sequential order.

  2. HUMPHOSLIP_PEA_2_P33 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence VWAATGRRVARVGMLSL in HUMPHOSLIP_PEA_2_P33 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein HUMPHOSLIP_PEA_2_P33 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows the SNPs, as shown in Table 491) It indicates whether it is known and the presence of a known SNP in the mutant protein HUMPHOSLIP_PEA_2_P33 sequence supports the deduced sequence of this mutant protein according to the invention).

  The glycosylation sites of the mutant protein HUMPHOSLIP_PEA_2_P33 compared to known protein phospholipid transfer protein precursors are shown in Table 492 (showing its position on the amino acid sequence in the first column, the second column has glycosylation sites It indicates whether it is present in the mutein and the last column shows whether this position is different on the mutein).

  The mutein HUMPHOSLIP_PEA_2_P33 is encoded by the following transcript: HUMPHOSLIP_PEA_2_T14 (sequences shown at the end of the application). The code portion of the transcript HUMPHOSLIP_PEA_2_T14 is shown in bold, starting from position 276 and ending at position 875. The transcript also has the following SNPs listed in Table 493 (showing its position on the nucleotide sequence and listing another nucleic acid, the last column shows if the SNP is known, the mutein HUMPHOSLIP_PEA_2_P33 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein HUMPHOSLIP_PEA_2_P34 according to the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript HUMPHOSLIP_PEA_2_T16. An alignment to known proteins (phospholipid transfer protein precursors) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between HUMPHOSLIP_PEA_2_P34 and PLTP_HUMAN 1. Corresponding to amino acids 1-205 of PLTP_HUMAN, first amino acid sequence at least 90% homologous to the corresponding MALFGALFLALLAGAHAEFPGCKIRVTSKALELVKQEGLRFLEQELETITIPDLRGKEGHFYYNISEVKVTELQLTSSELDFQPQQELMLQITNASLGLRFRRQLLYWFFYDGGYINASAEGVSIRTGLELSRDPAGRMKVSNVSCQASVSRMHAAFGGTFKKVYDFLSTFITSGMRFLLNQQICPVLYHAGTVLLNSLLDTVPV to amino acids 1-205 of HUMPHOSLIP_PEA_2_P34, corresponding to amino acids 206-217 of HUMPHOSLIP_PEA_2_P34 sequence LWTSL A polypeptide having ALTIPS and a second amino acid sequence which is at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous; An isolated chimeric polypeptide encoding HUMPHOSLIP_PEA_2_P34, wherein the amino acid sequence of 1 and the second amino acid sequence are adjacent and in sequential order.

  2. HUMPHOSLIP_PEA_2_P34 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence LWTSLLALTIPS in HUMPHOSLIP_PEA_2_P34 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein HUMPHOSLIP_PEA_2_P34 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows the SNPs as shown in Table 494) It indicates whether it is known and the presence of a known SNP in the mutant protein HUMPHOSLIP_PEA_2_P34 sequence supports the deduced sequence of this mutant protein of the invention).

  The glycosylation sites of mutant protein HUMPHOSLIP_PEA_2_P34 compared to known protein phospholipid transfer protein precursors are shown in Table 495 (showing its position on the amino acid sequence in the first column, the second column has glycosylation sites It indicates whether it is present in the mutein and the last column shows whether this position is different on the mutein).

  The mutein HUMPHOSLIP_PEA_2_P34 is encoded by the following transcript: HUMPHOSLIP_PEA_2_T16 (sequences shown at the end of the application). The code portion of the transcript HUMPHOSLIP_PEA_2_T16 is shown in bold, starting from position 276 and ending at position 926. The transcript also has the following SNPs listed in Table 496 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, the mutein HUMPHOSLIP_PEA_2_P34 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein HUMPHOSLIP_PEA_2_P35 according to the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript HUMPHOSLIP_PEA_2_T18. An alignment to known proteins (phospholipid transfer protein precursors) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report on comparison between HUMPHOSLIP_PEA_2_P35 and PLTP_HUMAN 1. MALFFAL FLH meeting at least 90% of the amino acid sequence A third amino acid sequence which is at least 90% homologous to KVYDFLSTFITSGMFRNLQQ, which corresponds to amino acids 163 to 183 of and also to amino acids 111 to 131 of HUMPHOSLIP_PEA_2_P35, and HUMPH At least 70%, optionally at least 80%, preferably at least 85%, preferably at least 90%, more preferably at least 90%, most preferably at least 95% homologous to a polypeptide having the sequence VWAATGRRVARVGMLSL corresponding to amino acids 132 to 148 of SLIP_PEA_2_P35 A single HMPHOSLIP_PEA_2_P35 encoding comprising the four amino acid sequences, wherein said first amino acid sequence, second amino acid sequence, third amino acid sequence and fourth amino acid sequence are adjacent and in sequential order Detached chimeric polypeptide.

  2. Length “n” (wherein n is at least about 10 amino acids long, optionally at least about 20 amino acids long, preferably at least about 30 amino acids long, more preferably at least about 40 amino acids long, most preferably at least about Having the length of 50 amino acids, at least two amino acids comprising FLK and having the following structure (numbering corresponding to HUMPHOSLIP_PEA_2_P35): starting from any of amino acids 109-x to 109, amino acids 111+ ((n -2)-x) An isolated chimeric polypeptide encoding the edge portion of HUMPHOSLIP_PEA_2_P35, comprising a polypeptide, having a sequence terminating at: where x varies from 0 to n-2.

  3. HUMPHOSLIP_PEA_2_P35 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence VWAATGRRVARVGMLSL in HUMPHOSLIP_PEA_2_P35 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein HUMPHOSLIP_PEA_2_P35 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows the SNP as shown in Table 497) It indicates whether it is known and the presence of a known SNP in the mutant protein HUMPHOSLIP_PEA_2_P35 sequence supports the deduced sequence of this mutant protein of the invention).

  The glycosylation sites of the mutant protein HUMPHOSLIP_PEA_2_P35 compared to known protein phospholipid transfer protein precursors are shown in Table 498 (showing its position on the amino acid sequence in the first column, the second column has glycosylation sites It indicates whether it is present in the mutein and the last column shows whether this position is different on the mutein).

  The mutein HUMPHOSLIP_PEA_2_P35 is encoded by the following transcript: HUMPHOSLIP_PEA_2_T18 (sequences shown at the end of the application). The code portion of the transcript HUMPHOSLIP_PEA_2_T18 is shown in bold, starting from position 276 and ending at position 719. The transcript also has the following SNPs listed in Table 499 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, the mutein HUMPHOSLIP_PEA_2_P35 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  As mentioned above, the cluster HUMPHOSLIP is characterized by the 53 segments listed in Table 2 above, the sequence of which is shown at the end of the application. These segments are part of the nucleic acid sequence, which are of particular interest and are individually described herein. A description of each segment of the invention is provided herein.

  The segment cluster HUMPHOSLIP_PEA_2_node_0 of the present invention is supported by 150 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMPHOSLIP_PEA_2_T6, HUMPHOSLIP_PEA_2_T7, HUMPHOSLIP_PEA_2_T14, HUMPHOSLIP_PEA_2_T16, HUMPHOSLIP_PEA_2_T17, HUMPHOSLIP_PEA_2_T18, and HUMPHOSTI. Table 500 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMPHOSLIP_PEA_2_node_19 of the present invention is supported by 186 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMPHOSLIP_PEA_2_T6, HUMPHOSLIP_PEA_2_T7, HUMPHOSLIP_PEA_2_T14, HUMPHOSLIP_PEA_2_T16, and HUMPHOSLIP_PEA_2_T19. Table 501 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMPHOSLIP_PEA_2_node_34 of the present invention is supported by 191 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMPHOSLIP_PEA_2_T6, HUMPHOSLIP_PEA_2_T7, HUMPHOSLIP_PEA_2_T14, HUMPHOSLIP_PEA_2_T16, HUMPHOSLIP_PEA_2_T17, HUMPHOSLIP_PEA_2_T18, and HUMPHOSTI. Table 502 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMPHOSLIP_PEA_2_node_68 of the present invention is supported by 131 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMPHOSLIP_PEA_2_T6, HUMPHOSLIP_PEA_2_T7, HUMPHOSLIP_PEA_2_T14, HUMPHOSLIP_PEA_2_T16, HUMPHOSLIP_PEA_2_T17, HUMPHOSLIP_PEA_2_T18, and HUMPHOSTI. Table 503 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMPHOSLIP_PEA_2_node_70 of the present invention is supported by 5 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMPHOSLIP_PEA_2_T6, HUMPHOSLIP_PEA_2_T7, HUMPHOSLIP_PEA_2_T14, HUMPHOSLIP_PEA_2_T16, HUMPHOSLIP_PEA_2_T17, HUMPHOSLIP_PEA_2_T18, and HUMPHOSTI. Table 504 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMPHOSLIP_PEA_2_node_75 of the present invention is supported by 14 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMPHOSLIP_PEA_2_T6, HUMPHOSLIP_PEA_2_T7, HUMPHOSLIP_PEA_2_T14, HUMPHOSLIP_PEA_2_T16, HUMPHOSLIP_PEA_2_T17, HUMPHOSLIP_PEA_2_T18, and HUMPHOSTI. Table 505 below describes the start and end positions of this segment on each transcript.

  According to an optional embodiment of the present invention, there is also provided a short segment associated with the above cluster. These segments are up to about 120 bp in length and are therefore included in the individual descriptions.

  The segment cluster HUMPHOSLIP_PEA_2_node_2 of the present invention is supported by 159 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMPHOSLIP_PEA_2_T6, HUMPHOSLIP_PEA_2_T7, HUMPHOSLIP_PEA_2_T14, HUMPHOSLIP_PEA_2_T16, HUMPHOSLIP_PEA_2_T17, HUMPHOSLIP_PEA_2_T18, and HUMPHOSTI. Table 506 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMPHOSLIP_PEA_2_node_3 according to the invention can be found in the following transcripts: HUMPHOSLIP_PEA_2_T7, HUMPHOSLIP_PEA_2_T14, HUMPHOSLIP_PEA_2_T16, HUMPHOSLIP_PEA_2_T17, HUMPHOSLIP_PEA_2_T14, Table 507 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMPHOSLIP_PEA_2_node_4 according to the invention can be found in the following transcripts: HUMPHOSLIP_PEA_2_T7, HUMPHOSLIP_PEA_2_T14, HUMPHOSLIP_PEA_2_T16, HUMPHOSLIP_PEA_2_T17, HUMPHOSLIP_PEA_2_T17_E, and Table 508 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMPHOSLIP_PEA_2_node_6 according to the invention can be found in the following transcripts: HUMPHOSLIP_PEA_2_T7, HUMPHOSLIP_PEA_2_T14, HUMPHOSLIP_PEA_2_T16, HUMPHOSLIP_PEA_2_T17, HUMPHOSLIP_PEA_2_T17_E. Table 509 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMPHOSLIP_PEA_2_node7 according to the invention can be found in the following transcripts: HUMPHOSLIP_PEA_2_T6, HUMPHOSLIP_PEA_2_T7, HUMPHOSLIP_PEA_2_T14, HUMPHOSLIP_PEA_2_T16, HUMPHOSLIP_PEA_2_T17_HITH Table 510 below describes the start and end positions of this segment on each transcript.

  Segment cluster HUMPHOSLIP_PEA_2_node_08 of the present invention, supported by 171 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMPHOSLIP_PEA_2_T6, HUMPHOSLIP_PEA_2_T7, HUMPHOSLIP_PEA_2_T14, HUMPHOSLIP_PEA_2_T16, HUMPHOSLIP_PEA_2_T17, HUMPHOSLIP_PEA_2_T18, and HUMPHOSTI. Table 511 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMPHOSLIP_PEA_2_node_9 of the present invention is supported by 168 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMPHOSLIP_PEA_2_T6, HUMPHOSLIP_PEA_2_T7, HUMPHOSLIP_PEA_2_T14, HUMPHOSLIP_PEA_2_T16, HUMPHOSLIP_PEA_2_T17, HUMPHOSLIP_PEA_2_T18, and HUMPHOSTI. Table 512 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMPHOSLIP_PEA_2_node_14 of the present invention is supported by six libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMPHOSLIP_PEA_2_T7. Table 513 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMPHOSLIP_PEA_2_node_15 according to the invention can be found in the following transcripts: HUMPHOSLIP_PEA_2_T6, HUMPHOSLIP_PEA_2_T7, HUMPHOSLIP_PEA_2_T14, HUMPHOSLIP_PEA_2_T16, HUMPHOSLIP_PEA_2_T4_T_14. Table 514 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMPHOSLIP_PEA_2_node_16 of the present invention is supported by 179 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMPHOSLIP_PEA_2_T6, HUMPHOSLIP_PEA_2_T7, HUMPHOSLIP_PEA_2_T14, HUMPHOSLIP_PEA_2_T16, HUMPHOSLIP_PEA_2_T18, and HUMPHOSLIP_PEA_2_T19. Table 515 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMPHOSLIP_PEA_2_node_17 according to the invention can be found in the following transcripts: HUMPHOSLIP_PEA_2_T6, HUMPHOSLIP_PEA_2_T7, HUMPHOSLIP_PEA_2_T14, HUMPHOSLIP_PEA_2_T16, HUMPHOSLIP_PEA_2_T4_T_14. Table 516 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMPHOSLIP_PEA_2_node_23 of the present invention is supported by 168 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMPHOSLIP_PEA_2_T6, HUMPHOSLIP_PEA_2_T7, HUMPHOSLIP_PEA_2_T14, HUMPHOSLIP_PEA_2_T16, HUMPHOSLIP_PEA_2_T17, HUMPHOSLIP_PEA_2_T18, and HUMPHOSTI. Table 517 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMPHOSLIP_PEA_2_node_24 according to the invention can be found in the following transcripts: HUMPHOSLIP_PEA_2_T6, HUMPHOSLIP_PEA_2_T7, HUMPHOSLIP_PEA_2_T14, HUMPHOSLIP_PEA_2_T16, HUMPHOSLIP_PEA_2_T 、 、 Table 518 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMPHOSLIP_PEA_2_node_25 of the present invention is supported by 5 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMPHOSLIP_PEA_2_T14 and HUMPHOSLIP_PEA_2_T18. Table 519 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMPHOSLIP_PEA_2_node_26 of the present invention is supported by 163 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMPHOSLIP_PEA_2_T6, HUMPHOSLIP_PEA_2_T7, HUMPHOSLIP_PEA_2_T14, HUMPHOSLIP_PEA_2_T16, HUMPHOSLIP_PEA_2_T17, HUMPHOSLIP_PEA_2_T18, and HUMPHOSTI. Table 520 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMPHOSLIP_PEA_2_node_2 according to the invention can be found in the following transcripts: HUMPHOSLIP_PEA_2_T6, HUMPHOSLIP_PEA_2_T7, HUMPHOSLIP_PEA_2_T14, HUMPHOSLIP_PEA_2_T17, HUMPHOSLIP_PEA_2_T14, Table 521 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMPHOSLIP_PEA_2_node_30 of the present invention is supported by 181 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMPHOSLIP_PEA_2_T6, HUMPHOSLIP_PEA_2_T7, HUMPHOSLIP_PEA_2_T14, HUMPHOSLIP_PEA_2_T16, HUMPHOSLIP_PEA_2_T17, HUMPHOSLIP_PEA_2_T18, and HUMPHOSTI. Table 522 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMPHOSLIP_PEA_2_node_33 of the present invention is supported by 173 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMPHOSLIP_PEA_2_T6, HUMPHOSLIP_PEA_2_T7, HUMPHOSLIP_PEA_2_T14, HUMPHOSLIP_PEA_2_T16, HUMPHOSLIP_PEA_2_T17, HUMPHOSLIP_PEA_2_T18, and HUMPHOSTI. Table 523 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMPHOSLIP_PEA_2_node_36 of the present invention is supported by 163 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMPHOSLIP_PEA_2_T6, HUMPHOSLIP_PEA_2_T7, HUMPHOSLIP_PEA_2_T14, HUMPHOSLIP_PEA_2_T16, HUMPHOSLIP_PEA_2_T17, HUMPHOSLIP_PEA_2_T18, and HUMPHOSTI. Table 524 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMPHOSLIP_PEA_2_node_37 according to the invention can be found in the following transcripts: HUMPHOSLIP_PEA_2_T6, HUMPHOSLIP_PEA_2_T7, HUMPHOSLIP_PEA_2_T14, HUMPHOSLIP_PEA_2_T16, HUMPHOSLIP_PEA_2_T UT Table 525 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMPHOSLIP_PEA_2_node_39 of the present invention is supported by 166 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMPHOSLIP_PEA_2_T6, HUMPHOSLIP_PEA_2_T7, HUMPHOSLIP_PEA_2_T14, HUMPHOSLIP_PEA_2_T16, HUMPHOSLIP_PEA_2_T17, HUMPHOSLIP_PEA_2_T18, and HUMPHOSTI. Table 525 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMPHOSLIP_PEA_2_node_40 of the present invention is supported by 199 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMPHOSLIP_PEA_2_T6, HUMPHOSLIP_PEA_2_T7, HUMPHOSLIP_PEA_2_T14, HUMPHOSLIP_PEA_2_T16, HUMPHOSLIP_PEA_2_T17, HUMPHOSLIP_PEA_2_T18, and HUMPHOSTI. Table 526 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMPHOSLIP_PEA_2_node_41 of the present invention is supported by 186 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMPHOSLIP_PEA_2_T6, HUMPHOSLIP_PEA_2_T7, HUMPHOSLIP_PEA_2_T14, HUMPHOSLIP_PEA_2_T16, HUMPHOSLIP_PEA_2_T17, HUMPHOSLIP_PEA_2_T18, and HUMPHOSTI. Table 527 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMPHOSLIP_PEA_2_node_42 according to the invention can be found in the following transcripts: HUMPHOSLIP_PEA_2_T6, HUMPHOSLIP_PEA_2_T7, HUMPHOSLIP_PEA_2_T14, HUMPHOSLIP_PEA_2_T16, HUMPHOSLIP_PEA_2_T4 Table 528 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMPHOSLIP_PEA_2_node_44 of the present invention is supported by 185 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMPHOSLIP_PEA_2_T6, HUMPHOSLIP_PEA_2_T7, HUMPHOSLIP_PEA_2_T14, HUMPHOSLIP_PEA_2_T16, HUMPHOSLIP_PEA_2_T17, HUMPHOSLIP_PEA_2_T18, and HUMPHOSTI. Table 529 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMPHOSLIP_PEA_2_node_45 of the present invention is supported by 197 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMPHOSLIP_PEA_2_T6, HUMPHOSLIP_PEA_2_T7, HUMPHOSLIP_PEA_2_T14, HUMPHOSLIP_PEA_2_T16, HUMPHOSLIP_PEA_2_T17, HUMPHOSLIP_PEA_2_T18, and HUMPHOSTI. Table 530 below lists the start and end positions of this segment on each transcript.

  The segment cluster HUMPHOSLIP_PEA_2_node_47 of the present invention is supported by 223 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMPHOSLIP_PEA_2_T6, HUMPHOSLIP_PEA_2_T7, HUMPHOSLIP_PEA_2_T14, HUMPHOSLIP_PEA_2_T16, HUMPHOSLIP_PEA_2_T17, HUMPHOSLIP_PEA_2_T18, and HUMPHOSTI. Table 531 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMPHOSLIP_PEA_2_node_51 of the present invention can be found in the following transcripts: HUMPHOSLIP_PEA_2_T6, HUMPHOSLIP_PEA_2_T7, HUMPHOSLIP_PEA_2_T14, HUMPHOSLIP_PEA_2_T16, HUMPHOSLIP_PEA_2_T 、 、 Table 532 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMPHOSLIP_PEA_2_node_52 of the present invention is supported by 235 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMPHOSLIP_PEA_2_T6, HUMPHOSLIP_PEA_2_T7, HUMPHOSLIP_PEA_2_T14, HUMPHOSLIP_PEA_2_T16, HUMPHOSLIP_PEA_2_T17, HUMPHOSLIP_PEA_2_T18, and HUMPHOSTI. Table 533 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMPHOSLIP_PEA_2_node_53 of the present invention is supported by 5 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMPHOSLIP_PEA_2_T19. Table 534 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMPHOSLIP_PEA_2_node_54 of the present invention is supported by 236 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMPHOSLIP_PEA_2_T6, HUMPHOSLIP_PEA_2_T7, HUMPHOSLIP_PEA_2_T14, HUMPHOSLIP_PEA_2_T16, HUMPHOSLIP_PEA_2_T17, HUMPHOSLIP_PEA_2_T18, and HUMPHOSTI. Table 535 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMPHOSLIP_PEA_2_node_55 of the present invention is supported by 232 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMPHOSLIP_PEA_2_T6, HUMPHOSLIP_PEA_2_T7, HUMPHOSLIP_PEA_2_T14, HUMPHOSLIP_PEA_2_T16, HUMPHOSLIP_PEA_2_T17, HUMPHOSLIP_PEA_2_T18, and HUMPHOSTI. Table 536 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMPHOSLIP_PEA_2_node_58 of the present invention can be found in the following transcripts: HUMPHOSLIP_PEA_2_T6, HUMPHOSLIP_PEA_2_T7, HUMPHOSLIP_PEA_2_T14, HUMPHOSLIP_PEA_2_T16, HUMPHOSLIP_PEA_2_T 、 、 Table 537 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMPHOSLIP_PEA_2_node_59 of the present invention is supported by 230 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMPHOSLIP_PEA_2_T6, HUMPHOSLIP_PEA_2_T7, HUMPHOSLIP_PEA_2_T14, HUMPHOSLIP_PEA_2_T16, HUMPHOSLIP_PEA_2_T17, HUMPHOSLIP_PEA_2_T18, and HUMPHOSTI. Table 538 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMPHOSLIP_PEA_2_node_60 according to the invention can be found in the following transcripts: HUMPHOSLIP_PEA_2_T6, HUMPHOSLIP_PEA_2_T7, HUMPHOSLIP_PEA_2_T14, HUMPHOSLIP_PEA_2_T16, HUMPHOSLIP_PEA_2_T 、 Table 539 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMPHOSLIP_PEA_2_node_61 according to the invention can be found in the following transcripts: HUMPHOSLIP_PEA_2_T6, HUMPHOSLIP_PEA_2_T7, HUMPHOSLIP_PEA_2_T14, HUMPHOSLIP_PEA_2_T16, HUMPHOSLIP_PEA_2_T UT Table 540 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMPHOSLIP_PEA_2_node_62 according to the invention can be found in the following transcripts: HUMPHOSLIP_PEA_2_T6, HUMPHOSLIP_PEA_2_T7, HUMPHOSLIP_PEA_2_T14, HUMPHOSLIP_PEA_2_T16, HUMPHOSLIP_PEA_2_T 、 Table 541 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMPHOSLIP_PEA_2_node_63 according to the invention can be found in the following transcripts: HUMPHOSLIP_PEA_2_T6, HUMPHOSLIP_PEA_2_T7, HUMPHOSLIP_PEA_2_T14, HUMPHOSLIP_PEA_2_T16, HUMPHOSLIP_PEA_2_T 、 HO Table 542 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMPHOSLIP_PEA_2_node_64 according to the invention can be found in the following transcripts: HUMPHOSLIP_PEA_2_T6, HUMPHOSLIP_PEA_2_T7, HUMPHOSLIP_PEA_2_T14, HUMPHOSLIP_PEA_2_T16, HUMPHOSLIP_PEA_2_T UT Table 543 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMPHOSLIP_PEA_2_node_65 according to the invention can be found in the following transcripts: HUMPHOSLIP_PEA_2_T6, HUMPHOSLIP_PEA_2_T7, HUMPHOSLIP_PEA_2_T14, HUMPHOSLIP_PEA_2_T16, HUMPHOSLIP_PEA_2_T 、 、 Table 544 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMPHOSLIP_PEA_2_node_66 of the present invention is supported by 180 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMPHOSLIP_PEA_2_T6, HUMPHOSLIP_PEA_2_T7, HUMPHOSLIP_PEA_2_T14, HUMPHOSLIP_PEA_2_T16, HUMPHOSLIP_PEA_2_T17, HUMPHOSLIP_PEA_2_T18, and HUMPHOSTI. Table 545 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMPHOSLIP_PEA_2_node_67 according to the invention can be found in the following transcripts: HUMPHOSLIP_PEA_2_T6, HUMPHOSLIP_PEA_2_T7, HUMPHOSLIP_PEA_2_T14, HUMPHOSLIP_PEA_2_T16, HUMPHOSLIP_PEA_2_T UT 、 Table 546 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMPHOSLIP_PEA_2_node_69 according to the invention can be found in the following transcripts: HUMPHOSLIP_PEA_2_T6, HUMPHOSLIP_PEA_2_T7, HUMPHOSLIP_PEA_2_T14, HUMPHOSLIP_PEA_2_T16, HUMPHOSLIP_PEA_2_T UT Table 547 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMPHOSLIP_PEA_2_node_71 according to the invention can be found in the following transcripts: Table 548 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMPHOSLIP_PEA_2_node_72 of the present invention is supported by seven libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMPHOSLIP_PEA_2_T6, HUMPHOSLIP_PEA_2_T7, HUMPHOSLIP_PEA_2_T14, HUMPHOSLIP_PEA_2_T16, HUMPHOSLIP_PEA_2_T17, HUMPHOSLIP_PEA_2_T18, and HUMPHOSTI. Table 549 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMPHOSLIP_PEA_2_node_73 of the present invention is supported by 5 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMPHOSLIP_PEA_2_T6, HUMPHOSLIP_PEA_2_T7, HUMPHOSLIP_PEA_2_T14, HUMPHOSLIP_PEA_2_T16, HUMPHOSLIP_PEA_2_T17, HUMPHOSLIP_PEA_2_T18, and HUMPHOSTI. Table 550 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMPHOSLIP_PEA_2_node_74 of the present invention is supported by 10 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMPHOSLIP_PEA_2_T6, HUMPHOSLIP_PEA_2_T7, HUMPHOSLIP_PEA_2_T14, HUMPHOSLIP_PEA_2_T16, HUMPHOSLIP_PEA_2_T17, HUMPHOSLIP_PEA_2_T18, and HUMPHOSTI. Table 551 below describes the start and end positions of this segment on each transcript.

Mutated protein alignment against previously known proteins:
Sequence name: PLTP_HUMAN

Sequence documentation:

Alignment of: HUMPHOSLIP_PEA_2_P10 x PLTP_HUMAN ..

Alignment segment 1/1:

Quality: 3716.00 Escore: 0
Matching length: 398 Total length: 493
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 80.73 Total Percent Identity: 80.73
Gaps: 1

Alignment:
....
1 MALFGALFALLAGAHAEFPGCKIRVTSKALEVKQEGLRFLEQELETIT 50
||||||||||||||||||||||||||||||||||||||||
1 MALFGALFALLAGAHAEFPGCKIRVTSKALEVKQEGLRFLEQELETIT 50
....
51 IPDLRGKEGHFYYNISE ......................................... 67
||||||||||||||||
51 IPDLRGKEGYYNISEEVKVTELQLTSSELDFQPQELMLQITNASLGLR 100
....
67 ...................................................... . 67

101 FRRQLLYWFFYDGGYINASAEGVSTIRTGLELSRDPAGRMK VSNVSCQASV 150
....
68 ............ KVYDFLSTF ITGMMRFLNQQICPVLYHAGTVLLNSLL 105
|||||||||||||||||||||||||||||||||||
151 SRMHAAFGGTFKKVYDFLSTFITSGMRFLNQQICPVLYHAGTVLLNSLL 200
....
106 DTVPVRSSVDELVGIDYSLKMPDVASTSLNDLMGAFFPLTERNWSLPN 155
||||||||||||||||||||||||||||||||||||||||
201 DTVPVRSSVDELVGIDYSLKMPDVASSTNLDMDFRGAFFPLTERNWSLPN 250
....
156 RAVEPQLQEEERMVYVAFSEFFFDSAMESYFRAGALQLLLVGDKVPHDLD 205
||||||||||||||||||||||||||||||||||||||||
251 RAVEPQLQEEERMVYVAFSEFFFDSAMESYFRAGALQLLLVGDKVPHDLD 300
....
206 MLLRATYFGSIVLLSPAVIDSPLKLELLRVLAPPRCTIKPSGTTISV TASV 255
||||||||||||||||||||||||||||||||||||||||
301 MLLRATYFGSIVLLSPAVIDSPLKLELLVLAPPRCTIKPSGTTISVTASV 350
....
256 TIALVPPDQPEVQLSSMTMDARLSAKMALRGKALRTQLDLRRFRIYSNHS 305
||||||||||||||||||||||||||||||||||||||||
351 TIALVPPDQPEVQLSSMTM DARLSAKMALRGKALRTQLDLRRFRIYSNHS 400
....
306 ALESLALIPLQAPLKTMLQIGVMPMLNERTWRGVQIPLPEGINFVHEVVT 355
||||||||||||||||||||||||||||||||||||||||
401 ALESLALIPLQAPLKTMLQIGVMPMLNERTWRGVQIPLPEGINFVHEVVT 450
....
356 NHAGFLTIGADLHFAKGLREVIEKNRPADVRASTAPTPSTAAV 398
|||||||||||||||||||||||||||||||||||||
451 NHAGFLTIGADLHFAKGLREVIEKNRPADVRASTAPTPSTAAV 493






Sequence name: PLTP_HUMAN

Sequence documentation:

Alignment of: HUMPHOSLIP_PEA_2_P12 x PLTP_HUMAN ..

Alignment segment 1/1:

Quality: 4101.00 Escore: 0
Matching length: 427 Total length: 427
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MALFGALFALLAGAHAEFPGCKIRVTSKALEVKQEGLRFLEQELETIT 50
||||||||||||||||||||||||||||||||||||||||
1 MALFGALFALLAGAHAEFPGCKIRVTSKALEVKQEGLRFLEQELETIT 50
....
51 IPDLRGKEGYYNISEEVKVTELQLTSSELDFQPQELMLQITNASLGLR 100
||||||||||||||||||||||||||||||||||||||||
51 IPDLRGKEGYYNISEEVKVTELQLTSSELDFQPQELMLQITNASLGLR 100
....
101 FRRQLLYWFFYDGGYINASAEGVSTIRTGLELSRDPAGRMK VSNVSCQASV 150
||||||||||||||||||||||||||||||||||||||||
101 FRRQLLYWFFYDGGYINASAEGVSTIRTGLELSRDPAGRMK VSNVSCQASV 150
....
151 SRMHAAFGGTFKKVYDFLSTFITSGMRFLNQQICPVLYHAGTVLLNSLL 200
||||||||||||||||||||||||||||||||||||||||
151 SRMHAAFGGTFKKVYDFLSTFITSGMRFLNQQICPVLYHAGTVLLNSLL 200
....
201 DTVPVRSSVDELVGIDYSLKMPDVASSTNLDMDFRGAFFPLTERNWSLPN 250
||||||||||||||||||||||||||||||||||||||||
201 DTVPVRSSVDELVGIDYSLKMPDVASSTNLDMDFRGAFFPLTERNWSLPN 250
....
251 RAVEPQLQEEERMVYVAFSEFFFDSAMESYFRAGALQLLLVGDKVPHDLD 300
||||||||||||||||||||||||||||||||||||||||
251 RAVEPQLQEEERMVYVAFSEFFFDSAMESYFRAGALQLLLVGDKVPHDLD 300
....
301 MLLRATYFGSIVLLSPAVIDSPLKLELLVLAPPRCTIKPSGTTISVTASV 350
||||||||||||||||||||||||||||||||||||||||
301 MLLRATYFGSIVLLSPAVIDSPLKLELLVLAPPRCTIKPSGTTISVTASV 350
....
351 TIALVPPDQPEVQLSSMTM DARLSAKMALRGKALRTQLDLRRFRIYSNHS 400
||||||||||||||||||||||||||||||||||||||||
351 TIALVPPDQPEVQLSSMTM DARLSAKMALRGKALRTQLDLRRFRIYSNHS 400
.
401 ALESLALIPLQAPLKTMLQIGVMPMLN 427
|||||||||||||||||||||||||
401 ALESLALIPLQAPLKTMLQIGVMPMLN 427






Sequence name: PLTP_HUMAN

Sequence documentation:

Alignment of: HUMPHOSLIP_PEA_2_P31 x PLTP_HUMAN ..

Alignment segment 1/1:

Quality: 639.00 Escore: 0
Matching length: 67 Total length: 67
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MALFGALFALLAGAHAEFPGCKIRVTSKALEVKQEGLRFLEQELETIT 50
||||||||||||||||||||||||||||||||||||||||
1 MALFGALFALLAGAHAEFPGCKIRVTSKALEVKQEGLRFLEQELETIT 50
.
51 IPDLRGKEGHFYYNISE 67
||||||||||||||||
51 IPDLRGKEGHFYYNISE 67






Sequence name: PLTP_HUMAN

Sequence documentation:

Alignment of: HUMPHOSLIP_PEA_2_P33 x PLTP_HUMAN ..

Alignment segment 1/1:

Quality: 1767.00 Escore: 0
Matching length: 184 Total length: 184
Matching Percent Similarity: 100.00 Matching Percent Identity: 99.46
Total Percent Similarity: 100.00 Total Percent Identity: 99.46
Gaps: 0

Alignment:
....
1 MALFGALFALLAGAHAEFPGCKIRVTSKALEVKQEGLRFLEQELETIT 50
||||||||||||||||||||||||||||||||||||||||
1 MALFGALFALLAGAHAEFPGCKIRVTSKALEVKQEGLRFLEQELETIT 50
....
51 IPDLRGKEGYYNISEEVKVTELQLTSSELDFQPQELMLQITNASLGLR 100
||||||||||||||||||||||||||||||||||||||||
51 IPDLRGKEGYYNISEEVKVTELQLTSSELDFQPQELMLQITNASLGLR 100
....
101 FRRQLLYWFFYDGGYINASAEGVSTIRTGLELSRDPAGRMK VSNVSCQASV 150
||||||||||||||||||||||||||||||||||||||||
101 FRRQLLYWFFYDGGYINASAEGVSTIRTGLELSRDPAGRMK VSNVSCQASV 150
....
151 SRMHAAFGGTFKKVYDFLSTFITSMRFLNQQV 184
|||||||||||||||||||||||||||: |
151 SRMHAAFGGTFKKVYDFLSTFITSMRFLNQQI 184






Sequence name: PLTP_HUMAN

Sequence documentation:

Alignment of: HUMPHOSLIP_PEA_2_P34 x PLTP_HUMAN ..

Alignment segment 1/1:

Quality: 1971.00 Escore: 0
Matching length: 205 Total length: 205
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MALFGALFALLAGAHAEFPGCKIRVTSKALEVKQEGLRFLEQELETIT 50
||||||||||||||||||||||||||||||||||||||||
1 MALFGALFALLAGAHAEFPGCKIRVTSKALEVKQEGLRFLEQELETIT 50
....
51 IPDLRGKEGYYNISEEVKVTELQLTSSELDFQPQELMLQITNASLGLR 100
||||||||||||||||||||||||||||||||||||||||
51 IPDLRGKEGYYNISEEVKVTELQLTSSELDFQPQELMLQITNASLGLR 100
....
101 FRRQLLYWFFYDGGYINASAEGVSTIRTGLELSRDPAGRMK VSNVSCQASV 150
||||||||||||||||||||||||||||||||||||||||
101 FRRQLLYWFFYDGGYINASAEGVSTIRTGLELSRDPAGRMK VSNVSCQASV 150
....
151 SRMHAAFGGTFKKVYDFLSTFITSGMRFLNQQICPVLYHAGTVLLNSLL 200
||||||||||||||||||||||||||||||||||||||||
151 SRMHAAFGGTFKKVYDFLSTFITSGMRFLNQQICPVLYHAGTVLLNSLL 200

201 DTVPV 205
||||||
201 DTVPV 205






Sequence name: PLTP_HUMAN

Sequence documentation:

Alignment of: HUMPHOSLIP_PEA_2_P35 x PLTP_HUMAN ..

Alignment segment 1/1:

Quality: 1158.00 Escore: 0
Matching length: 132 Total length: 184
Matching Percent Similarity: 100.00 Matching Percent Identity: 98.48
Total Percent Similarity: 71.74 Total Percent Identity: 70.65
Gaps: 1

Alignment:
....
1 MALFGALFALLAGAHAEFPGCKIRVTSKALEVKQEGLRFLEQELETIT 50
||||||||||||||||||||||||||||||||||||||||
1 MALFGALFALLAGAHAEFPGCKIRVTSKALEVKQEGLRFLEQELETIT 50
....
51 IPDLRGKEGYYNISEEVKVTELQLTSSELDFQPQELMLQITNASLGLR 100
||||||||||||||||||||||||||||||||||||||||
51 IPDLRGKEGYYNISEEVKVTELQLTSSELDFQPQELMLQITNASLGLR 100
....
101 FRRQLLYWFL ......................................... 110
||||||||: |
101 FRRQLLYWFFYDGGYINASAEGVSTIRTGLELSRDPAGRMK VSNVSCQASV 150
....
111 ............ KVYDFLSTFITSMRFLNQQV 132
||||||||||||||||||: |
151 SRMHAAFGGTFKKVYDFLSTFITSMRFLNQQI 184

Description of cluster AI076020 Cluster AI076020 features one transcript and eight segments of interest, the names of which are shown in Tables 552 and 553, respectively, and the sequence itself is shown at the end of the application. Selected protein variants are shown in Table 554.

  These sequences are variants of C1q-related factor precursor (SwissProt accession identifier C1RF_HUMAN) (SEQ ID NO: 1434), which is a known protein, referred to herein as a previously known protein.

  The sequence of the protein C1q related factor precursor is shown at the end of the application as “C1q related factor precursor amino acid sequence”.

  The following GO annotation applies to previously known proteins. The following annotations were found: behavior of the moving organ, which is an annotation related to biological processes.

  GO assignments can be made at one or more http: // www. expasy. SwissProt / TremBl Protein knowledgebase available from ch / sprot / or http: // www. ncbi. nlm. nih. Depends on Locuslink available from gov / projects / LocusLink /.

  Cluster AI076020 can be used as a diagnostic marker by overexpression of transcripts of this cluster in cancer. The expression of such transcripts in normal tissues is also shown by the method previously described. The terms "numbers" in the right column of the table and the numbers on the y-axis of FIG. 31 refer to the weighted expression of ESTs in each category as "ppm" (for ESTs of a particular cluster in this category by ppm Ratio of expression to expression of all ESTs).

  In general, as shown for the histograms in FIG. 31 and Table 555, the following results were obtained. This cluster was overexpressed (at least at minimal levels) in the following pathological conditions: a mixture of malignant brain tumors and malignant tumors from different tissues.

  As mentioned above, cluster AI076020 is characterized by one transcript as listed in Table 1 above. These transcripts encode proteins which are variants of the protein C1q related factor precursor. A description of each mutein of the invention is provided herein.

  The mutein AI076020_P1 according to the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript AI076020_T0. The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein AI076020_P1 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing the other amino acids, and listing the other amino acids, as shown in Table 557) It indicates whether it is known and the presence of a known SNP in the mutant protein AI076020_P1 sequence supports the deduced sequence of this mutant protein according to the invention).

  The mutein AI076020_P1 is encoded by the following transcript: AI076020_T0 (sequences shown at the end of the application). The code portion of transcript AI076020_T0 is shown in bold, starting at position 261 and ending at position 1034. The transcript also has the following SNPs listed in Table 558 (indicating its position on the nucleotide sequence and listing another nucleic acid, the last column indicating whether the SNP is known, the mutein AI076020_P1 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  As mentioned above, cluster AI076020 is characterized by the eight segments listed in Table 2 above, the sequence of which is shown at the end of the application. These segments are part of the nucleic acid sequence, which are of particular interest and are individually described herein. A description of each segment of the invention is provided herein.

  The segment cluster AI076020_node_0 of the present invention is supported by 28 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: AI076020_T0. Table 559 below describes the start and end positions of this segment on each transcript.

  Microarray (chip) data for this segment is also available, as follows. As described above, with respect to the clusters themselves, different oligonucleotides were tested for differential expression in different disease states, in particular cancer. The following oligonucleotides were found to reach this segment (for lung cancer) (shown in Table 560).

  The segment cluster AI076020_node_3 of the present invention is supported by 30 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: AI076020_T0. Table 561 below describes the start and end positions of this segment on each transcript.

  The segment cluster AI076020_node_8 of the present invention is supported by 35 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: AI076020_T0. Table 562 below describes the start and end positions of this segment on each transcript.

  According to an optional embodiment of the present invention, there is also provided a short segment associated with the above cluster. These segments are up to about 120 bp in length and are therefore included in the individual descriptions.

  The segment cluster AI076020_node_1 of the present invention is supported by 19 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: AI076020_T0. Table 563 below describes the start and end position of this segment on each transcript.

  The segment cluster AI076020_node_4 of the present invention is supported by 28 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: AI076020_T0. Table 564 below describes the start and end positions of this segment on each transcript.

  The segment cluster AI076020_node_5 of the present invention is supported by 31 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: AI076020_T0. Table 565 below describes the start and end positions of this segment on each transcript.

  The segment cluster AI076020_node_6 of the present invention is supported by 32 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: AI076020_T0. Table 566 below describes the start and end positions of this segment on each transcript.

  The segment cluster AI076020_node_7 of the present invention is supported by 33 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: AI076020_T0. Table 567 below describes the start and end positions of this segment on each transcript.

Description of Cluster T23580 Cluster T23580 is characterized by one transcript and five segments of interest, the names of which are shown in Tables 568 and 569 respectively, and the sequence itself is shown at the end of the application. Selected protein variants are shown in Table 570.

  These sequences are referred to herein as previously known proteins, and are known proteins of which the previous SwissProt accession identifier is also NP25_HUMAN, a neuroprotein NP25 (SwissProt accession identifier TAG3_HUMAN, synonymous neuroprotein) 22, NP22, also known as Transgelin-3 (SEQ ID NO: 1433).

  The sequence of protein neuroprotein NP25 is shown at the end of the application as "neuroprotein NP25 amino acid sequence".

  The following GO annotation applies to previously known proteins. The following annotations have been found: Central nervous system development, which is an annotation related to biological processes.

  GO assignments can be made at one or more http: // www. expasy. SwissProt / TremBl Protein knowledgebase available from ch / sprot / or http: // www. ncbi. nlm. nih. Depends on Locuslink available from gov / projects / LocusLink /.

  For this cluster, at least one oligonucleotide was found to demonstrate overexpression of the cluster, but not in at least one transcript / segment listed below. Microarray (chip) data for this segment is also available, as follows. As noted above, different oligonucleotides were tested for differential expression in different disease states, in particular cancer. The following oligonucleotides were found to reach this cluster for lung cancer but not the other segments / transcripts below (shown in Table 571).

  As mentioned above, cluster T23580 is characterized by one transcript as listed in Table 1 above. These transcripts encode a protein that is a mutated form of protein neuroprotein NP25. A description of each mutein of the invention is provided herein.

  The mutein T23580_P5 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript T23580_T10. The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is considered to be secreted as it is presumed that this protein has a signal peptide by one of two signal peptide estimation programs (HMM: Signal peptide, NN: NO).

  The mutein T23580_P5 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing the other amino acids, and listing the other amino acids, and the last It is shown whether it is known and the presence of a known SNP in the mutein T23580_P5 sequence supports the deduced sequence of this mutein of the invention).

  The mutein T23580_P5 is encoded by the following transcript: T23580_T10 (sequences shown at the end of the application). The code portion of transcript T23580_T10 is shown in bold and this code portion starts at position 1066 and ends at position 1485. The transcript also has the following SNPs listed in Table 573 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein T23580_P5 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  As mentioned above, cluster T23 580 is characterized by the five segments listed in Table 2 above, the sequence of which is shown at the end of the application. These segments are part of the nucleic acid sequence, which are of particular interest and are individually described herein. A description of each segment of the invention is provided herein.

  The segment cluster T23580_node_17 of the present invention is supported by 10 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T23580_T10. Table 574 below describes the start and end positions of this segment on each transcript.

  The segment cluster T23580_node_18 of the present invention is supported by 102 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T23580_T10. Table 575 below describes the start and end positions of this segment on each transcript.

  The segment cluster T23580_node_21 of the present invention is supported by 79 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T23580_T10. Table 576 below describes the start and end positions of this segment on each transcript.

  According to an optional embodiment of the present invention, there is also provided a short segment associated with the above cluster. These segments are up to about 120 bp in length and are therefore included in the individual descriptions.

  The segment cluster T23580_node_19 of the invention can be found in the following transcript: T23580_T10. Table 577 below describes the start and end positions of this segment on each transcript.

  The segment cluster T23580_node_20 according to the invention can be found in the following transcript: T23580_T10. Table 578 below describes the start and end positions of this segment on each transcript.

Description of Cluster M79217 Cluster M79217 is characterized by 6 transcripts and 32 segments of interest, the names of which are shown in Tables 579 and 580, respectively, and the sequence itself is shown at the end of the application. Selected protein variants are shown in Table 581.

  These sequences are known proteins Exostosin-like 3 (SwissProt accession identifier EXL3_HUMAN), which is a known protein previously known in the present specification, the synonym EC 2.4.1.223, glucuronyl-galactosyl- Proteoglycan 4-.alpha.-N-acetylglucosaminyltransferase, putative tumor suppressor protein EXTL3, multiple exostocin-like protein 3, hereditary multiple exospermatosis gene isolog (also known as EXT related protein 1) (SEQ ID NO: 1436).

  The protein exostocin-like 3 is known or is considered to have the following function: Possible of glycosyltransferases (by similarity). The sequence of protein exostocin-like 3 is shown at the end of the application as "exostocin-like 3 amino acid sequence". Localization of the protein exostocin-like 3 is considered to be a type II membrane protein. Endoplasmic reticulum.

  The following GO annotation applies to previously known proteins. The following annotations were found: growth and / or maintenance of cells that are related to biological processes, transferases that are annotations related to molecular function, transferrin glycosyl groups, and cell components Annotated endoplasmic reticulum, integral membrane protein.

  GO assignments can be made at one or more http: // www. expasy. SwissProt / TremBl Protein knowledgebase available from ch / sprot / or http: // www. ncbi. nlm. nih. Depends on Locuslink available from gov / projects / LocusLink /.

  As mentioned above, cluster M79217 is characterized by the six transcripts listed in Table 1 above. These transcripts encode a protein which is a mutated form of the protein exostocin-like 3. A description of each mutein of the invention is provided herein.

  The mutein M79217_PEA_1_P1 according to the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript M79217_PEA_1_T1. An alignment to a known protein (exostocin-like 3) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of the comparison between M79217_PEA_1_P1 and BAA 25445 (SEQ ID NO: 1437) Corresponding to amino acids 13-931 of BAA25445, corresponding to amino acids 1 to 919 of M79217_PEA_1_P1 MTGYTMLRNGGAGNGGQTCMLRWSNRIRLTWLSFTLFVILVFFPLIAHYYLTTLDEADEAGKRIFGPRVGNELCEVKHVLDLCRIRESVSEELLQLEAKRQELNSEIAKLNLKIEACKKSIENAKQDLLQLKNVISQTEHSYKELMAQNQPKLSLPIRLLPEKDDAGLPPPKATRGCRLHNCFDYSRCPLTSGFPVYVYDSDQFVFGSYLDPLVKQAFQATARANVYVTENADIACLYVILVGEMQEPVVLRPAELEKQLYSLPHWRTDGHNHVIINL RKSDTQNLLYNVSTGRAMVAQSTFYTVQYRPGFDLVVSPLVHAMSEPNFMEIPPQVPVKRKYLFTFQGEKIESLRSSLQEARSFEEEMEGDPPADYDDRIIATLKAVQDSKLDQVLVEFTCKNQPKPSLPTEWALCGEREDRLELLKLSTFALIITPGDPRLVISSGCATRLFEALEVGAVPVVLGEQVQLPYQDMLQWNEAALVVPKPRVTEVHFLLRSLSDSDLLAMRRQGRFLWETYFSTADSIFNTVLAMIRTRIQIPAAPIREEAAAEIPHRSGKAAGTDPNMADNGDLDLGPVETEPPYASPRYLRNFTLTVTDFYRSWNCAPGPF LFPHTPFDPVLPSEAKFLGSGTGFRPIGGGAGGSGKEFQAALGGNVPREQFTVVMLTYEREEVLMNSLERLNGLPYLNKVVVVWNSPKLPSEDLLWPDIGVPIMVVRTEKNSLNNRFLPWNEIETEAILSIDDDAHLRHDEIMFGFRVWREARDRIVGFPGRYHAWDIPHQSWLYNSNYSCELSMVLTGAAFFHKYYAYLYSYVMPQAIRDMVDEYINCEDIAMNFLVSHITRKPPIKVTSRWTFRCPGCPQALSHDDSHFHERHKCINFFVKVYGYMPLLYTQFRVDSVLFKTRLPHDKTKCFKFI and containing at least 90% homologous first amino acid sequence, M An isolated chimeric polypeptide encoding 79217_PEA_1_P1.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: membrane. Protein localization is considered to be membrane as the Signalp_hmm software presumes that this protein has a signal anchor region.

  The mutein M79217_PEA_1_P1 is encoded by the following transcript: M79217_PEA_1_T1 (sequences shown at the end of the application). The coding portion of the transcript M79217_PEA_1_T1 is shown in bold, starting from position 1074 and ending at position 3830. The transcript also has the following SNPs listed in Table 582 (showing its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein M79217_PEA_1_P1 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein M79217_PEA_1_P2 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript M79217_PEA_1_T8. An alignment to a known protein (exostocin-like 3) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between M79217_PEA_1_P2 and EXL3_HUMAN 1. Corresponding to amino acids 1 to 807 of EXL3_HUMAN, corresponding to amino acids 1 to 807 of M79217_PEA_1_P2 MTGYTMLRNGGAGNGGQTCMLRWSNRIRLTWLSFTLFVILVFFPLIAHYYLTTLDEADEAGKRIFGPRVGNELCEVKHVLDLCRIRESVSEELLQLEAKRQELNSEIAKLNLKIEACKKSIENAKQDLLQLKNVISQTEHSYKELMAQNQPKLSLPIRLLPEKDDAGLPPPKATRGCRLHNCFDYSRCPLTSGFPVYVYDSDQFVFGSYLDPLVKQAFQATARANVYVTENADIACLYVILVGEMQEPVVLRPAELEKQLYSLPHWRTDGHNHVIIN SRKSDTQNLLYNVSTGRAMVAQSTFYTVQYRPGFDLVVSPLVHAMSEPNFMEIPPQVPVKRKYLFTFQGEKIESLRSSLQEARSFEEEMEGDPPADYDDRIIATLKAVQDSKLDQVLVEFTCKNQPKPSLPTEWALCGEREDRLELLKLSTFALIITPGDPRLVISSGCATRLFEALEVGAVPVVLGEQVQLPYQDMLQWNEAALVVPKPRVTEVHFLLRSLSDSDLLAMRRQGRFLWETYFSTADSIFNTVLAMIRTRIQIPAAPIREEAAAEIPHRSGKAAGTDPNMADNGDLDLGPVETEPPYASPRYLRNFTLTVTDFYRSWNCAPGP The first amino acid sequence at least 90% homologous to EichieruefuPieichitiPiefudiPibuieruPiesuieikeiefuerujiesujitijiefuaruPiaijijijieijijiesujikeiiefukyueieierujijienubuiPiaruikyuefutibuibuiemuerutiwaiiaruiibuieruemuenuesueruiarueruenujieruPiwaieruenukeibuibuibuibuidaburyuenuesuPikeieruPiesuidieruerudaburyuPidiaijibuiPiaiemubuibuiarutiikeienuesueruenuenuaruefueruPidaburyuenuiaiitiieiaieruesuaidididieieichieruarueichidiiaiemuefujiefuarubuidaburyuaruieiarudiaruaibuijiefuPijiaruwaieichieidaburyudiaipehaQSWLYNSNYSCELSMVLTGAAFFHK, corresponding to amino acids 820-919 of EXL3_HUMAN, corresponding to amino acids 808-907 of M79217_PEA_1_P2 AIRDMVDEYINCEDIAMNFLVSHITRKPPIKVTSRWTFRCPGCPQALSHDDSHF An isolated chimeric polypeptide encoding M79217_PEA_1_P2 comprising a second amino acid sequence that is at least 90% homologous to HERHKC INFFVKVYGYMPLLYTQFRVDSVLFKTRLPHDKTKFKFI and the first and second amino acid sequences are contiguous and in a contiguous order.

  2. Length “n” (wherein n is at least about 10 amino acids long, optionally at least about 20 amino acids long, preferably at least about 30 amino acids long, more preferably at least about 40 amino acids long, most preferably at least about 50 amino acids in length, at least two amino acids comprising KA, starting from any of the following structures: amino acid numbers 807-x to 807, amino acid numbers 808 + ((n-2)-x) (formula An isolated chimeric polypeptide encoding an edge portion of M79217_PEA_1_P2 comprising a polypeptide, wherein the sequence has a sequence terminating at 0) to n-2).

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: membrane. Protein localization is considered to be membrane as the Signalp_hmm software presumes that this protein has a signal anchor region.

  The mutein M79217_PEA_1_P2 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, enumerating other amino acids, and the last column shows SNPs as shown in Table 583) It indicates whether it is known and the presence of a known SNP in the mutein M79217_PEA_1_P2 sequence supports the deduced sequence of this mutein of the invention).

  The glycosylation sites of the mutant protein M79217_PEA_1_P2 compared to the known protein exostocin-like 3 are shown in Table 584 (showing its position on the amino acid sequence in the first column, the second column has a glycosylation site in the mutant protein) The last column indicates whether this position differs on the mutant protein).

  The mutein M79217_PEA_1_P2 is encoded by the following transcript: M79217_PEA_1_T8 (sequences shown at the end of the application). The code portion of transcript M79217_PEA_1_T8 is shown in bold, this code portion starts at position 748 and ends at position 3468. The transcript also has the following SNPs listed in Table 585 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein M79217_PEA_1_P2 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein M79217_PEA_1_P4 according to the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript M79217_PEA_1_T10. An alignment to a known protein (exostocin-like 3) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between M79217_PEA_1_P4 and EXL3_HUMAN 1. At least 70%, optionally at least 80%, preferably at least 85%, preferably at least 90%, more preferably at least 90%, most preferably at least 95% homologous to the polypeptide having the sequence PELRQPARLGPECWDYRHEPRCPAQMGSHFIVQAGLKLLASSKP PKCWDY corresponding to amino acids 1 to 51 of M79217_PEA_1_P4 1 and the amino acid sequence of EXL3_HUMAN corresponding to amino acids 759 to 919 and to M79217_PEA_1_P4 corresponding to amino acids 52 to 212. RCPGCPQALSHDDSHFHERHKCINFFVKVYGYMPLLYTQFRVDSVLFKTRLPHDKTKCFKFI and and at least 90% homologous to a second amino acid sequence, the first amino acid sequence and a second amino acid sequence, contiguous and in sequential order, the isolated chimeric polypeptide coding M79217_PEA_1_P4.

  2. M79217_PEA_1_P4 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence of P79. An isolated polypeptide encoding

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: membrane. Although protein localization is a partial protein, it is considered to be a membrane because both transmembrane domain estimation programs presume that this protein has a transmembrane domain.

  The mutein M79217_PEA_1_P4 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows SNPs as shown in Table 586) It is shown whether it is known and the presence of a known SNP in the mutein M79217_PEA_1_P4 sequence supports the putative sequence of this mutein of the invention).

  The glycosylation sites of the mutant protein M79217_PEA_1_P4 compared to the known protein Exostosin-like 3 are shown in Table 587 (showing its position on the amino acid sequence in the first column, the second column has a glycosylation site in the mutant protein) The last column indicates whether this position differs on the mutant protein).

  The mutein M79217_PEA_1_P4 is encoded by the following transcript: M79217_PEA_1_T10 (sequences shown at the end of the application). The coding part of the transcript M79217_PEA_1_T10 is shown in bold, starting from position 1 and ending at position 637. The transcript also has the following SNPs listed in Table 588 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein M79217_PEA_1_P4 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein M79217_PEA_1_P8 according to the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript M79217_PEA_1_T15. An alignment to a known protein (exostocin-like 3) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between M79217_PEA_1_P8 and EXL3_HUMAN 1. Corresponding to amino acids 1 to 807 of EXL3_HUMAN, corresponding to amino acids 1 to 807 of M79217_PEA_1_P8 MTGYTMLRNGGAGNGGQTCMLRWSNRIRLTWLSFTLFVILVFFPLIAHYYLTTLDEADEAGKRIFGPRVGNELCEVKHVLDLCRIRESVSEELLQLEAKRQELNSEIAKLNLKIEACKKSIENAKQDLLQLKNVISQTEHSYKELMAQNQPKLSLPIRLLPEKDDAGLPPPKATRGCRLHNCFDYSRCPLTSGFPVYVYDSDQFVFGSYLDPLVKQAFQATARANVYVTENADIACLYVILVGEMQEPVVLRPAELEKQLYSLPHWRTDGHNHVIIN SRKSDTQNLLYNVSTGRAMVAQSTFYTVQYRPGFDLVVSPLVHAMSEPNFMEIPPQVPVKRKYLFTFQGEKIESLRSSLQEARSFEEEMEGDPPADYDDRIIATLKAVQDSKLDQVLVEFTCKNQPKPSLPTEWALCGEREDRLELLKLSTFALIITPGDPRLVISSGCATRLFEALEVGAVPVVLGEQVQLPYQDMLQWNEAALVVPKPRVTEVHFLLRSLSDSDLLAMRRQGRFLWETYFSTADSIFNTVLAMIRTRIQIPAAPIREEAAAEIPHRSGKAAGTDPNMADNGDLDLGPVETEPPYASPRYLRNFTLTVTDFYRSWNCAPGP A first amino acid sequence at least 90% homologous to EichieruefuPieichitiPiefudiPibuieruPiesuieikeiefuerujiesujitijiefuaruPiaijijijieijijiesujikeiiefukyueieierujijienubuiPiaruikyuefutibuibuiemuerutiwaiiaruiibuieruemuenuesueruiarueruenujieruPiwaieruenukeibuibuibuibuidaburyuenuesuPikeieruPiesuidieruerudaburyuPidiaijibuiPiaiemubuibuiarutiikeienuesueruenuenuaruefueruPidaburyuenuiaiitiieiaieruesuaidididieieichieruarueichidiiaiemuefujiefuarubuidaburyuaruieiarudiaruaibuijiefuPijiaruwaieichieidaburyudiaipehaQSWLYNSNYSCELSMVLTGAAFFHK, polypeptide at least 70% with a sequence corresponding to VRKSW to amino acid 808-812 of M79217_PEA_1_P8, optionally at least 80%, preferably at least 85%, more Preferably at least 90%, most preferably less An isolated chimeric polypeptide encoding M79217_PEA_1_P8, which comprises a second amino acid sequence both 95% homologous, said first amino acid sequence and the second amino acid sequence being adjacent and in sequential order.

  2. M79217_PEA_1_P8 comprising a polypeptide at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence VRKSW in M79217_PEA_1_P8 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: membrane. Protein localization is considered to be membrane as the Signalp_hmm software presumes that this protein has a signal anchor region.

  The mutein M79217_PEA_1_P8 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, enumerating other amino acids, and the last column shows SNPs as shown in Table 589) It indicates whether it is known and the presence of a known SNP in the mutein M79217_PEA_1_P8 sequence supports the deduced sequence of this mutein of the invention).

  The glycosylation sites of the mutant protein M79217_PEA_1_P8 compared to the known protein exostocin-like 3 are shown in Table 590 (showing its position on the amino acid sequence in the first column, the second column has glycosylation sites in the mutant protein) The last column indicates whether this position differs on the mutant protein).

  The mutein M79217_PEA_1_P8 is encoded by the following transcript: M79217_PEA_1_T15 (sequences shown at the end of the application). The code portion of transcript M79217_PEA_1_T15 is shown in bold, this code portion starting at position 748 and ending at position 3183. The transcript also has the following SNPs listed in Table 591 (indicating its position on the nucleotide sequence and listing another nucleic acid, the last column indicating whether the SNP is known, mutein M79217_PEA_1_P8 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein M79217_PEA_1_P11 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript M79217_PEA_1_T18. The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is considered to be secreted as it is presumed that this protein has a signal peptide by one of two signal peptide estimation programs (HMM: Signal peptide, NN: NO).

  The mutein M79217_PEA_1_P11 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, enumerating other amino acids, and the last column shows SNPs as shown in Table 592) It is shown whether it is known and the presence of a known SNP in the mutein M79217_PEA_1_P11 sequence supports the putative sequence of this mutein of the invention).

  The mutein M79217_PEA_1_P11 is encoded by the following transcript: M79217_PEA_1_T18 (sequences shown at the end of the application). The code portion of the transcript M79217_PEA_1_T18 is shown in bold, starting from position 1354 and ending at position 1674. The transcript also has the following SNPs listed in Table 593 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein M79217_PEA_1_P11 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  As mentioned above, cluster M79217 is characterized by the 32 segments listed in Table 2 above, the sequence of which is shown at the end of the application. These segments are part of the nucleic acid sequence, which are of particular interest and are individually described herein. A description of each segment of the invention is provided herein.

  The segment cluster M79217_PEA_1_node_2 of the present invention is supported by two libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: M79217_PEA_1_T3. Table 594 below describes the start and end positions of this segment on each transcript.

  The segment cluster M79217_PEA_1_node_4 of the present invention is supported by eight libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: M79217_PEA_1_T8, M79217_PEA_1_T15, and M79217_PEA_1_T18. Table 595 below describes the start and end positions of this segment on each transcript.

  The segment cluster M79217_PEA_1_node_9 of the present invention is supported by two libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: M79217_PEA_1_T1. Table 596 below describes the start and end positions of this segment on each transcript.

  The segment cluster M79217_PEA_1_node_10 of the present invention is supported by 33 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M79217_PEA_1_T1, M79217_PEA_1_T3, M79217_PEA_1_T8, M79217_PEA_1_T15, and M79217_PEA_1_T18. Table 597 below describes the start and end positions of this segment on each transcript.

  Microarray (chip) data for this segment is also available, as follows. As described above, with respect to the clusters themselves, different oligonucleotides were tested for differential expression in different disease states, in particular cancer. The following oligonucleotides were found to reach this segment (for lung cancer) as shown in Table 598.

  The segment cluster M79217_PEA_1_node_11 of the present invention is supported by 42 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M79217_PEA_1_T1, M79217_PEA_1_T3, M79217_PEA_1_T8, and M79217_PEA_1_T15. Table 599 below describes the start and end positions of this segment on each transcript.

  The segment cluster M79217_PEA_1_node_13 of the present invention is supported by 35 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M79217_PEA_1_T1, M79217_PEA_1_T3, M79217_PEA_1_T8, and M79217_PEA_1_T15. Table 600 below lists the start and end positions of this segment on each transcript.

  The segment cluster M79217_PEA_1_node_14 of the present invention is supported by 65 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M79217_PEA_1_T1, M79217_PEA_1_T3, M79217_PEA_1_T8, and M79217_PEA_1_T15. Table 601 below describes the start and end positions of this segment on each transcript.

  The segment cluster M79217_PEA_1_node_16 of the present invention is supported by 51 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M79217_PEA_1_T1, M79217_PEA_1_T3, M79217_PEA_1_T8, and M79217_PEA_1_T15. Table 602 below describes the start and end positions of this segment on each transcript.

  The segment cluster M79217_PEA_1_node_23 of the present invention is supported by 50 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M79217_PEA_1_T1, M79217_PEA_1_T3, M79217_PEA_1_T8, M79217_PEA_1_T10, and M79217_PEA_1_T15. Table 603 below describes the start and end positions of this segment on each transcript.

  The segment cluster M79217_PEA_1_node_24 of the present invention is supported by two libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: M79217_PEA_1_T15. Table 604 below describes the start and end positions of this segment on each transcript.

  The segment cluster M79217_PEA_1_node_31 of the present invention is supported by 50 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M79217_PEA_1_T1, M79217_PEA_1_T3, M79217_PEA_1_T8, and M79217_PEA_1_T10. Table 605 below describes the start and end positions of this segment on each transcript.

  The segment cluster M79217_PEA_1_node_33 of the present invention is supported by 71 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M79217_PEA_1_T1, M79217_PEA_1_T3, M79217_PEA_1_T8, and M79217_PEA_1_T10. Table 606 below describes the start and end positions of this segment on each transcript.

  The segment cluster M79217_PEA_1_node_34 of the present invention is supported by 51 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M79217_PEA_1_T1, M79217_PEA_1_T3, M79217_PEA_1_T8, and M79217_PEA_1_T10. Table 607 below describes the start and end positions of this segment on each transcript.

  The segment cluster M79217_PEA_1_node_35 of the present invention is supported by 53 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M79217_PEA_1_T1, M79217_PEA_1_T3, M79217_PEA_1_T8, and M79217_PEA_1_T10. Table 608 below describes the start and end positions of this segment on each transcript.

  The segment cluster M79217_PEA_1_node_37 of the present invention is supported by 58 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M79217_PEA_1_T1, M79217_PEA_1_T3, M79217_PEA_1_T8, and M79217_PEA_1_T10. Table 609 below describes the start and end positions of this segment on each transcript.

  The segment cluster M79217_PEA_1_node_38 of the present invention is supported by 62 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M79217_PEA_1_T1, M79217_PEA_1_T3, M79217_PEA_1_T8, and M79217_PEA_1_T10. Table 610 below describes the start and end positions of this segment on each transcript.

  The segment cluster M79217_PEA_1_node_41 of the present invention is supported by 171 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M79217_PEA_1_T1, M79217_PEA_1_T3, M79217_PEA_1_T8, M79217_PEA_1_T10, and M79217_PEA_1_T18. Table 611 below describes the start and end positions of this segment on each transcript.

  The segment cluster M79217_PEA_1_node_44 of the present invention is supported by 89 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M79217_PEA_1_T1, M79217_PEA_1_T3, M79217_PEA_1_T8, M79217_PEA_1_T10, and M79217_PEA_1_T18. Table 612 below describes the start and end positions of this segment on each transcript.

  According to an optional embodiment of the present invention, there is also provided a short segment associated with the above cluster. These segments are up to about 120 bp in length and are therefore included in the individual descriptions.

  The segment cluster M79217_PEA_1_node_0 of the present invention is supported by 4 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: M79217_PEA_1_T3. Table 613 below describes the start and end positions of this segment on each transcript.

  The segment cluster M79217_PEA_1_node_7 of the present invention is supported by 11 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M79217_PEA_1_T3, M79217_PEA_1_T8, M79217_PEA_1_T15, and M79217_PEA_1_T18. Table 614 below describes the start and end positions of this segment on each transcript.

  The segment cluster M79217_PEA_1_node_12 according to the invention can be found in the following transcripts: M79217_PEA_1_T1, M79217_PEA_1_T3, M79217_PEA_1_T8, and M79217_PEA_1_T15. Table 615 below describes the start and end positions of this segment on each transcript.

  The segment cluster M79217_PEA_1_node_19 of the present invention is supported by one library. The number of libraries was determined as described above. This segment can be found in the following transcript: M79217_PEA_1_T10. Table 616 below describes the start and end positions of this segment on each transcript.

  The segment cluster M79217_PEA_1_node_21 of the present invention is supported by one library. The number of libraries was determined as described above. This segment can be found in the following transcript: M79217_PEA_1_T10. Table 617 below describes the start and end position of this segment on each transcript.

  The segment cluster M79217_PEA_1_node_26 of the present invention is supported by 40 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M79217_PEA_1_T1, M79217_PEA_1_T3, and M79217_PEA_1_T10. Table 618 below describes the start and end positions of this segment on each transcript.

  The segment cluster M79217_PEA_1_node_27 of the present invention is supported by 46 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M79217_PEA_1_T1, M79217_PEA_1_T3, M79217_PEA_1_T8, and M79217_PEA_1_T10. Table 619 below describes the start and end positions of this segment on each transcript.

  The segment cluster M79217_PEA_1_node_30 of the present invention is supported by 47 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M79217_PEA_1_T1, M79217_PEA_1_T3, M79217_PEA_1_T8, and M79217_PEA_1_T10. Table 620 below describes the start and end positions of this segment on each transcript.

  The segment cluster M79217_PEA_1_node_32 of the present invention is supported by 40 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M79217_PEA_1_T1, M79217_PEA_1_T3, M79217_PEA_1_T8, and M79217_PEA_1_T10. Table 621 below describes the start and end positions of this segment on each transcript.

  The segment cluster M79217_PEA_1_node_36 of the present invention is supported by 42 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M79217_PEA_1_T1, M79217_PEA_1_T3, M79217_PEA_1_T8, and M79217_PEA_1_T10. Table 622 below describes the start and end positions of this segment on each transcript.

  The segment cluster M79217_PEA_1_node_39 of the present invention is supported by 57 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M79217_PEA_1_T1, M79217_PEA_1_T3, M79217_PEA_1_T8, and M79217_PEA_1_T10. Table 623 below describes the start and end positions of this segment on each transcript.

  The segment cluster M79217_PEA_1_node_40 of the present invention is supported by 59 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M79217_PEA_1_T1, M79217_PEA_1_T3, M79217_PEA_1_T8, and M79217_PEA_1_T10. Table 624 below describes the start and end positions of this segment on each transcript.

  The segment cluster M79217_PEA_1_node_42 of the present invention is supported by 99 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M79217_PEA_1_T1, M79217_PEA_1_T3, M79217_PEA_1_T8, M79217_PEA_1_T10, and M79217_PEA_1_T18. Table 625 below describes the start and end position of this segment on each transcript.

  The segment cluster M79217_PEA_1_node_43 of the present invention is supported by 90 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M79217_PEA_1_T1, M79217_PEA_1_T3, M79217_PEA_1_T8, M79217_PEA_1_T10, and M79217_PEA_1_T18. Table 626 below describes the start and end positions of this segment on each transcript.

Mutated protein alignment against previously known proteins:
Sequence name: BAA25445

Sequence documentation:

Alignment of: M79217_PEA_1_P1 x BAA25445 ..

Alignment segment 1/1:

Quality: 9101.00 Escore: 0
Matching length: 919 Total length: 919
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MTGYTMLRNGGAGNGGQTCMLRWSNRIRLTWLSFTLFVILVFFPLIAHYY 50
||||||||||||||||||||||||||||||||||||||||
13 MTGYTMLRNGGAGNGGQTCMLRWSNRIRLTWLSFTLFVILVFFPLIAHYY 62
....
51 LTTLDEADEAGKRIFGPRVGNELCEVKHVLDLCRIRESVSEELLQLEAKR 100
||||||||||||||||||||||||||||||||||||||||
63 LTTLDEADEAGKRIFGPRGNELCEVKHLVLDLRIRESVSEELLQLEAKR 112
....
101 QELNSEIAKLNLKIEACKKSIENAKQDLLQLKNVISQTEHSYKELMAQNQ 150
||||||||||||||||||||||||||||||||||||||||
113 QELNSEIAKLNLKIEACKKSIENAKQDLLQLKNVISQTEHSYKELMAQNQ 162
....
151 PKLSLPIRLLPE KDDAGLPPP KATRGCRLHNCFDYSRCPLTSGFPVYVYD 200
||||||||||||||||||||||||||||||||||||||||
163 PKLSLPIRLLPE KDDAGLPPP KATRGCRLHNCFDYSRCPLTSGFPVYVYD 212
....
201 SDQFVFGSYLDPLVKQAFQATARANVYVTENADIACLYVILVGEMQEPV 250
||||||||||||||||||||||||||||||||||||||||
213 SDQFVFGSYLDPLVKQAFQATARANVYVTENADIACLYVILVGEMQEPV 262
....
251 LRPAELEKQLYSLPHWRTDGHNHVIINLSRKSDTQNLLYNVSTGRAMVAQ 300
||||||||||||||||||||||||||||||||||||||||
263 LRPAELEKQLYSLPHWRTDGHNHVIINLSRKSDTQNLLYNVSTGRAMVAQ 312
....
301 STFYTVQYRPGGFDLVVSPLVHAMSEPNFMEIPPQVPVCRKYLFTFQGEKI 350
||||||||||||||||||||||||||||||||||||||||
313 STFYTVQYRPGGFDLVVSPLVHAMSEPNFMEIPPQVPVCRKYLFTFQGEKI 362
....
351 ESLRSSLQEARSFEEEMEGDPPADDIDRIIATLKAVQDSKLDQVLVEFTC 400
||||||||||||||||||||||||||||||||||||||||
363 ESLRSSLQEARSFEEEMEGDPPADDIDRIIATLKAV QDSKLDQVLVEFTC 412
....
401 KNQPGPSLPTEWALCGEREDRLELL STTFAL II TPG PDRL VISSG CATR 450
||||||||||||||||||||||||||||||||||||||||
413 KNQPFPSLPTEWALCGEREDRLELL KSTFAL II TPGPR L VIS SG CAT R 462
....
451 LFEALEVGAVPPVVLGEQVQLPYQDMLQWNEAALVVPKPRVTEVHFLLRSL 500
||||||||||||||||||||||||||||||||||||||||
463 LFEALVEGVPPV VLGEQVQLPYQDMLQWNEAALVVPKPRFTEVHFLLRSL 512
....
501 SDSDLLAMRRQGRFLWETYFSTADSIFNTVLAMIRTRIQIPAAPIREEAA 550
||||||||||||||||||||||||||||||||||||||||
513 SDSDLLAMRRQGRFLWETYFSTADSIFNTVLAMIRTRIQIPAAPIREEAA 562
....
551 AEIPHRSGKAAGTDPDNMADGNDLDLGPVETEPPYASPRYLRNFTLTVTDF 600
||||||||||||||||||||||||||||||||||||||||
563 AEIPHRSGKAAGTDPDNMADGNDLDLGPVETEPPYASPRYLRNFTLTVTDF 612
....
601 YRSWNCAPGPFHLFPHTPFDPVLPSEAKFLGSGTGFRPIGGGAGGGSGKEF 650
||||||||||||||||||||||||||||||||||||||||
613 YRSWNCAPGPFHLFPHTPFDPVLPSEAKFLGSGTGFRPIGGGAGGGSGKEF 662
....
651 QAALGGNVPREQFTVVMLTYEREEVLMSNLERLNGLPYLNKVVVVWNSPK 700
||||||||||||||||||||||||||||||||||||||||
663 QAALGGNVPREQFTVVMLTYEREEVLMSNLERLNGLPYLNKVVVVWNSPK 712
....
701 LPSEDLLWPDIGVPIMV VRTEK NSLN NRFLPNEIETEAILSDDDAHLR 750
||||||||||||||||||||||||||||||||||||||||
713 LPSEDLLWPDIGVPIMV VRTEK NSLNNLFLPNEIETEAILSDDDAHLR 762
....
751 HDEIMFGFFRWREARDRIVGFPGRYHAWDIPHQSWLYNSNYSCELSMVLT 800
||||||||||||||||||||||||||||||||||||||||
763 HDEIMFGFFRWREARDRIVGFPGRYHAWDIPHQSWLYNSNYSCELSMVLT 812
....
801 GAAFFHKYYAYLYSYVMPQAIRDMVDEYINCEDIAMLFLSHITRKPPIK 850
||||||||||||||||||||||||||||||||||||||||
813 GAAFFHKYYAYLYSYVMPQAIRDMVDEYINCEDIAMLFLSHITRKPPIK 862
....
851 VTSRWTFRCPGCPQALSHDDSHFHERHKCINFFVKVYGYMPLLYTQFRVD 900
||||||||||||||||||||||||||||||||||||||||
863 VTSRWTFRCPGCPQALSHDDSHFHERHKCINFFVKVYGYMPLLYTQFRVD 912
.
901 SVLFKTRLPHDKTKCFKFI 919
||||||||||||||||||
913 SVLFKTRLPHDKTKCFK 931






Sequence name: EXL3_HUMAN

Sequence documentation:

Alignment of: M79217_PEA_1_P2 x EXL3_HUMAN ..

Alignment segment 1/1:

Quality: 8873.00 Escore: 0
Matching length: 907 Total length: 919
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 98.69 Total Percent Identity: 98.69
Gaps: 1

Alignment:
....
1 MTGYTMLRNGGAGNGGQTCMLRWSNRIRLTWLSFTLFVILVFFPLIAHYY 50
||||||||||||||||||||||||||||||||||||||||
1 MTGYTMLRNGGAGNGGQTCMLRWSNRIRLTWLSFTLFVILVFFPLIAHYY 50
....
51 LTTLDEADEAGKRIFGPRVGNELCEVKHVLDLCRIRESVSEELLQLEAKR 100
||||||||||||||||||||||||||||||||||||||||
51 LTTLDEADEAGKRIFGPRVGNELCEVKHVLDLCRIRESVSEELLQLEAKR 100
....
101 QELNSEIAKLNLKIEACKKSIENAKQDLLQLKNVISQTEHSYKELMAQNQ 150
||||||||||||||||||||||||||||||||||||||||
101 QELNSEIAKLNLKIEACKKSIENAKQDLLQLKNVISQTEHSYKELMAQNQ 150
....
151 PKLSLPIRLLPE KDDAGLPPP KATRGCRLHNCFDYSRCPLTSGFPVYVYD 200
||||||||||||||||||||||||||||||||||||||||
151 PKLSLPIRLLPE KDDAGLPPP KATRGCRLHNCFDYSRCPLTSGFPVYVYD 200
....
201 SDQFVFGSYLDPLVKQAFQATARANVYVTENADIACLYVILVGEMQEPV 250
||||||||||||||||||||||||||||||||||||||||
201 SDQFVFGSYLDPLVKQAFQATARANVYVTENADIACLYVILVGEMQEPV 250
....
251 LRPAELEKQLYSLPHWRTDGHNHVIINLSRKSDTQNLLYNVSTGRAMVAQ 300
||||||||||||||||||||||||||||||||||||||||
251 LRPAELEKQLYSLPHWRTDGHNHVIINLSRKSDTQNLLYNVSTGRAMVAQ 300
....
301 STFYTVQYRPGGFDLVVSPLVHAMSEPNFMEIPPQVPVCRKYLFTFQGEKI 350
||||||||||||||||||||||||||||||||||||||||
301 STFYTVQYRPGGFDLVVSPLVHAMSEPNFMEIPPQVPVCRKYLFTFQGEKI 350
....
351 ESLRSSLQEARSFEEEMEGDPPADDIDRIIATLKAVQDSKLDQVLVEFTC 400
||||||||||||||||||||||||||||||||||||||||
351 ESLRSSLQEARSFEEEMEGDPPADDIDRIIATLKAVQDSKLDQVLVEFTC 400
....
401 KNQPGPSLPTEWALCGEREDRLELL STTFAL II TPG PDRL VISSG CATR 450
||||||||||||||||||||||||||||||||||||||||
401 KNQPGPSLPTEWALCGEREDRLELL STTFAL II TPG PDRL VISSG CATR 450
....
451 LFEALEVGAVPPVVLGEQVQLPYQDMLQWNEAALVVPKPRVTEVHFLLRSL 500
||||||||||||||||||||||||||||||||||||||||
451 LFEALEVGAVPPVVLGEQVQLPYQDMLQWNEAALVVPKPRVTEVHFLLRSL 500
....
501 SDSDLLAMRRQGRFLWETYFSTADSIFNTVLAMIRTRIQIPAAPIREEAA 550
||||||||||||||||||||||||||||||||||||||||
501 SDSDLLAMRRQGRFLWETYFSTADSIFNTVLAMIRTRIQIPAAPIREEAA 550
....
551 AEIPHRSGKAAGTDPDNMADGNDLDLGPVETEPPYASPRYLRNFTLTVTDF 600
||||||||||||||||||||||||||||||||||||||||
551 AEIPHRSGKAAGTDPDNMADGNDLDLGPVETEPPYASPRYLRNFTLTVTDF 600
....
601 YRSWNCAPGPFHLFPHTPFDPVLPSEAKFLGSGTGFRPIGGGAGGGSGKEF 650
||||||||||||||||||||||||||||||||||||||||
601 YRSWNCAPGPFHLFPHTPFDPVLPSEAKFLGSGTGFRPIGGGAGGGSGKEF 650
....
651 QAALGGNVPREQFTVVMLTYEREEVLMSNLERLNGLPYLNKVVVVWNSPK 700
||||||||||||||||||||||||||||||||||||||||
651 QAALGGNVPREQFTVVMLTYEREEVLMSNLERLNGLPYLNKVVVVWNSPK 700
....
701 LPSEDLLWPDIGVPIMV VRTEK NSLN NRFLPNEIETEAILSDDDAHLR 750
||||||||||||||||||||||||||||||||||||||||
701 LPSEDLLWPDIGVPIMV VRTEK NSLN NRFLPNEIETEAILSDDDAHLR 750
....
751 HDEIMFGFFRWREARDRIVGFPGRYHAWDIPHQSWLYNSNYSCELSMVLT 800
||||||||||||||||||||||||||||||||||||||||
751 HDEIMFGFFRWREARDRIVGFPGRYHAWDIPHQSWLYNSNYSCELSMVLT 800
....
801 GAAFFHK ............ AIRDMVDEYINCEDIAMNFLVSHITRKPPIK 838
||||||||||||||||||||||||||||||||||
801 GAAFFHKYYAYLYSYVMPQAIRDMVDEYINCEDIAMLFLSHITRKPPIK 850
....
839 VTSRWTFRCPGCPQALSHDDSHFHERHKCINFFVKVYGYMPLLYTQFRVD 888
||||||||||||||||||||||||||||||||||||||||
851 VTSRWTFRCPGCPQALSHDDSHFHERHKCINFFVKVYGYMPLLYTQFRVD 900
.
889 SVLFKTRLPHDKTKCFK 907
||||||||||||||||||
901 SVLFKTRLPHDKTKCFKFI 919






Sequence name: EXL3_HUMAN

Sequence documentation:

Alignment of: M79217_PEA_1_P4 x EXL3_HUMAN ..

Alignment segment 1/1:

Quality: 1668.00 Escore: 0
Matching length: 162 Total length: 162
Matching Percent Similarity: 100.00 Matching Percent Identity: 99.38
Total Percent Similarity: 100.00 Total Percent Identity: 99.38
Gaps: 0

Alignment:
....
51 YRVWREARDRIVGFPGRYHAWDIPHQSWLYNSNYSCELSMVLTGAAFFHK 100
: ||||||||||||||||||||||||||||||||||||||||
758 FRVWREARDRIVGFPGRYHAWDIPHQSWLYNSNYSCELSMVLTGAAFFHK 807
....
101 YYALYSYVMPQAIRDMVDEYINCEDIAMLFLSHITRKPPIKVTSRWTF 150
||||||||||||||||||||||||||||||||||||||||
808 YAYLYSYVMPQAIRDMVDEYINCEDIAMLFLSHITRKPPIKVTSRWTF 857
....
151 RCPGCPQALSHDDSHFHERHKCINFFVKVYGYMPLLYTQFRVDSVLFKTR 200
||||||||||||||||||||||||||||||||||||||||
858 RCPGCPQALSHDDSHFHERHKCINFFVKVYGYMPLLYTQFRVDSVLFKTR 907
.
201 LPHDKTKCFKFI 212
||||||||||||
908 LPHDKTKCFKFI 919






Sequence name: EXL3_HUMAN

Sequence documentation:

Alignment of: M79217_PEA_1_P8 x EXL3_HUMAN ..

Alignment segment 1/1:

Quality: 7947.00 Escore: 0
Matching length: 807 Total length: 807
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MTGYTMLRNGGAGNGGQTCMLRWSNRIRLTWLSFTLFVILVFFPLIAHYY 50
||||||||||||||||||||||||||||||||||||||||
1 MTGYTMLRNGGAGNGGQTCMLRWSNRIRLTWLSFTLFVILVFFPLIAHYY 50
....
51 LTTLDEADEAGKRIFGPRVGNELCEVKHVLDLCRIRESVSEELLQLEAKR 100
||||||||||||||||||||||||||||||||||||||||
51 LTTLDEADEAGKRIFGPRVGNELCEVKHVLDLCRIRESVSEELLQLEAKR 100
....
101 QELNSEIAKLNLKIEACKKSIENAKQDLLQLKNVISQTEHSYKELMAQNQ 150
||||||||||||||||||||||||||||||||||||||||
101 QELNSEIAKLNLKIEACKKSIENAKQDLLQLKNVISQTEHSYKELMAQNQ 150
....
151 PKLSLPIRLLPE KDDAGLPPP KATRGCRLHNCFDYSRCPLTSGFPVYVYD 200
||||||||||||||||||||||||||||||||||||||||
151 PKLSLPIRLLPE KDDAGLPPP KATRGCRLHNCFDYSRCPLTSGFPVYVYD 200
....
201 SDQFVFGSYLDPLVKQAFQATARANVYVTENADIACLYVILVGEMQEPV 250
||||||||||||||||||||||||||||||||||||||||
201 SDQFVFGSYLDPLVKQAFQATARANVYVTENADIACLYVILVGEMQEPV 250
....
251 LRPAELEKQLYSLPHWRTDGHNHVIINLSRKSDTQNLLYNVSTGRAMVAQ 300
||||||||||||||||||||||||||||||||||||||||
251 LRPAELEKQLYSLPHWRTDGHNHVIINLSRKSDTQNLLYNVSTGRAMVAQ 300
....
301 STFYTVQYRPGGFDLVVSPLVHAMSEPNFMEIPPQVPVCRKYLFTFQGEKI 350
||||||||||||||||||||||||||||||||||||||||
301 STFYTVQYRPGGFDLVVSPLVHAMSEPNFMEIPPQVPVCRKYLFTFQGEKI 350
....
351 ESLRSSLQEARSFEEEMEGDPPADDIDRIIATLKAVQDSKLDQVLVEFTC 400
||||||||||||||||||||||||||||||||||||||||
351 ESLRSSLQEARSFEEEMEGDPPADDIDRIIATLKAVQDSKLDQVLVEFTC 400
....
401 KNQPGPSLPTEWALCGEREDRLELL STTFAL II TPG PDRL VISSG CATR 450
||||||||||||||||||||||||||||||||||||||||
401 KNQPGPSLPTEWALCGEREDRLELL STTFAL II TPG PDRL VISSG CATR 450
....
451 LFEALEVGAVPPVVLGEQVQLPYQDMLQWNEAALVVPKPRVTEVHFLLRSL 500
||||||||||||||||||||||||||||||||||||||||
451 LFEALEVGAVPPVVLGEQVQLPYQDMLQWNEAALVVPKPRVTEVHFLLRSL 500
....
501 SDSDLLAMRRQGRFLWETYFSTADSIFNTVLAMIRTRIQIPAAPIREEAA 550
||||||||||||||||||||||||||||||||||||||||
501 SDSDLLAMRRQGRFLWETYFSTADSIFNTVLAMIRTRIQIPAAPIREEAA 550
....
551 AEIPHRSGKAAGTDPDNMADGNDLDLGPVETEPPYASPRYLRNFTLTVTDF 600
||||||||||||||||||||||||||||||||||||||||
551 AEIPHRSGKAAGTDPDNMADGNDLDLGPVETEPPYASPRYLRNFTLTVTDF 600
....
601 YRSWNCAPGPFHLFPHTPFDPVLPSEAKFLGSGTGFRPIGGGAGGGSGKEF 650
||||||||||||||||||||||||||||||||||||||||
601 YRSWNCAPGPFHLFPHTPFDPVLPSEAKFLGSGTGFRPIGGGAGGGSGKEF 650
....
651 QAALGGNVPREQFTVVMLTYEREEVLMSNLERLNGLPYLNKVVVVWNSPK 700
||||||||||||||||||||||||||||||||||||||||
651 QAALGGNVPREQFTVVMLTYEREEVLMSNLERLNGLPYLNKVVVVWNSPK 700
....
701 LPSEDLLWPDIGVPIMV VRTEK NSLN NRFLPNEIETEAILSDDDAHLR 750
||||||||||||||||||||||||||||||||||||||||
701 LPSEDLLWPDIGVPIMV VRTEK NSLN NRFLPNEIETEAILSDDDAHLR 750
....
751 HDEIMFGFFRWREARDRIVGFPGRYHAWDIPHQSWLYNSNYSCELSMVLT 800
||||||||||||||||||||||||||||||||||||||||
751 HDEIMFGFFRWREARDRIVGFPGRYHAWDIPHQSWLYNSNYSCELSMVLT 800

801 GAAFFHK 807
||||||||
801 GAAFFHK 807

Description of cluster M62096 Cluster M62096 is characterized by 9 transcripts and 42 segments of interest, the names of which are shown in Tables 627 and 628, respectively, and the sequence itself is shown at the end of the application. Selected protein variants are shown in Table 629.

  These sequences are also known as kinesin heavy chain isoform 5C (SwissProt accession identifier KF5C_HUMAN), a known protein known previously as a protein previously known herein, the synonym kinesin heavy chain neuron specific 2 ) (SEQ ID NO: 1438).

  The protein kinesin heavy chain isoform 5C is known or considered to have the following function: Kinesin is a micro-promoting bond protein that can play a role in organelle transport . The sequence of the protein kinesin heavy chain isoform 5C is shown at the end of the application as "kinesin heavy chain isoform 5C amino acid sequence". Known polymorphisms of this sequence are shown in Table 630.

  The following GO annotation applies to previously known proteins. The following annotations were found: organization of organelles that are relevant to biological processes, and biosynthesis, microtubule motors that are annotations that are relevant to molecular function, ATP binding, and cellular components. Kinesin is a related annotation.

  GO assignments can be made at one or more http: // www. expasy. SwissProt / TremBl Protein knowledgebase available from ch / sprot / or http: // www. ncbi. nlm. nih. Depends on Locuslink available from gov / projects / LocusLink /.

  As mentioned above, cluster M62096 is characterized by the nine transcripts listed in Table 1 above. These transcripts encode a protein that is a variant of the protein kinesin heavy chain isoform 5C. A description of each mutein of the invention is provided herein.

  The mutein M62096_PEA_1_P4 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript M62096_PEA_1_T6. An alignment to a known protein (kinesin heavy chain isoform 5C) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report on comparison between M62096_PEA_1_P4 and KF5C_HUMAN 1. A polypeptide having at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homology to a polypeptide having the sequence MATYIH corresponding to amino acids 1 to 6 of M62096_PEA_1_P4 The amino acid sequence of 1 and the amino acid 239 to 957 of KF5C_HUMAN and the amino acid 7 to 725 of M62096_PEA_1_P4 correspond to VSKTGAEGAVLDEAKNINKSLSALGGNVISALAEGTKTKVPYRDSKMTRTICCTS VFNG ETCSTGIFGTGAKTIKNTVSVNLELTAETECECL KDQKNLEPCDNTPIIDNIAPVVAGISTEEKEKYDEEISSLYRQLDDKDDEINQQSQLAEKLKQQMLDQDELLASTRRDYEKIQEELTRLQIENEAAKDEVKEVLQALEELAVNYDQKSQEVEDKTRANEQLTDELAQKTTTLTTTQRELSQLQELSNHQKKRATEILNLLLKDLGEIGGIIGTNDVKTLADVNGVIEEEFTMARLYISKMKSEVKSLVNRSKQLESAQMDSNRKMNASERELAACQLLISQHEAKIKSLTDYMQNMEQKRRQLEESQDSLSEELAKLRAQEKMHEVSFQDKEKEHLTRLQDAEEMKKALEQQMESHREAHQK LSRLRDEIEEKQKIIDEIRDLNQKLQLEQEKLSSDYNKLKIEDQEREMKLEKLLLLNDKREQAREDLKGLEETVSRELQTLHNLRKLFVQDLTTRVKKSVELDNDDGGGSAAQKQKISFLENNLEQLTKVHKQLVRDNADLRCELPKLEKRLRATAERVKALESALKEAKENAMRDRKRYQQEVDRIKEAVRAKNMARRAHSAQIAKPIRPGHYPASSPTAVHAIRGGGGSSSNSTHYQK and and at least 90% homologous to a second amino acid sequence, the first amino acid sequence and a second amino acid sequence, contiguous and in sequential order, isolated chimera encoding M62096_PEA_1_P4 Polypeptide.

  2. The tip of M62096_PEA_1_P4 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence MATYIH of M62096_PEA_1_P4 An isolated polypeptide encoding

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: Intracellular. Protein localization is considered to be intracellular as no transmembrane domain estimation program will deduce that this protein is a transmembrane domain. Furthermore, both signal peptide deducing programs deduce that this protein is a non-secretory protein.

  The mutein M62096_PEA_1_P4 is encoded by the following transcript: M62096_PEA_1_T6 (sequences shown at the end of the application). The coding part of the transcript M62096_PEA_1_T6 is shown in bold, starting from position 108 and ending at position 2282. The transcript also has the following SNPs listed in Table 631 (indicating its position on the nucleotide sequence and listing another nucleic acid, the last column indicates whether the SNP is known, mutein M62096_PEA_1_P4 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein M62096_PEA_1_P5 according to the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript M62096_PEA_1_T7. An alignment to a known protein (kinesin heavy chain isoform 5C) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report on comparison between M62096_PEA_1_P5 and KF5C_HUMAN 1. Corresponding to amino acids 284-957 of KF5C_HUMAN, corresponding to amino acids 1 to 674 of M62096_PEA_1_P5 MTRILQDSLGGNCRTTIVICCSPSVFNEAETKSTLMFGQRAKTIKNTVSVNLELTAEEWKKKYEKEKEKNKTLKNVIQHLEMELNRWRNGEAVPEDEQISAKDQKNLEPCDNTPIIDNIAPVVAGISTEEKEKYDEEISSLYRQLDDKDDEINQQSQLAEKLKQQMLDQDELLASTRRDYEKIQEELTRLQIENEAAKDEVKEVLQALEELAVNYDQKSQEVEDKTRANEQLTDELAQKTTTLTTTQRELSQLQELSNHQKKRATEILNLLLKDL EIGGIIGTNDVKTLADVNGVIEEEFTMARLYISKMKSEVKSLVNRSKQLESAQMDSNRKMNASERELAACQLLISQHEAKIKSLTDYMQNMEQKRRQLEESQDSLSEELAKLRAQEKMHEVSFQDKEKEHLTRLQDAEEMKKALEQQMESHREAHQKQLSRLRDEIEEKQKIIDEIRDLNQKLQLEQEKLSSDYNKLKIEDQEREMKLEKLLLLNDKREQAREDLKGLEETVSRELQTLHNLRKLFVQDLTTRVKKSVELDNDDGGGSAAQKQKISFLENNLEQLTKVHKQLVRDNADLRCELPKLEKRLRATAERVKALESALKEAKENAM DRKRYQQEVDRIKEAVRAKNMARRAHSAQIAKPIRPGHYPASSPTAVHAIRGGGGSSSNSTHYQK and containing at least 90% homologous first amino acid sequence, isolated chimeric polypeptide coding M62096_PEA_1_P5.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: Intracellular. Protein localization is considered to be intracellular as no transmembrane domain estimation program will deduce that this protein is a transmembrane domain. Furthermore, both signal peptide deducing programs deduce that this protein is a non-secretory protein.

  The mutein M62096_PEA_1_P5 is encoded by the following transcript: M62096_PEA_1_T7 (sequences shown at the end of the application). The coding part of the transcript M62096_PEA_1_T7 is shown in bold, starting from position 283 and ending at position 2304. The transcript also has the following SNPs listed in Table 632 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein M62096_PEA_1_P5 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein M62096_PEA_1_P3 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript M62096_PEA_1_T9. An alignment to a known protein (kinesin heavy chain isoform 5C) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Reporting the comparison between M62096_PEA_1_P3 and KF5C_HUMAN 1. Corresponding to amino acids 365-957 of KF5C_HUMAN, corresponding to amino acids 1 to 593 of M62096_PEA_1_P3 MELNRWRNGEAVPEDEQISAKDQKNLEPCDNTPIIDNIAPVVAGISTEEKEKYDEEISSLYRQLDDKDDEINQQSQLAEKLKQQMLDQDELLASTRRDYEKIQEELTRLQIENEAAKDEVKEVLQALEELAVNYDQKSQEVEDKTRANEQLTDELAQKTTTLTTTQRELSQLQELSNHQKKRATEILNLLLKDLGEIGGIIGTNDVKTLADVNGVIEEEFTMARLYISKMKSEVKSLVNRSKQLESAQMDSNRKMNASERELAACQLLISQHEAK KSLTDYMQNMEQKRRQLEESQDSLSEELAKLRAQEKMHEVSFQDKEKEHLTRLQDAEEMKKALEQQMESHREAHQKQLSRLRDEIEEKQKIIDEIRDLNQKLQLEQEKLSSDYNKLKIEDQEREMKLEKLLLLNDKREQAREDLKGLEETVSRELQTLHNLRKLFVQDLTTRVKKSVELDNDDGGGSAAQKQKISFLENNLEQLTKVHKQLVRDNADLRCELPKLEKRLRATAERVKALESALKEAKENAMRDRKRYQQEVDRIKEAVRAKNMARRAHSAQIAKPIRPGHYPASSPTAVHAIRGGGGSSSNSTHYQK at least 90% homologous first Containing amino acid sequence, isolated chimeric polypeptide coding M62096_PEA_1_P3.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: Intracellular. Protein localization is considered to be intracellular as no transmembrane domain estimation program will deduce that this protein is a transmembrane domain. Furthermore, both signal peptide deducing programs deduce that this protein is a non-secretory protein.

  The mutein M62096_PEA_1_P3 is encoded by the following transcript: M62096_PEA_1_T9 (sequences shown at the end of the application). The coding part of the transcript M62096_PEA_1_T9 is shown in bold, starting from position 565 and ending at position 2343. The transcript also has the following SNPs listed in Table 633 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein M62096_PEA_1_P3 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein M62096_PEA_1_P7 according to the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript M62096_PEA_1_T11. An alignment to a known protein (kinesin heavy chain isoform 5C) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report on comparison between M62096_PEA_1_P7 and KF5C_HUMAN 1. At least 70%, optionally at least 80%, preferably at least 85%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous to a polypeptide having the sequence MTQNFRLMWNILLFPLNFS corresponding to amino acids 1-19 of M62096_PEA_1_P7 1 LNQKLQLEQEKLSDSYNCLKIEDQ EREMM KLEKLLLLLNDKREQAREDLKGLEETVSRELQTLHPLKKKV SVEELDNDDGGGSAAQKQQLQILQL LRATAERVKALESALKEAKENAMRDRKRYQQEVDRIKEAVRAKNMARRAHSAQIAKPIRPGHYPASSPTAVHAIRGGGGSSSNSTHYQK and and at least 90% homologous to a second amino acid sequence, the first amino acid sequence and a second amino acid sequence, contiguous and in sequential order, the isolated chimeric polypeptide coding M62096_PEA_1_P7.

  2. The tip of M62096_PEA_1_P7 comprising a polypeptide that is at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence MTQNFRLMWNILLFPLNFS of M62096_PEA_1_P7 An isolated polypeptide encoding

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is considered to be secreted since it is presumed that this protein has a signal peptide by one of two signal peptide estimation programs (HMM: Non-secretory protein, NN: YES).

  The mutein M62096_PEA_1_P7 is encoded by the following transcript: M62096_PEA_1_T11 (sequences shown at the end of the application). The coding portion of the transcript M62096_PEA_1_T11 is shown in bold, starting from position 633 and ending at position 1349. The transcript also has the following SNPs listed in Table 634 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein M62096_PEA_1_P7 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein M62096_PEA_1_P8 according to the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript M62096_PEA_1_T13. An alignment to a known protein (kinesin heavy chain isoform 5C) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Reporting the comparison between M62096_PEA_1_P8 and KF5C_HUMAN 1. Corresponding to amino acids 1 to 736 of KF5C_HUMAN, corresponding to amino acids 1 to 736 of M62096_PEA_1_P8 MADPAECSIKVMCRFRPLNEAEILRGDKFIPKFKGDETVVIGQGKPYVFDRVLPPNTTQEQVYNACAKQIVKDVLEGYNGTIFAYGQTSSGKTHTMEGKLHDPQLMGIIPRIAHDIFDHIYSMDENLEFHIKVSYFEIYLDKIRDLLDVSKTNLAVHEDKNRVPYVKGCTERFVSSPEEVMDVIDEGKANRHVAVTNMNEHSSRSHSIFLINIKQENVETEKKLSGKLYLVDLAGSEKVSKTGAEGAVLDEAKNINKSLSALGNVISALAEGTKTHV YRDSKMTRILQDSLGGNCRTTIVICCSPSVFNEAETKSTLMFGQRAKTIKNTVSVNLELTAEEWKKKYEKEKEKNKTLKNVIQHLEMELNRWRNGEAVPEDEQISAKDQKNLEPCDNTPIIDNIAPVVAGISTEEKEKYDEEISSLYRQLDDKDDEINQQSQLAEKLKQQMLDQDELLASTRRDYEKIQEELTRLQIENEAAKDEVKEVLQALEELAVNYDQKSQEVEDKTRANEQLTDELAQKTTTLTTTQRELSQLQELSNHQKKRATEILNLLLKDLGEIGGIIGTNDVKTLADVNGVIEEEFTMARLYISKMKSEVKSLVNRSKQLES A first amino acid sequence at least 90% homologous to the first amino acid sequence, and a ura- Is at least 90%, most preferably at least 95% homologous, with a second amino acid sequence, said first amino acid sequence and said second amino acid sequence being adjacent and in sequential order, M62096_PEA_1 An isolated chimeric polypeptide encoding P8.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: Intracellular. Protein localization is considered to be intracellular as no transmembrane domain estimation program will deduce that this protein is a transmembrane domain. Furthermore, both signal peptide deducing programs deduce that this protein is a non-secretory protein.

  The mutein M62096_PEA_1_P8 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, enumerating other amino acids, and the last column shows SNPs as shown in Table 635) It is shown whether it is known and the presence of a known SNP in the mutein M62096_PEA_1_P8 sequence supports the putative sequence of this mutein of the invention).

  The mutein M62096_PEA_1_P8 is encoded by the following transcript: M62096_PEA_1_T13 (sequences shown at the end of the application). The coding part of the transcript M62096_PEA_1_T13 is shown in bold, starting from position 396 and ending at position 2606. The transcript also has the following SNPs listed in Table 636 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein M62096_PEA_1_P8 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein M62096_PEA_1_P9 according to the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript M62096_PEA_1_T14. An alignment to a known protein (kinesin heavy chain isoform 5C) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between M62096_PEA_1_P9 and KF5C_HUMAN Corresponding to amino acids 1 to 454 of KF5C_HUMAN, corresponding to amino acids 1 to 454 of M62096_PEA_1_P9 MADPAECSIKVMCRFRPLNEAEILRGDKFIPKFKGDETVVIGQGKPYVFDRVLPPNTTQEQVYNACAKQIVKDVLEGYNGTIFAYGQTSSGKTHTMEGKLHDPQLMGIIPRIAHDIFDHIYSMDENLEFHIKVSYFEIYLDKIRDLLDVSKTNLAVHEDKNRVPYVKGCTERFVSSPEEVMDVIDEGKANRHVAVTNMNEHSSRSHSIFLINIKQENVETEKKLSGKLYLVDLAGSEKVSKTGAEGAVLDEAKNINKSLSALGNVISALAEGTKTHV The first amino acid sequence at least 90% homologous to WaiarudiesukeiemutiaruaierukyudiesuerujijienushiarutitiaibuiaishishiesuPiesubuiefuenuieiitikeiesutieruemuefujikyuarueikeitiaikeienutibuiesubuienueruierutieiiidaburyukeikeikeiwaiikeiikeiikeienukeitierukeienubuiaikyueichieruiemuieruenuarudaburyuaruenujiieibuiPiidiikyuaiesueikeidikyukeienueruiPishidienutiPiaiaidienuaieiPibuibuieijiaiesutiiikeiikeiwaidiiiaiesuesueruwaiarukyuerudiDKDDEINQQSQLAEKLKQQMLDQDE, polypeptide at least 70% with a sequence corresponding to VKNAIYFFFHKVLLLLFVVDVCSRNLIGIEAFHNYRIMWKFLGRCPFTASYKLIITEFRK to amino acid 455-514 of M62096_PEA_1_P9, optionally at least 80%, preferably A second amino acid sequence that is at least 85%, more preferably at least 90%, most preferably at least 95% homologous, said first amino acid sequence and the second amino acid sequence being in contiguous and contiguous order An isolated chimeric polypeptide encoding M62096_PEA_1_P9.

  2. A sequence comprising at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous polypeptide in sequence MKK An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: Intracellular. Protein localization is considered to be intracellular as no transmembrane domain estimation program will deduce that this protein is a transmembrane domain. Furthermore, both signal peptide deducing programs deduce that this protein is a non-secretory protein.

  The mutein M62096_PEA_1_P9 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows SNPs as shown in Table 637) It is shown whether it is known and the presence of a known SNP in the mutein M62096_PEA_1_P9 sequence supports the deduced sequence of this mutein of the invention).

  The mutein M62096_PEA_1_P9 is encoded by the following transcript: M62096_PEA_1_T14 (sequences shown at the end of the application). The coding part of the transcript M62096_PEA_1_T14 is shown in bold, starting from position 396 and ending at position 1937. The transcript also has the following SNPs listed in Table 638 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein M62096_PEA_1_P9 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein M62096_PEA_1_P10 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript M62096_PEA_1_T15. An alignment to a known protein (kinesin heavy chain isoform 5C) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Reporting of the comparison between M62096_PEA_1_P10 and KF5C_HUMAN At least 70%, optionally at least 80%, preferably at least 85%, preferably at least 90%, more preferably at least 90%, most preferably at least 95% homologous to a polypeptide having the sequence MTQNFRLMWNILLFPLNFS corresponding to amino acids 1-19 of M62096_PEA_1_P10 LNQKLQLEQEKLSSDYNKLKIEDQ EREMKLEK ELLLLND KREQAREDLKGLEETSRELQTLHNLLFVQDLTTRVKK corresponding to amino acids 738 to 815 of KF5C_HUMAN and corresponding to amino acids 20 to 97 of M62096_PEA_1_P10 The amino acid sequence of amino acids A polypeptide having the corresponding sequence VSSLCLNGTEKKIKDGREESFSVEISLA and comprising a third amino acid sequence which is at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous An isolated chimeric polypeptide encoding M62096_PEA_1_P10, wherein the first amino acid sequence, the second amino acid sequence, and the third amino acid sequence are adjacent and in sequential order.

  2. The tip of M62096_PEA_1_P10 comprising a polypeptide that is at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence MTQNFRLMWNILLFPLNFS of M62096_PEA_1_P10 An isolated polypeptide encoding

  3. M62096_PEA_1_P10 comprising a polypeptide at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence VSSLCLNGTEKKIKDGREESFSVEISLA in An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is considered to be secreted since it is presumed that this protein has a signal peptide by one of two signal peptide estimation programs (HMM: Non-secretory protein, NN: YES).

  The mutein M62096_PEA_1_P10 is encoded by the following transcript: M62096_PEA_1_T15 (sequences shown at the end of the application). The coding part of the transcript M62096_PEA_1_T15 is shown in bold, starting from position 633 and ending at position 1007.

  The mutein M62096_PEA_1_P11 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript M62096_PEA_1_T4. An alignment to a known protein (kinesin heavy chain isoform 5C) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report on comparison between M62096_PEA_1_P11 and KF5C_HUMAN 1. Corresponding to amino acids 1 to 372 of KF5C_HUMAN, corresponding to amino acids 1 to 372 of M62096_PEA_1_P11 MADPAECSIKVMCRFRPLNEAEILRGDKFIPKFKGDETVVIGQGKPYVFDRVLPPNTTQEQVYNACAKQIVKDVLEGYNGTIFAYGQTSSGKTHTMEGKLHDPQLMGIIPRIAHDIFDHIYSMDENLEFHIKVSYFEIYLDKIRDLLDVSKTNLAVHEDKNRVPYVKGCTERFVSSPEEVMDVIDEGKANRHVAVTNMNEHSSRSHSIFLINIKQENVETEKKLSGKLYLVDLAGSEKVSKTGAEGAVLDEAKNINKSLSALGNVISALAEGTKTH PYRSKSMTRILQDSLGGNCRTTIVICCS VSFNEAETKSTLMFGQRAKTIKNTVSVNLELTAEEWKKEKEKEKEK NKTLKNVI QH The key amino acid sequence at least 90% homologous to the amino acid 37-385 of M62096_PEA_1_P11 and the peptide having at least 70% Comprises M62096_PEA_1_P11, which comprises a second amino acid sequence which is at least 90%, most preferably at least 95% homologous, said first amino acid sequence and the second amino acid sequence being adjacent and in sequential order Isolated chimera port Peptide.

  2. M62096_PEA_1_P11 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence DFLAAHVFGKLLE in M62096_PEA_1_P11 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: Intracellular. Protein localization is considered to be intracellular as no transmembrane domain estimation program will deduce that this protein is a transmembrane domain. Furthermore, both signal peptide deducing programs deduce that this protein is a non-secretory protein.

  The mutein M62096_PEA_1_P11 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows SNPs as shown in Table 639) It is shown whether it is known and the presence of a known SNP in the mutein M62096_PEA_1_P11 sequence supports the deduced sequence of this mutein of the invention).

  The mutein M62096_PEA_1_P11 is encoded by the following transcript: M62096_PEA_1_T4 (sequences shown at the end of the application). The coding part of the transcript M62096_PEA_1_T4 is shown in bold, starting from position 396 and ending at position 1550. The transcript also has the following SNPs listed in Table 640 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein M62096_PEA_1_P11 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein M62096_PEA_1_P12 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript M62096_PEA_1_T5. An alignment to a known protein (kinesin heavy chain isoform 5C) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Reporting the comparison between M62096_PEA_1_P12 and KF5C_HUMAN Corresponding to amino acids 1 to 323 of KF5C_HUMAN, corresponding to amino acids 1 to 323 of M62096_PEA_1_P12 MADPAECSIKVMCRFRPLNEAEILRGDKFIPKFKGDETVVIGQGKPYVFDRVLPPNTTQEQVYNACAKQIVKDVLEGYNGTIFAYGQTSSGKTHTMEGKLHDPQLMGIIPRIAHDIFDHIYSMDENLEFHIKVSYFEIYLDKIRDLLDVSKTNLAVHEDKNRVPYVKGCTERFVSSPEEVMDVIDEGKANRHVAVTNMNEHSSRSHSIFLINIKQENVETEKKLSGKLYLVDLAGSEKVSKTGAEGAVLDEAKNINKSLSALGNVISALAEGTKTH And a polypeptide having a sequence V corresponding to amino acids 324-324 of M62096_PEA_1_P12 at least 70%, optionally at least 80%, preferably at least 85%, more preferably a first amino acid sequence at least 90% homologous to PYRDSKMTRIQDSLGGNCRTTIVICCS VSFNEAETKSTLMFGQR Comprises M62096_PEA_1_P12, which comprises a second amino acid sequence which is at least 90%, most preferably at least 95% homologous, said first amino acid sequence and the second amino acid sequence being adjacent and in sequential order Isolated chimeric polypeptide.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: Intracellular. Protein localization is considered to be intracellular as no transmembrane domain estimation program will deduce that this protein is a transmembrane domain. Furthermore, both signal peptide deducing programs deduce that this protein is a non-secretory protein.

  The mutein M62096_PEA_1_P12 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, enumerating other amino acids, and the last column shows SNPs as shown in Table 641) It is shown whether it is known and the presence of a known SNP in the mutein M62096_PEA_1_P12 sequence supports the putative sequence of this mutein of the invention).

  The mutein M62096_PEA_1_P12 is encoded by the following transcript: M62096_PEA_1_T5 (sequences shown at the end of the application). The coding part of the transcript M62096_PEA_1_T5 is shown in bold, starting from position 378 and ending at position 1349. The transcript also has the following SNPs listed in Table 642 (showing its position on the nucleotide sequence and listing another nucleic acid, the last column indicating whether the SNP is known, mutein M62096_PEA_1_P12 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  As mentioned above, cluster M62096 is characterized by the 42 segments listed in Table 2 above, the sequence of which is shown at the end of the application. These segments are part of the nucleic acid sequence, which are of particular interest and are individually described herein. A description of each segment of the invention is provided herein.

  The segment cluster M62096_PEA_1_node_0 of the present invention is supported by 14 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: M62096_PEA_1_T4, M62096_PEA_1_T5, M62096_PEA_1_T13, and M62096_PEA_1_T14. Table 643 below describes the start and end positions of this segment on each transcript.

  The segment cluster M62096_PEA_1_node_2 of the present invention is supported by 12 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: M62096_PEA_1_T4, M62096_PEA_1_T5, M62096_PEA_1_T13, and M62096_PEA_1_T14. Table 644 below describes the start and end positions of this segment on each transcript.

  The segment cluster M62096_PEA_1_node_15 of the present invention is supported by 28 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: M62096_PEA_1_T4, M62096_PEA_1_T5, M62096_PEA_1_T13, and M62096_PEA_1_T14. Table 645 below describes the start and end positions of this segment on each transcript.

  The segment cluster M62096_PEA_1_node_17 of the present invention is supported by one library. The number of libraries was determined as described above. This segment can be found in the following transcript: M62096_PEA_1_T7. Table 646 below describes the start and end positions of this segment on each transcript.

  The segment cluster M62096_PEA_1_node_19 of the present invention is supported by three libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: M62096_PEA_1_T6 and M62096_PEA_1_T9. Table 647 below describes the start and end positions of this segment on each transcript.

  The segment cluster M62096_PEA_1_node_23 of the present invention is supported by 36 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M62096_PEA_1_T4, M62096_PEA_1_T5, M62096_PEA_1_T6, M62096_PEA_1_T7, M62096_PEA_1_T9, M62096_PEA_1_T13, and M62096_PEA_1_T14. Table 648 below describes the start and end positions of this segment on each transcript.

  The segment cluster M62096_PEA_1_node_27 of the present invention is supported by 35 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M62096_PEA_1_T4, M62096_PEA_1_T5, M62096_PEA_1_T6, M62096_PEA_1_T7, M62096_PEA_1_T9, M62096_PEA_1_T13, and M62096_PEA_1_T14. Table 649 below describes the start and end positions of this segment on each transcript.

  The segment cluster M62096_PEA_1_node_29 of the present invention is supported by one library. The number of libraries was determined as described above. This segment can be found in the following transcript: M62096_PEA_1_T4. Table 650 below describes the start and end positions of this segment on each transcript.

  The segment cluster M62096_PEA_1_node_31 of the present invention is supported by 24 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M62096_PEA_1_T4, M62096_PEA_1_T5, M62096_PEA_1_T6, M62096_PEA_1_T7, M62096_PEA_1_T9, M62096_PEA_1_T13, and M62096_PEA_1_T14. Table 651 below describes the start and end positions of this segment on each transcript.

  The segment cluster M62096_PEA_1_node_34 of the present invention is supported by three libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: M62096_PEA_1_T14. Table 652 below describes the start and end positions of this segment on each transcript.

  The segment cluster M62096_PEA_1_node_36 of the present invention is supported by 26 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M62096_PEA_1_T4, M62096_PEA_1_T5, M62096_PEA_1_T6, M62096_PEA_1_T7, M62096_PEA_1_T9, and M62096_PEA_1_T13. Table 653 below describes the start and end positions of this segment on each transcript.

  The segment cluster M62096_PEA_1_node_38 of the present invention is supported by 24 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M62096_PEA_1_T4, M62096_PEA_1_T5, M62096_PEA_1_T6, M62096_PEA_1_T7, M62096_PEA_1_T9, and M62096_PEA_1_T13. Table 654 below describes the start and end positions of this segment on each transcript.

  The segment cluster M62096_PEA_1_node_40 of the present invention is supported by 21 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M62096_PEA_1_T4, M62096_PEA_1_T5, M62096_PEA_1_T6, M62096_PEA_1_T7, M62096_PEA_1_T9, and M62096_PEA_1_T13. Table 655 below describes the start and end positions of this segment on each transcript.

  The segment cluster M62096_PEA_1_node_48 of the present invention is supported by seven libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: M62096_PEA_1_T13. Table 656 below describes the start and end positions of this segment on each transcript.

  The segment cluster M62096_PEA_1_node_50 of the present invention is supported by three libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: M62096_PEA_1_T11 and M62096_PEA_1_T15. Table 657 below describes the start and end positions of this segment on each transcript.

  The segment cluster M62096_PEA_1_node_56 of the present invention is supported by one library. The number of libraries was determined as described above. This segment can be found in the following transcript: M62096_PEA_1_T15. Table 658 below describes the start and end positions of this segment on each transcript.

  The segment cluster M62096_PEA_1_node_60 of the present invention is supported by 13 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M62096_PEA_1_T4, M62096_PEA_1_T5, M62096_PEA_1_T6, M62096_PEA_1_T7, M62096_PEA_1_T9, and M62096_PEA_1_T11. Table 659 below describes the start and end positions of this segment on each transcript.

  The segment cluster M62096_PEA_1_node_65 of the present invention is supported by 51 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M62096_PEA_1_T4, M62096_PEA_1_T5, M62096_PEA_1_T6, M62096_PEA_1_T7, M62096_PEA_1_T9, and M62096_PEA_1_T11. Table 660 below describes the start and end positions of this segment on each transcript.

  The segment cluster M62096_PEA_1_node_69 of the present invention is supported by 85 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M62096_PEA_1_T4, M62096_PEA_1_T5, M62096_PEA_1_T6, M62096_PEA_1_T7, M62096_PEA_1_T9, and M62096_PEA_1_T11. Table 661 below describes the start and end positions of this segment on each transcript.

  The segment cluster M62096_PEA_1_node_71 of the present invention is supported by 178 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M62096_PEA_1_T4, M62096_PEA_1_T5, M62096_PEA_1_T6, M62096_PEA_1_T7, M62096_PEA_1_T9, and M62096_PEA_1_T11. Table 662 below describes the start and end positions of this segment on each transcript.

  According to an optional embodiment of the present invention, there is also provided a short segment associated with the above cluster. These segments are up to about 120 bp in length and are therefore included in the individual descriptions.

  The segment cluster M62096_PEA_1_node_1 according to the invention can be found in the transcripts below: M62096_PEA_1_T4, M62096_PEA_1_T13, and M62096_PEA_1_T14. Table 663 below describes the start and end positions of this segment on each transcript.

  The segment cluster M62096_PEA_1_node_4 of the present invention is supported by 12 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: M62096_PEA_1_T4, M62096_PEA_1_T5, M62096_PEA_1_T13, and M62096_PEA_1_T14. Table 664 below describes the start and end positions of this segment on each transcript.

  The segment cluster M62096_PEA_1_node_6 of the present invention is supported by 13 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: M62096_PEA_1_T4, M62096_PEA_1_T5, M62096_PEA_1_T13, and M62096_PEA_1_T14. Table 665 below describes the start and end positions of this segment on each transcript.

  The segment cluster M62096_PEA_1_node_7 of the present invention is supported by 19 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: M62096_PEA_1_T4, M62096_PEA_1_T5, M62096_PEA_1_T13, and M62096_PEA_1_T14. Table 666 below describes the start and end positions of this segment on each transcript.

  The segment cluster M62096_PEA_1_node_9 of the present invention is supported by 18 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: M62096_PEA_1_T4, M62096_PEA_1_T5, M62096_PEA_1_T13, and M62096_PEA_1_T14. Table 667 below describes the start and end positions of this segment on each transcript.

  The segment cluster M62096_PEA_1_node_11 of the present invention is supported by 22 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: M62096_PEA_1_T4, M62096_PEA_1_T5, M62096_PEA_1_T13, and M62096_PEA_1_T14. Table 668 below describes the start and end positions of this segment on each transcript.

  The segment cluster M62096_PEA_1_node_13 of the present invention is supported by 24 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: M62096_PEA_1_T4, M62096_PEA_1_T5, M62096_PEA_1_T13, and M62096_PEA_1_T14. Table 669 below describes the start and end positions of this segment on each transcript.

  The segment cluster M62096_PEA_1_node_21 of the present invention is supported by 33 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M62096_PEA_1_T4, M62096_PEA_1_T5, M62096_PEA_1_T6, M62096_PEA_1_T7, M62096_PEA_1_T9, M62096_PEA_1_T13, and M62096_PEA_1_T14. Table 670 below describes the start and end positions of this segment on each transcript.

  The segment cluster M62096_PEA_1_node_25 of the present invention is supported by three libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: M62096_PEA_1_T5 and M62096_PEA_1_T9. Table 671 below describes the start and end positions of this segment on each transcript.

  The segment cluster M62096_PEA_1_node_33 of the present invention is supported by 20 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M62096_PEA_1_T4, M62096_PEA_1_T5, M62096_PEA_1_T6, M62096_PEA_1_T7, M62096_PEA_1_T9, M62096_PEA_1_T13, and M62096_PEA_1_T14. Table 672 below describes the start and end positions of this segment on each transcript.

  The segment cluster M62096_PEA_1_node_42 of the present invention is supported by 17 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M62096_PEA_1_T4, M62096_PEA_1_T5, M62096_PEA_1_T6, M62096_PEA_1_T7, M62096_PEA_1_T9, and M62096_PEA_1_T13. Table 673 below describes the start and end positions of this segment on each transcript.

  The segment cluster M62096_PEA_1_node_44 of the present invention is supported by 19 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M62096_PEA_1_T4, M62096_PEA_1_T5, M62096_PEA_1_T6, M62096_PEA_1_T7, M62096_PEA_1_T9, and M62096_PEA_1_T13. Table 674 below describes the start and end positions of this segment on each transcript.

  The segment cluster M62096_PEA_1_node_47 of the present invention is supported by 21 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M62096_PEA_1_T4, M62096_PEA_1_T5, M62096_PEA_1_T6, M62096_PEA_1_T7, M62096_PEA_1_T9, and M62096_PEA_1_T13. Table 675 below describes the start and end positions of this segment on each transcript.

  Microarray (chip) data for this segment is also available, as follows. As described above, with respect to the clusters themselves, different oligonucleotides were tested for differential expression in different disease states, in particular cancer. The following oligonucleotides were found to reach this segment (for lung cancer) (shown in Table 676).

  The segment cluster M62096_PEA_1_node_51 of the present invention is supported by 11 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M62096_PEA_1_T4, M62096_PEA_1_T5, M62096_PEA_1_T6, M62096_PEA_1_T7, M62096_PEA_1_T9, M62096_PEA_1_T11, and M62096_PEA_1_T15. Table 677 below describes the start and end positions of this segment on each transcript.

  The segment cluster M62096_PEA_1_node_53 of the present invention is supported by 10 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M62096_PEA_1_T4, M62096_PEA_1_T5, M62096_PEA_1_T6, M62096_PEA_1_T7, M62096_PEA_1_T9, M62096_PEA_1_T11, and M62096_PEA_1_T15. Table 678 below describes the start and end positions of this segment on each transcript.

  The segment cluster M62096_PEA_1_node_55 of the present invention is supported by nine libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M62096_PEA_1_T4, M62096_PEA_1_T5, M62096_PEA_1_T6, M62096_PEA_1_T7, M62096_PEA_1_T9, M62096_PEA_1_T11, and M62096_PEA_1_T15. Table 679 below describes the start and end positions of this segment on each transcript.

  The segment cluster M62096_PEA_1_node_58 of the present invention is supported by nine libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M62096_PEA_1_T4, M62096_PEA_1_T5, M62096_PEA_1_T6, M62096_PEA_1_T7, M62096_PEA_1_T9, and M62096_PEA_1_T11. Table 680 below describes the start and end positions of this segment on each transcript.

  The segment cluster M62096_PEA_1_node_62 of the present invention is supported by 14 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M62096_PEA_1_T4, M62096_PEA_1_T5, M62096_PEA_1_T6, M62096_PEA_1_T7, M62096_PEA_1_T9, and M62096_PEA_1_T11. Table 681 below describes the start and end positions of this segment on each transcript.

  The segment cluster M62096_PEA_1_node_66 of the present invention is supported by 23 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M62096_PEA_1_T4, M62096_PEA_1_T5, M62096_PEA_1_T6, M62096_PEA_1_T7, M62096_PEA_1_T9, and M62096_PEA_1_T11. Table 682 below describes the start and end positions of this segment on each transcript.

  The segment cluster M62096_PEA_1_node_67 according to the invention can be found in the following transcripts: M62096_PEA_1_T4, M62096_PEA_1_T5, M62096_PEA_1_T6, M62096_PEA_1_T7, M62096_PEA_1_T9, and M62096_PEA_1_T11. Table 683 below describes the start and end positions of this segment on each transcript.

  The segment cluster M62096_PEA_1_node_68 according to the invention can be found in the following transcripts: M62096_PEA_1_T4, M62096_PEA_1_T5, M62096_PEA_1_T6, M62096_PEA_1_T7, M62096_PEA_1_T9, and M62096_PEA_1_T11. Table 684 below describes the start and end positions of this segment on each transcript.

  The segment cluster M62096_PEA_1_node_70 of the present invention is supported by 55 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M62096_PEA_1_T4, M62096_PEA_1_T5, M62096_PEA_1_T6, M62096_PEA_1_T7, M62096_PEA_1_T9, and M62096_PEA_1_T11. Table 685 below describes the start and end positions of this segment on each transcript.

Mutated protein alignment against previously known proteins:
Sequence name: KF5C_HUMAN

Sequence documentation:

Alignment of: M62096_PEA_1_P4 x KF5C_HUMAN ..

Alignment segment 1/1:

Quality: 6936.00 Escore: 0
Matching length: 719 Total length: 719
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
7 VSKTGAEGAVLDEAKNINKSLSALGNVISALAEGTKTHVPYRSKSMTRIL 56
||||||||||||||||||||||||||||||||||||||||
239 VSKTGAEGAVLDEAKNINKSLSALGNVISALAEGTKTHVPYRDSKTMRIL 288
....
57 QDSLGGNCRTTIVICCSPSVFNEAETKSTLMFGQRAKTIKNTVSVNLELT 106
||||||||||||||||||||||||||||||||||||||||
289 QDSLGGNCRTTIVICCSSPSVFNEAETKSTLMFGQRAKTIKNTVSVNLELT 338
....
107 AEEWKKKYEKEKEKNKTLKNVIQHLEMELNRWRNGEAVPDEQISAKDQK 156
||||||||||||||||||||||||||||||||||||||||
339 AEEWKKKYEKEKEKNKTLKNVIQHLEMELNRWRNGEAVPEDEQISAKDQK 388
....
157 NLEPCDNTPIIDNIAPV VAGISTEEKEKYDEEISSLYRQLDDKDDEINQQ 206
||||||||||||||||||||||||||||||||||||||||
389 NLEPCDNTPIIDNIAPV VAGISTEEKEKYDEEISSLYRQLDDKDDEINQQ 438
....
207 SQLAEKLKQQMLDQDELLASTRRDYEKIQEELTRLQIENEAAKDEVKEVL 256
||||||||||||||||||||||||||||||||||||||||
439 SQLAEKLKQQMLDQDELLASTRRDYEKIQEELTRLQIENEAAKDEVKEVL 488
....
257 QALEELAVNYDQKSQEVEDKTRANEQLTDELAQKTTTLTTTQRELSQLQE 306
||||||||||||||||||||||||||||||||||||||||
489 QALEELAVNYDQKSQEVEDKTRANEQLTDELAQKTTTLTTTQRELSQLQE 538
....
307 LSNHQKKRATEILNLLLKDLGEIGGIIGTNDVKTLADVNGVIEEEFTMAR 356
||||||||||||||||||||||||||||||||||||||||
539 LSNHQKKRATEILNLLLKDLGEIGGIIGTNDVKTLADVNGVIEEEFTMAR 588
....
357 LYISKMKSEVKSLVNRSKQLESAQMDSNRKMNASERELAACQLLISQHEA 406
||||||||||||||||||||||||||||||||||||||||
589 LYISKMKSEVKSLVNRSKQLESAQMDSNRKMNASERELAACQLLISQHEA 638
....
407 KIKSLTTDYMQNMQQRRQREESQDSLSEELAKLAQEKMHEVSFQDKEKE 456
||||||||||||||||||||||||||||||||||||||||
639 KIKSLTDYMQNMQQRRQREESQDSLSEELAKLAQEKMHEVSFQDKEKE 688
....
457 HLTRLQDAEEMKKALEQQMESHREAHQKQLSLRRDEIEEKQKIIDEIRDL 506
||||||||||||||||||||||||||||||||||||||||
689 HLTRLQDAEEMKKALEQQMESHREAHQKQLSLRRDEIEEKQKIIDEIRDL 738
....
507 NQKLQLEQEKLSSDYNKLKIEDQ EREMKLEKLLLLNDKREQAREDLKGLE 556
||||||||||||||||||||||||||||||||||||||||
739 NQKLQLEQEKLSSDYNKLKIEDQ EREMKLEKLLLLNDKREQAREDLKGLE 788
....
557 ETVSRELQTLHNLRKLFVQDLTTRVKKSVELDNDDGGGSAAQKQKISFLE 606
||||||||||||||||||||||||||||||||||||||||
789 ETVSRELQTLHNLRKLFVQDLTTRVKKSVELDNDDGGGSAAQKQKISFLE 838
....
607 NNLEQLTKVHKQLVRDNADLRCELPKLEKLRATAA VKALESALKEAKE 656
||||||||||||||||||||||||||||||||||||||||
839 NNLEQLTKVHKQLVRDNADLRCELPKLEKLRATAA VKALESALKEAKE 888
....
657 NAMRDRKRYQQEVDRIKEAVRAKNMARRAHSAQIAKPRPGHYPASSPTA 706
||||||||||||||||||||||||||||||||||||||||
889 NAMRDRKRYQQEVDRIKEAVRAKNMARRAHSAQIAKPRPGYPASSPTA 938
.
707 VHAIRGGGGSSNSTHTHYQK 725
||||||||||||||||||
939 VHAIRGGGGSSNSTHYQK 957






Sequence name: KF5C_HUMAN

Sequence documentation:

Alignment of: M62096_PEA_1_P5 x KF5C_HUMAN ..

Alignment segment 1/1:

Quality: 6520.00 Escore: 0
Matching length: 674 Total length: 674
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MTRILQDSLGGNCRTTIVICCSSPSVFNEAETKSTLMFGQRAKTIKNTSVSV 50
||||||||||||||||||||||||||||||||||||||||
284 MTRILQDSLGGNCRTTIVICCSSPSVFNEAETKSTLMFGQRAKTIKNTVSV 333
....
51 NLELTAEEWKKKYEKEK EK NKTLKNVIQHLEMELNRWRNGEAVPDEQIS 100
||||||||||||||||||||||||||||||||||||||||
334 NLELTAEEWKKKYEKEK EK NKTLKNVIQHLEMELNRWRNGEAVPPEQIS 383
....
101 AKDQK NLEPCD NTP IIDNIAPV VAGISTEEKEKYDEEISSLYRQLDDKDD 150
||||||||||||||||||||||||||||||||||||||||
384 AKDQKN LEPCDNTPIID NIAPV VAGISTEEKEKYDEEISSLYRQLDDKDD 433
....
151 EINQQSQLAEKLKQQMLDQDELLASTRRDYEKIQEELTRLQIENEAAKDE 200
||||||||||||||||||||||||||||||||||||||||
434 EINQQSQLAEKLKQQMLDQDELLASTRRDYEKIQEELTRLQIENEAAKDE 483
....
201 VKEVLQALEELAVNYDQKSQEVEDKTRANEQLTDELAQKTTTLTTTQREL 250
||||||||||||||||||||||||||||||||||||||||
484 VKEVLQALEELAVNYDQKSQEVEDKTRANEQLTDELAQKTTTLTTTQREL 533
....
251 SQLQELSNHQKKRATEILNLLLKDLGEIGGIIGTNDVKTLADVNGVIEEE 300
||||||||||||||||||||||||||||||||||||||||
534 SQLQELSNHQKKRATEILNLLLKDLGEIGGIIGTNDVKTLADVNGVIEEE 583
....
301 FTMARLYISKMKSEVKSLVNRSKLESAQMDSNRKMNASERELAACQLLI 350
||||||||||||||||||||||||||||||||||||||||
584 FTMARLYISKMKSEVKSLVNRSKLESAQMDSNRKMNASERELAACQLLI 633
....
351 SQHEAKIKSLTDYMQNMEQKRRQLEESQDSLSEELAKLRAQEKMHEVSFQ 400
||||||||||||||||||||||||||||||||||||||||
634 SQHEAKIKSLTDYMQNMEQKRRQLEESQDSLSEELAKLAQEKMHEVSFQ 683
....
401 DKEKEHLTRLQDAEEMCKALEQQMESHREAHQKQLSRLRDEIEEKQKIID 450
||||||||||||||||||||||||||||||||||||||||
684 DKEKEHLTRLQDAEEMCKALEQQMESHREAHQKQLSRLRDEIEEKQKIID 733
....
451 EIRDLNQKLQLEQEKLSSDYNKLKIEDQ EREMKLEKLLLLNDKREQARED 500
||||||||||||||||||||||||||||||||||||||||
734 EIRDLNQKLQLEQEKLSSDYNKLKIEDQ EREMKLEKLLLLNDKREQARED 783
....
501 LKGLEETVSRELQTLHNLRKLFVQDLTTRVKKSVELDNDDGGGSAAQKQK 550
||||||||||||||||||||||||||||||||||||||||
784 LKGLEETVSRELQTLHNLRKLFVQDLTTRVKKSVELDNDDGGGSAAQKQK 833
....
551 ISFLENNLEQLTKVHKQLVRDNADLRCELPKLEKLRATAERVKALESAL 600
||||||||||||||||||||||||||||||||||||||||
834 ISFLENNLEQLTKVHKQLVRDNADLRCELPKLEKLRATAERVKALESAL 883
....
601 KEAKENAMRDRKRYQQEVDRIKEAVRAKNMARRAHSAQIAKPRPGHYPA 650
||||||||||||||||||||||||||||||||||||||||
884 KEAKENAMRDRKRYQQEVDRIKEAVRAKNMARRAHSAQIAKPRPGHYPA 933
.
651 SSPTAVHAIRGGGGSSNSTHYQK 674
|||||||||||||||||||||||
934 SSPTAVHAIRGGGGSSNSTHYQK 957






Sequence name: KF5C_HUMAN

Sequence documentation:

Alignment of: M62096_PEA_1_P3 x KF5C_HUMAN ..

Alignment segment 1/1:

Quality: 5726.00 Escore: 0
Matching length: 593 Total length: 593
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MELNRWRNGEAVPEDEQISAKDQ KNLE PCD NTP IID NIAP V VAGISTEEK 50
||||||||||||||||||||||||||||||||||||||||
365 MELNRWRNGEAVPEDEQISAKDQ KNLE PCD NTP IID NIAP V VAGISTEEK 414
....
51 EKYDEEISSLYRQLDDKDDEINQQSQLAEKLKQQMLDQDELLASTRRDYE 100
||||||||||||||||||||||||||||||||||||||||
415 EKYDEEISSLYRQLDDKDDEINQQSQLAEKLKQQMLDQDELLASTRRDYE 464
....
101 KIQEELTRLQIENEAAKDEVKEVLQALEELAVNYDQKSQEVEDKTRANEQ 150
||||||||||||||||||||||||||||||||||||||||
465 KIQEELTRLQIENEAAKDEVKEVLQALEELAVNYDQKSQEVEDKTRANEQ 514
....
151 LTDELAQKTTTLTTTQRELSQLQELSNHQKKRATEILNLLLKDLGEIGGI 200
||||||||||||||||||||||||||||||||||||||||
515 LTDELAQKTTTLTTTQRELSQLQELSNHQKKRATEILNLLLKDLGEIGGI 564
....
201 IGTNDVKTLADVNGVIEEEFTMARLYISKMKSEVKSLVNRSKQLESAQMD 250
||||||||||||||||||||||||||||||||||||||||
565 IGTNDVKTLADVNGVIEEEFTMARLYISKMKSEVKSLVNRSKLESAQMD 614
....
251 SNRKMNASERELAACQLLISQHEAKIKSLTDYMQNMEQKRRQLEESQDSL 300
||||||||||||||||||||||||||||||||||||||||
615 SNRKMNASERELAACQLLISQHEAKIKSLTDYMQNMEQKRRQLEESQDSL 664
....
301 SEELAKLRAQEKMHEVSF QDKEKEHLTRLQDAEEMCKALEQQMESHREAH 350
||||||||||||||||||||||||||||||||||||||||
665 SEELAKLRAQEKMHEVSF QDKEKEHLTRLQDAEEMCKALEQQMESHREAH 714
....
351 QKQSLSRLRDEIEEKQKIIDEIRDLNQKLQLEQEKLSDSYNKLKIEDQERE 400
||||||||||||||||||||||||||||||||||||||||
715 QKQSLSRLRDEIEEKQKIIDEIRDLNQ KLQLEQEKLSDSYNKLKIEDQERE 764
....
401 MKLEKLLLLNDKREQAREDLKGLEETVSRELQTLHNLRKLFVQDLTTRVK 450
||||||||||||||||||||||||||||||||||||||||
765 MKLEKLLLLNDKREQAREDLKGLEETVSRELQTLHNLRKLFVQDLTTRVK 814
....
451 KSVELDNDDGGGSAAQKQ KISFLENNLEQLTKVHKQLVRDNADLRCELPK 500
||||||||||||||||||||||||||||||||||||||||
815 KSVELDNDDGGGSAAQKQ KISFLENNLEQLTKVHKQLVRDNADLRCELPK 864
....
501 LEKRLATAERVKALESALKEAKENAMRDRKRYQQEVDRIKEAVRAKNMA 550
||||||||||||||||||||||||||||||||||||||||
865 LEKRLATAERVKALESALKEAKENAMRDRKRYQQEVDRIKEAVRAKNMA 914
....
551 RRAHSAQIAKPRPGYPASSPTAVHAIRGGGGSSNSTHYQK 593
|||||||||||||||||||||||||||||||||||||
915 RRAHSAQ IAKPIRPGHYPASSPTAVHAIRGGGGSSNSTHYQK 957






Sequence name: KF5C_HUMAN

Sequence documentation:

Alignment of: M62096_PEA_1_P7 x KF5C_HUMAN ..

Alignment segment 1/1:

Quality: 2117.00 Escore: 0
Matching length: 220 Total length: 220
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
20 LNQKLQLEQEKLSSDYNKLKIEDQ EREMKLEKLLLLNDKREQAREDLKGL 69
||||||||||||||||||||||||||||||||||||||||
738 LNQKLQLEQEKLSSDYNKLKIEDQ EREMKLEKLLLLNDKREQAREDLKGL 787
....
70 EETVSRELQTLHNLRKLFVQDLTTRVKKSVELDNDDGGGSAAQKQKISFL 119
||||||||||||||||||||||||||||||||||||||||
788 EETVSRELQTLHNLRKLFVQDLTTRVKKSVELDNDDGGGSAAQKQKISFL 837
....
120 ENNLEQLTKVHKQLVRDNADLRCELPKLEKLRATAA VKALESALKEAK 169
||||||||||||||||||||||||||||||||||||||||
838 ENNLEQLTKVHKQLVRDNADLRCELPKLEKLRATAA VKALESALKEAK 887
....
170 ENAMRDRKRYQQEVDRIKEAVRAKNMARRAHSAQIAKPRPGYPASSPT 219
||||||||||||||||||||||||||||||||||||||||
888 ENAMRDRKRYQQEVDRIKEAVRAKNMARRAHSAQIAKPRPGYPASSPT 937
.
220 AVHAIRGGGGSSNSTHYQK 239
|||||||||||||||||||
938 AVHAIRGGGGSSNSTHYQK 957






Sequence name: KF5C_HUMAN

Sequence documentation:

Alignment of: M62096_PEA_1_P8 x KF5C_HUMAN ..

Alignment segment 1/1:

Quality: 7146.00 Escore: 0
Matching length: 737 Total length: 737
Matching Percent Similarity: 100.00 Matching Percent Identity: 99.86
Total Percent Similarity: 100.00 Total Percent Identity: 99.86
Gaps: 0

Alignment:
....
1 1
||||||||||||||||||||||||||||||||||||||||
1 1
....
51 RVLPPTNTQEQVYNACAKQIVKDVLEGYNGTIFAYGQTSSGKTHTMEGKL 100
||||||||||||||||||||||||||||||||||||||||
51 RVLPPTNTQEQVYNACAKQIVKDVLEGYNGTIFAYGQTSSGKTHTMEGKL 100
....
101 HDPQLMGIIPRIAHDIFDHIYSMDENLEFHIKVSYFEIYLDKIRDLLDVS 150
||||||||||||||||||||||||||||||||||||||||
101 HDPQLMGIIPRIAHDIFDHIYSMDENLEFHIKVSYFEIYLDKIRDLLDVS 150
....
151 KTNLAVHEDKNRVPYVKGCTERFVSSPEEVMDVIDEGKANRHVAVTNMNE 200
||||||||||||||||||||||||||||||||||||||||
151 KTNLAVHEDKNRVPYVKGCTERFVSSPEEVMDVIDEGKANRHVAVTNMNE 200
....
201 HSSRSHSIFLINIKQENVETEKKLSGKLYLVDLAGSEKVSKTGAEGAVLD 250
||||||||||||||||||||||||||||||||||||||||
201 HSSRSHSIFLINIKQENVETEKKLSGKLYLVDLAGSEKVSKTGAEGAVLD 250
....
251 EAKNINKSLSALGNNVISALAEGTKTHVPYRDSKTMRILQDSLGGNCRTTI 300
||||||||||||||||||||||||||||||||||||||||
251 EAKNINKSLSALGNNVISALAEGTKTHVPYRDSKTMRILQDSLGGNCRTTI 300
....
301 VICCSSPSVFNEAETKSTLMFGQRAKTIKNTVSVNLELTAEEWKKKYEK 350
||||||||||||||||||||||||||||||||||||||||
301 VICCSSPSVFNEAETKSTLMFGQRAKTIKNTVSVNLELTAEEWKKKYEK 350
....
351 EKNKTLKNVIQHLEMELNRWRNGEAVPPEQISAKDQ KNLE PCD NTPIID 400
||||||||||||||||||||||||||||||||||||||||
351 EKNKTLKNVIQHLEMELNRWRNGEAVPPEQISAKDQ KNLE PCD NTPIID 400
....
401 NIAPVVAGISTEEKEKYDEEISSLYRQLDDKDDEINQQSQLAEKLKQQ 450
||||||||||||||||||||||||||||||||||||||||
401 NIAPVVAGISTEEKEKYDEEISSLYRQLDDKDDEINQQSQLAEKLKQQ 450
....
451 DQDELLASTRRDYEKIQEELTRLQIENEAAKDEVKEVLQALEELAVNYDQ 500
||||||||||||||||||||||||||||||||||||||||
451 DQDELLASTRRDYEKIQEELTRLQIENEAAKDEVKEVLQALEELAVNYDQ 500
....
501 KSQEVEDKTRANEQLTDELAQKTTTLTTTQRELSQLQELSNHQKKRATEI 550
||||||||||||||||||||||||||||||||||||||||
501 KSQEVEDKTRANEQLTDELAQKTTTLTTTQRELSQLQELSNHQKKRATEI 550
....
551 LNLLLKDLGEIGGIIGTNDVKTLADVNGVIEEEFTMARLYISKMKSEVKS 600
||||||||||||||||||||||||||||||||||||||||
551 LNLLLKDLGEIGGIIGTNDVKTLADVNGVIEEEFTMARLYISKMKSEVKS 600
....
601 LVNRSKQLESAQMDSNRKMNASERELAACQLLISQHEAKIKSLTDYMQNM 650
||||||||||||||||||||||||||||||||||||||||
601 LVNRSKQLESAQMDSNRKMNASERELAACQLLISQHEAKIKSLTDYMQNM 650
....
651 EQKRRQLEESQDSLSEELAKLRAQEKMHEVSFQDKEKEHLTRLQDAEEMK 700
||||||||||||||||||||||||||||||||||||||||
651 EQKRRQLEESQDSLSEELAKLRAQEKMHEVSFQDKEKEHLTRLQDAEEMK 700
....
701 KALEQQMESHREAHQKQLSLRRDEIEEKQKIIDEIRE 737
||||||||||||||||||||||||||||||: |
701 KALEQQMESHREAHQKQLSLRLRDEIEEKQKIIDEIRD 737






Sequence name: KF5C_HUMAN

Sequence documentation:

Alignment of: M62096_PEA_1_P9 x KF5C_HUMAN ..

Alignment segment 1/1:

Quality: 4434.00 Escore: 0
Matching length: 454 Total length: 454
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 1
||||||||||||||||||||||||||||||||||||||||
1 1
....
51 RVLPPTNTQEQVYNACAKQIVKDVLEGYNGTIFAYGQTSSGKTHTMEGKL 100
||||||||||||||||||||||||||||||||||||||||
51 RVLPPTNTQEQVYNACAKQIVKDVLEGYNGTIFAYGQTSSGKTHTMEGKL 100
....
101 HDPQLMGIIPRIAHDIFDHIYSMDENLEFHIKVSYFEIYLDKIRDLLDVS 150
||||||||||||||||||||||||||||||||||||||||
101 HDPQLMGIIPRIAHDIFDHIYSMDENLEFHIKVSYFEIYLDKIRDLLDVS 150
....
151 KTNLAVHEDKNRVPYVKGCTERFVSSPEEVMDVIDEGKANRHVAVTNMNE 200
||||||||||||||||||||||||||||||||||||||||
151 KTNLAVHEDKNRVPYVKGCTERFVSSPEEVMDVIDEGKANRHVAVTNMNE 200
....
201 HSSRSHSIFLINIKQENVETEKKLSGKLYLVDLAGSEKVSKTGAEGAVLD 250
||||||||||||||||||||||||||||||||||||||||
201 HSSRSHSIFLINIKQENVETEKKLSGKLYLVDLAGSEKVSKTGAEGAVLD 250
....
251 EAKNINKSLSALGNNVISALAEGTKTHVPYRDSKTMRILQDSLGGNCRTTI 300
||||||||||||||||||||||||||||||||||||||||
251 EAKNINKSLSALGNNVISALAEGTKTHVPYRDSKTMRILQDSLGGNCRTTI 300
....
301 VICCSSPSVFNEAETKSTLMFGQRAKTIKNTVSVNLELTAEEWKKKYEK 350
||||||||||||||||||||||||||||||||||||||||
301 VICCSSPSVFNEAETKSTLMFGQRAKTIKNTVSVNLELTAEEWKKKYEK 350
....
351 EKNKTLKNVIQHLEMELNRWRNGEAVPPEQISAKDQ KNLE PCD NTPIID 400
||||||||||||||||||||||||||||||||||||||||
351 EKNKTLKNVIQHLEMELNRWRNGEAVPPEQISAKDQ KNLE PCD NTPIID 400
....
401 NIAPVVAGISTEEKEKYDEEISSLYRQLDDKDDEINQQSQLAEKLKQQ 450
||||||||||||||||||||||||||||||||||||||||
401 NIAPVVAGISTEEKEKYDEEISSLYRQLDDKDDEINQQSQLAEKLKQQ 450

451 DQDE 454
|||||
451 DQDE 454






Sequence name: KF5C_HUMAN

Sequence documentation:

Alignment of: M62096_PEA_1_P10 x KF5C_HUMAN ..

Alignment segment 1/1:

Quality: 747.00 Escore: 0
Matching length: 78 Total length: 78
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
20 LNQKLQLEQEKLSSDYNKLKIEDQ EREMKLEKLLLLNDKREQAREDLKGL 69
||||||||||||||||||||||||||||||||||||||||
738 LNQKLQLEQEKLSSDYNKLKIEDQ EREMKLEKLLLLNDKREQAREDLKGL 787
.
70 EETVSRELQTLHNLRKLFVQDLTTRVKK 97
||||||||||||||||||||||||||
788 EETVSRELQTLHNLRKLFVQDLTTRVKK 815






Sequence name: KF5C_HUMAN

Sequence documentation:

Alignment of: M62096_PEA_1_P11 x KF5C_HUMAN ..

Alignment segment 1/1:

Quality: 3634.00 Escore: 0
Matching length: 372 Total length: 372
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 1
||||||||||||||||||||||||||||||||||||||||
1 1
....
51 RVLPPTNTQEQVYNACAKQIVKDVLEGYNGTIFAYGQTSSGKTHTMEGKL 100
||||||||||||||||||||||||||||||||||||||||
51 RVLPPTNTQEQVYNACAKQIVKDVLEGYNGTIFAYGQTSSGKTHTMEGKL 100
....
101 HDPQLMGIIPRIAHDIFDHIYSMDENLEFHIKVSYFEIYLDKIRDLLDVS 150
||||||||||||||||||||||||||||||||||||||||
101 HDPQLMGIIPRIAHDIFDHIYSMDENLEFHIKVSYFEIYLDKIRDLLDVS 150
....
151 KTNLAVHEDKNRVPYVKGCTERFVSSPEEVMDVIDEGKANRHVAVTNMNE 200
||||||||||||||||||||||||||||||||||||||||
151 KTNLAVHEDKNRVPYVKGCTERFVSSPEEVMDVIDEGKANRHVAVTNMNE 200
....
201 HSSRSHSIFLINIKQENVETEKKLSGKLYLVDLAGSEKVSKTGAEGAVLD 250
||||||||||||||||||||||||||||||||||||||||
201 HSSRSHSIFLINIKQENVETEKKLSGKLYLVDLAGSEKVSKTGAEGAVLD 250
....
251 EAKNINKSLSALGNNVISALAEGTKTHVPYRDSKTMRILQDSLGGNCRTTI 300
||||||||||||||||||||||||||||||||||||||||
251 EAKNINKSLSALGNNVISALAEGTKTHVPYRDSKTMRILQDSLGGNCRTTI 300
....
301 VICCSSPSVFNEAETKSTLMFGQRAKTIKNTVSVNLELTAEEWKKKYEK 350
||||||||||||||||||||||||||||||||||||||||
301 VICCSSPSVFNEAETKSTLMFGQRAKTIKNTVSVNLELTAEEWKKKYEK 350
.
351 EKNKTLKNVIQHLEMELNRWRN 372
|||||||||||||||||||||
351 EKNKTLKNVIQHLEMELNRWRN 372






Sequence name: KF5C_HUMAN

Sequence documentation:

Alignment of: M62096_PEA_1_P12 x KF5C_HUMAN ..

Alignment segment 1/1:

Quality: 3145.00 Escore: 0
Matching length: 323 Total length: 323
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 1
||||||||||||||||||||||||||||||||||||||||
1 1
....
51 RVLPPTNTQEQVYNACAKQIVKDVLEGYNGTIFAYGQTSSGKTHTMEGKL 100
||||||||||||||||||||||||||||||||||||||||
51 RVLPPTNTQEQVYNACAKQIVKDVLEGYNGTIFAYGQTSSGKTHTMEGKL 100
....
101 HDPQLMGIIPRIAHDIFDHIYSMDENLEFHIKVSYFEIYLDKIRDLLDVS 150
||||||||||||||||||||||||||||||||||||||||
101 HDPQLMGIIPRIAHDIFDHIYSMDENLEFHIKVSYFEIYLDKIRDLLDVS 150
....
151 KTNLAVHEDKNRVPYVKGCTERFVSSPEEVMDVIDEGKANRHVAVTNMNE 200
||||||||||||||||||||||||||||||||||||||||
151 KTNLAVHEDKNRVPYVKGCTERFVSSPEEVMDVIDEGKANRHVAVTNMNE 200
....
201 HSSRSHSIFLINIKQENVETEKKLSGKLYLVDLAGSEKVSKTGAEGAVLD 250
||||||||||||||||||||||||||||||||||||||||
201 HSSRSHSIFLINIKQENVETEKKLSGKLYLVDLAGSEKVSKTGAEGAVLD 250
....
251 EAKNINKSLSALGNNVISALAEGTKTHVPYRDSKTMRILQDSLGGNCRTTI 300
||||||||||||||||||||||||||||||||||||||||
251 EAKNINKSLSALGNNVISALAEGTKTHVPYRDSKTMRILQDSLGGNCRTTI 300
.
301 VICCSSPSVFNEAETKSTLMFGQR 323
||||||||||||||||||||||
301 VICCSSPSVFNEAETKSTLMFGQR 323

Expression of homo-Sapiens protein tyrosine phosphatase receptor type S (PTPRS) M62069 transcripts detectable by an amplicon as shown in sequence name M62069 seg19 in normal and cancerous lung tissue seg19, M62069 seg19 amplicon (SEQ ID NO: 1657), and M62069 seg 19 F The expression of homo sapiens protein tyrosine phosphatase receptor type S (PTPRS) transcripts detectable by (SEQ ID NO: 1655) and M62069 seg 19 R (SEQ ID NO: 1656) primers was measured by real-time PCR. In parallel, four housekeeping genes-PBGD (GenBank Accession No. BC019323, Amplicon – PBGD-Amplicon, SEQ ID No. 334), HPRT1 (GenBank Accession No. NM_000194, Amplicon – HPRT1- Amplicons, SEQ ID NO: 1297), Ubiquitin (GenBank Accession No. BC000449, Amplicon – Ubiquitin-Amplicon SEQ ID NO: 328), and SDHA (GenBank Accession No. NM_004168, Amplicon – SDHA-Amplicon SEQ ID NO: 331) was similarly measured. For each RT sample, the expression of the amplicon was normalized to the geometric mean of the housekeeping gene dose. Normalized PM samples by dividing the normalized volume of each RT sample by the median volume of normal postmortem (PM) samples (sample numbers 47-50, 90-93, 96-99, Table 2 above) Magnifications of upregulation of each sample to the median of were obtained.

  FIG. 65 is a histogram showing over expression of the Homo sapiens protein tyrosine phosphatase receptor S type (PTPRS) transcript in cancerous lung samples compared to normal samples. Values represent the average of duplicate experiments. Error bars indicate the obtained minimum and maximum values.

  As apparent from FIG. 65, the expression of the homo-Sapiens protein tyrosine phosphatase receptor type S (PTPRS) transcript detectable by the above amplicon in the cancer sample is a non-cancerous sample (sample numbers 47 to 50, 90) ~ 93, 96-99 (Table 2) were significantly higher. Apparently, at least 5-fold overexpression was found in 2 out of 15 adenocarcinoma samples and 8 out of 8 small cell carcinoma samples.

  Primer pairs are also optionally and preferably included within the scope of the present invention, for example, in the above experiments the following primers were used only as non-limiting examples of suitable primer pairs: M62069 seg19F forward primer and M62069 seg19 R reverse Direction primer.

  The present invention also preferably includes any amplicon obtained by use of any suitable primer pair (e.g. in the above experiments) and obtained the following amplicons only as a non-limiting illustration of a suitable amplicon : M62069 seg19.

Forward primer-M62069seg19F (SEQ ID NO: 1655): GCTGATTGTCCCCATGAAGG
Reverse primer-M62069 seg 19 (SEQ ID NO: 1656): TGGCATACGGGAACTCAGTG
Amplicon (SEQ ID NO: 1657): GCTGATTGTCCCCATGAAGGCCCAGCCTTGAAATCTTGGTCAGTCTCCTACTAACTG TATGATTGATCCCACTTATTGCACTACATCACTGAGTTCCCCGTATGC

Expression of homo-sapiens protein tyrosine phosphatase receptor type S (PTPRS) M62069 transcripts detectable by an amplicon as shown in sequence name M62069 seg29 in normal and cancerous lung tissue seg29, M62069 seg29 amplicon (SEQ ID NO: 1660), and M62069 seg29 F The expression of homo sapiens protein tyrosine phosphatase receptor type S (PTPRS) transcripts detectable by (SEQ ID NO: 1658) and M62069 seg 29 R (SEQ ID NO: 1659) primers was measured by real-time PCR. In parallel, four housekeeping genes-PBGD (GenBank Accession No. BC019323, Amplicon – PBGD-Amplicon, SEQ ID No. 334), HPRT1 (GenBank Accession No. NM_000194, Amplicon – HPRT1- Amplicons, SEQ ID NO: 1297), Ubiquitin (GenBank Accession No. BC000449, Amplicon – Ubiquitin-Amplicon SEQ ID NO: 328), and SDHA (GenBank Accession No. NM_004168, Amplicon – SDHA-Amplicon SEQ ID NO: 331) was similarly measured. For each RT sample, the expression of the amplicon was normalized to the geometric mean of the housekeeping gene dose. Normalized PM samples by dividing the normalized volume of each RT sample by the median volume of normal postmortem (PM) samples (sample numbers 47-50, 90-93, 96-99, Table 2 above) Magnifications of upregulation of each sample to the median of were obtained.

  FIG. 66 is a histogram showing over expression of the Homo sapiens protein tyrosine phosphatase receptor type S (PTPRS) transcript in cancerous lung samples compared to normal samples. Values represent the average of duplicate experiments. Error bars indicate the obtained minimum and maximum values.

  As apparent from FIG. 66, the expression of the homo-Sapiens protein tyrosine phosphatase receptor type S (PTPRS) transcript detectable by the above amplicon in a cancer sample is a non-cancerous sample (sample numbers 47 to 50, 90) ~ 93, 96-99 (Table 2) were significantly higher. Clearly, at least 5-fold overexpression was found in 2 out of 15 adenocarcinoma samples and 7 out of 8 small cell carcinoma samples.

  Primer pairs are also optionally and preferably included within the scope of the present invention, for example, in the above experiments the following primers were used only as non-limiting examples of suitable primer pairs: M62069 seg 29 F forward primer and M 620 69 seg 29 R reverse Direction primer.

  The present invention also preferably includes any amplicon obtained by use of any suitable primer pair (e.g. in the above experiments) and obtained the following amplicons only as a non-limiting illustration of a suitable amplicon : M62069 seg 29.

Forward primer-M62069seg29F: ATTGAATAATTCAGCACCTGAGGC
Reverse primer-M62069 seg 29 R: TTCATATGGCTACTCCCC ACCT
Amplicon: ATTGAATAATTCAGCACCTGAGGCTGGTGATGATTCTTTGCAATTTGGCAGGAATGGGAGAGTCGGAGCAGTAGTTGGCAAGGTGGGGAGCCATATGAA

Description of Cluster M78076 Cluster M78076 features 9 transcripts of interest and 35 segments, the names of which are shown in Tables 686 and 687 respectively, and the sequence itself is shown at the end of the application. Selected protein variants are shown in Table 688.

  These sequences are known proteins called amyloid-like protein 1 precursor (SwissProt accession identifier APP1_HUMAN, also known as synonym APLP, APLP-1), which is a known protein, previously known herein as a protein (sequence No. 1439).

  Protein Amyloid-like protein 1 precursor is known or is considered to have the following functions: It may play a role in postsynaptic function. The C-terminal gamma secretase processing fragment (ALID1) activates transcriptional activation by APBB1 (Fe65) binding (by similarity). Related to JIP signal conversion through C-terminal binding. It can interact with cellular G protein signaling pathways. Neurite outgrowth can be modulated by binding to extracellular matrix components such as heparin and type I collagen. The γ-CTF peptide C30 is a potent enhancer of neural apoptosis (by similarity). The sequence of the protein amyloid-like protein 1 precursor is shown at the end of the application as "amyloid-like protein 1 precursor amino acid sequence". Known polymorphisms of this sequence are shown in Table 689.

  The localization of the protein amyloid-like protein 1 precursor is considered to be a type I membrane protein. C-terminal processing at the Golgi complex.

  The following GO annotation applies to previously known proteins. The following annotations have been found: annotation related to biological processes endocytosis, apoptosis, cell adhesion, neurogenesis, cell death, protein binding annotated related to molecular function, heparin binding And basement membranes that are annotations related to cellular components, coated pits, integral membrane proteins.

  GO assignments can be made at one or more http: // www. expasy. SwissProt / TremBl Protein knowledgebase available from ch / sprot / or http: // www. ncbi. nlm. nih. Depends on Locuslink available from gov / projects / LocusLink /.

  As mentioned above, cluster M78076 is characterized by the nine transcripts listed in Table 1 above. These transcripts encode proteins which are variants of the protein amyloid-like protein 1 precursor. A description of each mutein of the invention is provided herein.

  The mutein M78076_PEA_1_P3 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript M78076_PEA_1_T2. An alignment to a known protein (amyloid-like protein 1 precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of the comparison between M78076_PEA_1_P3 and APP1_HUMAN 1. Corresponding to amino acids 1 to 517 of APP1_HUMAN, corresponding to amino acids 1 to 517 of M78076_PEA_1_P3 MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGLCGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPMERWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHT The first amino acid sequence at least 90% homologous to EibuibuijikeibuitiPitiPiaruPitidijibuidiaiwaiefujiemuPijiiaiesuieichiijiefueruarueikeiemudieruiiaruaruemuarukyuaienuibuiemuaruidaburyueiemueidienukyuesukeienueruPikeieidiarukyueieruenuieichiefukyuesuaierukyutieruiikyubuiesujiiarukyuaruerubuiitieichieitiarubuiaieieruaienudikyuaruarueieieruijiefuerueieierukyueidiPiPikyueiiarubuieruerueieruaruaruwaieruarueiikyukeiikyuarueichitieruarueichiwaikyueichibuieieibuidiPiikeieikyukyuemuaruefukyubuieichitieichierukyubuiaiiiarubuienukyuesuerujieruerudikyuenuPieichierueikyuieruaruPikyuaikyuieruerueichiesuieichieruJipiSELEAPAPGGSSEDKGGLQPPDSKD, polypeptide at least 70% with the sequence GE corresponding to amino acids 518-519 of M78076_PEA_1_P3, optionally at least 80% Preferably, it comprises a second amino acid sequence that is at least 85%, more preferably at least 90%, most preferably at least 95% homologous, said first amino acid sequence and said second amino acid sequence being contiguous and contiguous An isolated chimeric polypeptide encoding M78076_PEA_1_P3 in order.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein M78076_PEA_1_P3 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing the other amino acids, and listing the other amino acids, as shown in Table 690), and the last column is the SNP It is shown whether it is known and the presence of a known SNP in the mutein M78076_PEA_1_P3 sequence supports the putative sequence of this mutein of the invention).

  The glycosylation sites of mutant protein M78076_PEA_1_P3 compared to the known protein amyloid-like protein 1 precursor are shown in Table 691 (showing its position on the amino acid sequence in the first column, the second column has glycosylation sites It indicates whether it is present in the mutein and the last column shows whether this position is different on the mutein).

  The mutein M78076_PEA_1_P3 is encoded by the following transcript: M78076_PEA_1_T2 (sequences shown at the end of the application). The code portion of transcript M78076_PEA_1_T2 is shown in bold, this code portion starts at position 142 and ends at position 1698. The transcript also has the following SNPs listed in Table 692 (showing its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein M78076_PEA_1_P3 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein M78076_PEA_1_P4 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript M78076_PEA_1_T3. An alignment to a known protein (amyloid-like protein 1 precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of the comparison between M78076_PEA_1_P4 and APP1_HUMAN 1. Corresponding to amino acids 1 to 526 of APP1_HUMAN, corresponding to amino acids 1 to 526 of M78076_PEA_1_P4 MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGLCGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPMERWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHT The first amino acid sequence at least 90% homologous to EibuibuijikeibuitiPitiPiaruPitidijibuidiaiwaiefujiemuPijiiaiesuieichiijiefueruarueikeiemudieruiiaruaruemuarukyuaienuibuiemuaruidaburyueiemueidienukyuesukeienueruPikeieidiarukyueieruenuieichiefukyuesuaierukyutieruiikyubuiesujiiarukyuaruerubuiitieichieitiarubuiaieieruaienudikyuaruarueieieruijiefuerueieierukyueidiPiPikyueiiarubuieruerueieruaruaruwaieruarueiikyukeiikyuarueichitieruarueichiwaikyueichibuieieibuidiPiikeieikyukyuemuaruefukyubuieichitieichierukyubuiaiiiarubuienukyuesuerujieruerudikyuenuPieichierueikyuieruaruPikyuaikyuieruerueichiesuieichieruJipiesuieruieipieipijiGSSEDKGGLQPPDSKDDTPMTLPKG, polypeptide few having a sequence corresponding to ECLTVNPSLQIPLNP to amino acid 527-541 of M78076_PEA_1_P4 Said first amino acid sequence comprising a second amino acid sequence of at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous; An isolated chimeric polypeptide encoding M78076_PEA_1_P4, wherein the second amino acid sequence is in contiguous and sequential order.

  2. Of M78076_PEA_1_P4 comprising a polypeptide at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence ECLTVNPSLQIPLNP in M78076_PEA_1_P4 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein M78076_PEA_1_P4 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows SNPs as shown in Table 693) It is shown whether it is known and the presence of a known SNP in the mutein M78076_PEA_1_P4 sequence supports the putative sequence of this mutein of the invention).

  The glycosylation sites of mutant protein M78076_PEA_1_P4 compared to the known protein amyloid-like protein 1 precursor are shown in Table 694 (showing its position on the amino acid sequence in the first column, the second column has glycosylation sites It indicates whether it is present in the mutein and the last column shows whether this position is different on the mutein).

  The mutein M78076_PEA_1_P4 is encoded by the following transcript: M78076_PEA_1_T3 (sequences shown at the end of the application). The code portion of the transcript M78076_PEA_1_T3 is shown in bold, starting from position 142 and ending at position 1764. The transcript also has the following SNPs listed in Table 695 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein M78076_PEA_1_P4 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein M78076_PEA_1_P12 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript M78076_PEA_1_T13. An alignment to a known protein (amyloid-like protein 1 precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of the comparison between M78076_PEA_1_P12 and APP1_HUMAN 1. Corresponding to amino acids 1 to 526 of APP1_HUMAN, corresponding to amino acids 1 to 526 of M78076_PEA_1_P12 MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGLCGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPMERWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSH A first amino acid sequence at least 90% homologous to ErueibuibuijikeibuitiPitiPiaruPitidijibuidiaiwaiefujiemuPijiiaiesuieichiijiefueruarueikeiemudieruiiaruaruemuarukyuaienuibuiemuaruidaburyueiemueidienukyuesukeienueruPikeieidiarukyueieruenuieichiefukyuesuaierukyutieruiikyubuiesujiiarukyuaruerubuiitieichieitiarubuiaieieruaienudikyuaruarueieieruijiefuerueieierukyueidiPiPikyueiiarubuieruerueieruaruaruwaieruarueiikyukeiikyuarueichitieruarueichiwaikyueichibuieieibuidiPiikeieikyukyuemuaruefukyubuieichitieichierukyubuiaiiiarubuienukyuesuerujieruerudikyuenuPieichierueikyuieruaruPikyuaikyuieruerueichiesuieichieruJipiesuieruieipieipijiGSSEDKGGLQPPDSKDDTPMTLPKG, Poripe having a sequence corresponding to ECVCSKGFPFPLIGDSEG to amino acid 527-544 of M78076_PEA_1_P12 Said first amino acid sequence comprising a second amino acid sequence which is at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous to And an isolated chimeric polypeptide encoding M78076_PEA_1_P12, wherein the second amino acid sequence is adjacent and in sequential order.

  2. M78076_PEA_1_P12 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence ECVCSKGFPFPLI GDSEG in M78076_PEA_1_P12 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein M78076_PEA_1_P12 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, enumerating other amino acids, and the last column shows SNPs as shown in Table 696) It indicates whether it is known and the presence of a known SNP in the mutein M78076_PEA_1_P12 sequence supports the predicted sequence of this mutein of the invention).

  The glycosylation sites of the mutated protein M78076_PEA_1_P12 compared to the known protein amyloid-like protein 1 precursor are shown in Table 697 (showing its position on the amino acid sequence in the first column, the second column has glycosylation sites It indicates whether it is present in the mutein and the last column shows whether this position is different on the mutein).

  The mutein M78076_PEA_1_P12 is encoded by the following transcript: M78076_PEA_1_T13 (sequences shown at the end of the application). The code portion of transcript M78076_PEA_1_T13 is shown in bold, this code portion starting at position 142 and ending at position 1773. The transcript also has the following SNPs listed in Table 698 (showing its position on the nucleotide sequence and listing another nucleic acid, the last column shows whether the SNP is known, mutein M78076_PEA_1_P12 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein M78076_PEA_1_P14 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript M78076_PEA_1_T15. An alignment to a known protein (amyloid-like protein 1 precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of the comparison between M78076_PEA_1_P14 and APP1_HUMAN 1. Corresponding to amino acids 1 to 570 of APP1_HUMAN, corresponding to amino acids 1 to 570 of M78076_PEA_1_P14 MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGLCGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPMERWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSH The first amino acid sequence at least 90% homologous to LAVVGKVTPTPRPTDGVDIYFGMPGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQALNEHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQADPPQAERVLLALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQVHTHLQVIEERVNQSLGLLDQNPHLAQELRPQIQELLHSEHLGPSELEAPAPGGSSEDKGGLQPPDSKDDTPMTLPKGSTEQDAASPEKEKMNPLEQYERKVNASVPRGFPFHSSEIQRDEL, M78076_PEA_1_P14 The polypeptide having the sequence VRGGTAGYLGEETRGQRPGCDSQSHTGPSKKPSAPSPLPAGTSWDRGVP corresponding to amino acids 571-619 is at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous An isolated chimeric polypeptide encoding M78076_PEA_1_P14, comprising an amino acid sequence, wherein said first and second amino acid sequences are adjacent and in sequential order.

  2. M78076_PEA_1_P14 comprising a polypeptide that is at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein M78076_PEA_1_P14 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows SNPs as shown in Table 699) It is shown whether it is known and the presence of a known SNP in the mutein M78076_PEA_1_P14 sequence supports the deduced sequence of this mutein of the invention).

  The glycosylation sites of mutant protein M78076_PEA_1_P14 compared to the known protein amyloid-like protein 1 precursor are shown in Table 700 (showing its position on the amino acid sequence in the first column, the second column has glycosylation sites It indicates whether it is present in the mutein and the last column shows whether this position is different on the mutein).

  The mutein M78076_PEA_1_P14 is encoded by the following transcript: M78076_PEA_1_T15 (sequences shown at the end of the application). The coding part of the transcript M78076_PEA_1_T15 is shown in bold, starting from position 142 and ending at position 1998. The transcript also has the following SNPs listed in Table 701 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein M78076_PEA_1_P14 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein M78076_PEA_1_P21 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript M78076_PEA_1_T23. An alignment to a known protein (amyloid-like protein 1 precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of the comparison between M78076_PEA_1_P21 and APP1_HUMAN 1. Corresponding to amino acids 1 to 352 of APP1_HUMAN, corresponding to amino acids 1 to 352 of M78076_PEA_1_P21 MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGLCGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPMERWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSH The first amino acid sequence at least 90% homologous to ErueibuibuijikeibuitiPitiPiaruPitidijibuidiaiwaiefujiemuPijiiaiesuieichiijiefueruarueikeiemudieruiiaruaruemuarukyuaienuiVMREWAMADNQSKNLPKADRQALNE, corresponding to amino acids 406-650 of APP1_HUMAN, corresponding to amino acids 353-597 of M78076_PEA_1_P21 AERVLLALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQVHTHLQVIEERVNQSLGLLDQNPHLAQELRPQIQELLHSEHLGPSELEAPAPGGSSEDKGGLQPPDSKDDTPMTLPKGSTEQDAASPEKEKMNPLEQYERKVNASVPRGFPFHSSEIQRDELAPAGTGVS EAVSGLLIMGAGGGSLIVLSMLLLRRKKPYGAISHGVVEVDPMLTLEEQQLRELQRHGYENPTYRFLEERP and and at least 90% homologous to a second amino acid sequence, the first amino acid sequence and a second amino acid sequence, contiguous and in sequential order, the isolated chimeric polypeptide coding M78076_PEA_1_P21.

  2. Length “n” (wherein n is at least about 10 amino acids long, optionally at least about 20 amino acids long, preferably at least about 30 amino acids long, more preferably at least about 40 amino acids long, most preferably at least about 50 amino acids long, at least two amino acids comprising EA, starting from any of the following structures: amino acids nos. 352-x to 352, amino acids nos. 353 + ((n-2) -x) (formula An isolated chimeric polypeptide encoding an edge portion of M78076_PEA_1_P21, comprising a polypeptide, having a sequence terminating in :), wherein x is a change from 0 to n-2.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: membrane. As for protein localization, both signal peptide estimation programs agree that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has a transmembrane domain downstream of this signal peptide. , Considered a membrane.

  The mutein M78076_PEA_1_P21 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, enumerating other amino acids, and the last column shows SNPs as shown in Table 702) It is shown whether it is known and the presence of a known SNP in the mutein M78076_PEA_1_P21 sequence supports the deduced sequence of this mutein of the invention).

  The glycosylation sites of the mutated protein M78076_PEA_1_P21 compared to the known protein amyloid-like protein 1 precursor are shown in Table 703 (showing its position on the amino acid sequence in the first column, the second column has a glycosylation site It indicates whether it is present in the mutein and the last column shows whether this position is different on the mutein).

  The mutein M78076_PEA_1_P21 is encoded by the following transcript: M78076_PEA_1_T23 (sequences shown at the end of the application). The code portion of transcript M78076_PEA_1_T23 is shown in bold, this code portion starting at position 142 and ending at position 1932. The transcript also has the following SNPs listed in Table 704 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein M78076_PEA_1_P21 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein M78076_PEA_1_P24 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript M78076_PEA_1_T26. An alignment to a known protein (amyloid-like protein 1 precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of the comparison between M78076_PEA_1_P24 and APP1_HUMAN 1. Corresponding to amino acids 1 to 481 of APP1_HUMAN, corresponding to amino acids 1 to 481 of M78076_PEA_1_P24 MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGLCGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPMERWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSH A first amino acid sequence at least 90% homologous to ErueibuibuijikeibuitiPitiPiaruPitidijibuidiaiwaiefujiemuPijiiaiesuieichiijiefueruarueikeiemudieruiiaruaruemuarukyuaienuibuiemuaruidaburyueiemueidienukyuesukeienueruPikeieidiarukyueieruenuieichiefukyuesuaierukyutieruiikyubuiesujiiarukyuaruerubuiitieichieitiarubuiaieieruaienudikyuaruarueieieruijiefuerueieierukyueidiPiPikyueiiarubuieruerueieruaruaruwaieruarueiikyukeiikyuarueichitieruarueichiwaikyueichibuieieibuidiPiikeieikyukyuemuaruefukyubuieichitieichierukyubuiaiEERVNQSLGLLDQNPHLAQELRPQI, polypeptide at least 70% with a sequence corresponding to RECLLPWLPLQISEGRS to amino acid 482-498 of M78076_PEA_1_P24, optionally at least 80%, preferably at least 85%, more Preferred Or M78076_PEA_1_P24, which comprises a second amino acid sequence which is at least 90%, most preferably at least 95% homologous, said first and second amino acid sequences being adjacent and in sequential order Isolated chimeric polypeptide.

  2. M78076_PEA_1_P24 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 90%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence RECLLPWLPLQISEGRS in M78076_PEA_1_P24 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein M78076_PEA_1_P24 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing the other amino acids, and listing the other amino acids, as shown in Table 705), and the last column contains SNPs It is shown whether it is known and the presence of a known SNP in the mutein M78076_PEA_1_P24 sequence supports the putative sequence of this mutein of the invention).

  The glycosylation sites of mutant protein M78076_PEA_1_P24 compared to the known protein amyloid-like protein 1 precursor are shown in Table 706 (showing its position on the amino acid sequence in the first column, the second column has glycosylation sites It indicates whether it is present in the mutein and the last column shows whether this position is different on the mutein).

  The mutein M78076_PEA_1_P24 is encoded by the following transcript: M78076_PEA_1_T26 (sequences shown at the end of the application). The code portion of transcript M78076_PEA_1_T26 is shown in bold, this code portion starting at position 142 and ending at position 1635. The transcript also has the following SNPs listed in Table 707 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein M78076_PEA_1_P24 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein M78076_PEA_1_P2 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript M78076_PEA_1_T27. An alignment to a known protein (amyloid-like protein 1 precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Reporting of the comparison between M78076_PEA_1_P2 and APP1_HUMAN 1. Corresponding to amino acids 1 to 449 of APP1_HUMAN, corresponding to amino acids 1 to 449 of M78076_PEA_1_P2 MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGLCGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPMERWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHT The first amino acid sequence at least 90% homologous to EibuibuijikeibuitiPitiPiaruPitidijibuidiaiwaiefujiemuPijiiaiesuieichiijiefueruarueikeiemudieruiiaruaruemuarukyuaienuibuiemuaruidaburyueiemueidienukyuesukeienueruPikeieidiarukyueieruenuieichiefukyuesuaierukyutieruiikyubuiesujiiarukyuaruerubuiitieichieitiarubuiaieieruaienudikyuaruarueieieruijiefuerueieierukyueidiPiPikyueiiarubuieruerueieruaruaruwaieruarueiikyukeiikyuRHTLRHYQHVAAVDPEKAQQMRFQV, sequence LTSFQLPNAPLFLRRPRLRLFSCPLDPLSVSWTPSYPLNTASLPLPSLSAQLPDPETWTLTCCVFDPCFLALGFLLPPPSILCSVPWIFTAFPRIVFFFFFFLR corresponding to amino acids 450-588 of M78076_PEA_1_P2 Said polypeptide comprising VLALSPRQESSVRSWLIATSTSWVQAILLPQPLE and a second amino acid sequence which is at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous; An isolated chimeric polypeptide encoding M78076_PEA_1_P2, wherein the amino acid sequence of 1 and the second amino acid sequence are adjacent and in sequential order.

  2. At least 70%, at least about 70%, at least 70%, at least 70%, the event is selected as described in the following example. An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: membrane. As for protein localization, both signal peptide estimation programs agree that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has a transmembrane domain downstream of this signal peptide. , Considered a membrane.

  The mutein M78076_PEA_1_P2 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column, as shown in Table 708) It is shown whether it is known and the presence of a known SNP in the mutein M78076_PEA_1_P2 sequence supports the deduced sequence of this mutein of the invention).

  The glycosylation sites of mutant protein M78076_PEA_1_P2 compared to the known protein amyloid-like protein 1 precursor are shown in Table 709 (showing its position on the amino acid sequence in the first column, the second column has glycosylation sites It indicates whether it is present in the mutein and the last column shows whether this position is different on the mutein).

  The mutein M78076_PEA_1_P2 is encoded by the following transcript: M78076_PEA_1_T27 (sequences shown at the end of the application). The code portion of transcript M78076_PEA_1_T27 is shown in bold, this code portion starts at position 142 and ends at position 1905. The transcript also has the following SNPs listed in Table 710 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, the mutein M78076_PEA_1_P2 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein M78076_PEA_1_P25 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript M78076_PEA_1_T28. An alignment to a known protein (amyloid-like protein 1 precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of the comparison between M78076_PEA_1_P25 and APP1_HUMAN 1. Corresponding to amino acids 1 to 448 of APP1_HUMAN, corresponding to amino acids 1 to 448 of M78076_PEA_1_P25 MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGLCGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPMERWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSH The first amino acid sequence at least 90% homologous to ErueibuibuijikeibuitiPitiPiaruPitidijibuidiaiwaiefujiemuPijiiaiesuieichiijiefueruarueikeiemudieruiiaruaruemuarukyuaienuibuiemuaruidaburyueiemueidienukyuesukeienueruPikeieidiarukyueieruenuieichiefukyuesuaierukyutieruiikyubuiesujiiarukyuaruerubuiitieichieitiarubuiaieieruaienudikyuaruarueieieruijiefuerueieierukyueidiPiPikyueiiarubuieruerueieruaruaruwaieruarueiikyukeiiQRHTLRHYQHVAAVDPEKAQQMRFQ, polypeptide at least 70% with a sequence corresponding to PQNPNSQPRAAGSLEVIISHPFVRRLEILISPFQFQNSIPKNSQIVPAASPRGTSSP to amino acid 449-505 of M78076_PEA_1_P25, optionally at least 80%, preferably at least 8 %, More preferably at least 90%, most preferably at least 95%, with a second amino acid sequence, wherein said first and second amino acid sequences are adjacent and in a contiguous order, An isolated chimeric polypeptide encoding M78076_PEA_1_P25.

  2. A sequence comprising at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous polypeptide with MQ An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein M78076_PEA_1_P25 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, enumerating other amino acids, and the last column shows SNPs as shown in Table 711) It is shown whether it is known and the presence of a known SNP in the mutein M78076_PEA_1_P25 sequence supports the putative sequence of this mutein of the invention).

  The glycosylation sites of mutant protein M78076_PEA_1_P25 compared to the known protein amyloid-like protein 1 precursor are shown in Table 712 (showing its position on the amino acid sequence in the first column, the second column has glycosylation sites It indicates whether it is present in the mutein and the last column shows whether this position is different on the mutein).

  The mutein M78076_PEA_1_P25 is encoded by the following transcript: M78076_PEA_1_T28 (sequences shown at the end of the application). The code portion of transcript M78076_PEA_1_T28 is shown in bold, this code portion starting at position 142 and ending at position 1656. The transcript also has the following SNPs listed in Table 713 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein M78076_PEA_1_P25 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  As mentioned above, cluster M78076 is characterized by the 35 segments listed in Table 2 above, the sequence of which is shown at the end of the application. These segments are part of the nucleic acid sequence, which are of particular interest and are individually described herein. A description of each segment of the invention is provided herein.

  The segment cluster M78076_PEA_1_node_0 of the present invention is supported by 47 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M78076_PEA_1_T2, M78076_PEA_1_T3, M78076_PEA_1_T5, M78076_PEA_1_T13, M78076_PEA_1_T15, M78076_PEA_1_T23, M78076_PEA_1_T26, M7J7407C4P Table 714 below describes the start and end positions of this segment on each transcript.

  The segment cluster M78076_PEA_1_node_10 of the present invention is supported by 70 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M78076_PEA_1_T2, M78076_PEA_1_T3, M78076_PEA_1_T5, M78076_PEA_1_T13, M78076_PEA_1_T15, M78076_PEA_1_T23, M78076_PEA_1_T26, M7J7407C4P Table 715 below describes the start and end positions of this segment on each transcript.

  The segment cluster M78076_PEA_1_node_15 of the present invention is supported by 74 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M78076_PEA_1_T2, M78076_PEA_1_T3, M78076_PEA_1_T5, M78076_PEA_1_T13, M78076_PEA_1_T15, M78076_PEA_1_T23, M78076_PEA_1_T26, M7J7407C4P Table 716 below describes the start and end positions of this segment on each transcript.

  The segment cluster M78076_PEA_1_node_18 of the present invention is supported by 95 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M78076_PEA_1_T2, M78076_PEA_1_T3, M78076_PEA_1_T5, M78076_PEA_1_T13, M78076_PEA_1_T15, M78076_PEA_1_T23, M78076_PEA_1_T26, M7J7407C4P Table 717 below describes the start and end positions of this segment on each transcript.

  The segment cluster M78076_PEA_1_node_20 of the present invention is supported by 99 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M78076_PEA_1_T2, M78076_PEA_1_T3, M78076_PEA_1_T5, M78076_PEA_1_T13, M78076_PEA_1_T15, M78076_PEA_1_T23, M78076_PEA_1_T26, M7J7407C4P Table 718 below describes the start and end positions of this segment on each transcript.

  The segment cluster M78076_PEA_1_node_24 of the present invention is supported by 105 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M78076_PEA_1_T2, M78076_PEA_1_T3, M78076_PEA_1_T5, M78076_PEA_1_T13, M78076_PEA_1_T15, M78076_PEA_1_T26, M78076_PEA_1_T27, and M78076. Table 719 below describes the start and end positions of this segment on each transcript.

  The segment cluster M78076_PEA_1_node_26 of the present invention is supported by 99 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M78076_PEA_1_T2, M78076_PEA_1_T3, M78076_PEA_1_T5, M78076_PEA_1_T13, M78076_PEA_1_T15, M78076_PEA_1_T23, M78076_PEA_1_T26, M7J7407C4P Table 720 below describes the start and end positions of this segment on each transcript.

  The segment cluster M78076_PEA_1_node_29 of the present invention is supported by two libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: M78076_PEA_1_T27. Table 721 below describes the start and end positions of this segment on each transcript.

  The segment cluster M78076_PEA_1_node_32 of the present invention is supported by two libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: M78076_PEA_1_T26 and M78076_PEA_1_T27. Table 722 below describes the start and end positions of this segment on each transcript.

  The segment cluster M78076_PEA_1_node_35 of the present invention is supported by 4 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: M78076_PEA_1_T2 and M78076_PEA_1_T5. Table 723 below describes the start and end positions of this segment on each transcript.

  The segment cluster M78076_PEA_1_node_37 of the present invention is supported by 11 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: M78076_PEA_1_T3 and M78076_PEA_1_T5. Table 724 below describes the start and end positions of this segment on each transcript.

  The segment cluster M78076_PEA_1_node_46 of the present invention is supported by three libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: M78076_PEA_1_T15. Table 725 below describes the start and end positions of this segment on each transcript.

  The segment cluster M78076_PEA_1_node_47 of the present invention is supported by 155 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M78076_PEA_1_T2, M78076_PEA_1_T3, M78076_PEA_1_T5, M78076_PEA_1_T13, M78076_PEA_1_T15, and M78076_PEA_1_T23. Table 726 below describes the start and end positions of this segment on each transcript.

  The segment cluster M78076_PEA_1_node_54 of the present invention is supported by 133 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M78076_PEA_1_T2, M78076_PEA_1_T3, M78076_PEA_1_T5, M78076_PEA_1_T13, M78076_PEA_1_T15, M78076_PEA_1_T23, and M78076_PEA_1_T28. Table 727 below describes the start and end positions of this segment on each transcript.

  According to an optional embodiment of the present invention, there is also provided a short segment associated with the above cluster. These segments are up to about 120 bp in length and are therefore included in the individual descriptions.

  The segment cluster M78076_PEA_1_node_1 of the present invention is supported by 47 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M78076_PEA_1_T2, M78076_PEA_1_T3, M78076_PEA_1_T5, M78076_PEA_1_T13, M78076_PEA_1_T15, M78076_PEA_1_T23, M78076_PEA_1_T26, M7J7407C4P Table 728 below describes the start and end positions of this segment on each transcript.

  The segment cluster M78076_PEA_1_node_2 according to the invention can be found in the following transcripts: M78076_PEA_1_T2, M78076_PEA_1_T3, M78076_PEA_1_T5, M78076_PEA_1_T13, M78076_PEA_1_T15. Table 729 below describes the start and end positions of this segment on each transcript.

  The segment cluster M78076_PEA_1_node_3 of the present invention is supported by 52 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M78076_PEA_1_T2, M78076_PEA_1_T3, M78076_PEA_1_T5, M78076_PEA_1_T13, M78076_PEA_1_T15, M78076_PEA_1_T23, M78076_PEA_1_T26, M7J7407C4P Table 730 below lists the start and end positions of this segment on each transcript.

  The segment cluster M78076_PEA_1_node_6 of the present invention is supported by 59 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M78076_PEA_1_T2, M78076_PEA_1_T3, M78076_PEA_1_T5, M78076_PEA_1_T13, M78076_PEA_1_T15, M78076_PEA_1_T23, M78076_PEA_1_T26, M7J7407C4P Table 731 below describes the start and end positions of this segment on each transcript.

  The segment cluster M78076_PEA_1_node_7 of the present invention is supported by 64 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M78076_PEA_1_T2, M78076_PEA_1_T3, M78076_PEA_1_T5, M78076_PEA_1_T13, M78076_PEA_1_T15, M78076_PEA_1_T23, M78076_PEA_1_T26, M7J7407C4P Table 732 below describes the start and end positions of this segment on each transcript.

  The segment cluster M78076_PEA_1_node_12 of the present invention is supported by 71 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M78076_PEA_1_T2, M78076_PEA_1_T3, M78076_PEA_1_T5, M78076_PEA_1_T13, M78076_PEA_1_T15, M78076_PEA_1_T23, M78076_PEA_1_T26, M7J7407C4P Table 733 below describes the start and end positions of this segment on each transcript.

  The segment cluster M78076_PEA_1_node_22 of the present invention is supported by 92 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M78076_PEA_1_T2, M78076_PEA_1_T3, M78076_PEA_1_T5, M78076_PEA_1_T13, M78076_PEA_1_T15, M78076_PEA_1_T23, M78076_PEA_1_T26, M7J7407C4P Table 734 below describes the start and end positions of this segment on each transcript.

  The segment cluster M78076_PEA_1_node_27 according to the invention can be found in the following transcript: M78076_PEA_1_T27. Table 735 below describes the start and end positions of this segment on each transcript.

  The segment cluster M78076_PEA_1_node_30 of the present invention is supported by 90 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M78076_PEA_1_T2, M78076_PEA_1_T3, M78076_PEA_1_T5, M78076_PEA_1_T13, M78076_PEA_1_T15, M78076_PEA_1_T23, M78076_PEA_1_T26, and M7076. Table 736 below describes the start and end positions of this segment on each transcript.

  The segment cluster M78076_PEA_1_node_31 of the present invention is supported by 89 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M78076_PEA_1_T2, M78076_PEA_1_T3, M78076_PEA_1_T5, M78076_PEA_1_T13, M78076_PEA_1_T15, M78076_PEA_1_T23, M78076_PEA_1_T26, and M7076. Table 737 below describes the start and end positions of this segment on each transcript.

  The segment cluster M78076_PEA_1_node_34 of the present invention is supported by 103 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M78076_PEA_1_T2, M78076_PEA_1_T3, M78076_PEA_1_T5, M78076_PEA_1_T13, M78076_PEA_1_T15, and M78076_PEA_1_T23. Table 738 below describes the start and end positions of this segment on each transcript.

  The segment cluster M78076_PEA_1_node_36 according to the invention can be found in the following transcripts: M78076_PEA_1_T2, M78076_PEA_1_T3, M78076_PEA_1_T5, M78076_PEA_1_T13, M78076_PEA_1_T15, and M78076_PEA_1_T23. Table 739 below describes the start and end positions of this segment on each transcript.

  The segment cluster M78076_PEA_1_node_41 according to the invention can be found in the following transcript: M78076_PEA_1_T3 and M78076_PEA_1_T5. Table 740 below describes the start and end positions of this segment on each transcript.

  The segment cluster M78076_PEA_1_node_42 according to the invention can be found in the following transcripts: M78076_PEA_1_T2, M78076_PEA_1_T3, M78076_PEA_1_T5, M78076_PEA_1_T15, and M78076_PEA_1_T23. Table 741 below describes the start and end positions of this segment on each transcript.

  The segment cluster M78076_PEA_1_node_43 of the present invention is supported by 110 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M78076_PEA_1_T2, M78076_PEA_1_T3, M78076_PEA_1_T5, M78076_PEA_1_T15, and M78076_PEA_1_T23. Table 742 below describes the start and end positions of this segment on each transcript.

  Microarray (chip) data for this segment is also available, as follows. As described above, with respect to the clusters themselves, different oligonucleotides were tested for differential expression in different disease states, in particular cancer. The following oligonucleotides were found to reach this segment (for lung cancer) (shown in Table 743).

  The segment cluster M78076_PEA_1_node_45 of the present invention is supported by 132 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M78076_PEA_1_T2, M78076_PEA_1_T3, M78076_PEA_1_T5, M78076_PEA_1_T13, M78076_PEA_1_T15, and M78076_PEA_1_T23. Table 744 below describes the start and end positions of this segment on each transcript.

  Microarray (chip) data for this segment is also available, as follows. As described above, with respect to the clusters themselves, different oligonucleotides were tested for differential expression in different disease states, in particular cancer. The following oligonucleotides were found to reach this segment (for lung cancer) (shown in Table 745).

  The segment cluster M78076_PEA_1_node_49 of the present invention is supported by 129 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M78076_PEA_1_T2, M78076_PEA_1_T3, M78076_PEA_1_T5, M78076_PEA_1_T13, M78076_PEA_1_T15, and M78076_PEA_1_T23. Table 746 below describes the start and end positions of this segment on each transcript.

  The segment cluster M78076_PEA_1_node_50 of the present invention is supported by 125 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M78076_PEA_1_T2, M78076_PEA_1_T3, M78076_PEA_1_T5, M78076_PEA_1_T13, M78076_PEA_1_T15, and M78076_PEA_1_T23. Table 747 below describes the start and end positions of this segment on each transcript.

  The segment cluster M78076_PEA_1_node_51 of the present invention is supported by 123 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: M78076_PEA_1_T2, M78076_PEA_1_T3, M78076_PEA_1_T5, M78076_PEA_1_T13, M78076_PEA_1_T15, and M78076_PEA_1_T23. Table 748 below describes the start and end positions of this segment on each transcript.

  The segment cluster M78076_PEA_1_node_52 according to the invention can be found in the following transcripts: M78076_PEA_1_T2, M78076_PEA_1_T3, M78076_PEA_1_T5, M78076_PEA_1_T13, M78076_PEA_1_T15, and M78076_PEA_1_T23. Table 749 below describes the start and end positions of this segment on each transcript.

  The segment cluster M78076_PEA_1_node_53 according to the invention can be found in the following transcripts: M78076_PEA_1_T2, M78076_PEA_1_T3, M78076_PEA_1_T5, M78076_PEA_1_T13, M78076_PEA_1_T15, M78076_PEA_1_TPE. Table 750 below describes the start and end positions of this segment on each transcript.

Mutated protein alignment against previously known proteins:
Sequence name: APP1_HUMAN

Sequence documentation:

Alignment of: M78076_PEA_1_P3 x APP1_HUMAN ..

Alignment segment 1/1:

Quality: 5132.00 Escore: 0
Matching length: 517 Total length: 517
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MGPASPAARGSRRPRPQPPLPLPLLLLLLLRAQPAIGSLAGGPSGAAEA 50
||||||||||||||||||||||||||||||||||||||||
1 MGPASPAARGSRRPRPQPPLPLPLLLLLLLRAQPAIGSLAGGPSGAAEA 50
....
51 PGSAQVAGLCGRLTLHRDLRTGRWEPDPQ RSRRCLRDPQRVLEYCRQMYP 100
||||||||||||||||||||||||||||||||||||||||
51 PGSAQVAGLCGRLTLHRDLRTGRWEPDPQ RSRRCLRDPQRVLEYCRQMYP 100
....
101 ELQ IARVEQ ATQAIPMERWCGGSRSGSCAHPHHQV VPFRCLPGEFSEAL 150
||||||||||||||||||||||||||||||||||||||||
101 ELQ IARVEQ ATQAIPMERWCGGSRSGSCAHPHHQV VPFRCLPGEFSEAL 150
....
151 LVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSD 200
||||||||||||||||||||||||||||||||||||||||
151 LVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSD 200
....
201 RFRGVEYVCCPPPGTPPTSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFP 250
||||||||||||||||||||||||||||||||||||||||
201 RFRGVEYVCCPPPGTPPTSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFP 250
....
251 QPVDDYFVEPPQAEEEEETVPPPSSHTLASVVGKVTPTPRPDGMDIYFGM 300
||||||||||||||||||||||||||||||||||||||||
251 QPVDDYFVEPPQAEEEEETVPPPSSHTLASVVGKVTPTPRPDGMDIYFGM 300
....
301 PGEISEHEGFLAKMDLEERRMRQINEVMREWA AMDNQSKNLPKADRQAL 350
||||||||||||||||||||||||||||||||||||||||
301 PGEISEHEGFLAKMDLEERRMRQINEVMREWA AMDNQSKNLPKADRQAL 350
....
351 NEHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLA ALQ 400
||||||||||||||||||||||||||||||||||||||||
351 NEHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLA ALQ 400
....
401 ADPPQAERVLLALLRRYLRAEQKEQRHTHRHYQHVAAVDPEKAQQMRFQVH 450
||||||||||||||||||||||||||||||||||||||||
401 ADPPQAERVLLALLRRYLRAEQKEQRHTHRHYQHVAAVDPEKAQQMRFQVH 450
....
451 THLQVIEERBN QSLGLLDQ NPHLA QELRPQIQELLHSEHLGPSELAPAP 500
||||||||||||||||||||||||||||||||||||||||
451 THLQVIEERBN QSLGLLDQ NPHLA QELRPQIQELLHSEHLGPSELAPAP 500
.
501 GGSSEDKGGLQPPDSKD 517
||||||||||||||||
501 GGSSEDKGGLQPPDSKD 517






Sequence name: APP1_HUMAN

Sequence documentation:

Alignment of: M78076_PEA_1_P4 x APP1_HUMAN ..

Alignment segment 1/1:

Quality: 5223.00 Escore: 0
Matching length: 526 Total length: 526
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MGPASPAARGSRRPRPQPPLPLPLLLLLLLRAQPAIGSLAGGPSGAAEA 50
||||||||||||||||||||||||||||||||||||||||
1 MGPASPAARGSRRPRPQPPLPLPLLLLLLLRAQPAIGSLAGGPSGAAEA 50
....
51 PGSAQVAGLCGRLTLHRDLRTGRWEPDPQ RSRRCLRDPQRVLEYCRQMYP 100
||||||||||||||||||||||||||||||||||||||||
51 PGSAQVAGLCGRLTLHRDLRTGRWEPDPQ RSRRCLRDPQRVLEYCRQMYP 100
....
101 ELQ IARVEQ ATQAIPMERWCGGSRSGSCAHPHHQV VPFRCLPGEFSEAL 150
||||||||||||||||||||||||||||||||||||||||
101 ELQ IARVEQ ATQAIPMERWCGGSRSGSCAHPHHQV VPFRCLPGEFSEAL 150
....
151 LVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSD 200
||||||||||||||||||||||||||||||||||||||||
151 LVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSD 200
....
201 RFRGVEYVCCPPPGTPPTSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFP 250
||||||||||||||||||||||||||||||||||||||||
201 RFRGVEYVCCPPPGTPPTSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFP 250
....
251 QPVDDYFVEPPQAEEEEETVPPPSSHTLASVVGKVTPTPRPDGMDIYFGM 300
||||||||||||||||||||||||||||||||||||||||
251 QPVDDYFVEPPQAEEEEETVPPPSSHTLASVVGKVTPTPRPDGMDIYFGM 300
....
301 PGEISEHEGFLAKMDLEERRMRQINEVMREWA AMDNQSKNLPKADRQAL 350
||||||||||||||||||||||||||||||||||||||||
301 PGEISEHEGFLAKMDLEERRMRQINEVMREWA AMDNQSKNLPKADRQAL 350
....
351 NEHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLA ALQ 400
||||||||||||||||||||||||||||||||||||||||
351 NEHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLA ALQ 400
....
401 ADPPQAERVLLALLRRYLRAEQKEQRHTHRHYQHVAAVDPEKAQQMRFQVH 450
||||||||||||||||||||||||||||||||||||||||
401 ADPPQAERVLLALLRRYLRAEQKEQRHTHRHYQHVAAVDPEKAQQMRFQVH 450
....
451 THLQVIEERBN QSLGLLDQ NPHLA QELRPQIQELLHSEHLGPSELAPAP 500
||||||||||||||||||||||||||||||||||||||||
451 THLQVIEERBN QSLGLLDQ NPHLA QELRPQIQELLHSEHLGPSELAPAP 500
.
501 GGSSEDKGGLQPPDSK DDTPMTLPKG 526
||||||||||||||||||||||||
501 GGSSEDKGGLQPPDSK DDTPMTLPKG 526






Sequence name: APP1_HUMAN

Sequence documentation:

Alignment of: M78076_PEA_1_P12 x APP1_HUMAN ..

Alignment segment 1/1:

Quality: 5223.00 Escore: 0
Matching length: 526 Total length: 526
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MGPASPAARGSRRPRPQPPLPLPLLLLLLLRAQPAIGSLAGGPSGAAEA 50
||||||||||||||||||||||||||||||||||||||||
1 MGPASPAARGSRRPRPQPPLPLPLLLLLLLRAQPAIGSLAGGPSGAAEA 50
....
51 PGSAQVAGLCGRLTLHRDLRTGRWEPDPQ RSRRCLRDPQRVLEYCRQMYP 100
||||||||||||||||||||||||||||||||||||||||
51 PGSAQVAGLCGRLTLHRDLRTGRWEPDPQ RSRRCLRDPQRVLEYCRQMYP 100
....
101 ELQ IARVEQ ATQAIPMERWCGGSRSGSCAHPHHQV VPFRCLPGEFSEAL 150
||||||||||||||||||||||||||||||||||||||||
101 ELQ IARVEQ ATQAIPMERWCGGSRSGSCAHPHHQV VPFRCLPGEFSEAL 150
....
151 LVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSD 200
||||||||||||||||||||||||||||||||||||||||
151 LVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSD 200
....
201 RFRGVEYVCCPPPGTPPTSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFP 250
||||||||||||||||||||||||||||||||||||||||
201 RFRGVEYVCCPPPGTPPTSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFP 250
....
251 QPVDDYFVEPPQAEEEEETVPPPSSHTLASVVGKVTPTPRPDGMDIYFGM 300
||||||||||||||||||||||||||||||||||||||||
251 QPVDDYFVEPPQAEEEEETVPPPSSHTLASVVGKVTPTPRPDGMDIYFGM 300
....
301 PGEISEHEGFLAKMDLEERRMRQINEVMREWA AMDNQSKNLPKADRQAL 350
||||||||||||||||||||||||||||||||||||||||
301 PGEISEHEGFLAKMDLEERRMRQINEVMREWA AMDNQSKNLPKADRQAL 350
....
351 NEHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLA ALQ 400
||||||||||||||||||||||||||||||||||||||||
351 NEHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLA ALQ 400
....
401 ADPPQAERVLLALLRRYLRAEQKEQRHTHRHYQHVAAVDPEKAQQMRFQVH 450
||||||||||||||||||||||||||||||||||||||||
401 ADPPQAERVLLALLRRYLRAEQKEQRHTHRHYQHVAAVDPEKAQQMRFQVH 450
....
451 THLQVIEERBN QSLGLLDQ NPHLA QELRPQIQELLHSEHLGPSELAPAP 500
||||||||||||||||||||||||||||||||||||||||
451 THLQVIEERBN QSLGLLDQ NPHLA QELRPQIQELLHSEHLGPSELAPAP 500
.
501 GGSSEDKGGLQPPDSK DDTPMTLPKG 526
||||||||||||||||||||||||
501 GGSSEDKGGLQPPDSK DDTPMTLPKG 526






Sequence name: APP1_HUMAN

Sequence documentation:

Alignment of: M78076_PEA_1_P14 x APP1_HUMAN ..

Alignment segment 1/1:

Quality: 5672.00 Escore: 0
Matching length: 575 Total length: 575
Matching Percent Similarity: 99.48 Matching Percent Identity: 99.48
Total Percent Similarity: 99.48 Total Percent Identity: 99.48
Gaps: 0

Alignment:
....
1 MGPASPAARGSRRPRPQPPLPLPLLLLLLLRAQPAIGSLAGGPSGAAEA 50
||||||||||||||||||||||||||||||||||||||||
1 MGPASPAARGSRRPRPQPPLPLPLLLLLLLRAQPAIGSLAGGPSGAAEA 50
....
51 PGSAQVAGLCGRLTLHRDLRTGRWEPDPQ RSRRCLRDPQRVLEYCRQMYP 100
||||||||||||||||||||||||||||||||||||||||
51 PGSAQVAGLCGRLTLHRDLRTGRWEPDPQ RSRRCLRDPQRVLEYCRQMYP 100
....
101 ELQ IARVEQ ATQAIPMERWCGGSRSGSCAHPHHQV VPFRCLPGEFSEAL 150
||||||||||||||||||||||||||||||||||||||||
101 ELQ IARVEQ ATQAIPMERWCGGSRSGSCAHPHHQV VPFRCLPGEFSEAL 150
....
151 LVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSD 200
||||||||||||||||||||||||||||||||||||||||
151 LVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSD 200
....
201 RFRGVEYVCCPPPGTPPTSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFP 250
||||||||||||||||||||||||||||||||||||||||
201 RFRGVEYVCCPPPGTPPTSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFP 250
....
251 QPVDDYFVEPPQAEEEEETVPPPSSHTLASVVGKVTPTPRPDGMDIYFGM 300
||||||||||||||||||||||||||||||||||||||||
251 QPVDDYFVEPPQAEEEEETVPPPSSHTLASVVGKVTPTPRPDGMDIYFGM 300
....
301 PGEISEHEGFLAKMDLEERRMRQINEVMREWA AMDNQSKNLPKADRQAL 350
||||||||||||||||||||||||||||||||||||||||
301 PGEISEHEGFLAKMDLEERRMRQINEVMREWA AMDNQSKNLPKADRQAL 350
....
351 NEHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLA ALQ 400
||||||||||||||||||||||||||||||||||||||||
351 NEHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLA ALQ 400
....
401 ADPPQAERVLLALLRRYLRAEQKEQRHTHRHYQHVAAVDPEKAQQMRFQVH 450
||||||||||||||||||||||||||||||||||||||||
401 ADPPQAERVLLALLRRYLRAEQKEQRHTHRHYQHVAAVDPEKAQQMRFQVH 450
....
451 THLQVIEERBN QSLGLLDQ NPHLA QELRPQIQELLHSEHLGPSELAPAP 500
||||||||||||||||||||||||||||||||||||||||
451 THLQVIEERBN QSLGLLDQ NPHLA QELRPQIQELLHSEHLGPSELAPAP 500
....
501 GGSSEDKGGLQPPDSKDDTMPTLPGGSTEQDA ASPEKEK MNPLEQYERKV 550
||||||||||||||||||||||||||||||||||||||||
501 GGSSEDKGGLQPPDSKDDTMPTLPGGSTEQDA ASPEKEK MNPLEQYERKV 550
.
551 NASVPRGFPFHSSEIQRDELVRGT 575
||||||||||||||||||||
551 NASVPRGFPFHSSEIQRDELAPAGT 575






Sequence name: APP1_HUMAN

Sequence documentation:

Alignment of: M78076_PEA_1_P21 x APP1_HUMAN ..

Alignment segment 1/1:

Quality: 5822.00 Escore: 0
Matching length: 597 Total length: 650
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 91.85 Total Percent Identity: 91.85
Gaps: 1

Alignment:
....
1 MGPASPAARGSRRPRPQPPLPLPLLLLLLLRAQPAIGSLAGGPSGAAEA 50
||||||||||||||||||||||||||||||||||||||||
1 MGPASPAARGSRRPRPQPPLPLPLLLLLLLRAQPAIGSLAGGPSGAAEA 50
....
51 PGSAQVAGLCGRLTLHRDLRTGRWEPDPQ RSRRCLRDPQRVLEYCRQMYP 100
||||||||||||||||||||||||||||||||||||||||
51 PGSAQVAGLCGRLTLHRDLRTGRWEPDPQ RSRRCLRDPQRVLEYCRQMYP 100
....
101 ELQ IARVEQ ATQAIPMERWCGGSRSGSCAHPHHQV VPFRCLPGEFSEAL 150
||||||||||||||||||||||||||||||||||||||||
101 ELQ IARVEQ ATQAIPMERWCGGSRSGSCAHPHHQV VPFRCLPGEFSEAL 150
....
151 LVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSD 200
||||||||||||||||||||||||||||||||||||||||
151 LVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSD 200
....
201 RFRGVEYVCCPPPGTPPTSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFP 250
||||||||||||||||||||||||||||||||||||||||
201 RFRGVEYVCCPPPGTPPTSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFP 250
....
251 QPVDDYFVEPPQAEEEEETVPPPSSHTLASVVGKVTPTPRPDGMDIYFGM 300
||||||||||||||||||||||||||||||||||||||||
251 QPVDDYFVEPPQAEEEEETVPPPSSHTLASVVGKVTPTPRPDGMDIYFGM 300
....
301 PGEISEHEGFLAKMDLEERRMRQINEVMREWA AMDNQSKNLPKADRQAL 350
||||||||||||||||||||||||||||||||||||||||
301 PGEISEHEGFLAKMDLEERRMRQINEVMREWA AMDNQSKNLPKADRQAL 350
....
351 NE .................................................. 352
||
351 NEHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLA ALQ 400
....
353 ..... AERVLLALRRYLRAEQKEQRHTHRHYQHVAAVDPEKAQQMRFQVH 397
|||||||||||||||||||||||||||||||||||||||
401 ADPPQAERVLLALLRRYLRAEQKEQRHTHRHYQHVAAVDPEKAQQMRFQVH 450
....
398 THLQVIEERBN QSLGLLDQ NPHLA QELRPQIQELLHSEHLGPSELAPAP 447
||||||||||||||||||||||||||||||||||||||||
451 THLQVIEERBN QSLGLLDQ NPHLA QELRPQIQELLHSEHLGPSELAPAP 500
....
448 GGSSEDDKGGLQPPDSKDDTMPTLPGGSTEQDA ASPEKEK MNPLEQYERKV 497
||||||||||||||||||||||||||||||||||||||||
501 GGSSEDKGGLQPPDSKDDTMPTLPGGSTEQDA ASPEKEK MNPLEQYERKV 550
....
498 NASVPRGFPFHSEIQRDELAPAGTGVSREAVSGLLIMGAGGGSLISLSM 547
||||||||||||||||||||||||||||||||||||||||
551 NASVPRGFPFHSEIQRDELAPAGTGVSREAVSGLLIMGAGGGSLISLSM 600
....
548 LLLRRKKPYGAISHGVVEVDPMLTLEEQQLRELQRHGYENPTYRFLEERP 597
||||||||||||||||||||||||||||||||||||||||
601 LLLRRKKPYGAISHGVVEVDPMLTLEEQQLRELQRHGYENPTYRFLEERP 650






Sequence name: APP1_HUMAN

Sequence documentation:

Alignment of: M78076_PEA_1_P24 x APP1_HUMAN ..

Alignment segment 1/1:

Quality: 4791.00 Escore: 0
Matching length: 485 Total length: 485
Matching Percent Similarity: 99.79 Matching Percent Identity: 99.59
Total Percent Similarity: 99.79 Total Percent Identity: 99.59
Gaps: 0

Alignment:
....
1 MGPASPAARGSRRPRPQPPLPLPLLLLLLLRAQPAIGSLAGGPSGAAEA 50
||||||||||||||||||||||||||||||||||||||||
1 MGPASPAARGSRRPRPQPPLPLPLLLLLLLRAQPAIGSLAGGPSGAAEA 50
....
51 PGSAQVAGLCGRLTLHRDLRTGRWEPDPQ RSRRCLRDPQRVLEYCRQMYP 100
||||||||||||||||||||||||||||||||||||||||
51 PGSAQVAGLCGRLTLHRDLRTGRWEPDPQ RSRRCLRDPQRVLEYCRQMYP 100
....
101 ELQ IARVEQ ATQAIPMERWCGGSRSGSCAHPHHQV VPFRCLPGEFSEAL 150
||||||||||||||||||||||||||||||||||||||||
101 ELQ IARVEQ ATQAIPMERWCGGSRSGSCAHPHHQV VPFRCLPGEFSEAL 150
....
151 LVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSD 200
||||||||||||||||||||||||||||||||||||||||
151 LVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSD 200
....
201 RFRGVEYVCCPPPGTPPTSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFP 250
||||||||||||||||||||||||||||||||||||||||
201 RFRGVEYVCCPPPGTPPTSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFP 250
....
251 QPVDDYFVEPPQAEEEEETVPPPSSHTLASVVGKVTPTPRPDGMDIYFGM 300
||||||||||||||||||||||||||||||||||||||||
251 QPVDDYFVEPPQAEEEEETVPPPSSHTLASVVGKVTPTPRPDGMDIYFGM 300
....
301 PGEISEHEGFLAKMDLEERRMRQINEVMREWA AMDNQSKNLPKADRQAL 350
||||||||||||||||||||||||||||||||||||||||
301 PGEISEHEGFLAKMDLEERRMRQINEVMREWA AMDNQSKNLPKADRQAL 350
....
351 NEHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLA ALQ 400
||||||||||||||||||||||||||||||||||||||||
351 NEHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLA ALQ 400
....
401 ADPPQAERVLLALLRRYLRAEQKEQRHTHRHYQHVAAVDPEKAQQMRFQVH 450
||||||||||||||||||||||||||||||||||||||||
401 ADPPQAERVLLALLRRYLRAEQKEQRHTHRHYQHVAAVDPEKAQQMRFQVH 450
....
451 THLQVIEERVNQSLGLLDQNPHLAQELRPQIRECL 485
||||||||||||||||||||||||||||: |
451 THLQVIEERBN QSLGLLDQ NPHLA QELRPQIQELL 485






Sequence name: APP1_HUMAN

Sequence documentation:

Alignment of: M78076_PEA_1_P2 x APP1_HUMAN ..

Alignment segment 1/1:

Quality: 4474.00 Escore: 0
Matching length: 454 Total length: 454
Matching Percent Similarity: 99.56 Matching Percent Identity: 99.34
Total Percent Similarity: 99.56 Total Percent Identity: 99.34
Gaps: 0

Alignment:
....
1 MGPASPAARGSRRPRPQPPLPLPLLLLLLLRAQPAIGSLAGGPSGAAEA 50
||||||||||||||||||||||||||||||||||||||||
1 MGPASPAARGSRRPRPQPPLPLPLLLLLLLRAQPAIGSLAGGPSGAAEA 50
....
51 PGSAQVAGLCGRLTLHRDLRTGRWEPDPQ RSRRCLRDPQRVLEYCRQMYP 100
||||||||||||||||||||||||||||||||||||||||
51 PGSAQVAGLCGRLTLHRDLRTGRWEPDPQ RSRRCLRDPQRVLEYCRQMYP 100
....
101 ELQ IARVEQ ATQAIPMERWCGGSRSGSCAHPHHQV VPFRCLPGEFSEAL 150
||||||||||||||||||||||||||||||||||||||||
101 ELQ IARVEQ ATQAIPMERWCGGSRSGSCAHPHHQV VPFRCLPGEFSEAL 150
....
151 LVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSD 200
||||||||||||||||||||||||||||||||||||||||
151 LVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSD 200
....
201 RFRGVEYVCCPPPGTPPTSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFP 250
||||||||||||||||||||||||||||||||||||||||
201 RFRGVEYVCCPPPGTPPTSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFP 250
....
251 QPVDDYFVEPPQAEEEEETVPPPSSHTLASVVGKVTPTPRPDGMDIYFGM 300
||||||||||||||||||||||||||||||||||||||||
251 QPVDDYFVEPPQAEEEEETVPPPSSHTLASVVGKVTPTPRPDGMDIYFGM 300
....
301 PGEISEHEGFLAKMDLEERRMRQINEVMREWA AMDNQSKNLPKADRQAL 350
||||||||||||||||||||||||||||||||||||||||
301 PGEISEHEGFLAKMDLEERRMRQINEVMREWA AMDNQSKNLPKADRQAL 350
....
351 NEHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLA ALQ 400
||||||||||||||||||||||||||||||||||||||||
351 NEHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLA ALQ 400
....
401 ADPPQAERVLLALLRRYLRAEQKEQRHTHRHYQHVAAVDPEKAQQMRFQVL 450
||||||||||||||||||||||||||||||||||||||||
401 ADPPQAERVLLALLRRYLRAEQKEQRHTHRHYQHVAAVDPEKAQQMRFQVH 450

451 TSFQ 454
|: |
451 THLQ 454







Sequence name: APP1_HUMAN

Sequence documentation:

Alignment of: M78076_PEA_1_P25 x APP1_HUMAN ..

Alignment segment 1/1:

Quality: 4455.00 Escore: 0
Matching length: 448 Total length: 448
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MGPASPAARGSRRPRPQPPLPLPLLLLLLLRAQPAIGSLAGGPSGAAEA 50
||||||||||||||||||||||||||||||||||||||||
1 MGPASPAARGSRRPRPQPPLPLPLLLLLLLRAQPAIGSLAGGPSGAAEA 50
....
51 PGSAQVAGLCGRLTLHRDLRTGRWEPDPQ RSRRCLRDPQRVLEYCRQMYP 100
||||||||||||||||||||||||||||||||||||||||
51 PGSAQVAGLCGRLTLHRDLRTGRWEPDPQ RSRRCLRDPQRVLEYCRQMYP 100
....
101 ELQ IARVEQ ATQAIPMERWCGGSRSGSCAHPHHQV VPFRCLPGEFSEAL 150
||||||||||||||||||||||||||||||||||||||||
101 ELQ IARVEQ ATQAIPMERWCGGSRSGSCAHPHHQV VPFRCLPGEFSEAL 150
....
151 LVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSD 200
||||||||||||||||||||||||||||||||||||||||
151 LVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSD 200
....
201 RFRGVEYVCCPPPGTPPTSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFP 250
||||||||||||||||||||||||||||||||||||||||
201 RFRGVEYVCCPPPGTPPTSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFP 250
....
251 QPVDDYFVEPPQAEEEEETVPPPSSHTLASVVGKVTPTPRPDGMDIYFGM 300
||||||||||||||||||||||||||||||||||||||||
251 QPVDDYFVEPPQAEEEEETVPPPSSHTLASVVGKVTPTPRPDGMDIYFGM 300
....
301 PGEISEHEGFLAKMDLEERRMRQINEVMREWA AMDNQSKNLPKADRQAL 350
||||||||||||||||||||||||||||||||||||||||
301 PGEISEHEGFLAKMDLEERRMRQINEVMREWA AMDNQSKNLPKADRQAL 350
....
351 NEHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLA ALQ 400
||||||||||||||||||||||||||||||||||||||||
351 NEHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLA ALQ 400
....
401 ADPPQAERVLLALRRYLRAEQKEQRHTHRHYQHVAAVDPEKAQQMRFQ 448
|||||||||||||||||||||||||||||||||||||||
401 ADPPQAERVLLALRRYLRAEQKEQRHTHRHYQHVAAVDPEKAQQMRFQ 448

Description of cluster T99080 Cluster T99080 is characterized by 14 transcripts and 11 segments of interest, the names of which are shown in Tables 751 and 752 respectively, and the sequence itself is shown at the end of the application. Selected protein variants are shown in Table 753.

  These sequences are known as acylphosphatase organ common-type isoenzymes (SwissProt accession identifier ACYO_HUMAN, synonym EC 3.6.1.7, acylphosphatase phosphohydrolase), which is a known protein, previously known herein as a protein , A variant form of the acyl phosphatase erythrocyte isoenzyme (SEQ ID NO: 1440).

  The sequence of the protein acyl phosphatase organ common isoenzyme is shown at the end of the application as "acyl phosphatase organ common isoenzyme amino acid sequence". Known polymorphisms of this sequence are shown in Table 754.

  The following GO annotation applies to previously known proteins. The following annotations have been found: phosphate metabolism, which is an annotation related to biological processes, and acyl phosphatase, which is an annotation related to molecular function.

  GO assignments can be made at one or more http: // www. expasy. SwissProt / TremBl Protein knowledgebase available from ch / sprot / or http: // www. ncbi. nlm. nih. Depends on Locuslink available from gov / projects / LocusLink /.

  As mentioned above, cluster T99080 features the 14 transcripts listed in Table 1 above. These transcripts encode a protein which is a variant of the protein acyl phosphatase organotypic isoenzyme. A description of each mutein of the invention is provided herein.

  The mutein T99080_PEA_4_P1 according to the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript T99080_PEA_1_T0. The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein T99080_PEA_4_P1 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows SNPs as shown in Table 755) It indicates whether it is known and the presence of a known SNP in the mutein T99080_PEA_4_P1 sequence supports the putative sequence of this mutein of the invention).

  The mutein T99080_PEA_4_P1 is encoded by the following transcript: T99080_PEA_4_T0 (sequences shown at the end of the application). The code portion of the transcript T99080_PEA_4_T0 is shown in bold, starting from position 226 and ending at position 411. The transcript also has the following SNPs listed in Table 756 (showing its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein T99080_PEA_4_P1 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein T99080_PEA_4_P2 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript T99080_PEA_4_T2. The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: membrane. Although protein localization is a partial protein, it is considered to be a membrane because both transmembrane domain estimation programs presume that this protein has a transmembrane domain.

  The mutein T99080_PEA_4_P2 is encoded by the following transcript: T99080_PEA_4_T2 (sequences shown at the end of the application). The code portion of the transcript T99080_PEA_4_T2 is shown in bold, starting from position 1 and ending at position 192. The transcript also has the following SNPs listed in Table 757 (showing its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein T99080_PEA_4_P2 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein T99080_PEA_4_P5 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript T99080_PEA_4_T6. An alignment to a known protein (acyl phosphatase common organ isoenzyme) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report on comparison between T99080_PEA_4_P5 and ACYO_HUMAN_V1 (SEQ ID NO: 1441) At least 70%, optionally at least 80%, preferably at least 85%, preferably at least 90%, more preferably at least 90%, most preferably at least 95% homologous to a polypeptide having the sequence MPASARAGAGLLLAFLRALGCAGRAPGLS corresponding to amino acids 1-30 of T99080_PEA_4_P5 The amino acid sequence of 1 and amino acid 1 to 99 of ACYO_HUMAN_V1 and corresponding to amino acid 31 to 129 of T99080_PEA_4_P5 are also used. Wherein the door, the first amino acid sequence and a second amino acid sequence, contiguous and in sequential order, the isolated chimeric polypeptide coding T99080_PEA_4_P5.

  2. The tip of T99080_PEA_4_P5 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence MPASARALAGAGLLLAFLRALGCAGRAPGLS of T99080_PEA_4_P5 An isolated polypeptide encoding

  It should be noted that the known protein sequence (ACYO_HUMAN) has one or more changes from the sequence shown at the end of the application and this amino acid sequence is named ACYO_HUMAN_V1. The occurrence of these changes was previously known and listed in the following table.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein T99080_PEA_4_P5 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, enumerating other amino acids, and the last column shows SNPs as shown in Table 759) It indicates whether it is known and the presence of a known SNP in the mutein T99080_PEA_4_P5 sequence supports the putative sequence of this mutein of the invention).

  The mutein T99080_PEA_4_P5 is encoded by the following transcript: T99080_PEA_4_T6 (sequences shown at the end of the application). The code portion of transcript T99080_PEA_4_T6 is shown in bold, starting from position 226 and ending at position 612. The transcript also has the following SNPs listed in Table 760 (indicating its position on the nucleotide sequence and listing another nucleic acid, the last column indicating whether the SNP is known, mutein T99080_PEA_4_P5 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein T99080_PEA_4_P8 according to the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript T99080_PEA_4_T9. An alignment to a known protein (acyl phosphatase common organ isoenzyme) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between T99080_PEA_4_P8 and ACYO_HUMAN_V1 1. A polypeptide having a sequence M corresponding to amino acids 1 to 1 of T99080_PEA_4_P8 at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous QAEGKKLGLVGWVQNTDRGTVQQQLQPISKVRHMQEWLETRGSPKSHIDKANFEKEKILNKLDYSDFQIV corresponding to amino acid 28 to 99 of ACYO_HUMAN_V1 and also to amino acid 2 to 73 of T99080_PEA_4_P8 T99080_PEA_, where the two amino acid sequences are in contiguous and sequential order Isolated chimeric polypeptide encoding _P8.

  It should be noted that the known protein sequence (ACYO_HUMAN) has one or more changes from the sequence shown at the end of the application and this amino acid sequence is named ACYO_HUMAN_V1. The occurrence of these changes was previously known and listed in the following table.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: Intracellular. Protein localization is considered to be intracellular as no transmembrane domain estimation program will deduce that this protein is a transmembrane domain. Furthermore, both signal peptide deducing programs deduce that this protein is a non-secretory protein.

  The mutein T99080_PEA_4_P8 is encoded by the following transcript: T99080_PEA_4_T9 (sequences shown at the end of the application). The code portion of the transcript T99080_PEA_4_T9 is shown in bold, starting from position 162 and ending at position 380. The transcript also has the following SNPs listed in Table 762 (showing its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein T99080_PEA_4_P8 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein T99080_PEA_4_P9 according to the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript T99080_PEA_1_T10. The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: membrane. Although protein localization is a partial protein, it is considered to be a membrane because both transmembrane domain estimation programs presume that this protein has a transmembrane domain.

  The mutein T99080_PEA_4_P9 is encoded by the following transcript: T99080_PEA_4_T10 (sequences shown at the end of the application). The code part of the transcript T99080_PEA_4_T10 is shown in bold, this code part starts from position 1 and ends at position 261. The transcript also has the following SNPs listed in Table 763 (showing its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein T99080_PEA_4_P9 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein T99080_PEA_4_P10 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript T99080_PEA_1_T11. The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: membrane. Although protein localization is a partial protein, it is considered to be a membrane because both transmembrane domain estimation programs presume that this protein has a transmembrane domain.

  The mutein T99080_PEA_4_P10 is encoded by the following transcript: T99080_PEA_4_T11 (sequences shown at the end of the application). The code portion of the transcript T99080_PEA_4_T11 is shown in bold, starting from position 1 and ending at position 240. The transcript also has the following SNPs listed in Table 764 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein T99080_PEA_4_P10 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein T99080_PEA_4_P12 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript T99080_PEA_1_T14. The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: membrane. Although protein localization is a partial protein, it is considered to be a membrane because both transmembrane domain estimation programs presume that this protein has a transmembrane domain.

  The mutein T99080_PEA_4_P12 is encoded by the following transcript: T99080_PEA_4_T14 (sequences shown at the end of the application). The code portion of the transcript T99080_PEA_4_T14 is shown in bold, starting from position 1 and ending at position 282.

  The mutein T99080_PEA_4_P13 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript T99080_PEA_1_T17. The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: membrane. Although protein localization is a partial protein, it is considered to be a membrane because both transmembrane domain estimation programs presume that this protein has a transmembrane domain.

  The mutein T99080_PEA_4_P13 is encoded by the following transcript: T99080_PEA_4_T17 (sequences shown at the end of the application). The code portion of the transcript T99080_PEA_4_T17 is shown in bold, starting from position 1 and ending at position 207.

  The mutein T99080_PEA_4_P14 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript T99080_PEA_1_T18. The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein T99080_PEA_4_P14 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, enumerating other amino acids, and the last column shows SNPs as shown in Table 765) It indicates whether it is known and the presence of a known SNP in the mutant protein T99080_PEA_4_P14 sequence supports the predicted sequence of this mutant protein of the invention).

  The mutein T99080_PEA_4_P14 is encoded by the following transcript: T99080_PEA_4_T18 (sequences shown at the end of the application). The code portion of the transcript T99080_PEA_4_T18 is shown in bold, starting from position 226 and ending at position 480. The transcript also has the following SNPs listed in Table 766 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein T99080_PEA_4_P14 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein T99080_PEA_4_P15 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript T99080_PEA_1_T19. The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein T99080_PEA_4_P15 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows SNPs as shown in Table 767) It indicates whether it is known and the presence of a known SNP in the mutant protein T99080_PEA_4_P15 sequence supports the predicted sequence of this mutant protein according to the invention).

  The mutein T99080_PEA_4_P15 is encoded by the following transcript: T99080_PEA_4_T19 (sequences shown at the end of the application). The code portion of the transcript T99080_PEA_4_T19 is shown in bold, starting from position 226 and ending at position 459. The transcript also has the following SNPs listed in Table 768 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein T99080_PEA_4_P15 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein T99080_PEA_4_P16 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript T99080_PEA_1_T20. The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein T99080_PEA_4_P16 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, enumerating other amino acids, and the last column shows SNPs as shown in Table 769) It is shown whether it is known and the presence of a known SNP in the mutant protein T99080_PEA_4_P16 sequence supports the predicted sequence of this mutant protein of the invention).

  The mutein T99080_PEA_4_P16 is encoded by the following transcript: T99080_PEA_4_T20 (sequences shown at the end of the application). The code portion of the transcript T99080_PEA_4_T20 is shown in bold and this code portion starts from position 226 and ends at position 501. The transcript also has the following SNPs listed in Table 770 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein T99080_PEA_4_P16 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein T99080_PEA_4_P17 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript T99080_PEA_1_T21. The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein T99080_PEA_4_P17 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, enumerating other amino acids, and the last column shows the SNPs as shown in Table 771) It indicates whether it is known and the presence of a known SNP in the mutant protein T99080_PEA_4_P17 sequence supports the predicted sequence of this mutant protein of the invention).

  The mutein T99080_PEA_4_P17 is encoded by the following transcript: T99080_PEA_4_T21 (sequences shown at the end of the application). The code portion of transcript T99080_PEA_4_T21 is shown in bold, starting from position 226 and ending at position 426. The transcript also has the following SNPs listed in Table 772 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein T99080_PEA_4_P17 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  As mentioned above, cluster T99080 is characterized by the eleven segments listed in Table 2 above, the sequence of which is shown at the end of the application. These segments are part of the nucleic acid sequence, which are of particular interest and are individually described herein. A description of each segment of the invention is provided herein.

  The segment cluster T99080_PEA_4_node_1 of the present invention is supported by 5 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: T99080_PEA_4_T0, T99080_PEA_4_T6, T99080_PEA_4_T13, T99080_PEA_4_T18, T99080_PEA_4_T19, T99080_PEA_4_T20, and T99080_PEA_4. Table 773 below describes the start and end positions of this segment on each transcript.

  The segment cluster T99080_PEA_4_node_6 of the present invention is supported by three libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T99080_PEA_4_T17 and T99080_PEA_4_T21. Table 774 below describes the start and end positions of this segment on each transcript.

  The segment cluster T99080_PEA_4_node_11 of the present invention is supported by seven libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T99080_PEA_4_T14 and T99080_PEA_4_T20. Table 775 below describes the start and end positions of this segment on each transcript.

  The segment cluster T99080_PEA_4_node_19 of the present invention is supported by 59 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: T99080_PEA_4_T0, T99080_PEA_4_T2, and T99080_PEA_4_T4. Table 776 below describes the start and end positions of this segment on each transcript.

  The segment cluster T99080_PEA_4_node_20 of the present invention is supported by 98 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: T99080_PEA_4_T0, T99080_PEA_4_T2, T99080_PEA_4_T4, T99080_PEA_4_T6, T99080_PEA_4_T9, T99080_PEA_4_T10, T9080_PE4T4 14 0 14 PE Table 777 below describes the start and end positions of this segment on each transcript.

  According to an optional embodiment of the present invention, there is also provided a short segment associated with the above cluster. These segments are up to about 120 bp in length and are therefore included in the individual descriptions.

  The segment cluster T99080_PEA_4_node_3 of the present invention is supported by 40 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: T99080_PEA_4_T2, T99080_PEA_4_T9, T99080_PEA_4_T10, T99080_PEA_4_T11, T99080_PEA_4_T14, and T99080_PEA_4_T17. Table 778 below describes the start and end positions of this segment on each transcript.

  The segment cluster T99080_PEA_4_node_5 of the present invention is supported by 57 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: T99080_PEA_4_T0, T99080_PEA_4_T2, T99080_PEA_4_T6, T99080_PEA_4_T10, T99080_PEA_4_T14, T990_PE4_T14 005 004 004 005 004 005 024 Table 779 below describes the start and end positions of this segment on each transcript.

  The segment cluster T99080_PEA_4_node_8 of the present invention is supported by 12 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: T99080_PEA_4_T9, T99080_PEA_4_T10, T99080_PEA_4_T14, T99080_PEA_4_T18, and T99080_PEA_4_T20. Table 780 below describes the start and end positions of this segment on each transcript.

  Microarray (chip) data for this segment is also available, as follows. As described above, with respect to the clusters themselves, different oligonucleotides were tested for differential expression in different disease states, in particular cancer. The following oligonucleotides were found to reach this segment (for lung cancer) (shown in Table 781).

  The segment cluster T99080_PEA_4_node_13 of the present invention is supported by two libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T99080_PEA_4_T4. Table 782 below describes the start and end positions of this segment on each transcript.

  The segment cluster T99080_PEA_4_node_15 of the present invention is supported by six libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T99080_PEA_4_T11 and T99080_PEA_4_T19. Table 783 below describes the start and end positions of this segment on each transcript.

  The segment cluster T99080_PEA_4_node_18 of the present invention is supported by 5 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T99080_PEA_4_T0 and T99080_PEA_4_T2. Table 784 below describes the start and end positions of this segment on each transcript.

Mutated protein alignment against previously known proteins:

Sequence name: ACYO_HUMAN_V1



Sequence documentation:



Alignment of: T99080_PEA_4_P5 x ACYO_HUMAN_V1 ..



Alignment segment 1/1:



Quality: 973.00 Escore: 0

Matching length: 99 Total length: 99

Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00

Total Percent Similarity: 100.00 Total Percent Identity: 100.00

Gaps: 0



Alignment:

....

31 MAEGNTLISVDYEIFGKVQGVFFRKHTQAEGKKLGLVGWVQNTDRGTVQG 80

||||||||||||||||||||||||||||||||||||||||

1 MAEGNTLISVDYEIFGKVQGVFFRKHTQAEGKKLGLVGWVQNTDRGTVQG 50

....

81 QLQGPISKVRHMQEWLETRGSPKSHIDKANFNNEK VILKLDYSDFQIVK 129

||||||||||||||||||||||||||||||||||||||||

51 QLQGPISKVRHMQEWLETRGSPKSHIDKANFNNEK VILKLDYSDFQIVK 99













Sequence name: ACYO_HUMAN_V1



Sequence documentation:



Alignment of: T99080_PEA_4_P8 x ACYO_HUMAN_V1 ..



Alignment segment 1/1:



Quality: 711.00 Escore: 0

Matching length: 72 Total length: 72

Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00

Total Percent Similarity: 100.00 Total Percent Identity: 100.00

Gaps: 0



Alignment:

....

2 QAEGKKLGLVGWVQNTDRGTVQGQLQGPISKVRHMQEWLETRGSPKSHID 51

||||||||||||||||||||||||||||||||||||||||

28 QAEGKKLGLVGWVQNTDRGTVQGQLQGPISKVRHMQEWLETRGSPKSHID 77

.

52 KANFNNEKVILKLDYSDFQIVK 73

|||||||||||||||||||||

78 KANFNNEKVILKLDYSDFQIVK 99

Description of Cluster T08446 Cluster T08446 is characterized by two transcripts of interest and 36 segments, the names of which are shown in Tables 785 and 786, respectively, and the sequence itself is shown at the end of the application. Selected protein variants are shown in Table 787.

  These sequences are variants of Sorting nexin 26 (SwissProt accession identifier SNXQ_HUMAN) (SEQ ID NO: 1442), a known protein known previously as a protein previously known herein.

  Protein sorting nexin 26 is known or considered to have the following functions: It may be involved in several intracellular transport steps (due to similarity). The sequence of protein sorting nexin 26 is shown at the end of the application as "sorting nexin 26 amino acid sequence".

  The following GO annotation applies to previously known proteins. The following annotations were found: intracellular protein transport, which is an annotation related to biological processes, protein transporter, which is an annotation related to molecular function.

  GO assignments can be made at one or more http: // www. expasy. SwissProt / TremBl Protein knowledgebase available from ch / sprot / or http: // www. ncbi. nlm. nih. Depends on Locuslink available from gov / projects / LocusLink /.

  As mentioned above, cluster T08446 is characterized by the two transcripts listed in Table 1 above. These transcripts encode proteins that are variants of protein sorting nexin 26. A description of each mutein of the invention is provided herein.

  The mutein T08446_PEA_1_P18 according to the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript T08446_PEA_1_T2. An alignment to a known protein (sorting nexin 26) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report on comparison between T08446_PEA_1_P18 and SNXQ_HUMAN 1. Corresponding to amino acids 1-185 of SNXQ_HUMAN, first amino acid sequence at least 90% homologous to the corresponding MLSLSLCSHLWGPLILSALQARSTDSLDGPGEGSVQPLPTAGGPSVKGKPGKRLSAPRGPFPRLADCAHFHYENVDFGHIQLLLSPDREGPSLSGENELVFGVQVTCQGRSWPVLRSYDDFRSLDAHLHRCIFDRRFSCLPELPPPPEGARAAQMLVPLLLQYLETLSGLVDSNLNCGPVLTWME to amino acids 1-185 of T08446_PEA_1_P18, corresponding to amino acids 186-1305 of T08446_PEA_1_P18 sequence LDNHGRRLLLSEEASLNIPAVAAAHVIKRYTA APDELSFEVGDIVSVIDMPPTEDRSWWRGKRGFQVGFFPSECVELFTERPGPGLKADADGPPCGIPAPQGISSLTSAVPRPRGKLAGLLRTFMRSRPSRQRLRQRGILRQRVFGCDLGEHLSNSGQDVPQVLRCCSEFIEAHGVVDGIYRLSGVSSNIQRLRHEFDSERIPELSGPAFLQDIHSVSSLCKLYFRELPNPLLTYQLYGKFSEAMSVPGEEERLVRVHDVIQQLPPPHYRTLEYLLRHLARMARHSANTSMHARNLAIVWAPNLLRSMELESVGMGGAAAFREVRVQSVVVEFLLTHVDVLFSDTFTSAGLDPAGRCLLPRPKS AGSCPSTRLLTLEEAQARTQGRLGTPTEPTTPKAPASPAERRKGERGEKQRKPGGSSWKTFFALGRGPSVPRKKPLPWLGGTRAPPQPSGSRPDTVTLRSAKSEESLSSQASGAGLQRLHRLRRPHSSSDAFPVGPAPAGSCESLSSSSSSESSSSESSSSSSESSAAGLGALSGSPSHRTSAWLDDGDELDFSPPRCLEGLRGLDFDPLTFRCSSPTPGDPAPPASPAPPAPASAFPPRVTPQAISPRGPTSPASPAALDISEPLAVSVPPAVLELLGAGGAPASATPTPALSPGRSLRPHLIPLLLRGAEAPLTDACQQEMCSKLRGAQGP LGPDMESPLPPPPLSLLRPGGAPPPPPKNPARLMALALAERAQQVAEQQSQQECGGTPPASQSPFHRSLSLEVGGEPLGTSGSGPPPNSLAHPGAWVPGPPPYLPRQQSDGSLLRSQRPMGTSRRGLRGPAQVSAQLRAGGGGRDAPEAAAQSPCSVPSQVPTPGFFSPAPRECLPPFLGVPKPGLYPLGPPSFQPSSPAPVWRSSLGPPAPLDRGENLYYEIGASEGSPYSGPTRSWSPFRSMPPDRLNASYGMLGQSPPLHRSPDFLLSYPPAPSCFPPDHLGYSAPQHPARRPTPPEPLYVNLALGPRGPSPASSSSSSPPAHPRSRSDP A polypeptide having at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, more preferably at least 95%, and a second amino acid sequence homologous to the polypeptide comprising An isolated chimeric polypeptide encoding T08446_PEA_1_P18, wherein the one amino acid sequence and the second amino acid sequence are adjacent and in sequential order.

  2. Sequence in the T08446_PEA_1_P18 LDNHGRRLLLSEEASLNIPAVAAAHVIKRYTAQAPDELSFEVGDIVSVIDMPPTEDRSWWRGKRGFQVGFFPSECVELFTERPGPGLKADADGPPCGIPAPQGISSLTSAVPRPRGKLAGLLRTFMRSRPSRQRLRQRGILRQRVFGCDLGEHLSNSGQDVPQVLRCCSEFIEAHGVVDGIYRLSGVSSNIQRLRHEFDSERIPELSGPAFLQDIHSVSSLCKLYFRELPNPLLTYQLYGKFSEAMSVPGEEERLVRVHDVIQQLPPPHYRTLEYLLRHLARMARHSANTSMHARNLAIVWAPNLLRSMELES GMGGAAAFREVRVQSVVVEFLLTHVDVLFSDTFTSAGLDPAGRCLLPRPKSLAGSCPSTRLLTLEEAQARTQGRLGTPTEPTTPKAPASPAERRKGERGEKQRKPGGSSWKTFFALGRGPSVPRKKPLPWLGGTRAPPQPSGSRPDTVTLRSAKSEESLSSQASGAGLQRLHRLRRPHSSSDAFPVGPAPAGSCESLSSSSSSESSSSESSSSSSESSAAGLGALSGSPSHRTSAWLDDGDELDFSPPRCLEGLRGLDFDPLTFRCSSPTPGDPAPPASPAPPAPASAFPPRVTPQAISPRGPTSPASPAALDISEPLAVSVPPAVLELLGA GAPASATPTPALSPGRSLRPHLIPLLLRGAEAPLTDACQQEMCSKLRGAQGPLGPDMESPLPPPPLSLLRPGGAPPPPPKNPARLMALALAERAQQVAEQQSQQECGGTPPASQSPFHRSLSLEVGGEPLGTSGSGPPPNSLAHPGAWVPGPPPYLPRQQSDGSLLRSQRPMGTSRRGLRGPAQVSAQLRAGGGGRDAPEAAAQSPCSVPSQVPTPGFFSPAPRECLPPFLGVPKPGLYPLGPPSFQPSSPAPVWRSSLGPPAPLDRGENLYYEIGASEGSPYSGPTRSWSPFRSMPPDRLNASYGMLGQSPPLHRSPDFLLSYPPAPSCFPP DHLGYSAPQHPARRPTPPEPLYVNLALGPGPPSPASSSSSPPAHPRSRSDPGPP VPRLPQKQRAP WGPRTPHRVPGPWGPPPEPLLLYRAAPPAYGRGGELHRGSLYRNGGQRGEGAGPPPPYPTPSWSLH SEGQTRSYC and optionally at least about 80%, preferably at least about 85%, for example, for example, for example, Isolated polypeptide.

Report of the comparison between T08446_PEA_1_P18 and Q9NT23 (SEQ ID NO: 1443) Corresponding to amino acids 1 to 443 of T08446_PEA_1_P18 array MLSLSLCSHLWGPLILSALQARSTDSLDGPGEGSVQPLPTAGGPSVKGKPGKRLSAPRGPFPRLADCAHFHYENVDFGHIQLLLSPDREGPSLSGENELVFGVQVTCQGRSWPVLRSYDDFRSLDAHLHRCIFDRRFSCLPELPPPPEGARAAQMLVPLLLQYLETLSGLVDSNLNCGPVLTWMELDNHGRRLLLSEEASLNIPAVAAAHVIKRYTAQAPDELSFEVGDIVSVIDMPPTEDRSWWRGKRGFQVGFFPSECVELFTERPGPGLKADADGPPCGIPAPQGISSLTSAVPRPR KLAGLLRTFMRSRPSRQRLRQRGIRLQRVGFGCDLGEHLSNSGQDVPRCCSEFIEAHEVVDGIYRLSGVSSNIQLRHREFEDSERIPELSIPAPHQDIHSVSLCKLYFREPNLPLLTYQLYGKFSEAMSVPGEEERLVRV and at least 80%, at least 80%, and at least for the corresponding HDVI Q QLPPP PHYRTLEYLLRHLARMARHSANT SM HARNLA corresponding to ~ 674 and corresponding to amino acids 444 to 1117 of T08446_PEA_1_P18 VWAPNLLRSMELESVGMGGAAAFREVRVQSVVVEFLLTHVDVLFSDTFTSAGLDPAGRCLLPRPKSLAGSCPSTRLLTLEEAQARTQGRLGTPTEPTTPKAPASPAERRKGERGEKQRKPGGSSWKTFFALGRGPSVPRKKPLPWLGGTRAPPQPSGSRPDTVTLRSAKSEESLSSQASGAGLQRLHRLRRPHSSSDAFPVGPAPAGSCESLSSSSSSESSSSESSSSSSESSAAGLGALSGSPSHRTSAWLDDGDELDFSPPRCLEGLRGLDFDPLTFRCSSPTPGDPAPPASPAPPAPASAFPPRVTPQAISPRGPTSPASPAALDISEPL And at least 90% homologous second amino acid sequence AVSVPPAVLELLGAGGAPASATPTPALSPGRSLRPHLIPLLLRGAEAPLTDACQQEMCSKLRGAQGPLGPDMESPLPPPPLSLLRPGGAPPPPPKNPARLMALALAERAQQVAEQQSQQECGGTPPASQSPFHRSLSLEVGGEPLGTSGSGPPPNSLAHPGAWVPGPPPYLPRQQSDGSLLRSQRPMGTSRRGLRGPAQVSAQLRAGGGGRDAPEAAAQSPCSVPSQVPTPGFFSPAPRECLPPFLGVPKPGLYPLGPPSFQPSSPAPVWRSSLGPPAPLDRGENLYYEIGASEGSPYSG, T08446_PEA Crosslinking amino acid P corresponding to amino acid 1118 of 1_P18, corresponding to amino acids 676-862 of Q9NT23, and a corresponding TRSWSPFRSMPPDRLNASYGMLGQSPPLHRSPDFLLSYPPAPSCFPPDHLGYSAPQHPARRPTPPEPLYVNLALGPRGPSPASSSSSSPPAHPRSRSDPGPPVPRLPQKQRAPWGPRTPHRVPGPWGPPEPLLLYRAAPPAYGRGGELHRGSLYRNGGQRGEGAGPPPPYPTPSWSLHSEGQTRSYC at least 90% homologous third amino acid sequence to amino acids 1119-1305 of T08446_PEA_1_P18, the First amino acid sequence, second amino acid sequence, bridging amino acid, and 3 amino acid sequence, contiguous and in sequential order, the isolated chimeric polypeptide coding T08446_PEA_1_P18.

  2. Array of T08446_PEA_1_P18 MLSLSLCSHLWGPLILSALQARSTDSLDGPGEGSVQPLPTAGGPSVKGKPGKRLSAPRGPFPRLADCAHFHYENVDFGHIQLLLSPDREGPSLSGENELVFGVQVTCQGRSWPVLRSYDDFRSLDAHLHRCIFDRRFSCLPELPPPPEGARAAQMLVPLLLQYLETLSGLVDSNLNCGPVLTWMELDNHGRRLLLSEEASLNIPAVAAAHVIKRYTAQAPDELSFEVGDIVSVIDMPPTEDRSWWRGKRGFQVGFFPSECVELFTERPGPGLKADADGPPCGIPAPQGISSLTSAVPRPRGKLAGLLRTFMRSR At least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%. Isolated polypeptide.

Report of the comparison between T08446_PEA_1_P18 and Q96CP3 (SEQ ID NO: 1444) Corresponding to amino acids 1 to 1010 of T08446_PEA_1_P18 array MLSLSLCSHLWGPLILSALQARSTDSLDGPGEGSVQPLPTAGGPSVKGKPGKRLSAPRGPFPRLADCAHFHYENVDFGHIQLLLSPDREGPSLSGENELVFGVQVTCQGRSWPVLRSYDDFRSLDAHLHRCIFDRRFSCLPELPPPPEGARAAQMLVPLLLQYLETLSGLVDSNLNCGPVLTWMELDNHGRRLLLSEEASLNIPAVAAAHVIKRYTAQAPDELSFEVGDIVSVIDMPPTEDRSWWRGKRGFQVGFFPSECVELFTERPGPGLKADADGPPCGIPAPQGISSLTSAVPRP GKLAGLLRTFMRSRPSRQRLRQRGILRQRVFGCDLGEHLSNSGQDVPQVLRCCSEFIEAHGVVDGIYRLSGVSSNIQRLRHEFDSERIPELSGPAFLQDIHSVSSLCKLYFRELPNPLLTYQLYGKFSEAMSVPGEEERLVRVHDVIQQLPPPHYRTLEYLLRHLARMARHSANTSMHARNLAIVWAPNLLRSMELESVGMGGAAAFREVRVQSVVVEFLLTHVDVLFSDTFTSAGLDPAGRCLLPRPKSLAGSCPSTRLLTLEEAQARTQGRLGTPTEPTTPKAPASPAERRKGERGEKQRKPGGSSWKTFFALGRGPSVPRKKPLPWLGG RAPPQPSGSRPDTVTLRSAKSEESLSSQASGAGLQRLHRLRRPHSSSDAFPVGPAPAGSCESLSSSSSSESSSSESSSSSSESSAAGLGALSGSPSHRTSAWLDDGDELDFSPPRCLEGLRGLDFDPLTFRCSSPTPGDPAPPASPAPPAPASAFPPRVTPQAISPRGPTSPASPAALDISEPLAVSVPPAVLELLGAGGAPASATPTPALSPGRSLRPHLIPLLLRGAEAPLTDACQQEMCSKLRGAQGPLGPDMESPLPPPPLSLLRPGGAPPPPPKNPARLMALALAERAQQVAEQQSQQECGGTPPASQSPFHRSLSLEVGGEPLGTSG The first amino acid sequence which is at least 70%, optionally at least 80%, preferably at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous to the polypeptide having SGPP LRGPAQVSAGGRAGGADGAPEAAAQSPCSVP SQVPTPGFSPLAPGPFPGPGPGPGLYPGSFSPSSPAPVWRSSLGPPALDRYGENLYYEIGASEGSPPYSGPTRSWSPRFSPMPPDRPNASLSPMPGL PDFLLSYPPAPSCFPPDHLGYSAPQHPARRPTPPEPLYVNLALGPRGPSPASSSSSSPPAHPRSRSDPGPPVPRLPQKQRAPWGPRTPHRVPGPWGPPEPLLLYRAAPPAYGRGGELHRGSLYRNGGQRGEGAGPPPPYPTPSWSLHSEGQTRSYC and and at least 90% homologous to a second amino acid sequence, the first amino acid sequence and a second amino acid sequence, contiguous and in sequential order, the isolated chimeric polypeptide coding T08446_PEA_1_P18.

  2. Array of T08446_PEA_1_P18 MLSLSLCSHLWGPLILSALQARSTDSLDGPGEGSVQPLPTAGGPSVKGKPGKRLSAPRGPFPRLADCAHFHYENVDFGHIQLLLSPDREGPSLSGENELVFGVQVTCQGRSWPVLRSYDDFRSLDAHLHRCIFDRRFSCLPELPPPPEGARAAQMLVPLLLQYLETLSGLVDSNLNCGPVLTWMELDNHGRRLLLSEEASLNIPAVAAAHVIKRYTAQAPDELSFEVGDIVSVIDMPPTEDRSWWRGKRGFQVGFFPSECVELFTERPGPGLKADADGPPCGIPAPQGISSLTSAVPRPRGKLAGLLRTFMRSR SRQRLRQRGILRQRVFGCDLGEHLSNSGQDVPQVLRCCSEFIEAHGVVDGIYRLSGVSSNIQRLRHEFDSERIPELSGPAFLQDIHSVSSLCKLYFRELPNPLLTYQLYGKFSEAMSVPGEEERLVRVHDVIQQLPPPHYRTLEYLLRHLARMARHSANTSMHARNLAIVWAPNLLRSMELESVGMGGAAAFREVRVQSVVVEFLLTHVDVLFSDTFTSAGLDPAGRCLLPRPKSLAGSCPSTRLLTLEEAQARTQGRLGTPTEPTTPKAPASPAERRKGERGEKQRKPGGSSWKTFFALGRGPSVPRKKPLPWLGGTRAPPQPSGSRPDTV LRSAKSEESLSSQASGAGLQRLHRLRRPHSSSDAFPVGPAPAGSCESLSSSSSSESSSSESSSSSSESSAAGLGALSGSPSHRTSAWLDDGDELDFSPPRCLEGLRGLDFDPLTFRCSSPTPGDPAPPASPAPPAPASAFPPRVTPQAISPRGPTSPASPAALDISEPLAVSVPPAVLELLGAGGAPASATPTPALSPGRSLRPHLIPLLLRGAEAPLTDACQQEMCSKLRGAQGPLGPDMESPLPPPPLSLLRPGGAPPPPPKNPARLMALALAERAQQVAEQQSQQECGGTPPASQSPFHRSLSLEVGGEPLGTSGSGPPPNSLAHPGAWV Encodes the tip of T08446_PEA_1_P18, which contains a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to PGPPPPLPMQQSDGSLRLRSPRPMGTSRRG Isolated polypeptide.

Report of the comparison between T08446_PEA_1_P18 and BAC86902 (SEQ ID NO: 1445) A sequence corresponding to amino acids 1 to 154 of T08446_PEA_1_P18 is a table that includes a pair of at least a pair of at least 15: Amino acid sequence corresponding to amino acids 1-861 of BAC86902 and amino acids 155-1015 of T08446_PEA_1_P18. MLVPLLLQYLETLSGLVDSNLNCGPVLTWMELDNHGRRLLLSEEASLNIPAVAAAHVIKRYTAQAPDELSFEVGDIVSVIDMPPTEDRSWWRGKRGFQVGFFPSECVELFTERPGPGLKADADGPPCGIPAPQGISSLTSAVPRPRGKLAGLLRTFMRSRPSRQRLRQRGILRQRVFGCDLGEHLSNSGQDVPQVLRCCSEFIEAHGVVDGIYRLSGVSSNIQRLRHEFDSERIPELSGPAFLQDIHSVSSLCKLYFRELPNPLLTYQLYGKFSEAMSVPGEEERLVRVHDVIQQLPPPHYRTLEYLLRHLARMARHSANTSMHARN also corresponding AIVWAPNLLRSMELESVGMGGAAAFREVRVQSVVVEFLLTHVDVLFSDTFTSAGLDPAGRCLLPRPKSLAGSCPSTRLLTLEEAQARTQGRLGTPTEPTTPKAPASPAERRKGERGEKQRKPGGSSWKTFFALGRGPSVPRKKPLPWLGGTRAPPQPSGSRPDTVTLRSAKSEESLSSQASGAGLQRLHRLRRPHSSSDAFPVGPAPAGSCESLSSSSSSESSSSESSSSSSESSAAGLGALSGSPSHRTSAWLDDGDELDFSPPRCLEGLRGLDFDPLTFRCSSPTPGDPAPPASPAPPAPASAFPPRVTPQAISPRGPTSPASPAALDISE And at least 90% homologous second amino acid sequence PierueibuiesubuiPiPieibuieruieruerujieijijieiPieiesueitiPitiPieieruesuPijiaruesueruaruPieichieruaiPieruerueruarujieiieiPierutidieishikyukyuiemushiesukeieruarujieikyuJipieruJipidiemuiesupierupipipipieruesuerueruaruPijijieiPipipipipikeienuPieiarueruemueierueierueiiarueikyukyubuieiikyukyuesukyukyuishijijitiPiPieiesukyuesuPiefueichiaruesueruesueruibuijijiiPierujitiesujiesuJipipipienuesuerueieichiPijieidaburyubuiPiJipipipiwaieruPiaruQQSDGSLLRSQRPMGTSRRGLRGPA, polypeptide at least 70% with a sequence corresponding to QVSAQLRAGGGGRDAPEAAAQSPCSVPS amino acid 1016-1043 of T08446_PEA_1_P18, optionally at least 80%, preferably at least GIV GIVIGITIGH A fourth amino acid sequence homologous to the sequence APQHPARRPTPPEPLYVNLALGPRGPSPASSSSSS corresponding to amino acids 1172 to 1305 of T08446_PEA_1_P18 A polypeptide having at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous to a polypeptide having at least 70%, preferably at least 85%, more preferably at least 90%; An isolated chimeric polypeptide encoding T08446_PEA_1_P18, wherein the amino acid sequence of 1, the second amino acid sequence, the third amino acid sequence, the fourth amino acid sequence, and the fifth amino acid sequence are adjacent and in sequential order .

  2. A sequence of T08446_PEA_1_P18 of the T08446_PEA_1_P18 (same as in the lower part in the lower part of the U14Gullus).... An isolated polypeptide encoding

  3. T08446_PEA_1_P18 corresponding amino acid sequence that is at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence encoding QVSAQLRAGGGGRDAPEAAAQSPCSVPS An isolated polypeptide encoding the edge portion of T08446_PEA_1_P18, which comprises

  4. In the T08446_PEA_1_P18, in the T08446_PEA1_P18 in the T08446_PEA. An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein T08446_PEA_1_P18 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows SNPs as shown in Table 788) It indicates whether it is known and the presence of a known SNP in the mutein T08446_PEA_1_P18 sequence supports the putative sequence of this mutein of the invention).

  The mutein T08446_PEA_1_P18 is encoded by the following transcript: T08446_PEA_1_T2 (sequences shown at the end of the application). The coding portion of transcript T08446_PEA_1_T2 is shown in bold, starting at position 228 and ending at position 4142. The transcript also has the following SNPs listed in Table 789 (indicating its position on the nucleotide sequence and listing another nucleic acid, the last column indicating whether the SNP is known, mutein T08446_PEA_1_P18 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein T08446_PEA_1_P19 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript T08446_PEA_1_T22. The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein T08446_PEA_1_P19 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows SNPs as shown in Table 790) It is shown whether it is known and the presence of a known SNP in the mutein T08446_PEA_1_P19 sequence supports the putative sequence of this mutein of the invention).

  The mutein T08446_PEA_1_P19 is encoded by the following transcript: T08446_PEA_1_T22 (sequences shown at the end of the application). The code portion of transcript T08446_PEA_1_T22 is shown in bold and this code portion starts at position 228 and ends at position 965. The transcript also has the following SNPs listed in Table 791 (showing its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein T08446_PEA_1_P19 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  As mentioned above, cluster T08446 is characterized by the 36 segments listed in Table 2 above, the sequence of which is shown at the end of the application. These segments are part of the nucleic acid sequence, which are of particular interest and are individually described herein. A description of each segment of the invention is provided herein.

  The segment cluster T08446_PEA_1_node_2 of the present invention is supported by one library. The number of libraries was determined as described above. This segment can be found in the following transcript: T08446_PEA_1_T2 and T08446_PEA_1_T22. Table 792 below describes the start and end positions of this segment on each transcript.

  The segment cluster T08446_PEA_1_node_9 of the present invention is supported by 17 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T08446_PEA_1_T2 and T08446_PEA_1_T22. Table 793 below describes the start and end positions of this segment on each transcript.

  The segment cluster T08446_PEA_1_node_15 of the present invention is supported by 0 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T08446_PEA_1_T22. Table 794 below describes the start and end positions of this segment on each transcript.

  The segment cluster T08446_PEA_1_node_17 of the present invention is supported by 22 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T08446_PEA_1_T2. Table 794 below describes the start and end positions of this segment on each transcript.

  The segment cluster T08446_PEA_1_node_25 of the present invention is supported by 24 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T08446_PEA_1_T2. Table 12 below describes the start and end positions of this segment on each transcript.

  The segment cluster T08446_PEA_1_node_29 of the present invention is supported by 25 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T08446_PEA_1_T2. Table 795 below describes the start and end positions of this segment on each transcript.

  The segment cluster T08446_PEA_1_node_38 of the present invention is supported by 20 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T08446_PEA_1_T2. Table 796 below describes the start and end positions of this segment on each transcript.

  The segment cluster T08446_PEA_1_node_43 of the present invention is supported by 15 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T08446_PEA_1_T2. Table 797 below describes the start and end positions of this segment on each transcript.

  The segment cluster T08446_PEA_1_node_51 of the present invention is supported by 19 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T08446_PEA_1_T2. Table 798 below describes the start and end positions of this segment on each transcript.

  The segment cluster T08446_PEA_1_node_52 of the present invention is supported by 15 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T08446_PEA_1_T2. Table 799 below describes the start and end positions of this segment on each transcript.

  The segment cluster T08446_PEA_1_node_55 of the present invention is supported by 21 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T08446_PEA_1_T2. Table 800 below describes the start and end positions of this segment on each transcript.

  The segment cluster T08446_PEA_1_node_57 of the present invention is supported by 37 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T08446_PEA_1_T2. Table 801 below lists the start and end positions of this segment on each transcript.

  The segment cluster T08446_PEA_1_node_59 of the present invention is supported by 36 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T08446_PEA_1_T2. Table 802 below describes the start and end positions of this segment on each transcript.

  The segment cluster T08446_PEA_1_node_62 of the present invention is supported by 36 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T08446_PEA_1_T2. Table 803 below describes the start and end positions of this segment on each transcript.

  The segment cluster T08446_PEA_1_node_63 of the present invention is supported by 64 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T08446_PEA_1_T2. Table 804 below describes the start and end positions of this segment on each transcript.

  According to an optional embodiment of the present invention, there is also provided a short segment associated with the above cluster. These segments are up to about 120 bp in length and are therefore included in the individual descriptions.

  The segment cluster T08446_PEA_1_node_3 of the present invention is supported by 14 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T08446_PEA_1_T2 and T08446_PEA_1_T22. Table 805 below describes the start and end positions of this segment on each transcript.

  The segment cluster T08446_PEA_1_node_5 of the present invention is supported by 17 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T08446_PEA_1_T2 and T08446_PEA_1_T22. Table 806 below describes the start and end positions of this segment on each transcript.

  Microarray (chip) data for this segment is also available, as follows. As described above, with respect to the clusters themselves, different oligonucleotides were tested for differential expression in different disease states, in particular cancer. The following oligonucleotides were found to reach this segment (for lung cancer) (shown in Table 807).

  The segment cluster T08446_PEA_1_node_7 of the present invention is supported by 19 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T08446_PEA_1_T2 and T08446_PEA_1_T22. Table 808 below describes the start and end positions of this segment on each transcript.

  Microarray (chip) data for this segment is also available, as follows. As described above, with respect to the clusters themselves, different oligonucleotides were tested for differential expression in different disease states, in particular cancer. The following oligonucleotides were found to reach this segment (for lung cancer) (shown in Table 809).

  The segment cluster T08446_PEA_1_node_12 of the present invention is supported by 14 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T08446_PEA_1_T2 and T08446_PEA_1_T22. Table 810 below describes the start and end positions of this segment on each transcript.

  The segment cluster T08446_PEA_1_node_13 of the present invention is supported by 0 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T08446_PEA_1_T22. Table 811 below describes the start and end positions of this segment on each transcript.

  The segment cluster T08446_PEA_1_node_19 of the present invention is supported by 19 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T08446_PEA_1_T2. Table 812 below describes the start and end positions of this segment on each transcript.

  The segment cluster T08446_PEA_1_node_21 of the present invention is supported by 21 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T08446_PEA_1_T2. Table 813 below describes the start and end positions of this segment on each transcript.

  The segment cluster T08446_PEA_1_node_23 of the present invention is supported by 22 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T08446_PEA_1_T2. Table 814 below describes the start and end positions of this segment on each transcript.

  The segment cluster T08446_PEA_1_node_27 of the present invention is supported by 23 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T08446_PEA_1_T2. Table 815 below describes the start and end positions of this segment on each transcript.

  The segment cluster T08446_PEA_1_node_32 of the present invention is supported by 23 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T08446_PEA_1_T2. Table 816 below describes the start and end positions of this segment on each transcript.

  The segment cluster T08446_PEA_1_node_34 of the present invention is supported by 22 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T08446_PEA_1_T2. Table 817 below describes the start and end positions of this segment on each transcript.

  The segment cluster T08446_PEA_1_node_45 of the present invention is supported by 19 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T08446_PEA_1_T2. Table 818 below describes the start and end positions of this segment on each transcript.

  The segment cluster T08446_PEA_1_node_46 of the present invention is supported by 18 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T08446_PEA_1_T2. Table 819 below describes the start and end positions of this segment on each transcript.

  The segment cluster T08446_PEA_1_node_48 of the present invention is supported by 19 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T08446_PEA_1_T2. Table 820 below describes the start and end positions of this segment on each transcript.

  The segment cluster T08446_PEA_1_node_54 according to the invention can be found in the following transcript: T08446_PEA_1_T2. Table 821 below describes the start and end positions of this segment on each transcript.

  The segment cluster T08446_PEA_1_node_58 of the present invention is supported by 13 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T08446_PEA_1_T2. Table 822 below describes the start and end positions of this segment on each transcript.

  The segment cluster T08446_PEA_1_node_60 of the present invention is supported by 27 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T08446_PEA_1_T2. Table 823 below describes the start and end positions of this segment on each transcript.

  The segment cluster T08446_PEA_1_node_61 of the present invention is supported by 25 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T08446_PEA_1_T2. Table 824 below describes the start and end positions of this segment on each transcript.

  The segment cluster T08446_PEA_1_node_64 according to the invention can be found in the following transcript: T08446_PEA_1_T2. Table 825 below describes the start and end positions of this segment on each transcript.

  The segment cluster T08446_PEA_1_node_65 of the present invention is supported by 39 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T08446_PEA_1_T2. Table 826 below describes the start and end positions of this segment on each transcript.

  The segment cluster T08446_PEA_1_node_66 of the present invention is supported by 29 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T08446_PEA_1_T2. Table 827 below describes the start and end positions of this segment on each transcript.

Mutated protein alignment against previously known proteins:

Sequence name: SNXQ_HUMAN



Sequence documentation:



Alignment of: T08446_PEA_1_P18 x SNXQ_HUMAN ..



Alignment segment 1/1:



Quality: 1835.00 Escore: 0

Matching length: 185 Total length: 185

Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00

Total Percent Similarity: 100.00 Total Percent Identity: 100.00

Gaps: 0



Alignment:

....

1 MLSLSLCSHLWGPLILSALQARSTDSLDGPGEGSVQPLPGPGPSVKGP 50

||||||||||||||||||||||||||||||||||||||||

1 MLSLSLCSHLWGPLILSALQARSTDSLDGPGEGSVQPLPGPGPSVKGP 50

....

51 GKRLSAPRGP FPRLADCAHFHYENVDFGHIQLLSPDREGPSLSGENELV 100

||||||||||||||||||||||||||||||||||||||||

51 GKRLSAPRGP FPRLADCAHFHYENVDFGHIQLLSPDREGPSLSGENELV 100

....

101 FGVQ VTCQGRSWPVLRSYDDFRSLDAHLHRCIFDRRFSCLEPLPPPPEGA 150

||||||||||||||||||||||||||||||||||||||||

101 FGVQ VTCQGRSWPVLRSYDDFRSLDAHLHRCIFDRRFSCLEPLPPPPEGA 150

....

151 RAAQMLVPLLLQYLETLSGLVDSNLNCGPVLTWME 185

||||||||||||||||||||||||||||||||

151 RAAQMLVPLLLQYLETLSGLVDSNLNCGPVLTWME 185













Sequence name: Q9NT23



Sequence documentation:



Alignment of: T08446_PEA_1_P18 x Q9NT23 ..



Alignment segment 1/1:



Quality: 8548.00 Escore: 0

Matching length: 862 Total length: 862

Matching Percent Similarity: 99.88 Matching Percent Identity: 99.88

Total Percent Similarity: 99.88 Total Percent Identity: 99.88

Gaps: 0



Alignment:

....

444 HDVIQQLPPPHYRTLEYLLRHLARMARHSANTSMHARNLAIVWAPFNLLRS 493

||||||||||||||||||||||||||||||||||||||||

1 HDVIQQLPPPHYRTLEYLLRHLARMARHSANTSMHARNLAIVWAPFNLLRS 50

....

494 MELESVGMGGAAAFREVRVQSVVVEFLLTHVDVLFSDTFTSAGLDPAGRC 543

||||||||||||||||||||||||||||||||||||||||

51 MELESVGMGGAAAFREVRVQSVVVEFLLTHVDVLFSDTFTSAGLDPAGRC 100

....

544 LLPRPKSLAGSCPSTRLLTLEEAQARTQGRL GTPTEPTTPKAPASPAERR 593

||||||||||||||||||||||||||||||||||||||||

101 LLPRPKSLAGSCPSTRLL TLEEAQARTQGRL GTPTEPTTPKAPAS PAERR 150

....

594 KERGGEKQRKPGGSSWKTFFALGRGPSVPRKKPLPWLGGTRAPPGPPSGSR 643

||||||||||||||||||||||||||||||||||||||||

151 KERGGEKQRKPGGSSWKTFFALGRGPSVPRKKPLPWLGGTRAPPAPPPSGSR 200

....

644 PDTVTLRSAKSEESLSSQASGAGLQRLHRLRRPHSSSDAFPVGPAPAGSC 693

||||||||||||||||||||||||||||||||||||||||

201 PDTVTLRSAKSEESLSSQASGAGLQRLHRLRRPHSSSDAFPVGPAPAGSC 250

....

694 ESL SS SS SS ESS SS ESS SS SS AAGALGAL SG SP SHRT SAW LD D G D DD 743

||||||||||||||||||||||||||||||||||||||||

251 ESL SS SS SS ESS SS ESS SS SS AAGALGAL SG SP SHRT SAW LD D G D DD 300

....

744 FSPP RCLEGLRGLDFTLTCSSPSTPGDPAPPAPPAPASPFPPRVT 793

||||||||||||||||||||||||||||||||||||||||

301 FSPP RCLEGLRGLDFTLTCSSPSTPGDPAPPAPPAPASPFPPRVT 350

....

794 PQAISPRGPTSPAPALDISEPLAVSVPPAVLELLGAGGASATPTPA 843

||||||||||||||||||||||||||||||||||||||||

351 PQAISPRGPTSPAPALDISEPLAVSVPPAVLELLGAGGASATPTPA 400

....

844 LSPGRSLPHLIPLLLRGA EAPLTDACQQEMCS KLRGAQGPLGPDMESPL 893

||||||||||||||||||||||||||||||||||||||||

401 LSPGRSLRPHLIPLLLRGA EAPLTDACQQEMCS KLRGAQGPLGPDMESPL 450

....

894 PPPPLSLLPG GAPPPPPKNPARLMALALAERAQQVAEQQSQQECGTRPP 943

||||||||||||||||||||||||||||||||||||||||

451 PPPPLSLLPGGAPPPPPKNPARLMALALAERAQQVAEQQSQQECGTGPTP 500

....

944 ASQSPFHRSLSLEVGGEPLGTSGSGPPPNSLAHPGAWVPGPPPYLPRQQS 993

||||||||||||||||||||||||||||||||||||||||

501 ASQSPFHRSLSLEVGGEPLGTSGSGPPPNSLAHPGAWVPGPPPYLPRQQS 550

....

994 DGSL LRSQ RPM GTS RRGL RG PAQ VS AQL RAGGGGRD APEAAAQSPCS VPS 1043

||||||||||||||||||||||||||||||||||||||||

551 DGSLLRSQRPMGTTSRGLRGPAQVSAQLRAGGGGRDAPEAAAQSPCSVPS 600

....

1044 QVPTPGFFSPA PRECLEPPFLGVPKPGLYPLGPPSFQPSSPAVWRSSLGP 1093

||||||||||||||||||||||||||||||||||||||||

601 QVPTPGFFSPA PRECLEPPFLGVPKPGLYPLGPPSFQPSSPAVWRSSLGP 650

....

1094 PAPLDRGENLYYEIGASEGSPYSGPTRSWSPFRSPPDRLNASYGMLGQS 1143

||||||||||||||||||||||||||||||||||||||||

651 PAPLDRGENLYYEIGASEGSPYSGLTRSWSPFRPSMPPDRLNASYGMLGQS 700

....

1144 PPLHRSPDFLLSYPPAPSCFPPDHLGYSAPQHPARRPTPPEPLYVNLALG 1193

||||||||||||||||||||||||||||||||||||||||

701 PPLHRSPDFLLSYPPAPSCFPPDHLGYSAPQHPARRPTPPEPLYVNLALG 750

....

1194 PRGPS PASS SS SPSP HPRS RSDP GPP VPRLP Q KQ RAPG GPR PHR VPGP 1243

||||||||||||||||||||||||||||||||||||||||

751 PRGPS PASS SS SSPP HPR RSDP GPP VPRLPQ KQ RAP W GPRT PHRVP GP 800

....

1244 WGPPEPLLLYRAAPPAYGRGGELHRGSLYRNGGQRGEGAGPPPPYPTPSW 1293

||||||||||||||||||||||||||||||||||||||||

801 WGPPEPLLLYRAAPPAYGRGGELHRGSLYRNGGQRGEGAGPPPPYPTPSW 850

.

1294 SLHSEGQTRSYC 1305

||||||||||||

851 SLHSEGQTRSYC 862













Sequence name: Q96CP3



Sequence documentation:



Alignment of: T08446_PEA_1_P18 x Q96CP3 ..



Alignment segment 1/1:



Quality: 3019.00 Escore: 0

Matching length: 295 Total length: 295

Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00

Total Percent Similarity: 100.00 Total Percent Identity: 100.00

Gaps: 0



Alignment:

....

1011 LRGPAQ VSAQLRAGGGGRDAPEAAAQSPCSVPSQ VPTPGFSPAPRECLP 1060

||||||||||||||||||||||||||||||||||||||||

1 LRGPAQVSAQLRAGGGGRDAPEAAAQSPCSVSPQ VPTPGFSPAPRECLP 50

....

1061 PFLGVPKPGLYPLGPPSFQPSSPAVVWRSSLGPP APLDRGENLYYEIGAS 1110

||||||||||||||||||||||||||||||||||||||||

51 PFLGVPKPGLYPLGPPSFQPSSPAVVWRSSLGPP APLDRGENLYYEIGAS 100

....

1111 EGSPYSGPTRSWSPFRSPMPPDRLNASYGMLGQSPLHRSPDFLLSYPPAP 1160

||||||||||||||||||||||||||||||||||||||||

101 EGSPYSGPTRSWSPFRSPDPRLNASYGMLGQSPPLHRSPDFLLSYPPAP 150

....

1161 SCFPPDHLGYSAPQHPARRPTPPEPLYVNLALGPRPPSPASSSSSSPPAH 1210

||||||||||||||||||||||||||||||||||||||||

151 SCFPPDHLGYSAPQHPARRPTPPEPLYVNLALGPRPPSPASSSSSSPPAH 200

....

1211 PRSR SDP GPP VPRLP QKQ RAP WGPRT PHRVPGPWGPPEPPLLLYRAAPPAY 1260

||||||||||||||||||||||||||||||||||||||||

201 PRSR SDP GPP V PRLP Q KQ RAP W PRTP R PR VPG P W GPP PLLLRA APPAY 250

....

1261 GRGGELHRGSLYRNGGQRGEGAGPPPPYPTPTSWLSEGQTRSYC 1305

|||||||||||||||||||||||||||||||||||||||

251 GRGGELHRGSLYRNGGQRGEGAGPPPPYPTPTSWLSEGQTRSYC 295













Sequence name: BAC86902



Sequence documentation:



Alignment of: T08446_PEA_1_P18 x BAC86902 ..



Alignment segment 1/1:



Quality: 9651.00 Escore: 0

Matching length: 991 Total length: 1019

Matching Percent Similarity: 99.90 Matching Percent Identity: 99.90

Total Percent Similarity: 97.15 Total Percent Identity: 97.15

Gaps: 1



Alignment:

....

155 MLVPLLLQYLETLSGLVDNNL NCGPVLTWMELDNHGRRLLLSEALSNIP 204

||||||||||||||||||||||||||||||||||||||||

1 MLVPLLLQYLETLSGLVDSNLNCGPVLTWMELDNHGRRLLLSEEASLNIP 50

....

205 AVAAAHVIKRYTAQAPLELSFEVGDIVSVIDMPPTEDRSWRGRGQQVG 254

||||||||||||||||||||||||||||||||||||||||

51 AVAAAHVIKRYTAQAPLELSFEVGDIVSVIDMPPTEDRSWRGKRGFQ 100

....

255 FFPSECVELFTERPGPGLKADADGPPCGIPAPQGISSLTSAVPRPRGKLA 304

||||||||||||||||||||||||||||||||||||||||

101 FFPSECVELFTERPGPGLKADADGPPCGIPAPQ GISSLTSAVPRPRGKLA 150

....

305 GLLRTFMRSRPRQLRRQRGILRQRFGFGCDLGEHLSNSGQDVPQVLRCCS 354

||||||||||||||||||||||||||||||||||||||||

151 GLLRTFMRSRPSRQRLRQRGILRQRFGFGCDLGEHLSNSGQDVPQVLRCCS 200

....

355 EFIEAHGVVDGIYRLSGVSSNIQLRLREFFDERIPELSGPAFLQDIHSVS 404

||||||||||||||||||||||||||||||||||||||||

201 EFIEAHGVVDGIYRLSGVSSNIQRLRHEFDSERIPELSGPAFLQDIHSVS 250

....

405 SLCKLYFREPNNPLLTYQLYGKFSEAMSVPGEEERLVRVHDVIQQLPPP 454

||||||||||||||||||||||||||||||||||||||||

251 SLCKLYFREPNNPLLTYQLYGKFSEAMSVPGEEERLVRVHDVIQQLPPP 300

....

455 YRTLEYLLRHLARMARHSANTSMHARNLAIVWAPNLLRMSMELESVGMGA 504

||||||||||||||||||||||||||||||||||||||||

301 YRTLEYLLRHLARMARHSANTSMHARNLAIVWAPNLLRMSMELESVGMGGA 350

....

505 AAFREVRVQSVVVEFLLTHVDVLFSDTFTSAGLDPAGRCLLPRPKSLAGS 554

||||||||||||||||||||||||||||||||||||||||

351 AAFREVRVQSVVVEFLLTHVDVLFSDTFTSAGLDPAGRCLLPRPKSLAGS 400

....

555 CPSTRLLTLEEAQARTQGRL GTPTEPTTPKAPASPAERRKGERGEKQRKP 604

||||||||||||||||||||||||||||||||||||||||

401 CPSTRLLTLEEAQARTQGRL GTPTEPTTPKAPASPAERRKGERGEKQRKP 450

....

605 GGSSWKTFFALGRGPSVPRKKPLPWLGGTRAPPQPSGSRPDTVTLSAKS 654

||||||||||||||||||||||||||||||||||||||||

451 GGSSWKTFFALGRGPSVPRKKPLPWLGGTRAPPGPPSGSRPDTVTLSAKS 500

....

655 EESLSSQASGAGLQRLHRLRRPHSSDSAFPVGPAPAGSCESLSSSSSES 704

||||||||||||||||||||||||||||||||||||||||

501 EESLSSQASGAGLQRLHRLRRPHSSSDAFPVGPAPAGSCESLSSSSSES 550

....

705 SSSESSSSSSESSAAGLGALSGSPSHRTSALDLDDHDPRPPRCLEGLR 754

||||||||||||||||||||||||||||||||||||||||

551 SSSSESSSSSSESSAAGLGALSGSPSHRTSALDLDDELDFPPCREGLR 600

....

755 GLDFDPLTFRCSSTPDPDPAPPASPAPPAPASAFPPRVTPQAISPRGPTS 804

||||||||||||||||||||||||||||||||||||||||

601 GLDFDPLTFRCSSTPDPDPAPPASPAPPAPASAFPPRVTPQAISPRGPTS 650

....

805 PASPAALDISEPLAVPSVPPAVLELLGAGGAPASATPTPALSPGRSLRPHL 854

||||||||||||||||||||||||||||||||||||||||

651 PASPAALDISEPLAVPSVPPAVLELLGAGGAPASATPTPALSPGRSLRPHL 700

....

855 IPLLLRGAEAPLTDACQQEMCS KLRGAQGPLGPDMESPLPPPSLLRPG 904

||||||||||||||||||||||||||||||||||||||||

701 IPLLLRGAEAPLTDACQQEMCS KLRGAQGPLGPDMESPLPPPLSLLPG 750

....

905 GAPPPPPKNPARLMALALAERAQQVAEQQSQQEGGPTPASQSPFHRSLS 954

||||||||||||||||||||||||||||||||||||||||

751 GAPPPPPKNPARLMALALAERAQQVAEQQSQQEGGPTPASQSPFHRSLS 800

....

955 LEVGGEPLGT SGSGPPPNSLAHPGAWVPGPPPYLPRQQSDGSLLRSPRPM 1004

||||||||||||||||||||||||||||||||||||||||

801 LEVGGEPLGTGSGSGPPPNSLAHPGAWVPGPPPYLPRQQSDGSLLRSPRPM 850

....

1005 GTSRRGLRGPAQVSAQLRAGGGGRDAPEAAAQSPCSVSPQVPTPGFSPA 1054

|||||||||||||||||||||

851 GTSRRGLRGPA ........................ QVPTPGFFSPA 872

....

1055 PRECLPPFLGVPKPGLYPLGPPSFQPSSPAVVWRSSLGPPAPLDRGENLY 1104

||||||||||||||||||||||||||||||||||||||||

873 PRECLPFLFVPKPGLYPLGPPSFQPSSPAVVWRSSLGPPAPLDRGENLY 922

....

1105 YEIGASEGSPPYSGPTRSWSPFRSMPPDRLNASYGMLGQSPLHRSPDFLL 1154

||||||||||||||||||||||||||||||||||||||||

923 YEIGASEGSPPYS GPPTRSSWSPRSMPPDRLNASYGMLGQSPPLHRSPDFLL 972

.

1155 SYPPAP SCFPPDHLGYSAP 1173

||||||||||||||||

973 SYPPAP SCFPPDHLGYSPP 991

Description of cluster HUMCA1XIA The cluster HUMCA1XIA is characterized by 4 transcripts and 46 segments of interest, the names of which are shown in Tables 828 and 829, respectively, and the sequence itself is shown at the end of the application. Selected protein variants are shown in Table 830.

  These sequences are variants of collagen alpha 1 (SwissProt accession identifier CA1B_HUMAN) (SEQ ID NO: 1446), which is a known protein known previously as a protein previously known herein.

  The protein collagen alpha 1 is known or considered to have the following functions: It may play an important role in fibrillogenesis by modulation of the lateral growth of collagen type II fibrils. The sequence of protein collagen α1 is shown at the end of the application as “Collagen α1 amino acid sequence”. Known polymorphisms of this sequence are shown in Table 831.

  The following GO annotation applies to previously known proteins. The following annotations were found: Cartilage condensation, visual, auditory, cell-cell adhesion, extracellular matrix organization and biosynthesis, molecular function, which are annotations related to biological processes Annotations related to extracellular matrix structural proteins, extracellular matrix structural proteins, adhesion, and annotations related to cellular components: extracellular matrix, collagen, collagen type XI.

  GO assignments can be made at one or more http: // www. expasy. SwissProt / TremBl Protein knowledgebase available from ch / sprot / or http: // www. ncbi. nlm. nih. Depends on Locuslink available from gov / projects / LocusLink /.

  Cluster HUMCA1 XIA can be used as a diagnostic marker by overexpression of transcripts of this cluster in cancer. The expression of such transcripts in normal tissues is also shown by the method previously described. The term “number” in the right column of the table and the number on the y-axis of FIG. 32 refer to the weighted expression of ESTs in each category as “ppm” (the ppm of ESTs of a particular cluster in this category by ppm Ratio of expression to expression of all ESTs).

  In general, the following results were obtained, as shown for the histograms in FIG. This cluster was overexpressed (at least at minimal levels) in the following pathological conditions: malignant bone tumors, epithelial malignancies, a mixture of malignancies from different tissues, and lung malignancies.

  As mentioned above, cluster HUMCA1 XIA is characterized by the four transcripts listed in Table 1 above. These transcripts encode a protein which is a mutated form of the protein collagen α1. A description of each mutein of the invention is provided herein.

  The mutein HUMCA1XIA_P14 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript HUMCA1XIA_T16. An alignment to a known protein (collagen alpha 1) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between HUMCA1XIA_P14 and CA1B_HUMAN_V5 (SEQ ID NO: 1447) Corresponding to amino acids 1 to 1056 of CA1B_HUMAN_V5, corresponding to amino acids 1 to 1056 of HUMCA1XIA_P14 MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNSPEGISKTTGFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFSILFTVKPKKGIQSFLLSIYNEHGIQQIGVEVGRSPVFLFEDHTGKPAPEDYPLFRTVNIADGKWHRVAISVEKKTVTMIVDCKKKTTKPLDRSERAIVDTNGITVFGTRILDEEVFEGDIQQFLITGDPKAAYDYCEHYSPDCDSSAPKAAQAQEPQIDEYAPEDIIEYDYEYG AEYKEAESVTEGPTVTEETIAQTEANIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDSQRKNSEDTLYENKEIDGRDSDLLVDGDLGEYDFYEYKEYEDKPTSPPNEEFGPGVPAETDITETSINGHGAYGEKGQKGEPAVVEPGMLVEGPPGPAGPAGIMGPPGLQGPTGPPGDPGDRGPPGRPGLPGADGLPGPPGTMLMLPFRYGGDGSKGPTISAQEAQAQAILQQARIALRGPPGPMGLTGRPGPVGGPGSSGAKGESGDPGPQGPRGVQGPPGPTGKPGKRGRPGADGGRGMPGEPGAKGDRGFDGLPG PGDKGHRGERGPQGPPGPPGDDGMRGEDGEIGPRGLPGEAGPRGLLGPRGTPGAPGQPGMAGVDGPPGPKGNMGPQGEPGPPGQQGNPGPQGLPGPQGPIGPPGEKGPQGKPGLAGLPGADGPPGHPGKEGQSGEKGALGPPGPQGPIGYPGPRGVKGADGVRGLKGSKGEKGEDGFPGFKGDMGLKGDRGEVGQIGPRGEDGPEGPKGRAGPTGDPGPSGQAGEKGKLGVPGLPGYPGRQGPKGSTGFPGFPGANGEKGARGVAGKPGPRGQRGPTGPRGSRGARGPTGKPGPKGTSGGDGPPGPPGERGPQGPQGPVGFPGPKGPPGPPGK DGLPGHPGQRGETGFQ GKT GPPGP GV GPGP GV GPQGP GPT GETGPIP GERG GPP GE GE GLP GLP AG AG GA GA ア ミ ノ 酸 ア ミ ノ 酸 7〜 7〜 SM SM SM SM SM SM SM SM SM SM SM SM SM SM SM SM Comprises a second amino acid sequence which is at least 90%, most preferably at least 95% homologous, said first amino acid sequence and the second amino acid sequence being adjacent and in sequential order Isolated chimeric polypeptide coding HUMCA1XIA_P14.

  2. According to a preferred embodiment of the present invention, an isolated polypeptide encoding the tail of HUMCA1XIA_P14, comprising at least 70%, optionally at least about 80%, preferably at least about 85% of the sequence VSMMIINSQTIMVVNYSSSFITLML in HUMCA1XIA_P14 More preferably, provided is an isolated polypeptide encoding the tail of HUMCA1XIA_P14, comprising a polypeptide that is at least about 90%, most preferably at least about 95% homologous.

  It should be noted that the known protein sequence (CA1B_HUMAN) has one or more changes from the sequence shown at the end of the application and this amino acid sequence is named CA1B_HUMAN_V5. The occurrence of these changes was previously known and listed in the following table.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein HUMCA1XIA_P14 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows SNPs as shown in Table 835) It indicates whether it is known and the presence of a known SNP in the mutant protein HUMCA XIA P14 sequence supports the predicted sequence of this mutant protein of the invention).

  The mutein HUMCA1XIA_P14 is encoded by the following transcript: HUMCA1XIA_T16 (sequences shown at the end of the application). The coding part of the transcript HUMCA1XIA_T16 is shown in bold, starting from position 319 and ending at position 3561. The transcript also has the following SNPs listed in Table 836 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, the mutein HUMCA XIA P 14 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein HUMCA1XIA_P15 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript HUMCA1XIA_T17. An alignment to a known protein (collagen alpha 1) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between HUMCA1XIA_P15 and CA1B_HUMAN 1. Corresponding to amino acids 1 to 714 of CA1B_HUMAN, corresponding to amino acids 1 to 714 of HUMCA1XIA_P15 MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNSPEGISKTTGFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFSILFTVKPKKGIQSFLLSIYNEHGIQQIGVEVGRSPVFLFEDHTGKPAPEDYPLFRTVNIADGKWHRVAISVEKKTVTMIVDCKKKTTKPLDRSERAIVDTNGITVFGTRILDEEVFEGDIQQFLITGDPKAAYDYCEHYSPDCDSSAPKAAQAQEPQIDEYAPEDIIEYDYEYGEAEYK AESVTEGPTVTEETIAQTEANIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDSQRKNSEDTLYENKEIDGRDSDLLVDGDLGEYDFYEYKEYEDKPTSPPNEEFGPGVPAETDITETSINGHGAYGEKGQKGEPAVVEPGMLVEGPPGPAGPAGIMGPPGLQGPTGPPGDPGDRGPPGRPGLPGADGLPGPPGTMLMLPFRYGGDGSKGPTISAQEAQAQAILQQARIALRGPPGPMGLTGRPGPVGGPGSSGAKGESGDPGPQGPRGVQGPPGPTGKPGKRGRPGADGGRGMPGEPGAKGDRGFDGLPGLPGDK HRGERGPQGPPGPPGDDGMRGGEDGEIGPRGPLGAGPRGLPGOPGAPGQPGOGVDGPGPKGNMGPQGEPGPPQQGPGPGPLPGPIPGPEGP The first amino acid sequence at least 90% homologous to the GPMCIPGPGEGPGE and the sequence corresponding to the amino acids 715-729 of HUMCA XIA_P15 Comprises HUMCA1XIA_P15, comprising a second amino acid sequence which is at least 90%, most preferably at least 95% homologous, said first amino acid sequence and said second amino acid sequence being in a contiguous and consecutive order Isolated chimera Polypeptide.

  2. HUMCA1XIA_P15 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 90%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence MCCNLSFGILIPLQK in HUMCA1XIA_P15 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein HUMCA1XIA_P15 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows SNPs as shown in Table 837) It indicates whether it is known and the presence of a known SNP in the mutant protein HUMCA XIA P15 sequence supports the deduced sequence of this mutant protein according to the invention).

  The glycosylation sites of the mutant protein HUMCA1XIA_P15 compared to the known protein collagen α1 are shown in Table 838 (showing its position on the amino acid sequence in the first column, the second column has glycosylation sites in the mutant protein) Indicates if it is present, the last column indicates whether this position is different on the mutein).

  The mutein HUMCA1XIA_P15 is encoded by the following transcript: HUMCA1XIA_T17 (sequences shown at the end of the application). The coding part of the transcript HUMCA1XIA_T17 is shown in bold, starting from position 319 and ending at position 2505. The transcript also has the following SNPs listed in Table 839 (showing its position on the nucleotide sequence and listing another nucleic acid, the last column shows if the SNP is known, the mutein HUMCA1XIA_P15 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein HUMCA1XIA_P16 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript HUMCA1XIA_T19. An alignment to a known protein (collagen alpha 1) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between HUMCA1XIA_P16 and CA1B_HUMAN 1. Corresponding to amino acids 1 to 648 of CA1B_HUMAN, corresponding to amino acids 1 to 648 of HUMCA1XIA_P16 MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNSPEGISKTTGFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFSILFTVKPKKGIQSFLLSIYNEHGIQQIGVEVGRSPVFLFEDHTGKPAPEDYPLFRTVNIADGKWHRVAISVEKKTVTMIVDCKKKTTKPLDRSERAIVDTNGITVFGTRILDEEVFEGDIQQFLITGDPKAAYDYCEHYSPDCDSSAPKAAQAQEPQIDEYAPEDIIEYDYEYGEAEYK AESVTEGPTVTEETIAQTEANIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDSQRKNSEDTLYENKEIDGRDSDLLVDGDLGEYDFYEYKEYEDKPTSPPNEEFGPGVPAETDITETSINGHGAYGEKGQKGEPAVVEPGMLVEGPPGPAGPAGIMGPPGLQGPTGPPGDPGDRGPPGRPGLPGADGLPGPPGTMLMLPFRYGGDGSKGPTISAQEAQAQAILQQARIALRGPPGPMGLTGRPGPVGGPGSSGAKGESGDPGPQGPRGVQGPPGPTGKPGKRGRPGADGGRGMPGEPGAKGDRGFDGLPGLPGDK The first amino acid sequence that is at least 90% identical The polypeptide having the sequence VSFSFSLFYKKVIKFACDKRFVGRHDERKVV KLSLPLYLIYE corresponding to amino acids 697 to 739 and at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably A single encoding HUMCA1XIA_P16, comprising a third amino acid sequence which is at least 95% homologous, said first amino acid sequence, the second amino acid sequence and the third amino acid sequence being adjacent and in sequential order Detached chimeric polypeptide.

  2. Length “n” (wherein n is at least about 10 amino acids long, optionally at least about 20 amino acids long, preferably at least about 30 amino acids long, more preferably at least about 40 amino acids long, most preferably at least about 50 amino acids in length, at least two amino acids comprising AG, starting from any of the following structures: amino acid numbers 648-x-648, amino acid numbers 649 + ((n-2) -x) (formula An isolated chimeric polypeptide encoding an edge portion of HUMCA1XIA_P16, comprising a polypeptide having a sequence terminating in: x) varying from 0 to n-2).

  3. HUMCA1XIA_P16 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence VSFSFSLFYKKVIKFACDKRFVGRHDERKV VKLSLPLYLIY in HUMCA XIA P16 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein HUMCA1XIA_P16 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows SNPs as shown in Table 840) It indicates whether it is known, and the presence of a known SNP in the mutant protein HUMCA XIA P16 sequence supports the deduced sequence of this mutant protein of the invention).

  The glycosylation sites of the mutant protein HUMCA1XIA_P16 compared to the known protein collagen α1 are shown in Table 841 (showing its position on the amino acid sequence in the first column, the second column has glycosylation sites in the mutant protein) Indicates if it is present, the last column indicates whether this position is different on the mutein).

  The mutein HUMCA1XIA_P16 is encoded by the following transcript: HUMCA1XIA_T19 (sequences shown at the end of the application). The coding part of the transcript HUMCA1XIA_T19 is shown in bold, starting from position 319 and ending at position 2532. The transcript also has the following SNPs listed in Table 842 (indicating its position on the nucleotide sequence and listing another nucleic acid, the last column indicating whether the SNP is known, the mutein HUMCA1XIA_P16 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein HUMCA1XIA_P17 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript HUMCA1XIA_T20. An alignment to a known protein (collagen alpha 1) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between HUMCA1XIA_P17 and CA1B_HUMAN 1. Corresponding to amino acids 1-260 of CA1B_HUMAN, at least 90% homologous first amino acid and the corresponding MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNSPEGISKTTGFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFSILFTVKPKKGIQSFLLSIYNEHGIQQIGVEVGRSPVFLFEDHTGKPAPEDYPLFRTVNIADGKWHRVAISVEKKTVTMIVDCKKKTTKPLDRSERAIVDTNGITVFGTRILDEEVFEGDIQQFLITGDPKAAYDYCEHYSPDCDSSAPKAAQAQEPQIDE to amino acids 1-260 of HUMCA1XIA_P17 And at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95%, and a polypeptide having the sequence VRSTRPEKVFVFQ corresponding to amino acids 261 to 273 of HUMCA1XIA_P17 An isolated chimeric polypeptide encoding HUMCA1XIA_P17, which comprises the homologous second amino acid sequence, said first amino acid sequence and the second amino acid sequence being adjacent and in sequential order.

  2. HUMCA1XIA_P17 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence VRSTRPEKVFVF in HUMCA1XIA_P17 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein HUMCA1XIA_P17 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows SNPs as shown in Table 843) It indicates whether it is known, and the presence of a known SNP in the mutant protein HUMCA XIA P 17 sequence supports the predicted sequence of this mutant protein of the invention).

  The glycosylation sites of the mutant protein HUMCA1XIA_P17 compared to the known protein collagen α1 are shown in Table 844 (showing its position on the amino acid sequence in the first column, the second column has glycosylation sites in the mutant protein) Indicates if it is present, the last column indicates whether this position is different on the mutein).

  The mutein HUMCA1XIA_P17 is encoded by the following transcript: HUMCA1XIA_T20 (sequences shown at the end of the application). The coding part of the transcript HUMCA1XIA_T20 is shown in bold, starting from position 319 and ending at position 1137. The transcript also has the following SNPs listed in Table 845 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, the mutein HUMCA XIA P 17 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  As mentioned above, cluster HUMCA1XIA is characterized by the 46 segments listed in Table 2 above, the sequences of which are shown at the end of the application. These segments are part of the nucleic acid sequence, which are of particular interest and are individually described herein. A description of each segment of the invention is provided herein.

  The segment cluster HUMCA1XIA_node_0 of the present invention is supported by 13 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMCA1XIA_T16, HUMCA1XIA_T17, HUMCA1XIA_T19, and HUMCA1XIA_T20. Table 846 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCA1XIA_node_2 of the present invention is supported by nine libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMCA1XIA_T16, HUMCA1XIA_T17, HUMCA1XIA_T19, and HUMCA1XIA_T20. Table 847 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCA1XIA_node_4 of the present invention is supported by 5 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMCA1XIA_T16, HUMCA1XIA_T17, HUMCA1XIA_T19, and HUMCA1XIA_T20. Table 848 below describes the start and end positions of this segment on each transcript.

  Microarray (chip) data for this segment is also available, as follows. As described above, with respect to the clusters themselves, different oligonucleotides were tested for differential expression in different disease states, in particular cancer. The following oligonucleotides were found to reach this segment (for lung cancer) (shown in Table 849).

  The segment cluster HUMCA1XIA_node_6 of the present invention is supported by 5 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMCA1XIA_T16, HUMCA1XIA_T17, HUMCA1XIA_T19, and HUMCA1XIA_T20. Table 850 below describes the start and end positions of this segment on each transcript.

  Microarray (chip) data for this segment is also available, as follows. As described above, with respect to the clusters themselves, different oligonucleotides were tested for differential expression in different disease states, in particular cancer. The following oligonucleotides were found to reach this segment (for lung cancer) (shown in Table 851).

  The segment cluster HUMCA1XIA_node_8 of the present invention is supported by 5 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMCA1XIA_T16, HUMCA1XIA_T17, HUMCA1XIA_T19, and HUMCA1XIA_T20. Table 852 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCA1XIA_node_9 of the present invention is supported by two libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMCA1XIA_T20. Table 853 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCA1XIA_node_18 of the present invention is supported by six libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMCA1XIA_T16, HUMCA1XIA_T17, and HUMCA1XIA_T19. Table 854 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCA1XIA_node_54 of the present invention is supported by two libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMCA1XIA_T19. Table 855 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCA1XIA_node_55 of the present invention is supported by 4 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMCA1XIA_T17 and HUMCA1XIA_T19. Table 856 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCA1XIA_node_92 of the present invention is supported by two libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMCA1XIA_T16. Table 857 below describes the start and end positions of this segment on each transcript.

  According to an optional embodiment of the present invention, there is also provided a short segment associated with the above cluster. These segments are up to about 120 bp in length and are therefore included in the individual descriptions.

  The segment cluster HUMCA1XIA_node_11 of the present invention is supported by three libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMCA1XIA_T16, HUMCA1XIA_T17, and HUMCA1XIA_T19. Table 858 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCA1XIA_node_15 of the present invention is supported by 5 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMCA1XIA_T16, HUMCA1XIA_T17, and HUMCA1XIA_T19. Table 859 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCA1XIA_node_19 of the present invention is supported by 3 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMCA1XIA_T16, HUMCA1XIA_T17, and HUMCA1XIA_T19. Table 860 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCA1XIA_node_21 of the present invention is supported by two libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMCA1XIA_T16, HUMCA1XIA_T17, and HUMCA1XIA_T19. Table 861 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCA1XIA_node_23 of the present invention is supported by three libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMCA1XIA_T16, HUMCA1XIA_T17, and HUMCA1XIA_T19. Table 862 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCA1XIA_node_25 of the present invention is supported by three libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMCA1XIA_T16, HUMCA1XIA_T17, and HUMCA1XIA_T19. Table 863 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCA1XIA_node_27 of the present invention is supported by two libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMCA1XIA_T16, HUMCA1XIA_T17, and HUMCA1XIA_T19. Table 864 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCA1XIA_node_29 of the present invention is supported by 3 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMCA1XIA_T16, HUMCA1XIA_T17, and HUMCA1XIA_T19. Table 865 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCA1XIA_node_31 of the present invention is supported by three libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMCA1XIA_T16, HUMCA1XIA_T17, and HUMCA1XIA_T19. Table 866 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCA1XIA_node_33 of the present invention is supported by three libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMCA1XIA_T16, HUMCA1XIA_T17, and HUMCA1XIA_T19. Table 867 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCA1XIA_node_35 of the present invention is supported by 4 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMCA1XIA_T16, HUMCA1XIA_T17, and HUMCA1XIA_T19. Table 868 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCA1XIA_node_37 of the present invention is supported by 4 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMCA1XIA_T16, HUMCA1XIA_T17, and HUMCA1XIA_T19. Table 869 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCA1XIA_node_39 of the present invention is supported by 5 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMCA1XIA_T16, HUMCA1XIA_T17, and HUMCA1XIA_T19. Table 870 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCA1XIA_node_41 of the present invention is supported by 4 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMCA1XIA_T16, HUMCA1XIA_T17, and HUMCA1XIA_T19. Table 871 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCA1XIA_node_43 of the present invention is supported by 5 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMCA1XIA_T16, HUMCA1XIA_T17, and HUMCA1XIA_T19. Table 872 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCA1XIA_node_45 of the present invention is supported by 4 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMCA1XIA_T16 and HUMCA1XIA_T17. Table 873 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCA1XIA_node_47 of the present invention is supported by 5 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMCA1XIA_T16, HUMCA1XIA_T17, and HUMCA1XIA_T19. Table 874 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCA1XIA_node_49 of the present invention is supported by 5 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMCA1XIA_T16, HUMCA1XIA_T17, and HUMCA1XIA_T19. Table 875 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCA1XIA_node_51 of the present invention is supported by seven libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMCA1XIA_T16, HUMCA1XIA_T17, and HUMCA1XIA_T19. Table 876 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCA1XIA_node_57 of the present invention is supported by 4 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMCA1XIA_T16. Table 877 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCA1XIA_node_59 of the present invention is supported by three libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMCA1XIA_T16. Table 878 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCA1XIA_node_62 of the present invention is supported by three libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMCA1XIA_T16. Table 879 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCA1XIA_node_64 of the present invention is supported by 4 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMCA1XIA_T16. Table 880 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCA1XIA_node_66 of the present invention is supported by 4 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMCA1XIA_T16. Table 881 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCA1XIA_node_68 of the present invention is supported by seven libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMCA1XIA_T16. Table 88 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCA1XIA_node_70 of the present invention is supported by six libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMCA1XIA_T16. Table 883 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCA1XIA_node_72 of the present invention is supported by six libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMCA1XIA_T16. Table 884 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCA1XIA_node_74 of the present invention is supported by 5 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMCA1XIA_T16. Table 885 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCA1XIA_node_76 of the present invention is supported by six libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMCA1XIA_T16. Table 886 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCA1XIA_node_78 of the present invention is supported by six libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMCA1XIA_T16. Table 887 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCA1XIA_node_81 of the present invention is supported by eight libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMCA1XIA_T16. Table 888 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCA1XIA_node_83 of the present invention is supported by seven libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMCA1XIA_T16. Table 889 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCA1XIA_node_85 of the present invention is supported by six libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMCA1XIA_T16. Table 890 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCA1XIA_node_87 of the present invention is supported by 10 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMCA1XIA_T16. Table 891 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCA1XIA_node_89 of the present invention is supported by nine libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMCA1XIA_T16. Table 892, below, lists the start and end positions of this segment on each transcript.

  The segment cluster HUMCA1XIA_node_91 of the present invention is supported by 11 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMCA1XIA_T16. Table 893 below describes the start and end positions of this segment on each transcript.

Mutated protein alignment against previously known proteins:
Sequence name: CA1B_HUMAN_V5

Sequence documentation:

Alignment of: HUMCA1XIA_P14 x CA1B_HUMAN_V5 ..

Alignment segment 1/1:

Quality: 10456.00 Escore: 0
Matching length: 1058 Total length: 1058
Matching Percent Similarity: 99.91 Matching Percent Identity: 99.91
Total Percent Similarity: 99.91 Total Percent Identity: 99.91
Gaps: 0

Alignment:
....
1 MEPWSSRMWTKRWRWDFTVTTLALTFLTFAREVRGAPVDVLKALDFNS 50
||||||||||||||||||||||||||||||||||||||||
1 MEPWSSRMWTKRWRWDFTVTTLALTFLTFAREVRGAPVDVLKALDFNS 50
....
51 PEGISKTTGFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFS 100
||||||||||||||||||||||||||||||||||||||||
51 PEGISKTTGFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFS 100
....
101 ILFTVKKPKKGIQSFLLSIYNEHGGIQQIGVEVGRSPFLFEDHTGKPAPED 150
||||||||||||||||||||||||||||||||||||||||
101 ILFTVKKPKKGIQSFLLSIYNEHGGIQQIGVEVGRSPFLFEDHTGKPAPED 150
....
151 YPLFRTVNIADGKWHRVAISVEKKTVTM IVDCKKKTTKPLDRSERAIVDT 200
||||||||||||||||||||||||||||||||||||||||
151 YPLFRTVNIADGKWHRVAISVEKKTVTM IVDCKKKTTKPLDRSERAIVDT 200
....
201 NGITVFGTRILDEEVFEGDI QQ FLITGDPKAAYDYCEHY SPDCDSSAPKA 250
||||||||||||||||||||||||||||||||||||||||
201 NGITVFGTRILDEEVFEGDI QQ FLITGDPKAAYDYCEHY SPDCDSSAPKA 250
....
251 AQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVTEGPTVTEETIAQTEA 300
||||||||||||||||||||||||||||||||||||||||
251 AQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVTEGPTVTEETIAQTEA 300
....
301 NIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDS 350
||||||||||||||||||||||||||||||||||||||||
301 NIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDS 350
....
351 QRKNSEDTLYENKEIDGRD SDLLVDDDLGEYDFYEYKEYEDKPTSPPNEE 400
||||||||||||||||||||||||||||||||||||||||
351 QRKNSEDTLYENKEIDGRD SDLLVDDDLGEYDFYEYKEYEDKPTSPPNEE 400
....
401 FGPGVPAETDITETSINGHGAYGEKGQ KGEPAV VEPGMLVEGPPGPAGPA 450
||||||||||||||||||||||||||||||||||||||||
401 FGPGVPAETDITETSINGHGAYGEKGQ KGEPAV VEPGMLVEGPPGPAGPA 450
....
451 GIMGPPGLQGPTPGPPGDPRGDRGPP GRPGPLGGAPGLPGPPGTMLMPFRYG 500
||||||||||||||||||||||||||||||||||||||||
451 GIMGPPGLQGPTPGPPGDPRGDRGPP GRPGPLGGAPGLPGPPGTMLMPFRYG 500
....
501 GDGSKGPPTISAQEAAQAILQQARIALLRGPPGPMGLTGRPGPVGGPGSSG 550
||||||||||||||||||||||||||||||||||||||||
501 GDGSKGPPTISAQEAAQAILQQARIALLRGPPGPMGLTGRPGPVGGPGSSG 550
....
551 AKGESGDPGPQGPRGVQGPPGPTGKPGKRGRPGADGGRGMPGEPGA GDR 600
||||||||||||||||||||||||||||||||||||||||
551 AKGESGDPGPQGPRGVQGPPGPTGKPGKRGRPGADGGRGMPGEPGA GDR 600
....
601 G FDGDL GLP GPG DKG HR GER GP QGPP GPP G D D G MRG EDGE IGPR GI PGE AGP 650
||||||||||||||||||||||||||||||||||||||||
601 G FDGDL GLP GPG DKG HR GER GP QGPP GPP G D D G MRG EDGE IGPR GI PGE AGP 650
....
651 RGLLGPRGTPGAPGQPGMAGVDGPPGPKGNMGPQGEPGPPGQQGNPGPQG 700
||||||||||||||||||||||||||||||||||||||||
651 RGLLGPRGTPGAPGQPGMAGVDGPPGPKGNMGPQGEPGPPGQQGNPGPQG 700
....
701 LPGPQGPIGPPGEKGPQGGPGLAGLPGADGPPGHPGKEGQSGEKGALGPP 750
||||||||||||||||||||||||||||||||||||||||
701 LPGPQGPIGPPGEKGPQGGPGLAGLPGADGPPGHPGKEGQSGEKGALGPP 750
....
751 GPQGPIGGPGPRGVGGADGGVRGLKGSKGEKGEDGFPGFKGDMGLKGDRGE 800
||||||||||||||||||||||||||||||||||||||||
751 GPQGPIGGPGPRGVGGADGGVRGLKGSKGEKGEDGFPGFKGDMGLKGDRGE 800
....
801 VGQIGPRGEDGPEGPGRAGPTGPGPSPGQAGEKGKLPGPGPGYPGRQG 850
||||||||||||||||||||||||||||||||||||||||
801 VGQIGPRGEDGPEGPGRAGPTGPGPSPGQAGEKGKLPGPGPGYPGRQG 850
....
851 PKGSTGFPFFPGANGEKGARGV AG KP GPRG Q RGPTGPRGS RG ARGPTGKP 900
||||||||||||||||||||||||||||||||||||||||
851 PKGSTGFPFFPGANGEKGARGV AG KP GPRG Q RGPTGPRGS RG ARGPTGKP 900
....
901 GPKGTSGGDGPPGPP GERGPQ GPGPGPGFPGPGPGPPGPRGPGLPGHPGQ 950
||||||||||||||||||||||||||||||||||||||||
901 GPKGTSGGDGPPGPP GERGPQ GPGPGPGFPGPGPGPPGPRGPGLPGHPGQ 950
....
951 RGETGFQGKTGPPGPGGVVGPQGPPTGETGPIGERGHPGPPGPPGEQGLPG 1000
||||||||||||||||||||||||||||||||||||||||
951 RGETGFQGKTGPPGPGGVVGPQGPPTGETGPIGERGHPGPPGPPGEQGLPG 1000
....
1001 AAGKEGAKGDPGPQGISGKDGPAGLRGFPGERGLPGAQGAPGLKGGEGPQ 1050
||||||||||||||||||||||||||||||||||||||||
1001 AAGKEGAKGDPGPQGISGKDGPAGLRGFPGERGLPGAQGAPGLKGGEGPQ 1050

1051 GPPGPVVS 1058
||||||
1051 GPPGP VGS 1058






Sequence name: CA1B_HUMAN

Sequence documentation:

Alignment of: HUMCA1XIA_P15 x CA1B_HUMAN ..

Alignment segment 1/1:

Quality: 7073.00 Escore: 0
Matching length: 714 Total length: 714
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MEPWSSRMWTKRWRWDFTVTTLALTFLTFAREVRGAPVDVLKALDFNS 50
||||||||||||||||||||||||||||||||||||||||
1 MEPWSSRMWTKRWRWDFTVTTLALTFLTFAREVRGAPVDVLKALDFNS 50
....
51 PEGISKTTGFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFS 100
||||||||||||||||||||||||||||||||||||||||
51 PEGISKTTGFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFS 100
....
101 ILFTVKKPKKGIQSFLLSIYNEHGGIQQIGVEVGRSPFLFEDHTGKPAPED 150
||||||||||||||||||||||||||||||||||||||||
101 ILFTVKKPKKGIQSFLLSIYNEHGGIQQIGVEVGRSPFLFEDHTGKPAPED 150
....
151 YPLFRTVNIADGKWHRVAISVEKKTVTM IVDCKKKTTKPLDRSERAIVDT 200
||||||||||||||||||||||||||||||||||||||||
151 YPLFRTVNIADGKWHRVAISVEKKTVTM IVDCKKKTTKPLDRSERAIVDT 200
....
201 NGITVFGTRILDEEVFEGDI QQ FLITGDPKAAYDYCEHY SPDCDSSAPKA 250
||||||||||||||||||||||||||||||||||||||||
201 NGITVFGTRILDEEVFEGDI QQ FLITGDPKAAYDYCEHY SPDCDSSAPKA 250
....
251 AQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVTEGPTVTEETIAQTEA 300
||||||||||||||||||||||||||||||||||||||||
251 AQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVTEGPTVTEETIAQTEA 300
....
301 NIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDS 350
||||||||||||||||||||||||||||||||||||||||
301 NIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDS 350
....
351 QRKNSEDTLYENKEIDGRD SDLLVDDDLGEYDFYEYKEYEDKPTSPPNEE 400
||||||||||||||||||||||||||||||||||||||||
351 QRKNSEDTLYENKEIDGRD SDLLVDDDLGEYDFYEYKEYEDKPTSPPNEE 400
....
401 FGPGVPAETDITETSINGHGAYGEKGQ KGEPAV VEPGMLVEGPPGPAGPA 450
||||||||||||||||||||||||||||||||||||||||
401 FGPGVPAETDITETSINGHGAYGEKGQ KGEPAV VEPGMLVEGPPGPAGPA 450
....
451 GIMGPPGLQGPTPGPPGDPRGDRGPP GRPGPLGGAPGLPGPPGTMLMPFRYG 500
||||||||||||||||||||||||||||||||||||||||
451 GIMGPPGLQGPTPGPPGDPRGDRGPP GRPGPLGGAPGLPGPPGTMLMPFRYG 500
....
501 GDGSKGPPTISAQEAAQAILQQARIALLRGPPGPMGLTGRPGPVGGPGSSG 550
||||||||||||||||||||||||||||||||||||||||
501 GDGSKGPPTISAQEAAQAILQQARIALLRGPPGPMGLTGRPGPVGGPGSSG 550
....
551 AKGESGDPGPQGPRGVQGPPGPTGKPGKRGRPGADGGRGMPGEPGA GDR 600
||||||||||||||||||||||||||||||||||||||||
551 AKGESGDPGPQGPRGVQGPPGPTGKPGKRGRPGADGGRGMPGEPGA GDR 600
....
601 G FDGDL GLP GPG DKG HR GER GP QGPP GPP G D D G MRG EDGE IGPR GI PGE AGP 650
||||||||||||||||||||||||||||||||||||||||
601 G FDGDL GLP GPG DKG HR GER GP QGPP GPP G D D G MRG EDGE IGPR GI PGE AGP 650
....
651 RGLLGPRGTPGAPGQPGMAGVDGPPGPKGNMGPQGEPGPPGQQGNPGPQG 700
||||||||||||||||||||||||||||||||||||||||
651 RGLLGPRGTPGAPGQPGMAGVDGPPGPKGNMGPQGEPGPPGQQGNPGPQG 700
.
701 LPGPQGPIGPPGEK 714
|||||||||||||
701 LPGPQGPIGPPGEK 714






Sequence name: CA1B_HUMAN

Sequence documentation:

Alignment of: HUMCA1XIA_P16 x CA1B_HUMAN ..

Alignment segment 1/1:

Quality: 6795.00 Escore: 0
Matching length: 696 Total length: 714
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 97.48 Total Percent Identity: 97.48
Gaps: 1

Alignment:
....
1 MEPWSSRMWTKRWRWDFTVTTLALTFLTFAREVRGAPVDVLKALDFNS 50
||||||||||||||||||||||||||||||||||||||||
1 MEPWSSRMWTKRWRWDFTVTTLALTFLTFAREVRGAPVDVLKALDFNS 50
....
51 PEGISKTTGFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFS 100
||||||||||||||||||||||||||||||||||||||||
51 PEGISKTTGFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFS 100
....
101 ILFTVKKPKKGIQSFLLSIYNEHGGIQQIGVEVGRSPFLFEDHTGKPAPED 150
||||||||||||||||||||||||||||||||||||||||
101 ILFTVKKPKKGIQSFLLSIYNEHGGIQQIGVEVGRSPFLFEDHTGKPAPED 150
....
151 YPLFRTVNIADGKWHRVAISVEKKTVTM IVDCKKKTTKPLDRSERAIVDT 200
||||||||||||||||||||||||||||||||||||||||
151 YPLFRTVNIADGKWHRVAISVEKKTVTM IVDCKKKTTKPLDRSERAIVDT 200
....
201 NGITVFGTRILDEEVFEGDI QQ FLITGDPKAAYDYCEHY SPDCDSSAPKA 250
||||||||||||||||||||||||||||||||||||||||
201 NGITVFGTRILDEEVFEGDI QQ FLITGDPKAAYDYCEHY SPDCDSSAPKA 250
....
251 AQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVTEGPTVTEETIAQTEA 300
||||||||||||||||||||||||||||||||||||||||
251 AQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVTEGPTVTEETIAQTEA 300
....
301 NIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDS 350
||||||||||||||||||||||||||||||||||||||||
301 NIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDS 350
....
351 QRKNSEDTLYENKEIDGRD SDLLVDDDLGEYDFYEYKEYEDKPTSPPNEE 400
||||||||||||||||||||||||||||||||||||||||
351 QRKNSEDTLYENKEIDGRD SDLLVDDDLGEYDFYEYKEYEDKPTSPPNEE 400
....
401 FGPGVPAETDITETSINGHGAYGEKGQ KGEPAV VEPGMLVEGPPGPAGPA 450
||||||||||||||||||||||||||||||||||||||||
401 FGPGVPAETDITETSINGHGAYGEKGQ KGEPAV VEPGMLVEGPPGPAGPA 450
....
451 GIMGPPGLQGPTPGPPGDPRGDRGPP GRPGPLGGAPGLPGPPGTMLMPFRYG 500
||||||||||||||||||||||||||||||||||||||||
451 GIMGPPGLQGPTPGPPGDPRGDRGPP GRPGPLGGAPGLPGPPGTMLMPFRYG 500
....
501 GDGSKGPPTISAQEAAQAILQQARIALLRGPPGPMGLTGRPGPVGGPGSSG 550
||||||||||||||||||||||||||||||||||||||||
501 GDGSKGPPTISAQEAAQAILQQARIALLRGPPGPMGLTGRPGPVGGPGSSG 550
....
551 AKGESGDPGPQGPRGVQGPPGPTGKPGKRGRPGADGGRGMPGEPGA GDR 600
||||||||||||||||||||||||||||||||||||||||
551 AKGESGDPGPQGPRGVQGPPGPTGKPGKRGRPGADGGRGMPGEPGA GDR 600
....
601 G FDGPGLPGPGDKGHRGERGPQGPPGPPGDDGMRGEDGEIGPRGPGEA .. 648
|||||||||||||||||||||||||||||||||||||||
601 G FDGDL GLP GPG DKG HR GER GP QGPP GPP G D D G MRG EDGE IGPR GI PGE AGP 650
....
649 ..... GMAG VDGPP GPKGNMGPQGEPGPP GQQ GNPGPQG 682
|||||||||||||||||||||||||||||||
651 RGLLGPRGTPGAPGQPGMAGVDGPPGPKGNMGPQGEPGPPGQQGNPGPQG 700
.
683 LPGPQGPIGPPGEK 696
|||||||||||||
701 LPGPQGPIGPPGEK 714






Sequence name: CA1B_HUMAN

Sequence documentation:

Alignment of: HUMCA1XIA_P17 x CA1B_HUMAN ..

Alignment segment 1/1:

Quality: 2561.00 Escore: 0
Matching length: 260 Total length: 260
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MEPWSSRMWTKRWRWDFTVTTLALTFLTFAREVRGAPVDVLKALDFNS 50
||||||||||||||||||||||||||||||||||||||||
1 MEPWSSRMWTKRWRWDFTVTTLALTFLTFAREVRGAPVDVLKALDFNS 50
....
51 PEGISKTTGFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFS 100
||||||||||||||||||||||||||||||||||||||||
51 PEGISKTTGFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFS 100
....
101 ILFTVKKPKKGIQSFLLSIYNEHGGIQQIGVEVGRSPFLFEDHTGKPAPED 150
||||||||||||||||||||||||||||||||||||||||
101 ILFTVKKPKKGIQSFLLSIYNEHGGIQQIGVEVGRSPFLFEDHTGKPAPED 150
....
151 YPLFRTVNIADGKWHRVAISVEKKTVTM IVDCKKKTTKPLDRSERAIVDT 200
||||||||||||||||||||||||||||||||||||||||
151 YPLFRTVNIADGKWHRVAISVEKKTVTM IVDCKKKTTKPLDRSERAIVDT 200
....
201 NGITVFGTRILDEEVFEGDI QQ FLITGDPKAAYDYCEHY SPDCDSSAPKA 250
||||||||||||||||||||||||||||||||||||||||
201 NGITVFGTRILDEEVFEGDI QQ FLITGDPKAAYDYCEHY SPDCDSSAPKA 250
.
251 AQAQEPQIDE 260
||||||||||
251 AQAQEPQIDE 260

Expression of homo-Sapiens collagen type XI α1 (COL11A1) HUMCA1XIA transcript detectable by the amplicon shown in sequence name HUMCA1X1Aseg55 in normal and cancerous lung tissue seg55, HUMCA1X1Aseg55 amplicon (SEQ ID NO: 1663) 1661) and the expression of homo-Sapiens collagen type XI α1 (COL11A1) transcripts detectable by HUMCA 1 × 1 Aseg 55 R (SEQ ID NO: 1662) was measured by real-time PCR. In parallel, four housekeeping genes-PBGD (GenBank Accession No. BC019323, Amplicon – PBGD-Amplicon, SEQ ID No. 334), HPRT1 (GenBank Accession No. NM_000194, Amplicon – HPRT1- Amplicons, SEQ ID NO: 1297), Ubiquitin (GenBank Accession No. BC000449, Amplicon – Ubiquitin-Amplicon SEQ ID NO: 328), and SDHA (GenBank Accession No. NM_004168, Amplicon – SDHA-Amplicon SEQ ID NO: 331) was similarly measured. For each RT sample, the expression of the amplicon was normalized to the geometric mean of the housekeeping gene dose. Normalized PM samples by dividing the normalized volume of each RT sample by the median volume of normal postmortem (PM) samples (sample numbers 47-50, 90-93, 96-99, Table 2 above) Magnifications of upregulation of each sample to the median of were obtained.

  FIG. 67 is a histogram showing over expression of the homo-Sapiens collagen type XI α1 (COL11A1) transcript in cancerous lung samples compared to normal samples. Values represent the average of duplicate experiments. Error bars indicate the obtained minimum and maximum values.

  As evident from FIG. 67, the expression of homo-Sapiens collagen type XI α1 (COL11A1) transcripts detectable by the above amplicon in a cancer sample is a non-cancerous sample (sample numbers 47-50, 90-93, Significantly higher than 96-99, Table 2). Apparently, at least 5-fold overexpression was found in 11 out of 15 adenocarcinoma samples, 11 out of 16 squamous cell carcinoma samples, and 2 out of 4 large cell carcinoma samples. It was done.

  Primer pairs are also optionally and preferably included within the scope of the present invention, for example, in the above experiments the following primers were used only as a non-limiting illustration of suitable primer pairs: HUMCA1X1Aseg55F forward primer and HUMCA1X1Aseg55R reverse Direction primer.

  The present invention also preferably includes any amplicon obtained by use of any suitable primer pair (e.g. in the above experiments) and obtained the following amplicons only as a non-limiting illustration of a suitable amplicon : HUMCA 1 X 1 Aseg 55.

Forward primer-HUMCA1X1Aseg55F (SEQ ID NO: 1661): TTCTCATAGTATTCCATTGATTGGGTA
Reverse primer-HUMCA1X1Aseg55R (SEQ ID NO: 1662): CACCGGTATGGAGAATAGCGA
Amplicon (SEQ ID NO: 1663): TTCTCATAGTATTCCATTGATTGGGGTATACAGGTTCTGTTTACTTTTACTTGGCAGTTGATAGAATAGGTGTAGTTTATACTTTTTCGCTATTCTCCATACCGGTG

Description of Cluster T11628 Cluster T11628 is characterized by 6 transcripts and 25 segments of interest, the names of which are shown in Tables 894 and 895 respectively, and the sequence itself is shown at the end of the application. Selected protein variants are shown in Table 896.

  These sequences are variants of the known protein myoglobin (SwissProt accession identifier MYG_HUMAN) (SEQ ID NO: 1448), which has been referred to herein as a previously known protein.

  The protein myoglobin is known or considered to have the following function: it acts as a counter-supply of oxygen and promotes the transfer of oxygen in muscle. The sequence of the protein myoglobin is shown at the end of the application as "myoglobin amino acid sequence". Known polymorphisms of this sequence are shown in Table 897.

  As mentioned above, cluster T11628 is characterized by the six transcripts listed in Table 1 above. These transcripts encode a protein which is a mutated form of the protein myoglobin. A description of each mutein of the invention is provided herein.

  The mutein T11628_PEA_1_P2 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript T11628_PEA_1_T3. An alignment to a known protein (myoglobin) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report on comparison between T11628_PEA_1_P2 and Q8WVH6 (SEQ ID NO: 1450) At least 70%, optionally at least 80%, preferably at least 85%, preferably at least 90%, more preferably at least 90%, most preferably at least 95% homologous to the polypeptide having the sequence MGLSDGEWQLVLNVWGKVEADIPGHGQEVLIRLFKGHPETLEKDFDKFKHLKSEDE corresponding to amino acids 1-55 of T11628_PEA_1_P2 1 and corresponding to amino acids 1 to 99 of Q8WVH6 and also to amino acids 56 to 154 of T11628_PEA_1_P2 MKASEDLKKHGATVLTGLGKKKKHHEAEIKPLAQSHATKHKIPVKYLEFISECIIQVLQSKHPGDFGADAQGAMNKALELFRKDMASNYKELGFQG and And a Kutomo 90% homologous second amino acid sequence, the first amino acid sequence and a second amino acid sequence, contiguous and in sequential order, the isolated chimeric polypeptide coding T11628_PEA_1_P2.

  2. The sequence of T11628_PEA_1_P2 at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence An isolated polypeptide encoding

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: Intracellular. Protein localization is considered to be intracellular as no transmembrane domain estimation program will deduce that this protein is a transmembrane domain. Furthermore, both signal peptide deducing programs deduce that this protein is a non-secretory protein.

  The mutein T11628_PEA_1_P2 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows SNPs as shown in Table 898) It is indicated whether it is known and the presence of a known SNP in the mutein T11628_PEA_1_P2 sequence supports the putative sequence of this mutein of the invention).

  The mutein T11628_PEA_1_P2 is encoded by the following transcript: T11628_PEA_1_T3 (sequences shown at the end of the application). The coding portion of the transcript T11628_PEA_1_T3 is shown in bold, starting from position 220 and ending at position 681. The transcript also has the following SNPs listed in Table 899 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein T11628_PEA_1_P2 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein T11628_PEA_1_P5 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript T11628_PEA_1_T9. An alignment to a known protein (myoglobin) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of the comparison between T11628_PEA_1_P5 and MYG_HUMAN_V1 (SEQ ID NO: 1449) A member of the invention is a peptide comprising a member of

  It should be noted that the known protein sequence (MYG_HUMAN) has one or more changes from the sequence shown at the end of the application and this amino acid sequence is designated as MYG_HUMAN_V1. The occurrence of these changes was previously known and listed in the following table.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: Intracellular. Protein localization is considered to be intracellular as no transmembrane domain estimation program will deduce that this protein is a transmembrane domain. Furthermore, both signal peptide deducing programs deduce that this protein is a non-secretory protein.

  The mutein T11628_PEA_1_P5 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing the other amino acids, and listing the other amino acids, as shown in Table 901), and the last column is the SNP It is shown whether it is known and the presence of a known SNP in the mutein T11628_PEA_1_P5 sequence supports the putative sequence of this mutein of the invention).

  The mutein T11628_PEA_1_P5 is encoded by the following transcript: T11628_PEA_1_T9 (sequences shown at the end of the application). The code portion of transcript T11628_PEA_1_T9 is shown in bold, starting at position 211 and ending at position 507. The transcript also has the following SNPs listed in Table 902 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein T11628_PEA_1_P5 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein T11628_PEA_1_P7 according to the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript T11628_PEA_1_T11. An alignment to a known protein (myoglobin) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between T11628_PEA_1_P7 and MYG_HUMAN_V1. MGL DGWE corresponding to amino acid 1 to 134 of MYG_HUMAN_V1 and T11628 _PEA_1_P7 as a UH 7 At least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous And a second amino acid sequence, the first amino acid sequence and a second amino acid sequence, contiguous and in sequential order, the isolated chimeric polypeptide coding T11628_PEA_1_P7.

  It should be noted that the known protein sequence (MYG_HUMAN) has one or more changes from the sequence shown at the end of the application and this amino acid sequence is designated as MYG_HUMAN_V1. The occurrence of these changes was previously known and listed in the following table.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: Intracellular. Protein localization is considered to be intracellular as no transmembrane domain estimation program will deduce that this protein is a transmembrane domain. Furthermore, both signal peptide deducing programs deduce that this protein is a non-secretory protein.

  The mutein T11628_PEA_1_P7 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows SNPs as shown in Table 904) It is shown whether it is known and the presence of a known SNP in the mutein T11628_PEA_1_P7 sequence supports the putative sequence of this mutein of the invention).

  The mutein T11628_PEA_1_P7 is encoded by the following transcript: T11628_PEA_1_T11 (sequences shown at the end of the application). The code portion of the transcript T11628_PEA_1_T11 is shown in bold, starting from position 319 and ending at position 723. The transcript also has the following SNPs listed in Table 905 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein T11628_PEA_1_P7 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein T11628_PEA_1_P10 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript T11628_PEA_1_T4. An alignment to a known protein (myoglobin) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report on comparison between T11628_PEA_1_P10 and Q8WVH6 (SEQ ID NO: 1450) At least 70%, optionally at least 80%, preferably at least 85%, preferably at least 90%, more preferably at least 90%, most preferably at least 95% homologous to a polypeptide having the sequence MGLSDGEWQLVLNVWGKVEADIPGHGQEVLIRLFKGHPETLEKDFFKHLKSEDE corresponding to amino acids 1-55 of T11628_PEA_1_P10 1 and corresponding to amino acids 1 to 99 of Q8WVH6 and to amino acids 56 to 154 of T11628_PEA_1_P10, MKASEDLKKHGATVLTGLGKKKKHHEAEIKPLAQSHATKHKIPVKYLEFISECIIQVLQSKHPGDFGADAQGAMNKALELFRKDDMASNYKELGFQG And at least 90% homologous to a second amino acid sequence, the first amino acid sequence and a second amino acid sequence, contiguous and in sequential order, the isolated chimeric polypeptide coding T11628_PEA_1_P10.

  2. T11628_PEA_1_P10 comprising a polypeptide of at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to TMG An isolated polypeptide encoding

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: Intracellular. Protein localization is considered to be intracellular as no transmembrane domain estimation program will deduce that this protein is a transmembrane domain. Furthermore, both signal peptide deducing programs deduce that this protein is a non-secretory protein.

  The mutein T11628_PEA_1_P10 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows SNPs as shown in Table 906) It is shown whether it is known and the presence of a known SNP in the mutein T11628_PEA_1_P10 sequence supports the putative sequence of this mutein of the invention).

  The mutein T11628_PEA_1_P10 is encoded by the following transcript: T11628_PEA_1_T4 (sequences shown at the end of the application). The code portion of the transcript T11628_PEA_1_T4 is shown in bold, starting from position 205 and ending at position 666. The transcript also has the following SNPs listed in Table 907 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein T11628_PEA_1_P10 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  As mentioned above, cluster T11628 is characterized by the 25 segments listed in Table 2 above, the sequence of which is shown at the end of the application. These segments are part of the nucleic acid sequence, which are of particular interest and are individually described herein. A description of each segment of the invention is provided herein.

  The segment cluster T11628_PEA_1_node_7 of the present invention is supported by nine libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T11628_PEA_1_T3. Table 908 below describes the start and end positions of this segment on each transcript.

  The segment cluster T11628_PEA_1_node_11 of the present invention is supported by one library. The number of libraries was determined as described above. This segment can be found in the following transcript: T11628_PEA_1_T5. Table 909 below describes the start and end positions of this segment on each transcript.

  The segment cluster T11628_PEA_1_node_16 of the present invention is supported by 38 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T11628_PEA_1_T11. Table 910 below describes the start and end positions of this segment on each transcript.

  The segment cluster T11628_PEA_1_node_22 of the present invention is supported by one library. The number of libraries was determined as described above. This segment can be found in the following transcript: T11628_PEA_1_T9. Table 911 below describes the start and end positions of this segment on each transcript.

  The segment cluster T11628_PEA_1_node_25 of the present invention is supported by 129 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: T11628_PEA_1_T3, T11628_PEA_1_T4, T11628_PEA_1_T5, T11628_PEA_1_T7, T11628_PEA_1_T9, and T11628_PEA_1_T11. Table 912 below describes the start and end positions of this segment on each transcript.

  Microarray (chip) data for this segment is also available, as follows. As described above, with respect to the clusters themselves, different oligonucleotides were tested for differential expression in different disease states, in particular cancer. The following oligonucleotides were found to reach this segment (for lung cancer) (shown in Table 913).

  The segment cluster T11628_PEA_1_node_31 of the present invention is supported by 137 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: T11628_PEA_1_T3, T11628_PEA_1_T4, T11628_PEA_1_T5, T11628_PEA_1_T7, T11628_PEA_1_T9, and T11628_PEA_1_T11. Table 914 below describes the start and end positions of this segment on each transcript.

  The segment cluster T11628_PEA_1_node_37 of the present invention is supported by 99 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: T11628_PEA_1_T3, T11628_PEA_1_T4, T11628_PEA_1_T5, T11628_PEA_1_T7, T11628_PEA_1_T9, and T11628_PEA_1_T11. Table 915 below describes the start and end positions of this segment on each transcript.

  According to an optional embodiment of the present invention, there is also provided a short segment associated with the above cluster. These segments are up to about 120 bp in length and are therefore included in the individual descriptions.

  The segment cluster T11628_PEA_1_node_0 of the present invention is supported by one library. The number of libraries was determined as described above. This segment can be found in the following transcript: T11628_PEA_1_T4. Table 916 below describes the start and end positions of this segment on each transcript.

  The segment cluster T11628_PEA_1_node_4 of the present invention is supported by two libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T11628_PEA_1_T4. Table 917 below describes the start and end positions of this segment on each transcript.

  The segment cluster T11628_PEA_1_node_9 of the present invention is supported by 16 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T11628_PEA_1_T5 and T11628_PEA_1_T7. Table 918 below describes the start and end positions of this segment on each transcript.

  The segment cluster T11628_PEA_1_node_13 according to the invention can be found in the following transcript: T11628_PEA_1_T7. Table 919 below describes the start and end positions of this segment on each transcript.

  The segment cluster T11628_PEA_1_node_14 of the present invention is supported by one library. The number of libraries was determined as described above. This segment can be found in the following transcript: T11628_PEA_1_T7. Table 920 below describes the start and end positions of this segment on each transcript.

  The segment cluster T11628_PEA_1_node_17 of the present invention is supported by 55 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: T11628_PEA_1_T11. Table 921 below describes the start and end positions of this segment on each transcript.

  The segment cluster T11628_PEA_1_node_18 of the present invention is supported by 98 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: T11628_PEA_1_T3, T11628_PEA_1_T4, T11628_PEA_1_T5, T11628_PEA_1_T7, and T11628_PEA_1_T11. Table 922 below describes the start and end positions of this segment on each transcript.

  The segment cluster T11628_PEA_1_node_19 according to the invention can be found in the following transcripts: T11628_PEA_1_T3, T11628_PEA_1_T4, T11628_PEA_1_T5, T11628_PEA_1_T7, and T11628_PEA_1_T11. Table 923 below describes the start and end positions of this segment on each transcript.

  The segment cluster T11628_PEA_1_node_24 of the present invention is supported by 112 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: T11628_PEA_1_T3, T11628_PEA_1_T4, T11628_PEA_1_T5, T11628_PEA_1_T7, T11628_PEA_1_T9, and T11628_PEA_1_T11. Table 924 below describes the start and end positions of this segment on each transcript.

Table 924-Position of segment on transcript

  The segment cluster T11628_PEA_1_node_27 of the present invention is supported by 119 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: T11628_PEA_1_T3, T11628_PEA_1_T4, T11628_PEA_1_T5, T11628_PEA_1_T7, T11628_PEA_1_T9, and T11628_PEA_1_T11. Table 925 below describes the start and end positions of this segment on each transcript.

  Microarray (chip) data for this segment is also available, as follows. As described above, with respect to the clusters themselves, different oligonucleotides were tested for differential expression in different disease states, in particular cancer. The following oligonucleotides were found to reach this segment (for lung cancer) (shown in Table 926).

  The segment cluster T11628_PEA_1_node_28 of the present invention is supported by 115 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: T11628_PEA_1_T3, T11628_PEA_1_T4, T11628_PEA_1_T5, T11628_PEA_1_T7, and T11628_PEA_1_T9. Table 927 below describes the start and end positions of this segment on each transcript.

  The segment cluster T11628_PEA_1_node_29 of the present invention is supported by 113 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: T11628_PEA_1_T3, T11628_PEA_1_T4, T11628_PEA_1_T5, T11628_PEA_1_T7, and T11628_PEA_1_T9. Table 928 below describes the start and end positions of this segment on each transcript.

  The segment cluster T11628_PEA_1_node_30 according to the invention can be found in the following transcripts: T11628_PEA_1_T3, T11628_PEA_1_T4, T11628_PEA_1_T5, T11628_PEA_1_T7, T11628_PEA_1_T9, and T11628_PEA_1_T11. Table 929 below describes the start and end positions of this segment on each transcript.

  The segment cluster T11628_PEA_1_node_32 according to the invention can be found in the following transcripts: T11628_PEA_1_T3, T11628_PEA_1_T4, T11628_PEA_1_T5, T11628_PEA_1_T7, T11628_PEA_1_T9, and T11628_PEA_1_T11. Table 930 below describes the start and end positions of this segment on each transcript.

  The segment cluster T11628_PEA_1_node_33 according to the invention can be found in the following transcripts: T11628_PEA_1_T3, T11628_PEA_1_T4, T11628_PEA_1_T5, T11628_PEA_1_T7, T11628_PEA_1_T9, and T11628_PEA_1_T11. Table 931 below describes the start and end positions of this segment on each transcript.

  The segment cluster T11628_PEA_1_node_34 of the present invention is supported by 122 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: T11628_PEA_1_T3, T11628_PEA_1_T4, T11628_PEA_1_T5, T11628_PEA_1_T7, T11628_PEA_1_T9, and T11628_PEA_1_T11. Table 932 below describes the start and end positions of this segment on each transcript.

  The segment cluster T11628_PEA_1_node_35 of the present invention is supported by 126 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: T11628_PEA_1_T3, T11628_PEA_1_T4, T11628_PEA_1_T5, T11628_PEA_1_T7, T11628_PEA_1_T9, and T11628_PEA_1_T11. Table 933 below describes the start and end positions of this segment on each transcript.

  The segment cluster T11628_PEA_1_node_36 of the present invention is supported by 122 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: T11628_PEA_1_T3, T11628_PEA_1_T4, T11628_PEA_1_T5, T11628_PEA_1_T7, T11628_PEA_1_T9, and T11628_PEA_1_T11. Table 934 below describes the start and end positions of this segment on each transcript.

Mutated protein alignment against previously known proteins:

Sequence name: Q8WVH6



Sequence documentation:



Alignment of: T11628_PEA_1_P2 x Q8WVH6 ..



Alignment segment 1/1:



Quality: 962.00 Escore: 0

Matching length: 99 Total length: 99

Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00

Total Percent Similarity: 100.00 Total Percent Identity: 100.00

Gaps: 0



Alignment:

....

56 MKASEDLKKHGATVLTALGGILKKKGHHEAEIKPLAQSHATKHKIPVKYL 105

||||||||||||||||||||||||||||||||||||||||

1 MKASEDLKKHGATVLTALGGILKKKGHHEAEIKPLAQHATKTHKIPVKYL 50

....

106 EFISECIIQVLQSKHPGDFGADAQGAMNKALELFRKDMASNYKELGFQG 154

||||||||||||||||||||||||||||||||||||||||

51 EFISECIIQVLQSKHPGDFGADAQGAMNKALELFRKDMASNYKELGFQG 99













Sequence name: MYG_HUMAN_V1



Sequence documentation:



Alignment of: T11628_PEA_1_P5 x MYG_HUMAN_V1 ..



Alignment segment 1/1:



Quality: 962.00 Escore: 0

Matching length: 99 Total length: 99

Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00

Total Percent Similarity: 100.00 Total Percent Identity: 100.00

Gaps: 0



Alignment:

....

1 MKASEDLKKHGATVLTALGGILKKKGHHEAEIKPLAQHATKTHKIPVKYL 50

||||||||||||||||||||||||||||||||||||||||

56 MKASEDLKKHGATVLTALGGILKKKGHHEAEIKPLAQSHATKHKIPVKYL 105

....

51 EFISECIIQVLQSKHPGDFGADAQGAMNKALELFRKDMASNYKELGFQG 99

||||||||||||||||||||||||||||||||||||||||

106 EFISECIIQVLQSKHPGDFGADAQGAMNKALELFRKDMASNYKELGFQG 154













Sequence name: MYG_HUMAN_V1



Sequence documentation:



Alignment of: T11628_PEA_1_P7 x MYG_HUMAN_V1 ..



Alignment segment 1/1:



Quality: 1315.00 Escore: 0

Matching length: 134 Total length: 134

Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00

Total Percent Similarity: 100.00 Total Percent Identity: 100.00

Gaps: 0



Alignment:

....

1 MGLSDGEWQLVLNVWGK VEADIPGHGQEVLIRLFKGHPETLEKDFK FKHL 50

||||||||||||||||||||||||||||||||||||||||

1 MGLSDGEWQLVLNVWGK VEADIPGHGQEVLIRLFKGHPETLEKDFK FKHL 50

....

51 KSEDEMKASEDLKKHGATVLTALGGILKKKGHHEAEIKPLAQSHATKHKI 100

||||||||||||||||||||||||||||||||||||||||

51 KSEDEMKASEDLKKHGATVLTALGGILKKKGHHEAEIKPLAQSHATKHKI 100

....

101 PVKYLEFISECIIQVLQSKHPGDFGADAQGAMNK 134

|||||||||||||||||||||||||||||||

101 PVKYLEFISECIIQVLQSKHPGDFGADAQGAMNK 134













Sequence name: Q8WVH6



Sequence documentation:



Alignment of: T11628_PEA_1_P10 x Q8WVH6 ..



Alignment segment 1/1:



Quality: 962.00 Escore: 0

Matching length: 99 Total length: 99

Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00

Total Percent Similarity: 100.00 Total Percent Identity: 100.00

Gaps: 0



Alignment:

....

56 MKASEDLKKHGATVLTALGGILKKKGHHEAEIKPLAQSHATKHKIPVKYL 105

||||||||||||||||||||||||||||||||||||||||

1 MKASEDLKKHGATVLTALGGILKKKGHHEAEIKPLAQHATKTHKIPVKYL 50

....

106 EFISECIIQVLQSKHPGDFGADAQGAMNKALELFRKDMASNYKELGFQG 154

||||||||||||||||||||||||||||||||||||||||

51 EFISECIIQVLQSKHPGDFGADAQGAMNKALELFRKDMASNYKELGFQG 99

Description of cluster HUMCEA The cluster HUMCEA is characterized by 5 transcripts and 42 segments of interest, the names of which are shown in Tables 935 and 936, respectively, and the sequences themselves are shown at the end of the application. Selected protein variants are shown in Table 937.

  These sequences are known proteins, previously known herein as proteins, oncofetal antigen-related cell adhesion molecule 5 precursor (SwissProt accession identifier CEA5_HUMAN, synonymous carcinoembryonic antigen, CEA, meconium Antigen 100, a variant of (also known as CD66e antigen) (SEQ ID NO: 1451).

  The sequence of the protein oncofetal antigen related cell adhesion molecule 5 precursor is shown at the end of the application as "oncofetal antigen related cell adhesion molecule 5 precursor amino acid sequence". Known polymorphisms of this sequence are shown in Table 938.

  Protein oncofetal antigen related cell adhesion molecule 5 precursor localization is thought to be membrane bound by the GPI-anchor.

  The previously known proteins also have the following indications and / or potential therapeutic applications: cancer. Clinical / therapeutic applications in humans (e.g. as targets for antibodies or small molecules and / or as direct therapy) are being investigated and available information related to these investigations is: Potential pharmaceutically relevant or therapeutically relevant activities of previously known proteins are: immunostimulants. The therapeutic role of proteins displayed by clusters is expected. Use or use this protein or part of it for potential treatment (contrast agent, anticancer drug, immune vehicle, immune complex, monoclonal antibody (mouse), antisense therapy, antibody) Clusters were assigned to this area as the information exists in drug databases or public databases (eg, above) that can.

  The following GO annotation applies to previously known proteins. The following annotations were found: endogenous plasma membrane proteins, membranes, which are annotations related to cellular components.

  GO assignments can be made at one or more http: // www. expasy. SwissProt / TremBl Protein knowledgebase available from ch / sprot / or http: // www. ncbi. nlm. nih. Depends on Locuslink available from gov / projects / LocusLink /.

  The cluster HUMCEA can be used as a diagnostic marker by overexpression of transcripts of this cluster in cancer. The expression of such transcripts in normal tissues is also shown by the method previously described. The terms “number” in the right column of the table and the numbers on the y-axis of FIG. 33 refer to the weighted expression of ESTs in each category as “ppm” (the ppm of ESTs of a particular cluster in this category by ppm) Ratio of expression to expression of all ESTs).

  In general, as shown for the histograms in FIG. 33 and Table 939, the following results were obtained. This cluster was overexpressed (at least at minimal levels) in the following pathological conditions: epithelial malignancies, a mixture of malignancies from different tissues, and pancreatic cancer.

  For this cluster, at least one oligonucleotide was found to demonstrate overexpression of the cluster, but not in at least one transcript / segment listed below. Microarray (chip) data for this segment is also available, as follows. As noted above, different oligonucleotides were tested for differential expression in different disease states, in particular cancer. The following oligonucleotides were found to reach this cluster (for lung cancer) but not the other segments / transcripts below (shown in Table 941).

  As mentioned above, cluster HUMCEA is characterized by the 5 transcripts listed in Table 1 above. These transcripts encode a protein which is a variant of the protein oncofetal antigen related cell adhesion molecule 5 precursor. A description of each mutein of the invention is provided herein.

  The mutein HUMCEA_PEA_1_P4 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript HUMCEA_PEA_1_T8. An alignment to a known protein (carcinoembryonic antigen-related cell adhesion molecule 5 precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Reporting of comparison between HUMCEA_PEA_1_P4 and CEA5_HUMAN 1. Corresponding to amino acids 1-234 of CEA5_HUMAN, first amino acid sequence at least 90% homologous to the corresponding MESPSAPPHRWCIPWQRLLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLVHNLPQHLFGYSWYKGERVDGNRQIIGYVIGTQQATPGPAYSGREIIYPNASLLIQNIIQNDTGFYTLHVIKSDLVNEEATGQFRVYPELPKPSISSNNSKPVEDKDAVAFTCEPETQDATYLWWVNNQSLPVSPRLQLSNGNRTLTLFNVTRNDTASYKCETQNPVSARRSDSVILNVL to amino acids 1-234 of HUMCEA_PEA_1_P4, the HUMCEA_PEA_1_P4 amino The polypeptide having the sequence CEYICSSLAQAASPNPQGQRQDFSVPLRFKYTDPQPTSRLSVTFCPRKTADQVLTKRRGGAASVLGGGSTPYDGRNR corresponding to 35-315 is at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous to the second amino acid An isolated chimeric polypeptide encoding HUMCEA_PEA_1_P4, comprising a sequence, wherein said first and second amino acid sequences are adjacent and in sequential order.

  2. A sequence of at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95%. An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein HUMCEA_PEA_1_P4 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows SNPs as shown in Table 942) It indicates whether it is known and the presence of a known SNP in the mutant protein HUMCEA_PEA_1_P4 sequence supports the deduced sequence of this mutant protein according to the invention).

  The glycosylation sites of the mutant protein HUMCEA_PEA_1_P4 compared to the known protein oncofetal antigen related cell adhesion molecule 5 precursor are shown in Table 943 (the first column shows its position on the amino acid sequence, the second column is , Indicates whether glycosylation sites are present in the mutein, and the last column indicates whether this position differs on the mutein).

  The mutein HUMCEA_PEA_1_P4 is encoded by the following transcript: HUMCEA_PEA_1_T8 (sequences shown at the end of the application). The coding part of the transcript HUMCEA_PEA_1_T8 is shown in bold, starting from position 115 and ending at position 1059. The transcript also has the following SNPs listed in Table 944 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, the mutein HUMCEA_PEA_1_P4 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein HUMCEA_PEA_1_P5 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript HUMCEA_PEA_1_T9. An alignment to a known protein (carcinoembryonic antigen-related cell adhesion molecule 5 precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Reporting of the comparison between HUMCEA_PEA_1_P5 and CEA5_HUMAN 1. Corresponding to amino acids 1 to 675 of CEA5_HUMAN, corresponding to amino acids 1 to 675 of HUMCEA_PEA_1_P5 MESPSAPPHRWCIPWQRLLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLVHNLPQHLFGYSWYKGERVDGNRQIIGYVIGTQQATPGPAYSGREIIYPNASLLIQNIIQNDTGFYTLHVIKSDLVNEEATGQFRVYPELPKPSISSNNSKPVEDKDAVAFTCEPETQDATYLWWVNNQSLPVSPRLQLSNGNRTLTLFNVTRNDTASYKCETQNPVSARRSDSVILNVLYGPDAPTISPLNTSYRSGENLNLSCHAASNPPAQYSWFVNGTF QSTQELFIPNITVNNSGSYTCQAHNSDTGLNRTTVTTITVYAEPPKPFITSNNSNPVEDEDAVALTCEPEIQNTTYLWWVNNQSLPVSPRLQLSNDNRTLTLLSVTRNDVGPYECGIQNELSVDHSDPVILNVLYGPDDPTISPSYTYYRPGVNLSLSCHAASNPPAQYSWLIDGNIQQHTQELFISNITEKNSGLYTCQANNSASGHSRTTVKTITVSAELPKPSISSNNSKPVEDKDAVAFTCEPEAQNTTYLWWVNGQSLPVSPRLQLSNGNRTLTLFNVTRNDARAYVCGIQNSVSANRSDPVTLDVLYGPDTPIISPPDSSYLSGAN NLCHSASNPSPQYSWRINGIPQQHTQVLFIAKITPNNGGTYACFVSNLATGRNNSIVKSITVS A first amino acid sequence at least 90% homologous to the first amino acid and a sequence GKWLPGACASYSGVESIWFSPKSQEDIFPSLCSMGGTQSQILS corresponding to amino acids 676 to 719 of HUMCEA_PEA_1_P5 Comprises HUMCEA_PEA_1_P5, comprising a second amino acid sequence which is at least 90%, most preferably at least 95% homologous, said first and second amino acid sequences being adjacent and in sequential order Isolated chimera polypep Tide.

  2. HUMCEA_PEA_1_P5 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence GKWLPGASASYSGVESIWFSPKSQEDIFFPSLCSMGTRKSQILS in HUMCEA_PEA_1_P5 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein HUMCEA_PEA_1_P5 also has the following non-silent SNPs (single nucleotide polymorphisms) (indicating its position on the amino acid sequence, listing other amino acids, and the last column, as shown in Table 945) It is indicated whether it is known and the presence of a known SNP in the mutant protein HUMCEA_PEA_1_P5 sequence supports the deduced sequence of this mutant protein according to the invention).

  The glycosylation sites of the mutant protein HUMCEA_PEA_1_P5 compared to the known protein oncofetal antigen related cell adhesion molecule 5 precursor are shown in Table 946 (in the first column, its position on the amino acid sequence is indicated, the second column is , Indicates whether glycosylation sites are present in the mutein, and the last column indicates whether this position differs on the mutein).

  The mutein HUMCEA_PEA_1_P5 is encoded by the following transcript: HUMCEA_PEA_1_T9 (sequences shown at the end of the application). The coding part of the transcript HUMCEA_PEA_1_T9 is shown in bold, starting from position 115 and ending at position 2721. The transcript also has the following SNPs listed in Table 947 (indicating its position on the nucleotide sequence and listing another nucleic acid, the last column indicates whether the SNP is known, the mutein HUMCEA_PEA_1_P5 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein HUMCEA_PEA_1_P14 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript HUMCEA_PEA_1_T20. The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein HUMCEA_PEA_1_P14 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows SNPs as shown in Table 948) It indicates whether it is known and the presence of a known SNP in the mutant protein HUMCEA_PEA_1_P14 sequence supports the deduced sequence of this mutant protein according to the invention).

  The mutein HUMCEA_PEA_1_P14 is encoded by the following transcript: HUMCEA_PEA_1_T20 (sequences shown at the end of the application). The coding part of the transcript HUMCEA_PEA_1_T20 is shown in bold, starting from position 115 and ending at position 1821. The transcript also has the following SNPs listed in Table 949 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, the mutein HUMCEA_PEA_1_P14 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein HUMCEA_PEA_1_P19 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript HUMCEA_PEA_1_T25. An alignment to a known protein (carcinoembryonic antigen-related cell adhesion molecule 5 precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Reporting of the comparison between HUMCEA_PEA_1_P19 and CEA5_HUMAN 1. Corresponding to amino acids 1-232 of CEA5_HUMAN, corresponding MESPSAPPHRWCIPWQRLLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLVHNLPQHLFGYSWYKGERVDGNRQIIGYVIGTQQATPGPAYSGREIIYPNASLLIQNIIQNDTGFYTLHVIKSDLVNEEATGQFRVYPELPKPSISSNNSKPVEDKDAVAFTCEPETQDATYLWWVNNQSLPVSPRLQLSNGNRTLTLFNVTRNDTASYKCETQNPVSARRSDSVILN and at least 90% homologous to the first amino acid sequence to amino acids 1-232 of HUMCEA_PEA_1_P19, amino acids CEA5_HUMAN 589 to 70 Corresponding to the amino acids 233 to 346 of HUMCEA_PEA_1_P19 corresponding to the amino acid sequence of at least 90% of the amino acid sequence of An isolated chimeric polypeptide encoding HUMCEA_PEA_1_P19, in order.

  2. Length “n” (wherein n is at least about 10 amino acids long, optionally at least about 20 amino acids long, preferably at least about 30 amino acids long, more preferably at least about 40 amino acids long, most preferably at least about 50 amino acids long, at least two amino acids comprising NV, starting from any of the following structures: amino acid numbers 232-x to 232, amino acid numbers 233 + ((n-2)-x) (formula An isolated chimeric polypeptide encoding the edge portion of HUMCEA_PEA_1_P19, comprising a polypeptide, having a sequence terminating in:

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: membrane. Protein localization is considered to be membrane by manual investigation of known protein localization and / or gene structure.

  The mutein HUMCEA_PEA_1_P19 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column, as shown in Table 950) It indicates whether it is known and the presence of a known SNP in the mutant protein HUMCEA_PEA_1_P19 sequence supports the deduced sequence of this mutant protein according to the invention).

  The glycosylation sites of the mutant protein HUMCEA_PEA_1_P19 as compared to the known protein oncofetal antigen related cell adhesion molecule 5 precursor are shown in Table 951 (the first column shows its position on the amino acid sequence, the second column is , Indicates whether glycosylation sites are present in the mutein, and the last column indicates whether this position differs on the mutein).

  The mutein HUMCEA_PEA_1_P19 is encoded by the following transcript: HUMCEA_PEA_1_T25 (sequences shown at the end of the application). The coding part of the transcript HUMCEA_PEA_1_T25 is shown in bold, starting from position 115 and ending at position 1152. The transcript also has the following SNPs listed in Table 952 (showing its position on the nucleotide sequence and listing another nucleic acid, the last column indicating whether the SNP is known, the mutein HUMCEA_PEA_1_P19 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein HUMCEA_PEA_1_P20 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript HUMCEA_PEA_1_T26. An alignment to a known protein (carcinoembryonic antigen-related cell adhesion molecule 5 precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Reporting of comparison between HUMCEA_PEA_1_P20 and CEA5_HUMAN 1. Corresponding to amino acids 1-142 of CEA5_HUMAN, first amino acid sequence at least 90% homologous to the corresponding MESPSAPPHRWCIPWQRLLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLVHNLPQHLFGYSWYKGERVDGNRQIIGYVIGTQQATPGPAYSGREIIYPNASLLIQNIIQNDTGFYTLHVIKSDLVNEEATGQFRVYP to amino acids 1-142 of HUMCEA_PEA_1_P20, corresponding to amino acids 499-702 of CEA5_HUMAN, the HUMCEA_PEA_1_P20 amino 143-346 Also corresponding to ELPKPSISSNNSKPVEDKDAFAFTCEPEAQNTT YRWWNGNGSLPSPVSLQ SNGNRTLTLFNVTRNDARAYVCGIQNSVSANRSDPVTLDVLYGPDTPIISPPDSSYLSGANLNLSCHSASNPSPQYSWRINGIPQQHTQVLFIAKITPNNNGTYACFVSNLATGRNNSIVKSITVSASGTSPGLSAGATVGIMIGVLVGVALI and and at least 90% homologous to a second amino acid sequence, the first amino acid sequence and a second amino acid sequence, contiguous and in sequential order, the isolated chimeric polypeptide coding HUMCEA_PEA_1_P20.

  2. Length “n” (wherein n is at least about 10 amino acids long, optionally at least about 20 amino acids long, preferably at least about 30 amino acids long, more preferably at least about 40 amino acids long, most preferably at least about 50 amino acids long, at least two amino acids comprising PE, starting from any of the following structures: amino acids 142-x to 142, amino acids 143 + ((n-2) -x) (formula An isolated chimeric polypeptide encoding the edge portion of HUMCEA_PEA_1_P20, comprising a polypeptide, having a sequence terminating in:), wherein x is varied from 0 to n-2.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: membrane. Protein localization is considered to be membrane by manual investigation of known protein localization and / or gene structure.

  The mutein HUMCEA_PEA_1_P20 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows the SNPs, as shown in Table 953) It is shown whether it is known and the presence of a known SNP in the mutant protein HUMCEA_PEA_1_P20 sequence supports the deduced sequence of this mutant protein according to the invention).

  The glycosylation sites of the mutant protein HUMCEA_PEA_1_P20 as compared to the known protein oncofetal antigen related cell adhesion molecule 5 precursor are shown in Table 954 (showing its position on the amino acid sequence in the first column, the second column , Indicates whether glycosylation sites are present in the mutein, and the last column indicates whether this position differs on the mutein).

  The mutein HUMCEA_PEA_1_P20 is encoded by the following transcript: HUMCEA_PEA_1_T26 (sequences shown at the end of the application). The coding part of the transcript HUMCEA_PEA_1_T26 is shown in bold, starting from position 115 and ending at position 1152. The transcript also has the following SNPs listed in Table 955 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, the mutein HUMCEA_PEA_1_P20 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  As noted above, cluster HUMCEA is characterized by the 42 segments listed in Table 2 above, the sequences of which are shown at the end of the application. These segments are part of the nucleic acid sequence, which are of particular interest and are individually described herein. A description of each segment of the invention is provided herein.

  The segment cluster HUMCEA_PEA_1_node_0 of the present invention is supported by 56 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMCEA_PEA_1_T8, HUMCEA_PEA_1_T9, HUMCEA_PEA_1_T20, HUMCEA_PEA_1_T25, and HUMCEA_PEA_1_T26. Table 956 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCEA_PEA_1_node_2 of the present invention is supported by 83 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMCEA_PEA_1_T8, HUMCEA_PEA_1_T9, HUMCEA_PEA_1_T20, HUMCEA_PEA_1_T25, and HUMCEA_PEA_1_T26. Table 957 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCEA_PEA_1_node_11 of the present invention is supported by six libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMCEA_PEA_1_T8. Table 958 below describes the start and end positions of this segment on each transcript.

  Microarray (chip) data for this segment is also available, as follows. As described above, with respect to the clusters themselves, different oligonucleotides were tested for differential expression in different disease states, in particular cancer. The following oligonucleotides were found to reach this segment (for lung cancer) (shown in Table 959).

  The segment cluster HUMCEA_PEA_1_node_12 of the present invention is supported by 83 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMCEA_PEA_1_T8, HUMCEA_PEA_1_T9 and HUMCEA_PEA_1_T20. Table 960 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCEA_PEA_1_node_31 of the present invention is supported by 87 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMCEA_PEA_1_T8, HUMCEA_PEA_1_T9, and HUMCEA_PEA_1_T20. Table 961 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCEA_PEA_1_node_36 of the present invention is supported by 94 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMCEA_PEA_1_T8, HUMCEA_PEA_1_T9, and HUMCEA_PEA_1_T26. Table 962 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCEA_PEA_1_node_44 of the present invention is supported by 112 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMCEA_PEA_1_T8, HUMCEA_PEA_1_T9, HUMCEA_PEA_1_T25, and HUMCEA_PEA_1_T26. Table 963 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCEA_PEA_1_node_46 of the present invention is supported by 15 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMCEA_PEA_1_T9. Table 964 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCEA_PEA_1_node_63 of the present invention is supported by 68 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMCEA_PEA_1_T8, HUMCEA_PEA_1_T25, and HUMCEA_PEA_1_T26. Table 965 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCEA_PEA_1_node_65 of the present invention is supported by 54 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMCEA_PEA_1_T8, HUMCEA_PEA_1_T25, and HUMCEA_PEA_1_T26. Table 966 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCEA_PEA_1_node_67 of the present invention is supported by two libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMCEA_PEA_1_T20. Table 967 below describes the start and end positions of this segment on each transcript.

  According to an optional embodiment of the present invention, there is also provided a short segment associated with the above cluster. These segments are up to about 120 bp in length and are therefore included in the individual descriptions.

  The segment cluster HUMCEA_PEA_1_node_3 of the present invention is supported by 67 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMCEA_PEA_1_T8, HUMCEA_PEA_1_T9, HUMCEA_PEA_1_T20, HUMCEA_PEA_1_T25, and HUMCEA_PEA_1_T26. Table 968 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCEA_PEA_1_node_7 of the present invention is supported by 73 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMCEA_PEA_1_T8, HUMCEA_PEA_1_T9, HUMCEA_PEA_1_T20, and HUMCEA_PEA_1_T25. Table 969 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCEA_PEA_1_node_8 of the present invention is supported by 67 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMCEA_PEA_1_T8, HUMCEA_PEA_1_T9, HUMCEA_PEA_1_T20, and HUMCEA_PEA_1_T25. Table 970 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCEA_PEA_1_node_9 of the present invention is supported by 71 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMCEA_PEA_1_T8, HUMCEA_PEA_1_T9, HUMCEA_PEA_1_T20, and HUMCEA_PEA_1_T25. Table 971 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCEA_PEA_1_node_10 of the present invention is supported by 67 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMCEA_PEA_1_T8, HUMCEA_PEA_1_T9, HUMCEA_PEA_1_T20, and HUMCEA_PEA_1_T25. Table 972 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCEA_PEA_1_node_15 of the invention can be found in the following transcripts: HUMCEA_PEA_1_T8, HUMCEA_PEA_1_T9, and HUMCEA_PEA_1_T20. Table 973 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCEA_PEA_1_node_16 according to the invention can be found in the following transcripts: HUMCEA_PEA_1_T8, HUMCEA_PEA_1_T9, and HUMCEA_PEA_1_T20. Table 974 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCEA_PEA_1_node_17 according to the invention can be found in the following transcripts: HUMCEA_PEA_1_T8, HUMCEA_PEA_1_T9, and HUMCEA_PEA_1_T20. Table 975 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCEA_PEA_1_node_18 according to the invention can be found in the following transcript: HUMCEA_PEA_1_T8, HUMCEA_PEA_1_T9, and HUMCEA_PEA_1_T20. Table 976 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCEA_PEA_1_node_19 of the present invention is supported by 69 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMCEA_PEA_1_T8, HUMCEA_PEA_1_T9, and HUMCEA_PEA_1_T20. Table 977 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCEA_PEA_1_node_20 according to the invention can be found in the following transcripts: HUMCEA_PEA_1_T8, HUMCEA_PEA_1_T9, and HUMCEA_PEA_1_T20. Table 978 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCEA_PEA_1_node_21 according to the invention can be found in the following transcript: HUMCEA_PEA_1_T8, HUMCEA_PEA_1_T9, and HUMCEA_PEA_1_T20. Table 979 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCEA_PEA_1_node_22 of the present invention is supported by 77 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMCEA_PEA_1_T8, HUMCEA_PEA_1_T9, and HUMCEA_PEA_1_T20. Table 980 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCEA_PEA_1_node_23 of the present invention is supported by 72 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMCEA_PEA_1_T8, HUMCEA_PEA_1_T9, and HUMCEA_PEA_1_T20. Table 981 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCEA_PEA_1_node_24 according to the invention can be found in the following transcripts: HUMCEA_PEA_1_T8, HUMCEA_PEA_1_T9, and HUMCEA_PEA_1_T20. Table 982 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCEA_PEA_1_node_27 according to the invention can be found in the following transcripts: HUMCEA_PEA_1_T8, HUMCEA_PEA_1_T9, and HUMCEA_PEA_1_T20. Table 983 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCEA_PEA_1_node_29 according to the invention can be found in the following transcripts: HUMCEA_PEA_1_T8, HUMCEA_PEA_1_T9, and HUMCEA_PEA_1_T20. Table 984 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCEA_PEA_1_node_30 of the present invention is supported by 67 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMCEA_PEA_1_T8, HUMCEA_PEA_1_T9, and HUMCEA_PEA_1_T20. Table 985 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCEA_PEA_1_node_33 of the invention can be found in the following transcripts: HUMCEA_PEA_1_T8, HUMCEA_PEA_1_T9, and HUMCEA_PEA_1_T26. Table 986 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCEA_PEA_1_node_34 of the present invention is supported by 80 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMCEA_PEA_1_T8, HUMCEA_PEA_1_T9, and HUMCEA_PEA_1_T26. Table 987 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCEA_PEA_1_node_35 of the present invention is supported by 75 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMCEA_PEA_1_T8, HUMCEA_PEA_1_T9, and HUMCEA_PEA_1_T26. Table 988 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCEA_PEA_1_node_45 of the present invention is supported by nine libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMCEA_PEA_1_T9. Table 998 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCEA_PEA_1_node_50 of the present invention is supported by 64 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMCEA_PEA_1_T8, HUMCEA_PEA_1_T25, and HUMCEA_PEA_1_T26. Table 990 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCEA_PEA_1_node_51 of the present invention is supported by 88 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMCEA_PEA_1_T8, HUMCEA_PEA_1_T25, and HUMCEA_PEA_1_T26. Table 991 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCEA_PEA_1_node_56 of the present invention is supported by 75 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMCEA_PEA_1_T8, HUMCEA_PEA_1_T25, and HUMCEA_PEA_1_T26. Table 992 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCEA_PEA_1_node_57 of the present invention is supported by 82 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMCEA_PEA_1_T8, HUMCEA_PEA_1_T25, and HUMCEA_PEA_1_T26. Table 993 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCEA_PEA_1_node_58 of the present invention is supported by 63 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMCEA_PEA_1_T8, HUMCEA_PEA_1_T25, and HUMCEA_PEA_1_T26. Table 994 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCEA_PEA_1_node_60 of the present invention is supported by 55 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMCEA_PEA_1_T8, HUMCEA_PEA_1_T25, and HUMCEA_PEA_1_T26. Table 995 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCEA_PEA_1_node_61 according to the invention can be found in the following transcripts: HUMCEA_PEA_1_T8, HUMCEA_PEA_1_T25, and HUMCEA_PEA_1_T26. Table 996 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCEA_PEA_1_node_62 of the present invention is supported by 60 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMCEA_PEA_1_T8, HUMCEA_PEA_1_T25, and HUMCEA_PEA_1_T26. Table 997 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMCEA_PEA_1_node_64 of the present invention is supported by 45 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMCEA_PEA_1_T8, HUMCEA_PEA_1_T25, and HUMCEA_PEA_1_T26. Table 998 below describes the start and end positions of this segment on each transcript.

Mutated protein alignment against previously known proteins:
Sequence name: CEA5_HUMAN

Sequence documentation:

Alignment of: HUMCEA_PEA_1_P4 x CEA5_HUMAN ..

Alignment segment 1/1:

Quality: 2320.00 Escore: 0
Matching length: 234 Total length: 234
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MESPSAPPHRWCIPWQRLLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50
||||||||||||||||||||||||||||||||||||||||
1 MESPSAPPHRWCIPWQRLLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50
....
51 VLLLVHNLPQHLFGYSWYKGERVDGNRQIIGYVIGTQQATPGPAYSGREI 100
||||||||||||||||||||||||||||||||||||||||
51 VLLLVHNLPQHLFGYSWYKGERVDGNRQIIGYVIGTQQATPGPAYSGREI 100
....
101 IYPNASLLIQNIIQNDTGFYTLHVIKSDLVNEEATGQFRVYPELPKPSIS 150
||||||||||||||||||||||||||||||||||||||||
101 IYPNASLLIQNIIQNDTGFYTLHVIKSDLVNEEATGQFRVYPELPKPSIS 150
....
151 SNNSPVPEDKDAVAFTCEPETQDATYLWWVNNQSLPSPRSLLSGNGNRTL 200
||||||||||||||||||||||||||||||||||||||||
151 SNNSPVPEDKDAVAFTCEPETQDATYLWWVNNQSLPSPRSLLSGNGNRTL 200
....
201 TLFNFTRNDTASYKCETQ NPVSARRSDSVILNVL 234
|||||||||||||||||||||||||||||||
201 TLFNFTRNDTASYKCETQ NPVSARRSDSVILNVL 234






Sequence name: CEA5_HUMAN

Sequence documentation:

Alignment of: HUMCEA_PEA_1_P5 x CEA5_HUMAN ..

Alignment segment 1/1:

Quality: 6692.00 Escore: 0
Matching length: 675 Total length: 675
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MESPSAPPHRWCIPWQRLLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50
||||||||||||||||||||||||||||||||||||||||
1 MESPSAPPHRWCIPWQRLLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50
....
51 VLLLVHNLPQHLFGYSWYKGERVDGNRQIIGYVIGTQQATPGPAYSGREI 100
||||||||||||||||||||||||||||||||||||||||
51 VLLLVHNLPQHLFGYSWYKGERVDGNRQIIGYVIGTQQATPGPAYSGREI 100
....
101 IYPNASLLIQNIIQNDTGFYTLHVIKSDLVNEEATGQFRVYPELPKPSIS 150
||||||||||||||||||||||||||||||||||||||||
101 IYPNASLLIQNIIQNDTGFYTLHVIKSDLVNEEATGQFRVYPELPKPSIS 150
....
151 SNNSPVPEDKDAVAFTCEPETQDATYLWWVNNQSLPSPRSLLSGNGNRTL 200
||||||||||||||||||||||||||||||||||||||||
151 SNNSPVPEDKDAVAFTCEPETQDATYLWWVNNQSLPSPRSLLSGNGNRTL 200
....
201 TLFNFTRNDTASYKCETQ NPVSARRSDSVILNVLYGPDAPTISPLNTSYR 250
||||||||||||||||||||||||||||||||||||||||
201 TLFNFTRNDTASYKCETQ NPVSARRSDSVILNVLYGPDAPTISPLNTSYR 250
....
251 SGENLNLSCHAASNPPAQ YSWF VNGTFQQSTQELFIPNITVNNSGSYTCQ 300
||||||||||||||||||||||||||||||||||||||||
251 SGENLNLSCHAASNPPAQ YSWF VNGTFQQSTQELFIPNITVNNSGSYTCQ 300
....
301 AHNSDTGLNRTTVTTTVYAEPPKPFITSNNSNPVEDEDAVALTCEPEIQ 350
||||||||||||||||||||||||||||||||||||||||
301 AHNSDTGLNRTTVTTTVYAEPPKPFITSNNSNPVEDEDAVALTCEPEIQ 350
....
351 NTTYLWWVNNQSLPVSPRLQLSNLDRTLLSVTRNDVGPYECGIQNELS 400
||||||||||||||||||||||||||||||||||||||||
351 NTTYLWWVNNQSLPVSPRLQLSNLDRTLLSVTRNDVGPYECGIQNELS 400
....
401 VDHSDPVILNVLYGPDDPTISPSYTYYRPGNLSLSCHAASNPPAQYSWL 450
||||||||||||||||||||||||||||||||||||||||
401 VDHSDPVILNVLYGPDDPTISPSYTYYRPGNLSLSCHAASNPPAQYSWL 450
....
451 IDGNIQQHTQELFISNITEKNSGLYTCQANNSASGHSRTTVKTITVSAEL 500
||||||||||||||||||||||||||||||||||||||||
451 IDGNIQQHTQELFISNITEKNSGLYTCQANNSASGHSRTTVKTITVSAEL 500
....
501 PKPSISSNNSKPVEDKDAFAFTCEPEAQNTTYLWWVNGQSLPVSPRLQLS 550
||||||||||||||||||||||||||||||||||||||||
501 PKPSISSNNSKPVEDKDAFAFTCEPEAQNTTYLWWVNGQSLPVSPRLQLS 550
....
551 NGNRTLTLFNVTRNDARAYVCGIQNSVSANRSDPVTLDVLYGPDTPIISP 600
||||||||||||||||||||||||||||||||||||||||
551 NGNRTLTLFNVTRNDARAYVCGIQNSVSANRSDPVTLDVLYGPDTPIISP 600
....
601 PDSSYLSGANLNLSCHSASNPSPQYSWRINGIPQQHTQVLFIAKITPNN 650
||||||||||||||||||||||||||||||||||||||||
601 PDSSYLSGANLNLSCHSASNPSPQYSWRINGIPQQHTQVLFIAKITPNN 650
.
651 GTYACFVSNLATGRNNSIVKSITVS 675
||||||||||||||||||||||||
651 GTYACFVSNLATGRNNSIVKSITVS 675






Sequence name: CEA5_HUMAN

Sequence documentation:

Alignment of: HUMCEA_PEA_1_P19 x CEA5_HUMAN ..

Alignment segment 1/1:

Quality: 3298.00 Escore: 0
Matching length: 346 Total length: 702
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 49.29 Total Percent Identity: 49.29
Gaps: 1

Alignment:
....
1 MESPSAPPHRWCIPWQRLLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50
||||||||||||||||||||||||||||||||||||||||
1 MESPSAPPHRWCIPWQRLLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50
....
51 VLLLVHNLPQHLFGYSWYKGERVDGNRQIIGYVIGTQQATPGPAYSGREI 100
||||||||||||||||||||||||||||||||||||||||
51 VLLLVHNLPQHLFGYSWYKGERVDGNRQIIGYVIGTQQATPGPAYSGREI 100
....
101 IYPNASLLIQNIIQNDTGFYTLHVIKSDLVNEEATGQFRVYPELPKPSIS 150
||||||||||||||||||||||||||||||||||||||||
101 IYPNASLLIQNIIQNDTGFYTLHVIKSDLVNEEATGQFRVYPELPKPSIS 150
....
151 SNNSPVPEDKDAVAFTCEPETQDATYLWWVNNQSLPSPRSLLSGNGNRTL 200
||||||||||||||||||||||||||||||||||||||||
151 SNNSPVPEDKDAVAFTCEPETQDATYLWWVNNQSLPSPRSLLSGNGNRTL 200
....
201 TLFNDVRNDTASYKCETQNPVSARRSDSVILN .................. 232
||||||||||||||||||||||||||||||
201 TLFNFTRNDTASYKCETQ NPVSARRSDSVILNVLYGPDAPTISPLNTSYR 250
....
232 ...................................................... . 232

251 SGENLNLSCHAASNPPAQ YSWF VNGTFQQSTQELFIPNITVNNSGSYTCQ 300
....
232 ...................................................... . 232

301 AHNSDTGLNRTTVTTTVYAEPPKPFITSNNSNPVEDEDAVALTCEPEIQ 350
....
232 ...................................................... . 232

351 NTTYLWWVNNQSLPVSPRLQLSNLDRTLLSVTRNDVGPYECGIQNELS 400
....
232 ...................................................... . 232

401 VDHSDPVILNVLYGPDDPTISPSYTYYRPGNLSLSCHAASNPPAQYSWL 450
....
232 ...................................................... . 232

451 IDGNIQQHTQELFISNITEKNSGLYTCQANNSASGHSRTTVKTITVSAEL 500
....
232 ...................................................... . 232

501 PKPSISSNNSKPVEDKDAFAFTCEPEAQNTTYLWWVNGQSLPVSPRLQLS 550
....
233 ......................................... VLYGPDTPIISP 244
||||||||||||
551 NGNRTLTLFNVTRNDARAYVCGIQNSVSANRSDPVTLDVLYGPDTPIISP 600
....
245 PDSSYLSGANLNLSCHSASNSPSPQYSWRINGIPQQHTQVLFIAKITPNN 294
||||||||||||||||||||||||||||||||||||||||
601 PDSSYLSGANLNLSCHSASNPSPQYSWRINGIPQQHTQVLFIAKITPNN 650
....
295 GTYACFVSRNLATGRNNSIVKSITVSASGTSPGLSAGATVGIMIGVLVGVA 344
||||||||||||||||||||||||||||||||||||||||
651 GTYACFVSRNLATGRNNSIVKSITVSASGTSPGLSAGATVGIMIGVLVGVA 700

345 LI 346
||
701 LI 702






Sequence name: CEA5_HUMAN

Sequence documentation:

Alignment of: HUMCEA_PEA_1_P20 x CEA5_HUMAN ..

Alignment segment 1/1:

Quality: 3294.00 Escore: 0
Matching length: 346 Total length: 702
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 49.29 Total Percent Identity: 49.29
Gaps: 1

Alignment:
....
1 MESPSAPPHRWCIPWQRLLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50
||||||||||||||||||||||||||||||||||||||||
1 MESPSAPPHRWCIPWQRLLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50
....
51 VLLLVHNLPQHLFGYSWYKGERVDGNRQIIGYVIGTQQATPGPAYSGREI 100
||||||||||||||||||||||||||||||||||||||||
51 VLLLVHNLPQHLFGYSWYKGERVDGNRQIIGYVIGTQQATPGPAYSGREI 100
....
101 IYPNASLLIQNIIQNDTGFYTLHVIKSDLVNEEATGQFRVYP ..... 142
|||||||||||||||||||||||||||||||||||||
101 IYPNASLLIQNIIQNDTGFYTLHVIKSDLVNEEATGQFRVYPELPKPSIS 150
....
142 ...................................................... . 142

151 SNNSPVPEDKDAVAFTCEPETQDATYLWWVNNQSLPSPRSLLSGNGNRTL 200
....
142 ...................................................... . 142

201 TLFNFTRNDTASYKCETQ NPVSARRSDSVILNVLYGPDAPTISPLNTSYR 250
....
142 ...................................................... . 142

251 SGENLNLSCHAASNPPAQ YSWF VNGTFQQSTQELFIPNITVNNSGSYTCQ 300
....
142 ...................................................... . 142

301 AHNSDTGLNRTTVTTTVYAEPPKPFITSNNSNPVEDEDAVALTCEPEIQ 350
....
142 ...................................................... . 142

351 NTTYLWWVNNQSLPVSPRLQLSNLDRTLLSVTRNDVGPYECGIQNELS 400
....
142 ...................................................... . 142

401 VDHSDPVILNVLYGPDDPTISPSYTYYRPGNLSLSCHAASNPPAQYSWL 450
....
143 ................................................... EL 144
||
451 IDGNIQQHTQELFISNITEKNSGLYTCQANNSASGHSRTTVKTITVSAEL 500
....
145 PKPSISSNNSKPVEDKDAFAFTCEPEAQNTTYLWWVNGQSLPVSPRLQLS 194
||||||||||||||||||||||||||||||||||||||||
501 PKPSISSNNSKPVEDKDAFAFTCEPEAQNTTYLWWVNGQSLPVSPRLQLS 550
....
195 NGNRTLTLFNVTRNDARAYVCGIQNSVSANRSDPVTLDVLYGPDTPIISP 244
||||||||||||||||||||||||||||||||||||||||
551 NGNRTLTLFNVTRNDARAYVCGIQNSVSANRSDPVTLDVLYGPDTPIISP 600
....
245 PDSSYLSGANLNLSCHSASNSPSPQYSWRINGIPQQHTQVLFIAKITPNN 294
||||||||||||||||||||||||||||||||||||||||
601 PDSSYLSGANLNLSCHSASNPSPQYSWRINGIPQQHTQVLFIAKITPNN 650
....
295 GTYACFVSRNLATGRNNSIVKSITVSASGTSPGLSAGATVGIMIGVLVGVA 344
||||||||||||||||||||||||||||||||||||||||
651 GTYACFVSRNLATGRNNSIVKSITVSASGTSPGLSAGATVGIMIGVLVGVA 700

345 LI 346
||
701 LI 702

Description of Cluster R35137 Cluster R35137 features 6 transcripts of interest and 20 segments, the names of which are shown in Tables 999 and 1000, respectively, and the sequence itself is shown at the end of the application. Selected protein variants are shown in Table 1001.

  These sequences are known proteins alanine aminotransferase (SwissProt accession identifier ALAT_HUMAN, synonym EC 2.6.1.2, glutamate-pyruvate transaminase, GPT, previously known herein as a protein) , A variant of glutamic acid-alanine transaminase (SEQ ID NO: 1452).

  The protein alanine aminotransferase is known or considered to have the following functions: It is also involved in cellular nitrogen metabolism and hepatic gluconeogenesis initiated from precursors transported from skeletal muscle. The sequence of the protein alanine aminotransferase is shown at the end of the application as "alanine aminotransferase amino acid sequence". Known polymorphisms of this sequence are shown in Table 1002.

  Localization of the protein alanine aminotransferase is considered to be a protoplast.

  Cluster R35137 can be used as a diagnostic marker by overexpression of transcripts of this cluster in cancer. The expression of such transcripts in normal tissues is also shown by the method previously described. The term “number” in the right column of the table and the number on the y-axis of FIG. 34 refer to the weighted expression of ESTs in each category as “ppm” (the ppm of ESTs of a particular cluster in this category by ppm Ratio of expression to expression of all ESTs).

  As shown generally for the histograms in FIG. 34 and Table 1003, the following results were obtained. This cluster was overexpressed (at least at minimal levels) in the following pathological conditions: hepatocellular carcinoma.

  As mentioned above, cluster R35137 is characterized by the six transcripts listed in Table 1 above. These transcripts encode proteins which are variants of the protein alanine aminotransferase. A description of each mutein of the invention is provided herein.

  The mutein R35137_PEA_1_PEA_1_PEA_1_P9 according to the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript R35137_PEA_1_PEA_1_PEA_1_T10. An alignment to a known protein (alanine aminotransferase) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of the comparison between R35137_PEA_1_PEA_1_PEA_1_P9 and ALAT_HUMAN_V1 (SEQ ID NO: 1453) Corresponding to amino acids 1 to 274 of ALAT_HUMAN_V1, corresponding to amino acids 1 to 274 of R35137_PEA_1_PEA_1_PEA_1_P9 MASSTGDRSQAVRHGLRAKVLTLDGMNPRVRRVEYAVRGPIVQRALELEQELRQGVKKPFTEVIRANIGDAQAMGQRPITFLRQVLALCVNPDLLSSPNFPDDAKKRAERILQACGGHSLGAYSVSSGIQLIREDVARYIERRDGGIPADPNNVFLSTGASDAIVTVLKLLVAGEGHTRTGVLIPIPQYPLYSATLAELGAVQVDYYLDEERAWALDVAELHRALGQARDHCRPRALCVINPGNPTGQVQTRECIEAVIRFA A first amino acid sequence that is at least 90% homologous to EERLFLLADEV and a sequence corresponding to amino acids 275-385 of R35137_PEA_1_PEA_1_PEA_1_P9. R35 comprises a second amino acid sequence which is at least 90%, most preferably at least 95% homologous, said first amino acid sequence and said second amino acid sequence being adjacent and in sequential order, R35 Isolated chimeric polypeptide encoding 37_PEA_1_PEA_1_PEA_1_P9.

  2. In the library of at least 70%, at least about 70%, at least about 70%, at least about 70%. An isolated polypeptide encoding a tail.

  It should be noted that the known protein sequence (ALAT_HUMAN) has one or more changes from the sequence shown at the end of the application and this amino acid sequence is designated as ALAT_HUMAN_V1. The occurrence of these changes was previously known and listed in the following table.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: Intracellular. Protein localization is considered to be intracellular as no transmembrane domain estimation program will deduce that this protein is a transmembrane domain. Furthermore, both signal peptide deducing programs deduce that this protein is a non-secretory protein.

  The mutein R35137_PEA_1_PEA_1_PEA_1_P9 is encoded by the following transcript: R35137_PEA_1_PEA_1_PEA_1_T10 (sequences shown at the end of the application). The code portion of the transcript R35137_PEA_1_PEA_1_PEA_1_T10 is shown in bold, starting from position 271 and ending at position 1425. The transcript also has the following SNPs listed in Table 1006 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, a mutein, The presence of known SNPs in the R35137_PEA_1_PEA_1_PEA_1_P9 sequence supports the predicted sequence of this mutant protein of the invention).

  The mutein R35137_PEA_1_PEA_1_PEA_1_P8 according to the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript R35137_PEA_1_PEA_1_PEA_1_T11. An alignment to a known protein (alanine aminotransferase) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between R35137_PEA_1_PEA_1_PEA_1_P8 and ALAT_HUMAN_V1. Corresponding to amino acids 1 to 320 of ALAT_HUMAN_V1, corresponding to amino acids 1 to 320 of R35137_PEA_1_PEA_1_PEA_1_P8 MASSTGDRSQAVRHGLRAKVLTLDGMNPRVRRVEYAVRGPIVQRALELEQELRQGVKKPFTEVIRANIGDAQAMGQRPITFLRQVLALCVNPDLLSSPNFPDDAKKRAERILQACGGHSLGAYSVSSGIQLIREDVARYIERRDGGIPADPNNVFLSTGASDAIVTVLKLLVAGEGHTRTGVLIPIPQYPLYSATLAELGAVQVDYYLDEERAWALDVAELHRALGQARDHCRPRALCVINPGNPTGQVQTRECIEAVIRFA EERLFLLADEVYQDNVYAAGSQFHSFKKVLMEMGPPYAGQQELASFHSTSKGYMGEC A polypeptide with the first amino acid sequence that is at least 90% homologous to RPR 35137_PEA_1_PEA_1_PEA_1_P8 and the sequence VRTRRVGARGPWPGPPRPMGHPLLRT corresponding to amino acids 321-346 and at least 80% to 70% Comprises R35137_PEA_1_PEA_1_PEA_1_P8, which comprises a second amino acid sequence which is at least 90%, most preferably at least 95% homologous, said first and second amino acid sequences being adjacent and in sequential order Isolated chimera polypep De.

  2. R35137_PEA_1_PEA_1_P8 comprising a polypeptide at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence VRTRRVGARGPWPGPPRPMGHPLLRT in An isolated polypeptide encoding a tail.

  It should be noted that the known protein sequence (ALAT_HUMAN) has one or more changes from the sequence shown at the end of the application and this amino acid sequence is designated as ALAT_HUMAN_V1. The occurrence of these changes was previously known and listed in the following table.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: Intracellular. Protein localization is considered to be intracellular as no transmembrane domain estimation program will deduce that this protein is a transmembrane domain. Furthermore, both signal peptide deducing programs deduce that this protein is a non-secretory protein.

  The mutein R35137_PEA_1_PEA_1_PEA_1_P8 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, enumerating other amino acids, the last column lists the SNPs as shown in Table 1008) It indicates whether it is known and the presence of a known SNP in the mutein R35137_PEA_1_PEA_1_PEA_1_P8 sequence supports the predicted sequence of this mutein of the invention).

  The mutein R35137_PEA_1_PEA_1_PEA_1_P8 is encoded by the following transcript: R35137_PEA_1_PEA_1_PEA_1_T11 (sequences shown at the end of the application). The code portion of the transcript R35137_PEA_1_PEA_1_PEA_1_T11 is shown in bold, starting from position 271 and ending at position 1308. The transcript also has the following SNPs listed in Table 1009 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, a mutein, The presence of known SNPs in the R35137_PEA_1_PEA_1_PEA_1_P8 sequence supports the putative sequence of this mutant protein of the invention).

  The mutein R35137_PEA_1_PEA_1_PEA_1_P11 of the present invention has the amino acid sequence shown at the end of the application and is encoded by the transcript R35137_PEA_1_PEA_1_PEA_1_T14. An alignment to a known protein (alanine aminotransferase) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between R35137_PEA_1_PEA_1_PEA_1_P11 and ALAT_HUMAN_V1. Corresponding to amino acids 1-229 of ALAT_HUMAN_V1, first amino acid sequence at least 90% homologous to the corresponding MASSTGDRSQAVRHGLRAKVLTLDGMNPRVRRVEYAVRGPIVQRALELEQELRQGVKKPFTEVIRANIGDAQAMGQRPITFLRQVLALCVNPDLLSSPNFPDDAKKRAERILQACGGHSLGAYSVSSGIQLIREDVARYIERRDGGIPADPNNVFLSTGASDAIVTVLKLLVAGEGHTRTGVLIPIPQYPLYSATLAELGAVQVDYYLDEERAWALDVAELHRALGQAR to amino acids 1-229 of R35137_PEA_1_PEA_1_PEA_1_P11, ALAT_HUMA The first amino acid sequence and the second amino acid sequence contain a second amino acid sequence that is at least 90% homologous to SGFGQREGTY HFPLTIKLPLLELLLELSLRFHAKFTLEYS corresponding to amino acids 455 to 496 of V1 and also to amino acids 230 to 271 of R35137 PEA1 _PEA1 _PEA1_P11. An isolated chimeric polypeptide encoding R35137_PEA_1_PEA_1_PEA_1_P11, adjacent and in sequential order.

  2. Length “n” (wherein n is at least about 10 amino acids long, optionally at least about 20 amino acids long, preferably at least about 30 amino acids long, more preferably at least about 40 amino acids long, most preferably at least about 50 amino acids in length, at least two amino acids comprising RS, starting from any of the following structures: amino acid numbers 229-x to 229, amino acid numbers 230 + ((n-2) -x) (formula An isolated chimeric polypeptide encoding a rim portion of R35137_PEA_1_PEA_1_PEA_1_P11, comprising a polypeptide having a sequence terminating in: x) varying from 0 to n-2).

  It should be noted that the known protein sequence (ALAT_HUMAN) has one or more changes from the sequence shown at the end of the application and this amino acid sequence is designated as ALAT_HUMAN_V1. The occurrence of these changes was previously known and listed in the following table.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: Intracellular. Protein localization is considered to be intracellular as no transmembrane domain estimation program will deduce that this protein is a transmembrane domain. Furthermore, both signal peptide deducing programs deduce that this protein is a non-secretory protein.

  The mutein R35137_PEA_1_PEA_1_PEA_1_P11 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, the last column lists the SNPs as shown in Table 1011) It indicates whether it is known and the presence of a known SNP in the mutein R35137_PEA_1_PEA_1_PEA_1_P11 sequence supports the predicted sequence of this mutein of the invention).

  The mutein R35137_PEA_1_PEA_1_PEA_1_P11 is encoded by the following transcript: R35137_PEA_1_PEA_1_PEA_1_T14 (sequences shown at the end of the application). The code portion of the transcript R35137_PEA_1_PEA_1_PEA_1_T14 is shown in bold, starting from position 271 and ending at position 1083. The transcript also has the following SNPs listed in Table 1012 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, a mutein, The presence of known SNPs in the R35137_PEA_1_PEA_1_PEA_1_P11 sequence supports the predicted sequence of this mutant protein of the invention).

  The mutein R35137_PEA_1_PEA_1_PEA_1_P2 according to the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript R35137_PEA_1_PEA_1_PEA_1_T3. An alignment to a known protein (alanine aminotransferase) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between R35137_PEA_1_PEA_1_PEA_1_P2 and ALAT_HUMAN_V1. Corresponding to amino acids 1 to 274 of ALAT_HUMAN_V1, corresponding to amino acids 1 to 274 of R35137_PEA_1_PEA_1_PEA_1_P2 MASSTGDRSQAVRHGLRAKVLTLDGMNPRVRRVEYAVRGPIVQRALELEQELRQGVKKPFTEVIRANIGDAQAMGQRPITFLRQVLALCVNPDLLSSPNFPDDAKKRAERILQACGGHSLGAYSVSSGIQLIREDVARYIERRDGGIPADPNNVFLSTGASDAIVTVLKLLVAGEGHTRTGVLIPIPQYPLYSATLAELGAVQVDYYLDEERAWALDVAELHRALGQARDHCRPRALCVINPGNPTGQVQTRECIEAVIRFA A sequence of RGAGEREAGQQSAPVTPCALPGVPGQRVRRGFAPLGALGRAGL LQLGHGRVPRRLCGGEGHHIGAC I, a sequence corresponding to amino acids 275-399 of R35137_PEA_1_PEA_1_PEA_1_P2 that is at least 90% homologous to EERL FLLA DEV. Comprises a second amino acid sequence which is at least 90%, most preferably at least 95% homologous, said first amino acid sequence and the second amino acid sequence being contiguous and In consecutive order, isolated chimeric polypeptide coding R35137_PEA_1_PEA_1_PEA_1_P2.

  2. In the group of the ssssssssssed in the ssssssssssssseness at the end of the sss. An isolated polypeptide encoding a tail.

  It should be noted that the known protein sequence (ALAT_HUMAN) has one or more changes from the sequence shown at the end of the application and this amino acid sequence is designated as ALAT_HUMAN_V1. The occurrence of these changes was previously known and listed in the following table.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: Intracellular. Protein localization is considered to be intracellular as no transmembrane domain estimation program will deduce that this protein is a transmembrane domain. Furthermore, both signal peptide deducing programs deduce that this protein is a non-secretory protein.

  The mutein R35137_PEA_1_PEA_1_PEA_1_P2 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, enumerating other amino acids, the last column lists the SNPs as shown in Table 1014) It indicates whether it is known and the presence of a known SNP in the mutein R35137_PEA_1_PEA_1_PEA_1_P2 sequence supports the putative sequence of this mutein of the invention).

  The mutein R35137_PEA_1_PEA_1_PEA_1_P2 is encoded by the following transcript: R35137_PEA_1_PEA_1_PEA_1_T3 (sequences shown at the end of the application). The code portion of the transcript R35137_PEA_1_PEA_1_PEA_1_T3 is shown in bold, starting from position 271 and ending at position 1467. The transcript also has the following SNPs listed in Table 1015 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, a mutein, The presence of known SNPs in the R35137_PEA_1_PEA_1_PEA_1_P2 sequence supports the predicted sequence of this mutant protein of the invention).

  The mutein R35137_PEA_1_PEA_1_PEA_1_P4 according to the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript R35137_PEA_1_PEA_1_PEA_1_T5. An alignment to a known protein (alanine aminotransferase) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between R35137_PEA_1_PEA_1_PEA_1_P4 and ALAT_HUMAN_V1. Corresponding to amino acids 1 to 494 of ALAT_HUMAN_V1, corresponding to amino acids 1 to 494 of R35137_PEA_1_PEA_1_PEA_1_P4 MASSTGDRSQAVRHGLRAKVLTLDGMNPRVRRVEYAVRGPIVQRALELEQELRQGVKKPFTEVIRANIGDAQAMGQRPITFLRQVLALCVNPDLLSSPNFPDDAKKRAERILQACGGHSLGAYSVSSGIQLIREDVARYIERRDGGIPADPNNVFLSTGASDAIVTVLKLLVAGEGHTRTGVLIPIPQYPLYSATLAELGAVQVDYYLDEERAWALDVAELHRALGQARDHCRPRALCVINPGNPTGQVQTRECIEAVIRFA The first amino acid sequence at least 90% homologous to IiarueruefueruerueidiibuiwaikyudienubuiwaieieijiesukyuefueichiesuefukeikeibuieruemuiemuJipiPiwaieijikyukyuierueiesuefueichiesutiesukeijiwaiemujiishijiefuarujijiwaibuiibuibuienuemudieieibuikyukyukyuemuerukeieruemuesubuiaruerushiPiPibuiPijikyueieruerudierubuibuiesupipiEipitidiPiesuefueikyuefukyueiikeikyueibuierueiierueieikeieikeierutiikyubuiefuenuieiPijiaiesushienuPibuikyujieiemuwaiesuefuPiarubuikyueruPiPiarueibuiiarueikyuierujierueiPidiemuefuefushieruaruerueruiitijiaishibuibuiPijiesujiefujikyuaruijitiwaieichiefuaruemutiILPPLEKLRLLLEKLSRFHAKFTLE, sequence SPGRLWSPLYLLLMPGGVGWGGCWAPASLQVP corresponding to amino acids 495-555 of R35137_PEA_1_PEA_1_PEA_1_P4 A polypeptide having KAVWQSDSKKEALAAAWPAPTCLPFQA and a second amino acid sequence which is at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous; An isolated chimeric polypeptide encoding R35137_PEA_1_PEA_1_PEA_1_P4, wherein the amino acid sequence of 1 and the second amino acid sequence are adjacent and in sequential order.

  2. A sequence of at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95%, preferably at least about 95%, An isolated polypeptide encoding a tail.

  It should be noted that the known protein sequence (ALAT_HUMAN) has one or more changes from the sequence shown at the end of the application and this amino acid sequence is designated as ALAT_HUMAN_V1. The occurrence of these changes was previously known and listed in the following table.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: Intracellular. Protein localization is considered to be intracellular as no transmembrane domain estimation program will deduce that this protein is a transmembrane domain. Furthermore, both signal peptide deducing programs deduce that this protein is a non-secretory protein.

  The mutein R35137_PEA_1_PEA_1_PEA_1_P4 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing the other amino acids, and listing the other amino acids, as shown in Table 1017; It indicates whether it is known and the presence of a known SNP in the mutein R35137_PEA_1_PEA_1_PEA_1_P4 sequence supports the putative sequence of this mutein of the invention).

  The mutein R35137_PEA_1_PEA_1_PEA_1_P4 is encoded by the following transcript: R35137_PEA_1_PEA_1_PEA_1_T5 (sequences shown at the end of the application). The code portion of the transcript R35137_PEA_1_PEA_1_PEA_1_T5 is shown in bold, starting from position 271 and ending at position 1935. The transcript also has the following SNPs listed in Table 1018 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, a mutein, The presence of known SNPs in the R35137_PEA_1_PEA_1_PEA_1_P4 sequence supports the predicted sequence of this mutant protein of the invention).

  As mentioned above, cluster R35137 is characterized by the 20 segments listed in Table 2 above, the sequence of which is shown at the end of the application. These segments are part of the nucleic acid sequence, which are of particular interest and are individually described herein. A description of each segment of the invention is provided herein.

  The segment cluster R35137_PEA_1_PEA_1_PEA_1_node_2 of the present invention is supported by 19 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: R35137_PEA_1_PEA_1_PEA_1_T3, R35137_PEA_1_PEA_1_PEA_1_T5, R35137_PEA_1_PEA_1_PEA_1_PEA_1_PEA_1_PEA_1_PEA_1_T11, R3514_14_14_14_14_14_14_14_14_14 Table 1019 below describes the start and end positions of this segment on each transcript.

  The segment cluster R35137_PEA_1_PEA_1_PEA_1_node_3 of the present invention is supported by 24 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: R35137_PEA_1_PEA_1_PEA_1_T3, R35137_PEA_1_PEA_1_PEA_1_T5, R35137_PEA_1_PEA_1_PEA_1_PEA_1_PEA_1_PEA_1_PEA_1_T11, R3514_14_14_14_14_14_14_14_14_14 Table 1020 below describes the start and end positions of this segment on each transcript.

  The segment cluster R35137_PEA_1_PEA_1_PEA_1_node_9 of the present invention is supported by 25 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: R35137_PEA_1_PEA_1_PEA_1_T3, R35137_PEA_1_PEA_1_PEA_1_T5, R35137_PEA_1_PEA_1_PEA_1_PEA_1_PEA_1_PEA_1_PEA_1_T11, R3514_14_14_14_14_14_14_14_14_14 Table 1021 below describes the start and end positions of this segment on each transcript.

  The segment cluster R35137_PEA_1_PEA_1_PEA_1_node_11 of the present invention is supported by 30 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: R35137_PEA_1_PEA_1_PEA_1_T3, R35137_PEA_1_PEA_1_PEA_1_T5, R35137_PEA_1_PEA_1_PEA_1_PEA_1_PEA_1_PEA_1_PEA_1_T11, R3514_14_14_14_14_14_14_14_14_14 Table 1022 below describes the start and end positions of this segment on each transcript.

  The segment cluster R35137_PEA_1_PEA_1_PEA_1_node_16 of the present invention is supported by 23 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: R35137_PEA_1_PEA_1_PEA_1_T3, R35137_PEA_1_PEA_1_PEA_1_T5, R35137_PEA_1_PEA_1_PEA_1_T10, R35137_PEA_1_PEA_1_PEA_1_PEA_1_T11, _1_14PE_14E Table 1023 below describes the start and end positions of this segment on each transcript.

  The segment cluster R35137_PEA_1_PEA_1_PEA_1_node_18 of the present invention is supported by 24 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: R35137_PEA_1_PEA_1_PEA_1_T3, R35137_PEA_1_PEA_1_PEA_1_T5, R35137_PEA_1_PEA_1_PEA_1_T10, R35137_PEA_1_PEA_1_PEA_1_PEA_1_T11, _1_14PE_14E Table 1024 below lists the start and end positions of this segment on each transcript.

  Microarray (chip) data for this segment is also available, as follows. As described above, with respect to the clusters themselves, different oligonucleotides were tested for differential expression in different disease states, in particular cancer. The following oligonucleotides were found to reach this segment (for lung cancer) (shown in Table 1025).

  The segment cluster R35137_PEA_1_PEA_1_PEA_1_node_20 of the present invention is supported by 29 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: R35137_PEA_1_PEA_1_PEA_1_T3, R35137_PEA_1_PEA_1_PEA_1_T5, R35137_PEA_1_PEA_1_PEA_1_T10, R35137_PEA_1_PEA_1_PEA_1_PEA_1_T11, _1_14PE_14E Table 1026 below describes the start and end positions of this segment on each transcript.

  The segment cluster R35137_PEA_1_PEA_1_PEA_1_node_27 of the present invention is supported by 39 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: R35137_PEA_1_PEA_1_PEA_1_T3, R35137_PEA_1_PEA_1_PEA_1_T5, R35137_PEA_1_PEA_1_PEA_1_PEA_1_PEA_1_PEA_1_PEA_1_T11, R3514_14_14_14_14_14_14_14_14_14 Table 1027 below describes the start and end positions of this segment on each transcript.

  According to an optional embodiment of the present invention, there is also provided a short segment associated with the above cluster. These segments are up to about 120 bp in length and are therefore included in the individual descriptions.

  The segment cluster R35137_PEA_1_PEA_1_PEA_1_node_5 of the present invention is supported by 20 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: R35137_PEA_1_PEA_1_PEA_1_T3, R35137_PEA_1_PEA_1_PEA_1_T5, R35137_PEA_1_PEA_1_PEA_1_PEA_1_PEA_1_PEA_1_PEA_1_T11, R3514_14_14_14_14_14_14_14_14_14 Table 1028 below describes the start and end positions of this segment on each transcript.

  The segment cluster R35137_PEA_1_PEA_1_PEA_1_node_7 of the present invention is supported by 23 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: R35137_PEA_1_PEA_1_PEA_1_T3, R35137_PEA_1_PEA_1_PEA_1_T5, R35137_PEA_1_PEA_1_PEA_1_PEA_1_PEA_1_PEA_1_PEA_1_T11, R3514_14_14_14_14_14_14_14_14_14 Table 1029 below describes the start and end positions of this segment on each transcript.

  The segment cluster R35137_PEA_1_PEA_1_PEA_1_node_12 of the present invention is supported by 22 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: R35137_PEA_1_PEA_1_PEA_1_T3, R35137_PEA_1_PEA_1_PEA_1_T5, R35137_PEA_1_PEA_1_PEA_1_T10, R35137_PEA_1_PEA_1_PEA_1_PEA_1_T11, _1_14PE_14E Table 1030 below describes the start and end positions of this segment on each transcript.

  The segment cluster R35137_PEA_1_PEA_1_PEA_1_node_14 of the present invention is supported by 23 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: R35137_PEA_1_PEA_1_PEA_1_T3, R35137_PEA_1_PEA_1_PEA_1_T5, R35137_PEA_1_PEA_1_PEA_1_T10, R35137_PEA_1_PEA_1_PEA_1_PEA_1_T11, _1_14PE_14E Table 1031 below describes the start and end positions of this segment on each transcript.

  The segment cluster R35137_PEA_1_PEA_1_PEA_1_node_15 of the present invention is supported by six libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: R35137_PEA_1_PEA_1_PEA_1_T3, R35137_PEA_1_PEA_1_PEA_1_T10, and R35137_PEA_1_PEA_1_PEA_1_T12. Table 1032 below describes the start and end positions of this segment on each transcript.

  The segment cluster R35137_PEA_1_PEA_1_PEA_1_node_17 of the present invention is supported by 5 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: R35137_PEA_1_PEA_1_PEA_1_T10, R35137_PEA_1_PEA_1_PEA_1_T11, and R35137_PEA_1_PEA_1_PEA_1_T12. Table 1033 below describes the start and end positions of this segment on each transcript.

  The segment cluster R35137_PEA_1_PEA_1_PEA_1_node_21 of the present invention is supported by six libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R35137_PEA_1_PEA_1_PEA_1_T11 and R35137_PEA_1_PEA_1_PEA_1_T12. Table 1034 below describes the start and end positions of this segment on each transcript.

  The segment cluster R35137_PEA_1_PEA_1_PEA_1_node_22 of the present invention is supported by 31 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: R35137_PEA_1_PEA_1_PEA_1_T3, R35137_PEA_1_PEA_1_PEA_1_T5, R35137_PEA_1_PEA_1_PEA_1_T10, R35137_PEA_1_PEA_1_PEA_1_PEA_1_T11, _1_14PE_14E Table 1035 below describes the start and end positions of this segment on each transcript.

  The segment cluster R35137_PEA_1_PEA_1_PEA_1_node_23 of the present invention is supported by 29 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: R35137_PEA_1_PEA_1_PEA_1_T3, R35137_PEA_1_PEA_1_PEA_1_T5, R35137_PEA_1_PEA_1_PEA_1_PEA_1_PEA_1_PEA_1_PEA_1_T11, R3514_14_14_14_14_14_14_14_14_14 Table 1036 below describes the start and end positions of this segment on each transcript.

  The segment cluster R35137_PEA_1_PEA_1_PEA_1_node_24 of the present invention is supported by 5 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R35137_PEA_1_PEA_1_PEA_1_T11 and R35137_PEA_1_PEA_1_PEA_1_T12. Table 1037 below describes the start and end positions of this segment on each transcript.

  The segment cluster R35137_PEA_1_PEA_1_PEA_1_node_25 of the present invention is supported by 30 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: R35137_PEA_1_PEA_1_PEA_1_T3, R35137_PEA_1_PEA_1_PEA_1_T5, R35137_PEA_1_PEA_1_PEA_1_PEA_1_PEA_1_PEA_1_PEA_1_T11, R3514_14_14_14_14_14_14_14_14_14 Table 1038 below describes the start and end positions of this segment on each transcript.

  The segment cluster R35137_PEA_1_PEA_1_PEA_1_node_26 of the present invention is supported by 29 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: R35137_PEA_1_PEA_1_PEA_1_T3, R35137_PEA_1_PEA_1_PEA_1_T10, R35137_PEA_1_PEA_1_PEA_1_T11, R35137_PEA_1_PEA_1_PEA_1_PEA_1_T12, R_35_14_E_14. Table 1039 below describes the start and end positions of this segment on each transcript.

Mutated protein alignment against previously known proteins:

Sequence name: ALAT_HUMAN_V1



Sequence documentation:



Alignment of: R35137_PEA_1_PEA_1_PEA_1_P9 x ALAT_HUMAN_V1 ..



Alignment segment 1/1:



Quality: 2619.00 Escore: 0

Matching length: 274 Total length: 274

Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00

Total Percent Similarity: 100.00 Total Percent Identity: 100.00

Gaps: 0



Alignment:

....

1 MASSTGDRSQAVRLGLRAKVLTLDMMNPRVRVEYAVRGPIVQRALELEQ 50

||||||||||||||||||||||||||||||||||||||||

1 MASSTGDRSQAVRLGLRAKVLTLDMMNPRVRVEYAVRGPIVQRALELEQ 50

....

51 ELRQGVKKPFTEVIRANIGDAQAMGQRPITFLRQ VLALCVNPDLLSSPNF 100

||||||||||||||||||||||||||||||||||||||||

51 ELRQGVKKPFTEVIRANIGDAQAMGQRPITFLRQ VLALCVNPDLLSSPNF 100

....

101 PDDAKKRAERILQACGGHSLGAYSSSSGIQRIDVARYIERRDGGIPAD 150

||||||||||||||||||||||||||||||||||||||||

101 PDDAKKRAERILQACGGHSLGAYSSSSGIQRIDVARYIERRDGGIPAD 150

....

151 PNNVFLSTGASDAIVTVLVKLLVAGEGHTRTGVLIPIPQYPLYSATLAELG 200

||||||||||||||||||||||||||||||||||||||||

151 PNNVFLSTGASDAIVTVLVKLLVAGEGHTRTGVLIPIPQYPLYSATLAELG 200

....

201 AVQVDYYLDEERAWALDVAELHRALGQARDHCRPRALCVINPGNPTGQVQ 250

||||||||||||||||||||||||||||||||||||||||

201 AVQVDYYLDEERAWALDVAELHRALGQARDHCRPRALCVINPGNPTGQVQ 250

.

251 TRECIEAVIRFAFEERLFLADEV 274

|||||||||||||||||||||||

251 TRECIEAVIRFAFEERLFLADEV 274













Sequence name: ALAT_HUMAN_V1



Sequence documentation:



Alignment of: R35137_PEA_1_PEA_1_PEA_1_P8 x ALAT_HUMAN_V1 ..



Alignment segment 1/1:



Quality: 3088.00 Escore: 0

Matching length: 320 Total length: 320

Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00

Total Percent Similarity: 100.00 Total Percent Identity: 100.00

Gaps: 0



Alignment:

....

1 MASSTGDRSQAVRLGLRAKVLTLDMMNPRVRVEYAVRGPIVQRALELEQ 50

||||||||||||||||||||||||||||||||||||||||

1 MASSTGDRSQAVRLGLRAKVLTLDMMNPRVRVEYAVRGPIVQRALELEQ 50

....

51 ELRQGVKKPFTEVIRANIGDAQAMGQRPITFLRQ VLALCVNPDLLSSPNF 100

||||||||||||||||||||||||||||||||||||||||

51 ELRQGVKKPFTEVIRANIGDAQAMGQRPITFLRQ VLALCVNPDLLSSPNF 100

....

101 PDDAKKRAERILQACGGHSLGAYSSSSGIQRIDVARYIERRDGGIPAD 150

||||||||||||||||||||||||||||||||||||||||

101 PDDAKKRAERILQACGGHSLGAYSSSSGIQRIDVARYIERRDGGIPAD 150

....

151 PNNVFLSTGASDAIVTVLVKLLVAGEGHTRTGVLIPIPQYPLYSATLAELG 200

||||||||||||||||||||||||||||||||||||||||

151 PNNVFLSTGASDAIVTVLVKLLVAGEGHTRTGVLIPIPQYPLYSATLAELG 200

....

201 AVQVDYYLDEERAWALDVAELHRALGQARDHCRPRALCVINPGNPTGQVQ 250

||||||||||||||||||||||||||||||||||||||||

201 AVQVDYYLDEERAWALDVAELHRALGQARDHCRPRALCVINPGNPTGQVQ 250

....

251 TRECIEAVIRF AFEERLFLLA DEVY QDNVYAAGSQFHSFKKVLMEMGPPY 300

||||||||||||||||||||||||||||||||||||||||

251 TRECIEAVIRF AFEERLFLLA DEVY QDNVYAAGSQFHSFKKVLMEMGPPY 300

.

301 AGQQELASFHSTSKGYMGEC 320

|||||||||||||||||||

301 AGQQELASFHSTSKGYMGEC 320













Sequence name: ALAT_HUMAN_V1



Sequence documentation:



Alignment of: R35137_PEA_1_PEA_1_PEA_1_P11 x ALAT_HUMAN_V1 ..



Alignment segment 1/1:



Quality: 2487.00 Escore: 0

Matching length: 271 Total length: 496

Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00

Total Percent Similarity: 54.64 Total Percent Identity: 54.64

Gaps: 1



Alignment:

....

1 MASSTGDRSQAVRLGLRAKVLTLDMMNPRVRVEYAVRGPIVQRALELEQ 50

||||||||||||||||||||||||||||||||||||||||

1 MASSTGDRSQAVRLGLRAKVLTLDMMNPRVRVEYAVRGPIVQRALELEQ 50

....

51 ELRQGVKKPFTEVIRANIGDAQAMGQRPITFLRQ VLALCVNPDLLSSPNF 100

||||||||||||||||||||||||||||||||||||||||

51 ELRQGVKKPFTEVIRANIGDAQAMGQRPITFLRQ VLALCVNPDLLSSPNF 100

....

101 PDDAKKRAERILQACGGHSLGAYSSSSGIQRIDVARYIERRDGGIPAD 150

||||||||||||||||||||||||||||||||||||||||

101 PDDAKKRAERILQACGGHSLGAYSSSSGIQRIDVARYIERRDGGIPAD 150

....

151 PNNVFLSTGASDAIVTVLVKLLVAGEGHTRTGVLIPIPQYPLYSATLAELG 200

||||||||||||||||||||||||||||||||||||||||

151 PNNVFLSTGASDAIVTVLVKLLVAGEGHTRTGVLIPIPQYPLYSATLAELG 200

....

201 AVQVDYYLDEERAWALDVAELHRALGQAR ......... 229

|||||||||||||||||||||||||||

201 AVQVDYYLDEERAWALDVAELHRALGQARDHCRPRALCVINPGNPTGQVQ 250

....

229 ...................................................... .



251 TRECIEAVIRF AFEERLFLLA DEVY QDNVYAAGSQFHSFKKVLMEMGPPY 300

....

229 ...................................................... .



301 AGQQELASFHSTSKGYMGECGFRGGYVEVVNMDAAVQQQMLKLMSVRLCP 350

....

229 ...................................................... .



351 PVPGQALLDLVVSPPAPTDPSFAQFQAEKQAVLAELAAKATLTEQVFNEA 400

....

229 ...................................................... .



401 PGISCNPVQGAMYSFPRVQLPPRAVERAQELGLAPDMMFCLLRLLEETGIC 450

....

230 .... SGFGQREGTYHFRMTILPPLEKRLRLLESKLSRFHAKFTLEYS 271

|||||||||||||||||||||||||||||||||||||

451 VVPGSGFGQREGTYHFRMTILPPLKLRLLELKLSRFHAKFTLEYS 496













Sequence name: ALAT_HUMAN_V1



Sequence documentation:



Alignment of: R35137_PEA_1_PEA_1_PEA_1_P2 x ALAT_HUMAN_V1 ..



Alignment segment 1/1:



Quality: 2619.00 Escore: 0

Matching length: 274 Total length: 274

Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00

Total Percent Similarity: 100.00 Total Percent Identity: 100.00

Gaps: 0



Alignment:

....

1 MASSTGDRSQAVRLGLRAKVLTLDMMNPRVRVEYAVRGPIVQRALELEQ 50

||||||||||||||||||||||||||||||||||||||||

1 MASSTGDRSQAVRLGLRAKVLTLDMMNPRVRVEYAVRGPIVQRALELEQ 50

....

51 ELRQGVKKPFTEVIRANIGDAQAMGQRPITFLRQ VLALCVNPDLLSSPNF 100

||||||||||||||||||||||||||||||||||||||||

51 ELRQGVKKPFTEVIRANIGDAQAMGQRPITFLRQ VLALCVNPDLLSSPNF 100

....

101 PDDAKKRAERILQACGGHSLGAYSSSSGIQRIDVARYIERRDGGIPAD 150

||||||||||||||||||||||||||||||||||||||||

101 PDDAKKRAERILQACGGHSLGAYSSSSGIQRIDVARYIERRDGGIPAD 150

....

151 PNNVFLSTGASDAIVTVLVKLLVAGEGHTRTGVLIPIPQYPLYSATLAELG 200

||||||||||||||||||||||||||||||||||||||||

151 PNNVFLSTGASDAIVTVLVKLLVAGEGHTRTGVLIPIPQYPLYSATLAELG 200

....

201 AVQVDYYLDEERAWALDVAELHRALGQARDHCRPRALCVINPGNPTGQVQ 250

||||||||||||||||||||||||||||||||||||||||

201 AVQVDYYLDEERAWALDVAELHRALGQARDHCRPRALCVINPGNPTGQVQ 250

.

251 TRECIEAVIRFAFEERLFLADEV 274

|||||||||||||||||||||||

251 TRECIEAVIRFAFEERLFLADEV 274













Sequence name: ALAT_HUMAN_V1



Sequence documentation:



Alignment of: R35137_PEA_1_PEA_1_PEA_1_P4 x ALAT_HUMAN_V1 ..



Alignment segment 1/1:



Quality: 4785.00 Escore: 0

Matching length: 494 Total length: 494

Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00

Total Percent Similarity: 100.00 Total Percent Identity: 100.00

Gaps: 0



Alignment:

....

1 MASSTGDRSQAVRLGLRAKVLTLDMMNPRVRVEYAVRGPIVQRALELEQ 50

||||||||||||||||||||||||||||||||||||||||

1 MASSTGDRSQAVRLGLRAKVLTLDMMNPRVRVEYAVRGPIVQRALELEQ 50

....

51 ELRQGVKKPFTEVIRANIGDAQAMGQRPITFLRQ VLALCVNPDLLSSPNF 100

||||||||||||||||||||||||||||||||||||||||

51 ELRQGVKKPFTEVIRANIGDAQAMGQRPITFLRQ VLALCVNPDLLSSPNF 100

....

101 PDDAKKRAERILQACGGHSLGAYSSSSGIQRIDVARYIERRDGGIPAD 150

||||||||||||||||||||||||||||||||||||||||

101 PDDAKKRAERILQACGGHSLGAYSSSSGIQRIDVARYIERRDGGIPAD 150

....

151 PNNVFLSTGASDAIVTVLVKLLVAGEGHTRTGVLIPIPQYPLYSATLAELG 200

||||||||||||||||||||||||||||||||||||||||

151 PNNVFLSTGASDAIVTVLVKLLVAGEGHTRTGVLIPIPQYPLYSATLAELG 200

....

201 AVQVDYYLDEERAWALDVAELHRALGQARDHCRPRALCVINPGNPTGQVQ 250

||||||||||||||||||||||||||||||||||||||||

201 AVQVDYYLDEERAWALDVAELHRALGQARDHCRPRALCVINPGNPTGQVQ 250

....

251 TRECIEAVIRF AFEERLFLLA DEVY QDNVYAAGSQFHSFKKVLMEMGPPY 300

||||||||||||||||||||||||||||||||||||||||

251 TRECIEAVIRF AFEERLFLLA DEVY QDNVYAAGSQFHSFKKVLMEMGPPY 300

....

301 AGQQELASFHSTSKGYMGECGFRGGYVEVVNMDAAVQQQMLKLMSVRLCP 350

||||||||||||||||||||||||||||||||||||||||

301 AGQQELASFHSTSKGYMGECGFRGGYVEVVNMDAAVQQQMLKLMSVRLCP 350

....

351 PVPGQALLDLVVSPPAPTDPSFAQFQAEKQAVLAELAAKATLTEQVFNEA 400

||||||||||||||||||||||||||||||||||||||||

351 PVPGQALLDLVVSPPAPTDPSFAQFQAEKQAVLAELAAKATLTEQVFNEA 400

....

401 PGISCNPVQGAMYSFPRVQLPPRAVERAQELGLAPDMMFCLLRLLEETGIC 450

||||||||||||||||||||||||||||||||||||||||

401 PGISCNPVQGAMYSFPRVQLPPRAVERAQELGLAPDMMFCLLRLLEETGIC 450

....

451 VVPGSGFGQREGTYHFRMTILPPLEKRLLLEKLSRFHAKFTTLE 494

||||||||||||||||||||||||||||||||||||||

451 VVPGSGFGQREGTYHFRMTILPPLEKRLLLEKLSRFHAKFTTLE 494

Description of cluster Z25299 Cluster Z25299 is characterized by 5 transcripts and 11 segments of interest, the names of which are given in Tables 1040 and 1041, respectively, and the sequence itself is given at the end of the application. Selected protein variants are shown in Table 1042.

  These sequences are known proteins called anti-leukoproteinase 1 precursor (SwissProt accession identifier ALK1_HUMAN, synonyms ALP, HUSI-1, sperm proteinase inhibitors, known proteins previously known herein) It is a variant of secretory leukocyte proteinase inhibitor, BLPI, mucus proteinase inhibitor, MPI, also known as WAP4 disulfide core domain protein 4, proteinase inhibitor WAP4) (SEQ ID NO: 1454).

  The protein anti-leukoproteinase 1 precursor is known or considered to have the following functions: Acid stable proteinases with strong affinity for trypsin, chymotrypsin, elastase and cathepsin G Inhibitor. It may prevent elastase-mediated damage to the oral cavity and possibly other mucosal tissues. The sequence of the protein anti-leukoproteinase 1 precursor is shown at the end of the application as "anti-leukoproteinase 1 precursor amino acid sequence". Localization of the protein anti-leukoproteinase 1 precursor is considered secretion.

  Clinical / therapeutic applications in humans (e.g. as targets for antibodies or small molecules and / or as direct therapy) are being investigated and available information related to these investigations is: Potential pharmaceutically relevant or therapeutically relevant activities of previously known proteins are: elastase inhibitors, tryptase inhibitors. The therapeutic role of proteins displayed by clusters is expected. Information is present in drug databases or public databases (eg, above) that may or may not be used to apply this protein or portions thereof for potential treatment (anti-inflammatory, anti-asthmatic) So we assigned a cluster to this area.

  The following GO annotation applies to previously known proteins. The following annotations were found: protease inhibitors, serine protease inhibitors that are annotations related to molecular function.

  GO assignments can be made at one or more http: // www. expasy. SwissProt / TremBl Protein knowledgebase available from ch / sprot / or http: // www. ncbi. nlm. nih. Depends on Locuslink available from gov / projects / LocusLink /.

  Cluster Z25299 can be used as a diagnostic marker by overexpression of transcripts of this cluster in cancer. The expression of such transcripts in normal tissues is also shown by the method previously described. The terms “number” in the right column of the table and the numbers on the y-axis of FIG. 35 refer to the weighted expression of ESTs in each category as “ppm” (the ppm of ESTs of a particular cluster in this category by ppm Ratio of expression to expression of all ESTs).

  In general, as shown for the histograms in FIG. 35 and Table 1043, the following results were obtained. This cluster was overexpressed (at least at minimal levels) in the following pathological conditions: malignant brain tumors, a mixture of malignant tumors from different tissues, and overexpression in ovarian cancer.

  As mentioned above, cluster Z25299 is characterized by the five transcripts listed in Table 1 above. These transcripts encode a protein that is a mutated form of the protein anti-leukoproteinase 1 precursor. A description of each mutein of the invention is provided herein.

  The mutein Z25299_PEA_2_P2 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript Z25299_PEA_2_T1. An alignment to a known protein (anti-leukoproteinase 1 precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between Z25299_PEA_2_P2 and ALK1_HUMAN 1. Corresponding to amino acids 1-131 of ALK1_HUMAN, first amino acid sequence at least 90% homologous to the corresponding MKSSGLFPFLVLLALGTLAPWAVEGSGKSFKAGVCPPKKSAQCLRYKKPECQSDWQCPGKKRCCPDTCGIKCLDPVDTPNPTRRKPGKCPVTYGQCLMLNPPNFCEMDGQCKRDLKCCMGMCGKSCVSPVK to amino acids 1-131 of Z25299_PEA_2_P2, the polypeptide having a sequence corresponding to GKQGMRAH to amino acid 132-139 of Z25299_PEA_2_P2 At least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% phase Such second comprises the amino acid sequence, wherein the first and second amino acid distribution is contiguous, and in sequential order, the isolated chimeric polypeptide coding Z25299_PEA_2_P2.

  2. Z25299_PEA_2_P2 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence GKQGMRAH in Z25299_PEA_2_P2 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein Z25299_PEA_2_P2 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, enumerating other amino acids, and the last column shows SNPs as shown in Table 1045) It indicates whether it is known and the presence of a known SNP in the mutant protein Z25299_PEA_2_P2 sequence supports the deduced sequence of this mutant protein of the invention).

  The mutein, Z25299_PEA_2_P2, is encoded by the following transcript: Z25299_PEA_2_T1 (sequences shown at the end of the application). The code portion of the transcript Z25299_PEA_2_T1 is shown in bold, starting from position 124 and ending at position 540. The transcript also has the following SNPs listed in Table 1046 (showing its position on the nucleotide sequence, listing another nucleic acid, the last column shows whether the SNP is known, mutein Z25299_PEA_2_P2 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein Z25299_PEA_2_P3 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript Z25299_PEA_2_T2. An alignment to a known protein (anti-leukoproteinase 1 precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report on comparison between Z25299_PEA_2_P3 and ALK1_HUMAN 1. Corresponding to amino acids 1-131 of ALK1_HUMAN, first amino acid sequence at least 90% homologous to the corresponding MKSSGLFPFLVLLALGTLAPWAVEGSGKSFKAGVCPPKKSAQCLRYKKPECQSDWQCPGKKRCCPDTCGIKCLDPVDTPNPTRRKPGKCPVTYGQCLMLNPPNFCEMDGQCKRDLKCCMGMCGKSCVSPVK to amino acids 1-131 of Z25299_PEA_2_P3, the polypeptide having a sequence corresponding to GEKRHHKQLRDQEVDPLEMRRHSAG to amino acid 132-156 of Z25299_PEA_2_P3 At least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% Most preferably comprises at least 95% homologous to a second amino acid sequence, wherein the first and second amino acid distribution is contiguous, and in sequential order, the isolated chimeric polypeptide coding Z25299_PEA_2_P3.

  2. Z25299_PEA_2_P3 comprising a polypeptide at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence GEKRHHKQLRDQEVDPLRHRHSAG in Z25299_PEA_2_P3 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein Z25299_PEA_2_P3 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows SNPs as shown in Table 1047) It indicates whether it is known and the presence of a known SNP in the mutant protein Z25299_PEA_2_P3 sequence supports the deduced sequence of this mutant protein of the invention).

  The mutein, Z25299_PEA_2_P3, is encoded by the following transcript: Z25299_PEA_2_T2 (sequences shown at the end of the application). The coding part of the transcript Z25299_PEA_2_T2 is shown in bold, starting from position 124 and ending at position 591. The transcript also has the following SNPs listed in Table 1048 (showing its position on the nucleotide sequence and listing another nucleic acid, the last column shows whether the SNP is known, mutein Z25299_PEA_2_P3 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein Z25299_PEA_2_P7 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript Z25299_PEA_2_T6. An alignment to a known protein (anti-leukoproteinase 1 precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between Z25299_PEA_2_P7 and ALK1_HUMAN 1. MKSSGLFPFLLVL GLTLAWEAVESGSGKSF KG FSK AGQKKQCQDQQCPGKKRICCDPVDCTPNPN corresponding to amino acids 1 to 81 of ALK1_HUMAN and corresponding to amino acids 1 to 81 of Z25299_PEA_2_P7, a first amino acid sequence at least 90% homologous to ZCD299, Said first and second amino acids comprising a second amino acid sequence which is at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous The arrangement is in adjacent and sequential order, Z 2529 Isolated chimeric polypeptide encoding _PEA_2_P7.

  2. Z25299_PEA_2_P7 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence RGSLGSAQ in Z25299_PEA_2_P7 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein Z25299_PEA_2_P7 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows SNPs as shown in Table 1049) It indicates whether it is known and the presence of a known SNP in the mutant protein Z25299_PEA_2_P7 sequence supports the deduced sequence of this mutant protein according to the invention).

  The mutein, Z25299_PEA_2_P7, is encoded by the following transcript: Z25299_PEA_2_T6 (sequences shown at the end of the application). The coding part of the transcript Z25299_PEA_2_T6 is shown in bold, starting from position 124 and ending at position 390. The transcript also has the following SNPs listed in Table 1050 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein Z25299_PEA_2_P7 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein Z25299_PEA_2_P10 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript Z25299_PEA_2_T9. An alignment to a known protein (anti-leukoproteinase 1 precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between Z25299_PEA_2_P10 and ALK1_HUMAN 1. MKSSGLFPFLLVL GLT AVE WPGEGGS GKS FK FAG CPPKSAQCLRYKKPEC QSDWQCPGKKLYCLDPV TGPNT corresponding to amino acids 1-82 of ALK1_HUMAN and corresponding to amino acids 1-82 of Z25299_PEA_2P10, comprising a first amino acid sequence at least 90% homologous to the Z25299_PE14_P14

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein Z25299_PEA_2_P10 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows SNPs as shown in Table 1051) It indicates whether it is known and the presence of a known SNP in the mutant protein Z25299_PEA_2_P10 sequence supports the deduced sequence of this mutant protein according to the invention).

  The mutein, Z25299_PEA_2_P10, is encoded by the following transcript: Z25299_PEA_2_T9 (sequences shown at the end of the application). The code portion of the transcript Z25299_PEA_2_T9 is shown in bold, starting from position 124 and ending at position 369. The transcript also has the following SNPs listed in Table 1052 (showing its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein Z25299_PEA_2_P10 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  As mentioned above, cluster Z25299 is characterized by the eleven segments listed in Table 2 above, the sequence of which is shown at the end of the application. These segments are part of the nucleic acid sequence, which are of particular interest and are individually described herein. A description of each segment of the invention is provided herein.

  The segment cluster Z25299_PEA_2_node_20 of the present invention is supported by six libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: Z25299_PEA_2_T1. Table 1053 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z25299_PEA_2_node_21 of the present invention is supported by 162 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: Z25299_PEA_2_T1, Z25299_PEA_2_T6, and Z25299_PEA_2_T9. Table 1054 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z25299_PEA_2_node_23 of the present invention is supported by two libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: Z25299_PEA_2_T2. Table 1055 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z25299_PEA_2_node_24 of the present invention is supported by two libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: Z25299_PEA_2_T2 and Z25299_PEA_2_T3. Table 1056 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z25299_PEA_2_node_8 of the present invention is supported by 218 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: Z25299_PEA_2_T1, Z25299_PEA_2_T2, Z25299_PEA_2_T3, Z25299_PEA_2_T6, and Z25299_PEA_2_T9. Table 1057 below describes the start and end positions of this segment on each transcript.

  According to an optional embodiment of the present invention, there is also provided a short segment associated with the above cluster. These segments are up to about 120 bp in length and are therefore included in the individual descriptions.

  The segment cluster Z25299_PEA_2_node_12 of the present invention is supported by 228 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: Z25299_PEA_2_T1, Z25299_PEA_2_T2, Z25299_PEA_2_T3, Z25299_PEA_2_T6, and Z25299_PEA_2_T9. Table 1058 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z25299_PEA_2_node_13 of the present invention is supported by 246 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: Z25299_PEA_2_T1, Z25299_PEA_2_T2, Z25299_PEA_2_T3, Z25299_PEA_2_T6, and Z25299_PEA_2_T9. Table 1059 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z25299_PEA_2_node_14 according to the invention can be found in the following transcripts: Z25299_PEA_2_T1, Z25299_PEA_2_T2, Z25299_PEA_2_T3, Z25299_PEA_2_T6, and Z25299_PEA_2_T9. Table 1060 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z25299_PEA_2_node_17 according to the invention can be found in the following transcript: Z25299_PEA_2_T1, Z25299_PEA_2_T2, and Z25299_PEA_2_T3. Table 1061 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z25299_PEA_2_node_18 of the present invention is supported by 221 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: Z25299_PEA_2_T1, Z25299_PEA_2_T2, Z25299_PEA_2_T3, and Z25299_PEA_2_T6. Table 1062 below describes the start and end positions of this segment on each transcript.

  The segment cluster Z25299_PEA_2_node_19 of the present invention is supported by 197 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: Z25299_PEA_2_T1, Z25299_PEA_2_T2, Z25299_PEA_2_T3, and Z25299_PEA_2_T6. Table 1063 below describes the start and end positions of this segment on each transcript.

Mutated protein alignment against previously known proteins:
Sequence name: / tmp / oXgeQ4MeyL / K6Vqb1MQu2: ALK1_HUMAN

Sequence documentation:

Alignment of: Z25299_PEA_2_P2 x ALK1_HUMAN ..

Alignment segment 1/1:

Quality: 1371.00 Escore: 0
Matching length: 131 Total length: 131
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MKSSGLFPFLVLLALGTLAPWAVEGGSGKSKSFKAGVCPPKKSAQCLRYKKPE 50
||||||||||||||||||||||||||||||||||||||||
1 MKSSGLFPFLVLLALGTLAPWAVEGGSGKSKSFKAGVCPPKKSAQCLRYKKPE 50
....
51 CQSDWQCPGKKRCCPDTCGIKDLCDPVDTPNPTRKPGKCPVTYGQCLMLN 100
||||||||||||||||||||||||||||||||||||||||
51 CQSDWQCPGKKRCCPDTCGIKDLCDPVDTPNPTRKPGKCPVTYGQCLMLN 100
....
101 PNFFCEMDGQCKRDLKCCMGMCG CVSPVK 131
|||||||||||||||||||||||||||||
101 PNFFCEMDGQCKRDLKCCMGMCG CVSPVK 131






Sequence name: / tmp / rbf314VLIm / yR43i4SbP4: ALK1_HUMAN

Sequence documentation:

Alignment of: Z25299_PEA_2_P3 x ALK1_HUMAN ..

Alignment segment 1/1:

Quality: 1371.00 Escore: 0
Matching length: 131 Total length: 131
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MKSSGLFPFLVLLALGTLAPWAVEGGSGKSKSFKAGVCPPKKSAQCLRYKKPE 50
||||||||||||||||||||||||||||||||||||||||
1 MKSSGLFPFLVLLALGTLAPWAVEGGSGKSKSFKAGVCPPKKSAQCLRYKKPE 50
....
51 CQSDWQCPGKKRCCPDTCGIKDLCDPVDTPNPTRKPGKCPVTYGQCLMLN 100
||||||||||||||||||||||||||||||||||||||||
51 CQSDWQCPGKKRCCPDTCGIKDLCDPVDTPNPTRKPGKCPVTYGQCLMLN 100
....
101 PNFFCEMDGQCKRDLKCCMGMCG CVSPVK 131
|||||||||||||||||||||||||||||
101 PNFFCEMDGQCKRDLKCCMGMCG CVSPVK 131






Sequence name: / tmp / KCtSXACZXe / rK4T6LKeRX: ALK1_HUMAN

Sequence documentation:

Alignment of: Z25299_PEA_2_P7 x ALK1_HUMAN ..

Alignment segment 1/1:

Quality: 835.00 Escore: 0
Matching length: 81 Total length: 81
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MKSSGLFPFLVLLALGTLAPWAVEGGSGKSKSFKAGVCPPKKSAQCLRYKKPE 50
||||||||||||||||||||||||||||||||||||||||
1 MKSSGLFPFLVLLALGTLAPWAVEGGSGKSKSFKAGVCPPKKSAQCLRYKKPE 50
....
51 CQSDWQCPGKKRCCPDTCGIKCLPDVDTNPN 81
|||||||||||||||||||||||||||||
51 CQSDWQCPGKKRCCPDTCGIKCLPDVDTNPN 81






Sequence name: / tmp / LcBlcAxB6c / NSI9pqfxoU: ALK1_HUMAN

Sequence documentation:

Alignment of: Z25299_PEA_2_P10 x ALK1_HUMAN ..

Alignment segment 1/1:

Quality: 844.00 Escore: 0
Matching length: 82 Total length: 82
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MKSSGLFPFLVLLALGTLAPWAVEGGSGKSKSFKAGVCPPKKSAQCLRYKKPE 50
||||||||||||||||||||||||||||||||||||||||
1 MKSSGLFPFLVLLALGTLAPWAVEGGSGKSKSFKAGVCPPKKSAQCLRYKKPE 50
....
51 CQSDWQCPGKKRCCPDTCGIKCLPDVDTNPPT 82
||||||||||||||||||||||||||||||
51 CQSDWQCPGKKRCCPDTCGIKCLPDVDTNPPT 82

Expression of the acid-stable protease inhibitor Z25299 transcript, which is a secreted leukocyte protease inhibitor detectable by an amplicon as shown in the sequence name Z25299junc13-14-21 in normal and cancerous lung tissue Junc13-14-21, Z25299junc13-14-4 21 amplicons (SEQ ID NO: 1666) and acid stable protease inhibitor transcripts that are secretory leukocyte protease inhibitors detectable by the primers Z25299 junc 13-14-21 F (SEQ ID NO: 1664) and Z 25 299 junc 13-14-21 R (SEQ ID NO: 1665) Expression was measured by real time PCR. In parallel, four housekeeping genes-PBGD (GenBank Accession No. BC019323, Amplicon – PBGD-Amplicon, SEQ ID No. 334), HPRT1 (GenBank Accession No. NM_000194, Amplicon – HPRT1- Amplicons, SEQ ID NO: 1297), Ubiquitin (GenBank Accession No. BC000449, Amplicon – Ubiquitin-Amplicon SEQ ID NO: 328), and SDHA (GenBank Accession No. NM_004168, Amplicon – SDHA-Amplicon The expression of SEQ ID NO: 331) was similarly measured. For each RT sample, the expression of the amplicon was normalized to the geometric mean of the housekeeping gene dose. The normalized amount of each RT sample is the center of the amount of normal postmortem (PM) samples (sample numbers 47-50, 90-93, 96-99 above, Table 2, "tissue samples in the test panel") Divided by a value, the fold expression of each sample's differential expression to the median of normal PM samples was obtained.

  FIG. 36 is a histogram showing downregulation of the secreted leukocyte protease inhibitor acid stable protease inhibitor transcript in several cancerous lung samples compared to normal samples.

  As apparent from FIG. 36, the expression of the acid stable protease inhibitor transcript which is a secretory leukocyte protease inhibitor detectable by the above amplicon in a cancer sample is a non-cancerous sample (sample numbers 47 to 50, 90- 93, 96-99, Table 2, "Tissue samples in test panel" were significantly lower.

  Statistical analysis was applied to verify the significance of these results, as described below.

  The P value for the difference in expression levels of acid stable protease inhibitor transcripts that are detectable by the above amplicon in lung cancer samples versus normal tissue samples is determined by T-test to be 1.98E-04 did. This value indicates that the result is statistically significant.

  Primer pairs are also optionally and preferably included within the scope of the present invention, for example, in the above experiments the following primers were used only as a non-limiting illustration of suitable primer pairs: Z25299junc13-14-21F forward direction Primer and Z25299 junc 13-14-21 R reverse primer.

  The present invention also preferably includes any amplicon obtained by use of any suitable primer pair (e.g. in the above experiments) and obtained the following amplicons only as a non-limiting illustration of a suitable amplicon : Z 25 299 junc 13-14-21.

Forward primer (SEQ ID NO: 1664): ACCCCAAACCCAACTTGATTC
Reverse primer (SEQ ID NO: 1665): TCAGTGGTGGAGCCAAAGTCTC
Amplicon (SEQ ID NO: 1666): ACCCC AAACCCA ACT TG AT CCTGCCATATGGAGGAGGCTCTGGAGTCCTGCTCTGTGTGTCCAGGTCCTCTTC ACCCTGAGACTTGGCTCCACTACTGA

Z25299 transcripts detectable by the amplicon shown in the sequence name Z25299seg20 in normal and cancerous lung tissue detectable by the primers seg20, Z25299seg20 amplicon (SEQ ID NO: 1669) and Z25299seg20F (SEQ ID NO: 1667) and Z25299seg20R (SEQ ID NO: 1668) The expression of acid stable protease inhibitor transcript, which is a secretory leukocyte protease inhibitor, was measured by real time PCR. In parallel, four housekeeping genes-PBGD (GenBank Accession No. BC019323, Amplicon – PBGD-Amplicon, SEQ ID No. 334), HPRT1 (GenBank Accession No. NM_000194, Amplicon – HPRT1- Amplicons, SEQ ID NO: 1297), Ubiquitin (GenBank Accession No. BC000449, Amplicon – Ubiquitin-Amplicon SEQ ID NO: 328), and SDHA (GenBank Accession No. NM_004168, Amplicon – SDHA-Amplicon The expression of SEQ ID NO: 331) was similarly measured. For each RT sample, the expression of the amplicon was normalized to the geometric mean of the housekeeping gene dose. The normalized amount of each RT sample is the center of the amount of normal postmortem (PM) samples (sample numbers 47-50, 90-93, 96-99 above, Table 2, "tissue samples in the test panel") Divided by the value. The reciprocal of this ratio was then calculated to obtain the downregulation of each sample relative to the median of normal PM samples.

  FIG. 37 is a histogram showing downregulation of the secreted leukocyte protease inhibitor acid stable protease inhibitor transcript in several cancerous lung samples compared to normal samples. The number and proportion of samples showing downregulation of at least 5 times of the total number of test samples are shown below.

  As apparent from FIG. 37, the expression of the acid stable protease inhibitor transcript which is a secretory leukocyte protease inhibitor detectable by the above amplicon in a cancer sample is a non-cancerous sample (sample numbers 47-50, 90- 93, 96-99, Table 2, "Tissue samples in test panel" were significantly lower. Obviously, 6 out of 15 adenocarcinoma samples, 9 out of 16 squamous cell carcinoma samples, 3 out of 4 large cell carcinoma samples, 8 small cell carcinoma samples At least 5 fold downregulation was found with 8 of the

  Statistical analysis was applied to verify the significance of these results as described below.

  P-values for differences in expression levels of acid stable protease inhibitor transcripts that are detectable by the above amplicon in lung cancer samples versus normal tissue samples are determined by T-test, 9.43 E— for adenocarcinomas. 02, 5.62E-02 for squamous cell carcinoma, 3.38E-01 for large cell carcinoma, and 3.78E-02 for small cell carcinoma.

  The 5-fold downregulation threshold was found to be different between cancer and normal samples, checked by Fisher's exact test, P value is 3.73E-02 for adenocarcinoma, squamous cell carcinoma in adenocarcinoma 1.10E-02, 2.64E-02 for large cell carcinoma and 7.14E-05 for small cell carcinoma. The above values indicate that the results are statistically significant.

  Primer pairs are also optionally and preferably included within the scope of the present invention, for example, in the above experiments the following primers were used only as non-limiting examples of suitable primer pairs: Z25299seg20F forward primer and Z25299seg20R reverse Direction primer.

  The present invention also preferably includes any amplicon obtained by use of any suitable primer pair (e.g. in the above experiments) and obtained the following amplicons only as a non-limiting illustration of a suitable amplicon : Z 25 299 seg 20.

Forward primer (SEQ ID NO: 1667): CTCCTGAACCCTACTCCAAGCCA
Reverse primer (SEQ ID NO: 1668): CAGGCGATCCTATGGAAATCC
Amplicon (SEQ ID NO: 1669): CTCCTGAACCCTACTCCAAGCACAGCCTCTGTCTGACTCCTTTGTCCTTCAAGAGAACTGTTCTCCAGGTCCTCAGGGCCAGGATTTCCATAGGATCGCCTGG

Expression of homo-Sapiens secreting leukocyte protease inhibitor (anti-leukoproteinase) (SLPI) Z25299 transcript detectable by an amplicon as shown in sequence name Z25299 seg23 in normal and cancerous lung tissue seg23, Z25 299 seg23 amplicon (SEQ ID NO: 1672) The expression of homo-Sapiens secreting leukocyte protease inhibitor (anti-leukoproteinase) (SLPI) transcripts detectable by the primers Z25299seg23F (SEQ ID NO: 1670) and Z25299seg23R (SEQ ID NO: 1671) was measured by real-time PCR. In parallel, four housekeeping genes-PBGD (GenBank Accession No. BC019323, Amplicon – PBGD-Amplicon, SEQ ID No. 334), HPRT1 (GenBank Accession No. NM_000194, Amplicon – HPRT1- Amplicons, SEQ ID NO: 1297), Ubiquitin (GenBank Accession No. BC000449, Amplicon – Ubiquitin-Amplicon SEQ ID NO: 328), and SDHA (GenBank Accession No. NM_004168, Amplicon – SDHA-Amplicon The expression of SEQ ID NO: 331) was similarly measured. For each RT sample, the expression of the amplicon was normalized to the geometric mean of the housekeeping gene dose. The normalized amount of each RT sample was divided by the median of the amounts of normal postmortem (PM) samples (sample numbers 47-50, 90-93, 96-99 above, Table 2 above). The reciprocal of this ratio was then calculated to obtain the downregulation of each sample relative to the median of normal PM samples.

  FIG. 68 is a histogram showing downregulation of the homo-Sapiens secreting leukocyte protease inhibitor (anti-leukoproteinase) (SLPI) transcript in cancerous lung samples as compared to normal samples.

  As is apparent from FIG. 68, expression of the homo-Sapiens secreting leukocyte protease inhibitor (anti-leukoproteinase) (SLPI) transcript detectable by the above amplicon in the cancer sample was determined by the non-cancerous sample (Sample No. 46). 50, 90-93, 96-99, significantly lower than Table 2). Obviously, 7 out of 15 adenocarcinoma samples, 9 out of 16 squamous cell carcinoma samples, 3 out of 4 large cell carcinoma samples, 8 small cell carcinoma samples At least 10 fold downregulation was found with 8 of the

  Primer pairs are also optionally and preferably included within the scope of the present invention, for example, in the above experiments the following primers were used only as non-limiting examples of suitable primer pairs: Z25299seg23F forward primer and Z25299seg23R reverse Direction primer.

  The present invention also preferably includes any amplicon obtained by use of any suitable primer pair (e.g. in the above experiments) and obtained the following amplicons only as a non-limiting illustration of a suitable amplicon : Z 25 299 seg 23.

Primer:
Forward primer Z25299seg23F (SEQ ID NO: 1670): CAAGCAATTGAGGGACCAGG
Reverse primer Z25299seg23R (SEQ ID NO: 1671): CAAAAAACATTGTTAATGAGAGAGAGATGAC
Amplicon Z 25 299 seg 23 F (SEQ ID NO: 1672): CAAGCAATTGAGGGACCGAGATGGGATCCTC TAGAGATGAGGAGGGCATTCTGCTGGATGACTTTTAAAAATGTTTCTCCAGAGTCATCTCTCTCATTAACAATGTTTTTTG

Expression of the acid stable proteinase inhibitor Z25299 transcript which is a secretory leukocyte protease inhibitor detectable by an amplicon as shown in sequence name Z25299seg20 in different normal tissues Z25299seg20 amplicon (SEQ ID NO: 1669) and primer Z25299seg23F (SEQ ID NO: 1667) and The expression of secretory leukocyte protease inhibitor transcripts detectable by Z25299seg20R (SEQ ID NO: 1668) was measured by real time PCR. In parallel, four housekeeping genes-RPL19 (GenBank Accession No. NM_000981, RPL19 amplicon, SEQ ID No. 1630), TATA box (GenBank Accession No. NM_003194, TATA amplicon, SEQ ID No. 1633), ubiquitin (GenBank Accession No. The expression of BC000449, amplicon – ubiquitin-amplicon, SEQ ID NO: 328), and SDHA (GenBank Accession No. NM_004168, amplicon – SDHA-amplicon, SEQ ID NO: 331) was similarly measured. For each RT sample, the expression of the amplicon was normalized to the geometric mean of the housekeeping gene dose. The normalized amount of each RT sample was divided by the median of the amounts of ovary samples (Sample Nos. 18-20, Table 3) to obtain the relative expression value of each sample relative to the median of the ovary samples.

Primer:
Forward primer (SEQ ID NO: 1667): CTCCTGAACCCTACTCCAAGCCA
Reverse primer (SEQ ID NO: 1668): CAGGCGATCCTATGGAAATCC
Amplicon (SEQ ID NO: 1669): CTCCTGAACCCTACTCCAAGCACAGCCTCTGTCTGACTCCTTTGTCCTTCAAGAGAACTGTTCTCCAGGTCCTCAGGGCCAGGATTTCCATAGGATCGCCTGG

  The results are shown in FIG. 69, which shows the expression of the acid stable proteinase inhibitor Z25299 transcript which is a secreted leukocyte protease inhibitor detectable by the amplicon shown in the sequence name Z25299seg20 in different normal tissues.

Expression of the detectable secretory leukocyte protease inhibitor Z25299 transcript by the amplicon shown in the sequence name Z25299seg23 in different normal tissues Z25299seg23 amplicon (SEQ ID NO: 1672) and by primers Z25299seg23F (SEQ ID NO: 1670) and Z25299seg23R (SEQ ID NO: 1671) The expression of detectable secretory leukocyte protease inhibitor transcripts was measured by real time PCR. In parallel, four housekeeping genes-RPL19 (GenBank Accession No. NM_000981, RPL19 amplicon, SEQ ID No. 1630), TATA box (GenBank Accession No. NM_003194, TATA amplicon, SEQ ID No. 1633), ubiquitin (GenBank Accession No. The expression of BC000449, amplicon – ubiquitin-amplicon, SEQ ID NO: 328), and SDHA (GenBank Accession No. NM_004168, amplicon – SDHA-amplicon, SEQ ID NO: 331) was similarly measured. For each RT sample, the expression of the amplicon was normalized to the geometric mean of the housekeeping gene dose. The normalized amount of each RT sample was divided by the median of the amounts of ovary samples (Sample Nos. 18-20, Table 3) to obtain the relative expression value of each sample relative to the median of the ovary samples.

Primer:
Forward primer Z25299seg23F (SEQ ID NO: 1670): CAAGCAATTGAGGGACCAGG
Reverse primer Z25299seg23R (SEQ ID NO: 1671): CAAAAAACATTGTTAATGAGAGAGAGATGAC
Amplicon Z 25 299 seg 23 F (SEQ ID NO: 1672): CAAGCAATTGAGGGACCGAGATGGGATCCTC TAGAGATGAGGAGGGCATTCTGCTGGATGACTTTTAAAAATGTTTCTCCAGAGTCATCTCTCTCATTAACAATGTTTTTTG

  The results are shown in FIG. 70, which shows the expression of the acid stable proteinase inhibitor Z25299 transcript which is a secreted leukocyte protease inhibitor detectable by the amplicon shown in the sequence name Z25299seg23 in different normal tissues.

Description of cluster HSSTROL3 The cluster HSSTROL3 is characterized by 6 transcripts and 16 segments of interest, the names of which are given in tables 1064 and 1065 respectively, and the sequence itself is given at the end of the application. Selected protein variants are shown in Table 1066.

  These sequences are stromelysin-3 precursors (SwissProt accession identifier MM11_HUMAN, synonym EC3.4.24.-, matrix metalloproteinase-11, which is a known protein, previously known herein as a protein). It is a variant of (also known as MMP-11, ST3, SL-3) (SEQ ID NO: 1455).

  The protein stromelysin-3 precursor is known or considered to have the following functions: It may play an important role in the progression of epithelial malignancies. The sequence of the protein stromelysin-3 precursor is shown at the end of the application as "stromelysin-3 precursor amino acid sequence".

  The following GO annotation applies to previously known proteins. The following annotations were found: annotations related to biological processes: proteolysis and peptide degradation, developmental processes, morphogenesis, annotations related to molecular function: stromelysin 3, calcium binding, zinc binding , Hydrolases, as well as extracellular substrates that are annotations related to cellular components.

  GO assignments can be made at one or more http: // www. expasy. SwissProt / TremBl Protein knowledgebase available from ch / sprot / or http: // www. ncbi. nlm. nih. Depends on Locuslink available from gov / projects / LocusLink /.

  Cluster HSSTROL3 can be used as a diagnostic marker by overexpression of transcripts of this cluster in cancer. The expression of such transcripts in normal tissues is also shown by the method previously described. The terms “number” in the left column of the table and the numbers on the y-axis of FIG. 38 refer to the weighted expression of ESTs in each category as “ppm” (the ppm of ESTs of a particular cluster in this category by ppm) Ratio of expression to expression of all ESTs).

  In general, as shown for the histograms in FIG. 38 and Table 1067, the following results were obtained. This cluster was overexpressed (at least at minimal levels) in the following pathological conditions: transitional cell carcinoma, epithelial malignancy, a mixture of malignancies from different tissues, and pancreatic cancer.

  As mentioned above, cluster HSSTROL3 is characterized by the six transcripts listed in Table 1 above. These transcripts encode proteins which are variants of the protein stromelysin-3 precursor. A description of each mutein of the invention is provided herein.

  The mutein HSSTROL3_P4 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript HSSTROL3_T5. An alignment to a known protein (stromelysin-3 precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of the comparison between HSSTROL3_P4 and MM11_HUMAN 1. JLPH JH JILs, and is a corresponding UH JIV J III NIV J III JV J III J 7 J 7 J7 J 7 J7 J7 J7 J7 Jc This is: JELs; GDDLPF corresponding to 445 and corresponding to amino acids 165 to 445 of HSSTROL3_P4 And at least 90% homologous second amino acid sequence JipijijiaierueieichieiefuefuPikeitieichiaruijidibuieichiefudiwaidiitidaburyutiaijididikyujitidieruerukyubuieieieichiiefujieichibuierujierukyueichititieieikeieieruemuesueiefuwaitiefuaruwaiPieruesueruesuPididishiarujibuikyueichieruwaijikyuPidaburyuPitibuitiesuarutiPieieruJipikyueijiaiditienuiaieiPieruiPidieiPiPidieishiieiesuefudieibuiesutiaiarujiieruefuefuefukeieijiefubuidaburyuarueruarujijikyuerukyuPijiwaiPieierueiesuarueichidaburyukyujieruPiesupibuidieieiefuidieikyujieichiaidaburyuefuefukyujieikyuwaidaburyubuiwaidijiikeiPibuieruJipiEipierutiierujierubuiaruefuPibuieichieieierubuidaburyuJipiikeienukeiaiwaiefuefuarujiarudiwaidaburyuaruefueichiPiesutiaruarubuidiesuPVPRRATDWRGVPSEIDAAFQDADG, sequence ALGVR corresponding to amino acids 446-496 of HSSTROL3_P4 A polypeptide having at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95%, of a third amino acid sequence homologous to the polypeptide having LVGGGHSSRFSHLVLVAGLPHACHRKSGSS SQVCLPEPSALLSVAG; An isolated chimeric polypeptide encoding HSSTROL3_P4, wherein the amino acid sequence of 1, the bridging amino acid, the second amino acid sequence, and the third amino acid sequence are adjacent and in sequential order.

  2. HSSTROL3_P4 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence ALGVRQLVGGGHSSRFSHLVGALPGHACHRKSGSSSQVCLPEPSALLSVAG in HSSTROL3_P4 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein HSSTROL3_P4 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows SNPs as shown in Table 1069) It is indicated whether it is known and the presence of a known SNP in the mutant protein HSSTROL3_P4 sequence supports the deduced sequence of this mutant protein according to the invention).

  The mutein, HSSTROL3_P4, is encoded by the following transcript: HSSTROL3_T5 (sequences shown at the end of the application). The coding portion of the transcript HSSTROL3_T5 is shown in bold, starting from position 24 and ending at position 1511. The transcript also has the following SNPs listed in Table 1070 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, the mutein HSSTROL3_P4 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein HSSTROL3_P5 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcripts HSSTROL3_T8 and HSSTROL3_T9. An alignment to a known protein (stromelysin-3 precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of the comparison between HSSTROL3_P5 and MM11_HUMAN 1. JLPH JH JILs, and is a corresponding UH JIV J III JIV J III NIV J III JV J III JV J III JV J III JIV J 7 NvH Jl Jl s. GDDLFF corresponding to 358 and corresponding to amino acids 165 to 358 of HSSTROL3_P5 And at least 90% homologous second amino acid sequence JipijijiaierueieichieiefuefuPikeitieichiaruijidibuieichiefudiwaidiitidaburyutiaijididikyujitidieruerukyubuieieieichiiefujieichibuierujierukyueichititieieikeieieruemuesueiefuwaitiefuaruwaiPieruesueruesuPididishiarujibuikyueichieruwaijikyuPidaburyuPitibuitiesuarutiPieieruJipikyueijiaiditienuiaieiPieruiPidieiPiPidieishiieiesuefudieibuiesutiaiarujiieruefuefuefukeieijiefubuidaburyuarueruarujijikyuerukyuPijiwaiPieierueiesuRHWQGLPSPVDAAFEDAQGHIWFFQ, polypeptide at least 70% with a sequence corresponding to ELGFPSSTGRDESLEHCRCQGLHK to amino acid 359-382 of HSSTROL3_P5, optionally at least 80%, preferably at least 85%, more Preferably at least 90%, most preferred Or a third amino acid sequence that is at least 95% homologous, wherein the first amino acid sequence, the bridging amino acid, the second amino acid sequence, and the third amino acid sequence are adjacent and in a consecutive order, An isolated chimeric polypeptide encoding HSSTROL3_P5.

  2. HSSTROL3_P5 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence ELGFPSSTGRDESLEHCRCQGLHK in HSSTROL3_P5 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein HSSTROL3_P5 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows SNPs as shown in Table 1071) It is shown whether it is known and the presence of a known SNP in the mutant protein HSSTROL3_P5 sequence supports the deduced sequence of this mutant protein according to the invention).

  The mutein, HSSTROL3_P5, is encoded by the following transcript: HSSTROL3_T8 and HSSTROL3_T9 (sequences shown at the end of the application).

  The coding portion of the transcript HSSTROL3_T8 is shown in bold, starting from position 24 and ending at position 1569. The transcript also has the following SNPs listed in Table 1072 (showing its position on the nucleotide sequence and listing another nucleic acid, the last column shows whether the SNP is known, the mutein HSSTROL3_P5 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The coding portion of the transcript HSSTROL3_T9 is shown in bold, starting from position 24 and ending at position 1169. The transcript also has the following SNPs listed in Table 1073 (showing its position on the nucleotide sequence and listing another nucleic acid, the last column shows if the SNP is known, the mutein HSSTROL3_P5 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein HSSTROL3_P7 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript HSSTROL3_T10. An alignment to a known protein (stromelysin-3 precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of the comparison between HSSTROL3_P7 and MM11_HUMAN 1. JLPH JH JILs, and is a corresponding UH JIV J III JIV J III J 7 J 7 J 7 J 7 J 7 J 7 J7Gvl 7 UoGl 7 UoG OoIl Jl. GDDLPF corresponding to 359 and corresponding to amino acids 165 to 359 of HSSTROL3_P7 And at least 90% homologous second amino acid sequence JipijijiaierueieichieiefuefuPikeitieichiaruijidibuieichiefudiwaidiitidaburyutiaijididikyujitidieruerukyubuieieieichiiefujieichibuierujierukyueichititieieikeieieruemuesueiefuwaitiefuaruwaiPieruesueruesuPididishiarujibuikyueichieruwaijikyuPidaburyuPitibuitiesuarutiPieieruJipikyueijiaiditienuiaieiPieruiPidieiPiPidieishiieiesuefudieibuiesutiaiarujiieruefuefuefukeieijiefubuidaburyuarueruarujijikyuerukyuPijiwaiPieierueiesuaruHWQGLPSPVDAAFEDAQGHIWFFQG, polypeptide at least 70% with a sequence corresponding to TTGVSTPAPGV to amino acid 360-370 of HSSTROL3_P7, optionally at least 80%, preferably at least 85%, more Preferably at least 90%, most preferably at least 95% A single HSSTROL3_P7 encoding sequence comprising the same third amino acid sequence, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence, and third amino acid sequence are adjacent and in sequential order. Detached chimeric polypeptide.

  2. HSSTROL3_P7 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence TTGVSTPAPGV in HSSTROL3_P7 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein HSSTROL3_P7 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows SNPs as shown in Table 1074) It is shown whether it is known and the presence of a known SNP in the mutant protein HSSTROL3_P7 sequence supports the deduced sequence of this mutant protein according to the invention).

  The mutein, HSSTROL3_P7, is encoded by the following transcript: HSSTROL3_T10 (sequences shown at the end of the application). The coding part of the transcript HSSTROL3_T10 is shown in bold, starting from position 24 and ending at position 1133. The transcript also has the following SNPs listed in Table 1075 (showing its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, the mutein HSSTROL3_P7 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein HSSTROL3_P8 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript HSSTROL3_T11. An alignment to a known protein (stromelysin-3 precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of the comparison between HSSTROL3_P8 and MM11_HUMAN 1. JLPH JH JILs, and is used as a N-HIV J III JIV J III N- while, and can also be used as a UH. GDDLPF corresponding to 286 286 and also corresponding to amino acids 165 to 286 of HSSTROL3_P8 GPGGILAHAFFPKTHREGDVHFDYDETIGDDQGTDLLQVAAHEFGHGLQHTTAAKALMSAFYTFRYPLSLDDCDRGVQHLYGQPWPTVTSRTPALGPQAGIDTNEIAPLE The second amino acid sequence corresponding to the amino acid 278 to 301 of HSSTROL3. Is at least 90%, most preferably at least 95% homologous with a third amino acid sequence, said first amino acid sequence, the bridging amino acid, the second amino acid sequence and the third amino acid sequence being adjacent and Continuously In order, the isolated chimeric polypeptide coding HSSTROL3_P8.

  2. HSSTROL3_P8 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 90%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence VRPCLPVPLLLCWPL in HSSTROL3_P8 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein HSSTROL3_P8 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows SNPs as shown in Table 1076) It is shown whether it is known and the presence of a known SNP in the mutant protein HSSTROL3_P8 sequence supports the deduced sequence of this mutant protein according to the invention).

  The mutein, HSSTROL3_P8, is encoded by the following transcript: HSSTROL3_T11 (sequences shown at the end of the application). The coding part of the transcript HSSTROL3_T11 is shown in bold, starting from position 24 and ending at position 926. The transcript also has the following SNPs listed in Table 1077 (showing its position on the nucleotide sequence and listing another nucleic acid, the last column shows whether the SNP is known, the mutein HSSTROL3_P8 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein HSSTROL3_P9 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript HSSTROL3_T12. An alignment to a known protein (stromelysin-3 precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of the comparison between HSSTROL3_P9 and MM11_HUMAN 1. A corresponding amino acid 1 to 96 of MM11_HUMAN and corresponding to amino acid 1 to 96 of HSSTROL3_P9 MAPAAWLRSAAARALLPPMLLLLLQPPOLARALPPDVHHLHAERRGPQPWHAALPSPSPAPAPATQ EAPRPASSLRPPRCGVPPDSGLSARNRQK The first amino acid sequence at least 90% homologous to the amino acids 11 to 11 and 11 to 17 And the corresponding second amino acid sequence at least 90% homologous to RILRFPWQLVQEQVRQTM AAELKVWSDVTPLTFTEVHEGRADIMIDARYW, the bridging amino acid H corresponding to amino acid 148 of HSSTROL3_P9, MM Corresponding to amino acids 165-359 of 1_HUMAN, the polypeptide having a GDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWTIGDDQGTDLLQVAAHEFGHVLGLQHTTAAKALMSAFYTFRYPLSLSPDDCRGVQHLYGQPWPTVTSRTPALGPQAGIDTNEIAPLEPDAPPDACEASFDAVSTIRGELFFFKAGFVWRLRGGQLQPGYPALASRHWQGLPSPVDAAFEDAQGHIWFFQG corresponding to amino acids 149-343 of HSSTROL3_P9 the third amino acid sequence at least 90% homologous, sequences corresponding to TTGVSTPAPGV to amino acid 344-354 of HSSTROL3_P9 And at least 70%, A fourth amino acid sequence which is optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous; said first amino acid sequence, said second amino acid sequence An isolated chimeric polypeptide encoding HSSTROL3_P9, wherein the bridging amino acid, the third amino acid sequence, and the fourth amino acid sequence are in contiguous and sequential order.

  2. Length “n” (wherein n is at least about 10 amino acids long, optionally at least about 20 amino acids long, preferably at least about 30 amino acids long, more preferably at least about 40 amino acids long, most preferably at least about 50 amino acids in length, at least two amino acids comprising KR, starting from any of the following structures: amino acid numbers 96-x to 96, amino acid numbers 97 + ((n-2) -x) (formula An isolated chimeric polypeptide encoding a rim portion of HSSTROL3_P9, comprising a polypeptide having a sequence terminating in: x) varying from 0 to n-2).

  3. HSSTROL3_P9 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence TTGVSTPAPGV in HSSTROL3_P9 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein HSSTROL3_P9 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows SNPs as shown in Table 1078) It is shown whether it is known and the presence of a known SNP in the mutant protein HSSTROL3_P9 sequence supports the deduced sequence of this mutant protein according to the invention).

  The mutein, HSSTROL3_P9, is encoded by the following transcript: HSSTROL3_T12 (sequences shown at the end of the application). The coding portion of the transcript HSSTROL3_T12 is shown in bold and this coding portion starts from position 24 and ends at position 1085. The transcript also has the following SNPs listed in Table 1079 (showing its position on the nucleotide sequence and listing another nucleic acid, the last column shows if the SNP is known, the mutein HSSTROL3_P9 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  As mentioned above, cluster HSSTROL3 is characterized by the sixteen segments listed in Table 2 above, the sequences of which are shown at the end of the application. These segments are part of the nucleic acid sequence, which are of particular interest and are individually described herein. A description of each segment of the invention is provided herein.

  The segment cluster HSSTROL3_node_6 of the present invention is supported by 14 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HSSTROL3_T5, HSSTROL3_T8, HSSTROL3_T9, HSSTROL3_T10, HSSTROL3_T11, and HSSTROL3_T12. Table 1080 below describes the start and end positions of this segment on each transcript.

  The segment cluster HSSTROL3_node_10 of the present invention is supported by 21 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HSSTROL3_T5, HSSTROL3_T8, HSSTROL3_T9, HSSTROL3_T10, HSSTROL3_T11, and HSSTROL3_T12. Table 1081 below describes the start and end positions of this segment on each transcript.

  The segment cluster HSSTROL3_node_13 of the present invention is supported by 36 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HSSTROL3_T5, HSSTROL3_T8, HSSTROL3_T9, HSSTROL3_T10, HSSTROL3_T11, and HSSTROL3_T12. Table 1082 below describes the start and end positions of this segment on each transcript.

  The segment cluster HSSTROL3_node_15 of the present invention is supported by 47 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HSSTROL3_T5, HSSTROL3_T8, HSSTROL3_T9, HSSTROL3_T10, HSSTROL3_T11, and HSSTROL3_T12. Table 1083 below describes the start and end positions of this segment on each transcript.

  The segment cluster HSSTROL3_node_19 of the present invention is supported by 63 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HSSTROL3_T5, HSSTROL3_T8, HSSTROL3_T9, HSSTROL3_T10, HSSTROL3_T11, and HSSTROL3_T12. Table 1084 below describes the start and end positions of this segment on each transcript.

  The segment cluster HSSTROL3_node_21 of the present invention is supported by 61 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HSSTROL3_T5, HSSTROL3_T8, HSSTROL3_T9, HSSTROL3_T10, HSSTROL3_T11, and HSSTROL3_T12. Table 1085 below describes the start and end positions of this segment on each transcript.

  The segment cluster HSSTROL3_node_24 of the present invention is supported by seven libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HSSTROL3_T8 and HSSTROL3_T9. Table 1086 below describes the start and end positions of this segment on each transcript.

  The segment cluster HSSTROL3_node_25 of the present invention is supported by 13 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HSSTROL3_T8. Table 1087 below describes the start and end positions of this segment on each transcript.

  The segment cluster HSSTROL3_node 26 according to the invention is supported by 55 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HSSTROL3_T5, HSSTROL3_T8, HSSTROL3_T9, and HSSTROL3_T11. Table 1088 below describes the start and end positions of this segment on each transcript.

  The segment cluster HSSTROL3_node_28 of the present invention is supported by 10 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HSSTROL3_T5, HSSTROL3_T9, and HSSTROL3_T10. Table 1089 below describes the start and end positions of this segment on each transcript.

  The segment cluster HSSTROL3_node_29 of the present invention is supported by 109 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HSSTROL3_T5, HSSTROL3_T8, HSSTROL3_T9, HSSTROL3_T10, HSSTROL3_T11, and HSSTROL3_T12. Table 1090 below describes the start and end positions of this segment on each transcript.

  According to an optional embodiment of the present invention, there is also provided a short segment associated with the above cluster. These segments are up to about 120 bp in length and are therefore included in the individual descriptions.

  The segment cluster HSSTROL3_node_11 of the present invention is supported by 25 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HSSTROL3_T5, HSSTROL3_T8, HSSTROL3_T9, HSSTROL3_T10, and HSSTROL3_T11. Table 1091 below describes the start and end positions of this segment on each transcript.

  The segment cluster HSSTROL3_node_17 of the present invention is supported by 45 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HSSTROL3_T5, HSSTROL3_T8, HSSTROL3_T9, HSSTROL3_T10, HSSTROL3_T11, and HSSTROL3_T12. Table 1092 below describes the start and end positions of this segment on each transcript.

  The segment cluster HSSTROL3_node_18 according to the invention can be found in the following transcripts: HSSTROL3_T5, HSSTROL3_T8, HSSTROL3_T9, HSSTROL3_T10, HSSTROL3_T11, and HSSTROL3_T12. Table 1093 below describes the start and end positions of this segment on each transcript.

  The segment cluster HSSTROL3_node_20 of the present invention is supported by one library. The number of libraries was determined as described above. This segment can be found in the following transcript: HSSTROL3_T11. Table 1094 below describes the start and end positions of this segment on each transcript.

  The segment cluster HSSTROL3_node_27 of the present invention is supported by 50 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HSSTROL3_T5, HSSTROL3_T8, HSSTROL3_T9, HSSTROL3_T10, HSSTROL3_T11, and HSSTROL3_T12. Table 1095 below describes the start and end positions of this segment on each transcript.

Mutated protein alignment against previously known proteins:
Sequence name: MM11_HUMAN

Sequence documentation:

Alignment of: HSSTROL3_P4 x MM11_HUMAN ..

Alignment segment 1/1:

Quality: 4444.00 Escore: 0
Matching length: 445 Total length: 445
Matching Percent Similarity: 99.78 Matching Percent Identity: 99.78
Total Percent Similarity: 99.78 Total Percent Identity: 99.78
Gaps: 0

Alignment:
....
1 MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQ 50
||||||||||||||||||||||||||||||||||||||||
1 MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQ 50
....
51 WHAALPSSPAPAPATQ EAPRPASS LRP PRC GVP PDS DGL SAR NRQ KRFVL 100
||||||||||||||||||||||||||||||||||||||||
51 WHAALPSSPAPAPATQ EAPRPASS LRP PRC GVP PDS DGL SAR NRQ KRFVL 100
....
101 SGGRWEKTDLTYRILRFPWQLVQEQVRQTM AEALKVWSDVTPLTFTEVHE 150
||||||||||||||||||||||||||||||||||||||||
101 SGGRWEKTDLTYRILRFPWQLVQEQVRQTM AEALKVWSDVTPLTFTEVHE 150
....
151 GRADIMIDFARYWHGDDDLPFDPGPGILAHAFFFPKTHREGDVHFDYDETWT 200
||||||||||||||||||||||||||||||||||||||||
151 GRAMIMIDFARYWDGDDLPLFPGPGILAHAFFFPKTHREGDVHFDYDETWT 200
....
201 IGDDQGTDLLQVAAHEFGHVLGLQHTTAAKALMFA YTFRYPLSLSPDDC 250
||||||||||||||||||||||||||||||||||||||||
201 IGDDQGTDLLQVAAHEFGHVLGLQHTTAAKALMFA YTFRYPLSLSPDDC 250
....
251 RGVQHLYGQPWPTVTSRTPALGPQAGIDTNEIAPLEPDAPPACEASFA 300
||||||||||||||||||||||||||||||||||||||||
251 RGVQHLYGQPWPTVTSRTPALGPQAGIDTNEIAPLEPDAPPACEASFA 300
....
301 VSTIRGELFFFKAGFVWRLRGGQLQPGYPalasRHWQGLPSPVDAAFEDA 350
||||||||||||||||||||||||||||||||||||||||
301 VSTIRGELFFFKAGFVWRLRGGQLQPGYPalasRHWQGLPSPVDAAFEDA 350
....
351 QGHIWFFQGAQYWVYDGEKPVLGPAPLTELGLVRFPVHAALVWGPEKNKI 400
||||||||||||||||||||||||||||||||||||||||
351 QGHIWFFQGAQYWVYDGEKPVLGPAPLTELGLVRFPVHAALVWGPEKNKI 400
....
401 YFFRGRDYWRFHPSTRRVDSPPVPRATTDWRGVPSEIDAAFQDADG 445
|||||||||||||||||||||||||||||||||||||||
401 YFFRGRDYWRFHPSTRRVDSPPVPRATTDWRGVPSEIDAAFQDADG 445






Sequence name: MM11_HUMAN

Sequence documentation:

Alignment of: HSSTROL3_P5 x MM11_HUMAN ..

Alignment segment 1/1:

Quality: 3566.00 Escore: 0
Matching length: 358 Total length: 358
Matching Percent Similarity: 99.72 Matching Percent Identity: 99.72
Total Percent Similarity: 99.72 Total Percent Identity: 99.72
Gaps: 0

Alignment:
....
1 MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQ 50
||||||||||||||||||||||||||||||||||||||||
1 MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQ 50
....
51 WHAALPSSPAPAPATQ EAPRPASS LRP PRC GVP PDS DGL SAR NRQ KRFVL 100
||||||||||||||||||||||||||||||||||||||||
51 WHAALPSSPAPAPATQ EAPRPASS LRP PRC GVP PDS DGL SAR NRQ KRFVL 100
....
101 SGGRWEKTDLTYRILRFPWQLVQEQVRQTM AEALKVWSDVTPLTFTEVHE 150
||||||||||||||||||||||||||||||||||||||||
101 SGGRWEKTDLTYRILRFPWQLVQEQVRQTM AEALKVWSDVTPLTFTEVHE 150
....
151 GRADIMIDFARYWHGDDDLPFDPGPGILAHAFFFPKTHREGDVHFDYDETWT 200
||||||||||||||||||||||||||||||||||||||||
151 GRAMIMIDFARYWDGDDLPLFPGPGILAHAFFFPKTHREGDVHFDYDETWT 200
....
201 IGDDQGTDLLQVAAHEFGHVLGLQHTTAAKALMFA YTFRYPLSLSPDDC 250
||||||||||||||||||||||||||||||||||||||||
201 IGDDQGTDLLQVAAHEFGHVLGLQHTTAAKALMFA YTFRYPLSLSPDDC 250
....
251 RGVQHLYGQPWPTVTSRTPALGPQAGIDTNEIAPLEPDAPPACEASFA 300
||||||||||||||||||||||||||||||||||||||||
251 RGVQHLYGQPWPTVTSRTPALGPQAGIDTNEIAPLEPDAPPACEASFA 300
....
301 VSTIRGELFFFKAGFVWRLRGGQLQPGYPalasRHWQGLPSPVDAAFEDA 350
||||||||||||||||||||||||||||||||||||||||
301 VSTIRGELFFFKAGFVWRLRGGQLQPGYPalasRHWQGLPSPVDAAFEDA 350

351 QGHIWFFQ 358
||||||||
351 QGHIWFFQ 358






Sequence name: MM11_HUMAN

Sequence documentation:

Alignment of: HSSTROL3_P7 x MM11_HUMAN ..

Alignment segment 1/1:

Quality: 3575.00 Escore: 0
Matching length: 359 Total length: 359
Matching Percent Similarity: 99.72 Matching Percent Identity: 99.72
Total Percent Similarity: 99.72 Total Percent Identity: 99.72
Gaps: 0

Alignment:
....
1 MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQ 50
||||||||||||||||||||||||||||||||||||||||
1 MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQ 50
....
51 WHAALPSSPAPAPATQ EAPRPASS LRP PRC GVP PDS DGL SAR NRQ KRFVL 100
||||||||||||||||||||||||||||||||||||||||
51 WHAALPSSPAPAPATQ EAPRPASS LRP PRC GVP PDS DGL SAR NRQ KRFVL 100
....
101 SGGRWEKTDLTYRILRFPWQLVQEQVRQTM AEALKVWSDVTPLTFTEVHE 150
||||||||||||||||||||||||||||||||||||||||
101 SGGRWEKTDLTYRILRFPWQLVQEQVRQTM AEALKVWSDVTPLTFTEVHE 150
....
151 GRADIMIDFARYWHGDDDLPFDPGPGILAHAFFFPKTHREGDVHFDYDETWT 200
||||||||||||||||||||||||||||||||||||||||
151 GRAMIMIDFARYWDGDDLPLFPGPGILAHAFFFPKTHREGDVHFDYDETWT 200
....
201 IGDDQGTDLLQVAAHEFGHVLGLQHTTAAKALMFA YTFRYPLSLSPDDC 250
||||||||||||||||||||||||||||||||||||||||
201 IGDDQGTDLLQVAAHEFGHVLGLQHTTAAKALMFA YTFRYPLSLSPDDC 250
....
251 RGVQHLYGQPWPTVTSRTPALGPQAGIDTNEIAPLEPDAPPACEASFA 300
||||||||||||||||||||||||||||||||||||||||
251 RGVQHLYGQPWPTVTSRTPALGPQAGIDTNEIAPLEPDAPPACEASFA 300
....
301 VSTIRGELFFFKAGFVWRLRGGQLQPGYPalasRHWQGLPSPVDAAFEDA 350
||||||||||||||||||||||||||||||||||||||||
301 VSTIRGELFFFKAGFVWRLRGGQLQPGYPalasRHWQGLPSPVDAAFEDA 350

351 QGHIWFFQG 359
|||||||||
351 QGHIWFFQG 359






Sequence name: MM11_HUMAN

Sequence documentation:

Alignment of: HSSTROL3_P8 x MM11_HUMAN ..

Alignment segment 1/1:

Quality: 2838.00 Escore: 0
Matching length: 286 Total length: 286
Matching Percent Similarity: 99.65 Matching Percent Identity: 99.65
Total Percent Similarity: 99.65 Total Percent Identity: 99.65
Gaps: 0

Alignment:
....
1 MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQ 50
||||||||||||||||||||||||||||||||||||||||
1 MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQ 50
....
51 WHAALPSSPAPAPATQ EAPRPASS LRP PRC GVP PDS DGL SAR NRQ KRFVL 100
||||||||||||||||||||||||||||||||||||||||
51 WHAALPSSPAPAPATQ EAPRPASS LRP PRC GVP PDS DGL SAR NRQ KRFVL 100
....
101 SGGRWEKTDLTYRILRFPWQLVQEQVRQTM AEALKVWSDVTPLTFTEVHE 150
||||||||||||||||||||||||||||||||||||||||
101 SGGRWEKTDLTYRILRFPWQLVQEQVRQTM AEALKVWSDVTPLTFTEVHE 150
....
151 GRADIMIDFARYWHGDDDLPFDPGPGILAHAFFFPKTHREGDVHFDYDETWT 200
||||||||||||||||||||||||||||||||||||||||
151 GRAMIMIDFARYWDGDDLPLFPGPGILAHAFFFPKTHREGDVHFDYDETWT 200
....
201 IGDDQGTDLLQVAAHEFGHVLGLQHTTAAKALMFA YTFRYPLSLSPDDC 250
||||||||||||||||||||||||||||||||||||||||
201 IGDDQGTDLLQVAAHEFGHVLGLQHTTAAKALMFA YTFRYPLSLSPDDC 250
....
251 RGVQHLYGQPWPTVTSRTPALGPQAGIDTNEIAPLE 286
|||||||||||||||||||||||||||||||||
251 RGVQHLYGQPWPTVTSRTPALGPQAGIDTNEIAPLE 286






Sequence name: MM11_HUMAN

Sequence documentation:

Alignment of: HSSTROL3_P9 x MM11_HUMAN ..

Alignment segment 1/1:

Quality: 3316.00 Escore: 0
Matching length: 343 Total length: 359
Matching Percent Similarity: 99.71 Matching Percent Identity: 99.71
Total Percent Similarity: 95.26 Total Percent Identity: 95.26
Gaps: 1

Alignment:
....
1 MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQ 50
||||||||||||||||||||||||||||||||||||||||
1 MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQ 50
....
51 WHAALPSSPAPAPATQ EAPRPASS LRP PRC GVP DPSD GL SAR NRQ K. ... 96
|||||||||||||||||||||||||||||||||||||||
51 WHAALPSSPAPAPATQ EAPRPASS LRP PRC GVP PDS DGL SAR NRQ KRFVL 100
....
97 ............ RIRLFPWQLVQEQVRQTM AEALKVWSDVTPLTFTEVHE 134
|||||||||||||||||||||||||||||||||||
101 SGGRWEKTDLTYRILRFPWQLVQEQVRQTM AEALKVWSDVTPLTFTEVHE 150
....
135 GRAMIMIDFARYWHGDDDLPFDPGPGILAHAFFFPKTHREGDVHFDYDETWT 184
||||||||||||||||||||||||||||||||||||||||
151 GRAMIMIDFARYWDGDDLPLFPGPGILAHAFFFPKTHREGDVHFDYDETWT 200
....
185 IGDDQGTDLLQVAAHEFGHVLGLQHTTAAKALMSAFYTFRYPLSLSPDDC 234
||||||||||||||||||||||||||||||||||||||||
201 IGDDQGTDLLQVAAHEFGHVLGLQHTTAAKALMFA YTFRYPLSLSPDDC 250
....
235 RGVQHLYGQPWPTVTSRTPALGPQAGIDTNEIAPLEPDAPPACEASFA 284
||||||||||||||||||||||||||||||||||||||||
251 RGVQHLYGQPWPTVTSRTPALGPQAGIDTNEIAPLEPDAPPACEASFA 300
....
285 VSTIRGELFFFKAGFVWRLRGGQLQPGYPalasRHWQGLPSPVDAAFEDA 334
||||||||||||||||||||||||||||||||||||||||
301 VSTIRGELFFFKAGFVWRLRGGQLQPGYPalasRHWQGLPSPVDAAFEDA 350

335 QGHIWFFQG 343
|||||||||
351 QGHIWFFQG 359

Expression of stromelysin-3 precursor HSSTROL3 transcripts detectable by the amplicon shown in the sequence name HSSTROL3seg24 in normal and cancerous lung tissue seg24, HSSTROL3seg24 amplicon (SEQ ID NO: 1675), and HSSTROL3seg24F (SEQ ID NO: 1673) and HSSTROL3seg24R ( SEQ ID NO: 1674) Expression of stromelysin-3 precursor (EC3.4.24.-) (matrix metalloproteinase-11) (MMP-11) (ST3) (SL-3) transcripts detectable by primers Measured by time PCR. In parallel, four housekeeping genes-PBGD (GenBank Accession No. BC019323, Amplicon – PBGD-Amplicon, SEQ ID No. 334), HPRT1 (GenBank Accession No. NM_000194, Amplicon – HPRT1- Amplicons, SEQ ID NO: 1297), Ubiquitin (GenBank Accession No. BC000449, Amplicon – Ubiquitin-Amplicon SEQ ID NO: 328), and SDHA (GenBank Accession No. NM_004168, Amplicon – SDHA-Amplicon The expression of SEQ ID NO: 331) was similarly measured. For each RT sample, the expression of the amplicon was normalized to the geometric mean of the housekeeping gene dose. The normalized amount of each RT sample is the center of the amount of normal postmortem (PM) samples (sample numbers 47-50, 90-93, 96-99 above, Table 2, "tissue samples in the test panel") Divide by the value to obtain the magnification of the upregulation of each sample relative to the median of normal PM samples.

  FIG. 39 is a histogram showing over expression of the stromelysin-3 precursor transcript in cancerous lung samples compared to normal samples. Values represent the average of duplicate experiments. Error bars indicate the obtained minimum and maximum values.

  As evident from FIG. 39, the expression of stromelysin-3 precursor transcripts detectable by the above amplicon in a cancer sample is a non-cancerous sample (sample no. 47-50, 90-93, 96-99, table 2, significantly higher than "tissue samples in the test panel"). Obviously, 13 out of 15 adenocarcinoma samples, 8 out of 16 squamous cell carcinoma samples, 3 out of 4 large cell carcinoma samples, 8 small cell carcinoma samples Overexpression of at least 5 fold was found in 7 of the

  The 5-fold overexpression threshold was found to be different between cancer and normal samples, checked by Fisher's exact test, P value 4.04E-04 for adenocarcinoma, squamous cell carcinoma 9.29E-02, 6.04E-02 for large cell carcinoma and 3.14E-03 for small cell carcinoma. The above values indicate that the results are statistically significant.

  Primer pairs are also optionally and preferably included within the scope of the present invention, for example, in the above experiments the following primers were used only as a non-limiting illustration of suitable primer pairs: HSSTROL3seg24F forward primer and HSSTROL3seg24R reverse Direction primer.

  The present invention also preferably includes any amplicon obtained by use of any suitable primer pair (e.g. in the above experiments) and obtained the following amplicons only as a non-limiting illustration of a suitable amplicon : HSSTROL3seg24.

Forward primer (SEQ ID NO: 1673): ATTTCCATCCTCAACTGGCAGA
Reverse primer (SEQ ID NO: 1674): TGCCCTGGAACCCACG
Amplicon (SEQ ID NO: 1675): ATTTCCATCCTCAACTGGCAGAGATGAGAGCCTTGAGCATTGCAGATGCGAGGACTC ACAAATGA AGGCACAGCAGGGAC AACCTGCGTGGGTTCAGGGCA

Expression of the stromelysin-3 precursor HSSTROL3 transcript detectable by the amplicon shown in the sequence name HSSTROL3seg24 in different normal tissues Detection by the HSSTROL3seg24 amplicon (SEQ ID NO: 1675) and HSSTROL3seg24F (SEQ ID NO: 1673) and HSSTROL3seg24R (SEQ ID NO: 1674) The expression of possible stromelysin-3 precursor transcripts was measured by real time PCR. In parallel, four housekeeping genes-ubiquitin (GenBank Accession No. BC000449, Amplicon – Ubiquitin-Amplicon SEQ ID No. 328), and SDHA (GenBank Accession No. NM_004168, Amplicon – SDHA- The expression of amplicon SEQ ID NO: 331), RPL19 (GenBank Accession No. NM_000981, RPL19 amplicon, SEQ ID NO: 1630), TATA box (GenBank Accession No. NM_003194, TATA amplicon, SEQ ID NO: 1633) was similarly measured. For each RT sample, the expression of the amplicon was normalized to the geometric mean of the housekeeping gene dose. The normalized volume of each RT sample is divided by the median volume of lung samples (Sample Nos. 15-17 above, Table 2, "Tissue Samples in Normal Panel"), and each sample relative to the median lung sample The value of relative expression of was obtained.

Forward primer (SEQ ID NO: 1673): ATTTCCATCCTCAACTGGCAGA
Reverse primer (SEQ ID NO: 1674): TGCCCTGGAACCCACG
Amplicon (SEQ ID NO: 1675): ATTTCCATCCTCAACTGGCAGAGATGAGAGCCTTGAGCATTGCAGATGCGAGGACTC ACAAATGA AGGCACAGCAGGGAC AACCTGCGTGGGTTCAGGGCA

  The results are shown in FIG. 40, which shows the expression of stromelysin-3HSSTROL3 transcripts detectable by the amplicon shown in the sequence name HSSTROL3seg24 in different normal tissues.

Expression of homo-Sapiens matrix metalloproteinase-11 (stromelysin 3) (MMP11) HSSTROL3 transcripts detectable by the amplicon shown in the sequence name HSSTROL3seg20-21 in normal and cancerous lung tissue seg20-21, HSSTROL3seg20-21 amplicon (Sequence ID No. 1678) and expression of the expression of a real Sapiens matrix metalloproteinase-11 (Stromelysin 3) (MMP 11) transcript detectable by the primers HSSTROL3seg20-21F (SEQ ID No. 1676) and HSSTROL3seg20-21R (SEQ ID No. 1677) Measured by time PCR. In parallel, four housekeeping genes-PBGD (GenBank Accession No. BC019323, Amplicon – PBGD-Amplicon, SEQ ID No. 334), HPRT1 (GenBank Accession No. NM_000194, Amplicon – HPRT1- Amplicons, SEQ ID NO: 1297), Ubiquitin (GenBank Accession No. BC000449, Amplicon – Ubiquitin-Amplicon SEQ ID NO: 328), and SDHA (GenBank Accession No. NM_004168, Amplicon – SDHA-Amplicon The expression of SEQ ID NO: 331) was similarly measured. For each RT sample, the expression of the amplicon was normalized to the geometric mean of the housekeeping gene dose. Normalized PM samples by dividing the normalized volume of each RT sample by the median volume of normal postmortem (PM) samples (sample numbers 47-50, 90-93, 96-99, Table 2 above) Magnifications of upregulation of each sample to the median of were obtained.

  FIG. 71 is a histogram showing the over expression of the homo-sapiens matrix metalloproteinase 11 (stromelysin 3) (MMP11) transcript in cancerous lung samples compared to normal samples.

  As apparent from FIG. 71, the expression of the homo-Sapiens matrix metalloproteinase 11 (stromelysin 3) (MMP 11) transcript detectable by the above amplicon in the cancer sample was determined by the non-cancerous sample (Sample Nos. 46-50, 90-93, 96-99, significantly higher than Table 2). Clearly, 11 out of 15 adenocarcinoma samples, 6 out of 16 squamous cell carcinoma samples, 1 out of 4 large cell carcinoma samples, 8 small cell carcinoma samples Overexpression of at least 6-fold was found in 6 of them.

  Primer pairs are also optionally and preferably included within the scope of the present invention, for example, in the above experiments the following primers were used only as non-limiting examples of suitable primer pairs: HSSTROL3seg20-21F forward primer and HSSTROL3 seg 20-21 R reverse primer.

  The present invention also preferably includes any amplicon obtained by use of any suitable primer pair (e.g. in the above experiments) and obtained the following amplicons only as a non-limiting illustration of a suitable amplicon : HSSTROL3seg 20-21.

Primer:
Forward primer HSSTROL3seg20-21F (SEQ ID NO: 1676): TCTGCTGGCCACTGTGACTG
Reverse primer HSSTROL3seg20-21R (SEQ ID NO: 1677): GAAGAAAAAGAGCTGCCTCG
Amplicon HSSTROL3 seg 20-21 (SEQ ID NO: 1678): TCTGCTGGCCACTGTGACTGCAGCATATGCCCTCAAGCATGTGTCCCTCTCTCCCACCCCAGCCAGACGGCCCCGCCCAGATGGCCTGCTAGAGGCCTCCTTTGACGCGGTCTCACCATCCGAGGCGAGCTCTTTTTTCTCTC

Expression of homo-Sapiens matrix metalloproteinase-11 (stromelysin 3) (MMP11) HSSTROL3 transcripts detectable by an amplicon as shown in the sequence name HHSSTROL3 junc 21-27 in normal and cancerous lung tissue junc 21-27, HSSTROL 3 junc 21-27 amplicon (Sequence ID No. 1681) and expression of real Sapiens matrix metalloproteinase-11 (Stromelysin 3) (MMP11) transcripts detectable by primers HSSTROL3 junc 21-27 F (SEQ ID NO: 1679) and HSSTROL 3 junc 21-27 R (SEQ ID NO: 1680) Measured by time PCR. In parallel, four housekeeping genes-PBGD (GenBank Accession No. BC019323, Amplicon – PBGD-Amplicon, SEQ ID No. 334), HPRT1 (GenBank Accession No. NM_000194, Amplicon – HPRT1- Amplicons, SEQ ID NO: 1297), Ubiquitin (GenBank Accession No. BC000449, Amplicon – Ubiquitin-Amplicon SEQ ID NO: 328), and SDHA (GenBank Accession No. NM_004168, Amplicon – SDHA-Amplicon The expression of SEQ ID NO: 331) was similarly measured. For each RT sample, the expression of the amplicon was normalized to the geometric mean of the housekeeping gene dose. Normalized PM samples by dividing the normalized volume of each RT sample by the median volume of normal postmortem (PM) samples (sample numbers 47-50, 90-93, 96-99, Table 2 above) Magnifications of upregulation of each sample to the median of were obtained.

  Figure 72 is a histogram showing over expression of the homo-sapiens matrix metalloproteinase 11 (stromelysin 3) (MMP11) transcript in cancerous lung samples compared to normal samples.

  As apparent from FIG. 72, the expression of the homo-Sapiens matrix metalloproteinase 11 (stromelysin 3) (MMP 11) transcript that is detectable by the above amplicon in the cancer sample is a non-cancerous sample (sample numbers 46-50, 90-93, 96-99, significantly higher than Table 2). Obviously, 15 out of 15 adenocarcinoma samples, 13 out of 16 squamous cell carcinoma samples, 3 out of 4 large cell carcinoma samples, 8 small cell carcinoma samples Overexpression of at least 10-fold was found in 5 of them.

  Primer pairs are also optionally and preferably included within the scope of the present invention, for example, in the above experiments the following primers were used only as non-limiting examples of suitable primer pairs: HSSTROL3 junc21-27F forward primer and HSSTROL3 junc 21-27 R reverse primer.

  The present invention also preferably includes any amplicon obtained by use of any suitable primer pair (e.g. in the above experiments) and obtained the following amplicons only as a non-limiting illustration of a suitable amplicon : HSSTROL3 junc 21-27.

Primer:
Forward primer HSSTROL3junc 21-27F (SEQ ID NO: 1679): ACATTTGGTTCTTCCAAGGGACTAC
Reverse primer HSSTROL3junc 21-27R (SEQ ID NO: 1680): TCGATCTCAGAGGGCACCC
Amplicon HSSTROL3 junc 21-27 (SEQ ID NO: 1681): ACATTTGGTTCTTCCAAGGGACTACTGGCGTTTTCCCCCCCAGCACCCGGCAGTCAGCAGTCCCGTGCCCCGCAGGGCCACTGACTGGAGAGGGGTGCCTCTGGAGATCGA

Description of cluster HUMTREFAC The cluster HUMTREFAC is characterized by two transcripts and 7 segments of interest, the names of which are given in Tables 1096 and 1097 respectively, and the sequence itself is given at the end of the application. Selected protein variants are shown in Table 1098.

  These sequences are also known as Trefoil factor 3 precursor (SwissProt accession identifier TFF3_HUMAN), a synonym intestinal trefoil factor, hP1.B, which is a known protein, previously known herein as a protein. It is a variant of (known) (SEQ ID NO: 1456).

  The protein trefoil factor 3 precursor is known or considered to have the following functions: It may play a role in promoting cell migration (cell migration promoting factor). The sequence of the protein trefoil factor 3 precursor is shown at the end of the application as "trefoil factor 3 precursor amino acid sequence". Known polymorphisms of this sequence are shown in Table 1099.

  Localization of the protein trefoil factor 3 precursor is considered secretion.

  The following GO annotation applies to previously known proteins. The following annotations have been found: extracellular response that is annotated related to biological processes, defense response, digestion, and annotated related to cellular components.

  GO assignments can be made at one or more http: // www. expasy. SwissProt / TremBl Protein knowledgebase available from ch / sprot / or http: // www. ncbi. nlm. nih. Depends on Locuslink available from gov / projects / LocusLink /.

  The cluster HUMTREFAC can be used as a diagnostic marker by overexpression of transcripts of this cluster in cancer. The expression of such transcripts in normal tissues is also shown by the method previously described. The terms "numbers" in the right column of the table and the numbers on the y-axis of FIG. 41 refer to the weighted expression of ESTs in each category as "ppm" (the ppm of ESTs of a particular cluster in this category by ppm Ratio of expression to expression of all ESTs).

  In general, as shown for the histograms in FIG. 41 and Table 1100, the following results were obtained. This cluster was overexpressed (at least at minimal levels) in the following pathological conditions: a mixture of malignant tumors from different tissues, malignant breast cancer, pancreatic cancer, and prostate cancer.

  As mentioned above, cluster HUMTREFAC is characterized by the two transcripts listed in Table 1 above. These transcripts encode proteins which are variants of the protein trefoil factor 3 precursor. A description of each mutein of the invention is provided herein.

  The mutein HUMTREFAC_PEA_2_P7 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript HUMTREFAC_PEA_2_T5. The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein HUMTREFAC_PEA_2_P7 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows the SNPs as shown in Table 1102) It indicates whether it is known and the presence of a known SNP in the mutant protein HUMTREFAC_PEA_2_P7 sequence supports the putative sequence of this mutant protein of the invention).

  The mutein, HUMTREFAC_PEA_2_P7, is encoded by the following transcript: HUMTREFAC_PEA_2_T5 (sequences shown at the end of the application). The code portion of the transcript HUMTREFAC_PEA_2_T5 is shown in bold, starting from position 278 and ending at position 688. The transcript also has the following SNPs listed in Table 1103 (showing its position on the nucleotide sequence, listing another nucleic acid, the last column shows if the SNP is known, mutein HUMTREFAC_PEA_2_P7 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein HUMTREFAC_PEA_2_P8 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript HUMTREFAC_PEA_2_T4. An alignment to a known protein (trefoil factor 3 precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Reporting of the comparison between HUMTREFAC_PEA_2_P8 and TFF3_HUMAN 1. A polypeptide having a first amino acid sequence corresponding to amino acids 1 to 27 of TFF3_HUMAN and also to amino acids 1 to 27 of HUMTREFAC_PEA_2_P8 at least 90% homologous to MAARALC ML GLVLALL SS SSEAE EYVGL Said second amino acid sequence comprising a second amino acid sequence which is at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous; An isolated chimeric polypeptide encoding HUMTREFAC_PEA_2_P8, wherein the two amino acid sequences are in contiguous and sequential order.

  2. HUMTREFAC_PEA_2_P8 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence WKVHLPKGEGFSSG in HUMTREFAC_PEA_2_P8 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein HUMTREFAC_PEA_2_P8 also has the following non-silent SNPs (single nucleotide polymorphisms) (indicating its position on the amino acid sequence, listing other amino acids, and the last column, SNPs, as shown in Table 1104) It indicates whether it is known and the presence of a known SNP in the mutant protein HUMTREFAC_PEA_2_P8 sequence supports the putative sequence of this mutant protein of the invention).

  The mutein, HUMTREFAC_PEA_2_P8, is encoded by the following transcript: HUMTREFAC_PEA_2_T4 (sequences shown at the end of the application). The code portion of the transcript HUMTREFAC_PEA_2_T4 is shown in bold, starting at position 278 and ending at position 400. The transcript also has the following SNPs listed in Table 1105 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, the mutein HUMTREFAC_PEA_2_P8 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  As mentioned above, cluster HUMTREFAC is characterized by the seven segments listed in Table 2 above, the sequence of which is shown at the end of the application. These segments are part of the nucleic acid sequence, which are of particular interest and are individually described herein. A description of each segment of the invention is provided herein.

  The segment cluster HUMTREFAC_PEA_2_node_0 of the present invention is supported by 188 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMTREFAC_PEA_2_T4 and HUMTREFAC_PEA_2_T5. Table 1106 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMTREFAC_PEA_2_node_9 of the present invention is supported by 150 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMTREFAC_PEA_2_T4 and HUMTREFAC_PEA_2_T5. Table 1107 below describes the start and end positions of this segment on each transcript.

  According to an optional embodiment of the present invention, there is also provided a short segment associated with the above cluster. These segments are up to about 120 bp in length and are therefore included in the individual descriptions.

  The segment cluster HUMTREFAC_PEA_2_node_2 of the present invention is supported by 4 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMTREFAC_PEA_2_T4. Table 1108 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMTREFAC_PEA_2_node_3 of the present invention is supported by 10 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMTREFAC_PEA_2_T4 and HUMTREFAC_PEA_2_T5. Table 1109 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMTREFAC_PEA_2_node_4 of the present invention is supported by 197 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMTREFAC_PEA_2_T4 and HUMTREFAC_PEA_2_T5. Table 1110 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMTREFAC_PEA_2_node_5 of the present invention is supported by 187 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMTREFAC_PEA_2_T4 and HUMTREFAC_PEA_2_T5. Table 1111 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMTREFAC_PEA_2_node_8 according to the invention can be found in the following transcripts: HUMTREFAC_PEA_2_T4 and HUMTREFAC_PEA_2_T5. Table 1112 below describes the start and end positions of this segment on each transcript.

Mutated protein alignment against previously known proteins:
Sequence name: TFF3_HUMAN

Sequence documentation:

Alignment of: HUMTREFAC_PEA_2_P8 x TFF3_HUMAN ..

Alignment segment 1/1:

Quality: 246.00 Escore: 0
Matching length: 27 Total length: 27
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
.
1 MAARALCMLGLVLALLSSSSAEEYVGL 27
|||||||||||||||||||||||||
1 MAARALCMLGLVLALLSSSSAEEYVGL 27

Description of cluster HSS100 PCB The cluster HSS100 PCB features one transcript and three segments of interest, the names of which are given in Tables 1113 and 1114 respectively, and the sequence itself is given at the end of the application. Selected protein variants are shown in Table 1115.

  These sequences are referred to herein as proteins previously known and are variants of S-100P protein (SwissProt accession identifier S10P_HUMAN) (SEQ ID NO: 1457), a known protein that binds to two calcium ions. It is.

  Protein S-100P The protein sequence is shown at the end of the application as "S-100P protein amino acid sequence". Known polymorphisms of this sequence are shown in Table 1116.

  The following GO annotation applies to previously known proteins. The following annotations were found: calcium binding, protein binding, which are annotations related to molecular function.

  GO assignments can be made at one or more http: // www. expasy. SwissProt / TremBl Protein knowledgebase available from ch / sprot / or http: // www. ncbi. nlm. nih. Depends on Locuslink available from gov / projects / LocusLink /.

  Cluster HSS100 PCB can be used as a diagnostic marker by overexpression of transcripts of this cluster in cancer. The expression of such transcripts in normal tissues is also shown by the method previously described. The terms "numbers" in the right column of the table and the numbers on the y-axis of Fig. 42 refer to the weighted expression of ESTs in each category as "ppm" (the ppm of ESTs of a particular cluster in this category by ppm Ratio of expression to expression of all ESTs).

  In general, as shown for the histograms in FIG. 42 and Table 1117, the following results were obtained. This cluster was overexpressed (at least at the minimum level) in the following pathological conditions: a mixture of malignant tumors from different tissues.

  As mentioned above, cluster HSS100 PCB is characterized by one transcript as listed in Table 1 above. These transcripts encode a protein which is a mutated form of protein S-100P protein. A description of each mutein of the invention is provided herein.

  The mutein HSS100PCB_P3 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript HSS100PCB_T1. The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein HSS100PCB_P3 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows SNPs as shown in Table 1119) It indicates whether it is known and the presence of a known SNP in the mutant protein HSS100PCB_P3 sequence supports the predicted sequence of this mutant protein of the invention).

  The mutein, HSS100PCB_P3, is encoded by the following transcript: HSS100PCB_T1 (sequences shown at the end of the application). The code portion of the transcript HSS100PCB_T1 is shown in bold and this code portion starts at position 1057 and ends at position 1533. The transcript also has the following SNPs listed in Table 1120 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, the mutein HSS100PCB_P3 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  As mentioned above, cluster HSS100 PCB is characterized by the three segments listed in Table 2 above, the sequence of which is shown at the end of the application. These segments are part of the nucleic acid sequence, which are of particular interest and are individually described herein. A description of each segment of the invention is provided herein.

  The segment cluster HSS100PCB_node_3 of the present invention is supported by 16 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HSS100 PCB_T1. Table 1121 below describes the start and end positions of this segment on each transcript.

  The segment cluster HSS100PCB_node_4 of the present invention is supported by 29 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HSS100 PCB_T1. Table 1122 below describes the start and end positions of this segment on each transcript.

  The segment cluster HSS100PCB_node_5 of the present invention is supported by 141 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HSS100 PCB_T1. Table 1124 below describes the start and end positions of this segment on each transcript.

Description of cluster HSU33147 Cluster HSU33147 is characterized by 2 transcripts and 5 segments of interest, the names of which are given in Tables 1125 and 1126 respectively, and the sequence itself is given at the end of the application. Selected protein variants are shown in Table 1127.

  These sequences are also known as mammabinin A precursor (SwissProt accession identifier MGBA_HUMAN, synonyms mammaglobin 1, secretoglobin family 2A member 2), which is a known protein, previously known herein as a protein (SEQ ID NO: 1416).

  The sequence of the protein mammaglobin A precursor is shown at the end of the application as "Mammaglobin A precursor amino acid sequence".

  Clinical / therapeutic applications in humans (e.g. as targets for antibodies or small molecules and / or as direct therapy) are being investigated and available information related to these investigations is: Potential pharmaceutically relevant or therapeutically relevant activities of previously known proteins are: immunostimulants. The therapeutic role of proteins displayed by clusters is expected. Because information is present in drug databases or public databases (eg, above) that may or may not be used to apply this protein or a portion thereof to a potential treatment (anti-cancer drug), the clusters Assigned to this area.

  The following GO annotation applies to previously known proteins. The following annotations were found: steroid binding, which is an annotation related to molecular function.

  GO assignments can be made at one or more http: // www. expasy. SwissProt / TremBl Protein knowledgebase available from ch / sprot / or http: // www. ncbi. nlm. nih. Depends on Locuslink available from gov / projects / LocusLink /.

  Cluster HSU33147 can be used as a diagnostic marker by overexpression of transcripts of this cluster in cancer. The expression of such transcripts in normal tissues is also shown by the method previously described. The term “number” in the left column of the table and the number on the y-axis of FIG. 43 refer to the weighted expression of ESTs in each category as “ppm” (for ESTs of a particular cluster in this category by ppm Ratio of expression to expression of all ESTs).

  In general, as shown for the histograms in FIG. 43 and Table 1128, the following results were obtained. This cluster was overexpressed (at least at the minimum level) in the following pathological conditions: a mixture of malignant tumors from different tissues.

  As mentioned above, cluster HSU33147 is characterized by the two transcripts listed in Table 1 above. These transcripts encode a protein which is a mutated form of the protein mammaglobin A precursor. A description of each mutein of the invention is provided herein.

  The mutein HSU33147_PEA_1_P5 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript HSU33147_PEA_1_T1. An alignment to a known protein (matunabin A precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between HSU33147_PEA_1_P5 and MGBA_HUMAN 1. The corresponding amino acids 1 to 78 of MGBA_HUMAN, and corresponding to amino acids 1 to 78 of HSU33147_PEA_1_P5 MKLL MVLLA ALS Q HC YAG SGC PLLEN VIS K TIN PQ VSKTEYKELL QE FIDDNATTNAID ELKE CFLN Q TDE TLS NVE and the corresponding amino acids Isolated that encodes HSU33147_PEA_1_P5, which also comprises the corresponding QLIYDSSLCDLF and a second amino acid sequence at least 90% homologous, said first amino acid sequence and the second amino acid sequence being adjacent and in sequential order Chimeric polypeptide.

  2. Length “n” (wherein n is at least about 10 amino acids long, optionally at least about 20 amino acids long, preferably at least about 30 amino acids long, more preferably at least about 40 amino acids long, most preferably at least about 50 amino acids long, at least two amino acids comprising EQ, starting from any of the following structures: amino acids nos. 78-x to 78, amino acids nos. 79 + ((n-2)-x) (formula An isolated chimeric polypeptide encoding an edge portion of HSU33147_PEA_1_P5, comprising a polypeptide, having a sequence terminating in: x) varying from 0 to n-2).

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The glycosylation sites of the mutant protein HSU33147_PEA_1_P5 compared to the known protein martuna bin A precursor are shown in Table 1130 (showing its position on the amino acid sequence in the first column, the second column has mutations in glycosylation sites) The presence or absence in the protein is indicated and the last column indicates whether this position is different on the mutated protein).

  The mutein, HSU33147_PEA_1_P5, is encoded by the following transcript: HSU33147_PEA_1_T1 (sequences shown at the end of the application). The code portion of the transcript HSU33147_PEA_1_T1 is shown in bold, starting at position 72 and ending at position 341. The transcript also has the following SNPs listed in Table 1131 (showing its position on the nucleotide sequence and listing another nucleic acid, the last column shows whether the SNP is known, mutein HSU33147_PEA_1_P5 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  As mentioned above, cluster HSU33147 is characterized by the five segments listed in Table 2 above, the sequence of which is shown at the end of the application. These segments are part of the nucleic acid sequence, which are of particular interest and are individually described herein. A description of each segment of the invention is provided herein.

  The segment cluster HSU33147_PEA_1_node_0 of the present invention is supported by 38 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HSU33147_PEA_1_T1 and HSU33147_PEA_1_T2. Table 1132 below describes the start and end positions of this segment on each transcript.

  The segment cluster HSU33147_PEA_1_node_2 of the present invention is supported by 44 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HSU33147_PEA_1_T1 and HSU33147_PEA_1_T2. Table 1133 below describes the start and end positions of this segment on each transcript.

  The segment cluster HSU33147_PEA_1_node_4 of the present invention is supported by three libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HSU33147_PEA_1_T2. Table 1134 below describes the start and end positions of this segment on each transcript.

  The segment cluster HSU33147_PEA_1_node_7 of the present invention is supported by 35 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HSU33147_PEA_1_T1. Table 1135 below describes the start and end positions of this segment on each transcript.

  According to an optional embodiment of the present invention, there is also provided a short segment associated with the above cluster. These segments are up to about 120 bp in length and are therefore included in the individual descriptions.

  The segment cluster HSU33147_PEA_1_node_3 of the invention can be found in the following transcript: HSU33147_PEA_1_T2. Table 1136 below describes the start and end positions of this segment on each transcript.

Mutated protein alignment against previously known proteins:
Sequence name: MGBA_HUMAN

Sequence documentation:

Alignment of: HSU33147_PEA_1_P5 x MGBA_HUMAN ..

Alignment segment 1/1:

Quality: 776.00 Escore: 0
Matching length: 90 Total length: 93
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 96.77 Total Percent Identity: 96.77
Gaps: 1

Alignment:
....
1 MKLLMVLMLAALSQHCYAGSGCPLLENVISKTINPQVSKTEYKELLQEFI 50
||||||||||||||||||||||||||||||||||||||||
1 MKLLMVLMLAALSQHCYAGSGCPLLENVISKTINPQVSKTEYKELLQEFI 50
....
51 DDNATTNAIDELKECFLNQTDETLSNVE ... QLIYDSSLCDLF 90
||||||||||||||||||||||||||||||||||
51 DDNATTNAIDELKECFLNQTDETLSNVEVFMQLIYDSSLCDLF 93

Description of Cluster R20779 Cluster R20779 is characterized by one transcript and 24 segments of interest, the names of which are shown in Tables 1137 and 1138 respectively, and the sequence itself is shown at the end of the application. Selected protein variants are shown in Table 1139.

  These sequences are also known as stanniocalcin 2 precursor (SwissProt accession identifier STC2_HUMAN, the synonym STC-2, stanniocalcin related protein, CTCRP, STC related protein, which is a known protein previously referred to herein as a protein). It is a variant of (known) (SEQ ID NO: 1458).

  The protein stanniocalcin 2 precursor is known or considered to have the following function: It has an anti-low calcium effect on calcium and phosphate homeostasis. The sequence of the protein stanniocalcin 2 precursor is shown at the end of the application as "stanniocalcin 2 precursor amino acid sequence". Localization of the protein stanniocalcin 2 precursor is considered to be secreted (possibly).

  The following GO annotation applies to previously known proteins. The following annotations have been found: cell surface receptor binding signaling that is annotated in connection with biological processes, cell-cell signaling, nutrient response pathways, hormone that is an annotation related to molecular function, Extracellular, annotating related to cellular components.

  GO assignments can be made at one or more http: // www. expasy. SwissProt / TremBl Protein knowledgebase available from ch / sprot / or http: // www. ncbi. nlm. nih. Depends on Locuslink available from gov / projects / LocusLink /.

  Cluster R20779 can be used as a diagnostic marker by overexpression of transcripts of this cluster in cancer. The expression of such transcripts in normal tissues is also shown by the method previously described. The terms “number” in the right column of the table and the numbers on the y-axis of FIG. 44 refer to the weighted expression of ESTs in each category as “ppm” (the ppm of ESTs of a particular cluster in this category by ppm Ratio of expression to expression of all ESTs).

  In general, as shown for the histograms in FIG. 44 and Table 1140, the following results were obtained. This cluster was overexpressed (at least at minimal levels) in the following pathological conditions: epithelial malignancies, a mixture of malignancies from different tissues, and malignant lung tumors.

  As mentioned above, cluster R20779 is characterized by one transcript as listed in Table 1 above. These transcripts encode proteins which are variants of the protein Stanniocalcin 2 precursor. A description of each mutein of the invention is provided herein.

  The mutein R20779_P2 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript R20779_T7. An alignment to a known protein (stanniocalcin 2 precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between R20779_P2 and STC2_HUMAN Corresponding to amino acids 1-169 of STC2_HUMAN, first amino acid sequence at least 90% homologous to the corresponding MCAERLGQFMTLALVLATFDPARGTDATNPPEGPQDRSSQQKGRLSLQNTAEIQHCLVNAGDVGCGVFECFENNSCEIRGLHGICMTFLHNAGKFDAQGKSFIKDALKCKAHALRHRFGCISRKCPAIREMVSQLQRECYLKHDLCAAAQENTRVIVEMIHFKDLLLHE to amino acids 1-169 of R20779_P2, the polypeptide having a sequence corresponding to CYKIEITMPKRRKVKLRD to amino acid 170-187 of R20779_P2 At least 70%, optionally at least 80%, preferably at least A second amino acid sequence that is 5%, more preferably at least 90%, most preferably at least 95% homologous, the first amino acid sequence and the second amino acid sequence being adjacent and in a contiguous order , An isolated chimeric polypeptide encoding R20779_P2.

  2. R20779_P2 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence CYKIEITMPKRRKVKLRD in R20779_P2 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein R20779_P2 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows SNPs as shown in Table 1142) It is shown whether it is known and the presence of known SNPs in the mutein R20779_P2 sequence supports the deduced sequence of this mutein of the invention).

  The glycosylation sites of mutant protein R20779_P2 compared to the known protein stanniocalcin 2 precursor are shown in Table 1143 (showing its position on the amino acid sequence in the first column, the second column has a mutation site with glycosylation site Indicates if it is present in the last column and indicates if this position differs on the mutein).

  The mutein R20779_P2 is encoded by the following transcript: R20779_T7 (sequences shown at the end of the application). The coding portion of the transcript R20779_T7 is shown in bold and this coding portion starts at position 1397 and ends at position 1957. The transcript also has the following SNPs listed in Table 1144 (showing its position on the nucleotide sequence and listing another nucleic acid, the last column shows whether the SNP is known, mutein R20779_P2 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  As mentioned above, cluster R20779 is characterized by the 24 segments listed in Table 2 above, the sequence of which is shown at the end of the application. These segments are part of the nucleic acid sequence, which are of particular interest and are individually described herein. A description of each segment of the invention is provided herein.

  The segment cluster R20779_node_0 of the present invention is supported by 31 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R20779_T7. Table 1145 below describes the start and end positions of this segment on each transcript.

  The segment cluster R20779_node_2 of the present invention is supported by 55 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R20779_T7. Table 1146 below describes the start and end positions of this segment on each transcript.

  The segment cluster R20779_node_7 of the present invention is supported by 63 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R20779_T7. Table 1147 below describes the start and end positions of this segment on each transcript.

  The segment cluster R20779_node_9 of the present invention is supported by 66 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R20779_T7. Table 1148 below describes the start and end positions of this segment on each transcript.

  The segment cluster R20779_node_18 of the present invention is supported by 61 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R20779_T7. Table 1149 below describes the start and end positions of this segment on each transcript.

  The segment cluster R20779_node_21 of the present invention is supported by 106 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R20779_T7. Table 1150 below describes the start and end positions of this segment on each transcript.

  The segment cluster R20779_node_24 of the present invention is supported by 100 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R20779_T7. Table 1151 below describes the start and end positions of this segment on each transcript.

  The segment cluster R20779_node_27 of the present invention is supported by 26 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R20779_T7. Table 1152 below describes the start and end positions of this segment on each transcript.

  The segment cluster R20779_node_28 of the present invention is supported by 31 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R20779_T7. Table 1153 below describes the start and end positions of this segment on each transcript.

  The segment cluster R20779_node_30 of the present invention is supported by 34 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R20779_T7. Table 1154 below describes the start and end positions of this segment on each transcript.

  The segment cluster R20779_node_31 of the present invention is supported by 46 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R20779_T7. Table 1155 below describes the start and end positions of this segment on each transcript.

  The segment cluster R20779_node_32 of the present invention is supported by 88 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R20779_T7. Table 1156 below describes the start and end positions of this segment on each transcript.

  According to an optional embodiment of the present invention, there is also provided a short segment associated with the above cluster. These segments are up to about 120 bp in length and are therefore included in the individual descriptions.

  The segment cluster R20779_node_1 of the present invention is supported by 27 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R20779_T7. Table 1157 below describes the start and end positions of this segment on each transcript.

  The segment cluster R20779_node_3 of the present invention is supported by 52 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R20779_T7. Table 1158 below describes the start and end positions of this segment on each transcript.

  The segment cluster R20779_node_10 according to the invention can be found in the following transcript: R20779_T7. Table 1159 below describes the start and end positions of this segment on each transcript.

  The segment cluster R20779_node_11 of the present invention is supported by 58 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R20779_T7. Table 1160 below describes the start and end positions of this segment on each transcript.

  The segment cluster R20779_node_14 of the present invention is supported by one library. The number of libraries was determined as described above. This segment can be found in the following transcript: R20779_T7. Table 1161 below describes the start and end positions of this segment on each transcript.

  The segment cluster R20779_node_17 of the present invention is supported by 54 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R20779_T7. Table 1162 below describes the start and end positions of this segment on each transcript.

  The segment cluster R20779_node_19 of the invention can be found in the following transcript: R20779_T7. Table 1163 below describes the start and end positions of this segment on each transcript.

  The segment cluster R20779_node_20 of the present invention is supported by 53 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R20779_T7. Table 1164 below describes the start and end positions of this segment on each transcript.

  The segment cluster R20779_node_22 of the present invention is supported by 76 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R20779_T7. Table 1165 below describes the start and end positions of this segment on each transcript.

  The segment cluster R20779_node_23 of the present invention is supported by 81 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R20779_T7. Table 1166 below describes the start and end positions of this segment on each transcript.

  The segment cluster R20779_node_25 according to the invention can be found in the following transcript: R20779_T7. Table 1167 below describes the start and end positions of this segment on each transcript.

  The segment cluster R20779_node_29 according to the invention can be found in the following transcript: R20779_T7. Table 1168 below describes the start and end positions of this segment on each transcript.

Mutated protein alignment against previously known proteins:
Sequence name: STC2_HUMAN

Sequence documentation:

Alignment of: R20779_P2 x STC2_HUMAN ..

Alignment segment 1/1:

Quality: 1688.00 Escore: 0
Matching length: 171 Total length: 171
Matching Percent Similarity: 99.42 Matching Percent Identity: 99.42
Total Percent Similarity: 99.42 Total Percent Identity: 99.42
Gaps: 0

Alignment:
....
1 MCAERLGQFMTLALVLATFDPARGTDATNPPEGPQDRSSQQKGRLSLQNT 50
||||||||||||||||||||||||||||||||||||||||
1 MCAERLGQFMTLALVLATFDPARGTDATNPPEGPQDRSSQQKGRLSLQNT 50
....
51 AEIQHCLVNAGDVGCGVFECFENNSCEIRGLHGICMMTFLHNAGGFDAQGK 100
||||||||||||||||||||||||||||||||||||||||
51 AEIQHCLVNAGDVGCGVFECFENNSCEIRGLHGICMMTFLHNAGGFDAQGK 100
....
101 SFIKDALKCKAHALRHRFGCISRKCPAIREMVSQLQRECYLKHDLCAAAQ 150
||||||||||||||||||||||||||||||||||||||||
101 SFIKDALKCKAHALRHRFGCISRKCPAIREMVSQLQRECYLKHDLCAAAQ 150
.
151 ENTRVIVEMIHFKDLLLHECY 171
||||||||||||||||||
151 ENTRVIVEMIHFKDLLLHEPY 171

Description of Cluster R38144 Cluster R38144 is characterized by 6 transcripts and 24 segments of interest, the names of which are shown in Tables 1169 and 1170, respectively, and the sequence itself is shown at the end of the application. Selected protein variants are shown in Table 1171.

  These sequences are the putative α-mannosidase C20 or f31 precursor, which is a known protein, previously known herein as a protein (SwissProt accession identifier CT31_HUMAN, also known as synonym EC3.2.1) (also known as EC3.2.1) It is a variant of SEQ ID NO: 1459).

  The sequence of the protein putative α-mannosidase C20 or f31 precursor is shown at the end of the application as “the putative α-mannosidase C20 or f31 precursor amino acid sequence”. Known polymorphisms of this sequence are shown in Table 1172.

  Localization of the protein putative α-mannosidase C20 or f31 precursor is considered secretion (possibility).

  The following GO annotation applies to previously known proteins. The following annotations have been found: Mannosyl-Oligosaccharides 1 which act on carbohydrate metabolism, N-linked glycosylation, annotation related to molecular function, which are annotations related to biological processes, glycosyl bonds 1 , 2-α-mannosidase, calcium binding, hydrolase, membranes that are annotations related to cellular components.

  GO assignments can be made at one or more http: // www. expasy. SwissProt / TremBl Protein knowledgebase available from ch / sprot / or http: // www. ncbi. nlm. nih. Depends on Locuslink available from gov / projects / LocusLink /.

  Cluster R38144 can be used as a diagnostic marker by overexpression of transcripts of this cluster in cancer. The expression of such transcripts in normal tissues is also shown by the method previously described. The term “number” in the right column of the table and the number on the y-axis of FIG. 45 refer to the weighted expression of ESTs in each category as “ppm” (for ESTs of a particular cluster in this category by ppm Ratio of expression to expression of all ESTs).

  As shown generally for the histograms in FIG. 45 and Table 1173, the following results were obtained. This cluster was overexpressed (at least at minimal levels) in the following pathological conditions: epithelial malignancy, lung malignancy, skin malignancy and gastric cancer.

  As mentioned above, cluster R38144 is characterized by the six transcripts listed in Table 1 above. These transcripts encode proteins which are variants of the protein putative α-mannosidase C20 or f31 precursor. A description of each mutein of the invention is provided herein.

  The mutein R38144_PEA_2_P6 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript R38144_PEA_2_T6. An alignment to a known protein (the putative α-mannosidase C20 or f31 precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between R38144_PEA_2_P6 and CT31_HUMAN 1. Corresponding to amino acids 1 to 412 of CT31_HUMAN, corresponding to amino acids 1 to 412 of R38144_PEA_2_P6 MPFRLLIPLGLLCALLPQHHGAPGPDGSAPDPAHYRERVKAMFYHAYDSYLENAFPFDELRPLTCDGHDTWGSFSLTLIDALDTLLILGNVSEFQRVVEVLQDSVDFDIDVNASVFETNIRVVGGLLSAHLLSKKAGVEVEAGWPCSGPLLRMAEEAARKLLPAFQTPTGMPYGTVNLLHGVNPGETPVTCTAGIGTFIVEFATLSSLTGDPVFEDVARVALMRLWESRSDIGLVGNHIDVLTGKWVAQDAGIGAGVDSYFEYLVKGAILLQDKKLM A part of the main part of the J ア ミ ノ 酸 相同 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も 90 90 90 90 90 90 90 90 90 90 90 90 90 90 38 38 38 38 38 38 38 38 38 90 90 90 90 90 90 90 38 38 38 38 38 38 38 38 38 38 38 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も 少 な く と も? Comprises a second amino acid sequence which is at least 90%, most preferably at least 95% homologous, said first amino acid sequence Acid sequence and a second amino acid sequence, contiguous and in sequential order, the isolated chimeric polypeptide coding R38144_PEA_2_P6.

  2. R38144_PEA_2_P6 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence LASFSHMSDQRSARPQ AGQPHGVVLPGRDCEIPLPPV in R38144_PEA_2_P6 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein R38144_PEA_2_P6 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows SNPs as shown in Table 1175) It indicates whether it is known and the presence of a known SNP in the mutein R38144_PEA_2_P6 sequence supports the putative sequence of this mutein of the invention).

  The glycosylation sites of the mutant protein R38144_PEA_2_P6 compared to the known protein putative α-mannosidase C20 or f31 precursor are shown in Table 1176 (showing its position on the amino acid sequence in the first column, the second column a glycosylation site Indicates whether or not is present in the mutein, and the last column indicates whether this position is different on the mutein).

  The mutein R38144_PEA_2_P6 is encoded by the following transcript: R38144_PEA_2_T6 (sequences shown at the end of the application). The coding part of the transcript R38144_PEA_2_T6 is shown in bold, starting from position 91 and ending at position 1437. The transcript also has the following SNPs listed in Table 1177 (showing its position on the nucleotide sequence and listing another nucleic acid, the last column shows whether the SNP is known, mutein R38144_PEA_2_P6 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein R38144_PEA_2_P13 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript R38144_PEA_2_T13. An alignment to a known protein (the putative α-mannosidase C20 or f31 precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between R38144_PEA_2_P13 and CT31_HUMAN 1. Corresponding to amino acids 1 to 323 of CT31_HUMAN, corresponding to amino acids 1 to 323 of R38144_PEA_2_P13 MPFRLLIPLGLLCALLPQHHGAPGPDGSAPDPAHYRERVKAMFYHAYDSYLENAFPFDELRPLTCDGHDTWGSFSLTLIDALDTLLILGNVSEFQRVVEVLQDSVDFDIDVNASVFETNIRVVGGLLSAHLLSKKAGVEVEAGWPCSGPLLRMAEEAARKLLPAFQTPTGMPYGTVNLLHGVNPGETPVTCTAGIGTFIVEFATLSSLTGDPVFEDVARVALMRLWESRSDIGLVGNHIDVLTGKWVAQDAGIGAGVDSYFEYLVKGAILLQDKKL AMFLEYNKAIRNYTRFDDWYLWVQMYKGTVSMPVFQSLEAYWPGLQ At least 70%, preferably at least 80%, preferably at least 85%, more preferably a polypeptide having the first amino acid sequence at least 90% homologous to the sequence NLLKAQCTSTVPRGIPPS corresponding to amino acids 324 to 341 of R38144_PEA_2_P13, preferably at least 85%, more preferably Comprises R38144_PEA_2_P13, which comprises a second amino acid sequence which is at least 90%, most preferably at least 95% homologous, said first amino acid sequence and the second amino acid sequence being adjacent and in consecutive order Isolated chimeric polypeptide.

  2. R38144_PEA_2_P13 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence NLLKAQCTSTVPRGIPPS in R38144_PEA_2_P13 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein R38144_PEA_2_P13 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows SNPs as shown in Table 1178) It indicates whether it is known and the presence of a known SNP in the mutant protein R38144_PEA_2_P13 sequence supports the deduced sequence of this mutant protein according to the invention).

  The glycosylation sites of the mutated protein R38144_PEA_2_P13 compared to the known protein putative α-mannosidase C20 or f31 precursor are shown in Table 1179 (showing its position on the amino acid sequence in the first column, the second column a glycosylation site Indicates whether or not is present in the mutein, and the last column indicates whether this position is different on the mutein).

  The mutein R38144_PEA_2_P13 is encoded by the following transcript: R38144_PEA_2_T13 (sequences shown at the end of the application). The coding part of the transcript R38144_PEA_2_T13 is shown in bold, starting from position 91 and ending at position 1113. The transcript also has the following SNPs listed in Table 1180 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein R38144_PEA_2_P13 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein R38144_PEA_2_P15 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript R38144_PEA_2_T15. An alignment to a known protein (the putative α-mannosidase C20 or f31 precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between R38144_PEA_2_P15 and CT31_HUMAN 1. Corresponding to amino acids 1 to 282 of CT31_HUMAN, corresponding to amino acids 1 to 282 of R38144_PEA_2_P15 MPFRLLIPLGLLCALLPQHHGAPGPDGSAPDPAHYRERVKAMFYHAYDSYLENAFPFDELRPLTCDGHDTWGSFSLTLIDALDTLLILGNVSEFQRVVEVLQDSVDFDIDVNASVFETNIRVVGGLLSAHLLSKKAGVEVEAGWPCSGPLLRMAEEAARKLLPAFQTPTGMPYGTVNLLHGVNPGETPVTCTAGIGTFIVEFATLSSLTGDPVFEDVARVALMRLWESRSDIGLVGNHIDVLTGKWVAQDAGIGAGVDSYFEYLVKGAILLQDKKL A polypeptide having a first amino acid sequence at least 90% homologous to AMFLE and a sequence PHWRH corresponding to amino acids 283-287 of R38144_PEA_2_P15, at least 70%, optionally at least 80%, preferably at least 85%, more preferably Comprises R38144_PEA_2_P15, which comprises a second amino acid sequence which is at least 90%, most preferably at least 95% homologous, said first amino acid sequence and the second amino acid sequence being adjacent and in sequential order Isolated chimeric polypeptide.

  2. R38144_PEA_2_P15 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence PHWRH in R38144_PEA_2_P15 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein R38144_PEA_2_P15 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows SNPs as shown in Table 1181) It indicates whether it is known and the presence of a known SNP in the mutant protein R38144_PEA_2_P15 sequence supports the deduced sequence of this mutant protein according to the invention).

  The glycosylation sites of the mutant protein R38144_PEA_2_P15 compared to the known protein putative α-mannosidase C20 or f31 precursor are shown in Table 1182 (showing its position on the amino acid sequence in the first column, the second column a glycosylation site Indicates whether or not is present in the mutein, and the last column indicates whether this position is different on the mutein).

  The mutein R38144_PEA_2_P15 is encoded by the following transcript: R38144_PEA_2_T15 (sequences shown at the end of the application). The coding part of the transcript R38144_PEA_2_T15 is shown in bold, starting from position 91 and ending at position 951. The transcript also has the following SNPs listed in Table 1183 (showing its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein R38144_PEA_2_P15 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein R38144_PEA_2_P19 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript R38144_PEA_2_T19. An alignment to a known protein (the putative α-mannosidase C20 or f31 precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between R38144_PEA_2_P19 and CT31_HUMAN 1. Corresponding to amino acids 1 to 412 of CT31_HUMAN, corresponding to amino acids 1 to 412 of R38144_PEA_2_P19 MPFRLLIPLGLLCALLPQHHGAPGPDGSAPDPAHYRERVKAMFYHAYDSYLENAFPFDELRPLTCDGHDTWGSFSLTLIDALDTLLILGNVSEFQRVVEVLQDSVDFDIDVNASVFETNIRVVGGLLSAHLLSKKAGVEVEAGWPCSGPLLRMAEEAARKLLPAFQTPTGMPYGTVNLLHGVNPGETPVTCTAGIGTFIVEFATLSSLTGDPVFEDVARVALMRLWESRSDIGLVGNHIDVLTGKWVAQDAGIGAGVDSYFEYLVKGAILLQDKKL AMFLEYNKAIRNYTRFDDWYLWVQMYKGTVSMPVFQSLEAYWPGLQSLIGIDIDNAMRFLTNYTVWKQFGGLPEFYNIPQGYTVEK YELG ELPEL IE SAMYLYRATDGPTTLLEGRDAVES HEKHI 1 少 な く と も 433 ア ミ ノ 酸 ア ミ ノ 酸 ア ミ ノ 酸 ア ミ ノ 酸 ア ミ ノ 酸 ア ミ ノ 酸 ア ミ ノ 酸 ア ミ ノ 酸 ア ミ ノ 酸 ア ミ ノ 酸 ア ミ ノ 酸 ア ミ ノ 酸 ア ミ ノ 酸 ア ミ ノ 酸 ア ミ ノ 酸 ア ミ ノ 酸 ア ミ ノ 酸 ア ミ ノ 酸 ア ミ ノ 酸Comprises a second amino acid sequence which is at least 90%, most preferably at least 95% homologous, said first amino acid sequence and said second amino acid Columns, adjacent and in sequential order, the isolated chimeric polypeptide coding R38144_PEA_2_P19.

  2. R38144_PEA_2_P19 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence KRSRSVAQAGVQWCDHDSPQ in R38144_PEA_2_P19 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein R38144_PEA_2_P19 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows SNPs as shown in Table 1184) It indicates whether it is known and the presence of a known SNP in the mutant protein R38144_PEA_2_P19 sequence supports the deduced sequence of this mutant protein according to the invention).

  The glycosylation sites of the mutant protein R38144_PEA_2_P19 compared to the known protein putative α-mannosidase C20 or f31 precursor are shown in Table 1185 (showing its position on the amino acid sequence in the first column, the second column a glycosylation site Indicates whether or not is present in the mutein, and the last column indicates whether this position is different on the mutein).

  The mutein R38144_PEA_2_P19 is encoded by the following transcript: R38144_PEA_2_T19 (sequences shown at the end of the application). The coding part of the transcript R38144_PEA_2_T19 is shown in bold, starting from position 91 and ending at position 1389. The transcript also has the following SNPs listed in Table 1186 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein R38144_PEA_2_P19 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein R38144_PEA_2_P24 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript R38144_PEA_2_T27. An alignment to a known protein (the putative α-mannosidase C20 or f31 precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between R38144_PEA_2_P24 and CT31_HUMAN 1. Corresponding to amino acids 1 to 121 of CT31_HUMAN, first amino acid sequence at least 90% homologous to the corresponding MPFRLLIPLGLLCALLPQHHGAPGPDGSAPDPAHYRERVKAMFYHAYDSYLENAFPFDELRPLTCDGHDTWGSFSLTLIDALDTLLILGNVSEFQRVVEVLQDSVDFDIDVNASVFETNIR to amino acids 1 to 121 of R38144_PEA_2_P24, corresponding to amino acids 282-578 of CT31_HUMAN sequence EYNKAIRNYTRFDDWYLWVQMYKGTVSMPVFQSLEAYWPGLQSLIGDIDNAMRTFLNYYTVWKQFGGLPEFYNIPQGYTVEKREGYPLRPELIESAMYLYRAT DPTLLELGRDAVESIEKISKVECGFATIKDLRDHKLDNRMESFFLAETVKYLYLLFDPTNFIHNNGSTFDAVITPYGECILGAGGYIFNTEAHPIDPAALHCCQRLKEEQWEVEDLMREFYSLKRSRSKFQKNTVSSGPWEPPARPGTLFSPENHDQARERKPAKQKVPLLSCPSQPFTSKLALLGQVFLDSS and and at least 90% homologous to a second amino acid sequence, the first amino acid sequence and a second amino acid sequence, contiguous and in sequential order, the isolated chimeric polypeptide encoding R38144_PEA_2_P24 .

  2. Length “n” (wherein n is at least about 10 amino acids long, optionally at least about 20 amino acids long, preferably at least about 30 amino acids long, more preferably at least about 40 amino acids long, most preferably at least about 50 amino acids long, at least two amino acids comprising RE, starting from any of the following structures: amino acid numbers 121-x to 121, amino acid numbers 122 + ((n-2) -x) (formula An isolated chimeric polypeptide encoding an edge portion of R38144_PEA_2_P24, comprising a polypeptide, having a sequence terminating in :), wherein x is a change from 0 to n-2.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein R38144_PEA_2_P24 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows SNPs as shown in Table 1187) It indicates whether it is known and the presence of a known SNP in the mutant protein R38144_PEA_2_P24 sequence supports the deduced sequence of this mutant protein according to the invention).

  The glycosylation sites of the mutant protein R38144_PEA_2_P24 compared to the known protein putative α-mannosidase C20orf31 precursor are shown in Table 1188 (showing its position on the amino acid sequence in the first column, the second column a glycosylation site Indicates whether or not is present in the mutein, and the last column indicates whether this position is different on the mutein).

  The mutein R38144_PEA_2_P24 is encoded by the following transcript: R38144_PEA_2_T27 (sequences shown at the end of the application). The code portion of the transcript R38144_PEA_2_T27 is shown in bold, starting from position 91 and ending at position 1344. The transcript also has the following SNPs listed in Table 1189 (showing its position on the nucleotide sequence, listing another nucleic acid, the last column shows whether the SNP is known, mutein R38144_PEA_2_P24 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein R38144_PEA_2_P36 of the present invention has the amino acid sequence shown at the end of the application and is encoded by the transcript R38144_PEA_2_T10. An alignment to a known protein (presumed α-mannosidase C20 or f31 precursor, SEQ ID NO: 1459) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between R38144_PEA_2_P36 and AAH 16184 (SEQ ID NO: 1460) A polypeptide having a first amino acid sequence corresponding to amino acids 1 to 36 of AAH 16184 and corresponding to amino acids 1 to 36 of R38144_PEA_2_P36 and MPFRLLIPLGLLCALLPQHHGAPGPDGSAPSAPAPHYR and the sequence FWGMSQNSKEWLKCRTTAWTLILM corresponding to amino acids 37 to 60 of R38144_PEA_2_P36 Said second amino acid sequence comprising a second amino acid sequence which is at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous; An isolated fragment encoding R38144_PEA_2_P36, wherein the two amino acid sequences are in contiguous and sequential order Polypeptide.

  2. R38144_PEA_2_P36 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence FWGMSQNSKEWLKCSRTAWTL in R38144_PEA_2_P36 An isolated polypeptide encoding a tail.

Report on comparison between R38144_PEA_2_P36 and AAQ 88943 (SEQ ID NO: 1461) A polypeptide having a first amino acid sequence corresponding to amino acids 1 to 35 of AAQ 88943 and corresponding to amino acids 1 to 35 of R38144_PEA_2_P36 and MPFRLLIPLGLLCALLPQHHGAPGPDGSAPSAPAPHY and the sequence RFWGMSQNSKEWLCSRTAWTLM corresponding to amino acids 36 to 60 of R38144_PEA_2_P36 Said second amino acid sequence comprising a second amino acid sequence which is at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous; An isolated fragment encoding R38144_PEA_2_P36, wherein the two amino acid sequences are in contiguous and sequential order Polypeptide.

  2. R38144_PEA_2_P36 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence RFWGMSQ NSKEWLKCSRTAWTL in R38144_PEA_2_P36 An isolated polypeptide encoding a tail.

Report of comparison between R38144_PEA_2_P36 and CT31_HUMAN 1. A polypeptide having a first amino acid sequence corresponding to amino acids 1-36 of CT31_HUMAN and corresponding to amino acids 1-36 of R38144_PEA_2_P36 with MPFRLLIPLGLLCALLPQHHGAPGPDGSAPSAPAPHYR and the sequence FWGMSQNSKEWLCKCRTTAWTLM corresponding to amino acids 37-60 of R38144_PEA_2_P36 Said second amino acid sequence comprising a second amino acid sequence which is at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous; Isolation encoding R38144_PEA_2_P36, wherein the two amino acid sequences are in contiguous and sequential order Mera polypeptide.

  2. R38144_PEA_2_P36 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence FWGMSQNSKEWLKCSRTAWTL in R38144_PEA_2_P36 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein R38144_PEA_2_P36 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows SNPs as shown in Table 1190) It indicates whether it is known and the presence of a known SNP in the mutant protein R38144_PEA_2_P36 sequence supports the predicted sequence of this mutant protein according to the invention).

  The glycosylation sites of the mutant protein R38144_PEA_2_P36 compared to the known protein putative α-mannosidase C20orf31 precursor are shown in Table 1191 (showing its position on the amino acid sequence in the first column, the second column a glycosylation site Indicates whether or not is present in the mutein, and the last column indicates whether this position is different on the mutein).

  The mutein R38144_PEA_2_P36 is encoded by the following transcript: R38144_PEA_2_T10 (sequences shown at the end of the application). The code portion of transcript R38144_PEA_2_T10 is shown in bold, starting at position 91 and ending at position 270. The transcript also has the following SNPs listed in Table 1192 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein R38144_PEA_2_P36 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  As mentioned above, cluster R38144 is characterized by the 24 segments listed in Table 2 above, the sequence of which is shown at the end of the application. These segments are part of the nucleic acid sequence, which are of particular interest and are individually described herein. A description of each segment of the invention is provided herein.

  The segment cluster R38144_PEA_2_node_21 of the present invention is supported by 108 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: R38144_PEA_2_T6, R38144_PEA_2_T10, R38144_PEA_2_T13, R38144_PEA_2_T15, and R38144_PEA_2_T19. Table 1193 below describes the start and end positions of this segment on each transcript.

  The segment cluster R38144_PEA_2_node_26 of the present invention is supported by 98 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: R38144_PEA_2_T6, R38144_PEA_2_T10, R38144_PEA_2_T13, R38144_PEA_2_T15, and R38144_PEA_2_T19. Table 1194 below describes the start and end positions of this segment on each transcript.

  The segment cluster R38144_PEA_2_node_29 of the present invention is supported by 98 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: R38144_PEA_2_T6, R38144_PEA_2_T10, R38144_PEA_2_T13, R38144_PEA_2_T19, and R38144_PEA_2_T27. Table 1195 below describes the start and end positions of this segment on each transcript.

  The segment cluster R38144_PEA_2_node_31 of the present invention is supported by 95 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: R38144_PEA_2_T6, R38144_PEA_2_T10, R38144_PEA_2_T15, R38144_PEA_2_T19, and R38144_PEA_2_T27. Table 1196 below describes the start and end positions of this segment on each transcript.

  The segment cluster R38144_PEA_2_node_46 of the present invention is supported by 147 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: R38144_PEA_2_T6, R38144_PEA_2_T10, R38144_PEA_2_T13, R38144_PEA_2_T15, and R38144_PEA_2_T27. Table 1197 below describes the start and end positions of this segment on each transcript.

  The segment cluster R38144_PEA_2_node_47 of the present invention is supported by 147 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: R38144_PEA_2_T6, R38144_PEA_2_T10, R38144_PEA_2_T13, R38144_PEA_2_T15, and R38144_PEA_2_T27. Table 1198 below describes the start and end positions of this segment on each transcript.

  The segment cluster R38144_PEA_2_node_49 of the present invention is supported by one library. The number of libraries was determined as described above. This segment can be found in the following transcript: R38144_PEA_2_T19. Table 1199 below describes the start and end positions of this segment on each transcript.

  According to an optional embodiment of the present invention, there is also provided a short segment associated with the above cluster. These segments are up to about 120 bp in length and are therefore included in the individual descriptions.

  The segment cluster R38144_PEA_2_node_0 of the present invention is supported by 101 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: R38144_PEA_2_T6, R38144_PEA_2_T10, R38144_PEA_2_T13, R38144_PEA_2_T15, R38144_PEA_2_T19, and R38144_PEA_2_T27. Table 1200 below describes the start and end positions of this segment on each transcript.

  The segment cluster R38144_PEA_2_node_1 of the present invention is supported by 105 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: R38144_PEA_2_T6, R38144_PEA_2_T10, R38144_PEA_2_T13, R38144_PEA_2_T15, R38144_PEA_2_T19, and R38144_PEA_2_T27. Table 1202 below describes the start and end positions of this segment on each transcript.

  The segment cluster R38144_PEA_2_node_4 of the present invention is supported by 107 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: R38144_PEA_2_T6, R38144_PEA_2_T13, R38144_PEA_2_T15, R38144_PEA_2_T19, and R38144_PEA_2_T27. Table 1203 below describes the start and end positions of this segment on each transcript.

  The segment cluster R38144_PEA_2_node_5 of the invention can be found in the following transcripts: R38144_PEA_2_T6, R38144_PEA_2_T13, R38144_PEA_2_T15, R38144_PEA_2_T19, and R38144_PEA_2_T27. Table 1204 below describes the start and end positions of this segment on each transcript.

  The segment cluster R38144_PEA_2_node_7 of the present invention is supported by 92 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: R38144_PEA_2_T6, R38144_PEA_2_T13, R38144_PEA_2_T15, R38144_PEA_2_T19, and R38144_PEA_2_T27. Table 1205 below describes the start and end positions of this segment on each transcript.

  The segment cluster R38144_PEA_2_node_11 of the present invention is supported by 106 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: R38144_PEA_2_T6, R38144_PEA_2_T10, R38144_PEA_2_T13, R38144_PEA_2_T15, R38144_PEA_2_T19, and R38144_PEA_2_T27. Table 1206 below describes the start and end positions of this segment on each transcript.

  The segment cluster R38144_PEA_2_node_14 according to the invention can be found in the following transcripts: R38144_PEA_2_T6, R38144_PEA_2_T10, R38144_PEA_2_T13, R38144_PEA_2_T15, and R38144_PEA_2_T19. Table 1207 below describes the start and end positions of this segment on each transcript.

  The segment cluster R38144_PEA_2_node_15 of the present invention is supported by 105 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: R38144_PEA_2_T6, R38144_PEA_2_T10, R38144_PEA_2_T13, R38144_PEA_2_T15, and R38144_PEA_2_T19. Table 1208 below describes the start and end positions of this segment on each transcript.

  The segment cluster R38144_PEA_2_node_16 of the present invention is supported by 106 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: R38144_PEA_2_T6, R38144_PEA_2_T10, R38144_PEA_2_T13, R38144_PEA_2_T15, and R38144_PEA_2_T19. Table 1209 below describes the start and end positions of this segment on each transcript.

  The segment cluster R38144_PEA_2_node_19 of the present invention is supported by 93 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: R38144_PEA_2_T6, R38144_PEA_2_T10, R38144_PEA_2_T13, R38144_PEA_2_T15, and R38144_PEA_2_T19. Table 1210 below describes the start and end positions of this segment on each transcript.

  The segment cluster R38144_PEA_2_node_20 according to the invention can be found in the following transcripts: R38144_PEA_2_T6, R38144_PEA_2_T10, R38144_PEA_2_T13, R38144_PEA_2_T15, and R38144_PEA_2_T19. Table 1211 below describes the start and end positions of this segment on each transcript.

  The segment cluster R38144_PEA_2_node_36 of the present invention is supported by 95 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: R38144_PEA_2_T6, R38144_PEA_2_T10, R38144_PEA_2_T13, R38144_PEA_2_T15, R38144_PEA_2_T19, and R38144_PEA_2_T27. Table 1212 below describes the start and end positions of this segment on each transcript.

  The segment cluster R38144_PEA_2_node_37 of the present invention is supported by 97 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: R38144_PEA_2_T6, R38144_PEA_2_T10, R38144_PEA_2_T13, R38144_PEA_2_T15, R38144_PEA_2_T19, and R38144_PEA_2_T27. Table 1213 below describes the start and end positions of this segment on each transcript.

  The segment cluster R38144_PEA_2_node_43 according to the invention can be found in the following transcript: R38144_PEA_2_T6. Table 1214 below describes the start and end positions of this segment on each transcript.

  The segment cluster R38144_PEA_2_node_44 according to the invention can be found in the following transcript: R38144_PEA_2_T6. Table 1215 below describes the start and end positions of this segment on each transcript.

  The segment cluster R38144_PEA_2_node_45 according to the invention can be found in the following transcripts: R38144_PEA_2_T6, R38144_PEA_2_T10, R38144_PEA_2_T13, R38144_PEA_2_T15, and R38144_PEA_2_T27. Table 1216 below describes the start and end positions of this segment on each transcript.

  The segment cluster R38144_PEA_2_node_51 of the present invention is supported by one library. The number of libraries was determined as described above. This segment can be found in the following transcript: R38144_PEA_2_T19. Table 1217 below describes the start and end positions of this segment on each transcript.

Mutated protein alignment against previously known proteins:
Sequence name: CT31_HUMAN

Sequence documentation:

Alignment of: R38144_PEA_2_P6 x CT31_HUMAN ..

Alignment segment 1/1:

Quality: 4031.00 Escore: 0
Matching length: 413 Total length: 413
Matching Percent Similarity: 100.00 Matching Percent Identity: 99.76
Total Percent Similarity: 100.00 Total Percent Identity: 99.76
Gaps: 0

Alignment:
....
1 MPFRLLIPLGLLCALLPQHHGAPGPDGSAPSAPADAHYREVKAMFYHAYDSY 50
||||||||||||||||||||||||||||||||||||||||
1 MPFRLLIPLGLLCALLPQHHGAPGPDGSAPSAPADAHYREVKAMFYHAYDSY 50
....
51 LENAFPFDELRPLTCDDGHDTWSFSFSLTLIDALDTLLILGNVSEFQRVVEV 100
||||||||||||||||||||||||||||||||||||||||
51 LENAFPFDELRPLTCDDGHDTWSFSFSLTLIDALDTLLILGNVSEFQRVVEV 100
....
101 LQDSVFDFDIDVNASVFETNIRVVGGLLSHLLSKKAGVEVEAGWPCSGPL 150
||||||||||||||||||||||||||||||||||||||||
101 LQDSVFDFDIDVNASVFETNIRVVGGLLSHLLSKKAGVEVEAGWPCSGPL 150
....
151 LRM AEEA ARKL LP AF Q TP GM Y GT V N LL H HG V NP GET PVTC TAG IG TF IV 200
||||||||||||||||||||||||||||||||||||||||
151 LRM AEEA ARKL LP AF Q TP GM Y GT V N LL H HG V NP GET PVTC TAG IG TF IV 200
....
201 EFATLSSLTGDPFVED VARVALMRWESSDIGLVGNHID VLTGKWVAQD 250
||||||||||||||||||||||||||||||||||||||||
201 EFATLSSLTGDPFVED VARVALMRWESSDIGLVGNHID VLTGKWVAQD 250
....
251 AGIGAGVDSYFEYLVKGAILLQDKKLMAMFLEYNKAIRNYTRFDDWYLWV 300
||||||||||||||||||||||||||||||||||||||||
251 AGIGAGVDSYFEYLVKGAILLQDKKLMAMFLEYNKAIRNYTRFDDWYLWV 300
....
301 QMYKGTVSMPVFQSLEAYWPGLQSLIGDIDNAMMRTLNYYTVWKQFGFLP 350
||||||||||||||||||||||||||||||||||||||||
301 QMYKGTVSMPVFQSLEAYWPGLQSLIGDIDNAMMRTLNYYTVWKQFGFLP 350
....
351 EFYNIPQGYTVEKREGYPLRPELIESAMYLYRATDGPTLELGRDAVESI 400
||||||||||||||||||||||||||||||||||||||||
351 EFYNIPQGYTVEKREGYPLRPELIESAMYLYRATDGPTLELGRDAVESI 400
.
401 EKISK VECGFATL 413
||||||||||: |
401 EKISKVECGFATI 413






Sequence name: CT31_HUMAN

Sequence documentation:

Alignment of: R38144_PEA_2_P13 x CT31_HUMAN ..

Alignment segment 1/1:

Quality: 3167.00 Escore: 0
Matching length: 326 Total length: 326
Matching Percent Similarity: 100.00 Matching Percent Identity: 99.39
Total Percent Similarity: 100.00 Total Percent Identity: 99.39
Gaps: 0

Alignment:
....
1 MPFRLLIPLGLLCALLPQHHGAPGPDGSAPSAPADAHYREVKAMFYHAYDSY 50
||||||||||||||||||||||||||||||||||||||||
1 MPFRLLIPLGLLCALLPQHHGAPGPDGSAPSAPADAHYREVKAMFYHAYDSY 50
....
51 LENAFPFDELRPLTCDDGHDTWSFSFSLTLIDALDTLLILGNVSEFQRVVEV 100
||||||||||||||||||||||||||||||||||||||||
51 LENAFPFDELRPLTCDDGHDTWSFSFSLTLIDALDTLLILGNVSEFQRVVEV 100
....
101 LQDSVFDFDIDVNASVFETNIRVVGGLLSHLLSKKAGVEVEAGWPCSGPL 150
||||||||||||||||||||||||||||||||||||||||
101 LQDSVFDFDIDVNASVFETNIRVVGGLLSHLLSKKAGVEVEAGWPCSGPL 150
....
151 LRM AEEA ARKL LP AF Q TP GM Y GT V N LL H HG V NP GET PVTC TAG IG TF IV 200
||||||||||||||||||||||||||||||||||||||||
151 LRM AEEA ARKL LP AF Q TP GM Y GT V N LL H HG V NP GET PVTC TAG IG TF IV 200
....
201 EFATLSSLTGDPFVED VARVALMRWESSDIGLVGNHID VLTGKWVAQD 250
||||||||||||||||||||||||||||||||||||||||
201 EFATLSSLTGDPFVED VARVALMRWESSDIGLVGNHID VLTGKWVAQD 250
....
251 AGIGAGVDSYFEYLVKGAILLQDKKLMAMFLEYNKAIRNYTRFDDWYLWV 300
||||||||||||||||||||||||||||||||||||||||
251 AGIGAGVDSYFEYLVKGAILLQDKKLMAMFLEYNKAIRNYTRFDDWYLWV 300
.
301 QMYKGTVSMPVFQSLEAYWPGLQNLL 326
||||||||||||||||||||: |
301 QMYKGTVSMPVFQSLEAYWPGLQSLI 326






Sequence name: CT31_HUMAN

Sequence documentation:

Alignment of: R38144_PEA_2_P15 x CT31_HUMAN ..

Alignment segment 1/1:

Quality: 2725.00 Escore: 0
Matching length: 282 Total length: 282
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MPFRLLIPLGLLCALLPQHHGAPGPDGSAPSAPADAHYREVKAMFYHAYDSY 50
||||||||||||||||||||||||||||||||||||||||
1 MPFRLLIPLGLLCALLPQHHGAPGPDGSAPSAPADAHYREVKAMFYHAYDSY 50
....
51 LENAFPFDELRPLTCDDGHDTWSFSFSLTLIDALDTLLILGNVSEFQRVVEV 100
||||||||||||||||||||||||||||||||||||||||
51 LENAFPFDELRPLTCDDGHDTWSFSFSLTLIDALDTLLILGNVSEFQRVVEV 100
....
101 LQDSVFDFDIDVNASVFETNIRVVGGLLSHLLSKKAGVEVEAGWPCSGPL 150
||||||||||||||||||||||||||||||||||||||||
101 LQDSVFDFDIDVNASVFETNIRVVGGLLSHLLSKKAGVEVEAGWPCSGPL 150
....
151 LRM AEEA ARKL LP AF Q TP GM Y GT V N LL H HG V NP GET PVTC TAG IG TF IV 200
||||||||||||||||||||||||||||||||||||||||
151 LRM AEEA ARKL LP AF Q TP GM Y GT V N LL H HG V NP GET PVTC TAG IG TF IV 200
....
201 EFATLSSLTGDPFVED VARVALMRWESSDIGLVGNHID VLTGKWVAQD 250
||||||||||||||||||||||||||||||||||||||||
201 EFATLSSLTGDPFVED VARVALMRWESSDIGLVGNHID VLTGKWVAQD 250
....
251 AGIGAGVDSYFEYLVKGAILLQDKKLMAMFLE 282
||||||||||||||||||||||||||||||
251 AGIGAGVDSYFEYLVKGAILLQDKKLMAMFLE 282






Sequence name: CT31_HUMAN

Sequence documentation:

Alignment of: R38144_PEA_2_P19 x CT31_HUMAN ..

Alignment segment 1/1:

Quality: 4029.00 Escore: 0
Matching length: 412 Total length: 412
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MPFRLLIPLGLLCALLPQHHGAPGPDGSAPSAPADAHYREVKAMFYHAYDSY 50
||||||||||||||||||||||||||||||||||||||||
1 MPFRLLIPLGLLCALLPQHHGAPGPDGSAPSAPADAHYREVKAMFYHAYDSY 50
....
51 LENAFPFDELRPLTCDDGHDTWSFSFSLTLIDALDTLLILGNVSEFQRVVEV 100
||||||||||||||||||||||||||||||||||||||||
51 LENAFPFDELRPLTCDDGHDTWSFSFSLTLIDALDTLLILGNVSEFQRVVEV 100
....
101 LQDSVFDFDIDVNASVFETNIRVVGGLLSHLLSKKAGVEVEAGWPCSGPL 150
||||||||||||||||||||||||||||||||||||||||
101 LQDSVFDFDIDVNASVFETNIRVVGGLLSHLLSKKAGVEVEAGWPCSGPL 150
....
151 LRM AEEA ARKL LP AF Q TP GM Y GT V N LL H HG V NP GET PVTC TAG IG TF IV 200
||||||||||||||||||||||||||||||||||||||||
151 LRM AEEA ARKL LP AF Q TP GM Y GT V N LL H HG V NP GET PVTC TAG IG TF IV 200
....
201 EFATLSSLTGDPFVED VARVALMRWESSDIGLVGNHID VLTGKWVAQD 250
||||||||||||||||||||||||||||||||||||||||
201 EFATLSSLTGDPFVED VARVALMRWESSDIGLVGNHID VLTGKWVAQD 250
....
251 AGIGAGVDSYFEYLVKGAILLQDKKLMAMFLEYNKAIRNYTRFDDWYLWV 300
||||||||||||||||||||||||||||||||||||||||
251 AGIGAGVDSYFEYLVKGAILLQDKKLMAMFLEYNKAIRNYTRFDDWYLWV 300
....
301 QMYKGTVSMPVFQSLEAYWPGLQSLIGDIDNAMMRTLNYYTVWKQFGFLP 350
||||||||||||||||||||||||||||||||||||||||
301 QMYKGTVSMPVFQSLEAYWPGLQSLIGDIDNAMMRTLNYYTVWKQFGFLP 350
....
351 EFYNIPQGYTVEKREGYPLRPELIESAMYLYRATDGPTLELGRDAVESI 400
||||||||||||||||||||||||||||||||||||||||
351 EFYNIPQGYTVEKREGYPLRPELIESAMYLYRATDGPTLELGRDAVESI 400
.
401 EKISKVECG FAT 412
||||||||||||
401 EKISKVECG FAT 412






Sequence name: CT31_HUMAN

Sequence documentation:

Alignment of: R38144_PEA_2_P24 x CT31_HUMAN ..

Alignment segment 1/1:

Quality: 4063.00 Escore: 0
Matching length: 418 Total length: 578
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 72.32 Total Percent Identity: 72.32
Gaps: 1

Alignment:
....
1 MPFRLLIPLGLLCALLPQHHGAPGPDGSAPSAPADAHYREVKAMFYHAYDSY 50
||||||||||||||||||||||||||||||||||||||||
1 MPFRLLIPLGLLCALLPQHHGAPGPDGSAPSAPADAHYREVKAMFYHAYDSY 50
....
51 LENAFPFDELRPLTCDDGHDTWSFSFSLTLIDALDTLLILGNVSEFQRVVEV 100
||||||||||||||||||||||||||||||||||||||||
51 LENAFPFDELRPLTCDDGHDTWSFSFSLTLIDALDTLLILGNVSEFQRVVEV 100
....
101 LQDSVFDFDIVNASVFETNIR ......................................... 121
||||||||||||||||||||
101 LQDSVFDFDIDVNASVFETNIRVVGGLLSHLLSKKAGVEVEAGWPCSGPL 150
....
121 ...................................................... . 121

151 LRM AEEA ARKL LP AF Q TP GM Y GT V N LL H HG V NP GET PVTC TAG IG TF IV 200
....
121 ...................................................... . 121

201 EFATLSSLTGDPFVED VARVALMRWESSDIGLVGNHID VLTGKWVAQD 250
....
122 ................................... EYNKAIRNYTRFDDWYLWV 140
||||||||||||||||||
251 AGIGAGVDSYFEYLVKGAILLQDKKLMAMFLEYNKAIRNYTRFDDWYLWV 300
....
141 QMYKGTVSMPVFQSLEAYWPGLQSLIGDIDNAMMRTLNYYTVWKQFGGLP 190
||||||||||||||||||||||||||||||||||||||||
301 QMYKGTVSMPVFQSLEAYWPGLQSLIGDIDNAMMRTLNYYTVWKQFGFLP 350
....
191 EFYNIPQGYTVEKREGYPLRPELIESAMYLYRATDGPTLELGRDAVESI 240
||||||||||||||||||||||||||||||||||||||||
351 EFYNIPQGYTVEKREGYPLRPELIESAMYLYRATDGPTLELGRDAVESI 400
....
241 EKISKVECGFATIKDLRDHKLDNRMESFFLAETVKYLYLLFDPTNFIHNN 290
||||||||||||||||||||||||||||||||||||||||
401 EKISKVECGFATIKDLRDHKLDNRMESFFLAETVKYLYLLFDPTNFIHNN 450
....
291 GSTFDAVITPYGECILGAGGYIFNTEAHPIDPAALHCCQRLKEEQWEVED 340
||||||||||||||||||||||||||||||||||||||||
451 GSTFDAVITPYGECILGAGGYIFNTEAHPIDPAALHCCQRLKEEQWEVED 500
....
341 LMREFYSLKRSRSKFQKNTVSSGPWEPPRPGTLFSPENHDQARERKPAK 390
||||||||||||||||||||||||||||||||||||||||
501 LMREFYSLKRSRSKFQKNTVSSGPWEPPRPGTLFSPENHDQARERKPAK 550
.
391 QKVPLLSCPSQPFTSKLALLGQVFLDSS 418
||||||||||||||||||||||||||
551 QKVPLLSCPSQPFTSKLALLGQVFLDSS 578






Sequence name: AAH16184

Sequence documentation:

Alignment of: R38144_PEA_2_P36 x AAH16184 ..

Alignment segment 1/1:

Quality: 364.00 Escore: 0
Matching length: 36 Total length: 36
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MPFRLLIPLGLLCALLPQHHGAPGPDGSAPSAPDAHYR 36
|||||||||||||||||||||||||||||||||
1 MPFRLLIPLGLLCALLPQHHGAPGPDGSAPSAPDAHYR 36






Sequence name: AAQ88943

Sequence documentation:

Alignment of: R38144_PEA_2_P36 x AAQ88943 ..

Alignment segment 1/1:

Quality: 362.00 Escore: 0
Matching length: 37 Total length: 37
Matching Percent Similarity: 97.30 Matching Percent Identity: 97.30
Total Percent Similarity: 97.30 Total Percent Identity: 97.30
Gaps: 0

Alignment:
....
1 MPFRLLIPLGLLCALLPQHHGAPGPDGSAPSAPDAHYRF 37
|||||||||||||||||||||||||||||||
1 MPFRLLIPLGLLCALLPQHHGAPGPDGSAPSAPDAHYSF 37






Sequence name: CT31_HUMAN

Sequence documentation:

Alignment of: R38144_PEA_2_P36 x CT31_HUMAN ..

Alignment segment 1/1:

Quality: 364.00 Escore: 0
Matching length: 36 Total length: 36
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MPFRLLIPLGLLCALLPQHHGAPGPDGSAPSAPDAHYR 36
|||||||||||||||||||||||||||||||||
1 MPFRLLIPLGLLCALLPQHHGAPGPDGSAPSAPDAHYR 36

Description of cluster HUMOSTRO Cluster HUMOSTRO features 3 transcripts of interest and 30 segments, the names of which are given in Tables 1218 and 1219 respectively, and the sequence itself is given at the end of the application. Selected protein variants are shown in Table 1220.

  These sequences are osteopontin precursors (SwissProt accession identifier OSTP_HUMAN, synonym bone sialoprotein 1, urinary calculus protein, secretory phosphoprotein 1, SPP, which is a known protein previously referred to herein as a protein). -1, a variant of Nephropontin, which is also known as uropontin (SEQ ID NO: 1462).

  The protein osteopontin precursor is known or considered to have the following function: it appears to form an integral part of the calcified substrate. Possibly important for cell-substrate interactions. Acts as a cytokine involved in enhancing interferon-gamma and interleukin-12 production as well as reducing interleukin-10 production and is essential for pathways that result in type I immunity (by similarity). The sequence of the protein osteopontin precursor is shown at the end of the application as "osteopontin precursor amino acid sequence". Known polymorphisms of this sequence are shown in Table 1221.

  Localization of the protein osteopontin precursor is considered secretion.

  The previously known proteins also have the following indications and / or potential therapeutic applications: Regeneration (bone). Clinical / therapeutic applications in humans (e.g. as targets for antibodies or small molecules and / or as direct therapy) are being investigated and available information related to these investigations is: Potential pharmaceutically relevant or therapeutically relevant activities of previously known proteins are: bone formation stimulants. The therapeutic role of proteins displayed by clusters is expected. Because information is present in drug databases or public databases (eg, above) that may or may not be used to apply (musculoskeletal) this protein or portions thereof for potential treatment, clusters Assigned to the field.

  The following GO annotation applies to previously known proteins. The following annotations were found: annotations related to biological processes: ossification, anti-apoptotic, inflammatory response, cell-substrate adhesion, cell-cell signaling, annotation related to molecular function Extracellular substrates that are annotations related to protective / immune proteins, cytokines, integrin ligands, protein binding, growth factors, apoptosis inhibitors, and cellular components.

  GO assignments can be made at one or more http: // www. expasy. SwissProt / TremBl Protein knowledgebase available from ch / sprot / or http: // www. ncbi. nlm. nih. Depends on Locuslink available from gov / projects / LocusLink /.

  The cluster HUMOSTRO can be used as a diagnostic marker by overexpression of transcripts of this cluster in cancer. The expression of such transcripts in normal tissues is also shown by the method previously described. The terms "numbers" in the right column of the table and the numbers on the y-axis of FIG. 46 refer to the weighted expression of ESTs in each category as "ppm" (the ppm of ESTs of a particular cluster in this category by ppm Ratio of expression to expression of all ESTs).

  In general, as shown for the histograms in FIG. 46 and Table 1222, the following results were obtained. This cluster was overexpressed (at least at minimal levels) in the following pathological conditions: epithelial malignancy, a mixture of malignancies from different tissues, lung malignancy, malignancy breast cancer, ovarian cancer, and skin malignancy.

  As mentioned above, cluster HUMOSTRO is characterized by the three transcripts listed in Table 1 above. These transcripts encode proteins which are variants of the protein osteopontin precursor. A description of each mutein of the invention is provided herein.

  The mutant protein HUMOSTRO_PEA_1_PEA_1_P21 of the present invention has the amino acid sequence shown at the end of the application and is encoded by the transcript HUMOSTRO_PEA_1_PEA_1_T14. An alignment to a known protein (osteopontin precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report on the comparison between HUMOSTRO_PEA_1_PEA_1_P21 and OSTP_HUMAN 1. The amino acid sequence corresponding to amino acids 1-58 of OSTP_HUMAN and corresponding to amino acids 1-58 of HUMOSTRO_PEA_1_P21 corresponds to the amino acid sequence corresponding to HUMOSTRO_PEA_1_PEA_1_P21, and the first amino acid sequence which is at least 90% homologous to Said second amino acid sequence comprising a second amino acid sequence which is at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous; HUMO in which the amino acid sequences of 2 are in contiguous and sequential order Isolated chimeric polypeptide encoding TRO_PEA_1_PEA_1_P21.

  2. HUMOSTRO_PEA_1_P21 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence VFLNFS in HUMOSTRO_PEA_1_PEA_1_P21 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is considered to be secretion by manual investigation of known protein localization and / or gene structure.

  The mutant protein HUMOSTRO_PEA_1_PEA_1_P21 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows the SNPs as shown in Table 1224) It indicates whether it is known and the presence of a known SNP in the mutant protein HUMOSTRO_PEA_1_PEA_1_P21 sequence supports the predicted sequence of this mutant protein of the invention).

  The glycosylation sites of the mutant protein HUMOSTRO_PEA_1_PEA_1_P21 compared to the known protein osteopontin precursor are shown in Table 1225 (showing its position on the amino acid sequence in the first column, the second column has a glycosylation site in the mutant protein) The last column indicates whether this position differs on the mutant protein).

  The mutein, HUMOSTRO_PEA_1_PEA_1_P21, is encoded by the following transcript: HUMOSTRO_PEA_1_PEA_1_T14 (sequences shown at the end of the application). The code portion of the transcript HUMOSTRO_PEA_1_PEA_1_T14 is shown in bold, starting from position 199 and ending at position 390. The transcript also has the following SNPs listed in Table 1226 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, the mutant protein HUMOSTRO_PEA_1_PEA_1_P21 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutant protein HUMOSTRO_PEA_1_PEA_1_P25 according to the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript HUMOSTRO_PEA_1_PEA_1_T16. An alignment to a known protein (osteopontin precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report on the comparison between HUMOSTRO_PEA_1_PEA_1_P25 and OSTP_HUMAN 1. A polypeptide having a first amino acid sequence which is at least 90% homologous to MRIAVICFCLLGITCAIPVKQADSGSSEEKQ corresponding to amino acids 1 to 31 of OSTP HUMAN and corresponding to amino acids 1 to 31 of HUMOSTRO PEA 1 _P 25 and a polypeptide having sequence H corresponding to amino acids 32 to 32 of HUMOSTRO PEA 1 _PEA 1 _P25 Said second amino acid sequence comprising a second amino acid sequence which is at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous; An isolated chimeric polypeptide encoding HUMOSTRO_PEA_1_PEA_1_P25, wherein the two amino acid sequences are in contiguous and sequential order Peptide.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutant protein HUMOSTRO_PEA_1_PEA_1_P25 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows SNPs as shown in Table 1227) It indicates whether it is known and the presence of a known SNP in the mutant protein HUMOSTRO_PEA_1_PEA_1_P25 sequence supports the deduced sequence of this mutant protein according to the invention).

  The glycosylation sites of the mutant protein HUMOSTRO_PEA_1_PEA_1_P25 compared to the known protein osteopontin precursor are shown in Table 1228 (showing its position on the amino acid sequence in the first column, the second column has a glycosylation site in the mutant protein) The last column indicates whether this position differs on the mutant protein).

  The mutein, HUMOSTRO_PEA_1_PEA_1_P25, is encoded by the following transcript: HUMOSTRO_PEA_1_PEA_1_T16 (sequences shown at the end of the application). The code portion of the transcript HUMOSTRO_PEA_1_PEA_1_T16 is shown in bold, starting from position 199 and ending at position 294. The transcript also has the following SNPs listed in Table 1229 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, the mutein HUMOSTRO_PEA_1_PEA_1_P25 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutant protein HUMOSTRO_PEA_1_PEA_1_P30 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript HUMOSTRO_PEA_1_PEA_1_T30. An alignment to a known protein (osteopontin precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Reporting of the comparison between HUMOSTRO_PEA_1_PEA_1_P30 and OSTP_HUMAN 1. A polypeptide having a first amino acid sequence corresponding to amino acids 1 to 31 of OSTP HUMAN and corresponding to amino acids 1 to 31 of HUMOSTRO PEA 1 _ PEA 1 _P30 and a sequence VSIFY VFI corresponding to amino acids 32 to 39 of HUMOSTRO PEA 1 _PEA 1 _P30, which is at least 90% homologous to Said second amino acid sequence comprising a second amino acid sequence which is at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous; Amino acid sequences of SEQ ID NO: 2 encode HUMOSTRO_PEA_1_PEA_1_P30, in contiguous and sequential order Isolated chimeric polypeptide.

  2. HUMOSTRO_PEA_1_P30 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence VSIFYVFI in HUMOSTRO_PEA_1_PEA_1_P30 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutant protein HUMOSTRO_PEA_1_PEA_1_P30 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing the other amino acids, and the last column shows the SNPs, as shown in Table 1230) It indicates whether it is known and the presence of a known SNP in the mutant protein HUMOSTRO_PEA_1_PEA_1_P30 sequence supports the putative sequence of this mutant protein of the invention).

  The glycosylation sites of the mutant protein HUMOSTRO_PEA_1_PEA_1_P30 compared to the known protein osteopontin precursor are shown in Table 1231 (showing its position on the amino acid sequence in the first column, the second column has a glycosylation site in the mutant protein) The last column indicates whether this position differs on the mutant protein).

  The mutein, HUMOSTRO_PEA_1_PEA_1_P30, is encoded by the following transcript: HUMOSTRO_PEA_1_PEA_1_T30 (sequences shown at the end of the application). The code portion of the transcript HUMOSTRO_PEA_1_PEA_1_T30 is shown in bold, starting from position 199 and ending at position 315. The transcript also has the following SNPs listed in Table 1232 (indicating its position on the nucleotide sequence and listing another nucleic acid, the last column indicates whether the SNP is known, the mutant protein HUMOSTRO_PEA_1_PEA_1_P30 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  As mentioned above, the cluster HUMOSTRO is characterized by the 30 segments listed in Table 2 above, the sequence of which is shown at the end of the application. These segments are part of the nucleic acid sequence, which are of particular interest and are individually described herein. A description of each segment of the invention is provided herein.

  The segment cluster HUMOSTRO_PEA_1_PEA_1_node_0 of the present invention is supported by 333 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMOSTRO_PEA_1_PEA_1_T14, HUMOSTRO_PEA_1_PEA_1_T16, and HUMOSTRO_PEA_1_PEA_1_T30. Table 1233 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMOSTRO_PEA_1_PEA_1_node_10 of the present invention is supported by 4 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMOSTRO_PEA_1_PEA_1_T16. Table 1235 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMOSTRO_PEA_1_PEA_1_node_16 of the present invention is supported by six libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMOSTRO_PEA_1_PEA_1_T14. Table 1236 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMOSTRO_PEA_1_PEA_1_node_23 of the present invention is supported by 334 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMOSTRO_PEA_1_PEA_1_T14 and HUMOSTRO_PEA_1_PEA_1_T16. Table 1237 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMOSTRO_PEA_1_PEA_1_node_31 of the present invention is supported by 350 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMOSTRO_PEA_1_PEA_1_T14 and HUMOSTRO_PEA_1_PEA_1_T16. Table 1238 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMOSTRO_PEA_1_PEA_1_node_43 of the present invention is supported by 192 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMOSTRO_PEA_1_PEA_1_T14 and HUMOSTRO_PEA_1_PEA_1_T16. Table 1239 below describes the start and end positions of this segment on each transcript.

  According to an optional embodiment of the present invention, there is also provided a short segment associated with the above cluster. These segments are up to about 120 bp in length and are therefore included in the individual descriptions.

  The segment cluster HUMOSTRO_PEA_1_PEA_1_node_3 of the present invention is supported by 353 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMOSTRO_PEA_1_PEA_1_T14, HUMOSTRO_PEA_1_PEA_1_T16, and HUMOSTRO_PEA_1_PEA_1_T30. Table 1240 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMOSTRO_PEA_1_PEA_1_node_5 of the present invention is supported by 353 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMOSTRO_PEA_1_PEA_1_T14, HUMOSTRO_PEA_1_PEA_1_T16, and HUMOSTRO_PEA_1_PEA_1_T30. Table 1241 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMOSTRO_PEA_1_PEA_1_node_7 of the present invention is supported by 357 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: HUMOSTRO_PEA_1_PEA_1_T14, HUMOSTRO_PEA_1_PEA_1_T16, and HUMOSTRO_PEA_1_PEA_1_T30. Table 1242 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMOSTRO_PEA_1_PEA_1_node_8 of the present invention is supported by one library. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMOSTRO_PEA_1_PEA_1_T30. Table 1243 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMOSTRO_PEA_1_PEA_1_node_15 of the present invention is supported by 366 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMOSTRO_PEA_1_PEA_1_T14 and HUMOSTRO_PEA_1_PEA_1_T16. Table 1244 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMOSTRO_PEA_1_PEA_1_node_17 of the present invention is supported by 261 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMOSTRO_PEA_1_PEA_1_T14 and HUMOSTRO_PEA_1_PEA_1_T16. Table 1245 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMOSTRO_PEA_1_PEA_1_node_20 according to the invention can be found in the following transcripts: HUMOSTRO_PEA_1_PEA_1_T14 and HUMOSTRO_PEA_1_PEA_1_T16. Table 1246 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMOSTRO_PEA_1_PEA_1_node_21 of the present invention is supported by 315 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMOSTRO_PEA_1_PEA_1_T14 and HUMOSTRO_PEA_1_PEA_1_T16. Table 1247 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMOSTRO_PEA_1_PEA_1_node_22 of the present invention is supported by 322 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMOSTRO_PEA_1_PEA_1_T14 and HUMOSTRO_PEA_1_PEA_1_T16. Table 1248 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMOSTRO_PEA_1_PEA_1_node_24 of the present invention is supported by 270 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMOSTRO_PEA_1_PEA_1_T14 and HUMOSTRO_PEA_1_PEA_1_T16. Table 1249 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMOSTRO_PEA_1_PEA_1_node_26 according to the invention can be found in the following transcripts: HUMOSTRO_PEA_1_PEA_1_T14 and HUMOSTRO_PEA_1_PEA_1_T16. Table 1250 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMOSTRO_PEA_1_PEA_1_node_27 of the present invention is supported by 260 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMOSTRO_PEA_1_PEA_1_T14 and HUMOSTRO_PEA_1_PEA_1_T16. Table 1251 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMOSTRO_PEA_1_PEA_1_node_28 of the present invention is supported by 273 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMOSTRO_PEA_1_PEA_1_T14 and HUMOSTRO_PEA_1_PEA_1_T16. Table 1252 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMOSTRO_PEA_1_PEA_1_node_29 of the present invention is supported by 272 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMOSTRO_PEA_1_PEA_1_T14 and HUMOSTRO_PEA_1_PEA_1_T16. Table 1253 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMOSTRO_PEA_1_PEA_1_node_30 according to the invention can be found in the following transcripts: HUMOSTRO_PEA_1_PEA_1_T14 and HUMOSTRO_PEA_1_PEA_1_T16. Table 1254 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMOSTRO_PEA_1_PEA_1_node_32 of the present invention is supported by 293 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMOSTRO_PEA_1_PEA_1_T14 and HUMOSTRO_PEA_1_PEA_1_T16. Table 1255 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMOSTRO_PEA_1_PEA_1_node_34 of the present invention is supported by 301 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMOSTRO_PEA_1_PEA_1_T14 and HUMOSTRO_PEA_1_PEA_1_T16. Table 1256 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMOSTRO_PEA_1_PEA_1_node_36 of the present invention is supported by 292 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMOSTRO_PEA_1_PEA_1_T14 and HUMOSTRO_PEA_1_PEA_1_T16. Table 1257 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMOSTRO_PEA_1_PEA_1_node_37 of the present invention is supported by 295 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMOSTRO_PEA_1_PEA_1_T14 and HUMOSTRO_PEA_1_PEA_1_T16. Table 1258 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMOSTRO_PEA_1_PEA_1_node_38 according to the invention can be found in the following transcripts: HUMOSTRO_PEA_1_PEA_1_T14 and HUMOSTRO_PEA_1_PEA_1_T16. Table 1259 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMOSTRO_PEA_1_PEA_1_node_39 of the present invention is supported by 268 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMOSTRO_PEA_1_PEA_1_T14 and HUMOSTRO_PEA_1_PEA_1_T16. Table 1260 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMOSTRO_PEA_1_PEA_1_node_40 according to the invention can be found in the following transcripts: HUMOSTRO_PEA_1_PEA_1_T14 and HUMOSTRO_PEA_1_PEA_1_T16. Table 1261 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMOSTRO_PEA_1_PEA_1_node_41 according to the invention can be found in the following transcripts: HUMOSTRO_PEA_1_PEA_1_T14 and HUMOSTRO_PEA_1_PEA_1_T16. Table 1262 below describes the start and end positions of this segment on each transcript.

  The segment cluster HUMOSTRO_PEA_1_PEA_1_node_42 of the present invention is supported by 224 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: HUMOSTRO_PEA_1_PEA_1_T14 and HUMOSTRO_PEA_1_PEA_1_T16. Table 1263 below describes the start and end positions of this segment on each transcript.

Mutated protein alignment against previously known proteins:
Sequence name: OSTP_HUMAN

Sequence documentation:

Alignment of: HUMOSTRO_PEA_1_PEA_1_P21 x OSTP_HUMAN ..

Alignment segment 1/1:

Quality: 578.00 Escore: 0
Matching length: 58 Total length: 58
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MRIAVICFCLLGITCAIPVKQADGSSEEKQLYNKYPDATWLNPDPSQ 50
||||||||||||||||||||||||||||||||||||||||
1 MRIAVICFCLLGITCAIPVKQADGSSEEKQLYNKYPDATWLNPDPSQ 50

51 KQNLLAPQ 58
||||||||
51 KQNLLAPQ 58






Sequence name: OSTP_HUMAN

Sequence documentation:

Alignment of: HUMOSTRO_PEA_1_PEA_1_P25 x OSTP_HUMAN ..

Alignment segment 1/1:

Quality: 301.00 Escore: 0
Matching length: 31 Total length: 31
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MRIAVICFCLLGITCAIPVKQADGSSEEKQ 31
|||||||||||||||||||||||||||||
1 MRIAVICFCLLGITCAIPVKQADGSSEEKQ 31






Sequence name: OSTP_HUMAN

Sequence documentation:

Alignment of: HUMOSTRO_PEA_1_PEA_1_P30 x OSTP_HUMAN ..

Alignment segment 1/1:

Quality: 301.00 Escore: 0
Matching length: 31 Total length: 31
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MRIAVICFCLLGITCAIPVKQADGSSEEKQ 31
|||||||||||||||||||||||||||||
1 MRIAVICFCLLGITCAIPVKQADGSSEEKQ 31

Description of cluster R11723 Cluster R11723 is characterized by 6 transcripts and 26 segments of interest, the names of which are given in Tables 1264 and 1265 respectively, and the sequence itself is given at the end of the application. Selected protein variants are shown in Table 1266.

  Cluster R11723 can be used as a diagnostic marker by overexpression of transcripts of this cluster in cancer. The expression of such transcripts in normal tissues is also shown by the method previously described. The terms "numbers" in the right column of the table and the numbers on the y-axis of Fig. 47 refer to the weighted expression of ESTs in each category as "ppm" (the ppm of ESTs of a particular cluster in this category by ppm Ratio of expression to expression of all ESTs).

  In general, as shown for the histograms in FIG. 47 and Table 1267, the following results were obtained. This cluster was overexpressed (at least at minimal levels) in the following pathological conditions: epithelial malignancies, a mixture of malignancies from different tissues, and kidney malignancies.

  As mentioned above, contig R11723 is characterized by the six transcripts listed in Table 1 above. A description of each mutein of the invention is provided herein.

  The mutein R11723_PEA_1_P2 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript R11723_PEA_1_T6. The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein R11723_PEA_1_P2 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, enumerating other amino acids, and the last column shows SNPs as shown in Table 1269) It indicates whether it is known and the presence of a known SNP in the mutein R11723_PEA_1_P2 sequence supports the deduced sequence of this mutein of the invention).

  The mutein, R11723_PEA_1_P2, is encoded by the following transcript: R11723_PEA_1_T6 (sequences shown at the end of the application). The code portion of transcript R11723_PEA_1_T6 is shown in bold and this code portion starts at position 1716 and ends at position 2051. The transcript also has the following SNPs listed in Table 1270 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein R11723_PEA_1_P2 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein R11723_PEA_1_P6 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript R11723_PEA_1_T15. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report on the comparison between R11723_PEA_1_P6 and Q8IXM0 (SEQ ID NO: 1707) A polypeptide having at least 70%, optionally at least 80%, at least 90%, and a sequence having the sequence MWVLGIAATFCLCLLPGFALQIGQCYQCEEFLFNNDSSPEFIVNCTCNVQDQQQEVMESAGMYRKASCSACLIASEGSPCRGLAPGREEQRALHKAGAGGGGVR corresponding to amino acids 1 to 110 of R11723_PEA_1_P6 The amino acid sequence of SEQ ID NO: 1 and MYAQALLVVGVLQRQAAAQHLHEHPPKLLRGHRVQERVDDRAE corresponding to amino acids 1 to 112 of Q8IXM0 and also to amino acids 111 to 122 of R11723_PEA_1_P6 EKRLREGEEDHVRPEVGPRPVVLGFGRSHDPPNLVGHPAYGQCHNNQPWADTSRRERQRKEKHSMRTQ and and at least 90% homologous to a second amino acid sequence, wherein the first and second amino acid distribution is contiguous, and in sequential order, the isolated chimeric polypeptide coding R11723_PEA_1_P6.

  2. Sequence of R11723_PEA_1_P6 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFELNDCSSPEFIVNCCTNVQDQQQEVMESAGIMYRKSCASSA CLIASA GSPCR GLAPGREEQRALHKAGAVGGGVR and at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 75% An isolated polypeptide encoding

Report on comparison between R11723_PEA_1_P6 and Q96AC2 (SEQ ID NO: 1708) Corresponding to amino acids 1-83 of Q96AC2, ports having a MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMEQSAGIMYRKSCASSAACLIASAG corresponding to amino acids 1-83 of R11723_PEA_1_P6 the first amino acid sequence at least 90% homologous, sequences corresponding to SPCRGLAPGREEQRALHKAGAVGGGVRMYAQALLVVGVLQRQAAAQHLHEHPPKLLRGHRVQERVDDRAEVEKRLREGEEDHVRPEVGPRPVVLGFGRSHDPPNLVGHPAYGQCHNNQPWADTSRRERQRKEKHSMRTQ to amino acid 84-222 of R11723_PEA_1_P6 Said first and second comprising a peptide and a second amino acid sequence which is at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous. An isolated chimeric polypeptide encoding R11723_PEA_1_P6, wherein the amino acid sequences of are in contiguous and sequential order.

  2. In the R117723_PEA_1_P6_R117723_PEA_I_P6 A sub-block s / s / s / s / s. An isolated polypeptide encoding a tail.

Report of comparison between R11723_PEA_1_P6 and Q8N2G4 (SEQ ID NO: 1709) Corresponding to amino acids 1-83 of Q8N2G4, ports having a MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMEQSAGIMYRKSCASSAACLIASAG corresponding to amino acids 1-83 of R11723_PEA_1_P6 the first amino acid sequence at least 90% homologous, sequences corresponding to SPCRGLAPGREEQRALHKAGAVGGGVRMYAQALLVVGVLQRQAAAQHLHEHPPKLLRGHRVQERVDDRAEVEKRLREGEEDHVRPEVGPRPVVLGFGRSHDPPNLVGHPAYGQCHNNQPWADTSRRERQRKEKHSMRTQ to amino acid 84-222 of R11723_PEA_1_P6 Said first and second comprising a peptide and a second amino acid sequence which is at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous. An isolated chimeric polypeptide encoding R11723_PEA_1_P6, wherein the amino acid sequences of are in contiguous and sequential order.

  2. In the R117723_PEA_1_P6_R117723_PEA_I_P6 A sub-block s / s / s / s / s. An isolated polypeptide encoding a tail.

Report on comparison between R11723_PEA_1_P6 and BAC 85518 (SEQ ID NO: 1710) Corresponding to amino acids 24-106 of BAC85518, first amino acid sequence at least 90% homologous to the corresponding MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMEQSAGIMYRKSCASSAACLIASAG to amino acids 1-83 of R11723_PEA_1_P6, the corresponding sequence SPCRGLAPGREEQRALHKAGAVGGGVRMYAQALLVVGVLQRQAAAQHLHEHPPKLLRGHRVQERVDDRAEVEKRLREGEEDHVRPEVGPRPVVLGFGRSHDPPNLVGHPAYGQCHNNQPWADTSRRERQRKEKHSMRTQ to amino acid 84-222 of R11723_PEA_1_P6 A second amino acid sequence which is at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous to the An isolated chimeric polypeptide encoding R11723_PEA_1_P6, wherein the second amino acid sequence is in contiguous and sequential order.

  2. In the R117723_PEA_1_P6_R117723_PEA_I_P6 A sub-block s / s / s / s / s. An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein R11723_PEA_1_P6 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, enumerating other amino acids, and the last column shows SNPs as shown in Table 1271) It is indicated whether it is known and the presence of a known SNP in the mutein R11723_PEA_1_P6 sequence supports the putative sequence of this mutein of the invention).

  The mutein R11723_PEA_1_P6 is encoded by the following transcript: R11723_PEA_1_T15 (sequences shown at the end of the application). The coding part of the transcript R11723_PEA_1_T15 is shown in bold, starting from position 434 and ending at position 1099. The transcript also has the following SNPs listed in Table 1272 (showing its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein R11723_PEA_1_P6 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein R11723_PEA_1_P7 according to the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript R11723_PEA_1_T17. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between R11723_PEA_1_P7 and Q96AC2 Corresponding to amino acids 1 to 64 of Q96AC2 and corresponding to amino acids 1 to 64 of R11723_PEA_1_P7. A first amino acid sequence that is at least 90% homologous to QIQCQQQVMMEQSAG and a corresponding amino acid sequence Said first and second amino acids comprising a second amino acid sequence which is at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous The arrangement is adjacent and in sequential order, R1172 Isolated chimeric polypeptide encoding _PEA_1_P7.

  2. R11723_PEA_1_P7 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT in R11723_PEA_1_P7 An isolated polypeptide encoding a tail.

Report of comparison between R11723_PEA_1_P7 and Q8N2G4 A first amino acid sequence corresponding to amino acids 1 to 64 of Q8N2G4 and corresponding to amino acids 1 to 64 of R11723_PEA_1_P7 is a first amino acid sequence at least 90% homologous to the amino acid sequence Said first and second amino acids comprising a second amino acid sequence which is at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous The arrangement is adjacent and in sequential order, R1172 Isolated chimeric polypeptide encoding _PEA_1_P7.

  2. R11723_PEA_1_P7 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT in R11723_PEA_1_P7 An isolated polypeptide encoding a tail.

Report of comparison between R11723_PEA_1_P7 and BAC 85 271. A polypeptide having a sequence MWVLG corresponding to amino acids 1 to 5 of R11723_PEA_1_P7 at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous 1 and the second amino acid sequence corresponding to amino acids 22 to 80 of BAC 85 273 and corresponding to amino acids 6 to 64 of R11723_PEA_1_P7 corresponding to IAATFCGLFLLPGFALQIQCYQCEEFELNDCSSPEFIVNCTVNVQDMCMQKEVMEQSAG corresponding to amino acids 65 to 93 of R11723_PEA_1_P7 Polypep with SHCVTRLECSGTISAHCNLCLPGSNDHPT And a third amino acid sequence which is at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous; And an isolated chimeric polypeptide encoding R11723_PEA_1_P7, wherein the third amino acid sequence is in contiguous and sequential order.

  2. The tip of R11723_PEA_1_P7 comprising a polypeptide at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence MWVLG of R11723_PEA_1_P7 An isolated polypeptide encoding

  3. R11723_PEA_1_P7 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT in R11723_PEA_1_P7 An isolated polypeptide encoding a tail.

Report on comparison between R11723_PEA_1_P7 and BAC 85518. Corresponding to amino acids 24 to 87 of BAC 85518 and corresponding to amino acids 1 to 64 of R11723_PEA_1_P7. Said first and second amino acids comprising a second amino acid sequence which is at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous The arrangement is adjacent and in sequential order, R 1 Isolated chimeric polypeptide encoding 723_PEA_1_P7.

  2. R11723_PEA_1_P7 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT in R11723_PEA_1_P7 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein R11723_PEA_1_P7 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, enumerating other amino acids, and the last column shows SNPs as shown in Table 1273) It indicates whether it is known and the presence of a known SNP in the mutein R11723_PEA_1_P7 sequence supports the deduced sequence of this mutein according to the invention).

  The mutein, R11723_PEA_1_P7, is encoded by the following transcript: R11723_PEA_1_T17 (sequences shown at the end of the application). The code portion of the transcript R11723_PEA_1_T17 is shown in bold, starting at position 434 and ending at position 712. The transcript also has the following SNPs listed in Table 1274 (showing its position on the nucleotide sequence and listing another nucleic acid, the last column shows whether the SNP is known, mutein R11723_PEA_1_P7 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein R11723_PEA_1_P13 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript R11723_PEA_1_T19. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between R11723_PEA_1_P13 and Q96AC2 A first amino acid sequence corresponding to amino acids 1 to 63 of Q96AC2 and to amino acids 1 to 63 of R11723_PEA_1_P13 and corresponding to MWVLGIAATFCCLFLLPGFALQ IQCYQCEEFELNDCSSPEFIVNCTVNVQDMCQKEVMEQSA a sequence corresponding to amino acids 64 to 84 of R11723_PEA_1_P13 Said first and second amino acids comprising a second amino acid sequence which is at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous R11723_PEA_1, where the arrangements are adjacent and in sequential order Isolated chimeric polypeptide encoding P13.

  2. R11723_PEA_1_P13 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence DTKRTNTLLFEMRHFAKQLTT in R11723_PEA_1_P13 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein R11723_PEA_1_P13 is encoded by the following transcript: R11723_PEA_1_T19 and R11723_PEA_1_T5 (sequences shown at the end of the application). The coding portion of the transcript R11723_PEA_1_T19 is shown in bold, starting at position 434 and ending at position 685. The transcript also has the following SNPs listed in Table 1275 (showing its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein R11723_PEA_1_P13 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein R11723_PEA_1_P10 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript R11723_PEA_1_T20. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between R11723_PEA_1_P10 and Q96AC2 A first amino acid sequence corresponding to amino acids 1 to 63 of Q96AC2 and to amino acids 1 to 63 of R11723_PEA_1_P10 and corresponding to MWVLGIAATFCCFLFLLPGFALQQCYQCEEFQLNNDSSPEFIVNCTVNVQDMCQKEVMEQSA and a sequence corresponding to amino acids 64-90 of the R11723_PEA_1_P10 Said first and second amino acids comprising a second amino acid sequence which is at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous The arrangement is adjacent and in sequential order, R11723 Isolated chimeric polypeptide encoding PEA_1_P10.

  2. R11723_PEA_1_P10 comprising a polypeptide at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence DRVSLCHEAGVQWNNFSTLQPLPPRLK in R11723_PEA_1_P10 An isolated polypeptide encoding a tail.

Report of comparison between R11723_PEA_1_P10 and Q8N2G4 A first amino acid sequence corresponding to amino acids 1 to 63 of Q8N2G4 and corresponding to amino acids 1 to 63 of R11723_PEA_1_P10, and a corresponding amino acid sequence Said first and second amino acids comprising a second amino acid sequence which is at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous The arrangement is adjacent and in sequential order, R11723 Isolated chimeric polypeptide encoding PEA_1_P10.

  2. R11723_PEA_1_P10 comprising a polypeptide at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence DRVSLCHEAGVQWNNFSTLQPLPPRLK in R11723_PEA_1_P10 An isolated polypeptide encoding a tail.

Report of comparison between R11723_PEA_1_P10 and BAC 85 271. A polypeptide having a sequence MWVLG corresponding to amino acids 1 to 5 of R11723_PEA_1_P10 at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous The amino acid sequence of 1 and the second amino acid sequence corresponding to amino acids 22 to 79 of BAC 85 273 and corresponding to amino acids 6 to 63 of R11723_PEA_1_P10 and corresponding to amino acids 6 to 63 Polypep with DRVSLCHEAGVQWNNFSTLQPLPPRLK And a third amino acid sequence which is at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous; And an isolated chimeric polypeptide encoding R11723_PEA_1_P10, wherein the third amino acid sequence is adjacent and in sequential order.

  2. The tip of R11723_PEA_1_P10, comprising a polypeptide at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence MWVLG of R11723_PEA_1_P10 An isolated polypeptide encoding

  3. R11723_PEA_1_P10 comprising a polypeptide at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence DRVSLCHEAGVQWNNFSTLQPLPPRLK in R11723_PEA_1_P10 An isolated polypeptide encoding a tail.

Report of comparison between R11723_PEA_1_P10 and BAC 85518. A first amino acid sequence corresponding to amino acids 24 to 86 of BAC 85518 and corresponding to amino acids 1 to 63 of R11723_PEA_1_P10, MWVLGIAATFCCLFLLPGFALQIQCYQCEEFQLNNDSSPEFIVNCCTV NVQDMCQKEVMEQSA, and a corresponding amino acid 74 UTs Said first and second amino acids comprising a second amino acid sequence which is at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous The arrangements are adjacent and in sequential order, R 11 Isolated chimeric polypeptide encoding 23_PEA_1_P10.

  2. R11723_PEA_1_P10 comprising a polypeptide at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence DRVSLCHEAGVQWNNFSTLQPLPPRLK in R11723_PEA_1_P10 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein R11723_PEA_1_P10 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows SNPs as shown in Table 1276) It indicates whether it is known and the presence of a known SNP in the mutein R11723_PEA_1_P10 sequence supports the deduced sequence of this mutein according to the invention).

  The mutein, R11723_PEA_1_P10, is encoded by the following transcript: R11723_PEA_1_T20 (sequences shown at the end of the application). The coding part of the transcript R11723_PEA_1_T20 is shown in bold, starting from position 434 and ending at position 703. The transcript also has the following SNPs listed in Table 1277 (showing its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein R11723_PEA_1_P10 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  As mentioned above, cluster R11723 is characterized by the 26 segments listed in Table 2 above, the sequence of which is shown at the end of the application. These segments are part of the nucleic acid sequence, which are of particular interest and are individually described herein. A description of each segment of the invention is provided herein.

  The segment cluster R11723_PEA_1_node_13 of the present invention is supported by five libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R11723_PEA_1_T19, R11723_PEA_1_T5, and R11723_PEA_1_T6. Table 1278 below describes the start and end positions of this segment on each transcript.

  The segment cluster R11723_PEA_1_node_16 of the present invention is supported by three libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R11723_PEA_1_T17, R11723_PEA_1_T19, and R11723_PEA_1_T20. Table 1279 below describes the start and end positions of this segment on each transcript.

  The segment cluster R11723_PEA_1_node_19 of the present invention is supported by 45 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R11723_PEA_1_T5 and R11723_PEA_1_T6. Table 1280 below describes the start and end positions of this segment on each transcript.

  The segment cluster R11723_PEA_1_node_2 of the present invention is supported by 29 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: R11723_PEA_1_T15, R11723_PEA_1_T17, R11723_PEA_1_T19, R11723_PEA_1_T20, R11723_PEA_1_T5, and R11723_PEA_1_T6. Table 1281 below describes the start and end positions of this segment on each transcript.

  The segment cluster R11723_PEA_1_node_22 of the present invention is supported by 65 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R11723_PEA_1_T5 and R11723_PEA_1_T6. Table 1282 below describes the start and end positions of this segment on each transcript.

  The segment cluster R11723_PEA_1_node_31 of the present invention is supported by 70 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R11723_PEA_1_T15, R11723_PEA_1_T5, and R11723_PEA_1_T6. Table 1283 below describes the start and end positions of this segment on each transcript (note that these transcripts show additional polyadenylation).

  According to an optional embodiment of the present invention, there is also provided a short segment associated with the above cluster. These segments are up to about 120 bp in length and are therefore included in the individual descriptions.

  The segment cluster R11723_PEA_1_node_10 of the present invention is supported by 38 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: R11723_PEA_1_T15, R11723_PEA_1_T17, R11723_PEA_1_T19, R11723_PEA_1_T20, R11723_PEA_1_T5, and R11723_PEA_1_T6. Table 1284 below describes the start and end positions of this segment on each transcript.

  The segment cluster R11723_PEA_1_node_11 of the present invention is supported by 42 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: R11723_PEA_1_T15, R11723_PEA_1_T17, R11723_PEA_1_T19, R11723_PEA_1_T20, R11723_PEA_1_T5, and R11723_PEA_1_T6. Table 1285 below describes the start and end positions of this segment on each transcript.

  The segment cluster R11723_PEA_1_node_15 of the invention can be found in the following transcript: R11723_PEA_1_T20. Table 1286 below describes the start and end positions of this segment on each transcript.

  The segment cluster R11723_PEA_1_node_18 of the present invention is supported by 40 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R11723_PEA_1_T15, R11723_PEA_1_T5, and R11723_PEA_1_T6. Table 1287 below describes the start and end positions of this segment on each transcript.

  The segment cluster R11723_PEA_1_node_20 according to the invention can be found in the following transcript: R11723_PEA_1_T5 and R11723_PEA_1_T6. Table 1288 below describes the start and end positions of this segment on each transcript.

  The segment cluster R11723_PEA_1_node_21 of the present invention is supported by 36 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R11723_PEA_1_T5 and R11723_PEA_1_T6. Table 1289 below describes the start and end positions of this segment on each transcript.

  The segment cluster R11723_PEA_1_node_23 of the present invention is supported by 39 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R11723_PEA_1_T5 and R11723_PEA_1_T6. Table 1290 below describes the start and end positions of this segment on each transcript.

  The segment cluster R11723_PEA_1_node_24 of the present invention is supported by 51 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R11723_PEA_1_T15, R11723_PEA_1_T5, and R11723_PEA_1_T6. Table 1291 below describes the start and end position of this segment on each transcript.

  The segment cluster R11723_PEA_1_node_25 of the present invention is supported by 54 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R11723_PEA_1_T15, R11723_PEA_1_T5, and R11723_PEA_1_T6. Table 1292 below describes the start and end positions of this segment on each transcript.

  The segment cluster R11723_PEA_1_node_26 of the present invention is supported by 62 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R11723_PEA_1_T15, R11723_PEA_1_T5, and R11723_PEA_1_T6. Table 1293 below describes the start and end positions of this segment on each transcript.

  The segment cluster R11723_PEA_1_node_27 of the present invention is supported by 67 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R11723_PEA_1_T15, R11723_PEA_1_T5, and R11723_PEA_1_T6. Table 1294 below describes the start and end positions of this segment on each transcript.

  The segment cluster R11723_PEA_1_node_28 of the invention can be found in the following transcripts: R11723_PEA_1_T15, R11723_PEA_1_T5, and R11723_PEA_1_T6. Table 1295 below describes the start and end positions of this segment on each transcript.

  The segment cluster R11723_PEA_1_node_29 of the present invention is supported by 69 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R11723_PEA_1_T15, R11723_PEA_1_T5, and R11723_PEA_1_T6. Table 1296 below describes the start and end positions of this segment on each transcript.

  The segment cluster R11723_PEA_1_node_3 according to the invention can be found in the following transcripts: R11723_PEA_1_T15, R11723_PEA_1_T17, R11723_PEA_1_T19, R11723_PEA_1_T20, R11723_PEA_1_T5, and R11723_PEA_1_T6. Table 1297 below describes the start and end positions of this segment on each transcript.

  The segment cluster R11723_PEA_1_node_30 according to the invention can be found in the following transcripts: R11723_PEA_1_T15, R11723_PEA_1_T5, and R11723_PEA_1_T6. Table 1298 below describes the start and end positions of this segment on each transcript.

  The segment cluster R11723_PEA_1_node_4 of the present invention is supported by 25 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: R11723_PEA_1_T15, R11723_PEA_1_T17, R11723_PEA_1_T19, R11723_PEA_1_T20, R11723_PEA_1_T5, and R11723_PEA_1_T6. Table 1299 below describes the start and end positions of this segment on each transcript.

  The segment cluster R11723_PEA_1_node_5 of the present invention is supported by 26 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: R11723_PEA_1_T15, R11723_PEA_1_T17, R11723_PEA_1_T19, R11723_PEA_1_T20, R11723_PEA_1_T5, and R11723_PEA_1_T6. Table 1300 below lists the start and end positions of this segment on each transcript.

  The segment cluster R11723_PEA_1_node_6 of the present invention is supported by 27 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: R11723_PEA_1_T15, R11723_PEA_1_T17, R11723_PEA_1_T19, R11723_PEA_1_T20, R11723_PEA_1_T5, and R11723_PEA_1_T6. Table 1301 below describes the start and end positions of this segment on each transcript.

  The segment cluster R11723_PEA_1_node_7 of the present invention is supported by 29 libraries. The number of libraries was determined as described above. This segment can be found in the following transcripts: R11723_PEA_1_T15, R11723_PEA_1_T17, R11723_PEA_1_T19, R11723_PEA_1_T20, R11723_PEA_1_T5, and R11723_PEA_1_T6. Table 1302 below describes the start and end positions of this segment on each transcript.

  The segment cluster R11723_PEA_1_node_8 of the present invention is supported by two libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R11723_PEA_1_T6. Table 1303 below describes the start and end positions of this segment on each transcript.

Mutated protein alignment against previously known proteins:
Sequence name: / tmp / gp6eQTLWqk / mFtjUpUzhb: Q8IXM0

Sequence documentation:

Alignment of: R11723_PEA_1_P6 x Q8IXM0 ..

Alignment segment 1/1:

Quality: 1128.00 Escore: 0
Matching length: 112 Total length: 112
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
111 MYAQALLVVGVLQRQAAAQHLHEHPPKLLRGHRVQERVDDRAEVEKRLRE 160
||||||||||||||||||||||||||||||||||||||||
1 MYAQALLVVGVLQRQAAAQHLHEHPPKLLRGHRVQERVDDRAEVEKRLRE 50
....
161 GEEDHVRPEVGPRPVVLGFGRSHDPPTNLVGHPAYGQCHNNQPWADTSRRE 210
||||||||||||||||||||||||||||||||||||||||
51 GEEDHVRPEVGPRPPVVLGFGRSHDPPTNLVGHPAYGQCHNNQPWADTSRRE 100
.
211 RQRKEKHSMRTQ 222
||||||||||||
101 RQRKEKHSMRTQ 112






Sequence name: / tmp / gp6eQTLWqk / mFtjUpUzhb: Q96AC2

Sequence documentation:

Alignment of: R11723_PEA_1_P6 x Q96AC2 ..

Alignment segment 1/1:

Quality: 835.00 Escore: 0
Matching length: 83 Total length: 83
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50
||||||||||||||||||||||||||||||||||||||||
1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50
....
51 QDMCQKEVMEQSAGIMYRKSCASSAACLIASAG 83
||||||||||||||||||||||||||||||
51 QDMCQKEVMEQSAGIMYRKSCASSAACLIASAG 83






Sequence name: / tmp / gp6eQTLWqk / mFtjUpUzhb: Q8N2G4

Sequence documentation:

Alignment of: R11723_PEA_1_P6 x Q8N2G4 ..

Alignment segment 1/1:

Quality: 835.00 Escore: 0
Matching length: 83 Total length: 83
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50
||||||||||||||||||||||||||||||||||||||||
1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50
....
51 QDMCQKEVMEQSAGIMYRKSCASSAACLIASAG 83
||||||||||||||||||||||||||||||
51 QDMCQKEVMEQSAGIMYRKSCASSAACLIASAG 83






Sequence name: / tmp / gp6eQTLWqk / mFtjUpUzhb: BAC85518

Sequence documentation:

Alignment of: R11723_PEA_1_P6 x BAC85518 ..

Alignment segment 1/1:

Quality: 835.00 Escore: 0
Matching length: 83 Total length: 83
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50
||||||||||||||||||||||||||||||||||||||||
24 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 73
....
51 QDMCQKEVMEQSAGIMYRKSCASSAACLIASAG 83
||||||||||||||||||||||||||||||
74 QDMCQKEVMEQSAGIMYRKSCASSAACLIASAG 106






Sequence name: / tmp / VXjdFlzdBX / bexTxTh0Th: Q96AC2

Sequence documentation:

Alignment of: R11723_PEA_1_P7 x Q96AC2 ..

Alignment segment 1/1:

Quality: 654.00 Escore: 0
Matching length: 64 Total length: 64
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50
||||||||||||||||||||||||||||||||||||||||
1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50
.
51 QDMCQKEVMEQSAG 64
|||||||||||||
51 QDMCQKEVMEQSAG 64






Sequence name: / tmp / VXjdFlzdBX / bexTxTh0Th: Q8N2G4

Sequence documentation:

Alignment of: R11723_PEA_1_P7 x Q8N2G4 ..

Alignment segment 1/1:

Quality: 654.00 Escore: 0
Matching length: 64 Total length: 64
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50
||||||||||||||||||||||||||||||||||||||||
1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50
.
51 QDMCQKEVMEQSAG 64
|||||||||||||
51 QDMCQKEVMEQSAG 64






Sequence name: / tmp / VXjdFlzdBX / bexTxTh0Th: BAC85273

Sequence documentation:

Alignment of: R11723_PEA_1_P7 x BAC85273 ..

Alignment segment 1/1:

Quality: 600.00 Escore: 0
Matching length: 59 Total length: 59
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
6 IAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQ 55
||||||||||||||||||||||||||||||||||||||||
22 IAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQ 71

56 KEVMEQSAG 64
|||||||||
72 KEVMEQSAG 80






Sequence name: / tmp / VXjdFlzdBX / bexTxTh0Th: BAC 85518

Sequence documentation:

Alignment of: R11723_PEA_1_P7 x BAC85518 ..

Alignment segment 1/1:

Quality: 654.00 Escore: 0
Matching length: 64 Total length: 64
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50
||||||||||||||||||||||||||||||||||||||||
24 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 73
.
51 QDMCQKEVMEQSAG 64
|||||||||||||
74 QDMCQKEVMEQSAG 87






Sequence name: / tmp / OLMSexEmIh / pc7Z7Xm1YR: Q96AC2

Sequence documentation:

Alignment of: R11723_PEA_1_P10 x Q96AC2 ..

Alignment segment 1/1:

Quality: 645.00 Escore: 0
Matching length: 63 Total length: 63
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50
||||||||||||||||||||||||||||||||||||||||
1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50
.
51 QDMCQKEVMEQSA 63
||||||||||||
51 QDMCQKEVMEQSA 63






Sequence name: / tmp / OLMSexEmIh / pc7Z7Xm1YR: Q8N2G4

Sequence documentation:

Alignment of: R11723_PEA_1_P10 x Q8N2G4 ..

Alignment segment 1/1:

Quality: 645.00 Escore: 0
Matching length: 63 Total length: 63
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50
||||||||||||||||||||||||||||||||||||||||
1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50
.
51 QDMCQKEVMEQSA 63
||||||||||||
51 QDMCQKEVMEQSA 63






Sequence name: / tmp / OLMSexEmIh / pc7Z7Xm1YR: BAC85273

Sequence documentation:

Alignment of: R11723_PEA_1_P10 x BAC85273 ..

Alignment segment 1/1:

Quality: 591.00 Escore: 0
Matching length: 58 Total length: 58
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
6 IAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQ 55
||||||||||||||||||||||||||||||||||||||||
22 IAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQ 71

56 KEVMEQSA 63
||||||||
72 KEVMEQSA 79






Sequence name: / tmp / OLMSexEmIh / pc7Z7Xm1YR: BAC85518

Sequence documentation:

Alignment of: R11723_PEA_1_P10 x BAC85518 ..

Alignment segment 1/1:

Quality: 645.00 Escore: 0
Matching length: 63 Total length: 63
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50
||||||||||||||||||||||||||||||||||||||||
24 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 73
.
51 QDMCQKEVMEQSA 63
||||||||||||
74 QDMCQKEVMEQSA 86






Alignment of: R11723_PEA_1_P13 x Q96AC2 ..

Alignment segment 1/1:

Quality: 645.00 Escore: 0
Matching length: 63 Total length: 63
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50
||||||||||||||||||||||||||||||||||||||||
1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50
.
51 QDMCQKEVMEQSA 63
||||||||||||
51 QDMCQKEVMEQSA 63

  The nucleotide transcript sequence of a known protein (PSEC, also referred to herein as "wild-type" or WT protein) is characterized by at least one SNP, which affects the coding region in addition to certain silent SNPs. It should be noted that it seems to give. This SNP does not affect the R11723_PEA_1_T5 splice variant sequence ("G->"), but loses nucleotides (impacts amino acids 91 and beyond). The lost nucleotides cause a frameshift and produce a new protein. This SNP has not been previously identified and is supported by 5 of the approximately 70 ESTs in this exon.

  It should be noted that variants of this cluster are variants of the hypothetical protein PSEC0181 (referred to herein as "PSEC"). Furthermore, the use of known proteins (WT proteins) alone or in combination with one or more variants of this cluster and / or any other clusters and / or any known markers for the detection of lung cancer It includes embodiments of the invention.

Expression of R11723 transcripts detectable by the amplicon shown in sequence name R11723seg13 in normal and cancerous lung tissues R11723seg13, R11723seg13 amplicon (SEQ ID NO: 1684) and R11723seg13F (SEQ ID NO: 1682) and R11723seg13R (SEQ ID NO: 1683) primers The expression of detectable transcripts was measured by real time PCR. In parallel, four housekeeping genes-PBGD (GenBank Accession No. BC019323, Amplicon – PBGD-Amplicon, SEQ ID No. 334), HPRT1 (GenBank Accession No. NM_000194, Amplicon – HPRT1- Amplicons, SEQ ID NO: 1297), SDHA (GenBank Accession No. NM_004168, Amplicon – SDHA-Amplicon SEQ ID NO: 331), and Ubiquitin (GenBank Accession No. BC000449, Amplicon – Ubiquitin-Amplicon The expression of SEQ ID NO: 328) was similarly measured. For each RT sample, the expression of the amplicon was normalized to the geometric mean of the housekeeping gene dose. The normalized amount of each RT sample is the center of the amount of normal postmortem (PM) samples (sample numbers 47-50, 90-93, 96-99 above, Table 2, "tissue samples in the test panel") Divide by the value to obtain the magnification of the upregulation of each sample relative to the median of normal PM samples.

  FIG. 48 is a histogram showing the overexpression of the transcript in cancerous lung samples compared to normal samples. The number and proportion of samples showing overexpression of at least 5 times of the total number of test samples are shown below.

  As apparent from FIG. 48, the expression of transcripts detectable by the above amplicon in a cancer sample was detected in non-cancerous samples (sample numbers 47 to 50, 90 to 93, 96 to 99, Table 2, “test panel Tissue samples in ') were higher. Apparently, at least 5-fold overexpression was found in 10 out of 15 adenocarcinoma samples and 4 out of 8 small cell carcinoma samples.

  Primer pairs are also optionally and preferably included within the scope of the present invention, for example, in the above experiments the following primers were used only as a non-limiting illustration of suitable primer pairs: R11723seg13F forward primer and R11723seg13R reverse Direction primer.

  The present invention also preferably includes any amplicon obtained by use of any suitable primer pair (e.g. in the above experiments) and obtained the following amplicons only as a non-limiting illustration of a suitable amplicon : R11723 seg13.

R11723seg13F (SEQ ID NO: 1682)-ACACTAAAACAACAAACACCTTGCTC
R11723 seg 13 R (SEQ ID NO: 1683)-TCCTCAGAAGGCACATGAAAGA
R11723seg13 – amplicon (SEQ ID NO: 1684):
ACACTAAAACAAAACACCTTGCTCTCTCGAGATGAGACATTTTGCCAAGTCAGACTACTTTTCTAGAGAAGCAACTATCTCTTTCATGTGCCTTCTGAGGA

Expression of the detectable R11723 transcript by the amplicon shown in the sequence name R11723seg13 in different normal tissues R11723seg13 amplicon (SEQ ID NO: 1684) and R11723 seg13F (SEQ ID NO: 1682) and R11723 seg13 R (SEQ ID NO: 1683) detectable transcript Expression was measured by real time PCR. In parallel, four housekeeping genes-RPL19 (GenBank Accession No. NM_000981, RPL19 amplicon, SEQ ID No. 1630), TATA box (GenBank Accession No. NM_003194, TATA amplicon, SEQ ID No. 1633), UBC (GenBank Accession The expression of No. BC000449, Amplicon – Ubiquitin-Amplicon, SEQ ID NO: 328), and SDHA (GenBank Accession No. NM_004168, Amplicon – SDHA-Amplicon SEQ ID NO: 331) was similarly measured. For each RT sample, the expression of the amplicon was normalized to the geometric mean of the housekeeping gene dose. Divide the normalized amount of each RT sample by the median of the amount of ovaries (samples 18-20 above, Table 2, "Tissue samples in the normal panel"), and compare each to the median of the ovaries The value of relative expression of was obtained.

R11723seg13F (SEQ ID NO: 1682)-ACACTAAAACAACAAACACCTTGCTC
R11723 seg 13 R (SEQ ID NO: 1683)-TCCTCAGAAGGCACATGAAAGA
R11723seg13 – amplicon (SEQ ID NO: 1684):
ACACTAAAACAAAACACCTTGCTCTCTCGAGATGAGACATTTTGCCAAGTCAGACTACTTTTCTAGAGAAGCAACTATCTCTTTCATGTGCCTTCTGAGGA

  The results are shown in FIG. 49, which shows the expression of R11723 transcript detectable by the amplicon shown in the sequence name R11723seg13 in different normal tissues.

Expression of R11723 transcripts detectable by the amplicon shown in the sequence name R11723junc11-18 in normal and cancerous lung tissue junc11-18, R11723junc11-18 amplicon (SEQ ID NO: 1687) and R11723junc11-18F (SEQ ID NO: 1685) and R11723junc11-18R (SEQ ID NO: 1686) Primer expression of transcripts detectable by real-time PCR was determined (this junction is a known protein sequence also referred to herein as PSEC sequence or "wild-type" ( WT) found in sequences). In parallel, four housekeeping genes-PBGD (GenBank Accession No. BC019323, Amplicon – PBGD-Amplicon, SEQ ID No. 334), HPRT1 (GenBank Accession No. NM_000194, Amplicon – HPRT1- Amplicons, SEQ ID NO: 1297), SDHA (GenBank Accession No. NM_004168, Amplicon – SDHA-Amplicon SEQ ID NO: 331), and Ubiquitin (GenBank Accession No. BC000449, Amplicon – Ubiquitin-Amplicon The expression of SEQ ID NO: 328) was similarly measured. For each RT sample, the expression of the amplicon was normalized to the geometric mean of the housekeeping gene dose. The normalized amount of each RT sample is that of the normal postmortem (PM) sample (sample numbers 47-50, 90-93, 96-99 above, Table 2, "Tissue samples in lung cancer test panel") The median was divided to obtain the upregulation of each sample relative to the median of normal PM samples.

  FIG. 50 is a histogram showing overexpression of the transcript in cancerous lung samples compared to normal samples. Values represent the average of duplicate experiments. Error bars indicate the obtained minimum and maximum values.

  As apparent from FIG. 50, the expression of transcripts detectable by the above amplicon in cancer samples was determined by non-cancerous samples (sample numbers 47-50, 90-93, 96-99, Table 2, “Lung cancer test Tissue samples in the panel "higher". Obviously, 11 out of 15 adenocarcinoma samples, 4 out of 16 squamous cell carcinoma samples, 1 out of 4 large cell carcinoma samples, 8 small cell carcinoma samples Overexpression of at least 5 fold was found in 5 of the

  Primer pairs are also optionally and preferably included within the scope of the present invention, for example, in the above experiments the following primers were used only as non-limiting examples of suitable primer pairs: R11723junc11-18F forward primer and R11723 junc11-18R reverse primer.

  The present invention also preferably includes any amplicon obtained by use of any suitable primer pair (e.g. in the above experiments) and obtained the following amplicons only as a non-limiting illustration of a suitable amplicon : R11723 junc 11-18.

R11723junc11-18F (SEQ ID NO: 1685) – AGTGATGGAGCAAAGTGCCG
R11723 junc11-18R (SEQ ID NO: 1686)-CAGCAGCTGATGCAAAACTGAG
R11723 junc11-18 – amplicon (SEQ ID NO: 1687)
AGTGATGGAGCAAGTGCCGGGATCATGTACCGCAAGTCCCTGTGCATCATCAGCGGCCTGTCTCATCGCCTGCTCTGCCGGTGACCAGTCCCTTGCTCCCCAGGGAAACTGAACTCAGTTTGCATCAGCTGCTG

Expression of R11723 transcript detectable by an amplicon as shown in sequence name R11723 junc11-18 in different normal tissues R11723 seg13 amplicon (SEQ ID NO: 1687) and R11723 junc11-18F (SEQ ID NO: 1685) and R11723 junc11-18R (SEQ ID NO: 1686) The expression of R11723 transcripts detectable by R was measured by real-time PCR. In parallel, four housekeeping genes-RPL19 (GenBank Accession No. NM_000981, RPL19 amplicon, SEQ ID No. 1630), TATA box (GenBank Accession No. NM_003194, TATA amplicon, SEQ ID No. 1633), UBC (GenBank Accession The expression of No. BC000449, Amplicon – Ubiquitin-Amplicon, SEQ ID NO: 328), and SDHA (GenBank Accession No. NM_004168, Amplicon – SDHA-Amplicon SEQ ID NO: 331) was similarly measured. For each RT sample, the expression of the amplicon was normalized to the geometric mean of the housekeeping gene dose. The normalized amount of each RT sample was divided by the median of the amounts of ovary samples (sample numbers 18-20 above, Table 3) to obtain the value of the relative expression of each sample relative to the median of the ovary samples.

R11723junc11-18F (SEQ ID NO: 1685) – AGTGATGGAGCAAAGTGCCG
R11723 junc11-18R (SEQ ID NO: 1686)-CAGCAGCTGATGCAAAACTGAG
R11723 junc11-18 – amplicon (SEQ ID NO: 1687)

AGTGATGGAGCAAGTGCCGGGATCATGTACCGCAAGTCCCTGTGCATCATCAGCGGCCTGTCTCATCGCCTGCTCTGCCGGTGACCAGTCCCTTGCTCCCCAGGGAAACTGAACTCAGTTTGCATCAGCTGCTG

  The results are shown in FIG. 73 and show the expression of R11723 transcripts detectable by the amplicon shown in the sequence name R11723junc11-18 in different normal tissues.

Preparation of Full-Length Validation RNAs for this Variant A human adult papillary adenocarcinoma ovarian RNA pool (Lot # ILS 1408) was obtained from ABS (http: //www.absbioreagents, Wilmington, DE 19801, USA com). Total RNA samples were processed using DNase I (Ambion catalog # 1906).

RT PCR
Preparation of RT Purified RNA (1 μg) was prepared using 150 ng Random Hexamer primer (Invitrogen Catalog No. 48190-011) and 500 μM dNTP (Takara, Catalog No. B9501-1), and a total of 15.6 μl of DEPC-H ₂ O (Beit Haemek) , Catalog No. 01-852-1A). The mixture was incubated at 65 ° C. for 5 minutes and cooled rapidly on ice. Then add 5 μl of 5 × Superscript II first strand buffer (Invitrogen, catalog number Y00146), 2.4 μl 0.1 M DTT (Invitrogen, catalog number Y00147), and 40 units of RNasin (Promega, catalog number N251A) The mixture was incubated at 42 ° C. for 2 minutes. Thereafter, 1 μl (200 units) of Superscript II (Invitrogen, Cat. No. 18064-022) was added, and the reaction was incubated for 50 minutes at 42 ° C. and then for 15 minutes at 70 ° C. The cDNA obtained was diluted 20 fold with TE buffer (10 mM Tris (pH = 8), 1 mM EDTA (pH = 8).

PCR amplification and analysis cDNA (5 μl) prepared as described above was used as a template for PCR reactions. Amplification was performed using AccuPower PCR PreMix (Bioneer, Korea, Catalog No. K2016) under the following conditions. 1 μl of the following primers (10 μM):
PSECfor-TGCTGTCGCCTCCTCTGATG
PSECrev-CCTCAGAAGGCACATGAAAG
+13 μl – H ₂ O was added to the AccuPower PCR PreMix tube and the following reaction program was used: 5 minutes at 94 ° C (30 seconds at 94 ° C, 30 seconds at 52 ° C, 40 seconds at 72 ° C) For 35 cycles, 72 ° C for 10 minutes. After completion of the PCR amplification, the products were stained with ethidium bromide and analyzed for UV light visualized agarose gel. The PCR products were extracted from the gel using the QiaQuickTM gel extraction kit (QiagenTM, catalog number 28706). The extracted DNA product (FIG. 79) was sequenced by direct sequencing using the gene specific primers (Hy-Labs, Israel) described above to obtain the deduced sequence of PSEC mutant R11723_PEA_1 T5 (FIG. 80) .

  As shown in FIG. 79, it was concluded that the putative PSEC mutant R11723_PEA_1 T5 was indeed naturally expressed in adult papillary adenoma ovarian human tissue.

Cloning of PSEC Mutant R11723_PEA_1 T5 in a Bacterial Expression Vector PSEC Splice Variant R11723_PEA_1 T5 Coding Sequence for PCR Amplification Using the Fragment Above and Platinum Pfx DNA Polymerase (Invitrogen Catalog No. 11708021) as a Template under the Following Conditions Amplification X10 buffer (Invitrogen Catalog No. 11708021); 2 μl – PCR product of the above; 1 μl – dNTP (10 mM each); 1 μl MgSO4 (50 mM) , 5 μl enhancer solution (Invitrogen Cat. No. 11708021); 33 μl – H 2 O; 1 μl of each primer (10 μM), and 1.25 units of Taq polymerase (Platinum Pfx DNA polymerase (Invitrogen Cat. No. 11708021)) for 3 minutes at 94 ° C (30 seconds at 94 ° C, 30 seconds at 58 ° C, 40 seconds at 68 ° C) For 29 cycles, 68 ° C. for 7 minutes. The following primers contain the specific sequence of the nucleotide sequence corresponding to the splice variant and the NheI and HindIII restriction sites.

PSEC NheI for-ATAGCTAGCATGTGGGTCCTAGGCATCGCGG
PSEC HindIII rev-CCCAAGCTCTTAATGTGTCAACTGCTTGGC

  The PCR product was then double digested with NheI and HindIII (New England Biolabs (UK) LTD) (FIG. 81), and pRSET-A pre-digested with the above enzymes in frame against the N-terminal 6His tag. HisPSEC T5 pRSET was obtained by insertion into Invitrogen, Cat. No. V 351-20) (FIG. 82). The coding sequence carries a 6His (6His residue is contiguous to one end of the protein) tag at the N-terminus and encodes a protein with 8 additional amino acids encoded by the pRSET vector.

  The sequences of the PSEC insert and its flanking regions in the final plasmid were verified by sequencing and found to be identical to the desired sequence. The complete sequence of His PSEC T5 pRESTA containing the sequenced region is shown in FIG.

Figure 83 shows the translated sequence of PSEC mutant R11723_PEA_1 T5.

Bacterial culture and induction of protein expression HisPSEC pRSETA DNA was transformed into intact DH5a cells (Invitrogen cat # 18258-012). Ampicillin resistant transformants were screened and positive clones were further analyzed by restriction enzyme digestion and sequence verification.

  To express the recombinant protein, HisPSEC pRSETA DNA was further transformed into competent BL21 Gold cells (Stratagene catalog no. 230134) and BL21 star (Invitrogen catalog no. 44-0054). Ampicillin resistant transformants were screened and positive clones were selected.

  Bacterial cells containing the HisPSEC T5 pRSET vector and the empty pRSET vector (as a negative control) were transformed into O. coli in LB medium supplemented with ampicillin (50 μg / ml) and chloramphenicol (34 μg / ml). D. It was grown until 600 nm reached 0.55. It reached this value in about 3 hours. 1 mM IPTG (Roche, Cat. No. 724815) was added and cells were grown overnight at 37 ° C. For gel analysis, 1 ml aliquots of each culture were removed after 0 hours, 3 hours incubation, and after overnight incubation (T0, T3, and TO / N, respectively).

Results of Expression The time course of the small expression of PSEC in BL21 Gold is shown in FIG. Expression of recombinant proteins of appropriate molecular weight (9.2 kDa) was visualized by Western blot using anti-His antibody (BD Clontech, Ref 631212, FIG. 85) but without Coomassie staining (data not shown) . Similar expression patterns were obtained using BL21 star as well (data not shown).

  These results indicate that the protein encoded by PSEC mutant R11723_PEA_1 T5 is indeed expressed in bacterial cells.

Description of Cluster R16276 Cluster R16276 features one transcript and five segments of interest, the names of which are shown in Tables 1305 and 1306, respectively, and the sequence itself is shown at the end of the application. Selected protein variants are shown in Table 1307.

  These sequences are also known as NOV protein homologue precursors (SwissProt accession identifier NOV_HUMAN, synonym NovH, nephroblastoma over-expressing gene protein homolog, which is a known protein, previously known herein as a protein) (SEQ ID NO: 1463).

  Protein NOV Protein homolog precursors are known or considered to have the following functions: Immediate-type proteins (by similarity) that are likely to play a role in cell growth control. The sequence of the protein NOV protein homologue precursor is shown at the end of the application as "NOV protein homologue precursor amino acid sequence". Known polymorphisms of this sequence are shown in Table 1308.

  The localization of the protein NOV protein homologue precursor is considered to be secretion.

  The following GO annotation applies to previously known proteins. The following annotations were found: control of cell growth which is related to biological processes, insulin related growth factor binding which is an annotation related to molecular function, growth factors and related to cellular components Extracellular, annotated.

  GO assignments can be made at one or more http: // www. expasy. SwissProt / TremBl Protein knowledgebase available from ch / sprot / or http: // www. ncbi. nlm. nih. Depends on Locuslink available from gov / projects / LocusLink /.

  Cluster R16276 can be used as a diagnostic marker by overexpression of transcripts of this cluster in cancer. The expression of such transcripts in normal tissues is also shown by the method previously described. The terms “number” in the right column of the table and the number on the y-axis of FIG. 51 refer to the weighted expression of ESTs in each category as “ppm” Ratio of expression to expression of all ESTs).

  In general, as shown for the histograms in FIG. 51 and Table 1309, the following results were obtained. This cluster was overexpressed (at least at minimal levels) in the following pathological conditions: malignant lung tumors.

  As mentioned above, cluster R16276 is characterized by one transcript as listed in Table 1 above. These transcripts encode proteins that are variants of the protein NOV protein homolog precursor. A description of each mutein of the invention is provided herein.

  The mutein R16276_PEA_1_P7 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript R16276_PEA_1_T6. An alignment to a known protein (NOV protein homologue precursor) is shown at the end of the application. One or more alignments to one or more previously published protein sequences are shown at the end of the application. A brief description of the relationship between the mutein of the present invention and each such aligned protein is as follows.

Report of comparison between R16276_PEA_1_P7 and NOV_HUMAN 1. The first amino acid sequence corresponding to amino acids 1 to 41 of NOV_HUMAN and corresponding to amino acids 1 to 41 of R16276_PEA_1_P7 with MQSV QSTSFCLRK QCLCLTLCLLLLLG LG. CPATPPTCAPVRAVLDGCSCCLVCARGSGCSDLEPCDESSGLYCDRADPSLYCLY corresponding to amino acids 43-103 of R16276_PEA_1_P7 and a second amino acid sequence at least 90% homologous to ADPSN QTGICT, and sequence GNPAP corresponding to amino acids 104-111 of R16276_PEA_1_P7 A third amino acid sequence which is at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95% homologous to a polypeptide having AV, said third An isolated chimeric polypeptide encoding R16276_PEA_1_P7, wherein the amino acid sequence of 1, the bridging amino acid, the second amino acid sequence, and the third amino acid sequence are adjacent and in sequential order.

  2. Of R16276_PEA_1_P7 comprising a polypeptide which is at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the sequence GNPAPSAV in R16276_PEA_1_P7 An isolated polypeptide encoding a tail.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein R16276_PEA_1_P7 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, enumerating other amino acids, and the last column shows SNPs as shown in Table 1312) It indicates whether it is known and the presence of a known SNP in the mutein R16276_PEA_1_P7 sequence supports the putative sequence of this mutein of the invention).

  The glycosylation sites of mutant protein R16276_PEA_1_P7 compared to known protein NOV protein homolog precursors are shown in Table 1314 (showing its position on the amino acid sequence in the first column, the second column has mutations in glycosylation sites) The presence or absence in the protein is indicated and the last column indicates whether this position is different on the mutated protein).

  The mutein R16276_PEA_1_P7 is encoded by the following transcript: R16276_PEA_1_T6 (sequences shown at the end of the application). The code portion of the transcript R16276_PEA_1_T6 is shown in bold, starting from position 445 and ending at position 777. The transcript also has the following SNPs listed in Table 1315 (indicating its position on the nucleotide sequence, listing another nucleic acid, the last column indicating whether the SNP is known, mutein R16276_PEA_1_P7 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  As mentioned above, cluster R16276 is characterized by the five segments listed in Table 2 above, the sequence of which is shown at the end of the application. These segments are part of the nucleic acid sequence, which are of particular interest and are individually described herein. A description of each segment of the invention is provided herein.

  The segment cluster R16276_PEA_1_node_0 of the present invention is supported by 35 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R16276_PEA_1_T6. Table 1316 below describes the start and end positions of this segment on each transcript.

  The segment cluster R16276_PEA_1_node_6 of the present invention is supported by two libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R16276_PEA_1_T6. Table 1317 below describes the start and end positions of this segment on each transcript.

  According to an optional embodiment of the present invention, there is also provided a short segment associated with the above cluster. These segments are up to about 120 bp in length and are therefore included in the individual descriptions.

  The segment cluster R16276_PEA_1_node_1 of the present invention is supported by 37 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R16276_PEA_1_T6. Table 1318 below describes the start and end positions of this segment on each transcript.

  The segment cluster R16276_PEA_1_node_4 of the present invention is supported by 38 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R16276_PEA_1_T6. Table 1319 below describes the start and end positions of this segment on each transcript.

  The segment cluster R16276_PEA_1_node_5 of the present invention is supported by 37 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: R16276_PEA_1_T6. Table 1320 below describes the start and end positions of this segment on each transcript.

Mutated protein alignment against previously known proteins:
Sequence name: NOV_HUMAN

Sequence documentation:

Alignment of: R16276_PEA_1_P7 x NOV_HUMAN ..

Alignment segment 1/1:

Quality: 1042.00 Escore: 0
Matching length: 103 Total length: 103
Matching Percent Similarity: 100.00 Matching Percent Identity: 99.03
Total Percent Similarity: 100.00 Total Percent Identity: 99.03
Gaps: 0

Alignment:
....
1 MQSVQSTSFCLRKQCLCLTFLLLHLLGQVAATQRCPPQCPGQCTPPTTC 50
|||||||||||||||||||||||||||||||||: |||||||||
1 MQSVQSTSFCLRKQCLCLTFLLLHLLGQVAATQRCPPQCPRCPTPPTC 50
....
51 APGVRAVLDGCSCCLVCARGRGSESCDLEPCDESSGLYCDRSADPSNQTG 100
||||||||||||||||||||||||||||||||||||||||
51 APGVRAVLDGCSCCLVCARGRGSESCDLEPCDESSGLYCDRSADPSNQTG 100

101 ICT 103
||||
101 ICT 103

Combined expression of six sequences H61775seg8, HUMGRP5E junc3-7, M85491Seg24, Z21368junc17-21, HSSTROL3seg24, and Z25299seg20 in normal and cancerous lung tissue H61775seg8 (SEQ ID NO: 1636), HUMGRP5Ejunc3-7 (SEQ ID NO: 1648), M85491 Eg 1639), Z21368junc17-21 (SEQ ID NO: 1642), HSSTROL3seg24 (SEQ ID NO: 1675), and Z25299seg20 amplicon (SEQ ID NO: 1669) and H61775seg8F2 (SEQ ID NO: 1634), H61775seg8R2 (SEQ ID NO: 1635), HUMGRP5Ejunc3-7F (SEQ ID NO: 1616) 6) HUMGRP5Ejunc3-7R (SEQ ID NO: 1647), M85491 Seg24F (SEQ ID NO: 1637), M85491 Seg24R (SEQ ID NO: 1638), Z21368 junc17-21F (SEQ ID NO: 1640), Z21368 junc17-21R (SEQ ID NO: 1641), HSSTROL3seg24F (SEQ ID NO: 1673) , HSSTROL3seg24R (SEQ ID NO: 1674), Z25299seg20F (SEQ ID NO: 1667), Z25299seg20R (SEQ ID NO: 1668) Immunoglobulin superfamily member 9 detectable by the primer, Gastrin releasing peptide, Ephrin type B receptor 2 precursor, SUL1_HUMAN, stromelysin-3 Precursor (EC 3.4.24.-) (matrix metal powder The expression of rotinase-11) (MMP-11) (ST3) (SL-3) and acid stable proteinase inhibitor transcript which is a secreted leukocyte proteinase inhibitor was measured by real time PCR. In parallel, four housekeeping genes-PBGD (GenBank Accession No. BC019323, Amplicon – PBGD-Amplicon, SEQ ID No. 334), HPRT1 (GenBank Accession No. NM_000194, Amplicon – HPRT1- Amplicons, SEQ ID NO: 1297), Ubiquitin (GenBank Accession No. BC000449, Amplicon – Ubiquitin-Amplicon SEQ ID NO: 328), and SDHA (GenBank Accession No. NM_004168, Amplicon – SDHA-Amplicon The expression of SEQ ID NO: 331) was similarly measured. For each RT sample, the expression of the amplicon was normalized to the geometric mean of the housekeeping gene dose. Normalized postmortem (PM) samples detected for the same amplicon (Sample Nos. 47-50, 90-93, 96-99 above, Table 2, Test, Normalized Amount of each RT sample for each amplicon. The median of the amount of tissue samples in the panel ") was divided to obtain the upregulation of each sample relative to the median of normal PM samples. The reciprocal of this ratio for Z25299seg20 (SEQ ID NO: 1669) was calculated to obtain the downregulation of each sample relative to the median of normal PM samples.

  Figures 52-53 are histograms showing differential expression of the transcript in cancerous lung samples compared to normal samples. The numbers and proportions of samples showing at least 5 times the differential expression of at least one sequence out of the total number of samples tested are indicated below.

  As is apparent from FIGS. 52 to 53, 15 out of 15 adenocarcinoma samples, 14 out of 16 squamous cell carcinoma samples, 4 out of 4 large cell carcinoma samples, 8 A differential expression of at least 5 fold was found in at least one sequence of 8 of the small cell carcinoma samples.

  Statistical analysis was applied to verify the significance of these results as described below. The threshold for 5-fold differential control of at least one amplicon was found to be different between cancer and normal samples, and checked by Fisher's exact test, the P value was 7.82E- for adenocarcinoma. 06, 2.63E-04 in squamous cell carcinoma, 8.24E-03 in large cell carcinoma and 3.57E-04 in small cell carcinoma.

  The above values indicate that the results are statistically significant.

Description of cluster H53626 Cluster H53626 is characterized by two transcripts of interest and 20 segments, the names of which are shown in Tables 1321 and 1322 respectively, and the sequence itself is shown at the end of the application.

  Cluster H53626 can be used as a diagnostic marker by overexpression of transcripts of this cluster in cancer. The expression of such transcripts in normal tissues is also shown by the method previously described. The term "number" in the right column of the table and the number on the y-axis of Figure 76 below refer to the weighted expression of EST in each category as "ppm" (specific clusters in this category by ppm Ratio of EST expression to total EST expression).

  In general, as shown for the histograms in FIG. 76 and Table 1324, the following results were obtained. This cluster was overexpressed (at least at minimal levels) in the following pathological conditions: epithelial malignancies, a mixture of malignancies from different tissues, and myomas.

  As mentioned above, contig H53626 is characterized by the two transcripts listed in Table 1321 above. A description of each mutein of the invention is provided herein.

  The mutein H53626_PEA_1_P4 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript H53626_PEA_1_T15. An alignment to the wild type protein is shown at the end of the application. A brief description of the relationship between the mutein of the present invention and the wild-type protein is as follows.

Report of comparison between H53626_PEA_1_P4 and wild type Q8N441 (SEQ ID NO: 1699). Corresponding to amino acids 1 to 357 of Q8N441, corresponding to amino acids 1 to 357 of H53626_PEA_1_P4 MTPSPLLLLLLPPLLLGAFPPAAAARGPPKMADKVVPRQVARLGRTVRLQCPVEGDPPPLTMWTKDGRTIHSGWSRFRVLPQGLKVKQVEREDAGVYVCKATNGFGSLSVNYTLVVLDDISPGKESLGPDSSSGGQEDPASQQWARPRFTQPSKMRRRVIARPVGSSVRLKCVASGHPRPDITWMKDDQALTRPEAAEPRKKKWTLSLKNLRPEDSGKYTCRVSNRAGAINATYKVDVIQRTRSKPVLTGTHPVNTTVDFGGTTSFQCKVRSDVKPVIQWL A case in which a first amino acid sequence which is at least 90% homologous to HVE26GAEGHHNSTIDVGGQKFV VLPTGDVWSRPDSYNL KL ITRALQ DDAGLYCHGMGSFAFLTVLP and a sequence corresponding to amino acids 358 to 437 of H53626_PEA_1_P4 is used. Is a second amino acid sequence that is at least 90%, most preferably at least 95% homologous, and corresponds to amino acids 358 to 504 of Q8N441, The corresponding amino acids 438 to 584 of the 26_PEA_1_P4 are also corresponding to DPKPPV AVESSSATSLPWPVVIGIA GAVFILF LGLLLQAQKPCPCAPAPLPRPRPTARDRPDHADRPKLDLALSAGPGVGLCHEG HPGAPAGHT KHT LYTPHHTHTVHIVHQHQQHQ QHQ and a semiconductive metal sheet An isolated chimeric polypeptide encoding H53626_PEA_1_P4.

  2. A sequence corresponding to H53626_PEA_1_P4 that is at least 70%, optionally at least about 80%, preferably at least about 85%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the coding sequence An isolated polypeptide encoding the edge portion of H53626_PEA_1_P4 comprising.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: membrane. For protein localization, both signal peptide estimation programs agree that this protein has a signal peptide, but both transmembrane domain estimation programs predict that this protein has a transmembrane domain downstream of this signal peptide. It is considered to be a membrane.

  The mutein H53626_PEA_1_P4 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, listing other amino acids, and the last column shows SNPs as shown in Table 1326) It indicates whether it is known and the presence of a known SNP in the mutant protein H53626_PEA_1_P4 sequence supports the predicted sequence of this mutant protein of the invention).

  The mutein, H53626_PEA_1_P4, is encoded by the following transcript: H53626_PEA_1_T15 (sequences shown at the end of the application). The coding portion of transcript H53626_PEA_1_T15 is shown in bold and this coding portion starts at position 17 and ends at position 1771. The transcript also has the following SNPs listed in Table 1327 (showing its position on the nucleotide sequence and listing another nucleic acid, the last column shows whether the SNP is known, mutein H53626_PEA_1_P4 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  The mutein H53626_PEA_1_P5 of the invention has the amino acid sequence shown at the end of the application and is encoded by the transcript H53626_PEA_1_T16. An alignment to the wild type protein is shown at the end of the application. A brief description of the relationship between the mutein of the present invention and the wild-type protein is as follows.

Report of the comparison between H53626_PEA_1_P5 and wild type Q9H4D7 (SEQ ID NO: 1700). Corresponding to amino acids 1-269 of Q9H4D7, at least 90% homologous I and MTPSPLLLLLLPPLLLGAFPPAAAARGPPKMADKVVPRQVARLGRTVRLQCPVEGDPPPLTMWTKDGRTIHSGWSRFRVLPQGLKVKQVEREDAGVYVCKATNGFGSLSVNYTLVVLDDISPGKESLGPDSSSGGQEDPASQQWARPRFTQPSKMRRRVIARPVGSSVRLKCVASGHPRPDITWMKDDQALTRPEAAEPRKKKWTLSLKNLRPEDSGKYTCRVSNRAGAINATYKVDVIQRTRSKPVLTGTHPVNTTVDFGGTTSFQCK corresponding to amino acids 1-269 of H53626_PEA_1_P5 And 1 amino acid sequence, a polypeptide at least 70% with a sequence corresponding to TQNRQGHLWPPRPRPLACRGPWSSASQPALSSSWAPCSCGFARPRRSRAPPRLPLPCLGTARRGRPATAAETRTFPRWPPSALALVWGCVRSMGLRQPPSTYWAQAQLLALSCTPNSTQTSTHTHTHTLTHTHTWRARSTSTSTISARRHRICSGHGGAGQTGRLGGWRTELQTKAGDPWRGGMASTPGSLCVRHSPWTHTHRHTHYLDACMHTHARTRAP to amino acid 270-490 of H53626_PEA_1_P5, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most Mashiku comprises at least 95% homologous to a second amino acid sequence, wherein the first and second amino acid sequences are contiguous, and in sequential order, the isolated chimeric polypeptide coding H53626_PEA_1_P5.

  2. SEQ TQNRQGHLWPPRPRPLACRGPWSSASQPALSSSWAPCSCGFARPRRSRAPPRLPLPCLGTARRGRPATAAETRTFPRWPPSALALVWGCVRSMGLRQPPSTYWAQAQLLALSCTPNSTQTSTHTHTHTLTHTHTWRARSTSTSTISARRHRICSGHGGAGQTGRLGGWRTELQTKAGDPWRGGMASTPGSLCVRHSPWTHTHRHTHYLDACMHTHARTRAP at least 70% in H53626_PEA_1_P5, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the polypeptide, H53626 An isolated polypeptide encoded by a tail of PEA_1_P5.

Report of comparison between H53626_PEA_1_P5 and wild type Q8N441. Corresponding to amino acids 1-269 of Q8N441, at least 90% homologous I and MTPSPLLLLLLPPLLLGAFPPAAAARGPPKMADKVVPRQVARLGRTVRLQCPVEGDPPPLTMWTKDGRTIHSGWSRFRVLPQGLKVKQVEREDAGVYVCKATNGFGSLSVNYTLVVLDDISPGKESLGPDSSSGGQEDPASQQWARPRFTQPSKMRRRVIARPVGSSVRLKCVASGHPRPDITWMKDDQALTRPEAAEPRKKKWTLSLKNLRPEDSGKYTCRVSNRAGAINATYKVDVIQRTRSKPVLTGTHPVNTTVDFGGTTSFQCK corresponding to amino acids 1-269 of H53626_PEA_1_P5 And 1 amino acid sequence, a polypeptide at least 70% with a sequence corresponding to TQNRQGHLWPPRPRPLACRGPWSSASQPALSSSWAPCSCGFARPRRSRAPPRLPLPCLGTARRGRPATAAETRTFPRWPPSALALVWGCVRSMGLRQPPSTYWAQAQLLALSCTPNSTQTSTHTHTHTLTHTHTWRARSTSTSTISARRHRICSGHGGAGQTGRLGGWRTELQTKAGDPWRGGMASTPGSLCVRHSPWTHTHRHTHYLDACMHTHARTRAP to amino acid 270-490 of H53626_PEA_1_P5, optionally at least 80%, preferably at least 85%, more preferably at least 90%, most Mashiku comprises at least 95% homologous to a second amino acid sequence, wherein the first and second amino acid sequences are contiguous, and in sequential order, the isolated chimeric polypeptide coding H53626_PEA_1_P5.

  2. SEQ TQNRQGHLWPPRPRPLACRGPWSSASQPALSSSWAPCSCGFARPRRSRAPPRLPLPCLGTARRGRPATAAETRTFPRWPPSALALVWGCVRSMGLRQPPSTYWAQAQLLALSCTPNSTQTSTHTHTHTLTHTHTWRARSTSTSTISARRHRICSGHGGAGQTGRLGGWRTELQTKAGDPWRGGMASTPGSLCVRHSPWTHTHRHTHYLDACMHTHARTRAP at least 70% in H53626_PEA_1_P5, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90%, most preferably at least about 95% homologous to the polypeptide, H53626 An isolated polypeptide encoded by a tail of PEA_1_P5.

  The position of the mutein was determined according to the results from a number of different software programs and analyses, including analysis with SignalP and other specialized programs. The muteins are believed to be positioned with respect to the cells as follows: secretion. Protein localization is secreted because both signal peptide estimation programs predict that this protein has a signal peptide, and both transmembrane domain estimation programs predict that this protein has no transmembrane domain. It is thought that.

  The mutein H53626_PEA_1_P5 also has the following non-silent SNPs (single nucleotide polymorphisms) (showing its position on the amino acid sequence, enumerating other amino acids, and the last column shows SNPs as shown in Table 1328) It indicates whether it is known and the presence of a known SNP in the mutant protein H53626_PEA_1_P5 sequence supports the deduced sequence of this mutant protein according to the invention).

  The mutein, H53626_PEA_1_P5, is encoded by the following transcript: H53626_PEA_1_T16 (sequences shown at the end of the application). The coding portion of transcript H53626_PEA_1_T16 is shown in bold, starting at position 17 and ending at position 1489. The transcript also has the following SNPs listed in Table 1329 (showing its position on the nucleotide sequence and listing another nucleic acid, the last column shows whether the SNP is known, mutein H53626_PEA_1_P5 The presence of known SNPs in the sequence supports the deduced sequence of this mutein of the invention).

  As mentioned above, cluster H53626 is characterized by the 20 segments listed in Table 2 above, the sequence of which is shown at the end of the application. These segments are part of the nucleic acid sequence, which are of particular interest and are individually described herein. A description of each segment of the invention is provided herein.

  The segment cluster H53626_PEA_1_node_15 of the present invention is supported by 25 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: H53626_PEA_1_T15 and H53626_PEA_1_T16. Table 1330 below describes the start and end positions of this segment on each transcript.

  The segment cluster H53626_PEA_1_node_22 of the present invention is supported by 42 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: H53626_PEA_1_T15 and H53626_PEA_1_T16. Table 1332 below describes the start and end positions of this segment on each transcript.

  The segment cluster H53626_PEA_1_node_25 of the present invention is supported by 41 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: H53626_PEA_1_T15. Table 1334 below describes the start and end positions of this segment on each transcript.

  The segment cluster H53626_PEA_1_node_26 of the present invention is supported by 5 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: H53626_PEA_1_T15. Table 1336 below describes the start and end positions of this segment on each transcript.

  The segment cluster H53626_PEA_1_node_27 of the present invention is supported by 106 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: H53626_PEA_1_T15 and H53626_PEA_1_T16. Table 1338 below describes the start and end positions of this segment on each transcript.

  The segment cluster H53626_PEA_1_node_34 of the present invention is supported by 121 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: H53626_PEA_1_T15 and H53626_PEA_1_T16. Table 1340 below describes the start and end positions of this segment on each transcript.

  The segment cluster H53626_PEA_1_node_35 of the present invention is supported by 85 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: H53626_PEA_1_T15 and H53626_PEA_1_T16. Table 1342 below describes the start and end positions of this segment on each transcript.

  Microarray (chip) data for this segment is also available, as follows. As described above, with respect to the clusters themselves, different oligonucleotides were tested for differential expression in different disease states, in particular cancer. The following oligonucleotides were found to reach this segment (shown in Table 1343).

  The segment cluster H53626_PEA_1_node_36 of the present invention is supported by 69 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: H53626_PEA_1_T15 and H53626_PEA_1_T16. Table 1344 below describes the start and end positions of this segment on each transcript.

  Microarray (chip) data for this segment is also available, as follows. As described above, with respect to the clusters themselves, different oligonucleotides were tested for differential expression in different disease states, in particular cancer. The following oligonucleotides were found to reach this segment (shown in Table 13455).

  According to an optional embodiment of the present invention, there is also provided a short segment associated with the above cluster. These segments are up to about 120 bp in length and are therefore included in the individual descriptions.

  The segment cluster H53626_PEA_1_node_11 of the present invention is supported by 12 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: H53626_PEA_1_T15 and H53626_PEA_1_T16. Table 1346 below describes the start and end positions of this segment on each transcript.

  The segment cluster H53626_PEA_1_node_12 of the present invention is supported by 11 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: H53626_PEA_1_T15 and H53626_PEA_1_T16. Table 1347 below describes the start and end positions of this segment on each transcript.

  The segment cluster H53626_PEA_1_node_16 according to the invention can be found in the following transcript: H53626_PEA_1_T15 and H53626_PEA_1_T16. Table 1348 below describes the start and end positions of this segment on each transcript.

  The segment cluster H53626_PEA_1_node_19 of the present invention is supported by 25 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: H53626_PEA_1_T15 and H53626_PEA_1_T16. Table 1349 below describes the start and end positions of this segment on each transcript.

  The segment cluster H53626_PEA_1_node_20 of the present invention is supported by 27 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: H53626_PEA_1_T15 and H53626_PEA_1_T16. Table 1350 below describes the start and end positions of this segment on each transcript.

  The segment cluster H53626_PEA_1_node_24 of the present invention is supported by 34 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: H53626_PEA_1_T15 and H53626_PEA_1_T16. Table 1351 below describes the start and end positions of this segment on each transcript.

  The segment cluster H53626_PEA_1_node_28 of the present invention is supported by 66 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: H53626_PEA_1_T15 and H53626_PEA_1_T16. Table 1352 below describes the start and end positions of this segment on each transcript.

  The segment cluster H53626_PEA_1_node_29 of the present invention is supported by 73 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: H53626_PEA_1_T15 and H53626_PEA_1_T16. Table 1353 below describes the start and end positions of this segment on each transcript.

  The segment cluster H53626_PEA_1_node_30 of the present invention is supported by 71 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: H53626_PEA_1_T15 and H53626_PEA_1_T16. Table 1354 below describes the start and end positions of this segment on each transcript.

  The segment cluster H53626_PEA_1_node_31 of the present invention is supported by 67 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: H53626_PEA_1_T15 and H53626_PEA_1_T16. Table 1355 below describes the start and end positions of this segment on each transcript.

  The segment cluster H53626_PEA_1_node_32 of the present invention is supported by 65 libraries. The number of libraries was determined as described above. This segment can be found in the following transcript: H53626_PEA_1_T15 and H53626_PEA_1_T16. Table 1356 below describes the start and end positions of this segment on each transcript.

  The segment cluster H53626_PEA_1_node_33 according to the invention can be found in the transcript: H53626_PEA_1_T15 and H53626_PEA_1_T16. Table 1357 below describes the start and end positions of this segment on each transcript.

Mutated protein alignment against previously known proteins:
Sequence name: / tmp / K1Mec2ReKO / eg1EUS2AXY: Q8N441

Sequence documentation:

Alignment of: H53626_PEA_1_P4 x Q8N441 ..

Alignment segment 1/1:

Quality: 4882.00 Escore: 0
Matching length: 504 Total length: 584
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 86.30 Total Percent Identity: 86.30
Gaps: 1

Alignment:
....
1 MTPSPLLLLLLPPLLLGAFPPAAAARGPPKMADKV VPRQ VARLGRTVRLQ 50
||||||||||||||||||||||||||||||||||||||||
1 MTPSPLLLLLLPPLLLGAFPPAAAARGPPKMADKV VPRQ VARLGRTVRLQ 50
....
51 CPVEGDPPPLTTM WT KTDGRTIHSGWSRFRVLPQGLKVKQVEREDAGVYVCK 100
||||||||||||||||||||||||||||||||||||||||
51 CPVEGDPPPLTTM WT KTDGRTIHSGWSRFRVLPQGLKVKQVEREDAGVYVCK 100
....
101 ATNGFGSLSVNYTLVVLDDISPGKESLGPDSSSGGQEDPASQQWARPRFT 150
||||||||||||||||||||||||||||||||||||||||
101 ATNGFGSLSVNYTLVVLDDISPGKESLGPDSSSGGQEDPASQQWARPRFT 150
....
151 QPSKMRRRVIARPVGSSVRLKCVASGHPRPDITWMKDDQALTRPEAAEPR 200
||||||||||||||||||||||||||||||||||||||||
151 QPSKMRRRVIARPVGSSVRLKCVASGHPRPDITWMKDDQALTRPEAAEPR 200
....
201 KKKWTLSLKNLRPEDSGKYTCRVSNRAGAINATYKVDVIQRTRSKPVLTG 250
||||||||||||||||||||||||||||||||||||||||
201 KKKWTLSLKNLRPEDSGKYTCRVSNRAGAINATYKVDVIQRTRSKPVLTG 250
....
251 THPVNTTVDFGGGGTTSFQCKVRSDV KPVIQWLKRVEYGAEGRHNSTIDVGG 300
||||||||||||||||||||||||||||||||||||||||
251 THPVNTTVDFGGGGTTSFQCKVRSDV KPVIQWLKRVEYGAEGRHNSTIDVGG 300
....
301 QKFVLPTGDVWSRPDGSYLNKL LITRARQDDAGMYICLGANTMGYSFRS 350
||||||||||||||||||||||||||||||||||||||||
301 QKFVLPTGDVWSRPDGSYLNKL LITRARQDDAGMYICLGANTMGYSFRS 350
....
351 AFLTVLPGARLPRHATPCWCDPPPPPGPGPPPPTGWGPTSLAVLARSAE 400
||||||||
351 AFLTVLP ........................................ 357
....
401 GGQPRTGTVSTAPGMGGCSPGLCVGVPLPTSPPLADPKPPGPPVASSS 450
||||||||||||
358 ......................................... DPKPPGPPVASSS 370
....
451 SATSLPWPPVVIGIPAGAVFILGTLLWLCQAQKKPCTPAPAPPLPHRPP 500
||||||||||||||||||||||||||||||||||||||||
371 SATSLPWPVVIGIGAVFILFILTLLLWLCQAQKKPCTPAPAPPLPHRPP 420
....
501 GTARDRSGDKDLPSALSAGPGVGLCEEHGSPA APQ HLLGPGPVAGPKL 550
||||||||||||||||||||||||||||||||||||||||
421 GTARDRSGDKDLPSALSAGPGVGLCEEHGSPA APQ HLLGPGPVAGPKL 470
....
551 YPKLYTDIHTHTHTHTHSHTHSHVEGKVHQHIHYQC 584
|||||||||||||||||||||||||||||||
471 YPKLYTDIHTHTHTHTHTHTHSHVEGKVHQHIHYQC 504






Sequence name: / tmp / oSUZaRW3WK / oSh3fN5Zt0: Q9H4D7

Sequence documentation:

Alignment of: H53626_PEA_1_P5 x Q9H4D7 ..

Alignment segment 1/1:

Quality: 2644.00 Escore: 0
Matching length: 269 Total length: 269
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MTPSPLLLLLLPPLLLGAFPPAAAARGPPKMADKV VPRQ VARLGRTVRLQ 50
||||||||||||||||||||||||||||||||||||||||
1 MTPSPLLLLLLPPLLLGAFPPAAAARGPPKMADKV VPRQ VARLGRTVRLQ 50
....
51 CPVEGDPPPLTTM WT KTDGRTIHSGWSRFRVLPQGLKVKQVEREDAGVYVCK 100
||||||||||||||||||||||||||||||||||||||||
51 CPVEGDPPPLTTM WT KTDGRTIHSGWSRFRVLPQGLKVKQVEREDAGVYVCK 100
....
101 ATNGFGSLSVNYTLVVLDDISPGKESLGPDSSSGGQEDPASQQWARPRFT 150
||||||||||||||||||||||||||||||||||||||||
101 ATNGFGSLSVNYTLVVLDDISPGKESLGPDSSSGGQEDPASQQWARPRFT 150
....
151 QPSKMRRRVIARPVGSSVRLKCVASGHPRPDITWMKDDQALTRPEAAEPR 200
||||||||||||||||||||||||||||||||||||||||
151 QPSKMRRRVIARPVGSSVRLKCVASGHPRPDITWMKDDQALTRPEAAEPR 200
....
201 KKKWTLSLKNLRPEDSGKYTCRVSNRAGAINATYKVDVIQRTRSKPVLTG 250
||||||||||||||||||||||||||||||||||||||||
201 KKKWTLSLKNLRPEDSGKYTCRVSNRAGAINATYKVDVIQRTRSKPVLTG 250
.
251 THPVNTTVDFGGGGTTSFQCK 269
||||||||||||||||||
251 THPVNTTVDFGGGGTTSFQCK 269






Sequence name: / tmp / oSUZaRW3WK / oSh3fN5Zt0: Q8N441

Sequence documentation:

Alignment of: H53626_PEA_1_P5 x Q8N441 ..

Alignment segment 1/1:

Quality: 2644.00 Escore: 0
Matching length: 269 Total length: 269
Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:
....
1 MTPSPLLLLLLPPLLLGAFPPAAAARGPPKMADKV VPRQ VARLGRTVRLQ 50
||||||||||||||||||||||||||||||||||||||||
1 MTPSPLLLLLLPPLLLGAFPPAAAARGPPKMADKV VPRQ VARLGRTVRLQ 50
....
51 CPVEGDPPPLTTM WT KTDGRTIHSGWSRFRVLPQGLKVKQVEREDAGVYVCK 100
||||||||||||||||||||||||||||||||||||||||
51 CPVEGDPPPLTTM WT KTDGRTIHSGWSRFRVLPQGLKVKQVEREDAGVYVCK 100
....
101 ATNGFGSLSVNYTLVVLDDISPGKESLGPDSSSGGQEDPASQQWARPRFT 150
||||||||||||||||||||||||||||||||||||||||
101 ATNGFGSLSVNYTLVVLDDISPGKESLGPDSSSGGQEDPASQQWARPRFT 150
....
151 QPSKMRRRVIARPVGSSVRLKCVASGHPRPDITWMKDDQALTRPEAAEPR 200
||||||||||||||||||||||||||||||||||||||||
151 QPSKMRRRVIARPVGSSVRLKCVASGHPRPDITWMKDDQALTRPEAAEPR 200
....
201 KKKWTLSLKNLRPEDSGKYTCRVSNRAGAINATYKVDVIQRTRSKPVLTG 250
||||||||||||||||||||||||||||||||||||||||
201 KKKWTLSLKNLRPEDSGKYTCRVSNRAGAINATYKVDVIQRTRSKPVLTG 250
.
251 THPVNTTVDFGGGGTTSFQCK 269
||||||||||||||||||
251 THPVNTTVDFGGGGTTSFQCK 269

Expression of homo-Sapiens fibroblast growth factor receptor-like 1 (FGFRL1) H53626 transcripts detectable by an amplicon as shown in sequence name H53626junc24-27F1R3 in normal and cancerous lung tissue junc24-27, H53626junc24-27F1R3 amplicon (SEQ ID NO: 1690) and H53626 junc24-27F1 (SEQ ID NO: 1688) and H53626 junc24-27R3 (SEQ ID NO: 1689) The expression of Homo sapiens fibroblast growth factor receptor like 1 (FGFRL1) transcripts detectable by primers Measured by time PCR. In parallel, four housekeeping genes-PBGD (GenBank Accession No. BC019323, Amplicon – PBGD-Amplicon, SEQ ID No. 334), HPRT1 (GenBank Accession No. NM_000194, Amplicon – HPRT1- Amplicons, SEQ ID NO: 1297), UBC (GenBank Accession No. BC000449, Amplicon – Ubiquitin-Amplicon SEQ ID NO: 328), and SDHA (GenBank Accession No. NM_004168, Amplicon – SDHA-Amplicon The expression of SEQ ID NO: 331) was similarly measured. For each RT sample, the expression of the amplicon was normalized to the geometric mean of the housekeeping gene dose. Normalized PM samples by dividing the normalized volume of each RT sample by the median volume of normal postmortem (PM) samples (sample numbers 47-50, 90-93, 96-99, Table 2 above) Magnifications of upregulation of each sample to the median of were obtained.

  FIG. 74 is a histogram showing over expression of the homo-Sapiens fibroblast growth factor receptor-like 1 (FGFRL1) transcript in cancerous lung samples as compared to normal samples.

    As apparent from FIG. 74, the expression of homo-Sapiens fibroblast growth factor receptor-like 1 (FGFRL1) transcripts detectable by the above amplicon in several cancer samples is a non-cancerous sample (sample number) 46-50, 90-93, 96-99, higher than Table 2). Apparently, at least 5-fold overexpression was found in 7 out of 15 adenocarcinoma samples.

  Primer pairs are also optionally and preferably included within the scope of the present invention, for example, in the above experiments the following primers were used only as non-limiting examples of suitable primer pairs: H53626junc24-27F1 forward primer and H53626 junc24-27R3 reverse primer.

  The present invention also preferably includes any amplicon obtained by use of any suitable primer pair (e.g. in the above experiments) and obtained the following amplicons only as a non-limiting illustration of a suitable amplicon : H5326 junc24-27F1R3.

Forward primer (SEQ ID NO: 1688): GTCCTTCCAGTGCAAGACCCA
Reverse primer (SEQ ID NO: 1689): TGGGCCTGGCAAAGCC
Amplicon (SEQ ID NO: 1690): GTCCTTCCAGTGCAAGACCCAAAACCGCCAGGGCCACCTGTGGCCTCCTCGTCCTCGGCCACTAGCCTGTCCGTGTGGCCCTGTGCATCGGCATCCCAGCCGGGCGCTGTCTTCATGGTCACCTGTCCTGGTCTGTCTGCCAGTGCCA

Expression of homo-Sapiens fibroblast growth factor receptor-like 1 (FGFRL1) H53626 transcripts detectable by an amplicon shown in sequence name H53626seg25 in normal and cancerous lung tissue seg25, H53626seg25 amplicon (SEQ ID NO: 1693), The expression of homo-Sapiens fibroblast growth factor receptor-like 1 (FGFRL1) transcripts detectable by H53626seg25F (SEQ ID NO: 1691) and H53626seg25R (SEQ ID NO: 1692) primers was measured by real-time PCR. In parallel, four housekeeping genes-PBGD (GenBank Accession No. BC019323, Amplicon – PBGD-Amplicon, SEQ ID No. 334), HPRT1 (GenBank Accession No. NM_000194, Amplicon – HPRT1- Amplicons, SEQ ID NO: 1297), UBC (GenBank Accession No. BC000449, Amplicon – Ubiquitin-Amplicon SEQ ID NO: 328), and SDHA (GenBank Accession No. NM_004168, Amplicon – SDHA-Amplicon The expression of SEQ ID NO: 331) was similarly measured. For each RT sample, the expression of the amplicon was normalized to the geometric mean of the housekeeping gene dose. Normalized PM samples by dividing the normalized volume of each RT sample by the median volume of normal postmortem (PM) samples (sample numbers 47-50, 90-93, 96-99, Table 2 above) Magnifications of upregulation of each sample to the median of were obtained.

  As evident from FIG. 75, the expression of homo-Sapiens fibroblast growth factor receptor-like 1 (FGFRL1) transcripts detectable by the above amplicon in several cancer samples is a non-cancerous sample (sample number) 46-50, 90-93, 96-99, higher than Table 2). Apparently, at least 5-fold overexpression was found in 3 out of 15 adenocarcinoma samples.

  Primer pairs are also optionally and preferably included within the scope of the present invention, for example, in the above experiments the following primers were used only as non-limiting examples of suitable primer pairs: H53626seg25F forward primer and H53626seg25R reverse Direction primer.

  The present invention also preferably includes any amplicon obtained by use of any suitable primer pair (e.g. in the above experiments) and obtained the following amplicons only as a non-limiting illustration of a suitable amplicon : H53626 seg 25.

Forward primer (SEQ ID NO: 1691); CCGACGGCTCCTACTCCAA
Reverse primer (SEQ ID NO: 1692): GGAAGCTGTAGCCCATGGTGT
Reverse primer (SEQ ID NO: 1693): CCGACGGCTCCTACTCCATAAAAGCTGCTCATACCCGTGCCCGCCCAGGACGATGCGGGCATGTACATCTGCCTTGGCGCCAAACACCATGGGCTAAGCTTCTC

Expression of homo-Sapiens fibroblast growth factor receptor-like 1 (FGFRL1) H53626 transcripts detectable by an amplicon shown in the sequence name H53626seg25 in different normal tissues H53626seg25 amplicon (SEQ ID NO: 1693) as well as H53626seg25F (SEQ ID NO: 1691) ) And the expression of homo-Sapiens fibroblast growth factor receptor-like 1 (FGFRL1) transcripts detectable by H53626 seg 25 R (SEQ ID NO: 1692) primers was measured by real-time PCR. In parallel, four housekeeping genes-RPL19 (GenBank Accession No. NM_000981, RPL19 amplicon, SEQ ID No. 1630), TATA box (GenBank Accession No. NM_003194, TATA amplicon, SEQ ID No. 1633), UBC (GenBank Accession The expression of No. BC000449, Amplicon – Ubiquitin-Amplicon, SEQ ID NO: 328), and SDHA (GenBank Accession No. NM_004168, Amplicon – SDHA-Amplicon SEQ ID NO: 331) was similarly measured. For each RT sample, the expression of the amplicon was normalized to the geometric mean of the housekeeping gene dose. The normalized volume of each RT sample was divided by the median volume of lung samples (Sample Nos. 15-17 above, Table 3 above) to obtain the value of the relative expression of each sample relative to the median lung sample.

Forward primer (SEQ ID NO: 1691); CCGACGGCTCCTACTCCAA
Reverse primer (SEQ ID NO: 1692): GGAAGCTGTAGCCCATGGTGT
Reverse primer (SEQ ID NO: 1693): CCGACGGCTCCTACTCCATAAAAGCTGCTCATACCCGTGCCCGCCCAGGACGATGCGGGCATGTACATCTGCCTTGGCGCCAAACACCATGGGCTAAGCTTCTC

  The results are shown in FIG. 77, which shows the expression of Homo sapiens fibroblast growth factor receptor-like 1 (FGFRL1) H53626 transcripts detectable by the amplicon shown in the sequence name H53626seg25 in different normal tissues.

Expression of homo-Sapiens fibroblast growth factor receptor-like 1 (FGFRL1) H53626 transcripts detectable by the amplicon shown in the sequence name H53626junc24-27F1R3 in different normal tissues H53626junc24-27F1R3 amplicon (SEQ ID NO: 1690) as well as H53626junc24 The expression of homo-Sapiens fibroblast growth factor receptor-like 1 (FGFRL1) transcripts detectable by -27F1 (SEQ ID NO: 1688) and H53626 junc24-27R3 (SEQ ID NO: 1689) was measured by real time PCR. In parallel, four housekeeping genes-RPL19 (GenBank Accession No. NM_000981, RPL19 amplicon, SEQ ID No. 1630), TATA box (GenBank Accession No. NM_003194, TATA amplicon, SEQ ID No. 1633, primers SEQ ID No. 1631 and 1632 ), UBC (GenBank Accession No. BC000449, Amplicon – Ubiquitin-Amplicon, SEQ ID No. 328), and SDHA (GenBank Accession No. NM_004168, Amplicon – SDHA-Amplicon SEQ ID No. 331) Expression was measured as well. For each RT sample, the expression of the amplicon was normalized to the geometric mean of the housekeeping gene dose. The normalized volume of each RT sample was divided by the median volume of lung samples (Sample Nos. 15-17 above, Table 3 above) to obtain the value of the relative expression of each sample relative to the median lung sample.

Forward primer (SEQ ID NO: 1688): GTCCTTCCAGTGCAAGACCCA
Reverse primer (SEQ ID NO: 1689): TGGGCCTGGCAAAGCC
Reverse primer (SEQ ID NO: 1690): GTCCTTCCAGTGCAAGACCCAAAACCGCAAGGCCACCTGTGGCCTCCTCGTCCTCGGCCACTAGCCTGTCCGTGTGGCCGTGTGCATCGGCATCCCAGCCGGGCGCTGTCTTCATCGTGCTCCTGTCTGTCTGTCAGTCGGCCCA

  The results are shown in FIG. 78 and show the expression of homo-Sapiens fibroblast growth factor receptor-like 1 (FGFRL1) H53626 transcripts detectable by the amplicon shown in the sequence name H53626juncc24-27F1R3 in different normal tissues .

Expression of trophinin-related protein (Tastin) (T86235) transcript detectable by an amplicon as shown in SEQ ID NO: 1480 in normal and cancerous lung tissues Trophinin-related protein (Tastin) transcript detectable by SEQ ID NO: 1480 (eg The expression of variants nos. 23-26, 31, 32) represented by SEQ ID NOs: 1485-1488, 1609, 1610 was measured by real-time PCR. In parallel, four housekeeping genes-PBGD (GenBank Accession No. BC019323, Amplicon – SEQ ID No. 1471), HPRT1 (GenBank Accession No. NM_000194, Amplicon – SEQ ID No. 1468), Ubiquitin (Ubiquitin) The expression of GenBank Accession No. BC000449, Amplicon <#8211; SEQ ID No. 1474), and SDHA (GenBank Accession No. NM-004168, Amplicon >#8211; SEQ ID No: 1477) was similarly measured. For each RT sample, the expression of SEQ ID NO: 1480 was normalized to the geometric mean of the housekeeping gene dose. The normalized amount of each RT sample is the center of the amount of normal postmortem (PM) samples (sample numbers 47-50, 90-93, 96-99 above, Table 2, "tissue samples in the test panel") Divide by the value to obtain the magnification of the upregulation of each sample relative to the median of normal PM samples.

  FIG. 54a is a histogram showing over expression of the trophinin related protein (Tastin) transcript in cancerous lung tissue relative to a normal sample. The numbers and proportions of samples showing at least 5 times overexpression of the total number of samples tested are shown below.

  As evident from FIG. 54a, the expression of a trophinin related protein (Tastin) transcript detectable by SEQ ID NO: 1480 in a cancer sample is a non-cancerous sample (Sample Nos. 46-50, 90-93, 96-99, It was significantly higher than Table 2, "Tissue samples in test panel". Apparently, 6 out of 15 adenocarcinoma samples, 8 out of 16 squamous cell carcinoma samples, 2 out of 4 large cell carcinoma samples, 8 small cell carcinoma samples Overexpression of at least 5 fold was found in 8 of the

  Statistical analysis was applied to verify the significance of these results as described below.

  The P value for the difference in expression levels of trophinin-related protein (Tastin) transcripts detectable by SEQ ID NO: 1480 in lung cancer samples versus normal lung samples was determined to be 1.61 E-04 by T-test.

  The 5-fold overexpression threshold was found to be different between cancer and normal samples, and checked by Fisher's exact test, the P value was 1.49E-02. The above values indicate that the results are statistically significant.

  According to the invention, trophinin-related protein (Tastin) is a non-limiting example of a marker for diagnosing lung cancer. The trophinin-related protein (Tastin) markers of the present invention, alone or in combination, have various uses (including but not limited to lung cancer prognosis, prediction, screening, early screening, treatment selection, and treatment monitoring) It can be used for Although optionally any method can be used to detect over-expression and / or differential expression of this marker, preferably, NAT-based technology is used. Thus, optional and more preferably, any nucleic acid molecule capable of selectively hybridizing to a trophinin related protein (Tastin), as defined above, is also included in the present invention. Primer pairs are also optionally and preferably included within the scope of the present invention, for example, in the above experiments the following primers were used only as non-limiting examples of suitable primer pairs: Troffinin-related protein (Tastin)- TAA-seg44-forward primer (SEQ ID NO: 1478): AGACTCCAACCCACAGCCC trofinin-related protein (Tastin) -TAA-seg44-reverse primer (SEQ ID NO: 1479): CAGCTC AGCCAACCTTGCA.

  The present invention also preferably includes any amplicon obtained by use of any suitable primer pair (e.g. in the above experiments) and obtained the following amplicons only as a non-limiting illustration of a suitable amplicon : Troffinin related protein (Tastin) amplicon, SEQ ID NO: 1480: AGACTCCAACCCCACAGCCTGCGTGCACACAGTGAGCCTGATGGGAGGTGGGAACAGGGACAGGGGGCCACCTGGGCTGCTTCACAGAGGGTCAGCAGGAAGGCTTGGCTACAGTGCAAGGTTGGCTGAGCTTG.

  According to another preferred embodiment of the present invention, the trophinin-related protein (Tastin) or a fragment thereof comprises a biomarker for lung cancer detection. Optionally and more preferably, the trophinin-related protein (Tastin) splice variant or fragment thereof as set forth in SEQ ID NOs: 1485 to 1488, 1609, 1610 (eg, variants Nos. 23 to 26, 31, 32) Includes a marker. Optionally and more preferably, the fragment of trophinin related protein (Tastin) comprises the segment _TAA-44- SEQ ID NO: 1507. Similarly, optionally and more preferably, any suitable method can be used for detection of fragments such as, for example, trophinin related protein (Tastin) _segment_TAA-44- SEQ ID NO: 1507. Most preferably, NAT based technologies such as any nucleic acid molecule capable of specifically hybridizing with the fragment are used. Optionally and most preferably, primer pairs are used to obtain the fragments.

  According to yet another preferred embodiment, the present invention optionally and preferably comprises any amino acid sequence encoded by the nucleic acid sequence corresponding to the trophinin related protein (Tastin) described above or a fragment thereof (SEQ ID NO: 1492 1501, 1612 are included, but not limited to). Optionally, any oligopeptide or peptide for such amino acid sequence or fragment thereof (including but not limited to the unique amino acid sequences of these proteins as set forth in SEQ ID NOS: 1508-151, 1613) (Also or alternatively) can be used as a biomarker. The invention also optionally includes antibodies capable of recognizing and / or eliciting such oligopeptides or peptides.

  The invention also optionally and preferably comprises any nucleic acid sequence corresponding to the above-described trophinin related protein (Tastin) for any optional application or a fragment or amino acid sequence or a fragment thereof.

Expression of trophinin-related protein (Tastin) (T86235) transcript detectable by oligonucleotides as shown in SEQ ID NOs: 1512-1514 in normal and cancerous lung tissues Trophinin-related protein (Tastin) detectable by oligonucleotides SEQ ID NO: 1512-1514 ) (T86235) Transcripts (e.g. variants 8 to 10, 22, 23, 26, 27, 29 to 31, 33) as shown by SEQ ID NOs: 1481 to 1485, 1488 to 1491, 1609, 1611) Measured by oligonucleotide based microarray. The segments detected by the above-described oligonucleotides set forth in SEQ ID NOS: 1512-1514 are, for example, the nucleotide sequences set forth in SEQ ID NOS: 1503, 1504, 1506.

  The image intensity results for each feature were normalized according to the 90th percentile of the image intensity of all features on the chip. The feature image intensities of duplicates of the same nucleotide and duplicates of the same sample on the chip were then averaged. Discarded out of range results.

  For each oligonucleotide (SEQ ID NOs: 1512-1514), the averaged intensity determined for each sample is shown for all normal samples (Sample Nos. 48, 50, 90-92, 96-99 above, Table 2, "Test Divided by the averaged intensity of the tissue samples in the panel ") to obtain the upregulation magnification of each sample relative to the averaged normal sample. These data are shown in the histogram of FIG. 54b. As evident from FIG. 54 b, expression of trophinin-related protein (Tastin) (T86235) transcripts detectable using oligonucleotides of SEQ ID NOs: 1512-1514 in cancer samples was significantly higher than in normal samples .

  According to the invention, trophinin-related protein (Tastin) is a non-limiting example of a marker for diagnosing lung cancer. Although optionally any method can be used to detect over-expression and / or differential expression of this marker, preferably, NAT-based technology is used. Thus, optional and more preferably, any nucleic acid molecule capable of selectively hybridizing to a trophinin related protein (Tastin), as defined above, is also included in the present invention. Oligonucleotides are also optionally and preferably included within the scope of the present invention, for example, in the above experiments the following oligonucleotides were used as non-limiting examples of suitable oligonucleotides only: SEQ ID NOs: 1512-1514.

SEQ ID NO: 1512: CATGGTAACACGGCCTCCATGGCTGAGTAGGGGACTAGGAAGGGTAAAAG
SEQ ID NO: 1513: TGTACATCTAGGGCCTTCTAGTTAGGGGCTTCAATCCATTCCTCATGAGG
SEQ ID NO: 1514: TGTGAACACAAGAGGTCCTC ACCTC ACT GTGAGCTGCAACACCTGCCCTGC

  According to another preferred embodiment of the present invention, the trophinin-related protein (Tastin) or a fragment thereof comprises a biomarker for lung cancer detection. Optionally and more preferably, a trophinin-related protein as shown in SEQ ID NO: 1481-1485, 1488-1491, 1609, 1611 (for example, variant Nos. 8-10, 22, 23, 26, 27, 29-31, 33) (Tastin) The splice variant or fragment thereof comprises a biomarker for lung cancer detection. Optionally and more preferably, fragments of trophinin related protein (Tastin) comprise the segments TAA-14, 35, and 42-SEQ ID NO: 1503, 1504, 1506. Similarly, optionally and more preferably, any preferred method, for example for the detection of fragments such as trophinin related protein (Tastin) _segment_TAA-14, 35, and 42-SEQ ID NO: 1503, 1504, 1506, etc. It can be used for Most preferably, NAT based technologies such as any nucleic acid molecule capable of specifically hybridizing with the fragment are used. Optionally and most preferably, primer pairs are used to obtain the fragments.

  According to another preferred embodiment of the present invention, a trophinin-related protein (Tastin) splice variant comprising the unique segments as set forth in SEQ ID NOs: 1502 and 1505, such as those included in variants 9 and 29, respectively (SEQ ID NOs: 1482 and 1490) are useful as biomarkers for lung cancer detection.

  The invention also optionally and preferably comprises any nucleic acid sequence corresponding to the above-described trophinin related protein (Tastin) for any optional application or a fragment or amino acid sequence or a fragment thereof.

Expression of Homeobox C10 (HOXC10) (N31842) Transcript Detectable by the Amplicon Shown in SEQ ID NO: 1517 in Normal and Cancerous Lung Tissues Homeobox C10 (HOXC10) Transcript Detectable by SEQ ID NO: 1517 (eg The expression of variant No. 3) represented by SEQ ID No. 1519 was determined by real time PCR. In parallel, four housekeeping genes-PBGD (GenBank Accession No. BC019323, Amplicon – SEQ ID No. 1471), HPRT1 (GenBank Accession No. NM_000194, Amplicon – SEQ ID No. 3), Ubiquitin The expression of GenBank Accession No. BC000449, Amplicon <#8211; SEQ ID No. 9), and SDHA (GenBank Accession No. NM-004168, Amplicon >#8211; SEQ ID No: 1477) was similarly measured. For each RT sample, expression of SEQ ID NO: 1517 was normalized to the geometric mean of the housekeeping gene dose. The normalized amount of each RT sample is the center of the amount of normal postmortem (PM) samples (sample numbers 47-50, 90-93, 96-99 above, Table 2, "tissue samples in the test panel") Divide by the value to obtain the magnification of the upregulation of each sample relative to the median of normal PM samples.

  FIG. 55 is a histogram showing over expression of the homeobox C10 (HOXC10) transcript in cancerous lung tissue relative to a normal sample. The number and proportion of samples showing overexpression of at least 20 times of the total number of samples tested are shown below.

  As evident from FIG. 55, the expression of homeobox C10 (HOXC10) transcripts detectable by SEQ ID NO: 1517 in cancer samples is a non-cancerous sample (Sample Nos. 46-50, 90-93, 96-99, It was significantly higher than Table 2, "Tissue samples in test panel". Apparently, at least 20-fold overexpression in 6 out of 15 adenocarcinoma samples, 9 out of 16 squamous cell carcinoma samples, and 3 out of 4 large cell carcinoma samples Was found.

  Statistical analysis was applied to verify the significance of these results as described below.

  The P value for the difference in expression levels of homeobox C10 (HOXC10) transcripts detectable by SEQ ID NO: 1517 in lung cancer samples versus normal lung samples was determined to be 4.43E-03 by T-test.

  The 20-fold overexpression threshold was found to be different between cancer and normal samples, and checked by Fisher's exact test, the P value was 2.88E-02. The above values indicate that the results are statistically significant.

  According to the present invention, homeobox C10 (HOXC10) is a non-limiting example of a marker for diagnosing lung cancer. Homeobox C10 (HOXC10) markers according to the invention, alone or in combination, for various uses, including but not limited to lung cancer prognosis, prognosis, screening, early screening, treatment selection, and treatment monitoring It can be used for Although optionally any method can be used to detect over-expression and / or differential expression of this marker, preferably, NAT-based technology is used. Thus, optional and more preferably, any nucleic acid molecule capable of selectively hybridizing to homeobox C10 (HOXC10) as defined above is also included in the present invention. Primer pairs are also optionally and preferably included within the scope of the present invention, for example, in the above experiments the following primers were used as non-limiting illustrations of suitable primer pairs only.

Homeobox C10 (HOXC10)-Forward primer (SEQ ID NO: 1515): GCGAAACGCCGATTTGTTTGTT and Homeobox C10 (HOXC10)-Reverse primer (SEQ ID NO: 1516): CATCTGGAGGAGGGAGGGA

  The present invention also preferably includes any amplicon obtained by use of any suitable primer pair (e.g. in the above experiments) and obtained the following amplicons only as a non-limiting illustration of a suitable amplicon : Homeobox C10 (HOXC10) amplicon (SEQ ID NO: 1517).

GCGAAACGCGATTTGTTTGTTTGTGTGTGTGTGTGTGTGTGTGTGCGTGCGGGTGTGGGCTCCTGCGGCTTTGGCTGGGGCGGGGCTTGGGCAGCAGGACTGGAGCCGGAAGAGGTGGAGTGAAGGGCTGCCCAGCCTCCTCTCMTCGATC

  According to another preferred embodiment of the present invention, homeobox C10 (HOXC10) or a fragment thereof comprises a biomarker for lung cancer detection. Optionally and more preferably, the homeobox C10 (HOXC10) splice variant (eg, variant no. 3) as set forth in SEQ ID NO: 54 or a fragment thereof comprises a biomarker for lung cancer detection. Optionally and more preferably, the fragment of homeobox C10 (HOXC10) comprises the segment _TAA-seg6 (SEQ ID NO: 1526). Similarly, optionally and more preferably, any suitable method can be used for the detection of fragments such as, for example, homeobox C10 (HOXC10) _segment_TAA-seg6 (SEQ ID NO: 1526). Most preferably, NAT based technologies such as any nucleic acid molecule capable of specifically hybridizing with the fragment are used. Optionally and most preferably, primer pairs are used to obtain the fragments.

  According to another preferred embodiment of the present invention, a homeobox C10 (HOXC10) splice variant comprising the unique segments as set forth in SEQ ID NOS: 1524 and 1525 (eg, transcripts as set forth in SEQ ID NOS: 1515, 1519, and 1520) Contains a biomarker for lung cancer detection.

  According to yet another preferred embodiment, the present invention optionally and preferably comprises any amino acid sequence or fragment encoded by the nucleic acid sequence corresponding to the trophinin related protein (Tastin) described above (SEQ ID NOs: 1521 and 1522 (Including but not limited to). Optionally, any oligopeptide or peptide to such amino acid sequence or fragment thereof, including but not limited to, the unique amino acid sequence of the protein set forth in SEQ ID NO: 1523 (SEQ ID NO: 1522) It can be used as a biomarker (additionally or alternatively). The invention also optionally includes antibodies capable of recognizing and / or eliciting such oligopeptides or peptides.

  The invention also optionally and preferably comprises any nucleic acid sequence corresponding to the above-described trophinin related protein (Tastin) for any optional application or a fragment or amino acid sequence or a fragment thereof.

Expression of nucleoprotein 4 (NOL4)-(T06014) transcript detectable by an amplicon as shown in SEQ ID NO: 1529 in normal and cancerous lung tissue Nucleoprotein 4 (NOL4) transcript (eg, detectable by SEQ ID NO: 1529) , And the expression of mutant Nos. 3, 11 and 12) as shown by SEQ ID NOs: 1533, 1537, 1538, was measured by real-time PCR. In parallel, four housekeeping genes-PBGD (GenBank Accession No. BC019323, Amplicon – SEQ ID No. 1471), HPRT1 (GenBank Accession No. NM_000194, Amplicon – SEQ ID No. 1468), Ubiquitin (Ubiquitin) The expression of GenBank Accession No. BC000449, Amplicon <#8211; SEQ ID No. 1474), and SDHA (GenBank Accession No. NM-004168, Amplicon >#8211; SEQ ID No: 1477) was similarly measured. For each RT sample, expression of SEQ ID NO: 1529 was normalized to the geometric mean of the housekeeping gene dose. The normalized amount of each RT sample is the center of the amount of normal postmortem (PM) samples (sample numbers 47-50, 90-93, 96-99 above, Table 2, "tissue samples in the test panel") Divide by the value to obtain the magnification of the upregulation of each sample relative to the median of normal PM samples.

  FIGS. 56 a and b are histograms showing over expression of the nuclear protein 4 (NOL4) transcript in cancerous lung tissue relative to normal samples. The number and proportion of samples exhibiting at least 200-fold or 6-fold overexpression of the total number of samples tested are shown in FIGS. 56a and 56b below, respectively.

  As evident from FIG. 56a, expression of nucleoprotein 4 (NOL4) transcripts detectable by SEQ ID NO: 1529 in a sample from small cell lung cancer is a non-cancerous sample (samples 46-50, 90-93) , 96-99, Table 2, "Tissue Samples in Test Panels" were significantly higher. Clearly, at least 200-fold overexpression was observed in eight of the eight small cell carcinoma samples. As evident from FIG. 56b, at least 6-fold overexpression was found in 2 out of 15 adenocarcinoma samples and 3 out of 16 squamous cell carcinoma samples.

  Statistical analysis was applied to verify the significance of these results as described below.

  The P value for the difference in expression levels of nuclear protein 4 (NOL4) transcripts detectable by SEQ ID NO: 1529 in lung cancer samples versus normal lung samples was determined by T-test to be 1.36E-02.

  The 6-fold overexpression threshold was found to be different between cancer and normal samples, and checked by Fisher's exact test, the P value was 2.52E-02.

  The P value for the difference in expression levels of nuclear protein 4 (NOL4) transcripts detectable by SEQ ID NO: 1529 in small cell lung cancer samples versus normal lung samples was determined to be 3.86E-03 by T-test.

  The 200-fold overexpression threshold was found to be different between small cell carcinoma and normal lung samples, and checked by Fisher's exact test, the P value was 7.94E-06. The above values indicate that the results are statistically significant.

  According to the invention, nucleoprotein 4 (NOL4) is a non-limiting example of a marker for diagnosing lung cancer. The nuclear protein 4 (NOL4) markers of the present invention, alone or in combination, have a variety of uses, including, but not limited to, lung cancer prognosis, prognosis, screening, early screening, treatment selection, and treatment monitoring It can be used for Although optionally any method can be used to detect over-expression and / or differential expression of this marker, preferably, NAT-based technology is used. Thus, optional and more preferably, any nucleic acid molecule capable of selectively hybridizing to nucleoprotein 4 (NOL4), as defined above, is also included in the present invention. Primer pairs are also optionally and preferably included within the scope of the present invention, for example, in the above experiments the following primers were used as non-limiting illustrations of suitable primer pairs only.

Nucleoprotein 4 (NOL4)-TAA-seg 1-forward primer (SEQ ID NO: 1527): CTCGCTCCCTTTGCTCAACAC and nuclear protein 4 (NOL 4)-TAA-seg 1-reverse primer (SEQ ID NO: 1528): AAAGGGAAAGCGGGATGTTT

  The present invention also preferably includes any amplicon obtained by use of any suitable primer pair (e.g. in the above experiments) and obtained the following amplicons only as a non-limiting illustration of a suitable amplicon : Nuclear protein 4 (NOL4) amplicon (SEQ ID NO: 1529).

CTCGCTCCTGTTGCTCAACACACACGCACACACTCAGCACTCGGCGAGCAGGAGGCCACTGACCATTTTGCAAGTTCCAGGACCAGCTACAGCGCGGTGCGAAACATCCCGCTTCTCCTTT

  According to another preferred embodiment of the present invention, nucleoprotein 4 (NOL4) or a fragment thereof comprises a biomarker for lung cancer detection. Optionally and more preferably, the nucleoprotein 4 (NOL4) splice variant (eg, variants nos. 3, 11 and 12) set forth in SEQ ID NO: 1529 or fragments thereof comprise a biomarker for lung cancer detection. Optionally and more preferably, the fragment of nuclear protein 4 (NOL4) comprises the segment _TAA-seg-1 (SEQ ID NO: 1552). Similarly, optionally and more preferably, any suitable method may be used, for example, for the detection of fragments such as nucleoprotein 4 (NOL 4) _segment_TAA-seg-1 (SEQ ID NO: 1552) it can. Most preferably, NAT based technologies such as any nucleic acid molecule capable of specifically hybridizing with the fragment are used. Optionally and most preferably, primer pairs are used to obtain the fragments.

  According to another preferred embodiment of the present invention, a nucleoprotein 4 (NOL4) splice variant comprising the unique segment as set forth in SEQ ID NOS: 1554 and 1555 (eg, transcripts as set forth in SEQ ID NOS: 1534-1536 and 1539-1541) ) Includes biomarkers for lung cancer detection.

  According to yet another preferred embodiment, the present invention optionally and preferably comprises any amino acid sequence or fragment encoded by the nucleic acid sequence corresponding to the nucleoprotein 4 (NOL4) described above (SEQ ID NO: 1542, 1547) And 1543 and 1548, 1545, 1546, and 1549-1551 are included, but not limited to). Also, any oligopeptide or peptide for such amino acid sequence or fragment thereof (including but not limited to the unique amino acid sequence of the protein described in SEQ ID NO: 1544 (SEQ ID NO: 1543, 1546, 1549)) Optionally, it can be used as a biomarker (additionally or alternatively).

  The invention also optionally includes antibodies capable of recognizing and / or eliciting such oligopeptides or peptides.

  The invention also includes optional and preferably any nucleic acid sequence corresponding to nucleoprotein 4 (NOL4) described above for optional and optional application, or a fragment or amino acid sequence or fragment thereof.

Expression of nucleoprotein 4 (NOL 4)-(T06014) transcript detectable by an amplicon as shown in SEQ ID NO: 1532 in normal and cancerous lung tissue Nucleoprotein 4 (NOL 4) transcript (eg, detectable by SEQ ID NO: 1532) , And the expression of mutant Nos. 3, 11 and 12) as shown by SEQ ID NOs: 1533, 1537, 1538, was measured by real-time PCR. In parallel, four housekeeping genes-PBGD (GenBank Accession No. BC019323, Amplicon – SEQ ID No. 1471), HPRT1 (GenBank Accession No. NM_000194, Amplicon – SEQ ID No. 1468), Ubiquitin (Ubiquitin) The expression of GenBank Accession No. BC000449, Amplicon <#8211; SEQ ID No. 1474), and SDHA (GenBank Accession No. NM-004168, Amplicon >#8211; SEQ ID No. 1481) was similarly measured. For each RT sample, expression of SEQ ID NO: 1532 was normalized to the geometric mean of the housekeeping gene dose. The normalized amount of each RT sample is the center of the amount of normal postmortem (PM) samples (sample numbers 47-50, 90-93, 96-99 above, Table 2, "tissue samples in the test panel") Divide by the value to obtain the magnification of the upregulation of each sample relative to the median of normal PM samples.

  Figures 57a and b are histograms showing the overexpression of the nuclear protein 4 (NOL4) transcript in cancerous lung tissue relative to normal samples. The number and proportion of samples exhibiting at least 400-fold or 6-fold overexpression of the total number of samples tested are shown in FIGS. 57a and 56b below, respectively.

  As evident from FIG. 57a, expression of nucleoprotein 4 (NOL4) transcripts detectable by SEQ ID NO: 1532 in a sample from small cell lung cancer, non-cancerous samples (samples 46-50, 90-93) , 96-99, Table 2, "Tissue Samples in Test Panels" were significantly higher. Clearly, at least 400-fold overexpression was observed in eight of the eight small cell carcinoma samples. As apparent from FIG. 4 b, at least 6-fold overexpression was found in 4 out of 15 adenocarcinoma samples and 3 out of 16 squamous cell carcinoma samples.

  Statistical analysis was applied to verify the significance of these results as described below.

  The P value for the difference in expression levels of nuclear protein 4 (NOL4) transcripts detectable by SEQ ID NO: 1532 in lung cancer samples versus normal lung samples was determined to be 1.70E-02 by T-test.

  The 6-fold overexpression threshold was found to be different between cancer and normal samples, and checked by Fisher's exact test, the P value was 1.80E-02.

  The P value for the difference in expression levels of nuclear protein 4 (NOL4) transcripts detectable by SEQ ID NO: 1532 in small cell lung cancer samples versus normal lung samples was determined to be 7.08E-03 by T-test.

  The 400-fold overexpression threshold was found to differ between small cell carcinoma and normal lung samples, and checked by Fisher's exact test, the P value was 1.03E-04. The above values indicate that the results are statistically significant.

  According to the invention, nucleoprotein 4 (NOL4) is a non-limiting example of a marker for diagnosing lung cancer. The nuclear protein 4 (NOL4) markers of the present invention, alone or in combination, have a variety of uses, including, but not limited to, lung cancer prognosis, prognosis, screening, early screening, treatment selection, and treatment monitoring It can be used for Although optionally any method can be used to detect over-expression and / or differential expression of this marker, preferably, NAT-based technology is used. Thus, optional and more preferably, any nucleic acid molecule capable of selectively hybridizing to nucleoprotein 4 (NOL4), as defined above, is also included in the present invention. Primer pairs are also optionally and preferably included within the scope of the present invention, for example, in the above experiments the following primers were used as non-limiting illustrations of suitable primer pairs only.

Nuclear protein 4 (NOL4) – TAA-seg3-forward primer (SEQ ID NO: 1530): ACATCC CCCTGGAACGGAT and nuclear protein 4 (NOL 4)-TAA-seg3-reverse primer (SEQ ID NO: 1531): CAGAAATTAGCAAGACATTGATGG

  The present invention also preferably includes any amplicon obtained by use of any suitable primer pair (e.g. in the above experiments) and obtained the following amplicons only as a non-limiting illustration of a suitable amplicon : Nuclear protein 4 (NOL4) amplicon (SEQ ID NO: 1532).

ACATCC CCCTGGAACGGATATCTGTTTGGGGCACTACAATCTATCCTGTAGAACTAGTGCAAATCTCCATCAATGCTTTGCTAATTTCTG

  According to another preferred embodiment of the present invention, nucleoprotein 4 (NOL4) or a fragment thereof comprises a biomarker for lung cancer detection. Optionally and more preferably, the nucleoprotein 4 (NOL4) splice variant (e.g. variants nos. 3, 11, 12) as set forth in SEQ ID NOs: 1533, 1537, 1538 or fragments thereof comprise a biomarker for detecting lung cancer . Optionally and more preferably, the fragment of nuclear protein 4 (NOL4) comprises the segment _TAA-seg-3 (SEQ ID NO: 1553). Similarly, optionally and more preferably, any suitable method may be used, for example, for the detection of fragments such as nucleoprotein 4 (NOL 4) _segment_TAA-seg-3 (SEQ ID NO: 1553) it can. Most preferably, NAT based technologies such as any nucleic acid molecule capable of specifically hybridizing with the fragment are used. Optionally and most preferably, primer pairs are used to obtain the fragments.

  According to yet another preferred embodiment, the present invention optionally and preferably comprises any amino acid sequence or fragment encoded by the nucleic acid sequence corresponding to the nucleoprotein 4 (NOL4) described above (SEQ ID NO: 1542, 1547) , And 1548, but is not limited thereto). Any oligopeptide or peptide to such an amino acid sequence or a fragment thereof can optionally also be used as a biomarker (additionally or alternatively).

  The invention also optionally includes antibodies capable of recognizing and / or eliciting such oligopeptides or peptides.

  The invention also includes optional and preferably any nucleic acid sequence corresponding to nucleoprotein 4 (NOL4) described above for optional and optional application, or a fragment or amino acid sequence or fragment thereof.

Expression of the AA281370 Transcript Detectable by the Amplicon Shown in SEQ ID NO: 1558 in Normal and Cancerous Lung Tissues The AA281370 gene overexpressed in lung cancer was identified by the above calculation process. The AA281370-encoding protein (SEQ ID NO: 1563, 1564) contains several WD40 domains found in a number of eukaryotic proteins that cover a wide variety of functions (signal transduction, pre-mRNA processing, and cytoskeleton assembly Adapter molecules and / or regulatory molecules). As shown in FIG. 63, the WD43 domain region of the AA281370 encoding protein shown in SEQ ID NO: 1564 is somewhat similar, which may suggest involvement in the signal transduction MAPK pathway. For example, the region of the AA281370 polypeptide (SEQ ID NO: 1564) present between amino acids 40-790 is 75% homologous to the WD domain region of mouse Mapkbp1 protein (gi | 47124622) (FIG. 63a); The amino acids 40-886 of the peptide (SEQ ID NO: 1564) are 70% homologous to the rat JNK binding protein JNKBP1 (gi | 34856717) (FIG. 63 b).

  The expression of AA281370 transcripts detectable by SEQ ID NO: 1558 (e.g., variant nos. 0, 1, 4 and 5 as shown in SEQ ID NO: 1559-562) was measured by real time PCR. In parallel, four housekeeping genes-PBGD (GenBank Accession No. BC019323, Amplicon – SEQ ID No. 1471), HPRT1 (GenBank Accession No. NM_000194, Amplicon – SEQ ID No. 1468), Ubiquitin (Ubiquitin) The expression of GenBank Accession No. BC000449, Amplicon <#8211; SEQ ID No. 1474), and SDHA (GenBank Accession No. NM-004168, Amplicon > #8211; SEQ ID No: 1477) was similarly measured. For each RT sample, the expression of SEQ ID NO: 1558 was normalized to the geometric mean of the housekeeping gene dose. The normalized amount of each RT sample is the center of the amount of normal postmortem (PM) samples (sample numbers 47-50, 90-93, 96-99 above, Table 2, "tissue samples in the test panel") Divide by the value to obtain the magnification of the upregulation of each sample relative to the median of normal PM samples.

  FIG. 58 is a histogram showing over expression of the AA281370 transcript in cancerous lung tissue relative to normal samples. The number and proportion of samples showing at least 6-fold overexpression of the total number of samples tested is shown below.

  As evident from FIG. 58, expression of the AA281370 transcript detectable by SEQ ID NO: 1558 in a cancer sample was determined by the non-cancerous sample (Sample Nos. 46-50, 90-93, 96-99, Table 2, “Test Tissue samples in the panel ") were significantly higher. Apparently, at least 6-fold overexpression in 8 out of 8 small cell carcinoma samples, 2 out of 16 squamous cell carcinoma samples, 1 out of 4 large cell carcinoma samples Was found.

  Statistical analysis was applied to verify the significance of these results as described below.

  The P value for the difference in expression levels of AA281370 transcripts detectable by SEQ ID NO: 1558 in lung cancer samples versus normal lung samples was determined to be 8.58E-07 by T-test.

  The 6-fold overexpression threshold was found to be different between cancer and normal samples, and checked by Fisher's exact test, the P value was 4.81 E-02.

  The above values indicate that the results are statistically significant.

  According to the invention, the AA 281 370 transcript is a non-limiting example of a marker for diagnosing lung cancer. The use of the AA 281 370 markers of the invention, alone or in combination, for various uses, including, but not limited to, lung cancer prognosis, prognosis, screening, early screening, treatment selection, and treatment monitoring it can. Although optionally any method can be used to detect over-expression and / or differential expression of this marker, preferably, NAT-based technology is used. Thus, optional and more preferably, any nucleic acid molecule capable of selectively hybridizing to AA 281 370, as defined above, is also included in the present invention. Primer pairs are also optionally and preferably included within the scope of the present invention, for example, in the above experiments the following primers were used as non-limiting illustrations of suitable primer pairs only.

AA 281 370-Forward primer (SEQ ID NO: 1556): GGTTCGGATGGACTACACTTTGTC; and AA 281 370-Reverse primer (SEQ ID NO: 1557): CCACGTACTTCTGGGTGATGTC

  The present invention also preferably includes any amplicon obtained by use of any suitable primer pair (e.g. in the above experiments) and obtained the following amplicons only as a non-limiting illustration of a suitable amplicon : AA 281 370 amplicon (SEQ ID NO: 1558).

AA 281 370-Amplicon (SEQ ID NO: 1558): GGTTCGGATGGACTACACTTTTGTCCGTACCCACCACGTAGCAGAGAAAACCACCTTTGATGACATGGACATTGACATCACCCAGAAGTACGTGG

  According to another preferred embodiment of the present invention, AA281370 or a fragment thereof comprises a biomarker for lung cancer detection. Optionally and more preferably, the AA281370 splice variant (eg, variants nos. 0, 1, 4 and 5) set forth in SEQ ID NO: 1558 or fragments thereof comprise a biomarker for lung cancer detection. Optionally and more preferably, the fragment of AA281370 comprises the segment _TAA-seg10 (SEQ ID NO: 1567). Similarly, optionally and more preferably, any suitable method can be used for detection of fragments such as, for example, AA281370_segment_TAA-seg10 (SEQ ID NO: 1567). Most preferably, NAT based technologies such as any nucleic acid molecule capable of specifically hybridizing with the fragment are used. Optionally and most preferably, primer pairs are used to obtain the fragments.

  According to another preferred embodiment, the present invention also optionally and more preferably an AA 281 370 splice variant comprising a unique segment as set forth in SEQ ID NO: 1568 (eg, transcripts as set forth in SEQ ID NOs: 1561 and 1562) Contains a biomarker for lung cancer detection.

  According to yet another preferred embodiment, the present invention optionally and preferably comprises any amino acid sequence or fragment encoded by the nucleic acid sequence corresponding to AA 281 370 described above (SEQ ID NOs: 1563-1566, Not limited thereto). Any oligopeptide or peptide for such amino acid sequence or fragment thereof (including but not limited to the unique amino acid sequence of the proteins set forth in SEQ ID NOS: 1569, 1570, and 1571 (SEQ ID NOS: 1563-1566)) Also, optionally, it can be used as a biomarker (also or alternatively).

  The invention also optionally includes antibodies capable of recognizing and / or eliciting such oligopeptides or peptides.

  The present invention also includes optional and preferably any nucleic acid sequence corresponding to AA 281 370 described above for optional optional applications or fragments or amino acid sequences or fragments thereof.

Expression of Sulfatase 1 (SULF1)-(Z21 368) Transcript Detectable by the Amplicon Shown in SEQ ID NO: 1574 in Normal and Cancerous Lung Tissues SULF 1 is a secreted protein found in extracellular matrix. SULF1 is known to be downregulated in many epithelial cancer types.

  The expression of sulfatase 1 (SULF1) transcripts detectable by SEQ ID NO: 1574 (eg SEQ ID NO: 1578, variant nos. 13 and 14 shown in 1579) was measured by real time PCR. In parallel, four housekeeping genes-PBGD (GenBank Accession No. BC019323, Amplicon – SEQ ID No. 1471), HPRT1 (GenBank Accession No. NM_000194, Amplicon – SEQ ID No. 1468), Ubiquitin (Ubiquitin) The expression of GenBank Accession No. BC000449, Amplicon <#8211; SEQ ID No. 1474), and SDHA (GenBank Accession No. NM-004168, Amplicon > #8211; SEQ ID No: 1477) was similarly measured. For each RT sample, expression of SEQ ID NO: 1574 was normalized to the geometric mean of the housekeeping gene dose. The normalized amount of each RT sample is the center of the amount of normal postmortem (PM) samples (sample numbers 47-50, 90-93, 96-99 above, Table 2, "tissue samples in the test panel") Divide by the value to obtain the magnification of the upregulation of each sample relative to the median of normal PM samples.

  FIG. 59 is a histogram showing over expression of the above-mentioned sulfatase 1 (SULF1) transcript in cancerous lung tissue relative to a normal sample. The number and proportion of samples showing at least 8 times overexpression of the total number of samples tested is shown below.

  As evident from FIG. 59, the expression of sulfatase 1 (SULF1) transcript detectable by SEQ ID NO: 1574 in cancer samples from non-cellular cancer is a non-cancerous sample (Sample Nos. 46-50, 90-93, 96-99, Table 2, "Tissue samples in test panel" were significantly higher. Apparently, at least 8-fold overexpression is observed in 11 out of 15 adenocarcinoma samples, 11 out of 16 squamous cell carcinoma samples, 4 out of 4 large cell carcinoma samples It was found.

  Statistical analysis was applied to verify the significance of these results as described below.

  The P value for the difference in expression levels of sulfatase 1 (SULF1) transcripts detectable by SEQ ID NO: 1574 in lung cancer samples versus normal lung samples was determined to be 3.18E-07 by T-test.

  The 8-fold overexpression threshold was found to differ between cancer and normal samples, and checked by Fisher's exact test, the P value was 1.18E-04.

  The above values indicate that the results are statistically significant.

  According to the invention, sulfatase 1 (SULF1) is a non-limiting example of a marker for diagnosing lung cancer. The sulfatase 1 (SULF1) markers of the present invention, alone or in combination, have a variety of uses, including but not limited to lung cancer prognosis, prognosis, screening, early screening, treatment selection, and treatment monitoring. It can be used. Although optionally any method can be used to detect over-expression and / or differential expression of this marker, preferably, NAT-based technology is used. Thus, optional and more preferably, any nucleic acid molecule capable of selectively hybridizing to sulfatase 1 (SULF1), as defined above, is also included in the present invention. Primer pairs are also optionally and preferably included within the scope of the present invention, for example, in the above experiments the following primers were used as non-limiting illustrations of suitable primer pairs only.

  Sulfatase 1 (SULF1)-Forward primer (SEQ ID NO: 1572): ACTCACTCAGAGACTACACACAAGGAAG and sulfatase 1 (SULF1)-reverse primer (SEQ ID NO: 1573): AGTATGGGAAGAATT TACTTGTCCAA

  The present invention also preferably includes any amplicon obtained by use of any suitable primer pair (e.g. in the above experiments) and obtained the following amplicons only as a non-limiting illustration of a suitable amplicon : Sulfatase 1 (SULF1) amplicon (SEQ ID NO: 1574).

  ACTCACTCAGAGACTAACAACAAAGGA AGTAATTTCTTACCTGGTCATTATTTAGTCTACAATAAGTTCATCCTTCTTCAGTGTGACCAGTAAATTCTTCCCATACT

  According to another preferred embodiment of the present invention, sulfatase 1 (SULF1) or a fragment thereof comprises a biomarker for lung cancer detection. Optionally and more preferably, the sulfatase 1 (SULF1) splice variant (eg, variants nos. 13 and 14) as set forth in SEQ ID NO: 1578, 1579 or fragments thereof comprise a biomarker for lung cancer detection. Optionally and more preferably, the fragment of sulfatase 1 (SULF1) comprises the segment _TAA-seg5 (SEQ ID NO: 1587). Similarly, optionally and more preferably, any suitable method can be used for detection of fragments such as, for example, sulfatase 1 (SULF1) _segment_TAA-seg5 (SEQ ID NO: 1857). Most preferably, NAT based technologies such as any nucleic acid molecule capable of specifically hybridizing with the fragment are used. Optionally and most preferably, primer pairs are used to obtain the fragments.

  According to another preferred embodiment of the present invention, a sulfatase 1 (SULF1) splice variant comprising the unique segment according to SEQ ID NO: 1588, 1591 (e.g. the transcript according to SEQ ID NO: 1575 to 1577) detects lung cancer For the use of biomarkers.

  According to yet another preferred embodiment, the present invention optionally and preferably comprises any amino acid sequence or fragment encoded by the nucleic acid sequence corresponding to the above-mentioned sulfatase 1 (SULF1) (SEQ ID NO: 1586, 1580, 1582 (including but not limited to 1584). These include the unique amino acid sequences of any of the oligopeptides or peptides for such amino acid sequences or fragments thereof (SEQ ID NOS: 1581, 1583 and 1585 respectively (SEQ ID NOs: 1580, 1582 and 1584) respectively Can also be optionally used (or additionally) as a biomarker.

  The invention also optionally includes antibodies capable of recognizing and / or eliciting such oligopeptides or peptides.

  The invention also includes optional and preferably any nucleic acid sequence corresponding to nucleoprotein 4 (NOL4) described above for optional and optional application, or a fragment or amino acid sequence or fragment thereof.

Expression of SRY (Gesity Determining Area Y)-Box 2 (SOX 2)-(HUMHMGBOX) Transcript Detectable by the Amplicon Shown in SEQ ID NO: 1594 in Normal and Cancerous Lung Tissues SOX 2 Transcription Detectable by SEQ ID NO: 1594 Expression of the product (eg, variant No. 0 as shown by SEQ ID NO: 1595) was measured by real-time PCR. In parallel, four housekeeping genes-PBGD (GenBank Accession No. BC019323, Amplicon – SEQ ID No. 1471), HPRT1 (GenBank Accession No. NM_000194, Amplicon – SEQ ID No. 1468), Ubiquitin (Ubiquitin) The expression of GenBank Accession No. BC000449, Amplicon <#8211; SEQ ID No. 1474), and SDHA (GenBank Accession No. NM-004168, Amplicon >#8211; SEQ ID No: 1477) was similarly measured. For each RT sample, expression of SEQ ID NO: 1594 was normalized to the geometric mean of housekeeping gene amounts. The normalized amount of each RT sample is the center of the amount of normal postmortem (PM) samples (sample numbers 47-50, 90-93, 96-99 above, Table 2, "tissue samples in the test panel") Divide by the value to obtain the magnification of the upregulation of each sample relative to the median of normal PM samples.

  FIG. 60 is a histogram showing overexpression of the SOX2 transcript in cancerous lung tissue relative to normal samples. The number and proportion of samples showing at least 5 times overexpression of the total number of samples tested is shown below.

  As apparent from FIG. 60, the expression of SOX2 transcripts detectable by SEQ ID NO: 1594 in lung cancer-derived cancer samples was observed in non-cancerous samples (sample Nos. 46-50, 90-93, 96-99, Table 2). , "Tissue samples in the test panel" was significantly higher. Evidently, 4 out of 15 adenocarcinoma samples, 10 out of 16 squamous cell carcinoma samples, 2 out of 4 large cell carcinoma samples, and 8 small cell carcinomas Overexpression of at least 5 fold was found in 7 of the

  Statistical analysis was applied to verify the significance of these results as described below.

  The P value for the difference in expression levels of SOX2 transcripts detectable by SEQ ID NO: 1594 in lung cancer samples versus normal lung samples was determined to be 4.38E-05 by T-test.

  The 5-fold overexpression threshold was found to be different between cancer and normal samples, and checked by Fisher's exact test, the P value was 8.09E-04.

  The above values indicate that the results are statistically significant.

  According to the present invention, SOX2 is a non-limiting example of a marker for diagnosing lung cancer. The use of the SOX2 markers of the invention, alone or in combination, for various uses, including but not limited to lung cancer prognosis, prognosis, screening, early screening, treatment selection, and treatment monitoring it can. Although optionally any method can be used to detect over-expression and / or differential expression of this marker, preferably, NAT-based technology is used. Thus, optional and more preferably, any nucleic acid molecule capable of selectively hybridizing to SOX2 as defined above is also included in the present invention. Primer pairs are also optionally and preferably included within the scope of the present invention, for example, in the above experiments the following primers were used as non-limiting illustrations of suitable primer pairs only.

SOX 2-forward primer (SEQ ID NO: 1592): GGCGGCGGCAGGAT and SOX 2-reverse primer (SEQ ID NO: 1593): GTCGGGAGCGCAGGG

  The present invention also preferably includes any amplicon obtained by use of any suitable primer pair (e.g. in the above experiments) and obtained the following amplicons only as a non-limiting illustration of a suitable amplicon : SOX2 amplicon (SEQ ID NO: 1594).

  GGCGGCGGCAGGATCGGCCAGAGGAGAGGAGGGAAGCGCTTTTTTTGATCCTGATTCCAGTTTGCCTCTCTCTTTTTTTCCCCCAA AATTATTCTTCGCCTGAATTTTCTCTGCGGCAGCCCTGCGCTCCGACAC

  According to another preferred embodiment of the invention, SOX2 or a fragment thereof comprises a biomarker for lung cancer detection. Optionally and more preferably, the SOX2 splice variant (eg, variant No. 0) as set forth in SEQ ID NO: 1595 or a fragment thereof comprises a biomarker for lung cancer detection. Optionally and more preferably, the fragment of SOX2 comprises the segment _TAA-seg2 (SEQ ID NO: 1597). Similarly, optionally and more preferably, any suitable method can be used for detection of fragments such as, for example, SOX2_segment_TAA-seg2 (SEQ ID NO: 1597). Most preferably, NAT based technologies such as any nucleic acid molecule capable of specifically hybridizing with the fragment are used. Optionally and most preferably, primer pairs are used to obtain the fragments.

  According to yet another preferred embodiment, the present invention optionally and preferably comprises any amino acid sequence or fragment encoded by a nucleic acid sequence corresponding to SOX2 as described above (including SEQ ID NO: 1596) Not limited). Any oligopeptide or peptide to such an amino acid sequence or a fragment thereof can optionally also be used as a biomarker (additionally or alternatively).

  The invention also optionally includes antibodies capable of recognizing and / or eliciting such oligopeptides or peptides.

  The invention also optionally and preferably comprises any nucleic acid sequence corresponding to SOX above for any optional application or a fragment thereof or an amino acid sequence or a fragment thereof.

Expression of detectable placophilin 1 (ectoderm dysplasia / epidermal blister syndrome) (PKP1)-(HSB6PR) transcript detectable by the amplicon shown in SEQ ID NO: 1600 in normal and cancerous lung tissue: detectable by SEQ ID NO: 1600 The expression of PKP1 transcripts (e.g., variant nos. 0, 5, and 6 as shown by SEQ ID NOs: 1601-1603) was measured by real time PCR. In parallel, four housekeeping genes-PBGD (GenBank Accession No. BC019323, Amplicon – SEQ ID No. 1471), HPRT1 (GenBank Accession No. NM_000194, Amplicon – SEQ ID No. 1468), Ubiquitin (Ubiquitin) The expression of GenBank Accession No. BC000449, Amplicon <#8211; SEQ ID No. 1474), and SDHA (GenBank Accession No. NM-004168, Amplicon >#8211; SEQ ID No: 1477) was similarly measured. For each RT sample, the expression of SEQ ID NO: 1600 was normalized to the geometric mean of the housekeeping gene dose. The normalized amount of each RT sample is the center of the amount of normal postmortem (PM) samples (sample numbers 47-50, 90-93, 96-99 above, Table 2, "tissue samples in the test panel") Divide by the value to obtain the magnification of the upregulation of each sample relative to the median of normal PM samples.

  FIG. 61 is a histogram showing over expression of the above PKP1 transcripts in cancerous lung tissue relative to normal samples. The number and proportion of samples showing at least 7-fold overexpression of the total number of samples tested are shown below.

  As apparent from FIG. 61, the expression of PKP1 transcript detectable by SEQ ID NO: 1600 in a lung cancer-derived cancer sample was detected in non-cancerous samples (Sample Nos. 46-50, 90-93, 96-99, Table 2 , "Tissue samples in the test panel" was significantly higher. Apparently, at least 7-fold overexpression was found in 1 of 11 out of 16 squamous cell carcinoma samples and in 1 of 4 large cell carcinoma samples.

  Statistical analysis was applied to verify the significance of these results as described below.

  The P value for the difference in expression levels of PKP1 transcripts detectable by SEQ ID NO: 1600 in lung cancer samples versus normal lung samples was determined to be 3.18E-03 by T-test.

  The 7-fold overexpression threshold was found to be different between cancer and normal samples, and checked by Fisher's exact test, the P value was 3.50E-02.

  The above values indicate that the results are statistically significant.

  According to the invention, PKP1 is a non-limiting example of a marker for diagnosing lung cancer. The use of the PKP1 markers of the invention, alone or in combination, for various uses including, but not limited to, lung cancer prognosis, prognosis, screening, early screening, treatment selection, and treatment monitoring it can. Although optionally any method can be used to detect over-expression and / or differential expression of this marker, preferably, NAT-based technology is used. Thus, optional and more preferably, any nucleic acid molecule capable of selectively hybridizing to PKP1, as defined above, is also included in the present invention. Primer pairs are also optionally and preferably included within the scope of the present invention, for example, in the above experiments the following primers were used as non-limiting illustrations of suitable primer pairs only.

PKP1-forward primer (SEQ ID NO: 1598): CCCCAGACTCTGTGCACTTCA and PKP1-reverse primer (SEQ ID NO: 1599): TGGGCTCTGCTCTGTCTTAGTGTA

  The present invention also preferably includes any amplicon obtained by use of any suitable primer pair (e.g. in the above experiments) and obtained the following amplicons only as a non-limiting illustration of a suitable amplicon : PKP1 amplicon (SEQ ID NO: 1600).

Amplicon (SEQ ID NO: 1600): CCCCAGACTCTGTGCACTTCAGACCAGCAGCAGCAGGAGGGCTCCCGAGGGCCTTATGAGAAAACCTGTGTGGACATCC CTTGGTGTACACTAAGACAGAGCAGAGCCCCA

  According to another preferred embodiment of the present invention, PKP1 or a fragment thereof comprises a biomarker for lung cancer detection. Optionally and more preferably, the PKP1 splice variants (eg, variants nos. 0, 5, and 6) set forth in SEQ ID NOS: 1601-1603 or fragments thereof comprise a biomarker for lung cancer detection. Optionally and more preferably, the fragment of PKP1 comprises the segment _TAA-seg34 (SEQ ID NO: 1608). Similarly, optional and more preferably, any suitable method can be used for detection of fragments such as, for example, PKP1_segment_TAA-seg34 (SEQ ID NO: 1608). Most preferably, NAT based technologies such as any nucleic acid molecule capable of specifically hybridizing with the fragment are used. Optionally and most preferably, primer pairs are used to obtain the fragments.

  According to another preferred embodiment of the present invention, a PKP1 splice variant (for example, variant 6 according to SEQ ID NO: 1603) comprising the unique segment according to SEQ ID NO: 1607 is suitable as a biomarker for lung cancer detection .

  According to yet another preferred embodiment, the present invention optionally and preferably comprises any amino acid sequence or fragment encoded by a nucleic acid sequence corresponding to PKP1 as described above (SEQ ID NOS: 1604-1606, Not limited thereto). Any oligopeptide or peptide to such an amino acid sequence or a fragment thereof can optionally also be used as a biomarker (additionally or alternatively).

  The invention also optionally includes antibodies capable of recognizing and / or eliciting such oligopeptides or peptides.

  The invention also optionally and preferably comprises any nucleic acid sequence corresponding to PKP1 described above for any optional application or a fragment or amino acid sequence or a fragment thereof.

Combined expression of 12 sequences (SEQ ID NO: 1480, 1517, 1529, 1532, 1558, 1574, 1594, 1600, 1616, 1619, 1622, 1625) in normal and cancerous lung tissue SEQ ID NO: 1480, 1517, 1529, 1532, The expression of several transcripts detectable by 1558, 1574, 1594, 1600, 1616, 1619, 1622, 1625 was measured by real-time PCR (expression of each SEQ ID NO was checked separately). In parallel, four housekeeping genes-PBGD (GenBank Accession No. BC019323, Amplicon – SEQ ID No. 1471), HPRT1 (GenBank Accession No. NM_000194, Amplicon – SEQ ID No. 1468), Ubiquitin (Ubiquitin) The expression of GenBank Accession No. BC000449, Amplicon <#8211; SEQ ID No. 1474), and SDHA (GenBank Accession No. NM-004168, Amplicon >#8211; SEQ ID No: 1477) was similarly measured. For each RT sample, the expression of SEQ ID NOs: 1480, 1517, 1529, 1532, 1558, 1574, 1594, 1600, 1616, 1619, 1622, 1625 was normalized to the geometric mean of the housekeeping gene dose. The normalized amount of each RT sample is the center of the amount of normal postmortem (PM) samples (sample numbers 47-50, 90-93, 96-99 above, Table 2, "tissue samples in the test panel") Divide by the value to obtain the magnification of the upregulation of each sample relative to the median of normal PM samples.

  Figure 62 is a histogram showing over expression of the above transcripts in cancerous lung tissue relative to normal samples. The number and ratio of samples showing at least 10-fold overexpression in at least one of the above SEQ ID NOs among the total number of samples tested is shown below.

  As apparent from FIG. 62, in at least one of the above SEQ ID NOs, 15, 15 out of 15 adenocarcinoma samples, 15 out of 16 squamous cell carcinoma samples, 4 large cell carcinoma samples At least 10-fold overexpression was found in 4 of 8 and 8 of 8 small cell carcinoma samples.

  Statistical analysis was applied to verify the significance of these results as described below. The threshold of at least one 10-fold overexpression of the amplicon according to SEQ ID NOs: 1480, 1517, 1529, 1532, 1558, 1574, 1594, 1600, 1616, 1619, 1622, 1625 is between cancer and normal samples It was found to be different and checked by Fisher's exact test, the P value was 2.37E-08.

  The above values indicate that the results are statistically significant.

Kits and Diagnostic Assays and Methods The markers described with respect to any of the above examples alone, other markers as described above and / or other completely different markers (UbcH10 (2004 respectively 1 U.S. Patent Application Nos. 60 / 535,904 and 60 / 572,122 filed on May 13 and March 19 (see Attorney Docket Nos. 27080 and 28045), Troponin (US Patent Application No. 60) / 539, 129 (see Attorney Docket No. 26940), Sim 2 (see PCT Application No. WO 2004/012847), PE-10 (SP-A), TTF-1, Cytokeratin 5/6 Can be used in combination with, but not limited to. The application is incorporated herein by reference as if fully described herein, and these markers are combined with other markers for a number of uses (prognosis, prognosis of lung cancer, It can be used for screening, early screening, selection of treatment, and monitoring of treatment, including but not limited to (and optionally, also staging of disease). These allow the diagnostician to obtain more information compared to the results obtained using only one marker, increasing the proportion of true positive and true negative diagnoses, false positives Or the rate of false negative diagnoses decreases.

  Assays and methods of the invention include, but are not limited to, immunoassays, hybridization assays, and NAT-based assays, as described above. Combinations of the markers of the invention with the other markers described above and / or completely different markers to aid in lung cancer diagnosis can be performed as a combination of NAT-based assays, immunoassays, and hybridization assays. . According to a preferred embodiment of the invention, the assay is a NAT based assay as described by way of example for the above example.

  In still another aspect, the present invention provides a kit for assisting lung cancer diagnosis, which kit can be used to detect the marker of the present invention. For example, the kit can be used to detect any one or a combination of the above markers differentially present in lung cancer and normal patient samples. The kits of the invention have broad application. For example, using the kit to identify whether a subject has small cell lung cancer, non-small cell lung cancer, adenocarcinoma, bronchoalveolar carcinoma, squamous cell carcinoma, or large cell carcinoma, or to make a negative diagnosis Can help diagnose lung cancer. In another example, the kit can be used to identify compounds that modulate marker expression in in vitro lung cells for lung cancer or in vivo animal models.

In one embodiment, the kit comprises (a) a substrate comprising an adsorbent, wherein the adsorbent is suitable for binding a marker, and (b) a wash or instructions for the preparation of a wash. The aforementioned marker is detected by the combination of the adsorbent and the washing solution.

  Optionally, the kit may further comprise an explainer for appropriate operating parameters in the form of a label or another insert. For example, the kit may have standard instructions that provide the consumer / kit user with information on how to wash the probe after seminal plasma samples or other tissue samples contact the probe. .

  In another embodiment, the kit comprises (a) an antibody that specifically binds to the marker and (b) a detection reagent. Such kits can be prepared from the materials described above.

  In any of the embodiments, the kit optionally compares the test sample to a control information standard and / or a control amount such that the test amount of the marker detected in the sample is at a diagnostic amount consistent with a lung cancer diagnosis. It may further include standard or control information and / or control amounts of material such that it can be determined whether there is any.

Therapeutic Applications of the Splice Variants of the Invention The splice variants described herein (including any polynucleotides, oligonucleotides, polypeptides, peptides, or fragments thereof) or antibodies that specifically bind to these Can optionally be used, for example, in therapeutic applications to treat the diseases described herein with respect to its diagnostic application. A "mutant treatable" disease refers to any disease treatable by use of a splice variant of any of the therapeutic proteins of the invention. "Treatment" also includes prevention, amelioration, elimination, and control of the disease and / or pathological condition. Diseases where such variants may be useful therapeutic agents are described in more detail below for each variant. As these variants are splice variants of known proteins, the variants themselves are described as "clusters" or genes. Thus, "cluster related disease" or "mutant related disease" refers to a disease that can be treated with a particular protein (the therapeutic protein variant of the present invention with respect to the description of such diseases).

  As used herein, the term "biologically active" refers to a protein having the structure, regulation, or biochemical function of a naturally occurring molecule. Similarly, "immunologically active" means that a natural, recombinant, or synthetic ligand or any of these oligopeptides induce a specific immune response in a suitable animal or cell to bind to a specific antibody. I say ability.

  As used herein, the term "modulate" refers to a change in the activity of at least one receptor mediated activity. For example, modulation can increase or decrease the activity of the protein, the binding properties, or any other biological, functional or immunological properties of the ligand.

Methods of Treatment As noted above, the novel therapeutic protein variants of the invention and compositions derived therefrom (ie, peptides, oligonucleotides) can be used to treat cluster related diseases.

  Thus, according to a further aspect of the present invention there is provided a method of treating a cluster related disease in a subject.

  The subject of the invention is a mammal, preferably a human, having at least one type of cluster related disease as described above.

  As noted above, the sequences of the biomolecules of the invention can be used to treat a subject having the disease.

  The subject of the present invention is a mammal, preferably a human, diagnosed as suffering from one of the above mentioned diseases or susceptible to one of the above mentioned diseases.

  As used herein, the term "treatment" refers to curing, reversing, alleviating, alleviating, alleviating, minimizing, suppressing or preventing side effects of the disease.

  According to the invention, treatment can be by specific upregulation or downregulation of the expression of at least one polypeptide of the invention in a subject.

  Optionally, it can be upregulated by administration to a subject of at least one of the polypeptides of the invention described herein (eg, recombinant or synthetic) or an active portion thereof. However, since the bioavailability of large polypeptides is potentially relatively small due to the high degree of degradation and low permeability, administration of the polypeptide may be a small peptide fragment (eg, about 100 amino acids) It is preferable to restrict to The polypeptide or peptide can optionally be administered in a pharmaceutical composition as described in more detail below.

  It is recognized that the treatment of the above diseases of the present invention can be combined with other treatment methods known in the art (ie combination therapy). Thus, treatment of malignancies using the agents of the invention can be combined, for example, with radiation therapy, antibody therapy, and / or chemotherapy.

  Alternatively or additionally, the upregulation method can optionally be performed by specific upregulation in a subject of an amount (optionally expression) of at least one of the polypeptides of the invention or an active part thereof.

  The biomolecular sequences of this aspect of the invention, as described above and in the examples below, are used to treat diseases in which changes in activity or expression of the wild type gene product are known to contribute to the onset or progression of the disease Can be used as a valuable therapeutic tool for For example, if the disease is due to overexpression of a membrane bound receptor, the soluble variant can be used as an antagonist that competes with the receptor for binding thereby terminating signaling from the receptor.

  Examples of such diseases are listed in the Examples section below.

  It will be appreciated that the polypeptides of the invention may also have agonistic properties. These include the stability of the ligand (eg, IL-4), protection from proteolysis, and modification of the pharmacokinetic properties of the ligand (ie, the half life of the ligand is increased while its clearance is decreased Is included. Thus, the biomolecular sequences of this aspect of the invention can be used to treat conditions or diseases in which the wild-type gene product plays a favorable role (e.g. increased angiogenesis in diabetes or ischemia).

  The exogenous protein of the present invention wherein the therapeutic protein variant expression of the present invention is ligated to a nucleic acid expression construct designed for expression of the coding sequence in eukaryotic cells (eg mammalian cells) as described above It can be upregulated via the administration of at least one of the polynucleotide sequences. Thus, the exogenous polynucleotide sequence may be DNA or RNA encoding a variant of the invention or an active portion thereof.

  It will be appreciated that the nucleic acid construct can be administered to an individual using any suitable mode of administration described below (ie, in-vivo gene therapy). Alternatively, the nucleic acid construct is introduced into an appropriate cell by an appropriate gene delivery body / method (transfection, transduction, homologous recombination, etc.) and an expression system as needed, and the modified cell is expanded in culture, and the individual (Ie, ex-vivo gene therapy). Nucleic acid constructs are described in more detail above.

  It will be appreciated that the method can also be performed by specific endogenous upregulation of the expression of the variant of the invention in a subject. Agents for upregulation of the endogenous expression of specific splice variants of a given gene include antisense oligonucleotides directed to the splice site of interest, thereby altering the splicing pattern of the gene. This approach is described in Bcl-x (Taylor (1999) Nat. Biotechnol. 17: 1097-1100; and Mercatante (2001) J. Biol. Chem. 276: 16411-16417), IL-5R (Karras (2000) Mol. Pharmacol. 58: 380-387) and c-myc (Giles (1999) Antisense Acid Drug Dev. 9: 213-220) have been successfully used to alter the balance of expression of the two isoforms.

  For example, interleukin 5 and its receptor play an important role as regulators of hematopoiesis and as mediators in several inflammatory diseases such as allergy and asthma. Two alternatively spliced isoforms are generated from the IL-5R gene and each contain exon 9 (i.e. long form) and are excluded (i.e. short form). The long form encodes an intact membrane bound receptor, and the shorter form encodes a secreted soluble nonfunctional receptor. Using 2'-O-MOE-oligonucleotides specific for the exon 9 region, Karas and co-workers (above) significantly reduce wild type receptor expression and express shorter isoforms It could be increased. The design and synthesis of oligonucleotides that can be used in the present invention are described below, according to Sazani and Kole (2003) Progress in Molecular and Subcellular Biology 31: 217-239.

  An exogenous polynucleotide sequence of the invention (eg, SEQ ID NO: 3, 7, 11, 15, 19) ligated to a nucleic acid expression construct designed for expression of a coding sequence in a eukaryotic cell (eg, a mammalian cell). , 23, 27, 31, 35, 39 or 43) can upregulate the expression of a polypeptide of the invention in a subject. Thus, the exogenous polynucleotide sequence may be a DNA or RNA sequence encoding a variant of the invention or an active portion thereof.

  It will be appreciated that the nucleic acid construct can be administered to an individual using any suitable mode of administration described below (ie, in-vivo gene therapy). Alternatively, the nucleic acid construct is introduced into an appropriate cell by an appropriate gene delivery body / method (transfection, transduction, homologous recombination, etc.) and an expression system as needed, and the modified cell is expanded in culture, and the individual (Ie, ex-vivo gene therapy).

  Preferably, the promoter utilized by the nucleic acid construct of the present invention is active in the particular cell population transformed. Examples of cell type specific and / or tissue specific promoters include albumin which is liver specific (Pinkert et al., (1987) Genes Dev. 1: 268-277), lymphatic specific promoter (Calame et al. , (1988) Adv. Immunol. 43: 235-275), in particular, T cell receptors (Winoto et al., (1989) EMBO J. 8: 729-733) and immunoglobulins (Banerji et al. (1983). (Cell 33729-740) promoter, neuron specific promoter such as neurofilament promoter (Byrne et al. (1989) Proc. Natl. Acad. Sci. USA 86: 5473-5477), pancreas specific promoter Such as a mammary gland specific promoter such as the data promoter (Edrunch et al. (1985) Science 230: 912-916) or the whey promoter (US Pat. No. 4,873,316 and European Patent Application No. EP 264,166) Promoter is included.

  Examples of suitable constructs include pcDNA3, pcDNA3.1 (+/-), pGL3, PzeoSV2 (+/-), pDisplay, pEF / myc / cyto, pCMV / myc / cyto (Invitrogen Co. (www. Invitrogen, respectively). Commercially available from .com) but are not limited thereto. Examples of retroviral vectors and packaging systems are described by Clontech, San Diego, Calif. And Retro-X vectors pLNCX and pLXSN, which are commercially available and can be cloned into multiple cloning sites and the transgene is transcribed by a CMV promoter. Also included are vectors derived from Mo-MuLV such as pBabe, in which the transgene is transcribed from the 5 'LTR promoter.

  Currently preferred in vivo nucleic acid transfer techniques include transfection with viral or non-viral constructs such as adenovirus, lentivirus, herpes simplex virus I, or adeno-associated virus (AAV) and lipid based systems. Lipids useful for lipid-mediated gene transfer are, for example, DOTMA, DOPE, and DC-Chol (Tonkinson et al., Cancer Investigation, 14 (1): 54-65 (1996)). The most preferred constructs for use in gene therapy are viruses, most preferably adenovirus, AA, lentivirus, or retrovirus. The viral construct, such as a retroviral construct, may be at least one transcriptional promoter / enhancer or locus-defining element (s), or other such as alternative splicing, nuclear RNA transport, or post-translational modification of messengers. Includes other elements that regulate gene expression by means. Such vector constructs also contain packaging signals appropriate for the virus used, long terminal repeats (LTRs) or parts thereof, and plus and minus strand primer binding sites, if not already present in the virus construct. In addition, such constructs typically include a signal sequence for secretion of the peptide from the host cell in which it is placed. Preferably, the signal sequence for this purpose is a mammalian signal sequence or a signal sequence of a polypeptide variant of the invention. Optionally, the construct may also include a signal that directs polyadenylation, as well as one or more restriction sites and a translation termination sequence. As an example, such a construct typically comprises a 5 'LTR, a tRNA binding site, a packaging signal, a double stranded DNA synthesis source, and a 3' LTR or part thereof. Other non-viral vectors such as cationic lipids, polylysine and dendrimers can be used.

  It will be appreciated that the method can also be performed by specific endogenous upregulation of the expression of a splice variant of the invention in a subject. Agents for upregulation of the endogenous expression of specific splice variants of a given gene include antisense oligonucleotides directed to the splice site of interest, thereby altering the splicing pattern of the gene. This approach is described in Bcl-x (Taylor (1999) Nat. Biotechnol. 17: 1097-1100; and Mercatante (2001) J. Biol. Chem. 276: 16411-16417), IL-5R (Karras (2000) Mol. Pharmacol. 58: 380-387) and c-myc (Giles (1999) Antisense Acid Drug Dev. 9: 213-220) have been successfully used to alter the balance of expression of the two isoforms.

  For example, interleukin 5 and its receptor play an important role as regulators of hematopoiesis and as mediators in several inflammatory diseases such as allergy and asthma. Two alternatively spliced isoforms are generated from the IL-5R gene and each contain exon 9 (i.e. long form) and are excluded (i.e. short form). The long form encodes an intact membrane bound receptor, and the shorter form encodes a secreted soluble nonfunctional receptor. Using 2'-O-MOE-oligonucleotides specific for the exon 9 region, Karas and co-workers (above) significantly reduce wild type receptor expression and express shorter isoforms It could be increased. The design and synthesis of oligonucleotides that can be used in the present invention are described below, according to Sazani and Kole (2003) Progress in Molecular and Subcellular Biology 31: 217-239.

  Preferably, at least one expression (or activity) of the polypeptide variant of the invention can be treated by an agent capable of specifically downregulating.

  Oligonucleotides, such as those described in more detail below, can be used to downregulate the expression of therapeutic protein variants of the invention.

  siRNA molecules-Small interfering RNA (siRNA) molecules can be used to downregulate the expression of therapeutic protein variants of the invention. RNA interference is a two step process. In the first step, called the initial step, the input dsRNA is digested into small interfering RNAs (siRNAs) of 21-23 nucleotides (nt), which may be dicer (possibly in an ATP-dependent manner, dsRNA (direct or transgene) Or by the action of a RNase III family member of a dsRNA-specific ribonuclease that processes (cleases) introduced by the virus. Successive cleavage breaks the RNA into 19-21 bp duplexes (siRNAs) each having a 2-nucleotide 3 'overhang (Hutvagner and Zamore Curr. Opin. Genetics and Development 12: 225-232 (2002) And Bernstein Nature 409: 363-366 (2001)).

  In the effector step, the siRNA duplex binds to the nuclease complex to form an RNA-induced silencing complex (RISC). Activation of RISC requires ATP-dependent unwinding of the siRNA duplex. The active RISC then targets the homologous transcript by base pairing interactions and cleaves the mRNA into a 12 nucleotide fragment from the 3 'end of the siRNA (Hutvagner and Zamore Curr. Opin. Genetics and Development 12: 225-232 Hammond et al. (2001) Nat. Rev. Gen. 2: 110-119 (2001); and Sharp Genes. Dev. 15: 485-90 (2001)). Although the cleavage mechanism has not been elucidated as before, studies have shown that each RISC contains one siRNA and one RNase (Hutvagner and Zamore Curr. Opin. Genetics and Development 12: 225-232 (2002) ).

  The remarkable ability of RNAi suggests an amplification step within the RNAi pathway. Amplification may occur by copying of the input dsRNA or replication of the formed siRNA, which would result in a larger number of siRNAs. Alternatively or additionally, it may be replicated by multiple RISC turnover events (Hammond et al. Nat. Rev. Gen. 2: 110-119 (2001), Sharp Genes. Dev. 15: 485-90 (2001); Hutvagner and Zamore Curr. Opin. Genetics and Development 12: 225-232 (2002)). For more information on RNAi, see the following overview: Tuschl ChemBiochem. 2: 239-245 (2001); Cullen Nat. Immunol. 3: 597-599 (2002); and Brantl Biochem. Biophys. Act. 1575: 15-25 (2002).

  RNAi molecules suitable for use in the present invention can be synthesized as follows. First, the mRNA sequence is scanned downstream of the AUG start codon for AA dinucleotide sequences. The occurrence of each AA and 3 'adjacent 19 nucleotides is recorded as potential siRNA target sites. Preferably, siRNA target sites are selected from the open reading frame, as the untranslated region (UTR) is enriched in more regulatory protein binding sites. UTR binding proteins and / or translation initiation complexes can inhibit the binding of the siRNA endonuclease complex (Tuschl ChemBiochem. 2: 239-245). As shown for GAPDH, siRNA directed to the 5 'UTR mediates an approximately 90% reduction of cellular GAPDH mRNA and causes complete loss of protein levels (www.ambion.com/techlib/tn/91/912.html) Thus, it is recognized that siRNA directed to the untranslated region may also be effective.

  Second, using any sequence alignment software, such as BLAST software available from the NCBI server (www. Ncbi. Nlm. Nih. Gov / BLAST /), potential target sites are placed in an appropriate genomic database (eg, Compare with human, mouse, rat etc). The putative target sites showing significant homology to other coding sequences are filtered out.

  A suitable target sequence is selected as a template for siRNA synthesis. A preferred sequence is one with a low G / C content, as the effect of gene silencing has been shown to be higher compared to sequences with a G / C content above 55%. Preferably, several target sites are selected along the length of the target gene for evaluation. Target sites are selected from the unique nucleotide sequences of each polynucleotide of the invention such that each polynucleotide is specifically downregulated. It is preferable to use a combination of negative controls for better evaluation of the selected siRNA. Negative control siRNA preferably comprises the same nucleotide composition as the siRNA but lacks significant homology to the genome. Thus, it is preferred to use a siRNA sized nucleotide sequence if it does not show significant homology to any other gene.

  DNAzyme Molecules-Another agent capable of downregulating expression of the polypeptide of the invention is a DNAzyme molecule capable of specifically cleaving the mRNA transcript or DNA sequence of the polynucleotide of the invention. DNAzyme is a single-stranded polynucleotide capable of cleaving both single-stranded and double-stranded target sequences (Breaker, R. R. and Joyce, G. Chemistry and Biology 1995; 2: 655; Santoro , S. W. & Joyce, G. F. Proc. Natl, Acad. Sci. USA 1997; 943: 4262). A general model of the DNAzyme ("10-23" model) has been proposed. The "10-23" DNAzyme has a catalytic domain of 15 deoxyribonucleotides flanked by two substrate recognition domains of 7 to 9 of each deoxyribonucleotide. This DNAzyme type can effectively cleave the substrate RNA at the purine: pyrimidine junction (for a summary of the DNAzymes (Santoro, S. W. & Joyce, G. F. Proc. Natl, Acad. Sci. USA 199, DNAzymes) , Khachigian, LM [Curr Opin MoI Ther 4: 119-21 (2002)).

  The target site of the DNAzyme is selected from the unique nucleotide sequence of each polynucleotide of the invention such that each polynucleotide specifically downregulates.

  Examples of construction and amplification of synthesized engineered DNAzyme-recognized single- and double-stranded target cleavage sites are described by Joyce et al. U.S. Pat. No. 6,326,174, which is assigned to the assignee of the present invention. A similarly designed DNAzyme directed against the human urokinase receptor has recently been shown to inhibit urokinase receptor expression and successfully inhibit metastasis of colon cancer cells in vivo (Itoh et al, 20002, Abstract 409) , Ann Meeting Am Soc Gen Ther www.asgt.org). In another application, DNAzymes complementary to the bcr-abl oncogene successfully inhibited oncogene expression in leukocytes and reduced the rate of recurrence in autologous bone marrow grafts in the case of CML and ALL.

  Antisense Molecules-The polynucleotides of the present invention can also be downregulated by the use of individualized antisense polynucleotides that specifically hybridize to mRNA transcripts encoding the polypeptide variants of the present invention.

  As used herein, the term "antisense" refers to any composition comprising a nucleotide sequence that is specifically complementary to a DNA or RNA sequence.

  The term "antisense strand" is used in reference to a nucleic acid strand that is complementary to the "sense" strand. Antisense molecules also include peptide nucleic acids, and can be produced by any method involving synthesis or transcription. Once transferred to the cell, the complementary nucleotides combine with the natural sequence produced by the cell to form a duplex, blocking either transcription or translation. The term "negative" is often used in reference to the antisense strand, and "positive" is often used in reference to the sense strand. Antisense oligonucleotides are also used for in vivo alternative splicing modifications and in vivo and in vitro diagnostics (Khelifi C. et al., 2002, Current Pharmaceutical Design 8: 451-1466; Sazani, P., and Kole. R. Progress in Molecular and Cellular Biology, 2003, 31: 217-239).

  Antisense molecules can be designed that can be used to effectively downregulate expression of the polypeptides of the invention taking into account the following two aspects important to the antisense approach. The first aspect is the delivery of the oligonucleotide to the cytoplasm of a suitable cell, and the second aspect is the design of the oligonucleotide to which the designed mRNA specifically binds in the cell in a manner that inhibits its translation. It is.

  The prior art teaches a number of delivery strategies that can be used to effectively deliver oligonucleotides to a wide variety of cell types (eg, Luft J Mol Med 76: 75-6 (1998); Kronenwett et al. Blood 91: 852-62 (1998); Rajur et al. Bioconjug Chem 8: 935-40 (1997); Lavigne et al. Biochem Biophys Res Commun 237: 566-71 (1997) and Aoki et al. (1997) Biochem Biophys Res Commun 231: 540-5 (1997)).

  In addition, algorithms are available to identify sequences with the highest putative binding affinity for the target mRNA based on thermodynamic cycles that reveal the energy of structural changes in both the target mRNA and the oligonucleotide (eg, , Walton et al. Biotechnol Bioeng 65: 1-9 (1999)).

  Such an algorithm has been successfully used to implement an antisense approach in cells. For example, Walton et al. The algorithm developed by J., has allowed scientists to successfully design antisense oligonucleotides of rabbit β-globin (RBG) and mouse tumor necrosis factor α (TNFα) transcripts. The same research group has recently been evaluated by kinetic PCR techniques and shows that the oligonucleotides selected rationally against three model target mRNAs (human lactate dehydrogenase A and B and rat gp130) in cell culture. We report that the sense activity was proved to be effective in almost all cases, including tests to target three different targets in two cell types with phosphodiester and phosphorothioate oligonucleotide chemistry. ing.

  In addition, several approaches for designing and predicting the efficacy of specific oligonucleotides using in vitro systems have also been published (Matveeva et al., Nature Biotechnology 16: 1374-1375 (1998)).

  Several clinical trials have demonstrated the safety, feasibility, and activity of antisense oligonucleotides. For example, antisense oligonucleotides suitable for cancer treatment have been successfully used (Holmund et al., Curr Opin MoI Ther 1: 372-85 (1999)), while c-myb gene, p53, and Bcl. The treatment of hematologic malignancies with antisense oligonucleotides targeting -2 has entered clinical trials and has been found to be tolerated by patients (Gerwitz Curr Opin MoI Ther 1: 297-306 (1999)).

  More recently, antisense-mediated suppression of heparanase gene expression has been reported to inhibit pleural dissemination of human cancer cells in mouse models (Uno et al., Cancer Res 61: 7855-60 (2001)).

  Thus, recent developments in the area of antisense technology described above result in high precision antisense design algorithms and a wide variety of oligonucleotide delivery systems, known to those skilled in the art without undue testing and erroneous experimentation. It is now recognized that appropriate antisense approaches can be designed and implemented to downregulate the expression of sequences.

  The target site of the antisense molecule is selected from the unique nucleotide sequence of each polynucleotide of the invention such that each polynucleotide is specifically downregulated.

  Ribozyme-Another agent capable of downregulating polypeptide expression of the invention is a ribozyme molecule capable of specifically cleaving mRNA transcripts encoding a polypeptide variant of the invention. Ribozymes are increasingly used for sequence-specific inhibition of gene expression by cleavage of mRNA encoding a protein of interest (Welch et al., Curr Opin Biotechnol. 9: 486-96 (1998)). The possibility of designing ribozymes to cleave any specific target RNA makes them valuable tools in both basic research and therapeutic applications. In the therapeutic area, ribozymes have been used to target viral RNA in infections, dominant oncogenes in cancer, and specific somatic mutations in genetic disorders (Welch et al., Clin Diagn Virol. 10: 163 -71 (1998)). Most notably, some ribozyme gene therapy protocols for HIV patients are already in Phase I trials. More recently, ribozymes have been used for transgenic animal studies, validation of gene targets, and elucidation of pathways. Several ribozymes are in various clinical trials. ANGIOZYME was the first synthetic ribozyme to be studied in human clinical trials. ANGIOZYME specifically inhibits VEGF-r (the formation of vascular endothelial growth factor receptor, an important component in the angiogenic pathway) Ribozyme Pharmaceuticals, Inc. and other companies are important for anti-angiogenic therapy in animal models A ribozyme designed to selectively destroy HEPTAZYME (Hepatitis C virus (HCV) RNA was found to be effective in reducing Hepatitis C virus RNA in cell culture assays. (Ribozyme Pharmaceuticals, Incorporated-WEB homepage).

  Alternatively, a polypeptide variant of the invention may be made using a downregulator such as an antibody or antibody fragment (ie a neutralizing antibody) capable of specifically binding to the polypeptide of the invention and inhibiting its activity. Can be downregulated at the polypeptide level. Such antibodies can, for example, be directed to the heterodimerization domain or putative ligand binding domain on the variant. Further descriptions of antibodies and methods of generating antibodies are provided below.

Pharmaceutical compositions and their delivery The invention features pharmaceutical compositions comprising a therapeutically effective amount of a therapeutic of the invention, which is preferably a therapeutic protein variant as described herein. Optionally and alternatively, the therapeutic agent may be an antibody or oligonucleotide that specifically recognizes and binds a therapeutic protein variant but not to a corresponding known full-length protein.

  Alternatively, the pharmaceutical composition of the invention comprises at least an active portion of a therapeutically effective amount of a therapeutic protein variant polypeptide.

  It is preferred to use the pharmaceutical composition of the invention for the treatment of cluster related diseases.

  "Treatment" refers to therapeutic treatment and prophylactic or preventative measures. Those in need of treatment include those already with the disorder and those in which the disorder is to be prevented. Thus, the mammal to be treated herein may be diagnosed as suffering from a disorder or may be susceptible to or suspected of being a disorder. A "mammal" for therapeutic purposes is any animal classified as a mammal, including humans, livestock, zoo animals, competition animals, or pets (such as dogs, horses, cats, cows, etc.) Say Preferably, the mammal is a human.

  A "disorder" is any condition that would benefit from treatment with an agent of the present invention. This includes chronic and acute disorders or diseases, including those pathological conditions which predispose a mammal to the disorder in question. Non-limiting examples of disorders to be treated herein are described with respect to the specific examples described herein.

  The term "therapeutically effective amount" refers to the amount of an agent of the invention that effectively treats a disease or disorder in a mammal. In the case of cancer, a therapeutically effective amount of the drug reduces the number of cancer cells, reduces the size of the tumor, and inhibits invasion of the cancer cells into surrounding tissues (ie, some delay, preferably arresting, of spread). Inhibits tumor metastasis (ie, slows, preferably arrests) spread, inhibits some growth of tumor growth, and / or some spread of one or more symptoms associated with cancer It can be relaxed. To the extent the drug can prevent the growth of existing cancer cells and / or kill it, it can exhibit cytostatic and / or cytotoxic properties. For cancer therapy, efficacy can be measured, for example, by assessment of disease progression (TTP) and / or determination of response rate (RR).

  The therapeutic agents of the present invention can be administered to the subject itself, or can be administered as part of a pharmaceutical composition mixed with a pharmaceutically acceptable carrier.

  As used herein, a "pharmaceutical composition" is one or more of the active ingredients described herein, including other chemical ingredients such as physiologically relevant carriers and excipients. It refers to a preparation. The purpose of a pharmaceutical composition is to facilitate administration of a compound to an organism.

  The term "active ingredient" as described herein refers to a preparation responsible for biological effects.

  Hereinafter, the phrases "physiologically acceptable carrier" and "pharmaceutically acceptable carrier", which can be used interchangeably, do not cause significant inflammation in the organism and are biologically active and and of the compounds administered. Carrier or diluent that does not invalidate the property. Adjuvants are included in these phrases. One of the components included in the pharmaceutically acceptable carrier may be, for example, polyethylene glycol (PEG) (a biocompatible polymer exhibiting wide solubility in both organic and aqueous media) (Mutter et al. (1979).

  The term "excipient" as used herein refers to an inert substance added to a pharmaceutical composition to further facilitate administration of the active ingredient. Examples of non-limiting excipients include calcium carbonate, calcium phosphate, various sugar and starch types, cellulose derivatives, gelatin, vegetable oils and polyethylene glycols.

  Drug formulation and administration techniques are described in "Remington's Pharmaceutical Sciences," Mack Publishing Co. , Easton, PA, latest edition (incorporated herein by reference).

  Suitable routes of administration include, for example, oral, rectal, transmucosal (in particular, nasal, enteral), or parenteral delivery (including intramuscular, subcutaneous and intraspinal), and intrathecal, direct intracerebroventricular Intravenous, intraperitoneal, intranasal, or intraocular injection. Alternatively, rather than being in a systemic fashion, the preparation can be administered locally, for example, by injection of the preparation directly into a specific area of the patient's body.

  The pharmaceutical compositions of the invention may be manufactured by processes well known in the art, such as conventional mixing, dissolving, granulating, dragee-making, powdering, emulsifying, encapsulating, entrapping or lyophilizing processes. it can.

  One or more physiologically acceptable including excipients and auxiliaries that facilitate the processing of the active ingredient into a pharmaceutically usable preparation of the pharmaceutical composition used in the present invention Can be formulated in a conventional manner using different carriers. Proper formulation is dependent upon the route of administration chosen.

  For injection, the active ingredient of the present invention can be formulated in an aqueous solution, preferably a physiologically compatible buffer such as Hanks's solution, Ringer's solution, or saline. For transmucosal administration, penetrants appropriate to the barrier to be permeated are used in the formulation. Such penetrants are known in the art.

  For oral administration, the compounds can be formulated readily by combining the active compounds with pharmaceutically acceptable carriers well known in the art. Such carriers enable the compounds of the invention to be formulated as tablets, pills, dragees, capsules, liquids, gels, syrups, suspensions, and the like, for ingestion by the patient. Solid excipients can be used to make a pharmacological preparation for oral use, and optionally, the resulting mixture is milled and, if desired, subsequently granulated with the addition of suitable auxiliaries The mixture can be processed to obtain tablets or dragee cores. Suitable excipients are, in particular, fillers such as sugars, including lactose, sucrose, mannitol or sorbitol, eg corn starch, wheat starch, rice starch, potato starch, gelatine, tragacanth gum, methylcellulose, hydroxypropyl Cellulose preparations such as methylcellulose, sodium carbomethylcellulose and / or physiologically acceptable polymers such as polyvinylpyrrolidone (PVP). If desired, disintegrating agents may be added, such as crosslinked polyvinyl pyrrolidone, agar, or alginic acid or a salt thereof such as sodium alginate.

  The dragee core is obtained using a suitable coating. For this purpose, optionally using concentrated sugar solutions which may comprise gum arabic, talc, polyvinyl pyrrolidone, carbopol gel, polyethylene glycol, titanium dioxide, lacquer liquids and suitable organic solvents or solvent mixtures Can. Dyestuffs or pigments may be added to the tablets or dragee coatings for identification or characterization of different combinations of active compound doses.

  Pharmaceutical compositions that can be used orally include push-fit capsules made of gelatin and soft gelatin, and sealed capsules made of gelatin and a plasticizer, such as glycerol or sorbitol. Push-fit capsules can comprise the active ingredient in admixture with a filler such as lactose, a binder such as starch, a lubricant such as talc or magnesium stearate, and optionally a stabilizer. In soft capsules, the active ingredient can be dissolved or suspended in suitable liquids, such as fatty oils, liquid paraffin, or liquid polyethylene glycols. In addition, stabilizers can be added. All formulations for oral administration should be in dosages suitable for the chosen route of administration.

  For buccal administration, the compositions can take the form of tablets or lozenges formulated in a conventional manner.

  For administration by nasal inhalation, the active ingredient used in the present invention can be pressurized packed with a suitable propellant (eg dichlorodifluoromethane, trichlorofluoromethane, dichloro-tetrafluoroethane or carbon dioxide) or It is conveniently delivered in the form of an aerosol spray preparation derived from a sprayer. In the case of a pressurized aerosol, the dosage unit can be determined by providing a valve to deliver a metered amount. Capsules and cartridges of, eg, gelatin for administration can be formulated containing a powder mix of the compound and a suitable powder base such as lactose or starch.

  The preparations described herein can be formulated for parenteral administration, eg, by bolus injection or continuous infusion. Formulations for injection may be present in unit dosage form (eg, ampoules or multiple dose containers), optionally with an added preservative. The compositions may be suspensions, solutions or emulsions of oily or aqueous vehicles, and may contain formulatory agents such as suspending, stabilizing and / or dispersing agents.

  Pharmaceutical compositions for parenteral administration include aqueous solutions of the active preparation in water-soluble form. Additionally, suspensions of the active ingredients can be prepared as appropriate oily or water based suspensions. Suitable lipophilic solvents or vehicles include fatty oils such as sesame oil or synthetic fatty acid esters such as ethyl oleate, triglycerides, or liposomes. Aqueous injection suspensions may contain substances that increase the viscosity of the suspension, such as sodium carboxymethyl cellulose, sorbitol, or dextran. Optionally, the suspension may also contain suitable stabilizers or agents which increase the solubility of the active ingredients in order to prepare a highly concentrated solution.

  Alternatively, the active ingredient may be in powder form for constitution with a suitable vehicle, such as a sterile, pyrogen-free solution, before use.

  The preparations of the present invention can also be formulated in rectal compositions such as suppositories or retention enemas, using, for example, conventional suppository bases such as cocoa butter or other glycerides.

  Pharmaceutical compositions suitable for use in the context of the present invention include compositions comprising an effective amount of the active ingredient to achieve the intended purpose. More specifically, a therapeutically effective amount means an amount of the active ingredient effective to prevent, alleviate or ameliorate the symptoms of the disease or prolong the survival of the subject being treated.

  Determination of a therapeutically effective amount is well within the ability of one of ordinary skill in the art.

  For any preparation used in the methods of the invention, the therapeutically effective amount or dose can be estimated initially from in vitro assays. For example, doses can be determined in animal models and such information can be used to more accurately determine useful doses in humans.

  The toxicity and therapeutic efficacy of the active ingredients described herein can be determined by standard pharmaceutical procedures in vitro, cell culture, or experimental animals. The data obtained from these in vitro and cell culture assays and animal studies can be used in the determination of dosage ranges for use in humans. The dosage may vary depending upon the dosage form employed and the route of administration utilized. The exact formulation, route of administration and dosage can be chosen by the individual physician in view of the patient's condition (see, eg, Fingl, et al., 1975, in "The Pharmacologic Basis of Therapeutics", Ch. 1) See p. 1).

  Depending on the severity and responsiveness of the condition to be treated, administration may be single or multiple doses, and treatment may continue for several days to several weeks or until healing or relief of the condition is achieved. it can.

  The amount of composition administered will, of course, be dependent on the subject being treated, on the severity of the affliction, on the manner of administration and on the judgment of the attending physician.

  A composition comprising a preparation of the invention formulated in a compatible pharmaceutical carrier can be prepared for treatment of the applied condition, placed in a suitable carrier and labeled.

  The pharmaceutical compositions of the invention may, if desired, be packaged in a pack or dispensing device such as an FDA approved kit which may contain one or more unit dosage forms containing the active ingredient. The pack may, for example, comprise metal or plastic foil (such as a blister pack). The pack or dispenser may also be adapted to the notification accompanying the container in the form prescribed according to the regulations on the manufacture, use or sale of medicines by government agencies, the notification may be in the form of a composition or to a human or animal. Reflect government approval for the administration of Such notification may be, for example, an insert of a labeled or approved product approved by the U.S. Food and Drug Administration for prescription of a drug.

Immunogenic Compositions The therapeutic agents of the invention may optionally be molecules that promote a specific immunogenic response in the subject to at least one of the polypeptides of the invention. The molecule may be a polypeptide variant of the invention, a fragment derived therefrom, or a nucleic acid sequence encoding the same. While such molecules can be administered to the subject itself, it is preferred to administer the agent in combination with an immunostimulatory agent in an immunogenic composition. The immunostimulatory agent can be any substance that enhances or potentiates the immune response (antibody and / or cell mediated) to the exogenous antigen. Examples of immunostimulatory agents include adjuvants into which the compound is incorporated, biodegradable microspheres (eg, polylactide galactide), and liposomes (see, eg, US Pat. No. 4,235,877). Vaccine preparations are generally, for example, M. F. Powell and M. J. Newman, eds. , "Vaccine Design (the subunit and adjuvant approach)," Plenum Press (NY, 1995).

  Exemplary immunogenic compositions can include DNA encoding one or more of the above polypeptides, such that the polypeptide is generated in situ. The DNA may be present in any of a variety of delivery systems known to those skilled in the art, including nucleic acid expression systems (see below), bacterial and viral expression systems. A number of gene delivery technologies (such as those described in Rolland, Crit. Rev. Therap. Drug Carrier Systems 15: 143- 198, 1998 and references therein) are well known in the art. Suitable nucleic acid expression systems include DNA sequences necessary for expression in a subject, such as appropriate promoters and termination signals. Bacterial delivery systems involve the administration of bacteria (such as Calmette-Guerin bacteria) that express an immunogenic portion of the polypeptide on its cell surface or secrete such an epitope. In a preferred embodiment, the DNA can be transferred using a viral expression system (eg vaccinia or other pox virus, a retrovirus, or an adenovirus), and the use of a non-pathogenic (defective) replication competent virus May be included. Suitable systems are described, for example, by Fisher-Hoch et al. , Proc. Natl. Acad. Sci. USA 86: 317-321, 1989; Flexner et al. , Ann. N. Y Acad. Sci. 569: 86-103, 1989; Flexner et al. Vaccine 8: 17-21, 1990; U.S. Pat. Nos. 4,603,112, 4,769,330, and 5,017,487, WO 89/01973; U.S. Pat. British Patent No. 2,200,651; European Patent No. 0,345,242; WO 91/02805; Berkner, Biotechniques 6: 616-627, 1988; Rosenfeld et al. , Science 252: 431-434, 1991; Kolls et al. , Proc. Natl. Acad. Sci. USA 91: 215-219, 1994; Kass-Eisler et al. , Proc. Natl. Acad. Sci. USA 90: 11498-11502, 1993; Guzman et al. , Circulation 88: 2838-2848, 1993; and Guzman et al. , Cir. Res. 73: 1202-1207, 1993. Techniques for incorporating DNA into such expression systems are well known to those skilled in the art. See, for example, Ulmer et al. The DNA can also be "naked", as described in, Science 259: 1745-1749, 1993, and outlined in Cohen, Science 259: 1691-1692, 1993. Uptake of naked DNA can be increased by coating the DNA on biodegradable beads and effectively transporting it to cells.

  It will be appreciated that the immunogenic composition can comprise both polynucleotide and polypeptide components. Such immunogenic compositions can enhance the immune response.

  Any of a variety of immunostimulatory agents can be used in the immunogenic compositions of the present invention. For example, an adjuvant can be included. Most adjuvants include substances designed to protect the antigen from rapid metabolism (aluminum hydroxide or mineral oil) and stimulators of the immune response (such as lipid A, proteins from B. pertussis or M. tuberculosis). Suitable adjuvants are, for example, Freund's incomplete and complete adjuvants (Difco Laboratories, Detroit, Mich.), Merck adjuvant 65 (Merck and Company, Inc., Rahway, NJ), AS-2 (SmithKline Beecham). (Philadelphia, Pa.), Aluminum salts such as aluminum hydroxide gel (alum) or aluminum phosphate, calcium salts, salts of iron or zinc, insoluble suspensions of acylated tyrosines, acylated sugars, cationic or anions It is commercially available as sex derived polysaccharides, polyphosphazenes, biodegradable microspheres, monophosphoryl lipids A and quiA. GM-CSF or cytokines such as interleukin-2, -7 or -12 can also be used as an adjuvant.

  Adjuvant compositions can be designed to predominantly induce Th1-type immune responses. High levels of Th1-type cytokines (e.g. IFN- [gamma], TNF- [alpha], IL-2 and IL-12) tend to induce a cellular immune response against the administered antigen. In contrast, high levels of Th2-type cytokines (eg, IL-4, IL-5, IL-6, and IL-10) tend to induce humoral immunity. Following application of the immunogenic compositions described herein, the subject supports an immune response that induces a Th1-type response and a Th2-type response. The levels of these cytokines can be easily assessed using standard assays. For a review of the cytokine family, see Mosmann and Coffinan, Ann. Rev. Immunol. 7: 145-173, 1989.

  Preferred adjuvants for use in predominantly eliciting a Th1-type response include, for example, a combination of monophosphoryl lipid A (preferably 3-de-O acylated monophosphoryl lipid A (3D- MPL)) and an aluminum salt. Be MPL adjuvants are commercially available from Corixa Corporation (Seattle, Wash., US Pat. Nos. 4,436,727, 4,877,611, 4,866,034, and 4, See 912, 094). CpG-containing oligonucleotides (CpG dinucleotides are unmethylated) also predominantly induce Th1 responses. Such oligonucleotides are well known in the art and are described, for example, in WO 96/02555, WO 99/33488, and U.S. Patent Nos. 6,008,200 and 5,856,462. . Immunostimulatory DNA sequences are also described, for example, by Sato et al. , Science 273: 352, 1996. Another preferred adjuvant is saponin (preferably, QS21 (Aquila Biopharmaceuticals Inc., Framingham, Mass.)), Which can be used alone or in combination with other adjuvants. For example, the enhanced system is a combination of monophosphoryl lipid A and a saponin derivative (a combination of QS21 and 3D-MPL described in WO 94/00153 or a cholesterol-suppressed Q21 described in WO 96/33739) (Eg, combinations with low reactivity). Other preferred formulations include oil-in-water emulsions and tocopherols. Particularly potent adjuvant formulations comprising an oil-in-water emulsion comprising QS21, 3D- MPL and tocopherol are described in WO 95/17210.

  Other preferred adjuvants include Montanide ISA 720 (Seppic, France), SAF (Chiron, Calif., United States), ISCOMS (CSL), MF-59 (Chiron), adjuvants of the SBAS series (eg SmithKline Beecham, Rixensart) , SBAS-2 or SBAS-4 commercially available from Belgium, Detox (Corixa, Hamilton, Mont.), RC-529 (Corixa, Hamilton, Mont.), And other aminoalkyl glucosaminide tetraphosphates (Corixa, Hamilton, Mont.) AGP) (such as those described in copending U.S. patent application Ser. Nos. 08 / 853,826 and 09 / 074,720).

  Delivery vehicles can be used within the immunogenic compositions of the invention to facilitate antigen-specific immune responses that target tumor cells. Delivery vehicles include antigen presenting cells (APCs) (dendritic cells, macrophages, B cells, monocytes etc) and other cells that can be engineered to make APC efficient. Such cells increase antigen presentation capacity, improve activation and / or maintenance of T cell responses, have anti-tumor effects per se and / or become immunologically compatible with the receiver It can be genetically engineered. APCs can generally be isolated from any of a variety of biological fluids, including tumors and tumor surrounding tissues, which can be autologous cells, allogeneic cells, syngeneic cells, or xenogeneic cells.

  Dendritic cells are very potent APCs (Banchereau and Steinman, Nature 392: 245-251, 1998) and have been shown to be effective as physiological adjuvants for inducing prophylactic or therapeutic anti-tumor immunity (See Timmernan and Levy, Ann. Rev. Med. 50: 507-529, 1999). In general, dendritic cells have their typical shape (star shape in situ, outstanding cytoplasmic processes (dendrites observed in vitro)), efficient antigen uptake, processing, and presentation capabilities, and naive It can be identified based on its ability to activate T cell responses. Dendritic cells can, of course, be engineered to express specific cell surface receptors or ligands not commonly found on dendritic cells in vivo or ex vivo, such modified dendritic cells Is contemplated by the present invention. As an alternative to dendritic cells, antigen-loaded dendritic cells (called exosomes), which are secretory vesicles, can be used in immunogenic compositions (Zitvogel et al., Nature Med. 4: 594-. 600, 1998)).

  Dendritic cells and precursors can be obtained from peripheral blood, bone marrow, tumor infiltrating cells, peritumoral tissue infiltrating cells, lymph nodes, spleen, skin, cord blood, or any other suitable tissue or fluid. For example, ex vivo differentiation of dendritic cells by adding a combination of cytokines such as GM-CSF, IL-4, IL-13, and / or TNFα to cultures of monocytes collected from peripheral blood it can. Alternatively, differentiation of GM-CSF, IL-13, TNFα, CD40 ligand, LPS, flt3 ligand, and / or dendritic cells into culture solution, CD34 positive cells collected from peripheral blood, umbilical cord blood, or bone marrow may be matured. And dendritic cells can be differentiated by the addition of a combination of other compounds that induce proliferation.

  Dendritic cells are classified into "immature" cells and "mature" cells, which are distinguished by a simple method into two well- characterized phenotypes. Immature dendritic cells are characterized as APCs with high antigen uptake and processing capacity, which correlates with high Fcy receptor and mannose receptor expression. The mature phenotype is typically a lower expression of these markers but cell surface molecules responsible for T cell activation such as class I and class II MHC, adhesion molecules (eg CD54 and CD11), and co-expression Expression of stimulatory molecules (e.g., CD40, CD80, CD86, and 4-1BB) is characterized by high expression.

  The APCs can generally be transfected with at least one polynucleotide encoding a polypeptide of the invention such that variant II or an immunogenic portion thereof is expressed on the cell surface. Such transfection can occur ex vivo, and as described herein, compositions comprising such transfected cells can be used for therapeutic purposes. Alternatively, gene delivery agents that target dendritic cells or other antigen presenting cells can be administered to a subject and transfection can occur in vivo. For example, in vivo and ex vivo transfection of dendritic cells can be performed according to any method known in the art (the method described in WO 97/24447 or Mahvi et al., Immunology and cell Biology 75: 456-460, 1997). It can be done using the gene gun approach as described in. Dendritic cells or progenitor cells and the polypeptides of the invention, DNA (naked or in a plasmid vector) or RNA or recombinant bacteria or virus expressing an antigen (eg vaccinia, fowlpox virus, adenovirus or lentivirus vector) The antigen loading of dendritic cells can be performed by incubation of Prior to loading, the polypeptide can be covalently linked to an immunological partner to obtain T cell help (eg, a carrier molecule) such as those described above. Alternatively, dendritic cells can be pulsed with unconjugated immunological partners, either individually or in the presence of a polypeptide.

  It will be appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention which are, for clarity, described in one embodiment, may also be provided separately or in any suitable subcombination.

  Although the invention has been described in conjunction with specific embodiments thereof, it is evident that many alternatives, modifications and variations will be apparent to those skilled in the art. Accordingly, it is intended to embrace all such changes, modifications and variations that fall within the spirit and scope of the appended claims. All publications, patents, and patent applications cited herein are hereby incorporated by reference as if each publication, patent and patent application were specifically and individually incorporated herein by reference. The same range is incorporated herein by reference in its entirety. Moreover, citation and identification of any reference herein should not be construed as being usable as prior art to the present invention.

BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 shows a summary of the cancer biomarker selection engine and the wet validation step. FIG. 5 is a schematic showing the classification of transcripts of a given contig based on the presence or absence of unique sequence regions. FIG. 1 shows a summary of the quantitative real-time PCR analysis. Figure 2 is a schematic representation of oligonucleotide based microarray construction. FIG. 1 shows a summary of the flow of oligonucleotide based microarray experiments. FIG. 17 is a histogram showing cancer versus cell line expression versus normal tissue expression for cluster H61775 showing over expression in brain malignant brain tumors and a mixture of malignancies from different tissues. FIG. 16 is a histogram showing expression of transcripts of variant 9 of the immunoglobulin superfamily member 9 variant detectable by an amplicon (H61775 transcript) as shown in the sequence name H61775seg8 in normal and cancerous lung tissue. FIG. 16 is a histogram showing the expression of the H61775 transcript of immunoglobulin superfamily member 9 detectable by the amplicon, as shown in the sequence name H61775 seg8, in different normal tissues. FIG. 16 is a histogram showing cancer versus cell line expression versus normal tissue expression for cluster M85491, showing over expression in a mixture of epithelial malignant brain tumors and malignancies from different tissues. FIG. 16 is a histogram showing the overexpression of the above Ephrin B-type receptor 2 precursor M85491 transcripts detectable by an amplicon, as set forth in SEQ ID NO: M85491 seg24 in cancerous lung samples compared to normal samples. FIG. 16 is a histogram showing the expression of Ephrin type B receptor 2 precursor (tyrosine-protein kinase receptor EPH-3) M85491 transcript as shown in the sequence name M85491 seg24 in different normal tissues, detectable by an amplicon. FIG. 16 is a histogram showing cancer versus cell line expression versus normal tissue expression for cluster T39971, showing overexpression in liver cancer, lung malignancy and pancreatic cancer. FIG. 16 is a histogram showing cancer versus cell line expression versus normal tissue expression for cluster Z21368 showing overexpression in epithelial malignant brain tumors, a mixture of malignancies from different tissues, and pancreatic cancer. FIG. 16 is a histogram showing overexpression of extracellular sulfatase Sulf-1 Z21368 transcripts detectable by an amplicon, as set forth in SEQ ID NO: Z21368 junc17-21 in cancerous lung samples compared to normal samples. FIG. 16 is a histogram showing expression of extracellular sulfatase Sulf-1 Z21 368 transcripts detectable by an amplicon as shown in the sequence name Z21 368 jun c 17-21 in different normal tissues. FIG. 10 is a histogram showing the overexpression of SUL1_HUMAN-extracellular sulfatase Sulf-1 (Z21368 transcript) detectable by an amplicon, as set forth in SEQ ID NO: Z21368 seg39 in cancerous lung samples compared to normal samples. FIG. 16 is a histogram showing the expression of SUL1_HUMAN-extracellular sulfatase Sulf-1 (Z21368 transcript) detectable by an amplicon, as shown in the sequence name Z21368 seg39 in different normal tissues. SMO2_HUMAN SPARC related modular calcium binding protein 2 receptor (secretory modular calcium binding protein 2) (SMOC-2) (smooth muscle related protein) detectable by an amplicon as shown in the sequence name Z44808junc8-11 in different normal tissues 2) Histogram showing expression of Z44808 transcript. FIG. 16 is a histogram showing overexpression of gastrin releasing peptide (HUMGRP5E) transcripts detectable by an amplicon, as set forth in the sequence name HUMGRP5Ejunc3-7 in several cancerous lung samples compared to normal samples. FIG. 16 is a histogram showing expression of gastrin releasing peptide (HUMGRP5E) transcripts detectable by amplicon as shown in the sequence name HUMGRP5Ejunc3-7 in different normal tissues. FIG. 16 is a histogram showing cancer versus cell line expression versus normal tissue expression for cluster F05068, showing over expression in uterine malignant brain tumors. FIG. 16 is a histogram showing cancer versus cell line expression versus normal tissue expression for cluster H14624, showing overexpression in colorectal cancer, epithelial malignancies, a mixture of malignancies from different tissues, lung malignant brain tumors, and pancreatic cancer. FIG. 16 is a histogram showing cancer versus cell line expression versus normal tissue expression for cluster H 38804, showing overexpression in transitional cell carcinoma, brain malignancy, a mixture of malignancy from different tissues, and gastric cancer. FIG. 16 is a histogram showing cancer versus cell line expression versus normal tissue expression for cluster HSENA 78, showing overexpression in epithelial and lung malignancies. FIG. 17 is a histogram showing cancer versus cell line expression versus normal tissue expression for cluster HUMODCA showing over expression in brain malignancies, colorectal cancer, epithelial malignancies, and a mixture of malignancies from different tissues. FIG. 16 is a histogram showing cancer versus cell line expression versus normal tissue expression for cluster R 00299 showing overexpression in lung malignancies. FIG. 16 is a histogram showing cancer versus cell line expression versus normal tissue expression for cluster Z41644, showing overexpression in lung malignancies, malignant breast cancer and pancreatic cancer. FIG. 16 is a histogram showing cancer versus cell line expression versus normal tissue expression for cluster Z44808, showing overexpression in colorectal cancer, lung cancer and pancreatic cancer. FIG. 17 is a histogram showing overexpression of SMO2_HUMANSPARC related modular calcium binding protein 2Z44808 transcripts detectable by an amplicon, as set forth in SEQ ID NO: Z44808junc8-11 in cancerous lung samples compared to normal samples. FIG. 16 is a histogram showing cancer versus cell line expression versus normal tissue expression for cluster AA 161 187, showing overexpression in a mixture of malignant brain tumors, epithelial malignancies, and malignancies from different tissues. FIG. 16 is a histogram showing cancer versus cell line expression versus normal tissue expression for cluster AA 161 187, showing over expression in a mixture of malignant brain tumors and malignancies from different tissues. FIG. 16 is a histogram showing cancer versus cell line expression versus normal tissue expression for cluster HUMCA1 XIA showing overexpression in malignant bone tumors, epithelial malignancies, mixtures of malignancies from different tissues, and lung malignancies. FIG. 16 is a histogram showing cancer versus cell line expression versus normal tissue expression for cluster HUMCEA showing overexpression in epithelial malignancies, a mixture of malignancies from different tissues, and pancreatic cancer. FIG. 16 is a histogram showing cancer versus cell line expression versus normal tissue expression for cluster R35137, showing overexpression in hepatocellular carcinoma. FIG. 16 is a histogram showing cancer versus cell line expression versus normal tissue expression for cluster Z25299, showing overexpression in malignant brain tumors, a mixture of malignancies from different tissues, and ovarian cancer. Histogram showing down-regulation of acid stable proteinase inhibitor Z25299 transcript, a secreted leukocyte protease inhibitor detectable by an amplicon, as shown in SEQ ID NO: Z25299junc13-14-21 in cancerous lung samples compared to normal samples It is. FIG. 16 is a histogram showing the downregulation of acid stable proteinase inhibitor Z25299 transcript, a secreted leukocyte protease inhibitor detectable by an amplicon, as set forth in SEQ ID NO: Z25299seg20 in cancerous lung samples compared to normal samples. FIG. 16 is a histogram showing cancer versus cell line expression versus normal tissue expression for cluster HSSTROL3, showing overexpression in transitional cell carcinoma, epithelial malignancy, a mixture of malignancies from different tissues, and pancreatic cancer. FIG. 16 is a histogram showing the overexpression of stromelysin-3 HSSTROL3 transcripts detectable by an amplicon as shown in the sequence name HSSTROL3seg24 in cancerous lung samples compared to normal samples. FIG. 16 is a histogram showing the expression of stromelysin-3 HSSTROL3 transcripts detectable by amplicon as shown in the sequence name HSSTROL3seg24 in different normal tissues. FIG. 16 is a histogram showing cancer versus cell line expression versus normal tissue expression for cluster HUMTREFAC, showing overexpression in a mixture of malignant tumors from different tissues, malignant breast cancer, pancreatic cancer and prostate cancer. FIG. 16 is a histogram showing cancer versus cell line expression versus normal tissue expression for cluster HSS100 PCBs showing over expression in a mixture of malignancies from different tissues. FIG. 16 is a histogram showing cancer versus cell line expression versus normal tissue expression for cluster HSU33147, showing over expression in a mixture of malignancies from different tissues. FIG. 16 is a histogram showing cancer versus cell line expression versus normal tissue expression for cluster R20779, showing overexpression in epithelial malignancies, a mixture of malignancies from different tissues and malignant lung tumors. FIG. 16 is a histogram showing cancer versus cell line expression versus normal tissue expression for cluster R38144 showing overexpression in epithelial malignancies, lung malignancies, skin malignancies, and gastric cancer. Histogram showing cancer versus cell line expression versus normal tissue expression for cluster HUMOSTRO showing overexpression in epithelial malignancies, a mixture of malignancies from different tissues, lung malignancy, malignancy breast cancer, ovarian cancer and skin malignancy It is. FIG. 16 is a histogram showing cancer versus cell line expression versus normal tissue expression for cluster HUMOSTRO showing overexpression in epithelial malignancies, a mixture of malignancies from different tissues, and kidney malignancies. FIG. 16 is a histogram showing the overexpression of R11723 transcripts detectable by amplicon as shown in SEQ ID NO: R11723seg13 in cancerous lung samples compared to normal samples. FIG. 16 is a histogram showing the expression of R11723 transcripts detectable by amplicon as shown in the sequence name R11723seg13 in different normal tissues. FIG. 16 is a histogram showing the overexpression of R11723 transcripts detectable by an amplicon, as set forth in SEQ ID NO: R11723junc11-18 in cancerous lung samples compared to normal samples. FIG. 16 is a histogram showing cancer versus cell line expression versus normal tissue expression for cluster R16276, showing overexpression in malignant lung tumors. FIG. 16 is a histogram showing the differential expression of six sequences H61775seg8, HUMGRP5 Ejunc3-7, M85491 Seg24, Z21368 junc17-21, HSSTROL3seg24, and Z25299seg20 in cancerous lung samples compared to normal samples. FIG. 16 is a histogram showing the differential expression of six sequences H61775seg8, HUMGRP5 Ejunc3-7, M85491 Seg24, Z21368 junc17-21, HSSTROL3seg24, and Z25299seg20 in cancerous lung samples compared to normal samples. Relative to trophinin-related protein (Tastin) [T86235] variants (eg, variants nos. 23 to 26, 31, 32) in lung samples from normal and tumor as determined by real time PCR using primers of SEQ ID NO: 1480 It is a histogram which shows expression. Trophinin-related protein (Tastin) [T86235] variants in normal and tumor-derived lung samples, as determined by microarray analysis using oligos detailed in SEQ ID NOs: 1512-1514 [e.g. 23 is a histogram showing relative expression of 23, 26, 27, 29-31, 33). 16 is a histogram showing the relative expression of Homeo box C10 (HOXC10) [N31842] variants (eg, variant # 3) in lung samples from normal and tumor as determined by real time PCR using primers of SEQ ID NO: 1517 . Relative to nucleolar protein 4 (NOL4) [T06014] variants (eg, variants nos. 3, 11, 12) in normal and tumor-derived lung samples as determined by real-time PCR using primers of SEQ ID NO: 1529 2 is a histogram showing expression on two different scales. FIG. 56a shows the results at scales 0-1200. Figure 56b shows the results on scales 0-24. Relative to nucleolar protein 4 (NOL4) [T06014] variants (eg, variants nos. 3, 11, 12) in normal and tumor-derived lung samples as determined by real-time PCR using primers of SEQ ID NO: 1532 2 is a histogram showing expression on two different scales. Figure 57a shows the results on a scale of 0-2000. Figure 57b shows the results on scales 0-42. FIG. 16 is a histogram showing the relative expression of AA281370 variants (eg, variants nos. 0, 1, 4 and 5) in lung samples from normal and tumor as determined by real time PCR using the primers of SEQ ID NO: 1558. Histogram showing relative expression of sulfatase 1 (SULF1)-[Z21368] variants (eg, variants nos. 13 and 14) in lung samples from normal and tumor as determined by real time PCR using primers of SEQ ID NO: 1574 It is. SRY (sex-determining region Y) -box 2 (SOX2))-[HUMHMGBOX] variants in normal and tumor-derived lung samples, as determined by real-time PCR using primers of SEQ ID NO: 1594 (e.g. Is a histogram showing the relative expression of Pracophilin 1 (ectoderm dysplasia / epidermis varicella syndrome) (PKP-1)-[HSB6PR] mutant in normal and tumor-derived lung samples as determined by real-time PCR using primers of SEQ ID NO: 1600 (eg, FIG. 10 is a histogram showing relative expression of variant numbers 0, 5, and 6). The relative expression of transcripts detectable by SEQ ID NOs: 1480, 1517, 1529, 1532, 1558, 1574, 1600, 1616, 1619, 1622, 1625 in normal and tumor-derived lung samples, determined by real-time PCR It is a histogram to show. FIG. 6 shows an amino acid sequence alignment using NCBI BLAST default parameters showing the similarity between the AA281370 lung cancer biomarkers of the invention and the WD40 domain of various proteins involved in the MAPK signaling pathway. FIG. 63a: The amino acids 40-790 of the AA281370 polypeptide of SEQ ID NO: 99 are 75% homologous to the mouse Mapkbp1 protein (gi | 47124622). FIG. 6 shows an amino acid sequence alignment using NCBI BLAST default parameters showing the similarity between the AA281370 lung cancer biomarkers of the invention and the WD40 domain of various proteins involved in the MAPK signaling pathway. FIG. 63b: The amino acids 40 to 886 of the AA281370 polypeptide of SEQ ID NO: 99 are 70% homologous to the JNK binding protein JNKBP1 (gi | 34856717). A histogram showing overexpression of homo-Sapiens protease serine 21 (testisin) (PRSS21) AA 161 187 transcripts detectable by an amplicon as shown in sequence name AA161187seg25 in cancerous lung samples compared to normal samples is there. FIG. 16 is a histogram showing over expression of the tyrosine phosphatase receptor S-type (PTPRS) M62069 transcript, a protein detectable by an amplicon, shown in SEQ ID NO: M62069 segment 19 in cancerous lung samples compared to normal samples. FIG. 16 is a histogram showing over expression of the tyrosine phosphatase receptor S-type (PTPRS) M62069 transcript, a protein detectable by an amplicon, as set forth in SEQ ID NO: M62069 seg29 in cancerous lung samples compared to normal samples. FIG. 10 is a histogram showing the overexpression of the homo sapiens collagen type XI α1 (COL11A1) transcript as detected in the amplicon as shown in the sequence name HUMCA1X1Aseg55 in cancerous lung samples compared to normal samples. Histogram showing down-regulation of homo-Sapiens secreting leukocyte protease inhibitor (anti-leukoproteinase) (SLPI) Z25299 transcripts detectable by amplicon as shown in SEQ ID NO: Z 25 299 seg 23 in cancerous lung samples compared to normal samples It is. FIG. 16 is a histogram showing expression of the acid stable proteinase inhibitor Z25299 transcript, which is a secreted leukocyte protease inhibitor detectable by an amplicon, as set forth in the sequence name Z25299seg20 in different normal tissues. FIG. 16 is a histogram showing expression of the acid stable proteinase inhibitor Z25299 transcript, a secreted leukocyte protease inhibitor detectable by an amplicon, as set forth in the sequence name Z25299seg23 in different normal tissues. Overexpression of homo-sapiens matrix metalloproteinase 11 (stromelysin 3) (MMP11) (HSSTROL3) transcript detectable by amplicon as shown in the sequence name HSSTROL3seg20-2 in cancerous lung samples compared to normal samples It is a histogram to show. Overexpression of homo sapiens matrix metalloproteinase 11 (stromelysin 3) (MMP 11) (HSSTROL 3) transcript detectable by amplicon as shown in the sequence name HSSTROL3 junc 21-27 in cancerous lung samples compared to normal samples It is a histogram to show. FIG. 10 is a histogram showing the expression of R11723 transcripts detectable by amplicon as shown in the sequence name R11723junc11-28 in different normal tissues. The excess of homo-sapiens fibroblast growth factor receptor-like (like) 1 (FGFRL1) H53626 transcripts detectable by the amplicon shown in SEQ ID NO: H53626junc24-27F1R3 in cancerous lung samples compared to normal samples It is a histogram which shows expression. FIG. 6 is a histogram showing expression of homo-Sapiens fibroblast growth factor receptor-like 1 (FGFRL1) H53626 transcripts detectable by an amplicon, as set forth in SEQ ID NO: H53626 segment 25 in cancerous lung samples compared to normal samples . FIG. 16 is a histogram showing cancer versus cell line expression versus normal tissue expression for cluster H53626, showing overexpression in epithelial malignancies, a mixture of malignancies from different tissues, and myomas. FIG. 16 is a histogram showing the expression of homo-Sapiens fibroblast growth factor receptor-like 1 (FGFRL1) H53626 transcripts detectable by an amplicon as shown in the sequence name H53626seg25 in different normal tissues. FIG. 16 is a histogram showing the expression of homo-Sapiens fibroblast growth factor receptor-like 1 (FGFRL1) H53626 transcripts as indicated in the SEQ ID NO: H53626juncc24-27F1R3 in different normal tissues, detectable by an amplicon. PSEC R11723_PEA_1 T5 PCR product. Lane 1: PCR product, lane 2: Low DNA Mass Ladder MW marker (Invitrogen Cat # 10068-013). PSEC R11723_PEA_1 T5 PCR product sequence. Red-PSEC forward primer, blue-PSEC reverse complement sequence, highlighted sequence-PSEC variant R11723_PEA_1 T5 ORF. FIG. 5 shows PRSEC PCR products digested with NheI and HindIII. Lane 1-PRSET PCR product, lane 2-Fermentas GeneRuler 1 Kb DNA ladder no. SM0313. FIG. 6 shows a plasmid map of His PSEC T5 pRSETA. FIG. 7 shows the protein sequence of PSEC mutant R11723_PEA_1T5. Red-6 His tag, blue-PSEC. It is a figure which shows the DNA sequence of HisPSEC T5 pRSETA. Bold-HisPSEC T5 open reading frame, flanking DNA sequence verified by italics-sequence analysis. FIG. 5 shows Western blot analysis of recombinant HisPSEC mutant R11723_PEA_1 T5. Lane 1: molecular weight marker (ProSieve color, Cambrex, Cat # 50 550), lane 2: HisPSEC T5 pRSETA T0, lane 3: His HisPSEC T5 pRSETA T3, lane 4: His HisPSEC T5 pRSETA To. n, lane 5: pRSET empty vector T0 (negative control), lane 6: pRSET empty vector T3 (negative control), lane 7: pRSET empty vector To. n (negative control), lane 8: His positive control protein (HisTroponinT7 pRSETAT3).

Claims (26)

  An isolated polynucleotide comprising a polynucleotide having the sequence of R11723_PEA_1_T5.   The isolated polynucleotide of claim 1 comprising a node having the sequence of R11723_PEA_1_node_13.   An isolated polypeptide comprising a polypeptide having the sequence of R11723_PEA_1_P13.   A first amino acid sequence corresponding to amino acids 1 to 63 of Q96AC2 and corresponding to amino acids 1 to 63 of R11723_PEA_1_P13, MWVLGIAATFCCLFLLPGFALQQCYQCEEFELNDCSSPEFIVNCTVNVQDMCQKEVMEQSA and a sequence corresponding to amino acids 64 to 75 of R11723_PEA_1_P13 The chimeric polypeptide encoding R11723_PEA_1_P13, comprising a second amino acid sequence that is at least about 95% homologous to and wherein said first amino acid sequence and said second amino acid sequence are adjacent and in sequence order The isolate according to item 3.   5. An isolated polypeptide according to claim 4, comprising a tail of R11723_PEA_1_P13 comprising a polypeptide which is at least about 95% homologous to the sequence DTKRTNTLLFEMRHFAKQLTT in R11723_PEA_1_P13.   An isolated oligonucleotide according to claim 1, comprising the amplicon of SEQ ID NO: 1684.   A primer pair comprising an isolated oligonucleotide pair capable of amplifying the amplicon of claim 5.   7. The primer pair of claim 6, comprising the isolated oligonucleotide pair of SEQ ID NOS: 1682 and 1683.   An antibody capable of specifically binding to an epitope of the amino acid sequence according to claim 3.   9. The antibody of claim 8, wherein the amino acid sequence comprises the tail of claim 4.   9. The antibody according to claim 8, wherein said antibody can distinguish between a splice variant carrying said epitope and the corresponding known protein PSEC.   A kit for lung cancer detection which detects overexpression of the splice variant according to claim 1.   The kit of claim 11, wherein the kit comprises NAT based technology.   12. The kit of claim 11, wherein the kit further comprises at least one primer pair capable of selectively hybridizing to the nucleic acid sequence of claim 1.   12. The kit of claim 11, wherein the kit further comprises at least one oligonucleotide capable of selectively hybridizing to the nucleic acid sequence of claim 1.   A kit for detecting a lung cancer, comprising a kit for detecting overexpression of the splice variant according to claim 3, wherein the kit comprises the antibody according to claim 8.   13. The kit of claim 12, wherein the kit further comprises at least one reagent for performing an ELISA or a Western blot.   A method of detecting lung cancer comprising the step of detecting overexpression of the splice variant according to claim 1.   15. The method of claim 14, wherein the detection of overexpression is performed using NAT based technology.   A method for detecting lung cancer, comprising the step of detecting overexpression of the splice variant according to claim 3, wherein said detection of overexpression is carried out using an immunoassay.   17. The method of claim 16, wherein the immunoassay comprises the antibody of claim 8.   A biomarker capable of detecting lung cancer comprising the nucleic acid sequence of claim 1 or a fragment thereof or the amino acid sequence of claim 3 or a fragment thereof.   A method for screening lung cancer, comprising the step of detecting lung cancer cells with the biomarker according to claim 18.   A method for diagnosing lung cancer, comprising the step of detecting lung cancer cells with the biomarker according to claim 18.   A method of monitoring disease progression and / or therapeutic efficacy and / or lung cancer recurrence comprising detecting lung cancer cells with the biomarker according to claim 18.   A method for selecting a lung cancer treatment, comprising the steps of detecting lung cancer cells with the biomarker according to claim 18, and selecting a treatment by the detection.

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