US20020102542A1

US20020102542A1 - Polypeptide, cdna encoding the polypeptide, and use of the both

Info

Publication number: US20020102542A1
Application number: US09/529,063
Authority: US
Inventors: Daikichi Fukushima; Shiro Shibayama; Hideaki Tada
Original assignee: Ono Pharmaceutical Co Ltd
Current assignee: Ono Pharmaceutical Co Ltd
Priority date: 1997-10-07
Filing date: 1998-10-06
Publication date: 2002-08-01
Also published as: US7638281B2; EP1022286A1; KR100631766B1; KR20010015711A; US7189546B2; US20030165981A1; EP1375515A2; EP1627886A1; EP1375515A3; US20080009056A1; WO1999018126A1; EP1022286A4

Abstract

A new polypeptide prepared from human library by the SST method and a process for preparation of it; a cDNA encoding the polypeptide; a fragment selectively hybridizing with the sequence of the cDNA; a replication or expression plasmid containing the cDNA integrated thereinto; a host cell transformed with plasmid; an antibody against the polypeptide; and a pharmaceutical composition containing the polypeptide or the antibody.

Description

TECHNICAL FIELD

The present invention relates to novel polypeptides, a method for preparation of them, a cDNA encoding it, a vector containing it, a host cell transformed with the vector, an antibody against the peptide, and a pharmaceutical composition containing the polypeptide or the antibody.

TECHNICAL BACKGROUND

Until now, when a man skilled in the art intends to obtain a particular polypeptide or a cDNA encoding it, he generally utilizes methods by confirming an aimed biological activity in a tissue or in a cell medium, isolating and purifying the polypeptide and then cloning a gene or methods by “expression-cloning” with the guidance of the said biological activity. However, physiologically active polypeptides in living body have often many kinds of activities. Therefore, it happens increasingly that after cloning a gene, the isolated gene is found to be identical to that encoding a polypeptide already known. In addition, some factors could be generated in only a very slight amount and/or under specific conditions and it makes difficult to isolate and to purify the factor and to confirm its biological activity.

Recent rapid developments in techniques for constructing cDNAs and sequencing techniques have made it possible to quickly sequence a large amount of cDNAs. By utilizing these techniques, a process, which comprises constructing cDNAs library using various cells or tissues, cloning the cDNA at random, identifying the nucleotide sequences thereof, expressing novel polypeptides encoded by them, is now in progress. Although this process is advantageous in that a gene can be cloned and information regarding its nucleotide sequence can be obtained without any biochemical or genetic analysis, the target gene can be discovered thereby only accidentally in many cases.

The present inventors have studied cloning method to isolate genes encoding proliferation and/or differentiation factors functioning in hematopoietic systems and immune systems. Focusing their attention on the fact that most of the secretory proteins such as proliferation and/or differentiation factors (for example various cytokines) and membrane proteins such as receptors thereof (hereafter these proteins will be referred to generally as secretory proteins and the like) have sequences called signal peptides in the N-termini, the inventors have conducted extensive studies on a process for efficiently and selectively cloning a gene encoding for a signal peptide. Finally, we have successfully developed a screening method for the signal peptides (signal sequence trap (SST)) by using mammalian cells (See Japanese Patent Application No. Hei 6-13951). We also developed yeast SST method on the same concept. By the method based on the same conception using yeast, (yeast SST method), genes including sequence encoding signal peptide can be identified more easily and efficiently (See U.S. Pat. No. 5,536,637).

DISCLOSURE OF THE PRESENT INVENTION

The present inventors et al. have diligently performed certain investigation in order to isolate novel factors (polypeptides) useful for treatment, diagnosis and/or study, particularly, secretory proteins containing secretory signal and membrane protein.

From the result, the present inventors achieved to find novel secretory proteins and membrane proteins produced from cell lines and tissue, for example, human placenta, human adult brain tissue, cell lines derived from human brain tissue, human bone, cell line derived from human bone marrow, and endothelial cell line of vein derived from human umbilical cord and cDNAs encoding them, and then completed the present invention.

The present invention provides the cDNA sequences identified as clone ON056, ON034, OX003 which were isolated by the said yeast SST method using cDNA libraries prepared from human placenta tissue. Clone ON056, ON034, OX003 were full-length cDNA including full cDNA sequences encoding secretory proteins (Each protein is represented as ON056, ON034, OX003 protein, respectively).

It was indicated from the results of homology search for the public database of the nucleic acid sequences by using BLASTN and FASTA, and for the public database of the amino acid sequences by using BLASTX, BLASTP and FASTA, that there was no sequence identical to the polypeptide sequence and the nucleotide sequence of ON056, ON034, OX003 of the present invention. From the above, it was proved that polypeptides of the present invention were new secretary proteins.

The present invention provides the cDNA sequences identified as clone OA052, OC004, OM017, OM101, OM126, OM160, OMA016a, OMA016b, OMB130, OMB142, OVB100 which were isolated by the said yeast SST method using cDNA libraries prepared from human adult brain tissue and cell lines derived from human brain tissue (T98G, IMR-32, and CCF-STTG1). Clone OA052, OC004, OM017, OM101, OM126, OM160, OMA016a, OMA016b, OMB130, OMB142, OVB100003 were full-length cDNA including full cDNA sequences encoding secretory protein (Each protein is represented as OA052, OC004, OM017, OM101, OM126, OM160, OMA016a, OMA016b, OMB130, OMB142, OVB100 protein, respectively).

It was indicated from the results of homology search for the public database of the nucleic acid sequences by using BLASTN and FASTA, and for the public database of the amino acid sequences by using BLASTX, BLASTP and FASTA, that there was no sequence identical to the polypeptide sequence and the nucleotide sequence of OA052, OC004, OM017, OM101, OM126, OM160, OMA016a, OMA016b, OMB130, OMB142, OVB100 of the present invention. From these results, it was proved that polypeptides of the present invention were new secretary proteins.

The present invention provides the cDNA sequences identified as clone OAF062, OAF075, OAG119 which were isolated by the said yeast SST method using cDNA libraries prepared from human bone and bone marrow cell line (HAS303, LP101. Clone OAF062, OAF075, OAG119003 were full-length cDNA including full cDNA sequences encoding secretory protein (Each protein is represented as OAF062, OAF075, OAG119 protein, respectively).

It was indicated from the results of homology search for the public database of the nucleic acid sequences by using BLASTN and FASTA, and for the public database of the amino acid sequences by using BLASTX, BLASTP and FASTA, that there was no sequence identical to the polypeptide sequence and the nucleotide sequence of OAF062, OAF075, OAG119 of the present invention. From these results, it was proved that polypeptides of the present invention were new secretary proteins.

The present invention provides the cDNA sequences identified as clone OAH040, OAH058 which were isolated by the said yeast SST method using cDNA libraries prepared from epithelial cell line of human umbilical vein (HUV-EC-C). Clone OAH040, OAH058003 were full-length cDNA including full cDNA sequences encoding secretory protein (Each protein is represented as OAH040, OAH058 protein, respectively).

It was indicated from the results of homology search for the public database of the nucleic acid sequences by using BLASTN and FASTA, and for the public database of the amino acid sequences by using BLASTX, BLASTP and FASTA, that there was no sequence identical to the polypeptide sequence and the nucleotide sequence of OAH040, OAH058 of the present invention. From these results, it was proved that polypeptides of the present invention were new secretary proteins.

The present invention provides the cDNA sequences identified as clone OM011, OM028, OMB092, OMB108, OT007 which were isolated by the said yeast SST method using cDNA libraries prepared from human adult brain tissue and cell lines derived from human brain tissue (IMR-32). Clone OM011, OM028, OMB092, OMB108, OT007

membrane protein (Each protein is represented as OM011, OM028, OMB092, OMB108, OT007 protein, respectively).

It was indicated from the results of homology search for the public database of the nucleic acid sequences by using BLASTN and FASTA, and for the public database of the amino acid sequences by using BLASTX, BLASTP and FASTA, that there was no sequence identical to the polypeptide sequence and the nucleotide sequence of OM011, OM028, OMB092, OMB108, OT007 of the present invention. From these results, it was proved that polypeptides of the present invention were new secretary proteins.

The present invention provides the cDNA sequences identified as clone OAG051, OUB068 which were isolated by the said yeast SST method using cDNA libraries prepared from human bone and bone marrow cell line (LP101 and U-2OS). Clone OAG051, OUB068

membrane protein (Each protein is represented as OAG051, OUB068 protein, respectively).

It was indicated from the results of homology search for the public database of the nucleic acid sequences by using BLASTN and FASTA, and for the public database of the amino acid sequences by using BLASTX, BLASTP and FASTA, that there was no sequence identical to the polypeptide sequence and the nucleotide sequence of OAG051, OUB068 of the present invention. From these results, it was proved that polypeptides of the present invention were new secretary proteins.

That is to say, the present invention relates to

(1) a polypeptide comprising an amino acid sequence of SEQ ID NOS. 1, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40, 43, 46, 49, 52, 55, 58, 61, 64, 67, 70, 73, 76 or 79,

(2) a cDNA encoding the polypeptide described in (1),

(3) a cDNA comprising a nucleotide sequence of SEQ ID NOS. 2, 5, 8, 11, 14, 17, 20, 23, 26, 29, 32, 35, 38, 41, 44, 47, 50, 53, 56, 59, 62, 65, 68, 71, 74, 77 or 80, and

(4) a cDNA comprising a nucleotide sequence of SEQ ID NOS. 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78 or 81.

BRIEF DESCRIPTION OF THE DRAWING

FIG. 1 is a printed data of electrophoresis (SDS-PAGE). Each prepared fraction and the solubilized fraction obtained from insolble fraction by urea described in Example 1 were subjected to SDS-PAGE. The proteins on the gel were detected by image analyzer (BAS2000) as shown in the FIG. 1. The expression of ON056 in [0024] E. coli is shown at the arrowhead in the figure.

DETAILED DESCRIPTION OF THE PRESENT INVENTION

The present invention relates to a substantially purified form of the polypeptide comprising the amino acid sequence shown in SEQ ID NOS. 1, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40, 43, 46, 49, 52, 55, 58, 61, 64, 67, 70, 73, 76 or 79, homologue thereof, fragment thereof or homologue of the fragment. [0025]
Further, the present invention relates to cDNAs encoding the above peptides. More particularly the invention is provided cDNAs comprising nucleotide sequence shown in SEQ ID NOS. 2, 5, 8, 11, 14, 17, 20, 23, 26, 29, 32, 35, 38, 41, 44, 47, 50, 53, 56, 59, 62, 65, 68, 71, 74, 77, 80, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78 or 81, and cDNA containing a fragment which is selectively hybridizing to the cDNA comprising nucleotide sequence shown in SEQ ID NOS. 2, 5, 8, 11, 14, 17, 20, 23, 26, 29, 32, 35, 38, 41, 44, 47, 50, 53, 56, 59, 62, 65, 68, 71, 74, 77, 80, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78 or 81. A said cDNA capable for hybridizing to the cDNA includes the contemporary sequence of the above sequence. [0026]
A polypeptide comprising amino acid sequence shown in SEQ ID NOS. 1, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40, 43, 46, 49, 52, 55, 58, 61, 64, 67, 70, 73, 76 or 79 in substantially purified form will generally comprise the polypeptide in a preparation in which more than 90%, e.g. 95%, 98% or 99% of the polypeptide in the preparation is that of the SEQ ID NOS. 1, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40, 43, 46, 49, 52, 55, 58, 61, 64, 67, 70, 73, 76 or 79. [0027]
A homologue of polypeptide comprising amino acid sequence shown in SEQ ID NOS. 1, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40, 43, 46, 49, 52, 55, 58, 61, 64, 67, 70, 73, 76 or 79 will be generally at least 70%, preferably at least 80 or 90% and more preferably at least 95% homologous to the polypeptide comprising the said amino acid sequence over a region of at least 20, preferably at least 30, for instance 40, 60 or 100 more contiguous amino acids. Such a polypeptide homologue will be referred to a polypeptide of the present invention. [0028]
Generally, a fragment of polypeptide comprising amino acid sequence shown in SEQ ID NOS. 1, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40, 43, 46, 49, 52, 55, 58, 61, 64, 67, 70, 73, 76 or 79 or its homologues will be at least 10, preferably at least 15, for example 20, 25, 30, 40, 50 or 60 amino acids in length. [0029]
A cDNA capable of selectively hybridizing to the cDNA comprising nucleotide sequence shown in SEQ ID NOS. 2, 5, 8, 11, 14, 17, 20, 23, 26, 29, 32, 35, 38, 41, 44, 47, 50, 53, 56, 59, 62, 65, 68, 71, 74, 77, 80, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78 or 81 will be generally at least 70%, preferably at least 80 or 90% and more preferably at least 95% homologous to the cDNA comprising the said nucleotide sequence over a region of at least 20, preferably at least 30, for instance 40, 60 or 100 or more contiguous nucleotides. Such a cDNA will be referred to “a cDNA of the present invention”. [0030]
Fragments of the cDNA comprising nucleotide sequence shown in SEQ ID NOS. 2, 5, 8, 11, 14, 17, 20, 23, 26, 29, 32, 35, 38, 41, 44, 47, 50, 53, 56, 59, 62, 65, 68, 71, 74, 77, 80, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78 or 81 will be at least 10, preferably at least 15, for example 20, 25, 30 or 40 nucleotides in length, and will be also referred to “a cDNA of the present invention” as used herein. [0031]
A further embodiment of the present invention provides replication and expression vectors carrying cDNA of the present invention. The vectors may be, for example, plasmid, virus or phage vectors provided with an origin of replication, optionally a promoter for the expression of the said cDNA and optionally a regulator of the promoter. The vector may contain one or more selectable marker genes, for example ampicillin resistance gene. The vector may be used in vitro, for example of the production of RNA corresponding to the cDNA, or used to transfect a host cell. [0032]
A further embodiment of the present invention provides host cells transformed with the vectors for the replication and expression of the cDNA of the present invention, including the cDNA comprising nucleotide sequence shown in SEQ ID NOS. 2, 5, 8, 11, 14, 17, 20, 23, 26, 29, 32, 35, 38, 41, 44, 47, 50, 53, 56, 59, 62, 65, 68, 71, 74, 77, 80, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78 or 81 or the open reading frame thereof. The cells will be chosen to be compatible with the vector and may for example be bacterial, yeast, insect cells or mammalian cells. [0033]
A further embodiment of the present invention provides a method of producing a polypeptide which comprises culturing host cells of the present invention under conditions effective to express a polypeptide of the present invention. Preferably, in addition, such a method is carried out under conditions in which the polypeptide of the present invention is expressed and then produced from the host cells. [0034]
cDNA of the present invention may also be inserted into the vectors described above in an antisense orientation in order to prove for the production of antisense RNA. Such antisense RNA may be used in a method of controlling the levels of a polypeptide of the present invention in a cell. [0035]
The invention also provides monoclonal or polyclonal antibodies against a polypeptide of the present invention. The invention further provides a process for the production of monoclonal or polyclonal antibodies to the polypeptides of the present invention. Monoclonal antibodies may be prepared by common hybridoma technology using polypeptides of the present invention or fragments thereof, as an immunogen. Polyclonal antibodies may also be prepared by common means which comprise inoculating host animals, (for example a rat or a rabbit etc.), with polypeptides of the present invention and recovering immune serum. [0036]
The present invention also provides pharmaceutical compositions containing a polypeptide of the present invention, or an antibody thereof, in association with a pharmaceutically acceptable diluent and/or carrier. [0037]
The polypeptide of the present invention specified in (1) includes that which a part of their amino acid sequence is lacking (e.g., a polypeptide comprised of the only essential sequence for revealing a biological activity in an amino acid sequence shown in SEQ ID NO. 1), that which a part of their amino acid sequence is replaced by other amino acids (e.g., those replaced by an amino acid having a similar property) and that which other amino acids are added or inserted into a part of their amino acid sequence, as well as those comprising the amino acid sequence shown in SEQ ID NOS. 1, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40, 43, 46, 49, 52, 55, 58, 61, 64, 67, 70, 73, 76 or 79. [0038]
As known well, there are one to six kinds of codon as that encoding one amino acid (for example, one kind of codon for Methionine (Met), and six kinds of codon for Leucine (Leu) are known). Accordingly, the nucleotide sequence of cDNA can be changed in order to encode the polypeptide having the same amino acid sequence. [0039]
The cDNA of the present invention, specified in (2) includes a group of every nucleotide sequence encoding polypeptides (1) shown in SEQ ID NOS. 1, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40, 43, 46, 49, 52, 55, 58, 61, 64, 67, 70, 73, 76 or 79. There is a probability that yield of a polypeptide is improved by changing a nucleotide sequence. [0040]
The cDNA specified in (3) is the embodiment of the cDNA shown in (2), and indicate the sequence of natural form. [0041]
The cDNA shown in (4) indicates the sequence of the cDNA specified in (3) with natural non-translational region. [0042]
cDNA carrying nucleotide sequence shown in SEQ ID NOS. 3 is prepared by the following method: [0043]
Brief description of Yeast SST method (see U.S. Pat. No.5,536,637) is as follows. [0044]
Yeast such as [0045] Saccharomyces cerevisiae should secrete invertase into the medium in order to take sucrose or raffinose as a source of energy or carbon. (Invertase is an enzyme to cleave raffinose into sucrose and melibiose, sucrose into fructose and glucose.). It is known that many known mammalian signal sequence make yeast secrete its invertase. From these knowledge, SST method was developed as a screening method to find novel signal peptide which make it possible can to secrete yeast invertase from mammalian cDNA library. SST method uses yeast growth on raffinose medium as a marker. Non-secretory type invertase gene SUC2 (GENBANK Accession No. V 01311) lacking initiation codon ATG was inserted to yeast expression vector to prepare yeast SST vector pSUC2. In this expression vector, ADH promoter, ADH terminator (both were derived from MH5 plasmid (Gammerer, Methods in Enzymol. 101, 192-201, 1983)), 2m ori (as a yeast replication origin), TRP1 (as a yeast selective marker), ColE1 ori (as a E. coli replication origin) and ampicillin resistance gene (as a drug resistance marker) were inserted. Mammalian cDNA was inserted into the upstream of SUC2 gene to prepare yeast SST cDNA library. Yeast lacking secretory type invertase, was transformed with this library. If inserted mammalian cDNA encodes a signal peptide, yeast could survive in raffinose medium as a result of restoring secretion of invertase. Only to culture yeast colonies, prepare plasmids and determine the nucleotide sequence of the insert cDNAs, it is possible to identify novel signal peptide rapidly and easily.
Preparation of yeast SST cDNA library is as follows: [0046]
(1) mRNA is isolated from the targeted cells, double-strand synthesis is performed by using random primer with certain restriction enzyme (enzyme I) recognition site, [0047]
(2) obtained double-strand cDNA is ligated to adapter containing certain restriction endonuclease (enzyme II) recognition site, differ from enzyme I, digested with enzyme I and fractionated in a appropriate size, [0048]
(3) obtained cDNA fragment is inserted into yeast expression vector on the upstream region of invertase gene which signal peptide is deleted and the library was transformed. [0049]
Detailed description of each step is as follows: [0050]
(1) mRNA is isolated from mammalian organs and cell lines stimulate them with appropriate stimulator if necessary) by known methods (Molecular Cloning (Sambrook, J., Fritsch, E. F. and Maniatis, T, Cold Spring Harbor Laboratory Press, 1989) or Current Protocol in Molecular Biology (F. M. Ausubel et al, John Wiley & Sons, Inc.) if not remark especially). [0051]
TG98G (human glioblastoma cell line: ATCC No. CRL-1690), IMR-32 (human neuroblastoma cell line: ATCC No. CCL-127), U-2OS (human osteosarcoma cell line: ATCC No. HTB-96), CCF-STTG1 (human astrocytoma cell line: ATCC No. CRL-1718), HAS303 (human bone marrow stroma cell line: provide from Professor Keisuke Sotoyama, Dr. Makoto Aizawa of First Medicine, Tokyo Medical College; see J. Cell. Physiol., 148, 245-251, 1991 and Experimental Hematol., 22, 482-487, 1994), LP101 (human bone marrow stroma cell line: provide -from Professor Keisuke Sotoyama, Dr. Makoto Aizawa of First Medicine, Tokyo Medical College; see J. Cell. Physiol., 148, 245-251, 1991 and Experimental Hematol., 22, 482-487, 1994) and HUV-EC-C (endothelial cell of vein derived from human umbilical cord: ATCC No. CRL-1730) are chosen as a cell line. Human placenta and human adult brain are chosen as a tissue source. Double-strand cDNA synthesis using random primer is performed by known methods. [0052]
Any sites may be used as restriction endonuclease recognition site I which is linked to adapter and restriction endonuclease recognition site II which is used in step (2), if both sites are different each other. Preferably, XhoI is used as enzyme I and EcoRI as enzyme II. [0053]
In step (2), cDNA is created blunt-ends with T4 DNA polymerase, ligated enzyme II adapter and digested with enzyme I. Fragment cDNA is analyzed with agarose-gel electrophoresis (AGE) and is selected cDNA fraction ranging in size from 300 to 800 bp. As mentioned above, any enzyme may be used as enzyme II if it is not same the enzyme I. [0054]
In step (3), cDNA fragment obtained in step (2) is inserted into yeast expression vector on the upstream region of invertase gene which signal peptide is deleted. [0055] E. coli was transformed with the expression vector. Many vectors are known as yeast expression plasmid vector. For example, YEp24 is also functioned in E. coli. Preferably pSUC2 as described above is used.
Many host [0056] E. coli strains are known for transformation, preferably DH10B competent cell is used. Any known transformation method is available, preferably it is performed by electropolation method. Transformant is cultured by conventional methods to obtain cDNA library for yeast SST method.
However not every all of the clones do not contain cDNA fragment. Further all of the gene fragments do not encode unknown signal peptides. It is therefore necessary to screen a gene fragment encoding for an unknown signal peptide from the library. [0057]
Therefore, screening of fragments containing a sequence encoding an appropriate signal peptide is performed by transformation of the cDNA library into [0058] Saccharomyces cerevisiae (e.g. YT455 strain) which lack invertase (it may be prepared by known methods.). Transformation of yeast is performed by known methods, e.g. lithium acetate method. Transformant is cultured in a selective medium, then transferred to a medium containing raffinose as a carbon source. Survival colonies are selected and then prepared plasmid. Survival colonies on a raffinose-medium indicates that some signal peptide of secretory protein was inserted to this clone.
As for isolated positive clones, the nucleotide sequence is determined. As to a cDNA encodes unknown protein, full-length clone may be isolated by using cDNA fragment as a probe and then determined to obtain full-length nucleotide sequence. These manipulation is performed by known methods. [0059]
Once the nucleotide sequences shown in SEQ ID NO. 2, 5, 8, 11, 14, 17, 20, 23, 26, 29, 32, 35, 38, 41, 44, 47, 50, 53, 56, 59, 62, 65, 68, 71, 74, 77, 80, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78 or 81 are determined partially or preferably fully, it is possible to obtain DNA encode mammalian protein itself, homologue or subset. cDNA library or mRNA derived from mammals was screened by PCR with any synthesized oligonucleotide primers or by hybridization with any fragment as a probe. It is possible to obtain DNA encodes other mammalian homologue protein from other mammalian cDNA or genome library. [0060]
If a cDNA obtained above contains a nucleotide sequence of cDNA fragment obtained by SST (or consensus sequence thereof), it will be thought that the cDNA encodes signal peptide. So it is clear that the cDNA will be full-length or almost full. (All signal peptides exist at N-termini of a protein and are encoded at 5′-temini of open reading frame of cDNA.) [0061]
The confirmation may be carried out by Northern analysis with the said cDNA as a probe. It is thought that the cDNA is almost complete length, if length of the cDNA is almost the same length of the mRNA obtained in the hybridizing band. [0062]
Once the nucleotide sequences shown in SEQ ID NOS. 2, 5, 8, 11, 14, 17, 20, 23, 26, 29, 32, 35, 38, 41, 44, 47, 50, 53, 56, 59, 62, 65, 68, 71, 74, 77, 80, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78 or 81 are determined, DNAs of the invention are obtained by chemical synthesis, or by hybridization making use of nucleotide fragments which are chemically synthesized as a probe. Furthermore, DNAs of the invention are obtained in desired amount by transforming a vector that contains the DNA into a proper host, and culturing the transformant. [0063]
The polypeptides of the present invention may be prepared by: [0064]
(1) isolating and purifying from an organism or a cultured cell, [0065]
(2) chemically synthesizing, or [0066]
(3) using recombinant cDNA technology, [0067]
preferably, by the method described in (3) in an industrial production. [0068]
Examples of expression system (host-vector system) for producing a polypeptide by using recombinant cDNA technology are the expression systems of bacteria, yeast, insect cells and mammalian cells. [0069]
In the expression of the polypeptide, for example, in [0070] E. coli, the expression vector is prepared by adding the initiation codon (ATG) to 5′ end of a cDNA encoding mature peptide, connecting the cDNA thus obtained to the downstream of a proper promoter (e.g., trp promoter, lac promoter, λPL promoter, T7 promoter etc.), and then inserting it into a vector (e.g., pBR322, pUC18, pUC19 etc.) which functions in an E. coli strain.
Then, an [0071] E. coli strain (e.g., E. coli DH1 strain, E. coli JM109 strain, E. coli HB101 strain, etc.) which is transformed with the expression vector described above may be cultured in a appropriate medium to obtain the desired polypeptide. When a signal sequence of bacteria (e.g., signal sequence of pel B) is utilized, the desired polypeptide may be also released in periplasm. Furthermore, a fusion protein with other polypeptide may be also produced readily.
In the expression of the polypeptide, for example, in a mammalian cells, for example, the expression vector is prepared by inserting the cDNA encoding nucleotide shown in SEQ ID NOS. 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78 or 81 into the downstream of a proper promoter (e.g., SV40 promoter, LTR promoter, metallothionein promoter etc.) in a proper vector (e.g., retrovirus vector, papilloma virus vector, vaccinia virus vector, SV40 vector, etc.). A proper mammalian cell (e.g., monkey COS-7 cell, Chinese hamster CHO cell, mouse L cell etc.) is transformed with the expression vector thus obtained, and then the transformant is cultured in a proper medium to express the aimed secretory protein and membrane protein of the present invention by the following method. [0072]
In case of secretory protein as for the present invention, the aimed polypeptide was expressed in the supernatant of the cells. In addition, fusion protein may be prepared by conjugating cDNA fragment encoding the other polypeptide, for example, Fc portion of antibody. [0073]
On the other hand, in case of membrane protein as for the present invention, the aimed polypeptide was expressed on the cell membrane. A cDNA encoding the nucleotide sequence of SEQ ID NOS. 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78 or 81 with deletion of extracellular region was inserted into the said vector, transfected into the an adequate mammalian cells to secret the aimed soluble polypeptide in the culture medium. In addition, fusion protein may be prepared by conjugating cDNA fragment encoding the said mutant with deletion of extracellular region and other polypeptide, for example, Fc portion of antibody. [0074]
The polypeptide available by the way described above can be isolated and purified by conventional biochemical method. [0075]

INDUSTRIAL APPLICABILITY

It is considered that the polypeptide of the present invention and a cDNA which encodes the polypeptide will show one or more of the effects or biological activities (including those which relates to the assays cited below) The effects or biological activities described in relation to the polypeptide of the present invention are provided by administration or use of the polypeptide or by administration or use of a cDNA molecule which encodes the polypeptide (e.g., vector suitable for gene therapy or cDNA introduction). [0076]
Cytokine Activity and Cell Proliferation/Differentiation Activity [0077]
The protein of the present invention may exhibit cytokine, cell proliferation (either inducing or inhibiting) or cell differentiation (either inducing or inhibiting) activity or may induce production of other cytokines in certain cell populations. Many protein factors discovered to date, including all known cytokines, have exhibited activity in one or more factor dependent cell proliferation assays, and hence the assays serve as a convenient confirmation of cytokine activity. The activity of a polypeptide of the present invention is evidenced by any one of a number of routine factor dependent cell proliferation assays for cell lines. [0078]
Immune Stimulating/Suppressing Activity [0079]
The protein of the present invention may also exhibit immune stimulating or immune suppressing activity. The protein of the present invention may be useful in the treatment of various immune deficiencies and disorders (including severe combined immunodeficiency (SCID)), e.g., in regulating (up or down) growth and proliferation of T and/or B lymphocytes, as well as effecting the cytolytic activity of NK cells and other cell populations. These immune deficiencies may be genetic or be caused by viral infection such as HIV as well as bacterial or fungal infections, or may result from autoimmune disorders. More specifically, infectious diseases causes by viral, bacterial, fungal or other infection may be treatable using the polypeptide of the present invention, including infections by HIV, hepatitis viruses, herpes viruses, mycobacteria, leshmania, malaria and various fungal infections such as candida. Of course, in this regard, the protein of the present invention may also be useful where a boost to the immune system generally would be indicated, i.e., in the treatment of cancer. [0080]
The protein of the present invention may be useful in the treatment of allergic reactions and conditions, such as asthma or other respiratory problems. The protein of the present invention may also be useful in the treatment of the other conditions required to suppress the immuno system (for example, asthma or respiratory disease.) [0081]
The protein of the present invention may also suppress chronic or acute inflammation, such as, for example, that associated with infection such as septic shock or systemic inflammatory response syndrome (SIRS), inflammatory bowel disease, Crohn's disease or resulting from over production of cytokines such as TNF or IL-I wherein the effect was demonstrated by IL- 11. [0082]
Hematopoiesis Regulating Activity [0083]
The protein of the present invention may be useful in regulation of hematopoiesis and, consequently, in the treatment of myeloid or lymphoid cell deficiencies. Even marginal biological activity in support of colony forming cells or of factor-dependent cell lines indicates involvement in regulating hematopoiesis. The said biological activities are concerned with the following all or some example(s). e.g. in supporting the growth and proliferation of erythroid progenitor cells alone or in combination with other cytokines, thereby indicating utility, for example, in treating various anemia or for use in conjunction with irradiation/chemotherapy to stimulate the production of erythroid precursors and/or erythroid cells; in supporting the growth and proliferation of myeloid cells such as granulocytes and monocytes/macrophages (i.e., traditional CSF activity) useful, for example, in conjunction with chemotherapy to prevent or treat consequent myelo-suppression; in supporting the growth and proliferation of megakaryocytes and consequently of platelets thereby allowing prevention or treatment of various platelet disorders such as thrombocytopenia, and generally for use in place of or complimentary to platelet transfusions; and/or in supporting the growth and proliferation of hematopoietic stem cells which are capable of maturing to any and all of the above-mentioned hematopoietic cells and therefore find therapeutic utility in various stem cell disorders (such as those usually treated with transplantation, including, without limitation, aplastic anemia and paroxysmal nocturnal hemoglobinuria), as well as in repopulating the stem cell compartment post irradiation/chemotherapy, either in-vitro or ex-vivo (i.e. in conjunction with bone marrow transplantation) as normal cells or genetically manipulated for gene therapy. [0084]
The activity of the protein of the present invention may, among other means, be measured by the following methods: [0085]
Tissue Generation/Regeneration Activity [0086]
The protein of the present invention also may have utility in compositions used for bone, cartilage, tendon, Ligament and/or nerve tissue growth or regeneration, as well as for wound healing and tissue repair, and in the treatment of bums, incisions and ulcers. [0087]
The protein of the present invention, which induces cartilage and/or bone growth in circumstances where bone is not normally formed, may be applied to the healing of bone fractures and cartilage damage or defects in humans and other animals. Such a preparation employing the protein of the present invention may have prophylactic use in closed as well as open fracture reduction and also in the improved fixation of artificial joints. De novo bone formation induced by an osteogenic agent contributes to the repair of congenital, trauma induced, or oncologic resection induced craniofacial defects, and also is useful in cosmetic plastic surgery. [0088]
The protein of the present invention may also be used in the treatment of periodontal disease, and in other tooth repair processes. Such agents may provide an environment to attract bone-forming cells, stimulate growth of bone-forming cells or induce differentiation of progenitors of bone-forming cells. The protein of the present invention may also be useful in the treatment of osteoporosis or osteoarthritis, such as through stimulation of bone and/or cartilage repair or by blocking inflammation or processes of tissue destruction (collagenase activity, osteoclast activity, etc.) mediated by inflammatory processes. [0089]
Another category of tissue regeneration activity that may be attributable to the protein of the present invention is tendon/ligament formation. The protein of the present invention, which induces tendon/ligament-like tissue or other tissue formation in circumstances where such tissue is not normally formed, may be applied to the healing of tendon or ligament tears, deformities and other tendon or ligament defects in humans and other animals. Such a preparation employing the protein inducing a tendon/Ligament-like tissue may have prophylactic use in preventing damage to tendon or ligament tissue, as well as use in the improved fixation of tendon or ligament to bone or other tissues, and in repairing defects to tendon or ligament tissue. De novo tendon/ligament-like tissue formation induced by a composition of the present invention contributes to the repair of congenital, trauma induced, or other tendon or ligament defects of other origin, and is also useful in cosmetic plastic surgery for attachment or repair of tendons or ligaments. The compositions of the present invention may provide an environment to attract tendon- or ligament-forming cells, stimulate growth of tendon- or ligament-forming cells, induce differentiation of progenitors of tendon- or ligament-forming cells, or induce growth of tendon Ligament cells or progenitors ex vivo for return in vivo to effect tissue repair. The compositions of the present invention may also be useful in the treatment of tendinitis, Carpal tunnel syndrome and other tendon or ligament defects. The compositions may also include an appropriate matrix and/or sequestering agent as a carrier as is well known in the art. [0090]
The protein of the present invention may also be useful for proliferation of neural cells and for regeneration of nerve and brain tissue. i.e. for the treatment of central and peripheral nervous system diseases and neuropathies. as well as mechanical and traumatic disorders, which involve degeneration, death or trauma to neural cells or nerve tissue. More specifically, the protein of the present invention may be used in the treatment of diseases of the peripheral nervous system, such as peripheral nerve injuries, peripheral neuropathy and localized neuropathies, and central nervous system diseases, such as Alzheimer's, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and Shy-Drager syndrome. Further conditions which may be treated in accordance with the invention include mechanical and traumatic disorders, such as spinal cord disorders, head trauma and cerebrovascular diseases such as stroke. Peripheral neuropathies resulting from chemotherapy or other medical therapies may also be treatable using the polypeptide of the present invention. [0091]
It is expected that the protein of the present invention may also exhibit activity for generation of other tissues, such as organs (including, for example, pancreas, liver, intestine, kidney, skin, endothelium), muscle (smooth, skeletal or cardiac) and vascular (including vascular endothelium) tissue, or for promoting the proliferation of cells comprising such tissues. Part of the desired effects may be by inhibition of fibrotic scarring to allow normal tissue to regenerate. [0092]
The protein of the present invention may also be useful for gut protection or regeneration and treatment of lung or liver fibrosis, reperfusion injury in various tissues, and conditions resulting from systemic cytokine damage. [0093]
Activin/Inhibin Activity [0094]
The protein of the present invention may also exhibit activin- or inhibin-related activities. Inhibins are characterized by their ability to inhibit the release of follicle stimulating hormone (FSH), while activins are characterized by their ability to stimulate the release of follicle stimulating hormone (FSH). Thus, the protein of the present invention alone or in heterodimers with a member of the inhibin *a family, may be useful as a contraceptive based on the ability of inhibins to decrease fertility in female mammals and decrease spermatogenesis in male mammals. Administration of sufficient amounts of other inhibins can induce infertility in these mammals. [0095]
Alternatively, the protein of the present invention, as a homodimer or as a heterodimer with other protein subunits of the inhibin-*b group, may be useful as a fertility inducing therapeutic, based upon the ability of activin molecules in stimulating FSH release from cells of the anterior pituitary (See U.S. Pat. No. 4,798,885). The protein of the present invention may also be useful for advancement of the onset of fertility in sexually immature mammals, so as to increase the lifetime reproductive performance of domestic animals such as cows, sheep and pigs. [0096]
Chemotactic/Chemokinetic Activity [0097]
The protein of the present invention may have chemotactic or chemokinetic activity e.g., functioning as a chemokine, for mammalian cells, including, for example, monocytes, neutrophils, T-cells, mast cells, eosinophils and/or endothelial cells. Chemotactic and chemokinetic proteins can be used to mobilize or attract a desired cell population to a desired site of action. Chemotactic or chemokinetic proteins provide particular advantages in treatment of wounds and other trauma to tissues, as well as in treatment of localized infections. For example, attraction of lymphocytes, monocytes or neutrophils to tumors or sites of infection may result in improved immune responses against the tumor or infecting agent. [0098]
If a protein or peptide can stimulate, directly or indirectly, the directed orientation or movement of such cell population, it has chemotactic activity for a particular cell population. Preferably, the protein or peptide has the ability to directly stimulate directed movement of cells. Whether a particular protein has chemotactic activity for a population of cells can be readily determined by employing such protein or peptide in any known assay for cell chemotaxis. [0099]

Hemostatic and Thrombolytic Activity

The protein of the present invention may also exhibit hemostatic or thrombolyic activity. As a result, such a protein is expected to be useful in treatment of various coagulation disorders (including hereditary disorders, such as hemophilias) or to enhance coagulation and other hemostatic events in treating wounds resulting from trauma, surgery or other causes. A protein of the present invention may also be useful for dissolving or inhibiting formation of thromboses and for treatment and prevention of conditions resulting therefrom such as, for example, infarction or stroke. [0100]
Receptor/Ligand Activity [0101]
The protein of the present invention may also demonstrate activity as receptors, receptor ligands or inhibitors or agonists of receptor/ligand interactions. Examples of such receptors and ligands include, without limitation, cytokine receptors and their ligands, receptor kinases and their ligands, receptor phosphatases and their ligands, receptors involved in cell-cell interactions and their ligands (including cellular adhesion molecules such as Selectins, Integrins and their ligands) and receptor/ligand pairs involved in antigen presentation, antigen recognition and development of cellular and humoral immune responses. Receptors and ligands are also useful for screening of potential peptide or small molecule inhibitors of the relevant receptor/ligand interaction. The protein of the present invention (including, without limitation, fragments of receptors and ligands) may themselves be useful as inhibitors of receptor/ligand interactions. [0102]
Other Activity [0103]
The protein of the present invention may also exhibit one or more of the following additional activities or effects: inhibiting growth of or killing the infecting agents including bacteria, viruses, fungi and other parasites; effecting (suppressing or enhancing) body characteristics including height, weight, hair color, eye color, skin, other tissue pigmentation, or organ or body part size or shape such as, for example, breast augmentation or diminution etc.; effecting elimination of dietary fat, protein, carbohydrate; effecting behavioral characteristics including appetite, libido, stress, cognition (including cognitive disorders), depression and violent behaviors; providing analgesic effects or other pain reducing effects; promoting differentiation and growth of embryonic stem cells in lineages other than hematopoietic lineages; in the case of enzymes, correcting deficiencies of the enzyme and treating deficiency-related diseases. [0104]
The protein with above activities, is suspected to have following functions by itself or interaction with its ligands or receptors or association with other molecules. For example, proliferation or cell death of B cells, T cells and/or mast cells; specific induction by promotion of class switch of immunoglobulin genes; differentiation of B cells to antibody-forming cells; proliferation, differentiation, or cell death of precursors of granulocytes; proliferation, differentiation, or cell death of precursors of monocytes-macrophages; proliferation, of up regulation or cell death of neutrophils, monocytes-macrophages, eosinophils and/or basophils; proliferation, or cell death of precursors of megakaryocytes; proliferation, differentiation, or cell death of precursors of neutrophils; proliferation, differentiation, or cell death of precursors of T cells and B cells; promotion of production of erythrocytes; sustainment of proliferation of erythrocytes, neutrophils, eosinophils, basophils, monocytes-macrophages, mast cells, precursors of megakaryocyte; promotion of migration of neutrophils, monocytes-macrophages, B cells and/or T cells; proliferation or cell death of thymocytes; suppression of differentiation of adipocytes; proliferation or cell death of natural killer cells; proliferation or cell death of hematopoietic stem cells; suppression of proliferation of stem cells and each hematopoietic precursor cells; promotion of differentiation from mesenchymal stem cells to osteoblasts or chondrocytes, proliferation or cell death of mesenchymal stem cells, osteoblasts or chondrocytes and promotion of bone absorption by activation of osteoclasts and promotion of differentiation from monocytes to osteoclasts. [0105]
The polypeptide of the present invention is also suspected to function to nervous system, so expected to have functions below; differentiation to kinds of neurotransmitter-responsive neurons, survival or cell death of these cells; promotion of proliferation or cell death of glial cells; spread of neural dendrites; survival or cell death of gangriocytes; proliferation, promotion of differentiation, or cell death of astrocytes; proliferation, survival or cell death of peripheral neurons; proliferation or cell death of Schwann cells; proliferation, survival or cell death of motoneurons. [0106]
Furthermore, in the process of development of early embryonic, the polypeptide of the present invention is expected to promote or inhibit the organogenesis of epidermis, brain, backbone, and nervous system by induction of, ectoderm, that of notochord connective tissues (bone, muscle, tendon), hemocytes, heart, kidney, and genital organs by induction of mesoderm, and that of digestive apparatus (stomach, intestine, liver, pancreas), respiratory apparatus (lung, trachea) by induction of endoderm. In adult, also, this polypeptide is thought to proliferate or inhibit the above organs. [0107]
Therefore, the polypeptide of the present invention itself is expected to be used as an agent for the prevention or treatment of disease of progression or suppression of immune, nervous, or bone metabolic function, hypoplasia or overgrowth of hematopoietic cells: for example, inflammatory disease (rheumatism, ulcerative colitis, etc.), decrease of hematopoietic stem cells after bone marrow transplantation, decrease of leukocytes, platelets, B-cells, or T-cells after radiation exposure or chemotherapeutic dosage against cancer or leukemia, anemia, infectious disease, cancer, leukemia, AIDS, bone metabolic disease (osteoporosis etc.), various degenerative disease (Alzheimer's disease, multiple sclerosis, etc.), or nervous lesion. [0108]
In addition, since the polypeptide of the present invention is thought to induce the differentiation or growth of organs derived from ectoderm, mesoderm, and endoderm, this polypeptide is expected to be an agent for tissue repair (epidermis, bone, muscle, tendon, heart, kidney, stomach, intestine, liver, pancreas, lung, and trachea, etc.). [0109]
By using polyclonal or monoclonal antibodies against the polypeptide of the present invention, quantitation of the said polypeptide in the body can be performed. It can be used in the study of relationship between this polypeptide and disease or diagnosis of disease, and so on. Polyclonal and monoclonal antibodies can be prepared using this polypeptide or its fragment as an antigen by conventional methods. [0110]
Identification, purification or molecular cloning of known or unknown proteins which bind the polypeptide of the present invention (preferably polypeptide of extracellular domain) can be performed using the polypeptide of the present invention by, for example, preparation of the affinity-column. [0111]
Identification of the downstream signal transmission molecules which interact with the polypeptide of the present invention in cytoplasma and molecular cloning of the gene can be performed by west-western method using the polypeptide of the present invention (preferably polypeptide of transmembrane region or intracellular domain), or by yeast two-hybrid system using the cDNA (preferably cDNA encoding transmembrane region or cytoplasmic domain of the polypeptide). [0112]
Agonists/antagonists of this receptor polypeptide and inhibitors between receptor and signal transduction molecules can be screened using the polypeptide of the present invention. [0113]
cDNAs of the present invention are useful not only the important and essential template for the production of the polypeptide of the present invention which is expected to be largely useful, but also be useful for diagnosis or therapy (for example, treatment of gene lacking, treatment to stop the expression of the polypeptide by antisense cDNA (mRNA)). Genomic cDNA may be isolated with the cDNA of the present invention, as a probe. As the same manner, a human gene encoding which can be highly homologous to the cDNA of the present invention, that is, which encodes a polypeptide highly homologous to the polypeptide of the present invention and a gene of animals excluding mouse which can be highly homologous to the cDNA of the present invention, also may be isolated. [0114]
Application to Medicaments [0115]
The polypeptide of the present invention or the antibody specific for the polypeptide of the present invention is administered systemically or topically and in general orally or parenterally, preferably parenterally, intravenously and intraventricularly, for preventing or treating the said diseases. [0116]
The doses to be administered depend upon age, body weight, symptom, desired therapeutic effect, route of administration, and duration of the treatment etc. In human adults, one dose per person is generally between 100 μg and 100 mg, by oral administration, up to several times per day, and between 10 μg and 100 mg, by parental administration up to several times per day. [0117]
As mentioned above, the doses to be used depend upon various conditions. Therefore, there are cases in which doses lower than or greater than the ranges specified above may be used. [0118]
The compounds of the present invention, may be administered as solid compositions, liquid compositions or other compositions for oral administration, as injections, liniments or suppositories etc. for parental administration. [0119]
Solid compositions for oral administration include compressed tablets, pills, capsules, dispersible powders, and granules. Capsules include soft or hard capsules. [0120]
In such compositions, one or more of the active compound(s) is or are admixed with at least one inert diluent (such as lactose, mannitol, glucose, hydroxypropyl cellulose, microcrystalline cellulose, starch, polyvinylpyrrolidone, magnesium metasilicate aluminate, etc.). The compositions may also comprise, as is normal practice, additional substances other than inert diluents: e.g. lubricating agents (such as magnesium stearate etc.), disintegrating agents (such as cellulose calcium glycolate, etc.), stabilizing agents (such as human serum albumin, lactose etc.), and assisting agents for dissolving (such as arginine, asparaginic acid etc.). [0121]
The tablets or pills may, if desired, be coated with a film of gastric or enteric materials (such as sugar, gelatin, hydroxypropyl cellulose or hydroxypropylmethyl cellulose phthalate, etc.), or be coated with more than two films. And then, coating may include containment within capsules of absorbable materials such as gelatin. [0122]
Liquid compositions for oral administration include pharmaceutically-acceptable emulsions, solutions, syrups and elixirs. In such compositions, one or more of the active compound(s) is or are contained in inert diluent(s) commonly used (purified water, ethanol etc.). Besides inert diluents, such compositions may also comprise adjuvants (such as wetting agents, suspending agents, etc.), sweetening agents, flavoring agents, perfuming agents, and preserving agents. [0123]
Other compositions for oral administration include spray compositions which may be prepared by known methods and which comprise one or more of the active compound(s). Spray compositions may comprise additional substances other than inert diluents: e.g. stabilizing agents (sodium sulfite etc.), isotonic buffer (sodium chloride, sodium citrate, citric acid, etc.). For preparation of such spray compositions, for example, the method described in the U.S. Pat. No. 2,868,691 or 3,095,355 (herein incorporated in their entireties by reference) may be used. [0124]
Injections for parental administration include sterile aqueous or non-aqueous solutions, suspensions and emulsions. In such compositions, one or more active compound(s) is or are admixed with at least one inert aqueous diluent(s) (distilled water for injection, physiological salt solution, etc.) or inert non-aqueous diluents(s)(propylene glycol, polyethylene glycol, olive oil, ethanol, POLYSOLBATE 80 (Trade mark) etc.). [0125]
Injections may comprise additional compound other than inert diluents: e.g. preserving agents, wetting agents, emulsifying agents, dispersing agents, stabilizing agent (such as human serum albumin, lactose, etc.), and assisting agents such as assisting agents for dissolving (arginine, asparaginic acid, etc.). [0126]

BEST MODE CARRYING OUT THE INVENTION

The invention is illustrated by the following examples, but not limit the invention. [0127]

Example 1: Clone ON056

(1) Preparation of Poly(A)[0128] ⁺RNA
Total RNA was prepared from human placenta tissue by TRIzol reagent (Trade Mark, marketed by GIBCO BRL Co.). Poly(A)[0129] ⁺RNA was purified from the total RNA by mRNA Purification Kit (Trade name, marketed by Pharmacia Co.).
(2) Preparation of Yeast SST cDNA Library [0130]
Double strand cDNA was synthesized by Super Script Plasmid System for cDNA Synthesis and Plasmid Cloning (Trade name, marketed by GIBCO BRL Co.) with above poly(A)[0131] ⁺RNA as template and random 9mer as primer which was containing XhoI site:
5′-CGA TTG AAT TCT AGA CCT GCC TCG AGN NNN NNN NN-3′ (SEQ ID NO. 82).
cDNA was ligated EcoRI adapter by DNA ligation kit ver. 2 (Trade name, marketed by Takara Shuzo Co.; this kit was used in all ligating steps hereafter.) and digested by XhoI. cDNAs were separated by agarose-gel electrophoresis. 300˜800 bp cDNAs were isolated and were ligated to EcoRI/NotI site of pSUC2 (see U.S. Pat. No. 5,536,637). [0132] E. coli DH10B strains were transformed by pSUC2 with electropolation to obtain yeast SST cDNA library.
(3) Screening by SST Method and Determination of Nucleotide Sequence of SST Positive Clone [0133]
Plasmids of the said cDNA library were prepared. Yeast YTK12 strains were transformed by the plasmids with lithium acetate method (Current Protocols In Molecular Biology 13.7.1). The transformed yeast were plated on triptphan-free medium (CMD-Trp medium) for selection. The plate was incubated for 48 hour at 30° C. Replica of the colony (transformant) which was obtained by Accutran Replica Plater (Trade name, marketed by Schleicher & Schuell) were placed onto YPR plate containing raffinose for carbon source, and the plate was incubated for 14 days at 30° C. After 3 days, each colony appeared was streaked on YPR plate again. The plates were incubated for 48 hours at 30° C. Single colony was inoculated to YPD medium and was incubated for 48 hours at 30° C. Then plasmids were prepared. Insert cDNA was amplified by PCR with two kind primers which exist end side of cloning site on pSUC2 (sense strand primers were biotinylated). Biotinylated single strand of cDNAs were purified with Dynabeads (Trade name, marketed by DYNAL Co.) and the nucleotide sequences were determined. Sequencing was performed by Dye Terminator Cycle Sequencing Ready Reaction with DNA Sequencing kit (Trade name, marketed by Applied Biosystems Inc.) and sequence was determined by DNA sequencer 373 (Applied Biosystems Inc.) (All sequencing hereafter was carried out with this method.). [0134]
We tried to carry out cloning of full-length cDNA which was proved to be new one according to the homology search for the obtained nucleotide sequences and deduced amino acid sequences in data base. We also confirmed that each cDNA contains signal peptide in view of function and structure, by comparison with known peptide which has signal peptide and deduced amino acid sequence. [0135]
(4) Cloning of a Full-length cDNA and Determination of Nucleotide Sequence [0136]
A full-length cDNA was cloned using GENETRAPPER cDNA Positive Selection System (marketed by GIBCO BRL Co.). First, dT-primed cDNA library was prepared from poly (A)[0137] ⁺RNA in human placenta tissue using pSPORT1 plasmid (marketed by GIBCO BRL Co.), as a vector, by Super Script Plasmid System for cDNA Synthesis and Plasmid Cloning. Next, after preparing biotinylated primer ON056-F1 (27mer):
5′ biotin-AACATGAATCTTTCGCTCGTCCTGGCT-3′ (SEQ ID NO. 83)
based on the information of nucleotide sequence obtained by SST, plasmid hybridized specifically with the biotinylated primer were recovered from the cDNA library according to the method of Gene Trapper Kit and then transfected into [0138] E. coli DH10B. Colony hybridization with ON056 SST cDNA which was labeled with ³²P-dCTP, as a probe, was performed by using Random Primer DNA Labeling kit (Trade name, marketed by Takara Shuzo Co.) according to known method to isolate the positive clone and to prepare the plasmid. Nucleotide sequences of 5′-end were determined, and the existence of nucleotide sequence ON056 SST cDNA was confirmed. Nucleotide sequence of full-length ON056 SST cDNA was determined and then sequence shown in SEQ ID NO. 3 was obtained. An open reading frame was determined and deduced amino acid sequence and nucleotide sequence shown in SEQ ID NOS. 1 and 2, respectively, were obtained.
It was indicated from the results of homology search for the public database of the nucleic acid sequences by using BLASTN and FASTA, and for the public database of the amino acid sequences by using BLASTX, BLASTP and FASTA, that there was no sequence identical to the polypeptide sequence and the nucleotide sequence of ON056 of the present invention. From these results, it was proved that polypeptide of the present invention was new secretary protein. [0139]
However, the search using BLASTX, BLASTP and FASTA revealed a significant homology between clone ON056 (region of 1st˜334th amino acid in SEQ ID NO. 1) and Human Cathepsin L (Swiss Prot Accession P07711) (region of 1st˜334th amino acid) or between clone ON056 (region of 22nd˜334th amino acid in SEQ ID NO. 1) and Human Cathepsin K (Swiss Prot Accession P43235) (region of 19th˜329th amino acid). Based on these homologies, clone ON0566 and Human Cathepsin L family were expected to share at least some activity. [0140]
(5) Expression of Protein Using [0141] E. coli
The coding region cDNA fragments without sequence encoding signal peptide were amplified by PCR and inserted into the downstream of initiation codon ATG in pET expression vector (marketed by Novagen Co.) for [0142] E. coli inframe to construct the plasmid for expression. The obtained plasmids were transfected into E. coli BL21 (DE3) and the transformant was cultured with IPTG to induce the expression of protein. The obtained E. coli was harvested and lysed with ultra-sonication or detergent. The insoluble fraction was solubilized with urea and subjected to SDS-PAGE. The expression of ON056 protein was confirmed by Coomassie staining (arrow in FIG. 1).
(6) Expression of the Protein Using Mammalian Cell [0143]
Thus obtained full-length cDNA was conjugated into XhoI (or EcoRI)-NotI site of the pED6 expression vector of mammalian cells (See Kaufman et al., Nucleic Acids Res. 19, 4485-4490 (1991)) to construct plasmid to express the secretory protein or membrane protein. The obtained plasmids were transfected into Cos 7 cells using Lypofectine (Trade name, marketed by GIBCO BRL Co.). After 24 hours, the transfection mixture was removed. The cells were cultured in the Met and Cys-free medium with [0144] ³⁵S-labeled Met and ³⁵S-labeled Cys for 5 hours. The supernatants were harvested and 10-fold concentrated with Centricon-10 (Trade name, marketed by Amicon Co.). The samples were separated on SDS-PAGE gels. After drying the acrylamidogel, the expression of ³⁵S-labeled protein was detected using BAS2000 (marketed by Fuji Film Co.).

Example 2: Clone ON034

In Example relating to clone ON034 of the present invention, the same procedure as in Example of ON056 was used except for the following points. [0145]
(1) Preparation of Poly(A)[0146] ⁺RNA
Total RNA was prepared from human placenta tissue by TRIzol reagent. Poly(A)[0147] ⁺RNA was purified from the total RNA by mRNA Purification Kit.
(2) Cloning of a Full-length cDNA and Determination of Nucleotide Sequence [0148]
A full-length cDNA was cloned using GENETRAPPER cDNA Positive Selection System. First, dT-primed cDNA library was prepared from poly (A)+RNA in human placenta tissue using pSPORT1 plasmid, as a vector, by Super Script Plasmid System for cDNA Synthesis and Plasmid Cloning. Next, after preparing biotinylated primer ON034-F1 (28mer): [0149]
5′biotin-TGAAGCCCATCACTACATCGCCATTACG-3′ (SEQ ID NO.: 84)
based on the information of nucleotide sequence obtained by SST, plasmid hybridized specifically with the biotinylated primer were recovered from the cDNA library according to the method of Gene Trapper Kit and then transfected into [0150] E. coli DH10B. Colony hybridization with ON034 SST cDNA which was labeled with 32P-dCTP, as a probe, was performed by using Random Primer DNA Labeling kit according to known method to isolate the positive clone and to prepare the plasmid. Nucleotide sequence of full-length ON034 SST cDNA was determined by the same procedure as ON056 and then sequence shown in SEQ ID NO. 6 was obtained. An open reading frame was determined and deduced amino acid sequence and nucleotide sequence shown in SEQ ID NOS. 4 and 5, respectively, were obtained.
It was indicated from the results of homology search for the public database of the nucleic acid sequences by using BLASTN and FASTA, and for the public database of the amino acid sequences by using BLASTX, BLASTP and FASTA, that there was no sequence identical to the polypeptide sequence and the nucleotide sequence of ON034 of the present invention. From these results, it was proved that polypeptide of the present invention was new secretary protein. [0151]

Example 3: Clone OX003

In Example relating to clone OX003 of the present invention, the same procedure as in Example of ON056 was used except for the following points. [0152]
(1) Preparation of Poly(A)[0153] ⁺RNA
Total RNA was prepared from human placenta tissue by TRIzol reagent. Poly(A)[0154] ⁺RNA was purified from the total RNA by mRNA Purification Kit.
(2) Cloning of a Full-length cDNA and Determination of Nucleotide Sequence [0155]
A full-length cDNA was cloned using Marathon cDNA Amplification Kit (Trade name, marketed by Clontech Co.) according to 3′ RACE (Rapid Amplification of cDNA End) method. Double strand cDNA was prepared from the origin of each clone, i.e., poly (A)[0156] ⁺RNA in human placenta tissue. 27mer primer OX003-F1:
5′-CAAAACCCACAAGAAATTCACCAAGGC-3′ (SEQ ID NOS. 85)
containing the deduced initiation ATG codon region based on the information of nucleotide sequence obtained by SST, was prepared. PCR was performed with the said primer and adapter primer attached in the kit. Due to insufficient amplification of cDNA by only one-time PCR, 23mer primer OX003-F2: [0157]
5′-TCACCAAGGCTAACATGGTGGCC-3′ (SEQ ID NOS. 86)
was prepared additionally at 3′ end of OX003-F1 primer and then nested PCR was performed. cDNA which was amplified with clone OX003 specifically was separated with agarose-gel electrophoresis, ligated to pT7 Blue-2 T-Vector (Trade name, marketed by Novagen Co.) and transfected into [0158] E. coli DH5a to prepare the plasmid. First, Nucleotide sequences of 5′-end were determined, and the existence of nucleotide sequence OX003 SST cDNA was confirmed. Nucleotide sequence of full-length OX003 SST cDNA was determined and then sequence shown in SEQ ID NO. 9 was obtained. An open reading frame was determined and deduced amino acid sequence and nucleotide sequence shown in SEQ ID NOS. 7 and 8, respectively, were obtained.
It was indicated from the results of homology search for the public database of the nucleic acid sequences by using BLASTN and FASTA, and for the public database of the amino acid sequences by using BLASTX, BLASTP and FASTA, that there was no sequence identical to the polypeptide sequence and the nucleotide sequence of OX003 of the present invention. From these results, it was proved that polypeptide of the present invention was new secretary protein. [0159]

Example 4: Clone OA052

In Example relating to clone OA052 of the present invention, the same procedure as in Example of ON056 was used except for the following points. [0160]
(1) Preparation of Poly(A)[0161] ⁺RNA
Total RNA was prepared from human glioblastoma cell line T98G (ATCC No. CRL-1690) by TRIzol reagent. Poly(A)[0162] ⁺RNA was purified from the total RNA by mRNA Purification Kit.
(2) Cloning of a Full-length cDNA and Determination of Nucleotide Sequence [0163]
A full-length cDNA was cloned using Marathon cDNA Amplification Kit according to 3′ RACE method as described in Example of OX003. Double strand cDNA conjugating adapter was prepared from the origin of each clone, i.e., poly (A)[0164] ⁺RNA in human glioblastoma cell line T98G according to the method of the said kit. 27mer primer OA052-F1:
5′-ATGCCTAGAAGAGGACTGATTCTTCAC-3′ (SEQ ID NO. 87)
containing the deduced initiation ATG codon region based on the information of nucleotide sequence obtained by SST, was prepared. PCR was performed with the said primer and adapter primer attached in the kit. cDNA which was amplified with clone OA052 specifically was separated with recloning by the same method as Example of OX003. Full nucleotide sequence was determined and then sequence shown in SEQ ID NO. 12 was obtained. An open reading frame was determined and deduced amino acid sequence and nucleotide sequence shown in SEQ ID NOS. 10 and 11, respectively, were obtained. [0165]
It was indicated from the results of homology search for the public database of the nucleic acid sequences by using BLASTN and FASTA, and for the public database of the amino acid sequences by using BLASTX, BLASTP and FASTA, that there was no sequence identical to the polypeptide sequence and the nucleotide sequence of OA052 of the present invention. From these results, it was proved that polypeptide of the present invention was new secretary protein. [0166]

Example 5: Clone OC004

In Example relating to clone OC004 of the present invention, the same procedure as in Example of ON056 was used except for the following points. [0167]
(1) Preparation of Poly(A)[0168] ⁺RNA
Total RNA was prepared from human adult brain tissue by TRIzol reagent. Poly(A)[0169] ⁺RNA was purified from the total RNA by mRNA Purification Kit.
(2) Cloning of a Full-length cDNA and Determination of Nucleotide Sequence [0170]
A full-length cDNA was cloned using Marathon cDNA Amplification Kit according to 3′ RACE method as described in Example of OX003. Double strand cDNA was prepared from the origin of each clone, i.e., poly (A)[0171] ⁺RNA in human adult brain tissue. 27mer primer OC004-F1:
5′-ATGAGGAAAGGGAACCTTCTGCTGAGC-3′ (SEQ ID NOS. 88)
containing the deduced initiation ATG codon region based on the information of nucleotide sequence obtained by SST, was prepared. PCR was performed with the said primer and adapter primer attached in the kit. Due to insufficient amplification of cDNA by only one-time PCR, 18mer primer OC004-F2: [0172]
5′-TGAGCTTCCAGAGCTGTC-3′ (SEQ ID NOS. 89)
was prepared additionally at 3′ end of OC004-F1 primer and then nested PCR was performed. cDNA which was amplified with clone OC004 specifically was separated with recloning by the same method as Example of OX003. Full nucleotide sequence was determined and then sequence shown in SEQ ID NO. 15 was obtained. An open reading frame was determined and deduced amino acid sequence and nucleotide sequence shown in SEQ ID NOS. 13 and 14, respectively, were obtained. [0173]
It was indicated from the results of homology search for the public database of the nucleic acid sequences by using BLASTN and FASTA, and for the public database of the amino acid sequences by using BLASTX, BLASTP and FASTA, that there was no sequence identical to the polypeptide sequence and the nucleotide sequence of OC004 of the present invention. From these results, it was proved that polypeptide of the present invention was new secretary protein. [0174]

Example 6: Clone OM017

In Example relating to clone OM017 of the present invention, the same procedure as in Example of ON056 was used except for the following points. [0175]
(1) Preparation of Poly(A)[0176] ⁺RNA
Total RNA was prepared from human adult brain tissue by TRIzol reagent. Poly(A)[0177] ⁺RNA was purified from the total RNA by mRNA Purification Kit.
(2) Cloning of a Full-length cDNA and Determination of Nucleotide Sequence [0178]
A full-length cDNA was cloned using Marathon cDNA Amplification Kit according to 3′ RACE method as described in Example of OX003. Double strand cDNA was prepared from the origin of each clone, i.e., poly (A)[0179] ⁺RNA in human adult brain tissue. 27mer primer OM017-F3:
5′-GGGAAATGAAACATTTCTGTAACCTGC-3′ (SEQ ID NOS. 90)
containing the deduced initiation ATG codon region based on the information of nucleotide sequence obtained by SST, was prepared. PCR was performed with the said primer and adapter primer attached in the kit. Due to insufficient amplification of cDNA by only one-time PCR, 27mer primer OM017-F1: [0180]
5′-ATGAAACATTTCTGTAACCTGCTTTGT-3′ (SEQ ID NOS. 91)
was prepared additionally at 3′ end of OM017-F3 primer and then nested PCR was performed. cDNA which was amplified with clone OM017 specifically was separated with reckoning by the same method as Example of OX003. Full nucleotide sequence was determined and then sequence shown in SEQ ID NO. 18 was obtained. An open reading frame was determined and deduced amino acid sequence and nucleotide sequence shown in SEQ ID NOS. 16 and 17, respectively, were obtained. [0181]
It was indicated from the results of homology search for the public database of the nucleic acid sequences by using BLASTN and FASTA, and for the public database of the amino acid sequences by using BLASTX, BLASTP and FASTA, that there was no sequence identical to the polypeptide sequence and the nucleotide sequence of OM017 of the present invention. From these results, it was proved that polypeptide of the present invention was new secretary protein. [0182]
However, the search using BLASTX, BLASTP and FASTA revealed a significant homology between clone OM017 (region of 433th˜709th, 42nd˜225th, 170th˜399th and 1st˜224th amino acid in SEQ ID NO. 16) and Human DXS6673E (Candidate gene for Mental Retardation) (PRF Code 2218282A (Genbank Accession X95808) ) (region of 1083rd˜1358th, 758th˜932nd, 850th˜1081st and 739th˜965th amino acid) Based on these homologies, clone OM017 and Human DXS6673E were expected to share at least some activity. [0183]

Example 7: Clone OM101

In Example relating to clone OM101 of the present invention, the same procedure as in Example of ON056 was used except for the following points. [0184]
(1) Preparation of Poly(A)[0185] ⁺RNA
Total RNA was prepared from human adult brain tissue by TRIzol reagent. Poly(A)[0186] ⁺RNA was purified from the total RNA by mRNA Purification Kit.
(2) Cloning of a Full-length cDNA and Determination of Nucleotide Sequence [0187]
A full-length cDNA was cloned using Marathon cDNA Amplification Kit according to 3′ RACE method as described in Example of OX003. Double strand cDNA was prepared from the origin of each clone, i.e., poly (A)[0188] ⁺RNA in human adult brain tissue. 27mer primer OM101-F3:
5′-TGAAGTTGCAGATAATGAGGACTTACC-3′ (SEQ ID NOS. 92)
containing the deduced initiation ATG codon region based on the information of nucleotide sequence obtained by SST, was prepared. PCR was performed with the said primer and adapter primer attached in the kit. Due to insufficient amplification of cDNA by only one-time PCR, 27mer primer OM101-F1: [0189]
5′-ATGAGGACTTACCATTATATACCATTA-3′ (SEQ ID NOS. 93)
was prepared additionally at 3′ end of OM0101-F3 primer and then nested PCR was performed. cDNA which was amplified with clone OM101 specifically was separated with reckoning by the same method as Example of OX003. Full nucleotide sequence was determined and then sequence shown in SEQ ID NO. 21 was obtained. An open reading frame was determined and deduced amino acid sequence and nucleotide sequence shown in SEQ ID NOS. 19 and 20, respectively, were obtained. [0190]
It was indicated from the results of homology search for the public database of the nucleic acid sequences by using BLASTN and FASTA, and for the public database of the amino acid sequences by using BLASTX, BLASTP and FASTA, that there was no sequence identical to the polypeptide sequence and the nucleotide sequence of OM101 of the present invention. From these results, it was proved that polypeptide of the present invention was new secretary protein. [0191]
However, the search using BLASTX, BLASTP and FASTA revealed a significant homology between clone OM101 (region of 1st˜77th amino acid in SEQ ID NO. 19), and a lot of Cadherin family such as Human Cadherin-6 (Swiss Prot Accession P55285) (region of 1st˜77th amino acid) and Human Brain-Cadherin (Swiss Prot Accession P55289) (region of 1st˜78th amino acid). Based on these homologies, clone OM101 and Human Cadherin-6 and the other Cadherin family were expected to share at least some activity. [0192]

Example 8: Clone OM126

In Example relating to clone OM126 of the present invention, the same procedure as in Example of ON056 was used except for the following points. [0193]
(1) Preparation of Poly(A)[0194] ⁺RNA
Total RNA was prepared from human adult brain tissue by TRIzol reagent. Poly(A)[0195] ⁺RNA was purified from the total RNA by mRNA Purification Kit.
(2) Cloning of a Full-length cDNA and Determination of Nucleotide Sequence [0196]
Double strand cDNA was prepared from the origin of each clone, i.e., poly (A)[0197] ⁺RNA in human adult brain tissue. 27mer primer OM126-F3:
5′-AGGAAGGATGAGGAAGACCAGGCTCTG-3′ (SEQ ID NOS. 94)
containing the deduced initiation ATG codon region based on the information of nucleotide sequence obtained by SST, was prepared. cDNA which was amplified with clone OM126 specifically was separated with reckoning by the same method as Example of OX003. Full nucleotide sequence was determined and then sequence shown in SEQ ID NO. 24 was obtained. An open reading frame was determined and deduced amino acid sequence and nucleotide sequence shown in SEQ ID NOS. 22 and 23, respectively, were obtained. [0198]
It was indicated from the results of homology search for the public database of the nucleic acid sequences by using BLASTN and FASTA, and for the public database of the amino acid sequences by using BLASTX, BLASTP and FASTA, that there was no sequence identical to the polypeptide sequence and the nucleotide sequence of OM126 of the present invention. From these results, it was proved that polypeptide of the present invention was new secretary protein. [0199]
However, the search using BLASTX, BLASTP and FASTA revealed a significant homology between clone OM126 (region of 25th˜115th amino acid in SEQ ID NO.22), and immunoglobulin domain. Based on these homologies, clone OM126 and immunoglobulin superfamily were expected to share at least some activity. [0200]

Example 9: Clone OM160

In Example relating to clone OM160 of the present invention, the same procedure as in Example of ON056 was used except for the following points. [0201]
(1) Preparation of Poly(A)[0202] ⁺RNA
Total RNA was prepared from human adult brain tissue by TRIzol reagent. Poly(A)[0203] ⁺RNA was purified from the total RNA by mRNA Purification Kit.
(2) Cloning of a Full-length cDNA and Determination of Nucleotide Sequence [0204]
A full-length cDNA was cloned using GENETRAPPER cDNA Positive Selection System. First, dT-primed cDNA library was prepared from poly (A)+RNA in human adult brain tissue using pSPORT1 plasmid, as a vector, by Super Script Plasmid System for cDNA Synthesis and Plasmid Cloning. Next, after preparing biotinylated primer ON160-F1 (27mer): [0205]
5′ biotin-ATGCTTCAGTGGAGGAGAAGACACTGC-3′ (SEQ ID NO. 95)
based on the information of nucleotide sequence obtained by SST, plasmid hybridized specifically with the biotinylated primer were recovered from the cDNA library according to the method of Gene Trapper Kit and then transfected into [0206] E. coli DH10B. Colony hybridization with OM160 SST cDNA which was labeled with 32P-dCTP, as a probe, was performed by using Random Primer DNA Labeling kit according to known method to isolate the positive clone and to prepare the plasmid. Nucleotide sequence of full-length OM160 SST cDNA was determined by the same procedure as ON056 and then sequence shown in SEQ ID NO. 27 was obtained. An open reading frame was determined and deduced amino acid sequence and nucleotide sequence shown in SEQ ID NOS. 25 and 26, respectively, were obtained.
It was indicated from the results of homology search for the public database of the nucleic acid sequences by using BLASTN and FASTA, and for the public database of the amino acid sequences by using BLASTX, BLASTP and FASTA, that there was no sequence identical to the polypeptide sequence and the nucleotide sequence of OM160 of the present invention. From these results, it was proved that polypeptide of the present invention was new secretary protein. [0207]
However, the search using BLASTX, BLASTP and FASTA revealed a significant homology between clone OM160 (region of 153rd˜395th amino acid in SEQ ID NO. 25) and Drosophila neurogenic secreted signaling protein (Genepept Accession U41449) (region of 80th˜317th amino acid). Based on these homologies, clone OM160 and Drosophila neurogenic secreted signaling protein were expected to share at least some activity. [0208]

Example 10: Clone OMA016

In Example relating to clone OMA016 of the present invention, the same procedure as in Example of ON056 was used except for the following points. [0209]
(1) Preparation of Poly(A)[0210] ⁺RNA
Total RNA was prepared from human adult brain tissue by TRIzol reagent. Poly(A)[0211] ⁺RNA was purified from the total RNA by mRNA Purification
(2) Cloning of a Full-length cDNA and Determination of Nucleotide Sequence [0212]
A full-length cDNA was cloned using Marathon cDNA Amplification Kit according to 3′ RACE method as described in Example of OX003. Double strand cDNA was prepared from the origin of each clone, i.e., poly (A)[0213] ⁺RNA in human adult brain tissue. 27mer primer OMA016-F1:
5′-AGAAATGGTGAATGCCTGCTGGTGTGG-3′ (SEQ ID NOS. 96)
containing the deduced initiation ATG codon region based on the information of nucleotide sequence obtained by SST, was prepared. PCR was performed with the said primer and adapter primer attached in the kit. There existed two kinds of cDNAs which were amplified with clone OMA016 specifically and which were named OMA016a and OMA016b. These two were separated with recloning by the same method as Example of OX003. Full nucleotide sequences were determined and then sequences shown in SEQ ID NOS. 30 and 33 were obtained. Each open reading frame was determined and reduced amino acid sequences and nucleotide sequences shown in SEQ ID NOS. 28, 31 and SEQ ID NOS. 29, 32, respectively, were obtained. [0214]
It was indicated from the results of homology search for the public database of the nucleic acid sequences by using BLASTN and FASTA, and for the public database of the amino acid sequences by using BLASTX, BLASTP and FASTA, that there was no sequence identical to the polypeptide sequence and the nucleotide sequence of OMA016a and OMAO16b of the present invention. From these results, it was proved that polypeptide of the present invention was new secretary protein. [0215]

Example 11: Clone OMB130

In Example relating to clone OMB130 of the present invention, the same procedure as in Example of ON056 was used except for the following points. [0216]
(1) Preparation of Poly(A)[0217] ⁺RNA
Total RNA was prepared from human adult brain tissue by TRIzol reagent. Poly(A)[0218] ⁺RNA was purified from the total RNA by mRNA Purification
(2) Cloning of a Full-length cDNA and Determination of Nucleotide Sequence [0219]
Double strand cDNA was prepared from the origin of each clone, i.e., poly (A)[0220] ⁺RNA in human adult brain tissue. 27mer primer OMB130-F1:
5′-TCCTCTGACTTTTCTTCTGCAAGCTCC-3′ (SEQ ID NOS. 97)
containing the deduced initiation ATG codon region based on the information of nucleotide sequence obtained by SST, was prepared. cDNA which was amplified with clone OMB130 specifically was separated with reckoning by the same method as Example of OX003. Full nucleotide sequence was determined and then sequence shown in SEQ ID NO. 36 was obtained. An open reading frame was determined and deduced amino acid sequence and nucleotide sequence shown in SEQ ID NOS. 34 and 35, respectively, were obtained. [0221]
It was indicated from the results of homology search for the public database of the nucleic acid sequences by using BLASTN and FASTA, and for the public database of the amino acid sequences by using BLASTX, BLASTP and FASTA, that there was no sequence identical to the polypeptide sequence and the nucleotide sequence of OMB130 of the present invention. From these results, it was proved that polypeptide of the present invention was new secretary protein. [0222]
However, the search using BLASTX, BLASTP and FASTA revealed a significant homology between clone OMB130 (region of 10th˜177th amino acid in SEQ ID NO. 34), and Monkey Hepatitis A virus receptor (PRF Code 2220266A (Genbank Accession X98252) (region of 6th˜173rd amino acid. Based on these homologies, clone OMB130 and Monkey Hepatitis A virus receptor were expected to share at least some activity. [0223]

Example 12: Clone OMB142

In Example relating to clone OMB142 of the present invention, the same procedure as in Example of ON056 was used except for the following points. [0224]
(1) Preparation of Poly(A)[0225] ⁺RNA
Total RNA was prepared from human adult brain tissue by TRIzol reagent. Poly(A)[0226] ⁺RNA was purified from the total RNA by mRNA Purification Kit.
(2) Cloning of a Full-length cDNA and Determination of Nucleotide Sequence [0227]
A full-length cDNA was cloned using Marathon cDNA Amplification Kit according to 3′ RACE method as described in Example of OX003. Double strand cDNA was prepared from the origin of each clone, i.e., poly (A)[0228] ⁺RNA in human adult brain tissue. 27mer primer OMB142-F2:
5′-GCCCAAGGTCAAGGAGATGGTACGGAT-3′ (SEQ ID NOS. 98)
containing the deduced initiation ATG codon region based on the information of nucleotide sequence obtained by SST, was prepared. PCR was performed with the said primer and adapter primer attached in the kit. Due to insufficient amplification of cDNA by only one-time PCR, 28mer primer OMB142-F1: [0229]
5′-GGAGATGGTACGGATCTTAAGGACTGTG-3′ (SEQ ID NOS. 99)
was prepared additionally at 3′ end of OMB142-F2 primer and then nested PCR was performed. cDNA which was amplified with clone OMB142 specifically was separated with recloning by the same method as Example of OX003. Full nucleotide sequence was determined and then sequence shown in SEQ ID NO. 39 was obtained. An open reading frame was determined and deduced amino acid sequence and nucleotide sequence shown in SEQ ID NOS. 37 and 38, respectively, were obtained. [0230]
It was indicated from the results of homology search for the public database of the nucleic acid sequences by using BLASTN and FASTA, and for the public database of the amino acid sequences by using BLASTX, BLASTP and FASTA, that there was no sequence identical to the polypeptide sequence and the nucleotide sequence of OMB142 of the present invention. From these results, it was proved that polypeptide of the present invention was new secretary protein. [0231]

Example 13: Clone OTB033

In Example relating to clone OTB033 of the present invention, the same procedure as in Example of ON056 was used except for the following points. [0232]
(1) Preparation of Poly(A)[0233] ⁺RNA
Total RNA was prepared from human neuroblastoma cell line IMR-32 (ATCC No. CCL-127) by TRIzol reagent. Poly(A)[0234] ⁺RNA was purified from the total RNA by mRNA Purification Kit.
(2) Cloning of a Full-length cDNA and Determination of Nucleotide Sequence [0235]
A full-length cDNA was cloned using Marathon cDNA Amplification Kit according to 3′ RACE method as described in Example of OX003. Double strand cDNA was prepared from the origin of each clone, i.e., poly (A)[0236] ⁺RNA of IMR-32. 27mer primer OTB033-F1:
5′-TGCACTATCCAAAAGCTCCATGTACAC-3′ (SEQ ID NOS. 100)
containing the deduced initiation ATG codon region based on the information of nucleotide sequence obtained by SST, was prepared. PCR was performed with the said primer and adapter primer attached in the kit. Due to insufficient amplification of cDNA by only one-time PCR, 19mer primer OTB003-F2: [0237]
5′-CCATGTACACAGTGGGGGC-3′ (SEQ ID NOS.101)
was prepared additionally at 3′ end of OTB033-F1 primer and then nested PCR was performed. cDNA which was amplified with clone OTB033 specifically was separated with recloning by the same method as Example of OX003. Full nucleotide sequence was determined and then sequence shown in SEQ ID NO. 42 was obtained. An open reading frame was determined and deduced amino acid sequence and nucleotide sequence shown in SEQ ID NOS. 40 and 41, respectively, were obtained. [0238]
It was indicated from the results of homology search for the public database of the nucleic acid sequences by using BLASTN and FASTA, and for the public database of the amino acid sequences by using BLASTX, BLASTP and FASTA, that there was no sequence identical to the polypeptide sequence and the nucleotide sequence of OTB033 of the present invention. From these results, it was proved that polypeptide of the present invention was new secretary protein. [0239]

Example 14: Clone OVB100

In Example relating to clone OVB100 of the present invention, the same procedure as in Example of ON056 was used except for the following points. [0240]
(1) Preparation of Poly(A)[0241] ⁺RNA
Total RNA was prepared from human astrocytoma cell line CCF-STTG1 (ATCC No. CRL-1718) by TRIzol reagent. Poly(A)[0242] ⁺RNA was purified from the total RNA by mRNA Purification Kit.
(2) Cloning of a Full-length cDNA and Determination of Nucleotide Sequence [0243]
A full-length cDNA was cloned using Marathon cDNA Amplification Kit according to 3′ RACE method as described in Example of OX003. Double strand cDNA was prepared from the origin of each clone, i.e., poly (A)[0244] ⁺RNA of CCF-STTG1. 27mer primer OVB100-F1:
5′-CACTTGGTGTTTGATTTACCTAAGCAC-3′ (SEQ ID NOS. 102)
containing the deduced initiation ATG codon region based on the information of nucleotide sequence obtained by SST, was prepared. cDNA which was amplified with clone OVB100 specifically was separated with recloning by the same method as Example of OX003. Full nucleotide sequence was determined and then sequence shown in SEQ ID NO. 45 was obtained. An open reading frame was determined and deduced amino acid sequence and nucleotide sequence shown in SEQ ID NOS. 43 and 44, respectively, were obtained. [0245]
It was indicated from the results of homology search for the public database of the nucleic acid sequences by using BLASTN and FASTA, and for the public database of the amino acid sequences by using BLASTX, BLASTP and FASTA, that there was no sequence identical to the polypeptide sequence and the nucleotide sequence of OVB100 of the present invention. From these results, it was proved that polypeptide of the present invention was new secretary protein. [0246]

Example 15: Clone OAF062

In Example relating to clone OAF062 of the present invention, the same procedure as in Example of ON056 was used except for the following points. [0247]
(1) Preparation of Poly(A)[0248] ⁺RNA
Total RNA was prepared from human bone marrow stroma cell line HAS303 (provided from Prof. Keisuke Sotoyama, Dr. Makoto Aizawa, First Medicine, Tokyo Medical College) by TRIzol reagent. Poly(A)[0249] ⁺RNA was purified from the total RNA by mRNA Purification Kit.
(2) Cloning of a Full-length cDNA and Determination of Nucleotide Sequence [0250]
A full-length cDNA was cloned using Marathon cDNA Amplification Kit according to 3′ RACE method as described in Example of OX003. A full-length cDNA was cloned using Marathon cDNA Amplification Kit according to 3′ RACE method as described in Example of OX003. Double strand cDNA was prepared from the origin of each clone, i.e., poly (A)[0251] ⁺RNA of HAS303. 27mer primer OAF062-F2:
5′-GAGTTTCGTAAGCAAAATAGAGGACAG-3′ (SEQ ID NOS. 103)
containing the deduced initiation ATG codon region based on the information of nucleotide sequence obtained by SST, was prepared. PCR was performed with the said primer and adapter primer attached in the kit. Due to insufficient amplification of cDNA by only one-time PCR, 27mer primer OAF062-F3: [0252]
5′-TAGAGGACAGAAATGCAGTTCATGAAC-3′ (SEQ ID NOS. 104)
was prepared additionally at 3′ end of OAF062-F2 primer and then nested PCR was performed. cDNA which was amplified with clone OAF062 specifically was separated with reckoning by the same method as Example of OX003. Full nucleotide sequence was determined and then sequence shown in SEQ ID NO.48 was obtained. An open reading frame was determined and deduced amino acid sequence and nucleotide sequence shown in SEQ ID NOS. 46 and 47, respectively, were obtained. [0253]
It was indicated from the results of homology search for the public database of the nucleic acid sequences by using BLASTN and FASTA, and for the public database of the amino acid sequences by using BLASTX, BLASTP and FASTA, that there was no sequence identical to the polypeptide sequence and the nucleotide sequence of OAF062 of the present invention. From these results, it was proved that polypeptide of the present invention was new secretary protein. [0254]

Example 16: Clone OAF075

In Example relating to clone OAF075 of the present invention, the same procedure as in Example of ON056 was used except for the following points. [0255]
(1) Preparation of Poly(A)[0256] ⁺RNA
Total RNA was prepared from human bone marrow stroma cell line HAS303 (provided from Prof. Keisuke Sotoyama, Dr. Makoto Aizawa, First Medicine, Tokyo Medical College) by TRIzol reagent. Poly(A)[0257] ⁺RNA was purified from the total RNA by mRNA Purification Kit.
(2) Cloning of a Full-length cDNA and Determination of Nucleotide Sequence [0258]
A full-length cDNA was cloned using Marathon cDNA Amplification Kit according to 3′ RACE method as described in Example of OX003. Double strand cDNA was prepared from the origin of each clone, i.e., poly (A)[0259] ⁺RNA of HAS303. 28mer primer OAF075-F1:
5′-GACATGAGGTGGATACTGTTCATTGGGG-3′ (SEQ ID NOS. 105)
containing the deduced initiation ATG codon region based on the information of nucleotide sequence obtained by SST, was prepared. cDNA which was amplified with clone OAF075 specifically was separated with recloning by the same method as Example of OX003. Full nucleotide sequence was determined and then sequence shown in SEQ ID NO. 51 was obtained. An open reading frame was determined and deduced amino acid sequence and nucleotide sequence shown in SEQ ID NOS. 49 and 50, respectively, were obtained. [0260]
It was indicated from the results of homology search for the public database of the nucleic acid sequences by using BLASTN and FASTA, and for the public database of the amino acid sequences by using BLASTX, BLASTP and FASTA, that there was no sequence identical to the polypeptide sequence and the nucleotide sequence of OAF075 of the present invention. From these results, it was proved that polypeptide of the present invention was new secretary protein. [0261]
However, the search using BLASTX, BLASTP and FASTA revealed a significant homology between clone OAF075 (region of 1st˜421st amino acid in SEQ ID NO. 49), and Human Carboxypeptidase A2 (Swiss Prot Accession P48052) (region of 1st˜417th amino acid), Human Carboxypeptidase A1 (Swiss Prot Accession P15085) (region of 1st˜417th amino acid), Human Carboxypeptidase B (Swiss Prot Accession P15086) (region of 5th˜416th amino acid) and Human Mast Cell Carboxypeptidase A (Swiss Prot Accession P15088) (region of 1st˜412th amino acid). Based on these homologies, clone OAF075 and Carboxypeptidase family were expected to share at least some activity. [0262]

Example 17: Clone OAG119

In Example relating to clone OAG119 of the present invention, the same procedure as in Example of ON056 was used except for the following points. [0263]
(1) Preparation of Poly(A)[0264] ⁺RNA
Total RNA was prepared from human bone marrow stroma cell line LP101 (provided from Prof. Keisuke Sotoyama, Dr. Makoto Aizawa, First Medicine, Tokyo Medical College) by TRIzol reagent. Poly(A)[0265] ⁺RNA was purified from the total RNA by mRNA Purification Kit.
(2) Cloning of a Full-length cDNA and Determination of Nucleotide Sequence [0266]
A full-length cDNA was cloned using Marathon cDNA Amplification Kit according to 3′ RACE method as described in Example of OX003. Double strand cDNA was prepared from the origin of each clone, i.e., poly (A)[0267] ⁺RNA of LP101. 28mer primer OAG119-F1:
5′-TGGCGTGTAACTATGCTCATCATTGTTC-3′ (SEQ ID NOS. 106)
containing the deduced initiation ATG codon region based on the information of nucleotide sequence obtained by SST, was prepared. cDNA which was amplified with clone OAG119 specifically was separated with reckoning by the same method as Example of OX003. Full nucleotide sequence was determined and then sequence shown in SEQ ID NO. 54 was obtained. An open reading frame was determined and deduced amino acid sequence and nucleotide sequence shown in SEQ ID NOS. 52 and 53, respectively, were obtained. [0268]
It was indicated from the results of homology search for the public database of the nucleic acid sequences by using BLASTN and FASTA, and for the public database of the amino acid sequences by using BLASTX, BLASTP and FASTA, that there was no sequence identical to the polypeptide sequence and the nucleotide sequence of OAG119 of the present invention. From these results, it was proved that polypeptide of the present invention was new secretary protein. [0269]

Example 18: Clone OAH040

In Example relating to clone OAH040 of the present invention, the same procedure as in Example of ON056 was used except for the following points. [0270]
(1) Preparation of Poly(A)[0271] ⁺RNA
Total RNA was prepared from endothelial cell line of vein derived from human umbilical cord UV-EC-C (ATCC No. CRL-1730) by TRIzol reagent. Poly(A)[0272] ⁺RNA was purified from the total RNA by mRNA Purification Kit.
(2) Cloning of a Full-length cDNA and Determination of Nucleotide Sequence [0273]
A full-length cDNA was cloned using Marathon cDNA Amplification Kit according to 3′ RACE method as described in Example of OX003. Double strand cDNA was prepared from the origin of each clone, i.e., poly (A)[0274] ⁺RNA of HUV-EC-C. 28mer primer OAH040-F1:
5′-TTAGCCCACCCATGTTGATAGAACACCC-3′ (SEQ ID NOS. 107)
containing the deduced initiation ATG codon region based on the information of nucleotide sequence obtained by SST, was prepared. cDNA which was amplified with clone OAH040 specifically was separated with reckoning by the same method as Example of OX003. Full nucleotide sequence was determined and then sequence shown in SEQ ID NO. 57 was obtained. An open reading frame was determined and deduced amino acid sequence and nucleotide sequence shown in SEQ ID NOS. 55 and 56, respectively, were obtained. [0275]
It was indicated from the results of homology search for the public database of the nucleic acid sequences by using BLASTN and FASTA, and for the public database of the amino acid sequences by using BLASTX, BLASTP and FASTA, that there was no sequence identical to the polypeptide sequence and the nucleotide sequence of OAH040 of the present invention. From these results, it was proved that polypeptide of the present invention was new secretary protein. [0276]

Example 19: Clone OAH058

In Example relating to clone OAH058 of the present invention, the same procedure as in Example of OAH056 was used except for the following points. [0277]
(1) Preparation of Poly(A)[0278] ⁺RNA
Total RNA was prepared from endothelial cell line of vein derived from human umbilical cord HUV-EC-C (ATCC No. CRL-1730) by TRIzol reagent. Poly(A)[0279] ⁺RNA was purified from the total RNA by mRNA Purification Kit.
(2) Cloning of a Full-length cDNA and Determination of Nucleotide Sequence [0280]
A full-length cDNA was cloned using Marathon cDNA Amplification Kit according to 3′ RACE method as described in Example of OX003. Double strand cDNA was prepared from the origin of each clone, i.e., poly (A)[0281] ⁺RNA of HUV-EC-C. 28mer primer OAH058-F1:
5′-ACAATGTTGGCCTGTC TGCAAGCTTGTG-3′ (SEQ ID NOS. 108)
containing the deduced initiation ATG codon region based on the information of nucleotide sequence obtained by SST, was prepared. cDNA which was amplified with clone OAH058 specifically was separated with recloning by the same method as Example of OX003. Full nucleotide sequence was determined and then sequence shown in SEQ ID NO. 60 was obtained. An open reading frame was determined and deduced amino acid sequence and nucleotide sequence shown in SEQ ID NOS. 58 and 59, respectively, were obtained. [0282]
It was indicated from the results of homology search for the public database of the nucleic acid sequences by using BLASTN and FASTA, and for the public database of the amino acid sequences by using BLASTX, BLASTP and FASTA, that there was no sequence identical to the polypeptide sequence and the nucleotide sequence of OAH058 of the present invention. From these results, it was proved that polypeptide of the present invention was new secretary protein. [0283]

Example 20: Clone OM011

In Example relating to clone OM011 of the present invention, the same procedure as in Example of ON056 was used except for the following points. [0284]
(1) Preparation of Poly(A)[0285] ⁺RNA
Total RNA was prepared from human adult brain tissue by TRIzol reagent. Poly(A)[0286] ⁺RNA was purified from the total RNA by mRNA Purification Kit.
(2) Cloning of a Full-length cDNA and Determination of Nucleotide Sequence [0287]
A full-length cDNA was cloned using GENETRAPPER cDNA Positive Selection System. First, dT-primed cDNA library was prepared from poly (A)[0288] ⁺RNA in human adult brain tissue using pSPORT1 plasmid, as a vector, by Super Script Plasmid System for cDNA Synthesis and Plasmid Cloning. Next, after preparing biotinylated primer OM011-F1 (27mer):
5′ biotin-GAAGTGACTCTTCCTCTAGTTTGCCAC-3′ (SEQ ID NOS. 109)
based on the information of nucleotide sequence obtained by SST, plasmid hybridized specifically with the biotinylated primer were recovered from the cDNA library according to the method of Gene Trapper Kit and then transfected into [0289] E. coli DH10B. Colony hybridization with OM011 SST cDNA which was labeled with 32P-dCTP, as a probe, was performed by using Random Primer DNA Labeling kit according to known method to isolate the positive clone and to prepare the plasmid. Nucleotide sequence of full-length OM011 SST cDNA was determined by the same procedure as ON056 and then sequence shown in SEQ ID NO. 63 was obtained. An open reading frame was determined and deduced amino acid sequence and nucleotide sequence shown in SEQ ID NOS. 61 and 62, respectively, were obtained.
It was indicated from the results of homology search for the public database of the nucleic acid sequences by using BLASTN and FASTA, and for the public database of the amino acid sequences by using BLASTX, BLASTP and FASTA, that there was no sequence identical to the polypeptide sequence and the nucleotide sequence of OM011 of the present invention. From these results, it was proved that polypeptide of the present invention was new secretary protein. [0290]
However, the search using BLASTX, BLASTP and FASTA revealed a significant homology between clone OM011 (region of 26th˜396th amino acid in SEQ ID NO. 61) and Human Plasma-cell Glycoprotein PC-1 (Alkaline Phosphodiesterase I) (Swiss Prot Accession P22413) (region of 158th˜543rd amino acid). Based on these homologies, clone OM011 and Human Plasma-cell Glycoprotein PC-1 were expected to share at least some activity. [0291]

Example 21: Clone OM028

In Example relating to clone OM028 of the present invention, the same procedure as in Example of ON056 was used except for the following points. [0292]
(1) Preparation of Poly(A)[0293] ⁺RNA
Total RNA was prepared from human adult brain tissue by TRIzol reagent. Poly(A)[0294] ⁺RNA was purified from the total RNA by mRNA Purification Kit.
(2) Cloning of a Full-length cDNA and Determination of Nucleotide Sequence [0295]
A full-length cDNA was cloned using GENETRAPPER cDNA Positive Selection System. First, dT-primed cDNA library was prepared from poly (A)+RNA in human adult brain tissue using pSPORT1 plasmid, as a vector, by Super Script Plasmid System for cDNA Synthesis and Plasmid Cloning. Next, after preparing biotinylated primer OM028-F1 (27mer): [0296]
5′ biotin-ATGAAGGACATGCCACTCCGAATTCAT-3′ (SEQ ID NOS. 110)
based on the information of nucleotide sequence obtained by SST, plasmid hybridized specifically with the biotinylated primer were recovered from the cDNA library according to the method of Gene Trapper Kit and then transfected into [0297] E. coli DH10B. Colony hybridization with OM028 SST cDNA which was labeled with 32P-dCTP, as a probe, was performed by using Random Primer DNA Labeling kit according to known method to isolate the positive clone and to prepare the plasmid. Nucleotide sequence of full-length OM028 SST cDNA was determined by the same procedure as ON056 and then sequence shown in SEQ ID NO. 66 was obtained. An open reading frame was determined and deduced amino acid sequence and nucleotide sequence shown in SEQ ID NOS. 64 and 65, respectively, were obtained.
It was indicated from the results of homology search for the public database of the nucleic acid sequences by using BLASTN and FASTA, and for the public database of the amino acid sequences by using BLASTX, BLASTP and FASTA, that there was no sequence identical to the polypeptide sequence and the nucleotide sequence of OM028 of the present invention. From these results, it was proved that polypeptide of the present invention was new secretary protein. [0298]
However, the search using BLASTX, BLASTP and FASTA revealed a significant homology between clone OM028 (region of 1st˜708th amino acid in SEQ ID NO. 64) and many proteins containing Leu-rich repeat such as Mouse Leu-rich repeat protein (PRF Code 2212307A (GENBANK Accession D49802) (region of 1st˜707th amino acid). Based on these homologies, clone OM028 and certain proteins containing Leu-rich repeat were expected to share at least some activity. [0299]

Example 22: Clone OMB092

In Example relating to clone OMB092 of the present invention, the same procedure as in Example of ON056 was used except for the following points. [0300]
(1) Preparation of Poly(A)[0301] ⁺RNA
Total RNA was prepared from human adult brain tissue by TRIzol reagent. Poly(A)[0302] ⁺RNA was purified from the total RNA by mRNA Purification Kit.
(2) Cloning of a Full-length cDNA and Determination of Nucleotide Sequence [0303]
A full-length cDNA was cloned using Marathon cDNA Amplification Kit according to 3′ RACE method as described in Example of OX003. Double strand cDNA was prepared from the origin of each clone, i.e., poly (A)[0304] ⁺RNA in human adult brain tissue. 27mer primer OMB092-F1:
5′-ACTCACCTGGATCCCTAAGGGCACAGC-3′ (SEQ ID NOS. 111)
containing the deduced initiation ATG codon region based on the information of nucleotide sequence obtained by SST, was prepared. PCR was performed with the said primer and adapter primer attached in the kit. Due to insufficient amplification of cDNA by only one-time PCR, 28mer primer OMB092-F2: [0305]
5′-AGAATGAGCTATTACGGCAGCAGCTATC-3′ (SEQ ID NOS. 112)
was prepared additionally at 3′ end of OMB092-F1 primer and then nested PCR was performed. cDNA which was amplified with clone OMB092 specifically was separated with recloning by the same method as Example of OX003. Full nucleotide sequence was determined and then sequence shown in SEQ ID NO. 69 was obtained. An open reading frame was determined and deduced amino acid sequence and nucleotide sequence shown in SEQ ID NOS. 67 and 68, respectively, were obtained. [0306]
It was indicated from the results of homology search for the public database of the nucleic acid sequences by using BLASTN and FASTA, and for the public database of the amino acid sequences by using BLASTX, BLASTP and FASTA, that there was no sequence identical to the polypeptide sequence and the nucleotide sequence of OMB092 of the present invention. From these results, it was proved that polypeptide of the present invention was new secretary protein. [0307]
However, the search using BLASTX, BLASTP and FASTA revealed a significant homology between clone OMB092 (region of 1st˜254th amino acid in SEQ ID NO. 67) and many Potassium Channels family such as Rat Inward Rectifier Potassium Channel BIR9 (Swiss Prot Accession P52191) (region of 1st˜254th amino acid). Based on these homologies, clone OMB092 and Potassium Channel were expected to share at least some activity. [0308]

Example 23: Clone OMB108

In Example relating to clone OMB108 of the present invention, the same procedure as in Example of ON056 was used except for the following points. [0309]
(1) Preparation of Poly(A)[0310] ⁺RNA
Total RNA was prepared from human adult brain tissue by TRIzol reagent. Poly(A)[0311] ⁺RNA was purified from the total RNA by mRNA Purification Kit.
(2) Cloning of a Full-length cDNA and Determination of Nucleotide Sequence [0312]
A full-length cDNA was cloned using Marathon cDNA Amplification Kit according to 3′ RACE method as described in Example of OX003. Double strand cDNA was prepared from the origin of each clone, i.e., poly (A)[0313] ⁺RNA in human adult brain tissue. 27mer primer OMB108-F1:
5′-CTCTCTCCATCTGCTGTGGTTATGGCC-3′ (SEQ ID NOS. 113)
containing the deduced initiation ATG codon region based on the information of nucleotide sequence obtained by SST, was prepared. PCR was performed with the said primer and adapter primer attached in the kit. Due to insufficient amplification of cDNA by only one-time PCR, 22mer primer OMB108-F2: [0314]
5′-TGGTTATGGCCTGTCGCTGGAG-3′ (SEQ ID NOS. 114)[0315]
was prepared additionally at 3′ end of OMB108-F1 primer and then nested PCR was performed. cDNA which was amplified with clone OMB108 specifically was separated with recloning by the same method as Example of OX003. Full nucleotide sequence was determined and then sequence shown in SEQ ID NO. 72 was obtained. An open reading frame was determined and deduced amino acid sequence and nucleotide sequence shown in SEQ ID NOS. 70 and 71, respectively, were obtained. [0316]
It was indicated from the results of homology search for the public database of the nucleic acid sequences by using BLASTN and FASTA, and for the public database of the amino acid sequences by using BLASTX, BLASTP and FASTA, that there was no sequence identical to the polypeptide sequence and the nucleotide sequence of OMB108 of the present invention. From these results, it was proved that polypeptide of the present invention was new secretary protein. [0317]
However, the search using BLASTX, BLASTP and FASTA revealed a significant homology between clone OMB108 (region of 164th˜256th and 374th˜487th amino acid in SEQ ID NO. 70) and LDL-repeat region of many LDL receptors family such as Human Low-Density Lipoprotein Receptor Related Protein 10 (Swiss Prot Accession Q07954) or OMB108 (region of 47th˜158th and 259th˜370th amino acid in SEQ ID NO. 70) and CUB domain included in Human Bone Morphogenetic Protein 1 (Swiss Prot Accession P13497). That is to say, clone OMB108 proved to possess the common sequences of two parts of CUB domain and five parts of LDL-repeat at the extracell domain. Based on these homologies, clone OMB108, protein including LDL-repeat and protein including CUB domain were expected to share at least some activity. [0318]

Example 24: Clone OT007

In Example relating to clone OT007 of the present invention, the same procedure as in Example of ON056 was used except for the following points. [0319]
(1) Preparation of Poly(A)[0320] ⁺RNA
Total RNA was prepared from human neuroblastoma cell line IMR-32 (ATCC No. CCL-127) by TRIzol reagent. Poly(A)[0321] ⁺RNA was purified from the total RNA by mRNA Purification Kit.
(2) Cloning of a Full-length cDNA and Determination of Nucleotide Sequence [0322]
A full-length cDNA was cloned using GENETRAPPER cDNA Positive Selection System. First, dT-primed cDNA library was prepared from poly (A)[0323] ⁺RNA in IMR-32 using pSPORT1 plasmid, as a vector, by Super Script Plasmid System for cDNA Synthesis and Plasmid Cloning. Next, after preparing biotinylated primer OT007-F1 (27mer):
5′ biotin-AAAATGACTCCCCAGTCGCTGCTGCAG-3′ (SEQ ID NOS. 115)
based on the information of nucleotide sequence obtained by SST, plasmid hybridized specifically with the biotinylated primer were recovered from the cDNA library according to the method of Gene Trapper Kit and then transfected into [0324] E. coli DH10B. Colony hybridization with OT007 SST cDNA which was labeled with 32P-dCTP, as a probe, was performed by using Random Primer DNA Labeling kit according to known method to isolate the positive clone and to prepare the plasmid. Nucleotide sequence of full-length OT007 SST cDNA was determined by the same procedure as ON056 and then sequence shown in SEQ ID NO. 75 was obtained. An open reading frame was determined and deduced amino acid sequence and nucleotide sequence shown in SEQ ID NOS. 73 and 74, respectively, were obtained.
It was indicated from the results of homology search for the public database of the nucleic acid sequences by using BLASTN and FASTA, and for the public database of the amino acid sequences by using BLASTX, BLASTP and FASTA, that there was no sequence identical to the polypeptide sequence and the nucleotide sequence of OT007 of the present invention. From these results, it was proved that polypeptide of the present invention was new secretary protein. [0325]
However, the search using BLASTX, BLASTP and FASTA revealed a significant homology between clone OT007 (region of 217th˜660th amino acid in SEQ ID NO. 73) and transmembrane region of Secretin/Vasoactive Intestinal Peptide receptor superfamily such as Human Seven Transmembrane-domain receptor (Genepept Accession X82892), Rat Latrophilin-related protein 1 (Genepept Accession U78105), Human CD97 (Swiss Prot Accession P48960) etc. Based on these homologies, clone OT007 and certain proteins containing seven transmembrane region type of Secretin/Vasoactive Intestinal Peptide were expected to share at least some activity. [0326]

Example 25: Clone OAG051

In Example relating to clone OAG051 of the present invention, the same procedure as in Example of ON056 was used except for the following points. [0327]
(1) Preparation of Poly(A)[0328] ⁺RNA
Total RNA was prepared from human bone marrow stroma cell line LP101 (provided from Prof. Keisuke Sotoyama, Dr. Makoto Aizawa, First Medicine, Tokyo Medical College) by TRIzol reagent. Poly(A)[0329] ⁺RNA was purified from the total RNA by mRNA Purification Kit.
(2) Cloning of a Full-length cDNA and Determination of Nucleotide Sequence [0330]
A full-length cDNA was cloned using Marathon cDNA Amplification Kit according to 3′ RACE method as described in Example of OX003. Double strand cDNA was prepared from the origin of each clone, i.e., poly (A)[0331] ⁺RNA of LP101. 27mer primer OAG051-F1:
5′-GGAAATGTTTACATTTTTT GTTGACGTG-3′ (SEQ ID NOS. 116)[0332]
containing the deduced initiation ATG codon region based on the information of nucleotide sequence obtained by SST, was prepared. cDNA which was amplified with clone OAG051 specifically was separated with recloning by the same method as Example of OX003. Full nucleotide sequence was determined and then sequence shown in SEQ ID NO. 78 was obtained. An open reading frame was determined and deduced amino acid sequence and nucleotide sequence shown in SEQ ID NOS. 76 and 77, respectively, were obtained. [0333]
It was indicated from the results of homology search for the public database of, the nucleic acid sequences by using BLASTN and FASTA, and for the public database of the amino acid sequences by using BLASTX, BLASTP and FASTA, that there was no sequence identical to the polypeptide sequence and the nucleotide sequence of OAG051 of the present invention. From these results, it was proved that polypeptide of the present invention was new secretary protein. [0334]
However, the search using BLASTX, BLASTP and FASTA revealed a significant homology between clone OAG051 and many Frizzled family, for example, clone OAG051 (region of 4th˜703rd amino acid in SEQ ID NO. 76) and Mouse Frizzled-6 (PRF Code2208383E (Genebank Accession U43319) (region of 6th˜708th amino acid) or clone OAG051 (region of 1st˜627th amino acid in SEQ ID NO. 76) and Mouse Frizzled-3 (PRF Code 2208383E (Genebank Accession U43205) (region of 7th˜618th amino acid). Based on these homologies, clone clone OAG051 and Frizzled family were expected to share at least some activity. [0335]

Example 26: Clone OUB068

In Example relating to clone OUB068 of the present invention, the same procedure as in Example of ON056 was used except for the following points. [0336]
(1) Preparation of Poly(A)[0337] ⁺RNA
Total RNA was prepared from human osteosarcoma cell line U-2OS (ATCC No. HTB-96) by TRIzol reagent. Poly(A)[0338] ⁺RNA was purified from the total RNA by mRNA Purification Kit.
(2) Cloning of a Full-length cDNA and Determination of Nucleotide Sequence [0339]
A full-length cDNA was cloned using GENETRAPPER cDNA Positive Selection System. First, dT-primed cDNA library was prepared from poly (A)[0340] ⁺RNA in U-2OS using pSPORT1 plasmid, as a vector, by Super Script Plasmid System for cDNA Synthesis and Plasmid Cloning. Next, after preparing biotinylated primer OUB068-F1 (27mer):
5′ biotin-CACTCATGAAGGAAATTCCAGCGCTGC-3′ (SEQ ID NOS. 117)
based on the information of nucleotide sequence obtained by SST, plasmid hybridized specifically with the biotinylated primer were recovered from the cDNA library according to the method of Gene Trapper Kit and then transfected into [0341] E. coli DH10B. Colony hybridization with OUB068 SST cDNA which was labeled with 32P-dCTP, as a probe, was performed by using Random Primer DNA Labeling kit according to known method to isolate the positive clone and to prepare the plasmid. Nucleotide sequence of full-length OUB068 SST cDNA was determined by the same procedure as ON056 and then sequence shown in SEQ ID NO. 81 was obtained. An open reading frame was determined and deduced amino acid sequence and nucleotide sequence shown in SEQ ID NOS. 79 and 80, respectively, were obtained.
It was indicated from the results of homology search for the public database of the nucleic acid sequences by using BLASTN and FASTA, and for the public database of the amino acid sequences by using BLASTX, BLASTP and FASTA, that there was no sequence identical to the polypeptide sequence and the nucleotide sequence of OUB068 of the present invention. From these results, it was proved that polypeptide of the present invention was new secretary protein. [0342]
However, the search using BLASTX, BLASTP and FASTA revealed a significant homology between clone OUB068 (region of 5th˜386th amino acid in SEQ ID NO. 79) and Xenopus Unknown Transmembrane Protein (Genepept Accession X92871) (region of 3rd˜407th amino acid). Based on these homologies, clone OUB068 and Xenopus Unknown Transmembrane Protein were expected to share at least some activity. [0343]

0

SEQUENCE LISTING

<160> NUMBER OF SEQ ID NOS: 117

<210> SEQ ID NO 1

<211> LENGTH: 334

<212> TYPE: PRT

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 1

Met Asn Leu Ser Leu Val Leu Ala Ala Phe Cys Leu Gly Ile Ala Ser

-15 -10 -5

Ala Val Pro Lys Phe Asp Gln Asn Leu Asp Thr Lys Trp Tyr Gln Trp

-1 1 5 10 15

Lys Ala Thr His Arg Arg Leu Tyr Gly Ala Asn Glu Glu Gly Trp Arg

20 25 30

Arg Ala Val Trp Glu Lys Asn Met Lys Met Ile Glu Leu His Asn Gly

35 40 45

Glu Tyr Ser Gln Gly Lys His Gly Phe Thr Met Ala Met Asn Ala Phe

50 55 60

Gly Asp Met Thr Asn Glu Glu Phe Arg Gln Met Met Gly Cys Phe Arg

65 70 75

Asn Gln Lys Phe Arg Lys Gly Lys Val Phe Arg Glu Pro Leu Phe Leu

80 85 90 95

Asp Leu Pro Lys Ser Val Asp Trp Arg Lys Lys Gly Tyr Val Thr Pro

100 105 110

Val Lys Asn Gln Lys Gln Cys Gly Ser Cys Trp Ala Phe Ser Ala Thr

115 120 125

Gly Ala Leu Glu Gly Gln Met Phe Arg Lys Thr Gly Lys Leu Val Ser

130 135 140

Leu Ser Glu Gln Asn Leu Val Asp Cys Ser Arg Pro Gln Gly Asn Gln

145 150 155

Gly Cys Asn Gly Gly Phe Met Ala Arg Ala Phe Gln Tyr Val Lys Glu

160 165 170 175

Asn Gly Gly Leu Asp Ser Glu Glu Ser Tyr Pro Tyr Val Ala Val Asp

180 185 190

Glu Ile Cys Lys Tyr Arg Pro Glu Asn Ser Val Ala Asn Asp Thr Gly

195 200 205

Phe Thr Val Val Ala Pro Gly Lys Glu Lys Ala Leu Met Lys Ala Val

210 215 220

Ala Thr Val Gly Pro Ile Ser Val Ala Met Asp Ala Gly His Ser Ser

225 230 235

Phe Gln Phe Tyr Lys Ser Gly Ile Tyr Phe Glu Pro Asp Cys Ser Ser

240 245 250 255

Lys Asn Leu Asp His Gly Val Leu Val Val Gly Tyr Gly Phe Glu Gly

260 265 270

Ala Asn Ser Asn Asn Ser Lys Tyr Trp Leu Val Lys Asn Ser Trp Gly

275 280 285

Pro Glu Trp Gly Ser Asn Gly Tyr Val Lys Ile Ala Lys Asp Lys Asn

290 295 300

Asn His Cys Gly Ile Ala Thr Ala Ala Ser Tyr Pro Asn Val

305 310 315

<210> SEQ ID NO 2

<211> LENGTH: 1002

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 2

atgaatcttt cgctcgtcct ggctgccttt tgcttgggaa tagcctccgc tgttccaaaa 60

tttgaccaaa atttggatac aaagtggtac cagtggaagg caacacacag aagattatat 120

ggcgcgaatg aagaaggatg gaggagagca gtgtgggaaa agaatatgaa aatgattgaa 180

ctgcacaatg gggaatacag ccaagggaaa catggcttca caatggccat gaatgctttt 240

ggtgacatga ccaatgaaga attcaggcag atgatgggtt gctttcgaaa ccagaaattc 300

aggaagggga aagtgttccg tgagcctctg tttcttgatc ttcccaaatc tgtggattgg 360

agaaagaaag gctacgtgac gccagtgaag aatcagaaac agtgtggttc ttgttgggct 420

tttagtgcga ctggtgctct tgaaggacag atgttccgga aaactgggaa acttgtctca 480

ctgagcgagc agaatctggt ggactgttcg cgtcctcaag gcaatcaggg ctgcaatggt 540

ggcttcatgg ctagggcctt ccagtatgtc aaggagaacg gaggcctgga ctctgaggaa 600

tcctatccat atgtagcagt ggatgaaatc tgtaagtaca gacctgagaa ttctgttgct 660

aatgacactg gcttcacagt ggtcgcacct ggaaaggaga aggccctgat gaaagcagtc 720

gcaactgtgg ggcccatctc cgttgctatg gatgcaggcc attcgtcctt ccagttctac 780

aaatcaggca tttattttga accagactgc agcagcaaaa acctggatca tggtgttctg 840

gtggttggct acggctttga aggagcaaat tcgaataaca gcaagtattg gctcgtcaaa 900

aacagctggg gtccagaatg gggctcgaat ggctatgtaa aaatagccaa agacaagaac 960

aaccactgtg gaatcgccac agcagccagc taccccaatg tg 1002

<210> SEQ ID NO 3

<211> LENGTH: 1370

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<220> FEATURE:

<221> NAME/KEY: sig_peptide

<222> LOCATION: (60)..(110)

<221> NAME/KEY: mat_peptide

<222> LOCATION: (111)..(1061)

<221> NAME/KEY: CDS

<222> LOCATION: (60)..(1061)

<400> SEQUENCE: 3

ctcagaggct tgtttgctga gggtgcctgc gcagctgcga cggctgctgg ttttgaaac 59

atg aat ctt tcg ctc gtc ctg gct gcc ttt tgc ttg gga ata gcc tcc 107

Met Asn Leu Ser Leu Val Leu Ala Ala Phe Cys Leu Gly Ile Ala Ser

-15 -10 -5

gct gtt cca aaa ttt gac caa aat ttg gat aca aag tgg tac cag tgg 155

Ala Val Pro Lys Phe Asp Gln Asn Leu Asp Thr Lys Trp Tyr Gln Trp

-1 1 5 10 15

aag gca aca cac aga aga tta tat ggc gcg aat gaa gaa gga tgg agg 203

Lys Ala Thr His Arg Arg Leu Tyr Gly Ala Asn Glu Glu Gly Trp Arg

20 25 30

aga gca gtg tgg gaa aag aat atg aaa atg att gaa ctg cac aat ggg 251

Arg Ala Val Trp Glu Lys Asn Met Lys Met Ile Glu Leu His Asn Gly

35 40 45

gaa tac agc caa ggg aaa cat ggc ttc aca atg gcc atg aat gct ttt 299

Glu Tyr Ser Gln Gly Lys His Gly Phe Thr Met Ala Met Asn Ala Phe

50 55 60

ggt gac atg acc aat gaa gaa ttc agg cag atg atg ggt tgc ttt cga 347

Gly Asp Met Thr Asn Glu Glu Phe Arg Gln Met Met Gly Cys Phe Arg

65 70 75

aac cag aaa ttc agg aag ggg aaa gtg ttc cgt gag cct ctg ttt ctt 395

Asn Gln Lys Phe Arg Lys Gly Lys Val Phe Arg Glu Pro Leu Phe Leu

80 85 90 95

gat ctt ccc aaa tct gtg gat tgg aga aag aaa ggc tac gtg acg cca 443

Asp Leu Pro Lys Ser Val Asp Trp Arg Lys Lys Gly Tyr Val Thr Pro

100 105 110

gtg aag aat cag aaa cag tgt ggt tct tgt tgg gct ttt agt gcg act 491

Val Lys Asn Gln Lys Gln Cys Gly Ser Cys Trp Ala Phe Ser Ala Thr

115 120 125

ggt gct ctt gaa gga cag atg ttc cgg aaa act ggg aaa ctt gtc tca 539

Gly Ala Leu Glu Gly Gln Met Phe Arg Lys Thr Gly Lys Leu Val Ser

130 135 140

ctg agc gag cag aat ctg gtg gac tgt tcg cgt cct caa ggc aat cag 587

Leu Ser Glu Gln Asn Leu Val Asp Cys Ser Arg Pro Gln Gly Asn Gln

145 150 155

ggc tgc aat ggt ggc ttc atg gct agg gcc ttc cag tat gtc aag gag 635

Gly Cys Asn Gly Gly Phe Met Ala Arg Ala Phe Gln Tyr Val Lys Glu

160 165 170 175

aac gga ggc ctg gac tct gag gaa tcc tat cca tat gta gca gtg gat 683

Asn Gly Gly Leu Asp Ser Glu Glu Ser Tyr Pro Tyr Val Ala Val Asp

180 185 190

gaa atc tgt aag tac aga cct gag aat tct gtt gct aat gac act ggc 731

Glu Ile Cys Lys Tyr Arg Pro Glu Asn Ser Val Ala Asn Asp Thr Gly

195 200 205

ttc aca gtg gtc gca cct gga aag gag aag gcc ctg atg aaa gca gtc 779

Phe Thr Val Val Ala Pro Gly Lys Glu Lys Ala Leu Met Lys Ala Val

210 215 220

gca act gtg ggg ccc atc tcc gtt gct atg gat gca ggc cat tcg tcc 827

Ala Thr Val Gly Pro Ile Ser Val Ala Met Asp Ala Gly His Ser Ser

225 230 235

ttc cag ttc tac aaa tca ggc att tat ttt gaa cca gac tgc agc agc 875

Phe Gln Phe Tyr Lys Ser Gly Ile Tyr Phe Glu Pro Asp Cys Ser Ser

240 245 250 255

aaa aac ctg gat cat ggt gtt ctg gtg gtt ggc tac ggc ttt gaa gga 923

Lys Asn Leu Asp His Gly Val Leu Val Val Gly Tyr Gly Phe Glu Gly

260 265 270

gca aat tcg aat aac agc aag tat tgg ctc gtc aaa aac agc tgg ggt 971

Ala Asn Ser Asn Asn Ser Lys Tyr Trp Leu Val Lys Asn Ser Trp Gly

275 280 285

cca gaa tgg ggc tcg aat ggc tat gta aaa ata gcc aaa gac aag aac 1019

Pro Glu Trp Gly Ser Asn Gly Tyr Val Lys Ile Ala Lys Asp Lys Asn

290 295 300

aac cac tgt gga atc gcc aca gca gcc agc tac ccc aat gtg 1061

Asn His Cys Gly Ile Ala Thr Ala Ala Ser Tyr Pro Asn Val

305 310 315

tgagctgatg gatggtgagg aggaaggact taaggacagc atgtctgggg aaattttatc 1121

ttgaaactga ccaaacgctt attgtgtaag ataaaccagt tgaatcatgg aggatccaag 1181

ttgagatttt aattctgtga catttttaca agggtaaaat gttaccacta ctttaattat 1241

tgttatacac agctttatga tatcaaagac tcattgctta attctaagac ttttgaattt 1301

tcatttttta aaaagatgta caaaacagtt tgaaataaat tttaattcgt atataaaaaa 1361

aaaaaaaaa 1370

<210> SEQ ID NO 4

<211> LENGTH: 111

<212> TYPE: PRT

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 4

Met Leu Pro Leu Cys Ser Leu Phe Leu Phe Gly Ser Ser Ser Val Gly

-10 -5 -1 1

Val Lys Gln Tyr Gln Ala Leu Glu Leu Pro Leu Val Val Phe Val Thr

5 10 15

Tyr Leu Lys Met Ala Ala Cys Phe Leu Arg Ile Ser Gly Ser Ala Leu

20 25 30

Pro Val Phe Ile Cys Thr Phe Phe Ser His Cys Ala Ser Cys Thr His

35 40 45 50

Thr Pro Leu Pro His His Leu Pro Asn Leu Arg Leu Phe Gln Gln Phe

55 60 65

Leu Phe Arg Ala Gly Pro Cys Trp Asp Met Ile Ser Ile Lys Ser Glu

70 75 80

Gly Pro Asn Cys Ser Cys Pro Cys Ser Pro Tyr His Arg Pro Leu

85 90 95

<210> SEQ ID NO 5

<211> LENGTH: 333

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 5

atgttaccac tttgttcttt attccttttt ggatcatctt cagtgggggt aaaacagtat 60

caagctctag agctccctct ggtggttttt gtgacatatt tgaagatggc agcttgcttt 120

ttgagaattt ctggctctgc tctccctgtt tttatctgta cttttttttc tcattgtgcc 180

tcttgcacac acacacccct tccccaccat ctacccaatt tgcgcctgtt ccagcagttt 240

ctcttcaggg cagggccgtg ttgggacatg atttctatta agagtgaggg cccaaattgc 300

tcttgcccct gcagccctta tcacagaccc ctg 333

<210> SEQ ID NO 6

<211> LENGTH: 1086

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<220> FEATURE:

<221> NAME/KEY: sig_peptide

<222> LOCATION: (151)..(192)

<221> NAME/KEY: mat_peptide

<222> LOCATION: (193)..(483)

<221> NAME/KEY: CDS

<222> LOCATION: (151)..(483)

<400> SEQUENCE: 6

ttaattttaa actttgacac ctttaccctg ctaaacaata cagtacagtg accttcaaac 60

atttcagcag ccttcgggtt gttacatatt tattcttttt tgaagcccat cactacatcg 120

ccattacgtt ttacactgtg tatgtaacaa atg tta cca ctt tgt tct tta ttc 174

Met Leu Pro Leu Cys Ser Leu Phe

-10

ctt ttt gga tca tct tca gtg ggg gta aaa cag tat caa gct cta gag 222

Leu Phe Gly Ser Ser Ser Val Gly Val Lys Gln Tyr Gln Ala Leu Glu

-5 -1 1 5 10

ctc cct ctg gtg gtt ttt gtg aca tat ttg aag atg gca gct tgc ttt 270

Leu Pro Leu Val Val Phe Val Thr Tyr Leu Lys Met Ala Ala Cys Phe

15 20 25

ttg aga att tct ggc tct gct ctc cct gtt ttt atc tgt act ttt ttt 318

Leu Arg Ile Ser Gly Ser Ala Leu Pro Val Phe Ile Cys Thr Phe Phe

30 35 40

tct cat tgt gcc tct tgc aca cac aca ccc ctt ccc cac cat cta ccc 366

Ser His Cys Ala Ser Cys Thr His Thr Pro Leu Pro His His Leu Pro

45 50 55

aat ttg cgc ctg ttc cag cag ttt ctc ttc agg gca ggg ccg tgt tgg 414

Asn Leu Arg Leu Phe Gln Gln Phe Leu Phe Arg Ala Gly Pro Cys Trp

60 65 70

gac atg att tct att aag agt gag ggc cca aat tgc tct tgc ccc tgc 462

Asp Met Ile Ser Ile Lys Ser Glu Gly Pro Asn Cys Ser Cys Pro Cys

75 80 85 90

agc cct tat cac aga ccc ctg tagtcattat tggaacatgc tggtcttggg 513

Ser Pro Tyr His Arg Pro Leu

95

cctgcttttc tcagtcactg gagttctcca gtttgtaaga cggctcctcg cctcccctct 573

gcttcttcct gtacaaaggc cgtcaccctg caagccttgt tgctctcaac atgggttgtc 633

tctacttgtt cctattttag agttactgca gaatgccttg ccatctagct tggttgtagc 693

tggtaaccat aggtttttgt ttttttgcta tccttattgc actatgtttt atggaacaat 753

tggagaagat taaaaattca ccctgcccac tgggcgtggt ggctcacgcc tgtaatccca 813

gctctttggg aggccgaggc aggcagatca cgaggtcagg agatcgagac catcgtggct 873

aatacagtga aaccccgtct ctactaaaaa tgcaaaaaaa attagccggg catggtggtg 933

ggcgcctgta gtcccagcta cttgggaggc tgaggcagga gaatggcatg aattcgggag 993

gcggagcttg cagtgagcca agatcacgcc actgtactcc agcctgggca acagagcgag 1053

actccgtctc aaaaaaaaaa aaaaaaaaaa aaa 1086

<210> SEQ ID NO 7

<211> LENGTH: 111

<212> TYPE: PRT

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 7

Met Val Ala Thr Ser Thr Ala Val Ile Ser Gly Val Met Ser Leu Leu

-25 -20 -15

Gly Leu Ala Leu Ala Pro Ala Thr Gly Gly Gly Ser Leu Leu Leu Ser

-10 -5 -1 1 5

Thr Ala Gly Gln Gly Leu Ala Thr Ala Ala Gly Val Thr Ser Ile Val

10 15 20

Ser Gly Thr Leu Glu Arg Ser Lys Asn Lys Glu Ala Gln Ala Arg Ala

25 30 35

Glu Asp Ile Leu Pro Thr Tyr Asp Gln Glu Asp Arg Glu Asp Glu Glu

40 45 50

Glu Lys Ala Asp Tyr Val Thr Ala Ala Gly Lys Ile Ile Tyr Asn Leu

55 60 65 70

Arg Asn Thr Leu Lys Tyr Ala Lys Lys Asn Val Arg Ala Phe Trp

75 80 85

<210> SEQ ID NO 8

<211> LENGTH: 333

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 8

atggtggcca cctctactgc tgtcatctct ggagtgatga gcctcctggg tttagccctt 60

gccccagcaa caggaggagg aagcctgctg ctctccaccg ctggtcaagg tttggcaaca 120

gcagctgggg tcaccagcat cgtgagtggt acgttggaac gctccaaaaa taaagaagcc 180

caagcacggg cggaagacat actgcccacc tacgaccaag aggacaggga ggatgaggaa 240

gagaaggcag actatgtcac agctgctgga aagattatct ataatcttag aaacaccttg 300

aagtatgcca agaaaaacgt ccgtgcattt tgg 333

<210> SEQ ID NO 9

<211> LENGTH: 2604

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<220> FEATURE:

<221> NAME/KEY: sig_peptide

<222> LOCATION: (173)..(250)

<221> NAME/KEY: mat_peptide

<222> LOCATION: (251)..(505)

<221> NAME/KEY: CDS

<222> LOCATION: (173)..(505)

<400> SEQUENCE: 9

cgctcctctg tgtgaagacg tggagctaca agacggagat ctgtcccccg aagaaaaaat 60

atttttgaga gaatttccca gattgaaaga agatctgaaa gggaacattg acaagctccg 120

tgccctcgca gacgatattg acaaaaccca caagaaattc accaaggcta ac atg gtg 178

Met Val

-25

gcc acc tct act gct gtc atc tct gga gtg atg agc ctc ctg ggt tta 226

Ala Thr Ser Thr Ala Val Ile Ser Gly Val Met Ser Leu Leu Gly Leu

-20 -15 -10

gcc ctt gcc cca gca aca gga gga gga agc ctg ctg ctc tcc acc gct 274

Ala Leu Ala Pro Ala Thr Gly Gly Gly Ser Leu Leu Leu Ser Thr Ala

-5 -1 1 5

ggt caa ggt ttg gca aca gca gct ggg gtc acc agc atc gtg agt ggt 322

Gly Gln Gly Leu Ala Thr Ala Ala Gly Val Thr Ser Ile Val Ser Gly

10 15 20

acg ttg gaa cgc tcc aaa aat aaa gaa gcc caa gca cgg gcg gaa gac 370

Thr Leu Glu Arg Ser Lys Asn Lys Glu Ala Gln Ala Arg Ala Glu Asp

25 30 35 40

ata ctg ccc acc tac gac caa gag gac agg gag gat gag gaa gag aag 418

Ile Leu Pro Thr Tyr Asp Gln Glu Asp Arg Glu Asp Glu Glu Glu Lys

45 50 55

gca gac tat gtc aca gct gct gga aag att atc tat aat ctt aga aac 466

Ala Asp Tyr Val Thr Ala Ala Gly Lys Ile Ile Tyr Asn Leu Arg Asn

60 65 70

acc ttg aag tat gcc aag aaa aac gtc cgt gca ttt tgg taactcagag 515

Thr Leu Lys Tyr Ala Lys Lys Asn Val Arg Ala Phe Trp

75 80 85

ccaacccacg ctcggccaat gctaccaagc gtcttctgac cactggccaa gtctcctccc 575

ggagccgcgt gcaggtgcaa aaggcctttg cgggaacaac actggcgatg accaaaaatg 635

ctcgcgtgct gggaggtgtg atgtccgcct tctcccttgg ctatgacttg gccactctct 695

caaaggaatg gaagcacctg aaggaaggag caaggacaaa gtttgcggaa gagttgagag 755

ccaaggcctt ggagctggag aggaaactca cagaactcac ccagctctac aagagcttgc 815

agcagaaagt gaggtcaagg gccagagggg tggggaagga tttaactggg acctgcgaaa 875

ccgaggctta ctggaaggag ttaagggagc atgtgtggat gtggctgtgg ctgtgtgtgt 935

gtctgtgtgt ctgtgtgtat gtacagttta catgaatgtt cctcaggaca tggcatacaa 995

tggccttgga ggtccaaata atatcaagta catcttggag atgagggtgc ctgtcctgga 1055

cagacctcgg catgccttct gtttctcctt caatgctcct taaggcctat gtgctgggaa 1115

aagggtcttc cctgtttgtt tgtttgtttg tttgtttgtt tgttttgaga cggggtctct 1175

gttgcactcc agtctgggtg tcagaatgag accccatctc aaaaaaaaaa aaaaaaaaaa 1235

aaaagaagaa gaatacagtc atgtatctct tggtgacagg gacgcattct gataaatgtg 1295

tcattaggca attgcattgt agtgtgatta tcacagattg tacttataca aaacttagat 1355

ggcatagcct actgcatacc taggctatat gggagagcct attgctccca ggctacgcac 1415

ctgtacagca tgtgactact gaatactata ggcaattgca gcacaatggg aaatatttgt 1475

gtatctaaac atatgtaaac agagaaaaag gaaagtaaaa atatggcata aaagataaga 1535

attggctctc ctgtacaggg cacttactac gaatggagct tgcagggctg agagttgctc 1595

cagatgagtc agtgagtggt gaatgaatgt gaaggcctag ggcattactg tatactactg 1655

taggctttat aaacacagca cacttagggt acacaaaatg catattaaaa cattttcttc 1715

cttcagtata ttaggcaata ggaatttttc aagtccacta taaatcttat caaaccatgg 1775

ttgtatatgc agttgaccga aacattgtta ttggacacat aactatagtt gaaagaataa 1835

gcaaaaagtc tatctaggtg tgctgtcttg agcaactttt aattattctc ccgtcctgca 1895

atatgagtta atcttctctg atcgatgtag attccaggaa ggggtgtcca ggacaattac 1955

cttccttctg gagaaacttc ccttaatcaa ataagagaac ttcaaagaaa atccctccct 2015

gtgctttgga agggaaggga ggtgggcagc agtgggtcag agatagacct ttgttctctt 2075

atttctgagg cccttcagtc tcctttattc aaagcactca gcatgccaaa gcaccctatt 2135

ttagggtatc tttttctgag ccctaaacac tgtgttgggg atgtcaactg tgacaggaaa 2195

atatcttggg gccccagaat cactaaggaa aactcaagct tagggaaact tcttagggca 2255

aacccacctc ccactctatt caaagttatc tctctgctca ctgagataga tacatatctg 2315

attgcctcct ttggaaaggc taatcagaaa ctcaaaagaa tgcaactgtt tgtgtctcac 2375

ctatctgtga cctggaagct ccctccccac tgaaccaatg ttcttcttac atatattgat 2435

taatgtctta tgtctcccta aaatgtataa aaccaaggta tgccccaacc atcttggtca 2495

catgtcatca ggacttcctg agtctgtgtc acagtgtgtc ctcaaccttg gcaaaataaa 2555

ctttctaaat taacaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaa 2604

<210> SEQ ID NO 10

<211> LENGTH: 542

<212> TYPE: PRT

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 10

Met Pro Arg Arg Gly Leu Ile Leu His Thr Arg Thr His Trp Leu Leu

-30 -25 -20

Leu Gly Leu Ala Leu Leu Cys Ser Leu Val Leu Phe Met Tyr Leu Leu

-15 -10 -5

Glu Cys Ala Pro Gln Thr Asp Gly Asn Ala Ser Leu Pro Gly Val Val

-1 1 5 10

Gly Glu Asn Tyr Gly Lys Glu Tyr Tyr Gln Ala Leu Leu Gln Glu Gln

15 20 25 30

Glu Glu His Tyr Gln Thr Arg Ala Thr Ser Leu Lys Arg Gln Ile Ala

35 40 45

Gln Leu Lys Gln Glu Leu Gln Glu Met Ser Glu Lys Met Arg Ser Leu

50 55 60

Gln Glu Arg Arg Asn Val Gly Ala Asn Gly Ile Gly Tyr Gln Ser Asn

65 70 75

Lys Glu Gln Ala Pro Ser Asp Leu Leu Glu Phe Leu His Ser Gln Ile

80 85 90

Asp Lys Ala Glu Val Ser Ile Gly Ala Lys Leu Pro Ser Glu Tyr Gly

95 100 105 110

Val Ile Pro Phe Glu Ser Phe Thr Leu Met Lys Val Phe Gln Leu Glu

115 120 125

Met Gly Leu Thr Arg His Pro Glu Glu Lys Pro Val Arg Lys Asp Lys

130 135 140

Arg Asp Glu Leu Val Glu Val Ile Glu Ala Gly Leu Glu Val Ile Asn

145 150 155

Asn Pro Asp Glu Asp Asp Glu Gln Glu Asp Glu Glu Gly Pro Leu Gly

160 165 170

Glu Lys Leu Ile Phe Asn Glu Asn Asp Phe Val Glu Gly Tyr Tyr Arg

175 180 185 190

Thr Glu Arg Asp Lys Gly Thr Gln Tyr Glu Leu Phe Phe Lys Lys Ala

195 200 205

Asp Leu Thr Glu Tyr Arg His Val Thr Leu Phe Arg Pro Phe Gly Pro

210 215 220

Leu Met Lys Val Lys Ser Glu Met Ile Asp Ile Thr Arg Ser Ile Ile

225 230 235

Asn Ile Ile Val Pro Leu Ala Glu Arg Thr Glu Ala Phe Val Gln Phe

240 245 250

Met Gln Asn Phe Arg Asp Val Cys Ile His Gln Asp Lys Lys Ile His

255 260 265 270

Leu Thr Val Val Tyr Phe Gly Lys Glu Gly Leu Ser Lys Val Lys Ser

275 280 285

Ile Leu Glu Ser Val Thr Ser Glu Ser Asn Phe His Asn Tyr Thr Leu

290 295 300

Val Ser Leu Asn Glu Glu Phe Asn Arg Gly Arg Gly Leu Asn Val Gly

305 310 315

Ala Arg Ala Trp Asp Lys Gly Glu Val Leu Met Phe Phe Cys Asp Val

320 325 330

Asp Ile Tyr Phe Ser Ala Glu Phe Leu Asn Ser Cys Arg Leu Asn Ala

335 340 345 350

Glu Pro Gly Lys Lys Val Phe Tyr Pro Val Val Phe Ser Leu Tyr Asn

355 360 365

Pro Ala Ile Val Tyr Ala Asn Gln Glu Val Pro Pro Pro Val Glu Gln

370 375 380

Gln Leu Val His Lys Lys Asp Ser Gly Phe Trp Arg Asp Phe Gly Phe

385 390 395

Gly Met Thr Cys Gln Tyr Arg Ser Asp Phe Leu Thr Ile Gly Gly Phe

400 405 410

Asp Met Glu Val Arg Gly Trp Gly Gly Glu Asp Val His Leu Tyr Arg

415 420 425 430

Lys Tyr Leu His Gly Asp Leu Ile Val Ile Arg Thr Pro Val Pro Gly

435 440 445

Pro Phe His Leu Trp His Glu Lys Arg Cys Ala Asp Glu Leu Thr Pro

450 455 460

Glu Gln Tyr Arg Met Cys Ile Gln Ser Lys Ala Met Asn Glu Ala Ser

465 470 475

His Ser His Leu Gly Met Leu Val Phe Arg Glu Glu Ile Glu Thr His

480 485 490

Leu His Lys Gln Ala Tyr Arg Thr Asn Ser Glu Ala Val Gly

495 500 505

<210> SEQ ID NO 11

<211> LENGTH: 1626

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 11

atgcctagaa gaggactgat tcttcacacc cggacccact ggttgctgtt gggccttgct 60

ttgctctgca gtttggtatt atttatgtac ctcctggaat gtgcccccca gactgatgga 120

aatgcatctc ttcctggtgt tgttggggaa aattatggta aagagtatta tcaagccctc 180

ctacaggaac aagaagaaca ttatcagacc agggcaacca gtctgaaacg ccaaattgcc 240

caactaaaac aagaattaca agaaatgagt gagaagatgc ggtcactgca agaaagaagg 300

aatgtagggg ctaatggcat aggctatcag agcaacaaag agcaagcacc tagtgatctt 360

ttagagtttc ttcattccca aattgacaaa gctgaagtta gcataggggc caaactaccc 420

agtgagtatg gggtcattcc ctttgaaagt tttaccttaa tgaaagtatt tcaattggaa 480

atgggtctca ctcgccatcc tgaagaaaag ccagttagaa aagacaaacg agatgaattg 540

gtggaagtta ttgaagcggg cttggaggtc attaataatc ctgatgaaga tgatgaacaa 600

gaagatgagg agggtcccct tggagagaaa ctgatattta atgaaaatga cttcgtagaa 660

ggttattatc gcactgagag agataagggc acacagtatg aactcttttt taagaaagca 720

gaccttacgg aatatagaca tgtgaccctc ttccgccctt ttggacctct catgaaagtg 780

aagagtgaga tgattgacat cactagatca attattaata tcattgtgcc acttgctgaa 840

agaactgaag catttgtaca atttatgcag aacttcaggg atgtttgtat tcatcaagac 900

aagaagattc atctcacagt ggtgtatttt ggtaaagaag gactgtctaa ggtcaagtct 960

atcctagaat ctgtcaccag tgagtctaat tttcacaatt acaccttggt ctcattgaat 1020

gaagaattta atcgtggacg aggactaaat gtgggtgccc gagcttggga caagggagag 1080

gtcttgatgt ttttctgtga tgttgatatc tatttctcag ccgaattcct taacagctgc 1140

cggttaaatg ctgagccagg taagaaggtg ttttaccctg tggtgttcag tctttacaat 1200

cctgccattg tttatgccaa ccaggaagtg ccaccacctg tggagcagca gctggttcac 1260

aaaaaggatt ctggcttttg gcgagatttt ggctttggaa tgacttgtca gtatcgttca 1320

gatttcctga ccattggtgg atttgacatg gaagtgagag gttggggtgg agaagatgtt 1380

catctttatc gaaaatactt acatggtgac ctcattgtga ttcggactcc ggttcctggt 1440

cctttccacc tctggcatga aaagcgctgt gctgatgagc tgacccccga gcagtaccgc 1500

atgtgcatcc agtctaaagc catgaatgag gcctctcact cccacctggg aatgctggtc 1560

ttcagggagg aaatagagac gcatcttcat aaacaggcat acaggacaaa cagtgaagct 1620

gttggt 1626

<210> SEQ ID NO 12

<211> LENGTH: 3451

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<220> FEATURE:

<221> NAME/KEY: sig_peptide

<222> LOCATION: (41)..(142)

<221> NAME/KEY: mat_peptide

<222> LOCATION: (143)..(1666)

<221> NAME/KEY: CDS

<222> LOCATION: (41)..(1666)

<400> SEQUENCE: 12

aggcctagcg attttgttag gcaaatacac attaataaga atg cct aga aga gga 55

Met Pro Arg Arg Gly

-30

ctg att ctt cac acc cgg acc cac tgg ttg ctg ttg ggc ctt gct ttg 103

Leu Ile Leu His Thr Arg Thr His Trp Leu Leu Leu Gly Leu Ala Leu

-25 -20 -15

ctc tgc agt ttg gta tta ttt atg tac ctc ctg gaa tgt gcc ccc cag 151

Leu Cys Ser Leu Val Leu Phe Met Tyr Leu Leu Glu Cys Ala Pro Gln

-10 -5 -1 1

act gat gga aat gca tct ctt cct ggt gtt gtt ggg gaa aat tat ggt 199

Thr Asp Gly Asn Ala Ser Leu Pro Gly Val Val Gly Glu Asn Tyr Gly

5 10 15

aaa gag tat tat caa gcc ctc cta cag gaa caa gaa gaa cat tat cag 247

Lys Glu Tyr Tyr Gln Ala Leu Leu Gln Glu Gln Glu Glu His Tyr Gln

20 25 30 35

acc agg gca acc agt ctg aaa cgc caa att gcc caa cta aaa caa gaa 295

Thr Arg Ala Thr Ser Leu Lys Arg Gln Ile Ala Gln Leu Lys Gln Glu

40 45 50

tta caa gaa atg agt gag aag atg cgg tca ctg caa gaa aga agg aat 343

Leu Gln Glu Met Ser Glu Lys Met Arg Ser Leu Gln Glu Arg Arg Asn

55 60 65

gta ggg gct aat ggc ata ggc tat cag agc aac aaa gag caa gca cct 391

Val Gly Ala Asn Gly Ile Gly Tyr Gln Ser Asn Lys Glu Gln Ala Pro

70 75 80

agt gat ctt tta gag ttt ctt cat tcc caa att gac aaa gct gaa gtt 439

Ser Asp Leu Leu Glu Phe Leu His Ser Gln Ile Asp Lys Ala Glu Val

85 90 95

agc ata ggg gcc aaa cta ccc agt gag tat ggg gtc att ccc ttt gaa 487

Ser Ile Gly Ala Lys Leu Pro Ser Glu Tyr Gly Val Ile Pro Phe Glu

100 105 110 115

agt ttt acc tta atg aaa gta ttt caa ttg gaa atg ggt ctc act cgc 535

Ser Phe Thr Leu Met Lys Val Phe Gln Leu Glu Met Gly Leu Thr Arg

120 125 130

cat cct gaa gaa aag cca gtt aga aaa gac aaa cga gat gaa ttg gtg 583

His Pro Glu Glu Lys Pro Val Arg Lys Asp Lys Arg Asp Glu Leu Val

135 140 145

gaa gtt att gaa gcg ggc ttg gag gtc att aat aat cct gat gaa gat 631

Glu Val Ile Glu Ala Gly Leu Glu Val Ile Asn Asn Pro Asp Glu Asp

150 155 160

gat gaa caa gaa gat gag gag ggt ccc ctt gga gag aaa ctg ata ttt 679

Asp Glu Gln Glu Asp Glu Glu Gly Pro Leu Gly Glu Lys Leu Ile Phe

165 170 175

aat gaa aat gac ttc gta gaa ggt tat tat cgc act gag aga gat aag 727

Asn Glu Asn Asp Phe Val Glu Gly Tyr Tyr Arg Thr Glu Arg Asp Lys

180 185 190 195

ggc aca cag tat gaa ctc ttt ttt aag aaa gca gac ctt acg gaa tat 775

Gly Thr Gln Tyr Glu Leu Phe Phe Lys Lys Ala Asp Leu Thr Glu Tyr

200 205 210

aga cat gtg acc ctc ttc cgc cct ttt gga cct ctc atg aaa gtg aag 823

Arg His Val Thr Leu Phe Arg Pro Phe Gly Pro Leu Met Lys Val Lys

215 220 225

agt gag atg att gac atc act aga tca att att aat atc att gtg cca 871

Ser Glu Met Ile Asp Ile Thr Arg Ser Ile Ile Asn Ile Ile Val Pro

230 235 240

ctt gct gaa aga act gaa gca ttt gta caa ttt atg cag aac ttc agg 919

Leu Ala Glu Arg Thr Glu Ala Phe Val Gln Phe Met Gln Asn Phe Arg

245 250 255

gat gtt tgt att cat caa gac aag aag att cat ctc aca gtg gtg tat 967

Asp Val Cys Ile His Gln Asp Lys Lys Ile His Leu Thr Val Val Tyr

260 265 270 275

ttt ggt aaa gaa gga ctg tct aag gtc aag tct atc cta gaa tct gtc 1015

Phe Gly Lys Glu Gly Leu Ser Lys Val Lys Ser Ile Leu Glu Ser Val

280 285 290

acc agt gag tct aat ttt cac aat tac acc ttg gtc tca ttg aat gaa 1063

Thr Ser Glu Ser Asn Phe His Asn Tyr Thr Leu Val Ser Leu Asn Glu

295 300 305

gaa ttt aat cgt gga cga gga cta aat gtg ggt gcc cga gct tgg gac 1111

Glu Phe Asn Arg Gly Arg Gly Leu Asn Val Gly Ala Arg Ala Trp Asp

310 315 320

aag gga gag gtc ttg atg ttt ttc tgt gat gtt gat atc tat ttc tca 1159

Lys Gly Glu Val Leu Met Phe Phe Cys Asp Val Asp Ile Tyr Phe Ser

325 330 335

gcc gaa ttc ctt aac agc tgc cgg tta aat gct gag cca ggt aag aag 1207

Ala Glu Phe Leu Asn Ser Cys Arg Leu Asn Ala Glu Pro Gly Lys Lys

340 345 350 355

gtg ttt tac cct gtg gtg ttc agt ctt tac aat cct gcc att gtt tat 1255

Val Phe Tyr Pro Val Val Phe Ser Leu Tyr Asn Pro Ala Ile Val Tyr

360 365 370

gcc aac cag gaa gtg cca cca cct gtg gag cag cag ctg gtt cac aaa 1303

Ala Asn Gln Glu Val Pro Pro Pro Val Glu Gln Gln Leu Val His Lys

375 380 385

aag gat tct ggc ttt tgg cga gat ttt ggc ttt gga atg act tgt cag 1351

Lys Asp Ser Gly Phe Trp Arg Asp Phe Gly Phe Gly Met Thr Cys Gln

390 395 400

tat cgt tca gat ttc ctg acc att ggt gga ttt gac atg gaa gtg aga 1399

Tyr Arg Ser Asp Phe Leu Thr Ile Gly Gly Phe Asp Met Glu Val Arg

405 410 415

ggt tgg ggt gga gaa gat gtt cat ctt tat cga aaa tac tta cat ggt 1447

Gly Trp Gly Gly Glu Asp Val His Leu Tyr Arg Lys Tyr Leu His Gly

420 425 430 435

gac ctc att gtg att cgg act ccg gtt cct ggt cct ttc cac ctc tgg 1495

Asp Leu Ile Val Ile Arg Thr Pro Val Pro Gly Pro Phe His Leu Trp

440 445 450

cat gaa aag cgc tgt gct gat gag ctg acc ccc gag cag tac cgc atg 1543

His Glu Lys Arg Cys Ala Asp Glu Leu Thr Pro Glu Gln Tyr Arg Met

455 460 465

tgc atc cag tct aaa gcc atg aat gag gcc tct cac tcc cac ctg gga 1591

Cys Ile Gln Ser Lys Ala Met Asn Glu Ala Ser His Ser His Leu Gly

470 475 480

atg ctg gtc ttc agg gag gaa ata gag acg cat ctt cat aaa cag gca 1639

Met Leu Val Phe Arg Glu Glu Ile Glu Thr His Leu His Lys Gln Ala

485 490 495

tac agg aca aac agt gaa gct gtt ggt tgaaatcata attaatgcgt 1686

Tyr Arg Thr Asn Ser Glu Ala Val Gly

500 505

tactgtatga accacaaaac agcactattt atttagcctt acttctactt ccagatgcag 1746

tgcctctttt ggagaagaca tgtttatttt tcatgttctt tctgacatta ctttagcaat 1806

tcaacttgat gtgagaagaa aaaacaaatg tttcaacaca aaatctctgt tttgtgagaa 1866

tactgcacta tggaataatt gacaaattga aatctcatat ttgtcccaaa agttgttttg 1926

agttagttct acctggtgcc catgttctga ttgtgtgtgg gattgcatgg tgtcctgatt 1986

gcatctaggt ggagcggatg gaatgtgctg ggccactgtt gggtggagag cagcacattc 2046

ttacagagga gatggagcgt tatgagcata gtatgtggat aggtatcttc acctgcccgc 2106

ccctgagtca gcctccttga cttgatagct tgaagaatcc ttttccactg aaatagagga 2166

taattaattg acacatctga aatccccaat caatcaatca agagaaaggt agaactaaaa 2226

actccttaac ttactgttgc ttacacccct gaaagtctgt ttttaagcaa atgggtaata 2286

gtagaaaata ggttagaatc tatggcttga ttaaaaatat gttattacat tatcatgttc 2346

aggattagga ttagtagtca gttgctgtaa actattttga acaaacagaa aagaacacgg 2406

aaacattttt aacagagcat ttaattatgt tggaatacag gatcctagct ctgtctggga 2466

acattagctt atgtgagcca gctctatcag ggtcttccca tggtggttca gaatagatga 2526

gcatagcatg gttttgtttg tttttgcttt caattttcta atttggcatg gatccatatg 2586

tatttactat cctttttcta atatattaat atatgctaca tttgtatttg cattactata 2646

atactttgag ttgaaaaaga gtttcattgt ggagagaaaa agcaaatggt atgccacaag 2706

atcactctga tttgagaaaa gggaggaggg gaagatagtc tgaatggaaa tctgaaatac 2766

ggaatgtttt agagaaatat gtcacttgca tatagaatgt tttaattgag gtataaatta 2826

atgagacaaa gtgaaaaaga aattatattc agataggact gcactacatt atttgtcaca 2886

catggatctg ttaccatcag gtcaattcct agtatgcata aattttttaa cccttttaaa 2946

agagacctat gttgaaaacc cctgaaaatt cactgaagaa aaatcattac tctttttctc 3006

agtaaatcat atcatctgaa atattacaaa tttcaaattt ctaggtgcta tattaattca 3066

atattacaat aactcttacc taattattct tacaagtttt aagttgtggt agtttagtga 3126

tttttttaaa agatgtgtga aatgttctct gcaaaataat tcaggccact gtctcctttt 3186

atatattatt ataattattt attatgaaga ccagtgaatt acgatattta aagtgagaga 3246

acttaattat ttgcaaaggt aagttacagc ttgttttttg agagaatcaa atgagtttac 3306

ttttgttcct gttgttttta actagcttta agtttaaaga tggaagctaa gcaatggaaa 3366

tgctatacgt ttttgacatt tattaaatgg taccaataaa gtattttatt accaaaaaaa 3426

aaaaaaaaaa aaaaaaaaaa aaaaa 3451

<210> SEQ ID NO 13

<211> LENGTH: 119

<212> TYPE: PRT

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 13

Met Arg Lys Gly Asn Leu Leu Leu Ser Trp Leu Leu Gly Pro Glu Leu

-15 -10 -5

Pro Glu Leu Ser Pro Arg Ala Arg Lys Ala Asp Leu Lys Asp Glu Asn

-1 1 5 10 15

Leu Lys Phe Ser Cys Trp Trp Glu Pro Arg Lys Thr Ala Gly Val Leu

20 25 30

Thr Trp Pro Phe Leu Ala Glu Leu Ala Glu Val Gly Val Leu Ala Asp

35 40 45

Gly Met Tyr Leu Gly Ala Val Ser Val Ala Gln Gln Arg Cys Arg Ala

50 55 60

Asp Trp Leu Ser His Trp Val Leu Pro Ala Gly Ser Pro Leu His Trp

65 70 75

Ala Phe Thr Gln Pro Cys Ser Trp Val Ser Leu Pro Cys Lys Gln Ser

80 85 90 95

His Asn Asn Thr Arg Ile Val

100

<210> SEQ ID NO 14

<211> LENGTH: 357

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 14

atgaggaaag ggaaccttct gctgagctgg cttctggggc ctgagcttcc agagctgtcc 60

ccaagggcta ggaaggccga cctgaaggat gagaacctca aattcagttg ctggtgggag 120

ccaaggaaga cggcgggtgt tctaacgtgg ccctttctgg ctgagctggc ggaagtgggc 180

gttttggccg atgggatgta tctcggcgct gtgtctgtgg cccagcaaag gtgcagggct 240

gactggctga gccactgggt tctacccgca ggctccccac tgcactgggc tttcacacag 300

ccatgctctt gggtttccct cccttgtaag cagagtcata ataacacacg aatagtc 357

<210> SEQ ID NO 15

<211> LENGTH: 814

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<220> FEATURE:

<221> NAME/KEY: sig_peptide

<222> LOCATION: (62)..(112)

<221> NAME/KEY: mat_peptide

<222> LOCATION: (113)..(418)

<221> NAME/KEY: CDS

<222> LOCATION: (62)..(418)

<400> SEQUENCE: 15

caaaaatata agcatcagct gaggtgatat tagttcagtc acctaacaac tcctagaaga 60

g atg agg aaa ggg aac ctt ctg ctg agc tgg ctt ctg ggg cct gag ctt 109

Met Arg Lys Gly Asn Leu Leu Leu Ser Trp Leu Leu Gly Pro Glu Leu

-15 -10 -5

cca gag ctg tcc cca agg gct agg aag gcc gac ctg aag gat gag aac 157

Pro Glu Leu Ser Pro Arg Ala Arg Lys Ala Asp Leu Lys Asp Glu Asn

-1 1 5 10 15

ctc aaa ttc agt tgc tgg tgg gag cca agg aag acg gcg ggt gtt cta 205

Leu Lys Phe Ser Cys Trp Trp Glu Pro Arg Lys Thr Ala Gly Val Leu

20 25 30

acg tgg ccc ttt ctg gct gag ctg gcg gaa gtg ggc gtt ttg gcc gat 253

Thr Trp Pro Phe Leu Ala Glu Leu Ala Glu Val Gly Val Leu Ala Asp

35 40 45

ggg atg tat ctc ggc gct gtg tct gtg gcc cag caa agg tgc agg gct 301

Gly Met Tyr Leu Gly Ala Val Ser Val Ala Gln Gln Arg Cys Arg Ala

50 55 60

gac tgg ctg agc cac tgg gtt cta ccc gca ggc tcc cca ctg cac tgg 349

Asp Trp Leu Ser His Trp Val Leu Pro Ala Gly Ser Pro Leu His Trp

65 70 75

gct ttc aca cag cca tgc tct tgg gtt tcc ctc cct tgt aag cag agt 397

Ala Phe Thr Gln Pro Cys Ser Trp Val Ser Leu Pro Cys Lys Gln Ser

80 85 90 95

cat aat aac aca cga ata gtc taacgctggg tattctggtc agcagaggtc 448

His Asn Asn Thr Arg Ile Val

100

cttgagtcac agtgttactg aaatggttct gagcctgaga atctctttgg cctctgaaag 508

ggcagggcag gtgggcaccg acttcctgcc agtcctttca ggtttcctgt tcaaagccag 568

tcctgttggt ggaggggatc accgagagtg tctgtatcat tttgtagccc ttttctctga 628

cgttttctgg tagaaaatgt cccttgtcaa aatgctaata attatcataa taatctgctt 688

tccaaccaac ttccacaagt gacaacctgt gtagaactgt gataaaggtt tgcataatgt 748

agggtttgta ccaagtgtgt gtaagtttct gttaaataaa aagtctgttt ccaaaaaaaa 808

aaaaaa 814

<210> SEQ ID NO 16

<211> LENGTH: 714

<212> TYPE: PRT

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 16

Met Lys His Phe Cys Asn Leu Leu Cys Ile Leu Met Phe Cys Asn Gln

-15 -10 -5 -1

Gln Ser Val Cys Asp Pro Pro Ser Gln Asn Asn Ala Ala Asn Ile Ser

1 5 10 15

Met Val Gln Ala Ala Ser Ala Gly Pro Pro Ser Leu Arg Lys Asp Ser

20 25 30

Thr Pro Val Ile Ala Asn Val Val Ser Leu Ala Ser Ala Pro Ala Ala

35 40 45

Gln Pro Thr Val Asn Ser Asn Ser Val Leu Gln Gly Ala Val Pro Thr

50 55 60

Val Thr Ala Lys Ile Ile Gly Asp Ala Ser Thr Gln Thr Asp Ala Leu

65 70 75 80

Lys Leu Pro Pro Ser Gln Pro Pro Arg Leu Leu Lys Asn Lys Ala Leu

85 90 95

Leu Cys Lys Pro Ile Thr Gln Thr Lys Ala Thr Ser Cys Lys Pro His

100 105 110

Thr Gln Asn Lys Glu Cys Gln Thr Glu Asp Thr Pro Ser Gln Pro Gln

115 120 125

Ile Ile Val Val Pro Val Pro Val Pro Val Phe Val Pro Ile Pro Leu

130 135 140

His Leu Tyr Thr Gln Tyr Ala Pro Val Pro Phe Gly Ile Pro Val Pro

145 150 155 160

Met Pro Val Pro Met Leu Ile Pro Ser Ser Met Asp Ser Glu Asp Lys

165 170 175

Val Thr Glu Ser Ile Glu Asp Ile Lys Glu Lys Leu Pro Thr His Pro

180 185 190

Phe Glu Ala Asp Leu Leu Glu Met Ala Glu Met Ile Ala Glu Asp Glu

195 200 205

Glu Lys Lys Thr Leu Ser Gln Gly Glu Ser Gln Thr Ser Glu His Glu

210 215 220

Leu Phe Leu Asp Thr Lys Ile Phe Glu Lys Asp Gln Gly Ser Thr Tyr

225 230 235 240

Ser Gly Asp Leu Glu Ser Glu Ala Val Ser Thr Leu His Ser Trp Glu

245 250 255

Glu Glu Leu Asn His Tyr Ala Leu Lys Ser Asn Ala Val Gln Glu Ala

260 265 270

Asp Ser Glu Leu Lys Gln Phe Ser Lys Gly Glu Thr Glu Gln Asp Leu

275 280 285

Glu Ala Asp Phe Pro Ser Asp Ser Phe Asp Pro Leu Asn Lys Gly Gln

290 295 300

Gly Ile Gln Ala Arg Ser Arg Thr Arg Arg Arg His Arg Asp Gly Phe

305 310 315 320

Pro Gln Pro Arg Arg Arg Gly Arg Lys Lys Ser Ile Val Ala Val Glu

325 330 335

Pro Arg Ser Leu Ile Gln Gly Ala Phe Gln Gly Cys Ser Val Ser Gly

340 345 350

Met Thr Leu Lys Tyr Met Tyr Gly Val Asn Ala Trp Lys Asn Trp Val

355 360 365

Gln Trp Lys Asn Ala Lys Glu Glu Gln Gly Asp Leu Lys Cys Gly Gly

370 375 380

Val Glu Gln Ala Ser Ser Ser Pro Arg Ser Asp Pro Leu Gly Ser Thr

385 390 395 400

Gln Asp His Ala Leu Ser Gln Glu Ser Ser Glu Pro Gly Cys Arg Val

405 410 415

Arg Ser Ile Lys Leu Lys Glu Asp Ile Leu Ser Cys Thr Phe Ala Glu

420 425 430

Leu Ser Leu Gly Leu Cys Gln Phe Ile Gln Glu Val Arg Arg Pro Asn

435 440 445

Gly Glu Lys Tyr Asp Pro Asp Ser Ile Leu Tyr Leu Cys Leu Gly Ile

450 455 460

Gln Gln Tyr Leu Phe Glu Asn Gly Arg Ile Asp Asn Ile Phe Thr Glu

465 470 475 480

Pro Tyr Ser Arg Phe Met Ile Glu Leu Thr Lys Leu Leu Lys Ile Trp

485 490 495

Glu Pro Thr Ile Leu Pro Asn Gly Tyr Met Phe Ser Arg Ile Glu Glu

500 505 510

Glu His Leu Trp Glu Cys Lys Gln Leu Gly Ala Tyr Ser Pro Ile Val

515 520 525

Leu Leu Asn Thr Leu Leu Phe Phe Asn Thr Lys Tyr Phe Gln Leu Lys

530 535 540

Asn Val Thr Glu His Leu Lys Leu Ser Phe Ala His Val Met Arg Arg

545 550 555 560

Thr Arg Thr Leu Lys Tyr Ser Thr Lys Met Thr Tyr Leu Arg Phe Phe

565 570 575

Pro Pro Leu Gln Lys Gln Glu Ser Glu Pro Asp Lys Leu Thr Val Gly

580 585 590

Lys Arg Lys Arg Asn Glu Asp Asp Glu Val Pro Val Gly Val Glu Met

595 600 605

Ala Glu Asn Thr Asp Asn Pro Leu Arg Cys Pro Val Arg Leu Tyr Glu

610 615 620

Phe Tyr Leu Ser Lys Cys Ser Glu Ser Val Lys Gln Arg Asn Asp Val

625 630 635 640

Phe Tyr Leu Gln Pro Glu Arg Ser Cys Val Pro Asn Ser Pro Met Trp

645 650 655

Tyr Ser Ala Phe Pro Ile Asp Pro Gly Thr Leu Asp Thr Met Leu Thr

660 665 670

Arg Ile Leu Met Val Arg Glu Val His Glu Glu Leu Ala Lys Ala Lys

675 680 685

Ser Glu Asp Ser Asp Val Glu Leu Ser Asp

690 695

<210> SEQ ID NO 17

<211> LENGTH: 2142

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 17

atgaaacatt tctgtaacct gctttgtatc ttgatgttct gtaatcagca aagtgtatgt 60

gacccgcctt cacaaaataa tgcagcaaat atttccatgg ttcaagctgc ttcagcagga 120

cccccatctc tgagaaaaga ttcgactcca gttatagcca atgtagtatc attggcaagt 180

gcccctgctg ctcagcctac agtgaattct aacagtgtct tacaaggtgc agttccaaca 240

gtaacagcga aaatcatcgg tgatgcaagt actcaaacag atgccctgaa actgccacct 300

tcccaacctc caaggctttt gaagaacaaa gctttattat gcaaacccat cacacagact 360

aaagccacct cttgcaaacc acatacccaa aacaaagaat gccagacaga agacactcca 420

agtcagcccc agattattgt ggtgccagtt cccgtaccag tgtttgttcc catacctctt 480

cacctttata ctcaatatgc tccagtccca tttggaattc cagttccaat gcctgtccct 540

atgcttattc catcttcaat ggatagtgaa gataaagtca cagagagtat tgaagacatt 600

aaagaaaagc ttcccacaca tccatttgaa gctgatctcc ttgagatggc agaaatgatt 660

gcagaagatg aagagaagaa gactctatct cagggagagt cccaaacttc tgaacacgaa 720

ctctttctag acaccaagat atttgaaaaa gaccaaggaa gtacatacag tggtgatctt 780

gaatcagagg cagtatctac tctacatagc tgggaggaag agctgaatca ctatgcctta 840

aagtcaaatg ctgtgcaaga ggctgattca gaattgaagc agttctcaaa aggggaaact 900

gaacaggacc tggaagcaga ttttccatca gactcctttg acccacttaa taaaggacag 960

ggaatccagg cacgttcccg aacaagacga cgacacagag atggcttccc ccaacccaga 1020

cgaagaggac ggaagaagtc tatagtggct gtggagccca ggagtcttat tcaaggagcc 1080

tttcaaggct gctcagtgtc cgggatgaca ctgaaataca tgtatggggt aaatgcttgg 1140

aagaactggg ttcagtggaa aaatgccaag gaagagcagg gggatctaaa atgtggaggg 1200

gttgaacagg cctcatctag cccacgttct gaccccttag gaagtactca agaccatgca 1260

ctctctcaag aatcctcaga gccaggctgt agagtccgct ctatcaagct gaaggaagac 1320

attctgtcct gcacttttgc tgagttgagt ttgggcttat gccagtttat ccaagaggtg 1380

cggagaccaa atggtgaaaa atatgatcca gacagtatct tatacttgtg ccttggaatt 1440

caacagtacc tgtttgaaaa tggtagaata gataacattt ttactgagcc ctattccaga 1500

tttatgattg aacttaccaa actcttgaaa atatgggaac ctacaatact tcctaatggt 1560

tacatgttct ctcgcattga ggaagagcat ttgtgggagt gcaaacagct gggcgcttac 1620

tcaccaatcg tccttttaaa caccctcctt ttcttcaata ccaaatactt ccaactaaag 1680

aatgttactg agcacttgaa gctttccttt gcccatgtga tgagacggac caggactctg 1740

aagtacagta ccaagatgac atatctgagg ttcttcccac ctttacagaa gcaggagtca 1800

gaaccagata aactgactgt tggcaagagg aaacgaaatg aagatgatga ggttccagtg 1860

ggggtggaga tggcagagaa tactgacaat ccactaagat gcccagtccg actttatgag 1920

ttttacctgt caaaatgttc tgaaagtgtg aagcaaagga atgatgtgtt ttaccttcaa 1980

cctgagcgct cctgtgtccc gaatagcccc atgtggtact ccgcattccc gatagaccct 2040

ggaaccctgg acaccatgtt aacacgtatt ctcatggtga gggaggtaca tgaagaactt 2100

gccaaagcca aatctgaaga ctctgatgtt gaattatcag at 2142

<210> SEQ ID NO 18

<211> LENGTH: 2662

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<220> FEATURE:

<221> NAME/KEY: sig_peptide

<222> LOCATION: (6)..(53)

<221> NAME/KEY: mat_peptide

<222> LOCATION: (54)..(2147)

<221> NAME/KEY: CDS

<222> LOCATION: (6)..(2147)

<400> SEQUENCE: 18

gggaa atg aaa cat ttc tgt aac ctg ctt tgt atc ttg atg ttc tgt aat 50

Met Lys His Phe Cys Asn Leu Leu Cys Ile Leu Met Phe Cys Asn

-15 -10 -5

cag caa agt gta tgt gac ccg cct tca caa aat aat gca gca aat att 98

Gln Gln Ser Val Cys Asp Pro Pro Ser Gln Asn Asn Ala Ala Asn Ile

-1 1 5 10 15

tcc atg gtt caa gct gct tca gca gga ccc cca tct ctg aga aaa gat 146

Ser Met Val Gln Ala Ala Ser Ala Gly Pro Pro Ser Leu Arg Lys Asp

20 25 30

tcg act cca gtt ata gcc aat gta gta tca ttg gca agt gcc cct gct 194

Ser Thr Pro Val Ile Ala Asn Val Val Ser Leu Ala Ser Ala Pro Ala

35 40 45

gct cag cct aca gtg aat tct aac agt gtc tta caa ggt gca gtt cca 242

Ala Gln Pro Thr Val Asn Ser Asn Ser Val Leu Gln Gly Ala Val Pro

50 55 60

aca gta aca gcg aaa atc atc ggt gat gca agt act caa aca gat gcc 290

Thr Val Thr Ala Lys Ile Ile Gly Asp Ala Ser Thr Gln Thr Asp Ala

65 70 75

ctg aaa ctg cca cct tcc caa cct cca agg ctt ttg aag aac aaa gct 338

Leu Lys Leu Pro Pro Ser Gln Pro Pro Arg Leu Leu Lys Asn Lys Ala

80 85 90 95

tta tta tgc aaa ccc atc aca cag act aaa gcc acc tct tgc aaa cca 386

Leu Leu Cys Lys Pro Ile Thr Gln Thr Lys Ala Thr Ser Cys Lys Pro

100 105 110

cat acc caa aac aaa gaa tgc cag aca gaa gac act cca agt cag ccc 434

His Thr Gln Asn Lys Glu Cys Gln Thr Glu Asp Thr Pro Ser Gln Pro

115 120 125

cag att att gtg gtg cca gtt ccc gta cca gtg ttt gtt ccc ata cct 482

Gln Ile Ile Val Val Pro Val Pro Val Pro Val Phe Val Pro Ile Pro

130 135 140

ctt cac ctt tat act caa tat gct cca gtc cca ttt gga att cca gtt 530

Leu His Leu Tyr Thr Gln Tyr Ala Pro Val Pro Phe Gly Ile Pro Val

145 150 155

cca atg cct gtc cct atg ctt att cca tct tca atg gat agt gaa gat 578

Pro Met Pro Val Pro Met Leu Ile Pro Ser Ser Met Asp Ser Glu Asp

160 165 170 175

aaa gtc aca gag agt att gaa gac att aaa gaa aag ctt ccc aca cat 626

Lys Val Thr Glu Ser Ile Glu Asp Ile Lys Glu Lys Leu Pro Thr His

180 185 190

cca ttt gaa gct gat ctc ctt gag atg gca gaa atg att gca gaa gat 674

Pro Phe Glu Ala Asp Leu Leu Glu Met Ala Glu Met Ile Ala Glu Asp

195 200 205

gaa gag aag aag act cta tct cag gga gag tcc caa act tct gaa cac 722

Glu Glu Lys Lys Thr Leu Ser Gln Gly Glu Ser Gln Thr Ser Glu His

210 215 220

gaa ctc ttt cta gac acc aag ata ttt gaa aaa gac caa gga agt aca 770

Glu Leu Phe Leu Asp Thr Lys Ile Phe Glu Lys Asp Gln Gly Ser Thr

225 230 235

tac agt ggt gat ctt gaa tca gag gca gta tct act cta cat agc tgg 818

Tyr Ser Gly Asp Leu Glu Ser Glu Ala Val Ser Thr Leu His Ser Trp

240 245 250 255

gag gaa gag ctg aat cac tat gcc tta aag tca aat gct gtg caa gag 866

Glu Glu Glu Leu Asn His Tyr Ala Leu Lys Ser Asn Ala Val Gln Glu

260 265 270

gct gat tca gaa ttg aag cag ttc tca aaa ggg gaa act gaa cag gac 914

Ala Asp Ser Glu Leu Lys Gln Phe Ser Lys Gly Glu Thr Glu Gln Asp

275 280 285

ctg gaa gca gat ttt cca tca gac tcc ttt gac cca ctt aat aaa gga 962

Leu Glu Ala Asp Phe Pro Ser Asp Ser Phe Asp Pro Leu Asn Lys Gly

290 295 300

cag gga atc cag gca cgt tcc cga aca aga cga cga cac aga gat ggc 1010

Gln Gly Ile Gln Ala Arg Ser Arg Thr Arg Arg Arg His Arg Asp Gly

305 310 315

ttc ccc caa ccc aga cga aga gga cgg aag aag tct ata gtg gct gtg 1058

Phe Pro Gln Pro Arg Arg Arg Gly Arg Lys Lys Ser Ile Val Ala Val

320 325 330 335

gag ccc agg agt ctt att caa gga gcc ttt caa ggc tgc tca gtg tcc 1106

Glu Pro Arg Ser Leu Ile Gln Gly Ala Phe Gln Gly Cys Ser Val Ser

340 345 350

ggg atg aca ctg aaa tac atg tat ggg gta aat gct tgg aag aac tgg 1154

Gly Met Thr Leu Lys Tyr Met Tyr Gly Val Asn Ala Trp Lys Asn Trp

355 360 365

gtt cag tgg aaa aat gcc aag gaa gag cag ggg gat cta aaa tgt gga 1202

Val Gln Trp Lys Asn Ala Lys Glu Glu Gln Gly Asp Leu Lys Cys Gly

370 375 380

ggg gtt gaa cag gcc tca tct agc cca cgt tct gac ccc tta gga agt 1250

Gly Val Glu Gln Ala Ser Ser Ser Pro Arg Ser Asp Pro Leu Gly Ser

385 390 395

act caa gac cat gca ctc tct caa gaa tcc tca gag cca ggc tgt aga 1298

Thr Gln Asp His Ala Leu Ser Gln Glu Ser Ser Glu Pro Gly Cys Arg

400 405 410 415

gtc cgc tct atc aag ctg aag gaa gac att ctg tcc tgc act ttt gct 1346

Val Arg Ser Ile Lys Leu Lys Glu Asp Ile Leu Ser Cys Thr Phe Ala

420 425 430

gag ttg agt ttg ggc tta tgc cag ttt atc caa gag gtg cgg aga cca 1394

Glu Leu Ser Leu Gly Leu Cys Gln Phe Ile Gln Glu Val Arg Arg Pro

435 440 445

aat ggt gaa aaa tat gat cca gac agt atc tta tac ttg tgc ctt gga 1442

Asn Gly Glu Lys Tyr Asp Pro Asp Ser Ile Leu Tyr Leu Cys Leu Gly

450 455 460

att caa cag tac ctg ttt gaa aat ggt aga ata gat aac att ttt act 1490

Ile Gln Gln Tyr Leu Phe Glu Asn Gly Arg Ile Asp Asn Ile Phe Thr

465 470 475

gag ccc tat tcc aga ttt atg att gaa ctt acc aaa ctc ttg aaa ata 1538

Glu Pro Tyr Ser Arg Phe Met Ile Glu Leu Thr Lys Leu Leu Lys Ile

480 485 490 495

tgg gaa cct aca ata ctt cct aat ggt tac atg ttc tct cgc att gag 1586

Trp Glu Pro Thr Ile Leu Pro Asn Gly Tyr Met Phe Ser Arg Ile Glu

500 505 510

gaa gag cat ttg tgg gag tgc aaa cag ctg ggc gct tac tca cca atc 1634

Glu Glu His Leu Trp Glu Cys Lys Gln Leu Gly Ala Tyr Ser Pro Ile

515 520 525

gtc ctt tta aac acc ctc ctt ttc ttc aat acc aaa tac ttc caa cta 1682

Val Leu Leu Asn Thr Leu Leu Phe Phe Asn Thr Lys Tyr Phe Gln Leu

530 535 540

aag aat gtt act gag cac ttg aag ctt tcc ttt gcc cat gtg atg aga 1730

Lys Asn Val Thr Glu His Leu Lys Leu Ser Phe Ala His Val Met Arg

545 550 555

cgg acc agg act ctg aag tac agt acc aag atg aca tat ctg agg ttc 1778

Arg Thr Arg Thr Leu Lys Tyr Ser Thr Lys Met Thr Tyr Leu Arg Phe

560 565 570 575

ttc cca cct tta cag aag cag gag tca gaa cca gat aaa ctg act gtt 1826

Phe Pro Pro Leu Gln Lys Gln Glu Ser Glu Pro Asp Lys Leu Thr Val

580 585 590

ggc aag agg aaa cga aat gaa gat gat gag gtt cca gtg ggg gtg gag 1874

Gly Lys Arg Lys Arg Asn Glu Asp Asp Glu Val Pro Val Gly Val Glu

595 600 605

atg gca gag aat act gac aat cca cta aga tgc cca gtc cga ctt tat 1922

Met Ala Glu Asn Thr Asp Asn Pro Leu Arg Cys Pro Val Arg Leu Tyr

610 615 620

gag ttt tac ctg tca aaa tgt tct gaa agt gtg aag caa agg aat gat 1970

Glu Phe Tyr Leu Ser Lys Cys Ser Glu Ser Val Lys Gln Arg Asn Asp

625 630 635

gtg ttt tac ctt caa cct gag cgc tcc tgt gtc ccg aat agc ccc atg 2018

Val Phe Tyr Leu Gln Pro Glu Arg Ser Cys Val Pro Asn Ser Pro Met

640 645 650 655

tgg tac tcc gca ttc ccg ata gac cct gga acc ctg gac acc atg tta 2066

Trp Tyr Ser Ala Phe Pro Ile Asp Pro Gly Thr Leu Asp Thr Met Leu

660 665 670

aca cgt att ctc atg gtg agg gag gta cat gaa gaa ctt gcc aaa gcc 2114

Thr Arg Ile Leu Met Val Arg Glu Val His Glu Glu Leu Ala Lys Ala

675 680 685

aaa tct gaa gac tct gat gtt gaa tta tca gat taaaacggaa gtgaggttct 2167

Lys Ser Glu Asp Ser Asp Val Glu Leu Ser Asp

690 695

tattttcata catattggta tgcaccaaac tgtgaatgca tccagctgtt ggaaaatgat 2227

gtataagtct aagtcctctt gacttgacca taagatcatg gaaaacagat gacttgtgaa 2287

ccccacagtg tggatgtgca aatgaaaatt gaaggaaaga atatgaactg agaaatgttc 2347

tttggcagtg atatagttct tagacatctt cagaatgact aatttctccg agtggtgcat 2407

aatcttattt tgtttgggag taacaaatcg tggaatattt ttaaggaaaa ctgttgtata 2467

aaactttacc atagtaacct tagaccttag agaggtagct ttggagtgaa actttggctg 2527

caataggcta ctttggcaag ccctccgtaa aagtcagagg agagatcagt acagagctaa 2587

gagtgacatc aaatgaggac tgtgggaccc agatttgaag acccaataaa aatactcaac 2647

tttttaaaaa aaaaa 2662

210> SEQ ID NO 19

<211> LENGTH: 81

<212> TYPE: PRT

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 19

Met Arg Thr Tyr His Tyr Ile Pro Leu Phe Ile Trp Thr Tyr Met Phe

-20 -15 -10

His Thr Val Asp Thr Ile Leu Leu Gln Glu Lys Pro Asn Ser Tyr Leu

-5 -1 1 5

Ser Ser Lys Lys Ile Ala Gly Leu Thr Lys Asp Asp Gly Lys Met Leu

10 15 20

Arg Arg Thr Lys Arg Gly Trp Met Trp Asn Gln Phe Phe Leu Leu Glu

25 30 35 40

Glu Tyr Thr Gly Thr Asp Thr Gln Tyr Val Gly Lys Val Arg Ile Phe

45 50 55

Val

<210> SEQ ID NO 20

<211> LENGTH: 243

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 20

atgaggactt accattatat accattattc atctggacct atatgttcca tacagttgac 60

accatcctat tacaagaaaa acctaacagt tatttatcaa gcaaaaagat agcgggtctg 120

acaaaagatg acggtaaaat gctacgtcgc accaagcgtg gctggatgtg gaatcagttc 180

ttcttattgg aagagtacac aggtactgac acacaatatg taggcaaggt aagaattttt 240

gta 243

<210> SEQ ID NO 21

<211> LENGTH: 630

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<220> FEATURE:

<221> NAME/KEY: sig_peptide

<222> LOCATION: (160)..(231)

<221> NAME/KEY: mat_peptide

<222> LOCATION: (232)..(402)

<221> NAME/KEY: CDS

<222> LOCATION: (160)..(402)

<400> SEQUENCE: 21

aagatcagct gtgaagatac tataaaaagg gaagagaagg accgagacag aagcaacaac 60

ggaactgtca gtgcggagta gggctaaact cagttccatt gttaagcaag gaaaaacaaa 120

caatacattg aatttgacaa cccactgaag ttgcagata atg agg act tac cat 174

Met Arg Thr Tyr His

-20

tat ata cca tta ttc atc tgg acc tat atg ttc cat aca gtt gac acc 222

Tyr Ile Pro Leu Phe Ile Trp Thr Tyr Met Phe His Thr Val Asp Thr

-15 -10 -5

atc cta tta caa gaa aaa cct aac agt tat tta tca agc aaa aag ata 270

Ile Leu Leu Gln Glu Lys Pro Asn Ser Tyr Leu Ser Ser Lys Lys Ile

-1 1 5 10

gcg ggt ctg aca aaa gat gac ggt aaa atg cta cgt cgc acc aag cgt 318

Ala Gly Leu Thr Lys Asp Asp Gly Lys Met Leu Arg Arg Thr Lys Arg

15 20 25

ggc tgg atg tgg aat cag ttc ttc tta ttg gaa gag tac aca ggt act 366

Gly Trp Met Trp Asn Gln Phe Phe Leu Leu Glu Glu Tyr Thr Gly Thr

30 35 40 45

gac aca caa tat gta ggc aag gta aga att ttt gta tgagaaatct 412

Asp Thr Gln Tyr Val Gly Lys Val Arg Ile Phe Val

50 55

aaaagctgaa agtgacagct atttattttt ttccagcaac ttttcttttc actagtgatt 472

attaaaaaat atttaactaa ttatgttctg aaggtgtgat attgcaaact attttagtgg 532

ggaagaacaa ggaaccatat ttgggttcta aatgtaaatc aatgtcaata ataagcgtaa 592

gctactaagt catatgtgga tggatgtgat cattatta 630

<210> SEQ ID NO 22

<211> LENGTH: 150

<212> TYPE: PRT

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 22

Met Arg Lys Thr Arg Leu Trp Gly Leu Leu Trp Met Leu Phe Val Ser

-20 -15 -10 -5

Glu Leu Arg Ala Ala Thr Lys Leu Thr Glu Glu Lys Tyr Glu Leu Lys

-1 1 5 10

Glu Gly Gln Thr Leu Asp Val Lys Cys Asp Tyr Thr Leu Glu Lys Phe

15 20 25

Ala Ser Ser Gln Lys Ala Trp Gln Ile Ile Arg Asp Gly Glu Met Pro

30 35 40

Lys Thr Leu Ala Cys Thr Glu Arg Pro Ser Lys Asn Ser His Pro Val

45 50 55 60

Gln Val Gly Arg Ile Ile Leu Glu Asp Tyr His Asp His Gly Leu Leu

65 70 75

Arg Val Arg Met Val Asn Leu Gln Val Glu Asp Ser Gly Leu Tyr Gln

80 85 90

Cys Val Ile Tyr Gln Pro Pro Lys Glu Pro His Met Leu Phe Asp Arg

95 100 105

Ile Arg Leu Val Val Thr Lys Gly Phe Arg Cys Ser Thr Leu Ser Phe

110 115 120

Ser Trp Leu Val Asp Ser

125 130

<210> SEQ ID NO 23

<211> LENGTH: 450

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 23

atgaggaaga ccaggctctg ggggctgctg tggatgctct ttgtctcaga actccgagct 60

gcaactaaat taactgagga aaagtatgaa ctgaaagagg ggcagaccct ggatgtgaaa 120

tgtgactaca cgctagagaa gtttgccagc agccagaaag cttggcagat aataagggac 180

ggagagatgc ccaagaccct ggcatgcaca gagaggcctt caaagaattc ccatccagtc 240

caagtgggga ggatcatact agaagactac catgatcatg gtttactgcg cgtccgaatg 300

gtcaaccttc aagtggaaga ttctggactg tatcagtgtg tgatctacca gcctcccaag 360

gagcctcaca tgctgttcga tcgcatccgc ttggtggtga ccaaggggtt ccggtgttca 420

acattgtcat tctcctggct ggtggattcc 450

<210> SEQ ID NO 24

<211> LENGTH: 701

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<220> FEATURE:

<221> NAME/KEY: sig_peptide

<222> LOCATION: (19)..(78)

<221> NAME/KEY: mat_peptide

<222> LOCATION: (79)..(468)

<221> NAME/KEY: CDS

<222> LOCATION: (19)..(468)

<400> SEQUENCE: 24

agctggtgca caggaagg atg agg aag acc agg ctc tgg ggg ctg ctg tgg 51

Met Arg Lys Thr Arg Leu Trp Gly Leu Leu Trp

-20 -15 -10

atg ctc ttt gtc tca gaa ctc cga gct gca act aaa tta act gag gaa 99

Met Leu Phe Val Ser Glu Leu Arg Ala Ala Thr Lys Leu Thr Glu Glu

-5 -1 1 5

aag tat gaa ctg aaa gag ggg cag acc ctg gat gtg aaa tgt gac tac 147

Lys Tyr Glu Leu Lys Glu Gly Gln Thr Leu Asp Val Lys Cys Asp Tyr

10 15 20

acg cta gag aag ttt gcc agc agc cag aaa gct tgg cag ata ata agg 195

Thr Leu Glu Lys Phe Ala Ser Ser Gln Lys Ala Trp Gln Ile Ile Arg

25 30 35

gac gga gag atg ccc aag acc ctg gca tgc aca gag agg cct tca aag 243

Asp Gly Glu Met Pro Lys Thr Leu Ala Cys Thr Glu Arg Pro Ser Lys

40 45 50 55

aat tcc cat cca gtc caa gtg ggg agg atc ata cta gaa gac tac cat 291

Asn Ser His Pro Val Gln Val Gly Arg Ile Ile Leu Glu Asp Tyr His

60 65 70

gat cat ggt tta ctg cgc gtc cga atg gtc aac ctt caa gtg gaa gat 339

Asp His Gly Leu Leu Arg Val Arg Met Val Asn Leu Gln Val Glu Asp

75 80 85

tct gga ctg tat cag tgt gtg atc tac cag cct ccc aag gag cct cac 387

Ser Gly Leu Tyr Gln Cys Val Ile Tyr Gln Pro Pro Lys Glu Pro His

90 95 100

atg ctg ttc gat cgc atc cgc ttg gtg gtg acc aag ggg ttc cgg tgt 435

Met Leu Phe Asp Arg Ile Arg Leu Val Val Thr Lys Gly Phe Arg Cys

105 110 115

tca aca ttg tca ttc tcc tgg ctg gtg gat tcc tgagtaagag cctggtcttc 488

Ser Thr Leu Ser Phe Ser Trp Leu Val Asp Ser

120 125 130

tctgtcctgt ttgctgtcac gctgaggtca tttgtaccct aggcccacga acccacgaga 548

atgtcctctg acttccagcc acatccatct ggcagttgtg ccaagggagg agggaggagg 608

taaaaggcag ggagttaata acatgaatta aatctgtaat caccagctaa agaaaaaaaa 668

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaa 701

<210> SEQ ID NO 25

<211> LENGTH: 422

<212> TYPE: PRT

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 25

Met Leu Gln Trp Arg Arg Arg His Cys Cys Phe Ala Lys Met Thr Trp

-35 -30 -25

Asn Ala Lys Arg Ser Leu Phe Arg Thr His Leu Ile Gly Val Leu Ser

-20 -15 -10

Leu Val Phe Leu Phe Ala Met Phe Leu Phe Phe Asn His His Asp Trp

-5 -1 1 5 10

Leu Pro Gly Arg Ala Gly Phe Lys Glu Asn Pro Val Thr Tyr Thr Phe

15 20 25

Arg Gly Phe Arg Ser Thr Lys Ser Glu Thr Asn His Ser Ser Leu Arg

30 35 40

Asn Ile Trp Lys Glu Thr Val Pro Gln Thr Leu Arg Pro Gln Thr Ala

45 50 55

Thr Asn Ser Asn Asn Thr Asp Leu Ser Pro Gln Gly Val Thr Gly Leu

60 65 70

Glu Asn Thr Leu Ser Ala Asn Gly Ser Ile Tyr Asn Glu Lys Gly Thr

75 80 85 90

Gly His Pro Asn Ser Tyr His Phe Lys Tyr Ile Ile Asn Glu Pro Glu

95 100 105

Lys Cys Gln Glu Lys Ser Pro Phe Leu Ile Leu Leu Ile Ala Ala Glu

110 115 120

Pro Gly Gln Ile Glu Ala Arg Arg Ala Ile Arg Gln Thr Trp Gly Asn

125 130 135

Glu Ser Leu Ala Pro Gly Ile Gln Ile Thr Arg Ile Phe Leu Leu Gly

140 145 150

Leu Ser Ile Lys Leu Asn Gly Tyr Leu Gln Arg Ala Ile Leu Glu Glu

155 160 165 170

Ser Arg Gln Tyr His Asp Ile Ile Gln Gln Glu Tyr Leu Asp Thr Tyr

175 180 185

Tyr Asn Leu Thr Ile Lys Thr Leu Met Gly Met Asn Trp Val Ala Thr

190 195 200

Tyr Cys Pro His Ile Pro Tyr Val Met Lys Thr Asp Ser Asp Met Phe

205 210 215

Val Asn Thr Glu Tyr Leu Ile Asn Lys Leu Leu Lys Pro Asp Leu Pro

220 225 230

Pro Arg His Asn Tyr Phe Thr Gly Tyr Leu Met Arg Gly Tyr Ala Pro

235 240 245 250

Asn Arg Asn Lys Asp Ser Lys Trp Tyr Met Pro Pro Asp Leu Tyr Pro

255 260 265

Ser Glu Arg Tyr Pro Val Phe Cys Ser Gly Thr Gly Tyr Val Phe Ser

270 275 280

Gly Asp Leu Ala Glu Lys Ile Phe Lys Val Ser Leu Gly Ile Arg Arg

285 290 295

Leu His Leu Glu Asp Val Tyr Val Gly Ile Cys Leu Ala Lys Leu Arg

300 305 310

Ile Asp Pro Val Pro Pro Pro Asn Glu Phe Val Phe Asn His Trp Arg

315 320 325 330

Val Ser Tyr Ser Ser Cys Lys Tyr Ser His Leu Ile Thr Ser His Gln

335 340 345

Phe Gln Pro Ser Glu Leu Ile Lys Tyr Trp Asn His Leu Gln Gln Asn

350 355 360

Lys His Asn Ala Cys Ala Asn Ala Ala Lys Glu Lys Ala Gly Arg Tyr

365 370 375

Arg His Arg Lys Leu His

380

<210> SEQ ID NO 26

<211> LENGTH: 1266

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 26

atgcttcagt ggaggagaag acactgctgc tttgcaaaga tgacctggaa tgccaaaagg 60

tctctgttcc gcactcatct tattggagta ctttctctag tgtttctttt tgctatgttt 120

ttgtttttca atcatcatga ctggctgcca ggcagagctg gattcaaaga aaaccctgtg 180

acatacactt tccgaggatt tcggtcaaca aaaagtgaga caaaccacag ctcccttcgg 240

aacatttgga aagaaacagt ccctcaaacc ctgaggcctc aaacagcaac taactctaat 300

aacacagacc tgtcaccaca aggagttaca ggcctggaga atacacttag tgccaatgga 360

agtatttaca atgaaaaagg tactggacat ccaaattctt accatttcaa atatattatt 420

aatgagcctg aaaaatgcca agagaaaagt ccttttttaa tactactaat agctgcagag 480

cctggacaaa tagaagctag aagagctatt cggcaaactt ggggcaatga aagtctagca 540

cctggtattc aaatcacaag aatatttttg ttgggcttaa gtattaagct aaatggctac 600

cttcaacgtg caatactgga agaaagcaga caatatcatg atataattca acaggaatac 660

ttagatacgt actataattt gaccattaaa acactaatgg gcatgaactg ggttgcaaca 720

tactgtccac atattccata tgttatgaaa actgacagtg acatgtttgt caacactgaa 780

tatttaatca ataagttact gaagccagat ctgcctccca gacataacta tttcactggt 840

tacctaatgc gaggatatgc acccaatcga aacaaagata gcaagtggta catgccacca 900

gacctctacc caagtgagcg ttatcctgtc ttctgttctg gaactggtta tgttttttct 960

ggagatctgg cagaaaagat ttttaaagtt tctttaggta tccgccgttt gcacttggaa 1020

gatgtatatg tagggatctg tcttgccaag ttgagaattg atcctgtacc ccctcccaat 1080

gagtttgtgt tcaatcactg gcgagtctct tattcgagct gtaaatacag ccacctaatt 1140

acctctcatc agttccagcc tagtgaactg ataaaatact ggaaccattt acaacaaaat 1200

aagcacaatg cctgtgccaa cgcagcaaaa gaaaaggcag gcaggtatcg ccaccgtaaa 1260

ctacat 1266

<210> SEQ ID NO 27

<211> LENGTH: 2420

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<220> FEATURE:

<221> NAME/KEY: sig_peptide

<222> LOCATION: (698)..(811)

<221> NAME/KEY: mat_peptide

<222> LOCATION: (812)..(1963)

<221> NAME/KEY: CDS

<222> LOCATION: (698)..(1963)

<400> SEQUENCE: 27

gcctgtgcag cagctgagga accgtggatt tcatattata gactaaaacc ccattaaaac 60

tgctcaaaat ccttcctgca gctgccaggc aacaacgaaa gaagagaggt aaatcctatt 120

cttttccaat acaactgaag cactacattt tagctctggc tgctttacat tgcagctcag 180

tgttattagt agaaatatgg atactgagac gagaacacag cactgcattg tccagccagg 240

aaaatagcag atgtaaaaag cttcaatgca tcaactgtcg ggaagagtca acagtgctac 300

aagcagaacg ggcaactaca gctcttttgt ttaacgaaag agagaaaatg aaagaaaggg 360

aaaatttcag aagactagga cccatatgaa caaggagggt aactcgaaga caagcagaca 420

gatggacact ttggatactg tgaaaagcaa tcgcaggagg cagactgttg ggggatgtgc 480

gcatgttcga tagcatcttt tttgctgaag tgatggcgtg ccaaaagtat tttcagtggg 540

cataatcctc ttcacataaa tggcctgacc aaggaagaat gactacaaga gagacaatgt 600

gactgaatta gaaaatgatt gccaaagaat agtattaagg agaagaaaac atttttggtc 660

accaatctct catataccac tactggatat ttacaac atg ctt cag tgg agg aga 715

Met Leu Gln Trp Arg Arg

-35

aga cac tgc tgc ttt gca aag atg acc tgg aat gcc aaa agg tct ctg 763

Arg His Cys Cys Phe Ala Lys Met Thr Trp Asn Ala Lys Arg Ser Leu

-30 -25 -20

ttc cgc act cat ctt att gga gta ctt tct cta gtg ttt ctt ttt gct 811

Phe Arg Thr His Leu Ile Gly Val Leu Ser Leu Val Phe Leu Phe Ala

-15 -10 -5 -1

atg ttt ttg ttt ttc aat cat cat gac tgg ctg cca ggc aga gct gga 859

Met Phe Leu Phe Phe Asn His His Asp Trp Leu Pro Gly Arg Ala Gly

1 5 10 15

ttc aaa gaa aac cct gtg aca tac act ttc cga gga ttt cgg tca aca 907

Phe Lys Glu Asn Pro Val Thr Tyr Thr Phe Arg Gly Phe Arg Ser Thr

20 25 30

aaa agt gag aca aac cac agc tcc ctt cgg aac att tgg aaa gaa aca 955

Lys Ser Glu Thr Asn His Ser Ser Leu Arg Asn Ile Trp Lys Glu Thr

35 40 45

gtc cct caa acc ctg agg cct caa aca gca act aac tct aat aac aca 1003

Val Pro Gln Thr Leu Arg Pro Gln Thr Ala Thr Asn Ser Asn Asn Thr

50 55 60

gac ctg tca cca caa gga gtt aca ggc ctg gag aat aca ctt agt gcc 1051

Asp Leu Ser Pro Gln Gly Val Thr Gly Leu Glu Asn Thr Leu Ser Ala

65 70 75 80

aat gga agt att tac aat gaa aaa ggt act gga cat cca aat tct tac 1099

Asn Gly Ser Ile Tyr Asn Glu Lys Gly Thr Gly His Pro Asn Ser Tyr

85 90 95

cat ttc aaa tat att att aat gag cct gaa aaa tgc caa gag aaa agt 1147

His Phe Lys Tyr Ile Ile Asn Glu Pro Glu Lys Cys Gln Glu Lys Ser

100 105 110

cct ttt tta ata cta cta ata gct gca gag cct gga caa ata gaa gct 1195

Pro Phe Leu Ile Leu Leu Ile Ala Ala Glu Pro Gly Gln Ile Glu Ala

115 120 125

aga aga gct att cgg caa act tgg ggc aat gaa agt cta gca cct ggt 1243

Arg Arg Ala Ile Arg Gln Thr Trp Gly Asn Glu Ser Leu Ala Pro Gly

130 135 140

att caa atc aca aga ata ttt ttg ttg ggc tta agt att aag cta aat 1291

Ile Gln Ile Thr Arg Ile Phe Leu Leu Gly Leu Ser Ile Lys Leu Asn

145 150 155 160

ggc tac ctt caa cgt gca ata ctg gaa gaa agc aga caa tat cat gat 1339

Gly Tyr Leu Gln Arg Ala Ile Leu Glu Glu Ser Arg Gln Tyr His Asp

165 170 175

ata att caa cag gaa tac tta gat acg tac tat aat ttg acc att aaa 1387

Ile Ile Gln Gln Glu Tyr Leu Asp Thr Tyr Tyr Asn Leu Thr Ile Lys

180 185 190

aca cta atg ggc atg aac tgg gtt gca aca tac tgt cca cat att cca 1435

Thr Leu Met Gly Met Asn Trp Val Ala Thr Tyr Cys Pro His Ile Pro

195 200 205

tat gtt atg aaa act gac agt gac atg ttt gtc aac act gaa tat tta 1483

Tyr Val Met Lys Thr Asp Ser Asp Met Phe Val Asn Thr Glu Tyr Leu

210 215 220

atc aat aag tta ctg aag cca gat ctg cct ccc aga cat aac tat ttc 1531

Ile Asn Lys Leu Leu Lys Pro Asp Leu Pro Pro Arg His Asn Tyr Phe

225 230 235 240

act ggt tac cta atg cga gga tat gca ccc aat cga aac aaa gat agc 1579

Thr Gly Tyr Leu Met Arg Gly Tyr Ala Pro Asn Arg Asn Lys Asp Ser

245 250 255

aag tgg tac atg cca cca gac ctc tac cca agt gag cgt tat cct gtc 1627

Lys Trp Tyr Met Pro Pro Asp Leu Tyr Pro Ser Glu Arg Tyr Pro Val

260 265 270

ttc tgt tct gga act ggt tat gtt ttt tct gga gat ctg gca gaa aag 1675

Phe Cys Ser Gly Thr Gly Tyr Val Phe Ser Gly Asp Leu Ala Glu Lys

275 280 285

att ttt aaa gtt tct tta ggt atc cgc cgt ttg cac ttg gaa gat gta 1723

Ile Phe Lys Val Ser Leu Gly Ile Arg Arg Leu His Leu Glu Asp Val

290 295 300

tat gta ggg atc tgt ctt gcc aag ttg aga att gat cct gta ccc cct 1771

Tyr Val Gly Ile Cys Leu Ala Lys Leu Arg Ile Asp Pro Val Pro Pro

305 310 315 320

ccc aat gag ttt gtg ttc aat cac tgg cga gtc tct tat tcg agc tgt 1819

Pro Asn Glu Phe Val Phe Asn His Trp Arg Val Ser Tyr Ser Ser Cys

325 330 335

aaa tac agc cac cta att acc tct cat cag ttc cag cct agt gaa ctg 1867

Lys Tyr Ser His Leu Ile Thr Ser His Gln Phe Gln Pro Ser Glu Leu

340 345 350

ata aaa tac tgg aac cat tta caa caa aat aag cac aat gcc tgt gcc 1915

Ile Lys Tyr Trp Asn His Leu Gln Gln Asn Lys His Asn Ala Cys Ala

355 360 365

aac gca gca aaa gaa aag gca ggc agg tat cgc cac cgt aaa cta cat 1963

Asn Ala Ala Lys Glu Lys Ala Gly Arg Tyr Arg His Arg Lys Leu His

370 375 380

tagaaaagac aatttttttt caaatgtgca atttgtaaat attgctaaaa gcatgtatag 2023

ttagaactga ttacatccgt aggacaagtt ttagttaaaa ctcatcacat aaagaaattc 2083

aagaagtatt tttttaattt ctgaagaagt taattcttaa aactataaca ttatataaca 2143

aaaaaggttt cccaaaacaa tctatttaaa aaactgtata aggagattct gtgtattaac 2203

atgcaataac aagcatgcat aaatcaatgg ttcaagtctt ctgttagggg ccaataaaat 2263

gtatctgcat atgttttcca cataaatttt aattcaagaa atgacagtca aaagatcctt 2323

cattttagat taagcttttc attttaatat ataatttaat gtaaataaaa catcactatc 2383

aattttaagg aaaaaaaaaa aaaaaaaaaa aaaaaaa 2420

<210> SEQ ID NO 28

<211> LENGTH: 521

<212> TYPE: PRT

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 28

Met Val Asn Ala Cys Trp Cys Gly Leu Leu Ala Ala Leu Ser Leu Leu

-20 -15 -10

Leu Asp Ala Ser Thr Asp Glu Val Ala Thr Glu Asn Ile Leu Lys Ala

-5 -1 1 5 10

Glu Leu Thr Met Ala Ala Leu Cys Gly Arg Leu Gly Leu Val Thr Ser

15 20 25

Arg Asp Ala Phe Ile Thr Ala Ile Cys Lys Gly Ser Leu Pro Pro His

30 35 40

Tyr Ala Leu Thr Val Leu Asn Thr Thr Thr Ala Ala Thr Leu Ser Asn

45 50 55

Lys Ser Tyr Ser Val Gln Gly Gln Ser Val Met Met Ile Ser Pro Ser

60 65 70 75

Ser Glu Ser His Gln Gln Val Val Ala Val Gly Gln Pro Leu Ala Val

80 85 90

Gln Pro Gln Gly Thr Val Met Leu Thr Ser Lys Asn Ile Gln Cys Met

95 100 105

Arg Thr Leu Leu Asn Leu Ala His Cys His Gly Ala Val Leu Gly Thr

110 115 120

Ser Trp Gln Leu Val Leu Ala Thr Leu Gln His Leu Val Trp Ile Leu

125 130 135

Gly Leu Lys Pro Ser Ser Gly Gly Ala Leu Lys Pro Gly Arg Ala Val

140 145 150 155

Glu Gly Pro Ser Thr Val Leu Thr Thr Ala Val Met Thr Asp Leu Pro

160 165 170

Val Ile Ser Asn Ile Leu Ser Arg Leu Phe Glu Ser Ser Gln Tyr Leu

175 180 185

Asp Asp Val Ser Leu His His Leu Ile Asn Ala Leu Cys Ser Leu Ser

190 195 200

Leu Glu Ala Met Asp Met Ala Tyr Gly Asn Asn Lys Glu Pro Ser Leu

205 210 215

Phe Ala Val Ala Lys Leu Leu Glu Thr Gly Leu Val Asn Met His Arg

220 225 230 235

Ile Glu Ile Leu Trp Arg Pro Leu Thr Gly His Leu Leu Glu Lys Val

240 245 250

Cys Gln His Pro Asn Ser Arg Met Gly Glu Trp Gly Ala Glu Ala Leu

255 260 265

Thr Ser Leu Ile Lys Ala Gly Leu Thr Phe Asn His Asp Pro Pro Leu

270 275 280

Ser Gln Asn Gln Arg Leu Gln Leu Leu Leu Leu Asn Pro Leu Lys Glu

285 290 295

Met Ser Asn Ile Asn His Pro Asp Ile Arg Leu Lys Gln Leu Glu Cys

300 305 310 315

Val Leu Gln Ile Leu Gln Ser Gln Gly Asp Asn Leu Gly Pro Gly Trp

320 325 330

Pro Leu Val Leu Gly Val Met Gly Ala Ile Arg Asn Asp Gln Gly Glu

335 340 345

Ser Leu Ile Arg Thr Ala Phe Gln Cys Leu Gln Leu Val Val Thr Asp

350 355 360

Phe Leu Pro Thr Met Pro Cys Thr Cys Leu Gln Ile Val Val Asp Val

365 370 375

Ala Gly Ser Phe Gly Leu His Asn Gln Glu Leu Asn Ile Ser Leu Thr

380 385 390 395

Ser Ile Gly Leu Leu Trp Asn Ile Ser Asp Tyr Phe Phe Gln Arg Gly

400 405 410

Glu Thr Ile Glu Lys Glu Leu Asn Lys Glu Glu Ala Ala Gln Gln Lys

415 420 425

Gln Ala Glu Glu Lys Gly Val Val Leu Asn Arg Pro Phe His Pro Ala

430 435 440

Pro Pro Phe Asp Cys Leu Trp Leu Cys Leu Tyr Ala Lys Leu Gly Glu

445 450 455

Leu Cys Val Asp Pro Arg Pro Ala Val Arg Lys Ser Ala Gly Gln Thr

460 465 470 475

Leu Phe Ser Thr Ile Gly Ala His Gly Thr Leu Leu Gln His Ser Thr

480 485 490

Trp Arg Thr Val Ile Trp Lys Val Leu

495 500

<210> SEQ ID NO 29

<211> LENGTH: 1563

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 29

atggtgaatg cctgctggtg tggtcttctt gctgcactct cactccttct tgatgccagc 60

acagatgaag ttgccactga gaatatttta aaagctgaac tgactatggc tgctctttgt 120

ggaagactgg gccttgtaac ttcaagagat gcctttataa ctgcaatatg caaaggttcc 180

ctgcctcccc attatgctct tactgtattg aataccacca ctgcagctac actttccaac 240

aaatcatatt ccgttcaggg ccaaagtgtt atgatgataa gtccatcaag tgaatctcac 300

caacaagttg tggcagtggg tcaaccttta gcagtccagc ctcaagggac agtaatgctg 360

acttccaaaa atatccagtg tatgaggact ttacttaact tggcgcattg ccatggggct 420

gttcttggaa catcatggca acttgtcttg gcaactcttc agcatcttgt gtggattctg 480

ggattaaagc ctagtagtgg cggtgccttg aaacctggga gagctgtaga aggacccagt 540

acagttctaa caacagcagt gatgacagat ttaccagtga tttccaatat actttcaaga 600

ttgtttgaaa gctcacagta tcttgatgat gtatcactgc atcatttaat aaatgcactt 660

tgctccttgt ctctagaagc aatggatatg gcctatggaa ataataagga accatctctt 720

tttgctgttg ccaaattgtt agaaactggt ttagttaata tgcaccgaat agaaattctg 780

tggagacctc tgactggcca tctacttgag aaggtctgcc agcatccaaa ctctcgaatg 840

ggagaatggg gagcagaagc tttaacttct cttattaaag caggattaac atttaaccat 900

gatcctccac tctcacaaaa ccagaggctg cagttgcttt tattgaaccc gttaaaggag 960

atgtccaata ttaatcatcc agatattcga ctcaagcagt tagaatgcgt gttgcagatt 1020

ctgcagagtc agggagacaa tcttgggcct ggatggccat tagtgcttgg agtcatggga 1080

gcaatcagaa atgatcaagg agaatccttg atacgaactg cattccagtg tcttcagttg 1140

gttgtgacag attttctacc aacaatgcct tgtacttgcc tgcaaatagt tgtagatgtt 1200

gcaggtagct ttggcctcca taaccaagaa ctcaatatta gtttaacttc aataggttta 1260

ttgtggaata tttcagatta ttttttccaa agaggggaaa ctattgaaaa agaactaaat 1320

aaggaagagg cagcacagca aaagcaggca gaagagaaag gagttgtttt aaatcggcca 1380

ttccaccctg caccgccatt tgattgcttg tggttatgtc tttatgcaaa attgggtgaa 1440

ctatgtgtgg atccccgtcc tgctgtcagg aagagtgcag ggcaaactct gttttctaca 1500

attggtgcgc atggaacttt attacagcat tcaacctggc gcactgttat ctggaaggta 1560

ttg 1563

<210> SEQ ID NO 30

<211> LENGTH: 1768

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<220> FEATURE:

<221> NAME/KEY: sig_peptide

<222> LOCATION: (8)..(70)

<221> NAME/KEY: mat_peptide

<222> LOCATION: (71)..(1570)

<221> NAME/KEY: CDS

<222> LOCATION: (8)..(1570)

<400> SEQUENCE: 30

ggaagaa atg gtg aat gcc tgc tgg tgt ggt ctt ctt gct gca ctc tca 49

Met Val Asn Ala Cys Trp Cys Gly Leu Leu Ala Ala Leu Ser

-20 -15 -10

ctc ctt ctt gat gcc agc aca gat gaa gtt gcc act gag aat att tta 97

Leu Leu Leu Asp Ala Ser Thr Asp Glu Val Ala Thr Glu Asn Ile Leu

-5 -1 1 5

aaa gct gaa ctg act atg gct gct ctt tgt gga aga ctg ggc ctt gta 145

Lys Ala Glu Leu Thr Met Ala Ala Leu Cys Gly Arg Leu Gly Leu Val

10 15 20 25

act tca aga gat gcc ttt ata act gca ata tgc aaa ggt tcc ctg cct 193

Thr Ser Arg Asp Ala Phe Ile Thr Ala Ile Cys Lys Gly Ser Leu Pro

30 35 40

ccc cat tat gct ctt act gta ttg aat acc acc act gca gct aca ctt 241

Pro His Tyr Ala Leu Thr Val Leu Asn Thr Thr Thr Ala Ala Thr Leu

45 50 55

tcc aac aaa tca tat tcc gtt cag ggc caa agt gtt atg atg ata agt 289

Ser Asn Lys Ser Tyr Ser Val Gln Gly Gln Ser Val Met Met Ile Ser

60 65 70

cca tca agt gaa tct cac caa caa gtt gtg gca gtg ggt caa cct tta 337

Pro Ser Ser Glu Ser His Gln Gln Val Val Ala Val Gly Gln Pro Leu

75 80 85

gca gtc cag cct caa ggg aca gta atg ctg act tcc aaa aat atc cag 385

Ala Val Gln Pro Gln Gly Thr Val Met Leu Thr Ser Lys Asn Ile Gln

90 95 100 105

tgt atg agg act tta ctt aac ttg gcg cat tgc cat ggg gct gtt ctt 433

Cys Met Arg Thr Leu Leu Asn Leu Ala His Cys His Gly Ala Val Leu

110 115 120

gga aca tca tgg caa ctt gtc ttg gca act ctt cag cat ctt gtg tgg 481

Gly Thr Ser Trp Gln Leu Val Leu Ala Thr Leu Gln His Leu Val Trp

125 130 135

att ctg gga tta aag cct agt agt ggc ggt gcc ttg aaa cct ggg aga 529

Ile Leu Gly Leu Lys Pro Ser Ser Gly Gly Ala Leu Lys Pro Gly Arg

140 145 150

gct gta gaa gga ccc agt aca gtt cta aca aca gca gtg atg aca gat 577

Ala Val Glu Gly Pro Ser Thr Val Leu Thr Thr Ala Val Met Thr Asp

155 160 165

tta cca gtg att tcc aat ata ctt tca aga ttg ttt gaa agc tca cag 625

Leu Pro Val Ile Ser Asn Ile Leu Ser Arg Leu Phe Glu Ser Ser Gln

170 175 180 185

tat ctt gat gat gta tca ctg cat cat tta ata aat gca ctt tgc tcc 673

Tyr Leu Asp Asp Val Ser Leu His His Leu Ile Asn Ala Leu Cys Ser

190 195 200

ttg tct cta gaa gca atg gat atg gcc tat gga aat aat aag gaa cca 721

Leu Ser Leu Glu Ala Met Asp Met Ala Tyr Gly Asn Asn Lys Glu Pro

205 210 215

tct ctt ttt gct gtt gcc aaa ttg tta gaa act ggt tta gtt aat atg 769

Ser Leu Phe Ala Val Ala Lys Leu Leu Glu Thr Gly Leu Val Asn Met

220 225 230

cac cga ata gaa att ctg tgg aga cct ctg act ggc cat cta ctt gag 817

His Arg Ile Glu Ile Leu Trp Arg Pro Leu Thr Gly His Leu Leu Glu

235 240 245

aag gtc tgc cag cat cca aac tct cga atg gga gaa tgg gga gca gaa 865

Lys Val Cys Gln His Pro Asn Ser Arg Met Gly Glu Trp Gly Ala Glu

250 255 260 265

gct tta act tct ctt att aaa gca gga tta aca ttt aac cat gat cct 913

Ala Leu Thr Ser Leu Ile Lys Ala Gly Leu Thr Phe Asn His Asp Pro

270 275 280

cca ctc tca caa aac cag agg ctg cag ttg ctt tta ttg aac ccg tta 961

Pro Leu Ser Gln Asn Gln Arg Leu Gln Leu Leu Leu Leu Asn Pro Leu

285 290 295

aag gag atg tcc aat att aat cat cca gat att cga ctc aag cag tta 1009

Lys Glu Met Ser Asn Ile Asn His Pro Asp Ile Arg Leu Lys Gln Leu

300 305 310

gaa tgc gtg ttg cag att ctg cag agt cag gga gac aat ctt ggg cct 1057

Glu Cys Val Leu Gln Ile Leu Gln Ser Gln Gly Asp Asn Leu Gly Pro

315 320 325

gga tgg cca tta gtg ctt gga gtc atg gga gca atc aga aat gat caa 1105

Gly Trp Pro Leu Val Leu Gly Val Met Gly Ala Ile Arg Asn Asp Gln

330 335 340 345

gga gaa tcc ttg ata cga act gca ttc cag tgt ctt cag ttg gtt gtg 1153

Gly Glu Ser Leu Ile Arg Thr Ala Phe Gln Cys Leu Gln Leu Val Val

350 355 360

aca gat ttt cta cca aca atg cct tgt act tgc ctg caa ata gtt gta 1201

Thr Asp Phe Leu Pro Thr Met Pro Cys Thr Cys Leu Gln Ile Val Val

365 370 375

gat gtt gca ggt agc ttt ggc ctc cat aac caa gaa ctc aat att agt 1249

Asp Val Ala Gly Ser Phe Gly Leu His Asn Gln Glu Leu Asn Ile Ser

380 385 390

tta act tca ata ggt tta ttg tgg aat att tca gat tat ttt ttc caa 1297

Leu Thr Ser Ile Gly Leu Leu Trp Asn Ile Ser Asp Tyr Phe Phe Gln

395 400 405

aga ggg gaa act att gaa aaa gaa cta aat aag gaa gag gca gca cag 1345

Arg Gly Glu Thr Ile Glu Lys Glu Leu Asn Lys Glu Glu Ala Ala Gln

410 415 420 425

caa aag cag gca gaa gag aaa gga gtt gtt tta aat cgg cca ttc cac 1393

Gln Lys Gln Ala Glu Glu Lys Gly Val Val Leu Asn Arg Pro Phe His

430 435 440

cct gca ccg cca ttt gat tgc ttg tgg tta tgt ctt tat gca aaa ttg 1441

Pro Ala Pro Pro Phe Asp Cys Leu Trp Leu Cys Leu Tyr Ala Lys Leu

445 450 455

ggt gaa cta tgt gtg gat ccc cgt cct gct gtc agg aag agt gca ggg 1489

Gly Glu Leu Cys Val Asp Pro Arg Pro Ala Val Arg Lys Ser Ala Gly

460 465 470

caa act ctg ttt tct aca att ggt gcg cat gga act tta tta cag cat 1537

Gln Thr Leu Phe Ser Thr Ile Gly Ala His Gly Thr Leu Leu Gln His

475 480 485

tca acc tgg cgc act gtt atc tgg aag gta ttg taaaatagat tggactatca 1590

Ser Thr Trp Arg Thr Val Ile Trp Lys Val Leu

490 495 500

gcttttaatg agtcatgctt atatattaat actttttcag ttaaacttat ttcttttaat 1650

ttttaaagaa tttccatgca tttgtgtatt tgacaaaaca ggaaataact gtgtcatatt 1710

gtaaattgta cctcataaag agcaaattaa atattaacag ccttaaaaaa aaaaaaaa 1768

<210> SEQ ID NO 31

<211> LENGTH: 459

<212> TYPE: PRT

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 31

Met Val Asn Ala Cys Trp Cys Gly Leu Leu Ala Ala Leu Ser Leu Leu

-20 -15 -10

Leu Asp Ala Ser Thr Asp Glu Val Ala Thr Glu Asn Ile Leu Lys Ala

-5 -1 1 5 10

Glu Leu Thr Met Ala Ala Leu Cys Gly Arg Leu Gly Leu Val Thr Ser

15 20 25

Arg Asp Ala Phe Ile Thr Ala Ile Cys Lys Gly Ser Leu Pro Pro His

30 35 40

Tyr Ala Leu Thr Val Leu Asn Thr Thr Thr Ala Ala Thr Leu Ser Asn

45 50 55

Lys Ser Tyr Ser Val Gln Gly Gln Ser Val Met Met Ile Ser Pro Ser

60 65 70 75

Ser Glu Ser His Gln Gln Val Val Ala Val Gly Gln Pro Leu Ala Val

80 85 90

Gln Pro Gln Gly Thr Val Met Leu Thr Ser Lys Asn Ile Gln Cys Met

95 100 105

Arg Thr Leu Leu Asn Leu Ala His Cys His Gly Ala Val Leu Gly Thr

110 115 120

Ser Trp Gln Leu Val Leu Ala Thr Leu Gln His Leu Val Trp Ile Leu

125 130 135

Gly Leu Lys Pro Ser Ser Gly Gly Ala Leu Lys Pro Gly Arg Ala Val

140 145 150 155

Glu Gly Pro Ser Thr Val Leu Thr Thr Ala Val Met Thr Asp Leu Pro

160 165 170

Val Ile Ser Asn Ile Leu Ser Arg Leu Phe Glu Ser Ser Arg Tyr Leu

175 180 185

Asp Asp Val Ser Leu His His Leu Ile Asn Ala Leu Cys Ser Leu Ser

190 195 200

Leu Glu Ala Met Asp Met Ala Tyr Gly Asn Asn Lys Glu Pro Ser Leu

205 210 215

Phe Ala Val Ala Lys Leu Leu Glu Thr Gly Leu Val Asn Met His Arg

220 225 230 235

Ile Glu Ile Leu Trp Arg Pro Leu Thr Gly His Leu Leu Glu Val Cys

240 245 250

Gln His Pro Asn Ser Arg Met Arg Glu Trp Gly Ala Glu Ala Leu Thr

255 260 265

Ser Leu Ile Lys Ala Gly Leu Thr Phe Asn His Asp Pro Pro Leu Ser

270 275 280

Gln Asn Gln Arg Leu Gln Leu Leu Leu Leu Asn Pro Leu Lys Glu Met

285 290 295

Ser Asn Ile Asn His Pro Asp Ile Arg Leu Lys Gln Leu Glu Cys Val

300 305 310 315

Leu Gln Ile Leu Gln Ser Gln Gly Asp Ser Leu Gly Pro Gly Trp Pro

320 325 330

Leu Val Leu Gly Val Met Gly Ala Ile Arg Asn Asp Gln Gly Glu Ser

335 340 345

Leu Ile Arg Thr Ala Phe Gln Cys Leu Gln Leu Val Val Thr Glu Ile

350 355 360

Ile Phe Val Leu Lys Ala Val Ser Thr Leu Ile Asp Ser Leu Lys Lys

365 370 375

Thr Gln Pro Glu Asn Val Asp Gly Asn Thr Trp Ala Gln Val Ile Ala

380 385 390 395

Leu Tyr Pro Thr Leu Val Glu Cys Ile Ala Cys Pro Ser Ser Glu Val

400 405 410

Cys Ser Ala Leu Lys Glu Ala Leu Val Pro Phe Lys Asp Phe Met Gln

415 420 425

Pro Pro Ala Ser Arg Val Gln Asn Gly Glu Ser

430 435

<210> SEQ ID NO 32

<211> LENGTH: 1377

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 32

atggtgaatg cctgctggtg tggtcttctt gctgcactct cactccttct tgatgccagc 60

acagatgaag ttgccactga gaatatttta aaagctgaac tgactatggc tgctctttgt 120

ggaagactgg gccttgtaac ttcaagagat gcctttataa ctgcaatatg caaaggttcc 180

ctgcctcccc attatgctct tactgtattg aataccacca ctgcagctac actttccaac 240

aaatcatatt ccgttcaggg ccaaagtgtt atgatgataa gtccatcaag tgaatctcac 300

caacaagttg tggcagtggg tcaaccttta gcagtccagc ctcaagggac agtaatgctg 360

acttccaaaa atatccagtg tatgaggact ttacttaact tggcgcattg ccatggggct 420

gttcttggaa catcatggca acttgtcttg gcaactcttc agcatcttgt gtggattctg 480

ggattaaagc ctagtagtgg cggtgccttg aaacctggga gagctgtaga aggacccagt 540

acagttctaa caacagcagt gatgacagat ttaccagtga tttccaatat actttcaaga 600

ttgtttgaaa gctcacggta tcttgatgat gtatcactgc atcatttaat aaatgcactt 660

tgctccttgt ctctagaagc aatggatatg gcctatggaa ataataagga accatctctt 720

tttgctgttg ccaaattgtt agaaactggt ttagttaata tgcaccgaat agaaattctg 780

tggagacctc tgactggcca tctacttgag gtctgccagc atccaaactc tcgaatgaga 840

gaatggggag cagaagcttt aacttctctt attaaagcag gattaacatt taaccatgat 900

cctccactct cacaaaacca gaggctgcag ttgcttttat tgaacccgtt aaaggagatg 960

tccaatatta atcatccaga tattcgactc aagcagttag aatgcgtgtt gcagattctg 1020

cagagtcagg gagacagtct tgggcctgga tggccattag tgcttggagt catgggagca 1080

atcagaaatg atcaaggaga atccttgata cgaactgcat tccagtgtct tcagttggtt 1140

gtaacagaaa ttatatttgt tttaaaagca gtcagtactc ttattgattc acttaagaaa 1200

actcagcctg agaatgttga tggaaatacc tgggcacaag taattgcctt atacccaact 1260

ttagtagaat gcatcgcctg tccttcttca gaagtctgtt ctgcacttaa agaggcacta 1320

gttcctttta aggatttcat gcagccacca gcatccagag ttcaaaatgg agaatct 1377

<210> SEQ ID NO 33

<211> LENGTH: 2009

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<220> FEATURE:

<221> NAME/KEY: sig_peptide

<222> LOCATION: (8)..(70)

<221> NAME/KEY: mat_peptide

<222> LOCATION: (71)..(1384)

<221> NAME/KEY: CDS

<222> LOCATION: (8)..(1384)

<400> SEQUENCE: 33

ggaagaa atg gtg aat gcc tgc tgg tgt ggt ctt ctt gct gca ctc tca 49

Met Val Asn Ala Cys Trp Cys Gly Leu Leu Ala Ala Leu Ser

-20 -15 -10

ctc ctt ctt gat gcc agc aca gat gaa gtt gcc act gag aat att tta 97

Leu Leu Leu Asp Ala Ser Thr Asp Glu Val Ala Thr Glu Asn Ile Leu

-5 -1 1 5

aaa gct gaa ctg act atg gct gct ctt tgt gga aga ctg ggc ctt gta 145

Lys Ala Glu Leu Thr Met Ala Ala Leu Cys Gly Arg Leu Gly Leu Val

10 15 20 25

act tca aga gat gcc ttt ata act gca ata tgc aaa ggt tcc ctg cct 193

Thr Ser Arg Asp Ala Phe Ile Thr Ala Ile Cys Lys Gly Ser Leu Pro

30 35 40

ccc cat tat gct ctt act gta ttg aat acc acc act gca gct aca ctt 241

Pro His Tyr Ala Leu Thr Val Leu Asn Thr Thr Thr Ala Ala Thr Leu

45 50 55

tcc aac aaa tca tat tcc gtt cag ggc caa agt gtt atg atg ata agt 289

Ser Asn Lys Ser Tyr Ser Val Gln Gly Gln Ser Val Met Met Ile Ser

60 65 70

cca tca agt gaa tct cac caa caa gtt gtg gca gtg ggt caa cct tta 337

Pro Ser Ser Glu Ser His Gln Gln Val Val Ala Val Gly Gln Pro Leu

75 80 85

gca gtc cag cct caa ggg aca gta atg ctg act tcc aaa aat atc cag 385

Ala Val Gln Pro Gln Gly Thr Val Met Leu Thr Ser Lys Asn Ile Gln

90 95 100 105

tgt atg agg act tta ctt aac ttg gcg cat tgc cat ggg gct gtt ctt 433

Cys Met Arg Thr Leu Leu Asn Leu Ala His Cys His Gly Ala Val Leu

110 115 120

gga aca tca tgg caa ctt gtc ttg gca act ctt cag cat ctt gtg tgg 481

Gly Thr Ser Trp Gln Leu Val Leu Ala Thr Leu Gln His Leu Val Trp

125 130 135

att ctg gga tta aag cct agt agt ggc ggt gcc ttg aaa cct ggg aga 529

Ile Leu Gly Leu Lys Pro Ser Ser Gly Gly Ala Leu Lys Pro Gly Arg

140 145 150

gct gta gaa gga ccc agt aca gtt cta aca aca gca gtg atg aca gat 577

Ala Val Glu Gly Pro Ser Thr Val Leu Thr Thr Ala Val Met Thr Asp

155 160 165

tta cca gtg att tcc aat ata ctt tca aga ttg ttt gaa agc tca cgg 625

Leu Pro Val Ile Ser Asn Ile Leu Ser Arg Leu Phe Glu Ser Ser Arg

170 175 180 185

tat ctt gat gat gta tca ctg cat cat tta ata aat gca ctt tgc tcc 673

Tyr Leu Asp Asp Val Ser Leu His His Leu Ile Asn Ala Leu Cys Ser

190 195 200

ttg tct cta gaa gca atg gat atg gcc tat gga aat aat aag gaa cca 721

Leu Ser Leu Glu Ala Met Asp Met Ala Tyr Gly Asn Asn Lys Glu Pro

205 210 215

tct ctt ttt gct gtt gcc aaa ttg tta gaa act ggt tta gtt aat atg 769

Ser Leu Phe Ala Val Ala Lys Leu Leu Glu Thr Gly Leu Val Asn Met

220 225 230

cac cga ata gaa att ctg tgg aga cct ctg act ggc cat cta ctt gag 817

His Arg Ile Glu Ile Leu Trp Arg Pro Leu Thr Gly His Leu Leu Glu

235 240 245

gtc tgc cag cat cca aac tct cga atg aga gaa tgg gga gca gaa gct 865

Val Cys Gln His Pro Asn Ser Arg Met Arg Glu Trp Gly Ala Glu Ala

250 255 260 265

tta act tct ctt att aaa gca gga tta aca ttt aac cat gat cct cca 913

Leu Thr Ser Leu Ile Lys Ala Gly Leu Thr Phe Asn His Asp Pro Pro

270 275 280

ctc tca caa aac cag agg ctg cag ttg ctt tta ttg aac ccg tta aag 961

Leu Ser Gln Asn Gln Arg Leu Gln Leu Leu Leu Leu Asn Pro Leu Lys

285 290 295

gag atg tcc aat att aat cat cca gat att cga ctc aag cag tta gaa 1009

Glu Met Ser Asn Ile Asn His Pro Asp Ile Arg Leu Lys Gln Leu Glu

300 305 310

tgc gtg ttg cag att ctg cag agt cag gga gac agt ctt ggg cct gga 1057

Cys Val Leu Gln Ile Leu Gln Ser Gln Gly Asp Ser Leu Gly Pro Gly

315 320 325

tgg cca tta gtg ctt gga gtc atg gga gca atc aga aat gat caa gga 1105

Trp Pro Leu Val Leu Gly Val Met Gly Ala Ile Arg Asn Asp Gln Gly

330 335 340 345

gaa tcc ttg ata cga act gca ttc cag tgt ctt cag ttg gtt gta aca 1153

Glu Ser Leu Ile Arg Thr Ala Phe Gln Cys Leu Gln Leu Val Val Thr

350 355 360

gaa att ata ttt gtt tta aaa gca gtc agt act ctt att gat tca ctt 1201

Glu Ile Ile Phe Val Leu Lys Ala Val Ser Thr Leu Ile Asp Ser Leu

365 370 375

aag aaa act cag cct gag aat gtt gat gga aat acc tgg gca caa gta 1249

Lys Lys Thr Gln Pro Glu Asn Val Asp Gly Asn Thr Trp Ala Gln Val

380 385 390

att gcc tta tac cca act tta gta gaa tgc atc gcc tgt cct tct tca 1297

Ile Ala Leu Tyr Pro Thr Leu Val Glu Cys Ile Ala Cys Pro Ser Ser

395 400 405

gaa gtc tgt tct gca ctt aaa gag gca cta gtt cct ttt aag gat ttc 1345

Glu Val Cys Ser Ala Leu Lys Glu Ala Leu Val Pro Phe Lys Asp Phe

410 415 420 425

atg cag cca cca gca tcc aga gtt caa aat gga gaa tct tgaccggcta 1394

Met Gln Pro Pro Ala Ser Arg Val Gln Asn Gly Glu Ser

430 435

caatatattt gaaagcagga agatagtcta aaaaatgttt gctcctaatt gagtcttctg 1454

tgagaaggac atttcttact gcagataatt cttggcagct gttgttggcc tcctttaaat 1514

tctacttacc tgagttcagt aattcatatt acaggcttgc acatcaacaa aggctcctga 1574

atgaacagca gtgcaaggct ttaataaatt aaactgatgg gagggataat taacactaca 1634

gtatacatgc taccatatct ccagttggtg atttaaagtg agcttatgta cagtttgtgg 1694

tgtatgtgtt aatgatgtac tttttaaaaa gaaagaagag atatttcaat tcagtcagat 1754

ttattagtct ggtgtttttg cacccttttt caagtacaaa atcgtactag aattttatgc 1814

aagatggtac tgtaacattc catattatct ataaccagcc tctgttaaca aagggaactg 1874

atatacttgt gtgtataata aatggtacag ttctgtataa aatagtgcat ttatttaaat 1934

tttaaaagta ttgataatgt taaatgctta aagctctatt tattactaaa aaaaaaaaaa 1994

aaaaaaaaaa aaaaa 2009

<210> SEQ ID NO 34

<211> LENGTH: 185

<212> TYPE: PRT

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 34

Met Phe Ser His Leu Pro Phe Asp Cys Val Leu Leu Leu Leu Leu Leu

-20 -15 -10

Leu Leu Thr Arg Ser Ser Glu Val Glu Tyr Arg Ala Glu Val Gly Gln

-5 -1 1 5 10

Asn Ala Tyr Leu Pro Cys Phe Tyr Thr Pro Ala Ala Pro Gly Asn Leu

15 20 25

Val Pro Val Cys Trp Gly Lys Gly Ala Cys Pro Val Phe Glu Cys Gly

30 35 40

Asn Val Val Leu Arg Thr Asp Glu Arg Asp Val Asn Tyr Trp Thr Ser

45 50 55

Arg Tyr Trp Leu Asn Gly Asp Phe Arg Lys Gly Asp Val Ser Leu Thr

60 65 70 75

Ile Glu Asn Val Thr Leu Ala Asp Ser Gly Ile Tyr Cys Cys Arg Ile

80 85 90

Gln Ile Pro Gly Ile Met Asn Asp Glu Lys Phe Asn Leu Lys Leu Val

95 100 105

Ile Lys Pro Ala Lys Val Thr Pro Ala Pro Thr Leu Gln Arg Asp Phe

110 115 120

Thr Ala Ala Phe Pro Arg Met Leu Thr Thr Arg Gly His Gly Pro Ala

125 130 135

Glu Thr Gln Thr Leu Gly Ser Leu Pro Asp Ile Asn Leu Thr Gly Ile

140 145 150 155

Leu Ile Ala Lys Arg Arg Tyr Arg Ile

160

<210> SEQ ID NO 35

<211> LENGTH: 555

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 35

atgttttcac atcttccctt tgactgtgtc ctgctgctgc tgctgctact acttacaagg 60

tcctcagaag tggaatacag agcggaggtc ggtcagaatg cctatctgcc ctgcttctac 120

accccagccg ccccagggaa cctcgtgccc gtctgctggg gcaaaggagc ctgtcctgtg 180

tttgaatgtg gcaacgtggt gctcaggact gatgaaaggg atgtgaatta ttggacatcc 240

agatactggc taaatgggga tttccgcaaa ggagatgtgt ccctgaccat agagaatgtg 300

actctagcag acagtgggat ctactgctgc cggatccaaa tcccaggcat aatgaatgat 360

gaaaaattta acctgaagtt ggtcatcaaa ccagccaagg tcacccctgc accgactctg 420

cagagagact tcactgcagc ctttccaagg atgcttacca ccaggggaca tggcccagca 480

gagacacaga cactggggag cctccctgat ataaatctaa caggtattct catagcaaag 540

agaagataca gaatt 555

<210> SEQ ID NO 36

<211> LENGTH: 2091

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<220> FEATURE:

<221> NAME/KEY: sig_peptide

<222> LOCATION: (53)..(115)

<221> NAME/KEY: mat_peptide

<222> LOCATION: (116)..(607)

<221> NAME/KEY: CDS

<222> LOCATION: (53)..(607)

<400> SEQUENCE: 36

gttaaaactg tgcctaacag aggtgtcctc tgacttttct tctgcaagct cc atg ttt 58

Met Phe

-20

tca cat ctt ccc ttt gac tgt gtc ctg ctg ctg ctg ctg cta cta ctt 106

Ser His Leu Pro Phe Asp Cys Val Leu Leu Leu Leu Leu Leu Leu Leu

-15 -10 -5

aca agg tcc tca gaa gtg gaa tac aga gcg gag gtc ggt cag aat gcc 154

Thr Arg Ser Ser Glu Val Glu Tyr Arg Ala Glu Val Gly Gln Asn Ala

-1 1 5 10

tat ctg ccc tgc ttc tac acc cca gcc gcc cca ggg aac ctc gtg ccc 202

Tyr Leu Pro Cys Phe Tyr Thr Pro Ala Ala Pro Gly Asn Leu Val Pro

15 20 25

gtc tgc tgg ggc aaa gga gcc tgt cct gtg ttt gaa tgt ggc aac gtg 250

Val Cys Trp Gly Lys Gly Ala Cys Pro Val Phe Glu Cys Gly Asn Val

30 35 40 45

gtg ctc agg act gat gaa agg gat gtg aat tat tgg aca tcc aga tac 298

Val Leu Arg Thr Asp Glu Arg Asp Val Asn Tyr Trp Thr Ser Arg Tyr

50 55 60

tgg cta aat ggg gat ttc cgc aaa gga gat gtg tcc ctg acc ata gag 346

Trp Leu Asn Gly Asp Phe Arg Lys Gly Asp Val Ser Leu Thr Ile Glu

65 70 75

aat gtg act cta gca gac agt ggg atc tac tgc tgc cgg atc caa atc 394

Asn Val Thr Leu Ala Asp Ser Gly Ile Tyr Cys Cys Arg Ile Gln Ile

80 85 90

cca ggc ata atg aat gat gaa aaa ttt aac ctg aag ttg gtc atc aaa 442

Pro Gly Ile Met Asn Asp Glu Lys Phe Asn Leu Lys Leu Val Ile Lys

95 100 105

cca gcc aag gtc acc cct gca ccg act ctg cag aga gac ttc act gca 490

Pro Ala Lys Val Thr Pro Ala Pro Thr Leu Gln Arg Asp Phe Thr Ala

110 115 120 125

gcc ttt cca agg atg ctt acc acc agg gga cat ggc cca gca gag aca 538

Ala Phe Pro Arg Met Leu Thr Thr Arg Gly His Gly Pro Ala Glu Thr

130 135 140

cag aca ctg ggg agc ctc cct gat ata aat cta aca ggt att ctc ata 586

Gln Thr Leu Gly Ser Leu Pro Asp Ile Asn Leu Thr Gly Ile Leu Ile

145 150 155

gca aag aga aga tac aga att taagcctcat ctctttggcc aacctccctc 637

Ala Lys Arg Arg Tyr Arg Ile

160

cctcaggatt ggcaaatgca gtagcagagg gaattcgctc agaagaaaac atctatacca 697

ttgaagagaa cgtatatgaa gtggaggagc ccaatgagta ttattgctat gtcagcagca 757

ggcagcaacc ctcacaacct ttgggttgtc gctttgcaat gccatagatc caaccacctt 817

atttttgagc ttggtgtttt gtctttttca gaaactatga gctgtgtcac ctgactggtt 877

ttggaggttc tgtccactgc tatggagcag agttttccca ttttcagaag ataatgactc 937

acatgggaat tgaactggga cctgcactga acttaaacag gcatgtcatt gcctctgtat 997

ttaagccaac agagttaccc aacccagaga ctgttaatca tggatgttag agctcaaacg 1057

ggcttttata tacactagga attcttgacg tggggtctct ggagctccag gaaattcggg 1117

cacatcatat gtccatgaaa cttcagataa actagggaaa actgggtgct gaggtgaaag 1177

cataactttt ttggcacaga aagtctaaag gggccactga ttttcaaaga gatctgtgat 1237

ccctttttgt tttttgtttt tgagatggag tcttgctctg ttgcccaggc tggagtgcaa 1297

tggcacaatc tcggctcact gcaagccccg cctcctgggt tcaagcgatt ctcctgcctc 1357

agcctcctga gtggctggga ttacaggcat gcaccaccat gcccagctaa tttgttgtat 1417

ttttagtaga gacagggttt caccatgttg gccagtgtgg tctcaaactc ctgacctcat 1477

gatttgcctg cctcggcccc ccaaagcact gggattacag gcgtgagcca ccacatccag 1537

ccagtgatcc ttaaaagatt aagagatgac tggactaggt ctaccttgat cttgaagatt 1597

cccttggaat gttgagattt aggcttattt gagcactacc tgcccaactg tcagtgccag 1657

tgcatagccc ttcttttgtc tcccttatga agactgccct gcagggctga gatgtggcag 1717

gagctcccag ggaaaaagga agtgcatttg attggtgtgt attggccaag ttttgcttgt 1777

tgtgtgcttg aaagaaaata tctctgacca acttctgtat tcgtggacca aactgaagct 1837

atatttttca cagaagaaga agcagtgacg gggacacaaa ttctgttgcc tggtggaaag 1897

aaggcaaagg ccttcagcaa tctatattac cagcgctgga tcctttgaca gagagtggtc 1957

cctaaactta aatttcaaga cggtataggc ttgatctgtc ttgcttattg ttgccccctg 2017

cgcctagcac aattctgaca cacaattgga acttactaaa aatttttttt actgaaaaaa 2077

aaaaaaaaaa aaaa 2091

<210> SEQ ID NO 37

<211> LENGTH: 98

<212> TYPE: PRT

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 37

Met Val Arg Ile Leu Arg Thr Val Pro Phe Leu Pro Leu Leu Gly Gly

-15 -10 -5 -1

Cys Ile Asp Asp Thr Ile Leu Ser Arg Gln Gly Phe Ile Asn Tyr Ser

1 5 10 15

Lys Leu Pro Ser Leu Pro Leu Val Gln Gly Glu Leu Val Gly Gly Leu

20 25 30

Thr Cys Leu Thr Ala Gln Thr His Ser Leu Leu Gln His Gln Pro Leu

35 40 45

Gln Leu Thr Thr Leu Leu Asp Gln Tyr Ile Arg Glu Gln Arg Glu Lys

50 55 60

Asp Ser Val Met Ser Ala Asn Gly Lys Pro Asp Pro Asp Thr Val Pro

65 70 75 80

Asp Ser

<210> SEQ ID NO 38

<211> LENGTH: 294

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 38

atggtacgga tcttaaggac tgtgccattc ctgccgctgc taggtggctg cattgatgac 60

accatcctca gcaggcaggg ctttatcaac tactccaagc tccccagcct gcccctggtg 120

cagggggagc ttgtaggagg cctcacctgc ctcacagccc agacccactc cctgctccag 180

caccagcccc tccagctgac caccctgttg gaccagtaca tcagagagca acgcgagaag 240

gattctgtca tgtcggccaa tgggaagcca gatcctgaca ctgttccgga ctcg 294

<210> SEQ ID NO 39

<211> LENGTH: 1094

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<220> FEATURE:

<221> NAME/KEY: sig_peptide

<222> LOCATION: (22)..(69)

<221> NAME/KEY: mat_peptide

<222> LOCATION: (70)..(315)

<221> NAME/KEY: CDS

<222> LOCATION: (22)..(315)

<400> SEQUENCE: 39

gaagagccca aggtcaagga g atg gta cgg atc tta agg act gtg cca ttc 51

Met Val Arg Ile Leu Arg Thr Val Pro Phe

-15 -10

ctg ccg ctg cta ggt ggc tgc att gat gac acc atc ctc agc agg cag 99

Leu Pro Leu Leu Gly Gly Cys Ile Asp Asp Thr Ile Leu Ser Arg Gln

-5 -1 1 5 10

ggc ttt atc aac tac tcc aag ctc ccc agc ctg ccc ctg gtg cag ggg 147

Gly Phe Ile Asn Tyr Ser Lys Leu Pro Ser Leu Pro Leu Val Gln Gly

15 20 25

gag ctt gta gga ggc ctc acc tgc ctc aca gcc cag acc cac tcc ctg 195

Glu Leu Val Gly Gly Leu Thr Cys Leu Thr Ala Gln Thr His Ser Leu

30 35 40

ctc cag cac cag ccc ctc cag ctg acc acc ctg ttg gac cag tac atc 243

Leu Gln His Gln Pro Leu Gln Leu Thr Thr Leu Leu Asp Gln Tyr Ile

45 50 55

aga gag caa cgc gag aag gat tct gtc atg tcg gcc aat ggg aag cca 291

Arg Glu Gln Arg Glu Lys Asp Ser Val Met Ser Ala Asn Gly Lys Pro

60 65 70

gat cct gac act gtt ccg gac tcg tagccagcct gtttagccag ccctgcgcat 345

Asp Pro Asp Thr Val Pro Asp Ser

75 80

aaatacactc tgcgttattg gctgtgctct cctcaatggg acatgtggaa gaacttgggg 405

tcgaggagtg tgtttgtcac ttggttttca ctagtaatga tattgtcagg tatagggcca 465

cttggagatg cagaggattc catttcagat gtcagtcacc ggcttcgtcc ttagttttcc 525

caacttggga cgtgatagga gcaaagtctc tccattctcc aggtccaagg cagagatcct 585

gaaaagatag ggctattgtc ccctgcctcc ttggtcactg cctcttgctg cacgggctcc 645

tgagcccacc cccttggggc acaacctgcc actgccacag tagctcaacc aagcagttgt 705

gctgagaatg gcacctggtg agagcctgct gtgtgccagg ctttgtgctg agtgctgtac 765

atgtattagt tcctttactg ctgaccacat tgtacccatt tcacagagaa ggagcagaga 825

aattaagtgg cttgctcaag gtcatgcagt tagtaagtgg cagaacaggg acttggaacc 885

aagccctctg ctctgaagac cgcgtcctga atttcttcac tagagcttcc tcatcaggtt 945

acccagaagt gggtcccatc caccatccag gtgtgcttgg atgttagttc tccaccctcg 1005

aggtgtacgc tgtgaaaagt ttgggagcac tgctttataa taaaatgaaa tatattataa 1065

aaaaaaaaaa aaaaaaaaaa aaaaaaaaa 1094

<210> SEQ ID NO 40

<211> LENGTH: 474

<212> TYPE: PRT

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 40

Met Tyr Thr Val Gly Ala Pro His Thr Trp Pro His Ile Val Ala Ala

-20 -15 -10

Leu Val Trp Leu Ile Asp Cys Ile Lys Ile His Thr Ala Met Lys Glu

-5 -1 1 5

Ser Ser Pro Leu Phe Asp Asp Gly Gln Pro Trp Gly Glu Glu Thr Glu

10 15 20 25

Asp Gly Ile Met His Asn Lys Leu Phe Leu Asp Tyr Thr Ile Lys Cys

30 35 40

Tyr Glu Ser Phe Met Ser Gly Ala Asp Ser Phe Asp Glu Met Asn Ala

45 50 55

Glu Leu Gln Ser Lys Leu Lys Asp Leu Phe Asn Val Asp Ala Phe Lys

60 65 70

Leu Glu Ser Leu Glu Ala Lys Asn Arg Ala Leu Asn Glu Gln Ile Ala

75 80 85

Arg Leu Glu Gln Glu Arg Glu Lys Glu Pro Asn Arg Leu Glu Ser Leu

90 95 100 105

Arg Lys Leu Lys Ala Ser Leu Gln Gly Asp Val Gln Lys Tyr Gln Ala

110 115 120

Tyr Met Ser Asn Leu Glu Ser His Ser Ala Ile Leu Asp Gln Lys Leu

125 130 135

Asn Gly Leu Asn Glu Glu Ile Ala Arg Val Glu Leu Glu Cys Glu Thr

140 145 150

Ile Lys Gln Glu Asn Thr Arg Leu Gln Asn Ile Ile Asp Asn Gln Lys

155 160 165

Tyr Ser Val Ala Asp Ile Glu Arg Ile Asn His Glu Arg Asn Glu Leu

170 175 180 185

Gln Gln Thr Ile Asn Lys Leu Thr Lys Asp Leu Glu Ala Glu Gln Gln

190 195 200

Lys Leu Trp Asn Glu Glu Leu Lys Tyr Ala Arg Gly Lys Glu Ala Ile

205 210 215

Glu Thr Gln Leu Ala Glu Tyr His Lys Leu Ala Arg Lys Leu Lys Leu

220 225 230

Ile Pro Lys Gly Ala Glu Asn Ser Lys Gly Tyr Asp Phe Glu Ile Lys

235 240 245

Phe Asn Pro Glu Ala Gly Ala Asn Cys Leu Val Lys Tyr Arg Ala Gln

250 255 260 265

Val Tyr Val Pro Leu Lys Glu Leu Leu Asn Glu Thr Glu Glu Glu Ile

270 275 280

Asn Lys Ala Leu Asn Lys Lys Met Gly Leu Glu Asp Thr Leu Glu Gln

285 290 295

Leu Asn Ala Met Ile Thr Glu Ser Lys Arg Ser Val Gly Thr Leu Lys

300 305 310

Glu Glu Val Gln Lys Leu Asp Asp Leu Tyr Gln Gln Lys Ile Lys Glu

315 320 325

Ala Glu Glu Glu Asp Glu Lys Cys Ala Ser Glu Leu Glu Ser Leu Glu

330 335 340 345

Lys His Lys His Leu Leu Glu Ser Thr Val Asn Gln Gly Leu Ser Glu

350 355 360

Ala Met Asn Glu Leu Asp Ala Val Gln Arg Glu Tyr Gln Leu Val Val

365 370 375

Gln Thr Thr Thr Glu Glu Arg Arg Lys Val Gly Asn Asn Leu Gln Arg

380 385 390

Leu Leu Glu Met Val Ala Thr His Val Gly Ser Val Glu Lys His Leu

395 400 405

Glu Glu Gln Ile Ala Lys Val Asp Arg Glu Tyr Glu Glu Cys Met Ser

410 415 420 425

Glu Asp Leu Ser Glu Asn Ile Lys Glu Ile Arg Asp Lys Tyr Glu Lys

430 435 440

Lys Ala Thr Leu Ile Lys Ser Ser Glu Glu

445 450

<210> SEQ ID NO 41

<211> LENGTH: 1422

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 41

atgtacacag tgggggctcc tcatacatgg cctcacattg tggcagcctt agtttggcta 60

atagactgca tcaagataca tactgccatg aaagaaagct cacctttatt tgatgatggg 120

cagccttggg gagaagaaac tgaagatgga attatgcata ataagttgtt tttggactac 180

accataaaat gctatgagag ttttatgagt ggtgccgaca gctttgatga gatgaatgca 240

gagctgcagt caaaactgaa ggatttattt aatgtggatg cttttaagct ggaatcatta 300

gaagcaaaaa acagagcatt gaatgaacag attgcaagat tggaacaaga aagagaaaaa 360

gaaccgaatc gtctagagtc gttgagaaaa ctgaaggctt ccttacaagg agatgttcaa 420

aagtatcagg catacatgag caatttggag tctcattcag ccattcttga ccagaaatta 480

aatggtctca atgaggaaat tgctagagta gaactagaat gtgaaacaat aaaacaggag 540

aacactcgac tacagaatat cattgacaac cagaagtact cagttgcaga cattgagcga 600

ataaatcatg aaagaaatga attgcagcag actattaata aattaaccaa ggacctggaa 660

gctgaacaac agaagttgtg gaatgaggag ttaaaatatg ccagaggcaa agaagcgatt 720

gaaacacaat tagcagagta tcacaaattg gctagaaaat taaaacttat tcctaaaggt 780

gctgagaatt ccaaaggtta tgactttgaa attaagttta atcccgaggc tggtgccaac 840

tgccttgtca aatacagggc tcaagtttat gtacctctta aggaactcct gaatgaaact 900

gaagaagaaa ttaataaagc cctaaataaa aaaatgggtt tggaggatac tttagaacaa 960

ttgaatgcaa tgataacaga aagcaagaga agtgtgggaa ctctgaaaga agaagttcaa 1020

aagctggatg atctttacca acaaaaaatt aaggaagcag aggaagagga tgaaaaatgt 1080

gccagtgagc ttgagtcctt ggagaaacac aagcacctgc tagaaagtac tgttaaccag 1140

gggctcagtg aagctatgaa tgaattagat gctgttcagc gggaatacca actagttgtg 1200

caaaccacga ctgaagaaag acgaaaagtg ggaaataact tgcaacgtct gttagagatg 1260

gttgctacac atgttgggtc tgtagagaaa catcttgagg agcagattgc taaagttgat 1320

agagaatatg aagaatgcat gtcagaagat ctctcggaaa atattaaaga gattagagat 1380

aagtatgaga agaaagctac tctaattaag tcttctgaag aa 1422

<210> SEQ ID NO 42

<211> LENGTH: 1613

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<220> FEATURE:

<221> NAME/KEY: sig_peptide

<222> LOCATION: (99)..(167)

<221> NAME/KEY: mat_peptide

<222> LOCATION: (168)..(1520)

<221> NAME/KEY: CDS

<222> LOCATION: (99)..(1520)

<400> SEQUENCE: 42

tgtgcccctc atacgaactt cctgacacaa agtttgaaga agaggttcca agaatcttta 60

aagaccttgg gtatcctttt gcactatcca aaagctcc atg tac aca gtg ggg gct 116

Met Tyr Thr Val Gly Ala

-20

cct cat aca tgg cct cac att gtg gca gcc tta gtt tgg cta ata gac 164

Pro His Thr Trp Pro His Ile Val Ala Ala Leu Val Trp Leu Ile Asp

-15 -10 -5

tgc atc aag ata cat act gcc atg aaa gaa agc tca cct tta ttt gat 212

Cys Ile Lys Ile His Thr Ala Met Lys Glu Ser Ser Pro Leu Phe Asp

-1 1 5 10 15

gat ggg cag cct tgg gga gaa gaa act gaa gat gga att atg cat aat 260

Asp Gly Gln Pro Trp Gly Glu Glu Thr Glu Asp Gly Ile Met His Asn

20 25 30

aag ttg ttt ttg gac tac acc ata aaa tgc tat gag agt ttt atg agt 308

Lys Leu Phe Leu Asp Tyr Thr Ile Lys Cys Tyr Glu Ser Phe Met Ser

35 40 45

ggt gcc gac agc ttt gat gag atg aat gca gag ctg cag tca aaa ctg 356

Gly Ala Asp Ser Phe Asp Glu Met Asn Ala Glu Leu Gln Ser Lys Leu

50 55 60

aag gat tta ttt aat gtg gat gct ttt aag ctg gaa tca tta gaa gca 404

Lys Asp Leu Phe Asn Val Asp Ala Phe Lys Leu Glu Ser Leu Glu Ala

65 70 75

aaa aac aga gca ttg aat gaa cag att gca aga ttg gaa caa gaa aga 452

Lys Asn Arg Ala Leu Asn Glu Gln Ile Ala Arg Leu Glu Gln Glu Arg

80 85 90 95

gaa aaa gaa ccg aat cgt cta gag tcg ttg aga aaa ctg aag gct tcc 500

Glu Lys Glu Pro Asn Arg Leu Glu Ser Leu Arg Lys Leu Lys Ala Ser

100 105 110

tta caa gga gat gtt caa aag tat cag gca tac atg agc aat ttg gag 548

Leu Gln Gly Asp Val Gln Lys Tyr Gln Ala Tyr Met Ser Asn Leu Glu

115 120 125

tct cat tca gcc att ctt gac cag aaa tta aat ggt ctc aat gag gaa 596

Ser His Ser Ala Ile Leu Asp Gln Lys Leu Asn Gly Leu Asn Glu Glu

130 135 140

att gct aga gta gaa cta gaa tgt gaa aca ata aaa cag gag aac act 644

Ile Ala Arg Val Glu Leu Glu Cys Glu Thr Ile Lys Gln Glu Asn Thr

145 150 155

cga cta cag aat atc att gac aac cag aag tac tca gtt gca gac att 692

Arg Leu Gln Asn Ile Ile Asp Asn Gln Lys Tyr Ser Val Ala Asp Ile

160 165 170 175

gag cga ata aat cat gaa aga aat gaa ttg cag cag act att aat aaa 740

Glu Arg Ile Asn His Glu Arg Asn Glu Leu Gln Gln Thr Ile Asn Lys

180 185 190

tta acc aag gac ctg gaa gct gaa caa cag aag ttg tgg aat gag gag 788

Leu Thr Lys Asp Leu Glu Ala Glu Gln Gln Lys Leu Trp Asn Glu Glu

195 200 205

tta aaa tat gcc aga ggc aaa gaa gcg att gaa aca caa tta gca gag 836

Leu Lys Tyr Ala Arg Gly Lys Glu Ala Ile Glu Thr Gln Leu Ala Glu

210 215 220

tat cac aaa ttg gct aga aaa tta aaa ctt att cct aaa ggt gct gag 884

Tyr His Lys Leu Ala Arg Lys Leu Lys Leu Ile Pro Lys Gly Ala Glu

225 230 235

aat tcc aaa ggt tat gac ttt gaa att aag ttt aat ccc gag gct ggt 932

Asn Ser Lys Gly Tyr Asp Phe Glu Ile Lys Phe Asn Pro Glu Ala Gly

240 245 250 255

gcc aac tgc ctt gtc aaa tac agg gct caa gtt tat gta cct ctt aag 980

Ala Asn Cys Leu Val Lys Tyr Arg Ala Gln Val Tyr Val Pro Leu Lys

260 265 270

gaa ctc ctg aat gaa act gaa gaa gaa att aat aaa gcc cta aat aaa 1028

Glu Leu Leu Asn Glu Thr Glu Glu Glu Ile Asn Lys Ala Leu Asn Lys

275 280 285

aaa atg ggt ttg gag gat act tta gaa caa ttg aat gca atg ata aca 1076

Lys Met Gly Leu Glu Asp Thr Leu Glu Gln Leu Asn Ala Met Ile Thr

290 295 300

gaa agc aag aga agt gtg gga act ctg aaa gaa gaa gtt caa aag ctg 1124

Glu Ser Lys Arg Ser Val Gly Thr Leu Lys Glu Glu Val Gln Lys Leu

305 310 315

gat gat ctt tac caa caa aaa att aag gaa gca gag gaa gag gat gaa 1172

Asp Asp Leu Tyr Gln Gln Lys Ile Lys Glu Ala Glu Glu Glu Asp Glu

320 325 330 335

aaa tgt gcc agt gag ctt gag tcc ttg gag aaa cac aag cac ctg cta 1220

Lys Cys Ala Ser Glu Leu Glu Ser Leu Glu Lys His Lys His Leu Leu

340 345 350

gaa agt act gtt aac cag ggg ctc agt gaa gct atg aat gaa tta gat 1268

Glu Ser Thr Val Asn Gln Gly Leu Ser Glu Ala Met Asn Glu Leu Asp

355 360 365

gct gtt cag cgg gaa tac caa cta gtt gtg caa acc acg act gaa gaa 1316

Ala Val Gln Arg Glu Tyr Gln Leu Val Val Gln Thr Thr Thr Glu Glu

370 375 380

aga cga aaa gtg gga aat aac ttg caa cgt ctg tta gag atg gtt gct 1364

Arg Arg Lys Val Gly Asn Asn Leu Gln Arg Leu Leu Glu Met Val Ala

385 390 395

aca cat gtt ggg tct gta gag aaa cat ctt gag gag cag att gct aaa 1412

Thr His Val Gly Ser Val Glu Lys His Leu Glu Glu Gln Ile Ala Lys

400 405 410 415

gtt gat aga gaa tat gaa gaa tgc atg tca gaa gat ctc tcg gaa aat 1460

Val Asp Arg Glu Tyr Glu Glu Cys Met Ser Glu Asp Leu Ser Glu Asn

420 425 430

att aaa gag att aga gat aag tat gag aag aaa gct act cta att aag 1508

Ile Lys Glu Ile Arg Asp Lys Tyr Glu Lys Lys Ala Thr Leu Ile Lys

435 440 445

tct tct gaa gaa tgaagataaa atgttgatca tgtatatata tccatagtga 1560

Ser Ser Glu Glu

450

ataaaattgt ctcagtaaag taaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaa 1613

<210> SEQ ID NO 43

<211> LENGTH: 78

<212> TYPE: PRT

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 43

Met Tyr Tyr Ile Leu Ile Tyr Pro Phe Pro Leu Phe Leu Phe Leu Leu

-20 -15 -10

Ser Leu Leu Ile Tyr Asn Gln Lys Met Lys Lys Ser Val His Leu Val

-5 -1 1 5 10

Phe Asp Leu Pro Lys His Leu Val Asn Leu Ile Phe Val Thr Leu Trp

15 20 25

Met Val Asn Leu Thr Phe Thr Gln Val Gly Phe Cys Phe Val Glu Asn

30 35 40

Asp Leu Leu Gly Gly Thr Thr Thr Thr Glu Arg Thr Lys Leu

45 50 55

<210> SEQ ID NO 44

<211> LENGTH: 234

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 44

atgtattata ttttaatcta tccttttcct ttgtttttgt tcttattatc tcttctgata 60

tataaccaaa aaatgaaaaa atctgtacac ttggtgtttg atttacctaa gcacctagtt 120

aatttaatct ttgtaacact ttggatggtt aacttaacct ttactcaagt tggtttttgt 180

tttgttgaaa atgacttact tggtggaacc actactactg aaagaacgaa actt 234

<210> SEQ ID NO 45

<211> LENGTH: 511

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<220> FEATURE:

<221> NAME/KEY: sig_peptide

<222> LOCATION: (49)..(114)

<221> NAME/KEY: mat_peptide

<222> LOCATION: (115)..(282)

<221> NAME/KEY: CDS

<222> LOCATION: (49)..(282)

<400> SEQUENCE: 45

attttatcaa ttgtttgtat ttccctttaa ggtaacattt taaatgaa atg tat tat 57

Met Tyr Tyr

-20

att tta atc tat cct ttt cct ttg ttt ttg ttc tta tta tct ctt ctg 105

Ile Leu Ile Tyr Pro Phe Pro Leu Phe Leu Phe Leu Leu Ser Leu Leu

-15 -10 -5

ata tat aac caa aaa atg aaa aaa tct gta cac ttg gtg ttt gat tta 153

Ile Tyr Asn Gln Lys Met Lys Lys Ser Val His Leu Val Phe Asp Leu

-1 1 5 10

cct aag cac cta gtt aat tta atc ttt gta aca ctt tgg atg gtt aac 201

Pro Lys His Leu Val Asn Leu Ile Phe Val Thr Leu Trp Met Val Asn

15 20 25

tta acc ttt act caa gtt ggt ttt tgt ttt gtt gaa aat gac tta ctt 249

Leu Thr Phe Thr Gln Val Gly Phe Cys Phe Val Glu Asn Asp Leu Leu

30 35 40 45

ggt gga acc act act act gaa aga acg aaa ctt tgatattaca ttgttaagta 302

Gly Gly Thr Thr Thr Thr Glu Arg Thr Lys Leu

50 55

tcagagctgt tacagagcaa gtccttttaa agagatgtaa aaattaagta cctgtgccaa 362

actgattttt attagaaacc ctgttttctt taagtaaaag tatattctac cagcatggct 422

tggtaagaaa aatcccctat ctttttttcc ctgtcctcaa aattcagaat ttttccggaa 482

aaaaaaaaaa aaaaaaaaaa aaaaaaaaa 511

<210> SEQ ID NO 46

<211> LENGTH: 73

<212> TYPE: PRT

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 46

Met Gln Phe Met Asn Leu Leu Val Gly Phe Ser Cys Ser Trp Gly Asn

-15 -10 -5 -1 1

Thr Cys Ala Cys His Thr Arg Pro Phe Leu Ala Pro Ser Val Phe Ser

5 10 15

Leu Cys Asp Gly Gly Leu Ile Val Ser Val Phe Thr Gln Gly Trp Phe

20 25 30

Pro Gly Cys Thr Ala Pro Val Pro Thr Pro Thr Val Pro Leu Ile Arg

35 40 45

Cys His Asp Phe Ser Ala Thr Ser Pro

50 55

<210> SEQ ID NO 47

<211> LENGTH: 219

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 47

atgcagttca tgaacttgct ggttggtttt tcctgctcct ggggtaacac atgcgcttgt 60

catacacgcc ccttccttgc cccttcagta ttctctcttt gcgatggagg tctcatagtg 120

agtgtcttca ctcaagggtg gtttcctggc tgcacggcac ctgttccaac acctactgtg 180

cctctcatca ggtgtcacga tttttctgcc acttcacct 219

<210> SEQ ID NO 48

<211> LENGTH: 903

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<220> FEATURE:

<221> NAME/KEY: sig_peptide

<222> LOCATION: (31)..(75)

<221> NAME/KEY: mat_peptide

<222> LOCATION: (76)..(249)

<221> NAME/KEY: CDS

<222> LOCATION: (31)..(249)

<400> SEQUENCE: 48

ggagtttcgt aagcaaaata gaggacagaa atg cag ttc atg aac ttg ctg gtt 54

Met Gln Phe Met Asn Leu Leu Val

-15 -10

ggt ttt tcc tgc tcc tgg ggt aac aca tgc gct tgt cat aca cgc ccc 102

Gly Phe Ser Cys Ser Trp Gly Asn Thr Cys Ala Cys His Thr Arg Pro

-5 -1 1 5

ttc ctt gcc cct tca gta ttc tct ctt tgc gat gga ggt ctc ata gtg 150

Phe Leu Ala Pro Ser Val Phe Ser Leu Cys Asp Gly Gly Leu Ile Val

10 15 20 25

agt gtc ttc act caa ggg tgg ttt cct ggc tgc acg gca cct gtt cca 198

Ser Val Phe Thr Gln Gly Trp Phe Pro Gly Cys Thr Ala Pro Val Pro

30 35 40

aca cct act gtg cct ctc atc agg tgt cac gat ttt tct gcc act tca 246

Thr Pro Thr Val Pro Leu Ile Arg Cys His Asp Phe Ser Ala Thr Ser

45 50 55

cct tagggagctt ccagtgattg attttaggag gcccacgcca agctccccag 299

Pro

gaaatgactg ccttccttgg gaccaaggac cgttccaacg gcattcactg ccagttctaa 359

taggcgagga aaatgcccga ggcgctgtct tctgtccccc acacgtacca gaaagtgaaa 419

aatgcagcga gtcctctggg cggttatgag cctccaggcg catgctgtcc agttggacgg 479

aacatctggc ggttggttga ttgctctctt ttgtcttggt cgctgcttct agaatctatg 539

caggggatag cagtgaggtc agaagtcttt cccgggagag agatggcctg ggttatcatt 599

gctgatagct ttggctgcat gagttgggct tccccttacc cagggctgca cagccaggtg 659

tgggggtcac cggcaggtgg gctggtggct gcagcctcag agccctccca ggttgctgct 719

gtttccagtg aatcacattt cgtcatttga agcccatgag gaccattgtg tggatccatg 779

gtgattctag acttcagata tatttaggaa ggcgcagatt tcaaatctgt gtttgatttt 839

ctgtaataag agaaatccaa tttgtaaaac ttgaaaaaaa aaaaaaaaaa aaaaaaaaaa 899

aaaa 903

<210> SEQ ID NO 49

<211> LENGTH: 421

<212> TYPE: PRT

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 49

Met Arg Trp Ile Leu Phe Ile Gly Ala Leu Ile Gly Ser Ser Ile Cys

-15 -10 -5 -1

Gly Gln Glu Lys Phe Phe Gly Asp Gln Val Phe Arg Ile Asn Val Arg

1 5 10 15

Asn Gly Asp Glu Ile Ser Lys Leu Ser Gln Leu Val Asn Ser Asn Asn

20 25 30

Leu Lys Leu Asn Phe Trp Lys Ser Pro Ser Ser Phe Asn Arg Pro Val

35 40 45

Asp Val Leu Val Pro Ser Val Ser Leu Gln Ala Phe Lys Ser Phe Leu

50 55 60

Arg Ser Gln Gly Leu Glu Tyr Ala Val Thr Ile Glu Asp Leu Gln Ala

65 70 75 80

Leu Leu Asp Asn Glu Asp Asp Glu Met Gln His Asn Glu Gly Gln Glu

85 90 95

Arg Ser Ser Asn Asn Phe Asn Tyr Gly Ala Tyr His Ser Leu Glu Ala

100 105 110

Thr Tyr His Glu Met Asp Asn Ile Ala Ala Asp Phe Pro Asp Leu Ala

115 120 125

Arg Arg Val Lys Ile Gly His Ser Phe Glu Asn Arg Thr Met Tyr Val

130 135 140

Leu Lys Phe Ser Thr Gly Lys Gly Val Arg Arg Pro Ala Val Trp Leu

145 150 155 160

Asn Ala Gly Ile His Ser Arg Glu Trp Ile Ser Gln Ala Thr Ala Ile

165 170 175

Trp Thr Ala Arg Lys Ile Val Ser Asp Tyr Gln Arg Asp Pro Ala Ile

180 185 190

Thr Ser Ile Leu Glu Lys Met Asp Ile Phe Leu Leu Pro Val Ala Asn

195 200 205

Pro Asp Gly Tyr Val Tyr Thr Gln Thr Gln Asn Arg Leu Trp Arg Lys

210 215 220

Thr Arg Ser Arg Asn Pro Gly Ser Ser Cys Ile Gly Ala Asp Pro Asn

225 230 235 240

Arg Asn Trp Asn Ala Ser Phe Ala Gly Lys Gly Ala Ser Asp Asn Pro

245 250 255

Cys Ser Glu Val Tyr His Gly Pro His Ala Asn Ser Glu Val Glu Val

260 265 270

Lys Ser Val Val Asp Phe Ile Gln Lys His Gly Asn Phe Lys Gly Phe

275 280 285

Ile Asp Leu His Ser Tyr Ser Gln Leu Leu Met Tyr Pro Tyr Gly Tyr

290 295 300

Ser Val Lys Lys Ala Pro Asp Ala Glu Glu Leu Asp Lys Val Ala Arg

305 310 315 320

Leu Ala Ala Lys Ala Leu Ala Ser Val Ser Gly Thr Glu Tyr Gln Val

325 330 335

Gly Pro Thr Cys Thr Thr Val Tyr Pro Ala Ser Gly Ser Ser Ile Asp

340 345 350

Trp Ala Tyr Asp Asn Gly Ile Lys Phe Ala Phe Thr Phe Glu Leu Arg

355 360 365

Asp Thr Gly Thr Tyr Gly Phe Leu Leu Pro Ala Asn Gln Ile Ile Pro

370 375 380

Thr Ala Glu Glu Thr Trp Leu Gly Leu Lys Thr Ile Met Glu His Val

385 390 395 400

Arg Asp Asn Leu Tyr

405

<210> SEQ ID NO 50

<211> LENGTH: 1263

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 50

atgaggtgga tactgttcat tggggccctt attgggtcca gcatctgtgg ccaagaaaaa 60

ttttttgggg accaagtttt taggattaat gtcagaaatg gagacgagat cagcaaattg 120

agtcaactag tgaattcaaa caacttgaag ctcaatttct ggaaatctcc ctcctccttc 180

aatcggcctg tggatgtcct ggtcccatct gtcagtctgc aggcatttaa atccttcctg 240

agatcccagg gcttagagta cgcagtgaca attgaggacc tgcaggccct tttagacaat 300

gaagatgatg aaatgcaaca caatgaaggg caagaacgga gcagtaataa cttcaactac 360

ggggcttacc attccctgga agctacttac cacgagatgg acaacattgc cgcagacttt 420

cctgacctgg cgaggagggt gaagattgga cattcgtttg aaaaccggac gatgtatgta 480

ctgaagttca gcactgggaa aggcgtgagg cggccggccg tttggctgaa tgcaggcatc 540

cattcccgag agtggatctc ccaggccact gcaatctgga cggcaaggaa gattgtatct 600

gattaccaga gggatccagc tatcacctcc atcttggaga aaatggatat tttcttgttg 660

cctgtggcca atcctgatgg atatgtgtat actcaaactc aaaaccgatt atggaggaag 720

acgcggtccc gaaatcctgg aagctcctgc attggtgctg acccaaatag aaactggaac 780

gctagttttg caggaaaggg agccagcgac aacccttgct ccgaagtgta ccatggaccc 840

cacgccaatt cggaagtgga ggtgaaatca gtggtagatt tcatccaaaa acatgggaat 900

ttcaagggct tcatcgacct gcacagctac tcgcagctgc tgatgtatcc atatgggtac 960

tcagtcaaaa aggccccaga tgccgaggaa ctcgacaagg tggcgaggct tgcggccaaa 1020

gctctggctt ctgtgtcggg cactgagtac caagtgggtc ccacctgcac cactgtctat 1080

ccagctagcg ggagcagcat cgactgggcg tatgacaacg gcatcaaatt tgcattcaca 1140

tttgagttga gagataccgg gacctatggc ttcctcctgc cagctaacca gatcatcccc 1200

actgcagagg agacgtggct ggggctgaag accatcatgg agcatgtgcg ggacaacctc 1260

tac 1263

<210> SEQ ID NO 51

<211> LENGTH: 2796

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<220> FEATURE:

<221> NAME/KEY: sig_peptide

<222> LOCATION: (11)..(58)

<221> NAME/KEY: mat_peptide

<222> LOCATION: (59)..(1273)

<221> NAME/KEY: CDS

<222> LOCATION: (11)..(1273)

<400> SEQUENCE: 51

ccccggggac atg agg tgg ata ctg ttc att ggg gcc ctt att ggg tcc 49

Met Arg Trp Ile Leu Phe Ile Gly Ala Leu Ile Gly Ser

-15 -10 -5

agc atc tgt ggc caa gaa aaa ttt ttt ggg gac caa gtt ttt agg att 97

Ser Ile Cys Gly Gln Glu Lys Phe Phe Gly Asp Gln Val Phe Arg Ile

-1 1 5 10

aat gtc aga aat gga gac gag atc agc aaa ttg agt caa cta gtg aat 145

Asn Val Arg Asn Gly Asp Glu Ile Ser Lys Leu Ser Gln Leu Val Asn

15 20 25

tca aac aac ttg aag ctc aat ttc tgg aaa tct ccc tcc tcc ttc aat 193

Ser Asn Asn Leu Lys Leu Asn Phe Trp Lys Ser Pro Ser Ser Phe Asn

30 35 40 45

cgg cct gtg gat gtc ctg gtc cca tct gtc agt ctg cag gca ttt aaa 241

Arg Pro Val Asp Val Leu Val Pro Ser Val Ser Leu Gln Ala Phe Lys

50 55 60

tcc ttc ctg aga tcc cag ggc tta gag tac gca gtg aca att gag gac 289

Ser Phe Leu Arg Ser Gln Gly Leu Glu Tyr Ala Val Thr Ile Glu Asp

65 70 75

ctg cag gcc ctt tta gac aat gaa gat gat gaa atg caa cac aat gaa 337

Leu Gln Ala Leu Leu Asp Asn Glu Asp Asp Glu Met Gln His Asn Glu

80 85 90

ggg caa gaa cgg agc agt aat aac ttc aac tac ggg gct tac cat tcc 385

Gly Gln Glu Arg Ser Ser Asn Asn Phe Asn Tyr Gly Ala Tyr His Ser

95 100 105

ctg gaa gct act tac cac gag atg gac aac att gcc gca gac ttt cct 433

Leu Glu Ala Thr Tyr His Glu Met Asp Asn Ile Ala Ala Asp Phe Pro

110 115 120 125

gac ctg gcg agg agg gtg aag att gga cat tcg ttt gaa aac cgg acg 481

Asp Leu Ala Arg Arg Val Lys Ile Gly His Ser Phe Glu Asn Arg Thr

130 135 140

atg tat gta ctg aag ttc agc act ggg aaa ggc gtg agg cgg ccg gcc 529

Met Tyr Val Leu Lys Phe Ser Thr Gly Lys Gly Val Arg Arg Pro Ala

145 150 155

gtt tgg ctg aat gca ggc atc cat tcc cga gag tgg atc tcc cag gcc 577

Val Trp Leu Asn Ala Gly Ile His Ser Arg Glu Trp Ile Ser Gln Ala

160 165 170

act gca atc tgg acg gca agg aag att gta tct gat tac cag agg gat 625

Thr Ala Ile Trp Thr Ala Arg Lys Ile Val Ser Asp Tyr Gln Arg Asp

175 180 185

cca gct atc acc tcc atc ttg gag aaa atg gat att ttc ttg ttg cct 673

Pro Ala Ile Thr Ser Ile Leu Glu Lys Met Asp Ile Phe Leu Leu Pro

190 195 200 205

gtg gcc aat cct gat gga tat gtg tat act caa act caa aac cga tta 721

Val Ala Asn Pro Asp Gly Tyr Val Tyr Thr Gln Thr Gln Asn Arg Leu

210 215 220

tgg agg aag acg cgg tcc cga aat cct gga agc tcc tgc att ggt gct 769

Trp Arg Lys Thr Arg Ser Arg Asn Pro Gly Ser Ser Cys Ile Gly Ala

225 230 235

gac cca aat aga aac tgg aac gct agt ttt gca gga aag gga gcc agc 817

Asp Pro Asn Arg Asn Trp Asn Ala Ser Phe Ala Gly Lys Gly Ala Ser

240 245 250

gac aac cct tgc tcc gaa gtg tac cat gga ccc cac gcc aat tcg gaa 865

Asp Asn Pro Cys Ser Glu Val Tyr His Gly Pro His Ala Asn Ser Glu

255 260 265

gtg gag gtg aaa tca gtg gta gat ttc atc caa aaa cat ggg aat ttc 913

Val Glu Val Lys Ser Val Val Asp Phe Ile Gln Lys His Gly Asn Phe

270 275 280 285

aag ggc ttc atc gac ctg cac agc tac tcg cag ctg ctg atg tat cca 961

Lys Gly Phe Ile Asp Leu His Ser Tyr Ser Gln Leu Leu Met Tyr Pro

290 295 300

tat ggg tac tca gtc aaa aag gcc cca gat gcc gag gaa ctc gac aag 1009

Tyr Gly Tyr Ser Val Lys Lys Ala Pro Asp Ala Glu Glu Leu Asp Lys

305 310 315

gtg gcg agg ctt gcg gcc aaa gct ctg gct tct gtg tcg ggc act gag 1057

Val Ala Arg Leu Ala Ala Lys Ala Leu Ala Ser Val Ser Gly Thr Glu

320 325 330

tac caa gtg ggt ccc acc tgc acc act gtc tat cca gct agc ggg agc 1105

Tyr Gln Val Gly Pro Thr Cys Thr Thr Val Tyr Pro Ala Ser Gly Ser

335 340 345

agc atc gac tgg gcg tat gac aac ggc atc aaa ttt gca ttc aca ttt 1153

Ser Ile Asp Trp Ala Tyr Asp Asn Gly Ile Lys Phe Ala Phe Thr Phe

350 355 360 365

gag ttg aga gat acc ggg acc tat ggc ttc ctc ctg cca gct aac cag 1201

Glu Leu Arg Asp Thr Gly Thr Tyr Gly Phe Leu Leu Pro Ala Asn Gln

370 375 380

atc atc ccc act gca gag gag acg tgg ctg ggg ctg aag acc atc atg 1249

Ile Ile Pro Thr Ala Glu Glu Thr Trp Leu Gly Leu Lys Thr Ile Met

385 390 395

gag cat gtg cgg gac aac ctc tac taggcgatgg ctctgctctg tctacattta 1303

Glu His Val Arg Asp Asn Leu Tyr

400 405

tttgtaccca cacgtgcacg cactgaggcc attgttaaag gagctctttc ctacctgtgt 1363

gagtcagagc cctctgggtt tgtggagcac acaggcctgc ccctctccag ccagctccct 1423

ggagtcgtgt gtcctggcgg tgtccctgca agaactggtt ctgccagcct gctcaatttt 1483

ggtcctgctg tttttgatga gccttttgtc tgtttctcct tccaccctgc tggctgggcg 1543

gctgcactca gcatcacccc ttcctgggtg gcatgtctct ctctacctca tttttagaac 1603

caaagaacat ctgagatgat tctctaccct catccacatc tagccaagcc agtgaccttg 1663

ctctggtggc actgtgggag acaccacttg tctttaggtg ggtctcaaag atgatgtaga 1723

atttccttta atttctcgca gtcttcctgg aaaatatttt cctttgagca gcaaatcttg 1783

tagggatatc agtgaaggtc tctccctccc tcctctcctg tttttttttt tgagacagag 1843

ttttgctctt gttgcccaga ctggagtgtg atggctcgac cttggctcac cacaacctct 1903

gcctcctggg ttcaagcaat tctcctgcct cagcctcttg agtagcttgg tttataggcg 1963

catgccacca tgcctggcta attttgtgtt tttagtagag acagggtttc tccatgttgg 2023

tcaggctggt ctcaaactcc caacctcagg tgatctgccc tccttggcct cccagagtgc 2083

tgggattaca ggtgtgagcc actgtgccgg tcccgtcccc tcctttttta ggcctgaata 2143

caaagtagaa gatcactttc cttcactgtg ctgagaattt ctagatacta cagttcttac 2203

tcctctcttc cctttgttat tcagtgtgac caggatggcg ggaggggatc tgtgtcactg 2263

taggtactgt gcccaggaag gctgggtgaa gtgaccatct aaattgcagg atggtgaaat 2323

tatccccatc tgtcctaatg ggcttacctc ctctttgcct tttgaactca cttcaaagat 2383

ctaggcctca tcttacaggt cctaaatcac tcatctggcc tggataatct cactgccctg 2443

gcacattccc atttgtgctg tggtgtatcc tgtgtttcct tgtcctggtt tgtgtgtgtg 2503

tgtgtgtgtg tgtgtgtgtg tgtgtgtgtt tgtgtgtgtg tgtctgtcta ttttgtatcc 2563

tggaccacaa gttcctaagt agagcaagaa ttcatcaacc agctgcctct tgtttcattt 2623

cacctcagca cgtaccatct gtccttttgt tgttgttgtt ttgtttttgt ttttttgctt 2683

ttaccaaaca tgtctgtaaa tcttaacctc ctgcctagga tttgtacagc atctggtgtg 2743

tgcttataag ccaataaata ttcaatgtca aaaaaaaaaa aaaaaaaaaa aaa 2796

<210> SEQ ID NO 52

<211> LENGTH: 111

<212> TYPE: PRT

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 52

Met Leu Ile Ile Val Leu Val Asn Ala Phe Val Ser Ile Thr Val Glu

-10 -5 -1 1

Asn Phe Phe Leu Asp Met Val Leu Trp Lys Val Val Phe Asn Arg Asp

5 10 15

Lys Gln Gly Glu Tyr Arg Phe Ser Thr Thr Gln Pro Pro Gln Glu Ser

20 25 30

Val Asp Arg Trp Gly Lys Cys Cys Leu Pro Trp Ala Leu Gly Cys Arg

35 40 45 50

Lys Lys Thr Pro Lys Ala Lys Tyr Met Tyr Leu Ala Gln Glu Leu Leu

55 60 65

Val Asp Pro Glu Trp Pro Pro Lys Pro Gln Thr Thr Thr Glu Ala Lys

70 75 80

Ala Leu Val Lys Glu Asn Gly Ser Cys Gln Ile Ile Thr Ile Thr

85 90 95

<210> SEQ ID NO 53

<211> LENGTH: 333

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 53

atgctcatca ttgttcttgt caatgccttt gtgtctatca cagtggagaa cttcttcctt 60

gacatggtcc tttggaaagt tgtgttcaac cgagacaaac aaggagagta tcggttcagc 120

accacacagc caccgcagga gtcagtggat cggtggggaa aatgctgctt accctgggcc 180

ctgggctgta gaaagaagac accaaaggca aagtacatgt atctggcgca ggagctcttg 240

gttgatccag aatggccacc aaaacctcag acaaccacag aagctaaagc tttagttaag 300

gagaatggat catgtcaaat catcaccata aca 333

<210> SEQ ID NO 54

<211> LENGTH: 3635

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<220> FEATURE:

<221> NAME/KEY: sig_peptide

<222> LOCATION: (36)..(77)

<221> NAME/KEY: mat_peptide

<222> LOCATION: (78)..(368)

<221> NAME/KEY: CDS

<222> LOCATION: (36)..(368)

<400> SEQUENCE: 54

agatagtgtg tgtaccatat cagtggcgtg taact atg ctc atc att gtt ctt 53

Met Leu Ile Ile Val Leu

-10

gtc aat gcc ttt gtg tct atc aca gtg gag aac ttc ttc ctt gac atg 101

Val Asn Ala Phe Val Ser Ile Thr Val Glu Asn Phe Phe Leu Asp Met

-5 -1 1 5

gtc ctt tgg aaa gtt gtg ttc aac cga gac aaa caa gga gag tat cgg 149

Val Leu Trp Lys Val Val Phe Asn Arg Asp Lys Gln Gly Glu Tyr Arg

10 15 20

ttc agc acc aca cag cca ccg cag gag tca gtg gat cgg tgg gga aaa 197

Phe Ser Thr Thr Gln Pro Pro Gln Glu Ser Val Asp Arg Trp Gly Lys

25 30 35 40

tgc tgc tta ccc tgg gcc ctg ggc tgt aga aag aag aca cca aag gca 245

Cys Cys Leu Pro Trp Ala Leu Gly Cys Arg Lys Lys Thr Pro Lys Ala

45 50 55

aag tac atg tat ctg gcg cag gag ctc ttg gtt gat cca gaa tgg cca 293

Lys Tyr Met Tyr Leu Ala Gln Glu Leu Leu Val Asp Pro Glu Trp Pro

60 65 70

cca aaa cct cag aca acc aca gaa gct aaa gct tta gtt aag gag aat 341

Pro Lys Pro Gln Thr Thr Thr Glu Ala Lys Ala Leu Val Lys Glu Asn

75 80 85

gga tca tgt caa atc atc acc ata aca tagcagtgaa tcagtctcag 388

Gly Ser Cys Gln Ile Ile Thr Ile Thr

90 95

tggtattgct gatagcagta ttcaggaata tgtgatttta ggagtttctg atcctgtgtg 448

tcagaatggc actagttcag tttatgtccc ttctgatata gtagcttatt tgacagcttt 508

gctcttcctt aaaataaaaa cagaaaaata tatcgtccta acagttaaat taacaatcaa 568

tccataaagt cctatatctt cattcagcaa cccaaatatt acatacattt ccagaatttt 628

cttgattgtt actttcagtg atattcttta tattgggtac aggagaagtt tggtgtttgg 688

taggtttttc aacattagtt tttgagacta gtttacctct tcacatttat gctcacaacc 748

ctcttgttag aaaagtctgt gtttatatac aggctgtaag tttgtgattg ataaaaagaa 808

gatgagtgtt aattagcctc cagtgaaaat atactgaaag cctgttttca tttgattcca 868

atgtttcttc caaagaattc tgtataaaca tatgccaatt ccctatgatg gtctagagtt 928

aggaatgagt gtttatggtg ttgcttatag aacaactcag gtaatctcca tttctggttt 988

tatattttct gtacaaactg cctgggtttt atttttctaa tcagcaaggt gcttcactgc 1048

cttcttgaga cgcctctcaa agctcttaaa tggctcctgt gctatgtgtg gtgttggcag 1108

tctaatttgc ttctgttaaa tgttgtagaa cctttttcac taggaaataa gattcatttc 1168

tttcggcagt agatgtagat tcatctttta acgtttcttc aaatttgttt ctgtcaggct 1228

ttgtgttatt ttaaatggtt ttttaaaatt ttcttctatg ttttcaatta cctaaagaca 1288

taggataata gtttttttta agttagaatt ttacctcata aaattttttg aggtttgatg 1348

tatgtctctg tcttatcaat aatgaggctt aaaaaatact ggatttgaat ggctgccgtt 1408

ttttcaaagc aatatgaatt tgatgagttt gttttatgcc attaggtggc gccagaggtc 1468

agaacatgtc tattttgaat tggatcgtta caaatgagca tatttgatgc ggaaatttct 1528

gggagaaaaa aaattgagga aataaagtta aaaaattgac attcattgag ccaaaagaga 1588

tgtggagaaa catttttcac ctttctgttt ggcctgatta acatttaaat tcttgccaaa 1648

attaaggtaa cttttaaaaa caccttttat aggtggatcc agcagtctgg caacgcccac 1708

agttaccaca acacagaaaa ctgatcgtgc tataaaatgg acgctaaact atgaaaacag 1768

tgtgacattg ttctctgttc ttccagagcc agtaacatgc ttgctcgtgc tttctacttc 1828

tagctgatca ttcttttccc aacatatatt tacaaattta ccaaatttta cctagaattt 1888

taggaccaaa tggttctcac tctttatgct gcaaagacct ggatgatgtt tggtaactat 1948

agaaaaatag aaattacact caggatcact gttactgcta ttgccactga tgattcctgc 2008

aaaatataat cgaagttttc catcaaatgt ataatatgct attaatacac attagatgat 2068

aacagttgtt ccatgaatga ttctatgaag ctatgcatct tagacctctt gagctgtgaa 2128

ttagcactat tttctatagt tacttattct ctggatcatt ttataatttc catattaatt 2188

tcaaatatgc tcgtgttatt cttcagtgat ttccacaatt gtgcatttta ttctttggtt 2248

taagtactga agcatataat gaaagtaatt gctaagtagc agcttaaaaa ttcaattatc 2308

cgattgtatt taacatcttt aagagcatga tcataaagag ctatttttga cacccccccc 2368

cactttttta acatttagag ttaataaggg ttttatatct cttctgtcca tattgttttc 2428

aaaggaatga ggtgtttagg tggctggaaa agcatttgta ggaagttaga tttgaatata 2488

gacaaggtgg gttattcacg ttgagaatgt tatttgaaga atgcctgtga agccaggtgt 2548

gggttctact cagtgccata gatagactga gtcttctctc gtaggtcacc attacatagt 2608

aattttgatt ctgaatttca cattaaatta tttgagttta tacagaccta aattttaaaa 2668

tctgtacata tattattttg atgtattaag atgaatattg ctgatttaaa ttttatttat 2728

gcacatactt aaaggacaga aatgtctggg aaagtaattg ttaaataatg atatgtaact 2788

ttttaacttt ttaaataaat aacaagattt ttaatgtgtg tctccctcag ggttgtttaa 2848

agtttttttt ctccctcaag tataaatagt ggtaactata tgttttgtat cttctagcac 2908

caactgctgt aaagcaatgc tgcaaataat gcttgaatac aagtggctaa gccaacaaca 2968

gaataaatac ttttatagta gttttataat cctgaaattc gaaagctttc ccaattgcac 3028

ttgcatctaa acaaaactgt tgcagttttt actctattta ttttgttccc catgtttatg 3088

aaagtcctgc acagtttcaa aggcatggta aataatatat caatgtttat gtagtctgtt 3148

acagaaacag ctatagataa cattatccag tgaagagcaa aattcaagct ttagaaaata 3208

ttcatgcatg caattttgac atatctaaaa ataggttttt gtatatttat ggtgggaggt 3268

ggttgggaac ttttaacaaa atggggtgtt aatttttgta cagtctgtgg gcatttacac 3328

atttttaatg tattaaaatt tggtaattat gtgtacatta aattaataaa agttacttct 3388

agttatgatt tgtgaattcc ctaagacctt ggattttttt aagtaacttt atatcagaaa 3448

tgatactgca tctttatatt tttaaaattg tattgctgct caagaatggt accctcttgt 3508

caaaaaggca tacattcata attgtacatt cagcattgta aataatctta tgaaaccttt 3568

tttgattgaa gctattcaaa ataaaaattt taatgaacga aaaaaaaaaa aaaaaaaaaa 3628

aaaaaaa 3635

<210> SEQ ID NO 55

<211> LENGTH: 1109

<212> TYPE: PRT

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 55

Met Leu Ile Glu His Pro Leu Arg Cys Leu Val Leu Cys Ala Gln Val

-15 -10 -5

His Ala Gly Met Trp Arg Arg Asn Gly Phe Ser Leu Val Asn Gln Ile

-1 1 5 10

Tyr Tyr Tyr His Asn Val Lys Cys Arg Arg Glu Met Phe Asp Lys Asp

15 20 25 30

Val Val Met Leu Gln Thr Gly Val Ser Met Met Asp Pro Asn His Phe

35 40 45

Leu Met Ile Met Leu Ser Arg Phe Glu Leu Tyr Gln Ile Phe Ser Thr

50 55 60

Pro Asp Tyr Gly Lys Arg Phe Ser Ser Glu Ile Thr His Lys Asp Val

65 70 75

Val Gln Gln Asn Asn Thr Leu Ile Glu Glu Met Leu Tyr Leu Ile Ile

80 85 90

Met Leu Val Gly Glu Arg Phe Ser Pro Gly Val Gly Gln Val Asn Ala

95 100 105 110

Thr Asp Glu Ile Lys Arg Glu Ile Ile His Gln Leu Ser Ile Lys Pro

115 120 125

Met Ala His Ser Glu Leu Val Lys Ser Leu Pro Glu Asp Glu Asn Lys

130 135 140

Glu Thr Gly Met Glu Ser Val Ile Glu Ala Val Ala His Phe Lys Lys

145 150 155

Pro Gly Leu Thr Gly Arg Gly Met Tyr Glu Leu Lys Pro Glu Cys Ala

160 165 170

Lys Glu Phe Asn Leu Tyr Phe Tyr His Phe Ser Arg Ala Glu Gln Ser

175 180 185 190

Lys Ala Glu Glu Ala Gln Arg Lys Leu Lys Arg Gln Asn Arg Glu Asp

195 200 205

Thr Ala Leu Pro Pro Pro Val Leu Pro Pro Phe Cys Pro Leu Phe Ala

210 215 220

Ser Leu Val Asn Ile Leu Gln Ser Asp Val Met Leu Cys Ile Met Gly

225 230 235

Thr Ile Leu Gln Trp Ala Val Glu His Asn Gly Tyr Ala Trp Ser Glu

240 245 250

Ser Met Leu Gln Arg Val Leu His Leu Ile Gly Met Ala Leu Gln Glu

255 260 265 270

Glu Lys Gln His Leu Glu Asn Val Thr Glu Glu His Val Val Thr Phe

275 280 285

Thr Phe Thr Gln Lys Ile Ser Lys Pro Gly Glu Ala Pro Lys Asn Ser

290 295 300

Pro Ser Ile Leu Ala Met Leu Glu Thr Leu Gln Asn Ala Pro Tyr Leu

305 310 315

Glu Val His Lys Asp Met Ile Arg Trp Ile Leu Lys Thr Phe Asn Ala

320 325 330

Val Lys Lys Met Arg Glu Ser Ser Pro Thr Ser Pro Val Ala Glu Thr

335 340 345 350

Glu Gly Thr Ile Met Glu Glu Ser Ser Arg Asp Lys Asp Lys Ala Glu

355 360 365

Arg Lys Arg Lys Ala Glu Ile Ala Arg Leu Arg Arg Glu Lys Ile Met

370 375 380

Ala Gln Met Ser Glu Met Gln Arg His Phe Ile Asp Glu Asn Lys Glu

385 390 395

Leu Phe Gln Gln Thr Leu Glu Leu Asp Ala Ser Thr Ser Ala Val Leu

400 405 410

Asp His Ser Pro Val Ala Ser Asp Met Thr Leu Thr Ala Leu Gly Pro

415 420 425 430

Ala Gln Thr Gln Val Pro Glu Gln Arg Gln Phe Val Thr Cys Ile Leu

435 440 445

Cys Gln Glu Glu Gln Glu Val Lys Val Glu Ser Arg Ala Met Val Leu

450 455 460

Ala Ala Phe Val Gln Arg Ser Thr Val Leu Ser Lys Asn Arg Ser Lys

465 470 475

Phe Ile Gln Asp Pro Glu Lys Tyr Asp Pro Leu Phe Met His Pro Asp

480 485 490

Leu Ser Cys Gly Thr His Thr Ser Ser Cys Gly His Ile Met His Ala

495 500 505 510

His Cys Trp Gln Arg Tyr Phe Asp Ser Val Gln Ala Lys Glu Gln Arg

515 520 525

Arg Gln Gln Arg Leu Arg Leu His Thr Ser Tyr Asp Val Glu Asn Gly

530 535 540

Glu Phe Leu Cys Pro Leu Cys Glu Cys Leu Ser Asn Thr Val Ile Pro

545 550 555

Leu Leu Leu Ser Pro Arg Asn Ile Phe Asn Asn Arg Leu Asn Phe Ser

560 565 570

Asp Gln Pro Asn Leu Thr Gln Trp Ile Arg Thr Ile Ser Gln Gln Ile

575 580 585 590

Lys Ala Leu Gln Phe Leu Arg Lys Glu Glu Ser Thr Pro Asn Asn Ala

595 600 605

Ser Thr Lys Asn Ser Glu Asn Val Asp Glu Leu Gln Leu Pro Glu Gly

610 615 620

Phe Arg Pro Asp Phe Arg Pro Lys Ile Pro Tyr Ser Glu Ser Ile Lys

625 630 635

Glu Met Leu Thr Thr Phe Gly Thr Ala Thr Tyr Lys Val Gly Leu Lys

640 645 650

Val His Pro Asn Glu Glu Asp Pro Arg Val Pro Ile Met Cys Trp Gly

655 660 665 670

Ser Cys Ala Tyr Thr Ile Gln Ser Ile Glu Arg Ile Leu Ser Asp Glu

675 680 685

Asp Lys Pro Leu Phe Gly Pro Leu Pro Cys Arg Leu Asp Asp Cys Leu

690 695 700

Arg Ser Leu Thr Arg Phe Ala Ala Ala His Trp Thr Val Ala Ser Val

705 710 715

Ser Val Val Gln Gly His Phe Cys Lys Leu Phe Ala Ser Leu Val Pro

720 725 730

Asn Asp Ser His Glu Glu Leu Pro Cys Ile Leu Asp Ile Asp Met Phe

735 740 745 750

His Leu Leu Val Gly Leu Val Leu Ala Phe Pro Ala Leu Gln Cys Gln

755 760 765

Asp Phe Ser Gly Ile Ser Leu Gly Thr Gly Asp Leu His Ile Phe His

770 775 780

Leu Val Thr Met Ala His Ile Ile Gln Ile Leu Leu Thr Ser Cys Thr

785 790 795

Glu Glu Asn Gly Met Asp Gln Glu Asn Pro Pro Cys Glu Glu Glu Ser

800 805 810

Ala Val Leu Ala Leu Tyr Lys Thr Leu His Gln Tyr Thr Gly Ser Ala

815 820 825 830

Leu Lys Glu Ile Pro Ser Gly Trp His Leu Trp Arg Ser Val Arg Ala

835 840 845

Gly Ile Met Pro Phe Leu Lys Cys Ser Ala Leu Phe Phe His Tyr Leu

850 855 860

Asn Gly Val Pro Ser Pro Pro Asp Ile Gln Val Pro Gly Thr Ser His

865 870 875

Phe Glu His Leu Cys Ser Tyr Leu Ser Leu Pro Asn Asn Leu Ile Cys

880 885 890

Leu Phe Gln Glu Asn Ser Glu Ile Met Asn Ser Leu Ile Glu Ser Trp

895 900 905 910

Cys Arg Asn Ser Glu Val Lys Arg Tyr Leu Glu Gly Glu Arg Asp Ala

915 920 925

Ile Arg Tyr Pro Arg Glu Ser Asn Lys Leu Ile Asn Leu Pro Glu Asp

930 935 940

Tyr Ser Ser Leu Ile Asn Gln Ala Ser Asn Phe Ser Cys Pro Lys Ser

945 950 955

Gly Gly Asp Lys Ser Arg Ala Pro Thr Leu Cys Leu Val Cys Gly Ser

960 965 970

Leu Leu Cys Ser Gln Ser Tyr Cys Cys Gln Thr Glu Leu Glu Gly Glu

975 980 985 990

Asp Val Gly Ala Cys Thr Ala His Thr Tyr Ser Cys Gly Ser Gly Val

995 1000 1005

Gly Ile Phe Leu Arg Val Arg Glu Cys Gln Val Leu Phe Leu Ala Gly

1010 1015 1020

Lys Thr Lys Gly Cys Phe Tyr Ser Pro Pro Tyr Leu Asp Asp Tyr Gly

1025 1030 1035

Glu Thr Asp Gln Gly Leu Arg Arg Gly Asn Pro Leu His Leu Cys Lys

1040 1045 1050

Glu Arg Phe Lys Lys Ile Gln Lys Leu Trp His Gln His Ser Val Thr

1055 1060 1065 1070

Glu Glu Ile Gly His Ala Gln Glu Ala Asn Gln Thr Leu Val Gly Ile

1075 1080 1085

Asp Trp Gln His Leu

1090

<210> SEQ ID NO 56

<211> LENGTH: 3327

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 56

atgttgatag aacaccctct tagatgtctt gttctgtgtg cccaagtaca tgccggaatg 60

tggagaagaa atgggttctc tctagtaaac cagatttatt actaccataa tgtgaaatgc 120

agacgtgaga tgtttgacaa ggatgtagta atgcttcaga caggtgtctc catgatggat 180

ccaaatcatt tcctgatgat catgctcagc cgctttgaac tttatcagat tttcagtact 240

ccagactatg gaaaaagatt tagttctgag attacccata aggatgttgt tcagcagaac 300

aatactctaa tagaagaaat gctatacctc attataatgc ttgttggaga gagatttagt 360

cctggagttg gacaggtaaa tgctacagat gaaatcaagc gagagattat ccatcagttg 420

agtatcaagc ctatggctca tagtgaattg gtaaagtctt tacctgaaga tgagaacaag 480

gagactggca tggagagtgt aatcgaagca gttgcccatt tcaagaaacc tggattaaca 540

ggacgaggca tgtatgaact gaaaccagaa tgtgccaaag agttcaactt gtatttctat 600

cacttttcaa gggcagaaca gtccaaggca gaagaagcgc aacggaaatt gaaaagacaa 660

aatagagaag atacagcact cccacctccg gtgttgcctc cattctgccc tctgtttgca 720

agcctggtta acattttgca gtcagatgtc atgttgtgca tcatgggaac aattctgcaa 780

tgggctgtgg aacataatgg atatgcctgg tcagagtcca tgctgcaaag ggtgttacat 840

ttaattggca tggcactaca agaagaaaaa caacatttag agaatgtcac ggaagagcat 900

gtagtaacat ttaccttcac tcagaagata tcaaaacctg gtgaagcgcc aaaaaattct 960

cctagcatac tagctatgct ggaaacacta caaaatgctc cctacctaga agtccacaaa 1020

gacatgattc ggtggatatt gaagactttt aatgctgtta aaaagatgag ggagagttca 1080

cctaccagtc ccgtggcaga gacagaagga accataatgg aagagagttc aagggacaaa 1140

gacaaagctg agaggaagag aaaagcagag attgccagac tgcgcagaga aaagatcatg 1200

gctcagatgt ctgaaatgca gcggcatttt attgatgaaa acaaagaact ctttcagcag 1260

acattagaac tggatgcctc aacctctgct gttcttgatc atagccctgt ggcttcagat 1320

atgacactta cagcactggg ccccgcacaa actcaggttc ctgaacaaag acaattcgtt 1380

acatgtatat tgtgtcaaga ggagcaagaa gttaaagtgg aaagcagggc aatggtcttg 1440

gcagcatttg ttcagagatc aactgtatta tcaaaaaaca gaagtaaatt tattcaagat 1500

ccagaaaaat atgatccatt attcatgcac cctgatctgt cttgtggaac acacactagt 1560

agctgtgggc acattatgca tgcccattgt tggcaaaggt attttgattc cgttcaagct 1620

aaagaacagc gaaggcaaca gagattacgc ttacatacga gctatgatgt agaaaacgga 1680

gaattccttt gccccctttg tgaatgcttg agtaatactg ttattcctct gctgctttct 1740

ccaagaaata tttttaacaa caggttaaat ttttcagacc aaccaaatct gactcagtgg 1800

attagaacaa tatctcagca aataaaagca ttacagtttc ttaggaaaga agaaagtact 1860

cctaataatg cctctacaaa gaattcagaa aatgtggatg aattacagct ccctgaaggg 1920

ttcaggcctg attttcgtcc taagatccct tattctgaga gcataaaaga aatgctaacg 1980

acatttggaa ctgctaccta caaggtggga ctaaaggttc atcccaatga agaggatcct 2040

cgtgttccca taatgtgttg gggtagctgc gcgtacacca tccaaagcat agaaagaatt 2100

ttgagtgatg aagataaacc attgtttggt cctttacctt gcagactgga tgactgtctt 2160

aggtcattga cgagatttgc cgcagcacac tggacagtgg catcagtttc agtggtgcaa 2220

ggacattttt gtaaactttt tgcatcactg gtgcctaatg acagccatga ggaacttcca 2280

tgcatattag atattgacat gtttcattta ttggtgggct tggtgcttgc atttcctgcg 2340

ttgcagtgtc aggatttttc agggatcagc cttggcactg gagaccttca cattttccat 2400

ctggttacta tggcacacat catacagatc ttacttacct catgtacaga agagaatggc 2460

atggatcaag aaaatccccc ttgtgaagaa gaatcagcag ttcttgcttt gtataaaaca 2520

cttcaccagt atacgggaag tgccttgaaa gaaataccat ccggctggca tctgtggagg 2580

agtgtcagag ctggaatcat gcctttcctg aagtgttctg ctttattttt tcattactta 2640

aatggagttc cttccccacc cgacattcaa gttcctggaa caagccattt tgaacattta 2700

tgtagctatc tttccctacc aaacaacctc atttgccttt ttcaagaaaa tagtgagata 2760

atgaattcac tgattgaaag ttggtgccgt aacagtgaag ttaaaagata tctagaaggt 2820

gaaagagatg ctataagata tccaagagaa tctaacaaat taataaacct tccagaggat 2880

tacagcagcc tcattaatca agcatccaat ttctcgtgcc cgaaatcagg tggtgataag 2940

agcagagccc caactctgtg ccttgtgtgc ggatctctgc tgtgctccca gagttactgc 3000

tgccagactg aactggaagg ggaggatgta ggagcctgca cagctcacac ctactcctgt 3060

ggctctggag tgggcatctt cctgagagta cgggaatgtc aggtgctatt tttagctggc 3120

aaaaccaaag gctgttttta ttctcctcct taccttgatg actatgggga gaccgaccag 3180

ggactcagac ggggaaatcc tttacattta tgcaaagagc gattcaagaa gattcagaag 3240

ctctggcacc aacacagtgt cacagaggaa attggacatg cacaggaagc caatcagaca 3300

ctggttggca ttgactggca acattta 3327

<210> SEQ ID NO 57

<211> LENGTH: 3502

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<220> FEATURE:

<221> NAME/KEY: sig_peptide

<222> LOCATION: (56)..(109)

<221> NAME/KEY: mat_peptide

<222> LOCATION: (110)..(3382)

<221> NAME/KEY: CDS

<222> LOCATION: (56)..(3382)

<400> SEQUENCE: 57

tttttgtttt ctgttttttt attttttgta tatatagagt gaacttagcc caccc atg 58

Met

ttg ata gaa cac cct ctt aga tgt ctt gtt ctg tgt gcc caa gta cat 106

Leu Ile Glu His Pro Leu Arg Cys Leu Val Leu Cys Ala Gln Val His

-15 -10 -5

gcc gga atg tgg aga aga aat ggg ttc tct cta gta aac cag att tat 154

Ala Gly Met Trp Arg Arg Asn Gly Phe Ser Leu Val Asn Gln Ile Tyr

-1 1 5 10 15

tac tac cat aat gtg aaa tgc aga cgt gag atg ttt gac aag gat gta 202

Tyr Tyr His Asn Val Lys Cys Arg Arg Glu Met Phe Asp Lys Asp Val

20 25 30

gta atg ctt cag aca ggt gtc tcc atg atg gat cca aat cat ttc ctg 250

Val Met Leu Gln Thr Gly Val Ser Met Met Asp Pro Asn His Phe Leu

35 40 45

atg atc atg ctc agc cgc ttt gaa ctt tat cag att ttc agt act cca 298

Met Ile Met Leu Ser Arg Phe Glu Leu Tyr Gln Ile Phe Ser Thr Pro

50 55 60

gac tat gga aaa aga ttt agt tct gag att acc cat aag gat gtt gtt 346

Asp Tyr Gly Lys Arg Phe Ser Ser Glu Ile Thr His Lys Asp Val Val

65 70 75

cag cag aac aat act cta ata gaa gaa atg cta tac ctc att ata atg 394

Gln Gln Asn Asn Thr Leu Ile Glu Glu Met Leu Tyr Leu Ile Ile Met

80 85 90 95

ctt gtt gga gag aga ttt agt cct gga gtt gga cag gta aat gct aca 442

Leu Val Gly Glu Arg Phe Ser Pro Gly Val Gly Gln Val Asn Ala Thr

100 105 110

gat gaa atc aag cga gag att atc cat cag ttg agt atc aag cct atg 490

Asp Glu Ile Lys Arg Glu Ile Ile His Gln Leu Ser Ile Lys Pro Met

115 120 125

gct cat agt gaa ttg gta aag tct tta cct gaa gat gag aac aag gag 538

Ala His Ser Glu Leu Val Lys Ser Leu Pro Glu Asp Glu Asn Lys Glu

130 135 140

act ggc atg gag agt gta atc gaa gca gtt gcc cat ttc aag aaa cct 586

Thr Gly Met Glu Ser Val Ile Glu Ala Val Ala His Phe Lys Lys Pro

145 150 155

gga tta aca gga cga ggc atg tat gaa ctg aaa cca gaa tgt gcc aaa 634

Gly Leu Thr Gly Arg Gly Met Tyr Glu Leu Lys Pro Glu Cys Ala Lys

160 165 170 175

gag ttc aac ttg tat ttc tat cac ttt tca agg gca gaa cag tcc aag 682

Glu Phe Asn Leu Tyr Phe Tyr His Phe Ser Arg Ala Glu Gln Ser Lys

180 185 190

gca gaa gaa gcg caa cgg aaa ttg aaa aga caa aat aga gaa gat aca 730

Ala Glu Glu Ala Gln Arg Lys Leu Lys Arg Gln Asn Arg Glu Asp Thr

195 200 205

gca ctc cca cct ccg gtg ttg cct cca ttc tgc cct ctg ttt gca agc 778

Ala Leu Pro Pro Pro Val Leu Pro Pro Phe Cys Pro Leu Phe Ala Ser

210 215 220

ctg gtt aac att ttg cag tca gat gtc atg ttg tgc atc atg gga aca 826

Leu Val Asn Ile Leu Gln Ser Asp Val Met Leu Cys Ile Met Gly Thr

225 230 235

att ctg caa tgg gct gtg gaa cat aat gga tat gcc tgg tca gag tcc 874

Ile Leu Gln Trp Ala Val Glu His Asn Gly Tyr Ala Trp Ser Glu Ser

240 245 250 255

atg ctg caa agg gtg tta cat tta att ggc atg gca cta caa gaa gaa 922

Met Leu Gln Arg Val Leu His Leu Ile Gly Met Ala Leu Gln Glu Glu

260 265 270

aaa caa cat tta gag aat gtc acg gaa gag cat gta gta aca ttt acc 970

Lys Gln His Leu Glu Asn Val Thr Glu Glu His Val Val Thr Phe Thr

275 280 285

ttc act cag aag ata tca aaa cct ggt gaa gcg cca aaa aat tct cct 1018

Phe Thr Gln Lys Ile Ser Lys Pro Gly Glu Ala Pro Lys Asn Ser Pro

290 295 300

agc ata cta gct atg ctg gaa aca cta caa aat gct ccc tac cta gaa 1066

Ser Ile Leu Ala Met Leu Glu Thr Leu Gln Asn Ala Pro Tyr Leu Glu

305 310 315

gtc cac aaa gac atg att cgg tgg ata ttg aag act ttt aat gct gtt 1114

Val His Lys Asp Met Ile Arg Trp Ile Leu Lys Thr Phe Asn Ala Val

320 325 330 335

aaa aag atg agg gag agt tca cct acc agt ccc gtg gca gag aca gaa 1162

Lys Lys Met Arg Glu Ser Ser Pro Thr Ser Pro Val Ala Glu Thr Glu

340 345 350

gga acc ata atg gaa gag agt tca agg gac aaa gac aaa gct gag agg 1210

Gly Thr Ile Met Glu Glu Ser Ser Arg Asp Lys Asp Lys Ala Glu Arg

355 360 365

aag aga aaa gca gag att gcc aga ctg cgc aga gaa aag atc atg gct 1258

Lys Arg Lys Ala Glu Ile Ala Arg Leu Arg Arg Glu Lys Ile Met Ala

370 375 380

cag atg tct gaa atg cag cgg cat ttt att gat gaa aac aaa gaa ctc 1306

Gln Met Ser Glu Met Gln Arg His Phe Ile Asp Glu Asn Lys Glu Leu

385 390 395

ttt cag cag aca tta gaa ctg gat gcc tca acc tct gct gtt ctt gat 1354

Phe Gln Gln Thr Leu Glu Leu Asp Ala Ser Thr Ser Ala Val Leu Asp

400 405 410 415

cat agc cct gtg gct tca gat atg aca ctt aca gca ctg ggc ccc gca 1402

His Ser Pro Val Ala Ser Asp Met Thr Leu Thr Ala Leu Gly Pro Ala

420 425 430

caa act cag gtt cct gaa caa aga caa ttc gtt aca tgt ata ttg tgt 1450

Gln Thr Gln Val Pro Glu Gln Arg Gln Phe Val Thr Cys Ile Leu Cys

435 440 445

caa gag gag caa gaa gtt aaa gtg gaa agc agg gca atg gtc ttg gca 1498

Gln Glu Glu Gln Glu Val Lys Val Glu Ser Arg Ala Met Val Leu Ala

450 455 460

gca ttt gtt cag aga tca act gta tta tca aaa aac aga agt aaa ttt 1546

Ala Phe Val Gln Arg Ser Thr Val Leu Ser Lys Asn Arg Ser Lys Phe

465 470 475

att caa gat cca gaa aaa tat gat cca tta ttc atg cac cct gat ctg 1594

Ile Gln Asp Pro Glu Lys Tyr Asp Pro Leu Phe Met His Pro Asp Leu

480 485 490 495

tct tgt gga aca cac act agt agc tgt ggg cac att atg cat gcc cat 1642

Ser Cys Gly Thr His Thr Ser Ser Cys Gly His Ile Met His Ala His

500 505 510

tgt tgg caa agg tat ttt gat tcc gtt caa gct aaa gaa cag cga agg 1690

Cys Trp Gln Arg Tyr Phe Asp Ser Val Gln Ala Lys Glu Gln Arg Arg

515 520 525

caa cag aga tta cgc tta cat acg agc tat gat gta gaa aac gga gaa 1738

Gln Gln Arg Leu Arg Leu His Thr Ser Tyr Asp Val Glu Asn Gly Glu

530 535 540

ttc ctt tgc ccc ctt tgt gaa tgc ttg agt aat act gtt att cct ctg 1786

Phe Leu Cys Pro Leu Cys Glu Cys Leu Ser Asn Thr Val Ile Pro Leu

545 550 555

ctg ctt tct cca aga aat att ttt aac aac agg tta aat ttt tca gac 1834

Leu Leu Ser Pro Arg Asn Ile Phe Asn Asn Arg Leu Asn Phe Ser Asp

560 565 570 575

caa cca aat ctg act cag tgg att aga aca ata tct cag caa ata aaa 1882

Gln Pro Asn Leu Thr Gln Trp Ile Arg Thr Ile Ser Gln Gln Ile Lys

580 585 590

gca tta cag ttt ctt agg aaa gaa gaa agt act cct aat aat gcc tct 1930

Ala Leu Gln Phe Leu Arg Lys Glu Glu Ser Thr Pro Asn Asn Ala Ser

595 600 605

aca aag aat tca gaa aat gtg gat gaa tta cag ctc cct gaa ggg ttc 1978

Thr Lys Asn Ser Glu Asn Val Asp Glu Leu Gln Leu Pro Glu Gly Phe

610 615 620

agg cct gat ttt cgt cct aag atc cct tat tct gag agc ata aaa gaa 2026

Arg Pro Asp Phe Arg Pro Lys Ile Pro Tyr Ser Glu Ser Ile Lys Glu

625 630 635

atg cta acg aca ttt gga act gct acc tac aag gtg gga cta aag gtt 2074

Met Leu Thr Thr Phe Gly Thr Ala Thr Tyr Lys Val Gly Leu Lys Val

640 645 650 655

cat ccc aat gaa gag gat cct cgt gtt ccc ata atg tgt tgg ggt agc 2122

His Pro Asn Glu Glu Asp Pro Arg Val Pro Ile Met Cys Trp Gly Ser

660 665 670

tgc gcg tac acc atc caa agc ata gaa aga att ttg agt gat gaa gat 2170

Cys Ala Tyr Thr Ile Gln Ser Ile Glu Arg Ile Leu Ser Asp Glu Asp

675 680 685

aaa cca ttg ttt ggt cct tta cct tgc aga ctg gat gac tgt ctt agg 2218

Lys Pro Leu Phe Gly Pro Leu Pro Cys Arg Leu Asp Asp Cys Leu Arg

690 695 700

tca ttg acg aga ttt gcc gca gca cac tgg aca gtg gca tca gtt tca 2266

Ser Leu Thr Arg Phe Ala Ala Ala His Trp Thr Val Ala Ser Val Ser

705 710 715

gtg gtg caa gga cat ttt tgt aaa ctt ttt gca tca ctg gtg cct aat 2314

Val Val Gln Gly His Phe Cys Lys Leu Phe Ala Ser Leu Val Pro Asn

720 725 730 735

gac agc cat gag gaa ctt cca tgc ata tta gat att gac atg ttt cat 2362

Asp Ser His Glu Glu Leu Pro Cys Ile Leu Asp Ile Asp Met Phe His

740 745 750

tta ttg gtg ggc ttg gtg ctt gca ttt cct gcg ttg cag tgt cag gat 2410

Leu Leu Val Gly Leu Val Leu Ala Phe Pro Ala Leu Gln Cys Gln Asp

755 760 765

ttt tca ggg atc agc ctt ggc act gga gac ctt cac att ttc cat ctg 2458

Phe Ser Gly Ile Ser Leu Gly Thr Gly Asp Leu His Ile Phe His Leu

770 775 780

gtt act atg gca cac atc ata cag atc tta ctt acc tca tgt aca gaa 2506

Val Thr Met Ala His Ile Ile Gln Ile Leu Leu Thr Ser Cys Thr Glu

785 790 795

gag aat ggc atg gat caa gaa aat ccc cct tgt gaa gaa gaa tca gca 2554

Glu Asn Gly Met Asp Gln Glu Asn Pro Pro Cys Glu Glu Glu Ser Ala

800 805 810 815

gtt ctt gct ttg tat aaa aca ctt cac cag tat acg gga agt gcc ttg 2602

Val Leu Ala Leu Tyr Lys Thr Leu His Gln Tyr Thr Gly Ser Ala Leu

820 825 830

aaa gaa ata cca tcc ggc tgg cat ctg tgg agg agt gtc aga gct gga 2650

Lys Glu Ile Pro Ser Gly Trp His Leu Trp Arg Ser Val Arg Ala Gly

835 840 845

atc atg cct ttc ctg aag tgt tct gct tta ttt ttt cat tac tta aat 2698

Ile Met Pro Phe Leu Lys Cys Ser Ala Leu Phe Phe His Tyr Leu Asn

850 855 860

gga gtt cct tcc cca ccc gac att caa gtt cct gga aca agc cat ttt 2746

Gly Val Pro Ser Pro Pro Asp Ile Gln Val Pro Gly Thr Ser His Phe

865 870 875

gaa cat tta tgt agc tat ctt tcc cta cca aac aac ctc att tgc ctt 2794

Glu His Leu Cys Ser Tyr Leu Ser Leu Pro Asn Asn Leu Ile Cys Leu

880 885 890 895

ttt caa gaa aat agt gag ata atg aat tca ctg att gaa agt tgg tgc 2842

Phe Gln Glu Asn Ser Glu Ile Met Asn Ser Leu Ile Glu Ser Trp Cys

900 905 910

cgt aac agt gaa gtt aaa aga tat cta gaa ggt gaa aga gat gct ata 2890

Arg Asn Ser Glu Val Lys Arg Tyr Leu Glu Gly Glu Arg Asp Ala Ile

915 920 925

aga tat cca aga gaa tct aac aaa tta ata aac ctt cca gag gat tac 2938

Arg Tyr Pro Arg Glu Ser Asn Lys Leu Ile Asn Leu Pro Glu Asp Tyr

930 935 940

agc agc ctc att aat caa gca tcc aat ttc tcg tgc ccg aaa tca ggt 2986

Ser Ser Leu Ile Asn Gln Ala Ser Asn Phe Ser Cys Pro Lys Ser Gly

945 950 955

ggt gat aag agc aga gcc cca act ctg tgc ctt gtg tgc gga tct ctg 3034

Gly Asp Lys Ser Arg Ala Pro Thr Leu Cys Leu Val Cys Gly Ser Leu

960 965 970 975

ctg tgc tcc cag agt tac tgc tgc cag act gaa ctg gaa ggg gag gat 3082

Leu Cys Ser Gln Ser Tyr Cys Cys Gln Thr Glu Leu Glu Gly Glu Asp

980 985 990

gta gga gcc tgc aca gct cac acc tac tcc tgt ggc tct gga gtg ggc 3130

Val Gly Ala Cys Thr Ala His Thr Tyr Ser Cys Gly Ser Gly Val Gly

995 1000 1005

atc ttc ctg aga gta cgg gaa tgt cag gtg cta ttt tta gct ggc aaa 3178

Ile Phe Leu Arg Val Arg Glu Cys Gln Val Leu Phe Leu Ala Gly Lys

1010 1015 1020

acc aaa ggc tgt ttt tat tct cct cct tac ctt gat gac tat ggg gag 3226

Thr Lys Gly Cys Phe Tyr Ser Pro Pro Tyr Leu Asp Asp Tyr Gly Glu

1025 1030 1035

acc gac cag gga ctc aga cgg gga aat cct tta cat tta tgc aaa gag 3274

Thr Asp Gln Gly Leu Arg Arg Gly Asn Pro Leu His Leu Cys Lys Glu

1040 1045 1050 1055

cga ttc aag aag att cag aag ctc tgg cac caa cac agt gtc aca gag 3322

Arg Phe Lys Lys Ile Gln Lys Leu Trp His Gln His Ser Val Thr Glu

1060 1065 1070

gaa att gga cat gca cag gaa gcc aat cag aca ctg gtt ggc att gac 3370

Glu Ile Gly His Ala Gln Glu Ala Asn Gln Thr Leu Val Gly Ile Asp

1075 1080 1085

tgg caa cat tta taattattgc accaccaaaa aacacaaact tggatttttt 3422

Trp Gln His Leu

1090

taacccagtt ggctttttaa gaaagaaaga agttctgctg aatttggaaa taaattcttt 3482

atttaaactt taaaaaaaaa 3502

<210> SEQ ID NO 58

<211> LENGTH: 1726

<212> TYPE: PRT

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 58

Met Leu Ala Cys Leu Gln Ala Cys Ala Gly Ser Val Ser Gln Glu Leu

-10 -5 -1 1

Ser Glu Thr Ile Leu Thr Met Val Ala Asn Cys Ser Asn Val Met Asn

5 10 15

Lys Ala Arg Gln Pro Pro Pro Gly Val Met Pro Lys Gly Arg Pro Pro

20 25 30 35

Ser Ala Ser Ser Leu Asp Ala Ile Ser Pro Val Gln Ile Asp Pro Leu

40 45 50

Ala Gly Met Thr Ser Leu Ser Ile Gly Gly Ser Ala Ala Pro His Thr

55 60 65

Gln Ser Met Gln Gly Phe Pro Pro Asn Leu Gly Ser Ala Phe Ser Thr

70 75 80

Pro Gln Ser Pro Ala Lys Ala Phe Pro Pro Leu Ser Thr Pro Asn Gln

85 90 95

Thr Thr Ala Phe Ser Gly Ile Gly Gly Leu Ser Ser Gln Leu Pro Val

100 105 110 115

Gly Gly Leu Gly Thr Gly Ser Leu Thr Gly Ile Gly Thr Gly Ala Leu

120 125 130

Gly Leu Pro Ala Val Asn Asn Asp Pro Phe Val Gln Arg Lys Leu Gly

135 140 145

Thr Ser Gly Leu Asn Gln Pro Thr Phe Gln Gln Ser Lys Met Lys Pro

150 155 160

Ser Asp Leu Ser Gln Val Trp Pro Glu Ala Asn Gln His Phe Ser Lys

165 170 175

Glu Ile Asp Asp Glu Ala Asn Ser Tyr Phe Gln Arg Ile Tyr Asn His

180 185 190 195

Pro Pro His Pro Thr Met Ser Val Asp Glu Val Leu Glu Met Leu Gln

200 205 210

Arg Phe Lys Asp Ser Thr Ile Lys Arg Glu Arg Glu Val Phe Asn Cys

215 220 225

Met Leu Arg Asn Leu Phe Glu Glu Tyr Arg Phe Phe Pro Gln Tyr Pro

230 235 240

Asp Lys Glu Leu His Ile Thr Ala Cys Leu Phe Gly Gly Ile Ile Glu

245 250 255

Lys Gly Leu Val Thr Tyr Met Ala Leu Gly Leu Ala Leu Arg Tyr Val

260 265 270 275

Leu Glu Ala Leu Arg Lys Pro Phe Gly Ser Lys Met Tyr Tyr Phe Gly

280 285 290

Ile Ala Ala Leu Asp Arg Phe Lys Asn Arg Leu Lys Asp Tyr Pro Gln

295 300 305

Tyr Cys Gln His Leu Ala Ser Ile Ser His Phe Met Gln Phe Pro His

310 315 320

His Leu Gln Glu Tyr Ile Glu Tyr Gly Gln Gln Ser Arg Asp Pro Pro

325 330 335

Val Lys Met Gln Gly Ser Ile Thr Thr Pro Gly Ser Ile Ala Leu Ala

340 345 350 355

Gln Ala Gln Ala Gln Ala Gln Val Pro Ala Lys Ala Pro Leu Ala Gly

360 365 370

Gln Val Ser Thr Met Val Thr Thr Ser Thr Thr Thr Thr Val Ala Lys

375 380 385

Thr Val Thr Val Thr Arg Pro Thr Gly Val Ser Phe Lys Lys Asp Val

390 395 400

Pro Pro Ser Ile Asn Thr Thr Asn Ile Asp Thr Leu Leu Val Ala Thr

405 410 415

Asp Gln Thr Glu Arg Ile Val Glu Pro Pro Glu Asn Ile Gln Glu Lys

420 425 430 435

Ile Ala Phe Ile Phe Asn Asn Leu Ser Gln Ser Asn Met Thr Gln Lys

440 445 450

Val Glu Glu Leu Lys Glu Thr Val Lys Glu Glu Phe Met Pro Trp Val

455 460 465

Ser Gln Tyr Leu Val Met Lys Arg Val Ser Ile Glu Pro Asn Phe His

470 475 480

Ser Leu Tyr Ser Asn Phe Leu Asp Thr Leu Lys Asn Pro Glu Phe Asn

485 490 495

Lys Met Val Leu Asn Glu Thr Tyr Arg Asn Ile Lys Val Leu Leu Thr

500 505 510 515

Ser Asp Lys Ala Ala Ala Asn Phe Ser Asp Arg Ser Leu Leu Lys Asn

520 525 530

Leu Gly His Trp Leu Gly Met Ile Thr Leu Ala Lys Asn Lys Pro Ile

535 540 545

Leu His Thr Asp Leu Asp Val Lys Ser Leu Leu Leu Glu Ala Tyr Val

550 555 560

Lys Gly Gln Gln Glu Leu Leu Tyr Val Val Pro Phe Val Ala Lys Val

565 570 575

Leu Glu Ser Ser Ile Arg Ser Val Val Phe Arg Pro Pro Asn Pro Trp

580 585 590 595

Thr Met Ala Ile Met Asn Val Leu Ala Glu Leu His Gln Glu His Asp

600 605 610

Leu Lys Leu Asn Leu Lys Phe Glu Ile Glu Val Leu Cys Lys Asn Leu

615 620 625

Ala Leu Asp Ile Asn Glu Leu Lys Pro Gly Asn Leu Leu Lys Asp Lys

630 635 640

Asp Arg Leu Lys Asn Leu Asp Glu Gln Leu Ser Ala Pro Lys Lys Asp

645 650 655

Val Lys Gln Pro Glu Glu Leu Pro Pro Ile Thr Thr Thr Thr Thr Ser

660 665 670 675

Thr Thr Pro Ala Thr Asn Thr Thr Cys Thr Ala Thr Val Pro Pro Gln

680 685 690

Pro Gln Tyr Ser Tyr His Asp Ile Asn Val Tyr Ser Leu Ala Gly Leu

695 700 705

Ala Pro His Ile Thr Leu Asn Pro Thr Ile Pro Leu Phe Gln Ala His

710 715 720

Pro Gln Leu Lys Gln Cys Val Arg Gln Ala Ile Glu Arg Ala Val Gln

725 730 735

Glu Leu Val His Pro Val Val Asp Arg Ser Ile Lys Ile Ala Met Thr

740 745 750 755

Thr Cys Glu Gln Ile Val Arg Lys Asp Phe Ala Leu Asp Ser Glu Glu

760 765 770

Ser Arg Met Arg Ile Ala Ala His His Met Met Arg Asn Leu Thr Ala

775 780 785

Gly Met Ala Met Ile Thr Cys Arg Glu Pro Leu Leu Met Ser Ile Ser

790 795 800

Thr Asn Leu Lys Asn Ser Phe Ala Ser Ala Leu Arg Thr Ala Ser Pro

805 810 815

Gln Gln Arg Glu Met Met Asp Gln Ala Ala Ala Gln Leu Ala Gln Asp

820 825 830 835

Asn Cys Glu Leu Ala Cys Cys Phe Ile Gln Lys Thr Ala Val Glu Lys

840 845 850

Ala Gly Pro Glu Met Asp Lys Arg Leu Ala Thr Glu Phe Glu Leu Arg

855 860 865

Lys His Ala Arg Gln Glu Gly Arg Arg Tyr Cys Asp Pro Val Val Leu

870 875 880

Thr Tyr Gln Ala Glu Arg Met Pro Glu Gln Ile Arg Leu Lys Val Gly

885 890 895

Gly Val Asp Pro Lys Gln Leu Ala Val Tyr Glu Glu Phe Ala Arg Asn

900 905 910 915

Val Pro Gly Phe Leu Pro Thr Asn Asp Leu Ser Gln Pro Thr Gly Phe

920 925 930

Leu Ala Gln Pro Met Lys Gln Ala Trp Ala Thr Asp Asp Val Ala Gln

935 940 945

Ile Tyr Asp Lys Cys Ile Thr Glu Leu Glu Gln His Leu His Ala Ile

950 955 960

Pro Pro Thr Leu Ala Met Asn Pro Gln Ala Gln Ala Leu Arg Ser Leu

965 970 975

Leu Glu Val Val Val Leu Ser Arg Asn Ser Arg Asp Ala Ile Ala Ala

980 985 990 995

Leu Gly Leu Leu Gln Lys Ala Val Glu Gly Leu Leu Asp Ala Thr Ser

1000 1005 1010

Gly Ala Asp Ala Asp Leu Leu Leu Arg Tyr Arg Glu Cys His Leu Leu

1015 1020 1025

Val Leu Lys Ala Leu Gln Asp Gly Arg Ala Tyr Gly Ser Pro Trp Cys

1030 1035 1040

Asn Lys Gln Ile Thr Arg Cys Leu Ile Glu Cys Arg Asp Glu Tyr Lys

1045 1050 1055

Tyr Asn Val Glu Ala Val Glu Leu Leu Ile Arg Asn His Leu Val Asn

1060 1065 1070 1075

Met Gln Gln Tyr Asp Phe His Leu Ala Gln Ser Met Glu Asn Gly Leu

1080 1085 1090

Asn Tyr Met Ala Val Ala Phe Ala Met Gln Leu Val Lys Ile Leu Leu

1095 1100 1105

Val Asp Glu Arg Ser Val Ala His Val Thr Glu Ala Asp Leu Phe His

1110 1115 1120

Thr Ile Glu Thr Leu Met Arg Ile Asn Ala His Ser Arg Gly Asn Ala

1125 1130 1135

Pro Glu Gly Leu Ser Gln Leu Met Glu Val Val Arg Ser Asn Tyr Glu

1140 1145 1150 1155

Ala Met Ile Asp Arg Ala His Gly Gly Pro Asn Phe Met Met His Ser

1160 1165 1170

Gly Ile Ser Gln Ala Ser Glu Tyr Asp Asp Pro Pro Gly Leu Arg Glu

1175 1180 1185

Lys Ala Glu Tyr Leu Leu Arg Glu Trp Val Asn Leu Tyr His Ser Ala

1190 1195 1200

Ala Ala Gly Arg Asp Ser Thr Lys Ala Phe Ser Ala Phe Val Gly Gln

1205 1210 1215

Met His Gln Gln Gly Ile Leu Lys Thr Asp Asp Leu Ile Thr Arg Phe

1220 1225 1230 1235

Phe Arg Leu Cys Thr Glu Met Cys Val Glu Ile Ser Tyr Arg Ala Gln

1240 1245 1250

Ala Glu Gln Gln His Asn Pro Ala Ala Asn Pro Thr Met Ile Arg Ala

1255 1260 1265

Lys Cys Tyr His Asn Leu Asp Ala Phe Val Arg Leu Ile Ala Leu Leu

1270 1275 1280

Val Lys His Ser Gly Glu Ala Thr Asn Thr Val Thr Lys Ile Asn Leu

1285 1290 1295

Leu Asn Lys Val Leu Gly Ile Val Val Gly Val Leu Leu Gln Asp His

1300 1305 1310 1315

Asp Val Arg Gln Ser Glu Phe Gln Gln Leu Pro Tyr His Arg Ile Phe

1320 1325 1330

Ile Met Leu Leu Leu Glu Leu Asn Ala Pro Glu His Val Leu Glu Thr

1335 1340 1345

Ile Asn Phe Gln Thr Leu Thr Ala Phe Cys Asn Thr Phe His Ile Leu

1350 1355 1360

Arg Pro Thr Lys Ala Pro Gly Phe Val Tyr Ala Trp Leu Glu Leu Ile

1365 1370 1375

Ser His Arg Ile Phe Ile Ala Arg Met Leu Ala His Thr Pro Gln Gln

1380 1385 1390 1395

Lys Gly Trp Pro Met Tyr Ala Gln Leu Leu Ile Asp Leu Phe Lys Tyr

1400 1405 1410

Leu Ala Pro Phe Leu Arg Asn Val Glu Leu Thr Lys Pro Met Gln Ile

1415 1420 1425

Leu Tyr Lys Gly Thr Leu Arg Val Leu Leu Val Leu Leu His Asp Phe

1430 1435 1440

Pro Glu Phe Leu Cys Asp Tyr His Tyr Gly Phe Cys Asp Val Ile Pro

1445 1450 1455

Pro Asn Cys Ile Gln Leu Arg Asn Leu Ile Leu Ser Ala Phe Pro Arg

1460 1465 1470 1475

Asn Met Arg Leu Pro Asp Pro Phe Thr Pro Asn Leu Lys Val Asp Met

1480 1485 1490

Leu Ser Glu Ile Asn Ile Ala Pro Arg Ile Leu Thr Asn Phe Thr Gly

1495 1500 1505

Val Met Pro Pro Gln Phe Lys Lys Asp Leu Asp Ser Tyr Leu Lys Thr

1510 1515 1520

Arg Ser Pro Val Thr Phe Leu Ser Asp Leu Arg Ser Asn Leu Gln Val

1525 1530 1535

Ser Asn Glu Pro Gly Asn Arg Tyr Asn Leu Gln Leu Ile Asn Ala Leu

1540 1545 1550 1555

Val Leu Tyr Val Gly Thr Gln Ala Ile Ala His Ile His Asn Lys Gly

1560 1565 1570

Ser Thr Pro Ser Met Ser Thr Ile Thr His Ser Ala His Met Asp Ile

1575 1580 1585

Phe Gln Asn Leu Ala Val Asp Leu Asp Thr Glu Gly Arg Tyr Leu Phe

1590 1595 1600

Leu Asn Ala Ile Ala Asn Gln Leu Arg Tyr Pro Asn Ser His Thr His

1605 1610 1615

Tyr Phe Ser Cys Thr Met Leu Tyr Leu Phe Ala Glu Ala Asn Thr Glu

1620 1625 1630 1635

Ala Ile Gln Glu Gln Ile Thr Arg Val Leu Leu Glu Arg Leu Ile Val

1640 1645 1650

Asn Arg Pro His Pro Trp Gly Leu Leu Ile Thr Phe Ile Glu Leu Ile

1655 1660 1665

Lys Asn Pro Ala Phe Lys Phe Trp Asn His Glu Phe Val His Cys Ala

1670 1675 1680

Pro Glu Ile Glu Lys Leu Phe Gln Ser Val Ala Gln Cys Cys Met Gly

1685 1690 1695

Gln Lys Gln Ala Gln Gln Val Met Glu Gly Thr Gly Ala Ser

1700 1705 1710

<210> SEQ ID NO 59

<211> LENGTH: 5178

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 59

atgttggcct gtctgcaagc ttgtgcaggg agtgtttctc aggagctatc agaaactatc 60

ctcaccatgg tagccaattg cagtaatgtt atgaataagg ccagacaacc accacctgga 120

gttatgccaa aaggacgtcc tcctagtgct agcagcttag atgccatttc tcctgttcag 180

attgaccctc ttgctggaat gacatctctt agtataggtg gttcagctgc ccctcacacc 240

cagagtatgc agggttttcc tccaaatttg ggttctgcat tcagtacccc tcagtcacca 300

gcaaaagcat ttccacccct ttcaaccccc aatcagacca ctgcattcag tggtattgga 360

ggactttcat cacagcttcc agtaggtggt cttggcacag gcagcctgac tggtatagga 420

actggtgctc ttggactccc tgcagtgaat aacgaccctt ttgtacagag gaaactgggc 480

acctctggac tgaatcagcc tacattccag cagagtaaga tgaaaccttc ggacttgtct 540

caggtgtggc cagaggcaaa ccagcacttt agtaaagaga tagatgatga agcaaacagc 600

tatttccagc gaatatataa tcatccacca catccaacca tgtctgttga tgaggtatta 660

gaaatgctgc agagatttaa agactctact ataaagaggg aacgagaagt atttaactgt 720

atgctaagga acttgtttga agaatatcgt ttttttcccc agtatcctga taaagagtta 780

catataacag cctgcctatt tggtggtata attgagaaag gactggtcac ttacatggca 840

ctaggtctgg ctctacgata tgttcttgaa gccttacgca agccttttgg atccaaaatg 900

tattatttcg ggattgctgc actagataga tttaaaaaca gattgaagga ctatccccag 960

tattgtcaac atttggcttc tatcagtcac tttatgcaat ttccacatca tttacaggag 1020

tatattgagt atggacagca gtctagagat cctcctgtga aaatgcaagg ctctatcaca 1080

acccctggaa gtattgcact ggctcaggcc caggctcagg cccaggttcc agcaaaagct 1140

cctcttgctg gtcaagttag cactatggta accacctcaa caactaccac tgttgctaaa 1200

acggttacgg tcaccaggcc aactggagtc agctttaaga aagatgtgcc accttctatt 1260

aatactacaa atatagatac gttgcttgtg gccacagatc aaactgagag aattgtggag 1320

cccccagaaa atatccagga gaaaattgct tttattttca ataatctctc acagtcaaat 1380

atgacacaaa aggttgaaga gctaaaggaa acggtgaaag aagaatttat gccttgggtt 1440

tcacagtatc tggttatgaa gagagtcagt attgagccaa actttcatag cctgtattca 1500

aacttccttg acacgctgaa gaatcctgaa tttaacaaga tggttctgaa tgagacctac 1560

agaaacatta aagtgctcct gacctctgat aaagctgcag ccaatttctc agatcgttct 1620

ttgctgaaga acttgggaca ttggctagga atgatcacat tagctaaaaa caaacccatc 1680

ttacacactg acttggatgt gaaatcattg ctgctagagg cttatgttaa aggacaacaa 1740

gaattgctct atgtagtgcc ctttgttgcc aaagtcttag aatctagcat tcgtagtgtg 1800

gtttttaggc caccaaaccc ttggacaatg gcaattatga atgtattagc tgagctacat 1860

caggagcatg acttaaagtt aaacttgaag tttgaaatcg aggttctctg caagaacctt 1920

gcattagaca tcaatgagct aaaacctgga aacctcctaa aggataaaga tcgcctgaag 1980

aatttagatg agcaactctc tgctccaaag aaagatgtca agcagccaga agaactccct 2040

cccatcacaa ccacaacaac ttctactaca ccagctacca acaccacttg tacagccacg 2100

gttccaccac agccacagta cagctaccac gacatcaatg tctattccct tgcgggcttg 2160

gcaccacaca ttactctgaa tccaacaatt cccttgtttc aggcccatcc acagttgaag 2220

cagtgtgtgc gtcaggcaat tgaacgggct gtccaggagc tggtccatcc tgtggtggat 2280

cgatcaatta agattgccat gactacttgt gagcaaatag tcaggaagga ttttgccctg 2340

gattcggagg aatctcgaat gcgaatagca gctcatcaca tgatgcgtaa cttgacagct 2400

ggaatggcta tgattacatg cagggaacct ttgctcatga gcatatctac caacttaaaa 2460

aacagttttg cctcagccct tcgtactgct tccccacaac aaagagaaat gatggatcag 2520

gcagctgctc aattagctca ggacaattgt gagttggctt gctgttttat tcagaagact 2580

gcagtagaaa aagcaggccc tgagatggac aagagattag caactgaatt tgagctgaga 2640

aaacatgcta ggcaagaagg acgcagatac tgtgatcctg ttgttttaac atatcaagct 2700

gaacggatgc cagagcaaat caggctgaaa gttggtggtg tggacccaaa gcagttggct 2760

gtttatgaag agtttgcacg caatgttcct ggcttcttac ctacaaatga cttaagtcag 2820

cccacgggat ttttagccca gcccatgaag caagcttggg caacagatga tgtagctcag 2880

atttatgata agtgtattac agaactggag caacatctac atgccatccc accaactttg 2940

gccatgaacc ctcaagctca ggctcttcga agtctcttgg aggttgtagt tttatctcga 3000

aactctcggg atgccatagc tgctcttgga ttgctccaaa aggctgtaga gggcttacta 3060

gatgccacaa gtggtgctga tgctgacctt ctgctgcgct acagggaatg ccacctcttg 3120

gtcctaaaag ctctgcagga tggccgggca tatgggtctc catggtgcaa caaacagatc 3180

acaaggtgcc taattgaatg tcgagatgaa tataaatata atgtggaggc tgtggagctg 3240

ctaattcgca atcatttggt taatatgcag cagtatgatt ttcacctagc gcagtcaatg 3300

gagaatggct taaactacat ggctgtggca tttgctatgc agttagtaaa aatcctgctg 3360

gtggatgaaa ggagtgttgc tcatgttact gaggcagatc tgttccacac cattgaaacc 3420

ctcatgagga ttaatgctca ttccagaggc aatgctccag aaggattgtc ccagctgatg 3480

gaagtagtgc gatccaacta tgaagcaatg attgatcgtg ctcatggagg cccaaacttt 3540

atgatgcatt ctgggatctc tcaagcctca gagtatgatg accctccagg cctgagggag 3600

aaggcagagt atcttctgag ggaatgggtg aatctctacc attcagcagc agctggccgc 3660

gacagtacca aagctttctc tgcatttgtt ggacagatgc accagcaagg aatactgaag 3720

accgatgatc tcataacaag gttctttcgt ctgtgtactg aaatgtgtgt tgaaatcagt 3780

taccgtgctc aggctgagca gcagcacaat cctgctgcca atcccaccat gatccgagcc 3840

aagtgctatc acaacctgga tgcctttgtt cgactcattg cactgctcgt gaaacactca 3900

ggggaggcca ccaacactgt cacaaagatt aatctgctga acaaggtcct tggtatagta 3960

gtgggagttc tccttcagga tcatgatgtt cgtcagagtg aatttcagca acttccctac 4020

catcgaattt ttatcatgct tctcttggaa ctcaatgcac ctgagcatgt gttggaaacc 4080

attaatttcc agacacttac agctttctgc aatacattcc acatcttgag gcctaccaaa 4140

gctcctggct ttgtatatgc ctggcttgaa ctgatttccc atcggatatt tattgcaaga 4200

atgctggcac atacgccaca gcagaagggg tggcctatgt atgcacagct actgattgat 4260

ttattcaaat atttagcgcc tttccttaga aatgtggaac tcaccaaacc tatgcaaatc 4320

ctctacaagg gcactttaag agtgctgctg gttcttttgc atgatttccc agagttcctt 4380

tgtgattacc attatgggtt ctgtgatgtg atcccaccta attgtatcca gttaagaaat 4440

ttgatcctga gtgcctttcc aagaaacatg aggctccccg acccattcac tcctaatcta 4500

aaggtggaca tgttgagtga aattaacatt gctccccgga ttctcaccaa tttcactgga 4560

gtaatgccac ctcagttcaa aaaggatttg gattcctatc ttaaaactcg atcaccagtc 4620

actttcctgt ctgatctgcg cagcaaccta caggtatcca atgaacctgg gaatcgctac 4680

aacctccagc tcatcaatgc actggtgctc tatgtcggga ctcaggccat tgcgcacatc 4740

cacaacaagg gcagcacacc ttcaatgagc accatcactc actcagcaca catggatatc 4800

ttccagaatt tggctgtgga cttggacact gagggtcgct atctcttttt gaatgcaatt 4860

gcaaatcagc tccggtaccc aaatagccac actcactact tcagttgcac catgctgtac 4920

ctttttgcag aggccaatac ggaagccatc caagaacaga tcacaagagt tctcttggaa 4980

cggttgattg taaataggcc acatccttgg ggtcttctta ttaccttcat tgagctgatt 5040

aaaaacccag cgtttaagtt ctggaaccat gaatttgtac actgtgcccc agaaatcgaa 5100

aagttattcc agtcggtcgc acagtgctgc atgggacaga agcaggccca gcaagtaatg 5160

gaagggacag gtgccagt 5178

<210> SEQ ID NO 60

<211> LENGTH: 5457

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<220> FEATURE:

<221> NAME/KEY: sig_peptide

<222> LOCATION: (8)..(46)

<221> NAME/KEY: mat_peptide

<222> LOCATION: (47)..(5185)

<221> NAME/KEY: CDS

<222> LOCATION: (8)..(5185)

<400> SEQUENCE: 60

ggcgaca atg ttg gcc tgt ctg caa gct tgt gca ggg agt gtt tct cag 49

Met Leu Ala Cys Leu Gln Ala Cys Ala Gly Ser Val Ser Gln

-10 -5 -1 1

gag cta tca gaa act atc ctc acc atg gta gcc aat tgc agt aat gtt 97

Glu Leu Ser Glu Thr Ile Leu Thr Met Val Ala Asn Cys Ser Asn Val

5 10 15

atg aat aag gcc aga caa cca cca cct gga gtt atg cca aaa gga cgt 145

Met Asn Lys Ala Arg Gln Pro Pro Pro Gly Val Met Pro Lys Gly Arg

20 25 30

cct cct agt gct agc agc tta gat gcc att tct cct gtt cag att gac 193

Pro Pro Ser Ala Ser Ser Leu Asp Ala Ile Ser Pro Val Gln Ile Asp

35 40 45

cct ctt gct gga atg aca tct ctt agt ata ggt ggt tca gct gcc cct 241

Pro Leu Ala Gly Met Thr Ser Leu Ser Ile Gly Gly Ser Ala Ala Pro

50 55 60 65

cac acc cag agt atg cag ggt ttt cct cca aat ttg ggt tct gca ttc 289

His Thr Gln Ser Met Gln Gly Phe Pro Pro Asn Leu Gly Ser Ala Phe

70 75 80

agt acc cct cag tca cca gca aaa gca ttt cca ccc ctt tca acc ccc 337

Ser Thr Pro Gln Ser Pro Ala Lys Ala Phe Pro Pro Leu Ser Thr Pro

85 90 95

aat cag acc act gca ttc agt ggt att gga gga ctt tca tca cag ctt 385

Asn Gln Thr Thr Ala Phe Ser Gly Ile Gly Gly Leu Ser Ser Gln Leu

100 105 110

cca gta ggt ggt ctt ggc aca ggc agc ctg act ggt ata gga act ggt 433

Pro Val Gly Gly Leu Gly Thr Gly Ser Leu Thr Gly Ile Gly Thr Gly

115 120 125

gct ctt gga ctc cct gca gtg aat aac gac cct ttt gta cag agg aaa 481

Ala Leu Gly Leu Pro Ala Val Asn Asn Asp Pro Phe Val Gln Arg Lys

130 135 140 145

ctg ggc acc tct gga ctg aat cag cct aca ttc cag cag agt aag atg 529

Leu Gly Thr Ser Gly Leu Asn Gln Pro Thr Phe Gln Gln Ser Lys Met

150 155 160

aaa cct tcg gac ttg tct cag gtg tgg cca gag gca aac cag cac ttt 577

Lys Pro Ser Asp Leu Ser Gln Val Trp Pro Glu Ala Asn Gln His Phe

165 170 175

agt aaa gag ata gat gat gaa gca aac agc tat ttc cag cga ata tat 625

Ser Lys Glu Ile Asp Asp Glu Ala Asn Ser Tyr Phe Gln Arg Ile Tyr

180 185 190

aat cat cca cca cat cca acc atg tct gtt gat gag gta tta gaa atg 673

Asn His Pro Pro His Pro Thr Met Ser Val Asp Glu Val Leu Glu Met

195 200 205

ctg cag aga ttt aaa gac tct act ata aag agg gaa cga gaa gta ttt 721

Leu Gln Arg Phe Lys Asp Ser Thr Ile Lys Arg Glu Arg Glu Val Phe

210 215 220 225

aac tgt atg cta agg aac ttg ttt gaa gaa tat cgt ttt ttt ccc cag 769

Asn Cys Met Leu Arg Asn Leu Phe Glu Glu Tyr Arg Phe Phe Pro Gln

230 235 240

tat cct gat aaa gag tta cat ata aca gcc tgc cta ttt ggt ggt ata 817

Tyr Pro Asp Lys Glu Leu His Ile Thr Ala Cys Leu Phe Gly Gly Ile

245 250 255

att gag aaa gga ctg gtc act tac atg gca cta ggt ctg gct cta cga 865

Ile Glu Lys Gly Leu Val Thr Tyr Met Ala Leu Gly Leu Ala Leu Arg

260 265 270

tat gtt ctt gaa gcc tta cgc aag cct ttt gga tcc aaa atg tat tat 913

Tyr Val Leu Glu Ala Leu Arg Lys Pro Phe Gly Ser Lys Met Tyr Tyr

275 280 285

ttc ggg att gct gca cta gat aga ttt aaa aac aga ttg aag gac tat 961

Phe Gly Ile Ala Ala Leu Asp Arg Phe Lys Asn Arg Leu Lys Asp Tyr

290 295 300 305

ccc cag tat tgt caa cat ttg gct tct atc agt cac ttt atg caa ttt 1009

Pro Gln Tyr Cys Gln His Leu Ala Ser Ile Ser His Phe Met Gln Phe

310 315 320

cca cat cat tta cag gag tat att gag tat gga cag cag tct aga gat 1057

Pro His His Leu Gln Glu Tyr Ile Glu Tyr Gly Gln Gln Ser Arg Asp

325 330 335

cct cct gtg aaa atg caa ggc tct atc aca acc cct gga agt att gca 1105

Pro Pro Val Lys Met Gln Gly Ser Ile Thr Thr Pro Gly Ser Ile Ala

340 345 350

ctg gct cag gcc cag gct cag gcc cag gtt cca gca aaa gct cct ctt 1153

Leu Ala Gln Ala Gln Ala Gln Ala Gln Val Pro Ala Lys Ala Pro Leu

355 360 365

gct ggt caa gtt agc act atg gta acc acc tca aca act acc act gtt 1201

Ala Gly Gln Val Ser Thr Met Val Thr Thr Ser Thr Thr Thr Thr Val

370 375 380 385

gct aaa acg gtt acg gtc acc agg cca act gga gtc agc ttt aag aaa 1249

Ala Lys Thr Val Thr Val Thr Arg Pro Thr Gly Val Ser Phe Lys Lys

390 395 400

gat gtg cca cct tct att aat act aca aat ata gat acg ttg ctt gtg 1297

Asp Val Pro Pro Ser Ile Asn Thr Thr Asn Ile Asp Thr Leu Leu Val

405 410 415

gcc aca gat caa act gag aga att gtg gag ccc cca gaa aat atc cag 1345

Ala Thr Asp Gln Thr Glu Arg Ile Val Glu Pro Pro Glu Asn Ile Gln

420 425 430

gag aaa att gct ttt att ttc aat aat ctc tca cag tca aat atg aca 1393

Glu Lys Ile Ala Phe Ile Phe Asn Asn Leu Ser Gln Ser Asn Met Thr

435 440 445

caa aag gtt gaa gag cta aag gaa acg gtg aaa gaa gaa ttt atg cct 1441

Gln Lys Val Glu Glu Leu Lys Glu Thr Val Lys Glu Glu Phe Met Pro

450 455 460 465

tgg gtt tca cag tat ctg gtt atg aag aga gtc agt att gag cca aac 1489

Trp Val Ser Gln Tyr Leu Val Met Lys Arg Val Ser Ile Glu Pro Asn

470 475 480

ttt cat agc ctg tat tca aac ttc ctt gac acg ctg aag aat cct gaa 1537

Phe His Ser Leu Tyr Ser Asn Phe Leu Asp Thr Leu Lys Asn Pro Glu

485 490 495

ttt aac aag atg gtt ctg aat gag acc tac aga aac att aaa gtg ctc 1585

Phe Asn Lys Met Val Leu Asn Glu Thr Tyr Arg Asn Ile Lys Val Leu

500 505 510

ctg acc tct gat aaa gct gca gcc aat ttc tca gat cgt tct ttg ctg 1633

Leu Thr Ser Asp Lys Ala Ala Ala Asn Phe Ser Asp Arg Ser Leu Leu

515 520 525

aag aac ttg gga cat tgg cta gga atg atc aca tta gct aaa aac aaa 1681

Lys Asn Leu Gly His Trp Leu Gly Met Ile Thr Leu Ala Lys Asn Lys

530 535 540 545

ccc atc tta cac act gac ttg gat gtg aaa tca ttg ctg cta gag gct 1729

Pro Ile Leu His Thr Asp Leu Asp Val Lys Ser Leu Leu Leu Glu Ala

550 555 560

tat gtt aaa gga caa caa gaa ttg ctc tat gta gtg ccc ttt gtt gcc 1777

Tyr Val Lys Gly Gln Gln Glu Leu Leu Tyr Val Val Pro Phe Val Ala

565 570 575

aaa gtc tta gaa tct agc att cgt agt gtg gtt ttt agg cca cca aac 1825

Lys Val Leu Glu Ser Ser Ile Arg Ser Val Val Phe Arg Pro Pro Asn

580 585 590

cct tgg aca atg gca att atg aat gta tta gct gag cta cat cag gag 1873

Pro Trp Thr Met Ala Ile Met Asn Val Leu Ala Glu Leu His Gln Glu

595 600 605

cat gac tta aag tta aac ttg aag ttt gaa atc gag gtt ctc tgc aag 1921

His Asp Leu Lys Leu Asn Leu Lys Phe Glu Ile Glu Val Leu Cys Lys

610 615 620 625

aac ctt gca tta gac atc aat gag cta aaa cct gga aac ctc cta aag 1969

Asn Leu Ala Leu Asp Ile Asn Glu Leu Lys Pro Gly Asn Leu Leu Lys

630 635 640

gat aaa gat cgc ctg aag aat tta gat gag caa ctc tct gct cca aag 2017

Asp Lys Asp Arg Leu Lys Asn Leu Asp Glu Gln Leu Ser Ala Pro Lys

645 650 655

aaa gat gtc aag cag cca gaa gaa ctc cct ccc atc aca acc aca aca 2065

Lys Asp Val Lys Gln Pro Glu Glu Leu Pro Pro Ile Thr Thr Thr Thr

660 665 670

act tct act aca cca gct acc aac acc act tgt aca gcc acg gtt cca 2113

Thr Ser Thr Thr Pro Ala Thr Asn Thr Thr Cys Thr Ala Thr Val Pro

675 680 685

cca cag cca cag tac agc tac cac gac atc aat gtc tat tcc ctt gcg 2161

Pro Gln Pro Gln Tyr Ser Tyr His Asp Ile Asn Val Tyr Ser Leu Ala

690 695 700 705

ggc ttg gca cca cac att act ctg aat cca aca att ccc ttg ttt cag 2209

Gly Leu Ala Pro His Ile Thr Leu Asn Pro Thr Ile Pro Leu Phe Gln

710 715 720

gcc cat cca cag ttg aag cag tgt gtg cgt cag gca att gaa cgg gct 2257

Ala His Pro Gln Leu Lys Gln Cys Val Arg Gln Ala Ile Glu Arg Ala

725 730 735

gtc cag gag ctg gtc cat cct gtg gtg gat cga tca att aag att gcc 2305

Val Gln Glu Leu Val His Pro Val Val Asp Arg Ser Ile Lys Ile Ala

740 745 750

atg act act tgt gag caa ata gtc agg aag gat ttt gcc ctg gat tcg 2353

Met Thr Thr Cys Glu Gln Ile Val Arg Lys Asp Phe Ala Leu Asp Ser

755 760 765

gag gaa tct cga atg cga ata gca gct cat cac atg atg cgt aac ttg 2401

Glu Glu Ser Arg Met Arg Ile Ala Ala His His Met Met Arg Asn Leu

770 775 780 785

aca gct gga atg gct atg att aca tgc agg gaa cct ttg ctc atg agc 2449

Thr Ala Gly Met Ala Met Ile Thr Cys Arg Glu Pro Leu Leu Met Ser

790 795 800

ata tct acc aac tta aaa aac agt ttt gcc tca gcc ctt cgt act gct 2497

Ile Ser Thr Asn Leu Lys Asn Ser Phe Ala Ser Ala Leu Arg Thr Ala

805 810 815

tcc cca caa caa aga gaa atg atg gat cag gca gct gct caa tta gct 2545

Ser Pro Gln Gln Arg Glu Met Met Asp Gln Ala Ala Ala Gln Leu Ala

820 825 830

cag gac aat tgt gag ttg gct tgc tgt ttt att cag aag act gca gta 2593

Gln Asp Asn Cys Glu Leu Ala Cys Cys Phe Ile Gln Lys Thr Ala Val

835 840 845

gaa aaa gca ggc cct gag atg gac aag aga tta gca act gaa ttt gag 2641

Glu Lys Ala Gly Pro Glu Met Asp Lys Arg Leu Ala Thr Glu Phe Glu

850 855 860 865

ctg aga aaa cat gct agg caa gaa gga cgc aga tac tgt gat cct gtt 2689

Leu Arg Lys His Ala Arg Gln Glu Gly Arg Arg Tyr Cys Asp Pro Val

870 875 880

gtt tta aca tat caa gct gaa cgg atg cca gag caa atc agg ctg aaa 2737

Val Leu Thr Tyr Gln Ala Glu Arg Met Pro Glu Gln Ile Arg Leu Lys

885 890 895

gtt ggt ggt gtg gac cca aag cag ttg gct gtt tat gaa gag ttt gca 2785

Val Gly Gly Val Asp Pro Lys Gln Leu Ala Val Tyr Glu Glu Phe Ala

900 905 910

cgc aat gtt cct ggc ttc tta cct aca aat gac tta agt cag ccc acg 2833

Arg Asn Val Pro Gly Phe Leu Pro Thr Asn Asp Leu Ser Gln Pro Thr

915 920 925

gga ttt tta gcc cag ccc atg aag caa gct tgg gca aca gat gat gta 2881

Gly Phe Leu Ala Gln Pro Met Lys Gln Ala Trp Ala Thr Asp Asp Val

930 935 940 945

gct cag att tat gat aag tgt att aca gaa ctg gag caa cat cta cat 2929

Ala Gln Ile Tyr Asp Lys Cys Ile Thr Glu Leu Glu Gln His Leu His

950 955 960

gcc atc cca cca act ttg gcc atg aac cct caa gct cag gct ctt cga 2977

Ala Ile Pro Pro Thr Leu Ala Met Asn Pro Gln Ala Gln Ala Leu Arg

965 970 975

agt ctc ttg gag gtt gta gtt tta tct cga aac tct cgg gat gcc ata 3025

Ser Leu Leu Glu Val Val Val Leu Ser Arg Asn Ser Arg Asp Ala Ile

980 985 990

gct gct ctt gga ttg ctc caa aag gct gta gag ggc tta cta gat gcc 3073

Ala Ala Leu Gly Leu Leu Gln Lys Ala Val Glu Gly Leu Leu Asp Ala

995 1000 1005

aca agt ggt gct gat gct gac ctt ctg ctg cgc tac agg gaa tgc cac 3121

Thr Ser Gly Ala Asp Ala Asp Leu Leu Leu Arg Tyr Arg Glu Cys His

1010 1015 1020 1025

ctc ttg gtc cta aaa gct ctg cag gat ggc cgg gca tat ggg tct cca 3169

Leu Leu Val Leu Lys Ala Leu Gln Asp Gly Arg Ala Tyr Gly Ser Pro

1030 1035 1040

tgg tgc aac aaa cag atc aca agg tgc cta att gaa tgt cga gat gaa 3217

Trp Cys Asn Lys Gln Ile Thr Arg Cys Leu Ile Glu Cys Arg Asp Glu

1045 1050 1055

tat aaa tat aat gtg gag gct gtg gag ctg cta att cgc aat cat ttg 3265

Tyr Lys Tyr Asn Val Glu Ala Val Glu Leu Leu Ile Arg Asn His Leu

1060 1065 1070

gtt aat atg cag cag tat gat ttt cac cta gcg cag tca atg gag aat 3313

Val Asn Met Gln Gln Tyr Asp Phe His Leu Ala Gln Ser Met Glu Asn

1075 1080 1085

ggc tta aac tac atg gct gtg gca ttt gct atg cag tta gta aaa atc 3361

Gly Leu Asn Tyr Met Ala Val Ala Phe Ala Met Gln Leu Val Lys Ile

1090 1095 1100 1105

ctg ctg gtg gat gaa agg agt gtt gct cat gtt act gag gca gat ctg 3409

Leu Leu Val Asp Glu Arg Ser Val Ala His Val Thr Glu Ala Asp Leu

1110 1115 1120

ttc cac acc att gaa acc ctc atg agg att aat gct cat tcc aga ggc 3457

Phe His Thr Ile Glu Thr Leu Met Arg Ile Asn Ala His Ser Arg Gly

1125 1130 1135

aat gct cca gaa gga ttg tcc cag ctg atg gaa gta gtg cga tcc aac 3505

Asn Ala Pro Glu Gly Leu Ser Gln Leu Met Glu Val Val Arg Ser Asn

1140 1145 1150

tat gaa gca atg att gat cgt gct cat gga ggc cca aac ttt atg atg 3553

Tyr Glu Ala Met Ile Asp Arg Ala His Gly Gly Pro Asn Phe Met Met

1155 1160 1165

cat tct ggg atc tct caa gcc tca gag tat gat gac cct cca ggc ctg 3601

His Ser Gly Ile Ser Gln Ala Ser Glu Tyr Asp Asp Pro Pro Gly Leu

1170 1175 1180 1185

agg gag aag gca gag tat ctt ctg agg gaa tgg gtg aat ctc tac cat 3649

Arg Glu Lys Ala Glu Tyr Leu Leu Arg Glu Trp Val Asn Leu Tyr His

1190 1195 1200

tca gca gca gct ggc cgc gac agt acc aaa gct ttc tct gca ttt gtt 3697

Ser Ala Ala Ala Gly Arg Asp Ser Thr Lys Ala Phe Ser Ala Phe Val

1205 1210 1215

gga cag atg cac cag caa gga ata ctg aag acc gat gat ctc ata aca 3745

Gly Gln Met His Gln Gln Gly Ile Leu Lys Thr Asp Asp Leu Ile Thr

1220 1225 1230

agg ttc ttt cgt ctg tgt act gaa atg tgt gtt gaa atc agt tac cgt 3793

Arg Phe Phe Arg Leu Cys Thr Glu Met Cys Val Glu Ile Ser Tyr Arg

1235 1240 1245

gct cag gct gag cag cag cac aat cct gct gcc aat ccc acc atg atc 3841

Ala Gln Ala Glu Gln Gln His Asn Pro Ala Ala Asn Pro Thr Met Ile

1250 1255 1260 1265

cga gcc aag tgc tat cac aac ctg gat gcc ttt gtt cga ctc att gca 3889

Arg Ala Lys Cys Tyr His Asn Leu Asp Ala Phe Val Arg Leu Ile Ala

1270 1275 1280

ctg ctc gtg aaa cac tca ggg gag gcc acc aac act gtc aca aag att 3937

Leu Leu Val Lys His Ser Gly Glu Ala Thr Asn Thr Val Thr Lys Ile

1285 1290 1295

aat ctg ctg aac aag gtc ctt ggt ata gta gtg gga gtt ctc ctt cag 3985

Asn Leu Leu Asn Lys Val Leu Gly Ile Val Val Gly Val Leu Leu Gln

1300 1305 1310

gat cat gat gtt cgt cag agt gaa ttt cag caa ctt ccc tac cat cga 4033

Asp His Asp Val Arg Gln Ser Glu Phe Gln Gln Leu Pro Tyr His Arg

1315 1320 1325

att ttt atc atg ctt ctc ttg gaa ctc aat gca cct gag cat gtg ttg 4081

Ile Phe Ile Met Leu Leu Leu Glu Leu Asn Ala Pro Glu His Val Leu

1330 1335 1340 1345

gaa acc att aat ttc cag aca ctt aca gct ttc tgc aat aca ttc cac 4129

Glu Thr Ile Asn Phe Gln Thr Leu Thr Ala Phe Cys Asn Thr Phe His

1350 1355 1360

atc ttg agg cct acc aaa gct cct ggc ttt gta tat gcc tgg ctt gaa 4177

Ile Leu Arg Pro Thr Lys Ala Pro Gly Phe Val Tyr Ala Trp Leu Glu

1365 1370 1375

ctg att tcc cat cgg ata ttt att gca aga atg ctg gca cat acg cca 4225

Leu Ile Ser His Arg Ile Phe Ile Ala Arg Met Leu Ala His Thr Pro

1380 1385 1390

cag cag aag ggg tgg cct atg tat gca cag cta ctg att gat tta ttc 4273

Gln Gln Lys Gly Trp Pro Met Tyr Ala Gln Leu Leu Ile Asp Leu Phe

1395 1400 1405

aaa tat tta gcg cct ttc ctt aga aat gtg gaa ctc acc aaa cct atg 4321

Lys Tyr Leu Ala Pro Phe Leu Arg Asn Val Glu Leu Thr Lys Pro Met

1410 1415 1420 1425

caa atc ctc tac aag ggc act tta aga gtg ctg ctg gtt ctt ttg cat 4369

Gln Ile Leu Tyr Lys Gly Thr Leu Arg Val Leu Leu Val Leu Leu His

1430 1435 1440

gat ttc cca gag ttc ctt tgt gat tac cat tat ggg ttc tgt gat gtg 4417

Asp Phe Pro Glu Phe Leu Cys Asp Tyr His Tyr Gly Phe Cys Asp Val

1445 1450 1455

atc cca cct aat tgt atc cag tta aga aat ttg atc ctg agt gcc ttt 4465

Ile Pro Pro Asn Cys Ile Gln Leu Arg Asn Leu Ile Leu Ser Ala Phe

1460 1465 1470

cca aga aac atg agg ctc ccc gac cca ttc act cct aat cta aag gtg 4513

Pro Arg Asn Met Arg Leu Pro Asp Pro Phe Thr Pro Asn Leu Lys Val

1475 1480 1485

gac atg ttg agt gaa att aac att gct ccc cgg att ctc acc aat ttc 4561

Asp Met Leu Ser Glu Ile Asn Ile Ala Pro Arg Ile Leu Thr Asn Phe

1490 1495 1500 1505

act gga gta atg cca cct cag ttc aaa aag gat ttg gat tcc tat ctt 4609

Thr Gly Val Met Pro Pro Gln Phe Lys Lys Asp Leu Asp Ser Tyr Leu

1510 1515 1520

aaa act cga tca cca gtc act ttc ctg tct gat ctg cgc agc aac cta 4657

Lys Thr Arg Ser Pro Val Thr Phe Leu Ser Asp Leu Arg Ser Asn Leu

1525 1530 1535

cag gta tcc aat gaa cct ggg aat cgc tac aac ctc cag ctc atc aat 4705

Gln Val Ser Asn Glu Pro Gly Asn Arg Tyr Asn Leu Gln Leu Ile Asn

1540 1545 1550

gca ctg gtg ctc tat gtc ggg act cag gcc att gcg cac atc cac aac 4753

Ala Leu Val Leu Tyr Val Gly Thr Gln Ala Ile Ala His Ile His Asn

1555 1560 1565

aag ggc agc aca cct tca atg agc acc atc act cac tca gca cac atg 4801

Lys Gly Ser Thr Pro Ser Met Ser Thr Ile Thr His Ser Ala His Met

1570 1575 1580 1585

gat atc ttc cag aat ttg gct gtg gac ttg gac act gag ggt cgc tat 4849

Asp Ile Phe Gln Asn Leu Ala Val Asp Leu Asp Thr Glu Gly Arg Tyr

1590 1595 1600

ctc ttt ttg aat gca att gca aat cag ctc cgg tac cca aat agc cac 4897

Leu Phe Leu Asn Ala Ile Ala Asn Gln Leu Arg Tyr Pro Asn Ser His

1605 1610 1615

act cac tac ttc agt tgc acc atg ctg tac ctt ttt gca gag gcc aat 4945

Thr His Tyr Phe Ser Cys Thr Met Leu Tyr Leu Phe Ala Glu Ala Asn

1620 1625 1630

acg gaa gcc atc caa gaa cag atc aca aga gtt ctc ttg gaa cgg ttg 4993

Thr Glu Ala Ile Gln Glu Gln Ile Thr Arg Val Leu Leu Glu Arg Leu

1635 1640 1645

att gta aat agg cca cat cct tgg ggt ctt ctt att acc ttc att gag 5041

Ile Val Asn Arg Pro His Pro Trp Gly Leu Leu Ile Thr Phe Ile Glu

1650 1655 1660 1665

ctg att aaa aac cca gcg ttt aag ttc tgg aac cat gaa ttt gta cac 5089

Leu Ile Lys Asn Pro Ala Phe Lys Phe Trp Asn His Glu Phe Val His

1670 1675 1680

tgt gcc cca gaa atc gaa aag tta ttc cag tcg gtc gca cag tgc tgc 5137

Cys Ala Pro Glu Ile Glu Lys Leu Phe Gln Ser Val Ala Gln Cys Cys

1685 1690 1695

atg gga cag aag cag gcc cag caa gta atg gaa ggg aca ggt gcc agt 5185

Met Gly Gln Lys Gln Ala Gln Gln Val Met Glu Gly Thr Gly Ala Ser

1700 1705 1710

tagacgaaac tgcatctctg ttgtacgtgt cagtctagag gtctcactgc accgagttca 5245

taaactgact gaagaatcct ttcagctctt cctgactttc ccagcccttt ggtttgtggg 5305

tatctgcccc aactactgtt gggatcagcc tcctgtctta tgtgggcacg ttccaaagtt 5365

taaatgcatt tttttgactc ttggccaaaa tttagaagat gctgtgaata tcattttgaa 5425

cttgtgtaaa tacatgaaaa aaaaaaaaaa aa 5457

<210> SEQ ID NO 61

<211> LENGTH: 453

<212> TYPE: PRT

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 61

Met Lys Leu Leu Val Ile Leu Leu Phe Ser Gly Leu Ile Thr Gly Phe

-15 -10 -5 -1 1

Arg Ser Asp Ser Ser Ser Ser Leu Pro Pro Lys Leu Leu Leu Val Ser

5 10 15

Phe Asp Gly Phe Arg Ala Asp Tyr Leu Lys Asn Tyr Glu Phe Pro His

20 25 30

Leu Gln Asn Phe Ile Lys Glu Gly Val Leu Val Glu His Val Lys Asn

35 40 45

Val Phe Ile Thr Lys Thr Phe Pro Asn His Tyr Ser Ile Val Thr Gly

50 55 60 65

Leu Tyr Glu Glu Ser His Gly Ile Val Ala Asn Ser Met Tyr Asp Ala

70 75 80

Val Thr Lys Lys His Phe Ser Asp Ser Asn Asp Lys Asp Pro Phe Trp

85 90 95

Trp Asn Glu Ala Val Pro Ile Trp Val Thr Asn Gln Leu Gln Glu Asn

100 105 110

Arg Ser Ser Ala Ala Ala Met Trp Pro Gly Thr Asp Val Pro Ile His

115 120 125

Asp Thr Ile Ser Ser Tyr Phe Met Asn Tyr Asn Ser Ser Val Ser Phe

130 135 140 145

Glu Glu Arg Leu Asn Asn Ile Thr Met Trp Leu Asn Asn Ser Asn Pro

150 155 160

Pro Val Thr Phe Ala Thr Leu Tyr Trp Glu Glu Pro Asp Ala Ser Gly

165 170 175

His Lys Tyr Gly Pro Glu Asp Lys Glu Asn Met Ser Arg Val Leu Lys

180 185 190

Lys Ile Asp Asp Leu Ile Gly Asp Leu Val Gln Arg Leu Lys Met Leu

195 200 205

Gly Leu Trp Glu Asn Leu Asn Val Ile Ile Thr Ser Asp His Gly Met

210 215 220 225

Thr Gln Cys Ser Gln Asp Arg Leu Ile Asn Leu Asp Ser Cys Ile Asp

230 235 240

His Ser Tyr Tyr Thr Leu Ile Asp Leu Ser Pro Val Ala Ala Ile Leu

245 250 255

Pro Lys Ile Asn Arg Thr Glu Val Tyr Asn Lys Leu Lys Asn Cys Ser

260 265 270

Pro His Met Asn Val Tyr Leu Lys Glu Asp Ile Pro Asn Arg Phe Tyr

275 280 285

Tyr Gln His Asn Asp Arg Ile Gln Pro Ile Ile Leu Val Ala Asp Glu

290 295 300 305

Gly Trp Thr Ile Val Leu Asn Glu Ser Ser Gln Lys Leu Gly Asp His

310 315 320

Gly Tyr Asp Asn Ser Leu Pro Ser Met His Pro Phe Leu Ala Ala His

325 330 335

Gly Pro Ala Phe His Lys Gly Tyr Lys His Ser Thr Ile Asn Ile Val

340 345 350

Asp Ile Tyr Pro Met Met Cys His Ile Leu Gly Leu Lys Pro His Pro

355 360 365

Asn Asn Gly Thr Phe Gly His Thr Lys Cys Leu Leu Val Asp Gln Trp

370 375 380 385

Cys Ile Asn Leu Pro Glu Ala Ile Ala Ile Val Ile Gly Ser Leu Leu

390 395 400

Val Leu Thr Met Leu Thr Cys Leu Ile Ile Ile Met Gln Asn Arg Leu

405 410 415

Ser Val Pro Arg Pro Phe Ser Arg Leu Gln Leu Gln Glu Asp Asp Asp

420 425 430

Asp Pro Leu Ile Gly

435

<210> SEQ ID NO 62

<211> LENGTH: 1359

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 62

atgaagttat tagtaatact tttgttttct ggacttataa ctggttttag aagtgactct 60

tcctctagtt tgccacctaa gttactacta gtatcctttg atggcttcag agctgattat 120

ctgaagaact atgaatttcc tcatctccag aattttatca aagaaggtgt tttggtagag 180

catgttaaaa atgtttttat cacaaaaaca tttccaaacc actacagtat tgtgacaggc 240

ttgtatgaag aaagccatgg cattgtggct aattccatgt atgatgcagt cacaaagaaa 300

cacttttctg actctaatga caaggatcct ttttggtgga atgaggcagt acctatttgg 360

gtgaccaatc agcttcagga aaacagatca agtgctgctg ctatgtggcc tggtactgat 420

gtacccattc acgataccat ctcttcctat tttatgaatt acaactcctc agtgtcattt 480

gaggaaagac taaataatat tactatgtgg ctaaacaatt cgaacccacc agtcaccttt 540

gcaacactat attgggaaga accagatgca agtggccaca aatacggacc tgaagataaa 600

gaaaacatga gcagagtgtt gaaaaaaata gatgatctta tcggtgactt agtccaaaga 660

ctcaagatgt tagggctatg ggaaaatctt aatgtgatca ttacaagtga tcatgggatg 720

acccagtgtt ctcaggacag actgataaac ctggattcct gcatcgatca ttcatactac 780

actcttatag atttgagccc agttgctgca atacttccca aaataaatag aacagaggtt 840

tataacaaac tgaaaaactg tagccctcat atgaatgttt atctcaaaga agacattcct 900

aacagatttt attaccaaca taatgatcga attcagccca ttattttggt tgccgatgaa 960

ggctggacaa ttgtgctaaa tgaatcatca caaaaattag gtgaccatgg ttatgataat 1020

tctttgccta gtatgcatcc atttctagct gcccacggac ctgcatttca caaaggctac 1080

aagcatagca caattaacat tgtggatatt tatccaatga tgtgccacat cctgggatta 1140

aaaccacatc ccaataatgg gacctttggt catactaagt gcttgttagt tgaccagtgg 1200

tgcattaatc tcccagaagc catcgcgatt gttatcggtt cactcttggt gttaaccatg 1260

ctaacatgcc tcataataat catgcagaat agactttctg tacctcgtcc attttctcga 1320

cttcagctac aagaagatga tgatgatccc ttaattggg 1359

<210> SEQ ID NO 63

<211> LENGTH: 2044

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<220> FEATURE:

<221> NAME/KEY: sig_peptide

<222> LOCATION: (70)..(114)

<221> NAME/KEY: mat_peptide

<222> LOCATION: (115)..(1428)

<221> NAME/KEY: CDS

<222> LOCATION: (70)..(1428)

<400> SEQUENCE: 63

gttccgcgca ttggaaagaa gcgaccgcgg cggctggaac cctgattgct gtccttcaac 60

gtgttcatt atg aag tta tta gta ata ctt ttg ttt tct gga ctt ata act 111

Met Lys Leu Leu Val Ile Leu Leu Phe Ser Gly Leu Ile Thr

-15 -10 -5

ggt ttt aga agt gac tct tcc tct agt ttg cca cct aag tta cta cta 159

Gly Phe Arg Ser Asp Ser Ser Ser Ser Leu Pro Pro Lys Leu Leu Leu

-1 1 5 10 15

gta tcc ttt gat ggc ttc aga gct gat tat ctg aag aac tat gaa ttt 207

Val Ser Phe Asp Gly Phe Arg Ala Asp Tyr Leu Lys Asn Tyr Glu Phe

20 25 30

cct cat ctc cag aat ttt atc aaa gaa ggt gtt ttg gta gag cat gtt 255

Pro His Leu Gln Asn Phe Ile Lys Glu Gly Val Leu Val Glu His Val

35 40 45

aaa aat gtt ttt atc aca aaa aca ttt cca aac cac tac agt att gtg 303

Lys Asn Val Phe Ile Thr Lys Thr Phe Pro Asn His Tyr Ser Ile Val

50 55 60

aca ggc ttg tat gaa gaa agc cat ggc att gtg gct aat tcc atg tat 351

Thr Gly Leu Tyr Glu Glu Ser His Gly Ile Val Ala Asn Ser Met Tyr

65 70 75

gat gca gtc aca aag aaa cac ttt tct gac tct aat gac aag gat cct 399

Asp Ala Val Thr Lys Lys His Phe Ser Asp Ser Asn Asp Lys Asp Pro

80 85 90 95

ttt tgg tgg aat gag gca gta cct att tgg gtg acc aat cag ctt cag 447

Phe Trp Trp Asn Glu Ala Val Pro Ile Trp Val Thr Asn Gln Leu Gln

100 105 110

gaa aac aga tca agt gct gct gct atg tgg cct ggt act gat gta ccc 495

Glu Asn Arg Ser Ser Ala Ala Ala Met Trp Pro Gly Thr Asp Val Pro

115 120 125

att cac gat acc atc tct tcc tat ttt atg aat tac aac tcc tca gtg 543

Ile His Asp Thr Ile Ser Ser Tyr Phe Met Asn Tyr Asn Ser Ser Val

130 135 140

tca ttt gag gaa aga cta aat aat att act atg tgg cta aac aat tcg 591

Ser Phe Glu Glu Arg Leu Asn Asn Ile Thr Met Trp Leu Asn Asn Ser

145 150 155

aac cca cca gtc acc ttt gca aca cta tat tgg gaa gaa cca gat gca 639

Asn Pro Pro Val Thr Phe Ala Thr Leu Tyr Trp Glu Glu Pro Asp Ala

160 165 170 175

agt ggc cac aaa tac gga cct gaa gat aaa gaa aac atg agc aga gtg 687

Ser Gly His Lys Tyr Gly Pro Glu Asp Lys Glu Asn Met Ser Arg Val

180 185 190

ttg aaa aaa ata gat gat ctt atc ggt gac tta gtc caa aga ctc aag 735

Leu Lys Lys Ile Asp Asp Leu Ile Gly Asp Leu Val Gln Arg Leu Lys

195 200 205

atg tta ggg cta tgg gaa aat ctt aat gtg atc att aca agt gat cat 783

Met Leu Gly Leu Trp Glu Asn Leu Asn Val Ile Ile Thr Ser Asp His

210 215 220

ggg atg acc cag tgt tct cag gac aga ctg ata aac ctg gat tcc tgc 831

Gly Met Thr Gln Cys Ser Gln Asp Arg Leu Ile Asn Leu Asp Ser Cys

225 230 235

atc gat cat tca tac tac act ctt ata gat ttg agc cca gtt gct gca 879

Ile Asp His Ser Tyr Tyr Thr Leu Ile Asp Leu Ser Pro Val Ala Ala

240 245 250 255

ata ctt ccc aaa ata aat aga aca gag gtt tat aac aaa ctg aaa aac 927

Ile Leu Pro Lys Ile Asn Arg Thr Glu Val Tyr Asn Lys Leu Lys Asn

260 265 270

tgt agc cct cat atg aat gtt tat ctc aaa gaa gac att cct aac aga 975

Cys Ser Pro His Met Asn Val Tyr Leu Lys Glu Asp Ile Pro Asn Arg

275 280 285

ttt tat tac caa cat aat gat cga att cag ccc att att ttg gtt gcc 1023

Phe Tyr Tyr Gln His Asn Asp Arg Ile Gln Pro Ile Ile Leu Val Ala

290 295 300

gat gaa ggc tgg aca att gtg cta aat gaa tca tca caa aaa tta ggt 1071

Asp Glu Gly Trp Thr Ile Val Leu Asn Glu Ser Ser Gln Lys Leu Gly

305 310 315

gac cat ggt tat gat aat tct ttg cct agt atg cat cca ttt cta gct 1119

Asp His Gly Tyr Asp Asn Ser Leu Pro Ser Met His Pro Phe Leu Ala

320 325 330 335

gcc cac gga cct gca ttt cac aaa ggc tac aag cat agc aca att aac 1167

Ala His Gly Pro Ala Phe His Lys Gly Tyr Lys His Ser Thr Ile Asn

340 345 350

att gtg gat att tat cca atg atg tgc cac atc ctg gga tta aaa cca 1215

Ile Val Asp Ile Tyr Pro Met Met Cys His Ile Leu Gly Leu Lys Pro

355 360 365

cat ccc aat aat ggg acc ttt ggt cat act aag tgc ttg tta gtt gac 1263

His Pro Asn Asn Gly Thr Phe Gly His Thr Lys Cys Leu Leu Val Asp

370 375 380

cag tgg tgc att aat ctc cca gaa gcc atc gcg att gtt atc ggt tca 1311

Gln Trp Cys Ile Asn Leu Pro Glu Ala Ile Ala Ile Val Ile Gly Ser

385 390 395

ctc ttg gtg tta acc atg cta aca tgc ctc ata ata atc atg cag aat 1359

Leu Leu Val Leu Thr Met Leu Thr Cys Leu Ile Ile Ile Met Gln Asn

400 405 410 415

aga ctt tct gta cct cgt cca ttt tct cga ctt cag cta caa gaa gat 1407

Arg Leu Ser Val Pro Arg Pro Phe Ser Arg Leu Gln Leu Gln Glu Asp

420 425 430

gat gat gat ccc tta att ggg tgacatgtgc tagggcttat acaaagtgtc 1458

Asp Asp Asp Pro Leu Ile Gly

435

tttgattaat cacaaaacta agaatacatc caaagaatag tgttgtaact atgaaaaaga 1518

atactttgaa agacaaagaa cttagactaa gcatgttaaa attattactt tgttttcctt 1578

gtgttttgtt tcggtgcatt tgctaataag ataacgctga ccatagtaaa attgttagta 1638

aatcattagg taacatcttg tggtaggaaa tcattaggta acatcaatcc taactagaaa 1698

tactaaaaat ggcttttgag aaaaatactt cctctgcttg tattttgcga tgaagatgtg 1758

atacatcttt aaatgaaaat ataccaaaat ttagtaggca tgtttttcta ataaatttat 1818

atatttgtaa agaaaacaac agaaatcttt atgcaatttg tgaattttgt atattaggga 1878

ggaaaagctt cctatatttt tatatttacc tttaattagt ttgtatctca agtaccctct 1938

tgaggtagga aatgctctgt gatggtaaat aaaattggag cagacagaaa agatatagca 1998

aatgaagaaa tattttaagg aaacctattt gaaaaaaaaa aacaaa 2044

<210> SEQ ID NO 64

<211> LENGTH: 708

<212> TYPE: PRT

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 64

Met Lys Asp Met Pro Leu Arg Ile His Val Leu Leu Gly Leu Ala Ile

-20 -15 -10

Thr Thr Leu Val Gln Ala Val Asp Lys Lys Val Asp Cys Pro Arg Leu

-5 -1 1 5 10

Cys Thr Cys Glu Ile Arg Pro Trp Phe Thr Pro Arg Ser Ile Tyr Met

15 20 25

Glu Ala Ser Thr Val Asp Cys Asn Asp Leu Gly Leu Leu Thr Phe Pro

30 35 40

Ala Arg Leu Pro Ala Asn Thr Gln Ile Leu Leu Leu Gln Thr Asn Asn

45 50 55

Ile Ala Lys Ile Glu Tyr Ser Thr Asp Phe Pro Val Asn Leu Thr Gly

60 65 70

Leu Asp Leu Ser Gln Asn Asn Leu Ser Ser Val Thr Asn Ile Asn Val

75 80 85 90

Lys Lys Met Pro Gln Leu Leu Ser Val Tyr Leu Glu Glu Asn Lys Leu

95 100 105

Thr Glu Leu Pro Glu Lys Cys Leu Ser Glu Leu Ser Asn Leu Gln Glu

110 115 120

Leu Tyr Ile Asn His Asn Leu Leu Ser Thr Ile Ser Pro Gly Ala Phe

125 130 135

Ile Gly Leu His Asn Leu Leu Arg Leu His Leu Asn Ser Asn Arg Leu

140 145 150

Gln Met Ile Asn Ser Lys Trp Phe Asp Ala Leu Pro Asn Leu Glu Ile

155 160 165 170

Leu Met Ile Gly Glu Asn Pro Ile Ile Arg Ile Lys Asp Met Asn Phe

175 180 185

Lys Pro Leu Ile Asn Leu Arg Ser Leu Val Ile Ala Gly Ile Asn Leu

190 195 200

Thr Glu Ile Pro Asp Asn Ala Leu Val Gly Leu Glu Asn Leu Glu Ser

205 210 215

Ile Ser Phe Tyr Asp Asn Arg Leu Ile Lys Val Pro His Val Ala Leu

220 225 230

Gln Lys Val Val Asn Leu Lys Phe Leu Asp Leu Asn Lys Asn Pro Ile

235 240 245 250

Asn Arg Ile Arg Arg Gly Asp Phe Ser Asn Met Leu His Leu Lys Glu

255 260 265

Leu Gly Ile Asn Asn Met Pro Glu Leu Ile Ser Ile Asp Ser Leu Ala

270 275 280

Val Asp Asn Leu Pro Asp Leu Arg Lys Ile Glu Ala Thr Asn Asn Pro

285 290 295

Arg Leu Ser Tyr Ile His Pro Asn Ala Phe Phe Arg Leu Pro Lys Leu

300 305 310

Glu Ser Leu Met Leu Asn Ser Asn Ala Leu Ser Ala Leu Tyr His Gly

315 320 325 330

Thr Ile Glu Ser Leu Pro Asn Leu Lys Glu Ile Ser Ile His Ser Asn

335 340 345

Pro Ile Arg Cys Asp Cys Val Ile Arg Trp Met Asn Met Asn Lys Thr

350 355 360

Asn Ile Arg Phe Met Glu Pro Asp Ser Leu Phe Cys Val Asp Pro Pro

365 370 375

Glu Phe Gln Gly Gln Asn Val Arg Gln Val His Phe Arg Asp Met Met

380 385 390

Glu Ile Cys Leu Pro Leu Ile Ala Pro Glu Ser Phe Pro Ser Asn Leu

395 400 405 410

Asn Val Glu Ala Gly Ser Tyr Val Ser Phe His Cys Arg Ala Thr Ala

415 420 425

Glu Pro Gln Pro Glu Ile Tyr Trp Ile Thr Pro Ser Gly Gln Lys Leu

430 435 440

Leu Pro Asn Thr Leu Thr Asp Lys Phe Tyr Val His Ser Glu Gly Thr

445 450 455

Leu Asp Ile Asn Gly Val Thr Pro Lys Glu Gly Gly Leu Tyr Thr Cys

460 465 470

Ile Ala Thr Asn Leu Val Gly Ala Asp Leu Lys Ser Val Met Ile Lys

475 480 485 490

Val Asp Gly Ser Phe Pro Gln Asp Asn Asn Gly Ser Leu Asn Ile Lys

495 500 505

Ile Arg Asp Ile Gln Ala Asn Ser Val Leu Val Ser Trp Lys Ala Ser

510 515 520

Ser Lys Ile Leu Lys Ser Ser Val Lys Trp Thr Ala Phe Val Lys Thr

525 530 535

Glu Asn Ser His Ala Ala Gln Ser Ala Arg Ile Pro Ser Asp Val Lys

540 545 550

Val Tyr Asn Leu Thr His Leu Asn Pro Ser Thr Glu Tyr Lys Ile Cys

555 560 565 570

Ile Asp Ile Pro Thr Ile Tyr Gln Lys Asn Arg Lys Lys Cys Val Asn

575 580 585

Val Thr Thr Lys Gly Leu His Pro Asp Gln Lys Glu Tyr Glu Lys Asn

590 595 600

Asn Thr Thr Thr Leu Met Ala Cys Leu Gly Gly Leu Leu Gly Ile Ile

605 610 615

Gly Val Ile Cys Leu Ile Ser Cys Leu Ser Pro Glu Met Asn Cys Asp

620 625 630

Gly Gly His Ser Tyr Val Arg Asn Tyr Leu Gln Lys Pro Thr Phe Ala

635 640 645 650

Leu Gly Glu Leu Tyr Pro Pro Leu Ile Asn Leu Trp Glu Ala Gly Lys

655 660 665

Glu Lys Ser Thr Ser Leu Lys Val Lys Ala Thr Val Ile Gly Leu Pro

670 675 680

Thr Asn Met Ser

685

<210> SEQ ID NO 65

<211> LENGTH: 2124

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 65

atgaaggaca tgccactccg aattcatgtg ctacttggcc tagctatcac tacactagta 60

caagctgtag ataaaaaagt ggattgtcca cggttatgta cgtgtgaaat caggccttgg 120

tttacaccca gatccattta tatggaagca tctacagtgg attgtaatga tttaggtctt 180

ttaactttcc cagccagatt gccagctaac acacagattc ttctcctaca gactaacaat 240

attgcaaaaa ttgaatactc cacagacttt ccagtaaacc ttactggcct ggatttatct 300

caaaacaatt tatcttcagt caccaatatt aatgtaaaaa agatgcctca gctcctttct 360

gtgtacctag aggaaaacaa acttactgaa ctgcctgaaa aatgtctgtc cgaactgagc 420

aacttacaag aactctatat taatcacaac ttgctttcta caatttcacc tggagccttt 480

attggcctac ataatcttct tcgacttcat ctcaattcaa atagattgca gatgatcaac 540

agtaagtggt ttgatgctct tccaaatcta gagattctga tgattgggga aaatccaatt 600

atcagaatca aagacatgaa ctttaagcct cttatcaatc ttcgcagcct ggttatagct 660

ggtataaacc tcacagaaat accagataac gccttggttg gactggaaaa cttagaaagc 720

atctcttttt acgataacag gcttattaaa gtaccccatg ttgctcttca aaaagttgta 780

aatctcaaat ttttggatct aaataaaaat cctattaata gaatacgaag gggtgatttt 840

agcaatatgc tacacttaaa agagttgggg ataaataata tgcctgagct gatttccatc 900

gatagtcttg ctgtggataa cctgccagat ttaagaaaaa tagaagctac taacaaccct 960

agattgtctt acattcaccc caatgcattt ttcagactcc ccaagctgga atcactcatg 1020

ctgaacagca atgctctcag tgccctgtac catggtacca ttgagtctct gccaaacctc 1080

aaggaaatca gcatacacag taaccccatc aggtgtgact gtgtcatccg ttggatgaac 1140

atgaacaaaa ccaacattcg attcatggag ccagattcac tgttttgcgt ggacccacct 1200

gaattccaag gtcagaatgt tcggcaagtg catttcaggg acatgatgga aatttgtctc 1260

cctcttatag ctcctgagag ctttccttct aatctaaatg tagaagctgg gagctatgtt 1320

tcctttcact gtagagctac tgcagaacca cagcctgaaa tctactggat aacaccttct 1380

ggtcaaaaac tcttgcctaa taccctgaca gacaagttct atgtccattc tgagggaaca 1440

ctagatataa atggcgtaac tcccaaagaa gggggtttat atacttgtat agcaactaac 1500

ctagttggcg ctgacttgaa gtctgttatg atcaaagtgg atggatcttt tccacaagat 1560

aacaatggct ctttgaatat taaaataaga gatattcagg ccaattcagt tttggtgtcc 1620

tggaaagcaa gttctaaaat tctcaaatct agtgttaaat ggacagcctt tgtcaagact 1680

gaaaattctc atgctgcgca aagtgctcga ataccatctg atgtcaaggt atataatctt 1740

actcatctga atccatcaac tgagtataaa atttgtattg atattcccac catctatcag 1800

aaaaacagaa aaaaatgtgt aaatgtcacc accaaaggtt tgcaccctga tcaaaaagag 1860

tatgaaaaga ataataccac aacacttatg gcctgtcttg gaggccttct ggggattatt 1920

ggtgtgatat gtcttatcag ctgcctctct ccagaaatga actgtgatgg tggacacagc 1980

tatgtgagga attacttaca gaaaccaacc tttgcattag gtgagcttta tcctcctctg 2040

ataaatctct gggaagcagg aaaagaaaaa agtacatcac tgaaagtaaa agcaactgtt 2100

ataggtttac caacaaatat gtcc 2124

<210> SEQ ID NO 66

<211> LENGTH: 3068

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<220> FEATURE:

<221> NAME/KEY: sig_peptide

<222> LOCATION: (894)..(959)

<221> NAME/KEY: mat_peptide

<222> LOCATION: (960)..(3017)

<221> NAME/KEY: CDS

<222> LOCATION: (894)..(3017)

<400> SEQUENCE: 66

gtctgaagcg attggctcct ctctggggag tggagggtgt tcagttatta atgaccgctg 60

agcaggcagc accatgtcag tgtgacaact gatcgggtga acgatgcacc actaaccacc 120

atggaaacaa ggaaaaataa agccagctca caggatctct cttcactgga ttgagagcct 180

cagcctgccg actgagaaaa agagttccag gaaaaagaag gaatcccggc tgcagcctcc 240

tgccttcctt tatattttaa aatagagaga taagattgcg tgcatgtgtg catatctata 300

gtatatattt tgtacacttt gttacacaga cacacaaatg cacctattta taccgggcaa 360

gaacacaacc atgtgattat ctcaaccaag gaactgagga atccagcacg caaggacatc 420

ggaggtgggc tagcactgaa actgcttttc aagacgagga agaggaggag aaagagaaag 480

aagaggaaga tgttgggcaa catttattta acatgctcca cagcccggac cctggcatca 540

tgctgctatt cctgcaaata ctgaagaagc atgggattta aatattttac ttctaaataa 600

atgaattact caatctccta tgaccatcta tacatactcc accttcaaaa agtacatcaa 660

tattatatca ttaaggaaat agtaaccttc tcttctccaa tatgcatgac atttttggac 720

aatgcaattg tggcactggc acttatttca gtgaagaaaa actttgtggt tctatggcat 780

tcatcatttg acaaatgcaa gcatcttcct tatcaatcag ctcctattga acttactagc 840

actgactgtg gaatccttaa gggcccatta catttctgaa gaagaaagct aag atg 896

Met

aag gac atg cca ctc cga att cat gtg cta ctt ggc cta gct atc act 944

Lys Asp Met Pro Leu Arg Ile His Val Leu Leu Gly Leu Ala Ile Thr

-20 -15 -10

aca cta gta caa gct gta gat aaa aaa gtg gat tgt cca cgg tta tgt 992

Thr Leu Val Gln Ala Val Asp Lys Lys Val Asp Cys Pro Arg Leu Cys

-5 -1 1 5 10

acg tgt gaa atc agg cct tgg ttt aca ccc aga tcc att tat atg gaa 1040

Thr Cys Glu Ile Arg Pro Trp Phe Thr Pro Arg Ser Ile Tyr Met Glu

15 20 25

gca tct aca gtg gat tgt aat gat tta ggt ctt tta act ttc cca gcc 1088

Ala Ser Thr Val Asp Cys Asn Asp Leu Gly Leu Leu Thr Phe Pro Ala

30 35 40

aga ttg cca gct aac aca cag att ctt ctc cta cag act aac aat att 1136

Arg Leu Pro Ala Asn Thr Gln Ile Leu Leu Leu Gln Thr Asn Asn Ile

45 50 55

gca aaa att gaa tac tcc aca gac ttt cca gta aac ctt act ggc ctg 1184

Ala Lys Ile Glu Tyr Ser Thr Asp Phe Pro Val Asn Leu Thr Gly Leu

60 65 70 75

gat tta tct caa aac aat tta tct tca gtc acc aat att aat gta aaa 1232

Asp Leu Ser Gln Asn Asn Leu Ser Ser Val Thr Asn Ile Asn Val Lys

80 85 90

aag atg cct cag ctc ctt tct gtg tac cta gag gaa aac aaa ctt act 1280

Lys Met Pro Gln Leu Leu Ser Val Tyr Leu Glu Glu Asn Lys Leu Thr

95 100 105

gaa ctg cct gaa aaa tgt ctg tcc gaa ctg agc aac tta caa gaa ctc 1328

Glu Leu Pro Glu Lys Cys Leu Ser Glu Leu Ser Asn Leu Gln Glu Leu

110 115 120

tat att aat cac aac ttg ctt tct aca att tca cct gga gcc ttt att 1376

Tyr Ile Asn His Asn Leu Leu Ser Thr Ile Ser Pro Gly Ala Phe Ile

125 130 135

ggc cta cat aat ctt ctt cga ctt cat ctc aat tca aat aga ttg cag 1424

Gly Leu His Asn Leu Leu Arg Leu His Leu Asn Ser Asn Arg Leu Gln

140 145 150 155

atg atc aac agt aag tgg ttt gat gct ctt cca aat cta gag att ctg 1472

Met Ile Asn Ser Lys Trp Phe Asp Ala Leu Pro Asn Leu Glu Ile Leu

160 165 170

atg att ggg gaa aat cca att atc aga atc aaa gac atg aac ttt aag 1520

Met Ile Gly Glu Asn Pro Ile Ile Arg Ile Lys Asp Met Asn Phe Lys

175 180 185

cct ctt atc aat ctt cgc agc ctg gtt ata gct ggt ata aac ctc aca 1568

Pro Leu Ile Asn Leu Arg Ser Leu Val Ile Ala Gly Ile Asn Leu Thr

190 195 200

gaa ata cca gat aac gcc ttg gtt gga ctg gaa aac tta gaa agc atc 1616

Glu Ile Pro Asp Asn Ala Leu Val Gly Leu Glu Asn Leu Glu Ser Ile

205 210 215

tct ttt tac gat aac agg ctt att aaa gta ccc cat gtt gct ctt caa 1664

Ser Phe Tyr Asp Asn Arg Leu Ile Lys Val Pro His Val Ala Leu Gln

220 225 230 235

aaa gtt gta aat ctc aaa ttt ttg gat cta aat aaa aat cct att aat 1712

Lys Val Val Asn Leu Lys Phe Leu Asp Leu Asn Lys Asn Pro Ile Asn

240 245 250

aga ata cga agg ggt gat ttt agc aat atg cta cac tta aaa gag ttg 1760

Arg Ile Arg Arg Gly Asp Phe Ser Asn Met Leu His Leu Lys Glu Leu

255 260 265

ggg ata aat aat atg cct gag ctg att tcc atc gat agt ctt gct gtg 1808

Gly Ile Asn Asn Met Pro Glu Leu Ile Ser Ile Asp Ser Leu Ala Val

270 275 280

gat aac ctg cca gat tta aga aaa ata gaa gct act aac aac cct aga 1856

Asp Asn Leu Pro Asp Leu Arg Lys Ile Glu Ala Thr Asn Asn Pro Arg

285 290 295

ttg tct tac att cac ccc aat gca ttt ttc aga ctc ccc aag ctg gaa 1904

Leu Ser Tyr Ile His Pro Asn Ala Phe Phe Arg Leu Pro Lys Leu Glu

300 305 310 315

tca ctc atg ctg aac agc aat gct ctc agt gcc ctg tac cat ggt acc 1952

Ser Leu Met Leu Asn Ser Asn Ala Leu Ser Ala Leu Tyr His Gly Thr

320 325 330

att gag tct ctg cca aac ctc aag gaa atc agc ata cac agt aac ccc 2000

Ile Glu Ser Leu Pro Asn Leu Lys Glu Ile Ser Ile His Ser Asn Pro

335 340 345

atc agg tgt gac tgt gtc atc cgt tgg atg aac atg aac aaa acc aac 2048

Ile Arg Cys Asp Cys Val Ile Arg Trp Met Asn Met Asn Lys Thr Asn

350 355 360

att cga ttc atg gag cca gat tca ctg ttt tgc gtg gac cca cct gaa 2096

Ile Arg Phe Met Glu Pro Asp Ser Leu Phe Cys Val Asp Pro Pro Glu

365 370 375

ttc caa ggt cag aat gtt cgg caa gtg cat ttc agg gac atg atg gaa 2144

Phe Gln Gly Gln Asn Val Arg Gln Val His Phe Arg Asp Met Met Glu

380 385 390 395

att tgt ctc cct ctt ata gct cct gag agc ttt cct tct aat cta aat 2192

Ile Cys Leu Pro Leu Ile Ala Pro Glu Ser Phe Pro Ser Asn Leu Asn

400 405 410

gta gaa gct ggg agc tat gtt tcc ttt cac tgt aga gct act gca gaa 2240

Val Glu Ala Gly Ser Tyr Val Ser Phe His Cys Arg Ala Thr Ala Glu

415 420 425

cca cag cct gaa atc tac tgg ata aca cct tct ggt caa aaa ctc ttg 2288

Pro Gln Pro Glu Ile Tyr Trp Ile Thr Pro Ser Gly Gln Lys Leu Leu

430 435 440

cct aat acc ctg aca gac aag ttc tat gtc cat tct gag gga aca cta 2336

Pro Asn Thr Leu Thr Asp Lys Phe Tyr Val His Ser Glu Gly Thr Leu

445 450 455

gat ata aat ggc gta act ccc aaa gaa ggg ggt tta tat act tgt ata 2384

Asp Ile Asn Gly Val Thr Pro Lys Glu Gly Gly Leu Tyr Thr Cys Ile

460 465 470 475

gca act aac cta gtt ggc gct gac ttg aag tct gtt atg atc aaa gtg 2432

Ala Thr Asn Leu Val Gly Ala Asp Leu Lys Ser Val Met Ile Lys Val

480 485 490

gat gga tct ttt cca caa gat aac aat ggc tct ttg aat att aaa ata 2480

Asp Gly Ser Phe Pro Gln Asp Asn Asn Gly Ser Leu Asn Ile Lys Ile

495 500 505

aga gat att cag gcc aat tca gtt ttg gtg tcc tgg aaa gca agt tct 2528

Arg Asp Ile Gln Ala Asn Ser Val Leu Val Ser Trp Lys Ala Ser Ser

510 515 520

aaa att ctc aaa tct agt gtt aaa tgg aca gcc ttt gtc aag act gaa 2576

Lys Ile Leu Lys Ser Ser Val Lys Trp Thr Ala Phe Val Lys Thr Glu

525 530 535

aat tct cat gct gcg caa agt gct cga ata cca tct gat gtc aag gta 2624

Asn Ser His Ala Ala Gln Ser Ala Arg Ile Pro Ser Asp Val Lys Val

540 545 550 555

tat aat ctt act cat ctg aat cca tca act gag tat aaa att tgt att 2672

Tyr Asn Leu Thr His Leu Asn Pro Ser Thr Glu Tyr Lys Ile Cys Ile

560 565 570

gat att ccc acc atc tat cag aaa aac aga aaa aaa tgt gta aat gtc 2720

Asp Ile Pro Thr Ile Tyr Gln Lys Asn Arg Lys Lys Cys Val Asn Val

575 580 585

acc acc aaa ggt ttg cac cct gat caa aaa gag tat gaa aag aat aat 2768

Thr Thr Lys Gly Leu His Pro Asp Gln Lys Glu Tyr Glu Lys Asn Asn

590 595 600

acc aca aca ctt atg gcc tgt ctt gga ggc ctt ctg ggg att att ggt 2816

Thr Thr Thr Leu Met Ala Cys Leu Gly Gly Leu Leu Gly Ile Ile Gly

605 610 615

gtg ata tgt ctt atc agc tgc ctc tct cca gaa atg aac tgt gat ggt 2864

Val Ile Cys Leu Ile Ser Cys Leu Ser Pro Glu Met Asn Cys Asp Gly

620 625 630 635

gga cac agc tat gtg agg aat tac tta cag aaa cca acc ttt gca tta 2912

Gly His Ser Tyr Val Arg Asn Tyr Leu Gln Lys Pro Thr Phe Ala Leu

640 645 650

ggt gag ctt tat cct cct ctg ata aat ctc tgg gaa gca gga aaa gaa 2960

Gly Glu Leu Tyr Pro Pro Leu Ile Asn Leu Trp Glu Ala Gly Lys Glu

655 660 665

aaa agt aca tca ctg aaa gta aaa gca act gtt ata ggt tta cca aca 3008

Lys Ser Thr Ser Leu Lys Val Lys Ala Thr Val Ile Gly Leu Pro Thr

670 675 680

aat atg tcc taaaaaccac caaggaaacc tactccaaaa atgaacaaaa 3057

Asn Met Ser

685

aaaaaaaaaa a 3068

<210> SEQ ID NO 67

<211> LENGTH: 255

<212> TYPE: PRT

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 67

Met Ser Tyr Tyr Gly Ser Ser Tyr His Ile Ile Asn Ala Asp Ala Lys

1 5 10 15

Tyr Pro Gly Tyr Pro Pro Glu His Ile Ile Ala Glu Lys Arg Arg Ala

20 25 30

Arg Arg Arg Leu Leu His Lys Asp Gly Ser Cys Asn Val Tyr Phe Lys

35 40 45

His Ile Phe Gly Glu Trp Gly Ser Tyr Val Val Asp Ile Phe Thr Thr

50 55 60

Leu Val Asp Thr Lys Trp Arg His Met Phe Val Ile Phe Ser Leu Ser

65 70 75 80

Tyr Ile Leu Ser Trp Leu Ile Phe Gly Ser Val Phe Trp Leu Ile Ala

85 90 95

Phe His His Gly Asp Leu Leu Asn Asp Pro Asp Ile Thr Pro Cys Val

100 105 110

Asp Asn Val His Ser Phe Thr Gly Ala Phe Leu Phe Ser Leu Glu Thr

115 120 125

Gln Thr Thr Ile Gly Tyr Gly Tyr Arg Cys Val Thr Glu Glu Cys Ser

130 135 140

Val Ala Val Leu Met Val Ile Leu Gln Ser Ile Leu Ser Cys Ile Ile

145 150 155 160

Asn Thr Phe Ile Ile Gly Ala Ala Leu Ala Lys Met Ala Thr Ala Arg

165 170 175

Lys Arg Ala Gln Thr Ile Arg Phe Ser Tyr Phe Ala Leu Ile Gly Met

180 185 190

Arg Asp Gly Lys Leu Cys Leu Met Trp Arg Ile Gly Asp Phe Arg Pro

195 200 205

Asn His Val Val Glu Gly Thr Val Arg Ala Gln Leu Leu Arg Tyr Thr

210 215 220

Glu Asp Ser Glu Gly Arg Met Thr Met Ala Phe Lys Asp Leu Lys Leu

225 230 235 240

Val Asn Asp Gln Ile Ile Leu Val Thr Pro Val Thr Ile Val Pro

245 250 255

<210> SEQ ID NO 68

<211> LENGTH: 765

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 68

atgagctatt acggcagcag ctatcatatt atcaatgcgg acgcaaaata cccaggctac 60

ccgccagagc acattatagc tgagaagaga agagcaagaa gacgattact tcacaaagat 120

ggcagctgta atgtctactt caagcacatt tttggagaat ggggaagcta tgtggttgac 180

atcttcacca ctcttgtgga caccaagtgg cgccatatgt ttgtgatatt ttctttatct 240

tatattctct cgtggttgat atttggctct gtcttttggc tcatagcctt tcatcatggc 300

gatctattaa atgatccaga catcacacct tgtgttgaca acgtccattc tttcacaggg 360

gcctttttgt tctccctaga gacccaaacc accataggat atggttatcg ctgtgttact 420

gaagaatgtt ctgtggccgt gctcatggtg atcctccagt ccatcttaag ttgcatcata 480

aataccttta tcattggagc tgccttggcc aaaatggcaa ctgctcgaaa gagagcccaa 540

accattcgtt tcagctactt tgcacttata ggtatgagag atgggaagct ttgcctcatg 600

tggcgcattg gtgattttcg gccaaaccac gtggtagaag gaacagttag agcccaactt 660

ctccgctata cagaagacag tgaagggagg atgacgatgg catttaaaga cctcaaatta 720

gtcaacgacc aaatcatcct ggtcaccccg gtaactattg tccca 765

<210> SEQ ID NO 69

<211> LENGTH: 907

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<220> FEATURE:

<221> NAME/KEY: CDS

<222> LOCATION: (78)..(842)

<400> SEQUENCE: 69

caaaccaaga aatagcaaca agtctagaat tcttactact acaaaactca cctggatccc 60

taagggcaca gcaaaga atg agc tat tac ggc agc agc tat cat att atc 110

Met Ser Tyr Tyr Gly Ser Ser Tyr His Ile Ile

1 5 10

aat gcg gac gca aaa tac cca ggc tac ccg cca gag cac att ata gct 158

Asn Ala Asp Ala Lys Tyr Pro Gly Tyr Pro Pro Glu His Ile Ile Ala

15 20 25

gag aag aga aga gca aga aga cga tta ctt cac aaa gat ggc agc tgt 206

Glu Lys Arg Arg Ala Arg Arg Arg Leu Leu His Lys Asp Gly Ser Cys

30 35 40

aat gtc tac ttc aag cac att ttt gga gaa tgg gga agc tat gtg gtt 254

Asn Val Tyr Phe Lys His Ile Phe Gly Glu Trp Gly Ser Tyr Val Val

45 50 55

gac atc ttc acc act ctt gtg gac acc aag tgg cgc cat atg ttt gtg 302

Asp Ile Phe Thr Thr Leu Val Asp Thr Lys Trp Arg His Met Phe Val

60 65 70 75

ata ttt tct tta tct tat att ctc tcg tgg ttg ata ttt ggc tct gtc 350

Ile Phe Ser Leu Ser Tyr Ile Leu Ser Trp Leu Ile Phe Gly Ser Val

80 85 90

ttt tgg ctc ata gcc ttt cat cat ggc gat cta tta aat gat cca gac 398

Phe Trp Leu Ile Ala Phe His His Gly Asp Leu Leu Asn Asp Pro Asp

95 100 105

atc aca cct tgt gtt gac aac gtc cat tct ttc aca ggg gcc ttt ttg 446

Ile Thr Pro Cys Val Asp Asn Val His Ser Phe Thr Gly Ala Phe Leu

110 115 120

ttc tcc cta gag acc caa acc acc ata gga tat ggt tat cgc tgt gtt 494

Phe Ser Leu Glu Thr Gln Thr Thr Ile Gly Tyr Gly Tyr Arg Cys Val

125 130 135

act gaa gaa tgt tct gtg gcc gtg ctc atg gtg atc ctc cag tcc atc 542

Thr Glu Glu Cys Ser Val Ala Val Leu Met Val Ile Leu Gln Ser Ile

140 145 150 155

tta agt tgc atc ata aat acc ttt atc att gga gct gcc ttg gcc aaa 590

Leu Ser Cys Ile Ile Asn Thr Phe Ile Ile Gly Ala Ala Leu Ala Lys

160 165 170

atg gca act gct cga aag aga gcc caa acc att cgt ttc agc tac ttt 638

Met Ala Thr Ala Arg Lys Arg Ala Gln Thr Ile Arg Phe Ser Tyr Phe

175 180 185

gca ctt ata ggt atg aga gat ggg aag ctt tgc ctc atg tgg cgc att 686

Ala Leu Ile Gly Met Arg Asp Gly Lys Leu Cys Leu Met Trp Arg Ile

190 195 200

ggt gat ttt cgg cca aac cac gtg gta gaa gga aca gtt aga gcc caa 734

Gly Asp Phe Arg Pro Asn His Val Val Glu Gly Thr Val Arg Ala Gln

205 210 215

ctt ctc cgc tat aca gaa gac agt gaa ggg agg atg acg atg gca ttt 782

Leu Leu Arg Tyr Thr Glu Asp Ser Glu Gly Arg Met Thr Met Ala Phe

220 225 230 235

aaa gac ctc aaa tta gtc aac gac caa atc atc ctg gtc acc ccg gta 830

Lys Asp Leu Lys Leu Val Asn Asp Gln Ile Ile Leu Val Thr Pro Val

240 245 250

act att gtc cca tgaccctgcc aaatccccct ctgtgagaaa cacccaaaaa 882

Thr Ile Val Pro

255

aaaaaaaaaa aaaaaaaaaa aaaaa 907

<210> SEQ ID NO 70

<211> LENGTH: 859

<212> TYPE: PRT

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 70

Met Ala Cys Arg Trp Ser Thr Lys Glu Ser Pro Arg Trp Arg Ser Ala

-25 -20 -15

Leu Leu Leu Leu Phe Leu Ala Gly Val Tyr Gly Asn Gly Ala Leu Ala

-10 -5 -1 1 5

Glu His Ser Glu Asn Val His Ile Ser Gly Val Ser Thr Ala Cys Gly

10 15 20

Glu Thr Pro Glu Gln Ile Arg Ala Pro Ser Gly Ile Ile Thr Ser Pro

25 30 35

Gly Trp Pro Ser Glu Tyr Pro Ala Lys Ile Asn Cys Ser Trp Phe Ile

40 45 50

Arg Ala Asn Pro Gly Glu Ile Ile Thr Ile Ser Phe Gln Asp Phe Asp

55 60 65

Ile Gln Gly Ser Arg Arg Cys Asn Leu Asp Trp Leu Thr Ile Glu Thr

70 75 80 85

Tyr Lys Asn Ile Glu Ser Tyr Arg Ala Cys Gly Ser Thr Ile Pro Pro

90 95 100

Pro Tyr Ile Ser Ser Gln Asp His Ile Trp Ile Arg Phe His Ser Asp

105 110 115

Asp Asn Ile Ser Arg Lys Gly Phe Arg Leu Ala Tyr Phe Ser Gly Lys

120 125 130

Ser Glu Glu Pro Asn Cys Ala Cys Asp Gln Phe Arg Cys Gly Asn Gly

135 140 145

Lys Cys Ile Pro Glu Ala Trp Lys Cys Asn Asn Met Asp Glu Cys Gly

150 155 160 165

Asp Ser Ser Asp Glu Glu Ile Cys Ala Lys Glu Ala Asn Pro Pro Thr

170 175 180

Ala Ala Ala Phe Gln Pro Cys Ala Tyr Asn Gln Phe Gln Cys Leu Ser

185 190 195

Arg Phe Thr Lys Val Tyr Thr Cys Leu Pro Glu Ser Leu Lys Cys Asp

200 205 210

Gly Asn Ile Asp Cys Leu Asp Leu Gly Asp Glu Ile Asp Cys Asp Val

215 220 225

Pro Thr Cys Gly Gln Trp Leu Lys Tyr Phe Tyr Gly Thr Phe Asn Ser

230 235 240 245

Pro Asn Tyr Pro Asp Phe Tyr Pro Pro Gly Ser Asn Cys Thr Trp Leu

250 255 260

Ile Asp Thr Gly Asp His Arg Lys Val Ile Leu Arg Phe Thr Asp Phe

265 270 275

Lys Leu Asp Gly Thr Gly Tyr Gly Asp Tyr Val Lys Ile Tyr Asp Gly

280 285 290

Leu Glu Glu Asn Pro His Lys Leu Leu Arg Val Leu Thr Ala Phe Asp

295 300 305

Ser His Ala Pro Leu Thr Val Val Ser Ser Ser Gly Gln Ile Arg Val

310 315 320 325

His Phe Cys Ala Asp Lys Val Asn Ala Ala Arg Gly Phe Asn Ala Thr

330 335 340

Tyr Gln Val Asp Gly Phe Cys Leu Pro Trp Glu Ile Pro Cys Gly Gly

345 350 355

Asn Trp Gly Cys Tyr Thr Glu Gln Gln Arg Cys Asp Gly Tyr Trp His

360 365 370

Cys Pro Asn Gly Arg Asp Glu Thr Asn Cys Thr Met Cys Gln Lys Glu

375 380 385

Glu Phe Pro Cys Ser Arg Asn Gly Val Cys Tyr Pro Arg Ser Asp Arg

390 395 400 405

Cys Asn Tyr Gln Asn His Cys Pro Asn Gly Ser Asp Glu Lys Asn Cys

410 415 420

Phe Phe Cys Gln Pro Gly Asn Phe His Cys Lys Asn Asn Arg Cys Val

425 430 435

Phe Glu Ser Trp Val Cys Asp Ser Gln Asp Asp Cys Gly Asp Gly Ser

440 445 450

Asp Glu Glu Asn Cys Pro Val Ile Val Pro Thr Arg Val Ile Thr Ala

455 460 465

Ala Val Ile Gly Ser Leu Ile Cys Gly Leu Leu Leu Val Ile Ala Leu

470 475 480 485

Gly Cys Thr Cys Lys Leu Tyr Ser Leu Arg Met Phe Glu Arg Arg Ser

490 495 500

Phe Glu Thr Gln Leu Ser Arg Val Glu Ala Glu Leu Leu Arg Arg Glu

505 510 515

Ala Pro Pro Ser Tyr Gly Gln Leu Ile Ala Gln Gly Leu Ile Pro Pro

520 525 530

Val Glu Asp Phe Pro Val Cys Ser Pro Asn Gln Ala Ser Val Leu Glu

535 540 545

Asn Leu Arg Leu Ala Val Arg Ser Gln Leu Gly Phe Thr Ser Val Arg

550 555 560 565

Leu Pro Met Ala Gly Arg Ser Ser Asn Ile Trp Asn Arg Ile Phe Asn

570 575 580

Phe Ala Arg Ser Arg His Ser Gly Ser Leu Ala Leu Val Ser Ala Asp

585 590 595

Gly Asp Glu Val Val Pro Ser Gln Ser Thr Ser Arg Glu Pro Glu Arg

600 605 610

Asn His Thr His Arg Ser Leu Phe Ser Val Glu Ser Asp Asp Thr Asp

615 620 625

Thr Glu Asn Glu Arg Arg Asp Met Ala Gly Ala Ser Gly Gly Val Ala

630 635 640 645

Ala Pro Leu Pro Gln Lys Val Pro Pro Thr Thr Ala Val Glu Ala Thr

650 655 660

Val Gly Ala Cys Ala Ser Ser Ser Thr Gln Ser Thr Arg Gly Gly His

665 670 675

Ala Asp Asn Gly Arg Asp Val Thr Ser Val Glu Pro Pro Ser Val Ser

680 685 690

Pro Ala Arg His Gln Leu Thr Ser Ala Leu Ser Arg Met Thr Gln Gly

695 700 705

Leu Arg Trp Val Arg Phe Thr Leu Gly Arg Ser Ser Ser Leu Ser Gln

710 715 720 725

Asn Gln Ser Pro Leu Arg Gln Leu Asp Asn Gly Val Ser Gly Arg Glu

730 735 740

Asp Asp Asp Asp Val Glu Met Leu Ile Pro Ile Ser Asp Gly Ser Ser

745 750 755

Asp Phe Asp Val Asn Asp Cys Ser Arg Pro Leu Leu Asp Leu Ala Ser

760 765 770

Asp Gln Gly Gln Gly Leu Arg Gln Pro Tyr Asn Ala Thr Asn Pro Gly

775 780 785

Val Arg Pro Ser Asn Arg Asp Gly Pro Cys Glu Arg Cys Gly Ile Val

790 795 800 805

His Thr Ala Gln Ile Pro Asp Thr Cys Leu Glu Val Thr Leu Lys Asn

810 815 820

Glu Thr Ser Asp Asp Glu Ala Leu Leu Leu Cys

825 830

<210> SEQ ID NO 71

<211> LENGTH: 2577

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 71

atggcctgtc gctggagcac aaaagagtct ccgcggtgga ggtctgcgtt gctcttgctt 60

ttcctcgctg gggtgtacgg aaatggtgct cttgcagaac attctgaaaa tgtgcatatt 120

tcaggagtgt caactgcttg tggagagact ccagagcaaa tacgagcacc aagtggcata 180

atcacaagcc caggctggcc ttctgaatat cctgcaaaaa tcaactgtag ctggttcata 240

agggcaaacc caggcgaaat cattactata agttttcagg attttgatat tcaaggatcc 300

agaaggtgca atttggactg gttgacaata gaaacataca agaatattga aagttacaga 360

gcttgtggtt ccacaattcc acctccgtat atctcttcac aagaccacat ctggattagg 420

tttcattcgg atgacaacat ctctagaaag ggtttcagac tggcatattt ttcagggaaa 480

tctgaggaac caaattgtgc ttgtgatcag tttcgttgtg gtaatggaaa gtgtatacca 540

gaagcctgga aatgtaataa catggatgaa tgtggagata gttccgatga agagatctgt 600

gccaaagaag caaatcctcc aactgctgct gcttttcaac cctgtgctta caaccagttc 660

cagtgtttat cccgttttac caaagtttac acttgcctcc ccgaatcttt aaaatgtgat 720

gggaacattg actgccttga cctaggagat gagatagact gtgatgtgcc aacatgtggg 780

caatggctaa aatattttta tggtactttt aattctccca attatccaga cttttatcct 840

cctggaagca attgcacctg gttaatagac actggtgatc accgtaaagt cattttacgc 900

ttcactgact ttaaacttga tggtactggt tatggtgatt atgtcaaaat atatgatgga 960

ttagaggaga atccacacaa gcttttgcgt gtgttgacag cttttgattc tcatgcacct 1020

cttacagttg tttcttcttc tggacagata agggtacatt tttgtgctga taaagtgaat 1080

gctgcaaggg gatttaatgc tacttaccaa gtagatgggt tctgtttgcc atgggaaata 1140

ccctgtggag gtaactgggg gtgttatact gagcagcagc gttgtgatgg gtattggcat 1200

tgcccaaatg gaagggatga aaccaattgt accatgtgcc agaaggaaga atttccatgt 1260

tcccgaaatg gtgtctgtta tcctcgttct gatcgctgca actaccagaa tcattgccca 1320

aatggctcag atgaaaaaaa ctgctttttt tgccaaccag gaaatttcca ttgtaaaaac 1380

aatcgttgtg tgtttgaaag ttgggtgtgt gattctcaag atgactgtgg tgatggcagc 1440

gatgaagaaa attgcccagt aatcgtgcct acaagagtca tcactgctgc cgtcataggg 1500

agcctcatct gtggcctgtt actcgtcata gcattgggat gtacttgtaa gctttattct 1560

ctgagaatgt ttgaaagaag atcatttgaa acacagttgt caagagtgga agcagaattg 1620

ttaagaagag aagctcctcc ctcgtatgga caattgattg ctcagggttt aattccacca 1680

gttgaagatt ttcctgtttg ttcacctaat caggcttctg ttttggaaaa tctgaggcta 1740

gcggtacgat ctcagcttgg atttacttca gtcaggcttc ctatggcagg cagatcaagc 1800

aacatttgga accgtatttt taattttgca agatcacgtc attctgggtc attggctttg 1860

gtctcagcag atggagatga ggttgtccct agtcagagta ccagtagaga acctgagaga 1920

aatcatactc acagaagttt gttttccgtg gagtctgatg atacagacac agaaaatgag 1980

agaagagata tggcaggagc atctggtggg gttgcagctc ctttgcctca aaaagtccct 2040

cccacaacgg cagtagaagc gacagtagga gcatgtgcaa gttcctcaac tcagagtacc 2100

cgaggtggcc atgcagataa tggaagggat gtgacaagtg tggaaccccc aagtgtgagt 2160

ccagcacgtc accagcttac aagtgcactc agtcgtatga ctcaggggct acgctgggta 2220

cgttttacat taggacgatc aagttcccta agtcagaacc agagtccttt gagacaactt 2280

gataatgggg taagtggaag agaagatgat gatgatgttg aaatgctaat tccaatttct 2340

gatggatctt cagactttga tgtgaatgac tgctccagac ctcttcttga tcttgcctca 2400

gatcaaggac aagggcttag acaaccatat aatgcaacaa atcctggagt aaggccaagt 2460

aatcgagatg gcccctgtga gcgctgtggt attgtccaca ctgcccagat accagacact 2520

tgcttagaag taacactgaa aaacgaaacg agtgatgatg aggctttgtt actttgt 2577

<210> SEQ ID NO 72

<211> LENGTH: 3088

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<220> FEATURE:

<221> NAME/KEY: CDS

<222> LOCATION: (41)..(2617)

<221> NAME/KEY: sig_peptide

<222> LOCATION: (41)..(121)

<221> NAME/KEY: mat_peptide

<222> LOCATION: (122)..(2617)

<400> SEQUENCE: 72

ctcctccgtc tcctcctctc tctctccatc tgctgtggtt atg gcc tgt cgc tgg 55

Met Ala Cys Arg Trp

-25

agc aca aaa gag tct ccg cgg tgg agg tct gcg ttg ctc ttg ctt ttc 103

Ser Thr Lys Glu Ser Pro Arg Trp Arg Ser Ala Leu Leu Leu Leu Phe

-20 -15 -10

ctc gct ggg gtg tac gga aat ggt gct ctt gca gaa cat tct gaa aat 151

Leu Ala Gly Val Tyr Gly Asn Gly Ala Leu Ala Glu His Ser Glu Asn

-5 -1 1 5 10

gtg cat att tca gga gtg tca act gct tgt gga gag act cca gag caa 199

Val His Ile Ser Gly Val Ser Thr Ala Cys Gly Glu Thr Pro Glu Gln

15 20 25

ata cga gca cca agt ggc ata atc aca agc cca ggc tgg cct tct gaa 247

Ile Arg Ala Pro Ser Gly Ile Ile Thr Ser Pro Gly Trp Pro Ser Glu

30 35 40

tat cct gca aaa atc aac tgt agc tgg ttc ata agg gca aac cca ggc 295

Tyr Pro Ala Lys Ile Asn Cys Ser Trp Phe Ile Arg Ala Asn Pro Gly

45 50 55

gaa atc att act ata agt ttt cag gat ttt gat att caa gga tcc aga 343

Glu Ile Ile Thr Ile Ser Phe Gln Asp Phe Asp Ile Gln Gly Ser Arg

60 65 70

agg tgc aat ttg gac tgg ttg aca ata gaa aca tac aag aat att gaa 391

Arg Cys Asn Leu Asp Trp Leu Thr Ile Glu Thr Tyr Lys Asn Ile Glu

75 80 85 90

agt tac aga gct tgt ggt tcc aca att cca cct ccg tat atc tct tca 439

Ser Tyr Arg Ala Cys Gly Ser Thr Ile Pro Pro Pro Tyr Ile Ser Ser

95 100 105

caa gac cac atc tgg att agg ttt cat tcg gat gac aac atc tct aga 487

Gln Asp His Ile Trp Ile Arg Phe His Ser Asp Asp Asn Ile Ser Arg

110 115 120

aag ggt ttc aga ctg gca tat ttt tca ggg aaa tct gag gaa cca aat 535

Lys Gly Phe Arg Leu Ala Tyr Phe Ser Gly Lys Ser Glu Glu Pro Asn

125 130 135

tgt gct tgt gat cag ttt cgt tgt ggt aat gga aag tgt ata cca gaa 583

Cys Ala Cys Asp Gln Phe Arg Cys Gly Asn Gly Lys Cys Ile Pro Glu

140 145 150

gcc tgg aaa tgt aat aac atg gat gaa tgt gga gat agt tcc gat gaa 631

Ala Trp Lys Cys Asn Asn Met Asp Glu Cys Gly Asp Ser Ser Asp Glu

155 160 165 170

gag atc tgt gcc aaa gaa gca aat cct cca act gct gct gct ttt caa 679

Glu Ile Cys Ala Lys Glu Ala Asn Pro Pro Thr Ala Ala Ala Phe Gln

175 180 185

ccc tgt gct tac aac cag ttc cag tgt tta tcc cgt ttt acc aaa gtt 727

Pro Cys Ala Tyr Asn Gln Phe Gln Cys Leu Ser Arg Phe Thr Lys Val

190 195 200

tac act tgc ctc ccc gaa tct tta aaa tgt gat ggg aac att gac tgc 775

Tyr Thr Cys Leu Pro Glu Ser Leu Lys Cys Asp Gly Asn Ile Asp Cys

205 210 215

ctt gac cta gga gat gag ata gac tgt gat gtg cca aca tgt ggg caa 823

Leu Asp Leu Gly Asp Glu Ile Asp Cys Asp Val Pro Thr Cys Gly Gln

220 225 230

tgg cta aaa tat ttt tat ggt act ttt aat tct ccc aat tat cca gac 871

Trp Leu Lys Tyr Phe Tyr Gly Thr Phe Asn Ser Pro Asn Tyr Pro Asp

235 240 245 250

ttt tat cct cct gga agc aat tgc acc tgg tta ata gac act ggt gat 919

Phe Tyr Pro Pro Gly Ser Asn Cys Thr Trp Leu Ile Asp Thr Gly Asp

255 260 265

cac cgt aaa gtc att tta cgc ttc act gac ttt aaa ctt gat ggt act 967

His Arg Lys Val Ile Leu Arg Phe Thr Asp Phe Lys Leu Asp Gly Thr

270 275 280

ggt tat ggt gat tat gtc aaa ata tat gat gga tta gag gag aat cca 1015

Gly Tyr Gly Asp Tyr Val Lys Ile Tyr Asp Gly Leu Glu Glu Asn Pro

285 290 295

cac aag ctt ttg cgt gtg ttg aca gct ttt gat tct cat gca cct ctt 1063

His Lys Leu Leu Arg Val Leu Thr Ala Phe Asp Ser His Ala Pro Leu

300 305 310

aca gtt gtt tct tct tct gga cag ata agg gta cat ttt tgt gct gat 1111

Thr Val Val Ser Ser Ser Gly Gln Ile Arg Val His Phe Cys Ala Asp

315 320 325 330

aaa gtg aat gct gca agg gga ttt aat gct act tac caa gta gat ggg 1159

Lys Val Asn Ala Ala Arg Gly Phe Asn Ala Thr Tyr Gln Val Asp Gly

335 340 345

ttc tgt ttg cca tgg gaa ata ccc tgt gga ggt aac tgg ggg tgt tat 1207

Phe Cys Leu Pro Trp Glu Ile Pro Cys Gly Gly Asn Trp Gly Cys Tyr

350 355 360

act gag cag cag cgt tgt gat ggg tat tgg cat tgc cca aat gga agg 1255

Thr Glu Gln Gln Arg Cys Asp Gly Tyr Trp His Cys Pro Asn Gly Arg

365 370 375

gat gaa acc aat tgt acc atg tgc cag aag gaa gaa ttt cca tgt tcc 1303

Asp Glu Thr Asn Cys Thr Met Cys Gln Lys Glu Glu Phe Pro Cys Ser

380 385 390

cga aat ggt gtc tgt tat cct cgt tct gat cgc tgc aac tac cag aat 1351

Arg Asn Gly Val Cys Tyr Pro Arg Ser Asp Arg Cys Asn Tyr Gln Asn

395 400 405 410

cat tgc cca aat ggc tca gat gaa aaa aac tgc ttt ttt tgc caa cca 1399

His Cys Pro Asn Gly Ser Asp Glu Lys Asn Cys Phe Phe Cys Gln Pro

415 420 425

gga aat ttc cat tgt aaa aac aat cgt tgt gtg ttt gaa agt tgg gtg 1447

Gly Asn Phe His Cys Lys Asn Asn Arg Cys Val Phe Glu Ser Trp Val

430 435 440

tgt gat tct caa gat gac tgt ggt gat ggc agc gat gaa gaa aat tgc 1495

Cys Asp Ser Gln Asp Asp Cys Gly Asp Gly Ser Asp Glu Glu Asn Cys

445 450 455

cca gta atc gtg cct aca aga gtc atc act gct gcc gtc ata ggg agc 1543

Pro Val Ile Val Pro Thr Arg Val Ile Thr Ala Ala Val Ile Gly Ser

460 465 470

ctc atc tgt ggc ctg tta ctc gtc ata gca ttg gga tgt act tgt aag 1591

Leu Ile Cys Gly Leu Leu Leu Val Ile Ala Leu Gly Cys Thr Cys Lys

475 480 485 490

ctt tat tct ctg aga atg ttt gaa aga aga tca ttt gaa aca cag ttg 1639

Leu Tyr Ser Leu Arg Met Phe Glu Arg Arg Ser Phe Glu Thr Gln Leu

495 500 505

tca aga gtg gaa gca gaa ttg tta aga aga gaa gct cct ccc tcg tat 1687

Ser Arg Val Glu Ala Glu Leu Leu Arg Arg Glu Ala Pro Pro Ser Tyr

510 515 520

gga caa ttg att gct cag ggt tta att cca cca gtt gaa gat ttt cct 1735

Gly Gln Leu Ile Ala Gln Gly Leu Ile Pro Pro Val Glu Asp Phe Pro

525 530 535

gtt tgt tca cct aat cag gct tct gtt ttg gaa aat ctg agg cta gcg 1783

Val Cys Ser Pro Asn Gln Ala Ser Val Leu Glu Asn Leu Arg Leu Ala

540 545 550

gta cga tct cag ctt gga ttt act tca gtc agg ctt cct atg gca ggc 1831

Val Arg Ser Gln Leu Gly Phe Thr Ser Val Arg Leu Pro Met Ala Gly

555 560 565 570

aga tca agc aac att tgg aac cgt att ttt aat ttt gca aga tca cgt 1879

Arg Ser Ser Asn Ile Trp Asn Arg Ile Phe Asn Phe Ala Arg Ser Arg

575 580 585

cat tct ggg tca ttg gct ttg gtc tca gca gat gga gat gag gtt gtc 1927

His Ser Gly Ser Leu Ala Leu Val Ser Ala Asp Gly Asp Glu Val Val

590 595 600

cct agt cag agt acc agt aga gaa cct gag aga aat cat act cac aga 1975

Pro Ser Gln Ser Thr Ser Arg Glu Pro Glu Arg Asn His Thr His Arg

605 610 615

agt ttg ttt tcc gtg gag tct gat gat aca gac aca gaa aat gag aga 2023

Ser Leu Phe Ser Val Glu Ser Asp Asp Thr Asp Thr Glu Asn Glu Arg

620 625 630

aga gat atg gca gga gca tct ggt ggg gtt gca gct cct ttg cct caa 2071

Arg Asp Met Ala Gly Ala Ser Gly Gly Val Ala Ala Pro Leu Pro Gln

635 640 645 650

aaa gtc cct ccc aca acg gca gta gaa gcg aca gta gga gca tgt gca 2119

Lys Val Pro Pro Thr Thr Ala Val Glu Ala Thr Val Gly Ala Cys Ala

655 660 665

agt tcc tca act cag agt acc cga ggt ggc cat gca gat aat gga agg 2167

Ser Ser Ser Thr Gln Ser Thr Arg Gly Gly His Ala Asp Asn Gly Arg

670 675 680

gat gtg aca agt gtg gaa ccc cca agt gtg agt cca gca cgt cac cag 2215

Asp Val Thr Ser Val Glu Pro Pro Ser Val Ser Pro Ala Arg His Gln

685 690 695

ctt aca agt gca ctc agt cgt atg act cag ggg cta cgc tgg gta cgt 2263

Leu Thr Ser Ala Leu Ser Arg Met Thr Gln Gly Leu Arg Trp Val Arg

700 705 710

ttt aca tta gga cga tca agt tcc cta agt cag aac cag agt cct ttg 2311

Phe Thr Leu Gly Arg Ser Ser Ser Leu Ser Gln Asn Gln Ser Pro Leu

715 720 725 730

aga caa ctt gat aat ggg gta agt gga aga gaa gat gat gat gat gtt 2359

Arg Gln Leu Asp Asn Gly Val Ser Gly Arg Glu Asp Asp Asp Asp Val

735 740 745

gaa atg cta att cca att tct gat gga tct tca gac ttt gat gtg aat 2407

Glu Met Leu Ile Pro Ile Ser Asp Gly Ser Ser Asp Phe Asp Val Asn

750 755 760

gac tgc tcc aga cct ctt ctt gat ctt gcc tca gat caa gga caa ggg 2455

Asp Cys Ser Arg Pro Leu Leu Asp Leu Ala Ser Asp Gln Gly Gln Gly

765 770 775

ctt aga caa cca tat aat gca aca aat cct gga gta agg cca agt aat 2503

Leu Arg Gln Pro Tyr Asn Ala Thr Asn Pro Gly Val Arg Pro Ser Asn

780 785 790

cga gat ggc ccc tgt gag cgc tgt ggt att gtc cac act gcc cag ata 2551

Arg Asp Gly Pro Cys Glu Arg Cys Gly Ile Val His Thr Ala Gln Ile

795 800 805 810

cca gac act tgc tta gaa gta aca ctg aaa aac gaa acg agt gat gat 2599

Pro Asp Thr Cys Leu Glu Val Thr Leu Lys Asn Glu Thr Ser Asp Asp

815 820 825

gag gct ttg tta ctt tgt taggtacgaa tcacataagg gagattgtat 2647

Glu Ala Leu Leu Leu Cys

830

acaagttgga gcaatatcca tttattattt tgtaacttta cagttaaact agttttagtt 2707

taaaaagaaa aaatgcaggg tgatttctta ttattatatg ttagcctgca tggttaaatt 2767

cgacaacttg taactctatg aacttagagt ttactatttt agcagctaaa aatgcatcac 2827

atattcatat tgttcaataa tgtcctttca tttgtttctg attgttttca tcctgatact 2887

gtagttcact gtagaaatgt ggctgctgaa actcatttga ttgtcatttt tatctatcct 2947

atgttaaatg gtttgttttt acaaaataat accttatttt aattgaaacg tttatgcttt 3007

tgccaacaca tcttgtaact taatatacta gatgttaagg ttgttaatgt acaaaaaaaa 3067

aaaaaaaaaa aaaaaaaaaa a 3088

<210> SEQ ID NO 73

<211> LENGTH: 687

<212> TYPE: PRT

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 73

Met Thr Pro Gln Ser Leu Leu Gln Thr Thr Leu Phe Leu Leu Ser Leu

-25 -20 -15 -10

Leu Phe Leu Val Gln Gly Ala His Gly Arg Gly His Arg Glu Asp Phe

-5 -1 1 5

Arg Phe Cys Ser Gln Arg Asn Gln Thr His Arg Ser Ser Leu His Tyr

10 15 20

Lys Pro Thr Pro Asp Leu Arg Ile Ser Ile Glu Asn Ser Glu Glu Ala

25 30 35

Leu Thr Val His Ala Pro Phe Pro Ala Ala His Pro Ala Ser Arg Ser

40 45 50 55

Phe Pro Asp Pro Arg Gly Leu Tyr His Phe Cys Leu Tyr Trp Asn Arg

60 65 70

His Ala Gly Arg Leu His Leu Leu Tyr Gly Lys Arg Asp Phe Leu Leu

75 80 85

Ser Asp Lys Ala Ser Ser Leu Leu Cys Phe Gln His Gln Glu Glu Ser

90 95 100

Leu Ala Gln Gly Pro Pro Leu Leu Ala Thr Ser Val Thr Ser Trp Trp

105 110 115

Ser Pro Gln Asn Ile Ser Leu Pro Ser Ala Ala Ser Phe Thr Phe Ser

120 125 130 135

Phe His Ser Pro Pro His Thr Ala Ala His Asn Ala Ser Val Asp Met

140 145 150

Cys Glu Leu Lys Arg Asp Leu Gln Leu Leu Ser Gln Phe Leu Lys His

155 160 165

Pro Gln Lys Ala Ser Arg Arg Pro Ser Ala Ala Pro Ala Ser Gln Gln

170 175 180

Leu Gln Ser Leu Glu Ser Lys Leu Thr Ser Val Arg Phe Met Gly Asp

185 190 195

Met Val Ser Phe Glu Glu Asp Arg Ile Asn Ala Thr Val Trp Lys Leu

200 205 210 215

Gln Pro Thr Ala Gly Leu Gln Asp Leu His Ile His Ser Arg Gln Glu

220 225 230

Glu Glu Gln Ser Glu Ile Met Glu Tyr Ser Val Leu Leu Pro Arg Thr

235 240 245

Leu Phe Gln Arg Thr Lys Gly Arg Arg Gly Glu Ala Glu Lys Arg Leu

250 255 260

Leu Leu Val Asp Phe Ser Ser Gln Ala Leu Phe Gln Asp Lys Asn Ser

265 270 275

Ser Gln Val Leu Gly Glu Lys Val Leu Gly Ile Val Val Gln Asn Thr

280 285 290 295

Lys Val Ala Asn Leu Thr Glu Pro Val Val Leu Thr Phe Gln His Gln

300 305 310

Leu Gln Pro Lys Asn Val Thr Leu Gln Cys Val Phe Trp Val Glu Asp

315 320 325

Pro Thr Leu Ser Ser Pro Gly His Trp Ser Ser Ala Gly Cys Glu Thr

330 335 340

Val Arg Arg Glu Thr Gln Thr Ser Cys Phe Cys Asn His Leu Thr Tyr

345 350 355

Phe Ala Val Leu Met Val Ser Ser Val Glu Val Asp Ala Val His Lys

360 365 370 375

His Tyr Leu Ser Leu Leu Ser Tyr Val Gly Cys Val Val Ser Ala Leu

380 385 390

Ala Cys Leu Val Ser Ile Ala Ala Tyr Leu Cys Ser Arg Arg Lys Pro

395 400 405

Arg Asp Tyr Thr Ile Lys Val His Met Asn Leu Leu Leu Ala Val Phe

410 415 420

Leu Leu Asp Thr Ser Phe Leu Leu Ser Glu Pro Val Ala Leu Thr Gly

425 430 435

Ser Glu Ala Gly Cys Arg Ala Ser Ala Ile Phe Leu His Phe Ser Leu

440 445 450 455

Leu Thr Cys Leu Ser Trp Met Gly Leu Glu Gly Tyr Asn Leu Tyr Arg

460 465 470

Leu Val Val Glu Val Phe Gly Thr Tyr Val Pro Gly Tyr Leu Leu Lys

475 480 485

Leu Ser Ala Met Gly Trp Gly Phe Pro Ile Phe Leu Val Thr Leu Val

490 495 500

Ala Leu Val Asp Val Asp Asn Tyr Gly Pro Ile Ile Leu Ala Val His

505 510 515

Arg Thr Pro Glu Gly Val Ile Tyr Pro Ser Met Cys Trp Ile Arg Asp

520 525 530 535

Ser Leu Val Ser Tyr Ile Thr Asn Leu Gly Leu Phe Ser Leu Val Phe

540 545 550

Leu Phe Asn Met Ala Met Leu Ala Thr Met Val Val Gln Ile Leu Arg

555 560 565

Leu Arg Pro His Thr Gln Lys Trp Ser His Val Leu Thr Leu Leu Gly

570 575 580

Leu Ser Leu Val Leu Gly Leu Pro Trp Ala Leu Ile Phe Phe Ser Phe

585 590 595

Ala Ser Gly Thr Phe Gln Leu Val Val Leu Tyr Leu Phe Ser Ile Ile

600 605 610 615

Thr Ser Phe Gln Gly Phe Leu Ile Phe Ile Trp Tyr Trp Ser Met Arg

620 625 630

Leu Gln Ala Arg Gly Gly Pro Ser Pro Leu Lys Ser Asn Ser Asp Ser

635 640 645

Ala Arg Leu Pro Ile Ser Ser Gly Ser Thr Ser Ser Ser Arg Ile

650 655 660

<210> SEQ ID NO 74

<211> LENGTH: 2061

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 74

atgactcccc agtcgctgct gcagacgaca ctgttcctgc tgagtctgct cttcctggtc 60

caaggtgccc acggcagggg ccacagggaa gactttcgct tctgcagcca gcggaaccag 120

acacacagga gcagcctcca ctacaaaccc acaccagacc tgcgcatctc catcgagaac 180

tccgaagagg ccctcacagt ccatgcccct ttccctgcag cccaccctgc ttcccgatcc 240

ttccctgacc ccaggggcct ctaccacttc tgcctctact ggaaccgaca tgctgggaga 300

ttacatcttc tctatggcaa gcgtgacttc ttgctgagtg acaaagcctc tagcctcctc 360

tgcttccagc accaggagga gagcctggct cagggccccc cgctgttagc cacttctgtc 420

acctcctggt ggagccctca gaacatcagc ctgcccagtg ccgccagctt caccttctcc 480

ttccacagtc ctccccacac ggccgctcac aatgcctcgg tggacatgtg cgagctcaaa 540

agggacctcc agctgctcag ccagttcctg aagcatcccc agaaggcctc aaggaggccc 600

tcggctgccc ccgccagcca gcagttgcag agcctggagt cgaaactgac ctctgtgaga 660

ttcatggggg acatggtgtc cttcgaggag gaccggatca acgccacggt gtggaagctc 720

cagcccacag ccggcctcca ggacctgcac atccactccc ggcaggagga ggagcagagc 780

gagatcatgg agtactcggt gctgctgcct cgaacactct tccagaggac gaaaggccgg 840

aggggggagg ctgagaagag actcctcctg gtggacttca gcagccaagc cctgttccag 900

gacaagaatt ccagccaagt cctgggtgag aaggtcttgg ggattgtggt acagaacacc 960

aaagtagcca acctcacgga gcccgtggtg ctcaccttcc agcaccagct acagccgaag 1020

aatgtgactc tgcaatgtgt gttctgggtt gaagacccca cattgagcag cccggggcat 1080

tggagcagtg ctgggtgtga gaccgtcagg agagaaaccc aaacatcctg cttctgcaac 1140

cacttgacct actttgcagt gctgatggtc tcctcggtgg aggtggacgc cgtgcacaag 1200

cactacctga gcctcctctc ctacgtgggc tgtgtcgtct ctgccctggc ctgccttgtc 1260

agcattgccg cctacctctg ctccaggagg aaacctcggg actacaccat caaggtgcac 1320

atgaacctgc tgctggccgt cttcctgctg gacacgagct tcctgctcag cgagccggtg 1380

gccctgacag gctctgaggc tggctgccga gccagtgcca tcttcctgca cttctccctg 1440

ctcacctgcc tttcctggat gggcctcgag gggtacaacc tctaccgact cgtggtggag 1500

gtctttggca cctatgtccc tggctaccta ctcaagctga gcgccatggg ctggggcttc 1560

cccatctttc tggtgacgct ggtggccctg gtggatgtgg acaactatgg ccccatcatc 1620

ttggctgtgc ataggactcc agagggcgtc atctaccctt ccatgtgctg gatccgggac 1680

tccctggtca gctacatcac caacctgggc ctcttcagcc tggtgtttct gttcaacatg 1740

gccatgctag ccaccatggt ggtgcagatc ctgcggctgc gcccccacac ccaaaagtgg 1800

tcacatgtgc tgacactgct gggcctcagc ctggtccttg gcctgccctg ggccttgatc 1860

ttcttctcct ttgcttctgg caccttccag cttgtcgtcc tctacctttt cagcatcatc 1920

acctccttcc aaggcttcct catcttcatc tggtactggt ccatgcggct gcaggcccgg 1980

ggtggcccct cccctctgaa gagcaactca gacagcgcca ggctccccat cagctcgggc 2040

agcacctcgt ccagccgcat c 2061

<210> SEQ ID NO 75

<211> LENGTH: 3564

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<220> FEATURE:

<221> NAME/KEY: sig_peptide

<222> LOCATION: (43)..(2103)

<221> NAME/KEY: mat_peptide

<222> LOCATION: (118)..(2103)

<221> NAME/KEY: CDS

<222> LOCATION: (43)..(2103)

<400> SEQUENCE: 75

attacaggtg gtgacttcca agagtgactc cgtcggagga aa atg act ccc cag 54

Met Thr Pro Gln

-25

tcg ctg ctg cag acg aca ctg ttc ctg ctg agt ctg ctc ttc ctg gtc 102

Ser Leu Leu Gln Thr Thr Leu Phe Leu Leu Ser Leu Leu Phe Leu Val

-20 -15 -10

caa ggt gcc cac ggc agg ggc cac agg gaa gac ttt cgc ttc tgc agc 150

Gln Gly Ala His Gly Arg Gly His Arg Glu Asp Phe Arg Phe Cys Ser

-5 -1 1 5 10

cag cgg aac cag aca cac agg agc agc ctc cac tac aaa ccc aca cca 198

Gln Arg Asn Gln Thr His Arg Ser Ser Leu His Tyr Lys Pro Thr Pro

15 20 25

gac ctg cgc atc tcc atc gag aac tcc gaa gag gcc ctc aca gtc cat 246

Asp Leu Arg Ile Ser Ile Glu Asn Ser Glu Glu Ala Leu Thr Val His

30 35 40

gcc cct ttc cct gca gcc cac cct gct tcc cga tcc ttc cct gac ccc 294

Ala Pro Phe Pro Ala Ala His Pro Ala Ser Arg Ser Phe Pro Asp Pro

45 50 55

agg ggc ctc tac cac ttc tgc ctc tac tgg aac cga cat gct ggg aga 342

Arg Gly Leu Tyr His Phe Cys Leu Tyr Trp Asn Arg His Ala Gly Arg

60 65 70 75

tta cat ctt ctc tat ggc aag cgt gac ttc ttg ctg agt gac aaa gcc 390

Leu His Leu Leu Tyr Gly Lys Arg Asp Phe Leu Leu Ser Asp Lys Ala

80 85 90

tct agc ctc ctc tgc ttc cag cac cag gag gag agc ctg gct cag ggc 438

Ser Ser Leu Leu Cys Phe Gln His Gln Glu Glu Ser Leu Ala Gln Gly

95 100 105

ccc ccg ctg tta gcc act tct gtc acc tcc tgg tgg agc cct cag aac 486

Pro Pro Leu Leu Ala Thr Ser Val Thr Ser Trp Trp Ser Pro Gln Asn

110 115 120

atc agc ctg ccc agt gcc gcc agc ttc acc ttc tcc ttc cac agt cct 534

Ile Ser Leu Pro Ser Ala Ala Ser Phe Thr Phe Ser Phe His Ser Pro

125 130 135

ccc cac acg gcc gct cac aat gcc tcg gtg gac atg tgc gag ctc aaa 582

Pro His Thr Ala Ala His Asn Ala Ser Val Asp Met Cys Glu Leu Lys

140 145 150 155

agg gac ctc cag ctg ctc agc cag ttc ctg aag cat ccc cag aag gcc 630

Arg Asp Leu Gln Leu Leu Ser Gln Phe Leu Lys His Pro Gln Lys Ala

160 165 170

tca agg agg ccc tcg gct gcc ccc gcc agc cag cag ttg cag agc ctg 678

Ser Arg Arg Pro Ser Ala Ala Pro Ala Ser Gln Gln Leu Gln Ser Leu

175 180 185

gag tcg aaa ctg acc tct gtg aga ttc atg ggg gac atg gtg tcc ttc 726

Glu Ser Lys Leu Thr Ser Val Arg Phe Met Gly Asp Met Val Ser Phe

190 195 200

gag gag gac cgg atc aac gcc acg gtg tgg aag ctc cag ccc aca gcc 774

Glu Glu Asp Arg Ile Asn Ala Thr Val Trp Lys Leu Gln Pro Thr Ala

205 210 215

ggc ctc cag gac ctg cac atc cac tcc cgg cag gag gag gag cag agc 822

Gly Leu Gln Asp Leu His Ile His Ser Arg Gln Glu Glu Glu Gln Ser

220 225 230 235

gag atc atg gag tac tcg gtg ctg ctg cct cga aca ctc ttc cag agg 870

Glu Ile Met Glu Tyr Ser Val Leu Leu Pro Arg Thr Leu Phe Gln Arg

240 245 250

acg aaa ggc cgg agg ggg gag gct gag aag aga ctc ctc ctg gtg gac 918

Thr Lys Gly Arg Arg Gly Glu Ala Glu Lys Arg Leu Leu Leu Val Asp

255 260 265

ttc agc agc caa gcc ctg ttc cag gac aag aat tcc agc caa gtc ctg 966

Phe Ser Ser Gln Ala Leu Phe Gln Asp Lys Asn Ser Ser Gln Val Leu

270 275 280

ggt gag aag gtc ttg ggg att gtg gta cag aac acc aaa gta gcc aac 1014

Gly Glu Lys Val Leu Gly Ile Val Val Gln Asn Thr Lys Val Ala Asn

285 290 295

ctc acg gag ccc gtg gtg ctc acc ttc cag cac cag cta cag ccg aag 1062

Leu Thr Glu Pro Val Val Leu Thr Phe Gln His Gln Leu Gln Pro Lys

300 305 310 315

aat gtg act ctg caa tgt gtg ttc tgg gtt gaa gac ccc aca ttg agc 1110

Asn Val Thr Leu Gln Cys Val Phe Trp Val Glu Asp Pro Thr Leu Ser

320 325 330

agc ccg ggg cat tgg agc agt gct ggg tgt gag acc gtc agg aga gaa 1158

Ser Pro Gly His Trp Ser Ser Ala Gly Cys Glu Thr Val Arg Arg Glu

335 340 345

acc caa aca tcc tgc ttc tgc aac cac ttg acc tac ttt gca gtg ctg 1206

Thr Gln Thr Ser Cys Phe Cys Asn His Leu Thr Tyr Phe Ala Val Leu

350 355 360

atg gtc tcc tcg gtg gag gtg gac gcc gtg cac aag cac tac ctg agc 1254

Met Val Ser Ser Val Glu Val Asp Ala Val His Lys His Tyr Leu Ser

365 370 375

ctc ctc tcc tac gtg ggc tgt gtc gtc tct gcc ctg gcc tgc ctt gtc 1302

Leu Leu Ser Tyr Val Gly Cys Val Val Ser Ala Leu Ala Cys Leu Val

380 385 390 395

agc att gcc gcc tac ctc tgc tcc agg agg aaa cct cgg gac tac acc 1350

Ser Ile Ala Ala Tyr Leu Cys Ser Arg Arg Lys Pro Arg Asp Tyr Thr

400 405 410

atc aag gtg cac atg aac ctg ctg ctg gcc gtc ttc ctg ctg gac acg 1398

Ile Lys Val His Met Asn Leu Leu Leu Ala Val Phe Leu Leu Asp Thr

415 420 425

agc ttc ctg ctc agc gag ccg gtg gcc ctg aca ggc tct gag gct ggc 1446

Ser Phe Leu Leu Ser Glu Pro Val Ala Leu Thr Gly Ser Glu Ala Gly

430 435 440

tgc cga gcc agt gcc atc ttc ctg cac ttc tcc ctg ctc acc tgc ctt 1494

Cys Arg Ala Ser Ala Ile Phe Leu His Phe Ser Leu Leu Thr Cys Leu

445 450 455

tcc tgg atg ggc ctc gag ggg tac aac ctc tac cga ctc gtg gtg gag 1542

Ser Trp Met Gly Leu Glu Gly Tyr Asn Leu Tyr Arg Leu Val Val Glu

460 465 470 475

gtc ttt ggc acc tat gtc cct ggc tac cta ctc aag ctg agc gcc atg 1590

Val Phe Gly Thr Tyr Val Pro Gly Tyr Leu Leu Lys Leu Ser Ala Met

480 485 490

ggc tgg ggc ttc ccc atc ttt ctg gtg acg ctg gtg gcc ctg gtg gat 1638

Gly Trp Gly Phe Pro Ile Phe Leu Val Thr Leu Val Ala Leu Val Asp

495 500 505

gtg gac aac tat ggc ccc atc atc ttg gct gtg cat agg act cca gag 1686

Val Asp Asn Tyr Gly Pro Ile Ile Leu Ala Val His Arg Thr Pro Glu

510 515 520

ggc gtc atc tac cct tcc atg tgc tgg atc cgg gac tcc ctg gtc agc 1734

Gly Val Ile Tyr Pro Ser Met Cys Trp Ile Arg Asp Ser Leu Val Ser

525 530 535

tac atc acc aac ctg ggc ctc ttc agc ctg gtg ttt ctg ttc aac atg 1782

Tyr Ile Thr Asn Leu Gly Leu Phe Ser Leu Val Phe Leu Phe Asn Met

540 545 550 555

gcc atg cta gcc acc atg gtg gtg cag atc ctg cgg ctg cgc ccc cac 1830

Ala Met Leu Ala Thr Met Val Val Gln Ile Leu Arg Leu Arg Pro His

560 565 570

acc caa aag tgg tca cat gtg ctg aca ctg ctg ggc ctc agc ctg gtc 1878

Thr Gln Lys Trp Ser His Val Leu Thr Leu Leu Gly Leu Ser Leu Val

575 580 585

ctt ggc ctg ccc tgg gcc ttg atc ttc ttc tcc ttt gct tct ggc acc 1926

Leu Gly Leu Pro Trp Ala Leu Ile Phe Phe Ser Phe Ala Ser Gly Thr

590 595 600

ttc cag ctt gtc gtc ctc tac ctt ttc agc atc atc acc tcc ttc caa 1974

Phe Gln Leu Val Val Leu Tyr Leu Phe Ser Ile Ile Thr Ser Phe Gln

605 610 615

ggc ttc ctc atc ttc atc tgg tac tgg tcc atg cgg ctg cag gcc cgg 2022

Gly Phe Leu Ile Phe Ile Trp Tyr Trp Ser Met Arg Leu Gln Ala Arg

620 625 630 635

ggt ggc ccc tcc cct ctg aag agc aac tca gac agc gcc agg ctc ccc 2070

Gly Gly Pro Ser Pro Leu Lys Ser Asn Ser Asp Ser Ala Arg Leu Pro

640 645 650

atc agc tcg ggc agc acc tcg tcc agc cgc atc taggcctcca gcccacctgc 2123

Ile Ser Ser Gly Ser Thr Ser Ser Ser Arg Ile

655 660

ccatgtgatg aagcagagat gcggcctcgt cgcacactgc ctgtggcccc cgagccaggc 2183

ccagccccag gccagtcagc cgcagacttt ggaaagccca acgaccatgg agagatgggc 2243

cgttgccatg gtggacggac tcccgggctg ggcttttgaa ttggccttgg ggactactcg 2303

gctctcactc agctcccacg ggactcagaa gtgcgccgcc atgctgccta gggtactgtc 2363

cccacatctg tcccaaccca gctggaggcc tggtctctcc ttacaacccc tgggcccagc 2423

cctcattgct gggggccagg ccttggatct tgagggtctg gcacatcctt aatcctgtgc 2483

ccctgcctgg gacagaaatg tggctccagt tgctctgtct ctcgtggtca ccctgagggc 2543

actctgcatc ctctgtcatt ttaacctcag gtggcaccca gggcgaatgg ggcccagggc 2603

agaccttcag ggccagagcc ctggcggagg agaggccctt tgccaggagc acagcagcag 2663

ctcgcctacc tctgagccca ggccccctcc ctccctcagc cccccagtcc tccctccatc 2723

ttccctgggg ttctcctcct ctcccagggc ctccttgctc cttcgttcac agctgggggt 2783

ccccgattcc aatgctgttt tttggggagt ggtttccagg agctgcctgg tgtctgctgt 2843

aaatgtttgt ctactgcaca agcctcggcc tgcccctgag ccaggctcgg taccgatgcg 2903

tgggctgggc taggtccctc tgtccatctg ggcctttgta tgagctgcat tgcccttgct 2963

caccctgacc aagcacacgc ctcagagggg ccctcagcct ctcctgaagc cctcttgtgg 3023

caagaactgt ggaccatgcc agtcccgtct ggtttccatc ccaccactcc aaggactgag 3083

actgacctcc tctggtgaca ctggcctaga gcctgacact ctcctaagag gttctctcca 3143

agcccccaaa tagctccagg cgccctcggc cgcccatcat ggttaattct gtccaacaaa 3203

cacacacggg tagattgctg gcctgttgta ggtggtaggg acacagatga ccgacctggt 3263

cactcctcct gccaacattc agtctggtat gtgaggcgtg cgtgaagcaa gaactcctgg 3323

agctacaggg acagggagcc atcattcctg cctgggaatc ctggaagact tcctgcagga 3383

gtcagcgttc aatcttgacc ttgaagatgg gaaggatgtt ctttttacgt accaattctt 3443

ttgtcttttg atattaaaaa gaagtacatg ttcattgtag agaatttgga aactgtagaa 3503

gagaatcaag aagaaaaata aaaatcagct gttgtaatcg cctagcaaaa aaaaaaaaaa 3563

a 3564

<210> SEQ ID NO 76

<211> LENGTH: 704

<212> TYPE: PRT

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 76

Met Phe Thr Phe Leu Leu Thr Cys Ile Phe Leu Pro Leu Leu Arg Gly

-15 -10 -5 -1

His Ser Leu Phe Thr Cys Glu Pro Ile Thr Val Pro Arg Cys Met Lys

1 5 10 15

Met Ala Tyr Asn Met Thr Phe Phe Pro Asn Leu Met Gly His Tyr Asp

20 25 30

Gln Ser Ile Ala Ala Val Glu Met Glu His Phe Leu Pro Leu Ala Asn

35 40 45

Leu Glu Cys Ser Pro Asn Ile Glu Thr Phe Leu Cys Lys Ala Phe Val

50 55 60

Pro Thr Cys Ile Glu Gln Ile His Val Val Pro Pro Cys Arg Lys Leu

65 70 75 80

Cys Glu Lys Val Tyr Ser Asp Cys Lys Lys Leu Ile Asp Thr Phe Gly

85 90 95

Ile Arg Trp Pro Glu Glu Leu Glu Cys Asp Arg Leu Gln Tyr Cys Asp

100 105 110

Glu Thr Val Pro Val Thr Phe Asp Pro His Thr Glu Phe Leu Gly Pro

115 120 125

Gln Lys Lys Thr Glu Gln Val Gln Arg Asp Ile Gly Phe Trp Cys Pro

130 135 140

Arg His Leu Lys Thr Ser Gly Gly Gln Gly Tyr Lys Phe Leu Gly Ile

145 150 155 160

Asp Gln Cys Ala Pro Pro Cys Pro Asn Met Tyr Phe Lys Ser Asp Glu

165 170 175

Leu Glu Phe Ala Lys Ser Phe Ile Gly Thr Val Ser Ile Phe Cys Leu

180 185 190

Cys Ala Thr Leu Phe Thr Phe Leu Thr Phe Leu Ile Asp Val Arg Arg

195 200 205

Phe Arg Tyr Pro Glu Arg Pro Ile Ile Tyr Tyr Ser Val Cys Tyr Ser

210 215 220

Ile Val Ser Leu Met Tyr Phe Ile Gly Phe Leu Leu Gly Asp Ser Thr

225 230 235 240

Ala Cys Asn Lys Ala Asp Glu Lys Leu Glu Leu Gly Asn Thr Val Val

245 250 255

Leu Asp Ser Gln Asn Lys Ala Cys Thr Val Leu Phe Met Leu Leu Tyr

260 265 270

Phe Phe Thr Met Ala Gly Thr Val Trp Trp Val Ile Leu Thr Ile Thr

275 280 285

Trp Phe Leu Ala Ala Gly Arg Lys Trp Ser Cys Glu Ala Ile Glu Gln

290 295 300

Lys Ala Val Trp Phe His Ala Val Ala Trp Gly Thr Pro Gly Phe Leu

305 310 315 320

Thr Val Met Leu Leu Ala Met Asn Lys Val Glu Gly Asp Asn Ile Ser

325 330 335

Gly Val Cys Phe Val Gly Leu Tyr Asp Leu Asp Ala Ser Arg Tyr Phe

340 345 350

Val Leu Leu Pro Leu Cys Leu Cys Val Phe Val Gly Leu Ser Leu Leu

355 360 365

Leu Ala Gly Ile Ile Ser Leu Asn His Val Arg Gln Val Ile Gln His

370 375 380

Asp Gly Arg Asn Gln Glu Lys Leu Lys Lys Phe Met Ile Arg Ile Gly

385 390 395 400

Val Phe Ser Gly Leu Tyr Leu Val Pro Leu Val Thr Leu Leu Gly Cys

405 410 415

Tyr Val Tyr Glu Gln Val Asn Arg Ile Thr Trp Glu Ile Thr Trp Val

420 425 430

Ser Asp His Cys Arg Gln Tyr His Ile Pro Cys Pro Tyr Gln Ala Lys

435 440 445

Ala Lys Ala Arg Pro Glu Leu Ala Leu Phe Met Ile Lys Tyr Leu Met

450 455 460

Thr Leu Ile Val Gly Ile Ser Ala Val Phe Trp Val Gly Ser Lys Lys

465 470 475 480

Thr Cys Thr Glu Trp Ala Gly Phe Phe Lys Arg Asn Arg Lys Arg Asp

485 490 495

Pro Ile Ser Glu Ser Arg Arg Val Leu Gln Glu Ser Cys Glu Phe Phe

500 505 510

Leu Lys His Asn Ser Lys Val Lys His Lys Lys Lys His Tyr Lys Pro

515 520 525

Ser Ser His Lys Leu Lys Val Ile Ser Lys Ser Met Gly Thr Ser Thr

530 535 540

Gly Ala Thr Ala Asn His Gly Thr Ser Ala Val Ala Ile Thr Ser His

545 550 555 560

Asp Tyr Leu Gly Gln Glu Thr Leu Thr Glu Ile Gln Thr Ser Pro Glu

565 570 575

Thr Ser Met Arg Glu Val Lys Ala Asp Gly Ala Ser Thr Pro Arg Leu

580 585 590

Arg Glu Gln Asp Cys Gly Glu Pro Ala Ser Pro Ala Ala Ser Ile Ser

595 600 605

Arg Leu Ser Gly Glu Gln Val Asp Gly Lys Gly Gln Ala Gly Ser Val

610 615 620

Ser Glu Ser Ala Arg Ser Glu Gly Arg Ile Ser Pro Lys Ser Asp Ile

625 630 635 640

Thr Asp Thr Gly Leu Ala Gln Ser Asn Asn Leu Gln Val Pro Ser Ser

645 650 655

Ser Glu Pro Ser Ser Leu Lys Gly Ser Thr Ser Leu Leu Val His Pro

660 665 670

Val Ser Gly Val Arg Lys Glu Gln Gly Gly Gly Cys His Ser Asp Thr

675 680 685

<210> SEQ ID NO 77

<211> LENGTH: 2112

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 77

atgtttacat ttttgttgac gtgtattttt ctacccctcc taagagggca cagtctcttc 60

acctgtgaac caattactgt tcccagatgt atgaaaatgg cctacaacat gacgtttttc 120

cctaatctga tgggtcatta tgaccagagt attgccgcgg tggaaatgga gcattttctt 180

cctctcgcaa atctggaatg ttcaccaaac attgaaactt tcctctgcaa agcatttgta 240

ccaacctgca tagaacaaat tcatgtggtt ccaccttgtc gtaaactttg tgagaaagta 300

tattctgatt gcaaaaaatt aattgacact tttgggatcc gatggcctga ggagcttgaa 360

tgtgacagat tacaatactg tgatgagact gttcctgtaa cttttgatcc acacacagaa 420

tttcttggtc ctcagaagaa aacagaacaa gtccaaagag acattggatt ttggtgtcca 480

aggcatctta agacttctgg gggacaagga tataagtttc tgggaattga ccagtgtgcg 540

cctccatgcc ccaacatgta ttttaaaagt gatgagctag agtttgcaaa aagttttatt 600

ggaacagttt caatattttg tctttgtgca actctgttca cattccttac ttttttaatt 660

gatgttagaa gattcagata cccagagaga ccaattatat attactctgt ctgttacagc 720

attgtatctc ttatgtactt cattggattt ttgctaggcg atagcacagc ctgcaataag 780

gcagatgaga agctagaact tggtaacact gttgtcctag actctcaaaa taaggcttgc 840

accgttttgt tcatgctttt gtattttttc acaatggctg gcactgtgtg gtgggtgatt 900

cttaccatta cttggttctt agctgcagga agaaaatgga gttgtgaagc catcgagcaa 960

aaagcagtgt ggtttcatgc tgttgcatgg ggaacaccag gtttcctgac tgttatgctt 1020

cttgctatga acaaagttga aggagacaac attagtggag tttgctttgt tggcctttat 1080

gacctggatg cttctcgcta ctttgtactc ttgccactgt gcctttgtgt gtttgttggg 1140

ctctctcttc ttttagctgg cattatttcc ttaaatcatg ttcgacaagt catacaacat 1200

gatggccgga accaagaaaa actaaagaaa tttatgattc gaattggagt cttcagcggc 1260

ttgtatcttg tgccattagt gacacttctc ggatgttacg tctatgagca agtgaacagg 1320

attacctggg agataacttg ggtctctgat cattgtcgtc agtaccatat cccatgtcct 1380

tatcaggcaa aagcaaaagc tcgaccagaa ttggctttat ttatgataaa atacctgatg 1440

acattaattg ttggcatctc tgctgtcttc tgggttggaa gcaaaaagac atgcacagaa 1500

tgggctgggt tttttaaacg aaatcgcaag agagatccaa tcagtgaaag tcgaagagta 1560

ctacaggaat catgtgagtt tttcttaaag cacaattcta aagttaaaca caaaaagaag 1620

cactataaac caagttcaca caagctgaag gtcatttcca aatccatggg aaccagcaca 1680

ggagctacag caaatcatgg cacttctgca gtagcaatta ctagccatga ttacctagga 1740

caagaaactt tgacagaaat ccaaacctca ccagaaacat caatgagaga ggtgaaagcg 1800

gacggagcta gcacccccag gttaagagaa caggactgtg gtgaacctgc ctcgccagca 1860

gcatccatct ccagactctc tggggaacag gtcgacggga agggccaggc aggcagtgta 1920

tctgaaagtg cgcggagtga aggaaggatt agtccaaaga gtgatattac tgacactggc 1980

ctggcacaga gcaacaattt gcaggtcccc agttcttcag aaccaagcag cctcaaaggt 2040

tccacatctc tgcttgttca cccggtttca ggagtgagaa aagagcaggg aggtggttgt 2100

cattcagata ct 2112

<210> SEQ ID NO 78

<211> LENGTH: 3492

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<220> FEATURE:

<221> NAME/KEY: sig_peptide

<222> LOCATION: (6)..(53)

<221> NAME/KEY: mat_peptide

<222> LOCATION: (54)..(2117)

<221> NAME/KEY: CDS

<222> LOCATION: (6)..(2117)

<400> SEQUENCE: 78

tggaa atg ttt aca ttt ttg ttg acg tgt att ttt cta ccc ctc cta aga 50

Met Phe Thr Phe Leu Leu Thr Cys Ile Phe Leu Pro Leu Leu Arg

-15 -10 -5

ggg cac agt ctc ttc acc tgt gaa cca att act gtt ccc aga tgt atg 98

Gly His Ser Leu Phe Thr Cys Glu Pro Ile Thr Val Pro Arg Cys Met

-1 1 5 10 15

aaa atg gcc tac aac atg acg ttt ttc cct aat ctg atg ggt cat tat 146

Lys Met Ala Tyr Asn Met Thr Phe Phe Pro Asn Leu Met Gly His Tyr

20 25 30

gac cag agt att gcc gcg gtg gaa atg gag cat ttt ctt cct ctc gca 194

Asp Gln Ser Ile Ala Ala Val Glu Met Glu His Phe Leu Pro Leu Ala

35 40 45

aat ctg gaa tgt tca cca aac att gaa act ttc ctc tgc aaa gca ttt 242

Asn Leu Glu Cys Ser Pro Asn Ile Glu Thr Phe Leu Cys Lys Ala Phe

50 55 60

gta cca acc tgc ata gaa caa att cat gtg gtt cca cct tgt cgt aaa 290

Val Pro Thr Cys Ile Glu Gln Ile His Val Val Pro Pro Cys Arg Lys

65 70 75

ctt tgt gag aaa gta tat tct gat tgc aaa aaa tta att gac act ttt 338

Leu Cys Glu Lys Val Tyr Ser Asp Cys Lys Lys Leu Ile Asp Thr Phe

80 85 90 95

ggg atc cga tgg cct gag gag ctt gaa tgt gac aga tta caa tac tgt 386

Gly Ile Arg Trp Pro Glu Glu Leu Glu Cys Asp Arg Leu Gln Tyr Cys

100 105 110

gat gag act gtt cct gta act ttt gat cca cac aca gaa ttt ctt ggt 434

Asp Glu Thr Val Pro Val Thr Phe Asp Pro His Thr Glu Phe Leu Gly

115 120 125

cct cag aag aaa aca gaa caa gtc caa aga gac att gga ttt tgg tgt 482

Pro Gln Lys Lys Thr Glu Gln Val Gln Arg Asp Ile Gly Phe Trp Cys

130 135 140

cca agg cat ctt aag act tct ggg gga caa gga tat aag ttt ctg gga 530

Pro Arg His Leu Lys Thr Ser Gly Gly Gln Gly Tyr Lys Phe Leu Gly

145 150 155

att gac cag tgt gcg cct cca tgc ccc aac atg tat ttt aaa agt gat 578

Ile Asp Gln Cys Ala Pro Pro Cys Pro Asn Met Tyr Phe Lys Ser Asp

160 165 170 175

gag cta gag ttt gca aaa agt ttt att gga aca gtt tca ata ttt tgt 626

Glu Leu Glu Phe Ala Lys Ser Phe Ile Gly Thr Val Ser Ile Phe Cys

180 185 190

ctt tgt gca act ctg ttc aca ttc ctt act ttt tta att gat gtt aga 674

Leu Cys Ala Thr Leu Phe Thr Phe Leu Thr Phe Leu Ile Asp Val Arg

195 200 205

aga ttc aga tac cca gag aga cca att ata tat tac tct gtc tgt tac 722

Arg Phe Arg Tyr Pro Glu Arg Pro Ile Ile Tyr Tyr Ser Val Cys Tyr

210 215 220

agc att gta tct ctt atg tac ttc att gga ttt ttg cta ggc gat agc 770

Ser Ile Val Ser Leu Met Tyr Phe Ile Gly Phe Leu Leu Gly Asp Ser

225 230 235

aca gcc tgc aat aag gca gat gag aag cta gaa ctt ggt aac act gtt 818

Thr Ala Cys Asn Lys Ala Asp Glu Lys Leu Glu Leu Gly Asn Thr Val

240 245 250 255

gtc cta gac tct caa aat aag gct tgc acc gtt ttg ttc atg ctt ttg 866

Val Leu Asp Ser Gln Asn Lys Ala Cys Thr Val Leu Phe Met Leu Leu

260 265 270

tat ttt ttc aca atg gct ggc act gtg tgg tgg gtg att ctt acc att 914

Tyr Phe Phe Thr Met Ala Gly Thr Val Trp Trp Val Ile Leu Thr Ile

275 280 285

act tgg ttc tta gct gca gga aga aaa tgg agt tgt gaa gcc atc gag 962

Thr Trp Phe Leu Ala Ala Gly Arg Lys Trp Ser Cys Glu Ala Ile Glu

290 295 300

caa aaa gca gtg tgg ttt cat gct gtt gca tgg gga aca cca ggt ttc 1010

Gln Lys Ala Val Trp Phe His Ala Val Ala Trp Gly Thr Pro Gly Phe

305 310 315

ctg act gtt atg ctt ctt gct atg aac aaa gtt gaa gga gac aac att 1058

Leu Thr Val Met Leu Leu Ala Met Asn Lys Val Glu Gly Asp Asn Ile

320 325 330 335

agt gga gtt tgc ttt gtt ggc ctt tat gac ctg gat gct tct cgc tac 1106

Ser Gly Val Cys Phe Val Gly Leu Tyr Asp Leu Asp Ala Ser Arg Tyr

340 345 350

ttt gta ctc ttg cca ctg tgc ctt tgt gtg ttt gtt ggg ctc tct ctt 1154

Phe Val Leu Leu Pro Leu Cys Leu Cys Val Phe Val Gly Leu Ser Leu

355 360 365

ctt tta gct ggc att att tcc tta aat cat gtt cga caa gtc ata caa 1202

Leu Leu Ala Gly Ile Ile Ser Leu Asn His Val Arg Gln Val Ile Gln

370 375 380

cat gat ggc cgg aac caa gaa aaa cta aag aaa ttt atg att cga att 1250

His Asp Gly Arg Asn Gln Glu Lys Leu Lys Lys Phe Met Ile Arg Ile

385 390 395

gga gtc ttc agc ggc ttg tat ctt gtg cca tta gtg aca ctt ctc gga 1298

Gly Val Phe Ser Gly Leu Tyr Leu Val Pro Leu Val Thr Leu Leu Gly

400 405 410 415

tgt tac gtc tat gag caa gtg aac agg att acc tgg gag ata act tgg 1346

Cys Tyr Val Tyr Glu Gln Val Asn Arg Ile Thr Trp Glu Ile Thr Trp

420 425 430

gtc tct gat cat tgt cgt cag tac cat atc cca tgt cct tat cag gca 1394

Val Ser Asp His Cys Arg Gln Tyr His Ile Pro Cys Pro Tyr Gln Ala

435 440 445

aaa gca aaa gct cga cca gaa ttg gct tta ttt atg ata aaa tac ctg 1442

Lys Ala Lys Ala Arg Pro Glu Leu Ala Leu Phe Met Ile Lys Tyr Leu

450 455 460

atg aca tta att gtt ggc atc tct gct gtc ttc tgg gtt gga agc aaa 1490

Met Thr Leu Ile Val Gly Ile Ser Ala Val Phe Trp Val Gly Ser Lys

465 470 475

aag aca tgc aca gaa tgg gct ggg ttt ttt aaa cga aat cgc aag aga 1538

Lys Thr Cys Thr Glu Trp Ala Gly Phe Phe Lys Arg Asn Arg Lys Arg

480 485 490 495

gat cca atc agt gaa agt cga aga gta cta cag gaa tca tgt gag ttt 1586

Asp Pro Ile Ser Glu Ser Arg Arg Val Leu Gln Glu Ser Cys Glu Phe

500 505 510

ttc tta aag cac aat tct aaa gtt aaa cac aaa aag aag cac tat aaa 1634

Phe Leu Lys His Asn Ser Lys Val Lys His Lys Lys Lys His Tyr Lys

515 520 525

cca agt tca cac aag ctg aag gtc att tcc aaa tcc atg gga acc agc 1682

Pro Ser Ser His Lys Leu Lys Val Ile Ser Lys Ser Met Gly Thr Ser

530 535 540

aca gga gct aca gca aat cat ggc act tct gca gta gca att act agc 1730

Thr Gly Ala Thr Ala Asn His Gly Thr Ser Ala Val Ala Ile Thr Ser

545 550 555

cat gat tac cta gga caa gaa act ttg aca gaa atc caa acc tca cca 1778

His Asp Tyr Leu Gly Gln Glu Thr Leu Thr Glu Ile Gln Thr Ser Pro

560 565 570 575

gaa aca tca atg aga gag gtg aaa gcg gac gga gct agc acc ccc agg 1826

Glu Thr Ser Met Arg Glu Val Lys Ala Asp Gly Ala Ser Thr Pro Arg

580 585 590

tta aga gaa cag gac tgt ggt gaa cct gcc tcg cca gca gca tcc atc 1874

Leu Arg Glu Gln Asp Cys Gly Glu Pro Ala Ser Pro Ala Ala Ser Ile

595 600 605

tcc aga ctc tct ggg gaa cag gtc gac ggg aag ggc cag gca ggc agt 1922

Ser Arg Leu Ser Gly Glu Gln Val Asp Gly Lys Gly Gln Ala Gly Ser

610 615 620

gta tct gaa agt gcg cgg agt gaa gga agg att agt cca aag agt gat 1970

Val Ser Glu Ser Ala Arg Ser Glu Gly Arg Ile Ser Pro Lys Ser Asp

625 630 635

att act gac act ggc ctg gca cag agc aac aat ttg cag gtc ccc agt 2018

Ile Thr Asp Thr Gly Leu Ala Gln Ser Asn Asn Leu Gln Val Pro Ser

640 645 650 655

tct tca gaa cca agc agc ctc aaa ggt tcc aca tct ctg ctt gtt cac 2066

Ser Ser Glu Pro Ser Ser Leu Lys Gly Ser Thr Ser Leu Leu Val His

660 665 670

ccg gtt tca gga gtg aga aaa gag cag gga ggt ggt tgt cat tca gat 2114

Pro Val Ser Gly Val Arg Lys Glu Gln Gly Gly Gly Cys His Ser Asp

675 680 685

act tgaagaacat tttctctcgt tactcagaag caaatttgtg ttacactgga 2167

Thr

agtgacctat gcactgtttt gtaagaatca ctgttacgtt cttcttttgc acttaaagtt 2227

gcattgccta ctgttatact ggaaaaaata gagttcaaga ataatatgac tcatttcaca 2287

caaaggttaa tgacaacaat atacctgaaa acagagatgt gcaggttaat aatatttttt 2347

taatagtgtg ggaggacaga gttagaggaa tcttcctttt ctatttatga agattctact 2407

cttggtaaga gtattttaag atgtactatg ctattttact tttttgatat aaaatcaaga 2467

tatttctttg ctgaagtatt taaatcttat ccttgtatct ttttatacat atttgaaaat 2527

aagcttatat gtatttgaac ttttttgaaa tcctattcaa gtatttttat catgctattg 2587

tgatatttta gcactttggt agcttttaca ctgaatttct aagaaaattg taaaatagtc 2647

ttcttttata ctgtaaaaaa agatatacca aaaagtctta taataggaat ttaactttaa 2707

aaacccactt attgatacct taccatctaa aatgtgtgat ttttatagtc tcgttttagg 2767

aatttcacag atctaaatta tgtagctgaa ataaggtgct tactcaaaga gtgtccacta 2827

ttgattgtat tatgctgctc actgatcctt ctgcatattt aaaataaaat gtcctaaagg 2887

gttagtagac aaaatgttag tcttttgtat attaggccaa gtgcaattga cttccctttt 2947

ttaatgtttc atgaccaccc attgattgta ttataaccac ttacagttgc ttatattttt 3007

tgttttaact tttgtttttt aacatttaga atattacatt ttgtattata cagtaccttt 3067

ctcagacatt ttgtagaatt catttcggca gctcactagg attttgctga acattaaaaa 3127

gtgtgatagc gatattagtg ccaatcaaat ggaaaaaagg tagtcttaat aaacaagaca 3187

caacgttttt atacaacata ctttaaaata ttaaggagtt ttcttaattt tgtttcctat 3247

taagtattat tctttgggca agattttctg atgcttttga ttttctctca atttagcatt 3307

tgcttttggt ttttttctct atttagcatt ctgttaaggc acaaaaacta tgtactgtat 3367

gggaaatgtt gtaaatatta ccttttccac attttaaaca gacaactttg aatacaaaaa 3427

ctttgttttg tgtgatcttt tcattaataa aattatcttt gtataagaaa aaaaaaaaaa 3487

aaaaa 3492

<210> SEQ ID NO 79

<211> LENGTH: 551

<212> TYPE: PRT

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 79

Met Leu Cys Ser Leu Leu Leu Cys Glu Cys Leu Leu Leu Val Ala Gly

-15 -10 -5

Tyr Ala His Asp Asp Asp Trp Ile Asp Pro Thr Asp Met Leu Asn Tyr

-1 1 5 10

Asp Ala Ala Ser Gly Thr Met Arg Lys Ser Gln Ala Lys Tyr Gly Ile

15 20 25 30

Ser Gly Glu Lys Asp Val Ser Pro Asp Leu Ser Cys Ala Asp Glu Ile

35 40 45

Ser Glu Cys Tyr His Lys Leu Asp Ser Leu Thr Tyr Lys Ile Asp Glu

50 55 60

Cys Glu Lys Lys Lys Arg Glu Asp Tyr Glu Ser Gln Ser Asn Pro Val

65 70 75

Phe Arg Arg Tyr Leu Asn Lys Ile Leu Ile Glu Ala Gly Lys Leu Gly

80 85 90

Leu Pro Asp Glu Asn Lys Gly Asp Met His Tyr Asp Ala Glu Ile Ile

95 100 105 110

Leu Lys Arg Glu Thr Leu Leu Glu Ile Gln Lys Phe Leu Asn Gly Glu

115 120 125

Asp Trp Lys Pro Gly Ala Leu Asp Asp Ala Leu Ser Asp Ile Leu Ile

130 135 140

Asn Phe Lys Phe His Asp Phe Glu Thr Trp Lys Trp Arg Phe Glu Asp

145 150 155

Ser Phe Gly Val Asp Pro Tyr Asn Val Leu Met Val Leu Leu Cys Leu

160 165 170

Leu Cys Ile Val Val Leu Val Ala Thr Glu Leu Trp Thr Tyr Val Arg

175 180 185 190

Trp Tyr Thr Gln Leu Arg Arg Val Leu Ile Ile Ser Phe Leu Phe Ser

195 200 205

Leu Gly Trp Asn Trp Met Tyr Leu Tyr Lys Leu Ala Phe Ala Gln His

210 215 220

Gln Ala Glu Val Ala Lys Met Glu Pro Leu Asn Asn Val Cys Ala Lys

225 230 235

Lys Met Asp Trp Thr Gly Ser Ile Trp Glu Trp Phe Arg Ser Ser Trp

240 245 250

Thr Tyr Lys Asp Asp Pro Cys Gln Lys Tyr Tyr Glu Leu Leu Leu Val

255 260 265 270

Asn Pro Ile Trp Leu Val Pro Pro Thr Lys Ala Leu Ala Val Thr Phe

275 280 285

Thr Thr Phe Val Thr Glu Pro Leu Lys His Ile Gly Lys Gly Thr Gly

290 295 300

Glu Phe Ile Lys Ala Leu Met Lys Glu Ile Pro Ala Leu Leu His Leu

305 310 315

Pro Val Leu Ile Ile Met Ala Leu Ala Ile Leu Ser Phe Cys Tyr Gly

320 325 330

Ala Gly Lys Ser Val His Val Leu Arg His Ile Gly Gly Pro Glu Ser

335 340 345 350

Glu Pro Pro Gln Ala Leu Arg Pro Arg Asp Arg Arg Arg Gln Glu Glu

355 360 365

Ile Asp Tyr Arg Pro Asp Gly Gly Ala Gly Asp Ala Asp Phe His Tyr

370 375 380

Arg Gly Gln Met Gly Pro Thr Glu Gln Gly Pro Tyr Ala Lys Thr Tyr

385 390 395

Glu Gly Arg Arg Glu Ile Leu Arg Glu Arg Asp Val Asp Leu Arg Phe

400 405 410

Gln Thr Gly Asn Lys Ser Pro Glu Val Leu Arg Ala Phe Asp Val Pro

415 420 425 430

Asp Ala Glu Ala Arg Glu His Pro Thr Val Val Pro Ser His Lys Ser

435 440 445

Pro Val Leu Asp Thr Lys Pro Lys Glu Thr Gly Gly Ile Leu Gly Glu

450 455 460

Gly Thr Pro Lys Glu Ser Ser Thr Glu Ser Ser Gln Ser Ala Lys Pro

465 470 475

Val Ser Gly Gln Asp Thr Ser Gly Asn Thr Glu Gly Ser Pro Ala Ala

480 485 490

Glu Lys Ala Gln Leu Lys Ser Glu Ala Ala Gly Ser Pro Asp Gln Gly

495 500 505 510

Ser Thr Tyr Ser Pro Ala Arg Gly Val Ala Gly Pro Arg Gly Gln Asp

515 520 525

Pro Val Ser Ser Pro Cys Gly

530

<210> SEQ ID NO 80

<211> LENGTH: 1653

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<400> SEQUENCE: 80

atgctgtgtt ctttgctcct ttgtgaatgt ctgttgctgg tagctggtta tgctcatgat 60

gatgactgga ttgaccccac agacatgctt aactatgatg ctgcttcagg aacaatgaga 120

aaatctcagg caaaatatgg tatttcaggg gaaaaggatg tcagtcctga cttgtcatgt 180

gctgatgaaa tatcagaatg ttatcacaaa cttgattctt taacttataa gattgatgag 240

tgtgaaaaga aaaagaggga agactatgaa agtcaaagca atcctgtttt taggagatac 300

ttaaataaga ttttaattga agctggaaag cttggacttc ctgatgaaaa caaaggcgat 360

atgcattatg atgctgagat tatccttaaa agagaaactt tgttagaaat acagaagttt 420

ctcaatggag aagactggaa accaggtgcc ttggatgatg cactaagtga tattttaatt 480

aattttaagt ttcatgattt tgaaacatgg aagtggcgat tcgaagattc ctttggagtg 540

gatccatata atgtgttaat ggtacttctt tgtctgctct gcatcgtggt tttagtggct 600

accgagctgt ggacatatgt acgttggtac actcagttga gacgtgtttt aatcatcagc 660

tttctgttca gtttgggatg gaattggatg tatttatata agctagcttt tgcacagcat 720

caggctgaag tcgccaagat ggagccatta aacaatgtgt gtgccaaaaa gatggactgg 780

actggaagta tctgggaatg gtttagaagt tcatggacct ataaggatga cccatgccaa 840

aaatactatg agctcttact agtcaaccct atttggttgg tcccaccaac aaaggcactt 900

gcagttacat tcaccacatt tgtaacggag ccattgaagc atattggaaa aggaactggg 960

gaatttatta aagcactcat gaaggaaatt ccagcgctgc ttcatcttcc agtgctgata 1020

attatggcat tagccatcct gagtttctgc tatggtgctg gaaaatcagt tcatgtgctg 1080

agacatatag gcggtcctga gagcgaacct ccccaggcac ttcggccacg ggatagaaga 1140

cggcaggagg aaattgatta tagacctgat ggtggagcag gtgatgccga tttccattat 1200

aggggccaaa tgggccccac tgagcaaggc ccttatgcca aaacgtatga gggtagaaga 1260

gagattttga gagagagaga tgttgacttg agatttcaga ctggcaacaa gagccctgaa 1320

gtgctccggg catttgatgt accagacgca gaggcacgag agcatcccac ggtggtaccc 1380

agtcataaat cacctgtttt ggatacaaag cccaaggaga caggtggaat cctgggggaa 1440

ggcacaccga aagaaagcag tactgaaagc agccagtcgg ccaagcctgt ctctggccaa 1500

gacacatcag ggaatacaga aggttcaccc gcagcggaaa aggcccagct caagtctgaa 1560

gccgcaggca gcccagacca aggcagcaca tacagccccg caagaggtgt ggctggacca 1620

cgtggacagg atccggtcag cagcccctgt ggc 1653

<210> SEQ ID NO 81

<211> LENGTH: 2000

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<220> FEATURE:

<221> NAME/KEY: sig_peptide

<222> LOCATION: (82)..(135)

<221> NAME/KEY: mat_peptide

<222> LOCATION: (136)..(1734)

<221> NAME/KEY: CDS

<222> LOCATION: (82)..(1734)

<400> SEQUENCE: 81

gcggcggcaa gctgtgcgac ctcttctgcg gccggcctgg gcaggtgtct tcctcgagag 60

gcaggcaggg gatcccggac g atg ctg tgt tct ttg ctc ctt tgt gaa tgt 111

Met Leu Cys Ser Leu Leu Leu Cys Glu Cys

-15 -10

ctg ttg ctg gta gct ggt tat gct cat gat gat gac tgg att gac ccc 159

Leu Leu Leu Val Ala Gly Tyr Ala His Asp Asp Asp Trp Ile Asp Pro

-5 -1 1 5

aca gac atg ctt aac tat gat gct gct tca gga aca atg aga aaa tct 207

Thr Asp Met Leu Asn Tyr Asp Ala Ala Ser Gly Thr Met Arg Lys Ser

10 15 20

cag gca aaa tat ggt att tca ggg gaa aag gat gtc agt cct gac ttg 255

Gln Ala Lys Tyr Gly Ile Ser Gly Glu Lys Asp Val Ser Pro Asp Leu

25 30 35 40

tca tgt gct gat gaa ata tca gaa tgt tat cac aaa ctt gat tct tta 303

Ser Cys Ala Asp Glu Ile Ser Glu Cys Tyr His Lys Leu Asp Ser Leu

45 50 55

act tat aag att gat gag tgt gaa aag aaa aag agg gaa gac tat gaa 351

Thr Tyr Lys Ile Asp Glu Cys Glu Lys Lys Lys Arg Glu Asp Tyr Glu

60 65 70

agt caa agc aat cct gtt ttt agg aga tac tta aat aag att tta att 399

Ser Gln Ser Asn Pro Val Phe Arg Arg Tyr Leu Asn Lys Ile Leu Ile

75 80 85

gaa gct gga aag ctt gga ctt cct gat gaa aac aaa ggc gat atg cat 447

Glu Ala Gly Lys Leu Gly Leu Pro Asp Glu Asn Lys Gly Asp Met His

90 95 100

tat gat gct gag att atc ctt aaa aga gaa act ttg tta gaa ata cag 495

Tyr Asp Ala Glu Ile Ile Leu Lys Arg Glu Thr Leu Leu Glu Ile Gln

105 110 115 120

aag ttt ctc aat gga gaa gac tgg aaa cca ggt gcc ttg gat gat gca 543

Lys Phe Leu Asn Gly Glu Asp Trp Lys Pro Gly Ala Leu Asp Asp Ala

125 130 135

cta agt gat att tta att aat ttt aag ttt cat gat ttt gaa aca tgg 591

Leu Ser Asp Ile Leu Ile Asn Phe Lys Phe His Asp Phe Glu Thr Trp

140 145 150

aag tgg cga ttc gaa gat tcc ttt gga gtg gat cca tat aat gtg tta 639

Lys Trp Arg Phe Glu Asp Ser Phe Gly Val Asp Pro Tyr Asn Val Leu

155 160 165

atg gta ctt ctt tgt ctg ctc tgc atc gtg gtt tta gtg gct acc gag 687

Met Val Leu Leu Cys Leu Leu Cys Ile Val Val Leu Val Ala Thr Glu

170 175 180

ctg tgg aca tat gta cgt tgg tac act cag ttg aga cgt gtt tta atc 735

Leu Trp Thr Tyr Val Arg Trp Tyr Thr Gln Leu Arg Arg Val Leu Ile

185 190 195 200

atc agc ttt ctg ttc agt ttg gga tgg aat tgg atg tat tta tat aag 783

Ile Ser Phe Leu Phe Ser Leu Gly Trp Asn Trp Met Tyr Leu Tyr Lys

205 210 215

cta gct ttt gca cag cat cag gct gaa gtc gcc aag atg gag cca tta 831

Leu Ala Phe Ala Gln His Gln Ala Glu Val Ala Lys Met Glu Pro Leu

220 225 230

aac aat gtg tgt gcc aaa aag atg gac tgg act gga agt atc tgg gaa 879

Asn Asn Val Cys Ala Lys Lys Met Asp Trp Thr Gly Ser Ile Trp Glu

235 240 245

tgg ttt aga agt tca tgg acc tat aag gat gac cca tgc caa aaa tac 927

Trp Phe Arg Ser Ser Trp Thr Tyr Lys Asp Asp Pro Cys Gln Lys Tyr

250 255 260

tat gag ctc tta cta gtc aac cct att tgg ttg gtc cca cca aca aag 975

Tyr Glu Leu Leu Leu Val Asn Pro Ile Trp Leu Val Pro Pro Thr Lys

265 270 275 280

gca ctt gca gtt aca ttc acc aca ttt gta acg gag cca ttg aag cat 1023

Ala Leu Ala Val Thr Phe Thr Thr Phe Val Thr Glu Pro Leu Lys His

285 290 295

att gga aaa gga act ggg gaa ttt att aaa gca ctc atg aag gaa att 1071

Ile Gly Lys Gly Thr Gly Glu Phe Ile Lys Ala Leu Met Lys Glu Ile

300 305 310

cca gcg ctg ctt cat ctt cca gtg ctg ata att atg gca tta gcc atc 1119

Pro Ala Leu Leu His Leu Pro Val Leu Ile Ile Met Ala Leu Ala Ile

315 320 325

ctg agt ttc tgc tat ggt gct gga aaa tca gtt cat gtg ctg aga cat 1167

Leu Ser Phe Cys Tyr Gly Ala Gly Lys Ser Val His Val Leu Arg His

330 335 340

ata ggc ggt cct gag agc gaa cct ccc cag gca ctt cgg cca cgg gat 1215

Ile Gly Gly Pro Glu Ser Glu Pro Pro Gln Ala Leu Arg Pro Arg Asp

345 350 355 360

aga aga cgg cag gag gaa att gat tat aga cct gat ggt gga gca ggt 1263

Arg Arg Arg Gln Glu Glu Ile Asp Tyr Arg Pro Asp Gly Gly Ala Gly

365 370 375

gat gcc gat ttc cat tat agg ggc caa atg ggc ccc act gag caa ggc 1311

Asp Ala Asp Phe His Tyr Arg Gly Gln Met Gly Pro Thr Glu Gln Gly

380 385 390

cct tat gcc aaa acg tat gag ggt aga aga gag att ttg aga gag aga 1359

Pro Tyr Ala Lys Thr Tyr Glu Gly Arg Arg Glu Ile Leu Arg Glu Arg

395 400 405

gat gtt gac ttg aga ttt cag act ggc aac aag agc cct gaa gtg ctc 1407

Asp Val Asp Leu Arg Phe Gln Thr Gly Asn Lys Ser Pro Glu Val Leu

410 415 420

cgg gca ttt gat gta cca gac gca gag gca cga gag cat ccc acg gtg 1455

Arg Ala Phe Asp Val Pro Asp Ala Glu Ala Arg Glu His Pro Thr Val

425 430 435 440

gta ccc agt cat aaa tca cct gtt ttg gat aca aag ccc aag gag aca 1503

Val Pro Ser His Lys Ser Pro Val Leu Asp Thr Lys Pro Lys Glu Thr

445 450 455

ggt gga atc ctg ggg gaa ggc aca ccg aaa gaa agc agt act gaa agc 1551

Gly Gly Ile Leu Gly Glu Gly Thr Pro Lys Glu Ser Ser Thr Glu Ser

460 465 470

agc cag tcg gcc aag cct gtc tct ggc caa gac aca tca ggg aat aca 1599

Ser Gln Ser Ala Lys Pro Val Ser Gly Gln Asp Thr Ser Gly Asn Thr

475 480 485

gaa ggt tca ccc gca gcg gaa aag gcc cag ctc aag tct gaa gcc gca 1647

Glu Gly Ser Pro Ala Ala Glu Lys Ala Gln Leu Lys Ser Glu Ala Ala

490 495 500

ggc agc cca gac caa ggc agc aca tac agc ccc gca aga ggt gtg gct 1695

Gly Ser Pro Asp Gln Gly Ser Thr Tyr Ser Pro Ala Arg Gly Val Ala

505 510 515 520

gga cca cgt gga cag gat ccg gtc agc agc ccc tgt ggc tagaggaaca 1744

Gly Pro Arg Gly Gln Asp Pro Val Ser Ser Pro Cys Gly

525 530

ccagcacaaa cgacagcctc aagtctcctt cgagctttat atccatttgg ggatgaagtc 1804

tactttgaca gctagcaagg cgacatgcaa ctgttgttga atgatgacag caattcagga 1864

aagacttaaa tatgaaagca aattgaacac atcgggtgtt tgttatcaga aaagagatga 1924

gatgagataa gacttgttta ttgactagcc aatatgtcat taaaattaag gtttaaaaaa 1984

aaaaaaaaaa aaaaaa 2000

<210> SEQ ID NO 82

<211> LENGTH: 35

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Description of Artificial Sequence: XhoI-randam

9mer to synthesize doble strands cDNA

<221> NAME/KEY: modified_base

<222> LOCATION: (1)..(35)

<223> OTHER INFORMATION: “n” represents a, t, c, or g

<400> SEQUENCE: 82

cgattgaatt ctagacctgc ctcgagnnnn nnnnn 35

<210> SEQ ID NO 83

<211> LENGTH: 27

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Description of Artificial Sequence: biotin-

conjugated 0N056-F1 primer

<400> SEQUENCE: 83

aacatgaatc tttcgctcgt cctggct 27

<210> SEQ ID NO 84

<211> LENGTH: 28

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Description of Artificial Sequence: biotin-

conjugated 0N034-F1 primer

<400> SEQUENCE: 84

tgaagcccat cactacatcg ccattacg 28

<210> SEQ ID NO 85

<211> LENGTH: 27

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Description of Artificial Sequence: OX003-F1

primer

<400> SEQUENCE: 85

caaaacccac aagaaattca ccaaggc 27

<210> SEQ ID NO 86

<211> LENGTH: 23

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Description of Artificial Sequence: OX003-F2

primer

<400> SEQUENCE: 86

tcaccaaggc taacatggtg gcc 23

<210> SEQ ID NO 87

<211> LENGTH: 27

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Description of Artificial Sequence: OA052-F1

primer

<400> SEQUENCE: 87

atgcctagaa gaggactgat tcttcac 27

<210> SEQ ID NO 88

<211> LENGTH: 27

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Description of Artificial Sequence: OC004-F1

primer

<400> SEQUENCE: 88

atgaggaaag ggaaccttct gctgagc 27

<210> SEQ ID NO 89

<211> LENGTH: 18

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Description of Artificial Sequence: OC004-F2

primer

<400> SEQUENCE: 89

tgagcttcca gagctgtc 18

<210> SEQ ID NO 90

<211> LENGTH: 27

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Description of Artificial Sequence: OM017-F3

primer

<400> SEQUENCE: 90

gggaaatgaa acatttctgt aacctgc 27

<210> SEQ ID NO 91

<211> LENGTH: 27

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Description of Artificial Sequence: OM017-F1

primer

<400> SEQUENCE: 91

atgaaacatt tctgtaacct gctttgt 27

<210> SEQ ID NO 92

<211> LENGTH: 27

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Description of Artificial Sequence: OM101-F3

primer

<400> SEQUENCE: 92

tgaagttgca gataatgagg acttacc 27

<210> SEQ ID NO 93

<211> LENGTH: 27

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Description of Artificial Sequence: OM101-F1

primer

<400> SEQUENCE: 93

atgaggactt accattatat accatta 27

<210> SEQ ID NO 94

<211> LENGTH: 27

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Description of Artificial Sequence: OM126-F3

primer

<400> SEQUENCE: 94

aggaaggatg aggaagacca ggctctg 27

<210> SEQ ID NO 95

<211> LENGTH: 27

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Description of Artificial Sequence: biotin-

conjugated OM160-F1 primer

<400> SEQUENCE: 95

atgcttcagt ggaggagaag acactgc 27

<210> SEQ ID NO 96

<211> LENGTH: 27

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Description of Artificial Sequence: OMA016-F1

primer

<400> SEQUENCE: 96

agaaatggtg aatgcctgct ggtgtgg 27

<210> SEQ ID NO 97

<211> LENGTH: 27

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Description of Artificial Sequence: OMB130-F1

primer

<400> SEQUENCE: 97

tcctctgact tttcttctgc aagctcc 27

<210> SEQ ID NO 98

<211> LENGTH: 27

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Description of Artificial Sequence: OMB142-F2

primer

<400> SEQUENCE: 98

gcccaaggtc aaggagatgg tacggat 27

<210> SEQ ID NO 99

<211> LENGTH: 28

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Description of Artificial Sequence: OMB142-F1

primer

<400> SEQUENCE: 99

ggagatggta cggatcttaa ggactgtg 28

<210> SEQ ID NO 100

<211> LENGTH: 27

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Description of Artificial Sequence: OTB033-F1

primer

<400> SEQUENCE: 100

tgcactatcc aaaagctcca tgtacac 27

<210> SEQ ID NO 101

<211> LENGTH: 19

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Description of Artificial Sequence: OTB003-F2

primer

<400> SEQUENCE: 101

ccatgtacac agtgggggc 19

<210> SEQ ID NO 102

<211> LENGTH: 27

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Description of Artificial Sequence: OVB100-F1

primer

<400> SEQUENCE: 102

cacttggtgt ttgatttacc taagcac 27

<210> SEQ ID NO 103

<211> LENGTH: 27

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Description of Artificial Sequence: OAF062-F2

primer

<400> SEQUENCE: 103

gagtttcgta agcaaaatag aggacag 27

<210> SEQ ID NO 104

<211> LENGTH: 27

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Description of Artificial Sequence: OAF062-F3

primer

<400> SEQUENCE: 104

tagaggacag aaatgcagtt catgaac 27

<210> SEQ ID NO 105

<211> LENGTH: 28

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Description of Artificial Sequence: OAF075-F1

primer

<400> SEQUENCE: 105

gacatgaggt ggatactgtt cattgggg 28

<210> SEQ ID NO 106

<211> LENGTH: 28

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Description of Artificial Sequence: OAG119-F1

primer

<400> SEQUENCE: 106

tggcgtgtaa ctatgctcat cattgttc 28

<210> SEQ ID NO 107

<211> LENGTH: 28

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Description of Artificial Sequence: OAH040-F1

primer

<400> SEQUENCE: 107

ttagcccacc catgttgata gaacaccc 28

<210> SEQ ID NO 108

<211> LENGTH: 28

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Description of Artificial Sequence: OAH058-F1

primer

<400> SEQUENCE: 108

acaatgttgg cctgtctgca agcttgtg 28

<210> SEQ ID NO 109

<211> LENGTH: 27

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Description of Artificial Sequence: biotin-

conjugated OM011-F1 primer

<400> SEQUENCE: 109

gaagtgactc ttcctctagt ttgccac 27

<210> SEQ ID NO 110

<211> LENGTH: 27

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Description of Artificial Sequence: biotin-

conjugated OM028-F1 primer

<400> SEQUENCE: 110

atgaaggaca tgccactccg aattcat 27

<210> SEQ ID NO 111

<211> LENGTH: 27

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Description of Artificial Sequence: OMB092-F1

primer

<400> SEQUENCE: 111

actcacctgg atccctaagg gcacagc 27

<210> SEQ ID NO 112

<211> LENGTH: 28

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Description of Artificial Sequence: OMB092-F2

primer

<400> SEQUENCE: 112

agaatgagct attacggcag cagctatc 28

<210> SEQ ID NO 113

<211> LENGTH: 27

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Description of Artificial Sequence: OMB108-F1

primer

<400> SEQUENCE: 113

ctctctccat ctgctgtggt tatggcc 27

<210> SEQ ID NO 114

<211> LENGTH: 22

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Description of Artificial Sequence: OMB108-F2

primer

<400> SEQUENCE: 114

tggttatggc ctgtcgctgg ag 22

<210> SEQ ID NO 115

<211> LENGTH: 27

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Description of Artificial Sequence: biotin-

conjugated OT007-F1 primer

<400> SEQUENCE: 115

aaaatgactc cccagtcgct gctgcag 27

<210> SEQ ID NO 116

<211> LENGTH: 27

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Description of Artificial Sequence: OAG051-F1

primer

<400> SEQUENCE: 116

ggaaatgttt acatttttgt tgacgtg 27

<210> SEQ ID NO 117

<211> LENGTH: 27

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Description of Artificial Sequence: biotin-

conjugated OUB068-F1 primer

<400> SEQUENCE: 117

cactcatgaa ggaaattcca gcgctgc 27

Claims

1. A substantially purified form of the polypeptide comprising the amino acid sequence shown in SEQ ID NOS. 1, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40, 43, 46, 49, 52, 55, 58, 61, 64, 67, 70, 73, 76 or 79, homologue thereof, fragment thereof or homologue of the fragment.

2. A polypeptide according to claim 1 comprising the amino acid sequence shown in SEQ ID NOS. 1, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40, 43, 46, 49, 52, 55, 58, 61, 64, 67, 70, 73, 76 or 79.

3. A cDNA encoding the polypeptide according to claim 1.

4. A cDNA according to claim 3 comprising the nucleotide sequence shown in SEQ ID NOS. 2, 5, 8, 11, 14, 17, 20, 23, 26, 29, 32, 35, 38, 41, 44, 47, 50, 53, 56, 59, 62, 65, 68, 71, 74, 77 or 80, or a fragment cDNA selectively hybridized to the cDNA.

5. A cDNA according to claim 3 comprising the nucleotide sequence shown in SEQ ID NOS. 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78 or 81, or a fragment cDNA selectively hybridized to the cDNA.

6. A replication or expression vector carrying the cDNA according to claims 3 to 5.

7. A host cell transformed with the replication or expression vector according to claim 6.

8. A method for producing the polypeptide according to claim 1 or 2 which comprises culturing a host cell according to claim 7 under a condition effective to express the polypeptide according to claim 1 or 2.

9. A monoclonal or polyclonal antibody against the polypeptide according to claim 1 or 2.

10. A pharmaceutical composition containing the polypeptide according to claim 1 or 2 or the antibody according to claim 9, in association with pharmaceutically acceptable diluent and/or carrier.