KR20210128370A - Composition And Kit For Diagnosing Prognosis Of Bladder Cancer - Google Patents

Abstract

The present invention provides a composition for diagnosing the prognosis of bladder cancer, a kit for diagnosing the prognosis of bladder cancer comprising the same, and a method for providing the information necessary for diagnosing the prognosis of bladder cancer using the same. The composition for diagnosing the prognosis of bladder cancer and a kit for diagnosing the prognosis of bladder cancer comprising the same according to the present invention enable users to diagnose and predict the recurrence rate after treatment or the prognosis of a bladder cancer patient, and the like, thereby helping them to establish a treatment strategy for a bladder cancer patient.

Description

Composition and kit for prognosis diagnosis of bladder cancer {Composition And Kit For Diagnosing Prognosis Of Bladder Cancer}

The present invention relates to a composition for prognosis diagnosis of bladder cancer, a kit for prognosis diagnosis of bladder cancer comprising the same, and a method for providing information necessary for prognosis diagnosis of a bladder cancer patient using the same.

Bladder cancer (BC) is the most frequently occurring cancer in the urinary system. As such, the incidence rate is lower than in the West, but the incidence rate is increasing every year, and it is known as the cancer with the highest incidence among cancers of the urinary system in Korea (Lee C, et al., 1992).

Bladder cancer is largely divided into non-muscle invasive bladder cancer (NMIBC) and invasive (muscle invasive bladder cancer, MIBC) bladder cancer according to the degree of invasiveness. Noninvasive bladder cancer is a lesion in which the cancer is confined to the mucous membrane without invasion of the muscle layer. recurrence and progression to invasive cancer are problematic.

On the other hand, invasive bladder cancer refers to a state in which the cancer has penetrated to the muscle layer, and for its treatment, it is necessary to perform complex urinary diversion along with radical cystectomy, and it may lead to fatal results for the patient. Therefore, it is very important to predict, early detection and prevention of recurrence and progression after primary treatment.

For this reason, early diagnosis of bladder cancer and development of markers that can check the remaining lifespan after cancer onset is required. Patent Document 1 discloses a series of genetic markers that can be used for detection or diagnosis of human bladder cancer.

Although markers for diagnosing bladder cancer and other cancers have been developed, research has not yet been made on the relationship between the recurrence of bladder cancer patients or the survival rate of patients with recurrent bladder cancer and mutations in specific genes.

The present inventors focused on the need for the development of markers capable of diagnosing the recurrence of bladder cancer, or markers capable of diagnosing the prognosis of patients with recurrent bladder cancer, in order to determine a treatment strategy by discovering a therapeutic agent for patients with recurrent bladder cancer. , the relationship between survival or recurrence of bladder cancer and gene mutations found in bladder cancer patients, and the relationship between gene mutations and survival time in patients with recurrent bladder cancer were studied.

Korean Patent Publication No. 2014-0092905 (2014.07.24)

In order to apply a therapeutic strategy suitable for bladder cancer patients, it is necessary to develop a marker that can predict the prognosis of bladder cancer patients and provide information to determine a treatment strategy. An object of the present invention is to provide a marker that helps in diagnosing bladder cancer recurrence or prognosis in a patient, and determining a treatment strategy for a bladder cancer patient.

One aspect of the present invention is a mutation of the A2ML1 gene, ANAPC1 gene mutation, ARNT2 gene mutation, ASIC5 gene mutation, BIRC6 gene mutation, BTBD10 gene mutation, EDRF1 gene mutation, CFHR4 gene mutation, CLHC1 gene mutation , CTNND1 gene mutation, DCAF4 gene mutation, DHX37 gene mutation, EPAS1 gene mutation, FBN2 gene mutation, GLDC gene mutation, GRIA2 gene mutation, GUCY1A2 gene mutation, ITGA3 gene mutation, ITGA4 gene mutation , KIF19 gene mutation, KIF1B gene mutation, LPIN1 gene mutation, MAATS1 gene mutation, MCM8 gene mutation, MCTP1 gene mutation, MED1 gene mutation, MTUS2 gene mutation, NAV3 gene mutation, NME9 gene mutation , NOC3L gene mutation, NRXN3 gene mutation, PIK3C2A gene mutation, POLK gene mutation, PRKG2 gene mutation, RIN3 gene mutation, SCUBE2 gene mutation, SLC45A1 gene mutation, SORL1 gene mutation, SP4 gene mutation , TBC1D9 gene mutation, TEK gene mutation, TMC1 gene mutation, TNS3 gene mutation, TRPM3 gene mutation, TXK gene mutation, UNC13D gene mutation, ZNF207 gene mutation and ZNF282 gene mutation Provided is a composition for prognostic diagnosis of bladder cancer comprising a reagent capable of detecting a survival-specific marker of a bladder cancer patient comprising at least one of the following:

In another aspect of the present invention, A2ML1 gene mutation, ANAPC1 gene mutation, ARNT2 gene mutation, ASIC5 gene mutation, BIRC6 gene mutation, BTBD10 gene mutation, EDRF1 gene mutation, CFHR4 gene mutation, CLHC1 gene mutation , CTNND1 gene mutation, DCAF4 gene mutation, DHX37 gene mutation, EPAS1 gene mutation, FBN2 gene mutation, GLDC gene mutation, GRIA2 gene mutation, GUCY1A2 gene mutation, ITGA3 gene mutation, ITGA4 gene mutation , KIF19 gene mutation, KIF1B gene mutation, LPIN1 gene mutation, MAATS1 gene mutation, MCM8 gene mutation, MCTP1 gene mutation, MED1 gene mutation, MTUS2 gene mutation, NAV3 gene mutation, NME9 gene mutation , NOC3L gene mutation, NRXN3 gene mutation, PIK3C2A gene mutation, POLK gene mutation, PRKG2 gene mutation, RIN3 gene mutation, SCUBE2 gene mutation, SLC45A1 gene mutation, SORL1 gene mutation, SP4 gene mutation , TBC1D9 gene mutation, TEK gene mutation, TMC1 gene mutation, TNS3 gene mutation, TRPM3 gene mutation, TXK gene mutation, UNC13D gene mutation, ZNF207 gene mutation and ZNF282 gene mutation It provides a kit for prognostic diagnosis of bladder cancer comprising a reagent capable of detecting a survival-specific marker of a bladder cancer patient comprising at least one of the following:

Another aspect of the present invention comprises the steps of preparing a sample DNA from a sample of a bladder cancer patient; and confirming the presence or absence of a survival-specific marker using the composition for prognosis diagnosis of bladder cancer or the kit for prognosis diagnosis of bladder cancer with respect to the sample DNA; a method of providing information necessary for prognosis diagnosis of bladder cancer patients comprising a; to provide.

Using the composition for prognosis diagnosis of bladder cancer of the present invention and a kit for prognosis diagnosis of bladder cancer comprising the same, the possibility of recurrence or prognosis after treatment of bladder cancer patients can be diagnosed and predicted. This can help establish a treatment strategy for bladder cancer patients.

1 to 48 are diagrams of a bladder cancer patient with a mutation in the corresponding gene (red) and a bladder cancer patient without a mutation in the corresponding gene (blue) for each gene of the first group of candidate genes as an embodiment of the present invention. A graph of total survival and/or disease-free survival is shown.

In this specification, unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In general, the nomenclature used herein and the experimental methods described below are those well known and commonly used in the art.

In the present invention, the term 'gene' and its variants include DNA fragments involved in polypeptide chain generation; It includes regions before and after the coding region, eg promoters and 3'-untranslated regions, respectively, as well as intervening sequences (introns) between individual coding fragments (exons).

As used herein, the term 'cancer' includes any member of a class of diseases characterized by the uncontrolled growth of abnormal cells. The term includes all known cancers and neoplastic conditions, whether characterized as malignant, benign, soft tissue or solid, and cancers of all stages and grades, including cancers before and after metastasis.

In the present invention, the term 'prognosis' refers to the progress and cure of neoplastic diseases such as cancer, such as the possibility of cancer-caused death or progression, including recurrence, metastatic spread, and drug resistance, for example. For the purpose of the present invention, it may be to predict the prognosis of bladder cancer, preferably to predict the disease-free survival rate or survival rate of bladder cancer patients.

In the present invention, the term 'diagnosis' refers to confirming the presence or characteristics of a pathological condition, and for the purpose of the present invention, not only confirming whether or not cancer occurs, but also recurrence, metastasis, drug reactivity, resistance of the subject after treatment of cancer It means judging whether or not Preferably, when using the mutation of the gene of the present invention, it is possible to predict whether or not the subject will develop cancer, as well as whether the prognosis of the subject will be good in the future by checking whether the mutation is present from the subject's sample.

In the present invention, the term 'survival-specific marker' may refer to a mutation in a gene or mutations in a gene that can be an indicator for predicting the prognosis of bladder cancer in a subject after treatment of a bladder cancer patient. Also, in the present invention, the 'marker gene' may be used to refer to each gene mutation included in the survival-specific marker.

1. Composition and kit for prognostic diagnosis of bladder cancer

One aspect of the present invention provides a composition for prognostic diagnosis of bladder cancer comprising a reagent capable of detecting a survival-specific marker of a bladder cancer patient. The survival-specific marker of the composition for prognosis diagnosis of bladder cancer of the present invention may be an index predicting the prognosis of bladder cancer in a subject after treatment of a bladder cancer patient.

For example, when the survival-specific marker is identified, it can be determined that the survival rate is lower than the survival rate of a person for which the survival-specific marker is not identified, or when the survival-specific marker is identified, the recurrence rate of bladder cancer is the survival-specific marker. It can be judged that the enemy marker is higher than that of an unidentified person.

Specifically, the survival-specific markers are A2ML1 gene (Gene bank accession number: NM_144670.6) mutation, ANAPC1 gene (Gene bank accession number: NM_022662.4) mutation, ARNT2 gene (Gene bank accession number: NM_014862.4) ) mutation, ASIC5 gene (Gene bank accession number: NM_017419.3) mutation, BIRC6 gene (Gene bank accession number: NM_016252.3) mutation, BTBD10 gene (Gene bank accession number: NM_032320.6) mutation, EDRF1 Mutation of gene (Gene bank accession number: NM_015608.2), mutation of CFHR4 gene (Gene bank accession number: NM_001201550.3), mutation of gene CLHC1 (Gene bank accession number: NM_152385.4), CTNND1 gene (Gene bank accession) number: NM_001085458.2) mutation, DCAF4 gene (Gene bank accession number: NM_015604.4) mutation, DHX37 gene (Gene bank accession number: NM_032656.4) mutation, EPAS1 gene (Gene bank accession number: NM_001430.5) ) mutation, FBN2 gene (Gene bank accession number: NM_001999.4) mutation, GLDC gene (Gene bank accession number: NM_000170.2) mutation, GRIA2 gene (Gene bank accession number: NM_001083619.1) mutation, GUCY1A2 Gene bank accession number: N M_000855.3) mutation, ITGA3 gene (Gene bank accession number: NM_002204.4) mutation, ITGA4 gene (Gene bank accession number: NM_000885.6 ) mutation, KIF19 gene (Gene bank accession number: NM_153209.4) Mutation, KIF1B gene (Gene bank accession number: NM_001365951.2) mutation, LPIN1 gene (Gene bank accession number: NM_145693.4) mutation, MAATS1 gene (Gene bank accession number: NM_033364.4) mutation, MCM8 gene ( Gene bank accession number: NM_032485.6) mutation, MCTP1 gene (Gene bank accession number: NM_024717.5) mutation, MED1 gene (Gene bank accession number: NM_004774.4) mutation, MTUS2 gene (Gene bank accession number: NM_001033602.3) mutation, NAV3 gene (Gene bank accession number: NM_001024383.2) mutation, NME9 gene (Gene bank accession number: NM_178130.4) mutation, NOC3L gene (Gene bank accession number: NM_022451.11) Mutation, NRXN3 gene (Gene bank accession number: NM_001272020.2) mutation, PIK3C2A gene (Gene bank accession number: NM_002645.4) mutation, POLK gene (Gene bank accession number: NM_016218.3) mutation, PRKG2 gene ( Gene bank accession number: NM_ 006259.2) mutation, RIN3 gene (Gene bank accession number: NM_024832.5) mutation, SCUBE2 gene (Gene bank accession number: NM_020974.3) mutation, SLC45A1 gene (Gene bank accession number: NM_001080397.2) mutation, SORL1 gene (Gene bank accession number: NM_003105.6) mutation, SP4 gene (Gene bank accession number: NM_003112.5) mutation, TBC1D9 gene (Gene bank accession number: NM_015130.3) mutation, TEK gene (Gene bank) accession number: NM_000459.4) mutation, TMC1 gene (Gene bank accession number: NM_138691.2) mutation, TNS3 gene (Gene bank accession number: NM_022748.12) mutation, TRPM3 gene (Gene bank accession number: NM_206945). 5) mutation, TXK gene (Gene bank accession number: NM_003328.3) mutation, UNC13D gene (Gene bank accession number: NM_199242.2) mutation, ZNF207 gene (Gene bank accession number: NM_003457.3) mutation, ZNF282 gene (Gene bank accession number: NM_003575.4) may include at least one selected from the group consisting of mutations.

Specifically, the survival-specific marker is ANAPC1 gene mutation, BTBD10 gene mutation, DHX37 gene mutation, GRIA2 gene mutation, GUCY1A2 gene mutation, ITGA3 gene mutation, KIF19 gene mutation, KIF1B gene mutation, MAATS1 mutation of gene, mutation of MED1 gene, mutation of MTUS2 gene, mutation of NAV3 gene, mutation of NOC3L gene, mutation of PIK3C2A gene, mutation of SCUBE2 gene, mutation of SLC45A1 gene, mutation of TBC1D9 gene and mutation of ZNF282 gene It may be at least one selected from the group. For example, when at least one of the survival-specific markers is detected, the individual may determine that the survival rate is lower than that of a person for which the survival-specific marker is not identified, or it may be determined that the recurrence rate is high.

The full names of the abbreviations of the above genes are A2ML1 (alpha-2-macroglobulin like 1), ANAPC1 (anaphase promoting complex subunit 1), ARNT2 (aryl hydrocarbon receptor nuclear translocator 2), ASIC5 (acid sensing ion channel subunit family member 5), respectively. , BIRC6 (baculoviral IAP repeat containing 6), BTBD10 (BTB domain containing 10), EDRF1 (erythroid differentiation regulatory factor 1), CFHR4 (complement factor H related 4), CLHC1 (clathrin heavy chain linker domain containing 1), CTNND1 (catenin) delta 1), DCAF4 (DDB1 and CUL4 associated factor 4), DHX37 (DEAH-box helicase 37), EPAS1 (endothelial PAS domain protein 1), FBN2 (fibrillin 2), GLDC (glycine decarboxylase), GRIA2 (glutamate ionotropic receptor AMPA) type subunit 2), GUCY1A2 (guanylate cyclase 1 soluble subunit alpha 2), ITGA3 (integrin subunit alpha 3), ITGA4 (integrin subunit alpha 4), KIF19 (kinesin family member 19), KIF1B (kinesin family member 1B), LPIN1 ( lipin 1), MAATS1 (MYCBP associated and testis expressed 1), MCM8 (minichromosome maintenance 8 homologous recombination r epair factor), multiple C2 and transmembrane domain containing 1 (MCTP1), mediator complex subunit 1 (MED1), microtubule associated scaffold protein 2 (MTUS2), neuron navigator 3 (NAV3), NME9 (NME/NM23 family member 9), NOC3L (NOC3 like DNA replication regulator), NRXN3 (neurexin 3), PIK3C2A (phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alpha), POLK (DNA polymerase kappa), PRKG2 (protein kinase cGMP-dependent 2), RIN3 ( Ras and Rab interactor 3), SCUBE2 (signal peptide, CUB domain and EGF like domain containing 2), SLC45A1 (solute carrier family 45 member 1), SORL1 (sortilin related receptor 1), SP4 (Sp4 transcription factor), TBC1D9 (TBC1) domain family member 9), TEK (TEK receptor tyrosine kinase), TMC1 (transmembrane channel like 1), TNS3 (tensin 3), TRPM3 (transient receptor potential cation channel subfamily M member 3), TXK (TXK tyrosine kinase), UNC13D ( unc-13 homolog D), ZNF207 (zinc finger protein 207), or ZNF282 (zinc finger protein 282).

In the present invention, the reagent capable of detecting the survival-specific marker may include one or more selected from the group consisting of a primer, a probe, an antibody, and an aptamer for the survival-specific marker. The primer, probe, antibody or aptamer can be manufactured using a known technique, and a primer, probe, antibody or aptamer capable of detecting a mutation of a gene of the present invention is included in the scope of the present invention.

In the present invention, the term 'primer' is a nucleic acid sequence having a short free 3' hydroxyl group, which can form a base pair with a complementary template and is a starting point for template strand copying. It refers to a short nucleic acid sequence that functions as The primers are capable of initiating DNA synthesis in the presence of reagents for the polymerization reaction (ie, DNA polymerase or reverse transcriptase) and the four different nucleoside triphosphates in appropriate buffer solutions and temperatures. In the present invention, PCR amplification is performed using the forward and reverse primers of the mutant gene to determine the presence or absence of a corresponding gene marker through the generation of a desired product, and it can be used for diagnosis. For example, in the case of a forward primer, a primer corresponding to a mutant in which deletion, substitution, or insertion has occurred is designed, and a reverse primer is designed and PCR corresponding to a position where mutation does not occur, mutation of the gene of the present invention In the case of a chain, an amplification product will be generated by PCR, but if it is not a mutant of the gene of the present invention, no amplification product will be generated. PCR conditions, forward and reverse primer lengths can be modified based on those known in the art.

In the present invention, the term 'probe' refers to a nucleic acid fragment such as RNA or DNA capable of forming a specific binding with DNA, and consists of several bases to several hundred bases as long as possible. Since the probe is labeled, the presence or absence of a specific DNA can be confirmed. The probe may be manufactured in the form of an oligonucleotide probe, a single stranded DNA probe, a double stranded DNA probe, an RNA probe, or the like. In the present invention, by performing hybridization using a probe complementary to a mutation in a gene, it is possible to diagnose whether bladder cancer recurs based on whether or not hybridization occurs. For example, when a probe corresponding to a mutant having a deletion, substitution or insertion is synthesized and the probe is hybridized with the genomic DNA of a bladder cancer patient, hybridization will occur in the case of a mutant of the gene of the present invention, but If the gene is not a mutant, hybridization will not occur. Selection of suitable probes and hybridization conditions can be modified based on those known in the art.

In the present invention, the term 'antibody' is a term known in the art and refers to a specific protein molecule directed against an antigenic site. In the present invention, the antibody may refer to an antibody that specifically binds to each marker gene. Such an antibody can be prepared by cloning each marker gene into an expression vector according to a conventional method to obtain a protein encoded by the marker gene, and from the obtained protein by a conventional method. This also includes a partial peptide that can be made from the protein, and the partial peptide of the present invention contains at least 7 amino acids, preferably 9 amino acids, more preferably 12 or more amino acids. The form of the antibody of the present invention is not particularly limited, and a part thereof is included in the antibody of the present invention as long as it has polyclonal antibody, monoclonal antibody, or antigen-binding property, and all immunoglobulin antibodies are included. Furthermore, the antibody of the present invention includes a special antibody such as a humanized antibody. Antibodies used for the detection of marker genes of the present invention include functional fragments of antibody molecules as well as complete forms having two full-length light chains and two full-length heavy chains. A functional fragment of an antibody molecule refers to a fragment having at least an antigen-binding function, and includes Fab, F(ab'), F(ab') ₂ and Fv.

As used herein, the term 'aptamer' refers to a single-stranded nucleic acid (DNA, RNA, or modified nucleic acid) that has a stable tertiary structure by itself and can bind to a target molecule with high affinity and specificity. Aptamers can be synthesized by known chemical methods, for example, by a method called SELEX (Systematic Evolution of Ligands of Exponential enrichment) for various target substances (proteins, sugars, dyes, DNA, metal ions, cells, etc.) You can develop aptamers.

The mutation of the gene may include any one or more mutations, for example, a truncating mutation, a missense mutation (or a missense mutation), a nonsense mutation, a frame shift. ) mutation, in-frame mutation (or in-frame mutation), splice mutation, and splice_region mutation may have at least one mutation selected from the group consisting of mutations. The frameshift mutation may be at least one of a frame shift insert (FS ins) mutation and a frame shift delete mutation (FS del). The in-frame mutation may be at least one of an in-frame insertion (IF ins) mutation and an in-frame delete (IF del) mutation.

The term "X#Y" with respect to a mutation in a polypeptide sequence is self-recognized in the art, where "#" indicates the mutation site with respect to the amino acid number of the polypeptide, and "X" is that of the wild-type amino acid sequence. indicates the amino acid found at that position, and "Y" indicates the mutant amino acid at that position. For example, the designation " R807H " with respect to the A2ML1 polypeptide indicates that arginine is present at amino acid number 807 of the wild-type A2ML1 sequence and that arginine has been replaced with histidine in the mutant A2ML1 sequence. Mutations in these genes are as follows:

The mutation of the A2ML1 gene is, in the amino acid sequence of SEQ ID NO: 1, R807H missense mutation, E222K missense mutation, P1341Q missense mutation, Q1305* nonsense mutation, P176S missense mutation, E202K missense mutation, L522R missense mutation, T1312M missense mutation, P1377A missense mutation, L1124F missense mutation, W763S missense mutation or S718L missense mutation. In the nonsense mutation, * indicates that the amino acid synthesis at the corresponding amino acid position is terminated (the description is omitted below).

The mutation of the ANAPC1 gene is, in the amino acid sequence of SEQ ID NO: 2, S736L missense mutation, S1530L missense mutation, S341L missense mutation, Q846P missense mutation, L1662I missense mutation, Y583* nonsense mutation, L1657F missense mutation, K798T missense mutation, D568G missense mutation, S156I missense mutation, L271V missense mutation, Q846* nonsense mutation, Q827* nonsense mutation, K1066Rfs*17 frameshift deletion mutation, E146Q missense mutation, T1264Qfs*14 frameshift deletion mutation, R527W missense mutation, S470L missense mutation or M934I missense mutation. The notation method for frameshift mutations is amino acid type (amino acid position) amino acid type fs* (number of nucleotides from the amino acid position to the stop codon in the downstream direction) explanation is omitted).

The mutation of the ARNT2 gene is, in the amino acid sequence of SEQ ID NO: 3, D344G missense mutation, S654L missense mutation, T575A missense mutation, L366V missense mutation, D549N missense mutation, E193K missense mutation, A127T missense mutation, E137K missense mutation, M294I missense mutation or Q571H missense mutation.

The mutation of the ASIC5 gene is, in the amino acid sequence of SEQ ID NO: 4, P31A missense mutation, Q305K missense mutation, P294H missense mutation, L64F missense mutation, P491A missense mutation, Y472* nonsense mutation, P490R missense mutation, D250N missense mutation or H323Y missense mutation.

The mutation of the BIRC6 gene is, in the amino acid sequence of SEQ ID NO: 5, S464L missense mutation, S4205L missense mutation, R1789I missense mutation, R4400W missense mutation, R4732* nonsense mutation, E1723K missense mutation, P2756R missense mutation, L2766V Missense mutation, D3628H missense mutation, A3599T missense mutation, S1500N missense mutation, E755K missense mutation, Q3827* nonsense mutation, S321C missense mutation, L1566V missense mutation, N2735H missense mutation, D448N missense mutation, M418I Missense mutation, M3472I missense mutation, R4713L missense mutation, R4713L missense mutation, D1418Y missense mutation, G1465E missense mutation, D1504N missense mutation, L3858F missense mutation, H3859Y missense mutation, L3870V missense mutation, L3768V Missense mutation, E1825Q missense mutation, S2862L missense mutation, Q317E missense mutation, H3493N missense mutation, S461C missense mutation, G3485V missense mutation, G3485S missense mutation, K3894T missense mutation, S440L missense mutation, D1803N Missense mutation, Q4108E missense mutation, Q4634E missense mutation, S4593L missense mutation, S4592F missense mutation, M3052I missense mutation, T3988A missense mutation, E3242K missense mutation, S2883L missense mutation, V3693Yfs*10 frameshift deletion Mutation, E4428Q missense mutation, L2358F missense mutation, S3504G missense mutation, D4822N missense mutation, L2508V missense mutation, E4486Q missense mutation, E4826* Nonsense mutation, P2609L missense mutation, L4689M missense mutation, S3740L missense mutation, W2403C missense mutation, L4698R missense mutation, S480L missense mutation, E164G missense mutation, D2414H missense mutation, S4586L missense mutation, L4612V miss Sense mutation, Q1060E missense mutation, R276G missense mutation, E499K missense mutation, S581L missense mutation, L1703F missense mutation, L632F missense mutation, E2861K missense mutation, L3214F missense mutation, L4239S missense mutation or M3347I miss It may be a sense mutation.

The mutation of the BTBD10 gene is, in the amino acid sequence of SEQ ID NO: 6, R388L missense mutation, E260Q missense mutation, R352T missense mutation, Q302H missense mutation, R27C missense mutation, M292I missense mutation, R64T missense mutation or S404Y It may be a missense mutation.

The mutation of the EDRF1 gene is, in the amino acid sequence of SEQ ID NO: 7, G217V missense mutation, E197Q missense mutation, E894Q missense mutation, K1179N missense mutation, E648K missense mutation, S206C missense mutation, D801V missense mutation, D532N missense mutation, Q757H missense mutation, Y696C missense mutation or P451Q missense mutation.

The mutation of the CFHR4 gene is, in the amino acid sequence of SEQ ID NO: 8, E427* nonsense mutation, L560V missense mutation, E194K missense mutation, I512L missense mutation, G64E missense mutation, S241F missense mutation, E244* nonsense mutation, N161K missense mutation, E124K missense mutation, E401Q missense mutation, Q528L missense mutation, T449K missense mutation or D442N missense mutation.

The mutation of the CLHC1 gene is, in the amino acid sequence of SEQ ID NO: 9, Y427* nonsense mutation, S398C missense mutation, R115T missense mutation, A318S missense mutation, A577T missense mutation, E380Q missense mutation, Q445H missense mutation, L395Q missense mutation, R563Q missense mutation or D148Y missense mutation.

The mutation of the CTNND1 gene is, in the amino acid sequence of SEQ ID NO: 10, L944V missense mutation, S767F missense mutation, X474_splice Splice_Site mutation (c.1421-2A>G), S670L missense mutation, L497Cfs*13 frameshift deletion mutation, D293N missense mutation, L759Rfs*12 frameshift deletion mutation, R364T missense mutation, S571L missense mutation or Q708* nonsense mutation.

The mutation of the DCAF4 gene may be an X179_splice Splice_Site mutation (c.535-1G>C), a R439K missense mutation, or an E74K missense mutation in the amino acid sequence of SEQ ID NO: 11.

The mutation of the DHX37 gene may be, in the amino acid sequence of SEQ ID NO: 12, V265M missense mutation, K525N missense mutation, E560Q missense mutation, Q287* nonsense mutation, V635M missense mutation, E1056Q missense mutation or P916L missense mutation. have.

The mutation of the EPAS1 gene may be an R690Q missense mutation, a D107N missense mutation, a K7R missense mutation or a G792R missense mutation in the amino acid sequence of SEQ ID NO: 13.

The mutation of the FBN2 gene is, in the amino acid sequence of SEQ ID NO: 14, E2423Q missense mutation, P740L missense mutation, E1144K missense mutation, X2294_splice Splice_Site mutation (c.6881-1G>C), E252Q missense mutation, E1939K missense mutation, F1670Lfs*66 frameshift deletion mutation, I853M missense mutation, G1520S missense mutation, E1118* nonsense mutation, R2329* nonsense mutation, D2294N missense mutation, E1036K missense mutation, Q2791H missense mutation, D1858H missense mutation, S597T missense mutation, T2538K missense mutation, D1538Y missense mutation, D1534N missense mutation, X1532_splice Splice_Site mutation (c.4595-1G> A), S2178N missense mutation, D1493H missense mutation, E1286Q missense mutation, C1833S missense mutation, D2215N missense mutation, E2795* nonsense mutation, C1434S missense mutation, E2177Q missense mutation, H307D missense mutation, A1028V miss a sense mutation, a P1469L missense mutation, an R64C missense mutation, an E1637K missense mutation, an E2306_G2309del in-frame deletion mutation or a D1694H missense mutation. In the notation method of in-frame deletion mutations, del indicates that the corresponding amino acid is deleted at the corresponding amino acid sequence position (the description is omitted below).

The mutation of the GLDC gene is, in the amino acid sequence of SEQ ID NO: 15, R506T missense mutation, F870L missense mutation, S401F missense mutation, D436H missense mutation, G156V missense mutation, S401Y missense mutation, Q385* nonsense mutation or S492L It may be a missense mutation.

The mutation of the GRIA2 gene is, in the amino acid sequence of SEQ ID NO: 16, R45Q missense mutation, E412Q missense mutation, I819V missense mutation, K716T missense mutation, L139F missense mutation, K850N missense mutation, S585T missense mutation, E190K It may be a missense mutation or an N482D missense mutation.

The mutation of the GUCY1A2 gene is, in the amino acid sequence of SEQ ID NO: 17, H183Y missense mutation, E669Q missense mutation, S525L missense mutation, S101L missense mutation, L710V missense mutation, L162=Splice_Region mutation (c.486C>T) , S101W missense mutation, G343V missense mutation, Q462H missense mutation, L594F missense mutation, R172T missense mutation, Q217Hfs*32 frameshift deletion mutation or R655del in-frame deletion mutation.

The mutation of the ITGA3 gene may be, in the amino acid sequence of SEQ ID NO: 18, P845H missense mutation, E63K missense mutation, H356Y missense mutation, X714_splice Splice_Site mutation, F543L missense mutation, W220C missense mutation or S202G missense mutation. .

The mutation of the ITGA4 gene is, in the amino acid sequence of SEQ ID NO: 19, G431E missense mutation, G451R missense mutation, R12Q missense mutation, T674A missense mutation, E137K missense mutation, D287N missense mutation, R553T missense mutation, T615Qfs *2 Frameshift deletion mutation, D439N missense mutation, E957D missense mutation, S653G missense mutation, S537C missense mutation, S433C missense mutation, S435* nonsense mutation, X186_splice Splice_Site mutation, G303E missense mutation, Y1024N missense mutation , X780_splice Splice_Site mutation or L992V missense mutation.

The mutation of the KIF19 gene is, in the amino acid sequence of SEQ ID NO: 20, G643D missense mutation, X770_splice Splice_Site mutation (c.2309-1G>C), E770D missense mutation, Q126H missense mutation, G412R missense mutation, A853V missense mutation mutation, E630Kfs*45 frameshift deletion mutation, E852Q missense mutation, R172L missense mutation or R791W missense mutation.

The mutation of the KIF1B gene is, in the amino acid sequence of SEQ ID NO: 21, K478 = Splice_Region mutation (c.1434G>A), E1685K missense mutation, X295_splice Splice_Site mutation (c.883-1G>C), E708* nonsense mutation, E655K Missense mutation, F887L missense mutation, N71K missense mutation, Q70E missense mutation, E239K missense mutation, Q29* nonsense mutation, E1018D missense mutation, E645Q missense mutation, R1515C missense mutation, T949M missense mutation, G554E a missense mutation, a K1097N missense mutation, a D302H missense mutation or a P532A missense mutation.

The mutation of the LPIN1 gene may be, in the amino acid sequence of SEQ ID NO: 22, A613T missense mutation, L667V missense mutation, S889L missense mutation, S889L missense mutation, G9S missense mutation, E773Q missense mutation or K168N missense mutation. have.

The mutation of the MAATS1 gene is, in the amino acid sequence of SEQ ID NO: 23, E758K missense mutation, D452H missense mutation, K349N missense mutation, K454N missense mutation, E130Q missense mutation, E666K missense mutation, P464Lfs*21 frameshift deletion mutation or S185* nonsense mutation.

The mutation of the MCM8 gene is, in the amino acid sequence of SEQ ID NO: 24, R309Q missense mutation, L689F missense mutation, E100Q missense mutation, I107S missense mutation, P252R missense mutation, E174Q missense mutation, D184N missense mutation, G185E missense mutation, E4Q missense mutation, S497C missense mutation, R22T missense mutation or K126E missense mutation.

The mutation of the MCTP1 gene is, in the amino acid sequence of SEQ ID NO: 25, R480K missense mutation, V418M missense mutation, S599F missense mutation, N304I missense mutation, S169L missense mutation, K771I missense mutation, E863K missense mutation, V495M missense mutation, R529T missense mutation, E765Q missense mutation or D860H missense mutation.

The mutation of the MED1 gene is, in the amino acid sequence of SEQ ID NO: 26, H1526D missense mutation, S387T missense mutation, S1227L missense mutation, S1379L missense mutation, S1218C missense mutation, K202N missense mutation, L69I missense mutation, K283T Missense mutation, S1375C missense mutation, P1208A missense mutation, S256* nonsense mutation, S682L missense mutation, S1363* nonsense mutation, S1439F missense mutation, S1558* nonsense mutation, P381A missense mutation, S1368F missense mutation, E8K missense mutation, S1111L missense mutation, S349L missense mutation or M1172I missense mutation.

The mutation of the MTUS2 gene is, in the amino acid sequence of SEQ ID NO: 27, K741T missense mutation, D444N missense mutation, K1330del in-frame deletion mutation, L935I missense mutation, E163* nonsense mutation, E180K missense mutation, D417H missense mutation, R29K missense mutation, G223E missense mutation, R109T missense mutation, R160S missense mutation, E268D missense mutation, E398K missense mutation or L688F missense mutation.

The mutation of the NAV3 gene is, in the amino acid sequence of SEQ ID NO: 28, S1262C missense mutation, S1273L missense mutation, E48* nonsense mutation, E1023Q missense mutation, S1090F missense mutation, S1106L missense mutation, D1690H missense mutation, S1170C Missense mutation, E1603K missense mutation, L692F missense mutation, Q2363L missense mutation, Y2151C missense mutation, D1969H missense mutation, A1679V missense mutation, L29V missense mutation, S1262F missense mutation, S1217F missense mutation, S461C Missense mutation, S1722F missense mutation, S532Y missense mutation, I100M missense mutation, S210L missense mutation, R1402T missense mutation, N732S missense mutation, S1142L missense mutation, S136F missense mutation, T1080S missense mutation, E1563K missense mutation, Y820Vfs*20 frameshift deletion mutation, G1384D missense mutation or S2364C missense mutation.

The mutation of the NME9 gene may be an E139K missense mutation, an E188Q missense mutation, an E194Q missense mutation, an S297N missense mutation or an E67K missense mutation in the amino acid sequence of SEQ ID NO: 29.

The mutation of the NOC3L gene is, in the amino acid sequence of SEQ ID NO: 30, S456C missense mutation, I155M missense mutation, H636Y missense mutation, N6T missense mutation, L662M missense mutation, L457V missense mutation, D172G missense mutation, D113H missense mutation, S115F missense mutation, E128K missense mutation or Q668H missense mutation.

The mutation of the NRXN3 gene is, in the amino acid sequence of SEQ ID NO: 31, D359Y missense mutation, M319I missense mutation, I444V missense mutation, A53V missense mutation, S229C missense mutation, D505H missense mutation, D41H missense mutation, X34_splice Splice_Site mutation (c.102+1G>C), A194D missense mutation or Y84C missense mutation.

The mutation of the PIK3C2A gene is, in the amino acid sequence of SEQ ID NO: 32, L1652V missense mutation, D839N missense mutation, A1501G missense mutation, I1475V missense mutation, Q1349E missense mutation, L1034V missense mutation, R1570* nonsense mutation, Q434 * Nonsense mutation, R1259* nonsense mutation, D870N missense mutation, S702* nonsense mutation, D25Y missense mutation, S1457L missense mutation, Q770K missense mutation, S259F missense mutation, D846H missense mutation, E865K missense mutation or S128L It may be a missense mutation.

The mutation of the POLK gene is, in the amino acid sequence of SEQ ID NO: 33, S696Y missense mutation, F567L missense mutation, E180Q missense mutation, M133I missense mutation, I371T missense mutation, E272K missense mutation, E560K missense mutation, P250Q missense mutation, S747C missense mutation, E94K missense mutation, S745C missense mutation or K158N missense mutation.

The mutation of the PRKG2 gene is, in the amino acid sequence of SEQ ID NO: 34, R27W missense mutation, F555L missense mutation, A532D missense mutation, G652R missense mutation, K288N missense mutation, A417 = Splice_Region mutation (c.1251G>A) , D742H missense mutation, T322S missense mutation or E402K missense mutation.

The mutation of the RIN3 gene is, in the amino acid sequence of SEQ ID NO: 35, E134Q missense mutation, R645C missense mutation, P202L missense mutation, W233R missense mutation, Q744H missense mutation, I695M missense mutation, X84_splice Splice_Site mutation (c. 250-1G>C), E423Q missense mutation or V679A missense mutation.

The mutation of the SCUBE2 gene is, in the amino acid sequence of SEQ ID NO: 36, G234V missense mutation, D766N missense mutation, D47H missense mutation, S635L missense mutation, H182N missense mutation, I926M missense mutation, E93Q missense mutation, E535K It may be a missense mutation or an X668_splice Splice_Site mutation (c.2003-1G>A).

The mutation of the SLC45A1 gene is, in the amino acid sequence of SEQ ID NO: 37, D220N missense mutation, Q657* nonsense mutation, A687S missense mutation, P295L missense mutation, L690V missense mutation, E98Q missense mutation, A274E missense mutation, A587V missense mutation, G619R missense mutation, Q81H missense mutation or S499F missense mutation.

The mutation of the SORL1 gene is, in the amino acid sequence of SEQ ID NO: 38, L1831V missense mutation, P1751L missense mutation, W1342* nonsense mutation, S375* nonsense mutation, S776L missense mutation, I599M missense mutation, S149* nonsense mutation, S2206L missense mutation, E348Q missense mutation, W1096C missense mutation, C1040* nonsense mutation, G2152E missense mutation, E451* nonsense mutation, Q1062* nonsense mutation or V1807Sfs*11 frameshift insertion mutation.

The mutation of the SP4 gene is, in the amino acid sequence of SEQ ID NO: 39, S310F missense mutation, K705N missense mutation, R621Q missense mutation, L722V missense mutation, R234T missense mutation, E782K missense mutation, Q250E missense mutation, S187L It may be a missense mutation or an S122C missense mutation.

The mutation of the TBC1D9 gene is, in the amino acid sequence of SEQ ID NO: 40, E156Q missense mutation, K993N missense mutation, E18K missense mutation, K1098N missense mutation, L286V missense mutation, S292N missense mutation, E411Q missense mutation or E689Q It may be a missense mutation.

The mutation of the TEK gene is, in the amino acid sequence of SEQ ID NO: 41, L9F missense mutation, N722K missense mutation, G548A missense mutation, S164L missense mutation, L911M missense mutation, Y816D missense mutation, P445T missense mutation, E571K a missense mutation, a G744E missense mutation or a P447T missense mutation.

The mutation of the TMC1 gene may be R264Q missense mutation, S697L missense mutation, G267A missense mutation, L450F missense mutation, R46K missense mutation, E118Q missense mutation or R512G missense mutation in the amino acid sequence of SEQ ID NO: 42. have.

The mutation of the TNS3 gene is, in the amino acid sequence of SEQ ID NO: 43, Q205E missense mutation, S119L missense mutation, X158_splice Splice_Site mutation (c.474-1G>A), S916L missense mutation, S916L missense mutation, N465I missense mutation mutation, S499L missense mutation, P686R missense mutation, D532H missense mutation, E1100K missense mutation, D1140Y missense mutation, S843L missense mutation, G679D missense mutation or E435Q missense mutation.

The mutation of the TRPM3 gene is, in the amino acid sequence of SEQ ID NO: 44, D603N missense mutation, R429W missense mutation, E816Q missense mutation, I1149V missense mutation, R835Q missense mutation, R1634C missense mutation, Y1638C missense mutation, S1341L Missense mutation, R1262C missense mutation, E638* nonsense mutation, A675T missense mutation, D1185N missense mutation, G90V missense mutation, E920K missense mutation, X86_splice Splice_Site mutation (c.258-1G>A), M1242I missense mutation, A680D missense mutation, D1186N missense mutation, F144I missense mutation, T406S missense mutation, G568E missense mutation, E123Q missense mutation or R37G missense mutation.

The mutation of the TXK gene is, in the amino acid sequence of SEQ ID NO: 45, S407* nonsense mutation, S400L missense mutation, H323L missense mutation, X149_splice Splice_Site mutation (c.447-2A>G), L163V missense mutation, E481K missense mutation mutation, G463V missense mutation, D267Y missense mutation, E217K missense mutation, Q204* nonsense mutation or D408G missense mutation.

The mutation of the UNC13D gene is, in the amino acid sequence of SEQ ID NO: 46, Q736* nonsense mutation, A1089T missense mutation, E1017K missense mutation, E1017K missense mutation, L223M missense mutation, D497H missense mutation, S345F missense mutation, D258N missense mutation, R234W missense mutation or E80K missense mutation.

The mutation of the ZNF207 gene is, in the amino acid sequence of SEQ ID NO: 47, A64G missense mutation, E23K missense mutation, Y382C missense mutation, Q28R missense mutation, L97F missense mutation, S121C missense mutation, E374Q missense mutation, D21N It may be a missense mutation or a D114N missense mutation.

The mutation of the ZNF282 gene may be a P187L missense mutation, a N591K missense mutation, a K150Q missense mutation, a G512C missense mutation, a V108M missense mutation, a D135N missense mutation or an E634K missense mutation in the amino acid sequence of SEQ ID NO: 48. have.

Next generation sequencing (NGS), RT-PCR, direct nucleic acid sequencing method, and microarray can be used as an analysis method for diagnosing the prognosis of bladder cancer using the mutation of the gene, and the gene of the present invention Any method that can confirm the presence of a mutation using a mutation of In one embodiment, the presence of a mutation is determined using an anti-(mutant of each gene) antibody or nucleic acid probe that hybridizes under stringent conditions to the polynucleotide of the mutant of each gene. In another embodiment, the antibody or nucleic acid probe is detectably labeled. In another embodiment, the label is selected from the group consisting of an immunofluorescent label, a chemiluminescent label, a phosphorescent label, an enzymatic label, a radioactive label, avidin/biotin, colloidal gold particles, colored particles, and magnetic particles. In another embodiment, the presence of the mutation is determined by radioimmunoassay, western blot assay, immunofluorescence assay, enzymatic immunoassay, immunoprecipitation assay, chemiluminescence assay, immunohistochemical assay, dot blot assay, slot blot assay or flow cytometry. determined by the assay. In another embodiment, the presence of the mutation is determined by RT-PCR. In another embodiment, the presence of a mutation is determined by nucleic acid sequencing.

As used herein, the term 'polynucleotide' generally refers to any polyribonucleotide or polydeoxyribonucleotide, which may be unmodified RNA or DNA or modified RNA or DNA. Thus, for example, polynucleotides as defined herein include, but are not limited to, single- and double-stranded DNA, DNA comprising single- and double-stranded regions, single- and double-stranded RNA, and single- and double-stranded DNA. - RNA comprising a region, single-stranded or more typically double-stranded, or hybrid molecule comprising DNA and RNA, which may comprise single- and double-stranded regions. Thus, DNA or RNA having a backbone that has been modified for stability or other reasons is a 'polynucleotide' as the term is intended herein. Also included in the term 'polynucleotide' as defined herein is DNA or RNA comprising an unconventional base such as inosine or a modified base such as a tritiated base. In general, the term 'polynucleotide' includes all chemically, enzymatically and/or metabolically modified forms of unmodified polynucleotides. Polynucleotides can be prepared by a variety of methods, including in vitro recombinant DNA-mediated techniques, and by expression of DNA in cells and organisms.

In another aspect of the present invention, A2ML1 gene mutation, ANAPC1 gene mutation, ARNT2 gene mutation, ASIC5 gene mutation, BIRC6 gene mutation, BTBD10 gene mutation, EDRF1 gene mutation, CFHR4 gene mutation, CLHC1 gene mutation , CTNND1 gene mutation, DCAF4 gene mutation, DHX37 gene mutation, EPAS1 gene mutation, FBN2 gene mutation, GLDC gene mutation, GRIA2 gene mutation, GUCY1A2 gene mutation, ITGA3 gene mutation, ITGA4 gene mutation , KIF19 gene mutation, KIF1B gene mutation, LPIN1 gene mutation, MAATS1 gene mutation, MCM8 gene mutation, MCTP1 gene mutation, MED1 gene mutation, MTUS2 gene mutation, NAV3 gene mutation, NME9 gene mutation , NOC3L gene mutation, NRXN3 gene mutation, PIK3C2A gene mutation, POLK gene mutation, PRKG2 gene mutation, RIN3 gene mutation, SCUBE2 gene mutation, SLC45A1 gene mutation, SORL1 gene mutation, SP4 gene mutation , TBC1D9 gene mutation, TEK gene mutation, TMC1 gene mutation, TNS3 gene mutation, TRPM3 gene mutation, TXK gene mutation, UNC13D gene mutation, ZNF207 gene mutation and ZNF282 gene mutation It provides a kit for prognostic diagnosis of bladder cancer comprising a reagent capable of detecting a survival-specific marker of a bladder cancer patient comprising at least one of the following:

Specifically, the survival-specific marker is ANAPC1 gene mutation, BTBD10 gene mutation, DHX37 gene mutation, GRIA2 gene mutation, GUCY1A2 gene mutation, ITGA3 gene mutation, KIF19 gene mutation, KIF1B gene mutation, MAATS1 mutation of gene, mutation of MED1 gene, mutation of MTUS2 gene, mutation of NAV3 gene, mutation of NOC3L gene, mutation of PIK3C2A gene, mutation of SCUBE2 gene, mutation of SLC45A1 gene, mutation of TBC1D9 gene and mutation of ZNF282 gene It may be at least one selected from the group. For example, when at least one of the survival-specific markers is detected, the individual may determine that the survival rate is lower than that of a person for which the survival-specific marker is not identified, or it may be determined that the recurrence rate is high.

The reagent capable of detecting the survival-specific marker may include one or more selected from the group consisting of a primer, a probe, an antibody, and an aptamer, and the specific details are the same as described above, and thus a detailed description thereof will be omitted.

The kit of the present invention may be an RT-PCR kit, a DNA chip kit or a protein chip kit. As an example, the RT-PCR kit for measuring the mRNA expression level of the marker gene of the present invention may be a kit including essential elements necessary for performing RT-PCR. The RT-PCR kit contains, in addition to each primer pair specific for the marker gene, a test tube or other suitable container, reaction buffer (with varying pH and magnesium concentration), deoxynucleotides (dNTPs), Taq-polymerase and enzymes such as reverse transcriptase, DNase, RNAse inhibitors, DEPC-water, sterile water, and the like. In addition, a pair of primers specific to a gene used as a quantitative control may be included.

As another example, the DNA chip kit of the present invention may include essential elements necessary for performing a DNA chip analysis method. The DNA chip kit may include a substrate to which cDNA corresponding to a marker gene or a fragment thereof is attached as a probe, and reagents, agents, enzymes, and the like for producing a fluorescently labeled probe. In addition, the substrate may include cDNA corresponding to a quantitative control gene or a fragment thereof.

As another example, the kit of the present invention is a protein chip kit for measuring the level of a protein expressed from the marker gene, and the kit is not particularly limited thereto, but includes a substrate, an appropriate buffer, It may include a chromogenic enzyme or a secondary antibody labeled with a fluorescent substance, a chromogenic substrate, and the like. The substrate is not particularly limited thereto, but a nitrocellulose membrane, a 96-well plate synthesized from a polyvinyl resin, a 96-well plate synthesized from a polystyrene resin, a glass slide glass, etc. may be used, and the chromogenic enzyme is not particularly limited thereto. However, peroxidase and alkaline phosphatase may be used, and the fluorescent material may be FITC, RITC, etc., but is not particularly limited thereto, and the color development substrate solution is not particularly limited thereto, but ABTS (2, 2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) or OPD (o-phenylenediamine), TMB (tetramethyl benzidine).

In addition, the kit of the present invention may further include a buffer, an indicator, or a combination thereof as a reagent.

The kit for prognostic diagnosis of bladder cancer of the present invention is very economical because it saves time and money compared to the existing general gene mutation detection method. Using existing gene mutation detection methods such as Single Strand Conformational Polymorphism (SSCP), Protein Truncation Test (PTT), cloning, and direct sequencing, it takes several days on average to test all one gene. It takes several months. In addition, gene mutations can be precisely tested quickly and simply through next generation sequencing (NGS). When mutations are tested by conventional analysis methods such as SSCP, cloning, direct sequencing, and Restriction Fragment Length Polymorphism (RFLP), it takes about a month to complete the test, whereas using the kit of the present invention, sample DNA is prepared If it is done, results can be obtained within about 10 to 11 hours, and since a primer set capable of detecting mutations is integrated on one chip, not only time but also cost can be reduced compared to the conventional method. Compared to the conventional method, the average cost of reagents is less than half per experiment, so even greater cost savings can be expected when the researcher's labor costs are taken into account.

2. A method of providing necessary information for prognostic diagnosis of bladder cancer

Another aspect of the present invention comprises the steps of preparing a sample DNA from a sample of a bladder cancer patient; It provides a method of providing information necessary for prognostic diagnosis of bladder cancer patients, including: confirming the presence or absence of a survival-specific marker using the sample DNA for prognosis diagnosis of bladder cancer.

The method may further include amplifying the sample DNA prepared from the bladder cancer patient's sample using the composition or kit for prognostic diagnosis of bladder cancer.

The description of the ' composition and kit for prognostic diagnosis of bladder cancer' is the same as that described in '1. Composition and kit for prognostic diagnosis of bladder cancer ', so a detailed description will be omitted.

The term 'patient' usually includes humans as well as other animals, such as other primates, rodents, dogs, cats, horses, sheep, pigs, and the like.

The term 'sample' refers to a sample of an individual or tissue in which cancer or tumor has already occurred or is expected to occur, and a target sample for diagnosing its prognosis. Specifically, it may refer to a tumor lysate or extract prepared from frozen tissue obtained from a patient with bladder cancer.

The term 'subject' includes a subject diagnosed with or suspected of having bladder cancer.

The method can predict the overall survival or disease-free survival of bladder cancer patients.

As used herein, the term 'overall survival (OS)' includes a clinical endpoint describing a patient who is alive for a finite time after being diagnosed with or treated for a disease, such as cancer, regardless of whether the cancer recurs or not. means the possibility of surviving.

In the present invention, the term 'disease-free survival (DFS)' includes a period in which a patient survives without cancer recurrence after treatment for a specific disease (eg, cancer).

According to the present invention, by confirming the presence of a mutation in the gene of the present invention in a sample of a bladder cancer patient, it is possible to predict what prognosis an individual having the target sample has for cancer. This method can also be achieved by comparing the total survival or disease-free survival of subjects in a control group that does not have a mutation known to have a good prognosis. In the present invention, an individual known to have a good prognosis means an individual without a history of metastasis, recurrence, death, etc. after cancer has developed.

The survival-specific markers are A2ML1 gene mutation, ANAPC1 gene mutation, ARNT2 gene mutation, ASIC5 gene mutation, BIRC6 gene mutation, BTBD10 gene mutation, EDRF1 gene mutation, CFHR4 gene mutation, CLHC1 gene mutation , CTNND1 gene mutation, DCAF4 gene mutation, DHX37 gene mutation, EPAS1 gene mutation, FBN2 gene mutation, GLDC gene mutation, GRIA2 gene mutation, GUCY1A2 gene mutation, ITGA3 gene mutation, ITGA4 gene mutation , KIF19 gene mutation, KIF1B gene mutation, LPIN1 gene mutation, MAATS1 gene mutation, MCM8 gene mutation, MCTP1 gene mutation, MED1 gene mutation, MTUS2 gene mutation, NAV3 gene mutation, NME9 gene mutation , NOC3L gene mutation, NRXN3 gene mutation, PIK3C2A gene mutation, POLK gene mutation, PRKG2 gene mutation, RIN3 gene mutation, SCUBE2 gene mutation, SLC45A1 gene mutation, SORL1 gene mutation, SP4 gene mutation , TBC1D9 gene mutation, TEK gene mutation, TMC1 gene mutation, TNS3 gene mutation, TRPM3 gene mutation, TXK gene mutation, UNC13D gene mutation, ZNF207 gene mutation and ZNF282 gene mutation It may include at least one of

Specifically, the survival-specific marker is ANAPC1 gene mutation, BTBD10 gene mutation, DHX37 gene mutation, GRIA2 gene mutation, GUCY1A2 gene mutation, ITGA3 gene mutation, KIF19 gene mutation, KIF1B gene mutation, MAATS1 mutation of gene, mutation of MED1 gene, mutation of MTUS2 gene, mutation of NAV3 gene, mutation of NOC3L gene, mutation of PIK3C2A gene, mutation of SCUBE2 gene, mutation of SLC45A1 gene, mutation of TBC1D9 gene and mutation of ZNF282 gene It may be at least one selected from the group.

The method of providing information necessary for prognostic diagnosis of the bladder cancer patient may predict the total survival rate or disease-free survival rate of the bladder cancer patient. For example, the method may include, when the survival-specific marker is identified, determining that the survival rate is lower than that of a person whose survival-specific marker is not identified. Or vice versa.

In addition, the method may include, when the survival-specific marker is identified, determining that the recurrence rate of bladder cancer is higher than that of a person for which the survival-specific marker is not identified. Or vice versa.

For example, among the survival-specific markers, at least one selected from the group consisting of a mutation of the ASIC5 gene, a mutation of the DCAF4 gene, a mutation of the EPAS1 gene, a mutation of the NME9 gene, a mutation of the NRXN3 gene, and a mutation of the ZNF282 gene is confirmed In this case, it can be determined that the survival rate is lower or the recurrence rate is higher than that of a person for which the survival-specific marker is not identified.

In addition, among the survival-specific markers, CTNND1 gene mutation, EPS15L1 gene mutation, FBN2 gene mutation, GLDC gene mutation, GRIA2 gene mutation, GUCY1A2 gene mutation, ITGA3 gene mutation, ITGA4 gene mutation, KIF19 gene mutation, KIF1B gene mutation, MAATS1 gene mutation, MCM8 gene mutation, MCTP1 gene mutation, MED1 gene mutation, MTUS2 gene mutation, NAV3 gene mutation, NOC3L gene mutation, PIK3C2A gene mutation, POLK gene mutation in PRKG2 gene, mutation in RIN3 gene, mutation in SCUBE2 gene, mutation in SLC45A1 gene, mutation in SORL2 gene, mutation in SP4 gene, mutation in TBC1D9 gene, mutation in TEK gene, mutation in TMC1 gene, mutation in TNS3 gene When at least one selected from the group consisting of mutation, TRPM3 gene mutation, TXK gene mutation, UNC13D gene mutation, and ZNF207 gene mutation is identified, the survival rate is higher than that of a person whose survival-specific marker is not identified, or It can be concluded that the recurrence rate is low.

As such, the mutants of the genes of the present invention are A2ML1, ANAPC1, ARNT2, ASIC5, BIRC6, BTBD10, EDRF1, CFHR4, CLHC1, CTNND1, DCAF4, DHX37, EPAS1, FBN2, GLDC, GRIA2, GUCY1A2, ITGA3, ITGA4, KIF3 KIF1B, LPIN1, MAATS1, MCM8, MCTP1, MED1, MTUS2, NAV3, NME9, NOC3L, NRXN3, PIK3C2A, POLK, PRKG2, RIN3, SCUBE2, SLC45A1, SORL1, SP4, TBC3, TXK, TEK, TBC1D9, TEK It has not yet been revealed that the recurrence or prognosis for bladder cancer can be diagnosed using a mutation of at least one gene selected from the gene group consisting of UNC13D, ZNF207 and ZNF282. In addition, it has not been reported that the total survival rate or disease-free survival rate may be different for each gene. The present inventors have identified for the first time that mutations of the above genes can be used as diagnostic markers for predicting differences in therapeutic effects of bladder cancer patients or diagnosing the prognosis of bladder cancer patients.

The method of providing information necessary for predicting the difference in the treatment effect of bladder cancer patients of the present invention can be used to diagnose a bladder cancer gene mutation, increase the survival rate of bladder cancer patients, or lower the recurrence rate. Through the method for prognostic diagnosis of bladder cancer patients of the present invention, it is possible to predict the treatment effect of bladder cancer patients, or the survival rate or recurrence rate of bladder cancer patients by using the mutational information of the bladder cancer gene, so finding a therapeutic agent suitable for each patient In addition, it can provide information on the selection of treatments, so that a therapeutic strategy for bladder cancer can be efficiently designed.

Hereinafter, the present invention will be described in detail by way of Examples and Experimental Examples.

However, the following Examples and Experimental Examples are only for illustrating the present invention, and the content of the present invention is not limited by the following Examples and Experimental Examples.

Example

Securing genetic and clinical information

In order to derive a survival-specific marker for diagnosing the prognosis of bladder cancer, data on recurrence, metastasis, death, observation time, etc. of 411 bladder cancer patients who have both genetic and clinical information from TCGA (The Cancer Genome Atlas) was obtained and used for analysis. Table 1 below shows data on the gender and survival of bladder cancer patients.

number of patients ratio(%) gender male 303 73.7 female 108 26.3 survival O 230 56.0 X 181 44.0 Sum 411 100

Selection of genes relevant to survival

For the data of the 411 people, divided into two groups of survival (S0)/death (S1) according to the presence or absence of survival, and machine learning was performed with three Feature Selection (Information Gain, Chi-Square, MR) methods, The following 69 genes were derived that were survival-related:

A2ML1, ACAN, AGAP6, ANAPC1, ARNT2, ASIC5, BIRC6, BTBD10, EDRF1, CACNA1B, CFHR4, CLHC1, CTNND1, DCAF4, DDX46, DHX37, EPAS1, EPS15L1, FBN2, ITGA3GRIA2, GL DC, ITGA3, GRIA2, GL ITGA4, KIF19, KIF1B, LBR, LPIN1, MAATS1, MCM8, MCTP1, MED1, MSH6, MTUS2, NAV3, NCOR1, NME9, NOC3L, NRXN3, PHLPP2, PIK3C2A, POLK, PRKG1, SCUBE2, PRKG1, SCUBE2, PRKG1, PSG9B SORL1, SP4, SPAG9, ST6GALNAC5, TBC1D9, TEK, TEX26, TMC1, TNS3, TRIP12, TRIT1, TRPM3, TTF2, TXK, UNC13D, ZNF207, ZNF282, ZNF483, ZSCAN1.

Screening and review of survival-specific markers for prognosis

The present inventors performed comparative analysis on the data of the 411 subjects in order to confirm the applicability as a survival-specific marker for 69 genes related to survival, missing values, specificity values were excluded.

Based on the clinical information (event (death or recurrence), observation time) of the patients, overall survival or disease-free survival was calculated by Kaplan Meier survival analysis using SPSS. In the total survival period, the event was defined as death, and in the disease-free survival period, the event was defined as bladder cancer recurrence. In order to determine whether mutation in each of the genes is correlated with bladder cancer-caused death or bladder cancer recurrence, mutation occurrence and total survival were based on the event time of each group obtained in the Kaplan Meier survival assay. The association of duration, and association of mutagenesis and disease-free survival, was confirmed by log rank test. A p-value of less than 0.05 was considered statistically significant.

The experimental group was defined as the case with alterations in query gene, and the control group was the case without alterations in query gene. The median months survival means a value located at the center when the survival periods of patients in the corresponding group are listed. The slope in the survival curve by the Kaplan Meier survival assay is determined by the duration of survival. The p values of the analysis results are specifically shown in Table 2 below.

number of mutations Mutation (%) Cyto band Mutation type Total survival (p-value) Disease-free survival (p-value) cut missense in-frame A2ML1 12 2.9% 12p13.31 One 11 0 0.0133 0.453 ACAN 24 5.8% 15q26.1 One 23 0 0.145 0.216 AGAP6 4 1.0% 10q11.23 0 4 0 0.0682 0.131 ANAPC1 19 4.6% 2q13 5 14 0 0.00364 0.0373 ARNT2 11 2.7% 15q25.1 0 10 0 0.0227 0.0692 ASIC5 9 2.2% 4q32.1 One 8 0 0.00889 0.0811 BIRC6 74 17.9% 2p22.3 4 70 0 0.00327 0.0616 BTBD10 8 1.9% 11p15.3 0 8 0 0.0344 0.0282 EDRF1 11 2.7% 10q26.2 0 11 0 0.0191 0.0526 CACNA1B 17 4.1% 9q34.3 One 16 0 0.174 0.24 CFHR4 13 3.1% 1q31.3 2 11 0 0.0323 0.414 CLHC1 10 2.4% 2p16.1 One 9 0 0.0146 0.768 CTNND1 10 2.4% 11q12.1 4 6 0 0.00695 0.424 DCAF4 3 0.7% 14q24.2 One 2 0 0.0542 0.0206 DDX46 12 2.9% 5q31.1 0 12 0 0.0729 0.915 DHX37 7 1.7% 12q24.31 One 6 0 0.0329 0.0333 EPAS1 4 1.0% 2p21 0 4 0 0.0278 0.169 EPS15L1 7 1.7% 19p13.11 One 6 0 0.0639 0.799 FBN2 35 8.5% 5q23.3 6 28 One 0.0039 0.194 FZD3 6 1.5% 8p21.1 One 5 0 0.0958 0.533 GLDC 8 1.9% 9p24.1 One 7 0 0.0173 0.422 GRIA2 9 2.2% 4q32.1 0 9 0 0.014 0.0418 GRIK3 15 3.6% 1p34.3 3 12 0 0.221 0.203 GUCY1A2 13 3.1% 11q22.3 2 10 One 0.0209 0.0181 ITGA3 10 2.4% 17q21.33 One 6 0 0.00799 0.0071 ITGA4 20 4.8% 2q31.3 4 16 0 0.00241 0.353 KIF19 10 2.4% 17q25.1 2 8 0 0.00947 0.0252 KIF1B 18 4.4% 1p36.22 4 14 0 0.0117 0.00997 LBR 7 1.7% 1q42.12 0 6 0 0.206 0.504 LPIN1 7 1.7% 2p25.1 0 7 0 0.0369 0.334 MAATS1 8 1.9% 3q13.33 2 6 0 0.0438 0.0442 MCM8 12 2.9% 20p12.3 0 12 0 0.0189 0.0797 MCTP1 12 2.9% 5q15 One 11 0 0.0108 0.263 MED1 21 5.1% 17q12 3 18 0 0.005 0.0154 MSH6 11 2.7% 2p16.3 2 8 One 0.0632 0.201 MTUS2 14 3.4% 13q12.3 One 12 One 0.0436 0.0367 NAV3 31 7.5% 12q21.2 2 29 0 0.00235 0.0266 NCOR1 44 10.7% 17p12-p11.2 15 29 0 0.0714 0.146 NME9 5 1.2% 3q22.3 0 5 0 0.0381 0.25 NOC3L 11 2.7% 10q23.33 0 11 0 0.0105 0.0292 NRXN3 10 2.4% 14q24.3-q31.1 One 9 0 9.01E-04 0.0796 PHLP2 10 2.4% 16q22.2 0 10 0 0.0614 0.193 PIK3C2A 18 4.4% 11p15.1 4 14 0 0.00168 0.00475 POLK 13 3.1% 5q13.3 0 12 0 0.00985 0.439 PRKG2 9 2.2% 4q21.21 One 8 0 0.0186 0.145 PSG4 7 1.7% 19q13.31 One 5 0 0.36 0.449 RIN3 9 2.2% 14q32.12 One 8 0 0.0287 0.0809 SCUBE2 9 2.2% 11p15.4 One 8 0 0.0234 0.0282 SLC45A1 11 2.7% 1p36.23 One 10 0 0.0165 0.0425 SLC9B1 7 1.7% 4q24 One 6 0 0.0672 0.516 SORL1 15 3.6% 11q24.1 7 8 0 0.0147 0.137 SP4 9 2.2% 7p15.3 0 9 0 0.0226 0.0733 SPAG9 9 2.2% 17q21.33 One 8 0 0.125 0.211 ST6GALNAC5 4 1.0% 1p31.1 0 4 0 0.0827 0.0901 TBC1D9 8 1.9% 4q31.21 0 8 0 0.0312 0.0306 TEK 10 2.4% 9p21.2 0 10 0 0.0294 0.56 TEX26 8 1.9% 13q12.3 2 6 0 0.176 0.383 TMC1 7 1.7% 9q21.13 0 7 0 0.0401 0.127 TNS3 15 3.6% 7p12.3 One 14 0 0.0157 0.65 TRIP12 13 3.1% 2q36.3 5 8 0 0.0979 0.162 TRIT1 8 1.9% 1p34.2 0 8 0 0.131 0.127 TRPM3 23 5.6% 9q21.12-q21.13 2 21 0 0.0207 0.236 TTF2 11 2.7% 1p13.1 3 8 0 0.129 0.106 TXK 11 2.7% 4p12 3 8 0 0.0416 0.125 UNC13D 10 2.4% 17q25.1 One 9 0 0.0244 0.0687 ZNF207 9 2.2% 17q11.2 0 9 0 0.0484 0.373 ZNF282 7 1.7% 7q36.1 0 7 0 8.02E-06 8.12E-06 ZNF483 11 2.7% 9q31.3 2 9 0 0.0611 0.171 ZSCAN1 6 1.5% 19q13.43 One 5 0 0.521 0.204

Among the genes in Table 2, the following 21 genes have p values of overall survival and disease-free survival of 0.05 or more, and it is judged that the correlation with total survival or recurrence is low:

ACAN, AGAP6, CACNA1B, DDX46, EPS15L1, FZD3, GRIK3, LBR, MSH6, NCOR1, PHLPP2, PSG4, SLC9B1, SPAG9, ST6GALNAC5, TEX26, TRIP12, TRIT1, TTF2, ZSCAN1.

In addition, the following 48 genes (candidate gene group 1) have a p-value of less than 0.05 for total survival or disease-free survival, and are considered genes highly correlated with survival or recurrence. It is judged to be low or the recurrence rate is high.

Candidate gene group 1: A2ML1, ANAPC1, ARNT2, ASIC5, BIRC6, BTBD10, EDRF1, CFHR4, CLHC1, CTNND1, DCAF4, DHX37, EPAS1, FBN2, GLDC, GRIA2, GUCY1A2, LPIN1, ITGA4, KIF19, ITGA4 MAATS1, MCM8, MCTP1, MED1, MTUS2, NAV3, NME9, NOC3L, NRXN3, PIK3C2A, POLK, PRKG2, RIN3, SCUBE2, SLC45A1, SORL1, SP4, TBC1D9, TEK, TBC1D9, TEK, TBC13DMC1, ZNF3, TNS3, TRPM ZNF282.

Table 3 below shows the results of Kaplan Meier analysis of 47 genes having a p-value of less than 0.05 in total survival among the first group of candidate genes.

Total survival (p-value) no mutation with mutation Total number of people (persons) Number of deaths (persons) death rate(%) Median survival time
(month) Total number of people (persons) Number of deaths (persons) death rate(%) Median survival time
(month) A2ML1 0.0133 397 178 44.84 33.02 12 One 8.33 NA ANAPC1 0.00364 393 178 45.29 32.98 16 One 6.25 NA ARNT2 0.0227 400 179 44.75 33.02 9 0 0 NA ASIC5 0.00889 401 179 44.64 33.02 8 0 0 NA BIRC6 0.00327 358 167 46.65 31.18 51 12 23.53 NA BTBD10 0.0344 401 179 44.64 33.02 8 0 0 NA C10orf137 0.0191 398 179 44.97 33.02 11 0 0 NA CFHR4 0.0323 397 177 44.58 33.02 12 2 16.67 NA CLHC1 0.0146 399 179 44.86 33.02 10 0 0 NA CTNND1 0.00695 399 179 44.86 32.98 10 0 0 NA DHX37 0.0329 402 179 44.53 33.11 7 0 0 NA EPAS1 0.0278 405 175 43.21 34.95 4 4 100 5.35 FBN2 0.0039 379 173 45.65 32 30 6 20 NA GLDC 0.0173 401 179 44.64 33.02 8 0 0 NA GRIA2 0.014 400 179 44.75 33.02 9 0 0 NA GUCY1A2 0.0209 396 178 44.95 33.02 13 One 7.69 NA ITGA3 0.00799 399 179 44.86 33.02 10 0 0 NA ITGA4 0.00241 392 177 45.15 32 17 2 11.76 NA KIF19 0.00947 400 179 44.75 33.02 9 0 0 NA KIF1B 0.0117 392 177 45.15 32.98 17 2 11.76 NA LPIN1 0.0369 402 179 44.53 33.11 7 0 0 NA MAATS1 0.0438 401 178 44.39 33.11 8 One 12.5 NA MCM8 0.0189 400 178 44.5 33.02 9 One 11.11 NA MCTP1 0.0108 397 179 45.09 33.02 12 0 0 NA MED1 0.005 392 177 45.15 32.98 17 2 11.76 NA MTUS2 0.0436 400 179 44.75 33.11 9 0 0 NA NAV3 0.00235 381 173 45.41 31.18 28 6 21.43 NA NME9 0.0381 404 174 43.07 34.95 5 5 100 13.14 NOC3L 0.0105 398 179 44.97 33.02 11 0 0 NA NRXN3 0.000901 399 170 42.61 35.38 10 9 90 8.97 PIK3C2A 0.00168 393 179 45.55 32.98 16 0 0 NA POLK 0.00985 397 179 45.09 33.02 12 0 0 NA PRKG2 0.0186 400 179 44.75 33.02 9 0 0 NA RIN3 0.0287 401 179 44.64 33.02 8 0 0 NA SCUBE2 0.0234 400 178 44.5 33.02 9 One 11.11 NA SLC45A1 0.0165 398 179 44.97 33.02 11 0 0 NA SORL1 0.0147 395 178 45.06 33.02 14 One 7.14 NA SP4 0.0226 401 179 44.64 33.02 8 0 0 NA TBC1D9 0.0312 401 178 44.39 33.02 8 One 12.5 NA TEK 0.0294 401 179 44.64 33.02 8 0 0 NA TMC1 0.0401 402 179 44.53 33.11 7 0 0 NA TNS3 0.0157 395 177 44.81 32.98 14 2 14.29 NA TRPM3 0.0207 390 176 45.13 32.98 19 3 15.79 NA TXK 0.0416 400 179 44.75 33.11 9 0 0 NA UNC13D 0.0244 399 179 44.86 33.02 10 0 0 NA ZNF207 0.0484 400 179 44.75 33.11 9 0 0 NA ZNF282 8.02E-06 403 173 42.93 35.38 6 6 100 8.34

In addition, the results of Kaplan Meier analysis for 19 genes having a p-value of less than 0.05 for disease-free survival are shown in Table 4 below.

Disease-free survival (p-value) no mutation with mutation Total number of people (persons) Number of recurrences (persons) Relapse rate (%) Median disease-free survival (months) Total number of people (persons) Number of recurrences (persons) Relapse rate (%) Median disease-free survival (months) ANAPC1 0.0373 307 140 45.6 29.89 15 3 20 NA BTBD10 0.0282 314 143 45.54 29.89 8 0 0 NA DCAF4 0.0206 321 142 44.24 30.22 One One 100 6.93 DHX37 0.0333 315 143 45.4 29.89 7 0 0 NA GRIA2 0.0418 313 142 45.37 29.8 9 One 11.11 NA GUCY1A2 0.0181 309 142 45.95 29.89 13 One 7.69 NA ITGA3 0.0071 312 143 45.83 29.8 10 0 0 NA KIF19 0.0252 313 142 45.37 29.89 9 One 11.11 NA KIF1B 0.00997 306 141 46.08 29.8 16 2 12.5 NA MAATS1 0.0442 314 142 45.22 29.89 8 One 12.5 NA MED1 0.0154 305 140 45.9 29.8 17 3 17.65 NA MTUS2 0.0367 313 143 45.69 29.89 9 0 0 NA NAV3 0.0266 296 135 45.61 29.47 26 8 30.77 NA NOC3L 0.0292 311 142 45.66 29.89 11 One 9.09 NA PIK3C2A 0.00475 306 142 46.41 29.8 16 One 6.25 NA SCUBE2 0.0282 314 142 45.22 29.8 8 One 12.5 NA SLC45A1 0.0425 311 142 45.66 29.89 11 One 9.09 NA TBC1D9 0.0306 315 142 45.08 29.89 7 One 14.29 NA ZNF282 8.12E-06 320 141 44.06 30.22 2 2 100 3.25

Also, among the first group of candidate genes, if there were mutations in the following 18 genes (candidate gene group 2), the survival rate was low, and the recurrence rate of bladder cancer was high or the disease-free survival period was short.

Candidate gene group 2: ANAPC1, BTBD10, DHX37, GRIA2, GUCY1A2, ITGA3, KIF19, KIF1B, MAATS1, MED1, MTUS2, NAV3, NOC3L, PIK3C2A, SCUBE2, SLC45A1, TBC1D9, ZNF282.

Detection of marker genes using mutation position information

Mutation position information of the candidate gene group 1 gene is shown below.

Gene AA change Type Copy # COSMIC Chr Start Pos End Pos HGVSc A2ML1 R807H Missense gain 4 chr12 9004565 9004565 ENST00000299698.7:c.2420G>A E222K Missense shallowdel One chr12 8988871 8988871 ENST00000299698.7:c.664G>A P1341Q Missense diploid 2 chr12 9020914 9020914 ENST00000299698.7:c.4022C>A Q1305* Nonsense diploid One chr12 9020633 9020633 ENST00000299698.7:c.3913C>T P176S Missense shallowdel One chr12 8988145 8988145 ENST00000299698.7:c.526C>T E202K Missense diploid One chr12 8988223 8988223 ENST00000299698.7:c.604G>A L522R Missense diploid chr12 8998700 8998700 ENST00000299698.7:c.1565T>G T1312M Missense diploid chr12 9020827 9020827 ENST00000299698.7:c.3935C>T P1377A Missense gain 2 chr12 9021200 9021200 ENST00000299698.7:c.4129C>G L1124F Missense gain chr12 9013761 9013761 ENST00000299698.7:c.3370C>T W763S Missense diploid chr12 9004433 9004433 ENST00000299698.7:c.2288G>C S718L Missense shallowdel chr12 9002789 9002789 ENST00000299698.7:c.2153C>T ANAPC1 S736L Missense gain One chr2 112592358 112592358 ENST00000341068.3:c.2207C>T S1530L Missense gain One chr2 112550062 112550062 ENST00000341068.3:c.4589C>T S341L Missense gain One chr2 112621282 112621282 ENST00000341068.3:c.1022C>T Q846P Missense gain One chr2 112588951 112588951 ENST00000341068.3:c.2537A>C L1662I Missense gain One chr2 112541911 112541911 ENST00000341068.3:c.4984C>A Y583* Nonsense gain chr2 112605344 112605344 ENST00000341068.3:c.1749C>A L1657F Missense diploid chr2 112541926 112541926 ENST00000341068.3:c.4969C>T K798T Missense diploid chr2 112590880 112590880 ENST00000341068.3:c.2393A>C D568G Missense diploid One chr2 112605390 112605390 ENST00000341068.3:c.1703A>G S156I Missense diploid chr2 112630946 112630946 ENST00000341068.3:c.467G>T L271V Missense gain chr2 112622403 112622403 ENST00000341068.3:c.811C>G Q846* Nonsense gain chr2 112588952 112588952 ENST00000341068.3:c.2536C>T Q827* Nonsense gain chr2 112589009 112589009 ENST00000341068.3:c.2479C>T K1066Rfs*17 Frame_Shift_Del diploid chr2 112578825 112578825 ENST00000341068.3:c.3197del E146Q Missense diploid chr2 112630977 112630977 ENST00000341068.3:c.436G>C T1264Qfs*14 Frame_Shift_Del shallowdel chr2 112566567 112566567 ENST00000341068.3:c.3789del R527W Missense diploid chr2 112608424 112608424 ENST00000341068.3:c.1579C>T S470L Missense diploid chr2 112614413 112614413 ENST00000341068.3:c.1409C>T M934I Missense diploid chr2 112582553 112582553 ENST00000341068.3:c.2802G>A ARNT2 D344G Missense shallowdel 2 chr15 80845057 80845057 ENST00000303329.4:c.1031A>G S654L Missense diploid One chr15 80883951 80883951 ENST00000303329.4:c.1961C>T T575A Missense diploid chr15 80872861 80872861 ENST00000303329.4:c.1723A>G L366V Missense gain chr15 80847412 80847412 ENST00000303329.4:c.1096C>G D549N Missense diploid chr15 80872783 80872783 ENST00000303329.4:c.1645G>A E193K Missense diploid chr15 80767519 80767519 ENST00000303329.4:c.577G>A A127T Missense diploid chr15 80762743 80762743 ENST00000303329.4:c.379G>A E137K Missense shallowdel chr15 80767351 80767351 ENST00000303329.4:c.409G>A M294I Missense diploid chr15 80843544 80843544 ENST00000303329.4:c.882G>A Q571H Missense diploid chr15 80872851 80872851 ENST00000303329.4:c.1713G>T ASIC5 P31A Missense amp chr4 156784856 156784856 ENST00000537611.2:c.91C>G Q305K Missense shallowdel chr4 156763455 156763455 ENST00000537611.2:c.913C>A P294H Missense diploid chr4 156763487 156763487 ENST00000537611.2:c.881C>A L64F Missense diploid chr4 156784757 156784757 ENST00000537611.2:c.190C>T P491A Missense gain chr4 156751055 156751055 ENST00000537611.2:c.1471C>G Y472* Nonsense gain chr4 156751110 156751110 ENST00000537611.2:c.1416C>G P490R Missense diploid chr4 156751057 156751057 ENST00000537611.2:c.1469C>G D250N Missense diploid chr4 156764946 156764946 ENST00000537611.2:c.748G>A H323Y Missense gain chr4 156763401 156763401 ENST00000537611.2:c.967C>T BIRC6 S464L Missense amp chr2 32626664 32626664 ENST00000421745.2:c.1391C>T S4205L Missense gain 2 chr2 32770731 32770731 ENST00000421745.2:c.12614C>T R1789I Missense shallowdel 2 chr2 32692602 32692602 ENST00000421745.2:c.5366G>T R4400W Missense diploid One chr2 32800276 32800276 ENST00000421745.2:c.13198C>T R4732* Nonsense gain 2 chr2 32832645 32832645 ENST00000421745.2:c.14194C>T E1723K Missense gain One chr2 32689802 32689802 ENST00000421745.2:c.5167G>A P2756R Missense gain One chr2 32716552 32716552 ENST00000421745.2:c.8267C>G L2766V Missense diploid One chr2 32716581 32716581 ENST00000421745.2:c.8296C>G D3628H Missense diploid One chr2 32740370 32740370 ENST00000421745.2:c.10882G>C A3599T Missense gain 2 chr2 32740283 32740283 ENST00000421745.2:c.10795G>A S1500N Missense gain One chr2 32673877 32673877 ENST00000421745.2:c.4499G>A E755K Missense gain 2 chr2 32640622 32640622 ENST00000421745.2:c.2263G>A Q3827* Nonsense gain One chr2 32743450 32743450 ENST00000421745.2:c.11479C>T S321C Missense diploid One chr2 32620589 32620589 ENST00000421745.2:c.962C>G L1566V Missense diploid One chr2 32678953 32678953 ENST00000421745.2:c.4696C>G N2735H Missense shallowdel One chr2 32715215 32715215 ENST00000421745.2:c.8203A>C D448N Missense gain One chr2 32626615 32626615 ENST00000421745.2:c.1342G>A M418I Missense diploid One chr2 32626450 32626450 ENST00000421745.2:c.1254G>A M3472I Missense diploid One chr2 32738069 32738069 ENST00000421745.2:c.10416G>T R4713L Missense diploid One chr2 32832589 32832589 ENST00000421745.2:c.14138G>T R4713L Missense diploid One chr2 32832589 32832589 ENST00000421745.2:c.14138G>T D1418Y Missense gain One chr2 32668572 32668572 ENST00000421745.2:c.4252G>T G1465E Missense gain One chr2 32670646 32670646 ENST00000421745.2:c.4394G>A D1504N Missense gain One chr2 32673888 32673888 ENST00000421745.2:c.4510G>A L3858F Missense gain One chr2 32743962 32743962 ENST00000421745.2:c.11572C>T H3859Y Missense gain One chr2 32743965 32743965 ENST00000421745.2:c.11575C>T L3870V Missense gain One chr2 32743998 32743998 ENST00000421745.2:c.11608C>G L3768V Missense gain One chr2 32740790 32740790 ENST00000421745.2:c.11302C>G E1825Q Missense shallowdel One chr2 32692709 32692709 ENST00000421745.2:c.5473G>C S2862L Missense diploid chr2 32724730 32724730 ENST00000421745.2:c.8585C>T Q317E Missense gain One chr2 32617216 32617216 ENST00000421745.2:c.949C>G H3493N Missense gain One chr2 32738130 32738130 ENST00000421745.2:c.10477C>A S461C Missense amp chr2 32626655 32626655 ENST00000421745.2:c.1382C>G G3485V Missense gain One chr2 32738107 32738107 ENST00000421745.2:c.10454G>T G3485S Missense gain One chr2 32738106 32738106 ENST00000421745.2:c.10453G>A K3894T Missense diploid chr2 32750012 32750012 ENST00000421745.2:c.11681A>C S440L Missense diploid chr2 32626592 32626592 ENST00000421745.2:c.1319C>T D1803N Missense shallowdel chr2 32692643 32692643 ENST00000421745.2:c.5407G>A Q4108E Missense gain chr2 32768338 32768338 ENST00000421745.2:c.12322C>G Q4634E Missense diploid chr2 32824875 32824875 ENST00000421745.2:c.13900C>G S4593L Missense diploid chr2 32822983 32822983 ENST00000421745.2:c.13778C>T S4592F Missense diploid chr2 32822980 32822980 ENST00000421745.2:c.13775C>T M3052I Missense diploid One chr2 32726904 32726904 ENST00000421745.2:c.9156G>C T3988A Missense gain chr2 32754759 32754759 ENST00000421745.2:c.11962A>G E3242K Missense gain chr2 32733070 32733070 ENST00000421745.2:c.9724G>A S2883L Missense gain chr2 32724793 32724793 ENST00000421745.2:c.8648C>T V3693Yfs*10 Frame_Shift_Del gain chr2 32740564 32740577 ENST00000421745.2:c.11077_11090del E4428Q Missense diploid chr2 32800360 32800360 ENST00000421745.2:c.13282G>C L2358F Missense diploid chr2 32703706 32703706 ENST00000421745.2:c.7072C>T S3504G Missense diploid One chr2 32738163 32738163 ENST00000421745.2:c.10510A>G D4822N Missense diploid chr2 32842861 32842861 ENST00000421745.2:c.14464G>A L2508V Missense diploid One chr2 32706501 32706501 ENST00000421745.2:c.7522C>G E4486Q Missense gain chr2 32819082 32819082 ENST00000421745.2:c.13456G>C E4826* Nonsense diploid chr2 32842873 32842873 ENST00000421745.2:c.14476G>T P2609L Missense diploid chr2 32712726 32712726 ENST00000421745.2:c.7826C>T L4689M Missense gain chr2 32828145 32828145 ENST00000421745.2:c.14065T>A S3740L Missense gain chr2 32740707 32740707 ENST00000421745.2:c.11219C>T W2403C Missense diploid chr2 32703843 32703843 ENST00000421745.2:c.7209G>C L4698R Missense diploid chr2 32832544 32832544 ENST00000421745.2:c.14093T>G S480L Missense diploid chr2 32631587 32631587 ENST00000421745.2:c.1439C>T E164G Missense diploid chr2 32602821 32602821 ENST00000421745.2:c.491A>G D2414H Missense diploid chr2 32703874 32703874 ENST00000421745.2:c.7240G>C S4586L Missense shallowdel chr2 32822962 32822962 ENST00000421745.2:c.13757C>T L4612V Missense shallowdel chr2 32824809 32824809 ENST00000421745.2:c.13834C>G Q1060E Missense diploid chr2 32656088 32656088 ENST00000421745.2:c.3178C>G R276G Missense diploid 2 chr2 32613998 32613998 ENST00000421745.2:c.826C>G E499K Missense gain chr2 32639854 32639854 ENST00000421745.2:c.1495G>A S581L Missense gain chr2 32640101 32640101 ENST00000421745.2:c.1742C>T L1703F Missense gain chr2 32689742 32689742 ENST00000421745.2:c.5107C>T L632F Missense diploid chr2 32640253 32640253 ENST00000421745.2:c.1894C>T E2861K Missense shallowdel One chr2 32724726 32724726 ENST00000421745.2:c.8581G>A L3214F Missense diploid chr2 32730212 32730212 ENST00000421745.2:c.9640C>T L4239S Missense gain chr2 32770833 32770833 ENST00000421745.2:c.12716T>C M3347I Missense diploid chr2 32734865 32734865 ENST00000421745.2:c.10041G>C

Based on the mutation position information, it is possible to manufacture a microchip using a primer, a probe, an antibody, or an aptamer capable of detecting the marker gene, and the specific method may be according to a conventional technique.

In the above, preferred embodiments of the present invention have been exemplarily described, but the scope of the present invention is not limited to the specific embodiments as described above, and those of ordinary skill in the art will It can be appropriately changed within.

<110> THE CATHOLIC UNIVERSITY OF KOREA INDUSTRY-ACADEMIC COOPERATION FOUNDATION <120> Composition And Kit For Diagnosing Prognosis Of Bladder Cancer <130> 2021-DPA-4423D <150> KR 10-2020-0037738 <151> 2020-03-27 <160> 48 <170> KoPatentIn 3.0 <210> 1 <211> 1454 <212> PRT <213> Homo sapiens <400> 1 Met Trp Ala Gln Leu Leu Leu Gly Met Leu Ala Leu Ser Pro Ala Ile 1 5 10 15 Ala Glu Glu Leu Pro Asn Tyr Leu Val Thr Leu Pro Ala Arg Leu Asn 20 25 30 Phe Pro Ser Val Gln Lys Val Cys Leu Asp Leu Ser Pro Gly Tyr Ser 35 40 45 Asp Val Lys Phe Thr Val Thr Leu Glu Thr Lys Asp Lys Thr Gln Lys 50 55 60 Leu Leu Glu Tyr Ser Gly Leu Lys Lys Arg His Leu His Cys Ile Ser 65 70 75 80 Phe Leu Val Pro Pro Ala Gly Gly Thr Glu Glu Val Ala Thr Ile 85 90 95 Arg Val Ser Gly Val Gly Asn Asn Ile Ser Phe Glu Glu Lys Lys Lys 100 105 110 Val Leu Ile Gln Arg Gln Gly Asn Gly Thr Phe Val Gln Thr Asp Lys 115 120 125 Pro Leu Tyr Thr Pro Gly Gln Gln Val Tyr Phe Arg Ile Val Thr Met 130 135 140 Asp Ser Asn Phe Val Pro Val Asn Asp Lys Tyr Ser Met Val Glu Leu 145 150 155 160 Gln Asp Pro Asn Ser Asn Arg Ile Ala Gln Trp Leu Glu Val Val Pro 165 170 175 Glu Gln Gly Ile Val Asp Leu Ser Phe Gln Leu Ala Pro Glu Ala Met 180 185 190 Leu Gly Thr Tyr Thr Val Ala Val Ala Glu Gly Lys Thr Phe Gly Thr 195 200 205 Phe Ser Val Glu Glu Tyr Val Leu Pro Lys Phe Lys Val Glu Val Val 210 215 220 Glu Pro Lys Glu Leu Ser Thr Val Gln Glu Ser Phe Leu Val Lys Ile 225 230 235 240 Cys Cys Arg Tyr Thr Tyr Gly Lys Pro Met Leu Gly Ala Val Gln Val 245 250 255 Ser Val Cys Gln Lys Ala Asn Thr Tyr Trp Tyr Arg Glu Val Glu Arg 260 265 270 Glu Gln Leu Pro Asp Lys Cys Arg Asn Leu Ser Gly Gln Thr Asp Lys 275 280 285 Thr Gly Cys Phe Ser Ala Pro Val Asp Met Ala Thr Phe Asp Leu Ile 290 295 300 Gly Tyr Ala Tyr Ser His Gln Ile Asn Ile Val Ala Thr Val Val Glu 305 310 315 320 Glu Gly Thr Gly Val Glu Ala Asn Ala Thr Gln Asn Ile Tyr Ile Ser 325 330 335 Pro Gln Met Gly Ser Met Thr Phe Glu Asp Thr Ser Asn Phe Tyr His 340 345 350 Pro Asn Phe Pro Phe Ser Gly Lys Ile Arg Val Arg Gly His Asp Asp 355 360 365 Ser Phe Leu Lys Asn His Leu Val Phe Leu Val Ile Tyr Gly Thr Asn 370 375 380 Gly Thr Phe Asn Gln Thr Leu Val Thr Asp Asn Asn Gly Leu Ala Pro 385 390 395 400 Phe Thr Leu Glu Thr Ser Gly Trp Asn Gly Thr Asp Val Ser Leu Glu 405 410 415 Gly Lys Phe Gln Met Glu Asp Leu Val Tyr Asn Pro Glu Gln Val Pro 420 425 430 Arg Tyr Tyr Gln Asn Ala Tyr Leu His Leu Arg Pro Phe Tyr Ser Thr 435 440 445 Thr Arg Ser Phe Leu Gly Ile His Arg Leu Asn Gly Pro Leu Lys Cys 450 455 460 Gly Gln Pro Gln Glu Val Leu Val Asp Tyr Tyr Ile Asp Pro Ala Asp 465 470 475 480 Ala Ser Pro Asp Gln Glu Ile Ser Phe Ser Tyr Tyr Leu Ile Gly Lys 485 490 495 Gly Ser Leu Val Met Glu Gly Gln Lys His Leu Asn Ser Lys Lys Lys 500 505 510 Gly Leu Lys Ala Ser Phe Ser Leu Ser Leu Thr Phe Thr Ser Arg Leu 515 520 525 Ala Pro Asp Pro Ser Leu Val Ile Tyr Ala Ile Phe Pro Ser Gly Gly 530 535 540 Val Val Ala Asp Lys Ile Gln Phe Ser Val Glu Met Cys Phe Asp Asn 545 550 555 560 Gln Val Ser Leu Gly Phe Ser Pro Ser Gln Gln Leu Pro Gly Ala Glu 565 570 575 Val Glu Leu Gln Leu Gln Ala Ala Pro Gly Ser Leu Cys Ala Leu Arg 580 585 590 Ala Val Asp Glu Ser Val Leu Leu Leu Arg Pro Asp Arg Glu Leu Ser 595 600 605 Asn Arg Ser Val Tyr Gly Met Phe Pro Phe Trp Tyr Gly His Tyr Pro 610 615 620 Tyr Gln Val Ala Glu Tyr Asp Gln Cys Pro Val Ser Gly Pro Trp Asp 625 630 635 640 Phe Pro Gln Pro Leu Ile Asp Pro Met Pro Gln Gly His Ser Ser Gln 645 650 655 Arg Ser Ile Ile Trp Arg Pro Ser Phe Ser Glu Gly Thr Asp Leu Phe 660 665 670 Ser Phe Phe Arg Asp Val Gly Leu Lys Ile Leu Ser Asn Ala Lys Ile 675 680 685 Lys Lys Pro Val Asp Cys Ser His Arg Ser Pro Glu Tyr Ser Thr Ala 690 695 700 Met Gly Ala Gly Gly Gly His Pro Glu Ala Phe Glu Ser Ser Thr Pro 705 710 715 720 Leu His Gln Ala Glu Asp Ser Gln Val Arg Gln Tyr Phe Pro Glu Thr 725 730 735 Trp Leu Trp Asp Leu Phe Pro Ile Gly Asn Ser Gly Lys Glu Ala Val 740 745 750 His Val Thr Val Pro Asp Ala Ile Thr Glu Trp Lys Ala Met Ser Phe 755 760 765 Cys Thr Ser Gln Ser Arg Gly Phe Gly Leu Ser Pro Thr Val Gly Leu 770 775 780 Thr Ala Phe Lys Pro Phe Phe Val Asp Leu Thr Leu Pro Tyr Ser Val 785 790 795 800 Val Arg Gly Glu Ser Phe Arg Leu Thr Ala Thr Ile Phe Asn Tyr Leu 805 810 815 Lys Asp Cys Ile Arg Val Gln Thr Asp Leu Ala Lys Ser His Glu Tyr 820 825 830 Gln Leu Glu Ser Trp Ala Asp Ser Gln Thr Ser Ser Cys Leu Cys Ala 835 840 845 Asp Asp Ala Lys Thr His His Trp Asn Ile Thr Ala Val Lys Leu Gly 850 855 860 His Ile Asn Phe Thr Ile Ser Thr Lys Ile Leu Asp Ser Asn Glu Pro 865 870 875 880 Cys Gly Gly Gln Lys Gly Phe Val Pro Gln Lys Gly Arg Ser Asp Thr 885 890 895 Leu Ile Lys Pro Val Leu Val Lys Pro Glu Gly Val Leu Val Glu Lys 900 905 910 Thr His Ser Ser Leu Leu Cys Pro Lys Gly Lys Val Ala Ser Glu Ser 915 920 925 Val Ser Leu Glu Leu Pro Val Asp Ile Val Pro Asp Ser Thr Lys Ala 930 935 940 Tyr Val Thr Val Leu Gly Asp Ile Met Gly Thr Ala Leu Gln Asn Leu 945 950 955 960 Asp Gly Leu Val Gln Met Pro Ser Gly Cys Gly Glu Gln Asn Met Val 965 970 975 Leu Phe Ala Pro Ile Ile Tyr Val Leu Gln Tyr Leu Glu Lys Ala Gly 980 985 990 Leu Leu Thr Glu Glu Ile Arg Ser Arg Ala Val Gly Phe Leu Glu Ile 995 1000 1005 Gly Tyr Gln Lys Glu Leu Met Tyr Lys His Ser Asn Gly Ser Tyr Ser 1010 1015 1020 Ala Phe Gly Glu Arg Asp Gly Asn Gly Asn Thr Trp Leu Thr Ala Phe 1025 1030 1035 1040 Val Thr Lys Cys Phe Gly Gln Ala Gln Lys Phe Ile Phe Ile Asp Pro 1045 1050 1055 Lys Asn Ile Gln Asp Ala Leu Lys Trp Met Ala Gly Asn Gln Leu Pro 1060 1065 1070 Ser Gly Cys Tyr Ala Asn Val Gly Asn Leu Leu His Thr Ala Met Lys 1075 1080 1085 Gly Gly Val Asp Asp Glu Val Ser Leu Thr Ala Tyr Val Thr Ala Ala 1090 1095 1100 Leu Leu Glu Met Gly Lys Asp Val Asp Asp Pro Met Val Ser Gln Gly 1105 1110 1115 1120 Leu Arg Cys Leu Lys Asn Ser Ala Thr Ser Thr Thr Asn Leu Tyr Thr 1125 1130 1135 Gln Ala Leu Leu Ala Tyr Ile Phe Ser Leu Ala Gly Glu Met Asp Ile 1140 1145 1150 Arg Asn Ile Leu Leu Lys Gln Leu Asp Gln Gln Ala Ile Ile Ser Gly 1155 1160 1165 Glu Ser Ile Tyr Trp Ser Gln Lys Pro Thr Pro Ser Ser Asn Ala Ser 1170 1175 1180 Pro Trp Ser Glu Pro Ala Ala Val Asp Val Glu Leu Thr Ala Tyr Ala 1185 1190 1195 1200 Leu Leu Ala Gln Leu Thr Lys Pro Ser Leu Thr Gln Lys Glu Ile Ala 1205 1210 1215 Lys Ala Thr Ser Ile Val Ala Trp Leu Ala Lys Gln His Asn Ala Tyr 1220 1225 1230 Gly Gly Phe Ser Ser Thr Gln Asp Thr Val Val Ala Leu Gln Ala Leu 1235 1240 1245 Ala Lys Tyr Ala Thr Thr Ala Tyr Met Pro Ser Glu Glu Ile Asn Leu 1250 1255 1260 Val Val Lys Ser Thr Glu Asn Phe Gln Arg Thr Phe Asn Ile Gln Ser 1265 1270 1275 1280 Val Asn Arg Leu Val Phe Gln Gln Asp Thr Leu Pro Asn Val Pro Gly 1285 1290 1295 Met Tyr Thr Leu Glu Ala Ser Gly Gly Gly Cys Val Tyr Val Gln Thr 1300 1305 1310 Val Leu Arg Tyr Asn Ile Leu Pro Pro Thr Asn Met Lys Thr Phe Ser 1315 1320 1325 Leu Ser Val Glu Ile Gly Lys Ala Arg Cys Glu Gln Pro Thr Ser Pro 1330 1335 1340 Arg Ser Leu Thr Leu Thr Ile His Thr Ser Tyr Val Gly Ser Arg Ser 1345 1350 1355 1360 Ser Ser Asn Met Ala Ile Val Glu Val Lys Met Leu Ser Gly Phe Ser 1365 1370 1375 Pro Met Glu Gly Thr Asn Gln Leu Leu Leu Gln Gln Pro Leu Val Lys 1380 1385 1390 Lys Val Glu Phe Gly Thr Asp Thr Leu Asn Ile Tyr Leu Asp Glu Leu 1395 1400 1405 Ile Lys Asn Thr Gln Thr Tyr Thr Phe Thr Ile Ser Gln Ser Val Leu 1410 1415 1420 Val Thr Asn Leu Lys Pro Ala Thr Ile Lys Val Tyr Asp Tyr Tyr Leu 1425 1430 1435 1440 Pro Asp Glu Gln Ala Thr Ile Gln Tyr Ser Asp Pro Cys Glu 1445 1450 <210> 2 <211> 1944 <212> PRT <213> Homo sapiens <400> 2 Met Ser Asn Phe Tyr Glu Glu Arg Thr Thr Met Ile Ala Ala Arg Asp 1 5 10 15 Leu Gln Glu Phe Val Pro Phe Gly Arg Asp His Cys Lys His His Pro 20 25 30 Asn Ala Leu Asn Leu Gln Leu Arg Gln Leu Gln Pro Ala Ser Glu Leu 35 40 45 Trp Ser Ser Asp Gly Ala Ala Gly Leu Val Gly Ser Leu Gln Glu Val 50 55 60 Thr Ile His Glu Lys Gln Lys Glu Ser Trp Gln Leu Arg Lys Gly Val 65 70 75 80 Ser Glu Ile Gly Glu Asp Val Asp Tyr Asp Glu Glu Leu Tyr Val Ala 85 90 95 Gly Asn Met Val Ile Trp Ser Lys Gly Ser Lys Ser Gln Ala Leu Ala 100 105 110 Val Tyr Lys Ala Phe Thr Val Asp Ser Pro Val Gln Gln Ala Leu Trp 115 120 125 Cys Asp Phe Ile Ile Ser Gln Asp Lys Ser Glu Lys Ala Tyr Ser Ser 130 135 140 Asn Glu Val Glu Lys Cys Ile Cys Ile Leu Gln Ser Ser Cys Ile Asn 145 150 155 160 Met His Ser Ile Glu Gly Lys Asp Tyr Ile Ala Ser Leu Pro Phe Gln 165 170 175 Val Ala Asn Val Trp Pro Thr Lys Tyr Gly Leu Leu Phe Glu Arg Ser 180 185 190 Ala Ser Ser His Glu Val Pro Pro Gly Ser Pro Arg Glu Pro Leu Pro 195 200 205 Thr Met Phe Ser Met Leu His Pro Leu Asp Glu Ile Thr Pro Leu Val 210 215 220 Cys Lys Ser Gly Ser Leu Phe Gly Ser Ser Arg Val Gln Tyr Val Val 225 230 235 240 Asp His Ala Met Lys Ile Val Phe Leu Asn Thr Asp Pro Ser Ile Val 245 250 255 Met Thr Tyr Asp Ala Val Gln Asn Val His Ser Val Trp Thr Leu Arg 260 265 270 Arg Val Lys Ser Glu Glu Glu Asn Val Val Leu Lys Phe Ser Glu Gln 275 280 285 Gly Gly Thr Pro Gln Asn Val Ala Thr Ser Ser Ser Leu Thr Ala His 290 295 300 Leu Arg Ser Leu Ser Lys Gly Asp Ser Pro Val Thr Ser Pro Phe Gln 305 310 315 320 Asn Tyr Ser Ser Ile His Ser Gln Ser Arg Ser Thr Ser Ser Pro Ser 325 330 335 Leu His Ser Arg Ser Pro Ser Ile Ser Asn Met Ala Ala Leu Ser Arg 340 345 350 Ala His Ser Pro Ala Leu Gly Val His Ser Phe Ser Gly Val Gln Arg 355 360 365 Phe Asn Ile Ser Ser His Asn Gln Ser Pro Lys Arg His Ser Ile Ser 370 375 380 His Ser Pro Asn Ser Asn Ser Asn Gly Ser Phe Leu Ala Pro Glu Thr 385 390 395 400 Glu Pro Ile Val Pro Glu Leu Cys Ile Asp His Leu Trp Thr Glu Thr 405 410 415 Ile Thr Asn Ile Arg Glu Lys Asn Ser Gln Ala Ser Lys Val Phe Ile 420 425 430 Thr Ser Asp Leu Cys Gly Gln Lys Phe Leu Cys Phe Leu Val Glu Ser 435 440 445 Gln Leu Gln Leu Arg Cys Val Lys Phe Gln Glu Ser Asn Asp Lys Thr 450 455 460 Gln Leu Ile Phe Gly Ser Val Thr Asn Ile Pro Ala Lys Asp Ala Ala 465 470 475 480 Pro Val Glu Lys Ile Asp Thr Met Leu Val Leu Glu Gly Ser Gly Asn 485 490 495 Leu Val Leu Tyr Thr Gly Val Val Arg Val Gly Lys Val Phe Ile Pro 500 505 510 Gly Leu Pro Ala Pro Ser Leu Thr Met Ser Asn Thr Met Pro Arg Pro 515 520 525 Ser Thr Pro Leu Asp Gly Val Ser Thr Pro Lys Pro Leu Ser Lys Leu 530 535 540 Leu Gly Ser Leu Asp Glu Val Val Leu Leu Leu Ser Pro Val Pro Glu Leu 545 550 555 560 Arg Asp Ser Ser Lys Leu His Asp Ser Leu Tyr Asn Glu Asp Cys Thr 565 570 575 Phe Gln Gln Leu Gly Thr Tyr Ile His Ser Ile Arg Asp Pro Val His 580 585 590 Asn Arg Val Thr Leu Glu Leu Ser Asn Gly Ser Met Val Arg Ile Thr 595 600 605 Ile Pro Glu Ile Ala Thr Ser Glu Leu Val Gln Thr Cys Leu Gln Ala 610 615 620 Ile Lys Phe Ile Leu Pro Lys Glu Ile Ala Val Gln Met Leu Val Lys 625 630 635 640 Trp Tyr Asn Val His Ser Ala Pro Gly Gly Pro Ser Tyr His Ser Glu 645 650 655 Trp Asn Leu Phe Val Thr Cys Leu Met Asn Met Met Gly Tyr Asn Thr 660 665 670 Asp Arg Leu Ala Trp Thr Arg Asn Phe Asp Phe Glu Gly Ser Leu Ser 675 680 685 Pro Val Ile Ala Pro Lys Lys Ala Arg Pro Ser Glu Thr Gly Ser Asp 690 695 700 Asp Asp Trp Glu Tyr Leu Leu Asn Ser Asp Tyr His Gln Asn Val Glu 705 710 715 720 Ser His Leu Leu Asn Arg Ser Leu Cys Leu Ser Pro Ser Glu Ala Ser 725 730 735 Gln Met Lys Asp Glu Asp Phe Ser Gln Asn Leu Ser Leu Asp Ser Ser 740 745 750 Thr Leu Leu Phe Thr His Ile Pro Ala Ile Phe Phe Val Leu His Leu 755 760 765 Val Tyr Glu Glu Leu Lys Leu Asn Thr Leu Met Gly Glu Gly Ile Cys 770 775 780 Ser Leu Val Glu Leu Leu Val Gln Leu Ala Arg Asp Leu Lys Leu Gly 785 790 795 800 Pro Tyr Val Asp His Tyr Tyr Arg Asp Tyr Pro Thr Leu Val Arg Thr 805 810 815 Thr Gly Gln Val Cys Thr Ile Asp Pro Gly Gln Thr Gly Phe Met His 820 825 830 His Pro Ser Phe Phe Thr Ser Glu Pro Ser Ile Tyr Gln Trp Val 835 840 845 Ser Ser Cys Leu Lys Gly Glu Gly Met Pro Pro Tyr Pro Tyr Leu Pro 850 855 860 Gly Ile Cys Glu Arg Ser Arg Leu Val Val Leu Ser Ile Ala Leu Tyr 865 870 875 880 Ile Leu Gly Asp Glu Ser Leu Val Ser Asp Glu Ser Ser Gln Tyr Leu 885 890 895 Thr Arg Ile Thr Ile Ala Pro Gln Lys Leu Gln Val Glu Gln Glu Glu 900 905 910 Asn Arg Phe Ser Phe Arg His Ser Thr Ser Val Ser Leu Ala Glu 915 920 925 Arg Leu Val Val Trp Met Thr Asn Val Gly Phe Thr Leu Arg Asp Leu 930 935 940 Glu Thr Leu Pro Phe Gly Ile Ala Leu Pro Ile Arg Asp Ala Ile Tyr 945 950 955 960 His Cys Arg Glu Gln Pro Ala Ser Asp Trp Pro Glu Ala Val Cys Leu 965 970 975 Leu Ile Gly Arg Gln Asp Leu Ser Lys Gln Ala Cys Glu Gly Asn Leu 980 985 990 Pro Lys Gly Lys Ser Val Leu Ser Ser Asp Val Pro Ser Gly Thr Glu 995 1000 1005 Thr Glu Glu Glu Asp Asp Gly Met Asn Asp Met Asn His Glu Val Met 1010 1015 1020 Ser Leu Ile Trp Ser Glu Asp Leu Arg Val Gln Asp Val Arg Arg Leu 1025 1030 1035 1040 Leu Gln Ser Ala His Pro Val Arg Val Asn Val Val Gln Tyr Pro Glu 1045 1050 1055 Leu Ser Asp His Glu Phe Ile Glu Glu Lys Glu Asn Arg Leu Leu Gln 1060 1065 1070 Leu Cys Gln Arg Thr Met Ala Leu Pro Val Gly Arg Gly Met Phe Thr 1075 1080 1085 Leu Phe Ser Tyr His Pro Val Pro Thr Glu Pro Leu Pro Ile Pro Lys 1090 1095 1100 Leu Asn Leu Thr Gly Arg Ala Pro Pro Arg Asn Thr Thr Val Asp Leu 1105 1110 1115 1120 Asn Ser Gly Asn Ile Asp Val Pro Asn Met Thr Ser Trp Ala Ser 1125 1130 1135 Phe His Asn Gly Val Ala Ala Gly Leu Lys Ile Ala Pro Ala Ser Gln 1140 1145 1150 Ile Asp Ser Ala Trp Ile Val Tyr Asn Lys Pro Lys His Ala Glu Leu 1155 1160 1165 Ala Asn Glu Tyr Ala Gly Phe Leu Met Ala Leu Gly Leu Asn Gly His 1170 1175 1180 Leu Thr Lys Leu Ala Thr Leu Asn Ile His Asp Tyr Leu Thr Lys Gly 1185 1190 1195 1200 His Glu Met Thr Ser Ile Gly Leu Leu Leu Gly Val Ser Ala Ala Lys 1205 1210 1215 Leu Gly Thr Met Asp Met Ser Ile Thr Arg Leu Leu Ser Ile His Ile 1220 1225 1230 Pro Ala Leu Leu Pro Pro Thr Ser Thr Glu Leu Asp Val Pro His Asn 1235 1240 1245 Val Gln Val Ala Ala Val Val Gly Ile Gly Leu Val Tyr Gln Gly Thr 1250 1255 1260 Ala His Arg His Thr Ala Glu Val Leu Leu Ala Glu Ile Gly Arg Pro 1265 1270 1275 1280 Pro Gly Pro Glu Met Glu Tyr Cys Thr Asp Arg Glu Ser Tyr Ser Leu 1285 1290 1295 Ala Ala Gly Leu Ala Leu Gly Met Val Cys Leu Gly His Gly Ser Asn 1300 1305 1310 Leu Ile Gly Met Ser Asp Leu Asn Val Pro Glu Gln Leu Tyr Gln Tyr 1315 1320 1325 Met Val Gly Gly His Arg Arg Phe Gln Thr Gly Met His Arg Glu Lys 1330 1335 1340 His Lys Ser Pro Ser Tyr Gln Ile Lys Glu Gly Asp Thr Ile Asn Val 1345 1350 1355 1360 Asp Val Thr Cys Pro Gly Ala Thr Leu Ala Leu Ala Met Ile Tyr Leu 1365 1370 1375 Lys Thr Asn Asn Arg Ser Ile Ala Asp Trp Leu Arg Ala Pro Asp Thr 1380 1385 1390 Met Tyr Leu Leu Asp Phe Val Lys Pro Glu Phe Leu Leu Leu Leu Arg Thr 1395 1400 1405 Leu Ala Arg Cys Leu Ile Leu Trp Asp Asp Ile Leu Pro Asn Ser Lys 1410 1415 1420 Trp Val Asp Ser Asn Val Pro Gln Ile Ile Arg Glu Asn Ser Ile Ser 1425 1430 1435 1440 Leu Ser Glu Ile Glu Leu Pro Cys Ser Glu Asp Leu Asn Leu Glu Thr 1445 1450 1455 Leu Ser Gln Ala His Val Tyr Ile Ile Ala Gly Ala Cys Leu Ser Leu 1460 1465 1470 Gly Phe Arg Phe Ala Gly Ser Glu Asn Leu Ser Ala Phe Asn Cys Leu 1475 1480 1485 His Lys Phe Ala Lys Asp Phe Met Thr Tyr Leu Ser Ala Pro Asn Ala 1490 1495 1500 Ser Val Thr Gly Pro His Asn Leu Glu Thr Cys Leu Ser Val Val Leu 1505 1510 1515 1520 Leu Ser Leu Ala Met Val Met Ala Gly Ser Gly Asn Leu Lys Val Leu 1525 1530 1535 Gln Leu Cys Arg Phe Leu His Met Lys Thr Gly Gly Glu Met Asn Tyr 1540 1545 1550 Gly Phe His Leu Ala His His Met Ala Leu Gly Leu Leu Phe Leu Gly 1555 1560 1565 Gly Gly Arg Tyr Ser Leu Ser Thr Ser Asn Ser Ser Ile Ala Ala Leu 1570 1575 1580 Leu Cys Ala Leu Tyr Pro His Phe Pro Ala His Ser Thr Asp Asn Arg 1585 1590 1595 1600 Tyr His Leu Gln Ala Leu Arg His Leu Tyr Val Leu Ala Ala Glu Pro 1605 1610 1615 Arg Leu Leu Val Pro Val Asp Val Asp Thr Asn Thr Pro Cys Tyr Ala 1620 1625 1630 Leu Leu Glu Val Thr Tyr Lys Gly Thr Gln Trp Tyr Glu Gln Thr Lys 1635 1640 1645 Glu Glu Leu Met Ala Pro Thr Leu Leu Pro Glu Leu His Leu Leu Lys 1650 1655 1660 Gln Ile Lys Val Lys Gly Pro Arg Tyr Trp Glu Leu Leu Ile Asp Leu 1665 1670 1675 1680 Ser Lys Gly Thr Gln His Leu Lys Ser Ile Leu Ser Lys Asp Gly Val 1685 1690 1695 Leu Tyr Val Lys Leu Arg Ala Gly Gln Leu Ser Tyr Lys Glu Asp Pro 1700 1705 1710 Met Gly Trp Gln Ser Leu Leu Ala Gln Thr Val Ala Asn Arg Asn Ser 1715 1720 1725 Glu Ala Arg Ala Phe Lys Pro Glu Thr Ile Ser Ala Phe Thr Ser Asp 1730 1735 1740 Pro Ala Leu Leu Ser Phe Ala Glu Tyr Phe Cys Lys Pro Thr Val Asn 1745 1750 1755 1760 Met Gly Gln Lys Gln Glu Ile Leu Asp Leu Phe Ser Ser Val Leu Tyr 1765 1770 1775 Glu Cys Val Thr Gln Glu Thr Pro Glu Met Leu Pro Ala Tyr Ile Ala 1780 1785 1790 Met Asp Gln Ala Ile Arg Arg Leu Gly Arg Arg Glu Met Ser Glu Thr 1795 1800 1805 Ser Glu Leu Trp Gln Ile Lys Leu Val Leu Glu Phe Phe Ser Ser Arg 1810 1815 1820 Ser His Gln Glu Arg Leu Gln Asn His Pro Lys Arg Gly Leu Phe Met 1825 1830 1835 1840 Asn Ser Glu Phe Leu Pro Val Val Lys Cys Thr Ile Asp Asn Thr Leu 1845 1850 1855 Asp Gln Trp Leu Gln Val Gly Gly Asp Met Cys Val His Ala Tyr Leu 1860 1865 1870 Ser Gly Gln Pro Leu Glu Glu Ser Gln Leu Ser Met Leu Ala Cys Phe 1875 1880 1885 Leu Val Tyr His Ser Val Pro Ala Pro Gln His Leu Pro Pro Ile Gly 1890 1895 1900 Leu Glu Gly Ser Thr Ser Phe Ala Glu Leu Leu Phe Lys Phe Lys Gln 1905 1910 1915 1920 Leu Lys Met Pro Val Arg Ala Leu Leu Arg Leu Ala Pro Leu Leu Leu 1925 1930 1935 Gly Asn Pro Gln Pro Met Val Met 1940 <210> 3 <211> 717 <212> PRT <213> Homo sapiens <400> 3 Met Ala Thr Pro Ala Ala Val Asn Pro Pro Glu Met Ala Ser Asp Ile 1 5 10 15 Pro Gly Ser Val Thr Leu Pro Val Ala Pro Met Ala Ala Thr Gly Gln 20 25 30 Val Arg Met Ala Gly Ala Met Pro Ala Arg Gly Gly Lys Arg Arg Ser 35 40 45 Gly Met Asp Phe Asp Asp Glu Asp Gly Glu Gly Pro Ser Lys Phe Ser 50 55 60 Arg Glu Asn His Ser Glu Ile Glu Arg Arg Arg Arg Arg Asn Lys Met Thr 65 70 75 80 Gln Tyr Ile Thr Glu Leu Ser Asp Met Val Pro Thr Cys Ser Ala Leu 85 90 95 Ala Arg Lys Pro Asp Lys Leu Thr Ile Leu Arg Met Ala Val Ser His 100 105 110 Met Lys Ser Met Arg Gly Thr Gly Asn Lys Ser Thr Asp Gly Ala Tyr 115 120 125 Lys Pro Ser Phe Leu Thr Glu Gln Glu Leu Lys His Leu Ile Leu Glu 130 135 140 Ala Ala Asp Gly Phe Leu Phe Val Val Ala Ala Glu Thr Gly Arg Val 145 150 155 160 Ile Tyr Val Ser Asp Ser Val Thr Pro Val Leu Asn Gln Pro Gln Ser 165 170 175 Glu Trp Phe Gly Ser Thr Leu Tyr Glu Gln Val His Pro Asp Asp Val 180 185 190 Glu Lys Leu Arg Glu Gln Leu Cys Thr Ser Glu Asn Ser Met Thr Gly 195 200 205 Arg Ile Leu Asp Leu Lys Thr Gly Thr Val Lys Lys Glu Gly Gln Gln 210 215 220 Ser Ser Met Arg Met Cys Met Gly Ser Arg Arg Ser Phe Ile Cys Arg 225 230 235 240 Met Arg Cys Gly Asn Ala Pro Leu Asp His Leu Pro Leu Asn Arg Ile 245 250 255 Thr Thr Met Arg Lys Arg Phe Arg Asn Gly Leu Gly Pro Val Lys Glu 260 265 270 Gly Glu Ala Gln Tyr Ala Val Val His Cys Thr Gly Tyr Ile Lys Ala 275 280 285 Trp Pro Pro Ala Gly Met Thr Ile Pro Glu Glu Asp Ala Asp Val Gly 290 295 300 Gln Gly Ser Lys Tyr Cys Leu Val Ala Ile Gly Arg Leu Gln Val Thr 305 310 315 320 Ser Ser Pro Val Cys Met Asp Met Asn Gly Met Ser Val Pro Thr Glu 325 330 335 Phe Leu Ser Arg His Asn Ser Asp Gly Ile Ile Thr Phe Val Asp Pro 340 345 350 Arg Cys Ile Ser Val Ile Gly Tyr Gln Pro Gln Asp Leu Leu Gly Lys 355 360 365 Asp Ile Leu Glu Phe Cys His Pro Glu Asp Gln Ser His Leu Arg Glu 370 375 380 Ser Phe Gln Gln Val Val Lys Leu Lys Gly Gln Val Leu Ser Val Met 385 390 395 400 Tyr Arg Phe Arg Thr Lys Asn Arg Glu Trp Met Leu Ile Arg Thr Ser 405 410 415 Ser Phe Thr Phe Gln Asn Pro Tyr Ser Asp Glu Ile Glu Tyr Ile Ile 420 425 430 Cys Thr Asn Thr Asn Val Lys Gln Leu Gln Gln Gln Gln Ala Glu Leu 435 440 445 Glu Val His Gln Arg Asp Gly Leu Ser Ser Tyr Asp Leu Ser Gln Val 450 455 460 Pro Val Pro Asn Leu Pro Ala Gly Val His Glu Ala Gly Lys Ser Val 465 470 475 480 Glu Lys Ala Asp Ala Ile Phe Ser Gln Glu Arg Asp Pro Arg Phe Ala 485 490 495 Glu Met Phe Ala Gly Ile Ser Ala Ser Glu Lys Lys Met Met Ser Ser 500 505 510 Ala Ser Ala Ala Gly Thr Gln Gln Ile Tyr Ser Gln Gly Ser Pro Phe 515 520 525 Pro Ser Gly His Ser Gly Lys Ala Phe Ser Ser Ser Val Val His Val 530 535 540 Pro Gly Val Asn Asp Ile Gln Ser Ser Ser Ser Thr Gly Gln Asn Met 545 550 555 560 Ser Gln Ile Ser Arg Gln Leu Asn Gln Ser Gln Val Ala Trp Thr Gly 565 570 575 Ser Arg Pro Pro Phe Pro Gly Gln Gln Ile Pro Ser Gln Ser Ser Lys 580 585 590 Thr Gln Ser Ser Pro Phe Gly Ile Gly Thr Ser His Thr Tyr Pro Ala 595 600 605 Asp Pro Ser Ser Tyr Ser Pro Leu Ser Ser Pro Ala Thr Ser Ser Pro 610 615 620 Ser Gly Asn Ala Tyr Ser Ser Leu Ala Asn Arg Thr Pro Gly Phe Ala 625 630 635 640 Glu Ser Gly Gln Ser Ser Gly Gin Phe Gln Gly Arg Pro Ser Glu Val 645 650 655 Trp Ser Gln Trp Gln Ser Gln His His Gly Gln Gln Ser Gly Glu Gln 660 665 670 His Ser His Gln Gln Pro Gly Gln Thr Glu Val Phe Gln Asp Met Leu 675 680 685 Pro Met Pro Gly Asp Pro Thr Gln Gly Thr Gly Asn Tyr Asn Ile Glu 690 695 700 Asp Phe Ala Asp Leu Gly Met Phe Pro Pro Phe Ser Glu 705 710 715 <210> 4 <211> 505 <212> PRT <213> Homo sapiens <400> 4 Met Glu Gln Thr Glu Lys Ser Lys Val Tyr Ala Glu Asn Gly Leu Leu 1 5 10 15 Glu Lys Ile Lys Leu Cys Leu Ser Lys Lys Pro Leu Pro Ser Pro Thr 20 25 30 Glu Arg Lys Lys Phe Asp His Asp Phe Ala Ile Ser Thr Ser Phe His 35 40 45 Gly Ile His Asn Ile Val Gln Asn Arg Ser Lys Ile Arg Arg Val Leu 50 55 60 Trp Leu Val Val Val Leu Gly Ser Val Ser Leu Val Thr Trp Gln Ile 65 70 75 80 Tyr Ile Arg Leu Leu Asn Tyr Phe Thr Trp Pro Thr Thr Thr Ser Ile 85 90 95 Glu Val Gln Tyr Val Glu Lys Met Glu Phe Pro Ala Val Thr Phe Cys 100 105 110 Asn Leu Asn Arg Phe Gln Thr Asp Ala Val Ala Lys Phe Gly Val Ile 115 120 125 Phe Phe Leu Trp His Ile Val Ser Lys Val Leu His Leu Gln Glu Ile 130 135 140 Thr Ala Asn Ser Thr Gly Ser Arg Glu Ala Thr Asp Phe Ala Ala Ser 145 150 155 160 His Gln Asn Phe Ser Ile Val Glu Phe Ile Arg Asn Lys Gly Phe Tyr 165 170 175 Leu Asn Asn Ser Thr Leu Leu Asp Cys Glu Phe Phe Gly Lys Pro Cys 180 185 190 Ser Pro Lys Asp Phe Ala His Val Phe Thr Glu Tyr Gly Asn Cys Phe 195 200 205 Thr Phe Asn His Gly Glu Thr Leu Gln Ala Lys Arg Lys Val Ser Val 210 215 220 Ser Gly Arg Gly Leu Ser Leu Leu Phe Asn Val Asn Gln Glu Ala Phe 225 230 235 240 Thr Asp Asn Pro Ala Leu Gly Phe Val Asp Ala Gly Ile Ile Phe Val 245 250 255 Ile His Ser Pro Lys Lys Val Pro Gln Phe Asp Gly Leu Gly Leu Leu 260 265 270 Ser Pro Val Gly Met His Ala Arg Val Thr Ile Arg Gln Val Lys Thr 275 280 285 Val His Gln Glu Tyr Pro Trp Gly Glu Cys Asn Pro Asn Ile Lys Leu 290 295 300 Gln Asn Phe Ser Ser Tyr Ser Thr Ser Gly Cys Leu Lys Glu Cys Lys 305 310 315 320 Ala Gln His Ile Lys Lys Gln Cys Gly Cys Val Pro Phe Leu Leu Pro 325 330 335 Gly Tyr Gly Ile Glu Cys Asp Leu Gln Lys Tyr Phe Ser Cys Val Ser 340 345 350 Pro Val Leu Asp His Ile Glu Phe Lys Asp Leu Cys Thr Val Gly Thr 355 360 365 His Asn Ser Ser Cys Pro Val Ser Cys Glu Glu Ile Glu Tyr Pro Ala 370 375 380 Thr Ile Ser Tyr Ser Ser Phe Pro Ser Gln Lys Ala Leu Lys Tyr Leu 385 390 395 400 Ser Lys Lys Leu Asn Gln Ser Arg Lys Tyr Ile Arg Glu Asn Leu Val 405 410 415 Lys Ile Glu Ile Asn Tyr Ser Asp Leu Asn Tyr Lys Ile Thr Gln Gln 420 425 430 Gln Lys Ala Val Ser Val Ser Glu Leu Leu Ala Asp Leu Gly Gly Gln 435 440 445 Leu Gly Leu Phe Cys Gly Ala Ser Leu Ile Thr Ile Ile Glu Ile Ile 450 455 460 Glu Tyr Leu Phe Thr Asn Phe Tyr Trp Ile Cys Ile Phe Phe Leu Leu 465 470 475 480 Lys Ile Ser Glu Met Thr Gln Trp Thr Pro Pro Pro Gln Asn His Leu 485 490 495 Gly Asn Lys Asn Arg Ile Glu Glu Cys 500 505 <210> 5 <211> 4857 <212> PRT <213> Homo sapiens <400> 5 Met Val Thr Gly Gly Gly Ala Ala Pro Pro Gly Thr Val Thr Glu Pro 1 5 10 15 Leu Pro Ser Val Ile Val Leu Ser Ala Gly Arg Lys Met Ala Ala Ala 20 25 30 Ala Ala Ala Ala Ser Gly Pro Gly Cys Ser Ser Ala Ala Gly Ala Gly 35 40 45 Ala Ala Gly Val Ser Glu Trp Leu Val Leu Arg Asp Gly Cys Met His 50 55 60 Cys Asp Ala Asp Gly Leu His Ser Leu Ser Tyr His Pro Ala Leu Asn 65 70 75 80 Ala Ile Leu Ala Val Thr Ser Arg Gly Thr Ile Lys Val Ile Asp Gly 85 90 95 Thr Ser Gly Ala Thr Leu Gln Ala Ser Ala Leu Ser Ala Lys Pro Gly 100 105 110 Gly Gln Val Lys Cys Gln Tyr Ile Ser Ala Val Asp Lys Val Ile Phe 115 120 125 Val Asp Asp Tyr Ala Val Gly Cys Arg Lys Asp Leu Asn Gly Ile Leu 130 135 140 Leu Leu Asp Thr Ala Leu Gln Thr Pro Val Ser Lys Gln Asp Asp Val 145 150 155 160 Val Gln Leu Glu Leu Pro Val Thr Glu Ala Gln Gln Leu Leu Ser Ala 165 170 175 Cys Leu Glu Lys Val Asp Ile Ser Ser Thr Glu Gly Tyr Asp Leu Phe 180 185 190 Ile Thr Gln Leu Lys Asp Gly Leu Lys Asn Thr Ser His Glu Thr Ala 195 200 205 Ala Asn His Lys Val Ala Lys Trp Ala Thr Val Thr Phe His Leu Pro 210 215 220 His His Val Leu Lys Ser Ile Ala Ser Ala Ile Val Asn Glu Leu Lys 225 230 235 240 Lys Ile Asn Gln Asn Val Ala Ala Leu Pro Val Ala Ser Ser Val Met 245 250 255 Asp Arg Leu Ser Tyr Leu Leu Pro Ser Ala Arg Pro Glu Leu Gly Val 260 265 270 Gly Pro Gly Arg Ser Val Asp Arg Ser Leu Met Tyr Ser Glu Ala Asn 275 280 285 Arg Arg Glu Thr Phe Thr Ser Trp Pro His Val Gly Tyr Arg Trp Ala 290 295 300 Gln Pro Asp Pro Met Ala Gln Ala Gly Phe Tyr His Gln Pro Ala Ser 305 310 315 320 Ser Gly Asp Asp Arg Ala Met Cys Phe Thr Cys Ser Val Cys Leu Val 325 330 335 Cys Trp Glu Pro Thr Asp Glu Pro Trp Ser Glu His Glu Arg His Ser 340 345 350 Pro Asn Cys Pro Phe Val Lys Gly Glu His Thr Gln Asn Val Pro Leu 355 360 365 Ser Val Thr Leu Ala Thr Ser Pro Ala Gln Phe Pro Cys Thr Asp Gly 370 375 380 Thr Asp Arg Ile Ser Cys Phe Gly Ser Gly Ser Cys Pro His Phe Leu 385 390 395 400 Ala Ala Ala Thr Lys Arg Gly Lys Ile Cys Ile Trp Asp Val Ser Lys 405 410 415 Leu Met Lys Val His Leu Lys Phe Glu Ile Asn Ala Tyr Asp Pro Ala 420 425 430 Ile Val Gln Gln Leu Ile Leu Ser Gly Asp Pro Ser Ser Gly Val Asp 435 440 445 Ser Arg Arg Pro Thr Leu Ala Trp Leu Glu Asp Ser Ser Ser Cys Ser 450 455 460 Asp Ile Pro Lys Leu Glu Gly Asp Ser Asp Asp Leu Leu Glu Asp Ser 465 470 475 480 Asp Ser Glu Glu His Ser Arg Ser Asp Ser Val Thr Gly His Thr Ser 485 490 495 Gln Lys Glu Ala Met Glu Val Ser Leu Asp Ile Thr Ala Leu Ser Ile 500 505 510 Leu Gln Gln Pro Glu Lys Leu Gln Trp Glu Ile Val Ala Asn Val Leu 515 520 525 Glu Asp Thr Val Lys Asp Leu Glu Glu Leu Gly Ala Asn Pro Cys Leu 530 535 540 Thr Asn Ser Lys Ser Glu Lys Thr Lys Glu Lys His Gln Glu Gln His 545 550 555 560 Asn Ile Pro Phe Pro Cys Leu Leu Ala Gly Gly Leu Leu Thr Tyr Lys 565 570 575 Ser Pro Ala Thr Ser Pro Ile Ser Ser Asn Ser His Arg Ser Leu Asp 580 585 590 Gly Leu Ser Arg Thr Gln Gly Glu Ser Ile Ser Glu Gln Gly Ser Thr 595 600 605 Asp Asn Glu Ser Cys Thr Asn Ser Glu Leu Asn Ser Pro Leu Val Arg 610 615 620 Arg Thr Leu Pro Val Leu Leu Leu Tyr Ser Ile Lys Glu Ser Asp Glu 625 630 635 640 Lys Ala Gly Lys Ile Phe Ser Gln Met Asn Asn Ile Met Ser Lys Ser 645 650 655 Leu His Asp Asp Gly Phe Thr Val Pro Gln Ile Ile Glu Met Glu Leu 660 665 670 Asp Ser Gln Glu Gln Leu Leu Leu Gln Asp Pro Pro Val Thr Tyr Ile 675 680 685 Gln Gln Phe Ala Asp Ala Ala Ala Asn Leu Thr Ser Pro Asp Ser Glu 690 695 700 Lys Trp Asn Ser Val Phe Pro Lys Pro Gly Thr Leu Val Gln Cys Leu 705 710 715 720 Arg Leu Pro Lys Phe Ala Glu Glu Glu Asn Leu Cys Ile Asp Ser Ile 725 730 735 Thr Pro Cys Ala Asp Gly Ile His Leu Leu Val Gly Leu Arg Thr Cys 740 745 750 Pro Val Glu Ser Leu Ser Ala Ile Asn Gln Val Glu Ala Leu Asn Asn 755 760 765 Leu Asn Lys Leu Asn Ser Ala Leu Cys Asn Arg Arg Lys Gly Glu Leu 770 775 780 Glu Ser Asn Leu Ala Val Val Asn Gly Ala Asn Ile Ser Val Ile Gln 785 790 795 800 His Glu Ser Pro Ala Asp Val Gln Thr Pro Leu Ile Ile Gln Pro Glu 805 810 815 Gln Arg Asn Val Ser Gly Gly Tyr Leu Val Leu Tyr Lys Met Asn Tyr 820 825 830 Ala Thr Arg Ile Val Thr Leu Glu Glu Glu Pro Ile Lys Ile Gln His 835 840 845 Ile Lys Asp Pro Gln Asp Thr Ile Thr Ser Leu Ile Leu Leu Pro Pro 850 855 860 Asp Ile Leu Asp Asn Arg Glu Asp Asp Cys Glu Glu Pro Ile Glu Asp 865 870 875 880 Met Gln Leu Thr Ser Lys Asn Gly Phe Glu Arg Glu Lys Thr Ser Asp 885 890 895 Ile Ser Thr Leu Gly His Leu Val Ile Thr Thr Gln Gly Gly Tyr Val 900 905 910 Lys Ile Leu Asp Leu Ser Asn Phe Glu Ile Leu Ala Lys Val Glu Pro 915 920 925 Pro Lys Lys Glu Gly Thr Glu Glu Gln Asp Thr Phe Val Ser Val Ile 930 935 940 Tyr Cys Ser Gly Thr Asp Arg Leu Cys Ala Cys Thr Lys Gly Gly Glu 945 950 955 960 Leu His Phe Leu Gln Ile Gly Gly Thr Cys Asp Asp Ile Asp Glu Ala 965 970 975 Asp Ile Leu Val Asp Gly Ser Leu Ser Lys Gly Ile Glu Pro Ser Ser 980 985 990 Glu Gly Ser Lys Pro Leu Ser Asn Pro Ser Ser Pro Gly Ile Ser Gly 995 1000 1005 Val Asp Leu Leu Val Asp Gln Pro Phe Thr Leu Glu Ile Leu Thr Ser 1010 1015 1020 Leu Val Glu Leu Thr Arg Phe Glu Thr Leu Thr Pro Arg Phe Ser Ala 1025 1030 1035 1040 Thr Val Pro Pro Cys Trp Val Glu Val Gln Gln Glu Gln Gln Gln Arg 1045 1050 1055 Arg His Pro Gln His Leu His Gln Gln His His Gly Asp Ala Ala Gln 1060 1065 1070 His Thr Arg Thr Trp Lys Leu Gln Thr Asp Ser Asn Ser Trp Asp Glu 1075 1080 1085 His Val Phe Glu Leu Val Leu Pro Lys Ala Cys Met Val Gly His Val 1090 1095 1100 Asp Phe Lys Phe Val Leu Asn Ser Asn Ile Thr Asn Ile Pro Gln Ile 1105 1110 1115 1120 Gln Val Thr Leu Leu Lys Asn Lys Ala Pro Gly Leu Gly Lys Val Asn 1125 1130 1135 Ala Leu Asn Ile Glu Val Glu Gln Asn Gly Lys Pro Ser Leu Val Asp 1140 1145 1150 Leu Asn Glu Glu Met Gln His Met Asp Val Glu Glu Ser Gln Cys Leu 1155 1160 1165 Arg Leu Cys Pro Phe Leu Glu Asp His Lys Glu Asp Ile Leu Cys Gly 1170 1175 1180 Pro Val Trp Leu Ala Ser Gly Leu Asp Leu Ser Gly His Ala Gly Met 1185 1190 1195 1200 Leu Thr Leu Thr Ser Pro Lys Leu Val Lys Gly Met Ala Gly Gly Lys 1205 1210 1215 Tyr Arg Ser Phe Leu Ile His Val Lys Ala Val Asn Glu Arg Gly Thr 1220 1225 1230 Glu Glu Ile Cys Asn Gly Gly Met Arg Pro Val Val Arg Leu Pro Ser 1235 1240 1245 Leu Lys His Gln Ser Asn Lys Gly Tyr Ser Leu Ala Ser Leu Leu Ala 1250 1255 1260 Lys Val Ala Ala Gly Lys Glu Lys Ser Ser Asn Val Lys Asn Glu Asn 1265 1270 1275 1280 Thr Ser Gly Thr Arg Lys Ser Glu Asn Leu Arg Gly Cys Asp Leu Leu 1285 1290 1295 Gln Glu Val Ser Val Thr Ile Arg Arg Phe Lys Lys Thr Ser Ile Ser 1300 1305 1310 Lys Glu Arg Val Gln Arg Cys Ala Met Leu Gln Phe Ser Glu Phe His 1315 1320 1325 Glu Lys Leu Leu Asn Thr Leu Cys Arg Lys Thr Asp Asp Gly Gln Ile 1330 1335 1340 Thr Glu His Ala Gln Ser Leu Val Leu Asp Thr Leu Cys Trp Leu Ala 1345 1350 1355 1360 Gly Val His Ser Asn Gly Pro Gly Ser Ser Lys Glu Gly Asn Glu Asn 1365 1370 1375 Leu Leu Ser Lys Thr Arg Lys Phe Leu Ser Asp Ile Val Arg Val Cys 1380 1385 1390 Phe Phe Glu Ala Gly Arg Ser Ile Ala His Lys Cys Ala Arg Phe Leu 1395 1400 1405 Ala Leu Cys Ile Ser Asn Gly Lys Cys Asp Pro Cys Gln Pro Ala Phe 1410 1415 1420 Gly Pro Val Leu Leu Lys Ala Leu Leu Asp Asn Met Ser Phe Leu Pro 1425 1430 1435 1440 Ala Ala Thr Thr Gly Gly Ser Val Tyr Trp Tyr Phe Val Leu Leu Asn 1445 1450 1455 Tyr Val Lys Asp Glu Asp Leu Ala Gly Cys Ser Thr Ala Cys Ala Ser 1460 1465 1470 Leu Leu Thr Ala Val Ser Arg Gln Leu Gln Asp Arg Leu Thr Pro Met 1475 1480 1485 Glu Ala Leu Leu Gln Thr Arg Tyr Gly Leu Tyr Ser Ser Pro Phe Asp 1490 1495 1500 Pro Val Leu Phe Asp Leu Glu Met Ser Gly Ser Ser Cys Lys Asn Val 1505 1510 1515 1520 Tyr Asn Ser Ser Ile Gly Val Gln Ser Asp Glu Ile Asp Leu Ser Asp 1525 1530 1535 Val Leu Ser Gly Asn Gly Lys Val Ser Ser Cys Thr Ala Ala Glu Gly 1540 1545 1550 Ser Phe Thr Ser Leu Thr Gly Leu Leu Glu Val Glu Pro Leu His Phe 1555 1560 1565 Thr Cys Val Ser Thr Ser Asp Gly Thr Arg Ile Glu Arg Asp Asp Ala 1570 1575 1580 Met Ser Ser Phe Gly Val Thr Pro Ala Val Gly Gly Leu Ser Ser Gly 1585 1590 1595 1600 Thr Val Gly Glu Ala Ser Thr Ala Leu Ser Ser Ala Ala Gln Val Ala 1605 1610 1615 Leu Gln Ser Leu Ser His Ala Met Ala Ser Ala Glu Gln Gln Leu Gln 1620 1625 1630 Val Leu Gln Glu Lys Gln Gln Gln Leu Leu Lys Leu Gln Gln Gln Lys 1635 1640 1645 Ala Lys Leu Glu Ala Lys Leu His Gln Thr Thr Ala Ala Ala Ala Ala 1650 1655 1660 Ala Ala Ser Ala Val Gly Pro Val His Asn Ser Val Pro Ser Asn Pro 1665 1670 1675 1680 Val Ala Ala Pro Gly Phe Phe Ile His Pro Ser Asp Val Ile Pro Pro 1685 1690 1695 Thr Pro Lys Thr Thr Pro Leu Phe Met Thr Pro Pro Leu Thr Pro Pro 1700 1705 1710 Asn Glu Ala Val Ser Val Val Ile Asn Ala Glu Leu Ala Gln Leu Phe 1715 1720 1725 Pro Gly Ser Val Ile Asp Pro Pro Ala Val Asn Leu Ala Ala His Asn 1730 1735 1740 Lys Asn Ser Asn Lys Ser Arg Met Asn Pro Leu Gly Ser Gly Leu Ala 1745 1750 1755 1760 Leu Ala Ile Ser His Ala Ser His Phe Leu Gln Pro Pro His Gln 1765 1770 1775 Ser Ile Ile Ile Glu Arg Met His Ser Gly Ala Arg Arg Phe Val Thr 1780 1785 1790 Leu Asp Phe Gly Arg Pro Ile Leu Leu Thr Asp Val Leu Ile Pro Thr 1795 1800 1805 Cys Gly Asp Leu Ala Ser Leu Ser Ile Asp Ile Trp Thr Leu Gly Glu 1810 1815 1820 Glu Val Asp Gly Arg Arg Leu Val Val Ala Thr Asp Ile Ser Thr His 1825 1830 1835 1840 Ser Leu Ile Leu His Asp Leu Ile Pro Pro Val Cys Arg Phe Met 1845 1850 1855 Lys Ile Thr Val Ile Gly Arg Tyr Gly Ser Thr Asn Ala Arg Ala Lys 1860 1865 1870 Ile Pro Leu Gly Phe Tyr Tyr Gly His Thr Tyr Ile Leu Pro Trp Glu 1875 1880 1885 Ser Glu Leu Lys Leu Met His Asp Pro Leu Lys Gly Glu Gly Glu Ser 1890 1895 1900 Ala Asn Gln Pro Glu Ile Asp Gln His Leu Ala Met Met Val Ala Leu 1905 1910 1915 1920 Gln Glu Asp Ile Gln Cys Arg Tyr Asn Leu Ala Cys His Arg Leu Glu 1925 1930 1935 Thr Leu Leu Gln Ser Ile Asp Leu Pro Pro Leu Asn Ser Ala Asn Asn 1940 1945 1950 Ala Gln Tyr Phe Leu Arg Lys Pro Asp Lys Ala Val Glu Glu Asp Ser 1955 1960 1965 Arg Val Phe Ser Ala Tyr Gln Asp Cys Ile Gln Leu Gln Leu Gln Leu 1970 1975 1980 Asn Leu Ala His Asn Ala Val Gln Arg Leu Lys Val Ala Leu Gly Ala 1985 1990 1995 2000 Ser Arg Lys Met Leu Ser Glu Thr Ser Asn Pro Glu Asp Leu Ile Gln 2005 2010 2015 Thr Ser Ser Thr Glu Gln Leu Arg Thr Ile Ile Arg Tyr Leu Leu Asp 2020 2025 2030 Thr Leu Leu Ser Leu Leu His Ala Ser Asn Gly His Ser Val Pro Ala 2035 2040 2045 Val Leu Gln Ser Thr Phe His Ala Gln Ala Cys Glu Glu Leu Phe Lys 2050 2055 2060 His Leu Cys Ile Ser Gly Thr Pro Lys Ile Arg Leu His Thr Gly Leu 2065 2070 2075 2080 Leu Leu Val Gln Leu Cys Gly Gly Glu Arg Trp Trp Gly Gln Phe Leu 2085 2090 2095 Ser Asn Val Leu Gln Glu Leu Tyr Asn Ser Glu Gln Leu Leu Ile Phe 2100 2105 2110 Pro Gln Asp Arg Val Phe Met Leu Leu Ser Cys Ile Gly Gln Arg Ser 2115 2120 2125 Leu Ser Asn Ser Gly Val Leu Glu Ser Leu Leu Asn Leu Leu Asp Asn 2130 2135 2140 Leu Leu Ser Pro Leu Gln Pro Gln Leu Pro Met His Arg Arg Thr Glu 2145 2150 2155 2160 Gly Val Leu Asp Ile Pro Met Ile Ser Trp Val Val Met Leu Val Ser 2165 2170 2175 Arg Leu Leu Asp Tyr Val Ala Thr Val Glu Asp Glu Ala Ala Ala Ala 2180 2185 2190 Lys Lys Pro Leu Asn Gly Asn Gln Trp Ser Phe Ile Asn Asn Asn Leu 2195 2200 2205 His Thr Gln Ser Leu Asn Arg Ser Ser Lys Gly Ser Ser Ser Leu Asp 2210 2215 2220 Arg Leu Tyr Ser Arg Lys Ile Arg Lys Gln Leu Val His His Lys Gln 2225 2230 2235 2240 Gln Leu Asn Leu Leu Lys Ala Lys Gln Lys Ala Leu Val Glu Gln Met 2245 2250 2255 Glu Lys Glu Lys Ile Gln Ser Asn Lys Gly Ser Ser Tyr Lys Leu Leu 2260 2265 2270 Val Glu Gln Ala Lys Leu Lys Gln Ala Thr Ser Lys His Phe Lys Asp 2275 2280 2285 Leu Ile Arg Leu Arg Arg Thr Ala Glu Trp Ser Arg Ser Asn Leu Asp 2290 2295 2300 Thr Glu Val Thr Thr Ala Lys Glu Ser Pro Glu Ile Glu Pro Leu Pro 2305 2310 2315 2320 Phe Thr Leu Ala His Glu Arg Cys Ile Ser Val Val Gln Lys Leu Val 2325 2330 2335 Leu Phe Leu Leu Ser Met Asp Phe Thr Cys His Ala Asp Leu Leu Leu 2340 2345 2350 Phe Val Cys Lys Val Leu Ala Arg Ile Ala Asn Ala Thr Arg Pro Thr 2355 2360 2365 Ile His Leu Cys Glu Ile Val Asn Glu Pro Gln Leu Glu Arg Leu Leu 2370 2375 2380 Leu Leu Leu Val Gly Thr Asp Phe Asn Arg Gly Asp Ile Ser Trp Gly 2385 2390 2395 2400 Gly Ala Trp Ala Gln Tyr Ser Leu Thr Cys Met Leu Gln Asp Ile Leu 2405 2410 2415 Ala Gly Glu Leu Leu Ala Pro Val Ala Ala Glu Ala Met Glu Glu Gly 2420 2425 2430 Thr Val Gly Asp Asp Val Gly Ala Thr Ala Gly Asp Ser Asp Asp Ser 2435 2440 2445 Leu Gln Gln Ser Ser Val Gln Leu Leu Glu Thr Ile Asp Glu Pro Leu 2450 2455 2460 Thr His Asp Ile Thr Gly Ala Pro Leu Ser Ser Leu Glu Lys Asp 2465 2470 2475 2480 Lys Glu Ile Asp Leu Glu Leu Leu Gln Asp Leu Met Glu Val Asp Ile 2485 2490 2495 Asp Pro Leu Asp Ile Asp Leu Glu Lys Asp Pro Leu Ala Ala Lys Val 2500 2505 2510 Phe Lys Pro Ile Ser Ser Thr Trp Tyr Asp Tyr Trp Gly Ala Asp Tyr 2515 2520 2525 Gly Thr Tyr Asn Tyr Asn Pro Tyr Ile Gly Gly Leu Gly Ile Pro Val 2530 2535 2540 Ala Lys Pro Pro Ala Asn Thr Glu Lys Asn Gly Ser Gln Thr Val Ser 2545 2550 2555 2560 Val Ser Val Ser Gln Ala Leu Asp Ala Arg Leu Glu Val Gly Leu Glu 2565 2570 2575 Gln Gln Ala Glu Leu Met Leu Lys Met Met Ser Thr Leu Glu Ala Asp 2580 2585 2590 Ser Ile Leu Gln Ala Leu Thr Asn Thr Ser Pro Thr Leu Ser Gln Ser 2595 2600 2605 Pro Thr Gly Thr Asp Asp Ser Leu Leu Gly Gly Leu Gln Ala Ala Asn 2610 2615 2620 Gln Thr Ser Gln Leu Ile Ile Gln Leu Ser Ser Val Pro Met Leu Asn 2625 2630 2635 2640 Val Cys Phe Asn Lys Leu Phe Ser Met Leu Gln Val His His Val Gln 2645 2650 2655 Leu Glu Ser Leu Leu Gln Leu Trp Leu Thr Leu Ser Leu Asn Ser Ser 2660 2665 2670 Ser Thr Gly Asn Lys Glu Asn Gly Ala Asp Ile Phe Leu Tyr Asn Ala 2675 2680 2685 Asn Arg Ile Pro Val Ile Ser Leu Asn Gln Ala Ser Ile Thr Ser Phe 2690 2695 2700 Leu Thr Val Leu Ala Trp Tyr Pro Asn Thr Leu Leu Arg Thr Trp Cys 2705 2710 2715 2720 Leu Val Leu His Ser Leu Thr Leu Met Thr Asn Met Gln Leu Asn Ser 2725 2730 2735 Gly Ser Ser Ser Ala Ile Gly Thr Gln Glu Ser Thr Ala His Leu Leu 2740 2745 2750 Val Ser Asp Pro Asn Leu Ile His Val Leu Val Lys Phe Leu Ser Gly 2755 2760 2765 Thr Ser Pro His Gly Thr Asn Gln His Ser Pro Gln Val Gly Pro Thr 2770 2775 2780 Ala Thr Gln Ala Met Gln Glu Phe Leu Thr Arg Leu Gln Val His Leu 2785 2790 2795 2800 Ser Ser Thr Cys Pro Gln Ile Phe Ser Glu Phe Leu Leu Lys Leu Ile 2805 2810 2815 His Ile Leu Ser Thr Glu Arg Gly Ala Phe Gln Thr Gly Gln Gly Pro 2820 2825 2830 Leu Asp Ala Gln Val Lys Leu Leu Glu Phe Thr Leu Glu Gln Asn Phe 2835 2840 2845 Glu Val Val Ser Val Ser Thr Ile Ser Ala Val Ile Glu Ser Val Thr 2850 2855 2860 Phe Leu Val His His Tyr Ile Thr Cys Ser Asp Lys Val Met Ser Arg 2865 2870 2875 2880 Ser Gly Ser Asp Ser Ser Val Gly Ala Arg Ala Cys Phe Gly Gly Leu 2885 2890 2895 Phe Ala Asn Leu Ile Arg Pro Gly Asp Ala Lys Ala Val Cys Gly Glu 2900 2905 2910 Met Thr Arg Asp Gln Leu Met Phe Asp Leu Leu Lys Leu Val Asn Ile 2915 2920 2925 Leu Val Gln Leu Pro Leu Ser Gly Asn Arg Glu Tyr Ser Ala Arg Val 2930 2935 2940 Ser Val Thr Thr Asn Thr Thr Asp Ser Val Ser Asp Glu Glu Lys Val 2945 2950 2955 2960 Ser Gly Gly Lys Asp Gly Asn Gly Ser Ser Thr Ser Val Gln Gly Ser 2965 2970 2975 Pro Ala Tyr Val Ala Asp Leu Val Leu Ala Asn Gln Gln Ile Met Ser 2980 2985 2990 Gln Ile Leu Ser Ala Leu Gly Leu Cys Asn Ser Ser Ala Met Ala Met 2995 3000 3005 Ile Ile Gly Ala Ser Gly Leu His Leu Thr Lys His Glu Asn Phe His 3010 3015 3020 Gly Gly Leu Asp Ala Ile Ser Val Gly Asp Gly Leu Phe Thr Ile Leu 3025 3030 3035 3040 Thr Thr Leu Ser Lys Lys Ala Ser Thr Val His Met Met Leu Gln Pro 3045 3050 3055 Ile Leu Thr Tyr Met Ala Cys Gly Tyr Met Gly Arg Gln Gly Ser Leu 3060 3065 3070 Ala Thr Cys Gln Leu Ser Glu Pro Leu Leu Trp Phe Ile Leu Arg Val 3075 3080 3085 Leu Asp Thr Ser Asp Ala Leu Lys Ala Phe His Asp Met Gly Gly Val 3090 3095 3100 Gln Leu Ile Cys Asn Asn Met Val Thr Ser Thr Arg Ala Ile Val Asn 3105 3110 3115 3120 Thr Ala Arg Ser Met Val Ser Thr Ile Met Lys Phe Leu Asp Ser Gly 3125 3130 3135 Pro Asn Lys Ala Val Asp Ser Thr Leu Lys Thr Arg Ile Leu Ala Ser 3140 3145 3150 Glu Pro Asp Asn Ala Glu Gly Ile His Asn Phe Ala Pro Leu Gly Thr 3155 3160 3165 Ile Thr Ser Ser Ser Pro Thr Ala Gln Pro Ala Glu Val Leu Leu Gln 3170 3175 3180 Ala Thr Pro Pro His Arg Arg Ala Arg Ser Ala Ala Trp Ser Tyr Ile 3185 3190 3195 3200 Phe Leu Pro Glu Glu Ala Trp Cys Asp Leu Thr Ile His Leu Pro Ala 3205 3210 3215 Ala Val Leu Leu Lys Glu Ile His Ile Gln Pro His Leu Ala Ser Leu 3220 3225 3230 Ala Thr Cys Pro Ser Ser Val Ser Val Glu Val Ser Ala Asp Gly Val 3235 3240 3245 Asn Met Leu Pro Leu Ser Thr Pro Val Val Thr Ser Gly Leu Thr Tyr 3250 3255 3260 Ile Lys Ile Gln Leu Val Lys Ala Glu Val Ala Ser Ala Val Cys Leu 3265 3270 3275 3280 Arg Leu His Arg Pro Arg Asp Ala Ser Thr Leu Gly Leu Ser Gln Ile 3285 3290 3295 Lys Leu Leu Gly Leu Thr Ala Phe Gly Thr Thr Ser Ser Ala Thr Val 3300 3305 3310 Asn Asn Pro Phe Leu Pro Ser Glu Asp Gln Val Ser Lys Thr Ser Ile 3315 3320 3325 Gly Trp Leu Arg Leu Leu His His Cys Leu Thr His Ile Ser Asp Leu 3330 3335 3340 Glu Gly Met Met Ala Ser Ala Ala Ala Pro Thr Ala Asn Leu Leu Gln 3345 3350 3355 3360 Thr Cys Ala Ala Leu Leu Met Ser Pro Tyr Cys Gly Met His Ser Pro 3365 3370 3375 Asn Ile Glu Val Val Leu Val Lys Ile Gly Leu Gln Ser Thr Arg Ile 3380 3385 3390 Gly Leu Lys Leu Ile Asp Ile Leu Leu Arg Asn Cys Ala Ala Ser Gly 3395 3400 3405 Ser Asp Pro Thr Asp Leu Asn Ser Pro Leu Leu Phe Gly Arg Leu Asn 3410 3415 3420 Gly Leu Ser Ser Asp Ser Thr Ile Asp Ile Leu Tyr Gln Leu Gly Thr 3425 3430 3435 3440 Thr Gln Asp Pro Gly Thr Lys Asp Arg Ile Gln Ala Leu Leu Lys Trp 3445 3450 3455 Val Ser Asp Ser Ala Arg Val Ala Ala Met Lys Arg Ser Gly Arg Met 3460 3465 3470 Asn Tyr Met Cys Pro Asn Ser Ser Thr Val Glu Tyr Gly Leu Leu Met 3475 3480 3485 Pro Ser Pro Ser His Leu His Cys Val Ala Ala Ile Leu Trp His Ser 3490 3495 3500 Tyr Glu Leu Leu Val Glu Tyr Asp Leu Pro Ala Leu Leu Asp Gln Glu 3505 3510 3515 3520 Leu Phe Glu Leu Leu Phe Asn Trp Ser Met Ser Leu Pro Cys Asn Met 3525 3530 3535 Val Leu Lys Lys Ala Val Asp Ser Leu Leu Cys Ser Met Cys His Val 3540 3545 3550 His Pro Asn Tyr Phe Ser Leu Leu Met Gly Trp Met Gly Ile Thr Pro 3555 3560 3565 Pro Pro Val Gln Cys His His Arg Leu Ser Met Thr Asp Asp Ser Lys 3570 3575 3580 Lys Gln Asp Leu Ser Ser Ser Leu Thr Asp Asp Ser Lys Asn Ala Gln 3585 3590 3595 3600 Ala Pro Leu Ala Leu Thr Glu Ser His Leu Ala Thr Leu Ala Ser Ser 3605 3610 3615 Ser Gln Ser Pro Glu Ala Ile Lys Gln Leu Leu Asp Ser Gly Leu Pro 3620 3625 3630 Ser Leu Leu Val Arg Ser Leu Ala Ser Phe Cys Phe Ser His Ile Ser 3635 3640 3645 Ser Ser Glu Ser Ile Ala Gln Ser Ile Asp Ile Ser Gln Asp Lys Leu 3650 3655 3660 Arg Arg His His Val Pro Gln Gln Cys Asn Lys Met Pro Ile Thr Ala 3665 3670 3675 3680 Asp Leu Val Ala Pro Ile Leu Arg Phe Leu Thr Glu Val Gly Asn Ser 3685 3690 3695 His Ile Met Lys Asp Trp Leu Gly Gly Ser Glu Val Asn Pro Leu Trp 3700 3705 3710 Thr Ala Leu Leu Phe Leu Leu Cys His Ser Gly Ser Thr Ser Gly Ser 3715 3720 3725 His Asn Leu Gly Ala Gln Gln Thr Ser Ala Arg Ser Ala Ser Leu Ser 3730 3735 3740 Ser Ala Ala Thr Thr Gly Leu Thr Thr Gln Gln Arg Thr Ala Ile Glu 3745 3750 3755 3760 Asn Ala Thr Val Ala Phe Phe Leu Gln Cys Ile Ser Cys His Pro Asn 3765 3770 3775 Asn Gln Lys Leu Met Ala Gln Val Leu Cys Glu Leu Phe Gln Thr Ser 3780 3785 3790 Pro Gln Arg Gly Asn Leu Pro Thr Ser Gly Asn Ile Ser Gly Phe Ile 3795 3800 3805 Arg Arg Leu Phe Leu Gln Leu Met Leu Glu Asp Glu Lys Val Thr Met 3810 3815 3820 Phe Leu Gln Ser Pro Cys Pro Leu Tyr Lys Gly Arg Ile Asn Ala Thr 3825 3830 3835 3840 Ser His Val Ile Gln His Pro Met Tyr Gly Ala Gly His Lys Phe Arg 3845 3850 3855 Thr Leu His Leu Pro Val Ser Thr Thr Leu Ser Asp Val Leu Asp Arg 3860 3865 3870 Val Ser Asp Thr Pro Ser Ile Thr Ala Lys Leu Ile Ser Glu Gln Lys 3875 3880 3885 Asp Asp Lys Glu Lys Lys Asn His Glu Glu Lys Glu Lys Val Lys Ala 3890 3895 3900 Glu Asn Gly Phe Gln Asp Asn Tyr Ser Val Val Val Ala Ser Gly Leu 3905 3910 3915 3920 Lys Ser Gln Ser Lys Arg Ala Val Ser Ala Thr Pro Pro Arg Pro Pro 3925 3930 3935 Ser Arg Arg Gly Arg Thr Ile Pro Asp Lys Ile Gly Ser Thr Ser Gly 3940 3945 3950 Ala Glu Ala Ala Asn Lys Ile Ile Thr Val Pro Val Phe His Leu Phe 3955 3960 3965 His Lys Leu Leu Ala Gly Gln Pro Leu Pro Ala Glu Met Thr Leu Ala 3970 3975 3980 Gln Leu Leu Thr Leu Leu Tyr Asp Arg Lys Leu Pro Gln Gly Tyr Arg 3985 3990 3995 4000 Ser Ile Asp Leu Thr Val Lys Leu Gly Ser Arg Val Ile Thr Asp Pro 4005 4010 4015 Ser Leu Ser Lys Thr Asp Ser Tyr Lys Arg Leu His Pro Glu Lys Asp 4020 4025 4030 His Gly Asp Leu Leu Ala Ser Cys Pro Glu Asp Glu Ala Leu Thr Pro 4035 4040 4045 Gly Asp Glu Cys Met Asp Gly Ile Leu Asp Glu Ser Leu Leu Glu Thr 4050 4055 4060 Cys Pro Ile Gln Ser Pro Leu Gln Val Phe Ala Gly Met Gly Gly Leu 4065 4070 4075 4080 Ala Leu Ile Ala Glu Arg Leu Pro Met Leu Tyr Pro Glu Val Ile Gln 4085 4090 4095 Gln Val Ser Ala Pro Val Val Thr Ser Thr Thr Gln Glu Lys Pro Lys 4100 4105 4110 Asp Ser Asp Gln Phe Glu Trp Val Thr Ile Glu Gln Ser Gly Glu Leu 4115 4120 4125 Val Tyr Glu Ala Pro Glu Thr Val Ala Ala Glu Pro Pro Ile Lys 4130 4135 4140 Ser Ala Val Gln Thr Met Ser Pro Ile Pro Ala His Ser Leu Ala Ala 4145 4150 4155 4160 Phe Gly Leu Phe Leu Arg Leu Pro Gly Tyr Ala Glu Val Leu Leu Lys 4165 4170 4175 Glu Arg Lys His Ala Gln Cys Leu Leu Arg Leu Val Leu Gly Val Thr 4180 4185 4190 Asp Asp Gly Glu Gly Ser His Ile Leu Gln Ser Pro Ser Ala Asn Val 4195 4200 4205 Leu Pro Thr Leu Pro Phe His Val Leu Arg Ser Leu Phe Ser Thr Thr 4210 4215 4220 Pro Leu Thr Thr Asp Asp Gly Val Leu Leu Arg Arg Met Ala Leu Glu 4225 4230 4235 4240 Ile Gly Ala Leu His Leu Ile Leu Val Cys Leu Ser Ala Leu Ser His 4245 4250 4255 His Ser Pro Arg Val Pro Asn Ser Ser Val Asn Gln Thr Glu Pro Gln 4260 4265 4270 Val Ser Ser Ser His Asn Pro Thr Ser Thr Glu Glu Gln Gln Leu Tyr 4275 4280 4285 Trp Ala Lys Gly Thr Gly Phe Gly Thr Gly Ser Thr Ala Ser Gly Trp 4290 4295 4300 Asp Val Glu Gln Ala Leu Thr Lys Gln Arg Leu Glu Glu His Val 4305 4310 4315 4320 Thr Cys Leu Leu Gln Val Leu Ala Ser Tyr Ile Asn Pro Val Ser Ser 4325 4330 4335 Ala Val Asn Gly Glu Ala Gln Ser Ser His Glu Thr Arg Gly Gln Asn 4340 4345 4350 Ser Asn Ala Leu Pro Ser Val Leu Leu Glu Leu Leu Ser Gln Ser Cys 4355 4360 4365 Leu Ile Pro Ala Met Ser Ser Tyr Leu Arg Asn Asp Ser Val Leu Asp 4370 4375 4380 Met Ala Arg His Val Pro Leu Tyr Arg Ala Leu Leu Glu Leu Leu Arg 4385 4390 4395 4400 Ala Ile Ala Ser Cys Ala Ala Met Val Pro Leu Leu Leu Pro Leu Ser 4405 4410 4415 Thr Glu Asn Gly Glu Glu Glu Glu Glu Gln Ser Glu Cys Gln Thr Ser 4420 4425 4430 Val Gly Thr Leu Leu Ala Lys Met Lys Thr Cys Val Asp Thr Tyr Thr 4435 4440 4445 Asn Arg Leu Arg Ser Lys Arg Glu Asn Val Lys Thr Gly Val Lys Pro 4450 4455 4460 Asp Ala Ser Asp Gln Glu Pro Glu Gly Leu Thr Leu Leu Val Pro Asp 4465 4470 4475 4480 Ile Gln Lys Thr Ala Glu Ile Val Tyr Ala Ala Thr Thr Ser Leu Arg 4485 4490 4495 Gln Ala Asn Gln Glu Lys Lys Leu Gly Glu Tyr Ser Lys Lys Ala Ala 4500 4505 4510 Met Lys Pro Lys Pro Leu Ser Val Leu Lys Ser Leu Glu Glu Lys Tyr 4515 4520 4525 Val Ala Val Met Lys Lys Leu Gln Phe Asp Thr Phe Glu Met Val Ser 4530 4535 4540 Glu Asp Glu Asp Gly Lys Leu Gly Phe Lys Val Asn Tyr His Tyr Met 4545 4550 4555 4560 Ser Gln Val Lys Asn Ala Asn Asp Ala Asn Ser Ala Ala Arg Ala Arg 4565 4570 4575 Arg Leu Ala Gln Glu Ala Val Thr Leu Ser Thr Ser Leu Pro Leu Ser 4580 4585 4590 Ser Ser Ser Ser Val Phe Val Arg Cys Asp Glu Glu Arg Leu Asp Ile 4595 4600 4605 Met Lys Val Leu Ile Thr Gly Pro Ala Asp Thr Pro Tyr Ala Asn Gly 4610 4615 4620 Cys Phe Glu Phe Asp Val Tyr Phe Pro Gln Asp Tyr Pro Ser Ser Pro 4625 4630 4635 4640 Pro Leu Val Asn Leu Glu Thr Thr Gly Gly His Ser Val Arg Phe Asn 4645 4650 4655 Pro Asn Leu Tyr Asn Asp Gly Lys Val Cys Leu Ser Ile Leu Asn Thr 4660 4665 4670 Trp His Gly Arg Pro Glu Glu Lys Trp Asn Pro Gln Thr Ser Ser Phe 4675 4680 4685 Leu Gln Val Leu Val Ser Val Gln Ser Leu Ile Leu Val Ala Glu Pro 4690 4695 4700 Tyr Phe Asn Glu Pro Gly Tyr Glu Arg Ser Arg Gly Thr Pro Ser Gly 4705 4710 4715 4720 Thr Gln Ser Ser Arg Glu Tyr Asp Gly Asn Ile Arg Gln Ala Thr Val 4725 4730 4735 Lys Trp Ala Met Leu Glu Gln Ile Arg Asn Pro Ser Pro Cys Phe Lys 4740 4745 4750 Glu Val Ile His Lys His Phe Tyr Leu Lys Arg Val Glu Ile Met Ala 4755 4760 4765 Gln Cys Glu Glu Trp Ile Ala Asp Ile Gln Gln Tyr Ser Ser Asp Lys 4770 4775 4780 Arg Val Gly Arg Thr Met Ser His His Ala Ala Ala Leu Lys Arg His 4785 4790 4795 4800 Thr Ala Gln Leu Arg Glu Glu Leu Leu Lys Leu Pro Cys Pro Glu Gly 4805 4810 4815 Leu Asp Pro Asp Thr Asp Asp Ala Pro Glu Val Cys Arg Ala Thr Thr 4820 4825 4830 Gly Ala Glu Glu Thr Leu Met His Asp Gln Val Lys Pro Ser Ser Ser Ser 4835 4840 4845 Lys Glu Leu Pro Ser Asp Phe Gln Leu 4850 4855 <210> 6 <211> 475 <212> PRT <213> Homo sapiens <400> 6 Met Ala Gly Arg Pro His Pro Tyr Asp Gly Asn Ser Ser Asp Pro Glu 1 5 10 15 Asn Trp Asp Arg Lys Leu His Ser Arg Pro Arg Lys Leu Tyr Lys His 20 25 30 Ser Ser Thr Ser Ser Arg Ile Ala Lys Gly Gly Val Asp His Thr Lys 35 40 45 Met Ser Leu His Gly Ala Ser Gly Gly His Glu Arg Ser Arg Asp Arg 50 55 60 Arg Arg Ser Ser Asp Arg Ser Arg Asp Ser Ser His Glu Arg Thr Glu 65 70 75 80 Ser Gln Leu Thr Pro Cys Ile Arg Asn Val Thr Ser Pro Thr Arg Gln 85 90 95 His His Val Glu Arg Glu Lys Asp His Ser Ser Ser Arg Pro Ser Ser 100 105 110 Pro Arg Pro Gln Lys Ala Ser Pro Asn Gly Ser Ile Ser Ser Ala Gly 115 120 125 Asn Ser Ser Arg Asn Ser Ser Gln Ser Ser Ser Asp Gly Ser Cys Lys 130 135 140 Thr Ala Gly Glu Met Val Phe Val Tyr Glu Asn Ala Lys Glu Gly Ala 145 150 155 160 Arg Asn Ile Arg Thr Ser Glu Arg Val Thr Leu Ile Val Asp Asn Thr 165 170 175 Arg Phe Val Val Asp Pro Ser Ile Phe Thr Ala Gln Pro Asn Thr Met 180 185 190 Leu Gly Arg Met Phe Gly Ser Gly Arg Glu His Asn Phe Thr Arg Pro 195 200 205 Asn Glu Lys Gly Glu Tyr Glu Val Ala Glu Gly Ile Gly Ser Thr Val 210 215 220 Phe Arg Ala Ile Leu Asp Tyr Tyr Lys Thr Gly Ile Ile Arg Cys Pro 225 230 235 240 Asp Gly Ile Ser Ile Pro Glu Leu Arg Glu Ala Cys Asp Tyr Leu Cys 245 250 255 Ile Ser Phe Glu Tyr Ser Thr Ile Lys Cys Arg Asp Leu Ser Ala Leu 260 265 270 Met His Glu Leu Ser Asn Asp Gly Ala Arg Arg Gln Phe Glu Phe Tyr 275 280 285 Leu Glu Glu Met Ile Leu Pro Leu Met Val Ala Ser Ala Gln Ser Gly 290 295 300 Glu Arg Glu Cys His Ile Val Val Leu Thr Asp Asp Asp Val Val Asp 305 310 315 320 Trp Asp Glu Glu Tyr Pro Pro Gln Met Gly Glu Glu Tyr Ser Gln Ile 325 330 335 Ile Tyr Ser Thr Lys Leu Tyr Arg Phe Phe Lys Tyr Ile Glu Asn Arg 340 345 350 Asp Val Ala Lys Ser Val Leu Lys Glu Arg Gly Leu Lys Lys Ile Arg 355 360 365 Leu Gly Ile Glu Gly Tyr Pro Thr Tyr Lys Glu Lys Val Lys Lys Arg 370 375 380 Pro Gly Gly Arg Pro Glu Val Ile Tyr Asn Tyr Val Gln Arg Pro Phe 385 390 395 400 Ile Arg Met Ser Trp Glu Lys Glu Glu Gly Lys Ser Arg His Val Asp 405 410 415 Phe Gln Cys Val Lys Ser Lys Ser Ile Thr Asn Leu Ala Ala Ala Ala 420 425 430 Ala Asp Ile Pro Gln Asp Gln Leu Val Val Met His Pro Thr Pro Gln 435 440 445 Val Asp Glu Leu Asp Ile Leu Pro Ile His Pro Pro Ser Gly Asn Ser 450 455 460 Asp Leu Asp Pro Asp Ala Gln Asn Pro Met Leu 465 470 475 <210> 7 <211> 1238 <212> PRT <213> Homo sapiens <400> 7 Met Gly Asp Ala Lys Glu Ala Gly Ala Glu Gly Pro Pro Ala Gly Ala 1 5 10 15 Ala Ala Arg Gly Gly Leu Ser Leu Leu Ser Gln Gly Glu Ser Glu Glu 20 25 30 Ser Ser Ala Gln Gly Ser Ala Leu Phe Leu Gly Gly Asn Glu Val Lys 35 40 45 Ser Arg Ala Val Val Lys Tyr Ser Ser Ala Pro Pro Arg Thr Ala Phe 50 55 60 Ala Arg Leu Glu Glu Lys Thr Asp Leu Lys Leu Pro Pro Ala Asn Trp 65 70 75 80 Leu Arg Glu Ser Ala Lys Leu Gly Pro Ala Gly Thr Thr Ile Leu Gly 85 90 95 Asn Ser Lys Lys Ser Lys Pro Phe Ser Ser Phe Gly Met Ala Tyr Asp 100 105 110 Phe Ile Asp Ser Val Gly Asn Asp Val Asp Val Val Ser Asp Ser Glu 115 120 125 Asn Ile Lys Lys Leu Leu Lys Ile Pro Tyr Ser Lys Ser His Val Ser 130 135 140 Met Ala Val His Arg Ile Gly Arg Thr Leu Leu Leu Asp Glu Leu Asp 145 150 155 160 Ile Gln Glu Leu Phe Met Arg Ser Ser Gln Thr Gly Asp Trp Thr Trp 165 170 175 Leu Lys Glu Phe Tyr Gln Arg Leu Ile Asp Gln Lys Trp Gln Arg Lys 180 185 190 Lys Lys Ser Lys Glu His Trp Tyr Gln Lys Ala Ile Leu Ser Lys Phe 195 200 205 Leu Tyr Tyr Ser Ile Asn Gly Asp Gly Ala Ala Gln Pro Val Ser Ser 210 215 220 Thr Ala Glu Gln Gln Glu Ser Ser Ser Ser Asp Gln Thr Asn Asp Ser 225 230 235 240 Glu Gly Ala Ser Trp Pro Ala Pro Phe Glu Met Pro Ser Ser Val Ser 245 250 255 Glu Asp Pro Ser Ala Ser Ser Gln Gly Ser Glu Pro Leu Glu Pro Ser 260 265 270 Tyr Ile Val Gly His Val Ala Ser Ala Pro Lys Glu Gln Asn Leu Ile 275 280 285 Thr Leu Phe Asn Asp Gly Glu His Ser Gin Gly Leu Lys Asn Asp Phe 290 295 300 Val Arg Asn Ile Leu Trp Thr Phe Glu Asp Ile His Met Leu Val Gly 305 310 315 320 Ser Asn Met Pro Ile Phe Gly Gly Gly Arg Tyr Pro Ala Val Ser Leu 325 330 335 Arg Leu Arg Asp Asn Asn Lys Pro Ile Asn Val Leu Thr Gly Ile Asp 340 345 350 Tyr Trp Leu Asp Asn Leu Ile Cys Asn Val Pro Glu Leu Val Met Cys 355 360 365 Phe His Val Asn Gly Ile Val Gln Lys Tyr Glu Met Ile Lys Thr Glu 370 375 380 Glu Ile Pro Asn Leu Glu Asn Ser Asn Phe Ser Thr Lys Val Ile Lys 385 390 395 400 Asp Ile Ala Gln Asn Ile Leu Ser Phe Leu Lys Ser Asn Cys Thr Lys 405 410 415 Glu Gly His Thr Tyr Trp Leu Phe Lys Ala Ser Gly Ser Asp Ile Val 420 425 430 Lys Leu Tyr Asp Leu Thr Thr Leu Cys Glu Glu Thr Glu Asp Lys Tyr 435 440 445 Gln Asn Pro Phe Thr Met Pro Val Ala Ile Leu Leu Tyr Lys Val Ala 450 455 460 Cys Asn Met Met Met Met Lys Lys Asn Gln Asn Lys Lys His Tyr Gly Thr 465 470 475 480 Ile Arg Thr Leu Leu Leu Asn Cys Leu Lys Leu Leu Asp Lys Ser Arg 485 490 495 His Pro Gln Ile Ile Ala Ser Ala Asn Tyr Met Leu Ser Glu Leu Phe 500 505 510 Gln Leu Asp Glu Pro Lys Lys Glu Glu Asn Ser Glu Ser Pro Leu Asn 515 520 525 Glu Asn Ser Asp Glu Ser Tyr Ser Glu Glu Glu Glu Glu Met Pro Asp 530 535 540 Ser Asp Glu Asn Gly Ser Tyr Ser Thr Ser Ser Asp Pro Ser Asp Asp 545 550 555 560 Ser Lys Ala Val Ala Ile Ile Lys Ser Val Gly Glu Leu Ser Val Pro 565 570 575 Glu Lys Tyr Lys Ser Ile His Gln Ile Arg Pro Ser Cys Ala Phe Pro 580 585 590 Val Cys His Asp Thr Glu Glu Arg Cys Arg Leu Val Leu Ser Tyr Val 595 600 605 Leu Glu Gly Leu Lys Ser Val Asp Ser Ser Ile Lys Lys Glu Ser Asp 610 615 620 Leu Pro Ala Ala Asp Pro Ser Thr Pro Ile Pro Leu Lys Tyr Glu Asp 625 630 635 640 Glu Ser Ser Arg Gly Gly Pro Glu Gly Leu Glu Lys Gln Met Ala Leu 645 650 655 Phe Leu Asp Lys Met Gly Ser Leu Gln Lys Gly Asn Tyr Ser Ser Gln 660 665 670 Ser Gly Met Ile Pro Gly Ser Trp Gln His Lys Met Lys Leu Gln Leu 675 680 685 Ile Leu Lys Ser Ser Lys Ala Tyr Tyr Val Leu Ser Asp Ala Ala Met 690 695 700 Ser Leu Gln Lys Tyr Gly Arg Ala Leu Arg Tyr Ile Lys Leu Ala Leu 705 710 715 720 Gln Ser His Asp Thr Tyr Cys Cys Leu Cys Thr Asn Met Leu Ser Glu 725 730 735 Val Leu Leu Phe Leu Ser Gln Tyr Leu Thr Leu Cys Gly Asp Ile Gln 740 745 750 Leu Met Leu Ala Gln Asn Ala Asn Asn Arg Ala Ala His Leu Glu Glu 755 760 765 Phe His Tyr Gln Thr Lys Glu Asp Gln Glu Ile Leu His Ser Leu His 770 775 780 Arg Glu Ser Ser Cys Gin Gly Phe Ala Trp Ala Thr Asp Leu Ser Thr 785 790 795 800 Asp Leu Glu Ser Gln Leu Ser Val Ser Cys Lys Cys Tyr Glu Ala Ala 805 810 815 Asn Glu Ile Leu Gln Phe Ser Asp Leu Lys Ser Gln Asn Pro Glu His 820 825 830 Tyr Val Gln Val Leu Lys Arg Met Gly Asn Ile Arg Asn Glu Ile Gly 835 840 845 Val Phe Tyr Met Asn Gln Ala Ala Ala Leu Gln Ser Glu Arg Leu Val 850 855 860 Ser Lys Ser Val Ser Ala Ala Glu Gln Gln Leu Trp Lys Lys Ser Phe 865 870 875 880 Ser Cys Phe Glu Lys Gly Ile His Asn Phe Glu Ser Ile Glu Asp Ala 885 890 895 Thr Asn Ala Ala Leu Leu Leu Cys Asn Thr Gly Arg Leu Met Arg Ile 900 905 910 Cys Ala Gln Ala His Cys Gly Ala Gly Asp Glu Leu Lys Arg Glu Phe 915 920 925 Ser Pro Glu Glu Gly Leu Tyr Tyr Asn Lys Ala Ile Asp Tyr Tyr Leu 930 935 940 Lys Ala Leu Arg Ser Leu Gly Thr Arg Asp Ile His Pro Ala Val Trp 945 950 955 960 Asp Ser Val Asn Trp Glu Leu Ser Thr Thr Tyr Phe Thr Met Ala Thr 965 970 975 Leu Gln Gln Asp Tyr Ala Pro Leu Ser Arg Lys Ala Gln Glu Gln Ile 980 985 990 Glu Lys Glu Val Ser Glu Ala Met Met Lys Ser Leu Lys Tyr Cys Asp 995 1000 1005 Val Asp Ser Val Ser Ala Arg Gln Pro Leu Cys Gln Tyr Arg Ala Ala 1010 1015 1020 Thr Ile His His Arg Leu Ala Ser Met Tyr His Ser Cys Leu Arg Asn 1025 1030 1035 1040 Gln Val Gly Asp Glu His Leu Arg Lys Gln His Arg Val Leu Ala Asp 1045 1050 1055 Leu His Tyr Ser Lys Ala Ala Lys Leu Phe Gln Leu Leu Lys Asp Ala 1060 1065 1070 Pro Cys Glu Leu Leu Arg Val Gln Leu Glu Arg Val Ala Phe Ala Glu 1075 1080 1085 Phe Gln Met Thr Ser Gln Asn Ser Asn Val Gly Lys Leu Lys Thr Leu 1090 1095 1100 Ser Gly Ala Leu Asp Ile Met Val Arg Thr Glu His Ala Phe Gln Leu 1105 1110 1115 1120 Ile Gln Lys Glu Leu Ile Glu Glu Phe Gly Gln Pro Lys Ser Gly Asp 1125 1130 1135 Ala Ala Ala Ala Ala Asp Ala Ser Pro Ser Leu Asn Arg Glu Glu Val 1140 1145 1150 Met Lys Leu Leu Ser Ile Phe Glu Ser Arg Leu Ser Phe Leu Leu Leu 1155 1160 1165 Gln Ser Ile Lys Leu Leu Ser Ser Thr Lys Lys Lys Thr Ser Asn Asn 1170 1175 1180 Ile Glu Asp Asp Thr Ile Leu Lys Thr Asn Lys His Ile Tyr Ser Gln 1185 1190 1195 1200 Leu Leu Arg Ala Thr Ala Asn Lys Thr Ala Thr Leu Leu Glu Arg Ile 1205 1210 1215 Asn Val Ile Val His Leu Leu Gly Gln Leu Ala Ala Gly Ser Ala Ala 1220 1225 1230 Ser Ser Asn Ala Val Gln 1235 <210> 8 <211> 578 <212> PRT <213> Homo sapiens <400> 8 Met Leu Leu Leu Ile Asn Val Ile Leu Thr Leu Trp Val Ser Cys Ala 1 5 10 15 Asn Gly Gln Glu Val Lys Pro Cys Asp Phe Pro Glu Ile Gln His Gly 20 25 30 Gly Leu Tyr Tyr Lys Ser Leu Arg Arg Leu Tyr Phe Pro Ala Ala Ala 35 40 45 Gly Gln Ser Tyr Ser Tyr Tyr Cys Asp Gln Asn Phe Val Thr Pro Ser 50 55 60 Gly Ser Tyr Trp Asp Tyr Ile His Cys Thr Gln Asp Gly Trp Ser Pro 65 70 75 80 Thr Val Pro Cys Leu Arg Thr Cys Ser Lys Ser Asp Val Glu Ile Glu 85 90 95 Asn Gly Phe Ile Ser Glu Ser Ser Ser Ile Tyr Ile Leu Asn Glu Glu 100 105 110 Thr Gln Tyr Asn Cys Lys Pro Gly Tyr Ala Thr Ala Glu Gly Asn Ser 115 120 125 Ser Gly Ser Ile Thr Cys Leu Gln Asn Gly Trp Ser Thr Gln Pro Ile 130 135 140 Cys Ile Lys Phe Cys Asp Met Pro Val Phe Glu Asn Ser Arg Ala Lys 145 150 155 160 Ser Asn Gly Met Trp Phe Lys Leu His Asp Thr Leu Asp Tyr Glu Cys 165 170 175 Tyr Asp Gly Tyr Glu Ser Ser Tyr Gly Asn Thr Thr Asp Ser Ile Val 180 185 190 Cys Gly Glu Asp Gly Trp Ser His Leu Pro Thr Cys Tyr Asn Ser Ser 195 200 205 Glu Asn Cys Gly Pro Pro Pro Pro Ile Ser Asn Gly Asp Thr Thr Ser 210 215 220 Phe Pro Gln Lys Val Tyr Leu Pro Trp Ser Arg Val Glu Tyr Gln Cys 225 230 235 240 Gln Ser Tyr Tyr Glu Leu Gin Gly Ser Lys Tyr Val Thr Cys Ser Asn 245 250 255 Gly Asp Trp Ser Glu Pro Pro Arg Cys Ile Ser Met Lys Pro Cys Glu 260 265 270 Phe Pro Glu Ile Gln His Gly His Leu Tyr Tyr Glu Asn Thr Arg Arg 275 280 285 Pro Tyr Phe Pro Val Ala Thr Gly Gln Ser Tyr Ser Tyr Tyr Cys Asp 290 295 300 Gln Asn Phe Val Thr Pro Ser Gly Ser Tyr Trp Asp Tyr Ile His Cys 305 310 315 320 Thr Gln Asp Gly Trp Leu Pro Thr Val Pro Cys Leu Arg Thr Cys Ser 325 330 335 Lys Ser Asp Ile Glu Ile Glu Asn Gly Phe Ile Ser Glu Ser Ser Ser Ser 340 345 350 Ile Tyr Ile Leu Asn Lys Glu Ile Gln Tyr Lys Cys Lys Pro Gly Tyr 355 360 365 Ala Thr Ala Asp Gly Asn Ser Ser Gly Ser Ile Thr Cys Leu Gln Asn 370 375 380 Gly Trp Ser Ala Gln Pro Ile Cys Ile Lys Phe Cys Asp Met Pro Val 385 390 395 400 Phe Glu Asn Ser Arg Ala Lys Ser Asn Gly Met Arg Phe Lys Leu His 405 410 415 Asp Thr Leu Asp Tyr Glu Cys Tyr Asp Gly Tyr Glu Ile Ser Tyr Gly 420 425 430 Asn Thr Thr Gly Ser Ile Val Cys Gly Glu Asp Gly Trp Ser His Phe 435 440 445 Pro Thr Cys Tyr Asn Ser Ser Glu Lys Cys Gly Pro Pro Pro Pro Ile 450 455 460 Ser Asn Gly Asp Thr Thr Ser Phe Leu Leu Lys Val Tyr Val Pro Gln 465 470 475 480 Ser Arg Val Glu Tyr Gln Cys Gln Ser Tyr Tyr Glu Leu Gln Gly Ser 485 490 495 Asn Tyr Val Thr Cys Ser Asn Gly Glu Trp Ser Glu Pro Pro Arg Cys 500 505 510 Ile His Pro Cys Ile Ile Thr Glu Glu Asn Met Asn Lys Asn Asn Ile 515 520 525 Gln Leu Lys Gly Lys Ser Asp Ile Lys Tyr Tyr Ala Lys Thr Gly Asp 530 535 540 Thr Ile Glu Phe Met Cys Lys Leu Gly Tyr Asn Ala Asn Thr Ser Val 545 550 555 560 Leu Ser Phe Gln Ala Val Cys Arg Glu Gly Ile Val Glu Tyr Pro Arg 565 570 575 Cys Glu <210> 9 <211> 586 <212> PRT <213> Homo sapiens <400> 9 Met Ser Val His Gln Ile Arg Lys His Ala Val Leu Pro Pro Ile Ile 1 5 10 15 Cys Arg Ser Asp Lys Glu Phe Leu Glu Ser Val Gln Arg Tyr Ile Ile 20 25 30 Thr Glu Thr Glu Arg Leu Gly Cys Ser Glu Glu Gly Pro Ala Asp Glu 35 40 45 Tyr Tyr Ile Ile Tyr Arg Asn Val Phe Asp Lys Val Ile Glu His Ile 50 55 60 Thr Ala Tyr Lys Ser Ile Leu Thr Ser Ile Lys Lys Glu Tyr Asp Ala 65 70 75 80 Phe Ile Glu Thr Ile Lys Lys Asp Arg Arg Thr Thr Phe Cys Leu His 85 90 95 Gly Lys Leu Lys Gly Leu Ala Ala Glu Pro Thr Ala Leu Val Tyr Tyr 100 105 110 Arg Lys Arg Thr Ile Gln Leu Glu Ala Lys Met Arg Ile Ile Glu Ser 115 120 125 Asn Ser Ser Lys Ile Gln Ser Gln Ile Asp His Ile Lys Gln Cys Arg 130 135 140 Ala Glu Tyr Asp Thr Lys Glu Val Lys Tyr Cys Thr Phe Ser Lys Asp 145 150 155 160 Pro Ser Lys Pro Ile Pro Gly Met Thr Leu Gln Glu Ser Met Asn Leu 165 170 175 Asp Ala Leu Thr Lys Tyr Met Lys His Leu Glu Asp Lys Tyr Ala Glu 180 185 190 Ile Lys Gln Ala Met Leu Ile Lys Tyr Val Pro Ala Gln Arg Lys Ala 195 200 205 Asp Leu Asp Glu Glu Met Ile Val Leu Leu Lys Arg Arg Asp Val Ala 210 215 220 Glu Asn Leu Asn Lys Lys Leu Gln Phe Cys His Gln Arg Leu Gln Ile 225 230 235 240 Ile Ser Gln Ala Leu Ser Ser Ser Trp Val Lys Ser Asp Met Ser Ser Pro 245 250 255 Phe Gln Asp Phe Val Glu Gln Ile Gln Lys Thr Lys Tyr Leu Gln Gly 260 265 270 Asp Gln Gly Ile Val Glu Glu Leu Met Glu Asp Asp Pro Arg Arg Ala 275 280 285 Lys Glu Ala Glu Ile Met Leu His Tyr Ile Glu Arg Phe Asn Glu Leu 290 295 300 Ile Ser Leu Gly Glu Tyr Glu Lys Ala Ala Cys Tyr Ala Ala Asn Ser 305 310 315 320 Pro Arg Arg Ile Leu Arg Asn Ile Gly Thr Met Asn Thr Phe Lys Ala 325 330 335 Val Gly Lys Ile Arg Gly Lys Pro Leu Pro Leu Leu Leu Leu Phe Phe Glu 340 345 350 Ala Leu Phe Ile Thr Ser His Ala Phe Pro Cys Pro Val Asp Ala Ala 355 360 365 Leu Thr Leu Glu Gly Ile Lys Cys Gly Leu Ser Glu Lys Arg Leu Asp 370 375 380 Leu Val Thr Asn Trp Val Thr Gln Glu Arg Leu Thr Phe Ser Glu Glu 385 390 395 400 Ala Gly Asp Val Ile Cys Asp Tyr Gly Glu Gln Asp Thr Tyr Asn Lys 405 410 415 Ala Lys Cys Leu Ala Leu Ala Gln Ile Val Tyr Ser Glu Cys Gly Leu 420 425 430 His Lys Lys Ala Ile Leu Cys Leu Cys Lys Gln Gly Gln Thr His Arg 435 440 445 Val Met Glu Tyr Ile Gln Gln Leu Lys Asp Phe Thr Thr Asp Asp Leu 450 455 460 Leu Gln Leu Leu Met Ser Cys Pro Gln Val Glu Leu Ile Gln Cys Leu 465 470 475 480 Thr Lys Glu Leu Asn Glu Lys Gln Pro Ser Leu Ser Phe Gly Leu Ala 485 490 495 Ile Leu His Leu Phe Ser Ala Asp Met Lys Lys Val Gly Ile Lys Leu 500 505 510 Leu Gln Glu Ile Asn Lys Gly Gly Ile Asp Ala Val Glu Ser Leu Met 515 520 525 Ile Asn Asp Ser Phe Cys Ser Ile Glu Lys Trp Gln Glu Val Ala Asn 530 535 540 Ile Cys Ser Gln Asn Gly Phe Asp Lys Leu Ser Asn Asp Ile Thr Ser 545 550 555 560 Ile Leu Arg Ser Gln Ala Ala Val Thr Glu Ile Ser Glu Glu Asp Asp 565 570 575 Ala Val Asn Leu Met Glu His Val Phe Trp 580 585 <210> 10 <211> 968 <212> PRT <213> Homo sapiens <400> 10 Met Asp Asp Ser Glu Val Glu Ser Thr Ala Ser Ile Leu Ala Ser Val 1 5 10 15 Lys Glu Gln Glu Ala Gln Phe Glu Lys Leu Thr Arg Ala Leu Glu Glu 20 25 30 Glu Arg Arg His Val Ser Ala Gln Leu Glu Arg Val Arg Val Ser Pro 35 40 45 Gln Asp Ala Asn Pro Leu Met Ala Asn Gly Thr Leu Thr Arg Arg His 50 55 60 Gln Asn Gly Arg Phe Val Gly Asp Ala Asp Leu Glu Arg Gln Lys Phe 65 70 75 80 Ser Asp Leu Lys Leu Asn Gly Pro Gln Asp His Ser His Leu Leu Tyr 85 90 95 Ser Thr Ile Pro Arg Met Gln Glu Pro Gly Gln Ile Val Glu Thr Tyr 100 105 110 Thr Glu Glu Asp Pro Glu Gly Ala Met Ser Val Val Ser Val Glu Thr 115 120 125 Ser Asp Asp Gly Thr Thr Arg Arg Thr Glu Thr Thr Val Lys Lys Val 130 135 140 Val Lys Thr Val Thr Thr Arg Thr Val Gln Pro Val Ala Met Gly Pro 145 150 155 160 Asp Gly Leu Pro Val Asp Ala Ser Ser Val Ser Asn Asn Tyr Ile Gln 165 170 175 Thr Leu Gly Arg Asp Phe Arg Lys Asn Gly Asn Gly Gly Pro Gly Pro 180 185 190 Tyr Val Gly Gln Ala Gly Thr Ala Thr Leu Pro Arg Asn Phe His Tyr 195 200 205 Pro Pro Asp Gly Tyr Ser Arg His Tyr Glu Asp Gly Tyr Pro Gly Gly 210 215 220 Ser Asp Asn Tyr Gly Ser Leu Ser Arg Val Thr Arg Ile Glu Glu Arg 225 230 235 240 Tyr Arg Pro Ser Met Glu Gly Tyr Arg Ala Pro Ser Arg Gln Asp Val 245 250 255 Tyr Gly Pro Gln Pro Gln Val Arg Val Gly Gly Ser Ser Val Asp Leu 260 265 270 His Arg Phe His Pro Glu Pro Tyr Gly Leu Glu Asp Asp Gln Arg Ser 275 280 285 Met Gly Tyr Asp Asp Leu Asp Tyr Gly Met Met Ser Asp Tyr Gly Thr 290 295 300 Ala Arg Arg Thr Gly Thr Pro Ser Asp Pro Arg Arg Arg Leu Arg Ser 305 310 315 320 Tyr Glu Asp Met Ile Gly Glu Glu Val Pro Ser Asp Gln Tyr Tyr Trp 325 330 335 Ala Pro Leu Ala Gln His Glu Arg Gly Ser Leu Ala Ser Leu Asp Ser 340 345 350 Leu Arg Lys Gly Gly Pro Pro Pro Asn Trp Arg Gln Pro Glu Leu 355 360 365 Pro Glu Val Ile Ala Met Leu Gly Phe Arg Leu Asp Ala Val Lys Ser 370 375 380 Asn Ala Ala Ala Tyr Leu Gln His Leu Cys Tyr Arg Asn Asp Lys Val 385 390 395 400 Lys Thr Asp Val Arg Lys Leu Lys Gly Ile Pro Val Leu Val Gly Leu 405 410 415 Leu Asp His Pro Lys Lys Glu Val His Leu Gly Ala Cys Gly Ala Leu 420 425 430 Lys Asn Ile Ser Phe Gly Arg Asp Gln Asp Asn Lys Ile Ala Ile Lys 435 440 445 Asn Cys Asp Gly Val Pro Ala Leu Val Arg Leu Leu Arg Lys Ala Arg 450 455 460 Asp Met Asp Leu Thr Glu Val Ile Thr Gly Thr Leu Trp Asn Leu Ser 465 470 475 480 Ser His Asp Ser Ile Lys Met Glu Ile Val Asp His Ala Leu His Ala 485 490 495 Leu Thr Asp Glu Val Ile Ile Pro His Ser Gly Trp Glu Arg Glu Pro 500 505 510 Asn Glu Asp Cys Lys Pro Arg His Ile Glu Trp Glu Ser Val Leu Thr 515 520 525 Asn Thr Ala Gly Cys Leu Arg Asn Val Ser Ser Glu Arg Ser Glu Ala 530 535 540 Arg Arg Lys Leu Arg Glu Cys Asp Gly Leu Val Asp Ala Leu Ile Phe 545 550 555 560 Ile Val Gln Ala Glu Ile Gly Gln Lys Asp Ser Asp Ser Lys Leu Val 565 570 575 Glu Asn Cys Val Cys Leu Leu Arg Asn Leu Ser Tyr Gln Val His Arg 580 585 590 Glu Ile Pro Gln Ala Glu Arg Tyr Gln Glu Ala Ala Pro Asn Val Ala 595 600 605 Asn Asn Thr Gly Pro His Ala Ala Ser Cys Phe Gly Ala Lys Lys Gly 610 615 620 Lys Asp Glu Trp Phe Ser Arg Gly Lys Lys Pro Ile Glu Asp Pro Ala 625 630 635 640 Asn Asp Thr Val Asp Phe Pro Lys Arg Thr Ser Pro Ala Arg Gly Tyr 645 650 655 Glu Leu Leu Phe Gln Pro Glu Val Val Arg Ile Tyr Ile Ser Leu Leu 660 665 670 Lys Glu Ser Lys Thr Pro Ala Ile Leu Glu Ala Ser Ala Gly Ala Ile 675 680 685 Gln Asn Leu Cys Ala Gly Arg Trp Thr Tyr Gly Arg Tyr Ile Arg Ser 690 695 700 Ala Leu Arg Gln Glu Lys Ala Leu Ser Ala Ile Ala Asp Leu Leu Thr 705 710 715 720 Asn Glu His Glu Arg Val Val Lys Ala Ala Ser Gly Ala Leu Arg Asn 725 730 735 Leu Ala Val Asp Ala Arg Asn Lys Glu Leu Ile Gly Lys His Ala Ile 740 745 750 Pro Asn Leu Val Lys Asn Leu Pro Gly Gly Gln Gln Asn Ser Ser Trp 755 760 765 Asn Phe Ser Glu Asp Thr Val Ile Ser Ile Leu Asn Thr Ile Asn Glu 770 775 780 Val Ile Ala Glu Asn Leu Glu Ala Ala Lys Lys Leu Arg Glu Thr Gln 785 790 795 800 Gly Ile Glu Lys Leu Val Leu Ile Asn Lys Ser Gly Asn Arg Ser Glu 805 810 815 Lys Glu Val Arg Ala Ala Ala Leu Val Leu Gln Thr Ile Trp Gly Tyr 820 825 830 Lys Glu Leu Arg Lys Pro Leu Glu Lys Glu Gly Trp Lys Lys Ser Asp 835 840 845 Phe Gln Val Asn Leu Asn Asn Ala Ser Arg Ser Gln Ser Ser His Ser 850 855 860 Tyr Asp Asp Ser Thr Leu Pro Leu Ile Asp Arg Asn Gln Lys Ser Asp 865 870 875 880 Lys Lys Pro Asp Arg Glu Glu Ile Gln Met Ser Asn Met Gly Ser Asn 885 890 895 Thr Lys Ser Leu Asp Asn Asn Tyr Ser Thr Pro Asn Glu Arg Gly Asp 900 905 910 His Asn Arg Thr Leu Asp Arg Ser Gly Asp Leu Gly Asp Met Glu Pro 915 920 925 Leu Lys Gly Thr Thr Pro Leu Met Gln Asp Glu Gly Gln Glu Ser Leu 930 935 940 Glu Glu Glu Leu Asp Val Leu Val Leu Asp Asp Glu Gly Gly Gln Val 945 950 955 960 Ser Tyr Pro Ser Met Gln Lys Ile 965 <210> 11 <211> 495 <212> PRT <213> Homo sapiens <400> 11 Met Asn Lys Ser Arg Trp Gln Ser Arg Arg Arg His Gly Arg Arg Ser 1 5 10 15 His Gln Gln Asn Pro Trp Phe Arg Leu Arg Asp Ser Glu Asp Arg Ser 20 25 30 Asp Ser Arg Ala Ala Gln Pro Ala His Asp Ser Gly His Gly Asp Asp 35 40 45 Glu Ser Pro Ser Thr Ser Ser Gly Thr Ala Gly Thr Ser Ser Val Pro 50 55 60 Glu Leu Pro Gly Phe Tyr Phe Asp Pro Glu Lys Lys Arg Tyr Phe Arg 65 70 75 80 Leu Leu Pro Gly His Asn Asn Cys Asn Pro Leu Thr Lys Glu Ser Ile 85 90 95 Arg Gln Lys Glu Met Glu Ser Lys Arg Leu Arg Leu Leu Gln Glu Glu 100 105 110 Asp Arg Arg Lys Lys Ile Ala Arg Met Gly Phe Asn Ala Ser Ser Met 115 120 125 Leu Arg Lys Ser Gln Leu Gly Phe Leu Asn Val Thr Asn Tyr Cys His 130 135 140 Leu Ala His Glu Leu Arg Leu Ser Cys Met Glu Arg Lys Lys Val Gln 145 150 155 160 Ile Arg Ser Met Asp Pro Ser Ala Leu Ala Ser Asp Arg Phe Asn Leu 165 170 175 Ile Leu Ala Asp Thr Asn Ser Asp Arg Leu Phe Thr Val Asn Asp Val 180 185 190 Lys Val Gly Gly Ser Lys Tyr Gly Ile Ile Asn Leu Gln Ser Leu Lys 195 200 205 Thr Pro Thr Leu Lys Val Phe Met His Glu Asn Leu Tyr Phe Thr Asn 210 215 220 Arg Lys Val Asn Ser Val Cys Trp Ala Ser Leu Asn His Leu Asp Ser 225 230 235 240 His Ile Leu Leu Cys Leu Met Gly Leu Ala Glu Thr Pro Gly Cys Ala 245 250 255 Thr Leu Leu Pro Ala Ser Leu Phe Val Asn Ser His Pro Gly Ile Asp 260 265 270 Arg Pro Gly Met Leu Cys Ser Phe Arg Ile Pro Gly Ala Trp Ser Cys 275 280 285 Ala Trp Ser Leu Asn Ile Gln Ala Asn Asn Cys Phe Ser Thr Gly Leu 290 295 300 Ser Arg Arg Val Leu Leu Thr Asn Val Val Thr Gly His Arg Gln Ser 305 310 315 320 Phe Gly Thr Asn Ser Asp Val Leu Ala Gln Gln Phe Ala Leu Met Ala 325 330 335 Pro Leu Leu Phe Asn Gly Cys Arg Ser Gly Glu Ile Phe Ala Ile Asp 340 345 350 Leu Arg Cys Gly Asn Gln Gly Lys Gly Trp Lys Ala Thr Arg Leu Phe 355 360 365 His Asp Ser Ala Val Thr Ser Val Arg Ile Leu Gln Asp Glu Gln Tyr 370 375 380 Leu Met Ala Ser Asp Met Ala Gly Lys Ile Lys Leu Trp Asp Leu Arg 385 390 395 400 Thr Thr Lys Cys Val Arg Gln Tyr Glu Gly His Val Asn Glu Tyr Ala 405 410 415 Tyr Leu Pro Leu His Val His Glu Glu Glu Gly Ile Leu Val Ala Val 420 425 430 Gly Gln Asp Cys Tyr Thr Arg Ile Trp Ser Leu His Asp Ala Arg Leu 435 440 445 Leu Arg Thr Ile Pro Ser Pro Tyr Pro Ala Ser Lys Ala Asp Ile Pro 450 455 460 Ser Val Ala Phe Ser Ser Arg Leu Gly Gly Ser Arg Gly Ala Pro Gly 465 470 475 480 Leu Leu Met Ala Val Gly Gln Asp Leu Tyr Cys Tyr Ser Tyr Ser 485 490 495 <210> 12 <211> 1157 <212> PRT <213> Homo sapiens <400> 12 Met Gly Lys Leu Arg Arg Arg Tyr Asn Ile Lys Gly Arg Gln Gln Ala 1 5 10 15 Gly Pro Gly Pro Ser Lys Gly Pro Pro Glu Pro Pro Val Gln Leu 20 25 30 Glu Leu Glu Asp Lys Asp Thr Leu Lys Gly Val Asp Ala Ser Asn Ala 35 40 45 Leu Val Leu Pro Gly Lys Lys Lys Lys Lys Lys Thr Lys Ala Pro Leu 50 55 60 Ser Lys Lys Glu Lys Lys Pro Leu Thr Lys Lys Glu Lys Lys Val Leu 65 70 75 80 Gln Lys Ile Leu Glu Gln Lys Glu Lys Lys Ser Gln Arg Ala Glu Met 85 90 95 Leu Gln Lys Leu Ser Glu Val Gln Ala Ser Glu Ala Glu Met Arg Leu 100 105 110 Phe Tyr Thr Thr Ser Lys Leu Gly Thr Gly Asn Arg Met Tyr His Thr 115 120 125 Lys Glu Lys Ala Asp Glu Val Val Ala Pro Gly Gln Glu Lys Ile Ser 130 135 140 Ser Leu Ser Gly Ala His Arg Lys Arg Arg Arg Trp Pro Ser Ala Glu 145 150 155 160 Glu Glu Glu Glu Glu Glu Glu Glu Glu Ser Glu Ser Glu Leu Glu Glu Glu 165 170 175 Ser Glu Leu Asp Glu Asp Pro Ala Ala Glu Pro Ala Glu Ala Gly Val 180 185 190 Gly Thr Thr Val Ala Pro Leu Pro Pro Ala Pro Ala Pro Ser Ser Gln 195 200 205 Pro Val Pro Ala Gly Met Thr Val Pro Pro Pro Ala Ala Ala Pro 210 215 220 Pro Leu Pro Arg Ala Leu Ala Lys Pro Ala Val Phe Ile Pro Val Asn 225 230 235 240 Arg Ser Pro Glu Met Gln Glu Glu Arg Leu Lys Leu Pro Ile Leu Ser 245 250 255 Glu Glu Gln Val Ile Met Glu Ala Val Ala Glu His Pro Ile Val Ile 260 265 270 Val Cys Gly Glu Thr Gly Ser Gly Lys Thr Thr Gln Val Pro Gln Phe 275 280 285 Leu Tyr Glu Ala Gly Phe Ser Ser Glu Asp Ser Ile Ile Gly Val Thr 290 295 300 Glu Pro Arg Arg Val Ala Ala Val Ala Met Ser Gln Arg Val Ala Lys 305 310 315 320 Glu Met Asn Leu Ser Gln Arg Val Val Ser Tyr Gln Ile Arg Tyr Glu 325 330 335 Gly Asn Val Thr Glu Glu Thr Arg Ile Lys Phe Met Thr Asp Gly Val 340 345 350 Leu Leu Lys Glu Ile Gln Lys Asp Phe Leu Leu Leu Arg Tyr Lys Val 355 360 365 Val Ile Ile Asp Glu Ala His Glu Arg Ser Val Tyr Thr Asp Ile Leu 370 375 380 Ile Gly Leu Leu Ser Arg Ile Val Thr Leu Arg Ala Lys Arg Asn Leu 385 390 395 400 Pro Leu Lys Leu Leu Ile Met Ser Ala Thr Leu Arg Val Glu Asp Phe 405 410 415 Thr Gln Asn Pro Arg Leu Phe Ala Lys Pro Pro Pro Val Ile Lys Val 420 425 430 Glu Ser Arg Gln Phe Pro Val Thr Val His Phe Asn Lys Arg Thr Pro 435 440 445 Leu Glu Asp Tyr Ser Gly Glu Cys Phe Arg Lys Val Cys Lys Ile His 450 455 460 Arg Met Leu Pro Ala Gly Gly Ile Leu Val Phe Leu Thr Gly Gln Ala 465 470 475 480 Glu Val His Ala Leu Cys Arg Arg Leu Arg Lys Ala Phe Pro Ser 485 490 495 Arg Ala Arg Pro Gln Glu Lys Asp Asp Asp Gln Lys Asp Ser Val Glu 500 505 510 Glu Met Arg Lys Phe Lys Lys Ser Arg Ala Arg Ala Lys Lys Ala Arg 515 520 525 Ala Glu Val Leu Pro Gln Ile Asn Leu Asp His Tyr Ser Val Leu Pro 530 535 540 Ala Gly Glu Gly Asp Glu Asp Arg Glu Ala Glu Val Asp Glu Glu Glu 545 550 555 560 Gly Ala Leu Asp Ser Asp Leu Asp Leu Asp Leu Gly Asp Gly Gly Gln 565 570 575 Asp Gly Gly Glu Gln Pro Asp Ala Ser Leu Pro Leu His Val Leu Pro 580 585 590 Leu Tyr Ser Leu Leu Ala Pro Glu Lys Gln Ala Gln Val Phe Lys Pro 595 600 605 Pro Pro Glu Gly Thr Arg Leu Cys Val Val Ala Thr Asn Val Ala Glu 610 615 620 Thr Ser Leu Thr Ile Pro Gly Ile Lys Tyr Val Val Asp Cys Gly Lys 625 630 635 640 Val Lys Lys Arg Tyr Tyr Asp Arg Val Thr Gly Val Ser Ser Phe Arg 645 650 655 Val Thr Trp Val Ser Gln Ala Ser Ala Asp Gln Arg Ala Gly Arg Ala 660 665 670 Gly Arg Thr Glu Pro Gly His Cys Tyr Arg Leu Tyr Ser Ser Ala Val 675 680 685 Phe Gly Asp Phe Glu Gln Phe Pro Pro Glu Ile Thr Arg Arg Pro 690 695 700 Val Glu Asp Leu Ile Leu Gln Met Lys Ala Leu Asn Val Glu Lys Val 705 710 715 720 Ile Asn Phe Pro Phe Pro Thr Pro Pro Ser Val Glu Ala Leu Leu Ala 725 730 735 Ala Glu Glu Leu Leu Ile Ala Leu Gly Ala Leu Gln Pro Pro Gln Lys 740 745 750 Ala Glu Arg Val Lys Gln Leu Gln Glu Asn Arg Leu Ser Cys Pro Ile 755 760 765 Thr Ala Leu Gly Arg Thr Met Ala Thr Phe Pro Val Ala Pro Arg Tyr 770 775 780 Ala Lys Met Leu Ala Leu Ser Arg Gln His Gly Cys Leu Pro Tyr Ala 785 790 795 800 Ile Thr Ile Val Ala Ser Met Thr Val Arg Glu Leu Phe Glu Glu Leu 805 810 815 Asp Arg Pro Ala Ala Ser Asp Glu Glu Leu Thr Arg Leu Lys Ser Lys 820 825 830 Arg Ala Arg Val Ala Gln Met Lys Arg Thr Trp Ala Gly Gln Gly Ala 835 840 845 Ser Leu Lys Leu Gly Asp Leu Met Val Leu Leu Gly Ala Val Gly Ala 850 855 860 Cys Glu Tyr Ala Ser Cys Thr Pro Gln Phe Cys Glu Ala Asn Gly Leu 865 870 875 880 Arg Tyr Lys Ala Met Met Glu Ile Arg Arg Leu Arg Gly Gln Leu Thr 885 890 895 Thr Ala Val Asn Ala Val Cys Pro Glu Ala Glu Leu Phe Val Asp Pro 900 905 910 Lys Met Gln Pro Pro Thr Glu Ser Gln Val Thr Tyr Leu Arg Gln Ile 915 920 925 Val Thr Ala Gly Leu Gly Asp His Leu Ala Arg Arg Val Gln Ser Glu 930 935 940 Glu Met Leu Glu Asp Lys Trp Arg Asn Ala Tyr Lys Thr Pro Leu Leu 945 950 955 960 Asp Asp Pro Val Phe Ile His Pro Ser Ser Val Leu Phe Lys Glu Leu 965 970 975 Pro Glu Phe Val Val Tyr Gln Glu Ile Val Glu Thr Thr Lys Met Tyr 980 985 990 Met Lys Gly Val Ser Ser Val Glu Val Gln Trp Ile Pro Ala Leu Leu 995 1000 1005 Pro Ser Tyr Cys Gln Phe Asp Lys Pro Leu Glu Glu Pro Ala Pro Thr 1010 1015 1020 Tyr Cys Pro Glu Arg Gly Arg Val Leu Cys His Arg Ala Ser Val Phe 1025 1030 1035 1040 Tyr Arg Val Gly Trp Pro Leu Pro Ala Ile Glu Val Asp Phe Pro Glu 1045 1050 1055 Gly Ile Asp Arg Tyr Lys His Phe Ala Arg Phe Leu Leu Glu Gly Gln 1060 1065 1070 Val Phe Arg Lys Leu Ala Ser Tyr Arg Ser Cys Leu Leu Ser Ser Pro 1075 1080 1085 Gly Thr Met Leu Lys Thr Trp Ala Arg Leu Gln Pro Arg Thr Glu Ser 1090 1095 1100 Leu Leu Arg Ala Leu Val Ala Glu Lys Ala Asp Cys His Glu Ala Leu 1105 1110 1115 1120 Leu Ala Ala Trp Lys Lys Asn Pro Lys Tyr Leu Leu Ala Glu Tyr Cys 1125 1130 1135 Glu Trp Leu Pro Gln Ala Met His Pro Asp Ile Glu Lys Ala Trp Pro 1140 1145 1150 Pro Thr Thr Val His 1155 <210> 13 <211> 870 <212> PRT <213> Homo sapiens <400> 13 Met Thr Ala Asp Lys Glu Lys Lys Arg Ser Ser Ser Glu Arg Arg Lys 1 5 10 15 Glu Lys Ser Arg Asp Ala Ala Arg Cys Arg Arg Ser Lys Glu Thr Glu 20 25 30 Val Phe Tyr Glu Leu Ala His Glu Leu Pro Leu Pro His Ser Val Ser 35 40 45 Ser His Leu Asp Lys Ala Ser Ile Met Arg Leu Ala Ile Ser Phe Leu 50 55 60 Arg Thr His Lys Leu Leu Ser Ser Val Cys Ser Glu Asn Glu Ser Glu 65 70 75 80 Ala Glu Ala Asp Gln Gln Met Asp Asn Leu Tyr Leu Lys Ala Leu Glu 85 90 95 Gly Phe Ile Ala Val Val Thr Gln Asp Gly Asp Met Ile Phe Leu Ser 100 105 110 Glu Asn Ile Ser Lys Phe Met Gly Leu Thr Gln Val Glu Leu Thr Gly 115 120 125 His Ser Ile Phe Asp Phe Thr His Pro Cys Asp His Glu Glu Ile Arg 130 135 140 Glu Asn Leu Ser Leu Lys Asn Gly Ser Gly Phe Gly Lys Lys Ser Lys 145 150 155 160 Asp Met Ser Thr Glu Arg Asp Phe Phe Met Arg Met Lys Cys Thr Val 165 170 175 Thr Asn Arg Gly Arg Thr Val Asn Leu Lys Ser Ala Thr Trp Lys Val 180 185 190 Leu His Cys Thr Gly Gln Val Lys Val Tyr Asn Asn Cys Pro Pro His 195 200 205 Asn Ser Leu Cys Gly Tyr Lys Glu Pro Leu Leu Ser Cys Leu Ile Ile 210 215 220 Met Cys Glu Pro Ile Gln His Pro Ser His Met Asp Ile Pro Leu Asp 225 230 235 240 Ser Lys Thr Phe Leu Ser Arg His Ser Met Asp Met Lys Phe Thr Tyr 245 250 255 Cys Asp Asp Arg Ile Thr Glu Leu Ile Gly Tyr His Pro Glu Glu Leu 260 265 270 Leu Gly Arg Ser Ala Tyr Glu Phe Tyr His Ala Leu Asp Ser Glu Asn 275 280 285 Met Thr Lys Ser His Gln Asn Leu Cys Thr Lys Gly Gln Val Val Ser 290 295 300 Gly Gly Tyr Arg Met Leu Ala Lys His Gly Gly Tyr Val Trp Leu Glu 305 310 315 320 Thr Gln Gly Thr Val Ile Tyr Asn Pro Arg Asn Leu Gln Pro Gln Cys 325 330 335 Ile Met Cys Val Asn Tyr Val Leu Ser Glu Ile Glu Lys Asn Asp Val 340 345 350 Val Phe Ser Met Asp Gln Thr Glu Ser Leu Phe Lys Pro His Leu Met 355 360 365 Ala Met Asn Ser Ile Phe Asp Ser Ser Gly Lys Gly Ala Val Ser Glu 370 375 380 Lys Ser Asn Phe Leu Phe Thr Lys Leu Lys Glu Glu Pro Glu Glu Leu 385 390 395 400 Ala Gln Leu Ala Pro Thr Pro Gly Asp Ala Ile Ile Ser Leu Asp Phe 405 410 415 Gly Asn Gln Asn Phe Glu Glu Ser Ser Ala Tyr Gly Lys Ala Ile Leu 420 425 430 Pro Pro Ser Gln Pro Trp Ala Thr Glu Leu Arg Ser His Ser Thr Gln 435 440 445 Ser Glu Ala Gly Ser Leu Pro Ala Phe Thr Val Pro Gln Ala Ala Ala 450 455 460 Pro Gly Ser Thr Thr Pro Ser Ala Thr Ser Ser Ser Ser Ser Ser Cys Ser 465 470 475 480 Thr Pro Asn Ser Pro Glu Asp Tyr Tyr Thr Ser Leu Asp Asn Asp Leu 485 490 495 Lys Ile Glu Val Ile Glu Lys Leu Phe Ala Met Asp Thr Glu Ala Lys 500 505 510 Asp Gln Cys Ser Thr Gln Thr Asp Phe Asn Glu Leu Asp Leu Glu Thr 515 520 525 Leu Ala Pro Tyr Ile Pro Met Asp Gly Glu Asp Phe Gln Leu Ser Pro 530 535 540 Ile Cys Pro Glu Glu Arg Leu Leu Ala Glu Asn Pro Gln Ser Thr Pro 545 550 555 560 Gln His Cys Phe Ser Ala Met Thr Asn Ile Phe Gln Pro Leu Ala Pro 565 570 575 Val Ala Pro His Ser Pro Phe Leu Leu Asp Lys Phe Gln Gln Gln Leu 580 585 590 Glu Ser Lys Lys Thr Glu Pro Glu His Arg Pro Met Ser Ser Ile Phe 595 600 605 Phe Asp Ala Gly Ser Lys Ala Ser Leu Pro Pro Cys Cys Gly Gln Ala 610 615 620 Ser Thr Pro Leu Ser Ser Met Gly Gly Arg Ser Asn Thr Gln Trp Pro 625 630 635 640 Pro Asp Pro Leu His Phe Gly Pro Thr Lys Trp Ala Val Gly Asp 645 650 655 Gln Arg Thr Glu Phe Leu Gly Ala Ala Pro Leu Gly Pro Pro Val Ser 660 665 670 Pro Pro His Val Ser Thr Phe Lys Thr Arg Ser Ala Lys Gly Phe Gly 675 680 685 Ala Arg Gly Pro Asp Val Leu Ser Pro Ala Met Val Ala Leu Ser Asn 690 695 700 Lys Leu Lys Leu Lys Arg Gln Leu Glu Tyr Glu Glu Gln Ala Phe Gln 705 710 715 720 Asp Leu Ser Gly Gly Asp Pro Pro Gly Gly Ser Thr Ser His Leu Met 725 730 735 Trp Lys Arg Met Lys Asn Leu Arg Gly Gly Ser Cys Pro Leu Met Pro 740 745 750 Asp Lys Pro Leu Ser Ala Asn Val Pro Asn Asp Lys Phe Thr Gln Asn 755 760 765 Pro Met Arg Gly Leu Gly His Pro Leu Arg His Leu Pro Leu Pro Gln 770 775 780 Pro Pro Ser Ala Ile Ser Pro Gly Glu Asn Ser Lys Ser Arg Phe Pro 785 790 795 800 Pro Gln Cys Tyr Ala Thr Gln Tyr Gln Asp Tyr Ser Leu Ser Ser Ala 805 810 815 His Lys Val Ser Gly Met Ala Ser Arg Leu Leu Gly Pro Ser Phe Glu 820 825 830 Ser Tyr Leu Leu Pro Glu Leu Thr Arg Tyr Asp Cys Glu Val Asn Val 835 840 845 Pro Val Leu Gly Ser Ser Thr Leu Leu Gln Gly Gly Asp Leu Leu Arg 850 855 860 Ala Leu Asp Gln Ala Thr 865 870 <210> 14 <211> 2912 <212> PRT <213> Homo sapiens <400> 14 Met Gly Arg Arg Arg Arg Leu Cys Leu Gln Leu Tyr Phe Leu Trp Leu 1 5 10 15 Gly Cys Val Val Leu Trp Ala Gln Gly Thr Ala Gly Gln Pro Gln Pro 20 25 30 Pro Pro Pro Lys Pro Pro Arg Pro Gln Pro Pro Pro Gln Gln Val Arg 35 40 45 Ser Ala Thr Ala Gly Ser Glu Gly Gly Phe Leu Ala Pro Glu Tyr Arg 50 55 60 Glu Glu Gly Ala Ala Val Ala Ser Arg Val Arg Arg Arg Gly Gln Gln 65 70 75 80 Asp Val Leu Arg Gly Pro Asn Val Cys Gly Ser Arg Phe His Ser Tyr 85 90 95 Cys Cys Pro Gly Trp Lys Thr Leu Pro Gly Gly Asn Gln Cys Ile Val 100 105 110 Pro Ile Cys Arg Asn Ser Cys Gly Asp Gly Phe Cys Ser Arg Pro Asn 115 120 125 Met Cys Thr Cys Ser Ser Gly Gly Gln Ile Ser Ser Thr Cys Gly Ser Lys 130 135 140 Ser Ile Gln Gln Cys Ser Val Arg Cys Met Asn Gly Gly Thr Cys Ala 145 150 155 160 Asp Asp His Cys Gln Cys Gln Lys Gly Tyr Ile Gly Thr Tyr Cys Gly 165 170 175 Gln Pro Val Cys Glu Asn Gly Cys Gln Asn Gly Gly Arg Cys Ile Gly 180 185 190 Pro Asn Arg Cys Ala Cys Val Tyr Gly Phe Thr Gly Pro Gln Cys Glu 195 200 205 Arg Asp Tyr Arg Thr Gly Pro Cys Phe Thr Gln Val Asn Asn Gln Met 210 215 220 Cys Gln Gly Gln Leu Thr Gly Ile Val Cys Thr Lys Thr Leu Cys Cys 225 230 235 240 Ala Thr Ile Gly Arg Ala Trp Gly His Pro Cys Glu Met Cys Pro Ala 245 250 255 Gln Pro Gln Pro Cys Arg Arg Gly Phe Ile Pro Asn Ile Arg Thr Gly 260 265 270 Ala Cys Gln Asp Val Asp Glu Cys Gln Ala Ile Pro Gly Ile Cys Gln 275 280 285 Gly Gly Asn Cys Ile Asn Thr Val Gly Ser Phe Glu Cys Arg Cys Pro 290 295 300 Ala Gly His Lys Gln Ser Glu Thr Thr Gln Lys Cys Glu Asp Ile Asp 305 310 315 320 Glu Cys Ser Ile Ile Pro Gly Ile Cys Glu Thr Gly Glu Cys Ser Asn 325 330 335 Thr Val Gly Ser Tyr Phe Cys Val Cys Pro Arg Gly Tyr Val Thr Ser 340 345 350 Thr Asp Gly Ser Arg Cys Ile Asp Gln Arg Thr Gly Met Cys Phe Ser 355 360 365 Gly Leu Val Asn Gly Arg Cys Ala Gln Glu Leu Pro Gly Arg Met Thr 370 375 380 Lys Met Gln Cys Cys Cys Glu Pro Gly Arg Cys Trp Gly Ile Gly Thr 385 390 395 400 Ile Pro Glu Ala Cys Pro Val Arg Gly Ser Glu Glu Tyr Arg Arg Leu 405 410 415 Cys Met Asp Gly Leu Pro Met Gly Gly Ile Pro Gly Ser Ala Gly Ser 420 425 430 Arg Pro Gly Gly Thr Gly Gly Asn Gly Phe Ala Pro Ser Gly Asn Gly 435 440 445 Asn Gly Tyr Gly Pro Gly Gly Thr Gly Phe Ile Pro Ile Pro Gly Gly 450 455 460 Asn Gly Phe Ser Pro Gly Val Gly Gly Ala Gly Val Gly Ala Gly Gly 465 470 475 480 Gln Gly Pro Ile Ile Thr Gly Leu Thr Ile Leu Asn Gln Thr Ile Asp 485 490 495 Ile Cys Lys His His Ala Asn Leu Cys Leu Asn Gly Arg Cys Ile Pro 500 505 510 Thr Val Ser Ser Tyr Arg Cys Glu Cys Asn Met Gly Tyr Lys Gln Asp 515 520 525 Ala Asn Gly Asp Cys Ile Asp Val Asp Glu Cys Thr Ser Asn Pro Cys 530 535 540 Thr Asn Gly Asp Cys Val Asn Thr Pro Gly Ser Tyr Tyr Cys Lys Cys 545 550 555 560 His Ala Gly Phe Gln Arg Thr Pro Thr Lys Gln Ala Cys Ile Asp Ile 565 570 575 Asp Glu Cys Ile Gln Asn Gly Val Leu Cys Lys Asn Gly Arg Cys Val 580 585 590 Asn Thr Asp Gly Ser Phe Gln Cys Ile Cys Asn Ala Gly Phe Glu Leu 595 600 605 Thr Thr Asp Gly Lys Asn Cys Val Asp His Asp Glu Cys Thr Thr Thr 610 615 620 Asn Met Cys Leu Asn Gly Met Cys Ile Asn Glu Asp Gly Ser Phe Lys 625 630 635 640 Cys Ile Cys Lys Pro Gly Phe Val Leu Ala Pro Asn Gly Arg Tyr Cys 645 650 655 Thr Asp Val Asp Glu Cys Gln Thr Pro Gly Ile Cys Met Asn Gly His 660 665 670 Cys Ile Asn Ser Glu Gly Ser Phe Arg Cys Asp Cys Pro Pro Gly Leu 675 680 685 Ala Val Gly Met Asp Gly Arg Val Cys Val Asp Thr His Met Arg Ser 690 695 700 Thr Cys Tyr Gly Gly Ile Lys Lys Gly Val Cys Val Arg Pro Phe Pro 705 710 715 720 Gly Ala Val Thr Lys Ser Glu Cys Cys Cys Ala Asn Pro Asp Tyr Gly 725 730 735 Phe Gly Glu Pro Cys Gln Pro Cys Pro Ala Lys Asn Ser Ala Glu Phe 740 745 750 His Gly Leu Cys Ser Ser Gly Val Gly Ile Thr Val Asp Gly Arg Asp 755 760 765 Ile Asn Glu Cys Ala Leu Asp Pro Asp Ile Cys Ala Asn Gly Ile Cys 770 775 780 Glu Asn Leu Arg Gly Ser Tyr Arg Cys Asn Cys Asn Ser Gly Tyr Glu 785 790 795 800 Pro Asp Ala Ser Gly Arg Asn Cys Ile Asp Ile Asp Glu Cys Leu Val 805 810 815 Asn Arg Leu Leu Cys Asp Asn Gly Leu Cys Arg Asn Thr Pro Gly Ser 820 825 830 Tyr Ser Cys Thr Cys Pro Pro Gly Tyr Val Phe Arg Thr Glu Thr Glu 835 840 845 Thr Cys Glu Asp Ile Asn Glu Cys Glu Ser Asn Pro Cys Val Asn Gly 850 855 860 Ala Cys Arg Asn Asn Leu Gly Ser Phe Asn Cys Glu Cys Ser Pro Gly 865 870 875 880 Ser Lys Leu Ser Ser Thr Gly Leu Ile Cys Ile Asp Ser Leu Lys Gly 885 890 895 Thr Cys Trp Leu Asn Ile Gln Asp Ser Arg Cys Glu Val Asn Ile Asn 900 905 910 Gly Ala Thr Leu Lys Ser Glu Cys Cys Ala Thr Leu Gly Ala Ala Trp 915 920 925 Gly Ser Pro Cys Glu Arg Cys Glu Leu Asp Thr Ala Cys Pro Arg Gly 930 935 940 Leu Ala Arg Ile Lys Gly Val Thr Cys Glu Asp Val Asn Glu Cys Glu 945 950 955 960 Val Phe Pro Gly Val Cys Pro Asn Gly Arg Cys Val Asn Ser Lys Gly 965 970 975 Ser Phe His Cys Glu Cys Pro Glu Gly Leu Thr Leu Asp Gly Thr Gly 980 985 990 Arg Val Cys Leu Asp Ile Arg Met Glu Gln Cys Tyr Leu Lys Trp Asp 995 1000 1005 Glu Asp Glu Cys Ile His Pro Val Pro Gly Lys Phe Arg Met Asp Ala 1010 1015 1020 Cys Cys Cys Ala Val Gly Ala Ala Trp Gly Thr Glu Cys Glu Glu Cys 1025 1030 1035 1040 Pro Lys Pro Gly Thr Lys Glu Tyr Glu Thr Leu Cys Pro Arg Gly Ala 1045 1050 1055 Gly Phe Ala Asn Arg Gly Asp Val Leu Thr Gly Arg Pro Phe Tyr Lys 1060 1065 1070 Asp Ile Asn Glu Cys Lys Ala Phe Pro Gly Met Cys Thr Tyr Gly Lys 1075 1080 1085 Cys Arg Asn Thr Ile Gly Ser Phe Lys Cys Arg Cys Asn Ser Gly Phe 1090 1095 1100 Ala Leu Asp Met Glu Glu Arg Asn Cys Thr Asp Ile Asp Glu Cys Arg 1105 1110 1115 1120 Ile Ser Pro Asp Leu Cys Gly Ser Gly Ile Cys Val Asn Thr Pro Gly 1125 1130 1135 Ser Phe Glu Cys Glu Cys Phe Glu Gly Tyr Glu Ser Gly Phe Met Met 1140 1145 1150 Met Lys Asn Cys Met Asp Ile Asp Glu Cys Glu Arg Asn Pro Leu Leu 1155 1160 1165 Cys Arg Gly Gly Thr Cys Val Asn Thr Glu Gly Ser Phe Gln Cys Asp 1170 1175 1180 Cys Pro Leu Gly His Glu Leu Ser Pro Ser Arg Glu Asp Cys Val Asp 1185 1190 1195 1200 Ile Asn Glu Cys Ser Leu Ser Asp Asn Leu Cys Arg Asn Gly Lys Cys 1205 1210 1215 Val Asn Met Ile Gly Thr Tyr Gln Cys Ser Cys Asn Pro Gly Tyr Gln 1220 1225 1230 Ala Thr Pro Asp Arg Gln Gly Cys Thr Asp Ile Asp Glu Cys Met Ile 1235 1240 1245 Met Asn Gly Gly Cys Asp Thr Gln Cys Thr Asn Ser Glu Gly Ser Tyr 1250 1255 1260 Glu Cys Ser Cys Ser Glu Gly Tyr Ala Leu Met Pro Asp Gly Arg Ser 1265 1270 1275 1280 Cys Ala Asp Ile Asp Glu Cys Glu Asn Asn Pro Asp Ile Cys Asp Gly 1285 1290 1295 Gly Gln Cys Thr Asn Ile Pro Gly Glu Tyr Arg Cys Leu Cys Tyr Asp 1300 1305 1310 Gly Phe Met Ala Ser Met Asp Met Lys Thr Cys Ile Asp Val Asn Glu 1315 1320 1325 Cys Asp Leu Asn Ser Asn Ile Cys Met Phe Gly Glu Cys Glu Asn Thr 1330 1335 1340 Lys Gly Ser Phe Ile Cys His Cys Gln Leu Gly Tyr Ser Val Lys Lys 1345 1350 1355 1360 Gly Thr Thr Gly Cys Thr Asp Val Asp Glu Cys Glu Ile Gly Ala His 1365 1370 1375 Asn Cys Asp Met His Ala Ser Cys Leu Asn Ile Pro Gly Ser Phe Lys 1380 1385 1390 Cys Ser Cys Arg Glu Gly Trp Ile Gly Asn Gly Ile Lys Cys Ile Asp 1395 1400 1405 Leu Asp Glu Cys Ser Asn Gly Thr His Gln Cys Ser Ile Asn Ala Gln 1410 1415 1420 Cys Val Asn Thr Pro Gly Ser Tyr Arg Cys Ala Cys Ser Glu Gly Phe 1425 1430 1435 1440 Thr Gly Asp Gly Phe Thr Cys Ser Asp Val Asp Glu Cys Ala Glu Asn 1445 1450 1455 Ile Asn Leu Cys Glu Asn Gly Gln Cys Leu Asn Val Pro Gly Ala Tyr 1460 1465 1470 Arg Cys Glu Cys Glu Met Gly Phe Thr Pro Ala Ser Asp Ser Arg Ser 1475 1480 1485 Cys Gln Asp Ile Asp Glu Cys Ser Phe Gln Asn Ile Cys Val Phe Gly 1490 1495 1500 Thr Cys Asn Asn Leu Pro Gly Met Phe His Cys Ile Cys Asp Asp Gly 1505 1510 1515 1520 Tyr Glu Leu Asp Arg Thr Gly Gly Asn Cys Thr Asp Ile Asp Glu Cys 1525 1530 1535 Ala Asp Pro Ile Asn Cys Val Asn Gly Leu Cys Val Asn Thr Pro Gly 1540 1545 1550 Arg Tyr Glu Cys Asn Cys Pro Pro Asp Phe Gln Leu Asn Pro Thr Gly 1555 1560 1565 Val Gly Cys Val Asp Asn Arg Val Gly Asn Cys Tyr Leu Lys Phe Gly 1570 1575 1580 Pro Arg Gly Asp Gly Ser Leu Ser Cys Asn Thr Glu Ile Gly Val Gly 1585 1590 1595 1600 Val Ser Arg Ser Ser Cys Cys Cys Ser Leu Gly Lys Ala Trp Gly Asn 1605 1610 1615 Pro Cys Glu Thr Cys Pro Pro Val Asn Ser Thr Glu Tyr Tyr Thr Leu 1620 1625 1630 Cys Pro Gly Gly Glu Gly Phe Arg Pro Asn Pro Ile Thr Ile Ile Leu 1635 1640 1645 Glu Asp Ile Asp Glu Cys Gln Glu Leu Pro Gly Leu Cys Gln Gly Gly 1650 1655 1660 Asn Cys Ile Asn Thr Phe Gly Ser Phe Gln Cys Glu Cys Pro Gln Gly 1665 1670 1675 1680 Tyr Tyr Leu Ser Glu Asp Thr Arg Ile Cys Glu Asp Ile Asp Glu Cys 1685 1690 1695 Phe Ala His Pro Gly Val Cys Gly Pro Gly Thr Cys Tyr Asn Thr Leu 1700 1705 1710 Gly Asn Tyr Thr Cys Ile Cys Pro Pro Glu Tyr Met Gln Val Asn Gly 1715 1720 1725 Gly His Asn Cys Met Asp Met Arg Lys Ser Phe Cys Tyr Arg Ser Tyr 1730 1735 1740 Asn Gly Thr Thr Cys Glu Asn Glu Leu Pro Phe Asn Val Thr Lys Arg 1745 1750 1755 1760 Met Cys Cys Cys Thr Tyr Asn Val Gly Lys Ala Trp Asn Lys Pro Cys 1765 1770 1775 Glu Pro Cys Pro Thr Pro Gly Thr Ala Asp Phe Lys Thr Ile Cys Gly 1780 1785 1790 Asn Ile Pro Gly Phe Thr Phe Asp Ile His Thr Gly Lys Ala Val Asp 1795 1800 1805 Ile Asp Glu Cys Lys Glu Ile Pro Gly Ile Cys Ala Asn Gly Val Cys 1810 1815 1820 Ile Asn Gln Ile Gly Ser Phe Arg Cys Glu Cys Pro Thr Gly Phe Ser 1825 1830 1835 1840 Tyr Asn Asp Leu Leu Leu Val Cys Glu Asp Ile Asp Glu Cys Ser Asn 1845 1850 1855 Gly Asp Asn Leu Cys Gln Arg Asn Ala Asp Cys Ile Asn Ser Pro Gly 1860 1865 1870 Ser Tyr Arg Cys Glu Cys Ala Ala Gly Phe Lys Leu Ser Pro Asn Gly 1875 1880 1885 Ala Cys Val Asp Arg Asn Glu Cys Leu Glu Ile Pro Asn Val Cys Ser 1890 1895 1900 His Gly Leu Cys Val Asp Leu Gln Gly Ser Tyr Gln Cys Ile Cys His 1905 1910 1915 1920 Asn Gly Phe Lys Ala Ser Gln Asp Gln Thr Met Cys Met Asp Val Asp 1925 1930 1935 Glu Cys Glu Arg His Pro Cys Gly Asn Gly Thr Cys Lys Asn Thr Val 1940 1945 1950 Gly Ser Tyr Asn Cys Leu Cys Tyr Pro Gly Phe Glu Leu Thr His Asn 1955 1960 1965 Asn Asp Cys Leu Asp Ile Asp Glu Cys Ser Ser Phe Phe Gly Gln Val 1970 1975 1980 Cys Arg Asn Gly Arg Cys Phe Asn Glu Ile Gly Ser Phe Lys Cys Leu 1985 1990 1995 2000 Cys Asn Glu Gly Tyr Glu Leu Thr Pro Asp Gly Lys Asn Cys Ile Asp 2005 2010 2015 Thr Asn Glu Cys Val Ala Leu Pro Gly Ser Cys Ser Pro Gly Thr Cys 2020 2025 2030 Gln Asn Leu Glu Gly Ser Phe Arg Cys Ile Cys Pro Pro Gly Tyr Glu 2035 2040 2045 Val Lys Ser Glu Asn Cys Ile Asp Ile Asn Glu Cys Asp Glu Asp Pro 2050 2055 2060 Asn Ile Cys Leu Phe Gly Ser Cys Thr Asn Thr Pro Gly Gly Phe Gln 2065 2070 2075 2080 Cys Leu Cys Pro Pro Gly Phe Val Leu Ser Asp Asn Gly Arg Arg Cys 2085 2090 2095 Phe Asp Thr Arg Gln Ser Phe Cys Phe Thr Asn Phe Glu Asn Gly Lys 2100 2105 2110 Cys Ser Val Pro Lys Ala Phe Asn Thr Thr Lys Ala Lys Cys Cys Cys 2115 2120 2125 Ser Lys Met Pro Gly Glu Gly Trp Gly Asp Pro Cys Glu Leu Cys Pro 2130 2135 2140 Lys Asp Asp Glu Val Ala Phe Gln Asp Leu Cys Pro Tyr Gly His Gly 2145 2150 2155 2160 Thr Val Pro Ser Leu His Asp Thr Arg Glu Asp Val Asn Glu Cys Leu 2165 2170 2175 Glu Ser Pro Gly Ile Cys Ser Asn Gly Gln Cys Ile Asn Thr Asp Gly 2180 2185 2190 Ser Phe Arg Cys Glu Cys Pro Met Gly Tyr Asn Leu Asp Tyr Thr Gly 2195 2200 2205 Val Arg Cys Val Asp Thr Asp Glu Cys Ser Ile Gly Asn Pro Cys Gly 2210 2215 2220 Asn Gly Thr Cys Thr Asn Val Ile Gly Ser Phe Glu Cys Asn Cys Asn 2225 2230 2235 2240 Glu Gly Phe Glu Pro Gly Pro Met Met Asn Cys Glu Asp Ile Asn Glu 2245 2250 2255 Cys Ala Gln Asn Pro Leu Leu Cys Ala Phe Arg Cys Met Asn Thr Phe 2260 2265 2270 Gly Ser Tyr Glu Cys Thr Cys Pro Ile Gly Tyr Ala Leu Arg Glu Asp 2275 2280 2285 Gln Lys Met Cys Lys Asp Leu Asp Glu Cys Ala Glu Gly Leu His Asp 2290 2295 2300 Cys Glu Ser Arg Gly Met Met Cys Lys Asn Leu Ile Gly Thr Phe Met 2305 2310 2315 2320 Cys Ile Cys Pro Pro Gly Met Ala Arg Arg Pro Asp Gly Glu Gly Cys 2325 2330 2335 Val Asp Glu Asn Glu Cys Arg Thr Lys Pro Gly Ile Cys Glu Asn Gly 2340 2345 2350 Arg Cys Val Asn Ile Ile Gly Ser Tyr Arg Cys Glu Cys Asn Glu Gly 2355 2360 2365 Phe Gln Ser Ser Ser Ser Gly Thr Glu Cys Leu Asp Asn Arg Gln Gly 2370 2375 2380 Leu Cys Phe Ala Glu Val Leu Gln Thr Ile Cys Gln Met Ala Ser Ser 2385 2390 2395 2400 Ser Arg Asn Leu Val Thr Lys Ser Glu Cys Cys Cys Asp Gly Gly Arg 2405 2410 2415 Gly Trp Gly His Gln Cys Glu Leu Cys Pro Leu Pro Gly Thr Ala Gln 2420 2425 2430 Tyr Lys Lys Ile Cys Pro His Gly Pro Gly Tyr Thr Thr Asp Gly Arg 2435 2440 2445 Asp Ile Asp Glu Cys Lys Val Met Pro Asn Leu Cys Thr Asn Gly Gln 2450 2455 2460 Cys Ile Asn Thr Met Gly Ser Phe Arg Cys Phe Cys Lys Val Gly Tyr 2465 2470 2475 2480 Thr Thr Asp Ile Ser Gly Thr Ser Cys Ile Asp Leu Asp Glu Cys Ser 2485 2490 2495 Gln Ser Pro Lys Pro Cys Asn Tyr Ile Cys Lys Asn Thr Glu Gly Ser 2500 2505 2510 Tyr Gln Cys Ser Cys Pro Arg Gly Tyr Val Leu Gln Glu Asp Gly Lys 2515 2520 2525 Thr Cys Lys Asp Leu Asp Glu Cys Gln Thr Lys Gln His Asn Cys Gln 2530 2535 2540 Phe Leu Cys Val Asn Thr Leu Gly Gly Phe Thr Cys Lys Cys Pro Pro 2545 2550 2555 2560 Gly Phe Thr Gln His His Thr Ala Cys Ile Asp Asn Asn Glu Cys Gly 2565 2570 2575 Ser Gln Pro Ser Leu Cys Gly Ala Lys Gly Ile Cys Gln Asn Thr Pro 2580 2585 2590 Gly Ser Phe Ser Cys Glu Cys Gln Arg Gly Phe Ser Leu Asp Ala Thr 2595 2600 2605 Gly Leu Asn Cys Glu Asp Val Asp Glu Cys Asp Gly Asn His Arg Cys 2610 2615 2620 Gln His Gly Cys Gln Asn Ile Leu Gly Gly Tyr Arg Cys Gly Cys Pro 2625 2630 2635 2640 Gln Gly Tyr Ile Gln His Tyr Gln Trp Asn Gln Cys Val Asp Glu Asn 2645 2650 2655 Glu Cys Ser Asn Pro Asn Ala Cys Gly Ser Ala Ser Cys Tyr Asn Thr 2660 2665 2670 Leu Gly Ser Tyr Lys Cys Ala Cys Pro Ser Gly Phe Ser Phe Asp Gln 2675 2680 2685 Phe Ser Ser Ala Cys His Asp Val Asn Glu Cys Ser Ser Ser Lys Asn 2690 2695 2700 Pro Cys Asn Tyr Gly Cys Ser Asn Thr Glu Gly Gly Tyr Leu Cys Gly 2705 2710 2715 2720 Cys Pro Pro Gly Tyr Tyr Arg Val Gly Gln Gly His Cys Val Ser Gly 2725 2730 2735 Met Gly Phe Asn Lys Gly Gln Tyr Leu Ser Leu Asp Thr Glu Val Asp 2740 2745 2750 Glu Glu Asn Ala Leu Ser Pro Glu Ala Cys Tyr Glu Cys Lys Ile Asn 2755 2760 2765 Gly Tyr Ser Lys Lys Asp Ser Arg Gln Lys Arg Ser Ile His Glu Pro 2770 2775 2780 Asp Pro Thr Ala Val Glu Gln Ile Ser Leu Glu Ser Val Asp Met Asp 2785 2790 2795 2800 Ser Pro Val Asn Met Lys Phe Asn Leu Ser His Leu Gly Ser Lys Glu 2805 2810 2815 His Ile Leu Glu Leu Arg Pro Ala Ile Gln Pro Leu Asn Asn His Ile 2820 2825 2830 Arg Tyr Val Ile Ser Gln Gly Asn Asp Asp Ser Val Phe Arg Ile His 2835 2840 2845 Gln Arg Asn Gly Leu Ser Tyr Leu His Thr Ala Lys Lys Lys Leu Met 2850 2855 2860 Pro Gly Thr Tyr Thr Leu Glu Ile Thr Ser Ile Pro Leu Tyr Lys Lys 2865 2870 2875 2880 Lys Glu Leu Lys Lys Leu Glu Glu Ser Asn Glu Asp Asp Tyr Leu Leu 2885 2890 2895 Gly Glu Leu Gly Glu Ala Leu Arg Met Arg Leu Gln Ile Gln Leu Tyr 2900 2905 2910 <210> 15 <211> 1020 <212> PRT <213> Homo sapiens <400> 15 Met Gln Ser Cys Ala Arg Ala Trp Gly Leu Arg Leu Gly Arg Gly Val 1 5 10 15 Gly Gly Gly Arg Arg Leu Ala Gly Gly Ser Gly Pro Cys Trp Ala Pro 20 25 30 Arg Ser Arg Asp Ser Ser Ser Gly Gly Gly Asp Ser Ala Ala Ala Gly 35 40 45 Ala Ser Arg Leu Leu Glu Arg Leu Leu Pro Arg His Asp Asp Phe Ala 50 55 60 Arg Arg His Ile Gly Pro Gly Asp Lys Asp Gln Arg Glu Met Leu Gln 65 70 75 80 Thr Leu Gly Leu Ala Ser Ile Asp Glu Leu Ile Glu Lys Thr Val Pro 85 90 95 Ala Asn Ile Arg Leu Lys Arg Pro Leu Lys Met Glu Asp Pro Val Cys 100 105 110 Glu Asn Glu Ile Leu Ala Thr Leu His Ala Ile Ser Ser Lys Asn Gln 115 120 125 Ile Trp Arg Ser Tyr Ile Gly Met Gly Tyr Tyr Asn Cys Ser Val Pro 130 135 140 Gln Thr Ile Leu Arg Asn Leu Leu Glu Asn Ser Gly Trp Ile Thr Gln 145 150 155 160 Tyr Thr Pro Tyr Gln Pro Glu Val Ser Gln Gly Arg Leu Glu Ser Leu 165 170 175 Leu Asn Tyr Gln Thr Met Val Cys Asp Ile Thr Gly Leu Asp Met Ala 180 185 190 Asn Ala Ser Leu Leu Asp Glu Gly Thr Ala Ala Ala Glu Ala Leu Gln 195 200 205 Leu Cys Tyr Arg His Asn Lys Arg Arg Lys Phe Leu Val Asp Pro Arg 210 215 220 Cys His Pro Gln Thr Ile Ala Val Val Gln Thr Arg Ala Lys Tyr Thr 225 230 235 240 Gly Val Leu Thr Glu Leu Lys Leu Pro Cys Glu Met Asp Phe Ser Gly 245 250 255 Lys Asp Val Ser Gly Val Leu Phe Gln Tyr Pro Asp Thr Glu Gly Lys 260 265 270 Val Glu Asp Phe Thr Glu Leu Val Glu Arg Ala His Gln Ser Gly Ser 275 280 285 Leu Ala Cys Cys Ala Thr Asp Leu Leu Ala Leu Cys Ile Leu Arg Pro 290 295 300 Pro Gly Glu Phe Gly Val Asp Ile Ala Leu Gly Ser Ser Gln Arg Phe 305 310 315 320 Gly Val Pro Leu Gly Tyr Gly Gly Pro His Ala Ala Phe Phe Ala Val 325 330 335 Arg Glu Ser Leu Val Arg Met Met Pro Gly Arg Met Val Gly Val Thr 340 345 350 Arg Asp Ala Thr Gly Lys Glu Val Tyr Arg Leu Ala Leu Gln Thr Arg 355 360 365 Glu Gln His Ile Arg Arg Asp Lys Ala Thr Ser Asn Ile Cys Thr Ala 370 375 380 Gln Ala Leu Leu Ala Asn Met Ala Ala Met Phe Ala Ile Tyr His Gly 385 390 395 400 Ser His Gly Leu Glu His Ile Ala Arg Arg Val His Asn Ala Thr Leu 405 410 415 Ile Leu Ser Glu Gly Leu Lys Arg Ala Gly His Gln Leu Gln His Asp 420 425 430 Leu Phe Phe Asp Thr Leu Lys Ile Gln Cys Gly Cys Ser Val Lys Glu 435 440 445 Val Leu Gly Arg Ala Ala Gln Arg Gln Ile Asn Phe Arg Leu Phe Glu 450 455 460 Asp Gly Thr Leu Gly Ile Ser Leu Asp Glu Thr Val Asn Glu Lys Asp 465 470 475 480 Leu Asp Asp Leu Leu Trp Ile Phe Gly Cys Glu Ser Ser Ala Glu Leu 485 490 495 Val Ala Glu Ser Met Gly Glu Glu Cys Arg Gly Ile Pro Gly Ser Val 500 505 510 Phe Lys Arg Thr Ser Pro Phe Leu Thr His Gln Val Phe Asn Ser Tyr 515 520 525 His Ser Glu Thr Asn Ile Val Arg Tyr Met Lys Lys Leu Glu Asn Lys 530 535 540 Asp Ile Ser Leu Val His Ser Met Ile Pro Leu Gly Ser Cys Thr Met 545 550 555 560 Lys Leu Asn Ser Ser Ser Glu Leu Ala Pro Ile Thr Trp Lys Glu Phe 565 570 575 Ala Asn Ile His Pro Phe Val Pro Leu Asp Gln Ala Gln Gly Tyr Gln 580 585 590 Gln Leu Phe Arg Glu Leu Glu Lys Asp Leu Cys Glu Leu Thr Gly Tyr 595 600 605 Asp Gln Val Cys Phe Gln Pro Asn Ser Gly Ala Gln Gly Glu Tyr Ala 610 615 620 Gly Leu Ala Thr Ile Arg Ala Tyr Leu Asn Gln Lys Gly Glu Gly His 625 630 635 640 Arg Thr Val Cys Leu Ile Pro Lys Ser Ala His Gly Thr Asn Pro Ala 645 650 655 Ser Ala His Met Ala Gly Met Lys Ile Gln Pro Val Glu Val Asp Lys 660 665 670 Tyr Gly Asn Ile Asp Ala Val His Leu Lys Ala Met Val Asp Lys His 675 680 685 Lys Glu Asn Leu Ala Ala Ile Met Ile Thr Tyr Pro Ser Thr Asn Gly 690 695 700 Val Phe Glu Glu Asn Ile Ser Asp Val Cys Asp Leu Ile His Gln His 705 710 715 720 Gly Gly Gln Val Tyr Leu Asp Gly Ala Asn Met Asn Ala Gln Val Gly 725 730 735 Ile Cys Arg Pro Gly Asp Phe Gly Ser Asp Val Ser His Leu Asn Leu 740 745 750 His Lys Thr Phe Cys Ile Pro His Gly Gly Gly Gly Pro Gly Met Gly 755 760 765 Pro Ile Gly Val Lys Lys His Leu Ala Pro Phe Leu Pro Asn His Pro 770 775 780 Val Ile Ser Leu Lys Arg Asn Glu Asp Ala Cys Pro Val Gly Thr Val 785 790 795 800 Ser Ala Ala Pro Trp Gly Ser Ser Ser Ile Leu Pro Ile Ser Trp Ala 805 810 815 Tyr Ile Lys Met Met Gly Gly Lys Gly Leu Lys Gln Ala Thr Glu Thr 820 825 830 Ala Ile Leu Asn Ala Asn Tyr Met Ala Lys Arg Leu Glu Thr His Tyr 835 840 845 Arg Ile Leu Phe Arg Gly Ala Arg Gly Tyr Val Gly His Glu Phe Ile 850 855 860 Leu Asp Thr Arg Pro Phe Lys Lys Ser Ala Asn Ile Glu Ala Val Asp 865 870 875 880 Val Ala Lys Arg Leu Gln Asp Tyr Gly Phe His Ala Pro Thr Met Ser 885 890 895 Trp Pro Val Ala Gly Thr Leu Met Val Glu Pro Thr Glu Ser Glu Asp 900 905 910 Lys Ala Glu Leu Asp Arg Phe Cys Asp Ala Met Ile Ser Ile Arg Gln 915 920 925 Glu Ile Ala Asp Ile Glu Glu Gly Arg Ile Asp Pro Arg Val Asn Pro 930 935 940 Leu Lys Met Ser Pro His Ser Leu Thr Cys Val Thr Ser Ser His Trp 945 950 955 960 Asp Arg Pro Tyr Ser Arg Glu Val Ala Ala Phe Pro Leu Pro Phe Val 965 970 975 Lys Pro Glu Asn Lys Phe Trp Pro Thr Ile Ala Arg Ile Asp Asp Ile 980 985 990 Tyr Gly Asp Gln His Leu Val Cys Thr Cys Pro Pro Met Glu Val Tyr 995 1000 1005 Glu Ser Pro Phe Ser Glu Gln Lys Arg Ala Ser Ser 1010 1015 1020 <210> 16 <211> 883 <212> PRT <213> Homo sapiens <400> 16 Met Gln Lys Ile Met His Ile Ser Val Leu Leu Ser Pro Val Leu Trp 1 5 10 15 Gly Leu Ile Phe Gly Val Ser Ser Asn Ser Ile Gln Ile Gly Gly Leu 20 25 30 Phe Pro Arg Gly Ala Asp Gln Glu Tyr Ser Ala Phe Arg Val Gly Met 35 40 45 Val Gln Phe Ser Thr Ser Glu Phe Arg Leu Thr Pro His Ile Asp Asn 50 55 60 Leu Glu Val Ala Asn Ser Phe Ala Val Thr Asn Ala Phe Cys Ser Gln 65 70 75 80 Phe Ser Arg Gly Val Tyr Ala Ile Phe Gly Phe Tyr Asp Lys Lys Ser 85 90 95 Val Asn Thr Ile Thr Ser Phe Cys Gly Thr Leu His Val Ser Phe Ile 100 105 110 Thr Pro Ser Phe Pro Thr Asp Gly Thr His Pro Phe Val Ile Gln Met 115 120 125 Arg Pro Asp Leu Lys Gly Ala Leu Leu Ser Leu Ile Glu Tyr Tyr Gln 130 135 140 Trp Asp Lys Phe Ala Tyr Leu Tyr Asp Ser Asp Arg Gly Leu Ser Thr 145 150 155 160 Leu Gln Ala Val Leu Asp Ser Ala Ala Glu Lys Lys Trp Gln Val Thr 165 170 175 Ala Ile Asn Val Gly Asn Ile Asn Asn Asp Lys Lys Asp Glu Met Tyr 180 185 190 Arg Ser Leu Phe Gln Asp Leu Glu Leu Lys Lys Glu Arg Arg Val Ile 195 200 205 Leu Asp Cys Glu Arg Asp Lys Val Asn Asp Ile Val Asp Gln Val Ile 210 215 220 Thr Ile Gly Lys His Val Lys Gly Tyr His Tyr Ile Ile Ala Asn Leu 225 230 235 240 Gly Phe Thr Asp Gly Asp Leu Leu Lys Ile Gln Phe Gly Gly Ala Asn 245 250 255 Val Ser Gly Phe Gln Ile Val Asp Tyr Asp Asp Ser Leu Val Ser Lys 260 265 270 Phe Ile Glu Arg Trp Ser Thr Leu Glu Glu Lys Glu Tyr Pro Gly Ala 275 280 285 His Thr Thr Thr Ile Lys Tyr Thr Ser Ala Leu Thr Tyr Asp Ala Val 290 295 300 Gln Val Met Thr Glu Ala Phe Arg Asn Leu Arg Lys Gln Arg Ile Glu 305 310 315 320 Ile Ser Arg Arg Gly Asn Ala Gly Asp Cys Leu Ala Asn Pro Ala Val 325 330 335 Pro Trp Gly Gln Gly Val Glu Ile Glu Arg Ala Leu Lys Gln Val Gln 340 345 350 Val Glu Gly Leu Ser Gly Asn Ile Lys Phe Asp Gln Asn Gly Lys Arg 355 360 365 Ile Asn Tyr Thr Ile Asn Ile Met Glu Leu Lys Thr Asn Gly Pro Arg 370 375 380 Lys Ile Gly Tyr Trp Ser Glu Val Asp Lys Met Val Val Thr Leu Thr 385 390 395 400 Glu Leu Pro Ser Gly Asn Asp Thr Ser Gly Leu Glu Asn Lys Thr Val 405 410 415 Val Val Thr Thr Ile Leu Glu Ser Pro Tyr Val Met Met Lys Lys Asn 420 425 430 His Glu Met Leu Glu Gly Asn Glu Arg Tyr Glu Gly Tyr Cys Val Asp 435 440 445 Leu Ala Ala Glu Ile Ala Lys His Cys Gly Phe Lys Tyr Lys Leu Thr 450 455 460 Ile Val Gly Asp Gly Lys Tyr Gly Ala Arg Asp Ala Asp Thr Lys Ile 465 470 475 480 Trp Asn Gly Met Val Gly Glu Leu Val Tyr Gly Lys Ala Asp Ile Ala 485 490 495 Ile Ala Pro Leu Thr Ile Thr Leu Val Arg Glu Glu Val Ile Asp Phe 500 505 510 Ser Lys Pro Phe Met Ser Leu Gly Ile Ser Ile Met Ile Lys Lys Pro 515 520 525 Gln Lys Ser Lys Pro Gly Val Phe Ser Phe Leu Asp Pro Leu Ala Tyr 530 535 540 Glu Ile Trp Met Cys Ile Val Phe Ala Tyr Ile Gly Val Ser Val Val 545 550 555 560 Leu Phe Leu Val Ser Arg Phe Ser Pro Tyr Glu Trp His Thr Glu Glu 565 570 575 Phe Glu Asp Gly Arg Glu Thr Gln Ser Ser Glu Ser Thr Asn Glu Phe 580 585 590 Gly Ile Phe Asn Ser Leu Trp Phe Ser Leu Gly Ala Phe Met Arg Gln 595 600 605 Gly Cys Asp Ile Ser Pro Arg Ser Leu Ser Gly Arg Ile Val Gly Gly 610 615 620 Val Trp Trp Phe Phe Thr Leu Ile Ile Ile Ser Ser Tyr Thr Ala Asn 625 630 635 640 Leu Ala Ala Phe Leu Thr Val Glu Arg Met Val Ser Pro Ile Glu Ser 645 650 655 Ala Glu Asp Leu Ser Lys Gln Thr Glu Ile Ala Tyr Gly Thr Leu Asp 660 665 670 Ser Gly Ser Thr Lys Glu Phe Phe Arg Arg Ser Lys Ile Ala Val Phe 675 680 685 Asp Lys Met Trp Thr Tyr Met Arg Ser Ala Glu Pro Ser Val Phe Val 690 695 700 Arg Thr Thr Ala Glu Gly Val Ala Arg Val Arg Lys Ser Lys Gly Lys 705 710 715 720 Tyr Ala Tyr Leu Leu Glu Ser Thr Met Asn Glu Tyr Ile Glu Gln Arg 725 730 735 Lys Pro Cys Asp Thr Met Lys Val Gly Gly Asn Leu Asp Ser Lys Gly 740 745 750 Tyr Gly Ile Ala Thr Pro Lys Gly Ser Ser Leu Arg Asn Ala Val Asn 755 760 765 Leu Ala Val Leu Lys Leu Asn Glu Gln Gly Leu Leu Asp Lys Leu Lys 770 775 780 Asn Lys Trp Trp Tyr Asp Lys Gly Glu Cys Gly Ser Gly Gly Gly Asp 785 790 795 800 Ser Lys Glu Lys Thr Ser Ala Leu Ser Leu Ser Asn Val Ala Gly Val 805 810 815 Phe Tyr Ile Leu Val Gly Gly Leu Gly Leu Ala Met Leu Val Ala Leu 820 825 830 Ile Glu Phe Cys Tyr Lys Ser Arg Ala Glu Ala Lys Arg Met Lys Val 835 840 845 Ala Lys Asn Ala Gln Asn Ile Asn Pro Ser Ser Ser Gln Asn Ser Gln 850 855 860 Asn Phe Ala Thr Tyr Lys Glu Gly Tyr Asn Val Tyr Gly Ile Glu Ser 865 870 875 880 Val Lys Ile <210> 17 <211> 732 <212> PRT <213> Homo sapiens <400> 17 Met Ser Arg Arg Lys Ile Ser Ser Glu Ser Phe Ser Ser Leu Gly Ser 1 5 10 15 Asp Tyr Leu Glu Thr Ser Pro Glu Glu Glu Gly Glu Cys Pro Leu Ser 20 25 30 Arg Leu Cys Trp Asn Gly Ser Arg Ser Pro Pro Gly Pro Leu Glu Pro 35 40 45 Ser Pro Ala Ala Ala Ala Ala Ala Ala Ala Ala Pro Ala Pro Thr Pro Ala 50 55 60 Ala Ser Ala Ala Ala Ala Ala Ala Thr Ala Gly Ala Arg Arg Val Gln 65 70 75 80 Arg Arg Arg Arg Val Asn Leu Asp Ser Leu Gly Glu Ser Ile Ser Arg 85 90 95 Leu Thr Ala Pro Ser Pro Gln Thr Ile Gln Gln Thr Leu Lys Arg Thr 100 105 110 Leu Gln Tyr Tyr Glu His Gln Val Ile Gly Tyr Arg Asp Ala Glu Lys 115 120 125 Asn Phe His Asn Ile Ser Asn Arg Cys Ser Tyr Ala Asp His Ser Asn 130 135 140 Lys Glu Glu Ile Glu Asp Val Ser Gly Ile Leu Gln Cys Thr Ala Asn 145 150 155 160 Ile Leu Gly Leu Lys Phe Glu Glu Ile Gln Lys Arg Phe Gly Glu Glu 165 170 175 Phe Phe Asn Ile Cys Phe His Glu Asn Glu Arg Val Leu Arg Ala Val 180 185 190 Gly Gly Thr Leu Gln Asp Phe Phe Asn Gly Phe Asp Ala Leu Leu Glu 195 200 205 His Ile Arg Thr Ser Phe Gly Lys Gln Ala Thr Leu Glu Ser Pro Ser 210 215 220 Phe Leu Cys Lys Glu Leu Pro Glu Gly Thr Leu Met Leu His Tyr Phe 225 230 235 240 His Pro His His Ile Val Gly Phe Ala Met Leu Gly Met Ile Lys Ala 245 250 255 Ala Gly Lys Lys Ile Tyr Arg Leu Asp Val Glu Val Glu Gln Val Ala 260 265 270 Asn Glu Lys Leu Cys Ser Asp Val Ser Asn Pro Gly Asn Cys Ser Cys 275 280 285 Leu Thr Phe Leu Ile Lys Glu Cys Glu Asn Thr Asn Ile Met Lys Asn 290 295 300 Leu Pro Gln Gly Thr Ser Gln Val Pro Ala Asp Leu Arg Ile Ser Ile 305 310 315 320 Asn Thr Phe Cys Arg Ala Phe Pro Phe His Leu Met Phe Asp Pro Ser 325 330 335 Met Ser Val Leu Gln Leu Gly Glu Gly Leu Arg Lys Gln Leu Arg Cys 340 345 350 Asp Thr His Lys Val Leu Lys Phe Glu Asp Cys Phe Glu Ile Val Ser 355 360 365 Pro Lys Val Asn Ala Thr Phe Glu Arg Val Leu Leu Arg Leu Ser Thr 370 375 380 Pro Phe Val Ile Arg Thr Lys Pro Glu Ala Ser Gly Ser Glu Asn Lys 385 390 395 400 Asp Lys Val Met Glu Val Lys Gly Gln Met Ile His Val Pro Glu Ser 405 410 415 Asn Ser Ile Leu Phe Leu Gly Ser Pro Cys Val Asp Lys Leu Asp Glu 420 425 430 Leu Met Gly Arg Gly Leu His Leu Ser Asp Ile Pro Ile His Asp Ala 435 440 445 Thr Arg Asp Val Ile Leu Val Gly Glu Gln Ala Lys Ala Gln Asp Gly 450 455 460 Leu Lys Lys Arg Met Asp Lys Leu Lys Ala Thr Leu Glu Arg Thr His 465 470 475 480 Gln Ala Leu Glu Glu Glu Lys Lys Lys Thr Val Asp Leu Leu Tyr Ser 485 490 495 Ile Phe Pro Gly Asp Val Ala Gln Gln Leu Trp Gln Gly Gln Gln Val 500 505 510 Gln Ala Arg Lys Phe Asp Asp Val Thr Met Leu Phe Ser Asp Ile Val 515 520 525 Gly Phe Thr Ala Ile Cys Ala Gln Cys Thr Pro Met Gln Val Ile Ser 530 535 540 Met Leu Asn Glu Leu Tyr Thr Arg Phe Asp His Gln Cys Gly Phe Leu 545 550 555 560 Asp Ile Tyr Lys Val Glu Thr Ile Gly Asp Ala Tyr Cys Val Ala Ala 565 570 575 Gly Leu His Arg Lys Ser Leu Cys His Ala Lys Pro Ile Ala Leu Met 580 585 590 Ala Leu Lys Met Met Glu Leu Ser Glu Glu Val Leu Thr Pro Asp Gly 595 600 605 Arg Pro Ile Gln Met Arg Ile Gly Ile His Ser Gly Ser Val Leu Ala 610 615 620 Gly Val Val Gly Val Arg Met Pro Arg Tyr Cys Leu Phe Gly Asn Asn 625 630 635 640 Val Thr Leu Ala Ser Lys Phe Glu Ser Gly Ser His Pro Arg Arg Ile 645 650 655 Asn Val Ser Pro Thr Thr Tyr Gln Leu Leu Lys Arg Glu Glu Ser Phe 660 665 670 Thr Phe Ile Pro Arg Ser Arg Glu Glu Leu Pro Asp Asn Phe Pro Lys 675 680 685 Glu Ile Pro Gly Ile Cys Tyr Phe Leu Glu Val Arg Thr Gly Pro Lys 690 695 700 Pro Pro Lys Pro Ser Leu Ser Ser Ser Arg Ile Lys Lys Val Ser Tyr 705 710 715 720 Asn Ile Gly Thr Met Phe Leu Arg Glu Thr Ser Leu 725 730 <210> 18 <211> 1051 <212> PRT <213> Homo sapiens <400> 18 Met Gly Pro Gly Pro Ser Arg Ala Pro Arg Ala Pro Arg Leu Met Leu 1 5 10 15 Cys Ala Leu Ala Leu Met Val Ala Ala Gly Gly Cys Val Val Ser Ala 20 25 30 Phe Asn Leu Asp Thr Arg Phe Leu Val Val Lys Glu Ala Gly Asn Pro 35 40 45 Gly Ser Leu Phe Gly Tyr Ser Val Ala Leu His Arg Gln Thr Glu Arg 50 55 60 Gln Gln Arg Tyr Leu Leu Leu Ala Gly Ala Pro Arg Glu Leu Ala Val 65 70 75 80 Pro Asp Gly Tyr Thr Asn Arg Thr Gly Ala Val Tyr Leu Cys Pro Leu 85 90 95 Thr Ala His Lys Asp Asp Cys Glu Arg Met Asn Ile Thr Val Lys Asn 100 105 110 Asp Pro Gly His His Ile Ile Glu Asp Met Trp Leu Gly Val Thr Val 115 120 125 Ala Ser Gln Gly Pro Ala Gly Arg Val Leu Val Cys Ala His Arg Tyr 130 135 140 Thr Gln Val Leu Trp Ser Gly Ser Glu Asp Gln Arg Arg Met Val Gly 145 150 155 160 Lys Cys Tyr Val Arg Gly Asn Asp Leu Glu Leu Asp Ser Ser Asp Asp 165 170 175 Trp Gln Thr Tyr His Asn Glu Met Cys Asn Ser Asn Thr Asp Tyr Leu 180 185 190 Glu Thr Gly Met Cys Gln Leu Gly Thr Ser Gly Gly Phe Thr Gln Asn 195 200 205 Thr Val Tyr Phe Gly Ala Pro Gly Ala Tyr Asn Trp Lys Gly Asn Ser 210 215 220 Tyr Met Ile Gln Arg Lys Glu Trp Asp Leu Ser Glu Tyr Ser Tyr Lys 225 230 235 240 Asp Pro Glu Asp Gln Gly Asn Leu Tyr Ile Gly Tyr Thr Met Gln Val 245 250 255 Gly Ser Phe Ile Leu His Pro Lys Asn Ile Thr Ile Val Thr Gly Ala 260 265 270 Pro Arg His Arg His Met Gly Ala Val Phe Leu Leu Ser Gln Glu Ala 275 280 285 Gly Gly Asp Leu Arg Arg Arg Gln Val Leu Glu Gly Ser Gln Val Gly 290 295 300 Ala Tyr Phe Gly Ser Ala Ile Ala Leu Ala Asp Leu Asn Asn Asp Gly 305 310 315 320 Trp Gln Asp Leu Leu Val Gly Ala Pro Tyr Tyr Phe Glu Arg Lys Glu 325 330 335 Glu Val Gly Gly Ala Ile Tyr Val Phe Met Asn Gln Ala Gly Thr Ser 340 345 350 Phe Pro Ala His Pro Ser Leu Leu Leu His Gly Pro Ser Gly Ser Ala 355 360 365 Phe Gly Leu Ser Val Ala Ser Ile Gly Asp Ile Asn Gln Asp Gly Phe 370 375 380 Gln Asp Ile Ala Val Gly Ala Pro Phe Glu Gly Leu Gly Lys Val Tyr 385 390 395 400 Ile Tyr His Ser Ser Ser Lys Gly Leu Leu Arg Gln Pro Gln Gln Val 405 410 415 Ile His Gly Glu Lys Leu Gly Leu Pro Gly Leu Ala Thr Phe Gly Tyr 420 425 430 Ser Leu Ser Gly Gln Met Asp Val Asp Glu Asn Phe Tyr Pro Asp Leu 435 440 445 Leu Val Gly Ser Leu Ser Asp His Ile Val Leu Leu Arg Ala Arg Pro 450 455 460 Val Ile Asn Ile Val His Lys Thr Leu Val Pro Arg Pro Ala Val Leu 465 470 475 480 Asp Pro Ala Leu Cys Thr Ala Thr Ser Cys Val Gln Val Glu Leu Cys 485 490 495 Phe Ala Tyr Asn Gln Ser Ala Gly Asn Pro Asn Tyr Arg Arg Asn Ile 500 505 510 Thr Leu Ala Tyr Thr Leu Glu Ala Asp Arg Asp Arg Arg Pro Pro Arg 515 520 525 Leu Arg Phe Ala Gly Ser Glu Ser Ala Val Phe His Gly Phe Phe Ser 530 535 540 Met Pro Glu Met Arg Cys Gln Lys Leu Glu Leu Leu Leu Leu Met Asp Asn 545 550 555 560 Leu Arg Asp Lys Leu Arg Pro Ile Ile Ile Ser Met Asn Tyr Ser Leu 565 570 575 Pro Leu Arg Met Pro Asp Arg Pro Arg Leu Gly Leu Arg Ser Leu Asp 580 585 590 Ala Tyr Pro Ile Leu Asn Gln Ala Gln Ala Leu Glu Asn His Thr Glu 595 600 605 Val Gln Phe Gln Lys Glu Cys Gly Pro Asp Asn Lys Cys Glu Ser Asn 610 615 620 Leu Gln Met Arg Ala Ala Phe Val Ser Glu Gln Gln Gln Lys Leu Ser 625 630 635 640 Arg Leu Gln Tyr Ser Arg Asp Val Arg Lys Leu Leu Leu Ser Ile Asn 645 650 655 Val Thr Asn Thr Arg Thr Ser Glu Arg Ser Gly Glu Asp Ala His Glu 660 665 670 Ala Leu Leu Thr Leu Val Val Pro Ala Leu Leu Leu Ser Ser Val 675 680 685 Arg Pro Pro Gly Ala Cys Gln Ala Asn Glu Thr Ile Phe Cys Glu Leu 690 695 700 Gly Asn Pro Phe Lys Arg Asn Gln Arg Met Glu Leu Leu Ile Ala Phe 705 710 715 720 Glu Val Ile Gly Val Thr Leu His Thr Arg Asp Leu Gln Val Gln Leu 725 730 735 Gln Leu Ser Thr Ser Ser His Gln Asp Asn Leu Trp Pro Met Ile Leu 740 745 750 Thr Leu Leu Val Asp Tyr Thr Leu Gln Thr Ser Leu Ser Met Val Asn 755 760 765 His Arg Leu Gln Ser Phe Phe Gly Gly Thr Val Met Gly Glu Ser Gly 770 775 780 Met Lys Thr Val Glu Asp Val Gly Ser Pro Leu Lys Tyr Glu Phe Gln 785 790 795 800 Val Gly Pro Met Gly Glu Gly Leu Val Gly Leu Gly Thr Leu Val Leu 805 810 815 Gly Leu Glu Trp Pro Tyr Glu Val Ser Asn Gly Lys Trp Leu Leu Tyr 820 825 830 Pro Thr Glu Ile Thr Val His Gly Asn Gly Ser Trp Pro Cys Arg Pro 835 840 845 Pro Gly Asp Leu Ile Asn Pro Leu Asn Leu Thr Leu Ser Asp Pro Gly 850 855 860 Asp Arg Pro Ser Ser Pro Gln Arg Arg Arg Arg Gln Leu Asp Pro Gly 865 870 875 880 Gly Gly Gln Gly Pro Pro Pro Val Thr Leu Ala Ala Ala Lys Lys Ala 885 890 895 Lys Ser Glu Thr Val Leu Thr Cys Ala Thr Gly Arg Ala His Cys Val 900 905 910 Trp Leu Glu Cys Pro Ile Pro Asp Ala Pro Val Val Thr Asn Val Thr 915 920 925 Val Lys Ala Arg Val Trp Asn Ser Thr Phe Ile Glu Asp Tyr Arg Asp 930 935 940 Phe Asp Arg Val Arg Val Asn Gly Trp Ala Thr Leu Phe Leu Arg Thr 945 950 955 960 Ser Ile Pro Thr Ile Asn Met Glu Asn Lys Thr Thr Trp Phe Ser Val 965 970 975 Asp Ile Asp Ser Glu Leu Val Glu Glu Leu Pro Ala Glu Ile Glu Leu 980 985 990 Trp Leu Val Leu Val Ala Val Gly Ala Gly Leu Leu Leu Leu Gly Leu 995 1000 1005 Ile Ile Leu Leu Leu Trp Lys Cys Gly Phe Phe Lys Arg Ala Arg Thr 1010 1015 1020 Arg Ala Leu Tyr Glu Ala Lys Arg Gln Lys Ala Glu Met Lys Ser Gln 1025 1030 1035 1040 Pro Ser Glu Thr Glu Arg Leu Thr Asp Asp Tyr 1045 1050 <210> 19 <211> 1032 <212> PRT <213> Homo sapiens <400> 19 Met Ala Trp Glu Ala Arg Arg Glu Pro Gly Pro Arg Arg Ala Ala Val 119 123 128 133 Arg Glu Thr Val Met Leu Leu Leu Cys Leu Gly Val Pro Thr Gly Arg 138 143 148 Pro Tyr Asn Val Asp Thr Glu Ser Ala Leu Leu Tyr Gln Gly Pro His 153 158 163 Asn Thr Leu Phe Gly Tyr Ser Val Val Leu His Ser His Gly Ala Asn 168 173 178 Arg Trp Leu Leu Val Gly Ala Pro Thr Ala Asn Trp Leu Ala Asn Ala 183 188 193 198 Ser Val Ile Asn Pro Gly Ala Ile Tyr Arg Cys Arg Ile Gly Lys Asn 203 208 213 Pro Gly Gln Thr Cys Glu Gln Leu Gln Leu Gly Ser Pro Asn Gly Glu 218 223 228 Pro Cys Gly Lys Thr Cys Leu Glu Glu Arg Asp Asn Gln Trp Leu Gly 233 238 243 Val Thr Leu Ser Arg Gln Pro Gly Glu Asn Gly Ser Ile Val Thr Cys 248 253 258 Gly His Arg Trp Lys Asn Ile Phe Tyr Ile Lys Asn Glu Asn Lys Leu 263 268 273 278 Pro Thr Gly Gly Cys Tyr Gly Val Pro Pro Asp Leu Arg Thr Glu Leu 283 288 293 Ser Lys Arg Ile Ala Pro Cys Tyr Gln Asp Tyr Val Lys Lys Phe Gly 298 303 308 Glu Asn Phe Ala Ser Cys Gln Ala Gly Ile Ser Ser Phe Tyr Thr Lys 313 318 323 Asp Leu Ile Val Met Gly Ala Pro Gly Ser Ser Tyr Trp Thr Gly Ser 328 333 338 Leu Phe Val Tyr Asn Ile Thr Thr Asn Lys Tyr Lys Ala Phe Leu Asp 343 348 353 358 Lys Gln Asn Gln Val Lys Phe Gly Ser Tyr Leu Gly Tyr Ser Val Gly 363 368 373 Ala Gly His Phe Arg Ser Gln His Thr Thr Glu Val Val Gly Gly Ala 378 383 388 Pro Gln His Glu Gln Ile Gly Lys Ala Tyr Ile Phe Ser Ile Asp Glu 393 398 403 Lys Glu Leu Asn Ile Leu His Glu Met Lys Gly Lys Lys Leu Gly Ser 408 413 418 Tyr Phe Gly Ala Ser Val Cys Ala Val Asp Leu Asn Ala Asp Gly Phe 423 428 433 438 Ser Asp Leu Leu Val Gly Ala Pro Met Gln Ser Thr Ile Arg Glu Glu 443 448 453 Gly Arg Val Phe Val Tyr Ile Asn Ser Gly Ser Gly Ala Val Met Asn 458 463 468 Ala Met Glu Thr Asn Leu Val Gly Ser Asp Lys Tyr Ala Ala Arg Phe 473 478 483 Gly Glu Ser Ile Val Asn Leu Gly Asp Ile Asp Asn Asp Gly Phe Glu 488 493 498 Asp Val Ala Ile Gly Ala Pro Gln Glu Asp Asp Leu Gln Gly Ala Ile 503 508 513 518 Tyr Ile Tyr Asn Gly Arg Ala Asp Gly Ile Ser Ser Thr Phe Ser Gln 523 528 533 Arg Ile Glu Gly Leu Gln Ile Ser Lys Ser Leu Ser Met Phe Gly Gln 538 543 548 Ser Ile Ser Gly Gln Ile Asp Ala Asp Asn Asn Gly Tyr Val Asp Val 553 558 563 Ala Val Gly Ala Phe Arg Ser Asp Ser Ala Val Leu Leu Arg Thr Arg 568 573 578 Pro Val Val Ile Val Asp Ala Ser Leu Ser His Pro Glu Ser Val Asn 583 588 593 598 Arg Thr Lys Phe Asp Cys Val Glu Asn Gly Trp Pro Ser Val Cys Ile 603 608 613 Asp Leu Thr Leu Cys Phe Ser Tyr Lys Gly Lys Glu Val Pro Gly Tyr 618 623 628 Ile Val Leu Phe Tyr Asn Met Ser Leu Asp Val Asn Arg Lys Ala Glu 633 638 643 Ser Pro Pro Arg Phe Tyr Phe Ser Ser Asn Gly Thr Ser Asp Val Ile 648 653 658 Thr Gly Ser Ile Gln Val Ser Ser Arg Glu Ala Asn Cys Arg Thr His 663 668 673 678 Gln Ala Phe Met Arg Lys Asp Val Arg Asp Ile Leu Thr Pro Ile Gln 683 688 693 Ile Glu Ala Ala Tyr His Leu Gly Pro His Val Ile Ser Lys Arg Ser 698 703 708 Thr Glu Glu Phe Pro Leu Gln Pro Ile Leu Gln Gln Lys Lys Glu 713 718 723 Lys Asp Ile Met Lys Lys Thr Ile Asn Phe Ala Arg Phe Cys Ala His 728 733 738 Glu Asn Cys Ser Ala Asp Leu Gln Val Ser Ala Lys Ile Gly Phe Leu 743 748 753 758 Lys Pro His Glu Asn Lys Thr Tyr Leu Ala Val Gly Ser Met Lys Thr 763 768 773 Leu Met Leu Asn Val Ser Leu Phe Asn Ala Gly Asp Asp Ala Tyr Glu 778 783 788 Thr Thr Leu His Val Lys Leu Pro Val Gly Leu Tyr Phe Ile Lys Ile 793 798 803 Leu Glu Leu Glu Glu Lys Gln Ile Asn Cys Glu Val Thr Asp Asn Ser 808 813 818 Gly Val Val Gln Leu Asp Cys Ser Ile Gly Tyr Ile Tyr Val Asp His 823 828 833 838 Leu Ser Arg Ile Asp Ile Ser Phe Leu Leu Asp Val Ser Ser Leu Ser 843 848 853 Arg Ala Glu Glu Asp Leu Ser Ile Thr Val His Ala Thr Cys Glu Asn 858 863 868 Glu Glu Glu Met Asp Asn Leu Lys His Ser Arg Val Thr Val Ala Ile 873 878 883 Pro Leu Lys Tyr Glu Val Lys Leu Thr Val His Gly Phe Val Asn Pro 888 893 898 Thr Ser Phe Val Tyr Gly Ser Asn Asp Glu Asn Glu Pro Glu Thr Cys 903 908 913 918 Met Val Glu Lys Met Asn Leu Thr Phe His Val Ile Asn Thr Gly Asn 923 928 933 Ser Met Ala Pro Asn Val Ser Val Glu Ile Met Val Pro Asn Ser Phe 938 943 948 Ser Pro Gln Thr Asp Lys Leu Phe Asn Ile Leu Asp Val Gln Thr Thr 953 958 963 Thr Gly Glu Cys His Phe Glu Asn Tyr Gln Arg Val Cys Ala Leu Glu 968 973 978 Gln Gln Lys Ser Ala Met Gln Thr Leu Lys Gly Ile Val Arg Phe Leu 983 988 993 998 Ser Lys Thr Asp Lys Arg Leu Leu Tyr Cys Ile Lys Ala Asp Pro His 1003 1008 1013 Cys Leu Asn Phe Leu Cys Asn Phe Gly Lys Met Glu Ser Gly Lys Glu 1018 1023 1028 Ala Ser Val His Ile Gln Leu Glu Gly Arg Pro Ser Ile Leu Glu Met 1033 1038 1043 Asp Glu Thr Ser Ala Leu Lys Phe Glu Ile Arg Ala Thr Gly Phe Pro 1048 1053 1058 Glu Pro Asn Pro Arg Val Ile Glu Leu Asn Lys Asp Glu Asn Val Ala 1063 1068 1073 1078 His Val Leu Leu Glu Gly Leu His His Gln Arg Pro Lys Arg Tyr Phe 1083 1088 1093 Thr Ile Val Ile Ile Ser Ser Ser Leu Leu Leu Gly Leu Ile Val Leu 1098 1103 1108 Leu Leu Ile Ser Tyr Val Met Trp Lys Ala Gly Phe Phe Lys Arg Gln 1113 1118 1123 Tyr Lys Ser Ile Leu Gln Glu Glu Asn Arg Arg Asp Ser Trp Ser Tyr 1128 1133 1138 Ile Asn Ser Lys Ser Asn Asp Asp 1143 1148 <210> 20 <211> 998 <212> PRT <213> Homo sapiens <400> 20 Met Lys Asp Ser Gly Asp Ser Lys Asp Gln Gln Leu Met Val Ala Leu 1 5 10 15 Arg Val Arg Pro Ile Ser Val Ala Glu Leu Glu Glu Gly Ala Thr Leu 20 25 30 Ile Ala His Lys Val Asp Glu Gln Met Val Val Leu Met Asp Pro Met 35 40 45 Glu Asp Pro Asp Asp Ile Leu Arg Ala His Arg Ser Arg Glu Lys Ser 50 55 60 Tyr Leu Phe Asp Val Ala Phe Asp Phe Thr Ala Thr Gln Glu Met Val 65 70 75 80 Tyr Gln Ala Thr Thr Lys Ser Leu Ile Glu Gly Val Ile Ser Gly Tyr 85 90 95 Asn Ala Thr Val Phe Ala Tyr Gly Pro Thr Gly Cys Gly Lys Thr Tyr 100 105 110 Thr Met Leu Gly Thr Asp Gln Glu Pro Gly Ile Tyr Val Gln Thr Leu 115 120 125 Asn Asp Leu Phe Arg Ala Ile Glu Glu Thr Ser Asn Asp Met Glu Tyr 130 135 140 Glu Val Ser Met Ser Tyr Leu Glu Ile Tyr Asn Glu Met Ile Arg Asp 145 150 155 160 Leu Leu Asn Pro Ser Leu Gly Tyr Leu Glu Leu Arg Glu Asp Ser Lys 165 170 175 Gly Val Ile Gln Val Ala Gly Ile Thr Glu Val Ser Thr Ile Asn Ala 180 185 190 Lys Glu Ile Met Gln Leu Leu Met Lys Gly Asn Arg Gln Arg Thr Gln 195 200 205 Glu Pro Thr Ala Ala Asn Gln Thr Ser Ser Arg Ser His Ala Val Leu 210 215 220 Gln Val Thr Val Arg Gln Arg Ser Arg Val Lys Asn Ile Leu Gln Glu 225 230 235 240 Val Arg Gln Gly Arg Leu Phe Met Ile Asp Leu Ala Gly Ser Glu Arg 245 250 255 Ala Ser Gln Thr Gln Asn Arg Gly Gln Arg Met Lys Glu Gly Ala His 260 265 270 Ile Asn Arg Ser Leu Leu Ala Leu Gly Asn Cys Ile Asn Ala Leu Ser 275 280 285 Asp Lys Gly Ser Asn Lys Tyr Ile Asn Tyr Arg Asp Ser Lys Leu Thr 290 295 300 Arg Leu Leu Lys Asp Ser Leu Gly Gly Asn Ser Arg Thr Val Met Ile 305 310 315 320 Ala His Ile Ser Pro Ala Ser Ser Ala Phe Glu Glu Ser Arg Asn Thr 325 330 335 Leu Thr Tyr Ala Gly Arg Ala Lys Asn Ile Lys Thr Arg Val Lys Gln 340 345 350 Asn Leu Leu Asn Val Ser Tyr His Ile Ala Gln Tyr Thr Ser Ile Ile 355 360 365 Ala Asp Leu Arg Gly Glu Ile Gln Arg Leu Lys Arg Lys Ile Asp Glu 370 375 380 Gln Thr Gly Arg Gly Gln Ala Arg Gly Arg Gln Asp Arg Gly Asp Ile 385 390 395 400 Arg His Ile Gln Ala Glu Val Gln Leu His Ser Gly Gly Gly Glu Lys 405 410 415 Ala Gly Met Gly Gln Leu Arg Glu Gln Leu Ala Ser Ala Phe Gln Glu 420 425 430 Gln Met Asp Val Arg Arg Arg Leu Leu Glu Leu Glu Asn Arg Ala Met 435 440 445 Glu Val Gln Ile Asp Thr Ser Arg His Leu Leu Thr Ile Ala Gly Trp 450 455 460 Lys His Glu Lys Ser Arg Arg Ala Leu Lys Trp Arg Glu Glu Gln Arg 465 470 475 480 Lys Glu Cys Tyr Ala Lys Asp Asp Ser Glu Lys Asp Ser Asp Thr Gly 485 490 495 Asp Asp Gln Pro Asp Ile Leu Glu Pro Pro Glu Val Ala Ala Ala Arg 500 505 510 Glu Ser Ile Ala Ala Leu Val Asp Glu Gln Lys Gln Leu Arg Lys Gln 515 520 525 Lys Leu Ala Leu Glu Gln Arg Cys Arg Glu Leu Arg Ala Arg Gly Arg 530 535 540 Arg Leu Glu Glu Thr Leu Pro Arg Arg Ile Gly Ser Glu Glu Gln Arg 545 550 555 560 Glu Val Leu Ser Leu Leu Cys Arg Val His Glu Leu Glu Val Glu Asn 565 570 575 Thr Glu Met Gln Ser His Ala Leu Leu Arg Asp Gly Ala Leu Arg His 580 585 590 Arg His Glu Ala Val Arg Arg Leu Glu Gln His Arg Ser Leu Cys Asp 595 600 605 Glu Ile Ile Gln Gly Gln Arg Gln Ile Ile Asp Asp Tyr Asn Leu Ala 610 615 620 Val Pro Gln Arg Leu Glu Glu Leu Tyr Glu Val Tyr Leu Arg Glu Leu 625 630 635 640 Glu Glu Gly Ser Leu Glu Gln Ala Thr Ile Met Asp Gln Val Ala Ser 645 650 655 Arg Ala Leu Gln Asp Ser Ser Leu Pro Lys Ile Thr Pro Ala Gly Thr 660 665 670 Ser Leu Thr Pro Asp Ser Asp Leu Glu Ser Val Lys Thr Leu Ser Ser 675 680 685 Asp Ala Gln His Leu Gln Asn Ser Ala Leu Pro Pro Leu Ser Thr Glu 690 695 700 Ser Glu Gly His His Val Phe Lys Ala Gly Thr Gly Ala Trp Gln Ala 705 710 715 720 Lys Ser Ser Ser Val Pro Thr Pro Pro Pro Ile Gln Leu Gly Ser Leu 725 730 735 Val Thr Gln Glu Ala Pro Ala Gln Asp Ser Leu Gly Ser Trp Ile Asn 740 745 750 Ser Ser Pro Asp Ser Ser Glu Asn Leu Ser Glu Ile Pro Leu Ser His 755 760 765 Lys Glu Arg Lys Glu Ile Leu Thr Gly Thr Lys Cys Ile Trp Val Lys 770 775 780 Ala Ala Arg Arg Arg Ser Arg Ala Leu Gly Thr Glu Gly Arg His Leu 785 790 795 800 Leu Ala Pro Ala Thr Glu Arg Ser Ser Leu Ser Leu His Ser Leu Ser 805 810 815 Glu Gly Asp Asp Ala Arg Pro Pro Gly Pro Leu Ala Cys Lys Arg Pro 820 825 830 Pro Ser Pro Thr Leu Gln His Ala Ala Ser Glu Asp Asn Leu Ser Ser 835 840 845 Ser Thr Gly Glu Ala Pro Ser Arg Ala Val Gly His His Gly Asp Gly 850 855 860 Pro Arg Pro Trp Leu Arg Gly Gln Lys Lys Ser Leu Gly Lys Lys Arg 865 870 875 880 Glu Glu Ser Leu Glu Ala Lys Arg Arg Lys Arg Arg Ser Arg Ser Phe 885 890 895 Glu Val Thr Gly Gin Gly Leu Ser His Pro Lys Thr His Leu Leu Gly 900 905 910 Pro His Gln Ala Glu Arg Ile Ser Asp His Arg Met Pro Val Cys Arg 915 920 925 His Pro Ala Pro Gly Ile Arg His Leu Gly Lys Val Thr Leu Pro Leu 930 935 940 Ala Lys Val Lys Leu Pro Pro Ser Gln Asn Thr Gly Pro Gly Asp Ser 945 950 955 960 Ser Pro Leu Ala Val Pro Pro Asn Pro Gly Gly Gly Ser Arg Arg Ala 965 970 975 Thr Arg Gly Pro Arg Leu Pro His Gly Thr Ser Thr His Gly Lys Asp 980 985 990 Gly Cys Ser Arg His Asn 995 <210> 21 <211> 1816 <212> PRT <213> Homo sapiens <400> 21 Met Ser Gly Ala Ser Val Lys Val Ala Val Arg Val Arg Pro Phe Asn 1 5 10 15 Ser Arg Glu Thr Ser Lys Glu Ser Lys Cys Ile Ile Gln Met Gln Gly 20 25 30 Asn Ser Thr Ser Ile Ile Asn Pro Lys Asn Pro Lys Glu Ala Pro Lys 35 40 45 Ser Phe Ser Phe Asp Tyr Ser Tyr Trp Ser His Thr Ser Pro Glu Asp 50 55 60 Pro Cys Phe Ala Ser Gln Asn Arg Val Tyr Asn Asp Ile Gly Lys Glu 65 70 75 80 Met Leu Leu His Ala Phe Glu Gly Tyr Asn Val Cys Ile Phe Ala Tyr 85 90 95 Gly Gln Thr Gly Ala Gly Lys Ser Tyr Thr Met Met Gly Lys Gln Glu 100 105 110 Glu Ser Gln Ala Gly Ile Ile Pro Gln Leu Cys Glu Glu Leu Phe Glu 115 120 125 Lys Ile Asn Asp Asn Cys Asn Glu Glu Met Ser Tyr Ser Val Glu Val 130 135 140 Ser Tyr Met Glu Ile Tyr Cys Glu Arg Val Arg Asp Leu Leu Asn Pro 145 150 155 160 Lys Asn Lys Gly Asn Leu Arg Val Arg Glu His Pro Leu Leu Gly Pro 165 170 175 Tyr Val Glu Asp Leu Ser Lys Leu Ala Val Thr Ser Tyr Thr Asp Ile 180 185 190 Ala Asp Leu Met Asp Ala Gly Asn Lys Ala Arg Thr Val Ala Ala Thr 195 200 205 Asn Met Asn Glu Thr Ser Ser Arg Ser His Ala Val Phe Thr Ile Val 210 215 220 Phe Thr Gln Lys Lys His Asp Asn Glu Thr Asn Leu Ser Thr Glu Lys 225 230 235 240 Val Ser Lys Ile Ser Leu Val Asp Leu Ala Gly Ser Glu Arg Ala Asp 245 250 255 Ser Thr Gly Ala Lys Gly Thr Arg Leu Lys Glu Gly Ala Asn Ile Asn 260 265 270 Lys Ser Leu Thr Thr Leu Gly Lys Val Ile Ser Ala Leu Ala Glu Val 275 280 285 Asp Asn Cys Thr Ser Lys Ser Lys Lys Lys Lys Lys Thr Asp Phe Ile 290 295 300 Pro Tyr Arg Asp Ser Val Leu Thr Trp Leu Leu Arg Glu Asn Leu Gly 305 310 315 320 Gly Asn Ser Arg Thr Ala Met Val Ala Ala Leu Ser Pro Ala Asp Ile 325 330 335 Asn Tyr Asp Glu Thr Leu Ser Thr Leu Arg Tyr Ala Asp Arg Ala Lys 340 345 350 Gln Ile Lys Cys Asn Ala Val Ile Asn Glu Asp Pro Asn Ala Lys Leu 355 360 365 Val Arg Glu Leu Lys Glu Glu Val Thr Arg Leu Lys Asp Leu Leu Arg 370 375 380 Ala Gln Gly Leu Gly Asp Ile Ile Asp Ile Asp Pro Leu Ile Asp Asp 385 390 395 400 Tyr Ser Gly Ser Gly Ser Lys Tyr Leu Lys Asp Phe Gln Asn Asn Lys 405 410 415 His Arg Tyr Leu Leu Ala Ser Glu Asn Gln Arg Pro Gly His Phe Ser 420 425 430 Thr Ala Ser Met Gly Ser Leu Thr Ser Ser Pro Ser Ser Cys Ser Leu 435 440 445 Ser Ser Gln Val Gly Leu Thr Ser Val Thr Ser Ile Gln Glu Arg Ile 450 455 460 Met Ser Thr Pro Gly Gly Glu Glu Ala Ile Glu Arg Leu Lys Glu Ser 465 470 475 480 Glu Lys Ile Ile Ala Glu Leu Asn Glu Thr Trp Glu Glu Lys Leu Arg 485 490 495 Lys Thr Glu Ala Ile Arg Met Glu Arg Glu Ala Leu Leu Ala Glu Met 500 505 510 Gly Val Ala Ile Arg Glu Asp Gly Gly Thr Leu Gly Val Phe Ser Pro 515 520 525 Lys Lys Thr Pro His Leu Val Asn Leu Asn Glu Asp Pro Leu Met Ser 530 535 540 Glu Cys Leu Leu Tyr Tyr Ile Lys Asp Gly Ile Thr Arg Val Gly Gln 545 550 555 560 Ala Asp Ala Glu Arg Arg Gln Asp Ile Val Leu Ser Gly Ala His Ile 565 570 575 Lys Glu Glu His Cys Ile Phe Arg Ser Glu Arg Ser Asn Ser Gly Glu 580 585 590 Val Ile Val Thr Leu Glu Pro Cys Glu Arg Ser Glu Thr Tyr Val Asn 595 600 605 Gly Lys Arg Val Ser Gln Pro Val Gln Leu Arg Ser Gly Asn Arg Ile 610 615 620 Ile Met Gly Lys Asn His Val Phe Arg Phe Asn His Pro Glu Gln Ala 625 630 635 640 Arg Ala Glu Arg Glu Lys Thr Pro Ser Ala Glu Thr Pro Ser Glu Pro 645 650 655 Val Asp Trp Thr Phe Ala Gln Arg Glu Leu Leu Glu Lys Gln Gly Ile 660 665 670 Asp Met Lys Gln Glu Met Glu Lys Arg Leu Gln Glu Met Glu Ile Leu 675 680 685 Tyr Lys Lys Glu Lys Glu Glu Ala Asp Leu Leu Leu Glu Gln Gln Arg 690 695 700 Leu Asp Tyr Glu Ser Lys Leu Gln Ala Leu Gln Lys Gln Val Glu Thr 705 710 715 720 Arg Ser Leu Ala Ala Glu Thr Thr Glu Glu Glu Glu Glu Glu Glu 725 730 735 Val Pro Trp Thr Gln His Glu Phe Glu Leu Ala Gln Trp Ala Phe Arg 740 745 750 Lys Trp Lys Ser His Gln Phe Thr Ser Leu Arg Asp Leu Leu Trp Gly 755 760 765 Asn Ala Val Tyr Leu Lys Glu Ala Asn Ala Ile Ser Val Glu Leu Lys 770 775 780 Lys Lys Val Gln Phe Gln Phe Val Leu Leu Thr Asp Thr Leu Tyr Ser 785 790 795 800 Pro Leu Pro Pro Glu Leu Leu Pro Thr Glu Met Glu Lys Thr His Glu 805 810 815 Asp Arg Pro Phe Pro Arg Thr Val Val Ala Val Glu Val Gln Asp Leu 820 825 830 Lys Asn Gly Ala Thr His Tyr Trp Ser Leu Glu Lys Leu Lys Gln Arg 835 840 845 Leu Asp Leu Met Arg Glu Met Tyr Asp Arg Ala Gly Glu Met Ala Ser 850 855 860 Ser Ala Gln Asp Glu Ser Glu Thr Thr Val Thr Gly Ser Asp Pro Phe 865 870 875 880 Tyr Asp Arg Phe His Trp Phe Lys Leu Val Gly Ser Ser Pro Ile Phe 885 890 895 His Gly Cys Val Asn Glu Arg Leu Ala Asp Arg Thr Pro Ser Pro Thr 900 905 910 Phe Ser Thr Ala Asp Ser Asp Ile Thr Glu Leu Ala Asp Glu Gln Gln 915 920 925 Asp Glu Met Glu Asp Phe Asp Asp Glu Ala Phe Val Asp Asp Ala Gly 930 935 940 Ser Asp Ala Gly Thr Glu Glu Gly Ser Asp Leu Phe Ser Asp Gly His 945 950 955 960 Asp Pro Phe Tyr Asp Arg Ser Pro Trp Phe Ile Leu Val Gly Arg Ala 965 970 975 Phe Val Tyr Leu Ser Asn Leu Leu Tyr Pro Val Pro Leu Ile His Arg 980 985 990 Val Ala Ile Val Ser Glu Lys Gly Glu Val Arg Gly Phe Leu Arg Val 995 1000 1005 Ala Val Gln Ala Ile Ala Ala Asp Glu Glu Ala Pro Asp Tyr Gly Ser 1010 1015 1020 Gly Ile Arg Gln Ser Gly Thr Ala Lys Ile Ser Phe Asp Asn Glu Tyr 1025 1030 1035 1040 Phe Asn Gln Ser Asp Phe Ser Ser Val Ala Met Thr Arg Ser Gly Leu 1045 1050 1055 Ser Leu Glu Glu Leu Arg Ile Val Glu Gly Gln Gly Gln Ser Ser Glu 1060 1065 1070 Val Ile Thr Pro Pro Glu Glu Ile Ser Arg Ile Asn Asp Leu Asp Leu 1075 1080 1085 Lys Ser Ser Thr Leu Leu Asp Gly Lys Met Val Met Glu Gly Phe Ser 1090 1095 1100 Glu Glu Ile Gly Asn His Leu Lys Leu Gly Ser Ala Phe Thr Phe Arg 1105 1110 1115 1120 Val Thr Val Leu Gln Ala Ser Gly Ile Leu Pro Glu Tyr Ala Asp Ile 1125 1130 1135 Phe Cys Gln Phe Asn Phe Leu His Arg His Asp Glu Ala Phe Ser Thr 1140 1145 1150 Glu Pro Leu Lys Asn Asn Gly Arg Gly Ser Pro Leu Ala Phe Tyr His 1155 1160 1165 Val Gln Asn Ile Ala Val Glu Ile Thr Glu Ser Phe Val Asp Tyr Ile 1170 1175 1180 Lys Thr Lys Pro Ile Val Phe Glu Val Phe Gly His Tyr Gln Gln His 1185 1190 1195 1200 Pro Leu His Leu Gln Gly Gln Glu Leu Asn Ser Pro Pro Gln Pro Cys 1205 1210 1215 Arg Arg Phe Phe Pro Pro Pro Met Pro Leu Ser Lys Pro Val Pro Ala 1220 1225 1230 Thr Lys Leu Asn Thr Met Ser Lys Thr Ser Leu Gly Gln Ser Met Ser 1235 1240 1245 Lys Tyr Asp Leu Leu Val Trp Phe Glu Ile Ser Glu Leu Glu Pro Thr 1250 1255 1260 Gly Glu Tyr Ile Pro Ala Val Val Asp His Thr Ala Gly Leu Pro Cys 1265 1270 1275 1280 Gln Gly Thr Phe Leu Leu His Gln Gly Ile Gln Arg Arg Ile Thr Val 1285 1290 1295 Thr Ile Ile His Glu Lys Gly Ser Glu Leu His Trp Lys Asp Val Arg 1300 1305 1310 Glu Leu Val Val Gly Arg Ile Arg Asn Lys Pro Glu Val Asp Glu Ala 1315 1320 1325 Ala Val Asp Ala Ile Leu Ser Leu Asn Ile Ile Ser Ala Lys Tyr Leu 1330 1335 1340 Lys Ser Ser His Asn Ser Ser Arg Thr Phe Tyr Arg Phe Glu Ala Val 1345 1350 1355 1360 Trp Asp Ser Ser Leu His Asn Ser Leu Leu Leu Asn Arg Val Thr Pro 1365 1370 1375 Tyr Gly Glu Lys Ile Tyr Met Thr Leu Ser Ala Tyr Leu Glu Leu Asp 1380 1385 1390 His Cys Ile Gln Pro Ala Val Ile Thr Lys Asp Val Cys Met Val Phe 1395 1400 1405 Tyr Ser Arg Asp Ala Lys Ile Ser Pro Pro Arg Ser Leu Arg Ser Leu 1410 1415 1420 Phe Gly Ser Gly Tyr Ser Lys Ser Pro Asp Ser Asn Arg Val Thr Gly 1425 1430 1435 1440 Ile Tyr Glu Leu Ser Leu Cys Lys Met Ser Asp Thr Gly Ser Pro Gly 1445 1450 1455 Met Gln Arg Arg Arg Arg Lys Ile Leu Asp Thr Ser Val Ala Tyr Val 1460 1465 1470 Arg Gly Glu Glu Asn Leu Ala Gly Trp Arg Pro Arg Gly Asp Ser Leu 1475 1480 1485 Ile Leu Glu His Gln Trp Glu Leu Glu Lys Leu Glu Leu Leu His Glu 1490 1495 1500 Val Glu Lys Thr Arg His Phe Leu Leu Leu Arg Glu Arg Leu Gly Asp 1505 1510 1515 1520 Ser Ile Pro Lys Ser Leu Ser Asp Ser Leu Ser Pro Ser Leu Ser Ser 1525 1530 1535 Gly Thr Leu Ser Thr Ser Thr Ser Ile Ser Ser Gln Ile Ser Thr Thr 1540 1545 1550 Thr Phe Glu Ser Ala Ile Thr Pro Ser Glu Ser Ser Gly Tyr Asp Ser 1555 1560 1565 Gly Asp Ile Glu Ser Leu Val Asp Arg Glu Lys Glu Leu Ala Thr Lys 1570 1575 1580 Cys Leu Gln Leu Leu Thr His Thr Phe Asn Arg Glu Phe Ser Gln Val 1585 1590 1595 1600 His Gly Ser Val Ser Asp Cys Lys Leu Ser Asp Ile Ser Pro Ile Gly 1605 1610 1615 Arg Asp Pro Ser Glu Ser Ser Phe Ser Ser Ala Thr Leu Thr Pro Ser 1620 1625 1630 Ser Thr Cys Pro Ser Leu Val Asp Ser Arg Ser Asn Ser Leu Asp Gln 1635 1640 1645 Lys Thr Pro Glu Ala Asn Ser Arg Ala Ser Ser Pro Cys Pro Glu Phe 1650 1655 1660 Glu Gln Phe Gln Ile Val Pro Ala Val Glu Thr Pro Tyr Leu Ala Arg 1665 1670 1675 1680 Ala Gly Lys Asn Glu Phe Leu Asn Leu Val Pro Asp Ile Glu Glu Ile 1685 1690 1695 Arg Pro Ser Ser Val Val Ser Lys Lys Gly Tyr Leu His Phe Lys Glu 1700 1705 1710 Pro Leu Tyr Ser Asn Trp Ala Lys His Phe Val Val Val Arg Arg Pro 1715 1720 1725 Tyr Val Phe Ile Tyr Asn Ser Asp Lys Asp Pro Val Glu Arg Gly Ile 1730 1735 1740 Ile Asn Leu Ser Thr Ala Gln Val Glu Tyr Ser Glu Asp Gln Gln Ala 1745 1750 1755 1760 Met Val Lys Thr Pro Asn Thr Phe Ala Val Cys Thr Lys His Arg Gly 1765 1770 1775 Val Leu Leu Gln Ala Leu Asn Asp Lys Asp Met Asn Asp Trp Leu Tyr 1780 1785 1790 Ala Phe Asn Pro Leu Leu Ala Gly Thr Ile Arg Ser Lys Leu Ser Arg 1795 1800 1805 Arg Cys Pro Ser Gln Ser Lys Tyr 1810 1815 <210> 22 <211> 890 <212> PRT <213> Homo sapiens <400> 22 Met Asn Tyr Val Gly Gln Leu Ala Gly Gln Val Phe Val Thr Val Lys 1 5 10 15 Glu Leu Tyr Lys Gly Leu Asn Pro Ala Thr Leu Ser Gly Cys Ile Asp 20 25 30 Ile Ile Val Ile Arg Gln Pro Asn Gly Asn Leu Gln Cys Ser Pro Phe 35 40 45 His Val Arg Phe Gly Lys Met Gly Val Leu Arg Ser Arg Glu Lys Val 50 55 60 Val Asp Ile Glu Ile Asn Gly Glu Ser Val Asp Leu His Met Lys Leu 65 70 75 80 Gly Asp Asn Gly Glu Ala Phe Phe Val Gln Glu Thr Asp Asn Asp Gln 85 90 95 Glu Val Ile Pro Met His Leu Ala Thr Ser Pro Ile Leu Ser Glu Gly 100 105 110 Ala Ser Arg Met Glu Cys Gln Leu Lys Arg Gly Ser Val Asp Arg Met 115 120 125 Arg Gly Leu Asp Pro Ser Thr Pro Ala Gln Val Ile Ala Pro Ser Glu 130 135 140 Thr Pro Ser Ser Ser Ser Val Val Lys Lys Arg Arg Lys Arg Arg Arg 145 150 155 160 Lys Ser Gln Leu Asp Ser Leu Lys Arg Asp Asp Asn Met Asn Thr Ser 165 170 175 Glu Asp Glu Asp Met Phe Pro Ile Glu Met Ser Ser Asp Glu Ala Met 180 185 190 Glu Leu Leu Glu Ser Ser Arg Thr Leu Pro Asn Asp Ile Pro Phe 195 200 205 Gln Asp Asp Ile Pro Glu Glu Asn Leu Ser Leu Ala Val Ile Tyr Pro 210 215 220 Gln Ser Ala Ser Tyr Pro Asn Ser Asp Arg Glu Trp Ser Pro Thr Pro 225 230 235 240 Ser Pro Ser Gly Ser Arg Pro Ser Thr Pro Lys Ser Asp Ser Glu Leu 245 250 255 Val Ser Lys Ser Thr Glu Arg Thr Gly Gln Lys Asn Pro Glu Met Leu 260 265 270 Trp Leu Trp Gly Glu Leu Pro Gln Ala Ala Lys Ser Ser Ser Pro His 275 280 285 Lys Met Lys Glu Ser Ser Pro Leu Ser Ser Arg Lys Ile Cys Asp Lys 290 295 300 Ser His Phe Gln Ala Ile His Ser Glu Ser Ser Asp Thr Phe Ser Asp 305 310 315 320 Gln Ser Pro Thr Leu Val Gly Gly Ala Leu Leu Asp Gln Asn Lys Pro 325 330 335 Gln Thr Glu Met Gln Phe Val Asn Glu Glu Asp Leu Glu Thr Leu Gly 340 345 350 Ala Ala Ala Pro Leu Leu Pro Met Ile Glu Glu Leu Lys Pro Pro Ser 355 360 365 Ala Ser Val Val Gln Thr Ala Asn Lys Thr Asp Ser Pro Ser Arg Lys 370 375 380 Arg Asp Lys Arg Ser Arg His Leu Gly Ala Asp Gly Val Tyr Leu Asp 385 390 395 400 Asp Leu Thr Asp Met Asp Pro Glu Val Ala Ala Leu Tyr Phe Pro Lys 405 410 415 Asn Gly Asp Pro Ser Gly Leu Ala Lys His Ala Ser Asp Asn Gly Ala 420 425 430 Arg Ser Ala Asn Gln Ser Pro Gln Ser Val Gly Ser Ser Gly Val Asp 435 440 445 Ser Gly Val Glu Ser Thr Ser Asp Gly Leu Arg Asp Leu Pro Ser Ile 450 455 460 Ala Ile Ser Leu Cys Gly Gly Leu Ser Asp His Arg Glu Ile Thr Lys 465 470 475 480 Asp Ala Phe Leu Glu Gln Ala Val Ser Tyr Gln Gln Phe Val Asp Asn 485 490 495 Pro Ala Ile Ile Asp Asp Pro Asn Leu Val Val Lys Ile Gly Ser Lys 500 505 510 Tyr Tyr Asn Trp Thr Thr Ala Ala Pro Leu Leu Leu Ala Met Gln Ala 515 520 525 Phe Gln Lys Pro Leu Pro Lys Ala Thr Val Glu Ser Ile Met Arg Asp 530 535 540 Lys Met Pro Lys Lys Gly Gly Arg Trp Trp Phe Ser Trp Arg Gly Arg 545 550 555 560 Asn Thr Thr Ile Lys Glu Glu Ser Lys Pro Glu Gln Cys Leu Ala Gly 565 570 575 Lys Ala His Ser Thr Gly Glu Gln Pro Pro Gln Leu Ser Leu Ala Thr 580 585 590 Arg Val Lys His Glu Ser Ser Ser Ser Asp Glu Glu Arg Ala Ala Ala 595 600 605 Lys Pro Ser Asn Ala Gly His Leu Pro Leu Leu Pro Asn Val Ser Tyr 610 615 620 Lys Lys Thr Leu Arg Leu Thr Ser Glu Gln Leu Lys Ser Leu Lys Leu 625 630 635 640 Lys Asn Gly Pro Asn Asp Val Val Phe Ser Val Thr Thr Gln Tyr Gln 645 650 655 Gly Thr Cys Arg Cys Glu Gly Thr Ile Tyr Leu Trp Asn Trp Asp Asp 660 665 670 Lys Val Ile Ile Ser Asp Ile Asp Gly Thr Ile Thr Arg Ser Asp Thr 675 680 685 Leu Gly His Ile Leu Pro Thr Leu Gly Lys Asp Trp Thr His Gln Gly 690 695 700 Ile Ala Lys Leu Tyr His Lys Val Ser Gln Asn Gly Tyr Lys Phe Leu 705 710 715 720 Tyr Cys Ser Ala Arg Ala Ile Gly Met Ala Asp Met Thr Arg Gly Tyr 725 730 735 Leu His Trp Val Asn Glu Arg Gly Thr Val Leu Pro Gln Gly Pro Leu 740 745 750 Leu Leu Ser Pro Ser Ser Leu Phe Ser Ala Leu His Arg Glu Val Ile 755 760 765 Glu Lys Lys Pro Glu Lys Phe Lys Val Gln Cys Leu Thr Asp Ile Lys 770 775 780 Asn Leu Phe Phe Pro Asn Thr Glu Pro Phe Tyr Ala Ala Phe Gly Asn 785 790 795 800 Arg Pro Ala Asp Val Tyr Ser Tyr Lys Gln Val Gly Val Ser Leu Asn 805 810 815 Arg Ile Phe Thr Val Asn Pro Lys Gly Glu Leu Val Gln Glu His Ala 820 825 830 Lys Thr Asn Ile Ser Ser Tyr Val Arg Leu Cys Glu Val Val Asp His 835 840 845 Val Phe Pro Leu Leu Lys Arg Ser His Ser Ser Asp Phe Pro Cys Ser 850 855 860 Asp Thr Phe Ser Asn Phe Thr Phe Trp Arg Glu Pro Leu Pro Pro Phe 865 870 875 880 Glu Asn Gln Asp Ile His Ser Ala Ser Ala 885 890 <210> 23 <211> 767 <212> PRT <213> Homo sapiens <400> 23 Met Ser His Ala Val Thr Ile Glu Glu Pro Gln Ala Gln Pro Gln Val 1 5 10 15 Ser Gln Thr Arg Tyr Arg Glu Arg Ser Arg Ala Gly Ser His Ile Ser 20 25 30 Ser Asn Arg Ala Tyr Asp Phe Leu Tyr Asp Pro Leu Phe Ile Val Ser 35 40 45 Ser Glu Lys Asp His Thr Gln Ala Asn Ile Gln Ala Thr Leu Ile Arg 50 55 60 Ser Arg Leu Arg Lys Val Pro Arg Phe Lys Thr Met Phe Ser Asn Leu 65 70 75 80 Ile His Tyr Pro Arg Tyr Ser Leu Tyr Trp Ser Lys Ser Asp Pro Val 85 90 95 Pro Pro Phe Ile Ser Arg Glu Trp Lys Gly His Lys Glu Lys His Arg 100 105 110 Glu Ala Leu Arg Gln Leu Thr Thr Thr Asp Ala Ser Phe Gln Met Pro 115 120 125 Lys Glu Val Tyr Glu Asp Pro Glu Val Thr Gly Lys Asn Arg Tyr Lys 130 135 140 Tyr Phe Glu Arg Pro Phe Leu Pro Phe Phe Gln Gln Met Pro Phe Asn 145 150 155 160 Val Val Tyr Ala Val Ser Lys Ala Glu Pro Tyr Thr Phe Pro Pro Thr 165 170 175 Ser Thr Lys His Leu Ser Ile Pro Ser Lys Ser Thr Val Gly Thr Gln 180 185 190 Thr Asp Tyr Arg Asp Ala Asp Val Gln Thr Asp Pro Tyr Ser Ala Glu 195 200 205 Tyr Val Val Cys Gln Asp Ser Ile Pro Glu Leu Leu Thr Leu Ala Thr 210 215 220 Leu Thr Trp Gly Arg Gly Leu Pro Ala Gly Gln Ala Glu Val Glu Met 225 230 235 240 Ile Glu Arg Ala Arg Glu Lys Arg Ala Trp Glu Ala Ser Leu Pro Ala 245 250 255 Leu Ser Asp Thr Ser Gln Phe Glu Lys Arg Arg Lys Met Met Asn Glu 260 265 270 Met Glu Arg Lys Glu Trp Ala Phe Arg Glu Gln Glu Ile Glu Lys Leu 275 280 285 Gln Glu Ile Arg Leu Glu Val Leu Lys Glu Leu Leu Arg Lys Arg Glu 290 295 300 Glu Asn Gln Asn Glu Val Asn Met Lys His Leu Asn Ala Arg Trp Ser 305 310 315 320 Lys Leu Gln Glu Gly Lys Glu Ala Lys Met Ala Lys Ile Gln Arg Thr 325 330 335 His Val Ser Thr Ile Arg Lys Leu Val Gly Lys Arg Lys Asn Ile Glu 340 345 350 Gly Lys Leu Glu Arg Arg Asn Ile Ile Lys Asp Tyr Ser Asp Tyr Ala 355 360 365 Ser Gln Val Tyr Gly Pro Leu Ser Arg Leu Gly Cys Phe Pro Asp Asn 370 375 380 Asn Ser Glu Asp Phe Val Val Lys Asn Tyr Tyr Leu Asn Thr Tyr Glu 385 390 395 400 Gly Leu Val Glu Leu Glu Ser Cys Leu Pro Asp Phe Val Thr Gln Pro 405 410 415 Gln Ile Arg Ala Pro Lys Pro Lys Val Ile Thr Thr Lys Ala Gly Phe 420 425 430 Leu Lys Arg Ala Ala Arg Leu Asp Tyr Glu Leu Ala Glu Val His Lys 435 440 445 Ala Leu Leu Asp Lys Lys Asn Lys Val Leu Glu Val Lys Lys Pro Pro 450 455 460 Arg Phe Leu Gln Arg Asn Pro Ile Pro Gln Pro Arg Leu Pro Thr Pro 465 470 475 480 Thr Leu Glu Met Thr Ser Asn Glu Glu Glu Glu Met Glu Met Ala Val 485 490 495 Ile Tyr Leu Gln Lys Leu Leu Arg Gly Arg Val Val Gln Asn Met Met 500 505 510 Phe Glu Gly Lys Glu Lys Arg Leu Glu Leu Ile Gln Glu Leu Arg Thr 515 520 525 Cys His Ala Leu Gln Glu Asp Glu Lys Leu Val Lys Lys Ala Glu Lys 530 535 540 Gln Val Thr Leu Ala Leu Gln Arg Gln Arg Asn Leu His Glu His Lys 545 550 555 560 Val Ser Leu Val Glu Asn His Leu Ala Gly Leu Glu Gly Arg Ala Leu 565 570 575 Ala Asp Met Phe Asp Phe Leu Ser Lys Glu Leu Val Arg Leu Gln Glu 580 585 590 Glu Arg Arg Ile His Ala Phe Val Met Leu Ala Glu Arg Gln Arg Arg 595 600 605 Val Arg Glu Ala Glu Glu Ser Gly Arg Arg Gln Val Glu Lys Gln Arg 610 615 620 Leu Arg Glu Glu Asp Glu Ile Phe Lys Glu Val Val Lys Val His His 625 630 635 640 Ser Thr Ile Ser Ser Tyr Leu Glu Asp Ile Ile Leu Asn Thr Glu Ala 645 650 655 Asn Thr Ala Glu Glu Gln Ala Arg Ala Glu Ile Glu Lys Met Ala Glu 660 665 670 Lys Ile Asn Asp Ile Ala Tyr Glu Met Glu Ser Arg Arg Thr Tyr Leu 675 680 685 Gln Ser Glu Glu Ile Val Ala Glu Leu Val Tyr Ser Phe Leu Ile Pro 690 695 700 Glu Val Gln Lys Tyr Phe Val Lys Glu Lys Val Arg Asn Ala Gln Arg 705 710 715 720 Lys His Ile Leu Ala Ala His Gln Ile Ile His Ser Tyr Thr Glu Ser 725 730 735 Met Val Gln Lys Lys Leu Thr Glu Gly Glu Gln Asp Glu Ala Ser Asn 740 745 750 Ala Ala Met Leu Leu Glu Lys Glu Thr Gln Asn Glu Asn Asn Ser 755 760 765 <210> 24 <211> 840 <212> PRT <213> Homo sapiens <400> 24 Met Asn Gly Glu Tyr Arg Gly Arg Gly Phe Gly Arg Gly Arg Phe Gln 1 5 10 15 Ser Trp Lys Arg Gly Arg Gly Gly Gly Asn Phe Ser Gly Lys Trp Arg 20 25 30 Glu Arg Glu His Arg Pro Asp Leu Ser Lys Thr Thr Gly Lys Arg Thr 35 40 45 Ser Glu Gln Thr Pro Gln Phe Leu Leu Ser Thr Lys Thr Pro Gln Ser 50 55 60 Met Gln Ser Thr Leu Asp Arg Phe Ile Pro Tyr Lys Gly Trp Lys Leu 65 70 75 80 Tyr Phe Ser Glu Val Tyr Ser Asp Ser Ser Pro Leu Ile Glu Lys Ile 85 90 95 Gln Ala Phe Glu Lys Phe Phe Thr Arg His Ile Asp Leu Tyr Asp Lys 100 105 110 Asp Glu Ile Glu Arg Lys Gly Ser Ile Leu Val Asp Phe Lys Glu Leu 115 120 125 Thr Glu Gly Gly Glu Val Thr Asn Leu Ile Pro Asp Ile Ala Thr Glu 130 135 140 Leu Arg Asp Ala Pro Glu Lys Thr Leu Ala Cys Met Gly Leu Ala Ile 145 150 155 160 His Gln Val Leu Thr Lys Asp Leu Glu Arg His Ala Ala Glu Leu Gln 165 170 175 Ala Gln Glu Gly Leu Ser Asn Asp Gly Glu Thr Met Val Asn Val Pro 180 185 190 His Ile His Ala Arg Val Tyr Asn Tyr Glu Pro Leu Thr Gln Leu Lys 195 200 205 Asn Val Arg Ala Asn Tyr Tyr Gly Lys Tyr Ile Ala Leu Arg Gly Thr 210 215 220 Val Val Arg Val Ser Asn Ile Lys Pro Leu Cys Thr Lys Met Ala Phe 225 230 235 240 Leu Cys Ala Ala Cys Gly Glu Ile Gln Ser Phe Pro Leu Pro Asp Gly 245 250 255 Lys Tyr Ser Leu Pro Thr Lys Cys Pro Val Pro Val Cys Arg Gly Arg 260 265 270 Ser Phe Thr Ala Leu Arg Ser Ser Pro Leu Thr Val Thr Met Asp Trp 275 280 285 Gln Ser Ile Lys Ile Gln Glu Leu Met Ser Asp Asp Gln Arg Glu Ala 290 295 300 Gly Arg Ile Pro Arg Thr Ile Glu Cys Glu Leu Val His Asp Leu Val 305 310 315 320 Asp Ser Cys Val Pro Gly Asp Thr Val Thr Ile Thr Gly Ile Val Lys 325 330 335 Val Ser Asn Ala Glu Glu Gly Ser Arg Asn Lys Asn Asp Lys Cys Met 340 345 350 Phe Leu Leu Tyr Ile Glu Ala Asn Ser Ile Ser Asn Ser Lys Gly Gln 355 360 365 Lys Thr Lys Ser Ser Glu Asp Gly Cys Lys His Gly Met Leu Met Glu 370 375 380 Phe Ser Leu Lys Asp Leu Tyr Ala Ile Gln Glu Ile Gln Ala Glu Glu 385 390 395 400 Asn Leu Phe Lys Leu Ile Val Asn Ser Leu Cys Pro Val Ile Phe Gly 405 410 415 His Glu Leu Val Lys Ala Gly Leu Ala Leu Ala Leu Phe Gly Gly Ser 420 425 430 Gln Lys Tyr Ala Asp Asp Lys Asn Arg Ile Pro Ile Arg Gly Asp Pro 435 440 445 His Ile Leu Val Val Gly Asp Pro Gly Leu Gly Lys Ser Gln Met Leu 450 455 460 Gln Ala Ala Cys Asn Val Ala Pro Arg Gly Val Tyr Val Cys Gly Asn 465 470 475 480 Thr Thr Thr Thr Ser Gly Leu Thr Val Thr Leu Ser Lys Asp Ser Ser 485 490 495 Ser Gly Asp Phe Ala Leu Glu Ala Gly Ala Leu Val Leu Gly Asp Gln 500 505 510 Gly Ile Cys Gly Ile Asp Glu Phe Asp Lys Met Gly Asn Gln His Gln 515 520 525 Ala Leu Leu Glu Ala Met Glu Gln Gln Ser Ile Ser Leu Ala Lys Ala 530 535 540 Gly Val Val Cys Ser Leu Pro Ala Arg Thr Ser Ile Ile Ala Ala Ala 545 550 555 560 Asn Pro Val Gly Gly His Tyr Asn Lys Ala Lys Thr Val Ser Glu Asn 565 570 575 Leu Lys Met Gly Ser Ala Leu Leu Ser Arg Phe Asp Leu Val Phe Ile 580 585 590 Leu Leu Asp Thr Pro Asn Glu His His Asp His Leu Leu Ser Glu His 595 600 605 Val Ile Ala Ile Arg Ala Gly Lys Gln Arg Thr Ile Ser Ser Ala Thr 610 615 620 Val Ala Arg Met Asn Ser Gln Asp Ser Asn Thr Ser Val Leu Glu Val 625 630 635 640 Val Ser Glu Lys Pro Leu Ser Glu Arg Leu Lys Val Val Pro Gly Glu 645 650 655 Thr Ile Asp Pro Ile Pro His Gln Leu Leu Arg Lys Tyr Ile Gly Tyr 660 665 670 Ala Arg Gln Tyr Val Tyr Pro Arg Leu Ser Thr Glu Ala Ala Arg Val 675 680 685 Leu Gln Asp Phe Tyr Leu Glu Leu Arg Lys Gln Ser Gln Arg Leu Asn 690 695 700 Ser Ser Pro Ile Thr Thr Arg Gln Leu Glu Ser Leu Ile Arg Leu Thr 705 710 715 720 Glu Ala Arg Ala Arg Leu Glu Leu Arg Glu Glu Ala Thr Lys Glu Asp 725 730 735 Ala Glu Asp Ile Val Glu Ile Met Lys Tyr Ser Met Leu Gly Thr Tyr 740 745 750 Ser Asp Glu Phe Gly Asn Leu Asp Phe Glu Arg Ser Gln His Gly Ser 755 760 765 Gly Met Ser Asn Arg Ser Thr Ala Lys Arg Phe Ile Ser Ala Leu Asn 770 775 780 Asn Val Ala Glu Arg Thr Tyr Asn Asn Ile Phe Gln Phe His Gln Leu 785 790 795 800 Arg Gln Ile Ala Lys Glu Leu Asn Ile Gln Val Ala Asp Phe Glu Asn 805 810 815 Phe Ile Gly Ser Leu Asn Asp Gln Gly Tyr Leu Leu Lys Lys Gly Pro 820 825 830 Lys Val Tyr Gln Leu Gln Thr Met 835 840 <210> 25 <211> 999 <212> PRT <213> Homo sapiens <400> 25 Met Glu Pro Arg Ala Ala Ala Ala Gly Glu Pro Glu Pro Pro Ala Ala 1 5 10 15 Ser Ser Ser Phe Gln Ala Arg Leu Trp Lys Asn Leu Gln Leu Gly Val 20 25 30 Gly Arg Ser Lys Gly Gly Gly Gly Gly Arg Ala Gly Gly Pro Glu Arg 35 40 45 Arg Thr Ala Asp Thr Pro Ser Pro Ser Pro Pro Pro Val Gly Thr 50 55 60 Gly Asn Ala Pro Ala Arg Gly Ser Gly Ala Gly Ser Arg Trp Ser Gly 65 70 75 80 Phe Lys Lys Arg Lys Gln Val Leu Asp Arg Val Phe Ser Ser Ser Gln 85 90 95 Pro Asn Leu Cys Cys Ser Ser Pro Glu Pro Leu Glu Pro Gly Gly Ala 100 105 110 Gly Arg Ala Glu Gln Gly Ser Thr Leu Arg Arg Arg Ile Arg Glu His 115 120 125 Leu Leu Pro Ala Val Lys Gly Pro Ala Ala Ala Ser Gly Ala Ala Gly 130 135 140 Gly Thr Pro Pro Gly Gly Arg Ser Pro Asp Ser Ala Pro Ser Ser Ser 145 150 155 160 Ser Ala Ser Ser Ser Leu Ser Ser Ser Pro Gln Pro Pro Pro Arg Gly 165 170 175 Asp Arg Ala Arg Asp Glu Gly Ala Arg Arg Gln Gly Pro Gly Ala His 180 185 190 Leu Cys His Gln Lys Ser Ser Ser Leu Pro Gly Thr Ala Cys Leu Glu 195 200 205 Gln Leu Leu Glu Pro Pro Pro Pro Ala Glu Pro Ala Arg Ser Pro 210 215 220 Ala Glu Ser Arg Ala Pro Glu Thr Gly Glu Glu His Gly Ser Ser Gln 225 230 235 240 Lys Ile Ile Asn Thr Ala Gly Thr Ser Asn Ala Glu Val Pro Leu Ala 245 250 255 Asp Pro Gly Met Tyr Gln Leu Asp Ile Thr Leu Arg Arg Gly Gln Ser 260 265 270 Leu Ala Ala Arg Asp Arg Gly Gly Thr Ser Asp Pro Tyr Val Lys Phe 275 280 285 Lys Ile Gly Gly Lys Glu Val Phe Arg Ser Lys Ile Ile His Lys Asn 290 295 300 Leu Asn Pro Val Trp Glu Glu Lys Ala Cys Ile Leu Val Asp His Leu 305 310 315 320 Arg Glu Pro Leu Tyr Ile Lys Val Phe Asp Tyr Asp Phe Gly Leu Gln 325 330 335 Asp Asp Phe Met Gly Ser Ala Phe Leu Asp Leu Thr Gln Leu Glu Leu 340 345 350 Asn Arg Pro Thr Asp Val Thr Leu Thr Leu Lys Asp Pro His Tyr Pro 355 360 365 Asp His Asp Leu Gly Ile Ile Leu Leu Ser Val Ile Leu Thr Pro Lys 370 375 380 Glu Gly Glu Ser Arg Asp Val Thr Met Leu Met Arg Lys Ser Trp Lys 385 390 395 400 Arg Ser Ser Lys Glu Leu Ser Glu Asn Glu Val Val Gly Ser Tyr Phe 405 410 415 Ser Val Lys Ser Leu Phe Trp Arg Thr Cys Gly Arg Pro Ala Leu Pro 420 425 430 Val Leu Gly Phe Cys Arg Ala Glu Leu Gln Asn Pro Tyr Cys Lys Asn 435 440 445 Val Gln Phe Gln Thr Gln Ser Leu Arg Leu Ser Asp Leu His Arg Lys 450 455 460 Ser His Leu Trp Arg Gly Ile Val Ser Ile Thr Leu Ile Glu Gly Arg 465 470 475 480 Asp Leu Lys Ala Met Asp Ser Asn Gly Leu Ser Asp Pro Tyr Val Lys 485 490 495 Phe Arg Leu Gly His Gln Lys Tyr Lys Ser Lys Ile Met Pro Lys Thr 500 505 510 Leu Asn Pro Gln Trp Arg Glu Gln Phe Asp Phe His Leu Tyr Glu Glu 515 520 525 Arg Gly Gly Val Ile Asp Ile Thr Ala Trp Asp Lys Asp Ala Gly Lys 530 535 540 Arg Asp Asp Phe Ile Gly Arg Cys Gln Val Asp Leu Ser Ala Leu Ser 545 550 555 560 Arg Glu Gln Thr His Lys Leu Glu Leu Gln Leu Glu Glu Gly Glu Gly 565 570 575 His Leu Val Leu Leu Val Thr Leu Thr Ala Ser Ala Thr Val Ser Ile 580 585 590 Ser Asp Leu Ser Val Asn Ser Leu Glu Asp Gln Lys Glu Arg Glu Glu 595 600 605 Ile Leu Lys Arg Tyr Ser Pro Leu Arg Ile Phe His Asn Leu Lys Asp 610 615 620 Val Gly Phe Leu Gln Val Lys Val Ile Arg Ala Glu Gly Leu Met Ala 625 630 635 640 Ala Asp Val Thr Gly Lys Ser Asp Pro Phe Cys Val Val Glu Leu Asn 645 650 655 Asn Asp Arg Leu Leu Thr His Thr Val Tyr Lys Asn Leu Asn Pro Glu 660 665 670 Trp Asn Lys Val Phe Thr Phe Asn Ile Lys Asp Ile His Ser Val Leu 675 680 685 Glu Val Thr Val Tyr Asp Glu Asp Arg Asp Arg Ser Ala Asp Phe Leu 690 695 700 Gly Lys Val Ala Ile Pro Leu Leu Ser Ile Gln Asn Gly Glu Gln Lys 705 710 715 720 Ala Tyr Val Leu Lys Asn Lys Gln Leu Thr Gly Pro Thr Lys Gly Val 725 730 735 Ile Tyr Leu Glu Ile Asp Val Ile Phe Asn Ala Val Lys Ala Ser Leu 740 745 750 Arg Thr Leu Ile Pro Lys Glu Gln Lys Tyr Ile Glu Glu Glu Asn Arg 755 760 765 Leu Ser Lys Gln Leu Leu Leu Arg Asn Phe Ile Arg Met Lys Arg Cys 770 775 780 Val Met Val Leu Val Asn Ala Ala Tyr Tyr Val Asn Ser Cys Phe Asp 785 790 795 800 Trp Asp Ser Pro Pro Arg Ser Leu Ala Ala Phe Val Leu Phe Leu Phe 805 810 815 Val Val Trp Asn Phe Glu Leu Tyr Met Ile Pro Leu Val Leu Leu Leu 820 825 830 Leu Leu Thr Trp Asn Tyr Phe Leu Ile Ile Ser Gly Lys Asp Asn Arg 835 840 845 Gln Arg Asp Thr Val Val Glu Asp Met Leu Glu Asp Glu Glu Glu Glu 850 855 860 Asp Asp Lys Asp Asp Lys Asp Ser Glu Lys Lys Gly Phe Ile Asn Lys 865 870 875 880 Ile Tyr Ala Ile Gln Glu Val Cys Val Ser Val Gln Asn Ile Leu Asp 885 890 895 Glu Val Ala Ser Phe Gly Glu Arg Ile Lys Asn Thr Phe Asn Trp Thr 900 905 910 Val Pro Phe Leu Ser Trp Leu Ala Ile Val Ala Leu Cys Val Phe Thr 915 920 925 Ala Ile Leu Tyr Cys Ile Pro Leu Arg Tyr Ile Val Leu Val Trp Gly 930 935 940 Ile Asn Lys Phe Thr Lys Lys Leu Arg Ser Pro Tyr Ala Ile Asp Asn 945 950 955 960 Asn Glu Leu Leu Asp Phe Leu Ser Arg Val Pro Ser Asp Val Gln Val 965 970 975 Val Gln Tyr Gln Glu Leu Lys Pro Asp Pro Ser His Ser Pro Tyr Lys 980 985 990 Arg Lys Lys Asn Asn Leu Gly 995 <210> 26 <211> 1581 <212> PRT <213> Homo sapiens <400> 26 Met Lys Ala Gln Gly Glu Thr Glu Glu Ser Glu Lys Leu Ser Lys Met 1 5 10 15 Ser Ser Leu Leu Glu Arg Leu His Ala Lys Phe Asn Gln Asn Arg Pro 20 25 30 Trp Ser Glu Thr Ile Lys Leu Val Arg Gln Val Met Glu Lys Arg Val 35 40 45 Val Met Ser Ser Gly Gly His Gln His Leu Val Ser Cys Leu Glu Thr 50 55 60 Leu Gln Lys Ala Leu Lys Val Thr Ser Leu Pro Ala Met Thr Asp Arg 65 70 75 80 Leu Glu Ser Ile Ala Arg Gln Asn Gly Leu Gly Ser His Leu Ser Ala 85 90 95 Ser Gly Thr Glu Cys Tyr Ile Thr Ser Asp Met Phe Tyr Val Glu Val 100 105 110 Gln Leu Asp Pro Ala Gly Gln Leu Cys Asp Val Lys Val Ala His His 115 120 125 Gly Glu Asn Pro Val Ser Cys Pro Glu Leu Val Gln Gln Leu Arg Glu 130 135 140 Lys Asn Phe Asp Glu Phe Ser Lys His Leu Lys Gly Leu Val Asn Leu 145 150 155 160 Tyr Asn Leu Pro Gly Asp Asn Lys Leu Lys Thr Lys Met Tyr Leu Ala 165 170 175 Leu Gln Ser Leu Glu Gln Asp Leu Ser Lys Met Ala Ile Met Tyr Trp 180 185 190 Lys Ala Thr Asn Ala Gly Pro Leu Asp Lys Ile Leu His Gly Ser Val 195 200 205 Gly Tyr Leu Thr Pro Arg Ser Gly Gly His Leu Met Asn Leu Lys Tyr 210 215 220 Tyr Val Ser Pro Ser Asp Leu Leu Asp Asp Lys Thr Ala Ser Pro Ile 225 230 235 240 Ile Leu His Glu Asn Asn Val Ser Arg Ser Leu Gly Met Asn Ala Ser 245 250 255 Val Thr Ile Glu Gly Thr Ser Ala Val Tyr Lys Leu Pro Ile Ala Pro 260 265 270 Leu Ile Met Gly Ser His Pro Val Asp Asn Lys Trp Thr Pro Ser Phe 275 280 285 Ser Ser Ile Thr Ser Ala Asn Ser Val Asp Leu Pro Ala Cys Phe Phe 290 295 300 Leu Lys Phe Pro Gln Pro Ile Pro Val Ser Arg Ala Phe Val Gln Lys 305 310 315 320 Leu Gln Asn Cys Thr Gly Ile Pro Leu Phe Glu Thr Gln Pro Thr Tyr 325 330 335 Ala Pro Leu Tyr Glu Leu Ile Thr Gln Phe Glu Leu Ser Lys Asp Pro 340 345 350 Asp Pro Ile Pro Leu Asn His Asn Met Arg Phe Tyr Ala Ala Leu Pro 355 360 365 Gly Gln Gln His Cys Tyr Phe Leu Asn Lys Asp Ala Pro Leu Pro Asp 370 375 380 Gly Arg Ser Leu Gln Gly Thr Leu Val Ser Lys Ile Thr Phe Gln His 385 390 395 400 Pro Gly Arg Val Pro Leu Ile Leu Asn Leu Ile Arg His Gln Val Ala 405 410 415 Tyr Asn Thr Leu Ile Gly Ser Cys Val Lys Arg Thr Ile Leu Lys Glu 420 425 430 Asp Ser Pro Gly Leu Leu Gln Phe Glu Val Cys Pro Leu Ser Glu Ser 435 440 445 Arg Phe Ser Val Ser Phe Gln His Pro Val Asn Asp Ser Leu Val Cys 450 455 460 Val Val Met Asp Val Gln Asp Ser Thr His Val Ser Cys Lys Leu Tyr 465 470 475 480 Lys Gly Leu Ser Asp Ala Leu Ile Cys Thr Asp Asp Phe Ile Ala Lys 485 490 495 Val Val Gln Arg Cys Met Ser Ile Pro Val Thr Met Arg Ala Ile Arg 500 505 510 Arg Lys Ala Glu Thr Ile Gln Ala Asp Thr Pro Ala Leu Ser Leu Ile 515 520 525 Ala Glu Thr Val Glu Asp Met Val Lys Lys Asn Leu Pro Ala Ser 530 535 540 Ser Pro Gly Tyr Gly Met Thr Thr Gly Asn Asn Pro Met Ser Gly Thr 545 550 555 560 Thr Thr Pro Thr Asn Thr Phe Pro Gly Gly Pro Ile Thr Thr Leu Phe 565 570 575 Asn Met Ser Met Ser Ile Lys Asp Arg His Glu Ser Val Gly His Gly 580 585 590 Glu Asp Phe Ser Lys Val Ser Gln Asn Pro Ile Leu Thr Ser Leu Leu 595 600 605 Gln Ile Thr Gly Asn Gly Gly Ser Thr Ile Gly Ser Ser Pro Thr Pro 610 615 620 Pro His His Thr Pro Pro Pro Val Ser Ser Met Ala Gly Asn Thr Lys 625 630 635 640 Asn His Pro Met Leu Met Asn Leu Leu Lys Asp Asn Pro Ala Gln Asp 645 650 655 Phe Ser Thr Leu Tyr Gly Ser Ser Pro Leu Glu Arg Gln Asn Ser Ser 660 665 670 Ser Gly Ser Pro Arg Met Glu Ile Cys Ser Gly Ser Asn Lys Thr Lys 675 680 685 Lys Lys Lys Ser Ser Arg Leu Pro Pro Glu Lys Pro Lys His Gln Thr 690 695 700 Glu Asp Asp Phe Gln Arg Glu Leu Phe Ser Met Asp Val Asp Ser Gln 705 710 715 720 Asn Pro Ile Phe Asp Val Asn Met Thr Ala Asp Thr Leu Asp Thr Pro 725 730 735 His Ile Thr Pro Ala Pro Ser Gln Cys Ser Thr Pro Pro Thr Thr Tyr 740 745 750 Pro Gln Pro Val Pro His Pro Gln Pro Ser Ile Gln Arg Met Val Arg 755 760 765 Leu Ser Ser Ser Asp Ser Ile Gly Pro Asp Val Thr Asp Ile Leu Ser 770 775 780 Asp Ile Ala Glu Glu Ala Ser Lys Leu Pro Ser Thr Ser Asp Asp Cys 785 790 795 800 Pro Ala Ile Gly Thr Pro Leu Arg Asp Ser Ser Ser Ser Gly His Ser 805 810 815 Gln Ser Thr Leu Phe Asp Ser Asp Val Phe Gln Thr Asn Asn Asn Glu 820 825 830 Asn Pro Tyr Thr Asp Pro Ala Asp Leu Ile Ala Asp Ala Ala Gly Ser 835 840 845 Pro Ser Ser Asp Ser Pro Thr Asn His Phe Phe His Asp Gly Val Asp 850 855 860 Phe Asn Pro Asp Leu Leu Asn Ser Gln Ser Gln Ser Gly Phe Gly Glu 865 870 875 880 Glu Tyr Phe Asp Glu Ser Ser Gln Ser Gly Asp Asn Asp Asp Phe Lys 885 890 895 Gly Phe Ala Ser Gln Ala Leu Asn Thr Leu Gly Val Pro Met Leu Gly 900 905 910 Gly Asp Asn Gly Glu Thr Lys Phe Lys Gly Asn Asn Gln Ala Asp Thr 915 920 925 Val Asp Phe Ser Ile Ile Ser Val Ala Gly Lys Ala Leu Ala Pro Ala 930 935 940 Asp Leu Met Glu His His Ser Gly Ser Gln Gly Pro Leu Leu Thr Thr 945 950 955 960 Gly Asp Leu Gly Lys Glu Lys Thr Gln Lys Arg Val Lys Glu Gly Asn 965 970 975 Gly Thr Ser Asn Ser Thr Leu Ser Gly Pro Gly Leu Asp Ser Lys Pro 980 985 990 Gly Lys Arg Ser Arg Thr Pro Ser Asn Asp Gly Lys Ser Lys Asp Lys 995 1000 1005 Pro Pro Lys Arg Lys Lys Ala Asp Thr Glu Gly Lys Ser Pro Ser His 1010 1015 1020 Ser Ser Ser Asn Arg Pro Phe Thr Pro Pro Thr Ser Thr Gly Gly Ser 1025 1030 1035 1040 Lys Ser Pro Gly Ser Ala Gly Arg Ser Gln Thr Pro Pro Gly Val Ala 1045 1050 1055 Thr Pro Pro Ile Pro Lys Ile Thr Ile Gln Ile Pro Lys Gly Thr Val 1060 1065 1070 Met Val Gly Lys Pro Ser Ser His Ser Gln Tyr Thr Ser Ser Ser Gly Ser 1075 1080 1085 Val Ser Ser Ser Gly Ser Lys Ser His His Ser His Ser Ser Ser Ser 1090 1095 1100 Ser Ser Ser Ala Ser Thr Ser Gly Lys Met Lys Ser Ser Lys Ser Glu 1105 1110 1115 1120 Gly Ser Ser Ser Ser Lys Leu Ser Ser Ser Met Tyr Ser Ser Gln Gly 1125 1130 1135 Ser Ser Gly Ser Ser Gln Ser Lys Asn Ser Ser Gln Ser Gly Gly Lys 1140 1145 1150 Pro Gly Ser Ser Pro Ile Thr Lys His Gly Leu Ser Ser Gly Ser Ser 1155 1160 1165 Ser Thr Lys Met Lys Pro Gln Gly Lys Pro Ser Ser Leu Met Asn Pro 1170 1175 1180 Ser Leu Ser Lys Pro Asn Ile Ser Pro Ser His Ser Arg Pro Pro Gly 1185 1190 1195 1200 Gly Ser Asp Lys Leu Ala Ser Pro Met Lys Pro Val Pro Gly Thr Pro 1205 1210 1215 Pro Ser Ser Lys Ala Lys Ser Pro Ile Ser Ser Gly Ser Gly Gly Ser 1220 1225 1230 His Met Ser Gly Thr Ser Ser Ser Ser Gly Met Lys Ser Ser Ser Gly 1235 1240 1245 Leu Gly Ser Ser Gly Ser Leu Ser Gln Lys Thr Pro Pro Ser Ser Asn 1250 1255 1260 Ser Cys Thr Ala Ser Ser Ser Ser Phe Ser Ser Ser Gly Ser Ser Met 1265 1270 1275 1280 Ser Ser Ser Gln Asn Gln His Gly Ser Ser Lys Gly Lys Ser Pro Ser 1285 1290 1295 Arg Asn Lys Lys Pro Ser Leu Thr Ala Val Ile Asp Lys Leu Lys His 1300 1305 1310 Gly Val Val Thr Ser Gly Pro Gly Gly Glu Asp Pro Leu Asp Gly Gln 1315 1320 1325 Met Gly Val Ser Thr Asn Ser Ser Ser His Pro Met Ser Ser Lys His 1330 1335 1340 Asn Met Ser Gly Gly Glu Phe Gln Gly Lys Arg Glu Lys Ser Asp Lys 1345 1350 1355 1360 Asp Lys Ser Lys Val Ser Thr Ser Gly Ser Ser Val Asp Ser Ser Lys 1365 1370 1375 Lys Thr Ser Glu Ser Lys Asn Val Gly Ser Thr Gly Val Ala Lys Ile 1380 1385 1390 Ile Ile Ser Lys His Asp Gly Gly Ser Pro Ser Ile Lys Ala Lys Val 1395 1400 1405 Thr Leu Gln Lys Pro Gly Glu Ser Ser Gly Glu Gly Leu Arg Pro Gln 1410 1415 1420 Met Ala Ser Ser Lys Asn Tyr Gly Ser Pro Leu Ile Ser Gly Ser Thr 1425 1430 1435 1440 Pro Lys His Glu Arg Gly Ser Pro Ser His Ser Lys Ser Pro Ala Tyr 1445 1450 1455 Thr Pro Gln Asn Leu Asp Ser Glu Ser Glu Ser Gly Ser Ser Ile Ala 1460 1465 1470 Glu Lys Ser Tyr Gln Asn Ser Pro Ser Ser Asp Asp Gly Ile Arg Pro 1475 1480 1485 Leu Pro Glu Tyr Ser Thr Glu Lys His Lys Lys His Lys Lys Glu Lys 1490 1495 1500 Lys Lys Val Lys Asp Lys Asp Arg Asp Arg Asp Arg Asp Lys Asp Arg 1505 1510 1515 1520 Asp Lys Lys Lys Ser His Ser Ile Lys Pro Glu Ser Trp Ser Lys Ser 1525 1530 1535 Pro Ile Ser Ser Asp Gln Ser Leu Ser Met Thr Ser Asn Thr Ile Leu 1540 1545 1550 Ser Ala Asp Arg Pro Ser Arg Leu Ser Pro Asp Phe Met Ile Gly Glu 1555 1560 1565 Glu Asp Asp Asp Leu Met Asp Val Ala Leu Ile Gly Asn 1570 1575 1580 <210> 27 <211> 1369 <212> PRT <213> Homo sapiens <400> 27 Met Ser Val Pro Val Ala Pro Lys Lys Ser Cys Tyr Thr Gln Leu Arg 1 5 10 15 Asp Asn Arg Asn Ala Ala Arg Asn Asn Asn Glu Ser Ile Leu Ser Leu 20 25 30 Gly Asp Thr Asn Ala Asn Gln Ile Met Leu Glu Val Ser Ser Ser His 35 40 45 Asp Glu Ser Lys Thr Cys Asp Leu Gly Asp Glu Ile Gly Asn Thr Asn 50 55 60 Ser Ser Glu Pro Glu Asn Arg Thr His Phe His Lys Glu Phe His Gln 65 70 75 80 Leu Gln Gly Phe Gly Lys Gly Ser Gln Ala Gly Ser Ala Ser Leu Lys 85 90 95 Asp Phe Arg Leu Ser Ser Thr Ile Gln Arg Glu Leu Asn Glu Glu His 100 105 110 Thr Val Glu Arg Gly Thr Asp Ser Leu Gln Thr Thr Arg Ser Ile Gln 115 120 125 Gly Pro Ser Leu Ser Ser Ser Trp Arg Asn Val Met Ser Glu Ala Ser Leu 130 135 140 Asp Val Leu Ala Lys Arg Asp Ala Glu Ile Pro Arg His Val Pro Lys 145 150 155 160 Asp Lys Leu Ala Lys Thr Leu Asp Asn Glu Glu Leu Arg Arg His Ser 165 170 175 Leu Glu Arg Ala Ser Ser Ser Val Ala Ala Val Gly Ser Leu Thr Pro 180 185 190 Gln His Pro Gln Pro Leu Ser Leu Asp Ser Arg Glu Ala Arg Gly Gln 195 200 205 Ile Pro Gly Gly Gly Glu Gly Pro Gln Lys Thr Leu Pro Asp His Ala 210 215 220 Val Pro Ala Ala Phe Pro Ala Thr Asp Ser Thr Ser Glu Gly Lys Ser 225 230 235 240 Val Arg His Pro Lys Pro Ser Thr Ser Glu Ser Lys Gln Ser Thr Pro 245 250 255 Ser Glu Thr Gln Thr Val Gly Ala His Val Leu Gln Val Cys Ser Glu 260 265 270 His Thr Ser His Ser Ala His Pro Glu Pro Ala Leu Asn Leu Thr Leu 275 280 285 Ala Ser Lys Glu Ile Pro Ser Lys Leu Glu Ala Gln Leu Gly Gln Gly 290 295 300 Lys Gly Glu Ala Lys Leu Asp Leu Lys Tyr Val Pro Arg Arg Val 305 310 315 320 Glu Gln Glu Gly Lys Ala Ala Gln Glu Gly Tyr Leu Gly Cys His Lys 325 330 335 Glu Glu Asn Leu Ser Ala Leu Glu Gly Arg Asp Pro Cys Gly Glu Ala 340 345 350 His Pro Glu Ala Thr Asp Ala Leu Gly His Leu Leu Asn Ser Asp Leu 355 360 365 His His Leu Gly Val Gly Arg Gly Asn Cys Glu Glu Lys Arg Gly Val 370 375 380 Asn Pro Gly Glu Gln Asp Ser Leu His Thr Thr Pro Lys Gln Gly Ser 385 390 395 400 Ala Ser Leu Gly Gly Ala Asp Asn Gln Pro Thr Gly Lys Ile Ser Pro 405 410 415 Cys Ala Gly Glu Lys Leu Gly Glu Arg Thr Ser Ser Ser Phe Ser Pro 420 425 430 Gly Asp Ser His Val Ala Phe Ile Pro Asn Asn Leu Thr Asp Ser Lys 435 440 445 Pro Leu Asp Val Ile Glu Glu Glu Arg Arg Leu Gly Ser Gly Asn Lys 450 455 460 Asp Ser Val Met Val Leu Val Phe Asn Pro Ser Val Gly Glu Asn Lys 465 470 475 480 Thr Glu Val Pro Glu Pro Leu Asp Pro Gln Ser Gly Arg Ser Glu Ala 485 490 495 Arg Glu Ser Lys Glu Val Thr Thr Ser Val Ala Glu Asn Arg Asn Leu 500 505 510 Leu Glu Asn Ala Asp Lys Ile Glu Ser Thr Ser Ala Arg Ala Asp Ser 515 520 525 Val Leu Asn Ile Pro Ala Pro Leu His Pro Glu Thr Thr Val Asn Met 530 535 540 Thr Tyr Gln Pro Thr Thr Pro Ser Ser Ser Phe Gln Asp Val Ser Val 545 550 555 560 Phe Gly Met Asp Ala Gly Ser Pro Leu Val Val Pro Pro Pro Thr Asp 565 570 575 Ser Ala Arg Leu Leu Asn Thr Ser Pro Lys Val Pro Asp Lys Asn Thr 580 585 590 Cys Pro Ser Gly Ile Pro Lys Pro Val Phe Thr His Ser Lys Asp Thr 595 600 605 Pro Ser Ser Gln Glu Gly Met Glu Asn Tyr Gln Val Glu Lys Thr Glu 610 615 620 Glu Arg Thr Glu Thr Lys Pro Ile Ile Met Pro Lys Pro Lys His Val 625 630 635 640 Arg Pro Lys Ile Ile Thr Tyr Ile Arg Arg Asn Pro Gln Ala Leu Gly 645 650 655 Gln Val Asp Ala Ser Leu Val Pro Val Gly Leu Pro Tyr Ala Pro Pro 660 665 670 Thr Cys Thr Met Pro Leu Pro His Glu Glu Lys Ala Ala Gly Gly Asp 675 680 685 Leu Lys Pro Ser Ala Asn Leu Tyr Glu Lys Phe Lys Pro Asp Leu Gln 690 695 700 Lys Pro Arg Val Phe Ser Ser Gly Leu Met Val Ser Gly Ile Lys Pro 705 710 715 720 Pro Gly His Pro Phe Ser Gln Met Ser Glu Lys Phe Leu Gln Glu Val 725 730 735 Thr Asp His Pro Gly Lys Glu Glu Phe Cys Ser Pro Pro Tyr Ala His 740 745 750 Tyr Glu Val Pro Pro Thr Phe Tyr Arg Ser Ala Met Leu Leu Lys Pro 755 760 765 Gln Leu Gly Leu Gly Ala Met Ser Arg Leu Pro Ser Ala Lys Ser Arg 770 775 780 Ile Leu Ile Ala Ser Gln Arg Ser Ser Ala Ser Ala Ile His Pro Pro 785 790 795 800 Gly Pro Ile Thr Thr Ala Thr Ser Leu Tyr Ser Ser Asp Pro Ser Ala 805 810 815 Asp Leu Lys Lys Ala Ser Ser Ser Asn Ala Ala Lys Ser Asn Leu Pro 820 825 830 Lys Ser Gly Leu Arg Pro Pro Gly Tyr Ser Arg Leu Pro Ala Ala Lys 835 840 845 Leu Ala Ala Phe Gly Phe Val Arg Ser Ser Ser Val Ser Ser Val Ser 850 855 860 Ser Thr Gln Ser Gly Asp Ser Ala Gln Pro Glu Gln Gly Arg Pro Ala 865 870 875 880 Thr Arg Ser Thr Phe Gly Asn Glu Glu Gln Pro Val Leu Lys Ala Ser 885 890 895 Leu Pro Ser Lys Asp Thr Pro Lys Gly Ala Gly Arg Val Ala Pro Pro 900 905 910 Ala Ser Ser Ser Val Thr Ala Pro Arg Arg Ser Leu Leu Pro Ala Pro 915 920 925 Lys Ser Thr Ser Thr Pro Ala Gly Thr Lys Lys Asp Ala Gln Lys Asp 930 935 940 Gln Asp Thr Asn Lys Pro Ala Val Ser Ser Pro Lys Arg Val Ala Ala 945 950 955 960 Ser Thr Thr Lys Leu His Ser Pro Gly Tyr Pro Lys Gln Arg Thr Ala 965 970 975 Ala Ala Arg Asn Gly Phe Pro Lys Pro Asp Pro Gln Ala Arg Glu 980 985 990 Ala Glu Arg Gln Leu Val Leu Arg Leu Lys Glu Arg Cys Glu Gln Gln 995 1000 1005 Thr Arg Gln Leu Gly Val Ala Gln Gly Glu Leu Lys Arg Ala Ile Cys 1010 1015 1020 Gly Phe Asp Ala Leu Ala Val Ala Thr Gln His Phe Phe Arg Lys Asn 1025 1030 1035 1040 Glu Ser Ala Leu Val Lys Glu Lys Glu Leu Ser Ile Glu Leu Ala Asn 1045 1050 1055 Ile Arg Asp Glu Val Ala Phe His Thr Ala Lys Cys Glu Lys Leu Gln 1060 1065 1070 Lys Glu Lys Glu Glu Leu Glu Arg Arg Phe Glu Asp Glu Val Lys Arg 1075 1080 1085 Leu Gly Trp Gln Gln Gln Ala Glu Leu Gln Glu Leu Glu Glu Arg Leu 1090 1095 1100 Gln Leu Gln Phe Glu Ala Glu Met Ala Arg Leu Gln Glu Glu His Gly 1105 1110 1115 1120 Asp Gln Leu Leu Ser Ile Arg Cys Gln His Gln Glu Gln Val Glu Asp 1125 1130 1135 Leu Thr Ala Ser His Asp Ala Ala Leu Leu Glu Met Glu Asn Asn His 1140 1145 1150 Thr Val Ala Ile Thr Ile Leu Gln Asp Asp His Asp His Lys Val Gln 1155 1160 1165 Glu Leu Met Ser Thr His Glu Leu Glu Lys Lys Glu Leu Glu Glu Asn 1170 1175 1180 Phe Glu Lys Leu Arg Leu Ser Leu Gln Asp Gln Val Asp Thr Leu Thr 1185 1190 1195 1200 Phe Gln Ser Gln Ser Leu Arg Asp Arg Ala Arg Arg Phe Glu Glu Ala 1205 1210 1215 Leu Arg Lys Asn Thr Glu Glu Gln Leu Glu Ile Ala Leu Ala Pro Tyr 1220 1225 1230 Gln His Leu Glu Glu Asp Met Lys Ser Leu Lys Gln Val Leu Glu Met 1235 1240 1245 Lys Asn Gln Gln Ile His Glu Gln Glu Lys Lys Ile Leu Glu Leu Glu 1250 1255 1260 Lys Leu Ala Glu Lys Asn Ile Ile Leu Glu Glu Lys Ile Gln Val Leu 1265 1270 1275 1280 Gln Gln Gln Asn Glu Asp Leu Lys Ala Arg Ile Asp Gln Asn Thr Val 1285 1290 1295 Val Thr Arg Gln Leu Ser Glu Glu Asn Ala Asn Leu Gln Glu Tyr Val 1300 1305 1310 Glu Lys Glu Thr Gln Glu Lys Lys Arg Leu Ser Arg Thr Asn Glu Glu 1315 1320 1325 Leu Leu Trp Lys Leu Gln Thr Gly Asp Pro Thr Ser Pro Ile Lys Leu 1330 1335 1340 Ser Pro Thr Ser Pro Val Tyr Arg Gly Ser Ser Ser Gly Pro Ser Ser 1345 1350 1355 1360 Pro Ala Arg Val Ser Thr Thr Pro Arg 1365 <210> 28 <211> 2385 <212> PRT <213> Homo sapiens <400> 28 Met Pro Val Leu Gly Val Ala Ser Lys Leu Arg Gln Pro Ala Val Gly 1 5 10 15 Ser Lys Pro Val His Thr Ala Leu Pro Ile Pro Asn Leu Gly Thr Thr 20 25 30 Gly Ser Gln His Cys Ser Ser Arg Pro Leu Glu Leu Thr Glu Thr Glu 35 40 45 Ser Ser Met Leu Ser Cys Gln Leu Ala Leu Lys Ser Thr Cys Glu Phe 50 55 60 Gly Glu Lys Lys Pro Leu Gln Gly Lys Ala Lys Glu Lys Glu Asp Ser 65 70 75 80 Lys Ile Tyr Thr Asp Trp Ala Asn His Tyr Leu Ala Lys Ser Gly His 85 90 95 Lys Arg Leu Ile Lys Asp Leu Gln Gln Asp Ile Ala Asp Gly Val Leu 100 105 110 Leu Ala Glu Ile Ile Gln Ile Ile Ala Asn Glu Lys Val Glu Asp Ile 115 120 125 Asn Gly Cys Pro Arg Ser Gln Ser Gln Met Ile Glu Asn Val Asp Val 130 135 140 Cys Leu Ser Phe Leu Ala Ala Arg Gly Val Asn Val Gln Gly Leu Ser 145 150 155 160 Ala Glu Glu Ile Arg Asn Gly Asn Leu Lys Ala Ile Leu Gly Leu Phe 165 170 175 Phe Ser Leu Ser Arg Tyr Lys Gln Gln Gln His His Gln Gln Gln Tyr 180 185 190 Tyr Gln Ser Leu Val Glu Leu Gln Gln Arg Val Thr His Ala Ser Pro 195 200 205 Pro Ser Glu Ala Ser Gln Ala Lys Thr Gln Gln Asp Met Gln Ser Ser 210 215 220 Leu Ala Ala Arg Tyr Ala Thr Gln Ser Asn His Ser Gly Ile Ala Thr 225 230 235 240 Ser Gln Lys Lys Pro Thr Arg Leu Pro Gly Pro Ser Arg Val Pro Ala 245 250 255 Ala Gly Ser Ser Ser Lys Val Gln Gly Ala Ser Asn Leu Asn Arg Arg 260 265 270 Ser Gln Ser Phe Asn Ser Ile Asp Lys Asn Lys Pro Pro Asn Tyr Ala 275 280 285 Asn Gly Asn Glu Lys Asp Ser Ser Lys Gly Pro Gln Ser Ser Ser Gly 290 295 300 Val Asn Gly Asn Val Gln Pro Pro Ser Thr Ala Gly Gln Pro Pro Ala 305 310 315 320 Ser Ala Ile Pro Ser Pro Ser Ala Ser Lys Pro Trp Arg Ser Lys Ser 325 330 335 Met Asn Val Lys His Ser Ala Thr Ser Thr Met Leu Thr Val Lys Gln 340 345 350 Ser Ser Thr Ala Thr Ser Pro Thr Pro Ser Ser Asp Arg Leu Lys Pro 355 360 365 Pro Val Ser Glu Gly Val Lys Thr Ala Pro Ser Gly Gln Lys Ser Met 370 375 380 Leu Glu Lys Phe Lys Leu Val Asn Ala Arg Thr Ala Leu Arg Pro Pro 385 390 395 400 Gln Pro Pro Ser Ser Gly Pro Ser Asp Gly Gly Lys Asp Asp Asp Ala 405 410 415 Phe Ser Glu Ser Gly Glu Met Glu Gly Phe Asn Ser Gly Leu Asn Ser 420 425 430 Gly Gly Ser Thr Asn Ser Ser Pro Lys Val Ser Pro Lys Leu Ala Pro 435 440 445 Pro Lys Ala Gly Ser Lys Asn Leu Ser Asn Lys Lys Ser Leu Leu Gln 450 455 460 Pro Lys Glu Lys Glu Glu Lys Asn Arg Asp Lys Asn Lys Val Cys Thr 465 470 475 480 Glu Lys Pro Val Lys Glu Glu Lys Asp Gln Val Thr Glu Met Ala Pro 485 490 495 Lys Lys Thr Ser Lys Ile Ala Ser Leu Ile Pro Lys Gly Ser Lys Thr 500 505 510 Thr Ala Ala Lys Lys Glu Ser Leu Ile Pro Ser Ser Ser Gly Ile Pro 515 520 525 Lys Pro Gly Ser Lys Val Pro Thr Val Lys Gln Thr Ile Ser Pro Gly 530 535 540 Ser Thr Ala Ser Lys Glu Ser Glu Lys Phe Arg Thr Thr Lys Gly Ser 545 550 555 560 Pro Ser Gln Ser Leu Ser Lys Pro Ile Thr Met Glu Lys Ala Ser Ala 565 570 575 Ser Ser Cys Pro Ala Pro Leu Glu Gly Arg Glu Ala Gly Gly Gln Ala Ser 580 585 590 Pro Ser Gly Ser Cys Thr Met Thr Val Ala Gln Ser Ser Gly Gln Ser 595 600 605 Thr Gly Asn Gly Ala Val Gln Leu Pro Gln Gln Gln Gln His Ser His 610 615 620 Pro Asn Thr Ala Thr Val Ala Pro Phe Ile Tyr Arg Ala His Ser Glu 625 630 635 640 Asn Glu Gly Thr Ala Leu Pro Ser Ala Asp Ser Cys Thr Ser Pro Thr 645 650 655 Lys Met Asp Leu Ser Tyr Ser Lys Thr Ala Lys Gln Cys Leu Glu Glu 660 665 670 Ile Ser Gly Glu Asp Pro Glu Thr Arg Arg Met Arg Thr Val Lys Asn 675 680 685 Ile Ala Asp Leu Arg Gln Asn Leu Glu Glu Thr Met Ser Ser Leu Arg 690 695 700 Gly Thr Gln Ile Ser His Ser Thr Leu Glu Thr Thr Phe Asp Ser Thr 705 710 715 720 Val Thr Thr Glu Val Asn Gly Arg Thr Ile Pro Asn Leu Thr Ser Arg 725 730 735 Pro Thr Pro Met Thr Trp Arg Leu Gly Gln Ala Cys Pro Arg Leu Gln 740 745 750 Ala Gly Asp Ala Pro Ser Leu Gly Ala Gly Tyr Pro Arg Ser Gly Thr 755 760 765 Ser Arg Phe Ile His Thr Asp Pro Ser Arg Phe Met Tyr Thr Thr Pro 770 775 780 Leu Arg Arg Ala Ala Val Ser Arg Leu Gly Asn Met Ser Gln Ile Asp 785 790 795 800 Met Ser Glu Lys Ala Ser Ser Asp Leu Asp Met Ser Ser Glu Val Asp 805 810 815 Val Gly Gly Tyr Met Ser Asp Gly Asp Ile Leu Gly Lys Ser Leu Arg 820 825 830 Thr Asp Asp Ile Asn Ser Gly Tyr Met Thr Asp Gly Gly Leu Asn Leu 835 840 845 Tyr Thr Arg Ser Leu Asn Arg Ile Pro Asp Thr Ala Thr Ser Arg Asp 850 855 860 Ile Ile Gln Arg Gly Val His Asp Val Thr Val Asp Ala Asp Ser Trp 865 870 875 880 Asp Asp Ser Ser Ser Val Ser Ser Gly Leu Ser Asp Thr Leu Asp Asn 885 890 895 Ile Ser Thr Asp Asp Leu Asn Thr Thr Ser Ser Val Ser Ser Tyr Ser 900 905 910 Asn Ile Thr Val Pro Ser Arg Lys Asn Thr Gln Leu Arg Thr Asp Ser 915 920 925 Glu Lys Arg Ser Thr Thr Asp Glu Thr Trp Asp Ser Pro Glu Glu Leu 930 935 940 Lys Lys Pro Glu Glu Asp Phe Asp Ser His Gly Asp Ala Gly Gly Lys 945 950 955 960 Trp Lys Thr Val Ser Ser Gly Leu Pro Glu Asp Pro Glu Lys Ala Gly 965 970 975 Gln Lys Ala Ser Leu Ser Val Ser Gln Thr Gly Ser Trp Arg Arg Gly 980 985 990 Met Ser Ala Gln Gly Gly Ala Pro Ser Arg Gln Lys Ala Gly Thr Ser 995 1000 1005 Ala Leu Lys Thr Pro Gly Lys Thr Asp Asp Ala Lys Ala Ser Glu Lys 1010 1015 1020 Gly Lys Ala Pro Leu Lys Gly Ser Ser Leu Gln Arg Ser Pro Ser Asp 1025 1030 1035 1040 Ala Gly Lys Ser Ser Gly Asp Glu Gly Lys Lys Pro Pro Ser Gly Ile 1045 1050 1055 Gly Arg Ser Thr Ala Thr Ser Ser Phe Gly Phe Lys Lys Pro Ser Gly 1060 1065 1070 Val Gly Ser Ser Ala Met Ile Thr Ser Ser Gly Ala Thr Ile Thr Ser 1075 1080 1085 Gly Ser Ala Thr Leu Gly Lys Ile Pro Lys Ser Ala Ala Ile Gly Gly 1090 1095 1100 Lys Ser Asn Ala Gly Arg Lys Thr Ser Leu Asp Gly Ser Gln Asn Gln 1105 1110 1115 1120 Asp Asp Val Val Leu His Val Ser Ser Lys Thr Thr Leu Gln Tyr Arg 1125 1130 1135 Ser Leu Pro Arg Pro Ser Lys Ser Ser Thr Ser Gly Ile Pro Gly Arg 1140 1145 1150 Gly Gly His Arg Ser Ser Thr Ser Ser Ile Asp Ser Asn Val Ser Ser 1155 1160 1165 Lys Ser Ala Gly Ala Thr Thr Ser Lys Leu Arg Glu Pro Thr Lys Ile 1170 1175 1180 Gly Ser Gly Arg Ser Ser Pro Val Thr Val Asn Gln Thr Asp Lys Glu 1185 1190 1195 1200 Lys Glu Lys Val Ala Val Ser Asp Ser Glu Ser Val Ser Leu Ser Gly 1205 1210 1215 Ser Pro Lys Ser Ser Pro Thr Ser Ala Ser Ala Cys Gly Ala Gln Gly 1220 1225 1230 Leu Arg Gln Pro Gly Ser Lys Tyr Pro Asp Ile Ala Ser Pro Thr Phe 1235 1240 1245 Arg Arg Leu Phe Gly Ala Lys Ala Gly Gly Lys Ser Ala Ser Ala Pro 1250 1255 1260 Asn Thr Glu Gly Val Lys Ser Ser Ser Val Met Pro Ser Pro Ser Thr 1265 1270 1275 1280 Thr Leu Ala Arg Gln Gly Ser Leu Glu Ser Pro Ser Ser Gly Thr Gly 1285 1290 1295 Ser Met Gly Ser Ala Gly Gly Leu Ser Gly Ser Ser Ser Pro Leu Phe 1300 1305 1310 Asn Lys Pro Ser Asp Leu Thr Thr Asp Val Ile Ser Leu Ser His Ser 1315 1320 1325 Leu Ala Ser Ser Pro Ala Ser Val His Ser Phe Thr Ser Gly Gly Leu 1330 1335 1340 Val Trp Ala Ala Asn Met Ser Ser Ser Ser Ala Gly Ser Lys Asp Thr 1345 1350 1355 1360 Pro Ser Tyr Gln Ser Met Thr Ser Leu His Thr Ser Ser Glu Ser Ile 1365 1370 1375 Asp Leu Pro Leu Ser His His Gly Ser Leu Ser Gly Leu Thr Thr Gly 1380 1385 1390 Thr His Glu Val Gln Ser Leu Leu Met Arg Thr Gly Ser Val Arg Ser 1395 1400 1405 Thr Leu Ser Glu Ser Met Gln Leu Asp Arg Asn Thr Leu Pro Lys Lys 1410 1415 1420 Gly Leu Arg Tyr Thr Pro Ser Ser Arg Gln Ala Asn Gln Glu Glu Gly 1425 1430 1435 1440 Lys Glu Trp Leu Arg Ser His Ser Thr Gly Gly Leu Gln Asp Thr Gly 1445 1450 1455 Asn Gln Ser Pro Leu Val Ser Pro Ser Ala Met Ser Ser Ser Ala Ala 1460 1465 1470 Gly Lys Tyr His Phe Ser Asn Leu Val Ser Pro Thr Asn Leu Ser Gln 1475 1480 1485 Phe Asn Leu Pro Gly Pro Ser Met Met Arg Ser Asn Ser Ile Pro Ala 1490 1495 1500 Gln Asp Ser Ser Phe Asp Leu Tyr Asp Asp Ser Gln Leu Cys Gly Ser 1505 1510 1515 1520 Ala Thr Ser Leu Glu Glu Arg Pro Arg Ala Ile Ser His Ser Gly Ser 1525 1530 1535 Phe Arg Asp Ser Met Glu Glu Val His Gly Ser Ser Leu Ser Leu Val 1540 1545 1550 Ser Ser Thr Ser Ser Leu Tyr Ser Thr Ala Glu Glu Lys Ala His Ser 1555 1560 1565 Glu Gln Ile His Lys Leu Arg Arg Glu Leu Val Ala Ser Gln Glu Lys 1570 1575 1580 Val Ala Thr Leu Thr Ser Gln Leu Ser Ala Asn Ala His Leu Val Ala 1585 1590 1595 1600 Ala Phe Glu Lys Ser Leu Gly Asn Met Thr Gly Arg Leu Gln Ser Leu 1605 1610 1615 Thr Met Thr Ala Glu Gln Lys Glu Ser Glu Leu Ile Glu Leu Arg Glu 1620 1625 1630 Thr Ile Glu Met Leu Lys Ala Gln Asn Ser Ala Ala Gln Ala Ala Ile 1635 1640 1645 Gln Gly Ala Leu Asn Gly Pro Asp His Pro Pro Lys Asp Leu Arg Ile 1650 1655 1660 Arg Arg Gln His Ser Ser Glu Ser Val Ser Ser Ile Asn Ser Ala Thr 1665 1670 1675 1680 Ser His Ser Ser Ile Gly Ser Gly Asn Asp Ala Asp Ser Lys Lys Lys 1685 1690 1695 Lys Lys Lys Asn Trp Val Asn Ser Arg Gly Ser Glu Leu Arg Ser Ser 1700 1705 1710 Phe Lys Gln Ala Phe Gly Lys Lys Lys Ser Thr Lys Pro Pro Ser Ser 1715 1720 1725 His Ser Asp Ile Glu Glu Leu Thr Asp Ser Ser Leu Pro Ala Ser Pro 1730 1735 1740 Lys Leu Pro His Asn Ala Gly Asp Cys Gly Ser Ala Ser Met Lys Pro 1745 1750 1755 1760 Ser Gln Ser Ala Ser Ala Ser Pro Leu Val Trp Pro Pro Lys Lys Arg 1765 1770 1775 Gln Asn Gly Pro Val Ile Tyr Lys His Arg Ser Arg Ile Cys Glu Cys 1780 1785 1790 Thr Glu Ala Glu Ala Glu Ile Ile Leu Gln Leu Lys Ser Glu Leu Arg 1795 1800 1805 Glu Lys Glu Leu Lys Leu Thr Asp Ile Arg Leu Glu Ala Leu Ser Ser 1810 1815 1820 Ala His His Leu Asp Gln Ile Arg Glu Ala Met Asn Arg Met Gln Asn 1825 1830 1835 1840 Glu Ile Glu Ile Leu Lys Ala Glu Asn Asp Arg Leu Lys Ala Glu Thr 1845 1850 1855 Gly Asn Thr Ala Lys Pro Thr Arg Pro Pro Ser Glu Ser Ser Ser Ser Ser 1860 1865 1870 Thr Ser Ser Ser Ser Ser Arg Gln Ser Leu Gly Leu Ser Leu Asn Asn 1875 1880 1885 Leu Asn Ile Thr Glu Ala Val Ser Ser Asp Ile Leu Leu Asp Asp Ala 1890 1895 1900 Gly Asp Ala Thr Gly His Lys Asp Gly Arg Ser Val Lys Ile Ile Val 1905 1910 1915 1920 Ser Ile Ser Lys Gly Tyr Gly Arg Ala Lys Asp Gln Lys Ser Gln Ala 1925 1930 1935 Tyr Leu Ile Gly Ser Ile Gly Val Ser Gly Lys Thr Lys Trp Asp Val 1940 1945 1950 Leu Asp Gly Val Ile Arg Arg Leu Phe Lys Glu Tyr Val Phe Arg Ile 1955 1960 1965 Asp Thr Ser Thr Ser Leu Gly Leu Ser Ser Asp Cys Ile Ala Ser Tyr 1970 1975 1980 Cys Ile Gly Asp Leu Ile Arg Ser His Asn Leu Glu Val Pro Glu Leu 1985 1990 1995 2000 Leu Pro Cys Gly Tyr Leu Val Gly Asp Asn Asn Ile Ile Thr Val Asn 2005 2010 2015 Leu Lys Gly Val Glu Glu Asn Ser Leu Asp Ser Phe Val Phe Asp Thr 2020 2025 2030 Leu Ile Pro Lys Pro Ile Thr Gln Arg Tyr Phe Asn Leu Leu Met Glu 2035 2040 2045 His His Arg Ile Ile Leu Ser Gly Pro Ser Gly Thr Gly Lys Thr Tyr 2050 2055 2060 Leu Ala Asn Lys Leu Ala Glu Tyr Val Ile Thr Lys Ser Gly Arg Lys 2065 2070 2075 2080 Lys Thr Glu Asp Ala Ile Ala Thr Phe Asn Val Asp His Lys Ser Ser 2085 2090 2095 Lys Glu Leu Gln Gln Tyr Leu Ala Asn Leu Ala Glu Gln Cys Ser Ala 2100 2105 2110 Asp Asn Asn Gly Val Glu Leu Pro Val Val Ile Ile Leu Asp Asn Leu 2115 2120 2125 His His Val Gly Ser Leu Ser Asp Ile Phe Asn Gly Phe Leu Asn Cys 2130 2135 2140 Lys Tyr Asn Lys Cys Pro Tyr Ile Ile Gly Thr Met Asn Gln Gly Val 2145 2150 2155 2160 Ser Ser Ser Pro Asn Leu Glu Leu His His Asn Phe Arg Trp Val Leu 2165 2170 2175 Cys Ala Asn His Thr Glu Pro Val Lys Gly Phe Leu Gly Arg Tyr Leu 2180 2185 2190 Arg Arg Lys Leu Ile Glu Ile Glu Ile Glu Arg Asn Ile Arg Asn Asn 2195 2200 2205 Asp Leu Val Lys Ile Ile Asp Trp Ile Pro Lys Thr Trp His His Leu 2210 2215 2220 Asn Ser Phe Leu Glu Thr His Ser Ser Ser Asp Val Thr Ile Gly Pro 2225 2230 2235 2240 Arg Leu Phe Leu Pro Cys Pro Met Asp Val Glu Gly Ser Arg Val Trp 2245 2250 2255 Phe Met Asp Leu Trp Asn Tyr Ser Leu Val Pro Tyr Ile Leu Glu Ala 2260 2265 2270 Val Arg Glu Gly Leu Gln Met Tyr Gly Lys Arg Thr Pro Trp Glu Asp 2275 2280 2285 Pro Ser Lys Trp Val Leu Asp Thr Tyr Pro Trp Ser Ser Ala Thr Leu 2290 2295 2300 Pro Gln Glu Ser Pro Ala Leu Leu Gln Leu Arg Pro Glu Asp Val Gly 2305 2310 2315 2320 Tyr Glu Ser Cys Thr Ser Thr Lys Glu Ala Thr Thr Ser Lys His Ile 2325 2330 2335 Pro Gln Thr Asp Thr Glu Gly Asp Pro Leu Met Asn Met Leu Met Lys 2340 2345 2350 Leu Gln Glu Ala Ala Asn Tyr Ser Ser Thr Gln Ser Cys Asp Ser Glu 2355 2360 2365 Ser Thr Ser His His Glu Asp Ile Leu Asp Ser Ser Leu Glu Ser Thr 2370 2375 2380 Leu 238 <210> 29 <211> 263 <212> PRT <213> Homo sapiens <400> 29 Met Leu Ser Ser Lys Gly Leu Thr Val Val Asp Val Tyr Gln Gly Trp 129 133 138 143 Cys Gly Pro Cys Lys Pro Val Val Ser Leu Phe Gln Lys Met Arg Ile 148 153 158 Glu Val Gly Leu Asp Leu Leu His Phe Ala Leu Ala Glu Ala Asp Arg 163 168 173 Leu Asp Val Leu Glu Lys Tyr Arg Gly Lys Cys Glu Pro Thr Phe Leu 178 183 188 Phe Tyr Ala Ile Lys Asp Glu Ala Leu Ser Asp Glu Asp Glu Cys Val 193 198 203 208 Ser His Gly Lys Asn Asn Gly Glu Asp Glu Asp Met Val Ser Ser Glu 213 218 223 Arg Thr Cys Thr Leu Ala Ile Ile Lys Pro Asp Ala Val Ala His Gly 228 233 238 Lys Thr Asp Glu Ile Ile Met Lys Ile Gln Glu Ala Gly Phe Glu Ile 243 248 253 Leu Thr Asn Glu Glu Arg Thr Met Thr Glu Ala Glu Val Arg Leu Phe 258 263 268 Tyr Gln His Lys Ala Gly Glu Glu Ala Phe Glu Lys Leu Val His His 273 278 283 288 Met Cys Ser Gly Pro Ser His Leu Leu Ile Leu Thr Arg Thr Glu Gly 293 298 303 Phe Glu Asp Val Val Thr Thr Trp Arg Thr Val Met Gly Pro Arg Asp 308 313 318 Pro Asn Val Ala Arg Arg Glu Gln Pro Glu Ser Leu Arg Ala Gln Tyr 323 328 333 Gly Thr Glu Met Pro Phe Asn Ala Val His Gly Ser Arg Asp Arg Glu 338 343 348 Asp Ala Asp Arg Glu Leu Ala Leu Leu Phe Pro Ser Leu Lys Phe Ser 353 358 363 368 Asp Lys Asp Thr Glu Ala Pro Gin Gly Glu Ser Ser Thr Gln Pro Arg 373 378 383 Leu Lys Ile Thr Asp Leu Asp 388 <210> 30 <211> 800 <212> PRT <213> Homo sapiens <400> 30 Met Lys Ala Arg Arg Asn Lys Lys Gln Ile Pro Ser Phe Arg Lys Leu 1 5 10 15 Ile Lys Thr Ser Lys Val Lys Leu Glu Asn Lys Leu Lys Asn Lys Gln 20 25 30 Phe Lys Gln Gln Ser Thr Leu Lys Lys Tyr Arg Lys Glu Gln Arg Lys 35 40 45 Leu Arg Gln Ala Val Lys Asp Ala Val Ser Lys Lys Pro Ile Pro Leu 50 55 60 Glu Asn Pro Lys Glu Lys Arg Pro Gly Lys Arg Ile Glu Arg Glu Glu 65 70 75 80 Glu Glu Glu Glu Glu Ala Leu Pro Leu Asp Met Met Asp Glu Asp Asp 85 90 95 Leu Gln Leu Met Lys Asp Leu Gly Gln Arg Val Ser Phe Leu Thr Arg 100 105 110 Asp Leu Ser Ser Ser Glu Pro Val His Ala Lys Lys Arg Lys His Glu 115 120 125 Arg Ile Ile Asp Lys Tyr Glu Lys Ile Pro Arg Thr Leu Gln Thr Ala 130 135 140 Pro Glu Lys Glu Leu Ile His Leu Leu Pro Ile Lys Asp Lys Ser Gly 145 150 155 160 Ile Ile Pro Gln Thr Arg Glu Lys Pro Val Thr Asp Ser Asn Lys Asp 165 170 175 Glu Glu Asp Gln Glu Glu Glu Arg Glu Leu Glu Glu Glu Ile Ile Glu 180 185 190 Asp Pro Ile Gln Glu Leu Thr Ile Glu Glu His Leu Ile Glu Arg Lys 195 200 205 Lys Lys Leu Gln Glu Lys Lys Met His Ile Ala Ala Leu Ala Ser Ala 210 215 220 Ile Leu Ser Asp Pro Glu Asn Asn Ile Lys Lys Leu Lys Glu Leu Arg 225 230 235 240 Ser Met Leu Met Glu Gln Asp Pro Asp Val Ala Val Thr Val Arg Lys 245 250 255 Leu Val Ile Val Ser Leu Met Glu Leu Phe Lys Asp Ile Thr Pro Ser 260 265 270 Tyr Lys Ile Arg Pro Leu Thr Glu Ala Glu Lys Ser Thr Lys Thr Arg 275 280 285 Lys Glu Thr Gln Lys Leu Arg Glu Phe Glu Glu Gly Leu Val Ser Gln 290 295 300 Tyr Lys Phe Tyr Leu Glu Asn Leu Glu Gln Met Val Lys Asp Trp Lys 305 310 315 320 Gln Arg Lys Leu Lys Lys Ser Asn Val Val Ser Leu Lys Ala Tyr Lys 325 330 335 Gly Leu Ala Glu Val Ala Val Lys Ser Leu Cys Glu Leu Leu Val Ala 340 345 350 Leu Pro His Phe Asn Phe His Asn Asn Ile Ile Val Leu Ile Val Pro 355 360 365 Leu Met Asn Asp Met Ser Lys Leu Ile Ser Glu Met Cys Cys Glu Ala 370 375 380 Val Lys Lys Leu Phe Lys Gln Asp Lys Leu Gly Gln Ala Ser Leu Gly 385 390 395 400 Val Ile Lys Val Ile Ser Gly Phe Val Lys Gly Arg Asn Tyr Glu Val 405 410 415 Arg Pro Glu Met Leu Lys Thr Phe Leu Cys Leu Arg Ile Lys Glu Val 420 425 430 Glu Val Lys Lys Asp Thr Glu Asp Ile Asn Lys Pro Lys Lys Phe Met 435 440 445 Thr Phe Lys Glu Lys Arg Lys Ser Leu Ser Arg Met Gln Arg Lys Trp 450 455 460 Lys Lys Ala Glu Glu Lys Leu Glu Arg Glu Leu Arg Glu Ala Glu Ala 465 470 475 480 Ser Glu Ser Thr Glu Lys Lys Leu Lys Leu His Thr Glu Thr Leu Asn 485 490 495 Ile Val Phe Val Thr Tyr Phe Arg Ile Leu Lys Lys Ala Gln Arg Ser 500 505 510 Pro Leu Leu Pro Ala Val Leu Glu Gly Leu Ala Lys Phe Ala His Leu 515 520 525 Ile Asn Val Glu Phe Phe Asp Asp Leu Leu Val Val Leu His Thr Leu 530 535 540 Ile Glu Ser Gly Asp Leu Ser Tyr Gln Glu Ser Leu His Cys Val Gln 545 550 555 560 Thr Ala Phe His Ile Leu Ser Gly Gln Gly Asp Val Leu Asn Ile Asp 565 570 575 Pro Leu Lys Phe Tyr Thr His Leu Tyr Lys Thr Leu Phe Lys Leu His 580 585 590 Ala Gly Ala Thr Asn Glu Gly Val Glu Ile Val Leu Gln Cys Leu Asp 595 600 605 Val Met Leu Thr Lys Arg Arg Lys Gln Val Ser Gln Gln Arg Ala Leu 610 615 620 Ala Phe Ile Lys Arg Leu Cys Thr Leu Ala Leu His Val Leu Pro Asn 625 630 635 640 Ser Ser Ile Gly Ile Leu Ala Thr Thr Arg Ile Leu Met His Thr Phe 645 650 655 Pro Lys Thr Asp Leu Leu Leu Asp Ser Glu Ser Gln Gly Ser Gly Val 660 665 670 Phe Leu Pro Glu Leu Asp Glu Pro Glu Tyr Cys Asn Ala Gln Asn Thr 675 680 685 Ala Leu Trp Glu Leu His Ala Leu Arg Arg His Tyr His Pro Ile Val 690 695 700 Gln Arg Phe Ala Ala His Leu Ile Ala Gly Ala Pro Ser Glu Gly Ser 705 710 715 720 Gly Ala Leu Lys Pro Glu Leu Ser Arg Arg Ser Ala Thr Glu Leu Phe 725 730 735 Glu Ala Tyr Ser Met Ala Glu Met Thr Phe Asn Pro Val Glu Ser 740 745 750 Ser Asn Pro Lys Ile Lys Gly Lys Phe Leu Gln Gly Asp Ser Phe Leu 755 760 765 Asn Glu Asp Leu Asn Gln Leu Ile Lys Arg Tyr Ser Ser Glu Val Ala 770 775 780 Thr Glu Ser Pro Leu Asp Phe Thr Lys Tyr Leu Lys Thr Ser Leu His 785 790 795 800 <210> 31 <211> 637 <212> PRT <213> Homo sapiens <400> 31 Met His Leu Arg Ile His Ala Arg Arg Ser Pro Pro Arg Arg Pro Ala 1 5 10 15 Trp Thr Leu Gly Ile Trp Phe Leu Phe Trp Gly Cys Ile Val Ser Ser 20 25 30 Val Trp Ser Ser Ser Asn Val Ala Ser Ser Ser Ser Thr Ser Ser Ser 35 40 45 Pro Gly Ser His Ser Gln His Glu His His Phe His Gly Ser Lys His 50 55 60 His Ser Val Pro Ile Ser Ile Tyr Arg Ser Pro Val Ser Leu Arg Gly 65 70 75 80 Gly His Ala Gly Ala Thr Tyr Ile Phe Gly Lys Ser Gly Gly Leu Ile 85 90 95 Leu Tyr Thr Trp Pro Ala Asn Asp Arg Pro Ser Thr Arg Ser Asp Arg 100 105 110 Leu Ala Val Gly Phe Ser Thr Thr Val Lys Asp Gly Ile Leu Val Arg 115 120 125 Ile Asp Ser Ala Pro Gly Leu Gly Asp Phe Leu Gln Leu His Ile Glu 130 135 140 Gln Gly Lys Ile Gly Val Val Phe Asn Ile Gly Thr Val Asp Ile Ser 145 150 155 160 Ile Lys Glu Glu Arg Thr Pro Val Asn Asp Gly Lys Tyr His Val Val 165 170 175 Arg Phe Thr Arg Asn Gly Gly Asn Ala Thr Leu Gln Val Asp Asn Trp 180 185 190 Pro Val Asn Glu His Tyr Pro Thr Gly Arg Gln Leu Thr Ile Phe Asn 195 200 205 Thr Gln Ala Gln Ile Ala Ile Gly Gly Lys Asp Lys Gly Arg Leu Phe 210 215 220 Gln Gly Gln Leu Ser Gly Leu Tyr Tyr Asp Gly Leu Lys Val Leu Asn 225 230 235 240 Met Ala Ala Glu Asn Asn Pro Asn Ile Lys Ile Asn Gly Ser Val Arg 245 250 255 Leu Val Gly Glu Val Pro Ser Ile Leu Gly Thr Thr Gln Thr Thr Ser 260 265 270 Met Pro Pro Glu Met Ser Thr Thr Val Met Glu Thr Thr Thr Met 275 280 285 Ala Thr Thr Thr Thr Arg Lys Asn Arg Ser Thr Ala Ser Ile Gln Pro 290 295 300 Thr Ser Asp Asp Leu Val Ser Ser Ala Glu Cys Ser Ser Asp Asp Glu 305 310 315 320 Asp Phe Val Glu Cys Glu Pro Ser Thr Gly Gly Glu Leu Val Ile Pro 325 330 335 Leu Leu Val Glu Asp Pro Leu Ala Thr Pro Pro Ile Ala Thr Arg Ala 340 345 350 Pro Ser Ile Thr Leu Pro Pro Thr Phe Arg Pro Leu Leu Thr Ile Ile 355 360 365 Glu Thr Thr Lys Asp Ser Leu Ser Met Thr Ser Glu Ala Gly Leu Pro 370 375 380 Cys Leu Ser Asp Gln Gly Ser Asp Gly Cys Asp Asp Asp Gly Leu Val 385 390 395 400 Ile Ser Gly Tyr Gly Ser Gly Glu Thr Phe Asp Ser Asn Leu Pro Pro 405 410 415 Thr Asp Asp Glu Asp Phe Tyr Thr Thr Phe Ser Leu Val Thr Asp Lys 420 425 430 Ser Leu Ser Thr Ser Ile Phe Glu Gly Gly Tyr Lys Ala His Ala Pro 435 440 445 Lys Trp Glu Ser Lys Asp Phe Arg Pro Asn Lys Val Ser Glu Thr Ser 450 455 460 Arg Thr Thr Thr Thr Ser Leu Ser Pro Glu Leu Ile Arg Phe Thr Ala 465 470 475 480 Ser Ser Ser Ser Gly Met Val Pro Lys Leu Pro Ala Gly Lys Met Asn 485 490 495 Asn Arg Asp Leu Lys Pro Gln Pro Asp Ile Val Leu Leu Pro Leu Pro 500 505 510 Thr Ala Tyr Glu Leu Asp Ser Thr Lys Leu Lys Ser Pro Leu Ile Thr 515 520 525 Ser Pro Met Phe Arg Asn Val Pro Thr Ala Asn Pro Thr Glu Pro Gly 530 535 540 Ile Arg Arg Val Pro Gly Ala Ser Glu Val Ile Arg Glu Ser Ser Ser Ser 545 550 555 560 Thr Thr Gly Met Val Val Gly Ile Val Ala Ala Ala Ala Ala Leu Cys Ile 565 570 575 Leu Ile Leu Leu Tyr Ala Met Tyr Lys Tyr Arg Asn Arg Asp Glu Gly 580 585 590 Ser Tyr Gln Val Asp Glu Thr Arg Asn Tyr Ile Ser Asn Ser Ala Gln 595 600 605 Ser Asn Gly Thr Leu Met Lys Glu Lys Gln Gln Ser Ser Lys Ser Gly 610 615 620 His Lys Lys Gln Lys Asn Lys Asp Arg Glu Tyr Tyr Val 625 630 635 <210> 32 <211> 1686 <212> PRT <213> Homo sapiens <400> 32 Met Ala Gln Ile Ser Ser Asn Ser Gly Phe Lys Glu Cys Pro Ser Ser 1 5 10 15 His Pro Glu Pro Thr Arg Ala Lys Asp Val Asp Lys Glu Glu Ala Leu 20 25 30 Gln Met Glu Ala Glu Ala Leu Ala Lys Leu Gln Lys Asp Arg Gln Val 35 40 45 Thr Asp Asn Gln Arg Gly Phe Glu Leu Ser Ser Ser Thr Arg Lys Lys 50 55 60 Ala Gln Val Tyr Asn Lys Gln Asp Tyr Asp Leu Met Val Phe Pro Glu 65 70 75 80 Ser Asp Ser Gln Lys Arg Ala Leu Asp Ile Asp Val Glu Lys Leu Thr 85 90 95 Gln Ala Glu Leu Glu Lys Leu Leu Leu Asp Asp Ser Phe Glu Thr Lys 100 105 110 Lys Thr Pro Val Leu Pro Val Thr Pro Ile Leu Ser Pro Ser Phe Ser 115 120 125 Ala Gln Leu Tyr Phe Arg Pro Thr Ile Gln Arg Gly Gln Trp Pro Pro 130 135 140 Gly Leu Pro Gly Pro Ser Thr Tyr Ala Leu Pro Ser Ile Tyr Pro Ser 145 150 155 160 Thr Tyr Ser Lys Gln Ala Ala Phe Gln Asn Gly Phe Asn Pro Arg Met 165 170 175 Pro Thr Phe Pro Ser Thr Glu Pro Ile Tyr Leu Ser Leu Pro Gly Gln 180 185 190 Ser Pro Tyr Phe Ser Tyr Pro Leu Thr Pro Ala Thr Pro Phe His Pro 195 200 205 Gln Gly Ser Leu Pro Ile Tyr Arg Pro Val Val Ser Thr Asp Met Ala 210 215 220 Lys Leu Phe Asp Lys Ile Ala Ser Thr Ser Glu Phe Leu Lys Asn Gly 225 230 235 240 Lys Ala Arg Thr Asp Leu Glu Ile Thr Asp Ser Lys Val Ser Asn Leu 245 250 255 Gln Val Ser Pro Lys Ser Glu Asp Ile Ser Lys Phe Asp Trp Leu Asp 260 265 270 Leu Asp Pro Leu Ser Lys Pro Lys Val Asp Asn Val Glu Val Leu Asp 275 280 285 His Glu Glu Glu Lys Asn Val Ser Ser Leu Leu Ala Lys Asp Pro Trp 290 295 300 Asp Ala Val Leu Leu Glu Glu Arg Ser Thr Ala Asn Cys His Leu Glu 305 310 315 320 Arg Lys Val Asn Gly Lys Ser Leu Ser Val Ala Thr Val Thr Arg Ser 325 330 335 Gln Ser Leu Asn Ile Arg Thr Thr Gln Leu Ala Lys Ala Gln Gly His 340 345 350 Ile Ser Gln Lys Asp Pro Asn Gly Thr Ser Ser Leu Pro Thr Gly Ser 355 360 365 Ser Leu Leu Gln Glu Val Glu Val Gln Asn Glu Glu Met Ala Ala Phe 370 375 380 Cys Arg Ser Ile Thr Lys Leu Lys Thr Lys Phe Pro Tyr Thr Asn His 385 390 395 400 Arg Thr Asn Pro Gly Tyr Leu Leu Ser Pro Val Thr Ala Gln Arg Asn 405 410 415 Ile Cys Gly Glu Asn Ala Ser Val Lys Val Ser Ile Asp Ile Glu Gly 420 425 430 Phe Gln Leu Pro Val Thr Phe Thr Cys Asp Val Ser Ser Thr Val Glu 435 440 445 Ile Ile Ile Met Gln Ala Leu Cys Trp Val His Asp Asp Leu Asn Gln 450 455 460 Val Asp Val Gly Ser Tyr Val Leu Lys Val Cys Gly Gln Glu Glu Val 465 470 475 480 Leu Gln Asn Asn His Cys Leu Gly Ser His Glu His Ile Gln Asn Cys 485 490 495 Arg Lys Trp Asp Thr Glu Ile Arg Leu Gln Leu Leu Thr Phe Ser Ala 500 505 510 Met Cys Gln Asn Leu Ala Arg Thr Ala Glu Asp Asp Glu Thr Pro Val 515 520 525 Asp Leu Asn Lys His Leu Tyr Gln Ile Glu Lys Pro Cys Lys Glu Ala 530 535 540 Met Thr Arg His Pro Val Glu Glu Leu Leu Asp Ser Tyr His Asn Gln 545 550 555 560 Val Glu Leu Ala Leu Gln Ile Glu Asn Gln His Arg Ala Val Asp Gln 565 570 575 Val Ile Lys Ala Val Arg Lys Ile Cys Ser Ala Leu Asp Gly Val Glu 580 585 590 Thr Leu Ala Ile Thr Glu Ser Val Lys Lys Leu Lys Arg Ala Val Asn 595 600 605 Leu Pro Arg Ser Lys Thr Ala Asp Val Thr Ser Leu Phe Gly Gly Glu 610 615 620 Asp Thr Ser Arg Ser Ser Thr Arg Gly Ser Leu Asn Pro Glu Asn Pro 625 630 635 640 Val Gln Val Ser Ile Asn Gln Leu Thr Ala Ala Ile Tyr Asp Leu Leu 645 650 655 Arg Leu His Ala Asn Ser Gly Arg Ser Pro Thr Asp Cys Ala Gln Ser 660 665 670 Ser Lys Ser Val Lys Glu Ala Trp Thr Thr Thr Glu Gln Leu Gln Phe 675 680 685 Thr Ile Phe Ala Ala His Gly Ile Ser Ser Asn Trp Val Ser Asn Tyr 690 695 700 Glu Lys Tyr Tyr Leu Ile Cys Ser Leu Ser His Asn Gly Lys Asp Leu 705 710 715 720 Phe Lys Pro Ile Gln Ser Lys Lys Val Gly Thr Tyr Lys Asn Phe Phe 725 730 735 Tyr Leu Ile Lys Trp Asp Glu Leu Ile Ile Phe Pro Ile Gln Ile Ser 740 745 750 Gln Leu Pro Leu Glu Ser Val Leu His Leu Thr Leu Phe Gly Ile Leu 755 760 765 Asn Gln Ser Ser Gly Ser Ser Pro Asp Ser Asn Lys Gln Arg Lys Gly 770 775 780 Pro Glu Ala Leu Gly Lys Val Ser Leu Pro Leu Phe Asp Phe Lys Arg 785 790 795 800 Phe Leu Thr Cys Gly Thr Lys Leu Leu Tyr Leu Trp Thr Ser Ser His 805 810 815 Thr Asn Ser Val Pro Gly Thr Val Thr Lys Lys Gly Tyr Val Met Glu 820 825 830 Arg Ile Val Leu Gln Val Asp Phe Pro Ser Pro Ala Phe Asp Ile Ile 835 840 845 Tyr Thr Thr Pro Gln Val Asp Arg Ser Ile Ile Gln Gln His Asn Leu 850 855 860 Glu Thr Leu Glu Asn Asp Ile Lys Gly Lys Leu Leu Asp Ile Leu His 865 870 875 880 Lys Asp Ser Ser Leu Gly Leu Ser Lys Glu Asp Lys Ala Phe Leu Trp 885 890 895 Glu Lys Arg Tyr Tyr Cys Phe Lys His Pro Asn Cys Leu Pro Lys Ile 900 905 910 Leu Ala Ser Ala Pro Asn Trp Lys Trp Val Asn Leu Ala Lys Thr Tyr 915 920 925 Ser Leu Leu His Gln Trp Pro Ala Leu Tyr Pro Leu Ile Ala Leu Glu 930 935 940 Leu Leu Asp Ser Lys Phe Ala Asp Gln Glu Val Arg Ser Leu Ala Val 945 950 955 960 Thr Trp Ile Glu Ala Ile Ser Asp Asp Glu Leu Thr Asp Leu Leu Pro 965 970 975 Gln Phe Val Gln Ala Leu Lys Tyr Glu Ile Tyr Leu Asn Ser Ser Leu 980 985 990 Val Gln Phe Leu Leu Ser Arg Ala Leu Gly Asn Ile Gln Ile Ala His 995 1000 1005 Asn Leu Tyr Trp Leu Leu Lys Asp Ala Leu His Asp Val Gln Phe Ser 1010 1015 1020 Thr Arg Tyr Glu His Val Leu Gly Ala Leu Leu Ser Val Gly Gly Lys 1025 1030 1035 1040 Arg Leu Arg Glu Glu Leu Leu Lys Gln Thr Lys Leu Val Gln Leu Leu 1045 1050 1055 Gly Gly Val Ala Glu Lys Val Arg Gln Ala Ser Gly Ser Ala Arg Gln 1060 1065 1070 Val Val Leu Gln Arg Ser Met Glu Arg Val Gln Ser Phe Phe Gln Lys 1075 1080 1085 Asn Lys Cys Arg Leu Pro Leu Lys Pro Ser Leu Val Ala Lys Glu Leu 1090 1095 1100 Asn Ile Lys Ser Cys Ser Phe Phe Ser Ser Asn Ala Val Pro Leu Lys 1105 1110 1115 1120 Val Thr Met Val Asn Ala Asp Pro Met Gly Glu Glu Ile Asn Val Met 1125 1130 1135 Phe Lys Val Gly Glu Asp Leu Arg Gln Asp Met Leu Ala Leu Gln Met 1140 1145 1150 Ile Lys Ile Met Asp Lys Ile Trp Leu Lys Glu Gly Leu Asp Leu Arg 1155 1160 1165 Met Val Ile Phe Lys Cys Leu Ser Thr Gly Arg Asp Arg Gly Met Val 1170 1175 1180 Glu Leu Val Pro Ala Ser Asp Thr Leu Arg Lys Ile Gln Val Glu Tyr 1185 1190 1195 1200 Gly Val Thr Gly Ser Phe Lys Asp Lys Pro Leu Ala Glu Trp Leu Arg 1205 1210 1215 Lys Tyr Asn Pro Ser Glu Glu Glu Tyr Glu Lys Ala Ser Glu Asn Phe 1220 1225 1230 Ile Tyr Ser Cys Ala Gly Cys Cys Val Ala Thr Tyr Val Leu Gly Ile 1235 1240 1245 Cys Asp Arg His Asn Asp Asn Ile Met Leu Arg Ser Thr Gly His Met 1250 1255 1260 Phe His Ile Asp Phe Gly Lys Phe Leu Gly His Ala Gln Met Phe Gly 1265 1270 1275 1280 Ser Phe Lys Arg Asp Arg Ala Pro Phe Val Leu Thr Ser Asp Met Ala 1285 1290 1295 Tyr Val Ile Asn Gly Gly Glu Lys Pro Thr Ile Arg Phe Gln Leu Phe 1300 1305 1310 Val Asp Leu Cys Cys Gln Ala Tyr Asn Leu Ile Arg Lys Gln Thr Asn 1315 1320 1325 Leu Phe Leu Asn Leu Leu Ser Leu Met Ile Pro Ser Gly Leu Pro Glu 1330 1335 1340 Leu Thr Ser Ile Gln Asp Leu Lys Tyr Val Arg Asp Ala Leu Gln Pro 1345 1350 1355 1360 Gln Thr Thr Asp Ala Glu Ala Thr Ile Phe Phe Thr Arg Leu Ile Glu 1365 1370 1375 Ser Ser Leu Gly Ser Ile Ala Thr Lys Phe Asn Phe Phe Ile His Asn 1380 1385 1390 Leu Ala Gln Leu Arg Phe Ser Gly Leu Pro Ser Asn Asp Glu Pro Ile 1395 1400 1405 Leu Ser Phe Ser Pro Lys Thr Tyr Ser Phe Arg Gln Asp Gly Arg Ile 1410 1415 1420 Lys Glu Val Ser Val Phe Thr Tyr His Lys Lys Tyr Asn Pro Asp Lys 1425 1430 1435 1440 His Tyr Ile Tyr Val Val Arg Ile Leu Arg Glu Gly Gln Ile Glu Pro 1445 1450 1455 Ser Phe Val Phe Arg Thr Phe Asp Glu Phe Gln Glu Leu His Asn Lys 1460 1465 1470 Leu Ser Ile Ile Phe Pro Leu Trp Lys Leu Pro Gly Phe Pro Asn Arg 1475 1480 1485 Met Val Leu Gly Arg Thr His Ile Lys Asp Val Ala Ala Lys Arg Lys 1490 1495 1500 Ile Glu Leu Asn Ser Tyr Leu Gln Ser Leu Met Asn Ala Ser Thr Asp 1505 1510 1515 1520 Val Ala Glu Cys Asp Leu Val Cys Thr Phe Phe His Pro Leu Leu Arg 1525 1530 1535 Asp Glu Lys Ala Glu Gly Ile Ala Arg Ser Ala Asp Ala Gly Ser Phe 1540 1545 1550 Ser Pro Thr Pro Gly Gln Ile Gly Gly Ala Val Lys Leu Ser Ile Ser 1555 1560 1565 Tyr Arg Asn Gly Thr Leu Phe Ile Met Val Met His Ile Lys Asp Leu 1570 1575 1580 Val Thr Glu Asp Gly Ala Asp Pro Asn Pro Tyr Val Lys Thr Tyr Leu 1585 1590 1595 1600 Leu Pro Asp Asn His Lys Thr Ser Lys Arg Lys Thr Lys Ile Ser Arg 1605 1610 1615 Lys Thr Arg Asn Pro Thr Phe Asn Glu Met Leu Val Tyr Ser Gly Tyr 1620 1625 1630 Ser Lys Glu Thr Leu Arg Gln Arg Glu Leu Gln Leu Ser Val Leu Ser 1635 1640 1645 Ala Glu Ser Leu Arg Glu Asn Phe Phe Leu Gly Gly Val Thr Leu Pro 1650 1655 1660 Leu Lys Asp Phe Asn Leu Ser Lys Glu Thr Val Lys Trp Tyr Gln Leu 1665 1670 1675 1680 Thr Ala Ala Thr Tyr Leu 1685 <210> 33 <211> 870 <212> PRT <213> Homo sapiens <400> 33 Met Asp Ser Thr Lys Glu Lys Cys Asp Ser Tyr Lys Asp Asp Leu Leu 1 5 10 15 Leu Arg Met Gly Leu Asn Asp Asn Lys Ala Gly Met Glu Gly Leu Asp 20 25 30 Lys Glu Lys Ile Asn Lys Ile Ile Met Glu Ala Thr Lys Gly Ser Arg 35 40 45 Phe Tyr Gly Asn Glu Leu Lys Lys Glu Lys Gln Val Asn Gln Arg Ile 50 55 60 Glu Asn Met Met Gln Gln Lys Ala Gln Ile Thr Ser Gln Gln Leu Arg 65 70 75 80 Lys Ala Gln Leu Gln Val Asp Arg Phe Ala Met Glu Leu Glu Gln Ser 85 90 95 Arg Asn Leu Ser Asn Thr Ile Val His Ile Asp Met Asp Ala Phe Tyr 100 105 110 Ala Ala Val Glu Met Arg Asp Asn Pro Glu Leu Lys Asp Lys Pro Ile 115 120 125 Ala Val Gly Ser Met Ser Met Leu Ser Thr Ser Asn Tyr His Ala Arg 130 135 140 Arg Phe Gly Val Arg Ala Ala Met Pro Gly Phe Ile Ala Lys Arg Leu 145 150 155 160 Cys Pro Gln Leu Ile Ile Val Pro Asn Phe Asp Lys Tyr Arg Ala 165 170 175 Val Ser Lys Glu Val Lys Glu Ile Leu Ala Asp Tyr Asp Pro Asn Phe 180 185 190 Met Ala Met Ser Leu Asp Glu Ala Tyr Leu Asn Ile Thr Lys His Leu 195 200 205 Glu Glu Arg Gln Asn Trp Pro Glu Asp Lys Arg Arg Tyr Phe Ile Lys 210 215 220 Met Gly Ser Ser Val Glu Asn Asp Asn Pro Gly Lys Glu Val Asn Lys 225 230 235 240 Leu Ser Glu His Glu Arg Ser Ile Ser Pro Leu Leu Phe Glu Glu Ser 245 250 255 Pro Ser Asp Val Gln Pro Pro Gly Asp Pro Phe Gln Val Asn Phe Glu 260 265 270 Glu Gln Asn Asn Pro Gln Ile Leu Gln Asn Ser Val Val Phe Gly Thr 275 280 285 Ser Ala Gln Glu Val Val Lys Glu Ile Arg Phe Arg Ile Glu Gln Lys 290 295 300 Thr Thr Leu Thr Ala Ser Ala Gly Ile Ala Pro Asn Thr Met Leu Ala 305 310 315 320 Lys Val Cys Ser Asp Lys Asn Lys Pro Asn Gly Gln Tyr Gln Ile Leu 325 330 335 Pro Asn Arg Gln Ala Val Met Asp Phe Ile Lys Asp Leu Pro Ile Arg 340 345 350 Lys Val Ser Gly Ile Gly Lys Val Thr Glu Lys Met Leu Lys Ala Leu 355 360 365 Gly Ile Ile Thr Cys Thr Glu Leu Tyr Gln Gln Arg Ala Leu Leu Ser 370 375 380 Leu Leu Phe Ser Glu Thr Ser Trp His Tyr Phe Leu His Ile Ser Leu 385 390 395 400 Gly Leu Gly Ser Thr His Leu Thr Arg Asp Gly Glu Arg Lys Ser Met 405 410 415 Ser Val Glu Arg Thr Phe Ser Glu Ile Asn Lys Ala Glu Glu Gln Tyr 420 425 430 Ser Leu Cys Gln Glu Leu Cys Ser Glu Leu Ala Gln Asp Leu Gln Lys 435 440 445 Glu Arg Leu Lys Gly Arg Thr Val Thr Ile Lys Leu Lys Asn Val Asn 450 455 460 Phe Glu Val Lys Thr Arg Ala Ser Thr Val Ser Ser Val Val Ser Thr 465 470 475 480 Ala Glu Glu Ile Phe Ala Ile Ala Lys Glu Leu Leu Lys Thr Glu Ile 485 490 495 Asp Ala Asp Phe Pro His Pro Leu Arg Leu Arg Leu Met Gly Val Arg 500 505 510 Ile Ser Ser Phe Pro Asn Glu Glu Asp Arg Lys His Gln Gln Arg Ser 515 520 525 Ile Ile Gly Phe Leu Gln Ala Gly Asn Gln Ala Leu Ser Ala Thr Glu 530 535 540 Cys Thr Leu Glu Lys Thr Asp Lys Asp Lys Phe Val Lys Pro Leu Glu 545 550 555 560 Met Ser His Lys Lys Ser Phe Phe Asp Lys Lys Arg Ser Glu Arg Lys 565 570 575 Trp Ser His Gln Asp Thr Phe Lys Cys Glu Ala Val Asn Lys Gln Ser 580 585 590 Phe Gln Thr Ser Gln Pro Phe Gln Val Leu Lys Lys Lys Met Asn Glu 595 600 605 Asn Leu Glu Ile Ser Glu Asn Ser Asp Asp Cys Gln Ile Leu Thr Cys 610 615 620 Pro Val Cys Phe Arg Ala Gln Gly Cys Ile Ser Leu Glu Ala Leu Asn 625 630 635 640 Lys His Val Asp Glu Cys Leu Asp Gly Pro Ser Ile Ser Glu Asn Phe 645 650 655 Lys Met Phe Ser Cys Ser His Val Ser Ala Thr Lys Val Asn Lys Lys 660 665 670 Glu Asn Val Pro Ala Ser Ser Leu Cys Glu Lys Gln Asp Tyr Glu Ala 675 680 685 His Pro Lys Ile Lys Glu Ile Ser Ser Val Asp Cys Ile Ala Leu Val 690 695 700 Asp Thr Ile Asp Asn Ser Ser Lys Ala Glu Ser Ile Asp Ala Leu Ser 705 710 715 720 Asn Lys His Ser Lys Glu Glu Cys Ser Ser Leu Pro Ser Lys Ser Phe 725 730 735 Asn Ile Glu His Cys His Gln Asn Ser Ser Ser Thr Val Ser Leu Glu 740 745 750 Asn Glu Asp Val Gly Ser Phe Arg Gln Glu Tyr Arg Gln Pro Tyr Leu 755 760 765 Cys Glu Val Lys Thr Gly Gln Ala Leu Val Cys Pro Val Cys Asn Val 770 775 780 Glu Gln Lys Thr Ser Asp Leu Thr Leu Phe Asn Val His Val Asp Val 785 790 795 800 Cys Leu Asn Lys Ser Phe Ile Gln Glu Leu Arg Lys Asp Lys Phe Asn 805 810 815 Pro Val Asn Gln Pro Lys Glu Ser Ser Arg Ser Thr Gly Ser Ser Ser 820 825 830 Gly Val Gln Lys Ala Val Thr Arg Thr Lys Arg Pro Gly Leu Met Thr 835 840 845 Lys Tyr Ser Thr Ser Lys Lys Ile Lys Pro Asn Asn Pro Lys His Thr 850 855 860 Leu Asp Ile Phe Phe Lys 865 870 <210> 34 <211> 762 <212> PRT <213> Homo sapiens <400> 34 Met Gly Asn Gly Ser Val Lys Pro Lys His Ser Lys His Pro Asp Gly 1 5 10 15 His Ser Gly Asn Leu Thr Thr Asp Ala Leu Arg Asn Lys Val Thr Glu 20 25 30 Leu Glu Arg Glu Leu Arg Arg Lys Asp Ala Glu Ile Gln Glu Arg Glu 35 40 45 Tyr His Leu Lys Glu Leu Arg Glu Gln Leu Ser Lys Gln Thr Val Ala 50 55 60 Ile Ala Glu Leu Thr Glu Glu Leu Gln Asn Lys Cys Ile Gln Leu Asn 65 70 75 80 Lys Leu Gln Asp Val Val His Met Gln Gly Gly Ser Pro Leu Gln Ala 85 90 95 Ser Pro Asp Lys Val Pro Leu Glu Val His Arg Lys Thr Ser Gly Leu 100 105 110 Val Ser Leu His Ser Arg Arg Gly Ala Lys Ala Gly Val Ser Ala Glu 115 120 125 Pro Thr Thr Arg Thr Tyr Asp Leu Asn Lys Pro Pro Glu Phe Ser Phe 130 135 140 Glu Lys Ala Arg Val Arg Lys Asp Ser Ser Glu Lys Lys Leu Ile Thr 145 150 155 160 Asp Ala Leu Asn Lys Asn Gln Phe Leu Lys Arg Leu Asp Pro Gln Gln 165 170 175 Ile Lys Asp Met Val Glu Cys Met Tyr Gly Arg Asn Tyr Gln Gln Gly 180 185 190 Ser Tyr Ile Ile Lys Gln Gly Glu Pro Gly Asn His Ile Phe Val Leu 195 200 205 Ala Glu Gly Arg Leu Glu Val Phe Gln Gly Glu Lys Leu Leu Ser Ser 210 215 220 Ile Pro Met Trp Thr Thr Phe Gly Glu Leu Ala Ile Leu Tyr Asn Cys 225 230 235 240 Thr Arg Thr Ala Ser Val Lys Ala Ile Thr Asn Val Lys Thr Trp Ala 245 250 255 Leu Asp Arg Glu Val Phe Gln Asn Ile Met Arg Arg Thr Ala Gln Ala 260 265 270 Arg Asp Glu Gln Tyr Arg Asn Phe Leu Arg Ser Val Ser Leu Leu Lys 275 280 285 Asn Leu Pro Glu Asp Lys Leu Thr Lys Ile Ile Asp Cys Leu Glu Val 290 295 300 Glu Tyr Tyr Asp Lys Gly Asp Tyr Ile Ile Arg Glu Gly Glu Glu Gly 305 310 315 320 Ser Thr Phe Phe Ile Leu Ala Lys Gly Lys Val Lys Val Thr Gln Ser 325 330 335 Thr Glu Gly His Asp Gln Pro Gln Leu Ile Lys Thr Leu Gln Lys Gly 340 345 350 Glu Tyr Phe Gly Glu Lys Ala Leu Ile Ser Asp Asp Val Arg Ser Ala 355 360 365 Asn Ile Ile Ala Glu Glu Asn Asp Val Ala Cys Leu Val Ile Asp Arg 370 375 380 Glu Thr Phe Asn Gln Thr Val Gly Thr Phe Glu Glu Leu Gln Lys Tyr 385 390 395 400 Leu Glu Gly Tyr Val Ala Asn Leu Asn Arg Asp Asp Glu Lys Arg His 405 410 415 Ala Lys Arg Ser Met Ser Asn Trp Lys Leu Ser Lys Ala Leu Ser Leu 420 425 430 Glu Met Ile Gln Leu Lys Glu Lys Val Ala Arg Phe Ser Ser Ser Ser Ser 435 440 445 Pro Phe Gln Asn Leu Glu Ile Ile Ala Thr Leu Gly Val Gly Gly Phe 450 455 460 Gly Arg Val Glu Leu Val Lys Val Lys Asn Glu Asn Val Ala Phe Ala 465 470 475 480 Met Lys Cys Ile Arg Lys Lys His Ile Val Asp Thr Lys Gln Gln Glu 485 490 495 His Val Tyr Ser Glu Lys Arg Ile Leu Glu Glu Leu Cys Ser Pro Phe 500 505 510 Ile Val Lys Leu Tyr Arg Thr Phe Lys Asp Asn Lys Tyr Val Tyr Met 515 520 525 Leu Leu Glu Ala Cys Leu Gly Gly Glu Leu Trp Ser Ile Leu Arg Asp 530 535 540 Arg Gly Ser Phe Asp Glu Pro Thr Ser Lys Phe Cys Val Ala Cys Val 545 550 555 560 Thr Glu Ala Phe Asp Tyr Leu His Arg Leu Gly Ile Ile Tyr Arg Asp 565 570 575 Leu Lys Pro Glu Asn Leu Ile Leu Asp Ala Glu Gly Tyr Leu Lys Leu 580 585 590 Val Asp Phe Gly Phe Ala Lys Lys Ile Gly Ser Gly Gln Lys Thr Trp 595 600 605 Thr Phe Cys Gly Thr Pro Glu Tyr Val Ala Pro Glu Val Ile Leu Asn 610 615 620 Lys Gly His Asp Phe Ser Val Asp Phe Trp Ser Leu Gly Ile Leu Val 625 630 635 640 Tyr Glu Leu Leu Thr Gly Asn Pro Pro Phe Ser Gly Val Asp Gln Met 645 650 655 Met Thr Tyr Asn Leu Ile Leu Lys Gly Ile Glu Lys Met Asp Phe Pro 660 665 670 Arg Lys Ile Thr Arg Arg Pro Glu Asp Leu Ile Arg Arg Leu Cys Arg 675 680 685 Gln Asn Pro Thr Glu Arg Leu Gly Asn Leu Lys Asn Gly Ile Asn Asp 690 695 700 Ile Lys Lys His Arg Trp Leu Asn Gly Phe Asn Trp Glu Gly Leu Lys 705 710 715 720 Ala Arg Ser Leu Pro Ser Pro Leu Gln Arg Glu Leu Lys Gly Pro Ile 725 730 735 Asp His Ser Tyr Phe Asp Lys Tyr Pro Pro Glu Lys Gly Met Pro Pro 740 745 750 Asp Glu Leu Ser Gly Trp Asp Lys Asp Phe 755 760 <210> 35 <211> 985 <212> PRT <213> Homo sapiens <400> 35 Met Ile Arg His Ala Gly Ala Pro Ala Arg Gly Asp Pro Thr Gly Pro 1 5 10 15 Val Pro Val Val Gly Lys Gly Glu Glu Glu Glu Glu Glu Asp Gly Met 20 25 30 Arg Leu Cys Leu Pro Ala Asn Pro Lys Asn Cys Leu Pro His Arg Arg 35 40 45 Gly Ile Ser Ile Leu Glu Lys Leu Ile Lys Thr Cys Pro Val Trp Leu 50 55 60 Gln Leu Ser Leu Gly Gln Ala Glu Val Ala Arg Ile Leu His Arg Val 65 70 75 80 Val Ala Gly Met Phe Leu Val Arg Arg Asp Ser Ser Ser Lys Gln Leu 85 90 95 Val Leu Cys Val His Phe Pro Ser Leu Asn Glu Ser Ser Ala Glu Val 100 105 110 Leu Glu Tyr Thr Ile Lys Glu Glu Lys Ser Ile Leu Tyr Leu Glu Gly 115 120 125 Ser Ala Leu Val Phe Glu Asp Ile Phe Arg Leu Ile Ala Phe Tyr Cys 130 135 140 Val Ser Arg Asp Leu Leu Pro Phe Thr Leu Arg Leu Pro Gln Ala Ile 145 150 155 160 Leu Glu Ala Ser Ser Phe Thr Asp Leu Glu Thr Ile Ala Asn Leu Gly 165 170 175 Leu Gly Phe Trp Asp Ser Ser Leu Asn Pro Pro Gln Glu Arg Gly Lys 180 185 190 Pro Ala Glu Pro Pro Arg Asp Arg Ala Pro Gly Phe Pro Leu Val Ser 195 200 205 Ser Leu Arg Pro Thr Ala His Asp Ala Asn Cys Ala Cys Glu Ile Glu 210 215 220 Leu Ser Val Gly Asn Asp Arg Leu Trp Phe Val Asn Pro Ile Phe Ile 225 230 235 240 Glu Asp Cys Ser Ser Ala Leu Pro Thr Asp Gln Pro Pro Leu Gly Asn 245 250 255 Cys Pro Ala Arg Pro Leu Pro Pro Thr Ser Asp Ala Thr Ser Pro Thr 260 265 270 Ser Arg Trp Ala Pro Arg Arg Pro Pro Pro Pro Pro Val Leu Pro 275 280 285 Leu Gln Pro Cys Ser Pro Ala Gln Pro Pro Val Leu Pro Ala Leu Ala 290 295 300 Pro Ala Pro Ala Cys Pro Leu Pro Thr Ser Pro Pro Val Pro Ala Pro 305 310 315 320 His Val Thr Pro His Ala Pro Gly Pro Pro Asp His Pro Asn Gln Pro 325 330 335 Pro Met Met Thr Cys Glu Arg Leu Pro Cys Pro Thr Ala Gly Leu Gly 340 345 350 Pro Leu Arg Glu Glu Ala Met Lys Pro Gly Ala Ala Ser Ser Pro Leu 355 360 365 Gln Gln Val Pro Ala Pro Pro Leu Pro Ala Lys Lys Asn Leu Pro Thr 370 375 380 Ala Pro Pro Arg Arg Arg Val Ser Glu Arg Val Ser Leu Glu Asp Gln 385 390 395 400 Ser Pro Gly Met Ala Ala Glu Gly Asp Gln Leu Ser Leu Pro Pro Gln 405 410 415 Gly Thr Ser Asp Gly Pro Glu Asp Thr Pro Arg Glu Ser Thr Glu Gln 420 425 430 Gly Gln Asp Thr Glu Val Lys Ala Ser Asp Pro His Ser Met Pro Glu 435 440 445 Leu Pro Arg Thr Ala Lys Gln Pro Val Pro Pro Pro Arg Lys Lys 450 455 460 Arg Ile Ser Arg Gln Leu Ala Ser Thr Leu Pro Ala Pro Leu Glu Asn 465 470 475 480 Ala Glu Leu Cys Thr Gln Ala Met Ala Leu Glu Thr Pro Thr Pro Gly 485 490 495 Pro Pro Arg Glu Gly Gln Ser Pro Ala Ser Gln Ala Gly Thr Gln His 500 505 510 Pro Pro Ala Gln Ala Thr Ala His Ser Gln Ser Ser Pro Glu Phe Lys 515 520 525 Gly Ser Leu Ala Ser Leu Ser Asp Ser Leu Gly Val Ser Val Met Ala 530 535 540 Thr Asp Gln Asp Ser Tyr Ser Thr Ser Ser Thr Glu Glu Glu Leu Glu 545 550 555 560 Gln Phe Ser Ser Pro Ser Val Lys Lys Lys Pro Ser Met Ile Leu Gly 565 570 575 Lys Ala Arg His Arg Leu Ser Phe Ala Ser Phe Ser Ser Met Phe His 580 585 590 Ala Phe Leu Ser Asn Asn Arg Lys Leu Tyr Lys Lys Val Val Glu Leu 595 600 605 Ala Gln Asp Lys Gly Ser Tyr Phe Gly Ser Leu Val Gln Asp Tyr Lys 610 615 620 Val Tyr Ser Leu Glu Met Met Ala Arg Gln Thr Ser Ser Thr Glu Met 625 630 635 640 Leu Gln Glu Ile Arg Thr Met Met Thr Gln Leu Lys Ser Tyr Leu Leu 645 650 655 Gln Ser Thr Glu Leu Lys Ala Leu Val Asp Pro Ala Leu His Ser Glu 660 665 670 Glu Glu Leu Glu Ala Ile Val Glu Ser Ala Leu Tyr Lys Cys Val Leu 675 680 685 Lys Pro Leu Lys Glu Ala Ile Asn Ser Cys Leu His Gln Ile His Ser 690 695 700 Lys Asp Gly Ser Leu Gln Gln Leu Lys Glu Asn Gln Leu Val Ile Leu 705 710 715 720 Ala Thr Thr Thr Thr Asp Leu Gly Val Thr Thr Ser Val Pro Glu Val 725 730 735 Pro Met Met Glu Lys Ile Leu Gln Lys Phe Thr Ser Met His Lys Ala 740 745 750 Tyr Ser Pro Glu Lys Lys Ile Ser Ile Leu Leu Lys Thr Cys Lys Leu 755 760 765 Ile Tyr Asp Ser Met Ala Leu Gly Asn Pro Gly Lys Pro Tyr Gly Ala 770 775 780 Asp Asp Phe Leu Pro Val Leu Met Tyr Val Leu Ala Arg Ser Asn Leu 785 790 795 800 Thr Glu Met Leu Leu Asn Val Glu Tyr Met Met Glu Leu Met Asp Pro 805 810 815 Ala Leu Gln Leu Gly Glu Gly Ser Tyr Tyr Leu Thr Thr Thr Tyr Gly 820 825 830 Ala Leu Glu His Ile Lys Ser Tyr Asp Lys Ile Thr Val Thr Arg Gln 835 840 845 Leu Ser Val Glu Val Gln Asp Ser Ile His Arg Trp Glu Arg Arg Arg 850 855 860 Thr Leu Asn Lys Ala Arg Ala Ser Arg Ser Ser Val Gln Asp Phe Ile 865 870 875 880 Cys Val Ser Tyr Leu Glu Pro Glu Gln Gln Ala Arg Thr Leu Ala Ser 885 890 895 Arg Ala Asp Thr Gln Ala Gln Ala Leu Cys Ala Gln Cys Ala Glu Lys 900 905 910 Phe Ala Val Glu Arg Pro Gln Ala His Arg Leu Phe Val Leu Val Asp 915 920 925 Gly Arg Cys Phe Gln Leu Ala Asp Asp Ala Leu Pro His Cys Ile Lys 930 935 940 Gly Tyr Leu Leu Arg Ser Glu Pro Lys Arg Asp Phe His Phe Val Tyr 945 950 955 960 Arg Pro Leu Asp Gly Gly Gly Gly Gly Gly Gly Gly Ser Pro Pro Cys 965 970 975 Leu Val Val Arg Glu Pro Asn Phe Leu 980 985 <210> 36 <211> 971 <212> PRT <213> Homo sapiens <400> 36 Met Gly Val Ala Gly Arg Asn Arg Pro Gly Ala Ala Trp Ala Val Leu 1 5 10 15 Leu Leu Leu Leu Leu Leu Pro Pro Leu Leu Leu Leu Ala Gly Ala Val 20 25 30 Pro Pro Gly Arg Gly Arg Ala Ala Gly Pro Gln Glu Asp Val Asp Glu 35 40 45 Cys Ala Gln Gly Leu Asp Asp Cys His Ala Asp Ala Leu Cys Gln Asn 50 55 60 Thr Pro Thr Ser Tyr Lys Cys Ser Cys Lys Pro Gly Tyr Gln Gly Glu 65 70 75 80 Gly Arg Gln Cys Glu Asp Ile Asp Glu Cys Gly Asn Glu Leu Asn Gly 85 90 95 Gly Cys Val His Asp Cys Leu Asn Ile Pro Gly Asn Tyr Arg Cys Thr 100 105 110 Cys Phe Asp Gly Phe Met Leu Ala His Asp Gly His Asn Cys Leu Asp 115 120 125 Val Asp Glu Cys Leu Glu Asn Asn Gly Gly Cys Gln His Thr Cys Val 130 135 140 Asn Val Met Gly Ser Tyr Glu Cys Cys Cys Lys Glu Gly Phe Phe Leu 145 150 155 160 Ser Asp Asn Gln His Thr Cys Ile His Arg Ser Glu Glu Gly Leu Ser 165 170 175 Cys Met Asn Lys Asp His Gly Cys Ser His Ile Cys Lys Glu Ala Pro 180 185 190 Arg Gly Ser Val Ala Cys Glu Cys Arg Pro Gly Phe Glu Leu Ala Lys 195 200 205 Asn Gln Arg Asp Cys Ile Leu Thr Cys Asn His Gly Asn Gly Gly Cys 210 215 220 Gln His Ser Cys Asp Asp Thr Ala Asp Gly Pro Glu Cys Ser Cys His 225 230 235 240 Pro Gln Tyr Lys Met His Thr Asp Gly Arg Ser Cys Leu Glu Arg Glu 245 250 255 Asp Thr Val Leu Glu Val Thr Glu Ser Asn Thr Thr Ser Val Val Asp 260 265 270 Gly Asp Lys Arg Val Lys Arg Arg Leu Leu Met Glu Thr Cys Ala Val 275 280 285 Asn Asn Gly Gly Cys Asp Arg Thr Cys Lys Asp Thr Ser Thr Gly Val 290 295 300 His Cys Ser Cys Pro Val Gly Phe Thr Leu Gln Leu Asp Gly Lys Thr 305 310 315 320 Cys Lys Asp Ile Asp Glu Cys Gln Thr Arg Asn Gly Gly Cys Asp His 325 330 335 Phe Cys Lys Asn Ile Val Gly Ser Phe Asp Cys Gly Cys Lys Lys Gly 340 345 350 Phe Lys Leu Leu Thr Asp Glu Lys Ser Cys Gln Asp Val Asp Glu Cys 355 360 365 Ser Leu Asp Arg Thr Cys Asp His Ser Cys Ile Asn His Pro Gly Thr 370 375 380 Phe Ala Cys Ala Cys Asn Arg Gly Tyr Thr Leu Tyr Gly Phe Thr His 385 390 395 400 Cys Gly Asp Thr Asn Glu Cys Ser Ile Asn Asn Gly Gly Cys Gln Gln 405 410 415 Val Cys Val Asn Thr Val Gly Ser Tyr Glu Cys Gln Cys His Pro Gly 420 425 430 Tyr Lys Leu His Trp Asn Lys Lys Asp Cys Val Glu Val Lys Gly Leu 435 440 445 Leu Pro Thr Ser Val Ser Pro Arg Val Ser Leu His Cys Gly Lys Ser 450 455 460 Gly Gly Gly Asp Gly Cys Phe Leu Arg Cys His Ser Gly Ile His Leu 465 470 475 480 Ser Ser Gly Leu Gln Gly Ala Tyr Ser Val Thr Cys Gly Ser Ser Ser Ser 485 490 495 Pro Leu Arg Asn Lys Gln Gln Lys Ser Asn Asp Ser Ala Phe Gly Asp 500 505 510 Val Thr Thr Ile Arg Thr Ser Val Thr Phe Lys Leu Asn Glu Gly Lys 515 520 525 Cys Ser Leu Lys Asn Ala Glu Leu Phe Pro Glu Gly Leu Arg Pro Ala 530 535 540 Leu Pro Glu Lys His Ser Ser Val Lys Glu Ser Phe Arg Tyr Val Asn 545 550 555 560 Leu Thr Cys Ser Ser Gly Lys Gln Val Pro Gly Ala Pro Gly Arg Pro 565 570 575 Ser Thr Pro Lys Glu Met Phe Ile Thr Val Glu Phe Glu Leu Glu Thr 580 585 590 Asn Gln Lys Glu Val Thr Ala Ser Cys Asp Leu Ser Cys Ile Val Lys 595 600 605 Arg Thr Glu Lys Arg Leu Arg Lys Ala Ile Arg Thr Leu Arg Lys Ala 610 615 620 Val His Arg Glu Gln Phe His Leu Gln Leu Ser Gly Met Asn Leu Asp 625 630 635 640 Val Ala Lys Lys Pro Pro Arg Thr Ser Glu Arg Gln Ala Glu Ser Cys 645 650 655 Gly Val Gly Gln Gly His Ala Glu Asn Gln Cys Gly Leu Cys Gln Pro 660 665 670 Gly Glu Tyr Ser Ala Asp Gly Phe Ala Pro Cys Gln Leu Cys Ala Leu 675 680 685 Gly Thr Phe Gln Pro Glu Ala Gly Arg Thr Ser Cys Phe Pro Cys Gly 690 695 700 Gly Gly Leu Ala Thr Lys His Gln Gly Ala Thr Ser Phe Gln Asp Cys 705 710 715 720 Glu Thr Arg Val Gln Cys Ser Pro Gly His Phe Tyr Asn Thr Thr Thr 725 730 735 His Arg Cys Ile Arg Cys Pro Val Gly Thr Tyr Gln Pro Glu Phe Gly 740 745 750 Lys Asn Asn Cys Val Ser Cys Pro Gly Asn Thr Thr Thr Asp Phe Asp 755 760 765 Gly Ser Thr Asn Ile Thr Gln Cys Lys Asn Arg Arg Cys Gly Gly Glu 770 775 780 Leu Gly Asp Phe Thr Gly Tyr Ile Glu Ser Pro Asn Tyr Pro Gly Asn 785 790 795 800 Tyr Pro Ala Asn Thr Glu Cys Thr Trp Thr Ile Asn Pro Pro Lys 805 810 815 Arg Arg Ile Leu Ile Val Val Pro Glu Ile Phe Leu Pro Ile Glu Asp 820 825 830 Asp Cys Gly Asp Tyr Leu Val Met Arg Lys Thr Ser Ser Ser Asn Ser 835 840 845 Val Thr Thr Tyr Glu Thr Cys Gln Thr Tyr Glu Arg Pro Ile Ala Phe 850 855 860 Thr Ser Arg Ser Lys Lys Leu Trp Ile Gln Phe Lys Ser Asn Glu Gly 865 870 875 880 Asn Ser Ala Arg Gly Phe Gln Val Pro Tyr Val Thr Tyr Asp Glu Asp 885 890 895 Tyr Gln Glu Leu Ile Glu Asp Ile Val Arg Asp Gly Arg Leu Tyr Ala 900 905 910 Ser Glu Asn His Gln Glu Ile Leu Lys Asp Lys Lys Leu Ile Lys Ala 915 920 925 Leu Phe Asp Val Leu Ala His Pro Gln Asn Tyr Phe Lys Tyr Thr Ala 930 935 940 Gln Glu Ser Arg Glu Met Phe Pro Arg Ser Phe Ile Arg Leu Leu Arg 945 950 955 960 Ser Lys Val Ser Arg Phe Leu Arg Pro Tyr Lys 965 970 <210> 37 <211> 782 <212> PRT <213> Homo sapiens <400> 37 Met Leu Gln Gln Pro Gly Pro Arg Pro Gly Arg Gln Gln Pro Ser Gly 1 5 10 15 Asp Arg Asp Ala Cys Arg Leu His Pro Gln Gly Arg Pro Pro Ala Leu 20 25 30 Pro Thr Met Ile Pro Ala Ala Ser Ser Thr Pro Pro Gly Asp Ala Leu 35 40 45 Phe Pro Ser Val Ala Pro Gln Asp Phe Trp Arg Ser Gln Val Thr Gly 50 55 60 Tyr Ser Gly Ser Val Thr Arg His Leu Ser His Arg Ala Asn Asn Phe 65 70 75 80 Lys Arg His Pro Lys Arg Arg Lys Cys Ile Arg Pro Ser Pro Pro Pro 85 90 95 Pro Pro Asn Thr Pro Cys Pro Leu Glu Leu Val Asp Phe Gly Asp Leu 100 105 110 His Pro Gln Arg Ser Phe Arg Glu Leu Leu Phe Asn Gly Cys Ile Leu 115 120 125 Phe Gly Ile Glu Phe Ser Tyr Ala Met Glu Thr Ala Tyr Val Thr Pro 130 135 140 Val Leu Leu Gln Met Gly Leu Pro Asp Gln Leu Tyr Ser Leu Val Trp 145 150 155 160 Phe Ile Ser Pro Ile Leu Gly Phe Leu Leu Gln Pro Leu Leu Gly Ala 165 170 175 Trp Ser Asp Arg Cys Thr Ser Arg Phe Gly Arg Arg Arg Pro Phe Ile 180 185 190 Leu Val Leu Ala Ile Gly Ala Leu Leu Gly Leu Ser Leu Leu Leu Asn 195 200 205 Gly Arg Asp Ile Gly Ile Ala Leu Ala Asp Val Thr Gly Asn His Lys 210 215 220 Trp Gly Leu Leu Leu Thr Val Cys Gly Val Val Leu Met Asp Phe Ser 225 230 235 240 Ala Asp Ser Ala Asp Asn Pro Ser His Ala Tyr Met Met Asp Val Cys 245 250 255 Ser Pro Ala Asp Gln Asp Arg Gly Leu Asn Ile His Ala Leu Leu Ala 260 265 270 Gly Leu Gly Gly Gly Phe Gly Tyr Val Val Gly Gly Ile His Trp Asp 275 280 285 Lys Thr Gly Phe Gly Arg Ala Leu Gly Gly Gln Leu Arg Val Ile Tyr 290 295 300 Leu Phe Thr Ala Val Thr Leu Ser Val Thr Thr Val Leu Thr Leu Val 305 310 315 320 Ser Ile Pro Glu Arg Pro Leu Arg Pro Pro Ser Glu Lys Arg Ala Ala 325 330 335 Met Lys Ser Pro Ser Leu Pro Leu Pro Pro Ser Pro Pro Val Leu Pro 340 345 350 Glu Glu Gly Pro Gly Asp Ser Leu Pro Ser His Thr Ala Thr Asn Phe 355 360 365 Ser Ser Pro Ile Ser Pro Pro Ser Pro Leu Thr Pro Lys Tyr Gly Ser 370 375 380 Phe Ile Ser Arg Asp Ser Ser Leu Thr Gly Ile Ser Glu Phe Ala Ser 385 390 395 400 Ser Phe Gly Thr Ala Asn Ile Asp Ser Val Leu Ile Asp Cys Phe Thr 405 410 415 Gly Gly His Asp Ser Tyr Leu Ala Ile Pro Gly Ser Val Pro Arg Pro 420 425 430 Pro Ile Ser Val Ser Phe Pro Arg Ala Pro Asp Gly Phe Tyr Arg Gln 435 440 445 Asp Arg Gly Leu Leu Glu Gly Arg Glu Gly Ala Leu Thr Ser Gly Cys 450 455 460 Asp Gly Asp Ile Leu Arg Val Gly Ser Leu Asp Thr Ser Lys Pro Arg 465 470 475 480 Ser Ser Gly Ile Leu Lys Arg Pro Gln Thr Leu Ala Ile Pro Asp Ala 485 490 495 Ala Gly Gly Gly Gly Pro Glu Thr Ser Arg Arg Arg Asn Val Thr Phe 500 505 510 Ser Gln Gln Val Ala Asn Ile Leu Leu Asn Gly Val Lys Tyr Glu Ser 515 520 525 Glu Leu Thr Gly Ser Ser Glu Arg Ala Glu Gln Pro Leu Ser Val Gly 530 535 540 Arg Leu Cys Ser Thr Ile Cys Asn Met Pro Lys Ala Leu Arg Thr Leu 545 550 555 560 Cys Val Asn His Phe Leu Gly Trp Leu Ser Phe Glu Gly Met Leu Leu 565 570 575 Phe Tyr Thr Asp Phe Met Gly Glu Val Val Phe Gln Gly Asp Pro Lys 580 585 590 Ala Pro His Thr Ser Glu Ala Tyr Gln Lys Tyr Asn Ser Gly Val Thr 595 600 605 Met Gly Cys Trp Gly Met Cys Ile Tyr Ala Phe Ser Ala Ala Phe Tyr 610 615 620 Ser Ala Ile Leu Glu Lys Leu Glu Glu Phe Leu Ser Val Arg Thr Leu 625 630 635 640 Tyr Phe Ile Ala Tyr Leu Ala Phe Gly Leu Gly Thr Gly Leu Ala Thr 645 650 655 Leu Ser Arg Asn Leu Tyr Val Val Leu Ser Leu Cys Ile Thr Tyr Gly 660 665 670 Ile Leu Phe Ser Thr Leu Cys Thr Leu Pro Tyr Ser Leu Leu Cys Asp 675 680 685 Tyr Tyr Gln Ser Lys Lys Phe Ala Gly Ser Ser Ala Asp Gly Thr Arg 690 695 700 Arg Gly Met Gly Val Asp Ile Ser Leu Leu Ser Cys Gln Tyr Phe Leu 705 710 715 720 Ala Gln Ile Leu Val Ser Leu Val Leu Gly Pro Leu Thr Ser Ala Val 725 730 735 Gly Ser Ala Asn Gly Val Met Tyr Phe Ser Ser Leu Val Ser Phe Leu 740 745 750 Gly Cys Leu Tyr Ser Ser Leu Phe Val Ile Tyr Glu Ile Pro Ser Ser 755 760 765 Asp Ala Ala Asp Glu Glu His Arg Pro Leu Leu Leu Asn Val 770 775 780 <210> 38 <211> 2214 <212> PRT <213> Homo sapiens <400> 38 Met Ala Thr Arg Ser Ser Arg Arg Glu Ser Arg Leu Pro Phe Leu Phe 1 5 10 15 Thr Leu Val Ala Leu Leu Pro Pro Gly Ala Leu Cys Glu Val Trp Thr 20 25 30 Gln Arg Leu His Gly Gly Ser Ala Pro Leu Pro Gln Asp Arg Gly Phe 35 40 45 Leu Val Val Gln Gly Asp Pro Arg Glu Leu Arg Leu Trp Ala Arg Gly 50 55 60 Asp Ala Arg Gly Ala Ser Arg Ala Asp Glu Lys Pro Leu Arg Arg Lys 65 70 75 80 Arg Ser Ala Ala Leu Gln Pro Glu Pro Ile Lys Val Tyr Gly Gln Val 85 90 95 Ser Leu Asn Asp Ser His Asn Gln Met Val Val His Trp Ala Gly Glu 100 105 110 Lys Ser Asn Val Ile Val Ala Leu Ala Arg Asp Ser Leu Ala Leu Ala 115 120 125 Arg Pro Lys Ser Ser Asp Val Tyr Val Ser Tyr Asp Tyr Gly Lys Ser 130 135 140 Phe Lys Lys Ile Ser Asp Lys Leu Asn Phe Gly Leu Gly Asn Arg Ser 145 150 155 160 Glu Ala Val Ile Ala Gln Phe Tyr His Ser Pro Ala Asp Asn Lys Arg 165 170 175 Tyr Ile Phe Ala Asp Ala Tyr Ala Gln Tyr Leu Trp Ile Thr Phe Asp 180 185 190 Phe Cys Asn Thr Leu Gln Gly Phe Ser Ile Pro Phe Arg Ala Ala Asp 195 200 205 Leu Leu Leu His Ser Lys Ala Ser Asn Leu Leu Leu Gly Phe Asp Arg 210 215 220 Ser His Pro Asn Lys Gln Leu Trp Lys Ser Asp Asp Phe Gly Gln Thr 225 230 235 240 Trp Ile Met Ile Gln Glu His Val Lys Ser Phe Ser Trp Gly Ile Asp 245 250 255 Pro Tyr Asp Lys Pro Asn Thr Ile Tyr Ile Glu Arg His Glu Pro Ser 260 265 270 Gly Tyr Ser Thr Val Phe Arg Ser Thr Asp Phe Phe Gln Ser Arg Glu 275 280 285 Asn Gln Glu Val Ile Leu Glu Glu Val Arg Asp Phe Gln Leu Arg Asp 290 295 300 Lys Tyr Met Phe Ala Thr Lys Val Val His Leu Leu Gly Ser Glu Gln 305 310 315 320 Gln Ser Ser Val Gln Leu Trp Val Ser Phe Gly Arg Lys Pro Met Arg 325 330 335 Ala Ala Gln Phe Val Thr Arg His Pro Ile Asn Glu Tyr Tyr Ile Ala 340 345 350 Asp Ala Ser Glu Asp Gln Val Phe Val Cys Val Ser His Ser Asn Asn 355 360 365 Arg Thr Asn Leu Tyr Ile Ser Glu Ala Glu Gly Leu Lys Phe Ser Leu 370 375 380 Ser Leu Glu Asn Val Leu Tyr Tyr Ser Pro Gly Gly Ala Gly Ser Asp 385 390 395 400 Thr Leu Val Arg Tyr Phe Ala Asn Glu Pro Phe Ala Asp Phe His Arg 405 410 415 Val Glu Gly Leu Gln Gly Val Tyr Ile Ala Thr Leu Ile Asn Gly Ser 420 425 430 Met Asn Glu Glu Asn Met Arg Ser Val Ile Thr Phe Asp Lys Gly Gly 435 440 445 Thr Trp Glu Phe Leu Gln Ala Pro Ala Phe Thr Gly Tyr Gly Glu Lys 450 455 460 Ile Asn Cys Glu Leu Ser Gln Gly Cys Ser Leu His Leu Ala Gln Arg 465 470 475 480 Leu Ser Gln Leu Leu Asn Leu Gln Leu Arg Arg Met Pro Ile Leu Ser 485 490 495 Lys Glu Ser Ala Pro Gly Leu Ile Ile Ala Thr Gly Ser Val Gly Lys 500 505 510 Asn Leu Ala Ser Lys Thr Asn Val Tyr Ile Ser Ser Ser Ala Gly Ala 515 520 525 Arg Trp Arg Glu Ala Leu Pro Gly Pro His Tyr Tyr Thr Trp Gly Asp 530 535 540 His Gly Gly Ile Ile Thr Ala Ile Ala Gin Gly Met Glu Thr Asn Glu 545 550 555 560 Leu Lys Tyr Ser Thr Asn Glu Gly Glu Thr Trp Lys Thr Phe Ile Phe 565 570 575 Ser Glu Lys Pro Val Phe Val Tyr Gly Leu Leu Thr Glu Pro Gly Glu 580 585 590 Lys Ser Thr Val Phe Thr Ile Phe Gly Ser Asn Lys Glu Asn Val His 595 600 605 Ser Trp Leu Ile Leu Gln Val Asn Ala Thr Asp Ala Leu Gly Val Pro 610 615 620 Cys Thr Glu Asn Asp Tyr Lys Leu Trp Ser Pro Ser Asp Glu Arg Gly 625 630 635 640 Asn Glu Cys Leu Leu Gly His Lys Thr Val Phe Lys Arg Arg Thr Pro 645 650 655 His Ala Thr Cys Phe Asn Gly Glu Asp Phe Asp Arg Pro Val Val Val 660 665 670 Ser Asn Cys Ser Cys Thr Arg Glu Asp Tyr Glu Cys Asp Phe Gly Phe 675 680 685 Lys Met Ser Glu Asp Leu Ser Leu Glu Val Cys Val Pro Asp Pro Glu 690 695 700 Phe Ser Gly Lys Ser Tyr Ser Pro Pro Val Pro Cys Pro Val Gly Ser 705 710 715 720 Thr Tyr Arg Arg Thr Arg Gly Tyr Arg Lys Ile Ser Gly Asp Thr Cys 725 730 735 Ser Gly Gly Asp Val Glu Ala Arg Leu Glu Gly Glu Leu Val Pro Cys 740 745 750 Pro Leu Ala Glu Glu Asn Glu Phe Ile Leu Tyr Ala Val Arg Lys Ser 755 760 765 Ile Tyr Arg Tyr Asp Leu Ala Ser Gly Ala Thr Glu Gln Leu Pro Leu 770 775 780 Thr Gly Leu Arg Ala Ala Val Ala Leu Asp Phe Asp Tyr Glu His Asn 785 790 795 800 Cys Leu Tyr Trp Ser Asp Leu Ala Leu Asp Val Ile Gln Arg Leu Cys 805 810 815 Leu Asn Gly Ser Thr Gly Gln Glu Val Ile Ile Asn Ser Gly Leu Glu 820 825 830 Thr Val Glu Ala Leu Ala Phe Glu Pro Leu Ser Gln Leu Leu Tyr Trp 835 840 845 Val Asp Ala Gly Phe Lys Lys Ile Glu Val Ala Asn Pro Asp Gly Asp 850 855 860 Phe Arg Leu Thr Ile Val Asn Ser Ser Val Leu Asp Arg Pro Arg Ala 865 870 875 880 Leu Val Leu Val Pro Gln Glu Gly Val Met Phe Trp Thr Asp Trp Gly 885 890 895 Asp Leu Lys Pro Gly Ile Tyr Arg Ser Asn Met Asp Gly Ser Ala Ala 900 905 910 Tyr His Leu Val Ser Glu Asp Val Lys Trp Pro Asn Gly Ile Ser Val 915 920 925 Asp Asp Gln Trp Ile Tyr Trp Thr Asp Ala Tyr Leu Glu Cys Ile Glu 930 935 940 Arg Ile Thr Phe Ser Gly Gln Gln Arg Ser Val Ile Leu Asp Asn Leu 945 950 955 960 Pro His Pro Tyr Ala Ile Ala Val Phe Lys Asn Glu Ile Tyr Trp Asp 965 970 975 Asp Trp Ser Gln Leu Ser Ile Phe Arg Ala Ser Lys Tyr Ser Gly Ser 980 985 990 Gln Met Glu Ile Leu Ala Asn Gln Leu Thr Gly Leu Met Asp Met Lys 995 1000 1005 Ile Phe Tyr Lys Gly Lys Asn Thr Gly Ser Asn Ala Cys Val Pro Arg 1010 1015 1020 Pro Cys Ser Leu Leu Cys Leu Pro Lys Ala Asn Asn Ser Arg Ser Cys 1025 1030 1035 1040 Arg Cys Pro Glu Asp Val Ser Ser Ser Val Leu Pro Ser Gly Asp Leu 1045 1050 1055 Met Cys Asp Cys Pro Gln Gly Tyr Gln Leu Lys Asn Asn Thr Cys Val 1060 1065 1070 Lys Gln Glu Asn Thr Cys Leu Arg Asn Gln Tyr Arg Cys Ser Asn Gly 1075 1080 1085 Asn Cys Ile Asn Ser Ile Trp Trp Cys Asp Phe Asp Asn Asp Cys Gly 1090 1095 1100 Asp Met Ser Asp Glu Arg Asn Cys Pro Thr Thr Ile Cys Asp Leu Asp 1105 1110 1115 1120 Thr Gln Phe Arg Cys Gln Glu Ser Gly Thr Cys Ile Pro Leu Ser Tyr 1125 1130 1135 Lys Cys Asp Leu Glu Asp Asp Cys Gly Asp Asn Ser Asp Glu Ser His 1140 1145 1150 Cys Glu Met His Gln Cys Arg Ser Asp Glu Tyr Asn Cys Ser Ser Gly 1155 1160 1165 Met Cys Ile Arg Ser Ser Trp Val Cys Asp Gly Asp Asn Asp Cys Arg 1170 1175 1180 Asp Trp Ser Asp Glu Ala Asn Cys Thr Ala Ile Tyr His Thr Cys Glu 1185 1190 1195 1200 Ala Ser Asn Phe Gln Cys Arg Asn Gly His Cys Ile Pro Gln Arg Trp 1205 1210 1215 Ala Cys Asp Gly Asp Thr Asp Cys Gln Asp Gly Ser Asp Glu Asp Pro 1220 1225 1230 Val Asn Cys Glu Lys Lys Cys Asn Gly Phe Arg Cys Pro Asn Gly Thr 1235 1240 1245 Cys Ile Pro Ser Ser Lys His Cys Asp Gly Leu Arg Asp Cys Ser Asp 1250 1255 1260 Gly Ser Asp Glu Gln His Cys Glu Pro Leu Cys Thr His Phe Met Asp 1265 1270 1275 1280 Phe Val Cys Lys Asn Arg Gln Gln Cys Leu Phe His Ser Met Val Cys 1285 1290 1295 Asp Gly Ile Ile Gln Cys Arg Asp Gly Ser Asp Glu Asp Ala Ala Phe 1300 1305 1310 Ala Gly Cys Ser Gln Asp Pro Glu Phe His Lys Val Cys Asp Glu Phe 1315 1320 1325 Gly Phe Gln Cys Gln Asn Gly Val Cys Ile Ser Leu Ile Trp Lys Cys 1330 1335 1340 Asp Gly Met Asp Asp Cys Gly Asp Tyr Ser Asp Glu Ala Asn Cys Glu 1345 1350 1355 1360 Asn Pro Thr Glu Ala Pro Asn Cys Ser Arg Tyr Phe Gln Phe Arg Cys 1365 1370 1375 Glu Asn Gly His Cys Ile Pro Asn Arg Trp Lys Cys Asp Arg Glu Asn 1380 1385 1390 Asp Cys Gly Asp Trp Ser Asp Glu Lys Asp Cys Gly Asp Ser His Ile 1395 1400 1405 Leu Pro Phe Ser Thr Pro Gly Pro Ser Thr Cys Leu Pro Asn Tyr Tyr 1410 1415 1420 Arg Cys Ser Ser Gly Thr Cys Val Met Asp Thr Trp Val Cys Asp Gly 1425 1430 1435 1440 Tyr Arg Asp Cys Ala Asp Gly Ser Asp Glu Glu Ala Cys Pro Leu Leu 1445 1450 1455 Ala Asn Val Thr Ala Ala Ser Thr Pro Thr Gln Leu Gly Arg Cys Asp 1460 1465 1470 Arg Phe Glu Phe Glu Cys His Gln Pro Lys Thr Cys Ile Pro Asn Trp 1475 1480 1485 Lys Arg Cys Asp Gly His Gln Asp Cys Gln Asp Gly Arg Asp Glu Ala 1490 1495 1500 Asn Cys Pro Thr His Ser Thr Leu Thr Cys Met Ser Arg Glu Phe Gln 1505 1510 1515 1520 Cys Glu Asp Gly Glu Ala Cys Ile Val Leu Ser Glu Arg Cys Asp Gly 1525 1530 1535 Phe Leu Asp Cys Ser Asp Glu Ser Asp Glu Lys Ala Cys Ser Asp Glu 1540 1545 1550 Leu Thr Val Tyr Lys Val Gln Asn Leu Gln Trp Thr Ala Asp Phe Ser 1555 1560 1565 Gly Asp Val Thr Leu Thr Trp Met Arg Pro Lys Lys Met Pro Ser Ala 1570 1575 1580 Ser Cys Val Tyr Asn Val Tyr Tyr Arg Val Val Gly Glu Ser Ile Trp 1585 1590 1595 1600 Lys Thr Leu Glu Thr His Ser Asn Lys Thr Asn Thr Val Leu Lys Val 1605 1610 1615 Leu Lys Pro Asp Thr Thr Tyr Gln Val Lys Val Gln Val Gln Cys Leu 1620 1625 1630 Ser Lys Ala His Asn Thr Asn Asp Phe Val Thr Leu Arg Thr Pro Glu 1635 1640 1645 Gly Leu Pro Asp Ala Pro Arg Asn Leu Gln Leu Ser Leu Pro Arg Glu 1650 1655 1660 Ala Glu Gly Val Ile Val Gly His Trp Ala Pro Pro Ile His Thr His 1665 1670 1675 1680 Gly Leu Ile Arg Glu Tyr Ile Val Glu Tyr Ser Arg Ser Gly Ser Lys 1685 1690 1695 Met Trp Ala Ser Gln Arg Ala Ala Ser Asn Phe Thr Glu Ile Lys Asn 1700 1705 1710 Leu Leu Val Asn Thr Leu Tyr Thr Val Arg Val Ala Ala Val Thr Ser 1715 1720 1725 Arg Gly Ile Gly Asn Trp Ser Asp Ser Lys Ser Ile Thr Thr Ile Lys 1730 1735 1740 Gly Lys Val Ile Pro Pro Asp Ile His Ile Asp Ser Tyr Gly Glu 1745 1750 1755 1760 Asn Tyr Leu Ser Phe Thr Leu Thr Met Glu Ser Asp Ile Lys Val Asn 1765 1770 1775 Gly Tyr Val Val Asn Leu Phe Trp Ala Phe Asp Thr His Lys Gln Glu 1780 1785 1790 Arg Arg Thr Leu Asn Phe Arg Gly Ser Ile Leu Ser His Lys Val Gly 1795 1800 1805 Asn Leu Thr Ala His Thr Ser Tyr Glu Ile Ser Ala Trp Ala Lys Thr 1810 1815 1820 Asp Leu Gly Asp Ser Pro Leu Ala Phe Glu His Val Met Thr Arg Gly 1825 1830 1835 1840 Val Arg Pro Pro Ala Pro Ser Leu Lys Ala Lys Ala Ile Asn Gln Thr 1845 1850 1855 Ala Val Glu Cys Thr Trp Thr Gly Pro Arg Asn Val Val Tyr Gly Ile 1860 1865 1870 Phe Tyr Ala Thr Ser Phe Leu Asp Leu Tyr Arg Asn Pro Lys Ser Leu 1875 1880 1885 Thr Thr Ser Leu His Asn Lys Thr Val Ile Val Ser Lys Asp Glu Gln 1890 1895 1900 Tyr Leu Phe Leu Val Arg Val Val Val Pro Tyr Gln Gly Pro Ser Ser 1905 1910 1915 1920 Asp Tyr Val Val Val Lys Met Ile Pro Asp Ser Arg Leu Pro Pro Arg 1925 1930 1935 His Leu His Val Val His Thr Gly Lys Thr Ser Val Val Ile Lys Trp 1940 1945 1950 Glu Ser Pro Tyr Asp Ser Pro Asp Gln Asp Leu Leu Tyr Ala Val Ala 1955 1960 1965 Val Lys Asp Leu Ile Arg Lys Thr Asp Arg Ser Tyr Lys Val Lys Ser 1970 1975 1980 Arg Asn Ser Thr Val Glu Tyr Thr Leu Asn Lys Leu Glu Pro Gly Gly 1985 1990 1995 2000 Lys Tyr His Ile Ile Val Gln Leu Gly Asn Met Ser Lys Asp Ser Ser 2005 2010 2015 Ile Lys Ile Thr Thr Val Ser Leu Ser Ala Pro Asp Ala Leu Lys Ile 2020 2025 2030 Ile Thr Glu Asn Asp His Val Leu Leu Phe Trp Lys Ser Leu Ala Leu 2035 2040 2045 Lys Glu Lys His Phe Asn Glu Ser Arg Gly Tyr Glu Ile His Met Phe 2050 2055 2060 Asp Ser Ala Met Asn Ile Thr Ala Tyr Leu Gly Asn Thr Thr Asp Asn 2065 2070 2075 2080 Phe Phe Lys Ile Ser Asn Leu Lys Met Gly His Asn Tyr Thr Phe Thr 2085 2090 2095 Val Gln Ala Arg Cys Leu Phe Gly Asn Gln Ile Cys Gly Glu Pro Ala 2100 2105 2110 Ile Leu Leu Tyr Asp Glu Leu Gly Ser Gly Ala Asp Ala Ser Ala Thr 2115 2120 2125 Gln Ala Ala Arg Ser Thr Asp Val Ala Ala Val Val Val Pro Ile Leu 2130 2135 2140 Phe Leu Ile Leu Leu Ser Leu Gly Val Gly Phe Ala Ile Leu Tyr Thr 2145 2150 2155 2160 Lys His Arg Arg Leu Gln Ser Ser Phe Thr Ala Phe Ala Asn Ser His 2165 2170 2175 Tyr Ser Ser Arg Leu Gly Ser Ala Ile Phe Ser Ser Gly Asp Asp Leu 2180 2185 2190 Gly Glu Asp Asp Glu Asp Ala Pro Met Ile Thr Gly Phe Ser Asp Asp 2195 2200 2205 Val Pro Met Val Ile Ala 2210 <210> 39 <211> 784 <212> PRT <213> Homo sapiens <400> 39 Met Ser Asp Gln Lys Lys Glu Glu Glu Glu Glu Ala Ala Ala Ala Ala 1 5 10 15 Ala Met Ala Thr Glu Gly Gly Lys Thr Ser Glu Pro Glu Asn Asn Asn 20 25 30 Lys Lys Pro Lys Thr Ser Gly Ser Gln Asp Ser Gln Pro Ser Pro Leu 35 40 45 Ala Leu Leu Ala Ala Thr Cys Ser Lys Ile Gly Thr Pro Gly Glu Asn 50 55 60 Gln Ala Thr Gly Gln Gln Gln Ile Ile Ile Asp Pro Ser Gln Gly Leu 65 70 75 80 Val Gln Leu Gln Asn Gln Pro Gln Gln Leu Glu Leu Val Thr Thr Gln 85 90 95 Leu Ala Gly Asn Ala Trp Gln Leu Val Ala Ser Thr Pro Pro Ala Ser 100 105 110 Lys Glu Asn Asn Val Ser Gln Pro Ala Ser Ser Ser Ser Ser Ser Ser Ser 115 120 125 Ser Ser Asn Asn Gly Ser Ala Ser Pro Thr Lys Thr Lys Ser Gly Asn 130 135 140 Ser Ser Thr Pro Gly Gln Phe Gln Val Ile Gln Val Gln Asn Pro Ser 145 150 155 160 Gly Ser Val Gln Tyr Gln Val Ile Pro Gln Leu Gln Thr Val Glu Gly 165 170 175 Gln Gln Ile Gln Ile Asn Pro Thr Ser Ser Ser Ser Leu Gln Asp Leu 180 185 190 Gln Gly Gln Ile Gln Leu Ile Ser Ala Gly Asn Asn Gln Ala Ile Leu 195 200 205 Thr Ala Ala Asn Arg Thr Ala Ser Gly Asn Ile Leu Ala Gln Asn Leu 210 215 220 Ala Asn Gln Thr Val Pro Val Gln Ile Arg Pro Gly Val Ser Ile Pro 225 230 235 240 Leu Gln Leu Gln Thr Leu Pro Gly Thr Gln Ala Gln Val Val Thr Thr 245 250 255 Leu Pro Ile Asn Ile Gly Gly Val Thr Leu Ala Leu Pro Val Ile Asn 260 265 270 Asn Val Ala Ala Gly Gly Gly Thr Gly Gln Val Gly Gln Pro Ala Ala 275 280 285 Thr Ala Asp Ser Gly Thr Ser Asn Gly Asn Gln Leu Val Ser Thr Pro 290 295 300 Thr Asn Thr Thr Thr Ser Ala Ser Thr Met Pro Glu Ser Pro Ser Ser Ser 305 310 315 320 Ser Thr Thr Cys Thr Thr Thr Ala Ser Thr Ser Leu Thr Ser Ser Asp 325 330 335 Thr Leu Val Ser Ser Ala Asp Thr Gly Gln Tyr Ala Ser Thr Ser Ala 340 345 350 Ser Ser Ser Glu Arg Thr Ile Glu Glu Ser Gln Thr Pro Ala Ala Thr 355 360 365 Glu Ser Glu Ala Gln Ser Ser Ser Gln Leu Gln Pro Asn Gly Met Gln 370 375 380 Asn Ala Gln Asp Gln Ser Asn Ser Leu Gln Gln Val Gln Ile Val Gly 385 390 395 400 Gln Pro Ile Leu Gln Gln Ile Gln Ile Gln Gln Pro Gln Gln Gln Ile 405 410 415 Ile Gln Ala Ile Pro Pro Gln Ser Phe Gln Leu Gln Ser Gly Gln Thr 420 425 430 Ile Gln Thr Ile Gln Gln Gln Pro Leu Gln Asn Val Gln Leu Gln Ala 435 440 445 Val Asn Pro Thr Gln Val Leu Ile Arg Ala Pro Thr Leu Thr Pro Ser 450 455 460 Gly Gln Ile Ser Trp Gln Thr Val Gln Val Gln Asn Ile Gln Ser Leu 465 470 475 480 Ser Asn Leu Gln Val Gln Asn Ala Gly Leu Ser Gln Gln Leu Thr Ile 485 490 495 Thr Pro Val Ser Ser Ser Gly Gly Thr Thr Leu Ala Gln Ile Ala Pro 500 505 510 Val Ala Val Ala Gly Ala Pro Ile Thr Leu Asn Thr Ala Gln Leu Ala 515 520 525 Ser Val Pro Asn Leu Gln Thr Val Ser Val Ala Asn Leu Gly Ala Ala 530 535 540 Gly Val Gln Val Gln Gly Val Pro Val Thr Ile Thr Ser Val Ala Gly 545 550 555 560 Gln Gln Gln Gly Gln Asp Gly Val Lys Val Gln Gln Ala Thr Ile Ala 565 570 575 Pro Val Thr Val Ala Val Gly Gly Ile Ala Asn Ala Thr Ile Gly Ala 580 585 590 Val Ser Pro Asp Gln Leu Thr Gln Val His Leu Gln Gln Gly Gln Gln 595 600 605 Thr Ser Asp Gln Glu Val Gln Pro Gly Lys Arg Leu Arg Arg Val Ala 610 615 620 Cys Ser Cys Pro Asn Cys Arg Glu Gly Glu Gly Arg Gly Ser Asn Glu 625 630 635 640 Pro Gly Lys Lys Lys Gln His Ile Cys His Ile Glu Gly Cys Gly Lys 645 650 655 Val Tyr Gly Lys Thr Ser His Leu Arg Ala His Leu Arg Trp His Thr 660 665 670 Gly Glu Arg Pro Phe Ile Cys Asn Trp Met Phe Cys Gly Lys Arg Phe 675 680 685 Thr Arg Ser Asp Glu Leu Gln Arg His Arg Arg Thr His Thr Gly Glu 690 695 700 Lys Arg Phe Glu Cys Pro Glu Cys Ser Lys Arg Phe Met Arg Ser Asp 705 710 715 720 His Leu Ser Lys His Val Lys Thr His Gln Asn Lys Lys Gly Gly Gly 725 730 735 Thr Ala Leu Ala Ile Val Thr Ser Gly Glu Leu Asp Ser Ser Val Thr 740 745 750 Glu Val Leu Gly Ser Pro Arg Ile Val Thr Val Ala Ala Ile Ser Gln 755 760 765 Asp Ser Asn Pro Ala Thr Pro Asn Val Ser Thr Asn Met Glu Glu Phe 770 775 780 <210> 40 <211> 1266 <212> PRT <213> Homo sapiens <400> 40 Met Trp Val Asn Pro Glu Glu Val Leu Leu Ala Asn Ala Leu Trp Ile 1 5 10 15 Thr Glu Arg Ala Asn Pro Tyr Phe Ile Leu Gln Arg Arg Lys Gly His 20 25 30 Ala Gly Asp Gly Gly Gly Gly Gly Gly Leu Ala Gly Leu Leu Val Gly 35 40 45 Thr Leu Asp Val Val Leu Asp Ser Ser Ala Arg Val Ala Pro Tyr Arg 50 55 60 Ile Leu Tyr Gln Thr Pro Asp Ser Leu Val Tyr Trp Thr Ile Ala Cys 65 70 75 80 Gly Gly Ser Arg Lys Glu Ile Thr Glu His Trp Glu Trp Leu Glu Gln 85 90 95 Asn Leu Leu Gln Thr Leu Ser Ile Phe Glu Asn Glu Asn Asp Ile Thr 100 105 110 Thr Phe Val Arg Gly Lys Ile Gln Gly Ile Ile Ala Glu Tyr Asn Lys 115 120 125 Ile Asn Asp Val Lys Glu Asp Asp Asp Thr Glu Lys Phe Lys Glu Ala 130 135 140 Ile Val Lys Phe His Arg Leu Phe Gly Met Pro Glu Glu Glu Lys Leu 145 150 155 160 Val Asn Tyr Tyr Ser Cys Ser Tyr Trp Lys Gly Lys Val Pro Arg Gln 165 170 175 Gly Trp Met Tyr Leu Ser Ile Asn His Leu Cys Phe Tyr Ser Phe Leu 180 185 190 Met Gly Arg Glu Ala Lys Leu Val Ile Arg Trp Val Asp Ile Thr Gln 195 200 205 Leu Glu Lys Asn Ala Thr Leu Leu Leu Pro Asp Val Ile Lys Val Ser 210 215 220 Thr Arg Ser Ser Glu His Phe Phe Ser Val Phe Leu Asn Ile Asn Glu 225 230 235 240 Thr Phe Lys Leu Met Glu Gln Leu Ala Asn Ile Ala Met Arg Gln Leu 245 250 255 Leu Asp Asn Glu Gly Phe Glu Gln Asp Arg Ser Leu Pro Lys Leu Lys 260 265 270 Arg Lys Ser Pro Lys Lys Val Ser Ala Leu Lys Arg Asp Leu Asp Ala 275 280 285 Arg Ala Lys Ser Glu Arg Tyr Arg Ala Leu Phe Arg Leu Pro Lys Asp 290 295 300 Glu Lys Leu Asp Gly His Thr Asp Cys Thr Leu Trp Thr Pro Phe Asn 305 310 315 320 Lys Met His Ile Leu Gly Gln Met Phe Val Ser Thr Asn Tyr Ile Cys 325 330 335 Phe Thr Ser Lys Glu Glu Asn Leu Cys Ser Leu Ile Ile Pro Leu Arg 340 345 350 Glu Val Thr Ile Val Glu Lys Ala Asp Ser Ser Ser Val Leu Pro Ser 355 360 365 Pro Leu Ser Ile Ser Thr Arg Asn Arg Met Thr Phe Leu Phe Ala Asn 370 375 380 Leu Lys Asp Arg Asp Phe Leu Val Gln Arg Ile Ser Asp Phe Leu Gln 385 390 395 400 Gln Thr Thr Ser Lys Ile Tyr Ser Asp Lys Glu Phe Ala Gly Ser Tyr 405 410 415 Asn Ser Ser Asp Asp Glu Val Tyr Ser Arg Pro Ser Ser Leu Val Ser 420 425 430 Ser Ser Pro Gln Arg Ser Thr Ser Ser Asp Ala Asp Gly Glu Arg Gln 435 440 445 Phe Asn Leu Asn Gly Asn Ser Val Pro Thr Ala Thr Gln Thr Leu Met 450 455 460 Thr Met Tyr Arg Arg Arg Ser Pro Glu Glu Phe Asn Pro Lys Leu Ala 465 470 475 480 Lys Glu Phe Leu Lys Glu Gln Ala Trp Lys Ile His Phe Ala Glu Tyr 485 490 495 Gly Gln Gly Ile Cys Met Tyr Arg Thr Glu Lys Thr Arg Glu Leu Val 500 505 510 Leu Lys Gly Ile Pro Glu Ser Met Arg Gly Glu Leu Trp Leu Leu Leu 515 520 525 Ser Gly Ala Ile Asn Glu Lys Ala Thr His Pro Gly Tyr Tyr Glu Asp 530 535 540 Leu Val Glu Lys Ser Met Gly Lys Tyr Asn Leu Ala Thr Glu Glu Ile 545 550 555 560 Glu Arg Asp Leu His Arg Ser Leu Pro Glu His Pro Ala Phe Gln Asn 565 570 575 Glu Met Gly Ile Ala Ala Leu Arg Arg Val Leu Thr Ala Tyr Ala Phe 580 585 590 Arg Asn Pro Asn Ile Gly Tyr Cys Gln Ala Met Asn Ile Val Thr Ser 595 600 605 Val Leu Leu Leu Tyr Ala Lys Glu Glu Glu Ala Phe Trp Leu Leu Val 610 615 620 Ala Leu Cys Glu Arg Met Leu Pro Asp Tyr Tyr Asn Thr Arg Val Val 625 630 635 640 Gly Ala Leu Val Asp Gln Gly Val Phe Glu Glu Leu Ala Arg Asp Tyr 645 650 655 Val Pro Gln Leu Tyr Asp Cys Met Gln Asp Leu Gly Val Ile Ser Thr 660 665 670 Ile Ser Leu Ser Trp Phe Leu Thr Leu Phe Leu Ser Val Met Pro Phe 675 680 685 Glu Ser Ala Val Val Val Val Val Asp Cys Phe Phe Tyr Glu Gly Ile Lys 690 695 700 Val Ile Phe Gln Leu Ala Leu Ala Val Leu Asp Ala Asn Val Asp Lys 705 710 715 720 Leu Leu Asn Cys Lys Asp Asp Gly Glu Ala Met Thr Val Leu Gly Arg 725 730 735 Tyr Leu Asp Ser Val Thr Asn Lys Asp Ser Thr Leu Pro Pro Ile Pro 740 745 750 His Leu His Ser Leu Leu Ser Asp Asp Val Glu Pro Tyr Pro Glu Val 755 760 765 Asp Ile Phe Arg Leu Ile Arg Thr Ser Tyr Glu Lys Phe Gly Thr Ile 770 775 780 Arg Ala Asp Leu Ile Glu Gln Met Arg Phe Lys Gln Arg Leu Lys Val 785 790 795 800 Ile Gln Thr Leu Glu Asp Thr Thr Lys Arg Asn Val Val Arg Thr Ile 805 810 815 Val Thr Glu Thr Ser Phe Thr Ile Asp Glu Leu Glu Glu Leu Tyr Ala 820 825 830 Leu Phe Lys Ala Glu His Leu Thr Ser Cys Tyr Trp Gly Gly Ser Ser 835 840 845 Asn Ala Leu Asp Arg His Asp Pro Ser Leu Pro Tyr Leu Glu Gln Tyr 850 855 860 Arg Ile Asp Phe Glu Gln Phe Lys Gly Met Phe Ala Leu Leu Phe Pro 865 870 875 880 Trp Ala Cys Gly Thr His Ser Asp Val Leu Ala Ser Arg Leu Phe Gln 885 890 895 Leu Leu Asp Glu Asn Gly Asp Ser Leu Ile Asn Phe Arg Glu Phe Val 900 905 910 Ser Gly Leu Ser Ala Ala Cys His Gly Asp Leu Thr Glu Lys Leu Lys 915 920 925 Leu Leu Tyr Lys Met His Val Leu Pro Glu Pro Ser Ser Asp Gln Asp 930 935 940 Glu Pro Asp Ser Ala Phe Glu Ala Thr Gln Tyr Phe Phe Glu Asp Ile 945 950 955 960 Thr Pro Glu Cys Thr His Val Val Gly Leu Asp Ser Arg Ser Lys Gln 965 970 975 Gly Ala Asp Asp Gly Phe Val Thr Val Ser Leu Lys Pro Asp Lys Gly 980 985 990 Lys Arg Ala Asn Ser Gln Glu Asn Arg Asn Tyr Leu Arg Leu Trp Thr 995 1000 1005 Pro Glu Asn Lys Ser Lys Ser Lys Asn Ala Lys Asp Leu Pro Lys Leu 1010 1015 1020 Asn Gln Gly Gln Phe Ile Glu Leu Cys Lys Thr Met Tyr Asn Met Phe 1025 1030 1035 1040 Ser Glu Asp Pro Asn Glu Gln Glu Leu Tyr His Ala Thr Ala Ala Val 1045 1050 1055 Thr Ser Leu Leu Leu Glu Ile Gly Glu Val Gly Lys Leu Phe Val Ala 1060 1065 1070 Gln Pro Ala Lys Glu Gly Gly Ser Gly Gly Ser Gly Pro Ser Cys His 1075 1080 1085 Gln Gly Ile Pro Gly Val Leu Phe Pro Lys Lys Gly Pro Gly Gln Pro 1090 1095 1100 Tyr Val Val Glu Ser Val Glu Pro Leu Pro Ala Ser Leu Ala Pro Asp 1105 1110 1115 1120 Ser Glu Glu His Ser Leu Gly Gly Gln Met Glu Asp Ile Lys Leu Glu 1125 1130 1135 Asp Ser Ser Pro Arg Asp Asn Gly Ala Cys Ser Ser Met Leu Ile Ser 1140 1145 1150 Asp Asp Asp Thr Lys Asp Asp Ser Ser Met Ser Ser Tyr Ser Val Leu 1155 1160 1165 Ser Ala Gly Ser His Glu Glu Asp Lys Leu His Cys Glu Asp Ile Gly 1170 1175 1180 Glu Asp Thr Val Leu Val Arg Ser Gly Gin Gly Thr Ala Ala Leu Pro 1185 1190 1195 1200 Arg Ser Thr Ser Leu Asp Arg Asp Trp Ala Ile Thr Phe Glu Gln Phe 1205 1210 1215 Leu Ala Ser Leu Leu Thr Glu Pro Ala Leu Val Lys Tyr Phe Asp Lys 1220 1225 1230 Pro Val Cys Met Met Ala Arg Ile Thr Ser Ala Lys Asn Ile Arg Met 1235 1240 1245 Met Gly Lys Pro Leu Thr Ser Ala Ser Asp Tyr Glu Ile Ser Ala Met 1250 1255 1260 Ser Gly 1265 <210> 41 <211> 1124 <212> PRT <213> Homo sapiens <400> 41 Met Asp Ser Leu Ala Ser Leu Val Leu Cys Gly Val Ser Leu Leu Leu 1 5 10 15 Ser Gly Thr Val Glu Gly Ala Met Asp Leu Ile Leu Ile Asn Ser Leu 20 25 30 Pro Leu Val Ser Asp Ala Glu Thr Ser Leu Thr Cys Ile Ala Ser Gly 35 40 45 Trp Arg Pro His Glu Pro Ile Thr Ile Gly Arg Asp Phe Glu Ala Leu 50 55 60 Met Asn Gln His Gln Asp Pro Leu Glu Val Thr Gln Asp Val Thr Arg 65 70 75 80 Glu Trp Ala Lys Lys Val Val Trp Lys Arg Glu Lys Ala Ser Lys Ile 85 90 95 Asn Gly Ala Tyr Phe Cys Glu Gly Arg Val Arg Gly Glu Ala Ile Arg 100 105 110 Ile Arg Thr Met Lys Met Arg Gln Gln Ala Ser Phe Leu Pro Ala Thr 115 120 125 Leu Thr Met Thr Val Asp Lys Gly Asp Asn Val Asn Ile Ser Phe Lys 130 135 140 Lys Val Leu Ile Lys Glu Glu Asp Ala Val Ile Tyr Lys Asn Gly Ser 145 150 155 160 Phe Ile His Ser Val Pro Arg His Glu Val Pro Asp Ile Leu Glu Val 165 170 175 His Leu Pro His Ala Gln Pro Gln Asp Ala Gly Val Tyr Ser Ala Arg 180 185 190 Tyr Ile Gly Gly Asn Leu Phe Thr Ser Ala Phe Thr Arg Leu Ile Val 195 200 205 Arg Arg Cys Glu Ala Gln Lys Trp Gly Pro Glu Cys Asn His Leu Cys 210 215 220 Thr Ala Cys Met Asn Asn Gly Val Cys His Glu Asp Thr Gly Glu Cys 225 230 235 240 Ile Cys Pro Pro Gly Phe Met Gly Arg Thr Cys Glu Lys Ala Cys Glu 245 250 255 Leu His Thr Phe Gly Arg Thr Cys Lys Glu Arg Cys Ser Gly Gln Glu 260 265 270 Gly Cys Lys Ser Tyr Val Phe Cys Leu Pro Asp Pro Tyr Gly Cys Ser 275 280 285 Cys Ala Thr Gly Trp Lys Gly Leu Gln Cys Asn Glu Ala Cys His Pro 290 295 300 Gly Phe Tyr Gly Pro Asp Cys Lys Leu Arg Cys Ser Cys Asn Asn Gly 305 310 315 320 Glu Met Cys Asp Arg Phe Gln Gly Cys Leu Cys Ser Pro Gly Trp Gln 325 330 335 Gly Leu Gln Cys Glu Arg Glu Gly Ile Pro Arg Met Thr Pro Lys Ile 340 345 350 Val Asp Leu Pro Asp His Ile Glu Val Asn Ser Gly Lys Phe Asn Pro 355 360 365 Ile Cys Lys Ala Ser Gly Trp Pro Leu Pro Thr Asn Glu Glu Met Thr 370 375 380 Leu Val Lys Pro Asp Gly Thr Val Leu His Pro Lys Asp Phe Asn His 385 390 395 400 Thr Asp His Phe Ser Val Ala Ile Phe Thr Ile His Arg Ile Leu Pro 405 410 415 Pro Asp Ser Gly Val Trp Val Cys Ser Val Asn Thr Val Ala Gly Met 420 425 430 Val Glu Lys Pro Phe Asn Ile Ser Val Lys Val Leu Pro Lys Pro Leu 435 440 445 Asn Ala Pro Asn Val Ile Asp Thr Gly His Asn Phe Ala Val Ile Asn 450 455 460 Ile Ser Ser Glu Pro Tyr Phe Gly Asp Gly Pro Ile Lys Ser Lys Lys 465 470 475 480 Leu Leu Tyr Lys Pro Val Asn His Tyr Glu Ala Trp Gln His Ile Gln 485 490 495 Val Thr Asn Glu Ile Val Thr Leu Asn Tyr Leu Glu Pro Arg Thr Glu 500 505 510 Tyr Glu Leu Cys Val Gln Leu Val Arg Arg Gly Glu Gly Gly Glu Gly 515 520 525 His Pro Gly Pro Val Arg Arg Phe Thr Thr Ala Ser Ile Gly Leu Pro 530 535 540 Pro Pro Arg Gly Leu Asn Leu Leu Pro Lys Ser Gln Thr Thr Leu Asn 545 550 555 560 Leu Thr Trp Gln Pro Ile Phe Pro Ser Ser Glu Asp Asp Phe Tyr Val 565 570 575 Glu Val Glu Arg Arg Ser Val Gln Lys Ser Asp Gln Gln Asn Ile Lys 580 585 590 Val Pro Gly Asn Leu Thr Ser Val Leu Leu Asn Asn Leu His Pro Arg 595 600 605 Glu Gln Tyr Val Val Arg Ala Arg Val Asn Thr Lys Ala Gln Gly Glu 610 615 620 Trp Ser Glu Asp Leu Thr Ala Trp Thr Leu Ser Asp Ile Leu Pro Pro 625 630 635 640 Gln Pro Glu Asn Ile Lys Ile Ser Asn Ile Thr His Ser Ser Ala Val 645 650 655 Ile Ser Trp Thr Ile Leu Asp Gly Tyr Ser Ile Ser Ser Ile Thr Ile 660 665 670 Arg Tyr Lys Val Gln Gly Lys Asn Glu Asp Gln His Val Asp Val Lys 675 680 685 Ile Lys Asn Ala Thr Ile Thr Gln Tyr Gln Leu Lys Gly Leu Glu Pro 690 695 700 Glu Thr Ala Tyr Gln Val Asp Ile Phe Ala Glu Asn Asn Ile Gly Ser 705 710 715 720 Ser Asn Pro Ala Phe Ser His Glu Leu Val Thr Leu Pro Glu Ser Gln 725 730 735 Ala Pro Ala Asp Leu Gly Gly Gly Lys Met Leu Leu Ile Ala Ile Leu 740 745 750 Gly Ser Ala Gly Met Thr Cys Leu Thr Val Leu Leu Ala Phe Leu Ile 755 760 765 Ile Leu Gln Leu Lys Arg Ala Asn Val Gln Arg Arg Met Ala Gln Ala 770 775 780 Phe Gln Asn Val Arg Glu Glu Pro Ala Val Gln Phe Asn Ser Gly Thr 785 790 795 800 Leu Ala Leu Asn Arg Lys Val Lys Asn Asn Pro Asp Pro Thr Ile Tyr 805 810 815 Pro Val Leu Asp Trp Asn Asp Ile Lys Phe Gln Asp Val Ile Gly Glu 820 825 830 Gly Asn Phe Gly Gln Val Leu Lys Ala Arg Ile Lys Lys Asp Gly Leu 835 840 845 Arg Met Asp Ala Ala Ile Lys Arg Met Lys Glu Tyr Ala Ser Lys Asp 850 855 860 Asp His Arg Asp Phe Ala Gly Glu Leu Glu Val Leu Cys Lys Leu Gly 865 870 875 880 His His Pro Asn Ile Ile Asn Leu Leu Gly Ala Cys Glu His Arg Gly 885 890 895 Tyr Leu Tyr Leu Ala Ile Glu Tyr Ala Pro His Gly Asn Leu Leu Asp 900 905 910 Phe Leu Arg Lys Ser Arg Val Leu Glu Thr Asp Pro Ala Phe Ala Ile 915 920 925 Ala Asn Ser Thr Ala Ser Thr Leu Ser Ser Gln Gln Leu Leu His Phe 930 935 940 Ala Ala Asp Val Ala Arg Gly Met Asp Tyr Leu Ser Gln Lys Gln Phe 945 950 955 960 Ile His Arg Asp Leu Ala Ala Arg Asn Ile Leu Val Gly Glu Asn Tyr 965 970 975 Val Ala Lys Ile Ala Asp Phe Gly Leu Ser Arg Gly Gln Glu Val Tyr 980 985 990 Val Lys Lys Thr Met Gly Arg Leu Pro Val Arg Trp Met Ala Ile Glu 995 1000 1005 Ser Leu Asn Tyr Ser Val Tyr Thr Thr Asn Ser Asp Val Trp Ser Tyr 1010 1015 1020 Gly Val Leu Leu Trp Glu Ile Val Ser Leu Gly Gly Thr Pro Tyr Cys 1025 1030 1035 1040 Gly Met Thr Cys Ala Glu Leu Tyr Glu Lys Leu Pro Gln Gly Tyr Arg 1045 1050 1055 Leu Glu Lys Pro Leu Asn Cys Asp Asp Glu Val Tyr Asp Leu Met Arg 1060 1065 1070 Gln Cys Trp Arg Glu Lys Pro Tyr Glu Arg Pro Ser Phe Ala Gln Ile 1075 1080 1085 Leu Val Ser Leu Asn Arg Met Leu Glu Glu Arg Lys Thr Tyr Val Asn 1090 1095 1100 Thr Thr Leu Tyr Glu Lys Phe Thr Tyr Ala Gly Ile Asp Cys Ser Ala 1105 1110 1115 1120 Glu Glu Ala Ala <210> 42 <211> 760 <212> PRT <213> Homo sapiens <400> 42 Met Ser Pro Lys Lys Val Gln Ile Lys Val Glu Glu Lys Glu Asp Glu 1 5 10 15 Thr Glu Glu Ser Ser Ser Ser Glu Glu Glu Glu Glu Val Glu Asp Lys Leu 20 25 30 Pro Arg Arg Glu Ser Leu Arg Pro Lys Arg Lys Arg Thr Arg Asp Val 35 40 45 Ile Asn Glu Asp Asp Pro Glu Pro Glu Pro Glu Asp Glu Glu Thr Arg 50 55 60 Lys Ala Arg Glu Lys Glu Arg Arg Arg Arg Leu Lys Arg Gly Ala Glu 65 70 75 80 Glu Glu Glu Ile Asp Glu Glu Glu Leu Glu Arg Leu Lys Ala Glu Leu 85 90 95 Asp Glu Lys Arg Gln Ile Ile Ala Thr Val Lys Cys Lys Pro Trp Lys 100 105 110 Met Glu Lys Lys Ile Glu Val Leu Lys Glu Ala Lys Lys Phe Val Ser 115 120 125 Glu Asn Glu Gly Ala Leu Gly Lys Gly Lys Gly Lys Arg Trp Phe Ala 130 135 140 Phe Lys Met Met Met Ala Lys Lys Trp Ala Lys Phe Leu Arg Asp Phe 145 150 155 160 Glu Asn Phe Lys Ala Ala Cys Val Pro Trp Glu Asn Lys Ile Lys Ala 165 170 175 Ile Glu Ser Gln Phe Gly Ser Ser Val Ala Ser Tyr Phe Leu Phe Leu 180 185 190 Arg Trp Met Tyr Gly Val Asn Met Val Leu Phe Ile Leu Thr Phe Ser 195 200 205 Leu Ile Met Leu Pro Glu Tyr Leu Trp Gly Leu Pro Tyr Gly Ser Leu 210 215 220 Pro Arg Lys Thr Val Pro Arg Ala Glu Glu Ala Ser Ala Ala Asn Phe 225 230 235 240 Gly Val Leu Tyr Asp Phe Asn Gly Leu Ala Gln Tyr Ser Val Leu Phe 245 250 255 Tyr Gly Tyr Tyr Asp Asn Lys Arg Thr Ile Gly Trp Met Asn Phe Arg 260 265 270 Leu Pro Leu Ser Tyr Phe Leu Val Gly Ile Met Cys Ile Gly Tyr Ser 275 280 285 Phe Leu Val Val Leu Lys Ala Met Thr Lys Asn Ile Gly Asp Asp Gly 290 295 300 Gly Gly Asp Asp Asn Thr Phe Asn Phe Ser Trp Lys Val Phe Thr Ser 305 310 315 320 Trp Asp Tyr Leu Ile Gly Asn Pro Glu Thr Ala Asp Asn Lys Phe Asn 325 330 335 Ser Ile Thr Met Asn Phe Lys Glu Ala Ile Thr Glu Glu Lys Ala Ala 340 345 350 Gln Val Glu Glu Asn Val His Leu Ile Arg Phe Leu Arg Phe Leu Ala 355 360 365 Asn Phe Phe Val Phe Leu Thr Leu Gly Gly Ser Gly Tyr Leu Ile Phe 370 375 380 Trp Ala Val Lys Arg Ser Gln Glu Phe Ala Gln Gln Asp Pro Asp Thr 385 390 395 400 Leu Gly Trp Trp Glu Lys Asn Glu Met Asn Met Val Met Ser Leu Leu 405 410 415 Gly Met Phe Cys Pro Thr Leu Phe Asp Leu Phe Ala Glu Leu Glu Asp 420 425 430 Tyr His Pro Leu Ile Ala Leu Lys Trp Leu Leu Gly Arg Ile Phe Ala 435 440 445 Leu Leu Leu Gly Asn Leu Tyr Val Phe Ile Leu Ala Leu Met Asp Glu 450 455 460 Ile Asn Asn Lys Ile Glu Glu Glu Lys Leu Val Lys Ala Asn Ile Thr 465 470 475 480 Leu Trp Glu Ala Asn Met Ile Lys Ala Tyr Asn Ala Ser Phe Ser Glu 485 490 495 Asn Ser Thr Gly Pro Pro Phe Phe Val His Pro Ala Asp Val Pro Arg 500 505 510 Gly Pro Cys Trp Glu Thr Met Val Gly Gin Glu Phe Val Arg Leu Thr 515 520 525 Val Ser Asp Val Leu Thr Thr Tyr Val Thr Ile Leu Ile Gly Asp Phe 530 535 540 Leu Arg Ala Cys Phe Val Arg Phe Cys Asn Tyr Cys Trp Cys Trp Asp 545 550 555 560 Leu Glu Tyr Gly Tyr Pro Ser Tyr Thr Glu Phe Asp Ile Ser Gly Asn 565 570 575 Val Leu Ala Leu Ile Phe Asn Gln Gly Met Ile Trp Met Gly Ser Phe 580 585 590 Phe Ala Pro Ser Leu Pro Gly Ile Asn Ile Leu Arg Leu His Thr Ser 595 600 605 Met Tyr Phe Gln Cys Trp Ala Val Met Cys Cys Asn Val Pro Glu Ala 610 615 620 Arg Val Phe Lys Ala Ser Arg Ser Asn Asn Phe Tyr Leu Gly Met Leu 625 630 635 640 Leu Leu Ile Leu Phe Leu Ser Thr Met Pro Val Leu Tyr Met Ile Val 645 650 655 Ser Leu Pro Pro Ser Phe Asp Cys Gly Pro Phe Ser Gly Lys Asn Arg 660 665 670 Met Phe Glu Val Ile Gly Glu Thr Leu Glu His Asp Phe Pro Ser Trp 675 680 685 Met Ala Lys Ile Leu Arg Gln Leu Ser Asn Pro Gly Leu Val Ile Ala 690 695 700 Val Ile Leu Val Met Val Leu Ala Ile Tyr Tyr Leu Asn Ala Thr Ala 705 710 715 720 Lys Gly Gln Lys Ala Ala Asn Leu Asp Leu Lys Lys Lys Met Lys Met 725 730 735 Gln Ala Leu Glu Asn Lys Met Arg Asn Lys Lys Met Ala Ala Ala Arg 740 745 750 Ala Ala Ala Ala Ala Gly Arg Gln 755 760 <210> 43 <211> 1445 <212> PRT <213> Homo sapiens <400> 43 Met Glu Glu Gly His Gly Leu Asp Leu Thr Tyr Ile Thr Glu Arg Ile 1 5 10 15 Ile Ala Val Ser Phe Pro Ala Gly Cys Ser Glu Glu Ser Tyr Leu His 20 25 30 Asn Leu Gln Glu Val Thr Arg Met Leu Lys Ser Lys His Gly Asp Asn 35 40 45 Tyr Leu Val Leu Asn Leu Ser Glu Lys Arg Tyr Asp Leu Thr Lys Leu 50 55 60 Asn Pro Lys Ile Met Asp Val Gly Trp Pro Glu Leu His Ala Pro Pro 65 70 75 80 Leu Asp Lys Met Cys Thr Ile Cys Lys Ala Gln Glu Ser Trp Leu Asn 85 90 95 Ser Asn Leu Gln His Val Val Val Ile His Cys Arg Gly Gly Lys Gly 100 105 110 Arg Ile Gly Val Val Ile Ser Ser Tyr Met His Phe Thr Asn Val Ser 115 120 125 Ala Ser Ala Asp Gln Ala Leu Asp Arg Phe Ala Met Lys Lys Phe Tyr 130 135 140 Asp Asp Lys Val Ser Ala Leu Met Gln Pro Ser Gln Lys Arg Tyr Val 145 150 155 160 Gln Phe Leu Ser Gly Leu Leu Ser Gly Ser Val Lys Met Asn Ala Ser 165 170 175 Pro Leu Phe Leu His Phe Val Ile Leu His Gly Thr Pro Asn Phe Asp 180 185 190 Thr Gly Gly Val Cys Arg Pro Phe Leu Lys Leu Tyr Gln Ala Met Gln 195 200 205 Pro Val Tyr Thr Ser Gly Ile Tyr Asn Val Gly Pro Glu Asn Pro Ser 210 215 220 Arg Ile Cys Ile Val Ile Glu Pro Ala Gln Leu Leu Lys Gly Asp Val 225 230 235 240 Met Val Lys Cys Tyr His Lys Lys Tyr Arg Ser Ala Thr Arg Asp Val 245 250 255 Ile Phe Arg Leu Gln Phe His Thr Gly Ala Val Gln Gly Tyr Gly Leu 260 265 270 Val Phe Gly Lys Glu Asp Leu Asp Asn Ala Ser Lys Asp Asp Arg Phe 275 280 285 Pro Asp Tyr Gly Lys Val Glu Leu Val Phe Ser Ala Thr Pro Glu Lys 290 295 300 Ile Gln Gly Ser Glu His Leu Tyr Asn Asp His Gly Val Ile Val Asp 305 310 315 320 Tyr Asn Thr Thr Asp Pro Leu Ile Arg Trp Asp Ser Tyr Glu Asn Leu 325 330 335 Ser Ala Asp Gly Glu Val Leu His Thr Gln Gly Pro Val Asp Gly Ser 340 345 350 Leu Tyr Ala Lys Val Arg Lys Lys Ser Ser Ser Asp Pro Gly Ile Pro 355 360 365 Gly Gly Pro Gln Ala Ile Pro Ala Thr Asn Ser Pro Asp His Ser Asp 370 375 380 His Thr Leu Ser Val Ser Ser Asp Ser Gly His Ser Thr Ala Ser Ala 385 390 395 400 Arg Thr Asp Lys Thr Glu Glu Arg Leu Ala Pro Gly Thr Arg Arg Gly 405 410 415 Leu Ser Ala Gln Glu Lys Ala Glu Leu Asp Gln Leu Leu Ser Gly Phe 420 425 430 Gly Leu Glu Asp Pro Gly Ser Ser Leu Lys Glu Met Thr Asp Ala Arg 435 440 445 Ser Lys Tyr Ser Gly Thr Arg His Val Val Pro Ala Gln Val His Val 450 455 460 Asn Gly Asp Ala Ala Leu Lys Asp Arg Glu Thr Asp Ile Leu Asp Asp 465 470 475 480 Glu Met Pro His His Asp Leu His Ser Val Asp Ser Leu Gly Thr Leu 485 490 495 Ser Ser Ser Glu Gly Pro Gln Ser Ala His Leu Gly Pro Phe Thr Cys 500 505 510 His Lys Ser Ser Gln Asn Ser Leu Leu Ser Asp Gly Phe Gly Ser Asn 515 520 525 Val Gly Glu Asp Pro Gln Gly Thr Leu Val Pro Asp Leu Gly Leu Gly 530 535 540 Met Asp Gly Pro Tyr Glu Arg Glu Arg Thr Phe Gly Ser Arg Glu Pro 545 550 555 560 Lys Gln Pro Gln Pro Leu Leu Arg Lys Pro Ser Val Ser Ala Gln Met 565 570 575 Gln Ala Tyr Gly Gln Ser Ser Tyr Ser Thr Gln Thr Trp Val Arg Gln 580 585 590 Gln Gln Met Val Val Ala His Gln Tyr Ser Phe Ala Pro Asp Gly Glu 595 600 605 Ala Arg Leu Val Ser Arg Cys Pro Ala Asp Asn Pro Gly Leu Val Gln 610 615 620 Ala Gln Pro Arg Val Pro Leu Thr Pro Thr Arg Gly Thr Ser Ser Arg 625 630 635 640 Val Ala Val Gln Arg Gly Val Gly Ser Gly Pro His Pro Pro Asp Thr 645 650 655 Gln Gln Pro Ser Pro Ser Lys Ala Phe Lys Pro Arg Phe Pro Gly Asp 660 665 670 Gln Val Val Asn Gly Ala Gly Pro Glu Leu Ser Thr Gly Pro Ser Pro 675 680 685 Gly Ser Pro Thr Leu Asp Ile Asp Gln Ser Ile Glu Gln Leu Asn Arg 690 695 700 Leu Ile Leu Glu Leu Asp Pro Thr Phe Glu Pro Ile Pro Thr His Met 705 710 715 720 Asn Ala Leu Gly Ser Gln Ala Asn Gly Ser Val Ser Pro Asp Ser Val 725 730 735 Gly Gly Gly Leu Arg Ala Ser Ser Arg Leu Pro Asp Thr Gly Glu Gly 740 745 750 Pro Ser Arg Ala Thr Gly Arg Gln Gly Ser Ser Ala Glu Gln Pro Leu 755 760 765 Gly Gly Arg Leu Arg Lys Leu Ser Leu Gly Gln Tyr Asp Asn Asp Ala 770 775 780 Gly Gly Gln Leu Pro Phe Ser Lys Cys Ala Trp Gly Lys Ala Gly Val 785 790 795 800 Asp Tyr Ala Pro Asn Leu Pro Pro Phe Pro Ser Pro Ala Asp Val Lys 805 810 815 Glu Thr Met Thr Pro Gly Tyr Pro Gln Asp Leu Asp Ile Ile Asp Gly 820 825 830 Arg Ile Leu Ser Ser Lys Glu Ser Met Cys Ser Thr Pro Ala Phe Pro 835 840 845 Val Ser Pro Glu Thr Pro Tyr Val Lys Thr Ala Leu Arg His Pro Pro 850 855 860 Phe Ser Pro Pro Glu Pro Pro Leu Ser Ser Pro Ala Ser Gln His Lys 865 870 875 880 Gly Gly Arg Glu Pro Arg Ser Cys Pro Glu Thr Leu Thr His Ala Val 885 890 895 Gly Met Ser Glu Ser Pro Ile Gly Pro Lys Ser Thr Met Leu Arg Ala 900 905 910 Asp Ala Ser Ser Thr Pro Ser Phe Gln Gln Ala Phe Ala Ser Ser Cys 915 920 925 Thr Ile Ser Ser Asn Gly Pro Gly Gln Arg Arg Glu Ser Ser Ser Ser Ser 930 935 940 Ala Glu Arg Gln Trp Val Glu Ser Ser Pro Lys Pro Met Val Ser Leu 945 950 955 960 Leu Gly Ser Gly Arg Pro Thr Gly Ser Pro Leu Ser Ala Glu Phe Ser 965 970 975 Gly Thr Arg Lys Asp Ser Pro Val Leu Ser Cys Phe Pro Ser Glu 980 985 990 Leu Gln Ala Pro Phe His Ser His Glu Leu Ser Leu Ala Glu Pro Pro 995 1000 1005 Asp Ser Leu Ala Pro Ser Ser Gln Ala Phe Leu Gly Phe Gly Thr 1010 1015 1020 Ala Pro Val Gly Ser Gly Leu Pro Pro Glu Glu Asp Leu Gly Ala Leu 1025 1030 1035 1040 Leu Ala Asn Ser His Gly Ala Ser Pro Thr Pro Ser Ile Pro Leu Thr 1045 1050 1055 Ala Thr Gly Ala Ala Asp Asn Gly Phe Leu Ser His Asn Phe Leu Thr 1060 1065 1070 Val Ala Pro Gly His Ser Ser His His Ser Pro Gly Leu Gln Gly Gln 1075 1080 1085 Gly Val Thr Leu Pro Gly Gln Pro Pro Leu Pro Glu Lys Lys Arg Ala 1090 1095 1100 Ser Glu Gly Asp Arg Ser Leu Gly Ser Val Ser Pro Ser Ser Ser Gly 1105 1110 1115 1120 Phe Ser Ser Pro His Ser Gly Ser Thr Ile Ser Ile Pro Phe Pro Asn 1125 1130 1135 Val Leu Pro Asp Phe Ser Lys Ala Ser Glu Ala Ala Ser Pro Leu Pro 1140 1145 1150 Asp Ser Pro Gly Asp Lys Leu Val Ile Val Lys Phe Val Gln Asp Thr 1155 1160 1165 Ser Lys Phe Trp Tyr Lys Ala Asp Ile Ser Arg Glu Gln Ala Ile Ala 1170 1175 1180 Met Leu Lys Asp Lys Glu Pro Gly Ser Phe Ile Val Arg Asp Ser His 1185 1190 1195 1200 Ser Phe Arg Gly Ala Tyr Gly Leu Ala Met Lys Val Ala Thr Pro Pro 1205 1210 1215 Pro Ser Val Leu Gln Leu Asn Lys Lys Ala Gly Asp Leu Ala Asn Glu 1220 1225 1230 Leu Val Arg His Phe Leu Ile Glu Cys Thr Pro Lys Gly Val Arg Leu 1235 1240 1245 Lys Gly Cys Ser Asn Glu Pro Tyr Phe Gly Ser Leu Thr Ala Leu Val 1250 1255 1260 Cys Gln His Ser Ile Thr Pro Leu Ala Leu Pro Cys Lys Leu Leu Ile 1265 1270 1275 1280 Pro Glu Arg Asp Pro Leu Glu Glu Ile Ala Glu Ser Ser Pro Gln Thr 1285 1290 1295 Ala Ala Asn Ser Ala Ala Glu Leu Leu Lys Gln Gly Ala Ala Cys Asn 1300 1305 1310 Val Trp Tyr Leu Asn Ser Val Glu Met Glu Ser Leu Thr Gly His Gln 1315 1320 1325 Ala Ile Gln Lys Ala Leu Ser Ile Thr Leu Val Gln Glu Pro Pro Pro 1330 1335 1340 Val Ser Thr Val Val His Phe Lys Val Ser Ala Gln Gly Ile Thr Leu 1345 1350 1355 1360 Thr Asp Asn Gln Arg Lys Leu Phe Phe Arg Arg His Tyr Pro Val Asn 1365 1370 1375 Ser Val Ile Phe Cys Ala Leu Asp Pro Gln Asp Arg Lys Trp Ile Lys 1380 1385 1390 Asp Gly Pro Ser Ser Lys Val Phe Gly Phe Val Ala Arg Lys Gln Gly 1395 1400 1405 Ser Ala Thr Asp Asn Val Cys His Leu Phe Ala Glu His Asp Pro Glu 1410 1415 1420 Gln Pro Ala Ser Ala Ile Val Asn Phe Val Ser Lys Val Met Ile Gly 1425 1430 1435 1440 Ser Pro Lys Lys Val 1445 <210> 44 <211> 1556 <212> PRT <213> Homo sapiens <400> 44 Met Tyr Val Arg Val Ser Phe Asp Thr Lys Pro Asp Leu Leu Leu His 1 5 10 15 Leu Met Thr Lys Glu Trp Gln Leu Glu Leu Pro Lys Leu Leu Ile Ser 20 25 30 Val His Gly Gly Leu Gln Asn Phe Glu Leu Gln Pro Lys Leu Lys Gln 35 40 45 Val Phe Gly Lys Gly Leu Ile Lys Ala Ala Met Thr Thr Gly Ala Trp 50 55 60 Ile Phe Thr Gly Gly Val Asn Thr Gly Val Ile Arg His Val Gly Asp 65 70 75 80 Ala Leu Lys Asp His Ala Ser Lys Ser Arg Gly Lys Ile Cys Thr Ile 85 90 95 Gly Ile Ala Pro Trp Gly Ile Val Glu Asn Gln Glu Asp Leu Ile Gly 100 105 110 Arg Asp Val Val Arg Pro Tyr Gln Thr Met Ser Asn Pro Met Ser Lys 115 120 125 Leu Thr Val Leu Asn Ser Met His Ser His Phe Ile Leu Ala Asp Asn 130 135 140 Gly Thr Thr Gly Lys Tyr Gly Ala Glu Val Lys Leu Arg Arg Gln Leu 145 150 155 160 Glu Lys His Ile Ser Leu Gln Lys Ile Asn Thr Arg Ile Gly Gln Gly 165 170 175 Val Pro Val Val Ala Leu Ile Val Glu Gly Gly Pro Asn Val Ile Ser 180 185 190 Ile Val Leu Glu Tyr Leu Arg Asp Thr Pro Val Pro Val Val Val 195 200 205 Cys Asp Gly Ser Gly Arg Ala Ser Asp Ile Leu Ala Phe Gly His Lys 210 215 220 Tyr Ser Glu Glu Gly Gly Leu Ile Asn Glu Ser Leu Arg Asp Gln Leu 225 230 235 240 Leu Val Thr Ile Gln Lys Thr Phe Thr Tyr Thr Arg Thr Gln Ala Gln 245 250 255 His Leu Phe Ile Ile Leu Met Glu Cys Met Lys Lys Lys Lys Glu Leu Ile 260 265 270 Thr Val Phe Arg Met Gly Ser Glu Gly His Gln Asp Ile Asp Leu Ala 275 280 285 Ile Leu Thr Ala Leu Leu Lys Gly Ala Asn Ala Ser Ala Pro Asp Gln 290 295 300 Leu Ser Leu Ala Leu Ala Trp Asn Arg Val Asp Ile Ala Arg Ser Gln 305 310 315 320 Ile Phe Ile Tyr Gly Gln Gln Trp Pro Val Gly Ser Leu Glu Gln Ala 325 330 335 Met Leu Asp Ala Leu Val Leu Asp Arg Val Asp Phe Val Lys Leu Leu 340 345 350 Ile Glu Asn Gly Val Ser Met His Arg Phe Leu Thr Ile Ser Arg Leu 355 360 365 Glu Glu Leu Tyr Asn Thr Arg His Gly Pro Ser Asn Thr Leu Tyr His 370 375 380 Leu Val Arg Asp Val Lys Lys Arg Glu Tyr Pro Gly Phe Gly Trp Ile 385 390 395 400 Tyr Phe Lys Gly Asn Leu Pro Pro Asp Tyr Arg Ile Ser Leu Ile Asp 405 410 415 Ile Gly Leu Val Ile Glu Tyr Leu Met Gly Gly Ala Tyr Arg Cys Asn 420 425 430 Tyr Thr Arg Lys Arg Phe Arg Thr Leu Tyr His Asn Leu Phe Gly Pro 435 440 445 Lys Arg Asp Asp Ile Pro Leu Arg Arg Gly Arg Lys Thr Thr Lys Lys 450 455 460 Arg Glu Glu Glu Val Asp Ile Asp Leu Asp Asp Pro Glu Ile Asn His 465 470 475 480 Phe Pro Phe Pro Phe His Glu Leu Met Val Trp Ala Val Leu Met Lys 485 490 495 Arg Gln Lys Met Ala Leu Phe Phe Trp Gln His Gly Glu Glu Ala Met 500 505 510 Ala Lys Ala Leu Val Ala Cys Lys Leu Cys Lys Ala Met Ala His Glu 515 520 525 Ala Ser Glu Asn Asp Met Val Asp Asp Ile Ser Gln Glu Leu Asn His 530 535 540 Asn Ser Arg Asp Phe Gly Gln Leu Ala Val Glu Leu Leu Asp Gln Ser 545 550 555 560 Tyr Lys Gln Asp Glu Gln Leu Ala Met Lys Leu Leu Thr Tyr Glu Leu 565 570 575 Lys Asn Trp Ser Asn Ala Thr Cys Leu Gln Leu Ala Val Ala Ala Lys 580 585 590 His Arg Asp Phe Ile Ala His Thr Cys Ser Gln Met Leu Leu Thr Asp 595 600 605 Met Trp Met Gly Arg Leu Arg Met Arg Lys Asn Ser Gly Leu Lys Val 610 615 620 Ile Leu Gly Ile Leu Leu Pro Ser Ile Leu Ser Leu Glu Phe Lys 625 630 635 640 Asn Lys Asp Asp Met Pro Tyr Met Ser Gln Ala Gln Glu Ile His Leu 645 650 655 Gln Glu Lys Glu Ala Glu Glu Pro Glu Lys Pro Thr Lys Glu Lys Glu 660 665 670 Glu Glu Asp Met Glu Leu Thr Ala Met Leu Gly Arg Asn Asn Gly Glu 675 680 685 Ser Ser Arg Lys Lys Asp Glu Glu Glu Val Gln Ser Lys His Arg Leu 690 695 700 Ile Pro Leu Gly Arg Lys Ile Tyr Glu Phe Tyr Asn Ala Pro Ile Val 705 710 715 720 Lys Phe Trp Phe Tyr Thr Leu Ala Tyr Ile Gly Tyr Leu Met Leu Phe 725 730 735 Asn Tyr Ile Val Leu Val Lys Met Glu Arg Trp Pro Ser Thr Gln Glu 740 745 750 Trp Ile Val Ile Ser Tyr Ile Phe Thr Leu Gly Ile Glu Lys Met Arg 755 760 765 Glu Ile Leu Met Ser Glu Pro Gly Lys Leu Leu Gln Lys Val Lys Val 770 775 780 Trp Leu Gln Glu Tyr Trp Asn Val Thr Asp Leu Ile Ala Ile Leu Leu 785 790 795 800 Phe Ser Val Gly Met Ile Leu Arg Leu Gln Asp Gln Pro Phe Arg Ser 805 810 815 Asp Gly Arg Val Ile Tyr Cys Val Asn Ile Ile Tyr Trp Tyr Ile Arg 820 825 830 Leu Leu Asp Ile Phe Gly Val Asn Lys Tyr Leu Gly Pro Tyr Val Met 835 840 845 Met Ile Gly Lys Met Met Ile Asp Met Met Tyr Phe Val Ile Ile Met 850 855 860 Leu Val Val Leu Met Ser Phe Gly Val Ala Arg Gln Ala Ile Leu Phe 865 870 875 880 Pro Asn Glu Glu Pro Ser Trp Lys Leu Ala Lys Asn Ile Phe Tyr Met 885 890 895 Pro Tyr Trp Met Ile Tyr Gly Glu Val Phe Ala Asp Gln Ile Asp Pro 900 905 910 Pro Cys Gly Gln Asn Glu Thr Arg Glu Asp Gly Lys Ile Ile Gln Leu 915 920 925 Pro Pro Cys Lys Thr Gly Ala Trp Ile Val Pro Ala Ile Met Ala Cys 930 935 940 Tyr Leu Leu Val Ala Asn Ile Leu Leu Val Asn Leu Leu Ile Ala Val 945 950 955 960 Phe Asn Asn Thr Phe Phe Glu Val Lys Ser Ile Ser Asn Gln Val Trp 965 970 975 Lys Phe Gln Arg Tyr Gln Leu Ile Met Thr Phe His Glu Arg Pro Val 980 985 990 Leu Pro Pro Pro Leu Ile Ile Phe Ser His Met Thr Met Ile Phe Gln 995 1000 1005 His Leu Cys Cys Arg Trp Arg Lys His Glu Ser Asp Pro Asp Glu Arg 1010 1015 1020 Asp Tyr Gly Leu Lys Leu Phe Ile Thr Asp Asp Glu Leu Lys Lys Val 1025 1030 1035 1040 His Asp Phe Glu Glu Gln Cys Ile Glu Glu Tyr Phe Arg Glu Lys Asp 1045 1050 1055 Asp Arg Phe Asn Ser Ser Asn Asp Glu Arg Ile Arg Val Thr Ser Glu 1060 1065 1070 Arg Val Glu Asn Met Ser Met Arg Leu Glu Glu Val Asn Glu Arg Glu 1075 1080 1085 His Ser Met Lys Ala Ser Leu Gln Thr Val Asp Ile Arg Leu Ala Gln 1090 1095 1100 Leu Glu Asp Leu Ile Gly Arg Met Ala Thr Ala Leu Glu Arg Leu Thr 1105 1110 1115 1120 Gly Leu Glu Arg Ala Glu Ser Asn Lys Ile Arg Ser Arg Thr Ser Ser 1125 1130 1135 Asp Cys Thr Asp Ala Ala Tyr Ile Val Arg Gln Ser Ser Phe Asn Ser 1140 1145 1150 Gln Glu Gly Asn Thr Phe Lys Leu Gln Glu Ser Ile Asp Pro Ala Gly 1155 1160 1165 Glu Glu Thr Met Ser Pro Thr Ser Pro Thr Leu Met Pro Arg Met Arg 1170 1175 1180 Ser His Ser Phe Tyr Ser Val Asn Met Lys Asp Lys Gly Gly Ile Glu 1185 1190 1195 1200 Lys Leu Glu Ser Ile Phe Lys Glu Arg Ser Leu Ser Leu His Arg Ala 1205 1210 1215 Thr Ser Ser His Ser Val Ala Lys Glu Pro Lys Ala Pro Ala Ala Pro 1220 1225 1230 Ala Asn Thr Leu Ala Ile Val Pro Asp Ser Arg Arg Pro Ser Ser Cys 1235 1240 1245 Ile Asp Ile Tyr Val Ser Ala Met Asp Glu Leu His Cys Asp Ile Asp 1250 1255 1260 Pro Leu Asp Asn Ser Val Asn Ile Leu Gly Leu Gly Glu Pro Ser Phe 1265 1270 1275 1280 Ser Thr Pro Val Pro Ser Thr Ala Pro Ser Ser Ser Ala Tyr Ala Thr 1285 1290 1295 Leu Ala Pro Thr Asp Arg Pro Pro Ser Arg Ser Ile Asp Phe Glu Asp 1300 1305 1310 Ile Thr Ser Met Asp Thr Arg Ser Phe Ser Ser Asp Tyr Thr His Leu 1315 1320 1325 Pro Glu Cys Gln Asn Pro Trp Asp Ser Glu Pro Pro Met Tyr His Thr 1330 1335 1340 Ile Glu Arg Ser Lys Ser Ser Arg Tyr Leu Ala Thr Thr Pro Phe Leu 1345 1350 1355 1360 Leu Glu Glu Ala Pro Ile Val Lys Ser His Ser Phe Met Phe Ser Pro 1365 1370 1375 Ser Arg Ser Tyr Tyr Ala Asn Phe Gly Val Pro Val Lys Thr Ala Glu 1380 1385 1390 Tyr Thr Ser Ile Thr Asp Cys Ile Asp Thr Arg Cys Val Asn Ala Pro 1395 1400 1405 Gln Ala Ile Ala Asp Arg Ala Ala Phe Pro Gly Gly Leu Gly Asp Lys 1410 1415 1420 Val Glu Asp Leu Thr Cys Cys His Pro Glu Arg Glu Ala Glu Leu Ser 1425 1430 1435 1440 His Pro Ser Ser Asp Ser Glu Glu Asn Glu Ala Lys Gly Arg Arg Ala 1445 1450 1455 Thr Ile Ala Ile Ser Ser Gln Glu Gly Asp Asn Ser Glu Arg Thr Leu 1460 1465 1470 Ser Asn Asn Ile Thr Val Pro Lys Ile Glu Arg Ala Asn Ser Tyr Ser 1475 1480 1485 Ala Glu Glu Pro Ser Ala Pro Tyr Ala His Thr Arg Lys Ser Phe Ser 1490 1495 1500 Ile Ser Asp Lys Leu Asp Arg Gln Arg Asn Thr Ala Ser Leu Arg Asn 1505 1510 1515 1520 Pro Phe Gln Arg Ser Lys Ser Ser Lys Pro Glu Gly Arg Gly Asp Ser 1525 1530 1535 Leu Ser Met Arg Arg Leu Ser Arg Thr Ser Ala Phe Gln Ser Phe Glu 1540 1545 1550 Ser Lys His Asn 1555 <210> 45 <211> 527 <212> PRT <213> Homo sapiens <400> 45 Met Ile Leu Ser Ser Tyr Asn Thr Ile Gln Ser Val Phe Cys Cys Cys 1 5 10 15 Cys Cys Cys Ser Val Gln Lys Arg Gln Met Arg Thr Gln Ile Ser Leu 20 25 30 Ser Thr Asp Glu Glu Leu Pro Glu Lys Tyr Thr Gln Arg Arg Arg Pro 35 40 45 Trp Leu Ser Gln Leu Ser Asn Lys Lys Gln Ser Asn Thr Gly Arg Val 50 55 60 Gln Pro Ser Lys Arg Lys Pro Leu Pro Pro Leu Pro Pro Ser Glu Val 65 70 75 80 Ala Glu Glu Lys Ile Gln Val Lys Ala Leu Tyr Asp Phe Leu Pro Arg 85 90 95 Glu Pro Cys Asn Leu Ala Leu Arg Arg Ala Glu Glu Tyr Leu Ile Leu 100 105 110 Glu Lys Tyr Asn Pro His Trp Trp Lys Ala Arg Asp Arg Leu Gly Asn 115 120 125 Glu Gly Leu Ile Pro Ser Asn Tyr Val Thr Glu Asn Lys Ile Thr Asn 130 135 140 Leu Glu Ile Tyr Glu Trp Tyr His Arg Asn Ile Thr Arg Asn Gln Ala 145 150 155 160 Glu His Leu Leu Arg Gln Glu Ser Lys Glu Gly Ala Phe Ile Val Arg 165 170 175 Asp Ser Arg His Leu Gly Ser Tyr Thr Ile Ser Val Phe Met Gly Ala 180 185 190 Arg Arg Ser Thr Glu Ala Ala Ile Lys His Tyr Gln Ile Lys Lys Asn 195 200 205 Asp Ser Gly Gln Trp Tyr Val Ala Glu Arg His Ala Phe Gln Ser Ile 210 215 220 Pro Glu Leu Ile Trp Tyr His Gln His Asn Ala Ala Gly Leu Met Thr 225 230 235 240 Arg Leu Arg Tyr Pro Val Gly Leu Met Gly Ser Cys Leu Pro Ala Thr 245 250 255 Ala Gly Phe Ser Tyr Glu Lys Trp Glu Ile Asp Pro Ser Glu Leu Ala 260 265 270 Phe Ile Lys Glu Ile Gly Ser Gly Gln Phe Gly Val Val His Leu Gly 275 280 285 Glu Trp Arg Ser His Ile Gln Val Ala Ile Lys Ala Ile Asn Glu Gly 290 295 300 Ser Met Ser Glu Glu Asp Phe Ile Glu Glu Ala Lys Val Met Met Lys 305 310 315 320 Leu Ser His Ser Lys Leu Val Gln Leu Tyr Gly Val Cys Ile Gln Arg 325 330 335 Lys Pro Leu Tyr Ile Val Thr Glu Phe Met Glu Asn Gly Cys Leu Leu 340 345 350 Asn Tyr Leu Arg Glu Asn Lys Gly Lys Leu Arg Lys Glu Met Leu Leu 355 360 365 Ser Val Cys Gln Asp Ile Cys Glu Gly Met Glu Tyr Leu Glu Arg Asn 370 375 380 Gly Tyr Ile His Arg Asp Leu Ala Ala Arg Asn Cys Leu Val Ser Ser 385 390 395 400 Thr Cys Ile Val Lys Ile Ser Asp Phe Gly Met Thr Arg Tyr Val Leu 405 410 415 Asp Asp Glu Tyr Val Ser Ser Phe Gly Ala Lys Phe Pro Ile Lys Trp 420 425 430 Ser Pro Pro Glu Val Phe Leu Phe Asn Lys Tyr Ser Ser Lys Ser Asp 435 440 445 Val Trp Ser Phe Gly Val Leu Met Trp Glu Val Phe Thr Glu Gly Lys 450 455 460 Met Pro Phe Glu Asn Lys Ser Asn Leu Gln Val Val Glu Ala Ile Ser 465 470 475 480 Glu Gly Phe Arg Leu Tyr Arg Pro His Leu Ala Pro Met Ser Ile Tyr 485 490 495 Glu Val Met Tyr Ser Cys Trp His Glu Lys Pro Glu Gly Arg Pro Thr 500 505 510 Phe Ala Glu Leu Leu Arg Ala Val Thr Glu Ile Ala Glu Thr Trp 515 520 525 <210> 46 <211> 1090 <212> PRT <213> Homo sapiens <400> 46 Met Ala Thr Leu Leu Ser His Pro Gln Gln Arg Pro Pro Phe Leu Arg 1 5 10 15 Gln Ala Ile Lys Ile Arg Arg Arg Arg Val Arg Asp Leu Gln Asp Pro 20 25 30 Pro Pro Gln Met Ala Pro Glu Ile Gln Pro Ser His His Phe Ser 35 40 45 Pro Glu Gln Arg Ala Leu Leu Tyr Glu Asp Ala Leu Tyr Thr Val Leu 50 55 60 His Arg Leu Gly His Pro Glu Pro Asn His Val Thr Glu Ala Ser Glu 65 70 75 80 Leu Leu Arg Tyr Leu Gln Glu Ala Phe His Val Glu Pro Glu Glu His 85 90 95 Gln Gln Thr Leu Gln Arg Val Arg Glu Leu Glu Lys Pro Ile Phe Cys 100 105 110 Leu Lys Ala Thr Val Lys Gln Ala Lys Gly Ile Leu Gly Lys Asp Val 115 120 125 Ser Gly Phe Ser Asp Pro Tyr Cys Leu Leu Gly Ile Glu Gln Gly Val 130 135 140 Gly Val Pro Gly Gly Ser Pro Gly Ser Arg His Arg Gln Lys Ala Val 145 150 155 160 Val Arg His Thr Ile Pro Glu Glu Glu Thr His Arg Thr Gln Val Ile 165 170 175 Thr Gln Thr Leu Asn Pro Val Trp Asp Glu Thr Phe Ile Leu Glu Phe 180 185 190 Glu Asp Ile Thr Asn Ala Ser Phe His Leu Asp Met Trp Asp Leu Asp 195 200 205 Thr Val Glu Ser Val Arg Gln Lys Leu Gly Glu Leu Thr Asp Leu His 210 215 220 Gly Leu Arg Arg Ile Phe Lys Glu Ala Arg Lys Asp Lys Gly Gln Asp 225 230 235 240 Asp Phe Leu Gly Asn Val Val Leu Arg Leu Gln Asp Leu Arg Cys Arg 245 250 255 Glu Asp Gln Trp Tyr Pro Leu Glu Pro Arg Thr Glu Thr Tyr Pro Asp 260 265 270 Arg Gly Gln Cys His Leu Gln Phe Gln Leu Ile His Lys Arg Arg Ala 275 280 285 Thr Ser Ala Ser Arg Ser Gln Pro Ser Tyr Thr Val His Leu His Leu 290 295 300 Leu Gln Gln Leu Val Ser His Glu Val Thr Gln His Glu Ala Gly Ser 305 310 315 320 Thr Ser Trp Asp Gly Ser Leu Ser Pro Gln Ala Ala Thr Val Leu Phe 325 330 335 Leu His Ala Thr Gln Lys Asp Leu Ser Asp Phe His Gln Ser Met Ala 340 345 350 Gln Trp Leu Ala Tyr Ser Arg Leu Tyr Gln Ser Leu Glu Phe Pro Ser 355 360 365 Ser Cys Leu Leu His Pro Ile Thr Ser Ile Glu Tyr Gln Trp Ile Gln 370 375 380 Gly Arg Leu Lys Ala Glu Gln Gln Glu Glu Leu Ala Ala Ser Phe Ser 385 390 395 400 Ser Leu Leu Thr Tyr Gly Leu Ser Leu Ile Arg Arg Phe Arg Ser Val 405 410 415 Phe Pro Leu Ser Val Ser Asp Ser Pro Ala Arg Leu Gln Ser Leu Leu 420 425 430 Arg Val Leu Val Gln Met Cys Lys Met Lys Ala Phe Gly Glu Leu Cys 435 440 445 Pro Asn Thr Ala Pro Leu Pro Gln Leu Val Thr Glu Ala Leu Gln Thr 450 455 460 Gly Thr Thr Glu Trp Phe His Leu Lys Gln Gln His His Gln Pro Met 465 470 475 480 Val Gln Gly Ile Pro Glu Ala Gly Lys Ala Leu Leu Gly Leu Val Gln 485 490 495 Asp Val Ile Gly Asp Leu His Gln Cys Gln Arg Thr Trp Asp Lys Ile 500 505 510 Phe His Asn Thr Leu Lys Ile His Leu Phe Ser Met Ala Phe Arg Glu 515 520 525 Leu Gln Trp Leu Val Ala Lys Arg Val Gln Asp His Thr Thr Val Val 530 535 540 Gly Asp Val Val Ser Pro Glu Met Gly Glu Ser Leu Phe Gln Leu Tyr 545 550 555 560 Ile Ser Leu Lys Glu Leu Cys Gln Leu Arg Met Ser Ser Ser Glu Arg 565 570 575 Asp Gly Val Leu Ala Leu Asp Asn Phe His Arg Trp Phe Gln Pro Ala 580 585 590 Ile Pro Ser Trp Leu Gln Lys Thr Tyr Asn Glu Ala Leu Ala Arg Val 595 600 605 Gln Arg Ala Val Gln Met Asp Glu Leu Val Pro Leu Gly Glu Leu Thr 610 615 620 Lys His Ser Thr Ser Ala Val Asp Leu Ser Thr Cys Phe Ala Gln Ile 625 630 635 640 Ser His Thr Ala Arg Gln Leu Asp Trp Pro Asp Pro Glu Glu Ala Phe 645 650 655 Met Ile Thr Val Lys Phe Val Glu Asp Thr Cys Arg Leu Ala Leu Val 660 665 670 Tyr Cys Ser Leu Ile Lys Ala Arg Ala Arg Glu Leu Ser Ser Gly Gln 675 680 685 Lys Asp Gln Gly Gln Ala Ala Asn Met Leu Cys Val Val Val Val Asn Asp 690 695 700 Met Glu Gln Leu Arg Leu Val Ile Gly Lys Leu Pro Ala Gln Leu Ala 705 710 715 720 Trp Glu Ala Leu Glu Gln Arg Val Gly Ala Val Leu Glu Gln Gly Gln 725 730 735 Leu Gln Asn Thr Leu His Ala Gln Leu Gln Ser Ala Leu Ala Gly Leu 740 745 750 Gly His Glu Ile Arg Thr Gly Val Arg Thr Leu Ala Glu Gln Leu Glu 755 760 765 Val Gly Ile Ala Lys His Ile Gln Lys Leu Val Gly Val Arg Glu Ser 770 775 780 Val Leu Pro Glu Asp Ala Ile Leu Pro Leu Met Lys Phe Leu Glu Val 785 790 795 800 Glu Leu Cys Tyr Met Asn Thr Asn Leu Val Gln Glu Asn Phe Ser Ser 805 810 815 Leu Leu Thr Leu Leu Trp Thr His Thr Leu Thr Val Leu Val Glu Ala 820 825 830 Ala Ala Ser Gln Arg Ser Ser Ser Leu Ala Ser Asn Arg Leu Lys Ile 835 840 845 Ala Leu Gln Asn Leu Glu Ile Cys Phe His Ala Glu Gly Cys Gly Leu 850 855 860 Pro Pro Lys Ala Leu His Thr Ala Thr Phe Gln Ala Leu Gln Arg Asp 865 870 875 880 Leu Glu Leu Gln Ala Ala Ser Ser Arg Glu Leu Ile Arg Lys Tyr Phe 885 890 895 Cys Ser Arg Ile Gln Gln Gln Ala Glu Thr Thr Ser Glu Glu Leu Gly 900 905 910 Ala Val Thr Val Lys Ala Ser Tyr Arg Ala Ser Glu Gln Lys Leu Arg 915 920 925 Val Glu Leu Leu Ser Ala Ser Ser Leu Leu Pro Leu Asp Ser Asn Gly 930 935 940 Ser Ser Asp Pro Phe Val Gln Leu Thr Leu Glu Pro Arg His Glu Phe 945 950 955 960 Pro Glu Leu Ala Ala Arg Glu Thr Gln Lys His Lys Lys Asp Leu His 965 970 975 Pro Leu Phe Asp Glu Thr Phe Glu Phe Leu Val Pro Ala Glu Pro Cys 980 985 990 Arg Lys Ala Gly Ala Cys Leu Leu Leu Thr Val Leu Asp Tyr Asp Thr 995 1000 1005 Leu Gly Ala Asp Asp Leu Glu Gly Glu Ala Phe Leu Pro Leu Arg Glu 1010 1015 1020 Val Pro Gly Leu Ser Gly Ser Glu Glu Pro Gly Glu Val Pro Gln Thr 1025 1030 1035 1040 Arg Leu Pro Leu Thr Tyr Pro Ala Pro Asn Gly Asp Pro Ile Leu Gln 1045 1050 1055 Leu Leu Glu Gly Arg Lys Gly Asp Arg Glu Ala Gln Val Phe Val Arg 1060 1065 1070 Leu Arg Arg His Arg Ala Lys Gln Ala Ser Gln His Ala Leu Arg Pro 1075 1080 1085 Ala Pro 1090 <210> 47 <211> 478 <212> PRT <213> Homo sapiens <400> 47 Met Gly Arg Lys Lys Lys Lys Gln Leu Lys Pro Trp Cys Trp Tyr Cys 1 5 10 15 Asn Arg Asp Phe Asp Asp Glu Lys Ile Leu Ile Gln His Gln Lys Ala 20 25 30 Lys His Phe Lys Cys His Ile Cys His Lys Lys Leu Tyr Thr Gly Pro 35 40 45 Gly Leu Ala Ile His Cys Met Gln Val His Lys Glu Thr Ile Asp Ala 50 55 60 Val Pro Asn Ala Ile Pro Gly Arg Thr Asp Ile Glu Leu Glu Ile Tyr 65 70 75 80 Gly Met Glu Gly Ile Pro Glu Lys Asp Met Asp Glu Arg Arg Arg Leu 85 90 95 Leu Glu Gln Lys Thr Gln Glu Ser Gln Lys Lys Lys Gln Gln Asp Asp 100 105 110 Ser Asp Glu Tyr Asp Asp Asp Asp Ser Ala Ala Ser Thr Ser Phe Gln 115 120 125 Pro Gln Pro Val Gln Pro Gln Gln Gly Tyr Ile Pro Pro Met Ala Gln 130 135 140 Pro Gly Leu Pro Pro Val Pro Gly Ala Pro Gly Met Pro Pro Gly Ile 145 150 155 160 Pro Pro Leu Met Pro Gly Val Pro Pro Leu Met Pro Gly Met Pro Pro 165 170 175 Val Met Pro Gly Met Pro Pro Gly Met Met Pro Met Gly Gly Met Met 180 185 190 Pro Pro Gly Pro Gly Ile Pro Pro Leu Met Pro Gly Met Pro Pro Gly 195 200 205 Met Pro Pro Pro Val Pro Arg Pro Gly Ile Pro Pro Met Thr Gln Ala 210 215 220 Gln Ala Val Ser Ala Pro Gly Ile Leu Asn Arg Pro Pro Ala Pro Thr 225 230 235 240 Ala Thr Val Pro Ala Pro Gln Pro Pro Val Thr Lys Pro Leu Phe Pro 245 250 255 Ser Ala Gly Gln Met Gly Thr Pro Val Thr Ser Ser Ser Ser Thr Ala Ser 260 265 270 Ser Asn Ser Glu Ser Leu Ser Ala Ser Ser Lys Ala Leu Phe Pro Ser 275 280 285 Thr Ala Gln Ala Gln Ala Ala Val Gln Gly Pro Val Gly Thr Asp Phe 290 295 300 Lys Pro Leu Asn Ser Thr Pro Ala Thr Thr Thr Glu Pro Pro Lys Pro 305 310 315 320 Thr Phe Pro Ala Tyr Thr Gln Ser Thr Ala Ser Thr Thr Ser Thr Thr 325 330 335 Asn Ser Thr Ala Ala Lys Pro Ala Ala Ser Ile Thr Ser Lys Pro Ala 340 345 350 Thr Leu Thr Thr Thr Ser Ala Thr Ser Lys Leu Ile His Pro Asp Glu 355 360 365 Asp Ile Ser Leu Glu Glu Arg Arg Ala Gln Leu Pro Lys Tyr Gln Arg 370 375 380 Asn Leu Pro Arg Pro Gly Gln Ala Pro Ile Gly Asn Pro Pro Val Gly 385 390 395 400 Pro Ile Gly Gly Met Met Pro Pro Gln Pro Gly Ile Pro Gln Gln Gln 405 410 415 Gly Met Arg Pro Pro Met Pro Pro His Gly Gln Tyr Gly Gly His His 420 425 430 Gln Gly Met Pro Gly Tyr Leu Pro Gly Ala Met Pro Pro Tyr Gly Gln 435 440 445 Gly Pro Pro Met Val Pro Pro Tyr Gln Gly Gly Pro Pro Arg Pro Pro 450 455 460 Met Gly Met Arg Pro Val Met Ser Gln Gly Gly Arg Tyr 465 470 475 <210> 48 <211> 671 <212> PRT <213> Homo sapiens <400> 48 Met Gln Phe Val Ser Thr Arg Pro Gln Pro Gln Gln Leu Gly Ile Gln 1 5 10 15 Gly Leu Gly Leu Asp Ser Gly Ser Trp Ser Trp Ala Gln Ala Leu Pro 20 25 30 Pro Glu Glu Val Cys His Gln Glu Pro Ala Leu Arg Gly Glu Met Ala 35 40 45 Glu Gly Met Pro Pro Met Gln Ala Gln Glu Trp Asp Met Asp Ala Arg 50 55 60 Arg Pro Met Pro Phe Gln Phe Pro Pro Phe Pro Asp Arg Ala Pro Val 65 70 75 80 Phe Pro Asp Arg Met Met Arg Glu Pro Gln Leu Pro Thr Ala Glu Ile 85 90 95 Ser Leu Trp Thr Val Val Ala Ala Ile Gln Ala Val Glu Arg Lys Val 100 105 110 Asp Ala Gln Ala Ser Gln Leu Leu Asn Leu Glu Gly Arg Thr Gly Thr 115 120 125 Ala Glu Lys Lys Leu Ala Asp Cys Glu Lys Thr Ala Val Glu Phe Gly 130 135 140 Asn His Met Glu Ser Lys Trp Ala Val Leu Gly Thr Leu Leu Gln Glu 145 150 155 160 Tyr Gly Leu Leu Gln Arg Arg Leu Glu Asn Leu Glu Asn Leu Leu Arg 165 170 175 Asn Arg Asn Phe Trp Val Leu Arg Leu Pro Pro Gly Ser Lys Gly Glu 180 185 190 Ala Pro Lys Val Pro Val Thr Phe Val Asp Ile Ala Val Tyr Phe Ser 195 200 205 Glu Asp Glu Trp Lys Asn Leu Asp Glu Trp Gln Lys Glu Leu Tyr Asn 210 215 220 Asn Leu Val Lys Glu Asn Tyr Lys Thr Leu Met Ser Leu Asp Ala Glu 225 230 235 240 Gly Ser Val Pro Lys Pro Asp Ala Pro Val Gln Ala Glu Pro Arg Glu 245 250 255 Glu Pro Cys Val Trp Glu Gln Arg His Pro Glu Glu Arg Glu Ile Pro 260 265 270 Met Asp Pro Glu Ala Gly Ala Glu Pro Leu Val Pro Ala Gln Asp Ala 275 280 285 Ser Ser Gln Val Lys Arg Glu Asp Thr Leu Cys Val Arg Gly Gln Arg 290 295 300 Gly Leu Glu Glu Arg Ala Ile Pro Thr Glu Ser Ile Thr Asp Ser Pro 305 310 315 320 Ile Ser Ala Gln Asp Leu Leu Ser Arg Ile Lys Gln Glu Glu His Gln 325 330 335 Cys Val Trp Asp Gln Gln Asp Leu Ala Asp Arg Asp Ile Pro Thr Asp 340 345 350 Pro Asn Ser Glu Ser Leu Ile Ser Ala His Asp Ile Leu Ser Trp Ile 355 360 365 Lys Gln Glu Glu Gln Pro Tyr Pro Trp Gly Pro Arg Asp Ser Met Asp 370 375 380 Gly Glu Leu Gly Leu Asp Ser Gly Pro Ser Asp Ser Leu Leu Met Val 385 390 395 400 Lys Asn Pro Pro Pro Ala Pro Pro Gln Pro Gln Pro Gln Pro Gln Pro 405 410 415 Pro Gln Pro Gln Leu Gln Ser Gln Pro Gln Pro Gln Ser Leu Pro Pro 420 425 430 Ile Ala Val Ala Glu Asn Pro Gly Gly Pro Pro Ser Arg Gly Leu Leu 435 440 445 Asp Asp Gly Phe Gln Val Leu Pro Gly Glu Arg Gly Ser Gly Glu Ala 450 455 460 Pro Pro Gly Gly Asp Arg Ser Thr Gly Gly Gly Gly Gly Asp Gly Gly 465 470 475 480 Gly Gly Gly Gly Gly Ala Glu Ala Gly Thr Gly Ala Gly Gly Gly Cys 485 490 495 Gly Ser Cys Cys Pro Gly Gly Leu Arg Arg Ser Leu Leu Leu His Gly 500 505 510 Ala Arg Ser Lys Pro Tyr Ser Cys Pro Glu Cys Gly Lys Ser Phe Gly 515 520 525 Val Arg Lys Ser Leu Ile Ile His His Arg Ser His Thr Lys Glu Arg 530 535 540 Pro Tyr Glu Cys Ala Glu Cys Glu Lys Ser Phe Asn Cys His Ser Gly 545 550 555 560 Leu Ile Arg His Gln Met Thr His Arg Gly Glu Arg Pro Tyr Lys Cys 565 570 575 Ser Glu Cys Glu Lys Thr Tyr Ser Arg Lys Glu His Leu Gln Asn His 580 585 590 Gln Arg Leu His Thr Gly Glu Arg Pro Phe Gln Cys Ala Leu Cys Gly 595 600 605 Lys Ser Phe Ile Arg Lys Gln Asn Leu Leu Lys His Gln Arg Ile His 610 615 620 Thr Gly Glu Arg Pro Tyr Thr Cys Gly Glu Cys Gly Lys Ser Phe Arg 625 630 635 640 Tyr Lys Glu Ser Leu Lys Asp His Leu Arg Val His Ser Gly Gly Pro 645 650 655 Gly Pro Gly Ala Pro Arg Gln Leu Pro Pro Pro Glu Arg Asp 660 665 670

Claims (10)

A2ML1 gene mutation, ANAPC1 gene mutation, ARNT2 gene mutation, ASIC5 gene mutation, BIRC6 gene mutation, BTBD10 gene mutation, EDRF1 gene mutation, CFHR4 gene mutation, CLHC1 gene mutation, CTNND1 gene mutation, DCAF4 gene mutation, DHX37 gene mutation, EPAS1 gene mutation, FBN2 gene mutation, GLDC gene mutation, GRIA2 gene mutation, GUCY1A2 gene mutation, ITGA3 gene mutation, ITGA4 gene mutation, KIF19 gene mutation, KIF1B gene mutation, LPIN1 gene mutation, MAATS1 gene mutation, MCM8 gene mutation, MCTP1 gene mutation, MED1 gene mutation, MTUS2 gene mutation, NAV3 gene mutation, NME9 gene mutation, NOC3L gene mutation, NRXN3 gene mutation, PIK3C2A gene mutation, POLK gene mutation, PRKG2 gene mutation, RIN3 gene mutation, SCUBE2 gene mutation, SLC45A1 gene mutation, SORL1 gene mutation, SP4 gene mutation, TBC1D9 gene mutation, TEK gene mutation, TMC1 gene mutation, TNS3 gene mutation, TRPM3 gene mutation, TXK gene mutation, UNC13D gene mutation, ZNF207 gene mutation and ZNF282 gene mutation comprising at least one selected from the group consisting of A composition for prognostic diagnosis of bladder cancer, comprising a reagent capable of detecting a survival-specific marker of a bladder cancer patient. The method according to claim 1,
The reagent is a composition comprising one or more selected from the group consisting of primers, probes, aptamers and antibodies. The method according to claim 1,
The survival-specific marker is ANAPC1 gene mutation, BTBD10 gene mutation, DHX37 gene mutation, GRIA2 gene mutation, GUCY1A2 gene mutation, ITGA3 gene mutation, KIF19 gene mutation, KIF1B gene mutation, MAATS1 gene mutation , MED1 gene mutation, MTUS2 gene mutation, NAV3 gene mutation, NOC3L gene mutation, PIK3C2A gene mutation, SCUBE2 gene mutation, SLC45A1 gene mutation, TBC1D9 gene mutation and ZNF282 gene mutation at least one composition. A2ML1 gene mutation, ANAPC1 gene mutation, ARNT2 gene mutation, ASIC5 gene mutation, BIRC6 gene mutation, BTBD10 gene mutation, EDRF1 gene mutation, CFHR4 gene mutation, CLHC1 gene mutation, CTNND1 gene mutation, DCAF4 gene mutation, DHX37 gene mutation, EPAS1 gene mutation, FBN2 gene mutation, GLDC gene mutation, GRIA2 gene mutation, GUCY1A2 gene mutation, ITGA3 gene mutation, ITGA4 gene mutation, KIF19 gene mutation, KIF1B gene mutation, LPIN1 gene mutation, MAATS1 gene mutation, MCM8 gene mutation, MCTP1 gene mutation, MED1 gene mutation, MTUS2 gene mutation, NAV3 gene mutation, NME9 gene mutation, NOC3L gene mutation, NRXN3 gene mutation, PIK3C2A gene mutation, POLK gene mutation, PRKG2 gene mutation, RIN3 gene mutation, SCUBE2 gene mutation, SLC45A1 gene mutation, SORL1 gene mutation, SP4 gene mutation, TBC1D9 gene mutation, TEK gene mutation, TMC1 gene mutation, TNS3 gene mutation, TRPM3 gene mutation, TXK gene mutation, UNC13D gene mutation, ZNF207 gene mutation and ZNF282 gene mutation comprising at least one selected from the group consisting of A kit for prognostic diagnosis of bladder cancer comprising a reagent capable of detecting a survival-specific marker of a bladder cancer patient. 5. The method according to claim 4,
The reagent is a kit comprising at least one selected from the group consisting of primers, probes, aptamers and antibodies. 5. The method according to claim 4,
The survival-specific marker is ANAPC1 gene mutation, BTBD10 gene mutation, DHX37 gene mutation, GRIA2 gene mutation, GUCY1A2 gene mutation, ITGA3 gene mutation, KIF19 gene mutation, KIF1B gene mutation, MAATS1 gene mutation , MED1 gene mutation, MTUS2 gene mutation, NAV3 gene mutation, NOC3L gene mutation, PIK3C2A gene mutation, SCUBE2 gene mutation, SLC45A1 gene mutation, TBC1D9 gene mutation and ZNF282 gene mutation At least one kit. preparing sample DNA from a sample of a bladder cancer patient;
Using the composition for prognostic diagnosis of any one of claims 1 to 3 or the kit for prognostic diagnosis of bladder cancer of any one of claims 4 to 6 with respect to the sample DNA, confirming the presence or absence of a survival-specific marker; including; A method of providing information necessary for prognostic diagnosis of bladder cancer patients. 8. The method of claim 7,
The method further comprising the step of amplifying the sample DNA prepared from the bladder cancer patient sample. 8. The method of claim 7,
Among the survival-specific markers, at least one selected from the group consisting of a mutation in the ASIC5 gene, a mutation in the DCAF4 gene, a mutation in the EPAS1 gene, a mutation in the NME9 gene, a mutation in the NRXN3 gene, and a mutation in the ZNF282 gene is confirmed. A method further comprising; determining that the survival rate is lower or the recurrence rate is higher than that of a person whose specific marker is not identified. 8. The method of claim 7,
Among the survival-specific markers, CTNND1 gene mutation, EPS15L1 gene mutation, FBN2 gene mutation, GLDC gene mutation, GRIA2 gene mutation, GUCY1A2 gene mutation, ITGA3 gene mutation, ITGA4 gene mutation, KIF19 gene mutation , KIF1B gene mutation, MAATS1 gene mutation, MCM8 gene mutation, MCTP1 gene mutation, MED1 gene mutation, MTUS2 gene mutation, NAV3 gene mutation, NOC3L gene mutation, PIK3C2A gene mutation, POLK gene mutation , PRKG2 gene mutation, RIN3 gene mutation, SCUBE2 gene mutation, SLC45A1 gene mutation, SORL2 gene mutation, SP4 gene mutation, TBC1D9 gene mutation, TEK gene mutation, TMC1 gene mutation, TNS3 gene mutation When at least one selected from the group consisting of , TRPM3 gene mutation, TXK gene mutation, UNC13D gene mutation, and ZNF207 gene mutation is identified, the survival rate is higher or the recurrence rate is higher than that of those whose survival-specific marker is not identified. The method further comprising; determining that it is low.

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