GENDER-SPECIFIC MARKERS FOR DIAGNOSING PROGNOSIS AND DETERMINING TREATMENT STRATEGY FOR RENAL CANCER PATIENTS

Abstract

The present invention relates to markers for diagnosing the difference in effects of renal cancer treatment or the prognosis of renal cancer patients, according to the gender of renal cancer patients. The survival rate and recurrence rate of renal cancer of a particular gender respectively relate to the mutation of genes, of the present invention, in renal cancer patients, and thus the mutated genes of the present invention can be used as markers in predicting, on the basis of gender, the difference in effects of renal cancer treatment or the prognosis of renal cancer patients.

Description

TECHNICAL FIELD

[0001] The present invention relates to a marker for diagnosing prognosis of a patient with kidney cancer, a kit for diagnosing prognosis of a patient with kidney cancer including the same, and a method of providing information required to diagnose the prognosis of kidney cancer and determine a therapeutic strategy for kidney cancer using the kit for diagnosing prognosis of a patient with kidney cancer.

BACKGROUND ART

[0002] The kidney is an important urinary organ that serves to excrete waste materials from the body by filtering blood to generate urine. Also, the kidney is an important endocrine organ that produces hormones such as angiotensin that controls the blood pressure, erythropoietin as a haemopoietic factor, and the like.

[0003] Tumors occurring in the kidney include renal cell carcinoma arising from the adults, Wilms' tumor arising from the children, sarcoma as a rare tumor, and the like. Later on, the renal cell carcinoma as a malignant tumor having the highest incidence rate is referred to as kidney cancer. In Japan, the kidney cancer develops at an incidence frequency of approximately 2.5 per every 100,000 persons. In this case, the kidney cancer tends to occur at a higher frequency for men, that is, the proportion of men and women is 2 to 3:1. Among the urological malignant tumors, the kidney cancer is the most common tumor following prostate cancer and bladder cancer. The kidney cancer refers to renal cell carcinoma that develops mostly in the parenchyma (including medulla and cortex in which cells producing urine in the kidney are held together) of the kidney.

[0004] A genetic factor is known to be one of risk factors for kidney cancer, but such risk factors generally include smoking, excessive fat intake, and the like. Also, it has been know that the incidence rate of tumor is high in patients receiving dialysis for a long time.

[0005] In the case of kidney cancer, patients rarely have any observable symptoms when a tumor has the maximum diameter of 5 cm or less. Generally, the kidney cancer is often found when patients take a medical examination through a CT scan, and the like. Hematuria, celioncus, pain, and the like appear as the symptoms of large tumors. Also, pyrexy, weight loss, anaemia, and the like are often caused as the systemic symptoms, and erythrocytosis, hypertension, hypercalcemia, and the like are rarely caused by endocrine factors. Meanwhile, development of phlebismus or varicocele in the abdominal wall often occurs by tremors in the inferior vena cava of the kidney. Approximately 20% of the kidney cancers are found from the metastasis to the lungs or bone. Because tumor has a strong tendency to spread into the vein in the case of kidney cancer, the kidney cancer easily metastasizes into other organs.

[0006] Kidney cancer has few symptoms when it has a small tumor size, but has symptoms only when the tumor grows to push organs. Therefore, because the diagnosis of the kidney cancer is often delayed, the metastasis of kidney cancer into other organs is found in approximately 30% of patients, compared to when the kidney cancer is diagnosed at an early stage. The most common symptom is hematuria, but is found only in 60% of the patients. On the contrary, because patients have symptoms such as dyspnoea, cough, headaches, and the like depending on the metastasized sites, the patients who are diagnosed with kidney cancer due to such metastatic symptoms also account for 30% of the entire patients. Because hypertension, hypercalcemia, hepatic dysfunction, and the like may be caused by certain hormones especially produced by cancer cells, tumors may be often found while checking these other symptoms in kidney cancer. However, there are many current cases in which tumors are found by chance in imaging tests while patients receive medical checkups without any symptoms. In this case, because the tumors are generally found at early stages, the results of tumor treatment have been relatively successful. Therefore, it has been known that it is very important to diagnose such kidney cancer.

[0007] In U.S., patients with kidney cancer account for approximately 3% of adult cancer patients, and approximately 32,000 cancer patients are newly reported every year. Also, approximately 12,000 cases are assumed to die from kidney cancer, with an increasing incidence frequency worldwide every year. In Korea, the incidence frequency of kidney cancer is reported to be lower than that in U.S. Therefore, the National Cancer Registry data (2012) reported that 1,578 new cases of cancer patients are registered so that it accounts for 1.6% of the total number of cancer occurrences. Kidney cancer occurs commonly in people between 40 to 60 years old, and the current state of cancer incidence by gender (National Cancer Registry data on 2012) reports that kidney cancer occurs most commonly in people in their 60s (479 cases, 30.2%), followed by 50s (412 cases, 26.0%), and 40s (268 cases, 16.9%) in the corresponding order thereof When patients with kidney cancer undergo surgery to remove the tumor after the onset of kidney cancer, the patients have a high survival rate. However, because the patients have no clear symptoms at an early stage, it is difficult to diagnose kidney cancer at this stage. For these reasons, there is a need for development of a marker capable of diagnosing kidney cancer at an early stage and checking the patients' remaining lives after the onset of cancer.

[0008] Transglutaminase 2 (Registered Korean Patent No. 1267580) is disclosed as a marker used to detect or diagnose kidney cancer in humans. Although markers for diagnosing cancers including kidney cancer have been developed, there is no research on markers capable of determining the prognosis of patients with kidney cancer, particularly the relationship between the gender of patients with kidney cancer and the mutation of a certain gene.

[0009] To develop a therapeutic agent for diagnosing kidney cancer or healing patients with kidney cancer so as to determine a therapeutic strategy, the present inventors have conducted research on the relationship between the gene mutation and the gender of the patients found in the patients with kidney cancer on the basis of the need for development of the markers capable of diagnosing the prognosis of the patients with kidney cancer.

DISCLOSURE

Technical Problem

[0010] To apply a suitable therapeutic strategy to patients with kidney cancer, a development of markers which aid in predicting the prognosis of patients with kidney cancer and determining a therapeutic strategy thereof is needed. Therefore, it is an object of the present invention to provide a marker which aids in predicting the prognosis of patients with kidney cancer and determining a therapeutic strategy thereof based on the gender of the patients with kidney cancer.

Technical Solution

[0011] To solve the above problems, according to an aspect of the present invention, there is provided a kit for providing information required to predict a therapeutic effect against kidney cancer or diagnose prognosis of a patient with kidney cancer according to the gender of the patient with kidney cancer, wherein the kit is able to detect a gender-specific marker that is a mutation of a gene coding for at least one selected from the group consisting of ACSS3, ADAM21, AFF2, ALG13, BAP1, BRWD3, COL4A5, CPEB1, ERBB2, HSP90AA1, IRAK1, KDMSC, KDM6A, LRP12, NCOA6, NHS, RGAG1, SCAF1, SH3TC1, TBC1D8B, TET2, TEX13A, ULK3, WNK3, ARSF, CFP, FAM47A, PHF16, ZNF449, and SCRN1.

[0012] According to another aspect of the present invention, there is provided a method of providing information required to verify a difference in therapeutic effect against kidney cancer according to the gender of patients with kidney cancer. In this case, the method includes preparing a DNA test sample from a sample of a patient with kidney cancer whose gender is identified; amplifying the DNA test sample using the kit; determining whether or not there is a gender-specific marker specific to a gender group of target patients from the results of amplification; treating the patient with kidney cancer, in which the gender-specific marker is identified, with any candidate material for treating kidney cancer or healing the patient with kidney cancer using any method; and choosing any candidate material for treating kidney cancer or any method of treating kidney cancer as a therapeutic candidate material or a therapeutic method, which is suitable for the gender group of patients with kidney cancer in which the gender-specific marker is identified, when the any candidate material or the any method is used to treat kidney cancer.

[0013] According to still another aspect of the present invention, there is provided a method of providing information required to diagnose prognosis of kidney cancer according to the gender of a patient with kidney cancer. In this case, the method includes preparing a DNA test sample from a sample of a patient with kidney cancer; amplifying the DNA test sample using the kit; and determining whether or not there is a gender-specific marker from the results of amplification.

Advantageous Effects

[0014] Because there is a relationship between the gender of a patient with kidney cancer and a mutation of a gene selected from a gene group consisting of ACSS3, ADAM21, AFF2, ALG13, BAP1, BRWD3, COL4A5, CPEB1, ERBB2, HSP90AA1, IRAK1, KDMSC, KDM6A, LRP12, NCOA6, NHS, RGAG1, SCAF1, SH3TC1, TBC1D8B, TET2, TEX13A, ULK3, WNK3, ARSF, CFP, FAM47A, PHF16, ZNF449, and SCRN1, all genes of which are found in the present invention, the presence of the mutation of the gene can be checked to predict a difference in therapeutic effect against kidney cancer and a difference in survival rate of the patient with kidney cancer according to the gender of the patient with kidney cancer.

[0015] In addition, because there is a relationship between a survival rate of the patient with kidney cancer who has a certain gender and a mutation of one gene selected from a gene group consisting of ACSS3, ALG13, ARSF, CFP, FAM47A, KDM6A, PHF16, ZNF449, and SCRN1, all genes of which are found in the present invention, or a relationship between the mutation of the gene and a relapse rate of kidney cancer, mutations of the genes according to the present invention can be used as the marker to predict the prognosis of the patient with kidney cancer.

[0016] However, the effects of the present invention are not limited to the effects as described above, and other effects not disclosed herein will be clearly understood from the following detailed description by those skilled in the art.

DESCRIPTION OF DRAWINGS

[0017] FIG. 1 is a diagram showing gender-specific mutant genes specifically shown from candidate genes when patients with kidney cancer who are classified according to the gender thereof are compared with each other. Each of numerical values represents the number of the patients with kidney cancer in which mutated genes are identified.

[0018] FIGS. 2 to 10 are graphs plotted for an overall survival rate or a disease-free survival rate of patients with kidney cancer (red) who have mutations in respective ACSS3, ALG13, ARSF, CFP, FAM47A, KDM6A, PHF16, ZNF449, and SCRN1 genes and patients with kidney cancer (blue) who have no mutations in the corresponding genes.

BEST MODE

[0019] Unless defined otherwise in this specification, all the technical and scientific terms used herein have the same meanings as what are generally understood by a person skilled in the related art to which the present invention belongs. In general, the nomenclatures used in this specification and the experimental methods described below are widely known and generally used in the related art.

[0020] Hereinafter, the present invention will be described in detail.

[0021] 1. Gender-Specific Mutant Genes in Patient with Kidney Cancer and Primer Sets Capable of Detecting the Mutant Genes

[0022] One aspect of the present invention provides a kit for providing information required to predict a difference in therapeutic effect against kidney cancer or diagnose prognosis of a patient with kidney cancer according to the gender of the patient with kidney cancer, wherein the kit may detect a gender-specific marker that is a mutation of at least one gene selected from a gene group consisting of ACSS3 (Gene Bank Accession Number: NM_024560.3), ADAM21 (Gene Bank Accession Number: NM_003813.3), AFF2 (Gene Bank Accession Number: NM_002025.3), ALG13 (Gene Bank Accession Number: NM_001099922.2), ARSF (Gene Bank Accession Number: NM_001201538.1), BAP1 (Gene Bank Accession Number: NM_004656.3), BRWD3 (Gene Bank Accession Number: NM_153252.4), CFP (Gene Bank Accession Number: NM_001145252.1), COL4A5 (Gene Bank Accession Number: NM_000495.4), CPEB1 (Gene Bank Accession Number: NM_030594.4), ERBB2 (Gene Bank Accession Number: NM_004448.3), FAM47A (Gene Bank Accession Number: NM_203408.3), HSP90AA1 (Gene Bank Accession Number: NM_001017963.2), IRAK1 (Gene Bank Accession Number: NM_001569.3), KDMSC (Gene Bank Accession Number: NM_004187.3), KDM6A (Gene Bank Accession Number: NM_021140.3), LRP12 (Gene Bank Accession Number: NM_013437.4), NCOA6 (Gene Bank Accession Number: NM_001242539.2), NHS (Gene Bank Accession Number: NM_198270.3), PHF16(JADE3) (Gene Bank Accession Number: NM_001077445.2), RGAG1 (Gene Bank Accession Number: NM_020769.2), SCAF1 (Gene Bank Accession Number: NM_021228.2), SCRN1 (Gene Bank Accession Number: NM_001145514.1), SH3TC1 (Gene Bank Accession Number: NM_018986.4), TBC1D8B (Gene Bank Accession Number: NM_017752.2), TET2 (Gene Bank Accession Number: NM_001127208.2), TEX13A (Gene Bank Accession Number: NM_001291277.1), ULK3 (Gene Bank Accession Number: NM_001099436.3), WNK3 (Gene Bank Accession Number: NM_001002838.3), and ZNF449 (Gene Bank Accession Number: NM_152695.5).

[0023] The full names of abbreviations for the genes may be ACSS3 (Homo sapiens acyl-CoA synthetase short chain family member 3), ADAM21 (Homo sapiens ADAM metallopeptidase domain 21), AFF2 (Homo sapiens AF4/FMR2 family member 2), ALG13 (UDP-N-acetylglucosaminyltransferase subunit), BAP1 (BRCA1-associated protein 1), BRWD3 (bromodomain and WD repeat domain containing 3), COL4A5 (collagen type IV alpha 5 chain), CPEB1 (cytoplasmic polyadenylation element binding protein 1), ERBB2 (erb-b2 receptor tyrosine kinase 2), HSP90AA1 (heat shock protein 90 alpha family class A member 1), IRAK1 (interleukin 1 receptor associated kinase 1), KDMSC (lysine demethylase 5C), KDM6A (lysine demethylase 6A), LRP12 (LDL receptor related protein 12), NCOA6 (nuclear receptor coactivator 6), NHS (NHS actin remodeling regulator), RGAG1 (retrotransposon Gag like 9), SCAF1 (SR-related CTD associated factor 1), SH3TC1 (SH3 domain and tetratricopeptide repeats 1), TBC1D8B (TBC1 domain family member 8B), TET2 (tet methylcytosine dioxygenase 2), TEX13A (testis-expressed 13A), ULK3 (unc-51 like kinase 3), WNK3 (WNK lysine-deficient protein kinase 3), ARSF (arylsulfatase F), CFP (complement factor properdin), FAM47A (family with sequence similarity 47 member A), PHF16 (jade family PHD finger 3), ZNF449 (zinc finger protein 449), and SCRN1 (secernin 1).

[0024] According to one exemplary embodiment of the present invention, there is provided a kit for providing information required to predict a difference in therapeutic effect against kidney cancer or diagnose prognosis of a patient with kidney cancer according to the gender of the patient with kidney cancer, wherein the kit may detect a mutation of at least one gene selected from the following genes: a mutation of a gene coding for at least one selected from the group consisting of ACSS3, ADAM21, AFF2, ALG13, BAP1, BRWD3, COL4A5, CPEB1, ERBB2, HSP90AA1, IRAK1, KDMSC, KDM6A, LRP12, NCOA6, NHS, RGAG1, SCAF1, SH3TC1, TBC1D8B, TET2, TEX13A, ULK3, WNK3, ARSF, CFP, FAM47A, PHF16, ZNF449, and SCRN1.

[0025] In the present invention, the term `diagnosis` refers to a process in which the presence or nature of a pathologic status is determined, that is, a process in which a difference in therapeutic effect against cancer according to the gender of a cancer patient is verified for the objects of the present invention and a process in which the relapse and metastasis of cancer, drug response and resistance, and the like in the corresponding subject after cancer treatment are judged. Preferably, when the mutations of the genes of the present invention are used, it is also possible to predict a difference in survival rate by checking whether there are mutations in a test sample of a patient with kidney cancer. In this case, a difference in therapeutic effect against kidney cancer and the prognosis of the corresponding patient in the future according to the gender of the corresponding patient with kidney cancer may be determined from the difference in survival rate.

[0026] In the present invention, the term `prognosis` refers to the prediction of the progress and cure of a disease having a probability of cancer-attributable death or progression, including, for example, the relapse and metastatic spread of a neoplastic disease such as cancer, and drug resistance. The prognosis may refer to a prediction of the prognosis of kidney cancer for the objects of the present invention. Preferably, the prognosis may refer to a prediction of a disease-free survival rate or survival rate of the patient with kidney cancer.

[0027] In the present invention, the term `cancer` includes any members belonging to a class of diseases characterized by the uncontrolled growth of abnormal cells. The term includes all stages and grades of cancers, including all types of known cancers and neoplastic conditions, cancers before/after metastasis, regardless whether the cancer is characterized by any one malignant, benign, soft tissue, or solid cancer.

[0028] In the present invention, the term `gene` and modified products thereof include DNA fragments associated with the synthesis of polypeptide chains; each of the DNA fragments includes regions upstream and downstream from a coding region, for example, a promoter and a 3'-untranslated region, respectively, and also includes intervening sequences (introns) between respective coding fragments (exons).

[0029] The mutation of the gene may include any one or more mutations, and may, for example, have at least one mutation selected from the group consisting of truncating mutation, missense mutation, nonsense mutation, frameshift mutation, in-frame mutation, splice mutation, and splice_region mutation. The frameshift mutation may be at least one selected from a frameshift insertion (FS ins) mutation and a frameshift deletion (FS del) mutation. The in-frame mutation may be at least one selected from an in-frame insertion (IF ins) mutation and an in-frame deletion (IF del) mutation.

[0030] In conjunction with mutations in a polypeptide sequence, the term "X#Y" is obviously recognized in the related art. Here, the sign "#" represents a mutation position with respect to the amino acid number of a polypeptide, "X" represents an amino acid found at the position of a wild-type amino acid sequence, and "Y" represents a mutant amino acid found at the same position. For example, the sign "G1717V" with respect to a BAZ2B polypeptide means that there is a glycine residue at amino acid number 1,717 of a wild-type BAZ2B sequence, and the glycine residue is replaced with valine in a mutant BAZ2B sequence.

[0031] The mutations of the genes are as follows:

[0032] The mutation of the gene coding for ACSS3 is a nonsense mutation `R634*`, a splice mutation A152_splice' (where T is substituted with C at position 81503485 on the chromosome), or a missense mutation `G268D`, wherein the sign in a notation of the nonsense mutation means that the synthesis of amino acids is terminated at the corresponding amino acid position (a description thereof is omitted hereinafter), in an amino acid sequence set forth in SEQ ID NO: 1; the mutation of the gene coding for ADAM21 is at least one mutation selected from the group consisting of N265Y, R408C, T589S, and I161V in an amino acid sequence set forth in SEQ ID NO: 2; the mutation of the gene coding for AFF2 is at least one missense mutation selected from the group consisting of S770F, P513H, T640N, and 1149K in an amino acid sequence set forth in SEQ ID NO: 3; the mutation of the gene coding for ALG13 is at least one missense mutation selected from P925T and V456E, or a frameshift deletion (FS del) mutation `L195Pfs*23`, where a notation of the frameshift mutation is based on the amino acid type (an amino acid position) and the amino acid type fs* (the number of nucleotides downstream from the amino acid position to a stop codon) (both the FS ins mutation and FS del mutation are denoted by the same notation, and a description thereof is omitted hereinafter), in an amino acid sequence set forth in SEQ ID NO: 4; the mutation of the gene coding for BAP1 is a nonstart mutation `M1?` (where T is substituted with C at position 52443894 and C is substituted with T at position 52443892 on the chromosome), at least one nonsense mutation selected from the group consisting of G128*, E402*, Q253*, Q267*, S460*, Y627*, S279*, R60*, Q40*, Q156*, and K626*, at least one FS del mutation selected from the group consisting of E283Gfs*52, V335Efs*56, K711Sfs*25, R700Gfs*36, D74Efs*4, and D407Vfs*23, at least one missense mutation selected from the group consisting of F170V, F170C, E31A, N78S, L49V, D75G, SlOT, N229H, G109V, L17P, A145G, and A1061T, at least one splice mutation selected from the group consisting of X23_splice (where C is substituted with T at position 52443729 on the chromosome), X41_splice (where A is substituted with G at position 52443568 on the chromosome), X41_splice (where A is substituted with T at position 52443568 on the chromosome), X23_splice (where ACCTGCGATGAGGAAAGGAAAGCAG at positions 52443623 to 52443647 are deleted from the chromosome), and X311_splice (where C is substituted with A at position 52439311 on the chromosome), or an in-frame deletion (IF del) mutation `K659del`, where the sign `del` in a notation of the IF del mutation represents a deletion of the corresponding amino acid at the corresponding amino acid position (a description thereof is omitted hereinafter), in an amino acid sequence set forth in SEQ ID NO: 5; the mutation of the gene coding for BRWD3 is at least one missense mutation selected from G287A and I1747N in an amino acid sequence set forth in SEQ ID NO: 6; the mutation of the gene coding for COL4A5 is at least one missense mutation selected from the group consisting of P1184L, P756S, P1365S, G1427V, and A1656T, or a splice mutation `X1510_splice` (where G is substituted with T at position 107935977 on the chromosome) in an amino acid sequence set forth in SEQ ID NO: 7; the mutation of the gene coding for CPEB1 is at least one missense mutation selected from S393R and G136V, or a splice mutation `X499_splice` (where C is substituted with A at position 83215272 on the chromosome) in an amino acid sequence set forth in SEQ ID NO: 8; the mutation of the gene coding for ERBB2 is at least one missense mutation selected from the group consisting of E1114G, S649T, and V2191, or an FS ins mutation `N388Qfs*14` in an amino acid sequence set forth in SEQ ID NO: 9; the mutation of the gene coding for HSP90AA1 is at least one missense mutation selected from the group consisting of D512N, H806R, I325T, and L167V in an amino acid sequence set forth in SEQ ID NO: 10; the mutation of the gene coding for IRAK1 is a nonsense mutation `Q280*`, or at least one missense mutation selected from V548M and Q584K in an amino acid sequence set forth in SEQ ID NO: 11; the mutation of the gene coding for KDMSC is at least one nonsense mutation selected from the group consisting of R681*, Q813*, E284*, E798*, Y639*, S1110*, K459*, and R215*, at least one missense mutation selected from the group consisting of E1152K, R1458W, G536W, C730R, E592V, C512W, C730F, and H733P, a splice mutation `X321_splice` (where A is substituted with G at position 53244975 on the chromosome), or at least one FS del mutation selected from the group consisting of T471Vfs*5, Q1427Pfs*50, E122Vfs*14, E1131Sfs*16, H988Tfs*18, P27Lfs*46, F56Cfs*18, D1414Efs*54, and G845Rfs*2 in an amino acid sequence set forth in SEQ ID NO: 12; the mutation of the gene coding for KDM6A is a missense mutation `A30V`, an FS mutation `A1246Pfs*19`, or an IF del mutation `V156del` in an amino acid sequence set forth in SEQ ID NO: 13; the mutation of the gene coding for LRP12 is at least one missense mutation selected from the group consisting of S622L, E639K, and V6711 in an amino acid sequence set forth in SEQ ID NO: 14; the mutation of the gene coding for NCOA6 is at least one missense mutation selected from the group consisting of G164E, N8771, N864Y, and V1444A, or an FS ins mutation `H832Sfs*47` in an amino acid sequence set forth in SEQ ID NO: 15; the mutation of the gene coding for NHS is at least one missense mutation selected from the group consisting of C360R, P1107A, and D1069H in an amino acid sequence set forth in SEQ ID NO: 16; the mutation of the gene coding for RGAG1 is at least one missense mutation selected from the group consisting of A1015G, M858V, and G1053R in an amino acid sequence set forth in SEQ ID NO: 17; the mutation of the gene coding for SCAF1 is at least one FS ins mutation selected from the group consisting of A219Sfs*11, P211Tfs*19, P211Tfs*19, and A216Pfs*94, or an FS del mutation `A216Pfs*94` in an amino acid sequence set forth in SEQ ID NO: 18; the mutation of the gene coding for SH3TC1 is at least one missense mutation selected from A375V and L180F or an FS del mutation `R2238Sfs*38` in an amino acid sequence set forth in SEQ ID NO: 19; the mutation of the gene coding for TBC1D8B is at least one missense mutation selected from the group consisting of G1059V, A614T, and Y815F, or a nonsense mutation `S861*` in an amino acid sequence set forth in SEQ ID NO: 20; the mutation of the gene coding for TET2 is at least one missense mutation selected from the group consisting of Q317K, L757V, V449E, N1714K, D194E, N1390H, R1451Q, M600I, and P554S, or a nonsense mutation `1(326*` in an amino acid sequence set forth in SEQ ID NO: 21; the mutation of the gene coding for TEX13A is at least one missense mutation selected from R393S and Y257D, or a splice mutation `X199_splice` (where C at position 104464282 is deleted from the chromosome) in an amino acid sequence set forth in SEQ ID NO: 22; the mutation of the gene coding for ULK3 is an FS del mutation `Q81Sfs*41` and at least one missense mutation selected from D79H and L77V in an amino acid sequence set forth in SEQ ID NO: 23; the mutation of the gene coding for WNK3 is at least one nonsense mutation selected from S865* and Y589* and a missense mutation `E537G` in an amino acid sequence set forth in SEQ ID NO: 24; the mutation of the gene coding for ARSF is a missense mutation `I42F` in an amino acid sequence set forth in SEQ ID NO: 25; the mutation of the gene coding for CFP is at least one missense mutation selected from the group consisting of S27L, R359Q, and E135K, or an FS ins mutation `E323Gfs*34` in an amino acid sequence set forth in SEQ ID NO: 26; the mutation of the gene coding for FAM47A is at least one missense mutation selected from R505H and E507Q, or at least one IF del mutation selected from L235_H246del and L235_H246del in an amino acid sequence set forth in SEQ ID NO: 27; the mutation of the gene coding for PHF16 is at least one missense mutation selected from K656Q and R207W in an amino acid sequence set forth in SEQ ID NO: 28; the mutation of the gene coding for ZNF449 is a missense mutation `F183I` in an amino acid sequence set forth in SEQ ID NO: 29; and the mutation of the gene coding for SCRN1 is a missense mutation `D427Y` or an FS ins mutation `A257Cfs*34` in an amino acid sequence set forth in SEQ ID NO: 30.

[0033] An analytical method for diagnosing the prognosis of kidney cancer using the mutation of the gene, a next-generation sequencing (NGS) method, RT-PCR, a direct nucleic acid sequencing method, a microarray, and the like may be used. In this case, any methods may be used without limitation as long as the methods can be used to determine the presence of mutations using the mutation of the gene according to the present invention. According to one exemplary embodiment, the presence of mutations is determined using an anti-antibody (a mutant antibody against each gene) or nucleic acid probe that hybridizes with a mutant polynucleotide of each of the gene under a stringent condition. According to another exemplary embodiment, the anti-antibody or nucleic acid probe is detectably labeled. According to still another exemplary embodiment, a label is selected from the group consisting of an immunofluorescent label, a chemiluminescent label, a phosphorescent label, an enzyme label, a radioactive label, avidin/biotin, colloidal gold particles, coloring particles, and magnetic particles. According to yet another exemplary embodiment, the presence of mutations is determined using an radioimmunoassay, a Western blot assay, an immunofluorescence assay, an enzyme immunoassay, an immunoprecipitation assay, a chemiluminescence assay, an immunohistochemical assay, a dot-blot assay, a slot-blot assay, or a flow cytometric assay. According to yet another exemplary embodiment, the presence of mutations is determined by RT-PCR. According to yet another exemplary embodiment, the presence of mutations is determined by nucleic acid sequencing.

[0034] In the present invention, the term `polynucleotide` generally refers to any polyribonucleotide or polydeoxyribonucleotide that may be unmodified RNA or DNA or modified RNA or DNA. Therefore, non-limiting examples of the polynucleotide as defined herein include single- and double-stranded DNAs, DNAs including single- and double-stranded regions, single- and double-stranded RNAs, and RNAs including single- and double-stranded regions, and hybrid molecules including DNAs and RNAs that may be single-stranded or more typically double-stranded or may include single- and double-stranded regions. Therefore, the DNA or RNA having a modified backbone due to its stability or other reasons is a `polynucleotide` as described in the terms intended herein. Also, the DNA or RNA containing unusual bases such as inosine or modified bases such as a tritiated base is encompassed in the term `polynucleotide` as defined herein. Generally, the term `polynucleotide` includes all chemically, enzymatically and/or metabolically modified forms of an unmodified polynucleotide. The polynucleotide may be prepared by various methods including an in vitro recombinant DNA-mediated technology, and prepared by expression of DNA in cells and organisms.

[0035] Primer sets capable of detecting the mutation of the gene, that is, primer sets for diagnosing prognosis of kidney cancer are as follows: at least one primer set selected from the group consisting of base sequence pairs set forth in SEQ ID NO: 31 and SEQ ID NO: 32, SEQ ID NO: 33 and SEQ ID NO: 34, and SEQ ID NO: 35 and SEQ ID NO: 36 to detect the mutation of ACSS3; at least one primer set selected from the group consisting of base sequence pairs set forth in SEQ ID NO: 37 and SEQ ID NO: 38, SEQ ID NO: 39 and SEQ ID NO: 40, SEQ ID NO: 41 and SEQ ID NO: 42, and SEQ ID NO: 43 and SEQ ID NO: 44 to detect the mutation of ADAM21; at least one primer set selected from the group consisting of base sequence pairs set forth in SEQ ID NO: 45 and SEQ ID NO: 46, SEQ ID NO: 47 and SEQ ID NO: 48, SEQ ID NO: 49 and SEQ ID NO: 50, and SEQ ID NO: 51 and SEQ ID NO: 52 to detect the mutation of AFF2; at least one primer set selected from the group consisting of base sequence pairs set forth in SEQ ID NO: 53 and SEQ ID NO: 54, SEQ ID NO: 55 and SEQ ID NO: 56, and SEQ ID NO: 57 and SEQ ID NO: 58 to detect the mutation of ALG13; at least one primer set selected from the group consisting of base sequence pairs set forth in SEQ ID NO: 59 and SEQ ID NO: 60, SEQ ID NO: 61 and SEQ ID NO: 62, SEQ ID NO: 63 and SEQ ID NO: 64, SEQ ID NO: 65 and SEQ ID NO: 66, SEQ ID NO: 67 and SEQ ID NO: 68, SEQ ID NO: 69 and SEQ ID NO: 70, SEQ ID NO: 71 and SEQ ID NO: 72, SEQ ID NO: 73 and SEQ ID NO: 74, SEQ ID NO: 75 and SEQ ID NO: 76, SEQ ID NO: 77 and SEQ ID NO: 78, SEQ ID NO: 79 and SEQ ID NO: 80, SEQ ID NO: 81 and SEQ ID NO: 82, SEQ ID NO: 83 and SEQ ID NO: 84, SEQ ID NO: 85 and SEQ ID NO: 86, SEQ ID NO: 87 and SEQ ID NO: 88, SEQ ID NO: 89 and SEQ ID NO: 90, SEQ ID NO: 91 and SEQ ID NO: 92, and SEQ ID NO: 93 and SEQ ID NO: 94 to detect the mutation of BAP1; at least one primer set selected from base sequence pairs set forth in SEQ ID NO: 95 and SEQ ID NO: 96, and SEQ ID NO: 97 and SEQ ID NO: 98 to detect the mutation of BRWD3; at least one primer set selected from the group consisting of base sequence pairs set forth in SEQ ID NO: 99 and SEQ ID NO: 100, SEQ ID NO: 101 and SEQ ID NO: 102, SEQ ID NO: 103 and SEQ ID NO: 104, SEQ ID NO: 105 and SEQ ID NO: 106, SEQ ID NO: 107 and SEQ ID NO: 108, and SEQ ID NO: 109 and SEQ ID NO: 110 to detect the mutation of COL4A5; at least one primer set selected from the group consisting of base sequence pairs set forth in SEQ ID NO: 111 and SEQ ID NO: 112, SEQ ID NO: 113 and SEQ ID NO: 114, and SEQ ID NO: 115 and SEQ ID NO: 116 to detect the mutation of CPEB1; at least one primer set selected from the group consisting of base sequence pairs set forth in SEQ ID NO: 117 and SEQ ID NO: 118, SEQ ID NO: 119 and SEQ ID NO: 120, and SEQ ID NO: 121 and SEQ ID NO: 122 to detect the mutation of ERBB2; at least one primer set selected from the group consisting of base sequence pairs set forth in SEQ ID NO: 123 and SEQ ID NO: 124, SEQ ID NO: 125 and SEQ ID NO: 126, SEQ ID NO: 127 and SEQ ID NO: 128, and SEQ ID NO: 129 and SEQ ID NO: 130 to detect the mutation of HSP90AA1; at least one primer set selected from base sequence pairs set forth in SEQ ID NO: 131 and SEQ ID NO: 132, and SEQ ID NO: 133 and SEQ ID NO: 134 to detect the mutation of IRAK1; at least one primer set selected from the group consisting of base sequence pairs set forth in SEQ ID NO: 135 and SEQ ID NO: 136, SEQ ID NO: 137 and SEQ ID NO: 138, SEQ ID NO: 139 and SEQ ID NO: 140, SEQ ID NO: 141 and SEQ ID NO: 142, SEQ ID NO: 143 and SEQ ID NO: 144, SEQ ID NO: 145 and SEQ ID NO: 146, SEQ ID NO: 147 and SEQ ID NO: 148, SEQ ID NO: 149 and SEQ ID NO: 150, SEQ ID NO: 151 and SEQ ID NO: 152, SEQ ID NO: 153 and SEQ ID NO: 154, SEQ ID NO: 155 and SEQ ID NO: 156, SEQ ID NO: 157 and SEQ ID NO: 158, SEQ ID NO: 159 and SEQ ID NO: 160, SEQ ID NO: 161 and SEQ ID NO: 162, SEQ ID NO: 163 and SEQ ID NO: 164, SEQ ID NO: 165 and SEQ ID NO: 166, SEQ ID NO: 167 and SEQ ID NO: 168, SEQ ID NO: 169 and SEQ ID NO: 170, SEQ ID NO: 171 and SEQ ID NO: 172, SEQ ID NO: 173 and SEQ ID NO: 174, and SEQ ID NO: 175 and SEQ ID NO: 176 to detect the mutation of KDMSC; at least one primer set selected from base sequence pairs set forth in SEQ ID NO: 177 and SEQ ID NO: 178, and SEQ ID NO: 179 and SEQ ID NO: 180 to detect the mutation of KDM6A; at least one primer set selected from base sequence pairs set forth in SEQ ID NO: 181 and SEQ ID NO: 182, and SEQ ID NO: 183 and SEQ ID NO: 184 to detect the mutation of LRP12; at least one primer set selected from the group consisting of base sequence pairs set forth in SEQ ID NO: 185 and SEQ ID NO: 186, SEQ ID NO: 187 and SEQ ID NO: 188, SEQ ID NO: 189 and SEQ ID NO: 190, and SEQ ID NO: 191 and SEQ ID NO: 192 to detect the mutation of NCOA6; at least one primer set selected from the group consisting of base sequence pairs set forth in SEQ ID NO: 193 and SEQ ID NO: 194, SEQ ID NO: 195 and SEQ ID NO: 196, and SEQ ID NO: 197 and SEQ ID NO: 198 to detect the mutation of NHS; at least one primer set selected from the group consisting of base sequence pairs set forth in SEQ ID NO: 199 and SEQ ID NO: 200, SEQ ID NO: 201 and SEQ ID NO: 202, and SEQ ID NO: 203 and SEQ ID NO: 204 to detect the mutation of RGAG1; at least one primer set selected from the group consisting of base sequence pairs set forth in SEQ ID NO: 205 and SEQ ID NO: 206, SEQ ID NO: 207 and SEQ ID NO: 208, SEQ ID NO: 209 and SEQ ID NO: 210, SEQ ID NO: 211 and SEQ ID NO: 212, and SEQ ID NO: 213 and SEQ ID NO: 214 to detect the mutation of SCAF1; at least one primer set selected from the group consisting of base sequence pairs set forth in SEQ ID NO: 215 and SEQ ID NO: 216, SEQ ID NO: 217 and SEQ ID NO: 218, and SEQ ID NO: 219 and SEQ ID NO: 220 to detect the mutation of SH3TC1; at least one primer set selected from the group consisting of base sequence pairs set forth in SEQ ID NO: 221 and SEQ ID NO: 222, SEQ ID NO: 223 and SEQ ID NO: 224, SEQ ID NO: 225 and SEQ ID NO: 226, and SEQ ID NO: 227 and SEQ ID NO: 228 to detect the mutation of TBC1D8B; at least one primer set selected from the group consisting of base sequence pairs set forth in SEQ ID NO: 229 and SEQ ID NO: 230, SEQ ID NO: 231 and SEQ ID NO: 232, SEQ ID NO: 233 and SEQ ID NO: 234, SEQ ID NO: 235 and SEQ ID NO: 236, SEQ ID NO: 237 and SEQ ID NO: 238, SEQ ID NO: 239 and SEQ ID NO: 240, SEQ ID NO: 241 and SEQ ID NO: 242, SEQ ID NO: 243 and SEQ ID NO: 244, and SEQ ID NO: 245 and SEQ ID NO: 246 to detect the mutation of TET2; at least one primer set selected from the group consisting of base sequence pairs set forth in SEQ ID NO: 247 and SEQ ID NO: 248, SEQ ID NO: 249 and SEQ ID NO: 250, and SEQ ID NO: 251 and SEQ ID NO: 252 to detect the mutation of TEX13A; a primer set consisting of base sequence pairs set forth in SEQ ID NO: 253 and SEQ ID NO: 254 to detect the mutation of ULK3; at least one primer set selected from the group consisting of base sequence pairs set forth in SEQ ID NO: 255 and SEQ ID NO: 256, SEQ ID NO: 257 and SEQ ID NO: 258, and SEQ ID NO: 259 and SEQ ID NO: 260 to detect the mutation of WNK3; a primer set consisting of base sequence pairs set forth in SEQ ID NO: 261 and SEQ ID NO: 262 to detect the mutation of ARSF; at least one primer set selected from the group consisting of base sequence pairs set forth in SEQ ID NO: 263 and SEQ ID NO: 264, SEQ ID NO: 265 and SEQ ID NO: 266, SEQ ID NO: 267 and SEQ ID NO: 268, and SEQ ID NO: 269 and SEQ ID NO: 270 to detect the mutation of CFP; a primer set consisting of base sequence pairs set forth in SEQ ID NO: 271 and SEQ ID NO: 272 to detect the mutation of FAM47A; at least one primer set selected from the group consisting of base sequence pairs set forth in SEQ ID NO: 273 and SEQ ID NO: 274, and SEQ ID NO: 275 and SEQ ID NO: 276 to detect the mutation of PHF16; a primer set consisting of base sequence pairs set forth in SEQ ID NO: 277 and SEQ ID NO: 278 to detect the mutation of ZNF449; and at least one primer set selected from base sequence pairs set forth in SEQ ID NO: 279 and SEQ ID NO: 280, and SEQ ID NO: 281 and SEQ ID NO: 282 to detect the mutation of SCRN1.

[0036] The kit of the present invention thus manufactured is very economical because a lot of time and cost may be save, compared to typical gene mutation search methods known in the art. Several days or Several months are averagely taken to search for one gene thoroughly using the conventional gene mutation search methods such as single strand conformational polymorphism (SSCP), a protein truncation test (PTT), cloning, direct sequencing, and the like. Also, the gene mutation may be rapidly and simply examined accurately using the next-generation sequencing (NGS) method. When the mutation is checked using conventional analytical methods such as SSCP, cloning, direct sequencing, restriction fragment length polymorphism (RFLP), and the like, approximately one month is taken to complete the check. On the other hand, when the kit of the present invention is used and a DNA test sample is prepared, results may be obtained within approximately 10 to 11 hours. Because a primer set capable of detecting the mutation of the gene is stacked in one chip, the time and cost may be saved compared to the conventional methods. Because less than half the reagents' cost per experiment is averagely consumed compared to the conventional methods, a higher cost saving effect may be expected in consideration of the researchers' labor costs.

[0037] 2. Method of Providing Information Required to Diagnose Prognosis of Kidney Cancer Using Survival-Specific Mutant Gene

[0038] According to another aspect of the present invention, there is provided a method of providing information required to verify a difference in therapeutic effect against kidney cancer according to the gender of a patient with kidney cancer. Here, the method includes preparing a DNA test sample from a sample of a patient with kidney cancer whose gender is identified; amplifying the DNA test sample using the kit; determining whether or not there is a gender-specific marker specific to a gender group of target patients from the results of amplification; treating the patient with kidney cancer, in which the gender-specific marker is identified, with any candidate material for treating kidney cancer or healing the patient with kidney cancer using any method; and choosing any candidate material for treating kidney cancer or any method of treating kidney cancer as a therapeutic candidate material or a therapeutic method, which is suitable for the gender group of patients with kidney cancer in which the gender-specific marker is identified, when the any candidate material or the any method is used to treat kidney cancer.

[0039] According to still another aspect of the present invention, there is provided a method of providing information required to diagnose prognosis of kidney cancer according to the gender of a patient with kidney cancer. Here, the method includes preparing a DNA test sample from a sample of a patient with kidney cancer; amplifying the DNA test sample using the kit; and determining whether or not there is a gender-specific marker from the results of amplification.

[0040] The `kit for diagnosing prognosis of kidney cancer` is as described in `1. gender-specific mutant genes in patient with kidney cancer and primer sets capable of detecting the mutant genes`, and thus a specific description thereof is omitted.

[0041] The any candidate material for treating kidney cancer may be a therapeutic agent generally used to treat kidney cancer, or a novel material whose therapeutic effect against kidney cancer is not known, but the present invention is not limited thereto. It may be determined whether or not the any therapeutic candidate material has a therapeutic effect on a certain group of patients by treating a patient with kidney cancer having a gender-specific marker with the therapeutic candidate material to check the therapeutic effect. When the therapeutic candidate material has a therapeutic effect against kidney cancer, it may be predicted that the therapeutic candidate material has a high therapeutic effect when the therapeutic candidate material is applied to a group of patients having the same gender-specific marker, thereby providing useful information to determine a therapeutic strategy. Also, when a therapeutic effect is not exerted by the use of the any therapeutic candidate material, the unnecessary treatment needs not to be performed by suspending the therapy on the group of patients having the same gender-specific marker. Therefore, a therapeutic strategy may be effectively designed.

[0042] Any method of treating kidney cancer may also be applied instead of the any therapeutic candidate material. After verifying a therapeutic effect in a group of patients having a certain gender-specific marker, it may be determined whether or not the method is applied to the group of patients having the same gender-specific marker. When the therapeutic effect is verified in the group of patients having the gender-specific marker, the any therapeutic candidate material and the any method of treating kidney cancer may be used together.

[0043] The term `sample` used herein includes any biological specimen obtained from a patient. The sample includes whole blood, plasma, serum, red blood cells, white blood cells (for example, peripheral blood mononuclear cells), a ductal fluid, hydrops abdominis, a pleural efflux, a nipple aspirate, a lymph fluid (for example, disseminated tumor cells of lymph nodes), a bone marrow aspirate, saliva, urine, feces (that is, stool), phlegm, a bronchial lavage fluid, tear, a fine needle aspirate (for example, collected by random mammary fine needle aspiration), any other bodily fluids, a tissue sample (for example, a tumor tissue), for example, a tumor biopsy (for example, an aspiration biopsy) or a lymph node (for example, a sentinel lymph node biopsy), a tissue sample (for example, a tumor tissue), for example, a surgical resection of tumor, and cell extracts thereof. In some embodiments, the sample is whole blood or some components thereof, for example, plasma, serum or cell pellets. In another embodiment, the sample is obtained by isolating circulating cells of a solid tumor from the whole blood or cell fractions thereof using any techniques known in the related art. In still another embodiment, the sample is, for example, a formalin-fixed paraffin-embedded (FFPE) tumor tissue sample from a solid tumor such as colon cancer.

[0044] In certain embodiments, the sample is a tumor lysate or extract prepared from a frozen tissue obtained from a target having colon cancer.

[0045] The term `patient` generally includes a human, and may also include other animals, for example, other primates, rodents, dogs, cats, horses, sheep, pigs, and the like.

[0046] The term `subject` includes targets excluding a human, which are diagnosed with kidney cancer or suspected to have kidney cancer.

[0047] The method may be used to predict an overall survival rate or disease-free survival rate of the patient with kidney cancer.

[0048] In the present invention, the term `overall survival rate` includes clinical endpoints recorded for patients who are diagnosed with a disease, for example, cancer or alive for a predetermined period after treatment of the disease, and refers to a survival probability of the patients regardless of the relapse of cancer.

[0049] In the present invention, the term `disease-free survival rate (DFS)` includes a survival period of a patient without the relapse of cancer after treatment of a certain disease (for example, cancer).

[0050] According to the present invention, the presence of mutations of the gene of the present invention in a sample of a patient with kidney cancer may be analyzed to verify what the prognosis of a subject having a target test sample is for cancer. Also, such a method may be established by comparing overall survival rates or disease-free survival rates of control subjects who are known to have a good prognosis and have no mutations. In the present invention, the subject known to have a good prognosis refers to a subject who has no family histories such as metastasis, relapse, death, and the like after the onset of cancer.

[0051] The sample of the subject suspected to have cancer refers to a test sample of a subject or a tissue which already develops cancer or tumor or is expected to develop cancer or tumor, that is, a target test sample used to diagnose the prognosis of cancer or tumor.

[0052] The gender-specific marker may be a mutation of a gene coding for one selected from the group consisting of ACSS3, ADAM21, AFF2, ALG13, BAP1, BRWD3, COL4A5, CPEB1, ERBB2, HSP90AA1, IRAK1, KDMSC, KDM6A, LRP12, NCOA6, NHS, RGAG1, SCAF1, SH3TC1, TBC1D8B, TET2, TEX13A, ULK3, WNK3, ARSF, CFP, FAM47A, PHF16, ZNF449, and SCRN1. In females of the patients with kidney cancer, the gender-specific marker may be a mutation of a gene coding for one selected from the group consisting of ACSS3, ADAM21, AFF2, ALG13, BAP1, BRWD3, COL4A5, CPEB1, ERBB2, HSP90AA1, IRAK1, KDMSC, KDM6A, LRP12, NCOA6, NHS, RGAG1, SCAF1, SH3TC1, TBC1D8B, TEX13A, ULK3, WNK3, ARSF, CFP, FAM47A, PHF16, ZNF449, and SCRN1. In males of the patients with kidney cancer, the gender-specific marker may be a mutation of a gene coding for TET2.

[0053] The method of providing information required to diagnose the prognosis of kidney cancer according to the gender of the patient with kidney cancer may be used to predict the overall survival rate or disease-free survival rate of the patient with kidney cancer. For example, the method may further include judging that the survival rate of the patient with kidney cancer is not good or that a relapse rate of kidney cancer in the patient with kidney cancer is high when the mutation is identified in the gene coding for one selected from the group consisting of ACSS3, ALG13, ARSF, CFP, FAM47A, KDM6A, PHF16, ZNF449, and SCRN1, and the patient with kidney cancer is female.

[0054] The method of providing information required to diagnose the prognosis of kidney cancer according to the gender of the patient with kidney cancer may further include judging that the survival rate of the patient with kidney cancer is not good when the gender of the patient with kidney cancer is female and the mutation is identified in the gene coding for one selected from the group consisting of ACSS3, ALG13, ARSF, CFP, FAM47A, KDM6A, PHF16, and ZNF449, and the patient with kidney cancer is male.

[0055] The method of providing information required to diagnose the prognosis of kidney cancer according to the gender of the patient with kidney cancer may further include judging that the relapse rate of kidney cancer in the patient with kidney cancer is high when the gender of the patient with kidney cancer is female and the mutation is identified in the gene coding for one selected from the group consisting of ACSS3, ARSF, CFP, FAM47A, ZNF449, and SCRN1.

[0056] As described above, the mutation of at least one gene selected from a gene group consisting of ACSS3, ADAM21, AFF2, ALG13, BAP1, BRWD3, COL4A5, CPEB1, ERBB2, HSP90AA1, IRAK1, KDMSC, KDM6A, LRP12, NCOA6, NHS, RGAG1, SCAF1, SH3TC1, TBC1D8B, TET2, TEX13A, ULK3, WNK3, ARSF, CFP, FAM47A, PHF16, ZNF449, and SCRN1 is used as the mutation of the gene of the present invention to verify that there is a difference in gene mutations according to the gender of a patient who develops cancer, particularly kidney cancer, but this fact is still unknown. Also, the mutation of at least one gene selected from a gene group consisting of ACSS3, ALG13, ARSF, CFP, FAM47A, KDM6A, PHF16, ZNF449, and SCRN1 may be used to diagnose the prognosis of cancer, particularly kidney cancer, in a patient having a certain gender, but this fact is also still unknown. Further, there is no report on the fact that the overall survival rate or disease-free survival rate may be different in each of the genes. The present inventors have first found that the mutation of the genes may be used as a diagnostic marker capable of predicting a difference in therapeutic effect against kidney cancer or diagnosing the prognosis of the patient with kidney cancer according to the gender of the patient with kidney cancer.

[0057] The method for providing information required to predict a difference in therapeutic effect against kidney cancer according to the gender of the patient with kidney cancer according to the present invention may be used to diagnose a gene mutation in kidney cancer based on the gender, increase the survival rate of the patient with kidney cancer, or reduce the relapse rate of kidney cancer. Because the therapeutic effect against kidney cancer may be predicted and the survival rate of the patient with kidney cancer or the relapse rate of kidney cancer may be predicted using the information on the gene mutation which varies depending on the gender of the patient who develops kidney cancer, the method for diagnosing the prognosis of kidney cancer according to the present invention may be used to screen therapeutic agents suitable for each patient and select therapeutic methods so as to provide information, thereby effectively designing a therapeutic strategy for kidney cancer.

MODE FOR INVENTION

[0058] Hereinafter, the present invention will be described in further detail with reference to examples and experimental examples thereof.

[0059] However, it should be understood that the following examples are just preferred examples for the purpose of illustration only and is not intended to limit or define the scope of the invention.

Example 1

Acquisition of Genetic Information and Clinical Information

[0060] To check whether the genes of (ACSS3, ADAM21, AFF2, ALG13, BAP1, BRWD3, COL4A5, CPEB1, ERBB2, HSP90AA1, IRAK1, KDMSC, KDM6A, LRP12, NCOA6, NHS, RGAG1, SCAF1, SH3TC1, TBC1D8B, TET2, TEX13A, ULK3, WNK3, ARSF, CFP, FAM47A, PHF16, ZNF449, and SCRN1) may be used as a kidney cancer marker according to the gender of a patient with kidney cancer, the data on the relapse, metastasis, death, and observation time of 417 patients with clear cell renal cell carcinoma whose genetic information and clinical information were all secured were obtained from The Cancer Genome Atlas (TCGA), and used for analyses. The following Table 1 lists the data on the relapse, metastasis, and death of the patients with clear cell renal cell carcinoma.

TABLE-US-00001 TABLE 1 Total Gender Number of Ratio Male Female patients (%) Relapse 0 148 (54.6%) 81 (55.5%) 229 55.2% 1 77 (28.4%) 32 (21.9%) 109 26.1% Not 46 (17.0%) 33 (22.6%) 79 18.7% detected Metas- 0 224 (82.7%) 127 (87.0%) 351 84.2% tasis 1 47 (17.3%) 19 (13.0%) 66 15.8% Death 0 181 (66.8%) 89 (61.0%) 270 65.0% 1 90 (33.2%) 57 (39.0%) 147 35.0% Total number 271 146 417 of patients

Example 2

Confirmation of Usability as Gender-Specific Marker

[0061] 417 patients were divided into two groups based on the gender thereof to check a correlation between of the gender and the mutations of the candidate genes in Example 1 using three feature selection methods (Information Gain, Chi-Square, and MR). Mutation positions of the genes are listed in the following Tables 2 to 6.

TABLE-US-00002 TABLE 2 Accession AA Copy Mutation Start End Gene No. change Type # COSMIC Assessor Chr Pos Pos Ref Var ACSS3 NM_024560.3 R634* Nonsense Diploid 4 chr12 81647354 81647354 C T X152_splice Splice Gain chr12 81503485 81503485 T C G268D Missense Gain 1 Low chr12 81536908 81536908 G A ADAM21 NM_003813.3 N265Y Missense ShallowDel 2 Medium chr14 70925009 70925009 A T R408C Missense Diploid 3 Medium chr14 70925438 70925438 C T T589S Missense Diploid 1 Low chr14 70925981 70925981 A T I161V Missense Diploid 3 Low chr14 70924697 70924697 A G AFF2 NM_002025.3 S770F Missense DeepDel 1 Low chr23 148037884 148037884 C T P513H Missense Diploid 1 Medium chr23 148035250 148035250 C A T640N Missense Gain 1 Low chr23 148037494 148037494 C A I149K Missense Diploid 1 Neutral chr23 147743694 147743694 T A I149K Missense Diploid 1 Neutral chr23 147743694 147743694 T A I149K Missense Diploid 1 Neutral chr23 147743694 147743694 T A ALG13 NM_001099922.2 P925T Missense Diploid Low chr23 110987973 110987973 C A L195Pfs*23 FS del Diploid chr23 110951455 110951455 T -- V456E Missense Diploid Medium chr23 110964871 110964871 T A BAP1 NM_004656.3 M1? Nonstart ShallowDel 6 chr3 52443894 52443894 T C G128* Nonsense ShallowDel 2 chr3 52441470 52441470 C A E402* Nonsense ShallowDel chr3 52438515 52438515 C A E283Gfs*52 FS del ShallowDel 1 chr3 52439864 52439864 T -- V335Efs*56 FS del ShallowDel 1 chr3 52439219 52439238 GCTG -- CCTG GAGG CTTC ACCA Q253* Nonsense ShallowDel 2 chr3 52440295 52440295 G A Q267* Nonsense ShallowDel 1 chr3 52439913 52439913 G A

TABLE-US-00003 TABLE 3 Accession AA Copy Mutation Start End Gene No. change Type # COSMIC Assessor Chr Pos Pos Ref Var BAP1 NM_004656.3 S460* Nonsense ShallowDel 3 chr3 52437782 52437782 G C F170V Missense ShallowDel 4 High chr3 52441262 52441262 A C K711Sfs*25 FS del ShallowDel 1 chr3 52436362 52436362 T -- Y627* Nonsense ShallowDel 1 chr3 52437163 52437163 G C R717Gfs*19 FS del ShallowDel 1 chr3 52436345 52436345 G -- X23_splice Splice ShallowDel chr3 52443729 52443729 C T S279* Nonsense ShallowDel 1 chr3 52439876 52439876 G T BAP1 NM_004656.3 R60* Nonsense DeepDel 4 chr3 52442567 52442567 G A M1? Nonstart ShallowDel 6 chr3 52443892 52443892 C T M1? Nonstart ShallowDel 6 chr3 52443892 52443892 C T R700Gfs*36 FS del ShallowDel 1 chr3 52436397 52436397 C -- X41_splice Splice ShallowDel chr3 52443568 52443568 A G Q40* Nonsense ShallowDel 2 chr3 52443574 52443574 G A Q156* Nonsense ShallowDel 1 chr3 52441304 52441304 G A K626* Nonsense ShallowDel 1 chr3 52437168 52437168 T A D74Efs*4 FS del ShallowDel 1 chr3 52442523 52442523 A -- X41_splice Splice ShallowDel chr3 52443568 52443568 A T D407Vfs*23 FS del ShallowDel 2 chr3 52438499 52438499 T -- F170C Missense ShallowDel 4 High chr3 52441261 52441261 A C X23_splice Splice ShallowDel chr3 52443623 52443647 ACCT -- GCGA TGAG GAAA GGAA AGCA G X311_splice Splice ShallowDel chr3 52439311 52439311 C A E31A Missense ShallowDel 5 High chr3 52443600 52443600 T G N78S Missense ShallowDel 2 Neutral chr3 52442512 52442512 T C N78S Missense ShallowDel 2 Neutral chr3 52442512 52442512 T C L49V Missense ShallowDel 2 High chr3 52442600 52442600 G C D75G Missense ShallowDel 1 Neutral chr3 52442521 52442521 T C S10T Missense ShallowDel 4 High chr3 52443866 52443866 C G N229H Missense ShallowDel 1 Medium chr3 52440367 52440367 T G G109V Missense ShallowDel 1 High chr3 52442023 52442023 C A L17P Missense ShallowDel 1 Medium chr3 52443747 52443747 A G A145G Missense ShallowDel 1 Medium chr3 52441418 52441418 G C K659Del IF del DeepDel chr3 52436801 52436803 CTT -- A1061T Missense Diploid 2 Medium chr23 79948521 79948521 C T

TABLE-US-00004 TABLE 4 Accession AA Copy Gene No. change Type # COSMIC BRWD3 NM_153252.4 G287A Missense Diploid 1 I1747N Missense Diploid 1 COL4A5 NM_000495.4 P1184L Missense Diploid 1 P756S Missense Diploid 1 P1365S Missense Diploid G1427V Missense Diploid X1510_splice Splice Diploid A1656T Missense Diploid CPEB1 NM_030594.4 S393R Missense Diploid G136V Missense Diploid X499_splice Splice Diploid ERBB2 NM_004448.3 E1114G Missense Diploid 1 S649T Missense Diploid 1 V219I Missense Diploid 1 N388Qfs*14 FS ins Diploid HSP90AA1 NM_001017963.2 D512N Missense ShallowDel 2 H806R Missense Diploid 1 I325T Missense ShallowDel 1 L167V Missense ShallowDel 1 Mutation Start End Gene Assessor Chr Pos Pos Ref Var BRWD3 Neutral chr23 79991541 79991541 C G Neutral chr23 79932277 79932277 A T COL4A5 Medium chr23 107909822 107909822 C T Medium chr23 107849993 107849993 C T Medium chr23 107924995 107924995 C T High chr23 107929324 107929324 G T chr23 107935977 107935977 G T Neutral chr23 107938641 107938641 G A CPEB1 Medium chr15 83221251 83221251 G C Neutral chr15 83226709 83226709 C A chr15 83215272 83215272 C A ERBB2 Low chr17 37883729 37883729 A G Low chr17 37876087 37876087 G C Neutral chr17 37866350 37866350 G A chr17 37871549 37871550 -- C HSP90AA1 High chr14 102550300 102550300 C T High chr14 102548486 102548486 T C High chr14 102551690 102551690 A G Medium chr14 102552583 102552583 G C

TABLE-US-00005 TABLE 5 Accession AA Copy Gene No. change Type # COSMIC IRAK1 NM_001569.3 Q280* Nonsense Diploid 1 V548M Missense Diploid 1 Q584K Missense Diploid 1 KDM5C NM_004187.3 R681* Nonsense Diploid 3 Q813* Nonsense Diploid 2 E1152K Missense Diploid 1 X321_splice Splice Diploid T471Vfs*5 FS del Diploid R1458W Missense Diploid 1 G536W Missense Diploid 1 E284* Nonsense Diploid 1 Q1427Pfs*50 FS del Diploid 1 C730R Missense Diploid 2 E592V Missense Diploid 1 E798* Nonsense Diploid 1 C512W Missense Diploid 1 Y639* Nonsense Diploid 1 S1110* Nonsense Diploid 1 E122Vfs*14 FS del Diploid 1 K459* Nonsense Diploid 1 E1131Sfs*16 FS del Diploid 1 C730F Missense Diploid 2 H988Tfs*18 FS del Diploid 1 H733P Missense Diploid 1 P27Lfs*46 FS del Diploid 1 F56Cfs*18 FS del Diploid 1 D1414Efs*54 FS del Diploid 1 R215* Nonsense Diploid 1 G845Rfs*2 FS del ShallowDel Mutation Start End Gene Assessor Chr Pos Pos Ref Var IRAK1 chr23 153283528 153283528 G A Neutral chr23 153278782 153278782 C T Low chr23 153278674 153278674 G T KDM5C chr23 53230752 53230752 G A chr23 53227751 53227751 G A Medium chr23 53223905 53223905 C T chr23 53244975 53244975 A G chr23 53240028 53240031 GGTA -- Low chr23 53222460 53222460 G A High chr23 53239736 53239736 C A chr23 53245090 53245090 C A chr23 53222653 53222656 GGCT -- Medium chr23 53228214 53228214 A G High chr23 53231127 53231127 T A chr23 53227796 53227796 C A High chr23 53239905 53239905 G C chr23 53230876 53230877 -- T chr23 53224222 53224222 G C chr23 53247129 53247135 CCAC -- CTT chr23 53240705 53240705 T A chr23 53224160 53224160 C -- Medium chr23 53228213 53228213 C A chr23 53225887 53225887 G -- Medium chr23 53228204 53228204 T G chr23 53253992 53253992 G -- chr23 53250081 53250082 AA -- chr23 53222684 53222694 TGTG -- GTTC TCA chr23 53246339 53246339 T A chr23 53227036 53227042 GTAGACC --

TABLE-US-00006 TABLE 6 Accession AA Copy Gene No. change Type # COSMIC KDM6A NM_021140.3 A30V Missense Diploid 1 A1246Pfs*19 FS del Diploid V156Del IF del ShallowDel LRP12 NM_013437.4 S622L Missense Diploid 1 E639K Missense Diploid 2 V671I Missense Gain 1 NCOA6 NM_001242539.2 G164E Missense Diploid 1 N877I Missense Gain 1 N864Y Missense Gain 1 V1444A Missense Diploid 1 H832Sfs*47 FS ins Gain NHS NM_198270.3 C360R Missense Diploid P1107A Missense Diploid 1 D1069H Missense Diploid 2 RGAG1 NM_020769.2 A1015G Missense Diploid 1 M858V Missense Diploid 1 G1053R Missense Diploid 1 SCAF1 NM_021228.2 A219Sfs*11 FS ins ShallowDel P211Tfs*19 FS ins Diploid P211Tfs*19 FS ins Diploid A216Pfs*94 FS del Diploid Mutation Start End Gene Assessor Chr Pos Pos Ref Var KDM6A Medium chr23 44732886 44732886 C T chr23 44949174 44949174 A -- chr23 44879876 44879878 GGT -- LRP12 Low chr8 105503616 105503616 G A Neutral chr8 105503566 105503566 C T Neutral chr8 105503470 105503470 C T NCOA6 Low chr20 33356290 33356290 C T Low chr20 33337368 33337368 T A Neutral chr20 33337408 33337408 T A Neutral chr20 33329729 33329729 A G chr20 33337505 33337506 -- G NHS Low chr23 17742451 17742451 T C Low chr23 17745608 17745608 C G Medium chr23 17745494 17745494 G C RGAG1 Low chr23 109696889 109696889 C G Neutral chr23 109696417 109696417 A G Low chr23 109697002 109697002 G C SCAF1 chr19 50154294 50154295 -- C chr19 50154270 50154271 -- C chr19 50154270 50154271 -- C chr19 50154291 50154294 TGCA --

TABLE-US-00007 TABLE 7 Accession AA Copy Mutation Start End Gene No. change Type # COSMIC Assessor Chr Pos Pos Ref Var SH3TC1 NM_018986.4 A375V Missense Diploid 1 Neutral chr4 8224578 8224578 C T R238Sfs*38 FS del Diploid chr4 8218768 8218768 G -- L180F Missense Diploid 1 Neutral chr4 8217896 8217896 G T TBC1D8B NM_017752.2 G1059V Missense Diploid 2 Neutral chr23 106117008 106117008 G T A614T Missense ShallowDel 1 Medium chr23 106093257 106093257 G A S861* Nonsense Gain 1 chr23 106109183 106109183 C G Y815F Missense Diploid J Medium chr23 106109045 106109045 A T Y815F Missense Diploid 3 Medium chr23 106109045 106109045 A T Y815F Missense ShallowDel 3 Medium chr23 106109045 106109045 A T TET2 NM_001127208.2 Q317K Missense ShallowDel 1 Low chr4 106156048 106156048 C A K326* Nonsense Diploid 1 chr4 106156075 106156075 A T L757V Missense Diploid Neutral chr4 106157368 106157368 C G V449E Missense Diploid Low chr4 106156445 106156445 T A N1714K Missense Diploid 1 Medium chr4 106196809 106196809 T G D194E Missense Diploid 1 Low chr4 106155681 106155681 C A N1390H Missense Diploid 1 Medium chr4 106190890 106190890 A C R1451Q Missense Diploid 2 Medium chr4 106193890 106193890 G A M600I Missense ShallowDel 1 Neutral chr4 106156899 106156899 G A P554S Missense ShallowDel 1 Neutral chr4 106156759 106156759 C T TEX13A NM_001291277.1 R393S Missense Diploid Medium chr23 104463697 104463697 C A X199_splice Splice Diploid 2 chr23 104464282 104464282 C -- X199_splice Splice Diploid 2 chr23 104464282 104464282 C -- Y257D Missense Diploid Low chr23 104464107 104464107 A C ULK3 NM_001099436.3 Q81Sfs*41 FS del Diploid chr15 75134624 75134624 A -- D79H Missense Diploid Medium chr15 75134629 75134629 C G L77V Missense Diploid Low chr15 75134635 75134635 G C WNK3 NM_001002838.3 S865* Nonsense Diploid 1 chr23 54276546 54276546 G T E537G Missense Diploid 1 Low chr23 54321069 54321069 T C Y589* Nonsense Diploid 1 chr23 54319687 54319687 A T

[0062] The correlation between the mutagenesis of the candidate genes and the gender of the patients with kidney cancer was confirmed with respect to each the gender groups. A P-value of less than 0.05 was considered to be statistically significant. The following Tables 8 and 11 list information on the related candidate genes (M0: No distant metastasis, and M1: Distant metastasis).

TABLE-US-00008 TABLE 8 Total No. of patients with identified Fisher's Mutation type Gender gene Exact Missense Missense In- Metastasis Metastasis M F mutations (P-value) Mutation(%) Truncating (P) (D) frame Cytoband M0 M1 (%) ACSS3 0 3 3 0.042 0.72% 2 1 0 0 12q21.31 1 2 66.70% ADAM21 0 4 4 0.015 0.96% 0 4 0 0 14q24.1 4 0 0.00% AFF2 1 5 6 0.022 1.44% 0 6 0 0 Xq28 5 1 16.70% ALG13 0 3 3 0.042 0.72% 1 2 0 0 Xq23 3 0 0.00% AOC2 2 2 4 0.614 0.96% 3 1 0 0 17q21 4 0 0.00% AR 0 1 1 0.35 0.24% 0 1 0 0 Xq12 1 0 0.00% ARSF 0 1 1 0.35 0.24% 0 1 0 0 Xp22.3 1 0 0.00% ASUN 1 2 3 0.281 0.72% 1 2 0 0 12p11.23 2 1 33.30% ASXL2 2 4 6 0.19 1.44% 4 1 0 1 2p24.1 4 2 33.30% ASXL3 7 0 7 0.102 1.68% 0 7 0 0 18q12.1 4 3 42.90% AVPR2 0 2 2 0.122 0.48% 0 2 0 0 Xq28 2 0 0.00% BAP1 12 25 37 <0.001 8.87% 25 8 3 1 3p21.1 26 11 29.70% BCOR 2 0 2 0.544 0.48% 1 1 0 0 Xq25-q26.1 1 1 50.00% BHLHB9 3 0 3 0.555 0.72% 0 3 0 0 Xq23 3 0 0.00% BRWD3 0 3 3 0.042 0.72% 0 3 0 0 Xq21.1 3 0 0.00% CDCA7 0 2 2 0.122 0.48% 0 2 0 0 2q31.1 2 0 0.00% CELSR1 7 0 7 0.102 1.68% 3 4 0 0 22q13.31 5 2 28.60% CFP 1 3 4 0.126 0.96% 1 3 0 0 Xp11.4 3 1 25.00% CLN8 0 2 2 0.122 0.48% 0 2 0 0 8p23 2 0 0.00%

TABLE-US-00009 TABLE 9 Total No. of patients with identified Fisher's Mutation type Gender gene Exact Mutation Missense Missense In- Metastasis Metastasis M F mutations (P-value) (%) Truncating (P) (D) frame Cytoband M0 M1 (%) COL4A5 1 5 6 0.022 1.44% 1 5 0 0 Xq22 5 1 16.70% CPEB1 0 3 3 0.042 0.72% 1 2 0 0 15q25.2 2 1 33.30% CYLC1 0 2 2 0.122 0.48% 0 2 0 0 Xq21.1 2 0 0.00% DYSF 2 4 6 0.19 1.44% 2 3 0 1 2p13.2 4 2 33.30% ERBB2 0 4 4 0.015 0.96% 1 3 0 0 17q12 4 0 0.00% FAM47A 1 3 4 0.126 0.96% 0 2 0 2 Xp21.1 3 1 25.00% FRMD7 4 0 4 0.302 0.96% 2 2 0 0 Xp22.2 3 1 25.00% FRMPD4 4 0 4 0.302 0.96% 3 1 0 0 Xp22.2 4 0 0.00% GABRQ 2 4 6 0.19 1.44% 2 4 0 0 Xq28 5 1 16.70% GPR45 0 3 3 0.042 0.72% 1 2 0 0 2q12.1 2 1 33.30% HAUS7 2 0 2 0.544 0.48% 0 2 0 0 Xq28 1 1 50.00% HSP90AA1 0 4 4 0.015 0.96% 0 4 0 0 14q32.31 4 0 0.00% IRAK1 0 3 3 0.042 0.72% 1 2 0 0 Xq28 3 0 0.00% ITIH6 0 1 1 0.35 0.24% 0 1 0 0 Xp11.22- 1 0 0.00% p11.21 KDM5C 3 23 26 <0.001 6.24% 18 8 0 0 Xp11.22- 22 4 15.40% p11.21 KDM6A 0 3 3 0.042 0.72% 1 1 0 1 Xp11.2 3 0 0.00% LPAR4 0 2 2 0.122 0.48% 1 1 0 0 Xq21.1 2 0 0.00% LRP12 0 3 3 0.042 0.72% 0 3 0 0 8q22.2 3 0 0.00% MAGEB10 0 2 2 0.122 0.48% 0 2 0 0 Xp21.1 2 0 0.00%

TABLE-US-00010 TABLE 10 Total No. of patients with identified Fisher's Gender gene Exact Mutation type M F mutations (P-value) Mutation(%) Truncating MAGEB16 0 2 2 0.122 0.48% 0 MAGED1 2 0 2 0.544 0.48% 0 MAP3K15 1 3 4 0.126 0.96% 2 MED14 4 1 5 0.661 1.20% 1 NBPF10 4 4 8 0.459 1.92% 2 NCOA6 0 4 4 0.015 0.96% 1 NCOR1P1 Null 20p11.1 Null NHS 0 3 3 0.042 0.72% 0 NOX1 2 2 4 0.614 0.96% 2 PABPC3 9 1 10 0.176 2.40% 1 PHF16(JADE3) 0 2 2 0.122 0.48% 0 POTEH-AS1 Null 22q11.1 Null PRRG3 0 2 2 0.122 0.48% 0 RGAG1 0 3 3 0.042 0.72% 0 SCAF1 0 4 4 0.015 0.96% 4 SCRN1 0 2 2 0.122 0.48% 1 SH3TC1 0 3 3 0.042 0.72% 1 SMC1A 0 2 2 0.122 0.48% 1 SYTL4 0 1 1 0.35 0.24% 0 Mutation type Missense Missense In- Metastasis Metastasis (P) (D) frame Cytoband M0 M1 (%) MAGEB16 2 0 0 Xp21.1 2 0 0.00% MAGED1 2 0 0 Xp11.23 2 0 0.00% MAP3K15 2 0 0 Xp22.12 3 1 25.00% MED14 4 0 0 Xp11.4 5 0 0.00% NBPF10 6 0 0 1q21.1 6 2 25.00% NCOA6 3 0 0 20q11.22 4 0 0.00% NCOR1P1 NHS 3 0 0 Xp22.13 3 0 0.00% NOX1 2 0 0 Xq22 4 0 0.00% PABPC3 9 0 0 13q12-ql3 10 0 0.00% PHF16(JADE3) 2 0 0 Xp11.23 2 0 0.00% POTEH-AS1 PRRG3 2 0 0 Xq28 2 0 0.00% RGAG1 3 0 0 Xq23 3 0 0.00% SCAF1 0 0 0 19q13.33 3 1 25.00% SCRN1 1 0 0 7p14.3 1 1 50.00% SH3TC1 2 0 0 4p16.1 3 0 0.00% SMC1A 1 0 0 Xp11.22- 2 0 0.00% p11.21 SYTL4 1 0 0 Xq21.33 1 0 0.00%

TABLE-US-00011 TABLE 11 Total No. of patients with identified Fisher's Mutation type Gender gene Exact Mutation Missense Missense In- Metastasis Metastasis M F mutations (P-value) (%) Truncating (P) (D) frame Cytoband M0 M1 (%) TBC1D8B 1 5 6 0.022 1.44% 1 5 0 0 Xq22.3 6 0 0.00% TET2 9 0 9 0.03 2.16% 1 8 0 0 4q24 3 6 66.70% TEX13A 0 4 4 0.015 0.96% 2 2 0 0 Xq22.3 4 0 0.00% TFDP3 1 2 3 0.281 0.72% 0 3 0 0 Xq26.2 3 0 0.00% TRO 0 2 2 0.122 0.48% 1 1 0 0 Xp11.22- 2 0 0.00% p11.21 ULK3 0 3 3 0.042 0.72% 1 2 0 0 15q24.1 3 0 0.00% USP51 1 4 5 0.53 1.20% 1 4 0 0 Xp11.21 3 2 40.00% WNK3 0 3 3 0.042 0.72% 2 1 0 0 Xp11.22 2 1 33.30% ZMYM3 1 1 2 1 0.48% 0 2 0 0 Xq13.1 2 0 0.00% ZNF318 2 5 7 0.054 1.68% 2 5 0 0 6p21.1 6 1 14.30% ZNF449 0 1 1 0.35 0.24% 0 1 0 0 Xq26.3 1 0 0.00%

[0063] From the analysis results, it was confirmed that there were the genes whose P-values were shown to be greater than or equal to 0.05 compared to the other groups even when the genes had mutations in each of the gender groups, and also confirmed that there were the genes whose P-values were shown to be less than 0.05 while the genes had the mutations. Because the mutant genes whose P-values were less than 0.05 compared to the other groups correlated with the certain gender group compared to the other groups, the mutant genes were defined as gender-specific genes. For example, it can be seen that there were a large total number of patients in which AOC2, AR, and ARSF were mutated, but the AOC2, AR, and ARSF mutants had a high P-value of 0.05 or more, there was no correlation between the gender of the patients and the mutations of these genes. On the other hand, it was confirmed that, because the ACSS3, ADAM21, AFF2, ALG13, BAP1, BRWD3, COL4A5, CPEB1, ERBB2, HSP90AA1, IRAK1, KDMSC, KDM6A, LRP12, NCOA6, NHS, RGAG1, SCAF1, SH3TC1, TBC1D8B, TET2, TEX13A, ULK3, and WNK3 genes has a P-value of less than 0.05 in comparison between the groups, there was a correlation between the gender of the patients and the mutagenesis of these genes.

[0064] FIG. 1 shows the results of analyzing the correlation between the gender of patients and the mutations of genes. As shown in FIG. 1, it was confirmed that there were a larger number of patients having the mutant genes in the female groups than in the male groups in the case of the ACSS3, ADAM21, AFF2, ALG13, BAP1, BRWD3, COL4A5, CPEB1, ERBB2, HSP90AA1, IRAK1, KDMSC, KDM6A, LRP12, NCOA6, NHS, RGAG1, SCAF1, SH3TC1, TBC1D8B, TEX13A, ULK3, and WNK3 genes, and there were a larger number of patients having the mutant gene in the male groups than in the female groups in the case of the TET2 gene.

[0065] From the results, it can be seen that the mutations of ACSS3, ADAM21, AFF2, ALG13, BAP1, BRWD3, COL4A5, CPEB1, ERBB2, HSP90AA1, IRAK1, KDMSC, KDM6A, LRP12, NCOA6, NHS, RGAG1, SCAF1, SH3TC1, TBC1D8B, TEX13A, ULK3, and WNK3 were able to be used as the markers specific to the female groups, and that the mutation of TET2 was able to be used as the marker specific to the male groups.

Example 3

Confirmation of Applicability as Survival-Specific Markers According to Gender

[0066] It was confirmed whether there were survival-specific mutant genes among the candidate genes according to the gender. The analyses were performed in the same manner as in Example 2. Mutation positions of the respective genes are listed in Table 12.

TABLE-US-00012 TABLE 12 Accession AA Copy Gene No. change Type # COSMIC ACSS3 NM_024560.3 R634* Nonsense Diploid 4 X152_splice Splice Gain G268D Missense Gain 1 ALG13 NM_001099922.2 P925T Missense Diploid L195Pfs*23 FS del Diploid V456E Missense Diploid ARSF NM_001201538.1 I42F Missense Diploid 1 CFP NM_001145252.1 S27L Missense Diploid 2 R359Q Missense Diploid 1 E135K Missense Diploid 1 E323Gfs*34 FS ins Gain 1 FAM47A NM_203408.3 R505H Missense ShallowDel 3 E507Q Missense ShallowDel 6 L235_H246Del IF del Diploid L235_H246Del IF del Diploid KDM6A NM_021140.3 A30V Missense Diploid 1 A1246Pfs*19 FS del Diploid V156Del IF del ShallowDel PHF16(JADE3) NM_001077445.2 K656Q Missense Diploid R207W Missense ShallowDel ZNF449 NM_152695.5 F183I Missense Diploid 1 SCRN1 NM_001145514.1 D427Y Missense Gain A257Cfs*34 FS ins Diploid Mutation Start End Gene Assessor Chr Pos Pos Ref Var ACSS3 chr12 81647354 81647354 C T chr12 81503485 81503485 T C Low chr12 81536908 81536908 G A ALG13 Low chr23 110987973 110987973 C A chr23 110951455 110951455 T -- Medium chr23 110964871 110964871 T A ARSF Medium chr23 2990179 2990179 A T CFP Medium chr23 47489070 47489070 G A Low chr23 47485783 47485783 C T Low chr23 47487501 47487501 C T chr23 47485891 47485892 -- C FAM47A Neutral chr23 34148882 34148882 C T Low chr23 34148877 34148877 C G chr23 34149658 34149693 ATGG -- GACA CTCC AGTC TCTG GAGG CTCC GGGC GGAG chr23 34149658 34149693 ATGG -- GACA CTCC AGTC TCTG GAGG CTCC GGGC GGAG KDM6A Medium chr23 44732886 44732886 C T chr23 44949174 44949174 A -- chr23 44879876 44879878 GGT -- PHF16(JADE3) Low chr23 46917973 46917973 A C Medium chr23 46887437 46887437 C T ZNF449 Low chr23 134483227 134483227 T A SCRN1 Medium chr7 29963599 29963599 C A chr7 29980329 29980330 -- C

[0067] An overall survival Kaplan-Meier estimate and a disease-free survival Kaplan-Meier estimate were calculated using a Kaplan-Meier survival analysis method (Spss 21). The 417 target patients volunteered in Example 1 were divided into surviving patients (270) and dead patients (147), and comparative analyses thereof were performed. The overall survival Kaplan-Meier estimate or the disease-free survival Kaplan-Meier estimate was calculated based on the clinical information (occurrence of events (death or relapse), and observation time) on the patients volunteered in Example 1 using the Kaplan-Meier survival analysis method. The event was defined as `death` for the overall survival Kaplan-Meier estimate, and the event was defined as `relapse` for the disease-free survival Kaplan-Meier estimate. To verify whether the mutagenesis in each of the genes correlated with the death of the patients from kidney cancer or the relapse of kidney cancer, the correlation between the mutagenesis and the overall survival Kaplan-Meier estimate, and the correlation between the mutagenesis and the disease-free survival Kaplan-Meier estimate were confirmed, based on the event times of the respective groups obtained in the Kaplan-Meier survival analysis method, using a log rank test. A P-value of less than 0.05 was considered to be statistically significant. Cases with alterations in the query genes of the present invention were used as the experimental groups, and a case without alterations in the query genes of the present invention was used as the control. A median months survival refers to a median value when the survival estimates of the patients from the corresponding groups were listed. A gradient of the survival curve obtained by the Kaplan-Meier survival analysis method was determined by the survival estimates.

[0068] To check whether the mutagenesis in each of the candidate genes correlated with the survival rate of the patients with kidney cancer, who had a certain gender, the genetic information on the 417 patient with kidney cancer obtained in Example 1 was analyzed. The gender of the patients in which the mutations of the ACSS3, ALG13, ARSF, CFP, FAM47A, KDM6A, PHF16, ZNF449, and SCRN1 genes were identified was listed in Table 13.

TABLE-US-00013 TABLE 13 Gender group Total number of patients with M F identified gene mutations ACSS3 0 3 3 ALG13 0 3 3 ARSF 0 1 1 CFP 1 3 4 FAM47A 1 3 4 KDM6A 0 3 3 PHF16 0 2 2 ZNF449 0 1 1 SCRN1 0 2 2

[0069] As shown in FIGS. 2 to 10, it can be seen that, because the probability of the null hypothesis being true was shown to be greater than or equal to 99.5% when it is assumed that the mutagenesis of the ACSS3, ALG13, ARSF, CFP, FAM47A, KDM6A, PHF16, ZNF449, and SCRN1 genes correlated with the survival rates of the females of the patients with kidney cancer in comparison between the groups, that is, the probability of the null hypothesis being false was shown to be less than 0.5%, there was the correlation between the mutagenesis of the ACSS3, ALG13, ARSF, CFP, FAM47A, KDM6A, PHF16, ZNF449, and SCRN1 genes and the survival rate of the female patients of the patients with kidney cancer (see information on `Gender group` and information on `Total number of patients with identified gene mutations` listed in Table 13).

[0070] Some mutant genes whose P-values were shown to be greater than or equal to 0.05, the value of which was considered to be insignificant, when only the correlation between the mutagenesis and the gender was verified in Example 1 had a P-value of less than 0.05, the value of which was considered to be significant, when the correlation between the mutagenesis and the survival rates of the patients with kidney cancer who had a certain gender. For example, the P-value of ARSF was considered to be insignificant only when the correlation between the mutagenesis and the gender was verified in Example 1, but considered to be significant when the correlation between the mutation of ARSF and the survival rates of the patients was compared between the gender groups in this example (see information on `Gender group` of Table 13 and the P-values shown in FIGS. 2 to 15).

[0071] The analysis results of survival of the patients with kidney cancer who had the mutant genes are shown in FIGS. 2 to 15.

[0072] From the analysis results, as shown in FIG. 2(A), it was confirmed that at least 50% of the patients with kidney cancer in which the ACSS3 gene was not mutated survived for 80 months or more (blue). On the other hand, it was confirmed that, because at least 50% of the patients with kidney cancer in which the ACSS3 gene was mutated died within 20 months, the patients with kidney cancer in which the ACSS3 gene was mutated had a survival rate lower than the patients with kidney cancer in which the ACSS3 gene was not mutated (red). Referring to FIG. 2(B), it was revealed that at least 50% of the patients with kidney cancer in which the ACSS3 gene was not mutated did not relapse into kidney cancer for 100 months or more (blue), but at least 50% of the patients with kidney cancer relapsed into kidney cancer within 40 months when the ACSS3 gene was mutated (red). Therefore, it can be seen that the mutation of the ACSS3 gene was useful as the marker for predicting the survival rate of the patients with kidney cancer and the relapse of kidney cancer because the patients had a high probability of dying from kidney cancer or relapsing into kidney cancer when the ACSS3 gene was mutated and the gender of the patients with kidney cancer was female.

[0073] As shown in FIG. 3, it was confirmed that at least 50% of the patients with kidney cancer in which the ALG13 gene was not mutated survived for 80 months or more (blue). On the other hand, it was confirmed that, because at least 50% of the patients with kidney cancer in which the ALG13 gene was mutated died within 20 months, the patients with kidney cancer in which the ALG13 gene was mutated had a survival rate lower than the patients with kidney cancer in which the ALG13 gene was not mutated (red). Therefore, it can be seen that the mutation of the ALG13 gene was useful as the marker for predicting the survival rate of the patients with kidney cancer because the patients had a high probability of dying from kidney cancer when the ALG13 gene was mutated and the gender of the patients with kidney cancer was female.

[0074] As shown in FIG. 4(A), it was confirmed that at least 50% of the patients with kidney cancer in which the ARSF gene was not mutated survived for 80 months or more (blue). On the other hand, it was confirmed that, because at least 50% of the patients with kidney cancer in which the ARSF gene was mutated died within 20 months, the patients with kidney cancer in which the ARSF gene was mutated had a survival rate lower than the patients with kidney cancer in which the ARSF gene was not mutated (red). Referring to FIG. 4(B), it was revealed that at least 50% of the patients with kidney cancer in which the ARSF gene was not mutated did not relapse into kidney cancer for 100 months or more (blue), but at least 50% of the patients with kidney cancer relapsed into kidney cancer within 20 months when the ARSF gene was mutated (red). Therefore, it can be seen that the mutation of the ARSF gene was useful as the marker for predicting the survival rate of the patients with kidney cancer and the relapse of kidney cancer because the patients had a high probability of dying from kidney cancer or relapsing into kidney cancer when the ARSF gene was mutated and the gender of the patients with kidney cancer was female.

[0075] As shown in FIG. 5(A), it was confirmed that at least 50% of the patients with kidney cancer in which the CFP gene was not mutated survived for 80 months or more (blue). On the other hand, it was confirmed that, because at least 50% of the patients with kidney cancer in which the CFP gene was mutated died within 20 months, the patients with kidney cancer in which the CFP gene was mutated had a survival rate lower than the patients with kidney cancer in which the CFP gene was not mutated (red). Referring to FIG. 5(B), it was revealed that at least 50% of the patients with kidney cancer in which the CFP gene was not mutated did not relapse into kidney cancer for 100 months or more (blue), but at least 50% of the patients with kidney cancer relapsed into kidney cancer within 40 months when the CFP gene was mutated (red). Therefore, it can be seen that the mutation of the CFP gene was useful as the marker for predicting the survival rate of the patients with kidney cancer and the relapse of kidney cancer because the patients had a high probability of dying from kidney cancer or relapsing into kidney cancer when the CFP gene was mutated and the gender of the patients with kidney cancer was female.

[0076] As shown in FIG. 6(A), it was confirmed that at least 50% of the patients with kidney cancer in which the FAM47A gene was not mutated survived for 80 months or more (blue). On the other hand, it was confirmed that, because at least 50% of the patients with kidney cancer in which the FAM47A gene was mutated died within 20 months, the patients with kidney cancer in which the FAM47A gene was mutated had a survival rate lower than the patients with kidney cancer in which the FAM47A gene was not mutated (red). Referring to FIG. 6(B), it was revealed that at least 50% of the patients with kidney cancer in which the FAM47A gene was not mutated did not relapse into kidney cancer for 100 months or more (blue), but at least 50% of the patients with kidney cancer relapsed into kidney cancer within 40 months when the FAM47A gene was mutated (red). Therefore, it can be seen that the mutation of the FAM47A gene was useful as the marker for predicting the survival rate of the patients with kidney cancer and the relapse of kidney cancer because the patients had a high probability of dying from kidney cancer or relapsing into kidney cancer when the FAM47A gene was mutated and the gender of the patients with kidney cancer was female.

[0077] As shown in FIG. 7, it was confirmed that at least 50% of the patients with kidney cancer in which the KDM6A gene was not mutated survived for 80 months or more (blue). On the other hand, it was confirmed that, because at least 50% of the patients with kidney cancer in which the KDM6A gene was mutated died within 20 months, the patients with kidney cancer in which the KDM6A gene was mutated had a survival rate lower than the patients with kidney cancer in which the KDM6A gene was not mutated (red). Therefore, it can be seen that the mutation of the KDM6A gene was useful as the marker for predicting the survival rate of the patients with kidney cancer because the patients had a high probability of dying from kidney cancer when the KDM6A gene was mutated and the gender of the patients with kidney cancer was female.

[0078] As shown in FIG. 8, it was confirmed that at least 50% of the patients with kidney cancer in which the PHF16 gene was not mutated survived for 80 months or more (blue). On the other hand, it was confirmed that, because at least 50% of the patients with kidney cancer in which the PHF16 gene was mutated died within 40 months, the patients with kidney cancer in which the PHF16 gene was mutated had a survival rate lower than the patients with kidney cancer in which the PHF16 gene was not mutated (red). Therefore, it can be seen that the mutation of the PHF16 gene was useful as the marker for predicting the survival rate of the patients with kidney cancer because the patients had a high probability of dying from kidney cancer when the PHF16 gene was mutated and the gender of the patients with kidney cancer was female.

[0079] Referring to FIG. 9, it was revealed that at least 50% of the patients with kidney cancer in which the SCRN1 gene did not relapsed into kidney cancer for 100 months or more (blue), but at least 50% of the patients with kidney cancer relapsed into kidney cancer within 20 months when the SCRN1 gene was mutated (red). Therefore, it can be seen that the mutation of the SCRN1 gene was useful as the marker for predicting the relapse of kidney cancer because the patients had a high probability of relapsing into kidney cancer when the SCRN1 gene was mutated and the gender of the patients with kidney cancer was female.

[0080] As shown in FIG. 10(A), it was confirmed that at least 50% of the patients with kidney cancer in which the ZNF449 gene was not mutated survived for 80 months or more (blue). On the other hand, it was confirmed that, because at least 50% of the patients with kidney cancer in which the ZNF449 gene was mutated died within 10 months, the patients with kidney cancer in which the ZNF449 gene was mutated had a survival rate lower than the patients with kidney cancer in which the ZNF449 gene was not mutated (red). Referring to FIG. 10(B), it was revealed that at least 50% of the patients with kidney cancer in which the ZNF449 gene did not relapsed into kidney cancer for 100 months or more (blue), but at least 50% of the patients with kidney cancer relapsed into kidney cancer within 20 months when the ZNF449 gene was mutated (red). Therefore, it can be seen that the mutation of the ZNF449 gene was useful as the marker for predicting the survival rate of the patients with kidney cancer or the relapse of kidney cancer because the patients had a high probability of dying from kidney cancer or relapsing into kidney cancer when the ZNF449 gene was mutated and the gender of the patients with kidney cancer was female.

[0081] From the above results, it can be seen that the survival rate of the patients with kidney cancer who had a certain gender was significantly reduced, or the relapse rate of kidney cancer in the patients with kidney cancer was increased when any one gene selected from the group consisting of ACSS3, ALG13, ARSF, CFP, FAM47A, KDM6A, PHF16, ZNF449, and SCRN1 was mutated. Therefore, it can be seen that the prognoses of kidney cancer, particularly the survival of the patients with kidney cancer or the relapse of kidney cancer, were able to be predicted by comparing the gender of the patients to check whether the genes of the present invention were mutated.

Example 4

Manufacture of Chips Capable of Detecting Genes of Examples 2 and 3

[0082] Primer sets for detecting mutations of the genes of Examples 2 and 3 were constructed using Ion AmpliSeq Custom and Community Panels (commercially available from Thermo fisher) with reference to https://tools.thermofishercom/content/sfs/manuals/MAN0006735_AmpliSeq_DNA- _R NA_LibPrep_UG.pdf. To easily detect the mutations, types of chips were selected and the depth of the chips was enhanced. Specifically, information on a panel to be manufactured was input into Ampliseq.com, and the input information was fed back. Thereafter, the related items were discussed to manufacture a panel equipped with a primer set capable of detecting the mutation. Tables 14 to 21 list the primer sets capable of detecting the mutations of the genes of the present invention.

TABLE-US-00014 TABLE 14 SEQ SEQ Lineitem_ ID Ion_AmpliSeq_ ID Ion_AmpliSeq_ Amplicon_ Insert_ Insert_ Amplicon_ Name Chr NO Fwd_Primer* NO Rev_Primer* Start Start Stop Stop ACSS3 chr12 31 GGGATAAGATTG 32 GAAGGCTCTAC 8150 8150 8150 8150 CTATCATCTATG AATGAGAATGTA 3404 3433 3537 3566 ACAGT TGCTAT ACSS3 chr12 33 TTCAGTCAGATG 34 ACAGTCATGTG 8153 8153 8153 8153 CTCAGACTTAAA ACTGGGCTTTT 6787 6817 6938 6960 TAGATT ACSS3 chr12 35 CTCTAGATATAA 36 CCATTGACAATG 8164 8164 8164 8164 ATGCAACAGAG GCAGATAAAGC 7268 7297 7411 7436 GAGCAA TG ADAM21 chr14 37 GGGCTTTCGAG 38 TGCTACTTCCTT 7092 7092 7092 7092 GAGTATTAAAAA CTCTGTTAAGCC 4606 4634 4735 4759 TAAGT ADAM21 chr14 39 GTATTTCTTGTT 40 ATGCTGTAGCTG 7092 7092 7092 7092 GTCAACATAGTG GGAAAGACTG 4919 4949 5070 5092 GATTCC ADAM21 chr14 41 CTTAAACCAGG 42 GTCTTGTTCACA 7092 7092 7092 7092 GATCATGTCTGC CTGCTGTACG 5377 5402 5487 5509 AT ADAM21 chr14 43 GATGTCTTTTGT 44 GGCCACACACA 7092 7092 7092 7092 GGGAGAGTTCA GTACCATCTTT 5885 5911 6037 6059 ATG AFF2 chrX 45 TCACCAGGATAA 46 AGTCTGCATCTT 1477 1477 1477 1477 TACCCATCCTTC GTTTGGCTGA 4362 4364 4377 4379 A 3 8 5 7 AFF2 chrX 47 TCGGAGAGCAG 48 CTGTGGGACAG 1480 1480 1480 1480 CTCTGAGT GCAGATCAT 3518 3519 3529 3531 0 9 6 6 AFF2 chrX 49 GGCTTTGAAGC 50 GGGTCATGAAG 1480 1480 1480 1480 ATAAGTTGTCAA CTCCACACTTT 3739 3742 3755 3757 CA 9 4 0 2 AFF2 chrX 51 GCCAAATCCAA 52 AGAGGTTTTTC 1480 1480 1480 1480 GGAAATCTGTG AGGTTCTCATGA 3780 3782 3795 3797 GT TCTC 5 9 2 9 ALG13 chrX 53 TCCGGATACCTG 54 CATCCATTGATG 1109 1109 1109 1109 CATAAGCAAG CCTCATTCAAA 5136 5138 5151 5154 GAC 7 9 5 1 ALG13 chrX 55 GAAGACTAAGG 56 TCCTGTTGATAT 1109 1109 1109 1109 ATTGTGAGTTTG TTCTTTACCTTT 6478 6481 6492 6495 TAGCA TCTGCT 5 3 9 9 ALG13 chrX 57 TCTTTGTTAGTG 58 AGTCTCTCCCA 1109 1109 1109 1109 ATTGCCTCACCA CATCAAGAGCA 8788 8791 8803 8805 T 6 1 4 6

TABLE-US-00015 TABLE 15 SEQ SEQ Lineitem_ ID Ion_AmpliSeq_ ID Ion_AmpliSeq_ Amplicon_ Insert_ Insert_ Amplicon_ Name Chr NO Fwd_Primer* NO Rev_Primer* Start Start Stop Stop BAP1 chr3 59 GTAGGAGAGAA 60 GTGGAGGCTGA 5243 5243 5243 5243 GAAGACTGAGA GATTGCAAACT 6693 6720 6840 6863 GCACT A BAP1 chr3 61 TTCCAATCAAG 62 GTCGTGGAAGC 5243 5243 5243 5243 AACTTGGCACC CACGGACA 7065 7088 7218 7237 T BAP1 chr3 63 GCCGTGTCTGTA 64 CCATCAACGTC 5243 5243 5243 5243 CTCTCATTGC TTGGCTGAGAA 7674 7696 7808 7830 BAP1 chr3 65 AACCTGGTAGC 66 TTGTCCCAGGA 5243 5243 5243 5243 CTTAGAAAGCT GGAAGAAGACC 8439 8462 8588 8611 G T BAP1 chr3 67 GGGACTTGGCA 68 ATCCCACAGCC 5243 5243 5243 5243 TAATTGTGATTG CTCCCAACAAA 9134 9158 9248 9270 T BAP1 chr3 69 GCTTCACCACTA 70 GGGAGACTGTG 5243 5243 5243 5243 GCTTGGGTTT AGCTTTTCTTGG 9230 9252 9353 9376 BAP1 chr3 71 GGACTTGTTGCT 72 GGGTCTACCCT 5243 5243 5243 5243 GGCTGACTT TTCTCCTCTGA 9836 9857 9948 9970 BAP1 chr3 73 GTATGTTCACGA 74 CGACCGCAGGA 5244 5244 5244 5244 ATCAGAGACAA TCAAGTATGAG 0173 0200 0325 0347 ATGC BAP1 chr3 75 CAGCCTGGCCT 76 CAGGATATCTGC 5244 5244 5244 5244 CATACTTGATC CTCAACCTGAT 0317 0339 0440 0464 G BAP1 chr3 77 CATGGTGCCTAC 78 CCTGAGAAGCA 5244 5244 5244 5244 CATGGTCAAT GAATGGCCTTA 1178 1200 1291 1313 BAP1 chr3 79 CGCACTGCACT 80 GCCAAGGCCCA 5244 5244 5244 5244 AAGGCCATT TAATAGCCATG 1282 1302 1418 1440 BAP1 chr3 81 CACACACCTGG 82 CCCATAGTCCTA 5244 5244 5244 5244 CATGGCTATTA CCTGAGGAGAA 1408 1430 1510 1534 A BAP1 chr3 83 CTGAAACCCTT 84 TTGGTTTCACA 5244 5244 5244 5244 GGTGAAGTCCT GCTGATACCCA 1981 2003 2082 2105 A BAP1 chr3 85 ATCCCACCCTCC 86 CCCAGCCCTGT 5244 5244 5244 5244 AAACAAAGCA ATATGGATTTAT 2453 2475 2601 2627 CTT BAP1 chr3 87 GCTGCTGCTTTC 88 GGGTGCAAGTG 5244 5244 5244 5244 TGTGAGATTTT GAGGAGATCTA 3443 3466 3593 3615 BAP1 chr3 89 CCCTGACATTTG 90 TCGGTAAGAGC 5244 5244 5244 5244 CTCTGAAGGT CTTTTCTCCCT 3570 3592 3710 3732 BAP1 chr3 91 TCTTACCGAAAT 92 AAGATGAATAA 5244 5244 5244 5244 CTTCCACGAGC GGGCTGGCTGG 3724 3747 3875 3897 BAP1 chrX 93 CTTACTGAACA 94 GTGGGAACAGA 7994 7994 7994 7994 CTGTAACACTG GCTAATATTCTC 8434 8462 8580 8608 GAAAGA AAGAG

TABLE-US-00016 TABLE 16 SEQ SEQ Lineitem_ ID Ion_AmpliSeq_ ID Ion_AmpliSeq_ Amplicon_ Insert_ Insert_ Amplicon_ Name Chr NO Fwd_Primer* NO Rev_Primer* Start Start Stop Stop BRWD3 chrX 95 AGAGGATCCTC 96 CTAGAGGAGCT 7993 7993 7993 7993 AGTGGACACAA ACCAGAGCCAA 2193 2215 2343 2367 AC BRWD3 chrX 97 ATTGTTTTTACA 98 TTGATGTTAGGC 7999 7999 7999 7999 TGCCATTGCCAG TGAACATGAAA 1496 1522 1615 1645 AA ACTTTTT COL4A5 chrX 99 ATTAAATTCTCT 100 TGGGAAACCAC 1078 1078 1078 1078 GTGGCAAACAA GATCACCTTTT 4989 4992 5004 5006 TAAGGAC 3 3 5 7 COL4A5 chrX 101 CAGCTGGACAG 102 GTGTGTGGTAG 1079 1079 1079 1079 AAGGGTGAA CTTAGTAAGAA 0980 0982 0991 0993 AGAAGAT 1 1 0 9 COL4A5 chrX 103 CAAAAACTGGT 104 TGGAGGACCAG 1079 1079 1079 1079 TTCTCTCACACC CATCTCCTTTA 2488 2490 2503 2505 AAT 0 6 2 4 COL4A5 chrX 105 CCTCATTCTTTT 106 TCTCTCAGACTC 1079 1079 1079 1079 CCTGTAGGTCCA AAAGACTTTCC 2924 2926 2938 2941 A CT 2 7 8 3 COL4A5 chrX 107 CCTTGAAAGGC 108 TCTTGAAGCAA 1079 1079 1079 1079 TGTTTGCTATTG AGTTGCAAACA 3588 3591 3603 3606 T TTATTGA 9 3 4 3 COL4A5 chrX 109 CTGCTTGGAAG 110 CCCTAGCATCTC 1079 1079 1079 1079 AGTTTCGTTCAG TGAAGGAAGCT 3855 3857 3870 3872 0 3 1 4 CPEB1 chr15 111 CCCACCTGATCT 112 TGGCCAATAATG 8321 8321 8321 8321 CGACAGAAGA TGCCCTTCTT 5186 5208 5335 5357 CPEB1 chr15 113 CACAAGAAAAT 114 AAGTCTGTCCG 8322 8322 8322 8322 CCAGTGCCTCA ATCCTTGCTTC 1163 1186 1315 1337 A CPEB1 chr15 115 CTAACTGAGGG 116 GCTGTTGGCTG 8322 8322 8322 8322 TGCTGGAAACT CAAAGAAAACT 6619 6641 6770 6793 A ERBB2 chr17 117 GTTTGAGTGAA 118 GATCTCTTCCAG 3787 3787 3787 3787 GGCATTCATGGT AGTCTCAAACA 1434 1457 1582 1608 CTT ERBB2 chr17 119 CAAGAGGGTGG 120 GAGTGAAGGGC 3787 3787 3787 3787 TTCCCAGAATT AATGAAGGGTA 5993 6015 6108 6130 ERBB2 chr17 121 GGCTGGCTCCG 122 CAACGTAGCCA 3788 3788 3788 3788 ATGTATTTGAT TCAGTCTCAGA 3628 3650 3751 3773

TABLE-US-00017 TABLE 17 SEQ SEQ Lineitem_ ID Ion_AmpliSeq_ ID Ion_AmpliSeq_ Amplicon_ Insert_ Insert_ Amplicon_ Name Chr NO Fwd_Primer* NO Rev_Primer* Start Start Stop Stop HSP90AA1 chr14 123 ATTACATAGTAT 124 CGACAAGTCTG 1025 1025 1025 1025 AAGGCTTACCC TGAAGGATCTG 4842 4845 4854 4857 AGACCA G 7 6 9 2 HSP90AA1 chr14 125 CCTGATAACTTT 126 GTCCTTGGAATG 1025 1025 1025 1025 CAAAATTTTGCT ACTCAGTGCAT 5022 5026 5034 5036 TTGTTGC 9 0 0 3 HSP90AA1 chr14 127 CAGACAGAAAT 128 CAGGTGAACCT 1025 1025 1025 1025 TCACTCTGCAAT ATGGGTCGT 5159 5162 5175 5177 TACATAAAA 7 9 1 1 HSP90AA1 chr14 129 CCCAAGAAGTT 130 TGAGACGTTCG 1025 1025 1025 1025 CACACTGAAAC CCTTTCAGG 5249 5252 5264 5266 C 9 2 5 5 IRAK1 chrX 131 CGCCTAGGCTCT 132 CCCGCAGGAGA 1532 1532 1532 1532 CGTCACT ACTCCTAC 7864 7866 7878 7880 4 3 2 1 IRAK1 chrX 133 CCAGGTGTCAG 134 ACAGGTTTCGT 1532 1532 1532 1532 GAGTGCTTT CACCCAAACA 8340 8342 8355 8357 1 1 4 5 KDM5C chrX 135 TCCGTACCCTCT 136 TGTCTTTCTGCC 5322 5322 5322 5322 TTGGCTCTAG TGTCTGTAATCA 2382 2404 2516 2541 C KDM5C chrX 137 CCAGAAGTGTG 138 AGTTGACTGGC 5322 5322 5322 5322 CGGATCCTC CCTGTGTTG 2621 2641 2768 2788 KDM5C chrX 139 CCCACACACAC 140 CTGTCCTGGGTA 5322 5322 5322 5322 AGATAGAGGTT TGGCAGATC 3786 3809 3917 3938 G KDM5C chrX 141 CCATCTGTGTCG 142 GTTCTCTGCCCA 5322 5322 5322 5322 AAGCTCCTT TGTGCAGAT 4090 4111 4229 4250 KDM5C chrX 143 CTCTTCTGGGTC 144 CCTAGCCCTGCT 5322 5322 5322 5322 TCCACTCAAC GTGGATAAAG 5798 5820 5943 5965 KDM5C chrX 145 CAGGTTGTTCAT 146 AGTCTTAGCATA 5322 5322 5322 5322 CTGGTCCAGAA GACATGGAGGG 6986 7009 7102 7127 AA KDM5C chrX 147 GCCTCACTCAG 148 CCTCTGCCTCTA 5322 5322 5322 5322 GCAGTTCTTTA TTCAATACTGCC 7723 7745 7847 7873 TA KDM5C chrX 149 CTACTGGAGCA 150 GATGATGAGCG 5322 5322 5322 5322 CTTGCAGAGAT CCAGTGTATCA 8174 8196 8276 8298

TABLE-US-00018 TABLE 18 SEQ SEQ Lineitem_ ID Ion_AmpliSeq_ ID Ion_AmpliSeq_ Amplicon_ Insert_ Insert_ Amplicon_ Name Chr NO Fwd_Primer* NO Rev_Primer* Start Start Stop Stop KDM5C chrX 151 CCCGAACTTCC 152 CCAGAGAAGCT 5323 5323 5323 5323 ACCAGAATAGG AGACCTGAACC 0683 0705 0807 0830 T KDM5C chrX 153 CCATCTTGCAGA 154 GAAGCAGGAGG 5323 5323 5323 5323 TAAGCTCCTCA GTTGTAGAGAA 0839 0862 0981 1004 G KDM5C chrX 155 GCAAAGTTGTA 156 CAGGAAAATCT 5323 5323 5323 5323 GCCTTGGTTGA CTATCTCAACAG 1067 1089 1174 1201 CCAT KDM5C chrX 157 GAGGTCAGGCT 158 CCTGCATGACC 5323 5323 5323 5323 GGCTATCAAAT AAGGTGTGATT 9653 9675 9789 9811 KDM5C chrX 159 GGAGCCCACAC 160 GTACTGTGCCA 5323 5323 5323 5323 TGACTTGATTC CATCAATGCAG 9811 9833 9963 9985 KDM5C chrX 161 ATGCCAGAGATA 162 GTTCCCTAGGCT 5323 5323 5324 5324 TCTGCATTGATG AAAGAAAATGA 9951 9976 0094 0124 T CTTAAGA KDM5C chrX 163 AGATACTAAATG 164 TAGCATTGAGG 5324 5324 5324 5324 ATTTGCCTAAGC AAGATGTGACT 0617 0646 0764 0790 TCACA GTTG KDM5C chrX 165 GGGAATGCTTAT 166 CCTAAGACCTT 5324 5324 5324 5324 TGAAGGGACAA CCTGGAGAGCA 4917 4942 5055 5078 GA A KDM5C chrX 167 GTAGCCTCATGG 168 CCATTTTTCTCT 5324 5324 5324 5324 TCATCTTGGT CTCCCAGATAA 5003 5025 5151 5177 GGA KDM5C chrX 169 TCCCTCCACCTC 170 TAATGAGGAGA 5324 5324 5324 5324 AAAGCTCTAA AGGACAAGGAA 6280 6302 6406 6436 TACAAACC KDM5C chrX 171 GCAAGGAGCCA 172 CTACAGGCCTA 5324 5324 5324 5324 ATATTTTTGCCT CTCCCTCACATA 7043 7066 7194 7217 KDM5C chrX 173 ACCACCAGCTC 174 CTTTTGGTGACT 5324 5325 5325 5325 CTAGTCTTCTC TCCGGTCTTACA 9997 0019 0144 0168 KDM5C chrX 175 CGATGGGCCTGA 176 GCGCCATGAGT 5325 5325 5325 5325 TTTTCGC CCTTAAGG 3960 3979 4115 4134 KDM6A chrX 177 CCAAGCAAGAA 178 AGACTCATAGT 4487 4487 4487 4487 TTCATGCACGT CTGTGTTCACTT 9794 9816 9938 9966 TGAAC KDM6A chrX 179 CACTGTTCATTG 180 AAAAAGGAACA 4494 4494 4494 4494 GGTTCAGGCTA GTCCTATTGGAT 9108 9131 9215 9245 ATAATCC

TABLE-US-00019 TABLE 19 SEQ SEQ Lineitem_ ID Ion_AmpliSeq_ ID Ion_AmpliSeq_ Amplicon_ Insert_ Insert_ Amplicon_ Name Chr NO Fwd_Primer* NO Rev_Primer* Start Start Stop Stop LRP12 chr8 181 ACCTCGGGTACT 182 AAGTTTGTTTTC 1055 1055 1055 1055 CTGAGTTGAG CGTGGAGTCTG 0337 0339 0352 0354 A 5 7 2 6 LRP12 chr8 183 TCCACGGAAAA 184 TTCCTATGGCAG 1055 1055 1055 1055 CAAACTTCTGTG GCAGATCAAG 0352 0355 0368 0370 A 9 3 1 3 NCOA6 chr20 185 CTGGGAAGTTT 186 CAAGGAGAGCT 3332 3332 3332 3332 GTTAGGATCCGA TGAATGTGCCT 9645 9669 9793 9815 A NCOA6 chr20 187 CCCAAAATGGC 188 GGCCATGGGAT 3333 3333 3333 3333 CTGCAGATATG GTCTTTCAATG 7295 7317 7434 7456 NCOA6 chr20 189 CTCCACTGAAA 190 GGTGATCCTGCT 3333 3333 3333 3333 GGTGCATTGAA ACTACAGCAAAT 7420 7443 7568 7594 A AA NCOA6 chr20 191 GCAGGGCTCAA 192 TTGGCTCAGAA 3335 3335 3335 3335 ATGATCAAATAA CCGAAGCCAAG 6193 6218 6343 6366 GC A NHS chrX 193 TCCAAGTAAATG 194 GGGATACCCGA 1774 1774 1774 1774 AAAATTTGTTTG GATGGTTTTCC 2356 2386 2505 2527 CCATTT NHS chrX 195 ACAGCAACCCT 196 TCTCCTACTGTG 1774 1774 1774 1774 CTTTAAAAGATG TTCTGCTTATTAT 5415 5441 5558 5588 GAA GAGTA NHS chrX 197 ACCGTCATCCAC 198 CTTAACTTCTTC 1774 1774 1774 1774 TGCATGTTTT AGACTTGTTGAT 5537 5559 5657 5685 GGAC RGAG1 chrX 199 GAATGATGTCAT 200 AGTGTGCACAT 1096 1096 1096 1096 CCATGCCACAA GTCTCCAGAAG 9633 9635 9648 9650 1 4 3 5 RGAG1 chrX 201 GTCCACATTGCA 202 CATGGGCATCGA 1096 1096 1096 1096 AACCAGTGTT TCCAGAAACT 9680 9683 9694 9697 9 1 9 1 RGAG1 chrX 203 CCACATCATTTA 204 TGTGGTGTGGA 1096 1096 1096 1096 TGAGAGCCTCA CATTGTTCCAG 9692 9695 9708 9710 GTT 8 4 0 2

TABLE-US-00020 TABLE 20 SEQ SEQ Lineitem_ ID Ion_AmpliSeq_ ID Ion_AmpliSeq_ Amplicon_ Insert_ Insert_ Amplicon_ Name Chr NO Fwd_Primer* NO Rev_Primer* Start Start Stop Stop SCAF1 chr19 205 CCATGTGTCCCA 206 GGGTTCGTGAG 5014 5014 5014 5014 TTGGCTTCT CAAAGGAGG 5305 5326 5424 5444 SCAF1 chr19 207 CGCTTTAGCTCC 208 ACTAGCGACCC 5014 5014 5014 5014 GCCTCTC AACTCCGC 5405 5424 5555 5574 SCAF1 chr19 209 GGGACCTCCAC 210 CTCACCAGGAT 5014 5014 5014 5014 TCCAAACTCT AAAGGCAGAAG 8240 8261 8372 8396 GA SCAF1 chr19 211 ATGGTCCGCCA 212 GTGCTTCAAGG 5014 5014 5014 5014 GACAGAGA GAGCCAAGAGT 8342 8361 8484 8506 SCAF1 chr19 213 GCACTTGAGTCT 214 CCGCCATACCTT 5014 5014 5014 5014 AGCTGTCAGT TATCATTGGG 8503 8525 8655 8677 SH3TC1 chr4 215 CCACAGGCTTC 216 CAACGCTCACC 8217 8217 8217 8217 ACTCATCACTG TTCTTGGATGA 832 854 972 994 SH3TC1 chr4 217 CAGTGACCACC 218 GGCGGTGAAGA 8218 8218 8218 8218 TCCATCCTTTT GTCTGTTTCC 658 680 804 825 SH3TC1 chr4 219 TCTGTCTGTCAA 220 CCTGGCATCCTC 8224 8224 8224 8224 ATCAAGGAATG CTCAGAAAAG 473 500 623 645 GAAA TBC1D8 chrX 221 ATGAGATACATC 222 CATATCAGTCAT 1060 1060 1060 1060 AGCATGCTAATA GTGTTCTGTCA 9316 9319 9330 9333 GAAGTG GCT 0 0 8 4 TBC1D8B chrX 223 AGCAGACATGG 224 CAGTCAATCTG 1061 1061 1061 1061 TTTTTAAAATCT ATACTGTTCCAA 0894 0897 0909 0912 TCCAAA ATATGG 6 5 1 0 TBC1D8B chrX 225 CCATATTTGGAA 226 TACCAATTGCA 1061 1061 1061 1061 CAGTATCAGATT GAGGAGAATTC 0909 0912 0923 0926 GACTG TTTGAA 2 1 8 6 TBC1D8B chrX 227 TGGAAGGAAAC 228 CAACAGCGATG 1061 1061 1061 1061 TACATAGCCCTA CAAGAATCTGT 1691 1694 1707 1709 CA T 9 4 0 3 TET2 chr4 229 TAACTGCAGTG 230 AGTTCACCATG 1061 1061 1061 1061 GGCCTGAAAAT TGTGTGTTCCA 5560 5562 5575 5577 6 8 1 3 TET2 chr4 231 CCTGTGATGCTG 232 AATTCTTCACCA 1061 1061 1061 1061 ATGATGCTGATA GACGCTAGCTT 5598 5600 5613 5615 3 7 1 4 TET2 chr4 233 GGAAAAAGCAC 234 GCCTTTCAGAA 1061 1061 1061 1061 TCTGAATGGTG AGCATCGGAGA 5636 5638 5651 5653 GA A 3 7 4 7

TABLE-US-00021 TABLE 21 SEQ SEQ Lineitem_ ID Ion_AmpliSeq_ ID Ion_AmpliSeq_ Amplicon_ Insert_ Insert_ Amplicon_ Name Chr NO Fwd_Primer* NO Rev_Primer* Start Start Stop Stop TET2 chr4 235 AACTGCCAGCA 236 TTACGTTTTAGA 1061 1061 1061 1061 GTTGATGAGAA TGGGATTCCGCT 5668 5670 5681 5684 T 1 3 9 4 TET2 chr4 237 CACCAAGCGGA 238 AGCTGTGTTGTT 1061 1061 1061 1061 ATCCCATCTAA TTCTGGGTGTA 5681 5683 5695 5697 6 8 6 9 TET2 chr4 239 AAACACAACCA 240 CCATGAAAACA 1061 1061 1061 1061 TCCCAGAGTTC TTCTTCCACTTT 5728 5730 5743 5745 A AGTCTG 5 8 0 9 TET2 chr4 241 GGGTCACTGCAT 242 GCAGTGTGAGA 1061 1061 1061 1061 GTTTGGACTT ACAGACTCAAC 9083 9085 9093 9095 AG 1 3 2 6 TET2 chr4 243 AAGTCTCTGAC 244 GAAAGCTTTTC 1061 1061 1061 1061 GTGGATGAGTTT AGCTGCAGCTT 9380 9382 9395 9397 G 3 7 5 7 TET2 chr4 245 AGGTTTGGAAAT 246 ATCTAGAGGTG 1061 1061 1061 1061 AGCCAGAGTTTT GCTCCCATGAA 9671 9673 9686 9688 ACA 1 8 3 5 TEX13A chrX 247 TCGAGATATACA 248 CTCATCAGCAA 1044 1044 1044 1044 TGCTTCGGTTCT AGACCTCCAGT 6360 6363 6375 6377 ATTTTG A 5 5 6 9 TEX13A chrX 249 GGGTTCGTGGTT 250 CCTCCATGGAG 1044 1044 1044 1044 CCAGAGAAAT ACCACAGAGAA 6402 6405 6415 6417 8 0 6 8 TEX13A chrX 251 TCTCTCCAGCTT 252 CTGCTGGAGGA 1044 1044 1044 1044 CTCTGTGGT AAAGGAGCAGA 6414 6416 6429 6431 7 8 6 8 ULK3 chr15 253 GCCTGAAGAGA 254 CCAAGAAAAGT 7513 7513 7513 7513 GTGTCCCTTCT CTGAACAAGGC 4560 4582 4700 4724 AT WNK3 chrX 255 GCTGAAGAGAA 256 CCTGGCTTCTTC 5427 5427 5427 5427 GGAGGAGACTG AGTCAATAAGG 6466 6489 6610 6640 A TAAATAA WNK3 chrX 257 GAAACTTGCTG 258 GGCAGGAGCTG 5431 5431 5431 5431 GTAATGTCCTAC CATCAGTTATA 9571 9598 9722 9744 TAGT WNK3 chrX 259 GTGCTGCTGTG 260 GGGATTCTCAG 5432 5432 5432 5432 GTTTTCTTTGTA TGCAAGTCTATG 1002 1025 1135 1159 G

TABLE-US-00022 TABLE 22 SEQ SEQ Lineitem_ ID Ion_AmpliSeq_ ID Ion_AmpliSeq_ Amplicon_ Insert_ Insert_ Amplicon_ Name Chr NO Fwd_ Primer* NO Rev_Primer* Start Stop Start Stop ARSF chrX 261 GTGCATGACGA 262 ACGACTGACGA 2990 2990 2990 2990 CAAGCCTAATAT ACGTATGACTG 128 153 234 256 TG CFPX chrX 263 GCTGTAGCAGT 264 ACATGAAGTCC 4748 4748 4748 4748 GCCGGATAT ATCAGCTGTCA 5743 5763 5843 5867 AG CFP chrX 265 CCGGGATTTCTT 266 TGATTCCCTGCT 4748 4748 4748 4748 GACAGCTGAT TTGGTCCAATC 5835 5857 5940 5963 CFP chrX 267 CCCACTCTGAG 268 GAATGGGCAGT 4748 4748 4748 4748 GACCTCTGTA GCTCTGGAA 7417 7438 7563 7583 CFP chrX 269 GGCAAAGGCAG 270 GTGTCCAGGCC 4748 4748 4748 4748 TGTTGAGAC CACCACAT 8961 8981 9116 9135 FAM47A chrX 271 ACTGGATCTCCG 272 GAGACTGGAGT 3414 3414 3414 3414 ACGAGTGAT GTCCCATCTAAG 9619 9640 9760 9783 JADE3 chrX 273 ACGCCATTGCCA 274 TCCACTCTCACT 4688 4688 4688 4688 TGAAAATATGAA AACCTGATGCA 7346 7371 7497 7520 C JADE3 chrX 275 CCATTCTAGGAG 276 GCCATTGGATTT 4691 4691 4691 4691 TGAAGCAAAGG GGCAAACTTG 7837 7861 7989 8011 A ZNF449 chrX 277 GGAGCTGAACT 278 CATTGAGTAATT 1344 1344 1344 1344 ATGGTGCTACT GGTGTTTCTAAC 8319 8321 8330 8333 CCAAC 0 2 7 6 SCRN1 chr7 279 TTTTGCTGGTAA 280 CCTGGAAGCCA 2996 2996 2996 2996 TTTAGTAAGGTG TGGAAGAAATC 3511 3539 3658 3681 GGAA C SCRN1 chr7 281 AGGGTATGAGA 282 GAACTCAGGAG 2998 2998 2998 2998 AGGAGAATCGT TTACGCTCAGA 0257 0281 0408 0430 GA

[0083] To verify whether the mutations of the genes were detected using the constructed primer sets, the gene mutations verified in Example 2 and a DNA test samples derived from wild-type kidney cancer cells were amplified. Specifically, each of the gene mutations and the DNA test samples used as the test sample was amplified using a primer set corresponding to each of the test samples, respectively. Thereafter, the amplified chips were scanned using a scanner and application program, and analyzed using quantitative analysis software.

[0084] As a result, it can be seen that the mutations of the genes of Examples 2 and 3 were detected using the primer sets constructed in Example 4. On the other hand, the mutations were not detected in the test samples derived from the kidney cancer cells as the control. As described above, because the mutations of genes selected from a gene group consisting of ACSS3, ADAM21, AFF2, ALG13, BAP1, BRWD3, COL4A5, CPEB1, ERBB2, HSP90AA1, IRAK1, KDMSC, KDM6A, LRP12, NCOA6, NHS, RGAG1, SCAF1, SH3TC1, TBC1D8B, TET2, TEX13A, ULK3, WNK3, ARSF, CFP, FAM47A, PHF16, ZNF449, and SCRN1 were detectable using the primer sets listed in Tables 14 to 22, it was possible to predict the overall survival Kaplan-Meier estimates and disease-free survival Kaplan-Meier estimates of the patients with kidney cancer in which the genes were mutated, thereby effectively designing a therapeutic strategy for kidney cancer.

[0085] Although preferred embodiments of the present invention have been shown and described for the purpose of illustration only, it would be appreciated by those skilled in the art that various modifications and changes may be made in these embodiments without departing from the scope of the present invention.

Sequence CWU 1

1

2821686PRTHomo sapiens 1Met Lys Pro Ser Trp Leu Gln Cys Arg Lys Val Thr Ser Ala Gly Gly1 5 10 15Leu Gly Gly Pro Leu Pro Gly Ser Ser Pro Ala Arg Gly Ala Gly Ala 20 25 30Ala Leu Arg Ala Leu Val Val Pro Gly Pro Arg Gly Gly Leu Gly Gly 35 40 45Arg Gly Cys Arg Ala Leu Ser Ser Gly Ser Gly Ser Glu Tyr Lys Thr 50 55 60His Phe Ala Ala Ser Val Thr Asp Pro Glu Arg Phe Trp Gly Lys Ala65 70 75 80Ala Glu Gln Ile Ser Trp Tyr Lys Pro Trp Thr Lys Thr Leu Glu Asn 85 90 95Lys His Ser Pro Ser Thr Arg Trp Phe Val Glu Gly Met Leu Asn Ile 100 105 110Cys Tyr Asn Ala Val Asp Arg His Ile Glu Asn Gly Lys Gly Asp Lys 115 120 125Ile Ala Ile Ile Tyr Asp Ser Pro Val Thr Asn Thr Lys Ala Thr Phe 130 135 140Thr Tyr Lys Glu Val Leu Glu Gln Val Ser Lys Leu Ala Gly Val Leu145 150 155 160Val Lys His Gly Ile Lys Lys Gly Asp Thr Val Val Ile Tyr Met Pro 165 170 175Met Ile Pro Gln Ala Met Tyr Thr Met Leu Ala Cys Ala Arg Ile Gly 180 185 190Ala Ile His Ser Leu Ile Phe Gly Gly Phe Ala Ser Lys Glu Leu Ser 195 200 205Ser Arg Ile Asp His Val Lys Pro Lys Val Val Val Thr Ala Ser Phe 210 215 220Gly Ile Glu Pro Gly Arg Arg Val Glu Tyr Val Pro Leu Val Glu Glu225 230 235 240Ala Leu Lys Ile Gly Gln His Lys Pro Asp Lys Ile Leu Ile Tyr Asn 245 250 255Arg Pro Asn Met Glu Ala Val Pro Leu Ala Pro Gly Arg Asp Leu Asp 260 265 270Trp Asp Glu Glu Met Ala Lys Ala Gln Ser His Asp Cys Val Pro Val 275 280 285Leu Ser Glu His Pro Leu Tyr Ile Leu Tyr Thr Ser Gly Thr Thr Gly 290 295 300Leu Pro Lys Gly Val Ile Arg Pro Thr Gly Gly Tyr Ala Val Met Leu305 310 315 320His Trp Ser Met Ser Ser Ile Tyr Gly Leu Gln Pro Gly Glu Val Trp 325 330 335Trp Ala Ala Ser Asp Leu Gly Trp Val Val Gly His Ser Tyr Ile Cys 340 345 350Tyr Gly Pro Leu Leu His Gly Asn Thr Thr Val Leu Tyr Glu Gly Lys 355 360 365Pro Val Gly Thr Pro Asp Ala Gly Ala Tyr Phe Arg Val Leu Ala Glu 370 375 380His Gly Val Ala Ala Leu Phe Thr Ala Pro Thr Ala Ile Arg Ala Ile385 390 395 400Arg Gln Gln Asp Pro Gly Ala Ala Leu Gly Lys Gln Tyr Ser Leu Thr 405 410 415Arg Phe Lys Thr Leu Phe Val Ala Gly Glu Arg Cys Asp Val Glu Thr 420 425 430Leu Glu Trp Ser Lys Asn Val Phe Arg Val Pro Val Leu Asp His Trp 435 440 445Trp Gln Thr Glu Thr Gly Ser Pro Ile Thr Ala Ser Cys Val Gly Leu 450 455 460Gly Asn Ser Lys Thr Pro Pro Pro Gly Gln Ala Gly Lys Ser Val Pro465 470 475 480Gly Tyr Asn Val Met Ile Leu Asp Asp Asn Met Gln Lys Leu Lys Ala 485 490 495Arg Cys Leu Gly Asn Ile Val Val Lys Leu Pro Leu Pro Pro Gly Ala 500 505 510Phe Ser Gly Leu Trp Lys Asn Gln Glu Ala Phe Lys His Leu Tyr Phe 515 520 525Glu Lys Phe Pro Gly Tyr Tyr Asp Thr Met Asp Ala Gly Tyr Met Asp 530 535 540Glu Glu Gly Tyr Leu Tyr Val Met Ser Arg Val Asp Asp Val Ile Asn545 550 555 560Val Ala Gly His Arg Ile Ser Ala Gly Ala Ile Glu Glu Ser Ile Leu 565 570 575Ser His Gly Thr Val Ala Asp Cys Ala Val Val Gly Lys Glu Asp Pro 580 585 590Leu Lys Gly His Val Pro Leu Ala Leu Cys Val Leu Arg Lys Asp Ile 595 600 605Asn Ala Thr Glu Glu Gln Val Leu Glu Glu Ile Val Lys His Val Arg 610 615 620Gln Asn Ile Gly Pro Val Ala Ala Phe Arg Asn Ala Val Phe Val Lys625 630 635 640Gln Leu Pro Lys Thr Arg Ser Gly Lys Ile Pro Arg Ser Ala Leu Ser 645 650 655Ala Ile Val Asn Gly Lys Pro Tyr Lys Ile Thr Ser Thr Ile Glu Asp 660 665 670Pro Ser Ile Phe Gly His Val Glu Glu Met Leu Lys Gln Ala 675 680 6852722PRTHomo sapiens 2Met Ala Val Asp Gly Thr Leu Val Tyr Ile Arg Val Thr Leu Leu Leu1 5 10 15Leu Trp Leu Gly Val Phe Leu Ser Ile Ser Gly Tyr Cys Gln Ala Gly 20 25 30Pro Ser Gln His Phe Thr Ser Pro Glu Val Val Ile Pro Leu Lys Val 35 40 45Ile Ser Arg Gly Arg Ser Ala Lys Ala Pro Gly Trp Leu Ser Tyr Ser 50 55 60Leu Arg Phe Gly Gly Gln Lys His Val Val His Met Arg Val Lys Lys65 70 75 80Leu Leu Val Ser Arg His Leu Pro Val Phe Thr Tyr Thr Asp Asp Arg 85 90 95Ala Leu Leu Glu Asp Gln Leu Phe Ile Pro Asp Asp Cys Tyr Tyr His 100 105 110Gly Tyr Val Glu Ala Ala Pro Glu Ser Leu Val Val Phe Ser Ala Cys 115 120 125Phe Gly Gly Phe Arg Gly Val Leu Lys Ile Ser Gly Leu Thr Tyr Glu 130 135 140Ile Glu Pro Ile Arg His Ser Ala Thr Phe Glu His Leu Val Tyr Lys145 150 155 160Ile Asn Ser Asn Glu Thr Gln Phe Pro Ala Met Arg Cys Gly Leu Thr 165 170 175Glu Lys Glu Val Ala Arg Gln Gln Leu Glu Phe Glu Glu Ala Glu Asn 180 185 190Ser Ala Leu Glu Pro Lys Ser Ala Gly Asp Trp Trp Thr His Ala Trp 195 200 205Phe Leu Glu Leu Val Val Val Val Asn His Asp Phe Phe Ile Tyr Ser 210 215 220Gln Ser Asn Ile Ser Lys Val Gln Glu Asp Val Phe Leu Val Val Asn225 230 235 240Ile Val Asp Ser Met Tyr Lys Gln Leu Gly Thr Tyr Ile Ile Leu Ile 245 250 255Gly Ile Glu Ile Trp Asn Gln Gly Asn Val Phe Pro Met Thr Ser Ile 260 265 270Glu Gln Val Leu Asn Asp Phe Ser Gln Trp Lys Gln Ile Ser Leu Ser 275 280 285Gln Leu Gln His Asp Ala Ala His Met Phe Ile Lys Asn Ser Leu Ile 290 295 300Ser Ile Leu Gly Leu Ala Tyr Val Ala Gly Ile Cys Arg Pro Pro Ile305 310 315 320Asp Cys Gly Val Asp Asn Phe Gln Gly Asp Thr Trp Ser Leu Phe Ala 325 330 335Asn Thr Val Ala His Glu Leu Gly His Thr Leu Gly Met Gln His Asp 340 345 350Glu Glu Phe Cys Phe Cys Gly Glu Arg Gly Cys Ile Met Asn Thr Phe 355 360 365Arg Val Pro Ala Glu Lys Phe Thr Asn Cys Ser Tyr Ala Asp Phe Met 370 375 380Lys Thr Thr Leu Asn Gln Gly Ser Cys Leu His Asn Pro Pro Arg Leu385 390 395 400Gly Glu Ile Phe Met Leu Lys Arg Cys Gly Asn Gly Val Val Glu Arg 405 410 415Glu Glu Gln Cys Asp Cys Gly Ser Val Gln Gln Cys Glu Gln Asp Ala 420 425 430Cys Cys Leu Leu Asn Cys Thr Leu Arg Pro Gly Ala Ala Cys Ala Phe 435 440 445Gly Leu Cys Cys Lys Asp Cys Lys Phe Met Pro Ser Gly Glu Leu Cys 450 455 460Arg Gln Glu Val Asn Glu Cys Asp Leu Pro Glu Trp Cys Asn Gly Thr465 470 475 480Ser His Gln Cys Pro Glu Asp Arg Tyr Val Gln Asp Gly Ile Pro Cys 485 490 495Ser Asp Ser Ala Tyr Cys Tyr Gln Lys Arg Cys Asn Asn His Asp Gln 500 505 510His Cys Arg Glu Ile Phe Gly Lys Asp Ala Lys Ser Ala Ser Gln Asn 515 520 525Cys Tyr Lys Glu Ile Asn Ser Gln Gly Asn Arg Phe Gly His Cys Gly 530 535 540Ile Asn Gly Thr Thr Tyr Leu Lys Cys His Ile Ser Asp Val Phe Cys545 550 555 560Gly Arg Val Gln Cys Glu Asn Val Arg Asp Ile Pro Leu Leu Gln Asp 565 570 575His Phe Thr Leu Gln His Thr His Ile Asn Gly Val Thr Cys Trp Gly 580 585 590Ile Asp Tyr His Leu Arg Met Asn Ile Ser Asp Ile Gly Glu Val Lys 595 600 605Asp Gly Thr Val Cys Gly Pro Gly Lys Ile Cys Ile His Lys Lys Cys 610 615 620Val Ser Leu Ser Val Leu Ser His Val Cys Leu Pro Glu Thr Cys Asn625 630 635 640Met Lys Gly Ile Cys Asn Asn Lys His His Cys His Cys Gly Tyr Gly 645 650 655Trp Ser Pro Pro Tyr Cys Gln His Arg Gly Tyr Gly Gly Ser Ile Asp 660 665 670Ser Gly Pro Ala Ser Ala Lys Arg Gly Val Phe Leu Pro Leu Ile Val 675 680 685Ile Pro Ser Leu Ser Val Leu Thr Phe Leu Phe Thr Val Gly Leu Leu 690 695 700Met Tyr Leu Arg Gln Cys Ser Gly Pro Lys Glu Thr Lys Ala His Ser705 710 715 720Ser Gly31311PRTHomo sapiens 3Met Asp Leu Phe Asp Phe Phe Arg Asp Trp Asp Leu Glu Gln Gln Cys1 5 10 15His Tyr Glu Gln Asp Arg Ser Ala Leu Lys Lys Arg Glu Trp Glu Arg 20 25 30Arg Asn Gln Glu Val Gln Gln Glu Asp Asp Leu Phe Ser Ser Gly Phe 35 40 45Asp Leu Phe Gly Glu Pro Tyr Lys Val Ala Glu Tyr Thr Asn Lys Gly 50 55 60Asp Ala Leu Ala Asn Arg Val Gln Asn Thr Leu Gly Asn Tyr Asp Glu65 70 75 80Met Lys Asn Leu Leu Thr Asn His Ser Asn Gln Asn His Leu Val Gly 85 90 95Ile Pro Lys Asn Ser Val Pro Gln Asn Pro Asn Asn Lys Asn Glu Pro 100 105 110Ser Phe Phe Pro Glu Gln Lys Asn Arg Ile Ile Pro Pro His Gln Asp 115 120 125Asn Thr His Pro Ser Ala Pro Met Pro Pro Pro Ser Val Val Ile Leu 130 135 140Asn Ser Thr Leu Ile His Ser Asn Arg Lys Ser Lys Pro Glu Trp Ser145 150 155 160Arg Asp Ser His Asn Pro Ser Thr Val Leu Ala Ser Gln Ala Ser Gly 165 170 175Gln Pro Asn Lys Met Gln Thr Leu Thr Gln Asp Gln Ser Gln Ala Lys 180 185 190Leu Glu Asp Phe Phe Val Tyr Pro Ala Glu Gln Pro Gln Ile Gly Glu 195 200 205Val Glu Glu Ser Asn Pro Ser Ala Lys Glu Asp Ser Asn Pro Asn Ser 210 215 220Ser Gly Glu Asp Ala Phe Lys Glu Ile Phe Gln Ser Asn Ser Pro Glu225 230 235 240Glu Ser Glu Phe Ala Val Gln Ala Pro Gly Ser Pro Leu Val Ala Ser 245 250 255Ser Leu Leu Ala Pro Ser Ser Gly Leu Ser Val Gln Asn Phe Pro Pro 260 265 270Gly Leu Tyr Cys Lys Thr Ser Met Gly Gln Gln Lys Pro Thr Ala Tyr 275 280 285Val Arg Pro Met Asp Gly Gln Asp Gln Ala Pro Asp Ile Ser Pro Thr 290 295 300Leu Lys Pro Ser Ile Glu Phe Glu Asn Ser Phe Gly Asn Leu Ser Phe305 310 315 320Gly Thr Leu Leu Asp Gly Lys Pro Ser Ala Ala Ser Ser Lys Thr Lys 325 330 335Leu Pro Lys Phe Thr Ile Leu Gln Thr Ser Glu Val Ser Leu Pro Ser 340 345 350Asp Pro Ser Cys Val Glu Glu Ile Leu Arg Glu Met Thr His Ser Trp 355 360 365Pro Thr Pro Leu Thr Ser Met His Thr Ala Gly His Ser Glu Gln Ser 370 375 380Thr Phe Ser Ile Pro Gly Gln Glu Ser Gln His Leu Thr Pro Gly Phe385 390 395 400Thr Leu Gln Lys Trp Asn Asp Pro Thr Thr Arg Ala Ser Thr Lys Ser 405 410 415Val Ser Phe Lys Ser Met Leu Glu Asp Asp Leu Lys Leu Ser Ser Asp 420 425 430Glu Asp Asp Leu Glu Pro Val Lys Thr Leu Thr Thr Gln Cys Thr Ala 435 440 445Thr Glu Leu Tyr Gln Ala Val Glu Lys Ala Lys Pro Arg Asn Asn Pro 450 455 460Val Asn Pro Pro Leu Ala Thr Pro Gln Pro Pro Pro Ala Val Gln Ala465 470 475 480Ser Gly Gly Ser Gly Ser Ser Ser Glu Ser Glu Ser Ser Ser Glu Ser 485 490 495Asp Ser Asp Thr Glu Ser Ser Thr Thr Asp Ser Glu Ser Asn Glu Ala 500 505 510Pro Arg Val Ala Thr Pro Glu Pro Glu Pro Pro Ser Thr Asn Lys Trp 515 520 525Gln Leu Asp Lys Trp Leu Asn Lys Val Thr Ser Gln Asn Lys Ser Phe 530 535 540Ile Cys Gly Gln Asn Glu Thr Pro Met Glu Thr Ile Ser Leu Pro Pro545 550 555 560Pro Ile Ile Gln Pro Met Glu Val Gln Met Lys Val Lys Thr Asn Ala 565 570 575Ser Gln Val Pro Ala Glu Pro Lys Glu Arg Pro Leu Leu Ser Leu Ile 580 585 590Arg Glu Lys Ala Arg Pro Arg Pro Thr Gln Lys Ile Pro Glu Thr Lys 595 600 605Ala Leu Lys His Lys Leu Ser Thr Thr Ser Glu Thr Val Ser Gln Arg 610 615 620Thr Ile Gly Lys Lys Gln Pro Lys Lys Val Glu Lys Asn Thr Ser Thr625 630 635 640Asp Glu Phe Thr Trp Pro Lys Pro Asn Ile Thr Ser Ser Thr Pro Lys 645 650 655Glu Lys Glu Ser Val Glu Leu His Asp Pro Pro Arg Gly Arg Asn Lys 660 665 670Ala Thr Ala His Lys Pro Ala Pro Arg Lys Glu Pro Arg Pro Asn Ile 675 680 685Pro Leu Ala Pro Glu Lys Lys Lys Tyr Arg Gly Pro Gly Lys Ile Val 690 695 700Pro Lys Ser Arg Glu Phe Ile Glu Thr Asp Ser Ser Thr Ser Asp Ser705 710 715 720Asn Thr Asp Gln Glu Glu Thr Leu Gln Ile Lys Val Leu Pro Pro Cys 725 730 735Ile Ile Ser Gly Gly Asn Thr Ala Lys Ser Lys Glu Ile Cys Gly Ala 740 745 750Ser Leu Thr Leu Ser Thr Leu Met Ser Ser Ser Gly Ser Asn Asn Asn 755 760 765Leu Ser Ile Ser Asn Glu Glu Pro Thr Phe Ser Pro Ile Pro Val Met 770 775 780Gln Thr Glu Ile Leu Ser Pro Leu Arg Asp His Glu Asn Leu Lys Asn785 790 795 800Leu Trp Val Lys Ile Asp Leu Asp Leu Leu Ser Arg Val Pro Gly His 805 810 815Ser Ser Leu His Ala Ala Pro Ala Lys Pro Asp His Lys Glu Thr Ala 820 825 830Thr Lys Pro Lys Arg Gln Thr Ala Val Thr Ala Val Glu Lys Pro Ala 835 840 845Pro Lys Gly Lys Arg Lys His Lys Pro Ile Glu Val Ala Glu Lys Ile 850 855 860Pro Glu Lys Lys Gln Arg Leu Glu Glu Ala Thr Thr Ile Cys Leu Leu865 870 875 880Pro Pro Cys Ile Ser Pro Ala Pro Pro His Lys Pro Pro Asn Thr Arg 885 890 895Glu Asn Asn Ser Ser Arg Arg Ala Asn Arg Arg Lys Glu Glu Lys Leu 900 905 910Phe Pro Pro Pro Leu Ser Pro Leu Pro Glu Asp Pro Pro Arg Arg Arg 915 920 925Asn Val Ser Gly Asn Asn Gly Pro Phe Gly Gln Asp Lys Asn Ile Ala 930 935 940Met Thr Gly Gln Ile Thr Ser Thr Lys Pro Lys Arg Thr Glu Gly Lys945 950 955 960Phe Cys Ala Thr Phe Lys Gly Ile Ser Val Asn Glu Gly Asp Thr Pro 965 970 975Lys Lys Ala Ser Ser Ala Thr Ile Thr Val Thr Asn Thr Ala Ile Ala 980 985 990Thr Ala Thr Val Thr Ala Thr Ala Ile Val Thr Thr Thr Val Thr Ala 995 1000 1005Thr Ala Thr Ala Thr Ala Thr Thr Thr Thr Thr Thr Thr Thr Ile 1010 1015 1020Ser Thr Ile Thr Ser Thr Ile Thr Thr Gly Leu Met Asp Ser Ser 1025 1030 1035His Leu Glu Met Thr Ser Trp Ala Ala Leu Pro Leu Leu Ser Ser 1040 1045 1050Ser Ser Thr Asn Val

Arg Arg Pro Lys Leu Thr Phe Asp Asp Ser 1055 1060 1065Val His Asn Ala Asp Tyr Tyr Met Gln Glu Ala Lys Lys Leu Lys 1070 1075 1080His Lys Ala Asp Ala Leu Phe Glu Lys Phe Gly Lys Ala Val Asn 1085 1090 1095Tyr Ala Asp Ala Ala Leu Ser Phe Thr Glu Cys Gly Asn Ala Met 1100 1105 1110Glu Arg Asp Pro Leu Glu Ala Lys Ser Pro Tyr Thr Met Tyr Ser 1115 1120 1125Glu Thr Val Glu Leu Leu Arg Tyr Ala Met Arg Leu Lys Asn Phe 1130 1135 1140Ala Ser Pro Leu Ala Ser Asp Gly Asp Lys Lys Leu Ala Val Leu 1145 1150 1155Cys Tyr Arg Cys Leu Ser Leu Leu Tyr Leu Arg Met Phe Lys Leu 1160 1165 1170Lys Lys Asp His Ala Met Lys Tyr Ser Arg Ser Leu Met Glu Tyr 1175 1180 1185Phe Lys Gln Asn Ala Ser Lys Val Ala Gln Ile Pro Ser Pro Trp 1190 1195 1200Val Ser Asn Gly Lys Asn Thr Pro Ser Pro Val Ser Leu Asn Asn 1205 1210 1215Val Ser Pro Ile Asn Ala Met Gly Asn Cys Asn Asn Gly Pro Val 1220 1225 1230Thr Ile Pro Gln Arg Ile His His Met Ala Ala Ser His Val Asn 1235 1240 1245Ile Thr Ser Asn Val Leu Arg Gly Tyr Glu His Trp Asp Met Ala 1250 1255 1260Asp Lys Leu Thr Arg Glu Asn Lys Glu Phe Phe Gly Asp Leu Asp 1265 1270 1275Thr Leu Met Gly Pro Leu Thr Gln His Ser Ser Met Thr Asn Leu 1280 1285 1290Val Arg Tyr Val Arg Gln Gly Leu Cys Trp Leu Arg Ile Asp Ala 1295 1300 1305His Leu Leu 131041137PRTHomo sapiens 4Met Lys Cys Val Phe Val Thr Val Gly Thr Thr Ser Phe Asp Asp Leu1 5 10 15Ile Ala Cys Val Ser Ala Pro Asp Ser Leu Gln Lys Ile Glu Ser Leu 20 25 30Gly Tyr Asn Arg Leu Ile Leu Gln Ile Gly Arg Gly Thr Val Val Pro 35 40 45Glu Pro Phe Ser Thr Glu Ser Phe Thr Leu Asp Val Tyr Arg Tyr Lys 50 55 60Asp Ser Leu Lys Glu Asp Ile Gln Lys Ala Asp Leu Val Ile Ser His65 70 75 80Ala Gly Ala Gly Ser Cys Leu Glu Thr Leu Glu Lys Gly Lys Pro Leu 85 90 95Val Val Val Ile Asn Glu Lys Leu Met Asn Asn His Gln Leu Glu Leu 100 105 110Ala Lys Gln Leu His Lys Glu Gly His Leu Phe Tyr Cys Thr Cys Arg 115 120 125Val Leu Thr Cys Pro Gly Gln Ala Lys Ser Ile Ala Ser Ala Pro Gly 130 135 140Lys Cys Gln Asp Ser Ala Ala Leu Thr Ser Thr Ala Phe Ser Gly Leu145 150 155 160Asp Phe Gly Leu Leu Ser Gly Tyr Leu His Lys Gln Ala Leu Val Thr 165 170 175Ala Thr His Pro Thr Cys Thr Leu Leu Phe Pro Ser Cys His Ala Phe 180 185 190Phe Pro Leu Pro Leu Thr Pro Thr Leu Tyr Lys Met His Lys Gly Trp 195 200 205Lys Asn Tyr Cys Ser Gln Lys Ser Leu Asn Glu Ala Ser Met Asp Glu 210 215 220Tyr Leu Gly Ser Leu Gly Leu Phe Arg Lys Leu Thr Ala Lys Asp Ala225 230 235 240Ser Cys Leu Phe Arg Ala Ile Ser Glu Gln Leu Phe Cys Ser Gln Val 245 250 255His His Leu Glu Ile Arg Lys Ala Cys Val Ser Tyr Met Arg Glu Asn 260 265 270Gln Gln Thr Phe Glu Ser Tyr Val Glu Gly Ser Phe Glu Lys Tyr Leu 275 280 285Glu Arg Leu Gly Asp Pro Lys Glu Ser Ala Gly Gln Leu Glu Ile Arg 290 295 300Ala Leu Ser Leu Ile Tyr Asn Arg Asp Phe Ile Leu Tyr Arg Phe Pro305 310 315 320Gly Lys Pro Pro Thr Tyr Val Thr Asp Asn Gly Tyr Glu Asp Lys Ile 325 330 335Leu Leu Cys Tyr Ser Ser Ser Gly His Tyr Asp Ser Val Tyr Ser Lys 340 345 350Gln Phe Gln Ser Ser Ala Ala Val Cys Gln Ala Val Leu Tyr Glu Ile 355 360 365Leu Tyr Lys Asp Val Phe Val Val Asp Glu Glu Glu Leu Lys Thr Ala 370 375 380Ile Lys Leu Phe Arg Ser Gly Ser Lys Lys Asn Arg Asn Asn Ala Val385 390 395 400Thr Gly Ser Glu Asp Ala His Thr Asp Tyr Lys Ser Ser Asn Gln Asn 405 410 415Arg Met Glu Glu Trp Gly Ala Cys Tyr Asn Ala Glu Asn Ile Pro Glu 420 425 430Gly Tyr Asn Lys Gly Thr Glu Glu Thr Lys Ser Pro Glu Asn Pro Ser 435 440 445Lys Met Pro Phe Pro Tyr Lys Val Leu Lys Ala Leu Asp Pro Glu Ile 450 455 460Tyr Arg Asn Val Glu Phe Asp Val Trp Leu Asp Ser Arg Lys Glu Leu465 470 475 480Gln Lys Ser Asp Tyr Met Glu Tyr Ala Gly Arg Gln Tyr Tyr Leu Gly 485 490 495Asp Lys Cys Gln Val Cys Leu Glu Ser Glu Gly Arg Tyr Tyr Asn Ala 500 505 510His Ile Gln Glu Val Gly Asn Glu Asn Asn Ser Val Thr Val Phe Ile 515 520 525Glu Glu Leu Ala Glu Lys His Val Val Pro Leu Ala Asn Leu Lys Pro 530 535 540Val Thr Gln Val Met Ser Val Pro Ala Trp Asn Ala Met Pro Ser Arg545 550 555 560Lys Gly Arg Gly Tyr Gln Lys Met Pro Gly Gly Tyr Val Pro Glu Ile 565 570 575Val Ile Ser Glu Met Asp Ile Lys Gln Gln Lys Lys Met Phe Lys Lys 580 585 590Ile Arg Gly Lys Glu Val Tyr Met Thr Met Ala Tyr Gly Lys Gly Asp 595 600 605Pro Leu Leu Pro Pro Arg Leu Gln His Ser Met His Tyr Gly His Asp 610 615 620Pro Pro Met His Tyr Ser Gln Thr Ala Gly Asn Val Met Ser Asn Glu625 630 635 640His Phe His Pro Gln His Pro Ser Pro Arg Gln Gly Arg Gly Tyr Gly 645 650 655Met Pro Arg Asn Ser Ser Arg Phe Ile Asn Arg His Asn Met Pro Gly 660 665 670Pro Lys Val Asp Phe Tyr Pro Gly Pro Gly Lys Arg Cys Cys Gln Ser 675 680 685Tyr Asp Asn Phe Ser Tyr Arg Ser Arg Ser Phe Arg Arg Ser His Arg 690 695 700Gln Met Ser Cys Val Asn Lys Glu Ser Gln Tyr Gly Phe Thr Pro Gly705 710 715 720Asn Gly Gln Met Pro Arg Gly Leu Glu Glu Thr Ile Thr Phe Tyr Glu 725 730 735Val Glu Glu Gly Asp Glu Thr Ala Tyr Pro Thr Leu Pro Asn His Gly 740 745 750Gly Pro Ser Thr Met Val Pro Ala Thr Ser Gly Tyr Cys Val Gly Arg 755 760 765Arg Gly His Ser Ser Gly Lys Gln Thr Leu Asn Leu Glu Glu Gly Asn 770 775 780Gly Gln Ser Glu Asn Gly Arg Tyr His Glu Glu Tyr Leu Tyr Arg Ala785 790 795 800Glu Pro Asp Tyr Glu Thr Ser Gly Val Tyr Ser Thr Thr Ala Ser Thr 805 810 815Ala Asn Leu Ser Leu Gln Asp Arg Lys Ser Cys Ser Met Ser Pro Gln 820 825 830Asp Thr Val Thr Ser Tyr Asn Tyr Pro Gln Lys Met Met Gly Asn Ile 835 840 845Ala Ala Val Ala Ala Ser Cys Ala Asn Asn Val Pro Ala Pro Val Leu 850 855 860Ser Asn Gly Ala Ala Ala Asn Gln Ala Ile Ser Thr Thr Ser Val Ser865 870 875 880Ser Gln Asn Ala Ile Gln Pro Leu Phe Val Ser Pro Pro Thr His Gly 885 890 895Arg Pro Val Ile Ala Ser Pro Ser Tyr Pro Cys His Ser Ala Ile Pro 900 905 910His Ala Gly Ala Ser Leu Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro 915 920 925Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro 930 935 940Pro Ala Leu Asp Val Gly Glu Thr Ser Asn Leu Gln Pro Pro Pro Pro945 950 955 960Leu Pro Pro Pro Pro Tyr Ser Cys Asp Pro Ser Gly Ser Asp Leu Pro 965 970 975Gln Asp Thr Lys Val Leu Gln Tyr Tyr Phe Asn Leu Gly Leu Gln Cys 980 985 990Tyr Tyr His Ser Tyr Trp His Ser Met Val Tyr Val Pro Gln Met Gln 995 1000 1005Gln Gln Leu His Val Glu Asn Tyr Pro Val Tyr Thr Glu Pro Pro 1010 1015 1020Leu Val Asp Gln Thr Val Pro Gln Cys Tyr Ser Glu Val Arg Arg 1025 1030 1035Glu Asp Gly Ile Gln Ala Glu Ala Ser Ala Asn Asp Thr Phe Pro 1040 1045 1050Asn Ala Asp Ser Ser Ser Val Pro His Gly Ala Val Tyr Tyr Pro 1055 1060 1065Val Met Ser Asp Pro Tyr Gly Gln Pro Pro Leu Pro Gly Phe Asp 1070 1075 1080Ser Cys Leu Pro Val Val Pro Asp Tyr Ser Cys Val Pro Pro Trp 1085 1090 1095His Pro Val Gly Thr Ala Tyr Gly Gly Ser Ser Gln Ile His Gly 1100 1105 1110Ala Ile Asn Pro Gly Pro Ile Gly Cys Ile Ala Pro Ser Pro Pro 1115 1120 1125Ala Ser His Tyr Val Pro Gln Gly Met 1130 11355729PRTHomo sapiens 5Met Asn Lys Gly Trp Leu Glu Leu Glu Ser Asp Pro Gly Leu Phe Thr1 5 10 15Leu Leu Val Glu Asp Phe Gly Val Lys Gly Val Gln Val Glu Glu Ile 20 25 30Tyr Asp Leu Gln Ser Lys Cys Gln Gly Pro Val Tyr Gly Phe Ile Phe 35 40 45Leu Phe Lys Trp Ile Glu Glu Arg Arg Ser Arg Arg Lys Val Ser Thr 50 55 60Leu Val Asp Asp Thr Ser Val Ile Asp Asp Asp Ile Val Asn Asn Met65 70 75 80Phe Phe Ala His Gln Leu Ile Pro Asn Ser Cys Ala Thr His Ala Leu 85 90 95Leu Ser Val Leu Leu Asn Cys Ser Ser Val Asp Leu Gly Pro Thr Leu 100 105 110Ser Arg Met Lys Asp Phe Thr Lys Gly Phe Ser Pro Glu Ser Lys Gly 115 120 125Tyr Ala Ile Gly Asn Ala Pro Glu Leu Ala Lys Ala His Asn Ser His 130 135 140Ala Arg Pro Glu Pro Arg His Leu Pro Glu Lys Gln Asn Gly Leu Ser145 150 155 160Ala Val Arg Thr Met Glu Ala Phe His Phe Val Ser Tyr Val Pro Ile 165 170 175Thr Gly Arg Leu Phe Glu Leu Asp Gly Leu Lys Val Tyr Pro Ile Asp 180 185 190His Gly Pro Trp Gly Glu Asp Glu Glu Trp Thr Asp Lys Ala Arg Arg 195 200 205Val Ile Met Glu Arg Ile Gly Leu Ala Thr Ala Gly Glu Pro Tyr His 210 215 220Asp Ile Arg Phe Asn Leu Met Ala Val Val Pro Asp Arg Arg Ile Lys225 230 235 240Tyr Glu Ala Arg Leu His Val Leu Lys Val Asn Arg Gln Thr Val Leu 245 250 255Glu Ala Leu Gln Gln Leu Ile Arg Val Thr Gln Pro Glu Leu Ile Gln 260 265 270Thr His Lys Ser Gln Glu Ser Gln Leu Pro Glu Glu Ser Lys Ser Ala 275 280 285Ser Asn Lys Ser Pro Leu Val Leu Glu Ala Asn Arg Ala Pro Ala Ala 290 295 300Ser Glu Gly Asn His Thr Asp Gly Ala Glu Glu Ala Ala Gly Ser Cys305 310 315 320Ala Gln Ala Pro Ser His Ser Pro Pro Asn Lys Pro Lys Leu Val Val 325 330 335Lys Pro Pro Gly Ser Ser Leu Asn Gly Val His Pro Asn Pro Thr Pro 340 345 350Ile Val Gln Arg Leu Pro Ala Phe Leu Asp Asn His Asn Tyr Ala Lys 355 360 365Ser Pro Met Gln Glu Glu Glu Asp Leu Ala Ala Gly Val Gly Arg Ser 370 375 380Arg Val Pro Val Arg Pro Pro Gln Gln Tyr Ser Asp Asp Glu Asp Asp385 390 395 400Tyr Glu Asp Asp Glu Glu Asp Asp Val Gln Asn Thr Asn Ser Ala Leu 405 410 415Arg Tyr Lys Gly Lys Gly Thr Gly Lys Pro Gly Ala Leu Ser Gly Ser 420 425 430Ala Asp Gly Gln Leu Ser Val Leu Gln Pro Asn Thr Ile Asn Val Leu 435 440 445Ala Glu Lys Leu Lys Glu Ser Gln Lys Asp Leu Ser Ile Pro Leu Ser 450 455 460Ile Lys Thr Ser Ser Gly Ala Gly Ser Pro Ala Val Ala Val Pro Thr465 470 475 480His Ser Gln Pro Ser Pro Thr Pro Ser Asn Glu Ser Thr Asp Thr Ala 485 490 495Ser Glu Ile Gly Ser Ala Phe Asn Ser Pro Leu Arg Ser Pro Ile Arg 500 505 510Ser Ala Asn Pro Thr Arg Pro Ser Ser Pro Val Thr Ser His Ile Ser 515 520 525Lys Val Leu Phe Gly Glu Asp Asp Ser Leu Leu Arg Val Asp Cys Ile 530 535 540Arg Tyr Asn Arg Ala Val Arg Asp Leu Gly Pro Val Ile Ser Thr Gly545 550 555 560Leu Leu His Leu Ala Glu Asp Gly Val Leu Ser Pro Leu Ala Leu Thr 565 570 575Glu Gly Gly Lys Gly Ser Ser Pro Ser Ile Arg Pro Ile Gln Gly Ser 580 585 590Gln Gly Ser Ser Ser Pro Val Glu Lys Glu Val Val Glu Ala Thr Asp 595 600 605Ser Arg Glu Lys Thr Gly Met Val Arg Pro Gly Glu Pro Leu Ser Gly 610 615 620Glu Lys Tyr Ser Pro Lys Glu Leu Leu Ala Leu Leu Lys Cys Val Glu625 630 635 640Ala Glu Ile Ala Asn Tyr Glu Ala Cys Leu Lys Glu Glu Val Glu Lys 645 650 655Arg Lys Lys Phe Lys Ile Asp Asp Gln Arg Arg Thr His Asn Tyr Asp 660 665 670Glu Phe Ile Cys Thr Phe Ile Ser Met Leu Ala Gln Glu Gly Met Leu 675 680 685Ala Asn Leu Val Glu Gln Asn Ile Ser Val Arg Arg Arg Gln Gly Val 690 695 700Ser Ile Gly Arg Leu His Lys Gln Arg Lys Pro Asp Arg Arg Lys Arg705 710 715 720Ser Arg Pro Tyr Lys Ala Lys Arg Gln 72561802PRTHomo sapiens 6Met Ala Ala Ala Pro Thr Gln Ile Glu Ala Glu Leu Tyr Tyr Leu Ile1 5 10 15Ala Arg Phe Leu Gln Ser Gly Pro Cys Asn Lys Ser Ala Gln Val Leu 20 25 30Val Gln Glu Leu Glu Glu His Gln Leu Ile Pro Arg Arg Leu Asp Trp 35 40 45Glu Gly Lys Glu His Arg Arg Ser Phe Glu Asp Leu Val Ala Ala Asn 50 55 60Ala His Ile Pro Pro Asp Tyr Leu Leu Lys Ile Cys Glu Arg Ile Gly65 70 75 80Pro Leu Leu Asp Lys Glu Ile Pro Gln Ser Val Pro Gly Val Gln Thr 85 90 95Leu Leu Gly Val Gly Arg Gln Ser Leu Leu Arg Asp Ala Lys Asp Cys 100 105 110Lys Ser Thr Leu Trp Asn Gly Ser Ala Phe Ala Ala Leu His Arg Gly 115 120 125Arg Pro Pro Glu Leu Pro Val Asn Tyr Val Lys Pro Pro Asn Val Val 130 135 140Asn Ile Thr Ser Ala Arg Gln Leu Thr Gly Cys Ser Arg Phe Gly His145 150 155 160Ile Phe Pro Ser Ser Ala Tyr Gln His Ile Lys Met His Lys Arg Ile 165 170 175Leu Gly His Leu Ser Ser Val Tyr Cys Val Ala Phe Asp Arg Ser Gly 180 185 190Arg Arg Ile Phe Thr Gly Ser Asp Asp Cys Leu Val Lys Ile Trp Ala 195 200 205Thr Asp Asp Gly Arg Leu Leu Ala Thr Leu Arg Gly His Ser Ala Glu 210 215 220Ile Ser Asp Met Ala Val Asn Tyr Glu Asn Thr Leu Ile Ala Ala Gly225 230 235 240Ser Cys Asp Lys Val Val Arg Val Trp Cys Leu Arg Thr Cys Ala Pro 245 250 255Val Ala Val Leu Gln Gly His Ser Ala Ser Ile Thr Ser Ile Gln Phe 260 265 270Cys Pro Ser Thr Lys Gly Thr Asn Arg Tyr Leu Thr Ser Thr Gly Ala 275 280 285Asp Gly Thr Ile Cys Phe Trp Gln Trp His Val Lys Thr Met Lys Phe 290 295 300Arg Asp Arg Pro Val Lys Phe Thr Glu Arg Ser Arg Pro Gly Val Gln305 310 315 320Ile Ser Cys Ser Ser Phe Ser Ser Gly Gly Met Phe Ile Thr Thr Gly 325 330 335Ser Thr Asp His Val Ile Arg Ile Tyr Tyr

Leu Gly Ser Glu Val Pro 340 345 350Glu Lys Ile Ala Glu Leu Glu Ser His Thr Asp Lys Val Val Ala Val 355 360 365Gln Phe Cys Asn Asn Gly Asp Ser Leu Arg Phe Val Ser Gly Ser Arg 370 375 380Asp Gly Thr Ala Arg Ile Trp Gln Tyr Gln Gln Gln Glu Trp Lys Ser385 390 395 400Ile Val Leu Asp Met Ala Thr Lys Met Thr Gly Asn Asn Leu Pro Ser 405 410 415Gly Glu Asp Lys Ile Thr Lys Leu Lys Val Thr Met Val Ala Trp Asp 420 425 430Arg Tyr Asp Thr Thr Val Ile Thr Ala Val Asn Asn Phe Leu Leu Lys 435 440 445Val Trp Asn Ser Ile Thr Gly Gln Leu Leu His Thr Leu Ser Gly His 450 455 460Asp Asp Glu Val Phe Val Leu Glu Ala His Pro Phe Asp Gln Arg Ile465 470 475 480Ile Leu Ser Ala Gly His Asp Gly Asn Ile Phe Ile Trp Asp Leu Asp 485 490 495Arg Gly Thr Lys Ile Arg Asn Tyr Phe Asn Met Ile Glu Gly Gln Gly 500 505 510His Gly Ala Val Phe Asp Cys Lys Phe Ser Pro Asp Gly Asn His Phe 515 520 525Ala Cys Thr Asp Ser His Gly His Leu Leu Leu Phe Gly Phe Gly Cys 530 535 540Ser Lys Tyr Tyr Glu Lys Ile Pro Asp Gln Met Phe Phe His Thr Asp545 550 555 560Tyr Arg Pro Leu Ile Arg Asp Ala Asn Asn Tyr Val Leu Asp Glu Gln 565 570 575Thr Gln Gln Ala Pro His Leu Met Pro Pro Pro Phe Leu Val Asp Val 580 585 590Asp Gly Asn Pro His Pro Thr Lys Phe Gln Arg Leu Val Pro Gly Arg 595 600 605Glu Asn Cys Lys Asp Glu Gln Leu Ile Pro Gln Leu Gly Tyr Val Ala 610 615 620Asn Gly Asp Gly Glu Val Val Glu Gln Val Ile Gly Gln Gln Thr Asn625 630 635 640Asp Gln Asp Glu Ser Ile Leu Asp Gly Ile Ile Arg Glu Leu Gln Arg 645 650 655Glu Gln Asp Leu Arg Leu Ile Asn Glu Gly Asp Val Pro His Leu Pro 660 665 670Val Asn Arg Ala Tyr Ser Val Asn Gly Ala Leu Arg Ser Pro Asn Met 675 680 685Asp Ile Ser Ser Ser Pro Asn Ile Arg Leu Arg Arg His Ser Ser Gln 690 695 700Ile Glu Gly Val Arg Gln Met His Asn Asn Ala Pro Arg Ser Gln Met705 710 715 720Ala Thr Glu Arg Asp Leu Met Ala Trp Ser Arg Arg Val Val Val Asn 725 730 735Glu Leu Asn Asn Gly Val Ser Arg Val Gln Glu Glu Cys Arg Thr Ala 740 745 750Lys Gly Asp Ile Glu Ile Ser Leu Tyr Thr Val Glu Lys Lys Lys Lys 755 760 765Pro Ser Tyr Thr Thr Gln Arg Asn Asp Tyr Glu Pro Ser Cys Gly Arg 770 775 780Ser Leu Arg Arg Thr Gln Arg Lys Arg Gln His Thr Tyr Gln Thr Arg785 790 795 800Ser Asn Ile Glu His Asn Ser Gln Ala Ser Cys Gln Asn Ser Gly Val 805 810 815Gln Glu Asp Ser Asp Ser Ser Ser Glu Glu Asp Glu Thr Val Gly Thr 820 825 830Ser Asp Ala Ser Val Glu Asp Pro Val Val Glu Trp Gln Ser Glu Ser 835 840 845Ser Ser Ser Asp Ser Ser Ser Glu Tyr Ser Asp Trp Thr Ala Asp Ala 850 855 860Gly Ile Asn Leu Gln Pro Pro Lys Arg Gln Thr Arg Gln Thr Thr Arg865 870 875 880Lys Ile Cys Ser Ser Ser Asp Glu Glu Asn Leu Lys Ser Leu Glu Glu 885 890 895Arg Gln Lys Lys Pro Lys Gln Thr Arg Lys Lys Lys Gly Gly Leu Val 900 905 910Ser Ile Ala Gly Glu Pro Asn Glu Glu Trp Phe Ala Pro Gln Trp Ile 915 920 925Leu Asp Thr Ile Pro Arg Arg Ser Pro Phe Val Pro Gln Met Gly Asp 930 935 940Glu Leu Ile Tyr Phe Arg Gln Gly His Glu Ala Tyr Val Arg Ala Val945 950 955 960Arg Lys Ser Lys Ile Tyr Ser Val Asn Leu Gln Lys Gln Pro Trp Asn 965 970 975Lys Met Asp Leu Arg Glu Gln Glu Phe Val Lys Ile Val Gly Ile Lys 980 985 990Tyr Glu Val Gly Pro Pro Thr Leu Cys Cys Leu Lys Leu Ala Phe Leu 995 1000 1005Asp Pro Ile Ser Gly Lys Met Thr Gly Glu Ser Phe Ser Ile Lys 1010 1015 1020Tyr His Asp Met Pro Asp Val Ile Asp Phe Leu Val Leu His Gln 1025 1030 1035Phe Tyr Asn Glu Ala Lys Glu Arg Asn Trp Gln Ile Gly Asp Arg 1040 1045 1050Phe Arg Ser Ile Ile Asp Asp Ala Trp Trp Phe Gly Thr Val Glu 1055 1060 1065Ser Gln Gln Pro Phe Gln Pro Glu Tyr Pro Asp Ser Ser Phe Gln 1070 1075 1080Cys Tyr Ser Val His Trp Asp Asn Asn Glu Arg Glu Lys Met Ser 1085 1090 1095Pro Trp Asp Met Glu Pro Ile Pro Glu Gly Thr Ala Phe Pro Asp 1100 1105 1110Glu Val Gly Ala Gly Val Pro Val Ser Gln Glu Glu Leu Thr Ala 1115 1120 1125Leu Leu Tyr Lys Pro Gln Glu Gly Glu Trp Gly Ala His Ser Arg 1130 1135 1140Asp Glu Glu Cys Glu Arg Val Ile Gln Gly Ile Asn His Leu Leu 1145 1150 1155Ser Leu Asp Phe Ala Ser Pro Phe Ala Val Pro Val Asp Leu Ser 1160 1165 1170Ala Tyr Pro Leu Tyr Cys Thr Val Val Ala Tyr Pro Thr Asp Leu 1175 1180 1185Asn Thr Ile Arg Arg Arg Leu Glu Asn Arg Phe Tyr Arg Arg Ile 1190 1195 1200Ser Ala Leu Met Trp Glu Val Arg Tyr Ile Glu His Asn Ala Arg 1205 1210 1215Thr Phe Asn Glu Pro Asp Ser Pro Ile Val Lys Ala Ala Lys Ile 1220 1225 1230Val Thr Asp Val Leu Leu Arg Phe Ile Gly Asp Gln Ser Cys Thr 1235 1240 1245Asp Ile Leu Asp Thr Tyr Asn Lys Ile Lys Ala Glu Glu Arg Asn 1250 1255 1260Ser Thr Asp Ala Glu Glu Asp Thr Glu Ile Val Asp Leu Asp Ser 1265 1270 1275Asp Gly Pro Gly Thr Ser Ser Gly Arg Arg Val Lys Cys Arg Gly 1280 1285 1290Arg Arg Gln Ser Leu Lys Cys Asn Pro Asp Ala Trp Lys Lys Gln 1295 1300 1305Cys Lys Glu Leu Leu Ser Leu Ile Tyr Glu Arg Glu Asp Ser Glu 1310 1315 1320Pro Phe Arg Gln Pro Ala Asp Leu Leu Ser Tyr Pro Gly His Gln 1325 1330 1335Glu Gln Glu Gly Glu Ser Ser Glu Ser Val Val Pro Glu Arg Gln 1340 1345 1350Gln Asp Ser Ser Leu Ser Glu Asp Tyr Gln Asp Val Ile Asp Thr 1355 1360 1365Pro Val Asp Phe Ser Thr Val Lys Glu Thr Leu Glu Ala Gly Asn 1370 1375 1380Tyr Gly Ser Pro Leu Glu Phe Tyr Lys Asp Val Arg Gln Ile Phe 1385 1390 1395Asn Asn Ser Lys Ala Tyr Thr Ser Asn Lys Lys Ser Arg Ile Tyr 1400 1405 1410Ser Met Met Leu Arg Leu Ser Ala Leu Phe Glu Ser His Ile Lys 1415 1420 1425Asn Ile Ile Ser Glu Tyr Lys Ser Ala Ile Gln Ser Gln Lys Arg 1430 1435 1440Arg Arg Pro Arg Tyr Arg Lys Arg Leu Arg Ser Ser Ser Ser Ser 1445 1450 1455Leu Ser Ser Ser Gly Ala Pro Ser Pro Lys Gly Lys Gln Lys Gln 1460 1465 1470Met Lys Leu Gln Pro Lys Asn Asp Gln Asn Thr Ser Val Ser His 1475 1480 1485Ala Arg Thr Ser Ser Pro Phe Ser Ser Pro Val Ser Asp Ala Ala 1490 1495 1500Glu Gly Leu Ser Leu Tyr Leu Leu Asp Asp Glu Pro Asp Gly Pro 1505 1510 1515Phe Ser Ser Ser Ser Phe Gly Gly Tyr Ser Arg Ser Gly Asn Ser 1520 1525 1530His Asp Pro Gly Lys Ala Lys Ser Phe Arg Asn Arg Val Leu Pro 1535 1540 1545Val Lys Gln Asp His Ser Leu Asp Gly Pro Leu Thr Asn Gly Asp 1550 1555 1560Gly Arg Glu Pro Arg Thr Gly Ile Lys Arg Lys Leu Leu Ser Ala 1565 1570 1575Ser Glu Glu Asp Glu Asn Met Gly Gly Glu Asp Lys Glu Lys Lys 1580 1585 1590Glu Thr Lys Glu Lys Ser His Leu Ser Thr Ser Glu Ser Gly Glu 1595 1600 1605Leu Gly Ser Ser Leu Ser Ser Glu Ser Thr Cys Gly Ser Asp Ser 1610 1615 1620Asp Ser Glu Ser Thr Ser Arg Thr Asp Gln Asp Tyr Val Asp Gly 1625 1630 1635Asp His Asp Tyr Ser Lys Phe Ile Gln Thr Arg Pro Lys Arg Lys 1640 1645 1650Leu Arg Lys Gln His Gly Asn Gly Lys Arg Asn Trp Lys Thr Arg 1655 1660 1665Gly Thr Gly Gly Arg Gly Arg Trp Gly Arg Trp Gly Arg Trp Ser 1670 1675 1680Arg Gly Gly Arg Gly Arg Gly Gly Arg Gly Arg Gly Ser Arg Gly 1685 1690 1695Arg Gly Gly Gly Gly Thr Arg Gly Arg Gly Arg Gly Arg Gly Gly 1700 1705 1710Arg Gly Ala Ser Arg Gly Ala Thr Arg Ala Lys Arg Ala Arg Ile 1715 1720 1725Ala Asp Asp Glu Phe Asp Thr Met Phe Ser Gly Arg Phe Ser Arg 1730 1735 1740Leu Pro Arg Ile Lys Thr Arg Asn Gln Gly Arg Arg Thr Val Leu 1745 1750 1755Tyr Asn Asp Asp Ser Asp Asn Asp Asn Phe Val Ser Thr Glu Asp 1760 1765 1770Pro Leu Asn Leu Gly Thr Ser Arg Ser Gly Arg Val Arg Lys Met 1775 1780 1785Thr Glu Lys Ala Arg Val Ser His Leu Met Gly Trp Asn Tyr 1790 1795 180071685PRTHomo sapiens 7Met Lys Leu Arg Gly Val Ser Leu Ala Ala Gly Leu Phe Leu Leu Ala1 5 10 15Leu Ser Leu Trp Gly Gln Pro Ala Glu Ala Ala Ala Cys Tyr Gly Cys 20 25 30Ser Pro Gly Ser Lys Cys Asp Cys Ser Gly Ile Lys Gly Glu Lys Gly 35 40 45Glu Arg Gly Phe Pro Gly Leu Glu Gly His Pro Gly Leu Pro Gly Phe 50 55 60Pro Gly Pro Glu Gly Pro Pro Gly Pro Arg Gly Gln Lys Gly Asp Asp65 70 75 80Gly Ile Pro Gly Pro Pro Gly Pro Lys Gly Ile Arg Gly Pro Pro Gly 85 90 95Leu Pro Gly Phe Pro Gly Thr Pro Gly Leu Pro Gly Met Pro Gly His 100 105 110Asp Gly Ala Pro Gly Pro Gln Gly Ile Pro Gly Cys Asn Gly Thr Lys 115 120 125Gly Glu Arg Gly Phe Pro Gly Ser Pro Gly Phe Pro Gly Leu Gln Gly 130 135 140Pro Pro Gly Pro Pro Gly Ile Pro Gly Met Lys Gly Glu Pro Gly Ser145 150 155 160Ile Ile Met Ser Ser Leu Pro Gly Pro Lys Gly Asn Pro Gly Tyr Pro 165 170 175Gly Pro Pro Gly Ile Gln Gly Leu Pro Gly Pro Thr Gly Ile Pro Gly 180 185 190Pro Ile Gly Pro Pro Gly Pro Pro Gly Leu Met Gly Pro Pro Gly Pro 195 200 205Pro Gly Leu Pro Gly Pro Lys Gly Asn Met Gly Leu Asn Phe Gln Gly 210 215 220Pro Lys Gly Glu Lys Gly Glu Gln Gly Leu Gln Gly Pro Pro Gly Pro225 230 235 240Pro Gly Gln Ile Ser Glu Gln Lys Arg Pro Ile Asp Val Glu Phe Gln 245 250 255Lys Gly Asp Gln Gly Leu Pro Gly Asp Arg Gly Pro Pro Gly Pro Pro 260 265 270Gly Ile Arg Gly Pro Pro Gly Pro Pro Gly Gly Glu Lys Gly Glu Lys 275 280 285Gly Glu Gln Gly Glu Pro Gly Lys Arg Gly Lys Pro Gly Lys Asp Gly 290 295 300Glu Asn Gly Gln Pro Gly Ile Pro Gly Leu Pro Gly Asp Pro Gly Tyr305 310 315 320Pro Gly Glu Pro Gly Arg Asp Gly Glu Lys Gly Gln Lys Gly Asp Thr 325 330 335Gly Pro Pro Gly Pro Pro Gly Leu Val Ile Pro Arg Pro Gly Thr Gly 340 345 350Ile Thr Ile Gly Glu Lys Gly Asn Ile Gly Leu Pro Gly Leu Pro Gly 355 360 365Glu Lys Gly Glu Arg Gly Phe Pro Gly Ile Gln Gly Pro Pro Gly Leu 370 375 380Pro Gly Pro Pro Gly Ala Ala Val Met Gly Pro Pro Gly Pro Pro Gly385 390 395 400Phe Pro Gly Glu Arg Gly Gln Lys Gly Asp Glu Gly Pro Pro Gly Ile 405 410 415Ser Ile Pro Gly Pro Pro Gly Leu Asp Gly Gln Pro Gly Ala Pro Gly 420 425 430Leu Pro Gly Pro Pro Gly Pro Ala Gly Pro His Ile Pro Pro Ser Asp 435 440 445Glu Ile Cys Glu Pro Gly Pro Pro Gly Pro Pro Gly Ser Pro Gly Asp 450 455 460Lys Gly Leu Gln Gly Glu Gln Gly Val Lys Gly Asp Lys Gly Asp Thr465 470 475 480Cys Phe Asn Cys Ile Gly Thr Gly Ile Ser Gly Pro Pro Gly Gln Pro 485 490 495Gly Leu Pro Gly Leu Pro Gly Pro Pro Gly Ser Leu Gly Phe Pro Gly 500 505 510Gln Lys Gly Glu Lys Gly Gln Ala Gly Ala Thr Gly Pro Lys Gly Leu 515 520 525Pro Gly Ile Pro Gly Ala Pro Gly Ala Pro Gly Phe Pro Gly Ser Lys 530 535 540Gly Glu Pro Gly Asp Ile Leu Thr Phe Pro Gly Met Lys Gly Asp Lys545 550 555 560Gly Glu Leu Gly Ser Pro Gly Ala Pro Gly Leu Pro Gly Leu Pro Gly 565 570 575Thr Pro Gly Gln Asp Gly Leu Pro Gly Leu Pro Gly Pro Lys Gly Glu 580 585 590Pro Gly Gly Ile Thr Phe Lys Gly Glu Arg Gly Pro Pro Gly Asn Pro 595 600 605Gly Leu Pro Gly Leu Pro Gly Asn Ile Gly Pro Met Gly Pro Pro Gly 610 615 620Phe Gly Pro Pro Gly Pro Val Gly Glu Lys Gly Ile Gln Gly Val Ala625 630 635 640Gly Asn Pro Gly Gln Pro Gly Ile Pro Gly Pro Lys Gly Asp Pro Gly 645 650 655Gln Thr Ile Thr Gln Pro Gly Lys Pro Gly Leu Pro Gly Asn Pro Gly 660 665 670Arg Asp Gly Asp Val Gly Leu Pro Gly Asp Pro Gly Leu Pro Gly Gln 675 680 685Pro Gly Leu Pro Gly Ile Pro Gly Ser Lys Gly Glu Pro Gly Ile Pro 690 695 700Gly Ile Gly Leu Pro Gly Pro Pro Gly Pro Lys Gly Phe Pro Gly Ile705 710 715 720Pro Gly Pro Pro Gly Ala Pro Gly Thr Pro Gly Arg Ile Gly Leu Glu 725 730 735Gly Pro Pro Gly Pro Pro Gly Phe Pro Gly Pro Lys Gly Glu Pro Gly 740 745 750Phe Ala Leu Pro Gly Pro Pro Gly Pro Pro Gly Leu Pro Gly Phe Lys 755 760 765Gly Ala Leu Gly Pro Lys Gly Asp Arg Gly Phe Pro Gly Pro Pro Gly 770 775 780Pro Pro Gly Arg Thr Gly Leu Asp Gly Leu Pro Gly Pro Lys Gly Asp785 790 795 800Val Gly Pro Asn Gly Gln Pro Gly Pro Met Gly Pro Pro Gly Leu Pro 805 810 815Gly Ile Gly Val Gln Gly Pro Pro Gly Pro Pro Gly Ile Pro Gly Pro 820 825 830Ile Gly Gln Pro Gly Leu His Gly Ile Pro Gly Glu Lys Gly Asp Pro 835 840 845Gly Pro Pro Gly Leu Asp Val Pro Gly Pro Pro Gly Glu Arg Gly Ser 850 855 860Pro Gly Ile Pro Gly Ala Pro Gly Pro Ile Gly Pro Pro Gly Ser Pro865 870 875 880Gly Leu Pro Gly Lys Ala Gly Ala Ser Gly Phe Pro Gly Thr Lys Gly 885 890 895Glu Met Gly Met Met Gly Pro Pro Gly Pro Pro Gly Pro Leu Gly Ile 900 905 910Pro Gly Arg Ser Gly Val Pro Gly Leu Lys Gly Asp Asp Gly Leu Gln 915 920 925Gly Gln Pro Gly Leu Pro Gly Pro Thr Gly Glu Lys Gly Ser Lys Gly 930 935 940Glu Pro Gly Leu Pro Gly Pro Pro Gly Pro Met Asp Pro Asn Leu Leu945 950 955 960Gly Ser Lys Gly Glu Lys Gly Glu Pro Gly Leu Pro Gly Ile Pro Gly 965 970 975Val Ser Gly Pro Lys Gly Tyr Gln Gly Leu Pro Gly Asp Pro Gly Gln 980 985 990Pro Gly Leu Ser Gly Gln Pro Gly Leu Pro Gly

Pro Pro Gly Pro Lys 995 1000 1005Gly Asn Pro Gly Leu Pro Gly Gln Pro Gly Leu Ile Gly Pro Pro 1010 1015 1020Gly Leu Lys Gly Thr Ile Gly Asp Met Gly Phe Pro Gly Pro Gln 1025 1030 1035Gly Val Glu Gly Pro Pro Gly Pro Ser Gly Val Pro Gly Gln Pro 1040 1045 1050Gly Ser Pro Gly Leu Pro Gly Gln Lys Gly Asp Lys Gly Asp Pro 1055 1060 1065Gly Ile Ser Ser Ile Gly Leu Pro Gly Leu Pro Gly Pro Lys Gly 1070 1075 1080Glu Pro Gly Leu Pro Gly Tyr Pro Gly Asn Pro Gly Ile Lys Gly 1085 1090 1095Ser Val Gly Asp Pro Gly Leu Pro Gly Leu Pro Gly Thr Pro Gly 1100 1105 1110Ala Lys Gly Gln Pro Gly Leu Pro Gly Phe Pro Gly Thr Pro Gly 1115 1120 1125Pro Pro Gly Pro Lys Gly Ile Ser Gly Pro Pro Gly Asn Pro Gly 1130 1135 1140Leu Pro Gly Glu Pro Gly Pro Val Gly Gly Gly Gly His Pro Gly 1145 1150 1155Gln Pro Gly Pro Pro Gly Glu Lys Gly Lys Pro Gly Gln Asp Gly 1160 1165 1170Ile Pro Gly Pro Ala Gly Gln Lys Gly Glu Pro Gly Gln Pro Gly 1175 1180 1185Phe Gly Asn Pro Gly Pro Pro Gly Leu Pro Gly Leu Ser Gly Gln 1190 1195 1200Lys Gly Asp Gly Gly Leu Pro Gly Ile Pro Gly Asn Pro Gly Leu 1205 1210 1215Pro Gly Pro Lys Gly Glu Pro Gly Phe His Gly Phe Pro Gly Val 1220 1225 1230Gln Gly Pro Pro Gly Pro Pro Gly Ser Pro Gly Pro Ala Leu Glu 1235 1240 1245Gly Pro Lys Gly Asn Pro Gly Pro Gln Gly Pro Pro Gly Arg Pro 1250 1255 1260Gly Leu Pro Gly Pro Glu Gly Pro Pro Gly Leu Pro Gly Asn Gly 1265 1270 1275Gly Ile Lys Gly Glu Lys Gly Asn Pro Gly Gln Pro Gly Leu Pro 1280 1285 1290Gly Leu Pro Gly Leu Lys Gly Asp Gln Gly Pro Pro Gly Leu Gln 1295 1300 1305Gly Asn Pro Gly Arg Pro Gly Leu Asn Gly Met Lys Gly Asp Pro 1310 1315 1320Gly Leu Pro Gly Val Pro Gly Phe Pro Gly Met Lys Gly Pro Ser 1325 1330 1335Gly Val Pro Gly Ser Ala Gly Pro Glu Gly Glu Pro Gly Leu Ile 1340 1345 1350Gly Pro Pro Gly Pro Pro Gly Leu Pro Gly Pro Ser Gly Gln Ser 1355 1360 1365Ile Ile Ile Lys Gly Asp Ala Gly Pro Pro Gly Ile Pro Gly Gln 1370 1375 1380Pro Gly Leu Lys Gly Leu Pro Gly Pro Gln Gly Pro Gln Gly Leu 1385 1390 1395Pro Gly Pro Thr Gly Pro Pro Gly Asp Pro Gly Arg Asn Gly Leu 1400 1405 1410Pro Gly Phe Asp Gly Ala Gly Gly Arg Lys Gly Asp Pro Gly Leu 1415 1420 1425Pro Gly Gln Pro Gly Thr Arg Gly Leu Asp Gly Pro Pro Gly Pro 1430 1435 1440Asp Gly Leu Gln Gly Pro Pro Gly Pro Pro Gly Thr Ser Ser Val 1445 1450 1455Ala His Gly Phe Leu Ile Thr Arg His Ser Gln Thr Thr Asp Ala 1460 1465 1470Pro Gln Cys Pro Gln Gly Thr Leu Gln Val Tyr Glu Gly Phe Ser 1475 1480 1485Leu Leu Tyr Val Gln Gly Asn Lys Arg Ala His Gly Gln Asp Leu 1490 1495 1500Gly Thr Ala Gly Ser Cys Leu Arg Arg Phe Ser Thr Met Pro Phe 1505 1510 1515Met Phe Cys Asn Ile Asn Asn Val Cys Asn Phe Ala Ser Arg Asn 1520 1525 1530Asp Tyr Ser Tyr Trp Leu Ser Thr Pro Glu Pro Met Pro Met Ser 1535 1540 1545Met Gln Pro Leu Lys Gly Gln Ser Ile Gln Pro Phe Ile Ser Arg 1550 1555 1560Cys Ala Val Cys Glu Ala Pro Ala Val Val Ile Ala Val His Ser 1565 1570 1575Gln Thr Ile Gln Ile Pro His Cys Pro Gln Gly Trp Asp Ser Leu 1580 1585 1590Trp Ile Gly Tyr Ser Phe Met Met His Thr Ser Ala Gly Ala Glu 1595 1600 1605Gly Ser Gly Gln Ala Leu Ala Ser Pro Gly Ser Cys Leu Glu Glu 1610 1615 1620Phe Arg Ser Ala Pro Phe Ile Glu Cys His Gly Arg Gly Thr Cys 1625 1630 1635Asn Tyr Tyr Ala Asn Ser Tyr Ser Phe Trp Leu Ala Thr Val Asp 1640 1645 1650Val Ser Asp Met Phe Ser Lys Pro Gln Ser Glu Thr Leu Lys Ala 1655 1660 1665Gly Asp Leu Arg Thr Arg Ile Ser Arg Cys Gln Val Cys Met Lys 1670 1675 1680Arg Thr 16858561PRTHomo sapiens 8Met Ala Phe Pro Leu Glu Glu Glu Ala Gly Arg Ile Lys Asp Cys Trp1 5 10 15Asp Asn Gln Glu Ala Pro Ala Leu Ser Thr Cys Ser Asn Ala Asn Ile 20 25 30Phe Arg Arg Ile Asn Ala Ile Leu Asp Asn Ser Leu Asp Phe Ser Arg 35 40 45Val Cys Thr Thr Pro Ile Asn Arg Gly Ile His Asp His Leu Pro Asp 50 55 60Phe Gln Asp Ser Glu Glu Thr Val Thr Ser Arg Met Leu Phe Pro Thr65 70 75 80Ser Ala Gln Glu Ser Ser Arg Gly Leu Pro Asp Ala Asn Asp Leu Cys 85 90 95Leu Gly Leu Gln Ser Leu Ser Leu Thr Gly Trp Asp Arg Pro Trp Ser 100 105 110Thr Gln Asp Ser Asp Ser Ser Ala Gln Ser Ser Thr His Ser Val Leu 115 120 125Ser Met Leu His Asn Pro Leu Gly Asn Val Leu Gly Lys Pro Pro Leu 130 135 140Ser Phe Leu Pro Leu Asp Pro Leu Gly Ser Asp Leu Val Asp Lys Phe145 150 155 160Pro Ala Pro Ser Val Arg Gly Ser Arg Leu Asp Thr Arg Pro Ile Leu 165 170 175Asp Ser Arg Ser Ser Ser Pro Ser Asp Ser Asp Thr Ser Gly Phe Ser 180 185 190Ser Gly Ser Asp His Leu Ser Asp Leu Ile Ser Ser Leu Arg Ile Ser 195 200 205Pro Pro Leu Pro Phe Leu Ser Leu Ser Gly Gly Gly Pro Arg Asp Pro 210 215 220Leu Lys Met Gly Val Gly Ser Arg Met Asp Gln Glu Gln Ala Ala Leu225 230 235 240Ala Ala Val Thr Pro Ser Pro Thr Ser Ala Ser Lys Arg Trp Pro Gly 245 250 255Ala Ser Val Trp Pro Ser Trp Asp Leu Leu Glu Ala Pro Lys Asp Pro 260 265 270Phe Ser Ile Glu Arg Glu Ala Arg Leu His Arg Gln Ala Ala Ala Val 275 280 285Asn Glu Ala Thr Cys Thr Trp Ser Gly Gln Leu Pro Pro Arg Asn Tyr 290 295 300Lys Asn Pro Ile Tyr Ser Cys Lys Val Phe Leu Gly Gly Val Pro Trp305 310 315 320Asp Ile Thr Glu Ala Gly Leu Val Asn Thr Phe Arg Val Phe Gly Ser 325 330 335Leu Ser Val Glu Trp Pro Gly Lys Asp Gly Lys His Pro Arg Cys Pro 340 345 350Pro Lys Gly Tyr Val Tyr Leu Val Phe Glu Leu Glu Lys Ser Val Arg 355 360 365Ser Leu Leu Gln Ala Cys Ser His Asp Pro Leu Ser Pro Asp Gly Leu 370 375 380Ser Glu Tyr Tyr Phe Lys Met Ser Ser Arg Arg Met Arg Cys Lys Glu385 390 395 400Val Gln Val Ile Pro Trp Val Leu Ala Asp Ser Asn Phe Val Arg Ser 405 410 415Pro Ser Gln Arg Leu Asp Pro Ser Arg Thr Val Phe Val Gly Ala Leu 420 425 430His Gly Met Leu Asn Ala Glu Ala Leu Ala Ala Ile Leu Asn Asp Leu 435 440 445Phe Gly Gly Val Val Tyr Ala Gly Ile Asp Thr Asp Lys His Lys Tyr 450 455 460Pro Ile Gly Ser Gly Arg Val Thr Phe Asn Asn Gln Arg Ser Tyr Leu465 470 475 480Lys Ala Val Ser Ala Ala Phe Val Glu Ile Lys Thr Thr Lys Phe Thr 485 490 495Lys Lys Val Gln Ile Asp Pro Tyr Leu Glu Asp Ser Leu Cys His Ile 500 505 510Cys Ser Ser Gln Pro Gly Pro Phe Phe Cys Arg Asp Gln Val Cys Phe 515 520 525Lys Tyr Phe Cys Arg Ser Cys Trp His Trp Arg His Ser Met Glu Gly 530 535 540Leu Arg His His Ser Pro Leu Met Arg Asn Gln Lys Asn Arg Asp Ser545 550 555 560Ser91255PRTHomo sapiens 9Met Glu Leu Ala Ala Leu Cys Arg Trp Gly Leu Leu Leu Ala Leu Leu1 5 10 15Pro Pro Gly Ala Ala Ser Thr Gln Val Cys Thr Gly Thr Asp Met Lys 20 25 30Leu Arg Leu Pro Ala Ser Pro Glu Thr His Leu Asp Met Leu Arg His 35 40 45Leu Tyr Gln Gly Cys Gln Val Val Gln Gly Asn Leu Glu Leu Thr Tyr 50 55 60Leu Pro Thr Asn Ala Ser Leu Ser Phe Leu Gln Asp Ile Gln Glu Val65 70 75 80Gln Gly Tyr Val Leu Ile Ala His Asn Gln Val Arg Gln Val Pro Leu 85 90 95Gln Arg Leu Arg Ile Val Arg Gly Thr Gln Leu Phe Glu Asp Asn Tyr 100 105 110Ala Leu Ala Val Leu Asp Asn Gly Asp Pro Leu Asn Asn Thr Thr Pro 115 120 125Val Thr Gly Ala Ser Pro Gly Gly Leu Arg Glu Leu Gln Leu Arg Ser 130 135 140Leu Thr Glu Ile Leu Lys Gly Gly Val Leu Ile Gln Arg Asn Pro Gln145 150 155 160Leu Cys Tyr Gln Asp Thr Ile Leu Trp Lys Asp Ile Phe His Lys Asn 165 170 175Asn Gln Leu Ala Leu Thr Leu Ile Asp Thr Asn Arg Ser Arg Ala Cys 180 185 190His Pro Cys Ser Pro Met Cys Lys Gly Ser Arg Cys Trp Gly Glu Ser 195 200 205Ser Glu Asp Cys Gln Ser Leu Thr Arg Thr Val Cys Ala Gly Gly Cys 210 215 220Ala Arg Cys Lys Gly Pro Leu Pro Thr Asp Cys Cys His Glu Gln Cys225 230 235 240Ala Ala Gly Cys Thr Gly Pro Lys His Ser Asp Cys Leu Ala Cys Leu 245 250 255His Phe Asn His Ser Gly Ile Cys Glu Leu His Cys Pro Ala Leu Val 260 265 270Thr Tyr Asn Thr Asp Thr Phe Glu Ser Met Pro Asn Pro Glu Gly Arg 275 280 285Tyr Thr Phe Gly Ala Ser Cys Val Thr Ala Cys Pro Tyr Asn Tyr Leu 290 295 300Ser Thr Asp Val Gly Ser Cys Thr Leu Val Cys Pro Leu His Asn Gln305 310 315 320Glu Val Thr Ala Glu Asp Gly Thr Gln Arg Cys Glu Lys Cys Ser Lys 325 330 335Pro Cys Ala Arg Val Cys Tyr Gly Leu Gly Met Glu His Leu Arg Glu 340 345 350Val Arg Ala Val Thr Ser Ala Asn Ile Gln Glu Phe Ala Gly Cys Lys 355 360 365Lys Ile Phe Gly Ser Leu Ala Phe Leu Pro Glu Ser Phe Asp Gly Asp 370 375 380Pro Ala Ser Asn Thr Ala Pro Leu Gln Pro Glu Gln Leu Gln Val Phe385 390 395 400Glu Thr Leu Glu Glu Ile Thr Gly Tyr Leu Tyr Ile Ser Ala Trp Pro 405 410 415Asp Ser Leu Pro Asp Leu Ser Val Phe Gln Asn Leu Gln Val Ile Arg 420 425 430Gly Arg Ile Leu His Asn Gly Ala Tyr Ser Leu Thr Leu Gln Gly Leu 435 440 445Gly Ile Ser Trp Leu Gly Leu Arg Ser Leu Arg Glu Leu Gly Ser Gly 450 455 460Leu Ala Leu Ile His His Asn Thr His Leu Cys Phe Val His Thr Val465 470 475 480Pro Trp Asp Gln Leu Phe Arg Asn Pro His Gln Ala Leu Leu His Thr 485 490 495Ala Asn Arg Pro Glu Asp Glu Cys Val Gly Glu Gly Leu Ala Cys His 500 505 510Gln Leu Cys Ala Arg Gly His Cys Trp Gly Pro Gly Pro Thr Gln Cys 515 520 525Val Asn Cys Ser Gln Phe Leu Arg Gly Gln Glu Cys Val Glu Glu Cys 530 535 540Arg Val Leu Gln Gly Leu Pro Arg Glu Tyr Val Asn Ala Arg His Cys545 550 555 560Leu Pro Cys His Pro Glu Cys Gln Pro Gln Asn Gly Ser Val Thr Cys 565 570 575Phe Gly Pro Glu Ala Asp Gln Cys Val Ala Cys Ala His Tyr Lys Asp 580 585 590Pro Pro Phe Cys Val Ala Arg Cys Pro Ser Gly Val Lys Pro Asp Leu 595 600 605Ser Tyr Met Pro Ile Trp Lys Phe Pro Asp Glu Glu Gly Ala Cys Gln 610 615 620Pro Cys Pro Ile Asn Cys Thr His Ser Cys Val Asp Leu Asp Asp Lys625 630 635 640Gly Cys Pro Ala Glu Gln Arg Ala Ser Pro Leu Thr Ser Ile Ile Ser 645 650 655Ala Val Val Gly Ile Leu Leu Val Val Val Leu Gly Val Val Phe Gly 660 665 670Ile Leu Ile Lys Arg Arg Gln Gln Lys Ile Arg Lys Tyr Thr Met Arg 675 680 685Arg Leu Leu Gln Glu Thr Glu Leu Val Glu Pro Leu Thr Pro Ser Gly 690 695 700Ala Met Pro Asn Gln Ala Gln Met Arg Ile Leu Lys Glu Thr Glu Leu705 710 715 720Arg Lys Val Lys Val Leu Gly Ser Gly Ala Phe Gly Thr Val Tyr Lys 725 730 735Gly Ile Trp Ile Pro Asp Gly Glu Asn Val Lys Ile Pro Val Ala Ile 740 745 750Lys Val Leu Arg Glu Asn Thr Ser Pro Lys Ala Asn Lys Glu Ile Leu 755 760 765Asp Glu Ala Tyr Val Met Ala Gly Val Gly Ser Pro Tyr Val Ser Arg 770 775 780Leu Leu Gly Ile Cys Leu Thr Ser Thr Val Gln Leu Val Thr Gln Leu785 790 795 800Met Pro Tyr Gly Cys Leu Leu Asp His Val Arg Glu Asn Arg Gly Arg 805 810 815Leu Gly Ser Gln Asp Leu Leu Asn Trp Cys Met Gln Ile Ala Lys Gly 820 825 830Met Ser Tyr Leu Glu Asp Val Arg Leu Val His Arg Asp Leu Ala Ala 835 840 845Arg Asn Val Leu Val Lys Ser Pro Asn His Val Lys Ile Thr Asp Phe 850 855 860Gly Leu Ala Arg Leu Leu Asp Ile Asp Glu Thr Glu Tyr His Ala Asp865 870 875 880Gly Gly Lys Val Pro Ile Lys Trp Met Ala Leu Glu Ser Ile Leu Arg 885 890 895Arg Arg Phe Thr His Gln Ser Asp Val Trp Ser Tyr Gly Val Thr Val 900 905 910Trp Glu Leu Met Thr Phe Gly Ala Lys Pro Tyr Asp Gly Ile Pro Ala 915 920 925Arg Glu Ile Pro Asp Leu Leu Glu Lys Gly Glu Arg Leu Pro Gln Pro 930 935 940Pro Ile Cys Thr Ile Asp Val Tyr Met Ile Met Val Lys Cys Trp Met945 950 955 960Ile Asp Ser Glu Cys Arg Pro Arg Phe Arg Glu Leu Val Ser Glu Phe 965 970 975Ser Arg Met Ala Arg Asp Pro Gln Arg Phe Val Val Ile Gln Asn Glu 980 985 990Asp Leu Gly Pro Ala Ser Pro Leu Asp Ser Thr Phe Tyr Arg Ser Leu 995 1000 1005Leu Glu Asp Asp Asp Met Gly Asp Leu Val Asp Ala Glu Glu Tyr 1010 1015 1020Leu Val Pro Gln Gln Gly Phe Phe Cys Pro Asp Pro Ala Pro Gly 1025 1030 1035Ala Gly Gly Met Val His His Arg His Arg Ser Ser Ser Thr Arg 1040 1045 1050Ser Gly Gly Gly Asp Leu Thr Leu Gly Leu Glu Pro Ser Glu Glu 1055 1060 1065Glu Ala Pro Arg Ser Pro Leu Ala Pro Ser Glu Gly Ala Gly Ser 1070 1075 1080Asp Val Phe Asp Gly Asp Leu Gly Met Gly Ala Ala Lys Gly Leu 1085 1090 1095Gln Ser Leu Pro Thr His Asp Pro Ser Pro Leu Gln Arg Tyr Ser 1100 1105 1110Glu Asp Pro Thr Val Pro Leu Pro Ser Glu Thr Asp Gly Tyr Val 1115 1120 1125Ala Pro Leu Thr Cys Ser Pro Gln Pro Glu Tyr Val Asn Gln Pro 1130 1135 1140Asp Val Arg Pro Gln Pro Pro Ser Pro Arg Glu Gly Pro Leu Pro 1145 1150 1155Ala Ala Arg Pro Ala Gly Ala Thr Leu Glu Arg Pro Lys Thr Leu 1160 1165 1170Ser Pro Gly Lys Asn Gly Val Val Lys Asp Val Phe Ala Phe Gly 1175 1180 1185Gly Ala Val Glu Asn Pro Glu Tyr Leu Thr Pro Gln Gly Gly Ala 1190 1195 1200Ala Pro Gln Pro His

Pro Pro Pro Ala Phe Ser Pro Ala Phe Asp 1205 1210 1215Asn Leu Tyr Tyr Trp Asp Gln Asp Pro Pro Glu Arg Gly Ala Pro 1220 1225 1230Pro Ser Thr Phe Lys Gly Thr Pro Thr Ala Glu Asn Pro Glu Tyr 1235 1240 1245Leu Gly Leu Asp Val Pro Val 1250 125510854PRTHomo sapiens 10Met Pro Pro Cys Ser Gly Gly Asp Gly Ser Thr Pro Pro Gly Pro Ser1 5 10 15Leu Arg Asp Arg Asp Cys Pro Ala Gln Ser Ala Glu Tyr Pro Arg Asp 20 25 30Arg Leu Asp Pro Arg Pro Gly Ser Pro Ser Glu Ala Ser Ser Pro Pro 35 40 45Phe Leu Arg Ser Arg Ala Pro Val Asn Trp Tyr Gln Glu Lys Ala Gln 50 55 60Val Phe Leu Trp His Leu Met Val Ser Gly Ser Thr Thr Leu Leu Cys65 70 75 80Leu Trp Lys Gln Pro Phe His Val Ser Ala Phe Pro Val Thr Ala Ser 85 90 95Leu Ala Phe Arg Gln Ser Gln Gly Ala Gly Gln His Leu Tyr Lys Asp 100 105 110Leu Gln Pro Phe Ile Leu Leu Arg Leu Leu Met Pro Glu Glu Thr Gln 115 120 125Thr Gln Asp Gln Pro Met Glu Glu Glu Glu Val Glu Thr Phe Ala Phe 130 135 140Gln Ala Glu Ile Ala Gln Leu Met Ser Leu Ile Ile Asn Thr Phe Tyr145 150 155 160Ser Asn Lys Glu Ile Phe Leu Arg Glu Leu Ile Ser Asn Ser Ser Asp 165 170 175Ala Leu Asp Lys Ile Arg Tyr Glu Ser Leu Thr Asp Pro Ser Lys Leu 180 185 190Asp Ser Gly Lys Glu Leu His Ile Asn Leu Ile Pro Asn Lys Gln Asp 195 200 205Arg Thr Leu Thr Ile Val Asp Thr Gly Ile Gly Met Thr Lys Ala Asp 210 215 220Leu Ile Asn Asn Leu Gly Thr Ile Ala Lys Ser Gly Thr Lys Ala Phe225 230 235 240Met Glu Ala Leu Gln Ala Gly Ala Asp Ile Ser Met Ile Gly Gln Phe 245 250 255Gly Val Gly Phe Tyr Ser Ala Tyr Leu Val Ala Glu Lys Val Thr Val 260 265 270Ile Thr Lys His Asn Asp Asp Glu Gln Tyr Ala Trp Glu Ser Ser Ala 275 280 285Gly Gly Ser Phe Thr Val Arg Thr Asp Thr Gly Glu Pro Met Gly Arg 290 295 300Gly Thr Lys Val Ile Leu His Leu Lys Glu Asp Gln Thr Glu Tyr Leu305 310 315 320Glu Glu Arg Arg Ile Lys Glu Ile Val Lys Lys His Ser Gln Phe Ile 325 330 335Gly Tyr Pro Ile Thr Leu Phe Val Glu Lys Glu Arg Asp Lys Glu Val 340 345 350Ser Asp Asp Glu Ala Glu Glu Lys Glu Asp Lys Glu Glu Glu Lys Glu 355 360 365Lys Glu Glu Lys Glu Ser Glu Asp Lys Pro Glu Ile Glu Asp Val Gly 370 375 380Ser Asp Glu Glu Glu Glu Lys Lys Asp Gly Asp Lys Lys Lys Lys Lys385 390 395 400Lys Ile Lys Glu Lys Tyr Ile Asp Gln Glu Glu Leu Asn Lys Thr Lys 405 410 415Pro Ile Trp Thr Arg Asn Pro Asp Asp Ile Thr Asn Glu Glu Tyr Gly 420 425 430Glu Phe Tyr Lys Ser Leu Thr Asn Asp Trp Glu Asp His Leu Ala Val 435 440 445Lys His Phe Ser Val Glu Gly Gln Leu Glu Phe Arg Ala Leu Leu Phe 450 455 460Val Pro Arg Arg Ala Pro Phe Asp Leu Phe Glu Asn Arg Lys Lys Lys465 470 475 480Asn Asn Ile Lys Leu Tyr Val Arg Arg Val Phe Ile Met Asp Asn Cys 485 490 495Glu Glu Leu Ile Pro Glu Tyr Leu Asn Phe Ile Arg Gly Val Val Asp 500 505 510Ser Glu Asp Leu Pro Leu Asn Ile Ser Arg Glu Met Leu Gln Gln Ser 515 520 525Lys Ile Leu Lys Val Ile Arg Lys Asn Leu Val Lys Lys Cys Leu Glu 530 535 540Leu Phe Thr Glu Leu Ala Glu Asp Lys Glu Asn Tyr Lys Lys Phe Tyr545 550 555 560Glu Gln Phe Ser Lys Asn Ile Lys Leu Gly Ile His Glu Asp Ser Gln 565 570 575Asn Arg Lys Lys Leu Ser Glu Leu Leu Arg Tyr Tyr Thr Ser Ala Ser 580 585 590Gly Asp Glu Met Val Ser Leu Lys Asp Tyr Cys Thr Arg Met Lys Glu 595 600 605Asn Gln Lys His Ile Tyr Tyr Ile Thr Gly Glu Thr Lys Asp Gln Val 610 615 620Ala Asn Ser Ala Phe Val Glu Arg Leu Arg Lys His Gly Leu Glu Val625 630 635 640Ile Tyr Met Ile Glu Pro Ile Asp Glu Tyr Cys Val Gln Gln Leu Lys 645 650 655Glu Phe Glu Gly Lys Thr Leu Val Ser Val Thr Lys Glu Gly Leu Glu 660 665 670Leu Pro Glu Asp Glu Glu Glu Lys Lys Lys Gln Glu Glu Lys Lys Thr 675 680 685Lys Phe Glu Asn Leu Cys Lys Ile Met Lys Asp Ile Leu Glu Lys Lys 690 695 700Val Glu Lys Val Val Val Ser Asn Arg Leu Val Thr Ser Pro Cys Cys705 710 715 720Ile Val Thr Ser Thr Tyr Gly Trp Thr Ala Asn Met Glu Arg Ile Met 725 730 735Lys Ala Gln Ala Leu Arg Asp Asn Ser Thr Met Gly Tyr Met Ala Ala 740 745 750Lys Lys His Leu Glu Ile Asn Pro Asp His Ser Ile Ile Glu Thr Leu 755 760 765Arg Gln Lys Ala Glu Ala Asp Lys Asn Asp Lys Ser Val Lys Asp Leu 770 775 780Val Ile Leu Leu Tyr Glu Thr Ala Leu Leu Ser Ser Gly Phe Ser Leu785 790 795 800Glu Asp Pro Gln Thr His Ala Asn Arg Ile Tyr Arg Met Ile Lys Leu 805 810 815Gly Leu Gly Ile Asp Glu Asp Asp Pro Thr Ala Asp Asp Thr Ser Ala 820 825 830Ala Val Thr Glu Glu Met Pro Pro Leu Glu Gly Asp Asp Asp Thr Ser 835 840 845Arg Met Glu Glu Val Asp 85011712PRTHomo sapiens 11Met Ala Gly Gly Pro Gly Pro Gly Glu Pro Ala Ala Pro Gly Ala Gln1 5 10 15His Phe Leu Tyr Glu Val Pro Pro Trp Val Met Cys Arg Phe Tyr Lys 20 25 30Val Met Asp Ala Leu Glu Pro Ala Asp Trp Cys Gln Phe Ala Ala Leu 35 40 45Ile Val Arg Asp Gln Thr Glu Leu Arg Leu Cys Glu Arg Ser Gly Gln 50 55 60Arg Thr Ala Ser Val Leu Trp Pro Trp Ile Asn Arg Asn Ala Arg Val65 70 75 80Ala Asp Leu Val His Ile Leu Thr His Leu Gln Leu Leu Arg Ala Arg 85 90 95Asp Ile Ile Thr Ala Trp His Pro Pro Ala Pro Leu Pro Ser Pro Gly 100 105 110Thr Thr Ala Pro Arg Pro Ser Ser Ile Pro Ala Pro Ala Glu Ala Glu 115 120 125Ala Trp Ser Pro Arg Lys Leu Pro Ser Ser Ala Ser Thr Phe Leu Ser 130 135 140Pro Ala Phe Pro Gly Ser Gln Thr His Ser Gly Pro Glu Leu Gly Leu145 150 155 160Val Pro Ser Pro Ala Ser Leu Trp Pro Pro Pro Pro Ser Pro Ala Pro 165 170 175Ser Ser Thr Lys Pro Gly Pro Glu Ser Ser Val Ser Leu Leu Gln Gly 180 185 190Ala Arg Pro Phe Pro Phe Cys Trp Pro Leu Cys Glu Ile Ser Arg Gly 195 200 205Thr His Asn Phe Ser Glu Glu Leu Lys Ile Gly Glu Gly Gly Phe Gly 210 215 220Cys Val Tyr Arg Ala Val Met Arg Asn Thr Val Tyr Ala Val Lys Arg225 230 235 240Leu Lys Glu Asn Ala Asp Leu Glu Trp Thr Ala Val Lys Gln Ser Phe 245 250 255Leu Thr Glu Val Glu Gln Leu Ser Arg Phe Arg His Pro Asn Ile Val 260 265 270Asp Phe Ala Gly Tyr Cys Ala Gln Asn Gly Phe Tyr Cys Leu Val Tyr 275 280 285Gly Phe Leu Pro Asn Gly Ser Leu Glu Asp Arg Leu His Cys Gln Thr 290 295 300Gln Ala Cys Pro Pro Leu Ser Trp Pro Gln Arg Leu Asp Ile Leu Leu305 310 315 320Gly Thr Ala Arg Ala Ile Gln Phe Leu His Gln Asp Ser Pro Ser Leu 325 330 335Ile His Gly Asp Ile Lys Ser Ser Asn Val Leu Leu Asp Glu Arg Leu 340 345 350Thr Pro Lys Leu Gly Asp Phe Gly Leu Ala Arg Phe Ser Arg Phe Ala 355 360 365Gly Ser Ser Pro Ser Gln Ser Ser Met Val Ala Arg Thr Gln Thr Val 370 375 380Arg Gly Thr Leu Ala Tyr Leu Pro Glu Glu Tyr Ile Lys Thr Gly Arg385 390 395 400Leu Ala Val Asp Thr Asp Thr Phe Ser Phe Gly Val Val Val Leu Glu 405 410 415Thr Leu Ala Gly Gln Arg Ala Val Lys Thr His Gly Ala Arg Thr Lys 420 425 430Tyr Leu Lys Asp Leu Val Glu Glu Glu Ala Glu Glu Ala Gly Val Ala 435 440 445Leu Arg Ser Thr Gln Ser Thr Leu Gln Ala Gly Leu Ala Ala Asp Ala 450 455 460Trp Ala Ala Pro Ile Ala Met Gln Ile Tyr Lys Lys His Leu Asp Pro465 470 475 480Arg Pro Gly Pro Cys Pro Pro Glu Leu Gly Leu Gly Leu Gly Gln Leu 485 490 495Ala Cys Cys Cys Leu His Arg Arg Ala Lys Arg Arg Pro Pro Met Thr 500 505 510Gln Val Tyr Glu Arg Leu Glu Lys Leu Gln Ala Val Val Ala Gly Val 515 520 525Pro Gly His Ser Glu Ala Ala Ser Cys Ile Pro Pro Ser Pro Gln Glu 530 535 540Asn Ser Tyr Val Ser Ser Thr Gly Arg Ala His Ser Gly Ala Ala Pro545 550 555 560Trp Gln Pro Leu Ala Ala Pro Ser Gly Ala Ser Ala Gln Ala Ala Glu 565 570 575Gln Leu Gln Arg Gly Pro Asn Gln Pro Val Glu Ser Asp Glu Ser Leu 580 585 590Gly Gly Leu Ser Ala Ala Leu Arg Ser Trp His Leu Thr Pro Ser Cys 595 600 605Pro Leu Asp Pro Ala Pro Leu Arg Glu Ala Gly Cys Pro Gln Gly Asp 610 615 620Thr Ala Gly Glu Ser Ser Trp Gly Ser Gly Pro Gly Ser Arg Pro Thr625 630 635 640Ala Val Glu Gly Leu Ala Leu Gly Ser Ser Ala Ser Ser Ser Ser Glu 645 650 655Pro Pro Gln Ile Ile Ile Asn Pro Ala Arg Gln Lys Met Val Gln Lys 660 665 670Leu Ala Leu Tyr Glu Asp Gly Ala Leu Asp Ser Leu Gln Leu Leu Ser 675 680 685Ser Ser Ser Leu Pro Gly Leu Gly Leu Glu Gln Asp Arg Gln Gly Pro 690 695 700Glu Glu Ser Asp Glu Phe Gln Ser705 710121560PRTHomo sapiens 12Met Glu Pro Gly Ser Asp Asp Phe Leu Pro Pro Pro Glu Cys Pro Val1 5 10 15Phe Glu Pro Ser Trp Ala Glu Phe Arg Asp Pro Leu Gly Tyr Ile Ala 20 25 30Lys Ile Arg Pro Ile Ala Glu Lys Ser Gly Ile Cys Lys Ile Arg Pro 35 40 45Pro Ala Asp Trp Gln Pro Pro Phe Ala Val Glu Val Asp Asn Phe Arg 50 55 60Phe Thr Pro Arg Ile Gln Arg Leu Asn Glu Leu Glu Ala Gln Thr Arg65 70 75 80Val Lys Leu Asn Tyr Leu Asp Gln Ile Ala Lys Phe Trp Glu Ile Gln 85 90 95Gly Ser Ser Leu Lys Ile Pro Asn Val Glu Arg Arg Ile Leu Asp Leu 100 105 110Tyr Ser Leu Ser Lys Ile Val Val Glu Glu Gly Gly Tyr Glu Ala Ile 115 120 125Cys Lys Asp Arg Arg Trp Ala Arg Val Ala Gln Arg Leu Asn Tyr Pro 130 135 140Pro Gly Lys Asn Ile Gly Ser Leu Leu Arg Ser His Tyr Glu Arg Ile145 150 155 160Val Tyr Pro Tyr Glu Met Tyr Gln Ser Gly Ala Asn Leu Val Gln Cys 165 170 175Asn Thr Arg Pro Phe Asp Asn Glu Glu Lys Asp Lys Glu Tyr Lys Pro 180 185 190His Ser Ile Pro Leu Arg Gln Ser Val Gln Pro Ser Lys Phe Asn Ser 195 200 205Tyr Gly Arg Arg Ala Lys Arg Leu Gln Pro Asp Pro Glu Pro Thr Glu 210 215 220Glu Asp Ile Glu Lys Asn Pro Glu Leu Lys Lys Leu Gln Ile Tyr Gly225 230 235 240Ala Gly Pro Lys Met Met Gly Leu Gly Leu Met Ala Lys Asp Lys Thr 245 250 255Leu Arg Lys Lys Asp Lys Glu Gly Pro Glu Cys Pro Pro Thr Val Val 260 265 270Val Lys Glu Glu Leu Gly Gly Asp Val Lys Val Glu Ser Thr Ser Pro 275 280 285Lys Thr Phe Leu Glu Ser Lys Glu Glu Leu Ser His Ser Pro Glu Pro 290 295 300Cys Thr Lys Met Thr Met Arg Leu Arg Arg Asn His Ser Asn Ala Gln305 310 315 320Phe Ile Glu Ser Tyr Val Cys Arg Met Cys Ser Arg Gly Asp Glu Asp 325 330 335Asp Lys Leu Leu Leu Cys Asp Gly Cys Asp Asp Asn Tyr His Ile Phe 340 345 350Cys Leu Leu Pro Pro Leu Pro Glu Ile Pro Lys Gly Val Trp Arg Cys 355 360 365Pro Lys Cys Val Met Ala Glu Cys Lys Arg Pro Pro Glu Ala Phe Gly 370 375 380Phe Glu Gln Ala Thr Arg Glu Tyr Thr Leu Gln Ser Phe Gly Glu Met385 390 395 400Ala Asp Ser Phe Lys Ala Asp Tyr Phe Asn Met Pro Val His Met Val 405 410 415Pro Thr Glu Leu Val Glu Lys Glu Phe Trp Arg Leu Val Asn Ser Ile 420 425 430Glu Glu Asp Val Thr Val Glu Tyr Gly Ala Asp Ile His Ser Lys Glu 435 440 445Phe Gly Ser Gly Phe Pro Val Ser Asp Ser Lys Arg His Leu Thr Pro 450 455 460Glu Glu Glu Glu Tyr Ala Thr Ser Gly Trp Asn Leu Asn Val Met Pro465 470 475 480Val Leu Glu Gln Ser Val Leu Cys His Ile Asn Ala Asp Ile Ser Gly 485 490 495Met Lys Val Pro Trp Leu Tyr Val Gly Met Val Phe Ser Ala Phe Cys 500 505 510Trp His Ile Glu Asp His Trp Ser Tyr Ser Ile Asn Tyr Leu His Trp 515 520 525Gly Glu Pro Lys Thr Trp Tyr Gly Val Pro Ser Leu Ala Ala Glu His 530 535 540Leu Glu Glu Val Met Lys Lys Leu Thr Pro Glu Leu Phe Asp Ser Gln545 550 555 560Pro Asp Leu Leu His Gln Leu Val Thr Leu Met Asn Pro Asn Thr Leu 565 570 575Met Ser His Gly Val Pro Val Val Arg Thr Asn Gln Cys Ala Gly Glu 580 585 590Phe Val Ile Thr Phe Pro Arg Ala Tyr His Ser Gly Phe Asn Gln Gly 595 600 605Tyr Asn Phe Ala Glu Ala Val Asn Phe Cys Thr Ala Asp Trp Leu Pro 610 615 620Ala Gly Arg Gln Cys Ile Glu His Tyr Arg Arg Leu Arg Arg Tyr Cys625 630 635 640Val Phe Ser His Glu Glu Leu Ile Cys Lys Met Ala Ala Cys Pro Glu 645 650 655Lys Leu Asp Leu Asn Leu Ala Ala Ala Val His Lys Glu Met Phe Ile 660 665 670Met Val Gln Glu Glu Arg Arg Leu Arg Lys Ala Leu Leu Glu Lys Gly 675 680 685Ile Thr Glu Ala Glu Arg Glu Ala Phe Glu Leu Leu Pro Asp Asp Glu 690 695 700Arg Gln Cys Ile Lys Cys Lys Thr Thr Cys Phe Leu Ser Ala Leu Ala705 710 715 720Cys Tyr Asp Cys Pro Asp Gly Leu Val Cys Leu Ser His Ile Asn Asp 725 730 735Leu Cys Lys Cys Ser Ser Ser Arg Gln Tyr Leu Arg Tyr Arg Tyr Thr 740 745 750Leu Asp Glu Leu Pro Ala Met Leu His Lys Leu Lys Val Arg Ala Glu 755 760 765Ser Phe Asp Thr Trp Ala Asn Lys Val Arg Val Ala Leu Glu Val Glu 770 775 780Asp Gly Arg Lys Arg Ser Leu Glu Glu Leu Arg Ala Leu Glu Ser Glu785 790 795 800Ala Arg Glu Arg Arg Phe Pro Asn Ser Glu Leu Leu Gln Gln Leu Lys 805 810 815Asn Cys Leu Ser Glu Ala Glu Ala Cys Val Ser Arg Ala Leu Gly Leu 820 825 830Val Ser Gly Gln Glu Ala Gly Pro His Arg Val Ala Gly Leu Gln Met 835 840 845Thr Leu Thr Glu Leu Arg Ala

Phe Leu Asp Gln Met Asn Asn Leu Pro 850 855 860Cys Ala Met His Gln Ile Gly Asp Val Lys Gly Val Leu Glu Gln Val865 870 875 880Glu Ala Tyr Gln Ala Glu Ala Arg Glu Ala Leu Ala Ser Leu Pro Ser 885 890 895Ser Pro Gly Leu Leu Gln Ser Leu Leu Glu Arg Gly Arg Gln Leu Gly 900 905 910Val Glu Val Pro Glu Ala Gln Gln Leu Gln Arg Gln Val Glu Gln Ala 915 920 925Arg Trp Leu Asp Glu Val Lys Arg Thr Leu Ala Pro Ser Ala Arg Arg 930 935 940Gly Thr Leu Ala Val Met Arg Gly Leu Leu Val Ala Gly Ala Ser Val945 950 955 960Ala Pro Ser Pro Ala Val Asp Lys Ala Gln Ala Glu Leu Gln Glu Leu 965 970 975Leu Thr Ile Ala Glu Arg Trp Glu Glu Lys Ala His Leu Cys Leu Glu 980 985 990Ala Arg Gln Lys His Pro Pro Ala Thr Leu Glu Ala Ile Ile Arg Glu 995 1000 1005Ala Glu Asn Ile Pro Val His Leu Pro Asn Ile Gln Ala Leu Lys 1010 1015 1020Glu Ala Leu Ala Lys Ala Arg Ala Trp Ile Ala Asp Val Asp Glu 1025 1030 1035Ile Gln Asn Gly Asp His Tyr Pro Cys Leu Asp Asp Leu Glu Gly 1040 1045 1050Leu Val Ala Val Gly Arg Asp Leu Pro Val Gly Leu Glu Glu Leu 1055 1060 1065Arg Gln Leu Glu Leu Gln Val Leu Thr Ala His Ser Trp Arg Glu 1070 1075 1080Lys Ala Ser Lys Thr Phe Leu Lys Lys Asn Ser Cys Tyr Thr Leu 1085 1090 1095Leu Glu Val Leu Cys Pro Cys Ala Asp Ala Gly Ser Asp Ser Thr 1100 1105 1110Lys Arg Ser Arg Trp Met Glu Lys Glu Leu Gly Leu Tyr Lys Ser 1115 1120 1125Asp Thr Glu Leu Leu Gly Leu Ser Ala Gln Asp Leu Arg Asp Pro 1130 1135 1140Gly Ser Val Ile Val Ala Phe Lys Glu Gly Glu Gln Lys Glu Lys 1145 1150 1155Glu Gly Ile Leu Gln Leu Arg Arg Thr Asn Ser Ala Lys Pro Ser 1160 1165 1170Pro Leu Ala Ser Ser Ser Thr Ala Ser Ser Thr Thr Ser Ile Cys 1175 1180 1185Val Cys Gly Gln Val Leu Ala Gly Ala Gly Ala Leu Gln Cys Asp 1190 1195 1200Leu Cys Gln Asp Trp Phe His Gly Arg Cys Val Ser Val Pro Arg 1205 1210 1215Leu Leu Ser Ser Pro Arg Pro Asn Pro Thr Ser Ser Pro Leu Leu 1220 1225 1230Ala Trp Trp Glu Trp Asp Thr Lys Phe Leu Cys Pro Leu Cys Met 1235 1240 1245Arg Ser Arg Arg Pro Arg Leu Glu Thr Ile Leu Ala Leu Leu Val 1250 1255 1260Ala Leu Gln Arg Leu Pro Val Arg Leu Pro Glu Gly Glu Ala Leu 1265 1270 1275Gln Cys Leu Thr Glu Arg Ala Ile Ser Trp Gln Gly Arg Ala Arg 1280 1285 1290Gln Ala Leu Ala Ser Glu Asp Val Thr Ala Leu Leu Gly Arg Leu 1295 1300 1305Ala Glu Leu Arg Gln Arg Leu Gln Ala Glu Pro Arg Pro Glu Glu 1310 1315 1320Pro Pro Asn Tyr Pro Ala Ala Pro Ala Ser Asp Pro Leu Arg Glu 1325 1330 1335Gly Ser Gly Lys Asp Met Pro Lys Val Gln Gly Leu Leu Glu Asn 1340 1345 1350Gly Asp Ser Val Thr Ser Pro Glu Lys Val Ala Pro Glu Glu Gly 1355 1360 1365Ser Gly Lys Arg Asp Leu Glu Leu Leu Ser Ser Leu Leu Pro Gln 1370 1375 1380Leu Thr Gly Pro Val Leu Glu Leu Pro Glu Ala Thr Arg Ala Pro 1385 1390 1395Leu Glu Glu Leu Met Met Glu Gly Asp Leu Leu Glu Val Thr Leu 1400 1405 1410Asp Glu Asn His Ser Ile Trp Gln Leu Leu Gln Ala Gly Gln Pro 1415 1420 1425Pro Asp Leu Glu Arg Ile Arg Thr Leu Leu Glu Leu Glu Lys Ala 1430 1435 1440Glu Arg His Gly Ser Arg Ala Arg Gly Arg Ala Leu Glu Arg Arg 1445 1450 1455Arg Arg Arg Lys Val Asp Arg Gly Gly Glu Gly Asp Asp Pro Ala 1460 1465 1470Arg Glu Glu Leu Glu Pro Lys Arg Val Arg Ser Ser Gly Pro Glu 1475 1480 1485Ala Glu Glu Val Gln Glu Glu Glu Glu Leu Glu Glu Glu Thr Gly 1490 1495 1500Gly Glu Gly Pro Pro Ala Pro Ile Pro Thr Thr Gly Ser Pro Ser 1505 1510 1515Thr Gln Glu Asn Gln Asn Gly Leu Glu Pro Ala Glu Gly Thr Thr 1520 1525 1530Ser Gly Pro Ser Ala Pro Phe Ser Thr Leu Thr Pro Arg Leu His 1535 1540 1545Leu Pro Cys Pro Gln Gln Pro Pro Gln Gln Gln Leu 1550 1555 1560131401PRTHomo sapiens 13Met Lys Ser Cys Gly Val Ser Leu Ala Thr Ala Ala Ala Ala Ala Ala1 5 10 15Ala Phe Gly Asp Glu Glu Lys Lys Met Ala Ala Gly Lys Ala Ser Gly 20 25 30Glu Ser Glu Glu Ala Ser Pro Ser Leu Thr Ala Glu Glu Arg Glu Ala 35 40 45Leu Gly Gly Leu Asp Ser Arg Leu Phe Gly Phe Val Arg Phe His Glu 50 55 60Asp Gly Ala Arg Thr Lys Ala Leu Leu Gly Lys Ala Val Arg Cys Tyr65 70 75 80Glu Ser Leu Ile Leu Lys Ala Glu Gly Lys Val Glu Ser Asp Phe Phe 85 90 95Cys Gln Leu Gly His Phe Asn Leu Leu Leu Glu Asp Tyr Pro Lys Ala 100 105 110Leu Ser Ala Tyr Gln Arg Tyr Tyr Ser Leu Gln Ser Asp Tyr Trp Lys 115 120 125Asn Ala Ala Phe Leu Tyr Gly Leu Gly Leu Val Tyr Phe His Tyr Asn 130 135 140Ala Phe Gln Trp Ala Ile Lys Ala Phe Gln Glu Val Leu Tyr Val Asp145 150 155 160Pro Ser Phe Cys Arg Ala Lys Glu Ile His Leu Arg Leu Gly Leu Met 165 170 175Phe Lys Val Asn Thr Asp Tyr Glu Ser Ser Leu Lys His Phe Gln Leu 180 185 190Ala Leu Val Asp Cys Asn Pro Cys Thr Leu Ser Asn Ala Glu Ile Gln 195 200 205Phe His Ile Ala His Leu Tyr Glu Thr Gln Arg Lys Tyr His Ser Ala 210 215 220Lys Glu Ala Tyr Glu Gln Leu Leu Gln Thr Glu Asn Leu Ser Ala Gln225 230 235 240Val Lys Ala Thr Val Leu Gln Gln Leu Gly Trp Met His His Thr Val 245 250 255Asp Leu Leu Gly Asp Lys Ala Thr Lys Glu Ser Tyr Ala Ile Gln Tyr 260 265 270Leu Gln Lys Ser Leu Glu Ala Asp Pro Asn Ser Gly Gln Ser Trp Tyr 275 280 285Phe Leu Gly Arg Cys Tyr Ser Ser Ile Gly Lys Val Gln Asp Ala Phe 290 295 300Ile Ser Tyr Arg Gln Ser Ile Asp Lys Ser Glu Ala Ser Ala Asp Thr305 310 315 320Trp Cys Ser Ile Gly Val Leu Tyr Gln Gln Gln Asn Gln Pro Met Asp 325 330 335Ala Leu Gln Ala Tyr Ile Cys Ala Val Gln Leu Asp His Gly His Ala 340 345 350Ala Ala Trp Met Asp Leu Gly Thr Leu Tyr Glu Ser Cys Asn Gln Pro 355 360 365Gln Asp Ala Ile Lys Cys Tyr Leu Asn Ala Thr Arg Ser Lys Ser Cys 370 375 380Ser Asn Thr Ser Ala Leu Ala Ala Arg Ile Lys Tyr Leu Gln Ala Gln385 390 395 400Leu Cys Asn Leu Pro Gln Gly Ser Leu Gln Asn Lys Thr Lys Leu Leu 405 410 415Pro Ser Ile Glu Glu Ala Trp Ser Leu Pro Ile Pro Ala Glu Leu Thr 420 425 430Ser Arg Gln Gly Ala Met Asn Thr Ala Gln Gln Asn Thr Ser Asp Asn 435 440 445Trp Ser Gly Gly His Ala Val Ser His Pro Pro Val Gln Gln Gln Ala 450 455 460His Ser Trp Cys Leu Thr Pro Gln Lys Leu Gln His Leu Glu Gln Leu465 470 475 480Arg Ala Asn Arg Asn Asn Leu Asn Pro Ala Gln Lys Leu Met Leu Glu 485 490 495Gln Leu Glu Ser Gln Phe Val Leu Met Gln Gln His Gln Met Arg Pro 500 505 510Thr Gly Val Ala Gln Val Arg Ser Thr Gly Ile Pro Asn Gly Pro Thr 515 520 525Ala Asp Ser Ser Leu Pro Thr Asn Ser Val Ser Gly Gln Gln Pro Gln 530 535 540Leu Ala Leu Thr Arg Val Pro Ser Val Ser Gln Pro Gly Val Arg Pro545 550 555 560Ala Cys Pro Gly Gln Pro Leu Ala Asn Gly Pro Phe Ser Ala Gly His 565 570 575Val Pro Cys Ser Thr Ser Arg Thr Leu Gly Ser Thr Asp Thr Ile Leu 580 585 590Ile Gly Asn Asn His Ile Thr Gly Ser Gly Ser Asn Gly Asn Val Pro 595 600 605Tyr Leu Gln Arg Asn Ala Leu Thr Leu Pro His Asn Arg Thr Asn Leu 610 615 620Thr Ser Ser Ala Glu Glu Pro Trp Lys Asn Gln Leu Ser Asn Ser Thr625 630 635 640Gln Gly Leu His Lys Gly Gln Ser Ser His Ser Ala Gly Pro Asn Gly 645 650 655Glu Arg Pro Leu Ser Ser Thr Gly Pro Ser Gln His Leu Gln Ala Ala 660 665 670Gly Ser Gly Ile Gln Asn Gln Asn Gly His Pro Thr Leu Pro Ser Asn 675 680 685Ser Val Thr Gln Gly Ala Ala Leu Asn His Leu Ser Ser His Thr Ala 690 695 700Thr Ser Gly Gly Gln Gln Gly Ile Thr Leu Thr Lys Glu Ser Lys Pro705 710 715 720Ser Gly Asn Ile Leu Thr Val Pro Glu Thr Ser Arg His Thr Gly Glu 725 730 735Thr Pro Asn Ser Thr Ala Ser Val Glu Gly Leu Pro Asn His Val His 740 745 750Gln Met Thr Ala Asp Ala Val Cys Ser Pro Ser His Gly Asp Ser Lys 755 760 765Ser Pro Gly Leu Leu Ser Ser Asp Asn Pro Gln Leu Ser Ala Leu Leu 770 775 780Met Gly Lys Ala Asn Asn Asn Val Gly Thr Gly Thr Cys Asp Lys Val785 790 795 800Asn Asn Ile His Pro Ala Val His Thr Lys Thr Asp Asn Ser Val Ala 805 810 815Ser Ser Pro Ser Ser Ala Ile Ser Thr Ala Thr Pro Ser Pro Lys Ser 820 825 830Thr Glu Gln Thr Thr Thr Asn Ser Val Thr Ser Leu Asn Ser Pro His 835 840 845Ser Gly Leu His Thr Ile Asn Gly Glu Gly Met Glu Glu Ser Gln Ser 850 855 860Pro Met Lys Thr Asp Leu Leu Leu Val Asn His Lys Pro Ser Pro Gln865 870 875 880Ile Ile Pro Ser Met Ser Val Ser Ile Tyr Pro Ser Ser Ala Glu Val 885 890 895Leu Lys Ala Cys Arg Asn Leu Gly Lys Asn Gly Leu Ser Asn Ser Ser 900 905 910Ile Leu Leu Asp Lys Cys Pro Pro Pro Arg Pro Pro Ser Ser Pro Tyr 915 920 925Pro Pro Leu Pro Lys Asp Lys Leu Asn Pro Pro Thr Pro Ser Ile Tyr 930 935 940Leu Glu Asn Lys Arg Asp Ala Phe Phe Pro Pro Leu His Gln Phe Cys945 950 955 960Thr Asn Pro Asn Asn Pro Val Thr Val Ile Arg Gly Leu Ala Gly Ala 965 970 975Leu Lys Leu Asp Leu Gly Leu Phe Ser Thr Lys Thr Leu Val Glu Ala 980 985 990Asn Asn Glu His Met Val Glu Val Arg Thr Gln Leu Leu Gln Pro Ala 995 1000 1005Asp Glu Asn Trp Asp Pro Thr Gly Thr Lys Lys Ile Trp His Cys 1010 1015 1020Glu Ser Asn Arg Ser His Thr Thr Ile Ala Lys Tyr Ala Gln Tyr 1025 1030 1035Gln Ala Ser Ser Phe Gln Glu Ser Leu Arg Glu Glu Asn Glu Lys 1040 1045 1050Arg Ser His His Lys Asp His Ser Asp Ser Glu Ser Thr Ser Ser 1055 1060 1065Asp Asn Ser Gly Arg Arg Arg Lys Gly Pro Phe Lys Thr Ile Lys 1070 1075 1080Phe Gly Thr Asn Ile Asp Leu Ser Asp Asp Lys Lys Trp Lys Leu 1085 1090 1095Gln Leu His Glu Leu Thr Lys Leu Pro Ala Phe Val Arg Val Val 1100 1105 1110Ser Ala Gly Asn Leu Leu Ser His Val Gly His Thr Ile Leu Gly 1115 1120 1125Met Asn Thr Val Gln Leu Tyr Met Lys Val Pro Gly Ser Arg Thr 1130 1135 1140Pro Gly His Gln Glu Asn Asn Asn Phe Cys Ser Val Asn Ile Asn 1145 1150 1155Ile Gly Pro Gly Asp Cys Glu Trp Phe Val Val Pro Glu Gly Tyr 1160 1165 1170Trp Gly Val Leu Asn Asp Phe Cys Glu Lys Asn Asn Leu Asn Phe 1175 1180 1185Leu Met Gly Ser Trp Trp Pro Asn Leu Glu Asp Leu Tyr Glu Ala 1190 1195 1200Asn Val Pro Val Tyr Arg Phe Ile Gln Arg Pro Gly Asp Leu Val 1205 1210 1215Trp Ile Asn Ala Gly Thr Val His Trp Val Gln Ala Ile Gly Trp 1220 1225 1230Cys Asn Asn Ile Ala Trp Asn Val Gly Pro Leu Thr Ala Cys Gln 1235 1240 1245Tyr Lys Leu Ala Val Glu Arg Tyr Glu Trp Asn Lys Leu Gln Ser 1250 1255 1260Val Lys Ser Ile Val Pro Met Val His Leu Ser Trp Asn Met Ala 1265 1270 1275Arg Asn Ile Lys Val Ser Asp Pro Lys Leu Phe Glu Met Ile Lys 1280 1285 1290Tyr Cys Leu Leu Arg Thr Leu Lys Gln Cys Gln Thr Leu Arg Glu 1295 1300 1305Ala Leu Ile Ala Ala Gly Lys Glu Ile Ile Trp His Gly Arg Thr 1310 1315 1320Lys Glu Glu Pro Ala His Tyr Cys Ser Ile Cys Glu Val Glu Val 1325 1330 1335Phe Asp Leu Leu Phe Val Thr Asn Glu Ser Asn Ser Arg Lys Thr 1340 1345 1350Tyr Ile Val His Cys Gln Asp Cys Ala Arg Lys Thr Ser Gly Asn 1355 1360 1365Leu Glu Asn Phe Val Val Leu Glu Gln Tyr Lys Met Glu Asp Leu 1370 1375 1380Met Gln Val Tyr Asp Gln Phe Thr Leu Ala Pro Pro Leu Pro Ser 1385 1390 1395Ala Ser Ser 140014859PRTHomo sapiens 14Met Ala Cys Arg Trp Ser Thr Lys Glu Ser Pro Arg Trp Arg Ser Ala1 5 10 15Leu Leu Leu Leu Phe Leu Ala Gly Val Tyr Gly Asn Gly Ala Leu Ala 20 25 30Glu His Ser Glu Asn Val His Ile Ser Gly Val Ser Thr Ala Cys Gly 35 40 45Glu Thr Pro Glu Gln Ile Arg Ala Pro Ser Gly Ile Ile Thr Ser Pro 50 55 60Gly Trp Pro Ser Glu Tyr Pro Ala Lys Ile Asn Cys Ser Trp Phe Ile65 70 75 80Arg Ala Asn Pro Gly Glu Ile Ile Thr Ile Ser Phe Gln Asp Phe Asp 85 90 95Ile Gln Gly Ser Arg Arg Cys Asn Leu Asp Trp Leu Thr Ile Glu Thr 100 105 110Tyr Lys Asn Ile Glu Ser Tyr Arg Ala Cys Gly Ser Thr Ile Pro Pro 115 120 125Pro Tyr Ile Ser Ser Gln Asp His Ile Trp Ile Arg Phe His Ser Asp 130 135 140Asp Asn Ile Ser Arg Lys Gly Phe Arg Leu Ala Tyr Phe Ser Gly Lys145 150 155 160Ser Glu Glu Pro Asn Cys Ala Cys Asp Gln Phe Arg Cys Gly Asn Gly 165 170 175Lys Cys Ile Pro Glu Ala Trp Lys Cys Asn Asn Met Asp Glu Cys Gly 180 185 190Asp Ser Ser Asp Glu Glu Ile Cys Ala Lys Glu Ala Asn Pro Pro Thr 195 200 205Ala Ala Ala Phe Gln Pro Cys Ala Tyr Asn Gln Phe Gln Cys Leu Ser 210 215 220Arg Phe Thr Lys Val Tyr Thr Cys Leu Pro Glu Ser Leu Lys Cys Asp225 230 235 240Gly Asn Ile Asp Cys Leu Asp Leu Gly Asp Glu Ile Asp Cys Asp Val 245 250 255Pro Thr Cys Gly Gln Trp Leu Lys Tyr Phe Tyr Gly Thr Phe Asn Ser 260 265 270Pro Asn Tyr Pro Asp Phe Tyr Pro Pro Gly Ser Asn Cys Thr Trp Leu 275 280 285Ile Asp Thr Gly Asp His Arg Lys Val Ile Leu Arg Phe Thr Asp Phe 290 295 300Lys Leu Asp Gly Thr Gly Tyr Gly Asp Tyr Val Lys Ile Tyr Asp Gly305 310 315 320Leu Glu Glu Asn Pro His Lys Leu Leu Arg Val Leu Thr Ala Phe Asp 325 330 335Ser His Ala Pro Leu Thr Val Val Ser Ser

Ser Gly Gln Ile Arg Val 340 345 350His Phe Cys Ala Asp Lys Val Asn Ala Ala Arg Gly Phe Asn Ala Thr 355 360 365Tyr Gln Val Asp Gly Phe Cys Leu Pro Trp Glu Ile Pro Cys Gly Gly 370 375 380Asn Trp Gly Cys Tyr Thr Glu Gln Gln Arg Cys Asp Gly Tyr Trp His385 390 395 400Cys Pro Asn Gly Arg Asp Glu Thr Asn Cys Thr Met Cys Gln Lys Glu 405 410 415Glu Phe Pro Cys Ser Arg Asn Gly Val Cys Tyr Pro Arg Ser Asp Arg 420 425 430Cys Asn Tyr Gln Asn His Cys Pro Asn Gly Ser Asp Glu Lys Asn Cys 435 440 445Phe Phe Cys Gln Pro Gly Asn Phe His Cys Lys Asn Asn Arg Cys Val 450 455 460Phe Glu Ser Trp Val Cys Asp Ser Gln Asp Asp Cys Gly Asp Gly Ser465 470 475 480Asp Glu Glu Asn Cys Pro Val Ile Val Pro Thr Arg Val Ile Thr Ala 485 490 495Ala Val Ile Gly Ser Leu Ile Cys Gly Leu Leu Leu Val Ile Ala Leu 500 505 510Gly Cys Thr Cys Lys Leu Tyr Ser Leu Arg Met Phe Glu Arg Arg Ser 515 520 525Phe Glu Thr Gln Leu Ser Arg Val Glu Ala Glu Leu Leu Arg Arg Glu 530 535 540Ala Pro Pro Ser Tyr Gly Gln Leu Ile Ala Gln Gly Leu Ile Pro Pro545 550 555 560Val Glu Asp Phe Pro Val Cys Ser Pro Asn Gln Ala Ser Val Leu Glu 565 570 575Asn Leu Arg Leu Ala Val Arg Ser Gln Leu Gly Phe Thr Ser Val Arg 580 585 590Leu Pro Met Ala Gly Arg Ser Ser Asn Ile Trp Asn Arg Ile Phe Asn 595 600 605Phe Ala Arg Ser Arg His Ser Gly Ser Leu Ala Leu Val Ser Ala Asp 610 615 620Gly Asp Glu Val Val Pro Ser Gln Ser Thr Ser Arg Glu Pro Glu Arg625 630 635 640Asn His Thr His Arg Ser Leu Phe Ser Val Glu Ser Asp Asp Thr Asp 645 650 655Thr Glu Asn Glu Arg Arg Asp Met Ala Gly Ala Ser Gly Gly Val Ala 660 665 670Ala Pro Leu Pro Gln Lys Val Pro Pro Thr Thr Ala Val Glu Ala Thr 675 680 685Val Gly Ala Cys Ala Ser Ser Ser Thr Gln Ser Thr Arg Gly Gly His 690 695 700Ala Asp Asn Gly Arg Asp Val Thr Ser Val Glu Pro Pro Ser Val Ser705 710 715 720Pro Ala Arg His Gln Leu Thr Ser Ala Leu Ser Arg Met Thr Gln Gly 725 730 735Leu Arg Trp Val Arg Phe Thr Leu Gly Arg Ser Ser Ser Leu Ser Gln 740 745 750Asn Gln Ser Pro Leu Arg Gln Leu Asp Asn Gly Val Ser Gly Arg Glu 755 760 765Asp Asp Asp Asp Val Glu Met Leu Ile Pro Ile Ser Asp Gly Ser Ser 770 775 780Asp Phe Asp Val Asn Asp Cys Ser Arg Pro Leu Leu Asp Leu Ala Ser785 790 795 800Asp Gln Gly Gln Gly Leu Arg Gln Pro Tyr Asn Ala Thr Asn Pro Gly 805 810 815Val Arg Pro Ser Asn Arg Asp Gly Pro Cys Glu Arg Cys Gly Ile Val 820 825 830His Thr Ala Gln Ile Pro Asp Thr Cys Leu Glu Val Thr Leu Lys Asn 835 840 845Glu Thr Ser Asp Asp Glu Ala Leu Leu Leu Cys 850 855151070PRTHomo sapiens 15Met Val Leu Asp Asp Leu Pro Asn Leu Glu Asp Ile Tyr Thr Ser Leu1 5 10 15Cys Ser Ser Thr Met Glu Asp Ser Glu Met Asp Phe Asp Ser Gly Leu 20 25 30Glu Asp Asp Asp Thr Lys Ser Asp Ser Ile Leu Glu Asp Ser Thr Ile 35 40 45Phe Val Ala Phe Lys Gly Asn Ile Asp Asp Lys Asp Phe Lys Trp Lys 50 55 60Leu Asp Ala Ile Leu Lys Asn Val Pro Asn Leu Leu His Met Glu Ser65 70 75 80Ser Lys Leu Lys Val Gln Lys Val Glu Pro Trp Asn Ser Val Arg Val 85 90 95Thr Phe Asn Ile Pro Arg Glu Ala Ala Glu Arg Leu Arg Ile Leu Ala 100 105 110Gln Ser Asn Asn Gln Gln Leu Arg Asp Leu Gly Ile Leu Ser Val Gln 115 120 125Ile Glu Gly Glu Gly Ala Ile Asn Leu Ala Leu Ala Gln Asn Arg Ser 130 135 140Gln Asp Val Arg Met Asn Gly Pro Met Gly Ala Gly Asn Ser Val Arg145 150 155 160Met Glu Ala Gly Phe Pro Met Ala Ser Gly Pro Gly Ile Ile Arg Met 165 170 175Asn Asn Pro Ala Thr Val Met Ile Pro Pro Gly Gly Asn Val Ser Ser 180 185 190Ser Met Met Ala Pro Gly Pro Asn Pro Glu Leu Gln Pro Arg Thr Pro 195 200 205Arg Pro Ala Ser Gln Ser Asp Ala Met Asp Pro Leu Leu Ser Gly Leu 210 215 220His Ile Gln Gln Gln Ser His Pro Ser Gly Ser Leu Ala Pro Pro His225 230 235 240His Pro Met Gln Pro Val Ser Val Asn Arg Gln Met Asn Pro Ala Asn 245 250 255Phe Pro Gln Leu Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln 260 265 270Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Leu Gln Ala 275 280 285Arg Pro Pro Gln Gln His Gln Gln Gln Gln Pro Gln Gly Ile Arg Pro 290 295 300Gln Phe Thr Ala Pro Thr Gln Val Pro Val Pro Pro Gly Trp Asn Gln305 310 315 320Leu Pro Ser Gly Ala Leu Gln Pro Pro Pro Ala Gln Gly Ser Leu Gly 325 330 335Thr Met Thr Ala Asn Gln Gly Trp Lys Lys Ala Pro Leu Pro Gly Pro 340 345 350Met Gln Gln Gln Leu Gln Ala Arg Pro Ser Leu Ala Thr Val Gln Thr 355 360 365Pro Ser His Pro Pro Pro Pro Tyr Pro Phe Gly Ser Gln Gln Ala Ser 370 375 380Gln Ala His Thr Asn Phe Pro Gln Met Ser Asn Pro Gly Gln Phe Thr385 390 395 400Ala Pro Gln Met Lys Ser Leu Gln Gly Gly Pro Ser Arg Val Pro Thr 405 410 415Pro Leu Gln Gln Pro His Leu Thr Asn Lys Ser Pro Ala Ser Ser Pro 420 425 430Ser Ser Phe Gln Gln Gly Ser Pro Ala Ser Ser Pro Thr Val Asn Gln 435 440 445Thr Gln Gln Gln Met Gly Pro Arg Pro Pro Gln Asn Asn Pro Leu Pro 450 455 460Gln Gly Phe Gln Gln Pro Val Ser Ser Pro Gly Arg Asn Pro Met Val465 470 475 480Gln Gln Gly Asn Val Pro Pro Asn Phe Met Val Met Gln Gln Gln Pro 485 490 495Pro Asn Gln Gly Pro Gln Ser Leu His Pro Gly Leu Gly Gly Met Pro 500 505 510Lys Arg Leu Pro Pro Gly Phe Ser Ala Gly Gln Ala Asn Pro Asn Phe 515 520 525Met Gln Gly Gln Val Pro Ser Thr Thr Ala Thr Thr Pro Gly Asn Ser 530 535 540Gly Ala Pro Gln Leu Gln Ala Asn Gln Asn Val Gln His Ala Gly Gly545 550 555 560Gln Gly Ala Gly Pro Pro Gln Asn Gln Met Gln Val Ser His Gly Pro 565 570 575Pro Asn Met Met Gln Pro Ser Leu Met Gly Ile His Gly Asn Met Asn 580 585 590Asn Gln Gln Ala Gly Thr Ser Gly Val Pro Gln Val Asn Leu Ser Asn 595 600 605Met Gln Gly Gln Pro Gln Gln Gly Pro Pro Ser Gln Leu Met Gly Met 610 615 620His Gln Gln Ile Val Pro Ser Gln Gly Gln Met Val Gln Gln Gln Gly625 630 635 640Thr Leu Asn Pro Gln Asn Pro Met Ile Leu Ser Arg Ala Gln Leu Met 645 650 655Pro Gln Gly Gln Met Met Val Asn Pro Pro Ser Gln Asn Leu Gly Pro 660 665 670Ser Pro Gln Arg Met Thr Pro Pro Lys Gln Met Leu Ser Gln Gln Gly 675 680 685Pro Gln Met Met Ala Pro His Asn Gln Met Met Gly Pro Gln Gly Gln 690 695 700Val Leu Leu Gln Gln Asn Pro Met Ile Glu Gln Ile Met Thr Asn Gln705 710 715 720Met Gln Gly Asn Lys Gln Gln Phe Asn Thr Gln Asn Gln Ser Asn Val 725 730 735Met Pro Gly Pro Ala Gln Ile Met Arg Gly Pro Thr Pro Asn Met Gln 740 745 750Gly Asn Met Val Gln Phe Thr Gly Gln Met Ser Gly Gln Met Leu Pro 755 760 765Gln Gln Gly Pro Val Asn Asn Ser Pro Ser Gln Val Met Gly Ile Gln 770 775 780Gly Gln Val Leu Arg Pro Pro Gly Pro Ser Pro His Met Ala Gln Gln785 790 795 800His Gly Asp Pro Ala Thr Thr Ala Asn Asn Asp Val Ser Leu Ser Gln 805 810 815Met Met Pro Asp Val Ser Ile Gln Gln Thr Asn Met Val Pro Pro His 820 825 830Val Gln Ala Met Gln Gly Asn Ser Ala Ser Gly Asn His Phe Ser Gly 835 840 845His Gly Met Ser Phe Asn Ala Pro Phe Ser Gly Ala Pro Asn Gly Asn 850 855 860Gln Met Ser Cys Gly Gln Asn Pro Gly Phe Pro Val Asn Lys Asp Val865 870 875 880Thr Leu Thr Ser Pro Leu Leu Val Asn Leu Leu Gln Ser Asp Ile Ser 885 890 895Ala Gly His Phe Gly Val Asn Asn Lys Gln Asn Asn Thr Asn Ala Asn 900 905 910Lys Pro Lys Lys Lys Lys Pro Pro Arg Lys Lys Lys Asn Ser Gln Gln 915 920 925Asp Leu Asn Thr Pro Asp Thr Arg Pro Ala Gly Leu Glu Glu Ala Asp 930 935 940Gln Pro Pro Leu Pro Gly Glu Gln Gly Ile Asn Leu Asp Asn Ser Gly945 950 955 960Pro Lys Leu Pro Glu Phe Ser Asn Arg Pro Pro Ala Pro Ser Gln Asn 965 970 975Leu Val Ser Lys Glu Thr Ser Thr Thr Ala Leu Gln Ala Ser Val Ala 980 985 990Arg Pro Glu Leu Glu Val Asn Ala Ala Ile Val Ser Gly Gln Ser Ser 995 1000 1005Glu Pro Lys Glu Ile Val Glu Lys Ser Lys Ile Pro Gly Arg Arg 1010 1015 1020Asn Ser Arg Thr Glu Glu Pro Thr Val Ala Ser Glu Ser Val Glu 1025 1030 1035Asn Gly His Arg Lys Arg Ser Ser Arg Pro Ala Ser Ala Ser Ser 1040 1045 1050Ser Thr Lys Asp Ile Thr Ser Ala Val Gln Ser Lys Arg Arg Lys 1055 1060 1065Ser Lys 1070161630PRTHomo sapiens 16Met Pro Phe Ala Lys Arg Ile Val Glu Pro Gln Trp Leu Cys Arg Gln1 5 10 15Arg Arg Pro Ala Pro Gly Pro Ala Val Asp Ala Ser Gly Gly Ser Ala 20 25 30Glu Pro Pro Pro Pro Leu Gln Pro Pro Gly Arg Arg Asp Leu Asp Glu 35 40 45Val Glu Ala Pro Gly Pro Glu Glu Pro Ala Arg Ala Val Pro Ala Pro 50 55 60Ser Gly Leu Pro Pro Pro Pro Pro Pro Leu Pro Ala Pro Ala Asp Gln65 70 75 80Thr Gln Pro Pro His Gly Glu Ala Ser Val Ala Gly Glu Glu Ser Thr 85 90 95Ala Gly Ile Pro Glu Ala Ala Pro Ala Ala Gly Glu Ala Ser Ser Ala 100 105 110Ala Ala Ala Ala Ala Val Leu Leu Met Leu Asp Leu Cys Ala Val Ser 115 120 125Asn Ala Ala Leu Ala Arg Val Leu Arg Gln Leu Ser Asp Val Ala Arg 130 135 140His Ala Cys Ser Leu Phe Gln Glu Leu Glu Ser Asp Ile Gln Leu Thr145 150 155 160His Arg Arg Val Trp Ala Leu Gln Gly Lys Leu Gly Gly Val Gln Arg 165 170 175Val Leu Ser Thr Leu Asp Pro Lys Gln Glu Ala Val Pro Val Ser Asn 180 185 190Leu Asp Ile Glu Ser Lys Leu Ser Val Tyr Tyr Arg Ala Pro Trp His 195 200 205Gln Gln Arg Asn Ile Phe Leu Pro Ala Thr Arg Pro Pro Cys Val Glu 210 215 220Glu Leu His Arg His Ala Arg Gln Ser Leu Gln Ala Leu Arg Arg Glu225 230 235 240His Arg Ser Arg Ser Asp Arg Arg Glu Gln Arg Ala Ala Ala Pro Leu 245 250 255Ser Ile Ala Ala Pro Pro Leu Pro Ala Tyr Pro Pro Ala His Ser Gln 260 265 270Arg Arg Arg Glu Phe Lys Asp Arg His Phe Leu Thr Ser His Pro Pro 275 280 285Glu Asp Glu Asp Thr Asp Val Met Leu Gly Gln Arg Pro Lys Asn Pro 290 295 300Ile His Asn Ile Pro Ser Thr Leu Asp Lys Gln Thr Asn Trp Ser Lys305 310 315 320Ala Leu Pro Leu Pro Thr Pro Glu Glu Lys Met Lys Gln Asp Ala Gln 325 330 335Val Ile Ser Ser Cys Ile Ile Pro Ile Asn Val Thr Gly Val Gly Phe 340 345 350Asp Arg Glu Ala Ser Ile Arg Cys Ser Leu Val His Ser Gln Ser Val 355 360 365Leu Gln Arg Arg Arg Lys Leu Arg Arg Arg Lys Thr Ile Ser Gly Ile 370 375 380Pro Arg Arg Val Gln Gln Glu Ile Asp Ser Asp Glu Ser Pro Val Ala385 390 395 400Arg Glu Arg Asn Val Ile Val His Thr Asn Pro Asp Pro Ser Asn Thr 405 410 415Val Asn Arg Ile Ser Gly Thr Arg Asp Ser Glu Cys Gln Thr Glu Asp 420 425 430Ile Leu Ile Ala Ala Pro Ser Arg Arg Arg Ile Arg Ala Gln Arg Gly 435 440 445Gln Ser Ile Ala Ala Ser Leu Ser His Ser Ala Gly Asn Ile Ser Ala 450 455 460Leu Ala Asp Lys Gly Asp Thr Met Phe Thr Pro Ala Val Ser Ser Arg465 470 475 480Thr Arg Ser Arg Ser Leu Pro Arg Glu Gly Asn Arg Gly Gly Asp Ala 485 490 495Glu Pro Lys Val Gly Ala Lys Pro Ser Ala Tyr Glu Glu Gly Glu Ser 500 505 510Phe Val Gly Asp His Glu Arg Thr Pro Asn Asp Phe Ser Glu Ala Pro 515 520 525Ser Ser Pro Ser Ala Gln Asp His Gln Pro Thr Leu Gly Leu Ala Cys 530 535 540Ser Gln His Leu His Ser Pro Gln His Lys Leu Ser Glu Arg Gly Arg545 550 555 560Ser Arg Leu Ser Arg Met Ala Ala Asp Ser Gly Ser Cys Asp Ile Ser 565 570 575Ser Asn Ser Asp Thr Phe Gly Ser Pro Ile His Cys Ile Ser Thr Ala 580 585 590Gly Val Leu Leu Ser Ser His Met Asp Gln Lys Asp Asp His Gln Ser 595 600 605Ser Ser Gly Asn Trp Ser Gly Ser Ser Ser Thr Cys Pro Ser Gln Thr 610 615 620Ser Glu Thr Ile Pro Pro Ala Ala Ser Pro Pro Leu Thr Gly Ser Ser625 630 635 640His Cys Asp Ser Glu Leu Ser Leu Asn Thr Ala Pro His Ala Asn Glu 645 650 655Asp Ala Ser Val Phe Val Thr Glu Gln Tyr Asn Asp His Leu Asp Lys 660 665 670Val Arg Gly His Arg Ala Asn Ser Phe Thr Ser Thr Val Ala Asp Leu 675 680 685Leu Asp Asp Pro Asn Asn Ser Asn Thr Ser Asp Ser Glu Trp Asn Tyr 690 695 700Leu His His His His Asp Ala Ser Cys Arg Gln Asp Phe Ser Pro Glu705 710 715 720Arg Pro Lys Ala Asp Ser Leu Gly Cys Pro Ser Phe Thr Ser Met Ala 725 730 735Thr Tyr Asp Ser Phe Leu Glu Lys Ser Pro Ser Asp Lys Ala Asp Thr 740 745 750Ser Ser His Phe Ser Val Asp Thr Glu Gly Tyr Tyr Thr Ser Met His 755 760 765Phe Asp Cys Gly Leu Lys Gly Asn Lys Ser Tyr Val Cys His Tyr Ala 770 775 780Ala Leu Gly Pro Glu Asn Gly Gln Gly Val Gly Ala Ser Pro Gly Leu785 790 795 800Pro Asp Cys Ala Trp Gln Asp Tyr Leu Asp His Lys Arg Gln Gly Arg 805 810 815Pro Ser Ile Ser Phe Arg Lys Pro Lys Ala Lys Pro Thr Pro Pro Lys 820 825 830Arg Ser Ser Ser Leu Arg Lys Ser Asp Gly Asn Ala Asp Ile Ser Glu 835 840 845Lys Lys Glu Pro Lys Ile Ser Ser Gly Gln His Leu Pro His Ser Ser 850 855 860Arg Glu Met Lys Leu Pro Leu Asp Phe Ala Asn Thr Pro Ser Arg Met865 870 875

880Glu Asn Ala Asn Leu Pro Thr Lys Gln Glu Pro Ser Trp Ile Asn Gln 885 890 895Ser Glu Gln Gly Ile Lys Glu Pro Gln Leu Asp Ala Ser Asp Ile Pro 900 905 910Pro Phe Lys Asp Glu Val Ala Glu Ser Thr His Tyr Ala Asp Leu Trp 915 920 925Leu Leu Asn Asp Leu Lys Thr Asn Asp Pro Tyr Arg Ser Leu Ser Asn 930 935 940Ser Ser Thr Ala Thr Gly Thr Thr Val Ile Glu Cys Ile Lys Ser Pro945 950 955 960Glu Ser Ser Glu Ser Gln Thr Ser Gln Ser Glu Ser Arg Ala Thr Thr 965 970 975Pro Ser Leu Pro Ser Val Asp Asn Glu Phe Lys Leu Ala Ser Pro Glu 980 985 990Lys Leu Ala Gly Leu Ala Ser Pro Ser Ser Gly Tyr Ser Ser Gln Ser 995 1000 1005Glu Thr Pro Thr Ser Ser Phe Pro Thr Ala Phe Phe Ser Gly Pro 1010 1015 1020Leu Ser Pro Gly Gly Ser Lys Arg Lys Pro Lys Val Pro Glu Arg 1025 1030 1035Lys Ser Ser Leu Gln Gln Pro Ser Leu Lys Asp Gly Thr Ile Ser 1040 1045 1050Leu Ser Lys Asp Leu Glu Leu Pro Ile Ile Pro Pro Thr His Leu 1055 1060 1065Asp Leu Ser Ala Leu His Asn Val Leu Asn Lys Pro Phe His His 1070 1075 1080Arg His Pro Leu His Val Phe Thr His Asn Lys Gln Asn Thr Val 1085 1090 1095Gly Glu Thr Leu Arg Ser Asn Pro Pro Pro Ser Leu Ala Ile Thr 1100 1105 1110Pro Thr Ile Leu Lys Ser Val Asn Leu Arg Ser Ile Asn Lys Ser 1115 1120 1125Glu Glu Val Lys Gln Lys Glu Glu Asn Asn Thr Asp Leu Pro Tyr 1130 1135 1140Leu Glu Glu Ser Thr Leu Thr Thr Ala Ala Leu Ser Pro Ser Lys 1145 1150 1155Ile Arg Pro His Thr Ala Asn Lys Ser Val Ser Arg Gln Tyr Ser 1160 1165 1170Thr Glu Asp Thr Ile Leu Ser Phe Leu Asp Ser Ser Ala Val Glu 1175 1180 1185Met Gly Pro Asp Lys Leu His Leu Glu Lys Asn Ser Thr Phe Asp 1190 1195 1200Val Lys Asn Arg Cys Asp Pro Glu Thr Ile Thr Ser Ala Gly Ser 1205 1210 1215Ser Leu Leu Asp Ser Asn Val Thr Lys Asp Gln Val Arg Thr Glu 1220 1225 1230Thr Glu Pro Ile Pro Glu Asn Thr Pro Thr Lys Asn Cys Ala Phe 1235 1240 1245Pro Thr Glu Gly Phe Gln Arg Val Ser Ala Ala Arg Pro Asn Asp 1250 1255 1260Leu Asp Gly Lys Ile Ile Gln Tyr Gly Pro Gly Pro Asp Glu Thr 1265 1270 1275Leu Glu Gln Val Gln Lys Ala Pro Ser Ala Gly Leu Glu Glu Val 1280 1285 1290Ala Gln Pro Glu Ser Val Asp Val Ile Thr Ser Gln Ser Asp Ser 1295 1300 1305Pro Thr Arg Ala Thr Asp Val Ser Asn Gln Phe Lys His Gln Phe 1310 1315 1320Val Met Ser Arg His His Asp Lys Val Pro Gly Thr Ile Ser Tyr 1325 1330 1335Glu Ser Glu Ile Thr Ser Val Asn Ser Phe Pro Glu Lys Cys Ser 1340 1345 1350Lys Gln Glu Asn Ile Ala Ser Gly Ile Ser Ala Lys Ser Ala Ser 1355 1360 1365Asp Asn Ser Lys Ala Glu Glu Thr Gln Gly Asn Val Asp Glu Ala 1370 1375 1380Ser Leu Lys Glu Ser Ser Pro Ser Asp Asp Ser Ile Ile Ser Pro 1385 1390 1395Leu Ser Glu Asp Ser Gln Ala Glu Ala Glu Gly Val Phe Val Ser 1400 1405 1410Pro Asn Lys Pro Arg Thr Thr Glu Asp Leu Phe Ala Val Ile His 1415 1420 1425Arg Ser Lys Arg Lys Val Leu Gly Arg Lys Asp Ser Gly Asp Met 1430 1435 1440Ser Val Arg Ser Lys Ser Arg Ala Pro Leu Ser Ser Ser Ser Ser 1445 1450 1455Ser Ala Ser Ser Ile Thr Ser Pro Ser Ser Asn Val Thr Thr Pro 1460 1465 1470Asn Ser Gln Arg Ser Pro Gly Leu Ile Tyr Arg Asn Ala Lys Lys 1475 1480 1485Ser Asn Thr Ser Asn Glu Glu Phe Lys Leu Leu Leu Leu Lys Lys 1490 1495 1500Gly Ser Arg Ser Asp Ser Ser Tyr Arg Met Ser Ala Thr Glu Ile 1505 1510 1515Leu Lys Ser Pro Ile Leu Pro Lys Pro Pro Gly Glu Leu Thr Ala 1520 1525 1530Glu Ser Pro Gln Ser Thr Asp Asp Ala His Gln Gly Ser Gln Gly 1535 1540 1545Ala Glu Ala Leu Ser Pro Leu Ser Pro Cys Ser Pro Arg Val Asn 1550 1555 1560Ala Glu Gly Phe Ser Ser Lys Ser Phe Ala Thr Ser Ala Ser Ala 1565 1570 1575Arg Val Gly Arg Ser Arg Ala Pro Pro Ala Ala Ser Ser Ser Arg 1580 1585 1590Tyr Ser Val Arg Cys Arg Leu Tyr Asn Thr Pro Met Gln Ala Ile 1595 1600 1605Ser Glu Gly Glu Thr Glu Asn Ser Asp Gly Ser Pro His Asp Asp 1610 1615 1620Arg Ser Ser Gln Ser Ser Thr 1625 1630171388PRTHomo sapiens 17Met Ser Ile Pro Leu His Ser Leu Arg Phe Asn Asn Thr Met Arg Glu1 5 10 15Glu Asn Val Glu Pro Gln Asn Lys Gln Met Ala Phe Cys Arg Pro Met 20 25 30Thr Glu Thr Arg Ala Asp Val Gln Ile Leu His Ser His Val Gln Leu 35 40 45Pro Ile Val Ser Thr Ser Ala Ser Asp Pro Gly Gly Thr Ser Thr Gln 50 55 60Leu Met Thr Ser Pro Val Phe Asp Thr Met Ser Ala Pro Leu Met Gly65 70 75 80Val Pro Asn Ser Gly Ala Leu Ser Pro Pro Leu Met Pro Ala Ser Asp 85 90 95Ser Gly Ala Leu Ser Pro Leu Leu Met Pro Ala Ser Asp Ser Gly Ala 100 105 110Leu Ser Pro Leu Leu Met Pro Ala Leu Asp Ser Gly Thr Leu Ser Pro 115 120 125Leu Leu Ser Thr Ser Glu Tyr Gly Val Met Ser Pro Gly Met Met Thr 130 135 140Ile Pro Asp Phe Gly Thr Met Ser Ala Thr Leu Met Val Ala Pro Asp145 150 155 160Ser Ala Glu Ile Ser Pro Leu Ala Met Pro Ala Pro Ser Ser Gly Val 165 170 175Val Cys Thr Pro Ile Met Ser Thr Ser Ser Ser Glu Ala Met Ser Thr 180 185 190Pro Leu Met Leu Ala Pro Asp Ser Gly Glu Leu Ser Pro Ile Leu Met 195 200 205Gln Asp Met Asn Pro Gly Val Met Ser Thr Gln Pro Val Pro Ala Pro 210 215 220Ser Ser Glu Ala Met Ser Pro Leu Gln Ile Thr Asp Glu Asp Thr Glu225 230 235 240Ala Met Ser Lys Val Leu Met Thr Ala Leu Ala Ser Gly Glu Ile Ser 245 250 255Ser Leu Leu Met Ser Gly Thr Asp Ser Glu Ala Ile Ser Ser Leu Ile 260 265 270Met Ser Ala Val Ala Ser Gly Gly Thr Ser Pro Gln Pro Thr Ser Thr 275 280 285Gln Asn Ser Gly Gly Ile Pro Thr Pro Leu Met Ser Asp Leu Asp Ser 290 295 300Gly Ile Met Ser Ser Leu Leu Met Ser Ser Pro Gly Ser Glu Val Met305 310 315 320Ser Thr Pro Leu Leu Ser Val Pro Asp Ala Gly Glu Met Ser Thr Leu 325 330 335Pro Lys Pro Ala Pro Asp Ala Glu Ala Met Ser Pro Ala Leu Met Thr 340 345 350Ala Leu Pro Ser Gly Val Met Pro Thr Gln Thr Met Pro Ala Pro Gly 355 360 365Ser Gly Ala Met Ser Pro Trp Ser Thr Gln Asn Val Asp Ser Glu Met 370 375 380Met Ser Asn Pro Pro Val Arg Ala Thr Ala Ser Gly Val Met Ser Ala385 390 395 400Pro Pro Val Arg Ala Leu Asp Ser Gly Ala Met Ser Thr Pro Leu Met 405 410 415Gly Ala Pro Ala Ser Gly Asn Met Ser Thr Leu Gln Lys Thr Val Pro 420 425 430Ala Ser Gly Ala Met Thr Thr Ser Leu Met Thr Val Pro Ser Ser Gly 435 440 445Val Met Ser Thr Glu Gln Met Ser Ala Thr Ala Ser Arg Val Met Ser 450 455 460Ala Gln Leu Thr Met Ala Lys Thr Ser Gly Ala Met Pro Thr Gly Ser465 470 475 480Met Lys Ala Val Ala Lys Gln Tyr Lys Arg Ala Thr Ala Ser Gly Lys 485 490 495Met Ser Thr Pro Leu Arg Arg Ala Pro Thr Ser Gly Ala Met Ser Thr 500 505 510Gln Pro Val Thr Ala Thr Ala Ser Glu Thr Met Ser Met Pro Gln Leu 515 520 525Thr Val Pro Ala Ser Gly Ser Met Ser Met Leu Gln Met Arg Ala Pro 530 535 540Val Ser Glu Ala Met Ser Met Pro Gln Met Arg Thr Met Ala Ser Gly545 550 555 560Leu Thr Ser Ala Ala Gln Met Lys Ala Met Thr Ser Gly Ala Met Ser 565 570 575Thr Pro Leu Met Thr Ala Gln Thr Ser Gly Ser Thr Ser Thr Leu Leu 580 585 590Met Arg Asp Thr Ala Ser Gly Val Met Ser Cys Pro Gln Met Arg Ser 595 600 605Leu Ala Ser Gly Ala Leu Ser Lys Pro Leu Met Thr Pro Lys Ala Ser 610 615 620Gly Thr Met Phe Thr Glu Lys Met Thr Thr Thr Ala Ser Glu Ala Met625 630 635 640Pro Thr Leu Leu Met Arg Asp Thr Val Ser Gly Ala Leu Ser Met Pro 645 650 655Gln Met Thr Asp Thr Ala Ser Gly Gly Leu Ser Ala Ser Leu Met Arg 660 665 670Asp Thr Ala Ser Gly Ala Met Ser Thr Ser Gln Met Thr Ala Thr Val 675 680 685Ser Gly Gly Met Ser Met Pro Leu Met Arg Ala Gln Asp Pro Gly Val 690 695 700Met Pro Ala Ser Leu Met Arg Ala Lys Val Ser Gly Lys Met Leu Ser705 710 715 720Gln Pro Met Ser Thr Gln Asp Pro Gly Gly Met Ser Met Ser Pro Met 725 730 735Lys Ser Met Thr Ala Gly Gly Met Gln Met Asn Ser Pro Thr Ser Asp 740 745 750Val Met Ser Thr Pro Thr Val Arg Ala Trp Thr Ser Glu Thr Met Ser 755 760 765Thr Pro Leu Met Arg Thr Ser Asp Pro Gly Glu Arg Pro Ser Leu Leu 770 775 780Thr Arg Ala Ser Ser Ser Gly Glu Met Ser Leu Pro Leu Met Arg Ala785 790 795 800Pro Ala Ser Gly Glu Ile Ala Thr Pro Leu Arg Ser Pro Ala Tyr Gly 805 810 815Ala Met Ser Ala Pro Gln Met Thr Ala Thr Ala Ser Gly Met Met Ser 820 825 830Ser Met Pro Gln Val Lys Ala Pro Ile Ser Gly Ala Met Ser Met Pro 835 840 845Leu Thr Arg Ser Thr Ala Ser Gly Gly Met Ser Met Pro Leu Met Arg 850 855 860Ala Pro Asp Ser Arg Val Thr Ser Thr Ser Gln Met Met Pro Thr Ala865 870 875 880Ser Gly Asp Met Cys Thr Leu Pro Val Arg Ala Pro Ala Ser Gly Gly 885 890 895Val Ser Ser Pro Leu Val Arg Ala Pro Ala Ser Gly Thr Met Ser Thr 900 905 910Pro Leu Arg Arg Pro Ser Ala Cys Glu Thr Val Ser Thr Glu Leu Met 915 920 925Arg Ala Ser Ala Ser Gly His Met Ser Thr Ala Gln Thr Thr Ala Met 930 935 940Val Ser Gly Gly Met Ser Lys Pro Leu Met Arg Ala Pro Ala Ser Gly945 950 955 960Thr Met Pro Met Pro Leu Met Ser Ala Met Ala Ser Gly Glu Met Ser 965 970 975Met Pro Leu Met Glu Thr Met Ala Ser Gly Ala Thr Ser Thr Leu Gln 980 985 990Thr Ser Val Ala Asn Ser Arg Ser Met Ser Leu Ser Gln Thr Thr Tyr 995 1000 1005Thr Val Ser Gly Arg Met Ala Thr Ala Pro Ile Arg Ala Ser Ala 1010 1015 1020Ser Gly Ala Arg Ser Thr Ser Phe Met Arg Ala Ser Val Ser Gly 1025 1030 1035Ser Met Pro Met Pro Leu Pro Arg Ala Thr Ala Ser Gly Cys Gly 1040 1045 1050Met Gly Met Ser Met Pro Gln Met Thr Ala Thr Asp Ser Arg Gly 1055 1060 1065Met Ser Thr Pro Leu Met Arg Ala Ser Gly Pro Gly Thr Met Ser 1070 1075 1080Thr Pro Gln Thr Ala Phe Gly Val Met Ser Thr Pro Glu Ile Lys 1085 1090 1095Ala Thr Asp Ser Gly Glu Ala Ser Thr Ser His Ile Asn Ile Thr 1100 1105 1110Ala Ser Gly Ser Lys Pro Thr Ser His Met Thr Ala Thr Thr Pro 1115 1120 1125Glu Thr Ala Lys Pro Pro Pro Lys Glu Val Pro Ser Phe Gly Met 1130 1135 1140Leu Thr Pro Ala Leu Cys Tyr Leu Leu Glu Glu Gln Glu Ala Ala 1145 1150 1155Arg Gly Ser Cys Ser Val Glu Glu Glu Met Glu Ile Asp Glu Glu 1160 1165 1170Lys Gln Met Lys Gly Phe Leu Asp Asp Ser Glu Arg Met Ala Phe 1175 1180 1185Leu Val Ser Leu His Leu Gly Ala Ala Glu Arg Trp Phe Ile Leu 1190 1195 1200Gln Met Glu Val Gly Glu Pro Leu Ser His Glu Asn Lys Ser Phe 1205 1210 1215Leu Arg Arg Ser Gln Gly Ile Tyr Asp Ser Leu Ser Glu Ile Asp 1220 1225 1230Ile Leu Ser Ala Val Leu Cys His Pro Lys Gln Gly Gln Lys Ser 1235 1240 1245Val Arg Gln Tyr Ala Thr Asp Phe Leu Leu Leu Ala Arg His Leu 1250 1255 1260Ser Trp Ser Asp Ala Ile Leu Arg Thr Arg Phe Leu Glu Gly Leu 1265 1270 1275Ser Glu Ala Val Thr Thr Lys Met Gly Arg Ile Phe Leu Lys Val 1280 1285 1290Ala Gly Ser Leu Lys Glu Leu Ile Asp Arg Ser Leu Tyr Thr Glu 1295 1300 1305Cys Gln Leu Ala Glu Glu Lys Asp Ser Pro Gly Asn Ser Ser Gln 1310 1315 1320Val Leu Pro Thr Ala Cys Lys Arg Asn Asn Glu Glu Ala Met Gly 1325 1330 1335Asn Glu Leu Ser Ser Gln Gln Gln Thr Glu Glu His Gln His Val 1340 1345 1350Ser Lys Arg Cys Tyr Tyr Leu Lys Glu His Gly Asp Pro Gln Glu 1355 1360 1365Gly Leu His Asp His Leu Gly Gln Ser Thr Gly His His Gln Lys 1370 1375 1380Ala His Thr Asn Lys 1385181312PRTHomo sapiens 18Met Glu Glu Glu Asp Glu Ser Arg Gly Lys Thr Glu Glu Ser Gly Glu1 5 10 15Asp Arg Gly Asp Gly Pro Pro Asp Arg Asp Pro Thr Leu Ser Pro Ser 20 25 30Ala Phe Ile Leu Arg Ala Ile Gln Gln Ala Val Gly Ser Ser Leu Gln 35 40 45Gly Asp Leu Pro Asn Asp Lys Asp Gly Ser Arg Cys His Gly Leu Arg 50 55 60Trp Arg Arg Cys Arg Ser Pro Arg Ser Glu Pro Arg Ser Gln Glu Ser65 70 75 80Gly Gly Thr Asp Thr Ala Thr Val Leu Asp Met Ala Thr Asp Ser Phe 85 90 95Leu Ala Gly Leu Val Ser Val Leu Asp Pro Pro Asp Thr Trp Val Pro 100 105 110Ser Arg Leu Asp Leu Arg Pro Gly Glu Ser Glu Asp Met Leu Glu Leu 115 120 125Val Ala Glu Val Arg Ile Gly Asp Arg Asp Pro Ile Pro Leu Pro Val 130 135 140Pro Ser Leu Leu Pro Arg Leu Arg Ala Trp Arg Thr Gly Lys Thr Val145 150 155 160Ser Pro Gln Ser Asn Ser Ser Arg Pro Thr Cys Ala Arg His Leu Thr 165 170 175Leu Gly Thr Gly Asp Gly Gly Pro Ala Pro Pro Pro Ala Pro Ser Ser 180 185 190Ala Ser Ser Ser Pro Ser Pro Ser Pro Ser Ser Ser Ser Pro Ser Pro 195 200 205Pro Pro Pro Pro Pro Pro Pro Ala Pro Pro Ala Pro Pro Ala Pro Arg 210 215 220Phe Asp Ile Tyr Asp Pro Phe His Pro Thr Asp Glu Ala Tyr Ser Pro225 230 235 240Pro Pro Ala Pro Glu Gln Lys Tyr Asp Pro Phe Glu Pro Thr Gly Ser 245 250 255Asn Pro Ser Ser Ser Ala Gly Thr Pro Ser Pro Glu Glu Glu Glu Glu 260 265 270Glu Glu Glu Glu Glu Glu Glu Glu Glu Glu Asp Glu Glu Glu Glu Glu 275 280 285Gly Leu Ser Gln Ser Ile Ser Arg Ile Ser Glu Thr Leu Ala Gly Ile 290 295 300Tyr Asp Asp Asn Ser Leu Ser Gln Asp Phe Pro Gly Asp Glu Ser Pro305

310 315 320Arg Pro Asp Ala Gln Pro Thr Gln Pro Thr Pro Ala Pro Gly Thr Pro 325 330 335Pro Gln Val Asp Ser Thr Arg Ala Asp Gly Ala Met Arg Arg Arg Val 340 345 350Phe Val Val Gly Thr Glu Ala Glu Ala Cys Arg Glu Gly Lys Val Ser 355 360 365Val Glu Val Val Thr Ala Gly Gly Ala Ala Leu Pro Pro Pro Leu Leu 370 375 380Pro Pro Gly Asp Ser Glu Ile Glu Glu Gly Glu Ile Val Gln Pro Glu385 390 395 400Glu Glu Pro Arg Leu Ala Leu Ser Leu Phe Arg Pro Gly Gly Arg Ala 405 410 415Ala Arg Pro Thr Pro Ala Ala Ser Ala Thr Pro Thr Ala Gln Pro Leu 420 425 430Pro Gln Pro Pro Ala Pro Arg Ala Pro Glu Gly Asp Asp Phe Leu Ser 435 440 445Leu His Ala Glu Ser Asp Gly Glu Gly Ala Leu Gln Val Asp Leu Gly 450 455 460Glu Pro Ala Pro Ala Pro Pro Ala Ala Asp Ser Arg Trp Gly Gly Leu465 470 475 480Asp Leu Arg Arg Lys Ile Leu Thr Gln Arg Arg Glu Arg Tyr Arg Gln 485 490 495Arg Ser Pro Ser Pro Ala Pro Ala Pro Ala Pro Ala Ala Ala Ala Gly 500 505 510Pro Pro Thr Arg Lys Lys Ser Arg Arg Glu Arg Lys Arg Ser Gly Glu 515 520 525Ala Lys Glu Ala Ala Ser Ser Ser Ser Gly Thr Gln Pro Ala Pro Pro 530 535 540Ala Pro Ala Ser Pro Trp Asp Ser Lys Lys His Arg Ser Arg Asp Arg545 550 555 560Lys Pro Gly Ser His Ala Ser Ser Ser Ala Arg Arg Arg Ser Arg Ser 565 570 575Arg Ser Arg Ser Arg Ser Thr Arg Arg Arg Ser Arg Ser Thr Asp Arg 580 585 590Arg Arg Gly Gly Ser Arg Arg Ser Arg Ser Arg Glu Lys Arg Arg Arg 595 600 605Arg Arg Arg Ser Ala Ser Pro Pro Pro Ala Thr Ser Ser Ser Ser Ser 610 615 620Ser Arg Arg Glu Arg His Arg Gly Lys His Arg Asp Gly Gly Gly Ser625 630 635 640Lys Lys Lys Lys Lys Arg Ser Arg Ser Arg Gly Glu Lys Arg Ser Gly 645 650 655Asp Gly Ser Glu Lys Ala Pro Ala Pro Ala Pro Pro Pro Ser Gly Ser 660 665 670Thr Ser Cys Gly Asp Arg Asp Ser Arg Arg Arg Gly Ala Val Pro Pro 675 680 685Ser Ile Gln Asp Leu Thr Asp His Asp Leu Phe Ala Ile Lys Arg Thr 690 695 700Ile Thr Val Gly Arg Leu Asp Lys Ser Asp Pro Arg Gly Pro Ser Pro705 710 715 720Ala Pro Ala Ser Ser Pro Lys Arg Glu Val Leu Tyr Asp Ser Glu Gly 725 730 735Leu Ser Gly Glu Glu Arg Gly Gly Lys Ser Ser Gln Lys Asp Arg Arg 740 745 750Arg Ser Gly Ala Ala Ser Ser Ser Ser Ser Ser Arg Glu Lys Gly Ser 755 760 765Arg Arg Lys Ala Leu Asp Gly Gly Asp Arg Asp Arg Asp Arg Asp Arg 770 775 780Asp Arg Asp Arg Asp Arg Ser Ser Lys Lys Ala Arg Pro Pro Lys Glu785 790 795 800Ser Ala Pro Ser Ser Gly Pro Pro Pro Lys Pro Pro Val Ser Ser Gly 805 810 815Ser Gly Ser Ser Ser Ser Ser Ser Ser Cys Ser Ser Arg Lys Val Lys 820 825 830Leu Gln Ser Lys Val Ala Val Leu Ile Arg Glu Gly Val Ser Ser Thr 835 840 845Thr Pro Ala Lys Asp Ala Ala Ser Ala Gly Leu Gly Ser Ile Gly Val 850 855 860Lys Phe Ser Arg Asp Arg Glu Ser Arg Ser Pro Phe Leu Lys Pro Asp865 870 875 880Glu Arg Ala Pro Thr Glu Met Ala Lys Ala Ala Pro Gly Ser Thr Lys 885 890 895Pro Lys Lys Thr Lys Val Lys Ala Lys Ala Gly Ala Lys Lys Thr Lys 900 905 910Gly Thr Lys Gly Lys Thr Lys Pro Ser Lys Thr Arg Lys Lys Val Arg 915 920 925Ser Gly Gly Gly Ser Gly Gly Ser Gly Gly Gln Val Ser Leu Lys Lys 930 935 940Ser Lys Ala Asp Ser Cys Ser Gln Ala Ala Gly Thr Lys Gly Ala Glu945 950 955 960Glu Thr Ser Trp Ser Gly Glu Glu Arg Ala Ala Lys Val Pro Ser Thr 965 970 975Pro Pro Pro Lys Ala Ala Pro Pro Pro Pro Ala Leu Thr Pro Asp Ser 980 985 990Gln Thr Val Asp Ser Ser Cys Lys Thr Pro Glu Val Ser Phe Leu Pro 995 1000 1005Glu Glu Ala Thr Glu Glu Ala Gly Val Arg Gly Gly Ala Glu Glu 1010 1015 1020Glu Glu Glu Glu Glu Glu Glu Glu Glu Glu Glu Glu Glu Glu Glu 1025 1030 1035Glu Gln Gln Pro Ala Thr Thr Thr Ala Thr Ser Thr Ala Ala Ala 1040 1045 1050Ala Pro Ser Thr Ala Pro Ser Ala Gly Ser Thr Ala Gly Asp Ser 1055 1060 1065Gly Ala Glu Asp Gly Pro Ala Ser Arg Val Ser Gln Leu Pro Thr 1070 1075 1080Leu Pro Pro Pro Met Pro Trp Asn Leu Pro Ala Gly Val Asp Cys 1085 1090 1095Thr Thr Ser Gly Val Leu Ala Leu Thr Ala Leu Leu Phe Lys Met 1100 1105 1110Glu Glu Ala Asn Leu Ala Ser Arg Ala Lys Ala Gln Glu Leu Ile 1115 1120 1125Gln Ala Thr Asn Gln Ile Leu Ser His Arg Lys Pro Pro Ser Ser 1130 1135 1140Leu Gly Met Thr Pro Ala Pro Val Pro Thr Ser Leu Gly Leu Pro 1145 1150 1155Pro Gly Pro Ser Ser Tyr Leu Leu Pro Gly Ser Leu Pro Leu Gly 1160 1165 1170Gly Cys Gly Ser Thr Pro Pro Thr Pro Thr Gly Leu Ala Ala Thr 1175 1180 1185Ser Asp Lys Arg Glu Gly Ser Ser Ser Ser Glu Gly Arg Gly Asp 1190 1195 1200Thr Asp Lys Tyr Leu Lys Lys Leu His Thr Gln Glu Arg Ala Val 1205 1210 1215Glu Glu Val Lys Leu Ala Ile Lys Pro Tyr Tyr Gln Lys Lys Asp 1220 1225 1230Ile Thr Lys Glu Glu Tyr Lys Asp Ile Leu Arg Lys Ala Val His 1235 1240 1245Lys Ile Cys His Ser Lys Ser Gly Glu Ile Asn Pro Val Lys Val 1250 1255 1260Ser Asn Leu Val Arg Ala Tyr Val Gln Arg Tyr Arg Tyr Phe Arg 1265 1270 1275Lys His Gly Arg Lys Pro Gly Asp Pro Pro Gly Pro Pro Arg Pro 1280 1285 1290Pro Lys Glu Pro Gly Pro Pro Asp Lys Gly Gly Pro Gly Leu Pro 1295 1300 1305Leu Pro Pro Leu 1310191336PRTHomo sapiens 19Met Glu Asn Leu Pro Ala Val Thr Thr Glu Glu Pro Thr Pro Met Gly1 5 10 15Arg Gly Pro Val Gly Pro Ser Gly Gly Gly Ser Thr Arg Asp Gln Val 20 25 30Arg Thr Val Val Met Arg Pro Ser Val Ser Trp Glu Lys Ala Gly Pro 35 40 45Glu Glu Ala Lys Ala Pro Val Arg Gly Asp Glu Ala Pro Pro Ala Arg 50 55 60Val Ala Gly Pro Ala Ala Gly Thr Pro Pro Cys Gln Met Gly Val Tyr65 70 75 80Pro Thr Asp Leu Thr Leu Gln Leu Leu Ala Val Arg Arg Lys Ser Arg 85 90 95Leu Arg Asp Pro Gly Leu Gln Gln Thr Leu Arg Gly Gln Leu Arg Leu 100 105 110Leu Glu Asn Asp Ser Arg Glu Met Ala Arg Val Leu Gly Glu Leu Ser 115 120 125Ala Arg Leu Leu Ser Ile His Ser Asp Gln Asp Arg Ile Val Val Thr 130 135 140Phe Lys Thr Phe Glu Glu Ile Trp Lys Phe Ser Thr Tyr His Ala Leu145 150 155 160Gly Phe Thr His His Cys Leu Ala Asn Leu Leu Met Asp Gln Ala Phe 165 170 175Trp Leu Leu Leu Pro Ser Glu Glu Glu Glu Thr Ala Ile Gln Val His 180 185 190Val Asp Glu Asn Ala Leu Arg Leu Thr His Glu Ser Leu Leu Ile Gln 195 200 205Glu Gly Pro Phe Phe Val Leu Cys Pro Asp His His Val Arg Val Met 210 215 220Thr Gly Pro Arg Asp Ala Gly Asn Gly Pro Gln Ala Leu Arg Gln Ala225 230 235 240Ser Gly Ala Pro Gln Gly Glu Ala Ala Pro Glu Thr Asp Ser Ser Pro 245 250 255Pro Ser Pro Ser Val Ser Ser Glu Glu Val Ala Val Ala Ala Ala Pro 260 265 270Glu Pro Leu Ile Pro Phe His Gln Trp Ala Leu Arg Ile Pro Gln Asp 275 280 285Pro Ile Asp Asp Ala Met Gly Gly Pro Val Met Pro Gly Asn Pro Leu 290 295 300Met Ala Val Gly Leu Ala Ser Ala Leu Ala Asp Phe Gln Gly Ser Gly305 310 315 320Pro Glu Glu Met Thr Phe Arg Gly Gly Asp Leu Ile Glu Ile Leu Gly 325 330 335Ala Gln Val Pro Ser Leu Pro Trp Cys Val Gly Arg His Ala Ala Ser 340 345 350Gly Arg Val Gly Phe Val Arg Ser Ser Leu Ile Ser Met Gln Gly Pro 355 360 365Val Ser Glu Leu Glu Ser Ala Ile Phe Leu Asn Glu Glu Glu Lys Ser 370 375 380Phe Phe Ser Glu Gly Cys Phe Ser Glu Glu Asp Ala Arg Gln Leu Leu385 390 395 400Arg Arg Met Ser Gly Thr Asp Val Cys Ser Val Tyr Ser Leu Asp Ser 405 410 415Val Glu Glu Ala Glu Thr Glu Gln Pro Gln Glu Lys Glu Ile Pro Pro 420 425 430Pro Cys Leu Ser Pro Glu Pro Gln Glu Thr Leu Gln Lys Val Lys Asn 435 440 445Val Leu Glu Gln Cys Lys Thr Cys Pro Gly Cys Pro Gln Glu Pro Ala 450 455 460Ser Trp Gly Leu Cys Ala Ala Ser Ser Asp Val Ser Leu Gln Asp Pro465 470 475 480Glu Glu Pro Ser Phe Cys Leu Glu Ala Glu Asp Asp Trp Glu Asp Pro 485 490 495Glu Ala Leu Ser Ser Leu Leu Leu Phe Leu Asn Ala Pro Gly Tyr Lys 500 505 510Ala Ser Phe Arg Gly Leu Tyr Asp Val Ala Leu Pro Trp Leu Ser Ser 515 520 525Val Phe Arg Ser Phe Ser Asp Glu Glu Glu Leu Thr Gly Arg Leu Ala 530 535 540Gln Ala Arg Gly Ala Ala Lys Lys Ala Gly Leu Leu Met Ala Leu Ala545 550 555 560Arg Leu Cys Phe Leu Leu Gly Arg Leu Cys Ser Arg Arg Leu Lys Leu 565 570 575Ser Gln Ala Arg Val Tyr Phe Glu Glu Ala Leu Gly Ala Leu Glu Gly 580 585 590Ser Phe Gly Asp Leu Phe Leu Val Val Ala Val Tyr Ala Asn Leu Ala 595 600 605Ser Ile Tyr Arg Lys Gln Lys Asn Arg Glu Lys Cys Ala Gln Val Val 610 615 620Pro Lys Ala Met Ala Leu Leu Leu Gly Thr Pro Asp His Ile Cys Ser625 630 635 640Thr Glu Ala Glu Gly Glu Leu Leu Gln Leu Ala Leu Arg Arg Ala Val 645 650 655Gly Gly Gln Ser Leu Gln Ala Glu Ala Arg Ala Cys Phe Leu Leu Ala 660 665 670Arg His His Val His Leu Lys Gln Pro Glu Glu Ala Leu Pro Phe Leu 675 680 685Glu Arg Leu Leu Leu Leu His Arg Asp Ser Gly Ala Pro Glu Ala Ala 690 695 700Trp Leu Ser Asp Cys Tyr Leu Leu Leu Ala Asp Ile Tyr Ser Arg Lys705 710 715 720Cys Leu Pro His Leu Val Leu Ser Cys Val Lys Val Ala Ser Leu Arg 725 730 735Thr Arg Gly Ser Leu Ala Gly Ser Leu Arg Ser Val Asn Leu Val Leu 740 745 750Gln Asn Ala Pro Gln Pro His Ser Leu Pro Ala Gln Thr Ser His Tyr 755 760 765Leu Arg Gln Ala Leu Ala Ser Leu Thr Pro Gly Thr Gly Gln Ala Leu 770 775 780Arg Gly Pro Leu Tyr Thr Ser Leu Ala Gln Leu Tyr Ser His His Gly785 790 795 800Cys His Gly Pro Ala Ile Thr Phe Met Thr Gln Ala Val Glu Ala Ser 805 810 815Ala Ile Ala Gly Val Arg Ala Ile Val Asp His Leu Val Ala Leu Ala 820 825 830Trp Leu His Val Leu His Gly Gln Ser Pro Val Ala Leu Asp Ile Leu 835 840 845Gln Ser Val Arg Asp Ala Val Val Ala Ser Glu Asp Gln Glu Gly Val 850 855 860Ile Ala Asn Met Val Ala Val Ala Leu Lys Arg Thr Gly Arg Thr Arg865 870 875 880Gln Ala Ala Glu Ser Tyr Tyr Arg Ala Leu Arg Val Ala Arg Asp Leu 885 890 895Gly Gln Gln Arg Asn Gln Ala Val Gly Leu Ala Asn Phe Gly Ala Leu 900 905 910Cys Leu His Ala Gly Ala Ser Arg Leu Ala Gln His Tyr Leu Leu Glu 915 920 925Ala Val Arg Leu Phe Ser Arg Leu Pro Leu Gly Glu Cys Gly Arg Asp 930 935 940Phe Thr His Val Leu Leu Gln Leu Gly His Leu Cys Thr Arg Gln Gly945 950 955 960Pro Ala Gln Gln Gly Lys Gly Tyr Tyr Glu Trp Ala Leu Leu Val Ala 965 970 975Val Glu Met Gly His Val Glu Ser Gln Leu Arg Ala Val Gln Arg Leu 980 985 990Cys His Phe Tyr Ser Ala Val Met Pro Ser Glu Ala Gln Cys Val Ile 995 1000 1005Tyr His Glu Leu Gln Leu Ser Leu Ala Cys Lys Val Ala Asp Lys 1010 1015 1020Val Leu Glu Gly Gln Leu Leu Glu Thr Ile Ser Gln Leu Tyr Leu 1025 1030 1035Ser Leu Gly Thr Glu Arg Ala Tyr Lys Ser Ala Leu Asp Tyr Thr 1040 1045 1050Lys Arg Ser Leu Gly Ile Phe Ile Asp Leu Gln Lys Lys Glu Lys 1055 1060 1065Glu Ala His Ala Trp Leu Gln Ala Gly Lys Ile Tyr Tyr Ile Leu 1070 1075 1080Arg Gln Ser Glu Leu Val Asp Leu Tyr Ile Gln Val Ala Gln Asn 1085 1090 1095Val Ala Leu Tyr Thr Gly Asp Pro Asn Leu Gly Leu Glu Leu Phe 1100 1105 1110Glu Ala Ala Gly Asp Ile Phe Phe Asp Gly Ala Trp Glu Arg Glu 1115 1120 1125Lys Ala Val Ser Phe Tyr Arg Asp Arg Ala Leu Pro Leu Ala Val 1130 1135 1140Thr Thr Gly Asn Arg Lys Ala Glu Leu Arg Leu Cys Asn Lys Leu 1145 1150 1155Val Ala Leu Leu Ala Thr Leu Glu Glu Pro Gln Glu Gly Leu Glu 1160 1165 1170Phe Ala His Met Ala Leu Ala Leu Ser Ile Thr Leu Gly Asp Arg 1175 1180 1185Leu Asn Glu Arg Val Ala Tyr His Arg Leu Ala Ala Leu Gln His 1190 1195 1200Arg Leu Gly His Gly Glu Leu Ala Glu His Phe Tyr Leu Lys Ala 1205 1210 1215Leu Ser Leu Cys Asn Ser Pro Leu Glu Phe Asp Glu Glu Thr Leu 1220 1225 1230Tyr Tyr Val Lys Val Tyr Leu Val Leu Gly Asp Ile Ile Phe Tyr 1235 1240 1245Asp Leu Lys Asp Pro Phe Asp Ala Ala Gly Tyr Tyr Gln Leu Ala 1250 1255 1260Leu Ala Ala Ala Val Asp Leu Gly Asn Lys Lys Ala Gln Leu Lys 1265 1270 1275Ile Tyr Thr Arg Leu Ala Thr Ile Tyr His Asn Phe Leu Leu Asp 1280 1285 1290Arg Glu Lys Ser Leu Phe Phe Tyr Gln Lys Ala Arg Thr Phe Ala 1295 1300 1305Thr Glu Leu Asn Val Arg Arg Val Asn Leu Pro Pro Leu Pro Leu 1310 1315 1320Cys Gly Trp Ala Pro Trp Leu Ala Pro Ser His Pro Arg 1325 1330 1335201120PRTHomo sapiens 20Met Trp Leu Lys Pro Glu Glu Val Leu Leu Lys Asn Ala Leu Lys Leu1 5 10 15Trp Leu Met Glu Arg Ser Asn Asp Tyr Phe Val Leu Gln Arg Arg Arg 20 25 30Gly Tyr Gly Glu Glu Gly Gly Gly Gly Leu Thr Gly Leu Leu Val Gly 35 40 45Thr Leu Asp Ser Val Leu Asp Ser Thr Ala Lys Val Ala Pro Phe Arg 50 55 60Ile Leu His Gln Thr Pro Asp Ser Gln Val Tyr Leu Ser Ile Ala Cys65 70 75 80Gly Ala Asn Arg Glu Glu Ile Thr Lys His Trp Asp Trp Leu Glu Gln 85 90 95Asn Ile Met Lys Thr Leu Ser Val Phe Asp Ser Asn Glu Asp Ile Thr 100 105 110Asn Phe Val Gln Gly Lys Ile Arg Gly Leu Ile Ala Glu Glu Gly Lys

115 120 125His Cys Phe Ala Lys Glu Asp Asp Pro Glu Lys Phe Arg Glu Ala Leu 130 135 140Leu Lys Phe Glu Lys Cys Phe Gly Leu Pro Glu Lys Glu Lys Leu Val145 150 155 160Thr Tyr Tyr Ser Cys Ser Tyr Trp Lys Gly Arg Val Pro Cys Gln Gly 165 170 175Trp Leu Tyr Leu Ser Thr Asn Phe Leu Ser Phe Tyr Ser Phe Leu Leu 180 185 190Gly Ser Glu Ile Lys Leu Ile Ile Ser Trp Asp Glu Val Ser Lys Leu 195 200 205Glu Lys Thr Ser Asn Val Ile Leu Thr Glu Ser Ile His Val Cys Ser 210 215 220Gln Gly Glu Asn His Tyr Phe Ser Met Phe Leu His Ile Asn Gln Thr225 230 235 240Tyr Leu Leu Met Glu Gln Leu Ala Asn Tyr Ala Ile Arg Arg Leu Phe 245 250 255Asp Lys Glu Thr Phe Asp Asn Asp Pro Val Leu Tyr Asn Pro Leu Gln 260 265 270Ile Thr Lys Arg Gly Leu Glu Asn Arg Ala His Ser Glu Gln Phe Asn 275 280 285Ala Phe Phe Arg Leu Pro Lys Gly Glu Ser Leu Lys Glu Val His Glu 290 295 300Cys Phe Leu Trp Val Pro Phe Ser His Phe Asn Thr His Gly Lys Met305 310 315 320Cys Ile Ser Glu Asn Tyr Ile Cys Phe Ala Ser Gln Asp Gly Asn Gln 325 330 335Cys Ser Val Ile Ile Pro Leu Arg Glu Val Leu Ala Ile Asp Lys Thr 340 345 350Asn Asp Ser Ser Lys Ser Val Ile Ile Ser Ile Lys Gly Lys Thr Ala 355 360 365Phe Arg Phe His Glu Val Lys Asp Phe Glu Gln Leu Val Ala Lys Leu 370 375 380Arg Leu Arg Cys Gly Ala Ala Ser Thr Gln Tyr His Asp Ile Ser Thr385 390 395 400Glu Leu Ala Ile Ser Ser Glu Ser Thr Glu Pro Ser Asp Asn Phe Glu 405 410 415Val Gln Ser Leu Thr Ser Gln Arg Glu Cys Ser Lys Thr Val Asn Thr 420 425 430Glu Ala Leu Met Thr Val Phe His Pro Gln Asn Leu Glu Thr Leu Asn 435 440 445Ser Lys Met Leu Lys Glu Lys Met Lys Glu Gln Ser Trp Lys Ile Leu 450 455 460Phe Ala Glu Cys Gly Arg Gly Val Ser Met Phe Arg Thr Lys Lys Thr465 470 475 480Arg Asp Leu Val Val Arg Gly Ile Pro Glu Thr Leu Arg Gly Glu Leu 485 490 495Trp Met Leu Phe Ser Gly Ala Val Asn Asp Met Ala Thr Asn Pro Asp 500 505 510Tyr Tyr Thr Glu Val Val Glu Gln Ser Leu Gly Thr Cys Asn Leu Ala 515 520 525Thr Glu Glu Ile Glu Arg Asp Leu Arg Arg Ser Leu Pro Glu His Pro 530 535 540Ala Phe Gln Ser Asp Thr Gly Ile Ser Ala Leu Arg Arg Val Leu Thr545 550 555 560Ala Tyr Ala Tyr Arg Asn Pro Lys Ile Gly Tyr Cys Gln Ala Met Asn 565 570 575Ile Leu Thr Ser Val Leu Leu Leu Tyr Ala Lys Glu Glu Glu Ala Phe 580 585 590Trp Leu Leu Val Ala Val Cys Glu Arg Met Leu Pro Asp Tyr Phe Asn 595 600 605Arg Arg Ile Ile Gly Ala Leu Val Asp Gln Ala Val Phe Glu Glu Leu 610 615 620Ile Arg Asp His Leu Pro Gln Leu Thr Glu His Met Thr Asp Met Thr625 630 635 640Phe Phe Ser Ser Val Ser Leu Ser Trp Phe Leu Thr Leu Phe Ile Ser 645 650 655Val Leu Pro Ile Glu Ser Ala Val Asn Val Val Asp Cys Phe Phe Tyr 660 665 670Asp Gly Ile Lys Ala Ile Leu Gln Leu Gly Leu Ala Ile Leu Asp Tyr 675 680 685Asn Leu Asp Lys Leu Leu Thr Cys Lys Asp Asp Ala Glu Ala Val Thr 690 695 700Ala Leu Asn Arg Phe Phe Asp Asn Val Thr Asn Lys Asp Ser Pro Leu705 710 715 720Pro Ser Asn Val Gln Gln Gly Ser Asn Val Ser Asp Glu Lys Thr Ser 725 730 735His Thr Arg Val Asp Ile Thr Asp Leu Ile Arg Glu Ser Asn Glu Lys 740 745 750Tyr Gly Asn Ile Arg Tyr Glu Asp Ile His Ser Met Arg Cys Arg Asn 755 760 765Arg Leu Tyr Val Ile Gln Thr Leu Glu Glu Thr Thr Lys Gln Asn Val 770 775 780Leu Arg Val Val Ser Gln Asp Val Lys Leu Ser Leu Gln Glu Leu Asp785 790 795 800Glu Leu Tyr Val Ile Phe Lys Lys Glu Leu Phe Leu Ser Cys Tyr Trp 805 810 815Cys Leu Gly Cys Pro Val Leu Lys His His Asp Pro Ser Leu Pro Tyr 820 825 830Leu Glu Gln Tyr Gln Ile Asp Cys Gln Gln Phe Arg Ala Leu Tyr His 835 840 845Leu Leu Ser Pro Trp Ala His Ser Ala Asn Lys Asp Ser Leu Ala Leu 850 855 860Trp Thr Phe Arg Leu Leu Asp Glu Asn Ser Asp Cys Leu Ile Asn Phe865 870 875 880Lys Glu Phe Ser Ser Ala Ile Asp Ile Met Tyr Asn Gly Ser Phe Thr 885 890 895Glu Lys Leu Lys Leu Leu Phe Lys Leu His Ile Pro Pro Ala Tyr Thr 900 905 910Glu Val Lys Ser Lys Asp Ala Ser Lys Gly Asp Glu Leu Ser Lys Glu 915 920 925Glu Leu Leu Tyr Phe Ser Gln Leu His Val Ser Lys Pro Ala Asn Glu 930 935 940Lys Glu Ala Glu Ser Ala Lys His Ser Pro Glu Lys Gly Lys Gly Lys945 950 955 960Ile Asp Ile Gln Ala Tyr Leu Ser Gln Trp Gln Asp Glu Leu Phe Lys 965 970 975Lys Glu Glu Asn Ile Lys Asp Leu Pro Arg Met Asn Gln Ser Gln Phe 980 985 990Ile Gln Phe Ser Lys Thr Leu Tyr Asn Leu Phe His Glu Asp Pro Glu 995 1000 1005Glu Glu Ser Leu Tyr Gln Ala Ile Ala Val Val Thr Ser Leu Leu 1010 1015 1020Leu Arg Met Glu Glu Val Gly Arg Lys Leu His Ser Pro Thr Ser 1025 1030 1035Ser Ala Lys Gly Phe Ser Gly Thr Val Cys Gly Ser Gly Gly Pro 1040 1045 1050Ser Glu Glu Lys Thr Gly Ser His Leu Glu Lys Asp Pro Cys Ser 1055 1060 1065Phe Arg Glu Glu Pro Gln Trp Ser Phe Ala Phe Glu Gln Ile Leu 1070 1075 1080Ala Ser Leu Leu Asn Glu Pro Ala Leu Val Arg Phe Phe Glu Lys 1085 1090 1095Pro Ile Asp Val Lys Ala Lys Leu Glu Asn Ala Arg Ile Ser Gln 1100 1105 1110Leu Arg Ser Arg Thr Lys Met 1115 1120212002PRTHomo sapiens 21Met Glu Gln Asp Arg Thr Asn His Val Glu Gly Asn Arg Leu Ser Pro1 5 10 15Phe Leu Ile Pro Ser Pro Pro Ile Cys Gln Thr Glu Pro Leu Ala Thr 20 25 30Lys Leu Gln Asn Gly Ser Pro Leu Pro Glu Arg Ala His Pro Glu Val 35 40 45Asn Gly Asp Thr Lys Trp His Ser Phe Lys Ser Tyr Tyr Gly Ile Pro 50 55 60Cys Met Lys Gly Ser Gln Asn Ser Arg Val Ser Pro Asp Phe Thr Gln65 70 75 80Glu Ser Arg Gly Tyr Ser Lys Cys Leu Gln Asn Gly Gly Ile Lys Arg 85 90 95Thr Val Ser Glu Pro Ser Leu Ser Gly Leu Leu Gln Ile Lys Lys Leu 100 105 110Lys Gln Asp Gln Lys Ala Asn Gly Glu Arg Arg Asn Phe Gly Val Ser 115 120 125Gln Glu Arg Asn Pro Gly Glu Ser Ser Gln Pro Asn Val Ser Asp Leu 130 135 140Ser Asp Lys Lys Glu Ser Val Ser Ser Val Ala Gln Glu Asn Ala Val145 150 155 160Lys Asp Phe Thr Ser Phe Ser Thr His Asn Cys Ser Gly Pro Glu Asn 165 170 175Pro Glu Leu Gln Ile Leu Asn Glu Gln Glu Gly Lys Ser Ala Asn Tyr 180 185 190His Asp Lys Asn Ile Val Leu Leu Lys Asn Lys Ala Val Leu Met Pro 195 200 205Asn Gly Ala Thr Val Ser Ala Ser Ser Val Glu His Thr His Gly Glu 210 215 220Leu Leu Glu Lys Thr Leu Ser Gln Tyr Tyr Pro Asp Cys Val Ser Ile225 230 235 240Ala Val Gln Lys Thr Thr Ser His Ile Asn Ala Ile Asn Ser Gln Ala 245 250 255Thr Asn Glu Leu Ser Cys Glu Ile Thr His Pro Ser His Thr Ser Gly 260 265 270Gln Ile Asn Ser Ala Gln Thr Ser Asn Ser Glu Leu Pro Pro Lys Pro 275 280 285Ala Ala Val Val Ser Glu Ala Cys Asp Ala Asp Asp Ala Asp Asn Ala 290 295 300Ser Lys Leu Ala Ala Met Leu Asn Thr Cys Ser Phe Gln Lys Pro Glu305 310 315 320Gln Leu Gln Gln Gln Lys Ser Val Phe Glu Ile Cys Pro Ser Pro Ala 325 330 335Glu Asn Asn Ile Gln Gly Thr Thr Lys Leu Ala Ser Gly Glu Glu Phe 340 345 350Cys Ser Gly Ser Ser Ser Asn Leu Gln Ala Pro Gly Gly Ser Ser Glu 355 360 365Arg Tyr Leu Lys Gln Asn Glu Met Asn Gly Ala Tyr Phe Lys Gln Ser 370 375 380Ser Val Phe Thr Lys Asp Ser Phe Ser Ala Thr Thr Thr Pro Pro Pro385 390 395 400Pro Ser Gln Leu Leu Leu Ser Pro Pro Pro Pro Leu Pro Gln Val Pro 405 410 415Gln Leu Pro Ser Glu Gly Lys Ser Thr Leu Asn Gly Gly Val Leu Glu 420 425 430Glu His His His Tyr Pro Asn Gln Ser Asn Thr Thr Leu Leu Arg Glu 435 440 445Val Lys Ile Glu Gly Lys Pro Glu Ala Pro Pro Ser Gln Ser Pro Asn 450 455 460Pro Ser Thr His Val Cys Ser Pro Ser Pro Met Leu Ser Glu Arg Pro465 470 475 480Gln Asn Asn Cys Val Asn Arg Asn Asp Ile Gln Thr Ala Gly Thr Met 485 490 495Thr Val Pro Leu Cys Ser Glu Lys Thr Arg Pro Met Ser Glu His Leu 500 505 510Lys His Asn Pro Pro Ile Phe Gly Ser Ser Gly Glu Leu Gln Asp Asn 515 520 525Cys Gln Gln Leu Met Arg Asn Lys Glu Gln Glu Ile Leu Lys Gly Arg 530 535 540Asp Lys Glu Gln Thr Arg Asp Leu Val Pro Pro Thr Gln His Tyr Leu545 550 555 560Lys Pro Gly Trp Ile Glu Leu Lys Ala Pro Arg Phe His Gln Ala Glu 565 570 575Ser His Leu Lys Arg Asn Glu Ala Ser Leu Pro Ser Ile Leu Gln Tyr 580 585 590Gln Pro Asn Leu Ser Asn Gln Met Thr Ser Lys Gln Tyr Thr Gly Asn 595 600 605Ser Asn Met Pro Gly Gly Leu Pro Arg Gln Ala Tyr Thr Gln Lys Thr 610 615 620Thr Gln Leu Glu His Lys Ser Gln Met Tyr Gln Val Glu Met Asn Gln625 630 635 640Gly Gln Ser Gln Gly Thr Val Asp Gln His Leu Gln Phe Gln Lys Pro 645 650 655Ser His Gln Val His Phe Ser Lys Thr Asp His Leu Pro Lys Ala His 660 665 670Val Gln Ser Leu Cys Gly Thr Arg Phe His Phe Gln Gln Arg Ala Asp 675 680 685Ser Gln Thr Glu Lys Leu Met Ser Pro Val Leu Lys Gln His Leu Asn 690 695 700Gln Gln Ala Ser Glu Thr Glu Pro Phe Ser Asn Ser His Leu Leu Gln705 710 715 720His Lys Pro His Lys Gln Ala Ala Gln Thr Gln Pro Ser Gln Ser Ser 725 730 735His Leu Pro Gln Asn Gln Gln Gln Gln Gln Lys Leu Gln Ile Lys Asn 740 745 750Lys Glu Glu Ile Leu Gln Thr Phe Pro His Pro Gln Ser Asn Asn Asp 755 760 765Gln Gln Arg Glu Gly Ser Phe Phe Gly Gln Thr Lys Val Glu Glu Cys 770 775 780Phe His Gly Glu Asn Gln Tyr Ser Lys Ser Ser Glu Phe Glu Thr His785 790 795 800Asn Val Gln Met Gly Leu Glu Glu Val Gln Asn Ile Asn Arg Arg Asn 805 810 815Ser Pro Tyr Ser Gln Thr Met Lys Ser Ser Ala Cys Lys Ile Gln Val 820 825 830Ser Cys Ser Asn Asn Thr His Leu Val Ser Glu Asn Lys Glu Gln Thr 835 840 845Thr His Pro Glu Leu Phe Ala Gly Asn Lys Thr Gln Asn Leu His His 850 855 860Met Gln Tyr Phe Pro Asn Asn Val Ile Pro Lys Gln Asp Leu Leu His865 870 875 880Arg Cys Phe Gln Glu Gln Glu Gln Lys Ser Gln Gln Ala Ser Val Leu 885 890 895Gln Gly Tyr Lys Asn Arg Asn Gln Asp Met Ser Gly Gln Gln Ala Ala 900 905 910Gln Leu Ala Gln Gln Arg Tyr Leu Ile His Asn His Ala Asn Val Phe 915 920 925Pro Val Pro Asp Gln Gly Gly Ser His Thr Gln Thr Pro Pro Gln Lys 930 935 940Asp Thr Gln Lys His Ala Ala Leu Arg Trp His Leu Leu Gln Lys Gln945 950 955 960Glu Gln Gln Gln Thr Gln Gln Pro Gln Thr Glu Ser Cys His Ser Gln 965 970 975Met His Arg Pro Ile Lys Val Glu Pro Gly Cys Lys Pro His Ala Cys 980 985 990Met His Thr Ala Pro Pro Glu Asn Lys Thr Trp Lys Lys Val Thr Lys 995 1000 1005Gln Glu Asn Pro Pro Ala Ser Cys Asp Asn Val Gln Gln Lys Ser 1010 1015 1020Ile Ile Glu Thr Met Glu Gln His Leu Lys Gln Phe His Ala Lys 1025 1030 1035Ser Leu Phe Asp His Lys Ala Leu Thr Leu Lys Ser Gln Lys Gln 1040 1045 1050Val Lys Val Glu Met Ser Gly Pro Val Thr Val Leu Thr Arg Gln 1055 1060 1065Thr Thr Ala Ala Glu Leu Asp Ser His Thr Pro Ala Leu Glu Gln 1070 1075 1080Gln Thr Thr Ser Ser Glu Lys Thr Pro Thr Lys Arg Thr Ala Ala 1085 1090 1095Ser Val Leu Asn Asn Phe Ile Glu Ser Pro Ser Lys Leu Leu Asp 1100 1105 1110Thr Pro Ile Lys Asn Leu Leu Asp Thr Pro Val Lys Thr Gln Tyr 1115 1120 1125Asp Phe Pro Ser Cys Arg Cys Val Glu Gln Ile Ile Glu Lys Asp 1130 1135 1140Glu Gly Pro Phe Tyr Thr His Leu Gly Ala Gly Pro Asn Val Ala 1145 1150 1155Ala Ile Arg Glu Ile Met Glu Glu Arg Phe Gly Gln Lys Gly Lys 1160 1165 1170Ala Ile Arg Ile Glu Arg Val Ile Tyr Thr Gly Lys Glu Gly Lys 1175 1180 1185Ser Ser Gln Gly Cys Pro Ile Ala Lys Trp Val Val Arg Arg Ser 1190 1195 1200Ser Ser Glu Glu Lys Leu Leu Cys Leu Val Arg Glu Arg Ala Gly 1205 1210 1215His Thr Cys Glu Ala Ala Val Ile Val Ile Leu Ile Leu Val Trp 1220 1225 1230Glu Gly Ile Pro Leu Ser Leu Ala Asp Lys Leu Tyr Ser Glu Leu 1235 1240 1245Thr Glu Thr Leu Arg Lys Tyr Gly Thr Leu Thr Asn Arg Arg Cys 1250 1255 1260Ala Leu Asn Glu Glu Arg Thr Cys Ala Cys Gln Gly Leu Asp Pro 1265 1270 1275Glu Thr Cys Gly Ala Ser Phe Ser Phe Gly Cys Ser Trp Ser Met 1280 1285 1290Tyr Tyr Asn Gly Cys Lys Phe Ala Arg Ser Lys Ile Pro Arg Lys 1295 1300 1305Phe Lys Leu Leu Gly Asp Asp Pro Lys Glu Glu Glu Lys Leu Glu 1310 1315 1320Ser His Leu Gln Asn Leu Ser Thr Leu Met Ala Pro Thr Tyr Lys 1325 1330 1335Lys Leu Ala Pro Asp Ala Tyr Asn Asn Gln Ile Glu Tyr Glu His 1340 1345 1350Arg Ala Pro Glu Cys Arg Leu Gly Leu Lys Glu Gly Arg Pro Phe 1355 1360 1365Ser Gly Val Thr Ala Cys Leu Asp Phe Cys Ala His Ala His Arg 1370 1375 1380Asp Leu His Asn Met Gln Asn Gly Ser Thr Leu Val Cys Thr Leu 1385 1390 1395Thr Arg Glu Asp Asn Arg Glu Phe Gly Gly Lys Pro Glu Asp Glu 1400 1405 1410Gln Leu His Val Leu Pro Leu Tyr Lys Val Ser Asp Val Asp Glu 1415 1420 1425Phe Gly Ser Val Glu Ala Gln Glu Glu Lys Lys Arg Ser Gly Ala 1430 1435 1440Ile Gln Val Leu Ser Ser Phe Arg Arg Lys Val Arg Met Leu Ala 1445 1450 1455Glu Pro Val Lys Thr Cys

Arg Gln Arg Lys Leu Glu Ala Lys Lys 1460 1465 1470Ala Ala Ala Glu Lys Leu Ser Ser Leu Glu Asn Ser Ser Asn Lys 1475 1480 1485Asn Glu Lys Glu Lys Ser Ala Pro Ser Arg Thr Lys Gln Thr Glu 1490 1495 1500Asn Ala Ser Gln Ala Lys Gln Leu Ala Glu Leu Leu Arg Leu Ser 1505 1510 1515Gly Pro Val Met Gln Gln Ser Gln Gln Pro Gln Pro Leu Gln Lys 1520 1525 1530Gln Pro Pro Gln Pro Gln Gln Gln Gln Arg Pro Gln Gln Gln Gln 1535 1540 1545Pro His His Pro Gln Thr Glu Ser Val Asn Ser Tyr Ser Ala Ser 1550 1555 1560Gly Ser Thr Asn Pro Tyr Met Arg Arg Pro Asn Pro Val Ser Pro 1565 1570 1575Tyr Pro Asn Ser Ser His Thr Ser Asp Ile Tyr Gly Ser Thr Ser 1580 1585 1590Pro Met Asn Phe Tyr Ser Thr Ser Ser Gln Ala Ala Gly Ser Tyr 1595 1600 1605Leu Asn Ser Ser Asn Pro Met Asn Pro Tyr Pro Gly Leu Leu Asn 1610 1615 1620Gln Asn Thr Gln Tyr Pro Ser Tyr Gln Cys Asn Gly Asn Leu Ser 1625 1630 1635Val Asp Asn Cys Ser Pro Tyr Leu Gly Ser Tyr Ser Pro Gln Ser 1640 1645 1650Gln Pro Met Asp Leu Tyr Arg Tyr Pro Ser Gln Asp Pro Leu Ser 1655 1660 1665Lys Leu Ser Leu Pro Pro Ile His Thr Leu Tyr Gln Pro Arg Phe 1670 1675 1680Gly Asn Ser Gln Ser Phe Thr Ser Lys Tyr Leu Gly Tyr Gly Asn 1685 1690 1695Gln Asn Met Gln Gly Asp Gly Phe Ser Ser Cys Thr Ile Arg Pro 1700 1705 1710Asn Val His His Val Gly Lys Leu Pro Pro Tyr Pro Thr His Glu 1715 1720 1725Met Asp Gly His Phe Met Gly Ala Thr Ser Arg Leu Pro Pro Asn 1730 1735 1740Leu Ser Asn Pro Asn Met Asp Tyr Lys Asn Gly Glu His His Ser 1745 1750 1755Pro Ser His Ile Ile His Asn Tyr Ser Ala Ala Pro Gly Met Phe 1760 1765 1770Asn Ser Ser Leu His Ala Leu His Leu Gln Asn Lys Glu Asn Asp 1775 1780 1785Met Leu Ser His Thr Ala Asn Gly Leu Ser Lys Met Leu Pro Ala 1790 1795 1800Leu Asn His Asp Arg Thr Ala Cys Val Gln Gly Gly Leu His Lys 1805 1810 1815Leu Ser Asp Ala Asn Gly Gln Glu Lys Gln Pro Leu Ala Leu Val 1820 1825 1830Gln Gly Val Ala Ser Gly Ala Glu Asp Asn Asp Glu Val Trp Ser 1835 1840 1845Asp Ser Glu Gln Ser Phe Leu Asp Pro Asp Ile Gly Gly Val Ala 1850 1855 1860Val Ala Pro Thr His Gly Ser Ile Leu Ile Glu Cys Ala Lys Arg 1865 1870 1875Glu Leu His Ala Thr Thr Pro Leu Lys Asn Pro Asn Arg Asn His 1880 1885 1890Pro Thr Arg Ile Ser Leu Val Phe Tyr Gln His Lys Ser Met Asn 1895 1900 1905Glu Pro Lys His Gly Leu Ala Leu Trp Glu Ala Lys Met Ala Glu 1910 1915 1920Lys Ala Arg Glu Lys Glu Glu Glu Cys Glu Lys Tyr Gly Pro Asp 1925 1930 1935Tyr Val Pro Gln Lys Ser His Gly Lys Lys Val Lys Arg Glu Pro 1940 1945 1950Ala Glu Pro His Glu Thr Ser Glu Pro Thr Tyr Leu Arg Phe Ile 1955 1960 1965Lys Ser Leu Ala Glu Arg Thr Met Ser Val Thr Thr Asp Ser Thr 1970 1975 1980Val Thr Thr Ser Pro Tyr Ala Phe Thr Arg Val Thr Gly Pro Tyr 1985 1990 1995Asn Arg Tyr Ile 200022409PRTHomo sapiens 22Met Ala Leu Arg Pro Glu Asp Pro Ser Ser Gly Phe Arg His Ser Asn1 5 10 15Val Val Ala Phe Ile Asn Glu Lys Met Ala Arg His Thr Lys Gly Pro 20 25 30Glu Phe Tyr Leu Glu Asn Ile Ser Leu Ser Trp Glu Lys Val Glu Asp 35 40 45Lys Leu Arg Ala Ile Leu Glu Asp Ser Glu Val Pro Ser Glu Val Lys 50 55 60Glu Ala Cys Thr Trp Gly Ser Leu Ala Leu Gly Val Arg Phe Ala His65 70 75 80Arg Gln Ala Gln Leu Gln Arg His Arg Val Arg Trp Leu His Gly Phe 85 90 95Ala Lys Leu His Lys Ser Ala Ala Gln Ala Leu Ala Ser Asp Leu Lys 100 105 110Lys Leu Arg Glu Gln Gln Glu Thr Glu Arg Lys Glu Ala Ala Ser Arg 115 120 125Leu Arg Met Ala Gln Thr Ser Leu Val Glu Val Gln Lys Glu Arg Asp 130 135 140Lys Glu Leu Val Ser Pro His Glu Trp Glu Gln Gly Ala Gly Trp Pro145 150 155 160Gly Leu Ala Thr Ala Gly Gly Val Cys Thr Glu Gly Ala Ala Glu Glu 165 170 175Glu Glu Glu Ala Ala Val Ala Ala Ala Gly Ala Ala Gly Gly Lys Gly 180 185 190Ala Glu Glu Glu Gln Arg Asp Val Glu Val Val Ala Ala Pro Val Glu 195 200 205Ala Met Ala Pro Pro Val Glu Ala Gly Ala Ala Pro Met Glu Thr Gln 210 215 220Phe Pro His Val Glu Ala Arg Ala Ala Ser Met Glu Thr Thr Glu Lys225 230 235 240Leu Glu Arg Ile Leu Leu Gln Leu Leu Gly Asp Ala Asp Gln Glu Lys 245 250 255Tyr Thr Tyr Trp Gly Gln Lys Glu Gly Asp Leu Arg Ser Val Glu Thr 260 265 270Ala Thr Ser Tyr Phe Ser Gly Thr Thr Asn Pro Trp Ser Arg Ala Ser 275 280 285Ser Glu Pro Leu Pro Val Gln Leu Pro Ala Ser Tyr Ser Tyr Ser Tyr 290 295 300Ser Ser Pro Phe Ser Ser Phe Ser Asp Ile Pro Thr Ile Ser Pro Pro305 310 315 320Gln Ala Thr Val Thr Ala Pro Val Pro Pro Gln Leu Pro Ser Asp Trp 325 330 335Glu Ala Phe Asp Thr Ser Leu Trp Ser Asp Gly Gly Pro His Arg Ile 340 345 350Asp His Gln Glu His Pro Arg Asp Arg Arg Tyr Ser Glu Pro His Gln 355 360 365Gln Arg Pro Pro Val Tyr Arg Arg Pro Gly Asp Trp Asp Cys Pro Trp 370 375 380Cys Asn Ala Val Asn Phe Ser Arg Arg Asp Thr Cys Phe Asp Cys Gly385 390 395 400Lys Gly Ile Trp Leu Gln Lys Pro His 40523472PRTHomo sapiens 23Met Ala Gly Pro Gly Trp Gly Pro Pro Arg Leu Asp Gly Phe Ile Leu1 5 10 15Thr Glu Arg Leu Gly Ser Gly Thr Tyr Ala Thr Val Tyr Lys Ala Tyr 20 25 30Ala Lys Lys Asp Thr Arg Glu Val Val Ala Ile Lys Cys Val Ala Lys 35 40 45Lys Ser Leu Asn Lys Ala Ser Val Glu Asn Leu Leu Thr Glu Ile Glu 50 55 60Ile Leu Lys Gly Ile Arg His Pro His Ile Val Gln Leu Lys Asp Phe65 70 75 80Gln Trp Asp Ser Asp Asn Ile Tyr Leu Ile Met Glu Phe Cys Ala Gly 85 90 95Gly Asp Leu Ser Arg Phe Ile His Thr Arg Arg Ile Leu Pro Glu Lys 100 105 110Val Ala Arg Val Phe Met Gln Gln Leu Ala Ser Ala Leu Gln Phe Leu 115 120 125His Glu Arg Asn Ile Ser His Leu Asp Leu Lys Pro Gln Asn Ile Leu 130 135 140Leu Ser Ser Leu Glu Lys Pro His Leu Lys Leu Ala Asp Phe Gly Phe145 150 155 160Ala Gln His Met Ser Pro Trp Asp Glu Lys His Val Leu Arg Gly Ser 165 170 175Pro Leu Tyr Met Ala Pro Glu Met Val Cys Gln Arg Gln Tyr Asp Ala 180 185 190Arg Val Asp Leu Trp Ser Met Gly Val Ile Leu Tyr Glu Ala Leu Phe 195 200 205Gly Gln Pro Pro Phe Ala Ser Arg Ser Phe Ser Glu Leu Glu Glu Lys 210 215 220Ile Arg Ser Asn Arg Val Ile Glu Leu Pro Leu Arg Pro Leu Leu Ser225 230 235 240Arg Asp Cys Arg Asp Leu Leu Gln Arg Leu Leu Glu Arg Asp Pro Ser 245 250 255Arg Arg Ile Ser Phe Gln Asp Phe Phe Ala His Pro Trp Val Asp Leu 260 265 270Glu His Met Pro Ser Gly Glu Ser Leu Gly Arg Ala Thr Ala Leu Val 275 280 285Val Gln Ala Val Lys Lys Asp Gln Glu Gly Asp Ser Ala Ala Ala Leu 290 295 300Ser Leu Tyr Cys Lys Ala Leu Asp Phe Phe Val Pro Ala Leu His Tyr305 310 315 320Glu Val Asp Ala Gln Arg Lys Glu Ala Ile Lys Ala Lys Val Gly Gln 325 330 335Tyr Val Ser Arg Ala Glu Glu Leu Lys Ala Ile Val Ser Ser Ser Asn 340 345 350Gln Ala Leu Leu Arg Gln Gly Thr Ser Ala Arg Asp Leu Leu Arg Glu 355 360 365Met Ala Arg Asp Lys Pro Arg Leu Leu Ala Ala Leu Glu Val Ala Ser 370 375 380Ala Ala Met Ala Lys Glu Glu Ala Ala Gly Gly Glu Gln Asp Ala Leu385 390 395 400Asp Leu Tyr Gln His Ser Leu Gly Glu Leu Leu Leu Leu Leu Ala Ala 405 410 415Glu Pro Pro Gly Arg Arg Arg Glu Leu Leu His Thr Glu Val Gln Asn 420 425 430Leu Met Ala Arg Ala Glu Tyr Leu Lys Glu Gln Val Lys Met Arg Glu 435 440 445Ser Arg Trp Glu Ala Asp Thr Leu Asp Lys Glu Gly Leu Ser Glu Ser 450 455 460Val Arg Ser Ser Cys Thr Leu Gln465 470241743PRTHomo sapiens 24Met Ala Thr Asp Ser Gly Asp Pro Ala Ser Thr Glu Asp Ser Glu Lys1 5 10 15Pro Asp Gly Ile Ser Phe Glu Asn Arg Val Pro Gln Val Ala Ala Thr 20 25 30Leu Thr Val Glu Ala Arg Leu Lys Glu Lys Asn Ser Thr Phe Ser Ala 35 40 45Ser Gly Glu Thr Val Glu Arg Lys Arg Phe Phe Arg Lys Ser Val Glu 50 55 60Met Thr Glu Asp Asp Lys Val Ala Glu Ser Ser Pro Lys Asp Glu Arg65 70 75 80Ile Lys Ala Ala Met Asn Ile Pro Arg Val Asp Lys Leu Pro Ser Asn 85 90 95Val Leu Arg Gly Gly Gln Glu Val Lys Tyr Glu Gln Cys Ser Lys Ser 100 105 110Thr Ser Glu Ile Ser Lys Asp Cys Phe Lys Glu Lys Asn Glu Lys Glu 115 120 125Met Glu Glu Glu Ala Glu Met Lys Ala Val Ala Thr Ser Pro Ser Gly 130 135 140Arg Phe Leu Lys Phe Asp Ile Glu Leu Gly Arg Gly Ala Phe Lys Thr145 150 155 160Val Tyr Lys Gly Leu Asp Thr Glu Thr Trp Val Glu Val Ala Trp Cys 165 170 175Glu Leu Gln Asp Arg Lys Leu Thr Lys Ala Glu Gln Gln Arg Phe Lys 180 185 190Glu Glu Ala Glu Met Leu Lys Gly Leu Gln His Pro Asn Ile Val Arg 195 200 205Phe Tyr Asp Ser Trp Glu Ser Ile Leu Lys Gly Lys Lys Cys Ile Val 210 215 220Leu Val Thr Glu Leu Met Thr Ser Gly Thr Leu Lys Thr Tyr Leu Lys225 230 235 240Arg Phe Lys Val Met Lys Pro Lys Val Leu Arg Ser Trp Cys Arg Gln 245 250 255Ile Leu Lys Gly Leu Gln Phe Leu His Thr Arg Thr Pro Pro Ile Ile 260 265 270His Arg Asp Leu Lys Cys Asp Asn Ile Phe Ile Thr Gly Pro Thr Gly 275 280 285Ser Val Lys Ile Gly Asp Leu Gly Leu Ala Thr Leu Met Arg Thr Ser 290 295 300Phe Ala Lys Ser Val Ile Gly Thr Pro Glu Phe Met Ala Pro Glu Met305 310 315 320Tyr Glu Glu His Tyr Asp Glu Ser Val Asp Val Tyr Ala Phe Gly Met 325 330 335Cys Met Leu Glu Met Ala Thr Ser Glu Tyr Pro Tyr Ser Glu Cys Gln 340 345 350Asn Ala Ala Gln Ile Tyr Arg Lys Val Thr Ser Gly Ile Lys Pro Ala 355 360 365Ser Phe Asn Lys Val Thr Asp Pro Glu Val Lys Glu Ile Ile Glu Gly 370 375 380Cys Ile Arg Gln Asn Lys Ser Glu Arg Leu Ser Ile Arg Asp Leu Leu385 390 395 400Asn His Ala Phe Phe Ala Glu Asp Thr Gly Leu Arg Val Glu Leu Ala 405 410 415Glu Glu Asp Asp Cys Ser Asn Ser Ser Leu Ala Leu Arg Leu Trp Val 420 425 430Glu Asp Pro Lys Lys Leu Lys Gly Lys His Lys Asp Asn Glu Ala Ile 435 440 445Glu Phe Ser Phe Asn Leu Glu Thr Asp Thr Pro Glu Glu Val Ala Tyr 450 455 460Glu Met Val Lys Ser Gly Phe Phe His Glu Ser Asp Ser Lys Ala Val465 470 475 480Ala Lys Ser Ile Arg Asp Arg Val Thr Pro Ile Lys Lys Thr Arg Glu 485 490 495Lys Lys Pro Ala Gly Cys Leu Glu Glu Arg Arg Asp Ser Gln Cys Lys 500 505 510Ser Met Gly Asn Val Phe Pro Gln Pro Gln Asn Thr Thr Leu Pro Leu 515 520 525Ala Pro Ala Gln Gln Thr Gly Ala Glu Cys Glu Glu Thr Glu Val Asp 530 535 540Gln His Val Arg Gln Gln Leu Leu Gln Arg Lys Pro Gln Gln His Cys545 550 555 560Ser Ser Val Thr Gly Asp Asn Leu Ser Glu Ala Gly Ala Ala Ser Val 565 570 575Ile His Ser Asp Thr Ser Ser Gln Pro Ser Val Ala Tyr Ser Ser Asn 580 585 590Gln Thr Met Gly Ser Gln Met Val Ser Asn Ile Pro Gln Ala Glu Val 595 600 605Asn Val Pro Gly Gln Ile Tyr Ser Ser Gln Gln Leu Val Gly His Tyr 610 615 620Gln Gln Val Ser Gly Leu Gln Lys His Ser Lys Leu Thr Gln Pro Gln625 630 635 640Ile Leu Pro Leu Val Gln Gly Gln Ser Thr Val Leu Pro Val His Val 645 650 655Leu Gly Pro Thr Val Val Ser Gln Pro Gln Val Ser Pro Leu Thr Val 660 665 670Gln Lys Val Pro Gln Ile Lys Pro Val Ser Gln Pro Val Gly Ala Glu 675 680 685Gln Gln Ala Ala Leu Leu Lys Pro Asp Leu Val Arg Ser Leu Asn Gln 690 695 700Asp Val Ala Thr Thr Lys Glu Asn Val Ser Ser Pro Asp Asn Pro Ser705 710 715 720Gly Asn Gly Lys Gln Asp Arg Ile Lys Gln Arg Arg Ala Ser Cys Pro 725 730 735Arg Pro Glu Lys Gly Thr Lys Phe Gln Leu Thr Val Leu Gln Val Ser 740 745 750Thr Ser Gly Asp Asn Met Val Glu Cys Gln Leu Glu Thr His Asn Asn 755 760 765Lys Met Val Thr Phe Lys Phe Asp Val Asp Gly Asp Ala Pro Glu Asp 770 775 780Ile Ala Asp Tyr Met Val Glu Asp Asn Phe Val Leu Glu Ser Glu Lys785 790 795 800Glu Lys Phe Val Glu Glu Leu Arg Ala Ile Val Gly Gln Ala Gln Glu 805 810 815Ile Leu His Val His Phe Ala Thr Glu Arg Ala Thr Gly Val Asp Ser 820 825 830Ile Thr Val Asp Ser Asn Ser Ser Gln Thr Gly Ser Ser Glu Gln Val 835 840 845Gln Ile Asn Ser Thr Ser Thr Gln Thr Ser Asn Glu Ser Ala Pro Gln 850 855 860Ser Ser Pro Val Gly Arg Trp Arg Phe Cys Ile Asn Gln Thr Ile Arg865 870 875 880Asn Arg Glu Thr Gln Ser Pro Pro Ser Leu Gln His Ser Met Ser Ala 885 890 895Val Pro Gly Arg His Pro Leu Pro Ser Pro Lys Asn Thr Ser Asn Lys 900 905 910Glu Ile Ser Arg Asp Thr Leu Leu Thr Ile Glu Asn Asn Pro Cys His 915 920 925Arg Ala Leu Phe Thr Ser Lys Ser Glu His Lys Asp Val Val Asp Gly 930 935 940Lys Ile Ser Glu Cys Ala Ser Val Glu Thr Lys Gln Pro Ala Ile Leu945 950 955 960Tyr Gln Val Glu Asp Asn Arg Gln Ile Met Ala Pro Val Thr Asn Ser 965 970 975Ser Ser Tyr Ser Thr Thr Ser Val Arg Ala Val Pro Ala Glu Cys Glu 980 985 990Gly Leu Thr Lys Gln Ala Ser Ile Phe Ile Pro Val Tyr Pro Cys His 995 1000 1005Gln Thr Ala Ser Gln Ala Asp Ala Leu Met Ser His Pro Gly Glu 1010 1015 1020Ser Thr Gln Thr Ser Gly Asn Ser Leu Thr Thr Leu Ala Phe Asp 1025 1030 1035Gln Lys Pro Gln Thr

Leu Ser Val Gln Gln Pro Ala Met Asp Ala 1040 1045 1050Glu Phe Ile Ser Gln Glu Gly Glu Thr Thr Val Asn Thr Glu Ala 1055 1060 1065Ser Ser Pro Lys Thr Val Ile Pro Thr Gln Thr Pro Gly Leu Glu 1070 1075 1080Pro Thr Thr Leu Gln Pro Thr Thr Val Leu Glu Ser Asp Gly Glu 1085 1090 1095Arg Pro Pro Lys Leu Glu Phe Ala Asp Asn Arg Ile Lys Thr Leu 1100 1105 1110Asp Glu Lys Leu Arg Asn Leu Leu Tyr Gln Glu His Ser Ile Ser 1115 1120 1125Ser Ile Tyr Pro Glu Ser Gln Lys Asp Thr Gln Ser Ile Asp Ser 1130 1135 1140Pro Phe Ser Ser Ser Ala Glu Asp Thr Leu Ser Cys Pro Val Thr 1145 1150 1155Glu Val Ile Ala Ile Ser His Cys Gly Ile Lys Asp Ser Pro Val 1160 1165 1170Gln Ser Pro Asn Phe Gln Gln Thr Gly Ser Lys Leu Leu Ser Asn 1175 1180 1185Val Ala Ala Ser Gln Pro Ala Asn Ile Ser Val Phe Lys Arg Asp 1190 1195 1200Leu Asn Val Ile Thr Ser Val Pro Ser Glu Leu Cys Leu His Glu 1205 1210 1215Met Ser Ser Asp Ala Ser Leu Pro Gly Asp Pro Glu Ala Tyr Pro 1220 1225 1230Ala Ala Val Ser Ser Gly Gly Ala Ile His Leu Gln Thr Gly Val 1235 1240 1245Glu Thr Glu Glu Met Arg Ser Ala Ile Ala Pro Asp Pro Ile Pro 1250 1255 1260Leu Thr Arg Glu Ser Thr Ala Asp Thr Arg Ala Leu Asn Arg Cys 1265 1270 1275Lys Ala Met Ser Gly Ser Phe Gln Arg Gly Arg Phe Gln Val Ile 1280 1285 1290Thr Ile Pro Gln Gln Gln Ser Ala Lys Met Thr Ser Phe Gly Ile 1295 1300 1305Glu His Ile Ser Val Phe Ser Glu Thr Asn His Ser Ser Glu Glu 1310 1315 1320Ala Phe Ile Lys Thr Ala Lys Ser Gln Leu Val Glu Ile Glu Pro 1325 1330 1335Ala Thr Gln Asn Pro Lys Thr Ser Phe Ser Tyr Glu Lys Leu Gln 1340 1345 1350Ala Leu Gln Glu Thr Cys Lys Glu Asn Lys Gly Val Pro Lys Gln 1355 1360 1365Gly Asp Asn Phe Leu Ser Phe Ser Ala Ala Cys Glu Thr Asp Val 1370 1375 1380Ser Ser Val Thr Pro Glu Lys Glu Phe Glu Glu Thr Ser Ala Thr 1385 1390 1395Gly Ser Ser Met Gln Ser Gly Ser Glu Leu Leu Leu Lys Glu Arg 1400 1405 1410Glu Ile Leu Thr Ala Gly Lys Gln Pro Ser Ser Asp Ser Glu Phe 1415 1420 1425Ser Ala Ser Leu Ala Gly Ser Gly Lys Ser Val Ala Lys Thr Gly 1430 1435 1440Pro Glu Ser Asn Gln Cys Leu Pro His His Glu Glu Gln Ala Tyr 1445 1450 1455Ala Gln Thr Gln Ser Ser Leu Phe Tyr Ser Pro Ser Ser Pro Met 1460 1465 1470Ser Ser Asp Asp Glu Ser Glu Ile Glu Asp Glu Asp Leu Lys Val 1475 1480 1485Glu Leu Gln Arg Leu Arg Glu Lys His Ile Gln Glu Val Val Asn 1490 1495 1500Leu Gln Thr Gln Gln Asn Lys Glu Leu Gln Glu Leu Tyr Glu Arg 1505 1510 1515Leu Arg Ser Ile Lys Asp Ser Lys Thr Gln Ser Thr Glu Ile Pro 1520 1525 1530Leu Pro Pro Ala Ser Pro Arg Arg Pro Arg Ser Phe Lys Ser Lys 1535 1540 1545Leu Arg Ser Arg Pro Gln Ser Leu Thr His Val Asp Asn Gly Ile 1550 1555 1560Val Ala Thr Asp Pro Leu Cys Val Glu Ser Asn Ala Ala Ser Cys 1565 1570 1575Gln Gln Ser Pro Ala Ser Lys Lys Gly Met Phe Thr Asp Asp Leu 1580 1585 1590His Lys Leu Val Asp Asp Trp Thr Lys Glu Ala Val Gly Asn Ser 1595 1600 1605Leu Ile Lys Pro Ser Leu Asn Gln Leu Lys Gln Ser Gln His Lys 1610 1615 1620Leu Glu Thr Glu Asn Trp Asn Lys Val Ser Glu Asn Thr Pro Ser 1625 1630 1635Thr Met Gly Tyr Thr Ser Thr Trp Ile Ser Ser Leu Ser Gln Ile 1640 1645 1650Arg Gly Ala Val Pro Thr Ser Leu Pro Gln Gly Leu Ser Leu Pro 1655 1660 1665Ser Phe Pro Gly Pro Leu Ser Ser Tyr Gly Met Pro His Val Cys 1670 1675 1680Gln Tyr Asn Ala Val Ala Gly Ala Gly Tyr Pro Val Gln Trp Val 1685 1690 1695Gly Ile Ser Gly Thr Thr Gln Gln Ser Val Val Ile Pro Ala Gln 1700 1705 1710Ser Gly Gly Pro Phe Gln Pro Gly Met Asn Met Gln Ala Phe Pro 1715 1720 1725Thr Ser Ser Val Gln Asn Pro Ala Thr Ile Pro Pro Gly Pro Lys 1730 1735 174025590PRTHomo sapiens 25Met Arg Pro Arg Arg Pro Leu Val Phe Met Ser Leu Val Cys Ala Leu1 5 10 15Leu Asn Thr Cys Gln Ala His Arg Val His Asp Asp Lys Pro Asn Ile 20 25 30Val Leu Ile Met Val Asp Asp Leu Gly Ile Gly Asp Leu Gly Cys Tyr 35 40 45Gly Asn Asp Thr Met Arg Thr Pro His Ile Asp Arg Leu Ala Arg Glu 50 55 60Gly Val Arg Leu Thr Gln His Ile Ser Ala Ala Ser Leu Cys Ser Pro65 70 75 80Ser Arg Ser Ala Phe Leu Thr Gly Arg Tyr Pro Ile Arg Ser Gly Met 85 90 95Val Ser Ser Gly Asn Arg Arg Val Ile Gln Asn Leu Ala Val Pro Ala 100 105 110Gly Leu Pro Leu Asn Glu Thr Thr Leu Ala Ala Leu Leu Lys Lys Gln 115 120 125Gly Tyr Ser Thr Gly Leu Ile Gly Lys Trp His Gln Gly Leu Asn Cys 130 135 140Asp Ser Arg Ser Asp Gln Cys His His Pro Tyr Asn Tyr Gly Phe Asp145 150 155 160Tyr Tyr Tyr Gly Met Pro Phe Thr Leu Val Asp Ser Cys Trp Pro Asp 165 170 175Pro Ser Arg Asn Thr Glu Leu Ala Phe Glu Ser Gln Leu Trp Leu Cys 180 185 190Val Gln Leu Val Ala Ile Ala Ile Leu Thr Leu Thr Phe Gly Lys Leu 195 200 205Ser Gly Trp Val Ser Val Pro Trp Leu Leu Ile Phe Ser Met Ile Leu 210 215 220Phe Ile Phe Leu Leu Gly Tyr Ala Trp Phe Ser Ser His Thr Ser Pro225 230 235 240Leu Tyr Trp Asp Cys Leu Leu Met Arg Gly His Glu Ile Thr Glu Gln 245 250 255Pro Met Lys Ala Glu Arg Ala Gly Ser Ile Met Val Lys Glu Ala Ile 260 265 270Ser Phe Leu Glu Arg His Ser Lys Glu Thr Phe Leu Leu Phe Phe Ser 275 280 285Phe Leu His Val His Thr Pro Leu Pro Thr Thr Asp Asp Phe Thr Gly 290 295 300Thr Ser Lys His Gly Leu Tyr Gly Asp Asn Val Glu Glu Met Asp Ser305 310 315 320Met Val Gly Lys Ile Leu Asp Ala Ile Asp Asp Phe Gly Leu Arg Asn 325 330 335Asn Thr Leu Val Tyr Phe Thr Ser Asp His Gly Gly His Leu Glu Ala 340 345 350Arg Arg Gly His Ala Gln Leu Gly Gly Trp Asn Gly Ile Tyr Lys Gly 355 360 365Gly Lys Gly Met Gly Gly Trp Glu Gly Gly Ile Arg Val Pro Gly Ile 370 375 380Val Arg Trp Pro Gly Lys Val Pro Ala Gly Arg Leu Ile Lys Glu Pro385 390 395 400Thr Ser Leu Met Asp Ile Leu Pro Thr Val Ala Ser Val Ser Gly Gly 405 410 415Ser Leu Pro Gln Asp Arg Val Ile Asp Gly Arg Asp Leu Met Pro Leu 420 425 430Leu Gln Gly Asn Val Arg His Ser Glu His Glu Phe Leu Phe His Tyr 435 440 445Cys Gly Ser Tyr Leu His Ala Val Arg Trp Ile Pro Lys Asp Asp Ser 450 455 460Gly Ser Val Trp Lys Ala His Tyr Val Thr Pro Val Phe Gln Pro Pro465 470 475 480Ala Ser Gly Gly Cys Tyr Val Thr Ser Leu Cys Arg Cys Phe Gly Glu 485 490 495Gln Val Thr Tyr His Asn Pro Pro Leu Leu Phe Asp Leu Ser Arg Asp 500 505 510Pro Ser Glu Ser Thr Pro Leu Thr Pro Ala Thr Glu Pro Leu His Asp 515 520 525Phe Val Ile Lys Lys Val Ala Asn Ala Leu Lys Glu His Gln Glu Thr 530 535 540Ile Val Pro Val Thr Tyr Gln Leu Ser Glu Leu Asn Gln Gly Arg Thr545 550 555 560Trp Leu Lys Pro Cys Cys Gly Val Phe Pro Phe Cys Leu Cys Asp Lys 565 570 575Glu Glu Glu Val Ser Gln Pro Arg Gly Pro Asn Glu Lys Arg 580 585 59026469PRTHomo sapiens 26Met Ile Thr Glu Gly Ala Gln Ala Pro Arg Leu Leu Leu Pro Pro Leu1 5 10 15Leu Leu Leu Leu Thr Leu Pro Ala Thr Gly Ser Asp Pro Val Leu Cys 20 25 30Phe Thr Gln Tyr Glu Glu Ser Ser Gly Lys Cys Lys Gly Leu Leu Gly 35 40 45Gly Gly Val Ser Val Glu Asp Cys Cys Leu Asn Thr Ala Phe Ala Tyr 50 55 60Gln Lys Arg Ser Gly Gly Leu Cys Gln Pro Cys Arg Ser Pro Arg Trp65 70 75 80Ser Leu Trp Ser Thr Trp Ala Pro Cys Ser Val Thr Cys Ser Glu Gly 85 90 95Ser Gln Leu Arg Tyr Arg Arg Cys Val Gly Trp Asn Gly Gln Cys Ser 100 105 110Gly Lys Val Ala Pro Gly Thr Leu Glu Trp Gln Leu Gln Ala Cys Glu 115 120 125Asp Gln Gln Cys Cys Pro Glu Met Gly Gly Trp Ser Gly Trp Gly Pro 130 135 140Trp Glu Pro Cys Ser Val Thr Cys Ser Lys Gly Thr Arg Thr Arg Arg145 150 155 160Arg Ala Cys Asn His Pro Ala Pro Lys Cys Gly Gly His Cys Pro Gly 165 170 175Gln Ala Gln Glu Ser Glu Ala Cys Asp Thr Gln Gln Val Cys Pro Thr 180 185 190His Gly Ala Trp Ala Thr Trp Gly Pro Trp Thr Pro Cys Ser Ala Ser 195 200 205Cys His Gly Gly Pro His Glu Pro Lys Glu Thr Arg Ser Arg Lys Cys 210 215 220Ser Ala Pro Glu Pro Ser Gln Lys Pro Pro Gly Lys Pro Cys Pro Gly225 230 235 240Leu Ala Tyr Glu Gln Arg Arg Cys Thr Gly Leu Pro Pro Cys Pro Val 245 250 255Ala Gly Gly Trp Gly Pro Trp Gly Pro Val Ser Pro Cys Pro Val Thr 260 265 270Cys Gly Leu Gly Gln Thr Met Glu Gln Arg Thr Cys Asn His Pro Val 275 280 285Pro Gln His Gly Gly Pro Phe Cys Ala Gly Asp Ala Thr Arg Thr His 290 295 300Ile Cys Asn Thr Ala Val Pro Cys Pro Val Asp Gly Glu Trp Asp Ser305 310 315 320Trp Gly Glu Trp Ser Pro Cys Ile Arg Arg Asn Met Lys Ser Ile Ser 325 330 335Cys Gln Glu Ile Pro Gly Gln Gln Ser Arg Gly Arg Thr Cys Arg Gly 340 345 350Arg Lys Phe Asp Gly His Arg Cys Ala Gly Gln Gln Gln Asp Ile Arg 355 360 365His Cys Tyr Ser Ile Gln His Cys Pro Leu Lys Gly Ser Trp Ser Glu 370 375 380Trp Ser Thr Trp Gly Leu Cys Met Pro Pro Cys Gly Pro Asn Pro Thr385 390 395 400Arg Ala Arg Gln Arg Leu Cys Thr Pro Leu Leu Pro Lys Tyr Pro Pro 405 410 415Thr Val Ser Met Val Glu Gly Gln Gly Glu Lys Asn Val Thr Phe Trp 420 425 430Gly Arg Pro Leu Pro Arg Cys Glu Glu Leu Gln Gly Gln Lys Leu Val 435 440 445Val Glu Glu Lys Arg Pro Cys Leu His Val Pro Ala Cys Lys Asp Pro 450 455 460Glu Glu Glu Glu Leu46527791PRTHomo sapiens 27Met Gly Asp Gln Arg Leu Gln Asp Trp Leu Arg Ser Pro Gly Met Asp1 5 10 15Ser Lys Pro Trp Tyr Cys Asn Lys Arg Pro Ser Lys Cys Phe Ala Lys 20 25 30Cys Lys His Arg Arg Leu Arg Phe Pro Pro Met Asp Thr Gln Asn Trp 35 40 45Val Phe Val Lys Glu Gly Met Asp Asp Phe Arg Tyr Gly Cys Pro Ser 50 55 60Pro Glu Asp Thr Leu Val Cys Arg Arg Asp Glu Phe Leu Leu Pro Lys65 70 75 80Ile Ser Leu Arg Gly Pro Gln Ala Asp Pro Lys Ser Gly Gln Lys Lys 85 90 95Leu Leu Lys Lys Ala Ala Leu Phe Ser Lys Leu Ser Pro Ala Gln Leu 100 105 110Ala Arg Lys Ala Phe Val Glu Gln Val Glu Ala Gln Leu Met Ala Lys 115 120 125His Pro Leu Ala Met Tyr Pro Asn Leu Gly Glu Asp Met Pro Pro Asp 130 135 140Leu Leu Leu Gln Val Leu Lys His Leu Asp Pro Glu Arg Glu Leu Glu145 150 155 160Asp Ala Trp Ala Cys Cys Glu Thr Gln Glu Lys Thr Thr Glu Val Pro 165 170 175Thr Glu Pro Gly Lys His Pro Cys Gly Glu Phe Cys Leu Lys Pro Pro 180 185 190Glu Thr Pro Val Ser His Leu Leu Pro Glu Pro Pro Glu Thr Gly Val 195 200 205Ser His Leu Ser Pro Glu Pro Pro Lys Thr Pro Val Ser Ser Leu Arg 210 215 220Pro Glu Pro Pro Glu Thr Gly Val Ser His Leu Arg Pro Glu Pro Pro225 230 235 240Glu Thr Gly Val Ser His Ile Arg Pro Gly Pro Pro Ile Thr Arg Arg 245 250 255Arg Ser Ser Leu Leu Arg Gln Leu Leu Lys Leu Asp Ser Glu Arg Lys 260 265 270Leu Glu Asp Ala Arg Ala Pro Cys Glu Gly Arg Glu Lys Thr Thr Asp 275 280 285Glu Pro Thr Glu Pro Gly Lys Tyr Pro Cys Gly Lys Phe Cys Pro Arg 290 295 300Pro Phe Glu Thr Pro Leu Ser His Leu Arg Gln Glu Pro Pro Lys Thr305 310 315 320Pro Val Ser Ser Leu Arg Pro Glu Pro Pro Glu Thr Gly Glu Ser His 325 330 335Leu Arg Leu Glu His Ser Lys Thr Arg Arg Gly Ser Ser Leu Arg Ser 340 345 350Glu Pro Ser Glu Thr Gly Val Ser Arg Leu Arg Leu Ala Pro Pro Lys 355 360 365Thr Arg Arg Gly Ser Ser Leu His Ala Glu Pro Ser Lys Thr Gly Val 370 375 380Ser His Leu Ser Pro Glu Pro Pro Lys Thr Glu Val Ser His Leu His385 390 395 400Pro Val Pro Pro Lys Thr Gly Val Cys His Leu Arg Leu Glu Pro Pro 405 410 415Asp Thr Ser Gln Val Ser Asn Leu Leu Leu Tyr Ile Leu Lys Val Leu 420 425 430Asp Ser Gly Arg Thr Leu Lys Asp Val Trp Asp Arg Cys Glu Ala Arg 435 440 445Val Lys Lys Thr Lys Glu Pro Thr Glu Pro His Lys Ser Pro Cys Gly 450 455 460Glu Pro Cys Leu Gln Pro Pro Glu Thr Gln Val Ser His Pro His Pro465 470 475 480Glu His Pro Lys Thr Arg Arg Arg Ser Ser Leu His Ser Gln Pro Pro 485 490 495Lys Thr Arg Arg Thr Ser Ser Leu Arg Ser Glu Pro Pro Lys Thr Arg 500 505 510Arg Thr Ser Ser Leu Arg Ser Glu Pro Pro Lys Thr Arg Arg Thr Ser 515 520 525Ser Leu Gly Pro Glu Pro Pro Lys Thr Arg Arg Val Ser Ser Leu Arg 530 535 540Pro Glu Leu Pro Lys Ser Arg Arg Val Ser Ser Leu His Pro Glu Pro545 550 555 560Pro Lys Ala Pro Glu Ser His Gln Phe Ser Glu Pro Pro Lys Ile Arg 565 570 575Ala Ser Tyr Ile Lys Glu Leu Leu Gln Glu Asp Thr Pro Ser Thr Lys 580 585 590Glu Cys Val Ser Asp Ser Leu Gln Tyr Arg Tyr Thr Ser Glu Lys Leu 595 600 605Arg Glu Phe Phe Lys Trp Ala Gly Asp Leu Gly Ala Asp Glu Glu Ser 610 615 620Ile Arg Asn Leu Phe Asp Phe Thr Pro Lys Tyr Arg Ala Thr His Glu625 630 635 640Asp Gln Lys Phe Lys Lys Val Lys Glu Cys Ser Ser Glu Leu Lys Tyr 645 650 655Ser Met Glu Leu Asp Glu Lys Asp Glu Asp Lys Phe Phe Ser Gln Glu 660 665 670Lys Tyr Trp Gly Arg Lys Phe His Thr Pro Ser Asn Ser Tyr Thr Ala 675 680 685Gln Arg Val Lys Met Lys Tyr Gly Ala Trp Tyr Leu Lys Pro

Lys Leu 690 695 700Trp Lys Lys Leu Arg Ser Asp Glu Pro Leu Ile Asp Pro Lys Leu Leu705 710 715 720Leu Lys Lys Pro Asp Glu Pro Asp Val Leu Asp Asp Leu Tyr Gly Pro 725 730 735Ile Ala Phe Lys Asp Phe Ile Leu Ser Lys Gly Tyr Glu Met Pro Gly 740 745 750Ile Ile Gln Arg Leu Phe Ala Arg Arg Gly Trp Thr Tyr Asp Ser Val 755 760 765Lys Thr Pro Ile Gln Arg Ala Met Ile Phe Tyr Lys Tyr Lys Glu Ile 770 775 780Val Glu Ala Ser Glu Glu Asp785 79028823PRTHomo sapiens 28Met Lys Arg His Arg Pro Val Ser Ser Ser Asp Ser Ser Asp Glu Ser1 5 10 15Pro Ser Thr Ser Phe Thr Ser Gly Ser Met Tyr Arg Ile Lys Ser Lys 20 25 30Ile Pro Asn Glu His Lys Lys Pro Ala Glu Val Phe Arg Lys Asp Leu 35 40 45Ile Ser Ala Met Lys Leu Pro Asp Ser His His Ile Asn Pro Asp Ser 50 55 60Tyr Tyr Leu Phe Ala Asp Thr Trp Lys Glu Glu Trp Glu Lys Gly Val65 70 75 80Gln Val Pro Ala Ser Pro Asp Thr Val Pro Gln Pro Ser Leu Arg Ile 85 90 95Ile Ala Glu Lys Val Lys Asp Val Leu Phe Ile Arg Pro Arg Lys Tyr 100 105 110Ile His Cys Ser Ser Pro Asp Thr Thr Glu Pro Gly Tyr Ile Asn Ile 115 120 125Met Glu Leu Ala Ala Ser Val Cys Arg Tyr Asp Leu Asp Asp Met Asp 130 135 140Ile Phe Trp Leu Gln Glu Leu Asn Glu Asp Leu Ala Glu Met Gly Cys145 150 155 160Gly Pro Val Asp Glu Asn Leu Met Glu Lys Thr Val Glu Val Leu Glu 165 170 175Arg His Cys His Glu Asn Met Asn His Ala Ile Glu Thr Glu Glu Gly 180 185 190Leu Gly Ile Glu Tyr Asp Glu Asp Val Ile Cys Asp Val Cys Arg Ser 195 200 205Pro Asp Ser Glu Glu Gly Asn Asp Met Val Phe Cys Asp Lys Cys Asn 210 215 220Val Cys Val His Gln Ala Cys Tyr Gly Ile Leu Lys Val Pro Glu Gly225 230 235 240Ser Trp Leu Cys Arg Ser Cys Val Leu Gly Ile Tyr Pro Gln Cys Val 245 250 255Leu Cys Pro Lys Lys Gly Gly Ala Leu Lys Thr Thr Lys Thr Gly Thr 260 265 270Lys Trp Ala His Val Ser Cys Ala Leu Trp Ile Pro Glu Val Ser Ile 275 280 285Ala Cys Pro Glu Arg Met Glu Pro Ile Thr Lys Ile Ser His Ile Pro 290 295 300Pro Ser Arg Trp Ala Leu Val Cys Asn Leu Cys Lys Leu Lys Thr Gly305 310 315 320Ala Cys Ile Gln Cys Ser Ile Lys Ser Cys Ile Thr Ala Phe His Val 325 330 335Thr Cys Ala Phe Glu His Gly Leu Glu Met Lys Thr Ile Leu Asp Glu 340 345 350Gly Asp Glu Val Lys Phe Lys Ser Tyr Cys Leu Lys His Ser Gln Asn 355 360 365Arg Gln Lys Leu Gly Glu Ala Glu Tyr Pro His His Arg Ala Lys Glu 370 375 380Gln Ser Gln Ala Lys Ser Glu Lys Thr Ser Leu Arg Ala Gln Lys Leu385 390 395 400Arg Glu Leu Glu Glu Glu Phe Tyr Ser Leu Val Arg Val Glu Asp Val 405 410 415Ala Ala Glu Leu Gly Met Pro Thr Leu Ala Val Asp Phe Ile Tyr Asn 420 425 430Tyr Trp Lys Leu Lys Arg Lys Ser Asn Phe Asn Lys Pro Leu Phe Pro 435 440 445Pro Lys Glu Asp Glu Glu Asn Gly Leu Val Gln Pro Lys Glu Glu Ser 450 455 460Ile His Thr Arg Met Arg Met Phe Met His Leu Arg Gln Asp Leu Glu465 470 475 480Arg Val Arg Asn Leu Cys Tyr Met Ile Ser Arg Arg Glu Lys Leu Lys 485 490 495Leu Ser His Asn Lys Ile Gln Glu Gln Ile Phe Gly Leu Gln Val Gln 500 505 510Leu Leu Asn Gln Glu Ile Asp Ala Gly Leu Pro Leu Thr Asn Ala Leu 515 520 525Glu Asn Ser Leu Phe Tyr Pro Pro Pro Arg Ile Thr Leu Lys Leu Lys 530 535 540Met Pro Lys Ser Thr Pro Glu Asp His Arg Asn Ser Ser Thr Glu Thr545 550 555 560Asp Gln Gln Pro His Ser Pro Asp Ser Ser Ser Ser Val His Ser Ile 565 570 575Arg Asn Met Gln Val Pro Gln Glu Ser Leu Glu Met Arg Thr Lys Ser 580 585 590Tyr Pro Arg Tyr Pro Leu Glu Ser Lys Asn Asn Arg Leu Leu Ala Ser 595 600 605Leu Ser His Ser Arg Ser Glu Ala Lys Glu Ser Ser Pro Ala Trp Arg 610 615 620Thr Pro Ser Ser Glu Cys Tyr His Gly Gln Ser Leu Gly Lys Pro Leu625 630 635 640Val Leu Gln Ala Ala Leu His Gly Gln Ser Ser Ile Gly Asn Gly Lys 645 650 655Ser Gln Pro Asn Ser Lys Phe Ala Lys Ser Asn Gly Leu Glu Gly Ser 660 665 670Trp Ser Gly Asn Val Thr Gln Lys Asp Ser Ser Ser Glu Met Phe Cys 675 680 685Asp Gln Glu Pro Val Phe Ser Pro His Leu Val Ser Gln Gly Ser Phe 690 695 700Arg Lys Ser Thr Val Glu His Phe Ser Arg Ser Phe Lys Glu Thr Thr705 710 715 720Asn Arg Trp Val Lys Asn Thr Glu Asp Leu Gln Cys Tyr Val Lys Pro 725 730 735Thr Lys Asn Met Ser Pro Lys Glu Gln Phe Trp Gly Arg Gln Val Leu 740 745 750Arg Arg Ser Ala Gly Arg Ala Pro Tyr Gln Glu Asn Asp Gly Tyr Cys 755 760 765Pro Asp Leu Glu Leu Ser Asp Ser Glu Ala Glu Ser Asp Gly Asn Lys 770 775 780Glu Lys Val Arg Val Arg Lys Asp Ser Ser Asp Arg Glu Asn Pro Pro785 790 795 800His Asp Ser Arg Arg Asp Cys His Gly Lys Ser Lys Thr His Pro Leu 805 810 815Ser His Ser Ser Met Gln Arg 82029518PRTHomo sapiens 29Met Ala Val Ala Leu Gly Cys Ala Ile Gln Ala Ser Leu Asn Gln Gly1 5 10 15Ser Val Phe Gln Glu Tyr Asp Thr Asp Cys Glu Val Phe Arg Gln Arg 20 25 30Phe Arg Gln Phe Gln Tyr Arg Glu Ala Ala Gly Pro His Glu Ala Phe 35 40 45Asn Lys Leu Trp Glu Leu Cys Cys Gln Trp Leu Lys Pro Lys Met Arg 50 55 60Ser Lys Glu Gln Ile Leu Glu Leu Leu Val Leu Glu Gln Phe Leu Thr65 70 75 80Ile Leu Pro Thr Glu Ile Glu Thr Trp Val Arg Glu His Cys Pro Glu 85 90 95Asn Arg Glu Arg Val Val Ser Leu Ile Glu Asp Leu Gln Arg Glu Leu 100 105 110Glu Ile Pro Glu Gln Gln Val Asp Met His Asp Met Leu Leu Glu Glu 115 120 125Leu Ala Pro Val Gly Thr Ala His Ile Pro Pro Thr Met His Leu Glu 130 135 140Ser Pro Ala Leu Gln Val Met Gly Pro Ala Gln Glu Ala Pro Val Ala145 150 155 160Glu Ala Trp Ile Pro Gln Ala Gly Pro Pro Glu Leu Asn Tyr Gly Ala 165 170 175Thr Gly Glu Cys Gln Asn Phe Leu Asp Pro Gly Tyr Pro Leu Pro Lys 180 185 190Leu Asp Met Asn Phe Ser Leu Glu Asn Arg Glu Glu Pro Trp Val Lys 195 200 205Glu Leu Gln Asp Ser Lys Glu Met Lys Gln Leu Leu Asp Ser Lys Ile 210 215 220Gly Phe Glu Ile Gly Ile Glu Asn Glu Glu Asp Thr Ser Lys Gln Lys225 230 235 240Lys Met Glu Thr Met Tyr Pro Phe Ile Val Thr Leu Glu Gly Asn Ala 245 250 255Leu Gln Gly Pro Ile Leu Gln Lys Asp Tyr Val Gln Leu Glu Asn Gln 260 265 270Trp Glu Thr Pro Pro Glu Asp Leu Gln Thr Asp Leu Ala Lys Leu Val 275 280 285Asp Gln Gln Asn Pro Thr Leu Gly Glu Thr Pro Glu Asn Ser Asn Leu 290 295 300Glu Glu Pro Leu Asn Pro Lys Pro His Lys Lys Lys Ser Pro Gly Glu305 310 315 320Lys Pro His Arg Cys Pro Gln Cys Gly Lys Cys Phe Ala Arg Lys Ser 325 330 335Gln Leu Thr Gly His Gln Arg Ile His Ser Gly Glu Glu Pro His Lys 340 345 350Cys Pro Glu Cys Gly Lys Arg Phe Leu Arg Ser Ser Asp Leu Tyr Arg 355 360 365His Gln Arg Leu His Thr Gly Glu Arg Pro Tyr Glu Cys Thr Val Cys 370 375 380Lys Lys Arg Phe Thr Arg Arg Ser His Leu Ile Gly His Gln Arg Thr385 390 395 400His Ser Glu Glu Glu Thr Tyr Lys Cys Leu Glu Cys Gly Lys Ser Phe 405 410 415Cys His Gly Ser Ser Leu Lys Arg His Leu Lys Thr His Thr Gly Glu 420 425 430Lys Pro His Arg Cys His Asn Cys Gly Lys Ser Phe Ser Arg Leu Thr 435 440 445Ala Leu Thr Leu His Gln Arg Thr His Thr Glu Glu Arg Pro Phe Lys 450 455 460Cys Asn Tyr Cys Gly Lys Ser Phe Arg Gln Arg Pro Ser Leu Val Ile465 470 475 480His Leu Arg Ile His Thr Gly Glu Lys Pro Tyr Lys Cys Thr His Cys 485 490 495Ser Lys Ser Phe Arg Gln Arg Ala Gly Leu Ile Met His Gln Val Thr 500 505 510His Phe Arg Gly Leu Ile 51530434PRTHomo sapiens 30Met Val Gln Asp Gly Thr Phe Lys Thr Arg Asp Ser Thr Trp Thr Cys1 5 10 15Glu Ser Thr Arg Met Ala Ala Ala Pro Pro Ser Tyr Cys Phe Val Ala 20 25 30Phe Pro Pro Arg Ala Lys Asp Gly Leu Val Val Phe Gly Lys Asn Ser 35 40 45Ala Arg Pro Arg Asp Glu Val Gln Glu Val Val Tyr Phe Ser Ala Ala 50 55 60Asp His Glu Pro Glu Ser Lys Val Glu Cys Thr Tyr Ile Ser Ile Asp65 70 75 80Gln Val Pro Arg Thr Tyr Ala Ile Met Ile Ser Arg Pro Ala Trp Leu 85 90 95Trp Gly Ala Glu Met Gly Ala Asn Glu His Gly Val Cys Ile Ala Asn 100 105 110Glu Ala Ile Asn Thr Arg Glu Pro Ala Ala Glu Ile Glu Ala Leu Leu 115 120 125Gly Met Asp Leu Val Arg Leu Gly Leu Glu Arg Gly Glu Thr Ala Lys 130 135 140Glu Ala Leu Asp Val Ile Val Ser Leu Leu Glu Glu His Gly Gln Gly145 150 155 160Gly Asn Tyr Phe Glu Asp Ala Asn Ser Cys His Ser Phe Gln Ser Ala 165 170 175Tyr Leu Ile Val Asp Arg Asp Glu Ala Trp Val Leu Glu Thr Ile Gly 180 185 190Lys Tyr Trp Ala Ala Glu Lys Val Thr Glu Gly Val Arg Cys Ile Cys 195 200 205Ser Gln Leu Ser Leu Thr Thr Lys Met Asp Ala Glu His Pro Glu Leu 210 215 220Arg Ser Tyr Ala Gln Ser Gln Gly Trp Trp Thr Gly Glu Gly Glu Phe225 230 235 240Asn Phe Ser Glu Val Phe Ser Pro Val Glu Asp His Leu Asp Cys Gly 245 250 255Ala Gly Lys Asp Ser Leu Glu Lys Gln Glu Glu Ser Ile Thr Val Gln 260 265 270Thr Met Met Asn Thr Leu Arg Asp Lys Ala Ser Gly Val Cys Ile Asp 275 280 285Ser Glu Phe Phe Leu Thr Thr Ala Ser Gly Val Ser Val Leu Pro Gln 290 295 300Asn Arg Ser Ser Pro Cys Ile His Tyr Phe Thr Gly Thr Pro Asp Pro305 310 315 320Ser Arg Ser Ile Phe Lys Pro Phe Ile Phe Val Asp Asp Val Lys Leu 325 330 335Val Pro Lys Thr Gln Ser Pro Cys Phe Gly Asp Asp Asp Pro Ala Lys 340 345 350Lys Glu Pro Arg Phe Gln Glu Lys Pro Asp Arg Arg His Glu Leu Tyr 355 360 365Lys Ala His Glu Trp Ala Arg Ala Ile Ile Glu Ser Asp Gln Glu Gln 370 375 380Gly Arg Lys Leu Arg Ser Thr Met Leu Glu Leu Glu Lys Gln Gly Leu385 390 395 400Glu Ala Met Glu Glu Ile Leu Thr Ser Ser Glu Pro Leu Asp Pro Ala 405 410 415Glu Val Gly Asp Leu Phe Tyr Asp Cys Val Asp Thr Glu Ile Lys Phe 420 425 430Phe Lys3129DNAArtificial SequenceACSS3 31gggataagat tgctatcatc tatgacagt 293229DNAArtificial SequenceACSS3 32gaaggctcta caatgagaat gtatgctat 293330DNAArtificial SequenceACSS3 33ttcagtcaga tgctcagact taaatagatt 303422DNAArtificial SequenceACSS3 34acagtcatgt gactgggctt tt 223529DNAArtificial SequenceACSS3 35ctctagatat aaatgcaaca gaggagcaa 293625DNAArtificial SequenceACSS3 36ccattgacaa tggcagataa agctg 253728DNAArtificial SequenceADAM21 37gggctttcga ggagtattaa aaataagt 283824DNAArtificial SequenceADAM21 38tgctacttcc ttctctgtta agcc 243930DNAArtificial SequenceADAM21 39gtatttcttg ttgtcaacat agtggattcc 304022DNAArtificial SequenceADAM21 40atgctgtagc tgggaaagac tg 224125DNAArtificial SequenceADAM21 41cttaaaccag ggatcatgtc tgcat 254222DNAArtificial SequenceADAM21 42gtcttgttca cactgctgta cg 224326DNAArtificial SequenceADAM21 43gatgtctttt gtgggagagt tcaatg 264422DNAArtificial SequenceADAM21 44ggccacacac agtaccatct tt 224525DNAArtificial SequenceAFF2 45tcaccaggat aatacccatc cttca 254622DNAArtificial SequenceAFF2 46agtctgcatc ttgtttggct ga 224719DNAArtificial SequenceAFF2 47tcggagagca gctctgagt 194820DNAArtificial SequenceAFF2 48ctgtgggaca ggcagatcat 204925DNAArtificial SequenceAFF2 49ggctttgaag cataagttgt caaca 255022DNAArtificial SequenceAFF2 50gggtcatgaa gctccacact tt 225124DNAArtificial SequenceAFF2 51gccaaatcca aggaaatctg tggt 245227DNAArtificial SequenceAFF2 52agaggttttt caggttctca tgatctc 275322DNAArtificial SequenceALG13 53tccggatacc tgcataagca ag 225426DNAArtificial SequenceALG13 54catccattga tgcctcattc aaagac 265528DNAArtificial SequenceALG13 55gaagactaag gattgtgagt ttgtagca 285630DNAArtificial SequenceALG13 56tcctgttgat atttctttac cttttctgct 305725DNAArtificial SequenceALG13 57tctttgttag tgattgcctc accat 255822DNAArtificial SequenceALG13 58agtctctccc acatcaagag ca 225927DNAArtificial SequenceBAP1 59gtaggagaga agaagactga gagcact 276023DNAArtificial SequenceBAP1 60gtggaggctg agattgcaaa cta 236123DNAArtificial SequenceBAP1 61ttccaatcaa gaacttggca cct 236219DNAArtificial SequenceBAP1 62gtcgtggaag ccacggaca 196322DNAArtificial SequenceBAP1 63gccgtgtctg tactctcatt gc 226422DNAArtificial SequenceBAP1 64ccatcaacgt cttggctgag aa 226523DNAArtificial SequenceBAP1 65aacctggtag ccttagaaag ctg 236623DNAArtificial SequenceBAP1 66ttgtcccagg aggaagaaga cct 236724DNAArtificial SequenceBAP1 67gggacttggc ataattgtga ttgt 246822DNAArtificial SequenceBAP1 68atcccacagc cctcccaaca aa 226922DNAArtificial SequenceBAP1 69gcttcaccac tagcttgggt tt 227023DNAArtificial SequenceBAP1 70gggagactgt gagcttttct tgg 237121DNAArtificial SequenceBAP1

71ggacttgttg ctggctgact t 217222DNAArtificial SequenceBAP1 72gggtctaccc tttctcctct ga 227327DNAArtificial SequenceBAP1 73gtatgttcac gaatcagaga caaatgc 277422DNAArtificial SequenceBAP1 74cgaccgcagg atcaagtatg ag 227522DNAArtificial SequenceBAP1 75cagcctggcc tcatacttga tc 227624DNAArtificial SequenceBAP1 76caggatatct gcctcaacct gatg 247722DNAArtificial SequenceBAP1 77catggtgcct accatggtca at 227822DNAArtificial SequenceBAP1 78cctgagaagc agaatggcct ta 227920DNAArtificial SequenceBAP1 79cgcactgcac taaggccatt 208022DNAArtificial SequenceBAP1 80gccaaggccc ataatagcca tg 228122DNAArtificial SequenceBAP1 81cacacacctg gcatggctat ta 228224DNAArtificial SequenceBAP1 82cccatagtcc tacctgagga gaaa 248322DNAArtificial SequenceBAP1 83ctgaaaccct tggtgaagtc ct 228423DNAArtificial SequenceBAP1 84ttggtttcac agctgatacc caa 238522DNAArtificial SequenceBAP1 85atcccaccct ccaaacaaag ca 228626DNAArtificial SequenceBAP1 86cccagccctg tatatggatt tatctt 268723DNAArtificial SequenceBAP1 87gctgctgctt tctgtgagat ttt 238822DNAArtificial SequenceBAP1 88gggtgcaagt ggaggagatc ta 228922DNAArtificial SequenceBAP1 89ccctgacatt tgctctgaag gt 229022DNAArtificial SequenceBAP1 90tcggtaagag ccttttctcc ct 229123DNAArtificial SequenceBAP1 91tcttaccgaa atcttccacg agc 239222DNAArtificial SequenceBAP1 92aagatgaata agggctggct gg 229328DNAArtificial SequenceBAP1 93cttactgaac actgtaacac tggaaaga 289428DNAArtificial SequenceBAP1 94gtgggaacag agctaatatt ctcaagag 289522DNAArtificial SequenceBRWD3 95agaggatcct cagtggacac aa 229624DNAArtificial SequenceBRWD3 96ctagaggagc taccagagcc aaac 249726DNAArtificial SequenceBRWD3 97attgttttta catgccattg ccagaa 269830DNAArtificial SequenceBRWD3 98ttgatgttag gctgaacatg aaaacttttt 309930DNAArtificial SequenceCOL4A5 99attaaattct ctgtggcaaa caataaggac 3010022DNAArtificial SequenceCOL4A5 100tgggaaacca cgatcacctt tt 2210120DNAArtificial SequenceCOL4A5 101cagctggaca gaagggtgaa 2010229DNAArtificial SequenceCOL4A5 102gtgtgtggta gcttagtaag aaagaagat 2910326DNAArtificial SequenceCOL4A5 103caaaaactgg tttctctcac accaat 2610422DNAArtificial SequenceCOL4A5 104tggaggacca gcatctcctt ta 2210525DNAArtificial SequenceCOL4A5 105cctcattctt ttcctgtagg tccaa 2510625DNAArtificial SequenceCOL4A5 106tctctcagac tcaaagactt tccct 2510724DNAArtificial SequenceCOL4A5 107ccttgaaagg ctgtttgcta ttgt 2410829DNAArtificial SequenceCOL4A5 108tcttgaagca aagttgcaaa cattattga 2910923DNAArtificial SequenceCOL4A5 109ctgcttggaa gagtttcgtt cag 2311023DNAArtificial SequenceCOL4A5 110ccctagcatc tctgaaggaa gct 2311122DNAArtificial SequenceCPEB1 111cccacctgat ctcgacagaa ga 2211222DNAArtificial SequenceCPEB1 112tggccaataa tgtgcccttc tt 2211323DNAArtificial SequenceCPEB1 113cacaagaaaa tccagtgcct caa 2311422DNAArtificial SequenceCPEB1 114aagtctgtcc gatccttgct tc 2211522DNAArtificial SequenceCPEB1 115ctaactgagg gtgctggaaa ct 2211623DNAArtificial SequenceCPEB1 116gctgttggct gcaaagaaaa cta 2311723DNAArtificial SequenceERBB2 117gtttgagtga aggcattcat ggt 2311826DNAArtificial SequenceERBB2 118gatctcttcc agagtctcaa acactt 2611922DNAArtificial SequenceERBB2 119caagagggtg gttcccagaa tt 2212022DNAArtificial SequenceERBB2 120gagtgaaggg caatgaaggg ta 2212122DNAArtificial SequenceERBB2 121ggctggctcc gatgtatttg at 2212222DNAArtificial SequenceERBB2 122caacgtagcc atcagtctca ga 2212329DNAArtificial SequenceHSP90AA1 123attacatagt ataaggctta cccagacca 2912423DNAArtificial SequenceHSP90AA1 124cgacaagtct gtgaaggatc tgg 2312531DNAArtificial SequenceHSP90AA1 125cctgataact ttcaaaattt tgctttgttg c 3112623DNAArtificial SequenceHSP90AA1 126gtccttggaa tgactcagtg cat 2312732DNAArtificial SequenceHSP90AA1 127cagacagaaa ttcactctgc aattacataa aa 3212820DNAArtificial SequenceHSP90AA1 128caggtgaacc tatgggtcgt 2012923DNAArtificial SequenceHSP90AA1 129cccaagaagt tcacactgaa acc 2313020DNAArtificial SequenceHSP90AA1 130tgagacgttc gcctttcagg 2013119DNAArtificial SequenceIRAK1 131cgcctaggct ctcgtcact 1913219DNAArtificial SequenceIRAK1 132cccgcaggag aactcctac 1913320DNAArtificial SequenceIRAK1 133ccaggtgtca ggagtgcttt 2013421DNAArtificial SequenceIRAK1 134acaggtttcg tcacccaaac a 2113522DNAArtificial SequenceKDM5C 135tccgtaccct ctttggctct ag 2213625DNAArtificial SequenceKDM5C 136tgtctttctg cctgtctgta atcac 2513720DNAArtificial SequenceKDM5C 137ccagaagtgt gcggatcctc 2013820DNAArtificial SequenceKDM5C 138agttgactgg ccctgtgttg 2013923DNAArtificial SequenceKDM5C 139cccacacaca cagatagagg ttg 2314021DNAArtificial SequenceKDM5C 140ctgtcctggg tatggcagat c 2114121DNAArtificial SequenceKDM5C 141ccatctgtgt cgaagctcct t 2114221DNAArtificial SequenceKDM5C 142gttctctgcc catgtgcaga t 2114322DNAArtificial SequenceKDM5C 143ctcttctggg tctccactca ac 2214422DNAArtificial SequenceKDM5C 144cctagccctg ctgtggataa ag 2214523DNAArtificial SequenceKDM5C 145caggttgttc atctggtcca gaa 2314625DNAArtificial SequenceKDM5C 146agtcttagca tagacatgga gggaa 2514722DNAArtificial SequenceKDM5C 147gcctcactca ggcagttctt ta 2214826DNAArtificial SequenceKDM5C 148cctctgcctc tattcaatac tgccta 2614922DNAArtificial SequenceKDM5C 149ctactggagc acttgcagag at 2215022DNAArtificial SequenceKDM5C 150gatgatgagc gccagtgtat ca 2215122DNAArtificial SequenceKDM5C 151cccgaacttc caccagaata gg 2215223DNAArtificial SequenceKDM5C 152ccagagaagc tagacctgaa cct 2315323DNAArtificial SequenceKDM5C 153ccatcttgca gataagctcc tca 2315423DNAArtificial SequenceKDM5C 154gaagcaggag ggttgtagag aag 2315522DNAArtificial SequenceKDM5C 155gcaaagttgt agccttggtt ga 2215627DNAArtificial SequenceKDM5C 156caggaaaatc tctatctcaa cagccat 2715722DNAArtificial SequenceKDM5C 157gaggtcaggc tggctatcaa at 2215822DNAArtificial SequenceKDM5C 158cctgcatgac caaggtgtga tt 2215922DNAArtificial SequenceKDM5C 159ggagcccaca ctgacttgat tc 2216022DNAArtificial SequenceKDM5C 160gtactgtgcc acatcaatgc ag 2216125DNAArtificial SequenceKDM5C 161atgccagaga tatctgcatt gatgt 2516230DNAArtificial SequenceKDM5C 162gttccctagg ctaaagaaaa tgacttaaga 3016329DNAArtificial SequenceKDM5C 163agatactaaa tgatttgcct aagctcaca 2916426DNAArtificial SequenceKDM5C 164tagcattgag gaagatgtga ctgttg 2616525DNAArtificial SequenceKDM5C 165gggaatgctt attgaaggga caaga 2516623DNAArtificial SequenceKDM5C 166cctaagacct tcctggagag caa 2316722DNAArtificial SequenceKDM5C 167gtagcctcat ggtcatcttg gt 2216826DNAArtificial SequenceKDM5C 168ccatttttct ctctcccaga taagga 2616922DNAArtificial SequenceKDM5C 169tccctccacc tcaaagctct aa 2217030DNAArtificial SequenceKDM5C 170taatgaggag aaggacaagg aatacaaacc 3017123DNAArtificial SequenceKDM5C 171gcaaggagcc aatatttttg cct 2317223DNAArtificial SequenceKDM5C 172ctacaggcct actccctcac ata 2317322DNAArtificial SequenceKDM5C 173accaccagct cctagtcttc tc 2217424DNAArtificial SequenceKDM5C 174cttttggtga cttccggtct taca 2417519DNAArtificial SequenceKDM5C 175cgatgggcct gattttcgc 1917619DNAArtificial SequenceKDM5C 176gcgccatgag tccttaagg 1917722DNAArtificial SequenceKDM6A 177ccaagcaaga attcatgcac gt 2217828DNAArtificial SequenceKDM6A 178agactcatag tctgtgttca ctttgaac 2817923DNAArtificial SequenceKDM6A 179cactgttcat tgggttcagg cta 2318030DNAArtificial SequenceKDM6A 180aaaaaggaac agtcctattg gatataatcc 3018122DNAArtificial SequenceLRP12 181acctcgggta ctctgagttg ag 2218224DNAArtificial SequenceLRP12 182aagtttgttt tccgtggagt ctga 2418324DNAArtificial SequenceLRP12 183tccacggaaa acaaacttct gtga 2418422DNAArtificial SequenceLRP12 184ttcctatggc aggcagatca ag 2218524DNAArtificial SequenceNCOA6 185ctgggaagtt tgttaggatc cgaa 2418622DNAArtificial SequenceNCOA6 186caaggagagc ttgaatgtgc ct 2218722DNAArtificial SequenceNCOA6 187cccaaaatgg cctgcagata tg 2218822DNAArtificial SequenceNCOA6 188ggccatggga tgtctttcaa tg 2218923DNAArtificial SequenceNCOA6 189ctccactgaa aggtgcattg aaa 2319026DNAArtificial SequenceNCOA6 190ggtgatcctg ctactacagc aaataa 2619125DNAArtificial SequenceNCOA6 191gcagggctca aatgatcaaa taagc 2519223DNAArtificial SequenceNCOA6 192ttggctcaga accgaagcca aga 2319330DNAArtificial SequenceNHS 193tccaagtaaa tgaaaatttg tttgccattt 3019422DNAArtificial SequenceNHS 194gggatacccg agatggtttt cc 2219526DNAArtificial SequenceNHS 195acagcaaccc tctttaaaag atggaa 2619630DNAArtificial SequenceNHS 196tctcctactg tgttctgctt attatgagta 3019722DNAArtificial SequenceNHS 197accgtcatcc actgcatgtt tt 2219828DNAArtificial SequenceNHS 198cttaacttct tcagacttgt tgatggac 2819923DNAArtificial SequenceRGAG1 199gaatgatgtc atccatgcca caa 2320022DNAArtificial SequenceRGAG1 200agtgtgcaca tgtctccaga ag 2220122DNAArtificial SequenceRGAG1 201gtccacattg caaaccagtg tt 2220222DNAArtificial SequenceRGAG1 202catgggcatc gatccagaaa ct 2220326DNAArtificial SequenceRGAG1 203ccacatcatt tatgagagcc tcagtt 2620422DNAArtificial SequenceRGAG1 204tgtggtgtgg acattgttcc ag 2220521DNAArtificial SequenceSCAF1 205ccatgtgtcc cattggcttc t 2120620DNAArtificial SequenceSCAF1 206gggttcgtga gcaaaggagg 2020719DNAArtificial SequenceSCAF1 207cgctttagct ccgcctctc 1920819DNAArtificial SequenceSCAF1 208actagcgacc caactccgc 1920921DNAArtificial SequenceSCAF1 209gggacctcca ctccaaactc t 2121024DNAArtificial SequenceSCAF1 210ctcaccagga taaaggcaga agga 2421119DNAArtificial SequenceSCAF1 211atggtccgcc agacagaga 1921222DNAArtificial SequenceSCAF1 212gtgcttcaag ggagccaaga gt 2221321DNAArtificial SequenceSCAF1 213gcacttgagt ctagctgtca g 2121422DNAArtificial SequenceSCAF1 214ccgccatacc tttatcattg gg 2221522DNAArtificial SequenceSH3TC1 215ccacaggctt cactcatcac tg 2221622DNAArtificial SequenceSH3TC1 216caacgctcac cttcttggat ga 2221722DNAArtificial SequenceSH3TC1 217cagtgaccac ctccatcctt tt 2221821DNAArtificial SequenceSH3TC1 218ggcggtgaag agtctgtttc c 2121927DNAArtificial SequenceSH3TC1 219tctgtctgtc aaatcaagga atggaaa 2722022DNAArtificial SequenceSH3TC1 220cctggcatcc tcctcagaaa ag 2222130DNAArtificial SequenceTBC1D8B 221atgagataca tcagcatgct aatagaagtg 3022226DNAArtificial SequenceTBC1D8B 222catatcagtc atgtgttctg tcagct 2622329DNAArtificial SequenceTBC1D8B 223agcagacatg gtttttaaaa tcttccaaa 2922429DNAArtificial SequenceTBC1D8B 224cagtcaatct gatactgttc caaatatgg 2922529DNAArtificial SequenceTBC1D8B 225ccatatttgg aacagtatca gattgactg 2922628DNAArtificial SequenceTBC1D8B 226taccaattgc agaggagaat tctttgaa 2822725DNAArtificial SequenceTBC1D8B 227tggaaggaaa ctacatagcc ctaca 2522823DNAArtificial SequenceTBC1D8B 228caacagcgat gcaagaatct gtt 2322922DNAArtificial SequenceTET2 229taactgcagt gggcctgaaa at 2223022DNAArtificial SequenceTET2 230agttcaccat gtgtgtgttc ca 2223124DNAArtificial SequenceTET2 231cctgtgatgc tgatgatgct gata 2423223DNAArtificial SequenceTET2 232aattcttcac cagacgctag ctt 2323324DNAArtificial SequenceTET2 233ggaaaaagca ctctgaatgg tgga 2423423DNAArtificial SequenceTET2 234gcctttcaga aagcatcgga gaa 2323522DNAArtificial SequenceTET2 235aactgccagc agttgatgag aa 2223625DNAArtificial SequenceTET2 236ttacgtttta gatgggattc cgctt 2523722DNAArtificial SequenceTET2 237caccaagcgg aatcccatct aa

2223823DNAArtificial SequenceTET2 238agctgtgttg ttttctgggt gta 2323923DNAArtificial SequenceTET2 239aaacacaacc atcccagagt tca 2324029DNAArtificial SequenceTET2 240ccatgaaaac attcttccac tttagtctg 2924122DNAArtificial SequenceTET2 241gggtcactgc atgtttggac tt 2224224DNAArtificial SequenceTET2 242gcagtgtgag aacagactca acag 2424324DNAArtificial SequenceTET2 243aagtctctga cgtggatgag tttg 2424422DNAArtificial SequenceTET2 244gaaagctttt cagctgcagc tt 2224527DNAArtificial SequenceTET2 245aggtttggaa atagccagag ttttaca 2724622DNAArtificial SequenceTET2 246atctagaggt ggctcccatg aa 2224730DNAArtificial SequenceTEX13A 247tcgagatata catgcttcgg ttctattttg 3024823DNAArtificial SequenceTEX13A 248ctcatcagca aagacctcca gta 2324922DNAArtificial SequenceTEX13A 249gggttcgtgg ttccagagaa at 2225022DNAArtificial SequenceTEX13A 250cctccatgga gaccacagag aa 2225121DNAArtificial SequenceTEX13A 251tctctccagc ttctctgtgg t 2125222DNAArtificial SequenceTEX13A 252ctgctggagg aaaaggagca ga 2225322DNAArtificial SequenceULK3 253gcctgaagag agtgtccctt ct 2225424DNAArtificial SequenceULK3 254ccaagaaaag tctgaacaag gcat 2425523DNAArtificial SequenceWNK3 255gctgaagaga aggaggagac tga 2325630DNAArtificial SequenceWNK3 256cctggcttct tcagtcaata aggtaaataa 3025727DNAArtificial SequenceWNK3 257gaaacttgct ggtaatgtcc tactagt 2725822DNAArtificial SequenceWNK3 258ggcaggagct gcatcagtta ta 2225923DNAArtificial SequenceWNK3 259gtgctgctgt ggttttcttt gta 2326024DNAArtificial SequenceWNK3 260gggattctca gtgcaagtct atgg 2426125DNAArtificial SequenceARSF 261gtgcatgacg acaagcctaa tattg 2526222DNAArtificial SequenceARSF 262acgactgacg aacgtatgac tg 2226320DNAArtificial SequenceCFP 263gctgtagcag tgccggatat 2026424DNAArtificial SequenceCFP 264acatgaagtc catcagctgt caag 2426522DNAArtificial SequenceCFP 265ccgggatttc ttgacagctg at 2226623DNAArtificial SequenceCFP 266tgattccctg ctttggtcca atc 2326721DNAArtificial SequenceCFP 267cccactctga ggacctctgt a 2126820DNAArtificial SequenceCFP 268gaatgggcag tgctctggaa 2026920DNAArtificial SequenceCFP 269ggcaaaggca gtgttgagac 2027019DNAArtificial SequenceCFP 270gtgtccaggc ccaccacat 1927121DNAArtificial SequenceFAM47A 271actggatctc cgacgagtga t 2127223DNAArtificial SequenceFAM47A 272gagactggag tgtcccatct aag 2327325DNAArtificial SequencePHF16(JADE3) 273acgccattgc catgaaaata tgaac 2527423DNAArtificial SequencePHF16(JADE3) 274tccactctca ctaacctgat gca 2327524DNAArtificial SequencePHF16(JADE3) 275ccattctagg agtgaagcaa agga 2427622DNAArtificial SequencePHF16(JADE3) 276gccattggat ttggcaaact tg 2227722DNAArtificial SequenceZNF449 277ggagctgaac tatggtgcta ct 2227829DNAArtificial SequenceZNF449 278cattgagtaa ttggtgtttc taacccaac 2927928DNAArtificial SequenceSCRN1 279ttttgctggt aatttagtaa ggtgggaa 2828023DNAArtificial SequenceSCRN1 280cctggaagcc atggaagaaa tcc 2328124DNAArtificial SequenceSCRN1 281agggtatgag aaggagaatc gtga 2428222DNAArtificial SequenceSCRN1 282gaactcagga gttacgctca ga 22

Claims

1-12. (canceled)

13. A method of providing information required to verify a difference in therapeutic effect against kidney cancer according to the gender of a patient with kidney cancer, the method comprising: preparing a DNA test sample from a sample of a patient with kidney cancer whose gender is identified; identifying the presence or absence of a gender specific marker in a DNA test sample; treating the patient with kidney cancer, in which the gender-specific marker is identified, with any candidate material for treating kidney cancer or healing the patient with kidney cancer using any method; and choosing any candidate material for treating kidney cancer or any method of treating kidney cancer as a therapeutic candidate material or a therapeutic method, which is suitable for the gender group of patients with kidney cancer in which the gender-specific marker is identified, when the any candidate material or the any method is used to treat kidney cancer, wherein the gender specific marker is a mutation of a gene coding for ADAM21, wherein the mutation of a gene coding for ADAM21 is at least one mutation selected from the group consisting of N265Y, R408C, T589S, and I161V in the amino acid sequence set forth in SEQ ID NO: 2.

14. The method of claim 13, wherein the patient with kidney cancer is a female.

15. The method of claim 13, wherein the gender-specific marker further comprises a mutation of a gene coding for one selected from the group consisting of ALG13, BRWD3, CPEB1, ERBB2, HSP90AA1, IRAK1, KDM6A, LRP12, NCOA6, NHS, RGAG1, SCAF1, SH3TC1, TEX13A, ULK3, WNK3, ARSF, CFP, PHF16, ZNF449, and SCRN1.

16. The method of claim 15, wherein the mutation of the gene coding for ALG13 is at least one missense mutation selected from P925T and V456E, or a frameshift deletion (FS del) mutation `L195Pfs*23` in the amino acid sequence set forth in SEQ ID NO: 4; the mutation of the gene coding for BRWD3 is at least one missense mutation selected from G287A and I1747N in the amino acid sequence set forth in SEQ ID NO: 6; the mutation of the gene coding for CPEB1 is at least one missense mutation selected from S393R and G136V, or a splice mutation `X499_splice` (where C is substituted with A at position 83215272 on the chromosome) in the amino acid sequence set forth in SEQ ID NO: 8; the mutation of the gene coding for ERBB2 is at least one missense mutation selected from the group consisting of E1114G, 5649T, and V219I, or a frameshift insertion (FS ins) mutation `N388Qfs*14` in the amino acid sequence set forth in SEQ ID NO: 9; the mutation of the gene coding for HSP90AA1 is at least one missense mutation selected from the group consisting of D512N, H806R, I325T, and L167V in the amino acid sequence set forth in SEQ ID NO: 10; the mutation of the gene coding for IRAK1 is a nonsense mutation `Q280*`, or at least one missense mutation selected from V548M and Q584K in the amino acid sequence set forth in SEQ ID NO: 11; the mutation of the gene coding for KDM6A is a missense mutation `A3OV`, an FS mutation `A1246Pfs*19`, or an IF del mutation `V156del` in the amino acid sequence set forth in SEQ ID NO: 13; the mutation of the gene coding for LRP12 is at least one missense mutation selected from the group consisting of S622L, E639K, and V671I in the amino acid sequence set forth in SEQ ID NO: 14; the mutation of the gene coding for NCOA6 is at least one missense mutation selected from the group consisting of G164E, N877I, N864Y, and V1444A, or an FS ins mutation `H832Sfs*47` in the amino acid sequence set forth in SEQ ID NO: 15; the mutation of the gene coding for NHS is at least one missense mutation selected from the group consisting of C360R, P1107A, and D1069H in the amino acid sequence set forth in SEQ ID NO: 16; the mutation of the gene coding for RGAG1 is at least one missense mutation selected from the group consisting of A1015G, M858V, and G1053R in the amino acid sequence set forth in SEQ ID NO: 17; the mutation of the gene coding for SCAF1 is at least one FS ins mutation selected from the group consisting of A219Sfs*11, P211Tfs*19, P211Tfs*19, and A216Pfs*94, or an FS del mutation `A216Pfs*94` in the amino acid sequence set forth in SEQ ID NO: 18; the mutation of the gene coding for SH3TC1 is at least one missense mutation selected from A375V and L180F or an FS del mutation `R238Sfs*38` in the amino acid sequence set forth in SEQ ID NO: 19; the mutation of the gene coding for TEX13A is at leasint one missense mutation selected from R393S and Y257D, or a splice mutation `X199_splice` (where C at position 104464282 is deleted from the chromosome) in the amino acid sequence set forth in SEQ ID NO: 22; the mutation of the gene coding for ULK3 is an FS del mutation `Q81Sfs*41` and at least one missense mutation selected from D79H and L77V in the amino acid sequence set forth in SEQ ID NO: 23; the mutation of the gene coding for WNK3 is at least one nonsense mutation selected from S865* and Y589* and a missense mutation `E537G` in the amino acid sequence set forth in SEQ ID NO: 24; the mutation of the gene coding for ARSF is a missense mutation `I42F` in the amino acid sequence set forth in SEQ ID NO: 25; the mutation of the gene coding for CFP is at least one missense mutation selected from the group consisting of S27L, R359Q, and E135K, or an FS ins mutation `E323Gfs*34` in the amino acid sequence set forth in SEQ ID NO: 26; the mutation of the gene coding for PHF16 is at least one missense mutation selected from K656Q and R207W in the amino acid sequence set forth in SEQ ID NO: 28; the mutation of the gene coding for ZNF449 is a missense mutation `F1831` in the amino acid sequence set forth in SEQ ID NO: 29; and the mutation of the gene coding for SCRN1 is a missense mutation `D427Y` or an FS ins mutation `A257Cfs*34` in the amino acid sequence set forth in SEQ ID NO: 30.

17. A method of providing information required to diagnose prognosis of kidney cancer according to the gender of a patient with kidney cancer, the method comprising: preparing a DNA test sample from a sample of a patient with kidney cancer; identifying the presence or absence of a gender specific maker in a DNA test sample; and judging that the survival rate of the patient with kidney cancer is not good or the relapse rate of kidney cancer in the patient with kidney cancer is high when the gender-specific marker is identified; wherein the gender specific marker is a mutation of a gene coding for ADAM21, wherein the mutation of a gene coding for ADAM21 is at least one mutation selected from the group consisting of N265Y, R408C, T589S, and I161V in the amino acid sequence set forth in SEQ ID NO: 2.

18. The method of claim 17, wherein the gender-specific marker further comprises a mutation of a gene coding for one selected from the group consisting of ALG13, ARSF, KDM6A, PHF16, ZNF449, and SCRN1; wherein the mutation of the gene coding for ALG13 is at least one missense mutation selected from P925T and V456E, or a frameshift deletion (FS del) mutation `L195Pfs*23` in the amino acid sequence set forth in SEQ ID NO: 4; the mutation of the gene coding for ARSF is a missense mutation `I42F` in the amino acid sequence set forth in SEQ ID NO: 25; the mutation of the gene coding for KDM6A is a missense mutation `A30V`, an FS mutation `A1246Pfs*19`, or an IF del mutation `V156del` in the amino acid sequence set forth in SEQ ID NO: 13; the mutation of the gene coding for PHF16 is at least one missense mutation selected from K656Q and R207W in the amino acid sequence set forth in SEQ ID NO: 28; the mutation of the gene coding for ZNF449 is a missense mutation `F1831` in the amino acid sequence set forth in SEQ ID NO: 29; and the mutation of the gene coding for SCRN1 is a missense mutation `D427Y` or an FS ins mutation `A257Cfs*34` in the amino acid sequence set forth in SEQ ID NO: 30.