CN111344394A - 分离对p53癌症-特异性突变具有抗原特异性的t细胞的方法 - Google Patents

分离对p53癌症-特异性突变具有抗原特异性的t细胞的方法 Download PDF

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CN111344394A
CN111344394A CN201880063656.4A CN201880063656A CN111344394A CN 111344394 A CN111344394 A CN 111344394A CN 201880063656 A CN201880063656 A CN 201880063656A CN 111344394 A CN111344394 A CN 111344394A
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德鲁·C·丹尼格尔
史蒂文·A·罗森伯格
帕里萨·马勒克扎德
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Abstract

本申请公开了分离对由癌症‑特异性p53突变编码的突变的p53氨基酸序列具有抗原特异性的T细胞的方法，该方法包括：诱导患者的自体APC呈递突变的p53氨基酸序列；共培养患者的自体T细胞与呈递突变的p53氨基酸序列的自体APC；和选择自体T细胞。还公开了制备细胞群的相关方法、细胞群、药物组合物以及治疗或预防癌症的方法。

Description

分离对P53癌症-特异性突变具有抗原特异性的T细胞的方法
相关申请的交叉引用
本专利申请要求2017年9月29日提交的美国临时专利申请No.62/565,464的权益，其通过引用整体并入本文。
关于联邦政府资助的研究和开发的声明
本发明是由美国国立卫生研究院国家癌症研究所(National Institutes ofHealth,National Cancer Institute)在政府支持下完成的，项目号为ZIABC010984。政府拥有本发明的某些权利。
通过引用并入以电子方式提交的材料
通过引用整体并入本文的是与此同时提交并且标识如下的计算机可读核苷酸/氨基酸序列表：日期为2018年9月14日的一个名为"740175_ST25.txt"的687,616字节ASCII(文本)文件。
发明背景
过继细胞疗法(ACT)在某些癌症患者中可以产生积极的临床响应。尽管如此，成功使用ACT广泛治疗癌症和其他疾病的障碍仍然存在。例如，特异性识别癌症抗原的T细胞可能难以从患者鉴定和/或分离。因此，需要获得癌症-反应性T细胞的改进方法。
发明简述
本发明的一个实施方案提供了分离T细胞的方法，所述T细胞对由癌症-特异性p53突变所编码的突变的p53氨基酸序列具有抗原特异性，所述方法包括：诱导患者的自体抗原呈递细胞(APC)呈递至少一种突变的p53氨基酸序列；共培养患者的自体T细胞与呈递突变的p53氨基酸序列的自体APC；以及选择(a)与呈递突变的p53氨基酸序列的自体APC共培养和(b)对在由患者表达的主要组织相容性复合物(MHC)分子的情况下呈递的经突变的p53氨基酸序列具有抗原特异性的自体T细胞，以提供对由癌症-特异性p53突变所编码的突变的p53氨基酸序列具有抗原特异性的经分离的T细胞。
本发明的另一个实施方案提供了分离对由癌症-特异性p53突变所编码的突变的p53氨基酸序列具有抗原特异性的T细胞受体(TCR)或其抗原结合部分的方法，所述方法包括：根据本文所述的任一方法分离对由癌症-特异性p53突变所编码的突变的p53氨基酸序列具有抗原特异性的T细胞；和从选定的自体T细胞分离编码TCR或其抗原结合部分的核苷酸序列，其中TCR或其抗原结合部分对由癌症-特异性p53突变所编码的突变的p53氨基酸序列具有抗原特异性。
本发明的又一个实施方案提供了制备表达TCR或其抗原结合部分的细胞群的方法，所述TCR或其抗原结合部分对由癌症-特异性p53突变所编码的突变的p53氨基酸序列具有抗原特异性，所述方法包括：根据本文所述的任一方法分离TCR或其抗原结合部分，以及将编码分离的TCR或其抗原结合部分的核苷酸序列引入至外周血单核细胞(PBMC)中以获得表达TCR或其抗原结合部分的细胞。
本发明的另一个实施方案提供了制备对由癌症-特异性p53突变所编码的突变的p53氨基酸序列具有抗原特异性的T细胞群的方法，所述方法包括：根据本文所述的任一方法分离T细胞，和扩大选定的自体T细胞的数量以获得对由癌症-特异性p53突变所编码的突变的p53氨基酸序列具有抗原特异性的T细胞群。
本发明的另外实施方案提供了相关的细胞群、药物组合物以及治疗或预防癌症的方法。
若干附图视图的简述
图1是显示在共培养效应细胞和靶细胞之后测量的每2x104个效应细胞的IFN-γ阳性点的数量的图。效应细胞是来自患者4141的TIL片段F12，输液袋TIL(Rx1)，来自患者4196的p53-R175H-特异性TCR-转导的细胞或模拟物转导的T细胞。靶细胞是HLA-A*02:01APC(对于患者4141是自体的)，其(1)用由无关(IRR；左侧斜线灰条)、WT p53(p53wt-TMG；右侧斜线灰条)或经突变的p53(p53-mut-TMG；灰条)序列组成的TMG电穿孔或(2)用肽媒介物(DMSO；左侧斜线黑条)或由WT p53-R175序列(LP-p53-wt-R175；右侧斜线黑条)或经突变的p53-R175H(LP-p53-mut-R175H；黑条)序列组成的经纯化的(>95％，通过HPLC)25个氨基酸的肽脉冲。仅T细胞(无靶标；空条)是阴性对照，并且佛波醇12-肉豆蔻酸酯13-乙酸酯(PMA)和离子霉素(Iono)是阳性对照(格条)。
图2是显示在来自患者4130的TIL片段(F14、F20或F24)与自体APC共培养之后检测的4-1BB+细胞的百分比(CD4+百分比)的图，所述自体APC(1)用由无关(IRR；空条)、WT p53(p53-WT；水平黑条)或突变的p53(p53-MUT；灰条)序列组成的TMG电穿孔或(2)用肽媒介物(DMSO；左侧斜线黑条)或由WT p53-R273序列(LP-p53-R273-WT；左侧斜线灰条)或突变的p53-R273H(LP-p53-R273H-MUT；黑条)序列组成的经纯化的(>95％，通过HPLC)25个氨基酸的肽脉冲。
图3是显示在共培养来自患者4259的TIL片段(F1-6、F9、F13-23，n＝18)与自体APC之后测量的每2x104个效应细胞的IFN-γ阳性点的数量的图，所述自体APC用由无关(IRR；空条)、WT p53(p53-WT；灰条)或经突变的p53(p53-MUT；黑条)序列组成的TMG电穿孔。
图4是显示在共培养来自患者4259的TIL片段(F1-F6、F9、F13-F23，n＝18)与自体APC之后检测的4-1BB+细胞的百分比(CD4+百分比)的图，所述自体APC用由无关(IRR；空条)、WT p53(p53-WT；灰条)或突变的p53(p53-MUT；黑条)序列组成的TMG电穿孔。
图5是显示在共培养来自患者4259的TIL片段(F1-F6、F9、F13-F23，n＝18)与自体APC之后检测的4-1BB+细胞的百分比(CD8+百分比)的图，所述自体APC用由无关(IRR；空条)、WT p53(p53-WT；灰条)或突变的p53(p53-MUT；黑条)序列组成的TMG电穿孔。
图6是显示在共培养来自患者4259的TIL片段(F1-F6、F9、F13-23，n＝18)与自体APC之后测量的每2x104个效应细胞的IFN-γ阳性点的数量的图，所述自体APC用肽媒介物(DMSO；空条)或由WT p53-Y220序列(LP-p53-Y220-WT；灰条)或突变的p53-Y220C(LP-p53-Y220C-MUT；黑条)序列组成的经纯化的(>95％，通过HPLC)25个氨基酸的肽脉冲。
图7是显示在共培养来自患者4259的TIL片段(F1-F6、F9、F13-F23，n＝18)与自体APC之后检测的4-1BB+细胞的百分比(CD4+百分比)的图，所述自体APC用肽媒介物(DMSO；空条)或由WT p53-Y220序列(LP-p53-Y220-WT；灰条)或突变的p53-Y220C(LP-p53-Y220C-MUT；黑条)序列组成的经纯化的(>95％，通过HPLC)25个氨基酸的肽脉冲。
图8是显示在共培养来自患者4259的TIL片段(F1-F6、F9、F13-F23，n＝18)与自体APC之后检测的4-1BB+细胞的百分比(CD8+百分比)的图，所述自体APC用肽媒介物(DMSO；空条)或由WT p53-Y220序列(LP-p53-Y220-WT；灰条)或突变的p53-Y220C(LP-p53-Y220C-MUT；黑条)序列组成的经纯化的(>95％，通过HPLC)25个氨基酸的肽脉冲。
图9是显示在共培养来自患者4127的TIL与同种异体的(DRB3*01:01:01或DRB3*02:02:01)APC之后测量的每2x104个效应细胞的IFN-γ阳性点的数量的图，所述同种异体的(DRB3*01:01:01或DRB3*02:02:01)APC(1)用由无关(IRR；左侧斜线空条)WT p53(p53-WT；左侧斜线灰条)或突变的p53(p53-MUT；灰条)序列组成的TMG电穿孔或(2)用肽媒介物(DMSO；右侧斜线空条)或由WT p53-G245序列(LP-p53-wt-G245；右侧斜线灰条)或突变的p53-G245S(LP-p53-mut-G245S；黑条)序列组成的经纯化的(>95％，通过HPLC)25个氨基酸的肽脉冲。
图10是显示在共培养表达4127-TCR1的T细胞与同种异体的(DRB3*01:01:01或DRB3*02:02:01)APC之后测量的每2x104个效应细胞的IFN-γ阳性点的数量的图，所述同种异体的(DRB3*01:01:01或DRB3*02:02:01)APC(1)用由无关(IRR；左侧斜线空条)、WT p53(p53-WT；左侧斜线灰条)或经突变的p53(p53-MUT；灰条)序列组成的TMG电穿孔或(2)用肽媒介物(DMSO；右侧斜线空条)或由WT p53-G245序列(LP-p53-wt-G245；右侧斜线灰条)或经突变的p53-G245S(LP-p53-mut-G245S；黑条)序列组成的经纯化的(>95％，通过HPLC)25个氨基酸的肽脉冲。
图11是显示在共培养来自患者4273的TIL片段(F1-F24，n＝24)与自体APC之后测量的每2x104个效应细胞的IFN-γ-阳性点的数量的图，所述自体APC用由无关(IRR；空条)WT p53(p53-WT；灰条)或经突变的p53(p53-MUT；黑条)序列组成的TMG(TMG)电穿孔。
图12是显示在共培养患者4273TIL片段F1-F24(n＝24)与自体APC之后检测的4-1BB+(CD4+百分比)细胞的百分比的图，所述自体APC用由无关(IRR；空条)WT p53(p53-WT；灰条)或经突变的p53(p53-MUT；黑条)序列组成的TMG电穿孔。
图13是显示在共培养来自患者4273的TIL片段(F1-F24，n＝24)与自体APC之后测量的每2x104个效应细胞的IFN-γ-阳性点的数量的图，所述自体APC用肽媒介物(DMSO；空条)或由WT p53-R248序列(LP-p53-R248-WT；灰条)或经突变的p53-R248W(LP-p53-R248W-MUT；黑条)序列组成的经纯化的(>95％，通过HPLC)25-个氨基酸的肽脉冲。
图14是显示在共培养来自患者4273的TIL片段(F1-F24,n＝24)与自体APC之后检测的4-1BB+(CD4+百分比)细胞的百分比的图，所述自体APC用肽媒介物(DMSO；空条)或由WTp53-R248序列(LP-p53-R248-WT；灰条)或经突变的p53-R248W(LP-p53-R248W-MUT；黑条)序列组成的经纯化的(>95％，通过HPLC)25-个氨基酸的肽脉冲。
图15是显示在共培养来自患者4149的自体PBL(用4149-TCRa2b1或4149-TCRa2b2转座)与自体APC之后测量的每2x104个效应细胞的IFN-γ-阳性点的数量的图，所述自体APC(1)用由无关(IRR；右侧斜线黑条)、WT p53(p53-wt-TMG；左侧斜线黑条)或经突变的p53(p53-mut-TMG；灰条)序列组成的TMG电穿孔或(2)用肽媒介物(DMSO；空条)或由WT p53-Y220序列(LP-p53-Y220-WT；水平斜线黑条)或经突变的p53-Y220C(LP-p53-Y220C-MUT；黑条)序列组成的经纯化的(>95％，通过HPLC)25-个氨基酸的肽脉冲。佛波醇12-肉豆蔻酸酯13-乙酸酯(PMA)和离子霉素(Iono)是阳性对照(灰条)。
图16是显示在共培养来自患者4149的用TCR(4149-TCRa2b1或4149-TCRa2b2)转座的自体PBL与自体APC之后检测的4-1BB+(CD4+百分比)细胞的百分比的图，所述自体APC(1)用由无关(IRR；右侧斜线黑条)、WT p53(p53-wt-TMG；左侧斜线黑条)或经突变的p53(p53-mut-TMG；灰条)序列组成的TMG电穿孔或(2)用肽媒介物(DMSO；空条)或由WT p53-Y220序列(LP-p53-Y220-WT；水平斜线黑条)或经突变的p53-Y220C(LP-p53-Y220C-MUT；黑条)序列组成的经纯化的(>95％，通过HPLC)25-个氨基酸的肽脉冲。PMA和Iono是阳性对照(灰条)。
图17是显示在共培养来自患者4149的TIL与用表10的一种肽脉冲的自体DC之后检测的4-1BB+细胞的百分比(CD4+T细胞百分比)的图。
图18是显示在共培养4149-TCRa2b2转座的T细胞与同单独HLA等位基因+/-TMG共转染的Cos7细胞之后的IFN-γ分泌(pg/mL)的图。将未用TMG转染的细胞用p53Y220C 15-mer肽脉冲。经脉冲的靶细胞由阴影条表示。用TMG转染的靶细胞由无阴影条表示。
图19是显示在共培养来自患者4213的TIL片段(F2和F24)与自体APC之后检测的4-1BB+细胞的百分比(CD8+百分比)的图，所述自体APC用肽媒介物(DMSO；空条)或由经突变的p53-R248Q(LP-p53-R248Q-MUT；黑条)序列组成的经纯化的(>95％，通过HPLC)25-个氨基酸的肽脉冲。
图20是显示在共培养来自患者4213的CD4+T细胞与自体APC之后测量的每2x104个效应细胞的IFN-γ-阳性点的数量的图，所述自体APC用肽媒介物(DMSO；空条)或由突变的p53-R248Q(LP-p53-R248Q-MUT；黑条)序列组成的经纯化的(>95％，通过HPLC)25-个氨基酸的肽脉冲。IFN-γ的分泌由空条显示。4-1BB的表达由实心条显示。
图21是显示在共培养来自患者4268的TIL片段(F1-F24,n＝24)与自体APC之后测量的每2x104个效应细胞的IFN-γ-阳性点的数量的图，所述自体APC用由无关(IRR；空条)、WT p53(p53-WT；灰条)或经突变的p53(p53-MUT；黑条)序列组成的TMG电穿孔。
图22是显示在共培养来自患者4268的TIL片段(F1-F24，n＝24)与自体APC之后测量的每2x104个效应细胞的IFN-γ-阳性点的数量的图，所述自体APC用肽媒介物(DMSO；空条)或由WT p53-R248序列(LP-p53-R248-WT；灰条)或经突变的p53-R248Q(LP-p53-R248Q-MUT；黑条)序列组成的经纯化的(>95％，通过HPLC)25-个氨基酸的肽脉冲。
图23是显示在共培养来自患者4268的TIL片段(F1-F24,n＝24)与自体APC之后检测的4-1BB+细胞的百分比(CD4+百分比)的图，所述自体APC用肽媒介物(DMSO；空条)或由WTp53-R248序列(LP-p53-R248-WT；灰条)或经突变的p53-R248Q(LP-p53-R248Q-MUT；黑条)序列组成的经纯化的(>95％，通过HPLC)25-个氨基酸的肽脉冲。
图24是显示在共培养来自患者4268的TIL片段(F1-F24,n＝24)与自体APC之后检测的4-1BB+细胞的百分比(CD8+百分比)的图，所述自体APC用肽媒介物(DMSO；空条)或由WTp53-R248序列(LP-p53-R248-WT；灰条)或经突变的p53-R248Q(LP-p53-R248Q-MUT；黑条)序列组成的经纯化的(>95％，通过HPLC)25-个氨基酸的肽脉冲。
图25是显示在共培养来自患者4266的TIL片段(F1-F24，n＝24)与自体APC之后测量的每2x104个效应细胞的IFN-γ-阳性点的数量的图，所述自体APC用由无关(IRR；空条)、WT p53(p53-WT；灰条)或经突变的p53(p53-MUT；黑条)序列组成的TMG电穿孔。
图26是显示在共培养来自患者4266的TIL片段(F1-F24，n＝24)与自体APC之后检测的4-1BB+细胞的百分比(CD8+百分比)的图，所述自体APC用由无关(IRR；空条)、WT p53(p53-WT；灰条)或经突变的p53(p53-MUT；黑条)序列组成的TMG电穿孔。
图27是显示在共培养来自患者4266的TIL片段(F1-F24，n＝24)与自体APC之后测量的每2x104个效应细胞的IFN-γ-阳性点的数量的图，所述自体APC用肽媒介物(DMSO；空条)或由WT p53-R248序列(LP-p53-R248-WT；灰条)或经突变的p53-R248W(LP-p53-R248W-MUT；黑条)序列组成的经纯化的(>95％，通过HPLC)25-个氨基酸的肽脉冲。
图28是显示在共培养来自患者4266的TIL片段(F1-F24，n＝24)与自体APC之后检测的4-1BB+细胞的百分比(CD8+百分比)的图，所述自体APC用肽媒介物(DMSO；空条)或由WTp53-R248序列(LP-p53-R248-WT；灰条)或经突变的p53-R248W(LP-p53-R248W-MUT；黑条)序列组成的经纯化的(>95％，通过HPLC)25-个氨基酸的肽脉冲。
图29是显示在共培养来自患者4266的TIL与Cos7细胞之后检测的4-1BB+细胞的百分比(CD8+百分比)的图，所述Cos7细胞用来自患者4266的单独HLA等位基因共转染以及用无肽(空条)、DMSO(肽媒介物；灰条)、WT p53-R248肽(灰斜线条)或经突变的p53-R248W肽(黑条)脉冲。数据是平均值±SEM(n＝3)。
图30是显示在共培养表达模拟物(无TCR)、4266-TCR1、4266-TCR2、4266-TCR3或4266-TCR4的T细胞与自体APC之后检测的4-1BB+细胞的百分比(CD8+百分比)的图，所述自体APC用肽媒介物(DMSO；灰条)或由WT p53-R248序列(斜线灰条)或经突变的p53-R248W(黑条)序列组成的经纯化的(>95％，通过HPLC)25个氨基酸的肽脉冲。单独的培养基(空条)及PMA和离子霉素(格条)分别是阴性对照和阳性对照。
图31是显示在共培养表达模拟物(无TCR)或p53-R248W-特异性TCR(4266-TCR2、4266-TCR3或4266-TCR4)的T细胞与从由患者4266切除的异种移植的肿瘤碎片建立然后通过免疫受损小鼠(TC#4266)连续传代的肿瘤细胞(TC)系之后检测的4-1BB+细胞的百分比(CD8+百分比)的图。将TC#4266细胞不与任何物质孵育(黑条)、或将TC#4266细胞与W6/32泛-HLA I类特异性阻断抗体(右侧灰斜线条)、IVA12泛-HLA II类特异性阻断抗体(灰条)或突变的p53-R248W肽(左侧灰斜线条)孵育。单独的培养基(无TC；空条)及PMA和离子霉素(灰格条)分别是阴性对照和阳性对照。
图32显示了九种p53剪接变体的氨基酸序列的比对。SP|P04637|P53_HUMAN(SEQID NO:1)；SP|P04637-2|P53_HUMAN(SEQ ID NO:535)；SP|P04637-3|P53_HUMAN(SEQ IDNO:536)；SP|P04637-4|P53_HUMAN(SEQ ID NO:537)；SP|P04637-5|P53_HUMAN(SEQ ID NO:538)；SP|P04637-6|P53_HUMAN(SEQ ID NO:539)；SP|P04637-7|P53_HUMAN(SEQ ID NO:540)；SP|P04637-8|P53_HUMAN(SEQ ID NO:541)；和SP|P04637-9|P53_HUMAN(SEQ ID NO:542)。
图33是显示在共培养来自患者4273的TIL与自体APC之后检测的4-1BB+细胞的百分比(CD8+百分比)的图，所述自体APC用编码无关突变(灰条)、WT p53序列(灰斜线条)或突变的p53序列(包括p53-R248W(黑条))的TMG转染。单独的培养基(空条)及PMA和离子霉素(格条)分别是阴性对照和阳性对照。
图34是显示在共培养来自患者4273的TIL与自体APC之后检测的4-1BB+细胞的百分比(CD4+百分比)的图，所述自体APC用对应于来自p53-R248W新表位的WT(空环)或突变的(实心方块)的25个氨基酸的肽脉冲。DMSO是肽媒介物。
图35是显示在共培养来自患者4273的TIL与自体APC之后检测的4-1BB+细胞的百分比(CD4+百分比)的图，所述自体APC用来自p53-R248W新表位的重叠14个氨基酸的15个氨基酸的肽(氨基酸取代呈粗体)脉冲。DMSO是肽媒介物，单独的培养基(仅T细胞)及PMA和离子霉素是对照。25个氨基酸的肽(wt p53-R248和经突变的p53-R248W)是15个氨基酸的肽的另外对照。肽是：
Figure BDA0002430898550000091
(SEQ ID NO:592)；
Figure BDA0002430898550000092
(SEQ ID NO:593)；
Figure BDA0002430898550000093
(SEQ ID NO:594)；
Figure BDA0002430898550000094
(SEQ ID NO:595)；
Figure BDA0002430898550000095
(SEQ ID NO:596)；
Figure BDA0002430898550000096
(SEQ ID NO:597)；
Figure BDA00024308985500000910
(SEQ IDNO:598)；
Figure BDA0002430898550000097
(SEQ ID NO:599)；
Figure BDA0002430898550000098
(SEQ IDNO:600)；
Figure BDA0002430898550000099
(SEQ ID NO:601)；和MNWRPILTIITLEDS(SEQ ID NO:602)。
图36是显示来自患者4273的TIL与Cos7细胞共培养之后分泌的IFN-γ(pg/mL)的浓度的图，所述Cos7细胞用来自患者4273的HLA等位基因以及分别在有或无p53-R248W新抗原的情况下的WT(空条)或突变的(黑条)TP53 TMG共转染。
图37是显示在表达模拟物(无TCR)或4273-TCR1a2的T细胞与自体APC的共培养之后测量的每2x104个效应细胞的IFN-γ-点的数量的图，所述自体APC用肽媒介物(DMSO；灰条)或由WT p53-R248序列(斜线灰条)或经突变的p53-R248W(黑条)序列组成的经纯化的(>95％，通过HPLC)25个氨基酸的肽脉冲。单独的培养基(空条)及PMA和离子霉素(格条)分别是阴性对照和阳性对照。
图38是显示在共培养来自患者4252的TIL片段F1、F3、F7或F19与自体APC(不成熟的DC)之后检测的4-1BB+细胞的百分比(CD4+百分比)的图，所述自体APC(不成熟的DC)(1)用由无关(IRR；左侧斜线灰条)、WT p53(p53wt-TMG；右侧斜线灰条)或经突变的p53(p53-mut-TMG；灰条)序列组成的TMG电穿孔，或(2)用肽媒介物(DMSO；左侧斜线黑条)或由WTp53-R175序列(LP-p53-wt-R175；右侧斜线黑条)或经突变的p53-R175H(LP-p53-mut-R175H；黑条)序列组成的经纯化的(>95％，通过HPLC)25个氨基酸的肽脉冲。仅T细胞(无靶标；空条)是阴性对照并且PMA和Iono是阳性对照(格条)。数据是平均值±SEM(n＝3)。学生t检验按系在指定组之间进行。*p<0.05，**p<0.01，***p<0.001。
图39是显示在共培养来自患者4270的TIL片段F13或F16与自体APC(不成熟的DC)之后测量的每2x104个细胞的IFN-γ点的数量的图，所述自体APC(不成熟的DC)(1)用由无关(IRR；左侧斜线灰条)、WT p53(p53wt-TMG；右侧斜线灰条)或突变的p53(p53-mut-TMG；灰条)序列组成的TMG电穿孔，或(2)用肽媒介物(DMSO；左侧斜线黑条)或由WT p53-R282序列(LP-p53-wt-R282；右侧斜线黑条)或突变的p53-R282W(LP-p53-mut-R282W；黑条)序列组成的经纯化的(>95％，通过HPLC)25个氨基酸的肽脉冲。仅T细胞(无靶标；空条)是阴性对照并且PMA和Iono是阳性对照(格条)。数据是平均值±SEM(n＝3)。
图40是显示在共培养来自患者4285的TIL片段(F1-F24，n＝18)与自体APC之后测量的每2x104个细胞的IFN-γ点的数量的图，所述自体APC用由无关(IRR；空条)、WT p53(p53-WT；灰条)或突变的p53(p53-MUT；黑条)序列组成的TMG电穿孔。
图41是显示在共培养来自患者4285的TIL片段(F1-F24，n＝18)与自体APC之后测量的每2x104个细胞的IFN-γ点的数量的图，所述自体APC用肽媒介物(DMSO；空条)或由WTp53-R175序列(LP-p53-R175-WT；灰条)或经突变的p53-R175H(LP-p53-R175H-MUT；黑条)序列组成的经纯化的(>95％，通过HPLC)25个氨基酸的肽脉冲。
图42是显示在共培养来自患者4285的TIL片段(F1-F24，n＝18)与自体APC之后检测的4-1BB+细胞的百分比(CD4+百分比)的图，所述自体APC用由无关(IRR；空条)WT p53(p53-WT；灰条)或经突变的p53(p53-MUT；黑条)序列组成的TMG电穿孔。
图43是显示在共培养来自患者4285的TIL片段(F1-F24，n＝18)与自体APC之后检测的4-1BB+细胞的百分比(CD4+百分比)的图，所述自体APC用肽媒介物(DMSO；空条)或由WTp53-R175序列(LP-p53-R175-WT；灰条)或经突变的p53-R175H(LP-p53-R175H-MUT；黑条)序列组成的经纯化的(>95％，通过HPLC)25个氨基酸的肽脉冲。
图44是显示在经测序的141种上皮肿瘤的位于指定p53密码子处的每种错义p53突变的总突变频率(％)的图。
图45是显示在共培养来自患者4141的TIL(片段培养物12)与自体APC之后测量的4-1BB阳性细胞的百分比(CD8+百分比)(右侧y-轴；黑条)和IFN-γ(每2x104个细胞的点)(左侧y-轴；斜线条)的图，所述自体APC用编码无关突变(TMG-IRR)、WT p53序列(TP53-wt-TMG)或包含R175H的经突变的p53序列(TP53-mut-TMG)的TMG转染。单独的培养基及PMA和离子霉素分别是阴性对照和阳性对照。
图46是显示在共培养来自患者4141的TIL(片段培养物12)与Cos7细胞之后测量的每2x104个效应细胞的IFN-γ-阳性点的数量的图，所述Cos7细胞用指定的HLA等位基因以及无额外基因(仅HLA；空条)、WT TP53 TMG(灰斜线条)或突变的(黑条)TP53 TMG(含p53-R175H序列)共转染。
图47是显示在共培养表达模拟物(无TCR)或4141-TCR1a2的T细胞与T2肿瘤细胞(表达HLA-A*02:01)之后测量的IFN-γ(pg/mL)的浓度的图。将T2细胞用肽媒介物(DMSO；灰条)或由WT p53-R175肽(斜线灰条)或经突变的p53-R175H肽(黑条)组成的经纯化的(>95％，通过HPLC)肽脉冲。单独的培养基(空条)及PMA和离子霉素(格条)分别是阴性对照和阳性对照。数据是平均值±SEM(n＝3)。
图48是显示在共培养表达4141-TCR1a2的T细胞与Saos2细胞(p53-NULL和HLA-A*02:01+)之后对于一种指定标志物的表达呈阳性的细胞的百分比的图，所述细胞未经操纵(无阴影条)，或被使得过表达全长p53-R175H蛋白(阴影条)。数据是平均值±SEM(n＝3)。对两个细胞系之间的每种细胞因子进行了学生双尾t检验，以进行统计分析(***p<0.001)。
图49是显示在共培养TIL(来自患者4259的片段培养物6)与自体APC之后检测的CD4+4-1BB阳性细胞的百分比的图，所述自体APC(1)用由无关(TMG-IRR)、WT p53(TMG-p53-WT)或经突变的p53(TMG-p53-MUT)序列组成的TMG电穿孔，或(2)用肽媒介物(DMSO)或由WTp53-Y220序列(LP-p53-Y220-WT)或经突变的p53-Y220C(LP-p53-Y220C-MUT)序列组成的经纯化的(>95％，通过HPLC)25-个氨基酸的肽脉冲。
图50是显示共培养来自患者4259的TIL片段培养物(no.6)与自体APC之后检测的CD4+4-1BB阳性细胞的百分比的图，所述自体APC用降低浓度的25-个氨基酸的肽(对应于WTp53序列(空心环)或突变的p53-Y220C(实心方块))在37℃下脉冲2小时。
图51是显示在共培养来自患者4259的TIL与用DMSO、WT p53-Y220肽或经突变的p53-Y220C肽脉冲的自体APC之后检测的CD4+4-1BB阳性细胞的百分比的图。
图52是显示在共培养来自患者4259的TIL片段培养物no.6与Cos7细胞之后检测的4-1BB阳性细胞的百分比(CD4+百分比)的图，所述Cos7细胞用来自患者4259的指定的HLA等位基因共转染并用DMSO(空条)或p53-Y220C肽(实心条)脉冲。
图53是显示在共培养TC#4259靶细胞(内源性表达p53-Y220C和HLA-DRB1*04:01:01)与表达模拟物(无TCR；空条)或p53-Y220C-特异性TCR(4259-F6-TCR；黑条)的效应T细胞(105)之后检测的4-1BB+细胞的百分比的图。将TC#4259细胞不与任何物质孵育、或将TC#4259细胞与W6/32泛-HLA I类特异性阻断抗体、IVA12泛-HLA II类特异性阻断抗体或经突变的p53-Y220C肽孵育。单独的培养基(无TC)及PMA和离子霉素分别是阴性对照和阳性对照。数据是平均值±SEM(n＝3)。在如指定进行统计分析的组之间进行学生双尾t检验(**p<0.01和***p<0.001)。
图54是显示在共培养TIL片段培养物4285-F6、4285-F9和4285-F10与Cos7细胞之后检测的4-1BB+细胞的百分比(CD4+百分比)的图，所述Cos7细胞用指定HLA等位基因转染并用DMSO(肽媒介物；灰和黑斜线条)或突变的p53-R175H肽(灰、格子和黑条)脉冲。
图55是显示在共培养用4285-TCR1转座的T细胞与自体APC之后检测的4-1BB+细胞的百分比(CD4+百分比)的图，所述自体APC用降低浓度的25-个或15-个氨基酸的肽(对应于WT(空心环和方块)或经突变的(实心环和方块)p53-R175H序列)脉冲。
发明详述
肿瘤蛋白P53(也称为“TP53”或“p53”)通过例如调节细胞分裂而作为肿瘤遏制物。p53蛋白位于细胞核中，在那里其直接结合至DNA。当DNA受损时，p53蛋白参与确定DNA是否会被修复或受损的细胞是否会发生凋亡。如果DNA可以被修复，则p53激活其他基因以恢复损伤。如果DNA无法被修复，则p53蛋白阻止细胞分裂并向其发出进行凋亡的信号。通过阻止具有突变或受损DNA的细胞分裂，p53有助于预防肿瘤发展。野生型(WT)全长p53包含SEQ IDNO:1的氨基酸序列。
p53蛋白中的突变可降低或消除p53蛋白的肿瘤遏制功能。可替代地或另外地，p53突变可以是通过以显性负性方式干扰野生型p53的功能获得性突变。经突变的p53蛋白可以在多种人类癌症中的任一种中表达，诸如例如，胆管癌、黑素瘤、结肠癌、直肠癌、卵巢癌、子宫内膜癌、非小细胞肺癌(NSCLC)、成胶质细胞瘤、子宫颈癌、头颈癌、乳房癌、胰腺癌或膀胱癌。
本发明的一个实施方案提供了分离对由癌症-特异性p53突变编码的p53突变的氨基酸序列具有抗原特异性的T细胞的方法。p53的突变在本文中通过参考全长氨基酸酸序列WT p53(SEQ ID NO:1)来定义。因此，p53的突变在本文中通过参考在特定位置存在的氨基酸残基，然后是位置编号，然后是在所讨论的特定突变中取代此残基的氨基酸来描述。例如，当位置如由SEQ ID NO:1所定义时，术语“R175”是指存在于SEQ ID NO:1的位置175处的精氨酸，“R175H”表示存在于SEQ ID NO:1的位置175处的精氨酸被组氨酸替代，而“G245S”表示存在于SEQ ID NO:1的位置245处的甘氨酸已经被丝氨酸替代。P53具有九种已知的剪接变体。本文所述的p53突变在所有九种p53剪接变体中是保守的。图32中显示了9种p53剪接变体的比对。因此，通过本发明的方法分离的T细胞可对由九种p53剪接变体中任一种编码的本文所述的任何经突变的p53氨基酸序列具有抗原特异性。当位置如SEQ ID NO:1所定义时，则p53的特定剪接变体的氨基酸序列的实际位置是相对于SEQ ID NO:1的相应位置来定义的，并且如由SEQ ID NO:1定义的位置可与特定剪接变体中的实际位置不同。因此，例如，突变是指对应于SEQ ID NO:1的393个氨基酸的序列的指定位置的p53的特定剪接变体的氨基酸序列中的氨基酸残基的替代，要理解剪接变体中的实际位置可有所不同。
本发明的实施方案可以提供许多优势中的任一个或多个。经突变的p53由癌细胞表达并且不在正常的非癌性细胞中表达。不受特定理论或机制的束缚，认为通过本发明方法分离的T细胞有利地靶向癌细胞的破坏，同时最小化或消除了正常的非癌性细胞的破坏，从而例如通过最小化或消除来减少毒性。此外，通过本发明方法分离的T细胞可以有利地成功治疗或预防对其他类型的治疗(诸如例如化疗、手术或辐照)无响应的突变的p53阳性癌症。另外，通过本发明的方法分离的T细胞可以提供对突变的p53的高度亲合的识别，其可以提供识别未经操纵的肿瘤细胞(如，未用干扰素(IFN)-γ处理、用编码经突变的p53和适用的HLA分子中的一种或两种的载体转染、用带有p53突变的p53肽脉冲或其组合的肿瘤细胞)的能力。在所有肿瘤中，大约有一半的肿瘤具有在p53中的突变，其中大约一半是错义突变并且约30％的错义突变发生在以下“热点”残基处：R175H、Y220C、G245D、G245S、R248L、R248Q、R248W、R249S、R273C、R273L、R273H和R282W。此外，p53中的相同“热点”突变(如，R175H、Y220C、G245D、G245S、R248L、R248Q、R248W、R249S、R273H、R273C、R273L或R282W)在无关人群的肿瘤中频繁发生(累计约占p53错义突变的30％)。因此，通过本发明方法分离的T细胞可增加可能适合用免疫疗法治疗的患者的数量。
与分离癌症突变-反应性T细胞的传统方法相比，本发明的方法可以更快、更专注且更有特异性。此类传统方法包括在将患者自体T细胞与呈递包含由一种或多种经鉴定的基因编码的癌症-特异性突变的肽的患者自体抗原呈递细胞共培养之前，鉴定由患者表达的含有癌症-特异性突变(如新抗原)的一种或多种基因，如在例如US 2017/0218042和US2017/0224800中所述(下文称“传统筛选方法”)。利用本发明的方法，可以在筛选患者之前生产、储存和验证包含p53突变的肽和串联微基因(TMG)，使得一旦在患者的肿瘤中鉴定出p53突变，就可不依赖于患者肿瘤中其他突变的知识，对患者的T细胞进行测试。这可以减少执行该方法所需的时间，这在评价终末期患者时特别有利。例如，本发明方法的持续时间可以比传统的筛选方法短如约3至约6周。在不存在其他竞争性突变的情况下，本发明的方法还可提供p53突变响应的高度专注的研究。不受特定理论或机制的束缚，认为患者突变-来源的TMG中的肽汇集物或竞争性肽汇集物(突变存在于除p53以外的蛋白中)可干扰突变的p53肽，并可能掩盖T细胞响应。因为本发明的方法只关注一种基因p53中的突变，所以与传统的筛选方法相比，本发明的方法可以提供提高的速度和效率来尝试鉴定p53突变-特异性T细胞和TCR，其涉及解析肽汇集物或TMG中的新抗原以确定哪种新抗原产生了T细胞响应。本发明的方法可以有利地产生可用于自体或同种异体疗法的T细胞和/或TCR。通过关注p53突变，可能会鉴定低频响应，其可在传统筛选方法的高通量中被稀释，并且可允许鉴定否则会因筛选数十至数百种新抗原的复杂性而丢失的T细胞和TCR。本发明的方法可以不依赖于患者是否患有相应的突变或甚至肿瘤的知识而用于测试患者中的T细胞响应。本发明的方法可用于筛选具有确定的HLA单倍型和预测的p53突变结合的患者，但不限于筛选该类型的群组。
癌症-特异性p53突变可以是编码经突变的p53氨基酸序列(也称为“非沉默突变”)并且在癌细胞中表达但在正常非癌性细胞中不表达的p53基因中的任何突变。癌症-特异性p53突变的非限制性实例包括错义、无义、插入、缺失、重复、移码和重复扩增突变。在一个优选的实施方案中，p53突变是错义突变。
在本发明的一个实施方案中，经突变的p53氨基酸序列包括在SEQ ID NO:1的位置175、220、245、248、249、273或282处具有突变的人p53氨基酸序列。p53突变可以是任何错义突变。因此，SEQ ID NO:1的位置175、220、245、248、249、273或282处的突变可以是SEQ IDNO:1的位置175、220、245、248、249、273或282处存在的天然(WT)氨基酸残基的取代，其中在所讨论的特定位置处存在除天然(WT)氨基酸残基以外的任何氨基酸残基。在本发明的一个实施方案中，经突变的p53氨基酸序列包括具有以下人p53突变中的一种的人p53氨基酸序列：R175H、Y220C、G245D、G245S、R248L、R248Q、R248W、R249S、R273H、R273C、R273L或R282W。例如，突变的p53氨基酸序列可包括选自由SEQ ID NO:2-13组成的组的突变的p53氨基酸序列。
该方法可以包括诱导患者的自体抗原呈递细胞(APC)呈递至少一种经突变的p53氨基酸序列。APC可包括在其细胞表面上呈递与主要组织相容性复合物(MHC)分子缔合的蛋白质的肽片段的任何细胞。APC可包括例如巨噬细胞、DC、朗格汉斯细胞、B-淋巴细胞和T-细胞中的任一种或多种。优选地，APC是DC。通过使用来自患者的自体APC，本发明的方法可以有利地鉴定对由癌症-特异性p53突变编码的经突变的p53氨基酸序列具有抗原特异性的T细胞，所述经突变的p53氨基酸序列在由患者表达的MHC分子的情况下呈递。MHC分子可以是患者表达的任何MHC分子，包括但不限于MHC I类、MHC II类、HLA-A、HLA-B、HLA-C、HLA-DM、HLA-DO、HLA-DP、HLA-DQ和HLA-DR分子。本发明的方法可以有利地鉴定在由患者表达的任何MHC分子的情况下呈递的经突变的p53氨基酸序列，而不使用例如表位预测算法来鉴定MHC分子或经突变的p53氨基酸序列，其仅可用于选定的少量MHC I类等位基因并且可受限于有限可用的选择p53突变-反应性T细胞的试剂(如，不完整组的MHC四聚体)。因此，在本发明的一个实施方案中，本发明的方法有利地诱导APC在由患者表达的任何MHC分子的情况下呈递经突变的p53氨基酸序列，并且不限于任何特定的MHC分子。优选地，自体APC是抗原-阴性的自体APC。
可以使用本领域已知的任何适合的方法来进行诱导患者的自体APC呈递至少一种突变的p53氨基酸序列。在本发明的一个实施方案中，诱导患者的自体APC呈递至少一种经突变的p53氨基酸序列包括用包含不超过一种突变的p53氨基酸序列的肽或者肽汇集物脉冲自体APC，肽汇集物中的每种肽均包含不同的突变的p53氨基酸序列。在这方面，可以以一定方式将自体APC与包含经突变的p53氨基酸序列的肽或肽汇集物一起培养，以使APC内化一种或多种肽并在细胞膜上展示结合至MHC分子的一种或多种突变的p53氨基酸序列。脉冲APC的方法在本领域中是已知的，并且在如Solheim(Ed.),Antigen Processing andPresentation Protocols(Methods in Molecular Biology),Human Press,(2010)中进行了描述。用于脉冲APC的一种或多种肽可包含由癌症-特异性p53突变编码的一种或多种经突变的p53氨基酸。一种或多种肽还可在一个或多个经突变的氨基酸的每个羧基侧和氨基侧上包含来自由p53基因编码的内源p53蛋白的任何适合数量的连续氨基酸。侧接突变的每一侧的来自内源性p53蛋白的连续氨基酸的数量不受限制，并且可以是例如约4、约5、约6、约7、约8、约9、约10、约11、约12、约13、约14、约15、约16、约17、约18、约19、约20，或由前述值的任两个限定的范围。优选地，一种或多种肽在经突变的氨基酸的每一侧上包含来自内源p53蛋白的约12个连续氨基酸。在一个实施方案中，肽或肽汇集物包含SEQ ID NO:2-13的经突变的p53肽中的一种或多种(表1)。
在本发明的一个实施方案中，诱导患者的自体APC呈递经突变的p53氨基酸序列包括将编码经突变的p53氨基酸序列的核苷酸序列引入至APC中。将核苷酸序列引入APC中，使得APC表达并在细胞膜上展示结合至MHC分子的经突变的p53氨基酸序列。编码经突变的p53氨基酸的核苷酸序列可以是RNA或DNA。可以以本领域已知的多种不同方式中的任一种将核苷酸序列引入APC中，如在例如Solheim等人，同上中所述。可用于将核苷酸序列引入APC中的技术的非限制性实例包括转化、转导、转染和电穿孔。在一个实施方案中，该方法可以包括制备超过一种核苷酸序列，每种编码不同的经突变的p53氨基酸序列，以及将每种核苷酸序列引入不同的自体APC群中。在这方面，可以获得自体APC的多个群体，每个群体表达并展示不同的经突变的p53氨基酸序列。
在一个实施方案中，该方法可以包括引入编码多于一种经突变的p53氨基酸序列的核苷酸序列。在这方面，在本发明的一个实施方案中，引入自体APC中的核苷酸序列是串联微基因(TMG)构建体，每种微基因包含p53基因，每种p53基因包括编码不同的经突变的p53氨基酸序列的癌症-特异性p53突变。每种微基因可编码一种p53突变，所述p53突变在p53突变的每一侧上侧接有来自内源性p53蛋白的任何适合数量的连续氨基酸，如本文关于本发明其他方面所述。构建体中的微基因的数量不受限制，并且可以包括例如约5、约10、约11、约12、约13、约14、约15、约20、约25或更多，或由前述值的任两个限定的范围。在本发明的一个实施方案中，TMG构建体编码SEQ ID NO:2-13的一种或多种经突变的p53肽。例如，TMG构建体可以编码SEQ ID NO:14的氨基酸序列。APC表达由TMG构建体编码的经突变的p53氨基酸序列，并在细胞膜上展示与MHC分子结合的经突变的p53氨基酸序列。在一个实施方案中，该方法可以包括制备超过一种TMG构建体，每肿构建体编码不同组的经突变的p53氨基酸序列，并且将每个TMG构建体引入不同的自体APC群体中。在这一点上，可以获得多个自体APC群体，每个群体表达并展示由不同TMG构建体编码的经突变的p53氨基酸序列。
该方法可以包括培养患者的自体T细胞与呈递经突变的p53氨基酸序列的自体APC。T细胞可从患者中的许多来源获得，包括但不限于肿瘤、血液、骨髓、淋巴结、胸腺或其他组织或流体。T细胞可以包括任何类型的T细胞，并且可以处于任何发育阶段，包括但不限于CD4+/CD8+双阳性T细胞，CD4+辅助T细胞如Th1和Th2细胞，CD8+T细胞(如细胞毒性T细胞)，肿瘤浸润细胞(如肿瘤浸润淋巴细胞(TIL))，外周血T细胞，记忆T细胞，初始T细胞等。T细胞可为CD8+T细胞、CD4+T细胞，或CD4+和CD8+T细胞两者。该方法可包括共培养自体T细胞和自体APC，使得T细胞以一种方式遇到由APC呈递的经突变的p53氨基酸序列以使自体T细胞特异性结合至并免疫识别由APC呈递的经突变的p53氨基酸序列。在本发明的一个实施方案中，将自体T细胞与自体APC直接接触共培养。
该方法可以包括选择如下自体T细胞：其(a)与呈递经突变的p53氨基酸序列的自体APC共培养，和(b)对在由患者表达的MHC分子的情况下呈递的经突变的p53氨基酸序列具有抗原特异性。如本文所用的短语“抗原特异性”意指自体T细胞可以特异性结合指并免疫识别由癌症-特异性p53突变编码的经突变的p53氨基酸序列。选择可以包括鉴定对突变的p53氨基酸序列具有抗原特异性的T细胞，并将它们与对经突变的p53氨基酸序列不具有抗原特异性的T细胞分离。可以以任何适合的方式选择对经突变的p53氨基酸序列具有抗原特异性的自体T细胞。在本发明的一个实施方案中，该方法包括如通过与T细胞生长因子(诸如白介素(IL)-2或IL-15)共培养或如本文关于本发明的其他方面所述在选择自体T细胞之前来扩大自体T细胞的数量。在本发明的一个实施方案中，该方法不包括在选择自体T细胞之前用诸如IL-2或IL-15的T细胞生长因子来扩大自体T细胞的数量。
例如，当自体T细胞与呈递突变的p53氨基酸序列的APC共培养后，对突变的p53氨基酸序列具有抗原特异性的T细胞可以表达多种T细胞激活标记中的任一种或多种，其可用于鉴定对突变的p53氨基酸序列具有抗原特异性的那些T细胞。此类T细胞激活标记可包括但不限于程序性细胞死亡1(PD-1)、淋巴细胞-激活基因3(LAG-3)、T细胞免疫球蛋白和粘蛋白结构域3(TIM-3)、4-1BB、OX40和CD107a。因此，在本发明的一个实施方案中，选择对突变的p53氨基酸序列具有抗原特异性的自体T细胞包括选择表达以下中的任一种或多种的T细胞：PD-1、LAG-3、TIM-3、4-1BB、OX40和CD107a。可以使用本领域已知的多种技术中的任一种，诸如例如荧光激活的细胞分选(FACS)或磁激活的细胞分选，基于标记的表达来对表达一种或多种T细胞激活标志物的细胞进行分选，如在如Turcotte等人,Clin.Cancer Res.,20(2):331-43(2013)和Gros等人,J.Clin.Invest.,124(5):2246-59(2014)中所述。
在本发明的另一个实施方案中，选择对突变的p53氨基酸序列具有抗原特异性的自体T细胞包括选择如下T细胞：(i)与由阴性对照分泌的一种或多种细胞因子分泌的量相比，在与呈递经突变的p53氨基酸序列的APC共培养之后分泌更大量的一种或多种细胞因子，或(ii)其中与分泌一种或多种细胞因子的阴性对照T细胞的数量相比，至少两倍数量的T细胞在与呈递经突变的p53氨基酸序列的APC共培养后分泌一种或多种细胞因子。一种或多种细胞因子可以包含任何细胞因子，其由T细胞分泌是T细胞激活的特征(如，由T细胞表达的T细胞受体(TCR)特异性结合至并免疫识别经突变的p53氨基酸序列)。其分泌是T细胞激活的特征的细胞因子的非限制性实例包括IFN-γ、IL-2和肿瘤坏死因子α(TNF-α)、粒细胞/单核细胞菌落刺激因子(GM-CSF)、IL-4、IL-5、IL-9、IL-10、IL-17和IL-22。
例如，如果与由阴性对照分泌的IFN-γ的量相比，T细胞在与(a)用一定浓度的包含突变的p53氨基酸序列的肽(如约0.05ng/mL至约10μg/mL，如0.05ng/mL、0.1ng/mL、0.5ng/mL、1ng/mL、5ng/mL、100ng/mL、1μg/mL、5μg/mL或10μg/mL)脉冲的抗原-阴性APC或(b)已引入编码经突变的p53氨基酸序列的核苷酸序列于其中的APC共培养之后分泌至少两倍IFN-γ，则可认为自体T细胞对经突变的p53氨基酸序列具有“抗原特异性”。阴性对照可以是例如与以下共培养的自体T细胞(如，源自外周血单核细胞(PBMC))：(a)用相同浓度的无关肽(如，野生型氨基酸序列，或具有与经突变的p53氨基酸序列不同的序列的一些其他肽)脉冲的抗原-阴性APC，或(b)已将编码无关肽序列的核苷酸序列引入其中的APC。如果与阴性对照(例如上述的阴性对照)相比，T细胞在与用更高浓度的包含经突变的p53氨基酸序列的肽脉冲的抗原-阴性APC共培养之后分泌更大量的IFN-γ，则自体T细胞还可对经突变的p53氨基酸序列具有“抗原特异性”。IFN-γ分泌可以通过本领域已知的方法，诸如例如酶联免疫吸附测定(ELISA)来测量。
可替代地或另外地，如果与分泌IFN-γ的阴性对照T细胞的数量相比，至少两倍数量的T细胞在与(a)用一定浓度的包含经突变的p53氨基酸序列的肽脉冲的抗原-阴性APC或(b)已引入编码经突变的p53氨基酸序列的核苷酸序列于其中的APC共培养之后分泌IFN-γ，则可认为自体T细胞对经突变的p53氨基酸序列具有“抗原特异性”。肽和阴性对照的浓度可以如本文关于本发明的其他方面所述。分泌IFN-γ的细胞的数量可以通过本领域已知的方法诸如例如ELISPOT来测量。
可替代地或另外地，如果与通过ELISPOT检测的与相同靶细胞共培养的阴性对照T细胞的点的数量相比，通过ELISPOT检测到在与以下共培养之后的T细胞的至少两倍数量的点：(a)用低浓度的经突变的p53肽脉冲的抗原-阴性、可适用的HLA分子阳性靶细胞或(b)已引入编码经突变的p53的核苷酸序列于其中以使得靶细胞表达经突变的p53的抗原-阴性、可适用的HLA分子阳性靶细胞，则可认为自体T细胞对经突变的p53具有“抗原特异性”。肽和阴性对照的浓度可以如本文关于本发明的其他方面所述。
可替代地或另外地，如果通过ELISPOT检测到在与以下共培养之后表达TCR的T细胞的大于约50个点：(a)用低浓度的经突变的p53肽脉冲的抗原-阴性、可适用的HLA分子阳性靶细胞或(b)已引入编码经突变的p53的核苷酸序列于其中以使得靶细胞表达经突变的p53的抗原-阴性、可适用的HLA分子阳性靶细胞，则可认为自体T细胞对经突变的p53具有“抗原特异性”。肽的浓度可以如本文关于本发明的其他方面所述。
尽管对经突变的p53氨基酸序列具有抗原特异性的T细胞既可(1)表达本文所述的任一种或多种T细胞激活标志物，也可(2)分泌更大量的如本文所述的一种或多种细胞因子，但在本发明的一个实施方案中，对经突变的p53氨基酸序列具有抗原特异性的T细胞可以表达任一种或多种T细胞激活标志物，而不会分泌更大量的一种或多种细胞因子，或者可以分泌更大量的一种或多种细胞因子而不表达任一种或多种T细胞激活标志物。
在本发明的另一个实施方案中，选择对突变的p53氨基酸序列具有抗原特异性的自体T细胞包括选择性地生长对突变的p53氨基酸序列具有抗原特异性的自体T细胞。在这方面，该方法可以包括以此类方式共培养自体T细胞与自体APC，以有利于对突变的p53氨基酸序列具有抗原特异性的T细胞的生长超过对突变的p53氨基酸序列不具有抗原特异性的T细胞。因此，提供了与对突变的p53氨基酸序列不具有抗原特异性的T细胞相比，具有更高比例的对突变的p53氨基酸序列具有抗原特异性的T细胞的T细胞群。
在本发明的一个实施方案中，该方法还包括从患者获得肿瘤的多个碎片，分别将来自多个碎片的每一个的自体T细胞与呈递突变的p53氨基酸序列的自体APC共同培养(如本文中关于本发明的其他方面所述)，和分别评估来自多个碎片中的每一个的T细胞对突变的p53氨基酸序列的抗原特异性(如本文中关于本发明的其他方面所述)。
在其中T细胞与表达多种经突变的p53氨基酸序列(如，由TMG构建体编码的多种突变的p53氨基酸序列或脉冲至自体APC上的肽汇集物中多种经突变的p53氨基酸序列)的自体APC共培养的本发明的一个实施方案中，选择自体T细胞还可包括分别评估自体T细胞对多种突变的p53氨基酸序列中的每一种的抗原特异性。例如，如本文关于本发明的其他方面所述，本发明的方法还可以包括分别诱导患者的自体APC呈递由构建体编码(或包含在汇集物中)的每种经突变的p53氨基酸序列(例如，通过提供分别的APC群，每个呈递由构建体编码(或包含在汇集物中)的不同的经突变的p53氨基酸序列)。如本文关于本发明的其他方面所述，所述方法还可包括将患者的自体T细胞与呈递每种突变的p53氨基酸序列的不同自体APC群分别共培养。如本文关于本发明的其他方面所述，所述方法还可以包括分别选择以下的自体T细胞：(a)与呈递突变的p53氨基酸序列的自体APC共培养，和(b)对在由患者表达的MHC分子的情况下呈递的经突变的p53氨基酸序列具有抗原特异性。在这方面，所述方法可以包括确定哪些由编码多种突变的p53氨基酸序列(或包含在汇集物中)的TMG构建体编码的突变的p53氨基酸序列被自体T细胞在免疫学上识别(如，通过消除的过程)。
在本发明的一个实施方案中，方法还包括扩大选定的自体T细胞的数量以获得对由癌症-特异性p53突变编码的经突变的p53氨基酸序列具有抗原特异性的T细胞群。选定细胞的数量的扩大可通过本领域已知的多种方法中的任一种实现，如例如在美国专利8,034,334；美国专利8,383,099；美国专利申请公开No.2012/0244133；Dudley等人,J.Immunother.,26:332-42(2003)；和Riddell等人,J.Immunol.Methods,128:189-201(1990)中所述。在一个实施方案中，T细胞的数量的扩大通过培养T细胞与OKT3抗体、IL-2和饲养PBMC(如，经辐照的同种异体PBMC)来进行。在这方面，本发明的方法可以有利地产生大量的对经突变的p53氨基酸序列具有抗原特异性的T细胞。
通过本发明方法分离的T细胞可用于制备用于过继细胞疗法的细胞。在这方面，本发明的一个实施方案提供了制备对由癌症-特异性p53突变编码的经突变的p53氨基酸序列具有抗原特异性的T细胞群的方法，该方法包括分离如在本文中关于本发明的其他方面所述的T细胞，并且扩大选定自体T细胞的数量以获得对由癌症-特异性突变编码的经突变的p53氨基酸序列具有抗原特异性的T细胞群。如本文关于本发明的其他方面所述，可以进行选定细胞的数量的扩大。
本发明的另一个实施方案提供了分离对由癌症-特异性p53突变编码的经突变的p53氨基酸序列具有抗原特异性的T细胞受体(TCR)或其抗原结合部分的方法。如本文关于本发明的其他方面所述，该方法可以包括分离对由癌症-特异性p53突变编码的经突变的p53氨基酸序列具有抗原特异性的T细胞。
本发明的方法还可以包括从选定T细胞中分离编码TCR或其抗原结合部分的核苷酸序列，其中TCR或其抗原结合部分对由癌症-特异性p53突变编码的经突变的p53氨基酸序列具有抗原特异性。在本发明的一个实施方案中，在分离编码TCR或其抗原结合部分的核苷酸序列之前，可以扩大对经突变的p53氨基酸序列具有抗原选择性的选定T细胞的数量。如本文关于本发明的其他方面所述，可以进行选定细胞数量的扩大。在本发明的另一个实施方案中，在分离编码TCR或其抗原结合部分的核苷酸序列之前，没有扩大对经突变的p53氨基酸序列具有抗原特异性的选定T细胞的数量。例如，可以从单个细胞分离TCR或其抗原结合部分。
如本文所用，TCR的“抗原结合部分”是指作为TCR一部分的包含TCR连续氨基酸的任何部分，前提是抗原结合部分特异性结合至经突变的p53氨基酸序列，如本文关于本发明的其他方面所述。术语“抗原结合部分”是指TCR的任何部分或片段，所述部分或片段作为TCR一部分的保留了TCR(母体TCR)的生物学活性。抗原结合部分涵盖了例如，TCR中保留与经突变的p53氨基酸序列特异性结合，或与母体TCR相比以相似的程度、相同的程度或以更高的程度检测、治疗或预防癌症的能力的那些部分。关于母体TCR，功能部分可包含例如约10％、约25％、约30％、约50％、约68％、约80％、约90％、约95％或更多的母体TCR。
抗原结合部分可包含TCR的α链和β链中任一条或两条的抗原结合部分，诸如包含TCR的α链和/或β链的可变区的互补决定区(CDR)1、CDR2和CDR3中的一个或多个的部分。在本发明的一个实施方案中，抗原结合部分可包含以下的氨基酸序列：α链的CDR1(CDR1α)、α链的CDR2(CDR2α)、α链的CDR3(CDR3α)、β链的CDR1(CDR1β)、β链的CDR2(CDR2β)、β链的CDR3(CDR3β)或其任何组合。优选地，抗原结合部分包含TCR的CDR1α、CDR2α和CDR3α的氨基酸序列；CDR1β、CDR2β和CDR3β的氨基酸序列；或所有CDR1α、CDR2α、CDR3α、CDR1β、CDR2β和CDR3β的氨基酸序列。
在本发明的一个实施方案中，抗原结合部分可以包括，例如，TCR的可变区，其包括上述CDR区的组合。在这方面，抗原结合部分可以包含TCR的α链的可变区(Vα)的氨基酸序列，β链的可变区的氨基酸序列(Vβ)或Vα和Vβ两者的氨基酸序列。
在本发明的一个实施方案中，抗原结合部分可包含可变区和恒定区的组合。在这方面，抗原结合部分可包含TCR的全长α或β链，或α和β链两者。
从选定T细胞中分离编码TCR或其抗原结合部分的核苷酸序列可以本领域已知的任何适合的方式进行。例如，该方法可以包括使用已建立的分子克隆技术和试剂诸如例如使用TCR-α和-β链恒定引物的cDNA末端5’快速扩增(RACE)聚合酶链式反应(PCR)，从选定T细胞中分离RNA，并对TCR或其抗原结合部分进行测序。可替代地或另外地，可用于分离TCR核酸序列的技术和系统可包括例如单细胞逆转录聚合酶链式反应(RT-PCR)、生物信息重建、有限稀释克隆、Fluidigm系统(Fluidigm Corporation,South San Francisco,CA)，通过频率配对对TCRα和TCRβ链进行深度测序，来自Adaptive Biotechnologies(Seattle,WA)的鉴定TCRα和β链对的PAIRSEQ方法，以及其组合。
在本发明的一个实施方案中，所述方法可以包括使用例如如Green等人(Eds.),Molecular Cloning:A Laboratory Manual,Cold Spring Harbor Laboratory Press；第4版(2012)所述的确定的分子克隆技术将编码TCR或其抗原结合部分的核苷酸序列克隆至重组表达载体中。为了本文的目的，术语“重组表达载体”意指经遗传修饰的寡核苷酸或多核苷酸构建体，当该构建体包含编码mRNA、蛋白、多肽或肽的核苷酸序列并且载体在足以使mRNA、蛋白、多肽或肽在细胞内表达的条件下与细胞接触时，其允许宿主细胞表达mRNA、蛋白、多肽或肽。载体可以不是作为整体天然存在的。然而，载体的部分可以是天然存在的。重组表达载体可以包含任何类型的核苷酸，包括但不限于DNA(如互补DCA(cDNA))和RNA，其可以是单链或双链的、合成的或部分地从天然来源获得的并且可以含有天然、非天然或改变的核苷酸。重组表达载体可以包含天然存在的、非天然存在的核苷酸间键联，或两种类型的键联。优选地，非天然存在或改变的核苷酸或核苷酸间键联不阻碍载体的转录或复制。
重组表达载体可以是任何适合的重组表达载体，并且可以用于转化或转染任何适合的宿主细胞。适合的载体包括经设计用于繁殖和扩增或用于表达或两者的那些，诸如质粒和病毒。载体可以选自：转座子/转座酶、pUC系列(Fermentas Life Sciences)、pBluescript系列(Stratagene,LaJolla,CA)、pET系列(Novagen,Madison,WI)、pGEX系列(Pharmacia Biotech,Uppsala,Sweden)和pEX系列(Clontech,Palo Alto,CA)。也可以使用噬菌体载体，诸如λGT10、λGT11、λZapII(Stratagene)、λEMBL4和λNM1149。植物表达载体的实例包括pBI01、pBI101.2、pBI101.3、pBI121和pBIN19(Clontech)。动物表达载体的实例包括pEUK-Cl、pMAM和pMAMneo(Clontech)。优选地，重组表达载体是病毒载体，如逆转录病毒载体。
通过本发明的方法分离的TCR或其抗原结合部分可用于制备用于过继细胞疗法的细胞。在这方面，本发明的一个实施方案提供了制备表达对由癌症-特异性p53突变编码的经突变的p53氨基酸序列具有抗原特异性的TCR或其抗原结合部分的细胞群的方法，该方法包括分离TCR或其抗原结合部分(如本文关于本发明的其他方面所述)并将编码分离的TCR或其抗原结合部分的核苷酸序列引入宿主细胞中，以获得表达TCR或其抗原结合部分的细胞。
可以以本领域已知的多种不同方式中的任一种，如例如Green等人(同上)所述，进行将编码经分离的TCR或其抗原结合部分的核苷酸序列(如重组表达载体)引入宿主细胞中。可用于将核苷酸序列引入宿主细胞中的技术的非限制性实例包括转化、转导、转染、转座和电穿孔。
引入编码TCR或其抗原结合部分的核苷酸序列的宿主细胞可以是可含有重组表达载体的任何类型的细胞。宿主细胞可以是真核细胞，如植物、动物、真菌或藻类，或者可以是原核细胞，如细菌或原生动物。宿主细胞可以是培养的细胞或原代细胞，即直接从生物体如人类中分离。宿主细胞可以是贴壁细胞或悬浮细胞，即在悬浮液中生长的细胞。适合的宿主细胞是本领域已知的，并且包括例如DH5α大肠埃希氏菌细胞、中国仓鼠卵巢细胞、猴VERO细胞、COS细胞、HEK293细胞等。为了扩增或复制重组表达载体，宿主细胞优选是原核细胞，如DH5α细胞。为了产生TCR或其抗原结合部分，宿主细胞优选是哺乳动物细胞。最优选地，宿主细胞是人细胞。尽管宿主细胞可以属于任何细胞类型、可以源自任何类型的组织并且可以属于任何发育阶段，但是宿主细胞优选是PBL或PBMC。更优选地，宿主细胞是T细胞。
在本发明的一个实施方案中，PBMC包括T细胞。T细胞可以是任何类型的T细胞。不受特定理论或机制的束缚，认为与分化程度更高的“较老”T细胞相比，分化程度更低的“较年轻”T细胞可能与更高的体内持久性、增殖和抗肿瘤活性的任一种或多种有关。因此，本发明的方法可以有利地鉴定和分离对经突变的p53氨基酸序列具有抗原特异性的TCR或其抗原结合部分，并将TCR或其抗原结合部分引入与“较老”T细胞(如，患者肿瘤中的效应细胞)相比可提供更高的体内持久性、增殖和抗肿瘤活性中的任一种或多种的“较年轻”T细胞中。
在本发明的一个实施方案中，本发明的方法鉴定并分离对由频发(也称为“热点”)癌症-特异性p53突变编码的经突变的p53氨基酸序列具有抗原特异性的TCR或抗原结合部分。在这方面，该方法可以包括将编码经分离的TCR或其抗原结合部分的核苷酸序列引入对于患者是同种异体的宿主细胞中。例如，所述方法可以包括将编码经分离的TCR或其抗原结合部分的核苷酸序列引入来自另一名患者的宿主细胞中，所述另一名患者的肿瘤在相同的MHC分子的背景下表达相同的p53突变。
在本发明的一个实施方案中，所述方法还包括扩大表达TCR或其抗原结合部分的宿主细胞的数量。例如，如本文关于本发明的其他方面所述，可以扩大宿主细胞的数量。在这方面，本发明的方法可以有利地产生大量的对经突变的p53氨基酸序列具有抗原特异性的T细胞。
本发明的另一个实施方案提供了根据本文关于本发明其他方面所述的任何方法制备的经分离的细胞群。细胞群体可以是异质群体，其除了至少一种其他细胞之外还包括对由癌症-特异性p53突变编码的经突变的p53氨基酸序列具有抗原特异性的T细胞，所述其他细胞如对由癌症-特异性p53突变编码的经突变的p53氨基酸序列不具有抗原特异性的PBMC，或除了T细胞以外的细胞，如B细胞、巨噬细胞、嗜中性粒细胞、红细胞、肝细胞、内皮细胞。肌肉细胞、脑细胞等。可选地，细胞群可以是基本上同质的群，其中该群主要包括(如，基本上由以下组成)对由癌症-特异性p53突变编码的经突变的p53氨基酸序列具有抗原特异性的T细胞。所述群也可以是细胞的克隆群，其中群体的所有细胞都是单个T细胞的克隆，使得群体中的所有细胞都对由癌症-特异性p53突变编码的经突变的p53氨基酸序列具有抗原特异性。如本文所述，在本发明的一个实施方案中，细胞群是包含对由癌症-特异性p53突变编码的经突变的p53氨基酸序列具有抗原特异性的T细胞的克隆群。在本发明的一个实施方案中，细胞群体的约1％至约100％，例如约1％、约5％、约10％、约15％、约20％、约25％、约30％、约35％、约40％、约45％、约50％、约55％、约60％、约65％、约70％、约75％、约80％、约85％、约90％、约95％、约96％、约97％、约98％、约99％或约100％，或由前述值的任两个限定的范围的包含对经突变的p53氨基酸序列具有抗原特异性的T细胞。不受特定理论或机制的束缚，认为包含高比例的对经突变的p53氨基酸序列具有抗原特异性的T细胞的细胞群可以有利地具有较低比例的无关细胞，所述无关细胞可阻碍T细胞的功能，如T细胞靶向癌细胞的破坏和/或治疗或预防癌症的能力。
可以将本发明的细胞群配制成组合物，诸如药物组合物。在这方面，本发明提供了包含本发明的任何细胞群和药物上可接受的载体的药物组合物。本发明的药物组合物可以包含与另一种或多种药学活性剂或药物(诸如化学治疗剂，如天冬酰胺酶、白消安、卡铂、顺铂、道诺霉素、多柔比星、氟尿嘧啶、吉西他滨、羟基脲、甲氨蝶呤、紫杉醇、利妥昔单抗、长春碱，长春新碱等)组合的本发明的细胞群。
优选地，载体是药学上可接受的载体。关于药物组合物，载体可以是所考虑的本发明特定细胞群常规使用的那些中任一种。此类药学上可接受的载体是本领域技术人员众所周知的，并且容易被公众使用。优选地，药学上可接受的载体是在使用条件下不具有有害的副作用或毒性的载体。
载体的选择将部分地由本发明的特定细胞群以及用于施用本发明的细胞群的特定方法决定。因此，有多种本发明的药物组合物的适合制剂。适合制剂可以包括用于肠胃外、皮下、静脉内、肌内、动脉内、肿瘤内、鞘内或腹膜内施用的那些中任一种。可以使用多于一种的途径来施用本发明的细胞群，并且在某些情况下，特定的途径可以提供比另一种途径更直接和更有效的响应。
优选地，本发明的细胞群通过注射如静脉内施用。当要施用本发明的细胞群时，用于注射用细胞的药物上可接受的载体可以包括任何等渗载体，诸如例如生理盐水(约0.90％w/v的NaCl水溶液，约300mOsm/L NaCl水溶液，或约9.0g NaCl/L水)、NORMOSOL R电解质溶液(Abbott,Chicago,IL)、PLASMA-LYTE A(Baxter,Deerfield,IL)、约5％葡萄糖水溶液或林格氏乳酸盐。在一个实施方案中，药学上可接受的载体补充有人血清白蛋白。
预期本发明的细胞群和药物组合物可以用于治疗或预防癌症的方法中。不受特定理论或机制的束缚，本发明的T细胞被认为特异性结合至由癌症-特异性p53突变编码的经突变的p53氨基酸序列，使得细胞表达的TCR能够介导针对表达经突变的p53氨基酸序列的靶细胞的免疫反应。在这方面，本发明的一个实施方案提供了治疗或预防哺乳动物中的癌症的方法，其包括以有效治疗或预防哺乳动物中的癌症的量向哺乳动物施用本文所述的任何药物组合物或细胞群。
如本文所用的，术语"治疗"和"预防"以及由此衍生的词不一定意味着100％或完全的治疗或预防。而是，存在不同程度的治疗或预防，本领域普通技术人员认为这具有潜在的益处或治疗效果。在这方面，本发明的方法可以在哺乳动物中提供任何量的任何水平的癌症治疗或预防。此外，通过本发明的方法提供的治疗或预防可以包括治疗或预防所治疗或预防的癌症的一种或多种病状或症状。例如，治疗或预防可以包括促进肿瘤的消退。此外，出于本文的目的，"预防"可以涵盖延迟癌症或其症状或病状的发作。
为了本发明的目的，所施用的本发明细胞群或药物组合物的量或剂量(如，当施用本发明的细胞群时的细胞数)应足以在合理的时间范围内在哺乳动物中实现如治疗或预防应答。例如，本发明的细胞群或药物组合物的剂量应足以与由癌症-特异性p53突变编码的经突变的p53氨基酸序列结合，或在从施用时起约2小时或更久(如12至24或更多小时)时间段内检测、治疗或预防癌症。在某些实施方案中，时间段可以甚至更长。剂量将由所施用的特定本发明细胞群或药物组合物的功效以及哺乳动物(如人)的状况以及待治疗的哺乳动物(如人)的体重来确定。
用于确定施用剂量的许多测定法是本领域已知的。为了本发明的目的，测定可用于确定要向哺乳动物施用的起始剂量，所述测定包括比较在各自给予不同剂量的T细胞的一组哺乳动物中，在施用给定剂量的此类T细胞至哺乳动物之后，裂解靶细胞或由T细胞分泌IFN-γ的程度。施用一定剂量后，裂解靶细胞或分泌IFN-γ的程度可以通过本领域已知的方法来测定。
本发明的细胞群或药物组合物的剂量也将由可能伴随施用特定的本发明的细胞群或药物组合物的任何不良副作用的存在、性质和程度来确定。通常，主治医师将考虑各种因素，诸如年龄、体重、总体健康状况、饮食、性别、待施用的本发明的细胞群或药物组合物、施用途径和治疗的疾患的严重程度，决定治疗每个个体患者的本发明的细胞群或药物组合物的剂量。
在其中待施用本发明的细胞群的一个实施方案中，每次输注施用的细胞数可以变化，例如在100万个至1000亿个细胞的范围内；然而，低于或高于该示例性范围的量在本发明的范围内。例如，本发明的宿主细胞的每日剂量可以是约100万个至约1500亿个细胞(如约500万个细胞、约2500万个细胞、约5亿个细胞、约10亿个细胞、约50亿个细胞、约200亿个细胞、约300亿个细胞、约400亿个细胞、约600亿个细胞、约800亿个细胞、约1000亿个细胞、约1200亿个细胞、约1300亿个细胞、约1500亿个细胞，或由前述值的任两个限定的范围)，优选约1000万个细胞至约1300亿个细胞(如约2000万个细胞、约3000万个细胞、约4000万个细胞、约6000万个细胞、约7000万个细胞、约8000万个细胞、约9000万个细胞、约100亿个细胞、约250亿个细胞、约500亿个细胞、约750亿个细胞、约900亿个细胞、约1000亿个细胞、约1100亿个细胞、约1200亿个细胞、约1300亿个细胞，或由前述值的任两个限定的范围)，更优选约1亿个细胞至约1300亿个细胞(如约1.2亿个细胞、约2.5亿个细胞、约3.5亿个细胞、约4.50亿个细胞、约6.50亿个细胞、约8亿个细胞、约9亿个细胞、约30亿个细胞、约300亿个细胞、约450亿个细胞、约500亿个细胞、约750亿个细胞、约900亿个细胞、约1000亿个细胞、约1100亿个细胞、约1200亿个细胞、约1300亿个细胞，或由前述值的任两个限定的范围)。
为了本发明方法的目的，其中施用细胞群，所述细胞可以是哺乳动物同种异体的或自体的细胞。优选地，细胞对于哺乳动物是自体的。
本发明的另一个实施方案提供了用于治疗或预防哺乳动物中的癌症的本文所述的经分离的细胞群或药物组合物中的任一种。
就本发明的方法而言，癌症可以是任何癌症，包括以下中的任一种：急性淋巴细胞癌，急性髓细胞性白血病，肺泡横纹肌肉瘤，骨癌，脑癌，癌，乳腺癌，肛门癌、肛管癌或肛门直肠癌，眼癌，肝内胆管癌，关节癌，颈癌、胆囊癌或胸膜癌，鼻癌、鼻腔癌或中耳癌，口腔癌，阴道癌，外阴癌，慢性淋巴细胞性白血病，慢性髓样癌，结肠癌，结直肠癌，子宫内膜癌，食道癌，子宫颈癌，胃肠道类癌瘤，神经胶质瘤，霍奇金淋巴瘤，下咽癌，肾癌，喉癌，肝癌，肺癌，恶性间皮瘤，黑素瘤，多发性骨髓瘤，鼻咽癌，非霍奇金淋巴瘤，口咽癌，卵巢癌，阴茎癌，胰腺癌，腹膜癌、网膜癌和肠系膜癌，舌咽癌，前列腺癌，直肠癌，肾癌，皮肤癌，小肠癌，软组织癌，胃癌，睾丸癌，甲状腺癌，子宫癌，输尿管癌和尿道膀胱癌。在一个优选的实施方案中，癌症是表达突变的p53的癌症。癌症可以在SEQ ID NO:1的位置175、220、245、248、249、273或282中的一个或多个处表达具有突变的p53。癌症可表达具有以下人p53突变中的一种或多种的p53：R175H、Y220C、G245D、G245S、R248L、R248Q、R248W、R249S、R273H、R273C、R273L或R282W。优选地，癌症是上皮癌或胆管癌、黑素瘤、结肠癌、直肠癌、卵巢癌、子宫内膜癌、非小细胞肺癌(NSCLC)、成胶质细胞瘤、子宫颈癌、头颈癌、乳房癌、胰腺癌或膀胱癌。
本发明方法中提及的哺乳动物可以是任何哺乳动物。如本文所用，术语“哺乳动物”是指任何哺乳动物，包括但不限于啮齿目的哺乳动物，诸如小鼠和仓鼠，以及兔形目的哺乳动物，诸如兔。优选地，哺乳动物来自食肉目，包括猫科动物(猫)和犬科动物(狗)。优选地，哺乳动物来自偶蹄目，包括牛科动物(牛)和猪科动物(猪)，或属于奇蹄目，包括马科动物(马)。优选地，哺乳动物属于灵长目、阔鼻小目或Simoid(猴)，或属于类人猿亚目(人类和猿类)。更优选的哺乳动物是人类。
以下实施例进一步说明了本发明，但是当然不应理解为以任何方式限制其范围。
实施例
在以下实施例中描述的实验中使用表1-3中列出的氨基酸序列。
表1
Figure BDA0002430898550000311
表2列出了表1的肽的野生型形式。
表2
Figure BDA0002430898550000322
表3
Figure BDA0002430898550000321
Figure BDA0002430898550000331
实施例1
该实施例证实了通过在自体T细胞内共培养经诱导以表达突变的p53的自体APC来鉴定患者4141中的抗-突变的p53 T细胞(“p53热点突变通用筛选”)。该实施例还证实了来自患者4141的TCR的分离和特异的反应性。
如图1和45-48针对患者4141所述进行实验。来自患者4141的TIL片段F12和输液袋TIL(Rx1)及来自患者4196的p53-R175H-特异性TCR或模拟物转导的T细胞用作效应器。T细胞效应器与HLA-A*02:01APCs(对于患者4141是自体)的共培养物(1)用由无关、WT p53或突变的p53序列组成的TMG电穿孔，或者(2)用肽媒介物(DMSO)或由WT p53-R175序列或突变的p53-R175H序列组成的经纯化的(>95％，通过HPLC)25个氨基酸的肽脉冲。仅T细胞(无靶标)是阴性对照，并且PMA和Iono是阳性对照(格条)。在37℃下进行共培养过夜。使用ELISPOT测定评价IFN-γ的分泌。结果示于图1中。
将自体APC用编码无关突变、WT p53序列或包含R175H的突变的p53序列的TMG转染。单独的培养基以及PMA和离子霉素分别为阴性对照和阳性对照。第二天，将来自患者4141的TIL(片段培养物12)与TMG-转染的APC在37℃下共培养过夜。通过ELISPOT评价IFN-γ的分泌。对于淋巴细胞→活细胞(PI阴性)→CD3+(T细胞)→CD4-CD8+设门后，通过流式细胞术评价4-1BB的表达。结果示于图45中。
将Cos7细胞(每孔2.5x104个)涂铺在平底96孔板的孔上。第二天，将细胞用来自患者4141的单独HLA等位基因以及无额外基因、WT TP53TMG或含有p53-R175H序列的突变的TP53 TMG共转染。第二天，将来自患者4141的对p53-R175H具有特异性的TIL(片段培养物12)与转染的Cos7细胞共培养，并在37℃下孵育过夜。通过ELISPOT评价IFN-γ的分泌。结果示于图46中。
将表达模拟物(无TCR)或4141-TCR1a2的T细胞与T2肿瘤细胞(表达HLA-A*02:01)共培养。将T2细胞在37℃下用肽媒介物(DMSO)或由WT p53-R175肽HMTEVVRRC(SEQ ID NO:532)或经突变的p53-R175H肽HMTEVVRHC(SEQ ID NO:530)组成的纯化的(>95％，通过HPLC)肽脉冲。单独的培养基及PMA和离子霉素分别为阴性对照和阳性对照。在37℃下进行共培养过夜。IFN-γ的分泌通过ELISA评价。结果示于图47中。
将表达4141-TCR1a2的T细胞与Saos2细胞(p53-NULL和HLA-A*02:01+)在37℃下共培养过夜，这些细胞未经处理，或使得过表达全长p53-R175H蛋白。将分泌的抑制剂(莫能菌素和布雷菲德菌素A)添加至共培养物，以捕获T细胞内的细胞因子。共培养6小时后，将细胞固定并透化，然后针对IL-2、CD107a、IFN-γ和肿瘤坏死因子-α(TNFα)染色。流式细胞术用于基于淋巴细胞门分析共培养物。结果示于图48中。
从患者4141分离的TCR 4141-TCR1a2的序列示于以下。从氨基末端开始，第一加下划线的区是CDR1α(SEQ ID NO:467)，第二加下划线的区是CDR2α(SEQ ID NO:468)，第三加下划线的区是CDR3α(SEQ ID NO:469)，第四加下划线的区是CDR1β(SEQ ID NO:470)，第五加下划线的区是CDR2β(SEQ ID NO:471)，并且第六加下划线的区是CDR3β(SEQ ID NO:472)。粗体区是连接子(SEQ ID NO:26)。从氨基末端开始，第一斜体区是α链恒定区(SEQ IDNO:23)并且第二斜体区是β链恒定区(SEQ ID NO:25)。α链可变区(SEQ ID NO:473)包含从氨基末端开始并且就在α链恒定区开始前结束的序列。β链可变区(SEQ ID NO:474)包含在连接子之后立即开始并且就在β链恒定区开始之前结束的序列。全长α链(SEQ ID NO:475)包含从氨基末端开始并且就在连接子开始之前结束的序列。全长β链(SEQ ID NO:476)包含在连接子之后立即开始并且以羧基末端结束的序列。
如下所述鉴定癌症反应性T细胞。如下所述分离TCR。
TCR名称：4141-TCR1a2
P53突变的识别：R175H
筛选方法：p53“热点”突变通用筛选
共培养以鉴定TCR：共培养4141输液袋TIL与p53mutTMG，和分选CD8+41BB+T细胞
鉴定TCR的方法：单细胞RT-PCR，然后TA TOPO克隆试剂盒(Thermo FisherScientific,Waltham,MA)用于α链
TCR取向：α-β
表达载体：SB转座子
MASIRAVFIFLWLQLDLVNGENVEQHPSTLSVQEGDSAVIKCTYSDSASNYFPWYKQELGKGPQLIIDIRSNVGEKKDQRIAVTLNKTAKHFSLHITETQPEDSAVYFCAASKSAIMVVLQTSSSLELALCLLSSQVNIQNPEPAVYQLKDPRSQDSTLCLFTDFDSQINVPKTMESGTFITDKCVLDMKAMDSKSNGAIAWSNQTSFTCQDIFKETNATYPSSDVPCDATLTEKSFETDMNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSSRAKRSGSGATNFSLLKQAGDVEENPGPMHPQLLGYVVLCLLGAGPLEAQVTQNPRYLITVTGKKLTVTCSQNMNHEYMSWYRQDPGLGLRQIYYSMNV EVTDKGDVPEGYKVSRKEKRNFPLILESPSPNQTSLYFCASSIQQGADTQYFGPGTRLTVLEDLRNVTPPKVSLFEPSKAEIANKQKATLVCLARGFFPDHVELSWWVNGKEVHSGVCTDPQAYKESNYSYCLSSRLRVSATFWHNPRNHFRCQVQFHGLSEEDKWPEGSPKPVTQNISAEAWGRADCGITSASYQQGVLSATILYEILLGKATLYAVLVSTLVVMAMVKRKNS(SEQ ID NO:587)
来自患者4141的4141-TCR1a2的统计数据示于下表4中。
表4
参数 # 频率
总孔 96 100％
CDR3α 未知(TA topO克隆) 不适用
CDR3β 58 60.4％
实施例2
该实施例证实了通过在自体T细胞内共培养被诱导以表达突变的p53的自体APC来鉴定患者4130中的抗-突变的p53 T细胞(“p53热点突变通用筛选”)。
如图2针对患者4130所述进行实验。将来自患者4130的TIL片段(F14、F20和F24)与自体APC共培养，所述自体APC(1)用由无关的、WT p53或经突变的p53序列组成的TMG电穿孔，或(2)用肽媒介物(DMSO)或由WT p53-R273序列或经突变的p53-R273H序列组成的经纯化的(>95％，通过HPLC)25个氨基酸的肽脉冲。在37℃下进行共培养过夜。对于淋巴细胞→活细胞(PI阴性)→CD3+(T细胞)设门后，通过流式细胞术评价4-1BB的表达。结果示于图2中。
实施例3
该实施例证实了通过在自体T细胞内共培养被诱导以表达突变的p53的自体APC来鉴定患者4259中的抗-突变的p53 T细胞(“p53热点突变通用筛选”)。该实施例还证实了从患者4259分离的TCR的分离和特异的反应性。
如图3-8和49-53针对患者4259所述进行实验。将来自患者4259的TIL片段(n＝18)与用由无关的、WT p53或突变的p53序列组成的TMG电穿孔的自体APC共培养。在37℃下进行共培养过夜。使用ELISPOT测定评价IFN-γ的分泌。结果示于图3中。对淋巴细胞→活细胞(PI阴性)→CD3+(T细胞)设门后，通过流式细胞术评价4-1BB的表达。结果示于图4-5中。
将来自患者4259的TIL片段(n＝18)与用肽媒介物(DMSO)或由WT p53-Y220序列或突变的p53-Y220C序列组成的经纯化的(>95％，通过HPLC)25个氨基酸的肽脉冲的自体APC共培养。在37℃下进行共培养过夜。使用ELISPOT测定评价IFN-γ的分泌。结果示于图6中。对于淋巴细胞→活细胞(PI阴性)→CD3+(T细胞)设门后，通过流式细胞术评价4-1BB的表达。结果示于图7-8中。
将来自患者4259的TIL片段培养物(no.6)与自体APC共培养，所述自体APC(1)用由无关、WT p53或经突变的p53序列组成的TMG电穿孔，或(2)用肽媒介物(DMSO)或由WT p53-Y220序列或经突变的p53-Y220C序列组成的经纯化的(>95％，通过HPLC)25-个氨基酸的肽脉冲。在37℃下进行共培养过夜。对于淋巴细胞→活细胞(PI阴性)→CD3+(T细胞)设门后，通过流式细胞术评价4-1BB的表达。结果示于图49中。
将自体APC在37℃下用降低浓度的25-个氨基酸的肽(对应于WT p53-Y220或突变的p53-Y220C序列)脉冲2小时。将来自患者4259的TIL片段培养物(no.6)与肽-脉冲的APC共培养。对于淋巴细胞→活细胞(PI阴性)→CD3+(T细胞)设门后，通过流式细胞术测定4-1BB的表达。结果示于图50中。
将自体抗原呈递细胞在37℃下用DMSO、WT p53-Y220肽RNTFRHSVVVPYE(SEQ IDNO:533)或突变的p53-Y220C肽RNTFRHSVVVPCE(SEQ ID NO:534)脉冲2小时。将过量肽冲走。将来自患者4259的对p53-Y220C具有特异性的TIL(片段培养物6)在37℃下与肽-脉冲的APC共培养过夜。对于淋巴细胞→活细胞(PI阴性)→CD3+(T细胞)设门后，通过流式细胞术评价4-1BB的表达。结果示于图51中。
将Cos7细胞(每孔2.5x104个)涂铺在平底96孔板的孔上。接下来的一天，将细胞与来自患者4259的单独的HLA等位基因共转染。次日，将DMSO或p53-Y220C肽RNTFRHSVVVPCE(SEQ ID NO:534)在经转染的Cos7细胞上脉冲2小时。将过量肽冲走。添加来自患者4259的TIL片段培养物no.6(105个细胞/孔)。将共培养物在37℃下孵育过夜。对于淋巴细胞→活→CD3+(T细胞)→CD8-CD4+设门后，通过流式细胞术测定4-1BB的表达。结果示于图52中。
将患者4259自体的APC在37℃下用对应于WT p53-Y220或经突变的p53-Y220C序列的25-个氨基酸的肽脉冲2小时。将过量肽冲走。将表达4259-F6-TCR的T细胞与肽-脉冲的APC在37℃下共培养过夜。对于淋巴细胞→活细胞(PI阴性)→CD3+(T细胞)设门后，通过流式细胞术评价4-1BB的表达。通过小鼠TCRβ(mTCR)测量导入的TCR。结果示于表5中。
表5
WT p53-Y220 Mut p53-Y220C
4-1BB+/mTCR+ 0.27 5.22
4-1BB-/mTCR- 68.5 73.7
4-1BB+/mTCR- 0.18 1.59
4-1BB-/mTCR+ 31.0 19.5
肿瘤细胞(TC)系由从患者4259切除的异种移植的肿瘤碎片建立，然后通过免疫受损的小鼠连续传代(TC#4259)。将TC#4259与表达模拟物(无TCR)或p53-Y220C-特异性TCR(4259-F6-TCR)的T细胞(105)在37℃下共培养过夜。将单独的TC#4259细胞或者将TC#4259细胞与W6/32泛-HLA I类特异性阻断抗体、IVA12泛-HLA II类特异性阻断抗体或经突变的p53-Y220C肽RNTFRHSVVVPCE(SEQ ID NO:534)在37℃下孵育2小时。将抗体以5μg/mL的终浓度保存在共培养物中。将肽以10μg/mL孵育，并且孵育后洗涤过量肽。单独的培养基(无TC)及PMA和离子霉素分别为阴性对照和阳性对照。对于淋巴细胞→活细胞(PI阴性)→CD3+(T细胞)设门后，通过流式细胞术评价4-1BB的表达。结果示于图53中。
从患者4259分离的TCR 4259-F6-TCR的序列示于以下。从氨基末端开始，第一加下划线的区域是CDR1α(SEQ ID NO:477)，第二加下划线的区域是CDR2α(SEQ ID NO:478)，第三加下划线的区域是CDR3α(SEQ ID NO:479)，第四加下划线的区域是CDR1β(SEQ ID NO:480)，第五加下划线的区域是CDR2β(SEQ ID NO:481)，和第六加下划线的区域是CDR3β(SEQID NO:482)。粗体区是连接子(SEQ ID NO:26)。从氨基末端开始，第一斜体区是α链恒定区(SEQ ID NO:23)并且第二斜体区是β链恒定区(SEQ ID NO:25)。α链可变区(SEQ ID NO:483)包含从氨基末端开始并且就在α链恒定区开始之前结束的序列。β链可变区(SEQ IDNO:484)包含在连接子之后立即开始并且就在β链恒定区开始之前结束的序列。全长α链(SEQ ID NO:485)包含从氨基末端开始并且就在连接子开始之前结束的序列。全长β链(SEQID NO:486)包含在连接子之后立即开始并且以羧基末端结束的序列。
如下所述鉴定癌症反应性T细胞。如下所述分离TCR。
TCR名称：4259-F6-TCR
P53突变的识别：Y220C
筛选方法：p53“热点”突变通用筛选
共培养以鉴定TCR：共培养4259-F6与p53-Y220C肽，和分选CD4+41BB+T细胞
鉴定TCR的方法：单细胞RT-PCR
所有配对的TCR中的TCR的丰度：81.1％(在44对中观察到36次)
TCR取向：α-β
表达载体：SB转座子
MASLRVLLVILWLQLSWVWSQQKEVEQNSGPLSVPEGAIASLNCTYSDRGSQSFFWYRQYSGKSPELIMFIYSNGDKEDGRFTAQLNKASQYVSLLIRDSQPSDSATYLCAWNSGGSNYKLTFGKGTLLTVNPNIQNPEPAVYQLKDPRSQDSTLCLFTDFDSQINVPKTMESGTFITDKCVLDMKAMDSKSNGAIAWSNQTSFTCQDIFKETNATYPSSDVPCDATLTEKSFETDMNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSSRAKRSGSGATNFSLLKQAGDVEENPGPMHLGLLCCGAFSLLWAGPVNAGVTQTPKFRVLKTGQSMTLLCAQDMNHEYMYWYRQDPGMGLRLIHYSVGEGTTAKGEVPDGYNVSRLKKQNFLLGLESAAPSQTSVYFCASSYSQAWGQPQHFGDGTRLSILEDLRNVTPPKVSLFEPSKAEIANKQKATLVCLARGFFPDHVELSWWVNGKEVHSGVCTDPQAYKESNYSYCLSSRLRVSATFWHNPRNHFRCQVQFHGLSEEDKWPEGSPKPVTQNISAEAWGRADCGITSASYQQGVLSATILYEILLGKATLYAVLVSTLVVMAMVKRKNS(SEQ ID NO:588)
来自患者4259的4259-F6-TCR的统计数据示于下表6中。
表6
Figure BDA0002430898550000391
Figure BDA0002430898550000401
实施例4
该实施例证实了通过在自体T细胞内共培养被诱导表达经突变的p53的自体APC来鉴定患者4127中的抗-突变的p53的T细胞(“p53热点突变通用筛选”)。
如图9-10针对患者4127所述进行实验。将来自患者4127的TIL与同种异体的(DRB3*01:01:01或DRB3*02:02:01)APC共培养，所述APC(1)用由无关、WT p53或经突变的p53序列组成的TMG电穿孔，或(2)用肽媒介物(DMSO)或由WT p53-G245序列或经突变的p53-G245S序列组成的经纯化的(>95％，通过HPLC)25个氨基酸的肽脉冲。在37℃下进行共培养过夜。使用ELISPOT测定评价IFN-γ的分泌。结果示于图9中。
将表达对p53-G245S具有特异性的4127-TCR1的T细胞与同种异体的(DRB3*01:01:01或DRB3*02:02:01)APC共培养，所述APC(1)用由无关、WT p53或经突变的p53序列组成的TMG电穿孔，或(2)用肽媒介物(DMSO)或由WT p53-G245序列或经突变的p53-G245S序列组成的经纯化的(>95％，通过HPLC)25个氨基酸的肽脉冲。在37℃下进行共培养过夜。使用ELISPOT测定评价IFN-γ的分泌。结果示于图10中。
实施例5
通过(i)诱导患者的自体抗原呈递细胞(APC)呈递至少一种突变的p53氨基酸序列；(ii)将患者的自体T细胞与呈递经突变的p53氨基酸序列的自体APC共培养；和(iii)选择(a)与呈递经突变的p53氨基酸序列的自体APC共培养的自体T细胞，来筛选来自27名患者的T细胞。表7提供了使用筛选方法进行的T细胞对p53“热点”突变的响应的概述。
表7
Figure BDA0002430898550000411
实施例6
该实施例证实了通过在自体T细胞内共培养被诱导表达经突变的p53的自体APC来鉴定患者4273中的抗-突变的p53 T细胞(“p53热点突变通用筛选”)。该实施例还证实了从患者4273分离两种抗-突变的p53TCR。
如图11-14和33-37针对患者4273所述进行实验。将来自患者4273的TIL片段(F1-F24，n＝24)与用由无关、WT p53或经突变的p53序列组成的TMG电穿孔的自体APC共培养。在37℃下进行共培养过夜。使用ELISPOT测定评价IFN-γ的分泌。结果示于图11中。对于淋巴细胞→活细胞(PI阴性)→CD3+(T细胞)设门后，通过流式细胞术评价4-1BB的表达。结果示于图12中。
将来自患者4273的TIL片段(F1-F24，n＝24)与用肽媒介物(DMSO)或由WT p53-R248序列或经突变的p53-R248W序列组成的经纯化的(>95％，通过HPLC)25-个氨基酸的肽脉冲的自体APC共培养。在37℃下进行共培养过夜。使用ELISPOT测定评价IFN-γ的分泌。结果示于图13中。对于淋巴细胞→活细胞(PI阴性)→CD3+(T细胞)设门后，通过流式细胞术评价4-1BB的表达。结果示于图14中。
对于患者4273，F15是最有反应性的片段，并且F15对LP和TMG的反应相当并且主要由CD4 T细胞进行。因此，将4273-F15与用R248W LP脉冲的APC共培养，并在第二天我们将CD4+41BB+T细胞作为单细胞分选至96孔PCR板的孔中，每孔一个细胞。PCR板在每个孔中都有RT-PCR溶液，其在同一溶液中扩增TCRα和βCDR3区。然后将板的孔分至两个96孔PCR板中，并进行第二轮PCR以分开的反应来扩增CDR3α或CDR3β。通过Sanger测序对每个孔的PCR产物(总共192种PCR产物，对应至每个孔–α或β)进行测序。将核苷酸序列输入IMGT/V-QUEST(imgt.org/IMGT_vquest/vquest？livret＝0&Option＝humanTcR)、IgBlast(ncbi.nlm.nih.gov/igblast/igblast.cgi？CMD＝Web&SEARCH_TYPE＝TCR&L INK_LOC＝igtab)，并由Expasy(web.expasy.org/translate/)翻译。确定可变家族并将其融合至来自经翻译的序列的CDR3和接合点(J或DJ)。可变序列融合至鼠恒定序列，并且重构的TCRα和TCRβ通过弗林蛋白酶-柔性-P2A(RAKR-SGSG-ATNFSLLKQAGDVEENPGP)(SEQ ID NO:26)连接。然后将该序列从头合成为DNA，并克隆至表达载体(γ逆转录病毒或SLEEPING BEAUTY(SB)转座子(University of Minnesota,Minneapolis,MN))中。然后使用标准病毒转导或非病毒转座方案使T细胞表达TCR，并针对推定的肽测试表达鼠源化TCR的T细胞(如通过小鼠TCRβ恒定链检测)。
用编码无关突变、WT p53序列或经突变的p53序列(包括p53-R248W)的TMG转染自体APC。单独的培养基及PMA和离子霉素分别为阴性对照和阳性对照。将来自患者4273的TIL(片段培养物8和15)与TMG转染的APC在37℃下共培养过夜。对于淋巴细胞→活细胞(PI阴性)→CD3+(T细胞)设门后，通过流式细胞术评价4-1BB的表达。结果示于图33中。
将自体APC在37℃下用对应于WT或经突变的p53-R248W新表位的25个氨基酸的肽脉冲2小时。将来自患者4273的对p53-R248W具有特异性的TIL(片段培养物15)与肽-脉冲的APC在37℃下共培养过夜。DMSO是肽媒介物。对于淋巴细胞→活细胞(PI阴性)→CD3+(T细胞)，设门后，通过流式细胞术评价4-1BB的表达。结果示于图34中。
将自体APC用来自p53-R248W新表位的重叠14个氨基酸的15个氨基酸的肽脉冲。将来自患者4273的对p53-R248W具有特异性的TIL与肽-脉冲的APC在37℃下共培养过夜。DMSO是肽媒介物，单独的培养基(仅T细胞)及PMA和离子霉素是对照。25个氨基酸的肽(wt p53-R248和经突变的p53-R248W)是15个氨基酸的肽的另外对照。对于淋巴细胞→活细胞(PI阴性)→CD3+(T细胞)→CD4+CD8-设门后，通过流式细胞术评价4-1BB的表达。结果示于图35中。
将Cos7细胞(每孔2.5x104个)涂铺在平底96孔板的孔上。第二天，将细胞分别与来自患者4273的单独的HLA等位基因以及有或无p53-R248W新抗原的WT或经突变的TP53 TMG共转染。第二天，将来自患者4273的对p53-R248W具有特异性的TIL(片段培养物15)与转染的Cos7细胞在37℃下共培养过夜。通过ELISA评价IFN-γ的分泌。结果示于图36中。
将表达模拟物(无TCR)或4273-TCR1a2的T细胞与自体APC共培养，所述自体APC用肽媒介物(DMSO)或由WT p53-R248序列或经突变的p53-R248W序列组成的经纯化的(>95％，通过HPLC)25个氨基酸的肽脉冲。单独的培养基及PMA和离子霉素分别为阴性对照和阳性对照。在37℃下进行共培养过夜。通过ELISPOT评价IFN-γ的分泌。结果示于图37中。
从患者4273分离的TCR 4273-TP53-R248W-TCR1a1的序列示于下文。从氨基末端开始，第一加下划线区是CDR1α(SEQ ID NO:437)，第二加下划线区是CDR2α(SEQ ID NO:438)，第三加下划线区是CDR3α(SEQ ID NO:439)，第四加下划线区是CDR1β(SEQ ID NO:440)，第五加下划线区是CDR2β(SEQ ID NO:441)，和第六加下划线区是CDR3β(SEQ ID NO:442)。粗体区是连接子(SEQ ID NO:26)。从氨基末端开始，第一加斜体区是α链恒定区(SEQ ID NO:23)并且第二加斜体区是β链恒定区(SEQ ID NO:25)。α链可变区(SEQ ID NO:443)包含从氨基末端开始并且就在α链恒定区开始之前结束的序列。β链可变区(SEQ ID NO:444)包含在连接子之后立即开始并且就在β链恒定区开始之前结束的序列。全长α链(SEQ ID NO:445)包含从氨基末端开始并且就在连接子开始之前结束的序列。全长β链(SEQ ID NO:446)包含在连接子之后立即开始并且以羧基末端结束的序列。
TCR名称：4273-TP53-R248W-TCR1a1
P53突变的识别：R248W
方法：p53“热点”突变通用筛选
MASLRVLLVILWLQLSWVWSQQKEVEQNSGPLSVPEGAIASLNCTYSDRGSQSFFWYRQYSGKSPELIMFIYSNGDKEDGRFTAQLNKASQYVSLLIRDSQPSDSATYLCAVTLCGGYNKLIFGAGTRLAVHPNIQNPEPAVYQLKDPRSQDSTLCLFTDFDSQINVPKTMESGTFITDKCVLDMKAMDSKSNGAIAWSNQTSFTCQDIFKETNATYPSSDVPCDATLTEKSFETDMNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSSRAKRSGSGATNFSLLKQAGDVEENPGPMHNQVLCCVVLCFLGANTVDGGITQSPKYLFRKEGQNVTLSCEQNLNHDAMYWYRQDPGQGLRLIYYSQIVNDFQKGDIVEGYSVSREKKESFPLTVTSAQKNPTAFYLCASSSRDYEQYFGPGTRLTVTEDLRNVTPPKVSLFEPSKAEIANKQKATLVCLARGFFPDHVELSWWVNGKEVHSGVCTDPQAYKESNYSYCLSSRLRVSATFWHNPRNHFRCQVQFHGLSEEDKWPEGSPKPVTQNISAEAWGRADCGITSASYQQGVLSATILYEILLGKATLYAVLVSTLVVMAMVKRKNS(SEQ ID NO:563)
从患者4273分离的TCR 4273-TP53-R248W-TCR1a2的序列示于下文。从氨基末端开始，第一加下划线区是CDR1α(SEQ ID NO:447)，第二加下划线区是CDR2α(SEQ ID NO:448)，第三加下划线区是CDR3α(SEQ ID NO:449)，第四加下划线区是CDR1β(SEQ ID NO:450)，第五加下划线区是CDR2β(SEQ ID NO:451)，和第六加下划线区是CDR3β(SEQ ID NO:452)。粗体区是连接子(SEQ ID NO:26)。从氨基末端开始，第一加斜体区是α链恒定区(SEQ ID NO:23)并且第二加斜体区是β链恒定区(SEQ ID NO:25)。α链可变区(SEQ ID NO:453)包含从氨基末端开始并且就在α链恒定区的开始之前结束的序列。β链可变区(SEQ ID NO:454)包含在连接子之后立即开始并且就在β链恒定区开始之前结束的序列。全长α链(SEQ ID NO:455)包含从氨基末端开始并且就在连接子开始之前结束的序列。全长β链(SEQ ID NO:456)包含在连接子之后立即开始并且以羧基末端结束的序列。
TCR名称：4273-TP53-R248W-TCR1a2
P53突变的识别：R248W
方法：p53“热点”突变通用筛选
MASLRVLLVILWLQLSWVWSQQKEVEQNSGPLSVPEGAIASLNCTYSDRGSQSFFWYRQYSGKSPELIMFIYSNGDKEDGRFTAQLNKASQYVSLLIRDSQPSDSATYLCAVTLSGGYNKLIFGAGTRLAVHPNIQNPEPAVYQLKDPRSQDSTLCLFTDFDSQINVPKTMESGTFITDKCVLDMKAMDSKSNGAIAWSNQTSFTCQDIFKETNATYPSSDVPCDATLTEKSFETDMNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSSRAKRSGSGATNFSLLKQAGDVEENPGPMHNQVLCCVVLCFLGANTVDGGITQSPKYLFRKEGQNVTLSCEQNLNHDAMYWYRQDPGQGLRLIYYSQIVNDFQKGDIVEGYSVSREKKESFPLTVTSAQKNPTAFYLCASSSRDYEQYFGPGTRLTVTEDLRNVTPPKVSLFEPSKAEIANKQKATLVCLARGFFPDHVELSWWVNGKEVHSGVCTDPQAYKESNYSYCLSSRLRVSATFWHNPRNHFRCQVQFHGLSEEDKWPEGSPKPVTQNISAEAWGRADCGITSASYQQGVLSATILYEILLGKATLYAVLVSTLVVMAMVKRKNS(SEQ ID NO:564)
下表8列出了患者4273的TCR的统计数据。在表8中，与经突变的p53蛋白(TMG或肽)共培养后，总有96个孔用41BB+T细胞分选。77个孔具有生产对(意指具有(1)序列和(2)该序列中没有终止密码子)，配对频率为80.2％。那些对中有43个是CDR3A/CDR3B组合，以构成4273-TP53-R248W-TCR1a1(生产对的55.8％)。那些对中有30个是CDR3A/CDR3B组合，以构成4273-TP53-R248W-TCR1a2(生产对的39％)。总体而言，在96个孔中，分别发现了4273-TP53-R248W-TCR1a1的CDR3A和CDR3B 50次和83次。总体而言，在96个孔中，分别发现了4273-TP53-R248W-TCR1a2的CDR3A和CDR3B 33次和83次。
表8
Figure BDA0002430898550000461
实施例7
该实施例证实了在患者4149中抗-突变的p53 T细胞的鉴定。该实施例还证实了从患者4149中分离出一种抗-突变的p53 TCR。
如图15-18针对患者4149所述进行实验。使用Tran方法发现了TCR。然后使用TCR来验证“p53热点突变通用筛选”方法。
将TCR(4149-TCRa2b1或4149-TCRa2b2)转座至来自患者4149的自体PBL中，并与自体APC共培养，所述自体APC(1)用由无关、WT p53或经突变的p53序列组成的TMG电穿孔，或(2)用肽媒介物(DMSO)或由WT p53-Y220序列或经突变的p53-Y220C序列组成的经纯化的(>95％，通过HPLC)25-个氨基酸的肽脉冲。PMA和离子霉素的组合是阳性对照。在37℃下进行共培养过夜。使用ELISPOT测定评价IFN-γ的分泌。结果示于图15中。对于淋巴细胞→活细胞(PI阴性)→CD3+(T细胞)→CD4+mTCR+(TCR转座的T细胞)设门后，通过流式细胞术评价4-1BB的表达。结果示于图16中。
还进行了通过TCRAD深度测序和TCRB深度测序确定CD4+4-1BB+细胞的百分比。结果示于表9中。
表9
Figure BDA0002430898550000471
被4149-F11识别的假定p53Y220C最小表位的作图：将自体DC细胞经肽脉冲(10μg/mL)并在粒细胞-巨噬细胞菌落刺激因子(GM-CSF)和IL-4中静置过夜。将TIL在500CU/mLIL-2中静置2-3天。将2x104个TIL和105个靶细胞在37℃下共培养过夜。通过ELISPOT测量IFN-γ。结果示于表10中。通过FACS用门淋巴细胞\PI(neg)CD3+\CD3+CD4+测量4-1BB表达。结果示于图17中。
表10
Figure BDA0002430898550000472
Figure BDA0002430898550000481
将Cos7细胞(每孔2.5x104个)涂铺在平底96孔板的孔上。20小时后，将细胞与单独的HLA等位基因在有或无TMG的情况下下共转染。20小时后，将自体DC细胞用TMG平行转染。将所有HLA II类等位基因在有或无TMG的情况下共转染一组孔中。将未用TMG转染的细胞在37℃下用10μg/mL的p53-Y220C 15-聚体肽脉冲2-3小时。洗涤后，将在第二REP的第14天的4149-TCRa2b2-转座的T细胞(105)添加至孔，并在37℃下共培养过夜。通过ELISA测量IFN-γ分泌。结果示于表18中。通过NetMHCIIpan进行预测(表11)：cbs.dtu.dk/services/NetMHCIIpan/。
表11
Figure BDA0002430898550000482
在NCI HLA数据库中的3719名DRB_型患者中有1367名(37％)以及在NCI-SB的9名子宫内膜癌和卵巢癌患者中有5名(56％)检测到DRB3*02表达。DRB3*02等位基因的报道频率非常高。
从患者4149分离的TCR 4149TCRa2b2的序列示于下文。从氨基末端开始，第一加下划线区是CDR1α(SEQ ID NO:57)，第二加下划线区是CDR2α(SEQ ID NO:58)，第三加下划线区是CDR3α(SEQ ID NO:59)，第四加下划线区是CDR1β(SEQ ID NO:60)，第五加下划线区是CDR2β(SEQ ID NO:61)，和第六加下划线区是CDR3β(SEQ ID NO:62)。粗体区是连接子(SEQID NO:26)。从氨基末端开始，第一加斜体区是α链恒定区(SEQ ID NO:23)并且第二加斜体区是β链恒定区(SEQ ID NO:25)。α链可变区(SEQ ID NO:63)包含从氨基末端开始并且就在α链恒定区的开始之前结束的序列。β链可变区(SEQ ID NO:64)包含在连接子之后立即开始并且就在β链恒定区开始之前结束的序列。全长α链(SEQ ID NO:65)包含从氨基末端开始并且就在连接子开始之前结束的序列。全长β链(SEQ ID NO:66)包含在连接子之后立即开始并且以羧基末端结束的序列。
癌症反应性T细胞使用下面列出的筛选方法进行鉴定。该患者的p53反应性细胞通过美国申请2017/0224800描述的方法(“Tran方法”)来鉴定。
TCR名称：4149TCRa2b2
P53突变的识别：Y220C
筛选方法：用于验证p53“热点”突变通用筛选(后者是给定的)
共培养以鉴定TCR：共培养4149-F11 TIL片段与p53-Y220C长肽，分选CD4+41BB+T细胞
鉴定TCR的方法：频率配对.将CD4+41BB+分选的T细胞在REP中扩增并使所得的T细胞培养物经受Adaptive Biotechnologies的TCRAD(α)和TCRB(β)深度测序。在4种总TCR矩阵中，I使前两种TCRα与前两种TCRβ配对。第二TCRα和第二TCRβ是反应性TCR，因此TCRa2b2命名。
所有TCR中TCR的丰度：如下
TCR取向：α-β
表达载体：SB转座子
MASAPISMLAMLFTLSGLRAQSVAQPEDQVNVAEGNPLTVKCTYSVSGNPYLFWYVQYPNRGLQFLLKYITGDNLVKGSYGFEAEFNKSQTSFHLKKPSALVSDSALYFCAVRVWDYKLSFGAGTTVTVRANIQNPEPAVYQLKDPRSQDSTLCLFTDFDSQINVPKTMESGTFITDKCVLDMKAMDSKSNGAIAWSNQTSFTCQDIFKETNATYPSSDVPCDATLTEKSFETDMNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSSRAKRSGSGATNFSLLKQAGDVEENPGPMHNQVLCCVVLCFLGANTVDGGITQSPKYLFRKEGQNVTLSCEQNLNHDAMYWYRQDPGQGLRLIYYSQIVNDFQKGDIAEGYSVSREKKESFPLTVTSAQKNPTAFYLCASSISAGGDGYTFGSGTRLTVVEDLRNVTPPKVSLFEPSKAEIANKQKATLVCLARGFFPDHVELSWWVNGKEVHSGVCTDPQAYKESNYSYCLSSRLRVSATFWHNPRNHFRCQVQFHGLSEEDKWPEGSPKPVTQNISAEAWGRADCGITSASYQQGVLSATILYEILLGKATLYAVLVSTLVVMAMVKRKNS(SEQ ID NO:565)
患者4149的TCR 4149TCRa2b2的统计数据示于下表12中。
表12
Figure BDA0002430898550000501
实施例8
该实施例证实了通过在自体T细胞内共培养被诱导表达突变的p53的自体APC来鉴定患者4213中的抗-突变的p53 T细胞(“p53热点突变通用筛选”)。该实施例还证实了从患者4213分离12种抗-突变的p53 TCR。
如图19-20针对患者4213所述进行实验。
将来自患者4213的TIL片段(F2和F24)与用肽媒介物(DMSO)或由经突变的p53-R248Q序列组成的经纯化的(>95％，通过HPLC)25-个氨基酸的肽脉冲的自体APC共培养。在37℃下进行共培养过夜。对于淋巴细胞→活细胞(PI阴性)→CD3+(T细胞)设门后，通过流式细胞术评价4-1BB的表达。结果示于图19中。将CD8+4-1BB+T细胞分选至96孔板的孔中。使用单细胞RT-PCR鉴定TCR。
CD4+T细胞来自患者4213的外周血淋巴细胞。将CD4+T细胞培养物与用肽媒介物(DMSO)或由经突变的p53-R248Q序列组成的经纯化的(>95％，通过HPLC)25-个氨基酸的肽脉冲的自体APC共培养。在37℃下进行共培养过夜。IFN-γ的分泌通过ELISPOT评价。对于淋巴细胞→活细胞(PI阴性)→CD3+(T细胞)设门后，通过流式细胞术评价4-1BB的表达。结果示于图20中。将CD4+41BB+T细胞分选至96孔板的孔中。使用单细胞RT-PCR鉴定TCR。
从患者4213分离的4213-F2-TCR1的序列示于下文。从氨基末端开始，第一加下划线区是CDR1α(SEQ ID NO:317)，第二加下划线区是CDR2α(SEQ ID NO:318)，第三加下划线区是CDR3α(SEQ ID NO:319)，第四加下划线区是CDR1β(SEQ ID NO:320)，第五加下划线区是CDR2β(SEQ ID NO:321)，和第六加下划线区是CDR3β(SEQ ID NO:322)。粗体区是连接子(SEQ ID NO:26)。从氨基末端开始，第一加斜体区是α链恒定区(SEQ ID NO:23)并且第二加斜体区是β链恒定区(SEQ ID NO:25)。α链可变区(SEQ ID NO:323)包含从氨基末端开始并且就在α链恒定区的开始之前结束的序列。β链可变区(SEQ ID NO:324)包含在连接子之后立即开始并且就在β链恒定区开始之前结束的序列。全长α链(SEQ ID NO:325)包含从氨基末端开始并且就在连接子开始之前结束的序列。全长β链(SEQ ID NO:326)包含在连接子之后立即开始并且以羧基末端结束的序列。
癌症反应性T细胞使用下面列出的筛选方法进行鉴定。用于分离TCR的方法示于下文。
TCR名称：4213-F2-TCR1
P53突变的识别：R248Q
筛选方法：p53“热点”突变通用筛选
共培养以鉴定TCR：共培养4213-F2与R248Q长肽，分选CD8+41BB+T细胞
鉴定TCR的方法：单细胞RT-PCR
所有配对的TCR中的TCR的丰度：8.3％(在24对中观察到2次)
TCR取向：α-β
表达载体：SB转座子
MAMLLGASVLILWLQPDWVNSQQKNDDQQVKQNSPSLSVQEGRISILNCDYTNSMFDYFLWYKKYPAEGPTFLISISSIKDKNEDGRFTVFLNKSAKHLSLHIVPSQPGDSAVYFCAANTGNQFYFGTGTSLTVIPNIQNPEPAVYQLKDPRSQDSTLCLFTDFDSQINVPKTMESGTFITDKCVLDMKAMDSKSNGAIAWSNQTSFTCQDIFKETNATYPSSDVPCDATLTEKSFETDMNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSSRAKRSGSGATNFSLLKQAGDVEENPGPMHTRLLCWAALCLLGAELTEAGVAQSPRYKIIEKRQSVAFWCNPISGHATLYWYQQILGQGPKLLIQFQNNG VVDDSQLPKDRFSAERLKGVDSTLKIQPAKLEDSAVYLCASSHLAGEFYNEQFFGPGTRLTVLEDLRNVTPPKVSLFEPSKAEIANKQKATLVCLARGFFPDHVELSWWVNGKEVHSGVCTDPQAYKESNYSYCLSSRLRVSATFWHNPRNHFRCQVQFHGLSEEDKWPEGSPKPVTQNISAEAWGRADCGITSASYQQGVLSATILYEILLGKATLYAVLVSTLVVMAMVKRKNS(SEQ ID NO:566)
患者4213的TCR 4213-F2-TCR1的统计数据示于下表13中。
表13
Figure BDA0002430898550000521
Figure BDA0002430898550000531
从患者4213分离的4213-F2-TCR2的序列示于下文。从氨基末端开始，第一加下划线区是CDR1α(SEQ ID NO:327)，第二加下划线区是CDR2α(SEQ ID NO:328)，第三加下划线区是CDR3α(SEQ ID NO:329)，第四加下划线区是CDR1β(SEQ ID NO:330)，第五加下划线区是CDR2β(SEQ ID NO:331)，和第六加下划线区是CDR3β(SEQ ID NO:332)。粗体区是连接子(SEQ ID NO:26)。从氨基末端开始，第一加斜体区是α链恒定区(SEQ ID NO:23)并且第二加斜体区是β链恒定区(SEQ ID NO:25)。α链可变区(SEQ ID NO:333)包含从氨基末端开始并且就在α链恒定区的开始之前结束的序列。β链可变区(SEQ ID NO:334)包含在连接子之后立即开始并且就在β链恒定区开始之前结束的序列。全长α链(SEQ ID NO:335)包含从氨基末端开始并且就在连接子开始之前结束的序列。全长β链(SEQ ID NO:336)包含在连接子之后立即开始并且以羧基末端结束的序列。
癌症反应性T细胞使用下面列出的筛选方法进行鉴定。用于分离TCR的方法示于下文。
TCR名称：4213-F2-TCR2
P53突变的识别：R248Q
筛选方法：p53“热点”突变通用筛选
共培养以鉴定TCR：共培养4213-F2与R248Q长肽，分选CD8+41BB+T细胞
鉴定TCR的方法：单细胞RT-PCR
所有配对的TCR中的TCR的丰度：12.5％(在24对中观察到3次)
TCR取向：α-β
表达载体：SB转座子
MAGAFLLYVSMKMGGTAGQSLEQPSEVTAVEGAIVQINCTYQTSGFYGLSWYQQHDGGAPTFLSYNAL DGLEETGRFSSFLSRSDSYGYLLLQELQMKDSASYFCAFAYGQNFVFGPGTRLSVLPNIQNPEPAVYQLKDPRSQDSTLCLFTDFDSQINVPKTMESGTFITDKCVLDMKAMDSKSNGAIAWSNQTSFTCQDIFKETNATYPSSDVPCDATLTEKSFETDMNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSSRAKRSGSGATNFSLLKQAGDVEENPGPMHFRLLCCVAFCLLGAGPVDSGVTQTPKHLITATGQRVTLRCSPRSGDLSVYWYQQSLDQGLQFLIQYYNGEERAKGNILERFSAQQFPDLHSELNLSSLELGDSALYFCASSPLGDSGNTIYFGEGSWLTVVEDLRNVTPPKVSLFEPSKAEIANKQKATLVCLARGFFPDHVELSWWVNGKEVHSGVCTDPQAYKESNYSYCLSSRLRVSATFWHNPRNHFRCQVQFHGLSEEDKWPEGSPKPVTQNISAEAWGRADCGITSASYQQGVLSATILYEILLGKATLYAVLVSTLVVMAMVKRKNS(SEQID NO:567)
患者4213的TCR 4213-F2-TCR2的统计数据示于下表14中。
表14
参数 # 频率
总孔 96 100％
CDR3α 4 4.2％
CDR3β 4 4.2％
4213-F2-TCR2对 3 3.1％
总配对的TCR 24 25.0％
从患者4213分离的4213-F2-TCR3的序列示于下文。从氨基末端开始，第一加下划线区是CDR1α(SEQ ID NO:337)，第二加下划线区是CDR2α(SEQ ID NO:338)，第三加下划线区是CDR3α(SEQ ID NO:339)，第四加下划线区是CDR1β(SEQ ID NO:340)，第五加下划线区是CDR2β(SEQ ID NO:341)，并且第六加下划线区是CDR3β(SEQ ID NO:342)。粗体区是连接子(SEQ ID NO:26)。从氨基末端开始，第一加斜体区是α链恒定区(SEQ ID NO:23)并且第二加斜体区是β链恒定区(SEQ ID NO:25)。α链可变区(SEQ ID NO:343)包含从氨基末端开始并且就在α链恒定区的开始之前结束的序列。β链可变区(SEQ ID NO:344)包含在连接子之后立即开始并且就在β链恒定区开始之前结束的序列。全长α链(SEQ ID NO:345)包含从氨基末端开始并且就在连接子开始之前结束的序列。全长β链(SEQ ID NO:346)包含在连接子之后立即开始并且以羧基末端结束的序列。
癌症反应性T细胞使用下面列出的筛选方法进行鉴定。用于分离TCR的方法示于下文。
TCR名称：4213-F2-TCR3
P53突变的识别：R248Q
筛选方法：p53“热点”突变通用筛选
共培养以鉴定TCR：共培养4213-F2与R248Q长肽，分选CD8+41BB+T细胞
鉴定TCR的方法：单细胞RT-PCR
所有配对的TCR中的TCR的丰度：70.8％(在24对中观察到17次)
TCR取向：α-β
表达载体：SB转座子
MATLLGVSLVILWLQLARVNSQQGEEDPQALSIQEGENATMNCSYKTSINNLQWYRQNSGRGLVHLILIRSNEREKHSGRLRVTLDTSKKSSSLLITASRAADTASYFCATDAWNNDMRFGAGTRLTVKPNIQNPEPAVYQLKDPRSQDSTLCLFTDFDSQINVPKTMESGTFITDKCVLDMKAMDSKSNGAIAWSNQTSFTCQDIFKETNATYPSSDVPCDATLTEKSFETDMNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSSRAKRSGSGATNFSLLKQAGDVEENPGPMHIGLLCCVAFSLLWASPVNAGVTQTPKFQVLKTGQSMTLQCAQDMNHNSMYWYRQDPGMGLRLIYYSASEGTTDKGEVPNGYNVSRLNKREFSLRLESAAPSQTSVYFCASSESQGNTEAFFGQGTRLTVVEDLRNVTPPKVSLFEPSKAEIANKQKATLVCLARGFFPDHVELSWWVNGKEVHSGVCTDPQAYKESNYSYCLSSRLRVSATFWHNPRNHFRCQVQFHGLSEEDKWPEGSPKPVTQNISAEAWGRADCGITSASYQQGVLSATILYEILLGKATLYAVLVSTLVVMAMVKRKNS(SEQ ID NO:568)
患者4213的TCR 4213-F2-TCR3的统计数据示于下表15中。
表15
参数 # 频率
总孔 96 100％
CDR3α 19 19.8％
CDR3β 42 43.8％
4213-F2-TCR3对 17 17.7％
总配对的TCR 24 25.0％
从患者4213分离的4213-F24-TCRa1的序列示于下文。从氨基末端开始，第一加下划线区是CDR1α(SEQ ID NO:347)，第二加下划线区是CDR2α(SEQ ID NO:348)，第三加下划线区是CDR3α(SEQ ID NO:349)，第四加下划线区是CDR1β(SEQ ID NO:350)，第五加下划线区是CDR2β(SEQ ID NO:351)，和第六加下划线区是CDR3β(SEQ ID NO:352)。粗体区是连接子(SEQ ID NO:26)。从氨基末端开始，第一加斜体区是α链恒定区(SEQ ID NO:23)并且第二加斜体区是β链恒定区(SEQ ID NO:25)。α链可变区(SEQ ID NO:353)包含从氨基末端开始并且就在α链恒定区的开始之前结束的序列。β链可变区(SEQ ID NO:354)包含在连接子之后立即开始并且就在β链恒定区开始之前结束的序列。全长α链(SEQ ID NO:355)包含从氨基末端开始并且就在连接子开始之前结束的序列。全长β链(SEQ ID NO:356)包含在连接子之后立即开始并且以羧基末端结束的序列。
癌症反应性T细胞使用下面列出的筛选方法进行鉴定。用于分离TCR的方法示于下文。
TCR名称：4213-F24-TCRa1
P53突变的识别：R248Q
筛选方法：p53“热点”突变通用筛选
共培养以鉴定TCR：共培养4213-F24与R248Q长肽，分选CD8+41BB+T细胞
鉴定TCR的方法：单细胞RT-PCR
所有配对的TCR中的TCR的丰度：15.9％(在44对中观察到7次)
TCR取向：α-β
表达载体：SB转座子
MAKHLTTFLVILWLYFYRGNGKNQVEQSPQSLIILEGKNCTLQCNYTVSPFSNLRWYKQDTGRGPVSLTIMTFSENTKSNGRYTATLDADTKQSSLHITASQLSDSASYICVVSSYKIIFGTGTRLHVFPNIQNPEPAVYQLKDPRSQDSTLCLFTDFDSQINVPKTMESGTFITDKCVLDMKAMDSKSNGAIAWSNQTSFTCQDIFKETNATYPSSDVPCDATLTEKSFETDMNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSSRAKRSGSGATNFSLLKQAGDVEENPGPMHTRLLFWVAFCLLGAYHTGAGVSQSPSNKVTEKGKDVELRCDPISGHTALYWYRQRLGQGLEFLIYFQGNSAPDKSGLPSDRFSAERTGESVSTLTIQRTQQEDSAVYLCASSPIQGENSPLHFGNGTRLTVTEDLRNVTPPKVSLFEPSKAEIANKQKATLVCLARGFFPDHVELSWWVNGKEVHSGVCTDPQAYKESNYSYCLSSRLRVSATFWHNPRNHFRCQVQFHGLSEEDKWPEGSPKPVTQNISAEAWGRADCGITSASYQQGVLSATILYEILLGKATLYAVLVSTLVVMAMVKRKNS(SEQ ID NO:569)
患者4213的TCR 4213-F24-TCRa1的统计数据示于下表16中。
表16
参数 # 频率
总孔 96 100％
CDR3α 7 7.3％
CDR3β 80 83.3％
4213-F24-TCRa1对 7 7.3％
总配对的TCR 44 45.8％
从患者4213分离的4213-F24-TCRa2的序列示于下文。从氨基末端开始，第一加下划线区是CDR1α(SEQ ID NO:357)，第二加下划线区是CDR2α(SEQ ID NO:358)，第三加下划线区是CDR3α(SEQ ID NO:359)，第四加下划线区是CDR1β(SEQ ID NO:360)，第五加下划线区是CDR2β(SEQ ID NO:361)，和第六加下划线区是CDR3β(SEQ ID NO:362)。粗体区是连接子(SEQ ID NO:26)。从氨基末端开始，第一加斜体区是α链恒定区(SEQ ID NO:23)并且第二加斜体区是β链恒定区(SEQ ID NO:25)。α链可变区(SEQ ID NO:363)包含从氨基末端开始并且就在α链恒定区开始之前结束的序列。β链可变区(SEQ ID NO:364)包含在连接子之后立即开始并且就在β链恒定区开始之前结束的序列。全长α链(SEQ ID NO:365)包含从氨基末端开始并且就在连接子开始之前结束的序列。全长β链(SEQ ID NO:366)包含在连接子之后立即开始并且以羧基末端结束的序列。
癌症反应性T细胞使用下面列出的筛选方法进行鉴定。用于分离TCR的方法示于下文。
TCR名称：4213-F24-TCRa2
P53突变的识别：R248Q
筛选方法：p53“热点”突变通用筛选
共培养以鉴定TCR：共培养4213-F24与R248Q长肽，分选CD8+41BB+T细胞
鉴定TCR的方法：单细胞RT-PCR
所有配对的TCR中的TCR的丰度：84.1％(在44对中观察到37次)
TCR取向：α-β
表达载体：SB转座子
MAKHLTTFLVILWLYFYRGNGKNQVEQSPQSLIILEGKNCTLQCNYTVSPFSNLRWYKQDTGRGPVSLTIMTFSENTKSNGRYTATLDADTKQSSLHITASQLSDSASYICVVSSYKLIFGTGTRLQVFPNIQNPEPAVYQLKDPRSQDSTLCLFTDFDSQINVPKTMESGTFITDKCVLDMKAMDSKSNGAIAWSNQTSFTCQDIFKETNATYPSSDVPCDATLTEKSFETDMNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSSRAKRSGSGATNFSLLKQAGDVEENPGPMHTRLLFWVAFCLLGAYHTGAGVSQSPSNKVTEKGKDVELRCDPISGHTALYWYRQRLGQGLEFLIYFQGNSAPDKSGLPSDRFSAERTGESVSTLTIQRTQQEDSAVYLCASSPIQGENSPLHFGNGTRLTVTEDLRNVTPPKVSLFEPSKAEIANKQKATLVCLARGFFPDHVELSWWVNGKEVHSGVCTDPQAYKESNYSYCLSSRLRVSATFWHNPRNHFRCQVQFHGLSEEDKWPEGSPKPVTQNISAEAWGRADCGITSASYQQGVLSATILYEILLGKATLYAVLVSTLVVMAMVKRKNS(SEQ ID NO:570)
患者4213的TCR 4213-F24-TCRa2的统计数据示于下表17中。
表17
参数 # 频率
总孔 96 100％
CDR3α 39 40.6％
CDR3β 80 83.3％
4213-F24-TCRa2对 37 38.5％
总配对的TCR 44 45.8％
从患者4213分离的4213-PBL-TCR1的序列示于下文。从氨基末端开始，第一加下划线区是CDR1α(SEQ ID NO:367)，第二加下划线区是CDR2α(SEQ ID NO:368)，第三加下划线区是CDR3α(SEQ ID NO:369)，第四加下划线区是CDR1β(SEQ ID NO:370)，第五加下划线区是CDR2β(SEQ ID NO:371)，和第六加下划线区是CDR3β(SEQ ID NO:372)。粗体区是连接子(SEQ ID NO:26)。从氨基末端开始，第一加斜体区是α链恒定区(SEQ ID NO:23)并且第二加斜体区是β链恒定区(SEQ ID NO:25)。α链可变区(SEQ ID NO:373)包含从氨基末端开始并且就在α链恒定区开始之前结束的序列。β链可变区(SEQ ID NO:374)包含在连接子之后立即开始并且就在β链恒定区开始之前结束的序列。全长α链(SEQ ID NO:375)包含从氨基末端开始并且就在连接子开始之前结束的序列。全长β链(SEQ ID NO:376)包含在连接子之后立即开始并且以羧基末端结束的序列。
癌症反应性T细胞使用下面列出的筛选方法进行鉴定。用于分离TCR的方法示于下文。
TCR名称：4213-PBL-TCR1
P53突变的识别：R248Q
筛选方法：p53“热点”突变通用筛选
共培养以鉴定TCR：将在用R248Q长肽体外致敏之后的CD4+记忆T细胞与R248Q长肽共培养，并分选CD4+41BB+T细胞
鉴定TCR的方法：单细胞RT-PCR
所有配对的TCR中的TCR的丰度：9.5％(在63对中观察到6次)
TCR取向：α-β
表达载体：SB转座子
MALLLVPAFQVIFTLGGTRAQSVTQLDSQVPVFEEAPVELRCNYSSSVSVYLFWYVQYPNQGLQLLLKYLSGSTLVESINGFEAEFNKSQTSFHLRKPSVHISDTAEYFCAVSKGTGAQKLVFGQGTRLTINPNIQNPEPAVYQLKDPRSQDSTLCLFTDFDSQINVPKTMESGTFITDKCVLDMKAMDSKSNGAIAWSNQTSFTCQDIFKETNATYPSSDVPCDATLTEKSFETDMNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSSRAKRSGSGATNFSLLKQAGDVEENPGPMHNQVLCCVVLCFLGANTVDGGITQSPKYLFRKEGQNVTLSCEQNLNHDAMYWYRQDPGQGLRLIYYSQIVNDFQKGDIAEGYSVSREKKESFPLIVTSAQKNPTASYLCASEAFFGQGTRLTVVEDLRNVTPPKVSLFEPSKAEIANKQKATLVCLARGFFPDHVELSWWVNGKEVHSGVCTDPQAYKESNYSYCLSSRLRVSATFWHNPRNHFRCQVQFHGLSEEDKWPEGSPKPVTQNISAEAWGRADCGITSASYQQGVLSATILYEILLGKATLYAVLVSTLVVMAMVKRKNS(SEQID NO:571)
患者4213的TCR 4213-PBL-TCR1的统计数据示于下表18中。
表18
Figure BDA0002430898550000601
Figure BDA0002430898550000611
从患者4213分离的4213-PBL-TCR2的序列示于下文。从氨基末端开始，第一加下划线区是CDR1α(SEQ ID NO:377)，第二加下划线区是CDR2α(SEQ ID NO:378)，第三加下划线区是CDR3α(SEQ ID NO:379)，第四加下划线区是CDR1β(SEQ ID NO:380)，第五加下划线区是CDR2β(SEQ ID NO:381)，和第六加下划线区是CDR3β(SEQ ID NO:382)。粗体区是连接子(SEQ ID NO:26)。从氨基末端开始，第一加斜体区是α链恒定区(SEQ ID NO:23)并且第二加斜体区是β链恒定区(SEQ ID NO:25)。α链可变区(SEQ ID NO:383)包含从氨基末端开始并且在α链恒定区开始之前结束的序列。β链可变区(SEQ ID NO:384)包含在连接子之后立即开始并且就在β链恒定区开始之前结束的序列。全长α链(SEQ ID NO:385)包含从氨基末端开始并且就在连接子开始之前结束的序列。全长β链(SEQ ID NO:386)包含在连接子之后立即开始并且以羧基末端结束的序列.
癌症反应性T细胞使用下面列出的筛选方法进行鉴定。用于分离TCR的方法示于下文。
TCR名称：4213-PBL-TCR2
P53突变的识别：R248Q
筛选方法：p53“热点”突变通用筛选
共培养以鉴定TCR：将在用R248Q长肽体外致敏之后的CD4+记忆T细胞与R248Q长肽共培养，并分选CD4+41BB+T细胞
鉴定TCR的方法：单细胞RT-PCR
所有配对的TCR中的TCR的丰度：7.9％(在63对中观察到5次)
TCR取向：α-β
表达载体：SB转座子
MALVTSITVLLSLGIMGDAKTTQPNSMESNEEEPVHLPCNHSTISGTDYIHWYRQLPSQGPEYVIHGL TSNVNNRMASLAIAEDRKSSTLILHRATLRDAAVYYCILASGAGSYQLTFGKGTKLSVIPNIQNPEPAVYQLKDPRSQDSTLCLFTDFDSQINVPKTMESGTFITDKCVLDMKAMDSKSNGAIAWSNQTSFTCQDIFKETNATYPSSDVPCDATLTEKSFETDMNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSSRAKRSGSGATNFSLLKQAGDVEENPGPMHCRLLCCVVFCLLQAGPLDTAVSQTPKYLVTQMGNDKSIKCEQNLGHDTMYWYKQDSKKFLKIMFSYNNKELIINETVPNRFSPKSPDKAHLNLHINSLELGDSAVYFCASRTIGYNTEAFFGQGTRLTVVEDLRNVTPPKVSLFEPSKAEIANKQKATLVCLARGFFPDHVELSWWVNGKEVHSGVCTDPQAYKESNYSYCLSSRLRVSATFWHNPRNHFRCQVQFHGLSEEDKWPEGSPKPVTQNISAEAWGRADCGITSASYQQGVLSATILYEILLGKATLYAVLVSTLVVMAMVKRKNS(SEQID NO:572)
患者4213的TCR 4213-PBL-TCR2的统计数据示于下表19中。
表19
参数 # 频率
总孔 192 100％
CDR3α 8 4.2％
CDR3β 8 4.2％
4213-PBL-TCR2对 5 2.6％
总配对的TCR 63 32.8％
从患者4213分离的4213-PBL-TCR3的序列示于下文。从氨基末端开始，第一加下划线区是CDR1α(SEQ ID NO:387)，第二加下划线区是CDR2α(SEQ ID NO:388)，第三加下划线区是CDR3α(SEQ ID NO:389)，第四加下划线区是CDR1β(SEQ ID NO:390)，第五加下划线区是CDR2β(SEQ ID NO:391)，和第六加下划线区是CDR3β(SEQ ID NO:392)。粗体区是连接子(SEQ ID NO:26)。从氨基末端开始，第一加斜体区是α链恒定区(SEQ ID NO:23)并且第二加斜体区是β链恒定区(SEQ ID NO:25)。α链可变区(SEQ ID NO:393)包含从氨基末端开始并且就在α链恒定区开始之前结束的序列。β链可变区(SEQ ID NO:394)包含在连接子之后立即开始并且就在β链恒定区开始之前结束的序列。全长α链(SEQ ID NO:395)包含从氨基末端开始并且就在连接子开始之前结束的序列。全长β链(SEQ ID NO:396)包含在连接子之后立即开始并且以羧基末端结束的序列。
癌症反应性T细胞使用下面列出的筛选方法进行鉴定。用于分离TCR的方法示于下文。
TCR名称：4213-PBL-TCR3
P53突变的识别：R248Q
筛选方法：p53“热点”突变通用筛选
共培养以鉴定TCR：将在用R248Q长肽体外致敏之后的CD4+记忆T细胞与R248Q长肽共培养，并分选CD4+41BB+T细胞
鉴定TCR的方法：单细胞RT-PCR
所有配对的TCR中的TCR的丰度：6.3％(在63对中观察到4次)
TCR取向：α-β
表达载体：SB转座子
MAKIRQFLLAILWLQLSCVSAAKNEVEQSPQNLTAQEGEFITINCSYSVGISALHWLQQHPGGGIVSLFMLSSGKKKHGRLIATINIQEKHSSLHITASHPRDSAVYICAALSYNTDKLIFGTGTRLQVFPNIQNPEPAVYQLKDPRSQDSTLCLFTDFDSQINVPKTMESGTFITDKCVLDMKAMDSKSNGAIAWSNQTSFTCQDIFKETNATYPSSDVPCDATLTEKSFETDMNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSSRAKRSGSGATNFSLLKQAGDVEENPGPMHTRLLCWAALCLLGADHTGAGVSQTPSNKVTEKGKYVELRCDPISGHTALYWYRQSLGQGPEFLIYFQGTGAADDSGLPNDRFFAVRPEGSVSTLKIQRTERGDSAVYLCASSLSGLLQETQYFGPGTRLLVLEDLRNVTPPKVSLFEPSKAEIANKQKATLVCLARGFFPDHVELSWWVNGKEVHSGVCTDPQAYKESNYSYCLSSRLRVSATFWHNPRNHFRCQVQFHGLSEEDKWPEGSPKPVTQNISAEAWGRADCGITSASYQQGVLSATILYEILLGKATLYAVLVSTLVVMAMVKRKNS(SEQ ID NO:573)
患者4213的TCR 4213-PBL-TCR3的统计数据示于下表20中。
表20
参数 # 频率
总孔 192 100％
CDR3α 4 2.1％
CDR3β 7 3.6％
4213-PBL-TCR3对 4 2.1％
总配对的TCR 63 32.8％
从患者4213分离的4213-PBL-TCR4a1的序列示于下文。从氨基末端开始，第一加下划线区是CDR1α(SEQ ID NO:397)，第二加下划线区是CDR2α(SEQ ID NO:398)，第三加下划线区是CDR3α(SEQ ID NO:399)，第四加下划线区是CDR1β(SEQ ID NO:400)，第五加下划线区是CDR2β(SEQ ID NO:401)，和第六加下划线区是CDR3β(SEQ ID NO:402)。粗体区是连接子(SEQ ID NO:26)。从氨基末端开始，第一加斜体区是α链恒定区(SEQ ID NO:23)并且第二加斜体区是β链恒定区(SEQ ID NO:25)。α链可变区(SEQ ID NO:403)包含从氨基末端开始并且就在α链恒定区的开始之前结束的序列。β链可变区(SEQ ID NO:404)包含在连接子之后立即开始并且就在β链恒定区开始之前结束的序列。全长α链(SEQ ID NO:405)包含从氨基末端开始并且就在连接子开始之前结束的序列。全长β链(SEQ ID NO:406)包含在连接子之后立即开始并且以羧基末端结束的序列。
癌症反应性T细胞使用下面列出的筛选方法进行鉴定。用于分离TCR的方法示于下文。
TCR名称：4213-PBL-TCR4a1
P53突变的识别：R248Q
筛选方法：p53“热点”突变通用筛选
共培养以鉴定TCR：将在用R248Q长肽体外致敏之后的CD4+记忆T细胞与R248Q长肽共培养并分选CD4+41BB+T细胞
鉴定TCR的方法：单细胞RT-PCR
所有配对的TCR中的TCR的丰度：3.2％(在63对中观察到2次)
TCR取向：α-β
表达载体：SB转座子
MAYSPGLVSLILLLLGRTRGNSVTQMEGPVTLSEEAFLTINCTYTATGYPSLFWYVQYPGEGLQLLLKATKADDKGSNKGFEATYRKETTSFHLEKGSVQVSDSAVYFCALSHTGSSNTGKLIFGQGTRLQVKPNIQNPEPAVYQLKDPRSQDSTLCLFTDFDSQINVPKTMESGTFITDKCVLDMKAMDSKSNGAIAWSNQTSFTCQDIFKETNATYPSSDVPCDATLTEKSFETDMNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSSRAKRSGSGATNFSLLKQAGDVEENPGPMHTRLLCWAALCLLGAELTEAGVAQSPRYKIIEKRQSVAFWCNPISGHATLYWYQQILGQGPKLLIQFQNNGVVDDSQLPKDRFSAERLKGVDSTLKIQPAKLEDSAVYLCASSTGGGRHQPQHFGDGTRLSILEDLRNVTPPKVSLFEPSKAEIANKQKATLVCLARGFFPDHVELSWWVNGKEVHSGVCTDPQAYKESNYSYCLSSRLRVSATFWHNPRNHFRCQVQFHGLSEEDKWPEGSPKPVTQNISAEAWGRADCGITSASYQQGVLSATILYEILLGKATLYAVLVSTLVVMAMVKRKNS(SEQ ID NO:574)
患者4213的TCR 4213-PBL-TCR4a1的统计数据示于下表21中。
表21
参数 # 频率
总孔 192 100％
CDR3α 2 1.0％
CDR3β 36 18.8％
4213-PBL-TCR4a1对 2 1.0％
总配对的TCR 63 32.8％
从患者4213分离的4213-PBL-TCR4a2的序列示于下文。从氨基末端开始，第一加下划线区是CDR1α(SEQ ID NO:407)，第二加下划线区是CDR2α(SEQ ID NO:408)，第三加下划线区是CDR3α(SEQ ID NO:409)，第四加下划线区是CDR1β(SEQ ID NO:410)，第五加下划线区是CDR2β(SEQ ID NO:411)，和第六加下划线区是CDR3β(SEQ ID NO:412)。粗体区是连接子(SEQ ID NO:26)。从氨基末端开始，第一加斜体区是α链恒定区(SEQ ID NO:23)并且第二加斜体区是β链恒定区(SEQ ID NO:25)。α链可变区(SEQ ID NO:413)包含从氨基末端开始并且就在α链恒定区开始之前结束的序列。β链可变区(SEQ ID NO:414)包含在连接子之后立即开始并且就在β链恒定区开始之前结束的序列。全长α链(SEQ ID NO:415)包含从氨基末端开始并且就在连接子开始之前结束的序列。全长β链(SEQ ID NO:416)包含在连接子之后立即开始并且以羧基末端结束的序列。
癌症反应性T细胞使用下面列出的筛选方法进行鉴定。用于分离TCR的方法示于下文。
TCR名称：4213-PBL-TCR4a2
P53突变的识别：R248Q
筛选方法：p53“热点”突变通用筛选
共培养以鉴定TCR：将在用R248Q长肽体外致敏之后的CD4+记忆T细胞与R248Q长肽共培养并分选CD4+41BB+T细胞
鉴定TCR的方法：单细胞RT-PCR
所有配对的TCR中的TCR的丰度：3.2％(在63对中观察到2次)
TCR取向：α-β
表达载体：SB转座子
MAYSPGLVSLILLLLGRTRGNSVTQMEGPVTLSEEAFLTINCTYTATGYPSLFWYVQYPGEGLQLLLKATKADDKGSNKGFEATYRKETTSFHLEKGSVQVSDSAVYFCALSQTGSSKTGKLIFGQGTRLQVKPNIQNPEPAVYQLKDPRSQDSTLCLFTDFDSQINVPKTMESGTFITDKCVLDMKAMDSKSNGAIAWSNQTSFTCQDIFKETNATYPSSDVPCDATLTEKSFETDMNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSSRAKRSGSGATNFSLLKQAGDVEENPGPMHTRLLCWAALCLLGAELTEAGVAQSPRYKIIEKRQSVAFWCNPISGHATLYWYQQILGQGPKLLIQFQNNGVVDDSQLPKDRFSAERLKGVDSTLKIQPAKLEDSAVYLCASSTGGGRHQPQHFGDGTRLSILEDLRNVTPPKVSLFEPSKAEIANKQKATLVCLARGFFPDHVELSWWVNGKEVHSGVCTDPQAYKESNYSYCLSSRLRVSATFWHNPRNHFRCQVQFHGLSEEDKWPEGSPKPVTQNISAEAWGRADCGITSASYQQGVLSATILYEILLGKATLYAVLVSTLVVMAMVKRKNS(SEQ ID NO:575)
患者4213的TCR 4213-PBL-TCR4a2的统计数据示于下表22中。
表22
参数 # 频率
总孔 192 100％
CDR3α 2 1.0％
CDR3β 36 18.8％
4213-PBL-TCR4a2对 2 1.0％
总配对的TCR 63 32.8％
从患者4213分离的4213-PBL-TCR4a3的序列示于下文。从氨基末端开始，第一加下划线区是CDR1α(SEQ ID NO:417)，第二加下划线区是CDR2α(SEQ ID NO:418)，第三加下划线区是CDR3α(SEQ ID NO:419)，第四加下划线区是CDR1β(SEQ ID NO:420)，第五加下划线区是CDR2β(SEQ ID NO:421)，和第六加下划线区是CDR3β(SEQ ID NO:422)。粗体区是连接子(SEQ ID NO:26)。从氨基末端开始，第一加斜体区是α链恒定区(SEQ ID NO:23)并且第二加斜体区是β链恒定区(SEQ ID NO:25)。α链可变区(SEQ ID NO:423)包含从氨基末端开始并且就在α链恒定区开始之前结束的序列。β链可变区(SEQ ID NO:424)包含在连接子之后立即开始并且就在β链恒定区开始之前结束的序列。全长α链(SEQ ID NO:425)包含从氨基末端开始并且就在连接子开始之前结束的序列。全长β链(SEQ ID NO:426)包含在连接子之后立即开始并且以羧基末端结束的序列。
癌症反应性T细胞使用下面列出的筛选方法进行鉴定。用于分离TCR的方法示于下文。
TCR名称：4213-PBL-TCR4a3
P53突变的识别：R248Q
筛选方法：p53“热点”突变通用筛选
共培养以鉴定TCR：将在用R248Q长肽体外致敏之后的CD4+记忆T细胞与R248Q长肽共培养并分选CD4+41BB+T细胞
鉴定TCR的方法：单细胞RT-PCR
所有配对的TCR中的TCR的丰度：4.8％(在63对中观察到3次)
TCR取向：α-β
表达载体：SB转座子
MAYSPGLVSLILLLLGRTRGNSVTQMEGPVTLSEEAFLTINCTYTATGYPSLFWYVQYPGEGLQLLLKATKADDKGSNKGFEATYRKETTSFHLEKGSVQVSDSAVYFCALSQTGSSNTGKLIFGQGTRLQVKPNIQNPEPAVYQLKDPRSQDSTLCLFTDFDSQINVPKTMESGTFITDKCVLDMKAMDSKSNGAIAWSNQTSFTCQDIFKETNATYPSSDVPCDATLTEKSFETDMNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSSRAKRSGSGATNFSLLKQAGDVEENPGPMHTRLLCWAALCLLGAELTEAGVAQSPRYKIIEKRQSVAFWCNPISGHATLYWYQQILGQGPKLLIQFQNNGVVDDSQLPKDRFSAERLKGVDSTLKIQPAKLEDSAVYLCASSTGGGRHQPQHFGDGTRLSILEDLRNVTPPKVSLFEPSKAEIANKQKATLVCLARGFFPDHVELSWWVNGKEVHSGVCTDPQAYKESNYSYCLSSRLRVSATFWHNPRNHFRCQVQFHGLSEEDKWPEGSPKPVTQNISAEAWGRADCGITSASYQQGVLSATILYEILLGKATLYAVLVSTLVVMAMVKRKNS(SEQ ID NO:576)
患者4213的TCR 4213-PBL-TCR4a3的统计数据示于下表23中。
表23
Figure BDA0002430898550000681
Figure BDA0002430898550000691
从患者4213分离的4213-PBL-TCR4a4的序列示于下文。从氨基末端开始，第一加下划线区是CDR1α(SEQ ID NO:427)，第二加下划线区是CDR2α(SEQ ID NO:428)，第三加下划线区是CDR3α(SEQ ID NO:429)，第四加下划线区是CDR1β(SEQ ID NO:430)，第五加下划线区是CDR2β(SEQ ID NO:431)，和第六加下划线区是CDR3β(SEQ ID NO:432)。粗体区是连接子(SEQ ID NO:26)。从氨基末端开始，第一加斜体区是α链恒定区(SEQ ID NO:23)并且第二加斜体区是β链恒定区(SEQ ID NO:25)。α链可变区(SEQ ID NO:433)包含从氨基末端开始并且就在α链恒定区开始之前结束的序列。β链可变区(SEQ ID NO:434)包含在连接子之后立即开始并且就在β链恒定区开始之前结束的序列。全长α链(SEQ ID NO:435)包含从氨基末端开始并且就在连接子开始之前结束的序列。全长β链(SEQ ID NO:436)包含在连接子之后立即开始并且以羧基末端结束的序列。
癌症反应性T细胞使用下面列出的筛选方法进行鉴定。用于分离TCR的方法示于下文。
TCR名称：4213-PBL-TCR4a4
P53突变的识别：R248Q
筛选方法：p53“热点”突变通用筛选
共培养以鉴定TCR：将在用R248Q长肽体外致敏之后的CD4+记忆T细胞与R248Q长肽共培养并分选CD4+41BB+T细胞
鉴定TCR的方法：单细胞RT-PCR
所有配对的TCR中的TCR的丰度：3.2％(在63对中观察到2次)
TCR取向：α-β
表达载体：SB转座子
MAYSPGLVSLILLLLGRTRGNSVTQMEGPVTLSEEAFLTINCTYTATGYPSLFWYVQYPGEGLQLLLKATKADDKGSNKGFEATYRKETTSFHLEKGSVQVSDSAVYFCALSTTGSSNTGKLIFGQGTTLQVKPNIQNPEPAVYQLKDPRSQDSTLCLFTDFDSQINVPKTMESGTFITDKCVLDMKAMDSKSNGAIAWSNQTSFTCQDIFKETNATYPSSDVPCDATLTEKSFETDMNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSSRAKRSGSGATNFSLLKQAGDVEENPGPMHTRLLCWAALCLLGAELTEAGVAQSPRYKIIEKRQSVAFWCNPISGHATLYWYQQILGQGPKLLIQFQNNGVVDDSQLPKDRFSAERLKGVDSTLKIQPAKLEDSAVYLCASSTGGGRHQPQHFGDGTRLSILEDLRNVTPPKVSLFEPSKAEIANKQKATLVCLARGFFPDHVELSWWVNGKEVHSGVCTDPQAYKESNYSYCLSSRLRVSATFWHNPRNHFRCQVQFHGLSEEDKWPEGSPKPVTQNISAEAWGRADCGITSASYQQGVLSATILYEILLGKATLYAVLVSTLVVMAMVKRKNS(SEQ ID NO:577)
患者4213的TCR 4213-PBL-TCR4a4的统计数据示于下表24中。
表24
参数 # 频率
总孔 192 100％
CDR3α 2 1.0％
CDR3β 36 18.8％
4213-PBL-TCR4a3对 2 1.0％
总配对的TCR 63 32.8％
实施例9
该实施例证实了通过在自体T细胞内共培养被诱导以表达突变的p53的自体APC来鉴定患者4268中的抗-突变的p53 T细胞(“p53热点突变通用筛选”)。该实施例还证实了从患者4268分离五种抗-突变的p53TCR。
如针对患者4268的图21-24所述进行实验。
将来自患者4268的TIL片段(F1-F24，n＝24)与用由无关、WT p53或经突变的p53序列组成的TMG电穿孔的自体APC共培养。在37℃下进行共培养过夜。使用ELISPOT测定评价IFN-γ的分泌。结果示于图21中。
将来自患者4268的TIL片段(F1-F24，n＝24)与用肽媒介物(DMSO)或由WT p53-R248序列或经突变的p53-R248Q序列组成的经纯化的(>95％，通过HPLC)25-个氨基酸的肽脉冲的自体APC共培养。在37℃下进行共培养过夜。使用ELISPOT测定评价IFN-γ的分泌。结果示于图22中。
将来自患者4268的TIL片段(F1-F24，n＝24)与用肽媒介物(DMSO)或由wt p53-R248序列或经突变的p53-R248Q序列组成的经纯化的(>95％，通过HPLC)25-个氨基酸的肽脉冲的自体APC共培养。在37℃下进行共培养过夜。对于淋巴细胞→活细胞(PI阴性)→CD3+(T细胞)设门后，通过流式细胞术评价4-1BB的表达。结果示于23-24中。TIL片段F18和F19是对CD4+41BB+T细胞进行分选后的TCR的来源。TIL片段F7、F8和F15是对CD8+4-1BB+T细胞进行分选后的TCR的来源。
从患者4268分离的4268-TCR1的序列示于下文。从氨基末端开始，第一加下划线区是CDR1α(SEQ ID NO:137)，第二加下划线区是CDR2α(SEQ ID NO:138)，第三加下划线区是CDR3α(SEQ ID NO:139)，第四加下划线区是CDR1β(SEQ ID NO:140)，第五加下划线区是CDR2β(SEQ ID NO:141)，和第六加下划线区是CDR3β(SEQ ID NO:142)。粗体区是连接子(SEQ ID NO:26)。从氨基末端开始，第一加斜体区是α链恒定区(SEQ ID NO:23)并且第二加斜体区是β链恒定区(SEQ ID NO:25)。α链可变区(SEQ ID NO:143)包含从氨基末端开始并且在α链恒定区开始之前就结束的序列。β链可变区(SEQ ID NO:144)包含在连接子之后立即开始并且在β链恒定区开始之前就结束的序列。全长α链(SEQ ID NO:145)包含从氨基末端开始并且在连接子开始之前就结束的序列。全长β链(SEQ ID NO:146)包含在连接子之后立即开始并且以羧基末端结束的序列。
癌症反应性T细胞使用下面列出的筛选方法进行鉴定。用于分离TCR的方法示于下文。
TCR名称：4268-TCR1
P53突变的识别：R248Q
方法：p53“热点”突变通用筛选
共培养以鉴定TCR：共培养4268-F7和4268-F8与p53-R248Q长肽，分选CD8+41BB+T细胞
鉴定TCR的方法：单细胞RT-PCR
所有配对的TCR中的TCR的丰度：78.7％(在61对中观察到48次)
TCR取向：α-β
表达载体：SB转座子
MASLRVLLVILWLQLSWVWSQQKEVEQNSGPLSVPEGAIASLNCTYSDRGSQSFFWYRQYSGKSPELIMFIYSNGDKEDGRFTAQLNKASQYVSLLIRDSQPSDSATYLCAVSWYSTLTFGKGTMLLVSPNIQNPEPAVYQLKDPRSQDSTLCLFTDFDSQINVPKTMESGTFITDKCVLDMKAMDSKSNGAIAWSNQTSFTCQDIFKETNATYPSSDVPCDATLTEKSFETDMNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSSRAKRSGSGATNFSLLKQAGDVEENPGPMHTRLFFYVALCLLWAGHRDAGITQSPRYKITETGRQVTLMCHQTWSHSYMFWYRQDLGHGLRLIYYSAAADITDKGEVPDGYVVSRSKTENFPLTLESATRSQTSVYFCASSGSRTDTQYFGPGTRLTVLEDLRNVTPPKVSLFEPSKAEIANKQKATLVCLARGFFPDHVELSWWVNGKEVHSGVCTDPQAYKESNYSYCLSSRLRVSATFWHNPRNHFRCQVQFHGLSEEDKWPEGSPKPVTQNISAEAWGRADCGITSASYQQGVLSATILYEILLGKATLYAVLVSTLVVMAMVKRKNS(SEQ ID NO:578)
患者4268的TCR 4268-TCR1的统计数据示于下表25中。
表25
Figure BDA0002430898550000721
Figure BDA0002430898550000731
从患者4268分离的4268-TCR2的序列示于下文。从氨基末端开始，第一加下划线区是CDR1α(SEQ ID NO:147)，第二加下划线区是CDR2α(SEQ ID NO:148)，第三加下划线区是CDR3α(SEQ ID NO:149)，第四加下划线区是CDR1β(SEQ ID NO:150)，第五加下划线区是CDR2β(SEQ ID NO:151)，和第六加下划线区是CDR3β(SEQ ID NO:152)。粗体区是连接子(SEQ ID NO:26)。从氨基末端开始，第一加斜体区是α链恒定区(SEQ ID NO:23)并且第二加斜体区是β链恒定区(SEQ ID NO:25)。α链可变区(SEQ ID NO:153)包含从氨基末端开始并且在α链恒定区开始之前就结束的序列。β链可变区(SEQ ID NO:154)包含在连接子之后立即开始并且就β链恒定区开始之前结束的序列。全长α链(SEQ ID NO:155)包含从氨基末端开始并且就在连接子开始之前结束的序列。全长β链(SEQ ID NO:156)包含在连接子之后立即开始并且以羧基末端结束的序列。
癌症反应性T细胞使用下面列出的筛选方法进行鉴定。用于分离TCR的方法示于下文。
TCR名称：4268-TCR2
P53突变的识别：R248Q
方法：p53“热点”突变通用筛选
共培养以鉴定TCR：共培养4268-F7和4268-F8与p53-R248Q长肽，分选CD8+41BB+T细胞
鉴定TCR的方法：单细胞RT-PCR
所有配对的TCR中的TCR的丰度：6.6％(在61对中观察到4次)
TCR取向：α-β
表达载体：SB转座子
MALKFSVSILWIQLAWVSTQLLEQSPQFLSIQEGENLTVYCNSSSVFSSLQWYRQEPGEGPVLLVTVV TGGEVKKLKRLTFQFGDARKDSSLHITAAQPGDTGLYLCAGEFAGNQFYFGTGTSLTVIPNIQNPEPAVYQLKDPRSQDSTLCLFTDFDSQINVPKTMESGTFITDKCVLDMKAMDSKSNGAIAWSNQTSFTCQDIFKETNATYPSSDVPCDATLTEKSFETDMNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSSRAKRSGSGATNFSLLKQAGDVEENPGPMHCRLLCCAVLCLLGAVPIDTEVTQTPKHLVMGMTNKKSLKCEQHMGHRAMYWYKQKAKKPPELMFVYSYEKLSINESVPSRFSPECPNSSLLNLHLHALQPEDSALYLCASSQVGLTYEQYFGPGTRLTVTEDLRNVTPPKVSLFEPSKAEIANKQKATLVCLARGFFPDHVELSWWVNGKEVHSGVCTDPQAYKESNYSYCLSSRLRVSATFWHNPRNHFRCQVQFHGLSEEDKWPEGSPKPVTQNISAEAWGRADCGITSASYQQGVLSATILYEILLGKATLYAVLVSTLVVMAMVKRKNS(SEQID NO:579)
患者4268的TCR 4268-TCR2的统计数据示于下表26中。
表26
参数 # 频率
总孔 96 100％
CDR3α 6 6.3％
CDR3β 4 4.2％
4268-TCR2对 4 4.2％
总配对的TCR 61 63.5％
从患者4268分离的4268-TCR3的序列示于下文。从氨基末端开始，第一加下划线区是CDR1α(SEQ ID NO:157)，第二加下划线区是CDR2α(SEQ ID NO:158)，第三加下划线区是CDR3α(SEQ ID NO:159)，第四加下划线区是CDR1β(SEQ ID NO:160)，第五加下划线区是CDR2β(SEQ ID NO:161)，和第六加下划线区是CDR3β(SEQ ID NO:162)。粗体区是连接子(SEQ ID NO:26)。从氨基末端开始，第一加斜体区是α链恒定区(SEQ ID NO:23)并且第二加斜体区是β链恒定区(SEQ ID NO:25)。α链可变区(SEQ ID NO:163)包含从氨基末端开始并且在α链恒定区开始之前就结束的序列。β链可变区(SEQ ID NO:164)包含在连接子之后立即开始并且就在β链恒定区开始之前结束的序列。全长α链(SEQ ID NO:165)包含从氨基末端开始并且就在连接子开始之前结束的序列。全长β链(SEQ ID NO:166)包含在连接子之后立即开始并且以羧基末端结束的序列。
癌症反应性T细胞使用下面列出的筛选方法进行鉴定。用于分离TCR的方法示于下文。
TCR名称：4268-TCR3
P53突变的识别：R248Q
方法：p53“热点”突变通用筛选
共培养以鉴定TCR：共培养4268-F15与p53-R248Q长肽，分选CD8+41BB+T细胞
鉴定TCR的方法：单细胞RT-PCR
所有配对的TCR中的TCR的丰度：88.6％(在35对中观察到31次)
TCR取向：α-β
表达载体：SB转座子
MASAPISMLAMLFTLSGLRAQSVAQPEDQVNVAEGNPLTVKCTYSVSGNPYLFWYVQYPNRGLQFLLKYITGDNLVKGSYGFEAEFNKSQTSFHLKKPSALVSDSALYFCAVRDNSGGSNYKLTFGKGTLLTVNPNIQNPEPAVYQLKDPRSQDSTLCLFTDFDSQINVPKTMESGTFITDKCVLDMKAMDSKSNGAIAWSNQTSFTCQDIFKETNATYPSSDVPCDATLTEKSFETDMNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSSRAKRSGSGATNFSLLKQAGDVEENPGPMHTRLLCWAALCLLGAELTEAGVAQSPRYKIIEKRQSVAFWCNPISGHATLYWYQQILGQGPKLLIQFQNNGVVDDSQLPKDRFSAERLKGVDSTLKIQPAKLEDSAVYLCASSLGQGQTQYFGPGTRLLVLEDLRNVTPPKVSLFEPSKAEIANKQKATLVCLARGFFPDHVELSWWVNGKEVHSGVCTDPQAYKESNYSYCLSSRLRVSATFWHNPRNHFRCQVQFHGLSEEDKWPEGSPKPVTQNISAEAWGRADCGITSASYQQGVLSATILYEILLGKATLYAVLVSTLVVMAMVKRKNS(SEQ ID NO:580)
患者4268的TCR 4268-TCR3的统计数据示于下表27中。
表27
参数 # 频率
总孔 96 100％
CDR3α 42 43.8％
CDR3β 37 38.5％
4268-TCR3对 31 32.3％
总配对的TCR 35 36.5％
从患者4268分离的4268-TCR4的序列示于下文。从氨基末端开始，第一加下划线区是CDR1α(SEQ ID NO:167)，第二加下划线区是CDR2α(SEQ ID NO:168)，第三加下划线区是CDR3α(SEQ ID NO:169)，第四加下划线区是CDR1β(SEQ ID NO:170)，第五加下划线区是CDR2β(SEQ ID NO:171)，和第六加下划线区是CDR3β(SEQ ID NO:172)。粗体区是连接子(SEQ ID NO:26)。从氨基末端开始，第一加斜体区是α链恒定区(SEQ ID NO:23)并且第二加斜体区是β链恒定区(SEQ ID NO:25)。α链可变区(SEQ ID NO:173)包含从氨基末端开始并且就在α链恒定区开始之前结束的序列。β链可变区(SEQ ID NO:174)包含在连接子之后立即开始并且就在β链恒定区开始之前结束的序列。全长α链(SEQ ID NO:175)包含从氨基末端开始并且在连接子开始之前就结束的序列。全长β链(SEQ ID NO:176)包含在连接子之后立即开始并且以羧基末端结束的序列。
癌症反应性T细胞使用下面列出的筛选方法进行鉴定。用于分离TCR的方法示于下文。
TCR名称：4268-TCR4
P53突变的识别：R248Q
方法：p53“热点”突变通用筛选
共培养以鉴定TCR：共培养4268-F18与p53-R248Q长肽，分选CD4+41BB+T细胞
鉴定TCR的方法：单细胞RT-PCR
所有配对的TCR中的TCR的丰度：95.2％(在42对中观察到40次)
TCR取向：α-β
表达载体：SB转座子
MALLLVPAFQVIFTLGGTRAQSVTQLDSQVPVFEEAPVELRCNYSSSVSVYLFWYVQYPNQGLQLLLKYLSGSTLVESINGFEAEFNKSQTSFHLRKPSVHISDTAEYFCAVRGSSGTYKYIFGTGTRLKVLANIQNPEPAVYQLKDPRSQDSTLCLFTDFDSQINVPKTMESGTFITDKCVLDMKAMDSKSNGAIAWSNQTSFTCQDIFKETNATYPSSDVPCDATLTEKSFETDMNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSSRAKRSGSGATNFSLLKQAGDVEENPGPMHIRLLCRVAFCFLAVGLVDVKVTQSSRYLVKRTGEKVFLECVQDMDHENMFWYRQDPGLGLRLIYFSYDVKMKEKGDIPEGYSVSREKKERFSLILESASTNQTSMYLCASKGDQNTEAFFGQGTRLTVVEDLRNVTPPKVSLFEPSKAEIANKQKATLVCLARGFFPDHVELSWWVNGKEVHSGVCTDPQAYKESNYSYCLSSRLRVSATFWHNPRNHFRCQVQFHGLSEEDKWPEGSPKPVTQNISAEAWGRADCGITSASYQQGVLSATILYEILLGKATLYAVLVSTLVVMAMVKRKNS(SEQ ID NO:581)
患者4268的TCR 4268-TCR4的统计数据示于下表28中。
表28
参数 # 频率
总孔 96 100％
CDR3α 43 44.8％
CDR3β 53 55.2％
4268-TCR4对 40 41.7％
总配对的TCR 42 43.8％
从患者4268分离的4268-TCR5的序列示于下文。从氨基末端开始，第一加下划线区是CDR1α(SEQ ID NO:177)，第二加下划线区是CDR2α(SEQ ID NO:178)，第三加下划线区是CDR3α(SEQ ID NO:179)，第四加下划线区是CDR1β(SEQ ID NO:180)，第五加下划线区是CDR2β(SEQ ID NO:181)，和第六加下划线区是CDR3β(SEQ ID NO:182)。粗体区是连接子(SEQ ID NO:26)。从氨基末端开始，第一加斜体区是α链恒定区(SEQ ID NO:23)并且第二加斜体区是β链恒定区(SEQ ID NO:25)。α链可变区(SEQ ID NO:183)包含从氨基末端开始并且在α链恒定区开始之前就结束的序列。β链可变区(SEQ ID NO:184)包含在连接子之后立即开始并且就在β链恒定区开始之前结束的序列。全长α链(SEQ ID NO:185)包含从氨基末端开始并且就在连接子开始之前结束的序列。全长β链(SEQ ID NO:186)包含在连接子之后立即开始并且以羧基末端结束的序列。
癌症反应性T细胞使用下面列出的筛选方法进行鉴定。用于分离TCR的方法示于下文。
TCR名称：4268-TCR5
P53突变的识别：R248Q
方法：p53“热点”突变通用筛选
共培养以鉴定TCR：共培养4268-F19与p53-mut-TMG，分选CD4+41BB+T细胞
鉴定TCR的方法：单细胞RT-PCR
所有配对的TCR中的TCR的丰度：11.8％(在17对中观察到2次)
TCR取向：α-β
表达载体：SB转座子
MAGVFLLYVSMKMGGTTGQNIDQPTEMTATEGAIVQINCTYQTSGFNGLFWYQQHAGEAPTFLSYNVL DGLEEKGRFSSFLSRSKGYSYLLLKELQMKDSASYLCAVRDLQTGANNLFFGTGTRLTVIPNIQNPEPAVYQLKDPRSQDSTLCLFTDFDSQINVPKTMESGTFITDKCVLDMKAMDSKSNGAIAWSNQTSFTCQDIFKETNATYPSSDVPCDATLTEKSFETDMNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSSRAKRSGSGATNFSLLKQAGDVEENPGPMHIRLLCRVAFCFLAVGLVDVKVTQSSRYLVKRTGEKVFLECVQDMDHENMFWYRQDPGLGLRLIYFSYDVKMKEKGDIPEGYSVSREKKERFSLILESASTNQTSMYLCASSLTFGTTEAFFGQGTRLTVVEDLRNVTPPKVSLFEPSKAEIANKQKATLVCLARGFFPDHVELSWWVNGKEVHSGVCTDPQAYKESNYSYCLSSRLRVSATFWHNPRNHFRCQVQFHGLSEEDKWPEGSPKPVTQNISAEAWGRADCGITSASYQQGVLSATILYEILLGKATLYAVLVSTLVVMAMVKRKNS(SEQ ID NO:582)
患者4268的TCR 4268-TCR5的统计数据示于下表29中。
表29
参数 # 频率
总孔 96 100％
CDR3α 2 2.1％
CDR3β 87 90.6％
4268-TCR5对 2 2.1％
总配对的TCR 17 17.7％
实施例10
该实施例证实了通过在自体T细胞内共培养被诱导以表达突变的p53的自体APC来鉴定患者4266中的抗-突变的p53 T细胞(“p53热点突变通用筛选”)。该实施例还证实了从患者4266分离四种抗-突变的p53TCR。
如图25-31针对患者4266所述进行实验。
将来自患者4266的TIL片段(F1-F24，n＝24)与用由无关、WT p53或经突变的p53序列组成的TMG电穿孔的自体APC共培养。在37℃下进行共培养过夜。使用ELISPOT测定评价IFN-γ的分泌。结果显示于图25中。对于淋巴细胞→活细胞(PI阴性)→CD3+(T细胞)设门后，通过流式细胞术评价4-1BB的表达。结果显示于图26中。
将来自患者4266的TIL片段(F1-F24，n＝24)与用肽媒介物(DMSO)或由WT p53-R248序列或经突变的p53-R248W序列组成的经纯化的(>95％，通过HPLC)25-个氨基酸的肽脉冲的自体APC共培养。在37℃下进行共培养过夜。使用ELISPOT测定评价IFN-γ的分泌。结果显示于图27中。对于淋巴细胞→活细胞(PI阴性)→CD3+(T细胞)设门后，通过流式细胞术评价4-1BB的表达。结果显示于图28中。
将Cos7细胞(每孔2.5x104个)涂铺在平底96孔板的各孔上。第二天，将细胞与来自患者4266的单独HLA等位基因共转染。次日，将细胞用无肽、DMSO、WT p53-R248肽SSCMGGMNRR(SEQ ID NO:590)或经突变的p53-R248W肽SSCMGGMNWR(SEQ ID NO:591)在37℃下以1μg/mL脉冲2小时。将来自患者4266的TIL培养物(105)添加至各孔并在37℃下共培养过夜。对于淋巴细胞→活细胞(PI阴性)→CD3+(T细胞)→CD4-CD8+设门后，通过流式细胞术评价4-1BB的表达。结果显示于图29中。
将对从4266-TIL鉴定的p53-R248W具有假定特异性的表达模拟物(无TCR)、4266-TCR1、4266-TCR2、4266-TCR3或4266-TCR4的T细胞与用肽媒介物(DMSO)或由WT p53-R248序列或经突变的p53-R248W序列组成的经纯化的(>95％，通过HPLC)25个氨基酸的肽脉冲的自体APC共培养。单独的培养基及PMA和离子霉素分别为阴性对照和阳性对照。在37℃下进行共培养过夜。对于淋巴细胞→活细胞(PI阴性)→CD3+(T细胞)→CD4-CD8+设门后，通过流式细胞术评价4-1BB的表达。结果显示于图30中。
肿瘤细胞(TC)系由从患者4266切除的异种移植的肿瘤碎片建立，然后通过免疫受损的小鼠连续传代(TC#4266)。将TC#4266与表达模拟物(无TCR)或p53-R248W-特异性TCR(4266-TCR2、4266-TCR3或4266-TCR4)的T细胞(105)在37℃下共培养过夜。将TC#4266细胞不与任何东西孵育、或者将TC#4266细胞与W6/32泛-HLA I类特异性阻断抗体、IVA12泛-HLAII类特异性阻断抗体或突变的p53-R248W肽SSCMGGMNWR(SEQ ID NO:591)在37℃下孵育2小时。将抗体以5μg/mL的终浓度保存在共培养物中。将肽以1μg/mL孵育，并且孵育后洗涤过量肽。单独的培养基(无TC)及PMA和离子霉素分别为阴性对照和阳性对照。对于淋巴细胞→活细胞(PI阴性)→CD3+(T细胞)→CD4-CD8+设门后，通过流式细胞术评价4-1BB的表达。结果示于图31中。
从患者4266分离的4266-TCR1的序列示于下文。从氨基末端开始，第一加下划线区是CDR1α(SEQ ID NO:97)，第二加下划线区是CDR2α(SEQ ID NO:98)，第三加下划线区是CDR3α(SEQ ID NO:99)，第四加下划线区是CDR1β(SEQ ID NO:100)，第五加下划线区是CDR2β(SEQ ID NO:101)，和第六加下划线区是CDR3β(SEQ ID NO:102)。粗体区是连接子(SEQ IDNO:26)。从氨基末端开始，第一加斜体区是α链恒定区(SEQ ID NO:23)并且第二加斜体区是β链恒定区(SEQ ID NO:25)。α链可变区(SEQ ID NO:103)包含从氨基末端开始并且在α链恒定区开始之前就结束的序列。β链可变区(SEQ ID NO:104)包含在连接子之后立即开始并且就在β链恒定区开始之前结束的序列。全长α链(SEQ ID NO:105)包含从氨基末端开始并且就在连接子开始之前结束的序列。全长β链(SEQ ID NO:106)包含在连接子之后立即开始并且以羧基末端结束的序列。
癌症反应性T细胞使用下面列出的筛选方法进行鉴定。用于分离TCR的方法示于下文。
TCR名称：4266-TCR1
P53突变的识别：R248W
筛选方法：p53“热点”突变通用筛选
共培养以鉴定TCR：共培养4266-F1、4266-F3、4266-F5和4266-F6与p53mutTMG或R248W长肽(两次共培养均检测相同的TCR)，分选CD8+41BB+T细胞
鉴定TCR的方法：单细胞RT-PCR
所有配对的TCR中的TCR的丰度：17.0％(在53对中观察到9次)
TCR取向：α-β
表达载体：SB转座子
MALLLVPAFQVIFTLGGTRAQSVTQLDSQVPVFEEAPVELRCNYSSSVSVYLFWYVQYPNQGLQLLLKYLSGSTLVESINGFEAEFNKSQTSFHLRKPSVHISDTAEYFCAVSDLVRDDKIIFGKGTRLHILPNIQNPEPAVYQLKDPRSQDSTLCLFTDFDSQINVPKTMESGTFITDKCVLDMKAMDSKSNGAIAWSNQTSFTCQDIFKETNATYPSSDVPCDATLTEKSFETDMNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSSRAKRSGSGATNFSLLKQAGDVEENPGPMHIGLLCCVAFSLLWASPVNAGVTQTPKFQVLKTGQSMTLQCAQDMNHNSMYWYRQDPGMGLRLIYYSASEGTTDKGEVPNGYNVSRLNKREFSLRLESAAPSQTSVYFCASIGGFEAFFGQGTRLTVVEDLRNVTPPKVSLFEPSKAEIANKQKATLVCLARGFFPDHVELSWWVNGKEVHSGVCTDPQAYKESNYSYCLSSRLRVSATFWHNPRNHFRCQVQFHGLSEEDKWPEGSPKPVTQNISAEAWGRADCGITSASYQQGVLSATILYEILLGKATLYAVLVSTLVVMAMVKRKNS(SEQ ID NO:583)
患者4266的TCR 4266-TCR1的统计数据示于下表30中。
表30
参数 # 频率
总孔 96 100％
CDR3α 9 9.4％
CDR3β 10 10.4％
4266-TCR1对 9 9.4％
总配对的TCR 53 55.2％
从患者4266分离的4266-TCR2的序列示于下文。从氨基末端开始，第一加下划线区是CDR1α(SEQ ID NO:107)，第二加下划线区是CDR2α(SEQ ID NO:108)，第三加下划线区是CDR3α(SEQ ID NO:109)，第四加下划线区是CDR1β(SEQ ID NO:110)，第五加下划线区是CDR2β(SEQ ID NO:111)，和第六加下划线区是CDR3β(SEQ ID NO:112)。粗体区是连接子(SEQ ID NO:26)。从氨基末端开始，第一加斜体区是α链恒定区(SEQ ID NO:23)并且第二加斜体区是β链恒定区(SEQ ID NO:25)。α链可变区(SEQ ID NO:113)包含从氨基末端开始并且在α链恒定区开始之前就结束的序列。β链可变区(SEQ ID NO:114)包含在连接子之后立即开始并且在β链恒定区开始之前就结束的序列。全长α链(SEQ ID NO:115)包含从氨基末端开始并且在连接子开始之前就结束的序列。全长β链(SEQ ID NO:116)包含在连接子之后立即开始并且以羧基末端结束的序列。
癌症反应性T细胞使用下面列出的筛选方法进行鉴定。用于分离TCR的方法示于下文。
TCR名称：4266-TCR2
P53突变的识别：R248W
筛选方法：p53“热点”突变通用筛选
共培养以鉴定TCR:共培养4266-F1、4266-F3、4266-F5和4266-F6与p53mutTMG或R248W长肽(两次共培养均检测相同的TCR)，分选CD8+41BB+T细胞
鉴定TCR的方法：单细胞RT-PCR
所有配对的TCR中的TCR的丰度：24.5％(在53对中观察到13次)
TCR取向：α-β
表达载体：SB转座子
MAGVFLLYVSMKMGGTTGQNIDQPTEMTATEGAIVQINCTYQTSGFNGLFWYQQHAGEAPTFLSYNVL DGLEEKGRFSSFLSRSKGYSYLLLKELQMKDSASYLCAVYTGGFKTIFGAGTRLFVKANIQNPEPAVYQLKDPRSQDSTLCLFTDFDSQINVPKTMESGTFITDKCVLDMKAMDSKSNGAIAWSNQTSFTCQDIFKETNATYPSSDVPCDATLTEKSFETDMNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSSRAKRSGSGATNFSLLKQAGDVEENPGPMHTRLLCWAALCLLGAELTEAGVAQSPRYKIIEKRQSVAFWCNPISGHATLYWYQQILGQGPKLLIQFQNNGVVDDSQLPKDRFSAERLKGVDSTLKIQPAKLEDSAVYLCASNLGGGSTDTQYFGPGTRLTVLEDLRNVTPPKVSLFEPSKAEIANKQKATLVCLARGFFPDHVELSWWVNGKEVHSGVCTDPQAYKESNYSYCLSSRLRVSATFWHNPRNHFRCQVQFHGLSEEDKWPEGSPKPVTQNISAEAWGRADCGITSASYQQGVLSATILYEILLGKATLYAVLVSTLVVMAMVKRKNS(SEQID NO:584)
患者4266的TCR 4266-TCR2的统计数据示于下表31中。
表31
参数 # 频率
总孔 96 100％
CDR3α 21 21.9％
CDR3β 18 18.8％
4266-TCR2对 13 13.5％
总配对的TCR 53 55.2％
从患者4266分离的4266-TCR3的序列示于下文。从氨基末端开始，第一加下划线区是CDR1α(SEQ ID NO:117)，第二加下划线区是CDR2α(SEQ ID NO:118)，第三加下划线区是CDR3α(SEQ ID NO:119)，第四加下划线区是CDR1β(SEQ ID NO:120)，第五加下划线区是CDR2β(SEQ ID NO:121)，和第六加下划线区是CDR3β(SEQ ID NO:122)。粗体区是连接子(SEQ ID NO:26)。从氨基末端开始，第一加斜体区是α链恒定区(SEQ ID NO:23)并且第二加斜体区是β链恒定区(SEQ ID NO:25)。α链可变区(SEQ ID NO:123)包含从氨基末端开始并且在α链恒定区开始之前就结束的序列。β链可变区(SEQ ID NO:124)包含在连接子之后立即开始并且在β链恒定区开始之前就结束的序列。全长α链(SEQ ID NO:125)包含从氨基末端开始并且就在连接子开始之前结束的序列。全长β链(SEQ ID NO:126)包含在连接子之后立即开始并且以羧基末端结束的序列。
癌症反应性T细胞使用下面列出的筛选方法进行鉴定。用于分离TCR的方法示于下文。
TCR名称：4266-TCR3
P53突变的识别：R248W
筛选方法：p53“热点”突变通用筛选
共培养以鉴定TCR：共培养4266-F1、4266-F3、4266-F5和4266-F6与p53mutTMG或R248W长肽(两次共培养均检测相同的TCR)，分选CD8+41BB+T细胞
鉴定TCR的方法：单细胞RT-PCR
所有配对的TCR中的TCR的丰度：34.0％(在53对中观察到18次)
TCR取向：α-β
表达载体：SB转座子
MAGVFLLYVSMKMGGTTGQNIDQPTEMTATEGAIVQINCTYQTSGFNGLFWYQQHAGEAPTFLSYNVL DGLEEKGRFSSFLSRSKGYSYLLLKELQMKDSASYLCAFYYGGSQGNLIFGKGTKLSVKPNIQNPEPAVYQLKDPRSQDSTLCLFTDFDSQINVPKTMESGTFITDKCVLDMKAMDSKSNGAIAWSNQTSFTCQDIFKETNATYPSSDVPCDATLTEKSFETDMNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSSRAKRSGSGATNFSLLKQAGDVEENPGPMHTRLLCWVVLGFLGTDHTGAGVSQSPRYKVAKRGQDVALRCDPISGHVSLFWYQQALGQGPEFLTYFQNEAQLDKSGLPSDRFFAERPEGSVSTLKIQRTQQEDSAVYLCASSFGSGSTDTQYFGPGTRLTVLEDLRNVTPPKVSLFEPSKAEIANKQKATLVCLARGFFPDHVELSWWVNGKEVHSGVCTDPQAYKESNYSYCLSSRLRVSATFWHNPRNHFRCQVQFHGLSEEDKWPEGSPKPVTQNISAEAWGRADCGITSASYQQGVLSATILYEILLGKATLYAVLVSTLVVMAMVKRKNS(SEQ ID NO:585)
患者4266的TCR 4266-TCR3的统计数据示于下表32中。
表32
参数 # 频率
总孔 96 100％
CDR3α 19 19.8％
CDR3β 26 27.1
4266-TCR3对 18 18.8％
总配对的TCR 53 55.2％
从患者4266分离的4266-TCR4的序列示于下文。从氨基末端开始，第一加下划线区是CDR1α(SEQ ID NO:127)，第二加下划线区是CDR2α(SEQ ID NO:128)，第三加下划线区是CDR3α(SEQ ID NO:129)，第四加下划线区是CDR1β(SEQ ID NO:130)，第五加下划线区是CDR2β(SEQ ID NO:131)，和第六加下划线区是CDR3β(SEQ ID NO:132)。粗体区是连接子(SEQ ID NO:26)。从氨基末端开始，第一加斜体区是α链恒定区(SEQ ID NO:23)并且第二加斜体区是β链恒定区(SEQ ID NO:25)。α链可变区(SEQ ID NO:133)包含从氨基末端开始并且就在α链恒定区开始之前结束的序列。β链可变区(SEQ ID NO:134)包含在连接子之后立即开始并且就在β链恒定区开始之前结束的序列。全长α链(SEQ ID NO:135)包含从氨基末端开始并且就在连接子开始之前结束的序列。全长β链(SEQ ID NO:136)包含在连接子之后立即开始并且以羧基末端结束的序列。
癌症反应性T细胞使用下面列出的筛选方法进行鉴定。用于分离TCR的方法示于下文。
TCR名称：4266-TCR4
P53突变的识别：R248W
筛选方法：p53“热点”突变通用筛选
共培养以鉴定TCR：共培养4266-F1、4266-F3、4266-F5和4266-F6与p53mutTMG或R248W长肽(两次共培养均检测相同的TCR)，分选CD8+41BB+T细胞
鉴定TCR的方法：单细胞RT-PCR
所有配对的TCR中的TCR的丰度：9.4％(在53对中观察到5次)
TCR取向：α-β
表达载体：SB转座子
MAGVFLLYVSMKMGGTTGQNIDQPTEMTATEGAIVQINCTYQTSGFNGLFWYQQHAGEAPTFLSYNVL DGLEEKGRFSSFLSRSKGYSYLLLKELQMKDSASYLCAVYPGGSQGNLIFGKGTKLSVKPNIQNPEPAVYQLKDPRSQDSTLCLFTDFDSQINVPKTMESGTFITDKCVLDMKAMDSKSNGAIAWSNQTSFTCQDIFKETNATYPSSDVPCDATLTEKSFETDMNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSSRAKRSGSGATNFSLLKQAGDVEENPGPMHTRLLCWAALCLLGAELTEAGVAQSPRYKIIEKRQSVAFWCNPISGHATLYWYQQILGQGPKLLIQFQNNGVVDDSQLPKDRFSAERLKGVDSTLKIQPAKLEDSAVYLCASSLGTGSTDTQYFGPGTRLTVLEDLRNVTPPKVSLFEPSKAEIANKQKATLVCLARGFFPDHVELSWWVNGKEVHSGVCTDPQAYKESNYSYCLSSRLRVSATFWHNPRNHFRCQVQFHGLSEEDKWPEGSPKPVTQNISAEAWGRADCGITSASYQQGVLSATILYEILLGKATLYAVLVSTLVVMAMVKRKNS(SEQ ID NO:586)
患者4266的TCR 4266-TCR4的统计数据示于下表33中。
表33
参数 # 频率
总孔 96 100％
CDR3α 5 5.2％
CDR3β 13 13.5
4266-TCR3对 5 5.2％
总配对的TCR 53 55.2％
实施例11
该实施例证实了通过在自体T细胞内共培养被诱导以表达突变的p53的自体APC来鉴定患者4252中的抗-突变的p53 T细胞(“p53热点突变通用筛选”)。
TIL片段F1、F3、F7和F19患者4252用作效应器。将T细胞效应器和自体APC(不成熟的DC)的共培养物(1)用由无关、WT p53或经突变的p53序列组成的TMG电穿孔或(2)用肽媒介物(DMSO)或由WT p53-R175序列或突变的p53-R175H序列组成的经纯化的(>95％，通过HPLC)25个氨基酸的肽脉冲。仅T细胞(无靶标)是阴性对照并且PMA和Iono是阳性对照。在37℃下进行共培养过夜。通过流式细胞术评价4-1BB在CD3+CD8-CD4+T细胞上的表达。结果显示于图38中。
实施例12
该实施例证实了通过在自体T细胞内共培养被诱导以表达突变的p53的自体APC来鉴定患者4270中的抗-突变的p53 T细胞(“p53热点突变通用筛选”)。
TIL片段F13和F16患者4270用作效应器。与T细胞效应器和自体APC(不成熟的DC)的共培养物(1)用由无关、WT p53或突变的p53序列组成的TMG电穿孔，或(2)用肽媒介物(DMSO)或由WT p53-R282序列或经突变的p53-R282W序列组成的经纯化的(>95％，通过HPLC)25个氨基酸的肽脉冲。T细胞仅是阴性对照，并且PMA和Iono是阳性对照。在37℃下进行共培养过夜。使用ELISPOT测定评价IFN-γ的分泌。结果显示于图39中。
实施例13
该实施例证实了通过在自体T细胞内共培养被诱导以表达突变的p53的自体APC来鉴定患者4285中的抗-突变的p53 T细胞(“p53热点突变通用筛选”)。
将来自患者4285的TIL片段(F1-F22和F24，n＝18)与用由无关、WT p53或经突变的p53序列组成的TMG电穿孔的自体APC共培养。在37℃下进行共培养过夜。使用ELISPOT测定评价IFN-γ的分泌。结果显示于图40中。对于淋巴细胞→活细胞(PI阴性)→CD3+(T细胞)设门后，通过流式细胞术评价4-1BB的表达。结果显示于图42中。
将来自患者4285的TIL片段(F1-F22和F24，n＝18)与用肽媒介物(DMSO)或由WTp53-R175序列或突变的p53-R175H序列组成的经纯化的(>95％，通过HPLC)25个氨基酸的肽脉冲的自体APC共培养。在37℃下进行共培养过夜。使用ELISPOT测定评价IFN-γ的分泌。结果显示于图41中。对于淋巴细胞→活细胞(PI阴性)→CD3+(T细胞)设门后，通过流式细胞术评价4-1BB的表达。结果显示于图43中。
将自体APC用来自p53-R175H序列(表34中加下划线的氨基酸取代)的重叠14个氨基酸的15个氨基酸的肽脉冲。将对p53-R175H具有特异性的来自患者4285的TIL(片段培养物10、6和9)与肽-脉冲的APC在37℃下共培养过夜。DMSO是肽媒介物。使用ELISPOT测定评价IFN-γ的分泌。结果显示于表34中。
表34
Figure BDA0002430898550000891
将Cos7细胞(每孔2.5x104个)涂铺在平底96孔板的孔上。第二天，将细胞与来自患者4285的单独HLA等位基因共转染。次日，将细胞用DMSO或经突变的p53-R175H肽YKQSQHMTEVVRHCPHHERCSDSDG(SEQ ID NO:2)在37℃下在10μg/mL下脉冲2小时。将来自患者4285的对p53-R175H具有特异性的选定TIL片段培养物(4285-F6、4285-F9和4285-F10)与经转染的Cos7细胞在37℃下共培养过夜。对于淋巴细胞→活→CD3+(T细胞)→CD8-CD4+设门后，通过流式细胞术测定4-1BB的表达。结果显示于图54中。
将自体APC用对应于WT或突变的p53-R175H序列的降低浓度的25-个或15-个氨基酸的肽在37℃下脉冲2小时。将来自患者4285的4285-TCR1转座的T细胞与肽-脉冲的APC在37℃下共培养过夜。对于淋巴细胞→活→CD3+(T细胞)→CD8-CD4+设门后，通过流式细胞术测定4-1BB的表达。结果显示于图55中。
从患者4285分离的4285-TCR1的序列示于下文。从氨基末端开始，第一加下划线区是CDR1α(SEQ ID NO:487)，第二加下划线区是CDR2α(SEQ ID NO:488)，第三加下划线区是CDR3α(SEQ ID NO:489)，第四加下划线区是CDR1β(SEQ ID NO:490)，第五加下划线区是CDR2β(SEQ ID NO:491)，和第六加下划线区是CDR3β(SEQ ID NO:492)。粗体区是连接子(SEQ ID NO:26)。从氨基末端开始，第一加斜体区是α链恒定区(SEQ ID NO:23)并且第二加斜体区是β链恒定区(SEQ ID NO:25)。α链可变区(SEQ ID NO:493)包含从氨基末端开始并且就在α链恒定区开始之前结束的序列。β链可变区(SEQ ID NO:494)包含在连接子之后立即开始并且就在β链恒定区开始之前结束的序列。全长α链(SEQ ID NO:495)包含从氨基末端开始并且就在连接子开始之前结束的序列。全长β链(SEQ ID NO:496)包含在连接子之后立即开始并且以羧基末端结束的序列。
癌症反应性T细胞如下所述鉴定。TCR如下所述分离。
TCR名称：4285-TCR1
P53突变的识别：R175H
筛选方法：p53“热点”突变通用筛选
共培养以鉴定TCR：共培养4285-F6与p53-R175H肽和分选CD4+41BB+T细胞
鉴定TCR的方法：单细胞RT-PCR
所有配对的TCR中的TCR的丰度：81.8％(在44对中观察到36次)
TCR取向：α-β
表达载体：SB转座子
MAKNPLAAPLLILWFHLDCVSSILNVEQSPQSLHVQEGDSTNFTCSFPSSNFYALHWYRWETAKSPEALFVMTLNGDEKKKGRISATLNTKEGYSYLYIKGSQPEDSATYLCALITGGGNKLTFGTGTQLKVELNIQNPEPAVYQLKDPRSQDSTLCLFTDFDSQINVPKTMESGTFITDKCVLDMKAMDSKSNGAIAWSNQTSFTCQDIFKETNATYPSSDVPCDATLTEKSFETDMNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSSRAKRSGSGATNFSLLKQAGDVEENPGPMHLGLLCCGAFSLLWAGPVNAGVTQTPKFRVLKTGQSMTLLCAQDMNHEYMYWYRQDPGMGLRLIHYSVGEGTTAKGEVPDGYNVSRLKKQNFLLGLESAAPSQTSVYFCASRLQGWNSPLHFGNGTRLTVTEDLRNVTPPKVSLFEPSKAEIANKQKATLVCLARGFFPDHVELSWWVNGKEVHSGVCTDPQAYKESNYSYCLSSRLRVSATFWHNPRNHFRCQVQFHGLSEEDKWPEGSPKPVTQNISAEAWGRADCGITSASYQQGVLSATILYEILLGKATLYAVLVSTLVVMAMVKRKNS(SEQ ID NO:589)
患者4285的4285-TCR1的统计数据示于下表35中。
表35
参数 # 频率
总孔 96 100％
CDR3α 37 39.8％
CDR3β 39 40.6％
4285-TCR1对 36 37.5％
总配对的TCR 44 45.8％
实施例14
该实施例证实了T细胞对p53“热点”突变的响应的概述。
表36提供了T细胞对p53“热点”突变的响应的概述。表36的第1-15号是一项回顾性研究。表36的第16-33号是一项前瞻性研究。
表36
Figure BDA0002430898550000911
Figure BDA0002430898550000921
n/a＝不适用；N＝阴性；Y＝确认有反应性；TBS＝待筛选。
实施例15
该实施例证实了用p53突变-反应性TIL治疗患者。
表37提供了用p53突变-反应性TIL治疗患者的概述。
表37
Figure BDA0002430898550000931
NT＝未治疗；TBS＝待筛选；N.R.＝无响应；P.R.＝部分响应；**患者尚未治疗。
实施例16
该实施例证实了在所有测序的肿瘤中每种错义p53突变的总频率。
如下采集样品：从141名癌症患者中收集了肿瘤和PBL。TIL从肿瘤生长。对肿瘤样品进行外显子组和转录组测序。鉴定了Tp53突变。在150个肿瘤中，30％表达WT p53，而70％表达经突变的p53。在表达突变的p53的122个肿瘤样品中，73％表达错义突变，13％表达终止-获得突变，11％表达移码突变，并且3％表达插入缺失突变。
图44显示了所有测序肿瘤中每种错义p53突变的总频率。
实施例17
该实施例证实了实施例1-15的TCR的反应性的概述。
将表38的TCR分离，在T细胞中表达并针对相关抗原进行了测试。结果概述显示于表38中。
表38
Figure BDA0002430898550000941
Figure BDA0002430898550000951
本文引用的所有参考文献，包括出版物、专利申请和专利，均通过引用并入本文，其程度如同每篇参考文献均被单独且具体地指示为通过引用并入本文并在本文中整体阐述。
在描述本发明的上下文中(尤其是在所附权利要求的上下文中)术语“一个”和“一种”和“该”和“至少一种”以及类似指代物的使用应被解释为涵盖了单数和复数两种，除非本文另有说明或与上下文明显矛盾。术语“至少一种”之后是一项或多项的列表(例如，“A和B中的至少一种”)的使用应理解为意指选自所列项(A或B)的一项或所列项(A和B)的两种或多种的任何组合，除非本文另有说明或与上下文明显矛盾。除非另有说明，否则术语“包含”、“具有”、“包括”和“含有”应被解释为开放式术语(即，意指“包括但不限于”)。除非在本文中另外指出，否则本文中数值范围的叙述仅旨在用作分别指代落入该范围内的每个单独值的简写方法，并且每个单独值都被并入说明书中，就好像它在本文中被单独叙述一样。除非本文另外指出或另外与上下文明显矛盾，否则本文描述的所有方法可以以任何适合的顺序执行。除非另外要求保护，否则本文提供的任何和所有示例或示例性语言(如，“诸如”)的使用仅旨在更好地阐明本发明，并且不对本发明的范围构成限制。说明书中的任何语言都不应解释为指示任何未要求保护的要素对于实施本发明必不可少。
本文描述了本发明的优选实施方案，包括发明人已知的用于实施本发明的最佳模式。在阅读前述说明书之后，那些优选实施方案的变型对于本领域普通技术人员而言将变得显而易见。本发明人期望熟练的技术人员适当地采用这样的变型，并且本发明人希望以不同于本文具体描述的方式来实践本发明。因此，本发明包括适用法律所允许的所附权利要求书中记载的主题的所有修改和等同物。此外，除非本文另外指出或另外与上下文明显矛盾，否则本发明涵盖上述要素在其所有可能的变型中的任何组合。
序列表
<110> THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE
SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES
<120> 分离对P53癌症-特异性突变具有抗原特异性的T细胞的方法
<130> 740175
<150> US 62/565,464
<151> 2017-09-29
<160> 602
<170> PatentIn 3.5版
<210> 1
<211> 393
<212> PRT
<213> 智人(Homo sapiens)
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1 5 10 15
His Glu Arg Cys Ser Asp Ser Asp Gly
20 25
<210> 3
<211> 25
<212> PRT
<213> 智人(Homo sapiens)
<400> 3
Ser Gly Asn Leu Leu Gly Arg Asn Ser Phe Glu Val His Val Cys Ala
1 5 10 15
Cys Pro Gly Arg Asp Arg Arg Thr Glu
20 25
<210> 4
<211> 25
<212> PRT
<213> 智人(Homo sapiens)
<400> 4
Tyr Met Cys Asn Ser Ser Cys Met Gly Gly Met Asn Leu Arg Pro Ile
1 5 10 15
Leu Thr Ile Ile Thr Leu Glu Asp Ser
20 25
<210> 5
<211> 25
<212> PRT
<213> 智人(Homo sapiens)
<400> 5
Phe Glu Val Arg Val Cys Ala Cys Pro Gly Arg Asp Trp Arg Thr Glu
1 5 10 15
Glu Glu Asn Leu Arg Lys Lys Gly Glu
20 25
<210> 6
<211> 25
<212> PRT
<213> 智人(Homo sapiens)
<400> 6
Ser Gly Asn Leu Leu Gly Arg Asn Ser Phe Glu Val Cys Val Cys Ala
1 5 10 15
Cys Pro Gly Arg Asp Arg Arg Thr Glu
20 25
<210> 7
<211> 25
<212> PRT
<213> 智人(Homo sapiens)
<400> 7
His Tyr Asn Tyr Met Cys Asn Ser Ser Cys Met Gly Ser Met Asn Arg
1 5 10 15
Arg Pro Ile Leu Thr Ile Ile Thr Leu
20 25
<210> 8
<211> 25
<212> PRT
<213> 智人(Homo sapiens)
<400> 8
Tyr Met Cys Asn Ser Ser Cys Met Gly Gly Met Asn Gln Arg Pro Ile
1 5 10 15
Leu Thr Ile Ile Thr Leu Glu Asp Ser
20 25
<210> 9
<211> 25
<212> PRT
<213> 智人(Homo sapiens)
<400> 9
His Tyr Asn Tyr Met Cys Asn Ser Ser Cys Met Gly Asp Met Asn Arg
1 5 10 15
Arg Pro Ile Leu Thr Ile Ile Thr Leu
20 25
<210> 10
<211> 25
<212> PRT
<213> 智人(Homo sapiens)
<400> 10
Ser Gly Asn Leu Leu Gly Arg Asn Ser Phe Glu Val Leu Val Cys Ala
1 5 10 15
Cys Pro Gly Arg Asp Arg Arg Thr Glu
20 25
<210> 11
<211> 25
<212> PRT
<213> 智人(Homo sapiens)
<400> 11
Tyr Met Cys Asn Ser Ser Cys Met Gly Gly Met Asn Trp Arg Pro Ile
1 5 10 15
Leu Thr Ile Ile Thr Leu Glu Asp Ser
20 25
<210> 12
<211> 25
<212> PRT
<213> 智人(Homo sapiens)
<400> 12
Asp Arg Asn Thr Phe Arg His Ser Val Val Val Pro Cys Glu Pro Pro
1 5 10 15
Glu Val Gly Ser Asp Cys Thr Thr Ile
20 25
<210> 13
<211> 25
<212> PRT
<213> 智人(Homo sapiens)
<400> 13
Met Cys Asn Ser Ser Cys Met Gly Gly Met Asn Arg Ser Pro Ile Leu
1 5 10 15
Thr Ile Ile Thr Leu Glu Asp Ser Ser
20 25
<210> 14
<211> 300
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 14
Tyr Lys Gln Ser Gln His Met Thr Glu Val Val Arg His Cys Pro His
1 5 10 15
His Glu Arg Cys Ser Asp Ser Asp Gly Ser Gly Asn Leu Leu Gly Arg
20 25 30
Asn Ser Phe Glu Val His Val Cys Ala Cys Pro Gly Arg Asp Arg Arg
35 40 45
Thr Glu Tyr Met Cys Asn Ser Ser Cys Met Gly Gly Met Asn Leu Arg
50 55 60
Pro Ile Leu Thr Ile Ile Thr Leu Glu Asp Ser Phe Glu Val Arg Val
65 70 75 80
Cys Ala Cys Pro Gly Arg Asp Trp Arg Thr Glu Glu Glu Asn Leu Arg
85 90 95
Lys Lys Gly Glu Ser Gly Asn Leu Leu Gly Arg Asn Ser Phe Glu Val
100 105 110
Cys Val Cys Ala Cys Pro Gly Arg Asp Arg Arg Thr Glu His Tyr Asn
115 120 125
Tyr Met Cys Asn Ser Ser Cys Met Gly Ser Met Asn Arg Arg Pro Ile
130 135 140
Leu Thr Ile Ile Thr Leu Tyr Met Cys Asn Ser Ser Cys Met Gly Gly
145 150 155 160
Met Asn Gln Arg Pro Ile Leu Thr Ile Ile Thr Leu Glu Asp Ser His
165 170 175
Tyr Asn Tyr Met Cys Asn Ser Ser Cys Met Gly Asp Met Asn Arg Arg
180 185 190
Pro Ile Leu Thr Ile Ile Thr Leu Ser Gly Asn Leu Leu Gly Arg Asn
195 200 205
Ser Phe Glu Val Leu Val Cys Ala Cys Pro Gly Arg Asp Arg Arg Thr
210 215 220
Glu Tyr Met Cys Asn Ser Ser Cys Met Gly Gly Met Asn Trp Arg Pro
225 230 235 240
Ile Leu Thr Ile Ile Thr Leu Glu Asp Ser Asp Arg Asn Thr Phe Arg
245 250 255
His Ser Val Val Val Pro Cys Glu Pro Pro Glu Val Gly Ser Asp Cys
260 265 270
Thr Thr Ile Met Cys Asn Ser Ser Cys Met Gly Gly Met Asn Arg Ser
275 280 285
Pro Ile Leu Thr Ile Ile Thr Leu Glu Asp Ser Ser
290 295 300
<210> 15
<211> 25
<212> PRT
<213> 智人(Homo sapiens)
<400> 15
Tyr Lys Gln Ser Gln His Met Thr Glu Val Val Arg Arg Cys Pro His
1 5 10 15
His Glu Arg Cys Ser Asp Ser Asp Gly
20 25
<210> 16
<211> 25
<212> PRT
<213> 智人(Homo sapiens)
<400> 16
Ser Gly Asn Leu Leu Gly Arg Asn Ser Phe Glu Val Arg Val Cys Ala
1 5 10 15
Cys Pro Gly Arg Asp Arg Arg Thr Glu
20 25
<210> 17
<211> 25
<212> PRT
<213> 智人(Homo sapiens)
<400> 17
Tyr Met Cys Asn Ser Ser Cys Met Gly Gly Met Asn Arg Arg Pro Ile
1 5 10 15
Leu Thr Ile Ile Thr Leu Glu Asp Ser
20 25
<210> 18
<211> 25
<212> PRT
<213> 智人(Homo sapiens)
<400> 18
Phe Glu Val Arg Val Cys Ala Cys Pro Gly Arg Asp Arg Arg Thr Glu
1 5 10 15
Glu Glu Asn Leu Arg Lys Lys Gly Glu
20 25
<210> 19
<211> 25
<212> PRT
<213> 智人(Homo sapiens)
<400> 19
His Tyr Asn Tyr Met Cys Asn Ser Ser Cys Met Gly Gly Met Asn Arg
1 5 10 15
Arg Pro Ile Leu Thr Ile Ile Thr Leu
20 25
<210> 20
<211> 25
<212> PRT
<213> 智人(Homo sapiens)
<400> 20
Asp Arg Asn Thr Phe Arg His Ser Val Val Val Pro Tyr Glu Pro Pro
1 5 10 15
Glu Val Gly Ser Asp Cys Thr Thr Ile
20 25
<210> 21
<211> 25
<212> PRT
<213> 智人(Homo sapiens)
<400> 21
Met Cys Asn Ser Ser Cys Met Gly Gly Met Asn Arg Arg Pro Ile Leu
1 5 10 15
Thr Ile Ile Thr Leu Glu Asp Ser Ser
20 25
<210> 22
<211> 300
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 22
Tyr Lys Gln Ser Gln His Met Thr Glu Val Val Arg Arg Cys Pro His
1 5 10 15
His Glu Arg Cys Ser Asp Ser Asp Gly Ser Gly Asn Leu Leu Gly Arg
20 25 30
Asn Ser Phe Glu Val Arg Val Cys Ala Cys Pro Gly Arg Asp Arg Arg
35 40 45
Thr Glu Tyr Met Cys Asn Ser Ser Cys Met Gly Gly Met Asn Arg Arg
50 55 60
Pro Ile Leu Thr Ile Ile Thr Leu Glu Asp Ser Phe Glu Val Arg Val
65 70 75 80
Cys Ala Cys Pro Gly Arg Asp Arg Arg Thr Glu Glu Glu Asn Leu Arg
85 90 95
Lys Lys Gly Glu Ser Gly Asn Leu Leu Gly Arg Asn Ser Phe Glu Val
100 105 110
Arg Val Cys Ala Cys Pro Gly Arg Asp Arg Arg Thr Glu His Tyr Asn
115 120 125
Tyr Met Cys Asn Ser Ser Cys Met Gly Gly Met Asn Arg Arg Pro Ile
130 135 140
Leu Thr Ile Ile Thr Leu Tyr Met Cys Asn Ser Ser Cys Met Gly Gly
145 150 155 160
Met Asn Arg Arg Pro Ile Leu Thr Ile Ile Thr Leu Glu Asp Ser His
165 170 175
Tyr Asn Tyr Met Cys Asn Ser Ser Cys Met Gly Gly Met Asn Arg Arg
180 185 190
Pro Ile Leu Thr Ile Ile Thr Leu Ser Gly Asn Leu Leu Gly Arg Asn
195 200 205
Ser Phe Glu Val Arg Val Cys Ala Cys Pro Gly Arg Asp Arg Arg Thr
210 215 220
Glu Tyr Met Cys Asn Ser Ser Cys Met Gly Gly Met Asn Arg Arg Pro
225 230 235 240
Ile Leu Thr Ile Ile Thr Leu Glu Asp Ser Asp Arg Asn Thr Phe Arg
245 250 255
His Ser Val Val Val Pro Tyr Glu Pro Pro Glu Val Gly Ser Asp Cys
260 265 270
Thr Thr Ile Met Cys Asn Ser Ser Cys Met Gly Gly Met Asn Arg Arg
275 280 285
Pro Ile Leu Thr Ile Ile Thr Leu Glu Asp Ser Ser
290 295 300
<210> 23
<211> 137
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 23
Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr Gln Leu Lys Asp Pro Arg
1 5 10 15
Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr Asp Phe Asp Ser Gln Ile
20 25 30
Asn Val Pro Lys Thr Met Glu Ser Gly Thr Phe Ile Thr Asp Lys Cys
35 40 45
Val Leu Asp Met Lys Ala Met Asp Ser Lys Ser Asn Gly Ala Ile Ala
50 55 60
Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln Asp Ile Phe Lys Glu Thr
65 70 75 80
Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro Cys Asp Ala Thr Leu Thr
85 90 95
Glu Lys Ser Phe Glu Thr Asp Met Asn Leu Asn Phe Gln Asn Leu Leu
100 105 110
Val Ile Val Leu Arg Ile Leu Leu Leu Lys Val Ala Gly Phe Asn Leu
115 120 125
Leu Met Thr Leu Arg Leu Trp Ser Ser
130 135
<210> 24
<211> 137
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 24
Asp Ile Gln Asn Pro Glu Pro Ala Val Tyr Gln Leu Lys Asp Pro Arg
1 5 10 15
Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr Asp Phe Asp Ser Gln Ile
20 25 30
Asn Val Pro Lys Thr Met Glu Ser Gly Thr Phe Ile Thr Asp Lys Cys
35 40 45
Val Leu Asp Met Lys Ala Met Asp Ser Lys Ser Asn Gly Ala Ile Ala
50 55 60
Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln Asp Ile Phe Lys Glu Thr
65 70 75 80
Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro Cys Asp Ala Thr Leu Thr
85 90 95
Glu Lys Ser Phe Glu Thr Asp Met Asn Leu Asn Phe Gln Asn Leu Leu
100 105 110
Val Ile Val Leu Arg Ile Leu Leu Leu Lys Val Ala Gly Phe Asn Leu
115 120 125
Leu Met Thr Leu Arg Leu Trp Ser Ser
130 135
<210> 25
<211> 173
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 25
Glu Asp Leu Arg Asn Val Thr Pro Pro Lys Val Ser Leu Phe Glu Pro
1 5 10 15
Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys Ala Thr Leu Val Cys Leu
20 25 30
Ala Arg Gly Phe Phe Pro Asp His Val Glu Leu Ser Trp Trp Val Asn
35 40 45
Gly Lys Glu Val His Ser Gly Val Cys Thr Asp Pro Gln Ala Tyr Lys
50 55 60
Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser Arg Leu Arg Val Ser Ala
65 70 75 80
Thr Phe Trp His Asn Pro Arg Asn His Phe Arg Cys Gln Val Gln Phe
85 90 95
His Gly Leu Ser Glu Glu Asp Lys Trp Pro Glu Gly Ser Pro Lys Pro
100 105 110
Val Thr Gln Asn Ile Ser Ala Glu Ala Trp Gly Arg Ala Asp Cys Gly
115 120 125
Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val Leu Ser Ala Thr Ile Leu
130 135 140
Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu Tyr Ala Val Leu Val Ser
145 150 155 160
Thr Leu Val Val Met Ala Met Val Lys Arg Lys Asn Ser
165 170
<210> 26
<211> 27
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 26
Arg Ala Lys Arg Ser Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys
1 5 10 15
Gln Ala Gly Asp Val Glu Glu Asn Pro Gly Pro
20 25
<210> 27
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 27
Tyr Gly Gly Thr Val Asn
1 5
<210> 28
<211> 8
<212> PRT
<213> 智人(Homo sapiens)
<400> 28
Tyr Phe Ser Gly Asp Pro Leu Val
1 5
<210> 29
<211> 11
<212> PRT
<213> 智人(Homo sapiens)
<400> 29
Cys Ala Val Lys Gly Asp Tyr Lys Leu Ser Phe
1 5 10
<210> 30
<211> 5
<212> PRT
<213> 智人(Homo sapiens)
<400> 30
Ser Gly His Ala Thr
1 5
<210> 31
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 31
Phe Gln Asn Asn Gly Val
1 5
<210> 32
<211> 12
<212> PRT
<213> 智人(Homo sapiens)
<400> 32
Cys Ala Ser Ser Leu Val Asn Thr Glu Ala Phe Phe
1 5 10
<210> 33
<211> 130
<212> PRT
<213> 智人(Homo sapiens)
<400> 33
Met Leu Leu Leu Leu Ile Pro Val Leu Gly Met Ile Phe Ala Leu Arg
1 5 10 15
Asp Ala Arg Ala Gln Ser Val Ser Gln His Asn His His Val Ile Leu
20 25 30
Ser Glu Ala Ala Ser Leu Glu Leu Gly Cys Asn Tyr Ser Tyr Gly Gly
35 40 45
Thr Val Asn Leu Phe Trp Tyr Val Gln Tyr Pro Gly Gln His Leu Gln
50 55 60
Leu Leu Leu Lys Tyr Phe Ser Gly Asp Pro Leu Val Lys Gly Ile Lys
65 70 75 80
Gly Phe Glu Ala Glu Phe Ile Lys Ser Lys Phe Ser Phe Asn Leu Arg
85 90 95
Lys Pro Ser Val Gln Trp Ser Asp Thr Ala Glu Tyr Phe Cys Ala Val
100 105 110
Lys Gly Asp Tyr Lys Leu Ser Phe Gly Ala Gly Thr Thr Val Thr Val
115 120 125
Arg Ala
130
<210> 34
<211> 131
<212> PRT
<213> 智人(Homo sapiens)
<400> 34
Met Ala Thr Arg Leu Leu Cys Trp Ala Ala Leu Cys Leu Leu Gly Ala
1 5 10 15
Glu Leu Thr Glu Ala Gly Val Ala Gln Ser Pro Arg Tyr Lys Ile Ile
20 25 30
Glu Lys Arg Gln Ser Val Ala Phe Trp Cys Asn Pro Ile Ser Gly His
35 40 45
Ala Thr Leu Tyr Trp Tyr Gln Gln Ile Leu Gly Gln Gly Pro Lys Leu
50 55 60
Leu Ile Gln Phe Gln Asn Asn Gly Val Val Asp Asp Ser Gln Leu Pro
65 70 75 80
Lys Asp Arg Phe Ser Ala Glu Arg Leu Lys Gly Val Asp Ser Thr Leu
85 90 95
Lys Ile Gln Pro Ala Lys Leu Glu Asp Ser Ala Val Tyr Leu Cys Ala
100 105 110
Ser Ser Leu Val Asn Thr Glu Ala Phe Phe Gly Gln Gly Thr Arg Leu
115 120 125
Thr Val Val
130
<210> 35
<211> 267
<212> PRT
<213> 智人(Homo sapiens)
<400> 35
Met Leu Leu Leu Leu Ile Pro Val Leu Gly Met Ile Phe Ala Leu Arg
1 5 10 15
Asp Ala Arg Ala Gln Ser Val Ser Gln His Asn His His Val Ile Leu
20 25 30
Ser Glu Ala Ala Ser Leu Glu Leu Gly Cys Asn Tyr Ser Tyr Gly Gly
35 40 45
Thr Val Asn Leu Phe Trp Tyr Val Gln Tyr Pro Gly Gln His Leu Gln
50 55 60
Leu Leu Leu Lys Tyr Phe Ser Gly Asp Pro Leu Val Lys Gly Ile Lys
65 70 75 80
Gly Phe Glu Ala Glu Phe Ile Lys Ser Lys Phe Ser Phe Asn Leu Arg
85 90 95
Lys Pro Ser Val Gln Trp Ser Asp Thr Ala Glu Tyr Phe Cys Ala Val
100 105 110
Lys Gly Asp Tyr Lys Leu Ser Phe Gly Ala Gly Thr Thr Val Thr Val
115 120 125
Arg Ala Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr Gln Leu Lys Asp
130 135 140
Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr Asp Phe Asp Ser
145 150 155 160
Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr Phe Ile Thr Asp
165 170 175
Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys Ser Asn Gly Ala
180 185 190
Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln Asp Ile Phe Lys
195 200 205
Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro Cys Asp Ala Thr
210 215 220
Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu Asn Phe Gln Asn
225 230 235 240
Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys Val Ala Gly Phe
245 250 255
Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser
260 265
<210> 36
<211> 304
<212> PRT
<213> 智人(Homo sapiens)
<400> 36
Met Ala Thr Arg Leu Leu Cys Trp Ala Ala Leu Cys Leu Leu Gly Ala
1 5 10 15
Glu Leu Thr Glu Ala Gly Val Ala Gln Ser Pro Arg Tyr Lys Ile Ile
20 25 30
Glu Lys Arg Gln Ser Val Ala Phe Trp Cys Asn Pro Ile Ser Gly His
35 40 45
Ala Thr Leu Tyr Trp Tyr Gln Gln Ile Leu Gly Gln Gly Pro Lys Leu
50 55 60
Leu Ile Gln Phe Gln Asn Asn Gly Val Val Asp Asp Ser Gln Leu Pro
65 70 75 80
Lys Asp Arg Phe Ser Ala Glu Arg Leu Lys Gly Val Asp Ser Thr Leu
85 90 95
Lys Ile Gln Pro Ala Lys Leu Glu Asp Ser Ala Val Tyr Leu Cys Ala
100 105 110
Ser Ser Leu Val Asn Thr Glu Ala Phe Phe Gly Gln Gly Thr Arg Leu
115 120 125
Thr Val Val Glu Asp Leu Arg Asn Val Thr Pro Pro Lys Val Ser Leu
130 135 140
Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys Ala Thr Leu
145 150 155 160
Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu Leu Ser Trp
165 170 175
Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr Asp Pro Gln
180 185 190
Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser Arg Leu Arg
195 200 205
Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe Arg Cys Gln
210 215 220
Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro Glu Gly Ser
225 230 235 240
Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp Gly Arg Ala
245 250 255
Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val Leu Ser Ala
260 265 270
Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu Tyr Ala Val
275 280 285
Leu Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg Lys Asn Ser
290 295 300
<210> 37
<211> 7
<212> PRT
<213> 智人(Homo sapiens)
<400> 37
Thr Arg Asp Thr Thr Tyr Tyr
1 5
<210> 38
<211> 8
<212> PRT
<213> 智人(Homo sapiens)
<400> 38
Arg Asn Ser Phe Asp Glu Gln Asn
1 5
<210> 39
<211> 14
<212> PRT
<213> 智人(Homo sapiens)
<400> 39
Cys Ala Leu Ser Glu Gly Gly Ser Asn Tyr Lys Leu Thr Phe
1 5 10
<210> 40
<211> 5
<212> PRT
<213> 智人(Homo sapiens)
<400> 40
Leu Asn His Asn Val
1 5
<210> 41
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 41
Tyr Tyr Asp Lys Asp Phe
1 5
<210> 42
<211> 14
<212> PRT
<213> 智人(Homo sapiens)
<400> 42
Cys Ala Thr Ser Arg Glu Leu Arg Gly Asn Glu Gln Phe Phe
1 5 10
<210> 43
<211> 135
<212> PRT
<213> 智人(Homo sapiens)
<400> 43
Met Leu Thr Ala Ser Leu Leu Arg Ala Val Ile Ala Ser Ile Cys Val
1 5 10 15
Val Ser Ser Met Ala Gln Lys Val Thr Gln Ala Gln Thr Glu Ile Ser
20 25 30
Val Val Glu Lys Glu Asp Val Thr Leu Asp Cys Val Tyr Glu Thr Arg
35 40 45
Asp Thr Thr Tyr Tyr Leu Phe Trp Tyr Lys Gln Pro Pro Ser Gly Glu
50 55 60
Leu Val Phe Leu Ile Arg Arg Asn Ser Phe Asp Glu Gln Asn Glu Ile
65 70 75 80
Ser Gly Arg Tyr Ser Trp Asn Phe Gln Lys Ser Thr Ser Ser Phe Asn
85 90 95
Phe Thr Ile Thr Ala Ser Gln Val Val Asp Ser Ala Val Tyr Phe Cys
100 105 110
Ala Leu Ser Glu Gly Gly Ser Asn Tyr Lys Leu Thr Phe Gly Lys Gly
115 120 125
Thr Leu Leu Thr Val Asn Pro
130 135
<210> 44
<211> 132
<212> PRT
<213> 智人(Homo sapiens)
<400> 44
Met Ala Pro Gly Leu Leu His Trp Met Ala Leu Cys Leu Leu Gly Thr
1 5 10 15
Gly His Gly Asp Ala Met Val Ile Gln Asn Pro Arg Tyr Gln Val Thr
20 25 30
Gln Phe Gly Lys Pro Val Thr Leu Ser Cys Ser Gln Thr Leu Asn His
35 40 45
Asn Val Met Tyr Trp Tyr Gln Gln Lys Ser Ser Gln Ala Pro Lys Leu
50 55 60
Leu Phe His Tyr Tyr Asp Lys Asp Phe Asn Asn Glu Ala Asp Thr Pro
65 70 75 80
Asp Asn Phe Gln Ser Arg Arg Pro Asn Thr Ser Phe Cys Phe Leu Asp
85 90 95
Ile Arg Ser Pro Gly Leu Gly Asp Ala Ala Met Tyr Leu Cys Ala Thr
100 105 110
Ser Arg Glu Leu Arg Gly Asn Glu Gln Phe Phe Gly Pro Gly Thr Arg
115 120 125
Leu Thr Val Leu
130
<210> 45
<211> 272
<212> PRT
<213> 智人(Homo sapiens)
<400> 45
Met Leu Thr Ala Ser Leu Leu Arg Ala Val Ile Ala Ser Ile Cys Val
1 5 10 15
Val Ser Ser Met Ala Gln Lys Val Thr Gln Ala Gln Thr Glu Ile Ser
20 25 30
Val Val Glu Lys Glu Asp Val Thr Leu Asp Cys Val Tyr Glu Thr Arg
35 40 45
Asp Thr Thr Tyr Tyr Leu Phe Trp Tyr Lys Gln Pro Pro Ser Gly Glu
50 55 60
Leu Val Phe Leu Ile Arg Arg Asn Ser Phe Asp Glu Gln Asn Glu Ile
65 70 75 80
Ser Gly Arg Tyr Ser Trp Asn Phe Gln Lys Ser Thr Ser Ser Phe Asn
85 90 95
Phe Thr Ile Thr Ala Ser Gln Val Val Asp Ser Ala Val Tyr Phe Cys
100 105 110
Ala Leu Ser Glu Gly Gly Ser Asn Tyr Lys Leu Thr Phe Gly Lys Gly
115 120 125
Thr Leu Leu Thr Val Asn Pro Asn Ile Gln Asn Pro Glu Pro Ala Val
130 135 140
Tyr Gln Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe
145 150 155 160
Thr Asp Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly
165 170 175
Thr Phe Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser
180 185 190
Lys Ser Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys
195 200 205
Gln Asp Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val
210 215 220
Pro Cys Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn
225 230 235 240
Leu Asn Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu
245 250 255
Lys Val Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser
260 265 270
<210> 46
<211> 305
<212> PRT
<213> 智人(Homo sapiens)
<400> 46
Met Ala Pro Gly Leu Leu His Trp Met Ala Leu Cys Leu Leu Gly Thr
1 5 10 15
Gly His Gly Asp Ala Met Val Ile Gln Asn Pro Arg Tyr Gln Val Thr
20 25 30
Gln Phe Gly Lys Pro Val Thr Leu Ser Cys Ser Gln Thr Leu Asn His
35 40 45
Asn Val Met Tyr Trp Tyr Gln Gln Lys Ser Ser Gln Ala Pro Lys Leu
50 55 60
Leu Phe His Tyr Tyr Asp Lys Asp Phe Asn Asn Glu Ala Asp Thr Pro
65 70 75 80
Asp Asn Phe Gln Ser Arg Arg Pro Asn Thr Ser Phe Cys Phe Leu Asp
85 90 95
Ile Arg Ser Pro Gly Leu Gly Asp Ala Ala Met Tyr Leu Cys Ala Thr
100 105 110
Ser Arg Glu Leu Arg Gly Asn Glu Gln Phe Phe Gly Pro Gly Thr Arg
115 120 125
Leu Thr Val Leu Glu Asp Leu Arg Asn Val Thr Pro Pro Lys Val Ser
130 135 140
Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys Ala Thr
145 150 155 160
Leu Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu Leu Ser
165 170 175
Trp Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr Asp Pro
180 185 190
Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser Arg Leu
195 200 205
Arg Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe Arg Cys
210 215 220
Gln Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro Glu Gly
225 230 235 240
Ser Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp Gly Arg
245 250 255
Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val Leu Ser
260 265 270
Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu Tyr Ala
275 280 285
Val Leu Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg Lys Asn
290 295 300
Ser
305
<210> 47
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 47
Thr Ser Gly Phe Asn Gly
1 5
<210> 48
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 48
Asn Val Leu Asp Gly Leu
1 5
<210> 49
<211> 13
<212> PRT
<213> 智人(Homo sapiens)
<400> 49
Cys Ala Val Lys Trp Thr Gly Gly Phe Lys Thr Ile Phe
1 5 10
<210> 50
<211> 5
<212> PRT
<213> 智人(Homo sapiens)
<400> 50
Met Asn His Glu Tyr
1 5
<210> 51
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 51
Ser Val Gly Ala Gly Ile
1 5
<210> 52
<211> 14
<212> PRT
<213> 智人(Homo sapiens)
<400> 52
Cys Ala Ser Ser Tyr Arg Glu Ser His Tyr Gly Tyr Thr Phe
1 5 10
<210> 53
<211> 127
<212> PRT
<213> 智人(Homo sapiens)
<400> 53
Met Trp Gly Val Phe Leu Leu Tyr Val Ser Met Lys Met Gly Gly Thr
1 5 10 15
Thr Gly Gln Asn Ile Asp Gln Pro Thr Glu Met Thr Ala Thr Glu Gly
20 25 30
Ala Ile Val Gln Ile Asn Cys Thr Tyr Gln Thr Ser Gly Phe Asn Gly
35 40 45
Leu Phe Trp Tyr Gln Gln His Ala Gly Glu Ala Pro Thr Phe Leu Ser
50 55 60
Tyr Asn Val Leu Asp Gly Leu Glu Glu Lys Gly Arg Phe Ser Ser Phe
65 70 75 80
Leu Ser Arg Ser Lys Gly Tyr Ser Tyr Leu Leu Leu Lys Glu Leu Gln
85 90 95
Met Lys Asp Ser Ala Ser Tyr Leu Cys Ala Val Lys Trp Thr Gly Gly
100 105 110
Phe Lys Thr Ile Phe Gly Ala Gly Thr Arg Leu Phe Val Lys Ala
115 120 125
<210> 54
<211> 134
<212> PRT
<213> 智人(Homo sapiens)
<400> 54
Met Ala Met Ser Ile Gly Leu Leu Cys Cys Ala Ala Leu Ser Leu Leu
1 5 10 15
Trp Ala Gly Pro Val Asn Ala Gly Val Thr Gln Thr Pro Lys Phe Gln
20 25 30
Val Leu Lys Thr Gly Gln Ser Met Thr Leu Gln Cys Ala Gln Asp Met
35 40 45
Asn His Glu Tyr Met Ser Trp Tyr Arg Gln Asp Pro Gly Met Gly Leu
50 55 60
Arg Leu Ile His Tyr Ser Val Gly Ala Gly Ile Thr Asp Gln Gly Glu
65 70 75 80
Val Pro Asn Gly Tyr Asn Val Ser Arg Ser Thr Thr Glu Asp Phe Pro
85 90 95
Leu Arg Leu Leu Ser Ala Ala Pro Ser Gln Thr Ser Val Tyr Phe Cys
100 105 110
Ala Ser Ser Tyr Arg Glu Ser His Tyr Gly Tyr Thr Phe Gly Ser Gly
115 120 125
Thr Arg Leu Thr Val Val
130
<210> 55
<211> 264
<212> PRT
<213> 智人(Homo sapiens)
<400> 55
Met Trp Gly Val Phe Leu Leu Tyr Val Ser Met Lys Met Gly Gly Thr
1 5 10 15
Thr Gly Gln Asn Ile Asp Gln Pro Thr Glu Met Thr Ala Thr Glu Gly
20 25 30
Ala Ile Val Gln Ile Asn Cys Thr Tyr Gln Thr Ser Gly Phe Asn Gly
35 40 45
Leu Phe Trp Tyr Gln Gln His Ala Gly Glu Ala Pro Thr Phe Leu Ser
50 55 60
Tyr Asn Val Leu Asp Gly Leu Glu Glu Lys Gly Arg Phe Ser Ser Phe
65 70 75 80
Leu Ser Arg Ser Lys Gly Tyr Ser Tyr Leu Leu Leu Lys Glu Leu Gln
85 90 95
Met Lys Asp Ser Ala Ser Tyr Leu Cys Ala Val Lys Trp Thr Gly Gly
100 105 110
Phe Lys Thr Ile Phe Gly Ala Gly Thr Arg Leu Phe Val Lys Ala Asn
115 120 125
Ile Gln Asn Pro Glu Pro Ala Val Tyr Gln Leu Lys Asp Pro Arg Ser
130 135 140
Gln Asp Ser Thr Leu Cys Leu Phe Thr Asp Phe Asp Ser Gln Ile Asn
145 150 155 160
Val Pro Lys Thr Met Glu Ser Gly Thr Phe Ile Thr Asp Lys Cys Val
165 170 175
Leu Asp Met Lys Ala Met Asp Ser Lys Ser Asn Gly Ala Ile Ala Trp
180 185 190
Ser Asn Gln Thr Ser Phe Thr Cys Gln Asp Ile Phe Lys Glu Thr Asn
195 200 205
Ala Thr Tyr Pro Ser Ser Asp Val Pro Cys Asp Ala Thr Leu Thr Glu
210 215 220
Lys Ser Phe Glu Thr Asp Met Asn Leu Asn Phe Gln Asn Leu Leu Val
225 230 235 240
Ile Val Leu Arg Ile Leu Leu Leu Lys Val Ala Gly Phe Asn Leu Leu
245 250 255
Met Thr Leu Arg Leu Trp Ser Ser
260
<210> 56
<211> 307
<212> PRT
<213> 智人(Homo sapiens)
<400> 56
Met Ala Met Ser Ile Gly Leu Leu Cys Cys Ala Ala Leu Ser Leu Leu
1 5 10 15
Trp Ala Gly Pro Val Asn Ala Gly Val Thr Gln Thr Pro Lys Phe Gln
20 25 30
Val Leu Lys Thr Gly Gln Ser Met Thr Leu Gln Cys Ala Gln Asp Met
35 40 45
Asn His Glu Tyr Met Ser Trp Tyr Arg Gln Asp Pro Gly Met Gly Leu
50 55 60
Arg Leu Ile His Tyr Ser Val Gly Ala Gly Ile Thr Asp Gln Gly Glu
65 70 75 80
Val Pro Asn Gly Tyr Asn Val Ser Arg Ser Thr Thr Glu Asp Phe Pro
85 90 95
Leu Arg Leu Leu Ser Ala Ala Pro Ser Gln Thr Ser Val Tyr Phe Cys
100 105 110
Ala Ser Ser Tyr Arg Glu Ser His Tyr Gly Tyr Thr Phe Gly Ser Gly
115 120 125
Thr Arg Leu Thr Val Val Glu Asp Leu Arg Asn Val Thr Pro Pro Lys
130 135 140
Val Ser Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys
145 150 155 160
Ala Thr Leu Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu
165 170 175
Leu Ser Trp Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr
180 185 190
Asp Pro Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser
195 200 205
Arg Leu Arg Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe
210 215 220
Arg Cys Gln Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro
225 230 235 240
Glu Gly Ser Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp
245 250 255
Gly Arg Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val
260 265 270
Leu Ser Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu
275 280 285
Tyr Ala Val Leu Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg
290 295 300
Lys Asn Ser
305
<210> 57
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 57
Val Ser Gly Asn Pro Tyr
1 5
<210> 58
<211> 8
<212> PRT
<213> 智人(Homo sapiens)
<400> 58
Tyr Ile Thr Gly Asp Asn Leu Val
1 5
<210> 59
<211> 12
<212> PRT
<213> 智人(Homo sapiens)
<400> 59
Cys Ala Val Arg Val Trp Asp Tyr Lys Leu Ser Phe
1 5 10
<210> 60
<211> 5
<212> PRT
<213> 智人(Homo sapiens)
<400> 60
Leu Asn His Asp Ala
1 5
<210> 61
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 61
Ser Gln Ile Val Asn Asp
1 5
<210> 62
<211> 14
<212> PRT
<213> 智人(Homo sapiens)
<400> 62
Cys Ala Ser Ser Ile Ser Ala Gly Gly Asp Gly Tyr Thr Phe
1 5 10
<210> 63
<211> 131
<212> PRT
<213> 智人(Homo sapiens)
<400> 63
Met Ala Ser Ala Pro Ile Ser Met Leu Ala Met Leu Phe Thr Leu Ser
1 5 10 15
Gly Leu Arg Ala Gln Ser Val Ala Gln Pro Glu Asp Gln Val Asn Val
20 25 30
Ala Glu Gly Asn Pro Leu Thr Val Lys Cys Thr Tyr Ser Val Ser Gly
35 40 45
Asn Pro Tyr Leu Phe Trp Tyr Val Gln Tyr Pro Asn Arg Gly Leu Gln
50 55 60
Phe Leu Leu Lys Tyr Ile Thr Gly Asp Asn Leu Val Lys Gly Ser Tyr
65 70 75 80
Gly Phe Glu Ala Glu Phe Asn Lys Ser Gln Thr Ser Phe His Leu Lys
85 90 95
Lys Pro Ser Ala Leu Val Ser Asp Ser Ala Leu Tyr Phe Cys Ala Val
100 105 110
Arg Val Trp Asp Tyr Lys Leu Ser Phe Gly Ala Gly Thr Thr Val Thr
115 120 125
Val Arg Ala
130
<210> 64
<211> 132
<212> PRT
<213> 智人(Homo sapiens)
<400> 64
Met His Asn Gln Val Leu Cys Cys Val Val Leu Cys Phe Leu Gly Ala
1 5 10 15
Asn Thr Val Asp Gly Gly Ile Thr Gln Ser Pro Lys Tyr Leu Phe Arg
20 25 30
Lys Glu Gly Gln Asn Val Thr Leu Ser Cys Glu Gln Asn Leu Asn His
35 40 45
Asp Ala Met Tyr Trp Tyr Arg Gln Asp Pro Gly Gln Gly Leu Arg Leu
50 55 60
Ile Tyr Tyr Ser Gln Ile Val Asn Asp Phe Gln Lys Gly Asp Ile Ala
65 70 75 80
Glu Gly Tyr Ser Val Ser Arg Glu Lys Lys Glu Ser Phe Pro Leu Thr
85 90 95
Val Thr Ser Ala Gln Lys Asn Pro Thr Ala Phe Tyr Leu Cys Ala Ser
100 105 110
Ser Ile Ser Ala Gly Gly Asp Gly Tyr Thr Phe Gly Ser Gly Thr Arg
115 120 125
Leu Thr Val Val
130
<210> 65
<211> 268
<212> PRT
<213> 智人(Homo sapiens)
<400> 65
Met Ala Ser Ala Pro Ile Ser Met Leu Ala Met Leu Phe Thr Leu Ser
1 5 10 15
Gly Leu Arg Ala Gln Ser Val Ala Gln Pro Glu Asp Gln Val Asn Val
20 25 30
Ala Glu Gly Asn Pro Leu Thr Val Lys Cys Thr Tyr Ser Val Ser Gly
35 40 45
Asn Pro Tyr Leu Phe Trp Tyr Val Gln Tyr Pro Asn Arg Gly Leu Gln
50 55 60
Phe Leu Leu Lys Tyr Ile Thr Gly Asp Asn Leu Val Lys Gly Ser Tyr
65 70 75 80
Gly Phe Glu Ala Glu Phe Asn Lys Ser Gln Thr Ser Phe His Leu Lys
85 90 95
Lys Pro Ser Ala Leu Val Ser Asp Ser Ala Leu Tyr Phe Cys Ala Val
100 105 110
Arg Val Trp Asp Tyr Lys Leu Ser Phe Gly Ala Gly Thr Thr Val Thr
115 120 125
Val Arg Ala Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr Gln Leu Lys
130 135 140
Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr Asp Phe Asp
145 150 155 160
Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr Phe Ile Thr
165 170 175
Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys Ser Asn Gly
180 185 190
Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln Asp Ile Phe
195 200 205
Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro Cys Asp Ala
210 215 220
Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu Asn Phe Gln
225 230 235 240
Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys Val Ala Gly
245 250 255
Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser
260 265
<210> 66
<211> 305
<212> PRT
<213> 智人(Homo sapiens)
<400> 66
Met His Asn Gln Val Leu Cys Cys Val Val Leu Cys Phe Leu Gly Ala
1 5 10 15
Asn Thr Val Asp Gly Gly Ile Thr Gln Ser Pro Lys Tyr Leu Phe Arg
20 25 30
Lys Glu Gly Gln Asn Val Thr Leu Ser Cys Glu Gln Asn Leu Asn His
35 40 45
Asp Ala Met Tyr Trp Tyr Arg Gln Asp Pro Gly Gln Gly Leu Arg Leu
50 55 60
Ile Tyr Tyr Ser Gln Ile Val Asn Asp Phe Gln Lys Gly Asp Ile Ala
65 70 75 80
Glu Gly Tyr Ser Val Ser Arg Glu Lys Lys Glu Ser Phe Pro Leu Thr
85 90 95
Val Thr Ser Ala Gln Lys Asn Pro Thr Ala Phe Tyr Leu Cys Ala Ser
100 105 110
Ser Ile Ser Ala Gly Gly Asp Gly Tyr Thr Phe Gly Ser Gly Thr Arg
115 120 125
Leu Thr Val Val Glu Asp Leu Arg Asn Val Thr Pro Pro Lys Val Ser
130 135 140
Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys Ala Thr
145 150 155 160
Leu Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu Leu Ser
165 170 175
Trp Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr Asp Pro
180 185 190
Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser Arg Leu
195 200 205
Arg Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe Arg Cys
210 215 220
Gln Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro Glu Gly
225 230 235 240
Ser Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp Gly Arg
245 250 255
Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val Leu Ser
260 265 270
Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu Tyr Ala
275 280 285
Val Leu Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg Lys Asn
290 295 300
Ser
305
<210> 67
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 67
Asn Ser Ala Ser Gln Ser
1 5
<210> 68
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 68
Val Tyr Ser Ser Gly Asn
1 5
<210> 69
<211> 13
<212> PRT
<213> 智人(Homo sapiens)
<400> 69
Cys Val Val Gln Pro Gly Gly Tyr Gln Lys Val Thr Phe
1 5 10
<210> 70
<211> 5
<212> PRT
<213> 智人(Homo sapiens)
<400> 70
Met Asn His Asn Ser
1 5
<210> 71
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 71
Ser Ala Ser Glu Gly Thr
1 5
<210> 72
<211> 16
<212> PRT
<213> 智人(Homo sapiens)
<400> 72
Cys Ala Ser Ser Glu Gly Leu Trp Gln Val Gly Asp Glu Gln Tyr Phe
1 5 10 15
<210> 73
<211> 131
<212> PRT
<213> 智人(Homo sapiens)
<400> 73
Met Ile Ser Leu Arg Val Leu Leu Val Ile Leu Trp Leu Gln Leu Ser
1 5 10 15
Trp Val Trp Ser Gln Arg Lys Glu Val Glu Gln Asp Pro Gly Pro Phe
20 25 30
Asn Val Pro Glu Gly Ala Thr Val Ala Phe Asn Cys Thr Tyr Ser Asn
35 40 45
Ser Ala Ser Gln Ser Phe Phe Trp Tyr Arg Gln Asp Cys Arg Lys Glu
50 55 60
Pro Lys Leu Leu Met Ser Val Tyr Ser Ser Gly Asn Glu Asp Gly Arg
65 70 75 80
Phe Thr Ala Gln Leu Asn Arg Ala Ser Gln Tyr Ile Ser Leu Leu Ile
85 90 95
Arg Asp Ser Lys Leu Ser Asp Ser Ala Thr Tyr Leu Cys Val Val Gln
100 105 110
Pro Gly Gly Tyr Gln Lys Val Thr Phe Gly Thr Gly Thr Lys Leu Gln
115 120 125
Val Ile Pro
130
<210> 74
<211> 134
<212> PRT
<213> 智人(Homo sapiens)
<400> 74
Met Ala Ile Gly Leu Leu Cys Cys Val Ala Phe Ser Leu Leu Trp Ala
1 5 10 15
Ser Pro Val Asn Ala Gly Val Thr Gln Thr Pro Lys Phe Gln Val Leu
20 25 30
Lys Thr Gly Gln Ser Met Thr Leu Gln Cys Ala Gln Asp Met Asn His
35 40 45
Asn Ser Met Tyr Trp Tyr Arg Gln Asp Pro Gly Met Gly Leu Arg Leu
50 55 60
Ile Tyr Tyr Ser Ala Ser Glu Gly Thr Thr Asp Lys Gly Glu Val Pro
65 70 75 80
Asn Gly Tyr Asn Val Ser Arg Leu Asn Lys Arg Glu Phe Ser Leu Arg
85 90 95
Leu Glu Ser Ala Ala Pro Ser Gln Thr Ser Val Tyr Phe Cys Ala Ser
100 105 110
Ser Glu Gly Leu Trp Gln Val Gly Asp Glu Gln Tyr Phe Gly Pro Gly
115 120 125
Thr Arg Leu Thr Val Thr
130
<210> 75
<211> 268
<212> PRT
<213> 智人(Homo sapiens)
<400> 75
Met Ile Ser Leu Arg Val Leu Leu Val Ile Leu Trp Leu Gln Leu Ser
1 5 10 15
Trp Val Trp Ser Gln Arg Lys Glu Val Glu Gln Asp Pro Gly Pro Phe
20 25 30
Asn Val Pro Glu Gly Ala Thr Val Ala Phe Asn Cys Thr Tyr Ser Asn
35 40 45
Ser Ala Ser Gln Ser Phe Phe Trp Tyr Arg Gln Asp Cys Arg Lys Glu
50 55 60
Pro Lys Leu Leu Met Ser Val Tyr Ser Ser Gly Asn Glu Asp Gly Arg
65 70 75 80
Phe Thr Ala Gln Leu Asn Arg Ala Ser Gln Tyr Ile Ser Leu Leu Ile
85 90 95
Arg Asp Ser Lys Leu Ser Asp Ser Ala Thr Tyr Leu Cys Val Val Gln
100 105 110
Pro Gly Gly Tyr Gln Lys Val Thr Phe Gly Thr Gly Thr Lys Leu Gln
115 120 125
Val Ile Pro Asp Ile Gln Asn Pro Glu Pro Ala Val Tyr Gln Leu Lys
130 135 140
Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr Asp Phe Asp
145 150 155 160
Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr Phe Ile Thr
165 170 175
Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys Ser Asn Gly
180 185 190
Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln Asp Ile Phe
195 200 205
Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro Cys Asp Ala
210 215 220
Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu Asn Phe Gln
225 230 235 240
Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys Val Ala Gly
245 250 255
Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser
260 265
<210> 76
<211> 307
<212> PRT
<213> 智人(Homo sapiens)
<400> 76
Met Ala Ile Gly Leu Leu Cys Cys Val Ala Phe Ser Leu Leu Trp Ala
1 5 10 15
Ser Pro Val Asn Ala Gly Val Thr Gln Thr Pro Lys Phe Gln Val Leu
20 25 30
Lys Thr Gly Gln Ser Met Thr Leu Gln Cys Ala Gln Asp Met Asn His
35 40 45
Asn Ser Met Tyr Trp Tyr Arg Gln Asp Pro Gly Met Gly Leu Arg Leu
50 55 60
Ile Tyr Tyr Ser Ala Ser Glu Gly Thr Thr Asp Lys Gly Glu Val Pro
65 70 75 80
Asn Gly Tyr Asn Val Ser Arg Leu Asn Lys Arg Glu Phe Ser Leu Arg
85 90 95
Leu Glu Ser Ala Ala Pro Ser Gln Thr Ser Val Tyr Phe Cys Ala Ser
100 105 110
Ser Glu Gly Leu Trp Gln Val Gly Asp Glu Gln Tyr Phe Gly Pro Gly
115 120 125
Thr Arg Leu Thr Val Thr Glu Asp Leu Arg Asn Val Thr Pro Pro Lys
130 135 140
Val Ser Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys
145 150 155 160
Ala Thr Leu Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu
165 170 175
Leu Ser Trp Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr
180 185 190
Asp Pro Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser
195 200 205
Arg Leu Arg Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe
210 215 220
Arg Cys Gln Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro
225 230 235 240
Glu Gly Ser Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp
245 250 255
Gly Arg Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val
260 265 270
Leu Ser Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu
275 280 285
Tyr Ala Val Leu Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg
290 295 300
Lys Asn Ser
305
<210> 77
<211> 7
<212> PRT
<213> 智人(Homo sapiens)
<400> 77
Thr Ser Glu Asn Asn Tyr Tyr
1 5
<210> 78
<211> 8
<212> PRT
<213> 智人(Homo sapiens)
<400> 78
Gln Glu Ala Tyr Lys Gln Gln Asn
1 5
<210> 79
<211> 16
<212> PRT
<213> 智人(Homo sapiens)
<400> 79
Cys Ala Phe Met Gly Tyr Ser Gly Ala Gly Ser Tyr Gln Leu Thr Phe
1 5 10 15
<210> 80
<211> 5
<212> PRT
<213> 智人(Homo sapiens)
<400> 80
Glu Asn His Arg Tyr
1 5
<210> 81
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 81
Ser Tyr Gly Val Lys Asp
1 5
<210> 82
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 82
Cys Ala Ile Ser Glu Leu Val Thr Gly Asp Ser Pro Leu His Phe
1 5 10 15
<210> 83
<211> 137
<212> PRT
<213> 智人(Homo sapiens)
<400> 83
Met Thr Arg Val Ser Leu Leu Trp Ala Val Val Val Ser Thr Cys Leu
1 5 10 15
Glu Ser Gly Met Ala Gln Thr Val Thr Gln Ser Gln Pro Glu Met Ser
20 25 30
Val Gln Glu Ala Glu Thr Val Thr Leu Ser Cys Thr Tyr Asp Thr Ser
35 40 45
Glu Asn Asn Tyr Tyr Leu Phe Trp Tyr Lys Gln Pro Pro Ser Arg Gln
50 55 60
Met Ile Leu Val Ile Arg Gln Glu Ala Tyr Lys Gln Gln Asn Ala Thr
65 70 75 80
Glu Asn Arg Phe Ser Val Asn Phe Gln Lys Ala Ala Lys Ser Phe Ser
85 90 95
Leu Lys Ile Ser Asp Ser Gln Leu Gly Asp Thr Ala Met Tyr Phe Cys
100 105 110
Ala Phe Met Gly Tyr Ser Gly Ala Gly Ser Tyr Gln Leu Thr Phe Gly
115 120 125
Lys Gly Thr Lys Leu Ser Val Ile Pro
130 135
<210> 84
<211> 133
<212> PRT
<213> 智人(Homo sapiens)
<400> 84
Met Ala Thr Arg Leu Phe Phe Tyr Val Ala Leu Cys Leu Leu Trp Thr
1 5 10 15
Gly His Met Asp Ala Gly Ile Thr Gln Ser Pro Arg His Lys Val Thr
20 25 30
Glu Thr Gly Thr Pro Val Thr Leu Arg Cys His Gln Thr Glu Asn His
35 40 45
Arg Tyr Met Tyr Trp Tyr Arg Gln Asp Pro Gly His Gly Leu Arg Leu
50 55 60
Ile His Tyr Ser Tyr Gly Val Lys Asp Thr Asp Lys Gly Glu Val Ser
65 70 75 80
Asp Gly Tyr Ser Val Ser Arg Ser Lys Thr Glu Asp Phe Leu Leu Thr
85 90 95
Leu Glu Ser Ala Thr Ser Ser Gln Thr Ser Val Tyr Phe Cys Ala Ile
100 105 110
Ser Glu Leu Val Thr Gly Asp Ser Pro Leu His Phe Gly Asn Gly Thr
115 120 125
Arg Leu Thr Val Thr
130
<210> 85
<211> 274
<212> PRT
<213> 智人(Homo sapiens)
<400> 85
Met Thr Arg Val Ser Leu Leu Trp Ala Val Val Val Ser Thr Cys Leu
1 5 10 15
Glu Ser Gly Met Ala Gln Thr Val Thr Gln Ser Gln Pro Glu Met Ser
20 25 30
Val Gln Glu Ala Glu Thr Val Thr Leu Ser Cys Thr Tyr Asp Thr Ser
35 40 45
Glu Asn Asn Tyr Tyr Leu Phe Trp Tyr Lys Gln Pro Pro Ser Arg Gln
50 55 60
Met Ile Leu Val Ile Arg Gln Glu Ala Tyr Lys Gln Gln Asn Ala Thr
65 70 75 80
Glu Asn Arg Phe Ser Val Asn Phe Gln Lys Ala Ala Lys Ser Phe Ser
85 90 95
Leu Lys Ile Ser Asp Ser Gln Leu Gly Asp Thr Ala Met Tyr Phe Cys
100 105 110
Ala Phe Met Gly Tyr Ser Gly Ala Gly Ser Tyr Gln Leu Thr Phe Gly
115 120 125
Lys Gly Thr Lys Leu Ser Val Ile Pro Asp Ile Gln Asn Pro Glu Pro
130 135 140
Ala Val Tyr Gln Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys
145 150 155 160
Leu Phe Thr Asp Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu
165 170 175
Ser Gly Thr Phe Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met
180 185 190
Asp Ser Lys Ser Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe
195 200 205
Thr Cys Gln Asp Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser
210 215 220
Asp Val Pro Cys Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp
225 230 235 240
Met Asn Leu Asn Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu
245 250 255
Leu Leu Lys Val Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp
260 265 270
Ser Ser
<210> 86
<211> 306
<212> PRT
<213> 智人(Homo sapiens)
<400> 86
Met Ala Thr Arg Leu Phe Phe Tyr Val Ala Leu Cys Leu Leu Trp Thr
1 5 10 15
Gly His Met Asp Ala Gly Ile Thr Gln Ser Pro Arg His Lys Val Thr
20 25 30
Glu Thr Gly Thr Pro Val Thr Leu Arg Cys His Gln Thr Glu Asn His
35 40 45
Arg Tyr Met Tyr Trp Tyr Arg Gln Asp Pro Gly His Gly Leu Arg Leu
50 55 60
Ile His Tyr Ser Tyr Gly Val Lys Asp Thr Asp Lys Gly Glu Val Ser
65 70 75 80
Asp Gly Tyr Ser Val Ser Arg Ser Lys Thr Glu Asp Phe Leu Leu Thr
85 90 95
Leu Glu Ser Ala Thr Ser Ser Gln Thr Ser Val Tyr Phe Cys Ala Ile
100 105 110
Ser Glu Leu Val Thr Gly Asp Ser Pro Leu His Phe Gly Asn Gly Thr
115 120 125
Arg Leu Thr Val Thr Glu Asp Leu Arg Asn Val Thr Pro Pro Lys Val
130 135 140
Ser Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys Ala
145 150 155 160
Thr Leu Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu Leu
165 170 175
Ser Trp Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr Asp
180 185 190
Pro Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser Arg
195 200 205
Leu Arg Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe Arg
210 215 220
Cys Gln Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro Glu
225 230 235 240
Gly Ser Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp Gly
245 250 255
Arg Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val Leu
260 265 270
Ser Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu Tyr
275 280 285
Ala Val Leu Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg Lys
290 295 300
Asn Ser
305
<210> 87
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 87
Asn Tyr Ser Pro Ala Tyr
1 5
<210> 88
<211> 7
<212> PRT
<213> 智人(Homo sapiens)
<400> 88
Ile Arg Glu Asn Glu Lys Glu
1 5
<210> 89
<211> 12
<212> PRT
<213> 智人(Homo sapiens)
<400> 89
Cys Ala Leu Asp Ile Tyr Pro His Asp Met Arg Phe
1 5 10
<210> 90
<211> 5
<212> PRT
<213> 智人(Homo sapiens)
<400> 90
Ser Gly His Ala Thr
1 5
<210> 91
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 91
Phe Gln Asn Asn Gly Val
1 5
<210> 92
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 92
Cys Ala Ser Ser Leu Asp Pro Gly Asp Thr Gly Glu Leu Phe Phe
1 5 10 15
<210> 93
<211> 131
<212> PRT
<213> 智人(Homo sapiens)
<400> 93
Met Glu Ser Phe Leu Gly Gly Val Leu Leu Ile Leu Trp Leu Gln Val
1 5 10 15
Asp Trp Val Lys Ser Gln Lys Ile Glu Gln Asn Ser Glu Ala Leu Asn
20 25 30
Ile Gln Glu Gly Lys Thr Ala Thr Leu Thr Cys Asn Tyr Thr Asn Tyr
35 40 45
Ser Pro Ala Tyr Leu Gln Trp Tyr Arg Gln Asp Pro Gly Arg Gly Pro
50 55 60
Val Phe Leu Leu Leu Ile Arg Glu Asn Glu Lys Glu Lys Arg Lys Glu
65 70 75 80
Arg Leu Lys Val Thr Phe Asp Thr Thr Leu Lys Gln Ser Leu Phe His
85 90 95
Ile Thr Ala Ser Gln Pro Ala Asp Ser Ala Thr Tyr Leu Cys Ala Leu
100 105 110
Asp Ile Tyr Pro His Asp Met Arg Phe Gly Ala Gly Thr Arg Leu Thr
115 120 125
Val Lys Pro
130
<210> 94
<211> 134
<212> PRT
<213> 智人(Homo sapiens)
<400> 94
Met Ala Thr Arg Leu Leu Cys Trp Ala Ala Leu Cys Leu Leu Gly Ala
1 5 10 15
Glu Leu Thr Glu Ala Gly Val Ala Gln Ser Pro Arg Tyr Lys Ile Ile
20 25 30
Glu Lys Arg Gln Ser Val Ala Phe Trp Cys Asn Pro Ile Ser Gly His
35 40 45
Ala Thr Leu Tyr Trp Tyr Gln Gln Ile Leu Gly Gln Gly Pro Lys Leu
50 55 60
Leu Ile Gln Phe Gln Asn Asn Gly Val Val Asp Asp Ser Gln Leu Pro
65 70 75 80
Lys Asp Arg Phe Ser Ala Glu Arg Leu Lys Gly Val Asp Ser Thr Leu
85 90 95
Lys Ile Gln Pro Ala Lys Leu Glu Asp Ser Ala Val Tyr Leu Cys Ala
100 105 110
Ser Ser Leu Asp Pro Gly Asp Thr Gly Glu Leu Phe Phe Gly Glu Gly
115 120 125
Ser Arg Leu Thr Val Leu
130
<210> 95
<211> 268
<212> PRT
<213> 智人(Homo sapiens)
<400> 95
Met Glu Ser Phe Leu Gly Gly Val Leu Leu Ile Leu Trp Leu Gln Val
1 5 10 15
Asp Trp Val Lys Ser Gln Lys Ile Glu Gln Asn Ser Glu Ala Leu Asn
20 25 30
Ile Gln Glu Gly Lys Thr Ala Thr Leu Thr Cys Asn Tyr Thr Asn Tyr
35 40 45
Ser Pro Ala Tyr Leu Gln Trp Tyr Arg Gln Asp Pro Gly Arg Gly Pro
50 55 60
Val Phe Leu Leu Leu Ile Arg Glu Asn Glu Lys Glu Lys Arg Lys Glu
65 70 75 80
Arg Leu Lys Val Thr Phe Asp Thr Thr Leu Lys Gln Ser Leu Phe His
85 90 95
Ile Thr Ala Ser Gln Pro Ala Asp Ser Ala Thr Tyr Leu Cys Ala Leu
100 105 110
Asp Ile Tyr Pro His Asp Met Arg Phe Gly Ala Gly Thr Arg Leu Thr
115 120 125
Val Lys Pro Asp Ile Gln Asn Pro Glu Pro Ala Val Tyr Gln Leu Lys
130 135 140
Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr Asp Phe Asp
145 150 155 160
Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr Phe Ile Thr
165 170 175
Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys Ser Asn Gly
180 185 190
Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln Asp Ile Phe
195 200 205
Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro Cys Asp Ala
210 215 220
Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu Asn Phe Gln
225 230 235 240
Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys Val Ala Gly
245 250 255
Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser
260 265
<210> 96
<211> 307
<212> PRT
<213> 智人(Homo sapiens)
<400> 96
Met Ala Thr Arg Leu Leu Cys Trp Ala Ala Leu Cys Leu Leu Gly Ala
1 5 10 15
Glu Leu Thr Glu Ala Gly Val Ala Gln Ser Pro Arg Tyr Lys Ile Ile
20 25 30
Glu Lys Arg Gln Ser Val Ala Phe Trp Cys Asn Pro Ile Ser Gly His
35 40 45
Ala Thr Leu Tyr Trp Tyr Gln Gln Ile Leu Gly Gln Gly Pro Lys Leu
50 55 60
Leu Ile Gln Phe Gln Asn Asn Gly Val Val Asp Asp Ser Gln Leu Pro
65 70 75 80
Lys Asp Arg Phe Ser Ala Glu Arg Leu Lys Gly Val Asp Ser Thr Leu
85 90 95
Lys Ile Gln Pro Ala Lys Leu Glu Asp Ser Ala Val Tyr Leu Cys Ala
100 105 110
Ser Ser Leu Asp Pro Gly Asp Thr Gly Glu Leu Phe Phe Gly Glu Gly
115 120 125
Ser Arg Leu Thr Val Leu Glu Asp Leu Arg Asn Val Thr Pro Pro Lys
130 135 140
Val Ser Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys
145 150 155 160
Ala Thr Leu Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu
165 170 175
Leu Ser Trp Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr
180 185 190
Asp Pro Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser
195 200 205
Arg Leu Arg Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe
210 215 220
Arg Cys Gln Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro
225 230 235 240
Glu Gly Ser Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp
245 250 255
Gly Arg Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val
260 265 270
Leu Ser Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu
275 280 285
Tyr Ala Val Leu Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg
290 295 300
Lys Asn Ser
305
<210> 97
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 97
Ser Ser Val Ser Val Tyr
1 5
<210> 98
<211> 8
<212> PRT
<213> 智人(Homo sapiens)
<400> 98
Tyr Leu Ser Gly Ser Thr Leu Val
1 5
<210> 99
<211> 14
<212> PRT
<213> 智人(Homo sapiens)
<400> 99
Cys Ala Val Ser Asp Leu Val Arg Asp Asp Lys Ile Ile Phe
1 5 10
<210> 100
<211> 5
<212> PRT
<213> 智人(Homo sapiens)
<400> 100
Met Asn His Asn Ser
1 5
<210> 101
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 101
Ser Ala Ser Glu Gly Thr
1 5
<210> 102
<211> 11
<212> PRT
<213> 智人(Homo sapiens)
<400> 102
Cys Ala Ser Ile Gly Gly Phe Glu Ala Phe Phe
1 5 10
<210> 103
<211> 133
<212> PRT
<213> 智人(Homo sapiens)
<400> 103
Met Ala Leu Leu Leu Val Pro Ala Phe Gln Val Ile Phe Thr Leu Gly
1 5 10 15
Gly Thr Arg Ala Gln Ser Val Thr Gln Leu Asp Ser Gln Val Pro Val
20 25 30
Phe Glu Glu Ala Pro Val Glu Leu Arg Cys Asn Tyr Ser Ser Ser Val
35 40 45
Ser Val Tyr Leu Phe Trp Tyr Val Gln Tyr Pro Asn Gln Gly Leu Gln
50 55 60
Leu Leu Leu Lys Tyr Leu Ser Gly Ser Thr Leu Val Glu Ser Ile Asn
65 70 75 80
Gly Phe Glu Ala Glu Phe Asn Lys Ser Gln Thr Ser Phe His Leu Arg
85 90 95
Lys Pro Ser Val His Ile Ser Asp Thr Ala Glu Tyr Phe Cys Ala Val
100 105 110
Ser Asp Leu Val Arg Asp Asp Lys Ile Ile Phe Gly Lys Gly Thr Arg
115 120 125
Leu His Ile Leu Pro
130
<210> 104
<211> 129
<212> PRT
<213> 智人(Homo sapiens)
<400> 104
Met His Ile Gly Leu Leu Cys Cys Val Ala Phe Ser Leu Leu Trp Ala
1 5 10 15
Ser Pro Val Asn Ala Gly Val Thr Gln Thr Pro Lys Phe Gln Val Leu
20 25 30
Lys Thr Gly Gln Ser Met Thr Leu Gln Cys Ala Gln Asp Met Asn His
35 40 45
Asn Ser Met Tyr Trp Tyr Arg Gln Asp Pro Gly Met Gly Leu Arg Leu
50 55 60
Ile Tyr Tyr Ser Ala Ser Glu Gly Thr Thr Asp Lys Gly Glu Val Pro
65 70 75 80
Asn Gly Tyr Asn Val Ser Arg Leu Asn Lys Arg Glu Phe Ser Leu Arg
85 90 95
Leu Glu Ser Ala Ala Pro Ser Gln Thr Ser Val Tyr Phe Cys Ala Ser
100 105 110
Ile Gly Gly Phe Glu Ala Phe Phe Gly Gln Gly Thr Arg Leu Thr Val
115 120 125
Val
<210> 105
<211> 270
<212> PRT
<213> 智人(Homo sapiens)
<400> 105
Met Ala Leu Leu Leu Val Pro Ala Phe Gln Val Ile Phe Thr Leu Gly
1 5 10 15
Gly Thr Arg Ala Gln Ser Val Thr Gln Leu Asp Ser Gln Val Pro Val
20 25 30
Phe Glu Glu Ala Pro Val Glu Leu Arg Cys Asn Tyr Ser Ser Ser Val
35 40 45
Ser Val Tyr Leu Phe Trp Tyr Val Gln Tyr Pro Asn Gln Gly Leu Gln
50 55 60
Leu Leu Leu Lys Tyr Leu Ser Gly Ser Thr Leu Val Glu Ser Ile Asn
65 70 75 80
Gly Phe Glu Ala Glu Phe Asn Lys Ser Gln Thr Ser Phe His Leu Arg
85 90 95
Lys Pro Ser Val His Ile Ser Asp Thr Ala Glu Tyr Phe Cys Ala Val
100 105 110
Ser Asp Leu Val Arg Asp Asp Lys Ile Ile Phe Gly Lys Gly Thr Arg
115 120 125
Leu His Ile Leu Pro Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr Gln
130 135 140
Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr Asp
145 150 155 160
Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr Phe
165 170 175
Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys Ser
180 185 190
Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln Asp
195 200 205
Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro Cys
210 215 220
Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu Asn
225 230 235 240
Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys Val
245 250 255
Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser
260 265 270
<210> 106
<211> 302
<212> PRT
<213> 智人(Homo sapiens)
<400> 106
Met His Ile Gly Leu Leu Cys Cys Val Ala Phe Ser Leu Leu Trp Ala
1 5 10 15
Ser Pro Val Asn Ala Gly Val Thr Gln Thr Pro Lys Phe Gln Val Leu
20 25 30
Lys Thr Gly Gln Ser Met Thr Leu Gln Cys Ala Gln Asp Met Asn His
35 40 45
Asn Ser Met Tyr Trp Tyr Arg Gln Asp Pro Gly Met Gly Leu Arg Leu
50 55 60
Ile Tyr Tyr Ser Ala Ser Glu Gly Thr Thr Asp Lys Gly Glu Val Pro
65 70 75 80
Asn Gly Tyr Asn Val Ser Arg Leu Asn Lys Arg Glu Phe Ser Leu Arg
85 90 95
Leu Glu Ser Ala Ala Pro Ser Gln Thr Ser Val Tyr Phe Cys Ala Ser
100 105 110
Ile Gly Gly Phe Glu Ala Phe Phe Gly Gln Gly Thr Arg Leu Thr Val
115 120 125
Val Glu Asp Leu Arg Asn Val Thr Pro Pro Lys Val Ser Leu Phe Glu
130 135 140
Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys Ala Thr Leu Val Cys
145 150 155 160
Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu Leu Ser Trp Trp Val
165 170 175
Asn Gly Lys Glu Val His Ser Gly Val Cys Thr Asp Pro Gln Ala Tyr
180 185 190
Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser Arg Leu Arg Val Ser
195 200 205
Ala Thr Phe Trp His Asn Pro Arg Asn His Phe Arg Cys Gln Val Gln
210 215 220
Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro Glu Gly Ser Pro Lys
225 230 235 240
Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp Gly Arg Ala Asp Cys
245 250 255
Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val Leu Ser Ala Thr Ile
260 265 270
Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu Tyr Ala Val Leu Val
275 280 285
Ser Thr Leu Val Val Met Ala Met Val Lys Arg Lys Asn Ser
290 295 300
<210> 107
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 107
Thr Ser Gly Phe Asn Gly
1 5
<210> 108
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 108
Asn Val Leu Asp Gly Leu
1 5
<210> 109
<211> 12
<212> PRT
<213> 智人(Homo sapiens)
<400> 109
Cys Ala Val Tyr Thr Gly Gly Phe Lys Thr Ile Phe
1 5 10
<210> 110
<211> 5
<212> PRT
<213> 智人(Homo sapiens)
<400> 110
Ser Gly His Ala Thr
1 5
<210> 111
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 111
Phe Gln Asn Asn Gly Val
1 5
<210> 112
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 112
Cys Ala Ser Asn Leu Gly Gly Gly Ser Thr Asp Thr Gln Tyr Phe
1 5 10 15
<210> 113
<211> 126
<212> PRT
<213> 智人(Homo sapiens)
<400> 113
Met Ala Gly Val Phe Leu Leu Tyr Val Ser Met Lys Met Gly Gly Thr
1 5 10 15
Thr Gly Gln Asn Ile Asp Gln Pro Thr Glu Met Thr Ala Thr Glu Gly
20 25 30
Ala Ile Val Gln Ile Asn Cys Thr Tyr Gln Thr Ser Gly Phe Asn Gly
35 40 45
Leu Phe Trp Tyr Gln Gln His Ala Gly Glu Ala Pro Thr Phe Leu Ser
50 55 60
Tyr Asn Val Leu Asp Gly Leu Glu Glu Lys Gly Arg Phe Ser Ser Phe
65 70 75 80
Leu Ser Arg Ser Lys Gly Tyr Ser Tyr Leu Leu Leu Lys Glu Leu Gln
85 90 95
Met Lys Asp Ser Ala Ser Tyr Leu Cys Ala Val Tyr Thr Gly Gly Phe
100 105 110
Lys Thr Ile Phe Gly Ala Gly Thr Arg Leu Phe Val Lys Ala
115 120 125
<210> 114
<211> 134
<212> PRT
<213> 智人(Homo sapiens)
<400> 114
Met His Thr Arg Leu Leu Cys Trp Ala Ala Leu Cys Leu Leu Gly Ala
1 5 10 15
Glu Leu Thr Glu Ala Gly Val Ala Gln Ser Pro Arg Tyr Lys Ile Ile
20 25 30
Glu Lys Arg Gln Ser Val Ala Phe Trp Cys Asn Pro Ile Ser Gly His
35 40 45
Ala Thr Leu Tyr Trp Tyr Gln Gln Ile Leu Gly Gln Gly Pro Lys Leu
50 55 60
Leu Ile Gln Phe Gln Asn Asn Gly Val Val Asp Asp Ser Gln Leu Pro
65 70 75 80
Lys Asp Arg Phe Ser Ala Glu Arg Leu Lys Gly Val Asp Ser Thr Leu
85 90 95
Lys Ile Gln Pro Ala Lys Leu Glu Asp Ser Ala Val Tyr Leu Cys Ala
100 105 110
Ser Asn Leu Gly Gly Gly Ser Thr Asp Thr Gln Tyr Phe Gly Pro Gly
115 120 125
Thr Arg Leu Thr Val Leu
130
<210> 115
<211> 263
<212> PRT
<213> 智人(Homo sapiens)
<400> 115
Met Ala Gly Val Phe Leu Leu Tyr Val Ser Met Lys Met Gly Gly Thr
1 5 10 15
Thr Gly Gln Asn Ile Asp Gln Pro Thr Glu Met Thr Ala Thr Glu Gly
20 25 30
Ala Ile Val Gln Ile Asn Cys Thr Tyr Gln Thr Ser Gly Phe Asn Gly
35 40 45
Leu Phe Trp Tyr Gln Gln His Ala Gly Glu Ala Pro Thr Phe Leu Ser
50 55 60
Tyr Asn Val Leu Asp Gly Leu Glu Glu Lys Gly Arg Phe Ser Ser Phe
65 70 75 80
Leu Ser Arg Ser Lys Gly Tyr Ser Tyr Leu Leu Leu Lys Glu Leu Gln
85 90 95
Met Lys Asp Ser Ala Ser Tyr Leu Cys Ala Val Tyr Thr Gly Gly Phe
100 105 110
Lys Thr Ile Phe Gly Ala Gly Thr Arg Leu Phe Val Lys Ala Asn Ile
115 120 125
Gln Asn Pro Glu Pro Ala Val Tyr Gln Leu Lys Asp Pro Arg Ser Gln
130 135 140
Asp Ser Thr Leu Cys Leu Phe Thr Asp Phe Asp Ser Gln Ile Asn Val
145 150 155 160
Pro Lys Thr Met Glu Ser Gly Thr Phe Ile Thr Asp Lys Cys Val Leu
165 170 175
Asp Met Lys Ala Met Asp Ser Lys Ser Asn Gly Ala Ile Ala Trp Ser
180 185 190
Asn Gln Thr Ser Phe Thr Cys Gln Asp Ile Phe Lys Glu Thr Asn Ala
195 200 205
Thr Tyr Pro Ser Ser Asp Val Pro Cys Asp Ala Thr Leu Thr Glu Lys
210 215 220
Ser Phe Glu Thr Asp Met Asn Leu Asn Phe Gln Asn Leu Leu Val Ile
225 230 235 240
Val Leu Arg Ile Leu Leu Leu Lys Val Ala Gly Phe Asn Leu Leu Met
245 250 255
Thr Leu Arg Leu Trp Ser Ser
260
<210> 116
<211> 307
<212> PRT
<213> 智人(Homo sapiens)
<400> 116
Met His Thr Arg Leu Leu Cys Trp Ala Ala Leu Cys Leu Leu Gly Ala
1 5 10 15
Glu Leu Thr Glu Ala Gly Val Ala Gln Ser Pro Arg Tyr Lys Ile Ile
20 25 30
Glu Lys Arg Gln Ser Val Ala Phe Trp Cys Asn Pro Ile Ser Gly His
35 40 45
Ala Thr Leu Tyr Trp Tyr Gln Gln Ile Leu Gly Gln Gly Pro Lys Leu
50 55 60
Leu Ile Gln Phe Gln Asn Asn Gly Val Val Asp Asp Ser Gln Leu Pro
65 70 75 80
Lys Asp Arg Phe Ser Ala Glu Arg Leu Lys Gly Val Asp Ser Thr Leu
85 90 95
Lys Ile Gln Pro Ala Lys Leu Glu Asp Ser Ala Val Tyr Leu Cys Ala
100 105 110
Ser Asn Leu Gly Gly Gly Ser Thr Asp Thr Gln Tyr Phe Gly Pro Gly
115 120 125
Thr Arg Leu Thr Val Leu Glu Asp Leu Arg Asn Val Thr Pro Pro Lys
130 135 140
Val Ser Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys
145 150 155 160
Ala Thr Leu Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu
165 170 175
Leu Ser Trp Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr
180 185 190
Asp Pro Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser
195 200 205
Arg Leu Arg Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe
210 215 220
Arg Cys Gln Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro
225 230 235 240
Glu Gly Ser Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp
245 250 255
Gly Arg Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val
260 265 270
Leu Ser Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu
275 280 285
Tyr Ala Val Leu Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg
290 295 300
Lys Asn Ser
305
<210> 117
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 117
Thr Ser Gly Phe Asn Gly
1 5
<210> 118
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 118
Asn Val Leu Asp Gly Leu
1 5
<210> 119
<211> 14
<212> PRT
<213> 智人(Homo sapiens)
<400> 119
Cys Ala Phe Tyr Tyr Gly Gly Ser Gln Gly Asn Leu Ile Phe
1 5 10
<210> 120
<211> 5
<212> PRT
<213> 智人(Homo sapiens)
<400> 120
Ser Gly His Val Ser
1 5
<210> 121
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 121
Phe Gln Asn Glu Ala Gln
1 5
<210> 122
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 122
Cys Ala Ser Ser Phe Gly Ser Gly Ser Thr Asp Thr Gln Tyr Phe
1 5 10 15
<210> 123
<211> 128
<212> PRT
<213> 智人(Homo sapiens)
<400> 123
Met Ala Gly Val Phe Leu Leu Tyr Val Ser Met Lys Met Gly Gly Thr
1 5 10 15
Thr Gly Gln Asn Ile Asp Gln Pro Thr Glu Met Thr Ala Thr Glu Gly
20 25 30
Ala Ile Val Gln Ile Asn Cys Thr Tyr Gln Thr Ser Gly Phe Asn Gly
35 40 45
Leu Phe Trp Tyr Gln Gln His Ala Gly Glu Ala Pro Thr Phe Leu Ser
50 55 60
Tyr Asn Val Leu Asp Gly Leu Glu Glu Lys Gly Arg Phe Ser Ser Phe
65 70 75 80
Leu Ser Arg Ser Lys Gly Tyr Ser Tyr Leu Leu Leu Lys Glu Leu Gln
85 90 95
Met Lys Asp Ser Ala Ser Tyr Leu Cys Ala Phe Tyr Tyr Gly Gly Ser
100 105 110
Gln Gly Asn Leu Ile Phe Gly Lys Gly Thr Lys Leu Ser Val Lys Pro
115 120 125
<210> 124
<211> 134
<212> PRT
<213> 智人(Homo sapiens)
<400> 124
Met His Thr Arg Leu Leu Cys Trp Val Val Leu Gly Phe Leu Gly Thr
1 5 10 15
Asp His Thr Gly Ala Gly Val Ser Gln Ser Pro Arg Tyr Lys Val Ala
20 25 30
Lys Arg Gly Gln Asp Val Ala Leu Arg Cys Asp Pro Ile Ser Gly His
35 40 45
Val Ser Leu Phe Trp Tyr Gln Gln Ala Leu Gly Gln Gly Pro Glu Phe
50 55 60
Leu Thr Tyr Phe Gln Asn Glu Ala Gln Leu Asp Lys Ser Gly Leu Pro
65 70 75 80
Ser Asp Arg Phe Phe Ala Glu Arg Pro Glu Gly Ser Val Ser Thr Leu
85 90 95
Lys Ile Gln Arg Thr Gln Gln Glu Asp Ser Ala Val Tyr Leu Cys Ala
100 105 110
Ser Ser Phe Gly Ser Gly Ser Thr Asp Thr Gln Tyr Phe Gly Pro Gly
115 120 125
Thr Arg Leu Thr Val Leu
130
<210> 125
<211> 265
<212> PRT
<213> 智人(Homo sapiens)
<400> 125
Met Ala Gly Val Phe Leu Leu Tyr Val Ser Met Lys Met Gly Gly Thr
1 5 10 15
Thr Gly Gln Asn Ile Asp Gln Pro Thr Glu Met Thr Ala Thr Glu Gly
20 25 30
Ala Ile Val Gln Ile Asn Cys Thr Tyr Gln Thr Ser Gly Phe Asn Gly
35 40 45
Leu Phe Trp Tyr Gln Gln His Ala Gly Glu Ala Pro Thr Phe Leu Ser
50 55 60
Tyr Asn Val Leu Asp Gly Leu Glu Glu Lys Gly Arg Phe Ser Ser Phe
65 70 75 80
Leu Ser Arg Ser Lys Gly Tyr Ser Tyr Leu Leu Leu Lys Glu Leu Gln
85 90 95
Met Lys Asp Ser Ala Ser Tyr Leu Cys Ala Phe Tyr Tyr Gly Gly Ser
100 105 110
Gln Gly Asn Leu Ile Phe Gly Lys Gly Thr Lys Leu Ser Val Lys Pro
115 120 125
Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr Gln Leu Lys Asp Pro Arg
130 135 140
Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr Asp Phe Asp Ser Gln Ile
145 150 155 160
Asn Val Pro Lys Thr Met Glu Ser Gly Thr Phe Ile Thr Asp Lys Cys
165 170 175
Val Leu Asp Met Lys Ala Met Asp Ser Lys Ser Asn Gly Ala Ile Ala
180 185 190
Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln Asp Ile Phe Lys Glu Thr
195 200 205
Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro Cys Asp Ala Thr Leu Thr
210 215 220
Glu Lys Ser Phe Glu Thr Asp Met Asn Leu Asn Phe Gln Asn Leu Leu
225 230 235 240
Val Ile Val Leu Arg Ile Leu Leu Leu Lys Val Ala Gly Phe Asn Leu
245 250 255
Leu Met Thr Leu Arg Leu Trp Ser Ser
260 265
<210> 126
<211> 307
<212> PRT
<213> 智人(Homo sapiens)
<400> 126
Met His Thr Arg Leu Leu Cys Trp Val Val Leu Gly Phe Leu Gly Thr
1 5 10 15
Asp His Thr Gly Ala Gly Val Ser Gln Ser Pro Arg Tyr Lys Val Ala
20 25 30
Lys Arg Gly Gln Asp Val Ala Leu Arg Cys Asp Pro Ile Ser Gly His
35 40 45
Val Ser Leu Phe Trp Tyr Gln Gln Ala Leu Gly Gln Gly Pro Glu Phe
50 55 60
Leu Thr Tyr Phe Gln Asn Glu Ala Gln Leu Asp Lys Ser Gly Leu Pro
65 70 75 80
Ser Asp Arg Phe Phe Ala Glu Arg Pro Glu Gly Ser Val Ser Thr Leu
85 90 95
Lys Ile Gln Arg Thr Gln Gln Glu Asp Ser Ala Val Tyr Leu Cys Ala
100 105 110
Ser Ser Phe Gly Ser Gly Ser Thr Asp Thr Gln Tyr Phe Gly Pro Gly
115 120 125
Thr Arg Leu Thr Val Leu Glu Asp Leu Arg Asn Val Thr Pro Pro Lys
130 135 140
Val Ser Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys
145 150 155 160
Ala Thr Leu Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu
165 170 175
Leu Ser Trp Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr
180 185 190
Asp Pro Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser
195 200 205
Arg Leu Arg Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe
210 215 220
Arg Cys Gln Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro
225 230 235 240
Glu Gly Ser Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp
245 250 255
Gly Arg Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val
260 265 270
Leu Ser Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu
275 280 285
Tyr Ala Val Leu Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg
290 295 300
Lys Asn Ser
305
<210> 127
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 127
Thr Ser Gly Phe Asn Gly
1 5
<210> 128
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 128
Asn Val Leu Asp Gly Leu
1 5
<210> 129
<211> 14
<212> PRT
<213> 智人(Homo sapiens)
<400> 129
Cys Ala Val Tyr Pro Gly Gly Ser Gln Gly Asn Leu Ile Phe
1 5 10
<210> 130
<211> 5
<212> PRT
<213> 智人(Homo sapiens)
<400> 130
Ser Gly His Ala Thr
1 5
<210> 131
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 131
Phe Gln Asn Asn Gly Val
1 5
<210> 132
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 132
Cys Ala Ser Ser Leu Gly Thr Gly Ser Thr Asp Thr Gln Tyr Phe
1 5 10 15
<210> 133
<211> 128
<212> PRT
<213> 智人(Homo sapiens)
<400> 133
Met Ala Gly Val Phe Leu Leu Tyr Val Ser Met Lys Met Gly Gly Thr
1 5 10 15
Thr Gly Gln Asn Ile Asp Gln Pro Thr Glu Met Thr Ala Thr Glu Gly
20 25 30
Ala Ile Val Gln Ile Asn Cys Thr Tyr Gln Thr Ser Gly Phe Asn Gly
35 40 45
Leu Phe Trp Tyr Gln Gln His Ala Gly Glu Ala Pro Thr Phe Leu Ser
50 55 60
Tyr Asn Val Leu Asp Gly Leu Glu Glu Lys Gly Arg Phe Ser Ser Phe
65 70 75 80
Leu Ser Arg Ser Lys Gly Tyr Ser Tyr Leu Leu Leu Lys Glu Leu Gln
85 90 95
Met Lys Asp Ser Ala Ser Tyr Leu Cys Ala Val Tyr Pro Gly Gly Ser
100 105 110
Gln Gly Asn Leu Ile Phe Gly Lys Gly Thr Lys Leu Ser Val Lys Pro
115 120 125
<210> 134
<211> 134
<212> PRT
<213> 智人(Homo sapiens)
<400> 134
Met His Thr Arg Leu Leu Cys Trp Ala Ala Leu Cys Leu Leu Gly Ala
1 5 10 15
Glu Leu Thr Glu Ala Gly Val Ala Gln Ser Pro Arg Tyr Lys Ile Ile
20 25 30
Glu Lys Arg Gln Ser Val Ala Phe Trp Cys Asn Pro Ile Ser Gly His
35 40 45
Ala Thr Leu Tyr Trp Tyr Gln Gln Ile Leu Gly Gln Gly Pro Lys Leu
50 55 60
Leu Ile Gln Phe Gln Asn Asn Gly Val Val Asp Asp Ser Gln Leu Pro
65 70 75 80
Lys Asp Arg Phe Ser Ala Glu Arg Leu Lys Gly Val Asp Ser Thr Leu
85 90 95
Lys Ile Gln Pro Ala Lys Leu Glu Asp Ser Ala Val Tyr Leu Cys Ala
100 105 110
Ser Ser Leu Gly Thr Gly Ser Thr Asp Thr Gln Tyr Phe Gly Pro Gly
115 120 125
Thr Arg Leu Thr Val Leu
130
<210> 135
<211> 265
<212> PRT
<213> 智人(Homo sapiens)
<400> 135
Met Ala Gly Val Phe Leu Leu Tyr Val Ser Met Lys Met Gly Gly Thr
1 5 10 15
Thr Gly Gln Asn Ile Asp Gln Pro Thr Glu Met Thr Ala Thr Glu Gly
20 25 30
Ala Ile Val Gln Ile Asn Cys Thr Tyr Gln Thr Ser Gly Phe Asn Gly
35 40 45
Leu Phe Trp Tyr Gln Gln His Ala Gly Glu Ala Pro Thr Phe Leu Ser
50 55 60
Tyr Asn Val Leu Asp Gly Leu Glu Glu Lys Gly Arg Phe Ser Ser Phe
65 70 75 80
Leu Ser Arg Ser Lys Gly Tyr Ser Tyr Leu Leu Leu Lys Glu Leu Gln
85 90 95
Met Lys Asp Ser Ala Ser Tyr Leu Cys Ala Val Tyr Pro Gly Gly Ser
100 105 110
Gln Gly Asn Leu Ile Phe Gly Lys Gly Thr Lys Leu Ser Val Lys Pro
115 120 125
Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr Gln Leu Lys Asp Pro Arg
130 135 140
Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr Asp Phe Asp Ser Gln Ile
145 150 155 160
Asn Val Pro Lys Thr Met Glu Ser Gly Thr Phe Ile Thr Asp Lys Cys
165 170 175
Val Leu Asp Met Lys Ala Met Asp Ser Lys Ser Asn Gly Ala Ile Ala
180 185 190
Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln Asp Ile Phe Lys Glu Thr
195 200 205
Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro Cys Asp Ala Thr Leu Thr
210 215 220
Glu Lys Ser Phe Glu Thr Asp Met Asn Leu Asn Phe Gln Asn Leu Leu
225 230 235 240
Val Ile Val Leu Arg Ile Leu Leu Leu Lys Val Ala Gly Phe Asn Leu
245 250 255
Leu Met Thr Leu Arg Leu Trp Ser Ser
260 265
<210> 136
<211> 307
<212> PRT
<213> 智人(Homo sapiens)
<400> 136
Met His Thr Arg Leu Leu Cys Trp Ala Ala Leu Cys Leu Leu Gly Ala
1 5 10 15
Glu Leu Thr Glu Ala Gly Val Ala Gln Ser Pro Arg Tyr Lys Ile Ile
20 25 30
Glu Lys Arg Gln Ser Val Ala Phe Trp Cys Asn Pro Ile Ser Gly His
35 40 45
Ala Thr Leu Tyr Trp Tyr Gln Gln Ile Leu Gly Gln Gly Pro Lys Leu
50 55 60
Leu Ile Gln Phe Gln Asn Asn Gly Val Val Asp Asp Ser Gln Leu Pro
65 70 75 80
Lys Asp Arg Phe Ser Ala Glu Arg Leu Lys Gly Val Asp Ser Thr Leu
85 90 95
Lys Ile Gln Pro Ala Lys Leu Glu Asp Ser Ala Val Tyr Leu Cys Ala
100 105 110
Ser Ser Leu Gly Thr Gly Ser Thr Asp Thr Gln Tyr Phe Gly Pro Gly
115 120 125
Thr Arg Leu Thr Val Leu Glu Asp Leu Arg Asn Val Thr Pro Pro Lys
130 135 140
Val Ser Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys
145 150 155 160
Ala Thr Leu Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu
165 170 175
Leu Ser Trp Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr
180 185 190
Asp Pro Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser
195 200 205
Arg Leu Arg Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe
210 215 220
Arg Cys Gln Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro
225 230 235 240
Glu Gly Ser Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp
245 250 255
Gly Arg Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val
260 265 270
Leu Ser Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu
275 280 285
Tyr Ala Val Leu Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg
290 295 300
Lys Asn Ser
305
<210> 137
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 137
Asp Arg Gly Ser Gln Ser
1 5
<210> 138
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 138
Ile Tyr Ser Asn Gly Asp
1 5
<210> 139
<211> 11
<212> PRT
<213> 智人(Homo sapiens)
<400> 139
Cys Ala Val Ser Trp Tyr Ser Thr Leu Thr Phe
1 5 10
<210> 140
<211> 5
<212> PRT
<213> 智人(Homo sapiens)
<400> 140
Trp Ser His Ser Tyr
1 5
<210> 141
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 141
Ser Ala Ala Ala Asp Ile
1 5
<210> 142
<211> 13
<212> PRT
<213> 智人(Homo sapiens)
<400> 142
Cys Ala Ser Ser Gly Ser Arg Thr Asp Thr Gln Tyr Phe
1 5 10
<210> 143
<211> 130
<212> PRT
<213> 智人(Homo sapiens)
<400> 143
Met Ala Ser Leu Arg Val Leu Leu Val Ile Leu Trp Leu Gln Leu Ser
1 5 10 15
Trp Val Trp Ser Gln Gln Lys Glu Val Glu Gln Asn Ser Gly Pro Leu
20 25 30
Ser Val Pro Glu Gly Ala Ile Ala Ser Leu Asn Cys Thr Tyr Ser Asp
35 40 45
Arg Gly Ser Gln Ser Phe Phe Trp Tyr Arg Gln Tyr Ser Gly Lys Ser
50 55 60
Pro Glu Leu Ile Met Phe Ile Tyr Ser Asn Gly Asp Lys Glu Asp Gly
65 70 75 80
Arg Phe Thr Ala Gln Leu Asn Lys Ala Ser Gln Tyr Val Ser Leu Leu
85 90 95
Ile Arg Asp Ser Gln Pro Ser Asp Ser Ala Thr Tyr Leu Cys Ala Val
100 105 110
Ser Trp Tyr Ser Thr Leu Thr Phe Gly Lys Gly Thr Met Leu Leu Val
115 120 125
Ser Pro
130
<210> 144
<211> 131
<212> PRT
<213> 智人(Homo sapiens)
<400> 144
Met His Thr Arg Leu Phe Phe Tyr Val Ala Leu Cys Leu Leu Trp Ala
1 5 10 15
Gly His Arg Asp Ala Gly Ile Thr Gln Ser Pro Arg Tyr Lys Ile Thr
20 25 30
Glu Thr Gly Arg Gln Val Thr Leu Met Cys His Gln Thr Trp Ser His
35 40 45
Ser Tyr Met Phe Trp Tyr Arg Gln Asp Leu Gly His Gly Leu Arg Leu
50 55 60
Ile Tyr Tyr Ser Ala Ala Ala Asp Ile Thr Asp Lys Gly Glu Val Pro
65 70 75 80
Asp Gly Tyr Val Val Ser Arg Ser Lys Thr Glu Asn Phe Pro Leu Thr
85 90 95
Leu Glu Ser Ala Thr Arg Ser Gln Thr Ser Val Tyr Phe Cys Ala Ser
100 105 110
Ser Gly Ser Arg Thr Asp Thr Gln Tyr Phe Gly Pro Gly Thr Arg Leu
115 120 125
Thr Val Leu
130
<210> 145
<211> 267
<212> PRT
<213> 智人(Homo sapiens)
<400> 145
Met Ala Ser Leu Arg Val Leu Leu Val Ile Leu Trp Leu Gln Leu Ser
1 5 10 15
Trp Val Trp Ser Gln Gln Lys Glu Val Glu Gln Asn Ser Gly Pro Leu
20 25 30
Ser Val Pro Glu Gly Ala Ile Ala Ser Leu Asn Cys Thr Tyr Ser Asp
35 40 45
Arg Gly Ser Gln Ser Phe Phe Trp Tyr Arg Gln Tyr Ser Gly Lys Ser
50 55 60
Pro Glu Leu Ile Met Phe Ile Tyr Ser Asn Gly Asp Lys Glu Asp Gly
65 70 75 80
Arg Phe Thr Ala Gln Leu Asn Lys Ala Ser Gln Tyr Val Ser Leu Leu
85 90 95
Ile Arg Asp Ser Gln Pro Ser Asp Ser Ala Thr Tyr Leu Cys Ala Val
100 105 110
Ser Trp Tyr Ser Thr Leu Thr Phe Gly Lys Gly Thr Met Leu Leu Val
115 120 125
Ser Pro Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr Gln Leu Lys Asp
130 135 140
Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr Asp Phe Asp Ser
145 150 155 160
Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr Phe Ile Thr Asp
165 170 175
Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys Ser Asn Gly Ala
180 185 190
Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln Asp Ile Phe Lys
195 200 205
Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro Cys Asp Ala Thr
210 215 220
Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu Asn Phe Gln Asn
225 230 235 240
Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys Val Ala Gly Phe
245 250 255
Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser
260 265
<210> 146
<211> 304
<212> PRT
<213> 智人(Homo sapiens)
<400> 146
Met His Thr Arg Leu Phe Phe Tyr Val Ala Leu Cys Leu Leu Trp Ala
1 5 10 15
Gly His Arg Asp Ala Gly Ile Thr Gln Ser Pro Arg Tyr Lys Ile Thr
20 25 30
Glu Thr Gly Arg Gln Val Thr Leu Met Cys His Gln Thr Trp Ser His
35 40 45
Ser Tyr Met Phe Trp Tyr Arg Gln Asp Leu Gly His Gly Leu Arg Leu
50 55 60
Ile Tyr Tyr Ser Ala Ala Ala Asp Ile Thr Asp Lys Gly Glu Val Pro
65 70 75 80
Asp Gly Tyr Val Val Ser Arg Ser Lys Thr Glu Asn Phe Pro Leu Thr
85 90 95
Leu Glu Ser Ala Thr Arg Ser Gln Thr Ser Val Tyr Phe Cys Ala Ser
100 105 110
Ser Gly Ser Arg Thr Asp Thr Gln Tyr Phe Gly Pro Gly Thr Arg Leu
115 120 125
Thr Val Leu Glu Asp Leu Arg Asn Val Thr Pro Pro Lys Val Ser Leu
130 135 140
Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys Ala Thr Leu
145 150 155 160
Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu Leu Ser Trp
165 170 175
Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr Asp Pro Gln
180 185 190
Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser Arg Leu Arg
195 200 205
Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe Arg Cys Gln
210 215 220
Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro Glu Gly Ser
225 230 235 240
Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp Gly Arg Ala
245 250 255
Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val Leu Ser Ala
260 265 270
Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu Tyr Ala Val
275 280 285
Leu Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg Lys Asn Ser
290 295 300
<210> 147
<211> 5
<212> PRT
<213> 智人(Homo sapiens)
<400> 147
Ser Val Phe Ser Ser
1 5
<210> 148
<211> 7
<212> PRT
<213> 智人(Homo sapiens)
<400> 148
Val Val Thr Gly Gly Glu Val
1 5
<210> 149
<211> 12
<212> PRT
<213> 智人(Homo sapiens)
<400> 149
Cys Ala Gly Glu Phe Ala Gly Asn Gln Phe Tyr Phe
1 5 10
<210> 150
<211> 5
<212> PRT
<213> 智人(Homo sapiens)
<400> 150
Met Gly His Arg Ala
1 5
<210> 151
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 151
Tyr Ser Tyr Glu Lys Leu
1 5
<210> 152
<211> 14
<212> PRT
<213> 智人(Homo sapiens)
<400> 152
Cys Ala Ser Ser Gln Val Gly Leu Thr Tyr Glu Gln Tyr Phe
1 5 10
<210> 153
<211> 128
<212> PRT
<213> 智人(Homo sapiens)
<400> 153
Met Ala Leu Lys Phe Ser Val Ser Ile Leu Trp Ile Gln Leu Ala Trp
1 5 10 15
Val Ser Thr Gln Leu Leu Glu Gln Ser Pro Gln Phe Leu Ser Ile Gln
20 25 30
Glu Gly Glu Asn Leu Thr Val Tyr Cys Asn Ser Ser Ser Val Phe Ser
35 40 45
Ser Leu Gln Trp Tyr Arg Gln Glu Pro Gly Glu Gly Pro Val Leu Leu
50 55 60
Val Thr Val Val Thr Gly Gly Glu Val Lys Lys Leu Lys Arg Leu Thr
65 70 75 80
Phe Gln Phe Gly Asp Ala Arg Lys Asp Ser Ser Leu His Ile Thr Ala
85 90 95
Ala Gln Pro Gly Asp Thr Gly Leu Tyr Leu Cys Ala Gly Glu Phe Ala
100 105 110
Gly Asn Gln Phe Tyr Phe Gly Thr Gly Thr Ser Leu Thr Val Ile Pro
115 120 125
<210> 154
<211> 132
<212> PRT
<213> 智人(Homo sapiens)
<400> 154
Met His Cys Arg Leu Leu Cys Cys Ala Val Leu Cys Leu Leu Gly Ala
1 5 10 15
Val Pro Ile Asp Thr Glu Val Thr Gln Thr Pro Lys His Leu Val Met
20 25 30
Gly Met Thr Asn Lys Lys Ser Leu Lys Cys Glu Gln His Met Gly His
35 40 45
Arg Ala Met Tyr Trp Tyr Lys Gln Lys Ala Lys Lys Pro Pro Glu Leu
50 55 60
Met Phe Val Tyr Ser Tyr Glu Lys Leu Ser Ile Asn Glu Ser Val Pro
65 70 75 80
Ser Arg Phe Ser Pro Glu Cys Pro Asn Ser Ser Leu Leu Asn Leu His
85 90 95
Leu His Ala Leu Gln Pro Glu Asp Ser Ala Leu Tyr Leu Cys Ala Ser
100 105 110
Ser Gln Val Gly Leu Thr Tyr Glu Gln Tyr Phe Gly Pro Gly Thr Arg
115 120 125
Leu Thr Val Thr
130
<210> 155
<211> 265
<212> PRT
<213> 智人(Homo sapiens)
<400> 155
Met Ala Leu Lys Phe Ser Val Ser Ile Leu Trp Ile Gln Leu Ala Trp
1 5 10 15
Val Ser Thr Gln Leu Leu Glu Gln Ser Pro Gln Phe Leu Ser Ile Gln
20 25 30
Glu Gly Glu Asn Leu Thr Val Tyr Cys Asn Ser Ser Ser Val Phe Ser
35 40 45
Ser Leu Gln Trp Tyr Arg Gln Glu Pro Gly Glu Gly Pro Val Leu Leu
50 55 60
Val Thr Val Val Thr Gly Gly Glu Val Lys Lys Leu Lys Arg Leu Thr
65 70 75 80
Phe Gln Phe Gly Asp Ala Arg Lys Asp Ser Ser Leu His Ile Thr Ala
85 90 95
Ala Gln Pro Gly Asp Thr Gly Leu Tyr Leu Cys Ala Gly Glu Phe Ala
100 105 110
Gly Asn Gln Phe Tyr Phe Gly Thr Gly Thr Ser Leu Thr Val Ile Pro
115 120 125
Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr Gln Leu Lys Asp Pro Arg
130 135 140
Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr Asp Phe Asp Ser Gln Ile
145 150 155 160
Asn Val Pro Lys Thr Met Glu Ser Gly Thr Phe Ile Thr Asp Lys Cys
165 170 175
Val Leu Asp Met Lys Ala Met Asp Ser Lys Ser Asn Gly Ala Ile Ala
180 185 190
Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln Asp Ile Phe Lys Glu Thr
195 200 205
Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro Cys Asp Ala Thr Leu Thr
210 215 220
Glu Lys Ser Phe Glu Thr Asp Met Asn Leu Asn Phe Gln Asn Leu Leu
225 230 235 240
Val Ile Val Leu Arg Ile Leu Leu Leu Lys Val Ala Gly Phe Asn Leu
245 250 255
Leu Met Thr Leu Arg Leu Trp Ser Ser
260 265
<210> 156
<211> 305
<212> PRT
<213> 智人(Homo sapiens)
<400> 156
Met His Cys Arg Leu Leu Cys Cys Ala Val Leu Cys Leu Leu Gly Ala
1 5 10 15
Val Pro Ile Asp Thr Glu Val Thr Gln Thr Pro Lys His Leu Val Met
20 25 30
Gly Met Thr Asn Lys Lys Ser Leu Lys Cys Glu Gln His Met Gly His
35 40 45
Arg Ala Met Tyr Trp Tyr Lys Gln Lys Ala Lys Lys Pro Pro Glu Leu
50 55 60
Met Phe Val Tyr Ser Tyr Glu Lys Leu Ser Ile Asn Glu Ser Val Pro
65 70 75 80
Ser Arg Phe Ser Pro Glu Cys Pro Asn Ser Ser Leu Leu Asn Leu His
85 90 95
Leu His Ala Leu Gln Pro Glu Asp Ser Ala Leu Tyr Leu Cys Ala Ser
100 105 110
Ser Gln Val Gly Leu Thr Tyr Glu Gln Tyr Phe Gly Pro Gly Thr Arg
115 120 125
Leu Thr Val Thr Glu Asp Leu Arg Asn Val Thr Pro Pro Lys Val Ser
130 135 140
Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys Ala Thr
145 150 155 160
Leu Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu Leu Ser
165 170 175
Trp Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr Asp Pro
180 185 190
Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser Arg Leu
195 200 205
Arg Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe Arg Cys
210 215 220
Gln Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro Glu Gly
225 230 235 240
Ser Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp Gly Arg
245 250 255
Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val Leu Ser
260 265 270
Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu Tyr Ala
275 280 285
Val Leu Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg Lys Asn
290 295 300
Ser
305
<210> 157
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 157
Val Ser Gly Asn Pro Tyr
1 5
<210> 158
<211> 8
<212> PRT
<213> 智人(Homo sapiens)
<400> 158
Tyr Ile Thr Gly Asp Asn Leu Val
1 5
<210> 159
<211> 16
<212> PRT
<213> 智人(Homo sapiens)
<400> 159
Cys Ala Val Arg Asp Asn Ser Gly Gly Ser Asn Tyr Lys Leu Thr Phe
1 5 10 15
<210> 160
<211> 5
<212> PRT
<213> 智人(Homo sapiens)
<400> 160
Ser Gly His Ala Thr
1 5
<210> 161
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 161
Phe Gln Asn Asn Gly Val
1 5
<210> 162
<211> 13
<212> PRT
<213> 智人(Homo sapiens)
<400> 162
Cys Ala Ser Ser Leu Gly Gln Gly Gln Thr Gln Tyr Phe
1 5 10
<210> 163
<211> 135
<212> PRT
<213> 智人(Homo sapiens)
<400> 163
Met Ala Ser Ala Pro Ile Ser Met Leu Ala Met Leu Phe Thr Leu Ser
1 5 10 15
Gly Leu Arg Ala Gln Ser Val Ala Gln Pro Glu Asp Gln Val Asn Val
20 25 30
Ala Glu Gly Asn Pro Leu Thr Val Lys Cys Thr Tyr Ser Val Ser Gly
35 40 45
Asn Pro Tyr Leu Phe Trp Tyr Val Gln Tyr Pro Asn Arg Gly Leu Gln
50 55 60
Phe Leu Leu Lys Tyr Ile Thr Gly Asp Asn Leu Val Lys Gly Ser Tyr
65 70 75 80
Gly Phe Glu Ala Glu Phe Asn Lys Ser Gln Thr Ser Phe His Leu Lys
85 90 95
Lys Pro Ser Ala Leu Val Ser Asp Ser Ala Leu Tyr Phe Cys Ala Val
100 105 110
Arg Asp Asn Ser Gly Gly Ser Asn Tyr Lys Leu Thr Phe Gly Lys Gly
115 120 125
Thr Leu Leu Thr Val Asn Pro
130 135
<210> 164
<211> 132
<212> PRT
<213> 智人(Homo sapiens)
<400> 164
Met His Thr Arg Leu Leu Cys Trp Ala Ala Leu Cys Leu Leu Gly Ala
1 5 10 15
Glu Leu Thr Glu Ala Gly Val Ala Gln Ser Pro Arg Tyr Lys Ile Ile
20 25 30
Glu Lys Arg Gln Ser Val Ala Phe Trp Cys Asn Pro Ile Ser Gly His
35 40 45
Ala Thr Leu Tyr Trp Tyr Gln Gln Ile Leu Gly Gln Gly Pro Lys Leu
50 55 60
Leu Ile Gln Phe Gln Asn Asn Gly Val Val Asp Asp Ser Gln Leu Pro
65 70 75 80
Lys Asp Arg Phe Ser Ala Glu Arg Leu Lys Gly Val Asp Ser Thr Leu
85 90 95
Lys Ile Gln Pro Ala Lys Leu Glu Asp Ser Ala Val Tyr Leu Cys Ala
100 105 110
Ser Ser Leu Gly Gln Gly Gln Thr Gln Tyr Phe Gly Pro Gly Thr Arg
115 120 125
Leu Leu Val Leu
130
<210> 165
<211> 272
<212> PRT
<213> 智人(Homo sapiens)
<400> 165
Met Ala Ser Ala Pro Ile Ser Met Leu Ala Met Leu Phe Thr Leu Ser
1 5 10 15
Gly Leu Arg Ala Gln Ser Val Ala Gln Pro Glu Asp Gln Val Asn Val
20 25 30
Ala Glu Gly Asn Pro Leu Thr Val Lys Cys Thr Tyr Ser Val Ser Gly
35 40 45
Asn Pro Tyr Leu Phe Trp Tyr Val Gln Tyr Pro Asn Arg Gly Leu Gln
50 55 60
Phe Leu Leu Lys Tyr Ile Thr Gly Asp Asn Leu Val Lys Gly Ser Tyr
65 70 75 80
Gly Phe Glu Ala Glu Phe Asn Lys Ser Gln Thr Ser Phe His Leu Lys
85 90 95
Lys Pro Ser Ala Leu Val Ser Asp Ser Ala Leu Tyr Phe Cys Ala Val
100 105 110
Arg Asp Asn Ser Gly Gly Ser Asn Tyr Lys Leu Thr Phe Gly Lys Gly
115 120 125
Thr Leu Leu Thr Val Asn Pro Asn Ile Gln Asn Pro Glu Pro Ala Val
130 135 140
Tyr Gln Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe
145 150 155 160
Thr Asp Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly
165 170 175
Thr Phe Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser
180 185 190
Lys Ser Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys
195 200 205
Gln Asp Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val
210 215 220
Pro Cys Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn
225 230 235 240
Leu Asn Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu
245 250 255
Lys Val Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser
260 265 270
<210> 166
<211> 305
<212> PRT
<213> 智人(Homo sapiens)
<400> 166
Met His Thr Arg Leu Leu Cys Trp Ala Ala Leu Cys Leu Leu Gly Ala
1 5 10 15
Glu Leu Thr Glu Ala Gly Val Ala Gln Ser Pro Arg Tyr Lys Ile Ile
20 25 30
Glu Lys Arg Gln Ser Val Ala Phe Trp Cys Asn Pro Ile Ser Gly His
35 40 45
Ala Thr Leu Tyr Trp Tyr Gln Gln Ile Leu Gly Gln Gly Pro Lys Leu
50 55 60
Leu Ile Gln Phe Gln Asn Asn Gly Val Val Asp Asp Ser Gln Leu Pro
65 70 75 80
Lys Asp Arg Phe Ser Ala Glu Arg Leu Lys Gly Val Asp Ser Thr Leu
85 90 95
Lys Ile Gln Pro Ala Lys Leu Glu Asp Ser Ala Val Tyr Leu Cys Ala
100 105 110
Ser Ser Leu Gly Gln Gly Gln Thr Gln Tyr Phe Gly Pro Gly Thr Arg
115 120 125
Leu Leu Val Leu Glu Asp Leu Arg Asn Val Thr Pro Pro Lys Val Ser
130 135 140
Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys Ala Thr
145 150 155 160
Leu Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu Leu Ser
165 170 175
Trp Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr Asp Pro
180 185 190
Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser Arg Leu
195 200 205
Arg Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe Arg Cys
210 215 220
Gln Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro Glu Gly
225 230 235 240
Ser Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp Gly Arg
245 250 255
Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val Leu Ser
260 265 270
Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu Tyr Ala
275 280 285
Val Leu Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg Lys Asn
290 295 300
Ser
305
<210> 167
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 167
Ser Ser Val Ser Val Tyr
1 5
<210> 168
<211> 8
<212> PRT
<213> 智人(Homo sapiens)
<400> 168
Tyr Leu Ser Gly Ser Thr Leu Val
1 5
<210> 169
<211> 14
<212> PRT
<213> 智人(Homo sapiens)
<400> 169
Cys Ala Val Arg Gly Ser Ser Gly Thr Tyr Lys Tyr Ile Phe
1 5 10
<210> 170
<211> 5
<212> PRT
<213> 智人(Homo sapiens)
<400> 170
Met Asp His Glu Asn
1 5
<210> 171
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 171
Ser Tyr Asp Val Lys Met
1 5
<210> 172
<211> 13
<212> PRT
<213> 智人(Homo sapiens)
<400> 172
Cys Ala Ser Lys Gly Asp Gln Asn Thr Glu Ala Phe Phe
1 5 10
<210> 173
<211> 133
<212> PRT
<213> 智人(Homo sapiens)
<400> 173
Met Ala Leu Leu Leu Val Pro Ala Phe Gln Val Ile Phe Thr Leu Gly
1 5 10 15
Gly Thr Arg Ala Gln Ser Val Thr Gln Leu Asp Ser Gln Val Pro Val
20 25 30
Phe Glu Glu Ala Pro Val Glu Leu Arg Cys Asn Tyr Ser Ser Ser Val
35 40 45
Ser Val Tyr Leu Phe Trp Tyr Val Gln Tyr Pro Asn Gln Gly Leu Gln
50 55 60
Leu Leu Leu Lys Tyr Leu Ser Gly Ser Thr Leu Val Glu Ser Ile Asn
65 70 75 80
Gly Phe Glu Ala Glu Phe Asn Lys Ser Gln Thr Ser Phe His Leu Arg
85 90 95
Lys Pro Ser Val His Ile Ser Asp Thr Ala Glu Tyr Phe Cys Ala Val
100 105 110
Arg Gly Ser Ser Gly Thr Tyr Lys Tyr Ile Phe Gly Thr Gly Thr Arg
115 120 125
Leu Lys Val Leu Ala
130
<210> 174
<211> 131
<212> PRT
<213> 智人(Homo sapiens)
<400> 174
Met His Ile Arg Leu Leu Cys Arg Val Ala Phe Cys Phe Leu Ala Val
1 5 10 15
Gly Leu Val Asp Val Lys Val Thr Gln Ser Ser Arg Tyr Leu Val Lys
20 25 30
Arg Thr Gly Glu Lys Val Phe Leu Glu Cys Val Gln Asp Met Asp His
35 40 45
Glu Asn Met Phe Trp Tyr Arg Gln Asp Pro Gly Leu Gly Leu Arg Leu
50 55 60
Ile Tyr Phe Ser Tyr Asp Val Lys Met Lys Glu Lys Gly Asp Ile Pro
65 70 75 80
Glu Gly Tyr Ser Val Ser Arg Glu Lys Lys Glu Arg Phe Ser Leu Ile
85 90 95
Leu Glu Ser Ala Ser Thr Asn Gln Thr Ser Met Tyr Leu Cys Ala Ser
100 105 110
Lys Gly Asp Gln Asn Thr Glu Ala Phe Phe Gly Gln Gly Thr Arg Leu
115 120 125
Thr Val Val
130
<210> 175
<211> 270
<212> PRT
<213> 智人(Homo sapiens)
<400> 175
Met Ala Leu Leu Leu Val Pro Ala Phe Gln Val Ile Phe Thr Leu Gly
1 5 10 15
Gly Thr Arg Ala Gln Ser Val Thr Gln Leu Asp Ser Gln Val Pro Val
20 25 30
Phe Glu Glu Ala Pro Val Glu Leu Arg Cys Asn Tyr Ser Ser Ser Val
35 40 45
Ser Val Tyr Leu Phe Trp Tyr Val Gln Tyr Pro Asn Gln Gly Leu Gln
50 55 60
Leu Leu Leu Lys Tyr Leu Ser Gly Ser Thr Leu Val Glu Ser Ile Asn
65 70 75 80
Gly Phe Glu Ala Glu Phe Asn Lys Ser Gln Thr Ser Phe His Leu Arg
85 90 95
Lys Pro Ser Val His Ile Ser Asp Thr Ala Glu Tyr Phe Cys Ala Val
100 105 110
Arg Gly Ser Ser Gly Thr Tyr Lys Tyr Ile Phe Gly Thr Gly Thr Arg
115 120 125
Leu Lys Val Leu Ala Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr Gln
130 135 140
Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr Asp
145 150 155 160
Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr Phe
165 170 175
Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys Ser
180 185 190
Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln Asp
195 200 205
Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro Cys
210 215 220
Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu Asn
225 230 235 240
Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys Val
245 250 255
Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser
260 265 270
<210> 176
<211> 304
<212> PRT
<213> 智人(Homo sapiens)
<400> 176
Met His Ile Arg Leu Leu Cys Arg Val Ala Phe Cys Phe Leu Ala Val
1 5 10 15
Gly Leu Val Asp Val Lys Val Thr Gln Ser Ser Arg Tyr Leu Val Lys
20 25 30
Arg Thr Gly Glu Lys Val Phe Leu Glu Cys Val Gln Asp Met Asp His
35 40 45
Glu Asn Met Phe Trp Tyr Arg Gln Asp Pro Gly Leu Gly Leu Arg Leu
50 55 60
Ile Tyr Phe Ser Tyr Asp Val Lys Met Lys Glu Lys Gly Asp Ile Pro
65 70 75 80
Glu Gly Tyr Ser Val Ser Arg Glu Lys Lys Glu Arg Phe Ser Leu Ile
85 90 95
Leu Glu Ser Ala Ser Thr Asn Gln Thr Ser Met Tyr Leu Cys Ala Ser
100 105 110
Lys Gly Asp Gln Asn Thr Glu Ala Phe Phe Gly Gln Gly Thr Arg Leu
115 120 125
Thr Val Val Glu Asp Leu Arg Asn Val Thr Pro Pro Lys Val Ser Leu
130 135 140
Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys Ala Thr Leu
145 150 155 160
Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu Leu Ser Trp
165 170 175
Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr Asp Pro Gln
180 185 190
Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser Arg Leu Arg
195 200 205
Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe Arg Cys Gln
210 215 220
Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro Glu Gly Ser
225 230 235 240
Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp Gly Arg Ala
245 250 255
Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val Leu Ser Ala
260 265 270
Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu Tyr Ala Val
275 280 285
Leu Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg Lys Asn Ser
290 295 300
<210> 177
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 177
Thr Ser Gly Phe Asn Gly
1 5
<210> 178
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 178
Asn Val Leu Asp Gly Leu
1 5
<210> 179
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 179
Cys Ala Val Arg Asp Leu Gln Thr Gly Ala Asn Asn Leu Phe Phe
1 5 10 15
<210> 180
<211> 5
<212> PRT
<213> 智人(Homo sapiens)
<400> 180
Met Asp His Glu Asn
1 5
<210> 181
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 181
Ser Tyr Asp Val Lys Met
1 5
<210> 182
<211> 14
<212> PRT
<213> 智人(Homo sapiens)
<400> 182
Cys Ala Ser Ser Leu Thr Phe Gly Thr Thr Glu Ala Phe Phe
1 5 10
<210> 183
<211> 129
<212> PRT
<213> 智人(Homo sapiens)
<400> 183
Met Ala Gly Val Phe Leu Leu Tyr Val Ser Met Lys Met Gly Gly Thr
1 5 10 15
Thr Gly Gln Asn Ile Asp Gln Pro Thr Glu Met Thr Ala Thr Glu Gly
20 25 30
Ala Ile Val Gln Ile Asn Cys Thr Tyr Gln Thr Ser Gly Phe Asn Gly
35 40 45
Leu Phe Trp Tyr Gln Gln His Ala Gly Glu Ala Pro Thr Phe Leu Ser
50 55 60
Tyr Asn Val Leu Asp Gly Leu Glu Glu Lys Gly Arg Phe Ser Ser Phe
65 70 75 80
Leu Ser Arg Ser Lys Gly Tyr Ser Tyr Leu Leu Leu Lys Glu Leu Gln
85 90 95
Met Lys Asp Ser Ala Ser Tyr Leu Cys Ala Val Arg Asp Leu Gln Thr
100 105 110
Gly Ala Asn Asn Leu Phe Phe Gly Thr Gly Thr Arg Leu Thr Val Ile
115 120 125
Pro
<210> 184
<211> 132
<212> PRT
<213> 智人(Homo sapiens)
<400> 184
Met His Ile Arg Leu Leu Cys Arg Val Ala Phe Cys Phe Leu Ala Val
1 5 10 15
Gly Leu Val Asp Val Lys Val Thr Gln Ser Ser Arg Tyr Leu Val Lys
20 25 30
Arg Thr Gly Glu Lys Val Phe Leu Glu Cys Val Gln Asp Met Asp His
35 40 45
Glu Asn Met Phe Trp Tyr Arg Gln Asp Pro Gly Leu Gly Leu Arg Leu
50 55 60
Ile Tyr Phe Ser Tyr Asp Val Lys Met Lys Glu Lys Gly Asp Ile Pro
65 70 75 80
Glu Gly Tyr Ser Val Ser Arg Glu Lys Lys Glu Arg Phe Ser Leu Ile
85 90 95
Leu Glu Ser Ala Ser Thr Asn Gln Thr Ser Met Tyr Leu Cys Ala Ser
100 105 110
Ser Leu Thr Phe Gly Thr Thr Glu Ala Phe Phe Gly Gln Gly Thr Arg
115 120 125
Leu Thr Val Val
130
<210> 185
<211> 266
<212> PRT
<213> 智人(Homo sapiens)
<400> 185
Met Ala Gly Val Phe Leu Leu Tyr Val Ser Met Lys Met Gly Gly Thr
1 5 10 15
Thr Gly Gln Asn Ile Asp Gln Pro Thr Glu Met Thr Ala Thr Glu Gly
20 25 30
Ala Ile Val Gln Ile Asn Cys Thr Tyr Gln Thr Ser Gly Phe Asn Gly
35 40 45
Leu Phe Trp Tyr Gln Gln His Ala Gly Glu Ala Pro Thr Phe Leu Ser
50 55 60
Tyr Asn Val Leu Asp Gly Leu Glu Glu Lys Gly Arg Phe Ser Ser Phe
65 70 75 80
Leu Ser Arg Ser Lys Gly Tyr Ser Tyr Leu Leu Leu Lys Glu Leu Gln
85 90 95
Met Lys Asp Ser Ala Ser Tyr Leu Cys Ala Val Arg Asp Leu Gln Thr
100 105 110
Gly Ala Asn Asn Leu Phe Phe Gly Thr Gly Thr Arg Leu Thr Val Ile
115 120 125
Pro Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr Gln Leu Lys Asp Pro
130 135 140
Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr Asp Phe Asp Ser Gln
145 150 155 160
Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr Phe Ile Thr Asp Lys
165 170 175
Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys Ser Asn Gly Ala Ile
180 185 190
Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln Asp Ile Phe Lys Glu
195 200 205
Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro Cys Asp Ala Thr Leu
210 215 220
Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu Asn Phe Gln Asn Leu
225 230 235 240
Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys Val Ala Gly Phe Asn
245 250 255
Leu Leu Met Thr Leu Arg Leu Trp Ser Ser
260 265
<210> 186
<211> 305
<212> PRT
<213> 智人(Homo sapiens)
<400> 186
Met His Ile Arg Leu Leu Cys Arg Val Ala Phe Cys Phe Leu Ala Val
1 5 10 15
Gly Leu Val Asp Val Lys Val Thr Gln Ser Ser Arg Tyr Leu Val Lys
20 25 30
Arg Thr Gly Glu Lys Val Phe Leu Glu Cys Val Gln Asp Met Asp His
35 40 45
Glu Asn Met Phe Trp Tyr Arg Gln Asp Pro Gly Leu Gly Leu Arg Leu
50 55 60
Ile Tyr Phe Ser Tyr Asp Val Lys Met Lys Glu Lys Gly Asp Ile Pro
65 70 75 80
Glu Gly Tyr Ser Val Ser Arg Glu Lys Lys Glu Arg Phe Ser Leu Ile
85 90 95
Leu Glu Ser Ala Ser Thr Asn Gln Thr Ser Met Tyr Leu Cys Ala Ser
100 105 110
Ser Leu Thr Phe Gly Thr Thr Glu Ala Phe Phe Gly Gln Gly Thr Arg
115 120 125
Leu Thr Val Val Glu Asp Leu Arg Asn Val Thr Pro Pro Lys Val Ser
130 135 140
Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys Ala Thr
145 150 155 160
Leu Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu Leu Ser
165 170 175
Trp Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr Asp Pro
180 185 190
Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser Arg Leu
195 200 205
Arg Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe Arg Cys
210 215 220
Gln Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro Glu Gly
225 230 235 240
Ser Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp Gly Arg
245 250 255
Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val Leu Ser
260 265 270
Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu Tyr Ala
275 280 285
Val Leu Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg Lys Asn
290 295 300
Ser
305
<210> 187
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 187
Val Thr Asn Phe Arg Ser
1 5
<210> 188
<211> 7
<212> PRT
<213> 智人(Homo sapiens)
<400> 188
Leu Thr Ser Ser Gly Ile Glu
1 5
<210> 189
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 189
Cys Ala Gly Gln Asn Tyr Gly Gly Ser Gln Gly Asn Leu Ile Phe
1 5 10 15
<210> 190
<211> 5
<212> PRT
<213> 智人(Homo sapiens)
<400> 190
Ser Asn His Leu Tyr
1 5
<210> 191
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 191
Phe Tyr Asn Asn Glu Ile
1 5
<210> 192
<211> 12
<212> PRT
<213> 智人(Homo sapiens)
<400> 192
Cys Ala Ser Arg Asp Pro Ala Tyr Glu Gln Tyr Phe
1 5 10
<210> 193
<211> 134
<212> PRT
<213> 智人(Homo sapiens)
<400> 193
Met Ala Lys Cys Pro Gln Ala Leu Leu Ala Ile Phe Trp Leu Leu Leu
1 5 10 15
Ser Trp Val Ser Ser Glu Asp Lys Val Val Gln Ser Pro Leu Ser Leu
20 25 30
Val Val His Glu Gly Asp Thr Val Thr Leu Asn Cys Ser Tyr Glu Val
35 40 45
Thr Asn Phe Arg Ser Leu Leu Trp Tyr Lys Gln Glu Lys Lys Ala Pro
50 55 60
Thr Phe Leu Phe Met Leu Thr Ser Ser Gly Ile Glu Lys Lys Ser Gly
65 70 75 80
Arg Leu Ser Ser Ile Leu Asp Lys Lys Glu Leu Ser Ser Ile Leu Asn
85 90 95
Ile Thr Ala Thr Gln Thr Gly Asp Ser Ala Ile Tyr Leu Cys Ala Gly
100 105 110
Gln Asn Tyr Gly Gly Ser Gln Gly Asn Leu Ile Phe Gly Lys Gly Thr
115 120 125
Lys Leu Ser Val Lys Pro
130
<210> 194
<211> 131
<212> PRT
<213> 智人(Homo sapiens)
<400> 194
Met His Thr Trp Leu Val Cys Trp Ala Ile Phe Ser Leu Leu Lys Ala
1 5 10 15
Gly Leu Thr Glu Pro Glu Val Thr Gln Thr Pro Ser His Gln Val Thr
20 25 30
Gln Met Gly Gln Glu Val Ile Leu Arg Cys Val Pro Ile Ser Asn His
35 40 45
Leu Tyr Phe Tyr Trp Tyr Arg Gln Ile Leu Gly Gln Lys Val Glu Phe
50 55 60
Leu Val Ser Phe Tyr Asn Asn Glu Ile Ser Glu Lys Ser Glu Ile Phe
65 70 75 80
Asp Asp Gln Phe Ser Val Glu Arg Pro Asp Gly Ser Asn Phe Thr Leu
85 90 95
Lys Ile Arg Ser Thr Lys Leu Glu Asp Ser Ala Met Tyr Phe Cys Ala
100 105 110
Ser Arg Asp Pro Ala Tyr Glu Gln Tyr Phe Gly Pro Gly Thr Arg Leu
115 120 125
Thr Val Thr
130
<210> 195
<211> 271
<212> PRT
<213> 智人(Homo sapiens)
<400> 195
Met Ala Lys Cys Pro Gln Ala Leu Leu Ala Ile Phe Trp Leu Leu Leu
1 5 10 15
Ser Trp Val Ser Ser Glu Asp Lys Val Val Gln Ser Pro Leu Ser Leu
20 25 30
Val Val His Glu Gly Asp Thr Val Thr Leu Asn Cys Ser Tyr Glu Val
35 40 45
Thr Asn Phe Arg Ser Leu Leu Trp Tyr Lys Gln Glu Lys Lys Ala Pro
50 55 60
Thr Phe Leu Phe Met Leu Thr Ser Ser Gly Ile Glu Lys Lys Ser Gly
65 70 75 80
Arg Leu Ser Ser Ile Leu Asp Lys Lys Glu Leu Ser Ser Ile Leu Asn
85 90 95
Ile Thr Ala Thr Gln Thr Gly Asp Ser Ala Ile Tyr Leu Cys Ala Gly
100 105 110
Gln Asn Tyr Gly Gly Ser Gln Gly Asn Leu Ile Phe Gly Lys Gly Thr
115 120 125
Lys Leu Ser Val Lys Pro Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr
130 135 140
Gln Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr
145 150 155 160
Asp Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr
165 170 175
Phe Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys
180 185 190
Ser Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln
195 200 205
Asp Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro
210 215 220
Cys Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu
225 230 235 240
Asn Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys
245 250 255
Val Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser
260 265 270
<210> 196
<211> 304
<212> PRT
<213> 智人(Homo sapiens)
<400> 196
Met His Thr Trp Leu Val Cys Trp Ala Ile Phe Ser Leu Leu Lys Ala
1 5 10 15
Gly Leu Thr Glu Pro Glu Val Thr Gln Thr Pro Ser His Gln Val Thr
20 25 30
Gln Met Gly Gln Glu Val Ile Leu Arg Cys Val Pro Ile Ser Asn His
35 40 45
Leu Tyr Phe Tyr Trp Tyr Arg Gln Ile Leu Gly Gln Lys Val Glu Phe
50 55 60
Leu Val Ser Phe Tyr Asn Asn Glu Ile Ser Glu Lys Ser Glu Ile Phe
65 70 75 80
Asp Asp Gln Phe Ser Val Glu Arg Pro Asp Gly Ser Asn Phe Thr Leu
85 90 95
Lys Ile Arg Ser Thr Lys Leu Glu Asp Ser Ala Met Tyr Phe Cys Ala
100 105 110
Ser Arg Asp Pro Ala Tyr Glu Gln Tyr Phe Gly Pro Gly Thr Arg Leu
115 120 125
Thr Val Thr Glu Asp Leu Arg Asn Val Thr Pro Pro Lys Val Ser Leu
130 135 140
Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys Ala Thr Leu
145 150 155 160
Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu Leu Ser Trp
165 170 175
Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr Asp Pro Gln
180 185 190
Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser Arg Leu Arg
195 200 205
Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe Arg Cys Gln
210 215 220
Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro Glu Gly Ser
225 230 235 240
Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp Gly Arg Ala
245 250 255
Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val Leu Ser Ala
260 265 270
Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu Tyr Ala Val
275 280 285
Leu Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg Lys Asn Ser
290 295 300
<210> 197
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 197
Asp Arg Gly Ser Gln Ser
1 5
<210> 198
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 198
Ile Tyr Ser Asn Gly Asp
1 5
<210> 199
<211> 16
<212> PRT
<213> 智人(Homo sapiens)
<400> 199
Cys Ala Val Asn Pro Pro Val Lys Thr Ser Tyr Asp Lys Val Ile Phe
1 5 10 15
<210> 200
<211> 5
<212> PRT
<213> 智人(Homo sapiens)
<400> 200
Ser Gly His Val Ser
1 5
<210> 201
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 201
Phe Asn Tyr Glu Ala Gln
1 5
<210> 202
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 202
Cys Ala Ser Ser His Arg Glu Pro His Thr Gly Glu Leu Phe Phe
1 5 10 15
<210> 203
<211> 135
<212> PRT
<213> 智人(Homo sapiens)
<400> 203
Met Ala Ser Leu Arg Val Leu Leu Val Ile Leu Trp Leu Gln Leu Ser
1 5 10 15
Trp Val Trp Ser Gln Gln Lys Glu Val Glu Gln Asn Ser Gly Pro Leu
20 25 30
Ser Val Pro Glu Gly Ala Ile Ala Ser Leu Asn Cys Thr Tyr Ser Asp
35 40 45
Arg Gly Ser Gln Ser Phe Phe Trp Tyr Arg Gln Tyr Ser Gly Lys Ser
50 55 60
Pro Glu Leu Ile Met Phe Ile Tyr Ser Asn Gly Asp Lys Glu Asp Gly
65 70 75 80
Arg Phe Thr Ala Gln Leu Asn Lys Ala Ser Gln Tyr Val Ser Leu Leu
85 90 95
Ile Arg Asp Ser Gln Pro Ser Asp Ser Ala Thr Tyr Leu Cys Ala Val
100 105 110
Asn Pro Pro Val Lys Thr Ser Tyr Asp Lys Val Ile Phe Gly Pro Gly
115 120 125
Thr Ser Leu Ser Val Ile Pro
130 135
<210> 204
<211> 134
<212> PRT
<213> 智人(Homo sapiens)
<400> 204
Met His Thr Ser Leu Leu Cys Trp Val Val Leu Gly Phe Leu Gly Thr
1 5 10 15
Asp His Thr Gly Ala Gly Val Ser Gln Ser Pro Arg Tyr Lys Val Thr
20 25 30
Lys Arg Gly Gln Asp Val Ala Leu Arg Cys Asp Pro Ile Ser Gly His
35 40 45
Val Ser Leu Tyr Trp Tyr Arg Gln Ala Leu Gly Gln Gly Pro Glu Phe
50 55 60
Leu Thr Tyr Phe Asn Tyr Glu Ala Gln Gln Asp Lys Ser Gly Leu Pro
65 70 75 80
Asn Asp Arg Phe Ser Ala Glu Arg Pro Glu Gly Ser Ile Ser Thr Leu
85 90 95
Thr Ile Gln Arg Thr Glu Gln Arg Asp Ser Ala Met Tyr Arg Cys Ala
100 105 110
Ser Ser His Arg Glu Pro His Thr Gly Glu Leu Phe Phe Gly Glu Gly
115 120 125
Ser Arg Leu Thr Val Leu
130
<210> 205
<211> 272
<212> PRT
<213> 智人(Homo sapiens)
<400> 205
Met Ala Ser Leu Arg Val Leu Leu Val Ile Leu Trp Leu Gln Leu Ser
1 5 10 15
Trp Val Trp Ser Gln Gln Lys Glu Val Glu Gln Asn Ser Gly Pro Leu
20 25 30
Ser Val Pro Glu Gly Ala Ile Ala Ser Leu Asn Cys Thr Tyr Ser Asp
35 40 45
Arg Gly Ser Gln Ser Phe Phe Trp Tyr Arg Gln Tyr Ser Gly Lys Ser
50 55 60
Pro Glu Leu Ile Met Phe Ile Tyr Ser Asn Gly Asp Lys Glu Asp Gly
65 70 75 80
Arg Phe Thr Ala Gln Leu Asn Lys Ala Ser Gln Tyr Val Ser Leu Leu
85 90 95
Ile Arg Asp Ser Gln Pro Ser Asp Ser Ala Thr Tyr Leu Cys Ala Val
100 105 110
Asn Pro Pro Val Lys Thr Ser Tyr Asp Lys Val Ile Phe Gly Pro Gly
115 120 125
Thr Ser Leu Ser Val Ile Pro Asn Ile Gln Asn Pro Glu Pro Ala Val
130 135 140
Tyr Gln Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe
145 150 155 160
Thr Asp Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly
165 170 175
Thr Phe Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser
180 185 190
Lys Ser Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys
195 200 205
Gln Asp Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val
210 215 220
Pro Cys Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn
225 230 235 240
Leu Asn Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu
245 250 255
Lys Val Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser
260 265 270
<210> 206
<211> 307
<212> PRT
<213> 智人(Homo sapiens)
<400> 206
Met His Thr Ser Leu Leu Cys Trp Val Val Leu Gly Phe Leu Gly Thr
1 5 10 15
Asp His Thr Gly Ala Gly Val Ser Gln Ser Pro Arg Tyr Lys Val Thr
20 25 30
Lys Arg Gly Gln Asp Val Ala Leu Arg Cys Asp Pro Ile Ser Gly His
35 40 45
Val Ser Leu Tyr Trp Tyr Arg Gln Ala Leu Gly Gln Gly Pro Glu Phe
50 55 60
Leu Thr Tyr Phe Asn Tyr Glu Ala Gln Gln Asp Lys Ser Gly Leu Pro
65 70 75 80
Asn Asp Arg Phe Ser Ala Glu Arg Pro Glu Gly Ser Ile Ser Thr Leu
85 90 95
Thr Ile Gln Arg Thr Glu Gln Arg Asp Ser Ala Met Tyr Arg Cys Ala
100 105 110
Ser Ser His Arg Glu Pro His Thr Gly Glu Leu Phe Phe Gly Glu Gly
115 120 125
Ser Arg Leu Thr Val Leu Glu Asp Leu Arg Asn Val Thr Pro Pro Lys
130 135 140
Val Ser Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys
145 150 155 160
Ala Thr Leu Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu
165 170 175
Leu Ser Trp Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr
180 185 190
Asp Pro Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser
195 200 205
Arg Leu Arg Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe
210 215 220
Arg Cys Gln Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro
225 230 235 240
Glu Gly Ser Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp
245 250 255
Gly Arg Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val
260 265 270
Leu Ser Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu
275 280 285
Tyr Ala Val Leu Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg
290 295 300
Lys Asn Ser
305
<210> 207
<211> 7
<212> PRT
<213> 智人(Homo sapiens)
<400> 207
Thr Arg Asp Thr Thr Tyr Tyr
1 5
<210> 208
<211> 8
<212> PRT
<213> 智人(Homo sapiens)
<400> 208
Arg Asn Ser Phe Asp Glu Gln Asn
1 5
<210> 209
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 209
Cys Ala Leu Ser Glu Val Asp Ser Gly Asn Thr Pro Leu Val Phe
1 5 10 15
<210> 210
<211> 5
<212> PRT
<213> 智人(Homo sapiens)
<400> 210
Ser Gly Asp Leu Ser
1 5
<210> 211
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 211
Tyr Tyr Asn Gly Glu Glu
1 5
<210> 212
<211> 16
<212> PRT
<213> 智人(Homo sapiens)
<400> 212
Cys Ala Ser Ser Val Gly Ser Ser Ser Ser Thr Asp Thr Gln Tyr Phe
1 5 10 15
<210> 213
<211> 136
<212> PRT
<213> 智人(Homo sapiens)
<400> 213
Met Ala Thr Ala Ser Leu Leu Arg Ala Val Ile Ala Ser Ile Cys Val
1 5 10 15
Val Ser Ser Met Ala Gln Lys Val Thr Gln Ala Gln Thr Glu Ile Ser
20 25 30
Val Val Glu Lys Glu Asp Val Thr Leu Asp Cys Val Tyr Glu Thr Arg
35 40 45
Asp Thr Thr Tyr Tyr Leu Phe Trp Tyr Lys Gln Pro Pro Ser Gly Glu
50 55 60
Leu Val Phe Leu Ile Arg Arg Asn Ser Phe Asp Glu Gln Asn Glu Ile
65 70 75 80
Ser Gly Arg Tyr Ser Trp Asn Phe Gln Lys Ser Thr Ser Ser Phe Asn
85 90 95
Phe Thr Ile Thr Ala Ser Gln Val Val Asp Ser Ala Val Tyr Phe Cys
100 105 110
Ala Leu Ser Glu Val Asp Ser Gly Asn Thr Pro Leu Val Phe Gly Lys
115 120 125
Gly Thr Arg Leu Ser Val Ile Ala
130 135
<210> 214
<211> 134
<212> PRT
<213> 智人(Homo sapiens)
<400> 214
Met His Phe Arg Leu Leu Cys Cys Val Ala Phe Cys Leu Leu Gly Ala
1 5 10 15
Gly Pro Val Asp Ser Gly Val Thr Gln Thr Pro Lys His Leu Ile Thr
20 25 30
Ala Thr Gly Gln Arg Val Thr Leu Arg Cys Ser Pro Arg Ser Gly Asp
35 40 45
Leu Ser Val Tyr Trp Tyr Gln Gln Ser Leu Asp Gln Gly Leu Gln Phe
50 55 60
Leu Ile Gln Tyr Tyr Asn Gly Glu Glu Arg Ala Lys Gly Asn Ile Leu
65 70 75 80
Glu Arg Phe Ser Ala Gln Gln Phe Pro Asp Leu His Ser Glu Leu Asn
85 90 95
Leu Ser Ser Leu Glu Leu Gly Asp Ser Ala Leu Tyr Phe Cys Ala Ser
100 105 110
Ser Val Gly Ser Ser Ser Ser Thr Asp Thr Gln Tyr Phe Gly Pro Gly
115 120 125
Thr Arg Leu Thr Val Leu
130
<210> 215
<211> 273
<212> PRT
<213> 智人(Homo sapiens)
<400> 215
Met Ala Thr Ala Ser Leu Leu Arg Ala Val Ile Ala Ser Ile Cys Val
1 5 10 15
Val Ser Ser Met Ala Gln Lys Val Thr Gln Ala Gln Thr Glu Ile Ser
20 25 30
Val Val Glu Lys Glu Asp Val Thr Leu Asp Cys Val Tyr Glu Thr Arg
35 40 45
Asp Thr Thr Tyr Tyr Leu Phe Trp Tyr Lys Gln Pro Pro Ser Gly Glu
50 55 60
Leu Val Phe Leu Ile Arg Arg Asn Ser Phe Asp Glu Gln Asn Glu Ile
65 70 75 80
Ser Gly Arg Tyr Ser Trp Asn Phe Gln Lys Ser Thr Ser Ser Phe Asn
85 90 95
Phe Thr Ile Thr Ala Ser Gln Val Val Asp Ser Ala Val Tyr Phe Cys
100 105 110
Ala Leu Ser Glu Val Asp Ser Gly Asn Thr Pro Leu Val Phe Gly Lys
115 120 125
Gly Thr Arg Leu Ser Val Ile Ala Asn Ile Gln Asn Pro Glu Pro Ala
130 135 140
Val Tyr Gln Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu
145 150 155 160
Phe Thr Asp Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser
165 170 175
Gly Thr Phe Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp
180 185 190
Ser Lys Ser Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr
195 200 205
Cys Gln Asp Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp
210 215 220
Val Pro Cys Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met
225 230 235 240
Asn Leu Asn Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu
245 250 255
Leu Lys Val Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser
260 265 270
Ser
<210> 216
<211> 307
<212> PRT
<213> 智人(Homo sapiens)
<400> 216
Met His Phe Arg Leu Leu Cys Cys Val Ala Phe Cys Leu Leu Gly Ala
1 5 10 15
Gly Pro Val Asp Ser Gly Val Thr Gln Thr Pro Lys His Leu Ile Thr
20 25 30
Ala Thr Gly Gln Arg Val Thr Leu Arg Cys Ser Pro Arg Ser Gly Asp
35 40 45
Leu Ser Val Tyr Trp Tyr Gln Gln Ser Leu Asp Gln Gly Leu Gln Phe
50 55 60
Leu Ile Gln Tyr Tyr Asn Gly Glu Glu Arg Ala Lys Gly Asn Ile Leu
65 70 75 80
Glu Arg Phe Ser Ala Gln Gln Phe Pro Asp Leu His Ser Glu Leu Asn
85 90 95
Leu Ser Ser Leu Glu Leu Gly Asp Ser Ala Leu Tyr Phe Cys Ala Ser
100 105 110
Ser Val Gly Ser Ser Ser Ser Thr Asp Thr Gln Tyr Phe Gly Pro Gly
115 120 125
Thr Arg Leu Thr Val Leu Glu Asp Leu Arg Asn Val Thr Pro Pro Lys
130 135 140
Val Ser Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys
145 150 155 160
Ala Thr Leu Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu
165 170 175
Leu Ser Trp Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr
180 185 190
Asp Pro Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser
195 200 205
Arg Leu Arg Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe
210 215 220
Arg Cys Gln Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro
225 230 235 240
Glu Gly Ser Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp
245 250 255
Gly Arg Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val
260 265 270
Leu Ser Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu
275 280 285
Tyr Ala Val Leu Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg
290 295 300
Lys Asn Ser
305
<210> 217
<211> 7
<212> PRT
<213> 智人(Homo sapiens)
<400> 217
Thr Arg Asp Thr Thr Tyr Tyr
1 5
<210> 218
<211> 8
<212> PRT
<213> 智人(Homo sapiens)
<400> 218
Arg Asn Ser Phe Asp Glu Gln Asn
1 5
<210> 219
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 219
Cys Ala Leu Ser Glu Val Asp Ser Gly Asn Thr Pro Leu Val Phe
1 5 10 15
<210> 220
<211> 5
<212> PRT
<213> 智人(Homo sapiens)
<400> 220
Ser Gly Asp Leu Ser
1 5
<210> 221
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 221
Tyr Tyr Asn Gly Glu Glu
1 5
<210> 222
<211> 16
<212> PRT
<213> 智人(Homo sapiens)
<400> 222
Cys Ala Ser Ser Val Gly Ser Ser Ser Ser Thr Asp Thr Gln Tyr Phe
1 5 10 15
<210> 223
<211> 136
<212> PRT
<213> 智人(Homo sapiens)
<400> 223
Met Ala Thr Ala Ser Leu Leu Arg Ala Val Ile Ala Ser Ile Cys Val
1 5 10 15
Val Ser Ser Met Ala Gln Lys Val Thr Gln Ala Gln Thr Glu Ile Ser
20 25 30
Val Val Glu Lys Glu Asp Val Thr Leu Asp Cys Val Tyr Glu Thr Arg
35 40 45
Asp Thr Thr Tyr Tyr Leu Phe Trp Tyr Lys Gln Pro Pro Ser Gly Glu
50 55 60
Leu Val Phe Leu Ile Arg Arg Asn Ser Phe Asp Glu Gln Asn Glu Ile
65 70 75 80
Ser Gly Arg Tyr Ser Trp Asn Phe Gln Lys Ser Thr Ser Ser Phe Asn
85 90 95
Phe Thr Ile Thr Ala Ser Gln Val Val Asp Ser Ala Val Tyr Phe Cys
100 105 110
Ala Leu Ser Glu Val Asp Ser Gly Asn Thr Pro Leu Val Phe Gly Lys
115 120 125
Gly Thr Arg Leu Ser Val Ile Ala
130 135
<210> 224
<211> 134
<212> PRT
<213> 智人(Homo sapiens)
<400> 224
Met His Phe Arg Leu Leu Cys Cys Val Ala Phe Cys Leu Leu Gly Ala
1 5 10 15
Gly Pro Val Asp Ser Gly Val Thr Gln Thr Pro Lys His Leu Ile Thr
20 25 30
Ala Thr Gly Gln Arg Val Thr Leu Arg Cys Ser Pro Arg Ser Gly Asp
35 40 45
Leu Ser Val Tyr Trp Tyr Gln Gln Ser Leu Asp Gln Gly Leu Gln Phe
50 55 60
Leu Ile His Tyr Tyr Asn Gly Glu Glu Arg Ala Lys Gly Asn Ile Leu
65 70 75 80
Glu Arg Phe Ser Ala Gln Gln Phe Pro Asp Leu His Ser Glu Leu Asn
85 90 95
Leu Ser Ser Leu Glu Leu Gly Asp Ser Ala Leu Tyr Phe Cys Ala Ser
100 105 110
Ser Val Gly Ser Ser Ser Ser Thr Asp Thr Gln Tyr Phe Gly Pro Gly
115 120 125
Thr Arg Leu Thr Val Leu
130
<210> 225
<211> 273
<212> PRT
<213> 智人(Homo sapiens)
<400> 225
Met Ala Thr Ala Ser Leu Leu Arg Ala Val Ile Ala Ser Ile Cys Val
1 5 10 15
Val Ser Ser Met Ala Gln Lys Val Thr Gln Ala Gln Thr Glu Ile Ser
20 25 30
Val Val Glu Lys Glu Asp Val Thr Leu Asp Cys Val Tyr Glu Thr Arg
35 40 45
Asp Thr Thr Tyr Tyr Leu Phe Trp Tyr Lys Gln Pro Pro Ser Gly Glu
50 55 60
Leu Val Phe Leu Ile Arg Arg Asn Ser Phe Asp Glu Gln Asn Glu Ile
65 70 75 80
Ser Gly Arg Tyr Ser Trp Asn Phe Gln Lys Ser Thr Ser Ser Phe Asn
85 90 95
Phe Thr Ile Thr Ala Ser Gln Val Val Asp Ser Ala Val Tyr Phe Cys
100 105 110
Ala Leu Ser Glu Val Asp Ser Gly Asn Thr Pro Leu Val Phe Gly Lys
115 120 125
Gly Thr Arg Leu Ser Val Ile Ala Asn Ile Gln Asn Pro Glu Pro Ala
130 135 140
Val Tyr Gln Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu
145 150 155 160
Phe Thr Asp Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser
165 170 175
Gly Thr Phe Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp
180 185 190
Ser Lys Ser Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr
195 200 205
Cys Gln Asp Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp
210 215 220
Val Pro Cys Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met
225 230 235 240
Asn Leu Asn Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu
245 250 255
Leu Lys Val Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser
260 265 270
Ser
<210> 226
<211> 307
<212> PRT
<213> 智人(Homo sapiens)
<400> 226
Met His Phe Arg Leu Leu Cys Cys Val Ala Phe Cys Leu Leu Gly Ala
1 5 10 15
Gly Pro Val Asp Ser Gly Val Thr Gln Thr Pro Lys His Leu Ile Thr
20 25 30
Ala Thr Gly Gln Arg Val Thr Leu Arg Cys Ser Pro Arg Ser Gly Asp
35 40 45
Leu Ser Val Tyr Trp Tyr Gln Gln Ser Leu Asp Gln Gly Leu Gln Phe
50 55 60
Leu Ile His Tyr Tyr Asn Gly Glu Glu Arg Ala Lys Gly Asn Ile Leu
65 70 75 80
Glu Arg Phe Ser Ala Gln Gln Phe Pro Asp Leu His Ser Glu Leu Asn
85 90 95
Leu Ser Ser Leu Glu Leu Gly Asp Ser Ala Leu Tyr Phe Cys Ala Ser
100 105 110
Ser Val Gly Ser Ser Ser Ser Thr Asp Thr Gln Tyr Phe Gly Pro Gly
115 120 125
Thr Arg Leu Thr Val Leu Glu Asp Leu Arg Asn Val Thr Pro Pro Lys
130 135 140
Val Ser Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys
145 150 155 160
Ala Thr Leu Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu
165 170 175
Leu Ser Trp Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr
180 185 190
Asp Pro Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser
195 200 205
Arg Leu Arg Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe
210 215 220
Arg Cys Gln Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro
225 230 235 240
Glu Gly Ser Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp
245 250 255
Gly Arg Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val
260 265 270
Leu Ser Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu
275 280 285
Tyr Ala Val Leu Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg
290 295 300
Lys Asn Ser
305
<210> 227
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 227
Asn Ser Ala Phe Gln Tyr
1 5
<210> 228
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 228
Thr Tyr Ser Ser Gly Asn
1 5
<210> 229
<211> 14
<212> PRT
<213> 智人(Homo sapiens)
<400> 229
Cys Ala Met Thr Ser Pro Tyr Asn Asn Asn Asp Met Arg Phe
1 5 10
<210> 230
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 230
Asp Phe Gln Ala Thr Thr
1 5
<210> 231
<211> 7
<212> PRT
<213> 智人(Homo sapiens)
<400> 231
Ser Asn Glu Gly Ser Lys Ala
1 5
<210> 232
<211> 13
<212> PRT
<213> 智人(Homo sapiens)
<400> 232
Cys Ser Gly Gly Leu Glu Glu Ala Ala Arg Gln Phe Ile
1 5 10
<210> 233
<211> 134
<212> PRT
<213> 智人(Homo sapiens)
<400> 233
Met Ala Lys Ser Leu Arg Val Leu Leu Val Ile Leu Trp Leu Gln Leu
1 5 10 15
Ser Trp Val Trp Ser Gln Gln Lys Glu Val Glu Gln Asp Pro Gly Pro
20 25 30
Leu Ser Val Pro Glu Gly Ala Ile Val Ser Leu Asn Cys Thr Tyr Ser
35 40 45
Asn Ser Ala Phe Gln Tyr Phe Met Trp Tyr Arg Gln Tyr Ser Arg Lys
50 55 60
Gly Pro Glu Leu Leu Met Tyr Thr Tyr Ser Ser Gly Asn Lys Glu Asp
65 70 75 80
Gly Arg Phe Thr Ala Gln Val Asp Lys Ser Ser Lys Tyr Ile Ser Leu
85 90 95
Phe Ile Arg Asp Ser Gln Pro Ser Asp Ser Ala Thr Tyr Leu Cys Ala
100 105 110
Met Thr Ser Pro Tyr Asn Asn Asn Asp Met Arg Phe Gly Ala Gly Thr
115 120 125
Arg Leu Thr Val Lys Pro
130
<210> 234
<211> 140
<212> PRT
<213> 智人(Homo sapiens)
<400> 234
Met His Leu Leu Leu Leu Leu Leu Gly Pro Gly Ile Ser Leu Leu Leu
1 5 10 15
Pro Gly Ser Leu Ala Gly Ser Gly Leu Gly Ala Val Val Ser Gln His
20 25 30
Pro Ser Trp Val Ile Cys Lys Ser Gly Thr Ser Val Lys Ile Glu Cys
35 40 45
Arg Ser Leu Asp Phe Gln Ala Thr Thr Met Phe Trp Tyr Arg Gln Phe
50 55 60
Pro Lys Gln Ser Leu Met Leu Met Ala Thr Ser Asn Glu Gly Ser Lys
65 70 75 80
Ala Thr Tyr Glu Gln Gly Val Glu Lys Asp Lys Phe Leu Ile Asn His
85 90 95
Ala Ser Leu Thr Leu Ser Thr Leu Thr Val Thr Ser Ala His Pro Glu
100 105 110
Asp Ser Ser Phe Tyr Ile Cys Ser Gly Gly Leu Glu Glu Ala Ala Arg
115 120 125
Gln Phe Ile Gly Pro Gly Thr Arg Leu Thr Val Leu
130 135 140
<210> 235
<211> 271
<212> PRT
<213> 智人(Homo sapiens)
<400> 235
Met Ala Lys Ser Leu Arg Val Leu Leu Val Ile Leu Trp Leu Gln Leu
1 5 10 15
Ser Trp Val Trp Ser Gln Gln Lys Glu Val Glu Gln Asp Pro Gly Pro
20 25 30
Leu Ser Val Pro Glu Gly Ala Ile Val Ser Leu Asn Cys Thr Tyr Ser
35 40 45
Asn Ser Ala Phe Gln Tyr Phe Met Trp Tyr Arg Gln Tyr Ser Arg Lys
50 55 60
Gly Pro Glu Leu Leu Met Tyr Thr Tyr Ser Ser Gly Asn Lys Glu Asp
65 70 75 80
Gly Arg Phe Thr Ala Gln Val Asp Lys Ser Ser Lys Tyr Ile Ser Leu
85 90 95
Phe Ile Arg Asp Ser Gln Pro Ser Asp Ser Ala Thr Tyr Leu Cys Ala
100 105 110
Met Thr Ser Pro Tyr Asn Asn Asn Asp Met Arg Phe Gly Ala Gly Thr
115 120 125
Arg Leu Thr Val Lys Pro Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr
130 135 140
Gln Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr
145 150 155 160
Asp Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr
165 170 175
Phe Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys
180 185 190
Ser Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln
195 200 205
Asp Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro
210 215 220
Cys Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu
225 230 235 240
Asn Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys
245 250 255
Val Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser
260 265 270
<210> 236
<211> 313
<212> PRT
<213> 智人(Homo sapiens)
<400> 236
Met His Leu Leu Leu Leu Leu Leu Gly Pro Gly Ile Ser Leu Leu Leu
1 5 10 15
Pro Gly Ser Leu Ala Gly Ser Gly Leu Gly Ala Val Val Ser Gln His
20 25 30
Pro Ser Trp Val Ile Cys Lys Ser Gly Thr Ser Val Lys Ile Glu Cys
35 40 45
Arg Ser Leu Asp Phe Gln Ala Thr Thr Met Phe Trp Tyr Arg Gln Phe
50 55 60
Pro Lys Gln Ser Leu Met Leu Met Ala Thr Ser Asn Glu Gly Ser Lys
65 70 75 80
Ala Thr Tyr Glu Gln Gly Val Glu Lys Asp Lys Phe Leu Ile Asn His
85 90 95
Ala Ser Leu Thr Leu Ser Thr Leu Thr Val Thr Ser Ala His Pro Glu
100 105 110
Asp Ser Ser Phe Tyr Ile Cys Ser Gly Gly Leu Glu Glu Ala Ala Arg
115 120 125
Gln Phe Ile Gly Pro Gly Thr Arg Leu Thr Val Leu Glu Asp Leu Arg
130 135 140
Asn Val Thr Pro Pro Lys Val Ser Leu Phe Glu Pro Ser Lys Ala Glu
145 150 155 160
Ile Ala Asn Lys Gln Lys Ala Thr Leu Val Cys Leu Ala Arg Gly Phe
165 170 175
Phe Pro Asp His Val Glu Leu Ser Trp Trp Val Asn Gly Lys Glu Val
180 185 190
His Ser Gly Val Cys Thr Asp Pro Gln Ala Tyr Lys Glu Ser Asn Tyr
195 200 205
Ser Tyr Cys Leu Ser Ser Arg Leu Arg Val Ser Ala Thr Phe Trp His
210 215 220
Asn Pro Arg Asn His Phe Arg Cys Gln Val Gln Phe His Gly Leu Ser
225 230 235 240
Glu Glu Asp Lys Trp Pro Glu Gly Ser Pro Lys Pro Val Thr Gln Asn
245 250 255
Ile Ser Ala Glu Ala Trp Gly Arg Ala Asp Cys Gly Ile Thr Ser Ala
260 265 270
Ser Tyr Gln Gln Gly Val Leu Ser Ala Thr Ile Leu Tyr Glu Ile Leu
275 280 285
Leu Gly Lys Ala Thr Leu Tyr Ala Val Leu Val Ser Thr Leu Val Val
290 295 300
Met Ala Met Val Lys Arg Lys Asn Ser
305 310
<210> 237
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 237
Asn Ser Ala Phe Gln Tyr
1 5
<210> 238
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 238
Thr Tyr Ser Ser Gly Asn
1 5
<210> 239
<211> 14
<212> PRT
<213> 智人(Homo sapiens)
<400> 239
Cys Ala Met Thr Ser Pro Tyr Asn Asn Asn Asp Met Arg Phe
1 5 10
<210> 240
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 240
Asp Phe Gln Ala Thr Thr
1 5
<210> 241
<211> 7
<212> PRT
<213> 智人(Homo sapiens)
<400> 241
Ser Asn Glu Gly Ser Lys Ala
1 5
<210> 242
<211> 13
<212> PRT
<213> 智人(Homo sapiens)
<400> 242
Cys Ser Gly Gly Leu Glu Glu Ala Ala Arg Gln Phe Ile
1 5 10
<210> 243
<211> 134
<212> PRT
<213> 智人(Homo sapiens)
<400> 243
Met Ala Lys Ser Leu Arg Val Leu Leu Val Ile Leu Trp Leu Gln Leu
1 5 10 15
Ser Trp Val Trp Ser Gln Gln Lys Glu Val Glu Gln Asp Pro Gly Pro
20 25 30
Leu Ser Val Pro Glu Gly Ala Ile Val Ser Leu Asn Cys Thr Tyr Ser
35 40 45
Asn Ser Ala Phe Gln Tyr Phe Met Trp Tyr Arg Gln Tyr Ser Arg Lys
50 55 60
Gly Pro Glu Leu Leu Met Tyr Thr Tyr Ser Ser Gly Asn Lys Glu Asp
65 70 75 80
Gly Arg Phe Thr Ala Gln Val Asp Lys Ser Ser Lys Tyr Ile Ser Leu
85 90 95
Phe Ile Arg Asp Ser Gln Pro Ser Asp Ser Ala Thr Tyr Leu Cys Ala
100 105 110
Met Thr Ser Pro Tyr Asn Asn Asn Asp Met Arg Phe Gly Ala Gly Thr
115 120 125
Arg Leu Thr Val Lys Pro
130
<210> 244
<211> 130
<212> PRT
<213> 智人(Homo sapiens)
<400> 244
Met His Leu Leu Leu Leu Leu Leu Gly Pro Ala Gly Ser Gly Leu Gly
1 5 10 15
Ala Val Val Ser Gln His Pro Ser Arg Val Ile Cys Lys Ser Gly Thr
20 25 30
Ser Val Lys Ile Glu Cys Arg Ser Leu Asp Phe Gln Ala Thr Thr Met
35 40 45
Phe Trp Tyr Arg Gln Phe Pro Lys Gln Ser Leu Met Leu Met Ala Thr
50 55 60
Ser Asn Glu Gly Ser Lys Ala Thr Tyr Glu Gln Gly Val Glu Lys Asp
65 70 75 80
Lys Phe Leu Ile Asn His Ala Ser Leu Thr Leu Ser Thr Leu Thr Val
85 90 95
Thr Ser Ala His Pro Glu Asp Ser Ser Phe Tyr Ile Cys Ser Gly Gly
100 105 110
Leu Glu Glu Ala Ala Arg Gln Phe Ile Gly Pro Gly Thr Arg Leu Thr
115 120 125
Val Leu
130
<210> 245
<211> 271
<212> PRT
<213> 智人(Homo sapiens)
<400> 245
Met Ala Lys Ser Leu Arg Val Leu Leu Val Ile Leu Trp Leu Gln Leu
1 5 10 15
Ser Trp Val Trp Ser Gln Gln Lys Glu Val Glu Gln Asp Pro Gly Pro
20 25 30
Leu Ser Val Pro Glu Gly Ala Ile Val Ser Leu Asn Cys Thr Tyr Ser
35 40 45
Asn Ser Ala Phe Gln Tyr Phe Met Trp Tyr Arg Gln Tyr Ser Arg Lys
50 55 60
Gly Pro Glu Leu Leu Met Tyr Thr Tyr Ser Ser Gly Asn Lys Glu Asp
65 70 75 80
Gly Arg Phe Thr Ala Gln Val Asp Lys Ser Ser Lys Tyr Ile Ser Leu
85 90 95
Phe Ile Arg Asp Ser Gln Pro Ser Asp Ser Ala Thr Tyr Leu Cys Ala
100 105 110
Met Thr Ser Pro Tyr Asn Asn Asn Asp Met Arg Phe Gly Ala Gly Thr
115 120 125
Arg Leu Thr Val Lys Pro Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr
130 135 140
Gln Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr
145 150 155 160
Asp Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr
165 170 175
Phe Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys
180 185 190
Ser Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln
195 200 205
Asp Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro
210 215 220
Cys Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu
225 230 235 240
Asn Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys
245 250 255
Val Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser
260 265 270
<210> 246
<211> 303
<212> PRT
<213> 智人(Homo sapiens)
<400> 246
Met His Leu Leu Leu Leu Leu Leu Gly Pro Ala Gly Ser Gly Leu Gly
1 5 10 15
Ala Val Val Ser Gln His Pro Ser Arg Val Ile Cys Lys Ser Gly Thr
20 25 30
Ser Val Lys Ile Glu Cys Arg Ser Leu Asp Phe Gln Ala Thr Thr Met
35 40 45
Phe Trp Tyr Arg Gln Phe Pro Lys Gln Ser Leu Met Leu Met Ala Thr
50 55 60
Ser Asn Glu Gly Ser Lys Ala Thr Tyr Glu Gln Gly Val Glu Lys Asp
65 70 75 80
Lys Phe Leu Ile Asn His Ala Ser Leu Thr Leu Ser Thr Leu Thr Val
85 90 95
Thr Ser Ala His Pro Glu Asp Ser Ser Phe Tyr Ile Cys Ser Gly Gly
100 105 110
Leu Glu Glu Ala Ala Arg Gln Phe Ile Gly Pro Gly Thr Arg Leu Thr
115 120 125
Val Leu Glu Asp Leu Arg Asn Val Thr Pro Pro Lys Val Ser Leu Phe
130 135 140
Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys Ala Thr Leu Val
145 150 155 160
Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu Leu Ser Trp Trp
165 170 175
Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr Asp Pro Gln Ala
180 185 190
Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser Arg Leu Arg Val
195 200 205
Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe Arg Cys Gln Val
210 215 220
Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro Glu Gly Ser Pro
225 230 235 240
Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp Gly Arg Ala Asp
245 250 255
Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val Leu Ser Ala Thr
260 265 270
Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu Tyr Ala Val Leu
275 280 285
Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg Lys Asn Ser
290 295 300
<210> 247
<211> 7
<212> PRT
<213> 智人(Homo sapiens)
<400> 247
Thr Ile Ser Gly Asn Glu Tyr
1 5
<210> 248
<211> 5
<212> PRT
<213> 智人(Homo sapiens)
<400> 248
Gly Leu Lys Asn Asn
1 5
<210> 249
<211> 11
<212> PRT
<213> 智人(Homo sapiens)
<400> 249
Cys Ile Val Pro Asn Asp Tyr Lys Leu Ser Phe
1 5 10
<210> 250
<211> 5
<212> PRT
<213> 智人(Homo sapiens)
<400> 250
Met Asp His Glu Asn
1 5
<210> 251
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 251
Ser Tyr Asp Val Lys Met
1 5
<210> 252
<211> 16
<212> PRT
<213> 智人(Homo sapiens)
<400> 252
Cys Ala Ser Ser Phe Gly Thr Gly Ser Ile Gln Glu Thr Gln Tyr Phe
1 5 10 15
<210> 253
<211> 125
<212> PRT
<213> 智人(Homo sapiens)
<400> 253
Met Ala Leu Val Ala Arg Val Thr Val Phe Leu Thr Phe Gly Thr Ile
1 5 10 15
Ile Asp Ala Lys Thr Thr Gln Pro Pro Ser Met Asp Cys Ala Glu Gly
20 25 30
Arg Ala Ala Asn Leu Pro Cys Asn His Ser Thr Ile Ser Gly Asn Glu
35 40 45
Tyr Val Tyr Trp Tyr Arg Gln Ile His Ser Gln Gly Pro Gln Tyr Ile
50 55 60
Ile His Gly Leu Lys Asn Asn Glu Thr Asn Glu Met Ala Ser Leu Ile
65 70 75 80
Ile Thr Glu Asp Arg Lys Ser Ser Thr Leu Ile Leu Pro His Ala Thr
85 90 95
Leu Arg Asp Thr Ala Val Tyr Tyr Cys Ile Val Pro Asn Asp Tyr Lys
100 105 110
Leu Ser Phe Gly Ala Gly Thr Thr Val Thr Val Arg Ala
115 120 125
<210> 254
<211> 134
<212> PRT
<213> 智人(Homo sapiens)
<400> 254
Met His Ile Arg Leu Leu Cys Arg Val Ala Phe Cys Phe Leu Ala Val
1 5 10 15
Gly Leu Val Asp Val Lys Val Thr Gln Ser Ser Arg Tyr Leu Val Lys
20 25 30
Arg Thr Gly Glu Lys Val Phe Leu Glu Cys Val Gln Asp Met Asp His
35 40 45
Glu Asn Met Phe Trp Tyr Arg Gln Asp Pro Gly Leu Gly Leu Arg Leu
50 55 60
Ile Tyr Phe Ser Tyr Asp Val Lys Met Lys Glu Lys Gly Asp Ile Pro
65 70 75 80
Glu Gly Tyr Ser Val Ser Arg Glu Lys Lys Glu Arg Phe Ser Leu Ile
85 90 95
Leu Glu Ser Ala Ser Thr Asn Gln Thr Ser Met Tyr Leu Cys Ala Ser
100 105 110
Ser Phe Gly Thr Gly Ser Ile Gln Glu Thr Gln Tyr Phe Gly Pro Gly
115 120 125
Thr Arg Leu Leu Val Leu
130
<210> 255
<211> 262
<212> PRT
<213> 智人(Homo sapiens)
<400> 255
Met Ala Leu Val Ala Arg Val Thr Val Phe Leu Thr Phe Gly Thr Ile
1 5 10 15
Ile Asp Ala Lys Thr Thr Gln Pro Pro Ser Met Asp Cys Ala Glu Gly
20 25 30
Arg Ala Ala Asn Leu Pro Cys Asn His Ser Thr Ile Ser Gly Asn Glu
35 40 45
Tyr Val Tyr Trp Tyr Arg Gln Ile His Ser Gln Gly Pro Gln Tyr Ile
50 55 60
Ile His Gly Leu Lys Asn Asn Glu Thr Asn Glu Met Ala Ser Leu Ile
65 70 75 80
Ile Thr Glu Asp Arg Lys Ser Ser Thr Leu Ile Leu Pro His Ala Thr
85 90 95
Leu Arg Asp Thr Ala Val Tyr Tyr Cys Ile Val Pro Asn Asp Tyr Lys
100 105 110
Leu Ser Phe Gly Ala Gly Thr Thr Val Thr Val Arg Ala Asn Ile Gln
115 120 125
Asn Pro Glu Pro Ala Val Tyr Gln Leu Lys Asp Pro Arg Ser Gln Asp
130 135 140
Ser Thr Leu Cys Leu Phe Thr Asp Phe Asp Ser Gln Ile Asn Val Pro
145 150 155 160
Lys Thr Met Glu Ser Gly Thr Phe Ile Thr Asp Lys Cys Val Leu Asp
165 170 175
Met Lys Ala Met Asp Ser Lys Ser Asn Gly Ala Ile Ala Trp Ser Asn
180 185 190
Gln Thr Ser Phe Thr Cys Gln Asp Ile Phe Lys Glu Thr Asn Ala Thr
195 200 205
Tyr Pro Ser Ser Asp Val Pro Cys Asp Ala Thr Leu Thr Glu Lys Ser
210 215 220
Phe Glu Thr Asp Met Asn Leu Asn Phe Gln Asn Leu Leu Val Ile Val
225 230 235 240
Leu Arg Ile Leu Leu Leu Lys Val Ala Gly Phe Asn Leu Leu Met Thr
245 250 255
Leu Arg Leu Trp Ser Ser
260
<210> 256
<211> 307
<212> PRT
<213> 智人(Homo sapiens)
<400> 256
Met His Ile Arg Leu Leu Cys Arg Val Ala Phe Cys Phe Leu Ala Val
1 5 10 15
Gly Leu Val Asp Val Lys Val Thr Gln Ser Ser Arg Tyr Leu Val Lys
20 25 30
Arg Thr Gly Glu Lys Val Phe Leu Glu Cys Val Gln Asp Met Asp His
35 40 45
Glu Asn Met Phe Trp Tyr Arg Gln Asp Pro Gly Leu Gly Leu Arg Leu
50 55 60
Ile Tyr Phe Ser Tyr Asp Val Lys Met Lys Glu Lys Gly Asp Ile Pro
65 70 75 80
Glu Gly Tyr Ser Val Ser Arg Glu Lys Lys Glu Arg Phe Ser Leu Ile
85 90 95
Leu Glu Ser Ala Ser Thr Asn Gln Thr Ser Met Tyr Leu Cys Ala Ser
100 105 110
Ser Phe Gly Thr Gly Ser Ile Gln Glu Thr Gln Tyr Phe Gly Pro Gly
115 120 125
Thr Arg Leu Leu Val Leu Glu Asp Leu Arg Asn Val Thr Pro Pro Lys
130 135 140
Val Ser Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys
145 150 155 160
Ala Thr Leu Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu
165 170 175
Leu Ser Trp Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr
180 185 190
Asp Pro Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser
195 200 205
Arg Leu Arg Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe
210 215 220
Arg Cys Gln Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro
225 230 235 240
Glu Gly Ser Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp
245 250 255
Gly Arg Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val
260 265 270
Leu Ser Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu
275 280 285
Tyr Ala Val Leu Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg
290 295 300
Lys Asn Ser
305
<210> 257
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 257
Ala Thr Gly Tyr Pro Ser
1 5
<210> 258
<211> 7
<212> PRT
<213> 智人(Homo sapiens)
<400> 258
Ala Thr Lys Ala Asp Asp Lys
1 5
<210> 259
<211> 17
<212> PRT
<213> 智人(Homo sapiens)
<400> 259
Cys Ala Leu Asn Pro Asn Ala Gly Gly Thr Ser Tyr Gly Lys Leu Thr
1 5 10 15
Phe
<210> 260
<211> 5
<212> PRT
<213> 智人(Homo sapiens)
<400> 260
Ser Gly His Thr Ser
1 5
<210> 261
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 261
Tyr Asp Glu Gly Glu Glu
1 5
<210> 262
<211> 20
<212> PRT
<213> 智人(Homo sapiens)
<400> 262
Cys Ala Ser Ser Ser Pro Gly Ala Thr Ser Gly Gly Ala Asn Thr Gly
1 5 10 15
Glu Leu Phe Phe
20
<210> 263
<211> 135
<212> PRT
<213> 智人(Homo sapiens)
<400> 263
Met Ala Tyr Ser Pro Gly Leu Val Ser Leu Ile Leu Leu Leu Leu Gly
1 5 10 15
Arg Thr Arg Gly Asn Ser Val Thr Gln Met Glu Gly Pro Val Thr Leu
20 25 30
Ser Glu Glu Ala Phe Leu Thr Ile Asn Cys Thr Tyr Thr Ala Thr Gly
35 40 45
Tyr Pro Ser Leu Phe Trp Tyr Val Gln Tyr Pro Gly Glu Gly Leu Gln
50 55 60
Leu Leu Leu Lys Ala Thr Lys Ala Asp Asp Lys Gly Ser Asn Lys Gly
65 70 75 80
Phe Glu Ala Thr Tyr Arg Lys Glu Thr Thr Ser Phe His Leu Glu Lys
85 90 95
Gly Ser Val Gln Val Ser Asp Ser Ala Val Tyr Phe Cys Ala Leu Asn
100 105 110
Pro Asn Ala Gly Gly Thr Ser Tyr Gly Lys Leu Thr Phe Gly Gln Gly
115 120 125
Thr Ile Leu Thr Val His Pro
130 135
<210> 264
<211> 138
<212> PRT
<213> 智人(Homo sapiens)
<400> 264
Met His Pro Arg Leu Leu Phe Trp Ala Leu Leu Cys Leu Leu Gly Thr
1 5 10 15
Gly Pro Val Glu Ala Gly Val Thr Gln Ser Pro Thr His Leu Ile Lys
20 25 30
Thr Arg Gly Gln Gln Ala Thr Leu Arg Cys Ser Pro Ile Ser Gly His
35 40 45
Thr Ser Val Tyr Trp Tyr Gln Gln Ala Leu Gly Leu Gly Leu Gln Phe
50 55 60
Leu Leu Trp Tyr Asp Glu Gly Glu Glu Arg Asn Arg Gly Asn Phe Pro
65 70 75 80
Pro Arg Phe Ser Gly Arg Gln Phe Pro Asn Tyr Ser Ser Glu Leu Asn
85 90 95
Val Asn Ala Leu Glu Leu Glu Asp Ser Ala Leu Tyr Leu Cys Ala Ser
100 105 110
Ser Ser Pro Gly Ala Thr Ser Gly Gly Ala Asn Thr Gly Glu Leu Phe
115 120 125
Phe Gly Glu Gly Ser Arg Leu Thr Val Leu
130 135
<210> 265
<211> 272
<212> PRT
<213> 智人(Homo sapiens)
<400> 265
Met Ala Tyr Ser Pro Gly Leu Val Ser Leu Ile Leu Leu Leu Leu Gly
1 5 10 15
Arg Thr Arg Gly Asn Ser Val Thr Gln Met Glu Gly Pro Val Thr Leu
20 25 30
Ser Glu Glu Ala Phe Leu Thr Ile Asn Cys Thr Tyr Thr Ala Thr Gly
35 40 45
Tyr Pro Ser Leu Phe Trp Tyr Val Gln Tyr Pro Gly Glu Gly Leu Gln
50 55 60
Leu Leu Leu Lys Ala Thr Lys Ala Asp Asp Lys Gly Ser Asn Lys Gly
65 70 75 80
Phe Glu Ala Thr Tyr Arg Lys Glu Thr Thr Ser Phe His Leu Glu Lys
85 90 95
Gly Ser Val Gln Val Ser Asp Ser Ala Val Tyr Phe Cys Ala Leu Asn
100 105 110
Pro Asn Ala Gly Gly Thr Ser Tyr Gly Lys Leu Thr Phe Gly Gln Gly
115 120 125
Thr Ile Leu Thr Val His Pro Asn Ile Gln Asn Pro Glu Pro Ala Val
130 135 140
Tyr Gln Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe
145 150 155 160
Thr Asp Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly
165 170 175
Thr Phe Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser
180 185 190
Lys Ser Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys
195 200 205
Gln Asp Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val
210 215 220
Pro Cys Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn
225 230 235 240
Leu Asn Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu
245 250 255
Lys Val Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser
260 265 270
<210> 266
<211> 311
<212> PRT
<213> 智人(Homo sapiens)
<400> 266
Met His Pro Arg Leu Leu Phe Trp Ala Leu Leu Cys Leu Leu Gly Thr
1 5 10 15
Gly Pro Val Glu Ala Gly Val Thr Gln Ser Pro Thr His Leu Ile Lys
20 25 30
Thr Arg Gly Gln Gln Ala Thr Leu Arg Cys Ser Pro Ile Ser Gly His
35 40 45
Thr Ser Val Tyr Trp Tyr Gln Gln Ala Leu Gly Leu Gly Leu Gln Phe
50 55 60
Leu Leu Trp Tyr Asp Glu Gly Glu Glu Arg Asn Arg Gly Asn Phe Pro
65 70 75 80
Pro Arg Phe Ser Gly Arg Gln Phe Pro Asn Tyr Ser Ser Glu Leu Asn
85 90 95
Val Asn Ala Leu Glu Leu Glu Asp Ser Ala Leu Tyr Leu Cys Ala Ser
100 105 110
Ser Ser Pro Gly Ala Thr Ser Gly Gly Ala Asn Thr Gly Glu Leu Phe
115 120 125
Phe Gly Glu Gly Ser Arg Leu Thr Val Leu Glu Asp Leu Arg Asn Val
130 135 140
Thr Pro Pro Lys Val Ser Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala
145 150 155 160
Asn Lys Gln Lys Ala Thr Leu Val Cys Leu Ala Arg Gly Phe Phe Pro
165 170 175
Asp His Val Glu Leu Ser Trp Trp Val Asn Gly Lys Glu Val His Ser
180 185 190
Gly Val Cys Thr Asp Pro Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr
195 200 205
Cys Leu Ser Ser Arg Leu Arg Val Ser Ala Thr Phe Trp His Asn Pro
210 215 220
Arg Asn His Phe Arg Cys Gln Val Gln Phe His Gly Leu Ser Glu Glu
225 230 235 240
Asp Lys Trp Pro Glu Gly Ser Pro Lys Pro Val Thr Gln Asn Ile Ser
245 250 255
Ala Glu Ala Trp Gly Arg Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr
260 265 270
Gln Gln Gly Val Leu Ser Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly
275 280 285
Lys Ala Thr Leu Tyr Ala Val Leu Val Ser Thr Leu Val Val Met Ala
290 295 300
Met Val Lys Arg Lys Asn Ser
305 310
<210> 267
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 267
Asp Ser Ser Ser Thr Tyr
1 5
<210> 268
<211> 7
<212> PRT
<213> 智人(Homo sapiens)
<400> 268
Ile Phe Ser Asn Met Asp Met
1 5
<210> 269
<211> 17
<212> PRT
<213> 智人(Homo sapiens)
<400> 269
Cys Ala Glu Ile Pro Arg Asp Ser Gly Gly Gly Ala Asp Gly Leu Thr
1 5 10 15
Phe
<210> 270
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 270
Asp Phe Gln Ala Thr Thr
1 5
<210> 271
<211> 7
<212> PRT
<213> 智人(Homo sapiens)
<400> 271
Ser Asn Glu Gly Ser Lys Ala
1 5
<210> 272
<211> 14
<212> PRT
<213> 智人(Homo sapiens)
<400> 272
Cys Ser Ala Arg Asp Leu Gln Arg Ser Tyr Glu Gln Tyr Phe
1 5 10
<210> 273
<211> 136
<212> PRT
<213> 智人(Homo sapiens)
<400> 273
Met Ala Thr Phe Ala Gly Phe Ser Phe Leu Phe Leu Trp Leu Gln Leu
1 5 10 15
Asp Cys Met Ser Arg Gly Glu Asp Val Glu Gln Ser Leu Phe Leu Ser
20 25 30
Val Arg Glu Gly Asp Ser Ser Val Ile Asn Cys Thr Tyr Thr Asp Ser
35 40 45
Ser Ser Thr Tyr Leu Tyr Trp Tyr Lys Gln Glu Pro Gly Ala Gly Leu
50 55 60
Gln Leu Leu Thr Tyr Ile Phe Ser Asn Met Asp Met Lys Gln Asp Gln
65 70 75 80
Arg Leu Thr Val Leu Leu Asn Lys Lys Asp Lys His Leu Ser Leu Arg
85 90 95
Ile Ala Asp Thr Gln Thr Gly Asp Ser Ala Ile Tyr Phe Cys Ala Glu
100 105 110
Ile Pro Arg Asp Ser Gly Gly Gly Ala Asp Gly Leu Thr Phe Gly Lys
115 120 125
Gly Thr His Leu Ile Ile Gln Pro
130 135
<210> 274
<211> 141
<212> PRT
<213> 智人(Homo sapiens)
<400> 274
Met His Leu Leu Leu Leu Leu Leu Gly Pro Gly Ile Ser Leu Leu Leu
1 5 10 15
Pro Gly Ser Leu Ala Gly Ser Gly Leu Gly Ala Val Val Ser Gln His
20 25 30
Pro Ser Trp Val Ile Cys Lys Ser Gly Thr Ser Val Lys Ile Glu Cys
35 40 45
Arg Ser Leu Asp Phe Gln Ala Thr Thr Met Phe Trp Tyr Arg Gln Phe
50 55 60
Pro Lys Gln Ser Leu Met Leu Met Ala Thr Ser Asn Glu Gly Ser Lys
65 70 75 80
Ala Thr Tyr Glu Gln Gly Val Glu Lys Asp Lys Phe Leu Ile Asn His
85 90 95
Ala Ser Leu Thr Leu Ser Thr Leu Thr Val Thr Ser Ala His Pro Glu
100 105 110
Asp Ser Ser Phe Tyr Ile Cys Ser Ala Arg Asp Leu Gln Arg Ser Tyr
115 120 125
Glu Gln Tyr Phe Gly Pro Gly Thr Arg Leu Thr Val Thr
130 135 140
<210> 275
<211> 273
<212> PRT
<213> 智人(Homo sapiens)
<400> 275
Met Ala Thr Phe Ala Gly Phe Ser Phe Leu Phe Leu Trp Leu Gln Leu
1 5 10 15
Asp Cys Met Ser Arg Gly Glu Asp Val Glu Gln Ser Leu Phe Leu Ser
20 25 30
Val Arg Glu Gly Asp Ser Ser Val Ile Asn Cys Thr Tyr Thr Asp Ser
35 40 45
Ser Ser Thr Tyr Leu Tyr Trp Tyr Lys Gln Glu Pro Gly Ala Gly Leu
50 55 60
Gln Leu Leu Thr Tyr Ile Phe Ser Asn Met Asp Met Lys Gln Asp Gln
65 70 75 80
Arg Leu Thr Val Leu Leu Asn Lys Lys Asp Lys His Leu Ser Leu Arg
85 90 95
Ile Ala Asp Thr Gln Thr Gly Asp Ser Ala Ile Tyr Phe Cys Ala Glu
100 105 110
Ile Pro Arg Asp Ser Gly Gly Gly Ala Asp Gly Leu Thr Phe Gly Lys
115 120 125
Gly Thr His Leu Ile Ile Gln Pro Asn Ile Gln Asn Pro Glu Pro Ala
130 135 140
Val Tyr Gln Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu
145 150 155 160
Phe Thr Asp Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser
165 170 175
Gly Thr Phe Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp
180 185 190
Ser Lys Ser Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr
195 200 205
Cys Gln Asp Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp
210 215 220
Val Pro Cys Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met
225 230 235 240
Asn Leu Asn Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu
245 250 255
Leu Lys Val Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser
260 265 270
Ser
<210> 276
<211> 314
<212> PRT
<213> 智人(Homo sapiens)
<400> 276
Met His Leu Leu Leu Leu Leu Leu Gly Pro Gly Ile Ser Leu Leu Leu
1 5 10 15
Pro Gly Ser Leu Ala Gly Ser Gly Leu Gly Ala Val Val Ser Gln His
20 25 30
Pro Ser Trp Val Ile Cys Lys Ser Gly Thr Ser Val Lys Ile Glu Cys
35 40 45
Arg Ser Leu Asp Phe Gln Ala Thr Thr Met Phe Trp Tyr Arg Gln Phe
50 55 60
Pro Lys Gln Ser Leu Met Leu Met Ala Thr Ser Asn Glu Gly Ser Lys
65 70 75 80
Ala Thr Tyr Glu Gln Gly Val Glu Lys Asp Lys Phe Leu Ile Asn His
85 90 95
Ala Ser Leu Thr Leu Ser Thr Leu Thr Val Thr Ser Ala His Pro Glu
100 105 110
Asp Ser Ser Phe Tyr Ile Cys Ser Ala Arg Asp Leu Gln Arg Ser Tyr
115 120 125
Glu Gln Tyr Phe Gly Pro Gly Thr Arg Leu Thr Val Thr Glu Asp Leu
130 135 140
Arg Asn Val Thr Pro Pro Lys Val Ser Leu Phe Glu Pro Ser Lys Ala
145 150 155 160
Glu Ile Ala Asn Lys Gln Lys Ala Thr Leu Val Cys Leu Ala Arg Gly
165 170 175
Phe Phe Pro Asp His Val Glu Leu Ser Trp Trp Val Asn Gly Lys Glu
180 185 190
Val His Ser Gly Val Cys Thr Asp Pro Gln Ala Tyr Lys Glu Ser Asn
195 200 205
Tyr Ser Tyr Cys Leu Ser Ser Arg Leu Arg Val Ser Ala Thr Phe Trp
210 215 220
His Asn Pro Arg Asn His Phe Arg Cys Gln Val Gln Phe His Gly Leu
225 230 235 240
Ser Glu Glu Asp Lys Trp Pro Glu Gly Ser Pro Lys Pro Val Thr Gln
245 250 255
Asn Ile Ser Ala Glu Ala Trp Gly Arg Ala Asp Cys Gly Ile Thr Ser
260 265 270
Ala Ser Tyr Gln Gln Gly Val Leu Ser Ala Thr Ile Leu Tyr Glu Ile
275 280 285
Leu Leu Gly Lys Ala Thr Leu Tyr Ala Val Leu Val Ser Thr Leu Val
290 295 300
Val Met Ala Met Val Lys Arg Lys Asn Ser
305 310
<210> 277
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 277
Asp Ser Ser Ser Thr Tyr
1 5
<210> 278
<211> 7
<212> PRT
<213> 智人(Homo sapiens)
<400> 278
Ile Phe Ser Asn Met Asp Met
1 5
<210> 279
<211> 17
<212> PRT
<213> 智人(Homo sapiens)
<400> 279
Cys Ala Glu Ile Pro Arg Asp Ser Gly Gly Gly Ala Asp Gly Leu Thr
1 5 10 15
Phe
<210> 280
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 280
Asp Phe Gln Ala Thr Thr
1 5
<210> 281
<211> 7
<212> PRT
<213> 智人(Homo sapiens)
<400> 281
Ser Asn Glu Gly Ser Lys Ala
1 5
<210> 282
<211> 14
<212> PRT
<213> 智人(Homo sapiens)
<400> 282
Cys Ser Ala Arg Asp Leu Gln Arg Ser Tyr Glu Gln Tyr Phe
1 5 10
<210> 283
<211> 136
<212> PRT
<213> 智人(Homo sapiens)
<400> 283
Met Ala Thr Phe Ala Gly Phe Ser Phe Leu Phe Leu Trp Leu Gln Leu
1 5 10 15
Asp Cys Met Ser Arg Gly Glu Asp Val Glu Gln Ser Leu Phe Leu Ser
20 25 30
Val Arg Glu Gly Asp Ser Ser Val Ile Asn Cys Thr Tyr Thr Asp Ser
35 40 45
Ser Ser Thr Tyr Leu Tyr Trp Tyr Lys Gln Glu Pro Gly Ala Gly Leu
50 55 60
Gln Leu Leu Thr Tyr Ile Phe Ser Asn Met Asp Met Lys Gln Asp Gln
65 70 75 80
Arg Leu Thr Val Leu Leu Asn Lys Lys Asp Lys His Leu Ser Leu Arg
85 90 95
Ile Ala Asp Thr Gln Thr Gly Asp Ser Ala Ile Tyr Phe Cys Ala Glu
100 105 110
Ile Pro Arg Asp Ser Gly Gly Gly Ala Asp Gly Leu Thr Phe Gly Lys
115 120 125
Gly Thr His Leu Ile Ile Gln Pro
130 135
<210> 284
<211> 131
<212> PRT
<213> 智人(Homo sapiens)
<400> 284
Met His Leu Leu Leu Leu Leu Leu Gly Pro Ala Gly Ser Gly Leu Gly
1 5 10 15
Ala Val Val Ser Gln His Pro Ser Arg Val Ile Cys Lys Ser Gly Thr
20 25 30
Ser Val Lys Ile Glu Cys Arg Ser Leu Asp Phe Gln Ala Thr Thr Met
35 40 45
Phe Trp Tyr Arg Gln Phe Pro Lys Gln Ser Leu Met Leu Met Ala Thr
50 55 60
Ser Asn Glu Gly Ser Lys Ala Thr Tyr Glu Gln Gly Val Glu Lys Asp
65 70 75 80
Lys Phe Leu Ile Asn His Ala Ser Leu Thr Leu Ser Thr Leu Thr Val
85 90 95
Thr Ser Ala His Pro Glu Asp Ser Ser Phe Tyr Ile Cys Ser Ala Arg
100 105 110
Asp Leu Gln Arg Ser Tyr Glu Gln Tyr Phe Gly Pro Gly Thr Arg Leu
115 120 125
Thr Val Thr
130
<210> 285
<211> 273
<212> PRT
<213> 智人(Homo sapiens)
<400> 285
Met Ala Thr Phe Ala Gly Phe Ser Phe Leu Phe Leu Trp Leu Gln Leu
1 5 10 15
Asp Cys Met Ser Arg Gly Glu Asp Val Glu Gln Ser Leu Phe Leu Ser
20 25 30
Val Arg Glu Gly Asp Ser Ser Val Ile Asn Cys Thr Tyr Thr Asp Ser
35 40 45
Ser Ser Thr Tyr Leu Tyr Trp Tyr Lys Gln Glu Pro Gly Ala Gly Leu
50 55 60
Gln Leu Leu Thr Tyr Ile Phe Ser Asn Met Asp Met Lys Gln Asp Gln
65 70 75 80
Arg Leu Thr Val Leu Leu Asn Lys Lys Asp Lys His Leu Ser Leu Arg
85 90 95
Ile Ala Asp Thr Gln Thr Gly Asp Ser Ala Ile Tyr Phe Cys Ala Glu
100 105 110
Ile Pro Arg Asp Ser Gly Gly Gly Ala Asp Gly Leu Thr Phe Gly Lys
115 120 125
Gly Thr His Leu Ile Ile Gln Pro Asn Ile Gln Asn Pro Glu Pro Ala
130 135 140
Val Tyr Gln Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu
145 150 155 160
Phe Thr Asp Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser
165 170 175
Gly Thr Phe Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp
180 185 190
Ser Lys Ser Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr
195 200 205
Cys Gln Asp Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp
210 215 220
Val Pro Cys Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met
225 230 235 240
Asn Leu Asn Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu
245 250 255
Leu Lys Val Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser
260 265 270
Ser
<210> 286
<211> 304
<212> PRT
<213> 智人(Homo sapiens)
<400> 286
Met His Leu Leu Leu Leu Leu Leu Gly Pro Ala Gly Ser Gly Leu Gly
1 5 10 15
Ala Val Val Ser Gln His Pro Ser Arg Val Ile Cys Lys Ser Gly Thr
20 25 30
Ser Val Lys Ile Glu Cys Arg Ser Leu Asp Phe Gln Ala Thr Thr Met
35 40 45
Phe Trp Tyr Arg Gln Phe Pro Lys Gln Ser Leu Met Leu Met Ala Thr
50 55 60
Ser Asn Glu Gly Ser Lys Ala Thr Tyr Glu Gln Gly Val Glu Lys Asp
65 70 75 80
Lys Phe Leu Ile Asn His Ala Ser Leu Thr Leu Ser Thr Leu Thr Val
85 90 95
Thr Ser Ala His Pro Glu Asp Ser Ser Phe Tyr Ile Cys Ser Ala Arg
100 105 110
Asp Leu Gln Arg Ser Tyr Glu Gln Tyr Phe Gly Pro Gly Thr Arg Leu
115 120 125
Thr Val Thr Glu Asp Leu Arg Asn Val Thr Pro Pro Lys Val Ser Leu
130 135 140
Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys Ala Thr Leu
145 150 155 160
Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu Leu Ser Trp
165 170 175
Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr Asp Pro Gln
180 185 190
Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser Arg Leu Arg
195 200 205
Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe Arg Cys Gln
210 215 220
Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro Glu Gly Ser
225 230 235 240
Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp Gly Arg Ala
245 250 255
Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val Leu Ser Ala
260 265 270
Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu Tyr Ala Val
275 280 285
Leu Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg Lys Asn Ser
290 295 300
<210> 287
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 287
Asn Ser Ala Ser Asp Tyr
1 5
<210> 288
<211> 7
<212> PRT
<213> 智人(Homo sapiens)
<400> 288
Ile Arg Ser Asn Met Asp Lys
1 5
<210> 289
<211> 16
<212> PRT
<213> 智人(Homo sapiens)
<400> 289
Cys Ala Glu Pro Val Gly Gly Leu Asn Ser Gly Tyr Ala Leu Asn Phe
1 5 10 15
<210> 290
<211> 5
<212> PRT
<213> 智人(Homo sapiens)
<400> 290
Ser Gly His Lys Ser
1 5
<210> 291
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 291
Tyr Tyr Glu Lys Glu Glu
1 5
<210> 292
<211> 16
<212> PRT
<213> 智人(Homo sapiens)
<400> 292
Cys Ala Ser Ser Gly Gly Arg Thr Ser Gly Ala Tyr Glu Gln Phe Phe
1 5 10 15
<210> 293
<211> 135
<212> PRT
<213> 智人(Homo sapiens)
<400> 293
Met Ala Gly Ile Arg Ala Leu Phe Met Tyr Leu Trp Leu Gln Leu Asp
1 5 10 15
Trp Val Ser Arg Gly Glu Ser Val Gly Leu His Leu Pro Thr Leu Ser
20 25 30
Val Gln Glu Gly Asp Asn Ser Ile Ile Asn Cys Ala Tyr Ser Asn Ser
35 40 45
Ala Ser Asp Tyr Phe Ile Trp Tyr Lys Gln Glu Ser Gly Lys Gly Pro
50 55 60
Gln Phe Ile Ile Asp Ile Arg Ser Asn Met Asp Lys Arg Gln Gly Gln
65 70 75 80
Arg Val Thr Val Leu Leu Asn Lys Thr Val Lys His Leu Ser Leu Gln
85 90 95
Ile Ala Ala Thr Gln Pro Gly Asp Ser Ala Val Tyr Phe Cys Ala Glu
100 105 110
Pro Val Gly Gly Leu Asn Ser Gly Tyr Ala Leu Asn Phe Gly Lys Gly
115 120 125
Thr Ser Leu Leu Val Thr Pro
130 135
<210> 294
<211> 134
<212> PRT
<213> 智人(Homo sapiens)
<400> 294
Met His Pro Gly Leu Leu Cys Trp Val Leu Leu Cys Leu Leu Gly Ala
1 5 10 15
Gly Pro Val Asp Ala Gly Val Thr Gln Ser Pro Thr His Leu Ile Lys
20 25 30
Thr Arg Gly Gln Gln Val Thr Leu Arg Cys Ser Pro Ile Ser Gly His
35 40 45
Lys Ser Val Ser Trp Tyr Gln Gln Val Leu Gly Gln Gly Pro Gln Phe
50 55 60
Ile Phe Gln Tyr Tyr Glu Lys Glu Glu Arg Gly Arg Gly Asn Phe Pro
65 70 75 80
Asp Arg Phe Ser Ala Arg Gln Phe Pro Asn Tyr Ser Ser Glu Leu Asn
85 90 95
Val Asn Ala Leu Leu Leu Gly Asp Ser Ala Leu Tyr Leu Cys Ala Ser
100 105 110
Ser Gly Gly Arg Thr Ser Gly Ala Tyr Glu Gln Phe Phe Gly Pro Gly
115 120 125
Thr Arg Leu Thr Val Leu
130
<210> 295
<211> 272
<212> PRT
<213> 智人(Homo sapiens)
<400> 295
Met Ala Gly Ile Arg Ala Leu Phe Met Tyr Leu Trp Leu Gln Leu Asp
1 5 10 15
Trp Val Ser Arg Gly Glu Ser Val Gly Leu His Leu Pro Thr Leu Ser
20 25 30
Val Gln Glu Gly Asp Asn Ser Ile Ile Asn Cys Ala Tyr Ser Asn Ser
35 40 45
Ala Ser Asp Tyr Phe Ile Trp Tyr Lys Gln Glu Ser Gly Lys Gly Pro
50 55 60
Gln Phe Ile Ile Asp Ile Arg Ser Asn Met Asp Lys Arg Gln Gly Gln
65 70 75 80
Arg Val Thr Val Leu Leu Asn Lys Thr Val Lys His Leu Ser Leu Gln
85 90 95
Ile Ala Ala Thr Gln Pro Gly Asp Ser Ala Val Tyr Phe Cys Ala Glu
100 105 110
Pro Val Gly Gly Leu Asn Ser Gly Tyr Ala Leu Asn Phe Gly Lys Gly
115 120 125
Thr Ser Leu Leu Val Thr Pro Asn Ile Gln Asn Pro Glu Pro Ala Val
130 135 140
Tyr Gln Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe
145 150 155 160
Thr Asp Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly
165 170 175
Thr Phe Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser
180 185 190
Lys Ser Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys
195 200 205
Gln Asp Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val
210 215 220
Pro Cys Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn
225 230 235 240
Leu Asn Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu
245 250 255
Lys Val Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser
260 265 270
<210> 296
<211> 307
<212> PRT
<213> 智人(Homo sapiens)
<400> 296
Met His Pro Gly Leu Leu Cys Trp Val Leu Leu Cys Leu Leu Gly Ala
1 5 10 15
Gly Pro Val Asp Ala Gly Val Thr Gln Ser Pro Thr His Leu Ile Lys
20 25 30
Thr Arg Gly Gln Gln Val Thr Leu Arg Cys Ser Pro Ile Ser Gly His
35 40 45
Lys Ser Val Ser Trp Tyr Gln Gln Val Leu Gly Gln Gly Pro Gln Phe
50 55 60
Ile Phe Gln Tyr Tyr Glu Lys Glu Glu Arg Gly Arg Gly Asn Phe Pro
65 70 75 80
Asp Arg Phe Ser Ala Arg Gln Phe Pro Asn Tyr Ser Ser Glu Leu Asn
85 90 95
Val Asn Ala Leu Leu Leu Gly Asp Ser Ala Leu Tyr Leu Cys Ala Ser
100 105 110
Ser Gly Gly Arg Thr Ser Gly Ala Tyr Glu Gln Phe Phe Gly Pro Gly
115 120 125
Thr Arg Leu Thr Val Leu Glu Asp Leu Arg Asn Val Thr Pro Pro Lys
130 135 140
Val Ser Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys
145 150 155 160
Ala Thr Leu Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu
165 170 175
Leu Ser Trp Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr
180 185 190
Asp Pro Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser
195 200 205
Arg Leu Arg Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe
210 215 220
Arg Cys Gln Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro
225 230 235 240
Glu Gly Ser Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp
245 250 255
Gly Arg Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val
260 265 270
Leu Ser Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu
275 280 285
Tyr Ala Val Leu Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg
290 295 300
Lys Asn Ser
305
<210> 297
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 297
Val Ser Gly Leu Arg Gly
1 5
<210> 298
<211> 7
<212> PRT
<213> 智人(Homo sapiens)
<400> 298
Leu Tyr Ser Ala Gly Glu Glu
1 5
<210> 299
<211> 16
<212> PRT
<213> 智人(Homo sapiens)
<400> 299
Cys Ala Val Thr Ala His Arg Gly Ser Thr Leu Gly Arg Leu Tyr Phe
1 5 10 15
<210> 300
<211> 5
<212> PRT
<213> 智人(Homo sapiens)
<400> 300
Ser Gly His Asp Thr
1 5
<210> 301
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 301
Tyr Tyr Glu Glu Glu Glu
1 5
<210> 302
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 302
Cys Ala Ser Ser Arg Arg Gly Gly Ala Tyr Asn Glu Gln Phe Phe
1 5 10 15
<210> 303
<211> 134
<212> PRT
<213> 智人(Homo sapiens)
<400> 303
Met Ala Lys Met Leu Glu Cys Ala Phe Ile Val Leu Trp Leu Gln Leu
1 5 10 15
Gly Trp Leu Ser Gly Glu Asp Gln Val Thr Gln Ser Pro Glu Ala Leu
20 25 30
Arg Leu Gln Glu Gly Glu Ser Ser Ser Leu Asn Cys Ser Tyr Thr Val
35 40 45
Ser Gly Leu Arg Gly Leu Phe Trp Tyr Arg Gln Asp Pro Gly Lys Gly
50 55 60
Pro Glu Phe Leu Phe Thr Leu Tyr Ser Ala Gly Glu Glu Lys Glu Lys
65 70 75 80
Glu Arg Leu Lys Ala Thr Leu Thr Lys Lys Glu Ser Phe Leu His Ile
85 90 95
Thr Ala Pro Lys Pro Glu Asp Ser Ala Thr Tyr Leu Cys Ala Val Thr
100 105 110
Ala His Arg Gly Ser Thr Leu Gly Arg Leu Tyr Phe Gly Arg Gly Thr
115 120 125
Gln Leu Thr Val Trp Pro
130
<210> 304
<211> 133
<212> PRT
<213> 智人(Homo sapiens)
<400> 304
Met His Pro Gly Leu Leu Cys Trp Ala Leu Leu Cys Leu Leu Gly Ala
1 5 10 15
Gly Leu Val Asp Ala Gly Val Thr Gln Ser Pro Thr His Leu Ile Lys
20 25 30
Thr Arg Gly Gln Gln Val Thr Leu Arg Cys Ser Pro Lys Ser Gly His
35 40 45
Asp Thr Val Ser Trp Tyr Gln Gln Ala Leu Gly Gln Gly Pro Gln Phe
50 55 60
Ile Phe Gln Tyr Tyr Glu Glu Glu Glu Arg Gln Arg Gly Asn Phe Pro
65 70 75 80
Asp Arg Phe Ser Gly His Gln Phe Pro Asn Tyr Ser Ser Glu Leu Asn
85 90 95
Val Asn Ala Leu Leu Leu Gly Asp Ser Ala Leu Tyr Leu Cys Ala Ser
100 105 110
Ser Arg Arg Gly Gly Ala Tyr Asn Glu Gln Phe Phe Gly Pro Gly Thr
115 120 125
Arg Leu Thr Val Leu
130
<210> 305
<211> 271
<212> PRT
<213> 智人(Homo sapiens)
<400> 305
Met Ala Lys Met Leu Glu Cys Ala Phe Ile Val Leu Trp Leu Gln Leu
1 5 10 15
Gly Trp Leu Ser Gly Glu Asp Gln Val Thr Gln Ser Pro Glu Ala Leu
20 25 30
Arg Leu Gln Glu Gly Glu Ser Ser Ser Leu Asn Cys Ser Tyr Thr Val
35 40 45
Ser Gly Leu Arg Gly Leu Phe Trp Tyr Arg Gln Asp Pro Gly Lys Gly
50 55 60
Pro Glu Phe Leu Phe Thr Leu Tyr Ser Ala Gly Glu Glu Lys Glu Lys
65 70 75 80
Glu Arg Leu Lys Ala Thr Leu Thr Lys Lys Glu Ser Phe Leu His Ile
85 90 95
Thr Ala Pro Lys Pro Glu Asp Ser Ala Thr Tyr Leu Cys Ala Val Thr
100 105 110
Ala His Arg Gly Ser Thr Leu Gly Arg Leu Tyr Phe Gly Arg Gly Thr
115 120 125
Gln Leu Thr Val Trp Pro Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr
130 135 140
Gln Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr
145 150 155 160
Asp Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr
165 170 175
Phe Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys
180 185 190
Ser Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln
195 200 205
Asp Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro
210 215 220
Cys Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu
225 230 235 240
Asn Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys
245 250 255
Val Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser
260 265 270
<210> 306
<211> 306
<212> PRT
<213> 智人(Homo sapiens)
<400> 306
Met His Pro Gly Leu Leu Cys Trp Ala Leu Leu Cys Leu Leu Gly Ala
1 5 10 15
Gly Leu Val Asp Ala Gly Val Thr Gln Ser Pro Thr His Leu Ile Lys
20 25 30
Thr Arg Gly Gln Gln Val Thr Leu Arg Cys Ser Pro Lys Ser Gly His
35 40 45
Asp Thr Val Ser Trp Tyr Gln Gln Ala Leu Gly Gln Gly Pro Gln Phe
50 55 60
Ile Phe Gln Tyr Tyr Glu Glu Glu Glu Arg Gln Arg Gly Asn Phe Pro
65 70 75 80
Asp Arg Phe Ser Gly His Gln Phe Pro Asn Tyr Ser Ser Glu Leu Asn
85 90 95
Val Asn Ala Leu Leu Leu Gly Asp Ser Ala Leu Tyr Leu Cys Ala Ser
100 105 110
Ser Arg Arg Gly Gly Ala Tyr Asn Glu Gln Phe Phe Gly Pro Gly Thr
115 120 125
Arg Leu Thr Val Leu Glu Asp Leu Arg Asn Val Thr Pro Pro Lys Val
130 135 140
Ser Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys Ala
145 150 155 160
Thr Leu Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu Leu
165 170 175
Ser Trp Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr Asp
180 185 190
Pro Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser Arg
195 200 205
Leu Arg Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe Arg
210 215 220
Cys Gln Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro Glu
225 230 235 240
Gly Ser Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp Gly
245 250 255
Arg Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val Leu
260 265 270
Ser Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu Tyr
275 280 285
Ala Val Leu Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg Lys
290 295 300
Asn Ser
305
<210> 307
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 307
Ser Ser Asn Phe Tyr Ala
1 5
<210> 308
<211> 7
<212> PRT
<213> 智人(Homo sapiens)
<400> 308
Met Thr Leu Asn Gly Asp Glu
1 5
<210> 309
<211> 13
<212> PRT
<213> 智人(Homo sapiens)
<400> 309
Cys Ala Ser Val Gly Gly Gly Ala Asp Gly Leu Thr Phe
1 5 10
<210> 310
<211> 5
<212> PRT
<213> 智人(Homo sapiens)
<400> 310
Ser Gly His Thr Ala
1 5
<210> 311
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 311
Phe Gln Gly Asn Ser Ala
1 5
<210> 312
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 312
Cys Ala Ser Thr Trp Asp Arg Gly Ser Tyr Asn Glu Gln Phe Phe
1 5 10 15
<210> 313
<211> 134
<212> PRT
<213> 智人(Homo sapiens)
<400> 313
Met Ala Lys Asn Pro Leu Ala Ala Pro Leu Leu Ile Leu Trp Phe His
1 5 10 15
Leu Asp Cys Val Ser Ser Ile Leu Asn Val Glu Gln Ser Pro Gln Ser
20 25 30
Leu His Val Gln Glu Gly Asp Ser Thr Asn Phe Thr Cys Ser Phe Pro
35 40 45
Ser Ser Asn Phe Tyr Ala Leu His Trp Tyr Arg Trp Glu Thr Ala Lys
50 55 60
Ser Pro Glu Ala Leu Phe Val Met Thr Leu Asn Gly Asp Glu Lys Lys
65 70 75 80
Lys Gly Arg Ile Ser Ala Thr Leu Asn Thr Lys Glu Gly Tyr Ser Tyr
85 90 95
Leu Tyr Ile Lys Gly Ser Gln Pro Glu Asp Ser Ala Thr Tyr Leu Cys
100 105 110
Ala Ser Val Gly Gly Gly Ala Asp Gly Leu Thr Phe Gly Lys Gly Thr
115 120 125
His Leu Ile Ile Gln Pro
130
<210> 314
<211> 134
<212> PRT
<213> 智人(Homo sapiens)
<400> 314
Met His Thr Arg Leu Leu Phe Trp Val Ala Phe Cys Leu Leu Gly Ala
1 5 10 15
Asp His Thr Gly Ala Gly Val Ser Gln Ser Pro Ser Asn Lys Val Thr
20 25 30
Glu Lys Gly Lys Asp Val Glu Leu Arg Cys Asp Pro Ile Ser Gly His
35 40 45
Thr Ala Leu Tyr Trp Tyr Arg Gln Ser Leu Gly Gln Gly Leu Glu Phe
50 55 60
Leu Ile Tyr Phe Gln Gly Asn Ser Ala Pro Asp Lys Ser Gly Leu Pro
65 70 75 80
Ser Asp Arg Phe Ser Ala Glu Arg Thr Gly Gly Ser Val Ser Thr Leu
85 90 95
Thr Ile Gln Arg Thr Gln Gln Glu Asp Ser Ala Val Tyr Leu Cys Ala
100 105 110
Ser Thr Trp Asp Arg Gly Ser Tyr Asn Glu Gln Phe Phe Gly Pro Gly
115 120 125
Thr Arg Leu Thr Val Leu
130
<210> 315
<211> 271
<212> PRT
<213> 智人(Homo sapiens)
<400> 315
Met Ala Lys Asn Pro Leu Ala Ala Pro Leu Leu Ile Leu Trp Phe His
1 5 10 15
Leu Asp Cys Val Ser Ser Ile Leu Asn Val Glu Gln Ser Pro Gln Ser
20 25 30
Leu His Val Gln Glu Gly Asp Ser Thr Asn Phe Thr Cys Ser Phe Pro
35 40 45
Ser Ser Asn Phe Tyr Ala Leu His Trp Tyr Arg Trp Glu Thr Ala Lys
50 55 60
Ser Pro Glu Ala Leu Phe Val Met Thr Leu Asn Gly Asp Glu Lys Lys
65 70 75 80
Lys Gly Arg Ile Ser Ala Thr Leu Asn Thr Lys Glu Gly Tyr Ser Tyr
85 90 95
Leu Tyr Ile Lys Gly Ser Gln Pro Glu Asp Ser Ala Thr Tyr Leu Cys
100 105 110
Ala Ser Val Gly Gly Gly Ala Asp Gly Leu Thr Phe Gly Lys Gly Thr
115 120 125
His Leu Ile Ile Gln Pro Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr
130 135 140
Gln Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr
145 150 155 160
Asp Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr
165 170 175
Phe Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys
180 185 190
Ser Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln
195 200 205
Asp Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro
210 215 220
Cys Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu
225 230 235 240
Asn Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys
245 250 255
Val Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser
260 265 270
<210> 316
<211> 307
<212> PRT
<213> 智人(Homo sapiens)
<400> 316
Met His Thr Arg Leu Leu Phe Trp Val Ala Phe Cys Leu Leu Gly Ala
1 5 10 15
Asp His Thr Gly Ala Gly Val Ser Gln Ser Pro Ser Asn Lys Val Thr
20 25 30
Glu Lys Gly Lys Asp Val Glu Leu Arg Cys Asp Pro Ile Ser Gly His
35 40 45
Thr Ala Leu Tyr Trp Tyr Arg Gln Ser Leu Gly Gln Gly Leu Glu Phe
50 55 60
Leu Ile Tyr Phe Gln Gly Asn Ser Ala Pro Asp Lys Ser Gly Leu Pro
65 70 75 80
Ser Asp Arg Phe Ser Ala Glu Arg Thr Gly Gly Ser Val Ser Thr Leu
85 90 95
Thr Ile Gln Arg Thr Gln Gln Glu Asp Ser Ala Val Tyr Leu Cys Ala
100 105 110
Ser Thr Trp Asp Arg Gly Ser Tyr Asn Glu Gln Phe Phe Gly Pro Gly
115 120 125
Thr Arg Leu Thr Val Leu Glu Asp Leu Arg Asn Val Thr Pro Pro Lys
130 135 140
Val Ser Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys
145 150 155 160
Ala Thr Leu Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu
165 170 175
Leu Ser Trp Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr
180 185 190
Asp Pro Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser
195 200 205
Arg Leu Arg Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe
210 215 220
Arg Cys Gln Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro
225 230 235 240
Glu Gly Ser Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp
245 250 255
Gly Arg Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val
260 265 270
Leu Ser Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu
275 280 285
Tyr Ala Val Leu Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg
290 295 300
Lys Asn Ser
305
<210> 317
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 317
Asn Ser Met Phe Asp Tyr
1 5
<210> 318
<211> 7
<212> PRT
<213> 智人(Homo sapiens)
<400> 318
Ile Ser Ser Ile Lys Asp Lys
1 5
<210> 319
<211> 11
<212> PRT
<213> 智人(Homo sapiens)
<400> 319
Cys Ala Ala Asn Thr Gly Asn Gln Phe Tyr Phe
1 5 10
<210> 320
<211> 5
<212> PRT
<213> 智人(Homo sapiens)
<400> 320
Ser Gly His Ala Thr
1 5
<210> 321
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 321
Phe Gln Asn Asn Gly Val
1 5
<210> 322
<211> 16
<212> PRT
<213> 智人(Homo sapiens)
<400> 322
Cys Ala Ser Ser His Leu Ala Gly Glu Phe Tyr Asn Glu Gln Phe Phe
1 5 10 15
<210> 323
<211> 136
<212> PRT
<213> 智人(Homo sapiens)
<400> 323
Met Ala Met Leu Leu Gly Ala Ser Val Leu Ile Leu Trp Leu Gln Pro
1 5 10 15
Asp Trp Val Asn Ser Gln Gln Lys Asn Asp Asp Gln Gln Val Lys Gln
20 25 30
Asn Ser Pro Ser Leu Ser Val Gln Glu Gly Arg Ile Ser Ile Leu Asn
35 40 45
Cys Asp Tyr Thr Asn Ser Met Phe Asp Tyr Phe Leu Trp Tyr Lys Lys
50 55 60
Tyr Pro Ala Glu Gly Pro Thr Phe Leu Ile Ser Ile Ser Ser Ile Lys
65 70 75 80
Asp Lys Asn Glu Asp Gly Arg Phe Thr Val Phe Leu Asn Lys Ser Ala
85 90 95
Lys His Leu Ser Leu His Ile Val Pro Ser Gln Pro Gly Asp Ser Ala
100 105 110
Val Tyr Phe Cys Ala Ala Asn Thr Gly Asn Gln Phe Tyr Phe Gly Thr
115 120 125
Gly Thr Ser Leu Thr Val Ile Pro
130 135
<210> 324
<211> 135
<212> PRT
<213> 智人(Homo sapiens)
<400> 324
Met His Thr Arg Leu Leu Cys Trp Ala Ala Leu Cys Leu Leu Gly Ala
1 5 10 15
Glu Leu Thr Glu Ala Gly Val Ala Gln Ser Pro Arg Tyr Lys Ile Ile
20 25 30
Glu Lys Arg Gln Ser Val Ala Phe Trp Cys Asn Pro Ile Ser Gly His
35 40 45
Ala Thr Leu Tyr Trp Tyr Gln Gln Ile Leu Gly Gln Gly Pro Lys Leu
50 55 60
Leu Ile Gln Phe Gln Asn Asn Gly Val Val Asp Asp Ser Gln Leu Pro
65 70 75 80
Lys Asp Arg Phe Ser Ala Glu Arg Leu Lys Gly Val Asp Ser Thr Leu
85 90 95
Lys Ile Gln Pro Ala Lys Leu Glu Asp Ser Ala Val Tyr Leu Cys Ala
100 105 110
Ser Ser His Leu Ala Gly Glu Phe Tyr Asn Glu Gln Phe Phe Gly Pro
115 120 125
Gly Thr Arg Leu Thr Val Leu
130 135
<210> 325
<211> 273
<212> PRT
<213> 智人(Homo sapiens)
<400> 325
Met Ala Met Leu Leu Gly Ala Ser Val Leu Ile Leu Trp Leu Gln Pro
1 5 10 15
Asp Trp Val Asn Ser Gln Gln Lys Asn Asp Asp Gln Gln Val Lys Gln
20 25 30
Asn Ser Pro Ser Leu Ser Val Gln Glu Gly Arg Ile Ser Ile Leu Asn
35 40 45
Cys Asp Tyr Thr Asn Ser Met Phe Asp Tyr Phe Leu Trp Tyr Lys Lys
50 55 60
Tyr Pro Ala Glu Gly Pro Thr Phe Leu Ile Ser Ile Ser Ser Ile Lys
65 70 75 80
Asp Lys Asn Glu Asp Gly Arg Phe Thr Val Phe Leu Asn Lys Ser Ala
85 90 95
Lys His Leu Ser Leu His Ile Val Pro Ser Gln Pro Gly Asp Ser Ala
100 105 110
Val Tyr Phe Cys Ala Ala Asn Thr Gly Asn Gln Phe Tyr Phe Gly Thr
115 120 125
Gly Thr Ser Leu Thr Val Ile Pro Asn Ile Gln Asn Pro Glu Pro Ala
130 135 140
Val Tyr Gln Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu
145 150 155 160
Phe Thr Asp Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser
165 170 175
Gly Thr Phe Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp
180 185 190
Ser Lys Ser Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr
195 200 205
Cys Gln Asp Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp
210 215 220
Val Pro Cys Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met
225 230 235 240
Asn Leu Asn Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu
245 250 255
Leu Lys Val Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser
260 265 270
Ser
<210> 326
<211> 308
<212> PRT
<213> 智人(Homo sapiens)
<400> 326
Met His Thr Arg Leu Leu Cys Trp Ala Ala Leu Cys Leu Leu Gly Ala
1 5 10 15
Glu Leu Thr Glu Ala Gly Val Ala Gln Ser Pro Arg Tyr Lys Ile Ile
20 25 30
Glu Lys Arg Gln Ser Val Ala Phe Trp Cys Asn Pro Ile Ser Gly His
35 40 45
Ala Thr Leu Tyr Trp Tyr Gln Gln Ile Leu Gly Gln Gly Pro Lys Leu
50 55 60
Leu Ile Gln Phe Gln Asn Asn Gly Val Val Asp Asp Ser Gln Leu Pro
65 70 75 80
Lys Asp Arg Phe Ser Ala Glu Arg Leu Lys Gly Val Asp Ser Thr Leu
85 90 95
Lys Ile Gln Pro Ala Lys Leu Glu Asp Ser Ala Val Tyr Leu Cys Ala
100 105 110
Ser Ser His Leu Ala Gly Glu Phe Tyr Asn Glu Gln Phe Phe Gly Pro
115 120 125
Gly Thr Arg Leu Thr Val Leu Glu Asp Leu Arg Asn Val Thr Pro Pro
130 135 140
Lys Val Ser Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln
145 150 155 160
Lys Ala Thr Leu Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val
165 170 175
Glu Leu Ser Trp Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys
180 185 190
Thr Asp Pro Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser
195 200 205
Ser Arg Leu Arg Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn His
210 215 220
Phe Arg Cys Gln Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp
225 230 235 240
Pro Glu Gly Ser Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala
245 250 255
Trp Gly Arg Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly
260 265 270
Val Leu Ser Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr
275 280 285
Leu Tyr Ala Val Leu Val Ser Thr Leu Val Val Met Ala Met Val Lys
290 295 300
Arg Lys Asn Ser
305
<210> 327
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 327
Thr Ser Gly Phe Tyr Gly
1 5
<210> 328
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 328
Asn Ala Leu Asp Gly Leu
1 5
<210> 329
<211> 11
<212> PRT
<213> 智人(Homo sapiens)
<400> 329
Cys Ala Phe Ala Tyr Gly Gln Asn Phe Val Phe
1 5 10
<210> 330
<211> 5
<212> PRT
<213> 智人(Homo sapiens)
<400> 330
Ser Gly Asp Leu Ser
1 5
<210> 331
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 331
Tyr Tyr Asn Gly Glu Glu
1 5
<210> 332
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 332
Cys Ala Ser Ser Pro Leu Gly Asp Ser Gly Asn Thr Ile Tyr Phe
1 5 10 15
<210> 333
<211> 125
<212> PRT
<213> 智人(Homo sapiens)
<400> 333
Met Ala Gly Ala Phe Leu Leu Tyr Val Ser Met Lys Met Gly Gly Thr
1 5 10 15
Ala Gly Gln Ser Leu Glu Gln Pro Ser Glu Val Thr Ala Val Glu Gly
20 25 30
Ala Ile Val Gln Ile Asn Cys Thr Tyr Gln Thr Ser Gly Phe Tyr Gly
35 40 45
Leu Ser Trp Tyr Gln Gln His Asp Gly Gly Ala Pro Thr Phe Leu Ser
50 55 60
Tyr Asn Ala Leu Asp Gly Leu Glu Glu Thr Gly Arg Phe Ser Ser Phe
65 70 75 80
Leu Ser Arg Ser Asp Ser Tyr Gly Tyr Leu Leu Leu Gln Glu Leu Gln
85 90 95
Met Lys Asp Ser Ala Ser Tyr Phe Cys Ala Phe Ala Tyr Gly Gln Asn
100 105 110
Phe Val Phe Gly Pro Gly Thr Arg Leu Ser Val Leu Pro
115 120 125
<210> 334
<211> 133
<212> PRT
<213> 智人(Homo sapiens)
<400> 334
Met His Phe Arg Leu Leu Cys Cys Val Ala Phe Cys Leu Leu Gly Ala
1 5 10 15
Gly Pro Val Asp Ser Gly Val Thr Gln Thr Pro Lys His Leu Ile Thr
20 25 30
Ala Thr Gly Gln Arg Val Thr Leu Arg Cys Ser Pro Arg Ser Gly Asp
35 40 45
Leu Ser Val Tyr Trp Tyr Gln Gln Ser Leu Asp Gln Gly Leu Gln Phe
50 55 60
Leu Ile Gln Tyr Tyr Asn Gly Glu Glu Arg Ala Lys Gly Asn Ile Leu
65 70 75 80
Glu Arg Phe Ser Ala Gln Gln Phe Pro Asp Leu His Ser Glu Leu Asn
85 90 95
Leu Ser Ser Leu Glu Leu Gly Asp Ser Ala Leu Tyr Phe Cys Ala Ser
100 105 110
Ser Pro Leu Gly Asp Ser Gly Asn Thr Ile Tyr Phe Gly Glu Gly Ser
115 120 125
Trp Leu Thr Val Val
130
<210> 335
<211> 262
<212> PRT
<213> 智人(Homo sapiens)
<400> 335
Met Ala Gly Ala Phe Leu Leu Tyr Val Ser Met Lys Met Gly Gly Thr
1 5 10 15
Ala Gly Gln Ser Leu Glu Gln Pro Ser Glu Val Thr Ala Val Glu Gly
20 25 30
Ala Ile Val Gln Ile Asn Cys Thr Tyr Gln Thr Ser Gly Phe Tyr Gly
35 40 45
Leu Ser Trp Tyr Gln Gln His Asp Gly Gly Ala Pro Thr Phe Leu Ser
50 55 60
Tyr Asn Ala Leu Asp Gly Leu Glu Glu Thr Gly Arg Phe Ser Ser Phe
65 70 75 80
Leu Ser Arg Ser Asp Ser Tyr Gly Tyr Leu Leu Leu Gln Glu Leu Gln
85 90 95
Met Lys Asp Ser Ala Ser Tyr Phe Cys Ala Phe Ala Tyr Gly Gln Asn
100 105 110
Phe Val Phe Gly Pro Gly Thr Arg Leu Ser Val Leu Pro Asn Ile Gln
115 120 125
Asn Pro Glu Pro Ala Val Tyr Gln Leu Lys Asp Pro Arg Ser Gln Asp
130 135 140
Ser Thr Leu Cys Leu Phe Thr Asp Phe Asp Ser Gln Ile Asn Val Pro
145 150 155 160
Lys Thr Met Glu Ser Gly Thr Phe Ile Thr Asp Lys Cys Val Leu Asp
165 170 175
Met Lys Ala Met Asp Ser Lys Ser Asn Gly Ala Ile Ala Trp Ser Asn
180 185 190
Gln Thr Ser Phe Thr Cys Gln Asp Ile Phe Lys Glu Thr Asn Ala Thr
195 200 205
Tyr Pro Ser Ser Asp Val Pro Cys Asp Ala Thr Leu Thr Glu Lys Ser
210 215 220
Phe Glu Thr Asp Met Asn Leu Asn Phe Gln Asn Leu Leu Val Ile Val
225 230 235 240
Leu Arg Ile Leu Leu Leu Lys Val Ala Gly Phe Asn Leu Leu Met Thr
245 250 255
Leu Arg Leu Trp Ser Ser
260
<210> 336
<211> 306
<212> PRT
<213> 智人(Homo sapiens)
<400> 336
Met His Phe Arg Leu Leu Cys Cys Val Ala Phe Cys Leu Leu Gly Ala
1 5 10 15
Gly Pro Val Asp Ser Gly Val Thr Gln Thr Pro Lys His Leu Ile Thr
20 25 30
Ala Thr Gly Gln Arg Val Thr Leu Arg Cys Ser Pro Arg Ser Gly Asp
35 40 45
Leu Ser Val Tyr Trp Tyr Gln Gln Ser Leu Asp Gln Gly Leu Gln Phe
50 55 60
Leu Ile Gln Tyr Tyr Asn Gly Glu Glu Arg Ala Lys Gly Asn Ile Leu
65 70 75 80
Glu Arg Phe Ser Ala Gln Gln Phe Pro Asp Leu His Ser Glu Leu Asn
85 90 95
Leu Ser Ser Leu Glu Leu Gly Asp Ser Ala Leu Tyr Phe Cys Ala Ser
100 105 110
Ser Pro Leu Gly Asp Ser Gly Asn Thr Ile Tyr Phe Gly Glu Gly Ser
115 120 125
Trp Leu Thr Val Val Glu Asp Leu Arg Asn Val Thr Pro Pro Lys Val
130 135 140
Ser Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys Ala
145 150 155 160
Thr Leu Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu Leu
165 170 175
Ser Trp Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr Asp
180 185 190
Pro Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser Arg
195 200 205
Leu Arg Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe Arg
210 215 220
Cys Gln Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro Glu
225 230 235 240
Gly Ser Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp Gly
245 250 255
Arg Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val Leu
260 265 270
Ser Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu Tyr
275 280 285
Ala Val Leu Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg Lys
290 295 300
Asn Ser
305
<210> 337
<211> 5
<212> PRT
<213> 智人(Homo sapiens)
<400> 337
Thr Ser Ile Asn Asn
1 5
<210> 338
<211> 7
<212> PRT
<213> 智人(Homo sapiens)
<400> 338
Ile Arg Ser Asn Glu Arg Glu
1 5
<210> 339
<211> 12
<212> PRT
<213> 智人(Homo sapiens)
<400> 339
Cys Ala Thr Asp Ala Trp Asn Asn Asp Met Arg Phe
1 5 10
<210> 340
<211> 5
<212> PRT
<213> 智人(Homo sapiens)
<400> 340
Met Asn His Asn Ser
1 5
<210> 341
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 341
Ser Ala Ser Glu Gly Thr
1 5
<210> 342
<211> 14
<212> PRT
<213> 智人(Homo sapiens)
<400> 342
Cys Ala Ser Ser Glu Ser Gln Gly Asn Thr Glu Ala Phe Phe
1 5 10
<210> 343
<211> 130
<212> PRT
<213> 智人(Homo sapiens)
<400> 343
Met Ala Thr Leu Leu Gly Val Ser Leu Val Ile Leu Trp Leu Gln Leu
1 5 10 15
Ala Arg Val Asn Ser Gln Gln Gly Glu Glu Asp Pro Gln Ala Leu Ser
20 25 30
Ile Gln Glu Gly Glu Asn Ala Thr Met Asn Cys Ser Tyr Lys Thr Ser
35 40 45
Ile Asn Asn Leu Gln Trp Tyr Arg Gln Asn Ser Gly Arg Gly Leu Val
50 55 60
His Leu Ile Leu Ile Arg Ser Asn Glu Arg Glu Lys His Ser Gly Arg
65 70 75 80
Leu Arg Val Thr Leu Asp Thr Ser Lys Lys Ser Ser Ser Leu Leu Ile
85 90 95
Thr Ala Ser Arg Ala Ala Asp Thr Ala Ser Tyr Phe Cys Ala Thr Asp
100 105 110
Ala Trp Asn Asn Asp Met Arg Phe Gly Ala Gly Thr Arg Leu Thr Val
115 120 125
Lys Pro
130
<210> 344
<211> 132
<212> PRT
<213> 智人(Homo sapiens)
<400> 344
Met His Ile Gly Leu Leu Cys Cys Val Ala Phe Ser Leu Leu Trp Ala
1 5 10 15
Ser Pro Val Asn Ala Gly Val Thr Gln Thr Pro Lys Phe Gln Val Leu
20 25 30
Lys Thr Gly Gln Ser Met Thr Leu Gln Cys Ala Gln Asp Met Asn His
35 40 45
Asn Ser Met Tyr Trp Tyr Arg Gln Asp Pro Gly Met Gly Leu Arg Leu
50 55 60
Ile Tyr Tyr Ser Ala Ser Glu Gly Thr Thr Asp Lys Gly Glu Val Pro
65 70 75 80
Asn Gly Tyr Asn Val Ser Arg Leu Asn Lys Arg Glu Phe Ser Leu Arg
85 90 95
Leu Glu Ser Ala Ala Pro Ser Gln Thr Ser Val Tyr Phe Cys Ala Ser
100 105 110
Ser Glu Ser Gln Gly Asn Thr Glu Ala Phe Phe Gly Gln Gly Thr Arg
115 120 125
Leu Thr Val Val
130
<210> 345
<211> 267
<212> PRT
<213> 智人(Homo sapiens)
<400> 345
Met Ala Thr Leu Leu Gly Val Ser Leu Val Ile Leu Trp Leu Gln Leu
1 5 10 15
Ala Arg Val Asn Ser Gln Gln Gly Glu Glu Asp Pro Gln Ala Leu Ser
20 25 30
Ile Gln Glu Gly Glu Asn Ala Thr Met Asn Cys Ser Tyr Lys Thr Ser
35 40 45
Ile Asn Asn Leu Gln Trp Tyr Arg Gln Asn Ser Gly Arg Gly Leu Val
50 55 60
His Leu Ile Leu Ile Arg Ser Asn Glu Arg Glu Lys His Ser Gly Arg
65 70 75 80
Leu Arg Val Thr Leu Asp Thr Ser Lys Lys Ser Ser Ser Leu Leu Ile
85 90 95
Thr Ala Ser Arg Ala Ala Asp Thr Ala Ser Tyr Phe Cys Ala Thr Asp
100 105 110
Ala Trp Asn Asn Asp Met Arg Phe Gly Ala Gly Thr Arg Leu Thr Val
115 120 125
Lys Pro Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr Gln Leu Lys Asp
130 135 140
Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr Asp Phe Asp Ser
145 150 155 160
Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr Phe Ile Thr Asp
165 170 175
Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys Ser Asn Gly Ala
180 185 190
Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln Asp Ile Phe Lys
195 200 205
Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro Cys Asp Ala Thr
210 215 220
Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu Asn Phe Gln Asn
225 230 235 240
Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys Val Ala Gly Phe
245 250 255
Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser
260 265
<210> 346
<211> 305
<212> PRT
<213> 智人(Homo sapiens)
<400> 346
Met His Ile Gly Leu Leu Cys Cys Val Ala Phe Ser Leu Leu Trp Ala
1 5 10 15
Ser Pro Val Asn Ala Gly Val Thr Gln Thr Pro Lys Phe Gln Val Leu
20 25 30
Lys Thr Gly Gln Ser Met Thr Leu Gln Cys Ala Gln Asp Met Asn His
35 40 45
Asn Ser Met Tyr Trp Tyr Arg Gln Asp Pro Gly Met Gly Leu Arg Leu
50 55 60
Ile Tyr Tyr Ser Ala Ser Glu Gly Thr Thr Asp Lys Gly Glu Val Pro
65 70 75 80
Asn Gly Tyr Asn Val Ser Arg Leu Asn Lys Arg Glu Phe Ser Leu Arg
85 90 95
Leu Glu Ser Ala Ala Pro Ser Gln Thr Ser Val Tyr Phe Cys Ala Ser
100 105 110
Ser Glu Ser Gln Gly Asn Thr Glu Ala Phe Phe Gly Gln Gly Thr Arg
115 120 125
Leu Thr Val Val Glu Asp Leu Arg Asn Val Thr Pro Pro Lys Val Ser
130 135 140
Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys Ala Thr
145 150 155 160
Leu Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu Leu Ser
165 170 175
Trp Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr Asp Pro
180 185 190
Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser Arg Leu
195 200 205
Arg Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe Arg Cys
210 215 220
Gln Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro Glu Gly
225 230 235 240
Ser Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp Gly Arg
245 250 255
Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val Leu Ser
260 265 270
Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu Tyr Ala
275 280 285
Val Leu Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg Lys Asn
290 295 300
Ser
305
<210> 347
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 347
Val Ser Pro Phe Ser Asn
1 5
<210> 348
<211> 7
<212> PRT
<213> 智人(Homo sapiens)
<400> 348
Met Thr Phe Ser Glu Asn Thr
1 5
<210> 349
<211> 10
<212> PRT
<213> 智人(Homo sapiens)
<400> 349
Cys Val Val Ser Ser Tyr Lys Ile Ile Phe
1 5 10
<210> 350
<211> 5
<212> PRT
<213> 智人(Homo sapiens)
<400> 350
Ser Gly His Thr Ala
1 5
<210> 351
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 351
Phe Gln Gly Asn Ser Ala
1 5
<210> 352
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 352
Cys Ala Ser Ser Pro Ile Gln Gly Glu Asn Ser Pro Leu His Phe
1 5 10 15
<210> 353
<211> 130
<212> PRT
<213> 智人(Homo sapiens)
<400> 353
Met Ala Lys His Leu Thr Thr Phe Leu Val Ile Leu Trp Leu Tyr Phe
1 5 10 15
Tyr Arg Gly Asn Gly Lys Asn Gln Val Glu Gln Ser Pro Gln Ser Leu
20 25 30
Ile Ile Leu Glu Gly Lys Asn Cys Thr Leu Gln Cys Asn Tyr Thr Val
35 40 45
Ser Pro Phe Ser Asn Leu Arg Trp Tyr Lys Gln Asp Thr Gly Arg Gly
50 55 60
Pro Val Ser Leu Thr Ile Met Thr Phe Ser Glu Asn Thr Lys Ser Asn
65 70 75 80
Gly Arg Tyr Thr Ala Thr Leu Asp Ala Asp Thr Lys Gln Ser Ser Leu
85 90 95
His Ile Thr Ala Ser Gln Leu Ser Asp Ser Ala Ser Tyr Ile Cys Val
100 105 110
Val Ser Ser Tyr Lys Ile Ile Phe Gly Thr Gly Thr Arg Leu His Val
115 120 125
Phe Pro
130
<210> 354
<211> 134
<212> PRT
<213> 智人(Homo sapiens)
<400> 354
Met His Thr Arg Leu Leu Phe Trp Val Ala Phe Cys Leu Leu Gly Ala
1 5 10 15
Tyr His Thr Gly Ala Gly Val Ser Gln Ser Pro Ser Asn Lys Val Thr
20 25 30
Glu Lys Gly Lys Asp Val Glu Leu Arg Cys Asp Pro Ile Ser Gly His
35 40 45
Thr Ala Leu Tyr Trp Tyr Arg Gln Arg Leu Gly Gln Gly Leu Glu Phe
50 55 60
Leu Ile Tyr Phe Gln Gly Asn Ser Ala Pro Asp Lys Ser Gly Leu Pro
65 70 75 80
Ser Asp Arg Phe Ser Ala Glu Arg Thr Gly Glu Ser Val Ser Thr Leu
85 90 95
Thr Ile Gln Arg Thr Gln Gln Glu Asp Ser Ala Val Tyr Leu Cys Ala
100 105 110
Ser Ser Pro Ile Gln Gly Glu Asn Ser Pro Leu His Phe Gly Asn Gly
115 120 125
Thr Arg Leu Thr Val Thr
130
<210> 355
<211> 267
<212> PRT
<213> 智人(Homo sapiens)
<400> 355
Met Ala Lys His Leu Thr Thr Phe Leu Val Ile Leu Trp Leu Tyr Phe
1 5 10 15
Tyr Arg Gly Asn Gly Lys Asn Gln Val Glu Gln Ser Pro Gln Ser Leu
20 25 30
Ile Ile Leu Glu Gly Lys Asn Cys Thr Leu Gln Cys Asn Tyr Thr Val
35 40 45
Ser Pro Phe Ser Asn Leu Arg Trp Tyr Lys Gln Asp Thr Gly Arg Gly
50 55 60
Pro Val Ser Leu Thr Ile Met Thr Phe Ser Glu Asn Thr Lys Ser Asn
65 70 75 80
Gly Arg Tyr Thr Ala Thr Leu Asp Ala Asp Thr Lys Gln Ser Ser Leu
85 90 95
His Ile Thr Ala Ser Gln Leu Ser Asp Ser Ala Ser Tyr Ile Cys Val
100 105 110
Val Ser Ser Tyr Lys Ile Ile Phe Gly Thr Gly Thr Arg Leu His Val
115 120 125
Phe Pro Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr Gln Leu Lys Asp
130 135 140
Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr Asp Phe Asp Ser
145 150 155 160
Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr Phe Ile Thr Asp
165 170 175
Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys Ser Asn Gly Ala
180 185 190
Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln Asp Ile Phe Lys
195 200 205
Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro Cys Asp Ala Thr
210 215 220
Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu Asn Phe Gln Asn
225 230 235 240
Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys Val Ala Gly Phe
245 250 255
Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser
260 265
<210> 356
<211> 307
<212> PRT
<213> 智人(Homo sapiens)
<400> 356
Met His Thr Arg Leu Leu Phe Trp Val Ala Phe Cys Leu Leu Gly Ala
1 5 10 15
Tyr His Thr Gly Ala Gly Val Ser Gln Ser Pro Ser Asn Lys Val Thr
20 25 30
Glu Lys Gly Lys Asp Val Glu Leu Arg Cys Asp Pro Ile Ser Gly His
35 40 45
Thr Ala Leu Tyr Trp Tyr Arg Gln Arg Leu Gly Gln Gly Leu Glu Phe
50 55 60
Leu Ile Tyr Phe Gln Gly Asn Ser Ala Pro Asp Lys Ser Gly Leu Pro
65 70 75 80
Ser Asp Arg Phe Ser Ala Glu Arg Thr Gly Glu Ser Val Ser Thr Leu
85 90 95
Thr Ile Gln Arg Thr Gln Gln Glu Asp Ser Ala Val Tyr Leu Cys Ala
100 105 110
Ser Ser Pro Ile Gln Gly Glu Asn Ser Pro Leu His Phe Gly Asn Gly
115 120 125
Thr Arg Leu Thr Val Thr Glu Asp Leu Arg Asn Val Thr Pro Pro Lys
130 135 140
Val Ser Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys
145 150 155 160
Ala Thr Leu Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu
165 170 175
Leu Ser Trp Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr
180 185 190
Asp Pro Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser
195 200 205
Arg Leu Arg Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe
210 215 220
Arg Cys Gln Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro
225 230 235 240
Glu Gly Ser Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp
245 250 255
Gly Arg Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val
260 265 270
Leu Ser Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu
275 280 285
Tyr Ala Val Leu Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg
290 295 300
Lys Asn Ser
305
<210> 357
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 357
Val Ser Pro Phe Ser Asn
1 5
<210> 358
<211> 7
<212> PRT
<213> 智人(Homo sapiens)
<400> 358
Met Thr Phe Ser Glu Asn Thr
1 5
<210> 359
<211> 11
<212> PRT
<213> 智人(Homo sapiens)
<400> 359
Ile Cys Val Val Ser Ser Tyr Lys Leu Ile Phe
1 5 10
<210> 360
<211> 5
<212> PRT
<213> 智人(Homo sapiens)
<400> 360
Ser Gly His Thr Ala
1 5
<210> 361
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 361
Phe Gln Gly Asn Ser Ala
1 5
<210> 362
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 362
Cys Ala Ser Ser Pro Ile Gln Gly Glu Asn Ser Pro Leu His Phe
1 5 10 15
<210> 363
<211> 130
<212> PRT
<213> 智人(Homo sapiens)
<400> 363
Met Ala Lys His Leu Thr Thr Phe Leu Val Ile Leu Trp Leu Tyr Phe
1 5 10 15
Tyr Arg Gly Asn Gly Lys Asn Gln Val Glu Gln Ser Pro Gln Ser Leu
20 25 30
Ile Ile Leu Glu Gly Lys Asn Cys Thr Leu Gln Cys Asn Tyr Thr Val
35 40 45
Ser Pro Phe Ser Asn Leu Arg Trp Tyr Lys Gln Asp Thr Gly Arg Gly
50 55 60
Pro Val Ser Leu Thr Ile Met Thr Phe Ser Glu Asn Thr Lys Ser Asn
65 70 75 80
Gly Arg Tyr Thr Ala Thr Leu Asp Ala Asp Thr Lys Gln Ser Ser Leu
85 90 95
His Ile Thr Ala Ser Gln Leu Ser Asp Ser Ala Ser Tyr Ile Cys Val
100 105 110
Val Ser Ser Tyr Lys Leu Ile Phe Gly Thr Gly Thr Arg Leu Gln Val
115 120 125
Phe Pro
130
<210> 364
<211> 134
<212> PRT
<213> 智人(Homo sapiens)
<400> 364
Met His Thr Arg Leu Leu Phe Trp Val Ala Phe Cys Leu Leu Gly Ala
1 5 10 15
Tyr His Thr Gly Ala Gly Val Ser Gln Ser Pro Ser Asn Lys Val Thr
20 25 30
Glu Lys Gly Lys Asp Val Glu Leu Arg Cys Asp Pro Ile Ser Gly His
35 40 45
Thr Ala Leu Tyr Trp Tyr Arg Gln Arg Leu Gly Gln Gly Leu Glu Phe
50 55 60
Leu Ile Tyr Phe Gln Gly Asn Ser Ala Pro Asp Lys Ser Gly Leu Pro
65 70 75 80
Ser Asp Arg Phe Ser Ala Glu Arg Thr Gly Glu Ser Val Ser Thr Leu
85 90 95
Thr Ile Gln Arg Thr Gln Gln Glu Asp Ser Ala Val Tyr Leu Cys Ala
100 105 110
Ser Ser Pro Ile Gln Gly Glu Asn Ser Pro Leu His Phe Gly Asn Gly
115 120 125
Thr Arg Leu Thr Val Thr
130
<210> 365
<211> 267
<212> PRT
<213> 智人(Homo sapiens)
<400> 365
Met Ala Lys His Leu Thr Thr Phe Leu Val Ile Leu Trp Leu Tyr Phe
1 5 10 15
Tyr Arg Gly Asn Gly Lys Asn Gln Val Glu Gln Ser Pro Gln Ser Leu
20 25 30
Ile Ile Leu Glu Gly Lys Asn Cys Thr Leu Gln Cys Asn Tyr Thr Val
35 40 45
Ser Pro Phe Ser Asn Leu Arg Trp Tyr Lys Gln Asp Thr Gly Arg Gly
50 55 60
Pro Val Ser Leu Thr Ile Met Thr Phe Ser Glu Asn Thr Lys Ser Asn
65 70 75 80
Gly Arg Tyr Thr Ala Thr Leu Asp Ala Asp Thr Lys Gln Ser Ser Leu
85 90 95
His Ile Thr Ala Ser Gln Leu Ser Asp Ser Ala Ser Tyr Ile Cys Val
100 105 110
Val Ser Ser Tyr Lys Leu Ile Phe Gly Thr Gly Thr Arg Leu Gln Val
115 120 125
Phe Pro Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr Gln Leu Lys Asp
130 135 140
Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr Asp Phe Asp Ser
145 150 155 160
Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr Phe Ile Thr Asp
165 170 175
Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys Ser Asn Gly Ala
180 185 190
Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln Asp Ile Phe Lys
195 200 205
Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro Cys Asp Ala Thr
210 215 220
Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu Asn Phe Gln Asn
225 230 235 240
Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys Val Ala Gly Phe
245 250 255
Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser
260 265
<210> 366
<211> 307
<212> PRT
<213> 智人(Homo sapiens)
<400> 366
Met His Thr Arg Leu Leu Phe Trp Val Ala Phe Cys Leu Leu Gly Ala
1 5 10 15
Tyr His Thr Gly Ala Gly Val Ser Gln Ser Pro Ser Asn Lys Val Thr
20 25 30
Glu Lys Gly Lys Asp Val Glu Leu Arg Cys Asp Pro Ile Ser Gly His
35 40 45
Thr Ala Leu Tyr Trp Tyr Arg Gln Arg Leu Gly Gln Gly Leu Glu Phe
50 55 60
Leu Ile Tyr Phe Gln Gly Asn Ser Ala Pro Asp Lys Ser Gly Leu Pro
65 70 75 80
Ser Asp Arg Phe Ser Ala Glu Arg Thr Gly Glu Ser Val Ser Thr Leu
85 90 95
Thr Ile Gln Arg Thr Gln Gln Glu Asp Ser Ala Val Tyr Leu Cys Ala
100 105 110
Ser Ser Pro Ile Gln Gly Glu Asn Ser Pro Leu His Phe Gly Asn Gly
115 120 125
Thr Arg Leu Thr Val Thr Glu Asp Leu Arg Asn Val Thr Pro Pro Lys
130 135 140
Val Ser Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys
145 150 155 160
Ala Thr Leu Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu
165 170 175
Leu Ser Trp Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr
180 185 190
Asp Pro Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser
195 200 205
Arg Leu Arg Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe
210 215 220
Arg Cys Gln Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro
225 230 235 240
Glu Gly Ser Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp
245 250 255
Gly Arg Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val
260 265 270
Leu Ser Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu
275 280 285
Tyr Ala Val Leu Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg
290 295 300
Lys Asn Ser
305
<210> 367
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 367
Ser Ser Val Ser Val Tyr
1 5
<210> 368
<211> 8
<212> PRT
<213> 智人(Homo sapiens)
<400> 368
Tyr Leu Ser Gly Ser Thr Leu Val
1 5
<210> 369
<211> 14
<212> PRT
<213> 智人(Homo sapiens)
<400> 369
Cys Ala Val Ser Lys Gly Thr Gly Ala Gln Lys Leu Val Phe
1 5 10
<210> 370
<211> 5
<212> PRT
<213> 智人(Homo sapiens)
<400> 370
Leu Asn His Asp Ala
1 5
<210> 371
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 371
Ser Gln Ile Val Asn Asp
1 5
<210> 372
<211> 7
<212> PRT
<213> 智人(Homo sapiens)
<400> 372
Cys Ala Ser Glu Ala Phe Phe
1 5
<210> 373
<211> 133
<212> PRT
<213> 智人(Homo sapiens)
<400> 373
Met Ala Leu Leu Leu Val Pro Ala Phe Gln Val Ile Phe Thr Leu Gly
1 5 10 15
Gly Thr Arg Ala Gln Ser Val Thr Gln Leu Asp Ser Gln Val Pro Val
20 25 30
Phe Glu Glu Ala Pro Val Glu Leu Arg Cys Asn Tyr Ser Ser Ser Val
35 40 45
Ser Val Tyr Leu Phe Trp Tyr Val Gln Tyr Pro Asn Gln Gly Leu Gln
50 55 60
Leu Leu Leu Lys Tyr Leu Ser Gly Ser Thr Leu Val Glu Ser Ile Asn
65 70 75 80
Gly Phe Glu Ala Glu Phe Asn Lys Ser Gln Thr Ser Phe His Leu Arg
85 90 95
Lys Pro Ser Val His Ile Ser Asp Thr Ala Glu Tyr Phe Cys Ala Val
100 105 110
Ser Lys Gly Thr Gly Ala Gln Lys Leu Val Phe Gly Gln Gly Thr Arg
115 120 125
Leu Thr Ile Asn Pro
130
<210> 374
<211> 125
<212> PRT
<213> 智人(Homo sapiens)
<400> 374
Met His Asn Gln Val Leu Cys Cys Val Val Leu Cys Phe Leu Gly Ala
1 5 10 15
Asn Thr Val Asp Gly Gly Ile Thr Gln Ser Pro Lys Tyr Leu Phe Arg
20 25 30
Lys Glu Gly Gln Asn Val Thr Leu Ser Cys Glu Gln Asn Leu Asn His
35 40 45
Asp Ala Met Tyr Trp Tyr Arg Gln Asp Pro Gly Gln Gly Leu Arg Leu
50 55 60
Ile Tyr Tyr Ser Gln Ile Val Asn Asp Phe Gln Lys Gly Asp Ile Ala
65 70 75 80
Glu Gly Tyr Ser Val Ser Arg Glu Lys Lys Glu Ser Phe Pro Leu Ile
85 90 95
Val Thr Ser Ala Gln Lys Asn Pro Thr Ala Ser Tyr Leu Cys Ala Ser
100 105 110
Glu Ala Phe Phe Gly Gln Gly Thr Arg Leu Thr Val Val
115 120 125
<210> 375
<211> 270
<212> PRT
<213> 智人(Homo sapiens)
<400> 375
Met Ala Leu Leu Leu Val Pro Ala Phe Gln Val Ile Phe Thr Leu Gly
1 5 10 15
Gly Thr Arg Ala Gln Ser Val Thr Gln Leu Asp Ser Gln Val Pro Val
20 25 30
Phe Glu Glu Ala Pro Val Glu Leu Arg Cys Asn Tyr Ser Ser Ser Val
35 40 45
Ser Val Tyr Leu Phe Trp Tyr Val Gln Tyr Pro Asn Gln Gly Leu Gln
50 55 60
Leu Leu Leu Lys Tyr Leu Ser Gly Ser Thr Leu Val Glu Ser Ile Asn
65 70 75 80
Gly Phe Glu Ala Glu Phe Asn Lys Ser Gln Thr Ser Phe His Leu Arg
85 90 95
Lys Pro Ser Val His Ile Ser Asp Thr Ala Glu Tyr Phe Cys Ala Val
100 105 110
Ser Lys Gly Thr Gly Ala Gln Lys Leu Val Phe Gly Gln Gly Thr Arg
115 120 125
Leu Thr Ile Asn Pro Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr Gln
130 135 140
Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr Asp
145 150 155 160
Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr Phe
165 170 175
Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys Ser
180 185 190
Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln Asp
195 200 205
Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro Cys
210 215 220
Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu Asn
225 230 235 240
Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys Val
245 250 255
Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser
260 265 270
<210> 376
<211> 298
<212> PRT
<213> 智人(Homo sapiens)
<400> 376
Met His Asn Gln Val Leu Cys Cys Val Val Leu Cys Phe Leu Gly Ala
1 5 10 15
Asn Thr Val Asp Gly Gly Ile Thr Gln Ser Pro Lys Tyr Leu Phe Arg
20 25 30
Lys Glu Gly Gln Asn Val Thr Leu Ser Cys Glu Gln Asn Leu Asn His
35 40 45
Asp Ala Met Tyr Trp Tyr Arg Gln Asp Pro Gly Gln Gly Leu Arg Leu
50 55 60
Ile Tyr Tyr Ser Gln Ile Val Asn Asp Phe Gln Lys Gly Asp Ile Ala
65 70 75 80
Glu Gly Tyr Ser Val Ser Arg Glu Lys Lys Glu Ser Phe Pro Leu Ile
85 90 95
Val Thr Ser Ala Gln Lys Asn Pro Thr Ala Ser Tyr Leu Cys Ala Ser
100 105 110
Glu Ala Phe Phe Gly Gln Gly Thr Arg Leu Thr Val Val Glu Asp Leu
115 120 125
Arg Asn Val Thr Pro Pro Lys Val Ser Leu Phe Glu Pro Ser Lys Ala
130 135 140
Glu Ile Ala Asn Lys Gln Lys Ala Thr Leu Val Cys Leu Ala Arg Gly
145 150 155 160
Phe Phe Pro Asp His Val Glu Leu Ser Trp Trp Val Asn Gly Lys Glu
165 170 175
Val His Ser Gly Val Cys Thr Asp Pro Gln Ala Tyr Lys Glu Ser Asn
180 185 190
Tyr Ser Tyr Cys Leu Ser Ser Arg Leu Arg Val Ser Ala Thr Phe Trp
195 200 205
His Asn Pro Arg Asn His Phe Arg Cys Gln Val Gln Phe His Gly Leu
210 215 220
Ser Glu Glu Asp Lys Trp Pro Glu Gly Ser Pro Lys Pro Val Thr Gln
225 230 235 240
Asn Ile Ser Ala Glu Ala Trp Gly Arg Ala Asp Cys Gly Ile Thr Ser
245 250 255
Ala Ser Tyr Gln Gln Gly Val Leu Ser Ala Thr Ile Leu Tyr Glu Ile
260 265 270
Leu Leu Gly Lys Ala Thr Leu Tyr Ala Val Leu Val Ser Thr Leu Val
275 280 285
Val Met Ala Met Val Lys Arg Lys Asn Ser
290 295
<210> 377
<211> 7
<212> PRT
<213> 智人(Homo sapiens)
<400> 377
Thr Ile Ser Gly Thr Asp Tyr
1 5
<210> 378
<211> 5
<212> PRT
<213> 智人(Homo sapiens)
<400> 378
Gly Leu Thr Ser Asn
1 5
<210> 379
<211> 14
<212> PRT
<213> 智人(Homo sapiens)
<400> 379
Cys Ile Leu Ala Ser Gly Ala Gly Ser Tyr Gln Leu Thr Phe
1 5 10
<210> 380
<211> 5
<212> PRT
<213> 智人(Homo sapiens)
<400> 380
Leu Gly His Asp Thr
1 5
<210> 381
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 381
Tyr Asn Asn Lys Glu Leu
1 5
<210> 382
<211> 14
<212> PRT
<213> 智人(Homo sapiens)
<400> 382
Cys Ala Ser Arg Thr Ile Gly Tyr Asn Thr Glu Ala Phe Phe
1 5 10
<210> 383
<211> 128
<212> PRT
<213> 智人(Homo sapiens)
<400> 383
Met Ala Leu Val Thr Ser Ile Thr Val Leu Leu Ser Leu Gly Ile Met
1 5 10 15
Gly Asp Ala Lys Thr Thr Gln Pro Asn Ser Met Glu Ser Asn Glu Glu
20 25 30
Glu Pro Val His Leu Pro Cys Asn His Ser Thr Ile Ser Gly Thr Asp
35 40 45
Tyr Ile His Trp Tyr Arg Gln Leu Pro Ser Gln Gly Pro Glu Tyr Val
50 55 60
Ile His Gly Leu Thr Ser Asn Val Asn Asn Arg Met Ala Ser Leu Ala
65 70 75 80
Ile Ala Glu Asp Arg Lys Ser Ser Thr Leu Ile Leu His Arg Ala Thr
85 90 95
Leu Arg Asp Ala Ala Val Tyr Tyr Cys Ile Leu Ala Ser Gly Ala Gly
100 105 110
Ser Tyr Gln Leu Thr Phe Gly Lys Gly Thr Lys Leu Ser Val Ile Pro
115 120 125
<210> 384
<211> 132
<212> PRT
<213> 智人(Homo sapiens)
<400> 384
Met His Cys Arg Leu Leu Cys Cys Val Val Phe Cys Leu Leu Gln Ala
1 5 10 15
Gly Pro Leu Asp Thr Ala Val Ser Gln Thr Pro Lys Tyr Leu Val Thr
20 25 30
Gln Met Gly Asn Asp Lys Ser Ile Lys Cys Glu Gln Asn Leu Gly His
35 40 45
Asp Thr Met Tyr Trp Tyr Lys Gln Asp Ser Lys Lys Phe Leu Lys Ile
50 55 60
Met Phe Ser Tyr Asn Asn Lys Glu Leu Ile Ile Asn Glu Thr Val Pro
65 70 75 80
Asn Arg Phe Ser Pro Lys Ser Pro Asp Lys Ala His Leu Asn Leu His
85 90 95
Ile Asn Ser Leu Glu Leu Gly Asp Ser Ala Val Tyr Phe Cys Ala Ser
100 105 110
Arg Thr Ile Gly Tyr Asn Thr Glu Ala Phe Phe Gly Gln Gly Thr Arg
115 120 125
Leu Thr Val Val
130
<210> 385
<211> 265
<212> PRT
<213> 智人(Homo sapiens)
<400> 385
Met Ala Leu Val Thr Ser Ile Thr Val Leu Leu Ser Leu Gly Ile Met
1 5 10 15
Gly Asp Ala Lys Thr Thr Gln Pro Asn Ser Met Glu Ser Asn Glu Glu
20 25 30
Glu Pro Val His Leu Pro Cys Asn His Ser Thr Ile Ser Gly Thr Asp
35 40 45
Tyr Ile His Trp Tyr Arg Gln Leu Pro Ser Gln Gly Pro Glu Tyr Val
50 55 60
Ile His Gly Leu Thr Ser Asn Val Asn Asn Arg Met Ala Ser Leu Ala
65 70 75 80
Ile Ala Glu Asp Arg Lys Ser Ser Thr Leu Ile Leu His Arg Ala Thr
85 90 95
Leu Arg Asp Ala Ala Val Tyr Tyr Cys Ile Leu Ala Ser Gly Ala Gly
100 105 110
Ser Tyr Gln Leu Thr Phe Gly Lys Gly Thr Lys Leu Ser Val Ile Pro
115 120 125
Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr Gln Leu Lys Asp Pro Arg
130 135 140
Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr Asp Phe Asp Ser Gln Ile
145 150 155 160
Asn Val Pro Lys Thr Met Glu Ser Gly Thr Phe Ile Thr Asp Lys Cys
165 170 175
Val Leu Asp Met Lys Ala Met Asp Ser Lys Ser Asn Gly Ala Ile Ala
180 185 190
Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln Asp Ile Phe Lys Glu Thr
195 200 205
Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro Cys Asp Ala Thr Leu Thr
210 215 220
Glu Lys Ser Phe Glu Thr Asp Met Asn Leu Asn Phe Gln Asn Leu Leu
225 230 235 240
Val Ile Val Leu Arg Ile Leu Leu Leu Lys Val Ala Gly Phe Asn Leu
245 250 255
Leu Met Thr Leu Arg Leu Trp Ser Ser
260 265
<210> 386
<211> 305
<212> PRT
<213> 智人(Homo sapiens)
<400> 386
Met His Cys Arg Leu Leu Cys Cys Val Val Phe Cys Leu Leu Gln Ala
1 5 10 15
Gly Pro Leu Asp Thr Ala Val Ser Gln Thr Pro Lys Tyr Leu Val Thr
20 25 30
Gln Met Gly Asn Asp Lys Ser Ile Lys Cys Glu Gln Asn Leu Gly His
35 40 45
Asp Thr Met Tyr Trp Tyr Lys Gln Asp Ser Lys Lys Phe Leu Lys Ile
50 55 60
Met Phe Ser Tyr Asn Asn Lys Glu Leu Ile Ile Asn Glu Thr Val Pro
65 70 75 80
Asn Arg Phe Ser Pro Lys Ser Pro Asp Lys Ala His Leu Asn Leu His
85 90 95
Ile Asn Ser Leu Glu Leu Gly Asp Ser Ala Val Tyr Phe Cys Ala Ser
100 105 110
Arg Thr Ile Gly Tyr Asn Thr Glu Ala Phe Phe Gly Gln Gly Thr Arg
115 120 125
Leu Thr Val Val Glu Asp Leu Arg Asn Val Thr Pro Pro Lys Val Ser
130 135 140
Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys Ala Thr
145 150 155 160
Leu Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu Leu Ser
165 170 175
Trp Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr Asp Pro
180 185 190
Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser Arg Leu
195 200 205
Arg Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe Arg Cys
210 215 220
Gln Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro Glu Gly
225 230 235 240
Ser Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp Gly Arg
245 250 255
Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val Leu Ser
260 265 270
Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu Tyr Ala
275 280 285
Val Leu Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg Lys Asn
290 295 300
Ser
305
<210> 387
<211> 5
<212> PRT
<213> 智人(Homo sapiens)
<400> 387
Val Gly Ile Ser Ala
1 5
<210> 388
<211> 5
<212> PRT
<213> 智人(Homo sapiens)
<400> 388
Leu Ser Ser Gly Lys
1 5
<210> 389
<211> 13
<212> PRT
<213> 智人(Homo sapiens)
<400> 389
Cys Ala Ala Leu Ser Tyr Asn Thr Asp Lys Leu Ile Phe
1 5 10
<210> 390
<211> 5
<212> PRT
<213> 智人(Homo sapiens)
<400> 390
Ser Gly His Thr Ala
1 5
<210> 391
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 391
Phe Gln Gly Thr Gly Ala
1 5
<210> 392
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 392
Cys Ala Ser Ser Leu Ser Gly Leu Leu Gln Glu Thr Gln Tyr Phe
1 5 10 15
<210> 393
<211> 131
<212> PRT
<213> 智人(Homo sapiens)
<400> 393
Met Ala Lys Ile Arg Gln Phe Leu Leu Ala Ile Leu Trp Leu Gln Leu
1 5 10 15
Ser Cys Val Ser Ala Ala Lys Asn Glu Val Glu Gln Ser Pro Gln Asn
20 25 30
Leu Thr Ala Gln Glu Gly Glu Phe Ile Thr Ile Asn Cys Ser Tyr Ser
35 40 45
Val Gly Ile Ser Ala Leu His Trp Leu Gln Gln His Pro Gly Gly Gly
50 55 60
Ile Val Ser Leu Phe Met Leu Ser Ser Gly Lys Lys Lys His Gly Arg
65 70 75 80
Leu Ile Ala Thr Ile Asn Ile Gln Glu Lys His Ser Ser Leu His Ile
85 90 95
Thr Ala Ser His Pro Arg Asp Ser Ala Val Tyr Ile Cys Ala Ala Leu
100 105 110
Ser Tyr Asn Thr Asp Lys Leu Ile Phe Gly Thr Gly Thr Arg Leu Gln
115 120 125
Val Phe Pro
130
<210> 394
<211> 134
<212> PRT
<213> 智人(Homo sapiens)
<400> 394
Met His Thr Arg Leu Leu Cys Trp Ala Ala Leu Cys Leu Leu Gly Ala
1 5 10 15
Asp His Thr Gly Ala Gly Val Ser Gln Thr Pro Ser Asn Lys Val Thr
20 25 30
Glu Lys Gly Lys Tyr Val Glu Leu Arg Cys Asp Pro Ile Ser Gly His
35 40 45
Thr Ala Leu Tyr Trp Tyr Arg Gln Ser Leu Gly Gln Gly Pro Glu Phe
50 55 60
Leu Ile Tyr Phe Gln Gly Thr Gly Ala Ala Asp Asp Ser Gly Leu Pro
65 70 75 80
Asn Asp Arg Phe Phe Ala Val Arg Pro Glu Gly Ser Val Ser Thr Leu
85 90 95
Lys Ile Gln Arg Thr Glu Arg Gly Asp Ser Ala Val Tyr Leu Cys Ala
100 105 110
Ser Ser Leu Ser Gly Leu Leu Gln Glu Thr Gln Tyr Phe Gly Pro Gly
115 120 125
Thr Arg Leu Leu Val Leu
130
<210> 395
<211> 268
<212> PRT
<213> 智人(Homo sapiens)
<400> 395
Met Ala Lys Ile Arg Gln Phe Leu Leu Ala Ile Leu Trp Leu Gln Leu
1 5 10 15
Ser Cys Val Ser Ala Ala Lys Asn Glu Val Glu Gln Ser Pro Gln Asn
20 25 30
Leu Thr Ala Gln Glu Gly Glu Phe Ile Thr Ile Asn Cys Ser Tyr Ser
35 40 45
Val Gly Ile Ser Ala Leu His Trp Leu Gln Gln His Pro Gly Gly Gly
50 55 60
Ile Val Ser Leu Phe Met Leu Ser Ser Gly Lys Lys Lys His Gly Arg
65 70 75 80
Leu Ile Ala Thr Ile Asn Ile Gln Glu Lys His Ser Ser Leu His Ile
85 90 95
Thr Ala Ser His Pro Arg Asp Ser Ala Val Tyr Ile Cys Ala Ala Leu
100 105 110
Ser Tyr Asn Thr Asp Lys Leu Ile Phe Gly Thr Gly Thr Arg Leu Gln
115 120 125
Val Phe Pro Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr Gln Leu Lys
130 135 140
Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr Asp Phe Asp
145 150 155 160
Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr Phe Ile Thr
165 170 175
Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys Ser Asn Gly
180 185 190
Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln Asp Ile Phe
195 200 205
Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro Cys Asp Ala
210 215 220
Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu Asn Phe Gln
225 230 235 240
Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys Val Ala Gly
245 250 255
Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser
260 265
<210> 396
<211> 307
<212> PRT
<213> 智人(Homo sapiens)
<400> 396
Met His Thr Arg Leu Leu Cys Trp Ala Ala Leu Cys Leu Leu Gly Ala
1 5 10 15
Asp His Thr Gly Ala Gly Val Ser Gln Thr Pro Ser Asn Lys Val Thr
20 25 30
Glu Lys Gly Lys Tyr Val Glu Leu Arg Cys Asp Pro Ile Ser Gly His
35 40 45
Thr Ala Leu Tyr Trp Tyr Arg Gln Ser Leu Gly Gln Gly Pro Glu Phe
50 55 60
Leu Ile Tyr Phe Gln Gly Thr Gly Ala Ala Asp Asp Ser Gly Leu Pro
65 70 75 80
Asn Asp Arg Phe Phe Ala Val Arg Pro Glu Gly Ser Val Ser Thr Leu
85 90 95
Lys Ile Gln Arg Thr Glu Arg Gly Asp Ser Ala Val Tyr Leu Cys Ala
100 105 110
Ser Ser Leu Ser Gly Leu Leu Gln Glu Thr Gln Tyr Phe Gly Pro Gly
115 120 125
Thr Arg Leu Leu Val Leu Glu Asp Leu Arg Asn Val Thr Pro Pro Lys
130 135 140
Val Ser Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys
145 150 155 160
Ala Thr Leu Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu
165 170 175
Leu Ser Trp Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr
180 185 190
Asp Pro Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser
195 200 205
Arg Leu Arg Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe
210 215 220
Arg Cys Gln Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro
225 230 235 240
Glu Gly Ser Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp
245 250 255
Gly Arg Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val
260 265 270
Leu Ser Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu
275 280 285
Tyr Ala Val Leu Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg
290 295 300
Lys Asn Ser
305
<210> 397
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 397
Ala Thr Gly Tyr Pro Ser
1 5
<210> 398
<211> 7
<212> PRT
<213> 智人(Homo sapiens)
<400> 398
Ala Thr Lys Ala Asp Asp Lys
1 5
<210> 399
<211> 16
<212> PRT
<213> 智人(Homo sapiens)
<400> 399
Cys Ala Leu Ser His Thr Gly Ser Ser Asn Thr Gly Lys Leu Ile Phe
1 5 10 15
<210> 400
<211> 5
<212> PRT
<213> 智人(Homo sapiens)
<400> 400
Ser Gly His Ala Thr
1 5
<210> 401
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 401
Phe Gln Asn Asn Gly Val
1 5
<210> 402
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 402
Cys Ala Ser Ser Thr Gly Gly Gly Arg His Gln Pro Gln His Phe
1 5 10 15
<210> 403
<211> 134
<212> PRT
<213> 智人(Homo sapiens)
<400> 403
Met Ala Tyr Ser Pro Gly Leu Val Ser Leu Ile Leu Leu Leu Leu Gly
1 5 10 15
Arg Thr Arg Gly Asn Ser Val Thr Gln Met Glu Gly Pro Val Thr Leu
20 25 30
Ser Glu Glu Ala Phe Leu Thr Ile Asn Cys Thr Tyr Thr Ala Thr Gly
35 40 45
Tyr Pro Ser Leu Phe Trp Tyr Val Gln Tyr Pro Gly Glu Gly Leu Gln
50 55 60
Leu Leu Leu Lys Ala Thr Lys Ala Asp Asp Lys Gly Ser Asn Lys Gly
65 70 75 80
Phe Glu Ala Thr Tyr Arg Lys Glu Thr Thr Ser Phe His Leu Glu Lys
85 90 95
Gly Ser Val Gln Val Ser Asp Ser Ala Val Tyr Phe Cys Ala Leu Ser
100 105 110
His Thr Gly Ser Ser Asn Thr Gly Lys Leu Ile Phe Gly Gln Gly Thr
115 120 125
Arg Leu Gln Val Lys Pro
130
<210> 404
<211> 134
<212> PRT
<213> 智人(Homo sapiens)
<400> 404
Met His Thr Arg Leu Leu Cys Trp Ala Ala Leu Cys Leu Leu Gly Ala
1 5 10 15
Glu Leu Thr Glu Ala Gly Val Ala Gln Ser Pro Arg Tyr Lys Ile Ile
20 25 30
Glu Lys Arg Gln Ser Val Ala Phe Trp Cys Asn Pro Ile Ser Gly His
35 40 45
Ala Thr Leu Tyr Trp Tyr Gln Gln Ile Leu Gly Gln Gly Pro Lys Leu
50 55 60
Leu Ile Gln Phe Gln Asn Asn Gly Val Val Asp Asp Ser Gln Leu Pro
65 70 75 80
Lys Asp Arg Phe Ser Ala Glu Arg Leu Lys Gly Val Asp Ser Thr Leu
85 90 95
Lys Ile Gln Pro Ala Lys Leu Glu Asp Ser Ala Val Tyr Leu Cys Ala
100 105 110
Ser Ser Thr Gly Gly Gly Arg His Gln Pro Gln His Phe Gly Asp Gly
115 120 125
Thr Arg Leu Ser Ile Leu
130
<210> 405
<211> 271
<212> PRT
<213> 智人(Homo sapiens)
<400> 405
Met Ala Tyr Ser Pro Gly Leu Val Ser Leu Ile Leu Leu Leu Leu Gly
1 5 10 15
Arg Thr Arg Gly Asn Ser Val Thr Gln Met Glu Gly Pro Val Thr Leu
20 25 30
Ser Glu Glu Ala Phe Leu Thr Ile Asn Cys Thr Tyr Thr Ala Thr Gly
35 40 45
Tyr Pro Ser Leu Phe Trp Tyr Val Gln Tyr Pro Gly Glu Gly Leu Gln
50 55 60
Leu Leu Leu Lys Ala Thr Lys Ala Asp Asp Lys Gly Ser Asn Lys Gly
65 70 75 80
Phe Glu Ala Thr Tyr Arg Lys Glu Thr Thr Ser Phe His Leu Glu Lys
85 90 95
Gly Ser Val Gln Val Ser Asp Ser Ala Val Tyr Phe Cys Ala Leu Ser
100 105 110
His Thr Gly Ser Ser Asn Thr Gly Lys Leu Ile Phe Gly Gln Gly Thr
115 120 125
Arg Leu Gln Val Lys Pro Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr
130 135 140
Gln Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr
145 150 155 160
Asp Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr
165 170 175
Phe Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys
180 185 190
Ser Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln
195 200 205
Asp Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro
210 215 220
Cys Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu
225 230 235 240
Asn Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys
245 250 255
Val Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser
260 265 270
<210> 406
<211> 307
<212> PRT
<213> 智人(Homo sapiens)
<400> 406
Met His Thr Arg Leu Leu Cys Trp Ala Ala Leu Cys Leu Leu Gly Ala
1 5 10 15
Glu Leu Thr Glu Ala Gly Val Ala Gln Ser Pro Arg Tyr Lys Ile Ile
20 25 30
Glu Lys Arg Gln Ser Val Ala Phe Trp Cys Asn Pro Ile Ser Gly His
35 40 45
Ala Thr Leu Tyr Trp Tyr Gln Gln Ile Leu Gly Gln Gly Pro Lys Leu
50 55 60
Leu Ile Gln Phe Gln Asn Asn Gly Val Val Asp Asp Ser Gln Leu Pro
65 70 75 80
Lys Asp Arg Phe Ser Ala Glu Arg Leu Lys Gly Val Asp Ser Thr Leu
85 90 95
Lys Ile Gln Pro Ala Lys Leu Glu Asp Ser Ala Val Tyr Leu Cys Ala
100 105 110
Ser Ser Thr Gly Gly Gly Arg His Gln Pro Gln His Phe Gly Asp Gly
115 120 125
Thr Arg Leu Ser Ile Leu Glu Asp Leu Arg Asn Val Thr Pro Pro Lys
130 135 140
Val Ser Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys
145 150 155 160
Ala Thr Leu Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu
165 170 175
Leu Ser Trp Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr
180 185 190
Asp Pro Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser
195 200 205
Arg Leu Arg Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe
210 215 220
Arg Cys Gln Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro
225 230 235 240
Glu Gly Ser Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp
245 250 255
Gly Arg Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val
260 265 270
Leu Ser Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu
275 280 285
Tyr Ala Val Leu Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg
290 295 300
Lys Asn Ser
305
<210> 407
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 407
Ala Thr Gly Tyr Pro Ser
1 5
<210> 408
<211> 7
<212> PRT
<213> 智人(Homo sapiens)
<400> 408
Ala Thr Lys Ala Asp Asp Lys
1 5
<210> 409
<211> 16
<212> PRT
<213> 智人(Homo sapiens)
<400> 409
Cys Ala Leu Ser Gln Thr Gly Ser Ser Lys Thr Gly Lys Leu Ile Phe
1 5 10 15
<210> 410
<211> 5
<212> PRT
<213> 智人(Homo sapiens)
<400> 410
Ser Gly His Ala Thr
1 5
<210> 411
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 411
Phe Gln Asn Asn Gly Val
1 5
<210> 412
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 412
Cys Ala Ser Ser Thr Gly Gly Gly Arg His Gln Pro Gln His Phe
1 5 10 15
<210> 413
<211> 134
<212> PRT
<213> 智人(Homo sapiens)
<400> 413
Met Ala Tyr Ser Pro Gly Leu Val Ser Leu Ile Leu Leu Leu Leu Gly
1 5 10 15
Arg Thr Arg Gly Asn Ser Val Thr Gln Met Glu Gly Pro Val Thr Leu
20 25 30
Ser Glu Glu Ala Phe Leu Thr Ile Asn Cys Thr Tyr Thr Ala Thr Gly
35 40 45
Tyr Pro Ser Leu Phe Trp Tyr Val Gln Tyr Pro Gly Glu Gly Leu Gln
50 55 60
Leu Leu Leu Lys Ala Thr Lys Ala Asp Asp Lys Gly Ser Asn Lys Gly
65 70 75 80
Phe Glu Ala Thr Tyr Arg Lys Glu Thr Thr Ser Phe His Leu Glu Lys
85 90 95
Gly Ser Val Gln Val Ser Asp Ser Ala Val Tyr Phe Cys Ala Leu Ser
100 105 110
Gln Thr Gly Ser Ser Lys Thr Gly Lys Leu Ile Phe Gly Gln Gly Thr
115 120 125
Arg Leu Gln Val Lys Pro
130
<210> 414
<211> 134
<212> PRT
<213> 智人(Homo sapiens)
<400> 414
Met His Thr Arg Leu Leu Cys Trp Ala Ala Leu Cys Leu Leu Gly Ala
1 5 10 15
Glu Leu Thr Glu Ala Gly Val Ala Gln Ser Pro Arg Tyr Lys Ile Ile
20 25 30
Glu Lys Arg Gln Ser Val Ala Phe Trp Cys Asn Pro Ile Ser Gly His
35 40 45
Ala Thr Leu Tyr Trp Tyr Gln Gln Ile Leu Gly Gln Gly Pro Lys Leu
50 55 60
Leu Ile Gln Phe Gln Asn Asn Gly Val Val Asp Asp Ser Gln Leu Pro
65 70 75 80
Lys Asp Arg Phe Ser Ala Glu Arg Leu Lys Gly Val Asp Ser Thr Leu
85 90 95
Lys Ile Gln Pro Ala Lys Leu Glu Asp Ser Ala Val Tyr Leu Cys Ala
100 105 110
Ser Ser Thr Gly Gly Gly Arg His Gln Pro Gln His Phe Gly Asp Gly
115 120 125
Thr Arg Leu Ser Ile Leu
130
<210> 415
<211> 271
<212> PRT
<213> 智人(Homo sapiens)
<400> 415
Met Ala Tyr Ser Pro Gly Leu Val Ser Leu Ile Leu Leu Leu Leu Gly
1 5 10 15
Arg Thr Arg Gly Asn Ser Val Thr Gln Met Glu Gly Pro Val Thr Leu
20 25 30
Ser Glu Glu Ala Phe Leu Thr Ile Asn Cys Thr Tyr Thr Ala Thr Gly
35 40 45
Tyr Pro Ser Leu Phe Trp Tyr Val Gln Tyr Pro Gly Glu Gly Leu Gln
50 55 60
Leu Leu Leu Lys Ala Thr Lys Ala Asp Asp Lys Gly Ser Asn Lys Gly
65 70 75 80
Phe Glu Ala Thr Tyr Arg Lys Glu Thr Thr Ser Phe His Leu Glu Lys
85 90 95
Gly Ser Val Gln Val Ser Asp Ser Ala Val Tyr Phe Cys Ala Leu Ser
100 105 110
Gln Thr Gly Ser Ser Lys Thr Gly Lys Leu Ile Phe Gly Gln Gly Thr
115 120 125
Arg Leu Gln Val Lys Pro Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr
130 135 140
Gln Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr
145 150 155 160
Asp Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr
165 170 175
Phe Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys
180 185 190
Ser Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln
195 200 205
Asp Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro
210 215 220
Cys Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu
225 230 235 240
Asn Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys
245 250 255
Val Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser
260 265 270
<210> 416
<211> 307
<212> PRT
<213> 智人(Homo sapiens)
<400> 416
Met His Thr Arg Leu Leu Cys Trp Ala Ala Leu Cys Leu Leu Gly Ala
1 5 10 15
Glu Leu Thr Glu Ala Gly Val Ala Gln Ser Pro Arg Tyr Lys Ile Ile
20 25 30
Glu Lys Arg Gln Ser Val Ala Phe Trp Cys Asn Pro Ile Ser Gly His
35 40 45
Ala Thr Leu Tyr Trp Tyr Gln Gln Ile Leu Gly Gln Gly Pro Lys Leu
50 55 60
Leu Ile Gln Phe Gln Asn Asn Gly Val Val Asp Asp Ser Gln Leu Pro
65 70 75 80
Lys Asp Arg Phe Ser Ala Glu Arg Leu Lys Gly Val Asp Ser Thr Leu
85 90 95
Lys Ile Gln Pro Ala Lys Leu Glu Asp Ser Ala Val Tyr Leu Cys Ala
100 105 110
Ser Ser Thr Gly Gly Gly Arg His Gln Pro Gln His Phe Gly Asp Gly
115 120 125
Thr Arg Leu Ser Ile Leu Glu Asp Leu Arg Asn Val Thr Pro Pro Lys
130 135 140
Val Ser Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys
145 150 155 160
Ala Thr Leu Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu
165 170 175
Leu Ser Trp Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr
180 185 190
Asp Pro Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser
195 200 205
Arg Leu Arg Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe
210 215 220
Arg Cys Gln Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro
225 230 235 240
Glu Gly Ser Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp
245 250 255
Gly Arg Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val
260 265 270
Leu Ser Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu
275 280 285
Tyr Ala Val Leu Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg
290 295 300
Lys Asn Ser
305
<210> 417
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 417
Ala Thr Gly Tyr Pro Ser
1 5
<210> 418
<211> 7
<212> PRT
<213> 智人(Homo sapiens)
<400> 418
Ala Thr Lys Ala Asp Asp Lys
1 5
<210> 419
<211> 16
<212> PRT
<213> 智人(Homo sapiens)
<400> 419
Cys Ala Leu Ser Gln Thr Gly Ser Ser Asn Thr Gly Lys Leu Ile Phe
1 5 10 15
<210> 420
<211> 5
<212> PRT
<213> 智人(Homo sapiens)
<400> 420
Ser Gly His Ala Thr
1 5
<210> 421
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 421
Phe Gln Asn Asn Gly Val
1 5
<210> 422
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 422
Cys Ala Ser Ser Thr Gly Gly Gly Arg His Gln Pro Gln His Phe
1 5 10 15
<210> 423
<211> 134
<212> PRT
<213> 智人(Homo sapiens)
<400> 423
Met Ala Tyr Ser Pro Gly Leu Val Ser Leu Ile Leu Leu Leu Leu Gly
1 5 10 15
Arg Thr Arg Gly Asn Ser Val Thr Gln Met Glu Gly Pro Val Thr Leu
20 25 30
Ser Glu Glu Ala Phe Leu Thr Ile Asn Cys Thr Tyr Thr Ala Thr Gly
35 40 45
Tyr Pro Ser Leu Phe Trp Tyr Val Gln Tyr Pro Gly Glu Gly Leu Gln
50 55 60
Leu Leu Leu Lys Ala Thr Lys Ala Asp Asp Lys Gly Ser Asn Lys Gly
65 70 75 80
Phe Glu Ala Thr Tyr Arg Lys Glu Thr Thr Ser Phe His Leu Glu Lys
85 90 95
Gly Ser Val Gln Val Ser Asp Ser Ala Val Tyr Phe Cys Ala Leu Ser
100 105 110
Gln Thr Gly Ser Ser Asn Thr Gly Lys Leu Ile Phe Gly Gln Gly Thr
115 120 125
Arg Leu Gln Val Lys Pro
130
<210> 424
<211> 134
<212> PRT
<213> 智人(Homo sapiens)
<400> 424
Met His Thr Arg Leu Leu Cys Trp Ala Ala Leu Cys Leu Leu Gly Ala
1 5 10 15
Glu Leu Thr Glu Ala Gly Val Ala Gln Ser Pro Arg Tyr Lys Ile Ile
20 25 30
Glu Lys Arg Gln Ser Val Ala Phe Trp Cys Asn Pro Ile Ser Gly His
35 40 45
Ala Thr Leu Tyr Trp Tyr Gln Gln Ile Leu Gly Gln Gly Pro Lys Leu
50 55 60
Leu Ile Gln Phe Gln Asn Asn Gly Val Val Asp Asp Ser Gln Leu Pro
65 70 75 80
Lys Asp Arg Phe Ser Ala Glu Arg Leu Lys Gly Val Asp Ser Thr Leu
85 90 95
Lys Ile Gln Pro Ala Lys Leu Glu Asp Ser Ala Val Tyr Leu Cys Ala
100 105 110
Ser Ser Thr Gly Gly Gly Arg His Gln Pro Gln His Phe Gly Asp Gly
115 120 125
Thr Arg Leu Ser Ile Leu
130
<210> 425
<211> 271
<212> PRT
<213> 智人(Homo sapiens)
<400> 425
Met Ala Tyr Ser Pro Gly Leu Val Ser Leu Ile Leu Leu Leu Leu Gly
1 5 10 15
Arg Thr Arg Gly Asn Ser Val Thr Gln Met Glu Gly Pro Val Thr Leu
20 25 30
Ser Glu Glu Ala Phe Leu Thr Ile Asn Cys Thr Tyr Thr Ala Thr Gly
35 40 45
Tyr Pro Ser Leu Phe Trp Tyr Val Gln Tyr Pro Gly Glu Gly Leu Gln
50 55 60
Leu Leu Leu Lys Ala Thr Lys Ala Asp Asp Lys Gly Ser Asn Lys Gly
65 70 75 80
Phe Glu Ala Thr Tyr Arg Lys Glu Thr Thr Ser Phe His Leu Glu Lys
85 90 95
Gly Ser Val Gln Val Ser Asp Ser Ala Val Tyr Phe Cys Ala Leu Ser
100 105 110
Gln Thr Gly Ser Ser Asn Thr Gly Lys Leu Ile Phe Gly Gln Gly Thr
115 120 125
Arg Leu Gln Val Lys Pro Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr
130 135 140
Gln Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr
145 150 155 160
Asp Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr
165 170 175
Phe Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys
180 185 190
Ser Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln
195 200 205
Asp Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro
210 215 220
Cys Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu
225 230 235 240
Asn Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys
245 250 255
Val Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser
260 265 270
<210> 426
<211> 307
<212> PRT
<213> 智人(Homo sapiens)
<400> 426
Met His Thr Arg Leu Leu Cys Trp Ala Ala Leu Cys Leu Leu Gly Ala
1 5 10 15
Glu Leu Thr Glu Ala Gly Val Ala Gln Ser Pro Arg Tyr Lys Ile Ile
20 25 30
Glu Lys Arg Gln Ser Val Ala Phe Trp Cys Asn Pro Ile Ser Gly His
35 40 45
Ala Thr Leu Tyr Trp Tyr Gln Gln Ile Leu Gly Gln Gly Pro Lys Leu
50 55 60
Leu Ile Gln Phe Gln Asn Asn Gly Val Val Asp Asp Ser Gln Leu Pro
65 70 75 80
Lys Asp Arg Phe Ser Ala Glu Arg Leu Lys Gly Val Asp Ser Thr Leu
85 90 95
Lys Ile Gln Pro Ala Lys Leu Glu Asp Ser Ala Val Tyr Leu Cys Ala
100 105 110
Ser Ser Thr Gly Gly Gly Arg His Gln Pro Gln His Phe Gly Asp Gly
115 120 125
Thr Arg Leu Ser Ile Leu Glu Asp Leu Arg Asn Val Thr Pro Pro Lys
130 135 140
Val Ser Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys
145 150 155 160
Ala Thr Leu Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu
165 170 175
Leu Ser Trp Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr
180 185 190
Asp Pro Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser
195 200 205
Arg Leu Arg Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe
210 215 220
Arg Cys Gln Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro
225 230 235 240
Glu Gly Ser Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp
245 250 255
Gly Arg Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val
260 265 270
Leu Ser Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu
275 280 285
Tyr Ala Val Leu Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg
290 295 300
Lys Asn Ser
305
<210> 427
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 427
Ala Thr Gly Tyr Pro Ser
1 5
<210> 428
<211> 7
<212> PRT
<213> 智人(Homo sapiens)
<400> 428
Ala Thr Lys Ala Asp Asp Lys
1 5
<210> 429
<211> 16
<212> PRT
<213> 智人(Homo sapiens)
<400> 429
Cys Ala Leu Ser Thr Thr Gly Ser Ser Asn Thr Gly Lys Leu Ile Phe
1 5 10 15
<210> 430
<211> 5
<212> PRT
<213> 智人(Homo sapiens)
<400> 430
Ser Gly His Ala Thr
1 5
<210> 431
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 431
Phe Gln Asn Asn Gly Val
1 5
<210> 432
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 432
Cys Ala Ser Ser Thr Gly Gly Gly Arg His Gln Pro Gln His Phe
1 5 10 15
<210> 433
<211> 134
<212> PRT
<213> 智人(Homo sapiens)
<400> 433
Met Ala Tyr Ser Pro Gly Leu Val Ser Leu Ile Leu Leu Leu Leu Gly
1 5 10 15
Arg Thr Arg Gly Asn Ser Val Thr Gln Met Glu Gly Pro Val Thr Leu
20 25 30
Ser Glu Glu Ala Phe Leu Thr Ile Asn Cys Thr Tyr Thr Ala Thr Gly
35 40 45
Tyr Pro Ser Leu Phe Trp Tyr Val Gln Tyr Pro Gly Glu Gly Leu Gln
50 55 60
Leu Leu Leu Lys Ala Thr Lys Ala Asp Asp Lys Gly Ser Asn Lys Gly
65 70 75 80
Phe Glu Ala Thr Tyr Arg Lys Glu Thr Thr Ser Phe His Leu Glu Lys
85 90 95
Gly Ser Val Gln Val Ser Asp Ser Ala Val Tyr Phe Cys Ala Leu Ser
100 105 110
Thr Thr Gly Ser Ser Asn Thr Gly Lys Leu Ile Phe Gly Gln Gly Thr
115 120 125
Thr Leu Gln Val Lys Pro
130
<210> 434
<211> 134
<212> PRT
<213> 智人(Homo sapiens)
<400> 434
Met His Thr Arg Leu Leu Cys Trp Ala Ala Leu Cys Leu Leu Gly Ala
1 5 10 15
Glu Leu Thr Glu Ala Gly Val Ala Gln Ser Pro Arg Tyr Lys Ile Ile
20 25 30
Glu Lys Arg Gln Ser Val Ala Phe Trp Cys Asn Pro Ile Ser Gly His
35 40 45
Ala Thr Leu Tyr Trp Tyr Gln Gln Ile Leu Gly Gln Gly Pro Lys Leu
50 55 60
Leu Ile Gln Phe Gln Asn Asn Gly Val Val Asp Asp Ser Gln Leu Pro
65 70 75 80
Lys Asp Arg Phe Ser Ala Glu Arg Leu Lys Gly Val Asp Ser Thr Leu
85 90 95
Lys Ile Gln Pro Ala Lys Leu Glu Asp Ser Ala Val Tyr Leu Cys Ala
100 105 110
Ser Ser Thr Gly Gly Gly Arg His Gln Pro Gln His Phe Gly Asp Gly
115 120 125
Thr Arg Leu Ser Ile Leu
130
<210> 435
<211> 271
<212> PRT
<213> 智人(Homo sapiens)
<400> 435
Met Ala Tyr Ser Pro Gly Leu Val Ser Leu Ile Leu Leu Leu Leu Gly
1 5 10 15
Arg Thr Arg Gly Asn Ser Val Thr Gln Met Glu Gly Pro Val Thr Leu
20 25 30
Ser Glu Glu Ala Phe Leu Thr Ile Asn Cys Thr Tyr Thr Ala Thr Gly
35 40 45
Tyr Pro Ser Leu Phe Trp Tyr Val Gln Tyr Pro Gly Glu Gly Leu Gln
50 55 60
Leu Leu Leu Lys Ala Thr Lys Ala Asp Asp Lys Gly Ser Asn Lys Gly
65 70 75 80
Phe Glu Ala Thr Tyr Arg Lys Glu Thr Thr Ser Phe His Leu Glu Lys
85 90 95
Gly Ser Val Gln Val Ser Asp Ser Ala Val Tyr Phe Cys Ala Leu Ser
100 105 110
Thr Thr Gly Ser Ser Asn Thr Gly Lys Leu Ile Phe Gly Gln Gly Thr
115 120 125
Thr Leu Gln Val Lys Pro Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr
130 135 140
Gln Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr
145 150 155 160
Asp Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr
165 170 175
Phe Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys
180 185 190
Ser Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln
195 200 205
Asp Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro
210 215 220
Cys Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu
225 230 235 240
Asn Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys
245 250 255
Val Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser
260 265 270
<210> 436
<211> 307
<212> PRT
<213> 智人(Homo sapiens)
<400> 436
Met His Thr Arg Leu Leu Cys Trp Ala Ala Leu Cys Leu Leu Gly Ala
1 5 10 15
Glu Leu Thr Glu Ala Gly Val Ala Gln Ser Pro Arg Tyr Lys Ile Ile
20 25 30
Glu Lys Arg Gln Ser Val Ala Phe Trp Cys Asn Pro Ile Ser Gly His
35 40 45
Ala Thr Leu Tyr Trp Tyr Gln Gln Ile Leu Gly Gln Gly Pro Lys Leu
50 55 60
Leu Ile Gln Phe Gln Asn Asn Gly Val Val Asp Asp Ser Gln Leu Pro
65 70 75 80
Lys Asp Arg Phe Ser Ala Glu Arg Leu Lys Gly Val Asp Ser Thr Leu
85 90 95
Lys Ile Gln Pro Ala Lys Leu Glu Asp Ser Ala Val Tyr Leu Cys Ala
100 105 110
Ser Ser Thr Gly Gly Gly Arg His Gln Pro Gln His Phe Gly Asp Gly
115 120 125
Thr Arg Leu Ser Ile Leu Glu Asp Leu Arg Asn Val Thr Pro Pro Lys
130 135 140
Val Ser Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys
145 150 155 160
Ala Thr Leu Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu
165 170 175
Leu Ser Trp Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr
180 185 190
Asp Pro Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser
195 200 205
Arg Leu Arg Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe
210 215 220
Arg Cys Gln Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro
225 230 235 240
Glu Gly Ser Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp
245 250 255
Gly Arg Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val
260 265 270
Leu Ser Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu
275 280 285
Tyr Ala Val Leu Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg
290 295 300
Lys Asn Ser
305
<210> 437
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 437
Asp Arg Gly Ser Gln Ser
1 5
<210> 438
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 438
Ile Tyr Ser Asn Gly Asp
1 5
<210> 439
<211> 14
<212> PRT
<213> 智人(Homo sapiens)
<400> 439
Cys Ala Val Thr Leu Cys Gly Gly Tyr Asn Lys Leu Ile Phe
1 5 10
<210> 440
<211> 5
<212> PRT
<213> 智人(Homo sapiens)
<400> 440
Leu Asn His Asp Ala
1 5
<210> 441
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 441
Ser Gln Ile Val Asn Asp
1 5
<210> 442
<211> 12
<212> PRT
<213> 智人(Homo sapiens)
<400> 442
Cys Ala Ser Ser Ser Arg Asp Tyr Glu Gln Tyr Phe
1 5 10
<210> 443
<211> 133
<212> PRT
<213> 智人(Homo sapiens)
<400> 443
Met Ala Ser Leu Arg Val Leu Leu Val Ile Leu Trp Leu Gln Leu Ser
1 5 10 15
Trp Val Trp Ser Gln Gln Lys Glu Val Glu Gln Asn Ser Gly Pro Leu
20 25 30
Ser Val Pro Glu Gly Ala Ile Ala Ser Leu Asn Cys Thr Tyr Ser Asp
35 40 45
Arg Gly Ser Gln Ser Phe Phe Trp Tyr Arg Gln Tyr Ser Gly Lys Ser
50 55 60
Pro Glu Leu Ile Met Phe Ile Tyr Ser Asn Gly Asp Lys Glu Asp Gly
65 70 75 80
Arg Phe Thr Ala Gln Leu Asn Lys Ala Ser Gln Tyr Val Ser Leu Leu
85 90 95
Ile Arg Asp Ser Gln Pro Ser Asp Ser Ala Thr Tyr Leu Cys Ala Val
100 105 110
Thr Leu Cys Gly Gly Tyr Asn Lys Leu Ile Phe Gly Ala Gly Thr Arg
115 120 125
Leu Ala Val His Pro
130
<210> 444
<211> 130
<212> PRT
<213> 智人(Homo sapiens)
<400> 444
Met His Asn Gln Val Leu Cys Cys Val Val Leu Cys Phe Leu Gly Ala
1 5 10 15
Asn Thr Val Asp Gly Gly Ile Thr Gln Ser Pro Lys Tyr Leu Phe Arg
20 25 30
Lys Glu Gly Gln Asn Val Thr Leu Ser Cys Glu Gln Asn Leu Asn His
35 40 45
Asp Ala Met Tyr Trp Tyr Arg Gln Asp Pro Gly Gln Gly Leu Arg Leu
50 55 60
Ile Tyr Tyr Ser Gln Ile Val Asn Asp Phe Gln Lys Gly Asp Ile Val
65 70 75 80
Glu Gly Tyr Ser Val Ser Arg Glu Lys Lys Glu Ser Phe Pro Leu Thr
85 90 95
Val Thr Ser Ala Gln Lys Asn Pro Thr Ala Phe Tyr Leu Cys Ala Ser
100 105 110
Ser Ser Arg Asp Tyr Glu Gln Tyr Phe Gly Pro Gly Thr Arg Leu Thr
115 120 125
Val Thr
130
<210> 445
<211> 270
<212> PRT
<213> 智人(Homo sapiens)
<400> 445
Met Ala Ser Leu Arg Val Leu Leu Val Ile Leu Trp Leu Gln Leu Ser
1 5 10 15
Trp Val Trp Ser Gln Gln Lys Glu Val Glu Gln Asn Ser Gly Pro Leu
20 25 30
Ser Val Pro Glu Gly Ala Ile Ala Ser Leu Asn Cys Thr Tyr Ser Asp
35 40 45
Arg Gly Ser Gln Ser Phe Phe Trp Tyr Arg Gln Tyr Ser Gly Lys Ser
50 55 60
Pro Glu Leu Ile Met Phe Ile Tyr Ser Asn Gly Asp Lys Glu Asp Gly
65 70 75 80
Arg Phe Thr Ala Gln Leu Asn Lys Ala Ser Gln Tyr Val Ser Leu Leu
85 90 95
Ile Arg Asp Ser Gln Pro Ser Asp Ser Ala Thr Tyr Leu Cys Ala Val
100 105 110
Thr Leu Cys Gly Gly Tyr Asn Lys Leu Ile Phe Gly Ala Gly Thr Arg
115 120 125
Leu Ala Val His Pro Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr Gln
130 135 140
Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr Asp
145 150 155 160
Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr Phe
165 170 175
Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys Ser
180 185 190
Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln Asp
195 200 205
Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro Cys
210 215 220
Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu Asn
225 230 235 240
Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys Val
245 250 255
Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser
260 265 270
<210> 446
<211> 303
<212> PRT
<213> 智人(Homo sapiens)
<400> 446
Met His Asn Gln Val Leu Cys Cys Val Val Leu Cys Phe Leu Gly Ala
1 5 10 15
Asn Thr Val Asp Gly Gly Ile Thr Gln Ser Pro Lys Tyr Leu Phe Arg
20 25 30
Lys Glu Gly Gln Asn Val Thr Leu Ser Cys Glu Gln Asn Leu Asn His
35 40 45
Asp Ala Met Tyr Trp Tyr Arg Gln Asp Pro Gly Gln Gly Leu Arg Leu
50 55 60
Ile Tyr Tyr Ser Gln Ile Val Asn Asp Phe Gln Lys Gly Asp Ile Val
65 70 75 80
Glu Gly Tyr Ser Val Ser Arg Glu Lys Lys Glu Ser Phe Pro Leu Thr
85 90 95
Val Thr Ser Ala Gln Lys Asn Pro Thr Ala Phe Tyr Leu Cys Ala Ser
100 105 110
Ser Ser Arg Asp Tyr Glu Gln Tyr Phe Gly Pro Gly Thr Arg Leu Thr
115 120 125
Val Thr Glu Asp Leu Arg Asn Val Thr Pro Pro Lys Val Ser Leu Phe
130 135 140
Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys Ala Thr Leu Val
145 150 155 160
Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu Leu Ser Trp Trp
165 170 175
Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr Asp Pro Gln Ala
180 185 190
Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser Arg Leu Arg Val
195 200 205
Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe Arg Cys Gln Val
210 215 220
Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro Glu Gly Ser Pro
225 230 235 240
Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp Gly Arg Ala Asp
245 250 255
Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val Leu Ser Ala Thr
260 265 270
Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu Tyr Ala Val Leu
275 280 285
Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg Lys Asn Ser
290 295 300
<210> 447
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 447
Asp Arg Gly Ser Gln Ser
1 5
<210> 448
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 448
Ile Tyr Ser Asn Gly Asp
1 5
<210> 449
<211> 14
<212> PRT
<213> 智人(Homo sapiens)
<400> 449
Cys Ala Val Thr Leu Ser Gly Gly Tyr Asn Lys Leu Ile Phe
1 5 10
<210> 450
<211> 5
<212> PRT
<213> 智人(Homo sapiens)
<400> 450
Leu Asn His Asp Ala
1 5
<210> 451
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 451
Ser Gln Ile Val Asn Asp
1 5
<210> 452
<211> 12
<212> PRT
<213> 智人(Homo sapiens)
<400> 452
Cys Ala Ser Ser Ser Arg Asp Tyr Glu Gln Tyr Phe
1 5 10
<210> 453
<211> 133
<212> PRT
<213> 智人(Homo sapiens)
<400> 453
Met Ala Ser Leu Arg Val Leu Leu Val Ile Leu Trp Leu Gln Leu Ser
1 5 10 15
Trp Val Trp Ser Gln Gln Lys Glu Val Glu Gln Asn Ser Gly Pro Leu
20 25 30
Ser Val Pro Glu Gly Ala Ile Ala Ser Leu Asn Cys Thr Tyr Ser Asp
35 40 45
Arg Gly Ser Gln Ser Phe Phe Trp Tyr Arg Gln Tyr Ser Gly Lys Ser
50 55 60
Pro Glu Leu Ile Met Phe Ile Tyr Ser Asn Gly Asp Lys Glu Asp Gly
65 70 75 80
Arg Phe Thr Ala Gln Leu Asn Lys Ala Ser Gln Tyr Val Ser Leu Leu
85 90 95
Ile Arg Asp Ser Gln Pro Ser Asp Ser Ala Thr Tyr Leu Cys Ala Val
100 105 110
Thr Leu Ser Gly Gly Tyr Asn Lys Leu Ile Phe Gly Ala Gly Thr Arg
115 120 125
Leu Ala Val His Pro
130
<210> 454
<211> 130
<212> PRT
<213> 智人(Homo sapiens)
<400> 454
Met His Asn Gln Val Leu Cys Cys Val Val Leu Cys Phe Leu Gly Ala
1 5 10 15
Asn Thr Val Asp Gly Gly Ile Thr Gln Ser Pro Lys Tyr Leu Phe Arg
20 25 30
Lys Glu Gly Gln Asn Val Thr Leu Ser Cys Glu Gln Asn Leu Asn His
35 40 45
Asp Ala Met Tyr Trp Tyr Arg Gln Asp Pro Gly Gln Gly Leu Arg Leu
50 55 60
Ile Tyr Tyr Ser Gln Ile Val Asn Asp Phe Gln Lys Gly Asp Ile Val
65 70 75 80
Glu Gly Tyr Ser Val Ser Arg Glu Lys Lys Glu Ser Phe Pro Leu Thr
85 90 95
Val Thr Ser Ala Gln Lys Asn Pro Thr Ala Phe Tyr Leu Cys Ala Ser
100 105 110
Ser Ser Arg Asp Tyr Glu Gln Tyr Phe Gly Pro Gly Thr Arg Leu Thr
115 120 125
Val Thr
130
<210> 455
<211> 270
<212> PRT
<213> 智人(Homo sapiens)
<400> 455
Met Ala Ser Leu Arg Val Leu Leu Val Ile Leu Trp Leu Gln Leu Ser
1 5 10 15
Trp Val Trp Ser Gln Gln Lys Glu Val Glu Gln Asn Ser Gly Pro Leu
20 25 30
Ser Val Pro Glu Gly Ala Ile Ala Ser Leu Asn Cys Thr Tyr Ser Asp
35 40 45
Arg Gly Ser Gln Ser Phe Phe Trp Tyr Arg Gln Tyr Ser Gly Lys Ser
50 55 60
Pro Glu Leu Ile Met Phe Ile Tyr Ser Asn Gly Asp Lys Glu Asp Gly
65 70 75 80
Arg Phe Thr Ala Gln Leu Asn Lys Ala Ser Gln Tyr Val Ser Leu Leu
85 90 95
Ile Arg Asp Ser Gln Pro Ser Asp Ser Ala Thr Tyr Leu Cys Ala Val
100 105 110
Thr Leu Ser Gly Gly Tyr Asn Lys Leu Ile Phe Gly Ala Gly Thr Arg
115 120 125
Leu Ala Val His Pro Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr Gln
130 135 140
Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr Asp
145 150 155 160
Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr Phe
165 170 175
Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys Ser
180 185 190
Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln Asp
195 200 205
Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro Cys
210 215 220
Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu Asn
225 230 235 240
Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys Val
245 250 255
Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser
260 265 270
<210> 456
<211> 303
<212> PRT
<213> 智人(Homo sapiens)
<400> 456
Met His Asn Gln Val Leu Cys Cys Val Val Leu Cys Phe Leu Gly Ala
1 5 10 15
Asn Thr Val Asp Gly Gly Ile Thr Gln Ser Pro Lys Tyr Leu Phe Arg
20 25 30
Lys Glu Gly Gln Asn Val Thr Leu Ser Cys Glu Gln Asn Leu Asn His
35 40 45
Asp Ala Met Tyr Trp Tyr Arg Gln Asp Pro Gly Gln Gly Leu Arg Leu
50 55 60
Ile Tyr Tyr Ser Gln Ile Val Asn Asp Phe Gln Lys Gly Asp Ile Val
65 70 75 80
Glu Gly Tyr Ser Val Ser Arg Glu Lys Lys Glu Ser Phe Pro Leu Thr
85 90 95
Val Thr Ser Ala Gln Lys Asn Pro Thr Ala Phe Tyr Leu Cys Ala Ser
100 105 110
Ser Ser Arg Asp Tyr Glu Gln Tyr Phe Gly Pro Gly Thr Arg Leu Thr
115 120 125
Val Thr Glu Asp Leu Arg Asn Val Thr Pro Pro Lys Val Ser Leu Phe
130 135 140
Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys Ala Thr Leu Val
145 150 155 160
Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu Leu Ser Trp Trp
165 170 175
Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr Asp Pro Gln Ala
180 185 190
Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser Arg Leu Arg Val
195 200 205
Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe Arg Cys Gln Val
210 215 220
Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro Glu Gly Ser Pro
225 230 235 240
Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp Gly Arg Ala Asp
245 250 255
Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val Leu Ser Ala Thr
260 265 270
Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu Tyr Ala Val Leu
275 280 285
Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg Lys Asn Ser
290 295 300
<210> 457
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 457
Asp Arg Gly Ser Gln Ser
1 5
<210> 458
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 458
Ile Tyr Ser Asn Gly Asp
1 5
<210> 459
<211> 12
<212> PRT
<213> 智人(Homo sapiens)
<400> 459
Cys Ala Val Asn Asp Ala Gly Asn Met Leu Thr Phe
1 5 10
<210> 460
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 460
Asp Phe Gln Ala Thr Thr
1 5
<210> 461
<211> 7
<212> PRT
<213> 智人(Homo sapiens)
<400> 461
Ser Asn Glu Gly Ser Lys Ala
1 5
<210> 462
<211> 13
<212> PRT
<213> 智人(Homo sapiens)
<400> 462
Cys Ser Ala Ala Gly Gln Ala Asn Thr Glu Ala Phe Phe
1 5 10
<210> 463
<211> 131
<212> PRT
<213> 智人(Homo sapiens)
<400> 463
Met His Ser Leu Arg Val Leu Leu Val Ile Leu Trp Leu Gln Leu Ser
1 5 10 15
Trp Val Trp Ser Gln Gln Lys Glu Val Glu Gln Asn Ser Gly Pro Leu
20 25 30
Ser Val Pro Glu Gly Ala Ile Ala Ser Leu Asn Cys Thr Tyr Ser Asp
35 40 45
Arg Gly Ser Gln Ser Phe Phe Trp Tyr Arg Gln Tyr Ser Gly Lys Ser
50 55 60
Pro Glu Leu Ile Met Phe Ile Tyr Ser Asn Gly Asp Lys Glu Asp Gly
65 70 75 80
Arg Phe Thr Ala Gln Leu Asn Lys Ala Ser Gln Tyr Val Ser Leu Leu
85 90 95
Ile Arg Asp Ser Gln Pro Ser Asp Ser Ala Thr Tyr Leu Cys Ala Val
100 105 110
Asn Asp Ala Gly Asn Met Leu Thr Phe Gly Gly Gly Thr Arg Leu Met
115 120 125
Val Lys Pro
130
<210> 464
<211> 140
<212> PRT
<213> 智人(Homo sapiens)
<400> 464
Met Ala Leu Leu Leu Leu Leu Leu Gly Pro Gly Ile Ser Leu Leu Leu
1 5 10 15
Pro Gly Ser Leu Ala Gly Ser Gly Leu Gly Ala Val Val Ser Gln His
20 25 30
Pro Ser Trp Val Ile Cys Lys Ser Gly Thr Ser Val Lys Ile Glu Cys
35 40 45
Arg Ser Leu Asp Phe Gln Ala Thr Thr Met Phe Trp Tyr Arg Gln Phe
50 55 60
Pro Lys Gln Ser Leu Met Leu Met Ala Thr Ser Asn Glu Gly Ser Lys
65 70 75 80
Ala Thr Tyr Glu Gln Gly Val Glu Lys Asp Lys Phe Leu Ile Asn His
85 90 95
Ala Ser Leu Thr Leu Ser Thr Leu Thr Val Thr Ser Ala His Pro Glu
100 105 110
Asp Ser Ser Phe Tyr Ile Cys Ser Ala Ala Gly Gln Ala Asn Thr Glu
115 120 125
Ala Phe Phe Gly Gln Gly Thr Arg Leu Thr Val Val
130 135 140
<210> 465
<211> 268
<212> PRT
<213> 智人(Homo sapiens)
<400> 465
Met His Ser Leu Arg Val Leu Leu Val Ile Leu Trp Leu Gln Leu Ser
1 5 10 15
Trp Val Trp Ser Gln Gln Lys Glu Val Glu Gln Asn Ser Gly Pro Leu
20 25 30
Ser Val Pro Glu Gly Ala Ile Ala Ser Leu Asn Cys Thr Tyr Ser Asp
35 40 45
Arg Gly Ser Gln Ser Phe Phe Trp Tyr Arg Gln Tyr Ser Gly Lys Ser
50 55 60
Pro Glu Leu Ile Met Phe Ile Tyr Ser Asn Gly Asp Lys Glu Asp Gly
65 70 75 80
Arg Phe Thr Ala Gln Leu Asn Lys Ala Ser Gln Tyr Val Ser Leu Leu
85 90 95
Ile Arg Asp Ser Gln Pro Ser Asp Ser Ala Thr Tyr Leu Cys Ala Val
100 105 110
Asn Asp Ala Gly Asn Met Leu Thr Phe Gly Gly Gly Thr Arg Leu Met
115 120 125
Val Lys Pro Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr Gln Leu Lys
130 135 140
Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr Asp Phe Asp
145 150 155 160
Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr Phe Ile Thr
165 170 175
Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys Ser Asn Gly
180 185 190
Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln Asp Ile Phe
195 200 205
Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro Cys Asp Ala
210 215 220
Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu Asn Phe Gln
225 230 235 240
Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys Val Ala Gly
245 250 255
Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser
260 265
<210> 466
<211> 313
<212> PRT
<213> 智人(Homo sapiens)
<400> 466
Met Ala Leu Leu Leu Leu Leu Leu Gly Pro Gly Ile Ser Leu Leu Leu
1 5 10 15
Pro Gly Ser Leu Ala Gly Ser Gly Leu Gly Ala Val Val Ser Gln His
20 25 30
Pro Ser Trp Val Ile Cys Lys Ser Gly Thr Ser Val Lys Ile Glu Cys
35 40 45
Arg Ser Leu Asp Phe Gln Ala Thr Thr Met Phe Trp Tyr Arg Gln Phe
50 55 60
Pro Lys Gln Ser Leu Met Leu Met Ala Thr Ser Asn Glu Gly Ser Lys
65 70 75 80
Ala Thr Tyr Glu Gln Gly Val Glu Lys Asp Lys Phe Leu Ile Asn His
85 90 95
Ala Ser Leu Thr Leu Ser Thr Leu Thr Val Thr Ser Ala His Pro Glu
100 105 110
Asp Ser Ser Phe Tyr Ile Cys Ser Ala Ala Gly Gln Ala Asn Thr Glu
115 120 125
Ala Phe Phe Gly Gln Gly Thr Arg Leu Thr Val Val Glu Asp Leu Arg
130 135 140
Asn Val Thr Pro Pro Lys Val Ser Leu Phe Glu Pro Ser Lys Ala Glu
145 150 155 160
Ile Ala Asn Lys Gln Lys Ala Thr Leu Val Cys Leu Ala Arg Gly Phe
165 170 175
Phe Pro Asp His Val Glu Leu Ser Trp Trp Val Asn Gly Lys Glu Val
180 185 190
His Ser Gly Val Cys Thr Asp Pro Gln Ala Tyr Lys Glu Ser Asn Tyr
195 200 205
Ser Tyr Cys Leu Ser Ser Arg Leu Arg Val Ser Ala Thr Phe Trp His
210 215 220
Asn Pro Arg Asn His Phe Arg Cys Gln Val Gln Phe His Gly Leu Ser
225 230 235 240
Glu Glu Asp Lys Trp Pro Glu Gly Ser Pro Lys Pro Val Thr Gln Asn
245 250 255
Ile Ser Ala Glu Ala Trp Gly Arg Ala Asp Cys Gly Ile Thr Ser Ala
260 265 270
Ser Tyr Gln Gln Gly Val Leu Ser Ala Thr Ile Leu Tyr Glu Ile Leu
275 280 285
Leu Gly Lys Ala Thr Leu Tyr Ala Val Leu Val Ser Thr Leu Val Val
290 295 300
Met Ala Met Val Lys Arg Lys Asn Ser
305 310
<210> 467
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 467
Asp Ser Ala Ser Asn Tyr
1 5
<210> 468
<211> 7
<212> PRT
<213> 智人(Homo sapiens)
<400> 468
Ile Arg Ser Asn Val Gly Glu
1 5
<210> 469
<211> 18
<212> PRT
<213> 智人(Homo sapiens)
<400> 469
Cys Ala Ala Ser Lys Ser Ala Ile Met Val Val Leu Gln Thr Ser Ser
1 5 10 15
Ser Leu
<210> 470
<211> 5
<212> PRT
<213> 智人(Homo sapiens)
<400> 470
Met Asn His Glu Tyr
1 5
<210> 471
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 471
Ser Met Asn Val Glu Val
1 5
<210> 472
<211> 14
<212> PRT
<213> 智人(Homo sapiens)
<400> 472
Cys Ala Ser Ser Ile Gln Gln Gly Ala Asp Thr Gln Tyr Phe
1 5 10
<210> 473
<211> 137
<212> PRT
<213> 智人(Homo sapiens)
<400> 473
Met Ala Ser Ile Arg Ala Val Phe Ile Phe Leu Trp Leu Gln Leu Asp
1 5 10 15
Leu Val Asn Gly Glu Asn Val Glu Gln His Pro Ser Thr Leu Ser Val
20 25 30
Gln Glu Gly Asp Ser Ala Val Ile Lys Cys Thr Tyr Ser Asp Ser Ala
35 40 45
Ser Asn Tyr Phe Pro Trp Tyr Lys Gln Glu Leu Gly Lys Gly Pro Gln
50 55 60
Leu Ile Ile Asp Ile Arg Ser Asn Val Gly Glu Lys Lys Asp Gln Arg
65 70 75 80
Ile Ala Val Thr Leu Asn Lys Thr Ala Lys His Phe Ser Leu His Ile
85 90 95
Thr Glu Thr Gln Pro Glu Asp Ser Ala Val Tyr Phe Cys Ala Ala Ser
100 105 110
Lys Ser Ala Ile Met Val Val Leu Gln Thr Ser Ser Ser Leu Glu Leu
115 120 125
Ala Leu Cys Leu Leu Ser Ser Gln Val
130 135
<210> 474
<211> 132
<212> PRT
<213> 智人(Homo sapiens)
<400> 474
Met His Pro Gln Leu Leu Gly Tyr Val Val Leu Cys Leu Leu Gly Ala
1 5 10 15
Gly Pro Leu Glu Ala Gln Val Thr Gln Asn Pro Arg Tyr Leu Ile Thr
20 25 30
Val Thr Gly Lys Lys Leu Thr Val Thr Cys Ser Gln Asn Met Asn His
35 40 45
Glu Tyr Met Ser Trp Tyr Arg Gln Asp Pro Gly Leu Gly Leu Arg Gln
50 55 60
Ile Tyr Tyr Ser Met Asn Val Glu Val Thr Asp Lys Gly Asp Val Pro
65 70 75 80
Glu Gly Tyr Lys Val Ser Arg Lys Glu Lys Arg Asn Phe Pro Leu Ile
85 90 95
Leu Glu Ser Pro Ser Pro Asn Gln Thr Ser Leu Tyr Phe Cys Ala Ser
100 105 110
Ser Ile Gln Gln Gly Ala Asp Thr Gln Tyr Phe Gly Pro Gly Thr Arg
115 120 125
Leu Thr Val Leu
130
<210> 475
<211> 274
<212> PRT
<213> 智人(Homo sapiens)
<400> 475
Met Ala Ser Ile Arg Ala Val Phe Ile Phe Leu Trp Leu Gln Leu Asp
1 5 10 15
Leu Val Asn Gly Glu Asn Val Glu Gln His Pro Ser Thr Leu Ser Val
20 25 30
Gln Glu Gly Asp Ser Ala Val Ile Lys Cys Thr Tyr Ser Asp Ser Ala
35 40 45
Ser Asn Tyr Phe Pro Trp Tyr Lys Gln Glu Leu Gly Lys Gly Pro Gln
50 55 60
Leu Ile Ile Asp Ile Arg Ser Asn Val Gly Glu Lys Lys Asp Gln Arg
65 70 75 80
Ile Ala Val Thr Leu Asn Lys Thr Ala Lys His Phe Ser Leu His Ile
85 90 95
Thr Glu Thr Gln Pro Glu Asp Ser Ala Val Tyr Phe Cys Ala Ala Ser
100 105 110
Lys Ser Ala Ile Met Val Val Leu Gln Thr Ser Ser Ser Leu Glu Leu
115 120 125
Ala Leu Cys Leu Leu Ser Ser Gln Val Asn Ile Gln Asn Pro Glu Pro
130 135 140
Ala Val Tyr Gln Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys
145 150 155 160
Leu Phe Thr Asp Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu
165 170 175
Ser Gly Thr Phe Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met
180 185 190
Asp Ser Lys Ser Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe
195 200 205
Thr Cys Gln Asp Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser
210 215 220
Asp Val Pro Cys Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp
225 230 235 240
Met Asn Leu Asn Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu
245 250 255
Leu Leu Lys Val Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp
260 265 270
Ser Ser
<210> 476
<211> 305
<212> PRT
<213> 智人(Homo sapiens)
<400> 476
Met His Pro Gln Leu Leu Gly Tyr Val Val Leu Cys Leu Leu Gly Ala
1 5 10 15
Gly Pro Leu Glu Ala Gln Val Thr Gln Asn Pro Arg Tyr Leu Ile Thr
20 25 30
Val Thr Gly Lys Lys Leu Thr Val Thr Cys Ser Gln Asn Met Asn His
35 40 45
Glu Tyr Met Ser Trp Tyr Arg Gln Asp Pro Gly Leu Gly Leu Arg Gln
50 55 60
Ile Tyr Tyr Ser Met Asn Val Glu Val Thr Asp Lys Gly Asp Val Pro
65 70 75 80
Glu Gly Tyr Lys Val Ser Arg Lys Glu Lys Arg Asn Phe Pro Leu Ile
85 90 95
Leu Glu Ser Pro Ser Pro Asn Gln Thr Ser Leu Tyr Phe Cys Ala Ser
100 105 110
Ser Ile Gln Gln Gly Ala Asp Thr Gln Tyr Phe Gly Pro Gly Thr Arg
115 120 125
Leu Thr Val Leu Glu Asp Leu Arg Asn Val Thr Pro Pro Lys Val Ser
130 135 140
Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys Ala Thr
145 150 155 160
Leu Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu Leu Ser
165 170 175
Trp Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr Asp Pro
180 185 190
Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser Arg Leu
195 200 205
Arg Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe Arg Cys
210 215 220
Gln Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro Glu Gly
225 230 235 240
Ser Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp Gly Arg
245 250 255
Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val Leu Ser
260 265 270
Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu Tyr Ala
275 280 285
Val Leu Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg Lys Asn
290 295 300
Ser
305
<210> 477
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 477
Asp Arg Gly Ser Gln Ser
1 5
<210> 478
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 478
Ile Tyr Ser Asn Gly Asp
1 5
<210> 479
<211> 14
<212> PRT
<213> 智人(Homo sapiens)
<400> 479
Cys Ala Trp Asn Ser Gly Gly Ser Asn Tyr Lys Leu Thr Phe
1 5 10
<210> 480
<211> 5
<212> PRT
<213> 智人(Homo sapiens)
<400> 480
Met Asn His Glu Tyr
1 5
<210> 481
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 481
Ser Val Gly Glu Gly Thr
1 5
<210> 482
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 482
Cys Ala Ser Ser Tyr Ser Gln Ala Trp Gly Gln Pro Gln His Phe
1 5 10 15
<210> 483
<211> 133
<212> PRT
<213> 智人(Homo sapiens)
<400> 483
Met Ala Ser Leu Arg Val Leu Leu Val Ile Leu Trp Leu Gln Leu Ser
1 5 10 15
Trp Val Trp Ser Gln Gln Lys Glu Val Glu Gln Asn Ser Gly Pro Leu
20 25 30
Ser Val Pro Glu Gly Ala Ile Ala Ser Leu Asn Cys Thr Tyr Ser Asp
35 40 45
Arg Gly Ser Gln Ser Phe Phe Trp Tyr Arg Gln Tyr Ser Gly Lys Ser
50 55 60
Pro Glu Leu Ile Met Phe Ile Tyr Ser Asn Gly Asp Lys Glu Asp Gly
65 70 75 80
Arg Phe Thr Ala Gln Leu Asn Lys Ala Ser Gln Tyr Val Ser Leu Leu
85 90 95
Ile Arg Asp Ser Gln Pro Ser Asp Ser Ala Thr Tyr Leu Cys Ala Trp
100 105 110
Asn Ser Gly Gly Ser Asn Tyr Lys Leu Thr Phe Gly Lys Gly Thr Leu
115 120 125
Leu Thr Val Asn Pro
130
<210> 484
<211> 133
<212> PRT
<213> 智人(Homo sapiens)
<400> 484
Met His Leu Gly Leu Leu Cys Cys Gly Ala Phe Ser Leu Leu Trp Ala
1 5 10 15
Gly Pro Val Asn Ala Gly Val Thr Gln Thr Pro Lys Phe Arg Val Leu
20 25 30
Lys Thr Gly Gln Ser Met Thr Leu Leu Cys Ala Gln Asp Met Asn His
35 40 45
Glu Tyr Met Tyr Trp Tyr Arg Gln Asp Pro Gly Met Gly Leu Arg Leu
50 55 60
Ile His Tyr Ser Val Gly Glu Gly Thr Thr Ala Lys Gly Glu Val Pro
65 70 75 80
Asp Gly Tyr Asn Val Ser Arg Leu Lys Lys Gln Asn Phe Leu Leu Gly
85 90 95
Leu Glu Ser Ala Ala Pro Ser Gln Thr Ser Val Tyr Phe Cys Ala Ser
100 105 110
Ser Tyr Ser Gln Ala Trp Gly Gln Pro Gln His Phe Gly Asp Gly Thr
115 120 125
Arg Leu Ser Ile Leu
130
<210> 485
<211> 270
<212> PRT
<213> 智人(Homo sapiens)
<400> 485
Met Ala Ser Leu Arg Val Leu Leu Val Ile Leu Trp Leu Gln Leu Ser
1 5 10 15
Trp Val Trp Ser Gln Gln Lys Glu Val Glu Gln Asn Ser Gly Pro Leu
20 25 30
Ser Val Pro Glu Gly Ala Ile Ala Ser Leu Asn Cys Thr Tyr Ser Asp
35 40 45
Arg Gly Ser Gln Ser Phe Phe Trp Tyr Arg Gln Tyr Ser Gly Lys Ser
50 55 60
Pro Glu Leu Ile Met Phe Ile Tyr Ser Asn Gly Asp Lys Glu Asp Gly
65 70 75 80
Arg Phe Thr Ala Gln Leu Asn Lys Ala Ser Gln Tyr Val Ser Leu Leu
85 90 95
Ile Arg Asp Ser Gln Pro Ser Asp Ser Ala Thr Tyr Leu Cys Ala Trp
100 105 110
Asn Ser Gly Gly Ser Asn Tyr Lys Leu Thr Phe Gly Lys Gly Thr Leu
115 120 125
Leu Thr Val Asn Pro Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr Gln
130 135 140
Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr Asp
145 150 155 160
Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr Phe
165 170 175
Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys Ser
180 185 190
Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln Asp
195 200 205
Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro Cys
210 215 220
Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu Asn
225 230 235 240
Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys Val
245 250 255
Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser
260 265 270
<210> 486
<211> 306
<212> PRT
<213> 智人(Homo sapiens)
<400> 486
Met His Leu Gly Leu Leu Cys Cys Gly Ala Phe Ser Leu Leu Trp Ala
1 5 10 15
Gly Pro Val Asn Ala Gly Val Thr Gln Thr Pro Lys Phe Arg Val Leu
20 25 30
Lys Thr Gly Gln Ser Met Thr Leu Leu Cys Ala Gln Asp Met Asn His
35 40 45
Glu Tyr Met Tyr Trp Tyr Arg Gln Asp Pro Gly Met Gly Leu Arg Leu
50 55 60
Ile His Tyr Ser Val Gly Glu Gly Thr Thr Ala Lys Gly Glu Val Pro
65 70 75 80
Asp Gly Tyr Asn Val Ser Arg Leu Lys Lys Gln Asn Phe Leu Leu Gly
85 90 95
Leu Glu Ser Ala Ala Pro Ser Gln Thr Ser Val Tyr Phe Cys Ala Ser
100 105 110
Ser Tyr Ser Gln Ala Trp Gly Gln Pro Gln His Phe Gly Asp Gly Thr
115 120 125
Arg Leu Ser Ile Leu Glu Asp Leu Arg Asn Val Thr Pro Pro Lys Val
130 135 140
Ser Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys Ala
145 150 155 160
Thr Leu Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu Leu
165 170 175
Ser Trp Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr Asp
180 185 190
Pro Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser Arg
195 200 205
Leu Arg Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe Arg
210 215 220
Cys Gln Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro Glu
225 230 235 240
Gly Ser Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp Gly
245 250 255
Arg Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val Leu
260 265 270
Ser Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu Tyr
275 280 285
Ala Val Leu Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg Lys
290 295 300
Asn Ser
305
<210> 487
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 487
Ser Ser Asn Phe Tyr Ala
1 5
<210> 488
<211> 7
<212> PRT
<213> 智人(Homo sapiens)
<400> 488
Met Thr Leu Asn Gly Asp Glu
1 5
<210> 489
<211> 13
<212> PRT
<213> 智人(Homo sapiens)
<400> 489
Cys Ala Leu Ile Thr Gly Gly Gly Asn Lys Leu Thr Phe
1 5 10
<210> 490
<211> 5
<212> PRT
<213> 智人(Homo sapiens)
<400> 490
Met Asn His Glu Tyr
1 5
<210> 491
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<400> 491
Ser Val Gly Glu Gly Thr
1 5
<210> 492
<211> 14
<212> PRT
<213> 智人(Homo sapiens)
<400> 492
Cys Ala Ser Arg Leu Gln Gly Trp Asn Ser Pro Leu His Phe
1 5 10
<210> 493
<211> 134
<212> PRT
<213> 智人(Homo sapiens)
<400> 493
Met Ala Lys Asn Pro Leu Ala Ala Pro Leu Leu Ile Leu Trp Phe His
1 5 10 15
Leu Asp Cys Val Ser Ser Ile Leu Asn Val Glu Gln Ser Pro Gln Ser
20 25 30
Leu His Val Gln Glu Gly Asp Ser Thr Asn Phe Thr Cys Ser Phe Pro
35 40 45
Ser Ser Asn Phe Tyr Ala Leu His Trp Tyr Arg Trp Glu Thr Ala Lys
50 55 60
Ser Pro Glu Ala Leu Phe Val Met Thr Leu Asn Gly Asp Glu Lys Lys
65 70 75 80
Lys Gly Arg Ile Ser Ala Thr Leu Asn Thr Lys Glu Gly Tyr Ser Tyr
85 90 95
Leu Tyr Ile Lys Gly Ser Gln Pro Glu Asp Ser Ala Thr Tyr Leu Cys
100 105 110
Ala Leu Ile Thr Gly Gly Gly Asn Lys Leu Thr Phe Gly Thr Gly Thr
115 120 125
Gln Leu Lys Val Glu Leu
130
<210> 494
<211> 132
<212> PRT
<213> 智人(Homo sapiens)
<400> 494
Met His Leu Gly Leu Leu Cys Cys Gly Ala Phe Ser Leu Leu Trp Ala
1 5 10 15
Gly Pro Val Asn Ala Gly Val Thr Gln Thr Pro Lys Phe Arg Val Leu
20 25 30
Lys Thr Gly Gln Ser Met Thr Leu Leu Cys Ala Gln Asp Met Asn His
35 40 45
Glu Tyr Met Tyr Trp Tyr Arg Gln Asp Pro Gly Met Gly Leu Arg Leu
50 55 60
Ile His Tyr Ser Val Gly Glu Gly Thr Thr Ala Lys Gly Glu Val Pro
65 70 75 80
Asp Gly Tyr Asn Val Ser Arg Leu Lys Lys Gln Asn Phe Leu Leu Gly
85 90 95
Leu Glu Ser Ala Ala Pro Ser Gln Thr Ser Val Tyr Phe Cys Ala Ser
100 105 110
Arg Leu Gln Gly Trp Asn Ser Pro Leu His Phe Gly Asn Gly Thr Arg
115 120 125
Leu Thr Val Thr
130
<210> 495
<211> 271
<212> PRT
<213> 智人(Homo sapiens)
<400> 495
Met Ala Lys Asn Pro Leu Ala Ala Pro Leu Leu Ile Leu Trp Phe His
1 5 10 15
Leu Asp Cys Val Ser Ser Ile Leu Asn Val Glu Gln Ser Pro Gln Ser
20 25 30
Leu His Val Gln Glu Gly Asp Ser Thr Asn Phe Thr Cys Ser Phe Pro
35 40 45
Ser Ser Asn Phe Tyr Ala Leu His Trp Tyr Arg Trp Glu Thr Ala Lys
50 55 60
Ser Pro Glu Ala Leu Phe Val Met Thr Leu Asn Gly Asp Glu Lys Lys
65 70 75 80
Lys Gly Arg Ile Ser Ala Thr Leu Asn Thr Lys Glu Gly Tyr Ser Tyr
85 90 95
Leu Tyr Ile Lys Gly Ser Gln Pro Glu Asp Ser Ala Thr Tyr Leu Cys
100 105 110
Ala Leu Ile Thr Gly Gly Gly Asn Lys Leu Thr Phe Gly Thr Gly Thr
115 120 125
Gln Leu Lys Val Glu Leu Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr
130 135 140
Gln Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr
145 150 155 160
Asp Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr
165 170 175
Phe Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys
180 185 190
Ser Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln
195 200 205
Asp Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro
210 215 220
Cys Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu
225 230 235 240
Asn Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys
245 250 255
Val Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser
260 265 270
<210> 496
<211> 305
<212> PRT
<213> 智人(Homo sapiens)
<400> 496
Met His Leu Gly Leu Leu Cys Cys Gly Ala Phe Ser Leu Leu Trp Ala
1 5 10 15
Gly Pro Val Asn Ala Gly Val Thr Gln Thr Pro Lys Phe Arg Val Leu
20 25 30
Lys Thr Gly Gln Ser Met Thr Leu Leu Cys Ala Gln Asp Met Asn His
35 40 45
Glu Tyr Met Tyr Trp Tyr Arg Gln Asp Pro Gly Met Gly Leu Arg Leu
50 55 60
Ile His Tyr Ser Val Gly Glu Gly Thr Thr Ala Lys Gly Glu Val Pro
65 70 75 80
Asp Gly Tyr Asn Val Ser Arg Leu Lys Lys Gln Asn Phe Leu Leu Gly
85 90 95
Leu Glu Ser Ala Ala Pro Ser Gln Thr Ser Val Tyr Phe Cys Ala Ser
100 105 110
Arg Leu Gln Gly Trp Asn Ser Pro Leu His Phe Gly Asn Gly Thr Arg
115 120 125
Leu Thr Val Thr Glu Asp Leu Arg Asn Val Thr Pro Pro Lys Val Ser
130 135 140
Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys Ala Thr
145 150 155 160
Leu Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu Leu Ser
165 170 175
Trp Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr Asp Pro
180 185 190
Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser Arg Leu
195 200 205
Arg Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe Arg Cys
210 215 220
Gln Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro Glu Gly
225 230 235 240
Ser Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp Gly Arg
245 250 255
Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val Leu Ser
260 265 270
Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu Tyr Ala
275 280 285
Val Leu Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg Lys Asn
290 295 300
Ser
305
<210> 497
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 497
His Tyr Asn Tyr Met Cys Asn Ser Ser Cys Met Gly Ser Met Asn
1 5 10 15
<210> 498
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 498
Tyr Asn Tyr Met Cys Asn Ser Ser Cys Met Gly Ser Met Asn Arg
1 5 10 15
<210> 499
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 499
Asn Tyr Met Cys Asn Ser Ser Cys Met Gly Ser Met Asn Arg Arg
1 5 10 15
<210> 500
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 500
Tyr Met Cys Asn Ser Ser Cys Met Gly Ser Met Asn Arg Arg Pro
1 5 10 15
<210> 501
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 501
Met Cys Asn Ser Ser Cys Met Gly Ser Met Asn Arg Arg Pro Ile
1 5 10 15
<210> 502
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 502
Cys Asn Ser Ser Cys Met Gly Ser Met Asn Arg Arg Pro Ile Leu
1 5 10 15
<210> 503
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 503
Asn Ser Ser Cys Met Gly Ser Met Asn Arg Arg Pro Ile Leu Thr
1 5 10 15
<210> 504
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 504
Ser Ser Cys Met Gly Ser Met Asn Arg Arg Pro Ile Leu Thr Ile
1 5 10 15
<210> 505
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 505
Ser Cys Met Gly Ser Met Asn Arg Arg Pro Ile Leu Thr Ile Ile
1 5 10 15
<210> 506
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 506
Cys Met Gly Ser Met Asn Arg Arg Pro Ile Leu Thr Ile Ile Thr
1 5 10 15
<210> 507
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 507
Met Gly Ser Met Asn Arg Arg Pro Ile Leu Thr Ile Ile Thr Leu
1 5 10 15
<210> 508
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 508
Asp Arg Asn Thr Phe Arg His Ser Val Val Val Pro Cys Glu Pro
1 5 10 15
<210> 509
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 509
Arg Asn Thr Phe Arg His Ser Val Val Val Pro Cys Glu Pro Pro
1 5 10 15
<210> 510
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 510
Asn Thr Phe Arg His Ser Val Val Val Pro Cys Glu Pro Pro Glu
1 5 10 15
<210> 511
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 511
Thr Phe Arg His Ser Val Val Val Pro Cys Glu Pro Pro Glu Val
1 5 10 15
<210> 512
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 512
Phe Arg His Ser Val Val Val Pro Cys Glu Pro Pro Glu Val Gly
1 5 10 15
<210> 513
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 513
Arg His Ser Val Val Val Pro Cys Glu Pro Pro Glu Val Gly Ser
1 5 10 15
<210> 514
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 514
His Ser Val Val Val Pro Cys Glu Pro Pro Glu Val Gly Ser Asp
1 5 10 15
<210> 515
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 515
Ser Val Val Val Pro Cys Glu Pro Pro Glu Val Gly Ser Asp Cys
1 5 10 15
<210> 516
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 516
Val Val Val Pro Cys Glu Pro Pro Glu Val Gly Ser Asp Cys Thr
1 5 10 15
<210> 517
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 517
Val Val Pro Cys Glu Pro Pro Glu Val Gly Ser Asp Cys Thr Thr
1 5 10 15
<210> 518
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 518
Val Pro Cys Glu Pro Pro Glu Val Gly Ser Asp Cys Thr Thr Ile
1 5 10 15
<210> 519
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 519
Tyr Lys Gln Ser Gln His Met Thr Glu Val Val Arg His Cys Pro
1 5 10 15
<210> 520
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 520
Lys Gln Ser Gln His Met Thr Glu Val Val Arg His Cys Pro His
1 5 10 15
<210> 521
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 521
Gln Ser Gln His Met Thr Glu Val Val Arg His Cys Pro His His
1 5 10 15
<210> 522
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 522
Ser Gln His Met Thr Glu Val Val Arg His Cys Pro His His Glu
1 5 10 15
<210> 523
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 523
Gln His Met Thr Glu Val Val Arg His Cys Pro His His Glu Arg
1 5 10 15
<210> 524
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 524
His Met Thr Glu Val Val Arg His Cys Pro His His Glu Arg Cys
1 5 10 15
<210> 525
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 525
Met Thr Glu Val Val Arg His Cys Pro His His Glu Arg Cys Ser
1 5 10 15
<210> 526
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 526
Thr Glu Val Val Arg His Cys Pro His His Glu Arg Cys Ser Asp
1 5 10 15
<210> 527
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 527
Glu Val Val Arg His Cys Pro His His Glu Arg Cys Ser Asp Ser
1 5 10 15
<210> 528
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 528
Val Val Arg His Cys Pro His His Glu Arg Cys Ser Asp Ser Asp
1 5 10 15
<210> 529
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 529
Val Arg His Cys Pro His His Glu Arg Cys Ser Asp Ser Asp Gly
1 5 10 15
<210> 530
<211> 9
<212> PRT
<213> 智人(Homo sapiens)
<400> 530
His Met Thr Glu Val Val Arg His Cys
1 5
<210> 531
<211> 10
<212> PRT
<213> 智人(Homo sapiens)
<400> 531
Ser Gln His Met Thr Glu Val Val Arg His
1 5 10
<210> 532
<211> 9
<212> PRT
<213> 智人(Homo sapiens)
<400> 532
His Met Thr Glu Val Val Arg Arg Cys
1 5
<210> 533
<211> 13
<212> PRT
<213> 智人(Homo sapiens)
<400> 533
Arg Asn Thr Phe Arg His Ser Val Val Val Pro Tyr Glu
1 5 10
<210> 534
<211> 13
<212> PRT
<213> 智人(Homo sapiens)
<400> 534
Arg Asn Thr Phe Arg His Ser Val Val Val Pro Cys Glu
1 5 10
<210> 535
<211> 341
<212> PRT
<213> 智人(Homo sapiens)
<400> 535
Met Glu Glu Pro Gln Ser Asp Pro Ser Val Glu Pro Pro Leu Ser Gln
1 5 10 15
Glu Thr Phe Ser Asp Leu Trp Lys Leu Leu Pro Glu Asn Asn Val Leu
20 25 30
Ser Pro Leu Pro Ser Gln Ala Met Asp Asp Leu Met Leu Ser Pro Asp
35 40 45
Asp Ile Glu Gln Trp Phe Thr Glu Asp Pro Gly Pro Asp Glu Ala Pro
50 55 60
Arg Met Pro Glu Ala Ala Pro Pro Val Ala Pro Ala Pro Ala Ala Pro
65 70 75 80
Thr Pro Ala Ala Pro Ala Pro Ala Pro Ser Trp Pro Leu Ser Ser Ser
85 90 95
Val Pro Ser Gln Lys Thr Tyr Gln Gly Ser Tyr Gly Phe Arg Leu Gly
100 105 110
Phe Leu His Ser Gly Thr Ala Lys Ser Val Thr Cys Thr Tyr Ser Pro
115 120 125
Ala Leu Asn Lys Met Phe Cys Gln Leu Ala Lys Thr Cys Pro Val Gln
130 135 140
Leu Trp Val Asp Ser Thr Pro Pro Pro Gly Thr Arg Val Arg Ala Met
145 150 155 160
Ala Ile Tyr Lys Gln Ser Gln His Met Thr Glu Val Val Arg Arg Cys
165 170 175
Pro His His Glu Arg Cys Ser Asp Ser Asp Gly Leu Ala Pro Pro Gln
180 185 190
His Leu Ile Arg Val Glu Gly Asn Leu Arg Val Glu Tyr Leu Asp Asp
195 200 205
Arg Asn Thr Phe Arg His Ser Val Val Val Pro Tyr Glu Pro Pro Glu
210 215 220
Val Gly Ser Asp Cys Thr Thr Ile His Tyr Asn Tyr Met Cys Asn Ser
225 230 235 240
Ser Cys Met Gly Gly Met Asn Arg Arg Pro Ile Leu Thr Ile Ile Thr
245 250 255
Leu Glu Asp Ser Ser Gly Asn Leu Leu Gly Arg Asn Ser Phe Glu Val
260 265 270
Arg Val Cys Ala Cys Pro Gly Arg Asp Arg Arg Thr Glu Glu Glu Asn
275 280 285
Leu Arg Lys Lys Gly Glu Pro His His Glu Leu Pro Pro Gly Ser Thr
290 295 300
Lys Arg Ala Leu Pro Asn Asn Thr Ser Ser Ser Pro Gln Pro Lys Lys
305 310 315 320
Lys Pro Leu Asp Gly Glu Tyr Phe Thr Leu Gln Asp Gln Thr Ser Phe
325 330 335
Gln Lys Glu Asn Cys
340
<210> 536
<211> 346
<212> PRT
<213> 智人(Homo sapiens)
<400> 536
Met Glu Glu Pro Gln Ser Asp Pro Ser Val Glu Pro Pro Leu Ser Gln
1 5 10 15
Glu Thr Phe Ser Asp Leu Trp Lys Leu Leu Pro Glu Asn Asn Val Leu
20 25 30
Ser Pro Leu Pro Ser Gln Ala Met Asp Asp Leu Met Leu Ser Pro Asp
35 40 45
Asp Ile Glu Gln Trp Phe Thr Glu Asp Pro Gly Pro Asp Glu Ala Pro
50 55 60
Arg Met Pro Glu Ala Ala Pro Pro Val Ala Pro Ala Pro Ala Ala Pro
65 70 75 80
Thr Pro Ala Ala Pro Ala Pro Ala Pro Ser Trp Pro Leu Ser Ser Ser
85 90 95
Val Pro Ser Gln Lys Thr Tyr Gln Gly Ser Tyr Gly Phe Arg Leu Gly
100 105 110
Phe Leu His Ser Gly Thr Ala Lys Ser Val Thr Cys Thr Tyr Ser Pro
115 120 125
Ala Leu Asn Lys Met Phe Cys Gln Leu Ala Lys Thr Cys Pro Val Gln
130 135 140
Leu Trp Val Asp Ser Thr Pro Pro Pro Gly Thr Arg Val Arg Ala Met
145 150 155 160
Ala Ile Tyr Lys Gln Ser Gln His Met Thr Glu Val Val Arg Arg Cys
165 170 175
Pro His His Glu Arg Cys Ser Asp Ser Asp Gly Leu Ala Pro Pro Gln
180 185 190
His Leu Ile Arg Val Glu Gly Asn Leu Arg Val Glu Tyr Leu Asp Asp
195 200 205
Arg Asn Thr Phe Arg His Ser Val Val Val Pro Tyr Glu Pro Pro Glu
210 215 220
Val Gly Ser Asp Cys Thr Thr Ile His Tyr Asn Tyr Met Cys Asn Ser
225 230 235 240
Ser Cys Met Gly Gly Met Asn Arg Arg Pro Ile Leu Thr Ile Ile Thr
245 250 255
Leu Glu Asp Ser Ser Gly Asn Leu Leu Gly Arg Asn Ser Phe Glu Val
260 265 270
Arg Val Cys Ala Cys Pro Gly Arg Asp Arg Arg Thr Glu Glu Glu Asn
275 280 285
Leu Arg Lys Lys Gly Glu Pro His His Glu Leu Pro Pro Gly Ser Thr
290 295 300
Lys Arg Ala Leu Pro Asn Asn Thr Ser Ser Ser Pro Gln Pro Lys Lys
305 310 315 320
Lys Pro Leu Asp Gly Glu Tyr Phe Thr Leu Gln Met Leu Leu Asp Leu
325 330 335
Arg Trp Cys Tyr Phe Leu Ile Asn Ser Ser
340 345
<210> 537
<211> 354
<212> PRT
<213> 智人(Homo sapiens)
<400> 537
Met Asp Asp Leu Met Leu Ser Pro Asp Asp Ile Glu Gln Trp Phe Thr
1 5 10 15
Glu Asp Pro Gly Pro Asp Glu Ala Pro Arg Met Pro Glu Ala Ala Pro
20 25 30
Pro Val Ala Pro Ala Pro Ala Ala Pro Thr Pro Ala Ala Pro Ala Pro
35 40 45
Ala Pro Ser Trp Pro Leu Ser Ser Ser Val Pro Ser Gln Lys Thr Tyr
50 55 60
Gln Gly Ser Tyr Gly Phe Arg Leu Gly Phe Leu His Ser Gly Thr Ala
65 70 75 80
Lys Ser Val Thr Cys Thr Tyr Ser Pro Ala Leu Asn Lys Met Phe Cys
85 90 95
Gln Leu Ala Lys Thr Cys Pro Val Gln Leu Trp Val Asp Ser Thr Pro
100 105 110
Pro Pro Gly Thr Arg Val Arg Ala Met Ala Ile Tyr Lys Gln Ser Gln
115 120 125
His Met Thr Glu Val Val Arg Arg Cys Pro His His Glu Arg Cys Ser
130 135 140
Asp Ser Asp Gly Leu Ala Pro Pro Gln His Leu Ile Arg Val Glu Gly
145 150 155 160
Asn Leu Arg Val Glu Tyr Leu Asp Asp Arg Asn Thr Phe Arg His Ser
165 170 175
Val Val Val Pro Tyr Glu Pro Pro Glu Val Gly Ser Asp Cys Thr Thr
180 185 190
Ile His Tyr Asn Tyr Met Cys Asn Ser Ser Cys Met Gly Gly Met Asn
195 200 205
Arg Arg Pro Ile Leu Thr Ile Ile Thr Leu Glu Asp Ser Ser Gly Asn
210 215 220
Leu Leu Gly Arg Asn Ser Phe Glu Val Arg Val Cys Ala Cys Pro Gly
225 230 235 240
Arg Asp Arg Arg Thr Glu Glu Glu Asn Leu Arg Lys Lys Gly Glu Pro
245 250 255
His His Glu Leu Pro Pro Gly Ser Thr Lys Arg Ala Leu Pro Asn Asn
260 265 270
Thr Ser Ser Ser Pro Gln Pro Lys Lys Lys Pro Leu Asp Gly Glu Tyr
275 280 285
Phe Thr Leu Gln Ile Arg Gly Arg Glu Arg Phe Glu Met Phe Arg Glu
290 295 300
Leu Asn Glu Ala Leu Glu Leu Lys Asp Ala Gln Ala Gly Lys Glu Pro
305 310 315 320
Gly Gly Ser Arg Ala His Ser Ser His Leu Lys Ser Lys Lys Gly Gln
325 330 335
Ser Thr Ser Arg His Lys Lys Leu Met Phe Lys Thr Glu Gly Pro Asp
340 345 350
Ser Asp
<210> 538
<211> 302
<212> PRT
<213> 智人(Homo sapiens)
<400> 538
Met Asp Asp Leu Met Leu Ser Pro Asp Asp Ile Glu Gln Trp Phe Thr
1 5 10 15
Glu Asp Pro Gly Pro Asp Glu Ala Pro Arg Met Pro Glu Ala Ala Pro
20 25 30
Pro Val Ala Pro Ala Pro Ala Ala Pro Thr Pro Ala Ala Pro Ala Pro
35 40 45
Ala Pro Ser Trp Pro Leu Ser Ser Ser Val Pro Ser Gln Lys Thr Tyr
50 55 60
Gln Gly Ser Tyr Gly Phe Arg Leu Gly Phe Leu His Ser Gly Thr Ala
65 70 75 80
Lys Ser Val Thr Cys Thr Tyr Ser Pro Ala Leu Asn Lys Met Phe Cys
85 90 95
Gln Leu Ala Lys Thr Cys Pro Val Gln Leu Trp Val Asp Ser Thr Pro
100 105 110
Pro Pro Gly Thr Arg Val Arg Ala Met Ala Ile Tyr Lys Gln Ser Gln
115 120 125
His Met Thr Glu Val Val Arg Arg Cys Pro His His Glu Arg Cys Ser
130 135 140
Asp Ser Asp Gly Leu Ala Pro Pro Gln His Leu Ile Arg Val Glu Gly
145 150 155 160
Asn Leu Arg Val Glu Tyr Leu Asp Asp Arg Asn Thr Phe Arg His Ser
165 170 175
Val Val Val Pro Tyr Glu Pro Pro Glu Val Gly Ser Asp Cys Thr Thr
180 185 190
Ile His Tyr Asn Tyr Met Cys Asn Ser Ser Cys Met Gly Gly Met Asn
195 200 205
Arg Arg Pro Ile Leu Thr Ile Ile Thr Leu Glu Asp Ser Ser Gly Asn
210 215 220
Leu Leu Gly Arg Asn Ser Phe Glu Val Arg Val Cys Ala Cys Pro Gly
225 230 235 240
Arg Asp Arg Arg Thr Glu Glu Glu Asn Leu Arg Lys Lys Gly Glu Pro
245 250 255
His His Glu Leu Pro Pro Gly Ser Thr Lys Arg Ala Leu Pro Asn Asn
260 265 270
Thr Ser Ser Ser Pro Gln Pro Lys Lys Lys Pro Leu Asp Gly Glu Tyr
275 280 285
Phe Thr Leu Gln Asp Gln Thr Ser Phe Gln Lys Glu Asn Cys
290 295 300
<210> 539
<211> 307
<212> PRT
<213> 智人(Homo sapiens)
<400> 539
Met Asp Asp Leu Met Leu Ser Pro Asp Asp Ile Glu Gln Trp Phe Thr
1 5 10 15
Glu Asp Pro Gly Pro Asp Glu Ala Pro Arg Met Pro Glu Ala Ala Pro
20 25 30
Pro Val Ala Pro Ala Pro Ala Ala Pro Thr Pro Ala Ala Pro Ala Pro
35 40 45
Ala Pro Ser Trp Pro Leu Ser Ser Ser Val Pro Ser Gln Lys Thr Tyr
50 55 60
Gln Gly Ser Tyr Gly Phe Arg Leu Gly Phe Leu His Ser Gly Thr Ala
65 70 75 80
Lys Ser Val Thr Cys Thr Tyr Ser Pro Ala Leu Asn Lys Met Phe Cys
85 90 95
Gln Leu Ala Lys Thr Cys Pro Val Gln Leu Trp Val Asp Ser Thr Pro
100 105 110
Pro Pro Gly Thr Arg Val Arg Ala Met Ala Ile Tyr Lys Gln Ser Gln
115 120 125
His Met Thr Glu Val Val Arg Arg Cys Pro His His Glu Arg Cys Ser
130 135 140
Asp Ser Asp Gly Leu Ala Pro Pro Gln His Leu Ile Arg Val Glu Gly
145 150 155 160
Asn Leu Arg Val Glu Tyr Leu Asp Asp Arg Asn Thr Phe Arg His Ser
165 170 175
Val Val Val Pro Tyr Glu Pro Pro Glu Val Gly Ser Asp Cys Thr Thr
180 185 190
Ile His Tyr Asn Tyr Met Cys Asn Ser Ser Cys Met Gly Gly Met Asn
195 200 205
Arg Arg Pro Ile Leu Thr Ile Ile Thr Leu Glu Asp Ser Ser Gly Asn
210 215 220
Leu Leu Gly Arg Asn Ser Phe Glu Val Arg Val Cys Ala Cys Pro Gly
225 230 235 240
Arg Asp Arg Arg Thr Glu Glu Glu Asn Leu Arg Lys Lys Gly Glu Pro
245 250 255
His His Glu Leu Pro Pro Gly Ser Thr Lys Arg Ala Leu Pro Asn Asn
260 265 270
Thr Ser Ser Ser Pro Gln Pro Lys Lys Lys Pro Leu Asp Gly Glu Tyr
275 280 285
Phe Thr Leu Gln Met Leu Leu Asp Leu Arg Trp Cys Tyr Phe Leu Ile
290 295 300
Asn Ser Ser
305
<210> 540
<211> 261
<212> PRT
<213> 智人(Homo sapiens)
<400> 540
Met Phe Cys Gln Leu Ala Lys Thr Cys Pro Val Gln Leu Trp Val Asp
1 5 10 15
Ser Thr Pro Pro Pro Gly Thr Arg Val Arg Ala Met Ala Ile Tyr Lys
20 25 30
Gln Ser Gln His Met Thr Glu Val Val Arg Arg Cys Pro His His Glu
35 40 45
Arg Cys Ser Asp Ser Asp Gly Leu Ala Pro Pro Gln His Leu Ile Arg
50 55 60
Val Glu Gly Asn Leu Arg Val Glu Tyr Leu Asp Asp Arg Asn Thr Phe
65 70 75 80
Arg His Ser Val Val Val Pro Tyr Glu Pro Pro Glu Val Gly Ser Asp
85 90 95
Cys Thr Thr Ile His Tyr Asn Tyr Met Cys Asn Ser Ser Cys Met Gly
100 105 110
Gly Met Asn Arg Arg Pro Ile Leu Thr Ile Ile Thr Leu Glu Asp Ser
115 120 125
Ser Gly Asn Leu Leu Gly Arg Asn Ser Phe Glu Val Arg Val Cys Ala
130 135 140
Cys Pro Gly Arg Asp Arg Arg Thr Glu Glu Glu Asn Leu Arg Lys Lys
145 150 155 160
Gly Glu Pro His His Glu Leu Pro Pro Gly Ser Thr Lys Arg Ala Leu
165 170 175
Pro Asn Asn Thr Ser Ser Ser Pro Gln Pro Lys Lys Lys Pro Leu Asp
180 185 190
Gly Glu Tyr Phe Thr Leu Gln Ile Arg Gly Arg Glu Arg Phe Glu Met
195 200 205
Phe Arg Glu Leu Asn Glu Ala Leu Glu Leu Lys Asp Ala Gln Ala Gly
210 215 220
Lys Glu Pro Gly Gly Ser Arg Ala His Ser Ser His Leu Lys Ser Lys
225 230 235 240
Lys Gly Gln Ser Thr Ser Arg His Lys Lys Leu Met Phe Lys Thr Glu
245 250 255
Gly Pro Asp Ser Asp
260
<210> 541
<211> 209
<212> PRT
<213> 智人(Homo sapiens)
<400> 541
Met Phe Cys Gln Leu Ala Lys Thr Cys Pro Val Gln Leu Trp Val Asp
1 5 10 15
Ser Thr Pro Pro Pro Gly Thr Arg Val Arg Ala Met Ala Ile Tyr Lys
20 25 30
Gln Ser Gln His Met Thr Glu Val Val Arg Arg Cys Pro His His Glu
35 40 45
Arg Cys Ser Asp Ser Asp Gly Leu Ala Pro Pro Gln His Leu Ile Arg
50 55 60
Val Glu Gly Asn Leu Arg Val Glu Tyr Leu Asp Asp Arg Asn Thr Phe
65 70 75 80
Arg His Ser Val Val Val Pro Tyr Glu Pro Pro Glu Val Gly Ser Asp
85 90 95
Cys Thr Thr Ile His Tyr Asn Tyr Met Cys Asn Ser Ser Cys Met Gly
100 105 110
Gly Met Asn Arg Arg Pro Ile Leu Thr Ile Ile Thr Leu Glu Asp Ser
115 120 125
Ser Gly Asn Leu Leu Gly Arg Asn Ser Phe Glu Val Arg Val Cys Ala
130 135 140
Cys Pro Gly Arg Asp Arg Arg Thr Glu Glu Glu Asn Leu Arg Lys Lys
145 150 155 160
Gly Glu Pro His His Glu Leu Pro Pro Gly Ser Thr Lys Arg Ala Leu
165 170 175
Pro Asn Asn Thr Ser Ser Ser Pro Gln Pro Lys Lys Lys Pro Leu Asp
180 185 190
Gly Glu Tyr Phe Thr Leu Gln Asp Gln Thr Ser Phe Gln Lys Glu Asn
195 200 205
Cys
<210> 542
<211> 214
<212> PRT
<213> 智人(Homo sapiens)
<400> 542
Met Phe Cys Gln Leu Ala Lys Thr Cys Pro Val Gln Leu Trp Val Asp
1 5 10 15
Ser Thr Pro Pro Pro Gly Thr Arg Val Arg Ala Met Ala Ile Tyr Lys
20 25 30
Gln Ser Gln His Met Thr Glu Val Val Arg Arg Cys Pro His His Glu
35 40 45
Arg Cys Ser Asp Ser Asp Gly Leu Ala Pro Pro Gln His Leu Ile Arg
50 55 60
Val Glu Gly Asn Leu Arg Val Glu Tyr Leu Asp Asp Arg Asn Thr Phe
65 70 75 80
Arg His Ser Val Val Val Pro Tyr Glu Pro Pro Glu Val Gly Ser Asp
85 90 95
Cys Thr Thr Ile His Tyr Asn Tyr Met Cys Asn Ser Ser Cys Met Gly
100 105 110
Gly Met Asn Arg Arg Pro Ile Leu Thr Ile Ile Thr Leu Glu Asp Ser
115 120 125
Ser Gly Asn Leu Leu Gly Arg Asn Ser Phe Glu Val Arg Val Cys Ala
130 135 140
Cys Pro Gly Arg Asp Arg Arg Thr Glu Glu Glu Asn Leu Arg Lys Lys
145 150 155 160
Gly Glu Pro His His Glu Leu Pro Pro Gly Ser Thr Lys Arg Ala Leu
165 170 175
Pro Asn Asn Thr Ser Ser Ser Pro Gln Pro Lys Lys Lys Pro Leu Asp
180 185 190
Gly Glu Tyr Phe Thr Leu Gln Met Leu Leu Asp Leu Arg Trp Cys Tyr
195 200 205
Phe Leu Ile Asn Ser Ser
210
<210> 543
<211> 598
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 543
Met Ala Thr Arg Leu Leu Cys Trp Ala Ala Leu Cys Leu Leu Gly Ala
1 5 10 15
Glu Leu Thr Glu Ala Gly Val Ala Gln Ser Pro Arg Tyr Lys Ile Ile
20 25 30
Glu Lys Arg Gln Ser Val Ala Phe Trp Cys Asn Pro Ile Ser Gly His
35 40 45
Ala Thr Leu Tyr Trp Tyr Gln Gln Ile Leu Gly Gln Gly Pro Lys Leu
50 55 60
Leu Ile Gln Phe Gln Asn Asn Gly Val Val Asp Asp Ser Gln Leu Pro
65 70 75 80
Lys Asp Arg Phe Ser Ala Glu Arg Leu Lys Gly Val Asp Ser Thr Leu
85 90 95
Lys Ile Gln Pro Ala Lys Leu Glu Asp Ser Ala Val Tyr Leu Cys Ala
100 105 110
Ser Ser Leu Val Asn Thr Glu Ala Phe Phe Gly Gln Gly Thr Arg Leu
115 120 125
Thr Val Val Glu Asp Leu Arg Asn Val Thr Pro Pro Lys Val Ser Leu
130 135 140
Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys Ala Thr Leu
145 150 155 160
Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu Leu Ser Trp
165 170 175
Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr Asp Pro Gln
180 185 190
Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser Arg Leu Arg
195 200 205
Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe Arg Cys Gln
210 215 220
Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro Glu Gly Ser
225 230 235 240
Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp Gly Arg Ala
245 250 255
Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val Leu Ser Ala
260 265 270
Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu Tyr Ala Val
275 280 285
Leu Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg Lys Asn Ser
290 295 300
Arg Ala Lys Arg Ser Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys
305 310 315 320
Gln Ala Gly Asp Val Glu Glu Asn Pro Gly Pro Met Leu Leu Leu Leu
325 330 335
Ile Pro Val Leu Gly Met Ile Phe Ala Leu Arg Asp Ala Arg Ala Gln
340 345 350
Ser Val Ser Gln His Asn His His Val Ile Leu Ser Glu Ala Ala Ser
355 360 365
Leu Glu Leu Gly Cys Asn Tyr Ser Tyr Gly Gly Thr Val Asn Leu Phe
370 375 380
Trp Tyr Val Gln Tyr Pro Gly Gln His Leu Gln Leu Leu Leu Lys Tyr
385 390 395 400
Phe Ser Gly Asp Pro Leu Val Lys Gly Ile Lys Gly Phe Glu Ala Glu
405 410 415
Phe Ile Lys Ser Lys Phe Ser Phe Asn Leu Arg Lys Pro Ser Val Gln
420 425 430
Trp Ser Asp Thr Ala Glu Tyr Phe Cys Ala Val Lys Gly Asp Tyr Lys
435 440 445
Leu Ser Phe Gly Ala Gly Thr Thr Val Thr Val Arg Ala Asn Ile Gln
450 455 460
Asn Pro Glu Pro Ala Val Tyr Gln Leu Lys Asp Pro Arg Ser Gln Asp
465 470 475 480
Ser Thr Leu Cys Leu Phe Thr Asp Phe Asp Ser Gln Ile Asn Val Pro
485 490 495
Lys Thr Met Glu Ser Gly Thr Phe Ile Thr Asp Lys Cys Val Leu Asp
500 505 510
Met Lys Ala Met Asp Ser Lys Ser Asn Gly Ala Ile Ala Trp Ser Asn
515 520 525
Gln Thr Ser Phe Thr Cys Gln Asp Ile Phe Lys Glu Thr Asn Ala Thr
530 535 540
Tyr Pro Ser Ser Asp Val Pro Cys Asp Ala Thr Leu Thr Glu Lys Ser
545 550 555 560
Phe Glu Thr Asp Met Asn Leu Asn Phe Gln Asn Leu Leu Val Ile Val
565 570 575
Leu Arg Ile Leu Leu Leu Lys Val Ala Gly Phe Asn Leu Leu Met Thr
580 585 590
Leu Arg Leu Trp Ser Ser
595
<210> 544
<211> 604
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 544
Met Ala Pro Gly Leu Leu His Trp Met Ala Leu Cys Leu Leu Gly Thr
1 5 10 15
Gly His Gly Asp Ala Met Val Ile Gln Asn Pro Arg Tyr Gln Val Thr
20 25 30
Gln Phe Gly Lys Pro Val Thr Leu Ser Cys Ser Gln Thr Leu Asn His
35 40 45
Asn Val Met Tyr Trp Tyr Gln Gln Lys Ser Ser Gln Ala Pro Lys Leu
50 55 60
Leu Phe His Tyr Tyr Asp Lys Asp Phe Asn Asn Glu Ala Asp Thr Pro
65 70 75 80
Asp Asn Phe Gln Ser Arg Arg Pro Asn Thr Ser Phe Cys Phe Leu Asp
85 90 95
Ile Arg Ser Pro Gly Leu Gly Asp Ala Ala Met Tyr Leu Cys Ala Thr
100 105 110
Ser Arg Glu Leu Arg Gly Asn Glu Gln Phe Phe Gly Pro Gly Thr Arg
115 120 125
Leu Thr Val Leu Glu Asp Leu Arg Asn Val Thr Pro Pro Lys Val Ser
130 135 140
Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys Ala Thr
145 150 155 160
Leu Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu Leu Ser
165 170 175
Trp Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr Asp Pro
180 185 190
Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser Arg Leu
195 200 205
Arg Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe Arg Cys
210 215 220
Gln Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro Glu Gly
225 230 235 240
Ser Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp Gly Arg
245 250 255
Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val Leu Ser
260 265 270
Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu Tyr Ala
275 280 285
Val Leu Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg Lys Asn
290 295 300
Ser Arg Ala Lys Arg Ser Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu
305 310 315 320
Lys Gln Ala Gly Asp Val Glu Glu Asn Pro Gly Pro Met Leu Thr Ala
325 330 335
Ser Leu Leu Arg Ala Val Ile Ala Ser Ile Cys Val Val Ser Ser Met
340 345 350
Ala Gln Lys Val Thr Gln Ala Gln Thr Glu Ile Ser Val Val Glu Lys
355 360 365
Glu Asp Val Thr Leu Asp Cys Val Tyr Glu Thr Arg Asp Thr Thr Tyr
370 375 380
Tyr Leu Phe Trp Tyr Lys Gln Pro Pro Ser Gly Glu Leu Val Phe Leu
385 390 395 400
Ile Arg Arg Asn Ser Phe Asp Glu Gln Asn Glu Ile Ser Gly Arg Tyr
405 410 415
Ser Trp Asn Phe Gln Lys Ser Thr Ser Ser Phe Asn Phe Thr Ile Thr
420 425 430
Ala Ser Gln Val Val Asp Ser Ala Val Tyr Phe Cys Ala Leu Ser Glu
435 440 445
Gly Gly Ser Asn Tyr Lys Leu Thr Phe Gly Lys Gly Thr Leu Leu Thr
450 455 460
Val Asn Pro Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr Gln Leu Lys
465 470 475 480
Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr Asp Phe Asp
485 490 495
Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr Phe Ile Thr
500 505 510
Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys Ser Asn Gly
515 520 525
Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln Asp Ile Phe
530 535 540
Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro Cys Asp Ala
545 550 555 560
Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu Asn Phe Gln
565 570 575
Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys Val Ala Gly
580 585 590
Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser
595 600
<210> 545
<211> 598
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 545
Met Ala Met Ser Ile Gly Leu Leu Cys Cys Ala Ala Leu Ser Leu Leu
1 5 10 15
Trp Ala Gly Pro Val Asn Ala Gly Val Thr Gln Thr Pro Lys Phe Gln
20 25 30
Val Leu Lys Thr Gly Gln Ser Met Thr Leu Gln Cys Ala Gln Asp Met
35 40 45
Asn His Glu Tyr Met Ser Trp Tyr Arg Gln Asp Pro Gly Met Gly Leu
50 55 60
Arg Leu Ile His Tyr Ser Val Gly Ala Gly Ile Thr Asp Gln Gly Glu
65 70 75 80
Val Pro Asn Gly Tyr Asn Val Ser Arg Ser Thr Thr Glu Asp Phe Pro
85 90 95
Leu Arg Leu Leu Ser Ala Ala Pro Ser Gln Thr Ser Val Tyr Phe Cys
100 105 110
Ala Ser Ser Tyr Arg Glu Ser His Tyr Gly Tyr Thr Phe Gly Ser Gly
115 120 125
Thr Arg Leu Thr Val Val Glu Asp Leu Arg Asn Val Thr Pro Pro Lys
130 135 140
Val Ser Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys
145 150 155 160
Ala Thr Leu Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu
165 170 175
Leu Ser Trp Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr
180 185 190
Asp Pro Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser
195 200 205
Arg Leu Arg Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe
210 215 220
Arg Cys Gln Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro
225 230 235 240
Glu Gly Ser Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp
245 250 255
Gly Arg Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val
260 265 270
Leu Ser Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu
275 280 285
Tyr Ala Val Leu Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg
290 295 300
Lys Asn Ser Arg Ala Lys Arg Ser Gly Ser Gly Ala Thr Asn Phe Ser
305 310 315 320
Leu Leu Lys Gln Ala Gly Asp Val Glu Glu Asn Pro Gly Pro Met Trp
325 330 335
Gly Val Phe Leu Leu Tyr Val Ser Met Lys Met Gly Gly Thr Thr Gly
340 345 350
Gln Asn Ile Asp Gln Pro Thr Glu Met Thr Ala Thr Glu Gly Ala Ile
355 360 365
Val Gln Ile Asn Cys Thr Tyr Gln Thr Ser Gly Phe Asn Gly Leu Phe
370 375 380
Trp Tyr Gln Gln His Ala Gly Glu Ala Pro Thr Phe Leu Ser Tyr Asn
385 390 395 400
Val Leu Asp Gly Leu Glu Glu Lys Gly Arg Phe Ser Ser Phe Leu Ser
405 410 415
Arg Ser Lys Gly Tyr Ser Tyr Leu Leu Leu Lys Glu Leu Gln Met Lys
420 425 430
Asp Ser Ala Ser Tyr Leu Cys Ala Val Lys Trp Thr Gly Gly Phe Lys
435 440 445
Thr Ile Phe Gly Ala Gly Thr Arg Leu Phe Val Lys Ala Asn Ile Gln
450 455 460
Asn Pro Glu Pro Ala Val Tyr Gln Leu Lys Asp Pro Arg Ser Gln Asp
465 470 475 480
Ser Thr Leu Cys Leu Phe Thr Asp Phe Asp Ser Gln Ile Asn Val Pro
485 490 495
Lys Thr Met Glu Ser Gly Thr Phe Ile Thr Asp Lys Cys Val Leu Asp
500 505 510
Met Lys Ala Met Asp Ser Lys Ser Asn Gly Ala Ile Ala Trp Ser Asn
515 520 525
Gln Thr Ser Phe Thr Cys Gln Asp Ile Phe Lys Glu Thr Asn Ala Thr
530 535 540
Tyr Pro Ser Ser Asp Val Pro Cys Asp Ala Thr Leu Thr Glu Lys Ser
545 550 555 560
Phe Glu Thr Asp Met Asn Leu Asn Phe Gln Asn Leu Leu Val Ile Val
565 570 575
Leu Arg Ile Leu Leu Leu Lys Val Ala Gly Phe Asn Leu Leu Met Thr
580 585 590
Leu Arg Leu Trp Ser Ser
595
<210> 546
<211> 608
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 546
Met Ala Leu Leu Leu Leu Leu Leu Gly Pro Gly Ile Ser Leu Leu Leu
1 5 10 15
Pro Gly Ser Leu Ala Gly Ser Gly Leu Gly Ala Val Val Ser Gln His
20 25 30
Pro Ser Trp Val Ile Cys Lys Ser Gly Thr Ser Val Lys Ile Glu Cys
35 40 45
Arg Ser Leu Asp Phe Gln Ala Thr Thr Met Phe Trp Tyr Arg Gln Phe
50 55 60
Pro Lys Gln Ser Leu Met Leu Met Ala Thr Ser Asn Glu Gly Ser Lys
65 70 75 80
Ala Thr Tyr Glu Gln Gly Val Glu Lys Asp Lys Phe Leu Ile Asn His
85 90 95
Ala Ser Leu Thr Leu Ser Thr Leu Thr Val Thr Ser Ala His Pro Glu
100 105 110
Asp Ser Ser Phe Tyr Ile Cys Ser Ala Ala Gly Gln Ala Asn Thr Glu
115 120 125
Ala Phe Phe Gly Gln Gly Thr Arg Leu Thr Val Val Glu Asp Leu Arg
130 135 140
Asn Val Thr Pro Pro Lys Val Ser Leu Phe Glu Pro Ser Lys Ala Glu
145 150 155 160
Ile Ala Asn Lys Gln Lys Ala Thr Leu Val Cys Leu Ala Arg Gly Phe
165 170 175
Phe Pro Asp His Val Glu Leu Ser Trp Trp Val Asn Gly Lys Glu Val
180 185 190
His Ser Gly Val Cys Thr Asp Pro Gln Ala Tyr Lys Glu Ser Asn Tyr
195 200 205
Ser Tyr Cys Leu Ser Ser Arg Leu Arg Val Ser Ala Thr Phe Trp His
210 215 220
Asn Pro Arg Asn His Phe Arg Cys Gln Val Gln Phe His Gly Leu Ser
225 230 235 240
Glu Glu Asp Lys Trp Pro Glu Gly Ser Pro Lys Pro Val Thr Gln Asn
245 250 255
Ile Ser Ala Glu Ala Trp Gly Arg Ala Asp Cys Gly Ile Thr Ser Ala
260 265 270
Ser Tyr Gln Gln Gly Val Leu Ser Ala Thr Ile Leu Tyr Glu Ile Leu
275 280 285
Leu Gly Lys Ala Thr Leu Tyr Ala Val Leu Val Ser Thr Leu Val Val
290 295 300
Met Ala Met Val Lys Arg Lys Asn Ser Arg Ala Lys Arg Ser Gly Ser
305 310 315 320
Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln Ala Gly Asp Val Glu Glu
325 330 335
Asn Pro Gly Pro Met His Ser Leu Arg Val Leu Leu Val Ile Leu Trp
340 345 350
Leu Gln Leu Ser Trp Val Trp Ser Gln Gln Lys Glu Val Glu Gln Asn
355 360 365
Ser Gly Pro Leu Ser Val Pro Glu Gly Ala Ile Ala Ser Leu Asn Cys
370 375 380
Thr Tyr Ser Asp Arg Gly Ser Gln Ser Phe Phe Trp Tyr Arg Gln Tyr
385 390 395 400
Ser Gly Lys Ser Pro Glu Leu Ile Met Phe Ile Tyr Ser Asn Gly Asp
405 410 415
Lys Glu Asp Gly Arg Phe Thr Ala Gln Leu Asn Lys Ala Ser Gln Tyr
420 425 430
Val Ser Leu Leu Ile Arg Asp Ser Gln Pro Ser Asp Ser Ala Thr Tyr
435 440 445
Leu Cys Ala Val Asn Asp Ala Gly Asn Met Leu Thr Phe Gly Gly Gly
450 455 460
Thr Arg Leu Met Val Lys Pro Asn Ile Gln Asn Pro Glu Pro Ala Val
465 470 475 480
Tyr Gln Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe
485 490 495
Thr Asp Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly
500 505 510
Thr Phe Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser
515 520 525
Lys Ser Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys
530 535 540
Gln Asp Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val
545 550 555 560
Pro Cys Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn
565 570 575
Leu Asn Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu
580 585 590
Lys Val Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser
595 600 605
<210> 547
<211> 602
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 547
Met Ala Ile Gly Leu Leu Cys Cys Val Ala Phe Ser Leu Leu Trp Ala
1 5 10 15
Ser Pro Val Asn Ala Gly Val Thr Gln Thr Pro Lys Phe Gln Val Leu
20 25 30
Lys Thr Gly Gln Ser Met Thr Leu Gln Cys Ala Gln Asp Met Asn His
35 40 45
Asn Ser Met Tyr Trp Tyr Arg Gln Asp Pro Gly Met Gly Leu Arg Leu
50 55 60
Ile Tyr Tyr Ser Ala Ser Glu Gly Thr Thr Asp Lys Gly Glu Val Pro
65 70 75 80
Asn Gly Tyr Asn Val Ser Arg Leu Asn Lys Arg Glu Phe Ser Leu Arg
85 90 95
Leu Glu Ser Ala Ala Pro Ser Gln Thr Ser Val Tyr Phe Cys Ala Ser
100 105 110
Ser Glu Gly Leu Trp Gln Val Gly Asp Glu Gln Tyr Phe Gly Pro Gly
115 120 125
Thr Arg Leu Thr Val Thr Glu Asp Leu Arg Asn Val Thr Pro Pro Lys
130 135 140
Val Ser Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys
145 150 155 160
Ala Thr Leu Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu
165 170 175
Leu Ser Trp Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr
180 185 190
Asp Pro Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser
195 200 205
Arg Leu Arg Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe
210 215 220
Arg Cys Gln Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro
225 230 235 240
Glu Gly Ser Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp
245 250 255
Gly Arg Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val
260 265 270
Leu Ser Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu
275 280 285
Tyr Ala Val Leu Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg
290 295 300
Lys Asn Ser Arg Ala Lys Arg Ser Gly Ser Gly Ala Thr Asn Phe Ser
305 310 315 320
Leu Leu Lys Gln Ala Gly Asp Val Glu Glu Asn Pro Gly Pro Met Ile
325 330 335
Ser Leu Arg Val Leu Leu Val Ile Leu Trp Leu Gln Leu Ser Trp Val
340 345 350
Trp Ser Gln Arg Lys Glu Val Glu Gln Asp Pro Gly Pro Phe Asn Val
355 360 365
Pro Glu Gly Ala Thr Val Ala Phe Asn Cys Thr Tyr Ser Asn Ser Ala
370 375 380
Ser Gln Ser Phe Phe Trp Tyr Arg Gln Asp Cys Arg Lys Glu Pro Lys
385 390 395 400
Leu Leu Met Ser Val Tyr Ser Ser Gly Asn Glu Asp Gly Arg Phe Thr
405 410 415
Ala Gln Leu Asn Arg Ala Ser Gln Tyr Ile Ser Leu Leu Ile Arg Asp
420 425 430
Ser Lys Leu Ser Asp Ser Ala Thr Tyr Leu Cys Val Val Gln Pro Gly
435 440 445
Gly Tyr Gln Lys Val Thr Phe Gly Thr Gly Thr Lys Leu Gln Val Ile
450 455 460
Pro Asp Ile Gln Asn Pro Glu Pro Ala Val Tyr Gln Leu Lys Asp Pro
465 470 475 480
Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr Asp Phe Asp Ser Gln
485 490 495
Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr Phe Ile Thr Asp Lys
500 505 510
Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys Ser Asn Gly Ala Ile
515 520 525
Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln Asp Ile Phe Lys Glu
530 535 540
Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro Cys Asp Ala Thr Leu
545 550 555 560
Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu Asn Phe Gln Asn Leu
565 570 575
Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys Val Ala Gly Phe Asn
580 585 590
Leu Leu Met Thr Leu Arg Leu Trp Ser Ser
595 600
<210> 548
<211> 607
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 548
Met Ala Thr Arg Leu Phe Phe Tyr Val Ala Leu Cys Leu Leu Trp Thr
1 5 10 15
Gly His Met Asp Ala Gly Ile Thr Gln Ser Pro Arg His Lys Val Thr
20 25 30
Glu Thr Gly Thr Pro Val Thr Leu Arg Cys His Gln Thr Glu Asn His
35 40 45
Arg Tyr Met Tyr Trp Tyr Arg Gln Asp Pro Gly His Gly Leu Arg Leu
50 55 60
Ile His Tyr Ser Tyr Gly Val Lys Asp Thr Asp Lys Gly Glu Val Ser
65 70 75 80
Asp Gly Tyr Ser Val Ser Arg Ser Lys Thr Glu Asp Phe Leu Leu Thr
85 90 95
Leu Glu Ser Ala Thr Ser Ser Gln Thr Ser Val Tyr Phe Cys Ala Ile
100 105 110
Ser Glu Leu Val Thr Gly Asp Ser Pro Leu His Phe Gly Asn Gly Thr
115 120 125
Arg Leu Thr Val Thr Glu Asp Leu Arg Asn Val Thr Pro Pro Lys Val
130 135 140
Ser Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys Ala
145 150 155 160
Thr Leu Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu Leu
165 170 175
Ser Trp Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr Asp
180 185 190
Pro Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser Arg
195 200 205
Leu Arg Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe Arg
210 215 220
Cys Gln Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro Glu
225 230 235 240
Gly Ser Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp Gly
245 250 255
Arg Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val Leu
260 265 270
Ser Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu Tyr
275 280 285
Ala Val Leu Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg Lys
290 295 300
Asn Ser Arg Ala Lys Arg Ser Gly Ser Gly Ala Thr Asn Phe Ser Leu
305 310 315 320
Leu Lys Gln Ala Gly Asp Val Glu Glu Asn Pro Gly Pro Met Thr Arg
325 330 335
Val Ser Leu Leu Trp Ala Val Val Val Ser Thr Cys Leu Glu Ser Gly
340 345 350
Met Ala Gln Thr Val Thr Gln Ser Gln Pro Glu Met Ser Val Gln Glu
355 360 365
Ala Glu Thr Val Thr Leu Ser Cys Thr Tyr Asp Thr Ser Glu Asn Asn
370 375 380
Tyr Tyr Leu Phe Trp Tyr Lys Gln Pro Pro Ser Arg Gln Met Ile Leu
385 390 395 400
Val Ile Arg Gln Glu Ala Tyr Lys Gln Gln Asn Ala Thr Glu Asn Arg
405 410 415
Phe Ser Val Asn Phe Gln Lys Ala Ala Lys Ser Phe Ser Leu Lys Ile
420 425 430
Ser Asp Ser Gln Leu Gly Asp Thr Ala Met Tyr Phe Cys Ala Phe Met
435 440 445
Gly Tyr Ser Gly Ala Gly Ser Tyr Gln Leu Thr Phe Gly Lys Gly Thr
450 455 460
Lys Leu Ser Val Ile Pro Asp Ile Gln Asn Pro Glu Pro Ala Val Tyr
465 470 475 480
Gln Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr
485 490 495
Asp Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr
500 505 510
Phe Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys
515 520 525
Ser Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln
530 535 540
Asp Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro
545 550 555 560
Cys Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu
565 570 575
Asn Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys
580 585 590
Val Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser
595 600 605
<210> 549
<211> 602
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 549
Met Ala Thr Arg Leu Leu Cys Trp Ala Ala Leu Cys Leu Leu Gly Ala
1 5 10 15
Glu Leu Thr Glu Ala Gly Val Ala Gln Ser Pro Arg Tyr Lys Ile Ile
20 25 30
Glu Lys Arg Gln Ser Val Ala Phe Trp Cys Asn Pro Ile Ser Gly His
35 40 45
Ala Thr Leu Tyr Trp Tyr Gln Gln Ile Leu Gly Gln Gly Pro Lys Leu
50 55 60
Leu Ile Gln Phe Gln Asn Asn Gly Val Val Asp Asp Ser Gln Leu Pro
65 70 75 80
Lys Asp Arg Phe Ser Ala Glu Arg Leu Lys Gly Val Asp Ser Thr Leu
85 90 95
Lys Ile Gln Pro Ala Lys Leu Glu Asp Ser Ala Val Tyr Leu Cys Ala
100 105 110
Ser Ser Leu Asp Pro Gly Asp Thr Gly Glu Leu Phe Phe Gly Glu Gly
115 120 125
Ser Arg Leu Thr Val Leu Glu Asp Leu Arg Asn Val Thr Pro Pro Lys
130 135 140
Val Ser Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys
145 150 155 160
Ala Thr Leu Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu
165 170 175
Leu Ser Trp Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr
180 185 190
Asp Pro Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser
195 200 205
Arg Leu Arg Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe
210 215 220
Arg Cys Gln Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro
225 230 235 240
Glu Gly Ser Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp
245 250 255
Gly Arg Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val
260 265 270
Leu Ser Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu
275 280 285
Tyr Ala Val Leu Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg
290 295 300
Lys Asn Ser Arg Ala Lys Arg Ser Gly Ser Gly Ala Thr Asn Phe Ser
305 310 315 320
Leu Leu Lys Gln Ala Gly Asp Val Glu Glu Asn Pro Gly Pro Met Glu
325 330 335
Ser Phe Leu Gly Gly Val Leu Leu Ile Leu Trp Leu Gln Val Asp Trp
340 345 350
Val Lys Ser Gln Lys Ile Glu Gln Asn Ser Glu Ala Leu Asn Ile Gln
355 360 365
Glu Gly Lys Thr Ala Thr Leu Thr Cys Asn Tyr Thr Asn Tyr Ser Pro
370 375 380
Ala Tyr Leu Gln Trp Tyr Arg Gln Asp Pro Gly Arg Gly Pro Val Phe
385 390 395 400
Leu Leu Leu Ile Arg Glu Asn Glu Lys Glu Lys Arg Lys Glu Arg Leu
405 410 415
Lys Val Thr Phe Asp Thr Thr Leu Lys Gln Ser Leu Phe His Ile Thr
420 425 430
Ala Ser Gln Pro Ala Asp Ser Ala Thr Tyr Leu Cys Ala Leu Asp Ile
435 440 445
Tyr Pro His Asp Met Arg Phe Gly Ala Gly Thr Arg Leu Thr Val Lys
450 455 460
Pro Asp Ile Gln Asn Pro Glu Pro Ala Val Tyr Gln Leu Lys Asp Pro
465 470 475 480
Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr Asp Phe Asp Ser Gln
485 490 495
Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr Phe Ile Thr Asp Lys
500 505 510
Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys Ser Asn Gly Ala Ile
515 520 525
Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln Asp Ile Phe Lys Glu
530 535 540
Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro Cys Asp Ala Thr Leu
545 550 555 560
Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu Asn Phe Gln Asn Leu
565 570 575
Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys Val Ala Gly Phe Asn
580 585 590
Leu Leu Met Thr Leu Arg Leu Trp Ser Ser
595 600
<210> 550
<211> 607
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 550
Met Ala Thr Ala Ser Leu Leu Arg Ala Val Ile Ala Ser Ile Cys Val
1 5 10 15
Val Ser Ser Met Ala Gln Lys Val Thr Gln Ala Gln Thr Glu Ile Ser
20 25 30
Val Val Glu Lys Glu Asp Val Thr Leu Asp Cys Val Tyr Glu Thr Arg
35 40 45
Asp Thr Thr Tyr Tyr Leu Phe Trp Tyr Lys Gln Pro Pro Ser Gly Glu
50 55 60
Leu Val Phe Leu Ile Arg Arg Asn Ser Phe Asp Glu Gln Asn Glu Ile
65 70 75 80
Ser Gly Arg Tyr Ser Trp Asn Phe Gln Lys Ser Thr Ser Ser Phe Asn
85 90 95
Phe Thr Ile Thr Ala Ser Gln Val Val Asp Ser Ala Val Tyr Phe Cys
100 105 110
Ala Leu Ser Glu Val Asp Ser Gly Asn Thr Pro Leu Val Phe Gly Lys
115 120 125
Gly Thr Arg Leu Ser Val Ile Ala Asn Ile Gln Asn Pro Glu Pro Ala
130 135 140
Val Tyr Gln Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu
145 150 155 160
Phe Thr Asp Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser
165 170 175
Gly Thr Phe Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp
180 185 190
Ser Lys Ser Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr
195 200 205
Cys Gln Asp Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp
210 215 220
Val Pro Cys Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met
225 230 235 240
Asn Leu Asn Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu
245 250 255
Leu Lys Val Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser
260 265 270
Ser Arg Ala Lys Arg Ser Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu
275 280 285
Lys Gln Ala Gly Asp Val Glu Glu Asn Pro Gly Pro Met His Phe Arg
290 295 300
Leu Leu Cys Cys Val Ala Phe Cys Leu Leu Gly Ala Gly Pro Val Asp
305 310 315 320
Ser Gly Val Thr Gln Thr Pro Lys His Leu Ile Thr Ala Thr Gly Gln
325 330 335
Arg Val Thr Leu Arg Cys Ser Pro Arg Ser Gly Asp Leu Ser Val Tyr
340 345 350
Trp Tyr Gln Gln Ser Leu Asp Gln Gly Leu Gln Phe Leu Ile Gln Tyr
355 360 365
Tyr Asn Gly Glu Glu Arg Ala Lys Gly Asn Ile Leu Glu Arg Phe Ser
370 375 380
Ala Gln Gln Phe Pro Asp Leu His Ser Glu Leu Asn Leu Ser Ser Leu
385 390 395 400
Glu Leu Gly Asp Ser Ala Leu Tyr Phe Cys Ala Ser Ser Val Gly Ser
405 410 415
Ser Ser Ser Thr Asp Thr Gln Tyr Phe Gly Pro Gly Thr Arg Leu Thr
420 425 430
Val Leu Glu Asp Leu Arg Asn Val Thr Pro Pro Lys Val Ser Leu Phe
435 440 445
Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys Ala Thr Leu Val
450 455 460
Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu Leu Ser Trp Trp
465 470 475 480
Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr Asp Pro Gln Ala
485 490 495
Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser Arg Leu Arg Val
500 505 510
Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe Arg Cys Gln Val
515 520 525
Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro Glu Gly Ser Pro
530 535 540
Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp Gly Arg Ala Asp
545 550 555 560
Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val Leu Ser Ala Thr
565 570 575
Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu Tyr Ala Val Leu
580 585 590
Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg Lys Asn Ser
595 600 605
<210> 551
<211> 607
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 551
Met Ala Thr Ala Ser Leu Leu Arg Ala Val Ile Ala Ser Ile Cys Val
1 5 10 15
Val Ser Ser Met Ala Gln Lys Val Thr Gln Ala Gln Thr Glu Ile Ser
20 25 30
Val Val Glu Lys Glu Asp Val Thr Leu Asp Cys Val Tyr Glu Thr Arg
35 40 45
Asp Thr Thr Tyr Tyr Leu Phe Trp Tyr Lys Gln Pro Pro Ser Gly Glu
50 55 60
Leu Val Phe Leu Ile Arg Arg Asn Ser Phe Asp Glu Gln Asn Glu Ile
65 70 75 80
Ser Gly Arg Tyr Ser Trp Asn Phe Gln Lys Ser Thr Ser Ser Phe Asn
85 90 95
Phe Thr Ile Thr Ala Ser Gln Val Val Asp Ser Ala Val Tyr Phe Cys
100 105 110
Ala Leu Ser Glu Val Asp Ser Gly Asn Thr Pro Leu Val Phe Gly Lys
115 120 125
Gly Thr Arg Leu Ser Val Ile Ala Asn Ile Gln Asn Pro Glu Pro Ala
130 135 140
Val Tyr Gln Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu
145 150 155 160
Phe Thr Asp Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser
165 170 175
Gly Thr Phe Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp
180 185 190
Ser Lys Ser Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr
195 200 205
Cys Gln Asp Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp
210 215 220
Val Pro Cys Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met
225 230 235 240
Asn Leu Asn Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu
245 250 255
Leu Lys Val Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser
260 265 270
Ser Arg Ala Lys Arg Ser Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu
275 280 285
Lys Gln Ala Gly Asp Val Glu Glu Asn Pro Gly Pro Met His Phe Arg
290 295 300
Leu Leu Cys Cys Val Ala Phe Cys Leu Leu Gly Ala Gly Pro Val Asp
305 310 315 320
Ser Gly Val Thr Gln Thr Pro Lys His Leu Ile Thr Ala Thr Gly Gln
325 330 335
Arg Val Thr Leu Arg Cys Ser Pro Arg Ser Gly Asp Leu Ser Val Tyr
340 345 350
Trp Tyr Gln Gln Ser Leu Asp Gln Gly Leu Gln Phe Leu Ile His Tyr
355 360 365
Tyr Asn Gly Glu Glu Arg Ala Lys Gly Asn Ile Leu Glu Arg Phe Ser
370 375 380
Ala Gln Gln Phe Pro Asp Leu His Ser Glu Leu Asn Leu Ser Ser Leu
385 390 395 400
Glu Leu Gly Asp Ser Ala Leu Tyr Phe Cys Ala Ser Ser Val Gly Ser
405 410 415
Ser Ser Ser Thr Asp Thr Gln Tyr Phe Gly Pro Gly Thr Arg Leu Thr
420 425 430
Val Leu Glu Asp Leu Arg Asn Val Thr Pro Pro Lys Val Ser Leu Phe
435 440 445
Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys Ala Thr Leu Val
450 455 460
Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu Leu Ser Trp Trp
465 470 475 480
Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr Asp Pro Gln Ala
485 490 495
Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser Arg Leu Arg Val
500 505 510
Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe Arg Cys Gln Val
515 520 525
Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro Glu Gly Ser Pro
530 535 540
Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp Gly Arg Ala Asp
545 550 555 560
Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val Leu Ser Ala Thr
565 570 575
Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu Tyr Ala Val Leu
580 585 590
Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg Lys Asn Ser
595 600 605
<210> 552
<211> 611
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 552
Met Ala Lys Ser Leu Arg Val Leu Leu Val Ile Leu Trp Leu Gln Leu
1 5 10 15
Ser Trp Val Trp Ser Gln Gln Lys Glu Val Glu Gln Asp Pro Gly Pro
20 25 30
Leu Ser Val Pro Glu Gly Ala Ile Val Ser Leu Asn Cys Thr Tyr Ser
35 40 45
Asn Ser Ala Phe Gln Tyr Phe Met Trp Tyr Arg Gln Tyr Ser Arg Lys
50 55 60
Gly Pro Glu Leu Leu Met Tyr Thr Tyr Ser Ser Gly Asn Lys Glu Asp
65 70 75 80
Gly Arg Phe Thr Ala Gln Val Asp Lys Ser Ser Lys Tyr Ile Ser Leu
85 90 95
Phe Ile Arg Asp Ser Gln Pro Ser Asp Ser Ala Thr Tyr Leu Cys Ala
100 105 110
Met Thr Ser Pro Tyr Asn Asn Asn Asp Met Arg Phe Gly Ala Gly Thr
115 120 125
Arg Leu Thr Val Lys Pro Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr
130 135 140
Gln Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr
145 150 155 160
Asp Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr
165 170 175
Phe Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys
180 185 190
Ser Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln
195 200 205
Asp Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro
210 215 220
Cys Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu
225 230 235 240
Asn Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys
245 250 255
Val Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser Arg
260 265 270
Ala Lys Arg Ser Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln
275 280 285
Ala Gly Asp Val Glu Glu Asn Pro Gly Pro Met His Leu Leu Leu Leu
290 295 300
Leu Leu Gly Pro Gly Ile Ser Leu Leu Leu Pro Gly Ser Leu Ala Gly
305 310 315 320
Ser Gly Leu Gly Ala Val Val Ser Gln His Pro Ser Trp Val Ile Cys
325 330 335
Lys Ser Gly Thr Ser Val Lys Ile Glu Cys Arg Ser Leu Asp Phe Gln
340 345 350
Ala Thr Thr Met Phe Trp Tyr Arg Gln Phe Pro Lys Gln Ser Leu Met
355 360 365
Leu Met Ala Thr Ser Asn Glu Gly Ser Lys Ala Thr Tyr Glu Gln Gly
370 375 380
Val Glu Lys Asp Lys Phe Leu Ile Asn His Ala Ser Leu Thr Leu Ser
385 390 395 400
Thr Leu Thr Val Thr Ser Ala His Pro Glu Asp Ser Ser Phe Tyr Ile
405 410 415
Cys Ser Gly Gly Leu Glu Glu Ala Ala Arg Gln Phe Ile Gly Pro Gly
420 425 430
Thr Arg Leu Thr Val Leu Glu Asp Leu Arg Asn Val Thr Pro Pro Lys
435 440 445
Val Ser Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys
450 455 460
Ala Thr Leu Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu
465 470 475 480
Leu Ser Trp Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr
485 490 495
Asp Pro Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser
500 505 510
Arg Leu Arg Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe
515 520 525
Arg Cys Gln Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro
530 535 540
Glu Gly Ser Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp
545 550 555 560
Gly Arg Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val
565 570 575
Leu Ser Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu
580 585 590
Tyr Ala Val Leu Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg
595 600 605
Lys Asn Ser
610
<210> 553
<211> 601
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 553
Met Ala Lys Ser Leu Arg Val Leu Leu Val Ile Leu Trp Leu Gln Leu
1 5 10 15
Ser Trp Val Trp Ser Gln Gln Lys Glu Val Glu Gln Asp Pro Gly Pro
20 25 30
Leu Ser Val Pro Glu Gly Ala Ile Val Ser Leu Asn Cys Thr Tyr Ser
35 40 45
Asn Ser Ala Phe Gln Tyr Phe Met Trp Tyr Arg Gln Tyr Ser Arg Lys
50 55 60
Gly Pro Glu Leu Leu Met Tyr Thr Tyr Ser Ser Gly Asn Lys Glu Asp
65 70 75 80
Gly Arg Phe Thr Ala Gln Val Asp Lys Ser Ser Lys Tyr Ile Ser Leu
85 90 95
Phe Ile Arg Asp Ser Gln Pro Ser Asp Ser Ala Thr Tyr Leu Cys Ala
100 105 110
Met Thr Ser Pro Tyr Asn Asn Asn Asp Met Arg Phe Gly Ala Gly Thr
115 120 125
Arg Leu Thr Val Lys Pro Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr
130 135 140
Gln Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr
145 150 155 160
Asp Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr
165 170 175
Phe Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys
180 185 190
Ser Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln
195 200 205
Asp Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro
210 215 220
Cys Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu
225 230 235 240
Asn Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys
245 250 255
Val Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser Arg
260 265 270
Ala Lys Arg Ser Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln
275 280 285
Ala Gly Asp Val Glu Glu Asn Pro Gly Pro Met His Leu Leu Leu Leu
290 295 300
Leu Leu Gly Pro Ala Gly Ser Gly Leu Gly Ala Val Val Ser Gln His
305 310 315 320
Pro Ser Arg Val Ile Cys Lys Ser Gly Thr Ser Val Lys Ile Glu Cys
325 330 335
Arg Ser Leu Asp Phe Gln Ala Thr Thr Met Phe Trp Tyr Arg Gln Phe
340 345 350
Pro Lys Gln Ser Leu Met Leu Met Ala Thr Ser Asn Glu Gly Ser Lys
355 360 365
Ala Thr Tyr Glu Gln Gly Val Glu Lys Asp Lys Phe Leu Ile Asn His
370 375 380
Ala Ser Leu Thr Leu Ser Thr Leu Thr Val Thr Ser Ala His Pro Glu
385 390 395 400
Asp Ser Ser Phe Tyr Ile Cys Ser Gly Gly Leu Glu Glu Ala Ala Arg
405 410 415
Gln Phe Ile Gly Pro Gly Thr Arg Leu Thr Val Leu Glu Asp Leu Arg
420 425 430
Asn Val Thr Pro Pro Lys Val Ser Leu Phe Glu Pro Ser Lys Ala Glu
435 440 445
Ile Ala Asn Lys Gln Lys Ala Thr Leu Val Cys Leu Ala Arg Gly Phe
450 455 460
Phe Pro Asp His Val Glu Leu Ser Trp Trp Val Asn Gly Lys Glu Val
465 470 475 480
His Ser Gly Val Cys Thr Asp Pro Gln Ala Tyr Lys Glu Ser Asn Tyr
485 490 495
Ser Tyr Cys Leu Ser Ser Arg Leu Arg Val Ser Ala Thr Phe Trp His
500 505 510
Asn Pro Arg Asn His Phe Arg Cys Gln Val Gln Phe His Gly Leu Ser
515 520 525
Glu Glu Asp Lys Trp Pro Glu Gly Ser Pro Lys Pro Val Thr Gln Asn
530 535 540
Ile Ser Ala Glu Ala Trp Gly Arg Ala Asp Cys Gly Ile Thr Ser Ala
545 550 555 560
Ser Tyr Gln Gln Gly Val Leu Ser Ala Thr Ile Leu Tyr Glu Ile Leu
565 570 575
Leu Gly Lys Ala Thr Leu Tyr Ala Val Leu Val Ser Thr Leu Val Val
580 585 590
Met Ala Met Val Lys Arg Lys Asn Ser
595 600
<210> 554
<211> 596
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 554
Met Ala Leu Val Ala Arg Val Thr Val Phe Leu Thr Phe Gly Thr Ile
1 5 10 15
Ile Asp Ala Lys Thr Thr Gln Pro Pro Ser Met Asp Cys Ala Glu Gly
20 25 30
Arg Ala Ala Asn Leu Pro Cys Asn His Ser Thr Ile Ser Gly Asn Glu
35 40 45
Tyr Val Tyr Trp Tyr Arg Gln Ile His Ser Gln Gly Pro Gln Tyr Ile
50 55 60
Ile His Gly Leu Lys Asn Asn Glu Thr Asn Glu Met Ala Ser Leu Ile
65 70 75 80
Ile Thr Glu Asp Arg Lys Ser Ser Thr Leu Ile Leu Pro His Ala Thr
85 90 95
Leu Arg Asp Thr Ala Val Tyr Tyr Cys Ile Val Pro Asn Asp Tyr Lys
100 105 110
Leu Ser Phe Gly Ala Gly Thr Thr Val Thr Val Arg Ala Asn Ile Gln
115 120 125
Asn Pro Glu Pro Ala Val Tyr Gln Leu Lys Asp Pro Arg Ser Gln Asp
130 135 140
Ser Thr Leu Cys Leu Phe Thr Asp Phe Asp Ser Gln Ile Asn Val Pro
145 150 155 160
Lys Thr Met Glu Ser Gly Thr Phe Ile Thr Asp Lys Cys Val Leu Asp
165 170 175
Met Lys Ala Met Asp Ser Lys Ser Asn Gly Ala Ile Ala Trp Ser Asn
180 185 190
Gln Thr Ser Phe Thr Cys Gln Asp Ile Phe Lys Glu Thr Asn Ala Thr
195 200 205
Tyr Pro Ser Ser Asp Val Pro Cys Asp Ala Thr Leu Thr Glu Lys Ser
210 215 220
Phe Glu Thr Asp Met Asn Leu Asn Phe Gln Asn Leu Leu Val Ile Val
225 230 235 240
Leu Arg Ile Leu Leu Leu Lys Val Ala Gly Phe Asn Leu Leu Met Thr
245 250 255
Leu Arg Leu Trp Ser Ser Arg Ala Lys Arg Ser Gly Ser Gly Ala Thr
260 265 270
Asn Phe Ser Leu Leu Lys Gln Ala Gly Asp Val Glu Glu Asn Pro Gly
275 280 285
Pro Met His Ile Arg Leu Leu Cys Arg Val Ala Phe Cys Phe Leu Ala
290 295 300
Val Gly Leu Val Asp Val Lys Val Thr Gln Ser Ser Arg Tyr Leu Val
305 310 315 320
Lys Arg Thr Gly Glu Lys Val Phe Leu Glu Cys Val Gln Asp Met Asp
325 330 335
His Glu Asn Met Phe Trp Tyr Arg Gln Asp Pro Gly Leu Gly Leu Arg
340 345 350
Leu Ile Tyr Phe Ser Tyr Asp Val Lys Met Lys Glu Lys Gly Asp Ile
355 360 365
Pro Glu Gly Tyr Ser Val Ser Arg Glu Lys Lys Glu Arg Phe Ser Leu
370 375 380
Ile Leu Glu Ser Ala Ser Thr Asn Gln Thr Ser Met Tyr Leu Cys Ala
385 390 395 400
Ser Ser Phe Gly Thr Gly Ser Ile Gln Glu Thr Gln Tyr Phe Gly Pro
405 410 415
Gly Thr Arg Leu Leu Val Leu Glu Asp Leu Arg Asn Val Thr Pro Pro
420 425 430
Lys Val Ser Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln
435 440 445
Lys Ala Thr Leu Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val
450 455 460
Glu Leu Ser Trp Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys
465 470 475 480
Thr Asp Pro Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser
485 490 495
Ser Arg Leu Arg Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn His
500 505 510
Phe Arg Cys Gln Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp
515 520 525
Pro Glu Gly Ser Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala
530 535 540
Trp Gly Arg Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly
545 550 555 560
Val Leu Ser Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr
565 570 575
Leu Tyr Ala Val Leu Val Ser Thr Leu Val Val Met Ala Met Val Lys
580 585 590
Arg Lys Asn Ser
595
<210> 555
<211> 610
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 555
Met Ala Tyr Ser Pro Gly Leu Val Ser Leu Ile Leu Leu Leu Leu Gly
1 5 10 15
Arg Thr Arg Gly Asn Ser Val Thr Gln Met Glu Gly Pro Val Thr Leu
20 25 30
Ser Glu Glu Ala Phe Leu Thr Ile Asn Cys Thr Tyr Thr Ala Thr Gly
35 40 45
Tyr Pro Ser Leu Phe Trp Tyr Val Gln Tyr Pro Gly Glu Gly Leu Gln
50 55 60
Leu Leu Leu Lys Ala Thr Lys Ala Asp Asp Lys Gly Ser Asn Lys Gly
65 70 75 80
Phe Glu Ala Thr Tyr Arg Lys Glu Thr Thr Ser Phe His Leu Glu Lys
85 90 95
Gly Ser Val Gln Val Ser Asp Ser Ala Val Tyr Phe Cys Ala Leu Asn
100 105 110
Pro Asn Ala Gly Gly Thr Ser Tyr Gly Lys Leu Thr Phe Gly Gln Gly
115 120 125
Thr Ile Leu Thr Val His Pro Asn Ile Gln Asn Pro Glu Pro Ala Val
130 135 140
Tyr Gln Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe
145 150 155 160
Thr Asp Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly
165 170 175
Thr Phe Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser
180 185 190
Lys Ser Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys
195 200 205
Gln Asp Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val
210 215 220
Pro Cys Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn
225 230 235 240
Leu Asn Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu
245 250 255
Lys Val Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser
260 265 270
Arg Ala Lys Arg Ser Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys
275 280 285
Gln Ala Gly Asp Val Glu Glu Asn Pro Gly Pro Met His Pro Arg Leu
290 295 300
Leu Phe Trp Ala Leu Leu Cys Leu Leu Gly Thr Gly Pro Val Glu Ala
305 310 315 320
Gly Val Thr Gln Ser Pro Thr His Leu Ile Lys Thr Arg Gly Gln Gln
325 330 335
Ala Thr Leu Arg Cys Ser Pro Ile Ser Gly His Thr Ser Val Tyr Trp
340 345 350
Tyr Gln Gln Ala Leu Gly Leu Gly Leu Gln Phe Leu Leu Trp Tyr Asp
355 360 365
Glu Gly Glu Glu Arg Asn Arg Gly Asn Phe Pro Pro Arg Phe Ser Gly
370 375 380
Arg Gln Phe Pro Asn Tyr Ser Ser Glu Leu Asn Val Asn Ala Leu Glu
385 390 395 400
Leu Glu Asp Ser Ala Leu Tyr Leu Cys Ala Ser Ser Ser Pro Gly Ala
405 410 415
Thr Ser Gly Gly Ala Asn Thr Gly Glu Leu Phe Phe Gly Glu Gly Ser
420 425 430
Arg Leu Thr Val Leu Glu Asp Leu Arg Asn Val Thr Pro Pro Lys Val
435 440 445
Ser Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys Ala
450 455 460
Thr Leu Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu Leu
465 470 475 480
Ser Trp Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr Asp
485 490 495
Pro Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser Arg
500 505 510
Leu Arg Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe Arg
515 520 525
Cys Gln Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro Glu
530 535 540
Gly Ser Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp Gly
545 550 555 560
Arg Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val Leu
565 570 575
Ser Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu Tyr
580 585 590
Ala Val Leu Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg Lys
595 600 605
Asn Ser
610
<210> 556
<211> 614
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 556
Met Ala Thr Phe Ala Gly Phe Ser Phe Leu Phe Leu Trp Leu Gln Leu
1 5 10 15
Asp Cys Met Ser Arg Gly Glu Asp Val Glu Gln Ser Leu Phe Leu Ser
20 25 30
Val Arg Glu Gly Asp Ser Ser Val Ile Asn Cys Thr Tyr Thr Asp Ser
35 40 45
Ser Ser Thr Tyr Leu Tyr Trp Tyr Lys Gln Glu Pro Gly Ala Gly Leu
50 55 60
Gln Leu Leu Thr Tyr Ile Phe Ser Asn Met Asp Met Lys Gln Asp Gln
65 70 75 80
Arg Leu Thr Val Leu Leu Asn Lys Lys Asp Lys His Leu Ser Leu Arg
85 90 95
Ile Ala Asp Thr Gln Thr Gly Asp Ser Ala Ile Tyr Phe Cys Ala Glu
100 105 110
Ile Pro Arg Asp Ser Gly Gly Gly Ala Asp Gly Leu Thr Phe Gly Lys
115 120 125
Gly Thr His Leu Ile Ile Gln Pro Asn Ile Gln Asn Pro Glu Pro Ala
130 135 140
Val Tyr Gln Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu
145 150 155 160
Phe Thr Asp Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser
165 170 175
Gly Thr Phe Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp
180 185 190
Ser Lys Ser Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr
195 200 205
Cys Gln Asp Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp
210 215 220
Val Pro Cys Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met
225 230 235 240
Asn Leu Asn Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu
245 250 255
Leu Lys Val Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser
260 265 270
Ser Arg Ala Lys Arg Ser Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu
275 280 285
Lys Gln Ala Gly Asp Val Glu Glu Asn Pro Gly Pro Met His Leu Leu
290 295 300
Leu Leu Leu Leu Gly Pro Gly Ile Ser Leu Leu Leu Pro Gly Ser Leu
305 310 315 320
Ala Gly Ser Gly Leu Gly Ala Val Val Ser Gln His Pro Ser Trp Val
325 330 335
Ile Cys Lys Ser Gly Thr Ser Val Lys Ile Glu Cys Arg Ser Leu Asp
340 345 350
Phe Gln Ala Thr Thr Met Phe Trp Tyr Arg Gln Phe Pro Lys Gln Ser
355 360 365
Leu Met Leu Met Ala Thr Ser Asn Glu Gly Ser Lys Ala Thr Tyr Glu
370 375 380
Gln Gly Val Glu Lys Asp Lys Phe Leu Ile Asn His Ala Ser Leu Thr
385 390 395 400
Leu Ser Thr Leu Thr Val Thr Ser Ala His Pro Glu Asp Ser Ser Phe
405 410 415
Tyr Ile Cys Ser Ala Arg Asp Leu Gln Arg Ser Tyr Glu Gln Tyr Phe
420 425 430
Gly Pro Gly Thr Arg Leu Thr Val Thr Glu Asp Leu Arg Asn Val Thr
435 440 445
Pro Pro Lys Val Ser Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn
450 455 460
Lys Gln Lys Ala Thr Leu Val Cys Leu Ala Arg Gly Phe Phe Pro Asp
465 470 475 480
His Val Glu Leu Ser Trp Trp Val Asn Gly Lys Glu Val His Ser Gly
485 490 495
Val Cys Thr Asp Pro Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys
500 505 510
Leu Ser Ser Arg Leu Arg Val Ser Ala Thr Phe Trp His Asn Pro Arg
515 520 525
Asn His Phe Arg Cys Gln Val Gln Phe His Gly Leu Ser Glu Glu Asp
530 535 540
Lys Trp Pro Glu Gly Ser Pro Lys Pro Val Thr Gln Asn Ile Ser Ala
545 550 555 560
Glu Ala Trp Gly Arg Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln
565 570 575
Gln Gly Val Leu Ser Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys
580 585 590
Ala Thr Leu Tyr Ala Val Leu Val Ser Thr Leu Val Val Met Ala Met
595 600 605
Val Lys Arg Lys Asn Ser
610
<210> 557
<211> 604
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 557
Met Ala Thr Phe Ala Gly Phe Ser Phe Leu Phe Leu Trp Leu Gln Leu
1 5 10 15
Asp Cys Met Ser Arg Gly Glu Asp Val Glu Gln Ser Leu Phe Leu Ser
20 25 30
Val Arg Glu Gly Asp Ser Ser Val Ile Asn Cys Thr Tyr Thr Asp Ser
35 40 45
Ser Ser Thr Tyr Leu Tyr Trp Tyr Lys Gln Glu Pro Gly Ala Gly Leu
50 55 60
Gln Leu Leu Thr Tyr Ile Phe Ser Asn Met Asp Met Lys Gln Asp Gln
65 70 75 80
Arg Leu Thr Val Leu Leu Asn Lys Lys Asp Lys His Leu Ser Leu Arg
85 90 95
Ile Ala Asp Thr Gln Thr Gly Asp Ser Ala Ile Tyr Phe Cys Ala Glu
100 105 110
Ile Pro Arg Asp Ser Gly Gly Gly Ala Asp Gly Leu Thr Phe Gly Lys
115 120 125
Gly Thr His Leu Ile Ile Gln Pro Asn Ile Gln Asn Pro Glu Pro Ala
130 135 140
Val Tyr Gln Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu
145 150 155 160
Phe Thr Asp Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser
165 170 175
Gly Thr Phe Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp
180 185 190
Ser Lys Ser Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr
195 200 205
Cys Gln Asp Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp
210 215 220
Val Pro Cys Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met
225 230 235 240
Asn Leu Asn Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu
245 250 255
Leu Lys Val Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser
260 265 270
Ser Arg Ala Lys Arg Ser Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu
275 280 285
Lys Gln Ala Gly Asp Val Glu Glu Asn Pro Gly Pro Met His Leu Leu
290 295 300
Leu Leu Leu Leu Gly Pro Ala Gly Ser Gly Leu Gly Ala Val Val Ser
305 310 315 320
Gln His Pro Ser Arg Val Ile Cys Lys Ser Gly Thr Ser Val Lys Ile
325 330 335
Glu Cys Arg Ser Leu Asp Phe Gln Ala Thr Thr Met Phe Trp Tyr Arg
340 345 350
Gln Phe Pro Lys Gln Ser Leu Met Leu Met Ala Thr Ser Asn Glu Gly
355 360 365
Ser Lys Ala Thr Tyr Glu Gln Gly Val Glu Lys Asp Lys Phe Leu Ile
370 375 380
Asn His Ala Ser Leu Thr Leu Ser Thr Leu Thr Val Thr Ser Ala His
385 390 395 400
Pro Glu Asp Ser Ser Phe Tyr Ile Cys Ser Ala Arg Asp Leu Gln Arg
405 410 415
Ser Tyr Glu Gln Tyr Phe Gly Pro Gly Thr Arg Leu Thr Val Thr Glu
420 425 430
Asp Leu Arg Asn Val Thr Pro Pro Lys Val Ser Leu Phe Glu Pro Ser
435 440 445
Lys Ala Glu Ile Ala Asn Lys Gln Lys Ala Thr Leu Val Cys Leu Ala
450 455 460
Arg Gly Phe Phe Pro Asp His Val Glu Leu Ser Trp Trp Val Asn Gly
465 470 475 480
Lys Glu Val His Ser Gly Val Cys Thr Asp Pro Gln Ala Tyr Lys Glu
485 490 495
Ser Asn Tyr Ser Tyr Cys Leu Ser Ser Arg Leu Arg Val Ser Ala Thr
500 505 510
Phe Trp His Asn Pro Arg Asn His Phe Arg Cys Gln Val Gln Phe His
515 520 525
Gly Leu Ser Glu Glu Asp Lys Trp Pro Glu Gly Ser Pro Lys Pro Val
530 535 540
Thr Gln Asn Ile Ser Ala Glu Ala Trp Gly Arg Ala Asp Cys Gly Ile
545 550 555 560
Thr Ser Ala Ser Tyr Gln Gln Gly Val Leu Ser Ala Thr Ile Leu Tyr
565 570 575
Glu Ile Leu Leu Gly Lys Ala Thr Leu Tyr Ala Val Leu Val Ser Thr
580 585 590
Leu Val Val Met Ala Met Val Lys Arg Lys Asn Ser
595 600
<210> 558
<211> 606
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 558
Met Ala Gly Ile Arg Ala Leu Phe Met Tyr Leu Trp Leu Gln Leu Asp
1 5 10 15
Trp Val Ser Arg Gly Glu Ser Val Gly Leu His Leu Pro Thr Leu Ser
20 25 30
Val Gln Glu Gly Asp Asn Ser Ile Ile Asn Cys Ala Tyr Ser Asn Ser
35 40 45
Ala Ser Asp Tyr Phe Ile Trp Tyr Lys Gln Glu Ser Gly Lys Gly Pro
50 55 60
Gln Phe Ile Ile Asp Ile Arg Ser Asn Met Asp Lys Arg Gln Gly Gln
65 70 75 80
Arg Val Thr Val Leu Leu Asn Lys Thr Val Lys His Leu Ser Leu Gln
85 90 95
Ile Ala Ala Thr Gln Pro Gly Asp Ser Ala Val Tyr Phe Cys Ala Glu
100 105 110
Pro Val Gly Gly Leu Asn Ser Gly Tyr Ala Leu Asn Phe Gly Lys Gly
115 120 125
Thr Ser Leu Leu Val Thr Pro Asn Ile Gln Asn Pro Glu Pro Ala Val
130 135 140
Tyr Gln Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe
145 150 155 160
Thr Asp Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly
165 170 175
Thr Phe Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser
180 185 190
Lys Ser Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys
195 200 205
Gln Asp Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val
210 215 220
Pro Cys Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn
225 230 235 240
Leu Asn Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu
245 250 255
Lys Val Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser
260 265 270
Arg Ala Lys Arg Ser Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys
275 280 285
Gln Ala Gly Asp Val Glu Glu Asn Pro Gly Pro Met His Pro Gly Leu
290 295 300
Leu Cys Trp Val Leu Leu Cys Leu Leu Gly Ala Gly Pro Val Asp Ala
305 310 315 320
Gly Val Thr Gln Ser Pro Thr His Leu Ile Lys Thr Arg Gly Gln Gln
325 330 335
Val Thr Leu Arg Cys Ser Pro Ile Ser Gly His Lys Ser Val Ser Trp
340 345 350
Tyr Gln Gln Val Leu Gly Gln Gly Pro Gln Phe Ile Phe Gln Tyr Tyr
355 360 365
Glu Lys Glu Glu Arg Gly Arg Gly Asn Phe Pro Asp Arg Phe Ser Ala
370 375 380
Arg Gln Phe Pro Asn Tyr Ser Ser Glu Leu Asn Val Asn Ala Leu Leu
385 390 395 400
Leu Gly Asp Ser Ala Leu Tyr Leu Cys Ala Ser Ser Gly Gly Arg Thr
405 410 415
Ser Gly Ala Tyr Glu Gln Phe Phe Gly Pro Gly Thr Arg Leu Thr Val
420 425 430
Leu Glu Asp Leu Arg Asn Val Thr Pro Pro Lys Val Ser Leu Phe Glu
435 440 445
Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys Ala Thr Leu Val Cys
450 455 460
Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu Leu Ser Trp Trp Val
465 470 475 480
Asn Gly Lys Glu Val His Ser Gly Val Cys Thr Asp Pro Gln Ala Tyr
485 490 495
Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser Arg Leu Arg Val Ser
500 505 510
Ala Thr Phe Trp His Asn Pro Arg Asn His Phe Arg Cys Gln Val Gln
515 520 525
Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro Glu Gly Ser Pro Lys
530 535 540
Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp Gly Arg Ala Asp Cys
545 550 555 560
Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val Leu Ser Ala Thr Ile
565 570 575
Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu Tyr Ala Val Leu Val
580 585 590
Ser Thr Leu Val Val Met Ala Met Val Lys Arg Lys Asn Ser
595 600 605
<210> 559
<211> 604
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 559
Met Ala Lys Met Leu Glu Cys Ala Phe Ile Val Leu Trp Leu Gln Leu
1 5 10 15
Gly Trp Leu Ser Gly Glu Asp Gln Val Thr Gln Ser Pro Glu Ala Leu
20 25 30
Arg Leu Gln Glu Gly Glu Ser Ser Ser Leu Asn Cys Ser Tyr Thr Val
35 40 45
Ser Gly Leu Arg Gly Leu Phe Trp Tyr Arg Gln Asp Pro Gly Lys Gly
50 55 60
Pro Glu Phe Leu Phe Thr Leu Tyr Ser Ala Gly Glu Glu Lys Glu Lys
65 70 75 80
Glu Arg Leu Lys Ala Thr Leu Thr Lys Lys Glu Ser Phe Leu His Ile
85 90 95
Thr Ala Pro Lys Pro Glu Asp Ser Ala Thr Tyr Leu Cys Ala Val Thr
100 105 110
Ala His Arg Gly Ser Thr Leu Gly Arg Leu Tyr Phe Gly Arg Gly Thr
115 120 125
Gln Leu Thr Val Trp Pro Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr
130 135 140
Gln Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr
145 150 155 160
Asp Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr
165 170 175
Phe Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys
180 185 190
Ser Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln
195 200 205
Asp Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro
210 215 220
Cys Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu
225 230 235 240
Asn Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys
245 250 255
Val Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser Arg
260 265 270
Ala Lys Arg Ser Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln
275 280 285
Ala Gly Asp Val Glu Glu Asn Pro Gly Pro Met His Pro Gly Leu Leu
290 295 300
Cys Trp Ala Leu Leu Cys Leu Leu Gly Ala Gly Leu Val Asp Ala Gly
305 310 315 320
Val Thr Gln Ser Pro Thr His Leu Ile Lys Thr Arg Gly Gln Gln Val
325 330 335
Thr Leu Arg Cys Ser Pro Lys Ser Gly His Asp Thr Val Ser Trp Tyr
340 345 350
Gln Gln Ala Leu Gly Gln Gly Pro Gln Phe Ile Phe Gln Tyr Tyr Glu
355 360 365
Glu Glu Glu Arg Gln Arg Gly Asn Phe Pro Asp Arg Phe Ser Gly His
370 375 380
Gln Phe Pro Asn Tyr Ser Ser Glu Leu Asn Val Asn Ala Leu Leu Leu
385 390 395 400
Gly Asp Ser Ala Leu Tyr Leu Cys Ala Ser Ser Arg Arg Gly Gly Ala
405 410 415
Tyr Asn Glu Gln Phe Phe Gly Pro Gly Thr Arg Leu Thr Val Leu Glu
420 425 430
Asp Leu Arg Asn Val Thr Pro Pro Lys Val Ser Leu Phe Glu Pro Ser
435 440 445
Lys Ala Glu Ile Ala Asn Lys Gln Lys Ala Thr Leu Val Cys Leu Ala
450 455 460
Arg Gly Phe Phe Pro Asp His Val Glu Leu Ser Trp Trp Val Asn Gly
465 470 475 480
Lys Glu Val His Ser Gly Val Cys Thr Asp Pro Gln Ala Tyr Lys Glu
485 490 495
Ser Asn Tyr Ser Tyr Cys Leu Ser Ser Arg Leu Arg Val Ser Ala Thr
500 505 510
Phe Trp His Asn Pro Arg Asn His Phe Arg Cys Gln Val Gln Phe His
515 520 525
Gly Leu Ser Glu Glu Asp Lys Trp Pro Glu Gly Ser Pro Lys Pro Val
530 535 540
Thr Gln Asn Ile Ser Ala Glu Ala Trp Gly Arg Ala Asp Cys Gly Ile
545 550 555 560
Thr Ser Ala Ser Tyr Gln Gln Gly Val Leu Ser Ala Thr Ile Leu Tyr
565 570 575
Glu Ile Leu Leu Gly Lys Ala Thr Leu Tyr Ala Val Leu Val Ser Thr
580 585 590
Leu Val Val Met Ala Met Val Lys Arg Lys Asn Ser
595 600
<210> 560
<211> 605
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 560
Met Ala Lys Asn Pro Leu Ala Ala Pro Leu Leu Ile Leu Trp Phe His
1 5 10 15
Leu Asp Cys Val Ser Ser Ile Leu Asn Val Glu Gln Ser Pro Gln Ser
20 25 30
Leu His Val Gln Glu Gly Asp Ser Thr Asn Phe Thr Cys Ser Phe Pro
35 40 45
Ser Ser Asn Phe Tyr Ala Leu His Trp Tyr Arg Trp Glu Thr Ala Lys
50 55 60
Ser Pro Glu Ala Leu Phe Val Met Thr Leu Asn Gly Asp Glu Lys Lys
65 70 75 80
Lys Gly Arg Ile Ser Ala Thr Leu Asn Thr Lys Glu Gly Tyr Ser Tyr
85 90 95
Leu Tyr Ile Lys Gly Ser Gln Pro Glu Asp Ser Ala Thr Tyr Leu Cys
100 105 110
Ala Ser Val Gly Gly Gly Ala Asp Gly Leu Thr Phe Gly Lys Gly Thr
115 120 125
His Leu Ile Ile Gln Pro Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr
130 135 140
Gln Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr
145 150 155 160
Asp Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr
165 170 175
Phe Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys
180 185 190
Ser Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln
195 200 205
Asp Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro
210 215 220
Cys Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu
225 230 235 240
Asn Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys
245 250 255
Val Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser Arg
260 265 270
Ala Lys Arg Ser Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln
275 280 285
Ala Gly Asp Val Glu Glu Asn Pro Gly Pro Met His Thr Arg Leu Leu
290 295 300
Phe Trp Val Ala Phe Cys Leu Leu Gly Ala Asp His Thr Gly Ala Gly
305 310 315 320
Val Ser Gln Ser Pro Ser Asn Lys Val Thr Glu Lys Gly Lys Asp Val
325 330 335
Glu Leu Arg Cys Asp Pro Ile Ser Gly His Thr Ala Leu Tyr Trp Tyr
340 345 350
Arg Gln Ser Leu Gly Gln Gly Leu Glu Phe Leu Ile Tyr Phe Gln Gly
355 360 365
Asn Ser Ala Pro Asp Lys Ser Gly Leu Pro Ser Asp Arg Phe Ser Ala
370 375 380
Glu Arg Thr Gly Gly Ser Val Ser Thr Leu Thr Ile Gln Arg Thr Gln
385 390 395 400
Gln Glu Asp Ser Ala Val Tyr Leu Cys Ala Ser Thr Trp Asp Arg Gly
405 410 415
Ser Tyr Asn Glu Gln Phe Phe Gly Pro Gly Thr Arg Leu Thr Val Leu
420 425 430
Glu Asp Leu Arg Asn Val Thr Pro Pro Lys Val Ser Leu Phe Glu Pro
435 440 445
Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys Ala Thr Leu Val Cys Leu
450 455 460
Ala Arg Gly Phe Phe Pro Asp His Val Glu Leu Ser Trp Trp Val Asn
465 470 475 480
Gly Lys Glu Val His Ser Gly Val Cys Thr Asp Pro Gln Ala Tyr Lys
485 490 495
Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser Arg Leu Arg Val Ser Ala
500 505 510
Thr Phe Trp His Asn Pro Arg Asn His Phe Arg Cys Gln Val Gln Phe
515 520 525
His Gly Leu Ser Glu Glu Asp Lys Trp Pro Glu Gly Ser Pro Lys Pro
530 535 540
Val Thr Gln Asn Ile Ser Ala Glu Ala Trp Gly Arg Ala Asp Cys Gly
545 550 555 560
Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val Leu Ser Ala Thr Ile Leu
565 570 575
Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu Tyr Ala Val Leu Val Ser
580 585 590
Thr Leu Val Val Met Ala Met Val Lys Arg Lys Asn Ser
595 600 605
<210> 561
<211> 602
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 561
Met Ala Lys Cys Pro Gln Ala Leu Leu Ala Ile Phe Trp Leu Leu Leu
1 5 10 15
Ser Trp Val Ser Ser Glu Asp Lys Val Val Gln Ser Pro Leu Ser Leu
20 25 30
Val Val His Glu Gly Asp Thr Val Thr Leu Asn Cys Ser Tyr Glu Val
35 40 45
Thr Asn Phe Arg Ser Leu Leu Trp Tyr Lys Gln Glu Lys Lys Ala Pro
50 55 60
Thr Phe Leu Phe Met Leu Thr Ser Ser Gly Ile Glu Lys Lys Ser Gly
65 70 75 80
Arg Leu Ser Ser Ile Leu Asp Lys Lys Glu Leu Ser Ser Ile Leu Asn
85 90 95
Ile Thr Ala Thr Gln Thr Gly Asp Ser Ala Ile Tyr Leu Cys Ala Gly
100 105 110
Gln Asn Tyr Gly Gly Ser Gln Gly Asn Leu Ile Phe Gly Lys Gly Thr
115 120 125
Lys Leu Ser Val Lys Pro Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr
130 135 140
Gln Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr
145 150 155 160
Asp Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr
165 170 175
Phe Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys
180 185 190
Ser Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln
195 200 205
Asp Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro
210 215 220
Cys Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu
225 230 235 240
Asn Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys
245 250 255
Val Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser Arg
260 265 270
Ala Lys Arg Ser Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln
275 280 285
Ala Gly Asp Val Glu Glu Asn Pro Gly Pro Met His Thr Trp Leu Val
290 295 300
Cys Trp Ala Ile Phe Ser Leu Leu Lys Ala Gly Leu Thr Glu Pro Glu
305 310 315 320
Val Thr Gln Thr Pro Ser His Gln Val Thr Gln Met Gly Gln Glu Val
325 330 335
Ile Leu Arg Cys Val Pro Ile Ser Asn His Leu Tyr Phe Tyr Trp Tyr
340 345 350
Arg Gln Ile Leu Gly Gln Lys Val Glu Phe Leu Val Ser Phe Tyr Asn
355 360 365
Asn Glu Ile Ser Glu Lys Ser Glu Ile Phe Asp Asp Gln Phe Ser Val
370 375 380
Glu Arg Pro Asp Gly Ser Asn Phe Thr Leu Lys Ile Arg Ser Thr Lys
385 390 395 400
Leu Glu Asp Ser Ala Met Tyr Phe Cys Ala Ser Arg Asp Pro Ala Tyr
405 410 415
Glu Gln Tyr Phe Gly Pro Gly Thr Arg Leu Thr Val Thr Glu Asp Leu
420 425 430
Arg Asn Val Thr Pro Pro Lys Val Ser Leu Phe Glu Pro Ser Lys Ala
435 440 445
Glu Ile Ala Asn Lys Gln Lys Ala Thr Leu Val Cys Leu Ala Arg Gly
450 455 460
Phe Phe Pro Asp His Val Glu Leu Ser Trp Trp Val Asn Gly Lys Glu
465 470 475 480
Val His Ser Gly Val Cys Thr Asp Pro Gln Ala Tyr Lys Glu Ser Asn
485 490 495
Tyr Ser Tyr Cys Leu Ser Ser Arg Leu Arg Val Ser Ala Thr Phe Trp
500 505 510
His Asn Pro Arg Asn His Phe Arg Cys Gln Val Gln Phe His Gly Leu
515 520 525
Ser Glu Glu Asp Lys Trp Pro Glu Gly Ser Pro Lys Pro Val Thr Gln
530 535 540
Asn Ile Ser Ala Glu Ala Trp Gly Arg Ala Asp Cys Gly Ile Thr Ser
545 550 555 560
Ala Ser Tyr Gln Gln Gly Val Leu Ser Ala Thr Ile Leu Tyr Glu Ile
565 570 575
Leu Leu Gly Lys Ala Thr Leu Tyr Ala Val Leu Val Ser Thr Leu Val
580 585 590
Val Met Ala Met Val Lys Arg Lys Asn Ser
595 600
<210> 562
<211> 606
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 562
Met Ala Ser Leu Arg Val Leu Leu Val Ile Leu Trp Leu Gln Leu Ser
1 5 10 15
Trp Val Trp Ser Gln Gln Lys Glu Val Glu Gln Asn Ser Gly Pro Leu
20 25 30
Ser Val Pro Glu Gly Ala Ile Ala Ser Leu Asn Cys Thr Tyr Ser Asp
35 40 45
Arg Gly Ser Gln Ser Phe Phe Trp Tyr Arg Gln Tyr Ser Gly Lys Ser
50 55 60
Pro Glu Leu Ile Met Phe Ile Tyr Ser Asn Gly Asp Lys Glu Asp Gly
65 70 75 80
Arg Phe Thr Ala Gln Leu Asn Lys Ala Ser Gln Tyr Val Ser Leu Leu
85 90 95
Ile Arg Asp Ser Gln Pro Ser Asp Ser Ala Thr Tyr Leu Cys Ala Val
100 105 110
Asn Pro Pro Val Lys Thr Ser Tyr Asp Lys Val Ile Phe Gly Pro Gly
115 120 125
Thr Ser Leu Ser Val Ile Pro Asn Ile Gln Asn Pro Glu Pro Ala Val
130 135 140
Tyr Gln Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe
145 150 155 160
Thr Asp Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly
165 170 175
Thr Phe Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser
180 185 190
Lys Ser Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys
195 200 205
Gln Asp Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val
210 215 220
Pro Cys Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn
225 230 235 240
Leu Asn Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu
245 250 255
Lys Val Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser
260 265 270
Arg Ala Lys Arg Ser Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys
275 280 285
Gln Ala Gly Asp Val Glu Glu Asn Pro Gly Pro Met His Thr Ser Leu
290 295 300
Leu Cys Trp Val Val Leu Gly Phe Leu Gly Thr Asp His Thr Gly Ala
305 310 315 320
Gly Val Ser Gln Ser Pro Arg Tyr Lys Val Thr Lys Arg Gly Gln Asp
325 330 335
Val Ala Leu Arg Cys Asp Pro Ile Ser Gly His Val Ser Leu Tyr Trp
340 345 350
Tyr Arg Gln Ala Leu Gly Gln Gly Pro Glu Phe Leu Thr Tyr Phe Asn
355 360 365
Tyr Glu Ala Gln Gln Asp Lys Ser Gly Leu Pro Asn Asp Arg Phe Ser
370 375 380
Ala Glu Arg Pro Glu Gly Ser Ile Ser Thr Leu Thr Ile Gln Arg Thr
385 390 395 400
Glu Gln Arg Asp Ser Ala Met Tyr Arg Cys Ala Ser Ser His Arg Glu
405 410 415
Pro His Thr Gly Glu Leu Phe Phe Gly Glu Gly Ser Arg Leu Thr Val
420 425 430
Leu Glu Asp Leu Arg Asn Val Thr Pro Pro Lys Val Ser Leu Phe Glu
435 440 445
Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys Ala Thr Leu Val Cys
450 455 460
Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu Leu Ser Trp Trp Val
465 470 475 480
Asn Gly Lys Glu Val His Ser Gly Val Cys Thr Asp Pro Gln Ala Tyr
485 490 495
Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser Arg Leu Arg Val Ser
500 505 510
Ala Thr Phe Trp His Asn Pro Arg Asn His Phe Arg Cys Gln Val Gln
515 520 525
Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro Glu Gly Ser Pro Lys
530 535 540
Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp Gly Arg Ala Asp Cys
545 550 555 560
Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val Leu Ser Ala Thr Ile
565 570 575
Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu Tyr Ala Val Leu Val
580 585 590
Ser Thr Leu Val Val Met Ala Met Val Lys Arg Lys Asn Ser
595 600 605
<210> 563
<211> 600
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 563
Met Ala Ser Leu Arg Val Leu Leu Val Ile Leu Trp Leu Gln Leu Ser
1 5 10 15
Trp Val Trp Ser Gln Gln Lys Glu Val Glu Gln Asn Ser Gly Pro Leu
20 25 30
Ser Val Pro Glu Gly Ala Ile Ala Ser Leu Asn Cys Thr Tyr Ser Asp
35 40 45
Arg Gly Ser Gln Ser Phe Phe Trp Tyr Arg Gln Tyr Ser Gly Lys Ser
50 55 60
Pro Glu Leu Ile Met Phe Ile Tyr Ser Asn Gly Asp Lys Glu Asp Gly
65 70 75 80
Arg Phe Thr Ala Gln Leu Asn Lys Ala Ser Gln Tyr Val Ser Leu Leu
85 90 95
Ile Arg Asp Ser Gln Pro Ser Asp Ser Ala Thr Tyr Leu Cys Ala Val
100 105 110
Thr Leu Cys Gly Gly Tyr Asn Lys Leu Ile Phe Gly Ala Gly Thr Arg
115 120 125
Leu Ala Val His Pro Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr Gln
130 135 140
Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr Asp
145 150 155 160
Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr Phe
165 170 175
Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys Ser
180 185 190
Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln Asp
195 200 205
Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro Cys
210 215 220
Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu Asn
225 230 235 240
Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys Val
245 250 255
Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser Arg Ala
260 265 270
Lys Arg Ser Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln Ala
275 280 285
Gly Asp Val Glu Glu Asn Pro Gly Pro Met His Asn Gln Val Leu Cys
290 295 300
Cys Val Val Leu Cys Phe Leu Gly Ala Asn Thr Val Asp Gly Gly Ile
305 310 315 320
Thr Gln Ser Pro Lys Tyr Leu Phe Arg Lys Glu Gly Gln Asn Val Thr
325 330 335
Leu Ser Cys Glu Gln Asn Leu Asn His Asp Ala Met Tyr Trp Tyr Arg
340 345 350
Gln Asp Pro Gly Gln Gly Leu Arg Leu Ile Tyr Tyr Ser Gln Ile Val
355 360 365
Asn Asp Phe Gln Lys Gly Asp Ile Val Glu Gly Tyr Ser Val Ser Arg
370 375 380
Glu Lys Lys Glu Ser Phe Pro Leu Thr Val Thr Ser Ala Gln Lys Asn
385 390 395 400
Pro Thr Ala Phe Tyr Leu Cys Ala Ser Ser Ser Arg Asp Tyr Glu Gln
405 410 415
Tyr Phe Gly Pro Gly Thr Arg Leu Thr Val Thr Glu Asp Leu Arg Asn
420 425 430
Val Thr Pro Pro Lys Val Ser Leu Phe Glu Pro Ser Lys Ala Glu Ile
435 440 445
Ala Asn Lys Gln Lys Ala Thr Leu Val Cys Leu Ala Arg Gly Phe Phe
450 455 460
Pro Asp His Val Glu Leu Ser Trp Trp Val Asn Gly Lys Glu Val His
465 470 475 480
Ser Gly Val Cys Thr Asp Pro Gln Ala Tyr Lys Glu Ser Asn Tyr Ser
485 490 495
Tyr Cys Leu Ser Ser Arg Leu Arg Val Ser Ala Thr Phe Trp His Asn
500 505 510
Pro Arg Asn His Phe Arg Cys Gln Val Gln Phe His Gly Leu Ser Glu
515 520 525
Glu Asp Lys Trp Pro Glu Gly Ser Pro Lys Pro Val Thr Gln Asn Ile
530 535 540
Ser Ala Glu Ala Trp Gly Arg Ala Asp Cys Gly Ile Thr Ser Ala Ser
545 550 555 560
Tyr Gln Gln Gly Val Leu Ser Ala Thr Ile Leu Tyr Glu Ile Leu Leu
565 570 575
Gly Lys Ala Thr Leu Tyr Ala Val Leu Val Ser Thr Leu Val Val Met
580 585 590
Ala Met Val Lys Arg Lys Asn Ser
595 600
<210> 564
<211> 600
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 564
Met Ala Ser Leu Arg Val Leu Leu Val Ile Leu Trp Leu Gln Leu Ser
1 5 10 15
Trp Val Trp Ser Gln Gln Lys Glu Val Glu Gln Asn Ser Gly Pro Leu
20 25 30
Ser Val Pro Glu Gly Ala Ile Ala Ser Leu Asn Cys Thr Tyr Ser Asp
35 40 45
Arg Gly Ser Gln Ser Phe Phe Trp Tyr Arg Gln Tyr Ser Gly Lys Ser
50 55 60
Pro Glu Leu Ile Met Phe Ile Tyr Ser Asn Gly Asp Lys Glu Asp Gly
65 70 75 80
Arg Phe Thr Ala Gln Leu Asn Lys Ala Ser Gln Tyr Val Ser Leu Leu
85 90 95
Ile Arg Asp Ser Gln Pro Ser Asp Ser Ala Thr Tyr Leu Cys Ala Val
100 105 110
Thr Leu Ser Gly Gly Tyr Asn Lys Leu Ile Phe Gly Ala Gly Thr Arg
115 120 125
Leu Ala Val His Pro Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr Gln
130 135 140
Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr Asp
145 150 155 160
Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr Phe
165 170 175
Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys Ser
180 185 190
Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln Asp
195 200 205
Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro Cys
210 215 220
Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu Asn
225 230 235 240
Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys Val
245 250 255
Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser Arg Ala
260 265 270
Lys Arg Ser Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln Ala
275 280 285
Gly Asp Val Glu Glu Asn Pro Gly Pro Met His Asn Gln Val Leu Cys
290 295 300
Cys Val Val Leu Cys Phe Leu Gly Ala Asn Thr Val Asp Gly Gly Ile
305 310 315 320
Thr Gln Ser Pro Lys Tyr Leu Phe Arg Lys Glu Gly Gln Asn Val Thr
325 330 335
Leu Ser Cys Glu Gln Asn Leu Asn His Asp Ala Met Tyr Trp Tyr Arg
340 345 350
Gln Asp Pro Gly Gln Gly Leu Arg Leu Ile Tyr Tyr Ser Gln Ile Val
355 360 365
Asn Asp Phe Gln Lys Gly Asp Ile Val Glu Gly Tyr Ser Val Ser Arg
370 375 380
Glu Lys Lys Glu Ser Phe Pro Leu Thr Val Thr Ser Ala Gln Lys Asn
385 390 395 400
Pro Thr Ala Phe Tyr Leu Cys Ala Ser Ser Ser Arg Asp Tyr Glu Gln
405 410 415
Tyr Phe Gly Pro Gly Thr Arg Leu Thr Val Thr Glu Asp Leu Arg Asn
420 425 430
Val Thr Pro Pro Lys Val Ser Leu Phe Glu Pro Ser Lys Ala Glu Ile
435 440 445
Ala Asn Lys Gln Lys Ala Thr Leu Val Cys Leu Ala Arg Gly Phe Phe
450 455 460
Pro Asp His Val Glu Leu Ser Trp Trp Val Asn Gly Lys Glu Val His
465 470 475 480
Ser Gly Val Cys Thr Asp Pro Gln Ala Tyr Lys Glu Ser Asn Tyr Ser
485 490 495
Tyr Cys Leu Ser Ser Arg Leu Arg Val Ser Ala Thr Phe Trp His Asn
500 505 510
Pro Arg Asn His Phe Arg Cys Gln Val Gln Phe His Gly Leu Ser Glu
515 520 525
Glu Asp Lys Trp Pro Glu Gly Ser Pro Lys Pro Val Thr Gln Asn Ile
530 535 540
Ser Ala Glu Ala Trp Gly Arg Ala Asp Cys Gly Ile Thr Ser Ala Ser
545 550 555 560
Tyr Gln Gln Gly Val Leu Ser Ala Thr Ile Leu Tyr Glu Ile Leu Leu
565 570 575
Gly Lys Ala Thr Leu Tyr Ala Val Leu Val Ser Thr Leu Val Val Met
580 585 590
Ala Met Val Lys Arg Lys Asn Ser
595 600
<210> 565
<211> 600
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 565
Met Ala Ser Ala Pro Ile Ser Met Leu Ala Met Leu Phe Thr Leu Ser
1 5 10 15
Gly Leu Arg Ala Gln Ser Val Ala Gln Pro Glu Asp Gln Val Asn Val
20 25 30
Ala Glu Gly Asn Pro Leu Thr Val Lys Cys Thr Tyr Ser Val Ser Gly
35 40 45
Asn Pro Tyr Leu Phe Trp Tyr Val Gln Tyr Pro Asn Arg Gly Leu Gln
50 55 60
Phe Leu Leu Lys Tyr Ile Thr Gly Asp Asn Leu Val Lys Gly Ser Tyr
65 70 75 80
Gly Phe Glu Ala Glu Phe Asn Lys Ser Gln Thr Ser Phe His Leu Lys
85 90 95
Lys Pro Ser Ala Leu Val Ser Asp Ser Ala Leu Tyr Phe Cys Ala Val
100 105 110
Arg Val Trp Asp Tyr Lys Leu Ser Phe Gly Ala Gly Thr Thr Val Thr
115 120 125
Val Arg Ala Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr Gln Leu Lys
130 135 140
Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr Asp Phe Asp
145 150 155 160
Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr Phe Ile Thr
165 170 175
Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys Ser Asn Gly
180 185 190
Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln Asp Ile Phe
195 200 205
Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro Cys Asp Ala
210 215 220
Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu Asn Phe Gln
225 230 235 240
Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys Val Ala Gly
245 250 255
Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser Arg Ala Lys Arg
260 265 270
Ser Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln Ala Gly Asp
275 280 285
Val Glu Glu Asn Pro Gly Pro Met His Asn Gln Val Leu Cys Cys Val
290 295 300
Val Leu Cys Phe Leu Gly Ala Asn Thr Val Asp Gly Gly Ile Thr Gln
305 310 315 320
Ser Pro Lys Tyr Leu Phe Arg Lys Glu Gly Gln Asn Val Thr Leu Ser
325 330 335
Cys Glu Gln Asn Leu Asn His Asp Ala Met Tyr Trp Tyr Arg Gln Asp
340 345 350
Pro Gly Gln Gly Leu Arg Leu Ile Tyr Tyr Ser Gln Ile Val Asn Asp
355 360 365
Phe Gln Lys Gly Asp Ile Ala Glu Gly Tyr Ser Val Ser Arg Glu Lys
370 375 380
Lys Glu Ser Phe Pro Leu Thr Val Thr Ser Ala Gln Lys Asn Pro Thr
385 390 395 400
Ala Phe Tyr Leu Cys Ala Ser Ser Ile Ser Ala Gly Gly Asp Gly Tyr
405 410 415
Thr Phe Gly Ser Gly Thr Arg Leu Thr Val Val Glu Asp Leu Arg Asn
420 425 430
Val Thr Pro Pro Lys Val Ser Leu Phe Glu Pro Ser Lys Ala Glu Ile
435 440 445
Ala Asn Lys Gln Lys Ala Thr Leu Val Cys Leu Ala Arg Gly Phe Phe
450 455 460
Pro Asp His Val Glu Leu Ser Trp Trp Val Asn Gly Lys Glu Val His
465 470 475 480
Ser Gly Val Cys Thr Asp Pro Gln Ala Tyr Lys Glu Ser Asn Tyr Ser
485 490 495
Tyr Cys Leu Ser Ser Arg Leu Arg Val Ser Ala Thr Phe Trp His Asn
500 505 510
Pro Arg Asn His Phe Arg Cys Gln Val Gln Phe His Gly Leu Ser Glu
515 520 525
Glu Asp Lys Trp Pro Glu Gly Ser Pro Lys Pro Val Thr Gln Asn Ile
530 535 540
Ser Ala Glu Ala Trp Gly Arg Ala Asp Cys Gly Ile Thr Ser Ala Ser
545 550 555 560
Tyr Gln Gln Gly Val Leu Ser Ala Thr Ile Leu Tyr Glu Ile Leu Leu
565 570 575
Gly Lys Ala Thr Leu Tyr Ala Val Leu Val Ser Thr Leu Val Val Met
580 585 590
Ala Met Val Lys Arg Lys Asn Ser
595 600
<210> 566
<211> 608
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 566
Met Ala Met Leu Leu Gly Ala Ser Val Leu Ile Leu Trp Leu Gln Pro
1 5 10 15
Asp Trp Val Asn Ser Gln Gln Lys Asn Asp Asp Gln Gln Val Lys Gln
20 25 30
Asn Ser Pro Ser Leu Ser Val Gln Glu Gly Arg Ile Ser Ile Leu Asn
35 40 45
Cys Asp Tyr Thr Asn Ser Met Phe Asp Tyr Phe Leu Trp Tyr Lys Lys
50 55 60
Tyr Pro Ala Glu Gly Pro Thr Phe Leu Ile Ser Ile Ser Ser Ile Lys
65 70 75 80
Asp Lys Asn Glu Asp Gly Arg Phe Thr Val Phe Leu Asn Lys Ser Ala
85 90 95
Lys His Leu Ser Leu His Ile Val Pro Ser Gln Pro Gly Asp Ser Ala
100 105 110
Val Tyr Phe Cys Ala Ala Asn Thr Gly Asn Gln Phe Tyr Phe Gly Thr
115 120 125
Gly Thr Ser Leu Thr Val Ile Pro Asn Ile Gln Asn Pro Glu Pro Ala
130 135 140
Val Tyr Gln Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu
145 150 155 160
Phe Thr Asp Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser
165 170 175
Gly Thr Phe Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp
180 185 190
Ser Lys Ser Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr
195 200 205
Cys Gln Asp Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp
210 215 220
Val Pro Cys Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met
225 230 235 240
Asn Leu Asn Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu
245 250 255
Leu Lys Val Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser
260 265 270
Ser Arg Ala Lys Arg Ser Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu
275 280 285
Lys Gln Ala Gly Asp Val Glu Glu Asn Pro Gly Pro Met His Thr Arg
290 295 300
Leu Leu Cys Trp Ala Ala Leu Cys Leu Leu Gly Ala Glu Leu Thr Glu
305 310 315 320
Ala Gly Val Ala Gln Ser Pro Arg Tyr Lys Ile Ile Glu Lys Arg Gln
325 330 335
Ser Val Ala Phe Trp Cys Asn Pro Ile Ser Gly His Ala Thr Leu Tyr
340 345 350
Trp Tyr Gln Gln Ile Leu Gly Gln Gly Pro Lys Leu Leu Ile Gln Phe
355 360 365
Gln Asn Asn Gly Val Val Asp Asp Ser Gln Leu Pro Lys Asp Arg Phe
370 375 380
Ser Ala Glu Arg Leu Lys Gly Val Asp Ser Thr Leu Lys Ile Gln Pro
385 390 395 400
Ala Lys Leu Glu Asp Ser Ala Val Tyr Leu Cys Ala Ser Ser His Leu
405 410 415
Ala Gly Glu Phe Tyr Asn Glu Gln Phe Phe Gly Pro Gly Thr Arg Leu
420 425 430
Thr Val Leu Glu Asp Leu Arg Asn Val Thr Pro Pro Lys Val Ser Leu
435 440 445
Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys Ala Thr Leu
450 455 460
Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu Leu Ser Trp
465 470 475 480
Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr Asp Pro Gln
485 490 495
Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser Arg Leu Arg
500 505 510
Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe Arg Cys Gln
515 520 525
Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro Glu Gly Ser
530 535 540
Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp Gly Arg Ala
545 550 555 560
Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val Leu Ser Ala
565 570 575
Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu Tyr Ala Val
580 585 590
Leu Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg Lys Asn Ser
595 600 605
<210> 567
<211> 595
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 567
Met Ala Gly Ala Phe Leu Leu Tyr Val Ser Met Lys Met Gly Gly Thr
1 5 10 15
Ala Gly Gln Ser Leu Glu Gln Pro Ser Glu Val Thr Ala Val Glu Gly
20 25 30
Ala Ile Val Gln Ile Asn Cys Thr Tyr Gln Thr Ser Gly Phe Tyr Gly
35 40 45
Leu Ser Trp Tyr Gln Gln His Asp Gly Gly Ala Pro Thr Phe Leu Ser
50 55 60
Tyr Asn Ala Leu Asp Gly Leu Glu Glu Thr Gly Arg Phe Ser Ser Phe
65 70 75 80
Leu Ser Arg Ser Asp Ser Tyr Gly Tyr Leu Leu Leu Gln Glu Leu Gln
85 90 95
Met Lys Asp Ser Ala Ser Tyr Phe Cys Ala Phe Ala Tyr Gly Gln Asn
100 105 110
Phe Val Phe Gly Pro Gly Thr Arg Leu Ser Val Leu Pro Asn Ile Gln
115 120 125
Asn Pro Glu Pro Ala Val Tyr Gln Leu Lys Asp Pro Arg Ser Gln Asp
130 135 140
Ser Thr Leu Cys Leu Phe Thr Asp Phe Asp Ser Gln Ile Asn Val Pro
145 150 155 160
Lys Thr Met Glu Ser Gly Thr Phe Ile Thr Asp Lys Cys Val Leu Asp
165 170 175
Met Lys Ala Met Asp Ser Lys Ser Asn Gly Ala Ile Ala Trp Ser Asn
180 185 190
Gln Thr Ser Phe Thr Cys Gln Asp Ile Phe Lys Glu Thr Asn Ala Thr
195 200 205
Tyr Pro Ser Ser Asp Val Pro Cys Asp Ala Thr Leu Thr Glu Lys Ser
210 215 220
Phe Glu Thr Asp Met Asn Leu Asn Phe Gln Asn Leu Leu Val Ile Val
225 230 235 240
Leu Arg Ile Leu Leu Leu Lys Val Ala Gly Phe Asn Leu Leu Met Thr
245 250 255
Leu Arg Leu Trp Ser Ser Arg Ala Lys Arg Ser Gly Ser Gly Ala Thr
260 265 270
Asn Phe Ser Leu Leu Lys Gln Ala Gly Asp Val Glu Glu Asn Pro Gly
275 280 285
Pro Met His Phe Arg Leu Leu Cys Cys Val Ala Phe Cys Leu Leu Gly
290 295 300
Ala Gly Pro Val Asp Ser Gly Val Thr Gln Thr Pro Lys His Leu Ile
305 310 315 320
Thr Ala Thr Gly Gln Arg Val Thr Leu Arg Cys Ser Pro Arg Ser Gly
325 330 335
Asp Leu Ser Val Tyr Trp Tyr Gln Gln Ser Leu Asp Gln Gly Leu Gln
340 345 350
Phe Leu Ile Gln Tyr Tyr Asn Gly Glu Glu Arg Ala Lys Gly Asn Ile
355 360 365
Leu Glu Arg Phe Ser Ala Gln Gln Phe Pro Asp Leu His Ser Glu Leu
370 375 380
Asn Leu Ser Ser Leu Glu Leu Gly Asp Ser Ala Leu Tyr Phe Cys Ala
385 390 395 400
Ser Ser Pro Leu Gly Asp Ser Gly Asn Thr Ile Tyr Phe Gly Glu Gly
405 410 415
Ser Trp Leu Thr Val Val Glu Asp Leu Arg Asn Val Thr Pro Pro Lys
420 425 430
Val Ser Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys
435 440 445
Ala Thr Leu Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu
450 455 460
Leu Ser Trp Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr
465 470 475 480
Asp Pro Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser
485 490 495
Arg Leu Arg Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe
500 505 510
Arg Cys Gln Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro
515 520 525
Glu Gly Ser Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp
530 535 540
Gly Arg Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val
545 550 555 560
Leu Ser Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu
565 570 575
Tyr Ala Val Leu Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg
580 585 590
Lys Asn Ser
595
<210> 568
<211> 599
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 568
Met Ala Thr Leu Leu Gly Val Ser Leu Val Ile Leu Trp Leu Gln Leu
1 5 10 15
Ala Arg Val Asn Ser Gln Gln Gly Glu Glu Asp Pro Gln Ala Leu Ser
20 25 30
Ile Gln Glu Gly Glu Asn Ala Thr Met Asn Cys Ser Tyr Lys Thr Ser
35 40 45
Ile Asn Asn Leu Gln Trp Tyr Arg Gln Asn Ser Gly Arg Gly Leu Val
50 55 60
His Leu Ile Leu Ile Arg Ser Asn Glu Arg Glu Lys His Ser Gly Arg
65 70 75 80
Leu Arg Val Thr Leu Asp Thr Ser Lys Lys Ser Ser Ser Leu Leu Ile
85 90 95
Thr Ala Ser Arg Ala Ala Asp Thr Ala Ser Tyr Phe Cys Ala Thr Asp
100 105 110
Ala Trp Asn Asn Asp Met Arg Phe Gly Ala Gly Thr Arg Leu Thr Val
115 120 125
Lys Pro Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr Gln Leu Lys Asp
130 135 140
Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr Asp Phe Asp Ser
145 150 155 160
Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr Phe Ile Thr Asp
165 170 175
Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys Ser Asn Gly Ala
180 185 190
Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln Asp Ile Phe Lys
195 200 205
Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro Cys Asp Ala Thr
210 215 220
Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu Asn Phe Gln Asn
225 230 235 240
Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys Val Ala Gly Phe
245 250 255
Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser Arg Ala Lys Arg Ser
260 265 270
Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln Ala Gly Asp Val
275 280 285
Glu Glu Asn Pro Gly Pro Met His Ile Gly Leu Leu Cys Cys Val Ala
290 295 300
Phe Ser Leu Leu Trp Ala Ser Pro Val Asn Ala Gly Val Thr Gln Thr
305 310 315 320
Pro Lys Phe Gln Val Leu Lys Thr Gly Gln Ser Met Thr Leu Gln Cys
325 330 335
Ala Gln Asp Met Asn His Asn Ser Met Tyr Trp Tyr Arg Gln Asp Pro
340 345 350
Gly Met Gly Leu Arg Leu Ile Tyr Tyr Ser Ala Ser Glu Gly Thr Thr
355 360 365
Asp Lys Gly Glu Val Pro Asn Gly Tyr Asn Val Ser Arg Leu Asn Lys
370 375 380
Arg Glu Phe Ser Leu Arg Leu Glu Ser Ala Ala Pro Ser Gln Thr Ser
385 390 395 400
Val Tyr Phe Cys Ala Ser Ser Glu Ser Gln Gly Asn Thr Glu Ala Phe
405 410 415
Phe Gly Gln Gly Thr Arg Leu Thr Val Val Glu Asp Leu Arg Asn Val
420 425 430
Thr Pro Pro Lys Val Ser Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala
435 440 445
Asn Lys Gln Lys Ala Thr Leu Val Cys Leu Ala Arg Gly Phe Phe Pro
450 455 460
Asp His Val Glu Leu Ser Trp Trp Val Asn Gly Lys Glu Val His Ser
465 470 475 480
Gly Val Cys Thr Asp Pro Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr
485 490 495
Cys Leu Ser Ser Arg Leu Arg Val Ser Ala Thr Phe Trp His Asn Pro
500 505 510
Arg Asn His Phe Arg Cys Gln Val Gln Phe His Gly Leu Ser Glu Glu
515 520 525
Asp Lys Trp Pro Glu Gly Ser Pro Lys Pro Val Thr Gln Asn Ile Ser
530 535 540
Ala Glu Ala Trp Gly Arg Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr
545 550 555 560
Gln Gln Gly Val Leu Ser Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly
565 570 575
Lys Ala Thr Leu Tyr Ala Val Leu Val Ser Thr Leu Val Val Met Ala
580 585 590
Met Val Lys Arg Lys Asn Ser
595
<210> 569
<211> 601
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 569
Met Ala Lys His Leu Thr Thr Phe Leu Val Ile Leu Trp Leu Tyr Phe
1 5 10 15
Tyr Arg Gly Asn Gly Lys Asn Gln Val Glu Gln Ser Pro Gln Ser Leu
20 25 30
Ile Ile Leu Glu Gly Lys Asn Cys Thr Leu Gln Cys Asn Tyr Thr Val
35 40 45
Ser Pro Phe Ser Asn Leu Arg Trp Tyr Lys Gln Asp Thr Gly Arg Gly
50 55 60
Pro Val Ser Leu Thr Ile Met Thr Phe Ser Glu Asn Thr Lys Ser Asn
65 70 75 80
Gly Arg Tyr Thr Ala Thr Leu Asp Ala Asp Thr Lys Gln Ser Ser Leu
85 90 95
His Ile Thr Ala Ser Gln Leu Ser Asp Ser Ala Ser Tyr Ile Cys Val
100 105 110
Val Ser Ser Tyr Lys Ile Ile Phe Gly Thr Gly Thr Arg Leu His Val
115 120 125
Phe Pro Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr Gln Leu Lys Asp
130 135 140
Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr Asp Phe Asp Ser
145 150 155 160
Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr Phe Ile Thr Asp
165 170 175
Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys Ser Asn Gly Ala
180 185 190
Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln Asp Ile Phe Lys
195 200 205
Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro Cys Asp Ala Thr
210 215 220
Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu Asn Phe Gln Asn
225 230 235 240
Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys Val Ala Gly Phe
245 250 255
Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser Arg Ala Lys Arg Ser
260 265 270
Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln Ala Gly Asp Val
275 280 285
Glu Glu Asn Pro Gly Pro Met His Thr Arg Leu Leu Phe Trp Val Ala
290 295 300
Phe Cys Leu Leu Gly Ala Tyr His Thr Gly Ala Gly Val Ser Gln Ser
305 310 315 320
Pro Ser Asn Lys Val Thr Glu Lys Gly Lys Asp Val Glu Leu Arg Cys
325 330 335
Asp Pro Ile Ser Gly His Thr Ala Leu Tyr Trp Tyr Arg Gln Arg Leu
340 345 350
Gly Gln Gly Leu Glu Phe Leu Ile Tyr Phe Gln Gly Asn Ser Ala Pro
355 360 365
Asp Lys Ser Gly Leu Pro Ser Asp Arg Phe Ser Ala Glu Arg Thr Gly
370 375 380
Glu Ser Val Ser Thr Leu Thr Ile Gln Arg Thr Gln Gln Glu Asp Ser
385 390 395 400
Ala Val Tyr Leu Cys Ala Ser Ser Pro Ile Gln Gly Glu Asn Ser Pro
405 410 415
Leu His Phe Gly Asn Gly Thr Arg Leu Thr Val Thr Glu Asp Leu Arg
420 425 430
Asn Val Thr Pro Pro Lys Val Ser Leu Phe Glu Pro Ser Lys Ala Glu
435 440 445
Ile Ala Asn Lys Gln Lys Ala Thr Leu Val Cys Leu Ala Arg Gly Phe
450 455 460
Phe Pro Asp His Val Glu Leu Ser Trp Trp Val Asn Gly Lys Glu Val
465 470 475 480
His Ser Gly Val Cys Thr Asp Pro Gln Ala Tyr Lys Glu Ser Asn Tyr
485 490 495
Ser Tyr Cys Leu Ser Ser Arg Leu Arg Val Ser Ala Thr Phe Trp His
500 505 510
Asn Pro Arg Asn His Phe Arg Cys Gln Val Gln Phe His Gly Leu Ser
515 520 525
Glu Glu Asp Lys Trp Pro Glu Gly Ser Pro Lys Pro Val Thr Gln Asn
530 535 540
Ile Ser Ala Glu Ala Trp Gly Arg Ala Asp Cys Gly Ile Thr Ser Ala
545 550 555 560
Ser Tyr Gln Gln Gly Val Leu Ser Ala Thr Ile Leu Tyr Glu Ile Leu
565 570 575
Leu Gly Lys Ala Thr Leu Tyr Ala Val Leu Val Ser Thr Leu Val Val
580 585 590
Met Ala Met Val Lys Arg Lys Asn Ser
595 600
<210> 570
<211> 601
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 570
Met Ala Lys His Leu Thr Thr Phe Leu Val Ile Leu Trp Leu Tyr Phe
1 5 10 15
Tyr Arg Gly Asn Gly Lys Asn Gln Val Glu Gln Ser Pro Gln Ser Leu
20 25 30
Ile Ile Leu Glu Gly Lys Asn Cys Thr Leu Gln Cys Asn Tyr Thr Val
35 40 45
Ser Pro Phe Ser Asn Leu Arg Trp Tyr Lys Gln Asp Thr Gly Arg Gly
50 55 60
Pro Val Ser Leu Thr Ile Met Thr Phe Ser Glu Asn Thr Lys Ser Asn
65 70 75 80
Gly Arg Tyr Thr Ala Thr Leu Asp Ala Asp Thr Lys Gln Ser Ser Leu
85 90 95
His Ile Thr Ala Ser Gln Leu Ser Asp Ser Ala Ser Tyr Ile Cys Val
100 105 110
Val Ser Ser Tyr Lys Leu Ile Phe Gly Thr Gly Thr Arg Leu Gln Val
115 120 125
Phe Pro Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr Gln Leu Lys Asp
130 135 140
Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr Asp Phe Asp Ser
145 150 155 160
Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr Phe Ile Thr Asp
165 170 175
Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys Ser Asn Gly Ala
180 185 190
Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln Asp Ile Phe Lys
195 200 205
Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro Cys Asp Ala Thr
210 215 220
Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu Asn Phe Gln Asn
225 230 235 240
Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys Val Ala Gly Phe
245 250 255
Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser Arg Ala Lys Arg Ser
260 265 270
Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln Ala Gly Asp Val
275 280 285
Glu Glu Asn Pro Gly Pro Met His Thr Arg Leu Leu Phe Trp Val Ala
290 295 300
Phe Cys Leu Leu Gly Ala Tyr His Thr Gly Ala Gly Val Ser Gln Ser
305 310 315 320
Pro Ser Asn Lys Val Thr Glu Lys Gly Lys Asp Val Glu Leu Arg Cys
325 330 335
Asp Pro Ile Ser Gly His Thr Ala Leu Tyr Trp Tyr Arg Gln Arg Leu
340 345 350
Gly Gln Gly Leu Glu Phe Leu Ile Tyr Phe Gln Gly Asn Ser Ala Pro
355 360 365
Asp Lys Ser Gly Leu Pro Ser Asp Arg Phe Ser Ala Glu Arg Thr Gly
370 375 380
Glu Ser Val Ser Thr Leu Thr Ile Gln Arg Thr Gln Gln Glu Asp Ser
385 390 395 400
Ala Val Tyr Leu Cys Ala Ser Ser Pro Ile Gln Gly Glu Asn Ser Pro
405 410 415
Leu His Phe Gly Asn Gly Thr Arg Leu Thr Val Thr Glu Asp Leu Arg
420 425 430
Asn Val Thr Pro Pro Lys Val Ser Leu Phe Glu Pro Ser Lys Ala Glu
435 440 445
Ile Ala Asn Lys Gln Lys Ala Thr Leu Val Cys Leu Ala Arg Gly Phe
450 455 460
Phe Pro Asp His Val Glu Leu Ser Trp Trp Val Asn Gly Lys Glu Val
465 470 475 480
His Ser Gly Val Cys Thr Asp Pro Gln Ala Tyr Lys Glu Ser Asn Tyr
485 490 495
Ser Tyr Cys Leu Ser Ser Arg Leu Arg Val Ser Ala Thr Phe Trp His
500 505 510
Asn Pro Arg Asn His Phe Arg Cys Gln Val Gln Phe His Gly Leu Ser
515 520 525
Glu Glu Asp Lys Trp Pro Glu Gly Ser Pro Lys Pro Val Thr Gln Asn
530 535 540
Ile Ser Ala Glu Ala Trp Gly Arg Ala Asp Cys Gly Ile Thr Ser Ala
545 550 555 560
Ser Tyr Gln Gln Gly Val Leu Ser Ala Thr Ile Leu Tyr Glu Ile Leu
565 570 575
Leu Gly Lys Ala Thr Leu Tyr Ala Val Leu Val Ser Thr Leu Val Val
580 585 590
Met Ala Met Val Lys Arg Lys Asn Ser
595 600
<210> 571
<211> 595
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 571
Met Ala Leu Leu Leu Val Pro Ala Phe Gln Val Ile Phe Thr Leu Gly
1 5 10 15
Gly Thr Arg Ala Gln Ser Val Thr Gln Leu Asp Ser Gln Val Pro Val
20 25 30
Phe Glu Glu Ala Pro Val Glu Leu Arg Cys Asn Tyr Ser Ser Ser Val
35 40 45
Ser Val Tyr Leu Phe Trp Tyr Val Gln Tyr Pro Asn Gln Gly Leu Gln
50 55 60
Leu Leu Leu Lys Tyr Leu Ser Gly Ser Thr Leu Val Glu Ser Ile Asn
65 70 75 80
Gly Phe Glu Ala Glu Phe Asn Lys Ser Gln Thr Ser Phe His Leu Arg
85 90 95
Lys Pro Ser Val His Ile Ser Asp Thr Ala Glu Tyr Phe Cys Ala Val
100 105 110
Ser Lys Gly Thr Gly Ala Gln Lys Leu Val Phe Gly Gln Gly Thr Arg
115 120 125
Leu Thr Ile Asn Pro Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr Gln
130 135 140
Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr Asp
145 150 155 160
Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr Phe
165 170 175
Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys Ser
180 185 190
Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln Asp
195 200 205
Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro Cys
210 215 220
Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu Asn
225 230 235 240
Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys Val
245 250 255
Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser Arg Ala
260 265 270
Lys Arg Ser Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln Ala
275 280 285
Gly Asp Val Glu Glu Asn Pro Gly Pro Met His Asn Gln Val Leu Cys
290 295 300
Cys Val Val Leu Cys Phe Leu Gly Ala Asn Thr Val Asp Gly Gly Ile
305 310 315 320
Thr Gln Ser Pro Lys Tyr Leu Phe Arg Lys Glu Gly Gln Asn Val Thr
325 330 335
Leu Ser Cys Glu Gln Asn Leu Asn His Asp Ala Met Tyr Trp Tyr Arg
340 345 350
Gln Asp Pro Gly Gln Gly Leu Arg Leu Ile Tyr Tyr Ser Gln Ile Val
355 360 365
Asn Asp Phe Gln Lys Gly Asp Ile Ala Glu Gly Tyr Ser Val Ser Arg
370 375 380
Glu Lys Lys Glu Ser Phe Pro Leu Ile Val Thr Ser Ala Gln Lys Asn
385 390 395 400
Pro Thr Ala Ser Tyr Leu Cys Ala Ser Glu Ala Phe Phe Gly Gln Gly
405 410 415
Thr Arg Leu Thr Val Val Glu Asp Leu Arg Asn Val Thr Pro Pro Lys
420 425 430
Val Ser Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys
435 440 445
Ala Thr Leu Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu
450 455 460
Leu Ser Trp Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr
465 470 475 480
Asp Pro Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser
485 490 495
Arg Leu Arg Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn His Phe
500 505 510
Arg Cys Gln Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro
515 520 525
Glu Gly Ser Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp
530 535 540
Gly Arg Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val
545 550 555 560
Leu Ser Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu
565 570 575
Tyr Ala Val Leu Val Ser Thr Leu Val Val Met Ala Met Val Lys Arg
580 585 590
Lys Asn Ser
595
<210> 572
<211> 597
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 572
Met Ala Leu Val Thr Ser Ile Thr Val Leu Leu Ser Leu Gly Ile Met
1 5 10 15
Gly Asp Ala Lys Thr Thr Gln Pro Asn Ser Met Glu Ser Asn Glu Glu
20 25 30
Glu Pro Val His Leu Pro Cys Asn His Ser Thr Ile Ser Gly Thr Asp
35 40 45
Tyr Ile His Trp Tyr Arg Gln Leu Pro Ser Gln Gly Pro Glu Tyr Val
50 55 60
Ile His Gly Leu Thr Ser Asn Val Asn Asn Arg Met Ala Ser Leu Ala
65 70 75 80
Ile Ala Glu Asp Arg Lys Ser Ser Thr Leu Ile Leu His Arg Ala Thr
85 90 95
Leu Arg Asp Ala Ala Val Tyr Tyr Cys Ile Leu Ala Ser Gly Ala Gly
100 105 110
Ser Tyr Gln Leu Thr Phe Gly Lys Gly Thr Lys Leu Ser Val Ile Pro
115 120 125
Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr Gln Leu Lys Asp Pro Arg
130 135 140
Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr Asp Phe Asp Ser Gln Ile
145 150 155 160
Asn Val Pro Lys Thr Met Glu Ser Gly Thr Phe Ile Thr Asp Lys Cys
165 170 175
Val Leu Asp Met Lys Ala Met Asp Ser Lys Ser Asn Gly Ala Ile Ala
180 185 190
Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln Asp Ile Phe Lys Glu Thr
195 200 205
Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro Cys Asp Ala Thr Leu Thr
210 215 220
Glu Lys Ser Phe Glu Thr Asp Met Asn Leu Asn Phe Gln Asn Leu Leu
225 230 235 240
Val Ile Val Leu Arg Ile Leu Leu Leu Lys Val Ala Gly Phe Asn Leu
245 250 255
Leu Met Thr Leu Arg Leu Trp Ser Ser Arg Ala Lys Arg Ser Gly Ser
260 265 270
Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln Ala Gly Asp Val Glu Glu
275 280 285
Asn Pro Gly Pro Met His Cys Arg Leu Leu Cys Cys Val Val Phe Cys
290 295 300
Leu Leu Gln Ala Gly Pro Leu Asp Thr Ala Val Ser Gln Thr Pro Lys
305 310 315 320
Tyr Leu Val Thr Gln Met Gly Asn Asp Lys Ser Ile Lys Cys Glu Gln
325 330 335
Asn Leu Gly His Asp Thr Met Tyr Trp Tyr Lys Gln Asp Ser Lys Lys
340 345 350
Phe Leu Lys Ile Met Phe Ser Tyr Asn Asn Lys Glu Leu Ile Ile Asn
355 360 365
Glu Thr Val Pro Asn Arg Phe Ser Pro Lys Ser Pro Asp Lys Ala His
370 375 380
Leu Asn Leu His Ile Asn Ser Leu Glu Leu Gly Asp Ser Ala Val Tyr
385 390 395 400
Phe Cys Ala Ser Arg Thr Ile Gly Tyr Asn Thr Glu Ala Phe Phe Gly
405 410 415
Gln Gly Thr Arg Leu Thr Val Val Glu Asp Leu Arg Asn Val Thr Pro
420 425 430
Pro Lys Val Ser Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys
435 440 445
Gln Lys Ala Thr Leu Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His
450 455 460
Val Glu Leu Ser Trp Trp Val Asn Gly Lys Glu Val His Ser Gly Val
465 470 475 480
Cys Thr Asp Pro Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu
485 490 495
Ser Ser Arg Leu Arg Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn
500 505 510
His Phe Arg Cys Gln Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys
515 520 525
Trp Pro Glu Gly Ser Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu
530 535 540
Ala Trp Gly Arg Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln
545 550 555 560
Gly Val Leu Ser Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala
565 570 575
Thr Leu Tyr Ala Val Leu Val Ser Thr Leu Val Val Met Ala Met Val
580 585 590
Lys Arg Lys Asn Ser
595
<210> 573
<211> 602
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 573
Met Ala Lys Ile Arg Gln Phe Leu Leu Ala Ile Leu Trp Leu Gln Leu
1 5 10 15
Ser Cys Val Ser Ala Ala Lys Asn Glu Val Glu Gln Ser Pro Gln Asn
20 25 30
Leu Thr Ala Gln Glu Gly Glu Phe Ile Thr Ile Asn Cys Ser Tyr Ser
35 40 45
Val Gly Ile Ser Ala Leu His Trp Leu Gln Gln His Pro Gly Gly Gly
50 55 60
Ile Val Ser Leu Phe Met Leu Ser Ser Gly Lys Lys Lys His Gly Arg
65 70 75 80
Leu Ile Ala Thr Ile Asn Ile Gln Glu Lys His Ser Ser Leu His Ile
85 90 95
Thr Ala Ser His Pro Arg Asp Ser Ala Val Tyr Ile Cys Ala Ala Leu
100 105 110
Ser Tyr Asn Thr Asp Lys Leu Ile Phe Gly Thr Gly Thr Arg Leu Gln
115 120 125
Val Phe Pro Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr Gln Leu Lys
130 135 140
Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr Asp Phe Asp
145 150 155 160
Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr Phe Ile Thr
165 170 175
Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys Ser Asn Gly
180 185 190
Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln Asp Ile Phe
195 200 205
Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro Cys Asp Ala
210 215 220
Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu Asn Phe Gln
225 230 235 240
Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys Val Ala Gly
245 250 255
Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser Arg Ala Lys Arg
260 265 270
Ser Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln Ala Gly Asp
275 280 285
Val Glu Glu Asn Pro Gly Pro Met His Thr Arg Leu Leu Cys Trp Ala
290 295 300
Ala Leu Cys Leu Leu Gly Ala Asp His Thr Gly Ala Gly Val Ser Gln
305 310 315 320
Thr Pro Ser Asn Lys Val Thr Glu Lys Gly Lys Tyr Val Glu Leu Arg
325 330 335
Cys Asp Pro Ile Ser Gly His Thr Ala Leu Tyr Trp Tyr Arg Gln Ser
340 345 350
Leu Gly Gln Gly Pro Glu Phe Leu Ile Tyr Phe Gln Gly Thr Gly Ala
355 360 365
Ala Asp Asp Ser Gly Leu Pro Asn Asp Arg Phe Phe Ala Val Arg Pro
370 375 380
Glu Gly Ser Val Ser Thr Leu Lys Ile Gln Arg Thr Glu Arg Gly Asp
385 390 395 400
Ser Ala Val Tyr Leu Cys Ala Ser Ser Leu Ser Gly Leu Leu Gln Glu
405 410 415
Thr Gln Tyr Phe Gly Pro Gly Thr Arg Leu Leu Val Leu Glu Asp Leu
420 425 430
Arg Asn Val Thr Pro Pro Lys Val Ser Leu Phe Glu Pro Ser Lys Ala
435 440 445
Glu Ile Ala Asn Lys Gln Lys Ala Thr Leu Val Cys Leu Ala Arg Gly
450 455 460
Phe Phe Pro Asp His Val Glu Leu Ser Trp Trp Val Asn Gly Lys Glu
465 470 475 480
Val His Ser Gly Val Cys Thr Asp Pro Gln Ala Tyr Lys Glu Ser Asn
485 490 495
Tyr Ser Tyr Cys Leu Ser Ser Arg Leu Arg Val Ser Ala Thr Phe Trp
500 505 510
His Asn Pro Arg Asn His Phe Arg Cys Gln Val Gln Phe His Gly Leu
515 520 525
Ser Glu Glu Asp Lys Trp Pro Glu Gly Ser Pro Lys Pro Val Thr Gln
530 535 540
Asn Ile Ser Ala Glu Ala Trp Gly Arg Ala Asp Cys Gly Ile Thr Ser
545 550 555 560
Ala Ser Tyr Gln Gln Gly Val Leu Ser Ala Thr Ile Leu Tyr Glu Ile
565 570 575
Leu Leu Gly Lys Ala Thr Leu Tyr Ala Val Leu Val Ser Thr Leu Val
580 585 590
Val Met Ala Met Val Lys Arg Lys Asn Ser
595 600
<210> 574
<211> 605
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 574
Met Ala Tyr Ser Pro Gly Leu Val Ser Leu Ile Leu Leu Leu Leu Gly
1 5 10 15
Arg Thr Arg Gly Asn Ser Val Thr Gln Met Glu Gly Pro Val Thr Leu
20 25 30
Ser Glu Glu Ala Phe Leu Thr Ile Asn Cys Thr Tyr Thr Ala Thr Gly
35 40 45
Tyr Pro Ser Leu Phe Trp Tyr Val Gln Tyr Pro Gly Glu Gly Leu Gln
50 55 60
Leu Leu Leu Lys Ala Thr Lys Ala Asp Asp Lys Gly Ser Asn Lys Gly
65 70 75 80
Phe Glu Ala Thr Tyr Arg Lys Glu Thr Thr Ser Phe His Leu Glu Lys
85 90 95
Gly Ser Val Gln Val Ser Asp Ser Ala Val Tyr Phe Cys Ala Leu Ser
100 105 110
His Thr Gly Ser Ser Asn Thr Gly Lys Leu Ile Phe Gly Gln Gly Thr
115 120 125
Arg Leu Gln Val Lys Pro Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr
130 135 140
Gln Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr
145 150 155 160
Asp Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr
165 170 175
Phe Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys
180 185 190
Ser Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln
195 200 205
Asp Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro
210 215 220
Cys Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu
225 230 235 240
Asn Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys
245 250 255
Val Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser Arg
260 265 270
Ala Lys Arg Ser Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln
275 280 285
Ala Gly Asp Val Glu Glu Asn Pro Gly Pro Met His Thr Arg Leu Leu
290 295 300
Cys Trp Ala Ala Leu Cys Leu Leu Gly Ala Glu Leu Thr Glu Ala Gly
305 310 315 320
Val Ala Gln Ser Pro Arg Tyr Lys Ile Ile Glu Lys Arg Gln Ser Val
325 330 335
Ala Phe Trp Cys Asn Pro Ile Ser Gly His Ala Thr Leu Tyr Trp Tyr
340 345 350
Gln Gln Ile Leu Gly Gln Gly Pro Lys Leu Leu Ile Gln Phe Gln Asn
355 360 365
Asn Gly Val Val Asp Asp Ser Gln Leu Pro Lys Asp Arg Phe Ser Ala
370 375 380
Glu Arg Leu Lys Gly Val Asp Ser Thr Leu Lys Ile Gln Pro Ala Lys
385 390 395 400
Leu Glu Asp Ser Ala Val Tyr Leu Cys Ala Ser Ser Thr Gly Gly Gly
405 410 415
Arg His Gln Pro Gln His Phe Gly Asp Gly Thr Arg Leu Ser Ile Leu
420 425 430
Glu Asp Leu Arg Asn Val Thr Pro Pro Lys Val Ser Leu Phe Glu Pro
435 440 445
Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys Ala Thr Leu Val Cys Leu
450 455 460
Ala Arg Gly Phe Phe Pro Asp His Val Glu Leu Ser Trp Trp Val Asn
465 470 475 480
Gly Lys Glu Val His Ser Gly Val Cys Thr Asp Pro Gln Ala Tyr Lys
485 490 495
Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser Arg Leu Arg Val Ser Ala
500 505 510
Thr Phe Trp His Asn Pro Arg Asn His Phe Arg Cys Gln Val Gln Phe
515 520 525
His Gly Leu Ser Glu Glu Asp Lys Trp Pro Glu Gly Ser Pro Lys Pro
530 535 540
Val Thr Gln Asn Ile Ser Ala Glu Ala Trp Gly Arg Ala Asp Cys Gly
545 550 555 560
Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val Leu Ser Ala Thr Ile Leu
565 570 575
Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu Tyr Ala Val Leu Val Ser
580 585 590
Thr Leu Val Val Met Ala Met Val Lys Arg Lys Asn Ser
595 600 605
<210> 575
<211> 605
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 575
Met Ala Tyr Ser Pro Gly Leu Val Ser Leu Ile Leu Leu Leu Leu Gly
1 5 10 15
Arg Thr Arg Gly Asn Ser Val Thr Gln Met Glu Gly Pro Val Thr Leu
20 25 30
Ser Glu Glu Ala Phe Leu Thr Ile Asn Cys Thr Tyr Thr Ala Thr Gly
35 40 45
Tyr Pro Ser Leu Phe Trp Tyr Val Gln Tyr Pro Gly Glu Gly Leu Gln
50 55 60
Leu Leu Leu Lys Ala Thr Lys Ala Asp Asp Lys Gly Ser Asn Lys Gly
65 70 75 80
Phe Glu Ala Thr Tyr Arg Lys Glu Thr Thr Ser Phe His Leu Glu Lys
85 90 95
Gly Ser Val Gln Val Ser Asp Ser Ala Val Tyr Phe Cys Ala Leu Ser
100 105 110
Gln Thr Gly Ser Ser Lys Thr Gly Lys Leu Ile Phe Gly Gln Gly Thr
115 120 125
Arg Leu Gln Val Lys Pro Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr
130 135 140
Gln Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr
145 150 155 160
Asp Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr
165 170 175
Phe Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys
180 185 190
Ser Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln
195 200 205
Asp Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro
210 215 220
Cys Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu
225 230 235 240
Asn Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys
245 250 255
Val Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser Arg
260 265 270
Ala Lys Arg Ser Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln
275 280 285
Ala Gly Asp Val Glu Glu Asn Pro Gly Pro Met His Thr Arg Leu Leu
290 295 300
Cys Trp Ala Ala Leu Cys Leu Leu Gly Ala Glu Leu Thr Glu Ala Gly
305 310 315 320
Val Ala Gln Ser Pro Arg Tyr Lys Ile Ile Glu Lys Arg Gln Ser Val
325 330 335
Ala Phe Trp Cys Asn Pro Ile Ser Gly His Ala Thr Leu Tyr Trp Tyr
340 345 350
Gln Gln Ile Leu Gly Gln Gly Pro Lys Leu Leu Ile Gln Phe Gln Asn
355 360 365
Asn Gly Val Val Asp Asp Ser Gln Leu Pro Lys Asp Arg Phe Ser Ala
370 375 380
Glu Arg Leu Lys Gly Val Asp Ser Thr Leu Lys Ile Gln Pro Ala Lys
385 390 395 400
Leu Glu Asp Ser Ala Val Tyr Leu Cys Ala Ser Ser Thr Gly Gly Gly
405 410 415
Arg His Gln Pro Gln His Phe Gly Asp Gly Thr Arg Leu Ser Ile Leu
420 425 430
Glu Asp Leu Arg Asn Val Thr Pro Pro Lys Val Ser Leu Phe Glu Pro
435 440 445
Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys Ala Thr Leu Val Cys Leu
450 455 460
Ala Arg Gly Phe Phe Pro Asp His Val Glu Leu Ser Trp Trp Val Asn
465 470 475 480
Gly Lys Glu Val His Ser Gly Val Cys Thr Asp Pro Gln Ala Tyr Lys
485 490 495
Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser Arg Leu Arg Val Ser Ala
500 505 510
Thr Phe Trp His Asn Pro Arg Asn His Phe Arg Cys Gln Val Gln Phe
515 520 525
His Gly Leu Ser Glu Glu Asp Lys Trp Pro Glu Gly Ser Pro Lys Pro
530 535 540
Val Thr Gln Asn Ile Ser Ala Glu Ala Trp Gly Arg Ala Asp Cys Gly
545 550 555 560
Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val Leu Ser Ala Thr Ile Leu
565 570 575
Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu Tyr Ala Val Leu Val Ser
580 585 590
Thr Leu Val Val Met Ala Met Val Lys Arg Lys Asn Ser
595 600 605
<210> 576
<211> 605
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 576
Met Ala Tyr Ser Pro Gly Leu Val Ser Leu Ile Leu Leu Leu Leu Gly
1 5 10 15
Arg Thr Arg Gly Asn Ser Val Thr Gln Met Glu Gly Pro Val Thr Leu
20 25 30
Ser Glu Glu Ala Phe Leu Thr Ile Asn Cys Thr Tyr Thr Ala Thr Gly
35 40 45
Tyr Pro Ser Leu Phe Trp Tyr Val Gln Tyr Pro Gly Glu Gly Leu Gln
50 55 60
Leu Leu Leu Lys Ala Thr Lys Ala Asp Asp Lys Gly Ser Asn Lys Gly
65 70 75 80
Phe Glu Ala Thr Tyr Arg Lys Glu Thr Thr Ser Phe His Leu Glu Lys
85 90 95
Gly Ser Val Gln Val Ser Asp Ser Ala Val Tyr Phe Cys Ala Leu Ser
100 105 110
Gln Thr Gly Ser Ser Asn Thr Gly Lys Leu Ile Phe Gly Gln Gly Thr
115 120 125
Arg Leu Gln Val Lys Pro Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr
130 135 140
Gln Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr
145 150 155 160
Asp Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr
165 170 175
Phe Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys
180 185 190
Ser Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln
195 200 205
Asp Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro
210 215 220
Cys Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu
225 230 235 240
Asn Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys
245 250 255
Val Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser Arg
260 265 270
Ala Lys Arg Ser Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln
275 280 285
Ala Gly Asp Val Glu Glu Asn Pro Gly Pro Met His Thr Arg Leu Leu
290 295 300
Cys Trp Ala Ala Leu Cys Leu Leu Gly Ala Glu Leu Thr Glu Ala Gly
305 310 315 320
Val Ala Gln Ser Pro Arg Tyr Lys Ile Ile Glu Lys Arg Gln Ser Val
325 330 335
Ala Phe Trp Cys Asn Pro Ile Ser Gly His Ala Thr Leu Tyr Trp Tyr
340 345 350
Gln Gln Ile Leu Gly Gln Gly Pro Lys Leu Leu Ile Gln Phe Gln Asn
355 360 365
Asn Gly Val Val Asp Asp Ser Gln Leu Pro Lys Asp Arg Phe Ser Ala
370 375 380
Glu Arg Leu Lys Gly Val Asp Ser Thr Leu Lys Ile Gln Pro Ala Lys
385 390 395 400
Leu Glu Asp Ser Ala Val Tyr Leu Cys Ala Ser Ser Thr Gly Gly Gly
405 410 415
Arg His Gln Pro Gln His Phe Gly Asp Gly Thr Arg Leu Ser Ile Leu
420 425 430
Glu Asp Leu Arg Asn Val Thr Pro Pro Lys Val Ser Leu Phe Glu Pro
435 440 445
Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys Ala Thr Leu Val Cys Leu
450 455 460
Ala Arg Gly Phe Phe Pro Asp His Val Glu Leu Ser Trp Trp Val Asn
465 470 475 480
Gly Lys Glu Val His Ser Gly Val Cys Thr Asp Pro Gln Ala Tyr Lys
485 490 495
Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser Arg Leu Arg Val Ser Ala
500 505 510
Thr Phe Trp His Asn Pro Arg Asn His Phe Arg Cys Gln Val Gln Phe
515 520 525
His Gly Leu Ser Glu Glu Asp Lys Trp Pro Glu Gly Ser Pro Lys Pro
530 535 540
Val Thr Gln Asn Ile Ser Ala Glu Ala Trp Gly Arg Ala Asp Cys Gly
545 550 555 560
Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val Leu Ser Ala Thr Ile Leu
565 570 575
Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu Tyr Ala Val Leu Val Ser
580 585 590
Thr Leu Val Val Met Ala Met Val Lys Arg Lys Asn Ser
595 600 605
<210> 577
<211> 605
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 577
Met Ala Tyr Ser Pro Gly Leu Val Ser Leu Ile Leu Leu Leu Leu Gly
1 5 10 15
Arg Thr Arg Gly Asn Ser Val Thr Gln Met Glu Gly Pro Val Thr Leu
20 25 30
Ser Glu Glu Ala Phe Leu Thr Ile Asn Cys Thr Tyr Thr Ala Thr Gly
35 40 45
Tyr Pro Ser Leu Phe Trp Tyr Val Gln Tyr Pro Gly Glu Gly Leu Gln
50 55 60
Leu Leu Leu Lys Ala Thr Lys Ala Asp Asp Lys Gly Ser Asn Lys Gly
65 70 75 80
Phe Glu Ala Thr Tyr Arg Lys Glu Thr Thr Ser Phe His Leu Glu Lys
85 90 95
Gly Ser Val Gln Val Ser Asp Ser Ala Val Tyr Phe Cys Ala Leu Ser
100 105 110
Thr Thr Gly Ser Ser Asn Thr Gly Lys Leu Ile Phe Gly Gln Gly Thr
115 120 125
Thr Leu Gln Val Lys Pro Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr
130 135 140
Gln Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr
145 150 155 160
Asp Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr
165 170 175
Phe Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys
180 185 190
Ser Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln
195 200 205
Asp Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro
210 215 220
Cys Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu
225 230 235 240
Asn Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys
245 250 255
Val Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser Arg
260 265 270
Ala Lys Arg Ser Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln
275 280 285
Ala Gly Asp Val Glu Glu Asn Pro Gly Pro Met His Thr Arg Leu Leu
290 295 300
Cys Trp Ala Ala Leu Cys Leu Leu Gly Ala Glu Leu Thr Glu Ala Gly
305 310 315 320
Val Ala Gln Ser Pro Arg Tyr Lys Ile Ile Glu Lys Arg Gln Ser Val
325 330 335
Ala Phe Trp Cys Asn Pro Ile Ser Gly His Ala Thr Leu Tyr Trp Tyr
340 345 350
Gln Gln Ile Leu Gly Gln Gly Pro Lys Leu Leu Ile Gln Phe Gln Asn
355 360 365
Asn Gly Val Val Asp Asp Ser Gln Leu Pro Lys Asp Arg Phe Ser Ala
370 375 380
Glu Arg Leu Lys Gly Val Asp Ser Thr Leu Lys Ile Gln Pro Ala Lys
385 390 395 400
Leu Glu Asp Ser Ala Val Tyr Leu Cys Ala Ser Ser Thr Gly Gly Gly
405 410 415
Arg His Gln Pro Gln His Phe Gly Asp Gly Thr Arg Leu Ser Ile Leu
420 425 430
Glu Asp Leu Arg Asn Val Thr Pro Pro Lys Val Ser Leu Phe Glu Pro
435 440 445
Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys Ala Thr Leu Val Cys Leu
450 455 460
Ala Arg Gly Phe Phe Pro Asp His Val Glu Leu Ser Trp Trp Val Asn
465 470 475 480
Gly Lys Glu Val His Ser Gly Val Cys Thr Asp Pro Gln Ala Tyr Lys
485 490 495
Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser Arg Leu Arg Val Ser Ala
500 505 510
Thr Phe Trp His Asn Pro Arg Asn His Phe Arg Cys Gln Val Gln Phe
515 520 525
His Gly Leu Ser Glu Glu Asp Lys Trp Pro Glu Gly Ser Pro Lys Pro
530 535 540
Val Thr Gln Asn Ile Ser Ala Glu Ala Trp Gly Arg Ala Asp Cys Gly
545 550 555 560
Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val Leu Ser Ala Thr Ile Leu
565 570 575
Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu Tyr Ala Val Leu Val Ser
580 585 590
Thr Leu Val Val Met Ala Met Val Lys Arg Lys Asn Ser
595 600 605
<210> 578
<211> 598
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 578
Met Ala Ser Leu Arg Val Leu Leu Val Ile Leu Trp Leu Gln Leu Ser
1 5 10 15
Trp Val Trp Ser Gln Gln Lys Glu Val Glu Gln Asn Ser Gly Pro Leu
20 25 30
Ser Val Pro Glu Gly Ala Ile Ala Ser Leu Asn Cys Thr Tyr Ser Asp
35 40 45
Arg Gly Ser Gln Ser Phe Phe Trp Tyr Arg Gln Tyr Ser Gly Lys Ser
50 55 60
Pro Glu Leu Ile Met Phe Ile Tyr Ser Asn Gly Asp Lys Glu Asp Gly
65 70 75 80
Arg Phe Thr Ala Gln Leu Asn Lys Ala Ser Gln Tyr Val Ser Leu Leu
85 90 95
Ile Arg Asp Ser Gln Pro Ser Asp Ser Ala Thr Tyr Leu Cys Ala Val
100 105 110
Ser Trp Tyr Ser Thr Leu Thr Phe Gly Lys Gly Thr Met Leu Leu Val
115 120 125
Ser Pro Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr Gln Leu Lys Asp
130 135 140
Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr Asp Phe Asp Ser
145 150 155 160
Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr Phe Ile Thr Asp
165 170 175
Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys Ser Asn Gly Ala
180 185 190
Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln Asp Ile Phe Lys
195 200 205
Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro Cys Asp Ala Thr
210 215 220
Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu Asn Phe Gln Asn
225 230 235 240
Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys Val Ala Gly Phe
245 250 255
Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser Arg Ala Lys Arg Ser
260 265 270
Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln Ala Gly Asp Val
275 280 285
Glu Glu Asn Pro Gly Pro Met His Thr Arg Leu Phe Phe Tyr Val Ala
290 295 300
Leu Cys Leu Leu Trp Ala Gly His Arg Asp Ala Gly Ile Thr Gln Ser
305 310 315 320
Pro Arg Tyr Lys Ile Thr Glu Thr Gly Arg Gln Val Thr Leu Met Cys
325 330 335
His Gln Thr Trp Ser His Ser Tyr Met Phe Trp Tyr Arg Gln Asp Leu
340 345 350
Gly His Gly Leu Arg Leu Ile Tyr Tyr Ser Ala Ala Ala Asp Ile Thr
355 360 365
Asp Lys Gly Glu Val Pro Asp Gly Tyr Val Val Ser Arg Ser Lys Thr
370 375 380
Glu Asn Phe Pro Leu Thr Leu Glu Ser Ala Thr Arg Ser Gln Thr Ser
385 390 395 400
Val Tyr Phe Cys Ala Ser Ser Gly Ser Arg Thr Asp Thr Gln Tyr Phe
405 410 415
Gly Pro Gly Thr Arg Leu Thr Val Leu Glu Asp Leu Arg Asn Val Thr
420 425 430
Pro Pro Lys Val Ser Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn
435 440 445
Lys Gln Lys Ala Thr Leu Val Cys Leu Ala Arg Gly Phe Phe Pro Asp
450 455 460
His Val Glu Leu Ser Trp Trp Val Asn Gly Lys Glu Val His Ser Gly
465 470 475 480
Val Cys Thr Asp Pro Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys
485 490 495
Leu Ser Ser Arg Leu Arg Val Ser Ala Thr Phe Trp His Asn Pro Arg
500 505 510
Asn His Phe Arg Cys Gln Val Gln Phe His Gly Leu Ser Glu Glu Asp
515 520 525
Lys Trp Pro Glu Gly Ser Pro Lys Pro Val Thr Gln Asn Ile Ser Ala
530 535 540
Glu Ala Trp Gly Arg Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln
545 550 555 560
Gln Gly Val Leu Ser Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys
565 570 575
Ala Thr Leu Tyr Ala Val Leu Val Ser Thr Leu Val Val Met Ala Met
580 585 590
Val Lys Arg Lys Asn Ser
595
<210> 579
<211> 597
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 579
Met Ala Leu Lys Phe Ser Val Ser Ile Leu Trp Ile Gln Leu Ala Trp
1 5 10 15
Val Ser Thr Gln Leu Leu Glu Gln Ser Pro Gln Phe Leu Ser Ile Gln
20 25 30
Glu Gly Glu Asn Leu Thr Val Tyr Cys Asn Ser Ser Ser Val Phe Ser
35 40 45
Ser Leu Gln Trp Tyr Arg Gln Glu Pro Gly Glu Gly Pro Val Leu Leu
50 55 60
Val Thr Val Val Thr Gly Gly Glu Val Lys Lys Leu Lys Arg Leu Thr
65 70 75 80
Phe Gln Phe Gly Asp Ala Arg Lys Asp Ser Ser Leu His Ile Thr Ala
85 90 95
Ala Gln Pro Gly Asp Thr Gly Leu Tyr Leu Cys Ala Gly Glu Phe Ala
100 105 110
Gly Asn Gln Phe Tyr Phe Gly Thr Gly Thr Ser Leu Thr Val Ile Pro
115 120 125
Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr Gln Leu Lys Asp Pro Arg
130 135 140
Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr Asp Phe Asp Ser Gln Ile
145 150 155 160
Asn Val Pro Lys Thr Met Glu Ser Gly Thr Phe Ile Thr Asp Lys Cys
165 170 175
Val Leu Asp Met Lys Ala Met Asp Ser Lys Ser Asn Gly Ala Ile Ala
180 185 190
Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln Asp Ile Phe Lys Glu Thr
195 200 205
Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro Cys Asp Ala Thr Leu Thr
210 215 220
Glu Lys Ser Phe Glu Thr Asp Met Asn Leu Asn Phe Gln Asn Leu Leu
225 230 235 240
Val Ile Val Leu Arg Ile Leu Leu Leu Lys Val Ala Gly Phe Asn Leu
245 250 255
Leu Met Thr Leu Arg Leu Trp Ser Ser Arg Ala Lys Arg Ser Gly Ser
260 265 270
Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln Ala Gly Asp Val Glu Glu
275 280 285
Asn Pro Gly Pro Met His Cys Arg Leu Leu Cys Cys Ala Val Leu Cys
290 295 300
Leu Leu Gly Ala Val Pro Ile Asp Thr Glu Val Thr Gln Thr Pro Lys
305 310 315 320
His Leu Val Met Gly Met Thr Asn Lys Lys Ser Leu Lys Cys Glu Gln
325 330 335
His Met Gly His Arg Ala Met Tyr Trp Tyr Lys Gln Lys Ala Lys Lys
340 345 350
Pro Pro Glu Leu Met Phe Val Tyr Ser Tyr Glu Lys Leu Ser Ile Asn
355 360 365
Glu Ser Val Pro Ser Arg Phe Ser Pro Glu Cys Pro Asn Ser Ser Leu
370 375 380
Leu Asn Leu His Leu His Ala Leu Gln Pro Glu Asp Ser Ala Leu Tyr
385 390 395 400
Leu Cys Ala Ser Ser Gln Val Gly Leu Thr Tyr Glu Gln Tyr Phe Gly
405 410 415
Pro Gly Thr Arg Leu Thr Val Thr Glu Asp Leu Arg Asn Val Thr Pro
420 425 430
Pro Lys Val Ser Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys
435 440 445
Gln Lys Ala Thr Leu Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His
450 455 460
Val Glu Leu Ser Trp Trp Val Asn Gly Lys Glu Val His Ser Gly Val
465 470 475 480
Cys Thr Asp Pro Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu
485 490 495
Ser Ser Arg Leu Arg Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn
500 505 510
His Phe Arg Cys Gln Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys
515 520 525
Trp Pro Glu Gly Ser Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu
530 535 540
Ala Trp Gly Arg Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln
545 550 555 560
Gly Val Leu Ser Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala
565 570 575
Thr Leu Tyr Ala Val Leu Val Ser Thr Leu Val Val Met Ala Met Val
580 585 590
Lys Arg Lys Asn Ser
595
<210> 580
<211> 604
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 580
Met Ala Ser Ala Pro Ile Ser Met Leu Ala Met Leu Phe Thr Leu Ser
1 5 10 15
Gly Leu Arg Ala Gln Ser Val Ala Gln Pro Glu Asp Gln Val Asn Val
20 25 30
Ala Glu Gly Asn Pro Leu Thr Val Lys Cys Thr Tyr Ser Val Ser Gly
35 40 45
Asn Pro Tyr Leu Phe Trp Tyr Val Gln Tyr Pro Asn Arg Gly Leu Gln
50 55 60
Phe Leu Leu Lys Tyr Ile Thr Gly Asp Asn Leu Val Lys Gly Ser Tyr
65 70 75 80
Gly Phe Glu Ala Glu Phe Asn Lys Ser Gln Thr Ser Phe His Leu Lys
85 90 95
Lys Pro Ser Ala Leu Val Ser Asp Ser Ala Leu Tyr Phe Cys Ala Val
100 105 110
Arg Asp Asn Ser Gly Gly Ser Asn Tyr Lys Leu Thr Phe Gly Lys Gly
115 120 125
Thr Leu Leu Thr Val Asn Pro Asn Ile Gln Asn Pro Glu Pro Ala Val
130 135 140
Tyr Gln Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe
145 150 155 160
Thr Asp Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly
165 170 175
Thr Phe Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser
180 185 190
Lys Ser Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys
195 200 205
Gln Asp Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val
210 215 220
Pro Cys Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn
225 230 235 240
Leu Asn Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu
245 250 255
Lys Val Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser
260 265 270
Arg Ala Lys Arg Ser Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys
275 280 285
Gln Ala Gly Asp Val Glu Glu Asn Pro Gly Pro Met His Thr Arg Leu
290 295 300
Leu Cys Trp Ala Ala Leu Cys Leu Leu Gly Ala Glu Leu Thr Glu Ala
305 310 315 320
Gly Val Ala Gln Ser Pro Arg Tyr Lys Ile Ile Glu Lys Arg Gln Ser
325 330 335
Val Ala Phe Trp Cys Asn Pro Ile Ser Gly His Ala Thr Leu Tyr Trp
340 345 350
Tyr Gln Gln Ile Leu Gly Gln Gly Pro Lys Leu Leu Ile Gln Phe Gln
355 360 365
Asn Asn Gly Val Val Asp Asp Ser Gln Leu Pro Lys Asp Arg Phe Ser
370 375 380
Ala Glu Arg Leu Lys Gly Val Asp Ser Thr Leu Lys Ile Gln Pro Ala
385 390 395 400
Lys Leu Glu Asp Ser Ala Val Tyr Leu Cys Ala Ser Ser Leu Gly Gln
405 410 415
Gly Gln Thr Gln Tyr Phe Gly Pro Gly Thr Arg Leu Leu Val Leu Glu
420 425 430
Asp Leu Arg Asn Val Thr Pro Pro Lys Val Ser Leu Phe Glu Pro Ser
435 440 445
Lys Ala Glu Ile Ala Asn Lys Gln Lys Ala Thr Leu Val Cys Leu Ala
450 455 460
Arg Gly Phe Phe Pro Asp His Val Glu Leu Ser Trp Trp Val Asn Gly
465 470 475 480
Lys Glu Val His Ser Gly Val Cys Thr Asp Pro Gln Ala Tyr Lys Glu
485 490 495
Ser Asn Tyr Ser Tyr Cys Leu Ser Ser Arg Leu Arg Val Ser Ala Thr
500 505 510
Phe Trp His Asn Pro Arg Asn His Phe Arg Cys Gln Val Gln Phe His
515 520 525
Gly Leu Ser Glu Glu Asp Lys Trp Pro Glu Gly Ser Pro Lys Pro Val
530 535 540
Thr Gln Asn Ile Ser Ala Glu Ala Trp Gly Arg Ala Asp Cys Gly Ile
545 550 555 560
Thr Ser Ala Ser Tyr Gln Gln Gly Val Leu Ser Ala Thr Ile Leu Tyr
565 570 575
Glu Ile Leu Leu Gly Lys Ala Thr Leu Tyr Ala Val Leu Val Ser Thr
580 585 590
Leu Val Val Met Ala Met Val Lys Arg Lys Asn Ser
595 600
<210> 581
<211> 601
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 581
Met Ala Leu Leu Leu Val Pro Ala Phe Gln Val Ile Phe Thr Leu Gly
1 5 10 15
Gly Thr Arg Ala Gln Ser Val Thr Gln Leu Asp Ser Gln Val Pro Val
20 25 30
Phe Glu Glu Ala Pro Val Glu Leu Arg Cys Asn Tyr Ser Ser Ser Val
35 40 45
Ser Val Tyr Leu Phe Trp Tyr Val Gln Tyr Pro Asn Gln Gly Leu Gln
50 55 60
Leu Leu Leu Lys Tyr Leu Ser Gly Ser Thr Leu Val Glu Ser Ile Asn
65 70 75 80
Gly Phe Glu Ala Glu Phe Asn Lys Ser Gln Thr Ser Phe His Leu Arg
85 90 95
Lys Pro Ser Val His Ile Ser Asp Thr Ala Glu Tyr Phe Cys Ala Val
100 105 110
Arg Gly Ser Ser Gly Thr Tyr Lys Tyr Ile Phe Gly Thr Gly Thr Arg
115 120 125
Leu Lys Val Leu Ala Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr Gln
130 135 140
Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr Asp
145 150 155 160
Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr Phe
165 170 175
Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys Ser
180 185 190
Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln Asp
195 200 205
Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro Cys
210 215 220
Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu Asn
225 230 235 240
Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys Val
245 250 255
Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser Arg Ala
260 265 270
Lys Arg Ser Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln Ala
275 280 285
Gly Asp Val Glu Glu Asn Pro Gly Pro Met His Ile Arg Leu Leu Cys
290 295 300
Arg Val Ala Phe Cys Phe Leu Ala Val Gly Leu Val Asp Val Lys Val
305 310 315 320
Thr Gln Ser Ser Arg Tyr Leu Val Lys Arg Thr Gly Glu Lys Val Phe
325 330 335
Leu Glu Cys Val Gln Asp Met Asp His Glu Asn Met Phe Trp Tyr Arg
340 345 350
Gln Asp Pro Gly Leu Gly Leu Arg Leu Ile Tyr Phe Ser Tyr Asp Val
355 360 365
Lys Met Lys Glu Lys Gly Asp Ile Pro Glu Gly Tyr Ser Val Ser Arg
370 375 380
Glu Lys Lys Glu Arg Phe Ser Leu Ile Leu Glu Ser Ala Ser Thr Asn
385 390 395 400
Gln Thr Ser Met Tyr Leu Cys Ala Ser Lys Gly Asp Gln Asn Thr Glu
405 410 415
Ala Phe Phe Gly Gln Gly Thr Arg Leu Thr Val Val Glu Asp Leu Arg
420 425 430
Asn Val Thr Pro Pro Lys Val Ser Leu Phe Glu Pro Ser Lys Ala Glu
435 440 445
Ile Ala Asn Lys Gln Lys Ala Thr Leu Val Cys Leu Ala Arg Gly Phe
450 455 460
Phe Pro Asp His Val Glu Leu Ser Trp Trp Val Asn Gly Lys Glu Val
465 470 475 480
His Ser Gly Val Cys Thr Asp Pro Gln Ala Tyr Lys Glu Ser Asn Tyr
485 490 495
Ser Tyr Cys Leu Ser Ser Arg Leu Arg Val Ser Ala Thr Phe Trp His
500 505 510
Asn Pro Arg Asn His Phe Arg Cys Gln Val Gln Phe His Gly Leu Ser
515 520 525
Glu Glu Asp Lys Trp Pro Glu Gly Ser Pro Lys Pro Val Thr Gln Asn
530 535 540
Ile Ser Ala Glu Ala Trp Gly Arg Ala Asp Cys Gly Ile Thr Ser Ala
545 550 555 560
Ser Tyr Gln Gln Gly Val Leu Ser Ala Thr Ile Leu Tyr Glu Ile Leu
565 570 575
Leu Gly Lys Ala Thr Leu Tyr Ala Val Leu Val Ser Thr Leu Val Val
580 585 590
Met Ala Met Val Lys Arg Lys Asn Ser
595 600
<210> 582
<211> 598
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 582
Met Ala Gly Val Phe Leu Leu Tyr Val Ser Met Lys Met Gly Gly Thr
1 5 10 15
Thr Gly Gln Asn Ile Asp Gln Pro Thr Glu Met Thr Ala Thr Glu Gly
20 25 30
Ala Ile Val Gln Ile Asn Cys Thr Tyr Gln Thr Ser Gly Phe Asn Gly
35 40 45
Leu Phe Trp Tyr Gln Gln His Ala Gly Glu Ala Pro Thr Phe Leu Ser
50 55 60
Tyr Asn Val Leu Asp Gly Leu Glu Glu Lys Gly Arg Phe Ser Ser Phe
65 70 75 80
Leu Ser Arg Ser Lys Gly Tyr Ser Tyr Leu Leu Leu Lys Glu Leu Gln
85 90 95
Met Lys Asp Ser Ala Ser Tyr Leu Cys Ala Val Arg Asp Leu Gln Thr
100 105 110
Gly Ala Asn Asn Leu Phe Phe Gly Thr Gly Thr Arg Leu Thr Val Ile
115 120 125
Pro Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr Gln Leu Lys Asp Pro
130 135 140
Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr Asp Phe Asp Ser Gln
145 150 155 160
Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr Phe Ile Thr Asp Lys
165 170 175
Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys Ser Asn Gly Ala Ile
180 185 190
Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln Asp Ile Phe Lys Glu
195 200 205
Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro Cys Asp Ala Thr Leu
210 215 220
Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu Asn Phe Gln Asn Leu
225 230 235 240
Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys Val Ala Gly Phe Asn
245 250 255
Leu Leu Met Thr Leu Arg Leu Trp Ser Ser Arg Ala Lys Arg Ser Gly
260 265 270
Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln Ala Gly Asp Val Glu
275 280 285
Glu Asn Pro Gly Pro Met His Ile Arg Leu Leu Cys Arg Val Ala Phe
290 295 300
Cys Phe Leu Ala Val Gly Leu Val Asp Val Lys Val Thr Gln Ser Ser
305 310 315 320
Arg Tyr Leu Val Lys Arg Thr Gly Glu Lys Val Phe Leu Glu Cys Val
325 330 335
Gln Asp Met Asp His Glu Asn Met Phe Trp Tyr Arg Gln Asp Pro Gly
340 345 350
Leu Gly Leu Arg Leu Ile Tyr Phe Ser Tyr Asp Val Lys Met Lys Glu
355 360 365
Lys Gly Asp Ile Pro Glu Gly Tyr Ser Val Ser Arg Glu Lys Lys Glu
370 375 380
Arg Phe Ser Leu Ile Leu Glu Ser Ala Ser Thr Asn Gln Thr Ser Met
385 390 395 400
Tyr Leu Cys Ala Ser Ser Leu Thr Phe Gly Thr Thr Glu Ala Phe Phe
405 410 415
Gly Gln Gly Thr Arg Leu Thr Val Val Glu Asp Leu Arg Asn Val Thr
420 425 430
Pro Pro Lys Val Ser Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn
435 440 445
Lys Gln Lys Ala Thr Leu Val Cys Leu Ala Arg Gly Phe Phe Pro Asp
450 455 460
His Val Glu Leu Ser Trp Trp Val Asn Gly Lys Glu Val His Ser Gly
465 470 475 480
Val Cys Thr Asp Pro Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys
485 490 495
Leu Ser Ser Arg Leu Arg Val Ser Ala Thr Phe Trp His Asn Pro Arg
500 505 510
Asn His Phe Arg Cys Gln Val Gln Phe His Gly Leu Ser Glu Glu Asp
515 520 525
Lys Trp Pro Glu Gly Ser Pro Lys Pro Val Thr Gln Asn Ile Ser Ala
530 535 540
Glu Ala Trp Gly Arg Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln
545 550 555 560
Gln Gly Val Leu Ser Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys
565 570 575
Ala Thr Leu Tyr Ala Val Leu Val Ser Thr Leu Val Val Met Ala Met
580 585 590
Val Lys Arg Lys Asn Ser
595
<210> 583
<211> 599
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 583
Met Ala Leu Leu Leu Val Pro Ala Phe Gln Val Ile Phe Thr Leu Gly
1 5 10 15
Gly Thr Arg Ala Gln Ser Val Thr Gln Leu Asp Ser Gln Val Pro Val
20 25 30
Phe Glu Glu Ala Pro Val Glu Leu Arg Cys Asn Tyr Ser Ser Ser Val
35 40 45
Ser Val Tyr Leu Phe Trp Tyr Val Gln Tyr Pro Asn Gln Gly Leu Gln
50 55 60
Leu Leu Leu Lys Tyr Leu Ser Gly Ser Thr Leu Val Glu Ser Ile Asn
65 70 75 80
Gly Phe Glu Ala Glu Phe Asn Lys Ser Gln Thr Ser Phe His Leu Arg
85 90 95
Lys Pro Ser Val His Ile Ser Asp Thr Ala Glu Tyr Phe Cys Ala Val
100 105 110
Ser Asp Leu Val Arg Asp Asp Lys Ile Ile Phe Gly Lys Gly Thr Arg
115 120 125
Leu His Ile Leu Pro Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr Gln
130 135 140
Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr Asp
145 150 155 160
Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr Phe
165 170 175
Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys Ser
180 185 190
Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln Asp
195 200 205
Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro Cys
210 215 220
Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu Asn
225 230 235 240
Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys Val
245 250 255
Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser Arg Ala
260 265 270
Lys Arg Ser Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln Ala
275 280 285
Gly Asp Val Glu Glu Asn Pro Gly Pro Met His Ile Gly Leu Leu Cys
290 295 300
Cys Val Ala Phe Ser Leu Leu Trp Ala Ser Pro Val Asn Ala Gly Val
305 310 315 320
Thr Gln Thr Pro Lys Phe Gln Val Leu Lys Thr Gly Gln Ser Met Thr
325 330 335
Leu Gln Cys Ala Gln Asp Met Asn His Asn Ser Met Tyr Trp Tyr Arg
340 345 350
Gln Asp Pro Gly Met Gly Leu Arg Leu Ile Tyr Tyr Ser Ala Ser Glu
355 360 365
Gly Thr Thr Asp Lys Gly Glu Val Pro Asn Gly Tyr Asn Val Ser Arg
370 375 380
Leu Asn Lys Arg Glu Phe Ser Leu Arg Leu Glu Ser Ala Ala Pro Ser
385 390 395 400
Gln Thr Ser Val Tyr Phe Cys Ala Ser Ile Gly Gly Phe Glu Ala Phe
405 410 415
Phe Gly Gln Gly Thr Arg Leu Thr Val Val Glu Asp Leu Arg Asn Val
420 425 430
Thr Pro Pro Lys Val Ser Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala
435 440 445
Asn Lys Gln Lys Ala Thr Leu Val Cys Leu Ala Arg Gly Phe Phe Pro
450 455 460
Asp His Val Glu Leu Ser Trp Trp Val Asn Gly Lys Glu Val His Ser
465 470 475 480
Gly Val Cys Thr Asp Pro Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr
485 490 495
Cys Leu Ser Ser Arg Leu Arg Val Ser Ala Thr Phe Trp His Asn Pro
500 505 510
Arg Asn His Phe Arg Cys Gln Val Gln Phe His Gly Leu Ser Glu Glu
515 520 525
Asp Lys Trp Pro Glu Gly Ser Pro Lys Pro Val Thr Gln Asn Ile Ser
530 535 540
Ala Glu Ala Trp Gly Arg Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr
545 550 555 560
Gln Gln Gly Val Leu Ser Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly
565 570 575
Lys Ala Thr Leu Tyr Ala Val Leu Val Ser Thr Leu Val Val Met Ala
580 585 590
Met Val Lys Arg Lys Asn Ser
595
<210> 584
<211> 597
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 584
Met Ala Gly Val Phe Leu Leu Tyr Val Ser Met Lys Met Gly Gly Thr
1 5 10 15
Thr Gly Gln Asn Ile Asp Gln Pro Thr Glu Met Thr Ala Thr Glu Gly
20 25 30
Ala Ile Val Gln Ile Asn Cys Thr Tyr Gln Thr Ser Gly Phe Asn Gly
35 40 45
Leu Phe Trp Tyr Gln Gln His Ala Gly Glu Ala Pro Thr Phe Leu Ser
50 55 60
Tyr Asn Val Leu Asp Gly Leu Glu Glu Lys Gly Arg Phe Ser Ser Phe
65 70 75 80
Leu Ser Arg Ser Lys Gly Tyr Ser Tyr Leu Leu Leu Lys Glu Leu Gln
85 90 95
Met Lys Asp Ser Ala Ser Tyr Leu Cys Ala Val Tyr Thr Gly Gly Phe
100 105 110
Lys Thr Ile Phe Gly Ala Gly Thr Arg Leu Phe Val Lys Ala Asn Ile
115 120 125
Gln Asn Pro Glu Pro Ala Val Tyr Gln Leu Lys Asp Pro Arg Ser Gln
130 135 140
Asp Ser Thr Leu Cys Leu Phe Thr Asp Phe Asp Ser Gln Ile Asn Val
145 150 155 160
Pro Lys Thr Met Glu Ser Gly Thr Phe Ile Thr Asp Lys Cys Val Leu
165 170 175
Asp Met Lys Ala Met Asp Ser Lys Ser Asn Gly Ala Ile Ala Trp Ser
180 185 190
Asn Gln Thr Ser Phe Thr Cys Gln Asp Ile Phe Lys Glu Thr Asn Ala
195 200 205
Thr Tyr Pro Ser Ser Asp Val Pro Cys Asp Ala Thr Leu Thr Glu Lys
210 215 220
Ser Phe Glu Thr Asp Met Asn Leu Asn Phe Gln Asn Leu Leu Val Ile
225 230 235 240
Val Leu Arg Ile Leu Leu Leu Lys Val Ala Gly Phe Asn Leu Leu Met
245 250 255
Thr Leu Arg Leu Trp Ser Ser Arg Ala Lys Arg Ser Gly Ser Gly Ala
260 265 270
Thr Asn Phe Ser Leu Leu Lys Gln Ala Gly Asp Val Glu Glu Asn Pro
275 280 285
Gly Pro Met His Thr Arg Leu Leu Cys Trp Ala Ala Leu Cys Leu Leu
290 295 300
Gly Ala Glu Leu Thr Glu Ala Gly Val Ala Gln Ser Pro Arg Tyr Lys
305 310 315 320
Ile Ile Glu Lys Arg Gln Ser Val Ala Phe Trp Cys Asn Pro Ile Ser
325 330 335
Gly His Ala Thr Leu Tyr Trp Tyr Gln Gln Ile Leu Gly Gln Gly Pro
340 345 350
Lys Leu Leu Ile Gln Phe Gln Asn Asn Gly Val Val Asp Asp Ser Gln
355 360 365
Leu Pro Lys Asp Arg Phe Ser Ala Glu Arg Leu Lys Gly Val Asp Ser
370 375 380
Thr Leu Lys Ile Gln Pro Ala Lys Leu Glu Asp Ser Ala Val Tyr Leu
385 390 395 400
Cys Ala Ser Asn Leu Gly Gly Gly Ser Thr Asp Thr Gln Tyr Phe Gly
405 410 415
Pro Gly Thr Arg Leu Thr Val Leu Glu Asp Leu Arg Asn Val Thr Pro
420 425 430
Pro Lys Val Ser Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys
435 440 445
Gln Lys Ala Thr Leu Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His
450 455 460
Val Glu Leu Ser Trp Trp Val Asn Gly Lys Glu Val His Ser Gly Val
465 470 475 480
Cys Thr Asp Pro Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu
485 490 495
Ser Ser Arg Leu Arg Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn
500 505 510
His Phe Arg Cys Gln Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys
515 520 525
Trp Pro Glu Gly Ser Pro Lys Pro Val Thr Gln Asn Ile Ser Ala Glu
530 535 540
Ala Trp Gly Arg Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln
545 550 555 560
Gly Val Leu Ser Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala
565 570 575
Thr Leu Tyr Ala Val Leu Val Ser Thr Leu Val Val Met Ala Met Val
580 585 590
Lys Arg Lys Asn Ser
595
<210> 585
<211> 599
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 585
Met Ala Gly Val Phe Leu Leu Tyr Val Ser Met Lys Met Gly Gly Thr
1 5 10 15
Thr Gly Gln Asn Ile Asp Gln Pro Thr Glu Met Thr Ala Thr Glu Gly
20 25 30
Ala Ile Val Gln Ile Asn Cys Thr Tyr Gln Thr Ser Gly Phe Asn Gly
35 40 45
Leu Phe Trp Tyr Gln Gln His Ala Gly Glu Ala Pro Thr Phe Leu Ser
50 55 60
Tyr Asn Val Leu Asp Gly Leu Glu Glu Lys Gly Arg Phe Ser Ser Phe
65 70 75 80
Leu Ser Arg Ser Lys Gly Tyr Ser Tyr Leu Leu Leu Lys Glu Leu Gln
85 90 95
Met Lys Asp Ser Ala Ser Tyr Leu Cys Ala Phe Tyr Tyr Gly Gly Ser
100 105 110
Gln Gly Asn Leu Ile Phe Gly Lys Gly Thr Lys Leu Ser Val Lys Pro
115 120 125
Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr Gln Leu Lys Asp Pro Arg
130 135 140
Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr Asp Phe Asp Ser Gln Ile
145 150 155 160
Asn Val Pro Lys Thr Met Glu Ser Gly Thr Phe Ile Thr Asp Lys Cys
165 170 175
Val Leu Asp Met Lys Ala Met Asp Ser Lys Ser Asn Gly Ala Ile Ala
180 185 190
Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln Asp Ile Phe Lys Glu Thr
195 200 205
Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro Cys Asp Ala Thr Leu Thr
210 215 220
Glu Lys Ser Phe Glu Thr Asp Met Asn Leu Asn Phe Gln Asn Leu Leu
225 230 235 240
Val Ile Val Leu Arg Ile Leu Leu Leu Lys Val Ala Gly Phe Asn Leu
245 250 255
Leu Met Thr Leu Arg Leu Trp Ser Ser Arg Ala Lys Arg Ser Gly Ser
260 265 270
Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln Ala Gly Asp Val Glu Glu
275 280 285
Asn Pro Gly Pro Met His Thr Arg Leu Leu Cys Trp Val Val Leu Gly
290 295 300
Phe Leu Gly Thr Asp His Thr Gly Ala Gly Val Ser Gln Ser Pro Arg
305 310 315 320
Tyr Lys Val Ala Lys Arg Gly Gln Asp Val Ala Leu Arg Cys Asp Pro
325 330 335
Ile Ser Gly His Val Ser Leu Phe Trp Tyr Gln Gln Ala Leu Gly Gln
340 345 350
Gly Pro Glu Phe Leu Thr Tyr Phe Gln Asn Glu Ala Gln Leu Asp Lys
355 360 365
Ser Gly Leu Pro Ser Asp Arg Phe Phe Ala Glu Arg Pro Glu Gly Ser
370 375 380
Val Ser Thr Leu Lys Ile Gln Arg Thr Gln Gln Glu Asp Ser Ala Val
385 390 395 400
Tyr Leu Cys Ala Ser Ser Phe Gly Ser Gly Ser Thr Asp Thr Gln Tyr
405 410 415
Phe Gly Pro Gly Thr Arg Leu Thr Val Leu Glu Asp Leu Arg Asn Val
420 425 430
Thr Pro Pro Lys Val Ser Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala
435 440 445
Asn Lys Gln Lys Ala Thr Leu Val Cys Leu Ala Arg Gly Phe Phe Pro
450 455 460
Asp His Val Glu Leu Ser Trp Trp Val Asn Gly Lys Glu Val His Ser
465 470 475 480
Gly Val Cys Thr Asp Pro Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr
485 490 495
Cys Leu Ser Ser Arg Leu Arg Val Ser Ala Thr Phe Trp His Asn Pro
500 505 510
Arg Asn His Phe Arg Cys Gln Val Gln Phe His Gly Leu Ser Glu Glu
515 520 525
Asp Lys Trp Pro Glu Gly Ser Pro Lys Pro Val Thr Gln Asn Ile Ser
530 535 540
Ala Glu Ala Trp Gly Arg Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr
545 550 555 560
Gln Gln Gly Val Leu Ser Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly
565 570 575
Lys Ala Thr Leu Tyr Ala Val Leu Val Ser Thr Leu Val Val Met Ala
580 585 590
Met Val Lys Arg Lys Asn Ser
595
<210> 586
<211> 599
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 586
Met Ala Gly Val Phe Leu Leu Tyr Val Ser Met Lys Met Gly Gly Thr
1 5 10 15
Thr Gly Gln Asn Ile Asp Gln Pro Thr Glu Met Thr Ala Thr Glu Gly
20 25 30
Ala Ile Val Gln Ile Asn Cys Thr Tyr Gln Thr Ser Gly Phe Asn Gly
35 40 45
Leu Phe Trp Tyr Gln Gln His Ala Gly Glu Ala Pro Thr Phe Leu Ser
50 55 60
Tyr Asn Val Leu Asp Gly Leu Glu Glu Lys Gly Arg Phe Ser Ser Phe
65 70 75 80
Leu Ser Arg Ser Lys Gly Tyr Ser Tyr Leu Leu Leu Lys Glu Leu Gln
85 90 95
Met Lys Asp Ser Ala Ser Tyr Leu Cys Ala Val Tyr Pro Gly Gly Ser
100 105 110
Gln Gly Asn Leu Ile Phe Gly Lys Gly Thr Lys Leu Ser Val Lys Pro
115 120 125
Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr Gln Leu Lys Asp Pro Arg
130 135 140
Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr Asp Phe Asp Ser Gln Ile
145 150 155 160
Asn Val Pro Lys Thr Met Glu Ser Gly Thr Phe Ile Thr Asp Lys Cys
165 170 175
Val Leu Asp Met Lys Ala Met Asp Ser Lys Ser Asn Gly Ala Ile Ala
180 185 190
Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln Asp Ile Phe Lys Glu Thr
195 200 205
Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro Cys Asp Ala Thr Leu Thr
210 215 220
Glu Lys Ser Phe Glu Thr Asp Met Asn Leu Asn Phe Gln Asn Leu Leu
225 230 235 240
Val Ile Val Leu Arg Ile Leu Leu Leu Lys Val Ala Gly Phe Asn Leu
245 250 255
Leu Met Thr Leu Arg Leu Trp Ser Ser Arg Ala Lys Arg Ser Gly Ser
260 265 270
Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln Ala Gly Asp Val Glu Glu
275 280 285
Asn Pro Gly Pro Met His Thr Arg Leu Leu Cys Trp Ala Ala Leu Cys
290 295 300
Leu Leu Gly Ala Glu Leu Thr Glu Ala Gly Val Ala Gln Ser Pro Arg
305 310 315 320
Tyr Lys Ile Ile Glu Lys Arg Gln Ser Val Ala Phe Trp Cys Asn Pro
325 330 335
Ile Ser Gly His Ala Thr Leu Tyr Trp Tyr Gln Gln Ile Leu Gly Gln
340 345 350
Gly Pro Lys Leu Leu Ile Gln Phe Gln Asn Asn Gly Val Val Asp Asp
355 360 365
Ser Gln Leu Pro Lys Asp Arg Phe Ser Ala Glu Arg Leu Lys Gly Val
370 375 380
Asp Ser Thr Leu Lys Ile Gln Pro Ala Lys Leu Glu Asp Ser Ala Val
385 390 395 400
Tyr Leu Cys Ala Ser Ser Leu Gly Thr Gly Ser Thr Asp Thr Gln Tyr
405 410 415
Phe Gly Pro Gly Thr Arg Leu Thr Val Leu Glu Asp Leu Arg Asn Val
420 425 430
Thr Pro Pro Lys Val Ser Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala
435 440 445
Asn Lys Gln Lys Ala Thr Leu Val Cys Leu Ala Arg Gly Phe Phe Pro
450 455 460
Asp His Val Glu Leu Ser Trp Trp Val Asn Gly Lys Glu Val His Ser
465 470 475 480
Gly Val Cys Thr Asp Pro Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr
485 490 495
Cys Leu Ser Ser Arg Leu Arg Val Ser Ala Thr Phe Trp His Asn Pro
500 505 510
Arg Asn His Phe Arg Cys Gln Val Gln Phe His Gly Leu Ser Glu Glu
515 520 525
Asp Lys Trp Pro Glu Gly Ser Pro Lys Pro Val Thr Gln Asn Ile Ser
530 535 540
Ala Glu Ala Trp Gly Arg Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr
545 550 555 560
Gln Gln Gly Val Leu Ser Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly
565 570 575
Lys Ala Thr Leu Tyr Ala Val Leu Val Ser Thr Leu Val Val Met Ala
580 585 590
Met Val Lys Arg Lys Asn Ser
595
<210> 587
<211> 606
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 587
Met Ala Ser Ile Arg Ala Val Phe Ile Phe Leu Trp Leu Gln Leu Asp
1 5 10 15
Leu Val Asn Gly Glu Asn Val Glu Gln His Pro Ser Thr Leu Ser Val
20 25 30
Gln Glu Gly Asp Ser Ala Val Ile Lys Cys Thr Tyr Ser Asp Ser Ala
35 40 45
Ser Asn Tyr Phe Pro Trp Tyr Lys Gln Glu Leu Gly Lys Gly Pro Gln
50 55 60
Leu Ile Ile Asp Ile Arg Ser Asn Val Gly Glu Lys Lys Asp Gln Arg
65 70 75 80
Ile Ala Val Thr Leu Asn Lys Thr Ala Lys His Phe Ser Leu His Ile
85 90 95
Thr Glu Thr Gln Pro Glu Asp Ser Ala Val Tyr Phe Cys Ala Ala Ser
100 105 110
Lys Ser Ala Ile Met Val Val Leu Gln Thr Ser Ser Ser Leu Glu Leu
115 120 125
Ala Leu Cys Leu Leu Ser Ser Gln Val Asn Ile Gln Asn Pro Glu Pro
130 135 140
Ala Val Tyr Gln Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys
145 150 155 160
Leu Phe Thr Asp Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu
165 170 175
Ser Gly Thr Phe Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met
180 185 190
Asp Ser Lys Ser Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe
195 200 205
Thr Cys Gln Asp Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser
210 215 220
Asp Val Pro Cys Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp
225 230 235 240
Met Asn Leu Asn Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu
245 250 255
Leu Leu Lys Val Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp
260 265 270
Ser Ser Arg Ala Lys Arg Ser Gly Ser Gly Ala Thr Asn Phe Ser Leu
275 280 285
Leu Lys Gln Ala Gly Asp Val Glu Glu Asn Pro Gly Pro Met His Pro
290 295 300
Gln Leu Leu Gly Tyr Val Val Leu Cys Leu Leu Gly Ala Gly Pro Leu
305 310 315 320
Glu Ala Gln Val Thr Gln Asn Pro Arg Tyr Leu Ile Thr Val Thr Gly
325 330 335
Lys Lys Leu Thr Val Thr Cys Ser Gln Asn Met Asn His Glu Tyr Met
340 345 350
Ser Trp Tyr Arg Gln Asp Pro Gly Leu Gly Leu Arg Gln Ile Tyr Tyr
355 360 365
Ser Met Asn Val Glu Val Thr Asp Lys Gly Asp Val Pro Glu Gly Tyr
370 375 380
Lys Val Ser Arg Lys Glu Lys Arg Asn Phe Pro Leu Ile Leu Glu Ser
385 390 395 400
Pro Ser Pro Asn Gln Thr Ser Leu Tyr Phe Cys Ala Ser Ser Ile Gln
405 410 415
Gln Gly Ala Asp Thr Gln Tyr Phe Gly Pro Gly Thr Arg Leu Thr Val
420 425 430
Leu Glu Asp Leu Arg Asn Val Thr Pro Pro Lys Val Ser Leu Phe Glu
435 440 445
Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln Lys Ala Thr Leu Val Cys
450 455 460
Leu Ala Arg Gly Phe Phe Pro Asp His Val Glu Leu Ser Trp Trp Val
465 470 475 480
Asn Gly Lys Glu Val His Ser Gly Val Cys Thr Asp Pro Gln Ala Tyr
485 490 495
Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser Arg Leu Arg Val Ser
500 505 510
Ala Thr Phe Trp His Asn Pro Arg Asn His Phe Arg Cys Gln Val Gln
515 520 525
Phe His Gly Leu Ser Glu Glu Asp Lys Trp Pro Glu Gly Ser Pro Lys
530 535 540
Pro Val Thr Gln Asn Ile Ser Ala Glu Ala Trp Gly Arg Ala Asp Cys
545 550 555 560
Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly Val Leu Ser Ala Thr Ile
565 570 575
Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu Tyr Ala Val Leu Val
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Ser Thr Leu Val Val Met Ala Met Val Lys Arg Lys Asn Ser
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<210> 588
<211> 603
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 588
Met Ala Ser Leu Arg Val Leu Leu Val Ile Leu Trp Leu Gln Leu Ser
1 5 10 15
Trp Val Trp Ser Gln Gln Lys Glu Val Glu Gln Asn Ser Gly Pro Leu
20 25 30
Ser Val Pro Glu Gly Ala Ile Ala Ser Leu Asn Cys Thr Tyr Ser Asp
35 40 45
Arg Gly Ser Gln Ser Phe Phe Trp Tyr Arg Gln Tyr Ser Gly Lys Ser
50 55 60
Pro Glu Leu Ile Met Phe Ile Tyr Ser Asn Gly Asp Lys Glu Asp Gly
65 70 75 80
Arg Phe Thr Ala Gln Leu Asn Lys Ala Ser Gln Tyr Val Ser Leu Leu
85 90 95
Ile Arg Asp Ser Gln Pro Ser Asp Ser Ala Thr Tyr Leu Cys Ala Trp
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Asn Ser Gly Gly Ser Asn Tyr Lys Leu Thr Phe Gly Lys Gly Thr Leu
115 120 125
Leu Thr Val Asn Pro Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr Gln
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Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr Asp
145 150 155 160
Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr Phe
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Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys Ser
180 185 190
Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln Asp
195 200 205
Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro Cys
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Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu Asn
225 230 235 240
Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys Val
245 250 255
Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser Arg Ala
260 265 270
Lys Arg Ser Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln Ala
275 280 285
Gly Asp Val Glu Glu Asn Pro Gly Pro Met His Leu Gly Leu Leu Cys
290 295 300
Cys Gly Ala Phe Ser Leu Leu Trp Ala Gly Pro Val Asn Ala Gly Val
305 310 315 320
Thr Gln Thr Pro Lys Phe Arg Val Leu Lys Thr Gly Gln Ser Met Thr
325 330 335
Leu Leu Cys Ala Gln Asp Met Asn His Glu Tyr Met Tyr Trp Tyr Arg
340 345 350
Gln Asp Pro Gly Met Gly Leu Arg Leu Ile His Tyr Ser Val Gly Glu
355 360 365
Gly Thr Thr Ala Lys Gly Glu Val Pro Asp Gly Tyr Asn Val Ser Arg
370 375 380
Leu Lys Lys Gln Asn Phe Leu Leu Gly Leu Glu Ser Ala Ala Pro Ser
385 390 395 400
Gln Thr Ser Val Tyr Phe Cys Ala Ser Ser Tyr Ser Gln Ala Trp Gly
405 410 415
Gln Pro Gln His Phe Gly Asp Gly Thr Arg Leu Ser Ile Leu Glu Asp
420 425 430
Leu Arg Asn Val Thr Pro Pro Lys Val Ser Leu Phe Glu Pro Ser Lys
435 440 445
Ala Glu Ile Ala Asn Lys Gln Lys Ala Thr Leu Val Cys Leu Ala Arg
450 455 460
Gly Phe Phe Pro Asp His Val Glu Leu Ser Trp Trp Val Asn Gly Lys
465 470 475 480
Glu Val His Ser Gly Val Cys Thr Asp Pro Gln Ala Tyr Lys Glu Ser
485 490 495
Asn Tyr Ser Tyr Cys Leu Ser Ser Arg Leu Arg Val Ser Ala Thr Phe
500 505 510
Trp His Asn Pro Arg Asn His Phe Arg Cys Gln Val Gln Phe His Gly
515 520 525
Leu Ser Glu Glu Asp Lys Trp Pro Glu Gly Ser Pro Lys Pro Val Thr
530 535 540
Gln Asn Ile Ser Ala Glu Ala Trp Gly Arg Ala Asp Cys Gly Ile Thr
545 550 555 560
Ser Ala Ser Tyr Gln Gln Gly Val Leu Ser Ala Thr Ile Leu Tyr Glu
565 570 575
Ile Leu Leu Gly Lys Ala Thr Leu Tyr Ala Val Leu Val Ser Thr Leu
580 585 590
Val Val Met Ala Met Val Lys Arg Lys Asn Ser
595 600
<210> 589
<211> 603
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成
<400> 589
Met Ala Lys Asn Pro Leu Ala Ala Pro Leu Leu Ile Leu Trp Phe His
1 5 10 15
Leu Asp Cys Val Ser Ser Ile Leu Asn Val Glu Gln Ser Pro Gln Ser
20 25 30
Leu His Val Gln Glu Gly Asp Ser Thr Asn Phe Thr Cys Ser Phe Pro
35 40 45
Ser Ser Asn Phe Tyr Ala Leu His Trp Tyr Arg Trp Glu Thr Ala Lys
50 55 60
Ser Pro Glu Ala Leu Phe Val Met Thr Leu Asn Gly Asp Glu Lys Lys
65 70 75 80
Lys Gly Arg Ile Ser Ala Thr Leu Asn Thr Lys Glu Gly Tyr Ser Tyr
85 90 95
Leu Tyr Ile Lys Gly Ser Gln Pro Glu Asp Ser Ala Thr Tyr Leu Cys
100 105 110
Ala Leu Ile Thr Gly Gly Gly Asn Lys Leu Thr Phe Gly Thr Gly Thr
115 120 125
Gln Leu Lys Val Glu Leu Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr
130 135 140
Gln Leu Lys Asp Pro Arg Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr
145 150 155 160
Asp Phe Asp Ser Gln Ile Asn Val Pro Lys Thr Met Glu Ser Gly Thr
165 170 175
Phe Ile Thr Asp Lys Cys Val Leu Asp Met Lys Ala Met Asp Ser Lys
180 185 190
Ser Asn Gly Ala Ile Ala Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln
195 200 205
Asp Ile Phe Lys Glu Thr Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro
210 215 220
Cys Asp Ala Thr Leu Thr Glu Lys Ser Phe Glu Thr Asp Met Asn Leu
225 230 235 240
Asn Phe Gln Asn Leu Leu Val Ile Val Leu Arg Ile Leu Leu Leu Lys
245 250 255
Val Ala Gly Phe Asn Leu Leu Met Thr Leu Arg Leu Trp Ser Ser Arg
260 265 270
Ala Lys Arg Ser Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln
275 280 285
Ala Gly Asp Val Glu Glu Asn Pro Gly Pro Met His Leu Gly Leu Leu
290 295 300
Cys Cys Gly Ala Phe Ser Leu Leu Trp Ala Gly Pro Val Asn Ala Gly
305 310 315 320
Val Thr Gln Thr Pro Lys Phe Arg Val Leu Lys Thr Gly Gln Ser Met
325 330 335
Thr Leu Leu Cys Ala Gln Asp Met Asn His Glu Tyr Met Tyr Trp Tyr
340 345 350
Arg Gln Asp Pro Gly Met Gly Leu Arg Leu Ile His Tyr Ser Val Gly
355 360 365
Glu Gly Thr Thr Ala Lys Gly Glu Val Pro Asp Gly Tyr Asn Val Ser
370 375 380
Arg Leu Lys Lys Gln Asn Phe Leu Leu Gly Leu Glu Ser Ala Ala Pro
385 390 395 400
Ser Gln Thr Ser Val Tyr Phe Cys Ala Ser Arg Leu Gln Gly Trp Asn
405 410 415
Ser Pro Leu His Phe Gly Asn Gly Thr Arg Leu Thr Val Thr Glu Asp
420 425 430
Leu Arg Asn Val Thr Pro Pro Lys Val Ser Leu Phe Glu Pro Ser Lys
435 440 445
Ala Glu Ile Ala Asn Lys Gln Lys Ala Thr Leu Val Cys Leu Ala Arg
450 455 460
Gly Phe Phe Pro Asp His Val Glu Leu Ser Trp Trp Val Asn Gly Lys
465 470 475 480
Glu Val His Ser Gly Val Cys Thr Asp Pro Gln Ala Tyr Lys Glu Ser
485 490 495
Asn Tyr Ser Tyr Cys Leu Ser Ser Arg Leu Arg Val Ser Ala Thr Phe
500 505 510
Trp His Asn Pro Arg Asn His Phe Arg Cys Gln Val Gln Phe His Gly
515 520 525
Leu Ser Glu Glu Asp Lys Trp Pro Glu Gly Ser Pro Lys Pro Val Thr
530 535 540
Gln Asn Ile Ser Ala Glu Ala Trp Gly Arg Ala Asp Cys Gly Ile Thr
545 550 555 560
Ser Ala Ser Tyr Gln Gln Gly Val Leu Ser Ala Thr Ile Leu Tyr Glu
565 570 575
Ile Leu Leu Gly Lys Ala Thr Leu Tyr Ala Val Leu Val Ser Thr Leu
580 585 590
Val Val Met Ala Met Val Lys Arg Lys Asn Ser
595 600
<210> 590
<211> 10
<212> PRT
<213> 智人(Homo sapiens)
<400> 590
Ser Ser Cys Met Gly Gly Met Asn Arg Arg
1 5 10
<210> 591
<211> 10
<212> PRT
<213> 智人(Homo sapiens)
<400> 591
Ser Ser Cys Met Gly Gly Met Asn Trp Arg
1 5 10
<210> 592
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 592
Tyr Met Cys Asn Ser Ser Cys Met Gly Gly Met Asn Trp Arg Pro
1 5 10 15
<210> 593
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 593
Met Cys Asn Ser Ser Cys Met Gly Gly Met Asn Trp Arg Pro Ile
1 5 10 15
<210> 594
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 594
Cys Asn Ser Ser Cys Met Gly Gly Met Asn Trp Arg Pro Ile Leu
1 5 10 15
<210> 595
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 595
Asn Ser Ser Cys Met Gly Gly Met Asn Trp Arg Pro Ile Leu Thr
1 5 10 15
<210> 596
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 596
Ser Ser Cys Met Gly Gly Met Asn Trp Arg Pro Ile Leu Thr Ile
1 5 10 15
<210> 597
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 597
Ser Cys Met Gly Gly Met Asn Trp Arg Pro Ile Leu Thr Ile Ile
1 5 10 15
<210> 598
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 598
Cys Met Gly Gly Met Asn Trp Arg Pro Ile Leu Thr Ile Ile Thr
1 5 10 15
<210> 599
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 599
Met Gly Gly Met Asn Trp Arg Pro Ile Leu Thr Ile Ile Thr Leu
1 5 10 15
<210> 600
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 600
Gly Gly Met Asn Trp Arg Pro Ile Leu Thr Ile Ile Thr Leu Glu
1 5 10 15
<210> 601
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 601
Gly Met Asn Trp Arg Pro Ile Leu Thr Ile Ile Thr Leu Glu Asp
1 5 10 15
<210> 602
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 602
Met Asn Trp Arg Pro Ile Leu Thr Ile Ile Thr Leu Glu Asp Ser
1 5 10 15

Claims (22)

1.分离对由癌症-特异性p53突变编码的突变的p53氨基酸序列具有抗原特异性的T细胞的方法，所述方法包括：
诱导患者的自体抗原呈递细胞(APC)呈递至少一种突变的p53氨基酸序列；
将所述患者的自体T细胞与呈递所述突变的p53氨基酸序列的所述自体APC共培养；和
选择以下自体T细胞，以提供对由所述癌症-特异性p53突变编码的突变的p53氨基酸序列具有抗原特异性的分离的T细胞：其(a)与呈递所述突变的p53氨基酸序列的自体APC共培养和(b)对在由所述患者表达的主要组织相容性复合物(MHC)分子的背景下呈递的所述突变的p53氨基酸序列具有抗原特异性。
2.如权利要求1所述的方法，其中诱导所述患者的自体APC呈递所述突变的p53氨基酸序列包括用包含所述突变的p53氨基酸序列的肽或肽汇集物脉冲APC，所述汇集物中的每种肽包含不同的突变的p53氨基酸序列。
3.如权利要求2所述的方法，其中所述肽或肽汇集物包括SEQ ID NO:2-13的一种或多种突变的p53肽。
4.如权利要求1所述的方法，其中诱导所述患者的自体APC呈递所述突变的p53氨基酸序列包括将编码所述突变的p53氨基酸序列的核苷酸序列引入至所述APC中。
5.如权利要求3所述的方法，其中引入所述自体APC中的所述核苷酸序列是串联微基因(TMG)构建体，每种微基因包含p53基因，每种p53基因包含编码突变的p53氨基酸序列的癌症-特异性p53突变，其中所述TMG构建体中的每种p53基因编码不同的突变的p53氨基酸序列。
6.如权利要求4所述的方法，其中所述TMG构建体编码SEQ ID NO:2-13的一种或多种突变的p53肽。
7.如权利要求4所述的方法，其中所述TMG构建体编码SEQ ID NO:14的氨基酸序列。
8.如权利要求1-6中任一项所述的方法，其中选择对所述突变的p53氨基酸序列具有抗原特异性的自体T细胞包括选择性培养对所述突变的p53氨基酸序列具有抗原特异性的自体T细胞。
9.如权利要求1-7中任一项所述的方法，其中选择对所述突变的p53氨基酸序列具有抗原特异性的自体T细胞包括选择表达程序性细胞死亡1(PD-1)、淋巴细胞-激活基因3(LAG-3)、T细胞免疫球蛋白和粘蛋白结构域3(TIM-3)、4-1BB、OX40和CD107a中的任一种或多种的T细胞。
10.如权利要求1-8中任一项所述的方法，其中选择对所述突变的p53氨基酸序列具有抗原特异性的自体T细胞包括选择以下T细胞：(i)其在与呈递所述突变的p53氨基酸序列的APC共培养后，相比由阴性对照分泌的一种或多种细胞因子的量，分泌更大量的所述一种或多种细胞因子，或(ii)其中在与呈递所述突变的p53氨基酸序列的APC共培养后，相比分泌一种或多种细胞因子的阴性对照T细胞的数量，至少两倍数量的T细胞分泌所述一种或多种细胞因子。
11.如权利要求9所述的方法，其中所述一种或多种细胞因子包括干扰素(IFN)-γ、白介素(IL)-2、肿瘤坏死因子α(TNF-α)、粒细胞/单核细胞集落刺激因子(GM-CSF)、IL-4、IL-5、IL-9、IL-10、IL-17和IL-22。
12.分离对由癌症-特异性p53突变编码的突变的p53氨基酸序列具有抗原特异性的T细胞受体(TCR)或其抗原结合部分的方法，所述方法包括：
根据权利要求1-10中任一项所述的方法，分离对由癌症-特异性p53突变编码的突变的p53氨基酸序列具有抗原特异性的T细胞；和
从选定的自体T细胞分离编码所述TCR或其抗原结合部分的核苷酸序列，其中所述TCR或其抗原结合部分对由所述癌症-特异性p53突变编码的所述突变的p53氨基酸序列具有抗原特异性。
13.制备表达对由癌症-特异性p53突变编码的突变的p53氨基酸序列具有抗原特异性的TCR或其抗原结合部分的细胞群的方法，所述方法包括：
根据权利要求11所述的方法分离TCR或其抗原结合部分，和
将编码分离的TCR或其抗原结合部分的核苷酸序列引入至外周血单核细胞(PBMC)中以获得表达所述TCR或其抗原结合部分的细胞。
14.制备对由癌症-特异性p53突变编码的突变的p53氨基酸序列具有抗原特异性的T细胞群的方法，所述方法包括：
根据权利要求1-10中任一项所述的方法分离T细胞，和
扩大选定的自体T细胞的数量以获得对由所述癌症-特异性p53突变编码的所述突变的p53氨基酸序列具有抗原特异性的T细胞群。
15.如权利要求13所述的方法，其中扩大其细胞的数量包括用饲养PBMC、白介素(IL)-2和OKT3抗体培养所述选定的细胞。
16.分离的细胞群，其根据权利要求12-14中任一项所述的方法制备。
17.药物组合物，其包含权利要求15所述的分离的细胞群和药学上可接受的载体。
18.如权利要求15所述的分离的细胞群或如权利要求16所述的药物组合物，其用于治疗或预防患者中的癌症的用途。
19.根据权利要求17所述用途的分离的细胞群或药物组合物，其中所述癌症是上皮癌。
20.根据权利要求17所述用途的分离的细胞群或药物组合物，其中所述癌症是胆管癌、黑素瘤、结肠癌、直肠癌、卵巢癌、子宫内膜癌、非小细胞肺癌(NSCLC)、成胶质细胞瘤、子宫颈癌、头颈癌、乳房癌、胰腺癌或膀胱癌。
21.根据权利要求17-19中任一项所述用途的分离的细胞群或包含分离的细胞群的药物组合物，其中所述分离的细胞群对于所述患者是自体的。
22.根据权利要求17-19中任一项所述用途的分离的细胞群或包含分离的细胞群的药物组合物，其中所述分离的细胞群对于所述患者是同种异体的。
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