CN110596385A - 用于评估结肠肿瘤的存在或风险的方法 - Google Patents

用于评估结肠肿瘤的存在或风险的方法 Download PDF

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CN110596385A
CN110596385A CN201910577840.7A CN201910577840A CN110596385A CN 110596385 A CN110596385 A CN 110596385A CN 201910577840 A CN201910577840 A CN 201910577840A CN 110596385 A CN110596385 A CN 110596385A
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约翰·布卢姆
瑞恩·本茨
莉萨·克罗纳
罗斯林·狄龙
阿尔洛·兰德尔
杰弗里·琼斯
希瑟·斯科尔
汤姆·斯托克菲希
布鲁斯·威尔考克斯
丹尼尔·鲁德尔曼
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Abstract

公开的方法用于预测或评估患者的结肠肿瘤状态。这些方法可用于确定肿瘤的性质、复发或患者对治疗的反应。该方法的一些实施方案包括生成用于临床管理的报告。本文提供的方法旨在检测技术变化，并允许数据归一化及提高信号检测，以及构建疾病状态和反应的预测性蛋白质谱。

Description

用于评估结肠肿瘤的存在或风险的方法
本申请是申请日为2013年12月02日、申请号为 201380071930.X、发明名称为“用于评估结肠肿瘤的存在或风险的 方法”的中国专利申请(PCT申请号为PCT/US2013/072691，PCT申 请日为2013年12月02日)的分案申请。
交叉引用
本申请根据35U.S.C.§119(e)要求2012年11月30日提交的美 国临时申请号61/732,024和2013年3月5日提交的美国临时申请号 61/772,979的优先权，所有这些临时申请均通过引用而整体并入本文。
序列表
本申请包含序列表，该序列表已经以ASCII格式电子提交，且 通过引用而整体并入于此。所述ASCII副本在2013年11月27日创 建，被命名为36765-703.201_SL.txt，大小为783,936个字节。
发明背景
如本领域已知，基因组的信息内容作为DNA而携带。基因表 达的第一步是将DNA转录成mRNA。基因表达的第二步是从mRNA 合成多肽，使得mRNA的每三个核苷酸编码一个将组成多肽的氨基 酸残基。翻译后，多肽通常通过添加不同的化学基团如碳水化合物、 脂质和磷酸基团以及通过对特定肽键的蛋白水解裂解进行翻译后修 饰。这些化学修饰使多肽呈现独特的三维构象，从而形成成熟蛋白质。 虽然这些翻译后修饰不是由mRNA模板直接编码的，但它们是蛋白 质的关键特质，其通过改变整体构象和可用的相互作用位点来起到调节蛋白质功能的作用。此外，细胞内的蛋白质水平可反映个体是否处 于健康或疾病状态。因此，蛋白质是疾病状态、疾病的早期发作和疾 病风险的非常有价值的生物标志物来源。
mRNA和蛋白质均通过单独的途径不断地合成并降解。此外， 存在对合成和降解途径的多个水平的调节。鉴于此，在mRNA种类 的丰度与它们编码的蛋白质的实际量之间不存在简单的关联也就不 足为奇了(Anderson和Seilhamer,Electrophoresis 18:533-537；Gygi 等人,Mol.Cell.Biol.19:1720-1730,1999)。因此，尽管通常外推 mRNA水平以指示表达的蛋白质的水平，但蛋白质的最终水平并非必 需通过测量mRNA水平才可获得(Patton,J.Chromatogr.722:203-223, 1999；Patton等人,J.Biol.Chem.270:21404-21410(1995))。
因此，需要确定生物样品的蛋白质谱的方法。
发明内容
公开了用于以大于70％的灵敏度或大于70％的选择性检测受试 者的结肠的腺瘤、癌症或息肉的存在的方法。在各个实施方案中，所 述方法包括以下步骤：(a)从受试者获得血液样品；(b)裂解所述 血液样品中的蛋白质以提供包含肽的样品；(c)分析所述样品中至 少十种肽的存在；(d)将分析所述样品的结果与对照参考值进行比 较，从而以大于70％的灵敏度或大于70％的选择性确定存在结肠的腺 瘤或息肉的正或负得分。还公开了治疗受试者的结肠的腺瘤、癌症或 息肉的方法，该方法包括：(a)执行如本文所述的检测方法以得到 具有存在腺瘤、癌症或息肉的正得分的受试者；以及(b)进行用于 去除所述受试者的腺瘤或息肉组织的程序。
此外，公开了用于检测受试者的结肠的腺瘤或息肉的存在与否 的方法，其中所述受试者没有结肠的腺瘤或息肉的症状或家族史，所 述方法包括以下步骤：(a)从所述受试者获得生物样品；(b)对所 述生物样品进行关于一种或多种蛋白质和/或肽的存在和量的分析；(c) 将来自所述生物样品的一种或多种蛋白质和/或肽的存在和量与对照 参考值进行比较；以及(d)将一种或多种蛋白质和/或肽的存在和量 与所述受试者的腺瘤、癌症或息肉状态相关联。
此外，公开了用于检测在结肠镜检查得到阴性结果的受试者中 结肠的腺瘤、癌症或息肉的存在与否的方法，该方法包括以下步骤： (a)从基于结肠镜检查具有腺瘤、癌症或息肉的阴性诊断的受试者 获得生物样品；(b)对所述生物样品进行关于一种或多种蛋白质和/ 或肽的存在和量的分析；(c)将来自所述生物样品的一种或多种蛋 白质和/或肽的存在和量与对照参考值进行比较；以及(d)将一种或 多种蛋白质和/或肽的存在和量与所述受试者的腺瘤、癌症或息肉状态 相关联。
公开了用于检测先前治疗结肠的腺瘤、癌症或息肉的受试者中 结肠的腺瘤、癌症或息肉的复发或不存在的方法，该方法包括以下步 骤：(a)从先前治疗结肠的腺瘤、癌症或息肉的受试者获得生物样 品；(b)对所述生物样品进行关于一种或多种蛋白质和/或肽的存在 和量的分析；(c)将来自所述生物样品的一种或多种蛋白质和/或肽 的存在和量与对照参考值进行比较；以及(d)将一种或多种蛋白质 和/或肽的存在和量与所述受试者的腺瘤、癌症或息肉状态相关联。
此外，公开了针对诊断应用的蛋白质和/或肽检测方法，该方法 包括以下步骤：(a)从受试者获得生物样品；(b)对所述生物样品 进行关于一种或多种蛋白质和/或肽的存在和量的分析；(c)将来自 所述生物样品的一种或多种蛋白质和/或肽的存在和量与对照参考值 进行比较；以及(d)将一种或多种蛋白质和/或肽的存在和量与所述 受试者的诊断相关联；其中所述分析检测如本文公开的一种或多种蛋 白质、肽或分类器的存在和量。
此外，公开了用于执行如本文所述的方法的试剂盒，其中该试 剂盒包含：(a)用于从受试者采集样品的容器；(b)用于检测一种 或多种蛋白质或肽的工具(means)，或用于将所述容器转移至测试 设备的工具；以及(c)书面说明书。
最后，本公开提供了用于诊断、预测、预后和/或监测结肠疾病 的方法。还公开了用于诊断、预测、预后和/或监测受试者的结肠疾病 或结肠直肠癌的方法，该方法包括：测量来自受试者的生物样品中选 自下组的至少一种生物标志物：ACTB、ACTH、ANGT、SAHH、ALDR、 AKT1、ALBU、AL1A1、AL1B1、ALDOA、AMY2B、ANXA1、ANXA3、 ANXA4、ANXA5、APC、APOA1、APOC1、APOH、GDIR1、ATPB、 BANK1、MIC1、CA195、CO3、CO9、CAH1、CAH2、CALR、CAPG、 CD24、CD63、CDD、CEAM3、CEAM5、CEAM6、CGHB、CH3L1、 KCRB、CLC4D、CLUS、CNN1、COR1C、CRP、CSF1、CTNB1、 CATD、CATS、CATZ、CUL1、SYDC、DEF1、DEF3、DESM、DPP4、 DPYL2、DYHC1、ECH1、EF2、IF4A3、ENOA、EZRI、NIBL2、SEPR、 FBX4、FIBB、FIBG、FHL1、FLNA、FRMD3、FRIH、FRIL、FUCO、GBRA1、G3P、SYG、GDF15、GELS、GSTP1、HABP2、HGF、1A68、 HMGB1、ROA1、ROA2、HNRPF、HPT、HS90B、ENPL、GRP75、 HSPB1、CH60、SIAL、IFT74、IGF1、IGHA2、IL2RB、IL8、IL9、 RASK、K1C19、K2C8、LAMA2、LEG3、LMNB1、MARE1、MCM4、 MIF、MMP7、MMP9、CD20、MYL6、MYL9、NDKA、NNMT、A1AG1、 PCKGM、PDIA3、PDIA6、PDXK、PEBP1、PIPNA、KPYM、UROK、 IPYR、PRDX1、KPCD1、PRL、TMG4、PSME3、PTEN、FAK1、FAK2、 RBX1、REG4、RHOA、RHOB、RHOC、RSSA、RRBP1、S10AB、 S10AC、S10A8、S109、SAA1、SAA2、SEGN、SDCG3、DHSA、SBP1、 SELPL、SEP9、A1AT、AACT、ILEU、SPB6、SF3B3、SKP1、ADT2、 ISK1、SPON2、OSTP、SRC、STK11、HNRPQ、TAL1、TRFE、TSP1、 TIMP1、TKT、TSG6、TR10B、TNF6B、P53、TPM2、TCTP、TRAP1、 THTR、TBB1、UGDH、UGPA、VEGFA、VILI、VIME、VNN1、1433Z、 CCR5、FUCO及其组合。
还公开了用于诊断、预测、预后和/或监测受试者的结肠疾病或 结肠直肠癌的方法，该方法包括：测量来自所述受试者的生物样品中 选自SPB6、FRIL、P53、1A68、ENOA、TKT及其组合的至少一种 生物标志物。
公开了用于诊断、预测、预后和/或监测受试者的结肠疾病或结 肠直肠癌的方法，该方法包括：测量来自所述受试者的生物样品中选 自SPB6、FRIL、P53、1A68、ENOA、TKT、TSG6、TPM2、ADT2、 FHL1、CCR5、CEAM5、SPON2、1A68、RBX1、COR1C、VIME、 PSME3及其组合的至少一种生物标志物。
公开了用于诊断、预测、预后和/或监测受试者的结肠疾病或结 肠直肠癌的方法，该方法包括：测量来自所述受试者的生物样品中选 自SPB6、FRIL、P53、1A68、ENOA、TKT、TSG6、TPM2、ADT2、 FHL1、CCR5、CEAM5、SPON2、1A68、RBX1、COR1C、VIME、 PSME3、MIC1、STK11、IPYR、SBP1、PEBP1、CATD、HPT、ANXA5、 ALDOA、LAMA2、CATZ、ACTB、AACT及其组合的至少一种生物 标志物。
以下非限制性实施方案提供了本发明的示例性实例，但并不限制 本发明的范围。
1.一种以大于70％的灵敏度或大于70％的选择性检测受试者结 肠的腺瘤或息肉的存在的方法；所述方法包括以下步骤：
(a)从受试者获得血液样品；
(b)裂解所述血液样品中的蛋白质以提供包含肽的样品；
(c)分析所述样品中至少十种肽的存在；
(d)将分析所述样品的结果与对照参考值进行比较，从而以大 于70％的灵敏度或大于70％的选择性确定存在结肠的腺瘤或息肉的 正或负得分。
2.根据实施方案1所述的方法，其中所述灵敏度选自大于75％、 大于80％、大于85％、大于90％、大于95％以及大于99％。
3.根据实施方案1所述的方法，其中所述选择性选自大于75％、 大于80％、大于85％、大于90％、大于95％以及大于99％。
4.根据实施方案1所述的方法，其中所述选择性和所述灵敏度大 于90％。
5.根据实施方案1所述的方法，其中所述受试者无症状。
6.根据实施方案1所述的方法，其中所述受试者先前已接受针对 结肠息肉的治疗。
7.根据实施方案1所述的方法，其中所述分析步骤包括光谱分析、 质谱法、免疫分析、酶反应性分析及其组合。
8.根据实施方案1所述的方法，其中所述分析包括质谱法。
9.根据实施方案1所述的方法，其中所述至少十种肽选自图8的 中性质量分类器。
10.一种治疗受试者的结肠的腺瘤或息肉的方法，该方法包括：
(a)执行实施方案1所述的方法以得到具有存在腺瘤或息肉的正 得分的受试者；以及
(b)进行用于去除所述受试者的腺瘤或息肉组织的程序。
11.一种检测受试者的结肠的腺瘤或息肉的存在与否的方法，其 中所述受试者没有结肠的腺瘤或息肉的症状或家族史，所述方法包括 以下步骤：
(a)从所述受试者获得生物样品；
(b)对所述生物样品进行关于一种或多种蛋白质和/或肽的存在 和量的分析；
(c)将来自所述生物样品的一种或多种蛋白质和/或肽的存在和 量与对照参考值进行比较；以及
(d)将一种或多种蛋白质和/或肽的存在和量与所述受试者的腺 瘤或息肉状态相关联。
12.根据实施方案11所述的方法，其中所述方法实现了选自大于 70％、大于75％、大于80％、大于85％、大于90％、大于95％以及大 于99％的灵敏度。
13.根据实施方案11所述的方法，其中所述方法实现了选自大于 70％、大于75％、大于80％、大于85％、大于90％、大于95％以及大 于99％的特异性。
14.根据实施方案11所述的方法，其中所述方法实现了各自独立 地选自大于70％、大于75％、大于80％、大于85％、大于90％、大 于95％以及大于99％的灵敏度和特异性。
15.根据实施方案11所述的方法，进一步包括准备关于所述受试 者的报告，其中所述报告指示腺瘤或息肉的存在与否。
16.根据实施方案15所述的方法，其中所述报告指示息肉发展的 倾向或风险、细胞发育异常的程度、腺瘤性息肉的亚型或良性结肠肿 瘤疾病的亚型。
17.根据实施方案11所述的方法，其中所述方法检测腺瘤的存在 与否。
18.根据实施方案17所述的方法，其中所述腺瘤是腺瘤性息肉或 息肉样腺瘤。
19.根据实施方案18所述的方法，其中所述腺瘤性息肉或息肉样 腺瘤选自有蒂息肉和无蒂息肉。
20.根据实施方案18所述的方法，其中对所述腺瘤性息肉或息肉 样腺瘤根据细胞发育异常或恶变前的程度进行表征。
21.根据实施方案11所述的方法，其中所述方法进一步检测结肠 直肠癌的存在与否。
22.根据实施方案11所述的方法，其中所述方法不检测结肠直肠 癌的存在与否。
23.根据实施方案11所述的方法，其中不对结肠直肠癌的存在与 否进行确定。
24.根据实施方案11所述的方法，其中所述存在与否通过结肠镜 检查、成像和/或手术来确认。
25.根据实施方案11所述的方法，其中所述生物样品选自全血、 血清、血浆、血液成分、骨髓、唾液、脸颊拭子、尿、粪便、淋巴液、 CNS液和病变渗出物。
26.根据实施方案25所述的方法，其中所述生物样品选自全血、 血清和血浆。
27.根据实施方案11所述的方法，其中所述受试者无症状。
28.根据实施方案11所述的方法，其中所述受试者为18至49岁。
29.根据实施方案11所述的方法，其中所述受试者先前未接受过 结肠镜检查。
30.根据实施方案11所述的方法，其中所述受试者没有结肠直肠 癌的症状，没有结肠直肠癌家族史，并且没有经识别的结肠直肠癌风 险因素。
31.根据实施方案11所述的方法，其中所述受试者没有结肠直肠 癌的症状，没有结肠直肠癌家族史，并且没有除年龄之外的经识别的 结肠直肠癌风险因素。
32.根据实施方案11所述的方法，其中步骤(b)中的所述分析 包括选自光谱分析、质谱法、免疫分析和酶反应性分析的方法。
33.根据实施方案32所述的方法，其中所述分析为质谱法。
34.根据实施方案32所述的方法，其中所述免疫分析包括酶联免 疫吸附测定或放射免疫测定。
35.根据实施方案32所述的方法，其中所述免疫分析包括免疫印 迹、免疫扩散、免疫电泳或免疫沉淀。
36.根据实施方案32所述的方法，其中所述免疫分析包括免疫染 色和/或流式细胞术分析。
37.根据实施方案11所述的方法，其中所述对照参考为相同生物 样品中的一组一种或多种非重叠蛋白质和/或肽的存在和量。
38.根据实施方案11所述的方法，其中所述对照参考为从一个或 多个存在结肠的腺瘤或息肉的受试者获得的重叠的一组蛋白质和/或 肽的存在和量。
39.根据实施方案11所述的方法，其中所述对照参考为从一个或 多个不存在结肠的腺瘤或息肉的受试者获得的重叠的一组蛋白质和/ 或肽的存在和量。
40.根据实施方案11所述的方法，其中所述分析检测一定数目的 蛋白质或多肽的存在和量，其中所述数目选自至少2种、至少5种、 至少10种、至少50种、至少100种以及至少1000种。
41.根据实施方案11所述的方法，其中所述分析检测下组中的一 种或多种的存在和量：
i)选自SCDC26(CD26)、CEA分子5(CEACAM5)、CA195(CCR5)、 CA19-9、M2PK(PKM2)、TIMP1、P-选择蛋白(SELPLG)、VEGFA、 HcGB(CGB)、绒毛蛋白、TATI(SPINK1)、A-L-岩藻糖苷酶(FUCA2)、 ANXA5、GAPDH、PKM2、ANXA4、GARS、RRBP1、KRT8、SYNCRIP、 S100A9、ANXA3、CAPG、HNRNPF、PPA1、NME1、PSME3、AHCY、 TPT1、HSPB1和RPSA、和/或图9中的蛋白质，以及它们的组合的 一种或多种蛋白质；
ii)SCDC26(CD26)、CEA分子5(CEACAM5)、CA195(CCR5)、 CA19-9、M2PK(PKM2)、TIMP1、P-选择蛋白(SELPLG)、VEGFA、 HcGB(CGB)、绒毛蛋白、TATI(SPINK1)、A-L-岩藻糖苷酶(FUCA2)、 ANXA5、GAPDH、PKM2、ANXA4、GARS、RRBP1、KRT8、SYNCRIP、 S100A9、ANXA3、CAPG、HNRNPF、PPA1、NME1、PSME3、AHCY、 TPT1、HSPB1和RPSA、和/或图9中的蛋白质，以及它们的组合的 一种或多种肽片段；
iii)与SCDC26(CD26)、CEA分子5(CEACAM5)、CA195(CCR5)、 CA19-9、M2PK(PKM2)、TIMP1、P-选择蛋白(SELPLG)、VEGFA、 HcGB(CGB)、绒毛蛋白、TATI(SPINK1)、A-L-岩藻糖苷酶(FUCA2)、 ANXA5、GAPDH、PKM2、ANXA4、GARS、RRBP1、KRT8、SYNCRIP、 S100A9、ANXA3、CAPG、HNRNPF、PPA1、NME1、PSME3、AHCY、 TPT1、HSPB1和RPSA、和/或图9中的蛋白质，以及它们的组合具 有序列同源性的一种或多种肽，其中所述序列同源性选自大于75％、 大于80％、大于85％、大于90％、大于95％及大于99％；以及
iv)SCDC26(CD26)、CEA分子5(CEACAM5)、CA195(CCR5)、 CA19-9、M2PK(PKM2)、TIMP1、P-选择蛋白(SELPLG)、VEGFA、 HcGB(CGB)、绒毛蛋白、TATI(SPINK1)、A-L-岩藻糖苷酶(FUCA2)、 ANXA5、GAPDH、PKM2、ANXA4、GARS、RRBP1、KRT8、SYNCRIP、 S100A9、ANXA3、CAPG、HNRNPF、PPA1、NME1、PSME3、AHCY、 TPT1、HSPB1和RPSA、和/或图9中的蛋白质，以及它们的组合的 一种或多种结合配偶体。
42.根据实施方案11所述的方法，其中所述分析检测图7或图8 中的一个或多个中性质量簇的存在和/或量。
43.根据实施方案42所述的方法，其中所述分析检测图7或图8 中的一定数目的中性质量簇的存在和/或量，其中所述数目选自至少2 个、至少5个、至少10个、至少50个、至少100个、至少200个、 至少500个以及至少1000个。
44.根据实施方案42所述的方法，其中所述分析检测图7或图8 中的一定数目的中性质量簇的存在和/或量，其中所述数目为至少一个， 并选自少于5个、少于10个、少于50个、少于100个、少于200个、 少于500个以及少于1000个。
45.根据实施方案42所述的方法，其中所述分析检测图7或图8 中的一定数目的中性质量簇的存在和/或量，其中所述数目选自10-50 个、60-100个、150-300个、400-600个以及800-1000个，包含端值。
46.根据实施方案42所述的方法，其中所述中性质量簇在根据针 对分割分类器的70/30训练/测试进行测试时具有下述分类器频率，所 述分类器频率选自至少3/50、至少10/50、至少20/50、至少30/50以 及至少40/50。
47.根据实施方案42所述的方法，其中所述分析检测从中得到图 7或图8中的一个或多个中性质量簇的蛋白质或肽的存在和/或量。
48.根据实施方案11所述的方法，进一步包括：
(e)对所述生物样品进行关于选自代谢物、DNA序列、RNA序 列及其组合的一种或多种分析物的存在和量的分析；以及
(f)将所述分析物的存在和量与对照参考值进行比较；以及
(g)将所述分析物的存在和量与所述受试者的腺瘤或息肉状态 相关联。
49.一种检测在结肠镜检查得到阴性结果的受试者中结肠的腺瘤 或息肉的存在与否的方法，所述方法包括以下步骤：
(a)从基于结肠镜检查具有腺瘤或息肉的阴性诊断的受试者获得 生物样品；
(b)对所述生物样品进行关于一种或多种蛋白质和/或肽的存在 和量的分析；
(c)将来自所述生物样品的一种或多种蛋白质和/或肽的存在和 量与对照参考值进行比较；以及
(d)将一种或多种蛋白质和/或肽的存在和量与所述受试者的腺 瘤或息肉状态相关联。
50.根据实施方案49所述的方法，其中所述方法实现了选自大于 70％、大于75％、大于80％、大于85％、大于90％、大于95％以及大 于99％的灵敏度。
51.根据实施方案49所述的方法，其中所述方法实现了选自大于 70％、大于75％、大于80％、大于85％、大于90％、大于95％以及大 于99％的特异性。
52.根据实施方案49所述的方法，其中所述方法实现了各自独立 地选自大于70％、大于75％、大于80％、大于85％、大于90％、大 于95％以及大于99％的灵敏度和特异性。
53.根据实施方案49所述的方法，进一步包括准备关于所述受试 者的报告，其中所述报告指示腺瘤或息肉的存在与否。
54.根据实施方案53所述的方法，其中所述报告指示息肉发展的 倾向或风险、细胞发育异常的程度、腺瘤性息肉的亚型或良性结肠肿 瘤疾病的亚型。
55.根据实施方案49所述的方法，其中所述方法检测腺瘤的存在 与否。
56.根据实施方案55所述的方法，其中所述腺瘤是腺瘤性息肉或 息肉样腺瘤。
57.根据实施方案56所述的方法，其中所述腺瘤性息肉或息肉样 腺瘤选自有蒂息肉和无蒂息肉。
58.根据实施方案56所述的方法，其中对所述腺瘤性息肉或息肉 样腺瘤根据细胞发育异常或恶变前的程度进行表征。
59.根据实施方案49所述的方法，其中所述方法进一步检测结肠 直肠癌的存在与否。
60.根据实施方案49所述的方法，其中所述方法不检测结肠直肠 癌的存在与否。
61.根据实施方案49所述的方法，其中不对结肠直肠癌的存在与 否进行确定。
62.根据实施方案49所述的方法，其中所述存在与否通过结肠镜 检查、成像和/或手术来确认。
63.根据实施方案49所述的方法，其中所述生物样品选自全血、 血清、血浆、血液成分、骨髓、唾液、脸颊拭子、尿、粪便、淋巴液、 CNS液和病变渗出物。
64.根据实施方案63所述的方法，其中所述生物样品选自全血、 血清和血浆。
65.根据实施方案49所述的方法，其中所述受试者无症状。
66.根据实施方案49所述的方法，其中所述受试者为18至49岁。
67.根据实施方案49所述的方法，其中所述受试者没有结肠直肠 癌的症状，没有结肠直肠癌家族史，并且没有经识别的结肠直肠癌风 险因素。
68.根据实施方案49所述的方法，其中所述受试者没有结肠直肠 癌的症状，没有结肠直肠癌家族史，并且没有除年龄之外的经识别的 结肠直肠癌风险因素。
69.根据实施方案49所述的方法，其中步骤(b)中的所述分析 包括选自光谱分析、质谱法、免疫分析和酶反应性分析的方法。
70.根据实施方案69所述的方法，其中所述分析为质谱法。
71.根据实施方案69所述的方法，其中所述免疫分析包括酶联免 疫吸附测定或放射免疫测定。
72.根据实施方案69所述的方法，其中所述免疫分析包括免疫印 迹、免疫扩散、免疫电泳或免疫沉淀。
73.根据实施方案69所述的方法，其中所述免疫分析包括免疫染 色和/或流式细胞术分析。
74.根据实施方案49所述的方法，其中所述对照参考为相同生物 样品中的一组一种或多种非重叠蛋白质和/或肽的存在和量。
75.根据实施方案49所述的方法，其中所述对照参考为从一个或 多个存在结肠的腺瘤或息肉的受试者获得的重叠的一组蛋白质和/或 肽的存在和量。
76.根据实施方案49所述的方法，其中所述对照参考为从一个或 多个不存在结肠的腺瘤或息肉的受试者获得的重叠的一组蛋白质和/ 或肽的存在和量。
77.根据实施方案49所述的方法，其中所述分析检测一定数目的 蛋白质或多肽的存在和量，其中所述数目选自至少2种、至少5种、 至少10种、至少50种、至少100种以及至少1000种。
78.根据实施方案49所述的方法，其中所述分析检测下组中的一 种或多种的存在和量：
i)选自SCDC26(CD26)、CEA分子5(CEACAM5)、CA195(CCR5)、 CA19-9、M2PK(PKM2)、TIMP1、P-选择蛋白(SELPLG)、VEGFA、 HcGB(CGB)、绒毛蛋白、TATI(SPINK1)、A-L-岩藻糖苷酶(FUCA2)、 ANXA5、GAPDH、PKM2、ANXA4、GARS、RRBP1、KRT8、SYNCRIP、 S100A9、ANXA3、CAPG、HNRNPF、PPA1、NME1、PSME3、AHCY、 TPT1、HSPB1和RPSA、和/或图9中的蛋白质，以及它们的组合的 一种或多种蛋白质；
ii)SCDC26(CD26)、CEA分子5(CEACAM5)、CA195(CCR5)、 CA19-9、M2PK(PKM2)、TIMP1、P-选择蛋白(SELPLG)、VEGFA、 HcGB(CGB)、绒毛蛋白、TATI(SPINK1)、A-L-岩藻糖苷酶(FUCA2)、 ANXA5、GAPDH、PKM2、ANXA4、GARS、RRBP1、KRT8、SYNCRIP、 S100A9、ANXA3、CAPG、HNRNPF、PPA1、NME1、PSME3、AHCY、 TPT1、HSPB1和RPSA、和/或图9中的蛋白质，以及它们的组合的 一种或多种肽片段；
iii)与SCDC26(CD26)、CEA分子5(CEACAM5)、CA195(CCR5)、 CA19-9、M2PK(PKM2)、TIMP1、P-选择蛋白(SELPLG)、VEGFA、HcGB(CGB)、绒毛蛋白、TATI(SPINK1)、A-L-岩藻糖苷酶(FUCA2)、 ANXA5、GAPDH、PKM2、ANXA4、GARS、RRBP1、KRT8、SYNCRIP、 S100A9、ANXA3、CAPG、HNRNPF、PPA1、NME1、PSME3、AHCY、 TPT1、HSPB1和RPSA、和/或图9中的蛋白质，以及它们的组合具 有序列同源性的一种或多种肽，其中所述序列同源性选自大于75％、 大于80％、大于85％、大于90％、大于95％及大于99％；以及
iv)SCDC26(CD26)、CEA分子5(CEACAM5)、CA195(CCR5)、 CA19-9、M2PK(PKM2)、TIMP1、P-选择蛋白(SELPLG)、VEGFA、 HcGB(CGB)、绒毛蛋白、TATI(SPINK1)、A-L-岩藻糖苷酶(FUCA2)、 ANXA5、GAPDH、PKM2、ANXA4、GARS、RRBP1、KRT8、SYNCRIP、 S100A9、ANXA3、CAPG、HNRNPF、PPA1、NME1、PSME3、AHCY、 TPT1、HSPB1和RPSA、和/或图9中的蛋白质以及它们的组合的一 种或多种结合配偶体。
79.根据实施方案49所述的方法，其中所述分析检测图7或图8 中的一个或多个中性质量簇的存在和/或量。
80.根据实施方案79所述的方法，其中所述分析检测图7或图8 中的一定数目的中性质量簇的存在和/或量，其中所述数目选自至少2 个、至少5个、至少10个、至少50个、至少100个、至少200个、 至少500个以及至少1000个。
81.根据实施方案79所述的方法，其中所述分析检测图7或图8 中的一定数目的中性质量簇的存在和/或量，其中所述数目为至少一个， 并选自少于5个、少于10个、少于50个、少于100个、少于200个、 少于500个以及少于1000个。
82.根据实施方案79所述的方法，其中所述分析检测图7或图8 中的一定数目的中性质量簇的存在和/或量，其中所述数目选自10-50 个、60-100个、150-300个、400-600个以及800-1000个，包含端值。
83.根据实施方案79所述的方法，其中所述中性质量簇在根据针 对分割分类器的70/30训练/测试进行测试时具有下述分类器频率，所 述分类器频率选自至少3/50、至少10/50、至少20/50、至少30/50以 及至少40/50。
84.根据实施方案79所述的方法，其中所述分析检测从中得到图 7或图8中的一个或多个中性质量簇的蛋白质或肽的存在和/或量。
85.根据实施方案79所述的方法，进一步包括：
(e)对所述生物样品进行关于选自代谢物、DNA序列、RNA序 列及其组合的一种或多种分析物的存在和量的分析；以及
(f)将所述分析物的存在和量与对照参考值进行比较；以及
(g)将所述分析物的存在和量与所述受试者的腺瘤或息肉状态 相关联。
86.一种检测先前治疗结肠的腺瘤或息肉的受试者中结肠的腺瘤 或息肉的复发或不存在的方法，该方法包括以下步骤：
(a)从先前治疗结肠的腺瘤或息肉的受试者获得生物样品；
(b)对所述生物样品进行关于一种或多种蛋白质和/或肽的存在 和量的分析；
(c)将来自所述生物样品的一种或多种蛋白质和/或肽的存在和 量与对照参考值进行比较；以及
(d)将一种或多种蛋白质和/或肽的存在和量与所述受试者的腺 瘤或息肉状态相关联。
87.根据实施方案86所述的方法，其中所述方法实现了选自大于 70％、大于75％、大于80％、大于85％、大于90％、大于95％以及大 于99％的灵敏度。
88.根据实施方案86所述的方法，其中所述方法实现了选自大于 70％、大于75％、大于80％、大于85％、大于90％、大于95％以及大 于99％的特异性。
89.根据实施方案86所述的方法，其中所述方法实现了各自独立 地选自大于70％、大于75％、大于80％、大于85％、大于90％、大 于95％以及大于99％的灵敏度和特异性。
90.根据实施方案86所述的方法，进一步包括准备关于所述受试 者的报告，其中所述报告指示腺瘤或息肉的存在与否。
91.根据实施方案90所述的方法，其中所述报告指示息肉发展的 倾向或风险、细胞发育异常的程度、腺瘤性息肉的亚型或良性结肠肿 瘤疾病的亚型。
92.根据实施方案86所述的方法，其中所述方法检测腺瘤的存在 与否。
93.根据实施方案92所述的方法，其中所述腺瘤是腺瘤性息肉或 息肉样腺瘤。
94.根据实施方案93所述的方法，其中所述腺瘤性息肉或息肉样 腺瘤选自有蒂息肉和无蒂息肉。
95.根据实施方案93所述的方法，其中对所述腺瘤性息肉或息肉 样腺瘤根据细胞发育异常或恶变前的程度进行表征。
96.根据实施方案86所述的方法，其中所述方法进一步检测结肠 直肠癌的存在与否。
97.根据实施方案86所述的方法，其中所述方法不检测结肠直肠 癌的存在与否。
98.根据实施方案86所述的方法，其中不对结肠直肠癌的存在与 否进行确定。
99.根据实施方案86所述的方法，其中所述存在与否通过结肠镜 检查、成像和/或手术来确认。
100.根据实施方案86所述的方法，其中所述生物样品选自全血、 血清、血浆、血液成分、骨髓、唾液、脸颊拭子、尿、粪便、淋巴液、 CNS液和病变渗出物。
101.根据实施方案100所述的方法，其中所述生物样品选自全血、 血清和血浆。
102.根据实施方案86所述的方法，其中所述受试者无症状。
103.根据实施方案86所述的方法，其中所述受试者为18至49 岁。
104.根据实施方案86所述的方法，其中所述受试者没有结肠直 肠癌的症状，没有结肠直肠癌家族史，并且没有经识别的结肠直肠癌 风险因素。
105.根据实施方案86所述的方法，其中所述受试者没有结肠直 肠癌的症状，没有结肠直肠癌家族史，并且没有除年龄之外的经识别 的结肠直肠癌风险因素。
106.根据实施方案86所述的方法，其中步骤(b)中的所述分析 包括选自光谱分析、质谱法、免疫分析和酶反应性分析的方法。
107.根据实施方案106所述的方法，其中所述分析为质谱法。
108.根据实施方案106所述的方法，其中所述免疫分析包括酶联 免疫吸附测定或放射免疫测定。
109.根据实施方案106所述的方法，其中所述免疫分析包括免疫 印迹、免疫扩散、免疫电泳或免疫沉淀。
110.根据实施方案106所述的方法，其中所述免疫分析包括免疫 染色和/或流式细胞术分析。
111.根据实施方案86所述的方法，其中所述对照参考为相同生 物样品中的一组一种或多种非重叠蛋白质和/或肽的存在和量。
112.根据实施方案86所述的方法，其中所述对照参考为从一个 或多个存在结肠的腺瘤或息肉的受试者获得的重叠的一组蛋白质和/ 或肽的存在和量。
113.根据实施方案86所述的方法，其中所述对照参考为从一个 或多个不存在结肠的腺瘤或息肉的受试者获得的重叠的一组蛋白质 和/或肽的存在和量。
114.根据实施方案86所述的方法，其中所述分析检测一定数目 的蛋白质或多肽的存在和量，其中所述数目选自至少2种、至少5种、 至少10种、至少50种、至少100种以及至少1000种。
115.根据实施方案86所述的方法，其中所述分析检测下组中的 一种或多种的存在和量：
i)选自SCDC26(CD26)、CEA分子5(CEACAM5)、CA195(CCR5)、 CA19-9、M2PK(PKM2)、TIMP1、P-选择蛋白(SELPLG)、VEGFA、 HcGB(CGB)、绒毛蛋白、TATI(SPINK1)、A-L-岩藻糖苷酶(FUCA2)、ANXA5、GAPDH、PKM2、ANXA4、GARS、RRBP1、KRT8、SYNCRIP、 S100A9、ANXA3、CAPG、HNRNPF、PPA1、NME1、PSME3、AHCY、 TPT1、HSPB1和RPSA、和/或图9中的蛋白质，以及它们的组合的 一种或多种蛋白质；
ii)SCDC26(CD26)、CEA分子5(CEACAM5)、CA195(CCR5)、 CA19-9、M2PK(PKM2)、TIMP1、P-选择蛋白(SELPLG)、VEGFA、 HcGB(CGB)、绒毛蛋白、TATI(SPINK1)、A-L-岩藻糖苷酶(FUCA2)、 ANXA5、GAPDH、PKM2、ANXA4、GARS、RRBP1、KRT8、SYNCRIP、 S100A9、ANXA3、CAPG、HNRNPF、PPA1、NME1、PSME3、AHCY、 TPT1、HSPB1和RPSA、和/或图9中的蛋白质，以及它们的组合的 一种或多种肽片段；
iii)与SCDC26(CD26)、CEA分子5(CEACAM5)、CA195(CCR5)、 CA19-9、M2PK(PKM2)、TIMP1、P-选择蛋白(SELPLG)、VEGFA、 HcGB(CGB)、绒毛蛋白、TATI(SPINK1)、A-L-岩藻糖苷酶(FUCA2)、 ANXA5、GAPDH、PKM2、ANXA4、GARS、RRBP1、KRT8、SYNCRIP、 S100A9、ANXA3、CAPG、HNRNPF、PPA1、NME1、PSME3、AHCY、 TPT1、HSPB1和RPSA、和/或图9中的蛋白质，以及它们的组合具 有序列同源性的一种或多种肽，其中所述序列同源性选自大于75％、 大于80％、大于85％、大于90％、大于95％及大于99％；以及
iv)SCDC26(CD26)、CEA分子5(CEACAM5)、CA195(CCR5)、 CA19-9、M2PK(PKM2)、TIMP1、P-选择蛋白(SELPLG)、VEGFA、 HcGB(CGB)、绒毛蛋白、TATI(SPINK1)、A-L-岩藻糖苷酶(FUCA2)和ANXA5、GAPDH、PKM2、ANXA4、GARS、RRBP1、KRT8、SYNCRIP、 S100A9、ANXA3、CAPG、HNRNPF、PPA1、NME1、PSME3、AHCY、 TPT1、HSPB1和RPSA、和/或图9中的蛋白质，以及它们的组合的 一种或多种结合配偶体。
116.根据实施方案86所述的方法，其中所述分析检测图7或图 8中的一个或多个中性质量簇的存在和/或量。
117.根据实施方案116所述的方法，其中所述分析检测图7或图8中的一定数目的中性质量簇的存在和/或量，其中所述数目选自至少 2个、至少5个、至少10个、至少50个、至少100个、至少200个、 至少500个以及至少1000个。
118.根据实施方案116所述的方法，其中所述分析检测图7或图 8中的一定数目的中性质量簇的存在和/或量，其中所述数目为至少一 个，并选自少于5个、少于10个、少于50个、少于100个、少于200 个、少于500个以及少于1000个。
119.根据实施方案116所述的方法，其中所述分析检测图7或图 8中的一定数目的中性质量簇的存在和/或量，其中所述数目选自 10-50个、60-100个、150-300个、400-600个以及800-1000个，包含 端值。
120.根据实施方案116所述的方法，其中所述中性质量簇在根据 针对分割分类器的70/30训练/测试进行测试时具有下述分类器频率， 所述分类器频率选自至少3/50、至少10/50、至少20/50、至少30/50 以及至少40/50。
121.根据实施方案116所述的方法，其中所述分析检测从中得到 图7或图8中的一个或多个中性质量簇的蛋白质或肽的存在和/或量。
122.根据实施方案86所述的方法，进一步包括：
(e)对所述生物样品进行关于选自代谢物、DNA序列、RNA序 列以及它们的组合的一种或多种分析物的存在和量的分析；
(f)将所述分析物的存在和量与对照参考值进行比较；以及
(g)将所述分析物的存在和量与所述受试者的腺瘤或息肉状态 相关联。
123.根据实施方案86所述的方法，其中所述受试者先前通过去 除息肉而治疗结肠息肉。
124.根据实施方案86所述的方法，其中所述受试者先前通过从 结肠中去除至少1厘米的组织进行治疗。
125.一种针对诊断应用的蛋白质和/或肽检测方法，该方法包括 以下步骤：
(a)从受试者获得生物样品；
(b)对所述生物样品进行关于一种或多种蛋白质和/或肽的存在 和量的分析；
(c)将来自所述生物样品的一种或多种蛋白质和/或肽的存在和 量与对照参考值进行比较；以及
(d)将一种或多种蛋白质和/或肽的存在和量与所述受试者的诊 断相关联；
其中所述分析检测下组中的一种或多种的存在和量：
i)选自SCDC26(CD26)、CEA分子5(CEACAM5)、CA195(CCR5)、 CA19-9、M2PK(PKM2)、TIMP1、P-选择蛋白(SELPLG)、VEGFA、 HcGB(CGB)、绒毛蛋白、TATI(SPINK1)、A-L-岩藻糖苷酶(FUCA2)、 ANXA5、GAPDH、PKM2、ANXA4、GARS、RRBP1、KRT8、SYNCRIP、 S100A9、ANXA3、CAPG、HNRNPF、PPA1、NME1、PSME3、AHCY、 TPT1、HSPB1和RPSA、和/或图9中的蛋白质，以及它们的组合的 一种或多种蛋白质；
ii)SCDC26(CD26)、CEA分子5(CEACAM5)、CA195(CCR5)、 CA19-9、M2PK(PKM2)、TIMP1、P-选择蛋白(SELPLG)、VEGFA、 HcGB(CGB)、绒毛蛋白、TATI(SPINK1)、A-L-岩藻糖苷酶(FUCA2)和ANXA5、GAPDH、PKM2、ANXA4、GARS、RRBP1、KRT8、SYNCRIP、 S100A9、ANXA3、CAPG、HNRNPF、PPA1、NME1、PSME3、AHCY、 TPT1、HSPB1和RPSA、和/或图9中的蛋白质，以及它们的组合的 一种或多种肽片段；
iii)与SCDC26(CD26)、CEA分子5(CEACAM5)、CA195(CCR5)、 CA19-9、M2PK(PKM2)、TIMP1、P-选择蛋白(SELPLG)、VEGFA、 HcGB(CGB)、绒毛蛋白、TATI(SPINK1)、A-L-岩藻糖苷酶(FUCA2)、 ANXA5、GAPDH、PKM2、ANXA4、GARS、RRBP1、KRT8、SYNCRIP、 S100A9、ANXA3、CAPG、HNRNPF、PPA1、NME1、PSME3、AHCY、 TPT1、HSPB1和RPSA、和/或图9中的蛋白质，以及它们的组合具 有序列同源性的一种或多种肽，其中所述序列同源性选自大于75％、 大于80％、大于85％、大于90％、大于95％及大于99％；
iv)SCDC26(CD26)、CEA分子5(CEACAM5)、CA195(CCR5)、 CA19-9、M2PK(PKM2)、TIMP1、P-选择蛋白(SELPLG)、VEGFA、 HcGB(CGB)、绒毛蛋白、TATI(SPINK1)、A-L-岩藻糖苷酶(FUCA2)和ANXA5、GAPDH、PKM2、ANXA4、GARS、RRBP1、KRT8、SYNCRIP、 S100A9、ANXA3、CAPG、HNRNPF、PPA1、NME1、PSME3、AHCY、 TPT1、HSPB1和RPSA、和/或图9中的蛋白质，以及它们的组合的 一种或多种结合配偶体；以及
v)从中得到图7或图8中的一个或多个中性质量簇的蛋白质或 肽。
126.根据实施方案125所述的方法，其中所述诊断为选自结肠的 腺瘤、息肉、结肠直肠癌及其组合的病况的存在与否。
127.根据实施方案125所述的方法，进一步包括通过以下步骤确 定步骤(b)中的所述量：
(b1)使所述生物样品或其部分与对第一肽具有特异性的第一抗 肽抗体接触；
(b2)使所述生物样品或其部分与对第二肽具有特异性的第二抗 肽抗体接触，其中所述第二抗肽抗体不同于所述第一抗肽抗体；
(b3)将被所述第一和第二抗肽抗体结合的肽与未结合的肽分离；
(b4)使用质谱法、流式细胞术、非重叠激发光谱、Western分 析、酶联免疫吸附测定、密度测定法或其组合来检测和/或测量被所述 第一和第二抗肽抗体结合的所述肽的量。
128.根据实施方案127所述的方法，其中所述生物样品或其部分 为所述生物样品的蛋白水解消化物。
129.根据实施方案127所述的方法，其中步骤(b4)包括质谱法。
130.一种用于执行根据实施方案1-129中任一项所述的方法的试 剂盒：
(a)用于从受试者采集样品的容器；
(b)用于检测一种或多种蛋白质或肽的工具，或用于将所述容 器转移至测试设备的工具；以及
(c)书面说明书。
131.根据实施方案130所述的试剂盒，其中所述用于检测一种或 多种蛋白质或肽的工具包含与下组中的一种或多种结合的一种或多 种抗体：
i)选自SCDC26(CD26)、CEA分子5(CEACAM5)、CA195(CCR5)、 CA19-9、M2PK(PKM2)、TIMP1、P-选择蛋白(SELPLG)、VEGFA、 HcGB(CGB)、绒毛蛋白、TATI(SPINK1)、A-L-岩藻糖苷酶(FUCA2)、 ANXA5、GAPDH、PKM2、ANXA4、GARS、RRBP1、KRT8、SYNCRIP、 S100A9、ANXA3、CAPG、HNRNPF、PPA1、NME1、PSME3、AHCY、 TPT1、HSPB1和RPSA、和/或图9中的蛋白质，以及它们的组合的 一种或多种蛋白质；
ii)SCDC26(CD26)、CEA分子5(CEACAM5)、CA195(CCR5)、 CA19-9、M2PK(PKM2)、TIMP1、P-选择蛋白(SELPLG)、VEGFA、 HcGB(CGB)、绒毛蛋白、TATI(SPINK1)、A-L-岩藻糖苷酶(FUCA2)和ANXA5、GAPDH、PKM2、ANXA4、GARS、RRBP1、KRT8、SYNCRIP、 S100A9、ANXA3、CAPG、HNRNPF、PPA1、NME1、PSME3、AHCY、 TPT1、HSPB1和RPSA、和/或图9中的蛋白质，以及它们的组合的 一种或多种肽片段；
iii)与SCDC26(CD26)、CEA分子5(CEACAM5)、CA195(CCR5)、 CA19-9、M2PK(PKM2)、TIMP1、P-选择蛋白(SELPLG)、VEGFA、 HcGB(CGB)、绒毛蛋白、TATI(SPINK1)、A-L-岩藻糖苷酶(FUCA2)、 ANXA5、GAPDH、PKM2、ANXA4、GARS、RRBP1、KRT8、SYNCRIP、 S100A9、ANXA3、CAPG、HNRNPF、PPA1、NME1、PSME3、AHCY、 TPT1、HSPB1和RPSA、和/或图9中的蛋白质，以及它们的组合具 有序列同源性的一种或多种肽，其中所述序列同源性选自大于75％、 大于80％、大于85％、大于90％、大于95％及大于99％；
iv)SCDC26(CD26)、CEA分子5(CEACAM5)、CA195(CCR5)、 CA19-9、M2PK(PKM2)、TIMP1、P-选择蛋白(SELPLG)、VEGFA、HcGB(CGB)、绒毛蛋白、TATI(SPINK1)、A-L-岩藻糖苷酶(FUCA2)、ANXA5、GAPDH、PKM2、ANXA4、GARS、RRBP1、KRT8、SYNCRIP、 S100A9、ANXA3、CAPG、HNRNPF、PPA1、NME1、PSME3、AHCY、 TPT1、HSPB1和RPSA、和/或图9中的蛋白质，以及它们的组合的 一种或多种结合配偶体；以及
v)从中得到图7或图8中的一个或多个中性质量簇的蛋白质或 肽。
132.根据实施方案131所述的试剂盒，其中一种或多种抗体各自 用标记物进行标记。
133.根据实施方案132所述的试剂盒，其中所述标记物选自放射 性标记物、荧光标记物、酶、化学发光标签及其组合。
134.根据实施方案131所述的试剂盒，其中所述抗体被包装在水 性介质中或以冻干形式包装。
135.根据实施方案130所述的试剂盒，其中所述用于检测一种或 多种蛋白质或肽的工具包括酶联免疫吸附测定。
136.一种用于诊断、预测、预后和/或监测受试者的结肠疾病的 方法，该方法包括：测量来自所述受试者的生物样品中选自下组的至 少一种生物标志物：ACTB、ACTH、ANGT、SAHH、ALDR、AKT1、 ALBU、AL1A1、AL1B1、ALDOA、AMY2B、ANXA1、ANXA3、 ANXA4、ANXA5、APC、APOA1、APOC1、APOH、GDIR1、ATPB、 BANK1、MIC1、CA195、CO3、CO9、CAH1、CAH2、CALR、CAPG、CD24、CD63、CDD、CEAM3、CEAM5、CEAM6、CGHB、CH3L1、 KCRB、CLC4D、CLUS、CNN1、COR1C、CRP、CSF1、CTNB1、 CATD、CATS、CATZ、CUL1、SYDC、DEF1、DEF3、DESM、DPP4、 DPYL2、DYHC1、ECH1、EF2、IF4A3、ENOA、EZRI、NIBL2、SEPR、 FBX4、FIBB、FIBG、FHL1、FLNA、FRMD3、FRIH、FRIL、FUCO、 GBRA1、G3P、SYG、GDF15、GELS、GSTP1、HABP2、HGF、1A68、 HMGB1、ROA1、ROA2、HNRPF、HPT、HS90B、ENPL、GRP75、 HSPB1、CH60、SIAL、IFT74、IGF1、IGHA2、IL2RB、IL8、IL9、RASK、K1C19、K2C8、LAMA2、LEG3、LMNB1、MARE1、MCM4、 MIF、MMP7、MMP9、CD20、MYL6、MYL9、NDKA、NNMT、A1AG1、 PCKGM、PDIA3、PDIA6、PDXK、PEBP1、PIPNA、KPYM、UROK、 IPYR、PRDX1、KPCD1、PRL、TMG4、PSME3、PTEN、FAK1、FAK2、 RBX1、REG4、RHOA、RHOB、RHOC、RSSA、RRBP1、S10AB、S10AC、S10A8、S109、SAA1、SAA2、SEGN、SDCG3、DHSA、SBP1、 SELPL、SEP9、A1AT、AACT、ILEU、SPB6、SF3B3、SKP1、ADT2、 ISK1、SPON2、OSTP、SRC、STK11、HNRPQ、TAL1、TRFE、TSP1、 TIMP1、TKT、TSG6、TR10B、TNF6B、P53、TPM2、TCTP、TRAP1、 THTR、TBB1、UGDH、UGPA、VEGFA、VILI、VIME、VNN1、1433Z、 CCR5、FUCO及其组合。
137.一种用于诊断、预测、预后和/或监测受试者的结肠疾病的 方法，该方法包括：测量来自所述受试者的生物样品中选自SPB6、 FRIL、P53、1A68、ENOA、TKT及其组合的至少一种生物标志物。
138.一种用于诊断、预测、预后和/或监测受试者的结肠疾病的 方法，该方法包括：测量来自所述受试者的生物样品中选自SPB6、 FRIL、P53、1A68、ENOA、TKT、TSG6、TPM2、ADT2、FHL1、 CCR5、CEAM5、SPON2、1A68、RBX1、COR1C、VIME、PSME3 及其组合的至少一种生物标志物。
139.一种用于诊断、预测、预后和/或监测受试者的结肠疾病的 方法，该方法包括：测量来自所述受试者的生物样品中选自SPB6、 FRIL、P53、1A68、ENOA、TKT、TSG6、TPM2、ADT2、FHL1、 CCR5、CEAM5、SPON2、1A68、RBX1、COR1C、VIME、PSME3、 MIC1、STK11、IPYR、SBP1、PEBP1、CATD、HPT、ANXA5、ALDOA、 LAMA2、CATZ、ACTB、AACT及其组合的至少一种生物标志物。
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附图说明
本公开的新颖特征在所附的权利要求书中特别地提出。通过参 考以下对利用本公开原理的说明性实施方案加以阐述的详细描述以 及附图，将获得对本公开的特征和优点的更好的理解，附图中：
图1A示出了显示根据实施例3A的结肠息肉生物标志物谱的预 测性能的曲线图。
图1B示出了显示根据实施例3B的结肠息肉生物标志物谱的预 测性能的曲线图，其中Y轴为平均真阳性率而X轴为假阳性率。
图2A示出了实施例3A的测试集性能的验证。
图2B示出了实施例3B的测试集性能的验证，其中Y轴为平均 真阳性率而X轴为假阳性率。
图3示出了实施例3A的特征-频率表的帕累托图(pareto plot)。
图4示出了实施例3B的特征-频率表的帕累托图，其中Y轴为 特征出现率而X轴为特征等级(feature rank)。
图5示出了显示根据实施例3A的具有较小集的结肠息肉的生 物标志物谱的预测性能的曲线图。
图6示出了实施例3A的具有较小集的测试集性能的验证。
图7示出了实施例3A中组装的分类器中表示的1014个特征的 质量，每个特征出现3次或更多次。
图8示出了实施例3B中组装的分类器中表示的206个特征的 质量。
图9提供了供包含或排除的附加生物标志物的列表。
图10示出了显示根据实施例4的CRC的生物标志物谱的预测 性能的曲线图，其中Y轴为平均真阳性率而X轴为假阳性率。
图11示出了实施例4中组装的特征-频率表的帕累托图。
图12示出了预测实施例4中组装的CRC的分类器中表示的肽 片段过渡离子。
图13显示了通用计算机系统1300的各种组件的实施方案。
图14为显示了可与本公开实施方案1400结合使用的计算机系 统架构的实施方案的示意图。
图15为显示了可与本公开实施方案1500结合使用的计算机网 络的实施方案的示意图。
图16为显示了可与本公开实施方案1600结合使用的计算机系 统架构的实施方案的示意图。
具体实施方式
I.定义
术语“结肠直肠癌状态”是指受试者的疾病状态。结肠直肠癌状 态的类型的实例包括但不限于，受试者患包括结肠直肠癌在内的癌症 的风险，疾病(例如，息肉或腺癌)的存在与否，患者的疾病阶段(例 如，癌)，和疾病治疗的疗效。
术语“质谱仪”是指测量可以转变成气相离子的质-荷(m/z)比 的参数的气相离子谱仪。质谱仪通常包括离子源和质量分析器。质谱 仪的实例为飞行时间(time-of-flight)、扇形磁场(magnetic sector)、 四极滤质器、离子阱、离子回旋共振、静电扇形分析器以及这些的混 合。“质谱法”是指使用质谱仪对气相离子的检测。
术语“串联质谱仪”是指能够进行基于m/z的离子(包括离子混 合物中的离子)鉴别或测量的两个连续阶段的任何质谱仪。该词语包 括具有两个质量分析器的质谱仪，该质量分析器能够空间串联地进行 基于m/z的离子鉴别或测量的两个连续阶段。该词语进一步包括具有 单个质量分析器的质谱仪，该质量分析器能够时间串联地进行基于 m/z的离子鉴别或测量的两个连续阶段。该词语因此明确包括Qq-TOF 质谱仪、离子阱质谱仪、离子阱-TOF质谱仪、TOF-TOF质谱仪、傅 立叶变换离子回旋共振质谱仪、静电扇形-扇形磁场质谱仪以及它们 的组合。
术语“生物芯片”是指具有附着有吸附剂的通常平坦的表面的固 体基底。通常，生物芯片的表面包含多个可寻址位置，每个可寻址位 置具有与其结合的吸附剂。生物芯片可适应于接合探针界面，并因此 起到探针的作用。蛋白质生物芯片适应于捕获多肽并且可包含在可寻 址位置附着有色谱或生物特异性吸附剂的表面。微阵列芯片通常用于 DNA和RNA基因表达检测。
术语“生物标志物”是指(具有特定的表观分子量的)多肽，与 取自对照受试者(例如，具有阴性诊断或检测不到结肠直肠癌的人， 正常或健康的受试者，或者，例如在不同时间点来自同一个体)的类 似样品相比，该多肽差异性地存在于取自患有人结肠直肠癌的受试者 的样品中。术语“生物标志物”可与术语“标志物”互换使用。生物标志 物可以是基因，如DNA或RNA或DNA或RNA的遗传变异，它们 的结合配偶体、剪接变体。生物标志物可以是蛋白质或蛋白质片段或 氨基酸序列的过渡离子，或者蛋白质氨基酸序列上的一种或多种修饰。 此外，蛋白质生物标志物可以是蛋白质或蛋白质片段或氨基酸序列的 过渡离子的结合配偶体。
术语“多肽”、“肽”和“蛋白质”在本文中可互换使用，意指氨基 酸残基的聚合物。多肽是通过相邻氨基酸残基的羧基与氨基之间的肽 键结合在一起的氨基酸的单个线性聚合物链。多肽可以例如通过加入 碳水化合物、磷酸化等来修饰。
术语“免疫测定”是使用抗体来特异性地结合抗原(例如，标志 物)的测定。免疫测定的特征在于使用特定抗体的特异性结合性质来 分离、靶向和/或量化抗原。
术语“抗体”是指基本由一个免疫球蛋白基因或多个免疫球蛋白 基因或其片段编码的、特异性结合并识别表位的多肽配体。抗体，例 如作为完整的免疫球蛋白存在或作为由各种肽酶消化产生的多个良 好表征的片段存在。这包括，例如Fab”和F(ab)”2片段。如本文所用 的，术语“抗体”还包括通过整个抗体的修饰产生的抗体片段或使用重 组DNA方法从头合成的抗体片段。它还包括多克隆抗体、单克隆抗 体、嵌合抗体、人源化抗体或单链抗体。抗体的“Fc”部分是指免疫球 蛋白重链的包含一个或多个重链恒定区结构域但不包含重链可变区 的部分。
术语“肿瘤”是指可由癌性或非癌性细胞形成的、固体或液体填 充的病变。术语“肿块”和“结节”经常与“肿瘤”同义使用。肿瘤包括恶 性肿瘤或良性肿瘤。恶性肿瘤的实例可以是已知包含转化细胞的癌。
术语“息肉”是指从粘膜凸出的组织异常生长。如果它通过狭长 的柄附接至表面，则它被称为有蒂息肉。如果不存在柄，则它被称为 无蒂息肉。息肉可以是恶性的、癌变前的或良性的。息肉可通过各种 程序如手术或者例如在结肠镜检查期间采用息肉切除术而除去。
术语“腺瘤性息肉”或“腺瘤”在本文中可互换使用，意指在结肠 内衬(lining)上生长并具有增加的癌症风险的息肉。腺瘤性息肉被 认为是恶变前的；然而，一些可能发展成结肠癌。管状腺瘤是腺瘤性 息肉中最常见的并且它们是最不可能发展成结肠癌的结肠息肉。管状 绒毛状腺瘤是另一种类型。绒毛状腺瘤是尺寸通常大于其他两种类型 的腺瘤的第三种类型，且它们在所有息肉中具有最高的发病率和死亡 率。
术语“结合配偶体”是指分子对——通常是表现出特异性结合的 生物分子对。蛋白质-蛋白质相互作用可发生在两个或更多个蛋白质 之间，当蛋白质结合在一起时，它们通常行使它们的生物功能。蛋白 质间的相互作用对大多数生物功能至关重要。例如，来自细胞外部的 信号通过信号分子的蛋白质-蛋白质相互作用，经由配体和受体蛋白 质被介导至该细胞的内部。例如，分子结合配偶体包括但不限于受体 和配体、抗体和抗原、生物素和抗生物素蛋白等。
术语“对照参考”是指已知的稳态分子或非患病健康状态，其在 其中用作相对标志物以研究波动或比较非稳态分子或正常非患病健 康状况，或者它也可以用于对值进行校准或归一化。在各个实施方案 中，对照参考值是由多个因素的组合或因素范围的组合如生物标志物 浓度的组合或浓度范围的组合计算的值。
术语“受试者”、“个体”或“患者”在本文中可互换使用，其指脊 椎动物，优选哺乳动物，更优选人。哺乳动物包括但不限于鼠类、猿、 家畜、竞技动物以及宠物。具体的哺乳动物包括大鼠、小鼠、猫、狗、 猴子和人。非人类哺乳动物包括除人之外的所有哺乳动物。在体外获 得或在体外培养的生物实体的组织、细胞及其后代也涵盖在内。
术语“体内”是指发生在受试者身体内的事件。
术语“体外”是指发生在受试者身体之外的事件。例如，体外测 定包括在受试者之外进行测定的任何测定。体外测定涵盖采用活细胞 或死细胞的基于细胞的测定。体外测定还涵盖不采用完整细胞的无细 胞测定。
术语“测量”意指包括检测样品中的标志物的存在与否、量化样 品中的标志物的量和/或定性生物标志物的类型的方法。测量可以通过 本领域中已知的方法和本文进一步描述的方法来完成，这些方法包括 但不限于质谱法和免疫测定法或可用于检测和测量本文所述的一种 或多种标志物的任何合适的方法。
术语“检测”是指鉴定待检测的物体的存在、不存在或量。非限 制性实例包括但不限于DNA分子、蛋白质、肽、蛋白质复合物、RNA 分子或代谢物的检测。
术语“差异性存在”是指在取自受试者的样品中存在的标志物与 对照参考或对照非患病健康受试者相比在量和/或频率上的差异。标志 物可以在量、频率或这两个方面差异性存在。
术语“监测”是指记录连续变化参数的改变。
术语“诊断的”或“诊断”在本文中可互换使用，意指鉴定病理状 况的存在或性质，或病理状况的亚型，即结肠息肉的存在或风险。诊 断方法在它们的灵敏度和特异性上不同。诊断方法可不提供状况的确 诊；然而，如果该方法提供了有助于诊断的正向指示，那就足够了。
术语“预后”在本文中用来指疾病或疾病进展(包括复发和治疗 反应)的可能性的预测。
术语“预测”在本文中用来指患者将具有特定临床结果(无论是 阳性还是阴性)的可能性。本公开的预测方法可以在临床上用来通过 为任何特定患者选择最合适的治疗方式来作出治疗决定。
术语“报告”是指由本公开的方法提供给医师的不确定的或必要 时为确定的打印结果。该报告可指示病理状况的存在、性质或风险。 该报告还可指示什么样的治疗是最合适的；例如，不处理、手术、进 一步测试或施用治疗剂。
II.总体概述
用于诊断疾病、疾病预后和预测对疾病的药物反应的生物标志 物谱的开发对于医学界可能是有用的。
本公开提供了通过使用各种测定外加由受计算机可读介质指示 的处理器执行的算法以确定生物标志物来分析来自个体的复杂生物 样品的方法、组合物、系统和试剂盒，该生物标志物指示临床状态或 健康的恶化或改善。通常，该方法使用来自生物系统的多个分子生物 学水平(例如，多核苷酸(DNA或RNA)、多肽和代谢物水平)的 多种分子来鉴定疾病如结肠癌、结肠息肉和预期的各种结肠直肠疾病 的生物标志物或生物标志物谱。
本公开还提供了可用于诊断、预测、预后或监测个体的结肠息 肉或结肠癌的存在或从其恢复的生物标志物和系统。
本公开还提供了商业化诊断试剂盒，其通常将包括用于检测本 文所提供的生物标志物的组合物、说明以及指示个体的结肠息肉或结 肠癌的诊断、预测、预后、存在或从其恢复的报告。由该报告提供的 临床预测或状态可指示，例如，尚未在临床上表现出结肠息肉或癌的 个体在某一时间段内或者在给定年龄下，受试者将患有临床上表现的 结肠息肉和结肠癌的可能性、几率或风险。
III.方法
本公开提供了使用通过质谱法获得的数据，基于蛋白质组和/ 或基因组模式的医学诊断方法。该方法允许基于患者的蛋白质组和/ 或基因组模式按照患者的疾病阶段对患者进行分类。
结肠直肠癌，也被称为结肠癌、直肠癌或肠癌，是由结肠或直 肠中的不受控的细胞生长而导致的癌症。此外，本公开提供了用于结 肠息肉和结肠直肠癌的医学诊断的新的生物标志物。
结肠息肉为在大肠或结肠的内衬上形成的细胞良性块。几乎所 有的息肉最初都是非恶性的。然而，随着时间的推移，一些可能变成 癌性病变。大部分结肠息肉的原因是未知的，但它们常见于成人中。 由于结肠息肉是无症状的，因此建议定期筛查结肠息肉。当前，用于 筛查息肉的方法是高度侵入性的且昂贵的。因此，尽管结肠镜检查筛 查在预防和减少结肠癌方面存在益处，但被建议该程序的许多人拒绝 进行此筛查，主要是因为担心成本、不适和不良事件。这类人仅在美 国就有数千万人。
有助于对患者具有存在结肠息肉、腺瘤或癌性肿瘤如癌的较高 风险的可能性进行分类的分子测试可帮助医师指导患者关于抗拒进 行结肠镜检查的态度和行为。增加的结肠镜检查筛查依从性将导致早 期检测出癌症或癌变前腺瘤，并减少与结肠癌相关的发病率和死亡率。
本公开提供了侵入性低于结肠镜检查并且将确定个体的蛋白质 表达指纹或谱的蛋白质生物标志物测试。在本公开的一些应用中，基 于所预测的个体的息肉状态和/或患有结肠息肉或结肠癌的风险的可 能性而生成报告。因此，本公开提供了提供关于个体的结肠息肉状态 和/或患有结肠息肉或结肠癌的风险的信息的方法、试剂盒、组合物和 系统。
在本公开的一个方面，已通过基于LCMS的程序鉴定出一组基 于蛋白质的分类器(例如，生物标志物谱)，该程序能够预测关于患 者的结肠息肉、腺瘤或癌的存在与否的结肠镜检查程序结果。
在本公开的一个方面，已使用基于LCMS的方法来鉴定基于血 浆-蛋白质的分子特征，该分子特征可包含鉴别更可能患有息肉、腺 瘤或肿瘤的患者的一个或多个分类器。
在本公开的一个方面，分类器用于确定哪些个体不可能患有息 肉、腺瘤或肿瘤，并因此可能无需进行结肠镜检查。
在本公开的一个方面，分类器用于通过比较程序之前与之后的 分类器值来测量结肠镜检查期间疑似息肉去除的完成度。
在本公开的一个方面，在定期筛查结肠镜检查之间的间隔期间 使用分类器来捕捉所谓的间期疾病(interval disease)。
在本公开的一个方面，分类器用于增加具有升高的风险谱的患 者的连续结肠镜检查之间的时间。具有升高的风险谱的患者的实例可 包括先前进行过息肉切除术或其他病理操作的患者。
本公开提供了在从完整蛋白质衍生的特定片段的大小和序列以 及沿全蛋白质多肽链发生酶切(例如，胰蛋白酶消化等)的位置(其 为结肠的病变状态的特征)方面生成和分析血液蛋白质片段谱的方法。
预期本公开提供的方法、试剂盒、组合物和系统还可根据应用 全部或部分自动化。
A.基于算法的方法
本公开提供了用于预测结肠息肉或结肠癌患者的临床结果的基 于算法的诊断测定。可单独使用一种或多种蛋白质生物标志物的表达 水平或将其设置成功能子集来计算可用于预测临床结果的可能性的 定量得分。
本公开的“生物标志物”或“标志物”可以是具有特定表观分子量 的多肽，基因如DNA或RNA或DNA或RNA的遗传变异，它们的 结合配偶体，剪接变体。生物标志物可以是蛋白质或蛋白质片段或氨 基酸序列的过渡离子，或者蛋白质氨基酸序列上的一个或多个修饰。此外，蛋白质生物标志物可以是蛋白质或蛋白质片段或氨基酸序列的 过渡离子的结合配偶体。
通过实施本公开方法提供的基于算法的测定和相关信息促进了 对表现出结肠肿瘤的患者的最佳治疗决策制定。例如，这样的临床工 具将使医师能够鉴定具有患息肉或癌的低可能性并因此无需抗癌治 疗的患者，或具有患侵袭性癌症的高可能性并因此将需要抗癌治疗的 患者。
可通过应用特定算法来确定定量得分。在本文公开的方法中用 于计算定量得分的算法可对一种生物标志物或成组生物标志物的表 达水平值进行分组。此外，特定一组生物标志物的形成可促进生物标 志物或生物标志物子集(例如分类器)的各个表达水平对定量得分的 贡献的数学权重。本公开提供了用于计算定量得分的各种算法。
B.数据的归一化
在本文公开的方法中使用的表达数据可进行归一化。归一化是 指对例如所测定的基因的量或蛋白质水平的差异以及所用模板的质 量的可变性进行校正，以除去在处理和检测基因或蛋白质表达中涉及 的不期望的系统变异测量来源的过程。其他的系统变异来源可归因于 实验室处理条件。
在一些情况下，归一化方法可用于实验室处理条件的归一化。 可与本公开的方法一起使用的实验室处理的归一化的非限制性实例 包括但不限于：解释在数据生成过程中使用的仪器、试剂和设备之间 的系统性差异，和/或在数据采集中的日期和时间或时间消逝。
测定可通过并入某些归一化的标准基因或蛋白质的表达来提供 归一化，这些归一化的标准基因或蛋白质在相关条件下在表达水平上 无显著不同，也就是说，在该特定样品类型中，它们已知具有稳定且 一致的表达水平。可在本公开中使用的合适的归一化基因和蛋白质包 括持家基因。(参见，例如E.Eisenberg等人,Trends in Genetics 19(7):362-365(2003))。在一些应用中，归一化的生物标志物(基因 和蛋白质)，也被称为参考基因，已知与无结肠息肉的患者相比，不 表现出结肠息肉或癌症的在意义上不同的表达水平。在一些应用中， 添加可被使用并代表具有已知性质的实体的稳定同位素标记的标准 物以用于数据归一化可能是有用的。在其他应用中，标准的固定化样 品可与每个分析批次一起进行测量，以解释仪器和日常测量的可变性。
在一些应用中，诊断、预后和预测基因可相对于至少2、3、4、 5、6、7、8、9、10、15、20、25、30、40或50个或更多个参考基因 和蛋白质的平均值进行归一化。归一化可基于所有测定的生物标志物 的信号平均值或中值或通过整体生物标志物归一化方法来进行。本领域技术人员将认识到，可以采用许多种方式来实现归一化，并且上述 技术仅旨在示例。
C.数据的标准化
在本文公开的方法中使用的表达数据可以被标准化。标准化是 指有效地将所有基因置于可比标度上的过程。因一些基因将比其他基 因表现出更多的变异(更广范围的表达)而进行该过程。标准化通过 将每个表达值除以其在该基因或蛋白质的所有样品中的标准差来进 行。
D.临床结果得分
用于亚选择鉴别性生物标志物和用于构建分类模型的机器学习 算法的使用可用于确定临床结果得分。这些算法包括但不限于，弹性 网络、随机森林、支持向量机和逻辑回归。这些算法可对重要的生物 标志物特征进行磨砺(hone in)并将基础测量值转换成与例如临床结 果、疾病风险、治疗反应和/或疾病状态的分类相关的得分或概率。
在一些应用中，定量得分的增加指示不良临床结果、良好临床 结果、疾病的高风险、疾病的低风险、完全反应、部分反应、病情稳 定、无反应和为疾病管理推荐的治疗的可能性的增加。在一些应用中， 定量得分的降低指示不良临床结果、良好临床结果、疾病的高风险、 疾病的低风险、完全反应、部分反应、病情稳定、无反应和为疾病管 理推荐的治疗的可能性的增加。
在一些应用中，来自患者的与参考谱类似的生物标志物谱指示 不良临床结果、良好临床结果、疾病的高风险、疾病的低风险、完全 反应、部分反应、病情稳定、无反应和为疾病管理推荐的治疗的可能 性的增加。在一些应用中，来自患者的与参考谱不同的生物标志物谱 表明不良临床结果、良好临床结果、疾病的高风险、疾病的低风险、 完全反应、部分反应、病情稳定、无反应和为疾病管理推荐的治疗的 可能性的增加。
在一些应用中，一个或多个生物标志物阈值的增加指示不良临 床结果、良好临床结果、疾病的高风险、疾病的低风险、完全反应、 部分反应、病情稳定、无反应和为疾病管理推荐的治疗的可能性的增 加。在一些应用中，一个或多个生物标志物阈值的降低指示不良临床 结果、良好临床结果、疾病的高风险、疾病的低风险、完全反应、部 分反应、病情稳定、无反应和为疾病管理推荐的治疗的可能性的增加。
在一些应用中，定量得分、一个或多个生物标志物阈值、类似 的生物标志物谱值或其组合的增加指示不良临床结果、良好临床结果、 疾病的高风险、疾病的低风险、完全反应、部分反应、病情稳定、无 反应和为疾病管理推荐的治疗的可能性的增加。在一些应用中，定量 得分、一个或多个生物标志物阈值、类似的生物标志物谱值或其组合 的降低指示不良临床结果、良好临床结果、疾病的高风险、疾病的低 风险、完全反应、部分反应、病情稳定、无反应和为疾病管理推荐的 治疗的可能性的增加。
E.样品制备和处理
在分析样品之前，可能期望对样品进行一个或多个样品制备操 作。通常，这些样品制备操作可包括，如从细胞或组织提取和分离细 胞内物质等操作，例如，从样品提取核酸、蛋白质或其他大分子。
可与本公开的方法一起使用的样品制备包括但不限于，离心、 亲和色谱法、磁分离、免疫测定、核酸分析、基于受体的测定、细胞 计数测定、比色测定、酶测定、电泳分析、电化学测定、光谱测定、 色谱测定、显微检测、地形分析(topographic assay)、量热分析、放射性同位素测定、蛋白质合成分析、组织学测定、培养试验以及它们 的组合。
样品制备可进一步包括用合适的溶剂和量进行稀释，以确保适 当的浓度水平范围通过给定的测定法能检测到。
从样品的细胞内空间接近核酸和大分子通常可通过物理、化学 方法或二者的组合来进行。在该方法的一些应用中，在分离粗提取物 后，通常期望分离核酸、蛋白质、细胞膜颗粒等。在该方法的一些应 用中，期望将核酸与其蛋白质和细胞膜颗粒保持在一起。
在本文提供的方法的一些应用中，可在使用本公开的方法进行 分析之前，从生物样品中提取核酸和蛋白质。提取可通过包括但不限 于使用去污剂裂解物、超声处理或采用玻璃珠涡旋的手段进行。
在一些应用中，分子可以使用本领域中适合的任何技术进行分 离，该技术包括但不限于，使用梯度离心(例如，氯化铯梯度、蔗糖 梯度、葡萄糖梯度等)、离心方案、沸腾、纯化试剂盒以及使用采用 试剂提取方法(如使用Trizol或DNAzol的方法)的液体提取的技术。
可根据期望的检测方法，基于标准生物样品制备法制备样品。 例如对于质谱法检测，可以对从患者获得的生物样品进行离心、过滤、 通过免疫亲和柱的处理、分离成级分、部分消化以及它们的组合。各 种级分可再悬浮于适当的载体中，如缓冲液或用于检测和分析的其他 类型的上样溶液，包括LCMS上样缓冲液。
F.检测方法
本公开提供了用于检测生物样品中的生物标志物的方法。生物 标志物可包括但不限于，蛋白质、代谢物、DNA分子和RNA分子。 更具体地，本公开基于在患有结肠息肉或可能发展结肠息肉的受试者 中差异性表达的蛋白质生物标志物的发现。因此，生物样品中这些差 异性表达的生物标志物中的一种或多种的检测提供了关于受试者是 否处于结肠息肉的风险下或患有结肠息肉以及该状况的性质或状态 的类型的有用信息。任何合适的方法可用于检测本文所述的一种或多 种生物标志物。
可在本公开中使用的有用的分析物捕获剂包括但不限于，抗体， 如含有抗体的粗血清、纯化的抗体、单克隆抗体、多克隆抗体、合成 抗体、抗体片段(例如，Fab片段)；抗体相互作用剂，如蛋白A、 碳水化合物结合蛋白质和其他相互作用物；蛋白质相互作用物(例如，抗生物素蛋白及其衍生物)；肽；以及小化学实体，如酶底物、辅因 子、金属离子/螯合物和半抗原。可对抗体进行修饰或化学处理，以优 化与靶标或固体表面(例如，生物芯片和柱)的结合。
在本公开的一个方面，可以使用免疫测定在生物样品中检测生 物标志物。免疫测定是使用特异性结合至或识别抗原(例如，蛋白质 或肽上的位点，即生物标志物靶标)的抗体的测定。该方法包括以下 步骤：使生物样品与抗体接触，并使该抗体与样品中的抗原形成复合 物，洗涤该样品并用检测试剂检测抗体-抗原复合物。在一个实施方 案中，识别生物标志物的抗体可以是市售的。在另一个实施方案中， 识别生物标志物的抗体可以通过已知的抗体产生方法生成。
或者，可以使用间接测定法检测样品中的标志物，其中，例如 使用标记的第二抗体来检测结合的标志物-特异性抗体。示例性的可 检测标记物包括磁珠(例如，DYNABEADSTM)、荧光染料、放射性 标记物、酶(例如，辣根过氧化物、碱性磷酸酶以及其他常用的酶) 和量热标记物，如胶体金或有色玻璃或塑料珠。可以使用竞争或抑制 试验和/或在竞争或抑制试验中检测样品中的标志物，其中，例如，与 标志物的不同表位结合的单克隆抗体与该混合物同时孵育。
使用免疫测定检测抗原的条件将取决于所用的特定抗体。而且， 孵育时间将取决于测定形式、标志物、溶液体积、浓度等。尽管根据 所用的抗体，免疫测定可以在诸如10摄氏度到40摄氏度的温度范围 进行，但通常免疫测定将在室温下进行。
存在本领域中已知的多种类型的免疫测定，其作为起始基础可 用于对该测定进行调整以用于检测本公开的生物标志物。有用的测定 可包括，例如，酶免疫测定(EIA)，诸如酶联免疫吸附测定(ELISA)。 存在这些方法的许多变化形式，但这些变化形式都是基于类似的理念。 例如，如果抗原可与固体支持物或表面结合，则它可通过使其与特异 性抗体反应进行检测，并且该抗体可通过使其与第二抗体反应或者通 过将标记物直接引入第一抗体来进行定量。或者，抗体可与固体表面 和添加的抗原结合。随后，可添加并检测识别抗原上的不同表位的第 二抗体。这通常称为“夹心法测定(sandwich assay)”并通常可用于避 免高背景或非特异性反应的问题。这些类型的测定具有足以测定生物 样品中低浓度的抗原的灵敏性和重现性。
免疫测定可用于确定样品中标志物的存在与否以及样品中的标 志物的量。用于测量抗体-标志物复合物的量或存在的方法包括但不 限于，荧光法、发光法、化学发光法、吸光度法、反射率法、透射率 法、双折射法或折射率法(例如，表面等离子体共振、椭圆测量法、 共振镜法、光栅耦合器波导法或干涉法)。通常，这些试剂与光学检 测方法如各种形式的显微术、成像方法和非成像方法一起使用。电化 学方法包括伏安法和安培法。射频法包括多极共振光谱法。
在一个方面，本公开可使用抗体来检测生物标志物。可以使抗 体与该测定的生物标志物特异性结合，这样的抗体可使用本领域中已 知的标准方法来制备。例如，多克隆抗体可通过将抗原注射至诸如小 鼠、大鼠、兔、山羊、绵羊或马等哺乳动物来产生，以用于产生大量 抗体。从这些动物中分离的血液含有多克隆抗体——与相同抗原结合 的多种抗体。或者，多克隆抗体可以通过将抗原注射至鸡以便在蛋黄 中产生多克隆抗体来产生。此外，可以使抗体特异性识别生物标志物 的修饰形式，如生物标志物的磷酸化形式，也就是说，它们将识别磷 酸化后的酪氨酸或丝氨酸，但在不存在磷酸的情况下不识别。这样， 抗体可用于确定特定生物标志物的磷酸化状态。
抗体可商购获得或使用已确立的方法产生。为了获得对抗原的 单个表位具有特异性的抗体，从动物中分离分泌抗体的淋巴细胞并通 过将它们与癌细胞系融合而永生化。该融合的细胞被称为杂交瘤，并 将在培养中持续生长并分泌抗体。单个杂交瘤细胞通过稀释克隆以生 成均产生相同抗体的细胞克隆来分离；这些抗体被称为单克隆抗体。
多克隆和单克隆抗体可以采用若干种方式进行纯化。例如，可 以使用抗原亲和色谱法分离抗体，该抗原亲和色谱法与细菌蛋白质如 蛋白A、蛋白G、蛋白L或重组融合蛋白、蛋白A/G偶联，随后通过 280nm处的紫外线吸光度来检测洗脱物级分，以确定哪些级分含有所 述抗体。蛋白A/G与人IgG的所有亚类结合，从而使它对于纯化其亚 类尚未确定的多克隆或单克隆IgG抗体是有用的。另外，它与IgA、 IgE、IgM和(在较小程度上)IgD结合。蛋白A/G还与小鼠IgG的 所有亚类结合但不结合小鼠IgA、IgM或血清白蛋白。这一特征使得 蛋白A/G用于纯化和检测小鼠单克隆IgG抗体，而不受IgA、IgM和 血清白蛋白的干扰。
抗体可来源于分子的不同类别或同种型，如IgA、IgA IgD、IgE、IgM和IgG。将IgA设计成用于在体液中分泌，而将其他抗体如IgM 设计成在细胞表面上表达。在生物研究中最有用的抗体是IgG类 别——被制备并分泌并可识别特异性抗原的蛋白质分子。IgG包含两个亚基，包括两个“重”链和两个“轻”链。它们组装成对称结构且每个 IgG具有两个相同的抗原识别域。该抗原识别域为来自重链和轻链的 氨基酸的组合。该分子的形状大致类似于“Y”，且该分子的臂/尖端包 含抗原识别区或Fab(片段，抗原结合)区，而Fc(片段，可结晶)区的茎不参与识别并且相当恒定。恒定区在相同同种型的所有抗体中 相同，但在不同同种型的抗体中不同。
也可以在通过Western印迹法分级分离之后，使用抗体来检测 蛋白质。在一个方面，本公开可使用Western印迹法来检测生物标志 物。Western印迹法(蛋白质免疫印迹)是用于检测给定样品或来自 样品的蛋白质提取物中的特异性蛋白质的分析技术。它使用凝胶电泳 (SDS-PAGE)根据蛋白质的三维结构来分离任一天然蛋白质，或者 它可在变性条件下运行以根据蛋白质长度来分离蛋白质。通过凝胶电 泳分离后，随后将蛋白质转移到膜(通常为硝酸纤维素或PVDF)上。 然后，可将从SDS-PAGE转移到膜上的蛋白质与特定抗体在轻柔搅拌 下一起孵育，漂洗以除去非特异性结合物，并且与印迹结合的蛋白质 -抗体复合物可使用一步或两步检测法进行检测。一步法包括既识别 感兴趣的蛋白质又包含可检测标记物的探针抗体，探针通常对已知的 蛋白质标签是可用的。两步检测法包含具有报道酶或与其结合的报道 分子的第二抗体。采用适当的参考对照，这种方法可用于测量蛋白质的丰度。
在一个方面，本公开的方法可使用流式细胞术。流式细胞术是 可用于生物标志物的检测、定量(细胞计数)和细胞分离的基于激光 的生物物理技术。该技术常规用于健康病症，尤其是血癌的诊断。在 通常情况下，流式细胞术通过下列步骤工作：将单细胞悬浮在液体流 中，将单波长光束(通常为激光)导向至液体流上，并由电子检测装 置检测由穿过细胞而引起的散射光。荧光激活细胞分选(FACS)是 专业型的流式细胞术，其通常借助于荧光标记的抗体来检测细胞上感 兴趣的抗原。这一在FACS中使用抗体标记的附加特征提供了基于特 定的光散射和每个细胞的荧光特性对荧光标记的细胞的同时多参数 分析和定量，并且它提供了感兴趣的细胞群体的物理分离以及传统流 式细胞术所实现的那些。
很多种荧光团可用作流式细胞术中的标记物。荧光团通常附接 至识别细胞之上或之内的靶特征的抗体。合适的荧光标记物的实例包 括但不限于：荧光素(FITC)，5,6-羧甲基荧光素，德克萨斯红(Texas red)，硝基苯-2-氧杂-1,3-二唑-4-基(NBD)，以及花青染料Cy3、 CY3.5、Cy5、Cy5.5和Cy7。其他荧光标记物如Alexa染料、 DNA内容物染料如DAPI、Hoechst染料是本领域中公知的，并且均 可从多个商业来源容易地获得。每个荧光团具有特征峰激发和发射波 长，并且发射光谱通常重叠。这些荧光标记物的吸收和发射最大值分 别为：FITC(490nm；520nm)、Cy3(554nm；568nm)、Cy3.5(581nm； 588nm)、Cy5(652nm；672nm)、Cy5.5(682nm；703nm)和Cy7(755 nm；778nm)，因此选择不具有很多光谱重叠的荧光标记物允许它们 的同时检测。荧光标记物可以从多个商业来源获得。可区分的荧光标 记物的最大数目被认为是约17或18种不同的荧光标记物。这个水平 的复杂读出需要进行费时费力的优化以限制伪迹，以及进行复杂的反 卷积算法以分离重叠的光谱。量子点因其较窄的发射峰而有时用来代 替传统的荧光团。可用于检测的其他方法包括同位素(如镧系元素的 同位素)标记的抗体。然而，该技术最终破坏细胞，从而阻止对其回 收用于进一步的分析。
在一个方面，本公开的方法可以使用免疫组织化学法来检测本 公开的生物标志物的表达水平。因此，使用对每个标志物具有特异性 的抗体来检测组织样品中所请求保护的生物标志物的表达。该抗体可 通过抗体本身的直接标记，例如用放射性标记物、荧光标记物、半抗 原标记物如生物素或酶(如辣根过氧化物酶或碱性磷酸酶)标记来检 测。或者，将未标记的第一抗体与标记的第二抗体结合使用，该第二 抗体包含对第一抗体具有特异性的抗血清、多克隆抗血清或单克隆抗 体。免疫组织化学方案是本领域公知的，并且方案和抗体可商购获得。 或者，可制备针对如本文公开的生物标志物或生物标志物的修饰形式或结合配偶体的抗体，其对于确定组织样品中的表达水平将是有用的。
在一个方面，本公开的方法可使用生物芯片。生物芯片可用于 筛选大量大分子。在该技术中，大分子以有序的阵列形式附着到生物 芯片的表面。测试区的网格图案允许由成像软件进行分析，以快速且 同时量化在分析物的预定位置(地址)处的单个分析物。CCD相机是 能够准确地检测并量化芯片上的非常低水平的光的灵敏且高分辨率 的传感器。
生物芯片可采用固定的核酸分子、全长蛋白质、抗体、亲和体 (affibodies)(被工程化为模拟单克隆抗体的小分子)、适体(基于 核酸的配体)或化学化合物进行设计。芯片可被设计用于在一个芯片 上检测多种大分子类型。例如，芯片可被设计用于在一个芯片上检测 核酸分子、蛋白质和代谢物。生物芯片用于并被设计成同时分析单个 样品中的一组生物标志物，从而产生这些生物标志物的受试者谱。生 物芯片的使用允许进行多个分析，从而减少了总处理时间和所需样品 的量。
蛋白质微阵列是可在本公开中使用的特定类型的生物芯片。该 芯片包含支持表面如载玻片、硝酸纤维素膜、珠子或微量滴定板，捕 获蛋白质阵列以阵列的形式结合到固体表面上。蛋白质阵列检测方法 必须提供高信号和低背景。将通常用荧光染料标记的检测探针分子添 加至阵列。探针与固定的蛋白质之间的任何反应发射出可由激光扫描 仪读取的荧光信号。此类蛋白质微阵列是快速、自动化的，并为诊断 试验提供高灵敏度的蛋白质生物标志物读出。然而，本领域技术人员 将立即理解它们是可与该技术一起使用的多种检测方法。
存在至少三种类型的当前用于研究蛋白质的生物化学活性的蛋 白质微阵列。例如，存在分析微阵列(也称为捕获阵列)、功能性蛋 白质微阵列(也称为靶蛋白质阵列)和反相蛋白质微阵列(RPA)。
本公开提供了使用分析型蛋白质微阵列对生物标志物的检测。 分析型蛋白质微阵列使用抗体、适体或亲和体的文库来构建。该阵列 用复杂蛋白质溶液如血液、血清或细胞裂解物进行探查，该复杂蛋白 质溶液通过捕获与其特异性结合的蛋白质分子而起作用。使用各种检 测系统对所产生的结合反应的分析可提供关于样品中的特定蛋白质 的表达水平以及结合亲和性和特异性的测量的信息。这种类型的蛋白 质微阵列在比较不同样品中的蛋白质表达方面是特别有用的。
在一个方面，本公开的方法可以使用功能性蛋白质微阵列，该 功能性蛋白质微阵列通过固定大量的纯化的全长功能性蛋白质或蛋 白质结构域而构建，并用于鉴定蛋白质-蛋白质、蛋白质-DNA、蛋白 质-RNA、蛋白质-磷脂和蛋白质-小分子相互作用，以测定酶活性以及 检测抗体并证明抗体的特异性。这些蛋白质微阵列生物芯片可用于研 究样品中的整个蛋白质组的生化活性。
在一个方面，本公开的方法可使用反相蛋白质微阵列(RPA)。 反相蛋白质微阵列由排列到该微阵列上的组织和细胞裂解物构建，并 用针对感兴趣的靶蛋白质的抗体来探查。这些抗体通常用化学发光、 荧光或比色测定法进行检测。除了裂解物中的蛋白质外，也将参考对 照肽打印在载玻片上，以允许蛋白质定量。RPA允许确定改变的蛋白 质或可能是疾病的结果并存在于病变细胞中的其他物质的存在。
本公开提供了使用质谱分析法(或者称为质谱法)对生物标志 物的检测。质谱法(MS)是测量带电粒子的质荷比的分析技术。它 主要用于确定样品或分子的元素组成，并用于解释分子如肽和其他化 学化合物的化学结构。MS通过电离化学化合物以产生带电分子或分 子片段并测量它们的质荷比而工作。MS仪器通常由以下三个模块组 成：(1)离子源，其可将气相样品分子转化为离子(或者，在电喷 雾电离的情况下，使溶液中存在的离子移动至气相中)；(2)质量 分析器，其通过施加电磁场根据离子的质量对其进行分选；以及(3)检测器，其测量指标量(indicator quantity)的值并由此提供数据以供 计算存在的每个离子的丰度。
将在本公开中使用的合适的质谱方法包括但不限于以下方法中 的一种或多种：电喷雾电离质谱法(ESI-MS)、ESI-MS/MS、 ESI-MS/(MS)n、基质辅助激光解吸电离飞行时间质谱法 (MALDI-TOF-MS)、表面增强激光解吸/电离飞行时间质谱法 (SELDI-TOF-MS)、串联液相色谱-质谱(LC-MS/MS)质谱法、硅 上解吸/电离(DIOS)、二次离子质谱法(SIMS)、四极杆飞行时间 (Q-TOF)、大气压化学电离质谱法(APCI-MS)、APCI-MS/MS、 APCI-(MS)、大气压光电离质谱法(APPI-MS)、APPI-MS/MS和 APPI-(MS)n、四极杆质谱法、傅立叶变换质谱法(FTMS)和离子阱 质谱法，其中n是大于零的整数。
为了深入了解样品的基础蛋白质组，通常使用LC-MS来解析复 杂混合物的组分。LC-MS方法通常包括蛋白酶消化和变性(通常涉及 蛋白酶如胰蛋白酶，和变性剂，如用于使三级结构变性的尿素和用于 为半胱氨酸残基加帽的碘乙酰胺)，随后进行具有肽质量指纹分析的 LC-MS或LC-MS/MS(串联MS)以获得单个肽的序列。LC-MS/MS 最常用于复杂样品的蛋白质组分析，其中即使采用高分辨率质谱仪， 肽质量仍可能重叠。复杂生物流体如人血清的样品可首先在 SDS-PAGE凝胶或HPLC-SCX上分离并随后在LC-MS/MS中运行， 以允许鉴定超过1000种蛋白质。
尽管多种质谱方法可与本文所提供的方法一起使用，但在一些 应用中，可能期望量化生物样品中来自所选的感兴趣的蛋白质子集中 的蛋白质。可在本公开中使用的一种这样的MS技术是多重反应监测 质谱法(MRM-MS)，或者可替代地被称为选择反应监测质谱法 (SRM-MS)。
MRM-MS技术使用三重四极杆(QQQ，triple quadrupole)质谱 仪来从感兴趣的肽中选择带正电荷的离子，使带正电荷的离子片段化， 并随后测量所选带正电荷的片段离子的丰度。这种测量方法通常被称 为过渡法(transition)。例如，从该方法得到的过渡离子参见表1。
在一些应用中，MRM-MS与高压液相色谱法(HPLC)和最近 的超高压液相色谱法(UHPLC)耦合。在其他应用中，MRM-MS与 采用QQQ质谱仪的UHPLC耦合，以对所有感兴趣的肽和蛋白质进 行所需的LC-MS过渡测量。
在一些应用中，可使用四极杆飞行时间(qTOF)质谱仪、飞行 时间-飞行时间(TOF-TOF)质谱仪、轨道阱质谱仪、四极杆轨道阱 质谱仪或任何四极杆离子阱质谱仪从一种或多种感兴趣的肽中选择 带正电荷的离子。然后，可测量片段化的带正电荷的离子来确定带正电荷的离子的丰度以用于量化感兴趣的肽或蛋白质。
在一些应用中，可使用飞行时间(TOF)、四极杆飞行时间(qTOF) 质谱仪、飞行时间-飞行时间(TOF-TOF)质谱仪、轨道阱质谱仪或 四极杆轨道阱质谱仪来测量来自未片段化的感兴趣的蛋白质的带正 电荷的肽离子的质量和丰度，以供定量。在本申请中，分析物质量测 量的准确度可用作测定的选择标准。具有已知组成和浓度的同位素标 记的内标物可用作质谱定量方法的一部分。
在一些应用中，可使用飞行时间(TOF)、四极杆飞行时间(qTOF) 质谱仪、飞行时间-飞行时间(TOF-TOF)质谱仪、轨道阱质谱仪或 四极杆轨道阱质谱仪来测量感兴趣的蛋白质的质量和丰度以供定量。 在本申请中，分析物质量测量的准确度可用作测定的选择标准。任选 地，本申请在通过质谱法分析之前，可使用蛋白质的蛋白水解消化。 具有已知组成和浓度的同位素标记的内标物可用作质谱定量方法的 一部分。
在一些应用中，各种电离技术可与本文提供的质谱仪耦合，以 产生所需的信息。可与本公开一起使用的非限制性的示例性电离技术 包括但不限于：基质辅助激光解吸电离(MALDI)、解吸电喷雾电离 (DESI)、直接辅助实时(DART)、表面辅助激光解吸电离(SALDI) 或电喷雾电离(ESI)。
在一些应用中，HPLC和UHPLC可与质谱仪耦合。在质谱分析 前，可进行多种其他肽和蛋白质分离技术。可用于从基质背景中分离 所需分析物(例如，肽或蛋白质)的一些示例性分离技术包括但不限 于，蛋白质或肽的反相液相色谱法(RP-LC)、MALDI前的离线液 相色谱法(LC)、一维凝胶分离、二维凝胶分离、强阳离子交换(SCX) 色谱法、强阴离子交换(SAX)色谱法、弱阳离子交换(WCX)和弱 阴离子交换(WAX)。在质谱分析前可使用上述技术中的一种或多 种。
在本公开的一个方面，可使用微阵列检测生物样品中的生物标 志物。还可以使用微阵列技术鉴定或确认差异性基因表达。因此，可 使用微阵列技术测量新鲜或固定的组织中的表达谱生物标志物。在该 方法中，将感兴趣的多核苷酸序列(包括cDNA和寡核苷酸)铺在或 排列在微芯片基底上。随后，将排列的序列与来自感兴趣的细胞或组 织的特异性DNA探针杂交。mRNA的来源通常是从生物样品中分离 的总RNA，并且可使用相应的正常组织或细胞系来确定差异性表达。
在微阵列技术的具体实施方案中，将PCR扩增的cDNA克隆插 入物以密集阵列形式施加至基底。优选将至少10,000个核苷酸序列施 加至基底。以每个基底10,000个元件固定在微芯片上的微阵列基因适 于严格条件下的杂交。荧光标记的cDNA探针可通过经由从感兴趣组 织中提取的RNA的逆转录掺入荧光核苷酸而产生。施加至芯片的标 记的cDNA探针与阵列上的每个DNA位点特异性地杂交。严格洗涤 以除去非特异性结合的探针后，通过诸如共聚焦激光显微镜的设备或 通过诸如CCD相机的另一种检测方法来扫描微阵列芯片。对每个排 列的元件的杂交的定量允许评估相应的mRNA丰度。通过采用双色 荧光，从两个RNA来源产生的分别标记的cDNA探针与阵列成对杂 交。来自两个来源的与每个指定基因相对应的转录物的相对丰度因此 同时得以确定。微阵列分析可通过市售设备按照生产商的方案来进行。
在本公开的一个方面，生物标志物可使用qRT-PCR在生物样品 中进行检测，该生物标志物可用于比较在进行或不进行药物治疗下正 常和肿瘤组织中的不同样品群体的mRNA水平，以表征基因表达模 式，区分密切相关的mRNA，并分析RNA结构。通过RT-PCR进行基因表达谱分析的第一步是从生物样品中提取RNA，接着将RNA模 板逆转录成cDNA，并通过PCR反应进行扩增。逆转录反应步骤通常 使用特异性引物、随机六聚体或寡-dT引物根据表达谱分析的目标来 引发。两种常用的逆转录酶是禽(avilo)成髓细胞瘤病毒逆转录酶(AMV-RT)和莫洛尼(Moloney)鼠白血病病毒逆转录酶(MLV-RT)。
尽管PCR步骤可使用多种热稳定的DNA依赖性DNA聚合酶， 但它通常采用Taq DNA聚合酶，Taq DNA聚合酶具有5'-3'核酸酶活 性但缺乏3'-5'校正核酸内切酶活性。因此，TaqManTM PCR通常使用 Taq或Tth聚合酶的5'-核酸酶活性来水解与其靶扩增子结合的杂交探 针，但具有等效的5'核酸酶活性的任何酶均可以使用。使用两个寡核 苷酸引物产生PCR反应的典型扩增子。第三寡核苷酸或探针被设计 用于检测位于两个PCR引物之间的核苷酸序列。探针不可由Taq DNA 聚合酶延伸，并采用报道荧光染料和猝灭荧光染料进行标记。当报道 染料和猝灭染料在探针上位置靠近时，来自报道染料的任何激光诱导 的发射被猝灭染料猝灭。在扩增反应过程中，Taq DNA聚合酶以模板 依赖性方式裂解探针。所得探针片段在溶液中解离，并且来自释放的 报道染料的信号不受第二荧光团的猝灭效应的影响。释放报道染料的 一个分子用于每个新合成的分子，并且非猝灭的报道染料的检测提供 了数据的定量解释的基础。
TaqManTM RT-PCR可使用市售的设备如ABI PRISM 7700TM Sequence DetectionSystemTM(Perkin-Elmer-Applied Biosystems,Foster City,Calif.,USA)或LightCycler(Roche Molecular Biochemicals, Mannheim,德国)进行。在一个优选的实施方案中，5'核酸酶程序在 实时定量PCR设备如ABI PRISM 7700TM Sequence Detection SystemTM上运行。该系统包含热循环仪、激光器、电荷耦合器件(CCD)、照 相机和计算机。该系统包含用于运行仪器和用于分析数据的软件。5'- 核酸酶测定数据最初表述为Ct或循环阈值。如上所讨论的，在每个 循环期间记录荧光值且荧光值代表在扩增反应中扩增至该点的产物 的量。首次记录到荧光信号为统计学上显著时的点为循环阈值(Ct)。
为了使误差和样品间变化的影响最小化，RT-PCR通常使用内 标物进行。理想的内标物在不同组织间以恒定的水平表达并且不受实 验处理的影响。最常用于对基因表达模式进行归一化的RNA是管家 基因甘油醛-3-磷酸脱氢酶(GAPDH)和β-肌动蛋白的mRNA。
RT-PCR技术的较新变化形式是实时定量PCR，其通过双标记 的荧光生成探针(即TaqManTM探针)测量PCR产物累积。实时PCR 与定量竞争PCR(其中每个靶序列的内部竞争物均用于归一化)以及 定量比较PCR(其使用样品内包含的归一化基因或用于RT-PCR的管 家基因)均相容。进一步的细节参见，例如Held等人,Genome Research 6:986-994(1996)。
G.数据处理
上述测定获得的值可手动计算并存储。或者，上述步骤可完全 或部分地由计算机程序产品进行。因此，本公开提供了包括计算机可 读存储介质的计算机程序产品，该计算机可读存储介质具有存储在其 上的计算机程序。该程序在被计算机读取时，可基于从来自个体的一 个或多个生物样品的分析获得的值(例如，基因或蛋白质表达水平、 归一化、标准化、取阈和从测定的值到临床结果得分和/或临床状态或 阶段的文本或图形描述的转换以及相关信息)来执行相关计算。该计 算机程序产品在其中存储用于执行计算的计算机程序。
本公开提供了用于执行数据采集和处理或计算上述软件程序的 系统，该系统通常包括：a)中央计算环境；b)输入设备，其可操作 地连接到所述计算环境，以接收患者数据，其中所述患者数据可以包 括，例如基因或蛋白质表达水平或从使用来自患者的生物样品的测定 获得的其他值，或质谱数据或由本公开提供的任何测定的数据；c) 输出设备，其连接至所述计算环境，以向用户(例如，医务人员)提 供信息；以及d)由中央计算环境(例如，处理器)执行的算法，其 中该算法基于由所述输入设备接收的数据来执行，并且其中所述算法 计算表达得分、取阈或本文描述的其他功能。本公开提供的方法也可 以是整体或部分自动化的。
H.受试者
生物样品从想要确定其患有结肠肿瘤或息肉的可能性的受试者 采集。本公开提供了可为健康且无症状的受试者。在各个实施方案中， 受试者是健康的、无症状的且年龄在20-50岁之间。在各个实施方案 中，受试者是健康且无症状的并且没有腺瘤或息肉的家族史。在各个 实施方案中，受试者是健康且无症状的并且从未接受过结肠镜检查。 本公开还提供了正在接受作为例行检查的一部分或用于建立生物标 志物的基线水平的检测的健康受试者。
本公开提供了没有结肠直肠癌的症状、没有结肠直肠癌家族史 且没有经识别的结肠直肠癌风险因素的受试者。本公开提供了没有结 肠直肠癌的症状、没有结肠直肠癌家族史且没有除年龄之外的经识别 的结肠直肠癌风险因素的受试者。
生物样品也可以从已根据其家族史确定具有结肠直肠息肉或癌 症的高风险、先前曾治疗结肠直肠息肉或癌症和或处于缓解期的受试 者采集。生物样品还可从表现出已知与结肠直肠癌相关的身体症状的 受试者、通过筛选测定(例如，粪便隐血试验或乙状结肠镜检查)或 直肠数字检查(rectal digital exam)或刚性或柔性结肠镜检查或CT 扫描或其他X射线技术确认的受试者采集。生物样品也可从目前正在 经受治疗的受试者采集，以确定他们正在接受的疗法或治疗的有效性。
I.生物样品
生物标志物可以在不同类型的生物样品中测量。该样品优选来 自汇集并概括了整个系统的生物样品。本公开中有用的生物样品类型 的实例包括但不限于以下的一种或多种：尿、粪便、泪液、全血、血 清、血浆、血液成分、骨髓、组织、细胞、器官、唾液、脸颊拭子、淋巴液、脑脊髓液、病变渗出物和由身体产生的其他流体。该生物标 志物也可从冷冻的、固定的、石蜡包埋的或新鲜的活检样品中提取。
IV.生物标志物和生物标志物谱
本公开的生物标志物允许在健康个体与患有结肠息肉或处于发 展结肠息肉的风险下的个体之间以及在结肠息肉的不同状态(例如增 生的、恶性的、癌或肿瘤亚型)之间进行区分。具体地，本公开对生 物标志物的发现提供了有助于结肠息肉和结肠癌的临床评价和管理 的诊断方法、试剂盒。
可用于结肠息肉的临床评价和管理的生物标志物包括下列蛋白 质(UNIproteinID号)的全蛋白、肽片段、核酸或过渡离子： SPB6_HUMAN、FRIL_HUMAN、P53_HUMAN、1A68_HUMAN、 ENOA_HUMAN、TKT_HUMAN及其组合。
可用于结肠息肉的临床评价和管理的生物标志物包括下列蛋白 质(UNIproteinID号)的全蛋白、肽片段、核酸或过渡离子： SPB6_HUMAN、FRIL_HUMAN、P53_HUMAN、1A68_HUMAN、 ENOA_HUMAN、TKT_HUMAN、TSG6_HUMAN、TPM2_HUMAN、 ADT2_HUMAN、FHL1_HUMAN、CCR5_HUMAN、CEAM5_HUMAN、 SPON2_HUMAN、1A68_HUMAN、RBX1_HUMAN、COR1C_HUMAN、 VIME_HUMAN、PSME3_HUMAN及其组合。
可用于结肠息肉的临床评价和管理的生物标志物包括下列蛋白 质(UNIproteinID号)的全蛋白、肽片段、核酸或过渡离子： SPB6_HUMAN、FRIL_HUMAN、P53_HUMAN、1A68_HUMAN、 ENOA_HUMAN和TKT_HUMAN、TSG6_HUMAN、TPM2_HUMAN、 ADT2_HUMAN、FHL1_HUMAN、CCR5_HUMAN、CEAM5_HUMAN、 SPON2_HUMAN、1A68_HUMAN、RBX1_HUMAN、COR1C_HUMAN、 VIME_HUMAN、PSME3_HUMAN、MIC1_HUMAN、STK11_HUMAN、 IPYR_HUMAN、SBP1_HUMAN、PEBP1_HUMAN、CATD_HUMAN、 HPT_HUMAN、ANXA5_HUMAN、ALDOA_HUMAN、 LAMA2_HUMAN、CATZ_HUMAN、ACTB_HUMAN、AACT_HUMAN 及其组合。
可用于结肠息肉的临床评价和管理的生物标志物包括图12中 的过渡离子。
通过本公开的方法从全血清中鉴定出的生物标志物包括与下列 蛋白质(UNIprotein ID号)相对应的全蛋白、肽片段、核酸或过渡离 子：细胞质肌动蛋白1(ACTB_HUMAN)(SEQ ID NO：1)、肌动 蛋白γ-肠平滑肌前体(ACTH_HUMAN)(SEQ ID NO：2)、血管 紧张素原前体(ANGT_HUMAN)(SEQ ID NO：3)、腺苷高半胱 氨酸酶(SAHH_HUMAN)(SEQ ID NO：4)、醛糖还原酶 (ALDR_HUMAN)(SEQ ID NO：5)、RAC-α丝氨酸/苏氨酸-蛋白 激酶(AKT1_HUMAN)(SEQ ID NO：6)、血清白蛋白前体 (ALBU_HUMAN)(SEQ ID NO：7)、视黄醛脱氢酶1(AL1A1_HUMAN)(SEQ ID NO：8)、醛脱氢酶X线粒体前体 (AL1B1_HUMAN)(SEQ ID NO：9)、果糖-二磷酸醛缩酶A (ALDOA_HUMAN)(SEQ ID NO：10)、α-淀粉酶2B前体 (AMY2B_HUMAN)(SEQID NO：11)、膜联蛋白A1 (ANXA1_HUMAN)(SEQ ID NO：12)、膜联蛋白A3 (ANXA3_HUMAN)(SEQID NO：13)、膜联蛋白A4 (ANXA4_HUMAN)(SEQ ID NO：14)、膜联蛋白A5 (ANXA5_HUMAN)(SEQID NO：15)、腺瘤性结肠息肉病蛋白 (APC_HUMAN)(SEQ ID NO：16)、载脂蛋白A-I前体(APOA1_HUMAN)(SEQ ID NO：17)、载脂蛋白C-I前体 (APOC1_HUMAN)(SEQ ID NO：18)、β-2-糖蛋白1前体 (APOH_HUMAN)(SEQ ID NO：19)、Rho GDP解离抑制剂1 (GDIR1_HUMAN)(SEQID NO：20)、ATP合酶β亚基线粒体前 体(ATPB_HUMAN)(SEQ ID NO：21)、具有锚蛋白重复序列的 B细胞支架蛋白(BANK1_HUMAN)(SEQ ID NO：22)、未表征 的蛋白C18orf8(MIC1_HUMAN)(SEQ ID NO：23)、推定的未表 征的蛋白C1orf195(CA195_HUMAN)(SEQ ID NO：24)、补体 C3前体(CO3_HUMAN)(SEQ ID NO：25)、补体成分C9前体 (CO9_HUMAN)(SEQ ID NO：26)、碳酸酐酶1(CAH1_HUMAN) (SEQ ID NO：27)、碳酸酐酶2(CAH2_HUMAN)(SEQ ID NO：28)、钙网蛋白前体(CALR_HUMAN)(SEQ ID NO：29)、巨噬 细胞加帽蛋白(CAPG_HUMAN)(SEQID NO：30)、信号转导蛋 白CD24前体(CD24_HUMAN)(SEQ ID NO：31)、CD63抗原 (CD63_HUMAN)(SEQ ID NO：32)、胞苷脱氨酶(CDD_HUMAN) (SEQ ID NO：33)、癌胚抗原相关细胞粘附分子3(CEAM3_HUMAN) (SEQ ID NO：34)、癌胚抗原相关细胞粘附分子5(CEAM5_HUMAN)(SEQ ID NO：35)、癌胚抗原相关细胞粘附分子6(CEAM6_HUMAN) (SEQ ID NO：36)、绒毛膜促性腺激素β亚基前体(CGHB_HUMAN) (SEQ ID NO：37)、几丁质酶-3样蛋白1前体(CH3L1_HUMAN) (SEQ ID NO：38)、肌酸激酶B型(KCRB_HUMAN)(SEQ ID NO： 39)、C型凝集素结构域家族4成员D(CLC4D_HUMAN)(SEQ ID NO：40)、簇蛋白前体(CLUS_HUMAN)(SEQ ID NO：41)、钙调理蛋白-1(CNN1_HUMAN)(SEQ ID NO：42)、冠蛋白-1C (COR1C_HUMAN)(SEQ ID NO：43)、C-反应蛋白前体 (CRP_HUMAN)(SEQ ID NO：44)、巨噬细胞集落刺激因子1前 体(CSF1_HUMAN)(SEQ ID NO：45)、连环蛋白β-1(CTNB1_HUMAN) (SEQ ID NO：46)、组织蛋白酶D前体(CATD_HUMAN)(SEQ ID NO：47)、组织蛋白酶S前体(CATS_HUMAN)(SEQ ID NO： 48)、组织蛋白酶Z前体(CATZ_HUMAN)(SEQ ID NO：49)、 滞蛋白-1(CUL1_HUMAN)(SEQ ID NO：50)、细胞质天冬氨酸-tRNA 连接酶(SYDC_HUMAN)(SEQ ID NO：51)、嗜中性粒细胞防御 素1(DEF1_HUMAN)(SEQID NO：52)、嗜中性粒细胞防御素3 (DEF3_HUMAN)(SEQ ID NO：53)、结蛋白(DESM_HUMAN)(SEQ ID NO：54)、二肽基肽酶4(DPP4_HUMAN)(SEQ ID NO： 55)、二氢嘧啶酶相关蛋白2(DPYL2_HUMAN)(SEQ ID NO：56)、 细胞质动力蛋白1重链1(DYHC1_HUMAN)(SEQ ID NO：57)、δ(3,5)-δ(2,4)-二烯酰-CoA异构酶线粒体前体(ECH1_HUMAN)(SEQ ID NO：58)、延伸因子2(EF2_HUMAN)(SEQ ID NO：59)、真 核起始因子4A-III(IF4A3_HUMAN)(SEQ ID NO：60)、α-烯醇 化酶(ENOA_HUMAN)(SEQ ID NO：61)、埃兹蛋白(EZRI_HUMAN) (SEQ ID NO：62)、Niban样蛋白2(NIBL2_HUMAN)(SEQ ID NO：63)、Seprase(SEPR_HUMAN)(SEQ ID NO：64)、仅F框蛋白4(F-box only protein 4)(FBX4_HUMAN)(SEQ ID NO：65)、纤 维蛋白原β链前体(FIBB_HUMAN)(SEQ ID NO：66)、纤维蛋 白原γ链(FIBG_HUMAN)(SEQ ID NO：67)、四个半LIM结构域蛋白1(FHL1_HUMAN)(SEQ ID NO：68)、细丝蛋白-A (FLNA_HUMAN)(SEQ ID NO：69)、包含FERM结构域的蛋白 3(FRMD3_HUMAN)(SEQ ID NO：70)、铁蛋白重链(FRIH_HUMAN) (SEQ IDNO：71)、铁蛋白轻链(FRIL_HUMAN)(SEQ ID NO： 72)、组织α-L-岩藻糖苷酶前体(FUCO_HUMAN)(SEQ ID NO： 73)、γ-氨基丁酸受体亚基α-1前体(GBRA1_HUMAN)(SEQ ID NO： 74)、甘油醛-3-磷酸脱氢酶(G3P_HUMAN)(SEQ ID NO：75)、 甘氨酸-tRNA连接酶(SYG_HUMAN)(SEQ ID NO：76)、生长/ 分化因子15前体(GDF15_HUMAN)(SEQ ID NO：77)、凝溶胶 蛋白前体(GELS_HUMAN)(SEQ ID NO：78)、谷胱甘肽S-转移 酶P(GSTP1_HUMAN)(SEQ ID NO：79)、透明质酸结合蛋白2 前体(HABP2_HUMAN)(SEQ ID NO：80)、肝细胞生长因子前体 (HGF_HUMAN)(SEQ ID NO：81)、HLA I类组织相容性抗原 A-68α链(1A68_HUMAN)(SEQ ID NO：82)、高速泳动族蛋白 B1(HMGB1_HUMAN)(SEQ ID NO：83)、核内不均一核糖核蛋 白A1(ROA1_HUMAN)(SEQ ID NO：84)、核内不均一核糖核蛋 白A2/B1(ROA2_HUMAN)(SEQ ID NO：85)、核内不均一核糖 核蛋白F(HNRPF_HUMAN)(SEQ ID NO：86)、触珠蛋白前体 (HPT_HUMAN)(SEQID NO：87)、热休克蛋白HSP 90-β (HS90B_HUMAN)(SEQ ID NO：88)、内质网素(Endoplasmin) 前体(ENPL_HUMAN)(SEQ ID NO：89)、Stress-70蛋白线粒体 前体(Stress-70protein,mitochondrial precursor)(GRP75_HUMAN) (SEQ ID NO：90)、热休克蛋白β-1(HSPB1_HUMAN)(SEQ ID NO：91)、线粒体60kDa热休克蛋白(CH60_HUMAN)(SEQ ID NO： 92)、骨唾液蛋白2(SIAL_HUMAN)(SEQ ID NO：93)、鞭毛内 转运蛋白74同系物(IFT74_HUMAN)(SEQ ID NO：94)、胰岛素 样生长因子I(IGF1_HUMAN)(SEQ ID NO：95)、Igα-2链C区(IGHA2_HUMAN)(SEQ ID NO：96)、白介素-2受体β亚基前体 (IL2RB_HUMAN)(SEQ ID NO：97)、白介素-8(IL8_HUMAN) (SEQ ID NO：98)、白介素-9(IL9_HUMAN)(SEQ ID NO：99)、 GTP酶KRas前体(RASK_HUMAN)(SEQ ID NO：100)、角蛋白 I型细胞骨架19(K1C19_HUMAN)(SEQID NO：101)、角蛋白 II型细胞骨架8(K2C8_HUMAN)(SEQ ID NO：102)、层粘连蛋 白亚基α-2前体(LAMA2_HUMAN)(SEQ ID NO：103)、半乳凝 集素-3(LEG3_HUMAN)(SEQ ID NO：104)、核纤层蛋白-B1前 体(LMNB1_HUMAN)(SEQ ID NO：105)、微管相关蛋白RP/EB 家族成员1(MARE1_HUMAN)(SEQ ID NO：106)、DNA复制许 可因子MCM4(MCM4_HUMAN)(SEQ ID NO：107)、巨噬细胞 游走抑制因子(MIF_HUMAN)(SEQ ID NO：108)、基质溶解素 前体(MMP7_HUMAN)(SEQ ID NO：109)、基质金属蛋白酶9 前体(MMP9_HUMAN)(SEQ ID NO：110)、B淋巴细胞抗原CD20 (CD20_HUMAN)(SEQ ID NO：111)、肌球蛋白轻链多肽6 (MYL6_HUMAN)(SEQ ID NO：112)、肌球蛋白调节轻链多肽9 (MYL9_HUMAN)(SEQ ID NO：113)、核苷二磷酸激酶A (NDKA_HUMAN)(SEQ ID NO：114)、烟酰胺N-甲基转移酶 (NNMT_HUMAN)(SEQ ID NO：115)、α-1-酸性糖蛋白1前体 (A1AG1_HUMAN)(SEQ ID NO：116)、磷酸烯醇丙酮酸羧激酶 [GTP]线粒体前体(PCKGM_HUMAN)(SEQ ID NO：117)、蛋白 质二硫键异构酶A3前体(PDIA3_HUMAN)(SEQ IDNO：118)、 蛋白质二硫键异构酶A6前体(PDIA6_HUMAN)(SEQ ID NO：119)、 吡哆醛激酶(PDXK_HUMAN)(SEQ ID NO：120)、磷脂酰乙醇胺 结合蛋白1(PEBP1_HUMAN)(SEQ ID NO：121)、磷脂酰肌醇转 移蛋白α同种型(PIPNA_HUMAN)(SEQ ID NO：122)、丙酮酸 激酶同工酶M1/M2(KPYM_HUMAN)(SEQ ID NO：123)、尿激 酶型纤溶酶原激活剂前体(UROK_HUMAN)(SEQID NO：124)、 无机焦磷酸酶(IPYR_HUMAN)(SEQ ID NO：125)、过氧化物氧 还蛋白-1(PRDX1_HUMAN)(SEQ ID NO：126)、丝氨酸/苏氨酸 -蛋白激酶D1(KPCD1_HUMAN)(SEQ IDNO：127)、催乳素 (PRL_HUMAN)(SEQ ID NO：128)、跨膜γ-羧基谷氨酸蛋白4 前体(TMG4_HUMAN)(SEQ ID NO：129)、蛋白酶体激活剂复合 物亚基3(PSME3_HUMAN)(SEQ ID NO：130)、磷脂酰肌醇3,4,5- 三磷酸3-磷酸酶和双特异性蛋白质磷酸酶PTEN(PTEN_HUMAN) (SEQ IDNO：131)、黏着斑激酶1(FAK1_HUMAN)(SEQ ID NO： 132)、蛋白质酪氨酸激酶2-β(FAK2_HUMAN)(SEQ ID NO：133)、 E3泛素-蛋白质连接酶RBX1(RBX1_HUMAN)(SEQ ID NO：134)、 再生胰岛衍生蛋白4前体(REG4_HUMAN)(SEQ ID NO：135)、 转化蛋白RhoA(RHOA_HUMAN)(SEQID NO：136)、Rho相关 GTP结合蛋白RhoB(RHOB_HUMAN)(SEQ ID NO：137)、Rho 相关GTP结合蛋白RhoC(RHOC_HUMAN)(SEQ ID NO：138)、 40S核糖体蛋白SA(RSSA_HUMAN)(SEQ ID NO：139)、核糖 体结合蛋白1(RRBP1_HUMAN)(SEQ ID NO：140)、蛋白S100-A11 (S10AB_HUMAN)(SEQ ID NO：141)、蛋白S100-A12 (S10AC_HUMAN)(SEQ ID NO：142)、蛋白S100-A8 (S10A8_HUMAN)(SEQ ID NO：143)、蛋白S100-A9 (S10A9_HUMAN)(SEQ ID NO：144)、血清淀粉样蛋白A-1蛋 白(SAA1_HUMAN)(SEQ ID NO：145)、血清淀粉样蛋白A-2蛋 白前体(SAA2_HUMAN)(SEQ ID NO：146)、促泌素(SEGN_HUMAN) (SEQ ID NO：147)、血清学定义结肠癌抗原3(SDCG3_HUMAN) (SEQ ID NO：148)、琥珀酸脱氢酶[泛醌]黄素蛋白亚基线粒体前体 (DHSA_HUMAN)(SEQ ID NO：149)、硒结合蛋白1(SBP1_HUMAN) (SEQ ID NO：150)、P-选择蛋白糖蛋白配体1前体(SELPL_HUMAN) (SEQ ID NO：151)、隔蛋白-9(SEPT9_HUMAN)(SEQ ID NO：152)、α-1抗胰蛋白酶前体(A1AT_HUMAN)(SEQ ID NO：153)、 α-1抗胰凝乳蛋白酶前体(AACT_HUMAN)(SEQ ID NO：154)、 白细胞弹性蛋白酶抑制剂(ILEU_HUMAN)(SEQ ID NO：155)、 丝氨酸蛋白酶抑制蛋白B6(SPB6_HUMAN)(SEQ ID NO：156)、 剪接因子3B亚基3(SF3B3_HUMAN)(SEQ ID NO：157)、S相 激酶相关蛋白1(SKP1_HUMAN)(SEQ ID NO：158)、ADP/ATP 移位酶2(ADT2_HUMAN)(SEQ ID NO：159)、胰分泌型胰蛋白 酶抑制剂(ISK1_HUMAN)(SEQ ID NO：160)、脊椎蛋白-2 (SPON2_HUMAN)(SEQ ID NO：161)、骨桥蛋白(OSTP_HUMAN) (SEQ ID NO：162)、原癌基因酪氨酸蛋白激酶Src(SRC_HUMAN) (SEQ ID NO：163)、丝氨酸/苏氨酸-蛋白激酶STK11 (STK11_HUMAN)(SEQ ID NO：164)、核内不均一核糖核蛋白Q(HNRPQ_HUMAN)(SEQ ID NO：165)、T细胞急性淋巴细胞 性白血病蛋白1(TAL1_HUMAN)(SEQID NO：166)、血清铁传 递蛋白前体(TRFE_HUMAN)(SEQ ID NO：167)、血小板反应蛋 白-1前体(TSP1_HUMAN)(SEQ ID NO：168)、金属蛋白酶抑制 剂1(TIMP1_HUMAN)(SEQ ID NO：169)、转酮醇酶(TKT_HUMAN) (SEQ ID NO：170)、肿瘤坏死因子诱导型基因6蛋白前体 (TSG6_HUMAN)(SEQ ID NO：171)、肿瘤坏死因子受体超家族 成员10B(TR10B_HUMAN)(SEQ ID NO：172)、肿瘤坏死因子 受体超家族成员6B(TNF6B_HUMAN)(SEQ ID NO：173)、细 胞肿瘤抗原p53(P53_HUMAN)(SEQ ID NO：174)、原肌球蛋白 β链(TPM2_HUMAN)(SEQ ID NO：175)、翻译控制肿瘤蛋白 (TCTP_HUMAN)(SEQ ID NO：176)、热休克蛋白75kDa线粒 体前体(TRAP1_HUMAN)(SEQ ID NO：177)、硫代硫酸硫基转 移酶(THTR_HUMAN)(SEQ ID NO：178)、微管蛋白β-1链 (TBB1_HUMAN)(SEQ ID NO：179)、UDP-葡萄糖6-脱氢酶 (UGDH_HUMAN)(SEQ ID NO：180)、UTP-葡萄糖-1-磷酸尿苷 酰转移酶(UGPA_HUMAN)(SEQ ID NO：181)、血管内皮生长因子A(VEGFA_HUMAN)(SEQ ID NO：182)、绒毛蛋白-1 (VILI_HUMAN)(SEQ ID NO：183)、波形蛋白(VIME_HUMAN) (SEQ ID NO：184)、泛酰巯基乙胺酶前体(VNN1_HUMAN)(SEQ ID NO：185)、14-3-3蛋白ζ/δ(1433Z_HUMAN)(SEQ ID NO：186)、 C-C趋化因子受体5型(CCR5_HUMAN)(SEQID NO：187)或血 浆α-L-岩藻糖苷酶(FUCO2_HUMAN)(SEQ ID NO：188)。本公 开的方法预期确定上文提供的至少一种、至少两种、至少三种、至少 四种、至少五种、至少六种、至少七种、至少八种、至少九种生物标 志物的表达水平。该方法可包括确定上文提供的至少十种、至少十五 种或至少二十种生物标志物的表达水平。
对于本公开的所有方面，所述方法可进一步包括确定本文提供 的至少两种生物标志物的表达水平。进一步预期：本公开的方法可进 一步包括确定本文提供的至少三种、至少四种、至少五种、至少六种、 至少七种、至少八种、至少九种生物标志物的表达水平。该方法可包 括确定本文提供的至少十种、至少十五种或至少二十种生物标志物的 表达水平。
通过本公开的方法从全血清中鉴定的生物标志物包括与下列蛋 白质相对应的肽/蛋白质片段或基因：SCDC26(CD26)、CEA分子5 (CEACAM5)、CA195(CCR5)、CA19-9、M2PK(PKM2)、TIMP1、P- 选择蛋白(SELPLG)、VEGFA、HcGB(CGB)、绒毛蛋白(VILLIN)、 TATI(SPINK1)和A-L-岩藻糖苷酶(FUCA2)。包括上述蛋白质或基因 中的两种、三种、四种、五种、六种、七种、八种、九种、十种、十 一种和全部十二种的群组。这样的群组可排除这一组内的蛋白质或基 因，或者可排除另外的蛋白质或基因，或可进一步包含另外的蛋白质。
通过本公开的方法从全血清中鉴定的生物标志物包括与下列蛋 白质相对应的肽/蛋白质片段或基因：ANXA5、GAPDH、PKM2、 ANXA4、GARS、RRBP1、KRT8、SYNCRIP、S100A9、ANXA3、 CAPG、HNRNPF、PPA1、NME1、PSME3、AHCY、TPT1、HSPB1 和RPSA。包括上述蛋白质或基因中的两种、三种、四种、五种、六 种、七种、八种、九种、十种、十一种、十二种、十三种、十四种、 十五种、十六种、十七种、十八种和所有十九种的群组。这样的群组 可排除这一组内的蛋白质或基因，或者可排除另外的蛋白质或基因， 或可以进一步包含另外的蛋白质。
通过本公开的方法从全血清中鉴定的生物标志物包括与图9中 鉴定的蛋白质相对应的肽/蛋白质片段或基因。包括上述蛋白质或基因 中的两种、三种、四种、五种、六种、七种、八种、九种、十种、十 一种、十二种及更多种的群组。这样的群组可排除这一组内的蛋白质 或基因，或者可排除另外的蛋白质，或可以进一步包含另外的蛋白质。
已知由于蛋白质可以以各种形式缔合以形成各种蛋白质复合物， 因此蛋白质通常以多种不同的形式存在于样品中。这些形式可由翻译 前和翻译后修饰中的任一种或两种产生。翻译前修饰形式包括等位基 因变体、剪接变体和RNA编辑形式。在这样的情况下，已知基因表 达产物将与人类数据库中定义的蛋白质呈现各种同源性。因此，本公 开认识到，可以存在所定义的生物标志物的各种形式。例如，所述序 列同源性选自大于75％、大于80％、大于85％、大于90％、大于95％ 以及大于99％。此外，可以存在生物标志物的翻译后修饰形式。翻译 后修饰形式包括但不限于由蛋白质生物标志物的蛋白水解裂解(例如， 亲本蛋白质的片段)、糖基化、磷酸化、脂化、氧化、甲基化、半胱 氨酰化(cystinylation)、磺化和乙酰化产生的形式。
本公开的生物标志物包括全长蛋白质、它们相应的RNA或 DNA及所有的修饰形式。该生物标志物的修饰形式包括，例如所公 开的生物标志物和它们相应的编码它们的RNA或DNA的任何剪接变 体。在某些情况下，蛋白质或它们相应的RNA或DNA的修饰形式或 截短形式可在诊断上表现出比全长蛋白质更好的鉴别能力。
蛋白质、多肽或肽的截短形式或片段通常是指所述蛋白质、多 肽或肽的N-末端和/或C-末端缺失或截短形式。该术语涵盖通过任何 机制，诸如但不限于，通过所述肽、多肽或蛋白质例如在体内或体外 的选择性翻译、外切和/或内切蛋白水解和/或降解(例如，通过物理、 化学和/或酶促蛋白水解)产生的片段。非限制性地，蛋白质、多肽或 肽的截短形式或片段可以代表所述蛋白质、多肽或肽的至少约5％或 至少约10％(例如>20％、>30％或>40％，如>50％，例如>60％、>70％ 或>80％或甚至90％或>95％)的氨基酸序列。
非限制性地，蛋白质的截短形式或片段可包含相应全长蛋白质 的5个连续氨基酸或10个连续氨基酸或20个连续氨基酸或30个连 续氨基酸或多于50个连续氨基酸，例如60、70、80、90、100、200、 300、400、500或600个连续氨基酸的序列。
在一些情况下，与相应成熟的全长蛋白质或其可溶性或血浆循 环形式相比，片段可以是N末端和/或C末端截短1至约20个氨基酸， 如1至约15个氨基酸或者1至约10个氨基酸或者1至约5个氨基酸。
本公开的任何蛋白质生物标志物如肽、多肽或蛋白质及其片段 也可涵盖所述标志物、肽、多肽或蛋白质和片段的修饰形式，如具有 表达后修饰，包括但不限于，诸如磷酸化、糖基化、脂化、甲基化、 半胱氨酰化、磺化、谷胱甘肽化、乙酰化、甲硫氨酸氧化成甲硫氨酸 亚砜或甲硫氨酸砜等修饰。
在一些情况下，给定蛋白质、多肽或肽的片段可通过所述蛋白 质、多肽或肽的体外蛋白水解来实现，以从样品获得可有利地检测的 肽。例如，这样的蛋白水解可通过合适的物理、化学和/或酶试剂，例 如蛋白酶、优选内切蛋白酶(即，在蛋白质、多肽或肽链内进行内部 切割的蛋白酶)来实现。
内切蛋白酶的合适的非限制性实例包括但不限于，丝氨酸蛋白 酶(EC 3.4.21)、苏氨酸蛋白酶(EC 3.4.25)、半胱氨酸蛋白酶(EC 3.4.22)、天冬氨酸蛋白酶(EC 3.4.23)、金属蛋白酶(EC 3.4.24) 和谷氨酸蛋白酶。示例性的非限制性内切蛋白酶包括胰蛋白酶、糜蛋 白酶、弹性蛋白酶、产酶溶杆菌内切蛋白酶Lys-C、金黄色葡萄球菌 内切蛋白酶Glu-C(肽链内切酶V8)或溶组织梭菌内切蛋白酶Arg-C (梭菌蛋白酶)。
优选地，所述蛋白水解可通过胰蛋白酶型的肽链内切酶(EC 3.4.21.4)，优选胰蛋白酶，诸如但不限于，来自牛胰脏、人胰脏、猪 胰脏的胰蛋白酶、重组胰蛋白酶、Lys-乙酰化的胰蛋白酶、溶液中的 胰蛋白酶、固定于固体支持物的胰蛋白酶等的制剂来实现。胰蛋白酶 尤其因裂解的高特异性和高效性而特别有用。本公开还提供了任何胰 蛋白酶样蛋白酶(即具有与胰蛋白酶的特异性相似的特异性)的使用。 另外，化学试剂可用于蛋白水解。仅举例而言，CNBr可在Met处裂 解；BNPS-粪臭素可以在Trp处裂解。用于处理的条件，例如蛋白质 浓度、酶或化学试剂浓度、pH、缓冲液、温度、时间，可由技术人员 根据所用酶或化学试剂来确定。其他已知的或尚未鉴定的酶可基于它 们的裂解特异性和频率在本公开中使用，以获得期望的肽形式。
在一些情况下，片段化的蛋白质或肽可以是N-末端和/或C-末 端截短的，且为N-末端(a、b、c-离子)和/或C-末端(x、y、z-离 子)截短的蛋白质或肽的一个或全部过渡离子。例如，如果肽片段由 氨基酸序列IAELLSPGSVDPLTR组成，则该肽片段的过渡离子生物 标志物可包括表1中提供的下列过渡离子生物标志物中的一种或多种。
表1：肽序列IAELLSPGSVDPLTR的所有过渡离子的实例
本公开的生物标志物包括SCDC26(CD26)、CEA分子5 (CEACAM5)、CA195(CCR5)、CA19-9、M2PK(PKM2)、TIMP1、 P-选择蛋白(SELPLG)、VEGFA、HcGB(CGB)、绒毛蛋白、TATI(SPINK1)和A-L-岩藻糖苷酶(FUCA2)的结合配偶体。包括上述 蛋白质中的两种、三种、四种、五种、六种、七种、八种、九种、十 种、十一种和所有十二种的群组。这样的群组可排除这一组内的蛋白 质，或可排除另外的蛋白质，或可以进一步包含另外的蛋白质。
本公开的生物标志物包括ANXA5、GAPDH、PKM2、ANXA4、 GARS、RRBP1、KRT8、SYNCRIP、S100A9、ANXA3、CAPG、HNRNPF、 PPA1、NME1、PSME3、AHCY、TPT1、HSPB1和RPSA的结合配 偶体。包括上述蛋白质中的两种、三种、四种、五种、六种、七种、 八种、九种、十种、十一种、十二种、十三种、十四种、十五种、十 六种、十七种、十八种和所有十九种的群组。这样的群组可排除这一 组内的蛋白质，或可排除另外的蛋白质，或可以进一步包含另外的蛋 白质。
如本文所教导的示例性的人标志物、核酸、蛋白质或多肽可以 如NCBI Genbank(http://www.ncbi.nlm.nih.gov/)或Swissprot/Uniprot (http://www.uniprot.org/)登录号下所注释的。在一些情况下，所述 序列可以是如本文所教导的标志物、核酸、蛋白质或多肽的前体(例 如，前蛋白质)的序列，并且可包含从成熟分子加工除去的部分。在 一些情况下，虽然可能仅公开一个或多个同种型，但旨在涵盖该序列 的所有同种型。
本公开的生物标志物包括图9中鉴定的蛋白质的结合配偶体。 包括上述蛋白质中的两种、三种、四种、五种、六种、七种、八种、 九种、十种、十一种、十二种和更多种的群组。这样的群组可排除这 一组内的蛋白质，或可排除另外的蛋白质，或可进一步包含另外的蛋白质。
上述鉴定的生物标志物是如根据分子量和部分序列确定的，通 过本公开的方法鉴定的生物标志物的实例，并且仅仅作为说明性实例 且并不意在以任何方式限制本公开。可用于检测一种或多种生物标志 物或修饰的生物标志物的合适的方法在本文中进行了描述。在某一方 面，本公开提供了对生物样品进行关于存在选自代谢物、DNA序列、 RNA序列及其组合的一种或多种分析物的附加生物标志物的分析。 本文所列出的生物标志物可进一步与其他信息，如遗传分析，例如受 试者的全基因组DNA或RNA测序进行组合。
本公开的所有方面也可采用有限数目的公开的生物标志物、它 们的结合配偶体、剪接变体和相应的DNA和RNA来实施。
除了相应的DNA和RNA外，在本公开提供的生物标志物的 DNA和RNA内发现的变异也可提供用于区分个体的临床状态的手段。 可在本公开的方法中使用的此类DNA和RNA遗传变异标志物的实例 包括但不限于限制性片段长度多态性、单核苷酸DNA多态性、单核 苷酸cDNA多态性、单核苷酸RNA多态性、单核苷酸RNA多态性、 插入、缺失、插入缺失(indel)、微卫星重复(简单序列重复)、小 卫星重复(可变数目的串联重复)、短串联重复、转座因子、随机扩 增多态性DNA和扩增片段长度多态性。
生物标志物谱
本公开的方法还提供了将要生成并用于商业医疗诊断产品或试 剂盒的生物标志物谱。
所述方法提供了将要以多种方式确定的并且可以是使用诸如比 例或其他更复杂的关联方法或算法(例如，基于规则的方法)的方法 确定的可测量生物标志物或生物标志物的多个方面的组合的生物标 志物谱。生物标志物谱可包含至少两个测量值，其中该测量值可对应 于相同或不同的生物标志物。生物标志物谱还可包含至少3、4、5、 10、15、20、25、30、35、40、45、50、55个或更多个测量值。在一 些应用中，生物标志物谱包含数百个或甚至数千个测量值。生物标志 物谱可包含仅来自个体或包含来自个体的测量值以及来自已知与个 体相关的分层群体或已知与个体无关的分层群体或两者的测量值。
此外，生物标志物谱还提供了本文提供的可各自独立地且独立 地评估的生物标志物的存在与否或量，或者此类其他生物标志物的存 在与否和/或量可包含在本文公开的方法中建立的受试者谱或参考谱 内。
V.生物标志物的应用
通常，所述方法至少包括以下步骤：(a)获得生物样品，(b) 进行生物样品分析，(c)将该样品与参照对照进行比较，以及(d) 将蛋白质的存在或量与受试者的结肠息肉状态相关联。在本公开的一 些方面，定量包括将测量值相对于已知处在恒定水平的内标对照进行 归一化。在本公开的其他方面，定量包括与来自健康非患病无肿瘤的 受试者的参考对照进行比较并确定差异表达。在本公开的其他方面， 定量包括与来自患有肿瘤的患病受试者的参考对照进行比较并确定 差异表达。从该方法获得的数据可用于创建“谱”，该谱用于预测疾病 状态、复发或对治疗的反应。一旦创建了谱，则可将试验结果与标准 谱进行比较，并可得到与反应的相关性。应当理解，通常对描述的谱 进行优化。本公开并不限于这种特定的生物标志物谱的使用。提供有 用信息的一种或多种标志物的任何组合可在本公开的方法中使用。例 如，应当理解，可以加入或从签名中减去一种或多种标志物，同时保 持该签名产生有用信息的能力。
在本公开的一个方面，所有或一些生物标志物或生物标志物的 组合的定量可用于检测受试者中存在结肠息肉的可能性。在本公开的 另一方面，所有或一些生物标志物或生物标志物的组合可用于通过鉴 定受试者样品的一种或多种性质来检测结肠肿瘤的性质，包括但不限 于，良性的存在、息肉的类型、癌变前的阶段、发育异常的程度、亚 型腺瘤性息肉或良性结肠肿瘤疾病的亚型以及预后。在本公开的一个 方面，所有或一些生物标志物或生物标志物的组合可用于检测患上结 肠肿瘤或息肉的可能性。在本公开的一个方面，所有或一些生物标志 物或生物标志物的组合可用于排除结肠肿瘤或息肉的存在，即确定受 试者不存在结肠息肉、癌或两者均不存在。在本公开的另一方面，所 有或一些生物标志物或生物标志物的组合可用于确定肿瘤的性质，即， 它是否是良性肿瘤息肉、恶性肿瘤、腺瘤性息肉、有蒂息肉或无蒂息 肉型。
在本公开的一个方面，所有或一些生物标志物或生物标志物的 组合可用于生成报告，该报告有助于结肠直肠癌或结肠肿瘤的临床管 理的下一步骤。在本公开的一个方面，所有或一些生物标志物或生物 标志物的组合可用于监测对结肠直肠癌或结肠肿瘤的各种治疗的反 应性。在本公开的一个方面，所有或一些生物标志物或生物标志物的 组合可用于监测具有患结肠直肠癌或结肠肿瘤的倾向的受试者。在本 公开的一个方面，所有或一些生物标志物或生物标志物的组合可用于 监测受试者的结肠直肠癌或结肠肿瘤的复发。在本公开的一个方面， 所有或一些生物标志物或生物标志物的组合可用于监测受试者的结 肠直肠癌或息肉的复发。
在一些实施方案中，所述方法包括鉴定来自受试者的生物样品 的细胞中的生物标志物的谱，其中所述模式与疾病或状况或反应的可 能性相关联。
在该方法的一些方面，通过由例如定量免疫荧光或基于ELISA 的测定法、流式细胞术或本文提供的其他免疫测定来对蛋白质表达水 平进行定量来检测一种或多种生物标志物或生物标志物谱。在该方法 的一些方面，通过例如使用特异性扩增与DNA或RNA相对应的生物 标志物的引物组的实时PCR对多核苷酸的表达水平进行定量来检测 生物标志物谱。在本公开的另一方面，该谱由包含生物标志物的捕获 特征(例如，抗体、探针等)的生物芯片来检测。生物芯片可根据生 物样品中或来自受试者的多核苷酸例如mRNA的表达水平或者通过 使用例如抗体检测患者样品中的蛋白质的表达水平来检测生物标志 物谱的存在。在另一些实施方案中，通过使用引物组的实时PCR来 检测肿瘤细胞谱，该引物组特异性地扩增包含癌干细胞签名的基因。 在本公开的其他实施方案中，提供了包含多核苷酸或蛋白质(即抗体) 的微阵列，该多核苷酸或蛋白质(即抗体)检测癌干细胞签名的表达 以用于预后。
可将生物样品的生物标志物谱与参考谱进行比较并可确定结果。 在本公开的一个方面，将从本文所述的试验产生的数据与由谱模型定 义的参考谱进行比较，该谱模型由一个或多个生物样品的测量值得到。 可以将试验安排为使得单个患者样品可与考虑到的这些群体一起查 看并被分配给一个群体或其他群体或者两者的混合，并随后使用这种 与患者管理、疗法、预后等的相关性。
在本公开的一个方面，从本文所述的方法和试剂盒检测产生的 数据与可视化手段一起使用，该可视化手段能够指示样品中的所述一 种或多种标志物或片段的量是否在某个阈值水平以上或以下，或者样 品中的所述一种或多种标志物或片段的量是否偏离或不偏离所述一 种或多种标志物或片段的量的参考值，所述参考值表示如本文所教导 的疾病或状况的已知诊断、预测或预后。
在本公开的一个方面，选择从本文所述的方法或试剂盒检测产 生的确定为阈值水平的数据，使得样品中的所述一种或多种标志物和 /或片段的量在所述阈值水平以上或以下(取决于标志物以及疾病或状 况)指示受试者患有相应的疾病或状况或处于患有相应的疾病或状况 的风险下，或者指示受试者的相应的疾病或状况的不良预后，以及样 品中的所述一种或多种标志物和/或片段的量在所述阈值水平以下或 以上(取决于标志物以及疾病或状况)指示受试者不患有如本文所教 导的疾病或状况或不处于患有该疾病或状况的风险下，或者指示受试 者的该疾病或状况的良好预后。
在本公开的一个方面，从本文所述的方法和试剂盒检测产生的 确定样品中的核酸分子或分析物的相对量的数据可有利地表示为相 对于所述另一个值，诸如相对于如本文教导的参考值、权重或等级的 增加或减少，或表示为倍数增加或倍数减少。在第一和第二参数(例 如，第一和第二量)间进行相对比较可以但不是必然需要首先确定所 述第一和第二参数的绝对值。例如，测量方法可以产生所述第一和第 二参数的可量化读数(例如，信号强度)，其中所述读数是所述参数 的值的函数，并且其中可以直接比较所述读数，以产生第一参数相对 于第二参数的相对值，而实际上无需首先将读数转化为相应参数的绝 对值。
A.灵敏度和特异性
灵敏度和特异性是二元分类试验的性能的统计度量。完美的分 类预测指标(predictor)被描述为100％灵敏(即，将来自患病组的所 有人预测为患病)和100％特异(即，不将来自健康组的任何人预测 为患病)；然而，理论上任何分类预测指标将具有最小误差。(Altman DG,Bland JM(1994)."Diagnostic tests Sensitivity andSpecificity". BMJ 308(6943):1552和Loong T(2003)."Understanding sensitivityand specificity with the right side of the brain".BMJ 327(7417):716-719)。
在本公开方法的一个方面，使用全部或一些生物标志物或生物 标志物的组合针对受试者的腺瘤或息肉状态实现了选自大于60％真 阳性、70％真阳性、75％真阳性、85％真阳性、90％真阳性、95％真阳 性或99％真阳性的灵敏度。在本公开方法的一个方面，使用全部或一 些生物标志物或生物标志物的组合针对受试者的腺瘤、癌症或息肉状 态实现了选自大于60％真阴性、70％真阴性、75％真阴性、85％真阴 性、90％真阴性、95％真阴性或99％真阴性的特异性。在本公开方法 的一个方面，使用全部或一些生物标志物或生物标志物的组合排除了 或没有确定结肠直肠癌的存在与否。在本公开方法的一个方面，通过 附加试验如结肠镜检查、其他成像方法或诊断试验或手术来确认腺瘤、 癌症或息肉状态的存在与否。在本公开方法的一个方面，使用全部或 一些生物标志物或生物标志物的组合针对受试者的腺瘤、癌症或息肉 状态实现了选自大于70％真阳性和小于30％真阴性、75％真阳性和小 于25％真阴性、85％真阳性和小于15％真阴性、90％真阳性和小于10％ 真阴性、95％真阳性和小于5％真阴性、或99％真阳性和小于1％真阴 性的灵敏度和特异性。
在本公开方法的一个方面，使用全部或一些生物标志物或生物 标志物的组合针对受试者的结肠直肠癌的存在与否实现了选自大于 70％真阳性、75％真阳性、85％真阳性、90％真阳性、95％真阳性或 99％真阳性的灵敏度。在本公开方法的一个方面，使用全部或一些生 物标志物或生物标志物的组合针对受试者的结肠直肠癌的存在与否 实现了选自大于70％真阴性、75％真阴性、85％真阴性、90％真阴性、 95％真阴性或99％真阴性的特异性。在本公开方法的一个方面，不检 测结肠直肠癌的存在与否。在本公开方法的一个方面，通过附加试验 如结肠镜检查、其他成像方法或诊断试验或手术来确认结肠直肠癌的存在与否。在本公开方法的一个方面，使用全部或一些生物标志物或 生物标志物的组合针对受试者的结肠直肠癌的存在与否实现了选自 大于70％真阳性和小于30％真阴性、75％真阳性和小于25％真阴性、 85％真阳性和小于15％真阴性、90％真阳性和小于10％真阴性、95％ 真阳性和小于5％真阴性、或99％真阳性和小于1％真阴性的灵敏度和 特异性。
在本公开方法的一个方面，使用全部或一些生物标志物或生物 标志物的组合针对受试者的腺瘤性息肉或息肉样腺瘤的存在与否实 现了选自大于70％真阳性、75％真阳性、85％真阳性、90％真阳性、 95％真阳性或99％真阳性的灵敏度。在本公开方法的一个方面，使用 全部或一些生物标志物或生物标志物的组合针对受试者的腺瘤性息 肉或息肉样腺瘤的存在与否实现了选自大于70％真阴性、75％真阴性、 85％真阴性、90％真阴性、95％真阴性或99％真阴性的特异性。在本 公开方法的一个方面，通过附加试验如结肠镜检查、其他成像方法或 诊断试验或手术来确认腺瘤性息肉或息肉样腺瘤。在本公开方法的一 个方面，使用全部或一些生物标志物或生物标志物的组合针对受试者 的腺瘤性息肉或息肉样腺瘤的存在与否实现了选自大于70％真阳性 和小于30％真阴性、75％真阳性和小于25％真阴性、85％真阳性和小 于15％真阴性、90％真阳性和小于10％真阴性、95％真阳性和小于5％ 真阴性、或99％真阳性和小于1％真阴性的灵敏度和特异性。
在本公开方法的一个方面，使用全部或一些生物标志物或生物 标志物的组合针对受试者的有蒂息肉和无蒂息肉的存在与否实现了 选自大于70％真阳性、75％真阳性、85％真阳性、90％真阳性、95％ 真阳性或99％真阳性的灵敏度。在本公开方法的一个方面，使用全部 或一些生物标志物或生物标志物的组合针对受试者的有蒂息肉和无 蒂息肉的存在与否实现了选自大于70％真阴性、75％真阴性、85％真 阴性、90％真阴性、95％真阴性或99％真阴性的特异性。在本公开方 法的一个方面，通过附加试验如结肠镜检查、其他成像方法或诊断试 验或手术来确认有蒂息肉和无蒂息肉的存在与否。在本公开方法的一 个方面，使用全部或一些生物标志物或生物标志物的组合针对受试者 的有蒂息肉和无蒂息肉的存在与否实现了选自大于70％真阳性和小 于30％真阴性、75％真阳性和小于25％真阴性、85％真阳性和小于15％ 真阴性、90％真阳性和小于10％真阴性、95％真阳性和小于5％真阴性、 或99％真阳性和小于1％真阴性的灵敏度和特异性。
在本公开方法的一个方面，使用全部或一些生物标志物或生物 标志物的组合针对根据细胞发育异常或恶变前的程度表征的受试者 的腺瘤性息肉或息肉样腺瘤实现了选自大于70％真阳性、75％真阳性、 85％真阳性、90％真阳性、95％真阳性或99％真阳性的灵敏度。在本 公开方法的一个方面，使用全部或一些生物标志物或生物标志物的组 合针对根据细胞发育异常或恶变前的程度表征的受试者的腺瘤性息 肉或息肉样腺瘤实现了选自大于70％真阴性、75％真阴性、85％真阴 性、90％真阴性、95％真阴性或99％真阴性的特异性。在本公开方法 的一个方面，通过附加试验如结肠镜检查、其他成像方法或诊断试验 或手术来确认根据细胞发育异常或恶变前的程度表征的腺瘤性息肉 或息肉样腺瘤。在本公开方法的一个方面，使用全部或一些生物标志 物或生物标志物的组合针对根据细胞发育异常或恶变前的程度表征 的受试者的腺瘤性息肉或息肉样腺瘤实现了选自大于70％真阳性和 小于30％真阴性、75％真阳性和小于25％真阴性、85％真阳性和小于 15％真阴性、90％真阳性和小于10％真阴性、95％真阳性和小于5％真 阴性、或99％真阳性和小于1％真阴性的灵敏度和特异性。
VI.系统
本公开的系统和方法基于和/或通过使用一个或多个计算机处 理器系统而设计。本公开的计算机系统的实例在下文进行了描述。所 述计算机系统的变化形式是可能的，只要它们提供用于本公开的系统 和方法的平台。
本公开的计算机系统的一个实例显示于图13中。图13中显示 的计算机系统1300可被理解为可从介质1311和/或网络端口1305读 取指令的逻辑装置，该介质1311和/或网络端口1305可任选地连接到 具有固定介质1312的服务器1309。如在图13中所示的系统可包含 CPU 1301、磁盘驱动器1303、任选的输入设备(如键盘1315和/或鼠 标1316)以及任选的监视器1307。数据通信可通过通往在本地或远 程位置的服务器的指定通信介质来实现。通信介质可包括传送和/或接 收数据的任何手段。例如，通信介质可以是网络连接、无线连接或因 特网连接。这样的连接可提供在万维网上的通信。可以预想到，与本 公开相关的数据可以通过这样的网络或连接进行传送，以便由如图13 显示的主体1322接收和/或审查。
图14为显示了可以与本公开的示例性实施方案结合使用的计 算机系统1400的示例性架构的框图。如图14中所示，该示例性的计 算机系统可以包括用于处理指令的处理器1402。处理器的非限制性实 例包括：Intel XeonTM处理器、AMD OpteronTM处理器、Samsung32-bit RISC ARM 1176JZ(F)-S vl.OTM处理器、ARM Cortex-A8 Samsung S5PC100TM处理器、ARM Cortex-A8Apple A4TM处理器、 Marvell PXA 930TM处理器或功能上等同的处理器。多个执行线程可 用于并行处理。在本公开的一些方面，也可使用多个处理器或具有多个核的处理器，无论是在单个计算机系统中，在集群中，还是通过包 括多个计算机、蜂窝电话和/或个人数据助理设备的网络分布在整个系 统上。
如图14中所示，高速缓冲存储器1404可以连接到或并入处理 器1402以提供处理器1402最近或频繁使用的指令或数据的高速存储 器。处理器1402通过处理器总线1408连接到北桥1406。北桥1406 通过存储器总线1412连接到随机存取存储器(RAM)1410，并管理处理器1402对RAM 1410的访问。北桥1406还通过芯片组总线1416 连接到南桥1414。南桥1414又连接到外围总线1418。该外围总线可 以是，例如，PCI、PCI-X、PCI Express或其他外围总线。北桥和南 桥通常称作处理器芯片组，并管理处理器、RAM以及外围总线1418 上的外围组件之间的数据传输。在一些可替代的架构中，北桥的功能 可并入处理器中而不是使用单独的北桥芯片。在本公开的一些方面， 系统100可以包括连接到外围总线1418的加速器卡1422。该加速器 可以包括现场可编程门阵列(FPGA)或用于加速某种处理的其他硬件。例如，加速器可以用于自适应数据重组或用于评估在扩展集处理 中使用的代数表达式。
软件和数据存储在外部存储1424中并且可以加载到RAM 1410 和/或缓存1404中，以供处理器使用。系统1400包括用于管理系统资 源的操作系统；操作系统的非限制性实例包括：Linux、WindowsTM、MACOSTM、BlackBerry OSTM、iOSTM和其他功能等同的操作系统，以及在操作系统的顶端上运行的用于管理数据存储并根据本公开的 示例性实施方案进行优化的应用软件。
在这个实例中，系统1400还包括连接至外围总线的网络接口卡 (NIC)1420和1421，以用于向外部存储如网络附加存储(NAS)和 可用于分布式并行处理的其他计算机系统提供网络接口。
图15为示出了具有多个计算机系统1502a和1502b、多个蜂窝 电话和个人数字助理1502c以及网络附加存储(NAS)1504a和1504b 的网络1500的示意图。在示例性的实施方案中，系统1502a、1502b 和1502c可以管理数据存储并优化存储在网络附加存储(NAS)1504a 和1504b中的数据的数据存取。数学模型可用于该数据并使用跨计算 机系统1502a和1502b以及蜂窝电话和个人数字助理系统1502c的分 布式并行处理进行评价。计算机系统1502a和1502b以及蜂窝电话和 个人数字助理系统1502c也可提供用于存储在网络附加存储(NAS) 1504a和1504b中的数据的自适应数据重组的并行处理。很多种其他 计算机构架和系统可与本公开的各个实施方案结合使用。例如，刀片 式服务器可用于提供并行处理。处理器刀片可以通过底板连接，以提 供并行处理。存储也可通过单独的网络接口连接到底板或作为网络附 加存储(NAS)。
在一些示例性实施方案中，处理器可以保持独立的存储器空间， 并通过网络接口、底板或用于其他处理器进行并行处理的其他连接器 传送数据。在其他实施方案中，一些或所有处理器可使用共享的虚拟 地址存储空间。
图16为根据示例性实施方案的使用共享的虚拟地址存储空间 的多处理器计算机系统1600的框图。该系统包括可访问共享的存储 器子系统1604的多个处理器1602a-f。该系统在存储器子系统1604 中并入多个可编程硬件存储算法处理器(MAP)1606a-f。每个MAP1606a-f可包含存储器1608a-f以及一个或多个现场可编程门阵列 (FPGA)1610a-f。该MAP提供可配置功能单元，并且特定算法或算 法的一部分可提供给FPGA 1610a-f以用于密切配合相应的处理器进 行处理。例如，该MAP可用于评估关于数据模型的代数表达式并用 于进行示例性实施方案中的自适应数据重组。在该实例中，每个MAP 可由所有处理器进行全局访问以用于这些目的。在一种配置中，每个 MAP可以使用直接存储器存取(DMA)来访问相关联的存储器 1608a-f，从而允许它独立于相应的微处理器1602a-f且与相应的微处 理器1602a-f异步地执行任务。在该配置中，MAP可将结果直接馈送 至另一个MAP，以用于算法的流水线和并行执行。本公开预想计算 机可读存储介质，例如CD-ROM、存储键、闪存卡、软磁盘或其上存 储有程序的其他有形介质，其在计算环境中执行时，执行自定义算法 以实现如本公开方法所述的所提供的生物样品的预测可能性或评估 的全部或部分结果。在各个实施方案中，该计算机可读存储介质是非 暂时性的。
本公开的系统和方法整合了一个或多个实验室设备。
在一些实施方案中，该整合在实验室信息管理系统(LIMS)或 更低的水平下进行。计算机系统可以运行多个实验室设备。用于实验 室应用的软件和硬件可使用本公开的方法和系统进行整合。在各个实 施方案中，具有共有功能的相似组件在多个实验室设备中重复使用。
计算机系统可控制各个设备中的多个组件，从而创建可用组件 的新的组合。在另一实例中，本公开的计算机系统可通过控制该实验 室设备内的泵、传感器或其他组件来控制质谱法、板处理法、液相色 谱法。软件可由包括独立的实验室最终用户或任何其他合适的用户在 内的任何人提供。LIMS在整合实验室系统中的使用进一步描述于美 国专利申请7,991,560中，该专利申请通过引用以其整体并入本文。
在其中试剂盒提供计算机可读介质的方案中，它将包含用于执 行本公开的方法的完整程序。该程序包含用于收集、分析并生成输出 的程序指令，并且通常包含用于与本文所述的用户交互、处理该数据 以及分析信息并生成针对该用户独特的印刷或电子介质的计算机可 读代码和设备。
在其他方面，所述试剂盒提供了仅运行本公开方法的一部分的 有限的计算机可读介质。在这方面，该试剂盒提供了这样的程序，该 程序提供来自用户的数据输入并用于将用户输入(例如，经由因特网， 经由内部网等)的数据传送至在远程地点的计算环境如服务器(在其 上将进行本公开的自定义数学算法)。由用户提供的数据处理的处理 或完成在远程地点进行，并且该服务器也将用来生成报告。在审查报 告并完成提供完整报告所需的任何人工干预后，将完整的报告作为电 子报告或打印的报告传送回用户。
根据本公开的包含程序的存储介质可与用于程序安装和使用的 说明或可以从中获得这样的说明的网址一起包装。
VII.报告
当本公开的方法用于商业诊断目的，例如用于医疗领域中时， 通常将生成从该方法获得的信息的报告或汇总。
该方法的报告或汇总可包含关于一种或多种基因或蛋白质的表 达水平、息肉或肿瘤的分类、患者的风险水平(如高、中或低)、患 者的预后、治疗选择、治疗建议、生物标志物表达以及如何确定生物 标志物水平、生物标志物谱、临床和病理因素的信息和/或与患者疾病 状态相关的患者或群组的其他标准临床信息。
所述方法和报告可存储在数据库中。该方法可以在数据库中创 建受试者的记录并将数据填入该记录。该报告可以是纸质报告、音频 报告或电子记录。该报告可以显示和/或存储在计算设备(例如，手持 设备、台式计算机、智能设备、网站等)上。可以预期，报告将提供 给医师和/或患者。报告的接收可进一步包括建立与包含所述数据和报 告的服务器计算机的网络连接，并从该服务器计算机请求该数据和报 告。
在另一方面，本公开提供了生成包含关于从受试者获得的生物 样品的生物标志物信息的报告的方法，该方法包括以下步骤：确定样 品中以下一种或多种生物标志物或其结合配偶体之一的生物标志物 谱表达水平：SCDC26(CD26)、CEA分子5(CEACAM5)、CA195(CCR5)、CA19-9、M2PK(PKM2)、TIMP1、P-选择蛋白(SELPLG)、 VEGFA、HcGB(CGB)、绒毛蛋白、TATI(SPINK1)、A-L-岩藻糖苷 酶(FUCA2)、ANXA5、GAPDH、PKM2、ANXA4、GARS、RRBP1、 KRT8、SYNCRIP、S100A9、ANXA3、CAPG、HNRNPF、PPA1、 NME1、PSME3、AHCY、TPT1、HSPB1和RPSA和/或图9中的蛋 白质或它们的修饰形式，并创建汇总它们的表达水平的报告。在一些 方面，该报告可进一步包含将受试者分类成风险组，诸如“低风险”、 “中等风险”或“高风险”的分类。在各个实施方案中，包括上述蛋白质 中的两种、三种、四种、五种、六种、七种、八种、九种、十种、十 一种和全部十二种的群组。这样的群组可排除另外的蛋白质，或可以 进一步包含另外的蛋白质。
在所述方法的一个方面，如果确定了以下一种或多种生物标志 物或其结合配偶体之一的表达增加：SCDC26(CD26)、CEA分子5 (CEACAM5)、CA195(CCR5)、CA19-9、M2PK(PKM2)、TIMP1、P- 选择蛋白(SELPLG)、VEGFA、HcGB(CGB)、绒毛蛋白、TATI(SPINK1)、 A-L-岩藻糖苷酶(FUCA2)、ANXA5、GAPDH、PKM2、ANXA4、GARS、 RRBP1、KRT8、SYNCRIP、S100A9、ANXA3、CAPG、HNRNPF、 PPA1、NME1、PSME3、AHCY、TPT1、HSPB1和RPSA和/或图9 中的蛋白质或它们的修饰形式，则所述报告包含关于所述受试者具有 患有结肠息肉的增加的可能性的预测。在各个实施方案中，包括上述 蛋白质中的两种、三种、四种、五种、六种、七种、八种、九种、十 种、十一种和全部十二种的群组。这样的群组可排除另外的蛋白质， 或可以进一步包含另外的蛋白质。
在所述方法的另一方面，如果确定了以下一种或多种生物标志 物或其结合配偶体之一的表达增加：SCDC26(CD26)、CEA分子5 (CEACAM5)、CA195(CCR5)、CA19-9、M2PK(PKM2)、TIMP1、P- 选择蛋白(SELPLG)、VEGFA、HcGB(CGB)、绒毛蛋白、TATI(SPINK1)、 A-L-岩藻糖苷酶(FUCA2)、ANXA5、GAPDH、PKM2、ANXA4、GARS、 RRBP1、KRT8、SYNCRIP、S100A9、ANXA3、CAPG、HNRNPF、PPA1、NME1、PSME3、AHCY、TPT1、HSPB1和RPSA和/或图9 中的蛋白质或它们的修饰形式，则所述报告包含关于所述受试者具有 患有结肠息肉的降低的可能性的预测。在各个实施方案中，包括上述 蛋白质中的两种、三种、四种、五种、六种、七种、八种、九种、十 种、十一种和全部十二种的群组。这样的群组可排除另外的蛋白质， 或可以进一步包含另外的蛋白质。
在一个方面，该报告包括支持针对所述患者的治疗建议的信息。 例如，该信息可以包括定制诊断试验、结肠镜检查、手术、治疗性治 疗中的一个或多个以及不采取进一步的医疗行动的建议，此类治疗的 有益得分的可能性，或其他此类数据。在一些实施方案中，该报告进 一步包括对所述患者的治疗方式的建议。
在本公开的一个方面，所述报告是纸质形式。在本公开的一个 方面，所述报告是电子形式，如CD-ROM、闪存驱动器、本领域中已 知的其他电子存储设备。在本公开的另一方面，电子报告从有线或无 线网络下载到第二计算机设备，如膝上型计算机、移动电话或平板电 脑上。
在一个方面，所述报告指示，如果确定了以下一种或多种生物 标志物或其结合配偶体之一的表达增加：SCDC26(CD26)、CEA分子 5(CEACAM5)、CA195(CCR5)、CA19-9、M2PK(PKM2)、TIMP1、 P-选择蛋白(SELPLG)、VEGFA、HcGB(CGB)、绒毛蛋白、TATI (SPINK1)、A-L-岩藻糖苷酶(FUCA2)、ANXA5、GAPDH、PKM2、 ANXA4、GARS、RRBP1、KRT8、SYNCRIP、S100A9、ANXA3、 CAPG、HNRNPF、PPA1、NME1、PSME3、AHCY、TPT1、HSPB1 和RPSA和/或图9中的蛋白质或它们的修饰形式，则所述报告包含关 于所述受试者在5-10年具有结肠息肉或肿瘤复发的增加的可能性的 预测。在各个实施方案中，包括上述蛋白质中的两种、三种、四种、 五种、六种、七种、八种、九种、十种、十一种和全部十二种的群组。 这样的群组可排除另外的蛋白质，或可以进一步包含另外的蛋白质。
在另一方面，所述报告指示，如果确定了以下一种或多种生物 标志物或其结合配偶体之一的表达增加：SCDC26(CD26)、CEA分子 5(CEACAM5)、CA195(CCR5)、CA19-9、M2PK(PKM2)、TIMP1、 P-选择蛋白(SELPLG)、VEGFA、HcGB(CGB)、绒毛蛋白、TATI (SPINK1)、A-L-岩藻糖苷酶(FUCA2)、ANXA5、GAPDH、PKM2、 ANXA4、GARS、RRBP1、KRT8、SYNCRIP、S100A9、ANXA3、 CAPG、HNRNPF、PPA1、NME1、PSME3、AHCY、TPT1、HSPB1 和RPSA和/或图9中的蛋白质或它们的修饰形式，则所述报告包含关 于所述受试者在5-10年具有结肠息肉或肿瘤复发的降低的可能性的 预测。在各个实施方案中，包括上述蛋白质中的两种、三种、四种、 五种、六种、七种、八种、九种、十种、十一种和全部十二种的群组。 这样的群组可排除另外的蛋白质，或可以进一步包含另外的蛋白质。
在本公开的一些方面，所述报告进一步包括针对所述患者的结 肠疾病的治疗管理的治疗方式的建议。治疗管理选项可包括但不限于， 其他诊断试验，如结肠镜检查、可屈性乙状结肠镜检查(flex sigmoidscopy)、CT结肠成像术、粪便检验、排泄物检验、用治疗剂进一步治疗、手术干预以及不采取进一步行动。
本公开还提供了通过以下步骤制备针对患者的个人生物标志物 谱的方法：a)确定从受试者t获得的生物样品中以下至少一种或多种 的归一化表达水平：SCDC26(CD26)、CEA分子5(CEACAM5)、CA195 (CCR5)、CA19-9、M2PK(PKM2)、TIMP1、P-选择蛋白(SELPLG)、VEGFA、HcGB(CGB)、绒毛蛋白、TATI(SPINK1)、A-L-岩藻糖苷 酶(FUCA2)、ANXA5、GAPDH、PKM2、ANXA4、GARS、RRBP1、 KRT8、SYNCRIP、S100A9、ANXA3、CAPG、HNRNPF、PPA1、 NME1、PSME3、AHCY、TPT1、HSPB1和RPSA和/或图9中的蛋 白质或它们的修饰形式或其表达产物；以及(b)创建报告，该报告 汇总了通过基因表达分析获得的数据。在各个实施方案中，包括上述 蛋白质中的两种、三种、四种、五种、六种、七种、八种、九种、十 种、十一种和全部十二种的群组。这样的群组可排除另外的蛋白质， 或可以进一步包含另外的蛋白质。
VIII.试剂盒
用于本公开方法的材料适于根据公知的程序生产的试剂盒的制 备。本公开提供的试剂盒销售给医疗服务提供者，包括医师、临床实 验室科学家、护士、药剂师、处方人员(formulary official)或直接销 售给消费者。
试剂盒通常可包含插入材料、组合物、试剂、装置的组件以及 关于如何对特定的生物样品类型进行该方法或试验的说明。该试剂盒 可进一步包含能够通过各种测定类型(诸如ELISA测定、免疫测定、 蛋白质芯片或微阵列、DNA/RNA芯片或微阵列、RT-PCR、核酸测序、 质谱法、免疫组织化学法、流式细胞术或高含量细胞筛选)检测生物 标志物的试剂。
本公开提供了组合物，诸如能够与如本文所教导的生物标志物、 肽、多肽或蛋白质及其片段中的任意一种或多种特异性结合的结合剂。 结合剂可包括抗体、适体、光适体(photoaptamer)、蛋白质、肽、 肽模拟物或小分子。本公开提供的结合剂包括两种特异性结合剂，该 特异性结合剂通过与一种或多种期望的分子或分析物结合，诸如与感 兴趣的一种或多种蛋白质、多肽或肽或其片段结合(基本上排除随机 或不相关的其他分子，并且任选地基本排除结构相似或相关的其他分 子)而起作用。术语“特异性结合”并非必需要求结合剂排他地与其预 期的靶标结合。例如，如果在结合条件下，结合剂对预期的靶标的亲 和力是其对非靶标分子的亲和力的至少约2倍、优选至少约5倍、更 优选至少约10倍、更优选至少约25倍、更优选至少约50倍以及甚 至更优选至少约100倍或更多倍，则该结合剂可被称为与感兴趣的蛋 白质、多肽、肽和/或其片段特异性结合。
优选地，所述结合剂可以以此类结合的以下亲和常数(KA)与 其预期的靶标结合：KA 1x106M-1、更优选KA 1x107M-1、更优选KA 1x108M-1、甚至更优选KA 1x109M-1并且更优选KA1x1010M-1或KA 1x1011M-1，其中KA＝[SBA_T]/[SBA][1]，SBA表示特异性结合剂，T 表示预期的靶标。KA的确定可通过本领域中已知的方法进行，例如， 使用平衡透析和Scatchard作图分析。
在所述方法和试剂盒的一些应用中，结合剂将为免疫结合剂， 如抗体。可在本公开中使用的抗体的实例包括本领域中公知的多克隆 和单克隆抗体以及它们的片段。可在本公开的方法和试剂盒中使用的 抗体的另外的实例包括由至少两个完整的抗体形成的多价(例如，2 价、3价或更高价)和/或多特异性抗体(例如，双特异性或多特异性 抗体)，以及抗体片段(只要它们表现出期望的生物活性(特别是， 特异性结合感兴趣的抗原的能力))，以及这些片段的多价和/或多特 异性复合物。
抗体可以是IgA、IgD、IgE、IgG和IgM类中的任意类别，并 优选IgG类抗体。抗体可以是多克隆抗体，例如从其纯化的(例如， 亲和纯化的)抗血清或免疫球蛋白。抗体可以是单克隆抗体或单克隆 抗体的混合物。单克隆抗体可以以较高的选择性和重现性靶向抗原内 的特定抗原或特定表位。举例来说，但非限制性地，单克隆抗体可以 通过首先由Kohler等人1975(Nature 256:495)描述的杂交瘤方法来制 备，或者可以通过重组DNA方法(例如，在US 4,816,567中的)来 制备。例如，单克隆抗体还可以使用如Clackson等人1991(Nature352: 624-628)和Marks等人1991(J MolBiol 222:581-597)所述的技术从噬 菌体抗体文库中分离。
抗体结合剂可以是抗体片段。“抗体片段”包含完整抗体的一部 分，包括其抗原结合区或可变区。抗体片段的实例包括Fab、Fab'、 F(ab')2、Fv和scFv片段；双抗体；线性抗体；单链抗体分子；以及 由抗体片段形成的多价和/或多特异性抗体，例如双体、三体和多体。 上述称谓Fab、Fab'、F(ab')2、Fv、scFv等旨在具有其本领域确定的 含义。
制备多克隆和单克隆抗体以及它们的片段的方法是本领域公知 的，如用于制备重组抗体或其片段的方法(参见，例如，Harlow和 Lane,"Antibodies:A LaboratoryManual",Cold Spring Harbour Laboratory,New York,1988；Harlow和Lane,"UsingAntibodies:A Laboratory Manual",Cold Spring Harbour Laboratory,New York,1999,ISBN 0879695447；"Monoclonal Antibodies:A Manual of Techniques", Zola编著,CRCPress 1987,ISBN 0849364760；"Monoclonal Antibodies: A Practical Approach",Dean和Shepherd编著,Oxford University Press 2000,ISBN 0199637229；Methods inMolecular Biology,vol.248: "Antibody Engineering:Methods and Protocols",Lo编著,Humana Press 2004,ISBN 1588290921)。
本公开的抗体可来源于任何动物物种，优选脊椎动物物种，包 括，例如禽类和哺乳动物，或包含由其衍生的一个或多个部分。非限 制性地，抗体可以是鸡、鸡蛋、火鸡、鹅、鸭、珍珠鸡、鹌鹑或雉鸡 抗体。仍非限制性地，抗体可以是人、鼠(例如，小鼠、大鼠等)、 驴、兔、山羊、绵羊、豚鼠、骆驼(例如双峰骆驼(Camelus bactrianus) 和单峰骆驼(Camelusdromaderius))、美洲驼(例如，羊驼(Lama paccos)、大羊驼或骆马)或马抗体。
本公开还提供了针对本文提供的生物标志物的抗体，该抗体可 包含一个或多个氨基酸缺失、添加和/或置换(例如，保守置换)，只 要这样的改变保持其与相应抗原的结合。抗体还可以包含其组成氨基 酸残基的一个或多个天然或人工修饰(例如，糖基化等)。
本公开提供的抗体不限于通过包括免疫的方法产生的抗体，且 还包括被制备成包含至少一种能够与感兴趣抗原上的表位特异性结 合的互补性决定区(CDR)的任何多肽，例如重组表达的多肽。因此， 术语抗体或免疫结合剂适用于此类分子，而不论它们是在体外还是在 体内产生。
本公开试剂盒中的抗体或免疫结合剂、肽、多肽、蛋白质、生 物标志物等可以是各种形式，例如冻干的、在溶液中游离或固定在固 相上。抗体或免疫结合剂可以例如在多孔板中或作为阵列或微阵列来 提供，或者它们可以单独地和/或分别进行包装。它们可适当地标记以 进行检测，如本文所教导的。本文提供的试剂盒可以特别适于进行本 公开的测定方法，如免疫测定、ELISA测定、质谱测定、流式细胞术 等。
在本公开中提供了将由合格的临床科学家递送并使用的试剂盒。 在这样的试剂盒中，本公开提供了包含各种试剂的试剂盒，该试剂可 包括识别一种或多种所公开的生物标志物的抗体读出检测抗体，用于 量化一种或多种所公开的生物标志物的表达的基因特异性或基因选 择性探针和/或引物，用于预测结肠肿瘤状态或对治疗的反应的生物标 志物的修饰形式或结合配偶体。
试剂盒可以进一步包含容器(包括适用于所述方法的自动化实 现的微量滴定板)、预制的生物芯片、缓冲液、适当的试剂抗体、探 针、酶以进行测定。在本公开的一些方面，试剂盒可包含用于从生物 样品中提取蛋白质和核酸的试剂，和/或用于DNA或RNA扩增或蛋 白质分级分离或纯化的试剂，以及检测生物标志物的捕获生物芯片。 试剂盒中的试剂将具有与它们的使用或进行测定的步骤相关的标识 描述或标签或说明。此外，该试剂盒可进一步包含与它们在用于确定 结肠息肉/肿瘤状态和复发和治疗反应的可能性的方法中的使用相关 的说明，或者也可以组合提供计算机可读存储介质以确定结肠息肉/ 肿瘤状态和复发和治疗反应的可能性。
试剂盒可进一步包含用于数据分析的软件包，其可包含用于比 较的参考生物标志物谱。在一些应用中，试剂盒的软件包包含与中心 服务器的连接，以进行数据分析，并且其中包含具有对疾病状态的建 议、治疗建议或对用于疾病管理的治疗或程序的推荐的报告。
试剂盒中提供的报告可以是纸质或电子报告。它可以由试剂盒 中提供的计算机软件或者由计算机服务器来生成，其由用户上传至网 站，其中该计算机服务器生成该报告。
在本公开的一些方面，试剂盒可包含用于评估或量化作为试剂 盒的组件的预后、诊断、临床状态或预测信息的数学算法。在一些方 面，这将通过计算机可读存储介质递送，并且在本公开的其他方面， 这可以通过向用户提供访问包含运行数学算法的逻辑的计算机服务 器的密码来给出。
试剂盒可以以任何合适的方式进行包装，通常所有元件在单个 容器中，并随附用于执行该方法或试验的打印的说明书页。
在本公开中提供了将递送给医师的试剂盒。用于此目的的试剂 盒将包含供医师提供医疗信息的电子或书面文件，以及粘贴到含有生 物样品和任选的固定/防腐试剂的无菌容纳容器上的条形码标签。在一 些方面，这样的试剂盒将包含将通过邮件发送以供通过本文提供的方 法进行处理的邮寄说明和供给。
实施例
实施例1
结肠镜检查呈阴性诊断的个体的腺瘤或息肉状态的鉴定
通过使用经验证的生物标志物分类器，针对结肠息肉的存在与 否，检测来自基于结肠镜检查为腺瘤或息肉诊断阴性的患者的全血清 进行检测。独立地分析来自每个部位的样品的数据(即，验证数据集 不用于在发现交叉验证中的训练或测试)，并继而对结果间的重叠进 行评价。对表E1中的分类器的蛋白质和/或肽进行LC-MS/MS分析。
鉴定生物标志物。例如，生物标志物集示于表E1和表E2以及 图7中。
表E1
表E2
序号 名称(别名)
1 ANXA5 膜联蛋白A5
2 GAPDH 甘油醛-3-磷酸脱氢酶
3 PKM2 丙酮酸激酶同工酶M1/M2
4 ANXA4 膜联蛋白A4
5 GARS 甘氨酰-tRNA合成酶
6 RRBP1 核糖体结合蛋白1
7 KRT8 角蛋白II型细胞骨架8
8 SYNCRIP 核内不均一核糖核蛋白Q
9 S100A9 S100A9钙结合蛋白
10 ANXA3 膜联蛋白A3
11 CAPG 巨噬细胞加帽蛋白
12 HNRNPF 核内不均一核糖核蛋白F
13 PPA1 无机焦磷酸酶
14 NME1 核苷二磷酸激酶A
15 PSME3 蛋白酶体激活剂复合物亚基3
16 AHCY 腺苷高半胱氨酸酶
17 TPT1 翻译控制肿瘤蛋白
18 HSPB1 热休克蛋白β-1
19 RPSA 40S核糖体蛋白SA
将这些值与对照参考值进行比较。最后，将分类器谱与低或无 风险、中等风险和高风险的分类器谱进行比较，从而使患者样品以约 90％或更高的准确率与受试者的预测的腺瘤/息肉状态或正常状态相 关联。参见表E3。或者，通过免疫分析如免疫印迹、生物芯片、免 疫染色和/或流式细胞术分析使用生物标志物分类器进行临床检测。
表E3
实施例2
先前具有结肠息肉的个体的息肉状态复发的鉴定
使用具有特异性结合或识别针对表E1和/或表E2中的蛋白质生 物标志物分类器的抗原的抗体的捕获生物芯片以及对照参考对来自 早先具有结肠息肉肿瘤的患者的全血清样品中的抗原进行谱分析。
筛选样品，以确定患者是否具有结肠息肉或息肉的复发。芯片 与样品在室温下一起孵育，以使抗体与样品中的抗原形成复合物。接 着，用温和的去污剂溶液洗涤芯片，以去除未特异性结合的任何蛋白 质或抗体。添加第二抗体与检测试剂的复合物且使其结合该芯片，并 用温和的洗涤剂进行洗涤。使用阅读器如CCD相机对蛋白质进行定 量。最后，将来自生物芯片读出的分类器谱与低或无风险、中等风险 和高风险复发分类器的谱进行比较，以确定患者的复发状态。
实施例3A
在本研究中，从即将接受结肠镜检查的患者中采集血液。使用 基于串联质谱法的方法采集关于血浆中存在的基于蛋白质的分子特 征的谱的定量数据，并且使用该数据来鉴定特征，该特征包含能够预 测结肠镜检查程序的结果的分类器。
研究设计和患者样品采集
为了将血浆蛋白质谱与患者结肠镜检查结果相关联，在他们进 行结肠镜检查的当天，从进行结肠镜检查的患者中采集血液样品。入 选标准要求患者等于或大于18岁，且愿意并能够签署知情同意书。 这是一个“全体愿意参加者(all comers)”研究，其中患者可能经受根 据所建议的常规筛查、因先前个人或家族病史而采取的预防措施或对 个人健康症状的随访的程序。
在结肠镜检查的常规准备(包含过夜禁食、液体型限制以及去 除粪便物质的肠道准备)后，将血液样品吸至包含作为抗凝剂的EDTA 的血浆采集设备。根据制造商的说明，将血液样品混合、离心以分离 血浆，并在四小时内收集分离的血浆并将其在-80℃下冷冻。
除了血浆样品之外，还收集患者临床数据如年龄、体重、性别、 种族、当前的用药和指征以及个人和家族健康史，如同针对任何采集 和检查的组织的结肠镜检查程序报告和病理学报告。收集了超过500 名患者的样品。在表E4、表E5和表E6中提供了患者人口统计数据。
表E4
表E5
p值来自相关性的卡方检验
表E6
用于血浆蛋白质分析的样品制备
选择152个样品(76个息肉和/或腺瘤和76个对照)用于分类 器分析。患者的息肉和/或腺瘤组随机地选自较大的研究组且与对照在 年龄和性别上相匹配。制备患者的血浆蛋白质样品用于如下的LCMS 测量。将血浆样品从-80℃的存储中解冻并通过过滤器离心去除脂质和 颗粒。通过基于免疫亲和柱的消耗去除滤出的血浆中的高丰度蛋白质。 通过反相HPLC将较低丰度的流过蛋白质分离成级分。将所选择的蛋 白质级分(每个样品6份)通过胰蛋白酶-TFE消化还原成肽，并使 所得肽再悬浮于乙腈/甲酸LCMS上样缓冲液中。
LCMS数据采集和蛋白质分子特征量化
将来自每个患者的血浆样品的若干级分的再悬浮的肽通过 UHPLC注射至串联质谱仪(Q-TOF)用于定量分析。分析收集的数据 (保留时间、质/荷比和离子丰度)以检测观察到的被称为分子特征的 峰。三维峰积分算法决定了该分子特征的相对丰度。
在使用三次样条算法进行数据集叠加和校准之后比较来自多个 患者样品的分子特征数据。仅被确定为以50％或更高的百分比存在于 至少一个患者类别(无或有息肉/腺瘤)中的特征被考虑用于进一步的 分析。在该集中缺少患者特征数据的情况下，通过对如在其他样品中 观察到的先验峰位置上的原始离子丰度数据进行积分来估算特征值。 来自152个患者样品中的每个样品的大于145,000个分子特征包含用 于随后的分类器分析的最终数据集。
数据归一化、特征选择和分类器组装
将来源于单个原始中性质量的不同分子特征的定量数据组合并 汇总。例如，来自同一母体分子的+2m/z和+3m/z特征通过合并成单 个中性质量簇(NMC)值而进行组合。
通过在相同的研究日期以及同一仪器上收集的样品的平均值调 节NMC对来自不同样品的分子特征数据进行归一化。平衡数据采集 以使得在每个仪器-日期组中评价近似相等数目的无和有息肉/腺瘤样 品。这种方法被定义为簇-仪器-日期(“CID”)归一化。
数据的初始分析表明，女性样品的激素替代疗法状态的不平衡 可能是分类器构建中的混杂因素。为了消除这种可能性，将表明与 HRT相关的分子特征通过不同的分类器组装进行鉴定并从随后的分 析中去除。
仅具有来自所有实验级分的完整数据的样品用于分析。在最初 测量的152个样品中，保留108个完整的样品。对于大多数排除的样 品，6个样品级分中的一个或多个的QC失败导致被排除。
使用最终的归一化数据，创建分类器并对它们从息肉和/或腺瘤 样品中鉴别无息肉和腺瘤的患者样品的能力进行评估。在样品数据的 五十个70/30训练/测试分割(splits)中的每一个中，使用弹性网络方 法进行特征选择，从而将所考虑的NMC的数目从多于100,000个减 少至约200-250个。然后，使用这些选定的NMC来构建基于SVM(乙 状结肠-核)的分类器。在五十个训练/测试分割的每次迭代中，确定 如通过ROC图上的AUC测量的测试数据(灵敏度和特异性的组合测 量)的分类器的性能。所得的平均AUC(0.79+/-0.08)示于图1A中。 根据二等分该图的虚线，该AUC明显不同于0.5——不能达到鉴别能 力的随机测定的值。因此，图1A提供了测试集性能的比较。X轴表 示假阳性率。Y轴表示真阳性率。
为了确认弹性网络/SVM分类器性能的稳健性，对类别分配， 即息肉/腺瘤相比无息肉/腺瘤进行随机排列，并在整个五十次迭代中 再次进行整个特征选择和分类器组装过程。所得平均AUC (0.52+/-0.09)示于图2A中，且表明诸如正确分配确定的结果不太 可能偶然出现。因此，图2A提供了测试集性能的验证。X轴表示假 阳性率。Y轴表示真阳性率。
结果的显著性的另外的测量是单个NMC在五十个70/30训练/ 测试分割分类器中出现的频率的列表。在每一次迭代中，为分类器选 择约200-250个特征；特征在50次迭代中出现至少3次或更多次是 非偶然预期的结果。特征频率表的帕累托图(排序的直方图)示于图 3中。该数据指示大量特征被多次选择，从而表明它们参与鉴别分类 器的稳健性。当选择频率最高的特征(即，不同相关组中的前30个) 并将其用于在嵌套的70(70/30)/30分析结构中构建分类器时，所得平 均AUC仍然明显不同于随机的。该结果指示存在可由选定的特征集 构建的多个分类器。
分类器分子特征的子集
通过外循环/内循环策略来鉴定分类器特征的较小子集。在该方 法中，样品分成50个外循环70/30分割和500个内循环70/30分割。 进行多个内循环用于特征选择，计算SVM分类器内部测试的ROC AUC，并且选择500次迭代中最好的5％并保留所包含的特征。使用弹性网络选择最终的一组特征，以构建外循环SVM分类器。对于不 同大小的分类器，使用来自选定的内循环的特征的频率等级来确定特 征的优先顺序(例如，频率最高的10、20、30个等)。基于外循环 测试集评估所得分类器，且测量性能AUC。图5示出了50次外循环 迭代的平均ROC，且表明大小为30的分类器保留了显著的预测值 (AUC＝0.645+/-0.092)。在图5中，Y轴显示真阳性率而X轴显示 假阳性率。由于确认该结果不能偶然得到，因此对50个不同的样品 集(其中样品类别分配已随机重新分配)执行该程序。所得AUC (0.502+/-0.101，如图6中所示)是随机的，从而确认了正确的类别 分配结果的稳健性。在图6中，Y轴显示真阳性率而X轴显示假阳性 率。表E7表明已用大小为10个特征或NMC的分类器证明了显著性能的类似迹象。
表E7
大小 AUC sd
100 0.70 0.08
50 0.66 0.09
40 0.65 0.09
30 0.64 0.09
20 0.63 0.09
10 0.60 0.09
分类器分子特征的鉴定
通过质谱法进行的分子特征的质量测定足够准确和精确地提供 唯一的鉴定。在本实施例中组装的分类器中表示的1014个特征(每 个特征出现3次或更多次)的质量在如图7的附表中列出。准确的质 量对于分子特征是固有唯一地鉴定性的，因此可以确定这些特征的一 级氨基酸序列和任何翻译后修饰以便将它们的测量值转化为可替代 的表示。
实施例3B
研究设计对应于实施例3A的研究设计，并具有以下附加细节。
LCMS数据采集和蛋白质分子特征量化
经由UHPLC将来自每个患者的血浆样品的若干级分的再悬浮 的肽注射至串联质谱仪(Q-TOF)，以用于定量分析。对收集的数据 (保留时间、质/荷比和离子丰度)进行分析，以检测所观察到的被称 为分子特征的峰。三维峰积分算法确定了分子特征的相对丰度。平均 来说，从每个血浆样品中检测并定量出约364,000个分子特征。
在使用三次样条算法进行数据集叠加和校准之后比较来自多个 患者样品的分子特征数据。仅被确定为以50％或更高的百分比存在于 至少一个患者类别(无或有息肉/腺瘤)中的特征被考虑用于进一步的 分析。在该集中缺失患者特征数据的情况下，通过对如在其他样品中 观察到的先验峰位置上的原始离子丰度数据进行积分来估算特征值。 来自152个患者样品中的每个样品的约149,000个分子特征包含用于 随后的分类器分析的最终数据集。
数据归一化、特征选择和分类器组装
将来源于单个原始中性质量的不同分子特征的定量数据组合并 汇总。例如，来自同一母体分子的+2m/z和+3m/z特征通过合并成单 个中性质量簇(NMC)值而进行组合。NMC的总数目为约105,000 个。
细节如实施例3A中所述。此外，通过用于指示较高鉴定概率 的参数对特征进行过滤；例如，仅考虑电荷状态大于1(z>1)的特征。 这将用于分类器分析的NMC的总数目减少至约47,000个。
进一步参考对实施例3A的分析，在该分析中，使用十轮10折 交叉验证来选择特征并构建分类器。在每一轮中，90％的数据用于使 用弹性网络回归算法来选择特征，基于所确定的特征系数的排序来选 择前20个特征，并随后构建具有线性核的SVM分类器。然后，基于 所给倍数的测试集中提供的10％的样品对这个最终的分类器进行评 估。因此，在每一轮的10折交叉验证中，每一个样品在测试集中仅 出现一次。使用来自每一个样品的分类器的预测测试集值来构建该轮 的ROC图，其中每个样品一个点。对十个ROC图(每一轮一个)进行平均化并绘图。针对分析中使用的108个完整的样品，以及通过使 用原始结肠镜检查确定的诊断作为比较物，得到20个特征分类器的 中值AUC为0.91。平均AUC为0.91±0.021。图1B。
为了确认分类器性能的稳健性，对类别分配，即息肉/腺瘤相比 无息肉/腺瘤进行随机排列，并在整个十轮的10折交叉验证中再次进 行整个特征选择和分类器组装过程，如本文所述。中值AUC(0.52) 和平均AUC(0.52±0.033)(图2B)表明诸如正确分配确定的结果(AUC 0.91)不大可能偶然出现。
结果的显著性的另外的测量是单个NMC在十轮的10折交叉验 证中创建的100个分类器中出现的频率的列表。在每一次迭代中，选 择20个特征用于分类器；特征在多个分类器中的出现指示特征选择 和分类器过程的稳健性。通过使用原始诊断构建分类器(如在图1B 中观察到的)，多数特征被选择了不止一次。最频繁被选的特征从100 个分类器中的99个中选择。参见图4。相比之下，通过使用随机特征 选择，最频繁被选的特征仅被选择了三次。总之，206个特征在100 个20特征分类器中的一个或多个中出现。
分类器分子特征的鉴定
通过质谱法进行的分子特征的质量测定足够准确和精确地提供 唯一的鉴定。在本实施例中组装的分类器中表示的206个特征的质量 在如图8的附表中列出。准确的质量对于分子特征是固有唯一地鉴定 性的，因此可以确定这些特征的一级氨基酸序列和任何翻译后修饰以 便将它们的测量值转化为可替代的表示。
实施例4
MRM测定发展
最初，对先前报道为与结肠直肠癌具有关联的188种蛋白质在 计算机上进行查询以揭示用于靶向蛋白质组谱分析的潜在肽候选物。 从成千上万个潜在的胰蛋白酶肽中，选择初步的一组1056个用于实 验验证。从实验验证中选择最终一组337个肽(代表187种蛋白质)， 以包含最终的多反应监测(MRM)试验。此外，将用重(全部为C13) 精氨酸(R)或赖氨酸(K)标记的具有确切序列组成的337个补充 肽作为内标物而并入，以在最终分析中用作归一化参考。
用于血浆蛋白质分析的样品制备
根据两种方法(称为稀释和消耗)制备用于MRM LCMS测量 的患者血浆蛋白质样品。
在稀释方法中，将血浆样品从-80℃存储中解冻并通过过滤器离 心去除脂质和颗粒。将剩余的蛋白质通过胰蛋白酶-TFE消化还原成 肽，并使所得肽再悬浮于乙腈/甲酸MRMLCMS上样缓冲液中。
在消耗方法中，将血浆样品从-80℃存储中解冻并通过过滤器离 心去除脂质和颗粒。通过基于免疫亲和柱的消耗去除滤出的血浆中的 高丰度蛋白质。将较低丰度的流过蛋白质用胰蛋白酶-TFE消化还原 成肽，并使所得肽再悬浮于乙腈/甲酸MRM LCMS上样缓冲液中。
LCMS数据采集和过渡特征量化
经由UHPLC将来自每个患者的血浆样品的再悬浮的肽注射至 三重四极杆质谱仪(QQQ)，以用于定量分析。对收集的数据(保留 时间、前体质量、碎片质量和离子丰度)进行分析，以检测所观察到 的被称为过渡的峰。
采用二维峰积分算法来确定每个过渡峰的曲线下面积(AUC)。
将用重(全部为C13)精氨酸(R)或赖氨酸(K)标记的具有 确切序列组成的补充肽用作676个靶向过渡中的每一个的内标物。采 用补充的内标AUC值对过渡AUC值进行归一化，以得到每个过渡的 浓度值。
数据归一化、特征选择和分类器组装
对于分类器组装和性能评估，基于原始肽峰面积与相关联的标 记的标准肽原始峰面积的比值来使用特征浓度值。不对其原始峰面积 应用归一化。将过渡的缺失值设置为0。
使用10×10折交叉验证过程来评估分类器模型和相关的分类性 能。在该过程中，首先应用特征选择来减少所使用的特征的数目，接 着是分类器模型的开发以及随后的分类性能评估。对于每轮10折交 叉验证，将数据分成10个分割份，每个包含90％的样品作为训练集 而剩余10％的样品作为测试集。在该过程中，总共95个样品中的每 一个在测试集中评估一次。仅使用训练集进行特征选择和模型组装过 程，并且随后将这些模型应用于测试集以评估分类器性能。
为了进一步评估分类性能的概括，将该整个10折交叉验证程序 重复10次，每次具有训练集和测试集的不同取样。
用于分类器分析的过渡特征的总数目为674。为了探索具有较 少数目的特征的分类性能，在构建分类模型之前应用弹性网络特征选 择。在该过程中，构建了弹性网络模型并在分类模型的开发中使用给 出20个过渡特征的模型。由于交叉-折回验证过程的每一折具有它自 己的特征选择步骤，因此每一折可选择不同的特征，从而在整个10×10 折交叉验证过程的模型中使用的特征的总数目将大于或等于20。
在特征选择步骤之后，使用具有线性核的支持向量机(SVM) 算法构建分类器模型。在构建训练集的分类器模型后，将其在未经修 改的情况下直接应用于测试集，并且产生相关的受试者工作特征 (ROC)曲线，从该曲线计算曲线下面积(AUC)。在10×10折交叉验证过程中，得到平均测试集AUC(0.76+/-0.035)，图10指示了 分类模型鉴别结肠直肠癌和正常患者样品的能力。为了进一步评估特 征选择过程中选定的特征，提供了频率/等级图(图11)。该图显示 了若干特征，这些特征在全部或几乎全部的交叉验证折中被选定，突出了它们区分结肠直肠癌与正常样品的效用。通过分类过程鉴定的特 征的列表在图12中列出。
研究设计和患者样品采集
对照 CRC疾病
女性 24 23
男性 24 24
p＝1
年龄 65.0+/-9.7 65.5+/-9.6
(平均值+/-标准差，岁)
p＝0.82
尽管本文中已经示出并描述了本公开的优选实施方案，但对本 领域技术人员显而易见的是这样的实施方案仅通过示例的方式提供。 本领域技术人员在不脱离本公开的情况下现将想到许多变化、改变和 替换。应当理解，本文所述的本公开实施方案的各种替代方案均可用 于实施本公开。其意图在于以下述权利要求限定本公开的范围并由此 涵盖这些权利要求范围内的方法和结构及其等同物。
序列表
<110> 迪森德克斯公司
<120> 用于评估结肠肿瘤的存在或风险的方法
<130> 36765-703.201
<140>
<141>
<150> 61/772,979
<151> 2013-03-05
<150> 61/732,024
<151> 2012-11-30
<160> 188
<170> PatentIn version 3.5
<210> 1
<211> 375
<212> PRT
<213> 智人
<400> 1
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Ser Ile Val Gly Arg Pro Arg His Gln Gly Val Met Val Gly Met Gly
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Gln Lys Asp Ser Tyr Val Gly Asp Glu Ala Gln Ser Lys Arg Gly Ile
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Leu Thr Leu Lys Tyr Pro Ile Glu His Gly Ile Val Thr Asn Trp Asp
65 70 75 80
Asp Met Glu Lys Ile Trp His His Thr Phe Tyr Asn Glu Leu Arg Val
85 90 95
Ala Pro Glu Glu His Pro Val Leu Leu Thr Glu Ala Pro Leu Asn Pro
100 105 110
Lys Ala Asn Arg Glu Lys Met Thr Gln Ile Met Phe Glu Thr Phe Asn
115 120 125
Thr Pro Ala Met Tyr Val Ala Ile Gln Ala Val Leu Ser Leu Tyr Ala
130 135 140
Ser Gly Arg Thr Thr Gly Ile Val Met Asp Ser Gly Asp Gly Val Thr
145 150 155 160
His Thr Val Pro Ile Tyr Glu Gly Tyr Ala Leu Pro His Ala Ile Leu
165 170 175
Arg Leu Asp Leu Ala Gly Arg Asp Leu Thr Asp Tyr Leu Met Lys Ile
180 185 190
Leu Thr Glu Arg Gly Tyr Ser Phe Thr Thr Thr Ala Glu Arg Glu Ile
195 200 205
Val Arg Asp Ile Lys Glu Lys Leu Cys Tyr Val Ala Leu Asp Phe Glu
210 215 220
Gln Glu Met Ala Thr Ala Ala Ser Ser Ser Ser Leu Glu Lys Ser Tyr
225 230 235 240
Glu Leu Pro Asp Gly Gln Val Ile Thr Ile Gly Asn Glu Arg Phe Arg
245 250 255
Cys Pro Glu Ala Leu Phe Gln Pro Ser Phe Leu Gly Met Glu Ser Cys
260 265 270
Gly Ile His Glu Thr Thr Phe Asn Ser Ile Met Lys Cys Asp Val Asp
275 280 285
Ile Arg Lys Asp Leu Tyr Ala Asn Thr Val Leu Ser Gly Gly Thr Thr
290 295 300
Met Tyr Pro Gly Ile Ala Asp Arg Met Gln Lys Glu Ile Thr Ala Leu
305 310 315 320
Ala Pro Ser Thr Met Lys Ile Lys Ile Ile Ala Pro Pro Glu Arg Lys
325 330 335
Tyr Ser Val Trp Ile Gly Gly Ser Ile Leu Ala Ser Leu Ser Thr Phe
340 345 350
Gln Gln Met Trp Ile Ser Lys Gln Glu Tyr Asp Glu Ser Gly Pro Ser
355 360 365
Ile Val His Arg Lys Cys Phe
370 375
<210> 2
<211> 376
<212> PRT
<213> 智人
<400> 2
Met Cys Glu Glu Glu Thr Thr Ala Leu Val Cys Asp Asn Gly Ser Gly
1 5 10 15
Leu Cys Lys Ala Gly Phe Ala Gly Asp Asp Ala Pro Arg Ala Val Phe
20 25 30
Pro Ser Ile Val Gly Arg Pro Arg His Gln Gly Val Met Val Gly Met
35 40 45
Gly Gln Lys Asp Ser Tyr Val Gly Asp Glu Ala Gln Ser Lys Arg Gly
50 55 60
Ile Leu Thr Leu Lys Tyr Pro Ile Glu His Gly Ile Ile Thr Asn Trp
65 70 75 80
Asp Asp Met Glu Lys Ile Trp His His Ser Phe Tyr Asn Glu Leu Arg
85 90 95
Val Ala Pro Glu Glu His Pro Thr Leu Leu Thr Glu Ala Pro Leu Asn
100 105 110
Pro Lys Ala Asn Arg Glu Lys Met Thr Gln Ile Met Phe Glu Thr Phe
115 120 125
Asn Val Pro Ala Met Tyr Val Ala Ile Gln Ala Val Leu Ser Leu Tyr
130 135 140
Ala Ser Gly Arg Thr Thr Gly Ile Val Leu Asp Ser Gly Asp Gly Val
145 150 155 160
Thr His Asn Val Pro Ile Tyr Glu Gly Tyr Ala Leu Pro His Ala Ile
165 170 175
Met Arg Leu Asp Leu Ala Gly Arg Asp Leu Thr Asp Tyr Leu Met Lys
180 185 190
Ile Leu Thr Glu Arg Gly Tyr Ser Phe Val Thr Thr Ala Glu Arg Glu
195 200 205
Ile Val Arg Asp Ile Lys Glu Lys Leu Cys Tyr Val Ala Leu Asp Phe
210 215 220
Glu Asn Glu Met Ala Thr Ala Ala Ser Ser Ser Ser Leu Glu Lys Ser
225 230 235 240
Tyr Glu Leu Pro Asp Gly Gln Val Ile Thr Ile Gly Asn Glu Arg Phe
245 250 255
Arg Cys Pro Glu Thr Leu Phe Gln Pro Ser Phe Ile Gly Met Glu Ser
260 265 270
Ala Gly Ile His Glu Thr Thr Tyr Asn Ser Ile Met Lys Cys Asp Ile
275 280 285
Asp Ile Arg Lys Asp Leu Tyr Ala Asn Asn Val Leu Ser Gly Gly Thr
290 295 300
Thr Met Tyr Pro Gly Ile Ala Asp Arg Met Gln Lys Glu Ile Thr Ala
305 310 315 320
Leu Ala Pro Ser Thr Met Lys Ile Lys Ile Ile Ala Pro Pro Glu Arg
325 330 335
Lys Tyr Ser Val Trp Ile Gly Gly Ser Ile Leu Ala Ser Leu Ser Thr
340 345 350
Phe Gln Gln Met Trp Ile Ser Lys Pro Glu Tyr Asp Glu Ala Gly Pro
355 360 365
Ser Ile Val His Arg Lys Cys Phe
370 375
<210> 3
<211> 485
<212> PRT
<213> 智人
<400> 3
Met Arg Lys Arg Ala Pro Gln Ser Glu Met Ala Pro Ala Gly Val Ser
1 5 10 15
Leu Arg Ala Thr Ile Leu Cys Leu Leu Ala Trp Ala Gly Leu Ala Ala
20 25 30
Gly Asp Arg Val Tyr Ile His Pro Phe His Leu Val Ile His Asn Glu
35 40 45
Ser Thr Cys Glu Gln Leu Ala Lys Ala Asn Ala Gly Lys Pro Lys Asp
50 55 60
Pro Thr Phe Ile Pro Ala Pro Ile Gln Ala Lys Thr Ser Pro Val Asp
65 70 75 80
Glu Lys Ala Leu Gln Asp Gln Leu Val Leu Val Ala Ala Lys Leu Asp
85 90 95
Thr Glu Asp Lys Leu Arg Ala Ala Met Val Gly Met Leu Ala Asn Phe
100 105 110
Leu Gly Phe Arg Ile Tyr Gly Met His Ser Glu Leu Trp Gly Val Val
115 120 125
His Gly Ala Thr Val Leu Ser Pro Thr Ala Val Phe Gly Thr Leu Ala
130 135 140
Ser Leu Tyr Leu Gly Ala Leu Asp His Thr Ala Asp Arg Leu Gln Ala
145 150 155 160
Ile Leu Gly Val Pro Trp Lys Asp Lys Asn Cys Thr Ser Arg Leu Asp
165 170 175
Ala His Lys Val Leu Ser Ala Leu Gln Ala Val Gln Gly Leu Leu Val
180 185 190
Ala Gln Gly Arg Ala Asp Ser Gln Ala Gln Leu Leu Leu Ser Thr Val
195 200 205
Val Gly Val Phe Thr Ala Pro Gly Leu His Leu Lys Gln Pro Phe Val
210 215 220
Gln Gly Leu Ala Leu Tyr Thr Pro Val Val Leu Pro Arg Ser Leu Asp
225 230 235 240
Phe Thr Glu Leu Asp Val Ala Ala Glu Lys Ile Asp Arg Phe Met Gln
245 250 255
Ala Val Thr Gly Trp Lys Thr Gly Cys Ser Leu Met Gly Ala Ser Val
260 265 270
Asp Ser Thr Leu Ala Phe Asn Thr Tyr Val His Phe Gln Gly Lys Met
275 280 285
Lys Gly Phe Ser Leu Leu Ala Glu Pro Gln Glu Phe Trp Val Asp Asn
290 295 300
Ser Thr Ser Val Ser Val Pro Met Leu Ser Gly Met Gly Thr Phe Gln
305 310 315 320
His Trp Ser Asp Ile Gln Asp Asn Phe Ser Val Thr Gln Val Pro Phe
325 330 335
Thr Glu Ser Ala Cys Leu Leu Leu Ile Gln Pro His Tyr Ala Ser Asp
340 345 350
Leu Asp Lys Val Glu Gly Leu Thr Phe Gln Gln Asn Ser Leu Asn Trp
355 360 365
Met Lys Lys Leu Ser Pro Arg Thr Ile His Leu Thr Met Pro Gln Leu
370 375 380
Val Leu Gln Gly Ser Tyr Asp Leu Gln Asp Leu Leu Ala Gln Ala Glu
385 390 395 400
Leu Pro Ala Ile Leu His Thr Glu Leu Asn Leu Gln Lys Leu Ser Asn
405 410 415
Asp Arg Ile Arg Val Gly Glu Val Leu Asn Ser Ile Phe Phe Glu Leu
420 425 430
Glu Ala Asp Glu Arg Glu Pro Thr Glu Ser Thr Gln Gln Leu Asn Lys
435 440 445
Pro Glu Val Leu Glu Val Thr Leu Asn Arg Pro Phe Leu Phe Ala Val
450 455 460
Tyr Asp Gln Ser Ala Thr Ala Leu His Phe Leu Gly Arg Val Ala Asn
465 470 475 480
Pro Leu Ser Thr Ala
485
<210> 4
<211> 432
<212> PRT
<213> 智人
<400> 4
Met Ser Asp Lys Leu Pro Tyr Lys Val Ala Asp Ile Gly Leu Ala Ala
1 5 10 15
Trp Gly Arg Lys Ala Leu Asp Ile Ala Glu Asn Glu Met Pro Gly Leu
20 25 30
Met Arg Met Arg Glu Arg Tyr Ser Ala Ser Lys Pro Leu Lys Gly Ala
35 40 45
Arg Ile Ala Gly Cys Leu His Met Thr Val Glu Thr Ala Val Leu Ile
50 55 60
Glu Thr Leu Val Thr Leu Gly Ala Glu Val Gln Trp Ser Ser Cys Asn
65 70 75 80
Ile Phe Ser Thr Gln Asp His Ala Ala Ala Ala Ile Ala Lys Ala Gly
85 90 95
Ile Pro Val Tyr Ala Trp Lys Gly Glu Thr Asp Glu Glu Tyr Leu Trp
100 105 110
Cys Ile Glu Gln Thr Leu Tyr Phe Lys Asp Gly Pro Leu Asn Met Ile
115 120 125
Leu Asp Asp Gly Gly Asp Leu Thr Asn Leu Ile His Thr Lys Tyr Pro
130 135 140
Gln Leu Leu Pro Gly Ile Arg Gly Ile Ser Glu Glu Thr Thr Thr Gly
145 150 155 160
Val His Asn Leu Tyr Lys Met Met Ala Asn Gly Ile Leu Lys Val Pro
165 170 175
Ala Ile Asn Val Asn Asp Ser Val Thr Lys Ser Lys Phe Asp Asn Leu
180 185 190
Tyr Gly Cys Arg Glu Ser Leu Ile Asp Gly Ile Lys Arg Ala Thr Asp
195 200 205
Val Met Ile Ala Gly Lys Val Ala Val Val Ala Gly Tyr Gly Asp Val
210 215 220
Gly Lys Gly Cys Ala Gln Ala Leu Arg Gly Phe Gly Ala Arg Val Ile
225 230 235 240
Ile Thr Glu Ile Asp Pro Ile Asn Ala Leu Gln Ala Ala Met Glu Gly
245 250 255
Tyr Glu Val Thr Thr Met Asp Glu Ala Cys Gln Glu Gly Asn Ile Phe
260 265 270
Val Thr Thr Thr Gly Cys Ile Asp Ile Ile Leu Gly Arg His Phe Glu
275 280 285
Gln Met Lys Asp Asp Ala Ile Val Cys Asn Ile Gly His Phe Asp Val
290 295 300
Glu Ile Asp Val Lys Trp Leu Asn Glu Asn Ala Val Glu Lys Val Asn
305 310 315 320
Ile Lys Pro Gln Val Asp Arg Tyr Arg Leu Lys Asn Gly Arg Arg Ile
325 330 335
Ile Leu Leu Ala Glu Gly Arg Leu Val Asn Leu Gly Cys Ala Met Gly
340 345 350
His Pro Ser Phe Val Met Ser Asn Ser Phe Thr Asn Gln Val Met Ala
355 360 365
Gln Ile Glu Leu Trp Thr His Pro Asp Lys Tyr Pro Val Gly Val His
370 375 380
Phe Leu Pro Lys Lys Leu Asp Glu Ala Val Ala Glu Ala His Leu Gly
385 390 395 400
Lys Leu Asn Val Lys Leu Thr Lys Leu Thr Glu Lys Gln Ala Gln Tyr
405 410 415
Leu Gly Met Ser Cys Asp Gly Pro Phe Lys Pro Asp His Tyr Arg Tyr
420 425 430
<210> 5
<211> 316
<212> PRT
<213> 智人
<400> 5
Met Ala Ser Arg Leu Leu Leu Asn Asn Gly Ala Lys Met Pro Ile Leu
1 5 10 15
Gly Leu Gly Thr Trp Lys Ser Pro Pro Gly Gln Val Thr Glu Ala Val
20 25 30
Lys Val Ala Ile Asp Val Gly Tyr Arg His Ile Asp Cys Ala His Val
35 40 45
Tyr Gln Asn Glu Asn Glu Val Gly Val Ala Ile Gln Glu Lys Leu Arg
50 55 60
Glu Gln Val Val Lys Arg Glu Glu Leu Phe Ile Val Ser Lys Leu Trp
65 70 75 80
Cys Thr Tyr His Glu Lys Gly Leu Val Lys Gly Ala Cys Gln Lys Thr
85 90 95
Leu Ser Asp Leu Lys Leu Asp Tyr Leu Asp Leu Tyr Leu Ile His Trp
100 105 110
Pro Thr Gly Phe Lys Pro Gly Lys Glu Phe Phe Pro Leu Asp Glu Ser
115 120 125
Gly Asn Val Val Pro Ser Asp Thr Asn Ile Leu Asp Thr Trp Ala Ala
130 135 140
Met Glu Glu Leu Val Asp Glu Gly Leu Val Lys Ala Ile Gly Ile Ser
145 150 155 160
Asn Phe Asn His Leu Gln Val Glu Met Ile Leu Asn Lys Pro Gly Leu
165 170 175
Lys Tyr Lys Pro Ala Val Asn Gln Ile Glu Cys His Pro Tyr Leu Thr
180 185 190
Gln Glu Lys Leu Ile Gln Tyr Cys Gln Ser Lys Gly Ile Val Val Thr
195 200 205
Ala Tyr Ser Pro Leu Gly Ser Pro Asp Arg Pro Trp Ala Lys Pro Glu
210 215 220
Asp Pro Ser Leu Leu Glu Asp Pro Arg Ile Lys Ala Ile Ala Ala Lys
225 230 235 240
His Asn Lys Thr Thr Ala Gln Val Leu Ile Arg Phe Pro Met Gln Arg
245 250 255
Asn Leu Val Val Ile Pro Lys Ser Val Thr Pro Glu Arg Ile Ala Glu
260 265 270
Asn Phe Lys Val Phe Asp Phe Glu Leu Ser Ser Gln Asp Met Thr Thr
275 280 285
Leu Leu Ser Tyr Asn Arg Asn Trp Arg Val Cys Ala Leu Leu Ser Cys
290 295 300
Thr Ser His Lys Asp Tyr Pro Phe His Glu Glu Phe
305 310 315
<210> 6
<211> 480
<212> PRT
<213> 智人
<400> 6
Met Ser Asp Val Ala Ile Val Lys Glu Gly Trp Leu His Lys Arg Gly
1 5 10 15
Glu Tyr Ile Lys Thr Trp Arg Pro Arg Tyr Phe Leu Leu Lys Asn Asp
20 25 30
Gly Thr Phe Ile Gly Tyr Lys Glu Arg Pro Gln Asp Val Asp Gln Arg
35 40 45
Glu Ala Pro Leu Asn Asn Phe Ser Val Ala Gln Cys Gln Leu Met Lys
50 55 60
Thr Glu Arg Pro Arg Pro Asn Thr Phe Ile Ile Arg Cys Leu Gln Trp
65 70 75 80
Thr Thr Val Ile Glu Arg Thr Phe His Val Glu Thr Pro Glu Glu Arg
85 90 95
Glu Glu Trp Thr Thr Ala Ile Gln Thr Val Ala Asp Gly Leu Lys Lys
100 105 110
Gln Glu Glu Glu Glu Met Asp Phe Arg Ser Gly Ser Pro Ser Asp Asn
115 120 125
Ser Gly Ala Glu Glu Met Glu Val Ser Leu Ala Lys Pro Lys His Arg
130 135 140
Val Thr Met Asn Glu Phe Glu Tyr Leu Lys Leu Leu Gly Lys Gly Thr
145 150 155 160
Phe Gly Lys Val Ile Leu Val Lys Glu Lys Ala Thr Gly Arg Tyr Tyr
165 170 175
Ala Met Lys Ile Leu Lys Lys Glu Val Ile Val Ala Lys Asp Glu Val
180 185 190
Ala His Thr Leu Thr Glu Asn Arg Val Leu Gln Asn Ser Arg His Pro
195 200 205
Phe Leu Thr Ala Leu Lys Tyr Ser Phe Gln Thr His Asp Arg Leu Cys
210 215 220
Phe Val Met Glu Tyr Ala Asn Gly Gly Glu Leu Phe Phe His Leu Ser
225 230 235 240
Arg Glu Arg Val Phe Ser Glu Asp Arg Ala Arg Phe Tyr Gly Ala Glu
245 250 255
Ile Val Ser Ala Leu Asp Tyr Leu His Ser Glu Lys Asn Val Val Tyr
260 265 270
Arg Asp Leu Lys Leu Glu Asn Leu Met Leu Asp Lys Asp Gly His Ile
275 280 285
Lys Ile Thr Asp Phe Gly Leu Cys Lys Glu Gly Ile Lys Asp Gly Ala
290 295 300
Thr Met Lys Thr Phe Cys Gly Thr Pro Glu Tyr Leu Ala Pro Glu Val
305 310 315 320
Leu Glu Asp Asn Asp Tyr Gly Arg Ala Val Asp Trp Trp Gly Leu Gly
325 330 335
Val Val Met Tyr Glu Met Met Cys Gly Arg Leu Pro Phe Tyr Asn Gln
340 345 350
Asp His Glu Lys Leu Phe Glu Leu Ile Leu Met Glu Glu Ile Arg Phe
355 360 365
Pro Arg Thr Leu Gly Pro Glu Ala Lys Ser Leu Leu Ser Gly Leu Leu
370 375 380
Lys Lys Asp Pro Lys Gln Arg Leu Gly Gly Gly Ser Glu Asp Ala Lys
385 390 395 400
Glu Ile Met Gln His Arg Phe Phe Ala Gly Ile Val Trp Gln His Val
405 410 415
Tyr Glu Lys Lys Leu Ser Pro Pro Phe Lys Pro Gln Val Thr Ser Glu
420 425 430
Thr Asp Thr Arg Tyr Phe Asp Glu Glu Phe Thr Ala Gln Met Ile Thr
435 440 445
Ile Thr Pro Pro Asp Gln Asp Asp Ser Met Glu Cys Val Asp Ser Glu
450 455 460
Arg Arg Pro His Phe Pro Gln Phe Ser Tyr Ser Ala Ser Gly Thr Ala
465 470 475 480
<210> 7
<211> 609
<212> PRT
<213> 智人
<400> 7
Met Lys Trp Val Thr Phe Ile Ser Leu Leu Phe Leu Phe Ser Ser Ala
1 5 10 15
Tyr Ser Arg Gly Val Phe Arg Arg Asp Ala His Lys Ser Glu Val Ala
20 25 30
His Arg Phe Lys Asp Leu Gly Glu Glu Asn Phe Lys Ala Leu Val Leu
35 40 45
Ile Ala Phe Ala Gln Tyr Leu Gln Gln Cys Pro Phe Glu Asp His Val
50 55 60
Lys Leu Val Asn Glu Val Thr Glu Phe Ala Lys Thr Cys Val Ala Asp
65 70 75 80
Glu Ser Ala Glu Asn Cys Asp Lys Ser Leu His Thr Leu Phe Gly Asp
85 90 95
Lys Leu Cys Thr Val Ala Thr Leu Arg Glu Thr Tyr Gly Glu Met Ala
100 105 110
Asp Cys Cys Ala Lys Gln Glu Pro Glu Arg Asn Glu Cys Phe Leu Gln
115 120 125
His Lys Asp Asp Asn Pro Asn Leu Pro Arg Leu Val Arg Pro Glu Val
130 135 140
Asp Val Met Cys Thr Ala Phe His Asp Asn Glu Glu Thr Phe Leu Lys
145 150 155 160
Lys Tyr Leu Tyr Glu Ile Ala Arg Arg His Pro Tyr Phe Tyr Ala Pro
165 170 175
Glu Leu Leu Phe Phe Ala Lys Arg Tyr Lys Ala Ala Phe Thr Glu Cys
180 185 190
Cys Gln Ala Ala Asp Lys Ala Ala Cys Leu Leu Pro Lys Leu Asp Glu
195 200 205
Leu Arg Asp Glu Gly Lys Ala Ser Ser Ala Lys Gln Arg Leu Lys Cys
210 215 220
Ala Ser Leu Gln Lys Phe Gly Glu Arg Ala Phe Lys Ala Trp Ala Val
225 230 235 240
Ala Arg Leu Ser Gln Arg Phe Pro Lys Ala Glu Phe Ala Glu Val Ser
245 250 255
Lys Leu Val Thr Asp Leu Thr Lys Val His Thr Glu Cys Cys His Gly
260 265 270
Asp Leu Leu Glu Cys Ala Asp Asp Arg Ala Asp Leu Ala Lys Tyr Ile
275 280 285
Cys Glu Asn Gln Asp Ser Ile Ser Ser Lys Leu Lys Glu Cys Cys Glu
290 295 300
Lys Pro Leu Leu Glu Lys Ser His Cys Ile Ala Glu Val Glu Asn Asp
305 310 315 320
Glu Met Pro Ala Asp Leu Pro Ser Leu Ala Ala Asp Phe Val Glu Ser
325 330 335
Lys Asp Val Cys Lys Asn Tyr Ala Glu Ala Lys Asp Val Phe Leu Gly
340 345 350
Met Phe Leu Tyr Glu Tyr Ala Arg Arg His Pro Asp Tyr Ser Val Val
355 360 365
Leu Leu Leu Arg Leu Ala Lys Thr Tyr Glu Thr Thr Leu Glu Lys Cys
370 375 380
Cys Ala Ala Ala Asp Pro His Glu Cys Tyr Ala Lys Val Phe Asp Glu
385 390 395 400
Phe Lys Pro Leu Val Glu Glu Pro Gln Asn Leu Ile Lys Gln Asn Cys
405 410 415
Glu Leu Phe Glu Gln Leu Gly Glu Tyr Lys Phe Gln Asn Ala Leu Leu
420 425 430
Val Arg Tyr Thr Lys Lys Val Pro Gln Val Ser Thr Pro Thr Leu Val
435 440 445
Glu Val Ser Arg Asn Leu Gly Lys Val Gly Ser Lys Cys Cys Lys His
450 455 460
Pro Glu Ala Lys Arg Met Pro Cys Ala Glu Asp Tyr Leu Ser Val Val
465 470 475 480
Leu Asn Gln Leu Cys Val Leu His Glu Lys Thr Pro Val Ser Asp Arg
485 490 495
Val Thr Lys Cys Cys Thr Glu Ser Leu Val Asn Arg Arg Pro Cys Phe
500 505 510
Ser Ala Leu Glu Val Asp Glu Thr Tyr Val Pro Lys Glu Phe Asn Ala
515 520 525
Glu Thr Phe Thr Phe His Ala Asp Ile Cys Thr Leu Ser Glu Lys Glu
530 535 540
Arg Gln Ile Lys Lys Gln Thr Ala Leu Val Glu Leu Val Lys His Lys
545 550 555 560
Pro Lys Ala Thr Lys Glu Gln Leu Lys Ala Val Met Asp Asp Phe Ala
565 570 575
Ala Phe Val Glu Lys Cys Cys Lys Ala Asp Asp Lys Glu Thr Cys Phe
580 585 590
Ala Glu Glu Gly Lys Lys Leu Val Ala Ala Ser Gln Ala Ala Leu Gly
595 600 605
Leu
<210> 8
<211> 501
<212> PRT
<213> 智人
<400> 8
Met Ser Ser Ser Gly Thr Pro Asp Leu Pro Val Leu Leu Thr Asp Leu
1 5 10 15
Lys Ile Gln Tyr Thr Lys Ile Phe Ile Asn Asn Glu Trp His Asp Ser
20 25 30
Val Ser Gly Lys Lys Phe Pro Val Phe Asn Pro Ala Thr Glu Glu Glu
35 40 45
Leu Cys Gln Val Glu Glu Gly Asp Lys Glu Asp Val Asp Lys Ala Val
50 55 60
Lys Ala Ala Arg Gln Ala Phe Gln Ile Gly Ser Pro Trp Arg Thr Met
65 70 75 80
Asp Ala Ser Glu Arg Gly Arg Leu Leu Tyr Lys Leu Ala Asp Leu Ile
85 90 95
Glu Arg Asp Arg Leu Leu Leu Ala Thr Met Glu Ser Met Asn Gly Gly
100 105 110
Lys Leu Tyr Ser Asn Ala Tyr Leu Asn Asp Leu Ala Gly Cys Ile Lys
115 120 125
Thr Leu Arg Tyr Cys Ala Gly Trp Ala Asp Lys Ile Gln Gly Arg Thr
130 135 140
Ile Pro Ile Asp Gly Asn Phe Phe Thr Tyr Thr Arg His Glu Pro Ile
145 150 155 160
Gly Val Cys Gly Gln Ile Ile Pro Trp Asn Phe Pro Leu Val Met Leu
165 170 175
Ile Trp Lys Ile Gly Pro Ala Leu Ser Cys Gly Asn Thr Val Val Val
180 185 190
Lys Pro Ala Glu Gln Thr Pro Leu Thr Ala Leu His Val Ala Ser Leu
195 200 205
Ile Lys Glu Ala Gly Phe Pro Pro Gly Val Val Asn Ile Val Pro Gly
210 215 220
Tyr Gly Pro Thr Ala Gly Ala Ala Ile Ser Ser His Met Asp Ile Asp
225 230 235 240
Lys Val Ala Phe Thr Gly Ser Thr Glu Val Gly Lys Leu Ile Lys Glu
245 250 255
Ala Ala Gly Lys Ser Asn Leu Lys Arg Val Thr Leu Glu Leu Gly Gly
260 265 270
Lys Ser Pro Cys Ile Val Leu Ala Asp Ala Asp Leu Asp Asn Ala Val
275 280 285
Glu Phe Ala His His Gly Val Phe Tyr His Gln Gly Gln Cys Cys Ile
290 295 300
Ala Ala Ser Arg Ile Phe Val Glu Glu Ser Ile Tyr Asp Glu Phe Val
305 310 315 320
Arg Arg Ser Val Glu Arg Ala Lys Lys Tyr Ile Leu Gly Asn Pro Leu
325 330 335
Thr Pro Gly Val Thr Gln Gly Pro Gln Ile Asp Lys Glu Gln Tyr Asp
340 345 350
Lys Ile Leu Asp Leu Ile Glu Ser Gly Lys Lys Glu Gly Ala Lys Leu
355 360 365
Glu Cys Gly Gly Gly Pro Trp Gly Asn Lys Gly Tyr Phe Val Gln Pro
370 375 380
Thr Val Phe Ser Asn Val Thr Asp Glu Met Arg Ile Ala Lys Glu Glu
385 390 395 400
Ile Phe Gly Pro Val Gln Gln Ile Met Lys Phe Lys Ser Leu Asp Asp
405 410 415
Val Ile Lys Arg Ala Asn Asn Thr Phe Tyr Gly Leu Ser Ala Gly Val
420 425 430
Phe Thr Lys Asp Ile Asp Lys Ala Ile Thr Ile Ser Ser Ala Leu Gln
435 440 445
Ala Gly Thr Val Trp Val Asn Cys Tyr Gly Val Val Ser Ala Gln Cys
450 455 460
Pro Phe Gly Gly Phe Lys Met Ser Gly Asn Gly Arg Glu Leu Gly Glu
465 470 475 480
Tyr Gly Phe His Glu Tyr Thr Glu Val Lys Thr Val Thr Val Lys Ile
485 490 495
Ser Gln Lys Asn Ser
500
<210> 9
<211> 517
<212> PRT
<213> 智人
<400> 9
Met Leu Arg Phe Leu Ala Pro Arg Leu Leu Ser Leu Gln Gly Arg Thr
1 5 10 15
Ala Arg Tyr Ser Ser Ala Ala Ala Leu Pro Ser Pro Ile Leu Asn Pro
20 25 30
Asp Ile Pro Tyr Asn Gln Leu Phe Ile Asn Asn Glu Trp Gln Asp Ala
35 40 45
Val Ser Lys Lys Thr Phe Pro Thr Val Asn Pro Thr Thr Gly Glu Val
50 55 60
Ile Gly His Val Ala Glu Gly Asp Arg Ala Asp Val Asp Arg Ala Val
65 70 75 80
Lys Ala Ala Arg Glu Ala Phe Arg Leu Gly Ser Pro Trp Arg Arg Met
85 90 95
Asp Ala Ser Glu Arg Gly Arg Leu Leu Asn Leu Leu Ala Asp Leu Val
100 105 110
Glu Arg Asp Arg Val Tyr Leu Ala Ser Leu Glu Thr Leu Asp Asn Gly
115 120 125
Lys Pro Phe Gln Glu Ser Tyr Ala Leu Asp Leu Asp Glu Val Ile Lys
130 135 140
Val Tyr Arg Tyr Phe Ala Gly Trp Ala Asp Lys Trp His Gly Lys Thr
145 150 155 160
Ile Pro Met Asp Gly Gln His Phe Cys Phe Thr Arg His Glu Pro Val
165 170 175
Gly Val Cys Gly Gln Ile Ile Pro Trp Asn Phe Pro Leu Val Met Gln
180 185 190
Gly Trp Lys Leu Ala Pro Ala Leu Ala Thr Gly Asn Thr Val Val Met
195 200 205
Lys Val Ala Glu Gln Thr Pro Leu Ser Ala Leu Tyr Leu Ala Ser Leu
210 215 220
Ile Lys Glu Ala Gly Phe Pro Pro Gly Val Val Asn Ile Ile Thr Gly
225 230 235 240
Tyr Gly Pro Thr Ala Gly Ala Ala Ile Ala Gln His Val Asp Val Asp
245 250 255
Lys Val Ala Phe Thr Gly Ser Thr Glu Val Gly His Leu Ile Gln Lys
260 265 270
Ala Ala Gly Asp Ser Asn Leu Lys Arg Val Thr Leu Glu Leu Gly Gly
275 280 285
Lys Ser Pro Ser Ile Val Leu Ala Asp Ala Asp Met Glu His Ala Val
290 295 300
Glu Gln Cys His Glu Ala Leu Phe Phe Asn Met Gly Gln Cys Cys Cys
305 310 315 320
Ala Gly Ser Arg Thr Phe Val Glu Glu Ser Ile Tyr Asn Glu Phe Leu
325 330 335
Glu Arg Thr Val Glu Lys Ala Lys Gln Arg Lys Val Gly Asn Pro Phe
340 345 350
Glu Leu Asp Thr Gln Gln Gly Pro Gln Val Asp Lys Glu Gln Phe Glu
355 360 365
Arg Val Leu Gly Tyr Ile Gln Leu Gly Gln Lys Glu Gly Ala Lys Leu
370 375 380
Leu Cys Gly Gly Glu Arg Phe Gly Glu Arg Gly Phe Phe Ile Lys Pro
385 390 395 400
Thr Val Phe Gly Gly Val Gln Asp Asp Met Arg Ile Ala Lys Glu Glu
405 410 415
Ile Phe Gly Pro Val Gln Pro Leu Phe Lys Phe Lys Lys Ile Glu Glu
420 425 430
Val Val Glu Arg Ala Asn Asn Thr Arg Tyr Gly Leu Ala Ala Ala Val
435 440 445
Phe Thr Arg Asp Leu Asp Lys Ala Met Tyr Phe Thr Gln Ala Leu Gln
450 455 460
Ala Gly Thr Val Trp Val Asn Thr Tyr Asn Ile Val Thr Cys His Thr
465 470 475 480
Pro Phe Gly Gly Phe Lys Glu Ser Gly Asn Gly Arg Glu Leu Gly Glu
485 490 495
Asp Gly Leu Lys Ala Tyr Thr Glu Val Lys Thr Val Thr Ile Lys Val
500 505 510
Pro Gln Lys Asn Ser
515
<210> 10
<211> 364
<212> PRT
<213> 智人
<400> 10
Met Pro Tyr Gln Tyr Pro Ala Leu Thr Pro Glu Gln Lys Lys Glu Leu
1 5 10 15
Ser Asp Ile Ala His Arg Ile Val Ala Pro Gly Lys Gly Ile Leu Ala
20 25 30
Ala Asp Glu Ser Thr Gly Ser Ile Ala Lys Arg Leu Gln Ser Ile Gly
35 40 45
Thr Glu Asn Thr Glu Glu Asn Arg Arg Phe Tyr Arg Gln Leu Leu Leu
50 55 60
Thr Ala Asp Asp Arg Val Asn Pro Cys Ile Gly Gly Val Ile Leu Phe
65 70 75 80
His Glu Thr Leu Tyr Gln Lys Ala Asp Asp Gly Arg Pro Phe Pro Gln
85 90 95
Val Ile Lys Ser Lys Gly Gly Val Val Gly Ile Lys Val Asp Lys Gly
100 105 110
Val Val Pro Leu Ala Gly Thr Asn Gly Glu Thr Thr Thr Gln Gly Leu
115 120 125
Asp Gly Leu Ser Glu Arg Cys Ala Gln Tyr Lys Lys Asp Gly Ala Asp
130 135 140
Phe Ala Lys Trp Arg Cys Val Leu Lys Ile Gly Glu His Thr Pro Ser
145 150 155 160
Ala Leu Ala Ile Met Glu Asn Ala Asn Val Leu Ala Arg Tyr Ala Ser
165 170 175
Ile Cys Gln Gln Asn Gly Ile Val Pro Ile Val Glu Pro Glu Ile Leu
180 185 190
Pro Asp Gly Asp His Asp Leu Lys Arg Cys Gln Tyr Val Thr Glu Lys
195 200 205
Val Leu Ala Ala Val Tyr Lys Ala Leu Ser Asp His His Ile Tyr Leu
210 215 220
Glu Gly Thr Leu Leu Lys Pro Asn Met Val Thr Pro Gly His Ala Cys
225 230 235 240
Thr Gln Lys Phe Ser His Glu Glu Ile Ala Met Ala Thr Val Thr Ala
245 250 255
Leu Arg Arg Thr Val Pro Pro Ala Val Thr Gly Ile Thr Phe Leu Ser
260 265 270
Gly Gly Gln Ser Glu Glu Glu Ala Ser Ile Asn Leu Asn Ala Ile Asn
275 280 285
Lys Cys Pro Leu Leu Lys Pro Trp Ala Leu Thr Phe Ser Tyr Gly Arg
290 295 300
Ala Leu Gln Ala Ser Ala Leu Lys Ala Trp Gly Gly Lys Lys Glu Asn
305 310 315 320
Leu Lys Ala Ala Gln Glu Glu Tyr Val Lys Arg Ala Leu Ala Asn Ser
325 330 335
Leu Ala Cys Gln Gly Lys Tyr Thr Pro Ser Gly Gln Ala Gly Ala Ala
340 345 350
Ala Ser Glu Ser Leu Phe Val Ser Asn His Ala Tyr
355 360
<210> 11
<211> 511
<212> PRT
<213> 智人
<400> 11
Met Lys Phe Phe Leu Leu Leu Phe Thr Ile Gly Phe Cys Trp Ala Gln
1 5 10 15
Tyr Ser Pro Asn Thr Gln Gln Gly Arg Thr Ser Ile Val His Leu Phe
20 25 30
Glu Trp Arg Trp Val Asp Ile Ala Leu Glu Cys Glu Arg Tyr Leu Ala
35 40 45
Pro Lys Gly Phe Gly Gly Val Gln Val Ser Pro Pro Asn Glu Asn Val
50 55 60
Ala Ile His Asn Pro Phe Arg Pro Trp Trp Glu Arg Tyr Gln Pro Val
65 70 75 80
Ser Tyr Lys Leu Cys Thr Arg Ser Gly Asn Glu Asp Glu Phe Arg Asn
85 90 95
Met Val Thr Arg Cys Asn Asn Val Gly Val Arg Ile Tyr Val Asp Ala
100 105 110
Val Ile Asn His Met Ser Gly Asn Ala Val Ser Ala Gly Thr Ser Ser
115 120 125
Thr Cys Gly Ser Tyr Phe Asn Pro Gly Ser Arg Asp Phe Pro Ala Val
130 135 140
Pro Tyr Ser Gly Trp Asp Phe Asn Asp Gly Lys Cys Lys Thr Gly Ser
145 150 155 160
Gly Asp Ile Glu Asn Tyr Asn Asp Ala Thr Gln Val Arg Asp Cys Arg
165 170 175
Leu Val Gly Leu Leu Asp Leu Ala Leu Glu Lys Asp Tyr Val Arg Ser
180 185 190
Lys Ile Ala Glu Tyr Met Asn His Leu Ile Asp Ile Gly Val Ala Gly
195 200 205
Phe Arg Leu Asp Ala Ser Lys His Met Trp Pro Gly Asp Ile Lys Ala
210 215 220
Ile Leu Asp Lys Leu His Asn Leu Asn Ser Asn Trp Phe Pro Ala Gly
225 230 235 240
Ser Lys Pro Phe Ile Tyr Gln Glu Val Ile Asp Leu Gly Gly Glu Pro
245 250 255
Ile Lys Ser Ser Asp Tyr Phe Gly Asn Gly Arg Val Thr Glu Phe Lys
260 265 270
Tyr Gly Ala Lys Leu Gly Thr Val Ile Arg Lys Trp Asn Gly Glu Lys
275 280 285
Met Ser Tyr Leu Lys Asn Trp Gly Glu Gly Trp Gly Phe Met Pro Ser
290 295 300
Asp Arg Ala Leu Val Phe Val Asp Asn His Asp Asn Gln Arg Gly His
305 310 315 320
Gly Ala Gly Gly Ala Ser Ile Leu Thr Phe Trp Asp Ala Arg Leu Tyr
325 330 335
Lys Met Ala Val Gly Phe Met Leu Ala His Pro Tyr Gly Phe Thr Arg
340 345 350
Val Met Ser Ser Tyr Arg Trp Pro Arg Gln Phe Gln Asn Gly Asn Asp
355 360 365
Val Asn Asp Trp Val Gly Pro Pro Asn Asn Asn Gly Val Ile Lys Glu
370 375 380
Val Thr Ile Asn Pro Asp Thr Thr Cys Gly Asn Asp Trp Val Cys Glu
385 390 395 400
His Arg Trp Arg Gln Ile Arg Asn Met Val Asn Phe Arg Asn Val Val
405 410 415
Asp Gly Gln Pro Phe Thr Asn Trp Tyr Asp Asn Gly Ser Asn Gln Val
420 425 430
Ala Phe Gly Arg Gly Asn Arg Gly Phe Ile Val Phe Asn Asn Asp Asp
435 440 445
Trp Thr Phe Ser Leu Thr Leu Gln Thr Gly Leu Pro Ala Gly Thr Tyr
450 455 460
Cys Asp Val Ile Ser Gly Asp Lys Ile Asn Gly Asn Cys Thr Gly Ile
465 470 475 480
Lys Ile Tyr Val Ser Asp Asp Gly Lys Ala His Phe Ser Ile Ser Asn
485 490 495
Ser Ala Glu Asp Pro Phe Ile Ala Ile His Ala Glu Ser Lys Leu
500 505 510
<210> 12
<211> 346
<212> PRT
<213> 智人
<400> 12
Met Ala Met Val Ser Glu Phe Leu Lys Gln Ala Trp Phe Ile Glu Asn
1 5 10 15
Glu Glu Gln Glu Tyr Val Gln Thr Val Lys Ser Ser Lys Gly Gly Pro
20 25 30
Gly Ser Ala Val Ser Pro Tyr Pro Thr Phe Asn Pro Ser Ser Asp Val
35 40 45
Ala Ala Leu His Lys Ala Ile Met Val Lys Gly Val Asp Glu Ala Thr
50 55 60
Ile Ile Asp Ile Leu Thr Lys Arg Asn Asn Ala Gln Arg Gln Gln Ile
65 70 75 80
Lys Ala Ala Tyr Leu Gln Glu Thr Gly Lys Pro Leu Asp Glu Thr Leu
85 90 95
Lys Lys Ala Leu Thr Gly His Leu Glu Glu Val Val Leu Ala Leu Leu
100 105 110
Lys Thr Pro Ala Gln Phe Asp Ala Asp Glu Leu Arg Ala Ala Met Lys
115 120 125
Gly Leu Gly Thr Asp Glu Asp Thr Leu Ile Glu Ile Leu Ala Ser Arg
130 135 140
Thr Asn Lys Glu Ile Arg Asp Ile Asn Arg Val Tyr Arg Glu Glu Leu
145 150 155 160
Lys Arg Asp Leu Ala Lys Asp Ile Thr Ser Asp Thr Ser Gly Asp Phe
165 170 175
Arg Asn Ala Leu Leu Ser Leu Ala Lys Gly Asp Arg Ser Glu Asp Phe
180 185 190
Gly Val Asn Glu Asp Leu Ala Asp Ser Asp Ala Arg Ala Leu Tyr Glu
195 200 205
Ala Gly Glu Arg Arg Lys Gly Thr Asp Val Asn Val Phe Asn Thr Ile
210 215 220
Leu Thr Thr Arg Ser Tyr Pro Gln Leu Arg Arg Val Phe Gln Lys Tyr
225 230 235 240
Thr Lys Tyr Ser Lys His Asp Met Asn Lys Val Leu Asp Leu Glu Leu
245 250 255
Lys Gly Asp Ile Glu Lys Cys Leu Thr Ala Ile Val Lys Cys Ala Thr
260 265 270
Ser Lys Pro Ala Phe Phe Ala Glu Lys Leu His Gln Ala Met Lys Gly
275 280 285
Val Gly Thr Arg His Lys Ala Leu Ile Arg Ile Met Val Ser Arg Ser
290 295 300
Glu Ile Asp Met Asn Asp Ile Lys Ala Phe Tyr Gln Lys Met Tyr Gly
305 310 315 320
Ile Ser Leu Cys Gln Ala Ile Leu Asp Glu Thr Lys Gly Asp Tyr Glu
325 330 335
Lys Ile Leu Val Ala Leu Cys Gly Gly Asn
340 345
<210> 13
<211> 323
<212> PRT
<213> 智人
<400> 13
Met Ala Ser Ile Trp Val Gly His Arg Gly Thr Val Arg Asp Tyr Pro
1 5 10 15
Asp Phe Ser Pro Ser Val Asp Ala Glu Ala Ile Gln Lys Ala Ile Arg
20 25 30
Gly Ile Gly Thr Asp Glu Lys Met Leu Ile Ser Ile Leu Thr Glu Arg
35 40 45
Ser Asn Ala Gln Arg Gln Leu Ile Val Lys Glu Tyr Gln Ala Ala Tyr
50 55 60
Gly Lys Glu Leu Lys Asp Asp Leu Lys Gly Asp Leu Ser Gly His Phe
65 70 75 80
Glu His Leu Met Val Ala Leu Val Thr Pro Pro Ala Val Phe Asp Ala
85 90 95
Lys Gln Leu Lys Lys Ser Met Lys Gly Ala Gly Thr Asn Glu Asp Ala
100 105 110
Leu Ile Glu Ile Leu Thr Thr Arg Thr Ser Arg Gln Met Lys Asp Ile
115 120 125
Ser Gln Ala Tyr Tyr Thr Val Tyr Lys Lys Ser Leu Gly Asp Asp Ile
130 135 140
Ser Ser Glu Thr Ser Gly Asp Phe Arg Lys Ala Leu Leu Thr Leu Ala
145 150 155 160
Asp Gly Arg Arg Asp Glu Ser Leu Lys Val Asp Glu His Leu Ala Lys
165 170 175
Gln Asp Ala Gln Ile Leu Tyr Lys Ala Gly Glu Asn Arg Trp Gly Thr
180 185 190
Asp Glu Asp Lys Phe Thr Glu Ile Leu Cys Leu Arg Ser Phe Pro Gln
195 200 205
Leu Lys Leu Thr Phe Asp Glu Tyr Arg Asn Ile Ser Gln Lys Asp Ile
210 215 220
Val Asp Ser Ile Lys Gly Glu Leu Ser Gly His Phe Glu Asp Leu Leu
225 230 235 240
Leu Ala Ile Val Asn Cys Val Arg Asn Thr Pro Ala Phe Leu Ala Glu
245 250 255
Arg Leu His Arg Ala Leu Lys Gly Ile Gly Thr Asp Glu Phe Thr Leu
260 265 270
Asn Arg Ile Met Val Ser Arg Ser Glu Ile Asp Leu Leu Asp Ile Arg
275 280 285
Thr Glu Phe Lys Lys His Tyr Gly Tyr Ser Leu Tyr Ser Ala Ile Lys
290 295 300
Ser Asp Thr Ser Gly Asp Tyr Glu Ile Thr Leu Leu Lys Ile Cys Gly
305 310 315 320
Gly Asp Asp
<210> 14
<211> 319
<212> PRT
<213> 智人
<400> 14
Met Ala Thr Lys Gly Gly Thr Val Lys Ala Ala Ser Gly Phe Asn Ala
1 5 10 15
Met Glu Asp Ala Gln Thr Leu Arg Lys Ala Met Lys Gly Leu Gly Thr
20 25 30
Asp Glu Asp Ala Ile Ile Ser Val Leu Ala Tyr Arg Asn Thr Ala Gln
35 40 45
Arg Gln Glu Ile Arg Thr Ala Tyr Lys Ser Thr Ile Gly Arg Asp Leu
50 55 60
Ile Asp Asp Leu Lys Ser Glu Leu Ser Gly Asn Phe Glu Gln Val Ile
65 70 75 80
Val Gly Met Met Thr Pro Thr Val Leu Tyr Asp Val Gln Glu Leu Arg
85 90 95
Arg Ala Met Lys Gly Ala Gly Thr Asp Glu Gly Cys Leu Ile Glu Ile
100 105 110
Leu Ala Ser Arg Thr Pro Glu Glu Ile Arg Arg Ile Ser Gln Thr Tyr
115 120 125
Gln Gln Gln Tyr Gly Arg Ser Leu Glu Asp Asp Ile Arg Ser Asp Thr
130 135 140
Ser Phe Met Phe Gln Arg Val Leu Val Ser Leu Ser Ala Gly Gly Arg
145 150 155 160
Asp Glu Gly Asn Tyr Leu Asp Asp Ala Leu Val Arg Gln Asp Ala Gln
165 170 175
Asp Leu Tyr Glu Ala Gly Glu Lys Lys Trp Gly Thr Asp Glu Val Lys
180 185 190
Phe Leu Thr Val Leu Cys Ser Arg Asn Arg Asn His Leu Leu His Val
195 200 205
Phe Asp Glu Tyr Lys Arg Ile Ser Gln Lys Asp Ile Glu Gln Ser Ile
210 215 220
Lys Ser Glu Thr Ser Gly Ser Phe Glu Asp Ala Leu Leu Ala Ile Val
225 230 235 240
Lys Cys Met Arg Asn Lys Ser Ala Tyr Phe Ala Glu Lys Leu Tyr Lys
245 250 255
Ser Met Lys Gly Leu Gly Thr Asp Asp Asn Thr Leu Ile Arg Val Met
260 265 270
Val Ser Arg Ala Glu Ile Asp Met Leu Asp Ile Arg Ala His Phe Lys
275 280 285
Arg Leu Tyr Gly Lys Ser Leu Tyr Ser Phe Ile Lys Gly Asp Thr Ser
290 295 300
Gly Asp Tyr Arg Lys Val Leu Leu Val Leu Cys Gly Gly Asp Asp
305 310 315
<210> 15
<211> 320
<212> PRT
<213> 智人
<400> 15
Met Ala Gln Val Leu Arg Gly Thr Val Thr Asp Phe Pro Gly Phe Asp
1 5 10 15
Glu Arg Ala Asp Ala Glu Thr Leu Arg Lys Ala Met Lys Gly Leu Gly
20 25 30
Thr Asp Glu Glu Ser Ile Leu Thr Leu Leu Thr Ser Arg Ser Asn Ala
35 40 45
Gln Arg Gln Glu Ile Ser Ala Ala Phe Lys Thr Leu Phe Gly Arg Asp
50 55 60
Leu Leu Asp Asp Leu Lys Ser Glu Leu Thr Gly Lys Phe Glu Lys Leu
65 70 75 80
Ile Val Ala Leu Met Lys Pro Ser Arg Leu Tyr Asp Ala Tyr Glu Leu
85 90 95
Lys His Ala Leu Lys Gly Ala Gly Thr Asn Glu Lys Val Leu Thr Glu
100 105 110
Ile Ile Ala Ser Arg Thr Pro Glu Glu Leu Arg Ala Ile Lys Gln Val
115 120 125
Tyr Glu Glu Glu Tyr Gly Ser Ser Leu Glu Asp Asp Val Val Gly Asp
130 135 140
Thr Ser Gly Tyr Tyr Gln Arg Met Leu Val Val Leu Leu Gln Ala Asn
145 150 155 160
Arg Asp Pro Asp Ala Gly Ile Asp Glu Ala Gln Val Glu Gln Asp Ala
165 170 175
Gln Ala Leu Phe Gln Ala Gly Glu Leu Lys Trp Gly Thr Asp Glu Glu
180 185 190
Lys Phe Ile Thr Ile Phe Gly Thr Arg Ser Val Ser His Leu Arg Lys
195 200 205
Val Phe Asp Lys Tyr Met Thr Ile Ser Gly Phe Gln Ile Glu Glu Thr
210 215 220
Ile Asp Arg Glu Thr Ser Gly Asn Leu Glu Gln Leu Leu Leu Ala Val
225 230 235 240
Val Lys Ser Ile Arg Ser Ile Pro Ala Tyr Leu Ala Glu Thr Leu Tyr
245 250 255
Tyr Ala Met Lys Gly Ala Gly Thr Asp Asp His Thr Leu Ile Arg Val
260 265 270
Met Val Ser Arg Ser Glu Ile Asp Leu Phe Asn Ile Arg Lys Glu Phe
275 280 285
Arg Lys Asn Phe Ala Thr Ser Leu Tyr Ser Met Ile Lys Gly Asp Thr
290 295 300
Ser Gly Asp Tyr Lys Lys Ala Leu Leu Leu Leu Cys Gly Glu Asp Asp
305 310 315 320
<210> 16
<211> 2843
<212> PRT
<213> 智人
<400> 16
Met Ala Ala Ala Ser Tyr Asp Gln Leu Leu Lys Gln Val Glu Ala Leu
1 5 10 15
Lys Met Glu Asn Ser Asn Leu Arg Gln Glu Leu Glu Asp Asn Ser Asn
20 25 30
His Leu Thr Lys Leu Glu Thr Glu Ala Ser Asn Met Lys Glu Val Leu
35 40 45
Lys Gln Leu Gln Gly Ser Ile Glu Asp Glu Ala Met Ala Ser Ser Gly
50 55 60
Gln Ile Asp Leu Leu Glu Arg Leu Lys Glu Leu Asn Leu Asp Ser Ser
65 70 75 80
Asn Phe Pro Gly Val Lys Leu Arg Ser Lys Met Ser Leu Arg Ser Tyr
85 90 95
Gly Ser Arg Glu Gly Ser Val Ser Ser Arg Ser Gly Glu Cys Ser Pro
100 105 110
Val Pro Met Gly Ser Phe Pro Arg Arg Gly Phe Val Asn Gly Ser Arg
115 120 125
Glu Ser Thr Gly Tyr Leu Glu Glu Leu Glu Lys Glu Arg Ser Leu Leu
130 135 140
Leu Ala Asp Leu Asp Lys Glu Glu Lys Glu Lys Asp Trp Tyr Tyr Ala
145 150 155 160
Gln Leu Gln Asn Leu Thr Lys Arg Ile Asp Ser Leu Pro Leu Thr Glu
165 170 175
Asn Phe Ser Leu Gln Thr Asp Met Thr Arg Arg Gln Leu Glu Tyr Glu
180 185 190
Ala Arg Gln Ile Arg Val Ala Met Glu Glu Gln Leu Gly Thr Cys Gln
195 200 205
Asp Met Glu Lys Arg Ala Gln Arg Arg Ile Ala Arg Ile Gln Gln Ile
210 215 220
Glu Lys Asp Ile Leu Arg Ile Arg Gln Leu Leu Gln Ser Gln Ala Thr
225 230 235 240
Glu Ala Glu Arg Ser Ser Gln Asn Lys His Glu Thr Gly Ser His Asp
245 250 255
Ala Glu Arg Gln Asn Glu Gly Gln Gly Val Gly Glu Ile Asn Met Ala
260 265 270
Thr Ser Gly Asn Gly Gln Gly Ser Thr Thr Arg Met Asp His Glu Thr
275 280 285
Ala Ser Val Leu Ser Ser Ser Ser Thr His Ser Ala Pro Arg Arg Leu
290 295 300
Thr Ser His Leu Gly Thr Lys Val Glu Met Val Tyr Ser Leu Leu Ser
305 310 315 320
Met Leu Gly Thr His Asp Lys Asp Asp Met Ser Arg Thr Leu Leu Ala
325 330 335
Met Ser Ser Ser Gln Asp Ser Cys Ile Ser Met Arg Gln Ser Gly Cys
340 345 350
Leu Pro Leu Leu Ile Gln Leu Leu His Gly Asn Asp Lys Asp Ser Val
355 360 365
Leu Leu Gly Asn Ser Arg Gly Ser Lys Glu Ala Arg Ala Arg Ala Ser
370 375 380
Ala Ala Leu His Asn Ile Ile His Ser Gln Pro Asp Asp Lys Arg Gly
385 390 395 400
Arg Arg Glu Ile Arg Val Leu His Leu Leu Glu Gln Ile Arg Ala Tyr
405 410 415
Cys Glu Thr Cys Trp Glu Trp Gln Glu Ala His Glu Pro Gly Met Asp
420 425 430
Gln Asp Lys Asn Pro Met Pro Ala Pro Val Glu His Gln Ile Cys Pro
435 440 445
Ala Val Cys Val Leu Met Lys Leu Ser Phe Asp Glu Glu His Arg His
450 455 460
Ala Met Asn Glu Leu Gly Gly Leu Gln Ala Ile Ala Glu Leu Leu Gln
465 470 475 480
Val Asp Cys Glu Met Tyr Gly Leu Thr Asn Asp His Tyr Ser Ile Thr
485 490 495
Leu Arg Arg Tyr Ala Gly Met Ala Leu Thr Asn Leu Thr Phe Gly Asp
500 505 510
Val Ala Asn Lys Ala Thr Leu Cys Ser Met Lys Gly Cys Met Arg Ala
515 520 525
Leu Val Ala Gln Leu Lys Ser Glu Ser Glu Asp Leu Gln Gln Val Ile
530 535 540
Ala Ser Val Leu Arg Asn Leu Ser Trp Arg Ala Asp Val Asn Ser Lys
545 550 555 560
Lys Thr Leu Arg Glu Val Gly Ser Val Lys Ala Leu Met Glu Cys Ala
565 570 575
Leu Glu Val Lys Lys Glu Ser Thr Leu Lys Ser Val Leu Ser Ala Leu
580 585 590
Trp Asn Leu Ser Ala His Cys Thr Glu Asn Lys Ala Asp Ile Cys Ala
595 600 605
Val Asp Gly Ala Leu Ala Phe Leu Val Gly Thr Leu Thr Tyr Arg Ser
610 615 620
Gln Thr Asn Thr Leu Ala Ile Ile Glu Ser Gly Gly Gly Ile Leu Arg
625 630 635 640
Asn Val Ser Ser Leu Ile Ala Thr Asn Glu Asp His Arg Gln Ile Leu
645 650 655
Arg Glu Asn Asn Cys Leu Gln Thr Leu Leu Gln His Leu Lys Ser His
660 665 670
Ser Leu Thr Ile Val Ser Asn Ala Cys Gly Thr Leu Trp Asn Leu Ser
675 680 685
Ala Arg Asn Pro Lys Asp Gln Glu Ala Leu Trp Asp Met Gly Ala Val
690 695 700
Ser Met Leu Lys Asn Leu Ile His Ser Lys His Lys Met Ile Ala Met
705 710 715 720
Gly Ser Ala Ala Ala Leu Arg Asn Leu Met Ala Asn Arg Pro Ala Lys
725 730 735
Tyr Lys Asp Ala Asn Ile Met Ser Pro Gly Ser Ser Leu Pro Ser Leu
740 745 750
His Val Arg Lys Gln Lys Ala Leu Glu Ala Glu Leu Asp Ala Gln His
755 760 765
Leu Ser Glu Thr Phe Asp Asn Ile Asp Asn Leu Ser Pro Lys Ala Ser
770 775 780
His Arg Ser Lys Gln Arg His Lys Gln Ser Leu Tyr Gly Asp Tyr Val
785 790 795 800
Phe Asp Thr Asn Arg His Asp Asp Asn Arg Ser Asp Asn Phe Asn Thr
805 810 815
Gly Asn Met Thr Val Leu Ser Pro Tyr Leu Asn Thr Thr Val Leu Pro
820 825 830
Ser Ser Ser Ser Ser Arg Gly Ser Leu Asp Ser Ser Arg Ser Glu Lys
835 840 845
Asp Arg Ser Leu Glu Arg Glu Arg Gly Ile Gly Leu Gly Asn Tyr His
850 855 860
Pro Ala Thr Glu Asn Pro Gly Thr Ser Ser Lys Arg Gly Leu Gln Ile
865 870 875 880
Ser Thr Thr Ala Ala Gln Ile Ala Lys Val Met Glu Glu Val Ser Ala
885 890 895
Ile His Thr Ser Gln Glu Asp Arg Ser Ser Gly Ser Thr Thr Glu Leu
900 905 910
His Cys Val Thr Asp Glu Arg Asn Ala Leu Arg Arg Ser Ser Ala Ala
915 920 925
His Thr His Ser Asn Thr Tyr Asn Phe Thr Lys Ser Glu Asn Ser Asn
930 935 940
Arg Thr Cys Ser Met Pro Tyr Ala Lys Leu Glu Tyr Lys Arg Ser Ser
945 950 955 960
Asn Asp Ser Leu Asn Ser Val Ser Ser Ser Asp Gly Tyr Gly Lys Arg
965 970 975
Gly Gln Met Lys Pro Ser Ile Glu Ser Tyr Ser Glu Asp Asp Glu Ser
980 985 990
Lys Phe Cys Ser Tyr Gly Gln Tyr Pro Ala Asp Leu Ala His Lys Ile
995 1000 1005
His Ser Ala Asn His Met Asp Asp Asn Asp Gly Glu Leu Asp Thr
1010 1015 1020
Pro Ile Asn Tyr Ser Leu Lys Tyr Ser Asp Glu Gln Leu Asn Ser
1025 1030 1035
Gly Arg Gln Ser Pro Ser Gln Asn Glu Arg Trp Ala Arg Pro Lys
1040 1045 1050
His Ile Ile Glu Asp Glu Ile Lys Gln Ser Glu Gln Arg Gln Ser
1055 1060 1065
Arg Asn Gln Ser Thr Thr Tyr Pro Val Tyr Thr Glu Ser Thr Asp
1070 1075 1080
Asp Lys His Leu Lys Phe Gln Pro His Phe Gly Gln Gln Glu Cys
1085 1090 1095
Val Ser Pro Tyr Arg Ser Arg Gly Ala Asn Gly Ser Glu Thr Asn
1100 1105 1110
Arg Val Gly Ser Asn His Gly Ile Asn Gln Asn Val Ser Gln Ser
1115 1120 1125
Leu Cys Gln Glu Asp Asp Tyr Glu Asp Asp Lys Pro Thr Asn Tyr
1130 1135 1140
Ser Glu Arg Tyr Ser Glu Glu Glu Gln His Glu Glu Glu Glu Arg
1145 1150 1155
Pro Thr Asn Tyr Ser Ile Lys Tyr Asn Glu Glu Lys Arg His Val
1160 1165 1170
Asp Gln Pro Ile Asp Tyr Ser Leu Lys Tyr Ala Thr Asp Ile Pro
1175 1180 1185
Ser Ser Gln Lys Gln Ser Phe Ser Phe Ser Lys Ser Ser Ser Gly
1190 1195 1200
Gln Ser Ser Lys Thr Glu His Met Ser Ser Ser Ser Glu Asn Thr
1205 1210 1215
Ser Thr Pro Ser Ser Asn Ala Lys Arg Gln Asn Gln Leu His Pro
1220 1225 1230
Ser Ser Ala Gln Ser Arg Ser Gly Gln Pro Gln Lys Ala Ala Thr
1235 1240 1245
Cys Lys Val Ser Ser Ile Asn Gln Glu Thr Ile Gln Thr Tyr Cys
1250 1255 1260
Val Glu Asp Thr Pro Ile Cys Phe Ser Arg Cys Ser Ser Leu Ser
1265 1270 1275
Ser Leu Ser Ser Ala Glu Asp Glu Ile Gly Cys Asn Gln Thr Thr
1280 1285 1290
Gln Glu Ala Asp Ser Ala Asn Thr Leu Gln Ile Ala Glu Ile Lys
1295 1300 1305
Glu Lys Ile Gly Thr Arg Ser Ala Glu Asp Pro Val Ser Glu Val
1310 1315 1320
Pro Ala Val Ser Gln His Pro Arg Thr Lys Ser Ser Arg Leu Gln
1325 1330 1335
Gly Ser Ser Leu Ser Ser Glu Ser Ala Arg His Lys Ala Val Glu
1340 1345 1350
Phe Ser Ser Gly Ala Lys Ser Pro Ser Lys Ser Gly Ala Gln Thr
1355 1360 1365
Pro Lys Ser Pro Pro Glu His Tyr Val Gln Glu Thr Pro Leu Met
1370 1375 1380
Phe Ser Arg Cys Thr Ser Val Ser Ser Leu Asp Ser Phe Glu Ser
1385 1390 1395
Arg Ser Ile Ala Ser Ser Val Gln Ser Glu Pro Cys Ser Gly Met
1400 1405 1410
Val Ser Gly Ile Ile Ser Pro Ser Asp Leu Pro Asp Ser Pro Gly
1415 1420 1425
Gln Thr Met Pro Pro Ser Arg Ser Lys Thr Pro Pro Pro Pro Pro
1430 1435 1440
Gln Thr Ala Gln Thr Lys Arg Glu Val Pro Lys Asn Lys Ala Pro
1445 1450 1455
Thr Ala Glu Lys Arg Glu Ser Gly Pro Lys Gln Ala Ala Val Asn
1460 1465 1470
Ala Ala Val Gln Arg Val Gln Val Leu Pro Asp Ala Asp Thr Leu
1475 1480 1485
Leu His Phe Ala Thr Glu Ser Thr Pro Asp Gly Phe Ser Cys Ser
1490 1495 1500
Ser Ser Leu Ser Ala Leu Ser Leu Asp Glu Pro Phe Ile Gln Lys
1505 1510 1515
Asp Val Glu Leu Arg Ile Met Pro Pro Val Gln Glu Asn Asp Asn
1520 1525 1530
Gly Asn Glu Thr Glu Ser Glu Gln Pro Lys Glu Ser Asn Glu Asn
1535 1540 1545
Gln Glu Lys Glu Ala Glu Lys Thr Ile Asp Ser Glu Lys Asp Leu
1550 1555 1560
Leu Asp Asp Ser Asp Asp Asp Asp Ile Glu Ile Leu Glu Glu Cys
1565 1570 1575
Ile Ile Ser Ala Met Pro Thr Lys Ser Ser Arg Lys Ala Lys Lys
1580 1585 1590
Pro Ala Gln Thr Ala Ser Lys Leu Pro Pro Pro Val Ala Arg Lys
1595 1600 1605
Pro Ser Gln Leu Pro Val Tyr Lys Leu Leu Pro Ser Gln Asn Arg
1610 1615 1620
Leu Gln Pro Gln Lys His Val Ser Phe Thr Pro Gly Asp Asp Met
1625 1630 1635
Pro Arg Val Tyr Cys Val Glu Gly Thr Pro Ile Asn Phe Ser Thr
1640 1645 1650
Ala Thr Ser Leu Ser Asp Leu Thr Ile Glu Ser Pro Pro Asn Glu
1655 1660 1665
Leu Ala Ala Gly Glu Gly Val Arg Gly Gly Ala Gln Ser Gly Glu
1670 1675 1680
Phe Glu Lys Arg Asp Thr Ile Pro Thr Glu Gly Arg Ser Thr Asp
1685 1690 1695
Glu Ala Gln Gly Gly Lys Thr Ser Ser Val Thr Ile Pro Glu Leu
1700 1705 1710
Asp Asp Asn Lys Ala Glu Glu Gly Asp Ile Leu Ala Glu Cys Ile
1715 1720 1725
Asn Ser Ala Met Pro Lys Gly Lys Ser His Lys Pro Phe Arg Val
1730 1735 1740
Lys Lys Ile Met Asp Gln Val Gln Gln Ala Ser Ala Ser Ser Ser
1745 1750 1755
Ala Pro Asn Lys Asn Gln Leu Asp Gly Lys Lys Lys Lys Pro Thr
1760 1765 1770
Ser Pro Val Lys Pro Ile Pro Gln Asn Thr Glu Tyr Arg Thr Arg
1775 1780 1785
Val Arg Lys Asn Ala Asp Ser Lys Asn Asn Leu Asn Ala Glu Arg
1790 1795 1800
Val Phe Ser Asp Asn Lys Asp Ser Lys Lys Gln Asn Leu Lys Asn
1805 1810 1815
Asn Ser Lys Val Phe Asn Asp Lys Leu Pro Asn Asn Glu Asp Arg
1820 1825 1830
Val Arg Gly Ser Phe Ala Phe Asp Ser Pro His His Tyr Thr Pro
1835 1840 1845
Ile Glu Gly Thr Pro Tyr Cys Phe Ser Arg Asn Asp Ser Leu Ser
1850 1855 1860
Ser Leu Asp Phe Asp Asp Asp Asp Val Asp Leu Ser Arg Glu Lys
1865 1870 1875
Ala Glu Leu Arg Lys Ala Lys Glu Asn Lys Glu Ser Glu Ala Lys
1880 1885 1890
Val Thr Ser His Thr Glu Leu Thr Ser Asn Gln Gln Ser Ala Asn
1895 1900 1905
Lys Thr Gln Ala Ile Ala Lys Gln Pro Ile Asn Arg Gly Gln Pro
1910 1915 1920
Lys Pro Ile Leu Gln Lys Gln Ser Thr Phe Pro Gln Ser Ser Lys
1925 1930 1935
Asp Ile Pro Asp Arg Gly Ala Ala Thr Asp Glu Lys Leu Gln Asn
1940 1945 1950
Phe Ala Ile Glu Asn Thr Pro Val Cys Phe Ser His Asn Ser Ser
1955 1960 1965
Leu Ser Ser Leu Ser Asp Ile Asp Gln Glu Asn Asn Asn Lys Glu
1970 1975 1980
Asn Glu Pro Ile Lys Glu Thr Glu Pro Pro Asp Ser Gln Gly Glu
1985 1990 1995
Pro Ser Lys Pro Gln Ala Ser Gly Tyr Ala Pro Lys Ser Phe His
2000 2005 2010
Val Glu Asp Thr Pro Val Cys Phe Ser Arg Asn Ser Ser Leu Ser
2015 2020 2025
Ser Leu Ser Ile Asp Ser Glu Asp Asp Leu Leu Gln Glu Cys Ile
2030 2035 2040
Ser Ser Ala Met Pro Lys Lys Lys Lys Pro Ser Arg Leu Lys Gly
2045 2050 2055
Asp Asn Glu Lys His Ser Pro Arg Asn Met Gly Gly Ile Leu Gly
2060 2065 2070
Glu Asp Leu Thr Leu Asp Leu Lys Asp Ile Gln Arg Pro Asp Ser
2075 2080 2085
Glu His Gly Leu Ser Pro Asp Ser Glu Asn Phe Asp Trp Lys Ala
2090 2095 2100
Ile Gln Glu Gly Ala Asn Ser Ile Val Ser Ser Leu His Gln Ala
2105 2110 2115
Ala Ala Ala Ala Cys Leu Ser Arg Gln Ala Ser Ser Asp Ser Asp
2120 2125 2130
Ser Ile Leu Ser Leu Lys Ser Gly Ile Ser Leu Gly Ser Pro Phe
2135 2140 2145
His Leu Thr Pro Asp Gln Glu Glu Lys Pro Phe Thr Ser Asn Lys
2150 2155 2160
Gly Pro Arg Ile Leu Lys Pro Gly Glu Lys Ser Thr Leu Glu Thr
2165 2170 2175
Lys Lys Ile Glu Ser Glu Ser Lys Gly Ile Lys Gly Gly Lys Lys
2180 2185 2190
Val Tyr Lys Ser Leu Ile Thr Gly Lys Val Arg Ser Asn Ser Glu
2195 2200 2205
Ile Ser Gly Gln Met Lys Gln Pro Leu Gln Ala Asn Met Pro Ser
2210 2215 2220
Ile Ser Arg Gly Arg Thr Met Ile His Ile Pro Gly Val Arg Asn
2225 2230 2235
Ser Ser Ser Ser Thr Ser Pro Val Ser Lys Lys Gly Pro Pro Leu
2240 2245 2250
Lys Thr Pro Ala Ser Lys Ser Pro Ser Glu Gly Gln Thr Ala Thr
2255 2260 2265
Thr Ser Pro Arg Gly Ala Lys Pro Ser Val Lys Ser Glu Leu Ser
2270 2275 2280
Pro Val Ala Arg Gln Thr Ser Gln Ile Gly Gly Ser Ser Lys Ala
2285 2290 2295
Pro Ser Arg Ser Gly Ser Arg Asp Ser Thr Pro Ser Arg Pro Ala
2300 2305 2310
Gln Gln Pro Leu Ser Arg Pro Ile Gln Ser Pro Gly Arg Asn Ser
2315 2320 2325
Ile Ser Pro Gly Arg Asn Gly Ile Ser Pro Pro Asn Lys Leu Ser
2330 2335 2340
Gln Leu Pro Arg Thr Ser Ser Pro Ser Thr Ala Ser Thr Lys Ser
2345 2350 2355
Ser Gly Ser Gly Lys Met Ser Tyr Thr Ser Pro Gly Arg Gln Met
2360 2365 2370
Ser Gln Gln Asn Leu Thr Lys Gln Thr Gly Leu Ser Lys Asn Ala
2375 2380 2385
Ser Ser Ile Pro Arg Ser Glu Ser Ala Ser Lys Gly Leu Asn Gln
2390 2395 2400
Met Asn Asn Gly Asn Gly Ala Asn Lys Lys Val Glu Leu Ser Arg
2405 2410 2415
Met Ser Ser Thr Lys Ser Ser Gly Ser Glu Ser Asp Arg Ser Glu
2420 2425 2430
Arg Pro Val Leu Val Arg Gln Ser Thr Phe Ile Lys Glu Ala Pro
2435 2440 2445
Ser Pro Thr Leu Arg Arg Lys Leu Glu Glu Ser Ala Ser Phe Glu
2450 2455 2460
Ser Leu Ser Pro Ser Ser Arg Pro Ala Ser Pro Thr Arg Ser Gln
2465 2470 2475
Ala Gln Thr Pro Val Leu Ser Pro Ser Leu Pro Asp Met Ser Leu
2480 2485 2490
Ser Thr His Ser Ser Val Gln Ala Gly Gly Trp Arg Lys Leu Pro
2495 2500 2505
Pro Asn Leu Ser Pro Thr Ile Glu Tyr Asn Asp Gly Arg Pro Ala
2510 2515 2520
Lys Arg His Asp Ile Ala Arg Ser His Ser Glu Ser Pro Ser Arg
2525 2530 2535
Leu Pro Ile Asn Arg Ser Gly Thr Trp Lys Arg Glu His Ser Lys
2540 2545 2550
His Ser Ser Ser Leu Pro Arg Val Ser Thr Trp Arg Arg Thr Gly
2555 2560 2565
Ser Ser Ser Ser Ile Leu Ser Ala Ser Ser Glu Ser Ser Glu Lys
2570 2575 2580
Ala Lys Ser Glu Asp Glu Lys His Val Asn Ser Ile Ser Gly Thr
2585 2590 2595
Lys Gln Ser Lys Glu Asn Gln Val Ser Ala Lys Gly Thr Trp Arg
2600 2605 2610
Lys Ile Lys Glu Asn Glu Phe Ser Pro Thr Asn Ser Thr Ser Gln
2615 2620 2625
Thr Val Ser Ser Gly Ala Thr Asn Gly Ala Glu Ser Lys Thr Leu
2630 2635 2640
Ile Tyr Gln Met Ala Pro Ala Val Ser Lys Thr Glu Asp Val Trp
2645 2650 2655
Val Arg Ile Glu Asp Cys Pro Ile Asn Asn Pro Arg Ser Gly Arg
2660 2665 2670
Ser Pro Thr Gly Asn Thr Pro Pro Val Ile Asp Ser Val Ser Glu
2675 2680 2685
Lys Ala Asn Pro Asn Ile Lys Asp Ser Lys Asp Asn Gln Ala Lys
2690 2695 2700
Gln Asn Val Gly Asn Gly Ser Val Pro Met Arg Thr Val Gly Leu
2705 2710 2715
Glu Asn Arg Leu Asn Ser Phe Ile Gln Val Asp Ala Pro Asp Gln
2720 2725 2730
Lys Gly Thr Glu Ile Lys Pro Gly Gln Asn Asn Pro Val Pro Val
2735 2740 2745
Ser Glu Thr Asn Glu Ser Ser Ile Val Glu Arg Thr Pro Phe Ser
2750 2755 2760
Ser Ser Ser Ser Ser Lys His Ser Ser Pro Ser Gly Thr Val Ala
2765 2770 2775
Ala Arg Val Thr Pro Phe Asn Tyr Asn Pro Ser Pro Arg Lys Ser
2780 2785 2790
Ser Ala Asp Ser Thr Ser Ala Arg Pro Ser Gln Ile Pro Thr Pro
2795 2800 2805
Val Asn Asn Asn Thr Lys Lys Arg Asp Ser Lys Thr Asp Ser Thr
2810 2815 2820
Glu Ser Ser Gly Thr Gln Ser Pro Lys Arg His Ser Gly Ser Tyr
2825 2830 2835
Leu Val Thr Ser Val
2840
<210> 17
<211> 267
<212> PRT
<213> 智人
<400> 17
Met Lys Ala Ala Val Leu Thr Leu Ala Val Leu Phe Leu Thr Gly Ser
1 5 10 15
Gln Ala Arg His Phe Trp Gln Gln Asp Glu Pro Pro Gln Ser Pro Trp
20 25 30
Asp Arg Val Lys Asp Leu Ala Thr Val Tyr Val Asp Val Leu Lys Asp
35 40 45
Ser Gly Arg Asp Tyr Val Ser Gln Phe Glu Gly Ser Ala Leu Gly Lys
50 55 60
Gln Leu Asn Leu Lys Leu Leu Asp Asn Trp Asp Ser Val Thr Ser Thr
65 70 75 80
Phe Ser Lys Leu Arg Glu Gln Leu Gly Pro Val Thr Gln Glu Phe Trp
85 90 95
Asp Asn Leu Glu Lys Glu Thr Glu Gly Leu Arg Gln Glu Met Ser Lys
100 105 110
Asp Leu Glu Glu Val Lys Ala Lys Val Gln Pro Tyr Leu Asp Asp Phe
115 120 125
Gln Lys Lys Trp Gln Glu Glu Met Glu Leu Tyr Arg Gln Lys Val Glu
130 135 140
Pro Leu Arg Ala Glu Leu Gln Glu Gly Ala Arg Gln Lys Leu His Glu
145 150 155 160
Leu Gln Glu Lys Leu Ser Pro Leu Gly Glu Glu Met Arg Asp Arg Ala
165 170 175
Arg Ala His Val Asp Ala Leu Arg Thr His Leu Ala Pro Tyr Ser Asp
180 185 190
Glu Leu Arg Gln Arg Leu Ala Ala Arg Leu Glu Ala Leu Lys Glu Asn
195 200 205
Gly Gly Ala Arg Leu Ala Glu Tyr His Ala Lys Ala Thr Glu His Leu
210 215 220
Ser Thr Leu Ser Glu Lys Ala Lys Pro Ala Leu Glu Asp Leu Arg Gln
225 230 235 240
Gly Leu Leu Pro Val Leu Glu Ser Phe Lys Val Ser Phe Leu Ser Ala
245 250 255
Leu Glu Glu Tyr Thr Lys Lys Leu Asn Thr Gln
260 265
<210> 18
<211> 83
<212> PRT
<213> 智人
<400> 18
Met Arg Leu Phe Leu Ser Leu Pro Val Leu Val Val Val Leu Ser Ile
1 5 10 15
Val Leu Glu Gly Pro Ala Pro Ala Gln Gly Thr Pro Asp Val Ser Ser
20 25 30
Ala Leu Asp Lys Leu Lys Glu Phe Gly Asn Thr Leu Glu Asp Lys Ala
35 40 45
Arg Glu Leu Ile Ser Arg Ile Lys Gln Ser Glu Leu Ser Ala Lys Met
50 55 60
Arg Glu Trp Phe Ser Glu Thr Phe Gln Lys Val Lys Glu Lys Leu Lys
65 70 75 80
Ile Asp Ser
<210> 19
<211> 345
<212> PRT
<213> 智人
<400> 19
Met Ile Ser Pro Val Leu Ile Leu Phe Ser Ser Phe Leu Cys His Val
1 5 10 15
Ala Ile Ala Gly Arg Thr Cys Pro Lys Pro Asp Asp Leu Pro Phe Ser
20 25 30
Thr Val Val Pro Leu Lys Thr Phe Tyr Glu Pro Gly Glu Glu Ile Thr
35 40 45
Tyr Ser Cys Lys Pro Gly Tyr Val Ser Arg Gly Gly Met Arg Lys Phe
50 55 60
Ile Cys Pro Leu Thr Gly Leu Trp Pro Ile Asn Thr Leu Lys Cys Thr
65 70 75 80
Pro Arg Val Cys Pro Phe Ala Gly Ile Leu Glu Asn Gly Ala Val Arg
85 90 95
Tyr Thr Thr Phe Glu Tyr Pro Asn Thr Ile Ser Phe Ser Cys Asn Thr
100 105 110
Gly Phe Tyr Leu Asn Gly Ala Asp Ser Ala Lys Cys Thr Glu Glu Gly
115 120 125
Lys Trp Ser Pro Glu Leu Pro Val Cys Ala Pro Ile Ile Cys Pro Pro
130 135 140
Pro Ser Ile Pro Thr Phe Ala Thr Leu Arg Val Tyr Lys Pro Ser Ala
145 150 155 160
Gly Asn Asn Ser Leu Tyr Arg Asp Thr Ala Val Phe Glu Cys Leu Pro
165 170 175
Gln His Ala Met Phe Gly Asn Asp Thr Ile Thr Cys Thr Thr His Gly
180 185 190
Asn Trp Thr Lys Leu Pro Glu Cys Arg Glu Val Lys Cys Pro Phe Pro
195 200 205
Ser Arg Pro Asp Asn Gly Phe Val Asn Tyr Pro Ala Lys Pro Thr Leu
210 215 220
Tyr Tyr Lys Asp Lys Ala Thr Phe Gly Cys His Asp Gly Tyr Ser Leu
225 230 235 240
Asp Gly Pro Glu Glu Ile Glu Cys Thr Lys Leu Gly Asn Trp Ser Ala
245 250 255
Met Pro Ser Cys Lys Ala Ser Cys Lys Val Pro Val Lys Lys Ala Thr
260 265 270
Val Val Tyr Gln Gly Glu Arg Val Lys Ile Gln Glu Lys Phe Lys Asn
275 280 285
Gly Met Leu His Gly Asp Lys Val Ser Phe Phe Cys Lys Asn Lys Glu
290 295 300
Lys Lys Cys Ser Tyr Thr Glu Asp Ala Gln Cys Ile Asp Gly Thr Ile
305 310 315 320
Glu Val Pro Lys Cys Phe Lys Glu His Ser Ser Leu Ala Phe Trp Lys
325 330 335
Thr Asp Ala Ser Asp Val Lys Pro Cys
340 345
<210> 20
<211> 204
<212> PRT
<213> 智人
<400> 20
Met Ala Glu Gln Glu Pro Thr Ala Glu Gln Leu Ala Gln Ile Ala Ala
1 5 10 15
Glu Asn Glu Glu Asp Glu His Ser Val Asn Tyr Lys Pro Pro Ala Gln
20 25 30
Lys Ser Ile Gln Glu Ile Gln Glu Leu Asp Lys Asp Asp Glu Ser Leu
35 40 45
Arg Lys Tyr Lys Glu Ala Leu Leu Gly Arg Val Ala Val Ser Ala Asp
50 55 60
Pro Asn Val Pro Asn Val Val Val Thr Gly Leu Thr Leu Val Cys Ser
65 70 75 80
Ser Ala Pro Gly Pro Leu Glu Leu Asp Leu Thr Gly Asp Leu Glu Ser
85 90 95
Phe Lys Lys Gln Ser Phe Val Leu Lys Glu Gly Val Glu Tyr Arg Ile
100 105 110
Lys Ile Ser Phe Arg Val Asn Arg Glu Ile Val Ser Gly Met Lys Tyr
115 120 125
Ile Gln His Thr Tyr Arg Lys Gly Val Lys Ile Asp Lys Thr Asp Tyr
130 135 140
Met Val Gly Ser Tyr Gly Pro Arg Ala Glu Glu Tyr Glu Phe Leu Thr
145 150 155 160
Pro Val Glu Glu Ala Pro Lys Gly Met Leu Ala Arg Gly Ser Tyr Ser
165 170 175
Ile Lys Ser Arg Phe Thr Asp Asp Asp Lys Thr Asp His Leu Ser Trp
180 185 190
Glu Trp Asn Leu Thr Ile Lys Lys Asp Trp Lys Asp
195 200
<210> 21
<211> 529
<212> PRT
<213> 智人
<400> 21
Met Leu Gly Phe Val Gly Arg Val Ala Ala Ala Pro Ala Ser Gly Ala
1 5 10 15
Leu Arg Arg Leu Thr Pro Ser Ala Ser Leu Pro Pro Ala Gln Leu Leu
20 25 30
Leu Arg Ala Ala Pro Thr Ala Val His Pro Val Arg Asp Tyr Ala Ala
35 40 45
Gln Thr Ser Pro Ser Pro Lys Ala Gly Ala Ala Thr Gly Arg Ile Val
50 55 60
Ala Val Ile Gly Ala Val Val Asp Val Gln Phe Asp Glu Gly Leu Pro
65 70 75 80
Pro Ile Leu Asn Ala Leu Glu Val Gln Gly Arg Glu Thr Arg Leu Val
85 90 95
Leu Glu Val Ala Gln His Leu Gly Glu Ser Thr Val Arg Thr Ile Ala
100 105 110
Met Asp Gly Thr Glu Gly Leu Val Arg Gly Gln Lys Val Leu Asp Ser
115 120 125
Gly Ala Pro Ile Lys Ile Pro Val Gly Pro Glu Thr Leu Gly Arg Ile
130 135 140
Met Asn Val Ile Gly Glu Pro Ile Asp Glu Arg Gly Pro Ile Lys Thr
145 150 155 160
Lys Gln Phe Ala Pro Ile His Ala Glu Ala Pro Glu Phe Met Glu Met
165 170 175
Ser Val Glu Gln Glu Ile Leu Val Thr Gly Ile Lys Val Val Asp Leu
180 185 190
Leu Ala Pro Tyr Ala Lys Gly Gly Lys Ile Gly Leu Phe Gly Gly Ala
195 200 205
Gly Val Gly Lys Thr Val Leu Ile Met Glu Leu Ile Asn Asn Val Ala
210 215 220
Lys Ala His Gly Gly Tyr Ser Val Phe Ala Gly Val Gly Glu Arg Thr
225 230 235 240
Arg Glu Gly Asn Asp Leu Tyr His Glu Met Ile Glu Ser Gly Val Ile
245 250 255
Asn Leu Lys Asp Ala Thr Ser Lys Val Ala Leu Val Tyr Gly Gln Met
260 265 270
Asn Glu Pro Pro Gly Ala Arg Ala Arg Val Ala Leu Thr Gly Leu Thr
275 280 285
Val Ala Glu Tyr Phe Arg Asp Gln Glu Gly Gln Asp Val Leu Leu Phe
290 295 300
Ile Asp Asn Ile Phe Arg Phe Thr Gln Ala Gly Ser Glu Val Ser Ala
305 310 315 320
Leu Leu Gly Arg Ile Pro Ser Ala Val Gly Tyr Gln Pro Thr Leu Ala
325 330 335
Thr Asp Met Gly Thr Met Gln Glu Arg Ile Thr Thr Thr Lys Lys Gly
340 345 350
Ser Ile Thr Ser Val Gln Ala Ile Tyr Val Pro Ala Asp Asp Leu Thr
355 360 365
Asp Pro Ala Pro Ala Thr Thr Phe Ala His Leu Asp Ala Thr Thr Val
370 375 380
Leu Ser Arg Ala Ile Ala Glu Leu Gly Ile Tyr Pro Ala Val Asp Pro
385 390 395 400
Leu Asp Ser Thr Ser Arg Ile Met Asp Pro Asn Ile Val Gly Ser Glu
405 410 415
His Tyr Asp Val Ala Arg Gly Val Gln Lys Ile Leu Gln Asp Tyr Lys
420 425 430
Ser Leu Gln Asp Ile Ile Ala Ile Leu Gly Met Asp Glu Leu Ser Glu
435 440 445
Glu Asp Lys Leu Thr Val Ser Arg Ala Arg Lys Ile Gln Arg Phe Leu
450 455 460
Ser Gln Pro Phe Gln Val Ala Glu Val Phe Thr Gly His Met Gly Lys
465 470 475 480
Leu Val Pro Leu Lys Glu Thr Ile Lys Gly Phe Gln Gln Ile Leu Ala
485 490 495
Gly Glu Tyr Asp His Leu Pro Glu Gln Ala Phe Tyr Met Val Gly Pro
500 505 510
Ile Glu Glu Ala Val Ala Lys Ala Asp Lys Leu Ala Glu Glu His Ser
515 520 525
Ser
<210> 22
<211> 785
<212> PRT
<213> 智人
<400> 22
Met Leu Pro Ala Ala Pro Gly Lys Gly Leu Gly Ser Pro Asp Pro Ala
1 5 10 15
Pro Cys Gly Pro Ala Pro Pro Gly Asn Thr Lys Asp Ile Ile Met Ile
20 25 30
Tyr Glu Glu Asp Ala Glu Glu Trp Ala Leu Tyr Leu Thr Glu Val Phe
35 40 45
Leu His Val Val Lys Arg Glu Ala Ile Leu Leu Tyr Arg Leu Glu Asn
50 55 60
Phe Ser Phe Arg His Leu Glu Leu Leu Asn Leu Thr Ser Tyr Lys Cys
65 70 75 80
Lys Leu Leu Ile Leu Ser Asn Ser Leu Leu Arg Asp Leu Thr Pro Lys
85 90 95
Lys Cys Gln Phe Leu Glu Lys Ile Leu His Ser Pro Lys Ser Val Val
100 105 110
Thr Leu Leu Cys Gly Val Lys Ser Ser Asp Gln Leu Tyr Glu Leu Leu
115 120 125
Asn Ile Ser Gln Ser Arg Trp Glu Ile Ser Thr Glu Gln Glu Pro Glu
130 135 140
Asp Tyr Ile Ser Val Ile Gln Ser Ile Ile Phe Lys Asp Ser Glu Asp
145 150 155 160
Tyr Phe Glu Val Asn Ile Pro Thr Asp Leu Arg Ala Lys His Ser Gly
165 170 175
Glu Ile Ser Glu Arg Lys Glu Ile Glu Glu Leu Ser Glu Ala Ser Arg
180 185 190
Asn Thr Ile Pro Leu Ala Val Val Leu Pro Thr Glu Ile Pro Cys Glu
195 200 205
Asn Pro Gly Glu Ile Phe Ile Ile Leu Arg Asp Glu Val Ile Gly Asp
210 215 220
Thr Val Glu Val Glu Phe Thr Ser Ser Asn Lys Arg Ile Arg Thr Arg
225 230 235 240
Pro Ala Leu Trp Asn Lys Lys Val Trp Cys Met Lys Ala Leu Glu Phe
245 250 255
Pro Ala Gly Ser Val His Val Asn Val Tyr Cys Asp Gly Ile Val Lys
260 265 270
Ala Thr Thr Lys Ile Lys Tyr Tyr Pro Thr Ala Lys Ala Lys Glu Cys
275 280 285
Leu Phe Arg Met Ala Asp Ser Gly Glu Ser Leu Cys Gln Asn Ser Ile
290 295 300
Glu Glu Leu Asp Gly Val Leu Thr Ser Ile Phe Lys His Glu Ile Pro
305 310 315 320
Tyr Tyr Glu Phe Gln Ser Leu Gln Thr Glu Ile Cys Ser Gln Asn Lys
325 330 335
Tyr Thr His Phe Lys Glu Leu Pro Thr Leu Leu His Cys Ala Ala Lys
340 345 350
Phe Gly Leu Lys Asn Leu Ala Ile His Leu Leu Gln Cys Ser Gly Ala
355 360 365
Thr Trp Ala Ser Lys Met Lys Asn Met Glu Gly Ser Asp Pro Ala His
370 375 380
Ile Ala Glu Arg His Gly His Lys Glu Leu Lys Lys Ile Phe Glu Asp
385 390 395 400
Phe Ser Ile Gln Glu Ile Asp Ile Asn Asn Glu Gln Glu Asn Asp Tyr
405 410 415
Glu Glu Asp Ile Ala Ser Phe Ser Thr Tyr Ile Pro Ser Thr Gln Asn
420 425 430
Pro Ala Phe His His Glu Ser Arg Lys Thr Tyr Gly Gln Ser Ala Asp
435 440 445
Gly Ala Glu Ala Asn Glu Met Glu Gly Glu Gly Lys Gln Asn Gly Ser
450 455 460
Gly Met Glu Thr Lys His Ser Pro Leu Glu Val Gly Ser Glu Ser Ser
465 470 475 480
Glu Asp Gln Tyr Asp Asp Leu Tyr Val Phe Ile Pro Gly Ala Asp Pro
485 490 495
Glu Asn Asn Ser Gln Glu Pro Leu Met Ser Ser Arg Pro Pro Leu Pro
500 505 510
Pro Pro Arg Pro Val Ala Asn Ala Phe Gln Leu Glu Arg Pro His Phe
515 520 525
Thr Leu Pro Gly Thr Met Val Glu Gly Gln Met Glu Arg Ser Gln Asn
530 535 540
Trp Gly His Pro Gly Val Arg Gln Glu Thr Gly Asp Glu Pro Lys Gly
545 550 555 560
Glu Lys Glu Lys Lys Glu Glu Glu Lys Glu Gln Glu Glu Glu Glu Asp
565 570 575
Pro Tyr Thr Phe Ala Glu Ile Asp Asp Ser Glu Tyr Asp Met Ile Leu
580 585 590
Ala Asn Leu Ser Ile Lys Lys Lys Thr Gly Ser Arg Ser Phe Ile Ile
595 600 605
Asn Arg Pro Pro Ala Pro Thr Pro Arg Pro Thr Ser Ile Pro Pro Lys
610 615 620
Glu Glu Thr Thr Pro Tyr Ile Ala Gln Val Phe Gln Gln Lys Thr Ala
625 630 635 640
Arg Arg Gln Ser Asp Asp Asp Lys Phe Cys Gly Leu Pro Lys Lys Gln
645 650 655
Asp Arg Ala Arg Ile Glu Ser Pro Ala Phe Ser Thr Leu Arg Gly Cys
660 665 670
Leu Thr Asp Gly Gln Glu Glu Leu Ile Leu Leu Gln Glu Lys Val Lys
675 680 685
Asn Gly Lys Met Ser Met Asp Glu Ala Leu Glu Lys Phe Lys His Trp
690 695 700
Gln Met Gly Lys Ser Gly Leu Glu Met Ile Gln Gln Glu Lys Leu Arg
705 710 715 720
Gln Leu Arg Asp Cys Ile Ile Gly Lys Arg Pro Glu Glu Glu Asn Val
725 730 735
Tyr Asn Lys Leu Thr Ile Val His His Pro Gly Gly Lys Glu Thr Ala
740 745 750
His Asn Glu Asn Lys Phe Tyr Asn Val His Phe Ser Asn Lys Leu Pro
755 760 765
Ala Arg Pro Gln Val Glu Lys Glu Phe Gly Phe Cys Cys Lys Lys Asp
770 775 780
His
785
<210> 23
<211> 657
<212> PRT
<213> 智人
<400> 23
Met Gly Glu Glu Asp Tyr Tyr Leu Glu Leu Cys Glu Arg Pro Val Gln
1 5 10 15
Phe Glu Lys Ala Asn Pro Val Asn Cys Val Phe Phe Asp Glu Ala Asn
20 25 30
Lys Gln Val Phe Ala Val Arg Ser Gly Gly Ala Thr Gly Val Val Val
35 40 45
Lys Gly Pro Asp Asp Arg Asn Pro Ile Ser Phe Arg Met Asp Asp Lys
50 55 60
Gly Glu Val Lys Cys Ile Lys Phe Ser Leu Glu Asn Lys Ile Leu Ala
65 70 75 80
Val Gln Arg Thr Ser Lys Thr Val Asp Phe Cys Asn Phe Ile Pro Asp
85 90 95
Asn Ser Gln Leu Glu Tyr Thr Gln Glu Cys Lys Thr Lys Asn Ala Asn
100 105 110
Ile Leu Gly Phe Cys Trp Thr Ser Ser Thr Glu Ile Val Phe Ile Thr
115 120 125
Asp Gln Gly Ile Glu Phe Tyr Gln Val Leu Pro Glu Lys Arg Ser Leu
130 135 140
Lys Leu Leu Lys Ser His Asn Leu Asn Val Asn Trp Tyr Met Tyr Cys
145 150 155 160
Pro Glu Ser Ala Val Ile Leu Leu Ser Thr Thr Val Leu Glu Asn Val
165 170 175
Leu Gln Pro Phe His Phe Arg Ala Gly Thr Met Ser Lys Leu Pro Lys
180 185 190
Phe Glu Ile Glu Leu Pro Ala Ala Pro Lys Ser Thr Lys Pro Ser Leu
195 200 205
Ser Glu Arg Asp Ile Ala Met Ala Thr Ile Tyr Gly Gln Leu Tyr Val
210 215 220
Leu Phe Leu Arg His His Ser Arg Thr Ser Asn Ser Thr Gly Ala Glu
225 230 235 240
Val Val Leu Tyr His Leu Pro Arg Glu Gly Ala Cys Lys Lys Met His
245 250 255
Ile Leu Lys Leu Asn Arg Thr Gly Lys Phe Ala Leu Asn Val Val Asp
260 265 270
Asn Leu Val Val Val His His Gln Asp Thr Glu Thr Ser Val Ile Phe
275 280 285
Asp Ile Lys Leu Arg Gly Glu Phe Asp Gly Ser Val Thr Phe His His
290 295 300
Pro Val Leu Pro Ala Arg Ser Ile Gln Pro Tyr Gln Ile Pro Ile Thr
305 310 315 320
Gly Pro Ala Ala Val Thr Ser Gln Ser Pro Val Pro Cys Lys Leu Tyr
325 330 335
Ser Ser Ser Trp Ile Val Phe Gln Pro Asp Ile Ile Ile Ser Ala Ser
340 345 350
Gln Gly Tyr Leu Trp Asn Leu Gln Val Lys Leu Glu Pro Ile Val Asn
355 360 365
Leu Leu Pro Asp Lys Gly Arg Leu Met Asp Phe Leu Leu Gln Arg Lys
370 375 380
Glu Cys Lys Met Val Ile Leu Ser Val Cys Ser Gln Met Leu Ser Glu
385 390 395 400
Ser Asp Arg Ala Ser Leu Pro Val Ile Ala Thr Val Phe Asp Lys Leu
405 410 415
Asn His Glu Tyr Lys Lys Tyr Leu Asp Ala Glu Gln Ser Tyr Ala Met
420 425 430
Ala Val Glu Ala Gly Gln Ser Arg Ser Ser Pro Leu Leu Lys Arg Pro
435 440 445
Val Arg Thr Gln Ala Val Leu Asp Gln Ser Asp Val Tyr Thr His Val
450 455 460
Leu Ser Ala Phe Val Glu Lys Lys Glu Met Pro His Lys Phe Val Ile
465 470 475 480
Ala Val Leu Met Glu Tyr Ile Arg Ser Leu Asn Gln Phe Gln Ile Ala
485 490 495
Val Gln His Tyr Leu His Glu Leu Val Ile Lys Thr Leu Val Gln His
500 505 510
Asn Leu Phe Tyr Met Leu His Gln Phe Leu Gln Tyr His Val Leu Ser
515 520 525
Asp Ser Lys Pro Leu Ala Cys Leu Leu Leu Ser Leu Glu Ser Phe Tyr
530 535 540
Pro Pro Ala His Gln Leu Ser Leu Asp Met Leu Lys Arg Leu Ser Thr
545 550 555 560
Ala Asn Asp Glu Ile Val Glu Val Leu Leu Ser Lys His Gln Val Leu
565 570 575
Ala Ala Leu Arg Phe Ile Arg Gly Ile Gly Gly His Asp Asn Ile Ser
580 585 590
Ala Arg Lys Phe Leu Asp Ala Ala Lys Gln Thr Glu Asp Asn Met Leu
595 600 605
Phe Tyr Thr Ile Phe Arg Phe Phe Glu Gln Arg Asn Gln Arg Leu Arg
610 615 620
Gly Ser Pro Asn Phe Thr Pro Gly Glu His Cys Glu Glu His Val Ala
625 630 635 640
Phe Phe Lys Gln Ile Phe Gly Asp Gln Ala Leu Met Arg Pro Thr Thr
645 650 655
Phe
<210> 24
<211> 126
<212> PRT
<213> 智人
<400> 24
Met Pro Ser Ser Thr Leu Thr Cys Lys Pro Phe Asp Leu Lys Gln Arg
1 5 10 15
Ser Ser Arg Arg Gly Pro Lys Ser Thr Ala Ser Ala Ser Pro Arg Ser
20 25 30
Cys Leu Lys Pro Ser Cys Gly Lys Gln Val Cys Leu Leu Leu Ser Val
35 40 45
Arg Arg Ser Gln Ser Leu Ala His Pro Gly Arg Asp Ser Thr Arg Val
50 55 60
Leu Ser Tyr Gln Gln Thr Ser Ser Asp Ala Val Ser Gln Tyr Lys His
65 70 75 80
Thr Gly Lys Val Glu Glu Leu Tyr Gly Leu Arg Leu Ser Trp Leu Ser
85 90 95
Gln Ala Gln Phe Leu Leu Ala Gln Asp Lys Thr Ala Tyr Ala Val Lys
100 105 110
Ser Val Val Leu Pro Ala Ser Asn His Lys Thr Lys Gly Gln
115 120 125
<210> 25
<211> 1663
<212> PRT
<213> 智人
<400> 25
Met Gly Pro Thr Ser Gly Pro Ser Leu Leu Leu Leu Leu Leu Thr His
1 5 10 15
Leu Pro Leu Ala Leu Gly Ser Pro Met Tyr Ser Ile Ile Thr Pro Asn
20 25 30
Ile Leu Arg Leu Glu Ser Glu Glu Thr Met Val Leu Glu Ala His Asp
35 40 45
Ala Gln Gly Asp Val Pro Val Thr Val Thr Val His Asp Phe Pro Gly
50 55 60
Lys Lys Leu Val Leu Ser Ser Glu Lys Thr Val Leu Thr Pro Ala Thr
65 70 75 80
Asn His Met Gly Asn Val Thr Phe Thr Ile Pro Ala Asn Arg Glu Phe
85 90 95
Lys Ser Glu Lys Gly Arg Asn Lys Phe Val Thr Val Gln Ala Thr Phe
100 105 110
Gly Thr Gln Val Val Glu Lys Val Val Leu Val Ser Leu Gln Ser Gly
115 120 125
Tyr Leu Phe Ile Gln Thr Asp Lys Thr Ile Tyr Thr Pro Gly Ser Thr
130 135 140
Val Leu Tyr Arg Ile Phe Thr Val Asn His Lys Leu Leu Pro Val Gly
145 150 155 160
Arg Thr Val Met Val Asn Ile Glu Asn Pro Glu Gly Ile Pro Val Lys
165 170 175
Gln Asp Ser Leu Ser Ser Gln Asn Gln Leu Gly Val Leu Pro Leu Ser
180 185 190
Trp Asp Ile Pro Glu Leu Val Asn Met Gly Gln Trp Lys Ile Arg Ala
195 200 205
Tyr Tyr Glu Asn Ser Pro Gln Gln Val Phe Ser Thr Glu Phe Glu Val
210 215 220
Lys Glu Tyr Val Leu Pro Ser Phe Glu Val Ile Val Glu Pro Thr Glu
225 230 235 240
Lys Phe Tyr Tyr Ile Tyr Asn Glu Lys Gly Leu Glu Val Thr Ile Thr
245 250 255
Ala Arg Phe Leu Tyr Gly Lys Lys Val Glu Gly Thr Ala Phe Val Ile
260 265 270
Phe Gly Ile Gln Asp Gly Glu Gln Arg Ile Ser Leu Pro Glu Ser Leu
275 280 285
Lys Arg Ile Pro Ile Glu Asp Gly Ser Gly Glu Val Val Leu Ser Arg
290 295 300
Lys Val Leu Leu Asp Gly Val Gln Asn Pro Arg Ala Glu Asp Leu Val
305 310 315 320
Gly Lys Ser Leu Tyr Val Ser Ala Thr Val Ile Leu His Ser Gly Ser
325 330 335
Asp Met Val Gln Ala Glu Arg Ser Gly Ile Pro Ile Val Thr Ser Pro
340 345 350
Tyr Gln Ile His Phe Thr Lys Thr Pro Lys Tyr Phe Lys Pro Gly Met
355 360 365
Pro Phe Asp Leu Met Val Phe Val Thr Asn Pro Asp Gly Ser Pro Ala
370 375 380
Tyr Arg Val Pro Val Ala Val Gln Gly Glu Asp Thr Val Gln Ser Leu
385 390 395 400
Thr Gln Gly Asp Gly Val Ala Lys Leu Ser Ile Asn Thr His Pro Ser
405 410 415
Gln Lys Pro Leu Ser Ile Thr Val Arg Thr Lys Lys Gln Glu Leu Ser
420 425 430
Glu Ala Glu Gln Ala Thr Arg Thr Met Gln Ala Leu Pro Tyr Ser Thr
435 440 445
Val Gly Asn Ser Asn Asn Tyr Leu His Leu Ser Val Leu Arg Thr Glu
450 455 460
Leu Arg Pro Gly Glu Thr Leu Asn Val Asn Phe Leu Leu Arg Met Asp
465 470 475 480
Arg Ala His Glu Ala Lys Ile Arg Tyr Tyr Thr Tyr Leu Ile Met Asn
485 490 495
Lys Gly Arg Leu Leu Lys Ala Gly Arg Gln Val Arg Glu Pro Gly Gln
500 505 510
Asp Leu Val Val Leu Pro Leu Ser Ile Thr Thr Asp Phe Ile Pro Ser
515 520 525
Phe Arg Leu Val Ala Tyr Tyr Thr Leu Ile Gly Ala Ser Gly Gln Arg
530 535 540
Glu Val Val Ala Asp Ser Val Trp Val Asp Val Lys Asp Ser Cys Val
545 550 555 560
Gly Ser Leu Val Val Lys Ser Gly Gln Ser Glu Asp Arg Gln Pro Val
565 570 575
Pro Gly Gln Gln Met Thr Leu Lys Ile Glu Gly Asp His Gly Ala Arg
580 585 590
Val Val Leu Val Ala Val Asp Lys Gly Val Phe Val Leu Asn Lys Lys
595 600 605
Asn Lys Leu Thr Gln Ser Lys Ile Trp Asp Val Val Glu Lys Ala Asp
610 615 620
Ile Gly Cys Thr Pro Gly Ser Gly Lys Asp Tyr Ala Gly Val Phe Ser
625 630 635 640
Asp Ala Gly Leu Thr Phe Thr Ser Ser Ser Gly Gln Gln Thr Ala Gln
645 650 655
Arg Ala Glu Leu Gln Cys Pro Gln Pro Ala Ala Arg Arg Arg Arg Ser
660 665 670
Val Gln Leu Thr Glu Lys Arg Met Asp Lys Val Gly Lys Tyr Pro Lys
675 680 685
Glu Leu Arg Lys Cys Cys Glu Asp Gly Met Arg Glu Asn Pro Met Arg
690 695 700
Phe Ser Cys Gln Arg Arg Thr Arg Phe Ile Ser Leu Gly Glu Ala Cys
705 710 715 720
Lys Lys Val Phe Leu Asp Cys Cys Asn Tyr Ile Thr Glu Leu Arg Arg
725 730 735
Gln His Ala Arg Ala Ser His Leu Gly Leu Ala Arg Ser Asn Leu Asp
740 745 750
Glu Asp Ile Ile Ala Glu Glu Asn Ile Val Ser Arg Ser Glu Phe Pro
755 760 765
Glu Ser Trp Leu Trp Asn Val Glu Asp Leu Lys Glu Pro Pro Lys Asn
770 775 780
Gly Ile Ser Thr Lys Leu Met Asn Ile Phe Leu Lys Asp Ser Ile Thr
785 790 795 800
Thr Trp Glu Ile Leu Ala Val Ser Met Ser Asp Lys Lys Gly Ile Cys
805 810 815
Val Ala Asp Pro Phe Glu Val Thr Val Met Gln Asp Phe Phe Ile Asp
820 825 830
Leu Arg Leu Pro Tyr Ser Val Val Arg Asn Glu Gln Val Glu Ile Arg
835 840 845
Ala Val Leu Tyr Asn Tyr Arg Gln Asn Gln Glu Leu Lys Val Arg Val
850 855 860
Glu Leu Leu His Asn Pro Ala Phe Cys Ser Leu Ala Thr Thr Lys Arg
865 870 875 880
Arg His Gln Gln Thr Val Thr Ile Pro Pro Lys Ser Ser Leu Ser Val
885 890 895
Pro Tyr Val Ile Val Pro Leu Lys Thr Gly Leu Gln Glu Val Glu Val
900 905 910
Lys Ala Ala Val Tyr His His Phe Ile Ser Asp Gly Val Arg Lys Ser
915 920 925
Leu Lys Val Val Pro Glu Gly Ile Arg Met Asn Lys Thr Val Ala Val
930 935 940
Arg Thr Leu Asp Pro Glu Arg Leu Gly Arg Glu Gly Val Gln Lys Glu
945 950 955 960
Asp Ile Pro Pro Ala Asp Leu Ser Asp Gln Val Pro Asp Thr Glu Ser
965 970 975
Glu Thr Arg Ile Leu Leu Gln Gly Thr Pro Val Ala Gln Met Thr Glu
980 985 990
Asp Ala Val Asp Ala Glu Arg Leu Lys His Leu Ile Val Thr Pro Ser
995 1000 1005
Gly Cys Gly Glu Gln Asn Met Ile Gly Met Thr Pro Thr Val Ile
1010 1015 1020
Ala Val His Tyr Leu Asp Glu Thr Glu Gln Trp Glu Lys Phe Gly
1025 1030 1035
Leu Glu Lys Arg Gln Gly Ala Leu Glu Leu Ile Lys Lys Gly Tyr
1040 1045 1050
Thr Gln Gln Leu Ala Phe Arg Gln Pro Ser Ser Ala Phe Ala Ala
1055 1060 1065
Phe Val Lys Arg Ala Pro Ser Thr Trp Leu Thr Ala Tyr Val Val
1070 1075 1080
Lys Val Phe Ser Leu Ala Val Asn Leu Ile Ala Ile Asp Ser Gln
1085 1090 1095
Val Leu Cys Gly Ala Val Lys Trp Leu Ile Leu Glu Lys Gln Lys
1100 1105 1110
Pro Asp Gly Val Phe Gln Glu Asp Ala Pro Val Ile His Gln Glu
1115 1120 1125
Met Ile Gly Gly Leu Arg Asn Asn Asn Glu Lys Asp Met Ala Leu
1130 1135 1140
Thr Ala Phe Val Leu Ile Ser Leu Gln Glu Ala Lys Asp Ile Cys
1145 1150 1155
Glu Glu Gln Val Asn Ser Leu Pro Gly Ser Ile Thr Lys Ala Gly
1160 1165 1170
Asp Phe Leu Glu Ala Asn Tyr Met Asn Leu Gln Arg Ser Tyr Thr
1175 1180 1185
Val Ala Ile Ala Gly Tyr Ala Leu Ala Gln Met Gly Arg Leu Lys
1190 1195 1200
Gly Pro Leu Leu Asn Lys Phe Leu Thr Thr Ala Lys Asp Lys Asn
1205 1210 1215
Arg Trp Glu Asp Pro Gly Lys Gln Leu Tyr Asn Val Glu Ala Thr
1220 1225 1230
Ser Tyr Ala Leu Leu Ala Leu Leu Gln Leu Lys Asp Phe Asp Phe
1235 1240 1245
Val Pro Pro Val Val Arg Trp Leu Asn Glu Gln Arg Tyr Tyr Gly
1250 1255 1260
Gly Gly Tyr Gly Ser Thr Gln Ala Thr Phe Met Val Phe Gln Ala
1265 1270 1275
Leu Ala Gln Tyr Gln Lys Asp Ala Pro Asp His Gln Glu Leu Asn
1280 1285 1290
Leu Asp Val Ser Leu Gln Leu Pro Ser Arg Ser Ser Lys Ile Thr
1295 1300 1305
His Arg Ile His Trp Glu Ser Ala Ser Leu Leu Arg Ser Glu Glu
1310 1315 1320
Thr Lys Glu Asn Glu Gly Phe Thr Val Thr Ala Glu Gly Lys Gly
1325 1330 1335
Gln Gly Thr Leu Ser Val Val Thr Met Tyr His Ala Lys Ala Lys
1340 1345 1350
Asp Gln Leu Thr Cys Asn Lys Phe Asp Leu Lys Val Thr Ile Lys
1355 1360 1365
Pro Ala Pro Glu Thr Glu Lys Arg Pro Gln Asp Ala Lys Asn Thr
1370 1375 1380
Met Ile Leu Glu Ile Cys Thr Arg Tyr Arg Gly Asp Gln Asp Ala
1385 1390 1395
Thr Met Ser Ile Leu Asp Ile Ser Met Met Thr Gly Phe Ala Pro
1400 1405 1410
Asp Thr Asp Asp Leu Lys Gln Leu Ala Asn Gly Val Asp Arg Tyr
1415 1420 1425
Ile Ser Lys Tyr Glu Leu Asp Lys Ala Phe Ser Asp Arg Asn Thr
1430 1435 1440
Leu Ile Ile Tyr Leu Asp Lys Val Ser His Ser Glu Asp Asp Cys
1445 1450 1455
Leu Ala Phe Lys Val His Gln Tyr Phe Asn Val Glu Leu Ile Gln
1460 1465 1470
Pro Gly Ala Val Lys Val Tyr Ala Tyr Tyr Asn Leu Glu Glu Ser
1475 1480 1485
Cys Thr Arg Phe Tyr His Pro Glu Lys Glu Asp Gly Lys Leu Asn
1490 1495 1500
Lys Leu Cys Arg Asp Glu Leu Cys Arg Cys Ala Glu Glu Asn Cys
1505 1510 1515
Phe Ile Gln Lys Ser Asp Asp Lys Val Thr Leu Glu Glu Arg Leu
1520 1525 1530
Asp Lys Ala Cys Glu Pro Gly Val Asp Tyr Val Tyr Lys Thr Arg
1535 1540 1545
Leu Val Lys Val Gln Leu Ser Asn Asp Phe Asp Glu Tyr Ile Met
1550 1555 1560
Ala Ile Glu Gln Thr Ile Lys Ser Gly Ser Asp Glu Val Gln Val
1565 1570 1575
Gly Gln Gln Arg Thr Phe Ile Ser Pro Ile Lys Cys Arg Glu Ala
1580 1585 1590
Leu Lys Leu Glu Glu Lys Lys His Tyr Leu Met Trp Gly Leu Ser
1595 1600 1605
Ser Asp Phe Trp Gly Glu Lys Pro Asn Leu Ser Tyr Ile Ile Gly
1610 1615 1620
Lys Asp Thr Trp Val Glu His Trp Pro Glu Glu Asp Glu Cys Gln
1625 1630 1635
Asp Glu Glu Asn Gln Lys Gln Cys Gln Asp Leu Gly Ala Phe Thr
1640 1645 1650
Glu Ser Met Val Val Phe Gly Cys Pro Asn
1655 1660
<210> 26
<211> 559
<212> PRT
<213> 智人
<400> 26
Met Ser Ala Cys Arg Ser Phe Ala Val Ala Ile Cys Ile Leu Glu Ile
1 5 10 15
Ser Ile Leu Thr Ala Gln Tyr Thr Thr Ser Tyr Asp Pro Glu Leu Thr
20 25 30
Glu Ser Ser Gly Ser Ala Ser His Ile Asp Cys Arg Met Ser Pro Trp
35 40 45
Ser Glu Trp Ser Gln Cys Asp Pro Cys Leu Arg Gln Met Phe Arg Ser
50 55 60
Arg Ser Ile Glu Val Phe Gly Gln Phe Asn Gly Lys Arg Cys Thr Asp
65 70 75 80
Ala Val Gly Asp Arg Arg Gln Cys Val Pro Thr Glu Pro Cys Glu Asp
85 90 95
Ala Glu Asp Asp Cys Gly Asn Asp Phe Gln Cys Ser Thr Gly Arg Cys
100 105 110
Ile Lys Met Arg Leu Arg Cys Asn Gly Asp Asn Asp Cys Gly Asp Phe
115 120 125
Ser Asp Glu Asp Asp Cys Glu Ser Glu Pro Arg Pro Pro Cys Arg Asp
130 135 140
Arg Val Val Glu Glu Ser Glu Leu Ala Arg Thr Ala Gly Tyr Gly Ile
145 150 155 160
Asn Ile Leu Gly Met Asp Pro Leu Ser Thr Pro Phe Asp Asn Glu Phe
165 170 175
Tyr Asn Gly Leu Cys Asn Arg Asp Arg Asp Gly Asn Thr Leu Thr Tyr
180 185 190
Tyr Arg Arg Pro Trp Asn Val Ala Ser Leu Ile Tyr Glu Thr Lys Gly
195 200 205
Glu Lys Asn Phe Arg Thr Glu His Tyr Glu Glu Gln Ile Glu Ala Phe
210 215 220
Lys Ser Ile Ile Gln Glu Lys Thr Ser Asn Phe Asn Ala Ala Ile Ser
225 230 235 240
Leu Lys Phe Thr Pro Thr Glu Thr Asn Lys Ala Glu Gln Cys Cys Glu
245 250 255
Glu Thr Ala Ser Ser Ile Ser Leu His Gly Lys Gly Ser Phe Arg Phe
260 265 270
Ser Tyr Ser Lys Asn Glu Thr Tyr Gln Leu Phe Leu Ser Tyr Ser Ser
275 280 285
Lys Lys Glu Lys Met Phe Leu His Val Lys Gly Glu Ile His Leu Gly
290 295 300
Arg Phe Val Met Arg Asn Arg Asp Val Val Leu Thr Thr Thr Phe Val
305 310 315 320
Asp Asp Ile Lys Ala Leu Pro Thr Thr Tyr Glu Lys Gly Glu Tyr Phe
325 330 335
Ala Phe Leu Glu Thr Tyr Gly Thr His Tyr Ser Ser Ser Gly Ser Leu
340 345 350
Gly Gly Leu Tyr Glu Leu Ile Tyr Val Leu Asp Lys Ala Ser Met Lys
355 360 365
Arg Lys Gly Val Glu Leu Lys Asp Ile Lys Arg Cys Leu Gly Tyr His
370 375 380
Leu Asp Val Ser Leu Ala Phe Ser Glu Ile Ser Val Gly Ala Glu Phe
385 390 395 400
Asn Lys Asp Asp Cys Val Lys Arg Gly Glu Gly Arg Ala Val Asn Ile
405 410 415
Thr Ser Glu Asn Leu Ile Asp Asp Val Val Ser Leu Ile Arg Gly Gly
420 425 430
Thr Arg Lys Tyr Ala Phe Glu Leu Lys Glu Lys Leu Leu Arg Gly Thr
435 440 445
Val Ile Asp Val Thr Asp Phe Val Asn Trp Ala Ser Ser Ile Asn Asp
450 455 460
Ala Pro Val Leu Ile Ser Gln Lys Leu Ser Pro Ile Tyr Asn Leu Val
465 470 475 480
Pro Val Lys Met Lys Asn Ala His Leu Lys Lys Gln Asn Leu Glu Arg
485 490 495
Ala Ile Glu Asp Tyr Ile Asn Glu Phe Ser Val Arg Lys Cys His Thr
500 505 510
Cys Gln Asn Gly Gly Thr Val Ile Leu Met Asp Gly Lys Cys Leu Cys
515 520 525
Ala Cys Pro Phe Lys Phe Glu Gly Ile Ala Cys Glu Ile Ser Lys Gln
530 535 540
Lys Ile Ser Glu Gly Leu Pro Ala Leu Glu Phe Pro Asn Glu Lys
545 550 555
<210> 27
<211> 261
<212> PRT
<213> 智人
<400> 27
Met Ala Ser Pro Asp Trp Gly Tyr Asp Asp Lys Asn Gly Pro Glu Gln
1 5 10 15
Trp Ser Lys Leu Tyr Pro Ile Ala Asn Gly Asn Asn Gln Ser Pro Val
20 25 30
Asp Ile Lys Thr Ser Glu Thr Lys His Asp Thr Ser Leu Lys Pro Ile
35 40 45
Ser Val Ser Tyr Asn Pro Ala Thr Ala Lys Glu Ile Ile Asn Val Gly
50 55 60
His Ser Phe His Val Asn Phe Glu Asp Asn Asp Asn Arg Ser Val Leu
65 70 75 80
Lys Gly Gly Pro Phe Ser Asp Ser Tyr Arg Leu Phe Gln Phe His Phe
85 90 95
His Trp Gly Ser Thr Asn Glu His Gly Ser Glu His Thr Val Asp Gly
100 105 110
Val Lys Tyr Ser Ala Glu Leu His Val Ala His Trp Asn Ser Ala Lys
115 120 125
Tyr Ser Ser Leu Ala Glu Ala Ala Ser Lys Ala Asp Gly Leu Ala Val
130 135 140
Ile Gly Val Leu Met Lys Val Gly Glu Ala Asn Pro Lys Leu Gln Lys
145 150 155 160
Val Leu Asp Ala Leu Gln Ala Ile Lys Thr Lys Gly Lys Arg Ala Pro
165 170 175
Phe Thr Asn Phe Asp Pro Ser Thr Leu Leu Pro Ser Ser Leu Asp Phe
180 185 190
Trp Thr Tyr Pro Gly Ser Leu Thr His Pro Pro Leu Tyr Glu Ser Val
195 200 205
Thr Trp Ile Ile Cys Lys Glu Ser Ile Ser Val Ser Ser Glu Gln Leu
210 215 220
Ala Gln Phe Arg Ser Leu Leu Ser Asn Val Glu Gly Asp Asn Ala Val
225 230 235 240
Pro Met Gln His Asn Asn Arg Pro Thr Gln Pro Leu Lys Gly Arg Thr
245 250 255
Val Arg Ala Ser Phe
260
<210> 28
<211> 260
<212> PRT
<213> 智人
<400> 28
Met Ser His His Trp Gly Tyr Gly Lys His Asn Gly Pro Glu His Trp
1 5 10 15
His Lys Asp Phe Pro Ile Ala Lys Gly Glu Arg Gln Ser Pro Val Asp
20 25 30
Ile Asp Thr His Thr Ala Lys Tyr Asp Pro Ser Leu Lys Pro Leu Ser
35 40 45
Val Ser Tyr Asp Gln Ala Thr Ser Leu Arg Ile Leu Asn Asn Gly His
50 55 60
Ala Phe Asn Val Glu Phe Asp Asp Ser Gln Asp Lys Ala Val Leu Lys
65 70 75 80
Gly Gly Pro Leu Asp Gly Thr Tyr Arg Leu Ile Gln Phe His Phe His
85 90 95
Trp Gly Ser Leu Asp Gly Gln Gly Ser Glu His Thr Val Asp Lys Lys
100 105 110
Lys Tyr Ala Ala Glu Leu His Leu Val His Trp Asn Thr Lys Tyr Gly
115 120 125
Asp Phe Gly Lys Ala Val Gln Gln Pro Asp Gly Leu Ala Val Leu Gly
130 135 140
Ile Phe Leu Lys Val Gly Ser Ala Lys Pro Gly Leu Gln Lys Val Val
145 150 155 160
Asp Val Leu Asp Ser Ile Lys Thr Lys Gly Lys Ser Ala Asp Phe Thr
165 170 175
Asn Phe Asp Pro Arg Gly Leu Leu Pro Glu Ser Leu Asp Tyr Trp Thr
180 185 190
Tyr Pro Gly Ser Leu Thr Thr Pro Pro Leu Leu Glu Cys Val Thr Trp
195 200 205
Ile Val Leu Lys Glu Pro Ile Ser Val Ser Ser Glu Gln Val Leu Lys
210 215 220
Phe Arg Lys Leu Asn Phe Asn Gly Glu Gly Glu Pro Glu Glu Leu Met
225 230 235 240
Val Asp Asn Trp Arg Pro Ala Gln Pro Leu Lys Asn Arg Gln Ile Lys
245 250 255
Ala Ser Phe Lys
260
<210> 29
<211> 417
<212> PRT
<213> 智人
<400> 29
Met Leu Leu Ser Val Pro Leu Leu Leu Gly Leu Leu Gly Leu Ala Val
1 5 10 15
Ala Glu Pro Ala Val Tyr Phe Lys Glu Gln Phe Leu Asp Gly Asp Gly
20 25 30
Trp Thr Ser Arg Trp Ile Glu Ser Lys His Lys Ser Asp Phe Gly Lys
35 40 45
Phe Val Leu Ser Ser Gly Lys Phe Tyr Gly Asp Glu Glu Lys Asp Lys
50 55 60
Gly Leu Gln Thr Ser Gln Asp Ala Arg Phe Tyr Ala Leu Ser Ala Ser
65 70 75 80
Phe Glu Pro Phe Ser Asn Lys Gly Gln Thr Leu Val Val Gln Phe Thr
85 90 95
Val Lys His Glu Gln Asn Ile Asp Cys Gly Gly Gly Tyr Val Lys Leu
100 105 110
Phe Pro Asn Ser Leu Asp Gln Thr Asp Met His Gly Asp Ser Glu Tyr
115 120 125
Asn Ile Met Phe Gly Pro Asp Ile Cys Gly Pro Gly Thr Lys Lys Val
130 135 140
His Val Ile Phe Asn Tyr Lys Gly Lys Asn Val Leu Ile Asn Lys Asp
145 150 155 160
Ile Arg Cys Lys Asp Asp Glu Phe Thr His Leu Tyr Thr Leu Ile Val
165 170 175
Arg Pro Asp Asn Thr Tyr Glu Val Lys Ile Asp Asn Ser Gln Val Glu
180 185 190
Ser Gly Ser Leu Glu Asp Asp Trp Asp Phe Leu Pro Pro Lys Lys Ile
195 200 205
Lys Asp Pro Asp Ala Ser Lys Pro Glu Asp Trp Asp Glu Arg Ala Lys
210 215 220
Ile Asp Asp Pro Thr Asp Ser Lys Pro Glu Asp Trp Asp Lys Pro Glu
225 230 235 240
His Ile Pro Asp Pro Asp Ala Lys Lys Pro Glu Asp Trp Asp Glu Glu
245 250 255
Met Asp Gly Glu Trp Glu Pro Pro Val Ile Gln Asn Pro Glu Tyr Lys
260 265 270
Gly Glu Trp Lys Pro Arg Gln Ile Asp Asn Pro Asp Tyr Lys Gly Thr
275 280 285
Trp Ile His Pro Glu Ile Asp Asn Pro Glu Tyr Ser Pro Asp Pro Ser
290 295 300
Ile Tyr Ala Tyr Asp Asn Phe Gly Val Leu Gly Leu Asp Leu Trp Gln
305 310 315 320
Val Lys Ser Gly Thr Ile Phe Asp Asn Phe Leu Ile Thr Asn Asp Glu
325 330 335
Ala Tyr Ala Glu Glu Phe Gly Asn Glu Thr Trp Gly Val Thr Lys Ala
340 345 350
Ala Glu Lys Gln Met Lys Asp Lys Gln Asp Glu Glu Gln Arg Leu Lys
355 360 365
Glu Glu Glu Glu Asp Lys Lys Arg Lys Glu Glu Glu Glu Ala Glu Asp
370 375 380
Lys Glu Asp Asp Glu Asp Lys Asp Glu Asp Glu Glu Asp Glu Glu Asp
385 390 395 400
Lys Glu Glu Asp Glu Glu Glu Asp Val Pro Gly Gln Ala Lys Asp Glu
405 410 415
Leu
<210> 30
<211> 348
<212> PRT
<213> 智人
<400> 30
Met Tyr Thr Ala Ile Pro Gln Ser Gly Ser Pro Phe Pro Gly Ser Val
1 5 10 15
Gln Asp Pro Gly Leu His Val Trp Arg Val Glu Lys Leu Lys Pro Val
20 25 30
Pro Val Ala Gln Glu Asn Gln Gly Val Phe Phe Ser Gly Asp Ser Tyr
35 40 45
Leu Val Leu His Asn Gly Pro Glu Glu Val Ser His Leu His Leu Trp
50 55 60
Ile Gly Gln Gln Ser Ser Arg Asp Glu Gln Gly Ala Cys Ala Val Leu
65 70 75 80
Ala Val His Leu Asn Thr Leu Leu Gly Glu Arg Pro Val Gln His Arg
85 90 95
Glu Val Gln Gly Asn Glu Ser Asp Leu Phe Met Ser Tyr Phe Pro Arg
100 105 110
Gly Leu Lys Tyr Gln Glu Gly Gly Val Glu Ser Ala Phe His Lys Thr
115 120 125
Ser Thr Gly Ala Pro Ala Ala Ile Lys Lys Leu Tyr Gln Val Lys Gly
130 135 140
Lys Lys Asn Ile Arg Ala Thr Glu Arg Ala Leu Asn Trp Asp Ser Phe
145 150 155 160
Asn Thr Gly Asp Cys Phe Ile Leu Asp Leu Gly Gln Asn Ile Phe Ala
165 170 175
Trp Cys Gly Gly Lys Ser Asn Ile Leu Glu Arg Asn Lys Ala Arg Asp
180 185 190
Leu Ala Leu Ala Ile Arg Asp Ser Glu Arg Gln Gly Lys Ala Gln Val
195 200 205
Glu Ile Val Thr Asp Gly Glu Glu Pro Ala Glu Met Ile Gln Val Leu
210 215 220
Gly Pro Lys Pro Ala Leu Lys Glu Gly Asn Pro Glu Glu Asp Leu Thr
225 230 235 240
Ala Asp Lys Ala Asn Ala Gln Ala Ala Ala Leu Tyr Lys Val Ser Asp
245 250 255
Ala Thr Gly Gln Met Asn Leu Thr Lys Val Ala Asp Ser Ser Pro Phe
260 265 270
Ala Leu Glu Leu Leu Ile Ser Asp Asp Cys Phe Val Leu Asp Asn Gly
275 280 285
Leu Cys Gly Lys Ile Tyr Ile Trp Lys Gly Arg Lys Ala Asn Glu Lys
290 295 300
Glu Arg Gln Ala Ala Leu Gln Val Ala Glu Gly Phe Ile Ser Arg Met
305 310 315 320
Gln Tyr Ala Pro Asn Thr Gln Val Glu Ile Leu Pro Gln Gly His Glu
325 330 335
Ser Pro Ile Phe Lys Gln Phe Phe Lys Asp Trp Lys
340 345
<210> 31
<211> 80
<212> PRT
<213> 智人
<400> 31
Met Gly Arg Ala Met Val Ala Arg Leu Gly Leu Gly Leu Leu Leu Leu
1 5 10 15
Ala Leu Leu Leu Pro Thr Gln Ile Tyr Ser Ser Glu Thr Thr Thr Gly
20 25 30
Thr Ser Ser Asn Ser Ser Gln Ser Thr Ser Asn Thr Gly Leu Ala Pro
35 40 45
Asn Pro Thr Asn Ala Thr Thr Lys Ala Ala Gly Gly Ala Leu Gln Ser
50 55 60
Thr Ala Ser Leu Phe Val Val Ser Leu Ser Leu Leu His Leu Tyr Ser
65 70 75 80
<210> 32
<211> 238
<212> PRT
<213> 智人
<400> 32
Met Ala Val Glu Gly Gly Met Lys Cys Val Lys Phe Leu Leu Tyr Val
1 5 10 15
Leu Leu Leu Ala Phe Cys Ala Cys Ala Val Gly Leu Ile Ala Val Gly
20 25 30
Val Gly Ala Gln Leu Val Leu Ser Gln Thr Ile Ile Gln Gly Ala Thr
35 40 45
Pro Gly Ser Leu Leu Pro Val Val Ile Ile Ala Val Gly Val Phe Leu
50 55 60
Phe Leu Val Ala Phe Val Gly Cys Cys Gly Ala Cys Lys Glu Asn Tyr
65 70 75 80
Cys Leu Met Ile Thr Phe Ala Ile Phe Leu Ser Leu Ile Met Leu Val
85 90 95
Glu Val Ala Ala Ala Ile Ala Gly Tyr Val Phe Arg Asp Lys Val Met
100 105 110
Ser Glu Phe Asn Asn Asn Phe Arg Gln Gln Met Glu Asn Tyr Pro Lys
115 120 125
Asn Asn His Thr Ala Ser Ile Leu Asp Arg Met Gln Ala Asp Phe Lys
130 135 140
Cys Cys Gly Ala Ala Asn Tyr Thr Asp Trp Glu Lys Ile Pro Ser Met
145 150 155 160
Ser Lys Asn Arg Val Pro Asp Ser Cys Cys Ile Asn Val Thr Val Gly
165 170 175
Cys Gly Ile Asn Phe Asn Glu Lys Ala Ile His Lys Glu Gly Cys Val
180 185 190
Glu Lys Ile Gly Gly Trp Leu Arg Lys Asn Val Leu Val Val Ala Ala
195 200 205
Ala Ala Leu Gly Ile Ala Phe Val Glu Val Leu Gly Ile Val Phe Ala
210 215 220
Cys Cys Leu Val Lys Ser Ile Arg Ser Gly Tyr Glu Val Met
225 230 235
<210> 33
<211> 146
<212> PRT
<213> 智人
<400> 33
Met Ala Gln Lys Arg Pro Ala Cys Thr Leu Lys Pro Glu Cys Val Gln
1 5 10 15
Gln Leu Leu Val Cys Ser Gln Glu Ala Lys Lys Ser Ala Tyr Cys Pro
20 25 30
Tyr Ser His Phe Pro Val Gly Ala Ala Leu Leu Thr Gln Glu Gly Arg
35 40 45
Ile Phe Lys Gly Cys Asn Ile Glu Asn Ala Cys Tyr Pro Leu Gly Ile
50 55 60
Cys Ala Glu Arg Thr Ala Ile Gln Lys Ala Val Ser Glu Gly Tyr Lys
65 70 75 80
Asp Phe Arg Ala Ile Ala Ile Ala Ser Asp Met Gln Asp Asp Phe Ile
85 90 95
Ser Pro Cys Gly Ala Cys Arg Gln Val Met Arg Glu Phe Gly Thr Asn
100 105 110
Trp Pro Val Tyr Met Thr Lys Pro Asp Gly Thr Tyr Ile Val Met Thr
115 120 125
Val Gln Glu Leu Leu Pro Ser Ser Phe Gly Pro Glu Asp Leu Gln Lys
130 135 140
Thr Gln
145
<210> 34
<211> 252
<212> PRT
<213> 智人
<400> 34
Met Gly Pro Pro Ser Ala Ser Pro His Arg Glu Cys Ile Pro Trp Gln
1 5 10 15
Gly Leu Leu Leu Thr Ala Ser Leu Leu Asn Phe Trp Asn Pro Pro Thr
20 25 30
Thr Ala Lys Leu Thr Ile Glu Ser Met Pro Leu Ser Val Ala Glu Gly
35 40 45
Lys Glu Val Leu Leu Leu Val His Asn Leu Pro Gln His Leu Phe Gly
50 55 60
Tyr Ser Trp Tyr Lys Gly Glu Arg Val Asp Gly Asn Ser Leu Ile Val
65 70 75 80
Gly Tyr Val Ile Gly Thr Gln Gln Ala Thr Pro Gly Ala Ala Tyr Ser
85 90 95
Gly Arg Glu Thr Ile Tyr Thr Asn Ala Ser Leu Leu Ile Gln Asn Val
100 105 110
Thr Gln Asn Asp Ile Gly Phe Tyr Thr Leu Gln Val Ile Lys Ser Asp
115 120 125
Leu Val Asn Glu Glu Ala Thr Gly Gln Phe His Val Tyr Gln Glu Asn
130 135 140
Ala Pro Gly Leu Pro Val Gly Ala Val Ala Gly Ile Val Thr Gly Val
145 150 155 160
Leu Val Gly Val Ala Leu Val Ala Ala Leu Val Cys Phe Leu Leu Leu
165 170 175
Ala Lys Thr Gly Arg Thr Ser Ile Gln Arg Asp Leu Lys Glu Gln Gln
180 185 190
Pro Gln Ala Leu Ala Pro Gly Arg Gly Pro Ser His Ser Ser Ala Phe
195 200 205
Ser Met Ser Pro Leu Ser Thr Ala Gln Ala Pro Leu Pro Asn Pro Arg
210 215 220
Thr Ala Ala Ser Ile Tyr Glu Glu Leu Leu Lys His Asp Thr Asn Ile
225 230 235 240
Tyr Cys Arg Met Asp His Lys Ala Glu Val Ala Ser
245 250
<210> 35
<211> 702
<212> PRT
<213> 智人
<400> 35
Met Glu Ser Pro Ser Ala Pro Pro His Arg Trp Cys Ile Pro Trp Gln
1 5 10 15
Arg Leu Leu Leu Thr Ala Ser Leu Leu Thr Phe Trp Asn Pro Pro Thr
20 25 30
Thr Ala Lys Leu Thr Ile Glu Ser Thr Pro Phe Asn Val Ala Glu Gly
35 40 45
Lys Glu Val Leu Leu Leu Val His Asn Leu Pro Gln His Leu Phe Gly
50 55 60
Tyr Ser Trp Tyr Lys Gly Glu Arg Val Asp Gly Asn Arg Gln Ile Ile
65 70 75 80
Gly Tyr Val Ile Gly Thr Gln Gln Ala Thr Pro Gly Pro Ala Tyr Ser
85 90 95
Gly Arg Glu Ile Ile Tyr Pro Asn Ala Ser Leu Leu Ile Gln Asn Ile
100 105 110
Ile Gln Asn Asp Thr Gly Phe Tyr Thr Leu His Val Ile Lys Ser Asp
115 120 125
Leu Val Asn Glu Glu Ala Thr Gly Gln Phe Arg Val Tyr Pro Glu Leu
130 135 140
Pro Lys Pro Ser Ile Ser Ser Asn Asn Ser Lys Pro Val Glu Asp Lys
145 150 155 160
Asp Ala Val Ala Phe Thr Cys Glu Pro Glu Thr Gln Asp Ala Thr Tyr
165 170 175
Leu Trp Trp Val Asn Asn Gln Ser Leu Pro Val Ser Pro Arg Leu Gln
180 185 190
Leu Ser Asn Gly Asn Arg Thr Leu Thr Leu Phe Asn Val Thr Arg Asn
195 200 205
Asp Thr Ala Ser Tyr Lys Cys Glu Thr Gln Asn Pro Val Ser Ala Arg
210 215 220
Arg Ser Asp Ser Val Ile Leu Asn Val Leu Tyr Gly Pro Asp Ala Pro
225 230 235 240
Thr Ile Ser Pro Leu Asn Thr Ser Tyr Arg Ser Gly Glu Asn Leu Asn
245 250 255
Leu Ser Cys His Ala Ala Ser Asn Pro Pro Ala Gln Tyr Ser Trp Phe
260 265 270
Val Asn Gly Thr Phe Gln Gln Ser Thr Gln Glu Leu Phe Ile Pro Asn
275 280 285
Ile Thr Val Asn Asn Ser Gly Ser Tyr Thr Cys Gln Ala His Asn Ser
290 295 300
Asp Thr Gly Leu Asn Arg Thr Thr Val Thr Thr Ile Thr Val Tyr Ala
305 310 315 320
Glu Pro Pro Lys Pro Phe Ile Thr Ser Asn Asn Ser Asn Pro Val Glu
325 330 335
Asp Glu Asp Ala Val Ala Leu Thr Cys Glu Pro Glu Ile Gln Asn Thr
340 345 350
Thr Tyr Leu Trp Trp Val Asn Asn Gln Ser Leu Pro Val Ser Pro Arg
355 360 365
Leu Gln Leu Ser Asn Asp Asn Arg Thr Leu Thr Leu Leu Ser Val Thr
370 375 380
Arg Asn Asp Val Gly Pro Tyr Glu Cys Gly Ile Gln Asn Lys Leu Ser
385 390 395 400
Val Asp His Ser Asp Pro Val Ile Leu Asn Val Leu Tyr Gly Pro Asp
405 410 415
Asp Pro Thr Ile Ser Pro Ser Tyr Thr Tyr Tyr Arg Pro Gly Val Asn
420 425 430
Leu Ser Leu Ser Cys His Ala Ala Ser Asn Pro Pro Ala Gln Tyr Ser
435 440 445
Trp Leu Ile Asp Gly Asn Ile Gln Gln His Thr Gln Glu Leu Phe Ile
450 455 460
Ser Asn Ile Thr Glu Lys Asn Ser Gly Leu Tyr Thr Cys Gln Ala Asn
465 470 475 480
Asn Ser Ala Ser Gly His Ser Arg Thr Thr Val Lys Thr Ile Thr Val
485 490 495
Ser Ala Glu Leu Pro Lys Pro Ser Ile Ser Ser Asn Asn Ser Lys Pro
500 505 510
Val Glu Asp Lys Asp Ala Val Ala Phe Thr Cys Glu Pro Glu Ala Gln
515 520 525
Asn Thr Thr Tyr Leu Trp Trp Val Asn Gly Gln Ser Leu Pro Val Ser
530 535 540
Pro Arg Leu Gln Leu Ser Asn Gly Asn Arg Thr Leu Thr Leu Phe Asn
545 550 555 560
Val Thr Arg Asn Asp Ala Arg Ala Tyr Val Cys Gly Ile Gln Asn Ser
565 570 575
Val Ser Ala Asn Arg Ser Asp Pro Val Thr Leu Asp Val Leu Tyr Gly
580 585 590
Pro Asp Thr Pro Ile Ile Ser Pro Pro Asp Ser Ser Tyr Leu Ser Gly
595 600 605
Ala Asn Leu Asn Leu Ser Cys His Ser Ala Ser Asn Pro Ser Pro Gln
610 615 620
Tyr Ser Trp Arg Ile Asn Gly Ile Pro Gln Gln His Thr Gln Val Leu
625 630 635 640
Phe Ile Ala Lys Ile Thr Pro Asn Asn Asn Gly Thr Tyr Ala Cys Phe
645 650 655
Val Ser Asn Leu Ala Thr Gly Arg Asn Asn Ser Ile Val Lys Ser Ile
660 665 670
Thr Val Ser Ala Ser Gly Thr Ser Pro Gly Leu Ser Ala Gly Ala Thr
675 680 685
Val Gly Ile Met Ile Gly Val Leu Val Gly Val Ala Leu Ile
690 695 700
<210> 36
<211> 344
<212> PRT
<213> 智人
<400> 36
Met Gly Pro Pro Ser Ala Pro Pro Cys Arg Leu His Val Pro Trp Lys
1 5 10 15
Glu Val Leu Leu Thr Ala Ser Leu Leu Thr Phe Trp Asn Pro Pro Thr
20 25 30
Thr Ala Lys Leu Thr Ile Glu Ser Thr Pro Phe Asn Val Ala Glu Gly
35 40 45
Lys Glu Val Leu Leu Leu Ala His Asn Leu Pro Gln Asn Arg Ile Gly
50 55 60
Tyr Ser Trp Tyr Lys Gly Glu Arg Val Asp Gly Asn Ser Leu Ile Val
65 70 75 80
Gly Tyr Val Ile Gly Thr Gln Gln Ala Thr Pro Gly Pro Ala Tyr Ser
85 90 95
Gly Arg Glu Thr Ile Tyr Pro Asn Ala Ser Leu Leu Ile Gln Asn Val
100 105 110
Thr Gln Asn Asp Thr Gly Phe Tyr Thr Leu Gln Val Ile Lys Ser Asp
115 120 125
Leu Val Asn Glu Glu Ala Thr Gly Gln Phe His Val Tyr Pro Glu Leu
130 135 140
Pro Lys Pro Ser Ile Ser Ser Asn Asn Ser Asn Pro Val Glu Asp Lys
145 150 155 160
Asp Ala Val Ala Phe Thr Cys Glu Pro Glu Val Gln Asn Thr Thr Tyr
165 170 175
Leu Trp Trp Val Asn Gly Gln Ser Leu Pro Val Ser Pro Arg Leu Gln
180 185 190
Leu Ser Asn Gly Asn Met Thr Leu Thr Leu Leu Ser Val Lys Arg Asn
195 200 205
Asp Ala Gly Ser Tyr Glu Cys Glu Ile Gln Asn Pro Ala Ser Ala Asn
210 215 220
Arg Ser Asp Pro Val Thr Leu Asn Val Leu Tyr Gly Pro Asp Gly Pro
225 230 235 240
Thr Ile Ser Pro Ser Lys Ala Asn Tyr Arg Pro Gly Glu Asn Leu Asn
245 250 255
Leu Ser Cys His Ala Ala Ser Asn Pro Pro Ala Gln Tyr Ser Trp Phe
260 265 270
Ile Asn Gly Thr Phe Gln Gln Ser Thr Gln Glu Leu Phe Ile Pro Asn
275 280 285
Ile Thr Val Asn Asn Ser Gly Ser Tyr Met Cys Gln Ala His Asn Ser
290 295 300
Ala Thr Gly Leu Asn Arg Thr Thr Val Thr Met Ile Thr Val Ser Gly
305 310 315 320
Ser Ala Pro Val Leu Ser Ala Val Ala Thr Val Gly Ile Thr Ile Gly
325 330 335
Val Leu Ala Arg Val Ala Leu Ile
340
<210> 37
<211> 165
<212> PRT
<213> 智人
<400> 37
Met Glu Met Phe Gln Gly Leu Leu Leu Leu Leu Leu Leu Ser Met Gly
1 5 10 15
Gly Thr Trp Ala Ser Lys Glu Pro Leu Arg Pro Arg Cys Arg Pro Ile
20 25 30
Asn Ala Thr Leu Ala Val Glu Lys Glu Gly Cys Pro Val Cys Ile Thr
35 40 45
Val Asn Thr Thr Ile Cys Ala Gly Tyr Cys Pro Thr Met Thr Arg Val
50 55 60
Leu Gln Gly Val Leu Pro Ala Leu Pro Gln Val Val Cys Asn Tyr Arg
65 70 75 80
Asp Val Arg Phe Glu Ser Ile Arg Leu Pro Gly Cys Pro Arg Gly Val
85 90 95
Asn Pro Val Val Ser Tyr Ala Val Ala Leu Ser Cys Gln Cys Ala Leu
100 105 110
Cys Arg Arg Ser Thr Thr Asp Cys Gly Gly Pro Lys Asp His Pro Leu
115 120 125
Thr Cys Asp Asp Pro Arg Phe Gln Asp Ser Ser Ser Ser Lys Ala Pro
130 135 140
Pro Pro Ser Leu Pro Ser Pro Ser Arg Leu Pro Gly Pro Ser Asp Thr
145 150 155 160
Pro Ile Leu Pro Gln
165
<210> 38
<211> 383
<212> PRT
<213> 智人
<400> 38
Met Gly Val Lys Ala Ser Gln Thr Gly Phe Val Val Leu Val Leu Leu
1 5 10 15
Gln Cys Cys Ser Ala Tyr Lys Leu Val Cys Tyr Tyr Thr Ser Trp Ser
20 25 30
Gln Tyr Arg Glu Gly Asp Gly Ser Cys Phe Pro Asp Ala Leu Asp Arg
35 40 45
Phe Leu Cys Thr His Ile Ile Tyr Ser Phe Ala Asn Ile Ser Asn Asp
50 55 60
His Ile Asp Thr Trp Glu Trp Asn Asp Val Thr Leu Tyr Gly Met Leu
65 70 75 80
Asn Thr Leu Lys Asn Arg Asn Pro Asn Leu Lys Thr Leu Leu Ser Val
85 90 95
Gly Gly Trp Asn Phe Gly Ser Gln Arg Phe Ser Lys Ile Ala Ser Asn
100 105 110
Thr Gln Ser Arg Arg Thr Phe Ile Lys Ser Val Pro Pro Phe Leu Arg
115 120 125
Thr His Gly Phe Asp Gly Leu Asp Leu Ala Trp Leu Tyr Pro Gly Arg
130 135 140
Arg Asp Lys Gln His Phe Thr Thr Leu Ile Lys Glu Met Lys Ala Glu
145 150 155 160
Phe Ile Lys Glu Ala Gln Pro Gly Lys Lys Gln Leu Leu Leu Ser Ala
165 170 175
Ala Leu Ser Ala Gly Lys Val Thr Ile Asp Ser Ser Tyr Asp Ile Ala
180 185 190
Lys Ile Ser Gln His Leu Asp Phe Ile Ser Ile Met Thr Tyr Asp Phe
195 200 205
His Gly Ala Trp Arg Gly Thr Thr Gly His His Ser Pro Leu Phe Arg
210 215 220
Gly Gln Glu Asp Ala Ser Pro Asp Arg Phe Ser Asn Thr Asp Tyr Ala
225 230 235 240
Val Gly Tyr Met Leu Arg Leu Gly Ala Pro Ala Ser Lys Leu Val Met
245 250 255
Gly Ile Pro Thr Phe Gly Arg Ser Phe Thr Leu Ala Ser Ser Glu Thr
260 265 270
Gly Val Gly Ala Pro Ile Ser Gly Pro Gly Ile Pro Gly Arg Phe Thr
275 280 285
Lys Glu Ala Gly Thr Leu Ala Tyr Tyr Glu Ile Cys Asp Phe Leu Arg
290 295 300
Gly Ala Thr Val His Arg Ile Leu Gly Gln Gln Val Pro Tyr Ala Thr
305 310 315 320
Lys Gly Asn Gln Trp Val Gly Tyr Asp Asp Gln Glu Ser Val Lys Ser
325 330 335
Lys Val Gln Tyr Leu Lys Asp Arg Gln Leu Ala Gly Ala Met Val Trp
340 345 350
Ala Leu Asp Leu Asp Asp Phe Gln Gly Ser Phe Cys Gly Gln Asp Leu
355 360 365
Arg Phe Pro Leu Thr Asn Ala Ile Lys Asp Ala Leu Ala Ala Thr
370 375 380
<210> 39
<211> 381
<212> PRT
<213> 智人
<400> 39
Met Pro Phe Ser Asn Ser His Asn Ala Leu Lys Leu Arg Phe Pro Ala
1 5 10 15
Glu Asp Glu Phe Pro Asp Leu Ser Ala His Asn Asn His Met Ala Lys
20 25 30
Val Leu Thr Pro Glu Leu Tyr Ala Glu Leu Arg Ala Lys Ser Thr Pro
35 40 45
Ser Gly Phe Thr Leu Asp Asp Val Ile Gln Thr Gly Val Asp Asn Pro
50 55 60
Gly His Pro Tyr Ile Met Thr Val Gly Cys Val Ala Gly Asp Glu Glu
65 70 75 80
Ser Tyr Glu Val Phe Lys Asp Leu Phe Asp Pro Ile Ile Glu Asp Arg
85 90 95
His Gly Gly Tyr Lys Pro Ser Asp Glu His Lys Thr Asp Leu Asn Pro
100 105 110
Asp Asn Leu Gln Gly Gly Asp Asp Leu Asp Pro Asn Tyr Val Leu Ser
115 120 125
Ser Arg Val Arg Thr Gly Arg Ser Ile Arg Gly Phe Cys Leu Pro Pro
130 135 140
His Cys Ser Arg Gly Glu Arg Arg Ala Ile Glu Lys Leu Ala Val Glu
145 150 155 160
Ala Leu Ser Ser Leu Asp Gly Asp Leu Ala Gly Arg Tyr Tyr Ala Leu
165 170 175
Lys Ser Met Thr Glu Ala Glu Gln Gln Gln Leu Ile Asp Asp His Phe
180 185 190
Leu Phe Asp Lys Pro Val Ser Pro Leu Leu Leu Ala Ser Gly Met Ala
195 200 205
Arg Asp Trp Pro Asp Ala Arg Gly Ile Trp His Asn Asp Asn Lys Thr
210 215 220
Phe Leu Val Trp Val Asn Glu Glu Asp His Leu Arg Val Ile Ser Met
225 230 235 240
Gln Lys Gly Gly Asn Met Lys Glu Val Phe Thr Arg Phe Cys Thr Gly
245 250 255
Leu Thr Gln Ile Glu Thr Leu Phe Lys Ser Lys Asp Tyr Glu Phe Met
260 265 270
Trp Asn Pro His Leu Gly Tyr Ile Leu Thr Cys Pro Ser Asn Leu Gly
275 280 285
Thr Gly Leu Arg Ala Gly Val His Ile Lys Leu Pro Asn Leu Gly Lys
290 295 300
His Glu Lys Phe Ser Glu Val Leu Lys Arg Leu Arg Leu Gln Lys Arg
305 310 315 320
Gly Thr Gly Gly Val Asp Thr Ala Ala Val Gly Gly Val Phe Asp Val
325 330 335
Ser Asn Ala Asp Arg Leu Gly Phe Ser Glu Val Glu Leu Val Gln Met
340 345 350
Val Val Asp Gly Val Lys Leu Leu Ile Glu Met Glu Gln Arg Leu Glu
355 360 365
Gln Gly Gln Ala Ile Asp Asp Leu Met Pro Ala Gln Lys
370 375 380
<210> 40
<211> 215
<212> PRT
<213> 智人
<400> 40
Met Gly Leu Glu Lys Pro Gln Ser Lys Leu Glu Gly Gly Met His Pro
1 5 10 15
Gln Leu Ile Pro Ser Val Ile Ala Val Val Phe Ile Leu Leu Leu Ser
20 25 30
Val Cys Phe Ile Ala Ser Cys Leu Val Thr His His Asn Phe Ser Arg
35 40 45
Cys Lys Arg Gly Thr Gly Val His Lys Leu Glu His His Ala Lys Leu
50 55 60
Lys Cys Ile Lys Glu Lys Ser Glu Leu Lys Ser Ala Glu Gly Ser Thr
65 70 75 80
Trp Asn Cys Cys Pro Ile Asp Trp Arg Ala Phe Gln Ser Asn Cys Tyr
85 90 95
Phe Pro Leu Thr Asp Asn Lys Thr Trp Ala Glu Ser Glu Arg Asn Cys
100 105 110
Ser Gly Met Gly Ala His Leu Met Thr Ile Ser Thr Glu Ala Glu Gln
115 120 125
Asn Phe Ile Ile Gln Phe Leu Asp Arg Arg Leu Ser Tyr Phe Leu Gly
130 135 140
Leu Arg Asp Glu Asn Ala Lys Gly Gln Trp Arg Trp Val Asp Gln Thr
145 150 155 160
Pro Phe Asn Pro Arg Arg Val Phe Trp His Lys Asn Glu Pro Asp Asn
165 170 175
Ser Gln Gly Glu Asn Cys Val Val Leu Val Tyr Asn Gln Asp Lys Trp
180 185 190
Ala Trp Asn Asp Val Pro Cys Asn Phe Glu Ala Ser Arg Ile Cys Lys
195 200 205
Ile Pro Gly Thr Thr Leu Asn
210 215
<210> 41
<211> 449
<212> PRT
<213> 智人
<400> 41
Met Met Lys Thr Leu Leu Leu Phe Val Gly Leu Leu Leu Thr Trp Glu
1 5 10 15
Ser Gly Gln Val Leu Gly Asp Gln Thr Val Ser Asp Asn Glu Leu Gln
20 25 30
Glu Met Ser Asn Gln Gly Ser Lys Tyr Val Asn Lys Glu Ile Gln Asn
35 40 45
Ala Val Asn Gly Val Lys Gln Ile Lys Thr Leu Ile Glu Lys Thr Asn
50 55 60
Glu Glu Arg Lys Thr Leu Leu Ser Asn Leu Glu Glu Ala Lys Lys Lys
65 70 75 80
Lys Glu Asp Ala Leu Asn Glu Thr Arg Glu Ser Glu Thr Lys Leu Lys
85 90 95
Glu Leu Pro Gly Val Cys Asn Glu Thr Met Met Ala Leu Trp Glu Glu
100 105 110
Cys Lys Pro Cys Leu Lys Gln Thr Cys Met Lys Phe Tyr Ala Arg Val
115 120 125
Cys Arg Ser Gly Ser Gly Leu Val Gly Arg Gln Leu Glu Glu Phe Leu
130 135 140
Asn Gln Ser Ser Pro Phe Tyr Phe Trp Met Asn Gly Asp Arg Ile Asp
145 150 155 160
Ser Leu Leu Glu Asn Asp Arg Gln Gln Thr His Met Leu Asp Val Met
165 170 175
Gln Asp His Phe Ser Arg Ala Ser Ser Ile Ile Asp Glu Leu Phe Gln
180 185 190
Asp Arg Phe Phe Thr Arg Glu Pro Gln Asp Thr Tyr His Tyr Leu Pro
195 200 205
Phe Ser Leu Pro His Arg Arg Pro His Phe Phe Phe Pro Lys Ser Arg
210 215 220
Ile Val Arg Ser Leu Met Pro Phe Ser Pro Tyr Glu Pro Leu Asn Phe
225 230 235 240
His Ala Met Phe Gln Pro Phe Leu Glu Met Ile His Glu Ala Gln Gln
245 250 255
Ala Met Asp Ile His Phe His Ser Pro Ala Phe Gln His Pro Pro Thr
260 265 270
Glu Phe Ile Arg Glu Gly Asp Asp Asp Arg Thr Val Cys Arg Glu Ile
275 280 285
Arg His Asn Ser Thr Gly Cys Leu Arg Met Lys Asp Gln Cys Asp Lys
290 295 300
Cys Arg Glu Ile Leu Ser Val Asp Cys Ser Thr Asn Asn Pro Ser Gln
305 310 315 320
Ala Lys Leu Arg Arg Glu Leu Asp Glu Ser Leu Gln Val Ala Glu Arg
325 330 335
Leu Thr Arg Lys Tyr Asn Glu Leu Leu Lys Ser Tyr Gln Trp Lys Met
340 345 350
Leu Asn Thr Ser Ser Leu Leu Glu Gln Leu Asn Glu Gln Phe Asn Trp
355 360 365
Val Ser Arg Leu Ala Asn Leu Thr Gln Gly Glu Asp Gln Tyr Tyr Leu
370 375 380
Arg Val Thr Thr Val Ala Ser His Thr Ser Asp Ser Asp Val Pro Ser
385 390 395 400
Gly Val Thr Glu Val Val Val Lys Leu Phe Asp Ser Asp Pro Ile Thr
405 410 415
Val Thr Val Pro Val Glu Val Ser Arg Lys Asn Pro Lys Phe Met Glu
420 425 430
Thr Val Ala Glu Lys Ala Leu Gln Glu Tyr Arg Lys Lys His Arg Glu
435 440 445
Glu
<210> 42
<211> 297
<212> PRT
<213> 智人
<400> 42
Met Ser Ser Ala His Phe Asn Arg Gly Pro Ala Tyr Gly Leu Ser Ala
1 5 10 15
Glu Val Lys Asn Lys Leu Ala Gln Lys Tyr Asp His Gln Arg Glu Gln
20 25 30
Glu Leu Arg Glu Trp Ile Glu Gly Val Thr Gly Arg Arg Ile Gly Asn
35 40 45
Asn Phe Met Asp Gly Leu Lys Asp Gly Ile Ile Leu Cys Glu Phe Ile
50 55 60
Asn Lys Leu Gln Pro Gly Ser Val Lys Lys Ile Asn Glu Ser Thr Gln
65 70 75 80
Asn Trp His Gln Leu Glu Asn Ile Gly Asn Phe Ile Lys Ala Ile Thr
85 90 95
Lys Tyr Gly Val Lys Pro His Asp Ile Phe Glu Ala Asn Asp Leu Phe
100 105 110
Glu Asn Thr Asn His Thr Gln Val Gln Ser Thr Leu Leu Ala Leu Ala
115 120 125
Ser Met Ala Lys Thr Lys Gly Asn Lys Val Asn Val Gly Val Lys Tyr
130 135 140
Ala Glu Lys Gln Glu Arg Lys Phe Glu Pro Gly Lys Leu Arg Glu Gly
145 150 155 160
Arg Asn Ile Ile Gly Leu Gln Met Gly Thr Asn Lys Phe Ala Ser Gln
165 170 175
Gln Gly Met Thr Ala Tyr Gly Thr Arg Arg His Leu Tyr Asp Pro Lys
180 185 190
Leu Gly Thr Asp Gln Pro Leu Asp Gln Ala Thr Ile Ser Leu Gln Met
195 200 205
Gly Thr Asn Lys Gly Ala Ser Gln Ala Gly Met Thr Ala Pro Gly Thr
210 215 220
Lys Arg Gln Ile Phe Glu Pro Gly Leu Gly Met Glu His Cys Asp Thr
225 230 235 240
Leu Asn Val Ser Leu Gln Met Gly Ser Asn Lys Gly Ala Ser Gln Arg
245 250 255
Gly Met Thr Val Tyr Gly Leu Pro Arg Gln Val Tyr Asp Pro Lys Tyr
260 265 270
Cys Leu Thr Pro Glu Tyr Pro Glu Leu Gly Glu Pro Ala His Asn His
275 280 285
His Ala His Asn Tyr Tyr Asn Ser Ala
290 295
<210> 43
<211> 474
<212> PRT
<213> 智人
<400> 43
Met Arg Arg Val Val Arg Gln Ser Lys Phe Arg His Val Phe Gly Gln
1 5 10 15
Ala Val Lys Asn Asp Gln Cys Tyr Asp Asp Ile Arg Val Ser Arg Val
20 25 30
Thr Trp Asp Ser Ser Phe Cys Ala Val Asn Pro Arg Phe Val Ala Ile
35 40 45
Ile Ile Glu Ala Ser Gly Gly Gly Ala Phe Leu Val Leu Pro Leu His
50 55 60
Lys Thr Gly Arg Ile Asp Lys Ser Tyr Pro Thr Val Cys Gly His Thr
65 70 75 80
Gly Pro Val Leu Asp Ile Asp Trp Cys Pro His Asn Asp Gln Val Ile
85 90 95
Ala Ser Gly Ser Glu Asp Cys Thr Val Met Val Trp Gln Ile Pro Glu
100 105 110
Asn Gly Leu Thr Leu Ser Leu Thr Glu Pro Val Val Ile Leu Glu Gly
115 120 125
His Ser Lys Arg Val Gly Ile Val Ala Trp His Pro Thr Ala Arg Asn
130 135 140
Val Leu Leu Ser Ala Gly Cys Asp Asn Ala Ile Ile Ile Trp Asn Val
145 150 155 160
Gly Thr Gly Glu Ala Leu Ile Asn Leu Asp Asp Met His Ser Asp Met
165 170 175
Ile Tyr Asn Val Ser Trp Asn Arg Asn Gly Ser Leu Ile Cys Thr Ala
180 185 190
Ser Lys Asp Lys Lys Val Arg Val Ile Asp Pro Arg Lys Gln Glu Ile
195 200 205
Val Ala Glu Lys Glu Lys Ala His Glu Gly Ala Arg Pro Met Arg Ala
210 215 220
Ile Phe Leu Ala Asp Gly Asn Val Phe Thr Thr Gly Phe Ser Arg Met
225 230 235 240
Ser Glu Arg Gln Leu Ala Leu Trp Asn Pro Lys Asn Met Gln Glu Pro
245 250 255
Ile Ala Leu His Glu Met Asp Thr Ser Asn Gly Val Leu Leu Pro Phe
260 265 270
Tyr Asp Pro Asp Thr Ser Ile Ile Tyr Leu Cys Gly Lys Gly Asp Ser
275 280 285
Ser Ile Arg Tyr Phe Glu Ile Thr Asp Glu Ser Pro Tyr Val His Tyr
290 295 300
Leu Asn Thr Phe Ser Ser Lys Glu Pro Gln Arg Gly Met Gly Tyr Met
305 310 315 320
Pro Lys Arg Gly Leu Asp Val Asn Lys Cys Glu Ile Ala Arg Phe Phe
325 330 335
Lys Leu His Glu Arg Lys Cys Glu Pro Ile Ile Met Thr Val Pro Arg
340 345 350
Lys Ser Asp Leu Phe Gln Asp Asp Leu Tyr Pro Asp Thr Ala Gly Pro
355 360 365
Glu Ala Ala Leu Glu Ala Glu Glu Trp Phe Glu Gly Lys Asn Ala Asp
370 375 380
Pro Ile Leu Ile Ser Leu Lys His Gly Tyr Ile Pro Gly Lys Asn Arg
385 390 395 400
Asp Leu Lys Val Val Lys Lys Asn Ile Leu Asp Ser Lys Pro Thr Ala
405 410 415
Asn Lys Lys Cys Asp Leu Ile Ser Ile Pro Lys Lys Thr Thr Asp Thr
420 425 430
Ala Ser Val Gln Asn Glu Ala Lys Leu Asp Glu Ile Leu Lys Glu Ile
435 440 445
Lys Ser Ile Lys Asp Thr Ile Cys Asn Gln Asp Glu Arg Ile Ser Lys
450 455 460
Leu Glu Gln Gln Met Ala Lys Ile Ala Ala
465 470
<210> 44
<211> 224
<212> PRT
<213> 智人
<400> 44
Met Glu Lys Leu Leu Cys Phe Leu Val Leu Thr Ser Leu Ser His Ala
1 5 10 15
Phe Gly Gln Thr Asp Met Ser Arg Lys Ala Phe Val Phe Pro Lys Glu
20 25 30
Ser Asp Thr Ser Tyr Val Ser Leu Lys Ala Pro Leu Thr Lys Pro Leu
35 40 45
Lys Ala Phe Thr Val Cys Leu His Phe Tyr Thr Glu Leu Ser Ser Thr
50 55 60
Arg Gly Tyr Ser Ile Phe Ser Tyr Ala Thr Lys Arg Gln Asp Asn Glu
65 70 75 80
Ile Leu Ile Phe Trp Ser Lys Asp Ile Gly Tyr Ser Phe Thr Val Gly
85 90 95
Gly Ser Glu Ile Leu Phe Glu Val Pro Glu Val Thr Val Ala Pro Val
100 105 110
His Ile Cys Thr Ser Trp Glu Ser Ala Ser Gly Ile Val Glu Phe Trp
115 120 125
Val Asp Gly Lys Pro Arg Val Arg Lys Ser Leu Lys Lys Gly Tyr Thr
130 135 140
Val Gly Ala Glu Ala Ser Ile Ile Leu Gly Gln Glu Gln Asp Ser Phe
145 150 155 160
Gly Gly Asn Phe Glu Gly Ser Gln Ser Leu Val Gly Asp Ile Gly Asn
165 170 175
Val Asn Met Trp Asp Phe Val Leu Ser Pro Asp Glu Ile Asn Thr Ile
180 185 190
Tyr Leu Gly Gly Pro Phe Ser Pro Asn Val Leu Asn Trp Arg Ala Leu
195 200 205
Lys Tyr Glu Val Gln Gly Glu Val Phe Thr Lys Pro Gln Leu Trp Pro
210 215 220
<210> 45
<211> 554
<212> PRT
<213> 智人
<400> 45
Met Thr Ala Pro Gly Ala Ala Gly Arg Cys Pro Pro Thr Thr Trp Leu
1 5 10 15
Gly Ser Leu Leu Leu Leu Val Cys Leu Leu Ala Ser Arg Ser Ile Thr
20 25 30
Glu Glu Val Ser Glu Tyr Cys Ser His Met Ile Gly Ser Gly His Leu
35 40 45
Gln Ser Leu Gln Arg Leu Ile Asp Ser Gln Met Glu Thr Ser Cys Gln
50 55 60
Ile Thr Phe Glu Phe Val Asp Gln Glu Gln Leu Lys Asp Pro Val Cys
65 70 75 80
Tyr Leu Lys Lys Ala Phe Leu Leu Val Gln Asp Ile Met Glu Asp Thr
85 90 95
Met Arg Phe Arg Asp Asn Thr Pro Asn Ala Ile Ala Ile Val Gln Leu
100 105 110
Gln Glu Leu Ser Leu Arg Leu Lys Ser Cys Phe Thr Lys Asp Tyr Glu
115 120 125
Glu His Asp Lys Ala Cys Val Arg Thr Phe Tyr Glu Thr Pro Leu Gln
130 135 140
Leu Leu Glu Lys Val Lys Asn Val Phe Asn Glu Thr Lys Asn Leu Leu
145 150 155 160
Asp Lys Asp Trp Asn Ile Phe Ser Lys Asn Cys Asn Asn Ser Phe Ala
165 170 175
Glu Cys Ser Ser Gln Asp Val Val Thr Lys Pro Asp Cys Asn Cys Leu
180 185 190
Tyr Pro Lys Ala Ile Pro Ser Ser Asp Pro Ala Ser Val Ser Pro His
195 200 205
Gln Pro Leu Ala Pro Ser Met Ala Pro Val Ala Gly Leu Thr Trp Glu
210 215 220
Asp Ser Glu Gly Thr Glu Gly Ser Ser Leu Leu Pro Gly Glu Gln Pro
225 230 235 240
Leu His Thr Val Asp Pro Gly Ser Ala Lys Gln Arg Pro Pro Arg Ser
245 250 255
Thr Cys Gln Ser Phe Glu Pro Pro Glu Thr Pro Val Val Lys Asp Ser
260 265 270
Thr Ile Gly Gly Ser Pro Gln Pro Arg Pro Ser Val Gly Ala Phe Asn
275 280 285
Pro Gly Met Glu Asp Ile Leu Asp Ser Ala Met Gly Thr Asn Trp Val
290 295 300
Pro Glu Glu Ala Ser Gly Glu Ala Ser Glu Ile Pro Val Pro Gln Gly
305 310 315 320
Thr Glu Leu Ser Pro Ser Arg Pro Gly Gly Gly Ser Met Gln Thr Glu
325 330 335
Pro Ala Arg Pro Ser Asn Phe Leu Ser Ala Ser Ser Pro Leu Pro Ala
340 345 350
Ser Ala Lys Gly Gln Gln Pro Ala Asp Val Thr Gly Thr Ala Leu Pro
355 360 365
Arg Val Gly Pro Val Arg Pro Thr Gly Gln Asp Trp Asn His Thr Pro
370 375 380
Gln Lys Thr Asp His Pro Ser Ala Leu Leu Arg Asp Pro Pro Glu Pro
385 390 395 400
Gly Ser Pro Arg Ile Ser Ser Leu Arg Pro Gln Gly Leu Ser Asn Pro
405 410 415
Ser Thr Leu Ser Ala Gln Pro Gln Leu Ser Arg Ser His Ser Ser Gly
420 425 430
Ser Val Leu Pro Leu Gly Glu Leu Glu Gly Arg Arg Ser Thr Arg Asp
435 440 445
Arg Arg Ser Pro Ala Glu Pro Glu Gly Gly Pro Ala Ser Glu Gly Ala
450 455 460
Ala Arg Pro Leu Pro Arg Phe Asn Ser Val Pro Leu Thr Asp Thr Gly
465 470 475 480
His Glu Arg Gln Ser Glu Gly Ser Phe Ser Pro Gln Leu Gln Glu Ser
485 490 495
Val Phe His Leu Leu Val Pro Ser Val Ile Leu Val Leu Leu Ala Val
500 505 510
Gly Gly Leu Leu Phe Tyr Arg Trp Arg Arg Arg Ser His Gln Glu Pro
515 520 525
Gln Arg Ala Asp Ser Pro Leu Glu Gln Pro Glu Gly Ser Pro Leu Thr
530 535 540
Gln Asp Asp Arg Gln Val Glu Leu Pro Val
545 550
<210> 46
<211> 781
<212> PRT
<213> 智人
<400> 46
Met Ala Thr Gln Ala Asp Leu Met Glu Leu Asp Met Ala Met Glu Pro
1 5 10 15
Asp Arg Lys Ala Ala Val Ser His Trp Gln Gln Gln Ser Tyr Leu Asp
20 25 30
Ser Gly Ile His Ser Gly Ala Thr Thr Thr Ala Pro Ser Leu Ser Gly
35 40 45
Lys Gly Asn Pro Glu Glu Glu Asp Val Asp Thr Ser Gln Val Leu Tyr
50 55 60
Glu Trp Glu Gln Gly Phe Ser Gln Ser Phe Thr Gln Glu Gln Val Ala
65 70 75 80
Asp Ile Asp Gly Gln Tyr Ala Met Thr Arg Ala Gln Arg Val Arg Ala
85 90 95
Ala Met Phe Pro Glu Thr Leu Asp Glu Gly Met Gln Ile Pro Ser Thr
100 105 110
Gln Phe Asp Ala Ala His Pro Thr Asn Val Gln Arg Leu Ala Glu Pro
115 120 125
Ser Gln Met Leu Lys His Ala Val Val Asn Leu Ile Asn Tyr Gln Asp
130 135 140
Asp Ala Glu Leu Ala Thr Arg Ala Ile Pro Glu Leu Thr Lys Leu Leu
145 150 155 160
Asn Asp Glu Asp Gln Val Val Val Asn Lys Ala Ala Val Met Val His
165 170 175
Gln Leu Ser Lys Lys Glu Ala Ser Arg His Ala Ile Met Arg Ser Pro
180 185 190
Gln Met Val Ser Ala Ile Val Arg Thr Met Gln Asn Thr Asn Asp Val
195 200 205
Glu Thr Ala Arg Cys Thr Ala Gly Thr Leu His Asn Leu Ser His His
210 215 220
Arg Glu Gly Leu Leu Ala Ile Phe Lys Ser Gly Gly Ile Pro Ala Leu
225 230 235 240
Val Lys Met Leu Gly Ser Pro Val Asp Ser Val Leu Phe Tyr Ala Ile
245 250 255
Thr Thr Leu His Asn Leu Leu Leu His Gln Glu Gly Ala Lys Met Ala
260 265 270
Val Arg Leu Ala Gly Gly Leu Gln Lys Met Val Ala Leu Leu Asn Lys
275 280 285
Thr Asn Val Lys Phe Leu Ala Ile Thr Thr Asp Cys Leu Gln Ile Leu
290 295 300
Ala Tyr Gly Asn Gln Glu Ser Lys Leu Ile Ile Leu Ala Ser Gly Gly
305 310 315 320
Pro Gln Ala Leu Val Asn Ile Met Arg Thr Tyr Thr Tyr Glu Lys Leu
325 330 335
Leu Trp Thr Thr Ser Arg Val Leu Lys Val Leu Ser Val Cys Ser Ser
340 345 350
Asn Lys Pro Ala Ile Val Glu Ala Gly Gly Met Gln Ala Leu Gly Leu
355 360 365
His Leu Thr Asp Pro Ser Gln Arg Leu Val Gln Asn Cys Leu Trp Thr
370 375 380
Leu Arg Asn Leu Ser Asp Ala Ala Thr Lys Gln Glu Gly Met Glu Gly
385 390 395 400
Leu Leu Gly Thr Leu Val Gln Leu Leu Gly Ser Asp Asp Ile Asn Val
405 410 415
Val Thr Cys Ala Ala Gly Ile Leu Ser Asn Leu Thr Cys Asn Asn Tyr
420 425 430
Lys Asn Lys Met Met Val Cys Gln Val Gly Gly Ile Glu Ala Leu Val
435 440 445
Arg Thr Val Leu Arg Ala Gly Asp Arg Glu Asp Ile Thr Glu Pro Ala
450 455 460
Ile Cys Ala Leu Arg His Leu Thr Ser Arg His Gln Glu Ala Glu Met
465 470 475 480
Ala Gln Asn Ala Val Arg Leu His Tyr Gly Leu Pro Val Val Val Lys
485 490 495
Leu Leu His Pro Pro Ser His Trp Pro Leu Ile Lys Ala Thr Val Gly
500 505 510
Leu Ile Arg Asn Leu Ala Leu Cys Pro Ala Asn His Ala Pro Leu Arg
515 520 525
Glu Gln Gly Ala Ile Pro Arg Leu Val Gln Leu Leu Val Arg Ala His
530 535 540
Gln Asp Thr Gln Arg Arg Thr Ser Met Gly Gly Thr Gln Gln Gln Phe
545 550 555 560
Val Glu Gly Val Arg Met Glu Glu Ile Val Glu Gly Cys Thr Gly Ala
565 570 575
Leu His Ile Leu Ala Arg Asp Val His Asn Arg Ile Val Ile Arg Gly
580 585 590
Leu Asn Thr Ile Pro Leu Phe Val Gln Leu Leu Tyr Ser Pro Ile Glu
595 600 605
Asn Ile Gln Arg Val Ala Ala Gly Val Leu Cys Glu Leu Ala Gln Asp
610 615 620
Lys Glu Ala Ala Glu Ala Ile Glu Ala Glu Gly Ala Thr Ala Pro Leu
625 630 635 640
Thr Glu Leu Leu His Ser Arg Asn Glu Gly Val Ala Thr Tyr Ala Ala
645 650 655
Ala Val Leu Phe Arg Met Ser Glu Asp Lys Pro Gln Asp Tyr Lys Lys
660 665 670
Arg Leu Ser Val Glu Leu Thr Ser Ser Leu Phe Arg Thr Glu Pro Met
675 680 685
Ala Trp Asn Glu Thr Ala Asp Leu Gly Leu Asp Ile Gly Ala Gln Gly
690 695 700
Glu Pro Leu Gly Tyr Arg Gln Asp Asp Pro Ser Tyr Arg Ser Phe His
705 710 715 720
Ser Gly Gly Tyr Gly Gln Asp Ala Leu Gly Met Asp Pro Met Met Glu
725 730 735
His Glu Met Gly Gly His His Pro Gly Ala Asp Tyr Pro Val Asp Gly
740 745 750
Leu Pro Asp Leu Gly His Ala Gln Asp Leu Met Asp Gly Leu Pro Pro
755 760 765
Gly Asp Ser Asn Gln Leu Ala Trp Phe Asp Thr Asp Leu
770 775 780
<210> 47
<211> 412
<212> PRT
<213> 智人
<400> 47
Met Gln Pro Ser Ser Leu Leu Pro Leu Ala Leu Cys Leu Leu Ala Ala
1 5 10 15
Pro Ala Ser Ala Leu Val Arg Ile Pro Leu His Lys Phe Thr Ser Ile
20 25 30
Arg Arg Thr Met Ser Glu Val Gly Gly Ser Val Glu Asp Leu Ile Ala
35 40 45
Lys Gly Pro Val Ser Lys Tyr Ser Gln Ala Val Pro Ala Val Thr Glu
50 55 60
Gly Pro Ile Pro Glu Val Leu Lys Asn Tyr Met Asp Ala Gln Tyr Tyr
65 70 75 80
Gly Glu Ile Gly Ile Gly Thr Pro Pro Gln Cys Phe Thr Val Val Phe
85 90 95
Asp Thr Gly Ser Ser Asn Leu Trp Val Pro Ser Ile His Cys Lys Leu
100 105 110
Leu Asp Ile Ala Cys Trp Ile His His Lys Tyr Asn Ser Asp Lys Ser
115 120 125
Ser Thr Tyr Val Lys Asn Gly Thr Ser Phe Asp Ile His Tyr Gly Ser
130 135 140
Gly Ser Leu Ser Gly Tyr Leu Ser Gln Asp Thr Val Ser Val Pro Cys
145 150 155 160
Gln Ser Ala Ser Ser Ala Ser Ala Leu Gly Gly Val Lys Val Glu Arg
165 170 175
Gln Val Phe Gly Glu Ala Thr Lys Gln Pro Gly Ile Thr Phe Ile Ala
180 185 190
Ala Lys Phe Asp Gly Ile Leu Gly Met Ala Tyr Pro Arg Ile Ser Val
195 200 205
Asn Asn Val Leu Pro Val Phe Asp Asn Leu Met Gln Gln Lys Leu Val
210 215 220
Asp Gln Asn Ile Phe Ser Phe Tyr Leu Ser Arg Asp Pro Asp Ala Gln
225 230 235 240
Pro Gly Gly Glu Leu Met Leu Gly Gly Thr Asp Ser Lys Tyr Tyr Lys
245 250 255
Gly Ser Leu Ser Tyr Leu Asn Val Thr Arg Lys Ala Tyr Trp Gln Val
260 265 270
His Leu Asp Gln Val Glu Val Ala Ser Gly Leu Thr Leu Cys Lys Glu
275 280 285
Gly Cys Glu Ala Ile Val Asp Thr Gly Thr Ser Leu Met Val Gly Pro
290 295 300
Val Asp Glu Val Arg Glu Leu Gln Lys Ala Ile Gly Ala Val Pro Leu
305 310 315 320
Ile Gln Gly Glu Tyr Met Ile Pro Cys Glu Lys Val Ser Thr Leu Pro
325 330 335
Ala Ile Thr Leu Lys Leu Gly Gly Lys Gly Tyr Lys Leu Ser Pro Glu
340 345 350
Asp Tyr Thr Leu Lys Val Ser Gln Ala Gly Lys Thr Leu Cys Leu Ser
355 360 365
Gly Phe Met Gly Met Asp Ile Pro Pro Pro Ser Gly Pro Leu Trp Ile
370 375 380
Leu Gly Asp Val Phe Ile Gly Arg Tyr Tyr Thr Val Phe Asp Arg Asp
385 390 395 400
Asn Asn Arg Val Gly Phe Ala Glu Ala Ala Arg Leu
405 410
<210> 48
<211> 331
<212> PRT
<213> 智人
<400> 48
Met Lys Arg Leu Val Cys Val Leu Leu Val Cys Ser Ser Ala Val Ala
1 5 10 15
Gln Leu His Lys Asp Pro Thr Leu Asp His His Trp His Leu Trp Lys
20 25 30
Lys Thr Tyr Gly Lys Gln Tyr Lys Glu Lys Asn Glu Glu Ala Val Arg
35 40 45
Arg Leu Ile Trp Glu Lys Asn Leu Lys Phe Val Met Leu His Asn Leu
50 55 60
Glu His Ser Met Gly Met His Ser Tyr Asp Leu Gly Met Asn His Leu
65 70 75 80
Gly Asp Met Thr Ser Glu Glu Val Met Ser Leu Met Ser Ser Leu Arg
85 90 95
Val Pro Ser Gln Trp Gln Arg Asn Ile Thr Tyr Lys Ser Asn Pro Asn
100 105 110
Arg Ile Leu Pro Asp Ser Val Asp Trp Arg Glu Lys Gly Cys Val Thr
115 120 125
Glu Val Lys Tyr Gln Gly Ser Cys Gly Ala Cys Trp Ala Phe Ser Ala
130 135 140
Val Gly Ala Leu Glu Ala Gln Leu Lys Leu Lys Thr Gly Lys Leu Val
145 150 155 160
Ser Leu Ser Ala Gln Asn Leu Val Asp Cys Ser Thr Glu Lys Tyr Gly
165 170 175
Asn Lys Gly Cys Asn Gly Gly Phe Met Thr Thr Ala Phe Gln Tyr Ile
180 185 190
Ile Asp Asn Lys Gly Ile Asp Ser Asp Ala Ser Tyr Pro Tyr Lys Ala
195 200 205
Met Asp Gln Lys Cys Gln Tyr Asp Ser Lys Tyr Arg Ala Ala Thr Cys
210 215 220
Ser Lys Tyr Thr Glu Leu Pro Tyr Gly Arg Glu Asp Val Leu Lys Glu
225 230 235 240
Ala Val Ala Asn Lys Gly Pro Val Ser Val Gly Val Asp Ala Arg His
245 250 255
Pro Ser Phe Phe Leu Tyr Arg Ser Gly Val Tyr Tyr Glu Pro Ser Cys
260 265 270
Thr Gln Asn Val Asn His Gly Val Leu Val Val Gly Tyr Gly Asp Leu
275 280 285
Asn Gly Lys Glu Tyr Trp Leu Val Lys Asn Ser Trp Gly His Asn Phe
290 295 300
Gly Glu Glu Gly Tyr Ile Arg Met Ala Arg Asn Lys Gly Asn His Cys
305 310 315 320
Gly Ile Ala Ser Phe Pro Ser Tyr Pro Glu Ile
325 330
<210> 49
<211> 303
<212> PRT
<213> 智人
<400> 49
Met Ala Arg Arg Gly Pro Gly Trp Arg Pro Leu Leu Leu Leu Val Leu
1 5 10 15
Leu Ala Gly Ala Ala Gln Gly Gly Leu Tyr Phe Arg Arg Gly Gln Thr
20 25 30
Cys Tyr Arg Pro Leu Arg Gly Asp Gly Leu Ala Pro Leu Gly Arg Ser
35 40 45
Thr Tyr Pro Arg Pro His Glu Tyr Leu Ser Pro Ala Asp Leu Pro Lys
50 55 60
Ser Trp Asp Trp Arg Asn Val Asp Gly Val Asn Tyr Ala Ser Ile Thr
65 70 75 80
Arg Asn Gln His Ile Pro Gln Tyr Cys Gly Ser Cys Trp Ala His Ala
85 90 95
Ser Thr Ser Ala Met Ala Asp Arg Ile Asn Ile Lys Arg Lys Gly Ala
100 105 110
Trp Pro Ser Thr Leu Leu Ser Val Gln Asn Val Ile Asp Cys Gly Asn
115 120 125
Ala Gly Ser Cys Glu Gly Gly Asn Asp Leu Ser Val Trp Asp Tyr Ala
130 135 140
His Gln His Gly Ile Pro Asp Glu Thr Cys Asn Asn Tyr Gln Ala Lys
145 150 155 160
Asp Gln Glu Cys Asp Lys Phe Asn Gln Cys Gly Thr Cys Asn Glu Phe
165 170 175
Lys Glu Cys His Ala Ile Arg Asn Tyr Thr Leu Trp Arg Val Gly Asp
180 185 190
Tyr Gly Ser Leu Ser Gly Arg Glu Lys Met Met Ala Glu Ile Tyr Ala
195 200 205
Asn Gly Pro Ile Ser Cys Gly Ile Met Ala Thr Glu Arg Leu Ala Asn
210 215 220
Tyr Thr Gly Gly Ile Tyr Ala Glu Tyr Gln Asp Thr Thr Tyr Ile Asn
225 230 235 240
His Val Val Ser Val Ala Gly Trp Gly Ile Ser Asp Gly Thr Glu Tyr
245 250 255
Trp Ile Val Arg Asn Ser Trp Gly Glu Pro Trp Gly Glu Arg Gly Trp
260 265 270
Leu Arg Ile Val Thr Ser Thr Tyr Lys Asp Gly Lys Gly Ala Arg Tyr
275 280 285
Asn Leu Ala Ile Glu Glu His Cys Thr Phe Gly Asp Pro Ile Val
290 295 300
<210> 50
<211> 776
<212> PRT
<213> 智人
<400> 50
Met Ser Ser Thr Arg Ser Gln Asn Pro His Gly Leu Lys Gln Ile Gly
1 5 10 15
Leu Asp Gln Ile Trp Asp Asp Leu Arg Ala Gly Ile Gln Gln Val Tyr
20 25 30
Thr Arg Gln Ser Met Ala Lys Ser Arg Tyr Met Glu Leu Tyr Thr His
35 40 45
Val Tyr Asn Tyr Cys Thr Ser Val His Gln Ser Asn Gln Ala Arg Gly
50 55 60
Ala Gly Val Pro Pro Ser Lys Ser Lys Lys Gly Gln Thr Pro Gly Gly
65 70 75 80
Ala Gln Phe Val Gly Leu Glu Leu Tyr Lys Arg Leu Lys Glu Phe Leu
85 90 95
Lys Asn Tyr Leu Thr Asn Leu Leu Lys Asp Gly Glu Asp Leu Met Asp
100 105 110
Glu Ser Val Leu Lys Phe Tyr Thr Gln Gln Trp Glu Asp Tyr Arg Phe
115 120 125
Ser Ser Lys Val Leu Asn Gly Ile Cys Ala Tyr Leu Asn Arg His Trp
130 135 140
Val Arg Arg Glu Cys Asp Glu Gly Arg Lys Gly Ile Tyr Glu Ile Tyr
145 150 155 160
Ser Leu Ala Leu Val Thr Trp Arg Asp Cys Leu Phe Arg Pro Leu Asn
165 170 175
Lys Gln Val Thr Asn Ala Val Leu Lys Leu Ile Glu Lys Glu Arg Asn
180 185 190
Gly Glu Thr Ile Asn Thr Arg Leu Ile Ser Gly Val Val Gln Ser Tyr
195 200 205
Val Glu Leu Gly Leu Asn Glu Asp Asp Ala Phe Ala Lys Gly Pro Thr
210 215 220
Leu Thr Val Tyr Lys Glu Ser Phe Glu Ser Gln Phe Leu Ala Asp Thr
225 230 235 240
Glu Arg Phe Tyr Thr Arg Glu Ser Thr Glu Phe Leu Gln Gln Asn Pro
245 250 255
Val Thr Glu Tyr Met Lys Lys Ala Glu Ala Arg Leu Leu Glu Glu Gln
260 265 270
Arg Arg Val Gln Val Tyr Leu His Glu Ser Thr Gln Asp Glu Leu Ala
275 280 285
Arg Lys Cys Glu Gln Val Leu Ile Glu Lys His Leu Glu Ile Phe His
290 295 300
Thr Glu Phe Gln Asn Leu Leu Asp Ala Asp Lys Asn Glu Asp Leu Gly
305 310 315 320
Arg Met Tyr Asn Leu Val Ser Arg Ile Gln Asp Gly Leu Gly Glu Leu
325 330 335
Lys Lys Leu Leu Glu Thr His Ile His Asn Gln Gly Leu Ala Ala Ile
340 345 350
Glu Lys Cys Gly Glu Ala Ala Leu Asn Asp Pro Lys Met Tyr Val Gln
355 360 365
Thr Val Leu Asp Val His Lys Lys Tyr Asn Ala Leu Val Met Ser Ala
370 375 380
Phe Asn Asn Asp Ala Gly Phe Val Ala Ala Leu Asp Lys Ala Cys Gly
385 390 395 400
Arg Phe Ile Asn Asn Asn Ala Val Thr Lys Met Ala Gln Ser Ser Ser
405 410 415
Lys Ser Pro Glu Leu Leu Ala Arg Tyr Cys Asp Ser Leu Leu Lys Lys
420 425 430
Ser Ser Lys Asn Pro Glu Glu Ala Glu Leu Glu Asp Thr Leu Asn Gln
435 440 445
Val Met Val Val Phe Lys Tyr Ile Glu Asp Lys Asp Val Phe Gln Lys
450 455 460
Phe Tyr Ala Lys Met Leu Ala Lys Arg Leu Val His Gln Asn Ser Ala
465 470 475 480
Ser Asp Asp Ala Glu Ala Ser Met Ile Ser Lys Leu Lys Gln Ala Cys
485 490 495
Gly Phe Glu Tyr Thr Ser Lys Leu Gln Arg Met Phe Gln Asp Ile Gly
500 505 510
Val Ser Lys Asp Leu Asn Glu Gln Phe Lys Lys His Leu Thr Asn Ser
515 520 525
Glu Pro Leu Asp Leu Asp Phe Ser Ile Gln Val Leu Ser Ser Gly Ser
530 535 540
Trp Pro Phe Gln Gln Ser Cys Thr Phe Ala Leu Pro Ser Glu Leu Glu
545 550 555 560
Arg Ser Tyr Gln Arg Phe Thr Ala Phe Tyr Ala Ser Arg His Ser Gly
565 570 575
Arg Lys Leu Thr Trp Leu Tyr Gln Leu Ser Lys Gly Glu Leu Val Thr
580 585 590
Asn Cys Phe Lys Asn Arg Tyr Thr Leu Gln Ala Ser Thr Phe Gln Met
595 600 605
Ala Ile Leu Leu Gln Tyr Asn Thr Glu Asp Ala Tyr Thr Val Gln Gln
610 615 620
Leu Thr Asp Ser Thr Gln Ile Lys Met Asp Ile Leu Ala Gln Val Leu
625 630 635 640
Gln Ile Leu Leu Lys Ser Lys Leu Leu Val Leu Glu Asp Glu Asn Ala
645 650 655
Asn Val Asp Glu Val Glu Leu Lys Pro Asp Thr Leu Ile Lys Leu Tyr
660 665 670
Leu Gly Tyr Lys Asn Lys Lys Leu Arg Val Asn Ile Asn Val Pro Met
675 680 685
Lys Thr Glu Gln Lys Gln Glu Gln Glu Thr Thr His Lys Asn Ile Glu
690 695 700
Glu Asp Arg Lys Leu Leu Ile Gln Ala Ala Ile Val Arg Ile Met Lys
705 710 715 720
Met Arg Lys Val Leu Lys His Gln Gln Leu Leu Gly Glu Val Leu Thr
725 730 735
Gln Leu Ser Ser Arg Phe Lys Pro Arg Val Pro Val Ile Lys Lys Cys
740 745 750
Ile Asp Ile Leu Ile Glu Lys Glu Tyr Leu Glu Arg Val Asp Gly Glu
755 760 765
Lys Asp Thr Tyr Ser Tyr Leu Ala
770 775
<210> 51
<211> 501
<212> PRT
<213> 智人
<400> 51
Met Pro Ser Ala Ser Ala Ser Arg Lys Ser Gln Glu Lys Pro Arg Glu
1 5 10 15
Ile Met Asp Ala Ala Glu Asp Tyr Ala Lys Glu Arg Tyr Gly Ile Ser
20 25 30
Ser Met Ile Gln Ser Gln Glu Lys Pro Asp Arg Val Leu Val Arg Val
35 40 45
Arg Asp Leu Thr Ile Gln Lys Ala Asp Glu Val Val Trp Val Arg Ala
50 55 60
Arg Val His Thr Ser Arg Ala Lys Gly Lys Gln Cys Phe Leu Val Leu
65 70 75 80
Arg Gln Gln Gln Phe Asn Val Gln Ala Leu Val Ala Val Gly Asp His
85 90 95
Ala Ser Lys Gln Met Val Lys Phe Ala Ala Asn Ile Asn Lys Glu Ser
100 105 110
Ile Val Asp Val Glu Gly Val Val Arg Lys Val Asn Gln Lys Ile Gly
115 120 125
Ser Cys Thr Gln Gln Asp Val Glu Leu His Val Gln Lys Ile Tyr Val
130 135 140
Ile Ser Leu Ala Glu Pro Arg Leu Pro Leu Gln Leu Asp Asp Ala Val
145 150 155 160
Arg Pro Glu Ala Glu Gly Glu Glu Glu Gly Arg Ala Thr Val Asn Gln
165 170 175
Asp Thr Arg Leu Asp Asn Arg Val Ile Asp Leu Arg Thr Ser Thr Ser
180 185 190
Gln Ala Val Phe Arg Leu Gln Ser Gly Ile Cys His Leu Phe Arg Glu
195 200 205
Thr Leu Ile Asn Lys Gly Phe Val Glu Ile Gln Thr Pro Lys Ile Ile
210 215 220
Ser Ala Ala Ser Glu Gly Gly Ala Asn Val Phe Thr Val Ser Tyr Phe
225 230 235 240
Lys Asn Asn Ala Tyr Leu Ala Gln Ser Pro Gln Leu Tyr Lys Gln Met
245 250 255
Cys Ile Cys Ala Asp Phe Glu Lys Val Phe Ser Ile Gly Pro Val Phe
260 265 270
Arg Ala Glu Asp Ser Asn Thr His Arg His Leu Thr Glu Phe Val Gly
275 280 285
Leu Asp Ile Glu Met Ala Phe Asn Tyr His Tyr His Glu Val Met Glu
290 295 300
Glu Ile Ala Asp Thr Met Val Gln Ile Phe Lys Gly Leu Gln Glu Arg
305 310 315 320
Phe Gln Thr Glu Ile Gln Thr Val Asn Lys Gln Phe Pro Cys Glu Pro
325 330 335
Phe Lys Phe Leu Glu Pro Thr Leu Arg Leu Glu Tyr Cys Glu Ala Leu
340 345 350
Ala Met Leu Arg Glu Ala Gly Val Glu Met Gly Asp Glu Asp Asp Leu
355 360 365
Ser Thr Pro Asn Glu Lys Leu Leu Gly His Leu Val Lys Glu Lys Tyr
370 375 380
Asp Thr Asp Phe Tyr Ile Leu Asp Lys Tyr Pro Leu Ala Val Arg Pro
385 390 395 400
Phe Tyr Thr Met Pro Asp Pro Arg Asn Pro Lys Gln Ser Asn Ser Tyr
405 410 415
Asp Met Phe Met Arg Gly Glu Glu Ile Leu Ser Gly Ala Gln Arg Ile
420 425 430
His Asp Pro Gln Leu Leu Thr Glu Arg Ala Leu His His Gly Ile Asp
435 440 445
Leu Glu Lys Ile Lys Ala Tyr Ile Asp Ser Phe Arg Phe Gly Ala Pro
450 455 460
Pro His Ala Gly Gly Gly Ile Gly Leu Glu Arg Val Thr Met Leu Phe
465 470 475 480
Leu Gly Leu His Asn Val Arg Gln Thr Ser Met Phe Pro Arg Asp Pro
485 490 495
Lys Arg Leu Thr Pro
500
<210> 52
<211> 94
<212> PRT
<213> 智人
<400> 52
Met Arg Thr Leu Ala Ile Leu Ala Ala Ile Leu Leu Val Ala Leu Gln
1 5 10 15
Ala Gln Ala Glu Pro Leu Gln Ala Arg Ala Asp Glu Val Ala Ala Ala
20 25 30
Pro Glu Gln Ile Ala Ala Asp Ile Pro Glu Val Val Val Ser Leu Ala
35 40 45
Trp Asp Glu Ser Leu Ala Pro Lys His Pro Gly Ser Arg Lys Asn Met
50 55 60
Ala Cys Tyr Cys Arg Ile Pro Ala Cys Ile Ala Gly Glu Arg Arg Tyr
65 70 75 80
Gly Thr Cys Ile Tyr Gln Gly Arg Leu Trp Ala Phe Cys Cys
85 90
<210> 53
<211> 94
<212> PRT
<213> 智人
<400> 53
Met Arg Thr Leu Ala Ile Leu Ala Ala Ile Leu Leu Val Ala Leu Gln
1 5 10 15
Ala Gln Ala Glu Pro Leu Gln Ala Arg Ala Asp Glu Val Ala Ala Ala
20 25 30
Pro Glu Gln Ile Ala Ala Asp Ile Pro Glu Val Val Val Ser Leu Ala
35 40 45
Trp Asp Glu Ser Leu Ala Pro Lys His Pro Gly Ser Arg Lys Asn Met
50 55 60
Asp Cys Tyr Cys Arg Ile Pro Ala Cys Ile Ala Gly Glu Arg Arg Tyr
65 70 75 80
Gly Thr Cys Ile Tyr Gln Gly Arg Leu Trp Ala Phe Cys Cys
85 90
<210> 54
<211> 470
<212> PRT
<213> 智人
<400> 54
Met Ser Gln Ala Tyr Ser Ser Ser Gln Arg Val Ser Ser Tyr Arg Arg
1 5 10 15
Thr Phe Gly Gly Ala Pro Gly Phe Pro Leu Gly Ser Pro Leu Ser Ser
20 25 30
Pro Val Phe Pro Arg Ala Gly Phe Gly Ser Lys Gly Ser Ser Ser Ser
35 40 45
Val Thr Ser Arg Val Tyr Gln Val Ser Arg Thr Ser Gly Gly Ala Gly
50 55 60
Gly Leu Gly Ser Leu Arg Ala Ser Arg Leu Gly Thr Thr Arg Thr Pro
65 70 75 80
Ser Ser Tyr Gly Ala Gly Glu Leu Leu Asp Phe Ser Leu Ala Asp Ala
85 90 95
Val Asn Gln Glu Phe Leu Thr Thr Arg Thr Asn Glu Lys Val Glu Leu
100 105 110
Gln Glu Leu Asn Asp Arg Phe Ala Asn Tyr Ile Glu Lys Val Arg Phe
115 120 125
Leu Glu Gln Gln Asn Ala Ala Leu Ala Ala Glu Val Asn Arg Leu Lys
130 135 140
Gly Arg Glu Pro Thr Arg Val Ala Glu Leu Tyr Glu Glu Glu Leu Arg
145 150 155 160
Glu Leu Arg Arg Gln Val Glu Val Leu Thr Asn Gln Arg Ala Arg Val
165 170 175
Asp Val Glu Arg Asp Asn Leu Leu Asp Asp Leu Gln Arg Leu Lys Ala
180 185 190
Lys Leu Gln Glu Glu Ile Gln Leu Lys Glu Glu Ala Glu Asn Asn Leu
195 200 205
Ala Ala Phe Arg Ala Asp Val Asp Ala Ala Thr Leu Ala Arg Ile Asp
210 215 220
Leu Glu Arg Arg Ile Glu Ser Leu Asn Glu Glu Ile Ala Phe Leu Lys
225 230 235 240
Lys Val His Glu Glu Glu Ile Arg Glu Leu Gln Ala Gln Leu Gln Glu
245 250 255
Gln Gln Val Gln Val Glu Met Asp Met Ser Lys Pro Asp Leu Thr Ala
260 265 270
Ala Leu Arg Asp Ile Arg Ala Gln Tyr Glu Thr Ile Ala Ala Lys Asn
275 280 285
Ile Ser Glu Ala Glu Glu Trp Tyr Lys Ser Lys Val Ser Asp Leu Thr
290 295 300
Gln Ala Ala Asn Lys Asn Asn Asp Ala Leu Arg Gln Ala Lys Gln Glu
305 310 315 320
Met Met Glu Tyr Arg His Gln Ile Gln Ser Tyr Thr Cys Glu Ile Asp
325 330 335
Ala Leu Lys Gly Thr Asn Asp Ser Leu Met Arg Gln Met Arg Glu Leu
340 345 350
Glu Asp Arg Phe Ala Ser Glu Ala Ser Gly Tyr Gln Asp Asn Ile Ala
355 360 365
Arg Leu Glu Glu Glu Ile Arg His Leu Lys Asp Glu Met Ala Arg His
370 375 380
Leu Arg Glu Tyr Gln Asp Leu Leu Asn Val Lys Met Ala Leu Asp Val
385 390 395 400
Glu Ile Ala Thr Tyr Arg Lys Leu Leu Glu Gly Glu Glu Ser Arg Ile
405 410 415
Asn Leu Pro Ile Gln Thr Tyr Ser Ala Leu Asn Phe Arg Glu Thr Ser
420 425 430
Pro Glu Gln Arg Gly Ser Glu Val His Thr Lys Lys Thr Val Met Ile
435 440 445
Lys Thr Ile Glu Thr Arg Asp Gly Glu Val Val Ser Glu Ala Thr Gln
450 455 460
Gln Gln His Glu Val Leu
465 470
<210> 55
<211> 766
<212> PRT
<213> 智人
<400> 55
Met Lys Thr Pro Trp Lys Val Leu Leu Gly Leu Leu Gly Ala Ala Ala
1 5 10 15
Leu Val Thr Ile Ile Thr Val Pro Val Val Leu Leu Asn Lys Gly Thr
20 25 30
Asp Asp Ala Thr Ala Asp Ser Arg Lys Thr Tyr Thr Leu Thr Asp Tyr
35 40 45
Leu Lys Asn Thr Tyr Arg Leu Lys Leu Tyr Ser Leu Arg Trp Ile Ser
50 55 60
Asp His Glu Tyr Leu Tyr Lys Gln Glu Asn Asn Ile Leu Val Phe Asn
65 70 75 80
Ala Glu Tyr Gly Asn Ser Ser Val Phe Leu Glu Asn Ser Thr Phe Asp
85 90 95
Glu Phe Gly His Ser Ile Asn Asp Tyr Ser Ile Ser Pro Asp Gly Gln
100 105 110
Phe Ile Leu Leu Glu Tyr Asn Tyr Val Lys Gln Trp Arg His Ser Tyr
115 120 125
Thr Ala Ser Tyr Asp Ile Tyr Asp Leu Asn Lys Arg Gln Leu Ile Thr
130 135 140
Glu Glu Arg Ile Pro Asn Asn Thr Gln Trp Val Thr Trp Ser Pro Val
145 150 155 160
Gly His Lys Leu Ala Tyr Val Trp Asn Asn Asp Ile Tyr Val Lys Ile
165 170 175
Glu Pro Asn Leu Pro Ser Tyr Arg Ile Thr Trp Thr Gly Lys Glu Asp
180 185 190
Ile Ile Tyr Asn Gly Ile Thr Asp Trp Val Tyr Glu Glu Glu Val Phe
195 200 205
Ser Ala Tyr Ser Ala Leu Trp Trp Ser Pro Asn Gly Thr Phe Leu Ala
210 215 220
Tyr Ala Gln Phe Asn Asp Thr Glu Val Pro Leu Ile Glu Tyr Ser Phe
225 230 235 240
Tyr Ser Asp Glu Ser Leu Gln Tyr Pro Lys Thr Val Arg Val Pro Tyr
245 250 255
Pro Lys Ala Gly Ala Val Asn Pro Thr Val Lys Phe Phe Val Val Asn
260 265 270
Thr Asp Ser Leu Ser Ser Val Thr Asn Ala Thr Ser Ile Gln Ile Thr
275 280 285
Ala Pro Ala Ser Met Leu Ile Gly Asp His Tyr Leu Cys Asp Val Thr
290 295 300
Trp Ala Thr Gln Glu Arg Ile Ser Leu Gln Trp Leu Arg Arg Ile Gln
305 310 315 320
Asn Tyr Ser Val Met Asp Ile Cys Asp Tyr Asp Glu Ser Ser Gly Arg
325 330 335
Trp Asn Cys Leu Val Ala Arg Gln His Ile Glu Met Ser Thr Thr Gly
340 345 350
Trp Val Gly Arg Phe Arg Pro Ser Glu Pro His Phe Thr Leu Asp Gly
355 360 365
Asn Ser Phe Tyr Lys Ile Ile Ser Asn Glu Glu Gly Tyr Arg His Ile
370 375 380
Cys Tyr Phe Gln Ile Asp Lys Lys Asp Cys Thr Phe Ile Thr Lys Gly
385 390 395 400
Thr Trp Glu Val Ile Gly Ile Glu Ala Leu Thr Ser Asp Tyr Leu Tyr
405 410 415
Tyr Ile Ser Asn Glu Tyr Lys Gly Met Pro Gly Gly Arg Asn Leu Tyr
420 425 430
Lys Ile Gln Leu Ser Asp Tyr Thr Lys Val Thr Cys Leu Ser Cys Glu
435 440 445
Leu Asn Pro Glu Arg Cys Gln Tyr Tyr Ser Val Ser Phe Ser Lys Glu
450 455 460
Ala Lys Tyr Tyr Gln Leu Arg Cys Ser Gly Pro Gly Leu Pro Leu Tyr
465 470 475 480
Thr Leu His Ser Ser Val Asn Asp Lys Gly Leu Arg Val Leu Glu Asp
485 490 495
Asn Ser Ala Leu Asp Lys Met Leu Gln Asn Val Gln Met Pro Ser Lys
500 505 510
Lys Leu Asp Phe Ile Ile Leu Asn Glu Thr Lys Phe Trp Tyr Gln Met
515 520 525
Ile Leu Pro Pro His Phe Asp Lys Ser Lys Lys Tyr Pro Leu Leu Leu
530 535 540
Asp Val Tyr Ala Gly Pro Cys Ser Gln Lys Ala Asp Thr Val Phe Arg
545 550 555 560
Leu Asn Trp Ala Thr Tyr Leu Ala Ser Thr Glu Asn Ile Ile Val Ala
565 570 575
Ser Phe Asp Gly Arg Gly Ser Gly Tyr Gln Gly Asp Lys Ile Met His
580 585 590
Ala Ile Asn Arg Arg Leu Gly Thr Phe Glu Val Glu Asp Gln Ile Glu
595 600 605
Ala Ala Arg Gln Phe Ser Lys Met Gly Phe Val Asp Asn Lys Arg Ile
610 615 620
Ala Ile Trp Gly Trp Ser Tyr Gly Gly Tyr Val Thr Ser Met Val Leu
625 630 635 640
Gly Ser Gly Ser Gly Val Phe Lys Cys Gly Ile Ala Val Ala Pro Val
645 650 655
Ser Arg Trp Glu Tyr Tyr Asp Ser Val Tyr Thr Glu Arg Tyr Met Gly
660 665 670
Leu Pro Thr Pro Glu Asp Asn Leu Asp His Tyr Arg Asn Ser Thr Val
675 680 685
Met Ser Arg Ala Glu Asn Phe Lys Gln Val Glu Tyr Leu Leu Ile His
690 695 700
Gly Thr Ala Asp Asp Asn Val His Phe Gln Gln Ser Ala Gln Ile Ser
705 710 715 720
Lys Ala Leu Val Asp Val Gly Val Asp Phe Gln Ala Met Trp Tyr Thr
725 730 735
Asp Glu Asp His Gly Ile Ala Ser Ser Thr Ala His Gln His Ile Tyr
740 745 750
Thr His Met Ser His Phe Ile Lys Gln Cys Phe Ser Leu Pro
755 760 765
<210> 56
<211> 572
<212> PRT
<213> 智人
<400> 56
Met Ser Tyr Gln Gly Lys Lys Asn Ile Pro Arg Ile Thr Ser Asp Arg
1 5 10 15
Leu Leu Ile Lys Gly Gly Lys Ile Val Asn Asp Asp Gln Ser Phe Tyr
20 25 30
Ala Asp Ile Tyr Met Glu Asp Gly Leu Ile Lys Gln Ile Gly Glu Asn
35 40 45
Leu Ile Val Pro Gly Gly Val Lys Thr Ile Glu Ala His Ser Arg Met
50 55 60
Val Ile Pro Gly Gly Ile Asp Val His Thr Arg Phe Gln Met Pro Asp
65 70 75 80
Gln Gly Met Thr Ser Ala Asp Asp Phe Phe Gln Gly Thr Lys Ala Ala
85 90 95
Leu Ala Gly Gly Thr Thr Met Ile Ile Asp His Val Val Pro Glu Pro
100 105 110
Gly Thr Ser Leu Leu Ala Ala Phe Asp Gln Trp Arg Glu Trp Ala Asp
115 120 125
Ser Lys Ser Cys Cys Asp Tyr Ser Leu His Val Asp Ile Ser Glu Trp
130 135 140
His Lys Gly Ile Gln Glu Glu Met Glu Ala Leu Val Lys Asp His Gly
145 150 155 160
Val Asn Ser Phe Leu Val Tyr Met Ala Phe Lys Asp Arg Phe Gln Leu
165 170 175
Thr Asp Cys Gln Ile Tyr Glu Val Leu Ser Val Ile Arg Asp Ile Gly
180 185 190
Ala Ile Ala Gln Val His Ala Glu Asn Gly Asp Ile Ile Ala Glu Glu
195 200 205
Gln Gln Arg Ile Leu Asp Leu Gly Ile Thr Gly Pro Glu Gly His Val
210 215 220
Leu Ser Arg Pro Glu Glu Val Glu Ala Glu Ala Val Asn Arg Ala Ile
225 230 235 240
Thr Ile Ala Asn Gln Thr Asn Cys Pro Leu Tyr Ile Thr Lys Val Met
245 250 255
Ser Lys Ser Ser Ala Glu Val Ile Ala Gln Ala Arg Lys Lys Gly Thr
260 265 270
Val Val Tyr Gly Glu Pro Ile Thr Ala Ser Leu Gly Thr Asp Gly Ser
275 280 285
His Tyr Trp Ser Lys Asn Trp Ala Lys Ala Ala Ala Phe Val Thr Ser
290 295 300
Pro Pro Leu Ser Pro Asp Pro Thr Thr Pro Asp Phe Leu Asn Ser Leu
305 310 315 320
Leu Ser Cys Gly Asp Leu Gln Val Thr Gly Ser Ala His Cys Thr Phe
325 330 335
Asn Thr Ala Gln Lys Ala Val Gly Lys Asp Asn Phe Thr Leu Ile Pro
340 345 350
Glu Gly Thr Asn Gly Thr Glu Glu Arg Met Ser Val Ile Trp Asp Lys
355 360 365
Ala Val Val Thr Gly Lys Met Asp Glu Asn Gln Phe Val Ala Val Thr
370 375 380
Ser Thr Asn Ala Ala Lys Val Phe Asn Leu Tyr Pro Arg Lys Gly Arg
385 390 395 400
Ile Ala Val Gly Ser Asp Ala Asp Leu Val Ile Trp Asp Pro Asp Ser
405 410 415
Val Lys Thr Ile Ser Ala Lys Thr His Asn Ser Ser Leu Glu Tyr Asn
420 425 430
Ile Phe Glu Gly Met Glu Cys Arg Gly Ser Pro Leu Val Val Ile Ser
435 440 445
Gln Gly Lys Ile Val Leu Glu Asp Gly Thr Leu His Val Thr Glu Gly
450 455 460
Ser Gly Arg Tyr Ile Pro Arg Lys Pro Phe Pro Asp Phe Val Tyr Lys
465 470 475 480
Arg Ile Lys Ala Arg Ser Arg Leu Ala Glu Leu Arg Gly Val Pro Arg
485 490 495
Gly Leu Tyr Asp Gly Pro Val Cys Glu Val Ser Val Thr Pro Lys Thr
500 505 510
Val Thr Pro Ala Ser Ser Ala Lys Thr Ser Pro Ala Lys Gln Gln Ala
515 520 525
Pro Pro Val Arg Asn Leu His Gln Ser Gly Phe Ser Leu Ser Gly Ala
530 535 540
Gln Ile Asp Asp Asn Ile Pro Arg Arg Thr Thr Gln Arg Ile Val Ala
545 550 555 560
Pro Pro Gly Gly Arg Ala Asn Ile Thr Ser Leu Gly
565 570
<210> 57
<211> 4646
<212> PRT
<213> 智人
<400> 57
Met Ser Glu Pro Gly Gly Gly Gly Gly Glu Asp Gly Ser Ala Gly Leu
1 5 10 15
Glu Val Ser Ala Val Gln Asn Val Ala Asp Val Ser Val Leu Gln Lys
20 25 30
His Leu Arg Lys Leu Val Pro Leu Leu Leu Glu Asp Gly Gly Glu Ala
35 40 45
Pro Ala Ala Leu Glu Ala Ala Leu Glu Glu Lys Ser Ala Leu Glu Gln
50 55 60
Met Arg Lys Phe Leu Ser Asp Pro Gln Val His Thr Val Leu Val Glu
65 70 75 80
Arg Ser Thr Leu Lys Glu Asp Val Gly Asp Glu Gly Glu Glu Glu Lys
85 90 95
Glu Phe Ile Ser Tyr Asn Ile Asn Ile Asp Ile His Tyr Gly Val Lys
100 105 110
Ser Asn Ser Leu Ala Phe Ile Lys Arg Thr Pro Val Ile Asp Ala Asp
115 120 125
Lys Pro Val Ser Ser Gln Leu Arg Val Leu Thr Leu Ser Glu Asp Ser
130 135 140
Pro Tyr Glu Thr Leu His Ser Phe Ile Ser Asn Ala Val Ala Pro Phe
145 150 155 160
Phe Lys Ser Tyr Ile Arg Glu Ser Gly Lys Ala Asp Arg Asp Gly Asp
165 170 175
Lys Met Ala Pro Ser Val Glu Lys Lys Ile Ala Glu Leu Glu Met Gly
180 185 190
Leu Leu His Leu Gln Gln Asn Ile Glu Ile Pro Glu Ile Ser Leu Pro
195 200 205
Ile His Pro Met Ile Thr Asn Val Ala Lys Gln Cys Tyr Glu Arg Gly
210 215 220
Glu Lys Pro Lys Val Thr Asp Phe Gly Asp Lys Val Glu Asp Pro Thr
225 230 235 240
Phe Leu Asn Gln Leu Gln Ser Gly Val Asn Arg Trp Ile Arg Glu Ile
245 250 255
Gln Lys Val Thr Lys Leu Asp Arg Asp Pro Ala Ser Gly Thr Ala Leu
260 265 270
Gln Glu Ile Ser Phe Trp Leu Asn Leu Glu Arg Ala Leu Tyr Arg Ile
275 280 285
Gln Glu Lys Arg Glu Ser Pro Glu Val Leu Leu Thr Leu Asp Ile Leu
290 295 300
Lys His Gly Lys Arg Phe His Ala Thr Val Ser Phe Asp Thr Asp Thr
305 310 315 320
Gly Leu Lys Gln Ala Leu Glu Thr Val Asn Asp Tyr Asn Pro Leu Met
325 330 335
Lys Asp Phe Pro Leu Asn Asp Leu Leu Ser Ala Thr Glu Leu Asp Lys
340 345 350
Ile Arg Gln Ala Leu Val Ala Ile Phe Thr His Leu Arg Lys Ile Arg
355 360 365
Asn Thr Lys Tyr Pro Ile Gln Arg Ala Leu Arg Leu Val Glu Ala Ile
370 375 380
Ser Arg Asp Leu Ser Ser Gln Leu Leu Lys Val Leu Gly Thr Arg Lys
385 390 395 400
Leu Met His Val Ala Tyr Glu Glu Phe Glu Lys Val Met Val Ala Cys
405 410 415
Phe Glu Val Phe Gln Thr Trp Asp Asp Glu Tyr Glu Lys Leu Gln Val
420 425 430
Leu Leu Arg Asp Ile Val Lys Arg Lys Arg Glu Glu Asn Leu Lys Met
435 440 445
Val Trp Arg Ile Asn Pro Ala His Arg Lys Leu Gln Ala Arg Leu Asp
450 455 460
Gln Met Arg Lys Phe Arg Arg Gln His Glu Gln Leu Arg Ala Val Ile
465 470 475 480
Val Arg Val Leu Arg Pro Gln Val Thr Ala Val Ala Gln Gln Asn Gln
485 490 495
Gly Glu Val Pro Glu Pro Gln Asp Met Lys Val Ala Glu Val Leu Phe
500 505 510
Asp Ala Ala Asp Ala Asn Ala Ile Glu Glu Val Asn Leu Ala Tyr Glu
515 520 525
Asn Val Lys Glu Val Asp Gly Leu Asp Val Ser Lys Glu Gly Thr Glu
530 535 540
Ala Trp Glu Ala Ala Met Lys Arg Tyr Asp Glu Arg Ile Asp Arg Val
545 550 555 560
Glu Thr Arg Ile Thr Ala Arg Leu Arg Asp Gln Leu Gly Thr Ala Lys
565 570 575
Asn Ala Asn Glu Met Phe Arg Ile Phe Ser Arg Phe Asn Ala Leu Phe
580 585 590
Val Arg Pro His Ile Arg Gly Ala Ile Arg Glu Tyr Gln Thr Gln Leu
595 600 605
Ile Gln Arg Val Lys Asp Asp Ile Glu Ser Leu His Asp Lys Phe Lys
610 615 620
Val Gln Tyr Pro Gln Ser Gln Ala Cys Lys Met Ser His Val Arg Asp
625 630 635 640
Leu Pro Pro Val Ser Gly Ser Ile Ile Trp Ala Lys Gln Ile Asp Arg
645 650 655
Gln Leu Thr Ala Tyr Met Lys Arg Val Glu Asp Val Leu Gly Lys Gly
660 665 670
Trp Glu Asn His Val Glu Gly Gln Lys Leu Lys Gln Asp Gly Asp Ser
675 680 685
Phe Arg Met Lys Leu Asn Thr Gln Glu Ile Phe Asp Asp Trp Ala Arg
690 695 700
Lys Val Gln Gln Arg Asn Leu Gly Val Ser Gly Arg Ile Phe Thr Ile
705 710 715 720
Glu Ser Thr Arg Val Arg Gly Arg Thr Gly Asn Val Leu Lys Leu Lys
725 730 735
Val Asn Phe Leu Pro Glu Ile Ile Thr Leu Ser Lys Glu Val Arg Asn
740 745 750
Leu Lys Trp Leu Gly Phe Arg Val Pro Leu Ala Ile Val Asn Lys Ala
755 760 765
His Gln Ala Asn Gln Leu Tyr Pro Phe Ala Ile Ser Leu Ile Glu Ser
770 775 780
Val Arg Thr Tyr Glu Arg Thr Cys Glu Lys Val Glu Glu Arg Asn Thr
785 790 795 800
Ile Ser Leu Leu Val Ala Gly Leu Lys Lys Glu Val Gln Ala Leu Ile
805 810 815
Ala Glu Gly Ile Ala Leu Val Trp Glu Ser Tyr Lys Leu Asp Pro Tyr
820 825 830
Val Gln Arg Leu Ala Glu Thr Val Phe Asn Phe Gln Glu Lys Val Asp
835 840 845
Asp Leu Leu Ile Ile Glu Glu Lys Ile Asp Leu Glu Val Arg Ser Leu
850 855 860
Glu Thr Cys Met Tyr Asp His Lys Thr Phe Ser Glu Ile Leu Asn Arg
865 870 875 880
Val Gln Lys Ala Val Asp Asp Leu Asn Leu His Ser Tyr Ser Asn Leu
885 890 895
Pro Ile Trp Val Asn Lys Leu Asp Met Glu Ile Glu Arg Ile Leu Gly
900 905 910
Val Arg Leu Gln Ala Gly Leu Arg Ala Trp Thr Gln Val Leu Leu Gly
915 920 925
Gln Ala Glu Asp Lys Ala Glu Val Asp Met Asp Thr Asp Ala Pro Gln
930 935 940
Val Ser His Lys Pro Gly Gly Glu Pro Lys Ile Lys Asn Val Val His
945 950 955 960
Glu Leu Arg Ile Thr Asn Gln Val Ile Tyr Leu Asn Pro Pro Ile Glu
965 970 975
Glu Cys Arg Tyr Lys Leu Tyr Gln Glu Met Phe Ala Trp Lys Met Val
980 985 990
Val Leu Ser Leu Pro Arg Ile Gln Ser Gln Arg Tyr Gln Val Gly Val
995 1000 1005
His Tyr Glu Leu Thr Glu Glu Glu Lys Phe Tyr Arg Asn Ala Leu
1010 1015 1020
Thr Arg Met Pro Asp Gly Pro Val Ala Leu Glu Glu Ser Tyr Ser
1025 1030 1035
Ala Val Met Gly Ile Val Ser Glu Val Glu Gln Tyr Val Lys Val
1040 1045 1050
Trp Leu Gln Tyr Gln Cys Leu Trp Asp Met Gln Ala Glu Asn Ile
1055 1060 1065
Tyr Asn Arg Leu Gly Glu Asp Leu Asn Lys Trp Gln Ala Leu Leu
1070 1075 1080
Val Gln Ile Arg Lys Ala Arg Gly Thr Phe Asp Asn Ala Glu Thr
1085 1090 1095
Lys Lys Glu Phe Gly Pro Val Val Ile Asp Tyr Gly Lys Val Gln
1100 1105 1110
Ser Lys Val Asn Leu Lys Tyr Asp Ser Trp His Lys Glu Val Leu
1115 1120 1125
Ser Lys Phe Gly Gln Met Leu Gly Ser Asn Met Thr Glu Phe His
1130 1135 1140
Ser Gln Ile Ser Lys Ser Arg Gln Glu Leu Glu Gln His Ser Val
1145 1150 1155
Asp Thr Ala Ser Thr Ser Asp Ala Val Thr Phe Ile Thr Tyr Val
1160 1165 1170
Gln Ser Leu Lys Arg Lys Ile Lys Gln Phe Glu Lys Gln Val Glu
1175 1180 1185
Leu Tyr Arg Asn Gly Gln Arg Leu Leu Glu Lys Gln Arg Phe Gln
1190 1195 1200
Phe Pro Pro Ser Trp Leu Tyr Ile Asp Asn Ile Glu Gly Glu Trp
1205 1210 1215
Gly Ala Phe Asn Asp Ile Met Arg Arg Lys Asp Ser Ala Ile Gln
1220 1225 1230
Gln Gln Val Ala Asn Leu Gln Met Lys Ile Val Gln Glu Asp Arg
1235 1240 1245
Ala Val Glu Ser Arg Thr Thr Asp Leu Leu Thr Asp Trp Glu Lys
1250 1255 1260
Thr Lys Pro Val Thr Gly Asn Leu Arg Pro Glu Glu Ala Leu Gln
1265 1270 1275
Ala Leu Thr Ile Tyr Glu Gly Lys Phe Gly Arg Leu Lys Asp Asp
1280 1285 1290
Arg Glu Lys Cys Ala Lys Ala Lys Glu Ala Leu Glu Leu Thr Asp
1295 1300 1305
Thr Gly Leu Leu Ser Gly Ser Glu Glu Arg Val Gln Val Ala Leu
1310 1315 1320
Glu Glu Leu Gln Asp Leu Lys Gly Val Trp Ser Glu Leu Ser Lys
1325 1330 1335
Val Trp Glu Gln Ile Asp Gln Met Lys Glu Gln Pro Trp Val Ser
1340 1345 1350
Val Gln Pro Arg Lys Leu Arg Gln Asn Leu Asp Ala Leu Leu Asn
1355 1360 1365
Gln Leu Lys Ser Phe Pro Ala Arg Leu Arg Gln Tyr Ala Ser Tyr
1370 1375 1380
Glu Phe Val Gln Arg Leu Leu Lys Gly Tyr Met Lys Ile Asn Met
1385 1390 1395
Leu Val Ile Glu Leu Lys Ser Glu Ala Leu Lys Asp Arg His Trp
1400 1405 1410
Lys Gln Leu Met Lys Arg Leu His Val Asn Trp Val Val Ser Glu
1415 1420 1425
Leu Thr Leu Gly Gln Ile Trp Asp Val Asp Leu Gln Lys Asn Glu
1430 1435 1440
Ala Ile Val Lys Asp Val Leu Leu Val Ala Gln Gly Glu Met Ala
1445 1450 1455
Leu Glu Glu Phe Leu Lys Gln Ile Arg Glu Val Trp Asn Thr Tyr
1460 1465 1470
Glu Leu Asp Leu Val Asn Tyr Gln Asn Lys Cys Arg Leu Ile Arg
1475 1480 1485
Gly Trp Asp Asp Leu Phe Asn Lys Val Lys Glu His Ile Asn Ser
1490 1495 1500
Val Ser Ala Met Lys Leu Ser Pro Tyr Tyr Lys Val Phe Glu Glu
1505 1510 1515
Asp Ala Leu Ser Trp Glu Asp Lys Leu Asn Arg Ile Met Ala Leu
1520 1525 1530
Phe Asp Val Trp Ile Asp Val Gln Arg Arg Trp Val Tyr Leu Glu
1535 1540 1545
Gly Ile Phe Thr Gly Ser Ala Asp Ile Lys His Leu Leu Pro Val
1550 1555 1560
Glu Thr Gln Arg Phe Gln Ser Ile Ser Thr Glu Phe Leu Ala Leu
1565 1570 1575
Met Lys Lys Val Ser Lys Ser Pro Leu Val Met Asp Val Leu Asn
1580 1585 1590
Ile Gln Gly Val Gln Arg Ser Leu Glu Arg Leu Ala Asp Leu Leu
1595 1600 1605
Gly Lys Ile Gln Lys Ala Leu Gly Glu Tyr Leu Glu Arg Glu Arg
1610 1615 1620
Ser Ser Phe Pro Arg Phe Tyr Phe Val Gly Asp Glu Asp Leu Leu
1625 1630 1635
Glu Ile Ile Gly Asn Ser Lys Asn Val Ala Lys Leu Gln Lys His
1640 1645 1650
Phe Lys Lys Met Phe Ala Gly Val Ser Ser Ile Ile Leu Asn Glu
1655 1660 1665
Asp Asn Ser Val Val Leu Gly Ile Ser Ser Arg Glu Gly Glu Glu
1670 1675 1680
Val Met Phe Lys Thr Pro Val Ser Ile Thr Glu His Pro Lys Ile
1685 1690 1695
Asn Glu Trp Leu Thr Leu Val Glu Lys Glu Met Arg Val Thr Leu
1700 1705 1710
Ala Lys Leu Leu Ala Glu Ser Val Thr Glu Val Glu Ile Phe Gly
1715 1720 1725
Lys Ala Thr Ser Ile Asp Pro Asn Thr Tyr Ile Thr Trp Ile Asp
1730 1735 1740
Lys Tyr Gln Ala Gln Leu Val Val Leu Ser Ala Gln Ile Ala Trp
1745 1750 1755
Ser Glu Asn Val Glu Thr Ala Leu Ser Ser Met Gly Gly Gly Gly
1760 1765 1770
Asp Ala Ala Pro Leu His Ser Val Leu Ser Asn Val Glu Val Thr
1775 1780 1785
Leu Asn Val Leu Ala Asp Ser Val Leu Met Glu Gln Pro Pro Leu
1790 1795 1800
Arg Arg Arg Lys Leu Glu His Leu Ile Thr Glu Leu Val His Gln
1805 1810 1815
Arg Asp Val Thr Arg Ser Leu Ile Lys Ser Lys Ile Asp Asn Ala
1820 1825 1830
Lys Ser Phe Glu Trp Leu Ser Gln Met Arg Phe Tyr Phe Asp Pro
1835 1840 1845
Lys Gln Thr Asp Val Leu Gln Gln Leu Ser Ile Gln Met Ala Asn
1850 1855 1860
Ala Lys Phe Asn Tyr Gly Phe Glu Tyr Leu Gly Val Gln Asp Lys
1865 1870 1875
Leu Val Gln Thr Pro Leu Thr Asp Arg Cys Tyr Leu Thr Met Thr
1880 1885 1890
Gln Ala Leu Glu Ala Arg Leu Gly Gly Ser Pro Phe Gly Pro Ala
1895 1900 1905
Gly Thr Gly Lys Thr Glu Ser Val Lys Ala Leu Gly His Gln Leu
1910 1915 1920
Gly Arg Phe Val Leu Val Phe Asn Cys Asp Glu Thr Phe Asp Phe
1925 1930 1935
Gln Ala Met Gly Arg Ile Phe Val Gly Leu Cys Gln Val Gly Ala
1940 1945 1950
Trp Gly Cys Phe Asp Glu Phe Asn Arg Leu Glu Glu Arg Met Leu
1955 1960 1965
Ser Ala Val Ser Gln Gln Val Gln Cys Ile Gln Glu Ala Leu Arg
1970 1975 1980
Glu His Ser Asn Pro Asn Tyr Asp Lys Thr Ser Ala Pro Ile Thr
1985 1990 1995
Cys Glu Leu Leu Asn Lys Gln Val Lys Val Ser Pro Asp Met Ala
2000 2005 2010
Ile Phe Ile Thr Met Asn Pro Gly Tyr Ala Gly Arg Ser Asn Leu
2015 2020 2025
Pro Asp Asn Leu Lys Lys Leu Phe Arg Ser Leu Ala Met Thr Lys
2030 2035 2040
Pro Asp Arg Gln Leu Ile Ala Gln Val Met Leu Tyr Ser Gln Gly
2045 2050 2055
Phe Arg Thr Ala Glu Val Leu Ala Asn Lys Ile Val Pro Phe Phe
2060 2065 2070
Lys Leu Cys Asp Glu Gln Leu Ser Ser Gln Ser His Tyr Asp Phe
2075 2080 2085
Gly Leu Arg Ala Leu Lys Ser Val Leu Val Ser Ala Gly Asn Val
2090 2095 2100
Lys Arg Glu Arg Ile Gln Lys Ile Lys Arg Glu Lys Glu Glu Arg
2105 2110 2115
Gly Glu Ala Val Asp Glu Gly Glu Ile Ala Glu Asn Leu Pro Glu
2120 2125 2130
Gln Glu Ile Leu Ile Gln Ser Val Cys Glu Thr Met Val Pro Lys
2135 2140 2145
Leu Val Ala Glu Asp Ile Pro Leu Leu Phe Ser Leu Leu Ser Asp
2150 2155 2160
Val Phe Pro Gly Val Gln Tyr His Arg Gly Glu Met Thr Ala Leu
2165 2170 2175
Arg Glu Glu Leu Lys Lys Val Cys Gln Glu Met Tyr Leu Thr Tyr
2180 2185 2190
Gly Asp Gly Glu Glu Val Gly Gly Met Trp Val Glu Lys Val Leu
2195 2200 2205
Gln Leu Tyr Gln Ile Thr Gln Ile Asn His Gly Leu Met Met Val
2210 2215 2220
Gly Pro Ser Gly Ser Gly Lys Ser Met Ala Trp Arg Val Leu Leu
2225 2230 2235
Lys Ala Leu Glu Arg Leu Glu Gly Val Glu Gly Val Ala His Ile
2240 2245 2250
Ile Asp Pro Lys Ala Ile Ser Lys Asp His Leu Tyr Gly Thr Leu
2255 2260 2265
Asp Pro Asn Thr Arg Glu Trp Thr Asp Gly Leu Phe Thr His Val
2270 2275 2280
Leu Arg Lys Ile Ile Asp Ser Val Arg Gly Glu Leu Gln Lys Arg
2285 2290 2295
Gln Trp Ile Val Phe Asp Gly Asp Val Asp Pro Glu Trp Val Glu
2300 2305 2310
Asn Leu Asn Ser Val Leu Asp Asp Asn Lys Leu Leu Thr Leu Pro
2315 2320 2325
Asn Gly Glu Arg Leu Ser Leu Pro Pro Asn Val Arg Ile Met Phe
2330 2335 2340
Glu Val Gln Asp Leu Lys Tyr Ala Thr Leu Ala Thr Val Ser Arg
2345 2350 2355
Cys Gly Met Val Trp Phe Ser Glu Asp Val Leu Ser Thr Asp Met
2360 2365 2370
Ile Phe Asn Asn Phe Leu Ala Arg Leu Arg Ser Ile Pro Leu Asp
2375 2380 2385
Glu Gly Glu Asp Glu Ala Gln Arg Arg Arg Lys Gly Lys Glu Asp
2390 2395 2400
Glu Gly Glu Glu Ala Ala Ser Pro Met Leu Gln Ile Gln Arg Asp
2405 2410 2415
Ala Ala Thr Ile Met Gln Pro Tyr Phe Thr Ser Asn Gly Leu Val
2420 2425 2430
Thr Lys Ala Leu Glu His Ala Phe Gln Leu Glu His Ile Met Asp
2435 2440 2445
Leu Thr Arg Leu Arg Cys Leu Gly Ser Leu Phe Ser Met Leu His
2450 2455 2460
Gln Ala Cys Arg Asn Val Ala Gln Tyr Asn Ala Asn His Pro Asp
2465 2470 2475
Phe Pro Met Gln Ile Glu Gln Leu Glu Arg Tyr Ile Gln Arg Tyr
2480 2485 2490
Leu Val Tyr Ala Ile Leu Trp Ser Leu Ser Gly Asp Ser Arg Leu
2495 2500 2505
Lys Met Arg Ala Glu Leu Gly Glu Tyr Ile Arg Arg Ile Thr Thr
2510 2515 2520
Val Pro Leu Pro Thr Ala Pro Asn Ile Pro Ile Ile Asp Tyr Glu
2525 2530 2535
Val Ser Ile Ser Gly Glu Trp Ser Pro Trp Gln Ala Lys Val Pro
2540 2545 2550
Gln Ile Glu Val Glu Thr His Lys Val Ala Ala Pro Asp Val Val
2555 2560 2565
Val Pro Thr Leu Asp Thr Val Arg His Glu Ala Leu Leu Tyr Thr
2570 2575 2580
Trp Leu Ala Glu His Lys Pro Leu Val Leu Cys Gly Pro Pro Gly
2585 2590 2595
Ser Gly Lys Thr Met Thr Leu Phe Ser Ala Leu Arg Ala Leu Pro
2600 2605 2610
Asp Met Glu Val Val Gly Leu Asn Phe Ser Ser Ala Thr Thr Pro
2615 2620 2625
Glu Leu Leu Leu Lys Thr Phe Asp His Tyr Cys Glu Tyr Arg Arg
2630 2635 2640
Thr Pro Asn Gly Val Val Leu Ala Pro Val Gln Leu Gly Lys Trp
2645 2650 2655
Leu Val Leu Phe Cys Asp Glu Ile Asn Leu Pro Asp Met Asp Lys
2660 2665 2670
Tyr Gly Thr Gln Arg Val Ile Ser Phe Ile Arg Gln Met Val Glu
2675 2680 2685
His Gly Gly Phe Tyr Arg Thr Ser Asp Gln Thr Trp Val Lys Leu
2690 2695 2700
Glu Arg Ile Gln Phe Val Gly Ala Cys Asn Pro Pro Thr Asp Pro
2705 2710 2715
Gly Arg Lys Pro Leu Ser His Arg Phe Leu Arg His Val Pro Val
2720 2725 2730
Val Tyr Val Asp Tyr Pro Gly Pro Ala Ser Leu Thr Gln Ile Tyr
2735 2740 2745
Gly Thr Phe Asn Arg Ala Met Leu Arg Leu Ile Pro Ser Leu Arg
2750 2755 2760
Thr Tyr Ala Glu Pro Leu Thr Ala Ala Met Val Glu Phe Tyr Thr
2765 2770 2775
Met Ser Gln Glu Arg Phe Thr Gln Asp Thr Gln Pro His Tyr Ile
2780 2785 2790
Tyr Ser Pro Arg Glu Met Thr Arg Trp Val Arg Gly Ile Phe Glu
2795 2800 2805
Ala Leu Arg Pro Leu Glu Thr Leu Pro Val Glu Gly Leu Ile Arg
2810 2815 2820
Ile Trp Ala His Glu Ala Leu Arg Leu Phe Gln Asp Arg Leu Val
2825 2830 2835
Glu Asp Glu Glu Arg Arg Trp Thr Asp Glu Asn Ile Asp Thr Val
2840 2845 2850
Ala Leu Lys His Phe Pro Asn Ile Asp Arg Glu Lys Ala Met Ser
2855 2860 2865
Arg Pro Ile Leu Tyr Ser Asn Trp Leu Ser Lys Asp Tyr Ile Pro
2870 2875 2880
Val Asp Gln Glu Glu Leu Arg Asp Tyr Val Lys Ala Arg Leu Lys
2885 2890 2895
Val Phe Tyr Glu Glu Glu Leu Asp Val Pro Leu Val Leu Phe Asn
2900 2905 2910
Glu Val Leu Asp His Val Leu Arg Ile Asp Arg Ile Phe Arg Gln
2915 2920 2925
Pro Gln Gly His Leu Leu Leu Ile Gly Val Ser Gly Ala Gly Lys
2930 2935 2940
Thr Thr Leu Ser Arg Phe Val Ala Trp Met Asn Gly Leu Ser Val
2945 2950 2955
Tyr Gln Ile Lys Val His Arg Lys Tyr Thr Gly Glu Asp Phe Asp
2960 2965 2970
Glu Asp Leu Arg Thr Val Leu Arg Arg Ser Gly Cys Lys Asn Glu
2975 2980 2985
Lys Ile Ala Phe Ile Met Asp Glu Ser Asn Val Leu Asp Ser Gly
2990 2995 3000
Phe Leu Glu Arg Met Asn Thr Leu Leu Ala Asn Gly Glu Val Pro
3005 3010 3015
Gly Leu Phe Glu Gly Asp Glu Tyr Ala Thr Leu Met Thr Gln Cys
3020 3025 3030
Lys Glu Gly Ala Gln Lys Glu Gly Leu Met Leu Asp Ser His Glu
3035 3040 3045
Glu Leu Tyr Lys Trp Phe Thr Ser Gln Val Ile Arg Asn Leu His
3050 3055 3060
Val Val Phe Thr Met Asn Pro Ser Ser Glu Gly Leu Lys Asp Arg
3065 3070 3075
Ala Ala Thr Ser Pro Ala Leu Phe Asn Arg Cys Val Leu Asn Trp
3080 3085 3090
Phe Gly Asp Trp Ser Thr Glu Ala Leu Tyr Gln Val Gly Lys Glu
3095 3100 3105
Phe Thr Ser Lys Met Asp Leu Glu Lys Pro Asn Tyr Ile Val Pro
3110 3115 3120
Asp Tyr Met Pro Val Val Tyr Asp Lys Leu Pro Gln Pro Pro Ser
3125 3130 3135
His Arg Glu Ala Ile Val Asn Ser Cys Val Phe Val His Gln Thr
3140 3145 3150
Leu His Gln Ala Asn Ala Arg Leu Ala Lys Arg Gly Gly Arg Thr
3155 3160 3165
Met Ala Ile Thr Pro Arg His Tyr Leu Asp Phe Ile Asn His Tyr
3170 3175 3180
Ala Asn Leu Phe His Glu Lys Arg Ser Glu Leu Glu Glu Gln Gln
3185 3190 3195
Met His Leu Asn Val Gly Leu Arg Lys Ile Lys Glu Thr Val Asp
3200 3205 3210
Gln Val Glu Glu Leu Arg Arg Asp Leu Arg Ile Lys Ser Gln Glu
3215 3220 3225
Leu Glu Val Lys Asn Ala Ala Ala Asn Asp Lys Leu Lys Lys Met
3230 3235 3240
Val Lys Asp Gln Gln Glu Ala Glu Lys Lys Lys Val Met Ser Gln
3245 3250 3255
Glu Ile Gln Glu Gln Leu His Lys Gln Gln Glu Val Ile Ala Asp
3260 3265 3270
Lys Gln Met Ser Val Lys Glu Asp Leu Asp Lys Val Glu Pro Ala
3275 3280 3285
Val Ile Glu Ala Gln Asn Ala Val Lys Ser Ile Lys Lys Gln His
3290 3295 3300
Leu Val Glu Val Arg Ser Met Ala Asn Pro Pro Ala Ala Val Lys
3305 3310 3315
Leu Ala Leu Glu Ser Ile Cys Leu Leu Leu Gly Glu Ser Thr Thr
3320 3325 3330
Asp Trp Lys Gln Ile Arg Ser Ile Ile Met Arg Glu Asn Phe Ile
3335 3340 3345
Pro Thr Ile Val Asn Phe Ser Ala Glu Glu Ile Ser Asp Ala Ile
3350 3355 3360
Arg Glu Lys Met Lys Lys Asn Tyr Met Ser Asn Pro Ser Tyr Asn
3365 3370 3375
Tyr Glu Ile Val Asn Arg Ala Ser Leu Ala Cys Gly Pro Met Val
3380 3385 3390
Lys Trp Ala Ile Ala Gln Leu Asn Tyr Ala Asp Met Leu Lys Arg
3395 3400 3405
Val Glu Pro Leu Arg Asn Glu Leu Gln Lys Leu Glu Asp Asp Ala
3410 3415 3420
Lys Asp Asn Gln Gln Lys Ala Asn Glu Val Glu Gln Met Ile Arg
3425 3430 3435
Asp Leu Glu Ala Ser Ile Ala Arg Tyr Lys Glu Glu Tyr Ala Val
3440 3445 3450
Leu Ile Ser Glu Ala Gln Ala Ile Lys Ala Asp Leu Ala Ala Val
3455 3460 3465
Glu Ala Lys Val Asn Arg Ser Thr Ala Leu Leu Lys Ser Leu Ser
3470 3475 3480
Ala Glu Arg Glu Arg Trp Glu Lys Thr Ser Glu Thr Phe Lys Asn
3485 3490 3495
Gln Met Ser Thr Ile Ala Gly Asp Cys Leu Leu Ser Ala Ala Phe
3500 3505 3510
Ile Ala Tyr Ala Gly Tyr Phe Asp Gln Gln Met Arg Gln Asn Leu
3515 3520 3525
Phe Thr Thr Trp Ser His His Leu Gln Gln Ala Asn Ile Gln Phe
3530 3535 3540
Arg Thr Asp Ile Ala Arg Thr Glu Tyr Leu Ser Asn Ala Asp Glu
3545 3550 3555
Arg Leu Arg Trp Gln Ala Ser Ser Leu Pro Ala Asp Asp Leu Cys
3560 3565 3570
Thr Glu Asn Ala Ile Met Leu Lys Arg Phe Asn Arg Tyr Pro Leu
3575 3580 3585
Ile Ile Asp Pro Ser Gly Gln Ala Thr Glu Phe Ile Met Asn Glu
3590 3595 3600
Tyr Lys Asp Arg Lys Ile Thr Arg Thr Ser Phe Leu Asp Asp Ala
3605 3610 3615
Phe Arg Lys Asn Leu Glu Ser Ala Leu Arg Phe Gly Asn Pro Leu
3620 3625 3630
Leu Val Gln Asp Val Glu Ser Tyr Asp Pro Val Leu Asn Pro Val
3635 3640 3645
Leu Asn Arg Glu Val Arg Arg Thr Gly Gly Arg Val Leu Ile Thr
3650 3655 3660
Leu Gly Asp Gln Asp Ile Asp Leu Ser Pro Ser Phe Val Ile Phe
3665 3670 3675
Leu Ser Thr Arg Asp Pro Thr Val Glu Phe Pro Pro Asp Leu Cys
3680 3685 3690
Ser Arg Val Thr Phe Val Asn Phe Thr Val Thr Arg Ser Ser Leu
3695 3700 3705
Gln Ser Gln Cys Leu Asn Glu Val Leu Lys Ala Glu Arg Pro Asp
3710 3715 3720
Val Asp Glu Lys Arg Ser Asp Leu Leu Lys Leu Gln Gly Glu Phe
3725 3730 3735
Gln Leu Arg Leu Arg Gln Leu Glu Lys Ser Leu Leu Gln Ala Leu
3740 3745 3750
Asn Glu Val Lys Gly Arg Ile Leu Asp Asp Asp Thr Ile Ile Thr
3755 3760 3765
Thr Leu Glu Asn Leu Lys Arg Glu Ala Ala Glu Val Thr Arg Lys
3770 3775 3780
Val Glu Glu Thr Asp Ile Val Met Gln Glu Val Glu Thr Val Ser
3785 3790 3795
Gln Gln Tyr Leu Pro Leu Ser Thr Ala Cys Ser Ser Ile Tyr Phe
3800 3805 3810
Thr Met Glu Ser Leu Lys Gln Ile His Phe Leu Tyr Gln Tyr Ser
3815 3820 3825
Leu Gln Phe Phe Leu Asp Ile Tyr His Asn Val Leu Tyr Glu Asn
3830 3835 3840
Pro Asn Leu Lys Gly Val Thr Asp His Thr Gln Arg Leu Ser Ile
3845 3850 3855
Ile Thr Lys Asp Leu Phe Gln Val Ala Phe Asn Arg Val Ala Arg
3860 3865 3870
Gly Met Leu His Gln Asp His Ile Thr Phe Ala Met Leu Leu Ala
3875 3880 3885
Arg Ile Lys Leu Lys Gly Thr Val Gly Glu Pro Thr Tyr Asp Ala
3890 3895 3900
Glu Phe Gln His Phe Leu Arg Gly Asn Glu Ile Val Leu Ser Ala
3905 3910 3915
Gly Ser Thr Pro Arg Ile Gln Gly Leu Thr Val Glu Gln Ala Glu
3920 3925 3930
Ala Val Val Arg Leu Ser Cys Leu Pro Ala Phe Lys Asp Leu Ile
3935 3940 3945
Ala Lys Val Gln Ala Asp Glu Gln Phe Gly Ile Trp Leu Asp Ser
3950 3955 3960
Ser Ser Pro Glu Gln Thr Val Pro Tyr Leu Trp Ser Glu Glu Thr
3965 3970 3975
Pro Ala Thr Pro Ile Gly Gln Ala Ile His Arg Leu Leu Leu Ile
3980 3985 3990
Gln Ala Phe Arg Pro Asp Arg Leu Leu Ala Met Ala His Met Phe
3995 4000 4005
Val Ser Thr Asn Leu Gly Glu Ser Phe Met Ser Ile Met Glu Gln
4010 4015 4020
Pro Leu Asp Leu Thr His Ile Val Gly Thr Glu Val Lys Pro Asn
4025 4030 4035
Thr Pro Val Leu Met Cys Ser Val Pro Gly Tyr Asp Ala Ser Gly
4040 4045 4050
His Val Glu Asp Leu Ala Ala Glu Gln Asn Thr Gln Ile Thr Ser
4055 4060 4065
Ile Ala Ile Gly Ser Ala Glu Gly Phe Asn Gln Ala Asp Lys Ala
4070 4075 4080
Ile Asn Thr Ala Val Lys Ser Gly Arg Trp Val Met Leu Lys Asn
4085 4090 4095
Val His Leu Ala Pro Gly Trp Leu Met Gln Leu Glu Lys Lys Leu
4100 4105 4110
His Ser Leu Gln Pro His Ala Cys Phe Arg Leu Phe Leu Thr Met
4115 4120 4125
Glu Ile Asn Pro Lys Val Pro Val Asn Leu Leu Arg Ala Gly Arg
4130 4135 4140
Ile Phe Val Phe Glu Pro Pro Pro Gly Val Lys Ala Asn Met Leu
4145 4150 4155
Arg Thr Phe Ser Ser Ile Pro Val Ser Arg Ile Cys Lys Ser Pro
4160 4165 4170
Asn Glu Arg Ala Arg Leu Tyr Phe Leu Leu Ala Trp Phe His Ala
4175 4180 4185
Ile Ile Gln Glu Arg Leu Arg Tyr Ala Pro Leu Gly Trp Ser Lys
4190 4195 4200
Lys Tyr Glu Phe Gly Glu Ser Asp Leu Arg Ser Ala Cys Asp Thr
4205 4210 4215
Val Asp Thr Trp Leu Asp Asp Thr Ala Lys Gly Arg Gln Asn Ile
4220 4225 4230
Ser Pro Asp Lys Ile Pro Trp Ser Ala Leu Lys Thr Leu Met Ala
4235 4240 4245
Gln Ser Ile Tyr Gly Gly Arg Val Asp Asn Glu Phe Asp Gln Arg
4250 4255 4260
Leu Leu Asn Thr Phe Leu Glu Arg Leu Phe Thr Thr Arg Ser Phe
4265 4270 4275
Asp Ser Glu Phe Lys Leu Ala Cys Lys Val Asp Gly His Lys Asp
4280 4285 4290
Ile Gln Met Pro Asp Gly Ile Arg Arg Glu Glu Phe Val Gln Trp
4295 4300 4305
Val Glu Leu Leu Pro Asp Thr Gln Thr Pro Ser Trp Leu Gly Leu
4310 4315 4320
Pro Asn Asn Ala Glu Arg Val Leu Leu Thr Thr Gln Gly Val Asp
4325 4330 4335
Met Ile Ser Lys Met Leu Lys Met Gln Met Leu Glu Asp Glu Asp
4340 4345 4350
Asp Leu Ala Tyr Ala Glu Thr Glu Lys Lys Thr Arg Thr Asp Ser
4355 4360 4365
Thr Ser Asp Gly Arg Pro Ala Trp Met Arg Thr Leu His Thr Thr
4370 4375 4380
Ala Ser Asn Trp Leu His Leu Ile Pro Gln Thr Leu Ser His Leu
4385 4390 4395
Lys Arg Thr Val Glu Asn Ile Lys Asp Pro Leu Phe Arg Phe Phe
4400 4405 4410
Glu Arg Glu Val Lys Met Gly Ala Lys Leu Leu Gln Asp Val Arg
4415 4420 4425
Gln Asp Leu Ala Asp Val Val Gln Val Cys Glu Gly Lys Lys Lys
4430 4435 4440
Gln Thr Asn Tyr Leu Arg Thr Leu Ile Asn Glu Leu Val Lys Gly
4445 4450 4455
Ile Leu Pro Arg Ser Trp Ser His Tyr Thr Val Pro Ala Gly Met
4460 4465 4470
Thr Val Ile Gln Trp Val Ser Asp Phe Ser Glu Arg Ile Lys Gln
4475 4480 4485
Leu Gln Asn Ile Ser Leu Ala Ala Ala Ser Gly Gly Ala Lys Glu
4490 4495 4500
Leu Lys Asn Ile His Val Cys Leu Gly Gly Leu Phe Val Pro Glu
4505 4510 4515
Ala Tyr Ile Thr Ala Thr Arg Gln Tyr Val Ala Gln Ala Asn Ser
4520 4525 4530
Trp Ser Leu Glu Glu Leu Cys Leu Glu Val Asn Val Thr Thr Ser
4535 4540 4545
Gln Gly Ala Thr Leu Asp Ala Cys Ser Phe Gly Val Thr Gly Leu
4550 4555 4560
Lys Leu Gln Gly Ala Thr Cys Asn Asn Asn Lys Leu Ser Leu Ser
4565 4570 4575
Asn Ala Ile Ser Thr Ala Leu Pro Leu Thr Gln Leu Arg Trp Val
4580 4585 4590
Lys Gln Thr Asn Thr Glu Lys Lys Ala Ser Val Val Thr Leu Pro
4595 4600 4605
Val Tyr Leu Asn Phe Thr Arg Ala Asp Leu Ile Phe Thr Val Asp
4610 4615 4620
Phe Glu Ile Ala Thr Lys Glu Asp Pro Arg Ser Phe Tyr Glu Arg
4625 4630 4635
Gly Val Ala Val Leu Cys Thr Glu
4640 4645
<210> 58
<211> 328
<212> PRT
<213> 智人
<400> 58
Met Ala Ala Gly Ile Val Ala Ser Arg Arg Leu Arg Asp Leu Leu Thr
1 5 10 15
Arg Arg Leu Thr Gly Ser Asn Tyr Pro Gly Leu Ser Ile Ser Leu Arg
20 25 30
Leu Thr Gly Ser Ser Ala Gln Glu Glu Ala Ser Gly Val Ala Leu Gly
35 40 45
Glu Ala Pro Asp His Ser Tyr Glu Ser Leu Arg Val Thr Ser Ala Gln
50 55 60
Lys His Val Leu His Val Gln Leu Asn Arg Pro Asn Lys Arg Asn Ala
65 70 75 80
Met Asn Lys Val Phe Trp Arg Glu Met Val Glu Cys Phe Asn Lys Ile
85 90 95
Ser Arg Asp Ala Asp Cys Arg Ala Val Val Ile Ser Gly Ala Gly Lys
100 105 110
Met Phe Thr Ala Gly Ile Asp Leu Met Asp Met Ala Ser Asp Ile Leu
115 120 125
Gln Pro Lys Gly Asp Asp Val Ala Arg Ile Ser Trp Tyr Leu Arg Asp
130 135 140
Ile Ile Thr Arg Tyr Gln Glu Thr Phe Asn Val Ile Glu Arg Cys Pro
145 150 155 160
Lys Pro Val Ile Ala Ala Val His Gly Gly Cys Ile Gly Gly Gly Val
165 170 175
Asp Leu Val Thr Ala Cys Asp Ile Arg Tyr Cys Ala Gln Asp Ala Phe
180 185 190
Phe Gln Val Lys Glu Val Asp Val Gly Leu Ala Ala Asp Val Gly Thr
195 200 205
Leu Gln Arg Leu Pro Lys Val Ile Gly Asn Gln Ser Leu Val Asn Glu
210 215 220
Leu Ala Phe Thr Ala Arg Lys Met Met Ala Asp Glu Ala Leu Gly Ser
225 230 235 240
Gly Leu Val Ser Arg Val Phe Pro Asp Lys Glu Val Met Leu Asp Ala
245 250 255
Ala Leu Ala Leu Ala Ala Glu Ile Ser Ser Lys Ser Pro Val Ala Val
260 265 270
Gln Ser Thr Lys Val Asn Leu Leu Tyr Ser Arg Asp His Ser Val Ala
275 280 285
Glu Ser Leu Asn Tyr Val Ala Ser Trp Asn Met Ser Met Leu Gln Thr
290 295 300
Gln Asp Leu Val Lys Ser Val Gln Ala Thr Thr Glu Asn Lys Glu Leu
305 310 315 320
Lys Thr Val Thr Phe Ser Lys Leu
325
<210> 59
<211> 858
<212> PRT
<213> 智人
<400> 59
Met Val Asn Phe Thr Val Asp Gln Ile Arg Ala Ile Met Asp Lys Lys
1 5 10 15
Ala Asn Ile Arg Asn Met Ser Val Ile Ala His Val Asp His Gly Lys
20 25 30
Ser Thr Leu Thr Asp Ser Leu Val Cys Lys Ala Gly Ile Ile Ala Ser
35 40 45
Ala Arg Ala Gly Glu Thr Arg Phe Thr Asp Thr Arg Lys Asp Glu Gln
50 55 60
Glu Arg Cys Ile Thr Ile Lys Ser Thr Ala Ile Ser Leu Phe Tyr Glu
65 70 75 80
Leu Ser Glu Asn Asp Leu Asn Phe Ile Lys Gln Ser Lys Asp Gly Ala
85 90 95
Gly Phe Leu Ile Asn Leu Ile Asp Ser Pro Gly His Val Asp Phe Ser
100 105 110
Ser Glu Val Thr Ala Ala Leu Arg Val Thr Asp Gly Ala Leu Val Val
115 120 125
Val Asp Cys Val Ser Gly Val Cys Val Gln Thr Glu Thr Val Leu Arg
130 135 140
Gln Ala Ile Ala Glu Arg Ile Lys Pro Val Leu Met Met Asn Lys Met
145 150 155 160
Asp Arg Ala Leu Leu Glu Leu Gln Leu Glu Pro Glu Glu Leu Tyr Gln
165 170 175
Thr Phe Gln Arg Ile Val Glu Asn Val Asn Val Ile Ile Ser Thr Tyr
180 185 190
Gly Glu Gly Glu Ser Gly Pro Met Gly Asn Ile Met Ile Asp Pro Val
195 200 205
Leu Gly Thr Val Gly Phe Gly Ser Gly Leu His Gly Trp Ala Phe Thr
210 215 220
Leu Lys Gln Phe Ala Glu Met Tyr Val Ala Lys Phe Ala Ala Lys Gly
225 230 235 240
Glu Gly Gln Leu Gly Pro Ala Glu Arg Ala Lys Lys Val Glu Asp Met
245 250 255
Met Lys Lys Leu Trp Gly Asp Arg Tyr Phe Asp Pro Ala Asn Gly Lys
260 265 270
Phe Ser Lys Ser Ala Thr Ser Pro Glu Gly Lys Lys Leu Pro Arg Thr
275 280 285
Phe Cys Gln Leu Ile Leu Asp Pro Ile Phe Lys Val Phe Asp Ala Ile
290 295 300
Met Asn Phe Lys Lys Glu Glu Thr Ala Lys Leu Ile Glu Lys Leu Asp
305 310 315 320
Ile Lys Leu Asp Ser Glu Asp Lys Asp Lys Glu Gly Lys Pro Leu Leu
325 330 335
Lys Ala Val Met Arg Arg Trp Leu Pro Ala Gly Asp Ala Leu Leu Gln
340 345 350
Met Ile Thr Ile His Leu Pro Ser Pro Val Thr Ala Gln Lys Tyr Arg
355 360 365
Cys Glu Leu Leu Tyr Glu Gly Pro Pro Asp Asp Glu Ala Ala Met Gly
370 375 380
Ile Lys Ser Cys Asp Pro Lys Gly Pro Leu Met Met Tyr Ile Ser Lys
385 390 395 400
Met Val Pro Thr Ser Asp Lys Gly Arg Phe Tyr Ala Phe Gly Arg Val
405 410 415
Phe Ser Gly Leu Val Ser Thr Gly Leu Lys Val Arg Ile Met Gly Pro
420 425 430
Asn Tyr Thr Pro Gly Lys Lys Glu Asp Leu Tyr Leu Lys Pro Ile Gln
435 440 445
Arg Thr Ile Leu Met Met Gly Arg Tyr Val Glu Pro Ile Glu Asp Val
450 455 460
Pro Cys Gly Asn Ile Val Gly Leu Val Gly Val Asp Gln Phe Leu Val
465 470 475 480
Lys Thr Gly Thr Ile Thr Thr Phe Glu His Ala His Asn Met Arg Val
485 490 495
Met Lys Phe Ser Val Ser Pro Val Val Arg Val Ala Val Glu Ala Lys
500 505 510
Asn Pro Ala Asp Leu Pro Lys Leu Val Glu Gly Leu Lys Arg Leu Ala
515 520 525
Lys Ser Asp Pro Met Val Gln Cys Ile Ile Glu Glu Ser Gly Glu His
530 535 540
Ile Ile Ala Gly Ala Gly Glu Leu His Leu Glu Ile Cys Leu Lys Asp
545 550 555 560
Leu Glu Glu Asp His Ala Cys Ile Pro Ile Lys Lys Ser Asp Pro Val
565 570 575
Val Ser Tyr Arg Glu Thr Val Ser Glu Glu Ser Asn Val Leu Cys Leu
580 585 590
Ser Lys Ser Pro Asn Lys His Asn Arg Leu Tyr Met Lys Ala Arg Pro
595 600 605
Phe Pro Asp Gly Leu Ala Glu Asp Ile Asp Lys Gly Glu Val Ser Ala
610 615 620
Arg Gln Glu Leu Lys Gln Arg Ala Arg Tyr Leu Ala Glu Lys Tyr Glu
625 630 635 640
Trp Asp Val Ala Glu Ala Arg Lys Ile Trp Cys Phe Gly Pro Asp Gly
645 650 655
Thr Gly Pro Asn Ile Leu Thr Asp Ile Thr Lys Gly Val Gln Tyr Leu
660 665 670
Asn Glu Ile Lys Asp Ser Val Val Ala Gly Phe Gln Trp Ala Thr Lys
675 680 685
Glu Gly Ala Leu Cys Glu Glu Asn Met Arg Gly Val Arg Phe Asp Val
690 695 700
His Asp Val Thr Leu His Ala Asp Ala Ile His Arg Gly Gly Gly Gln
705 710 715 720
Ile Ile Pro Thr Ala Arg Arg Cys Leu Tyr Ala Ser Val Leu Thr Ala
725 730 735
Gln Pro Arg Leu Met Glu Pro Ile Tyr Leu Val Glu Ile Gln Cys Pro
740 745 750
Glu Gln Val Val Gly Gly Ile Tyr Gly Val Leu Asn Arg Lys Arg Gly
755 760 765
His Val Phe Glu Glu Ser Gln Val Ala Gly Thr Pro Met Phe Val Val
770 775 780
Lys Ala Tyr Leu Pro Val Asn Glu Ser Phe Gly Phe Thr Ala Asp Leu
785 790 795 800
Arg Ser Asn Thr Gly Gly Gln Ala Phe Pro Gln Cys Val Phe Asp His
805 810 815
Trp Gln Ile Leu Pro Gly Asp Pro Phe Asp Asn Ser Ser Arg Pro Ser
820 825 830
Gln Val Val Ala Glu Thr Arg Lys Arg Lys Gly Leu Lys Glu Gly Ile
835 840 845
Pro Ala Leu Asp Asn Phe Leu Asp Lys Leu
850 855
<210> 60
<211> 411
<212> PRT
<213> 智人
<400> 60
Met Ala Thr Thr Ala Thr Met Ala Thr Ser Gly Ser Ala Arg Lys Arg
1 5 10 15
Leu Leu Lys Glu Glu Asp Met Thr Lys Val Glu Phe Glu Thr Ser Glu
20 25 30
Glu Val Asp Val Thr Pro Thr Phe Asp Thr Met Gly Leu Arg Glu Asp
35 40 45
Leu Leu Arg Gly Ile Tyr Ala Tyr Gly Phe Glu Lys Pro Ser Ala Ile
50 55 60
Gln Gln Arg Ala Ile Lys Gln Ile Ile Lys Gly Arg Asp Val Ile Ala
65 70 75 80
Gln Ser Gln Ser Gly Thr Gly Lys Thr Ala Thr Phe Ser Ile Ser Val
85 90 95
Leu Gln Cys Leu Asp Ile Gln Val Arg Glu Thr Gln Ala Leu Ile Leu
100 105 110
Ala Pro Thr Arg Glu Leu Ala Val Gln Ile Gln Lys Gly Leu Leu Ala
115 120 125
Leu Gly Asp Tyr Met Asn Val Gln Cys His Ala Cys Ile Gly Gly Thr
130 135 140
Asn Val Gly Glu Asp Ile Arg Lys Leu Asp Tyr Gly Gln His Val Val
145 150 155 160
Ala Gly Thr Pro Gly Arg Val Phe Asp Met Ile Arg Arg Arg Ser Leu
165 170 175
Arg Thr Arg Ala Ile Lys Met Leu Val Leu Asp Glu Ala Asp Glu Met
180 185 190
Leu Asn Lys Gly Phe Lys Glu Gln Ile Tyr Asp Val Tyr Arg Tyr Leu
195 200 205
Pro Pro Ala Thr Gln Val Val Leu Ile Ser Ala Thr Leu Pro His Glu
210 215 220
Ile Leu Glu Met Thr Asn Lys Phe Met Thr Asp Pro Ile Arg Ile Leu
225 230 235 240
Val Lys Arg Asp Glu Leu Thr Leu Glu Gly Ile Lys Gln Phe Phe Val
245 250 255
Ala Val Glu Arg Glu Glu Trp Lys Phe Asp Thr Leu Cys Asp Leu Tyr
260 265 270
Asp Thr Leu Thr Ile Thr Gln Ala Val Ile Phe Cys Asn Thr Lys Arg
275 280 285
Lys Val Asp Trp Leu Thr Glu Lys Met Arg Glu Ala Asn Phe Thr Val
290 295 300
Ser Ser Met His Gly Asp Met Pro Gln Lys Glu Arg Glu Ser Ile Met
305 310 315 320
Lys Glu Phe Arg Ser Gly Ala Ser Arg Val Leu Ile Ser Thr Asp Val
325 330 335
Trp Ala Arg Gly Leu Asp Val Pro Gln Val Ser Leu Ile Ile Asn Tyr
340 345 350
Asp Leu Pro Asn Asn Arg Glu Leu Tyr Ile His Arg Ile Gly Arg Ser
355 360 365
Gly Arg Tyr Gly Arg Lys Gly Val Ala Ile Asn Phe Val Lys Asn Asp
370 375 380
Asp Ile Arg Ile Leu Arg Asp Ile Glu Gln Tyr Tyr Ser Thr Gln Ile
385 390 395 400
Asp Glu Met Pro Met Asn Val Ala Asp Leu Ile
405 410
<210> 61
<211> 434
<212> PRT
<213> 智人
<400> 61
Met Ser Ile Leu Lys Ile His Ala Arg Glu Ile Phe Asp Ser Arg Gly
1 5 10 15
Asn Pro Thr Val Glu Val Asp Leu Phe Thr Ser Lys Gly Leu Phe Arg
20 25 30
Ala Ala Val Pro Ser Gly Ala Ser Thr Gly Ile Tyr Glu Ala Leu Glu
35 40 45
Leu Arg Asp Asn Asp Lys Thr Arg Tyr Met Gly Lys Gly Val Ser Lys
50 55 60
Ala Val Glu His Ile Asn Lys Thr Ile Ala Pro Ala Leu Val Ser Lys
65 70 75 80
Lys Leu Asn Val Thr Glu Gln Glu Lys Ile Asp Lys Leu Met Ile Glu
85 90 95
Met Asp Gly Thr Glu Asn Lys Ser Lys Phe Gly Ala Asn Ala Ile Leu
100 105 110
Gly Val Ser Leu Ala Val Cys Lys Ala Gly Ala Val Glu Lys Gly Val
115 120 125
Pro Leu Tyr Arg His Ile Ala Asp Leu Ala Gly Asn Ser Glu Val Ile
130 135 140
Leu Pro Val Pro Ala Phe Asn Val Ile Asn Gly Gly Ser His Ala Gly
145 150 155 160
Asn Lys Leu Ala Met Gln Glu Phe Met Ile Leu Pro Val Gly Ala Ala
165 170 175
Asn Phe Arg Glu Ala Met Arg Ile Gly Ala Glu Val Tyr His Asn Leu
180 185 190
Lys Asn Val Ile Lys Glu Lys Tyr Gly Lys Asp Ala Thr Asn Val Gly
195 200 205
Asp Glu Gly Gly Phe Ala Pro Asn Ile Leu Glu Asn Lys Glu Gly Leu
210 215 220
Glu Leu Leu Lys Thr Ala Ile Gly Lys Ala Gly Tyr Thr Asp Lys Val
225 230 235 240
Val Ile Gly Met Asp Val Ala Ala Ser Glu Phe Phe Arg Ser Gly Lys
245 250 255
Tyr Asp Leu Asp Phe Lys Ser Pro Asp Asp Pro Ser Arg Tyr Ile Ser
260 265 270
Pro Asp Gln Leu Ala Asp Leu Tyr Lys Ser Phe Ile Lys Asp Tyr Pro
275 280 285
Val Val Ser Ile Glu Asp Pro Phe Asp Gln Asp Asp Trp Gly Ala Trp
290 295 300
Gln Lys Phe Thr Ala Ser Ala Gly Ile Gln Val Val Gly Asp Asp Leu
305 310 315 320
Thr Val Thr Asn Pro Lys Arg Ile Ala Lys Ala Val Asn Glu Lys Ser
325 330 335
Cys Asn Cys Leu Leu Leu Lys Val Asn Gln Ile Gly Ser Val Thr Glu
340 345 350
Ser Leu Gln Ala Cys Lys Leu Ala Gln Ala Asn Gly Trp Gly Val Met
355 360 365
Val Ser His Arg Ser Gly Glu Thr Glu Asp Thr Phe Ile Ala Asp Leu
370 375 380
Val Val Gly Leu Cys Thr Gly Gln Ile Lys Thr Gly Ala Pro Cys Arg
385 390 395 400
Ser Glu Arg Leu Ala Lys Tyr Asn Gln Leu Leu Arg Ile Glu Glu Glu
405 410 415
Leu Gly Ser Lys Ala Lys Phe Ala Gly Arg Asn Phe Arg Asn Pro Leu
420 425 430
Ala Lys
<210> 62
<211> 586
<212> PRT
<213> 智人
<400> 62
Met Pro Lys Pro Ile Asn Val Arg Val Thr Thr Met Asp Ala Glu Leu
1 5 10 15
Glu Phe Ala Ile Gln Pro Asn Thr Thr Gly Lys Gln Leu Phe Asp Gln
20 25 30
Val Val Lys Thr Ile Gly Leu Arg Glu Val Trp Tyr Phe Gly Leu His
35 40 45
Tyr Val Asp Asn Lys Gly Phe Pro Thr Trp Leu Lys Leu Asp Lys Lys
50 55 60
Val Ser Ala Gln Glu Val Arg Lys Glu Asn Pro Leu Gln Phe Lys Phe
65 70 75 80
Arg Ala Lys Phe Tyr Pro Glu Asp Val Ala Glu Glu Leu Ile Gln Asp
85 90 95
Ile Thr Gln Lys Leu Phe Phe Leu Gln Val Lys Glu Gly Ile Leu Ser
100 105 110
Asp Glu Ile Tyr Cys Pro Pro Glu Thr Ala Val Leu Leu Gly Ser Tyr
115 120 125
Ala Val Gln Ala Lys Phe Gly Asp Tyr Asn Lys Glu Val His Lys Ser
130 135 140
Gly Tyr Leu Ser Ser Glu Arg Leu Ile Pro Gln Arg Val Met Asp Gln
145 150 155 160
His Lys Leu Thr Arg Asp Gln Trp Glu Asp Arg Ile Gln Val Trp His
165 170 175
Ala Glu His Arg Gly Met Leu Lys Asp Asn Ala Met Leu Glu Tyr Leu
180 185 190
Lys Ile Ala Gln Asp Leu Glu Met Tyr Gly Ile Asn Tyr Phe Glu Ile
195 200 205
Lys Asn Lys Lys Gly Thr Asp Leu Trp Leu Gly Val Asp Ala Leu Gly
210 215 220
Leu Asn Ile Tyr Glu Lys Asp Asp Lys Leu Thr Pro Lys Ile Gly Phe
225 230 235 240
Pro Trp Ser Glu Ile Arg Asn Ile Ser Phe Asn Asp Lys Lys Phe Val
245 250 255
Ile Lys Pro Ile Asp Lys Lys Ala Pro Asp Phe Val Phe Tyr Ala Pro
260 265 270
Arg Leu Arg Ile Asn Lys Arg Ile Leu Gln Leu Cys Met Gly Asn His
275 280 285
Glu Leu Tyr Met Arg Arg Arg Lys Pro Asp Thr Ile Glu Val Gln Gln
290 295 300
Met Lys Ala Gln Ala Arg Glu Glu Lys His Gln Lys Gln Leu Glu Arg
305 310 315 320
Gln Gln Leu Glu Thr Glu Lys Lys Arg Arg Glu Thr Val Glu Arg Glu
325 330 335
Lys Glu Gln Met Met Arg Glu Lys Glu Glu Leu Met Leu Arg Leu Gln
340 345 350
Asp Tyr Glu Glu Lys Thr Lys Lys Ala Glu Arg Glu Leu Ser Glu Gln
355 360 365
Ile Gln Arg Ala Leu Gln Leu Glu Glu Glu Arg Lys Arg Ala Gln Glu
370 375 380
Glu Ala Glu Arg Leu Glu Ala Asp Arg Met Ala Ala Leu Arg Ala Lys
385 390 395 400
Glu Glu Leu Glu Arg Gln Ala Val Asp Gln Ile Lys Ser Gln Glu Gln
405 410 415
Leu Ala Ala Glu Leu Ala Glu Tyr Thr Ala Lys Ile Ala Leu Leu Glu
420 425 430
Glu Ala Arg Arg Arg Lys Glu Asp Glu Val Glu Glu Trp Gln His Arg
435 440 445
Ala Lys Glu Ala Gln Asp Asp Leu Val Lys Thr Lys Glu Glu Leu His
450 455 460
Leu Val Met Thr Ala Pro Pro Pro Pro Pro Pro Pro Val Tyr Glu Pro
465 470 475 480
Val Ser Tyr His Val Gln Glu Ser Leu Gln Asp Glu Gly Ala Glu Pro
485 490 495
Thr Gly Tyr Ser Ala Glu Leu Ser Ser Glu Gly Ile Arg Asp Asp Arg
500 505 510
Asn Glu Glu Lys Arg Ile Thr Glu Ala Glu Lys Asn Glu Arg Val Gln
515 520 525
Arg Gln Leu Leu Thr Leu Ser Ser Glu Leu Ser Gln Ala Arg Asp Glu
530 535 540
Asn Lys Arg Thr His Asn Asp Ile Ile His Asn Glu Asn Met Arg Gln
545 550 555 560
Gly Arg Asp Lys Tyr Lys Thr Leu Arg Gln Ile Arg Gln Gly Asn Thr
565 570 575
Lys Gln Arg Ile Asp Glu Phe Glu Ala Leu
580 585
<210> 63
<211> 697
<212> PRT
<213> 智人
<400> 63
Met Gly Pro Asp Arg Lys Glu Val Pro Leu Ser Arg Gly Thr Gln Ala
1 5 10 15
Val Val Val Gly Lys Gly Arg Gly Ala Pro Gly Asp Asp Ser Ser Met
20 25 30
Gly Gly Arg Pro Ser Ser Pro Leu Asp Lys Gln Gln Arg Gln His Leu
35 40 45
Arg Gly Gln Val Asp Thr Leu Leu Arg Asn Phe Leu Pro Cys Tyr Arg
50 55 60
Gly Gln Leu Ala Ala Ser Val Leu Arg Gln Ile Ser Arg Glu Leu Gly
65 70 75 80
Pro Gln Glu Pro Thr Gly Ser Gln Leu Leu Arg Ser Lys Lys Leu Pro
85 90 95
Arg Val Arg Glu His Arg Gly Pro Leu Thr Gln Leu Arg Gly His Pro
100 105 110
Pro Arg Trp Gln Pro Ile Phe Cys Val Leu Arg Gly Asp Gly Arg Leu
115 120 125
Glu Trp Phe Ser His Lys Glu Glu Tyr Glu Asn Gly Gly His Cys Leu
130 135 140
Gly Ser Thr Ala Leu Thr Gly Tyr Thr Leu Leu Thr Ser Gln Arg Glu
145 150 155 160
Tyr Leu Arg Leu Leu Asp Ala Leu Cys Pro Glu Ser Leu Gly Asp His
165 170 175
Thr Gln Glu Glu Pro Asp Ser Leu Leu Glu Val Pro Val Ser Phe Pro
180 185 190
Leu Phe Leu Gln His Pro Phe Arg Arg His Leu Cys Phe Ser Ala Ala
195 200 205
Thr Arg Glu Ala Gln His Ala Trp Arg Leu Ala Leu Gln Gly Gly Ile
210 215 220
Arg Leu Gln Gly Ile Val Leu Gln Arg Ser Gln Ala Pro Ala Ala Arg
225 230 235 240
Ala Phe Leu Asp Ala Val Arg Leu Tyr Arg Gln His Gln Gly His Phe
245 250 255
Gly Asp Asp Asp Val Thr Leu Gly Ser Asp Ala Glu Val Leu Thr Ala
260 265 270
Val Leu Met Arg Glu Gln Leu Pro Ala Leu Arg Ala Gln Thr Leu Pro
275 280 285
Gly Leu Arg Gly Ala Gly Arg Ala Arg Ala Trp Ala Trp Thr Glu Leu
290 295 300
Leu Asp Ala Val His Ala Ala Val Leu Ala Gly Ala Ser Ala Gly Leu
305 310 315 320
Cys Ala Phe Gln Pro Glu Lys Asp Glu Leu Leu Ala Ser Leu Glu Lys
325 330 335
Thr Ile Arg Pro Asp Val Asp Gln Leu Leu Arg Gln Arg Ala Arg Val
340 345 350
Ala Gly Arg Leu Arg Thr Asp Ile Arg Gly Pro Leu Glu Ser Cys Leu
355 360 365
Arg Arg Glu Val Asp Pro Gln Leu Pro Arg Val Val Gln Thr Leu Leu
370 375 380
Arg Thr Val Glu Ala Ser Leu Glu Ala Val Arg Thr Leu Leu Ala Gln
385 390 395 400
Gly Met Asp Arg Leu Ser His Arg Leu Arg Gln Ser Pro Ser Gly Thr
405 410 415
Arg Leu Arg Arg Glu Val Tyr Ser Phe Gly Glu Met Pro Trp Asp Leu
420 425 430
Ala Leu Met Gln Thr Cys Tyr Arg Glu Ala Glu Arg Ser Arg Gly Arg
435 440 445
Leu Gly Gln Leu Ala Ala Pro Phe Gly Phe Leu Gly Met Gln Ser Leu
450 455 460
Val Phe Gly Ala Gln Asp Leu Ala Gln Gln Leu Met Ala Asp Ala Val
465 470 475 480
Ala Thr Phe Leu Gln Leu Ala Asp Gln Cys Leu Thr Thr Ala Leu Asn
485 490 495
Cys Asp Gln Ala Ala Gln Arg Leu Glu Arg Val Arg Gly Arg Val Leu
500 505 510
Lys Lys Phe Lys Ser Asp Ser Gly Leu Ala Gln Arg Arg Phe Ile Arg
515 520 525
Gly Trp Gly Leu Cys Ile Phe Leu Pro Phe Val Leu Ser Gln Leu Glu
530 535 540
Pro Gly Cys Lys Lys Glu Leu Pro Glu Phe Glu Gly Asp Val Leu Ala
545 550 555 560
Val Gly Ser Gln Ala Leu Thr Thr Glu Gly Ile Tyr Glu Asp Val Ile
565 570 575
Arg Gly Cys Leu Leu Gln Arg Ile Asp Gln Glu Leu Lys Lys Thr Leu
580 585 590
Gly Ala Asn Asp Val Ser Cys Thr Leu Asp Gly Cys Leu Glu Val Pro
595 600 605
Trp Glu Gln Glu Gly Ala Ala Pro Asn Leu Asn Leu Val Ser Ser Phe
610 615 620
Leu Ala Gly Arg Gln Ala Phe Thr Asp Phe Leu Cys Leu Pro Ala Lys
625 630 635 640
Ser Ser Ala Asn Trp Ile Leu Ala Ala Ser Leu Leu Ser Cys Ser Cys
645 650 655
Phe Arg Ser Gly Phe His Arg Asp Ser Arg Val Phe Leu Val Gln Leu
660 665 670
Ala Glu Gly Leu Ser His Ser Leu Glu Thr Val Ser Ser His Ser Val
675 680 685
Trp Ser Phe Arg Pro Thr Pro Arg Gln
690 695
<210> 64
<211> 760
<212> PRT
<213> 智人
<400> 64
Met Lys Thr Trp Val Lys Ile Val Phe Gly Val Ala Thr Ser Ala Val
1 5 10 15
Leu Ala Leu Leu Val Met Cys Ile Val Leu Arg Pro Ser Arg Val His
20 25 30
Asn Ser Glu Glu Asn Thr Met Arg Ala Leu Thr Leu Lys Asp Ile Leu
35 40 45
Asn Gly Thr Phe Ser Tyr Lys Thr Phe Phe Pro Asn Trp Ile Ser Gly
50 55 60
Gln Glu Tyr Leu His Gln Ser Ala Asp Asn Asn Ile Val Leu Tyr Asn
65 70 75 80
Ile Glu Thr Gly Gln Ser Tyr Thr Ile Leu Ser Asn Arg Thr Met Lys
85 90 95
Ser Val Asn Ala Ser Asn Tyr Gly Leu Ser Pro Asp Arg Gln Phe Val
100 105 110
Tyr Leu Glu Ser Asp Tyr Ser Lys Leu Trp Arg Tyr Ser Tyr Thr Ala
115 120 125
Thr Tyr Tyr Ile Tyr Asp Leu Ser Asn Gly Glu Phe Val Arg Gly Asn
130 135 140
Glu Leu Pro Arg Pro Ile Gln Tyr Leu Cys Trp Ser Pro Val Gly Ser
145 150 155 160
Lys Leu Ala Tyr Val Tyr Gln Asn Asn Ile Tyr Leu Lys Gln Arg Pro
165 170 175
Gly Asp Pro Pro Phe Gln Ile Thr Phe Asn Gly Arg Glu Asn Lys Ile
180 185 190
Phe Asn Gly Ile Pro Asp Trp Val Tyr Glu Glu Glu Met Leu Ala Thr
195 200 205
Lys Tyr Ala Leu Trp Trp Ser Pro Asn Gly Lys Phe Leu Ala Tyr Ala
210 215 220
Glu Phe Asn Asp Thr Asp Ile Pro Val Ile Ala Tyr Ser Tyr Tyr Gly
225 230 235 240
Asp Glu Gln Tyr Pro Arg Thr Ile Asn Ile Pro Tyr Pro Lys Ala Gly
245 250 255
Ala Lys Asn Pro Val Val Arg Ile Phe Ile Ile Asp Thr Thr Tyr Pro
260 265 270
Ala Tyr Val Gly Pro Gln Glu Val Pro Val Pro Ala Met Ile Ala Ser
275 280 285
Ser Asp Tyr Tyr Phe Ser Trp Leu Thr Trp Val Thr Asp Glu Arg Val
290 295 300
Cys Leu Gln Trp Leu Lys Arg Val Gln Asn Val Ser Val Leu Ser Ile
305 310 315 320
Cys Asp Phe Arg Glu Asp Trp Gln Thr Trp Asp Cys Pro Lys Thr Gln
325 330 335
Glu His Ile Glu Glu Ser Arg Thr Gly Trp Ala Gly Gly Phe Phe Val
340 345 350
Ser Thr Pro Val Phe Ser Tyr Asp Ala Ile Ser Tyr Tyr Lys Ile Phe
355 360 365
Ser Asp Lys Asp Gly Tyr Lys His Ile His Tyr Ile Lys Asp Thr Val
370 375 380
Glu Asn Ala Ile Gln Ile Thr Ser Gly Lys Trp Glu Ala Ile Asn Ile
385 390 395 400
Phe Arg Val Thr Gln Asp Ser Leu Phe Tyr Ser Ser Asn Glu Phe Glu
405 410 415
Glu Tyr Pro Gly Arg Arg Asn Ile Tyr Arg Ile Ser Ile Gly Ser Tyr
420 425 430
Pro Pro Ser Lys Lys Cys Val Thr Cys His Leu Arg Lys Glu Arg Cys
435 440 445
Gln Tyr Tyr Thr Ala Ser Phe Ser Asp Tyr Ala Lys Tyr Tyr Ala Leu
450 455 460
Val Cys Tyr Gly Pro Gly Ile Pro Ile Ser Thr Leu His Asp Gly Arg
465 470 475 480
Thr Asp Gln Glu Ile Lys Ile Leu Glu Glu Asn Lys Glu Leu Glu Asn
485 490 495
Ala Leu Lys Asn Ile Gln Leu Pro Lys Glu Glu Ile Lys Lys Leu Glu
500 505 510
Val Asp Glu Ile Thr Leu Trp Tyr Lys Met Ile Leu Pro Pro Gln Phe
515 520 525
Asp Arg Ser Lys Lys Tyr Pro Leu Leu Ile Gln Val Tyr Gly Gly Pro
530 535 540
Cys Ser Gln Ser Val Arg Ser Val Phe Ala Val Asn Trp Ile Ser Tyr
545 550 555 560
Leu Ala Ser Lys Glu Gly Met Val Ile Ala Leu Val Asp Gly Arg Gly
565 570 575
Thr Ala Phe Gln Gly Asp Lys Leu Leu Tyr Ala Val Tyr Arg Lys Leu
580 585 590
Gly Val Tyr Glu Val Glu Asp Gln Ile Thr Ala Val Arg Lys Phe Ile
595 600 605
Glu Met Gly Phe Ile Asp Glu Lys Arg Ile Ala Ile Trp Gly Trp Ser
610 615 620
Tyr Gly Gly Tyr Val Ser Ser Leu Ala Leu Ala Ser Gly Thr Gly Leu
625 630 635 640
Phe Lys Cys Gly Ile Ala Val Ala Pro Val Ser Ser Trp Glu Tyr Tyr
645 650 655
Ala Ser Val Tyr Thr Glu Arg Phe Met Gly Leu Pro Thr Lys Asp Asp
660 665 670
Asn Leu Glu His Tyr Lys Asn Ser Thr Val Met Ala Arg Ala Glu Tyr
675 680 685
Phe Arg Asn Val Asp Tyr Leu Leu Ile His Gly Thr Ala Asp Asp Asn
690 695 700
Val His Phe Gln Asn Ser Ala Gln Ile Ala Lys Ala Leu Val Asn Ala
705 710 715 720
Gln Val Asp Phe Gln Ala Met Trp Tyr Ser Asp Gln Asn His Gly Leu
725 730 735
Ser Gly Leu Ser Thr Asn His Leu Tyr Thr His Met Thr His Phe Leu
740 745 750
Lys Gln Cys Phe Ser Leu Ser Asp
755 760
<210> 65
<211> 387
<212> PRT
<213> 智人
<400> 65
Met Ala Gly Ser Glu Pro Arg Ser Gly Thr Asn Ser Pro Pro Pro Pro
1 5 10 15
Phe Ser Asp Trp Gly Arg Leu Glu Ala Ala Ile Leu Ser Gly Trp Lys
20 25 30
Thr Phe Trp Gln Ser Val Ser Lys Glu Arg Val Ala Arg Thr Thr Ser
35 40 45
Arg Glu Glu Val Asp Glu Ala Ala Ser Thr Leu Thr Arg Leu Pro Ile
50 55 60
Asp Val Gln Leu Tyr Ile Leu Ser Phe Leu Ser Pro His Asp Leu Cys
65 70 75 80
Gln Leu Gly Ser Thr Asn His Tyr Trp Asn Glu Thr Val Arg Asp Pro
85 90 95
Ile Leu Trp Arg Tyr Phe Leu Leu Arg Asp Leu Pro Ser Trp Ser Ser
100 105 110
Val Asp Trp Lys Ser Leu Pro Asp Leu Glu Ile Leu Lys Lys Pro Ile
115 120 125
Ser Glu Val Thr Asp Gly Ala Phe Phe Asp Tyr Met Ala Val Tyr Arg
130 135 140
Met Cys Cys Pro Tyr Thr Arg Arg Ala Ser Lys Ser Ser Arg Pro Met
145 150 155 160
Tyr Gly Ala Val Thr Ser Phe Leu His Ser Leu Ile Ile Gln Asn Glu
165 170 175
Pro Arg Phe Ala Met Phe Gly Pro Gly Leu Glu Glu Leu Asn Thr Ser
180 185 190
Leu Val Leu Ser Leu Met Ser Ser Glu Glu Leu Cys Pro Thr Ala Gly
195 200 205
Leu Pro Gln Arg Gln Ile Asp Gly Ile Gly Ser Gly Val Asn Phe Gln
210 215 220
Leu Asn Asn Gln His Lys Phe Asn Ile Leu Ile Leu Tyr Ser Thr Thr
225 230 235 240
Arg Lys Glu Arg Asp Arg Ala Arg Glu Glu His Thr Ser Ala Val Asn
245 250 255
Lys Met Phe Ser Arg His Asn Glu Gly Asp Asp Gln Gln Gly Ser Arg
260 265 270
Tyr Ser Val Ile Pro Gln Ile Gln Lys Val Cys Glu Val Val Asp Gly
275 280 285
Phe Ile Tyr Val Ala Asn Ala Glu Ala His Lys Arg His Glu Trp Gln
290 295 300
Asp Glu Phe Ser His Ile Met Ala Met Thr Asp Pro Ala Phe Gly Ser
305 310 315 320
Ser Gly Arg Pro Leu Leu Val Leu Ser Cys Ile Ser Gln Gly Asp Val
325 330 335
Lys Arg Met Pro Cys Phe Tyr Leu Ala His Glu Leu His Leu Asn Leu
340 345 350
Leu Asn His Pro Trp Leu Val Gln Asp Thr Glu Ala Glu Thr Leu Thr
355 360 365
Gly Phe Leu Asn Gly Ile Glu Trp Ile Leu Glu Glu Val Glu Ser Lys
370 375 380
Arg Ala Arg
385
<210> 66
<211> 491
<212> PRT
<213> 智人
<400> 66
Met Lys Arg Met Val Ser Trp Ser Phe His Lys Leu Lys Thr Met Lys
1 5 10 15
His Leu Leu Leu Leu Leu Leu Cys Val Phe Leu Val Lys Ser Gln Gly
20 25 30
Val Asn Asp Asn Glu Glu Gly Phe Phe Ser Ala Arg Gly His Arg Pro
35 40 45
Leu Asp Lys Lys Arg Glu Glu Ala Pro Ser Leu Arg Pro Ala Pro Pro
50 55 60
Pro Ile Ser Gly Gly Gly Tyr Arg Ala Arg Pro Ala Lys Ala Ala Ala
65 70 75 80
Thr Gln Lys Lys Val Glu Arg Lys Ala Pro Asp Ala Gly Gly Cys Leu
85 90 95
His Ala Asp Pro Asp Leu Gly Val Leu Cys Pro Thr Gly Cys Gln Leu
100 105 110
Gln Glu Ala Leu Leu Gln Gln Glu Arg Pro Ile Arg Asn Ser Val Asp
115 120 125
Glu Leu Asn Asn Asn Val Glu Ala Val Ser Gln Thr Ser Ser Ser Ser
130 135 140
Phe Gln Tyr Met Tyr Leu Leu Lys Asp Leu Trp Gln Lys Arg Gln Lys
145 150 155 160
Gln Val Lys Asp Asn Glu Asn Val Val Asn Glu Tyr Ser Ser Glu Leu
165 170 175
Glu Lys His Gln Leu Tyr Ile Asp Glu Thr Val Asn Ser Asn Ile Pro
180 185 190
Thr Asn Leu Arg Val Leu Arg Ser Ile Leu Glu Asn Leu Arg Ser Lys
195 200 205
Ile Gln Lys Leu Glu Ser Asp Val Ser Ala Gln Met Glu Tyr Cys Arg
210 215 220
Thr Pro Cys Thr Val Ser Cys Asn Ile Pro Val Val Ser Gly Lys Glu
225 230 235 240
Cys Glu Glu Ile Ile Arg Lys Gly Gly Glu Thr Ser Glu Met Tyr Leu
245 250 255
Ile Gln Pro Asp Ser Ser Val Lys Pro Tyr Arg Val Tyr Cys Asp Met
260 265 270
Asn Thr Glu Asn Gly Gly Trp Thr Val Ile Gln Asn Arg Gln Asp Gly
275 280 285
Ser Val Asp Phe Gly Arg Lys Trp Asp Pro Tyr Lys Gln Gly Phe Gly
290 295 300
Asn Val Ala Thr Asn Thr Asp Gly Lys Asn Tyr Cys Gly Leu Pro Gly
305 310 315 320
Glu Tyr Trp Leu Gly Asn Asp Lys Ile Ser Gln Leu Thr Arg Met Gly
325 330 335
Pro Thr Glu Leu Leu Ile Glu Met Glu Asp Trp Lys Gly Asp Lys Val
340 345 350
Lys Ala His Tyr Gly Gly Phe Thr Val Gln Asn Glu Ala Asn Lys Tyr
355 360 365
Gln Ile Ser Val Asn Lys Tyr Arg Gly Thr Ala Gly Asn Ala Leu Met
370 375 380
Asp Gly Ala Ser Gln Leu Met Gly Glu Asn Arg Thr Met Thr Ile His
385 390 395 400
Asn Gly Met Phe Phe Ser Thr Tyr Asp Arg Asp Asn Asp Gly Trp Leu
405 410 415
Thr Ser Asp Pro Arg Lys Gln Cys Ser Lys Glu Asp Gly Gly Gly Trp
420 425 430
Trp Tyr Asn Arg Cys His Ala Ala Asn Pro Asn Gly Arg Tyr Tyr Trp
435 440 445
Gly Gly Gln Tyr Thr Trp Asp Met Ala Lys His Gly Thr Asp Asp Gly
450 455 460
Val Val Trp Met Asn Trp Lys Gly Ser Trp Tyr Ser Met Arg Lys Met
465 470 475 480
Ser Met Lys Ile Arg Pro Phe Phe Pro Gln Gln
485 490
<210> 67
<211> 453
<212> PRT
<213> 智人
<400> 67
Met Ser Trp Ser Leu His Pro Arg Asn Leu Ile Leu Tyr Phe Tyr Ala
1 5 10 15
Leu Leu Phe Leu Ser Ser Thr Cys Val Ala Tyr Val Ala Thr Arg Asp
20 25 30
Asn Cys Cys Ile Leu Asp Glu Arg Phe Gly Ser Tyr Cys Pro Thr Thr
35 40 45
Cys Gly Ile Ala Asp Phe Leu Ser Thr Tyr Gln Thr Lys Val Asp Lys
50 55 60
Asp Leu Gln Ser Leu Glu Asp Ile Leu His Gln Val Glu Asn Lys Thr
65 70 75 80
Ser Glu Val Lys Gln Leu Ile Lys Ala Ile Gln Leu Thr Tyr Asn Pro
85 90 95
Asp Glu Ser Ser Lys Pro Asn Met Ile Asp Ala Ala Thr Leu Lys Ser
100 105 110
Arg Lys Met Leu Glu Glu Ile Met Lys Tyr Glu Ala Ser Ile Leu Thr
115 120 125
His Asp Ser Ser Ile Arg Tyr Leu Gln Glu Ile Tyr Asn Ser Asn Asn
130 135 140
Gln Lys Ile Val Asn Leu Lys Glu Lys Val Ala Gln Leu Glu Ala Gln
145 150 155 160
Cys Gln Glu Pro Cys Lys Asp Thr Val Gln Ile His Asp Ile Thr Gly
165 170 175
Lys Asp Cys Gln Asp Ile Ala Asn Lys Gly Ala Lys Gln Ser Gly Leu
180 185 190
Tyr Phe Ile Lys Pro Leu Lys Ala Asn Gln Gln Phe Leu Val Tyr Cys
195 200 205
Glu Ile Asp Gly Ser Gly Asn Gly Trp Thr Val Phe Gln Lys Arg Leu
210 215 220
Asp Gly Ser Val Asp Phe Lys Lys Asn Trp Ile Gln Tyr Lys Glu Gly
225 230 235 240
Phe Gly His Leu Ser Pro Thr Gly Thr Thr Glu Phe Trp Leu Gly Asn
245 250 255
Glu Lys Ile His Leu Ile Ser Thr Gln Ser Ala Ile Pro Tyr Ala Leu
260 265 270
Arg Val Glu Leu Glu Asp Trp Asn Gly Arg Thr Ser Thr Ala Asp Tyr
275 280 285
Ala Met Phe Lys Val Gly Pro Glu Ala Asp Lys Tyr Arg Leu Thr Tyr
290 295 300
Ala Tyr Phe Ala Gly Gly Asp Ala Gly Asp Ala Phe Asp Gly Phe Asp
305 310 315 320
Phe Gly Asp Asp Pro Ser Asp Lys Phe Phe Thr Ser His Asn Gly Met
325 330 335
Gln Phe Ser Thr Trp Asp Asn Asp Asn Asp Lys Phe Glu Gly Asn Cys
340 345 350
Ala Glu Gln Asp Gly Ser Gly Trp Trp Met Asn Lys Cys His Ala Gly
355 360 365
His Leu Asn Gly Val Tyr Tyr Gln Gly Gly Thr Tyr Ser Lys Ala Ser
370 375 380
Thr Pro Asn Gly Tyr Asp Asn Gly Ile Ile Trp Ala Thr Trp Lys Thr
385 390 395 400
Arg Trp Tyr Ser Met Lys Lys Thr Thr Met Lys Ile Ile Pro Phe Asn
405 410 415
Arg Leu Thr Ile Gly Glu Gly Gln Gln His His Leu Gly Gly Ala Lys
420 425 430
Gln Val Arg Pro Glu His Pro Ala Glu Thr Glu Tyr Asp Ser Leu Tyr
435 440 445
Pro Glu Asp Asp Leu
450
<210> 68
<211> 323
<212> PRT
<213> 智人
<400> 68
Met Ala Glu Lys Phe Asp Cys His Tyr Cys Arg Asp Pro Leu Gln Gly
1 5 10 15
Lys Lys Tyr Val Gln Lys Asp Gly His His Cys Cys Leu Lys Cys Phe
20 25 30
Asp Lys Phe Cys Ala Asn Thr Cys Val Glu Cys Arg Lys Pro Ile Gly
35 40 45
Ala Asp Ser Lys Glu Val His Tyr Lys Asn Arg Phe Trp His Asp Thr
50 55 60
Cys Phe Arg Cys Ala Lys Cys Leu His Pro Leu Ala Asn Glu Thr Phe
65 70 75 80
Val Ala Lys Asp Asn Lys Ile Leu Cys Asn Lys Cys Thr Thr Arg Glu
85 90 95
Asp Ser Pro Lys Cys Lys Gly Cys Phe Lys Ala Ile Val Ala Gly Asp
100 105 110
Gln Asn Val Glu Tyr Lys Gly Thr Val Trp His Lys Asp Cys Phe Thr
115 120 125
Cys Ser Asn Cys Lys Gln Val Ile Gly Thr Gly Ser Phe Phe Pro Lys
130 135 140
Gly Glu Asp Phe Tyr Cys Val Thr Cys His Glu Thr Lys Phe Ala Lys
145 150 155 160
His Cys Val Lys Cys Asn Lys Ala Ile Thr Ser Gly Gly Ile Thr Tyr
165 170 175
Gln Asp Gln Pro Trp His Ala Asp Cys Phe Val Cys Val Thr Cys Ser
180 185 190
Lys Lys Leu Ala Gly Gln Arg Phe Thr Ala Val Glu Asp Gln Tyr Tyr
195 200 205
Cys Val Asp Cys Tyr Lys Asn Phe Val Ala Lys Lys Cys Ala Gly Cys
210 215 220
Lys Asn Pro Ile Thr Gly Lys Arg Thr Val Ser Arg Val Ser His Pro
225 230 235 240
Val Ser Lys Ala Arg Lys Pro Pro Val Cys His Gly Lys Arg Leu Pro
245 250 255
Leu Thr Leu Phe Pro Ser Ala Asn Leu Arg Gly Arg His Pro Gly Gly
260 265 270
Glu Arg Thr Cys Pro Ser Trp Val Val Val Leu Tyr Arg Lys Asn Arg
275 280 285
Ser Leu Ala Ala Pro Arg Gly Pro Gly Leu Val Lys Ala Pro Val Trp
290 295 300
Trp Pro Met Lys Asp Asn Pro Gly Thr Thr Thr Ala Ser Thr Ala Lys
305 310 315 320
Asn Ala Pro
<210> 69
<211> 2647
<212> PRT
<213> 智人
<400> 69
Met Ser Ser Ser His Ser Arg Ala Gly Gln Ser Ala Ala Gly Ala Ala
1 5 10 15
Pro Gly Gly Gly Val Asp Thr Arg Asp Ala Glu Met Pro Ala Thr Glu
20 25 30
Lys Asp Leu Ala Glu Asp Ala Pro Trp Lys Lys Ile Gln Gln Asn Thr
35 40 45
Phe Thr Arg Trp Cys Asn Glu His Leu Lys Cys Val Ser Lys Arg Ile
50 55 60
Ala Asn Leu Gln Thr Asp Leu Ser Asp Gly Leu Arg Leu Ile Ala Leu
65 70 75 80
Leu Glu Val Leu Ser Gln Lys Lys Met His Arg Lys His Asn Gln Arg
85 90 95
Pro Thr Phe Arg Gln Met Gln Leu Glu Asn Val Ser Val Ala Leu Glu
100 105 110
Phe Leu Asp Arg Glu Ser Ile Lys Leu Val Ser Ile Asp Ser Lys Ala
115 120 125
Ile Val Asp Gly Asn Leu Lys Leu Ile Leu Gly Leu Ile Trp Thr Leu
130 135 140
Ile Leu His Tyr Ser Ile Ser Met Pro Met Trp Asp Glu Glu Glu Asp
145 150 155 160
Glu Glu Ala Lys Lys Gln Thr Pro Lys Gln Arg Leu Leu Gly Trp Ile
165 170 175
Gln Asn Lys Leu Pro Gln Leu Pro Ile Thr Asn Phe Ser Arg Asp Trp
180 185 190
Gln Ser Gly Arg Ala Leu Gly Ala Leu Val Asp Ser Cys Ala Pro Gly
195 200 205
Leu Cys Pro Asp Trp Asp Ser Trp Asp Ala Ser Lys Pro Val Thr Asn
210 215 220
Ala Arg Glu Ala Met Gln Gln Ala Asp Asp Trp Leu Gly Ile Pro Gln
225 230 235 240
Val Ile Thr Pro Glu Glu Ile Val Asp Pro Asn Val Asp Glu His Ser
245 250 255
Val Met Thr Tyr Leu Ser Gln Phe Pro Lys Ala Lys Leu Lys Pro Gly
260 265 270
Ala Pro Leu Arg Pro Lys Leu Asn Pro Lys Lys Ala Arg Ala Tyr Gly
275 280 285
Pro Gly Ile Glu Pro Thr Gly Asn Met Val Lys Lys Arg Ala Glu Phe
290 295 300
Thr Val Glu Thr Arg Ser Ala Gly Gln Gly Glu Val Leu Val Tyr Val
305 310 315 320
Glu Asp Pro Ala Gly His Gln Glu Glu Ala Lys Val Thr Ala Asn Asn
325 330 335
Asp Lys Asn Arg Thr Phe Ser Val Trp Tyr Val Pro Glu Val Thr Gly
340 345 350
Thr His Lys Val Thr Val Leu Phe Ala Gly Gln His Ile Ala Lys Ser
355 360 365
Pro Phe Glu Val Tyr Val Asp Lys Ser Gln Gly Asp Ala Ser Lys Val
370 375 380
Thr Ala Gln Gly Pro Gly Leu Glu Pro Ser Gly Asn Ile Ala Asn Lys
385 390 395 400
Thr Thr Tyr Phe Glu Ile Phe Thr Ala Gly Ala Gly Thr Gly Glu Val
405 410 415
Glu Val Val Ile Gln Asp Pro Met Gly Gln Lys Gly Thr Val Glu Pro
420 425 430
Gln Leu Glu Ala Arg Gly Asp Ser Thr Tyr Arg Cys Ser Tyr Gln Pro
435 440 445
Thr Met Glu Gly Val His Thr Val His Val Thr Phe Ala Gly Val Pro
450 455 460
Ile Pro Arg Ser Pro Tyr Thr Val Thr Val Gly Gln Ala Cys Asn Pro
465 470 475 480
Ser Ala Cys Arg Ala Val Gly Arg Gly Leu Gln Pro Lys Gly Val Arg
485 490 495
Val Lys Glu Thr Ala Asp Phe Lys Val Tyr Thr Lys Gly Ala Gly Ser
500 505 510
Gly Glu Leu Lys Val Thr Val Lys Gly Pro Lys Gly Glu Glu Arg Val
515 520 525
Lys Gln Lys Asp Leu Gly Asp Gly Val Tyr Gly Phe Glu Tyr Tyr Pro
530 535 540
Met Val Pro Gly Thr Tyr Ile Val Thr Ile Thr Trp Gly Gly Gln Asn
545 550 555 560
Ile Gly Arg Ser Pro Phe Glu Val Lys Val Gly Thr Glu Cys Gly Asn
565 570 575
Gln Lys Val Arg Ala Trp Gly Pro Gly Leu Glu Gly Gly Val Val Gly
580 585 590
Lys Ser Ala Asp Phe Val Val Glu Ala Ile Gly Asp Asp Val Gly Thr
595 600 605
Leu Gly Phe Ser Val Glu Gly Pro Ser Gln Ala Lys Ile Glu Cys Asp
610 615 620
Asp Lys Gly Asp Gly Ser Cys Asp Val Arg Tyr Trp Pro Gln Glu Ala
625 630 635 640
Gly Glu Tyr Ala Val His Val Leu Cys Asn Ser Glu Asp Ile Arg Leu
645 650 655
Ser Pro Phe Met Ala Asp Ile Arg Asp Ala Pro Gln Asp Phe His Pro
660 665 670
Asp Arg Val Lys Ala Arg Gly Pro Gly Leu Glu Lys Thr Gly Val Ala
675 680 685
Val Asn Lys Pro Ala Glu Phe Thr Val Asp Ala Lys His Gly Gly Lys
690 695 700
Ala Pro Leu Arg Val Gln Val Gln Asp Asn Glu Gly Cys Pro Val Glu
705 710 715 720
Ala Leu Val Lys Asp Asn Gly Asn Gly Thr Tyr Ser Cys Ser Tyr Val
725 730 735
Pro Arg Lys Pro Val Lys His Thr Ala Met Val Ser Trp Gly Gly Val
740 745 750
Ser Ile Pro Asn Ser Pro Phe Arg Val Asn Val Gly Ala Gly Ser His
755 760 765
Pro Asn Lys Val Lys Val Tyr Gly Pro Gly Val Ala Lys Thr Gly Leu
770 775 780
Lys Ala His Glu Pro Thr Tyr Phe Thr Val Asp Cys Ala Glu Ala Gly
785 790 795 800
Gln Gly Asp Val Ser Ile Gly Ile Lys Cys Ala Pro Gly Val Val Gly
805 810 815
Pro Ala Glu Ala Asp Ile Asp Phe Asp Ile Ile Arg Asn Asp Asn Asp
820 825 830
Thr Phe Thr Val Lys Tyr Thr Pro Arg Gly Ala Gly Ser Tyr Thr Ile
835 840 845
Met Val Leu Phe Ala Asp Gln Ala Thr Pro Thr Ser Pro Ile Arg Val
850 855 860
Lys Val Glu Pro Ser His Asp Ala Ser Lys Val Lys Ala Glu Gly Pro
865 870 875 880
Gly Leu Ser Arg Thr Gly Val Glu Leu Gly Lys Pro Thr His Phe Thr
885 890 895
Val Asn Ala Lys Ala Ala Gly Lys Gly Lys Leu Asp Val Gln Phe Ser
900 905 910
Gly Leu Thr Lys Gly Asp Ala Val Arg Asp Val Asp Ile Ile Asp His
915 920 925
His Asp Asn Thr Tyr Thr Val Lys Tyr Thr Pro Val Gln Gln Gly Pro
930 935 940
Val Gly Val Asn Val Thr Tyr Gly Gly Asp Pro Ile Pro Lys Ser Pro
945 950 955 960
Phe Ser Val Ala Val Ser Pro Ser Leu Asp Leu Ser Lys Ile Lys Val
965 970 975
Ser Gly Leu Gly Glu Lys Val Asp Val Gly Lys Asp Gln Glu Phe Thr
980 985 990
Val Lys Ser Lys Gly Ala Gly Gly Gln Gly Lys Val Ala Ser Lys Ile
995 1000 1005
Val Gly Pro Ser Gly Ala Ala Val Pro Cys Lys Val Glu Pro Gly
1010 1015 1020
Leu Gly Ala Asp Asn Ser Val Val Arg Phe Leu Pro Arg Glu Glu
1025 1030 1035
Gly Pro Tyr Glu Val Glu Val Thr Tyr Asp Gly Val Pro Val Pro
1040 1045 1050
Gly Ser Pro Phe Pro Leu Glu Ala Val Ala Pro Thr Lys Pro Ser
1055 1060 1065
Lys Val Lys Ala Phe Gly Pro Gly Leu Gln Gly Gly Ser Ala Gly
1070 1075 1080
Ser Pro Ala Arg Phe Thr Ile Asp Thr Lys Gly Ala Gly Thr Gly
1085 1090 1095
Gly Leu Gly Leu Thr Val Glu Gly Pro Cys Glu Ala Gln Leu Glu
1100 1105 1110
Cys Leu Asp Asn Gly Asp Gly Thr Cys Ser Val Ser Tyr Val Pro
1115 1120 1125
Thr Glu Pro Gly Asp Tyr Asn Ile Asn Ile Leu Phe Ala Asp Thr
1130 1135 1140
His Ile Pro Gly Ser Pro Phe Lys Ala His Val Val Pro Cys Phe
1145 1150 1155
Asp Ala Ser Lys Val Lys Cys Ser Gly Pro Gly Leu Glu Arg Ala
1160 1165 1170
Thr Ala Gly Glu Val Gly Gln Phe Gln Val Asp Cys Ser Ser Ala
1175 1180 1185
Gly Ser Ala Glu Leu Thr Ile Glu Ile Cys Ser Glu Ala Gly Leu
1190 1195 1200
Pro Ala Glu Val Tyr Ile Gln Asp His Gly Asp Gly Thr His Thr
1205 1210 1215
Ile Thr Tyr Ile Pro Leu Cys Pro Gly Ala Tyr Thr Val Thr Ile
1220 1225 1230
Lys Tyr Gly Gly Gln Pro Val Pro Asn Phe Pro Ser Lys Leu Gln
1235 1240 1245
Val Glu Pro Ala Val Asp Thr Ser Gly Val Gln Cys Tyr Gly Pro
1250 1255 1260
Gly Ile Glu Gly Gln Gly Val Phe Arg Glu Ala Thr Thr Glu Phe
1265 1270 1275
Ser Val Asp Ala Arg Ala Leu Thr Gln Thr Gly Gly Pro His Val
1280 1285 1290
Lys Ala Arg Val Ala Asn Pro Ser Gly Asn Leu Thr Glu Thr Tyr
1295 1300 1305
Val Gln Asp Arg Gly Asp Gly Met Tyr Lys Val Glu Tyr Thr Pro
1310 1315 1320
Tyr Glu Glu Gly Leu His Ser Val Asp Val Thr Tyr Asp Gly Ser
1325 1330 1335
Pro Val Pro Ser Ser Pro Phe Gln Val Pro Val Thr Glu Gly Cys
1340 1345 1350
Asp Pro Ser Arg Val Arg Val His Gly Pro Gly Ile Gln Ser Gly
1355 1360 1365
Thr Thr Asn Lys Pro Asn Lys Phe Thr Val Glu Thr Arg Gly Ala
1370 1375 1380
Gly Thr Gly Gly Leu Gly Leu Ala Val Glu Gly Pro Ser Glu Ala
1385 1390 1395
Lys Met Ser Cys Met Asp Asn Lys Asp Gly Ser Cys Ser Val Glu
1400 1405 1410
Tyr Ile Pro Tyr Glu Ala Gly Thr Tyr Ser Leu Asn Val Thr Tyr
1415 1420 1425
Gly Gly His Gln Val Pro Gly Ser Pro Phe Lys Val Pro Val His
1430 1435 1440
Asp Val Thr Asp Ala Ser Lys Val Lys Cys Ser Gly Pro Gly Leu
1445 1450 1455
Ser Pro Gly Met Val Arg Ala Asn Leu Pro Gln Ser Phe Gln Val
1460 1465 1470
Asp Thr Ser Lys Ala Gly Val Ala Pro Leu Gln Val Lys Val Gln
1475 1480 1485
Gly Pro Lys Gly Leu Val Glu Pro Val Asp Val Val Asp Asn Ala
1490 1495 1500
Asp Gly Thr Gln Thr Val Asn Tyr Val Pro Ser Arg Glu Gly Pro
1505 1510 1515
Tyr Ser Ile Ser Val Leu Tyr Gly Asp Glu Glu Val Pro Arg Ser
1520 1525 1530
Pro Phe Lys Val Lys Val Leu Pro Thr His Asp Ala Ser Lys Val
1535 1540 1545
Lys Ala Ser Gly Pro Gly Leu Asn Thr Thr Gly Val Pro Ala Ser
1550 1555 1560
Leu Pro Val Glu Phe Thr Ile Asp Ala Lys Asp Ala Gly Glu Gly
1565 1570 1575
Leu Leu Ala Val Gln Ile Thr Asp Pro Glu Gly Lys Pro Lys Lys
1580 1585 1590
Thr His Ile Gln Asp Asn His Asp Gly Thr Tyr Thr Val Ala Tyr
1595 1600 1605
Val Pro Asp Val Thr Gly Arg Tyr Thr Ile Leu Ile Lys Tyr Gly
1610 1615 1620
Gly Asp Glu Ile Pro Phe Ser Pro Tyr Arg Val Arg Ala Val Pro
1625 1630 1635
Thr Gly Asp Ala Ser Lys Cys Thr Val Thr Val Ser Ile Gly Gly
1640 1645 1650
His Gly Leu Gly Ala Gly Ile Gly Pro Thr Ile Gln Ile Gly Glu
1655 1660 1665
Glu Thr Val Ile Thr Val Asp Thr Lys Ala Ala Gly Lys Gly Lys
1670 1675 1680
Val Thr Cys Thr Val Cys Thr Pro Asp Gly Ser Glu Val Asp Val
1685 1690 1695
Asp Val Val Glu Asn Glu Asp Gly Thr Phe Asp Ile Phe Tyr Thr
1700 1705 1710
Ala Pro Gln Pro Gly Lys Tyr Val Ile Cys Val Arg Phe Gly Gly
1715 1720 1725
Glu His Val Pro Asn Ser Pro Phe Gln Val Thr Ala Leu Ala Gly
1730 1735 1740
Asp Gln Pro Ser Val Gln Pro Pro Leu Arg Ser Gln Gln Leu Ala
1745 1750 1755
Pro Gln Tyr Thr Tyr Ala Gln Gly Gly Gln Gln Thr Trp Ala Pro
1760 1765 1770
Glu Arg Pro Leu Val Gly Val Asn Gly Leu Asp Val Thr Ser Leu
1775 1780 1785
Arg Pro Phe Asp Leu Val Ile Pro Phe Thr Ile Lys Lys Gly Glu
1790 1795 1800
Ile Thr Gly Glu Val Arg Met Pro Ser Gly Lys Val Ala Gln Pro
1805 1810 1815
Thr Ile Thr Asp Asn Lys Asp Gly Thr Val Thr Val Arg Tyr Ala
1820 1825 1830
Pro Ser Glu Ala Gly Leu His Glu Met Asp Ile Arg Tyr Asp Asn
1835 1840 1845
Met His Ile Pro Gly Ser Pro Leu Gln Phe Tyr Val Asp Tyr Val
1850 1855 1860
Asn Cys Gly His Val Thr Ala Tyr Gly Pro Gly Leu Thr His Gly
1865 1870 1875
Val Val Asn Lys Pro Ala Thr Phe Thr Val Asn Thr Lys Asp Ala
1880 1885 1890
Gly Glu Gly Gly Leu Ser Leu Ala Ile Glu Gly Pro Ser Lys Ala
1895 1900 1905
Glu Ile Ser Cys Thr Asp Asn Gln Asp Gly Thr Cys Ser Val Ser
1910 1915 1920
Tyr Leu Pro Val Leu Pro Gly Asp Tyr Ser Ile Leu Val Lys Tyr
1925 1930 1935
Asn Glu Gln His Val Pro Gly Ser Pro Phe Thr Ala Arg Val Thr
1940 1945 1950
Gly Asp Asp Ser Met Arg Met Ser His Leu Lys Val Gly Ser Ala
1955 1960 1965
Ala Asp Ile Pro Ile Asn Ile Ser Glu Thr Asp Leu Ser Leu Leu
1970 1975 1980
Thr Ala Thr Val Val Pro Pro Ser Gly Arg Glu Glu Pro Cys Leu
1985 1990 1995
Leu Lys Arg Leu Arg Asn Gly His Val Gly Ile Ser Phe Val Pro
2000 2005 2010
Lys Glu Thr Gly Glu His Leu Val His Val Lys Lys Asn Gly Gln
2015 2020 2025
His Val Ala Ser Ser Pro Ile Pro Val Val Ile Ser Gln Ser Glu
2030 2035 2040
Ile Gly Asp Ala Ser Arg Val Arg Val Ser Gly Gln Gly Leu His
2045 2050 2055
Glu Gly His Thr Phe Glu Pro Ala Glu Phe Ile Ile Asp Thr Arg
2060 2065 2070
Asp Ala Gly Tyr Gly Gly Leu Ser Leu Ser Ile Glu Gly Pro Ser
2075 2080 2085
Lys Val Asp Ile Asn Thr Glu Asp Leu Glu Asp Gly Thr Cys Arg
2090 2095 2100
Val Thr Tyr Cys Pro Thr Glu Pro Gly Asn Tyr Ile Ile Asn Ile
2105 2110 2115
Lys Phe Ala Asp Gln His Val Pro Gly Ser Pro Phe Ser Val Lys
2120 2125 2130
Val Thr Gly Glu Gly Arg Val Lys Glu Ser Ile Thr Arg Arg Arg
2135 2140 2145
Arg Ala Pro Ser Val Ala Asn Val Gly Ser His Cys Asp Leu Ser
2150 2155 2160
Leu Lys Ile Pro Glu Ile Ser Ile Gln Asp Met Thr Ala Gln Val
2165 2170 2175
Thr Ser Pro Ser Gly Lys Thr His Glu Ala Glu Ile Val Glu Gly
2180 2185 2190
Glu Asn His Thr Tyr Cys Ile Arg Phe Val Pro Ala Glu Met Gly
2195 2200 2205
Thr His Thr Val Ser Val Lys Tyr Lys Gly Gln His Val Pro Gly
2210 2215 2220
Ser Pro Phe Gln Phe Thr Val Gly Pro Leu Gly Glu Gly Gly Ala
2225 2230 2235
His Lys Val Arg Ala Gly Gly Pro Gly Leu Glu Arg Ala Glu Ala
2240 2245 2250
Gly Val Pro Ala Glu Phe Ser Ile Trp Thr Arg Glu Ala Gly Ala
2255 2260 2265
Gly Gly Leu Ala Ile Ala Val Glu Gly Pro Ser Lys Ala Glu Ile
2270 2275 2280
Ser Phe Glu Asp Arg Lys Asp Gly Ser Cys Gly Val Ala Tyr Val
2285 2290 2295
Val Gln Glu Pro Gly Asp Tyr Glu Val Ser Val Lys Phe Asn Glu
2300 2305 2310
Glu His Ile Pro Asp Ser Pro Phe Val Val Pro Val Ala Ser Pro
2315 2320 2325
Ser Gly Asp Ala Arg Arg Leu Thr Val Ser Ser Leu Gln Glu Ser
2330 2335 2340
Gly Leu Lys Val Asn Gln Pro Ala Ser Phe Ala Val Ser Leu Asn
2345 2350 2355
Gly Ala Lys Gly Ala Ile Asp Ala Lys Val His Ser Pro Ser Gly
2360 2365 2370
Ala Leu Glu Glu Cys Tyr Val Thr Glu Ile Asp Gln Asp Lys Tyr
2375 2380 2385
Ala Val Arg Phe Ile Pro Arg Glu Asn Gly Val Tyr Leu Ile Asp
2390 2395 2400
Val Lys Phe Asn Gly Thr His Ile Pro Gly Ser Pro Phe Lys Ile
2405 2410 2415
Arg Val Gly Glu Pro Gly His Gly Gly Asp Pro Gly Leu Val Ser
2420 2425 2430
Ala Tyr Gly Ala Gly Leu Glu Gly Gly Val Thr Gly Asn Pro Ala
2435 2440 2445
Glu Phe Val Val Asn Thr Ser Asn Ala Gly Ala Gly Ala Leu Ser
2450 2455 2460
Val Thr Ile Asp Gly Pro Ser Lys Val Lys Met Asp Cys Gln Glu
2465 2470 2475
Cys Pro Glu Gly Tyr Arg Val Thr Tyr Thr Pro Met Ala Pro Gly
2480 2485 2490
Ser Tyr Leu Ile Ser Ile Lys Tyr Gly Gly Pro Tyr His Ile Gly
2495 2500 2505
Gly Ser Pro Phe Lys Ala Lys Val Thr Gly Pro Arg Leu Val Ser
2510 2515 2520
Asn His Ser Leu His Glu Thr Ser Ser Val Phe Val Asp Ser Leu
2525 2530 2535
Thr Lys Ala Thr Cys Ala Pro Gln His Gly Ala Pro Gly Pro Gly
2540 2545 2550
Pro Ala Asp Ala Ser Lys Val Val Ala Lys Gly Leu Gly Leu Ser
2555 2560 2565
Lys Ala Tyr Val Gly Gln Lys Ser Ser Phe Thr Val Asp Cys Ser
2570 2575 2580
Lys Ala Gly Asn Asn Met Leu Leu Val Gly Val His Gly Pro Arg
2585 2590 2595
Thr Pro Cys Glu Glu Ile Leu Val Lys His Val Gly Ser Arg Leu
2600 2605 2610
Tyr Ser Val Ser Tyr Leu Leu Lys Asp Lys Gly Glu Tyr Thr Leu
2615 2620 2625
Val Val Lys Trp Gly Asp Glu His Ile Pro Gly Ser Pro Tyr Arg
2630 2635 2640
Val Val Val Pro
2645
<210> 70
<211> 597
<212> PRT
<213> 智人
<400> 70
Met Phe Ala Ser Cys His Cys Val Pro Arg Gly Arg Arg Thr Met Lys
1 5 10 15
Met Ile His Phe Arg Ser Ser Ser Val Lys Ser Leu Ser Gln Glu Met
20 25 30
Arg Cys Thr Ile Arg Leu Leu Asp Asp Ser Glu Ile Ser Cys His Ile
35 40 45
Gln Arg Glu Thr Lys Gly Gln Phe Leu Ile Asp His Ile Cys Asn Tyr
50 55 60
Tyr Ser Leu Leu Glu Lys Asp Tyr Phe Gly Ile Arg Tyr Val Asp Pro
65 70 75 80
Glu Lys Gln Arg His Trp Leu Glu Pro Asn Lys Ser Ile Phe Lys Gln
85 90 95
Met Lys Thr His Pro Pro Tyr Thr Met Cys Phe Arg Val Lys Phe Tyr
100 105 110
Pro His Glu Pro Leu Lys Ile Lys Glu Glu Leu Thr Arg Tyr Leu Leu
115 120 125
Tyr Leu Gln Ile Lys Arg Asp Ile Phe His Gly Arg Leu Leu Cys Ser
130 135 140
Phe Ser Asp Ala Ala Tyr Leu Gly Ala Cys Ile Val Gln Ala Glu Leu
145 150 155 160
Gly Asp Tyr Asp Pro Asp Glu His Pro Glu Asn Tyr Ile Ser Glu Phe
165 170 175
Glu Ile Phe Pro Lys Gln Ser Gln Lys Leu Glu Arg Lys Ile Val Glu
180 185 190
Ile His Lys Asn Glu Leu Arg Gly Gln Ser Pro Pro Val Ala Glu Phe
195 200 205
Asn Leu Leu Leu Lys Ala His Thr Leu Glu Thr Tyr Gly Val Asp Pro
210 215 220
His Pro Cys Lys Asp Ser Thr Gly Thr Thr Thr Phe Leu Gly Phe Thr
225 230 235 240
Ala Ala Gly Phe Val Val Phe Gln Gly Asn Lys Arg Ile His Leu Ile
245 250 255
Lys Trp Pro Asp Val Cys Lys Leu Lys Phe Glu Gly Lys Thr Phe Tyr
260 265 270
Val Ile Gly Thr Gln Lys Glu Lys Lys Ala Met Leu Ala Phe His Thr
275 280 285
Ser Thr Pro Ala Ala Cys Lys His Leu Trp Lys Cys Gly Val Glu Asn
290 295 300
Gln Ala Phe Tyr Lys Tyr Ala Lys Ser Ser Gln Ile Lys Thr Val Ser
305 310 315 320
Ser Ser Lys Ile Phe Phe Lys Gly Ser Arg Phe Arg Tyr Ser Gly Lys
325 330 335
Val Ala Lys Glu Val Val Glu Ala Ser Ser Lys Ile Gln Arg Glu Pro
340 345 350
Pro Glu Val His Arg Ala Asn Ile Thr Gln Ser Arg Ser Ser His Ser
355 360 365
Leu Asn Lys Gln Leu Ile Ile Asn Met Glu Pro Leu Gln Pro Leu Leu
370 375 380
Pro Ser Pro Ser Glu Gln Glu Glu Glu Leu Pro Leu Gly Glu Gly Val
385 390 395 400
Pro Leu Pro Lys Glu Glu Asn Ile Ser Ala Pro Leu Ile Ser Ser Ser
405 410 415
Pro Val Lys Ala Ala Arg Glu Tyr Glu Asp Pro Pro Ser Glu Glu Glu
420 425 430
Asp Lys Ile Lys Glu Glu Pro Leu Thr Ile Ser Glu Leu Val Tyr Asn
435 440 445
Pro Ser Ala Ser Leu Leu Pro Thr Pro Val Asp Asp Asp Glu Ile Asp
450 455 460
Met Leu Phe Asp Cys Pro Ser Arg Leu Glu Leu Glu Arg Glu Asp Thr
465 470 475 480
Asp Ser Phe Glu Asp Leu Glu Ala Asp Glu Asn Ala Phe Leu Ile Ala
485 490 495
Glu Glu Glu Glu Leu Lys Glu Ala Arg Arg Ala Leu Ser Trp Ser Tyr
500 505 510
Asp Ile Leu Thr Gly His Ile Arg Val Asn Pro Leu Val Lys Ser Phe
515 520 525
Ser Arg Leu Leu Val Val Gly Leu Gly Leu Leu Leu Phe Val Phe Pro
530 535 540
Leu Leu Leu Leu Leu Leu Glu Ser Gly Ile Asp Leu Ser Phe Leu Cys
545 550 555 560
Glu Ile Arg Gln Thr Pro Glu Phe Glu Gln Phe His Tyr Glu Tyr Tyr
565 570 575
Cys Pro Leu Lys Glu Trp Val Ala Gly Lys Val His Leu Ile Leu Tyr
580 585 590
Met Leu Gly Cys Ser
595
<210> 71
<211> 183
<212> PRT
<213> 智人
<400> 71
Met Thr Thr Ala Ser Thr Ser Gln Val Arg Gln Asn Tyr His Gln Asp
1 5 10 15
Ser Glu Ala Ala Ile Asn Arg Gln Ile Asn Leu Glu Leu Tyr Ala Ser
20 25 30
Tyr Val Tyr Leu Ser Met Ser Tyr Tyr Phe Asp Arg Asp Asp Val Ala
35 40 45
Leu Lys Asn Phe Ala Lys Tyr Phe Leu His Gln Ser His Glu Glu Arg
50 55 60
Glu His Ala Glu Lys Leu Met Lys Leu Gln Asn Gln Arg Gly Gly Arg
65 70 75 80
Ile Phe Leu Gln Asp Ile Lys Lys Pro Asp Cys Asp Asp Trp Glu Ser
85 90 95
Gly Leu Asn Ala Met Glu Cys Ala Leu His Leu Glu Lys Asn Val Asn
100 105 110
Gln Ser Leu Leu Glu Leu His Lys Leu Ala Thr Asp Lys Asn Asp Pro
115 120 125
His Leu Cys Asp Phe Ile Glu Thr His Tyr Leu Asn Glu Gln Val Lys
130 135 140
Ala Ile Lys Glu Leu Gly Asp His Val Thr Asn Leu Arg Lys Met Gly
145 150 155 160
Ala Pro Glu Ser Gly Leu Ala Glu Tyr Leu Phe Asp Lys His Thr Leu
165 170 175
Gly Asp Ser Asp Asn Glu Ser
180
<210> 72
<211> 175
<212> PRT
<213> 智人
<400> 72
Met Ser Ser Gln Ile Arg Gln Asn Tyr Ser Thr Asp Val Glu Ala Ala
1 5 10 15
Val Asn Ser Leu Val Asn Leu Tyr Leu Gln Ala Ser Tyr Thr Tyr Leu
20 25 30
Ser Leu Gly Phe Tyr Phe Asp Arg Asp Asp Val Ala Leu Glu Gly Val
35 40 45
Ser His Phe Phe Arg Glu Leu Ala Glu Glu Lys Arg Glu Gly Tyr Glu
50 55 60
Arg Leu Leu Lys Met Gln Asn Gln Arg Gly Gly Arg Ala Leu Phe Gln
65 70 75 80
Asp Ile Lys Lys Pro Ala Glu Asp Glu Trp Gly Lys Thr Pro Asp Ala
85 90 95
Met Lys Ala Ala Met Ala Leu Glu Lys Lys Leu Asn Gln Ala Leu Leu
100 105 110
Asp Leu His Ala Leu Gly Ser Ala Arg Thr Asp Pro His Leu Cys Asp
115 120 125
Phe Leu Glu Thr His Phe Leu Asp Glu Glu Val Lys Leu Ile Lys Lys
130 135 140
Met Gly Asp His Leu Thr Asn Leu His Arg Leu Gly Gly Pro Glu Ala
145 150 155 160
Gly Leu Gly Glu Tyr Leu Phe Glu Arg Leu Thr Leu Lys His Asp
165 170 175
<210> 73
<211> 466
<212> PRT
<213> 智人
<400> 73
Met Arg Ala Pro Gly Met Arg Ser Arg Pro Ala Gly Pro Ala Leu Leu
1 5 10 15
Leu Leu Leu Leu Phe Leu Gly Ala Ala Glu Ser Val Arg Arg Ala Gln
20 25 30
Pro Pro Arg Arg Tyr Thr Pro Asp Trp Pro Ser Leu Asp Ser Arg Pro
35 40 45
Leu Pro Ala Trp Phe Asp Glu Ala Lys Phe Gly Val Phe Ile His Trp
50 55 60
Gly Val Phe Ser Val Pro Ala Trp Gly Ser Glu Trp Phe Trp Trp His
65 70 75 80
Trp Gln Gly Glu Gly Arg Pro Gln Tyr Gln Arg Phe Met Arg Asp Asn
85 90 95
Tyr Pro Pro Gly Phe Ser Tyr Ala Asp Phe Gly Pro Gln Phe Thr Ala
100 105 110
Arg Phe Phe His Pro Glu Glu Trp Ala Asp Leu Phe Gln Ala Ala Gly
115 120 125
Ala Lys Tyr Val Val Leu Thr Thr Lys His His Glu Gly Phe Thr Asn
130 135 140
Trp Pro Ser Pro Val Ser Trp Asn Trp Asn Ser Lys Asp Val Gly Pro
145 150 155 160
His Arg Asp Leu Val Gly Glu Leu Gly Thr Ala Leu Arg Lys Arg Asn
165 170 175
Ile Arg Tyr Gly Leu Tyr His Ser Leu Leu Glu Trp Phe His Pro Leu
180 185 190
Tyr Leu Leu Asp Lys Lys Asn Gly Phe Lys Thr Gln His Phe Val Ser
195 200 205
Ala Lys Thr Met Pro Glu Leu Tyr Asp Leu Val Asn Ser Tyr Lys Pro
210 215 220
Asp Leu Ile Trp Ser Asp Gly Glu Trp Glu Cys Pro Asp Thr Tyr Trp
225 230 235 240
Asn Ser Thr Asn Phe Leu Ser Trp Leu Tyr Asn Asp Ser Pro Val Lys
245 250 255
Asp Glu Val Val Val Asn Asp Arg Trp Gly Gln Asn Cys Ser Cys His
260 265 270
His Gly Gly Tyr Tyr Asn Cys Glu Asp Lys Phe Lys Pro Gln Ser Leu
275 280 285
Pro Asp His Lys Trp Glu Met Cys Thr Ser Ile Asp Lys Phe Ser Trp
290 295 300
Gly Tyr Arg Arg Asp Met Ala Leu Ser Asp Val Thr Glu Glu Ser Glu
305 310 315 320
Ile Ile Ser Glu Leu Val Gln Thr Val Ser Leu Gly Gly Asn Tyr Leu
325 330 335
Leu Asn Ile Gly Pro Thr Lys Asp Gly Leu Ile Val Pro Ile Phe Gln
340 345 350
Glu Arg Leu Leu Ala Val Gly Lys Trp Leu Ser Ile Asn Gly Glu Ala
355 360 365
Ile Tyr Ala Ser Lys Pro Trp Arg Val Gln Trp Glu Lys Asn Thr Thr
370 375 380
Ser Val Trp Tyr Thr Ser Lys Gly Ser Ala Val Tyr Ala Ile Phe Leu
385 390 395 400
His Trp Pro Glu Asn Gly Val Leu Asn Leu Glu Ser Pro Ile Thr Thr
405 410 415
Ser Thr Thr Lys Ile Thr Met Leu Gly Ile Gln Gly Asp Leu Lys Trp
420 425 430
Ser Thr Asp Pro Asp Lys Gly Leu Phe Ile Ser Leu Pro Gln Leu Pro
435 440 445
Pro Ser Ala Val Pro Ala Glu Phe Ala Trp Thr Ile Lys Leu Thr Gly
450 455 460
Val Lys
465
<210> 74
<211> 456
<212> PRT
<213> 智人
<400> 74
Met Arg Lys Ser Pro Gly Leu Ser Asp Cys Leu Trp Ala Trp Ile Leu
1 5 10 15
Leu Leu Ser Thr Leu Thr Gly Arg Ser Tyr Gly Gln Pro Ser Leu Gln
20 25 30
Asp Glu Leu Lys Asp Asn Thr Thr Val Phe Thr Arg Ile Leu Asp Arg
35 40 45
Leu Leu Asp Gly Tyr Asp Asn Arg Leu Arg Pro Gly Leu Gly Glu Arg
50 55 60
Val Thr Glu Val Lys Thr Asp Ile Phe Val Thr Ser Phe Gly Pro Val
65 70 75 80
Ser Asp His Asp Met Glu Tyr Thr Ile Asp Val Phe Phe Arg Gln Ser
85 90 95
Trp Lys Asp Glu Arg Leu Lys Phe Lys Gly Pro Met Thr Val Leu Arg
100 105 110
Leu Asn Asn Leu Met Ala Ser Lys Ile Trp Thr Pro Asp Thr Phe Phe
115 120 125
His Asn Gly Lys Lys Ser Val Ala His Asn Met Thr Met Pro Asn Lys
130 135 140
Leu Leu Arg Ile Thr Glu Asp Gly Thr Leu Leu Tyr Thr Met Arg Leu
145 150 155 160
Thr Val Arg Ala Glu Cys Pro Met His Leu Glu Asp Phe Pro Met Asp
165 170 175
Ala His Ala Cys Pro Leu Lys Phe Gly Ser Tyr Ala Tyr Thr Arg Ala
180 185 190
Glu Val Val Tyr Glu Trp Thr Arg Glu Pro Ala Arg Ser Val Val Val
195 200 205
Ala Glu Asp Gly Ser Arg Leu Asn Gln Tyr Asp Leu Leu Gly Gln Thr
210 215 220
Val Asp Ser Gly Ile Val Gln Ser Ser Thr Gly Glu Tyr Val Val Met
225 230 235 240
Thr Thr His Phe His Leu Lys Arg Lys Ile Gly Tyr Phe Val Ile Gln
245 250 255
Thr Tyr Leu Pro Cys Ile Met Thr Val Ile Leu Ser Gln Val Ser Phe
260 265 270
Trp Leu Asn Arg Glu Ser Val Pro Ala Arg Thr Val Phe Gly Val Thr
275 280 285
Thr Val Leu Thr Met Thr Thr Leu Ser Ile Ser Ala Arg Asn Ser Leu
290 295 300
Pro Lys Val Ala Tyr Ala Thr Ala Met Asp Trp Phe Ile Ala Val Cys
305 310 315 320
Tyr Ala Phe Val Phe Ser Ala Leu Ile Glu Phe Ala Thr Val Asn Tyr
325 330 335
Phe Thr Lys Arg Gly Tyr Ala Trp Asp Gly Lys Ser Val Val Pro Glu
340 345 350
Lys Pro Lys Lys Val Lys Asp Pro Leu Ile Lys Lys Asn Asn Thr Tyr
355 360 365
Ala Pro Thr Ala Thr Ser Tyr Thr Pro Asn Leu Ala Arg Gly Asp Pro
370 375 380
Gly Leu Ala Thr Ile Ala Lys Ser Ala Thr Ile Glu Pro Lys Glu Val
385 390 395 400
Lys Pro Glu Thr Lys Pro Pro Glu Pro Lys Lys Thr Phe Asn Ser Val
405 410 415
Ser Lys Ile Asp Arg Leu Ser Arg Ile Ala Phe Pro Leu Leu Phe Gly
420 425 430
Ile Phe Asn Leu Val Tyr Trp Ala Thr Tyr Leu Asn Arg Glu Pro Gln
435 440 445
Leu Lys Ala Pro Thr Pro His Gln
450 455
<210> 75
<211> 335
<212> PRT
<213> 智人
<400> 75
Met Gly Lys Val Lys Val Gly Val Asn Gly Phe Gly Arg Ile Gly Arg
1 5 10 15
Leu Val Thr Arg Ala Ala Phe Asn Ser Gly Lys Val Asp Ile Val Ala
20 25 30
Ile Asn Asp Pro Phe Ile Asp Leu Asn Tyr Met Val Tyr Met Phe Gln
35 40 45
Tyr Asp Ser Thr His Gly Lys Phe His Gly Thr Val Lys Ala Glu Asn
50 55 60
Gly Lys Leu Val Ile Asn Gly Asn Pro Ile Thr Ile Phe Gln Glu Arg
65 70 75 80
Asp Pro Ser Lys Ile Lys Trp Gly Asp Ala Gly Ala Glu Tyr Val Val
85 90 95
Glu Ser Thr Gly Val Phe Thr Thr Met Glu Lys Ala Gly Ala His Leu
100 105 110
Gln Gly Gly Ala Lys Arg Val Ile Ile Ser Ala Pro Ser Ala Asp Ala
115 120 125
Pro Met Phe Val Met Gly Val Asn His Glu Lys Tyr Asp Asn Ser Leu
130 135 140
Lys Ile Ile Ser Asn Ala Ser Cys Thr Thr Asn Cys Leu Ala Pro Leu
145 150 155 160
Ala Lys Val Ile His Asp Asn Phe Gly Ile Val Glu Gly Leu Met Thr
165 170 175
Thr Val His Ala Ile Thr Ala Thr Gln Lys Thr Val Asp Gly Pro Ser
180 185 190
Gly Lys Leu Trp Arg Asp Gly Arg Gly Ala Leu Gln Asn Ile Ile Pro
195 200 205
Ala Ser Thr Gly Ala Ala Lys Ala Val Gly Lys Val Ile Pro Glu Leu
210 215 220
Asn Gly Lys Leu Thr Gly Met Ala Phe Arg Val Pro Thr Ala Asn Val
225 230 235 240
Ser Val Val Asp Leu Thr Cys Arg Leu Glu Lys Pro Ala Lys Tyr Asp
245 250 255
Asp Ile Lys Lys Val Val Lys Gln Ala Ser Glu Gly Pro Leu Lys Gly
260 265 270
Ile Leu Gly Tyr Thr Glu His Gln Val Val Ser Ser Asp Phe Asn Ser
275 280 285
Asp Thr His Ser Ser Thr Phe Asp Ala Gly Ala Gly Ile Ala Leu Asn
290 295 300
Asp His Phe Val Lys Leu Ile Ser Trp Tyr Asp Asn Glu Phe Gly Tyr
305 310 315 320
Ser Asn Arg Val Val Asp Leu Met Ala His Met Ala Ser Lys Glu
325 330 335
<210> 76
<211> 739
<212> PRT
<213> 智人
<400> 76
Met Pro Ser Pro Arg Pro Val Leu Leu Arg Gly Ala Arg Ala Ala Leu
1 5 10 15
Leu Leu Leu Leu Pro Pro Arg Leu Leu Ala Arg Pro Ser Leu Leu Leu
20 25 30
Arg Arg Ser Leu Ser Ala Ala Ser Cys Pro Pro Ile Ser Leu Pro Ala
35 40 45
Ala Ala Ser Arg Ser Ser Met Asp Gly Ala Gly Ala Glu Glu Val Leu
50 55 60
Ala Pro Leu Arg Leu Ala Val Arg Gln Gln Gly Asp Leu Val Arg Lys
65 70 75 80
Leu Lys Glu Asp Lys Ala Pro Gln Val Asp Val Asp Lys Ala Val Ala
85 90 95
Glu Leu Lys Ala Arg Lys Arg Val Leu Glu Ala Lys Glu Leu Ala Leu
100 105 110
Gln Pro Lys Asp Asp Ile Val Asp Arg Ala Lys Met Glu Asp Thr Leu
115 120 125
Lys Arg Arg Phe Phe Tyr Asp Gln Ala Phe Ala Ile Tyr Gly Gly Val
130 135 140
Ser Gly Leu Tyr Asp Phe Gly Pro Val Gly Cys Ala Leu Lys Asn Asn
145 150 155 160
Ile Ile Gln Thr Trp Arg Gln His Phe Ile Gln Glu Glu Gln Ile Leu
165 170 175
Glu Ile Asp Cys Thr Met Leu Thr Pro Glu Pro Val Leu Lys Thr Ser
180 185 190
Gly His Val Asp Lys Phe Ala Asp Phe Met Val Lys Asp Val Lys Asn
195 200 205
Gly Glu Cys Phe Arg Ala Asp His Leu Leu Lys Ala His Leu Gln Lys
210 215 220
Leu Met Ser Asp Lys Lys Cys Ser Val Glu Lys Lys Ser Glu Met Glu
225 230 235 240
Ser Val Leu Ala Gln Leu Asp Asn Tyr Gly Gln Gln Glu Leu Ala Asp
245 250 255
Leu Phe Val Asn Tyr Asn Val Lys Ser Pro Ile Thr Gly Asn Asp Leu
260 265 270
Ser Pro Pro Val Ser Phe Asn Leu Met Phe Lys Thr Phe Ile Gly Pro
275 280 285
Gly Gly Asn Met Pro Gly Tyr Leu Arg Pro Glu Thr Ala Gln Gly Ile
290 295 300
Phe Leu Asn Phe Lys Arg Leu Leu Glu Phe Asn Gln Gly Lys Leu Pro
305 310 315 320
Phe Ala Ala Ala Gln Ile Gly Asn Ser Phe Arg Asn Glu Ile Ser Pro
325 330 335
Arg Ser Gly Leu Ile Arg Val Arg Glu Phe Thr Met Ala Glu Ile Glu
340 345 350
His Phe Val Asp Pro Ser Glu Lys Asp His Pro Lys Phe Gln Asn Val
355 360 365
Ala Asp Leu His Leu Tyr Leu Tyr Ser Ala Lys Ala Gln Val Ser Gly
370 375 380
Gln Ser Ala Arg Lys Met Arg Leu Gly Asp Ala Val Glu Gln Gly Val
385 390 395 400
Ile Asn Asn Thr Val Leu Gly Tyr Phe Ile Gly Arg Ile Tyr Leu Tyr
405 410 415
Leu Thr Lys Val Gly Ile Ser Pro Asp Lys Leu Arg Phe Arg Gln His
420 425 430
Met Glu Asn Glu Met Ala His Tyr Ala Cys Asp Cys Trp Asp Ala Glu
435 440 445
Ser Lys Thr Ser Tyr Gly Trp Ile Glu Ile Val Gly Cys Ala Asp Arg
450 455 460
Ser Cys Tyr Asp Leu Ser Cys His Ala Arg Ala Thr Lys Val Pro Leu
465 470 475 480
Val Ala Glu Lys Pro Leu Lys Glu Pro Lys Thr Val Asn Val Val Gln
485 490 495
Phe Glu Pro Ser Lys Gly Ala Ile Gly Lys Ala Tyr Lys Lys Asp Ala
500 505 510
Lys Leu Val Met Glu Tyr Leu Ala Ile Cys Asp Glu Cys Tyr Ile Thr
515 520 525
Glu Met Glu Met Leu Leu Asn Glu Lys Gly Glu Phe Thr Ile Glu Thr
530 535 540
Glu Gly Lys Thr Phe Gln Leu Thr Lys Asp Met Ile Asn Val Lys Arg
545 550 555 560
Phe Gln Lys Thr Leu Tyr Val Glu Glu Val Val Pro Asn Val Ile Glu
565 570 575
Pro Ser Phe Gly Leu Gly Arg Ile Met Tyr Thr Val Phe Glu His Thr
580 585 590
Phe His Val Arg Glu Gly Asp Glu Gln Arg Thr Phe Phe Ser Phe Pro
595 600 605
Ala Val Val Ala Pro Phe Lys Cys Ser Val Leu Pro Leu Ser Gln Asn
610 615 620
Gln Glu Phe Met Pro Phe Val Lys Glu Leu Ser Glu Ala Leu Thr Arg
625 630 635 640
His Gly Val Ser His Lys Val Asp Asp Ser Ser Gly Ser Ile Gly Arg
645 650 655
Arg Tyr Ala Arg Thr Asp Glu Ile Gly Val Ala Phe Gly Val Thr Ile
660 665 670
Asp Phe Asp Thr Val Asn Lys Thr Pro His Thr Ala Thr Leu Arg Asp
675 680 685
Arg Asp Ser Met Arg Gln Ile Arg Ala Glu Ile Ser Glu Leu Pro Ser
690 695 700
Ile Val Gln Asp Leu Ala Asn Gly Asn Ile Thr Trp Ala Asp Val Glu
705 710 715 720
Ala Arg Tyr Pro Leu Phe Glu Gly Gln Glu Thr Gly Lys Lys Glu Thr
725 730 735
Ile Glu Glu
<210> 77
<211> 308
<212> PRT
<213> 智人
<400> 77
Met Pro Gly Gln Glu Leu Arg Thr Val Asn Gly Ser Gln Met Leu Leu
1 5 10 15
Val Leu Leu Val Leu Ser Trp Leu Pro His Gly Gly Ala Leu Ser Leu
20 25 30
Ala Glu Ala Ser Arg Ala Ser Phe Pro Gly Pro Ser Glu Leu His Ser
35 40 45
Glu Asp Ser Arg Phe Arg Glu Leu Arg Lys Arg Tyr Glu Asp Leu Leu
50 55 60
Thr Arg Leu Arg Ala Asn Gln Ser Trp Glu Asp Ser Asn Thr Asp Leu
65 70 75 80
Val Pro Ala Pro Ala Val Arg Ile Leu Thr Pro Glu Val Arg Leu Gly
85 90 95
Ser Gly Gly His Leu His Leu Arg Ile Ser Arg Ala Ala Leu Pro Glu
100 105 110
Gly Leu Pro Glu Ala Ser Arg Leu His Arg Ala Leu Phe Arg Leu Ser
115 120 125
Pro Thr Ala Ser Arg Ser Trp Asp Val Thr Arg Pro Leu Arg Arg Gln
130 135 140
Leu Ser Leu Ala Arg Pro Gln Ala Pro Ala Leu His Leu Arg Leu Ser
145 150 155 160
Pro Pro Pro Ser Gln Ser Asp Gln Leu Leu Ala Glu Ser Ser Ser Ala
165 170 175
Arg Pro Gln Leu Glu Leu His Leu Arg Pro Gln Ala Ala Arg Gly Arg
180 185 190
Arg Arg Ala Arg Ala Arg Asn Gly Asp His Cys Pro Leu Gly Pro Gly
195 200 205
Arg Cys Cys Arg Leu His Thr Val Arg Ala Ser Leu Glu Asp Leu Gly
210 215 220
Trp Ala Asp Trp Val Leu Ser Pro Arg Glu Val Gln Val Thr Met Cys
225 230 235 240
Ile Gly Ala Cys Pro Ser Gln Phe Arg Ala Ala Asn Met His Ala Gln
245 250 255
Ile Lys Thr Ser Leu His Arg Leu Lys Pro Asp Thr Val Pro Ala Pro
260 265 270
Cys Cys Val Pro Ala Ser Tyr Asn Pro Met Val Leu Ile Gln Lys Thr
275 280 285
Asp Thr Gly Val Ser Leu Gln Thr Tyr Asp Asp Leu Leu Ala Lys Asp
290 295 300
Cys His Cys Ile
305
<210> 78
<211> 782
<212> PRT
<213> 智人
<400> 78
Met Ala Pro His Arg Pro Ala Pro Ala Leu Leu Cys Ala Leu Ser Leu
1 5 10 15
Ala Leu Cys Ala Leu Ser Leu Pro Val Arg Ala Ala Thr Ala Ser Arg
20 25 30
Gly Ala Ser Gln Ala Gly Ala Pro Gln Gly Arg Val Pro Glu Ala Arg
35 40 45
Pro Asn Ser Met Val Val Glu His Pro Glu Phe Leu Lys Ala Gly Lys
50 55 60
Glu Pro Gly Leu Gln Ile Trp Arg Val Glu Lys Phe Asp Leu Val Pro
65 70 75 80
Val Pro Thr Asn Leu Tyr Gly Asp Phe Phe Thr Gly Asp Ala Tyr Val
85 90 95
Ile Leu Lys Thr Val Gln Leu Arg Asn Gly Asn Leu Gln Tyr Asp Leu
100 105 110
His Tyr Trp Leu Gly Asn Glu Cys Ser Gln Asp Glu Ser Gly Ala Ala
115 120 125
Ala Ile Phe Thr Val Gln Leu Asp Asp Tyr Leu Asn Gly Arg Ala Val
130 135 140
Gln His Arg Glu Val Gln Gly Phe Glu Ser Ala Thr Phe Leu Gly Tyr
145 150 155 160
Phe Lys Ser Gly Leu Lys Tyr Lys Lys Gly Gly Val Ala Ser Gly Phe
165 170 175
Lys His Val Val Pro Asn Glu Val Val Val Gln Arg Leu Phe Gln Val
180 185 190
Lys Gly Arg Arg Val Val Arg Ala Thr Glu Val Pro Val Ser Trp Glu
195 200 205
Ser Phe Asn Asn Gly Asp Cys Phe Ile Leu Asp Leu Gly Asn Asn Ile
210 215 220
His Gln Trp Cys Gly Ser Asn Ser Asn Arg Tyr Glu Arg Leu Lys Ala
225 230 235 240
Thr Gln Val Ser Lys Gly Ile Arg Asp Asn Glu Arg Ser Gly Arg Ala
245 250 255
Arg Val His Val Ser Glu Glu Gly Thr Glu Pro Glu Ala Met Leu Gln
260 265 270
Val Leu Gly Pro Lys Pro Ala Leu Pro Ala Gly Thr Glu Asp Thr Ala
275 280 285
Lys Glu Asp Ala Ala Asn Arg Lys Leu Ala Lys Leu Tyr Lys Val Ser
290 295 300
Asn Gly Ala Gly Thr Met Ser Val Ser Leu Val Ala Asp Glu Asn Pro
305 310 315 320
Phe Ala Gln Gly Ala Leu Lys Ser Glu Asp Cys Phe Ile Leu Asp His
325 330 335
Gly Lys Asp Gly Lys Ile Phe Val Trp Lys Gly Lys Gln Ala Asn Thr
340 345 350
Glu Glu Arg Lys Ala Ala Leu Lys Thr Ala Ser Asp Phe Ile Thr Lys
355 360 365
Met Asp Tyr Pro Lys Gln Thr Gln Val Ser Val Leu Pro Glu Gly Gly
370 375 380
Glu Thr Pro Leu Phe Lys Gln Phe Phe Lys Asn Trp Arg Asp Pro Asp
385 390 395 400
Gln Thr Asp Gly Leu Gly Leu Ser Tyr Leu Ser Ser His Ile Ala Asn
405 410 415
Val Glu Arg Val Pro Phe Asp Ala Ala Thr Leu His Thr Ser Thr Ala
420 425 430
Met Ala Ala Gln His Gly Met Asp Asp Asp Gly Thr Gly Gln Lys Gln
435 440 445
Ile Trp Arg Ile Glu Gly Ser Asn Lys Val Pro Val Asp Pro Ala Thr
450 455 460
Tyr Gly Gln Phe Tyr Gly Gly Asp Ser Tyr Ile Ile Leu Tyr Asn Tyr
465 470 475 480
Arg His Gly Gly Arg Gln Gly Gln Ile Ile Tyr Asn Trp Gln Gly Ala
485 490 495
Gln Ser Thr Gln Asp Glu Val Ala Ala Ser Ala Ile Leu Thr Ala Gln
500 505 510
Leu Asp Glu Glu Leu Gly Gly Thr Pro Val Gln Ser Arg Val Val Gln
515 520 525
Gly Lys Glu Pro Ala His Leu Met Ser Leu Phe Gly Gly Lys Pro Met
530 535 540
Ile Ile Tyr Lys Gly Gly Thr Ser Arg Glu Gly Gly Gln Thr Ala Pro
545 550 555 560
Ala Ser Thr Arg Leu Phe Gln Val Arg Ala Asn Ser Ala Gly Ala Thr
565 570 575
Arg Ala Val Glu Val Leu Pro Lys Ala Gly Ala Leu Asn Ser Asn Asp
580 585 590
Ala Phe Val Leu Lys Thr Pro Ser Ala Ala Tyr Leu Trp Val Gly Thr
595 600 605
Gly Ala Ser Glu Ala Glu Lys Thr Gly Ala Gln Glu Leu Leu Arg Val
610 615 620
Leu Arg Ala Gln Pro Val Gln Val Ala Glu Gly Ser Glu Pro Asp Gly
625 630 635 640
Phe Trp Glu Ala Leu Gly Gly Lys Ala Ala Tyr Arg Thr Ser Pro Arg
645 650 655
Leu Lys Asp Lys Lys Met Asp Ala His Pro Pro Arg Leu Phe Ala Cys
660 665 670
Ser Asn Lys Ile Gly Arg Phe Val Ile Glu Glu Val Pro Gly Glu Leu
675 680 685
Met Gln Glu Asp Leu Ala Thr Asp Asp Val Met Leu Leu Asp Thr Trp
690 695 700
Asp Gln Val Phe Val Trp Val Gly Lys Asp Ser Gln Glu Glu Glu Lys
705 710 715 720
Thr Glu Ala Leu Thr Ser Ala Lys Arg Tyr Ile Glu Thr Asp Pro Ala
725 730 735
Asn Arg Asp Arg Arg Thr Pro Ile Thr Val Val Lys Gln Gly Phe Glu
740 745 750
Pro Pro Ser Phe Val Gly Trp Phe Leu Gly Trp Asp Asp Asp Tyr Trp
755 760 765
Ser Val Asp Pro Leu Asp Arg Ala Met Ala Glu Leu Ala Ala
770 775 780
<210> 79
<211> 210
<212> PRT
<213> 智人
<400> 79
Met Pro Pro Tyr Thr Val Val Tyr Phe Pro Val Arg Gly Arg Cys Ala
1 5 10 15
Ala Leu Arg Met Leu Leu Ala Asp Gln Gly Gln Ser Trp Lys Glu Glu
20 25 30
Val Val Thr Val Glu Thr Trp Gln Glu Gly Ser Leu Lys Ala Ser Cys
35 40 45
Leu Tyr Gly Gln Leu Pro Lys Phe Gln Asp Gly Asp Leu Thr Leu Tyr
50 55 60
Gln Ser Asn Thr Ile Leu Arg His Leu Gly Arg Thr Leu Gly Leu Tyr
65 70 75 80
Gly Lys Asp Gln Gln Glu Ala Ala Leu Val Asp Met Val Asn Asp Gly
85 90 95
Val Glu Asp Leu Arg Cys Lys Tyr Ile Ser Leu Ile Tyr Thr Asn Tyr
100 105 110
Glu Ala Gly Lys Asp Asp Tyr Val Lys Ala Leu Pro Gly Gln Leu Lys
115 120 125
Pro Phe Glu Thr Leu Leu Ser Gln Asn Gln Gly Gly Lys Thr Phe Ile
130 135 140
Val Gly Asp Gln Ile Ser Phe Ala Asp Tyr Asn Leu Leu Asp Leu Leu
145 150 155 160
Leu Ile His Glu Val Leu Ala Pro Gly Cys Leu Asp Ala Phe Pro Leu
165 170 175
Leu Ser Ala Tyr Val Gly Arg Leu Ser Ala Arg Pro Lys Leu Lys Ala
180 185 190
Phe Leu Ala Ser Pro Glu Tyr Val Asn Leu Pro Ile Asn Gly Asn Gly
195 200 205
Lys Gln
210
<210> 80
<211> 560
<212> PRT
<213> 智人
<400> 80
Met Phe Ala Arg Met Ser Asp Leu His Val Leu Leu Leu Met Ala Leu
1 5 10 15
Val Gly Lys Thr Ala Cys Gly Phe Ser Leu Met Ser Leu Leu Glu Ser
20 25 30
Leu Asp Pro Asp Trp Thr Pro Asp Gln Tyr Asp Tyr Ser Tyr Glu Asp
35 40 45
Tyr Asn Gln Glu Glu Asn Thr Ser Ser Thr Leu Thr His Ala Glu Asn
50 55 60
Pro Asp Trp Tyr Tyr Thr Glu Asp Gln Ala Asp Pro Cys Gln Pro Asn
65 70 75 80
Pro Cys Glu His Gly Gly Asp Cys Leu Val His Gly Ser Thr Phe Thr
85 90 95
Cys Ser Cys Leu Ala Pro Phe Ser Gly Asn Lys Cys Gln Lys Val Gln
100 105 110
Asn Thr Cys Lys Asp Asn Pro Cys Gly Arg Gly Gln Cys Leu Ile Thr
115 120 125
Gln Ser Pro Pro Tyr Tyr Arg Cys Val Cys Lys His Pro Tyr Thr Gly
130 135 140
Pro Ser Cys Ser Gln Val Val Pro Val Cys Arg Pro Asn Pro Cys Gln
145 150 155 160
Asn Gly Ala Thr Cys Ser Arg His Lys Arg Arg Ser Lys Phe Thr Cys
165 170 175
Ala Cys Pro Asp Gln Phe Lys Gly Lys Phe Cys Glu Ile Gly Ser Asp
180 185 190
Asp Cys Tyr Val Gly Asp Gly Tyr Ser Tyr Arg Gly Lys Met Asn Arg
195 200 205
Thr Val Asn Gln His Ala Cys Leu Tyr Trp Asn Ser His Leu Leu Leu
210 215 220
Gln Glu Asn Tyr Asn Met Phe Met Glu Asp Ala Glu Thr His Gly Ile
225 230 235 240
Gly Glu His Asn Phe Cys Arg Asn Pro Asp Ala Asp Glu Lys Pro Trp
245 250 255
Cys Phe Ile Lys Val Thr Asn Asp Lys Val Lys Trp Glu Tyr Cys Asp
260 265 270
Val Ser Ala Cys Ser Ala Gln Asp Val Ala Tyr Pro Glu Glu Ser Pro
275 280 285
Thr Glu Pro Ser Thr Lys Leu Pro Gly Phe Asp Ser Cys Gly Lys Thr
290 295 300
Glu Ile Ala Glu Arg Lys Ile Lys Arg Ile Tyr Gly Gly Phe Lys Ser
305 310 315 320
Thr Ala Gly Lys His Pro Trp Gln Ala Ser Leu Gln Ser Ser Leu Pro
325 330 335
Leu Thr Ile Ser Met Pro Gln Gly His Phe Cys Gly Gly Ala Leu Ile
340 345 350
His Pro Cys Trp Val Leu Thr Ala Ala His Cys Thr Asp Ile Lys Thr
355 360 365
Arg His Leu Lys Val Val Leu Gly Asp Gln Asp Leu Lys Lys Glu Glu
370 375 380
Phe His Glu Gln Ser Phe Arg Val Glu Lys Ile Phe Lys Tyr Ser His
385 390 395 400
Tyr Asn Glu Arg Asp Glu Ile Pro His Asn Asp Ile Ala Leu Leu Lys
405 410 415
Leu Lys Pro Val Asp Gly His Cys Ala Leu Glu Ser Lys Tyr Val Lys
420 425 430
Thr Val Cys Leu Pro Asp Gly Ser Phe Pro Ser Gly Ser Glu Cys His
435 440 445
Ile Ser Gly Trp Gly Val Thr Glu Thr Gly Lys Gly Ser Arg Gln Leu
450 455 460
Leu Asp Ala Lys Val Lys Leu Ile Ala Asn Thr Leu Cys Asn Ser Arg
465 470 475 480
Gln Leu Tyr Asp His Met Ile Asp Asp Ser Met Ile Cys Ala Gly Asn
485 490 495
Leu Gln Lys Pro Gly Gln Asp Thr Cys Gln Gly Asp Ser Gly Gly Pro
500 505 510
Leu Thr Cys Glu Lys Asp Gly Thr Tyr Tyr Val Tyr Gly Ile Val Ser
515 520 525
Trp Gly Leu Glu Cys Gly Lys Arg Pro Gly Val Tyr Thr Gln Val Thr
530 535 540
Lys Phe Leu Asn Trp Ile Lys Ala Thr Ile Lys Ser Glu Ser Gly Phe
545 550 555 560
<210> 81
<211> 728
<212> PRT
<213> 智人
<400> 81
Met Trp Val Thr Lys Leu Leu Pro Ala Leu Leu Leu Gln His Val Leu
1 5 10 15
Leu His Leu Leu Leu Leu Pro Ile Ala Ile Pro Tyr Ala Glu Gly Gln
20 25 30
Arg Lys Arg Arg Asn Thr Ile His Glu Phe Lys Lys Ser Ala Lys Thr
35 40 45
Thr Leu Ile Lys Ile Asp Pro Ala Leu Lys Ile Lys Thr Lys Lys Val
50 55 60
Asn Thr Ala Asp Gln Cys Ala Asn Arg Cys Thr Arg Asn Lys Gly Leu
65 70 75 80
Pro Phe Thr Cys Lys Ala Phe Val Phe Asp Lys Ala Arg Lys Gln Cys
85 90 95
Leu Trp Phe Pro Phe Asn Ser Met Ser Ser Gly Val Lys Lys Glu Phe
100 105 110
Gly His Glu Phe Asp Leu Tyr Glu Asn Lys Asp Tyr Ile Arg Asn Cys
115 120 125
Ile Ile Gly Lys Gly Arg Ser Tyr Lys Gly Thr Val Ser Ile Thr Lys
130 135 140
Ser Gly Ile Lys Cys Gln Pro Trp Ser Ser Met Ile Pro His Glu His
145 150 155 160
Ser Phe Leu Pro Ser Ser Tyr Arg Gly Lys Asp Leu Gln Glu Asn Tyr
165 170 175
Cys Arg Asn Pro Arg Gly Glu Glu Gly Gly Pro Trp Cys Phe Thr Ser
180 185 190
Asn Pro Glu Val Arg Tyr Glu Val Cys Asp Ile Pro Gln Cys Ser Glu
195 200 205
Val Glu Cys Met Thr Cys Asn Gly Glu Ser Tyr Arg Gly Leu Met Asp
210 215 220
His Thr Glu Ser Gly Lys Ile Cys Gln Arg Trp Asp His Gln Thr Pro
225 230 235 240
His Arg His Lys Phe Leu Pro Glu Arg Tyr Pro Asp Lys Gly Phe Asp
245 250 255
Asp Asn Tyr Cys Arg Asn Pro Asp Gly Gln Pro Arg Pro Trp Cys Tyr
260 265 270
Thr Leu Asp Pro His Thr Arg Trp Glu Tyr Cys Ala Ile Lys Thr Cys
275 280 285
Ala Asp Asn Thr Met Asn Asp Thr Asp Val Pro Leu Glu Thr Thr Glu
290 295 300
Cys Ile Gln Gly Gln Gly Glu Gly Tyr Arg Gly Thr Val Asn Thr Ile
305 310 315 320
Trp Asn Gly Ile Pro Cys Gln Arg Trp Asp Ser Gln Tyr Pro His Glu
325 330 335
His Asp Met Thr Pro Glu Asn Phe Lys Cys Lys Asp Leu Arg Glu Asn
340 345 350
Tyr Cys Arg Asn Pro Asp Gly Ser Glu Ser Pro Trp Cys Phe Thr Thr
355 360 365
Asp Pro Asn Ile Arg Val Gly Tyr Cys Ser Gln Ile Pro Asn Cys Asp
370 375 380
Met Ser His Gly Gln Asp Cys Tyr Arg Gly Asn Gly Lys Asn Tyr Met
385 390 395 400
Gly Asn Leu Ser Gln Thr Arg Ser Gly Leu Thr Cys Ser Met Trp Asp
405 410 415
Lys Asn Met Glu Asp Leu His Arg His Ile Phe Trp Glu Pro Asp Ala
420 425 430
Ser Lys Leu Asn Glu Asn Tyr Cys Arg Asn Pro Asp Asp Asp Ala His
435 440 445
Gly Pro Trp Cys Tyr Thr Gly Asn Pro Leu Ile Pro Trp Asp Tyr Cys
450 455 460
Pro Ile Ser Arg Cys Glu Gly Asp Thr Thr Pro Thr Ile Val Asn Leu
465 470 475 480
Asp His Pro Val Ile Ser Cys Ala Lys Thr Lys Gln Leu Arg Val Val
485 490 495
Asn Gly Ile Pro Thr Arg Thr Asn Ile Gly Trp Met Val Ser Leu Arg
500 505 510
Tyr Arg Asn Lys His Ile Cys Gly Gly Ser Leu Ile Lys Glu Ser Trp
515 520 525
Val Leu Thr Ala Arg Gln Cys Phe Pro Ser Arg Asp Leu Lys Asp Tyr
530 535 540
Glu Ala Trp Leu Gly Ile His Asp Val His Gly Arg Gly Asp Glu Lys
545 550 555 560
Cys Lys Gln Val Leu Asn Val Ser Gln Leu Val Tyr Gly Pro Glu Gly
565 570 575
Ser Asp Leu Val Leu Met Lys Leu Ala Arg Pro Ala Val Leu Asp Asp
580 585 590
Phe Val Ser Thr Ile Asp Leu Pro Asn Tyr Gly Cys Thr Ile Pro Glu
595 600 605
Lys Thr Ser Cys Ser Val Tyr Gly Trp Gly Tyr Thr Gly Leu Ile Asn
610 615 620
Tyr Asp Gly Leu Leu Arg Val Ala His Leu Tyr Ile Met Gly Asn Glu
625 630 635 640
Lys Cys Ser Gln His His Arg Gly Lys Val Thr Leu Asn Glu Ser Glu
645 650 655
Ile Cys Ala Gly Ala Glu Lys Ile Gly Ser Gly Pro Cys Glu Gly Asp
660 665 670
Tyr Gly Gly Pro Leu Val Cys Glu Gln His Lys Met Arg Met Val Leu
675 680 685
Gly Val Ile Val Pro Gly Arg Gly Cys Ala Ile Pro Asn Arg Pro Gly
690 695 700
Ile Phe Val Arg Val Ala Tyr Tyr Ala Lys Trp Ile His Lys Ile Ile
705 710 715 720
Leu Thr Tyr Lys Val Pro Gln Ser
725
<210> 82
<211> 365
<212> PRT
<213> 智人
<400> 82
Met Ala Val Met Ala Pro Arg Thr Leu Val Leu Leu Leu Ser Gly Ala
1 5 10 15
Leu Ala Leu Thr Gln Thr Trp Ala Gly Ser His Ser Met Arg Tyr Phe
20 25 30
Tyr Thr Ser Val Ser Arg Pro Gly Arg Gly Glu Pro Arg Phe Ile Ala
35 40 45
Val Gly Tyr Val Asp Asp Thr Gln Phe Val Arg Phe Asp Ser Asp Ala
50 55 60
Ala Ser Gln Arg Met Glu Pro Arg Ala Pro Trp Ile Glu Gln Glu Gly
65 70 75 80
Pro Glu Tyr Trp Asp Arg Asn Thr Arg Asn Val Lys Ala Gln Ser Gln
85 90 95
Thr Asp Arg Val Asp Leu Gly Thr Leu Arg Gly Tyr Tyr Asn Gln Ser
100 105 110
Glu Ala Gly Ser His Thr Ile Gln Met Met Tyr Gly Cys Asp Val Gly
115 120 125
Ser Asp Gly Arg Phe Leu Arg Gly Tyr Arg Gln Asp Ala Tyr Asp Gly
130 135 140
Lys Asp Tyr Ile Ala Leu Lys Glu Asp Leu Arg Ser Trp Thr Ala Ala
145 150 155 160
Asp Met Ala Ala Gln Thr Thr Lys His Lys Trp Glu Ala Ala His Val
165 170 175
Ala Glu Gln Trp Arg Ala Tyr Leu Glu Gly Thr Cys Val Glu Trp Leu
180 185 190
Arg Arg Tyr Leu Glu Asn Gly Lys Glu Thr Leu Gln Arg Thr Asp Ala
195 200 205
Pro Lys Thr His Met Thr His His Ala Val Ser Asp His Glu Ala Thr
210 215 220
Leu Arg Cys Trp Ala Leu Ser Phe Tyr Pro Ala Glu Ile Thr Leu Thr
225 230 235 240
Trp Gln Arg Asp Gly Glu Asp Gln Thr Gln Asp Thr Glu Leu Val Glu
245 250 255
Thr Arg Pro Ala Gly Asp Gly Thr Phe Gln Lys Trp Val Ala Val Val
260 265 270
Val Pro Ser Gly Gln Glu Gln Arg Tyr Thr Cys His Val Gln His Glu
275 280 285
Gly Leu Pro Lys Pro Leu Thr Leu Arg Trp Glu Pro Ser Ser Gln Pro
290 295 300
Thr Ile Pro Ile Val Gly Ile Ile Ala Gly Leu Val Leu Phe Gly Ala
305 310 315 320
Val Ile Thr Gly Ala Val Val Ala Ala Val Met Trp Arg Arg Lys Ser
325 330 335
Ser Asp Arg Lys Gly Gly Ser Tyr Ser Gln Ala Ala Ser Ser Asp Ser
340 345 350
Ala Gln Gly Ser Asp Val Ser Leu Thr Ala Cys Lys Val
355 360 365
<210> 83
<211> 215
<212> PRT
<213> 智人
<400> 83
Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr
1 5 10 15
Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro
20 25 30
Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Lys Lys Cys Ser Glu Arg
35 40 45
Trp Lys Thr Met Ser Ala Lys Glu Lys Gly Lys Phe Glu Asp Met Ala
50 55 60
Lys Ala Asp Lys Ala Arg Tyr Glu Arg Glu Met Lys Thr Tyr Ile Pro
65 70 75 80
Pro Lys Gly Glu Thr Lys Lys Lys Phe Lys Asp Pro Asn Ala Pro Lys
85 90 95
Arg Pro Pro Ser Ala Phe Phe Leu Phe Cys Ser Glu Tyr Arg Pro Lys
100 105 110
Ile Lys Gly Glu His Pro Gly Leu Ser Ile Gly Asp Val Ala Lys Lys
115 120 125
Leu Gly Glu Met Trp Asn Asn Thr Ala Ala Asp Asp Lys Gln Pro Tyr
130 135 140
Glu Lys Lys Ala Ala Lys Leu Lys Glu Lys Tyr Glu Lys Asp Ile Ala
145 150 155 160
Ala Tyr Arg Ala Lys Gly Lys Pro Asp Ala Ala Lys Lys Gly Val Val
165 170 175
Lys Ala Glu Lys Ser Lys Lys Lys Lys Glu Glu Glu Glu Asp Glu Glu
180 185 190
Asp Glu Glu Asp Glu Glu Glu Glu Glu Asp Glu Glu Asp Glu Asp Glu
195 200 205
Glu Glu Asp Asp Asp Asp Glu
210 215
<210> 84
<211> 372
<212> PRT
<213> 智人
<400> 84
Met Ser Lys Ser Glu Ser Pro Lys Glu Pro Glu Gln Leu Arg Lys Leu
1 5 10 15
Phe Ile Gly Gly Leu Ser Phe Glu Thr Thr Asp Glu Ser Leu Arg Ser
20 25 30
His Phe Glu Gln Trp Gly Thr Leu Thr Asp Cys Val Val Met Arg Asp
35 40 45
Pro Asn Thr Lys Arg Ser Arg Gly Phe Gly Phe Val Thr Tyr Ala Thr
50 55 60
Val Glu Glu Val Asp Ala Ala Met Asn Ala Arg Pro His Lys Val Asp
65 70 75 80
Gly Arg Val Val Glu Pro Lys Arg Ala Val Ser Arg Glu Asp Ser Gln
85 90 95
Arg Pro Gly Ala His Leu Thr Val Lys Lys Ile Phe Val Gly Gly Ile
100 105 110
Lys Glu Asp Thr Glu Glu His His Leu Arg Asp Tyr Phe Glu Gln Tyr
115 120 125
Gly Lys Ile Glu Val Ile Glu Ile Met Thr Asp Arg Gly Ser Gly Lys
130 135 140
Lys Arg Gly Phe Ala Phe Val Thr Phe Asp Asp His Asp Ser Val Asp
145 150 155 160
Lys Ile Val Ile Gln Lys Tyr His Thr Val Asn Gly His Asn Cys Glu
165 170 175
Val Arg Lys Ala Leu Ser Lys Gln Glu Met Ala Ser Ala Ser Ser Ser
180 185 190
Gln Arg Gly Arg Ser Gly Ser Gly Asn Phe Gly Gly Gly Arg Gly Gly
195 200 205
Gly Phe Gly Gly Asn Asp Asn Phe Gly Arg Gly Gly Asn Phe Ser Gly
210 215 220
Arg Gly Gly Phe Gly Gly Ser Arg Gly Gly Gly Gly Tyr Gly Gly Ser
225 230 235 240
Gly Asp Gly Tyr Asn Gly Phe Gly Asn Asp Gly Gly Tyr Gly Gly Gly
245 250 255
Gly Pro Gly Tyr Ser Gly Gly Ser Arg Gly Tyr Gly Ser Gly Gly Gln
260 265 270
Gly Tyr Gly Asn Gln Gly Ser Gly Tyr Gly Gly Ser Gly Ser Tyr Asp
275 280 285
Ser Tyr Asn Asn Gly Gly Gly Gly Gly Phe Gly Gly Gly Ser Gly Ser
290 295 300
Asn Phe Gly Gly Gly Gly Ser Tyr Asn Asp Phe Gly Asn Tyr Asn Asn
305 310 315 320
Gln Ser Ser Asn Phe Gly Pro Met Lys Gly Gly Asn Phe Gly Gly Arg
325 330 335
Ser Ser Gly Pro Tyr Gly Gly Gly Gly Gln Tyr Phe Ala Lys Pro Arg
340 345 350
Asn Gln Gly Gly Tyr Gly Gly Ser Ser Ser Ser Ser Ser Tyr Gly Ser
355 360 365
Gly Arg Arg Phe
370
<210> 85
<211> 353
<212> PRT
<213> 智人
<400> 85
Met Glu Lys Thr Leu Glu Thr Val Pro Leu Glu Arg Lys Lys Arg Glu
1 5 10 15
Lys Glu Gln Phe Arg Lys Leu Phe Ile Gly Gly Leu Ser Phe Glu Thr
20 25 30
Thr Glu Glu Ser Leu Arg Asn Tyr Tyr Glu Gln Trp Gly Lys Leu Thr
35 40 45
Asp Cys Val Val Met Arg Asp Pro Ala Ser Lys Arg Ser Arg Gly Phe
50 55 60
Gly Phe Val Thr Phe Ser Ser Met Ala Glu Val Asp Ala Ala Met Ala
65 70 75 80
Ala Arg Pro His Ser Ile Asp Gly Arg Val Val Glu Pro Lys Arg Ala
85 90 95
Val Ala Arg Glu Glu Ser Gly Lys Pro Gly Ala His Val Thr Val Lys
100 105 110
Lys Leu Phe Val Gly Gly Ile Lys Glu Asp Thr Glu Glu His His Leu
115 120 125
Arg Asp Tyr Phe Glu Glu Tyr Gly Lys Ile Asp Thr Ile Glu Ile Ile
130 135 140
Thr Asp Arg Gln Ser Gly Lys Lys Arg Gly Phe Gly Phe Val Thr Phe
145 150 155 160
Asp Asp His Asp Pro Val Asp Lys Ile Val Leu Gln Lys Tyr His Thr
165 170 175
Ile Asn Gly His Asn Ala Glu Val Arg Lys Ala Leu Ser Arg Gln Glu
180 185 190
Met Gln Glu Val Gln Ser Ser Arg Ser Gly Arg Gly Gly Asn Phe Gly
195 200 205
Phe Gly Asp Ser Arg Gly Gly Gly Gly Asn Phe Gly Pro Gly Pro Gly
210 215 220
Ser Asn Phe Arg Gly Gly Ser Asp Gly Tyr Gly Ser Gly Arg Gly Phe
225 230 235 240
Gly Asp Gly Tyr Asn Gly Tyr Gly Gly Gly Pro Gly Gly Gly Asn Phe
245 250 255
Gly Gly Ser Pro Gly Tyr Gly Gly Gly Arg Gly Gly Tyr Gly Gly Gly
260 265 270
Gly Pro Gly Tyr Gly Asn Gln Gly Gly Gly Tyr Gly Gly Gly Tyr Asp
275 280 285
Asn Tyr Gly Gly Gly Asn Tyr Gly Ser Gly Asn Tyr Asn Asp Phe Gly
290 295 300
Asn Tyr Asn Gln Gln Pro Ser Asn Tyr Gly Pro Met Lys Ser Gly Asn
305 310 315 320
Phe Gly Gly Ser Arg Asn Met Gly Gly Pro Tyr Gly Gly Gly Asn Tyr
325 330 335
Gly Pro Gly Gly Ser Gly Gly Ser Gly Gly Tyr Gly Gly Arg Ser Arg
340 345 350
Tyr
<210> 86
<211> 415
<212> PRT
<213> 智人
<400> 86
Met Met Leu Gly Pro Glu Gly Gly Glu Gly Phe Val Val Lys Leu Arg
1 5 10 15
Gly Leu Pro Trp Ser Cys Ser Val Glu Asp Val Gln Asn Phe Leu Ser
20 25 30
Asp Cys Thr Ile His Asp Gly Ala Ala Gly Val His Phe Ile Tyr Thr
35 40 45
Arg Glu Gly Arg Gln Ser Gly Glu Ala Phe Val Glu Leu Gly Ser Glu
50 55 60
Asp Asp Val Lys Met Ala Leu Lys Lys Asp Arg Glu Ser Met Gly His
65 70 75 80
Arg Tyr Ile Glu Val Phe Lys Ser His Arg Thr Glu Met Asp Trp Val
85 90 95
Leu Lys His Ser Gly Pro Asn Ser Ala Asp Ser Ala Asn Asp Gly Phe
100 105 110
Val Arg Leu Arg Gly Leu Pro Phe Gly Cys Thr Lys Glu Glu Ile Val
115 120 125
Gln Phe Phe Ser Gly Leu Glu Ile Val Pro Asn Gly Ile Thr Leu Pro
130 135 140
Val Asp Pro Glu Gly Lys Ile Thr Gly Glu Ala Phe Val Gln Phe Ala
145 150 155 160
Ser Gln Glu Leu Ala Glu Lys Ala Leu Gly Lys His Lys Glu Arg Ile
165 170 175
Gly His Arg Tyr Ile Glu Val Phe Lys Ser Ser Gln Glu Glu Val Arg
180 185 190
Ser Tyr Ser Asp Pro Pro Leu Lys Phe Met Ser Val Gln Arg Pro Gly
195 200 205
Pro Tyr Asp Arg Pro Gly Thr Ala Arg Arg Tyr Ile Gly Ile Val Lys
210 215 220
Gln Ala Gly Leu Glu Arg Met Arg Pro Gly Ala Tyr Ser Thr Gly Tyr
225 230 235 240
Gly Gly Tyr Glu Glu Tyr Ser Gly Leu Ser Asp Gly Tyr Gly Phe Thr
245 250 255
Thr Asp Leu Phe Gly Arg Asp Leu Ser Tyr Cys Leu Ser Gly Met Tyr
260 265 270
Asp His Arg Tyr Gly Asp Ser Glu Phe Thr Val Gln Ser Thr Thr Gly
275 280 285
His Cys Val His Met Arg Gly Leu Pro Tyr Lys Ala Thr Glu Asn Asp
290 295 300
Ile Tyr Asn Phe Phe Ser Pro Leu Asn Pro Val Arg Val His Ile Glu
305 310 315 320
Ile Gly Pro Asp Gly Arg Val Thr Gly Glu Ala Asp Val Glu Phe Ala
325 330 335
Thr His Glu Glu Ala Val Ala Ala Met Ser Lys Asp Arg Ala Asn Met
340 345 350
Gln His Arg Tyr Ile Glu Leu Phe Leu Asn Ser Thr Thr Gly Ala Ser
355 360 365
Asn Gly Ala Tyr Ser Ser Gln Val Met Gln Gly Met Gly Val Ser Ala
370 375 380
Ala Gln Ala Thr Tyr Ser Gly Leu Glu Ser Gln Ser Val Ser Gly Cys
385 390 395 400
Tyr Gly Ala Gly Tyr Ser Gly Gln Asn Ser Met Gly Gly Tyr Asp
405 410 415
<210> 87
<211> 406
<212> PRT
<213> 智人
<400> 87
Met Ser Ala Leu Gly Ala Val Ile Ala Leu Leu Leu Trp Gly Gln Leu
1 5 10 15
Phe Ala Val Asp Ser Gly Asn Asp Val Thr Asp Ile Ala Asp Asp Gly
20 25 30
Cys Pro Lys Pro Pro Glu Ile Ala His Gly Tyr Val Glu His Ser Val
35 40 45
Arg Tyr Gln Cys Lys Asn Tyr Tyr Lys Leu Arg Thr Glu Gly Asp Gly
50 55 60
Val Tyr Thr Leu Asn Asp Lys Lys Gln Trp Ile Asn Lys Ala Val Gly
65 70 75 80
Asp Lys Leu Pro Glu Cys Glu Ala Asp Asp Gly Cys Pro Lys Pro Pro
85 90 95
Glu Ile Ala His Gly Tyr Val Glu His Ser Val Arg Tyr Gln Cys Lys
100 105 110
Asn Tyr Tyr Lys Leu Arg Thr Glu Gly Asp Gly Val Tyr Thr Leu Asn
115 120 125
Asn Glu Lys Gln Trp Ile Asn Lys Ala Val Gly Asp Lys Leu Pro Glu
130 135 140
Cys Glu Ala Val Cys Gly Lys Pro Lys Asn Pro Ala Asn Pro Val Gln
145 150 155 160
Arg Ile Leu Gly Gly His Leu Asp Ala Lys Gly Ser Phe Pro Trp Gln
165 170 175
Ala Lys Met Val Ser His His Asn Leu Thr Thr Gly Ala Thr Leu Ile
180 185 190
Asn Glu Gln Trp Leu Leu Thr Thr Ala Lys Asn Leu Phe Leu Asn His
195 200 205
Ser Glu Asn Ala Thr Ala Lys Asp Ile Ala Pro Thr Leu Thr Leu Tyr
210 215 220
Val Gly Lys Lys Gln Leu Val Glu Ile Glu Lys Val Val Leu His Pro
225 230 235 240
Asn Tyr Ser Gln Val Asp Ile Gly Leu Ile Lys Leu Lys Gln Lys Val
245 250 255
Ser Val Asn Glu Arg Val Met Pro Ile Cys Leu Pro Ser Lys Asp Tyr
260 265 270
Ala Glu Val Gly Arg Val Gly Tyr Val Ser Gly Trp Gly Arg Asn Ala
275 280 285
Asn Phe Lys Phe Thr Asp His Leu Lys Tyr Val Met Leu Pro Val Ala
290 295 300
Asp Gln Asp Gln Cys Ile Arg His Tyr Glu Gly Ser Thr Val Pro Glu
305 310 315 320
Lys Lys Thr Pro Lys Ser Pro Val Gly Val Gln Pro Ile Leu Asn Glu
325 330 335
His Thr Phe Cys Ala Gly Met Ser Lys Tyr Gln Glu Asp Thr Cys Tyr
340 345 350
Gly Asp Ala Gly Ser Ala Phe Ala Val His Asp Leu Glu Glu Asp Thr
355 360 365
Trp Tyr Ala Thr Gly Ile Leu Ser Phe Asp Lys Ser Cys Ala Val Ala
370 375 380
Glu Tyr Gly Val Tyr Val Lys Val Thr Ser Ile Gln Asp Trp Val Gln
385 390 395 400
Lys Thr Ile Ala Glu Asn
405
<210> 88
<211> 724
<212> PRT
<213> 智人
<400> 88
Met Pro Glu Glu Val His His Gly Glu Glu Glu Val Glu Thr Phe Ala
1 5 10 15
Phe Gln Ala Glu Ile Ala Gln Leu Met Ser Leu Ile Ile Asn Thr Phe
20 25 30
Tyr Ser Asn Lys Glu Ile Phe Leu Arg Glu Leu Ile Ser Asn Ala Ser
35 40 45
Asp Ala Leu Asp Lys Ile Arg Tyr Glu Ser Leu Thr Asp Pro Ser Lys
50 55 60
Leu Asp Ser Gly Lys Glu Leu Lys Ile Asp Ile Ile Pro Asn Pro Gln
65 70 75 80
Glu Arg Thr Leu Thr Leu Val Asp Thr Gly Ile Gly Met Thr Lys Ala
85 90 95
Asp Leu Ile Asn Asn Leu Gly Thr Ile Ala Lys Ser Gly Thr Lys Ala
100 105 110
Phe Met Glu Ala Leu Gln Ala Gly Ala Asp Ile Ser Met Ile Gly Gln
115 120 125
Phe Gly Val Gly Phe Tyr Ser Ala Tyr Leu Val Ala Glu Lys Val Val
130 135 140
Val Ile Thr Lys His Asn Asp Asp Glu Gln Tyr Ala Trp Glu Ser Ser
145 150 155 160
Ala Gly Gly Ser Phe Thr Val Arg Ala Asp His Gly Glu Pro Ile Gly
165 170 175
Arg Gly Thr Lys Val Ile Leu His Leu Lys Glu Asp Gln Thr Glu Tyr
180 185 190
Leu Glu Glu Arg Arg Val Lys Glu Val Val Lys Lys His Ser Gln Phe
195 200 205
Ile Gly Tyr Pro Ile Thr Leu Tyr Leu Glu Lys Glu Arg Glu Lys Glu
210 215 220
Ile Ser Asp Asp Glu Ala Glu Glu Glu Lys Gly Glu Lys Glu Glu Glu
225 230 235 240
Asp Lys Asp Asp Glu Glu Lys Pro Lys Ile Glu Asp Val Gly Ser Asp
245 250 255
Glu Glu Asp Asp Ser Gly Lys Asp Lys Lys Lys Lys Thr Lys Lys Ile
260 265 270
Lys Glu Lys Tyr Ile Asp Gln Glu Glu Leu Asn Lys Thr Lys Pro Ile
275 280 285
Trp Thr Arg Asn Pro Asp Asp Ile Thr Gln Glu Glu Tyr Gly Glu Phe
290 295 300
Tyr Lys Ser Leu Thr Asn Asp Trp Glu Asp His Leu Ala Val Lys His
305 310 315 320
Phe Ser Val Glu Gly Gln Leu Glu Phe Arg Ala Leu Leu Phe Ile Pro
325 330 335
Arg Arg Ala Pro Phe Asp Leu Phe Glu Asn Lys Lys Lys Lys Asn Asn
340 345 350
Ile Lys Leu Tyr Val Arg Arg Val Phe Ile Met Asp Ser Cys Asp Glu
355 360 365
Leu Ile Pro Glu Tyr Leu Asn Phe Ile Arg Gly Val Val Asp Ser Glu
370 375 380
Asp Leu Pro Leu Asn Ile Ser Arg Glu Met Leu Gln Gln Ser Lys Ile
385 390 395 400
Leu Lys Val Ile Arg Lys Asn Ile Val Lys Lys Cys Leu Glu Leu Phe
405 410 415
Ser Glu Leu Ala Glu Asp Lys Glu Asn Tyr Lys Lys Phe Tyr Glu Ala
420 425 430
Phe Ser Lys Asn Leu Lys Leu Gly Ile His Glu Asp Ser Thr Asn Arg
435 440 445
Arg Arg Leu Ser Glu Leu Leu Arg Tyr His Thr Ser Gln Ser Gly Asp
450 455 460
Glu Met Thr Ser Leu Ser Glu Tyr Val Ser Arg Met Lys Glu Thr Gln
465 470 475 480
Lys Ser Ile Tyr Tyr Ile Thr Gly Glu Ser Lys Glu Gln Val Ala Asn
485 490 495
Ser Ala Phe Val Glu Arg Val Arg Lys Arg Gly Phe Glu Val Val Tyr
500 505 510
Met Thr Glu Pro Ile Asp Glu Tyr Cys Val Gln Gln Leu Lys Glu Phe
515 520 525
Asp Gly Lys Ser Leu Val Ser Val Thr Lys Glu Gly Leu Glu Leu Pro
530 535 540
Glu Asp Glu Glu Glu Lys Lys Lys Met Glu Glu Ser Lys Ala Lys Phe
545 550 555 560
Glu Asn Leu Cys Lys Leu Met Lys Glu Ile Leu Asp Lys Lys Val Glu
565 570 575
Lys Val Thr Ile Ser Asn Arg Leu Val Ser Ser Pro Cys Cys Ile Val
580 585 590
Thr Ser Thr Tyr Gly Trp Thr Ala Asn Met Glu Arg Ile Met Lys Ala
595 600 605
Gln Ala Leu Arg Asp Asn Ser Thr Met Gly Tyr Met Met Ala Lys Lys
610 615 620
His Leu Glu Ile Asn Pro Asp His Pro Ile Val Glu Thr Leu Arg Gln
625 630 635 640
Lys Ala Glu Ala Asp Lys Asn Asp Lys Ala Val Lys Asp Leu Val Val
645 650 655
Leu Leu Phe Glu Thr Ala Leu Leu Ser Ser Gly Phe Ser Leu Glu Asp
660 665 670
Pro Gln Thr His Ser Asn Arg Ile Tyr Arg Met Ile Lys Leu Gly Leu
675 680 685
Gly Ile Asp Glu Asp Glu Val Ala Ala Glu Glu Pro Asn Ala Ala Val
690 695 700
Pro Asp Glu Ile Pro Pro Leu Glu Gly Asp Glu Asp Ala Ser Arg Met
705 710 715 720
Glu Glu Val Asp
<210> 89
<211> 803
<212> PRT
<213> 智人
<400> 89
Met Arg Ala Leu Trp Val Leu Gly Leu Cys Cys Val Leu Leu Thr Phe
1 5 10 15
Gly Ser Val Arg Ala Asp Asp Glu Val Asp Val Asp Gly Thr Val Glu
20 25 30
Glu Asp Leu Gly Lys Ser Arg Glu Gly Ser Arg Thr Asp Asp Glu Val
35 40 45
Val Gln Arg Glu Glu Glu Ala Ile Gln Leu Asp Gly Leu Asn Ala Ser
50 55 60
Gln Ile Arg Glu Leu Arg Glu Lys Ser Glu Lys Phe Ala Phe Gln Ala
65 70 75 80
Glu Val Asn Arg Met Met Lys Leu Ile Ile Asn Ser Leu Tyr Lys Asn
85 90 95
Lys Glu Ile Phe Leu Arg Glu Leu Ile Ser Asn Ala Ser Asp Ala Leu
100 105 110
Asp Lys Ile Arg Leu Ile Ser Leu Thr Asp Glu Asn Ala Leu Ser Gly
115 120 125
Asn Glu Glu Leu Thr Val Lys Ile Lys Cys Asp Lys Glu Lys Asn Leu
130 135 140
Leu His Val Thr Asp Thr Gly Val Gly Met Thr Arg Glu Glu Leu Val
145 150 155 160
Lys Asn Leu Gly Thr Ile Ala Lys Ser Gly Thr Ser Glu Phe Leu Asn
165 170 175
Lys Met Thr Glu Ala Gln Glu Asp Gly Gln Ser Thr Ser Glu Leu Ile
180 185 190
Gly Gln Phe Gly Val Gly Phe Tyr Ser Ala Phe Leu Val Ala Asp Lys
195 200 205
Val Ile Val Thr Ser Lys His Asn Asn Asp Thr Gln His Ile Trp Glu
210 215 220
Ser Asp Ser Asn Glu Phe Ser Val Ile Ala Asp Pro Arg Gly Asn Thr
225 230 235 240
Leu Gly Arg Gly Thr Thr Ile Thr Leu Val Leu Lys Glu Glu Ala Ser
245 250 255
Asp Tyr Leu Glu Leu Asp Thr Ile Lys Asn Leu Val Lys Lys Tyr Ser
260 265 270
Gln Phe Ile Asn Phe Pro Ile Tyr Val Trp Ser Ser Lys Thr Glu Thr
275 280 285
Val Glu Glu Pro Met Glu Glu Glu Glu Ala Ala Lys Glu Glu Lys Glu
290 295 300
Glu Ser Asp Asp Glu Ala Ala Val Glu Glu Glu Glu Glu Glu Lys Lys
305 310 315 320
Pro Lys Thr Lys Lys Val Glu Lys Thr Val Trp Asp Trp Glu Leu Met
325 330 335
Asn Asp Ile Lys Pro Ile Trp Gln Arg Pro Ser Lys Glu Val Glu Glu
340 345 350
Asp Glu Tyr Lys Ala Phe Tyr Lys Ser Phe Ser Lys Glu Ser Asp Asp
355 360 365
Pro Met Ala Tyr Ile His Phe Thr Ala Glu Gly Glu Val Thr Phe Lys
370 375 380
Ser Ile Leu Phe Val Pro Thr Ser Ala Pro Arg Gly Leu Phe Asp Glu
385 390 395 400
Tyr Gly Ser Lys Lys Ser Asp Tyr Ile Lys Leu Tyr Val Arg Arg Val
405 410 415
Phe Ile Thr Asp Asp Phe His Asp Met Met Pro Lys Tyr Leu Asn Phe
420 425 430
Val Lys Gly Val Val Asp Ser Asp Asp Leu Pro Leu Asn Val Ser Arg
435 440 445
Glu Thr Leu Gln Gln His Lys Leu Leu Lys Val Ile Arg Lys Lys Leu
450 455 460
Val Arg Lys Thr Leu Asp Met Ile Lys Lys Ile Ala Asp Asp Lys Tyr
465 470 475 480
Asn Asp Thr Phe Trp Lys Glu Phe Gly Thr Asn Ile Lys Leu Gly Val
485 490 495
Ile Glu Asp His Ser Asn Arg Thr Arg Leu Ala Lys Leu Leu Arg Phe
500 505 510
Gln Ser Ser His His Pro Thr Asp Ile Thr Ser Leu Asp Gln Tyr Val
515 520 525
Glu Arg Met Lys Glu Lys Gln Asp Lys Ile Tyr Phe Met Ala Gly Ser
530 535 540
Ser Arg Lys Glu Ala Glu Ser Ser Pro Phe Val Glu Arg Leu Leu Lys
545 550 555 560
Lys Gly Tyr Glu Val Ile Tyr Leu Thr Glu Pro Val Asp Glu Tyr Cys
565 570 575
Ile Gln Ala Leu Pro Glu Phe Asp Gly Lys Arg Phe Gln Asn Val Ala
580 585 590
Lys Glu Gly Val Lys Phe Asp Glu Ser Glu Lys Thr Lys Glu Ser Arg
595 600 605
Glu Ala Val Glu Lys Glu Phe Glu Pro Leu Leu Asn Trp Met Lys Asp
610 615 620
Lys Ala Leu Lys Asp Lys Ile Glu Lys Ala Val Val Ser Gln Arg Leu
625 630 635 640
Thr Glu Ser Pro Cys Ala Leu Val Ala Ser Gln Tyr Gly Trp Ser Gly
645 650 655
Asn Met Glu Arg Ile Met Lys Ala Gln Ala Tyr Gln Thr Gly Lys Asp
660 665 670
Ile Ser Thr Asn Tyr Tyr Ala Ser Gln Lys Lys Thr Phe Glu Ile Asn
675 680 685
Pro Arg His Pro Leu Ile Arg Asp Met Leu Arg Arg Ile Lys Glu Asp
690 695 700
Glu Asp Asp Lys Thr Val Leu Asp Leu Ala Val Val Leu Phe Glu Thr
705 710 715 720
Ala Thr Leu Arg Ser Gly Tyr Leu Leu Pro Asp Thr Lys Ala Tyr Gly
725 730 735
Asp Arg Ile Glu Arg Met Leu Arg Leu Ser Leu Asn Ile Asp Pro Asp
740 745 750
Ala Lys Val Glu Glu Glu Pro Glu Glu Glu Pro Glu Glu Thr Ala Glu
755 760 765
Asp Thr Thr Glu Asp Thr Glu Gln Asp Glu Asp Glu Glu Met Asp Val
770 775 780
Gly Thr Asp Glu Glu Glu Glu Thr Ala Lys Glu Ser Thr Ala Glu Lys
785 790 795 800
Asp Glu Leu
<210> 90
<211> 679
<212> PRT
<213> 智人
<400> 90
Met Ile Ser Ala Ser Arg Ala Ala Ala Ala Arg Leu Val Gly Ala Ala
1 5 10 15
Ala Ser Arg Gly Pro Thr Ala Ala Arg His Gln Asp Ser Trp Asn Gly
20 25 30
Leu Ser His Glu Ala Phe Arg Leu Val Ser Arg Arg Asp Tyr Ala Ser
35 40 45
Glu Ala Ile Lys Gly Ala Val Val Gly Ile Asp Leu Gly Thr Thr Asn
50 55 60
Ser Cys Val Ala Val Met Glu Gly Lys Gln Ala Lys Val Leu Glu Asn
65 70 75 80
Ala Glu Gly Ala Arg Thr Thr Pro Ser Val Val Ala Phe Thr Ala Asp
85 90 95
Gly Glu Arg Leu Val Gly Met Pro Ala Lys Arg Gln Ala Val Thr Asn
100 105 110
Pro Asn Asn Thr Phe Tyr Ala Thr Lys Arg Leu Ile Gly Arg Arg Tyr
115 120 125
Asp Asp Pro Glu Val Gln Lys Asp Ile Lys Asn Val Pro Phe Lys Ile
130 135 140
Val Arg Ala Ser Asn Gly Asp Ala Trp Val Glu Ala His Gly Lys Leu
145 150 155 160
Tyr Ser Pro Ser Gln Ile Gly Ala Phe Val Leu Met Lys Met Lys Glu
165 170 175
Thr Ala Glu Asn Tyr Leu Gly His Thr Ala Lys Asn Ala Val Ile Thr
180 185 190
Val Pro Ala Tyr Phe Asn Asp Ser Gln Arg Gln Ala Thr Lys Asp Ala
195 200 205
Gly Gln Ile Ser Gly Leu Asn Val Leu Arg Val Ile Asn Glu Pro Thr
210 215 220
Ala Ala Ala Leu Ala Tyr Gly Leu Asp Lys Ser Glu Asp Lys Val Ile
225 230 235 240
Ala Val Tyr Asp Leu Gly Gly Gly Thr Phe Asp Ile Ser Ile Leu Glu
245 250 255
Ile Gln Lys Gly Val Phe Glu Val Lys Ser Thr Asn Gly Asp Thr Phe
260 265 270
Leu Gly Gly Glu Asp Phe Asp Gln Ala Leu Leu Arg His Ile Val Lys
275 280 285
Glu Phe Lys Arg Glu Thr Gly Val Asp Leu Thr Lys Asp Asn Met Ala
290 295 300
Leu Gln Arg Val Arg Glu Ala Ala Glu Lys Ala Lys Cys Glu Leu Ser
305 310 315 320
Ser Ser Val Gln Thr Asp Ile Asn Leu Pro Tyr Leu Thr Met Asp Ser
325 330 335
Ser Gly Pro Lys His Leu Asn Met Lys Leu Thr Arg Ala Gln Phe Glu
340 345 350
Gly Ile Val Thr Asp Leu Ile Arg Arg Thr Ile Ala Pro Cys Gln Lys
355 360 365
Ala Met Gln Asp Ala Glu Val Ser Lys Ser Asp Ile Gly Glu Val Ile
370 375 380
Leu Val Gly Gly Met Thr Arg Met Pro Lys Val Gln Gln Thr Val Gln
385 390 395 400
Asp Leu Phe Gly Arg Ala Pro Ser Lys Ala Val Asn Pro Asp Glu Ala
405 410 415
Val Ala Ile Gly Ala Ala Ile Gln Gly Gly Val Leu Ala Gly Asp Val
420 425 430
Thr Asp Val Leu Leu Leu Asp Val Thr Pro Leu Ser Leu Gly Ile Glu
435 440 445
Thr Leu Gly Gly Val Phe Thr Lys Leu Ile Asn Arg Asn Thr Thr Ile
450 455 460
Pro Thr Lys Lys Ser Gln Val Phe Ser Thr Ala Ala Asp Gly Gln Thr
465 470 475 480
Gln Val Glu Ile Lys Val Cys Gln Gly Glu Arg Glu Met Ala Gly Asp
485 490 495
Asn Lys Leu Leu Gly Gln Phe Thr Leu Ile Gly Ile Pro Pro Ala Pro
500 505 510
Arg Gly Val Pro Gln Ile Glu Val Thr Phe Asp Ile Asp Ala Asn Gly
515 520 525
Ile Val His Val Ser Ala Lys Asp Lys Gly Thr Gly Arg Glu Gln Gln
530 535 540
Ile Val Ile Gln Ser Ser Gly Gly Leu Ser Lys Asp Asp Ile Glu Asn
545 550 555 560
Met Val Lys Asn Ala Glu Lys Tyr Ala Glu Glu Asp Arg Arg Lys Lys
565 570 575
Glu Arg Val Glu Ala Val Asn Met Ala Glu Gly Ile Ile His Asp Thr
580 585 590
Glu Thr Lys Met Glu Glu Phe Lys Asp Gln Leu Pro Ala Asp Glu Cys
595 600 605
Asn Lys Leu Lys Glu Glu Ile Ser Lys Met Arg Glu Leu Leu Ala Arg
610 615 620
Lys Asp Ser Glu Thr Gly Glu Asn Ile Arg Gln Ala Ala Ser Ser Leu
625 630 635 640
Gln Gln Ala Ser Leu Lys Leu Phe Glu Met Ala Tyr Lys Lys Met Ala
645 650 655
Ser Glu Arg Glu Gly Ser Gly Ser Ser Gly Thr Gly Glu Gln Lys Glu
660 665 670
Asp Gln Lys Glu Glu Lys Gln
675
<210> 91
<211> 205
<212> PRT
<213> 智人
<400> 91
Met Thr Glu Arg Arg Val Pro Phe Ser Leu Leu Arg Gly Pro Ser Trp
1 5 10 15
Asp Pro Phe Arg Asp Trp Tyr Pro His Ser Arg Leu Phe Asp Gln Ala
20 25 30
Phe Gly Leu Pro Arg Leu Pro Glu Glu Trp Ser Gln Trp Leu Gly Gly
35 40 45
Ser Ser Trp Pro Gly Tyr Val Arg Pro Leu Pro Pro Ala Ala Ile Glu
50 55 60
Ser Pro Ala Val Ala Ala Pro Ala Tyr Ser Arg Ala Leu Ser Arg Gln
65 70 75 80
Leu Ser Ser Gly Val Ser Glu Ile Arg His Thr Ala Asp Arg Trp Arg
85 90 95
Val Ser Leu Asp Val Asn His Phe Ala Pro Asp Glu Leu Thr Val Lys
100 105 110
Thr Lys Asp Gly Val Val Glu Ile Thr Gly Lys His Glu Glu Arg Gln
115 120 125
Asp Glu His Gly Tyr Ile Ser Arg Cys Phe Thr Arg Lys Tyr Thr Leu
130 135 140
Pro Pro Gly Val Asp Pro Thr Gln Val Ser Ser Ser Leu Ser Pro Glu
145 150 155 160
Gly Thr Leu Thr Val Glu Ala Pro Met Pro Lys Leu Ala Thr Gln Ser
165 170 175
Asn Glu Ile Thr Ile Pro Val Thr Phe Glu Ser Arg Ala Gln Leu Gly
180 185 190
Gly Pro Glu Ala Ala Lys Ser Asp Glu Thr Ala Ala Lys
195 200 205
<210> 92
<211> 573
<212> PRT
<213> 智人
<400> 92
Met Leu Arg Leu Pro Thr Val Phe Arg Gln Met Arg Pro Val Ser Arg
1 5 10 15
Val Leu Ala Pro His Leu Thr Arg Ala Tyr Ala Lys Asp Val Lys Phe
20 25 30
Gly Ala Asp Ala Arg Ala Leu Met Leu Gln Gly Val Asp Leu Leu Ala
35 40 45
Asp Ala Val Ala Val Thr Met Gly Pro Lys Gly Arg Thr Val Ile Ile
50 55 60
Glu Gln Ser Trp Gly Ser Pro Lys Val Thr Lys Asp Gly Val Thr Val
65 70 75 80
Ala Lys Ser Ile Asp Leu Lys Asp Lys Tyr Lys Asn Ile Gly Ala Lys
85 90 95
Leu Val Gln Asp Val Ala Asn Asn Thr Asn Glu Glu Ala Gly Asp Gly
100 105 110
Thr Thr Thr Ala Thr Val Leu Ala Arg Ser Ile Ala Lys Glu Gly Phe
115 120 125
Glu Lys Ile Ser Lys Gly Ala Asn Pro Val Glu Ile Arg Arg Gly Val
130 135 140
Met Leu Ala Val Asp Ala Val Ile Ala Glu Leu Lys Lys Gln Ser Lys
145 150 155 160
Pro Val Thr Thr Pro Glu Glu Ile Ala Gln Val Ala Thr Ile Ser Ala
165 170 175
Asn Gly Asp Lys Glu Ile Gly Asn Ile Ile Ser Asp Ala Met Lys Lys
180 185 190
Val Gly Arg Lys Gly Val Ile Thr Val Lys Asp Gly Lys Thr Leu Asn
195 200 205
Asp Glu Leu Glu Ile Ile Glu Gly Met Lys Phe Asp Arg Gly Tyr Ile
210 215 220
Ser Pro Tyr Phe Ile Asn Thr Ser Lys Gly Gln Lys Cys Glu Phe Gln
225 230 235 240
Asp Ala Tyr Val Leu Leu Ser Glu Lys Lys Ile Ser Ser Ile Gln Ser
245 250 255
Ile Val Pro Ala Leu Glu Ile Ala Asn Ala His Arg Lys Pro Leu Val
260 265 270
Ile Ile Ala Glu Asp Val Asp Gly Glu Ala Leu Ser Thr Leu Val Leu
275 280 285
Asn Arg Leu Lys Val Gly Leu Gln Val Val Ala Val Lys Ala Pro Gly
290 295 300
Phe Gly Asp Asn Arg Lys Asn Gln Leu Lys Asp Met Ala Ile Ala Thr
305 310 315 320
Gly Gly Ala Val Phe Gly Glu Glu Gly Leu Thr Leu Asn Leu Glu Asp
325 330 335
Val Gln Pro His Asp Leu Gly Lys Val Gly Glu Val Ile Val Thr Lys
340 345 350
Asp Asp Ala Met Leu Leu Lys Gly Lys Gly Asp Lys Ala Gln Ile Glu
355 360 365
Lys Arg Ile Gln Glu Ile Ile Glu Gln Leu Asp Val Thr Thr Ser Glu
370 375 380
Tyr Glu Lys Glu Lys Leu Asn Glu Arg Leu Ala Lys Leu Ser Asp Gly
385 390 395 400
Val Ala Val Leu Lys Val Gly Gly Thr Ser Asp Val Glu Val Asn Glu
405 410 415
Lys Lys Asp Arg Val Thr Asp Ala Leu Asn Ala Thr Arg Ala Ala Val
420 425 430
Glu Glu Gly Ile Val Leu Gly Gly Gly Cys Ala Leu Leu Arg Cys Ile
435 440 445
Pro Ala Leu Asp Ser Leu Thr Pro Ala Asn Glu Asp Gln Lys Ile Gly
450 455 460
Ile Glu Ile Ile Lys Arg Thr Leu Lys Ile Pro Ala Met Thr Ile Ala
465 470 475 480
Lys Asn Ala Gly Val Glu Gly Ser Leu Ile Val Glu Lys Ile Met Gln
485 490 495
Ser Ser Ser Glu Val Gly Tyr Asp Ala Met Ala Gly Asp Phe Val Asn
500 505 510
Met Val Glu Lys Gly Ile Ile Asp Pro Thr Lys Val Val Arg Thr Ala
515 520 525
Leu Leu Asp Ala Ala Gly Val Ala Ser Leu Leu Thr Thr Ala Glu Val
530 535 540
Val Val Thr Glu Ile Pro Lys Glu Glu Lys Asp Pro Gly Met Gly Ala
545 550 555 560
Met Gly Gly Met Gly Gly Gly Met Gly Gly Gly Met Phe
565 570
<210> 93
<211> 317
<212> PRT
<213> 智人
<400> 93
Met Lys Thr Ala Leu Ile Leu Leu Ser Ile Leu Gly Met Ala Cys Ala
1 5 10 15
Phe Ser Met Lys Asn Leu His Arg Arg Val Lys Ile Glu Asp Ser Glu
20 25 30
Glu Asn Gly Val Phe Lys Tyr Arg Pro Arg Tyr Tyr Leu Tyr Lys His
35 40 45
Ala Tyr Phe Tyr Pro His Leu Lys Arg Phe Pro Val Gln Gly Ser Ser
50 55 60
Asp Ser Ser Glu Glu Asn Gly Asp Asp Ser Ser Glu Glu Glu Glu Glu
65 70 75 80
Glu Glu Glu Thr Ser Asn Glu Gly Glu Asn Asn Glu Glu Ser Asn Glu
85 90 95
Asp Glu Asp Ser Glu Ala Glu Asn Thr Thr Leu Ser Ala Thr Thr Leu
100 105 110
Gly Tyr Gly Glu Asp Ala Thr Pro Gly Thr Gly Tyr Thr Gly Leu Ala
115 120 125
Ala Ile Gln Leu Pro Lys Lys Ala Gly Asp Ile Thr Asn Lys Ala Thr
130 135 140
Lys Glu Lys Glu Ser Asp Glu Glu Glu Glu Glu Glu Glu Glu Gly Asn
145 150 155 160
Glu Asn Glu Glu Ser Glu Ala Glu Val Asp Glu Asn Glu Gln Gly Ile
165 170 175
Asn Gly Thr Ser Thr Asn Ser Thr Glu Ala Glu Asn Gly Asn Gly Ser
180 185 190
Ser Gly Gly Asp Asn Gly Glu Glu Gly Glu Glu Glu Ser Val Thr Gly
195 200 205
Ala Asn Ala Glu Asp Thr Thr Glu Thr Gly Arg Gln Gly Lys Gly Thr
210 215 220
Ser Lys Thr Thr Thr Ser Pro Asn Gly Gly Phe Glu Pro Thr Thr Pro
225 230 235 240
Pro Gln Val Tyr Arg Thr Thr Ser Pro Pro Phe Gly Lys Thr Thr Thr
245 250 255
Val Glu Tyr Glu Gly Glu Tyr Glu Tyr Thr Gly Ala Asn Glu Tyr Asp
260 265 270
Asn Gly Tyr Glu Ile Tyr Glu Ser Glu Asn Gly Glu Pro Arg Gly Asp
275 280 285
Asn Tyr Arg Ala Tyr Glu Asp Glu Tyr Ser Tyr Phe Lys Gly Gln Gly
290 295 300
Tyr Asp Gly Tyr Asp Gly Gln Asn Tyr Tyr His His Gln
305 310 315
<210> 94
<211> 600
<212> PRT
<213> 智人
<400> 94
Met Ala Ser Asn His Lys Ser Ser Ala Ala Arg Pro Val Ser Arg Gly
1 5 10 15
Gly Val Gly Leu Thr Gly Arg Pro Pro Ser Gly Ile Arg Pro Leu Ser
20 25 30
Gly Asn Ile Arg Val Ala Thr Ala Met Pro Pro Gly Thr Ala Arg Pro
35 40 45
Gly Ser Arg Gly Cys Pro Ile Gly Thr Gly Gly Val Leu Ser Ser Gln
50 55 60
Ile Lys Val Ala His Arg Pro Val Thr Gln Gln Gly Leu Thr Gly Met
65 70 75 80
Lys Thr Gly Thr Lys Gly Pro Gln Arg Gln Ile Leu Asp Lys Ser Tyr
85 90 95
Tyr Leu Gly Leu Leu Arg Ser Lys Ile Ser Glu Leu Thr Thr Glu Val
100 105 110
Asn Lys Leu Gln Lys Gly Ile Glu Met Tyr Asn Gln Glu Asn Ser Val
115 120 125
Tyr Leu Ser Tyr Glu Lys Arg Ala Glu Thr Leu Ala Val Glu Ile Lys
130 135 140
Glu Leu Gln Gly Gln Leu Ala Asp Tyr Asn Met Leu Val Asp Lys Leu
145 150 155 160
Asn Thr Asn Thr Glu Met Glu Glu Val Met Asn Asp Tyr Asn Met Leu
165 170 175
Lys Ala Gln Asn Asp Arg Glu Thr Gln Ser Leu Asp Val Ile Phe Thr
180 185 190
Glu Arg Gln Ala Lys Glu Lys Gln Ile Arg Ser Val Glu Glu Glu Ile
195 200 205
Glu Gln Glu Lys Gln Ala Thr Asp Asp Ile Ile Lys Asn Met Ser Phe
210 215 220
Glu Asn Gln Val Lys Tyr Leu Glu Met Lys Thr Thr Asn Glu Lys Leu
225 230 235 240
Leu Gln Glu Leu Asp Thr Leu Gln Gln Gln Leu Asp Ser Gln Asn Met
245 250 255
Lys Lys Glu Ser Leu Glu Ala Glu Ile Ala His Ser Gln Val Lys Gln
260 265 270
Glu Ala Val Leu Leu His Glu Lys Leu Tyr Glu Leu Glu Ser His Arg
275 280 285
Asp Gln Met Ile Ala Glu Asp Lys Ser Ile Gly Ser Pro Met Glu Glu
290 295 300
Arg Glu Lys Leu Leu Lys Gln Ile Lys Asp Asp Asn Gln Glu Ile Ala
305 310 315 320
Ser Met Glu Arg Gln Leu Thr Asp Thr Lys Glu Lys Ile Asn Gln Phe
325 330 335
Ile Glu Glu Ile Arg Gln Leu Asp Met Asp Leu Glu Glu His Gln Gly
340 345 350
Glu Met Asn Gln Lys Tyr Lys Glu Leu Lys Lys Arg Glu Glu His Met
355 360 365
Asp Thr Phe Ile Glu Thr Phe Glu Glu Thr Lys Asn Gln Glu Leu Lys
370 375 380
Arg Lys Ala Gln Ile Glu Ala Asn Ile Val Ala Leu Leu Glu His Cys
385 390 395 400
Ser Arg Asn Ile Asn Arg Ile Glu Gln Ile Ser Ser Ile Thr Asn Gln
405 410 415
Glu Leu Lys Met Met Gln Asp Asp Leu Asn Phe Lys Ser Thr Glu Val
420 425 430
Gln Lys Ser Gln Ser Thr Ala Gln Asn Leu Thr Ser Asp Ile Gln Arg
435 440 445
Leu Gln Leu Asp Leu Gln Lys Met Glu Leu Leu Glu Ser Lys Met Thr
450 455 460
Glu Glu Gln His Ser Leu Lys Ser Lys Ile Lys Gln Met Thr Thr Asp
465 470 475 480
Leu Glu Ile Tyr Asn Asp Leu Pro Ala Leu Lys Ser Ser Gly Glu Glu
485 490 495
Lys Ile Lys Lys Leu His Gln Glu Arg Met Ile Leu Ser Thr His Arg
500 505 510
Asn Ala Phe Lys Lys Ile Met Glu Lys Gln Asn Ile Glu Tyr Glu Ala
515 520 525
Leu Lys Thr Gln Leu Gln Glu Asn Glu Thr His Ser Gln Leu Thr Asn
530 535 540
Leu Glu Arg Lys Trp Gln His Leu Glu Gln Asn Asn Phe Ala Met Lys
545 550 555 560
Glu Phe Ile Ala Thr Lys Ser Gln Glu Ser Asp Tyr Gln Pro Ile Lys
565 570 575
Lys Asn Val Thr Lys Gln Ile Ala Glu Tyr Asn Lys Thr Ile Val Asp
580 585 590
Ala Leu His Ser Thr Ser Gly Asn
595 600
<210> 95
<211> 195
<212> PRT
<213> 智人
<400> 95
Met Gly Lys Ile Ser Ser Leu Pro Thr Gln Leu Phe Lys Cys Cys Phe
1 5 10 15
Cys Asp Phe Leu Lys Val Lys Met His Thr Met Ser Ser Ser His Leu
20 25 30
Phe Tyr Leu Ala Leu Cys Leu Leu Thr Phe Thr Ser Ser Ala Thr Ala
35 40 45
Gly Pro Glu Thr Leu Cys Gly Ala Glu Leu Val Asp Ala Leu Gln Phe
50 55 60
Val Cys Gly Asp Arg Gly Phe Tyr Phe Asn Lys Pro Thr Gly Tyr Gly
65 70 75 80
Ser Ser Ser Arg Arg Ala Pro Gln Thr Gly Ile Val Asp Glu Cys Cys
85 90 95
Phe Arg Ser Cys Asp Leu Arg Arg Leu Glu Met Tyr Cys Ala Pro Leu
100 105 110
Lys Pro Ala Lys Ser Ala Arg Ser Val Arg Ala Gln Arg His Thr Asp
115 120 125
Met Pro Lys Thr Gln Lys Tyr Gln Pro Pro Ser Thr Asn Lys Asn Thr
130 135 140
Lys Ser Gln Arg Arg Lys Gly Trp Pro Lys Thr His Pro Gly Gly Glu
145 150 155 160
Gln Lys Glu Gly Thr Glu Ala Ser Leu Gln Ile Arg Gly Lys Lys Lys
165 170 175
Glu Gln Arg Arg Glu Ile Gly Ser Arg Asn Ala Glu Cys Arg Gly Lys
180 185 190
Lys Gly Lys
195
<210> 96
<211> 340
<212> PRT
<213> 智人
<400> 96
Ala Ser Pro Thr Ser Pro Lys Val Phe Pro Leu Ser Leu Asp Ser Thr
1 5 10 15
Pro Gln Asp Gly Asn Val Val Val Ala Cys Leu Val Gln Gly Phe Phe
20 25 30
Pro Gln Glu Pro Leu Ser Val Thr Trp Ser Glu Ser Gly Gln Asn Val
35 40 45
Thr Ala Arg Asn Phe Pro Pro Ser Gln Asp Ala Ser Gly Asp Leu Tyr
50 55 60
Thr Thr Ser Ser Gln Leu Thr Leu Pro Ala Thr Gln Cys Pro Asp Gly
65 70 75 80
Lys Ser Val Thr Cys His Val Lys His Tyr Thr Asn Pro Ser Gln Asp
85 90 95
Val Thr Val Pro Cys Pro Val Pro Pro Pro Pro Pro Cys Cys His Pro
100 105 110
Arg Leu Ser Leu His Arg Pro Ala Leu Glu Asp Leu Leu Leu Gly Ser
115 120 125
Glu Ala Asn Leu Thr Cys Thr Leu Thr Gly Leu Arg Asp Ala Ser Gly
130 135 140
Ala Thr Phe Thr Trp Thr Pro Ser Ser Gly Lys Ser Ala Val Gln Gly
145 150 155 160
Pro Pro Glu Arg Asp Leu Cys Gly Cys Tyr Ser Val Ser Ser Val Leu
165 170 175
Pro Gly Cys Ala Gln Pro Trp Asn His Gly Glu Thr Phe Thr Cys Thr
180 185 190
Ala Ala His Pro Glu Leu Lys Thr Pro Leu Thr Ala Asn Ile Thr Lys
195 200 205
Ser Gly Asn Thr Phe Arg Pro Glu Val His Leu Leu Pro Pro Pro Ser
210 215 220
Glu Glu Leu Ala Leu Asn Glu Leu Val Thr Leu Thr Cys Leu Ala Arg
225 230 235 240
Gly Phe Ser Pro Lys Asp Val Leu Val Arg Trp Leu Gln Gly Ser Gln
245 250 255
Glu Leu Pro Arg Glu Lys Tyr Leu Thr Trp Ala Ser Arg Gln Glu Pro
260 265 270
Ser Gln Gly Thr Thr Thr Phe Ala Val Thr Ser Ile Leu Arg Val Ala
275 280 285
Ala Glu Asp Trp Lys Lys Gly Asp Thr Phe Ser Cys Met Val Gly His
290 295 300
Glu Ala Leu Pro Leu Ala Phe Thr Gln Lys Thr Ile Asp Arg Met Ala
305 310 315 320
Gly Lys Pro Thr His Val Asn Val Ser Val Val Met Ala Glu Val Asp
325 330 335
Gly Thr Cys Tyr
340
<210> 97
<211> 551
<212> PRT
<213> 智人
<400> 97
Met Ala Ala Pro Ala Leu Ser Trp Arg Leu Pro Leu Leu Ile Leu Leu
1 5 10 15
Leu Pro Leu Ala Thr Ser Trp Ala Ser Ala Ala Val Asn Gly Thr Ser
20 25 30
Gln Phe Thr Cys Phe Tyr Asn Ser Arg Ala Asn Ile Ser Cys Val Trp
35 40 45
Ser Gln Asp Gly Ala Leu Gln Asp Thr Ser Cys Gln Val His Ala Trp
50 55 60
Pro Asp Arg Arg Arg Trp Asn Gln Thr Cys Glu Leu Leu Pro Val Ser
65 70 75 80
Gln Ala Ser Trp Ala Cys Asn Leu Ile Leu Gly Ala Pro Asp Ser Gln
85 90 95
Lys Leu Thr Thr Val Asp Ile Val Thr Leu Arg Val Leu Cys Arg Glu
100 105 110
Gly Val Arg Trp Arg Val Met Ala Ile Gln Asp Phe Lys Pro Phe Glu
115 120 125
Asn Leu Arg Leu Met Ala Pro Ile Ser Leu Gln Val Val His Val Glu
130 135 140
Thr His Arg Cys Asn Ile Ser Trp Glu Ile Ser Gln Ala Ser His Tyr
145 150 155 160
Phe Glu Arg His Leu Glu Phe Glu Ala Arg Thr Leu Ser Pro Gly His
165 170 175
Thr Trp Glu Glu Ala Pro Leu Leu Thr Leu Lys Gln Lys Gln Glu Trp
180 185 190
Ile Cys Leu Glu Thr Leu Thr Pro Asp Thr Gln Tyr Glu Phe Gln Val
195 200 205
Arg Val Lys Pro Leu Gln Gly Glu Phe Thr Thr Trp Ser Pro Trp Ser
210 215 220
Gln Pro Leu Ala Phe Arg Thr Lys Pro Ala Ala Leu Gly Lys Asp Thr
225 230 235 240
Ile Pro Trp Leu Gly His Leu Leu Val Gly Leu Ser Gly Ala Phe Gly
245 250 255
Phe Ile Ile Leu Val Tyr Leu Leu Ile Asn Cys Arg Asn Thr Gly Pro
260 265 270
Trp Leu Lys Lys Val Leu Lys Cys Asn Thr Pro Asp Pro Ser Lys Phe
275 280 285
Phe Ser Gln Leu Ser Ser Glu His Gly Gly Asp Val Gln Lys Trp Leu
290 295 300
Ser Ser Pro Phe Pro Ser Ser Ser Phe Ser Pro Gly Gly Leu Ala Pro
305 310 315 320
Glu Ile Ser Pro Leu Glu Val Leu Glu Arg Asp Lys Val Thr Gln Leu
325 330 335
Leu Leu Gln Gln Asp Lys Val Pro Glu Pro Ala Ser Leu Ser Ser Asn
340 345 350
His Ser Leu Thr Ser Cys Phe Thr Asn Gln Gly Tyr Phe Phe Phe His
355 360 365
Leu Pro Asp Ala Leu Glu Ile Glu Ala Cys Gln Val Tyr Phe Thr Tyr
370 375 380
Asp Pro Tyr Ser Glu Glu Asp Pro Asp Glu Gly Val Ala Gly Ala Pro
385 390 395 400
Thr Gly Ser Ser Pro Gln Pro Leu Gln Pro Leu Ser Gly Glu Asp Asp
405 410 415
Ala Tyr Cys Thr Phe Pro Ser Arg Asp Asp Leu Leu Leu Phe Ser Pro
420 425 430
Ser Leu Leu Gly Gly Pro Ser Pro Pro Ser Thr Ala Pro Gly Gly Ser
435 440 445
Gly Ala Gly Glu Glu Arg Met Pro Pro Ser Leu Gln Glu Arg Val Pro
450 455 460
Arg Asp Trp Asp Pro Gln Pro Leu Gly Pro Pro Thr Pro Gly Val Pro
465 470 475 480
Asp Leu Val Asp Phe Gln Pro Pro Pro Glu Leu Val Leu Arg Glu Ala
485 490 495
Gly Glu Glu Val Pro Asp Ala Gly Pro Arg Glu Gly Val Ser Phe Pro
500 505 510
Trp Ser Arg Pro Pro Gly Gln Gly Glu Phe Arg Ala Leu Asn Ala Arg
515 520 525
Leu Pro Leu Asn Thr Asp Ala Tyr Leu Ser Leu Gln Glu Leu Gln Gly
530 535 540
Gln Asp Pro Thr His Leu Val
545 550
<210> 98
<211> 99
<212> PRT
<213> 智人
<400> 98
Met Thr Ser Lys Leu Ala Val Ala Leu Leu Ala Ala Phe Leu Ile Ser
1 5 10 15
Ala Ala Leu Cys Glu Gly Ala Val Leu Pro Arg Ser Ala Lys Glu Leu
20 25 30
Arg Cys Gln Cys Ile Lys Thr Tyr Ser Lys Pro Phe His Pro Lys Phe
35 40 45
Ile Lys Glu Leu Arg Val Ile Glu Ser Gly Pro His Cys Ala Asn Thr
50 55 60
Glu Ile Ile Val Lys Leu Ser Asp Gly Arg Glu Leu Cys Leu Asp Pro
65 70 75 80
Lys Glu Asn Trp Val Gln Arg Val Val Glu Lys Phe Leu Lys Arg Ala
85 90 95
Glu Asn Ser
<210> 99
<211> 144
<212> PRT
<213> 智人
<400> 99
Met Leu Leu Ala Met Val Leu Thr Ser Ala Leu Leu Leu Cys Ser Val
1 5 10 15
Ala Gly Gln Gly Cys Pro Thr Leu Ala Gly Ile Leu Asp Ile Asn Phe
20 25 30
Leu Ile Asn Lys Met Gln Glu Asp Pro Ala Ser Lys Cys His Cys Ser
35 40 45
Ala Asn Val Thr Ser Cys Leu Cys Leu Gly Ile Pro Ser Asp Asn Cys
50 55 60
Thr Arg Pro Cys Phe Ser Glu Arg Leu Ser Gln Met Thr Asn Thr Thr
65 70 75 80
Met Gln Thr Arg Tyr Pro Leu Ile Phe Ser Arg Val Lys Lys Ser Val
85 90 95
Glu Val Leu Lys Asn Asn Lys Cys Pro Tyr Phe Ser Cys Glu Gln Pro
100 105 110
Cys Asn Gln Thr Thr Ala Gly Asn Ala Leu Thr Phe Leu Lys Ser Leu
115 120 125
Leu Glu Ile Phe Gln Lys Glu Lys Met Arg Gly Met Arg Gly Lys Ile
130 135 140
<210> 100
<211> 189
<212> PRT
<213> 智人
<400> 100
Met Thr Glu Tyr Lys Leu Val Val Val Gly Ala Gly Gly Val Gly Lys
1 5 10 15
Ser Ala Leu Thr Ile Gln Leu Ile Gln Asn His Phe Val Asp Glu Tyr
20 25 30
Asp Pro Thr Ile Glu Asp Ser Tyr Arg Lys Gln Val Val Ile Asp Gly
35 40 45
Glu Thr Cys Leu Leu Asp Ile Leu Asp Thr Ala Gly Gln Glu Glu Tyr
50 55 60
Ser Ala Met Arg Asp Gln Tyr Met Arg Thr Gly Glu Gly Phe Leu Cys
65 70 75 80
Val Phe Ala Ile Asn Asn Thr Lys Ser Phe Glu Asp Ile His His Tyr
85 90 95
Arg Glu Gln Ile Lys Arg Val Lys Asp Ser Glu Asp Val Pro Met Val
100 105 110
Leu Val Gly Asn Lys Cys Asp Leu Pro Ser Arg Thr Val Asp Thr Lys
115 120 125
Gln Ala Gln Asp Leu Ala Arg Ser Tyr Gly Ile Pro Phe Ile Glu Thr
130 135 140
Ser Ala Lys Thr Arg Gln Arg Val Glu Asp Ala Phe Tyr Thr Leu Val
145 150 155 160
Arg Glu Ile Arg Gln Tyr Arg Leu Lys Lys Ile Ser Lys Glu Glu Lys
165 170 175
Thr Pro Gly Cys Val Lys Ile Lys Lys Cys Ile Ile Met
180 185
<210> 101
<211> 400
<212> PRT
<213> 智人
<400> 101
Met Thr Ser Tyr Ser Tyr Arg Gln Ser Ser Ala Thr Ser Ser Phe Gly
1 5 10 15
Gly Leu Gly Gly Gly Ser Val Arg Phe Gly Pro Gly Val Ala Phe Arg
20 25 30
Ala Pro Ser Ile His Gly Gly Ser Gly Gly Arg Gly Val Ser Val Ser
35 40 45
Ser Ala Arg Phe Val Ser Ser Ser Ser Ser Gly Ala Tyr Gly Gly Gly
50 55 60
Tyr Gly Gly Val Leu Thr Ala Ser Asp Gly Leu Leu Ala Gly Asn Glu
65 70 75 80
Lys Leu Thr Met Gln Asn Leu Asn Asp Arg Leu Ala Ser Tyr Leu Asp
85 90 95
Lys Val Arg Ala Leu Glu Ala Ala Asn Gly Glu Leu Glu Val Lys Ile
100 105 110
Arg Asp Trp Tyr Gln Lys Gln Gly Pro Gly Pro Ser Arg Asp Tyr Ser
115 120 125
His Tyr Tyr Thr Thr Ile Gln Asp Leu Arg Asp Lys Ile Leu Gly Ala
130 135 140
Thr Ile Glu Asn Ser Arg Ile Val Leu Gln Ile Asp Asn Ala Arg Leu
145 150 155 160
Ala Ala Asp Asp Phe Arg Thr Lys Phe Glu Thr Glu Gln Ala Leu Arg
165 170 175
Met Ser Val Glu Ala Asp Ile Asn Gly Leu Arg Arg Val Leu Asp Glu
180 185 190
Leu Thr Leu Ala Arg Thr Asp Leu Glu Met Gln Ile Glu Gly Leu Lys
195 200 205
Glu Glu Leu Ala Tyr Leu Lys Lys Asn His Glu Glu Glu Ile Ser Thr
210 215 220
Leu Arg Gly Gln Val Gly Gly Gln Val Ser Val Glu Val Asp Ser Ala
225 230 235 240
Pro Gly Thr Asp Leu Ala Lys Ile Leu Ser Asp Met Arg Ser Gln Tyr
245 250 255
Glu Val Met Ala Glu Gln Asn Arg Lys Asp Ala Glu Ala Trp Phe Thr
260 265 270
Ser Arg Thr Glu Glu Leu Asn Arg Glu Val Ala Gly His Thr Glu Gln
275 280 285
Leu Gln Met Ser Arg Ser Glu Val Thr Asp Leu Arg Arg Thr Leu Gln
290 295 300
Gly Leu Glu Ile Glu Leu Gln Ser Gln Leu Ser Met Lys Ala Ala Leu
305 310 315 320
Glu Asp Thr Leu Ala Glu Thr Glu Ala Arg Phe Gly Ala Gln Leu Ala
325 330 335
His Ile Gln Ala Leu Ile Ser Gly Ile Glu Ala Gln Leu Gly Asp Val
340 345 350
Arg Ala Asp Ser Glu Arg Gln Asn Gln Glu Tyr Gln Arg Leu Met Asp
355 360 365
Ile Lys Ser Arg Leu Glu Gln Glu Ile Ala Thr Tyr Arg Ser Leu Leu
370 375 380
Glu Gly Gln Glu Asp His Tyr Asn Asn Leu Ser Ala Ser Lys Val Leu
385 390 395 400
<210> 102
<211> 483
<212> PRT
<213> 智人
<400> 102
Met Ser Ile Arg Val Thr Gln Lys Ser Tyr Lys Val Ser Thr Ser Gly
1 5 10 15
Pro Arg Ala Phe Ser Ser Arg Ser Tyr Thr Ser Gly Pro Gly Ser Arg
20 25 30
Ile Ser Ser Ser Ser Phe Ser Arg Val Gly Ser Ser Asn Phe Arg Gly
35 40 45
Gly Leu Gly Gly Gly Tyr Gly Gly Ala Ser Gly Met Gly Gly Ile Thr
50 55 60
Ala Val Thr Val Asn Gln Ser Leu Leu Ser Pro Leu Val Leu Glu Val
65 70 75 80
Asp Pro Asn Ile Gln Ala Val Arg Thr Gln Glu Lys Glu Gln Ile Lys
85 90 95
Thr Leu Asn Asn Lys Phe Ala Ser Phe Ile Asp Lys Val Arg Phe Leu
100 105 110
Glu Gln Gln Asn Lys Met Leu Glu Thr Lys Trp Ser Leu Leu Gln Gln
115 120 125
Gln Lys Thr Ala Arg Ser Asn Met Asp Asn Met Phe Glu Ser Tyr Ile
130 135 140
Asn Asn Leu Arg Arg Gln Leu Glu Thr Leu Gly Gln Glu Lys Leu Lys
145 150 155 160
Leu Glu Ala Glu Leu Gly Asn Met Gln Gly Leu Val Glu Asp Phe Lys
165 170 175
Asn Lys Tyr Glu Asp Glu Ile Asn Lys Arg Thr Glu Met Glu Asn Glu
180 185 190
Phe Val Leu Ile Lys Lys Asp Val Asp Glu Ala Tyr Met Asn Lys Val
195 200 205
Glu Leu Glu Ser Arg Leu Glu Gly Leu Thr Asp Glu Ile Asn Phe Leu
210 215 220
Arg Gln Leu Tyr Glu Glu Glu Ile Arg Glu Leu Gln Ser Gln Ile Ser
225 230 235 240
Asp Thr Ser Val Val Leu Ser Met Asp Asn Ser Arg Ser Leu Asp Met
245 250 255
Asp Ser Ile Ile Ala Glu Val Lys Ala Gln Tyr Glu Asp Ile Ala Asn
260 265 270
Arg Ser Arg Ala Glu Ala Glu Ser Met Tyr Gln Ile Lys Tyr Glu Glu
275 280 285
Leu Gln Ser Leu Ala Gly Lys His Gly Asp Asp Leu Arg Arg Thr Lys
290 295 300
Thr Glu Ile Ser Glu Met Asn Arg Asn Ile Ser Arg Leu Gln Ala Glu
305 310 315 320
Ile Glu Gly Leu Lys Gly Gln Arg Ala Ser Leu Glu Ala Ala Ile Ala
325 330 335
Asp Ala Glu Gln Arg Gly Glu Leu Ala Ile Lys Asp Ala Asn Ala Lys
340 345 350
Leu Ser Glu Leu Glu Ala Ala Leu Gln Arg Ala Lys Gln Asp Met Ala
355 360 365
Arg Gln Leu Arg Glu Tyr Gln Glu Leu Met Asn Val Lys Leu Ala Leu
370 375 380
Asp Ile Glu Ile Ala Thr Tyr Arg Lys Leu Leu Glu Gly Glu Glu Ser
385 390 395 400
Arg Leu Glu Ser Gly Met Gln Asn Met Ser Ile His Thr Lys Thr Thr
405 410 415
Ser Gly Tyr Ala Gly Gly Leu Ser Ser Ala Tyr Gly Gly Leu Thr Ser
420 425 430
Pro Gly Leu Ser Tyr Ser Leu Gly Ser Ser Phe Gly Ser Gly Ala Gly
435 440 445
Ser Ser Ser Phe Ser Arg Thr Ser Ser Ser Arg Ala Val Val Val Lys
450 455 460
Lys Ile Glu Thr Arg Asp Gly Lys Leu Val Ser Glu Ser Ser Asp Val
465 470 475 480
Leu Pro Lys
<210> 103
<211> 3122
<212> PRT
<213> 智人
<400> 103
Met Pro Gly Ala Ala Gly Val Leu Leu Leu Leu Leu Leu Ser Gly Gly
1 5 10 15
Leu Gly Gly Val Gln Ala Gln Arg Pro Gln Gln Gln Arg Gln Ser Gln
20 25 30
Ala His Gln Gln Arg Gly Leu Phe Pro Ala Val Leu Asn Leu Ala Ser
35 40 45
Asn Ala Leu Ile Thr Thr Asn Ala Thr Cys Gly Glu Lys Gly Pro Glu
50 55 60
Met Tyr Cys Lys Leu Val Glu His Val Pro Gly Gln Pro Val Arg Asn
65 70 75 80
Pro Gln Cys Arg Ile Cys Asn Gln Asn Ser Ser Asn Pro Asn Gln Arg
85 90 95
His Pro Ile Thr Asn Ala Ile Asp Gly Lys Asn Thr Trp Trp Gln Ser
100 105 110
Pro Ser Ile Lys Asn Gly Ile Glu Tyr His Tyr Val Thr Ile Thr Leu
115 120 125
Asp Leu Gln Gln Val Phe Gln Ile Ala Tyr Val Ile Val Lys Ala Ala
130 135 140
Asn Ser Pro Arg Pro Gly Asn Trp Ile Leu Glu Arg Ser Leu Asp Asp
145 150 155 160
Val Glu Tyr Lys Pro Trp Gln Tyr His Ala Val Thr Asp Thr Glu Cys
165 170 175
Leu Thr Leu Tyr Asn Ile Tyr Pro Arg Thr Gly Pro Pro Ser Tyr Ala
180 185 190
Lys Asp Asp Glu Val Ile Cys Thr Ser Phe Tyr Ser Lys Ile His Pro
195 200 205
Leu Glu Asn Gly Glu Ile His Ile Ser Leu Ile Asn Gly Arg Pro Ser
210 215 220
Ala Asp Asp Pro Ser Pro Glu Leu Leu Glu Phe Thr Ser Ala Arg Tyr
225 230 235 240
Ile Arg Leu Arg Phe Gln Arg Ile Arg Thr Leu Asn Ala Asp Leu Met
245 250 255
Met Phe Ala His Lys Asp Pro Arg Glu Ile Asp Pro Ile Val Thr Arg
260 265 270
Arg Tyr Tyr Tyr Ser Val Lys Asp Ile Ser Val Gly Gly Met Cys Ile
275 280 285
Cys Tyr Gly His Ala Arg Ala Cys Pro Leu Asp Pro Ala Thr Asn Lys
290 295 300
Ser Arg Cys Glu Cys Glu His Asn Thr Cys Gly Asp Ser Cys Asp Gln
305 310 315 320
Cys Cys Pro Gly Phe His Gln Lys Pro Trp Arg Ala Gly Thr Phe Leu
325 330 335
Thr Lys Thr Glu Cys Glu Ala Cys Asn Cys His Gly Lys Ala Glu Glu
340 345 350
Cys Tyr Tyr Asp Glu Asn Val Ala Arg Arg Asn Leu Ser Leu Asn Ile
355 360 365
Arg Gly Lys Tyr Ile Gly Gly Gly Val Cys Ile Asn Cys Thr Gln Asn
370 375 380
Thr Ala Gly Ile Asn Cys Glu Thr Cys Thr Asp Gly Phe Phe Arg Pro
385 390 395 400
Lys Gly Val Ser Pro Asn Tyr Pro Arg Pro Cys Gln Pro Cys His Cys
405 410 415
Asp Pro Ile Gly Ser Leu Asn Glu Val Cys Val Lys Asp Glu Lys His
420 425 430
Ala Arg Arg Gly Leu Ala Pro Gly Ser Cys His Cys Lys Thr Gly Phe
435 440 445
Gly Gly Val Ser Cys Asp Arg Cys Ala Arg Gly Tyr Thr Gly Tyr Pro
450 455 460
Asp Cys Lys Ala Cys Asn Cys Ser Gly Leu Gly Ser Lys Asn Glu Asp
465 470 475 480
Pro Cys Phe Gly Pro Cys Ile Cys Lys Glu Asn Val Glu Gly Gly Asp
485 490 495
Cys Ser Arg Cys Lys Ser Gly Phe Phe Asn Leu Gln Glu Asp Asn Trp
500 505 510
Lys Gly Cys Asp Glu Cys Phe Cys Ser Gly Val Ser Asn Arg Cys Gln
515 520 525
Ser Ser Tyr Trp Thr Tyr Gly Lys Ile Gln Asp Met Ser Gly Trp Tyr
530 535 540
Leu Thr Asp Leu Pro Gly Arg Ile Arg Val Ala Pro Gln Gln Asp Asp
545 550 555 560
Leu Asp Ser Pro Gln Gln Ile Ser Ile Ser Asn Ala Glu Ala Arg Gln
565 570 575
Ala Leu Pro His Ser Tyr Tyr Trp Ser Ala Pro Ala Pro Tyr Leu Gly
580 585 590
Asn Lys Leu Pro Ala Val Gly Gly Gln Leu Thr Phe Thr Ile Ser Tyr
595 600 605
Asp Leu Glu Glu Glu Glu Glu Asp Thr Glu Arg Val Leu Gln Leu Met
610 615 620
Ile Ile Leu Glu Gly Asn Asp Leu Ser Ile Ser Thr Ala Gln Asp Glu
625 630 635 640
Val Tyr Leu His Pro Ser Glu Glu His Thr Asn Val Leu Leu Leu Lys
645 650 655
Glu Glu Ser Phe Thr Ile His Gly Thr His Phe Pro Val Arg Arg Lys
660 665 670
Glu Phe Met Thr Val Leu Ala Asn Leu Lys Arg Val Leu Leu Gln Ile
675 680 685
Thr Tyr Ser Phe Gly Met Asp Ala Ile Phe Arg Leu Ser Ser Val Asn
690 695 700
Leu Glu Ser Ala Val Ser Tyr Pro Thr Asp Gly Ser Ile Ala Ala Ala
705 710 715 720
Val Glu Val Cys Gln Cys Pro Pro Gly Tyr Thr Gly Ser Ser Cys Glu
725 730 735
Ser Cys Trp Pro Arg His Arg Arg Val Asn Gly Thr Ile Phe Gly Gly
740 745 750
Ile Cys Glu Pro Cys Gln Cys Phe Gly His Ala Glu Ser Cys Asp Asp
755 760 765
Val Thr Gly Glu Cys Leu Asn Cys Lys Asp His Thr Gly Gly Pro Tyr
770 775 780
Cys Asp Lys Cys Leu Pro Gly Phe Tyr Gly Glu Pro Thr Lys Gly Thr
785 790 795 800
Ser Glu Asp Cys Gln Pro Cys Ala Cys Pro Leu Asn Ile Pro Ser Asn
805 810 815
Asn Phe Ser Pro Thr Cys His Leu Asp Arg Ser Leu Gly Leu Ile Cys
820 825 830
Asp Gly Cys Pro Val Gly Tyr Thr Gly Pro Arg Cys Glu Arg Cys Ala
835 840 845
Glu Gly Tyr Phe Gly Gln Pro Ser Val Pro Gly Gly Ser Cys Gln Pro
850 855 860
Cys Gln Cys Asn Asp Asn Leu Asp Phe Ser Ile Pro Gly Ser Cys Asp
865 870 875 880
Ser Leu Ser Gly Ser Cys Leu Ile Cys Lys Pro Gly Thr Thr Gly Arg
885 890 895
Tyr Cys Glu Leu Cys Ala Asp Gly Tyr Phe Gly Asp Ala Val Asp Ala
900 905 910
Lys Asn Cys Gln Pro Cys Arg Cys Asn Ala Gly Gly Ser Phe Ser Glu
915 920 925
Val Cys His Ser Gln Thr Gly Gln Cys Glu Cys Arg Ala Asn Val Gln
930 935 940
Gly Gln Arg Cys Asp Lys Cys Lys Ala Gly Thr Phe Gly Leu Gln Ser
945 950 955 960
Ala Arg Gly Cys Val Pro Cys Asn Cys Asn Ser Phe Gly Ser Lys Ser
965 970 975
Phe Asp Cys Glu Glu Ser Gly Gln Cys Trp Cys Gln Pro Gly Val Thr
980 985 990
Gly Lys Lys Cys Asp Arg Cys Ala His Gly Tyr Phe Asn Phe Gln Glu
995 1000 1005
Gly Gly Cys Thr Ala Cys Glu Cys Ser His Leu Gly Asn Asn Cys
1010 1015 1020
Asp Pro Lys Thr Gly Arg Cys Ile Cys Pro Pro Asn Thr Ile Gly
1025 1030 1035
Glu Lys Cys Ser Lys Cys Ala Pro Asn Thr Trp Gly His Ser Ile
1040 1045 1050
Thr Thr Gly Cys Lys Ala Cys Asn Cys Ser Thr Val Gly Ser Leu
1055 1060 1065
Asp Phe Gln Cys Asn Val Asn Thr Gly Gln Cys Asn Cys His Pro
1070 1075 1080
Lys Phe Ser Gly Ala Lys Cys Thr Glu Cys Ser Arg Gly His Trp
1085 1090 1095
Asn Tyr Pro Arg Cys Asn Leu Cys Asp Cys Phe Leu Pro Gly Thr
1100 1105 1110
Asp Ala Thr Thr Cys Asp Ser Glu Thr Lys Lys Cys Ser Cys Ser
1115 1120 1125
Asp Gln Thr Gly Gln Cys Thr Cys Lys Val Asn Val Glu Gly Ile
1130 1135 1140
His Cys Asp Arg Cys Arg Pro Gly Lys Phe Gly Leu Asp Ala Lys
1145 1150 1155
Asn Pro Leu Gly Cys Ser Ser Cys Tyr Cys Phe Gly Thr Thr Thr
1160 1165 1170
Gln Cys Ser Glu Ala Lys Gly Leu Ile Arg Thr Trp Val Thr Leu
1175 1180 1185
Lys Ala Glu Gln Thr Ile Leu Pro Leu Val Asp Glu Ala Leu Gln
1190 1195 1200
His Thr Thr Thr Lys Gly Ile Val Phe Gln His Pro Glu Ile Val
1205 1210 1215
Ala His Met Asp Leu Met Arg Glu Asp Leu His Leu Glu Pro Phe
1220 1225 1230
Tyr Trp Lys Leu Pro Glu Gln Phe Glu Gly Lys Lys Leu Met Ala
1235 1240 1245
Tyr Gly Gly Lys Leu Lys Tyr Ala Ile Tyr Phe Glu Ala Arg Glu
1250 1255 1260
Glu Thr Gly Phe Ser Thr Tyr Asn Pro Gln Val Ile Ile Arg Gly
1265 1270 1275
Gly Thr Pro Thr His Ala Arg Ile Ile Val Arg His Met Ala Ala
1280 1285 1290
Pro Leu Ile Gly Gln Leu Thr Arg His Glu Ile Glu Met Thr Glu
1295 1300 1305
Lys Glu Trp Lys Tyr Tyr Gly Asp Asp Pro Arg Val His Arg Thr
1310 1315 1320
Val Thr Arg Glu Asp Phe Leu Asp Ile Leu Tyr Asp Ile His Tyr
1325 1330 1335
Ile Leu Ile Lys Ala Thr Tyr Gly Asn Phe Met Arg Gln Ser Arg
1340 1345 1350
Ile Ser Glu Ile Ser Met Glu Val Ala Glu Gln Gly Arg Gly Thr
1355 1360 1365
Thr Met Thr Pro Pro Ala Asp Leu Ile Glu Lys Cys Asp Cys Pro
1370 1375 1380
Leu Gly Tyr Ser Gly Leu Ser Cys Glu Ala Cys Leu Pro Gly Phe
1385 1390 1395
Tyr Arg Leu Arg Ser Gln Pro Gly Gly Arg Thr Pro Gly Pro Thr
1400 1405 1410
Leu Gly Thr Cys Val Pro Cys Gln Cys Asn Gly His Ser Ser Leu
1415 1420 1425
Cys Asp Pro Glu Thr Ser Ile Cys Gln Asn Cys Gln His His Thr
1430 1435 1440
Ala Gly Asp Phe Cys Glu Arg Cys Ala Leu Gly Tyr Tyr Gly Ile
1445 1450 1455
Val Lys Gly Leu Pro Asn Asp Cys Gln Gln Cys Ala Cys Pro Leu
1460 1465 1470
Ile Ser Ser Ser Asn Asn Phe Ser Pro Ser Cys Val Ala Glu Gly
1475 1480 1485
Leu Asp Asp Tyr Arg Cys Thr Ala Cys Pro Arg Gly Tyr Glu Gly
1490 1495 1500
Gln Tyr Cys Glu Arg Cys Ala Pro Gly Tyr Thr Gly Ser Pro Gly
1505 1510 1515
Asn Pro Gly Gly Ser Cys Gln Glu Cys Glu Cys Asp Pro Tyr Gly
1520 1525 1530
Ser Leu Pro Val Pro Cys Asp Pro Val Thr Gly Phe Cys Thr Cys
1535 1540 1545
Arg Pro Gly Ala Thr Gly Arg Lys Cys Asp Gly Cys Lys His Trp
1550 1555 1560
His Ala Arg Glu Gly Trp Glu Cys Val Phe Cys Gly Asp Glu Cys
1565 1570 1575
Thr Gly Leu Leu Leu Gly Asp Leu Ala Arg Leu Glu Gln Met Val
1580 1585 1590
Met Ser Ile Asn Leu Thr Gly Pro Leu Pro Ala Pro Tyr Lys Met
1595 1600 1605
Leu Tyr Gly Leu Glu Asn Met Thr Gln Glu Leu Lys His Leu Leu
1610 1615 1620
Ser Pro Gln Arg Ala Pro Glu Arg Leu Ile Gln Leu Ala Glu Gly
1625 1630 1635
Asn Leu Asn Thr Leu Val Thr Glu Met Asn Glu Leu Leu Thr Arg
1640 1645 1650
Ala Thr Lys Val Thr Ala Asp Gly Glu Gln Thr Gly Gln Asp Ala
1655 1660 1665
Glu Arg Thr Asn Thr Arg Ala Lys Ser Leu Gly Glu Phe Ile Lys
1670 1675 1680
Glu Leu Ala Arg Asp Ala Glu Ala Val Asn Glu Lys Ala Ile Lys
1685 1690 1695
Leu Asn Glu Thr Leu Gly Thr Arg Asp Glu Ala Phe Glu Arg Asn
1700 1705 1710
Leu Glu Gly Leu Gln Lys Glu Ile Asp Gln Met Ile Lys Glu Leu
1715 1720 1725
Arg Arg Lys Asn Leu Glu Thr Gln Lys Glu Ile Ala Glu Asp Glu
1730 1735 1740
Leu Val Ala Ala Glu Ala Leu Leu Lys Lys Val Lys Lys Leu Phe
1745 1750 1755
Gly Glu Ser Arg Gly Glu Asn Glu Glu Met Glu Lys Asp Leu Arg
1760 1765 1770
Glu Lys Leu Ala Asp Tyr Lys Asn Lys Val Asp Asp Ala Trp Asp
1775 1780 1785
Leu Leu Arg Glu Ala Thr Asp Lys Ile Arg Glu Ala Asn Arg Leu
1790 1795 1800
Phe Ala Val Asn Gln Lys Asn Met Thr Ala Leu Glu Lys Lys Lys
1805 1810 1815
Glu Ala Val Glu Ser Gly Lys Arg Gln Ile Glu Asn Thr Leu Lys
1820 1825 1830
Glu Gly Asn Asp Ile Leu Asp Glu Ala Asn Arg Leu Ala Asp Glu
1835 1840 1845
Ile Asn Ser Ile Ile Asp Tyr Val Glu Asp Ile Gln Thr Lys Leu
1850 1855 1860
Pro Pro Met Ser Glu Glu Leu Asn Asp Lys Ile Asp Asp Leu Ser
1865 1870 1875
Gln Glu Ile Lys Asp Arg Lys Leu Ala Glu Lys Val Ser Gln Ala
1880 1885 1890
Glu Ser His Ala Ala Gln Leu Asn Asp Ser Ser Ala Val Leu Asp
1895 1900 1905
Gly Ile Leu Asp Glu Ala Lys Asn Ile Ser Phe Asn Ala Thr Ala
1910 1915 1920
Ala Phe Lys Ala Tyr Ser Asn Ile Lys Asp Tyr Ile Asp Glu Ala
1925 1930 1935
Glu Lys Val Ala Lys Glu Ala Lys Asp Leu Ala His Glu Ala Thr
1940 1945 1950
Lys Leu Ala Thr Gly Pro Arg Gly Leu Leu Lys Glu Asp Ala Lys
1955 1960 1965
Gly Cys Leu Gln Lys Ser Phe Arg Ile Leu Asn Glu Ala Lys Lys
1970 1975 1980
Leu Ala Asn Asp Val Lys Glu Asn Glu Asp His Leu Asn Gly Leu
1985 1990 1995
Lys Thr Arg Ile Glu Asn Ala Asp Ala Arg Asn Gly Asp Leu Leu
2000 2005 2010
Arg Thr Leu Asn Asp Thr Leu Gly Lys Leu Ser Ala Ile Pro Asn
2015 2020 2025
Asp Thr Ala Ala Lys Leu Gln Ala Val Lys Asp Lys Ala Arg Gln
2030 2035 2040
Ala Asn Asp Thr Ala Lys Asp Val Leu Ala Gln Ile Thr Glu Leu
2045 2050 2055
His Gln Asn Leu Asp Gly Leu Lys Lys Asn Tyr Asn Lys Leu Ala
2060 2065 2070
Asp Ser Val Ala Lys Thr Asn Ala Val Val Lys Asp Pro Ser Lys
2075 2080 2085
Asn Lys Ile Ile Ala Asp Ala Asp Ala Thr Val Lys Asn Leu Glu
2090 2095 2100
Gln Glu Ala Asp Arg Leu Ile Asp Lys Leu Lys Pro Ile Lys Glu
2105 2110 2115
Leu Glu Asp Asn Leu Lys Lys Asn Ile Ser Glu Ile Lys Glu Leu
2120 2125 2130
Ile Asn Gln Ala Arg Lys Gln Ala Asn Ser Ile Lys Val Ser Val
2135 2140 2145
Ser Ser Gly Gly Asp Cys Ile Arg Thr Tyr Lys Pro Glu Ile Lys
2150 2155 2160
Lys Gly Ser Tyr Asn Asn Ile Val Val Asn Val Lys Thr Ala Val
2165 2170 2175
Ala Asp Asn Leu Leu Phe Tyr Leu Gly Ser Ala Lys Phe Ile Asp
2180 2185 2190
Phe Leu Ala Ile Glu Met Arg Lys Gly Lys Val Ser Phe Leu Trp
2195 2200 2205
Asp Val Gly Ser Gly Val Gly Arg Val Glu Tyr Pro Asp Leu Thr
2210 2215 2220
Ile Asp Asp Ser Tyr Trp Tyr Arg Ile Val Ala Ser Arg Thr Gly
2225 2230 2235
Arg Asn Gly Thr Ile Ser Val Arg Ala Leu Asp Gly Pro Lys Ala
2240 2245 2250
Ser Ile Val Pro Ser Thr His His Ser Thr Ser Pro Pro Gly Tyr
2255 2260 2265
Thr Ile Leu Asp Val Asp Ala Asn Ala Met Leu Phe Val Gly Gly
2270 2275 2280
Leu Thr Gly Lys Leu Lys Lys Ala Asp Ala Val Arg Val Ile Thr
2285 2290 2295
Phe Thr Gly Cys Met Gly Glu Thr Tyr Phe Asp Asn Lys Pro Ile
2300 2305 2310
Gly Leu Trp Asn Phe Arg Glu Lys Glu Gly Asp Cys Lys Gly Cys
2315 2320 2325
Thr Val Ser Pro Gln Val Glu Asp Ser Glu Gly Thr Ile Gln Phe
2330 2335 2340
Asp Gly Glu Gly Tyr Ala Leu Val Ser Arg Pro Ile Arg Trp Tyr
2345 2350 2355
Pro Asn Ile Ser Thr Val Met Phe Lys Phe Arg Thr Phe Ser Ser
2360 2365 2370
Ser Ala Leu Leu Met Tyr Leu Ala Thr Arg Asp Leu Arg Asp Phe
2375 2380 2385
Met Ser Val Glu Leu Thr Asp Gly His Ile Lys Val Ser Tyr Asp
2390 2395 2400
Leu Gly Ser Gly Met Ala Ser Val Val Ser Asn Gln Asn His Asn
2405 2410 2415
Asp Gly Lys Trp Lys Ser Phe Thr Leu Ser Arg Ile Gln Lys Gln
2420 2425 2430
Ala Asn Ile Ser Ile Val Asp Ile Asp Thr Asn Gln Glu Glu Asn
2435 2440 2445
Ile Ala Thr Ser Ser Ser Gly Asn Asn Phe Gly Leu Asp Leu Lys
2450 2455 2460
Ala Asp Asp Lys Ile Tyr Phe Gly Gly Leu Pro Thr Leu Arg Asn
2465 2470 2475
Leu Ser Met Lys Ala Arg Pro Glu Val Asn Leu Lys Lys Tyr Ser
2480 2485 2490
Gly Cys Leu Lys Asp Ile Glu Ile Ser Arg Thr Pro Tyr Asn Ile
2495 2500 2505
Leu Ser Ser Pro Asp Tyr Val Gly Val Thr Lys Gly Cys Ser Leu
2510 2515 2520
Glu Asn Val Tyr Thr Val Ser Phe Pro Lys Pro Gly Phe Val Glu
2525 2530 2535
Leu Ser Pro Val Pro Ile Asp Val Gly Thr Glu Ile Asn Leu Ser
2540 2545 2550
Phe Ser Thr Lys Asn Glu Ser Gly Ile Ile Leu Leu Gly Ser Gly
2555 2560 2565
Gly Thr Pro Ala Pro Pro Arg Arg Lys Arg Arg Gln Thr Gly Gln
2570 2575 2580
Ala Tyr Tyr Ala Ile Leu Leu Asn Arg Gly Arg Leu Glu Val His
2585 2590 2595
Leu Ser Thr Gly Ala Arg Thr Met Arg Lys Ile Val Ile Arg Pro
2600 2605 2610
Glu Pro Asn Leu Phe His Asp Gly Arg Glu His Ser Val His Val
2615 2620 2625
Glu Arg Thr Arg Gly Ile Phe Thr Val Gln Val Asp Glu Asn Arg
2630 2635 2640
Arg Tyr Met Gln Asn Leu Thr Val Glu Gln Pro Ile Glu Val Lys
2645 2650 2655
Lys Leu Phe Val Gly Gly Ala Pro Pro Glu Phe Gln Pro Ser Pro
2660 2665 2670
Leu Arg Asn Ile Pro Pro Phe Glu Gly Cys Ile Trp Asn Leu Val
2675 2680 2685
Ile Asn Ser Val Pro Met Asp Phe Ala Arg Pro Val Ser Phe Lys
2690 2695 2700
Asn Ala Asp Ile Gly Arg Cys Ala His Gln Lys Leu Arg Glu Asp
2705 2710 2715
Glu Asp Gly Ala Ala Pro Ala Glu Ile Val Ile Gln Pro Glu Pro
2720 2725 2730
Val Pro Thr Pro Ala Phe Pro Thr Pro Thr Pro Val Leu Thr His
2735 2740 2745
Gly Pro Cys Ala Ala Glu Ser Glu Pro Ala Leu Leu Ile Gly Ser
2750 2755 2760
Lys Gln Phe Gly Leu Ser Arg Asn Ser His Ile Ala Ile Ala Phe
2765 2770 2775
Asp Asp Thr Lys Val Lys Asn Arg Leu Thr Ile Glu Leu Glu Val
2780 2785 2790
Arg Thr Glu Ala Glu Ser Gly Leu Leu Phe Tyr Met Ala Arg Ile
2795 2800 2805
Asn His Ala Asp Phe Ala Thr Val Gln Leu Arg Asn Gly Leu Pro
2810 2815 2820
Tyr Phe Ser Tyr Asp Leu Gly Ser Gly Asp Thr His Thr Met Ile
2825 2830 2835
Pro Thr Lys Ile Asn Asp Gly Gln Trp His Lys Ile Lys Ile Met
2840 2845 2850
Arg Ser Lys Gln Glu Gly Ile Leu Tyr Val Asp Gly Ala Ser Asn
2855 2860 2865
Arg Thr Ile Ser Pro Lys Lys Ala Asp Ile Leu Asp Val Val Gly
2870 2875 2880
Met Leu Tyr Val Gly Gly Leu Pro Ile Asn Tyr Thr Thr Arg Arg
2885 2890 2895
Ile Gly Pro Val Thr Tyr Ser Ile Asp Gly Cys Val Arg Asn Leu
2900 2905 2910
His Met Ala Glu Ala Pro Ala Asp Leu Glu Gln Pro Thr Ser Ser
2915 2920 2925
Phe His Val Gly Thr Cys Phe Ala Asn Ala Gln Arg Gly Thr Tyr
2930 2935 2940
Phe Asp Gly Thr Gly Phe Ala Lys Ala Val Gly Gly Phe Lys Val
2945 2950 2955
Gly Leu Asp Leu Leu Val Glu Phe Glu Phe Arg Thr Thr Thr Thr
2960 2965 2970
Thr Gly Val Leu Leu Gly Ile Ser Ser Gln Lys Met Asp Gly Met
2975 2980 2985
Gly Ile Glu Met Ile Asp Glu Lys Leu Met Phe His Val Asp Asn
2990 2995 3000
Gly Ala Gly Arg Phe Thr Ala Val Tyr Asp Ala Gly Val Pro Gly
3005 3010 3015
His Leu Cys Asp Gly Gln Trp His Lys Val Thr Ala Asn Lys Ile
3020 3025 3030
Lys His Arg Ile Glu Leu Thr Val Asp Gly Asn Gln Val Glu Ala
3035 3040 3045
Gln Ser Pro Asn Pro Ala Ser Thr Ser Ala Asp Thr Asn Asp Pro
3050 3055 3060
Val Phe Val Gly Gly Phe Pro Asp Asp Leu Lys Gln Phe Gly Leu
3065 3070 3075
Thr Thr Ser Ile Pro Phe Arg Gly Cys Ile Arg Ser Leu Lys Leu
3080 3085 3090
Thr Lys Gly Thr Gly Lys Pro Leu Glu Val Asn Phe Ala Lys Ala
3095 3100 3105
Leu Glu Leu Arg Gly Val Gln Pro Val Ser Cys Pro Ala Asn
3110 3115 3120
<210> 104
<211> 250
<212> PRT
<213> 智人
<400> 104
Met Ala Asp Asn Phe Ser Leu His Asp Ala Leu Ser Gly Ser Gly Asn
1 5 10 15
Pro Asn Pro Gln Gly Trp Pro Gly Ala Trp Gly Asn Gln Pro Ala Gly
20 25 30
Ala Gly Gly Tyr Pro Gly Ala Ser Tyr Pro Gly Ala Tyr Pro Gly Gln
35 40 45
Ala Pro Pro Gly Ala Tyr Pro Gly Gln Ala Pro Pro Gly Ala Tyr Pro
50 55 60
Gly Ala Pro Gly Ala Tyr Pro Gly Ala Pro Ala Pro Gly Val Tyr Pro
65 70 75 80
Gly Pro Pro Ser Gly Pro Gly Ala Tyr Pro Ser Ser Gly Gln Pro Ser
85 90 95
Ala Thr Gly Ala Tyr Pro Ala Thr Gly Pro Tyr Gly Ala Pro Ala Gly
100 105 110
Pro Leu Ile Val Pro Tyr Asn Leu Pro Leu Pro Gly Gly Val Val Pro
115 120 125
Arg Met Leu Ile Thr Ile Leu Gly Thr Val Lys Pro Asn Ala Asn Arg
130 135 140
Ile Ala Leu Asp Phe Gln Arg Gly Asn Asp Val Ala Phe His Phe Asn
145 150 155 160
Pro Arg Phe Asn Glu Asn Asn Arg Arg Val Ile Val Cys Asn Thr Lys
165 170 175
Leu Asp Asn Asn Trp Gly Arg Glu Glu Arg Gln Ser Val Phe Pro Phe
180 185 190
Glu Ser Gly Lys Pro Phe Lys Ile Gln Val Leu Val Glu Pro Asp His
195 200 205
Phe Lys Val Ala Val Asn Asp Ala His Leu Leu Gln Tyr Asn His Arg
210 215 220
Val Lys Lys Leu Asn Glu Ile Ser Lys Leu Gly Ile Ser Gly Asp Ile
225 230 235 240
Asp Leu Thr Ser Ala Ser Tyr Thr Met Ile
245 250
<210> 105
<211> 586
<212> PRT
<213> 智人
<400> 105
Met Ala Thr Ala Thr Pro Val Pro Pro Arg Met Gly Ser Arg Ala Gly
1 5 10 15
Gly Pro Thr Thr Pro Leu Ser Pro Thr Arg Leu Ser Arg Leu Gln Glu
20 25 30
Lys Glu Glu Leu Arg Glu Leu Asn Asp Arg Leu Ala Val Tyr Ile Asp
35 40 45
Lys Val Arg Ser Leu Glu Thr Glu Asn Ser Ala Leu Gln Leu Gln Val
50 55 60
Thr Glu Arg Glu Glu Val Arg Gly Arg Glu Leu Thr Gly Leu Lys Ala
65 70 75 80
Leu Tyr Glu Thr Glu Leu Ala Asp Ala Arg Arg Ala Leu Asp Asp Thr
85 90 95
Ala Arg Glu Arg Ala Lys Leu Gln Ile Glu Leu Gly Lys Cys Lys Ala
100 105 110
Glu His Asp Gln Leu Leu Leu Asn Tyr Ala Lys Lys Glu Ser Asp Leu
115 120 125
Asn Gly Ala Gln Ile Lys Leu Arg Glu Tyr Glu Ala Ala Leu Asn Ser
130 135 140
Lys Asp Ala Ala Leu Ala Thr Ala Leu Gly Asp Lys Lys Ser Leu Glu
145 150 155 160
Gly Asp Leu Glu Asp Leu Lys Asp Gln Ile Ala Gln Leu Glu Ala Ser
165 170 175
Leu Ala Ala Ala Lys Lys Gln Leu Ala Asp Glu Thr Leu Leu Lys Val
180 185 190
Asp Leu Glu Asn Arg Cys Gln Ser Leu Thr Glu Asp Leu Glu Phe Arg
195 200 205
Lys Ser Met Tyr Glu Glu Glu Ile Asn Glu Thr Arg Arg Lys His Glu
210 215 220
Thr Arg Leu Val Glu Val Asp Ser Gly Arg Gln Ile Glu Tyr Glu Tyr
225 230 235 240
Lys Leu Ala Gln Ala Leu His Glu Met Arg Glu Gln His Asp Ala Gln
245 250 255
Val Arg Leu Tyr Lys Glu Glu Leu Glu Gln Thr Tyr His Ala Lys Leu
260 265 270
Glu Asn Ala Arg Leu Ser Ser Glu Met Asn Thr Ser Thr Val Asn Ser
275 280 285
Ala Arg Glu Glu Leu Met Glu Ser Arg Met Arg Ile Glu Ser Leu Ser
290 295 300
Ser Gln Leu Ser Asn Leu Gln Lys Glu Ser Arg Ala Cys Leu Glu Arg
305 310 315 320
Ile Gln Glu Leu Glu Asp Leu Leu Ala Lys Glu Lys Asp Asn Ser Arg
325 330 335
Arg Met Leu Thr Asp Lys Glu Arg Glu Met Ala Glu Ile Arg Asp Gln
340 345 350
Met Gln Gln Gln Leu Asn Asp Tyr Glu Gln Leu Leu Asp Val Lys Leu
355 360 365
Ala Leu Asp Met Glu Ile Ser Ala Tyr Arg Lys Leu Leu Glu Gly Glu
370 375 380
Glu Glu Arg Leu Lys Leu Ser Pro Ser Pro Ser Ser Arg Val Thr Val
385 390 395 400
Ser Arg Ala Ser Ser Ser Arg Ser Val Arg Thr Thr Arg Gly Lys Arg
405 410 415
Lys Arg Val Asp Val Glu Glu Ser Glu Ala Ser Ser Ser Val Ser Ile
420 425 430
Ser His Ser Ala Ser Ala Thr Gly Asn Val Cys Ile Glu Glu Ile Asp
435 440 445
Val Asp Gly Lys Phe Ile Arg Leu Lys Asn Thr Ser Glu Gln Asp Gln
450 455 460
Pro Met Gly Gly Trp Glu Met Ile Arg Lys Ile Gly Asp Thr Ser Val
465 470 475 480
Ser Tyr Lys Tyr Thr Ser Arg Tyr Val Leu Lys Ala Gly Gln Thr Val
485 490 495
Thr Ile Trp Ala Ala Asn Ala Gly Val Thr Ala Ser Pro Pro Thr Asp
500 505 510
Leu Ile Trp Lys Asn Gln Asn Ser Trp Gly Thr Gly Glu Asp Val Lys
515 520 525
Val Ile Leu Lys Asn Ser Gln Gly Glu Glu Val Ala Gln Arg Ser Thr
530 535 540
Val Phe Lys Thr Thr Ile Pro Glu Glu Glu Glu Glu Glu Glu Glu Ala
545 550 555 560
Ala Gly Val Val Val Glu Glu Glu Leu Phe His Gln Gln Gly Thr Pro
565 570 575
Arg Ala Ser Asn Arg Ser Cys Ala Ile Met
580 585
<210> 106
<211> 268
<212> PRT
<213> 智人
<400> 106
Met Ala Val Asn Val Tyr Ser Thr Ser Val Thr Ser Asp Asn Leu Ser
1 5 10 15
Arg His Asp Met Leu Ala Trp Ile Asn Glu Ser Leu Gln Leu Asn Leu
20 25 30
Thr Lys Ile Glu Gln Leu Cys Ser Gly Ala Ala Tyr Cys Gln Phe Met
35 40 45
Asp Met Leu Phe Pro Gly Ser Ile Ala Leu Lys Lys Val Lys Phe Gln
50 55 60
Ala Lys Leu Glu His Glu Tyr Ile Gln Asn Phe Lys Ile Leu Gln Ala
65 70 75 80
Gly Phe Lys Arg Met Gly Val Asp Lys Ile Ile Pro Val Asp Lys Leu
85 90 95
Val Lys Gly Lys Phe Gln Asp Asn Phe Glu Phe Val Gln Trp Phe Lys
100 105 110
Lys Phe Phe Asp Ala Asn Tyr Asp Gly Lys Asp Tyr Asp Pro Val Ala
115 120 125
Ala Arg Gln Gly Gln Glu Thr Ala Val Ala Pro Ser Leu Val Ala Pro
130 135 140
Ala Leu Asn Lys Pro Lys Lys Pro Leu Thr Ser Ser Ser Ala Ala Pro
145 150 155 160
Gln Arg Pro Ile Ser Thr Gln Arg Thr Ala Ala Ala Pro Lys Ala Gly
165 170 175
Pro Gly Val Val Arg Lys Asn Pro Gly Val Gly Asn Gly Asp Asp Glu
180 185 190
Ala Ala Glu Leu Met Gln Gln Val Asn Val Leu Lys Leu Thr Val Glu
195 200 205
Asp Leu Glu Lys Glu Arg Asp Phe Tyr Phe Gly Lys Leu Arg Asn Ile
210 215 220
Glu Leu Ile Cys Gln Glu Asn Glu Gly Glu Asn Asp Pro Val Leu Gln
225 230 235 240
Arg Ile Val Asp Ile Leu Tyr Ala Thr Asp Glu Gly Phe Val Ile Pro
245 250 255
Asp Glu Gly Gly Pro Gln Glu Glu Gln Glu Glu Tyr
260 265
<210> 107
<211> 863
<212> PRT
<213> 智人
<400> 107
Met Ser Ser Pro Ala Ser Thr Pro Ser Arg Arg Gly Ser Arg Arg Gly
1 5 10 15
Arg Ala Thr Pro Ala Gln Thr Pro Arg Ser Glu Asp Ala Arg Ser Ser
20 25 30
Pro Ser Gln Arg Arg Arg Gly Glu Asp Ser Thr Ser Thr Gly Glu Leu
35 40 45
Gln Pro Met Pro Thr Ser Pro Gly Val Asp Leu Gln Ser Pro Ala Ala
50 55 60
Gln Asp Val Leu Phe Ser Ser Pro Pro Gln Met His Ser Ser Ala Ile
65 70 75 80
Pro Leu Asp Phe Asp Val Ser Ser Pro Leu Thr Tyr Gly Thr Pro Ser
85 90 95
Ser Arg Val Glu Gly Thr Pro Arg Ser Gly Val Arg Gly Thr Pro Val
100 105 110
Arg Gln Arg Pro Asp Leu Gly Ser Ala Gln Lys Gly Leu Gln Val Asp
115 120 125
Leu Gln Ser Asp Gly Ala Ala Ala Glu Asp Ile Val Ala Ser Glu Gln
130 135 140
Ser Leu Gly Gln Lys Leu Val Ile Trp Gly Thr Asp Val Asn Val Ala
145 150 155 160
Ala Cys Lys Glu Asn Phe Gln Arg Phe Leu Gln Arg Phe Ile Asp Pro
165 170 175
Leu Ala Lys Glu Glu Glu Asn Val Gly Ile Asp Ile Thr Glu Pro Leu
180 185 190
Tyr Met Gln Arg Leu Gly Glu Ile Asn Val Ile Gly Glu Pro Phe Leu
195 200 205
Asn Val Asn Cys Glu His Ile Lys Ser Phe Asp Lys Asn Leu Tyr Arg
210 215 220
Gln Leu Ile Ser Tyr Pro Gln Glu Val Ile Pro Thr Phe Asp Met Ala
225 230 235 240
Val Asn Glu Ile Phe Phe Asp Arg Tyr Pro Asp Ser Ile Leu Glu His
245 250 255
Gln Ile Gln Val Arg Pro Phe Asn Ala Leu Lys Thr Lys Asn Met Arg
260 265 270
Asn Leu Asn Pro Glu Asp Ile Asp Gln Leu Ile Thr Ile Ser Gly Met
275 280 285
Val Ile Arg Thr Ser Gln Leu Ile Pro Glu Met Gln Glu Ala Phe Phe
290 295 300
Gln Cys Gln Val Cys Ala His Thr Thr Arg Val Glu Met Asp Arg Gly
305 310 315 320
Arg Ile Ala Glu Pro Ser Val Cys Gly Arg Cys His Thr Thr His Ser
325 330 335
Met Ala Leu Ile His Asn Arg Ser Leu Phe Ser Asp Lys Gln Met Ile
340 345 350
Lys Leu Gln Glu Ser Pro Glu Asp Met Pro Ala Gly Gln Thr Pro His
355 360 365
Thr Val Ile Leu Phe Ala His Asn Asp Leu Val Asp Lys Val Gln Pro
370 375 380
Gly Asp Arg Val Asn Val Thr Gly Ile Tyr Arg Ala Val Pro Ile Arg
385 390 395 400
Val Asn Pro Arg Val Ser Asn Val Lys Ser Val Tyr Lys Thr His Ile
405 410 415
Asp Val Ile His Tyr Arg Lys Thr Asp Ala Lys Arg Leu His Gly Leu
420 425 430
Asp Glu Glu Ala Glu Gln Lys Leu Phe Ser Glu Lys Arg Val Glu Leu
435 440 445
Leu Lys Glu Leu Ser Arg Lys Pro Asp Ile Tyr Glu Arg Leu Ala Ser
450 455 460
Ala Leu Ala Pro Ser Ile Tyr Glu His Glu Asp Ile Lys Lys Gly Ile
465 470 475 480
Leu Leu Gln Leu Phe Gly Gly Thr Arg Lys Asp Phe Ser His Thr Gly
485 490 495
Arg Gly Lys Phe Arg Ala Glu Ile Asn Ile Leu Leu Cys Gly Asp Pro
500 505 510
Gly Thr Ser Lys Ser Gln Leu Leu Gln Tyr Val Tyr Asn Leu Val Pro
515 520 525
Arg Gly Gln Tyr Thr Ser Gly Lys Gly Ser Ser Ala Val Gly Leu Thr
530 535 540
Ala Tyr Val Met Lys Asp Pro Glu Thr Arg Gln Leu Val Leu Gln Thr
545 550 555 560
Gly Ala Leu Val Leu Ser Asp Asn Gly Ile Cys Cys Ile Asp Glu Phe
565 570 575
Asp Lys Met Asn Glu Ser Thr Arg Ser Val Leu His Glu Val Met Glu
580 585 590
Gln Gln Thr Leu Ser Ile Ala Lys Ala Gly Ile Ile Cys Gln Leu Asn
595 600 605
Ala Arg Thr Ser Val Leu Ala Ala Ala Asn Pro Ile Glu Ser Gln Trp
610 615 620
Asn Pro Lys Lys Thr Thr Ile Glu Asn Ile Gln Leu Pro His Thr Leu
625 630 635 640
Leu Ser Arg Phe Asp Leu Ile Phe Leu Leu Leu Asp Pro Gln Asp Glu
645 650 655
Ala Tyr Asp Arg Arg Leu Ala His His Leu Val Ala Leu Tyr Tyr Gln
660 665 670
Ser Glu Glu Gln Ala Glu Glu Glu Leu Leu Asp Met Ala Val Leu Lys
675 680 685
Asp Tyr Ile Ala Tyr Ala His Ser Thr Ile Met Pro Arg Leu Ser Glu
690 695 700
Glu Ala Ser Gln Ala Leu Ile Glu Ala Tyr Val Asp Met Arg Lys Ile
705 710 715 720
Gly Ser Ser Arg Gly Met Val Ser Ala Tyr Pro Arg Gln Leu Glu Ser
725 730 735
Leu Ile Arg Leu Ala Glu Ala His Ala Lys Val Arg Leu Ser Asn Lys
740 745 750
Val Glu Ala Ile Asp Val Glu Glu Ala Lys Arg Leu His Arg Glu Ala
755 760 765
Leu Lys Gln Ser Ala Thr Asp Pro Arg Thr Gly Ile Val Asp Ile Ser
770 775 780
Ile Leu Thr Thr Gly Met Ser Ala Thr Ser Arg Lys Arg Lys Glu Glu
785 790 795 800
Leu Ala Glu Ala Leu Lys Lys Leu Ile Leu Ser Lys Gly Lys Thr Pro
805 810 815
Ala Leu Lys Tyr Gln Gln Leu Phe Glu Asp Ile Arg Gly Gln Ser Asp
820 825 830
Ile Ala Ile Thr Lys Asp Met Phe Glu Glu Ala Leu Arg Ala Leu Ala
835 840 845
Asp Asp Asp Phe Leu Thr Val Thr Gly Lys Thr Val Arg Leu Leu
850 855 860
<210> 108
<211> 115
<212> PRT
<213> 智人
<400> 108
Met Pro Met Phe Ile Val Asn Thr Asn Val Pro Arg Ala Ser Val Pro
1 5 10 15
Asp Gly Phe Leu Ser Glu Leu Thr Gln Gln Leu Ala Gln Ala Thr Gly
20 25 30
Lys Pro Pro Gln Tyr Ile Ala Val His Val Val Pro Asp Gln Leu Met
35 40 45
Ala Phe Gly Gly Ser Ser Glu Pro Cys Ala Leu Cys Ser Leu His Ser
50 55 60
Ile Gly Lys Ile Gly Gly Ala Gln Asn Arg Ser Tyr Ser Lys Leu Leu
65 70 75 80
Cys Gly Leu Leu Ala Glu Arg Leu Arg Ile Ser Pro Asp Arg Val Tyr
85 90 95
Ile Asn Tyr Tyr Asp Met Asn Ala Ala Asn Val Gly Trp Asn Asn Ser
100 105 110
Thr Phe Ala
115
<210> 109
<211> 267
<212> PRT
<213> 智人
<400> 109
Met Arg Leu Thr Val Leu Cys Ala Val Cys Leu Leu Pro Gly Ser Leu
1 5 10 15
Ala Leu Pro Leu Pro Gln Glu Ala Gly Gly Met Ser Glu Leu Gln Trp
20 25 30
Glu Gln Ala Gln Asp Tyr Leu Lys Arg Phe Tyr Leu Tyr Asp Ser Glu
35 40 45
Thr Lys Asn Ala Asn Ser Leu Glu Ala Lys Leu Lys Glu Met Gln Lys
50 55 60
Phe Phe Gly Leu Pro Ile Thr Gly Met Leu Asn Ser Arg Val Ile Glu
65 70 75 80
Ile Met Gln Lys Pro Arg Cys Gly Val Pro Asp Val Ala Glu Tyr Ser
85 90 95
Leu Phe Pro Asn Ser Pro Lys Trp Thr Ser Lys Val Val Thr Tyr Arg
100 105 110
Ile Val Ser Tyr Thr Arg Asp Leu Pro His Ile Thr Val Asp Arg Leu
115 120 125
Val Ser Lys Ala Leu Asn Met Trp Gly Lys Glu Ile Pro Leu His Phe
130 135 140
Arg Lys Val Val Trp Gly Thr Ala Asp Ile Met Ile Gly Phe Ala Arg
145 150 155 160
Gly Ala His Gly Asp Ser Tyr Pro Phe Asp Gly Pro Gly Asn Thr Leu
165 170 175
Ala His Ala Phe Ala Pro Gly Thr Gly Leu Gly Gly Asp Ala His Phe
180 185 190
Asp Glu Asp Glu Arg Trp Thr Asp Gly Ser Ser Leu Gly Ile Asn Phe
195 200 205
Leu Tyr Ala Ala Thr His Glu Leu Gly His Ser Leu Gly Met Gly His
210 215 220
Ser Ser Asp Pro Asn Ala Val Met Tyr Pro Thr Tyr Gly Asn Gly Asp
225 230 235 240
Pro Gln Asn Phe Lys Leu Ser Gln Asp Asp Ile Lys Gly Ile Gln Lys
245 250 255
Leu Tyr Gly Lys Arg Ser Asn Ser Arg Lys Lys
260 265
<210> 110
<211> 707
<212> PRT
<213> 智人
<400> 110
Met Ser Leu Trp Gln Pro Leu Val Leu Val Leu Leu Val Leu Gly Cys
1 5 10 15
Cys Phe Ala Ala Pro Arg Gln Arg Gln Ser Thr Leu Val Leu Phe Pro
20 25 30
Gly Asp Leu Arg Thr Asn Leu Thr Asp Arg Gln Leu Ala Glu Glu Tyr
35 40 45
Leu Tyr Arg Tyr Gly Tyr Thr Arg Val Ala Glu Met Arg Gly Glu Ser
50 55 60
Lys Ser Leu Gly Pro Ala Leu Leu Leu Leu Gln Lys Gln Leu Ser Leu
65 70 75 80
Pro Glu Thr Gly Glu Leu Asp Ser Ala Thr Leu Lys Ala Met Arg Thr
85 90 95
Pro Arg Cys Gly Val Pro Asp Leu Gly Arg Phe Gln Thr Phe Glu Gly
100 105 110
Asp Leu Lys Trp His His His Asn Ile Thr Tyr Trp Ile Gln Asn Tyr
115 120 125
Ser Glu Asp Leu Pro Arg Ala Val Ile Asp Asp Ala Phe Ala Arg Ala
130 135 140
Phe Ala Leu Trp Ser Ala Val Thr Pro Leu Thr Phe Thr Arg Val Tyr
145 150 155 160
Ser Arg Asp Ala Asp Ile Val Ile Gln Phe Gly Val Ala Glu His Gly
165 170 175
Asp Gly Tyr Pro Phe Asp Gly Lys Asp Gly Leu Leu Ala His Ala Phe
180 185 190
Pro Pro Gly Pro Gly Ile Gln Gly Asp Ala His Phe Asp Asp Asp Glu
195 200 205
Leu Trp Ser Leu Gly Lys Gly Val Val Val Pro Thr Arg Phe Gly Asn
210 215 220
Ala Asp Gly Ala Ala Cys His Phe Pro Phe Ile Phe Glu Gly Arg Ser
225 230 235 240
Tyr Ser Ala Cys Thr Thr Asp Gly Arg Ser Asp Gly Leu Pro Trp Cys
245 250 255
Ser Thr Thr Ala Asn Tyr Asp Thr Asp Asp Arg Phe Gly Phe Cys Pro
260 265 270
Ser Glu Arg Leu Tyr Thr Gln Asp Gly Asn Ala Asp Gly Lys Pro Cys
275 280 285
Gln Phe Pro Phe Ile Phe Gln Gly Gln Ser Tyr Ser Ala Cys Thr Thr
290 295 300
Asp Gly Arg Ser Asp Gly Tyr Arg Trp Cys Ala Thr Thr Ala Asn Tyr
305 310 315 320
Asp Arg Asp Lys Leu Phe Gly Phe Cys Pro Thr Arg Ala Asp Ser Thr
325 330 335
Val Met Gly Gly Asn Ser Ala Gly Glu Leu Cys Val Phe Pro Phe Thr
340 345 350
Phe Leu Gly Lys Glu Tyr Ser Thr Cys Thr Ser Glu Gly Arg Gly Asp
355 360 365
Gly Arg Leu Trp Cys Ala Thr Thr Ser Asn Phe Asp Ser Asp Lys Lys
370 375 380
Trp Gly Phe Cys Pro Asp Gln Gly Tyr Ser Leu Phe Leu Val Ala Ala
385 390 395 400
His Glu Phe Gly His Ala Leu Gly Leu Asp His Ser Ser Val Pro Glu
405 410 415
Ala Leu Met Tyr Pro Met Tyr Arg Phe Thr Glu Gly Pro Pro Leu His
420 425 430
Lys Asp Asp Val Asn Gly Ile Arg His Leu Tyr Gly Pro Arg Pro Glu
435 440 445
Pro Glu Pro Arg Pro Pro Thr Thr Thr Thr Pro Gln Pro Thr Ala Pro
450 455 460
Pro Thr Val Cys Pro Thr Gly Pro Pro Thr Val His Pro Ser Glu Arg
465 470 475 480
Pro Thr Ala Gly Pro Thr Gly Pro Pro Ser Ala Gly Pro Thr Gly Pro
485 490 495
Pro Thr Ala Gly Pro Ser Thr Ala Thr Thr Val Pro Leu Ser Pro Val
500 505 510
Asp Asp Ala Cys Asn Val Asn Ile Phe Asp Ala Ile Ala Glu Ile Gly
515 520 525
Asn Gln Leu Tyr Leu Phe Lys Asp Gly Lys Tyr Trp Arg Phe Ser Glu
530 535 540
Gly Arg Gly Ser Arg Pro Gln Gly Pro Phe Leu Ile Ala Asp Lys Trp
545 550 555 560
Pro Ala Leu Pro Arg Lys Leu Asp Ser Val Phe Glu Glu Arg Leu Ser
565 570 575
Lys Lys Leu Phe Phe Phe Ser Gly Arg Gln Val Trp Val Tyr Thr Gly
580 585 590
Ala Ser Val Leu Gly Pro Arg Arg Leu Asp Lys Leu Gly Leu Gly Ala
595 600 605
Asp Val Ala Gln Val Thr Gly Ala Leu Arg Ser Gly Arg Gly Lys Met
610 615 620
Leu Leu Phe Ser Gly Arg Arg Leu Trp Arg Phe Asp Val Lys Ala Gln
625 630 635 640
Met Val Asp Pro Arg Ser Ala Ser Glu Val Asp Arg Met Phe Pro Gly
645 650 655
Val Pro Leu Asp Thr His Asp Val Phe Gln Tyr Arg Glu Lys Ala Tyr
660 665 670
Phe Cys Gln Asp Arg Phe Tyr Trp Arg Val Ser Ser Arg Ser Glu Leu
675 680 685
Asn Gln Val Asp Gln Val Gly Tyr Val Thr Tyr Asp Ile Leu Gln Cys
690 695 700
Pro Glu Asp
705
<210> 111
<211> 297
<212> PRT
<213> 智人
<400> 111
Met Thr Thr Pro Arg Asn Ser Val Asn Gly Thr Phe Pro Ala Glu Pro
1 5 10 15
Met Lys Gly Pro Ile Ala Met Gln Ser Gly Pro Lys Pro Leu Phe Arg
20 25 30
Arg Met Ser Ser Leu Val Gly Pro Thr Gln Ser Phe Phe Met Arg Glu
35 40 45
Ser Lys Thr Leu Gly Ala Val Gln Ile Met Asn Gly Leu Phe His Ile
50 55 60
Ala Leu Gly Gly Leu Leu Met Ile Pro Ala Gly Ile Tyr Ala Pro Ile
65 70 75 80
Cys Val Thr Val Trp Tyr Pro Leu Trp Gly Gly Ile Met Tyr Ile Ile
85 90 95
Ser Gly Ser Leu Leu Ala Ala Thr Glu Lys Asn Ser Arg Lys Cys Leu
100 105 110
Val Lys Gly Lys Met Ile Met Asn Ser Leu Ser Leu Phe Ala Ala Ile
115 120 125
Ser Gly Met Ile Leu Ser Ile Met Asp Ile Leu Asn Ile Lys Ile Ser
130 135 140
His Phe Leu Lys Met Glu Ser Leu Asn Phe Ile Arg Ala His Thr Pro
145 150 155 160
Tyr Ile Asn Ile Tyr Asn Cys Glu Pro Ala Asn Pro Ser Glu Lys Asn
165 170 175
Ser Pro Ser Thr Gln Tyr Cys Tyr Ser Ile Gln Ser Leu Phe Leu Gly
180 185 190
Ile Leu Ser Val Met Leu Ile Phe Ala Phe Phe Gln Glu Leu Val Ile
195 200 205
Ala Gly Ile Val Glu Asn Glu Trp Lys Arg Thr Cys Ser Arg Pro Lys
210 215 220
Ser Asn Ile Val Leu Leu Ser Ala Glu Glu Lys Lys Glu Gln Thr Ile
225 230 235 240
Glu Ile Lys Glu Glu Val Val Gly Leu Thr Glu Thr Ser Ser Gln Pro
245 250 255
Lys Asn Glu Glu Asp Ile Glu Ile Ile Pro Ile Gln Glu Glu Glu Glu
260 265 270
Glu Glu Thr Glu Thr Asn Phe Pro Glu Pro Pro Gln Asp Gln Glu Ser
275 280 285
Ser Pro Ile Glu Asn Asp Ser Ser Pro
290 295
<210> 112
<211> 151
<212> PRT
<213> 智人
<400> 112
Met Cys Asp Phe Thr Glu Asp Gln Thr Ala Glu Phe Lys Glu Ala Phe
1 5 10 15
Gln Leu Phe Asp Arg Thr Gly Asp Gly Lys Ile Leu Tyr Ser Gln Cys
20 25 30
Gly Asp Val Met Arg Ala Leu Gly Gln Asn Pro Thr Asn Ala Glu Val
35 40 45
Leu Lys Val Leu Gly Asn Pro Lys Ser Asp Glu Met Asn Val Lys Val
50 55 60
Leu Asp Phe Glu His Phe Leu Pro Met Leu Gln Thr Val Ala Lys Asn
65 70 75 80
Lys Asp Gln Gly Thr Tyr Glu Asp Tyr Val Glu Gly Leu Arg Val Phe
85 90 95
Asp Lys Glu Gly Asn Gly Thr Val Met Gly Ala Glu Ile Arg His Val
100 105 110
Leu Val Thr Leu Gly Glu Lys Met Thr Glu Glu Glu Val Glu Met Leu
115 120 125
Val Ala Gly His Glu Asp Ser Asn Gly Cys Ile Asn Tyr Glu Ala Phe
130 135 140
Val Arg His Ile Leu Ser Gly
145 150
<210> 113
<211> 172
<212> PRT
<213> 智人
<400> 113
Met Ser Ser Lys Arg Ala Lys Ala Lys Thr Thr Lys Lys Arg Pro Gln
1 5 10 15
Arg Ala Thr Ser Asn Val Phe Ala Met Phe Asp Gln Ser Gln Ile Gln
20 25 30
Glu Phe Lys Glu Ala Phe Asn Met Ile Asp Gln Asn Arg Asp Gly Phe
35 40 45
Ile Asp Lys Glu Asp Leu His Asp Met Leu Ala Ser Leu Gly Lys Asn
50 55 60
Pro Thr Asp Glu Tyr Leu Glu Gly Met Met Ser Glu Ala Pro Gly Pro
65 70 75 80
Ile Asn Phe Thr Met Phe Leu Thr Met Phe Gly Glu Lys Leu Asn Gly
85 90 95
Thr Asp Pro Glu Asp Val Ile Arg Asn Ala Phe Ala Cys Phe Asp Glu
100 105 110
Glu Ala Ser Gly Phe Ile His Glu Asp His Leu Arg Glu Leu Leu Thr
115 120 125
Thr Met Gly Asp Arg Phe Thr Asp Glu Glu Val Asp Glu Met Tyr Arg
130 135 140
Glu Ala Pro Ile Asp Lys Lys Gly Asn Phe Asn Tyr Val Glu Phe Thr
145 150 155 160
Arg Ile Leu Lys His Gly Ala Lys Asp Lys Asp Asp
165 170
<210> 114
<211> 152
<212> PRT
<213> 智人
<400> 114
Met Ala Asn Cys Glu Arg Thr Phe Ile Ala Ile Lys Pro Asp Gly Val
1 5 10 15
Gln Arg Gly Leu Val Gly Glu Ile Ile Lys Arg Phe Glu Gln Lys Gly
20 25 30
Phe Arg Leu Val Gly Leu Lys Phe Met Gln Ala Ser Glu Asp Leu Leu
35 40 45
Lys Glu His Tyr Val Asp Leu Lys Asp Arg Pro Phe Phe Ala Gly Leu
50 55 60
Val Lys Tyr Met His Ser Gly Pro Val Val Ala Met Val Trp Glu Gly
65 70 75 80
Leu Asn Val Val Lys Thr Gly Arg Val Met Leu Gly Glu Thr Asn Pro
85 90 95
Ala Asp Ser Lys Pro Gly Thr Ile Arg Gly Asp Phe Cys Ile Gln Val
100 105 110
Gly Arg Asn Ile Ile His Gly Ser Asp Ser Val Glu Ser Ala Glu Lys
115 120 125
Glu Ile Gly Leu Trp Phe His Pro Glu Glu Leu Val Asp Tyr Thr Ser
130 135 140
Cys Ala Gln Asn Trp Ile Tyr Glu
145 150
<210> 115
<211> 264
<212> PRT
<213> 智人
<400> 115
Met Glu Ser Gly Phe Thr Ser Lys Asp Thr Tyr Leu Ser His Phe Asn
1 5 10 15
Pro Arg Asp Tyr Leu Glu Lys Tyr Tyr Lys Phe Gly Ser Arg His Ser
20 25 30
Ala Glu Ser Gln Ile Leu Lys His Leu Leu Lys Asn Leu Phe Lys Ile
35 40 45
Phe Cys Leu Asp Gly Val Lys Gly Asp Leu Leu Ile Asp Ile Gly Ser
50 55 60
Gly Pro Thr Ile Tyr Gln Leu Leu Ser Ala Cys Glu Ser Phe Lys Glu
65 70 75 80
Ile Val Val Thr Asp Tyr Ser Asp Gln Asn Leu Gln Glu Leu Glu Lys
85 90 95
Trp Leu Lys Lys Glu Pro Glu Ala Phe Asp Trp Ser Pro Val Val Thr
100 105 110
Tyr Val Cys Asp Leu Glu Gly Asn Arg Val Lys Gly Pro Glu Lys Glu
115 120 125
Glu Lys Leu Arg Gln Ala Val Lys Gln Val Leu Lys Cys Asp Val Thr
130 135 140
Gln Ser Gln Pro Leu Gly Ala Val Pro Leu Pro Pro Ala Asp Cys Val
145 150 155 160
Leu Ser Thr Leu Cys Leu Asp Ala Ala Cys Pro Asp Leu Pro Thr Tyr
165 170 175
Cys Arg Ala Leu Arg Asn Leu Gly Ser Leu Leu Lys Pro Gly Gly Phe
180 185 190
Leu Val Ile Met Asp Ala Leu Lys Ser Ser Tyr Tyr Met Ile Gly Glu
195 200 205
Gln Lys Phe Ser Ser Leu Pro Leu Gly Arg Glu Ala Val Glu Ala Ala
210 215 220
Val Lys Glu Ala Gly Tyr Thr Ile Glu Trp Phe Glu Val Ile Ser Gln
225 230 235 240
Ser Tyr Ser Ser Thr Met Ala Asn Asn Glu Gly Leu Phe Ser Leu Val
245 250 255
Ala Arg Lys Leu Ser Arg Pro Leu
260
<210> 116
<211> 201
<212> PRT
<213> 智人
<400> 116
Met Ala Leu Ser Trp Val Leu Thr Val Leu Ser Leu Leu Pro Leu Leu
1 5 10 15
Glu Ala Gln Ile Pro Leu Cys Ala Asn Leu Val Pro Val Pro Ile Thr
20 25 30
Asn Ala Thr Leu Asp Gln Ile Thr Gly Lys Trp Phe Tyr Ile Ala Ser
35 40 45
Ala Phe Arg Asn Glu Glu Tyr Asn Lys Ser Val Gln Glu Ile Gln Ala
50 55 60
Thr Phe Phe Tyr Phe Thr Pro Asn Lys Thr Glu Asp Thr Ile Phe Leu
65 70 75 80
Arg Glu Tyr Gln Thr Arg Gln Asp Gln Cys Ile Tyr Asn Thr Thr Tyr
85 90 95
Leu Asn Val Gln Arg Glu Asn Gly Thr Ile Ser Arg Tyr Val Gly Gly
100 105 110
Gln Glu His Phe Ala His Leu Leu Ile Leu Arg Asp Thr Lys Thr Tyr
115 120 125
Met Leu Ala Phe Asp Val Asn Asp Glu Lys Asn Trp Gly Leu Ser Val
130 135 140
Tyr Ala Asp Lys Pro Glu Thr Thr Lys Glu Gln Leu Gly Glu Phe Tyr
145 150 155 160
Glu Ala Leu Asp Cys Leu Arg Ile Pro Lys Ser Asp Val Val Tyr Thr
165 170 175
Asp Trp Lys Lys Asp Lys Cys Glu Pro Leu Glu Lys Gln His Glu Lys
180 185 190
Glu Arg Lys Gln Glu Glu Gly Glu Ser
195 200
<210> 117
<211> 640
<212> PRT
<213> 智人
<400> 117
Met Ala Ala Leu Tyr Arg Pro Gly Leu Arg Leu Asn Trp His Gly Leu
1 5 10 15
Ser Pro Leu Gly Trp Pro Ser Cys Arg Ser Ile Gln Thr Leu Arg Val
20 25 30
Leu Ser Gly Asp Leu Gly Gln Leu Pro Thr Gly Ile Arg Asp Phe Val
35 40 45
Glu His Ser Ala Arg Leu Cys Gln Pro Glu Gly Ile His Ile Cys Asp
50 55 60
Gly Thr Glu Ala Glu Asn Thr Ala Thr Leu Thr Leu Leu Glu Gln Gln
65 70 75 80
Gly Leu Ile Arg Lys Leu Pro Lys Tyr Asn Asn Cys Trp Leu Ala Arg
85 90 95
Thr Asp Pro Lys Asp Val Ala Arg Val Glu Ser Lys Thr Val Ile Val
100 105 110
Thr Pro Ser Gln Arg Asp Thr Val Gln Leu Pro Pro Gly Gly Ala Arg
115 120 125
Gly Gln Leu Gly Asn Trp Met Ser Pro Ala Asp Phe Gln Arg Ala Val
130 135 140
Asp Glu Arg Phe Pro Gly Cys Met Gln Gly Arg Thr Met Tyr Val Leu
145 150 155 160
Pro Phe Ser Met Gly Pro Val Gly Ser Pro Leu Ser Arg Ile Gly Val
165 170 175
Gln Leu Thr Asp Ser Ala Tyr Val Val Ala Ser Met Arg Ile Met Thr
180 185 190
Arg Leu Gly Thr Pro Val Leu Gln Ala Leu Gly Asp Gly Asp Phe Val
195 200 205
Lys Cys Leu His Ser Val Gly Gln Pro Leu Thr Gly Gln Gly Glu Pro
210 215 220
Val Ser Gln Trp Pro Cys Asn Pro Glu Lys Thr Leu Ile Gly His Val
225 230 235 240
Pro Asp Gln Arg Glu Ile Ile Ser Phe Gly Ser Gly Tyr Gly Gly Asn
245 250 255
Ser Leu Leu Gly Lys Lys Cys Phe Ala Leu Arg Ile Ala Ser Arg Leu
260 265 270
Ala Arg Asp Glu Gly Trp Leu Ala Glu His Met Leu Ile Leu Gly Ile
275 280 285
Thr Ser Pro Ala Gly Lys Lys Arg Tyr Val Ala Ala Ala Phe Pro Ser
290 295 300
Ala Cys Gly Lys Thr Asn Leu Ala Met Met Arg Pro Ala Leu Pro Gly
305 310 315 320
Trp Lys Val Glu Cys Val Gly Asp Asp Ile Ala Trp Met Arg Phe Asp
325 330 335
Ser Glu Gly Arg Leu Arg Ala Ile Asn Pro Glu Asn Gly Phe Phe Gly
340 345 350
Val Ala Pro Gly Thr Ser Ala Thr Thr Asn Pro Asn Ala Met Ala Thr
355 360 365
Ile Gln Ser Asn Thr Ile Phe Thr Asn Val Ala Glu Thr Ser Asp Gly
370 375 380
Gly Val Tyr Trp Glu Gly Ile Asp Gln Pro Leu Pro Pro Gly Val Thr
385 390 395 400
Val Thr Ser Trp Leu Gly Lys Pro Trp Lys Pro Gly Asp Lys Glu Pro
405 410 415
Cys Ala His Pro Asn Ser Arg Phe Cys Ala Pro Ala Arg Gln Cys Pro
420 425 430
Ile Met Asp Pro Ala Trp Glu Ala Pro Glu Gly Val Pro Ile Asp Ala
435 440 445
Ile Ile Phe Gly Gly Arg Arg Pro Lys Gly Val Pro Leu Val Tyr Glu
450 455 460
Ala Phe Asn Trp Arg His Gly Val Phe Val Gly Ser Ala Met Arg Ser
465 470 475 480
Glu Ser Thr Ala Ala Ala Glu His Lys Gly Lys Ile Ile Met His Asp
485 490 495
Pro Phe Ala Met Arg Pro Phe Phe Gly Tyr Asn Phe Gly His Tyr Leu
500 505 510
Glu His Trp Leu Ser Met Glu Gly Arg Lys Gly Ala Gln Leu Pro Arg
515 520 525
Ile Phe His Val Asn Trp Phe Arg Arg Asp Glu Ala Gly His Phe Leu
530 535 540
Trp Pro Gly Phe Gly Glu Asn Ala Arg Val Leu Asp Trp Ile Cys Arg
545 550 555 560
Arg Leu Glu Gly Glu Asp Ser Ala Arg Glu Thr Pro Ile Gly Leu Val
565 570 575
Pro Lys Glu Gly Ala Leu Asp Leu Ser Gly Leu Arg Ala Ile Asp Thr
580 585 590
Thr Gln Leu Phe Ser Leu Pro Lys Asp Phe Trp Glu Gln Glu Val Arg
595 600 605
Asp Ile Arg Ser Tyr Leu Thr Glu Gln Val Asn Gln Asp Leu Pro Lys
610 615 620
Glu Val Leu Ala Glu Leu Glu Ala Leu Glu Arg Arg Val His Lys Met
625 630 635 640
<210> 118
<211> 505
<212> PRT
<213> 智人
<400> 118
Met Arg Leu Arg Arg Leu Ala Leu Phe Pro Gly Val Ala Leu Leu Leu
1 5 10 15
Ala Ala Ala Arg Leu Ala Ala Ala Ser Asp Val Leu Glu Leu Thr Asp
20 25 30
Asp Asn Phe Glu Ser Arg Ile Ser Asp Thr Gly Ser Ala Gly Leu Met
35 40 45
Leu Val Glu Phe Phe Ala Pro Trp Cys Gly His Cys Lys Arg Leu Ala
50 55 60
Pro Glu Tyr Glu Ala Ala Ala Thr Arg Leu Lys Gly Ile Val Pro Leu
65 70 75 80
Ala Lys Val Asp Cys Thr Ala Asn Thr Asn Thr Cys Asn Lys Tyr Gly
85 90 95
Val Ser Gly Tyr Pro Thr Leu Lys Ile Phe Arg Asp Gly Glu Glu Ala
100 105 110
Gly Ala Tyr Asp Gly Pro Arg Thr Ala Asp Gly Ile Val Ser His Leu
115 120 125
Lys Lys Gln Ala Gly Pro Ala Ser Val Pro Leu Arg Thr Glu Glu Glu
130 135 140
Phe Lys Lys Phe Ile Ser Asp Lys Asp Ala Ser Ile Val Gly Phe Phe
145 150 155 160
Asp Asp Ser Phe Ser Glu Ala His Ser Glu Phe Leu Lys Ala Ala Ser
165 170 175
Asn Leu Arg Asp Asn Tyr Arg Phe Ala His Thr Asn Val Glu Ser Leu
180 185 190
Val Asn Glu Tyr Asp Asp Asn Gly Glu Gly Ile Ile Leu Phe Arg Pro
195 200 205
Ser His Leu Thr Asn Lys Phe Glu Asp Lys Thr Val Ala Tyr Thr Glu
210 215 220
Gln Lys Met Thr Ser Gly Lys Ile Lys Lys Phe Ile Gln Glu Asn Ile
225 230 235 240
Phe Gly Ile Cys Pro His Met Thr Glu Asp Asn Lys Asp Leu Ile Gln
245 250 255
Gly Lys Asp Leu Leu Ile Ala Tyr Tyr Asp Val Asp Tyr Glu Lys Asn
260 265 270
Ala Lys Gly Ser Asn Tyr Trp Arg Asn Arg Val Met Met Val Ala Lys
275 280 285
Lys Phe Leu Asp Ala Gly His Lys Leu Asn Phe Ala Val Ala Ser Arg
290 295 300
Lys Thr Phe Ser His Glu Leu Ser Asp Phe Gly Leu Glu Ser Thr Ala
305 310 315 320
Gly Glu Ile Pro Val Val Ala Ile Arg Thr Ala Lys Gly Glu Lys Phe
325 330 335
Val Met Gln Glu Glu Phe Ser Arg Asp Gly Lys Ala Leu Glu Arg Phe
340 345 350
Leu Gln Asp Tyr Phe Asp Gly Asn Leu Lys Arg Tyr Leu Lys Ser Glu
355 360 365
Pro Ile Pro Glu Ser Asn Asp Gly Pro Val Lys Val Val Val Ala Glu
370 375 380
Asn Phe Asp Glu Ile Val Asn Asn Glu Asn Lys Asp Val Leu Ile Glu
385 390 395 400
Phe Tyr Ala Pro Trp Cys Gly His Cys Lys Asn Leu Glu Pro Lys Tyr
405 410 415
Lys Glu Leu Gly Glu Lys Leu Ser Lys Asp Pro Asn Ile Val Ile Ala
420 425 430
Lys Met Asp Ala Thr Ala Asn Asp Val Pro Ser Pro Tyr Glu Val Arg
435 440 445
Gly Phe Pro Thr Ile Tyr Phe Ser Pro Ala Asn Lys Lys Leu Asn Pro
450 455 460
Lys Lys Tyr Glu Gly Gly Arg Glu Leu Ser Asp Phe Ile Ser Tyr Leu
465 470 475 480
Gln Arg Glu Ala Thr Asn Pro Pro Val Ile Gln Glu Glu Lys Pro Lys
485 490 495
Lys Lys Lys Lys Ala Gln Glu Asp Leu
500 505
<210> 119
<211> 440
<212> PRT
<213> 智人
<400> 119
Met Ala Leu Leu Val Leu Gly Leu Val Ser Cys Thr Phe Phe Leu Ala
1 5 10 15
Val Asn Gly Leu Tyr Ser Ser Ser Asp Asp Val Ile Glu Leu Thr Pro
20 25 30
Ser Asn Phe Asn Arg Glu Val Ile Gln Ser Asp Ser Leu Trp Leu Val
35 40 45
Glu Phe Tyr Ala Pro Trp Cys Gly His Cys Gln Arg Leu Thr Pro Glu
50 55 60
Trp Lys Lys Ala Ala Thr Ala Leu Lys Asp Val Val Lys Val Gly Ala
65 70 75 80
Val Asp Ala Asp Lys His His Ser Leu Gly Gly Gln Tyr Gly Val Gln
85 90 95
Gly Phe Pro Thr Ile Lys Ile Phe Gly Ser Asn Lys Asn Arg Pro Glu
100 105 110
Asp Tyr Gln Gly Gly Arg Thr Gly Glu Ala Ile Val Asp Ala Ala Leu
115 120 125
Ser Ala Leu Arg Gln Leu Val Lys Asp Arg Leu Gly Gly Arg Ser Gly
130 135 140
Gly Tyr Ser Ser Gly Lys Gln Gly Arg Ser Asp Ser Ser Ser Lys Lys
145 150 155 160
Asp Val Ile Glu Leu Thr Asp Asp Ser Phe Asp Lys Asn Val Leu Asp
165 170 175
Ser Glu Asp Val Trp Met Val Glu Phe Tyr Ala Pro Trp Cys Gly His
180 185 190
Cys Lys Asn Leu Glu Pro Glu Trp Ala Ala Ala Ala Ser Glu Val Lys
195 200 205
Glu Gln Thr Lys Gly Lys Val Lys Leu Ala Ala Val Asp Ala Thr Val
210 215 220
Asn Gln Val Leu Ala Ser Arg Tyr Gly Ile Arg Gly Phe Pro Thr Ile
225 230 235 240
Lys Ile Phe Gln Lys Gly Glu Ser Pro Val Asp Tyr Asp Gly Gly Arg
245 250 255
Thr Arg Ser Asp Ile Val Ser Arg Ala Leu Asp Leu Phe Ser Asp Asn
260 265 270
Ala Pro Pro Pro Glu Leu Leu Glu Ile Ile Asn Glu Asp Ile Ala Lys
275 280 285
Arg Thr Cys Glu Glu His Gln Leu Cys Val Val Ala Val Leu Pro His
290 295 300
Ile Leu Asp Thr Gly Ala Ala Gly Arg Asn Ser Tyr Leu Glu Val Leu
305 310 315 320
Leu Lys Leu Ala Asp Lys Tyr Lys Lys Lys Met Trp Gly Trp Leu Trp
325 330 335
Thr Glu Ala Gly Ala Gln Ser Glu Leu Glu Thr Ala Leu Gly Ile Gly
340 345 350
Gly Phe Gly Tyr Pro Ala Met Ala Ala Ile Asn Ala Arg Lys Met Lys
355 360 365
Phe Ala Leu Leu Lys Gly Ser Phe Ser Glu Gln Gly Ile Asn Glu Phe
370 375 380
Leu Arg Glu Leu Ser Phe Gly Arg Gly Ser Thr Ala Pro Val Gly Gly
385 390 395 400
Gly Ala Phe Pro Thr Ile Val Glu Arg Glu Pro Trp Asp Gly Arg Asp
405 410 415
Gly Glu Leu Pro Val Glu Asp Asp Ile Asp Leu Ser Asp Val Glu Leu
420 425 430
Asp Asp Leu Gly Lys Asp Glu Leu
435 440
<210> 120
<211> 312
<212> PRT
<213> 智人
<400> 120
Met Glu Glu Glu Cys Arg Val Leu Ser Ile Gln Ser His Val Ile Arg
1 5 10 15
Gly Tyr Val Gly Asn Arg Ala Ala Thr Phe Pro Leu Gln Val Leu Gly
20 25 30
Phe Glu Ile Asp Ala Val Asn Ser Val Gln Phe Ser Asn His Thr Gly
35 40 45
Tyr Ala His Trp Lys Gly Gln Val Leu Asn Ser Asp Glu Leu Gln Glu
50 55 60
Leu Tyr Glu Gly Leu Arg Leu Asn Asn Met Asn Lys Tyr Asp Tyr Val
65 70 75 80
Leu Thr Gly Tyr Thr Arg Asp Lys Ser Phe Leu Ala Met Val Val Asp
85 90 95
Ile Val Gln Glu Leu Lys Gln Gln Asn Pro Arg Leu Val Tyr Val Cys
100 105 110
Asp Pro Val Leu Gly Asp Lys Trp Asp Gly Glu Gly Ser Met Tyr Val
115 120 125
Pro Glu Asp Leu Leu Pro Val Tyr Lys Glu Lys Val Val Pro Leu Ala
130 135 140
Asp Ile Ile Thr Pro Asn Gln Phe Glu Ala Glu Leu Leu Ser Gly Arg
145 150 155 160
Lys Ile His Ser Gln Glu Glu Ala Leu Arg Val Met Asp Met Leu His
165 170 175
Ser Met Gly Pro Asp Thr Val Val Ile Thr Ser Ser Asp Leu Pro Ser
180 185 190
Pro Gln Gly Ser Asn Tyr Leu Ile Val Leu Gly Ser Gln Arg Arg Arg
195 200 205
Asn Pro Ala Gly Ser Val Val Met Glu Arg Ile Arg Met Asp Ile Arg
210 215 220
Lys Val Asp Ala Val Phe Val Gly Thr Gly Asp Leu Phe Ala Ala Met
225 230 235 240
Leu Leu Ala Trp Thr His Lys His Pro Asn Asn Leu Lys Val Ala Cys
245 250 255
Glu Lys Thr Val Ser Thr Leu His His Val Leu Gln Arg Thr Ile Gln
260 265 270
Cys Ala Lys Ala Gln Ala Gly Glu Gly Val Arg Pro Ser Pro Met Gln
275 280 285
Leu Glu Leu Arg Met Val Gln Ser Lys Arg Asp Ile Glu Asp Pro Glu
290 295 300
Ile Val Val Gln Ala Thr Val Leu
305 310
<210> 121
<211> 187
<212> PRT
<213> 智人
<400> 121
Met Pro Val Asp Leu Ser Lys Trp Ser Gly Pro Leu Ser Leu Gln Glu
1 5 10 15
Val Asp Glu Gln Pro Gln His Pro Leu His Val Thr Tyr Ala Gly Ala
20 25 30
Ala Val Asp Glu Leu Gly Lys Val Leu Thr Pro Thr Gln Val Lys Asn
35 40 45
Arg Pro Thr Ser Ile Ser Trp Asp Gly Leu Asp Ser Gly Lys Leu Tyr
50 55 60
Thr Leu Val Leu Thr Asp Pro Asp Ala Pro Ser Arg Lys Asp Pro Lys
65 70 75 80
Tyr Arg Glu Trp His His Phe Leu Val Val Asn Met Lys Gly Asn Asp
85 90 95
Ile Ser Ser Gly Thr Val Leu Ser Asp Tyr Val Gly Ser Gly Pro Pro
100 105 110
Lys Gly Thr Gly Leu His Arg Tyr Val Trp Leu Val Tyr Glu Gln Asp
115 120 125
Arg Pro Leu Lys Cys Asp Glu Pro Ile Leu Ser Asn Arg Ser Gly Asp
130 135 140
His Arg Gly Lys Phe Lys Val Ala Ser Phe Arg Lys Lys Tyr Glu Leu
145 150 155 160
Arg Ala Pro Val Ala Gly Thr Cys Tyr Gln Ala Glu Trp Asp Asp Tyr
165 170 175
Val Pro Lys Leu Tyr Glu Gln Leu Ser Gly Lys
180 185
<210> 122
<211> 270
<212> PRT
<213> 智人
<400> 122
Met Val Leu Leu Lys Glu Tyr Arg Val Ile Leu Pro Val Ser Val Asp
1 5 10 15
Glu Tyr Gln Val Gly Gln Leu Tyr Ser Val Ala Glu Ala Ser Lys Asn
20 25 30
Glu Thr Gly Gly Gly Glu Gly Val Glu Val Leu Val Asn Glu Pro Tyr
35 40 45
Glu Lys Asp Gly Glu Lys Gly Gln Tyr Thr His Lys Ile Tyr His Leu
50 55 60
Gln Ser Lys Val Pro Thr Phe Val Arg Met Leu Ala Pro Glu Gly Ala
65 70 75 80
Leu Asn Ile His Glu Lys Ala Trp Asn Ala Tyr Pro Tyr Cys Arg Thr
85 90 95
Val Ile Thr Asn Glu Tyr Met Lys Glu Asp Phe Leu Ile Lys Ile Glu
100 105 110
Thr Trp His Lys Pro Asp Leu Gly Thr Gln Glu Asn Val His Lys Leu
115 120 125
Glu Pro Glu Ala Trp Lys His Val Glu Ala Val Tyr Ile Asp Ile Ala
130 135 140
Asp Arg Ser Gln Val Leu Ser Lys Asp Tyr Lys Ala Glu Glu Asp Pro
145 150 155 160
Ala Lys Phe Lys Ser Ile Lys Thr Gly Arg Gly Pro Leu Gly Pro Asn
165 170 175
Trp Lys Gln Glu Leu Val Asn Gln Lys Asp Cys Pro Tyr Met Cys Ala
180 185 190
Tyr Lys Leu Val Thr Val Lys Phe Lys Trp Trp Gly Leu Gln Asn Lys
195 200 205
Val Glu Asn Phe Ile His Lys Gln Glu Arg Arg Leu Phe Thr Asn Phe
210 215 220
His Arg Gln Leu Phe Cys Trp Leu Asp Lys Trp Val Asp Leu Thr Met
225 230 235 240
Asp Asp Ile Arg Arg Met Glu Glu Glu Thr Lys Arg Gln Leu Asp Glu
245 250 255
Met Arg Gln Lys Asp Pro Val Lys Gly Met Thr Ala Asp Asp
260 265 270
<210> 123
<211> 531
<212> PRT
<213> 智人
<400> 123
Met Ser Lys Pro His Ser Glu Ala Gly Thr Ala Phe Ile Gln Thr Gln
1 5 10 15
Gln Leu His Ala Ala Met Ala Asp Thr Phe Leu Glu His Met Cys Arg
20 25 30
Leu Asp Ile Asp Ser Pro Pro Ile Thr Ala Arg Asn Thr Gly Ile Ile
35 40 45
Cys Thr Ile Gly Pro Ala Ser Arg Ser Val Glu Thr Leu Lys Glu Met
50 55 60
Ile Lys Ser Gly Met Asn Val Ala Arg Leu Asn Phe Ser His Gly Thr
65 70 75 80
His Glu Tyr His Ala Glu Thr Ile Lys Asn Val Arg Thr Ala Thr Glu
85 90 95
Ser Phe Ala Ser Asp Pro Ile Leu Tyr Arg Pro Val Ala Val Ala Leu
100 105 110
Asp Thr Lys Gly Pro Glu Ile Arg Thr Gly Leu Ile Lys Gly Ser Gly
115 120 125
Thr Ala Glu Val Glu Leu Lys Lys Gly Ala Thr Leu Lys Ile Thr Leu
130 135 140
Asp Asn Ala Tyr Met Glu Lys Cys Asp Glu Asn Ile Leu Trp Leu Asp
145 150 155 160
Tyr Lys Asn Ile Cys Lys Val Val Glu Val Gly Ser Lys Ile Tyr Val
165 170 175
Asp Asp Gly Leu Ile Ser Leu Gln Val Lys Gln Lys Gly Ala Asp Phe
180 185 190
Leu Val Thr Glu Val Glu Asn Gly Gly Ser Leu Gly Ser Lys Lys Gly
195 200 205
Val Asn Leu Pro Gly Ala Ala Val Asp Leu Pro Ala Val Ser Glu Lys
210 215 220
Asp Ile Gln Asp Leu Lys Phe Gly Val Glu Gln Asp Val Asp Met Val
225 230 235 240
Phe Ala Ser Phe Ile Arg Lys Ala Ser Asp Val His Glu Val Arg Lys
245 250 255
Val Leu Gly Glu Lys Gly Lys Asn Ile Lys Ile Ile Ser Lys Ile Glu
260 265 270
Asn His Glu Gly Val Arg Arg Phe Asp Glu Ile Leu Glu Ala Ser Asp
275 280 285
Gly Ile Met Val Ala Arg Gly Asp Leu Gly Ile Glu Ile Pro Ala Glu
290 295 300
Lys Val Phe Leu Ala Gln Lys Met Met Ile Gly Arg Cys Asn Arg Ala
305 310 315 320
Gly Lys Pro Val Ile Cys Ala Thr Gln Met Leu Glu Ser Met Ile Lys
325 330 335
Lys Pro Arg Pro Thr Arg Ala Glu Gly Ser Asp Val Ala Asn Ala Val
340 345 350
Leu Asp Gly Ala Asp Cys Ile Met Leu Ser Gly Glu Thr Ala Lys Gly
355 360 365
Asp Tyr Pro Leu Glu Ala Val Arg Met Gln His Leu Ile Ala Arg Glu
370 375 380
Ala Glu Ala Ala Ile Tyr His Leu Gln Leu Phe Glu Glu Leu Arg Arg
385 390 395 400
Leu Ala Pro Ile Thr Ser Asp Pro Thr Glu Ala Thr Ala Val Gly Ala
405 410 415
Val Glu Ala Ser Phe Lys Cys Cys Ser Gly Ala Ile Ile Val Leu Thr
420 425 430
Lys Ser Gly Arg Ser Ala His Gln Val Ala Arg Tyr Arg Pro Arg Ala
435 440 445
Pro Ile Ile Ala Val Thr Arg Asn Pro Gln Thr Ala Arg Gln Ala His
450 455 460
Leu Tyr Arg Gly Ile Phe Pro Val Leu Cys Lys Asp Pro Val Gln Glu
465 470 475 480
Ala Trp Ala Glu Asp Val Asp Leu Arg Val Asn Phe Ala Met Asn Val
485 490 495
Gly Lys Ala Arg Gly Phe Phe Lys Lys Gly Asp Val Val Ile Val Leu
500 505 510
Thr Gly Trp Arg Pro Gly Ser Gly Phe Thr Asn Thr Met Arg Val Val
515 520 525
Pro Val Pro
530
<210> 124
<211> 431
<212> PRT
<213> 智人
<400> 124
Met Arg Ala Leu Leu Ala Arg Leu Leu Leu Cys Val Leu Val Val Ser
1 5 10 15
Asp Ser Lys Gly Ser Asn Glu Leu His Gln Val Pro Ser Asn Cys Asp
20 25 30
Cys Leu Asn Gly Gly Thr Cys Val Ser Asn Lys Tyr Phe Ser Asn Ile
35 40 45
His Trp Cys Asn Cys Pro Lys Lys Phe Gly Gly Gln His Cys Glu Ile
50 55 60
Asp Lys Ser Lys Thr Cys Tyr Glu Gly Asn Gly His Phe Tyr Arg Gly
65 70 75 80
Lys Ala Ser Thr Asp Thr Met Gly Arg Pro Cys Leu Pro Trp Asn Ser
85 90 95
Ala Thr Val Leu Gln Gln Thr Tyr His Ala His Arg Ser Asp Ala Leu
100 105 110
Gln Leu Gly Leu Gly Lys His Asn Tyr Cys Arg Asn Pro Asp Asn Arg
115 120 125
Arg Arg Pro Trp Cys Tyr Val Gln Val Gly Leu Lys Pro Leu Val Gln
130 135 140
Glu Cys Met Val His Asp Cys Ala Asp Gly Lys Lys Pro Ser Ser Pro
145 150 155 160
Pro Glu Glu Leu Lys Phe Gln Cys Gly Gln Lys Thr Leu Arg Pro Arg
165 170 175
Phe Lys Ile Ile Gly Gly Glu Phe Thr Thr Ile Glu Asn Gln Pro Trp
180 185 190
Phe Ala Ala Ile Tyr Arg Arg His Arg Gly Gly Ser Val Thr Tyr Val
195 200 205
Cys Gly Gly Ser Leu Ile Ser Pro Cys Trp Val Ile Ser Ala Thr His
210 215 220
Cys Phe Ile Asp Tyr Pro Lys Lys Glu Asp Tyr Ile Val Tyr Leu Gly
225 230 235 240
Arg Ser Arg Leu Asn Ser Asn Thr Gln Gly Glu Met Lys Phe Glu Val
245 250 255
Glu Asn Leu Ile Leu His Lys Asp Tyr Ser Ala Asp Thr Leu Ala His
260 265 270
His Asn Asp Ile Ala Leu Leu Lys Ile Arg Ser Lys Glu Gly Arg Cys
275 280 285
Ala Gln Pro Ser Arg Thr Ile Gln Thr Ile Cys Leu Pro Ser Met Tyr
290 295 300
Asn Asp Pro Gln Phe Gly Thr Ser Cys Glu Ile Thr Gly Phe Gly Lys
305 310 315 320
Glu Asn Ser Thr Asp Tyr Leu Tyr Pro Glu Gln Leu Lys Met Thr Val
325 330 335
Val Lys Leu Ile Ser His Arg Glu Cys Gln Gln Pro His Tyr Tyr Gly
340 345 350
Ser Glu Val Thr Thr Lys Met Leu Cys Ala Ala Asp Pro Gln Trp Lys
355 360 365
Thr Asp Ser Cys Gln Gly Asp Ser Gly Gly Pro Leu Val Cys Ser Leu
370 375 380
Gln Gly Arg Met Thr Leu Thr Gly Ile Val Ser Trp Gly Arg Gly Cys
385 390 395 400
Ala Leu Lys Asp Lys Pro Gly Val Tyr Thr Arg Val Ser His Phe Leu
405 410 415
Pro Trp Ile Arg Ser His Thr Lys Glu Glu Asn Gly Leu Ala Leu
420 425 430
<210> 125
<211> 289
<212> PRT
<213> 智人
<400> 125
Met Ser Gly Phe Ser Thr Glu Glu Arg Ala Ala Pro Phe Ser Leu Glu
1 5 10 15
Tyr Arg Val Phe Leu Lys Asn Glu Lys Gly Gln Tyr Ile Ser Pro Phe
20 25 30
His Asp Ile Pro Ile Tyr Ala Asp Lys Asp Val Phe His Met Val Val
35 40 45
Glu Val Pro Arg Trp Ser Asn Ala Lys Met Glu Ile Ala Thr Lys Asp
50 55 60
Pro Leu Asn Pro Ile Lys Gln Asp Val Lys Lys Gly Lys Leu Arg Tyr
65 70 75 80
Val Ala Asn Leu Phe Pro Tyr Lys Gly Tyr Ile Trp Asn Tyr Gly Ala
85 90 95
Ile Pro Gln Thr Trp Glu Asp Pro Gly His Asn Asp Lys His Thr Gly
100 105 110
Cys Cys Gly Asp Asn Asp Pro Ile Asp Val Cys Glu Ile Gly Ser Lys
115 120 125
Val Cys Ala Arg Gly Glu Ile Ile Gly Val Lys Val Leu Gly Ile Leu
130 135 140
Ala Met Ile Asp Glu Gly Glu Thr Asp Trp Lys Val Ile Ala Ile Asn
145 150 155 160
Val Asp Asp Pro Asp Ala Ala Asn Tyr Asn Asp Ile Asn Asp Val Lys
165 170 175
Arg Leu Lys Pro Gly Tyr Leu Glu Ala Thr Val Asp Trp Phe Arg Arg
180 185 190
Tyr Lys Val Pro Asp Gly Lys Pro Glu Asn Glu Phe Ala Phe Asn Ala
195 200 205
Glu Phe Lys Asp Lys Asp Phe Ala Ile Asp Ile Ile Lys Ser Thr His
210 215 220
Asp His Trp Lys Ala Leu Val Thr Lys Lys Thr Asn Gly Lys Gly Ile
225 230 235 240
Ser Cys Met Asn Thr Thr Leu Ser Glu Ser Pro Phe Lys Cys Asp Pro
245 250 255
Asp Ala Ala Arg Ala Ile Val Asp Ala Leu Pro Pro Pro Cys Glu Ser
260 265 270
Ala Cys Thr Val Pro Thr Asp Val Asp Lys Trp Phe His His Gln Lys
275 280 285
Asn
<210> 126
<211> 199
<212> PRT
<213> 智人
<400> 126
Met Ser Ser Gly Asn Ala Lys Ile Gly His Pro Ala Pro Asn Phe Lys
1 5 10 15
Ala Thr Ala Val Met Pro Asp Gly Gln Phe Lys Asp Ile Ser Leu Ser
20 25 30
Asp Tyr Lys Gly Lys Tyr Val Val Phe Phe Phe Tyr Pro Leu Asp Phe
35 40 45
Thr Phe Val Cys Pro Thr Glu Ile Ile Ala Phe Ser Asp Arg Ala Glu
50 55 60
Glu Phe Lys Lys Leu Asn Cys Gln Val Ile Gly Ala Ser Val Asp Ser
65 70 75 80
His Phe Cys His Leu Ala Trp Val Asn Thr Pro Lys Lys Gln Gly Gly
85 90 95
Leu Gly Pro Met Asn Ile Pro Leu Val Ser Asp Pro Lys Arg Thr Ile
100 105 110
Ala Gln Asp Tyr Gly Val Leu Lys Ala Asp Glu Gly Ile Ser Phe Arg
115 120 125
Gly Leu Phe Ile Ile Asp Asp Lys Gly Ile Leu Arg Gln Ile Thr Val
130 135 140
Asn Asp Leu Pro Val Gly Arg Ser Val Asp Glu Thr Leu Arg Leu Val
145 150 155 160
Gln Ala Phe Gln Phe Thr Asp Lys His Gly Glu Val Cys Pro Ala Gly
165 170 175
Trp Lys Pro Gly Ser Asp Thr Ile Lys Pro Asp Val Gln Lys Ser Lys
180 185 190
Glu Tyr Phe Ser Lys Gln Lys
195
<210> 127
<211> 912
<212> PRT
<213> 智人
<400> 127
Met Ser Ala Pro Pro Val Leu Arg Pro Pro Ser Pro Leu Leu Pro Val
1 5 10 15
Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Leu Val Pro Gly Ser Gly
20 25 30
Pro Gly Pro Ala Pro Phe Leu Ala Pro Val Ala Ala Pro Val Gly Gly
35 40 45
Ile Ser Phe His Leu Gln Ile Gly Leu Ser Arg Glu Pro Val Leu Leu
50 55 60
Leu Gln Asp Ser Ser Gly Asp Tyr Ser Leu Ala His Val Arg Glu Met
65 70 75 80
Ala Cys Ser Ile Val Asp Gln Lys Phe Pro Glu Cys Gly Phe Tyr Gly
85 90 95
Met Tyr Asp Lys Ile Leu Leu Phe Arg His Asp Pro Thr Ser Glu Asn
100 105 110
Ile Leu Gln Leu Val Lys Ala Ala Ser Asp Ile Gln Glu Gly Asp Leu
115 120 125
Ile Glu Val Val Leu Ser Ala Ser Ala Thr Phe Glu Asp Phe Gln Ile
130 135 140
Arg Pro His Ala Leu Phe Val His Ser Tyr Arg Ala Pro Ala Phe Cys
145 150 155 160
Asp His Cys Gly Glu Met Leu Trp Gly Leu Val Arg Gln Gly Leu Lys
165 170 175
Cys Glu Gly Cys Gly Leu Asn Tyr His Lys Arg Cys Ala Phe Lys Ile
180 185 190
Pro Asn Asn Cys Ser Gly Val Arg Arg Arg Arg Leu Ser Asn Val Ser
195 200 205
Leu Thr Gly Val Ser Thr Ile Arg Thr Ser Ser Ala Glu Leu Ser Thr
210 215 220
Ser Ala Pro Asp Glu Pro Leu Leu Gln Lys Ser Pro Ser Glu Ser Phe
225 230 235 240
Ile Gly Arg Glu Lys Arg Ser Asn Ser Gln Ser Tyr Ile Gly Arg Pro
245 250 255
Ile His Leu Asp Lys Ile Leu Met Ser Lys Val Lys Val Pro His Thr
260 265 270
Phe Val Ile His Ser Tyr Thr Arg Pro Thr Val Cys Gln Tyr Cys Lys
275 280 285
Lys Leu Leu Lys Gly Leu Phe Arg Gln Gly Leu Gln Cys Lys Asp Cys
290 295 300
Arg Phe Asn Cys His Lys Arg Cys Ala Pro Lys Val Pro Asn Asn Cys
305 310 315 320
Leu Gly Glu Val Thr Ile Asn Gly Asp Leu Leu Ser Pro Gly Ala Glu
325 330 335
Ser Asp Val Val Met Glu Glu Gly Ser Asp Asp Asn Asp Ser Glu Arg
340 345 350
Asn Ser Gly Leu Met Asp Asp Met Glu Glu Ala Met Val Gln Asp Ala
355 360 365
Glu Met Ala Met Ala Glu Cys Gln Asn Asp Ser Gly Glu Met Gln Asp
370 375 380
Pro Asp Pro Asp His Glu Asp Ala Asn Arg Thr Ile Ser Pro Ser Thr
385 390 395 400
Ser Asn Asn Ile Pro Leu Met Arg Val Val Gln Ser Val Lys His Thr
405 410 415
Lys Arg Lys Ser Ser Thr Val Met Lys Glu Gly Trp Met Val His Tyr
420 425 430
Thr Ser Lys Asp Thr Leu Arg Lys Arg His Tyr Trp Arg Leu Asp Ser
435 440 445
Lys Cys Ile Thr Leu Phe Gln Asn Asp Thr Gly Ser Arg Tyr Tyr Lys
450 455 460
Glu Ile Pro Leu Ser Glu Ile Leu Ser Leu Glu Pro Val Lys Thr Ser
465 470 475 480
Ala Leu Ile Pro Asn Gly Ala Asn Pro His Cys Phe Glu Ile Thr Thr
485 490 495
Ala Asn Val Val Tyr Tyr Val Gly Glu Asn Val Val Asn Pro Ser Ser
500 505 510
Pro Ser Pro Asn Asn Ser Val Leu Thr Ser Gly Val Gly Ala Asp Val
515 520 525
Ala Arg Met Trp Glu Ile Ala Ile Gln His Ala Leu Met Pro Val Ile
530 535 540
Pro Lys Gly Ser Ser Val Gly Thr Gly Thr Asn Leu His Arg Asp Ile
545 550 555 560
Ser Val Ser Ile Ser Val Ser Asn Cys Gln Ile Gln Glu Asn Val Asp
565 570 575
Ile Ser Thr Val Tyr Gln Ile Phe Pro Asp Glu Val Leu Gly Ser Gly
580 585 590
Gln Phe Gly Ile Val Tyr Gly Gly Lys His Arg Lys Thr Gly Arg Asp
595 600 605
Val Ala Ile Lys Ile Ile Asp Lys Leu Arg Phe Pro Thr Lys Gln Glu
610 615 620
Ser Gln Leu Arg Asn Glu Val Ala Ile Leu Gln Asn Leu His His Pro
625 630 635 640
Gly Val Val Asn Leu Glu Cys Met Phe Glu Thr Pro Glu Arg Val Phe
645 650 655
Val Val Met Glu Lys Leu His Gly Asp Met Leu Glu Met Ile Leu Ser
660 665 670
Ser Glu Lys Gly Arg Leu Pro Glu His Ile Thr Lys Phe Leu Ile Thr
675 680 685
Gln Ile Leu Val Ala Leu Arg His Leu His Phe Lys Asn Ile Val His
690 695 700
Cys Asp Leu Lys Pro Glu Asn Val Leu Leu Ala Ser Ala Asp Pro Phe
705 710 715 720
Pro Gln Val Lys Leu Cys Asp Phe Gly Phe Ala Arg Ile Ile Gly Glu
725 730 735
Lys Ser Phe Arg Arg Ser Val Val Gly Thr Pro Ala Tyr Leu Ala Pro
740 745 750
Glu Val Leu Arg Asn Lys Gly Tyr Asn Arg Ser Leu Asp Met Trp Ser
755 760 765
Val Gly Val Ile Ile Tyr Val Ser Leu Ser Gly Thr Phe Pro Phe Asn
770 775 780
Glu Asp Glu Asp Ile His Asp Gln Ile Gln Asn Ala Ala Phe Met Tyr
785 790 795 800
Pro Pro Asn Pro Trp Lys Glu Ile Ser His Glu Ala Ile Asp Leu Ile
805 810 815
Asn Asn Leu Leu Gln Val Lys Met Arg Lys Arg Tyr Ser Val Asp Lys
820 825 830
Thr Leu Ser His Pro Trp Leu Gln Asp Tyr Gln Thr Trp Leu Asp Leu
835 840 845
Arg Glu Leu Glu Cys Lys Ile Gly Glu Arg Tyr Ile Thr His Glu Ser
850 855 860
Asp Asp Leu Arg Trp Glu Lys Tyr Ala Gly Glu Gln Gly Leu Gln Tyr
865 870 875 880
Pro Thr His Leu Ile Asn Pro Ser Ala Ser His Ser Asp Thr Pro Glu
885 890 895
Thr Glu Glu Thr Glu Met Lys Ala Leu Gly Glu Arg Val Ser Ile Leu
900 905 910
<210> 128
<211> 227
<212> PRT
<213> 智人
<400> 128
Met Asn Ile Lys Gly Ser Pro Trp Lys Gly Ser Leu Leu Leu Leu Leu
1 5 10 15
Val Ser Asn Leu Leu Leu Cys Gln Ser Val Ala Pro Leu Pro Ile Cys
20 25 30
Pro Gly Gly Ala Ala Arg Cys Gln Val Thr Leu Arg Asp Leu Phe Asp
35 40 45
Arg Ala Val Val Leu Ser His Tyr Ile His Asn Leu Ser Ser Glu Met
50 55 60
Phe Ser Glu Phe Asp Lys Arg Tyr Thr His Gly Arg Gly Phe Ile Thr
65 70 75 80
Lys Ala Ile Asn Ser Cys His Thr Ser Ser Leu Ala Thr Pro Glu Asp
85 90 95
Lys Glu Gln Ala Gln Gln Met Asn Gln Lys Asp Phe Leu Ser Leu Ile
100 105 110
Val Ser Ile Leu Arg Ser Trp Asn Glu Pro Leu Tyr His Leu Val Thr
115 120 125
Glu Val Arg Gly Met Gln Glu Ala Pro Glu Ala Ile Leu Ser Lys Ala
130 135 140
Val Glu Ile Glu Glu Gln Thr Lys Arg Leu Leu Glu Gly Met Glu Leu
145 150 155 160
Ile Val Ser Gln Val His Pro Glu Thr Lys Glu Asn Glu Ile Tyr Pro
165 170 175
Val Trp Ser Gly Leu Pro Ser Leu Gln Met Ala Asp Glu Glu Ser Arg
180 185 190
Leu Ser Ala Tyr Tyr Asn Leu Leu His Cys Leu Arg Arg Asp Ser His
195 200 205
Lys Ile Asp Asn Tyr Leu Lys Leu Leu Lys Cys Arg Ile Ile His Asn
210 215 220
Asn Asn Cys
225
<210> 129
<211> 226
<212> PRT
<213> 智人
<400> 129
Met Phe Thr Leu Leu Val Leu Leu Ser Gln Leu Pro Thr Val Thr Leu
1 5 10 15
Gly Phe Pro His Cys Ala Arg Gly Pro Lys Ala Ser Lys His Ala Gly
20 25 30
Glu Glu Val Phe Thr Ser Lys Glu Glu Ala Asn Phe Phe Ile His Arg
35 40 45
Arg Leu Leu Tyr Asn Arg Phe Asp Leu Glu Leu Phe Thr Pro Gly Asn
50 55 60
Leu Glu Arg Glu Cys Asn Glu Glu Leu Cys Asn Tyr Glu Glu Ala Arg
65 70 75 80
Glu Ile Phe Val Asp Glu Asp Lys Thr Ile Ala Phe Trp Gln Glu Tyr
85 90 95
Ser Ala Lys Gly Pro Thr Thr Lys Ser Asp Gly Asn Arg Glu Lys Ile
100 105 110
Asp Val Met Gly Leu Leu Thr Gly Leu Ile Ala Ala Gly Val Phe Leu
115 120 125
Val Ile Phe Gly Leu Leu Gly Tyr Tyr Leu Cys Ile Thr Lys Cys Asn
130 135 140
Arg Leu Gln His Pro Cys Ser Ser Ala Val Tyr Glu Arg Gly Arg His
145 150 155 160
Thr Pro Ser Ile Ile Phe Arg Arg Pro Glu Glu Ala Ala Leu Ser Pro
165 170 175
Leu Pro Pro Ser Val Glu Asp Ala Gly Leu Pro Ser Tyr Glu Gln Ala
180 185 190
Val Ala Leu Thr Arg Lys His Ser Val Ser Pro Pro Pro Pro Tyr Pro
195 200 205
Gly His Thr Lys Gly Phe Arg Val Phe Lys Lys Ser Met Ser Leu Pro
210 215 220
Ser His
225
<210> 130
<211> 254
<212> PRT
<213> 智人
<400> 130
Met Ala Ser Leu Leu Lys Val Asp Gln Glu Val Lys Leu Lys Val Asp
1 5 10 15
Ser Phe Arg Glu Arg Ile Thr Ser Glu Ala Glu Asp Leu Val Ala Asn
20 25 30
Phe Phe Pro Lys Lys Leu Leu Glu Leu Asp Ser Phe Leu Lys Glu Pro
35 40 45
Ile Leu Asn Ile His Asp Leu Thr Gln Ile His Ser Asp Met Asn Leu
50 55 60
Pro Val Pro Asp Pro Ile Leu Leu Thr Asn Ser His Asp Gly Leu Asp
65 70 75 80
Gly Pro Thr Tyr Lys Lys Arg Arg Leu Asp Glu Cys Glu Glu Ala Phe
85 90 95
Gln Gly Thr Lys Val Phe Val Met Pro Asn Gly Met Leu Lys Ser Asn
100 105 110
Gln Gln Leu Val Asp Ile Ile Glu Lys Val Lys Pro Glu Ile Arg Leu
115 120 125
Leu Ile Glu Lys Cys Asn Thr Val Lys Met Trp Val Gln Leu Leu Ile
130 135 140
Pro Arg Ile Glu Asp Gly Asn Asn Phe Gly Val Ser Ile Gln Glu Glu
145 150 155 160
Thr Val Ala Glu Leu Arg Thr Val Glu Ser Glu Ala Ala Ser Tyr Leu
165 170 175
Asp Gln Ile Ser Arg Tyr Tyr Ile Thr Arg Ala Lys Leu Val Ser Lys
180 185 190
Ile Ala Lys Tyr Pro His Val Glu Asp Tyr Arg Arg Thr Val Thr Glu
195 200 205
Ile Asp Glu Lys Glu Tyr Ile Ser Leu Arg Leu Ile Ile Ser Glu Leu
210 215 220
Arg Asn Gln Tyr Val Thr Leu His Asp Met Ile Leu Lys Asn Ile Glu
225 230 235 240
Lys Ile Lys Arg Pro Arg Ser Ser Asn Ala Glu Thr Leu Tyr
245 250
<210> 131
<211> 403
<212> PRT
<213> 智人
<400> 131
Met Thr Ala Ile Ile Lys Glu Ile Val Ser Arg Asn Lys Arg Arg Tyr
1 5 10 15
Gln Glu Asp Gly Phe Asp Leu Asp Leu Thr Tyr Ile Tyr Pro Asn Ile
20 25 30
Ile Ala Met Gly Phe Pro Ala Glu Arg Leu Glu Gly Val Tyr Arg Asn
35 40 45
Asn Ile Asp Asp Val Val Arg Phe Leu Asp Ser Lys His Lys Asn His
50 55 60
Tyr Lys Ile Tyr Asn Leu Cys Ala Glu Arg His Tyr Asp Thr Ala Lys
65 70 75 80
Phe Asn Cys Arg Val Ala Gln Tyr Pro Phe Glu Asp His Asn Pro Pro
85 90 95
Gln Leu Glu Leu Ile Lys Pro Phe Cys Glu Asp Leu Asp Gln Trp Leu
100 105 110
Ser Glu Asp Asp Asn His Val Ala Ala Ile His Cys Lys Ala Gly Lys
115 120 125
Gly Arg Thr Gly Val Met Ile Cys Ala Tyr Leu Leu His Arg Gly Lys
130 135 140
Phe Leu Lys Ala Gln Glu Ala Leu Asp Phe Tyr Gly Glu Val Arg Thr
145 150 155 160
Arg Asp Lys Lys Gly Val Thr Ile Pro Ser Gln Arg Arg Tyr Val Tyr
165 170 175
Tyr Tyr Ser Tyr Leu Leu Lys Asn His Leu Asp Tyr Arg Pro Val Ala
180 185 190
Leu Leu Phe His Lys Met Met Phe Glu Thr Ile Pro Met Phe Ser Gly
195 200 205
Gly Thr Cys Asn Pro Gln Phe Val Val Cys Gln Leu Lys Val Lys Ile
210 215 220
Tyr Ser Ser Asn Ser Gly Pro Thr Arg Arg Glu Asp Lys Phe Met Tyr
225 230 235 240
Phe Glu Phe Pro Gln Pro Leu Pro Val Cys Gly Asp Ile Lys Val Glu
245 250 255
Phe Phe His Lys Gln Asn Lys Met Leu Lys Lys Asp Lys Met Phe His
260 265 270
Phe Trp Val Asn Thr Phe Phe Ile Pro Gly Pro Glu Glu Thr Ser Glu
275 280 285
Lys Val Glu Asn Gly Ser Leu Cys Asp Gln Glu Ile Asp Ser Ile Cys
290 295 300
Ser Ile Glu Arg Ala Asp Asn Asp Lys Glu Tyr Leu Val Leu Thr Leu
305 310 315 320
Thr Lys Asn Asp Leu Asp Lys Ala Asn Lys Asp Lys Ala Asn Arg Tyr
325 330 335
Phe Ser Pro Asn Phe Lys Val Lys Leu Tyr Phe Thr Lys Thr Val Glu
340 345 350
Glu Pro Ser Asn Pro Glu Ala Ser Ser Ser Thr Ser Val Thr Pro Asp
355 360 365
Val Ser Asp Asn Glu Pro Asp His Tyr Arg Tyr Ser Asp Thr Thr Asp
370 375 380
Ser Asp Pro Glu Asn Glu Pro Phe Asp Glu Asp Gln His Thr Gln Ile
385 390 395 400
Thr Lys Val
<210> 132
<211> 1052
<212> PRT
<213> 智人
<400> 132
Met Ala Ala Ala Tyr Leu Asp Pro Asn Leu Asn His Thr Pro Asn Ser
1 5 10 15
Ser Thr Lys Thr His Leu Gly Thr Gly Met Glu Arg Ser Pro Gly Ala
20 25 30
Met Glu Arg Val Leu Lys Val Phe His Tyr Phe Glu Ser Asn Ser Glu
35 40 45
Pro Thr Thr Trp Ala Ser Ile Ile Arg His Gly Asp Ala Thr Asp Val
50 55 60
Arg Gly Ile Ile Gln Lys Ile Val Asp Ser His Lys Val Lys His Val
65 70 75 80
Ala Cys Tyr Gly Phe Arg Leu Ser His Leu Arg Ser Glu Glu Val His
85 90 95
Trp Leu His Val Asp Met Gly Val Ser Ser Val Arg Glu Lys Tyr Glu
100 105 110
Leu Ala His Pro Pro Glu Glu Trp Lys Tyr Glu Leu Arg Ile Arg Tyr
115 120 125
Leu Pro Lys Gly Phe Leu Asn Gln Phe Thr Glu Asp Lys Pro Thr Leu
130 135 140
Asn Phe Phe Tyr Gln Gln Val Lys Ser Asp Tyr Met Leu Glu Ile Ala
145 150 155 160
Asp Gln Val Asp Gln Glu Ile Ala Leu Lys Leu Gly Cys Leu Glu Ile
165 170 175
Arg Arg Ser Tyr Trp Glu Met Arg Gly Asn Ala Leu Glu Lys Lys Ser
180 185 190
Asn Tyr Glu Val Leu Glu Lys Asp Val Gly Leu Lys Arg Phe Phe Pro
195 200 205
Lys Ser Leu Leu Asp Ser Val Lys Ala Lys Thr Leu Arg Lys Leu Ile
210 215 220
Gln Gln Thr Phe Arg Gln Phe Ala Asn Leu Asn Arg Glu Glu Ser Ile
225 230 235 240
Leu Lys Phe Phe Glu Ile Leu Ser Pro Val Tyr Arg Phe Asp Lys Glu
245 250 255
Cys Phe Lys Cys Ala Leu Gly Ser Ser Trp Ile Ile Ser Val Glu Leu
260 265 270
Ala Ile Gly Pro Glu Glu Gly Ile Ser Tyr Leu Thr Asp Lys Gly Cys
275 280 285
Asn Pro Thr His Leu Ala Asp Phe Thr Gln Val Gln Thr Ile Gln Tyr
290 295 300
Ser Asn Ser Glu Asp Lys Asp Arg Lys Gly Met Leu Gln Leu Lys Ile
305 310 315 320
Ala Gly Ala Pro Glu Pro Leu Thr Val Thr Ala Pro Ser Leu Thr Ile
325 330 335
Ala Glu Asn Met Ala Asp Leu Ile Asp Gly Tyr Cys Arg Leu Val Asn
340 345 350
Gly Thr Ser Gln Ser Phe Ile Ile Arg Pro Gln Lys Glu Gly Glu Arg
355 360 365
Ala Leu Pro Ser Ile Pro Lys Leu Ala Asn Ser Glu Lys Gln Gly Met
370 375 380
Arg Thr His Ala Val Ser Val Ser Glu Thr Asp Asp Tyr Ala Glu Ile
385 390 395 400
Ile Asp Glu Glu Asp Thr Tyr Thr Met Pro Ser Thr Arg Asp Tyr Glu
405 410 415
Ile Gln Arg Glu Arg Ile Glu Leu Gly Arg Cys Ile Gly Glu Gly Gln
420 425 430
Phe Gly Asp Val His Gln Gly Ile Tyr Met Ser Pro Glu Asn Pro Ala
435 440 445
Leu Ala Val Ala Ile Lys Thr Cys Lys Asn Cys Thr Ser Asp Ser Val
450 455 460
Arg Glu Lys Phe Leu Gln Glu Ala Leu Thr Met Arg Gln Phe Asp His
465 470 475 480
Pro His Ile Val Lys Leu Ile Gly Val Ile Thr Glu Asn Pro Val Trp
485 490 495
Ile Ile Met Glu Leu Cys Thr Leu Gly Glu Leu Arg Ser Phe Leu Gln
500 505 510
Val Arg Lys Tyr Ser Leu Asp Leu Ala Ser Leu Ile Leu Tyr Ala Tyr
515 520 525
Gln Leu Ser Thr Ala Leu Ala Tyr Leu Glu Ser Lys Arg Phe Val His
530 535 540
Arg Asp Ile Ala Ala Arg Asn Val Leu Val Ser Ser Asn Asp Cys Val
545 550 555 560
Lys Leu Gly Asp Phe Gly Leu Ser Arg Tyr Met Glu Asp Ser Thr Tyr
565 570 575
Tyr Lys Ala Ser Lys Gly Lys Leu Pro Ile Lys Trp Met Ala Pro Glu
580 585 590
Ser Ile Asn Phe Arg Arg Phe Thr Ser Ala Ser Asp Val Trp Met Phe
595 600 605
Gly Val Cys Met Trp Glu Ile Leu Met His Gly Val Lys Pro Phe Gln
610 615 620
Gly Val Lys Asn Asn Asp Val Ile Gly Arg Ile Glu Asn Gly Glu Arg
625 630 635 640
Leu Pro Met Pro Pro Asn Cys Pro Pro Thr Leu Tyr Ser Leu Met Thr
645 650 655
Lys Cys Trp Ala Tyr Asp Pro Ser Arg Arg Pro Arg Phe Thr Glu Leu
660 665 670
Lys Ala Gln Leu Ser Thr Ile Leu Glu Glu Glu Lys Ala Gln Gln Glu
675 680 685
Glu Arg Met Arg Met Glu Ser Arg Arg Gln Ala Thr Val Ser Trp Asp
690 695 700
Ser Gly Gly Ser Asp Glu Ala Pro Pro Lys Pro Ser Arg Pro Gly Tyr
705 710 715 720
Pro Ser Pro Arg Ser Ser Glu Gly Phe Tyr Pro Ser Pro Gln His Met
725 730 735
Val Gln Thr Asn His Tyr Gln Val Ser Gly Tyr Pro Gly Ser His Gly
740 745 750
Ile Thr Ala Met Ala Gly Ser Ile Tyr Pro Gly Gln Ala Ser Leu Leu
755 760 765
Asp Gln Thr Asp Ser Trp Asn His Arg Pro Gln Glu Ile Ala Met Trp
770 775 780
Gln Pro Asn Val Glu Asp Ser Thr Val Leu Asp Leu Arg Gly Ile Gly
785 790 795 800
Gln Val Leu Pro Thr His Leu Met Glu Glu Arg Leu Ile Arg Gln Gln
805 810 815
Gln Glu Met Glu Glu Asp Gln Arg Trp Leu Glu Lys Glu Glu Arg Phe
820 825 830
Leu Lys Pro Asp Val Arg Leu Ser Arg Gly Ser Ile Asp Arg Glu Asp
835 840 845
Gly Ser Leu Gln Gly Pro Ile Gly Asn Gln His Ile Tyr Gln Pro Val
850 855 860
Gly Lys Pro Asp Pro Ala Ala Pro Pro Lys Lys Pro Pro Arg Pro Gly
865 870 875 880
Ala Pro Gly His Leu Gly Ser Leu Ala Ser Leu Ser Ser Pro Ala Asp
885 890 895
Ser Tyr Asn Glu Gly Val Lys Leu Gln Pro Gln Glu Ile Ser Pro Pro
900 905 910
Pro Thr Ala Asn Leu Asp Arg Ser Asn Asp Lys Val Tyr Glu Asn Val
915 920 925
Thr Gly Leu Val Lys Ala Val Ile Glu Met Ser Ser Lys Ile Gln Pro
930 935 940
Ala Pro Pro Glu Glu Tyr Val Pro Met Val Lys Glu Val Gly Leu Ala
945 950 955 960
Leu Arg Thr Leu Leu Ala Thr Val Asp Glu Thr Ile Pro Leu Leu Pro
965 970 975
Ala Ser Thr His Arg Glu Ile Glu Met Ala Gln Lys Leu Leu Asn Ser
980 985 990
Asp Leu Gly Glu Leu Ile Asn Lys Met Lys Leu Ala Gln Gln Tyr Val
995 1000 1005
Met Thr Ser Leu Gln Gln Glu Tyr Lys Lys Gln Met Leu Thr Ala
1010 1015 1020
Ala His Ala Leu Ala Val Asp Ala Lys Asn Leu Leu Asp Val Ile
1025 1030 1035
Asp Gln Ala Arg Leu Lys Met Leu Gly Gln Thr Arg Pro His
1040 1045 1050
<210> 133
<211> 1009
<212> PRT
<213> 智人
<400> 133
Met Ser Gly Val Ser Glu Pro Leu Ser Arg Val Lys Leu Gly Thr Leu
1 5 10 15
Arg Arg Pro Glu Gly Pro Ala Glu Pro Met Val Val Val Pro Val Asp
20 25 30
Val Glu Lys Glu Asp Val Arg Ile Leu Lys Val Cys Phe Tyr Ser Asn
35 40 45
Ser Phe Asn Pro Gly Lys Asn Phe Lys Leu Val Lys Cys Thr Val Gln
50 55 60
Thr Glu Ile Arg Glu Ile Ile Thr Ser Ile Leu Leu Ser Gly Arg Ile
65 70 75 80
Gly Pro Asn Ile Arg Leu Ala Glu Cys Tyr Gly Leu Arg Leu Lys His
85 90 95
Met Lys Ser Asp Glu Ile His Trp Leu His Pro Gln Met Thr Val Gly
100 105 110
Glu Val Gln Asp Lys Tyr Glu Cys Leu His Val Glu Ala Glu Trp Arg
115 120 125
Tyr Asp Leu Gln Ile Arg Tyr Leu Pro Glu Asp Phe Met Glu Ser Leu
130 135 140
Lys Glu Asp Arg Thr Thr Leu Leu Tyr Phe Tyr Gln Gln Leu Arg Asn
145 150 155 160
Asp Tyr Met Gln Arg Tyr Ala Ser Lys Val Ser Glu Gly Met Ala Leu
165 170 175
Gln Leu Gly Cys Leu Glu Leu Arg Arg Phe Phe Lys Asp Met Pro His
180 185 190
Asn Ala Leu Asp Lys Lys Ser Asn Phe Glu Leu Leu Glu Lys Glu Val
195 200 205
Gly Leu Asp Leu Phe Phe Pro Lys Gln Met Gln Glu Asn Leu Lys Pro
210 215 220
Lys Gln Phe Arg Lys Met Ile Gln Gln Thr Phe Gln Gln Tyr Ala Ser
225 230 235 240
Leu Arg Glu Glu Glu Cys Val Met Lys Phe Phe Asn Thr Leu Ala Gly
245 250 255
Phe Ala Asn Ile Asp Gln Glu Thr Tyr Arg Cys Glu Leu Ile Gln Gly
260 265 270
Trp Asn Ile Thr Val Asp Leu Val Ile Gly Pro Lys Gly Ile Arg Gln
275 280 285
Leu Thr Ser Gln Asp Ala Lys Pro Thr Cys Leu Ala Glu Phe Lys Gln
290 295 300
Ile Arg Ser Ile Arg Cys Leu Pro Leu Glu Glu Gly Gln Ala Val Leu
305 310 315 320
Gln Leu Gly Ile Glu Gly Ala Pro Gln Ala Leu Ser Ile Lys Thr Ser
325 330 335
Ser Leu Ala Glu Ala Glu Asn Met Ala Asp Leu Ile Asp Gly Tyr Cys
340 345 350
Arg Leu Gln Gly Glu His Gln Gly Ser Leu Ile Ile His Pro Arg Lys
355 360 365
Asp Gly Glu Lys Arg Asn Ser Leu Pro Gln Ile Pro Met Leu Asn Leu
370 375 380
Glu Ala Arg Arg Ser His Leu Ser Glu Ser Cys Ser Ile Glu Ser Asp
385 390 395 400
Ile Tyr Ala Glu Ile Pro Asp Glu Thr Leu Arg Arg Pro Gly Gly Pro
405 410 415
Gln Tyr Gly Ile Ala Arg Glu Asp Val Val Leu Asn Arg Ile Leu Gly
420 425 430
Glu Gly Phe Phe Gly Glu Val Tyr Glu Gly Val Tyr Thr Asn His Lys
435 440 445
Gly Glu Lys Ile Asn Val Ala Val Lys Thr Cys Lys Lys Asp Cys Thr
450 455 460
Leu Asp Asn Lys Glu Lys Phe Met Ser Glu Ala Val Ile Met Lys Asn
465 470 475 480
Leu Asp His Pro His Ile Val Lys Leu Ile Gly Ile Ile Glu Glu Glu
485 490 495
Pro Thr Trp Ile Ile Met Glu Leu Tyr Pro Tyr Gly Glu Leu Gly His
500 505 510
Tyr Leu Glu Arg Asn Lys Asn Ser Leu Lys Val Leu Thr Leu Val Leu
515 520 525
Tyr Ser Leu Gln Ile Cys Lys Ala Met Ala Tyr Leu Glu Ser Ile Asn
530 535 540
Cys Val His Arg Asp Ile Ala Val Arg Asn Ile Leu Val Ala Ser Pro
545 550 555 560
Glu Cys Val Lys Leu Gly Asp Phe Gly Leu Ser Arg Tyr Ile Glu Asp
565 570 575
Glu Asp Tyr Tyr Lys Ala Ser Val Thr Arg Leu Pro Ile Lys Trp Met
580 585 590
Ser Pro Glu Ser Ile Asn Phe Arg Arg Phe Thr Thr Ala Ser Asp Val
595 600 605
Trp Met Phe Ala Val Cys Met Trp Glu Ile Leu Ser Phe Gly Lys Gln
610 615 620
Pro Phe Phe Trp Leu Glu Asn Lys Asp Val Ile Gly Val Leu Glu Lys
625 630 635 640
Gly Asp Arg Leu Pro Lys Pro Asp Leu Cys Pro Pro Val Leu Tyr Thr
645 650 655
Leu Met Thr Arg Cys Trp Asp Tyr Asp Pro Ser Asp Arg Pro Arg Phe
660 665 670
Thr Glu Leu Val Cys Ser Leu Ser Asp Val Tyr Gln Met Glu Lys Asp
675 680 685
Ile Ala Met Glu Gln Glu Arg Asn Ala Arg Tyr Arg Thr Pro Lys Ile
690 695 700
Leu Glu Pro Thr Ala Phe Gln Glu Pro Pro Pro Lys Pro Ser Arg Pro
705 710 715 720
Lys Tyr Arg Pro Pro Pro Gln Thr Asn Leu Leu Ala Pro Lys Leu Gln
725 730 735
Phe Gln Val Pro Glu Gly Leu Cys Ala Ser Ser Pro Thr Leu Thr Ser
740 745 750
Pro Met Glu Tyr Pro Ser Pro Val Asn Ser Leu His Thr Pro Pro Leu
755 760 765
His Arg His Asn Val Phe Lys Arg His Ser Met Arg Glu Glu Asp Phe
770 775 780
Ile Gln Pro Ser Ser Arg Glu Glu Ala Gln Gln Leu Trp Glu Ala Glu
785 790 795 800
Lys Val Lys Met Arg Gln Ile Leu Asp Lys Gln Gln Lys Gln Met Val
805 810 815
Glu Asp Tyr Gln Trp Leu Arg Gln Glu Glu Lys Ser Leu Asp Pro Met
820 825 830
Val Tyr Met Asn Asp Lys Ser Pro Leu Thr Pro Glu Lys Glu Val Gly
835 840 845
Tyr Leu Glu Phe Thr Gly Pro Pro Gln Lys Pro Pro Arg Leu Gly Ala
850 855 860
Gln Ser Ile Gln Pro Thr Ala Asn Leu Asp Arg Thr Asp Asp Leu Val
865 870 875 880
Tyr Leu Asn Val Met Glu Leu Val Arg Ala Val Leu Glu Leu Lys Asn
885 890 895
Glu Leu Cys Gln Leu Pro Pro Glu Gly Tyr Val Val Val Val Lys Asn
900 905 910
Val Gly Leu Thr Leu Arg Lys Leu Ile Gly Ser Val Asp Asp Leu Leu
915 920 925
Pro Ser Leu Pro Ser Ser Ser Arg Thr Glu Ile Glu Gly Thr Gln Lys
930 935 940
Leu Leu Asn Lys Asp Leu Ala Glu Leu Ile Asn Lys Met Arg Leu Ala
945 950 955 960
Gln Gln Asn Ala Val Thr Ser Leu Ser Glu Glu Cys Lys Arg Gln Met
965 970 975
Leu Thr Ala Ser His Thr Leu Ala Val Asp Ala Lys Asn Leu Leu Asp
980 985 990
Ala Val Asp Gln Ala Lys Val Leu Ala Asn Leu Ala His Pro Pro Ala
995 1000 1005
Glu
<210> 134
<211> 108
<212> PRT
<213> 智人
<400> 134
Met Ala Ala Ala Met Asp Val Asp Thr Pro Ser Gly Thr Asn Ser Gly
1 5 10 15
Ala Gly Lys Lys Arg Phe Glu Val Lys Lys Trp Asn Ala Val Ala Leu
20 25 30
Trp Ala Trp Asp Ile Val Val Asp Asn Cys Ala Ile Cys Arg Asn His
35 40 45
Ile Met Asp Leu Cys Ile Glu Cys Gln Ala Asn Gln Ala Ser Ala Thr
50 55 60
Ser Glu Glu Cys Thr Val Ala Trp Gly Val Cys Asn His Ala Phe His
65 70 75 80
Phe His Cys Ile Ser Arg Trp Leu Lys Thr Arg Gln Val Cys Pro Leu
85 90 95
Asp Asn Arg Glu Trp Glu Phe Gln Lys Tyr Gly His
100 105
<210> 135
<211> 158
<212> PRT
<213> 智人
<400> 135
Met Ala Ser Arg Ser Met Arg Leu Leu Leu Leu Leu Ser Cys Leu Ala
1 5 10 15
Lys Thr Gly Val Leu Gly Asp Ile Ile Met Arg Pro Ser Cys Ala Pro
20 25 30
Gly Trp Phe Tyr His Lys Ser Asn Cys Tyr Gly Tyr Phe Arg Lys Leu
35 40 45
Arg Asn Trp Ser Asp Ala Glu Leu Glu Cys Gln Ser Tyr Gly Asn Gly
50 55 60
Ala His Leu Ala Ser Ile Leu Ser Leu Lys Glu Ala Ser Thr Ile Ala
65 70 75 80
Glu Tyr Ile Ser Gly Tyr Gln Arg Ser Gln Pro Ile Trp Ile Gly Leu
85 90 95
His Asp Pro Gln Lys Arg Gln Gln Trp Gln Trp Ile Asp Gly Ala Met
100 105 110
Tyr Leu Tyr Arg Ser Trp Ser Gly Lys Ser Met Gly Gly Asn Lys His
115 120 125
Cys Ala Glu Met Ser Ser Asn Asn Asn Phe Leu Thr Trp Ser Ser Asn
130 135 140
Glu Cys Asn Lys Arg Gln His Phe Leu Cys Lys Tyr Arg Pro
145 150 155
<210> 136
<211> 193
<212> PRT
<213> 智人
<400> 136
Met Ala Ala Ile Arg Lys Lys Leu Val Ile Val Gly Asp Gly Ala Cys
1 5 10 15
Gly Lys Thr Cys Leu Leu Ile Val Phe Ser Lys Asp Gln Phe Pro Glu
20 25 30
Val Tyr Val Pro Thr Val Phe Glu Asn Tyr Val Ala Asp Ile Glu Val
35 40 45
Asp Gly Lys Gln Val Glu Leu Ala Leu Trp Asp Thr Ala Gly Gln Glu
50 55 60
Asp Tyr Asp Arg Leu Arg Pro Leu Ser Tyr Pro Asp Thr Asp Val Ile
65 70 75 80
Leu Met Cys Phe Ser Ile Asp Ser Pro Asp Ser Leu Glu Asn Ile Pro
85 90 95
Glu Lys Trp Thr Pro Glu Val Lys His Phe Cys Pro Asn Val Pro Ile
100 105 110
Ile Leu Val Gly Asn Lys Lys Asp Leu Arg Asn Asp Glu His Thr Arg
115 120 125
Arg Glu Leu Ala Lys Met Lys Gln Glu Pro Val Lys Pro Glu Glu Gly
130 135 140
Arg Asp Met Ala Asn Arg Ile Gly Ala Phe Gly Tyr Met Glu Cys Ser
145 150 155 160
Ala Lys Thr Lys Asp Gly Val Arg Glu Val Phe Glu Met Ala Thr Arg
165 170 175
Ala Ala Leu Gln Ala Arg Arg Gly Lys Lys Lys Ser Gly Cys Leu Val
180 185 190
Leu
<210> 137
<211> 196
<212> PRT
<213> 智人
<400> 137
Met Ala Ala Ile Arg Lys Lys Leu Val Val Val Gly Asp Gly Ala Cys
1 5 10 15
Gly Lys Thr Cys Leu Leu Ile Val Phe Ser Lys Asp Glu Phe Pro Glu
20 25 30
Val Tyr Val Pro Thr Val Phe Glu Asn Tyr Val Ala Asp Ile Glu Val
35 40 45
Asp Gly Lys Gln Val Glu Leu Ala Leu Trp Asp Thr Ala Gly Gln Glu
50 55 60
Asp Tyr Asp Arg Leu Arg Pro Leu Ser Tyr Pro Asp Thr Asp Val Ile
65 70 75 80
Leu Met Cys Phe Ser Val Asp Ser Pro Asp Ser Leu Glu Asn Ile Pro
85 90 95
Glu Lys Trp Val Pro Glu Val Lys His Phe Cys Pro Asn Val Pro Ile
100 105 110
Ile Leu Val Ala Asn Lys Lys Asp Leu Arg Ser Asp Glu His Val Arg
115 120 125
Thr Glu Leu Ala Arg Met Lys Gln Glu Pro Val Arg Thr Asp Asp Gly
130 135 140
Arg Ala Met Ala Val Arg Ile Gln Ala Tyr Asp Tyr Leu Glu Cys Ser
145 150 155 160
Ala Lys Thr Lys Glu Gly Val Arg Glu Val Phe Glu Thr Ala Thr Arg
165 170 175
Ala Ala Leu Gln Lys Arg Tyr Gly Ser Gln Asn Gly Cys Ile Asn Cys
180 185 190
Cys Lys Val Leu
195
<210> 138
<211> 193
<212> PRT
<213> 智人
<400> 138
Met Ala Ala Ile Arg Lys Lys Leu Val Ile Val Gly Asp Gly Ala Cys
1 5 10 15
Gly Lys Thr Cys Leu Leu Ile Val Phe Ser Lys Asp Gln Phe Pro Glu
20 25 30
Val Tyr Val Pro Thr Val Phe Glu Asn Tyr Ile Ala Asp Ile Glu Val
35 40 45
Asp Gly Lys Gln Val Glu Leu Ala Leu Trp Asp Thr Ala Gly Gln Glu
50 55 60
Asp Tyr Asp Arg Leu Arg Pro Leu Ser Tyr Pro Asp Thr Asp Val Ile
65 70 75 80
Leu Met Cys Phe Ser Ile Asp Ser Pro Asp Ser Leu Glu Asn Ile Pro
85 90 95
Glu Lys Trp Thr Pro Glu Val Lys His Phe Cys Pro Asn Val Pro Ile
100 105 110
Ile Leu Val Gly Asn Lys Lys Asp Leu Arg Gln Asp Glu His Thr Arg
115 120 125
Arg Glu Leu Ala Lys Met Lys Gln Glu Pro Val Arg Ser Glu Glu Gly
130 135 140
Arg Asp Met Ala Asn Arg Ile Ser Ala Phe Gly Tyr Leu Glu Cys Ser
145 150 155 160
Ala Lys Thr Lys Glu Gly Val Arg Glu Val Phe Glu Met Ala Thr Arg
165 170 175
Ala Gly Leu Gln Val Arg Lys Asn Lys Arg Arg Arg Gly Cys Pro Ile
180 185 190
Leu
<210> 139
<211> 295
<212> PRT
<213> 智人
<400> 139
Met Ser Gly Ala Leu Asp Val Leu Gln Met Lys Glu Glu Asp Val Leu
1 5 10 15
Lys Phe Leu Ala Ala Gly Thr His Leu Gly Gly Thr Asn Leu Asp Phe
20 25 30
Gln Met Glu Gln Tyr Ile Tyr Lys Arg Lys Ser Asp Gly Ile Tyr Ile
35 40 45
Ile Asn Leu Lys Arg Thr Trp Glu Lys Leu Leu Leu Ala Ala Arg Ala
50 55 60
Ile Val Ala Ile Glu Asn Pro Ala Asp Val Ser Val Ile Ser Ser Arg
65 70 75 80
Asn Thr Gly Gln Arg Ala Val Leu Lys Phe Ala Ala Ala Thr Gly Ala
85 90 95
Thr Pro Ile Ala Gly Arg Phe Thr Pro Gly Thr Phe Thr Asn Gln Ile
100 105 110
Gln Ala Ala Phe Arg Glu Pro Arg Leu Leu Val Val Thr Asp Pro Arg
115 120 125
Ala Asp His Gln Pro Leu Thr Glu Ala Ser Tyr Val Asn Leu Pro Thr
130 135 140
Ile Ala Leu Cys Asn Thr Asp Ser Pro Leu Arg Tyr Val Asp Ile Ala
145 150 155 160
Ile Pro Cys Asn Asn Lys Gly Ala His Ser Val Gly Leu Met Trp Trp
165 170 175
Met Leu Ala Arg Glu Val Leu Arg Met Arg Gly Thr Ile Ser Arg Glu
180 185 190
His Pro Trp Glu Val Met Pro Asp Leu Tyr Phe Tyr Arg Asp Pro Glu
195 200 205
Glu Ile Glu Lys Glu Glu Gln Ala Ala Ala Glu Lys Ala Val Thr Lys
210 215 220
Glu Glu Phe Gln Gly Glu Trp Thr Ala Pro Ala Pro Glu Phe Thr Ala
225 230 235 240
Thr Gln Pro Glu Val Ala Asp Trp Ser Glu Gly Val Gln Val Pro Ser
245 250 255
Val Pro Ile Gln Gln Phe Pro Thr Glu Asp Trp Ser Ala Gln Pro Ala
260 265 270
Thr Glu Asp Trp Ser Ala Ala Pro Thr Ala Gln Ala Thr Glu Trp Val
275 280 285
Gly Ala Thr Thr Asp Trp Ser
290 295
<210> 140
<211> 1410
<212> PRT
<213> 智人
<400> 140
Met Asp Ile Tyr Asp Thr Gln Thr Leu Gly Val Val Val Phe Gly Gly
1 5 10 15
Phe Met Val Val Ser Ala Ile Gly Ile Phe Leu Val Ser Thr Phe Ser
20 25 30
Met Lys Glu Thr Ser Tyr Glu Glu Ala Leu Ala Asn Gln Arg Lys Glu
35 40 45
Met Ala Lys Thr His His Gln Lys Val Glu Lys Lys Lys Lys Glu Lys
50 55 60
Thr Val Glu Lys Lys Gly Lys Thr Lys Lys Lys Glu Glu Lys Pro Asn
65 70 75 80
Gly Lys Ile Pro Asp His Asp Pro Ala Pro Asn Val Thr Val Leu Leu
85 90 95
Arg Glu Pro Val Arg Ala Pro Ala Val Ala Val Ala Pro Thr Pro Val
100 105 110
Gln Pro Pro Ile Ile Val Ala Pro Val Ala Thr Val Pro Ala Met Pro
115 120 125
Gln Glu Lys Leu Ala Ser Ser Pro Lys Asp Lys Lys Lys Lys Glu Lys
130 135 140
Lys Val Ala Lys Val Glu Pro Ala Val Ser Ser Val Val Asn Ser Ile
145 150 155 160
Gln Val Leu Thr Ser Lys Ala Ala Ile Leu Glu Thr Ala Pro Lys Glu
165 170 175
Val Pro Met Val Val Val Pro Pro Val Gly Ala Lys Gly Asn Thr Pro
180 185 190
Ala Thr Gly Thr Thr Gln Gly Lys Lys Ala Glu Gly Thr Gln Asn Gln
195 200 205
Ser Lys Lys Ala Glu Gly Ala Pro Asn Gln Gly Arg Lys Ala Glu Gly
210 215 220
Thr Pro Asn Gln Gly Lys Lys Thr Glu Gly Thr Pro Asn Gln Gly Lys
225 230 235 240
Lys Ala Glu Gly Thr Pro Asn Gln Gly Lys Lys Ala Glu Gly Thr Pro
245 250 255
Asn Gln Gly Lys Lys Ala Glu Gly Ala Gln Asn Gln Gly Lys Lys Val
260 265 270
Asp Thr Thr Pro Asn Gln Gly Lys Lys Val Glu Gly Ala Pro Thr Gln
275 280 285
Gly Arg Lys Ala Glu Gly Ala Gln Asn Gln Ala Lys Lys Val Glu Gly
290 295 300
Ala Gln Asn Gln Gly Lys Lys Ala Glu Gly Ala Gln Asn Gln Gly Lys
305 310 315 320
Lys Gly Glu Gly Ala Gln Asn Gln Gly Lys Lys Ala Glu Gly Ala Gln
325 330 335
Asn Gln Gly Lys Lys Ala Glu Gly Ala Gln Asn Gln Gly Lys Lys Ala
340 345 350
Glu Gly Ala Gln Asn Gln Gly Lys Lys Ala Glu Gly Ala Gln Asn Gln
355 360 365
Gly Lys Lys Ala Glu Gly Ala Gln Asn Gln Gly Lys Lys Ser Glu Gly
370 375 380
Ala Gln Asn Gln Gly Lys Lys Val Glu Gly Ala Gln Asn Gln Gly Lys
385 390 395 400
Lys Ala Glu Gly Ala Gln Asn Gln Gly Lys Lys Ala Glu Gly Ala Gln
405 410 415
Asn Gln Gly Lys Lys Ala Glu Gly Ala Gln Asn Gln Gly Lys Lys Ala
420 425 430
Glu Gly Ala Gln Asn Gln Gly Lys Lys Ala Glu Gly Ala Gln Asn Gln
435 440 445
Gly Lys Lys Ala Glu Gly Ala Gln Asn Gln Gly Lys Lys Ala Glu Gly
450 455 460
Ala Gln Asn Gln Gly Lys Lys Val Glu Gly Ala Gln Asn Gln Gly Lys
465 470 475 480
Lys Ala Glu Gly Ala Gln Asn Gln Gly Lys Lys Ala Glu Gly Ala Gln
485 490 495
Asn Gln Gly Lys Lys Ala Glu Gly Ala Gln Asn Gln Gly Gln Lys Gly
500 505 510
Glu Gly Ala Gln Asn Gln Gly Lys Lys Thr Glu Gly Ala Gln Gly Lys
515 520 525
Lys Ala Glu Arg Ser Pro Asn Gln Gly Lys Lys Gly Glu Gly Ala Pro
530 535 540
Ile Gln Gly Lys Lys Ala Asp Ser Val Ala Asn Gln Gly Thr Lys Val
545 550 555 560
Glu Gly Ile Thr Asn Gln Gly Lys Lys Ala Glu Gly Ser Pro Ser Glu
565 570 575
Gly Lys Lys Ala Glu Gly Ser Pro Asn Gln Gly Lys Lys Ala Asp Ala
580 585 590
Ala Ala Asn Gln Gly Lys Lys Thr Glu Ser Ala Ser Val Gln Gly Arg
595 600 605
Asn Thr Asp Val Ala Gln Ser Pro Glu Ala Pro Lys Gln Glu Ala Pro
610 615 620
Ala Lys Lys Lys Ser Gly Ser Lys Lys Lys Gly Glu Pro Gly Pro Pro
625 630 635 640
Asp Ala Asp Gly Pro Leu Tyr Leu Pro Tyr Lys Thr Leu Val Ser Thr
645 650 655
Val Gly Ser Met Val Phe Asn Glu Gly Glu Ala Gln Arg Leu Ile Glu
660 665 670
Ile Leu Ser Glu Lys Ala Gly Ile Ile Gln Asp Thr Trp His Lys Ala
675 680 685
Thr Gln Lys Gly Asp Pro Val Ala Ile Leu Lys Arg Gln Leu Glu Glu
690 695 700
Lys Glu Lys Leu Leu Ala Thr Glu Gln Glu Asp Ala Ala Val Ala Lys
705 710 715 720
Ser Lys Leu Arg Glu Leu Asn Lys Glu Met Ala Ala Glu Lys Ala Lys
725 730 735
Ala Ala Ala Gly Glu Ala Lys Val Lys Lys Gln Leu Val Ala Arg Glu
740 745 750
Gln Glu Ile Thr Ala Val Gln Ala Arg Met Gln Ala Ser Tyr Arg Glu
755 760 765
His Val Lys Glu Val Gln Gln Leu Gln Gly Lys Ile Arg Thr Leu Gln
770 775 780
Glu Gln Leu Glu Asn Gly Pro Asn Thr Gln Leu Ala Arg Leu Gln Gln
785 790 795 800
Glu Asn Ser Ile Leu Arg Asp Ala Leu Asn Gln Ala Thr Ser Gln Val
805 810 815
Glu Ser Lys Gln Asn Ala Glu Leu Ala Lys Leu Arg Gln Glu Leu Ser
820 825 830
Lys Val Ser Lys Glu Leu Val Glu Lys Ser Glu Ala Val Arg Gln Asp
835 840 845
Glu Gln Gln Arg Lys Ala Leu Glu Ala Lys Ala Ala Ala Phe Glu Lys
850 855 860
Gln Val Leu Gln Leu Gln Ala Ser His Arg Glu Ser Glu Glu Ala Leu
865 870 875 880
Gln Lys Arg Leu Asp Glu Val Ser Arg Glu Leu Cys His Thr Gln Ser
885 890 895
Ser His Ala Ser Leu Arg Ala Asp Ala Glu Lys Ala Gln Glu Gln Gln
900 905 910
Gln Gln Met Ala Glu Leu His Ser Lys Leu Gln Ser Ser Glu Ala Glu
915 920 925
Val Arg Ser Lys Cys Glu Glu Leu Ser Gly Leu His Gly Gln Leu Gln
930 935 940
Glu Ala Arg Ala Glu Asn Ser Gln Leu Thr Glu Arg Ile Arg Ser Ile
945 950 955 960
Glu Ala Leu Leu Glu Ala Gly Gln Ala Arg Asp Ala Gln Asp Val Gln
965 970 975
Ala Ser Gln Ala Glu Ala Asp Gln Gln Gln Thr Arg Leu Lys Glu Leu
980 985 990
Glu Ser Gln Val Ser Gly Leu Glu Lys Glu Ala Ile Glu Leu Arg Glu
995 1000 1005
Ala Val Glu Gln Gln Lys Val Lys Asn Asn Asp Leu Arg Glu Lys
1010 1015 1020
Asn Trp Lys Ala Met Glu Ala Leu Ala Thr Ala Glu Gln Ala Cys
1025 1030 1035
Lys Glu Lys Leu Leu Ser Leu Thr Gln Ala Lys Glu Glu Ser Glu
1040 1045 1050
Lys Gln Leu Cys Leu Ile Glu Ala Gln Thr Met Glu Ala Leu Leu
1055 1060 1065
Ala Leu Leu Pro Glu Leu Ser Val Leu Ala Gln Gln Asn Tyr Thr
1070 1075 1080
Glu Trp Leu Gln Asp Leu Lys Glu Lys Gly Pro Thr Leu Leu Lys
1085 1090 1095
His Pro Pro Ala Pro Ala Glu Pro Ser Ser Asp Leu Ala Ser Lys
1100 1105 1110
Leu Arg Glu Ala Glu Glu Thr Gln Ser Thr Leu Gln Ala Glu Cys
1115 1120 1125
Asp Gln Tyr Arg Ser Ile Leu Ala Glu Thr Glu Gly Met Leu Arg
1130 1135 1140
Asp Leu Gln Lys Ser Val Glu Glu Glu Glu Gln Val Trp Arg Ala
1145 1150 1155
Lys Val Gly Ala Ala Glu Glu Glu Leu Gln Lys Ser Arg Val Thr
1160 1165 1170
Val Lys His Leu Glu Glu Ile Val Glu Lys Leu Lys Gly Glu Leu
1175 1180 1185
Glu Ser Ser Asp Gln Val Arg Glu His Thr Ser His Leu Glu Ala
1190 1195 1200
Glu Leu Glu Lys His Met Ala Ala Ala Ser Ala Glu Cys Gln Asn
1205 1210 1215
Tyr Ala Lys Glu Val Ala Gly Leu Arg Gln Leu Leu Leu Glu Ser
1220 1225 1230
Gln Ser Gln Leu Asp Ala Ala Lys Ser Glu Ala Gln Lys Gln Ser
1235 1240 1245
Asp Glu Leu Ala Leu Val Arg Gln Gln Leu Ser Glu Met Lys Ser
1250 1255 1260
His Val Glu Asp Gly Asp Ile Ala Gly Ala Pro Ala Ser Ser Pro
1265 1270 1275
Glu Ala Pro Pro Ala Glu Gln Asp Pro Val Gln Leu Lys Thr Gln
1280 1285 1290
Leu Glu Trp Thr Glu Ala Ile Leu Glu Asp Glu Gln Thr Gln Arg
1295 1300 1305
Gln Lys Leu Thr Ala Glu Phe Glu Glu Ala Gln Thr Ser Ala Cys
1310 1315 1320
Arg Leu Gln Glu Glu Leu Glu Lys Leu Arg Thr Ala Gly Pro Leu
1325 1330 1335
Glu Ser Ser Glu Thr Glu Glu Ala Ser Gln Leu Lys Glu Arg Leu
1340 1345 1350
Glu Lys Glu Lys Lys Leu Thr Ser Asp Leu Gly Arg Ala Ala Thr
1355 1360 1365
Arg Leu Gln Glu Leu Leu Lys Thr Thr Gln Glu Gln Leu Ala Arg
1370 1375 1380
Glu Lys Asp Thr Val Lys Lys Leu Gln Glu Gln Leu Glu Lys Ala
1385 1390 1395
Glu Asp Gly Ser Ser Ser Lys Glu Gly Thr Ser Val
1400 1405 1410
<210> 141
<211> 105
<212> PRT
<213> 智人
<400> 141
Met Ala Lys Ile Ser Ser Pro Thr Glu Thr Glu Arg Cys Ile Glu Ser
1 5 10 15
Leu Ile Ala Val Phe Gln Lys Tyr Ala Gly Lys Asp Gly Tyr Asn Tyr
20 25 30
Thr Leu Ser Lys Thr Glu Phe Leu Ser Phe Met Asn Thr Glu Leu Ala
35 40 45
Ala Phe Thr Lys Asn Gln Lys Asp Pro Gly Val Leu Asp Arg Met Met
50 55 60
Lys Lys Leu Asp Thr Asn Ser Asp Gly Gln Leu Asp Phe Ser Glu Phe
65 70 75 80
Leu Asn Leu Ile Gly Gly Leu Ala Met Ala Cys His Asp Ser Phe Leu
85 90 95
Lys Ala Val Pro Ser Gln Lys Arg Thr
100 105
<210> 142
<211> 92
<212> PRT
<213> 智人
<400> 142
Met Thr Lys Leu Glu Glu His Leu Glu Gly Ile Val Asn Ile Phe His
1 5 10 15
Gln Tyr Ser Val Arg Lys Gly His Phe Asp Thr Leu Ser Lys Gly Glu
20 25 30
Leu Lys Gln Leu Leu Thr Lys Glu Leu Ala Asn Thr Ile Lys Asn Ile
35 40 45
Lys Asp Lys Ala Val Ile Asp Glu Ile Phe Gln Gly Leu Asp Ala Asn
50 55 60
Gln Asp Glu Gln Val Asp Phe Gln Glu Phe Ile Ser Leu Val Ala Ile
65 70 75 80
Ala Leu Lys Ala Ala His Tyr His Thr His Lys Glu
85 90
<210> 143
<211> 93
<212> PRT
<213> 智人
<400> 143
Met Leu Thr Glu Leu Glu Lys Ala Leu Asn Ser Ile Ile Asp Val Tyr
1 5 10 15
His Lys Tyr Ser Leu Ile Lys Gly Asn Phe His Ala Val Tyr Arg Asp
20 25 30
Asp Leu Lys Lys Leu Leu Glu Thr Glu Cys Pro Gln Tyr Ile Arg Lys
35 40 45
Lys Gly Ala Asp Val Trp Phe Lys Glu Leu Asp Ile Asn Thr Asp Gly
50 55 60
Ala Val Asn Phe Gln Glu Phe Leu Ile Leu Val Ile Lys Met Gly Val
65 70 75 80
Ala Ala His Lys Lys Ser His Glu Glu Ser His Lys Glu
85 90
<210> 144
<211> 114
<212> PRT
<213> 智人
<400> 144
Met Thr Cys Lys Met Ser Gln Leu Glu Arg Asn Ile Glu Thr Ile Ile
1 5 10 15
Asn Thr Phe His Gln Tyr Ser Val Lys Leu Gly His Pro Asp Thr Leu
20 25 30
Asn Gln Gly Glu Phe Lys Glu Leu Val Arg Lys Asp Leu Gln Asn Phe
35 40 45
Leu Lys Lys Glu Asn Lys Asn Glu Lys Val Ile Glu His Ile Met Glu
50 55 60
Asp Leu Asp Thr Asn Ala Asp Lys Gln Leu Ser Phe Glu Glu Phe Ile
65 70 75 80
Met Leu Met Ala Arg Leu Thr Trp Ala Ser His Glu Lys Met His Glu
85 90 95
Gly Asp Glu Gly Pro Gly His His His Lys Pro Gly Leu Gly Glu Gly
100 105 110
Thr Pro
<210> 145
<211> 122
<212> PRT
<213> 智人
<400> 145
Met Lys Leu Leu Thr Gly Leu Val Phe Cys Ser Leu Val Leu Gly Val
1 5 10 15
Ser Ser Arg Ser Phe Phe Ser Phe Leu Gly Glu Ala Phe Asp Gly Ala
20 25 30
Arg Asp Met Trp Arg Ala Tyr Ser Asp Met Arg Glu Ala Asn Tyr Ile
35 40 45
Gly Ser Asp Lys Tyr Phe His Ala Arg Gly Asn Tyr Asp Ala Ala Lys
50 55 60
Arg Gly Pro Gly Gly Val Trp Ala Ala Glu Ala Ile Ser Asp Ala Arg
65 70 75 80
Glu Asn Ile Gln Arg Phe Phe Gly His Gly Ala Glu Asp Ser Leu Ala
85 90 95
Asp Gln Ala Ala Asn Glu Trp Gly Arg Ser Gly Lys Asp Pro Asn His
100 105 110
Phe Arg Pro Ala Gly Leu Pro Glu Lys Tyr
115 120
<210> 146
<211> 122
<212> PRT
<213> 智人
<400> 146
Met Lys Leu Leu Thr Gly Leu Val Phe Cys Ser Leu Val Leu Ser Val
1 5 10 15
Ser Ser Arg Ser Phe Phe Ser Phe Leu Gly Glu Ala Phe Asp Gly Ala
20 25 30
Arg Asp Met Trp Arg Ala Tyr Ser Asp Met Arg Glu Ala Asn Tyr Ile
35 40 45
Gly Ser Asp Lys Tyr Phe His Ala Arg Gly Asn Tyr Asp Ala Ala Lys
50 55 60
Arg Gly Pro Gly Gly Ala Trp Ala Ala Glu Val Ile Ser Asn Ala Arg
65 70 75 80
Glu Asn Ile Gln Arg Leu Thr Gly Arg Gly Ala Glu Asp Ser Leu Ala
85 90 95
Asp Gln Ala Ala Asn Lys Trp Gly Arg Ser Gly Arg Asp Pro Asn His
100 105 110
Phe Arg Pro Ala Gly Leu Pro Glu Lys Tyr
115 120
<210> 147
<211> 276
<212> PRT
<213> 智人
<400> 147
Met Asp Ser Ser Arg Glu Pro Thr Leu Gly Arg Leu Asp Ala Ala Gly
1 5 10 15
Phe Trp Gln Val Trp Gln Arg Phe Asp Ala Asp Glu Lys Gly Tyr Ile
20 25 30
Glu Glu Lys Glu Leu Asp Ala Phe Phe Leu His Met Leu Met Lys Leu
35 40 45
Gly Thr Asp Asp Thr Val Met Lys Ala Asn Leu His Lys Val Lys Gln
50 55 60
Gln Phe Met Thr Thr Gln Asp Ala Ser Lys Asp Gly Arg Ile Arg Met
65 70 75 80
Lys Glu Leu Ala Gly Met Phe Leu Ser Glu Asp Glu Asn Phe Leu Leu
85 90 95
Leu Phe Arg Arg Glu Asn Pro Leu Asp Ser Ser Val Glu Phe Met Gln
100 105 110
Ile Trp Arg Lys Tyr Asp Ala Asp Ser Ser Gly Phe Ile Ser Ala Ala
115 120 125
Glu Leu Arg Asn Phe Leu Arg Asp Leu Phe Leu His His Lys Lys Ala
130 135 140
Ile Ser Glu Ala Lys Leu Glu Glu Tyr Thr Gly Thr Met Met Lys Ile
145 150 155 160
Phe Asp Arg Asn Lys Asp Gly Arg Leu Asp Leu Asn Asp Leu Ala Arg
165 170 175
Ile Leu Ala Leu Gln Glu Asn Phe Leu Leu Gln Phe Lys Met Asp Ala
180 185 190
Cys Ser Thr Glu Glu Arg Lys Arg Asp Phe Glu Lys Ile Phe Ala Tyr
195 200 205
Tyr Asp Val Ser Lys Thr Gly Ala Leu Glu Gly Pro Glu Val Asp Gly
210 215 220
Phe Val Lys Asp Met Met Glu Leu Val Gln Pro Ser Ile Ser Gly Val
225 230 235 240
Asp Leu Asp Lys Phe Arg Glu Ile Leu Leu Arg His Cys Asp Val Asn
245 250 255
Lys Asp Gly Lys Ile Gln Lys Ser Glu Leu Ala Leu Cys Leu Gly Leu
260 265 270
Lys Ile Asn Pro
275
<210> 148
<211> 435
<212> PRT
<213> 智人
<400> 148
Met Ser Gly Tyr Gln Arg Arg Pro Gly Ala Thr Pro Leu Ser Arg Ala
1 5 10 15
Arg Ser Leu Ala Ile Pro Asp Ala Pro Ala Phe Tyr Glu Arg Arg Ser
20 25 30
Cys Leu Pro Gln Leu Asn Cys Glu Arg Pro His Gly Arg Asp Leu Asp
35 40 45
Ser Pro Phe Phe Gly Ile Arg Pro Ala Phe Met Cys Tyr Val Pro Ser
50 55 60
Pro Val Leu Ala Ser Val Gly Asp Thr Asp Phe Gly Tyr Gly Lys Gly
65 70 75 80
Lys Cys Ser Lys Gln Ser Pro Ser Gly Ala His Gly Thr His Phe Gly
85 90 95
Asp Asp Arg Phe Glu Asp Leu Glu Glu Ala Asn Pro Phe Ser Phe Arg
100 105 110
Glu Phe Leu Lys Thr Lys Asn Leu Gly Leu Ser Lys Glu Asp Pro Ala
115 120 125
Ser Arg Ile Tyr Ala Lys Glu Ala Ser Arg His Ser Leu Gly Leu Asp
130 135 140
His Asn Ser Pro Pro Ser Gln Thr Gly Gly Tyr Gly Leu Glu Tyr Gln
145 150 155 160
Gln Pro Phe Phe Glu Asp Pro Thr Gly Ala Gly Asp Leu Leu Asp Glu
165 170 175
Glu Glu Asp Glu Asp Thr Gly Trp Ser Gly Ala Tyr Leu Pro Ser Ala
180 185 190
Ile Glu Gln Thr His Pro Glu Arg Val Pro Ala Gly Thr Ser Pro Cys
195 200 205
Ser Thr Tyr Leu Ser Phe Phe Ser Thr Pro Ser Glu Leu Ala Gly Pro
210 215 220
Glu Ser Leu Pro Ser Trp Ala Leu Ser Asp Thr Asp Ser Arg Val Ser
225 230 235 240
Pro Ala Ser Pro Ala Gly Ser Pro Ser Ala Asp Phe Ala Val His Gly
245 250 255
Glu Ser Leu Gly Asp Arg His Leu Arg Thr Leu Gln Ile Ser Tyr Asp
260 265 270
Ala Leu Lys Asp Glu Asn Ser Lys Leu Arg Arg Lys Leu Asn Glu Val
275 280 285
Gln Ser Phe Ser Glu Ala Gln Thr Glu Met Val Arg Thr Leu Glu Arg
290 295 300
Lys Leu Glu Ala Lys Met Ile Lys Glu Glu Ser Asp Tyr His Asp Leu
305 310 315 320
Glu Ser Val Val Gln Gln Val Glu Gln Asn Leu Glu Leu Met Thr Lys
325 330 335
Arg Ala Val Lys Ala Glu Asn His Val Val Lys Leu Lys Gln Glu Ile
340 345 350
Ser Leu Leu Gln Ala Gln Val Ser Asn Phe Gln Arg Glu Asn Glu Ala
355 360 365
Leu Arg Cys Gly Gln Gly Ala Ser Leu Thr Val Val Lys Gln Asn Ala
370 375 380
Asp Val Ala Leu Gln Asn Leu Arg Val Val Met Asn Ser Ala Gln Ala
385 390 395 400
Ser Ile Lys Gln Leu Val Ser Gly Ala Glu Thr Leu Asn Leu Val Ala
405 410 415
Glu Ile Leu Lys Ser Ile Asp Arg Ile Ser Glu Val Lys Asp Glu Glu
420 425 430
Glu Asp Ser
435
<210> 149
<211> 664
<212> PRT
<213> 智人
<400> 149
Met Ser Gly Val Arg Gly Leu Ser Arg Leu Leu Ser Ala Arg Arg Leu
1 5 10 15
Ala Leu Ala Lys Ala Trp Pro Thr Val Leu Gln Thr Gly Thr Arg Gly
20 25 30
Phe His Phe Thr Val Asp Gly Asn Lys Arg Ala Ser Ala Lys Val Ser
35 40 45
Asp Ser Ile Ser Ala Gln Tyr Pro Val Val Asp His Glu Phe Asp Ala
50 55 60
Val Val Val Gly Ala Gly Gly Ala Gly Leu Arg Ala Ala Phe Gly Leu
65 70 75 80
Ser Glu Ala Gly Phe Asn Thr Ala Cys Val Thr Lys Leu Phe Pro Thr
85 90 95
Arg Ser His Thr Val Ala Ala Gln Gly Gly Ile Asn Ala Ala Leu Gly
100 105 110
Asn Met Glu Glu Asp Asn Trp Arg Trp His Phe Tyr Asp Thr Val Lys
115 120 125
Gly Ser Asp Trp Leu Gly Asp Gln Asp Ala Ile His Tyr Met Thr Glu
130 135 140
Gln Ala Pro Ala Ala Val Val Glu Leu Glu Asn Tyr Gly Met Pro Phe
145 150 155 160
Ser Arg Thr Glu Asp Gly Lys Ile Tyr Gln Arg Ala Phe Gly Gly Gln
165 170 175
Ser Leu Lys Phe Gly Lys Gly Gly Gln Ala His Arg Cys Cys Cys Val
180 185 190
Ala Asp Arg Thr Gly His Ser Leu Leu His Thr Leu Tyr Gly Arg Ser
195 200 205
Leu Arg Tyr Asp Thr Ser Tyr Phe Val Glu Tyr Phe Ala Leu Asp Leu
210 215 220
Leu Met Glu Asn Gly Glu Cys Arg Gly Val Ile Ala Leu Cys Ile Glu
225 230 235 240
Asp Gly Ser Ile His Arg Ile Arg Ala Lys Asn Thr Val Val Ala Thr
245 250 255
Gly Gly Tyr Gly Arg Thr Tyr Phe Ser Cys Thr Ser Ala His Thr Ser
260 265 270
Thr Gly Asp Gly Thr Ala Met Ile Thr Arg Ala Gly Leu Pro Cys Gln
275 280 285
Asp Leu Glu Phe Val Gln Phe His Pro Thr Gly Ile Tyr Gly Ala Gly
290 295 300
Cys Leu Ile Thr Glu Gly Cys Arg Gly Glu Gly Gly Ile Leu Ile Asn
305 310 315 320
Ser Gln Gly Glu Arg Phe Met Glu Arg Tyr Ala Pro Val Ala Lys Asp
325 330 335
Leu Ala Ser Arg Asp Val Val Ser Arg Ser Met Thr Leu Glu Ile Arg
340 345 350
Glu Gly Arg Gly Cys Gly Pro Glu Lys Asp His Val Tyr Leu Gln Leu
355 360 365
His His Leu Pro Pro Glu Gln Leu Ala Thr Arg Leu Pro Gly Ile Ser
370 375 380
Glu Thr Ala Met Ile Phe Ala Gly Val Asp Val Thr Lys Glu Pro Ile
385 390 395 400
Pro Val Leu Pro Thr Val His Tyr Asn Met Gly Gly Ile Pro Thr Asn
405 410 415
Tyr Lys Gly Gln Val Leu Arg His Val Asn Gly Gln Asp Gln Ile Val
420 425 430
Pro Gly Leu Tyr Ala Cys Gly Glu Ala Ala Cys Ala Ser Val His Gly
435 440 445
Ala Asn Arg Leu Gly Ala Asn Ser Leu Leu Asp Leu Val Val Phe Gly
450 455 460
Arg Ala Cys Ala Leu Ser Ile Glu Glu Ser Cys Arg Pro Gly Asp Lys
465 470 475 480
Val Pro Pro Ile Lys Pro Asn Ala Gly Glu Glu Ser Val Met Asn Leu
485 490 495
Asp Lys Leu Arg Phe Ala Asp Gly Ser Ile Arg Thr Ser Glu Leu Arg
500 505 510
Leu Ser Met Gln Lys Ser Met Gln Asn His Ala Ala Val Phe Arg Val
515 520 525
Gly Ser Val Leu Gln Glu Gly Cys Gly Lys Ile Ser Lys Leu Tyr Gly
530 535 540
Asp Leu Lys His Leu Lys Thr Phe Asp Arg Gly Met Val Trp Asn Thr
545 550 555 560
Asp Leu Val Glu Thr Leu Glu Leu Gln Asn Leu Met Leu Cys Ala Leu
565 570 575
Gln Thr Ile Tyr Gly Ala Glu Ala Arg Lys Glu Ser Arg Gly Ala His
580 585 590
Ala Arg Glu Asp Tyr Lys Val Arg Ile Asp Glu Tyr Asp Tyr Ser Lys
595 600 605
Pro Ile Gln Gly Gln Gln Lys Lys Pro Phe Glu Glu His Trp Arg Lys
610 615 620
His Thr Leu Ser Tyr Val Asp Val Gly Thr Gly Lys Val Thr Leu Glu
625 630 635 640
Tyr Arg Pro Val Ile Asp Lys Thr Leu Asn Glu Ala Asp Cys Ala Thr
645 650 655
Val Pro Pro Ala Ile Arg Ser Tyr
660
<210> 150
<211> 472
<212> PRT
<213> 智人
<400> 150
Met Ala Thr Lys Cys Gly Asn Cys Gly Pro Gly Tyr Ser Thr Pro Leu
1 5 10 15
Glu Ala Met Lys Gly Pro Arg Glu Glu Ile Val Tyr Leu Pro Cys Ile
20 25 30
Tyr Arg Asn Thr Gly Thr Glu Ala Pro Asp Tyr Leu Ala Thr Val Asp
35 40 45
Val Asp Pro Lys Ser Pro Gln Tyr Cys Gln Val Ile His Arg Leu Pro
50 55 60
Met Pro Asn Leu Lys Asp Glu Leu His His Ser Gly Trp Asn Thr Cys
65 70 75 80
Ser Ser Cys Phe Gly Asp Ser Thr Lys Ser Arg Thr Lys Leu Val Leu
85 90 95
Pro Ser Leu Ile Ser Ser Arg Ile Tyr Val Val Asp Val Gly Ser Glu
100 105 110
Pro Arg Ala Pro Lys Leu His Lys Val Ile Glu Pro Lys Asp Ile His
115 120 125
Ala Lys Cys Glu Leu Ala Phe Leu His Thr Ser His Cys Leu Ala Ser
130 135 140
Gly Glu Val Met Ile Ser Ser Leu Gly Asp Val Lys Gly Asn Gly Lys
145 150 155 160
Gly Gly Phe Val Leu Leu Asp Gly Glu Thr Phe Glu Val Lys Gly Thr
165 170 175
Trp Glu Arg Pro Gly Gly Ala Ala Pro Leu Gly Tyr Asp Phe Trp Tyr
180 185 190
Gln Pro Arg His Asn Val Met Ile Ser Thr Glu Trp Ala Ala Pro Asn
195 200 205
Val Leu Arg Asp Gly Phe Asn Pro Ala Asp Val Glu Ala Gly Leu Tyr
210 215 220
Gly Ser His Leu Tyr Val Trp Asp Trp Gln Arg His Glu Ile Val Gln
225 230 235 240
Thr Leu Ser Leu Lys Asp Gly Leu Ile Pro Leu Glu Ile Arg Phe Leu
245 250 255
His Asn Pro Asp Ala Ala Gln Gly Phe Val Gly Cys Ala Leu Ser Ser
260 265 270
Thr Ile Gln Arg Phe Tyr Lys Asn Glu Gly Gly Thr Trp Ser Val Glu
275 280 285
Lys Val Ile Gln Val Pro Pro Lys Lys Val Lys Gly Trp Leu Leu Pro
290 295 300
Glu Met Pro Gly Leu Ile Thr Asp Ile Leu Leu Ser Leu Asp Asp Arg
305 310 315 320
Phe Leu Tyr Phe Ser Asn Trp Leu His Gly Asp Leu Arg Gln Tyr Asp
325 330 335
Ile Ser Asp Pro Gln Arg Pro Arg Leu Thr Gly Gln Leu Phe Leu Gly
340 345 350
Gly Ser Ile Val Lys Gly Gly Pro Val Gln Val Leu Glu Asp Glu Glu
355 360 365
Leu Lys Ser Gln Pro Glu Pro Leu Val Val Lys Gly Lys Arg Val Ala
370 375 380
Gly Gly Pro Gln Met Ile Gln Leu Ser Leu Asp Gly Lys Arg Leu Tyr
385 390 395 400
Ile Thr Thr Ser Leu Tyr Ser Ala Trp Asp Lys Gln Phe Tyr Pro Asp
405 410 415
Leu Ile Arg Glu Gly Ser Val Met Leu Gln Val Asp Val Asp Thr Val
420 425 430
Lys Gly Gly Leu Lys Leu Asn Pro Asn Phe Leu Val Asp Phe Gly Lys
435 440 445
Glu Pro Leu Gly Pro Ala Leu Ala His Glu Leu Arg Tyr Pro Gly Gly
450 455 460
Asp Cys Ser Ser Asp Ile Trp Ile
465 470
<210> 151
<211> 412
<212> PRT
<213> 智人
<400> 151
Met Pro Leu Gln Leu Leu Leu Leu Leu Ile Leu Leu Gly Pro Gly Asn
1 5 10 15
Ser Leu Gln Leu Trp Asp Thr Trp Ala Asp Glu Ala Glu Lys Ala Leu
20 25 30
Gly Pro Leu Leu Ala Arg Asp Arg Arg Gln Ala Thr Glu Tyr Glu Tyr
35 40 45
Leu Asp Tyr Asp Phe Leu Pro Glu Thr Glu Pro Pro Glu Met Leu Arg
50 55 60
Asn Ser Thr Asp Thr Thr Pro Leu Thr Gly Pro Gly Thr Pro Glu Ser
65 70 75 80
Thr Thr Val Glu Pro Ala Ala Arg Arg Ser Thr Gly Leu Asp Ala Gly
85 90 95
Gly Ala Val Thr Glu Leu Thr Thr Glu Leu Ala Asn Met Gly Asn Leu
100 105 110
Ser Thr Asp Ser Ala Ala Met Glu Ile Gln Thr Thr Gln Pro Ala Ala
115 120 125
Thr Glu Ala Gln Thr Thr Gln Pro Val Pro Thr Glu Ala Gln Thr Thr
130 135 140
Pro Leu Ala Ala Thr Glu Ala Gln Thr Thr Arg Leu Thr Ala Thr Glu
145 150 155 160
Ala Gln Thr Thr Pro Leu Ala Ala Thr Glu Ala Gln Thr Thr Pro Pro
165 170 175
Ala Ala Thr Glu Ala Gln Thr Thr Gln Pro Thr Gly Leu Glu Ala Gln
180 185 190
Thr Thr Ala Pro Ala Ala Met Glu Ala Gln Thr Thr Ala Pro Ala Ala
195 200 205
Met Glu Ala Gln Thr Thr Pro Pro Ala Ala Met Glu Ala Gln Thr Thr
210 215 220
Gln Thr Thr Ala Met Glu Ala Gln Thr Thr Ala Pro Glu Ala Thr Glu
225 230 235 240
Ala Gln Thr Thr Gln Pro Thr Ala Thr Glu Ala Gln Thr Thr Pro Leu
245 250 255
Ala Ala Met Glu Ala Leu Ser Thr Glu Pro Ser Ala Thr Glu Ala Leu
260 265 270
Ser Met Glu Pro Thr Thr Lys Arg Gly Leu Phe Ile Pro Phe Ser Val
275 280 285
Ser Ser Val Thr His Lys Gly Ile Pro Met Ala Ala Ser Asn Leu Ser
290 295 300
Val Asn Tyr Pro Val Gly Ala Pro Asp His Ile Ser Val Lys Gln Cys
305 310 315 320
Leu Leu Ala Ile Leu Ile Leu Ala Leu Val Ala Thr Ile Phe Phe Val
325 330 335
Cys Thr Val Val Leu Ala Val Arg Leu Ser Arg Lys Gly His Met Tyr
340 345 350
Pro Val Arg Asn Tyr Ser Pro Thr Glu Met Val Cys Ile Ser Ser Leu
355 360 365
Leu Pro Asp Gly Gly Glu Gly Pro Ser Ala Thr Ala Asn Gly Gly Leu
370 375 380
Ser Lys Ala Lys Ser Pro Gly Leu Thr Pro Glu Pro Arg Glu Asp Arg
385 390 395 400
Glu Gly Asp Asp Leu Thr Leu His Ser Phe Leu Pro
405 410
<210> 152
<211> 586
<212> PRT
<213> 智人
<400> 152
Met Lys Lys Ser Tyr Ser Gly Gly Thr Arg Thr Ser Ser Gly Arg Leu
1 5 10 15
Arg Arg Leu Gly Asp Ser Ser Gly Pro Ala Leu Lys Arg Ser Phe Glu
20 25 30
Val Glu Glu Val Glu Thr Pro Asn Ser Thr Pro Pro Arg Arg Val Gln
35 40 45
Thr Pro Leu Leu Arg Ala Thr Val Ala Ser Ser Thr Gln Lys Phe Gln
50 55 60
Asp Leu Gly Val Lys Asn Ser Glu Pro Ser Ala Arg His Val Asp Ser
65 70 75 80
Leu Ser Gln Arg Ser Pro Lys Ala Ser Leu Arg Arg Val Glu Leu Ser
85 90 95
Gly Pro Lys Ala Ala Glu Pro Val Ser Arg Arg Thr Glu Leu Ser Ile
100 105 110
Asp Ile Ser Ser Lys Gln Val Glu Asn Ala Gly Ala Ile Gly Pro Ser
115 120 125
Arg Phe Gly Leu Lys Arg Ala Glu Val Leu Gly His Lys Thr Pro Glu
130 135 140
Pro Ala Pro Arg Arg Thr Glu Ile Thr Ile Val Lys Pro Gln Glu Ser
145 150 155 160
Ala His Arg Arg Met Glu Pro Pro Ala Ser Lys Val Pro Glu Val Pro
165 170 175
Thr Ala Pro Ala Thr Asp Ala Ala Pro Lys Arg Val Glu Ile Gln Met
180 185 190
Pro Lys Pro Ala Glu Ala Pro Thr Ala Pro Ser Pro Ala Gln Thr Leu
195 200 205
Glu Asn Ser Glu Pro Ala Pro Val Ser Gln Leu Gln Ser Arg Leu Glu
210 215 220
Pro Lys Pro Gln Pro Pro Val Ala Glu Ala Thr Pro Arg Ser Gln Glu
225 230 235 240
Ala Thr Glu Ala Ala Pro Ser Cys Val Gly Asp Met Ala Asp Thr Pro
245 250 255
Arg Asp Ala Gly Leu Lys Gln Ala Pro Ala Ser Arg Asn Glu Lys Ala
260 265 270
Pro Val Asp Phe Gly Tyr Val Gly Ile Asp Ser Ile Leu Glu Gln Met
275 280 285
Arg Arg Lys Ala Met Lys Gln Gly Phe Glu Phe Asn Ile Met Val Val
290 295 300
Gly Gln Ser Gly Leu Gly Lys Ser Thr Leu Ile Asn Thr Leu Phe Lys
305 310 315 320
Ser Lys Ile Ser Arg Lys Ser Val Gln Pro Thr Ser Glu Glu Arg Ile
325 330 335
Pro Lys Thr Ile Glu Ile Lys Ser Ile Thr His Asp Ile Glu Glu Lys
340 345 350
Gly Val Arg Met Lys Leu Thr Val Ile Asp Thr Pro Gly Phe Gly Asp
355 360 365
His Ile Asn Asn Glu Asn Cys Trp Gln Pro Ile Met Lys Phe Ile Asn
370 375 380
Asp Gln Tyr Glu Lys Tyr Leu Gln Glu Glu Val Asn Ile Asn Arg Lys
385 390 395 400
Lys Arg Ile Pro Asp Thr Arg Val His Cys Cys Leu Tyr Phe Ile Pro
405 410 415
Ala Thr Gly His Ser Leu Arg Pro Leu Asp Ile Glu Phe Met Lys Arg
420 425 430
Leu Ser Lys Val Val Asn Ile Val Pro Val Ile Ala Lys Ala Asp Thr
435 440 445
Leu Thr Leu Glu Glu Arg Val His Phe Lys Gln Arg Ile Thr Ala Asp
450 455 460
Leu Leu Ser Asn Gly Ile Asp Val Tyr Pro Gln Lys Glu Phe Asp Glu
465 470 475 480
Asp Ser Glu Asp Arg Leu Val Asn Glu Lys Phe Arg Glu Met Ile Pro
485 490 495
Phe Ala Val Val Gly Ser Asp His Glu Tyr Gln Val Asn Gly Lys Arg
500 505 510
Ile Leu Gly Arg Lys Thr Lys Trp Gly Thr Ile Glu Val Glu Asn Thr
515 520 525
Thr His Cys Glu Phe Ala Tyr Leu Arg Asp Leu Leu Ile Arg Thr His
530 535 540
Met Gln Asn Ile Lys Asp Ile Thr Ser Ser Ile His Phe Glu Ala Tyr
545 550 555 560
Arg Val Lys Arg Leu Asn Glu Gly Ser Ser Ala Met Ala Asn Gly Met
565 570 575
Glu Glu Lys Glu Pro Glu Ala Pro Glu Met
580 585
<210> 153
<211> 418
<212> PRT
<213> 智人
<400> 153
Met Pro Ser Ser Val Ser Trp Gly Ile Leu Leu Leu Ala Gly Leu Cys
1 5 10 15
Cys Leu Val Pro Val Ser Leu Ala Glu Asp Pro Gln Gly Asp Ala Ala
20 25 30
Gln Lys Thr Asp Thr Ser His His Asp Gln Asp His Pro Thr Phe Asn
35 40 45
Lys Ile Thr Pro Asn Leu Ala Glu Phe Ala Phe Ser Leu Tyr Arg Gln
50 55 60
Leu Ala His Gln Ser Asn Ser Thr Asn Ile Phe Phe Ser Pro Val Ser
65 70 75 80
Ile Ala Thr Ala Phe Ala Met Leu Ser Leu Gly Thr Lys Ala Asp Thr
85 90 95
His Asp Glu Ile Leu Glu Gly Leu Asn Phe Asn Leu Thr Glu Ile Pro
100 105 110
Glu Ala Gln Ile His Glu Gly Phe Gln Glu Leu Leu Arg Thr Leu Asn
115 120 125
Gln Pro Asp Ser Gln Leu Gln Leu Thr Thr Gly Asn Gly Leu Phe Leu
130 135 140
Ser Glu Gly Leu Lys Leu Val Asp Lys Phe Leu Glu Asp Val Lys Lys
145 150 155 160
Leu Tyr His Ser Glu Ala Phe Thr Val Asn Phe Gly Asp Thr Glu Glu
165 170 175
Ala Lys Lys Gln Ile Asn Asp Tyr Val Glu Lys Gly Thr Gln Gly Lys
180 185 190
Ile Val Asp Leu Val Lys Glu Leu Asp Arg Asp Thr Val Phe Ala Leu
195 200 205
Val Asn Tyr Ile Phe Phe Lys Gly Lys Trp Glu Arg Pro Phe Glu Val
210 215 220
Lys Asp Thr Glu Glu Glu Asp Phe His Val Asp Gln Val Thr Thr Val
225 230 235 240
Lys Val Pro Met Met Lys Arg Leu Gly Met Phe Asn Ile Gln His Cys
245 250 255
Lys Lys Leu Ser Ser Trp Val Leu Leu Met Lys Tyr Leu Gly Asn Ala
260 265 270
Thr Ala Ile Phe Phe Leu Pro Asp Glu Gly Lys Leu Gln His Leu Glu
275 280 285
Asn Glu Leu Thr His Asp Ile Ile Thr Lys Phe Leu Glu Asn Glu Asp
290 295 300
Arg Arg Ser Ala Ser Leu His Leu Pro Lys Leu Ser Ile Thr Gly Thr
305 310 315 320
Tyr Asp Leu Lys Ser Val Leu Gly Gln Leu Gly Ile Thr Lys Val Phe
325 330 335
Ser Asn Gly Ala Asp Leu Ser Gly Val Thr Glu Glu Ala Pro Leu Lys
340 345 350
Leu Ser Lys Ala Val His Lys Ala Val Leu Thr Ile Asp Glu Lys Gly
355 360 365
Thr Glu Ala Ala Gly Ala Met Phe Leu Glu Ala Ile Pro Met Ser Ile
370 375 380
Pro Pro Glu Val Lys Phe Asn Lys Pro Phe Val Phe Leu Met Ile Glu
385 390 395 400
Gln Asn Thr Lys Ser Pro Leu Phe Met Gly Lys Val Val Asn Pro Thr
405 410 415
Gln Lys
<210> 154
<211> 423
<212> PRT
<213> 智人
<400> 154
Met Glu Arg Met Leu Pro Leu Leu Ala Leu Gly Leu Leu Ala Ala Gly
1 5 10 15
Phe Cys Pro Ala Val Leu Cys His Pro Asn Ser Pro Leu Asp Glu Glu
20 25 30
Asn Leu Thr Gln Glu Asn Gln Asp Arg Gly Thr His Val Asp Leu Gly
35 40 45
Leu Ala Ser Ala Asn Val Asp Phe Ala Phe Ser Leu Tyr Lys Gln Leu
50 55 60
Val Leu Lys Ala Pro Asp Lys Asn Val Ile Phe Ser Pro Leu Ser Ile
65 70 75 80
Ser Thr Ala Leu Ala Phe Leu Ser Leu Gly Ala His Asn Thr Thr Leu
85 90 95
Thr Glu Ile Leu Lys Gly Leu Lys Phe Asn Leu Thr Glu Thr Ser Glu
100 105 110
Ala Glu Ile His Gln Ser Phe Gln His Leu Leu Arg Thr Leu Asn Gln
115 120 125
Ser Ser Asp Glu Leu Gln Leu Ser Met Gly Asn Ala Met Phe Val Lys
130 135 140
Glu Gln Leu Ser Leu Leu Asp Arg Phe Thr Glu Asp Ala Lys Arg Leu
145 150 155 160
Tyr Gly Ser Glu Ala Phe Ala Thr Asp Phe Gln Asp Ser Ala Ala Ala
165 170 175
Lys Lys Leu Ile Asn Asp Tyr Val Lys Asn Gly Thr Arg Gly Lys Ile
180 185 190
Thr Asp Leu Ile Lys Asp Leu Asp Ser Gln Thr Met Met Val Leu Val
195 200 205
Asn Tyr Ile Phe Phe Lys Ala Lys Trp Glu Met Pro Phe Asp Pro Gln
210 215 220
Asp Thr His Gln Ser Arg Phe Tyr Leu Ser Lys Lys Lys Trp Val Met
225 230 235 240
Val Pro Met Met Ser Leu His His Leu Thr Ile Pro Tyr Phe Arg Asp
245 250 255
Glu Glu Leu Ser Cys Thr Val Val Glu Leu Lys Tyr Thr Gly Asn Ala
260 265 270
Ser Ala Leu Phe Ile Leu Pro Asp Gln Asp Lys Met Glu Glu Val Glu
275 280 285
Ala Met Leu Leu Pro Glu Thr Leu Lys Arg Trp Arg Asp Ser Leu Glu
290 295 300
Phe Arg Glu Ile Gly Glu Leu Tyr Leu Pro Lys Phe Ser Ile Ser Arg
305 310 315 320
Asp Tyr Asn Leu Asn Asp Ile Leu Leu Gln Leu Gly Ile Glu Glu Ala
325 330 335
Phe Thr Ser Lys Ala Asp Leu Ser Gly Ile Thr Gly Ala Arg Asn Leu
340 345 350
Ala Val Ser Gln Val Val His Lys Ala Val Leu Asp Val Phe Glu Glu
355 360 365
Gly Thr Glu Ala Ser Ala Ala Thr Ala Val Lys Ile Thr Leu Leu Ser
370 375 380
Ala Leu Val Glu Thr Arg Thr Ile Val Arg Phe Asn Arg Pro Phe Leu
385 390 395 400
Met Ile Ile Val Pro Thr Asp Thr Gln Asn Ile Phe Phe Met Ser Lys
405 410 415
Val Thr Asn Pro Lys Gln Ala
420
<210> 155
<211> 379
<212> PRT
<213> 智人
<400> 155
Met Glu Gln Leu Ser Ser Ala Asn Thr Arg Phe Ala Leu Asp Leu Phe
1 5 10 15
Leu Ala Leu Ser Glu Asn Asn Pro Ala Gly Asn Ile Phe Ile Ser Pro
20 25 30
Phe Ser Ile Ser Ser Ala Met Ala Met Val Phe Leu Gly Thr Arg Gly
35 40 45
Asn Thr Ala Ala Gln Leu Ser Lys Thr Phe His Phe Asn Thr Val Glu
50 55 60
Glu Val His Ser Arg Phe Gln Ser Leu Asn Ala Asp Ile Asn Lys Arg
65 70 75 80
Gly Ala Ser Tyr Ile Leu Lys Leu Ala Asn Arg Leu Tyr Gly Glu Lys
85 90 95
Thr Tyr Asn Phe Leu Pro Glu Phe Leu Val Ser Thr Gln Lys Thr Tyr
100 105 110
Gly Ala Asp Leu Ala Ser Val Asp Phe Gln His Ala Ser Glu Asp Ala
115 120 125
Arg Lys Thr Ile Asn Gln Trp Val Lys Gly Gln Thr Glu Gly Lys Ile
130 135 140
Pro Glu Leu Leu Ala Ser Gly Met Val Asp Asn Met Thr Lys Leu Val
145 150 155 160
Leu Val Asn Ala Ile Tyr Phe Lys Gly Asn Trp Lys Asp Lys Phe Met
165 170 175
Lys Glu Ala Thr Thr Asn Ala Pro Phe Arg Leu Asn Lys Lys Asp Arg
180 185 190
Lys Thr Val Lys Met Met Tyr Gln Lys Lys Lys Phe Ala Tyr Gly Tyr
195 200 205
Ile Glu Asp Leu Lys Cys Arg Val Leu Glu Leu Pro Tyr Gln Gly Glu
210 215 220
Glu Leu Ser Met Val Ile Leu Leu Pro Asp Asp Ile Glu Asp Glu Ser
225 230 235 240
Thr Gly Leu Lys Lys Ile Glu Glu Gln Leu Thr Leu Glu Lys Leu His
245 250 255
Glu Trp Thr Lys Pro Glu Asn Leu Asp Phe Ile Glu Val Asn Val Ser
260 265 270
Leu Pro Arg Phe Lys Leu Glu Glu Ser Tyr Thr Leu Asn Ser Asp Leu
275 280 285
Ala Arg Leu Gly Val Gln Asp Leu Phe Asn Ser Ser Lys Ala Asp Leu
290 295 300
Ser Gly Met Ser Gly Ala Arg Asp Ile Phe Ile Ser Lys Ile Val His
305 310 315 320
Lys Ser Phe Val Glu Val Asn Glu Glu Gly Thr Glu Ala Ala Ala Ala
325 330 335
Thr Ala Gly Ile Ala Thr Phe Cys Met Leu Met Pro Glu Glu Asn Phe
340 345 350
Thr Ala Asp His Pro Phe Leu Phe Phe Ile Arg His Asn Ser Ser Gly
355 360 365
Ser Ile Leu Phe Leu Gly Arg Phe Ser Ser Pro
370 375
<210> 156
<211> 376
<212> PRT
<213> 智人
<400> 156
Met Asp Val Leu Ala Glu Ala Asn Gly Thr Phe Ala Leu Asn Leu Leu
1 5 10 15
Lys Thr Leu Gly Lys Asp Asn Ser Lys Asn Val Phe Phe Ser Pro Met
20 25 30
Ser Met Ser Cys Ala Leu Ala Met Val Tyr Met Gly Ala Lys Gly Asn
35 40 45
Thr Ala Ala Gln Met Ala Gln Ile Leu Ser Phe Asn Lys Ser Gly Gly
50 55 60
Gly Gly Asp Ile His Gln Gly Phe Gln Ser Leu Leu Thr Glu Val Asn
65 70 75 80
Lys Thr Gly Thr Gln Tyr Leu Leu Arg Met Ala Asn Arg Leu Phe Gly
85 90 95
Glu Lys Ser Cys Asp Phe Leu Ser Ser Phe Arg Asp Ser Cys Gln Lys
100 105 110
Phe Tyr Gln Ala Glu Met Glu Glu Leu Asp Phe Ile Ser Ala Val Glu
115 120 125
Lys Ser Arg Lys His Ile Asn Thr Trp Val Ala Glu Lys Thr Glu Gly
130 135 140
Lys Ile Ala Glu Leu Leu Ser Pro Gly Ser Val Asp Pro Leu Thr Arg
145 150 155 160
Leu Val Leu Val Asn Ala Val Tyr Phe Arg Gly Asn Trp Asp Glu Gln
165 170 175
Phe Asp Lys Glu Asn Thr Glu Glu Arg Leu Phe Lys Val Ser Lys Asn
180 185 190
Glu Glu Lys Pro Val Gln Met Met Phe Lys Gln Ser Thr Phe Lys Lys
195 200 205
Thr Tyr Ile Gly Glu Ile Phe Thr Gln Ile Leu Val Leu Pro Tyr Val
210 215 220
Gly Lys Glu Leu Asn Met Ile Ile Met Leu Pro Asp Glu Thr Thr Asp
225 230 235 240
Leu Arg Thr Val Glu Lys Glu Leu Thr Tyr Glu Lys Phe Val Glu Trp
245 250 255
Thr Arg Leu Asp Met Met Asp Glu Glu Glu Val Glu Val Ser Leu Pro
260 265 270
Arg Phe Lys Leu Glu Glu Ser Tyr Asp Met Glu Ser Val Leu Arg Asn
275 280 285
Leu Gly Met Thr Asp Ala Phe Glu Leu Gly Lys Ala Asp Phe Ser Gly
290 295 300
Met Ser Gln Thr Asp Leu Ser Leu Ser Lys Val Val His Lys Ser Phe
305 310 315 320
Val Glu Val Asn Glu Glu Gly Thr Glu Ala Ala Ala Ala Thr Ala Ala
325 330 335
Ile Met Met Met Arg Cys Ala Arg Phe Val Pro Arg Phe Cys Ala Asp
340 345 350
His Pro Phe Leu Phe Phe Ile Gln His Ser Lys Thr Asn Gly Ile Leu
355 360 365
Phe Cys Gly Arg Phe Ser Ser Pro
370 375
<210> 157
<211> 1217
<212> PRT
<213> 智人
<400> 157
Met Phe Leu Tyr Asn Leu Thr Leu Gln Arg Ala Thr Gly Ile Ser Phe
1 5 10 15
Ala Ile His Gly Asn Phe Ser Gly Thr Lys Gln Gln Glu Ile Val Val
20 25 30
Ser Arg Gly Lys Ile Leu Glu Leu Leu Arg Pro Asp Pro Asn Thr Gly
35 40 45
Lys Val His Thr Leu Leu Thr Val Glu Val Phe Gly Val Ile Arg Ser
50 55 60
Leu Met Ala Phe Arg Leu Thr Gly Gly Thr Lys Asp Tyr Ile Val Val
65 70 75 80
Gly Ser Asp Ser Gly Arg Ile Val Ile Leu Glu Tyr Gln Pro Ser Lys
85 90 95
Asn Met Phe Glu Lys Ile His Gln Glu Thr Phe Gly Lys Ser Gly Cys
100 105 110
Arg Arg Ile Val Pro Gly Gln Phe Leu Ala Val Asp Pro Lys Gly Arg
115 120 125
Ala Val Met Ile Ser Ala Ile Glu Lys Gln Lys Leu Val Tyr Ile Leu
130 135 140
Asn Arg Asp Ala Ala Ala Arg Leu Thr Ile Ser Ser Pro Leu Glu Ala
145 150 155 160
His Lys Ala Asn Thr Leu Val Tyr His Val Val Gly Val Asp Val Gly
165 170 175
Phe Glu Asn Pro Met Phe Ala Cys Leu Glu Met Asp Tyr Glu Glu Ala
180 185 190
Asp Asn Asp Pro Thr Gly Glu Ala Ala Ala Asn Thr Gln Gln Thr Leu
195 200 205
Thr Phe Tyr Glu Leu Asp Leu Gly Leu Asn His Val Val Arg Lys Tyr
210 215 220
Ser Glu Pro Leu Glu Glu His Gly Asn Phe Leu Ile Thr Val Pro Gly
225 230 235 240
Gly Ser Asp Gly Pro Ser Gly Val Leu Ile Cys Ser Glu Asn Tyr Ile
245 250 255
Thr Tyr Lys Asn Phe Gly Asp Gln Pro Asp Ile Arg Cys Pro Ile Pro
260 265 270
Arg Arg Arg Asn Asp Leu Asp Asp Pro Glu Arg Gly Met Ile Phe Val
275 280 285
Cys Ser Ala Thr His Lys Thr Lys Ser Met Phe Phe Phe Leu Ala Gln
290 295 300
Thr Glu Gln Gly Asp Ile Phe Lys Ile Thr Leu Glu Thr Asp Glu Asp
305 310 315 320
Met Val Thr Glu Ile Arg Leu Lys Tyr Phe Asp Thr Val Pro Val Ala
325 330 335
Ala Ala Met Cys Val Leu Lys Thr Gly Phe Leu Phe Val Ala Ser Glu
340 345 350
Phe Gly Asn His Tyr Leu Tyr Gln Ile Ala His Leu Gly Asp Asp Asp
355 360 365
Glu Glu Pro Glu Phe Ser Ser Ala Met Pro Leu Glu Glu Gly Asp Thr
370 375 380
Phe Phe Phe Gln Pro Arg Pro Leu Lys Asn Leu Val Leu Val Asp Glu
385 390 395 400
Leu Asp Ser Leu Ser Pro Ile Leu Phe Cys Gln Ile Ala Asp Leu Ala
405 410 415
Asn Glu Asp Thr Pro Gln Leu Tyr Val Ala Cys Gly Arg Gly Pro Arg
420 425 430
Ser Ser Leu Arg Val Leu Arg His Gly Leu Glu Val Ser Glu Met Ala
435 440 445
Val Ser Glu Leu Pro Gly Asn Pro Asn Ala Val Trp Thr Val Arg Arg
450 455 460
His Ile Glu Asp Glu Phe Asp Ala Tyr Ile Ile Val Ser Phe Val Asn
465 470 475 480
Ala Thr Leu Val Leu Ser Ile Gly Glu Thr Val Glu Glu Val Thr Asp
485 490 495
Ser Gly Phe Leu Gly Thr Thr Pro Thr Leu Ser Cys Ser Leu Leu Gly
500 505 510
Asp Asp Ala Leu Val Gln Val Tyr Pro Asp Gly Ile Arg His Ile Arg
515 520 525
Ala Asp Lys Arg Val Asn Glu Trp Lys Thr Pro Gly Lys Lys Thr Ile
530 535 540
Val Lys Cys Ala Val Asn Gln Arg Gln Val Val Ile Ala Leu Thr Gly
545 550 555 560
Gly Glu Leu Val Tyr Phe Glu Met Asp Pro Ser Gly Gln Leu Asn Glu
565 570 575
Tyr Thr Glu Arg Lys Glu Met Ser Ala Asp Val Val Cys Met Ser Leu
580 585 590
Ala Asn Val Pro Pro Gly Glu Gln Arg Ser Arg Phe Leu Ala Val Gly
595 600 605
Leu Val Asp Asn Thr Val Arg Ile Ile Ser Leu Asp Pro Ser Asp Cys
610 615 620
Leu Gln Pro Leu Ser Met Gln Ala Leu Pro Ala Gln Pro Glu Ser Leu
625 630 635 640
Cys Ile Val Glu Met Gly Gly Thr Glu Lys Gln Asp Glu Leu Gly Glu
645 650 655
Arg Gly Ser Ile Gly Phe Leu Tyr Leu Asn Ile Gly Leu Gln Asn Gly
660 665 670
Val Leu Leu Arg Thr Val Leu Asp Pro Val Thr Gly Asp Leu Ser Asp
675 680 685
Thr Arg Thr Arg Tyr Leu Gly Ser Arg Pro Val Lys Leu Phe Arg Val
690 695 700
Arg Met Gln Gly Gln Glu Ala Val Leu Ala Met Ser Ser Arg Ser Trp
705 710 715 720
Leu Ser Tyr Ser Tyr Gln Ser Arg Phe His Leu Thr Pro Leu Ser Tyr
725 730 735
Glu Thr Leu Glu Phe Ala Ser Gly Phe Ala Ser Glu Gln Cys Pro Glu
740 745 750
Gly Ile Val Ala Ile Ser Thr Asn Thr Leu Arg Ile Leu Ala Leu Glu
755 760 765
Lys Leu Gly Ala Val Phe Asn Gln Val Ala Phe Pro Leu Gln Tyr Thr
770 775 780
Pro Arg Lys Phe Val Ile His Pro Glu Ser Asn Asn Leu Ile Ile Ile
785 790 795 800
Glu Thr Asp His Asn Ala Tyr Thr Glu Ala Thr Lys Ala Gln Arg Lys
805 810 815
Gln Gln Met Ala Glu Glu Met Val Glu Ala Ala Gly Glu Asp Glu Arg
820 825 830
Glu Leu Ala Ala Glu Met Ala Ala Ala Phe Leu Asn Glu Asn Leu Pro
835 840 845
Glu Ser Ile Phe Gly Ala Pro Lys Ala Gly Asn Gly Gln Trp Ala Ser
850 855 860
Val Ile Arg Val Met Asn Pro Ile Gln Gly Asn Thr Leu Asp Leu Val
865 870 875 880
Gln Leu Glu Gln Asn Glu Ala Ala Phe Ser Val Ala Val Cys Arg Phe
885 890 895
Ser Asn Thr Gly Glu Asp Trp Tyr Val Leu Val Gly Val Ala Lys Asp
900 905 910
Leu Ile Leu Asn Pro Arg Ser Val Ala Gly Gly Phe Val Tyr Thr Tyr
915 920 925
Lys Leu Val Asn Asn Gly Glu Lys Leu Glu Phe Leu His Lys Thr Pro
930 935 940
Val Glu Glu Val Pro Ala Ala Ile Ala Pro Phe Gln Gly Arg Val Leu
945 950 955 960
Ile Gly Val Gly Lys Leu Leu Arg Val Tyr Asp Leu Gly Lys Lys Lys
965 970 975
Leu Leu Arg Lys Cys Glu Asn Lys His Ile Ala Asn Tyr Ile Ser Gly
980 985 990
Ile Gln Thr Ile Gly His Arg Val Ile Val Ser Asp Val Gln Glu Ser
995 1000 1005
Phe Ile Trp Val Arg Tyr Lys Arg Asn Glu Asn Gln Leu Ile Ile
1010 1015 1020
Phe Ala Asp Asp Thr Tyr Pro Arg Trp Val Thr Thr Ala Ser Leu
1025 1030 1035
Leu Asp Tyr Asp Thr Val Ala Gly Ala Asp Lys Phe Gly Asn Ile
1040 1045 1050
Cys Val Val Arg Leu Pro Pro Asn Thr Asn Asp Glu Val Asp Glu
1055 1060 1065
Asp Pro Thr Gly Asn Lys Ala Leu Trp Asp Arg Gly Leu Leu Asn
1070 1075 1080
Gly Ala Ser Gln Lys Ala Glu Val Ile Met Asn Tyr His Val Gly
1085 1090 1095
Glu Thr Val Leu Ser Leu Gln Lys Thr Thr Leu Ile Pro Gly Gly
1100 1105 1110
Ser Glu Ser Leu Val Tyr Thr Thr Leu Ser Gly Gly Ile Gly Ile
1115 1120 1125
Leu Val Pro Phe Thr Ser His Glu Asp His Asp Phe Phe Gln His
1130 1135 1140
Val Glu Met His Leu Arg Ser Glu His Pro Pro Leu Cys Gly Arg
1145 1150 1155
Asp His Leu Ser Phe Arg Ser Tyr Tyr Phe Pro Val Lys Asn Val
1160 1165 1170
Ile Asp Gly Asp Leu Cys Glu Gln Phe Asn Ser Met Glu Pro Asn
1175 1180 1185
Lys Gln Lys Asn Val Ser Glu Glu Leu Asp Arg Thr Pro Pro Glu
1190 1195 1200
Val Ser Lys Lys Leu Glu Asp Ile Arg Thr Arg Tyr Ala Phe
1205 1210 1215
<210> 158
<211> 163
<212> PRT
<213> 智人
<400> 158
Met Pro Ser Ile Lys Leu Gln Ser Ser Asp Gly Glu Ile Phe Glu Val
1 5 10 15
Asp Val Glu Ile Ala Lys Gln Ser Val Thr Ile Lys Thr Met Leu Glu
20 25 30
Asp Leu Gly Met Asp Asp Glu Gly Asp Asp Asp Pro Val Pro Leu Pro
35 40 45
Asn Val Asn Ala Ala Ile Leu Lys Lys Val Ile Gln Trp Cys Thr His
50 55 60
His Lys Asp Asp Pro Pro Pro Pro Glu Asp Asp Glu Asn Lys Glu Lys
65 70 75 80
Arg Thr Asp Asp Ile Pro Val Trp Asp Gln Glu Phe Leu Lys Val Asp
85 90 95
Gln Gly Thr Leu Phe Glu Leu Ile Leu Ala Ala Asn Tyr Leu Asp Ile
100 105 110
Lys Gly Leu Leu Asp Val Thr Cys Lys Thr Val Ala Asn Met Ile Lys
115 120 125
Gly Lys Thr Pro Glu Glu Ile Arg Lys Thr Phe Asn Ile Lys Asn Asp
130 135 140
Phe Thr Glu Glu Glu Glu Ala Gln Val Arg Lys Glu Asn Gln Trp Cys
145 150 155 160
Glu Glu Lys
<210> 159
<211> 298
<212> PRT
<213> 智人
<400> 159
Met Thr Asp Ala Ala Val Ser Phe Ala Lys Asp Phe Leu Ala Gly Gly
1 5 10 15
Val Ala Ala Ala Ile Ser Lys Thr Ala Val Ala Pro Ile Glu Arg Val
20 25 30
Lys Leu Leu Leu Gln Val Gln His Ala Ser Lys Gln Ile Thr Ala Asp
35 40 45
Lys Gln Tyr Lys Gly Ile Ile Asp Cys Val Val Arg Ile Pro Lys Glu
50 55 60
Gln Gly Val Leu Ser Phe Trp Arg Gly Asn Leu Ala Asn Val Ile Arg
65 70 75 80
Tyr Phe Pro Thr Gln Ala Leu Asn Phe Ala Phe Lys Asp Lys Tyr Lys
85 90 95
Gln Ile Phe Leu Gly Gly Val Asp Lys Arg Thr Gln Phe Trp Leu Tyr
100 105 110
Phe Ala Gly Asn Leu Ala Ser Gly Gly Ala Ala Gly Ala Thr Ser Leu
115 120 125
Cys Phe Val Tyr Pro Leu Asp Phe Ala Arg Thr Arg Leu Ala Ala Asp
130 135 140
Val Gly Lys Ala Gly Ala Glu Arg Glu Phe Arg Gly Leu Gly Asp Cys
145 150 155 160
Leu Val Lys Ile Tyr Lys Ser Asp Gly Ile Lys Gly Leu Tyr Gln Gly
165 170 175
Phe Asn Val Ser Val Gln Gly Ile Ile Ile Tyr Arg Ala Ala Tyr Phe
180 185 190
Gly Ile Tyr Asp Thr Ala Lys Gly Met Leu Pro Asp Pro Lys Asn Thr
195 200 205
His Ile Val Ile Ser Trp Met Ile Ala Gln Thr Val Thr Ala Val Ala
210 215 220
Gly Leu Thr Ser Tyr Pro Phe Asp Thr Val Arg Arg Arg Met Met Met
225 230 235 240
Gln Ser Gly Arg Lys Gly Thr Asp Ile Met Tyr Thr Gly Thr Leu Asp
245 250 255
Cys Trp Arg Lys Ile Ala Arg Asp Glu Gly Gly Lys Ala Phe Phe Lys
260 265 270
Gly Ala Trp Ser Asn Val Leu Arg Gly Met Gly Gly Ala Phe Val Leu
275 280 285
Val Leu Tyr Asp Glu Ile Lys Lys Tyr Thr
290 295
<210> 160
<211> 79
<212> PRT
<213> 智人
<400> 160
Met Lys Val Thr Gly Ile Phe Leu Leu Ser Ala Leu Ala Leu Leu Ser
1 5 10 15
Leu Ser Gly Asn Thr Gly Ala Asp Ser Leu Gly Arg Glu Ala Lys Cys
20 25 30
Tyr Asn Glu Leu Asn Gly Cys Thr Lys Ile Tyr Asp Pro Val Cys Gly
35 40 45
Thr Asp Gly Asn Thr Tyr Pro Asn Glu Cys Val Leu Cys Phe Glu Asn
50 55 60
Arg Lys Arg Gln Thr Ser Ile Leu Ile Gln Lys Ser Gly Pro Cys
65 70 75
<210> 161
<211> 331
<212> PRT
<213> 智人
<400> 161
Met Glu Asn Pro Ser Pro Ala Ala Ala Leu Gly Lys Ala Leu Cys Ala
1 5 10 15
Leu Leu Leu Ala Thr Leu Gly Ala Ala Gly Gln Pro Leu Gly Gly Glu
20 25 30
Ser Ile Cys Ser Ala Arg Ala Leu Ala Lys Tyr Ser Ile Thr Phe Thr
35 40 45
Gly Lys Trp Ser Gln Thr Ala Phe Pro Lys Gln Tyr Pro Leu Phe Arg
50 55 60
Pro Pro Ala Gln Trp Ser Ser Leu Leu Gly Ala Ala His Ser Ser Asp
65 70 75 80
Tyr Ser Met Trp Arg Lys Asn Gln Tyr Val Ser Asn Gly Leu Arg Asp
85 90 95
Phe Ala Glu Arg Gly Glu Ala Trp Ala Leu Met Lys Glu Ile Glu Ala
100 105 110
Ala Gly Glu Ala Leu Gln Ser Val His Glu Val Phe Ser Ala Pro Ala
115 120 125
Val Pro Ser Gly Thr Gly Gln Thr Ser Ala Glu Leu Glu Val Gln Arg
130 135 140
Arg His Ser Leu Val Ser Phe Val Val Arg Ile Val Pro Ser Pro Asp
145 150 155 160
Trp Phe Val Gly Val Asp Ser Leu Asp Leu Cys Asp Gly Asp Arg Trp
165 170 175
Arg Glu Gln Ala Ala Leu Asp Leu Tyr Pro Tyr Asp Ala Gly Thr Asp
180 185 190
Ser Gly Phe Thr Phe Ser Ser Pro Asn Phe Ala Thr Ile Pro Gln Asp
195 200 205
Thr Val Thr Glu Ile Thr Ser Ser Ser Pro Ser His Pro Ala Asn Ser
210 215 220
Phe Tyr Tyr Pro Arg Leu Lys Ala Leu Pro Pro Ile Ala Arg Val Thr
225 230 235 240
Leu Val Arg Leu Arg Gln Ser Pro Arg Ala Phe Ile Pro Pro Ala Pro
245 250 255
Val Leu Pro Ser Arg Asp Asn Glu Ile Val Asp Ser Ala Ser Val Pro
260 265 270
Glu Thr Pro Leu Asp Cys Glu Val Ser Leu Trp Ser Ser Trp Gly Leu
275 280 285
Cys Gly Gly His Cys Gly Arg Leu Gly Thr Lys Ser Arg Thr Arg Tyr
290 295 300
Val Arg Val Gln Pro Ala Asn Asn Gly Ser Pro Cys Pro Glu Leu Glu
305 310 315 320
Glu Glu Ala Glu Cys Val Pro Asp Asn Cys Val
325 330
<210> 162
<211> 314
<212> PRT
<213> 智人
<400> 162
Met Arg Ile Ala Val Ile Cys Phe Cys Leu Leu Gly Ile Thr Cys Ala
1 5 10 15
Ile Pro Val Lys Gln Ala Asp Ser Gly Ser Ser Glu Glu Lys Gln Leu
20 25 30
Tyr Asn Lys Tyr Pro Asp Ala Val Ala Thr Trp Leu Asn Pro Asp Pro
35 40 45
Ser Gln Lys Gln Asn Leu Leu Ala Pro Gln Asn Ala Val Ser Ser Glu
50 55 60
Glu Thr Asn Asp Phe Lys Gln Glu Thr Leu Pro Ser Lys Ser Asn Glu
65 70 75 80
Ser His Asp His Met Asp Asp Met Asp Asp Glu Asp Asp Asp Asp His
85 90 95
Val Asp Ser Gln Asp Ser Ile Asp Ser Asn Asp Ser Asp Asp Val Asp
100 105 110
Asp Thr Asp Asp Ser His Gln Ser Asp Glu Ser His His Ser Asp Glu
115 120 125
Ser Asp Glu Leu Val Thr Asp Phe Pro Thr Asp Leu Pro Ala Thr Glu
130 135 140
Val Phe Thr Pro Val Val Pro Thr Val Asp Thr Tyr Asp Gly Arg Gly
145 150 155 160
Asp Ser Val Val Tyr Gly Leu Arg Ser Lys Ser Lys Lys Phe Arg Arg
165 170 175
Pro Asp Ile Gln Tyr Pro Asp Ala Thr Asp Glu Asp Ile Thr Ser His
180 185 190
Met Glu Ser Glu Glu Leu Asn Gly Ala Tyr Lys Ala Ile Pro Val Ala
195 200 205
Gln Asp Leu Asn Ala Pro Ser Asp Trp Asp Ser Arg Gly Lys Asp Ser
210 215 220
Tyr Glu Thr Ser Gln Leu Asp Asp Gln Ser Ala Glu Thr His Ser His
225 230 235 240
Lys Gln Ser Arg Leu Tyr Lys Arg Lys Ala Asn Asp Glu Ser Asn Glu
245 250 255
His Ser Asp Val Ile Asp Ser Gln Glu Leu Ser Lys Val Ser Arg Glu
260 265 270
Phe His Ser His Glu Phe His Ser His Glu Asp Met Leu Val Val Asp
275 280 285
Pro Lys Ser Lys Glu Glu Asp Lys His Leu Lys Phe Arg Ile Ser His
290 295 300
Glu Leu Asp Ser Ala Ser Ser Glu Val Asn
305 310
<210> 163
<211> 536
<212> PRT
<213> 智人
<400> 163
Met Gly Ser Asn Lys Ser Lys Pro Lys Asp Ala Ser Gln Arg Arg Arg
1 5 10 15
Ser Leu Glu Pro Ala Glu Asn Val His Gly Ala Gly Gly Gly Ala Phe
20 25 30
Pro Ala Ser Gln Thr Pro Ser Lys Pro Ala Ser Ala Asp Gly His Arg
35 40 45
Gly Pro Ser Ala Ala Phe Ala Pro Ala Ala Ala Glu Pro Lys Leu Phe
50 55 60
Gly Gly Phe Asn Ser Ser Asp Thr Val Thr Ser Pro Gln Arg Ala Gly
65 70 75 80
Pro Leu Ala Gly Gly Val Thr Thr Phe Val Ala Leu Tyr Asp Tyr Glu
85 90 95
Ser Arg Thr Glu Thr Asp Leu Ser Phe Lys Lys Gly Glu Arg Leu Gln
100 105 110
Ile Val Asn Asn Thr Glu Gly Asp Trp Trp Leu Ala His Ser Leu Ser
115 120 125
Thr Gly Gln Thr Gly Tyr Ile Pro Ser Asn Tyr Val Ala Pro Ser Asp
130 135 140
Ser Ile Gln Ala Glu Glu Trp Tyr Phe Gly Lys Ile Thr Arg Arg Glu
145 150 155 160
Ser Glu Arg Leu Leu Leu Asn Ala Glu Asn Pro Arg Gly Thr Phe Leu
165 170 175
Val Arg Glu Ser Glu Thr Thr Lys Gly Ala Tyr Cys Leu Ser Val Ser
180 185 190
Asp Phe Asp Asn Ala Lys Gly Leu Asn Val Lys His Tyr Lys Ile Arg
195 200 205
Lys Leu Asp Ser Gly Gly Phe Tyr Ile Thr Ser Arg Thr Gln Phe Asn
210 215 220
Ser Leu Gln Gln Leu Val Ala Tyr Tyr Ser Lys His Ala Asp Gly Leu
225 230 235 240
Cys His Arg Leu Thr Thr Val Cys Pro Thr Ser Lys Pro Gln Thr Gln
245 250 255
Gly Leu Ala Lys Asp Ala Trp Glu Ile Pro Arg Glu Ser Leu Arg Leu
260 265 270
Glu Val Lys Leu Gly Gln Gly Cys Phe Gly Glu Val Trp Met Gly Thr
275 280 285
Trp Asn Gly Thr Thr Arg Val Ala Ile Lys Thr Leu Lys Pro Gly Thr
290 295 300
Met Ser Pro Glu Ala Phe Leu Gln Glu Ala Gln Val Met Lys Lys Leu
305 310 315 320
Arg His Glu Lys Leu Val Gln Leu Tyr Ala Val Val Ser Glu Glu Pro
325 330 335
Ile Tyr Ile Val Thr Glu Tyr Met Ser Lys Gly Ser Leu Leu Asp Phe
340 345 350
Leu Lys Gly Glu Thr Gly Lys Tyr Leu Arg Leu Pro Gln Leu Val Asp
355 360 365
Met Ala Ala Gln Ile Ala Ser Gly Met Ala Tyr Val Glu Arg Met Asn
370 375 380
Tyr Val His Arg Asp Leu Arg Ala Ala Asn Ile Leu Val Gly Glu Asn
385 390 395 400
Leu Val Cys Lys Val Ala Asp Phe Gly Leu Ala Arg Leu Ile Glu Asp
405 410 415
Asn Glu Tyr Thr Ala Arg Gln Gly Ala Lys Phe Pro Ile Lys Trp Thr
420 425 430
Ala Pro Glu Ala Ala Leu Tyr Gly Arg Phe Thr Ile Lys Ser Asp Val
435 440 445
Trp Ser Phe Gly Ile Leu Leu Thr Glu Leu Thr Thr Lys Gly Arg Val
450 455 460
Pro Tyr Pro Gly Met Val Asn Arg Glu Val Leu Asp Gln Val Glu Arg
465 470 475 480
Gly Tyr Arg Met Pro Cys Pro Pro Glu Cys Pro Glu Ser Leu His Asp
485 490 495
Leu Met Cys Gln Cys Trp Arg Lys Glu Pro Glu Glu Arg Pro Thr Phe
500 505 510
Glu Tyr Leu Gln Ala Phe Leu Glu Asp Tyr Phe Thr Ser Thr Glu Pro
515 520 525
Gln Tyr Gln Pro Gly Glu Asn Leu
530 535
<210> 164
<211> 536
<212> PRT
<213> 智人
<400> 164
Met Gly Ser Asn Lys Ser Lys Pro Lys Asp Ala Ser Gln Arg Arg Arg
1 5 10 15
Ser Leu Glu Pro Ala Glu Asn Val His Gly Ala Gly Gly Gly Ala Phe
20 25 30
Pro Ala Ser Gln Thr Pro Ser Lys Pro Ala Ser Ala Asp Gly His Arg
35 40 45
Gly Pro Ser Ala Ala Phe Ala Pro Ala Ala Ala Glu Pro Lys Leu Phe
50 55 60
Gly Gly Phe Asn Ser Ser Asp Thr Val Thr Ser Pro Gln Arg Ala Gly
65 70 75 80
Pro Leu Ala Gly Gly Val Thr Thr Phe Val Ala Leu Tyr Asp Tyr Glu
85 90 95
Ser Arg Thr Glu Thr Asp Leu Ser Phe Lys Lys Gly Glu Arg Leu Gln
100 105 110
Ile Val Asn Asn Thr Glu Gly Asp Trp Trp Leu Ala His Ser Leu Ser
115 120 125
Thr Gly Gln Thr Gly Tyr Ile Pro Ser Asn Tyr Val Ala Pro Ser Asp
130 135 140
Ser Ile Gln Ala Glu Glu Trp Tyr Phe Gly Lys Ile Thr Arg Arg Glu
145 150 155 160
Ser Glu Arg Leu Leu Leu Asn Ala Glu Asn Pro Arg Gly Thr Phe Leu
165 170 175
Val Arg Glu Ser Glu Thr Thr Lys Gly Ala Tyr Cys Leu Ser Val Ser
180 185 190
Asp Phe Asp Asn Ala Lys Gly Leu Asn Val Lys His Tyr Lys Ile Arg
195 200 205
Lys Leu Asp Ser Gly Gly Phe Tyr Ile Thr Ser Arg Thr Gln Phe Asn
210 215 220
Ser Leu Gln Gln Leu Val Ala Tyr Tyr Ser Lys His Ala Asp Gly Leu
225 230 235 240
Cys His Arg Leu Thr Thr Val Cys Pro Thr Ser Lys Pro Gln Thr Gln
245 250 255
Gly Leu Ala Lys Asp Ala Trp Glu Ile Pro Arg Glu Ser Leu Arg Leu
260 265 270
Glu Val Lys Leu Gly Gln Gly Cys Phe Gly Glu Val Trp Met Gly Thr
275 280 285
Trp Asn Gly Thr Thr Arg Val Ala Ile Lys Thr Leu Lys Pro Gly Thr
290 295 300
Met Ser Pro Glu Ala Phe Leu Gln Glu Ala Gln Val Met Lys Lys Leu
305 310 315 320
Arg His Glu Lys Leu Val Gln Leu Tyr Ala Val Val Ser Glu Glu Pro
325 330 335
Ile Tyr Ile Val Thr Glu Tyr Met Ser Lys Gly Ser Leu Leu Asp Phe
340 345 350
Leu Lys Gly Glu Thr Gly Lys Tyr Leu Arg Leu Pro Gln Leu Val Asp
355 360 365
Met Ala Ala Gln Ile Ala Ser Gly Met Ala Tyr Val Glu Arg Met Asn
370 375 380
Tyr Val His Arg Asp Leu Arg Ala Ala Asn Ile Leu Val Gly Glu Asn
385 390 395 400
Leu Val Cys Lys Val Ala Asp Phe Gly Leu Ala Arg Leu Ile Glu Asp
405 410 415
Asn Glu Tyr Thr Ala Arg Gln Gly Ala Lys Phe Pro Ile Lys Trp Thr
420 425 430
Ala Pro Glu Ala Ala Leu Tyr Gly Arg Phe Thr Ile Lys Ser Asp Val
435 440 445
Trp Ser Phe Gly Ile Leu Leu Thr Glu Leu Thr Thr Lys Gly Arg Val
450 455 460
Pro Tyr Pro Gly Met Val Asn Arg Glu Val Leu Asp Gln Val Glu Arg
465 470 475 480
Gly Tyr Arg Met Pro Cys Pro Pro Glu Cys Pro Glu Ser Leu His Asp
485 490 495
Leu Met Cys Gln Cys Trp Arg Lys Glu Pro Glu Glu Arg Pro Thr Phe
500 505 510
Glu Tyr Leu Gln Ala Phe Leu Glu Asp Tyr Phe Thr Ser Thr Glu Pro
515 520 525
Gln Tyr Gln Pro Gly Glu Asn Leu
530 535
<210> 165
<211> 623
<212> PRT
<213> 智人
<400> 165
Met Ala Thr Glu His Val Asn Gly Asn Gly Thr Glu Glu Pro Met Asp
1 5 10 15
Thr Thr Ser Ala Val Ile His Ser Glu Asn Phe Gln Thr Leu Leu Asp
20 25 30
Ala Gly Leu Pro Gln Lys Val Ala Glu Lys Leu Asp Glu Ile Tyr Val
35 40 45
Ala Gly Leu Val Ala His Ser Asp Leu Asp Glu Arg Ala Ile Glu Ala
50 55 60
Leu Lys Glu Phe Asn Glu Asp Gly Ala Leu Ala Val Leu Gln Gln Phe
65 70 75 80
Lys Asp Ser Asp Leu Ser His Val Gln Asn Lys Ser Ala Phe Leu Cys
85 90 95
Gly Val Met Lys Thr Tyr Arg Gln Arg Glu Lys Gln Gly Thr Lys Val
100 105 110
Ala Asp Ser Ser Lys Gly Pro Asp Glu Ala Lys Ile Lys Ala Leu Leu
115 120 125
Glu Arg Thr Gly Tyr Thr Leu Asp Val Thr Thr Gly Gln Arg Lys Tyr
130 135 140
Gly Gly Pro Pro Pro Asp Ser Val Tyr Ser Gly Gln Gln Pro Ser Val
145 150 155 160
Gly Thr Glu Ile Phe Val Gly Lys Ile Pro Arg Asp Leu Phe Glu Asp
165 170 175
Glu Leu Val Pro Leu Phe Glu Lys Ala Gly Pro Ile Trp Asp Leu Arg
180 185 190
Leu Met Met Asp Pro Leu Thr Gly Leu Asn Arg Gly Tyr Ala Phe Val
195 200 205
Thr Phe Cys Thr Lys Glu Ala Ala Gln Glu Ala Val Lys Leu Tyr Asn
210 215 220
Asn His Glu Ile Arg Ser Gly Lys His Ile Gly Val Cys Ile Ser Val
225 230 235 240
Ala Asn Asn Arg Leu Phe Val Gly Ser Ile Pro Lys Ser Lys Thr Lys
245 250 255
Glu Gln Ile Leu Glu Glu Phe Ser Lys Val Thr Glu Gly Leu Thr Asp
260 265 270
Val Ile Leu Tyr His Gln Pro Asp Asp Lys Lys Lys Asn Arg Gly Phe
275 280 285
Cys Phe Leu Glu Tyr Glu Asp His Lys Thr Ala Ala Gln Ala Arg Arg
290 295 300
Arg Leu Met Ser Gly Lys Val Lys Val Trp Gly Asn Val Gly Thr Val
305 310 315 320
Glu Trp Ala Asp Pro Ile Glu Asp Pro Asp Pro Glu Val Met Ala Lys
325 330 335
Val Lys Val Leu Phe Val Arg Asn Leu Ala Asn Thr Val Thr Glu Glu
340 345 350
Ile Leu Glu Lys Ala Phe Ser Gln Phe Gly Lys Leu Glu Arg Val Lys
355 360 365
Lys Leu Lys Asp Tyr Ala Phe Ile His Phe Asp Glu Arg Asp Gly Ala
370 375 380
Val Lys Ala Met Glu Glu Met Asn Gly Lys Asp Leu Glu Gly Glu Asn
385 390 395 400
Ile Glu Ile Val Phe Ala Lys Pro Pro Asp Gln Lys Arg Lys Glu Arg
405 410 415
Lys Ala Gln Arg Gln Ala Ala Lys Asn Gln Met Tyr Asp Asp Tyr Tyr
420 425 430
Tyr Tyr Gly Pro Pro His Met Pro Pro Pro Thr Arg Gly Arg Gly Arg
435 440 445
Gly Gly Arg Gly Gly Tyr Gly Tyr Pro Pro Asp Tyr Tyr Gly Tyr Glu
450 455 460
Asp Tyr Tyr Asp Tyr Tyr Gly Tyr Asp Tyr His Asn Tyr Arg Gly Gly
465 470 475 480
Tyr Glu Asp Pro Tyr Tyr Gly Tyr Glu Asp Phe Gln Val Gly Ala Arg
485 490 495
Gly Arg Gly Gly Arg Gly Ala Arg Gly Ala Ala Pro Ser Arg Gly Arg
500 505 510
Gly Ala Ala Pro Pro Arg Gly Arg Ala Gly Tyr Ser Gln Arg Gly Gly
515 520 525
Pro Gly Ser Ala Arg Gly Val Arg Gly Ala Arg Gly Gly Ala Gln Gln
530 535 540
Gln Arg Gly Arg Gly Val Arg Gly Ala Arg Gly Gly Arg Gly Gly Asn
545 550 555 560
Val Gly Gly Lys Arg Lys Ala Asp Gly Tyr Asn Gln Pro Asp Ser Lys
565 570 575
Arg Arg Gln Thr Asn Asn Gln Asn Trp Gly Ser Gln Pro Ile Ala Gln
580 585 590
Gln Pro Leu Gln Gly Gly Asp His Ser Gly Asn Tyr Gly Tyr Lys Ser
595 600 605
Glu Asn Gln Glu Phe Tyr Gln Asp Thr Phe Gly Gln Gln Trp Lys
610 615 620
<210> 166
<211> 331
<212> PRT
<213> 智人
<400> 166
Met Thr Glu Arg Pro Pro Ser Glu Ala Ala Arg Ser Asp Pro Gln Leu
1 5 10 15
Glu Gly Arg Asp Ala Ala Glu Ala Ser Met Ala Pro Pro His Leu Val
20 25 30
Leu Leu Asn Gly Val Ala Lys Glu Thr Ser Arg Ala Ala Ala Ala Glu
35 40 45
Pro Pro Val Ile Glu Leu Gly Ala Arg Gly Gly Pro Gly Gly Gly Pro
50 55 60
Ala Gly Gly Gly Gly Ala Ala Arg Asp Leu Lys Gly Arg Asp Ala Ala
65 70 75 80
Thr Ala Glu Ala Arg His Arg Val Pro Thr Thr Glu Leu Cys Arg Pro
85 90 95
Pro Gly Pro Ala Pro Ala Pro Ala Pro Ala Ser Val Thr Ala Glu Leu
100 105 110
Pro Gly Asp Gly Arg Met Val Gln Leu Ser Pro Pro Ala Leu Ala Ala
115 120 125
Pro Ala Ala Pro Gly Arg Ala Leu Leu Tyr Ser Leu Ser Gln Pro Leu
130 135 140
Ala Ser Leu Gly Ser Gly Phe Phe Gly Glu Pro Asp Ala Phe Pro Met
145 150 155 160
Phe Thr Thr Asn Asn Arg Val Lys Arg Arg Pro Ser Pro Tyr Glu Met
165 170 175
Glu Ile Thr Asp Gly Pro His Thr Lys Val Val Arg Arg Ile Phe Thr
180 185 190
Asn Ser Arg Glu Arg Trp Arg Gln Gln Asn Val Asn Gly Ala Phe Ala
195 200 205
Glu Leu Arg Lys Leu Ile Pro Thr His Pro Pro Asp Lys Lys Leu Ser
210 215 220
Lys Asn Glu Ile Leu Arg Leu Ala Met Lys Tyr Ile Asn Phe Leu Ala
225 230 235 240
Lys Leu Leu Asn Asp Gln Glu Glu Glu Gly Thr Gln Arg Ala Lys Thr
245 250 255
Gly Lys Asp Pro Val Val Gly Ala Gly Gly Gly Gly Gly Gly Gly Gly
260 265 270
Gly Gly Ala Pro Pro Asp Asp Leu Leu Gln Asp Val Leu Ser Pro Asn
275 280 285
Ser Ser Cys Gly Ser Ser Leu Asp Gly Ala Ala Ser Pro Asp Ser Tyr
290 295 300
Thr Glu Glu Pro Ala Pro Lys His Thr Ala Arg Ser Leu His Pro Ala
305 310 315 320
Met Leu Pro Ala Ala Asp Gly Ala Gly Pro Arg
325 330
<210> 167
<211> 698
<212> PRT
<213> 智人
<400> 167
Met Arg Leu Ala Val Gly Ala Leu Leu Val Cys Ala Val Leu Gly Leu
1 5 10 15
Cys Leu Ala Val Pro Asp Lys Thr Val Arg Trp Cys Ala Val Ser Glu
20 25 30
His Glu Ala Thr Lys Cys Gln Ser Phe Arg Asp His Met Lys Ser Val
35 40 45
Ile Pro Ser Asp Gly Pro Ser Val Ala Cys Val Lys Lys Ala Ser Tyr
50 55 60
Leu Asp Cys Ile Arg Ala Ile Ala Ala Asn Glu Ala Asp Ala Val Thr
65 70 75 80
Leu Asp Ala Gly Leu Val Tyr Asp Ala Tyr Leu Ala Pro Asn Asn Leu
85 90 95
Lys Pro Val Val Ala Glu Phe Tyr Gly Ser Lys Glu Asp Pro Gln Thr
100 105 110
Phe Tyr Tyr Ala Val Ala Val Val Lys Lys Asp Ser Gly Phe Gln Met
115 120 125
Asn Gln Leu Arg Gly Lys Lys Ser Cys His Thr Gly Leu Gly Arg Ser
130 135 140
Ala Gly Trp Asn Ile Pro Ile Gly Leu Leu Tyr Cys Asp Leu Pro Glu
145 150 155 160
Pro Arg Lys Pro Leu Glu Lys Ala Val Ala Asn Phe Phe Ser Gly Ser
165 170 175
Cys Ala Pro Cys Ala Asp Gly Thr Asp Phe Pro Gln Leu Cys Gln Leu
180 185 190
Cys Pro Gly Cys Gly Cys Ser Thr Leu Asn Gln Tyr Phe Gly Tyr Ser
195 200 205
Gly Ala Phe Lys Cys Leu Lys Asp Gly Ala Gly Asp Val Ala Phe Val
210 215 220
Lys His Ser Thr Ile Phe Glu Asn Leu Ala Asn Lys Ala Asp Arg Asp
225 230 235 240
Gln Tyr Glu Leu Leu Cys Leu Asp Asn Thr Arg Lys Pro Val Asp Glu
245 250 255
Tyr Lys Asp Cys His Leu Ala Gln Val Pro Ser His Thr Val Val Ala
260 265 270
Arg Ser Met Gly Gly Lys Glu Asp Leu Ile Trp Glu Leu Leu Asn Gln
275 280 285
Ala Gln Glu His Phe Gly Lys Asp Lys Ser Lys Glu Phe Gln Leu Phe
290 295 300
Ser Ser Pro His Gly Lys Asp Leu Leu Phe Lys Asp Ser Ala His Gly
305 310 315 320
Phe Leu Lys Val Pro Pro Arg Met Asp Ala Lys Met Tyr Leu Gly Tyr
325 330 335
Glu Tyr Val Thr Ala Ile Arg Asn Leu Arg Glu Gly Thr Cys Pro Glu
340 345 350
Ala Pro Thr Asp Glu Cys Lys Pro Val Lys Trp Cys Ala Leu Ser His
355 360 365
His Glu Arg Leu Lys Cys Asp Glu Trp Ser Val Asn Ser Val Gly Lys
370 375 380
Ile Glu Cys Val Ser Ala Glu Thr Thr Glu Asp Cys Ile Ala Lys Ile
385 390 395 400
Met Asn Gly Glu Ala Asp Ala Met Ser Leu Asp Gly Gly Phe Val Tyr
405 410 415
Ile Ala Gly Lys Cys Gly Leu Val Pro Val Leu Ala Glu Asn Tyr Asn
420 425 430
Lys Ser Asp Asn Cys Glu Asp Thr Pro Glu Ala Gly Tyr Phe Ala Ile
435 440 445
Ala Val Val Lys Lys Ser Ala Ser Asp Leu Thr Trp Asp Asn Leu Lys
450 455 460
Gly Lys Lys Ser Cys His Thr Ala Val Gly Arg Thr Ala Gly Trp Asn
465 470 475 480
Ile Pro Met Gly Leu Leu Tyr Asn Lys Ile Asn His Cys Arg Phe Asp
485 490 495
Glu Phe Phe Ser Glu Gly Cys Ala Pro Gly Ser Lys Lys Asp Ser Ser
500 505 510
Leu Cys Lys Leu Cys Met Gly Ser Gly Leu Asn Leu Cys Glu Pro Asn
515 520 525
Asn Lys Glu Gly Tyr Tyr Gly Tyr Thr Gly Ala Phe Arg Cys Leu Val
530 535 540
Glu Lys Gly Asp Val Ala Phe Val Lys His Gln Thr Val Pro Gln Asn
545 550 555 560
Thr Gly Gly Lys Asn Pro Asp Pro Trp Ala Lys Asn Leu Asn Glu Lys
565 570 575
Asp Tyr Glu Leu Leu Cys Leu Asp Gly Thr Arg Lys Pro Val Glu Glu
580 585 590
Tyr Ala Asn Cys His Leu Ala Arg Ala Pro Asn His Ala Val Val Thr
595 600 605
Arg Lys Asp Lys Glu Ala Cys Val His Lys Ile Leu Arg Gln Gln Gln
610 615 620
His Leu Phe Gly Ser Asn Val Thr Asp Cys Ser Gly Asn Phe Cys Leu
625 630 635 640
Phe Arg Ser Glu Thr Lys Asp Leu Leu Phe Arg Asp Asp Thr Val Cys
645 650 655
Leu Ala Lys Leu His Asp Arg Asn Thr Tyr Glu Lys Tyr Leu Gly Glu
660 665 670
Glu Tyr Val Lys Ala Val Gly Asn Leu Arg Lys Cys Ser Thr Ser Ser
675 680 685
Leu Leu Glu Ala Cys Thr Phe Arg Arg Pro
690 695
<210> 168
<211> 1170
<212> PRT
<213> 智人
<400> 168
Met Gly Leu Ala Trp Gly Leu Gly Val Leu Phe Leu Met His Val Cys
1 5 10 15
Gly Thr Asn Arg Ile Pro Glu Ser Gly Gly Asp Asn Ser Val Phe Asp
20 25 30
Ile Phe Glu Leu Thr Gly Ala Ala Arg Lys Gly Ser Gly Arg Arg Leu
35 40 45
Val Lys Gly Pro Asp Pro Ser Ser Pro Ala Phe Arg Ile Glu Asp Ala
50 55 60
Asn Leu Ile Pro Pro Val Pro Asp Asp Lys Phe Gln Asp Leu Val Asp
65 70 75 80
Ala Val Arg Ala Glu Lys Gly Phe Leu Leu Leu Ala Ser Leu Arg Gln
85 90 95
Met Lys Lys Thr Arg Gly Thr Leu Leu Ala Leu Glu Arg Lys Asp His
100 105 110
Ser Gly Gln Val Phe Ser Val Val Ser Asn Gly Lys Ala Gly Thr Leu
115 120 125
Asp Leu Ser Leu Thr Val Gln Gly Lys Gln His Val Val Ser Val Glu
130 135 140
Glu Ala Leu Leu Ala Thr Gly Gln Trp Lys Ser Ile Thr Leu Phe Val
145 150 155 160
Gln Glu Asp Arg Ala Gln Leu Tyr Ile Asp Cys Glu Lys Met Glu Asn
165 170 175
Ala Glu Leu Asp Val Pro Ile Gln Ser Val Phe Thr Arg Asp Leu Ala
180 185 190
Ser Ile Ala Arg Leu Arg Ile Ala Lys Gly Gly Val Asn Asp Asn Phe
195 200 205
Gln Gly Val Leu Gln Asn Val Arg Phe Val Phe Gly Thr Thr Pro Glu
210 215 220
Asp Ile Leu Arg Asn Lys Gly Cys Ser Ser Ser Thr Ser Val Leu Leu
225 230 235 240
Thr Leu Asp Asn Asn Val Val Asn Gly Ser Ser Pro Ala Ile Arg Thr
245 250 255
Asn Tyr Ile Gly His Lys Thr Lys Asp Leu Gln Ala Ile Cys Gly Ile
260 265 270
Ser Cys Asp Glu Leu Ser Ser Met Val Leu Glu Leu Arg Gly Leu Arg
275 280 285
Thr Ile Val Thr Thr Leu Gln Asp Ser Ile Arg Lys Val Thr Glu Glu
290 295 300
Asn Lys Glu Leu Ala Asn Glu Leu Arg Arg Pro Pro Leu Cys Tyr His
305 310 315 320
Asn Gly Val Gln Tyr Arg Asn Asn Glu Glu Trp Thr Val Asp Ser Cys
325 330 335
Thr Glu Cys His Cys Gln Asn Ser Val Thr Ile Cys Lys Lys Val Ser
340 345 350
Cys Pro Ile Met Pro Cys Ser Asn Ala Thr Val Pro Asp Gly Glu Cys
355 360 365
Cys Pro Arg Cys Trp Pro Ser Asp Ser Ala Asp Asp Gly Trp Ser Pro
370 375 380
Trp Ser Glu Trp Thr Ser Cys Ser Thr Ser Cys Gly Asn Gly Ile Gln
385 390 395 400
Gln Arg Gly Arg Ser Cys Asp Ser Leu Asn Asn Arg Cys Glu Gly Ser
405 410 415
Ser Val Gln Thr Arg Thr Cys His Ile Gln Glu Cys Asp Lys Arg Phe
420 425 430
Lys Gln Asp Gly Gly Trp Ser His Trp Ser Pro Trp Ser Ser Cys Ser
435 440 445
Val Thr Cys Gly Asp Gly Val Ile Thr Arg Ile Arg Leu Cys Asn Ser
450 455 460
Pro Ser Pro Gln Met Asn Gly Lys Pro Cys Glu Gly Glu Ala Arg Glu
465 470 475 480
Thr Lys Ala Cys Lys Lys Asp Ala Cys Pro Ile Asn Gly Gly Trp Gly
485 490 495
Pro Trp Ser Pro Trp Asp Ile Cys Ser Val Thr Cys Gly Gly Gly Val
500 505 510
Gln Lys Arg Ser Arg Leu Cys Asn Asn Pro Thr Pro Gln Phe Gly Gly
515 520 525
Lys Asp Cys Val Gly Asp Val Thr Glu Asn Gln Ile Cys Asn Lys Gln
530 535 540
Asp Cys Pro Ile Asp Gly Cys Leu Ser Asn Pro Cys Phe Ala Gly Val
545 550 555 560
Lys Cys Thr Ser Tyr Pro Asp Gly Ser Trp Lys Cys Gly Ala Cys Pro
565 570 575
Pro Gly Tyr Ser Gly Asn Gly Ile Gln Cys Thr Asp Val Asp Glu Cys
580 585 590
Lys Glu Val Pro Asp Ala Cys Phe Asn His Asn Gly Glu His Arg Cys
595 600 605
Glu Asn Thr Asp Pro Gly Tyr Asn Cys Leu Pro Cys Pro Pro Arg Phe
610 615 620
Thr Gly Ser Gln Pro Phe Gly Gln Gly Val Glu His Ala Thr Ala Asn
625 630 635 640
Lys Gln Val Cys Lys Pro Arg Asn Pro Cys Thr Asp Gly Thr His Asp
645 650 655
Cys Asn Lys Asn Ala Lys Cys Asn Tyr Leu Gly His Tyr Ser Asp Pro
660 665 670
Met Tyr Arg Cys Glu Cys Lys Pro Gly Tyr Ala Gly Asn Gly Ile Ile
675 680 685
Cys Gly Glu Asp Thr Asp Leu Asp Gly Trp Pro Asn Glu Asn Leu Val
690 695 700
Cys Val Ala Asn Ala Thr Tyr His Cys Lys Lys Asp Asn Cys Pro Asn
705 710 715 720
Leu Pro Asn Ser Gly Gln Glu Asp Tyr Asp Lys Asp Gly Ile Gly Asp
725 730 735
Ala Cys Asp Asp Asp Asp Asp Asn Asp Lys Ile Pro Asp Asp Arg Asp
740 745 750
Asn Cys Pro Phe His Tyr Asn Pro Ala Gln Tyr Asp Tyr Asp Arg Asp
755 760 765
Asp Val Gly Asp Arg Cys Asp Asn Cys Pro Tyr Asn His Asn Pro Asp
770 775 780
Gln Ala Asp Thr Asp Asn Asn Gly Glu Gly Asp Ala Cys Ala Ala Asp
785 790 795 800
Ile Asp Gly Asp Gly Ile Leu Asn Glu Arg Asp Asn Cys Gln Tyr Val
805 810 815
Tyr Asn Val Asp Gln Arg Asp Thr Asp Met Asp Gly Val Gly Asp Gln
820 825 830
Cys Asp Asn Cys Pro Leu Glu His Asn Pro Asp Gln Leu Asp Ser Asp
835 840 845
Ser Asp Arg Ile Gly Asp Thr Cys Asp Asn Asn Gln Asp Ile Asp Glu
850 855 860
Asp Gly His Gln Asn Asn Leu Asp Asn Cys Pro Tyr Val Pro Asn Ala
865 870 875 880
Asn Gln Ala Asp His Asp Lys Asp Gly Lys Gly Asp Ala Cys Asp His
885 890 895
Asp Asp Asp Asn Asp Gly Ile Pro Asp Asp Lys Asp Asn Cys Arg Leu
900 905 910
Val Pro Asn Pro Asp Gln Lys Asp Ser Asp Gly Asp Gly Arg Gly Asp
915 920 925
Ala Cys Lys Asp Asp Phe Asp His Asp Ser Val Pro Asp Ile Asp Asp
930 935 940
Ile Cys Pro Glu Asn Val Asp Ile Ser Glu Thr Asp Phe Arg Arg Phe
945 950 955 960
Gln Met Ile Pro Leu Asp Pro Lys Gly Thr Ser Gln Asn Asp Pro Asn
965 970 975
Trp Val Val Arg His Gln Gly Lys Glu Leu Val Gln Thr Val Asn Cys
980 985 990
Asp Pro Gly Leu Ala Val Gly Tyr Asp Glu Phe Asn Ala Val Asp Phe
995 1000 1005
Ser Gly Thr Phe Phe Ile Asn Thr Glu Arg Asp Asp Asp Tyr Ala
1010 1015 1020
Gly Phe Val Phe Gly Tyr Gln Ser Ser Ser Arg Phe Tyr Val Val
1025 1030 1035
Met Trp Lys Gln Val Thr Gln Ser Tyr Trp Asp Thr Asn Pro Thr
1040 1045 1050
Arg Ala Gln Gly Tyr Ser Gly Leu Ser Val Lys Val Val Asn Ser
1055 1060 1065
Thr Thr Gly Pro Gly Glu His Leu Arg Asn Ala Leu Trp His Thr
1070 1075 1080
Gly Asn Thr Pro Gly Gln Val Arg Thr Leu Trp His Asp Pro Arg
1085 1090 1095
His Ile Gly Trp Lys Asp Phe Thr Ala Tyr Arg Trp Arg Leu Ser
1100 1105 1110
His Arg Pro Lys Thr Gly Phe Ile Arg Val Val Met Tyr Glu Gly
1115 1120 1125
Lys Lys Ile Met Ala Asp Ser Gly Pro Ile Tyr Asp Lys Thr Tyr
1130 1135 1140
Ala Gly Gly Arg Leu Gly Leu Phe Val Phe Ser Gln Glu Met Val
1145 1150 1155
Phe Phe Ser Asp Leu Lys Tyr Glu Cys Arg Asp Pro
1160 1165 1170
<210> 169
<211> 207
<212> PRT
<213> 智人
<400> 169
Met Ala Pro Phe Glu Pro Leu Ala Ser Gly Ile Leu Leu Leu Leu Trp
1 5 10 15
Leu Ile Ala Pro Ser Arg Ala Cys Thr Cys Val Pro Pro His Pro Gln
20 25 30
Thr Ala Phe Cys Asn Ser Asp Leu Val Ile Arg Ala Lys Phe Val Gly
35 40 45
Thr Pro Glu Val Asn Gln Thr Thr Leu Tyr Gln Arg Tyr Glu Ile Lys
50 55 60
Met Thr Lys Met Tyr Lys Gly Phe Gln Ala Leu Gly Asp Ala Ala Asp
65 70 75 80
Ile Arg Phe Val Tyr Thr Pro Ala Met Glu Ser Val Cys Gly Tyr Phe
85 90 95
His Arg Ser His Asn Arg Ser Glu Glu Phe Leu Ile Ala Gly Lys Leu
100 105 110
Gln Asp Gly Leu Leu His Ile Thr Thr Cys Ser Phe Val Ala Pro Trp
115 120 125
Asn Ser Leu Ser Leu Ala Gln Arg Arg Gly Phe Thr Lys Thr Tyr Thr
130 135 140
Val Gly Cys Glu Glu Cys Thr Val Phe Pro Cys Leu Ser Ile Pro Cys
145 150 155 160
Lys Leu Gln Ser Gly Thr His Cys Leu Trp Thr Asp Gln Leu Leu Gln
165 170 175
Gly Ser Glu Lys Gly Phe Gln Ser Arg His Leu Ala Cys Leu Pro Arg
180 185 190
Glu Pro Gly Leu Cys Thr Trp Gln Ser Leu Arg Ser Gln Ile Ala
195 200 205
<210> 170
<211> 623
<212> PRT
<213> 智人
<400> 170
Met Glu Ser Tyr His Lys Pro Asp Gln Gln Lys Leu Gln Ala Leu Lys
1 5 10 15
Asp Thr Ala Asn Arg Leu Arg Ile Ser Ser Ile Gln Ala Thr Thr Ala
20 25 30
Ala Gly Ser Gly His Pro Thr Ser Cys Cys Ser Ala Ala Glu Ile Met
35 40 45
Ala Val Leu Phe Phe His Thr Met Arg Tyr Lys Ser Gln Asp Pro Arg
50 55 60
Asn Pro His Asn Asp Arg Phe Val Leu Ser Lys Gly His Ala Ala Pro
65 70 75 80
Ile Leu Tyr Ala Val Trp Ala Glu Ala Gly Phe Leu Ala Glu Ala Glu
85 90 95
Leu Leu Asn Leu Arg Lys Ile Ser Ser Asp Leu Asp Gly His Pro Val
100 105 110
Pro Lys Gln Ala Phe Thr Asp Val Ala Thr Gly Ser Leu Gly Gln Gly
115 120 125
Leu Gly Ala Ala Cys Gly Met Ala Tyr Thr Gly Lys Tyr Phe Asp Lys
130 135 140
Ala Ser Tyr Arg Val Tyr Cys Leu Leu Gly Asp Gly Glu Leu Ser Glu
145 150 155 160
Gly Ser Val Trp Glu Ala Met Ala Phe Ala Ser Ile Tyr Lys Leu Asp
165 170 175
Asn Leu Val Ala Ile Leu Asp Ile Asn Arg Leu Gly Gln Ser Asp Pro
180 185 190
Ala Pro Leu Gln His Gln Met Asp Ile Tyr Gln Lys Arg Cys Glu Ala
195 200 205
Phe Gly Trp His Ala Ile Ile Val Asp Gly His Ser Val Glu Glu Leu
210 215 220
Cys Lys Ala Phe Gly Gln Ala Lys His Gln Pro Thr Ala Ile Ile Ala
225 230 235 240
Lys Thr Phe Lys Gly Arg Gly Ile Thr Gly Val Glu Asp Lys Glu Ser
245 250 255
Trp His Gly Lys Pro Leu Pro Lys Asn Met Ala Glu Gln Ile Ile Gln
260 265 270
Glu Ile Tyr Ser Gln Ile Gln Ser Lys Lys Lys Ile Leu Ala Thr Pro
275 280 285
Pro Gln Glu Asp Ala Pro Ser Val Asp Ile Ala Asn Ile Arg Met Pro
290 295 300
Ser Leu Pro Ser Tyr Lys Val Gly Asp Lys Ile Ala Thr Arg Lys Ala
305 310 315 320
Tyr Gly Gln Ala Leu Ala Lys Leu Gly His Ala Ser Asp Arg Ile Ile
325 330 335
Ala Leu Asp Gly Asp Thr Lys Asn Ser Thr Phe Ser Glu Ile Phe Lys
340 345 350
Lys Glu His Pro Asp Arg Phe Ile Glu Cys Tyr Ile Ala Glu Gln Asn
355 360 365
Met Val Ser Ile Ala Val Gly Cys Ala Thr Arg Asn Arg Thr Val Pro
370 375 380
Phe Cys Ser Thr Phe Ala Ala Phe Phe Thr Arg Ala Phe Asp Gln Ile
385 390 395 400
Arg Met Ala Ala Ile Ser Glu Ser Asn Ile Asn Leu Cys Gly Ser His
405 410 415
Cys Gly Val Ser Ile Gly Glu Asp Gly Pro Ser Gln Met Ala Leu Glu
420 425 430
Asp Leu Ala Met Phe Arg Ser Val Pro Thr Ser Thr Val Phe Tyr Pro
435 440 445
Ser Asp Gly Val Ala Thr Glu Lys Ala Val Glu Leu Ala Ala Asn Thr
450 455 460
Lys Gly Ile Cys Phe Ile Arg Thr Ser Arg Pro Glu Asn Ala Ile Ile
465 470 475 480
Tyr Asn Asn Asn Glu Asp Phe Gln Val Gly Gln Ala Lys Val Val Leu
485 490 495
Lys Ser Lys Asp Asp Gln Val Thr Val Ile Gly Ala Gly Val Thr Leu
500 505 510
His Glu Ala Leu Ala Ala Ala Glu Leu Leu Lys Lys Glu Lys Ile Asn
515 520 525
Ile Arg Val Leu Asp Pro Phe Thr Ile Lys Pro Leu Asp Arg Lys Leu
530 535 540
Ile Leu Asp Ser Ala Arg Ala Thr Lys Gly Arg Ile Leu Thr Val Glu
545 550 555 560
Asp His Tyr Tyr Glu Gly Gly Ile Gly Glu Ala Val Ser Ser Ala Val
565 570 575
Val Gly Glu Pro Gly Ile Thr Val Thr His Leu Ala Val Asn Arg Val
580 585 590
Pro Arg Ser Gly Lys Pro Ala Glu Leu Leu Lys Met Phe Gly Ile Asp
595 600 605
Arg Asp Ala Ile Ala Gln Ala Val Arg Gly Leu Ile Thr Lys Ala
610 615 620
<210> 171
<211> 277
<212> PRT
<213> 智人
<400> 171
Met Ile Ile Leu Ile Tyr Leu Phe Leu Leu Leu Trp Glu Asp Thr Gln
1 5 10 15
Gly Trp Gly Phe Lys Asp Gly Ile Phe His Asn Ser Ile Trp Leu Glu
20 25 30
Arg Ala Ala Gly Val Tyr His Arg Glu Ala Arg Ser Gly Lys Tyr Lys
35 40 45
Leu Thr Tyr Ala Glu Ala Lys Ala Val Cys Glu Phe Glu Gly Gly His
50 55 60
Leu Ala Thr Tyr Lys Gln Leu Glu Ala Ala Arg Lys Ile Gly Phe His
65 70 75 80
Val Cys Ala Ala Gly Trp Met Ala Lys Gly Arg Val Gly Tyr Pro Ile
85 90 95
Val Lys Pro Gly Pro Asn Cys Gly Phe Gly Lys Thr Gly Ile Ile Asp
100 105 110
Tyr Gly Ile Arg Leu Asn Arg Ser Glu Arg Trp Asp Ala Tyr Cys Tyr
115 120 125
Asn Pro His Ala Lys Glu Cys Gly Gly Val Phe Thr Asp Pro Lys Gln
130 135 140
Ile Phe Lys Ser Pro Gly Phe Pro Asn Glu Tyr Glu Asp Asn Gln Ile
145 150 155 160
Cys Tyr Trp His Ile Arg Leu Lys Tyr Gly Gln Arg Ile His Leu Ser
165 170 175
Phe Leu Asp Phe Asp Leu Glu Asp Asp Pro Gly Cys Leu Ala Asp Tyr
180 185 190
Val Glu Ile Tyr Asp Ser Tyr Asp Asp Val His Gly Phe Val Gly Arg
195 200 205
Tyr Cys Gly Asp Glu Leu Pro Asp Asp Ile Ile Ser Thr Gly Asn Val
210 215 220
Met Thr Leu Lys Phe Leu Ser Asp Ala Ser Val Thr Ala Gly Gly Phe
225 230 235 240
Gln Ile Lys Tyr Val Ala Met Asp Pro Val Ser Lys Ser Ser Gln Gly
245 250 255
Lys Asn Thr Ser Thr Thr Ser Thr Gly Asn Lys Asn Phe Leu Ala Gly
260 265 270
Arg Phe Ser His Leu
275
<210> 172
<211> 440
<212> PRT
<213> 智人
<400> 172
Met Glu Gln Arg Gly Gln Asn Ala Pro Ala Ala Ser Gly Ala Arg Lys
1 5 10 15
Arg His Gly Pro Gly Pro Arg Glu Ala Arg Gly Ala Arg Pro Gly Pro
20 25 30
Arg Val Pro Lys Thr Leu Val Leu Val Val Ala Ala Val Leu Leu Leu
35 40 45
Val Ser Ala Glu Ser Ala Leu Ile Thr Gln Gln Asp Leu Ala Pro Gln
50 55 60
Gln Arg Ala Ala Pro Gln Gln Lys Arg Ser Ser Pro Ser Glu Gly Leu
65 70 75 80
Cys Pro Pro Gly His His Ile Ser Glu Asp Gly Arg Asp Cys Ile Ser
85 90 95
Cys Lys Tyr Gly Gln Asp Tyr Ser Thr His Trp Asn Asp Leu Leu Phe
100 105 110
Cys Leu Arg Cys Thr Arg Cys Asp Ser Gly Glu Val Glu Leu Ser Pro
115 120 125
Cys Thr Thr Thr Arg Asn Thr Val Cys Gln Cys Glu Glu Gly Thr Phe
130 135 140
Arg Glu Glu Asp Ser Pro Glu Met Cys Arg Lys Cys Arg Thr Gly Cys
145 150 155 160
Pro Arg Gly Met Val Lys Val Gly Asp Cys Thr Pro Trp Ser Asp Ile
165 170 175
Glu Cys Val His Lys Glu Ser Gly Thr Lys His Ser Gly Glu Val Pro
180 185 190
Ala Val Glu Glu Thr Val Thr Ser Ser Pro Gly Thr Pro Ala Ser Pro
195 200 205
Cys Ser Leu Ser Gly Ile Ile Ile Gly Val Thr Val Ala Ala Val Val
210 215 220
Leu Ile Val Ala Val Phe Val Cys Lys Ser Leu Leu Trp Lys Lys Val
225 230 235 240
Leu Pro Tyr Leu Lys Gly Ile Cys Ser Gly Gly Gly Gly Asp Pro Glu
245 250 255
Arg Val Asp Arg Ser Ser Gln Arg Pro Gly Ala Glu Asp Asn Val Leu
260 265 270
Asn Glu Ile Val Ser Ile Leu Gln Pro Thr Gln Val Pro Glu Gln Glu
275 280 285
Met Glu Val Gln Glu Pro Ala Glu Pro Thr Gly Val Asn Met Leu Ser
290 295 300
Pro Gly Glu Ser Glu His Leu Leu Glu Pro Ala Glu Ala Glu Arg Ser
305 310 315 320
Gln Arg Arg Arg Leu Leu Val Pro Ala Asn Glu Gly Asp Pro Thr Glu
325 330 335
Thr Leu Arg Gln Cys Phe Asp Asp Phe Ala Asp Leu Val Pro Phe Asp
340 345 350
Ser Trp Glu Pro Leu Met Arg Lys Leu Gly Leu Met Asp Asn Glu Ile
355 360 365
Lys Val Ala Lys Ala Glu Ala Ala Gly His Arg Asp Thr Leu Tyr Thr
370 375 380
Met Leu Ile Lys Trp Val Asn Lys Thr Gly Arg Asp Ala Ser Val His
385 390 395 400
Thr Leu Leu Asp Ala Leu Glu Thr Leu Gly Glu Arg Leu Ala Lys Gln
405 410 415
Lys Ile Glu Asp His Leu Leu Ser Ser Gly Lys Phe Met Tyr Leu Glu
420 425 430
Gly Asn Ala Asp Ser Ala Met Ser
435 440
<210> 173
<211> 300
<212> PRT
<213> 智人
<400> 173
Met Arg Ala Leu Glu Gly Pro Gly Leu Ser Leu Leu Cys Leu Val Leu
1 5 10 15
Ala Leu Pro Ala Leu Leu Pro Val Pro Ala Val Arg Gly Val Ala Glu
20 25 30
Thr Pro Thr Tyr Pro Trp Arg Asp Ala Glu Thr Gly Glu Arg Leu Val
35 40 45
Cys Ala Gln Cys Pro Pro Gly Thr Phe Val Gln Arg Pro Cys Arg Arg
50 55 60
Asp Ser Pro Thr Thr Cys Gly Pro Cys Pro Pro Arg His Tyr Thr Gln
65 70 75 80
Phe Trp Asn Tyr Leu Glu Arg Cys Arg Tyr Cys Asn Val Leu Cys Gly
85 90 95
Glu Arg Glu Glu Glu Ala Arg Ala Cys His Ala Thr His Asn Arg Ala
100 105 110
Cys Arg Cys Arg Thr Gly Phe Phe Ala His Ala Gly Phe Cys Leu Glu
115 120 125
His Ala Ser Cys Pro Pro Gly Ala Gly Val Ile Ala Pro Gly Thr Pro
130 135 140
Ser Gln Asn Thr Gln Cys Gln Pro Cys Pro Pro Gly Thr Phe Ser Ala
145 150 155 160
Ser Ser Ser Ser Ser Glu Gln Cys Gln Pro His Arg Asn Cys Thr Ala
165 170 175
Leu Gly Leu Ala Leu Asn Val Pro Gly Ser Ser Ser His Asp Thr Leu
180 185 190
Cys Thr Ser Cys Thr Gly Phe Pro Leu Ser Thr Arg Val Pro Gly Ala
195 200 205
Glu Glu Cys Glu Arg Ala Val Ile Asp Phe Val Ala Phe Gln Asp Ile
210 215 220
Ser Ile Lys Arg Leu Gln Arg Leu Leu Gln Ala Leu Glu Ala Pro Glu
225 230 235 240
Gly Trp Gly Pro Thr Pro Arg Ala Gly Arg Ala Ala Leu Gln Leu Lys
245 250 255
Leu Arg Arg Arg Leu Thr Glu Leu Leu Gly Ala Gln Asp Gly Ala Leu
260 265 270
Leu Val Arg Leu Leu Gln Ala Leu Arg Val Ala Arg Met Pro Gly Leu
275 280 285
Glu Arg Ser Val Arg Glu Arg Phe Leu Pro Val His
290 295 300
<210> 174
<211> 393
<212> PRT
<213> 智人
<400> 174
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 Ile Arg Gly Arg Glu
325 330 335
Arg Phe Glu Met Phe Arg Glu Leu Asn Glu Ala Leu Glu Leu Lys Asp
340 345 350
Ala Gln Ala Gly Lys Glu Pro Gly Gly Ser Arg Ala His Ser Ser His
355 360 365
Leu Lys Ser Lys Lys Gly Gln Ser Thr Ser Arg His Lys Lys Leu Met
370 375 380
Phe Lys Thr Glu Gly Pro Asp Ser Asp
385 390
<210> 175
<211> 284
<212> PRT
<213> 智人
<400> 175
Met Asp Ala Ile Lys Lys Lys Met Gln Met Leu Lys Leu Asp Lys Glu
1 5 10 15
Asn Ala Ile Asp Arg Ala Glu Gln Ala Glu Ala Asp Lys Lys Gln Ala
20 25 30
Glu Asp Arg Cys Lys Gln Leu Glu Glu Glu Gln Gln Ala Leu Gln Lys
35 40 45
Lys Leu Lys Gly Thr Glu Asp Glu Val Glu Lys Tyr Ser Glu Ser Val
50 55 60
Lys Glu Ala Gln Glu Lys Leu Glu Gln Ala Glu Lys Lys Ala Thr Asp
65 70 75 80
Ala Glu Ala Asp Val Ala Ser Leu Asn Arg Arg Ile Gln Leu Val Glu
85 90 95
Glu Glu Leu Asp Arg Ala Gln Glu Arg Leu Ala Thr Ala Leu Gln Lys
100 105 110
Leu Glu Glu Ala Glu Lys Ala Ala Asp Glu Ser Glu Arg Gly Met Lys
115 120 125
Val Ile Glu Asn Arg Ala Met Lys Asp Glu Glu Lys Met Glu Leu Gln
130 135 140
Glu Met Gln Leu Lys Glu Ala Lys His Ile Ala Glu Asp Ser Asp Arg
145 150 155 160
Lys Tyr Glu Glu Val Ala Arg Lys Leu Val Ile Leu Glu Gly Glu Leu
165 170 175
Glu Arg Ser Glu Glu Arg Ala Glu Val Ala Glu Ser Lys Cys Gly Asp
180 185 190
Leu Glu Glu Glu Leu Lys Ile Val Thr Asn Asn Leu Lys Ser Leu Glu
195 200 205
Ala Gln Ala Asp Lys Tyr Ser Thr Lys Glu Asp Lys Tyr Glu Glu Glu
210 215 220
Ile Lys Leu Leu Glu Glu Lys Leu Lys Glu Ala Glu Thr Arg Ala Glu
225 230 235 240
Phe Ala Glu Arg Ser Val Ala Lys Leu Glu Lys Thr Ile Asp Asp Leu
245 250 255
Glu Asp Glu Val Tyr Ala Gln Lys Met Lys Tyr Lys Ala Ile Ser Glu
260 265 270
Glu Leu Asp Asn Ala Leu Asn Asp Ile Thr Ser Leu
275 280
<210> 176
<211> 172
<212> PRT
<213> 智人
<400> 176
Met Ile Ile Tyr Arg Asp Leu Ile Ser His Asp Glu Met Phe Ser Asp
1 5 10 15
Ile Tyr Lys Ile Arg Glu Ile Ala Asp Gly Leu Cys Leu Glu Val Glu
20 25 30
Gly Lys Met Val Ser Arg Thr Glu Gly Asn Ile Asp Asp Ser Leu Ile
35 40 45
Gly Gly Asn Ala Ser Ala Glu Gly Pro Glu Gly Glu Gly Thr Glu Ser
50 55 60
Thr Val Ile Thr Gly Val Asp Ile Val Met Asn His His Leu Gln Glu
65 70 75 80
Thr Ser Phe Thr Lys Glu Ala Tyr Lys Lys Tyr Ile Lys Asp Tyr Met
85 90 95
Lys Ser Ile Lys Gly Lys Leu Glu Glu Gln Arg Pro Glu Arg Val Lys
100 105 110
Pro Phe Met Thr Gly Ala Ala Glu Gln Ile Lys His Ile Leu Ala Asn
115 120 125
Phe Lys Asn Tyr Gln Phe Phe Ile Gly Glu Asn Met Asn Pro Asp Gly
130 135 140
Met Val Ala Leu Leu Asp Tyr Arg Glu Asp Gly Val Thr Pro Tyr Met
145 150 155 160
Ile Phe Phe Lys Asp Gly Leu Glu Met Glu Lys Cys
165 170
<210> 177
<211> 704
<212> PRT
<213> 智人
<400> 177
Met Ala Arg Glu Leu Arg Ala Leu Leu Leu Trp Gly Arg Arg Leu Arg
1 5 10 15
Pro Leu Leu Arg Ala Pro Ala Leu Ala Ala Val Pro Gly Gly Lys Pro
20 25 30
Ile Leu Cys Pro Arg Arg Thr Thr Ala Gln Leu Gly Pro Arg Arg Asn
35 40 45
Pro Ala Trp Ser Leu Gln Ala Gly Arg Leu Phe Ser Thr Gln Thr Ala
50 55 60
Glu Asp Lys Glu Glu Pro Leu His Ser Ile Ile Ser Ser Thr Glu Ser
65 70 75 80
Val Gln Gly Ser Thr Ser Lys His Glu Phe Gln Ala Glu Thr Lys Lys
85 90 95
Leu Leu Asp Ile Val Ala Arg Ser Leu Tyr Ser Glu Lys Glu Val Phe
100 105 110
Ile Arg Glu Leu Ile Ser Asn Ala Ser Asp Ala Leu Glu Lys Leu Arg
115 120 125
His Lys Leu Val Ser Asp Gly Gln Ala Leu Pro Glu Met Glu Ile His
130 135 140
Leu Gln Thr Asn Ala Glu Lys Gly Thr Ile Thr Ile Gln Asp Thr Gly
145 150 155 160
Ile Gly Met Thr Gln Glu Glu Leu Val Ser Asn Leu Gly Thr Ile Ala
165 170 175
Arg Ser Gly Ser Lys Ala Phe Leu Asp Ala Leu Gln Asn Gln Ala Glu
180 185 190
Ala Ser Ser Lys Ile Ile Gly Gln Phe Gly Val Gly Phe Tyr Ser Ala
195 200 205
Phe Met Val Ala Asp Arg Val Glu Val Tyr Ser Arg Ser Ala Ala Pro
210 215 220
Gly Ser Leu Gly Tyr Gln Trp Leu Ser Asp Gly Ser Gly Val Phe Glu
225 230 235 240
Ile Ala Glu Ala Ser Gly Val Arg Thr Gly Thr Lys Ile Ile Ile His
245 250 255
Leu Lys Ser Asp Cys Lys Glu Phe Ser Ser Glu Ala Arg Val Arg Asp
260 265 270
Val Val Thr Lys Tyr Ser Asn Phe Val Ser Phe Pro Leu Tyr Leu Asn
275 280 285
Gly Arg Arg Met Asn Thr Leu Gln Ala Ile Trp Met Met Asp Pro Lys
290 295 300
Asp Val Arg Glu Trp Gln His Glu Glu Phe Tyr Arg Tyr Val Ala Gln
305 310 315 320
Ala His Asp Lys Pro Arg Tyr Thr Leu His Tyr Lys Thr Asp Ala Pro
325 330 335
Leu Asn Ile Arg Ser Ile Phe Tyr Val Pro Asp Met Lys Pro Ser Met
340 345 350
Phe Asp Val Ser Arg Glu Leu Gly Ser Ser Val Ala Leu Tyr Ser Arg
355 360 365
Lys Val Leu Ile Gln Thr Lys Ala Thr Asp Ile Leu Pro Lys Trp Leu
370 375 380
Arg Phe Ile Arg Gly Val Val Asp Ser Glu Asp Ile Pro Leu Asn Leu
385 390 395 400
Ser Arg Glu Leu Leu Gln Glu Ser Ala Leu Ile Arg Lys Leu Arg Asp
405 410 415
Val Leu Gln Gln Arg Leu Ile Lys Phe Phe Ile Asp Gln Ser Lys Lys
420 425 430
Asp Ala Glu Lys Tyr Ala Lys Phe Phe Glu Asp Tyr Gly Leu Phe Met
435 440 445
Arg Glu Gly Ile Val Thr Ala Thr Glu Gln Glu Val Lys Glu Asp Ile
450 455 460
Ala Lys Leu Leu Arg Tyr Glu Ser Ser Ala Leu Pro Ser Gly Gln Leu
465 470 475 480
Thr Ser Leu Ser Glu Tyr Ala Ser Arg Met Arg Ala Gly Thr Arg Asn
485 490 495
Ile Tyr Tyr Leu Cys Ala Pro Asn Arg His Leu Ala Glu His Ser Pro
500 505 510
Tyr Tyr Glu Ala Met Lys Lys Lys Asp Thr Glu Val Leu Phe Cys Phe
515 520 525
Glu Gln Phe Asp Glu Leu Thr Leu Leu His Leu Arg Glu Phe Asp Lys
530 535 540
Lys Lys Leu Ile Ser Val Glu Thr Asp Ile Val Val Asp His Tyr Lys
545 550 555 560
Glu Glu Lys Phe Glu Asp Arg Ser Pro Ala Ala Glu Cys Leu Ser Glu
565 570 575
Lys Glu Thr Glu Glu Leu Met Ala Trp Met Arg Asn Val Leu Gly Ser
580 585 590
Arg Val Thr Asn Val Lys Val Thr Leu Arg Leu Asp Thr His Pro Ala
595 600 605
Met Val Thr Val Leu Glu Met Gly Ala Ala Arg His Phe Leu Arg Met
610 615 620
Gln Gln Leu Ala Lys Thr Gln Glu Glu Arg Ala Gln Leu Leu Gln Pro
625 630 635 640
Thr Leu Glu Ile Asn Pro Arg His Ala Leu Ile Lys Lys Leu Asn Gln
645 650 655
Leu Arg Ala Ser Glu Pro Gly Leu Ala Gln Leu Leu Val Asp Gln Ile
660 665 670
Tyr Glu Asn Ala Met Ile Ala Ala Gly Leu Val Asp Asp Pro Arg Ala
675 680 685
Met Val Gly Arg Leu Asn Glu Leu Leu Val Lys Ala Leu Glu Arg His
690 695 700
<210> 178
<211> 297
<212> PRT
<213> 智人
<400> 178
Met Val His Gln Val Leu Tyr Arg Ala Leu Val Ser Thr Lys Trp Leu
1 5 10 15
Ala Glu Ser Ile Arg Thr Gly Lys Leu Gly Pro Gly Leu Arg Val Leu
20 25 30
Asp Ala Ser Trp Tyr Ser Pro Gly Thr Arg Glu Ala Arg Lys Glu Tyr
35 40 45
Leu Glu Arg His Val Pro Gly Ala Ser Phe Phe Asp Ile Glu Glu Cys
50 55 60
Arg Asp Thr Ala Ser Pro Tyr Glu Met Met Leu Pro Ser Glu Ala Gly
65 70 75 80
Phe Ala Glu Tyr Val Gly Arg Leu Gly Ile Ser Asn His Thr His Val
85 90 95
Val Val Tyr Asp Gly Glu His Leu Gly Ser Phe Tyr Ala Pro Arg Val
100 105 110
Trp Trp Met Phe Arg Val Phe Gly His Arg Thr Val Ser Val Leu Asn
115 120 125
Gly Gly Phe Arg Asn Trp Leu Lys Glu Gly His Pro Val Thr Ser Glu
130 135 140
Pro Ser Arg Pro Glu Pro Ala Val Phe Lys Ala Thr Leu Asp Arg Ser
145 150 155 160
Leu Leu Lys Thr Tyr Glu Gln Val Leu Glu Asn Leu Glu Ser Lys Arg
165 170 175
Phe Gln Leu Val Asp Ser Arg Ser Gln Gly Arg Phe Leu Gly Thr Glu
180 185 190
Pro Glu Pro Asp Ala Val Gly Leu Asp Ser Gly His Ile Arg Gly Ala
195 200 205
Val Asn Met Pro Phe Met Asp Phe Leu Thr Glu Asp Gly Phe Glu Lys
210 215 220
Gly Pro Glu Glu Leu Arg Ala Leu Phe Gln Thr Lys Lys Val Asp Leu
225 230 235 240
Ser Gln Pro Leu Ile Ala Thr Cys Arg Lys Gly Val Thr Ala Cys His
245 250 255
Val Ala Leu Ala Ala Tyr Leu Cys Gly Lys Pro Asp Val Ala Val Tyr
260 265 270
Asp Gly Ser Trp Ser Glu Trp Phe Arg Arg Ala Pro Pro Glu Ser Arg
275 280 285
Val Ser Gln Gly Lys Ser Glu Lys Ala
290 295
<210> 179
<211> 451
<212> PRT
<213> 智人
<400> 179
Met Arg Glu Ile Val His Ile Gln Ile Gly Gln Cys Gly Asn Gln Ile
1 5 10 15
Gly Ala Lys Phe Trp Glu Met Ile Gly Glu Glu His Gly Ile Asp Leu
20 25 30
Ala Gly Ser Asp Arg Gly Ala Ser Ala Leu Gln Leu Glu Arg Ile Ser
35 40 45
Val Tyr Tyr Asn Glu Ala Tyr Gly Arg Lys Tyr Val Pro Arg Ala Val
50 55 60
Leu Val Asp Leu Glu Pro Gly Thr Met Asp Ser Ile Arg Ser Ser Lys
65 70 75 80
Leu Gly Ala Leu Phe Gln Pro Asp Ser Phe Val His Gly Asn Ser Gly
85 90 95
Ala Gly Asn Asn Trp Ala Lys Gly His Tyr Thr Glu Gly Ala Glu Leu
100 105 110
Ile Glu Asn Val Leu Glu Val Val Arg His Glu Ser Glu Ser Cys Asp
115 120 125
Cys Leu Gln Gly Phe Gln Ile Val His Ser Leu Gly Gly Gly Thr Gly
130 135 140
Ser Gly Met Gly Thr Leu Leu Met Asn Lys Ile Arg Glu Glu Tyr Pro
145 150 155 160
Asp Arg Ile Met Asn Ser Phe Ser Val Met Pro Ser Pro Lys Val Ser
165 170 175
Asp Thr Val Val Glu Pro Tyr Asn Ala Val Leu Ser Ile His Gln Leu
180 185 190
Ile Glu Asn Ala Asp Ala Cys Phe Cys Ile Asp Asn Glu Ala Leu Tyr
195 200 205
Asp Ile Cys Phe Arg Thr Leu Lys Leu Thr Thr Pro Thr Tyr Gly Asp
210 215 220
Leu Asn His Leu Val Ser Leu Thr Met Ser Gly Ile Thr Thr Ser Leu
225 230 235 240
Arg Phe Pro Gly Gln Leu Asn Ala Asp Leu Arg Lys Leu Ala Val Asn
245 250 255
Met Val Pro Phe Pro Arg Leu His Phe Phe Met Pro Gly Phe Ala Pro
260 265 270
Leu Thr Ala Gln Gly Ser Gln Gln Tyr Arg Ala Leu Ser Val Ala Glu
275 280 285
Leu Thr Gln Gln Met Phe Asp Ala Arg Asn Thr Met Ala Ala Cys Asp
290 295 300
Leu Arg Arg Gly Arg Tyr Leu Thr Val Ala Cys Ile Phe Arg Gly Lys
305 310 315 320
Met Ser Thr Lys Glu Val Asp Gln Gln Leu Leu Ser Val Gln Thr Arg
325 330 335
Asn Ser Ser Cys Phe Val Glu Trp Ile Pro Asn Asn Val Lys Val Ala
340 345 350
Val Cys Asp Ile Pro Pro Arg Gly Leu Ser Met Ala Ala Thr Phe Ile
355 360 365
Gly Asn Asn Thr Ala Ile Gln Glu Ile Phe Asn Arg Val Ser Glu His
370 375 380
Phe Ser Ala Met Phe Lys Arg Lys Ala Phe Val His Trp Tyr Thr Ser
385 390 395 400
Glu Gly Met Asp Ile Asn Glu Phe Gly Glu Ala Glu Asn Asn Ile His
405 410 415
Asp Leu Val Ser Glu Tyr Gln Gln Phe Gln Asp Ala Lys Ala Val Leu
420 425 430
Glu Glu Asp Glu Glu Val Thr Glu Glu Ala Glu Met Glu Pro Glu Asp
435 440 445
Lys Gly His
450
<210> 180
<211> 494
<212> PRT
<213> 智人
<400> 180
Met Phe Glu Ile Lys Lys Ile Cys Cys Ile Gly Ala Gly Tyr Val Gly
1 5 10 15
Gly Pro Thr Cys Ser Val Ile Ala His Met Cys Pro Glu Ile Arg Val
20 25 30
Thr Val Val Asp Val Asn Glu Ser Arg Ile Asn Ala Trp Asn Ser Pro
35 40 45
Thr Leu Pro Ile Tyr Glu Pro Gly Leu Lys Glu Val Val Glu Ser Cys
50 55 60
Arg Gly Lys Asn Leu Phe Phe Ser Thr Asn Ile Asp Asp Ala Ile Lys
65 70 75 80
Glu Ala Asp Leu Val Phe Ile Ser Val Asn Thr Pro Thr Lys Thr Tyr
85 90 95
Gly Met Gly Lys Gly Arg Ala Ala Asp Leu Lys Tyr Ile Glu Ala Cys
100 105 110
Ala Arg Arg Ile Val Gln Asn Ser Asn Gly Tyr Lys Ile Val Thr Glu
115 120 125
Lys Ser Thr Val Pro Val Arg Ala Ala Glu Ser Ile Arg Arg Ile Phe
130 135 140
Asp Ala Asn Thr Lys Pro Asn Leu Asn Leu Gln Val Leu Ser Asn Pro
145 150 155 160
Glu Phe Leu Ala Glu Gly Thr Ala Ile Lys Asp Leu Lys Asn Pro Asp
165 170 175
Arg Val Leu Ile Gly Gly Asp Glu Thr Pro Glu Gly Gln Arg Ala Val
180 185 190
Gln Ala Leu Cys Ala Val Tyr Glu His Trp Val Pro Arg Glu Lys Ile
195 200 205
Leu Thr Thr Asn Thr Trp Ser Ser Glu Leu Ser Lys Leu Ala Ala Asn
210 215 220
Ala Phe Leu Ala Gln Arg Ile Ser Ser Ile Asn Ser Ile Ser Ala Leu
225 230 235 240
Cys Glu Ala Thr Gly Ala Asp Val Glu Glu Val Ala Thr Ala Ile Gly
245 250 255
Met Asp Gln Arg Ile Gly Asn Lys Phe Leu Lys Ala Ser Val Gly Phe
260 265 270
Gly Gly Ser Cys Phe Gln Lys Asp Val Leu Asn Leu Val Tyr Leu Cys
275 280 285
Glu Ala Leu Asn Leu Pro Glu Val Ala Arg Tyr Trp Gln Gln Val Ile
290 295 300
Asp Met Asn Asp Tyr Gln Arg Arg Arg Phe Ala Ser Arg Ile Ile Asp
305 310 315 320
Ser Leu Phe Asn Thr Val Thr Asp Lys Lys Ile Ala Ile Leu Gly Phe
325 330 335
Ala Phe Lys Lys Asp Thr Gly Asp Thr Arg Glu Ser Ser Ser Ile Tyr
340 345 350
Ile Ser Lys Tyr Leu Met Asp Glu Gly Ala His Leu His Ile Tyr Asp
355 360 365
Pro Lys Val Pro Arg Glu Gln Ile Val Val Asp Leu Ser His Pro Gly
370 375 380
Val Ser Glu Asp Asp Gln Val Ser Arg Leu Val Thr Ile Ser Lys Asp
385 390 395 400
Pro Tyr Glu Ala Cys Asp Gly Ala His Ala Val Val Ile Cys Thr Glu
405 410 415
Trp Asp Met Phe Lys Glu Leu Asp Tyr Glu Arg Ile His Lys Lys Met
420 425 430
Leu Lys Pro Ala Phe Ile Phe Asp Gly Arg Arg Val Leu Asp Gly Leu
435 440 445
His Asn Glu Leu Gln Thr Ile Gly Phe Gln Ile Glu Thr Ile Gly Lys
450 455 460
Lys Val Ser Ser Lys Arg Ile Pro Tyr Ala Pro Ser Gly Glu Ile Pro
465 470 475 480
Lys Phe Ser Leu Gln Asp Pro Pro Asn Lys Lys Pro Lys Val
485 490
<210> 181
<211> 508
<212> PRT
<213> 智人
<400> 181
Met Ser Arg Phe Val Gln Asp Leu Ser Lys Ala Met Ser Gln Asp Gly
1 5 10 15
Ala Ser Gln Phe Gln Glu Val Ile Arg Gln Glu Leu Glu Leu Ser Val
20 25 30
Lys Lys Glu Leu Glu Lys Ile Leu Thr Thr Ala Ser Ser His Glu Phe
35 40 45
Glu His Thr Lys Lys Asp Leu Asp Gly Phe Arg Lys Leu Phe His Arg
50 55 60
Phe Leu Gln Glu Lys Gly Pro Ser Val Asp Trp Gly Lys Ile Gln Arg
65 70 75 80
Pro Pro Glu Asp Ser Ile Gln Pro Tyr Glu Lys Ile Lys Ala Arg Gly
85 90 95
Leu Pro Asp Asn Ile Ser Ser Val Leu Asn Lys Leu Val Val Val Lys
100 105 110
Leu Asn Gly Gly Leu Gly Thr Ser Met Gly Cys Lys Gly Pro Lys Ser
115 120 125
Leu Ile Gly Val Arg Asn Glu Asn Thr Phe Leu Asp Leu Thr Val Gln
130 135 140
Gln Ile Glu His Leu Asn Lys Thr Tyr Asn Thr Asp Val Pro Leu Val
145 150 155 160
Leu Met Asn Ser Phe Asn Thr Asp Glu Asp Thr Lys Lys Ile Leu Gln
165 170 175
Lys Tyr Asn His Cys Arg Val Lys Ile Tyr Thr Phe Asn Gln Ser Arg
180 185 190
Tyr Pro Arg Ile Asn Lys Glu Ser Leu Leu Pro Val Ala Lys Asp Val
195 200 205
Ser Tyr Ser Gly Glu Asn Thr Glu Ala Trp Tyr Pro Pro Gly His Gly
210 215 220
Asp Ile Tyr Ala Ser Phe Tyr Asn Ser Gly Leu Leu Asp Thr Phe Ile
225 230 235 240
Gly Glu Gly Lys Glu Tyr Ile Phe Val Ser Asn Ile Asp Asn Leu Gly
245 250 255
Ala Thr Val Asp Leu Tyr Ile Leu Asn His Leu Met Asn Pro Pro Asn
260 265 270
Gly Lys Arg Cys Glu Phe Val Met Glu Val Thr Asn Lys Thr Arg Ala
275 280 285
Asp Val Lys Gly Gly Thr Leu Thr Gln Tyr Glu Gly Lys Leu Arg Leu
290 295 300
Val Glu Ile Ala Gln Val Pro Lys Ala His Val Asp Glu Phe Lys Ser
305 310 315 320
Val Ser Lys Phe Lys Ile Phe Asn Thr Asn Asn Leu Trp Ile Ser Leu
325 330 335
Ala Ala Val Lys Arg Leu Gln Glu Gln Asn Ala Ile Asp Met Glu Ile
340 345 350
Ile Val Asn Ala Lys Thr Leu Asp Gly Gly Leu Asn Val Ile Gln Leu
355 360 365
Glu Thr Ala Val Gly Ala Ala Ile Lys Ser Phe Glu Asn Ser Leu Gly
370 375 380
Ile Asn Val Pro Arg Ser Arg Phe Leu Pro Val Lys Thr Thr Ser Asp
385 390 395 400
Leu Leu Leu Val Met Ser Asn Leu Tyr Ser Leu Asn Ala Gly Ser Leu
405 410 415
Thr Met Ser Glu Lys Arg Glu Phe Pro Thr Val Pro Leu Val Lys Leu
420 425 430
Gly Ser Ser Phe Thr Lys Val Gln Asp Tyr Leu Arg Arg Phe Glu Ser
435 440 445
Ile Pro Asp Met Leu Glu Leu Asp His Leu Thr Val Ser Gly Asp Val
450 455 460
Thr Phe Gly Lys Asn Val Ser Leu Lys Gly Thr Val Ile Ile Ile Ala
465 470 475 480
Asn His Gly Asp Arg Ile Asp Ile Pro Pro Gly Ala Val Leu Glu Asn
485 490 495
Lys Ile Val Ser Gly Asn Leu Arg Ile Leu Asp His
500 505
<210> 182
<211> 232
<212> PRT
<213> 智人
<400> 182
Met Asn Phe Leu Leu Ser Trp Val His Trp Ser Leu Ala Leu Leu Leu
1 5 10 15
Tyr Leu His His Ala Lys Trp Ser Gln Ala Ala Pro Met Ala Glu Gly
20 25 30
Gly Gly Gln Asn His His Glu Val Val Lys Phe Met Asp Val Tyr Gln
35 40 45
Arg Ser Tyr Cys His Pro Ile Glu Thr Leu Val Asp Ile Phe Gln Glu
50 55 60
Tyr Pro Asp Glu Ile Glu Tyr Ile Phe Lys Pro Ser Cys Val Pro Leu
65 70 75 80
Met Arg Cys Gly Gly Cys Cys Asn Asp Glu Gly Leu Glu Cys Val Pro
85 90 95
Thr Glu Glu Ser Asn Ile Thr Met Gln Ile Met Arg Ile Lys Pro His
100 105 110
Gln Gly Gln His Ile Gly Glu Met Ser Phe Leu Gln His Asn Lys Cys
115 120 125
Glu Cys Arg Pro Lys Lys Asp Arg Ala Arg Gln Glu Lys Lys Ser Val
130 135 140
Arg Gly Lys Gly Lys Gly Gln Lys Arg Lys Arg Lys Lys Ser Arg Tyr
145 150 155 160
Lys Ser Trp Ser Val Tyr Val Gly Ala Arg Cys Cys Leu Met Pro Trp
165 170 175
Ser Leu Pro Gly Pro His Pro Cys Gly Pro Cys Ser Glu Arg Arg Lys
180 185 190
His Leu Phe Val Gln Asp Pro Gln Thr Cys Lys Cys Ser Cys Lys Asn
195 200 205
Thr Asp Ser Arg Cys Lys Ala Arg Gln Leu Glu Leu Asn Glu Arg Thr
210 215 220
Cys Arg Cys Asp Lys Pro Arg Arg
225 230
<210> 183
<211> 827
<212> PRT
<213> 智人
<400> 183
Met Thr Lys Leu Ser Ala Gln Val Lys Gly Ser Leu Asn Ile Thr Thr
1 5 10 15
Pro Gly Leu Gln Ile Trp Arg Ile Glu Ala Met Gln Met Val Pro Val
20 25 30
Pro Ser Ser Thr Phe Gly Ser Phe Phe Asp Gly Asp Cys Tyr Ile Ile
35 40 45
Leu Ala Ile His Lys Thr Ala Ser Ser Leu Ser Tyr Asp Ile His Tyr
50 55 60
Trp Ile Gly Gln Asp Ser Ser Leu Asp Glu Gln Gly Ala Ala Ala Ile
65 70 75 80
Tyr Thr Thr Gln Met Asp Asp Phe Leu Lys Gly Arg Ala Val Gln His
85 90 95
Arg Glu Val Gln Gly Asn Glu Ser Glu Ala Phe Arg Gly Tyr Phe Lys
100 105 110
Gln Gly Leu Val Ile Arg Lys Gly Gly Val Ala Ser Gly Met Lys His
115 120 125
Val Glu Thr Asn Ser Tyr Asp Val Gln Arg Leu Leu His Val Lys Gly
130 135 140
Lys Arg Asn Val Val Ala Gly Glu Val Glu Met Ser Trp Lys Ser Phe
145 150 155 160
Asn Arg Gly Asp Val Phe Leu Leu Asp Leu Gly Lys Leu Ile Ile Gln
165 170 175
Trp Asn Gly Pro Glu Ser Thr Arg Met Glu Arg Leu Arg Gly Met Thr
180 185 190
Leu Ala Lys Glu Ile Arg Asp Gln Glu Arg Gly Gly Arg Thr Tyr Val
195 200 205
Gly Val Val Asp Gly Glu Asn Glu Leu Ala Ser Pro Lys Leu Met Glu
210 215 220
Val Met Asn His Val Leu Gly Lys Arg Arg Glu Leu Lys Ala Ala Val
225 230 235 240
Pro Asp Thr Val Val Glu Pro Ala Leu Lys Ala Ala Leu Lys Leu Tyr
245 250 255
His Val Ser Asp Ser Glu Gly Asn Leu Val Val Arg Glu Val Ala Thr
260 265 270
Arg Pro Leu Thr Gln Asp Leu Leu Ser His Glu Asp Cys Tyr Ile Leu
275 280 285
Asp Gln Gly Gly Leu Lys Ile Tyr Val Trp Lys Gly Lys Lys Ala Asn
290 295 300
Glu Gln Glu Lys Lys Gly Ala Met Ser His Ala Leu Asn Phe Ile Lys
305 310 315 320
Ala Lys Gln Tyr Pro Pro Ser Thr Gln Val Glu Val Gln Asn Asp Gly
325 330 335
Ala Glu Ser Ala Val Phe Gln Gln Leu Phe Gln Lys Trp Thr Ala Ser
340 345 350
Asn Arg Thr Ser Gly Leu Gly Lys Thr His Thr Val Gly Ser Val Ala
355 360 365
Lys Val Glu Gln Val Lys Phe Asp Ala Thr Ser Met His Val Lys Pro
370 375 380
Gln Val Ala Ala Gln Gln Lys Met Val Asp Asp Gly Ser Gly Glu Val
385 390 395 400
Gln Val Trp Arg Ile Glu Asn Leu Glu Leu Val Pro Val Asp Ser Lys
405 410 415
Trp Leu Gly His Phe Tyr Gly Gly Asp Cys Tyr Leu Leu Leu Tyr Thr
420 425 430
Tyr Leu Ile Gly Glu Lys Gln His Tyr Leu Leu Tyr Val Trp Gln Gly
435 440 445
Ser Gln Ala Ser Gln Asp Glu Ile Thr Ala Ser Ala Tyr Gln Ala Val
450 455 460
Ile Leu Asp Gln Lys Tyr Asn Gly Glu Pro Val Gln Ile Arg Val Pro
465 470 475 480
Met Gly Lys Glu Pro Pro His Leu Met Ser Ile Phe Lys Gly Arg Met
485 490 495
Val Val Tyr Gln Gly Gly Thr Ser Arg Thr Asn Asn Leu Glu Thr Gly
500 505 510
Pro Ser Thr Arg Leu Phe Gln Val Gln Gly Thr Gly Ala Asn Asn Thr
515 520 525
Lys Ala Phe Glu Val Pro Ala Arg Ala Asn Phe Leu Asn Ser Asn Asp
530 535 540
Val Phe Val Leu Lys Thr Gln Ser Cys Cys Tyr Leu Trp Cys Gly Lys
545 550 555 560
Gly Cys Ser Gly Asp Glu Arg Glu Met Ala Lys Met Val Ala Asp Thr
565 570 575
Ile Ser Arg Thr Glu Lys Gln Val Val Val Glu Gly Gln Glu Pro Ala
580 585 590
Asn Phe Trp Met Ala Leu Gly Gly Lys Ala Pro Tyr Ala Asn Thr Lys
595 600 605
Arg Leu Gln Glu Glu Asn Leu Val Ile Thr Pro Arg Leu Phe Glu Cys
610 615 620
Ser Asn Lys Thr Gly Arg Phe Leu Ala Thr Glu Ile Pro Asp Phe Asn
625 630 635 640
Gln Asp Asp Leu Glu Glu Asp Asp Val Phe Leu Leu Asp Val Trp Asp
645 650 655
Gln Val Phe Phe Trp Ile Gly Lys His Ala Asn Glu Glu Glu Lys Lys
660 665 670
Ala Ala Ala Thr Thr Ala Gln Glu Tyr Leu Lys Thr His Pro Ser Gly
675 680 685
Arg Asp Pro Glu Thr Pro Ile Ile Val Val Lys Gln Gly His Glu Pro
690 695 700
Pro Thr Phe Thr Gly Trp Phe Leu Ala Trp Asp Pro Phe Lys Trp Ser
705 710 715 720
Asn Thr Lys Ser Tyr Glu Asp Leu Lys Ala Glu Leu Gly Asn Ser Arg
725 730 735
Asp Trp Ser Gln Ile Thr Ala Glu Val Thr Ser Pro Lys Val Asp Val
740 745 750
Phe Asn Ala Asn Ser Asn Leu Ser Ser Gly Pro Leu Pro Ile Phe Pro
755 760 765
Leu Glu Gln Leu Val Asn Lys Pro Val Glu Glu Leu Pro Glu Gly Val
770 775 780
Asp Pro Ser Arg Lys Glu Glu His Leu Ser Ile Glu Asp Phe Thr Gln
785 790 795 800
Ala Phe Gly Met Thr Pro Ala Ala Phe Ser Ala Leu Pro Arg Trp Lys
805 810 815
Gln Gln Asn Leu Lys Lys Glu Lys Gly Leu Phe
820 825
<210> 184
<211> 466
<212> PRT
<213> 智人
<400> 184
Met Ser Thr Arg Ser Val Ser Ser Ser Ser Tyr Arg Arg Met Phe Gly
1 5 10 15
Gly Pro Gly Thr Ala Ser Arg Pro Ser Ser Ser Arg Ser Tyr Val Thr
20 25 30
Thr Ser Thr Arg Thr Tyr Ser Leu Gly Ser Ala Leu Arg Pro Ser Thr
35 40 45
Ser Arg Ser Leu Tyr Ala Ser Ser Pro Gly Gly Val Tyr Ala Thr Arg
50 55 60
Ser Ser Ala Val Arg Leu Arg Ser Ser Val Pro Gly Val Arg Leu Leu
65 70 75 80
Gln Asp Ser Val Asp Phe Ser Leu Ala Asp Ala Ile Asn Thr Glu Phe
85 90 95
Lys Asn Thr Arg Thr Asn Glu Lys Val Glu Leu Gln Glu Leu Asn Asp
100 105 110
Arg Phe Ala Asn Tyr Ile Asp Lys Val Arg Phe Leu Glu Gln Gln Asn
115 120 125
Lys Ile Leu Leu Ala Glu Leu Glu Gln Leu Lys Gly Gln Gly Lys Ser
130 135 140
Arg Leu Gly Asp Leu Tyr Glu Glu Glu Met Arg Glu Leu Arg Arg Gln
145 150 155 160
Val Asp Gln Leu Thr Asn Asp Lys Ala Arg Val Glu Val Glu Arg Asp
165 170 175
Asn Leu Ala Glu Asp Ile Met Arg Leu Arg Glu Lys Leu Gln Glu Glu
180 185 190
Met Leu Gln Arg Glu Glu Ala Glu Asn Thr Leu Gln Ser Phe Arg Gln
195 200 205
Asp Val Asp Asn Ala Ser Leu Ala Arg Leu Asp Leu Glu Arg Lys Val
210 215 220
Glu Ser Leu Gln Glu Glu Ile Ala Phe Leu Lys Lys Leu His Glu Glu
225 230 235 240
Glu Ile Gln Glu Leu Gln Ala Gln Ile Gln Glu Gln His Val Gln Ile
245 250 255
Asp Val Asp Val Ser Lys Pro Asp Leu Thr Ala Ala Leu Arg Asp Val
260 265 270
Arg Gln Gln Tyr Glu Ser Val Ala Ala Lys Asn Leu Gln Glu Ala Glu
275 280 285
Glu Trp Tyr Lys Ser Lys Phe Ala Asp Leu Ser Glu Ala Ala Asn Arg
290 295 300
Asn Asn Asp Ala Leu Arg Gln Ala Lys Gln Glu Ser Thr Glu Tyr Arg
305 310 315 320
Arg Gln Val Gln Ser Leu Thr Cys Glu Val Asp Ala Leu Lys Gly Thr
325 330 335
Asn Glu Ser Leu Glu Arg Gln Met Arg Glu Met Glu Glu Asn Phe Ala
340 345 350
Val Glu Ala Ala Asn Tyr Gln Asp Thr Ile Gly Arg Leu Gln Asp Glu
355 360 365
Ile Gln Asn Met Lys Glu Glu Met Ala Arg His Leu Arg Glu Tyr Gln
370 375 380
Asp Leu Leu Asn Val Lys Met Ala Leu Asp Ile Glu Ile Ala Thr Tyr
385 390 395 400
Arg Lys Leu Leu Glu Gly Glu Glu Ser Arg Ile Ser Leu Pro Leu Pro
405 410 415
Asn Phe Ser Ser Leu Asn Leu Arg Glu Thr Asn Leu Asp Ser Leu Pro
420 425 430
Leu Val Asp Thr His Ser Lys Arg Thr Leu Leu Ile Lys Thr Val Glu
435 440 445
Thr Arg Asp Gly Gln Val Ile Asn Glu Thr Ser Gln His His Asp Asp
450 455 460
Leu Glu
465
<210> 185
<211> 513
<212> PRT
<213> 智人
<400> 185
Met Thr Thr Gln Leu Pro Ala Tyr Val Ala Ile Leu Leu Phe Tyr Val
1 5 10 15
Ser Arg Ala Ser Cys Gln Asp Thr Phe Thr Ala Ala Val Tyr Glu His
20 25 30
Ala Ala Ile Leu Pro Asn Ala Thr Leu Thr Pro Val Ser Arg Glu Glu
35 40 45
Ala Leu Ala Leu Met Asn Arg Asn Leu Asp Ile Leu Glu Gly Ala Ile
50 55 60
Thr Ser Ala Ala Asp Gln Gly Ala His Ile Ile Val Thr Pro Glu Asp
65 70 75 80
Ala Ile Tyr Gly Trp Asn Phe Asn Arg Asp Ser Leu Tyr Pro Tyr Leu
85 90 95
Glu Asp Ile Pro Asp Pro Glu Val Asn Trp Ile Pro Cys Asn Asn Arg
100 105 110
Asn Arg Phe Gly Gln Thr Pro Val Gln Glu Arg Leu Ser Cys Leu Ala
115 120 125
Lys Asn Asn Ser Ile Tyr Val Val Ala Asn Ile Gly Asp Lys Lys Pro
130 135 140
Cys Asp Thr Ser Asp Pro Gln Cys Pro Pro Asp Gly Arg Tyr Gln Tyr
145 150 155 160
Asn Thr Asp Val Val Phe Asp Ser Gln Gly Lys Leu Val Ala Arg Tyr
165 170 175
His Lys Gln Asn Leu Phe Met Gly Glu Asn Gln Phe Asn Val Pro Lys
180 185 190
Glu Pro Glu Ile Val Thr Phe Asn Thr Thr Phe Gly Ser Phe Gly Ile
195 200 205
Phe Thr Cys Phe Asp Ile Leu Phe His Asp Pro Ala Val Thr Leu Val
210 215 220
Lys Asp Phe His Val Asp Thr Ile Val Phe Pro Thr Ala Trp Met Asn
225 230 235 240
Val Leu Pro His Leu Ser Ala Val Glu Phe His Ser Ala Trp Ala Met
245 250 255
Gly Met Arg Val Asn Phe Leu Ala Ser Asn Ile His Tyr Pro Ser Lys
260 265 270
Lys Met Thr Gly Ser Gly Ile Tyr Ala Pro Asn Ser Ser Arg Ala Phe
275 280 285
His Tyr Asp Met Lys Thr Glu Glu Gly Lys Leu Leu Leu Ser Gln Leu
290 295 300
Asp Ser His Pro Ser His Ser Ala Val Val Asn Trp Thr Ser Tyr Ala
305 310 315 320
Ser Ser Ile Glu Ala Leu Ser Ser Gly Asn Lys Glu Phe Lys Gly Thr
325 330 335
Val Phe Phe Asp Glu Phe Thr Phe Val Lys Leu Thr Gly Val Ala Gly
340 345 350
Asn Tyr Thr Val Cys Gln Lys Asp Leu Cys Cys His Leu Ser Tyr Lys
355 360 365
Met Ser Glu Asn Ile Pro Asn Glu Val Tyr Ala Leu Gly Ala Phe Asp
370 375 380
Gly Leu His Thr Val Glu Gly Arg Tyr Tyr Leu Gln Ile Cys Thr Leu
385 390 395 400
Leu Lys Cys Lys Thr Thr Asn Leu Asn Thr Cys Gly Asp Ser Ala Glu
405 410 415
Thr Ala Ser Thr Arg Phe Glu Met Phe Ser Leu Ser Gly Thr Phe Gly
420 425 430
Thr Gln Tyr Val Phe Pro Glu Val Leu Leu Ser Glu Asn Gln Leu Ala
435 440 445
Pro Gly Glu Phe Gln Val Ser Thr Asp Gly Arg Leu Phe Ser Leu Lys
450 455 460
Pro Thr Ser Gly Pro Val Leu Thr Val Thr Leu Phe Gly Arg Leu Tyr
465 470 475 480
Glu Lys Asp Trp Ala Ser Asn Ala Ser Ser Gly Leu Thr Ala Gln Ala
485 490 495
Arg Ile Ile Met Leu Ile Val Ile Ala Pro Ile Val Cys Ser Leu Ser
500 505 510
Trp
<210> 186
<211> 245
<212> PRT
<213> 智人
<400> 186
Met Asp Lys Asn Glu Leu Val Gln Lys Ala Lys Leu Ala Glu Gln Ala
1 5 10 15
Glu Arg Tyr Asp Asp Met Ala Ala Cys Met Lys Ser Val Thr Glu Gln
20 25 30
Gly Ala Glu Leu Ser Asn Glu Glu Arg Asn Leu Leu Ser Val Ala Tyr
35 40 45
Lys Asn Val Val Gly Ala Arg Arg Ser Ser Trp Arg Val Val Ser Ser
50 55 60
Ile Glu Gln Lys Thr Glu Gly Ala Glu Lys Lys Gln Gln Met Ala Arg
65 70 75 80
Glu Tyr Arg Glu Lys Ile Glu Thr Glu Leu Arg Asp Ile Cys Asn Asp
85 90 95
Val Leu Ser Leu Leu Glu Lys Phe Leu Ile Pro Asn Ala Ser Gln Ala
100 105 110
Glu Ser Lys Val Phe Tyr Leu Lys Met Lys Gly Asp Tyr Tyr Arg Tyr
115 120 125
Leu Ala Glu Val Ala Ala Gly Asp Asp Lys Lys Gly Ile Val Asp Gln
130 135 140
Ser Gln Gln Ala Tyr Gln Glu Ala Phe Glu Ile Ser Lys Lys Glu Met
145 150 155 160
Gln Pro Thr His Pro Ile Arg Leu Gly Leu Ala Leu Asn Phe Ser Val
165 170 175
Phe Tyr Tyr Glu Ile Leu Asn Ser Pro Glu Lys Ala Cys Ser Leu Ala
180 185 190
Lys Thr Ala Phe Asp Glu Ala Ile Ala Glu Leu Asp Thr Leu Ser Glu
195 200 205
Glu Ser Tyr Lys Asp Ser Thr Leu Ile Met Gln Leu Leu Arg Asp Asn
210 215 220
Leu Thr Leu Trp Thr Ser Asp Thr Gln Gly Asp Glu Ala Glu Ala Gly
225 230 235 240
Glu Gly Gly Glu Asn
245
<210> 187
<211> 352
<212> PRT
<213> 智人
<400> 187
Met Asp Tyr Gln Val Ser Ser Pro Ile Tyr Asp Ile Asn Tyr Tyr Thr
1 5 10 15
Ser Glu Pro Cys Gln Lys Ile Asn Val Lys Gln Ile Ala Ala Arg Leu
20 25 30
Leu Pro Pro Leu Tyr Ser Leu Val Phe Ile Phe Gly Phe Val Gly Asn
35 40 45
Met Leu Val Ile Leu Ile Leu Ile Asn Cys Lys Arg Leu Lys Ser Met
50 55 60
Thr Asp Ile Tyr Leu Leu Asn Leu Ala Ile Ser Asp Leu Phe Phe Leu
65 70 75 80
Leu Thr Val Pro Phe Trp Ala His Tyr Ala Ala Ala Gln Trp Asp Phe
85 90 95
Gly Asn Thr Met Cys Gln Leu Leu Thr Gly Leu Tyr Phe Ile Gly Phe
100 105 110
Phe Ser Gly Ile Phe Phe Ile Ile Leu Leu Thr Ile Asp Arg Tyr Leu
115 120 125
Ala Val Val His Ala Val Phe Ala Leu Lys Ala Arg Thr Val Thr Phe
130 135 140
Gly Val Val Thr Ser Val Ile Thr Trp Val Val Ala Val Phe Ala Ser
145 150 155 160
Leu Pro Gly Ile Ile Phe Thr Arg Ser Gln Lys Glu Gly Leu His Tyr
165 170 175
Thr Cys Ser Ser His Phe Pro Tyr Ser Gln Tyr Gln Phe Trp Lys Asn
180 185 190
Phe Gln Thr Leu Lys Ile Val Ile Leu Gly Leu Val Leu Pro Leu Leu
195 200 205
Val Met Val Ile Cys Tyr Ser Gly Ile Leu Lys Thr Leu Leu Arg Cys
210 215 220
Arg Asn Glu Lys Lys Arg His Arg Ala Val Arg Leu Ile Phe Thr Ile
225 230 235 240
Met Ile Val Tyr Phe Leu Phe Trp Ala Pro Tyr Asn Ile Val Leu Leu
245 250 255
Leu Asn Thr Phe Gln Glu Phe Phe Gly Leu Asn Asn Cys Ser Ser Ser
260 265 270
Asn Arg Leu Asp Gln Ala Met Gln Val Thr Glu Thr Leu Gly Met Thr
275 280 285
His Cys Cys Ile Asn Pro Ile Ile Tyr Ala Phe Val Gly Glu Lys Phe
290 295 300
Arg Asn Tyr Leu Leu Val Phe Phe Gln Lys His Ile Ala Lys Arg Phe
305 310 315 320
Cys Lys Cys Cys Ser Ile Phe Gln Gln Glu Ala Pro Glu Arg Ala Ser
325 330 335
Ser Val Tyr Thr Arg Ser Thr Gly Glu Gln Glu Ile Ser Val Gly Leu
340 345 350
<210> 188
<211> 467
<212> PRT
<213> 智人
<400> 188
Met Arg Pro Gln Glu Leu Pro Arg Leu Ala Phe Pro Leu Leu Leu Leu
1 5 10 15
Leu Leu Leu Leu Leu Pro Pro Pro Pro Cys Pro Ala His Ser Ala Thr
20 25 30
Arg Phe Asp Pro Thr Trp Glu Ser Leu Asp Ala Arg Gln Leu Pro Ala
35 40 45
Trp Phe Asp Gln Ala Lys Phe Gly Ile Phe Ile His Trp Gly Val Phe
50 55 60
Ser Val Pro Ser Phe Gly Ser Glu Trp Phe Trp Trp Tyr Trp Gln Lys
65 70 75 80
Glu Lys Ile Pro Lys Tyr Val Glu Phe Met Lys Asp Asn Tyr Pro Pro
85 90 95
Ser Phe Lys Tyr Glu Asp Phe Gly Pro Leu Phe Thr Ala Lys Phe Phe
100 105 110
Asn Ala Asn Gln Trp Ala Asp Ile Phe Gln Ala Ser Gly Ala Lys Tyr
115 120 125
Ile Val Leu Thr Ser Lys His His Glu Gly Phe Thr Leu Trp Gly Ser
130 135 140
Glu Tyr Ser Trp Asn Trp Asn Ala Ile Asp Glu Gly Pro Lys Arg Asp
145 150 155 160
Ile Val Lys Glu Leu Glu Val Ala Ile Arg Asn Arg Thr Asp Leu Arg
165 170 175
Phe Gly Leu Tyr Tyr Ser Leu Phe Glu Trp Phe His Pro Leu Phe Leu
180 185 190
Glu Asp Glu Ser Ser Ser Phe His Lys Arg Gln Phe Pro Val Ser Lys
195 200 205
Thr Leu Pro Glu Leu Tyr Glu Leu Val Asn Asn Tyr Gln Pro Glu Val
210 215 220
Leu Trp Ser Asp Gly Asp Gly Gly Ala Pro Asp Gln Tyr Trp Asn Ser
225 230 235 240
Thr Gly Phe Leu Ala Trp Leu Tyr Asn Glu Ser Pro Val Arg Gly Thr
245 250 255
Val Val Thr Asn Asp Arg Trp Gly Ala Gly Ser Ile Cys Lys His Gly
260 265 270
Gly Phe Tyr Thr Cys Ser Asp Arg Tyr Asn Pro Gly His Leu Leu Pro
275 280 285
His Lys Trp Glu Asn Cys Met Thr Ile Asp Lys Leu Ser Trp Gly Tyr
290 295 300
Arg Arg Glu Ala Gly Ile Ser Asp Tyr Leu Thr Ile Glu Glu Leu Val
305 310 315 320
Lys Gln Leu Val Glu Thr Val Ser Cys Gly Gly Asn Leu Leu Met Asn
325 330 335
Ile Gly Pro Thr Leu Asp Gly Thr Ile Ser Val Val Phe Glu Glu Arg
340 345 350
Leu Arg Gln Met Gly Ser Trp Leu Lys Val Asn Gly Glu Ala Ile Tyr
355 360 365
Glu Thr His Thr Trp Arg Ser Gln Asn Asp Thr Val Thr Pro Asp Val
370 375 380
Trp Tyr Thr Ser Lys Pro Lys Glu Lys Leu Val Tyr Ala Ile Phe Leu
385 390 395 400
Lys Trp Pro Thr Ser Gly Gln Leu Phe Leu Gly His Pro Lys Ala Ile
405 410 415
Leu Gly Ala Thr Glu Val Lys Leu Leu Gly His Gly Gln Pro Leu Asn
420 425 430
Trp Ile Ser Leu Glu Gln Asn Gly Ile Met Val Glu Leu Pro Gln Leu
435 440 445
Thr Ile His Gln Met Pro Cys Lys Trp Gly Trp Ala Leu Ala Leu Thr
450 455 460
Asn Val Ile
465

Claims (10)

1.一种以大于70％的灵敏度或大于70％的选择性检测受试者结肠的腺瘤或息肉的存在的方法；所述方法包括以下步骤：
(a)从受试者获得血液样品；
(b)裂解所述血液样品中的蛋白质以提供包含肽的样品；
(c)分析所述样品中至少十种肽的存在；
(d)将分析所述样品的结果与对照参考值进行比较，从而以大于70％的灵敏度或大于70％的选择性确定存在结肠的腺瘤或息肉的正或负得分。
2.一种治疗受试者的结肠的腺瘤或息肉的方法，该方法包括：
(a)执行权利要求1所述的方法以得到具有存在腺瘤或息肉的正得分的受试者；以及
(b)进行用于去除所述受试者的腺瘤或息肉组织的程序。
3.一种检测受试者的结肠的腺瘤或息肉的存在与否的方法，其中所述受试者没有结肠的腺瘤或息肉的症状或家族史，所述方法包括以下步骤：
(a)从所述受试者获得生物样品；
(b)对所述生物样品进行关于一种或多种蛋白质和/或肽的存在和量的分析；
(c)将来自所述生物样品的一种或多种蛋白质和/或肽的存在和量与对照参考值进行比较；以及
(d)将一种或多种蛋白质和/或肽的存在和量与所述受试者的腺瘤或息肉状态相关联。
4.一种检测在结肠镜检查得到阴性结果的受试者中结肠的腺瘤或息肉的存在与否的方法，所述方法包括以下步骤：
(a)从基于结肠镜检查具有腺瘤或息肉的阴性诊断的受试者获得生物样品；
(b)对所述生物样品进行关于一种或多种蛋白质和/或肽的存在和量的分析；
(c)将来自所述生物样品的一种或多种蛋白质和/或肽的存在和量与对照参考值进行比较；以及
(d)将一种或多种蛋白质和/或肽的存在和量与所述受试者的腺瘤或息肉状态相关联。
5.一种检测先前治疗结肠的腺瘤或息肉的受试者中结肠的腺瘤或息肉的复发或不存在的方法，该方法包括以下步骤：
(a)从先前治疗结肠的腺瘤或息肉的受试者获得生物样品；
(b)对所述生物样品进行关于一种或多种蛋白质和/或肽的存在和量的分析；
(c)将来自所述生物样品的一种或多种蛋白质和/或肽的存在和量与对照参考值进行比较；以及
(d)将一种或多种蛋白质和/或肽的存在和量与所述受试者的腺瘤或息肉状态相关联。
6.一种针对诊断应用的蛋白质和/或肽检测方法，该方法包括以下步骤：
(a)从受试者获得生物样品；
(b)对所述生物样品进行关于一种或多种蛋白质和/或肽的存在和量的分析；
(c)将来自所述生物样品的一种或多种蛋白质和/或肽的存在和量与对照参考值进行比较；以及
(d)将一种或多种蛋白质和/或肽的存在和量与所述受试者的诊断相关联；
其中所述分析检测下组中的一种或多种的存在和量：
i)选自SCDC26(CD26)、CEA分子5(CEACAM5)、CA195(CCR5)、CA19-9、M2PK(PKM2)、TIMP1、P-选择蛋白(SELPLG)、VEGFA、HcGB(CGB)、绒毛蛋白、TATI(SPINK1)、A-L-岩藻糖苷酶(FUCA2)、ANXA5、GAPDH、PKM2、ANXA4、GARS、RRBP1、KRT8、SYNCRIP、S100A9、ANXA3、CAPG、HNRNPF、PPA1、NME1、PSME3、AHCY、TPT1、HSPB1和RPSA、和/或图9中的蛋白质，以及它们的组合的一种或多种蛋白质；
ii)SCDC26(CD26)、CEA分子5(CEACAM5)、CA195(CCR5)、CA19-9、M2PK(PKM2)、TIMP1、P-选择蛋白(SELPLG)、VEGFA、HcGB(CGB)、绒毛蛋白、TATI(SPINK1)、A-L-岩藻糖苷酶(FUCA2)和ANXA5、GAPDH、PKM2、ANXA4、GARS、RRBP1、KRT8、SYNCRIP、S100A9、ANXA3、CAPG、HNRNPF、PPA1、NME1、PSME3、AHCY、TPT1、HSPB1和RPSA、和/或图9中的蛋白质，以及它们的组合的一种或多种肽片段；
iii)与SCDC26(CD26)、CEA分子5(CEACAM5)、CA195(CCR5)、CA19-9、M2PK(PKM2)、TIMP1、P-选择蛋白(SELPLG)、VEGFA、HcGB(CGB)、绒毛蛋白、TATI(SPINK1)、A-L-岩藻糖苷酶(FUCA2)、ANXA5、GAPDH、PKM2、ANXA4、GARS、RRBP1、KRT8、SYNCRIP、S100A9、ANXA3、CAPG、HNRNPF、PPA1、NME1、PSME3、AHCY、TPT1、HSPB1和RPSA、和/或图9中的蛋白质，以及它们的组合具有序列同源性的一种或多种肽，其中所述序列同源性选自大于75％、大于80％、大于85％、大于90％、大于95％及大于99％；
iv)SCDC26(CD26)、CEA分子5(CEACAM5)、CA195(CCR5)、CA19-9、M2PK(PKM2)、TIMP1、P-选择蛋白(SELPLG)、VEGFA、HcGB(CGB)、绒毛蛋白、TATI(SPINK1)、A-L-岩藻糖苷酶(FUCA2)和ANXA5、GAPDH、PKM2、ANXA4、GARS、RRBP1、KRT8、SYNCRIP、S100A9、ANXA3、CAPG、HNRNPF、PPA1、NME1、PSME3、AHCY、TPT1、HSPB1和RPSA、和/或图9中的蛋白质，以及它们的组合的一种或多种结合配偶体；以及
v)从中得到图7或图8中的一个或多个中性质量簇的蛋白质或肽。
7.一种用于诊断、预测、预后和/或监测受试者的结肠疾病的方法，该方法包括：测量来自所述受试者的生物样品中选自下组的至少一种生物标志物：ACTB、ACTH、ANGT、SAHH、ALDR、AKT1、ALBU、AL1A1、AL1B1、ALDOA、AMY2B、ANXA1、ANXA3、ANXA4、ANXA5、APC、APOA1、APOC1、APOH、GDIR1、ATPB、BANK1、MIC1、CA195、CO3、CO9、CAH1、CAH2、CALR、CAPG、CD24、CD63、CDD、CEAM3、CEAM5、CEAM6、CGHB、CH3L1、KCRB、CLC4D、CLUS、CNN1、COR1C、CRP、CSF1、CTNB1、CATD、CATS、CATZ、CUL1、SYDC、DEF1、DEF3、DESM、DPP4、DPYL2、DYHC1、ECH1、EF2、IF4A3、ENOA、EZRI、NIBL2、SEPR、FBX4、FIBB、FIBG、FHL1、FLNA、FRMD3、FRIH、FRIL、FUCO、GBRA1、G3P、SYG、GDF15、GELS、GSTP1、HABP2、HGF、1A68、HMGB1、ROA1、ROA2、HNRPF、HPT、HS90B、ENPL、GRP75、HSPB1、CH60、SIAL、IFT74、IGF1、IGHA2、IL2RB、IL8、IL9、RASK、K1C19、K2C8、LAMA2、LEG3、LMNB1、MARE1、MCM4、MIF、MMP7、MMP9、CD20、MYL6、MYL9、NDKA、NNMT、A1AG1、PCKGM、PDIA3、PDIA6、PDXK、PEBP1、PIPNA、KPYM、UROK、IPYR、PRDX1、KPCD1、PRL、TMG4、PSME3、PTEN、FAK1、FAK2、RBX1、REG4、RHOA、RHOB、RHOC、RSSA、RRBP1、S10AB、S10AC、S10A8、S109、SAA1、SAA2、SEGN、SDCG3、DHSA、SBP1、SELPL、SEP9、A1AT、AACT、ILEU、SPB6、SF3B3、SKP1、ADT2、ISK1、SPON2、OSTP、SRC、STK11、HNRPQ、TAL1、TRFE、TSP1、TIMP1、TKT、TSG6、TR10B、TNF6B、P53、TPM2、TCTP、TRAP1、THTR、TBB1、UGDH、UGPA、VEGFA、VILI、VIME、VNN1、1433Z、CCR5、FUCO及其组合。
8.一种用于诊断、预测、预后和/或监测受试者的结肠疾病的方法，该方法包括：测量来自所述受试者的生物样品中选自SPB6、FRIL、P53、1A68、ENOA、TKT及其组合的至少一种生物标志物。
9.一种用于诊断、预测、预后和/或监测受试者的结肠疾病的方法，该方法包括：测量来自所述受试者的生物样品中选自SPB6、FRIL、P53、1A68、ENOA、TKT、TSG6、TPM2、ADT2、FHL1、CCR5、CEAM5、SPON2、1A68、RBX1、COR1C、VIME、PSME3及其组合的至少一种生物标志物。
10.一种用于诊断、预测、预后和/或监测受试者的结肠疾病的方法，该方法包括：测量来自所述受试者的生物样品中选自SPB6、FRIL、P53、1A68、ENOA、TKT、TSG6、TPM2、ADT2、FHL1、CCR5、CEAM5、SPON2、1A68、RBX1、COR1C、VIME、PSME3、MIC1、STK11、IPYR、SBP1、PEBP1、CATD、HPT、ANXA5、ALDOA、LAMA2、CATZ、ACTB、AACT及其组合的至少一种生物标志物。
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