CN112638947B - 用于治疗实体瘤的嵌合抗原受体细胞 - Google Patents

用于治疗实体瘤的嵌合抗原受体细胞 Download PDF

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CN112638947B
CN112638947B CN201980055593.2A CN201980055593A CN112638947B CN 112638947 B CN112638947 B CN 112638947B CN 201980055593 A CN201980055593 A CN 201980055593A CN 112638947 B CN112638947 B CN 112638947B
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肖磊
曹志远
王文升
蒲程飞
孙赫
毛丽
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Stacey Biotechnology Inc
Shanghai Sidansai Biotechnology Co ltd
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Abstract

本文描述的组合物和方法针对使用CAR T疗法治疗实体瘤。所述组合物包含CAR，所述CAR包含结合siglec蛋白的细胞外结构域或结合肽激素亲吻素的受体。

Description

用于治疗实体瘤的嵌合抗原受体细胞
相关申请的交叉引用
本申请要求2018年8月30日提交的美国临时专利申请62/725,025、2018年9月13日提交的美国临时专利申请62/731,079、2018年11月1日提交的美国临时专利申请62/754,175、2019年2月19日提交的美国临时专利申请62/807,482、2019年5月3日提交的美国临时专利申请62/842,936、以及2019年5月16日提交的美国临时专利申请62/848,984的权益，因此所述美国临时专利申请以引用的方式整体并入。
序列表信息
2019年8月29日左右创建的标题为“SDS1.0053PCT 8-29-2019_ST25.txt”的计算机可读文本文件，文件大小为约533KB，包含本申请的序列表，因此以引用的方式整体并入。
技术领域
本公开涉及修饰的细胞和用途，具体地说，涉及使用嵌合抗原受体(CAR)细胞治疗癌症的组合物和方法。
背景技术
现有的大多数癌症治疗方案包括外科手术、放射疗法、化学疗法、靶向疗法和免疫疗法。现有方案的缺点包括对晚期患者的治疗效果不佳、存在副作用、患者的生活质量较差。例如，肾癌的治疗包括切除、靶向疗法(抗VEGF和mTOR抑制剂等)和免疫疗法(IL-2、PD1抗体等)。胰腺癌的治疗包括手术切除、放射疗法和化学疗法。尿路上皮癌的治疗包括手术切除、放化疗、靶向疗法和免疫疗法。乳腺癌的治疗包括手术切除、放化疗、靶向疗法和免疫疗法。卵巢癌的治疗包括手术切除、放射疗法、化学疗法和靶向疗法。前列腺癌的治疗包括手术切除、放化疗、靶向疗法和免疫疗法。食管癌的治疗包括手术切除、放射疗法和化学疗法。结肠直肠癌的治疗包括手术切除、放射疗法、化学疗法和靶向疗法。子宫内膜癌的治疗包括手术切除、放射疗法、化学疗法和靶向疗法。
发明内容
实施方案涉及以下发现：与正常组织上的表达相比，某些抗原在肿瘤细胞上的表达相对较低。此外，在正常组织上表达时，某些其他抗原在特定组织(例如，一群细胞或器官)中特异性表达，并且杀死这些组织上的正常细胞不会对患者造成危及生命的事件(例如，并发症)。非必需组织的实例包括诸如前列腺、乳腺这样的器官、或黑色素细胞。因此，本公开的实施方案涉及嵌合抗原受体(CAR)，所述嵌合抗原受体包括结合这些抗原中的至少一种的细胞外结构域，并且涉及使用包括CAR的细胞来治疗癌症。
实施方案涉及使用CAR细胞治疗癌症的组合物和方法。实施方案涉及编码CAR的分离的核酸序列，其中CAR包括细胞外结构域、跨膜结构域和细胞内结构域，其中CAR的细胞外结构域结合实体瘤的抗原。抗原可以包括SIGLEC15、SLC6A3、KISS1R、QRFPR、GPR119、CLDN6、UPK2、ADAM 12、SLC45A3、ACPP、MUC21、MUC16、MS4A12、ALPP、SLC2A14、GS1-259H13.2、ERVFRD-1、ADGRG2、ECEL1、CHRNA2、GP2或PSG9。
本发明内容既不旨在标识所要求保护的主题的关键特征或必要特征，也不旨在用于限制所要求保护的主题的范围。
附图说明
参照附图对具体实施方式进行描述。在不同附图中使用相同的参考号指示相似或相同的项目。
图1为示出CAR结构的实例的示意图。
图2示出表达CAR的T细胞的流式细胞分析。
图3示出抗SIGLEC15 CAR杀伤测定的结果。
图4和图5示出抗SIGLEC15 CAR细胞因子释放测定的结果。
图6示出抗KISSR CAR杀伤测定的结果。
图7示出抗KISSR CAR细胞因子释放测定的结果。
图8、图9和图10示出ACPP抗体的流式细胞术测定。
图11示出前列腺癌石蜡切片的免疫荧光染色。
图12示出表达ACPP的293T细胞。
图13示出表达ACPP CAR的T细胞的流式细胞测定。
图14示出共培养测定的结果。
图15示出响应于ACPP的抗ACPP CAR T细胞的IFN-γ释放。
图16示出T细胞上的抗ACPP CAR的CAR表达可以通过检测人CAR抗体来测量。
图17示出抗ACPP CAR T细胞的细胞因子释放测定。
图18和图19示出不同条件下的CD137表达。
图20示出ELISA测定后小鼠血清中针对UPK2-His的抗体效价。
图21示出基于噬菌体ELISA分析8种噬菌体展示抗体与UPK2-His的结合。
图22示出重组单克隆抗体与重组UPK2-His结合的ELISA分析。
图23示出重组抗UPK2 mAb的特异性的ELISA分析。
图24示出结合分子的示例性结构。
图25示出标志物及其用途的表格。
图26示出CAR的示例性结构。
具体实施方式
除非另外定义，否则本文所用的所有技术术语和科学术语具有与本公开所属领域中的普通技术人员所通常理解的相同的含义。尽管可在本公开的实践或测试中使用与本文描述的那些方法和材料类似或等效的任何方法和材料，但还是描述了优选的方法和材料。为了本公开的目的，以下术语定义如下。
本文使用冠词“一个/种(a/an)”是指一个或多于一个(即，至少一个)物品的语法对象。举例来说，“一种要素”意指一种要素或多于一种要素。
“大约”意指数量、水平、值、数目、频率、百分比、尺寸、大小、量、重量或长度相对于参考数量、水平、值、数目、频率、百分比、尺寸、大小、量、重量或长度变化多达20％、15％、10％、9％、8％、7％、6％、5％、4％、3％、2％或1％。
如本文所用，术语“激活”是指已被充分刺激以诱导可检测的细胞增殖的细胞状态。激活也可以与诱导的细胞因子产生和可检测的效应子功能相关。术语“激活的T细胞”尤其是指正在进行细胞分裂的T细胞。
术语“抗体”的使用范围最广，是指单克隆抗体(包括全长单克隆抗体)、多克隆抗体、多特异性抗体(例如，双特异性抗体)和抗体片段，只要它们表现出所需的生物学活性或功能即可。本公开中的抗体可以以各种形式存在，包括例如多克隆抗体、单克隆抗体、Fv、Fab和F(ab)2，以及单链抗体和人源化抗体(Harlow等人,1999,In:Using Antibodies:ALaboratory Manual,Cold Spring Harbor Laboratory Press,NY；Harlow等人,1989,In:Antibodies:A Laboratory Manual,Cold Spring Harbor,New York；Houston等人,1988,Proc.Natl.Acad.Sci.USA 85:5879-5883；Bird等人,1988,Science 242:423-426)。
术语“抗体片段”是指全长抗体的一部分，例如，抗体的抗原结合区或可变区。抗体片段的其他实例包括Fab、Fab’、F(ab’)2和Fv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特异性抗体。术语“Fv”是指包含完整抗原识别和抗原结合位点的最小抗体片段。该片段由紧密、非共价缔合的一个重链可变区结构域和一个轻链可变区结构域的二聚体组成。通过这两个结构域的折叠，产生了六个高变环(3个环来自H链，3个环来自L链)，其贡献了用于抗原结合的氨基酸残基并赋予了对抗体的抗原结合特异性。然而，即使单个可变结构域(或仅包含对抗原具有特异性的三个互补决定区(CDR)的Fv的一半)也具有识别和结合抗原的能力，尽管其亲和力低于整个结合位点(二聚体)。
如本文所用的“抗体重链”是指以其天然存在的构型存在于所有抗体分子中的两种类型多肽链中的较大者。如本文所用的“抗体轻链”是指以其天然存在的构型存在于所有抗体分子中的两种类型多肽链中的较小者。κ和λ轻链是指两种主要的抗体轻链同种型。术语“合成抗体”是指使用重组DNA技术生成的抗体，诸如例如由噬菌体表达的抗体。所述术语还包括通过合成编码抗体的DNA分子和表达DNA分子以获得抗体或获得编码抗体的氨基酸而生成的抗体。使用本领域可用和众所周知的技术来获得合成DNA。
术语“抗原”是指引起免疫应答的分子，其可涉及抗体产生或特异性免疫能力细胞的激活或两者。抗原包括任何大分子，所述大分子包括所有蛋白质或肽，或衍生自重组或基因组DNA的分子。例如，包含编码引发免疫应答的蛋白质或肽的核苷酸序列或部分核苷酸序列的DNA，因此编码如本文所用的术语“抗原”。抗原不必仅由基因的全长核苷酸序列编码。抗原可以从生物样品中生成、合成或衍生自生物样品，所述生物样品包括组织样品、肿瘤样品、细胞或生物流体。
如本文所用，术语“抗肿瘤作用”是指与肿瘤体积减小、肿瘤细胞数减少、转移数减少、肿瘤细胞增殖减少、肿瘤细胞存活减少、具有肿瘤细胞的受试者的预期寿命增加或与癌性病状相关的各种生理症状改善相关的生物作用。也可以通过肽、多核苷酸、细胞和抗体首先在预防肿瘤发生方面的能力来表现出“抗肿瘤作用”。
术语“自体抗原”是指被免疫系统误认为是外来的抗原。自体抗原包括细胞蛋白、磷蛋白、细胞表面蛋白、细胞脂质、核酸、糖蛋白，包括细胞表面受体。
术语“自体的”用于描述衍生自受试者的材料，其随后被重新引入同一受试者中。
术语“同种异体的”用于描述衍生自相同物种的不同受试者的移植物。作为实例，供体受试者可以是相关或不相关的或受体受试者，但是供体受试者具有与受体受试者相似的免疫系统标志物。
术语“异种的”用于描述衍生自不同物种的受试者的移植物。作为实例，供体受试者与受体受试者来自不同的物种，并且供体受试者和受体受试者可以是遗传学和免疫学上不相容的。
术语“癌症”是指特征在于异常细胞快速且不受控制生长的疾病。癌细胞可以局部扩散，或通过血流和淋巴系统扩散至身体的其他部位。各种癌症的实例包括乳腺癌、前列腺癌、卵巢癌、子宫颈癌、皮肤癌、胰腺癌、结肠直肠癌、肾癌、肝癌、脑癌、淋巴瘤、白血病、肺癌等。
可以治疗的癌症包括未血管化或尚未充分血管化的肿瘤、以及血管化肿瘤。癌症可以包括非实体瘤(诸如血液肿瘤，例如白血病和淋巴瘤)，或可以包括实体瘤。待用本公开的CAR治疗的癌症类型包括但不限于癌瘤、母细胞瘤和肉瘤，以及某些白血病或淋巴样恶性肿瘤、良性和恶性肿瘤及恶性肿瘤，例如肉瘤、癌瘤和黑色素瘤。成人肿瘤/癌症和儿科肿瘤/癌症也包括在内。
血液癌症是血液或骨髓的癌症。血液学(或血源性)癌症的实例包括白血病，包括急性白血病(诸如急性淋巴细胞白血病、急性骨髓性白血病、急性骨髓性白血病和成髓细胞性、早幼粒细胞性、髓单核细胞性、单核细胞性和红血球性白血病)、慢性白血病(诸如慢性髓细胞性(粒细胞性)白血病、慢性骨髓性白血病和慢性淋巴细胞性白血病)、真性红细胞增多症、淋巴瘤、霍奇金病、非霍奇金淋巴瘤(惰性和高级别形式)、多发性骨髓瘤、瓦尔登斯特罗姆巨球蛋白血症、重链疾病、骨髓增生异常综合症、毛细胞白血病和脊髓发育不良。
实体瘤是通常不包含囊肿或液体区域的异常组织块。实体瘤可以是良性或恶性的。不同类型的实体瘤根据形成它们的细胞类型而命名(诸如肉瘤、癌瘤和淋巴瘤)。实体瘤诸如肉瘤和癌瘤的实例包括纤维肉瘤、粘肉肉瘤、脂肪肉瘤、软骨肉瘤、骨肉瘤、滑膜瘤、间皮瘤、尤因氏肿瘤、平滑肌肉瘤、横纹肌肉瘤、结肠癌、淋巴性恶性肿瘤、胰腺癌、乳癌、肺癌、卵巢癌、前列腺癌、肝细胞癌、鳞状细胞癌、基底细胞癌、腺癌、汗腺癌、甲状腺髓样癌、乳头状甲状腺癌、嗜铬细胞瘤皮脂腺癌、乳头状癌、乳头状腺癌、髓样癌、支气管癌、肾细胞癌、肝癌、胆管癌、绒毛膜癌、威尔姆斯瘤、宫颈癌、睾丸肿瘤、精原细胞瘤、膀胱癌、黑色素瘤和CNS(中枢神经系统)肿瘤(诸如神经胶质瘤(诸如脑干神经胶质瘤和混合神经胶质瘤)、胶质母细胞瘤(也称为多形性成胶质细胞瘤)、星形胶质细胞瘤、CNS淋巴瘤、生殖细胞瘤、髓母细胞瘤、神经鞘瘤、颅咽管瘤、室管膜瘤、松果体瘤、血管母细胞瘤、听神经瘤、少突胶质细胞瘤、脑膜瘤、神经母细胞瘤、视网膜母细胞瘤和脑转移)。实体瘤抗原是在实体瘤上表达的抗原。在实施方案中，实体瘤抗原也在健康组织上低水平表达。实体瘤抗原及其相关疾病肿瘤的实例提供在表1中。
表1
Figure BDA0002948888430000031
Figure BDA0002948888430000041
在整个说明书中，除非上下文另外要求，否则词语“包含(comprise)”、包括(includes)”和“包括(including)”将被理解为暗示包括所述的
步骤或要素(成分或组分)或步骤或要素(成分或组分)组，但不排除任何其他步骤或要素或步骤或要素组。
短语“由......组成”意指包括并且限于短语“由......组成”之后的任何内容。因此，短语“由......组成”指示所列出的要素是必需或强制性的，而且不会存在其他要素。
短语“基本上由......组成”意指包括在短语之后列出的任何要素，并且可以包括不干扰或不影响本公开中针对所列要素所指定的活动或动作的其他要素。因此，短语“基本上由......组成”指示所列出的要素是必需的或强制性的，但是其他要素是可选的，并且取决于它们是否影响所列要素的活动或动作，可以存在或可以不存在。
术语“互补的”和“互补性”是指通过碱基配对规则关联在一起的多核苷酸(即核苷酸序列)。例如，序列“A-G-T”与序列“T-C-A”互补。互补性可以是“部分的”，其中仅一些核酸碱基根据碱基配对规则匹配，或在核酸之间可以存在“完全的”或“全部的”互补性。核酸链之间的互补程度对核酸链之间的杂交效率和强度有重要作用。
术语“对应于(corresponds to)”或“对应于(corresponding to)”是指(a)具有与参考多核苷酸序列的全部或一部分基本上相同或互补，或者编码与肽或蛋白质中的氨基酸序列相同的氨基酸序列的核苷酸序列的多核苷酸；或(b)具有与参考肽或蛋白质中的氨基酸序列基本上相同的氨基酸序列的肽或多肽。
术语“共刺激配体”是指抗原呈递细胞(例如，APC、树突状细胞、B细胞等)上的分子，其特异性结合T细胞上的同源共刺激分子，从而提供除了由例如TCR/CD3复合物与载有肽的MHC分子结合提供的主要信号外的一种信号，所述信号介导T细胞应答，包括增殖、激活、分化和其他细胞应答的至少一种。共刺激配体可以包括B7-1(CD80)、B7-2(CD86)、PD-L1、PD-L2、4-1BBL、OX40L、诱导型共刺激配体(ICOS-L)、细胞间粘附分子(ICAM)、CD30L、CD40、CD70、CD83、HLA-G、MICA、MICB、HVEM、淋巴毒素β受体、3/TR6、ILT3、ILT4、HVEM、CD7的配体、结合Toll配体受体的激动剂或抗体以及与B7-H3特异性结合的配体。共刺激配体还尤其包括与T细胞上存在的共刺激分子特异性结合的激动剂或抗体，诸如CD27、CD28、4-1BB、OX40、CD30、CD40、PD-1、ICOS、淋巴细胞功能相关抗原-1(LFA-1)、CD2、CD7、LIGHT、NKG2C、B7-H3以及特异性结合CD83的配体。
术语“共刺激分子”是指T细胞上的同源结合伴侣，其与共刺激配体特异性结合，从而介导T细胞的共刺激应答，诸如增殖。共刺激分子包括MHC I类分子、BTLA和Toll样受体。
术语“共刺激信号”是指与主要信号(诸如TCR/CD3连接)结合，导致T细胞增殖和/或关键分子上调或下调的信号。术语“疾病”和“病状”可以互换使用，或可以不同，因为特定的疾病或病状可能没有已知的致病物(因此病因尚未得到解决)，因此它还不是公认的疾病，但仅是一种不良病状或综合症，其中临床医生已鉴定出或多或少的特定症状的集合。术语“疾病”是受试者的健康状态，其中受试者不能维持体内平衡，并且其中如果疾病没有得到改善，则受试者的健康继续恶化。相比之下，受试者的“病症”是一种健康状态，其中动物能够维持体内平衡，但是其中动物的健康状态要比没有病症的情况下不利。如果不及时治疗，病症不一定会导致动物健康状态进一步下降。
术语“有效”是指足以实现期望的、预期的或意图的结果。例如，在治疗背景下的“有效量”可以是足以产生治疗或预防益处的化合物的量。术语“编码”是指多核苷酸诸如基因、cDNA或mRNA中的特定核苷酸序列在生物过程中用作合成其他聚合物和大分子的模板的固有特性，所述生物过程具有确定的核苷酸序列(即，rRNA、tRNA和mRNA)或确定的氨基酸序列以及由此产生的生物特性。因此，如果对应于基因的mRNA的转录和翻译在细胞或其他生物系统中产生蛋白质，则所述基因编码所述蛋白质。其核苷酸序列与mRNA序列相同(除了用“U”代替“T”以外)并且通常提供在序列表中的编码链以及用作基因或cDNA转录的模板的非编码链可被称为编码所述基因或cDNA的蛋白质或其他产物。
术语“外源的”是指并非天然存在于野生型细胞或生物体中，但通常通过分子生物学技术引入细胞中的分子。外源多核苷酸的实例包括编码所需蛋白质的载体、质粒和/或人造核酸构建体。关于多核苷酸和蛋白质，术语“内源的”或“天然的”是指可以在给定的野生型细胞或生物体中发现的天然存在的多核苷酸或氨基酸序列。同样，通过分子生物学技术从第一生物体分离并转移至第二生物体的特定多核苷酸序列通常被认为是相对于第二生物体的“外源”多核苷酸或氨基酸序列。在具体实施方案中，可以通过分子生物学技术将多核苷酸序列“引入”已经含有这种多核苷酸序列的微生物中，例如，以产生原本天然存在的多核苷酸序列的一个或多个其他拷贝，从而促进编码多肽的过表达。术语“表达”是指由其启动子驱动的特定核苷酸序列的转录和/或翻译。
术语“表达载体”是指包含重组多核苷酸的载体，所述重组多核苷酸包含可操作连接至待表达的核苷酸序列的表达控制序列。表达载体包括足够的用于表达的顺式作用要素；用于表达的其他要素可以由宿主细胞提供或提供在体外表达系统中。表达载体包括本领域已知的并入重组多核苷酸的所有载体，诸如粘粒、质粒(例如，裸露的或包含在脂质体中)和病毒(例如，慢病毒、逆转录病毒、腺病毒和腺相关病毒)。
术语“同源的”是指当两个比较的序列中的一个位置被相同的碱基或氨基酸单体亚基占据时，两个多肽之间或两个多核苷酸之间的序列相似性或序列同一性，例如，如果两个DNA分子中的每个中的一个位置被腺嘌呤占据，则分子在所述位置上是同源的。两个序列之间的同源性百分比是两个序列享有的匹配或同源位置数除以所比较的位置数×100的函数。例如，如果两个序列中10个位置中有6个是匹配或同源的，则两个序列是60％同源的。举例来说，DNA序列ATTGCC和TATGGC享有50％的同源性。当比对两个序列时进行比较，以得到最大同源性。
术语“免疫球蛋白”或“Ig”是指用作抗体的一类蛋白质。包括在此类蛋白质中的五个成员是IgA、IgG、IgM、IgD和IgE。IgA是存在于身体分泌物，诸如唾液、眼泪、母乳、胃肠道分泌物和呼吸道与泌尿生殖道的粘液分泌物中的一抗。IgG是最常见的循环抗体。在大多数受试者中，IgM是初次免疫应答中产生的主要免疫球蛋白。它是凝集、补体固定和其他抗体应答中最有效的免疫球蛋白，并且对于防御细菌和病毒很重要。IgD是不具有已知抗体功能但可以充当抗原受体的免疫球蛋白。IgE是通过暴露于过敏原时，引起肥大细胞和嗜碱性粒细胞释放介体而介导速发型超敏反应的免疫球蛋白。
术语“分离的”是指基本上或实质上不含在其天然状态下通常伴随其的组分的材料。所述材料可以是细胞或大分子，诸如蛋白质或核酸。例如，如本文所用的“分离的多核苷酸”是指已从以天然存在状态的方式位于其侧翼的序列中纯化的多核苷酸，例如已从通常与片段相邻的序列中去除的DNA片段。或者，如本文所用的“分离的肽”或“分离的多肽”等是指从其天然细胞环境以及从其与细胞的其他组分的缔合中体外分离和/或纯化肽或多肽分子。
术语“基本上纯化的”是指基本上不含在其天然状态下通常与其缔合的组分的材料。例如，基本上纯化的细胞是指在其天然存在或天然状态下从通常与其缔合的其他细胞类型中分离的细胞。在一些情况下，基本上纯化的细胞群是指同质的细胞群。在其他情况下，该术语简单地是指在其天然状态下从与其天然缔合的细胞中分离的细胞。在实施方案中，细胞在体外培养。在实施方案中，细胞并非在体外培养。
在本公开的上下文中，使用了以下常见存在的核酸碱基的缩写。“A”是指腺苷，“C”是指胞嘧啶，“G”是指鸟苷，“T”是指胸苷，并且“U”是指尿苷。
除非另有说明，否则“编码氨基酸序列的核苷酸序列”包括彼此为简并形式并且编码相同氨基酸序列的所有核苷酸序列。编码蛋白质或RNA的短语核苷酸序列也可以包括内含子，其程度为编码蛋白质的核苷酸序列在某些形式中可以包含一个或多个内含子。
术语“慢病毒”是指逆转录病毒科的一个属。慢病毒在逆转录病毒中是独特的，其能够感染非分裂细胞；它们可以将大量的遗传信息递送到宿主细胞的DNA中，因此它们是基因递送载体的最有效方法之一。此外，使用慢病毒能够将遗传信息整合到宿主染色体中，从而产生稳定转导的遗传信息。HIV、SIV和FIV是慢病毒的所有实例。衍生自慢病毒的载体提供了在体内实现显著水平的基因转移的手段。
术语“调节”是指与不存在治疗或化合物的情况下受试者中的反应水平相比，和/或与其他相同但未治疗的受试者中的反应水平相比，介导受试者中反应水平的可检测的增加或降低。所述术语涵盖干扰和/或影响天然信号或反应，从而在受试者、优选地人中介导有益的治疗反应。
当核酸与另一个核酸序列处于功能关系时，所述核酸是“可操作连接的”。例如，如果前序列或分泌前导序列的DNA表达为参与多肽分泌的前蛋白，则所述DNA可操作地连接至多肽的DNA；如果启动子或增强子影响序列的转录，则所述启动子或增强子可操作地连接至编码序列；或如果核糖体结合位点被定位以便于翻译，则所述核糖体结合位点可操作地连接至编码序列。
术语“在转录控制下”是指启动子可操作地连接至多核苷酸并相对于多核苷酸并处于正确的位置和方向，以控制由RNA聚合酶进行的转录开始和多核苷酸表达。
术语“过度表达的”肿瘤抗原或肿瘤抗原的“过度表达”旨在指示相对于来自特定组织或器官的正常细胞中的表达水平，来自患者的所述组织或器官中的疾病区域(例如实体瘤)的细胞中肿瘤抗原的异常表达水平。可以通过本领域已知的标准测定来确定患有特征在于肿瘤抗原过表达的实体瘤或血液恶性肿瘤的患者。
术语组合物的“肠胃外施用”包括例如皮下(s.c.)、静脉内(i.v.)、肌内(i.m.)、胸骨内注射或输注技术。
术语“患者”、“受试者”和“个体”等在本文可互换使用，并且是指适用于本文描述的方法的任何人、动物或活生物体。在某些非限制性实施方案中，患者、受试者或个体是人或动物。在实施方案中，术语“受试者”旨在包括在其中可以引发免疫应答的活生物体(例如，哺乳动物)。受试者的实例包括人和动物，诸如狗、猫、小鼠、大鼠及其转基因物种。
需要治疗或其有需要的受试者包括患有需要治疗的疾病、病状或病症的受试者。其有需要的受试者还包括需要治疗以预防疾病、病状或病症的受试者。在实施方案中，疾病是癌症。
术语“多核苷酸”或“核酸”是指mRNA、RNA、cRNA、rRNA、cDNA或DNA。所述术语通常是指长度至少为10个碱基的聚合形式核苷酸，核糖核苷酸或脱氧核苷酸或修饰形式的任一类型核苷酸。所述术语包括所有形式的核酸，包括单链和双链形式的核酸。
术语“多核苷酸变体”和“变体”等是指与参考多核苷酸序列显示基本序列同一性的多核苷酸或在下文定义的严格条件下与参考序列杂交的多核苷酸。这些术语还涵盖通过添加、缺失或替换至少一个核苷酸而与参考多核苷酸区分开的多核苷酸。因此，术语“多核苷酸变体”和“变体”包括其中一个或多个核苷酸已被添加或缺失或被不同核苷酸代替的多核苷酸。就这一点而言，本领域众所周知，可以对参考多核苷酸进行某些改变，包括突变、添加、缺失和替换，从而使改变后的多核苷酸保留参考多核苷酸的生物功能或活性或相对于参考多核苷酸具有增加的活性(即优化的)。多核苷酸变体包括例如与本文描述的参考多核苷酸序列具有至少50％(和至少51％至至少99％以及其间的所有整数百分比，例如90％、95％或98％)序列同一性的多核苷酸。术语“多核苷酸变体”和“变体”还包括天然存在的等位基因变体和直系同源物。
术语“多肽”、“多肽片段”、“肽”和“蛋白质”在本文中可互换使用，是指氨基酸残基的聚合物及其变体和合成类似物。因此，这些术语适用于氨基酸聚合物，其中一个或多个氨基酸残基是合成的非天然存在的氨基酸，诸如相应天然存在的氨基酸的化学类似物，以及适用于天然存在的氨基酸聚合物。在某些方面，多肽可以包括酶促多肽或“酶”，其通常催化各种化学反应(即，增加其速率)。
术语“多肽变体”是指通过添加、缺失或替换至少一个氨基酸残基而与参考多肽序列区分开的多肽。在实施方案中，多肽变体通过一个或多个替换而与参考多肽区分开，所述一个或多个替换可以是保守的或非保守的。在实施方案中，多肽变体包含保守替换，并且就这一点而言，在本领域中众所周知，可以将一些氨基酸改变为具有大致相似特性的其他氨基酸，而不改变多肽活性的性质。多肽变体还涵盖其中一个或多个氨基酸已被添加或缺失或被不同氨基酸残基代替的多肽。
术语“启动子”是指由细胞的合成机制识别或引入合成机制，开始多核苷酸序列的特异性转录所需要的DNA序列。术语“表达控制序列”是指在特定宿主生物体中表达可操作连接的编码序列所必需的DNA序列。适用于原核生物的控制序列例如包括启动子，任选地操纵子序列和核糖体结合位点。已知真核细胞利用启动子、聚腺苷酸化信号和增强子。术语“结合(bind)”、“结合(binds)”或“与......相互作用”是指识别并粘附于样品或生物体中第二分子但基本上不识别或粘附于样品中其他结构无关分子的分子。如本文所用关于抗体的术语“特异性结合”，是指识别特异性抗原但基本上不识别或结合样品中其他分子的抗体。例如，特异性结合来自一种物种的抗原的抗体也可以结合来自一种或多种物种的抗原。但是，这种种间反应性本身并不会改变抗体的特异性分类。在另一个实例中，特异性结合抗原的抗体也可以结合不同等位基因形式的抗原。然而，这种交叉反应性本身并不会改变抗体的特异性分类。在一些情况下，术语“特异性结合(specific binding)”或“特异性结合(specifically binding)”可用于指抗体、蛋白质或肽与第二化学物种的相互作用，意味着相互作用取决于化学物种上的特定结构(例如，抗原决定簇或表位)存在；例如，抗体识别并结合特定的蛋白质结构，而不是结合任何蛋白质。如果抗体对表位“A”具有特异性，则在包含标记“A”和抗体的反应中存在包含表位A(或游离、未标记的A)的分子将减少与抗体结合的标记A的量。
“结合蛋白”是能够非共价结合另一种分子的蛋白质。结合蛋白可以例如结合DNA分子(DNA结合蛋白)、RNA分子(RNA结合蛋白)和/或蛋白质分子(蛋白质结合蛋白)。在蛋白质结合蛋白的情况下，结合蛋白可以与自身结合(形成同二聚体、同三聚体等)和/或可以与不同蛋白质的一个或多个分子结合。结合蛋白可以具有多于一种类型的结合活性。例如，锌指蛋白具有DNA结合、RNA结合、和蛋白质结合的活性。
“锌指DNA结合蛋白”(或结合结构域)是一种蛋白质或较大蛋白内的结构域，其通过一个或多个锌指以序列特异性方式结合DNA，所述一个或多个锌指是通过锌离子配位稳定结构的结合结构域内的氨基酸序列区域。术语锌指DNA结合蛋白通常缩写为锌指蛋白或ZFP。
锌指结合结构域可以被“工程化”以结合预定的核苷酸序列，例如通过对天然存在的锌指蛋白的识别螺旋区进行工程化(改变一个或多个氨基酸)来实现。此外，锌指结合结构域可以融合DNA切割域以形成靶向特定所需DNA序列的锌指核酸酶(ZFN)。例如，一对ZFN(例如，ZFN左臂(left arm)和ZFN右臂(right arm))可以被工程化以靶向和引起特定所需DNA序列(例如，TRAC基因)的修饰。
“切割”是指DNA分子的共价主链断裂。可以通过各种方法来进行切割，包括但不限于磷酸二酯键的酶促或化学水解。单链切割和双链切割都是有可能的，双链切割可以由两个不同的单链切割事件而引起。DNA切割可以导致钝端或交错端的产生。在实施方案中，融合多肽用于靶向的双链DNA切割。
“靶位点”或“靶序列”是定义结合分子将结合的核酸的一部分的核酸序列，条件是存在足够的结合条件。例如，序列5'GAATTC 3'是Eco Rl限制性内切酶的靶位点。
“融合”分子是其中两个或更多个亚基分子优选共价连接的分子。亚基分子可以是相同化学类型的分子，或可以是不同化学类型的分子。第一类型的融合分子的实例包括但不限于融合蛋白(例如，ZFP DNA结合结构域和一个或多个激活结构域之间的融合)和融合核酸(例如，编码上述融合蛋白的核酸)。第二类型的融合分子的实例包括但不限于形成三链体的核酸与多肽之间的融合，以及小沟结合物(minor groove binder)与核酸之间的融合。
融合蛋白在细胞中的表达可以由融合蛋白向细胞的递送或编码融合蛋白的多核苷酸向细胞的递送引起，其中转录多核苷酸，并且翻译转录物以生成融合蛋白。反式剪接、多肽切割和多肽连接也可以参与蛋白质在细胞中的表达。在本公开的其他地方提出了用于多核苷酸和多肽向细胞递送的方法。
基因表达的“调节”是指基因活性的变化。表达的调节可以包括但不限于基因激活和基因抑制。基因组编辑(例如，切割、改变、失活、随机突变)可以用来调节表达。基因失活是指与不包括本文所述的ZFP的细胞相比，基因表达的任何减少。因此，基因失活可以是部分的或全部的。
“感兴趣的区域”是细胞染色质的任何区域，例如像基因、或基因内或与基因相邻的非编码序列，其中期望结合外源分子。结合可以是出于靶向DNA切割和/或靶向重组的目的进行的。感兴趣的区域可以例如存在于染色体、游离体、细胞器基因组(例如线粒体、叶绿体)或感染性病毒基因组中。感兴趣的区域可以在基因的编码区内，在转录的非编码区内，例如像前导序列、拖尾序列或内含子，或在非转录区内，编码区的上游或下游。感兴趣的区域的长度可以小到单个核苷酸对或高达2,000个核苷酸对，或任何整数值的核苷酸对。
“统计学上显著的”意指结果不太可能是偶然发生的。统计学显著性可以通过本领域已知的任何方法确定。常用的显著性度量包括p值，所述p值是在虚假设为真时观察到的事件发生的频率或概率。如果获得的p值小于显著性水平，则拒绝虚假设。在简单情况下，显著性水平被定义为0.05或更小的p值。“减少”或“降低”或“较少”的量通常是“统计学上显著的”或生理上显著的量，并且可包括与本文描述的量或水平相比约1.1、1.2、1.3、1.4、1.5、1.6、1.7、1.8、1.9、2、2.5、3、3.5、4、4.5、5、6、7、8、9、10、15、20、30、40或50或更多倍(例如，100、500、1000倍)(包括介于1和大于1之间的所有整数和小数点，例如1.5、1.6、1.7、1.8等)的减少量。
术语“刺激”是指由刺激分子(例如，TCR/CD3复合物)与其同源配体结合从而介导信号转导事件而诱导的初次应答，诸如经由TCR/CD3复合物进行的信号转导。刺激可以介导某些分子表达的改变，诸如TGF-β的下调和/或细胞骨架结构的再组织。针对初次应答，CD3ζ不是CAR构建体的唯一适合的主要信号传导结构域。例如，早在1993年，CD3ζ和FcRγ都被认为是CAR分子的功能性主要信号传导结构域。Eshhar等人,"Specific activation andtargeting of cytotoxic lymphocytes through chimeric single chains consistingof antibody-binding domains and the gamma or zeta subunits of theimmunoglobulin and T cell receptors"PNAS,1993Jan 15；90(2):720-4示出了两种CAR构建体，其中scFv被融合到“FcRγ链或CD3复合链”，从而触发了T细胞激活和靶细胞。值得注意的是，如Eshhar等人所证明，包含仅初级信号传导结构域CD3ζ或FcRγ的CAR构建体在不存在共刺激结构域的情况下是具有功能性的。这些年来，还开发了其他基于非CD3ζ的CAR构建体。例如，Wang等人("A Chimeric Antigen Receptor(CARs)Based Upon a KillerImmunoglobulin-Like Receptor(KIR)Triggers Robust Cytotoxic Activity in SolidTumors"Molecular Therapy,vol.22,no.Suppl.1,May 2014,第S57页)测试了一种CAR分子，其中scFv被融合到“杀伤性免疫球蛋白样受体(KIR)的跨膜结构域和胞质结构域。Wang等报道了“靶向间皮素的基于KIR的CAR(SS 1-KIR)触发了与基于CD3的CAR相当的抗原特异性细胞毒性活性和细胞因子产生”。来自同一团队的第二篇出版物，Wang等人("Generationof Potent T-cell Immunotherapy for Cancer Using DAP12-Based,Multichain,Chimeric Immunoreceptors"Cancer Immunol Res.2015Jul；3(7):815-26)示出了一种CAR分子，其中用于抗原识别的单链可变片段被融合到KIR2DS2(刺激性杀伤性免疫球蛋白样受体(KIR))的跨膜结构域和胞质结构域，当该CAR分子引入到具有DAP12(含有基于免疫酪氨酸的激活基序的适配子)的人T细胞中时，它在体外和体内均具有功能性。
术语“刺激分子”是指T细胞上与存在于抗原呈递细胞上的同源刺激配体特异性结合的分子。例如，来源于刺激分子的功能性信号传导结构域是与T细胞受体复合物缔合的ζ链。
术语“刺激配体”是指以下配体，所述配体当存在于抗原呈递细胞(例如，APC、树突状细胞、B细胞等)上时，可以与细胞例如T细胞上的同源结合伴侣(本文称为“刺激分子”)特异性结合，从而介导T细胞的初次应答，包括激活、免疫应答的开始、增殖和相似过程。刺激配体在本领域中是众所周知的，并且尤其涵盖载有肽的MHC I类分子、抗CD3抗体、超激动剂抗CD28抗体和超激动剂抗CD2抗体。
术语“治疗的”是指治疗和/或预防。通过抑制、缓解或根除疾病状态或减轻疾病状态的症状可获得治疗效果。
术语“治疗有效量”是指本发明的化合物的量，其将引发研究人员、兽医、医生或另外临床医生所寻求的组织、系统或受试者的生物或医学反应。术语“治疗有效量”包括当施用时足以防止所治疗的病症或疾病的一种或多种病征或症状的发展或在某种程度上对其减轻的化合物的量。治疗有效量将取决于化合物、疾病及其严重程度以及待治疗受试者的年龄、体重等而变化。
术语“治疗疾病”是指降低受试者经历的疾病或病症的至少一种病征或症状的频率或严重程度。
术语“转染的”或“转化的”或“转导的”是指将外源核酸转移或引入宿主细胞中的过程。“转染的”或“转化的”或“转导的”细胞是已用外源核酸转染、转化或转导的细胞。所述细胞包括原代受试者细胞及其后代。
术语“载体”是指包含分离的核酸并且可用于将分离的核酸体外和体内(在受试者体内)递送至细胞内部的多核苷酸。在本领域中已知许多载体，包括线性多核苷酸、与离子或两亲化合物缔合的多核苷酸、质粒和病毒。因此，术语“载体”包括自主复制质粒或病毒。所述术语还包括促进核酸转移到细胞中的非质粒和非病毒化合物，诸如例如聚赖氨酸化合物、脂质体等。病毒载体的实例包括腺病毒载体、腺伴随病毒载体、逆转录病毒载体等。例如，慢病毒是复杂的逆转录病毒，其除了常见的逆转录病毒基因gag、pol和env外，还包含具有调节或结构功能的其他基因。慢病毒载体是本领域众所周知的。慢病毒的一些实例包括人免疫缺陷病毒：HIV-1、HIV-2和猿猴免疫缺陷病毒：SIV。慢病毒载体是通过多重减毒HIV毒力基因生成的，例如，使基因env、vif、vpr、vpu和nef缺失，从而使得载体具有生物安全性。
范围：在整个公开内容中，可以以范围形式来呈现本公开的各个方面。应当理解，范围格式的描述仅是为了方便和简洁，而不应被解释为对本公开范围的不可改变的限制。因此，对范围的描述应被认为已明确公开了所有可能的子范围以及所述范围内的各个数值。例如，对范围的描述诸如从1到6应被认为已明确公开了子范围，诸如从1到3、从1到4、从1到5、从2到4、从2到6、从3到6等，以及所述范围内的单个数字，例如1、2、2.7、3、4、5、5.3和6。无论范围的宽度如何，这都适用。本公开的实施方案涉及使用嵌合抗原受体(CAR)细胞来治疗癌症。实施方案涉及编码CAR的分离的核酸序列，其中CAR包括细胞外结构域、跨膜结构域和细胞内结构域，其中CAR的细胞外结构域结合实体瘤的抗原。例如，转录数据表明诸如SLC6A3、KISS1R、QRFPR等的抗原在正常组织中的表达非常低，但这类抗原在与肾癌相关的细胞中表达较高。一些抗原的信息提供在下表2中。
表2
Figure BDA0002948888430000091
Figure BDA0002948888430000101
在实施方案中，CAR的细胞外结构域结合SIGLEC15。SIGLEC15是表达在细胞膜上，识别唾液酸聚糖的受体蛋白。转录数据预测它在尿路上皮癌细胞中过表达，并在正常组织中低水平表达。它主要存在于脾和淋巴结中，其他免疫器官也有一定量的低表达。例如，CAR的细胞外结构域结合SIGLEC15，所述SIGLEC15具有SEQ ID NO:17的氨基酸序列。在实施方案中，细胞外结构域包含SEQ ID NOs:45-56的氨基酸序列之一。实施方案涉及引发和/或增强患有实体瘤的受试者中T细胞应答或治疗受试者的实体瘤的方法，所述方法包括向受试者施用有效量的包含CAR的T细胞。在实施方案中，肿瘤与尿路上皮癌相关。受试者中的T细胞应答是指与辅助、杀伤、调节和其他类型的T细胞相关的细胞介导免疫。例如，T细胞应答可以包括诸如在免疫过程中协助其他白细胞以及识别和破坏病毒感染的细胞和肿瘤细胞的活动。受试者中的T细胞应答可通过各种指标进行测量，诸如T细胞杀伤的病毒感染细胞和/或肿瘤细胞的数量，与病毒感染细胞和/或肿瘤细胞共同培养时T细胞释放的细胞因子的量、受试者中T细胞的增殖水平、T细胞的表型改变(例如记忆T细胞改变)以及受试者中T细胞的长寿或寿命水平。
在实施方案中，可通过将CAR T细胞与抗原阳性细胞共同培养来测量CAR T细胞的杀伤效力来进行体外杀伤测定。与不表达相应抗原的对照细胞相比，通过显示与CAR T细胞共同培养的相应抗原阳性细胞的数量减少以及IFNγ、TNFα等的释放增加，CAR T细胞可被认为对相应抗原阳性细胞具有杀伤作用。此外，可以测试CAR T细胞的体内抗肿瘤活性。例如，可以使用本文描述的抗原在免疫缺陷小鼠中建立异种移植模型。在过去的二十年中，将人癌细胞或肿瘤活检组织异种移植到免疫缺陷的啮齿动物(异种移植模型)中，构成了开发新型癌症治疗剂的主要临床前筛选(Song等人,Cancer Res.PMC 2014 Aug 21和Morton等人,Nature Protocols,2,-247-250(2007))。为了评价CAR T细胞的体内抗肿瘤活性，对具有肿瘤异种移植物的免疫缺陷小鼠进行CAR T细胞抗肿瘤活性(例如，小鼠肿瘤减少和小鼠血液IFNγ、TNFα等减少)评价。
术语“嵌合抗原受体”或可替代地“CAR”是指包含至少细胞外抗原结合结构域、跨膜结构域和细胞内信号传导结构域(例如，胞质结构域)的重组多肽构建体。在实施方案中，CAR多肽构建体中的结构域在相同多肽链上(例如包含嵌合融合蛋白)。在实施方案中，CAR多肽的结构域不在同一分子上，例如彼此不连续或在不同多肽链上。
在实施方案中，细胞内信号传导结构域可以包括衍生自本文所述的刺激分子和/或共刺激分子的功能性信号传导结构域。在实施方案中，细胞内信号传导结构域包括衍生自初级信号传导结构域(例如，CD3-ζ的初级信号传导结构域)的功能性信号传导结构域。在实施方案中，细胞内信号传导结构域还包括一个或多个衍生自至少一种共刺激分子的功能性信号传导结构域。共刺激信号传导区是指CAR的一部分，其包括共刺激分子的细胞内结构域。共刺激分子可以包括用于诱导淋巴细胞的有效应答(对抗原的应答)的细胞表面分子。
在CAR的细胞外结构域与跨膜结构域之间，可以并入间隔域。如本文所用，术语“间隔域”通常意指在多肽链中起到将跨膜结构域连接至细胞外结构域和/或胞质结构域作用的任何寡肽或多肽。间隔域可以包含高达300个氨基酸、10至100个氨基酸、或25至50个氨基酸。CAR的细胞外结构域可包括靶向特定肿瘤标志物(例如，肿瘤抗原)的抗原结合结构域(例如，scFv、单域抗体或TCR(诸如TCRα结合结构域或TCRβ结合结构域))。肿瘤抗原是由肿瘤细胞产生的引发免疫应答的蛋白质，特别是T细胞介导的免疫应答。肿瘤抗原是本领域众所周知的，并且包括例如神经胶质瘤相关抗原、癌胚抗原(CEA)、β-人绒毛膜促性腺激素、甲胎蛋白(AFP)、凝集素反应性AFP、甲状腺球蛋白、RAGE-1、MN-CA IX、人端粒酶逆转录酶、RU1、RU2(AS)、肠羧酸酯酶、mut hsp70-2、M-CSF、前列腺酶(prostase)、前列腺特异性抗原(PSA)、PAP、NY-ESO-1、LAGE-1a、p53、前列腺特异性蛋白(prostein)、PSMA、Her2/neu、存活素和端粒酶、前列腺癌肿瘤抗原-1(PCTA-1)、MAGE、ELF2M、中性粒细胞弹性蛋白酶、肝配蛋白B2、CD22、胰岛素生长因子(IGF)-I、IGF-II、IGF-I受体和间皮素。例如，当CAR结合的抗原是CD19时，其CAR被称为CD19CAR。
在实施方案中，细胞外配体结合结构域包含scFv，其包含通过柔性接头连接的靶抗原特异性单克隆抗体的轻链可变(VL)区和重链可变(VH)区。通过使用短连接肽连接轻链可变区和/或重链可变区来制备单链可变区片段(Bird等人,Science 242:423-426,1988)。连接肽的实例是具有氨基酸序列(GGGGS)3(SEQ ID:24)的GS接头，其在一个可变区的羧基末端和另一可变区的氨基末端之间桥接约3.5nm。已设计并使用了其他序列的接头(Bird等人,1988,同上)。通常，接头可以是短的柔性多肽，其包含约20个或更少的氨基酸残基。反过来，可以对接头进行修饰以实现其他功能，诸如药物附接或对固体支持物的附接。单链变体可以重组或合成产生。针对scFv的合成产生，可以使用自动合成仪。针对scFv的重组产生，可以将合适的含有编码scFv的多核苷酸的质粒引入合适的宿主细胞中，所述宿主细胞可以是真核生物，诸如酵母、植物、昆虫或哺乳动物细胞，或者可以是原核生物，诸如大肠杆菌。编码感兴趣的scFv的多核苷酸可以通过常规操作诸如多核苷酸的连接来制备。可以使用本领域已知的标准蛋白质纯化技术分离所得的scFv。
在实施方案中，肿瘤抗原包括HER2、CD19、CD20、CD22、κ或轻链、CD30、CD33、CD123、CD38、ROR1、ErbB3/4、EGFR、EGFRvIII、EphA2、FAP、癌胚抗原、EGP2、EGP40、间皮素、TAG72、PSMA、NKG2D配体、B7-H6、IL-13受体α2、IL-11受体α、MUC1、MUC16、CA9、GD2、GD3、HMW-MAA、CD171、Lewis Y、G250/CAIX、HLA-AI MAGE A1、HLA-A2 NY-ESO-1、PSC1、叶酸受体-α、CD44v7/8、8H9、NCAM、VEGF受体、5T4、胎儿型AchR、NKG2D配体、CD44v6、TEM1、TEM8或由肿瘤表达的病毒相关抗原。在实施方案中，CAR的结合要素可以包括任何抗原结合部分，所述抗原结合部分在与其同源抗原结合时会影响肿瘤细胞，使得肿瘤细胞无法生长，或被促进死亡或减少。
在实施方案中，CAR的细胞外结构域结合KISS1R。KISS1R是一种甘丙肽样G蛋白偶联受体，其与由转移抑制基因KISS1编码的肽-亲吻素(转移抑制素)结合。KISS1 R可参与内分泌功能调节。例如，CAR的细胞外结构域结合KISS1R，所述KISS1R具有SEQ ID NO:19的氨基酸序列。在实施方案中，CAR的细胞外结构域包含SEQ ID NOs:71和72的氨基酸序列之一。实施方案涉及引发和/或增强患有实体瘤的受试者中T细胞应答或治疗受试者的实体瘤的方法，其中所述方法包括施用有效量的包含CAR的T细胞。在实施方案中，实体瘤与肾癌相关。
在实施方案中，CAR的细胞外结构域结合CLDN6。CLDN6是紧密连接链的组成部分，是密封蛋白(claudin)家族的成员(一种完整膜蛋白)。转录数据预测紧密连接链的组成部分在子宫内膜癌、尿路上皮癌中高度表达，而在正常组织中低体积表达，所述紧密连接链的组成部分是密封蛋白家族的成员。例如，CAR的细胞外结构域结合CLDN6，所述CLDN6具有SEQID NO:22的氨基酸序列。在实施方案中，CAR的细胞外结构域包含SEQ ID NOs:29-44的氨基酸序列之一。实施方案涉及引发和/或增强患有实体瘤的受试者中T细胞应答或治疗受试者的实体瘤的方法，其中所述方法包括施用有效量的包含CAR的T细胞。在实施方案中，实体瘤与子宫内膜癌和/或尿路上皮癌相关。
在实施方案中，CAR的细胞外结构域结合MUC16。MUC21和MUC16是大型膜结合糖蛋白，属于粘蛋白家族。粘蛋白是O-糖基化蛋白，其在上皮表面形成保护性粘液屏障方面起着至关重要的作用。针对食管癌，MUC21对食管的表达受限。MUC16在正常组织中表达较低，在子宫内膜中也表达较低。在卵巢癌中，MUC16却高度表达。例如，CAR的细胞外结构域结合MUC16，所述MUC16具有SEQ ID NO:6的氨基酸序列。在实施方案中，CAR的细胞外结构域包含SEQ ID NOs:63-70的氨基酸序列之一。实施方案涉及引发和/或增强患有实体瘤的受试者中T细胞应答或治疗受试者的实体瘤的方法，其中所述方法包括施用有效量的包含CAR的T细胞。在实施方案中，实体瘤与卵巢癌相关。在实施方案中，CAR的细胞外结构域结合SLC6A3。SLC6A3是多巴胺转运蛋白，是依赖钠和氯的神经递质转运蛋白家族的成员。例如，CAR的细胞外结构域结合SLC6A3，所述SLC6A3具有SEQ ID NO:18的氨基酸序列。实施方案包括引发和/或增强患有实体瘤的受试者中T细胞应答或治疗受试者的实体瘤的方法，其中所述方法包括施用有效量的包含CAR的T细胞。在实施方案中，肿瘤包括肾癌。
在实施方案中，CAR的细胞外结构域结合QRFPR。QRFPR是焦谷氨酸化RF酰胺肽受体，并且可与其配体QRFP参与脂肪形成。例如，CAR的细胞外结构域结合QRFPR，所述QRFPR具有SEQ ID NO:20的氨基酸序列。实施方案涉及引发和/或增强患有实体瘤的受试者中T细胞应答或治疗受试者的实体瘤的方法，其中所述方法包括施用有效量的包含CAR的T细胞。在实施方案中，实体瘤与肾癌相关。在实施方案中，CAR的细胞外结构域结合GPR119。GPR119是G蛋白偶联受体视紫红质亚科的成员，在胰腺和胃肠道中低表达，并可以涉及葡萄糖稳态。转录数据预测在胰腺癌中高度表达。例如，CAR的细胞外结构域结合GPR119，所述GPR119具有SEQ ID NO:21的氨基酸序列。实施方案涉及引发和/或增强患有实体瘤的受试者中T细胞应答或治疗受试者的实体瘤的方法，其中所述方法包括施用有效量的包含CAR的T细胞。在实施方案中，肿瘤与胰腺癌相关。
在实施方案中，CAR的细胞外结构域结合UPK2。UPK2是一种不对称单位膜的高度保守的尿路上皮特异性整合膜蛋白，其主要在膀胱正常组织中表达和在尿路上皮癌(包括膀胱癌)的膀胱中表达。例如，CAR的细胞外结构域结合UPK2，所述UPK2具有SEQ ID NO:1的氨基酸序列。实施方案涉及引发和/或增强患有实体瘤的受试者中T细胞应答或治疗受试者的实体瘤的方法，其中所述方法包括施用有效量的包含CAR的T细胞。在实施方案中，实体瘤与尿路上皮癌和/或膀胱癌相关。
在实施方案中，CAR的细胞外结构域结合ADAM12。ADAM12是与蛇毒分解素结构相关的蛋白家族的成员，其涉及细胞-细胞和细胞-基质的相互作用，并在诸如胎盘和乳腺/胰腺癌等肿瘤中高度表达。例如，CAR的细胞外结构域结合ADAM12，所述ADAM12具有SEQ ID NO:2的氨基酸序列。实施方案涉及引发和/或增强患有实体瘤的受试者中T细胞应答或治疗受试者的实体瘤的方法，其中所述方法包括施用有效量的包含CAR的T细胞。在实施方案中，实体瘤与乳腺癌和/或胰腺癌相关。
在实施方案中，CAR的细胞外结构域结合SLC45A3。SLC45A3是一种质膜蛋白，正常组织主要表达在前列腺癌的前列腺中。例如，CAR的细胞外结构域结合SLC45A3，所述SLC45A3具有SEQ ID NO:3的氨基酸序列。实施方案涉及引发和/或增强患有实体瘤的受试者中T细胞应答或治疗受试者的实体瘤的方法，其中所述方法包括施用有效量的包含CAR的T细胞。在实施方案中，实体瘤与前列腺癌相关。在实施方案中，CAR的细胞外结构域结合ACPP。ACPP是一种催化正磷酸单酯转化为醇和正磷酸的酶，其包含跨膜结构域并位于质膜-内体-溶酶体途径中。正常组织在前列腺癌的前列腺中特异性表达。例如，CAR的细胞外结构域结合ACPP，所述ACPP具有SEQ ID NO:4的氨基酸序列。实施方案涉及引发和/或增强患有实体瘤的受试者中T细胞应答或治疗受试者的实体瘤的方法，其中所述方法包括施用有效量的包含CAR的T细胞。在实施方案中，实体瘤与前列腺癌相关。在实施方案中，CAR的细胞外结构域结合MUC21。MUC21和MUC16是大型膜结合糖蛋白，属于粘蛋白家族。粘蛋白是O-糖基化蛋白，其在上皮表面形成保护性粘液屏障方面起着至关重要的作用。当受试者患有食管癌时，MUC21对食管的表达受限。例如，CAR的细胞外结构域结合MUC21，所述MUC21具有SEQID NO:5的氨基酸序列。实施方案涉及引发和/或增强患有实体瘤的受试者中T细胞应答或治疗受试者的实体瘤的方法，其中所述方法包括施用有效量的包含CAR的T细胞。在实施方案中，实体瘤与食管癌相关。
在实施方案中，CAR的细胞外结构域结合MS4A12。MS4A12是一种在结肠细胞顶膜中发现的细胞表面蛋白，其在结肠中表达受限，并可用于治疗结肠直肠癌。例如，CAR的细胞外结构域结合MS4A12，所述MS4A12具有SEQ ID NO:7的氨基酸序列。实施方案涉及引发和/或增强患有实体瘤的受试者中T细胞应答或治疗受试者的实体瘤的方法，其中所述方法包括施用有效量的包含CAR的T细胞。在实施方案中，实体瘤与结肠直肠癌相关。
在实施方案中，CAR的细胞外结构域结合ALPP。ALPP是一种碱性磷酸酶，一种催化磷酸单酯水解的金属酶。ALPP的表达限于胎盘。在卵巢腺癌、浆液性囊腺癌和其他卵巢癌细胞中检测到强烈的ALPP异位表达。例如，CAR的细胞外结构域结合ALPP，所述ALPP具有SEQID NO:8的氨基酸序列。实施方案涉及引发和/或增强患有实体瘤的受试者中T细胞应答或治疗受试者的实体瘤的方法，其中所述方法包括施用有效量的包含CAR的T细胞。在实施方案中，实体瘤与子宫内膜癌相关。
在实施方案中，CAR的细胞外结构域结合SLC2A14。例如，CAR的细胞外结构域结合SLC2A14，所述SLC2A14具有SEQ ID NO:9的氨基酸序列。实施方案涉及引发和/或增强患有实体瘤的受试者中T细胞应答或治疗受试者的实体瘤的方法，其中所述方法包括施用有效量的包含CAR的T细胞。在实施方案中，肿瘤与睾丸癌相关。
在实施方案中，CAR的细胞外结构域结合GS1-259H13.2。例如，CAR的细胞外结构域结合GS1-259H13.2，所述GS1-259H13.2具有SEQ ID NO:10的氨基酸序列。实施方案涉及引发和/或增强患有实体瘤的受试者中T细胞应答或治疗受试者的实体瘤的方法，其中所述方法包括施用有效量的包含CAR的T细胞。在实施方案中，肿瘤与甲状腺癌、或神经胶质瘤、或睾丸癌相关。
在实施方案中，CAR的细胞外结构域结合ERVFRD-1。例如，CAR的细胞外结构域结合ERVFRD-1，所述ERVFRD-1具有SEQ ID NO:11的氨基酸序列。实施方案涉及引发和/或增强患有实体瘤的受试者中T细胞应答或治疗受试者的实体瘤的方法，其中所述方法包括施用有效量的包含CAR的T细胞。在实施方案中，肿瘤与肾癌或尿道癌相关。在实施方案中，CAR的细胞外结构域结合ADGRG2。例如，CAR的细胞外结构域结合ADGRG2，所述ADGRG2具有SEQ IDNO:12的氨基酸序列。实施方案涉及引发和/或增强患有实体瘤的受试者中T细胞应答或治疗受试者的实体瘤的方法，其中所述方法包括施用有效量的包含CAR的T细胞。在实施方案中，肿瘤与卵巢癌相关。
在实施方案中，CAR的细胞外结构域结合ECEL1。例如，CAR的细胞外结构域结合ECEL1，所述ECEL1具有SEQ ID NO:13的氨基酸序列。实施方案涉及引发和/或增强患有实体瘤的受试者中T细胞应答或治疗受试者的实体瘤的方法，其中所述方法包括施用有效量的包含CAR的T细胞。在实施方案中，肿瘤与子宫内膜癌相关。
在实施方案中，CAR的细胞外结构域结合CHRNA2。例如，CAR的细胞外结构域结合CHRNA2，所述CHRNA2具有SEQ ID NO:14的氨基酸序列。实施方案涉及引发和/或增强患有实体瘤的受试者中T细胞应答或治疗受试者的实体瘤的方法，其中所述方法包括施用有效量的包含CAR的T细胞。在实施方案中，肿瘤与前列腺癌相关。
在实施方案中，CAR的细胞外结构域结合GP2。例如，CAR的细胞外结构域结合GP2，所述GP2具有SEQ ID NO:15的氨基酸序列。实施方案涉及引发和/或增强患有实体瘤的受试者中T细胞应答或治疗受试者的实体瘤的方法，其中所述方法包括施用有效量的包含CAR的T细胞。在实施方案中，肿瘤与胰腺癌相关。
在实施方案中，CAR的细胞外结构域结合PSG9。例如，CAR的细胞外结构域结合PSG9，所述PSG9具有SEQ ID NO:16的氨基酸序列。实施方案涉及引发和/或增强患有实体瘤的受试者中T细胞应答或治疗受试者的实体瘤的方法，其中所述方法包括施用有效量的包含CAR的T细胞。在实施方案中，肿瘤与肾癌或肝癌相关。
本公开还涉及双特异性嵌合抗原受体(参见图26)、编码双特异性嵌合抗原受体的多核苷酸、和/或包含多核苷酸的修饰细胞，其中双特异性嵌合抗原受体包含第一抗原结合结构域、第二抗原结合结构域、胞质结构域和跨膜结构域，并且其中第一抗原结合结构域识别第一抗原，第二抗原结合结构域识别第二抗原。在实施方案中，第一抗原是与白细胞相关的抗原，第二抗原是实体瘤抗原。在实施方案中，第一抗原和第二抗原是相同或不同的。在实施方案中，第一抗原和第二抗原均是实体瘤抗原。例如，第一抗原是肿瘤相关的MUC1，第二抗原选自SEQ ID NO：1-22的抗原之一。在实施方案中，第一结合结构域和第二结合结构域通过接头(例如SEQ ID NO:188)连接。
在实施方案中，CAR的细胞内结构域包含共刺激信号传导结构区，所述共刺激信号传导结构区包括选自以下各项的共刺激分子的细胞内结构域：CD27、CD28、4-1BB、OX40、CD30、CD40、PD-1、ICOS、淋巴细胞功能相关抗原-1(LFA-1)、CD2、CD7、LIGHT、NKG2C、B7-H3及其任何组合。
在实施方案中，细胞内结构域包含CD3ζ信号传导结构域。实施方案涉及包含本文描述的分离的核酸序列的载体。实施方案涉及分离的细胞，所述分离的细胞包含本文描述的分离的核酸序列。
实施方案涉及包含细胞群的组合物，所述细胞群包括包含本文描述的CAR的T细胞。实施方案涉及由本文描述的分离的核酸序列编码的CAR。
本文描述的细胞(包括CAR细胞和修饰细胞)可以衍生自干细胞。干细胞可以是成人干细胞、胚胎干细胞、或非人类干细胞、脐带血干细胞、祖细胞、骨髓干细胞、诱导型多能干细胞、全能干细胞、或造血干细胞。细胞还可以是树突状细胞、NK细胞、B细胞或T细胞，所述T细胞选自炎性T淋巴细胞、细胞毒性T淋巴细胞、调节性T淋巴细胞和辅助性T淋巴细胞。在实施方案中，细胞可以衍生自CD4+T淋巴细胞和CD8+T淋巴细胞。在对本文描述的细胞进行扩增和基因修饰之前，可以通过各种非限制性方法从受试者中获得细胞来源。T细胞可以获自许多非限制性来源，包括外周血单核细胞、骨髓、淋巴结组织、脐带血、胸腺组织、来自感染部位的组织、腹水、胸腔积液、脾脏组织和肿瘤。在实施方案中，可以使用本领域技术人员可获得和已知的任何数量的T细胞系。在实施方案中，细胞可以衍生自健康供体、诊断患有癌症的患者或诊断患有感染的患者。在实施方案中，细胞是呈现不同表型特征的混合细胞群的一部分。
术语“干细胞”是指具有自我更新能力和分化成其他类型细胞能力的任何类型的细胞。例如，干细胞产生两个子干细胞(如在体外与胚胎干细胞培养时发生)或一个干细胞和经历分化的细胞(如在可产生血细胞的造血干细胞中发生)。不同类别的干细胞可以基于其来源和/或基于其分化成其他类型细胞的能力程度来加以区分。干细胞可以包括胚胎干(ES)细胞(即多能干细胞)、体干细胞、诱导型多能干细胞以及任何其他类型干细胞。
多能胚胎干细胞可存在于胚泡内细胞团中，具有较高的先天分化能力。例如，多能胚胎干细胞具有在体内形成任何类型细胞的潜力。当体外长时间生长时，ES保持多能性，子代细胞保留多向分化的潜力。
体干细胞可以包括胎儿干细胞(来自胎儿)和成年干细胞(存在于各种组织中，诸如骨髓)。这些细胞被认为具有低于多能ES细胞的分化能力，其中胎儿干细胞的能力大于成年干细胞的能力；它们显然仅分化成有限数量的不同类型细胞，并被描述为专能的(multipotent)。“组织特异性”干细胞通常仅产生一种类型的细胞。例如，胚胎干细胞可以分化成血液干细胞(例如，造血干细胞(HSC))，其可以进一步分化成各种血细胞(例如，红细胞、血小板、白细胞等)。
诱导型多能干细胞(iPS细胞或iPSC)可以包括通过诱导特定基因表达而人工衍生自非多能细胞(例如，成年体细胞)的一种多能干细胞。诱导型多能干细胞在许多方面类似于天然存在的多能干细胞(诸如胚胎干(ES)细胞)，所述方面诸如某些干细胞基因和蛋白质的表达、染色质甲基化模式、倍增时间、类胚体形成、畸胎瘤形成、可活嵌合体形成以及潜力和可分化性。诱导型多能细胞可以分离自成人胃、肝、皮肤细胞以及血细胞。
在实施方案中，CAR细胞、修饰细胞或细胞是T细胞、NK细胞、巨噬细胞或树突状细胞。例如，CAR细胞、修饰细胞或细胞是T细胞。
在实施方案中，抗原结合分子是T细胞受体(TCR)。在实施方案中，TCR是修饰TCR。在实施方案中，TCR衍生自患者体内自发产生的肿瘤特异性T细胞。在实施方案中，TCR结合肿瘤抗原。在实施方案中，肿瘤抗原包括CEA、gp100、MART-1、p53、MAGE-A3或NY-ESO-1。在实施方案中，TCR包括TCRγ和TCRδ链，或TCRα和TCRβ链。在实施方案中，可以分离T细胞克隆物，所述T细胞克隆物可表达对靶抗原具有高亲和力的TCR。在实施方案中，可以在多肽负载的抗原呈递细胞(APC)存在下培养肿瘤浸润淋巴细胞(TIL)或外周血单核细胞(PBMC)，所述多肽表示当存在于特定HLA等位基因背景下时已知可引起显性T细胞应答的表位。然后可以基于MHC-肽四聚体染色和/或识别和裂解靶细胞的能力来选择高亲和力克隆物，所述靶细胞用低滴定浓度的同源肽抗原负载。在选择克隆物后，通过分子克隆鉴定和分离TCRα和TCRβ链或TCRγ和TCRδ链。例如，对于TCRα和TCRβ链，然后使用TCRα和TCRβ基因序列来生成表达构建体，所述表达构建体可理想地促进人T细胞中两条TCR链的稳定、高水平表达。然后可生成转导媒介物(例如γ逆转录病毒或慢病毒)并测试其功能性(抗原特异性和功能亲合力)，将其用于产生大量的临床载体。等分试样的最终产品然后可用于转导靶T细胞群(通常从患者PBMC中纯化)，所述靶T细胞群在输注到受试者之前进行扩增。
在实施方案中，CAR的结合要素可以包括任何抗原结合部分，所述抗原结合部分在结合其同源抗原时可影响肿瘤细胞，例如杀死肿瘤细胞、抑制肿瘤细胞生长、或促进肿瘤细胞死亡。可以使用本领域已知的重组方法来获得编码所需分子的核酸序列，例如像通过从表达基因的细胞中筛选文库，通过从已知包括所述基因的载体中获得基因，或通过使用标准技术从包含所述基因的细胞和组织中直接分离来进行。或者，可以合成产生感兴趣的基因，而不是克隆。
本公开的实施方案还涉及其中插入本公开的DNA的载体。衍生自逆转录病毒(诸如慢病毒)的载体是实现长期基因转移的合适工具，因为它们允许转基因长期稳定地整合及其在子代细胞中繁殖。慢病毒载体与衍生自癌逆转录病毒(诸如鼠白血病病毒)的载体相比具有更多的优势，因为它们可以转导非增殖性细胞，诸如肝细胞。它们还具有低免疫原性的额外优势。
病毒可用于在体外和体内(在受试者中)将核酸递送到细胞中。可用于将核酸递送到细胞中的病毒的实例包括逆转录病毒、腺病毒、单纯疱疹病毒、牛痘病毒和腺相关病毒。
还存在用于将核酸递送到细胞中的非病毒方法，例如电穿孔、基因枪、声穿孔、磁转染以及使用寡核苷酸、脂复合物、树状聚合物和无机纳米颗粒。
编码CAR的天然或合成核酸的表达通常通过将编码CAR多肽或其部分的核酸可操作地连接到一种或多种启动子，并将构建体并入表达载体中来实现。载体可以适用于复制和整合到真核生物中。典型的克隆载体包含转录和翻译终止子、起始序列以及可用于调节所需核酸序列表达的启动子。
与编码CAR的合成核酸的表达和基因转移到哺乳动物细胞中相关的其他信息提供在美国专利号US8,906,682中，所述专利以引用的方式整体并入。
本公开的药物组合物可以适合于待治疗(或预防)的疾病的方式施用。施用的数量和频率将由诸如患者病状以及患者疾病的类型和严重性等因素来确定，尽管可以通过临床试验确定适当的剂量。
当指出“免疫学上有效的量”、“抗肿瘤有效的量”、“抑制肿瘤有效的量”或“治疗上有效的量”时，待施用的本公开的组合物的精确量可以由医师考虑患者(受试者)的年龄、体重、肿瘤大小、感染或转移程度以及病状的个体差异来确定。可以说，包含本文描述的T细胞的药物组合物可以在104至109个细胞/kg体重，优选105至106个细胞/kg体重的剂量下施用，包括所述范围内的所有整数值。T细胞组合物还可以在这些剂量下施用多次。可以通过使用免疫疗法中通常已知的输注技术来施用细胞(参见例如，Rosenberg等人,New Eng.J.ofMed.319:1676,1988)。通过监测患者的疾病征兆并相应地调整治疗，医学领域的技术人员可以容易地确定针对特定患者的最佳剂量和治疗方案。在实施方案中，可能需要向受试者施用激活的T细胞，随后抽血(或进行采血)，收集激活和扩增的T细胞，并向患者重新输注这些激活和扩增的T细胞。这个过程可以每几周进行多次。在实施方案中，可以从抽出的10cc至400cc的血液中激活T细胞。在实施方案中，从抽出的20cc、30cc、40cc、50cc、60cc、70cc、80cc、90cc或100cc的血液中激活T细胞。不受理论的束缚，使用这种多次抽血/多次再输注的方案可以选择出某些T细胞群。
本文描述的药物组合物的施用可以任何方便的方式进行，包括通过雾化吸入、注射、摄取、输注、植入或移植。本文描述的组合物可以皮下、皮内、肿瘤内、结节内、髓内、肌内、通过静脉内(i.v.)注射或或腹膜内向患者施用。在实施方案中，本公开的T细胞组合物通过皮内或皮下注射向患者施用。在实施方案中，本公开的T细胞组合物优选通过静脉内注射来施用。T细胞的组合物可以直接注射到肿瘤、淋巴结或感染部位。在本公开的实施方案中，结合任何数量的相关治疗方法(例如，在之前、同时或之后)，向患者施用细胞，所述细胞使用本文描述的方法或其中将T细胞扩增至治疗水平的本领域已知的其他方法进行激活和扩增，并且所述任何数量的相关治疗方法包括但不限于使用试剂的治疗，诸如抗病毒疗法、针对MS患者的西多福韦和白介素-2、阿糖孢苷(也称为ARA-C)或那他珠单抗治疗，或针对牛皮癣患者的依法珠单抗治疗或针对PML患者的其他治疗。在进一步的实施方案中，本公开的T细胞可与化学疗法、放射、免疫抑制剂(诸如环孢菌素、硫唑嘌呤、甲氨蝶呤、霉酚酸酯和FK506)、抗体或其他免疫消除剂(诸如CAM PATH)、抗CD3抗体或其他抗体疗法、细胞毒素、氟达立滨、环孢菌素、FK506、雷帕霉素、霉酚酸、类固醇、FR901228、细胞因子和辐照组合使用。这些药物抑制钙依赖性磷酸酶钙调磷酸酶(环孢素和FK506)或抑制对生长因子诱导的信号传导很重要的p70S6激酶(雷帕霉素)。(Liu等人,Cell 66:807-815,1991；Henderson等人,Immun 73:316-321,1991；Bierer等人,Curr.Opin.Immun 5:763-773,1993；Isoniemi(同上))。在实施方案中，将本公开的细胞组合物与骨髓移植、T细胞消融疗法(使用诸如氟达拉滨的化学治疗剂)、外部束放射疗法(XRT)、环磷酰胺或抗体(诸如OKT3或CAMPATH)结合(例如在之前、同时或之后)向患者施用。在实施方案中，本公开的细胞组合物在B细胞消融疗法(诸如与CD20反应的试剂，例如利妥昔单抗)之后施用。例如，受试者可以经历高剂量化学疗法的标准治疗，接着进行外周血干细胞移植。在实施方案中，在移植之后，受试者接受输注本公开的扩增免疫细胞。在实施方案中，在手术之前或之后施用扩增的细胞。
待向患者施用的上述治疗的剂量将随所治疗病状的确切性质和治疗接受者而变化。可以根据各种因素，由医师根据本领域公认的实践来进行用于人类施用的剂量缩放比例。
关于使用工程化或修饰的T细胞进行癌症治疗的方法的其他信息提供在美国专利号US8,906,682中，所述专利以引用的方式整体并入。
在实施方案中，本文描述的细胞群可用于自体CAR T细胞疗法。在实施方案中，CART细胞疗法是同种异体CAR T细胞疗法、TCR T细胞疗法和NK细胞疗法。
实施方案涉及用于制备修饰的细胞的体外方法。所述方法可以包括从受试者中获得细胞样品。例如，样品可以包括T细胞或T细胞祖细胞。所述方法可以还包括用编码至少CAR的DNA转染细胞，在选择性增强表达CAR的T细胞增殖的培养基中离体培养CAR细胞群。
在实施方案中，样品是冷冻保存的样品。在实施方案中，细胞样品来自脐带血，或细胞样品是来自受试者的外周血样品。在实施方案中，细胞样品通过单采或静脉穿刺获得。在实施方案中，细胞样品是T细胞亚群。
本公开的实施方案涉及使用嵌合抗原受体(CAR)细胞来治疗癌症，所述CAR细胞使用了与基因融合相关的分子。实施方案涉及编码嵌合抗原受体(CAR)的分离核酸序列，其中CAR包括细胞外结构域、跨膜结构域和细胞内结构域，其中细胞外结构域结合基因融合体的基因融合抗原。
如本文所用，术语“基因融合”是指将至少一部分基因融合到至少一部分其他基因。基因融合不需要包括整个基因或基因外显子。在一些例子中，基因融合与癌症改变相关。基因融合产物是指由基因融合产生的嵌合基因组DNA、嵌合信使RNA、截短蛋白或嵌合蛋白。基因融合产物可以通过美国专利9938582中描述的各种方法来检测，所述专利以引用的方式并入本文。“基因融合抗原”是指由基因融合产生的截短蛋白或嵌合蛋白。在实施方案中，基因融合抗原的表位可包括基因融合抗原的一部分或由基因融合引起的另一抗原的免疫原性部分。在实施方案中，基因融合抗原与细胞膜相互作用，或作为细胞膜的一部分。
在实施方案中，基因融合包括将至少一部分第一基因融合到至少一部分第二基因。在实施方案中，第一基因和第二基因包括表3中列出的融合体的第一基因和第二基因。在实施方案中，基因融合抗原与表3中列出的病状相关。
在实施方案中，可以使用诸如qPCR和FACS等实验方法进行人细胞中靶分子(列于表2中)的mRNA表达水平和蛋白表达水平的检测。此外，可以鉴定在相应肿瘤细胞中特异性表达的靶分子，所述靶分子在正常组织细胞中表达极低或无法检测到。
在实施方案中，可以进行体外杀伤测定以及与抗原阳性细胞共同培养的CAR T细胞的杀伤实验。与不表达相应抗原的对照细胞相比，CAR T细胞可表现出对相应抗原阳性细胞具有杀伤作用，与CAR T细胞共同培养的相应抗原阳性细胞数量减少，以及IFNγ、TNFα等的释放增加。
在实施方案中，可以进行体内杀伤测定。例如，可以向小鼠移植相应的致癌的抗原肿瘤细胞，并输注CAR T细胞，由此，有可能出现小鼠肿瘤减少，并且小鼠血液中可检测到IFNγ、TNFα以及其他信号。
实施方案涉及引发和/或增强患有实体瘤的受试者中T细胞应答或治疗受试者的实体瘤的方法，所述方法包括施用有效量的包含本文描述的CAR的T细胞。在实施方案中，CAR的细胞内结构域包含共刺激信号传导结构区，所述共刺激信号传导结构区包括选自以下各项的共刺激分子的细胞内结构域：CD27、CD28、4-1BB、OX40、CD30、CD40、PD-1、ICOS、淋巴细胞功能相关抗原-1(LFA-1)、CD2、CD7、LIGHT、NKG2C、B7-H3及其任何组合。在实施方案中，细胞内结构域包含CD3ζ信号传导结构域。
实施方案涉及包含本文描述的分离的核酸的载体。
实施方案涉及分离的细胞，所述分离的细胞包含本文描述的分离的核酸序列。实施方案涉及包含T细胞群的组合物，所述T细胞群包含本文描述的CAR。实施方案涉及由本文描述的分离的核酸序列编码的CAR。实施方案涉及引发和/或增强受试者中T细胞应答或治疗受试者肿瘤的方法，所述方法包括：施用有效量的包含本文描述的CAR的T细胞。
表3
Figure BDA0002948888430000151
Figure BDA0002948888430000161
Figure BDA0002948888430000171
Figure BDA0002948888430000181
Figure BDA0002948888430000191
Figure BDA0002948888430000201
在实施方案中，本文描述的CAR分子包含用于结合感兴趣抗原的一个或多个互补决定区(CDR)。CDR是用于结合特异性抗原的免疫球蛋白和T细胞受体中的可变结构域的一部分。每个可变结构域存在3个CDR。由于存在可变重结构域和可变轻结构域，因此存在6个用于结合抗原的CDR。此外，由于抗体具有两条重链和两条轻链，因此抗体总共具有12个用于结合抗原的CDR。在实施方案中，CAR分子包含以下各项中的一个或多个CDR：SIGLEC15、SLC6A3、KISS1R、QRFPR、GPR119、CLDN6、UPK2、ADAM12、SLC45A3、ACPP、MUC21、MUC16、MS4A12或ALPP。
本公开描述了修饰的细胞，所述修饰的细胞包括一个或多个不同的抗原结合结构域。修饰的细胞可以包括至少两种不同的抗原结合结构域：用于扩增和/或维持基因修饰细胞的第一抗原结合结构域，和用于杀死靶细胞(诸如肿瘤细胞)的第二抗原结合结构域。例如，第一抗原结合结构域结合表面标志物，诸如白细胞(WBC)的细胞表面分子(例如，CD19)，第二抗原结合结构域结合肿瘤细胞上的靶抗原。在实施方案中，细胞表面分子是WBC的表面抗原。在实施方案中，肿瘤细胞上的靶抗原包括以下各项中的一个或多个：SIGLEC15、SLC6A3、KISS1R、QRFPR、GPR119、CLDN6、UPK2、ADAM 12、SLC45A3、ACPP、MUC21、MUC16、MS4A12、或ALPP。至少两个抗原结合结构域可以位于同一或不同的修饰细胞上。例如，修饰的细胞可以包括包含结合CD19的CAR的修饰细胞、包含结合ACPP的CAR的修饰细胞、包含结合CD19和ACPP的CAR的修饰细胞、和/或包含分别结合CD19和ACPP的两个CAR的修饰细胞。在实施方案中，修饰的细胞可用于治疗患有癌症的受试者。
在实施方案中，本文描述的修饰细胞包括CAR分子，所述CAR分子包含至少两个不同的抗原结合结构域。CAR分子可以是双特异性CAR分子。例如，两个抗原结合结构域可以在同一CAR分子上，在不同CAR分子上、或在CAR分子和T细胞受体(TCR)上。单个CAR可以包括至少两个不同的抗原结合结构域，或两个不同的抗原结合结构域各自在单独的CAR分子上。至少两个不同的抗原结合结构域可以在同一CAR分子或不同CAR分子上，但在同一修饰细胞中。此外，至少两个不同的抗原结合结构域可以在同一修饰细胞中的CAR分子和T细胞受体上。在实施方案中，双特异性CAR分子可以包括结合WBC的抗原(例如，CD19)的结合结构域，以及结合实体瘤抗原的结合结构域。在实施方案中，双特异性CAR分子可以包括结合两种不同实体瘤抗原的两个结合结构域。
在实施方案中，至少两个不同的抗原结合结构域在不同的CAR分子上，所述CAR分子由不同的修饰细胞表达。此外，一个或多个不同的抗原结合结构域在CAR分子和T细胞受体上，所述CAR分子和T细胞受体由不同的修饰细胞表达。
相关序列提供在本申请和斯丹赛公司的PCT专利申请号：PCT/CN2016/075061、PCT/CN2018/088914和PCT/US19/013068中，所述申请以引用的方式整体并入。
通过参考以下示例性实施方案和实施例进一步描述本公开。提供这些示例性实施方案和实施例仅出于说明的目的，除非另有说明，否则它们不意图构成限制。因此，本公开决不应解释为限于以下示例性实施方案和实施例，而应解释为涵盖由于本文提供的教导而变得显而易见的任何和所有变型。
示例性实施方案
以下是示例性实施方案：
1、一种编码嵌合抗原受体(CAR)的分离核酸序列，其中CAR包括细胞外结构域、跨膜结构域和细胞内结构域，其中细胞外结构域结合实体瘤的抗原。
2、如实施方案1所述的分离核酸序列，其中细胞外结构域结合SIGLEC15。
3、如实施方案1所述的分离核酸序列，其中细胞外结构域结合SIGLEC15，所述SIGLEC15具有SEQ ID NO:17的氨基酸序列。
4、如实施方案1所述的分离核酸序列，其中细胞外结构域包含SEQ ID NOs:45-56的氨基酸序列之一。
5、一种引发和/或增强患有实体瘤的受试者中T细胞应答或治疗受试者的实体瘤的方法，所述方法包括施用有效量的包含实施方案2-4中任一项所述的CAR的T细胞。
6、如实施方案1-5中任一项所述的分离核酸序列或方法，其中肿瘤与尿路上皮癌相关。
7、如实施方案1所述的分离核酸序列，其中细胞外结构域结合KISS1R。
8、如实施方案1所述的分离核酸序列，其中细胞外结构域结合KISS1R，所述KISS1R具有SEQ ID NO:19的氨基酸序列。
9、如实施方案1所述的分离核酸序列，其中细胞外结构域包含SEQ ID NOs:71和72的氨基酸序列之一。
10、一种引发和/或增强患有实体瘤的受试者中T细胞应答或治疗受试者的实体瘤的方法，所述方法包括施用有效量的包含实施方案7-9中任一项所述的CAR的T细胞。
11、如实施方案1和7-10中任一项所述的分离核酸序列或方法，其中肿瘤与肾癌相关。
12、如实施方案1所述的分离核酸序列，其中细胞外结构域结合CLDN6。
13、如实施方案1所述的分离核酸序列，其中细胞外结构域结合CLDN6，所述CLDN6具有SEQ ID NO:22的氨基酸序列。
14、如实施方案1所述的分离核酸序列，其中细胞外结构域包含SEQ ID NOs:29-44的氨基酸序列之一。
15、一种引发和/或增强患有实体瘤的受试者中T细胞应答或治疗受试者的实体瘤的方法，所述方法包括施用有效量的包含实施方案12-15中任一项所述的CAR的T细胞。
16、如实施方案1和12-16中任一项所述的分离核酸序列或方法，其中肿瘤与子宫内膜癌和/或尿路上皮癌相关。
17、如实施方案1所述的分离核酸序列，其中细胞外结构域结合MUC16。
18、如实施方案1所述的分离核酸序列，其中细胞外结构域结合MUC16，所述MUC16具有SEQ ID NO:6的氨基酸序列。
19、如实施方案1所述的分离核酸序列，其中细胞外结构域包含SEQ ID NOs:63-70的氨基酸序列之一。
20、一种引发和/或增强患有实体瘤的受试者中T细胞应答或治疗受试者的实体瘤的方法，所述方法包括施用有效量的包含实施方案17-19中任一项所述的CAR的T细胞。
21、如实施方案1和17-20中任一项所述的分离核酸序列或方法，其中肿瘤与卵巢癌相关。
22、如实施方案1所述的分离核酸序列，其中细胞外结构域结合SLC6A3。
23、如实施方案1所述的分离核酸序列，其中细胞外结构域结合SLC6A3，所述SLC6A3具有SEQ ID NO:18的氨基酸序列。
24、一种引发和/或增强患有实体瘤的受试者中T细胞应答或治疗受试者的实体瘤的方法，所述方法包括施用有效量的包含实施方案22和23中任一项所述的CAR的T细胞。
25、如实施方案1和22-24中任一项所述的分离核酸序列或方法，其中肿瘤与肾癌相关。
26、如实施方案1所述的分离核酸序列，其中细胞外结构域结合QRFPR。
27、如实施方案1所述的分离核酸序列，其中细胞外结构域结合QRFPR，所述QRFPR具有SEQ ID NO:20的氨基酸序列。
28、一种引发和/或增强患有实体瘤的受试者中T细胞应答或治疗受试者的实体瘤的方法，所述方法包括施用有效量的包含实施方案26和27中任一项所述的CAR的T细胞。
29、如实施方案1和26-28中任一项所述的分离核酸序列或方法，其中肿瘤与肾癌相关。
30、如实施方案1所述的分离核酸序列，其中细胞外结构域结合GPR119。
31、如实施方案1所述的分离核酸序列，其中细胞外结构域结合GPR119，所述GPR119具有SEQ ID NO:21的氨基酸序列。
32、一种引发和/或增强患有实体瘤的受试者中T细胞应答或治疗受试者的实体瘤的方法，所述方法包括施用有效量的包含实施方案30和31中任一项所述的CAR的T细胞。
33、如实施方案1和30-32中任一项所述的分离核酸序列或方法，其中肿瘤与胰腺癌相关。
34、如实施方案1所述的分离核酸序列，其中细胞外结构域结合UPK2。
35、如实施方案1所述的分离核酸序列，其中细胞外结构域结合UPK2，所述UPK2具有SEQ ID NO:1的氨基酸序列。
36、一种引发和/或增强患有实体瘤的受试者中T细胞应答或治疗受试者的实体瘤的方法，所述方法包括施用有效量的包含实施方案34和35中任一项所述的CAR的T细胞。
37、如实施方案1和34-36中任一项所述的分离核酸序列或方法，其中肿瘤与尿路上皮癌和/或膀胱癌相关。
38、如实施方案1所述的分离核酸序列，其中细胞外结构域结合ADAM12。
39、如实施方案1所述的分离核酸序列，其中细胞外结构域结合ADAM12，所述ADAM12具有SEQ ID NO:2的氨基酸序列。
40、一种引发和/或增强患有实体瘤的受试者中T细胞应答或治疗受试者的实体瘤的方法，所述方法包括施用有效量的包含实施方案38和39中任一项所述的CAR的T细胞。
41、如实施方案1和38-40中任一项所述的分离核酸序列或方法，其中肿瘤与乳腺癌和/或胰腺癌相关。
42、如实施方案1所述的分离核酸序列，其中细胞外结构域结合SLC45A3。
43、如实施方案1所述的分离核酸序列，其中细胞外结构域结合SLC45A3，所述SLC45A3具有SEQ ID NO:3的氨基酸序列。
44、一种引发和/或增强患有实体瘤的受试者中T细胞应答或治疗受试者的实体瘤的方法，所述方法包括施用有效量的包含实施方案42和43中任一项所述的CAR的T细胞。
45、如实施方案1和42-44中任一项所述的分离核酸序列或方法，其中肿瘤与前列腺癌相关。
46、如实施方案1所述的分离核酸序列，其中细胞外结构域结合ACPP。
47、如实施方案1所述的分离核酸序列，其中细胞外结构域结合ACPP，所述ACPP具有SEQ ID NO:4的氨基酸序列。
48、一种引发和/或增强患有实体瘤的受试者中T细胞应答或治疗受试者的实体瘤的方法，所述方法包括施用有效量的包含实施方案46和47中任一项所述的CAR的T细胞。
49、如实施方案1和46-48中任一项所述的分离核酸序列或方法，其中肿瘤与前列腺癌相关。
50、如实施方案1所述的分离核酸序列，其中细胞外结构域结合MUC21。
51、如实施方案1所述的分离核酸序列，其中细胞外结构域结合MUC21，所述MUC21具有SEQ ID NO:5的氨基酸序列。
52、一种引发和/或增强患有实体瘤的受试者中T细胞应答或治疗受试者的实体瘤的方法，所述方法包括施用有效量的包含实施方案50和51中任一项所述的CAR的T细胞。
53、如实施方案1和50-52中任一项所述的分离核酸序列或方法，其中肿瘤与食管癌相关。
54、如实施方案1所述的分离核酸序列，其中细胞外结构域结合MS4A12。
55、如实施方案1所述的分离核酸序列，其中细胞外结构域结合MS4A12，所述MS4A12具有SEQ ID NO:7的氨基酸序列。
56、一种引发和/或增强患有实体瘤的受试者中T细胞应答或治疗受试者的实体瘤的方法，所述方法包括施用有效量的包含实施方案54和55中任一项所述的CAR的T细胞。
57、如实施方案1和54-56中任一项所述的分离核酸序列或方法，其中肿瘤与结肠直肠癌相关。
58、如实施方案1所述的分离核酸序列，其中细胞外结构域结合ALPP。
59、如实施方案1所述的分离核酸序列，其中细胞外结构域结合ALPP，所述ALPP具有SEQ ID NO:8的氨基酸序列。
60、一种引发和/或增强患有实体瘤的受试者中T细胞应答或治疗受试者的实体瘤的方法，所述方法包括施用有效量的包含实施方案58和59中任一项所述的CAR的T细胞。
61、如实施方案1和58-60中任一项所述的分离核酸序列或方法，其中肿瘤与子宫内膜癌相关。
62、如实施方案1所述的分离核酸序列，其中细胞外结构域结合SLC2A14。
63、如实施方案1所述的分离核酸序列，其中细胞外结构域结合SLC2A14，所述SLC2A14具有SEQ ID NO:9的氨基酸序列。
64、一种引发和/或增强患有实体瘤的受试者中T细胞应答或治疗受试者的实体瘤的方法，所述方法包括施用有效量的包含实施方案62和63中任一项所述的CAR的T细胞。
65、如实施方案1和62-64中任一项所述的分离核酸序列或方法，其中肿瘤与睾丸癌相关。
66、如实施方案1所述的分离核酸序列，其中细胞外结构域结合GS1-259H13.2。
67、如实施方案1所述的分离核酸序列，其中细胞外结构域结合GS1-259H13.2，所述GS1-259H13.2具有SEQ ID NO:10的氨基酸序列。
68、一种引发和/或增强患有实体瘤的受试者中T细胞应答或治疗受试者的实体瘤的方法，所述方法包括施用有效量的包含实施方案66和67中任一项所述的CAR的T细胞。
69、如实施方案1和66-69中任一项所述的分离核酸序列或方法，其中肿瘤与甲状腺癌或神经胶质瘤、或睾丸癌相关。
70、如实施方案1所述的分离核酸序列，其中细胞外结构域结合ERVFRD-1。
71、如实施方案1所述的分离核酸序列，其中细胞外结构域结合ERVFRD-1，所述ERVFRD-1具有SEQ ID NO:11的氨基酸序列。
72、一种引发和/或增强患有实体瘤的受试者中T细胞应答或治疗受试者的实体瘤的方法，所述方法包括施用有效量的包含实施方案70和71中任一项所述的CAR的T细胞。
73、如实施方案1和70-72中任一项所述的分离核酸序列或方法，其中肿瘤与肾癌或尿道癌相关。
74、如实施方案1所述的分离核酸序列，其中细胞外结构域结合ADGRG2。
75、如实施方案1所述的分离核酸序列，其中细胞外结构域结合ADGRG2，所述ADGRG2具有SEQ ID NO:12的氨基酸序列。
76、一种引发和/或增强患有实体瘤的受试者中T细胞应答或治疗受试者的实体瘤的方法，所述方法包括施用有效量的包含实施方案74和75中任一项所述的CAR的T细胞。
77、如实施方案1和74-76中任一项所述的分离核酸序列或方法，其中肿瘤与卵巢癌相关。
78、如实施方案1所述的分离核酸序列，其中细胞外结构域结合ECEL1。
79、如实施方案1所述的分离核酸序列，其中细胞外结构域结合ECEL1，所述ECEL1具有SEQ ID NO:13的氨基酸序列。
80、一种引发和/或增强患有实体瘤的受试者中T细胞应答或治疗受试者的实体瘤的方法，所述方法包括施用有效量的包含实施方案78和79中任一项所述的CAR的T细胞。
81、如实施方案1和78-80中任一项所述的分离核酸序列或方法，其中肿瘤与子宫内膜癌相关。
82、如实施方案1所述的分离核酸序列，其中细胞外结构域结合CHRNA2。
83、如实施方案1所述的分离核酸序列，其中细胞外结构域结合CHRNA2，所述CHRNA2具有SEQ ID NO:14的氨基酸序列。
84、一种引发和/或增强患有实体瘤的受试者中T细胞应答或治疗受试者的实体瘤的方法，所述方法包括施用有效量的包含实施方案82和83中任一项所述的CAR的T细胞。
85、如实施方案1和82-84中任一项所述的分离核酸序列或方法，其中肿瘤与前列腺癌相关。
86、如实施方案1所述的分离核酸序列，其中细胞外结构域结合GP2。
87、如实施方案1所述的分离核酸序列，其中细胞外结构域结合GP2，所述GP2具有SEQ ID NO:15的氨基酸序列。
88、一种引发和/或增强患有实体瘤的受试者中T细胞应答或治疗受试者的实体瘤的方法，所述方法包括施用有效量的包含实施方案86和87中任一项所述的CAR的T细胞。
89、如实施方案1和86-88中任一项所述的分离核酸序列或方法，其中肿瘤与胰腺癌相关。
90、如实施方案1所述的分离核酸序列，其中细胞外结构域结合PSG9。
91、如实施方案1所述的分离核酸序列，其中细胞外结构域结合PSG9，所述PSG9具有SEQ ID NO:16的氨基酸序列。
92、一种引发和/或增强患有实体瘤的受试者中T细胞应答或治疗受试者的实体瘤的方法，所述方法包括施用有效量的包含实施方案90和91中任一项所述的CAR的T细胞。
93、如实施方案1和90-92中任一项所述的分离核酸序列或方法，其中肿瘤与肾癌或肝癌相关。
94、如实施方案1-93中任一项所述的分离核酸序列或方法，其中细胞内结构域包含共刺激信号传导区，所述共刺激信号传导区包括选自以下的共刺激分子的细胞内结构域：CD27、CD28、4-1BB、OX40、CD30、CD40、PD-1、ICOS、淋巴细胞功能相关抗原-1(LFA-1)、CD2、CD7、LIGHT、NKG2C、B7-H3及其任何组合。
95、如实施方案1-93中任一项所述的分离核酸序列或方法，其中细胞内结构域包含CD3ζ信号传导结构域。
96、一种载体，其包含如实施方案1-93中任一项所述的分离核酸序列。
97、一种分离的细胞，其包含如实施方案1-93中任一项所述的分离核酸序列。
98、一种包含T细胞群的组合物，所述T细胞群包含如实施方案96或97中任一项所述的CAR。
99、一种CAR，其由实施方案1-93中任一项所述的分离核酸序列编码而得到。
100、一种编码嵌合抗原受体(CAR)的分离核酸序列，其中CAR包括细胞外结构域、跨膜结构域和细胞内结构域，其中细胞外结构域结合基因融合体的基因融合抗原。
101、如实施方案100所述的分离核酸序列，其中基因融合包括将至少一部分第一基因融合到至少一部分第二基因。
102、如实施方案101所述的分离核酸序列，其中第一基因和第二基因包括表5中列出的融合体的第一基因和第二基因。
103、如实施方案102所述的分离核酸序列，其中基因融合抗原与表3中列出的病状相关。
104、一种引发和/或增强患有实体瘤的受试者中T细胞应答或治疗受试者的实体瘤的方法，所述方法包括施用有效量的包含实施方案100-103中任一项所述的CAR的T细胞。
105、如实施方案100-103中任一项所述的分离核酸序列或方法，其中细胞内结构域包含共刺激信号传导区，所述共刺激信号传导区包括选自以下的共刺激分子的细胞内结构域：CD27、CD28、4-1BB、OX40、CD30、CD40、PD-1、ICOS、淋巴细胞功能相关抗原-1(LFA-1)、CD2、CD7、LIGHT、NKG2C、B7-H3及其任何组合。
106、如实施方案100-103中任一项所述的分离核酸序列或方法，其中细胞内结构域包含CD3ζ信号传导结构域。
107、一种载体，其包含如实施方案100-106中任一项所述的分离核酸序列。
108、一种分离的细胞，其包含如实施方案100-106中任一项所述的分离核酸序列。
109、一种包含T细胞群的组合物，所述T细胞群包含如实施方案8或9中任一项所述的CAR。
110、一种CAR，其由实施方案100-106中任一项所述的分离核酸序列编码而得到。
111、如实施方案1-110中任一项所述的分离核酸序列、修饰的T细胞或方法，其中细胞或修饰的细胞是衍生自健康供体或患癌受试者的T细胞，并且修饰的T细胞包含与免疫检查点抑制剂相关的显性阴性形式的受体。
112、如实施方案1-110中任一项所述的分离核酸序列、修饰的T细胞或方法，其中免疫检查点抑制剂选自以下：程序性死亡1(PD-1)、细胞毒性T淋巴细胞抗原-4(CTLA-4)、B淋巴细胞和T淋巴细胞弱化因子(BTLA)、T细胞免疫球蛋白粘蛋白-3(TIM-3)、淋巴细胞激活蛋白3(LAG-3)、具有Ig和ITIM结构域的T细胞免疫受体(TIGIT)、白细胞相关的免疫球蛋白样受体1(LAIR1)、自然杀伤细胞受体2B4(2B4)和CD 160。
113、如实施方案112所述的分离核酸序列、修饰的T细胞或方法，其中免疫检查点抑制剂是修饰的PD-1。
114、如实施方案112所述的分离核酸序列、修饰的T细胞或方法，其中修饰的PD-1缺乏用于PD-1信号转导的功能性PD-1细胞内结构域，干扰人细胞的人T细胞的PD-1与特定细胞的PD-L1之间的途径，包含或为PD-1细胞外结构域或PD-1跨膜结构域或其组合，或与野生型PD-1细胞内结构域相比包含取代或缺失的修饰的PD-1细胞内结构域，或包含或为可溶性受体，所述可溶性受体包含与特定细胞的PD-L1结合的PD-1细胞外结构域。
115、如实施方案112所述的分离核酸序列、修饰的T细胞或方法，其中与PD-L1对不包含编码修饰PD-1的至少一部分核酸序列的人T细胞的细胞因子产生的抑制作用相比，PD-L1对所述群体中人T细胞的细胞因子产生的抑制作用较小。
116、如实施方案1-104中任一项所述的分离核酸序列、修饰的T细胞或方法，其中修饰的T细胞被工程化以表达和分泌治疗剂，诸如细胞因子。
117、如实施方案116所述的分离核酸序列、修饰的T细胞或方法，其中治疗剂是或包括IFN-γ。
118、如实施方案116所述的分离核酸序列、修饰的T细胞或方法，其中治疗剂是或包括IL-6或IFN-γ、IL-17和CCL19中的至少一种。
119、如实施方案116所述的分离核酸序列、修饰的T细胞或方法，其中治疗剂是或包括IL-15或IL-12、或其组合。
120、如实施方案116所述的分离核酸序列、修饰的T细胞或方法，其中小蛋白或治疗剂是或包括重组或天然的细胞因子。
121、如实施方案116所述的分离核酸序列、修饰的T细胞或方法，其中治疗剂包括与小蛋白相关的FC融合蛋白。
122、如实施方案116所述的分离核酸序列、修饰的T细胞或方法，其中小蛋白是或包括IL-12、IL-15、IL-6或IFN-γ。
123、如实施方案116所述的分离核酸序列、修饰的T细胞或方法，其中治疗剂通过Hif1a、NFAT、FOXP3和/或NFkB来调节。
124、如实施方案116所述的分离核酸序列、修饰的T细胞或方法，其中小蛋白或治疗剂是或包括两种或更多种重组或天然的细胞因子，所述细胞因子通过2A或/IRES组分聚集。
125、如实施方案1-124中任一项所述的分离核酸序列、修饰的T细胞或方法，其中修饰的T细胞包括第一靶向载体和第二靶向载体，第一靶向载体包含编码结合血液抗原和治疗剂的CAR的核酸序列，第二靶向载体包含编码结合实体瘤抗原和显性阴性形式免疫检测点分子的CAR的核酸序列。
126、如实施方案1-124中任一项所述的分离核酸序列、修饰的T细胞或方法，其中修饰的T细胞包括第一靶向载体和第二靶向载体，第一靶向载体包含编码结合CD19和治疗剂的CAR的核酸序列，第二靶向载体包含编码结合UPK2、ACPP、SIGLEC15或KISS1R和显性阴性形式PD-1的CAR的核酸序列。
127、如实施方案1-124中任一项所述的分离核酸序列、修饰的T细胞或方法，其中修饰的T细胞包括第一靶向载体和第二靶向载体，第一靶向载体包含编码结合血液抗原的CAR的核酸序列，第二靶向载体包含编码结合实体瘤抗原的CAR的核酸序列。
128、如实施方案1-124中任一项所述的分离核酸序列、修饰的T细胞或方法，其中修饰的T细胞包括第一靶向载体和第二靶向载体，第一靶向载体包含编码结合B细胞抗原的CAR的核酸序列，第二靶向载体包含编码结合实体瘤抗原的CAR的核酸序列。
129、如实施方案128所述的分离核酸序列、修饰的T细胞或方法，其中实体瘤抗原是表2中列出的抗原中的至少一种，和/或B细胞抗原是CD19、CD20、CD22或BCMA。
130、如实施方案128所述的分离核酸序列、修饰的T细胞或方法，其中实体瘤抗原包括表2中列出的抗原中的至少一种。
131、一种引发和/或增强有需要的受试者中T细胞扩增的方法，所述方法包括向受试者施用有效量的实施方案130所述的T细胞组合物，所述受试者与施用有效量的不具有结合B细胞抗原的CAR的CAR T细胞的受试者相比，具有更高水平的T细胞扩增。
132、如实施方案1-131中任一项所述的分离核酸序列、修饰的T细胞或方法，其中修饰的T细胞包含编码hTERT、SV40LT、或其组合的核酸序列。
133、如实施方案132所述的分离核酸序列、修饰的T细胞或方法，其中修饰的T细胞比不具有核酸序列的T细胞更具有可增殖性。
134、如实施方案133所述的分离核酸序列、修饰的T细胞或方法，其中可增殖细胞保留正常T细胞/CAR T细胞的功能，诸如细胞治疗功能。
135、如实施方案133所述的分离核酸序列、修饰的T细胞或方法，其中T细胞包含CAR，并且在所述CAR的细胞外结构域识别的试剂存在下培养，因而产生修饰的CAR细胞。
136、如实施方案1-135中任一项所述的分离核酸序列、修饰的T细胞或方法，其中编码hTERT的核酸序列、编码SV40LT的核酸或其组合的整合包括编码hTERT的核酸序列、编码SV40LT的核酸或其组合的基因组整合和hTERT、SV40LT或其组合的组成型表达。
137、如实施方案1-136中任一项所述的分离核酸序列、修饰的T细胞或方法，其中hTERT、SV40LT或其组合的表达由诱导型表达系统诸如rtTA-TRE系统调节。
138、如实施方案1-136中任一项所述的分离核酸序列、修饰的T细胞或方法，其中修饰的T细胞包含编码自杀基因诸如HSV-TK系统的核酸序列。
139、如实施方案1-138中任一项所述的分离核酸序列、修饰的T细胞或方法，其中与原代人T细胞的移植物抗宿主疾病(GVHD)应答相比，所述细胞在生物不相容的人受体中的GVHD应答降低。
140、如实施方案1-138中任一项所述的分离核酸序列、修饰的T细胞或方法，其中细胞对内源性TRAC基因的表达减少。
141、一种结合ACPP的抗体，其中抗体包含重链可变区(HVR)序列和轻链可变区(LVR)序列，所述重链可变区序列包括SEQ ID NO:83、87、89或85的氨基酸序列，所述轻链可变区序列包括SEQ ID NO:82、86、88或84的氨基酸序列。
142、如实施方案141所述的抗体，其中LVR包括SEQ ID NO:82的氨基酸序列，HVR包括SEQ ID NO:83的氨基酸序列。
143、如实施方案141所述的抗体，其中LVR包括SEQ ID NO:86的氨基酸序列，HVR包括SEQ ID NO:87的氨基酸序列。
144、如实施方案141所述的抗体，其中LVR包括SEQ ID NO:88的氨基酸序列，HVR包括SEQ ID NO:89的氨基酸序列。
145、如实施方案141所述的抗体，其中LVR包括SEQ ID NO:84的氨基酸序列，HVR包括SEQ ID NO:85的氨基酸序列。
146、如实施方案141-145中任一项所述的抗体，其中抗体是包含LVR、接头和HVR的scFv。
147、如实施方案141-146中任一项所述的抗体，其中HVR被连接到人IgG链恒定区。
148、如实施方案147所述的抗体，其中人IgG为IgG1或IgG3。
149、如实施方案141-146中任一项所述的抗体，其中抗体被缀合到细胞毒性剂。
150、如实施方案141-146中任一项所述的抗体，其中细胞毒性剂是放射性同位素或毒素。
151、如实施方案141-146中任一项所述的抗体，其中抗体被缀合到衍生自4-1BB或CD28或其组合的序列上。
152、如实施方案141-146中任一项所述的抗体，其中抗体或片段在HEK293细胞中产生。
153、一种组合物，其包含实施方案141-152中任一项所述的抗体或片段以及药学上可接受的载体。
154、一种制品，其包括容器和包含在其中的组合物，其中组合物包含实施方案141-152中任一项所述的抗体或片段。
155、一种多核苷酸，其编码实施方案141-152中任一项所述的抗体或片段。
156、一种表达载体，其编码实施方案141-152中任一项所述的抗体或片段。
157、一种宿主细胞，其包含实施方案155和156中任一项所述的核酸。
158、一种治疗患癌受试者的方法，所述方法包括向受试者施用治疗有效量的实施方案141-152中任一项所述的抗体或片段。
159、一种治疗患有前列腺癌的受试者的方法，所述方法包括向受试者施用治疗有效量的实施方案141-152中任一项所述的抗体或片段。
160、一种修饰的细胞，其包含嵌合抗原受体(CAR)，所述CAR包含抗原识别结构域和细胞内结构域，所述抗原识别结构域包含实施方案141-152中任一项所述的抗体或片段。
161、一种治疗患癌受试者的方法，所述方法包括：向受试者施用修饰的细胞，其中修饰的细胞包含抗原识别结构域和细胞内结构域，所述抗原识别结构域包含实施方案141-152中任一项所述的抗体或片段。
162、如实施方案160和161中任一项所述的修饰细胞或方法，其中修饰的细胞包括以下各项中的至少一种：B细胞、T细胞、NK细胞、胚胎细胞、树突状细胞或巨噬细胞。
163、如实施方案162所述的方法，其中基因修饰的细胞在体内复制。
164、如实施方案161所述的方法，其中修饰的细胞在受试者中形成记忆细胞。
165、如实施方案161所述的方法，其中向受试者静脉内施用修饰的细胞。
166、如实施方案161所述的方法，其中修饰的细胞持续存在于受试者中。
167、如实施方案161所述的方法，其中修饰的细胞是自体T细胞。
168、一种修饰的细胞，其包含编码嵌合抗原受体(CAR)的核酸序列，其中CAR包含ACPP抗原结合结构域，所述ACPP抗原结合结构域包括SEQ ID NO:83和82、87和86、89和88、或85和84的氨基酸序列。
169、如实施方案168所述的修饰细胞，其中CAR还包含跨膜结构域、以及共刺激分子的细胞内结构域和信号传导结构域。
170、如实施方案169所述的修饰细胞，其中细胞内结构域包含CD3ζ信号传导结构域。
171、如实施方案169所述的修饰细胞，其中抗原结合片段是scFv。
172、如实施方案169所述的修饰细胞，其中scFv包含SEQ ID NO:83和82的氨基酸序列。
173、如实施方案169所述的修饰细胞，其中scFv包含SEQ ID NO:87和86的氨基酸序列。
174、如实施方案169所述的修饰细胞，其中scFv包含SEQ ID NO:89和88的氨基酸序列。
175、如实施方案169所述的人T细胞，其中scFv包含SEQ ID NO:85和84的氨基酸序列。
176、如实施方案167所述的修饰细胞，其中T细胞包含载体，所述载体包含核酸序列。
177、如实施方案176所述的修饰细胞，其中载体是慢病毒载体。
178、如实施方案168-177中任一项所述的修饰细胞，其中修饰的细胞包含其他CAR，所述其他CAR结合白细胞的抗原。
179、如实施方案178所述的修饰细胞，其中白细胞的抗原是B细胞抗原。
180、如实施方案179所述的修饰细胞，其中所述B细胞抗原的抗原是CD19、CD20、CD22或BCMA。
181、如实施方案168-180中任一项所述的修饰细胞，其中修饰的细胞包含显性阴性PD-1。
182、如实施方案168-180中任一项所述的修饰细胞，其中修饰的细胞包含缺乏功能性PD-1细胞内结构域的修饰PD-1。
183、如实施方案168-180中任一项所述的修饰细胞，其中细胞内结构域包含共刺激信号传导区，所述共刺激信号传导区包括选自以下各项的共刺激分子的细胞内结构域：CD27、CD28、4-1BB、OX40、CD30、CD40、PD-1、ICOS、淋巴细胞功能相关抗原-1(LFA-1)、CD2、CD7、LIGHT、NKG2C、B7-H3及其任何组合。
184、如实施方案183所述的修饰细胞，其中抗原是表皮生长因子受体(EGFR)、表皮生长因子受体的变体III(EGFRvIII)、人表皮生长因子受体2(HER2)、间皮素(MSLN)、前列腺特异性膜抗原(PSMA)、癌胚抗原(CEA)、双唾液酸神经节苷脂2(GD2)、白介素-13Ra2(IL13Rα2)、磷脂酰肌醇蛋白聚糖-3(GPC3)、碳酸酐酶IX(CAIX)、L1细胞粘附分子(L1-CAM)、癌症抗原125(CA125)、分化簇133(CD133)、成纤维细胞活化蛋白(FAP)、癌症/睾丸抗原1B(CTAG1B)、粘蛋白1(MUC1)、叶酸受体α(FR-α)、CD19、FZD10、TSHR、PRLR、Muc 17、GUCY2C、CD207、CD3、CD5、B细胞成熟抗原(BCMA)或CD4。
185、如实施方案168-184中任一项所述的修饰细胞，其中修饰的细胞是T细胞、NK细胞或树突状细胞。
186、如实施方案168-185中任一项所述的修饰细胞，其中修饰的细胞还包含编码治疗剂的核酸序列。
187、如实施方案186所述的修饰细胞，其中治疗剂以重组DNA构建体、mRNA或病毒载体形式存在于修饰的细胞中。
188、如实施方案186所述的修饰细胞，其中修饰的细胞包含编码治疗剂的治疗剂mRNA，所述mRNA并未整合到修饰细胞的基因组中。
189、如实施方案186所述的修饰细胞，其中修饰的细胞包含核酸序列或分离的核酸序列，所述核酸序列包含启动子，所述启动子包含用于转录调节剂的结合位点，所述转录调节剂调节治疗剂在细胞中的表达和/或分泌。
190、如实施方案189所述的修饰细胞，其中转录调节剂是或包括Hif1a、NFAT、FOXP3和/或NFkB。
191、如实施方案189所述的修饰细胞，其中启动子响应于转录调节剂。
192、如实施方案189所述的修饰细胞，其中启动子可操作地连接至编码治疗剂的核酸序列上，使得启动子驱动治疗剂在细胞中的表达和/或分泌。
193、一种药物组合物，其包含实施方案168-192中任一项所述的修饰细胞。
194、一种引发和/或增强有需要的受试者中T细胞应答和/或治疗受试者的肿瘤的方法，所述方法包括向受试者施用有效量的实施方案193所述的组合物。
195、一种结合UPK2的抗体或抗体片段，其中抗体或抗体片段包含重链可变区(HVR)序列和轻链可变区(LVR)序列，所述重链可变区序列包括SEQ ID NO:94、98、102、106、110、114、118或122的氨基酸序列，所述轻链可变区序列包括SEQ ID NO:93、97、101、105、109、113、117或121的氨基酸序列。
196、如实施方案195所述的抗体或抗体片段，其中LVR包括SEQ ID NO:93的氨基酸序列，HVR包括SEQ ID NO:94的氨基酸序列。
197、如实施方案195所述的抗体或抗体片段，其中LVR包括SEQ ID NO:97的氨基酸序列，HVR包括SEQ ID NO:98的氨基酸序列。
198、如实施方案195所述的抗体或抗体片段，其中LVR包括SEQ ID NO:101的氨基酸序列，HVR包括SEQ ID NO:102的氨基酸序列。
199、如实施方案195所述的抗体或抗体片段，其中LVR包括SEQ ID NO:105的氨基酸序列，HVR包括SEQ ID NO:106的氨基酸序列。
200、如实施方案195所述的抗体或抗体片段，其中LVR包括SEQ ID NO:109的氨基酸序列，HVR包括SEQ ID NO:110的氨基酸序列。
201、如实施方案195所述的抗体或抗体片段，其中LVR包括SEQ ID NO:113的氨基酸序列，HVR包括SEQ ID NO:114的氨基酸序列。
202、如实施方案195所述的抗体或抗体片段，其中LVR包括SEQ ID NO:117的氨基酸序列，HVR包括SEQ ID NO:118的氨基酸序列。
203、如实施方案195所述的抗体或抗体片段，其中LVR包括SEQ ID NO:121的氨基酸序列，HVR包括SEQ ID NO:122的氨基酸序列。
204、如实施方案195-203中任一项所述的抗体或抗体片段，其中HVR被连接到人IgG链恒定区。
205、如实施方案204所述的抗体或抗体片段，其中人IgG为IgG1或IgG3。
206、如实施方案195-205中任一项所述的抗体或抗体片段，其中抗体或抗体片段被缀合到细胞毒性剂。
207、如实施方案12中所述的抗体或抗体片段，其中细胞毒性剂是放射性同位素或毒素。
208、如实施方案195-207中任一项所述的抗体或抗体片段，其中抗体或抗体片段被缀合到衍生自4-1BB或CD28或其组合的序列上。
209、如实施方案195-208中任一项所述的抗体或抗体片段，其中抗体或片段在HEK293细胞中产生。
210、如实施方案195-209中任一项所述的抗体或抗体片段，其中抗体是scFv。
211、如实施方案210所述的抗体或抗体片段，其中scFv包括或为SEQ ID NO:92、96、100、104、108、112、116或120。
212、如实施方案210所述的抗体或抗体片段，其中抗体或抗体片段包括SEQ IDNO:92、96、100、104、108、112、116或120。
213、一种组合物，其包含实施方案195-212中任一项所述的抗体或片段以及药学上可接受的载体。
214、一种制品，其包括容器和包含在其中的组合物，其中组合物包含实施方案195-212中任一项所述的抗体或片段。
215、一种多核苷酸，其编码实施方案195-212中任一项所述的抗体或片段。
216、一种表达载体，其编码实施方案195-212中任一项所述的抗体或片段。
217、一种宿主细胞，其包含实施方案21或216中任一项所述的核酸。
218、一种治疗患有UPK2阳性肿瘤(例如，尿路上皮癌和膀胱癌)的受试者的方法，所述方法包括向受试者施用治疗有效量的实施方案195-212中任一项所述的抗体或片段。
219、一种治疗患有尿路上皮癌和膀胱癌的受试者的方法，所述方法包括向受试者施用治疗有效量的实施方案195-212中任一项所述的抗体或片段。
220、一种嵌合抗原受体(CAR)，所述CAR包含抗原结合结构域，所述抗原结合结构域包含实施方案195-212中任一项所述的抗体或片段。
221、一种多核苷酸，其编码实施方案220所述的CAR。
222、一种修饰的细胞，其包含编码嵌合抗原受体(CAR)的核酸序列，其中CAR包含UPK2抗原结合结构域，所述UPK2抗原结合结构域包括实施方案195-212中任一项所述的抗体或片段。
223、如实施方案222所述的修饰细胞，其中CAR还包含跨膜结构域、以及共刺激分子的细胞内结构域和信号传导结构域。
224、如实施方案223所述的修饰细胞，其中细胞内结构域包含CD3ζ信号传导结构域。
225、如实施方案222-224中任一项所述的修饰细胞，其中抗原结合片段是scFv。
226、如实施方案222-224中任一项所述的修饰细胞，其中scFv包含SEQ ID NO:92、96、100、104、108、112、116或120的氨基酸序列。
227、如实施方案222-224中任一项所述的修饰细胞，其中修饰的细胞包含载体，所述载体包含核酸序列，所述核酸序列包括SEQ ID NO:91、95、99、103、107、111、115或119。
228、如实施方案227所述的修饰细胞，其中载体是慢病毒载体。
229、根据实施方案222-228中任一项所述的修饰细胞，其中修饰的细胞是衍生自原代人T细胞的T细胞，所述原代人T细胞从患者中分离得到。
230、根据实施方案222-228中任一项所述的修饰细胞，其中修饰的细胞是衍生自原代人T细胞的T细胞，所述原代人T细胞从人供体中分离得到。
231、如实施方案229所述的修饰细胞，其中细胞对内源性TRAC基因的表达减少。
232、如实施方案222-231中任一项所述的修饰细胞，其中修饰的细胞包含其他CAR，所述其他CAR结合白细胞的抗原。
233、如实施方案232所述的修饰细胞，其中白细胞的抗原是B细胞抗原。
234、如权利要求233所述的修饰细胞，其中所述B细胞抗原的抗原是CD19、CD20、CD22或BCMA。
235、如实施方案222-234中任一项所述的修饰细胞，其中修饰的细胞包含显性阴性PD-1。
236、如实施方案222-234中任一项所述的修饰细胞，其中修饰的细胞包含缺乏功能性PD-1细胞内结构域的修饰PD-1。
237、如实施方案222-234中任一项所述的修饰细胞，其中细胞内结构域包含共刺激信号传导区，所述共刺激信号传导区包括选自以下各项的共刺激分子的细胞内结构域：CD27、CD28、4-1BB、OX40、CD30、CD40、PD-1、ICOS、淋巴细胞功能相关抗原-1(LFA-1)、CD2、CD7、LIGHT、NKG2C、B7-H3及其任何组合。
238、如实施方案237所述的修饰细胞，其中抗原是表皮生长因子受体(EGFR)、表皮生长因子受体的变体III(EGFRvIII)、人表皮生长因子受体2(HER2)、间皮素(MSLN)、前列腺特异性膜抗原(PSMA)、癌胚抗原(CEA)、双唾液酸神经节苷脂2(GD2)、白介素-13Ra2(IL13Rα2)、磷脂酰肌醇蛋白聚糖-3(GPC3)、碳酸酐酶IX(CAIX)、L1细胞粘附分子(L1-CAM)、癌症抗原125(CA125)、分化簇133(CD133)、成纤维细胞活化蛋白(FAP)、癌症/睾丸抗原1B(CTAG1B)、粘蛋白1(MUC1)、叶酸受体α(FR-α)、CD19、FZD10、TSHR、PRLR、Muc 17、GUCY2C、CD207、CD3、CD5、B细胞成熟抗原(BCMA)或CD4。
239、如实施方案222-238中任一项所述的修饰细胞，其中修饰的细胞是T细胞、NK细胞或树突状细胞。
240、如实施方案222-239中任一项所述的修饰细胞，其中修饰的细胞还包含编码治疗剂的核酸序列。
241、如实施方案240所述的修饰细胞，其中治疗剂以重组DNA构建体、mRNA或病毒载体形式存在于修饰的细胞中。
242、如实施方案240所述的修饰细胞，其中修饰的细胞包含编码治疗剂的治疗剂mRNA，所述mRNA并未整合到修饰细胞的基因组中。
243、如实施方案240所述的修饰细胞，其中修饰的细胞包含核酸序列或分离的核酸序列，所述核酸序列包含启动子，所述启动子包含用于转录调节剂的结合位点，所述转录调节剂调节治疗剂在细胞中的表达和/或分泌。
244、如实施方案243所述的修饰细胞，其中转录调节剂是或包括Hif1a、NFAT、FOXP3和/或NFkB。
245、如实施方案243所述的修饰细胞，其中启动子响应于转录调节剂。
246、如实施方案243所述的修饰细胞，其中启动子可操作地连接至编码治疗剂的核酸序列上，使得启动子驱动治疗剂在细胞中的表达和/或分泌。
247、一种药物组合物，其包含实施方案222-246中任一项所述的修饰细胞。
248、一种引发和/或增强有需要的受试者中T细胞应答和/或治疗受试者的肿瘤的方法，所述方法包括向受试者施用有效量的实施方案247所述的组合物。
249、一种编码结合分子的分离核酸序列，所述结合分子包含第一结构域和第二结合结构域，其中第一结合结构域结合抗原，第二结合结构域结合T细胞CD3受体复合体。
250、如实施方案249所述的分离核酸，其中抗原是表皮生长因子受体(EGFR)、表皮生长因子受体的变体III(EGFRvIII)、人表皮生长因子受体2(HER2)、间皮素(MSLN)、前列腺特异性膜抗原(PSMA)、癌胚抗原(CEA)、双唾液酸神经节苷脂2(GD2)、白介素-13Ra2(IL13Rα2)、磷脂酰肌醇蛋白聚糖-3(GPC3)、碳酸酐酶IX(CAIX)、L1细胞粘附分子(L1-CAM)、癌症抗原125(CA125)、分化簇133(CD133)、成纤维细胞活化蛋白(FAP)、癌症/睾丸抗原1B(CTAG1B)、粘蛋白1(MUC1)、叶酸受体α(FR-α)、CD19、FZD10、TSHR、PRLR、Muc 17、GUCY2C、CD207、CD3、CD5、B细胞成熟抗原(BCMA)或CD4。
251、如实施方案249所述的分离核酸序列，其中第二结合结构域结合CD3ε，和/或第一结合结构域包括SEQ ID NO:30、34、38、42、46、64、68、92、96、100、104、108、112、116、120和136-172的氨基酸序列之一。
252、如实施方案249所述的分离核酸序列，其中第一结合结构域结合tn-Muc1、TSHR、FZD10、PRLR、Muc 16、Muc 17、GUCY2C、CD207、CLDN18.2、CLDN6或SIGL1C。
253、如实施方案249所述的分离核酸序列，其中分离核酸序列编码包含SEQ IDNO:123-135的氨基酸序列之一的多肽。
254、一种载体，其包含实施方案249-253中任一项所定义的核酸序列。
255、一种宿主细胞，其用实施方案1-5中任一项所定义的核酸序列或用实施方案254所定义的载体进行转化或转染。
256、一种用于产生实施方案1至4中任一项所述的结合分子的方法，所述方法包括在允许表达实施方案1-4中任一项所定义的结合分子的条件下培养实施方案254中定义的宿主细胞，以及从培养物中回收所产生的结合分子。
257、一种药物组合物，其包含实施方案1至4中任一项所述的结合分子或根据实施方案256所述的方法产生的结合分子。
258、一种试剂盒，其包含实施方案1至4中任一项所定义的结合分子、实施方案1-4中任一项所定义的核酸分子、实施方案253中所定义的载体和/或实施方案7中所定义的宿主细胞。
259、一种用于治疗或改善疾病的方法，所述方法包括向有需要的受试者施用实施方案1至4中任一项所述的结合分子，或实施方案256所述的方法。
260、如实施方案259所述的方法，还包括：向有需要的受试者施用有效量的T细胞，所述T细胞包含结合白细胞的细胞表面分子的抗原结合分子，其中白细胞的细胞表面分子是CD19、CD22、CD20、BCMA、CD5、CD7、CD2、CD16、CD56、CD30、CD14、CD68、CD11b、CD18、CD169、CD1c、CD33、CD38、CD138或CD13。
261如实施方案260所述的方法，其中抗原结合分子包含抗原结合结构域、跨膜结构域、共刺激结构域和CD3ζ信号传导结构域。
262、如实施方案261所述的方法，其中T细胞具有结合抗原的其他CAR。
263、一种编码嵌合抗原受体(CAR)的分离核酸序列，其中CAR包括细胞外结构域、跨膜结构域和细胞内结构域，细胞外结构域包含至少两个结合肿瘤抗原的结合结构域。
264、如实施方案263所述的分离核酸序列，其中至少两个结合结构域是分别结合ta-Muc1和非ta-Muc1抗原的scFv。
265、如实施方案263所述的分离核酸序列，其中至少两个结合结构域包括结合ta-Muc1的抗原结合结构域和结合不同于ta-Muc1的抗原的其他抗原结合结构域。
266、如实施方案265所述的分离核酸序列，其中不同于ta-Muc1的抗原是表皮生长因子受体(EGFR)、表皮生长因子受体的变体III(EGFRvIII)、人表皮生长因子受体2(HER2)、间皮素(MSLN)、前列腺特异性膜抗原(PSMA)、癌胚抗原(CEA)、双唾液酸神经节苷脂2(GD2)、白介素-13Ra2(IL13Rα2)、磷脂酰肌醇蛋白聚糖-3(GPC3)、碳酸酐酶IX(CAIX)、L1细胞粘附分子(L1-CAM)、癌症抗原125(CA125)、分化簇133(CD133)、成纤维细胞活化蛋白(FAP)、癌症/睾丸抗原1B(CTAG1B)、叶酸受体α(FR-α)、CD19、FZD10、TSHR、PRLR、Muc 17、GUCY2C、CD207、CD3、CD5、B细胞成熟抗原(BCMA)或CD4。
267、如实施方案263所述的分离核酸序列，其中细胞内结构域包含共刺激信号传导区，所述共刺激信号传导区包括选自以下的共刺激分子的细胞内结构域：CD27、CD28、4-1BB、OX40、CD30、CD40、PD-1、ICOS、淋巴细胞功能相关抗原-1(LFA-1)、CD2、CD7、LIGHT、NKG2C、B7-H3及其任何组合。
268、如实施方案263所述的分离核酸序列，其中至少两个结合结构域包括SEQ IDNO：135和SEQ ID NO：30、34、38、42、46、64、68、92、96、100、104、108、112、116、120和136-172之一。
269、如实施方案15所述的分离核酸序列，其中至少两个结合结构域包括SEQ IDNO:70和SEQ ID NO:59-84之一。
270、一种CAR细胞群，其包含实施方案249-253和263-268中任一项所述的分离核酸序列。
271、一种药物组合物，其包含实施方案270所述的CAR细胞群。
272、一种引发和/或增强有需要的受试者中T细胞应答、引发或引起有需要的受试者中T细胞应答和/或治疗受试者的肿瘤的方法，所述方法包括向受试者施用有效量的实施方案271所述的组合物。
273、一种或多种修饰的细胞，其包括两个或更多个不同的抗原结合结构域，其中至少第一抗原结合结构域结合细胞表面标志物，第二抗原结合结构域结合肿瘤抗原。
274、如实施方案273所述的一种或多种修饰的细胞，其中细胞表面标志物包括白细胞的细胞表面标志物。
275、如实施方案273或274所述的一种或多种修饰的细胞，其中肿瘤抗原包括以下各项中的一个或多个：SIGLEC15、SLC6A3、KISS1R、QRFPR、GPR119、CLDN6、UPK2、ADAM12、SLC45A3、ACPP、MUC21、MUC16、MS4A12或ALPP。
276、如实施方案273-275中任一项所述的一种或多种修饰的细胞，其中抗原结合结构域在同一CAR分子上，在不同CAR分子上，或在CAR分子和T细胞受体上。
277、如实施方案273-276中任一项所述的一种或多种修饰的细胞，其中两个或更多个不同的抗原结合结构域在不同修饰分子的不同CAR分子上。
278、如实施方案273-277中任一项所述的一种或多种修饰的细胞，其中两个或更多个不同的抗原结合结构域在不同修饰分子的CAR分子和T细胞受体上。
279、一种细胞群，其包含实施方案273-278中任一项所述的一种或多种修饰的细胞。
280、如实施方案1-279中任一项所述的核酸序列、CAR分子、抗体、载体、细胞、细胞群、组合物、药物组合物、试剂盒或方法在通过疗法治疗受试者身体的方法中的用途。
281、如实施方案280所述的用途，其中受试者是人或动物。
282、如实施方案280或281所述的用途，其中受试者正患有癌症。
283、如实施方案280-282中任一项所述的用途，其中用途会引发和/或增强受试者中T细胞应答。
284、如实施方案1-279中任一项所述的核酸序列、CAR分子、抗体、载体、细胞、细胞群、组合物、药物组合物、试剂盒或方法在引发和/或增强受试者中T细胞应答的方法中的用途。
285、如实施方案284所述的用途，其中受试者是人或动物。
286、如实施方案284或285所述的用途，其中受试者正患有癌症。
实施例
通过参考以下实施例进一步描述本公开。提供这些实施例仅出于说明的目的，除非另有说明，否则它们不意图构成限制。因此，本公开绝不应被解释为限于以下实施例，而应被解释为涵盖由于本文提供的教导而变得显而易见的任何和所有变型。
CAR在T细胞上的表达
生成编码CAR的慢病毒载体(参见Chimeric Receptors Containing CD137Signal Transduction Domains Mediate Enhanced Survival of T Cells andIncreased Antileukemic Efficacy,In Vivo Molecular Therapy，第17卷第8期，1453–1464，2009年8月，所述参考文献以引用的方式并入本文)，并且将其引入到人T细胞中。
从患者中获得原代T细胞。用慢病毒载体转导所获得的原代T细胞以获得修饰的T细胞。进行流式细胞术并分析以确定CAR在原代T细胞中的表达(图2)。与细胞培养、慢病毒载体构建和流式细胞术相关的技术可在Control of large,established tumorxenografts with genetically retargeted human T cells containing CD28 andCD137 domains.3360–3365PNAS 2009年3月3日，第106卷第9期中找到，所述参考文献以引用的方式并入本文。
抗原表达和相关肿瘤分析
使用诸如qPCR和FACS等实验方法进行人细胞中靶分子的mRNA表达水平和蛋白表达水平的检测。已表明以下列出的一些靶分子在相应的肿瘤细胞中特异性表达，在正常组织中具有相对较低的表达或无法检测的表达。例如，八种基因位于正常组织中，并在肿瘤细胞中过表达。靶点和肿瘤之间的相应关系提供在表4中。进行各种测定(例如，杀伤)，结果在图3-7中示出。与细胞培养、细胞毒性T淋巴细胞测定构建相关的技术可在“Control oflarge,established tumor xenografts with genetically retargeted human T cellscontaining CD28 and CD137 domains”,PNAS 2009年3月3日，第106卷第9期，3360-3365中找到，所述参考文献以引用的方式整体并入本文。
表4
Figure BDA0002948888430000301
Figure BDA0002948888430000311
鉴定基因融合抗原
分析数据库(例如，TCGA)以鉴定基因融合产物和基因融合抗原。鉴定出数百种基因融合产物，并确定它们与癌症相关。在这些数百种基因融合产物中，基于预先确定的标准进一步鉴定出33个基因融合抗原组。例如，发现这些基因融合产物可在肿瘤细胞中表达，并且融合基因的融合蛋白位于胞质膜中。这33个基因融合抗原组的信息列于表5中。与表5中每一行对应的样品包括TCGA-D8-A1XJ-01A-11R-A14M-07、TCGA-E2-A574-01A-11R-A29R-07、TCGA-FU-A3TX-01A-11R-A22U-07、TCGA-CV-7434-01A-11R-2132-07、TCGA-G7-6793-01A-11R-1965-07、TCGA-DB-5277-01A-01R-1470-07、TCGA-KT-A7W1-01A-11R-A34F-07、TCGA-VM-A8CD-01A-11R-A36H-07、TCGA-DD-A3A5-01A-11R-A22L-07、TCGA-DD-AAEA-01A-11R-A41C-07、TCGA-ZS-A9CF-01A-11R-A38B-07、TCGA-44-7670-01A-11R-2066-07、TCGA-55-7281-01A-11R-2039-07、TCGA-62-8394-01A-11R-2326-07、TCGA-78-7143-01A-11R-2039-07、TCGA-78-7146-01A-11R-2039-07、TCGA-46-6025-01A-11R-1820-07、TCGA-85-7710-01A-11R-2125-07、TCGA-O2-A52V-01A-31R-A262-07、TCGA-FB-AAPZ-01A-11R-A41B-07、TCGA-P8-A5KC-01A-11R-A35K-07、TCGA-WB-A81D-01A-11R-A35L-07、TCGA-EJ-5510-01A-01R-1580-07、TCGA-EJ-A46G-01A-31R-A26U-07、TCGA-ZG-A9L2-01A-31R-A41O-07、TCGA-ZG-A9L2-01A-31R-A41O-07、TCGA-EI-7002-01A-11R-1928-07、TCGA-DX-A1KZ-01A-11R-A24X-07、TCGA-DX-A2J0-01A-11R-A21T-07、TCGA-DX-A3UF-01A-11R-A30C-07、TCGA-DX-AB2V-01A-11R-A41I-07、TCGA-K1-A6RU-01A-11R-A32Q-07和TCGA-EB-A24D-01A-11R-A18T-07，其各自代表TCGA数据库中的一个条形码。TCGA条形码代表TCGA数据库中参与者及其样品的元数据。
表5
Figure BDA0002948888430000312
Figure BDA0002948888430000321
Figure BDA0002948888430000331
Figure BDA0002948888430000341
Figure BDA0002948888430000351
Figure BDA0002948888430000361
表6：标识物和相关序列
Figure BDA0002948888430000362
Figure BDA0002948888430000371
抗SINGLEC-15 CAR和抗KISSR CAR
图2示出表达CAR的T细胞的流式细胞分析。在第1天，对CD3阳性T细胞进行分选。在第3天，用编码CAR的慢病毒感染T细胞(感染复数(MOI)：50:1)。在第5-6天，进行表达测定。在第6天，用3T3-抗原-mcherry-SC以30:1的比率培养T细胞。序列和相应参考号列于图2-7和表7中。
图3示出抗SIGLEC15 CAR(SIGLEC15-CAR SEQ ID NO:46、50、51和52)杀伤测定的结果。可以观察到，抗SIGLEC15 CAR T细胞杀死了基质细胞。单独阴性对照SIGLEC15组是不具有添加的抗SIGLEC15 CAR T细胞的组，NT组属于非转染T细胞。图4和图5示出与基质细胞共培养的抗SIGLEC15 CAR的细胞因子释放测定结果。
表7
Figure BDA0002948888430000381
图6示出抗KISSR CAR(KISSR-CAR：SEQ ID NO:71)的杀伤测定结果。可以观察到，抗KISS1R CAR T细胞杀死了基质细胞。NT组加入非转染T细胞。图7示出与基质细胞共培养的抗KISSR CAR T细胞的细胞因子释放测定结果。
ACPP抗体制备和抗ACPP CAR
图8-10示出ACPP抗体的流式细胞术测定。用pcDNA-ACPP-flag质粒转染293T细胞以表达C末端带有flag标签的ACPP蛋白。2天后，使用7种ACPP抗体和flag标签抗体染色来检测染色。ACPP单一染色不会破坏膜染色，首先添加ACPP一抗，然后使用山羊抗人FITC二抗。当单一染色flag标记时，使用APC直接标记的一抗，并且将膜染色。当破裂时，进行Flag/ACPP双重染色。Flag标签抗体检测到26.39％的表达抗原的细胞。S5D1抗体检测到30.35％的表达ACPP抗原的细胞。双重染色结果表明阳性细胞具有相同的ACPP和flag表达水平。染色结果是特异性的。S5F2的结合力较弱，其余抗体流均无信号。转染质粒能够表达在293T细胞上表达C末端带有flag标签的ACPP跨膜蛋白。流式细胞术实验表明ACPP抗体S5D1与细胞膜上表达的抗原具有良好的结合能力。Flag标记证实了蛋白质的正常表达。
针对图10中的亲和力测定，使用GE公司的BIAcore X-100生物分子相互作用分析仪对两种单克隆抗体S5D1和S5F2的亲和力进行分析。使用常规程序进行亲和力分析。使用涂覆在芯片上的抗人抗体捕获人单克隆抗体S5D1或S5F2。然后使用不同浓度的重组表达的PAP作为流动相进行亲和力分析。单克隆抗体S5D1的亲和力约为9nM。推测S5F2的亲和力低于100nM。S5D1对ACPP抗原具有更高的亲和力。抗体的序列列于表6中。
通过克隆和表达所选血清前列腺酸磷酸酶(PAP)抗原，并使用噬菌体展示人抗体库(人噬菌体展示)的制备PAP抗原进行筛选，可生成ACPP抗体。将ACPP基因序列克隆到重组抗原表达载体PTSE-His中。将构建的重组质粒转染到HEK293细胞中。使用GE公司的HistrapFF亲和色谱柱来纯化重组蛋白。参考经典的固相筛选策略，使用ACPP-His作为抗原筛选人单链抗体库。单链抗体库由完全合成的人单链抗体、天然人单链抗体和半合成-半天然单链抗体库等总共12个子文库组成。文库总容量超过109，正确率约为75％。使用固相包被的抗原进行三轮常规筛选。在第二轮筛选之后和在第三轮筛选之后，随机选择600个单克隆克隆物(1200个单克隆克隆物)进行单克隆鉴定。获得约40种能够特异性结合PAP的阳性单克隆物。对所有单克隆物进行序列分析。结果表明这些阳性克隆物共有7种不同的抗体序列。代表性克隆物分别是S4C7、S5D1、S5F2、S9F5、S10E12、S12D4和S12D9(序列列于表6中)。将上述七种scFv的重链可变区和轻链可变区的基因分别克隆到真核表达载体pTSEG1n和pTSEK中。使用HEK293细胞瞬时表达系统来制备七种人类全抗体。使用蛋白质A亲和色谱柱纯化重组表达的全抗体。
图11示出前列腺癌石蜡切片的免疫荧光染色。相应方法包括：1.组织脱水；2.组织透明；3.浸蜡；4.嵌入；5.切开和烘烤切开物；6.切片和脱蜡；7.抗原回收；8.血清封闭；9.添加一抗；10.添加荧光二抗；11.血清遮光封闭；12.添加一抗；13.添加荧光二抗；14.复合染料核；15.收集图像。如所示出，原位前列腺癌和与原位癌瘤相邻的组织具有较高的ACPP表达。同时，用于染色的ACPP抗体是S5D1，从而表明该抗体可特异性识别ACPP。选择S5D1进行以下的进一步实验。肿瘤组织切片中的ACPP表达可以通过免疫荧光染色来可视化，并且也可以反映抗体的特异性和敏感性。
图12示出表达ACPP的293T细胞。在第0天，将293-WT(293-野生型)细胞消化并放置在6孔板上。在第1天，用ACPP-慢病毒表达载体感染细胞。在第2天，更换培养基以去除慢病毒，并加入新鲜培养基。将细胞消化并通过流式细胞术进行分析。用于流式细胞术的抗体是S5D1，并且抗体用量为1μg/100μl。流式细胞分析结果表明293T-ACPP细胞的ACPP表达为97.80％。所述293T-ACPP细胞在后续实验中可被用作ACPP阳性细胞。ACPP可以在293T细胞中过表达，所述293T细胞可以作为用于评估ACPP CAR T细胞功能实验的ACPP阳性细胞。
图13示出表达抗ACPP CAR的T细胞(抗ACPP scFv：SEQ ID:173)的流式细胞术测定。在第0天，从健康志愿者身上抽取外周血；分选CD3+T细胞；以及以1:1比率加入CD3/CD28Dynabeads免疫磁珠。在第1天，用载体转导T细胞。根据MOI＝13的感染率获得CD19CAR T细胞；根据MOI＝130的感染率获得ACPP CAR T细胞。在第2天，更换培养基，去除慢病毒。然后使用新鲜培养基将细胞重新悬浮。
在第6天，使用流式细胞术来检测CAR表达。由于CD19CAR和ACPP CAR都包含人源化抗体，因此将人CAR抗体用于检测。结果是，CD19 CAR在感染的T细胞中的表达为59.55％，ACPP CAR在感染的T细胞中的表达为26.16％。由于CD19CAR和ACPP CAR都是人源化抗体，因此通过使用人类CAR抗体进行流式细胞检测来测量CAR表达。
图14示出共培养测定的结果。用NT细胞对ACPP CAR T细胞与CD19CAR T细胞的CAR比率进行归一化。将104个CAR+细胞和104个293T-WT或293T-ACPP或Nalm-6细胞进行共培养。48小时后，通过流式细胞术检测CAR阳性CD8阳性细胞的CD137表达。左列是与293T-WT细胞共培养的CAR T细胞的CD137表达，在CD19CAR组和ACPP CAR组中均不存在CD137表达。这表明由于293T中不存在特异性抗原表达，因此CAR T细胞无法激活。在中间一列中，将CAR T细胞与过量表达ACPP的293T或293T-ACPP细胞共培养。ACPP CAR组中CD137的表达为27.15％，而在CD19CAR组中CD137不表达。这表明ACPP-CAR T细胞由ACPP识别并激活。右列是CAR T细胞与Nalm-6细胞的共培养，所述Nalm-6细胞是由CD19CAR T细胞特异性识别并激活的CD19阳性细胞。结果表明，CD19CAR组中CD137的表达为21.01％，而在ACPP CAR组中CD137不表达。结果符合预期。综上所述，证明了ACPP CAR T细胞可特异性识别并可由ACPP抗原激活。CD137是用于T细胞激活的标志蛋白，因此与CAR T细胞和基质靶细胞共培养后，CAR T细胞的CD137上调水平可用于确定CAR T细胞是否被激活。
图15示出响应于ACPP的抗ACPP CAR T细胞的IFN-γ释放。用NT细胞对ACPP CAR T细胞与CD19CAR T细胞的CAR比率进行归一化。通过将0.2×104个或104个CAR+细胞和104个293T-WT或293T-ACPP或Nalm-6细胞共培养来进行实验。24小时后，收集上清液并检查所释放的IFN-γ量。Nalm-6是CD19阳性细胞，293T-ACPP是过表达ACPP的293T细胞。图15是示出CAR T细胞:基质细胞为1:1的结果的图。当与293T-ACPP共培养时，ACPP CAR T细胞表现出显著的IFN-γ释放，从而表明293T-ACPP可以被ACPP CAR T细胞识别并释放IFN-γ杀死靶细胞。同时，Nalm-6也可以被CD19CAR T细胞识别并释放IFN-γ杀死靶细胞。此外，Nalm-6不会刺激ACPP CAR T细胞释放IFN-γ。CD19 CAR T细胞也不能刺激293T-ACPP释放IFN-γ。总之，ACPP CAR T细胞可以特异性识别ACPP阳性靶细胞，并在其刺激下释放IFN-γ杀死靶细胞。在T细胞杀死靶细胞的过程中，通常会释放大量的细胞因子(诸如IFN-γ)以增强杀伤能力。因此，可以通过CAR T细胞与基质靶细胞共培养时所释放的IFN-γ量来确定CAR T细胞是否具有杀死靶细胞的能力。
图16示出抗ACPP CAR在T细胞上的CAR表达可以通过检测人CAR抗体来测量。在第0天，从健康志愿者身上抽取外周血；分选CD3+T细胞；以及以1:1比率加入CD3/CD28Dynabeads免疫磁珠。在第1天，用载体转导T细胞。根据MOI＝1的感染率获得CD19CAR T细胞；根据MOI＝50的感染率获得ACPP CAR T细胞。在第2天，更换培养基，去除慢病毒。然后使用新鲜培养基将细胞重新悬浮。在第6天，使用流式细胞术来检测CAR表达。由于CD19CAR和ACPP CAR都是人源化抗体，因此将人CAR抗体用于检测。结果示于图中。CD19CAR在CD19CART细胞中的表达为50.64％，ACPP在ACPP CAR T细胞(6501)中的表达为37.2％，在ACPP CART细胞(6503)中的表达为33.93％，并且在ACPP CAR T细胞(6504)中的表达为45.63％。由于19CAR和ACPP CAR都是人源化抗体，因此可以通过使用人类CAR抗体进行流式细胞检测来获得CAR表达水平。
图17示出响应于ACPP的抗ACPP CAR T细胞的细胞因子释放。用NT细胞对ACPP CART细胞与CD19 CAR T细胞的CAR比率进行归一化。通过将0.2x104或1x104个CAR+细胞与1x104个293T-ACPP或Nalm-6细胞共培养来进行实验，24小时后收集上清液以检测IFN-γ和IL2。Nalm-6是CD19阳性细胞，293T-ACPP是过表达ACPP的293T细胞。图17示出与293T-ACPP共培养时，ACPP CAR T 6503表现出显著增加的IFN-γ和IL2释放，从而表明ACPP CAR T 6503细胞识别293T-ACPP并激活IFN-γ和IL2释放。相比之下，ACPP CAR T 6501和6504细胞不能激活IFN-γ和IL2释放。同时，CD19CAR T细胞能够识别Nalm-6并激活IFN-γ和IL2释放。此外，Nalm-6不能激活ACPP CAR T细胞释放IFN-γ。同时，293T-ACPP不能激活CD19CAR T细胞释放IFN-γ。这表明两种靶向的CAR T细胞是特异性的。在T细胞杀死靶细胞的过程中，通常会释放大量的细胞因子(诸如IFN-γ和IL2)以增强杀伤能力。因此，可以通过CAR T细胞与基质靶细胞共培养时IFN-γ和IL2的释放量来确定CAR T细胞是否具有杀死靶细胞的能力。
图18和图19示出不同条件下的CD137表达。CAR 1204是人源CD19CAR，其可以用人CAR抗体和CD137抗体标记。用NT细胞对ACPP CAR T细胞与CD19CAR T细胞的CAR比率进行归一化。将104个CAR+细胞与104个293T-ACPP或Nalm-6细胞共培养，并在24小时后通过流式细胞术检测CD8阳性细胞的CD137表达。第一行是CAR T细胞和293T-ACPP共培养的结果。293T-ACPP未激活CD19CAR T细胞表达CD137。293T-ACPP激活ACPP CAR T 6503细胞表达CD137。293T-ACPP未激活ACPP CART 6501和6504细胞表达CD137。第二行是CAR T细胞和CD19阳性细胞系Nalm6共培养的结果。Nalm6可以激活CD19CAR T细胞表达CD137。Nalm6不能激活所有的ACPP CAR T细胞表达CD137，这表明CD19CAR T和ACPP CAR T细胞是特异性的。CD137是用于T细胞激活的标志蛋白。因此，通过在CAR T细胞和基质靶细胞共培养之后检测CAR T细胞中的CD137表达来确定CAR T细胞被激活。
UPK2抗体制备
使用大肠杆菌表达系统制备重组UPK2细胞外结构域(UPK2-His)。取6-8周龄的BALB/c小鼠，并在免疫之前对小鼠进行尾静脉采血，留下背景血清。首次免疫UPK2-His重组抗原，并用弗氏完全佐剂乳化。每只小鼠腹膜内注射50μg重组抗原。每两周加强一次免疫，UPK2-His重组抗原通过不完全佐剂乳化。针对三次加强免疫，每只小鼠腹膜内注射50μg重组抗原。在第三次加强免疫之前进行尾静脉采血，分析血清UPK2抗体效价。结果表明在四只小鼠中有三只小鼠血清中的UPK2抗体效价达到106或更高(图20)，从而表明免疫成功。
改变第五次免疫以冲击免疫，并且使用不含佐剂的UPK2-His重组抗原作为免疫原。每只小鼠腹膜内注射50μg重组抗原，并在免疫3天后处死小鼠。从小鼠中收集脾细胞，并在图20所示的图中标记为“左前”。
使用小鼠淋巴细胞分离液(Dakko，CAT#DKW33-R0100)分离小鼠脾淋巴细胞，并使用总RNA提取试剂盒(Tiangen，CAT#DP430)对分离的淋巴细胞进行总计。RNA提取。使用提取的总RNA为模板，将第一链cDNA合成试剂盒(Thermo科学，CAT#K1621)用来分别合成重链可变区和轻链可变区。逆转录引物是基因特异性引物，并进行引物配对。这些区域分别位于抗体重链恒定区和抗体轻链恒定区，并且特异性序列分别是PmCGR：TGCATTTGAACTCCTTGCC(SEQ ID NO:189)和PmCKR：CCATCAATCTTCCACTTGAC(SEQ ID NO:190)。将合成的cDNA立即保存在-70℃下进行储存。然后，通过逆转录获得cDNA并将其用作模板来获得引物(Journalof Immunological Methods,201(1997),35-55)，并且通过PCR分别扩增鼠抗体VH和VK。使用重叠延伸PCR技术来构建单链抗体(scFv)。最后，将制备的小鼠单链抗体基因克隆到载体pADSCFV-S中以构建ScFv文库。该抗体文库的文库容量达到1.6x108，正确率为41.5％。
使用重组UPK2-his作为抗原，参照经典固相筛选策略筛选小鼠单链抗体文库，并在第二轮中，通过结合、洗脱、中和、感染和扩增进行三轮筛选。在第三轮筛选之后，通过噬菌体ELISA鉴定约700个单克隆克隆物。选择60个具有高阳性ELISA信号的克隆进行序列分析，以获得8种具有与UPK2-His结合的不同序列的菌株。八种抗体是：克隆S2B7、S2E2、S3A4、S3C10、S3D10、S7F9、S7F11和S7G7(图21)。八种单克隆抗体的重链和轻链可变区序列(scFv)示于表6中。
将上述8个scFv的重链和轻链可变区基因分别克隆到真核表达载体pTSEG1n和pTSEK中，并使用该公司的HEK293细胞瞬时表达系统制备8种鼠-人嵌合抗体(鼠抗体可变区)。人抗体恒定区)。重组全抗体通过蛋白质A亲和色谱柱纯化，并且通过SDS-PAGE显示。这八种抗体正常表达，其纯度达到蛋白质鉴定的水平。
使用经典的ELISA方法分析重组全抗体结合抗原UPK2-His的能力。结果示于图22中。如图22所示，所有8种抗体可以结合抗原UPK2-His。
同时，通过类似的ELISA方法分析所制备的单克隆抗体的特异性。如图23所示，这8种重组抗体可以特异性识别重组UPK2-His，并且各种无关抗原中不存在明显的非特异性结合。
使用GE公司的BIAcore X-100分析8种单克隆抗体的亲和力。使用常规程序进行亲和力分析，具体的方法是首先用包被在芯片上的抗人抗体捕获人单克隆抗体，然后使用不同浓度的重组UPK2-His作为流动相进行亲和力分析。如表8所示，这些重组抗体的亲和力(KD)通常在0.1nM与10nM之间。其中，S7F11/S7G7的结合和解离较慢，而S3D10的结合太慢。当通过BIAcore X-100分析这三种单克隆抗体进行亲和力分析时，KD的自动拟合较差，数据仅供参考。
表8：通过BIAcore确定的重组抗UPK2单克隆抗体亲和力参数
单克隆抗体 Kon Koff KD 备注
S2B7 1.493x10<sup>5</sup> 3.495x10<sup>-3</sup> 2.34x10<sup>8</sup>
S3A4 1.125x10<sup>5</sup> 3.05x10<sup>-3</sup> 2.712x10<sup>-8</sup>
S7F9 1.4x10<sup>5</sup> 2.344x10<sup>-3</sup> 1.674x10<sup>-8</sup>
S2E2 1.381x10<sup>6</sup> 3.894x10<sup>-3</sup> 2.82x10<sup>-9</sup>
S3C10 1.226x10<sup>6</sup> 1.117x10<sup>-3</sup> 9.109x10<sup>-10</sup>
S7F11 3.504x10<sup>3</sup> 8.126x10<sup>-6</sup> 2.319x10<sup>-9</sup> Kd超出
S7G7 5.049x10<sup>4</sup> 1.202x10<sup>-6</sup> 2.381x10<sup>-11</sup> Kd超出
S3D10 6.431x10<sup>2</sup> 2.614x10<sup>-3</sup> 4.064x10<sup>-6</sup> U值＝15
在本研究中，使用重组UPK2细胞外域(UPK2-His)来完成小鼠的免疫，鼠免疫文库的构建、筛选和单克隆鉴定。获得八种鼠单克隆抗体(S2B7、S2E2、S3A4、S3C10、S3D10、S7F9、S7F11和S7G7)，其具有不同的序列并能够结合重组UPK2，并且初步的特异性分析表明，这些单克隆抗体特异性结合重组UPK2-his。基于BIAcore的亲和力分析表明，这些重组抗UPK2抗体的亲和力通常在0.1nM与10nM之间。
本说明书中引用的所有出版物、专利和专利申请均以引用的方式整体并入本文，就好像每个单独的出版物、专利或专利申请被明确地并单独地指示以引用的方式并入。尽管已根据各种实施方案描述了前述内容，但是本领域技术人员将理解，可以在不脱离其精神的情况下进行各种修改、替换、省略和改变。
序列表
<110> 上海斯丹赛生物技术有限公司
美国斯丹赛生物技术公司（INNOVATIVE CELLULAR THERAPEUTICS, INC）
<120> 用于治疗实体瘤的嵌合抗原受体细胞
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<150> 62731079
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<150> 62807482
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Cys Cys Pro Cys Arg Ala Arg Leu Ala Phe Arg Asn Leu Gly Ala Leu
245 250 255
Leu Pro Arg Leu His Gln Leu Cys Cys Arg Met Pro Arg Thr Leu Arg
260 265 270
Arg Leu Phe Val Ala Glu Leu Cys Ser Trp Met Ala Leu Met Thr Phe
275 280 285
Thr Leu Phe Tyr Thr Asp Phe Val Gly Glu Gly Leu Tyr Gln Gly Val
290 295 300
Pro Arg Ala Glu Pro Gly Thr Glu Ala Arg Arg His Tyr Asp Glu Gly
305 310 315 320
Val Arg Met Gly Ser Leu Gly Leu Phe Leu Gln Cys Ala Ile Ser Leu
325 330 335
Val Phe Ser Leu Val Met Asp Arg Leu Val Gln Arg Phe Gly Thr Arg
340 345 350
Ala Val Tyr Leu Ala Ser Val Ala Ala Phe Pro Val Ala Ala Gly Ala
355 360 365
Thr Cys Leu Ser His Ser Val Ala Val Val Thr Ala Ser Ala Ala Leu
370 375 380
Thr Gly Phe Thr Phe Ser Ala Leu Gln Ile Leu Pro Tyr Thr Leu Ala
385 390 395 400
Ser Leu Tyr His Arg Glu Lys Gln Val Phe Leu Pro Lys Tyr Arg Gly
405 410 415
Asp Thr Gly Gly Ala Ser Ser Glu Asp Ser Leu Met Thr Ser Phe Leu
420 425 430
Pro Gly Pro Lys Pro Gly Ala Pro Phe Pro Asn Gly His Val Gly Ala
435 440 445
Gly Gly Ser Gly Leu Leu Pro Pro Pro Pro Ala Leu Cys Gly Ala Ser
450 455 460
Ala Cys Asp Val Ser Val Arg Val Val Val Gly Glu Pro Thr Glu Ala
465 470 475 480
Arg Val Val Pro Gly Arg Gly Ile Cys Leu Asp Leu Ala Ile Leu Asp
485 490 495
Ser Ala Phe Leu Leu Ser Gln Val Ala Pro Ser Leu Phe Met Gly Ser
500 505 510
Ile Val Gln Leu Ser Gln Ser Val Thr Ala Tyr Met Val Ser Ala Ala
515 520 525
Gly Leu Gly Leu Val Ala Ile Tyr Phe Ala Thr Gln Val Val Phe Asp
530 535 540
Lys Ser Asp Leu Ala Lys Tyr Ser Ala
545 550
<210> 4
<211> 418
<212> PRT
<213> 智人（Homo sapiens）
<400> 4
Met Arg Ala Ala Pro Leu Leu Leu Ala Arg Ala Ala Ser Leu Ser Leu
1 5 10 15
Gly Phe Leu Phe Leu Leu Phe Phe Trp Leu Asp Arg Ser Val Leu Ala
20 25 30
Lys Glu Leu Lys Phe Val Thr Leu Val Phe Arg His Gly Asp Arg Ser
35 40 45
Pro Ile Asp Thr Phe Pro Thr Asp Pro Ile Lys Glu Ser Ser Trp Pro
50 55 60
Gln Gly Phe Gly Gln Leu Thr Gln Leu Gly Met Glu Gln His Tyr Glu
65 70 75 80
Leu Gly Glu Tyr Ile Arg Lys Arg Tyr Arg Lys Phe Leu Asn Glu Ser
85 90 95
Tyr Lys His Glu Gln Val Tyr Ile Arg Ser Thr Asp Val Asp Arg Thr
100 105 110
Leu Met Ser Ala Met Thr Asn Leu Ala Ala Leu Phe Pro Pro Glu Gly
115 120 125
Val Ser Ile Trp Asn Pro Ile Leu Leu Trp Gln Pro Ile Pro Val His
130 135 140
Thr Val Pro Leu Ser Glu Asp Gln Leu Leu Tyr Leu Pro Phe Arg Asn
145 150 155 160
Cys Pro Arg Phe Gln Glu Leu Glu Ser Glu Thr Leu Lys Ser Glu Glu
165 170 175
Phe Gln Lys Arg Leu His Pro Tyr Lys Asp Phe Ile Ala Thr Leu Gly
180 185 190
Lys Leu Ser Gly Leu His Gly Gln Asp Leu Phe Gly Ile Trp Ser Lys
195 200 205
Val Tyr Asp Pro Leu Tyr Cys Glu Ser Val His Asn Phe Thr Leu Pro
210 215 220
Ser Trp Ala Thr Glu Asp Thr Met Thr Lys Leu Arg Glu Leu Ser Glu
225 230 235 240
Leu Ser Leu Leu Ser Leu Tyr Gly Ile His Lys Gln Lys Glu Lys Ser
245 250 255
Arg Leu Gln Gly Gly Val Leu Val Asn Glu Ile Leu Asn His Met Lys
260 265 270
Arg Ala Thr Gln Ile Pro Ser Tyr Lys Lys Leu Ile Met Tyr Ser Ala
275 280 285
His Asp Thr Thr Val Ser Gly Leu Gln Met Ala Leu Asp Val Tyr Asn
290 295 300
Gly Leu Leu Pro Pro Tyr Ala Ser Cys His Leu Thr Glu Leu Tyr Phe
305 310 315 320
Glu Lys Gly Glu Tyr Phe Val Glu Met Tyr Tyr Arg Asn Glu Thr Gln
325 330 335
His Glu Pro Tyr Pro Leu Met Leu Pro Gly Cys Ser Pro Ser Cys Pro
340 345 350
Leu Glu Arg Phe Ala Glu Leu Val Gly Pro Val Ile Pro Gln Asp Trp
355 360 365
Ser Thr Glu Cys Met Thr Thr Asn Ser His Gln Val Leu Lys Val Ile
370 375 380
Phe Ala Val Ala Phe Cys Leu Ile Ser Ala Val Leu Met Val Leu Leu
385 390 395 400
Phe Ile His Ile Arg Arg Gly Leu Cys Trp Gln Arg Glu Ser Tyr Gly
405 410 415
Asn Ile
<210> 5
<211> 560
<212> PRT
<213> 智人（Homo sapiens）
<400> 5
Met Lys Met Gln Lys Gly Asn Val Leu Leu Met Phe Gly Leu Leu Leu
1 5 10 15
His Leu Glu Ala Ala Thr Asn Ser Asn Glu Thr Ser Thr Ser Ala Asn
20 25 30
Thr Gly Ser Ser Val Ile Ser Ser Gly Ala Ser Thr Ala Thr Asn Ser
35 40 45
Gly Ser Ser Val Thr Ser Ser Gly Val Ser Thr Ala Thr Ile Ser Gly
50 55 60
Ser Ser Val Thr Ser Asn Gly Val Ser Ile Val Thr Asn Ser Glu Phe
65 70 75 80
His Thr Thr Ser Ser Gly Ile Ser Thr Ala Thr Asn Ser Glu Phe Ser
85 90 95
Thr Val Ser Ser Gly Ile Ser Ile Ala Thr Asn Ser Glu Ser Ser Thr
100 105 110
Thr Ser Ser Gly Ala Ser Thr Ala Thr Asn Ser Glu Ser Ser Thr Pro
115 120 125
Ser Ser Gly Ala Ser Thr Ala Thr Asn Ser Asp Ser Ser Thr Thr Ser
130 135 140
Ser Gly Ala Ser Thr Ala Thr Asn Ser Asp Ser Ser Thr Thr Ser Ser
145 150 155 160
Glu Ala Ser Thr Ala Thr Asn Ser Glu Ser Ser Thr Thr Ser Ser Gly
165 170 175
Ala Ser Thr Ala Thr Asn Ser Glu Ser Ser Thr Val Ser Ser Arg Ala
180 185 190
Ser Thr Ala Thr Asn Ser Glu Ser Ser Thr Thr Ser Ser Gly Ala Ser
195 200 205
Thr Ala Thr Asn Ser Glu Ser Arg Thr Thr Ser Asn Gly Ala Gly Thr
210 215 220
Ala Thr Asn Ser Glu Ser Ser Thr Thr Ser Ser Gly Ala Ser Thr Ala
225 230 235 240
Thr Asn Ser Glu Ser Ser Thr Pro Ser Ser Gly Ala Gly Thr Ala Thr
245 250 255
Asn Ser Glu Ser Ser Thr Thr Ser Ser Gly Ala Gly Thr Ala Thr Asn
260 265 270
Ser Glu Ser Ser Thr Val Ser Ser Gly Ile Ser Thr Val Thr Asn Ser
275 280 285
Glu Ser Ser Thr Pro Ser Ser Gly Ala Asn Thr Ala Thr Asn Ser Glu
290 295 300
Ser Ser Thr Thr Ser Ser Gly Ala Asn Thr Ala Thr Asn Ser Asp Ser
305 310 315 320
Ser Thr Thr Ser Ser Gly Ala Ser Thr Ala Thr Asn Ser Glu Ser Ser
325 330 335
Thr Thr Ser Ser Gly Ala Ser Thr Ala Thr Asn Ser Glu Ser Ser Thr
340 345 350
Thr Ser Ser Gly Ala Ser Thr Ala Thr Asn Ser Gly Ser Ser Thr Thr
355 360 365
Ser Ser Gly Thr Ser Thr Ala Thr Asn Ser Glu Ser Ser Thr Val Ser
370 375 380
Ser Gly Ala Ser Thr Ala Thr Thr Ser Glu Ser Ser Thr Thr Ser Ser
385 390 395 400
Gly Ala Ser Thr Ala Thr Asn Ser Glu Ser Ser Thr Val Ser Ser Gly
405 410 415
Ala Ser Thr Ala Thr Asn Ser Glu Ser Ser Thr Thr Ser Ser Gly Ala
420 425 430
Asn Thr Ala Thr Asn Ser Gly Ser Ser Val Thr Ser Ala Gly Ser Gly
435 440 445
Thr Ala Ala Leu Thr Gly Met His Thr Thr Ser His Ser Ala Ser Thr
450 455 460
Ala Val Ser Glu Ala Lys Pro Gly Gly Ser Leu Val Pro Trp Glu Ile
465 470 475 480
Phe Leu Ile Thr Leu Val Ser Val Val Ala Ala Val Gly Leu Phe Ala
485 490 495
Gly Leu Phe Phe Cys Val Arg Asn Ser Leu Ser Leu Arg Asn Thr Phe
500 505 510
Asn Thr Ala Val Tyr His Pro His Gly Leu Asn His Gly Leu Gly Pro
515 520 525
Gly Pro Gly Gly Asn His Gly Ala Pro His Arg Pro Arg Trp Ser Pro
530 535 540
Asn Trp Phe Trp Arg Arg Pro Val Ser Ser Ile Ala Met Glu Met Ser
545 550 555 560
<210> 6
<211> 14507
<212> PRT
<213> 智人（Homo sapiens）
<400> 6
Met Leu Lys Pro Ser Gly Leu Pro Gly Ser Ser Ser Pro Thr Arg Ser
1 5 10 15
Leu Met Thr Gly Ser Arg Ser Thr Lys Ala Thr Pro Glu Met Asp Ser
20 25 30
Gly Leu Thr Gly Ala Thr Leu Ser Pro Lys Thr Ser Thr Gly Ala Ile
35 40 45
Val Val Thr Glu His Thr Leu Pro Phe Thr Ser Pro Asp Lys Thr Leu
50 55 60
Ala Ser Pro Thr Ser Ser Val Val Gly Arg Thr Thr Gln Ser Leu Gly
65 70 75 80
Val Met Ser Ser Ala Leu Pro Glu Ser Thr Ser Arg Gly Met Thr His
85 90 95
Ser Glu Gln Arg Thr Ser Pro Ser Leu Ser Pro Gln Val Asn Gly Thr
100 105 110
Pro Ser Arg Asn Tyr Pro Ala Thr Ser Met Val Ser Gly Leu Ser Ser
115 120 125
Pro Arg Thr Arg Thr Ser Ser Thr Glu Gly Asn Phe Thr Lys Glu Ala
130 135 140
Ser Thr Tyr Thr Leu Thr Val Glu Thr Thr Ser Gly Pro Val Thr Glu
145 150 155 160
Lys Tyr Thr Val Pro Thr Glu Thr Ser Thr Thr Glu Gly Asp Ser Thr
165 170 175
Glu Thr Pro Trp Asp Thr Arg Tyr Ile Pro Val Lys Ile Thr Ser Pro
180 185 190
Met Lys Thr Phe Ala Asp Ser Thr Ala Ser Lys Glu Asn Ala Pro Val
195 200 205
Ser Met Thr Pro Ala Glu Thr Thr Val Thr Asp Ser His Thr Pro Gly
210 215 220
Arg Thr Asn Pro Ser Phe Gly Thr Leu Tyr Ser Ser Phe Leu Asp Leu
225 230 235 240
Ser Pro Lys Gly Thr Pro Asn Ser Arg Gly Glu Thr Ser Leu Glu Leu
245 250 255
Ile Leu Ser Thr Thr Gly Tyr Pro Phe Ser Ser Pro Glu Pro Gly Ser
260 265 270
Ala Gly His Ser Arg Ile Ser Thr Ser Ala Pro Leu Ser Ser Ser Ala
275 280 285
Ser Val Leu Asp Asn Lys Ile Ser Glu Thr Ser Ile Phe Ser Gly Gln
290 295 300
Ser Leu Thr Ser Pro Leu Ser Pro Gly Val Pro Glu Ala Arg Ala Ser
305 310 315 320
Thr Met Pro Asn Ser Ala Ile Pro Phe Ser Met Thr Leu Ser Asn Ala
325 330 335
Glu Thr Ser Ala Glu Arg Val Arg Ser Thr Ile Ser Ser Leu Gly Thr
340 345 350
Pro Ser Ile Ser Thr Lys Gln Thr Ala Glu Thr Ile Leu Thr Phe His
355 360 365
Ala Phe Ala Glu Thr Met Asp Ile Pro Ser Thr His Ile Ala Lys Thr
370 375 380
Leu Ala Ser Glu Trp Leu Gly Ser Pro Gly Thr Leu Gly Gly Thr Ser
385 390 395 400
Thr Ser Ala Leu Thr Thr Thr Ser Pro Ser Thr Thr Leu Val Ser Glu
405 410 415
Glu Thr Asn Thr His His Ser Thr Ser Gly Lys Glu Thr Glu Gly Thr
420 425 430
Leu Asn Thr Ser Met Thr Pro Leu Glu Thr Ser Ala Pro Gly Glu Glu
435 440 445
Ser Glu Met Thr Ala Thr Leu Val Pro Thr Leu Gly Phe Thr Thr Leu
450 455 460
Asp Ser Lys Ile Arg Ser Pro Ser Gln Val Ser Ser Ser His Pro Thr
465 470 475 480
Arg Glu Leu Arg Thr Thr Gly Ser Thr Ser Gly Arg Gln Ser Ser Ser
485 490 495
Thr Ala Ala His Gly Ser Ser Asp Ile Leu Arg Ala Thr Thr Ser Ser
500 505 510
Thr Ser Lys Ala Ser Ser Trp Thr Ser Glu Ser Thr Ala Gln Gln Phe
515 520 525
Ser Glu Pro Gln His Thr Gln Trp Val Glu Thr Ser Pro Ser Met Lys
530 535 540
Thr Glu Arg Pro Pro Ala Ser Thr Ser Val Ala Ala Pro Ile Thr Thr
545 550 555 560
Ser Val Pro Ser Val Val Ser Gly Phe Thr Thr Leu Lys Thr Ser Ser
565 570 575
Thr Lys Gly Ile Trp Leu Glu Glu Thr Ser Ala Asp Thr Leu Ile Gly
580 585 590
Glu Ser Thr Ala Gly Pro Thr Thr His Gln Phe Ala Val Pro Thr Gly
595 600 605
Ile Ser Met Thr Gly Gly Ser Ser Thr Arg Gly Ser Gln Gly Thr Thr
610 615 620
His Leu Leu Thr Arg Ala Thr Ala Ser Ser Glu Thr Ser Ala Asp Leu
625 630 635 640
Thr Leu Ala Thr Asn Gly Val Pro Val Ser Val Ser Pro Ala Val Ser
645 650 655
Lys Thr Ala Ala Gly Ser Ser Pro Pro Gly Gly Thr Lys Pro Ser Tyr
660 665 670
Thr Met Val Ser Ser Val Ile Pro Glu Thr Ser Ser Leu Gln Ser Ser
675 680 685
Ala Phe Arg Glu Gly Thr Ser Leu Gly Leu Thr Pro Leu Asn Thr Arg
690 695 700
His Pro Phe Ser Ser Pro Glu Pro Asp Ser Ala Gly His Thr Lys Ile
705 710 715 720
Ser Thr Ser Ile Pro Leu Leu Ser Ser Ala Ser Val Leu Glu Asp Lys
725 730 735
Val Ser Ala Thr Ser Thr Phe Ser His His Lys Ala Thr Ser Ser Ile
740 745 750
Thr Thr Gly Thr Pro Glu Ile Ser Thr Lys Thr Lys Pro Ser Ser Ala
755 760 765
Val Leu Ser Ser Met Thr Leu Ser Asn Ala Ala Thr Ser Pro Glu Arg
770 775 780
Val Arg Asn Ala Thr Ser Pro Leu Thr His Pro Ser Pro Ser Gly Glu
785 790 795 800
Glu Thr Ala Gly Ser Val Leu Thr Leu Ser Thr Ser Ala Glu Thr Thr
805 810 815
Asp Ser Pro Asn Ile His Pro Thr Gly Thr Leu Thr Ser Glu Ser Ser
820 825 830
Glu Ser Pro Ser Thr Leu Ser Leu Pro Ser Val Ser Gly Val Lys Thr
835 840 845
Thr Phe Ser Ser Ser Thr Pro Ser Thr His Leu Phe Thr Ser Gly Glu
850 855 860
Glu Thr Glu Glu Thr Ser Asn Pro Ser Val Ser Gln Pro Glu Thr Ser
865 870 875 880
Val Ser Arg Val Arg Thr Thr Leu Ala Ser Thr Ser Val Pro Thr Pro
885 890 895
Val Phe Pro Thr Met Asp Thr Trp Pro Thr Arg Ser Ala Gln Phe Ser
900 905 910
Ser Ser His Leu Val Ser Glu Leu Arg Ala Thr Ser Ser Thr Ser Val
915 920 925
Thr Asn Ser Thr Gly Ser Ala Leu Pro Lys Ile Ser His Leu Thr Gly
930 935 940
Thr Ala Thr Met Ser Gln Thr Asn Arg Asp Thr Phe Asn Asp Ser Ala
945 950 955 960
Ala Pro Gln Ser Thr Thr Trp Pro Glu Thr Ser Pro Arg Phe Lys Thr
965 970 975
Gly Leu Pro Ser Ala Thr Thr Thr Val Ser Thr Ser Ala Thr Ser Leu
980 985 990
Ser Ala Thr Val Met Val Ser Lys Phe Thr Ser Pro Ala Thr Ser Ser
995 1000 1005
Met Glu Ala Thr Ser Ile Arg Glu Pro Ser Thr Thr Ile Leu Thr Thr
1010 1015 1020
Glu Thr Thr Asn Gly Pro Gly Ser Met Ala Val Ala Ser Thr Asn Ile
1025 1030 1035 1040
Pro Ile Gly Lys Gly Tyr Ile Thr Glu Gly Arg Leu Asp Thr Ser His
1045 1050 1055
Leu Pro Ile Gly Thr Thr Ala Ser Ser Glu Thr Ser Met Asp Phe Thr
1060 1065 1070
Met Ala Lys Glu Ser Val Ser Met Ser Val Ser Pro Ser Gln Ser Met
1075 1080 1085
Asp Ala Ala Gly Ser Ser Thr Pro Gly Arg Thr Ser Gln Phe Val Asp
1090 1095 1100
Thr Phe Ser Asp Asp Val Tyr His Leu Thr Ser Arg Glu Ile Thr Ile
1105 1110 1115 1120
Pro Arg Asp Gly Thr Ser Ser Ala Leu Thr Pro Gln Met Thr Ala Thr
1125 1130 1135
His Pro Pro Ser Pro Asp Pro Gly Ser Ala Arg Ser Thr Trp Leu Gly
1140 1145 1150
Ile Leu Ser Ser Ser Pro Ser Ser Pro Thr Pro Lys Val Thr Met Ser
1155 1160 1165
Ser Thr Phe Ser Thr Gln Arg Val Thr Thr Ser Met Ile Met Asp Thr
1170 1175 1180
Val Glu Thr Ser Arg Trp Asn Met Pro Asn Leu Pro Ser Thr Thr Ser
1185 1190 1195 1200
Leu Thr Pro Ser Asn Ile Pro Thr Ser Gly Ala Ile Gly Lys Ser Thr
1205 1210 1215
Leu Val Pro Leu Asp Thr Pro Ser Pro Ala Thr Ser Leu Glu Ala Ser
1220 1225 1230
Glu Gly Gly Leu Pro Thr Leu Ser Thr Tyr Pro Glu Ser Thr Asn Thr
1235 1240 1245
Pro Ser Ile His Leu Gly Ala His Ala Ser Ser Glu Ser Pro Ser Thr
1250 1255 1260
Ile Lys Leu Thr Met Ala Ser Val Val Lys Pro Gly Ser Tyr Thr Pro
1265 1270 1275 1280
Leu Thr Phe Pro Ser Ile Glu Thr His Ile His Val Ser Thr Ala Arg
1285 1290 1295
Met Ala Tyr Ser Ser Gly Ser Ser Pro Glu Met Thr Ala Pro Gly Glu
1300 1305 1310
Thr Asn Thr Gly Ser Thr Trp Asp Pro Thr Thr Tyr Ile Thr Thr Thr
1315 1320 1325
Asp Pro Lys Asp Thr Ser Ser Ala Gln Val Ser Thr Pro His Ser Val
1330 1335 1340
Arg Thr Leu Arg Thr Thr Glu Asn His Pro Lys Thr Glu Ser Ala Thr
1345 1350 1355 1360
Pro Ala Ala Tyr Ser Gly Ser Pro Lys Ile Ser Ser Ser Pro Asn Leu
1365 1370 1375
Thr Ser Pro Ala Thr Lys Ala Trp Thr Ile Thr Asp Thr Thr Glu His
1380 1385 1390
Ser Thr Gln Leu His Tyr Thr Lys Leu Ala Glu Lys Ser Ser Gly Phe
1395 1400 1405
Glu Thr Gln Ser Ala Pro Gly Pro Val Ser Val Val Ile Pro Thr Ser
1410 1415 1420
Pro Thr Ile Gly Ser Ser Thr Leu Glu Leu Thr Ser Asp Val Pro Gly
1425 1430 1435 1440
Glu Pro Leu Val Leu Ala Pro Ser Glu Gln Thr Thr Ile Thr Leu Pro
1445 1450 1455
Met Ala Thr Trp Leu Ser Thr Ser Leu Thr Glu Glu Met Ala Ser Thr
1460 1465 1470
Asp Leu Asp Ile Ser Ser Pro Ser Ser Pro Met Ser Thr Phe Ala Ile
1475 1480 1485
Phe Pro Pro Met Ser Thr Pro Ser His Glu Leu Ser Lys Ser Glu Ala
1490 1495 1500
Asp Thr Ser Ala Ile Arg Asn Thr Asp Ser Thr Thr Leu Asp Gln His
1505 1510 1515 1520
Leu Gly Ile Arg Ser Leu Gly Arg Thr Gly Asp Leu Thr Thr Val Pro
1525 1530 1535
Ile Thr Pro Leu Thr Thr Thr Trp Thr Ser Val Ile Glu His Ser Thr
1540 1545 1550
Gln Ala Gln Asp Thr Leu Ser Ala Thr Met Ser Pro Thr His Val Thr
1555 1560 1565
Gln Ser Leu Lys Asp Gln Thr Ser Ile Pro Ala Ser Ala Ser Pro Ser
1570 1575 1580
His Leu Thr Glu Val Tyr Pro Glu Leu Gly Thr Gln Gly Arg Ser Ser
1585 1590 1595 1600
Ser Glu Ala Thr Thr Phe Trp Lys Pro Ser Thr Asp Thr Leu Ser Arg
1605 1610 1615
Glu Ile Glu Thr Gly Pro Thr Asn Ile Gln Ser Thr Pro Pro Met Asp
1620 1625 1630
Asn Thr Thr Thr Gly Ser Ser Ser Ser Gly Val Thr Leu Gly Ile Ala
1635 1640 1645
His Leu Pro Ile Gly Thr Ser Ser Pro Ala Glu Thr Ser Thr Asn Met
1650 1655 1660
Ala Leu Glu Arg Arg Ser Ser Thr Ala Thr Val Ser Met Ala Gly Thr
1665 1670 1675 1680
Met Gly Leu Leu Val Thr Ser Ala Pro Gly Arg Ser Ile Ser Gln Ser
1685 1690 1695
Leu Gly Arg Val Ser Ser Val Leu Ser Glu Ser Thr Thr Glu Gly Val
1700 1705 1710
Thr Asp Ser Ser Lys Gly Ser Ser Pro Arg Leu Asn Thr Gln Gly Asn
1715 1720 1725
Thr Ala Leu Ser Ser Ser Leu Glu Pro Ser Tyr Ala Glu Gly Ser Gln
1730 1735 1740
Met Ser Thr Ser Ile Pro Leu Thr Ser Ser Pro Thr Thr Pro Asp Val
1745 1750 1755 1760
Glu Phe Ile Gly Gly Ser Thr Phe Trp Thr Lys Glu Val Thr Thr Val
1765 1770 1775
Met Thr Ser Asp Ile Ser Lys Ser Ser Ala Arg Thr Glu Ser Ser Ser
1780 1785 1790
Ala Thr Leu Met Ser Thr Ala Leu Gly Ser Thr Glu Asn Thr Gly Lys
1795 1800 1805
Glu Lys Leu Arg Thr Ala Ser Met Asp Leu Pro Ser Pro Thr Pro Ser
1810 1815 1820
Met Glu Val Thr Pro Trp Ile Ser Leu Thr Leu Ser Asn Ala Pro Asn
1825 1830 1835 1840
Thr Thr Asp Ser Leu Asp Leu Ser His Gly Val His Thr Ser Ser Ala
1845 1850 1855
Gly Thr Leu Ala Thr Asp Arg Ser Leu Asn Thr Gly Val Thr Arg Ala
1860 1865 1870
Ser Arg Leu Glu Asn Gly Ser Asp Thr Ser Ser Lys Ser Leu Ser Met
1875 1880 1885
Gly Asn Ser Thr His Thr Ser Met Thr Tyr Thr Glu Lys Ser Glu Val
1890 1895 1900
Ser Ser Ser Ile His Pro Arg Pro Glu Thr Ser Ala Pro Gly Ala Glu
1905 1910 1915 1920
Thr Thr Leu Thr Ser Thr Pro Gly Asn Arg Ala Ile Ser Leu Thr Leu
1925 1930 1935
Pro Phe Ser Ser Ile Pro Val Glu Glu Val Ile Ser Thr Gly Ile Thr
1940 1945 1950
Ser Gly Pro Asp Ile Asn Ser Ala Pro Met Thr His Ser Pro Ile Thr
1955 1960 1965
Pro Pro Thr Ile Val Trp Thr Ser Thr Gly Thr Ile Glu Gln Ser Thr
1970 1975 1980
Gln Pro Leu His Ala Val Ser Ser Glu Lys Val Ser Val Gln Thr Gln
1985 1990 1995 2000
Ser Thr Pro Tyr Val Asn Ser Val Ala Val Ser Ala Ser Pro Thr His
2005 2010 2015
Glu Asn Ser Val Ser Ser Gly Ser Ser Thr Ser Ser Pro Tyr Ser Ser
2020 2025 2030
Ala Ser Leu Glu Ser Leu Asp Ser Thr Ile Ser Arg Arg Asn Ala Ile
2035 2040 2045
Thr Ser Trp Leu Trp Asp Leu Thr Thr Ser Leu Pro Thr Thr Thr Trp
2050 2055 2060
Pro Ser Thr Ser Leu Ser Glu Ala Leu Ser Ser Gly His Ser Gly Val
2065 2070 2075 2080
Ser Asn Pro Ser Ser Thr Thr Thr Glu Phe Pro Leu Phe Ser Ala Ala
2085 2090 2095
Ser Thr Ser Ala Ala Lys Gln Arg Asn Pro Glu Thr Glu Thr His Gly
2100 2105 2110
Pro Gln Asn Thr Ala Ala Ser Thr Leu Asn Thr Asp Ala Ser Ser Val
2115 2120 2125
Thr Gly Leu Ser Glu Thr Pro Val Gly Ala Ser Ile Ser Ser Glu Val
2130 2135 2140
Pro Leu Pro Met Ala Ile Thr Ser Arg Ser Asp Val Ser Gly Leu Thr
2145 2150 2155 2160
Ser Glu Ser Thr Ala Asn Pro Ser Leu Gly Thr Ala Ser Ser Ala Gly
2165 2170 2175
Thr Lys Leu Thr Arg Thr Ile Ser Leu Pro Thr Ser Glu Ser Leu Val
2180 2185 2190
Ser Phe Arg Met Asn Lys Asp Pro Trp Thr Val Ser Ile Pro Leu Gly
2195 2200 2205
Ser His Pro Thr Thr Asn Thr Glu Thr Ser Ile Pro Val Asn Ser Ala
2210 2215 2220
Gly Pro Pro Gly Leu Ser Thr Val Ala Ser Asp Val Ile Asp Thr Pro
2225 2230 2235 2240
Ser Asp Gly Ala Glu Ser Ile Pro Thr Val Ser Phe Ser Pro Ser Pro
2245 2250 2255
Asp Thr Glu Val Thr Thr Ile Ser His Phe Pro Glu Lys Thr Thr His
2260 2265 2270
Ser Phe Arg Thr Ile Ser Ser Leu Thr His Glu Leu Thr Ser Arg Val
2275 2280 2285
Thr Pro Ile Pro Gly Asp Trp Met Ser Ser Ala Met Ser Thr Lys Pro
2290 2295 2300
Thr Gly Ala Ser Pro Ser Ile Thr Leu Gly Glu Arg Arg Thr Ile Thr
2305 2310 2315 2320
Ser Ala Ala Pro Thr Thr Ser Pro Ile Val Leu Thr Ala Ser Phe Thr
2325 2330 2335
Glu Thr Ser Thr Val Ser Leu Asp Asn Glu Thr Thr Val Lys Thr Ser
2340 2345 2350
Asp Ile Leu Asp Ala Arg Lys Thr Asn Glu Leu Pro Ser Asp Ser Ser
2355 2360 2365
Ser Ser Ser Asp Leu Ile Asn Thr Ser Ile Ala Ser Ser Thr Met Asp
2370 2375 2380
Val Thr Lys Thr Ala Ser Ile Ser Pro Thr Ser Ile Ser Gly Met Thr
2385 2390 2395 2400
Ala Ser Ser Ser Pro Ser Leu Phe Ser Ser Asp Arg Pro Gln Val Pro
2405 2410 2415
Thr Ser Thr Thr Glu Thr Asn Thr Ala Thr Ser Pro Ser Val Ser Ser
2420 2425 2430
Asn Thr Tyr Ser Leu Asp Gly Gly Ser Asn Val Gly Gly Thr Pro Ser
2435 2440 2445
Thr Leu Pro Pro Phe Thr Ile Thr His Pro Val Glu Thr Ser Ser Ala
2450 2455 2460
Leu Leu Ala Trp Ser Arg Pro Val Arg Thr Phe Ser Thr Met Val Ser
2465 2470 2475 2480
Thr Asp Thr Ala Ser Gly Glu Asn Pro Thr Ser Ser Asn Ser Val Val
2485 2490 2495
Thr Ser Val Pro Ala Pro Gly Thr Trp Thr Ser Val Gly Ser Thr Thr
2500 2505 2510
Asp Leu Pro Ala Met Gly Phe Leu Lys Thr Ser Pro Ala Gly Glu Ala
2515 2520 2525
His Ser Leu Leu Ala Ser Thr Ile Glu Pro Ala Thr Ala Phe Thr Pro
2530 2535 2540
His Leu Ser Ala Ala Val Val Thr Gly Ser Ser Ala Thr Ser Glu Ala
2545 2550 2555 2560
Ser Leu Leu Thr Thr Ser Glu Ser Lys Ala Ile His Ser Ser Pro Gln
2565 2570 2575
Thr Pro Thr Thr Pro Thr Ser Gly Ala Asn Trp Glu Thr Ser Ala Thr
2580 2585 2590
Pro Glu Ser Leu Leu Val Val Thr Glu Thr Ser Asp Thr Thr Leu Thr
2595 2600 2605
Ser Lys Ile Leu Val Thr Asp Thr Ile Leu Phe Ser Thr Val Ser Thr
2610 2615 2620
Pro Pro Ser Lys Phe Pro Ser Thr Gly Thr Leu Ser Gly Ala Ser Phe
2625 2630 2635 2640
Pro Thr Leu Leu Pro Asp Thr Pro Ala Ile Pro Leu Thr Ala Thr Glu
2645 2650 2655
Pro Thr Ser Ser Leu Ala Thr Ser Phe Asp Ser Thr Pro Leu Val Thr
2660 2665 2670
Ile Ala Ser Asp Ser Leu Gly Thr Val Pro Glu Thr Thr Leu Thr Met
2675 2680 2685
Ser Glu Thr Ser Asn Gly Asp Ala Leu Val Leu Lys Thr Val Ser Asn
2690 2695 2700
Pro Asp Arg Ser Ile Pro Gly Ile Thr Ile Gln Gly Val Thr Glu Ser
2705 2710 2715 2720
Pro Leu His Pro Ser Ser Thr Ser Pro Ser Lys Ile Val Ala Pro Arg
2725 2730 2735
Asn Thr Thr Tyr Glu Gly Ser Ile Thr Val Ala Leu Ser Thr Leu Pro
2740 2745 2750
Ala Gly Thr Thr Gly Ser Leu Val Phe Ser Gln Ser Ser Glu Asn Ser
2755 2760 2765
Glu Thr Thr Ala Leu Val Asp Ser Ser Ala Gly Leu Glu Arg Ala Ser
2770 2775 2780
Val Met Pro Leu Thr Thr Gly Ser Gln Gly Met Ala Ser Ser Gly Gly
2785 2790 2795 2800
Ile Arg Ser Gly Ser Thr His Ser Thr Gly Thr Lys Thr Phe Ser Ser
2805 2810 2815
Leu Pro Leu Thr Met Asn Pro Gly Glu Val Thr Ala Met Ser Glu Ile
2820 2825 2830
Thr Thr Asn Arg Leu Thr Ala Thr Gln Ser Thr Ala Pro Lys Gly Ile
2835 2840 2845
Pro Val Lys Pro Thr Ser Ala Glu Ser Gly Leu Leu Thr Pro Val Ser
2850 2855 2860
Ala Ser Ser Ser Pro Ser Lys Ala Phe Ala Ser Leu Thr Thr Ala Pro
2865 2870 2875 2880
Pro Thr Trp Gly Ile Pro Gln Ser Thr Leu Thr Phe Glu Phe Ser Glu
2885 2890 2895
Val Pro Ser Leu Asp Thr Lys Ser Ala Ser Leu Pro Thr Pro Gly Gln
2900 2905 2910
Ser Leu Asn Thr Ile Pro Asp Ser Asp Ala Ser Thr Ala Ser Ser Ser
2915 2920 2925
Leu Ser Lys Ser Pro Glu Lys Asn Pro Arg Ala Arg Met Met Thr Ser
2930 2935 2940
Thr Lys Ala Ile Ser Ala Ser Ser Phe Gln Ser Thr Gly Phe Thr Glu
2945 2950 2955 2960
Thr Pro Glu Gly Ser Ala Ser Pro Ser Met Ala Gly His Glu Pro Arg
2965 2970 2975
Val Pro Thr Ser Gly Thr Gly Asp Pro Arg Tyr Ala Ser Glu Ser Met
2980 2985 2990
Ser Tyr Pro Asp Pro Ser Lys Ala Ser Ser Ala Met Thr Ser Thr Ser
2995 3000 3005
Leu Ala Ser Lys Leu Thr Thr Leu Phe Ser Thr Gly Gln Ala Ala Arg
3010 3015 3020
Ser Gly Ser Ser Ser Ser Pro Ile Ser Leu Ser Thr Glu Lys Glu Thr
3025 3030 3035 3040
Ser Phe Leu Ser Pro Thr Ala Ser Thr Ser Arg Lys Thr Ser Leu Phe
3045 3050 3055
Leu Gly Pro Ser Met Ala Arg Gln Pro Asn Ile Leu Val His Leu Gln
3060 3065 3070
Thr Ser Ala Leu Thr Leu Ser Pro Thr Ser Thr Leu Asn Met Ser Gln
3075 3080 3085
Glu Glu Pro Pro Glu Leu Thr Ser Ser Gln Thr Ile Ala Glu Glu Glu
3090 3095 3100
Gly Thr Thr Ala Glu Thr Gln Thr Leu Thr Phe Thr Pro Ser Glu Thr
3105 3110 3115 3120
Pro Thr Ser Leu Leu Pro Val Ser Ser Pro Thr Glu Pro Thr Ala Arg
3125 3130 3135
Arg Lys Ser Ser Pro Glu Thr Trp Ala Ser Ser Ile Ser Val Pro Ala
3140 3145 3150
Lys Thr Ser Leu Val Glu Thr Thr Asp Gly Thr Leu Val Thr Thr Ile
3155 3160 3165
Lys Met Ser Ser Gln Ala Ala Gln Gly Asn Ser Thr Trp Pro Ala Pro
3170 3175 3180
Ala Glu Glu Thr Gly Ser Ser Pro Ala Gly Thr Ser Pro Gly Ser Pro
3185 3190 3195 3200
Glu Met Ser Thr Thr Leu Lys Ile Met Ser Ser Lys Glu Pro Ser Ile
3205 3210 3215
Ser Pro Glu Ile Arg Ser Thr Val Arg Asn Ser Pro Trp Lys Thr Pro
3220 3225 3230
Glu Thr Thr Val Pro Met Glu Thr Thr Val Glu Pro Val Thr Leu Gln
3235 3240 3245
Ser Thr Ala Leu Gly Ser Gly Ser Thr Ser Ile Ser His Leu Pro Thr
3250 3255 3260
Gly Thr Thr Ser Pro Thr Lys Ser Pro Thr Glu Asn Met Leu Ala Thr
3265 3270 3275 3280
Glu Arg Val Ser Leu Ser Pro Ser Pro Pro Glu Ala Trp Thr Asn Leu
3285 3290 3295
Tyr Ser Gly Thr Pro Gly Gly Thr Arg Gln Ser Leu Ala Thr Met Ser
3300 3305 3310
Ser Val Ser Leu Glu Ser Pro Thr Ala Arg Ser Ile Thr Gly Thr Gly
3315 3320 3325
Gln Gln Ser Ser Pro Glu Leu Val Ser Lys Thr Thr Gly Met Glu Phe
3330 3335 3340
Ser Met Trp His Gly Ser Thr Gly Gly Thr Thr Gly Asp Thr His Val
3345 3350 3355 3360
Ser Leu Ser Thr Ser Ser Asn Ile Leu Glu Asp Pro Val Thr Ser Pro
3365 3370 3375
Asn Ser Val Ser Ser Leu Thr Asp Lys Ser Lys His Lys Thr Glu Thr
3380 3385 3390
Trp Val Ser Thr Thr Ala Ile Pro Ser Thr Val Leu Asn Asn Lys Ile
3395 3400 3405
Met Ala Ala Glu Gln Gln Thr Ser Arg Ser Val Asp Glu Ala Tyr Ser
3410 3415 3420
Ser Thr Ser Ser Trp Ser Asp Gln Thr Ser Gly Ser Asp Ile Thr Leu
3425 3430 3435 3440
Gly Ala Ser Pro Asp Val Thr Asn Thr Leu Tyr Ile Thr Ser Thr Ala
3445 3450 3455
Gln Thr Thr Ser Leu Val Ser Leu Pro Ser Gly Asp Gln Gly Ile Thr
3460 3465 3470
Ser Leu Thr Asn Pro Ser Gly Gly Lys Thr Ser Ser Ala Ser Ser Val
3475 3480 3485
Thr Ser Pro Ser Ile Gly Leu Glu Thr Leu Arg Ala Asn Val Ser Ala
3490 3495 3500
Val Lys Ser Asp Ile Ala Pro Thr Ala Gly His Leu Ser Gln Thr Ser
3505 3510 3515 3520
Ser Pro Ala Glu Val Ser Ile Leu Asp Val Thr Thr Ala Pro Thr Pro
3525 3530 3535
Gly Ile Ser Thr Thr Ile Thr Thr Met Gly Thr Asn Ser Ile Ser Thr
3540 3545 3550
Thr Thr Pro Asn Pro Glu Val Gly Met Ser Thr Met Asp Ser Thr Pro
3555 3560 3565
Ala Thr Glu Arg Arg Thr Thr Ser Thr Glu His Pro Ser Thr Trp Ser
3570 3575 3580
Ser Thr Ala Ala Ser Asp Ser Trp Thr Val Thr Asp Met Thr Ser Asn
3585 3590 3595 3600
Leu Lys Val Ala Arg Ser Pro Gly Thr Ile Ser Thr Met His Thr Thr
3605 3610 3615
Ser Phe Leu Ala Ser Ser Thr Glu Leu Asp Ser Met Ser Thr Pro His
3620 3625 3630
Gly Arg Ile Thr Val Ile Gly Thr Ser Leu Val Thr Pro Ser Ser Asp
3635 3640 3645
Ala Ser Ala Val Lys Thr Glu Thr Ser Thr Ser Glu Arg Thr Leu Ser
3650 3655 3660
Pro Ser Asp Thr Thr Ala Ser Thr Pro Ile Ser Thr Phe Ser Arg Val
3665 3670 3675 3680
Gln Arg Met Ser Ile Ser Val Pro Asp Ile Leu Ser Thr Ser Trp Thr
3685 3690 3695
Pro Ser Ser Thr Glu Ala Glu Asp Val Pro Val Ser Met Val Ser Thr
3700 3705 3710
Asp His Ala Ser Thr Lys Thr Asp Pro Asn Thr Pro Leu Ser Thr Phe
3715 3720 3725
Leu Phe Asp Ser Leu Ser Thr Leu Asp Trp Asp Thr Gly Arg Ser Leu
3730 3735 3740
Ser Ser Ala Thr Ala Thr Thr Ser Ala Pro Gln Gly Ala Thr Thr Pro
3745 3750 3755 3760
Gln Glu Leu Thr Leu Glu Thr Met Ile Ser Pro Ala Thr Ser Gln Leu
3765 3770 3775
Pro Phe Ser Ile Gly His Ile Thr Ser Ala Val Thr Pro Ala Ala Met
3780 3785 3790
Ala Arg Ser Ser Gly Val Thr Phe Ser Arg Pro Asp Pro Thr Ser Lys
3795 3800 3805
Lys Ala Glu Gln Thr Ser Thr Gln Leu Pro Thr Thr Thr Ser Ala His
3810 3815 3820
Pro Gly Gln Val Pro Arg Ser Ala Ala Thr Thr Leu Asp Val Ile Pro
3825 3830 3835 3840
His Thr Ala Lys Thr Pro Asp Ala Thr Phe Gln Arg Gln Gly Gln Thr
3845 3850 3855
Ala Leu Thr Thr Glu Ala Arg Ala Thr Ser Asp Ser Trp Asn Glu Lys
3860 3865 3870
Glu Lys Ser Thr Pro Ser Ala Pro Trp Ile Thr Glu Met Met Asn Ser
3875 3880 3885
Val Ser Glu Asp Thr Ile Lys Glu Val Thr Ser Ser Ser Ser Val Leu
3890 3895 3900
Arg Thr Leu Asn Thr Leu Asp Ile Asn Leu Glu Ser Gly Thr Thr Ser
3905 3910 3915 3920
Ser Pro Ser Trp Lys Ser Ser Pro Tyr Glu Arg Ile Ala Pro Ser Glu
3925 3930 3935
Ser Thr Thr Asp Lys Glu Ala Ile His Pro Ser Thr Asn Thr Val Glu
3940 3945 3950
Thr Thr Gly Trp Val Thr Ser Ser Glu His Ala Ser His Ser Thr Ile
3955 3960 3965
Pro Ala His Ser Ala Ser Ser Lys Leu Thr Ser Pro Val Val Thr Thr
3970 3975 3980
Ser Thr Arg Glu Gln Ala Ile Val Ser Met Ser Thr Thr Thr Trp Pro
3985 3990 3995 4000
Glu Ser Thr Arg Ala Arg Thr Glu Pro Asn Ser Phe Leu Thr Ile Glu
4005 4010 4015
Leu Arg Asp Val Ser Pro Tyr Met Asp Thr Ser Ser Thr Thr Gln Thr
4020 4025 4030
Ser Ile Ile Ser Ser Pro Gly Ser Thr Ala Ile Thr Lys Gly Pro Arg
4035 4040 4045
Thr Glu Ile Thr Ser Ser Lys Arg Ile Ser Ser Ser Phe Leu Ala Gln
4050 4055 4060
Ser Met Arg Ser Ser Asp Ser Pro Ser Glu Ala Ile Thr Arg Leu Ser
4065 4070 4075 4080
Asn Phe Pro Ala Met Thr Glu Ser Gly Gly Met Ile Leu Ala Met Gln
4085 4090 4095
Thr Ser Pro Pro Gly Ala Thr Ser Leu Ser Ala Pro Thr Leu Asp Thr
4100 4105 4110
Ser Ala Thr Ala Ser Trp Thr Gly Thr Pro Leu Ala Thr Thr Gln Arg
4115 4120 4125
Phe Thr Tyr Ser Glu Lys Thr Thr Leu Phe Ser Lys Gly Pro Glu Asp
4130 4135 4140
Thr Ser Gln Pro Ser Pro Pro Ser Val Glu Glu Thr Ser Ser Ser Ser
4145 4150 4155 4160
Ser Leu Val Pro Ile His Ala Thr Thr Ser Pro Ser Asn Ile Leu Leu
4165 4170 4175
Thr Ser Gln Gly His Ser Pro Ser Ser Thr Pro Pro Val Thr Ser Val
4180 4185 4190
Phe Leu Ser Glu Thr Ser Gly Leu Gly Lys Thr Thr Asp Met Ser Arg
4195 4200 4205
Ile Ser Leu Glu Pro Gly Thr Ser Leu Pro Pro Asn Leu Ser Ser Thr
4210 4215 4220
Ala Gly Glu Ala Leu Ser Thr Tyr Glu Ala Ser Arg Asp Thr Lys Ala
4225 4230 4235 4240
Ile His His Ser Ala Asp Thr Ala Val Thr Asn Met Glu Ala Thr Ser
4245 4250 4255
Ser Glu Tyr Ser Pro Ile Pro Gly His Thr Lys Pro Ser Lys Ala Thr
4260 4265 4270
Ser Pro Leu Val Thr Ser His Ile Met Gly Asp Ile Thr Ser Ser Thr
4275 4280 4285
Ser Val Phe Gly Ser Ser Glu Thr Thr Glu Ile Glu Thr Val Ser Ser
4290 4295 4300
Val Asn Gln Gly Leu Gln Glu Arg Ser Thr Ser Gln Val Ala Ser Ser
4305 4310 4315 4320
Ala Thr Glu Thr Ser Thr Val Ile Thr His Val Ser Ser Gly Asp Ala
4325 4330 4335
Thr Thr His Val Thr Lys Thr Gln Ala Thr Phe Ser Ser Gly Thr Ser
4340 4345 4350
Ile Ser Ser Pro His Gln Phe Ile Thr Ser Thr Asn Thr Phe Thr Asp
4355 4360 4365
Val Ser Thr Asn Pro Ser Thr Ser Leu Ile Met Thr Glu Ser Ser Gly
4370 4375 4380
Val Thr Ile Thr Thr Gln Thr Gly Pro Thr Gly Ala Ala Thr Gln Gly
4385 4390 4395 4400
Pro Tyr Leu Leu Asp Thr Ser Thr Met Pro Tyr Leu Thr Glu Thr Pro
4405 4410 4415
Leu Ala Val Thr Pro Asp Phe Met Gln Ser Glu Lys Thr Thr Leu Ile
4420 4425 4430
Ser Lys Gly Pro Lys Asp Val Ser Trp Thr Ser Pro Pro Ser Val Ala
4435 4440 4445
Glu Thr Ser Tyr Pro Ser Ser Leu Thr Pro Phe Leu Val Thr Thr Ile
4450 4455 4460
Pro Pro Ala Thr Ser Thr Leu Gln Gly Gln His Thr Ser Ser Pro Val
4465 4470 4475 4480
Ser Ala Thr Ser Val Leu Thr Ser Gly Leu Val Lys Thr Thr Asp Met
4485 4490 4495
Leu Asn Thr Ser Met Glu Pro Val Thr Asn Ser Pro Gln Asn Leu Asn
4500 4505 4510
Asn Pro Ser Asn Glu Ile Leu Ala Thr Leu Ala Ala Thr Thr Asp Ile
4515 4520 4525
Glu Thr Ile His Pro Ser Ile Asn Lys Ala Val Thr Asn Met Gly Thr
4530 4535 4540
Ala Ser Ser Ala His Val Leu His Ser Thr Leu Pro Val Ser Ser Glu
4545 4550 4555 4560
Pro Ser Thr Ala Thr Ser Pro Met Val Pro Ala Ser Ser Met Gly Asp
4565 4570 4575
Ala Leu Ala Ser Ile Ser Ile Pro Gly Ser Glu Thr Thr Asp Ile Glu
4580 4585 4590
Gly Glu Pro Thr Ser Ser Leu Thr Ala Gly Arg Lys Glu Asn Ser Thr
4595 4600 4605
Leu Gln Glu Met Asn Ser Thr Thr Glu Ser Asn Ile Ile Leu Ser Asn
4610 4615 4620
Val Ser Val Gly Ala Ile Thr Glu Ala Thr Lys Met Glu Val Pro Ser
4625 4630 4635 4640
Phe Asp Ala Thr Phe Ile Pro Thr Pro Ala Gln Ser Thr Lys Phe Pro
4645 4650 4655
Asp Ile Phe Ser Val Ala Ser Ser Arg Leu Ser Asn Ser Pro Pro Met
4660 4665 4670
Thr Ile Ser Thr His Met Thr Thr Thr Gln Thr Gly Ser Ser Gly Ala
4675 4680 4685
Thr Ser Lys Ile Pro Leu Ala Leu Asp Thr Ser Thr Leu Glu Thr Ser
4690 4695 4700
Ala Gly Thr Pro Ser Val Val Thr Glu Gly Phe Ala His Ser Lys Ile
4705 4710 4715 4720
Thr Thr Ala Met Asn Asn Asp Val Lys Asp Val Ser Gln Thr Asn Pro
4725 4730 4735
Pro Phe Gln Asp Glu Ala Ser Ser Pro Ser Ser Gln Ala Pro Val Leu
4740 4745 4750
Val Thr Thr Leu Pro Ser Ser Val Ala Phe Thr Pro Gln Trp His Ser
4755 4760 4765
Thr Ser Ser Pro Val Ser Met Ser Ser Val Leu Thr Ser Ser Leu Val
4770 4775 4780
Lys Thr Ala Gly Lys Val Asp Thr Ser Leu Glu Thr Val Thr Ser Ser
4785 4790 4795 4800
Pro Gln Ser Met Ser Asn Thr Leu Asp Asp Ile Ser Val Thr Ser Ala
4805 4810 4815
Ala Thr Thr Asp Ile Glu Thr Thr His Pro Ser Ile Asn Thr Val Val
4820 4825 4830
Thr Asn Val Gly Thr Thr Gly Ser Ala Phe Glu Ser His Ser Thr Val
4835 4840 4845
Ser Ala Tyr Pro Glu Pro Ser Lys Val Thr Ser Pro Asn Val Thr Thr
4850 4855 4860
Ser Thr Met Glu Asp Thr Thr Ile Ser Arg Ser Ile Pro Lys Ser Ser
4865 4870 4875 4880
Lys Thr Thr Arg Thr Glu Thr Glu Thr Thr Ser Ser Leu Thr Pro Lys
4885 4890 4895
Leu Arg Glu Thr Ser Ile Ser Gln Glu Ile Thr Ser Ser Thr Glu Thr
4900 4905 4910
Ser Thr Val Pro Tyr Lys Glu Leu Thr Gly Ala Thr Thr Glu Val Ser
4915 4920 4925
Arg Thr Asp Val Thr Ser Ser Ser Ser Thr Ser Phe Pro Gly Pro Asp
4930 4935 4940
Gln Ser Thr Val Ser Leu Asp Ile Ser Thr Glu Thr Asn Thr Arg Leu
4945 4950 4955 4960
Ser Thr Ser Pro Ile Met Thr Glu Ser Ala Glu Ile Thr Ile Thr Thr
4965 4970 4975
Gln Thr Gly Pro His Gly Ala Thr Ser Gln Asp Thr Phe Thr Met Asp
4980 4985 4990
Pro Ser Asn Thr Thr Pro Gln Ala Gly Ile His Ser Ala Met Thr His
4995 5000 5005
Gly Phe Ser Gln Leu Asp Val Thr Thr Leu Met Ser Arg Ile Pro Gln
5010 5015 5020
Asp Val Ser Trp Thr Ser Pro Pro Ser Val Asp Lys Thr Ser Ser Pro
5025 5030 5035 5040
Ser Ser Phe Leu Ser Ser Pro Ala Met Thr Thr Pro Ser Leu Ile Ser
5045 5050 5055
Ser Thr Leu Pro Glu Asp Lys Leu Ser Ser Pro Met Thr Ser Leu Leu
5060 5065 5070
Thr Ser Gly Leu Val Lys Ile Thr Asp Ile Leu Arg Thr Arg Leu Glu
5075 5080 5085
Pro Val Thr Ser Ser Leu Pro Asn Phe Ser Ser Thr Ser Asp Lys Ile
5090 5095 5100
Leu Ala Thr Ser Lys Asp Ser Lys Asp Thr Lys Glu Ile Phe Pro Ser
5105 5110 5115 5120
Ile Asn Thr Glu Glu Thr Asn Val Lys Ala Asn Asn Ser Gly His Glu
5125 5130 5135
Ser His Ser Pro Ala Leu Ala Asp Ser Glu Thr Pro Lys Ala Thr Thr
5140 5145 5150
Gln Met Val Ile Thr Thr Thr Val Gly Asp Pro Ala Pro Ser Thr Ser
5155 5160 5165
Met Pro Val His Gly Ser Ser Glu Thr Thr Asn Ile Lys Arg Glu Pro
5170 5175 5180
Thr Tyr Phe Leu Thr Pro Arg Leu Arg Glu Thr Ser Thr Ser Gln Glu
5185 5190 5195 5200
Ser Ser Phe Pro Thr Asp Thr Ser Phe Leu Leu Ser Lys Val Pro Thr
5205 5210 5215
Gly Thr Ile Thr Glu Val Ser Ser Thr Gly Val Asn Ser Ser Ser Lys
5220 5225 5230
Ile Ser Thr Pro Asp His Asp Lys Ser Thr Val Pro Pro Asp Thr Phe
5235 5240 5245
Thr Gly Glu Ile Pro Arg Val Phe Thr Ser Ser Ile Lys Thr Lys Ser
5250 5255 5260
Ala Glu Met Thr Ile Thr Thr Gln Ala Ser Pro Pro Glu Ser Ala Ser
5265 5270 5275 5280
His Ser Thr Leu Pro Leu Asp Thr Ser Thr Thr Leu Ser Gln Gly Gly
5285 5290 5295
Thr His Ser Thr Val Thr Gln Gly Phe Pro Tyr Ser Glu Val Thr Thr
5300 5305 5310
Leu Met Gly Met Gly Pro Gly Asn Val Ser Trp Met Thr Thr Pro Pro
5315 5320 5325
Val Glu Glu Thr Ser Ser Val Ser Ser Leu Met Ser Ser Pro Ala Met
5330 5335 5340
Thr Ser Pro Ser Pro Val Ser Ser Thr Ser Pro Gln Ser Ile Pro Ser
5345 5350 5355 5360
Ser Pro Leu Pro Val Thr Ala Leu Pro Thr Ser Val Leu Val Thr Thr
5365 5370 5375
Thr Asp Val Leu Gly Thr Thr Ser Pro Glu Ser Val Thr Ser Ser Pro
5380 5385 5390
Pro Asn Leu Ser Ser Ile Thr His Glu Arg Pro Ala Thr Tyr Lys Asp
5395 5400 5405
Thr Ala His Thr Glu Ala Ala Met His His Ser Thr Asn Thr Ala Val
5410 5415 5420
Thr Asn Val Gly Thr Ser Gly Ser Gly His Lys Ser Gln Ser Ser Val
5425 5430 5435 5440
Leu Ala Asp Ser Glu Thr Ser Lys Ala Thr Pro Leu Met Ser Thr Thr
5445 5450 5455
Ser Thr Leu Gly Asp Thr Ser Val Ser Thr Ser Thr Pro Asn Ile Ser
5460 5465 5470
Gln Thr Asn Gln Ile Gln Thr Glu Pro Thr Ala Ser Leu Ser Pro Arg
5475 5480 5485
Leu Arg Glu Ser Ser Thr Ser Glu Lys Thr Ser Ser Thr Thr Glu Thr
5490 5495 5500
Asn Thr Ala Phe Ser Tyr Val Pro Thr Gly Ala Ile Thr Gln Ala Ser
5505 5510 5515 5520
Arg Thr Glu Ile Ser Ser Ser Arg Thr Ser Ile Ser Asp Leu Asp Arg
5525 5530 5535
Pro Thr Ile Ala Pro Asp Ile Ser Thr Gly Met Ile Thr Arg Leu Phe
5540 5545 5550
Thr Ser Pro Ile Met Thr Lys Ser Ala Glu Met Thr Val Thr Thr Gln
5555 5560 5565
Thr Thr Thr Pro Gly Ala Thr Ser Gln Gly Ile Leu Pro Trp Asp Thr
5570 5575 5580
Ser Thr Thr Leu Phe Gln Gly Gly Thr His Ser Thr Val Ser Gln Gly
5585 5590 5595 5600
Phe Pro His Ser Glu Ile Thr Thr Leu Arg Ser Arg Thr Pro Gly Asp
5605 5610 5615
Val Ser Trp Met Thr Thr Pro Pro Val Glu Glu Thr Ser Ser Gly Phe
5620 5625 5630
Ser Leu Met Ser Pro Ser Met Thr Ser Pro Ser Pro Val Ser Ser Thr
5635 5640 5645
Ser Pro Glu Ser Ile Pro Ser Ser Pro Leu Pro Val Thr Ala Leu Leu
5650 5655 5660
Thr Ser Val Leu Val Thr Thr Thr Asn Val Leu Gly Thr Thr Ser Pro
5665 5670 5675 5680
Glu Pro Val Thr Ser Ser Pro Pro Asn Leu Ser Ser Pro Thr Gln Glu
5685 5690 5695
Arg Leu Thr Thr Tyr Lys Asp Thr Ala His Thr Glu Ala Met His Ala
5700 5705 5710
Ser Met His Thr Asn Thr Ala Val Ala Asn Val Gly Thr Ser Ile Ser
5715 5720 5725
Gly His Glu Ser Gln Ser Ser Val Pro Ala Asp Ser His Thr Ser Lys
5730 5735 5740
Ala Thr Ser Pro Met Gly Ile Thr Phe Ala Met Gly Asp Thr Ser Val
5745 5750 5755 5760
Ser Thr Ser Thr Pro Ala Phe Phe Glu Thr Arg Ile Gln Thr Glu Ser
5765 5770 5775
Thr Ser Ser Leu Ile Pro Gly Leu Arg Asp Thr Arg Thr Ser Glu Glu
5780 5785 5790
Ile Asn Thr Val Thr Glu Thr Ser Thr Val Leu Ser Glu Val Pro Thr
5795 5800 5805
Thr Thr Thr Thr Glu Val Ser Arg Thr Glu Val Ile Thr Ser Ser Arg
5810 5815 5820
Thr Thr Ile Ser Gly Pro Asp His Ser Lys Met Ser Pro Tyr Ile Ser
5825 5830 5835 5840
Thr Glu Thr Ile Thr Arg Leu Ser Thr Phe Pro Phe Val Thr Gly Ser
5845 5850 5855
Thr Glu Met Ala Ile Thr Asn Gln Thr Gly Pro Ile Gly Thr Ile Ser
5860 5865 5870
Gln Ala Thr Leu Thr Leu Asp Thr Ser Ser Thr Ala Ser Trp Glu Gly
5875 5880 5885
Thr His Ser Pro Val Thr Gln Arg Phe Pro His Ser Glu Glu Thr Thr
5890 5895 5900
Thr Met Ser Arg Ser Thr Lys Gly Val Ser Trp Gln Ser Pro Pro Ser
5905 5910 5915 5920
Val Glu Glu Thr Ser Ser Pro Ser Ser Pro Val Pro Leu Pro Ala Ile
5925 5930 5935
Thr Ser His Ser Ser Leu Tyr Ser Ala Val Ser Gly Ser Ser Pro Thr
5940 5945 5950
Ser Ala Leu Pro Val Thr Ser Leu Leu Thr Ser Gly Arg Arg Lys Thr
5955 5960 5965
Ile Asp Met Leu Asp Thr His Ser Glu Leu Val Thr Ser Ser Leu Pro
5970 5975 5980
Ser Ala Ser Ser Phe Ser Gly Glu Ile Leu Thr Ser Glu Ala Ser Thr
5985 5990 5995 6000
Asn Thr Glu Thr Ile His Phe Ser Glu Asn Thr Ala Glu Thr Asn Met
6005 6010 6015
Gly Thr Thr Asn Ser Met His Lys Leu His Ser Ser Val Ser Ile His
6020 6025 6030
Ser Gln Pro Ser Gly His Thr Pro Pro Lys Val Thr Gly Ser Met Met
6035 6040 6045
Glu Asp Ala Ile Val Ser Thr Ser Thr Pro Gly Ser Pro Glu Thr Lys
6050 6055 6060
Asn Val Asp Arg Asp Ser Thr Ser Pro Leu Thr Pro Glu Leu Lys Glu
6065 6070 6075 6080
Asp Ser Thr Ala Leu Val Met Asn Ser Thr Thr Glu Ser Asn Thr Val
6085 6090 6095
Phe Ser Ser Val Ser Leu Asp Ala Ala Thr Glu Val Ser Arg Ala Glu
6100 6105 6110
Val Thr Tyr Tyr Asp Pro Thr Phe Met Pro Ala Ser Ala Gln Ser Thr
6115 6120 6125
Lys Ser Pro Asp Ile Ser Pro Glu Ala Ser Ser Ser His Ser Asn Ser
6130 6135 6140
Pro Pro Leu Thr Ile Ser Thr His Lys Thr Ile Ala Thr Gln Thr Gly
6145 6150 6155 6160
Pro Ser Gly Val Thr Ser Leu Gly Gln Leu Thr Leu Asp Thr Ser Thr
6165 6170 6175
Ile Ala Thr Ser Ala Gly Thr Pro Ser Ala Arg Thr Gln Asp Phe Val
6180 6185 6190
Asp Ser Glu Thr Thr Ser Val Met Asn Asn Asp Leu Asn Asp Val Leu
6195 6200 6205
Lys Thr Ser Pro Phe Ser Ala Glu Glu Ala Asn Ser Leu Ser Ser Gln
6210 6215 6220
Ala Pro Leu Leu Val Thr Thr Ser Pro Ser Pro Val Thr Ser Thr Leu
6225 6230 6235 6240
Gln Glu His Ser Thr Ser Ser Leu Val Ser Val Thr Ser Val Pro Thr
6245 6250 6255
Pro Thr Leu Ala Lys Ile Thr Asp Met Asp Thr Asn Leu Glu Pro Val
6260 6265 6270
Thr Arg Ser Pro Gln Asn Leu Arg Asn Thr Leu Ala Thr Ser Glu Ala
6275 6280 6285
Thr Thr Asp Thr His Thr Met His Pro Ser Ile Asn Thr Ala Val Ala
6290 6295 6300
Asn Val Gly Thr Thr Ser Ser Pro Asn Glu Phe Tyr Phe Thr Val Ser
6305 6310 6315 6320
Pro Asp Ser Asp Pro Tyr Lys Ala Thr Ser Ala Val Val Ile Thr Ser
6325 6330 6335
Thr Ser Gly Asp Ser Ile Val Ser Thr Ser Met Pro Arg Ser Ser Ala
6340 6345 6350
Met Lys Lys Ile Glu Ser Glu Thr Thr Phe Ser Leu Ile Phe Arg Leu
6355 6360 6365
Arg Glu Thr Ser Thr Ser Gln Lys Ile Gly Ser Ser Ser Asp Thr Ser
6370 6375 6380
Thr Val Phe Asp Lys Ala Phe Thr Ala Ala Thr Thr Glu Val Ser Arg
6385 6390 6395 6400
Thr Glu Leu Thr Ser Ser Ser Arg Thr Ser Ile Gln Gly Thr Glu Lys
6405 6410 6415
Pro Thr Met Ser Pro Asp Thr Ser Thr Arg Ser Val Thr Met Leu Ser
6420 6425 6430
Thr Phe Ala Gly Leu Thr Lys Ser Glu Glu Arg Thr Ile Ala Thr Gln
6435 6440 6445
Thr Gly Pro His Arg Ala Thr Ser Gln Gly Thr Leu Thr Trp Asp Thr
6450 6455 6460
Ser Ile Thr Thr Ser Gln Ala Gly Thr His Ser Ala Met Thr His Gly
6465 6470 6475 6480
Phe Ser Gln Leu Asp Leu Ser Thr Leu Thr Ser Arg Val Pro Glu Tyr
6485 6490 6495
Ile Ser Gly Thr Ser Pro Pro Ser Val Glu Lys Thr Ser Ser Ser Ser
6500 6505 6510
Ser Leu Leu Ser Leu Pro Ala Ile Thr Ser Pro Ser Pro Val Pro Thr
6515 6520 6525
Thr Leu Pro Glu Ser Arg Pro Ser Ser Pro Val His Leu Thr Ser Leu
6530 6535 6540
Pro Thr Ser Gly Leu Val Lys Thr Thr Asp Met Leu Ala Ser Val Ala
6545 6550 6555 6560
Ser Leu Pro Pro Asn Leu Gly Ser Thr Ser His Lys Ile Pro Thr Thr
6565 6570 6575
Ser Glu Asp Ile Lys Asp Thr Glu Lys Met Tyr Pro Ser Thr Asn Ile
6580 6585 6590
Ala Val Thr Asn Val Gly Thr Thr Thr Ser Glu Lys Glu Ser Tyr Ser
6595 6600 6605
Ser Val Pro Ala Tyr Ser Glu Pro Pro Lys Val Thr Ser Pro Met Val
6610 6615 6620
Thr Ser Phe Asn Ile Arg Asp Thr Ile Val Ser Thr Ser Met Pro Gly
6625 6630 6635 6640
Ser Ser Glu Ile Thr Arg Ile Glu Met Glu Ser Thr Phe Ser Leu Ala
6645 6650 6655
His Gly Leu Lys Gly Thr Ser Thr Ser Gln Asp Pro Ile Val Ser Thr
6660 6665 6670
Glu Lys Ser Ala Val Leu His Lys Leu Thr Thr Gly Ala Thr Glu Thr
6675 6680 6685
Ser Arg Thr Glu Val Ala Ser Ser Arg Arg Thr Ser Ile Pro Gly Pro
6690 6695 6700
Asp His Ser Thr Glu Ser Pro Asp Ile Ser Thr Glu Val Ile Pro Ser
6705 6710 6715 6720
Leu Pro Ile Ser Leu Gly Ile Thr Glu Ser Ser Asn Met Thr Ile Ile
6725 6730 6735
Thr Arg Thr Gly Pro Pro Leu Gly Ser Thr Ser Gln Gly Thr Phe Thr
6740 6745 6750
Leu Asp Thr Pro Thr Thr Ser Ser Arg Ala Gly Thr His Ser Met Ala
6755 6760 6765
Thr Gln Glu Phe Pro His Ser Glu Met Thr Thr Val Met Asn Lys Asp
6770 6775 6780
Pro Glu Ile Leu Ser Trp Thr Ile Pro Pro Ser Ile Glu Lys Thr Ser
6785 6790 6795 6800
Phe Ser Ser Ser Leu Met Pro Ser Pro Ala Met Thr Ser Pro Pro Val
6805 6810 6815
Ser Ser Thr Leu Pro Lys Thr Ile His Thr Thr Pro Ser Pro Met Thr
6820 6825 6830
Ser Leu Leu Thr Pro Ser Leu Val Met Thr Thr Asp Thr Leu Gly Thr
6835 6840 6845
Ser Pro Glu Pro Thr Thr Ser Ser Pro Pro Asn Leu Ser Ser Thr Ser
6850 6855 6860
His Glu Ile Leu Thr Thr Asp Glu Asp Thr Thr Ala Ile Glu Ala Met
6865 6870 6875 6880
His Pro Ser Thr Ser Thr Ala Ala Thr Asn Val Glu Thr Thr Ser Ser
6885 6890 6895
Gly His Gly Ser Gln Ser Ser Val Leu Ala Asp Ser Glu Lys Thr Lys
6900 6905 6910
Ala Thr Ala Pro Met Asp Thr Thr Ser Thr Met Gly His Thr Thr Val
6915 6920 6925
Ser Thr Ser Met Ser Val Ser Ser Glu Thr Thr Lys Ile Lys Arg Glu
6930 6935 6940
Ser Thr Tyr Ser Leu Thr Pro Gly Leu Arg Glu Thr Ser Ile Ser Gln
6945 6950 6955 6960
Asn Ala Ser Phe Ser Thr Asp Thr Ser Ile Val Leu Ser Glu Val Pro
6965 6970 6975
Thr Gly Thr Thr Ala Glu Val Ser Arg Thr Glu Val Thr Ser Ser Gly
6980 6985 6990
Arg Thr Ser Ile Pro Gly Pro Ser Gln Ser Thr Val Leu Pro Glu Ile
6995 7000 7005
Ser Thr Arg Thr Met Thr Arg Leu Phe Ala Ser Pro Thr Met Thr Glu
7010 7015 7020
Ser Ala Glu Met Thr Ile Pro Thr Gln Thr Gly Pro Ser Gly Ser Thr
7025 7030 7035 7040
Ser Gln Asp Thr Leu Thr Leu Asp Thr Ser Thr Thr Lys Ser Gln Ala
7045 7050 7055
Lys Thr His Ser Thr Leu Thr Gln Arg Phe Pro His Ser Glu Met Thr
7060 7065 7070
Thr Leu Met Ser Arg Gly Pro Gly Asp Met Ser Trp Gln Ser Ser Pro
7075 7080 7085
Ser Leu Glu Asn Pro Ser Ser Leu Pro Ser Leu Leu Ser Leu Pro Ala
7090 7095 7100
Thr Thr Ser Pro Pro Pro Ile Ser Ser Thr Leu Pro Val Thr Ile Ser
7105 7110 7115 7120
Ser Ser Pro Leu Pro Val Thr Ser Leu Leu Thr Ser Ser Pro Val Thr
7125 7130 7135
Thr Thr Asp Met Leu His Thr Ser Pro Glu Leu Val Thr Ser Ser Pro
7140 7145 7150
Pro Lys Leu Ser His Thr Ser Asp Glu Arg Leu Thr Thr Gly Lys Asp
7155 7160 7165
Thr Thr Asn Thr Glu Ala Val His Pro Ser Thr Asn Thr Ala Ala Ser
7170 7175 7180
Asn Val Glu Ile Pro Ser Ser Gly His Glu Ser Pro Ser Ser Ala Leu
7185 7190 7195 7200
Ala Asp Ser Glu Thr Ser Lys Ala Thr Ser Pro Met Phe Ile Thr Ser
7205 7210 7215
Thr Gln Glu Asp Thr Thr Val Ala Ile Ser Thr Pro His Phe Leu Glu
7220 7225 7230
Thr Ser Arg Ile Gln Lys Glu Ser Ile Ser Ser Leu Ser Pro Lys Leu
7235 7240 7245
Arg Glu Thr Gly Ser Ser Val Glu Thr Ser Ser Ala Ile Glu Thr Ser
7250 7255 7260
Ala Val Leu Ser Glu Val Ser Ile Gly Ala Thr Thr Glu Ile Ser Arg
7265 7270 7275 7280
Thr Glu Val Thr Ser Ser Ser Arg Thr Ser Ile Ser Gly Ser Ala Glu
7285 7290 7295
Ser Thr Met Leu Pro Glu Ile Ser Thr Thr Arg Lys Ile Ile Lys Phe
7300 7305 7310
Pro Thr Ser Pro Ile Leu Ala Glu Ser Ser Glu Met Thr Ile Lys Thr
7315 7320 7325
Gln Thr Ser Pro Pro Gly Ser Thr Ser Glu Ser Thr Phe Thr Leu Asp
7330 7335 7340
Thr Ser Thr Thr Pro Ser Leu Val Ile Thr His Ser Thr Met Thr Gln
7345 7350 7355 7360
Arg Leu Pro His Ser Glu Ile Thr Thr Leu Val Ser Arg Gly Ala Gly
7365 7370 7375
Asp Val Pro Arg Pro Ser Ser Leu Pro Val Glu Glu Thr Ser Pro Pro
7380 7385 7390
Ser Ser Gln Leu Ser Leu Ser Ala Met Ile Ser Pro Ser Pro Val Ser
7395 7400 7405
Ser Thr Leu Pro Ala Ser Ser His Ser Ser Ser Ala Ser Val Thr Ser
7410 7415 7420
Leu Leu Thr Pro Gly Gln Val Lys Thr Thr Glu Val Leu Asp Ala Ser
7425 7430 7435 7440
Ala Glu Pro Glu Thr Ser Ser Pro Pro Ser Leu Ser Ser Thr Ser Val
7445 7450 7455
Glu Ile Leu Ala Thr Ser Glu Val Thr Thr Asp Thr Glu Lys Ile His
7460 7465 7470
Pro Phe Ser Asn Thr Ala Val Thr Lys Val Gly Thr Ser Ser Ser Gly
7475 7480 7485
His Glu Ser Pro Ser Ser Val Leu Pro Asp Ser Glu Thr Thr Lys Ala
7490 7495 7500
Thr Ser Ala Met Gly Thr Ile Ser Ile Met Gly Asp Thr Ser Val Ser
7505 7510 7515 7520
Thr Leu Thr Pro Ala Leu Ser Asn Thr Arg Lys Ile Gln Ser Glu Pro
7525 7530 7535
Ala Ser Ser Leu Thr Thr Arg Leu Arg Glu Thr Ser Thr Ser Glu Glu
7540 7545 7550
Thr Ser Leu Ala Thr Glu Ala Asn Thr Val Leu Ser Lys Val Ser Thr
7555 7560 7565
Gly Ala Thr Thr Glu Val Ser Arg Thr Glu Ala Ile Ser Phe Ser Arg
7570 7575 7580
Thr Ser Met Ser Gly Pro Glu Gln Ser Thr Met Ser Gln Asp Ile Ser
7585 7590 7595 7600
Ile Gly Thr Ile Pro Arg Ile Ser Ala Ser Ser Val Leu Thr Glu Ser
7605 7610 7615
Ala Lys Met Thr Ile Thr Thr Gln Thr Gly Pro Ser Glu Ser Thr Leu
7620 7625 7630
Glu Ser Thr Leu Asn Leu Asn Thr Ala Thr Thr Pro Ser Trp Val Glu
7635 7640 7645
Thr His Ser Ile Val Ile Gln Gly Phe Pro His Pro Glu Met Thr Thr
7650 7655 7660
Ser Met Gly Arg Gly Pro Gly Gly Val Ser Trp Pro Ser Pro Pro Phe
7665 7670 7675 7680
Val Lys Glu Thr Ser Pro Pro Ser Ser Pro Leu Ser Leu Pro Ala Val
7685 7690 7695
Thr Ser Pro His Pro Val Ser Thr Thr Phe Leu Ala His Ile Pro Pro
7700 7705 7710
Ser Pro Leu Pro Val Thr Ser Leu Leu Thr Ser Gly Pro Ala Thr Thr
7715 7720 7725
Thr Asp Ile Leu Gly Thr Ser Thr Glu Pro Gly Thr Ser Ser Ser Ser
7730 7735 7740
Ser Leu Ser Thr Thr Ser His Glu Arg Leu Thr Thr Tyr Lys Asp Thr
7745 7750 7755 7760
Ala His Thr Glu Ala Val His Pro Ser Thr Asn Thr Gly Gly Thr Asn
7765 7770 7775
Val Ala Thr Thr Ser Ser Gly Tyr Lys Ser Gln Ser Ser Val Leu Ala
7780 7785 7790
Asp Ser Ser Pro Met Cys Thr Thr Ser Thr Met Gly Asp Thr Ser Val
7795 7800 7805
Leu Thr Ser Thr Pro Ala Phe Leu Glu Thr Arg Arg Ile Gln Thr Glu
7810 7815 7820
Leu Ala Ser Ser Leu Thr Pro Gly Leu Arg Glu Ser Ser Gly Ser Glu
7825 7830 7835 7840
Gly Thr Ser Ser Gly Thr Lys Met Ser Thr Val Leu Ser Lys Val Pro
7845 7850 7855
Thr Gly Ala Thr Thr Glu Ile Ser Lys Glu Asp Val Thr Ser Ile Pro
7860 7865 7870
Gly Pro Ala Gln Ser Thr Ile Ser Pro Asp Ile Ser Thr Arg Thr Val
7875 7880 7885
Ser Trp Phe Ser Thr Ser Pro Val Met Thr Glu Ser Ala Glu Ile Thr
7890 7895 7900
Met Asn Thr His Thr Ser Pro Leu Gly Ala Thr Thr Gln Gly Thr Ser
7905 7910 7915 7920
Thr Leu Asp Thr Ser Ser Thr Thr Ser Leu Thr Met Thr His Ser Thr
7925 7930 7935
Ile Ser Gln Gly Phe Ser His Ser Gln Met Ser Thr Leu Met Arg Arg
7940 7945 7950
Gly Pro Glu Asp Val Ser Trp Met Ser Pro Pro Leu Leu Glu Lys Thr
7955 7960 7965
Arg Pro Ser Phe Ser Leu Met Ser Ser Pro Ala Thr Thr Ser Pro Ser
7970 7975 7980
Pro Val Ser Ser Thr Leu Pro Glu Ser Ile Ser Ser Ser Pro Leu Pro
7985 7990 7995 8000
Val Thr Ser Leu Leu Thr Ser Gly Leu Ala Lys Thr Thr Asp Met Leu
8005 8010 8015
His Lys Ser Ser Glu Pro Val Thr Asn Ser Pro Ala Asn Leu Ser Ser
8020 8025 8030
Thr Ser Val Glu Ile Leu Ala Thr Ser Glu Val Thr Thr Asp Thr Glu
8035 8040 8045
Lys Thr His Pro Ser Ser Asn Arg Thr Val Thr Asp Val Gly Thr Ser
8050 8055 8060
Ser Ser Gly His Glu Ser Thr Ser Phe Val Leu Ala Asp Ser Gln Thr
8065 8070 8075 8080
Ser Lys Val Thr Ser Pro Met Val Ile Thr Ser Thr Met Glu Asp Thr
8085 8090 8095
Ser Val Ser Thr Ser Thr Pro Gly Phe Phe Glu Thr Ser Arg Ile Gln
8100 8105 8110
Thr Glu Pro Thr Ser Ser Leu Thr Leu Gly Leu Arg Lys Thr Ser Ser
8115 8120 8125
Ser Glu Gly Thr Ser Leu Ala Thr Glu Met Ser Thr Val Leu Ser Gly
8130 8135 8140
Val Pro Thr Gly Ala Thr Ala Glu Val Ser Arg Thr Glu Val Thr Ser
8145 8150 8155 8160
Ser Ser Arg Thr Ser Ile Ser Gly Phe Ala Gln Leu Thr Val Ser Pro
8165 8170 8175
Glu Thr Ser Thr Glu Thr Ile Thr Arg Leu Pro Thr Ser Ser Ile Met
8180 8185 8190
Thr Glu Ser Ala Glu Met Met Ile Lys Thr Gln Thr Asp Pro Pro Gly
8195 8200 8205
Ser Thr Pro Glu Ser Thr His Thr Val Asp Ile Ser Thr Thr Pro Asn
8210 8215 8220
Trp Val Glu Thr His Ser Thr Val Thr Gln Arg Phe Ser His Ser Glu
8225 8230 8235 8240
Met Thr Thr Leu Val Ser Arg Ser Pro Gly Asp Met Leu Trp Pro Ser
8245 8250 8255
Gln Ser Ser Val Glu Glu Thr Ser Ser Ala Ser Ser Leu Leu Ser Leu
8260 8265 8270
Pro Ala Thr Thr Ser Pro Ser Pro Val Ser Ser Thr Leu Val Glu Asp
8275 8280 8285
Phe Pro Ser Ala Ser Leu Pro Val Thr Ser Leu Leu Asn Pro Gly Leu
8290 8295 8300
Val Ile Thr Thr Asp Arg Met Gly Ile Ser Arg Glu Pro Gly Thr Ser
8305 8310 8315 8320
Ser Thr Ser Asn Leu Ser Ser Thr Ser His Glu Arg Leu Thr Thr Leu
8325 8330 8335
Glu Asp Thr Val Asp Thr Glu Asp Met Gln Pro Ser Thr His Thr Ala
8340 8345 8350
Val Thr Asn Val Arg Thr Ser Ile Ser Gly His Glu Ser Gln Ser Ser
8355 8360 8365
Val Leu Ser Asp Ser Glu Thr Pro Lys Ala Thr Ser Pro Met Gly Thr
8370 8375 8380
Thr Tyr Thr Met Gly Glu Thr Ser Val Ser Ile Ser Thr Ser Asp Phe
8385 8390 8395 8400
Phe Glu Thr Ser Arg Ile Gln Ile Glu Pro Thr Ser Ser Leu Thr Ser
8405 8410 8415
Gly Leu Arg Glu Thr Ser Ser Ser Glu Arg Ile Ser Ser Ala Thr Glu
8420 8425 8430
Gly Ser Thr Val Leu Ser Glu Val Pro Ser Gly Ala Thr Thr Glu Val
8435 8440 8445
Ser Arg Thr Glu Val Ile Ser Ser Arg Gly Thr Ser Met Ser Gly Pro
8450 8455 8460
Asp Gln Phe Thr Ile Ser Pro Asp Ile Ser Thr Glu Ala Ile Thr Arg
8465 8470 8475 8480
Leu Ser Thr Ser Pro Ile Met Thr Glu Ser Ala Glu Ser Ala Ile Thr
8485 8490 8495
Ile Glu Thr Gly Ser Pro Gly Ala Thr Ser Glu Gly Thr Leu Thr Leu
8500 8505 8510
Asp Thr Ser Thr Thr Thr Phe Trp Ser Gly Thr His Ser Thr Ala Ser
8515 8520 8525
Pro Gly Phe Ser His Ser Glu Met Thr Thr Leu Met Ser Arg Thr Pro
8530 8535 8540
Gly Asp Val Pro Trp Pro Ser Leu Pro Ser Val Glu Glu Ala Ser Ser
8545 8550 8555 8560
Val Ser Ser Ser Leu Ser Ser Pro Ala Met Thr Ser Thr Ser Phe Phe
8565 8570 8575
Ser Thr Leu Pro Glu Ser Ile Ser Ser Ser Pro His Pro Val Thr Ala
8580 8585 8590
Leu Leu Thr Leu Gly Pro Val Lys Thr Thr Asp Met Leu Arg Thr Ser
8595 8600 8605
Ser Glu Pro Glu Thr Ser Ser Pro Pro Asn Leu Ser Ser Thr Ser Ala
8610 8615 8620
Glu Ile Leu Ala Thr Ser Glu Val Thr Lys Asp Arg Glu Lys Ile His
8625 8630 8635 8640
Pro Ser Ser Asn Thr Pro Val Val Asn Val Gly Thr Val Ile Tyr Lys
8645 8650 8655
His Leu Ser Pro Ser Ser Val Leu Ala Asp Leu Val Thr Thr Lys Pro
8660 8665 8670
Thr Ser Pro Met Ala Thr Thr Ser Thr Leu Gly Asn Thr Ser Val Ser
8675 8680 8685
Thr Ser Thr Pro Ala Phe Pro Glu Thr Met Met Thr Gln Pro Thr Ser
8690 8695 8700
Ser Leu Thr Ser Gly Leu Arg Glu Ile Ser Thr Ser Gln Glu Thr Ser
8705 8710 8715 8720
Ser Ala Thr Glu Arg Ser Ala Ser Leu Ser Gly Met Pro Thr Gly Ala
8725 8730 8735
Thr Thr Lys Val Ser Arg Thr Glu Ala Leu Ser Leu Gly Arg Thr Ser
8740 8745 8750
Thr Pro Gly Pro Ala Gln Ser Thr Ile Ser Pro Glu Ile Ser Thr Glu
8755 8760 8765
Thr Ile Thr Arg Ile Ser Thr Pro Leu Thr Thr Thr Gly Ser Ala Glu
8770 8775 8780
Met Thr Ile Thr Pro Lys Thr Gly His Ser Gly Ala Ser Ser Gln Gly
8785 8790 8795 8800
Thr Phe Thr Leu Asp Thr Ser Ser Arg Ala Ser Trp Pro Gly Thr His
8805 8810 8815
Ser Ala Ala Thr His Arg Ser Pro His Ser Gly Met Thr Thr Pro Met
8820 8825 8830
Ser Arg Gly Pro Glu Asp Val Ser Trp Pro Ser Arg Pro Ser Val Glu
8835 8840 8845
Lys Thr Ser Pro Pro Ser Ser Leu Val Ser Leu Ser Ala Val Thr Ser
8850 8855 8860
Pro Ser Pro Leu Tyr Ser Thr Pro Ser Glu Ser Ser His Ser Ser Pro
8865 8870 8875 8880
Leu Arg Val Thr Ser Leu Phe Thr Pro Val Met Met Lys Thr Thr Asp
8885 8890 8895
Met Leu Asp Thr Ser Leu Glu Pro Val Thr Thr Ser Pro Pro Ser Met
8900 8905 8910
Asn Ile Thr Ser Asp Glu Ser Leu Ala Thr Ser Lys Ala Thr Met Glu
8915 8920 8925
Thr Glu Ala Ile Gln Leu Ser Glu Asn Thr Ala Val Thr Gln Met Gly
8930 8935 8940
Thr Ile Ser Ala Arg Gln Glu Phe Tyr Ser Ser Tyr Pro Gly Leu Pro
8945 8950 8955 8960
Glu Pro Ser Lys Val Thr Ser Pro Val Val Thr Ser Ser Thr Ile Lys
8965 8970 8975
Asp Ile Val Ser Thr Thr Ile Pro Ala Ser Ser Glu Ile Thr Arg Ile
8980 8985 8990
Glu Met Glu Ser Thr Ser Thr Leu Thr Pro Thr Pro Arg Glu Thr Ser
8995 9000 9005
Thr Ser Gln Glu Ile His Ser Ala Thr Lys Pro Ser Thr Val Pro Tyr
9010 9015 9020
Lys Ala Leu Thr Ser Ala Thr Ile Glu Asp Ser Met Thr Gln Val Met
9025 9030 9035 9040
Ser Ser Ser Arg Gly Pro Ser Pro Asp Gln Ser Thr Met Ser Gln Asp
9045 9050 9055
Ile Ser Thr Glu Val Ile Thr Arg Leu Ser Thr Ser Pro Ile Lys Thr
9060 9065 9070
Glu Ser Thr Glu Met Thr Ile Thr Thr Gln Thr Gly Ser Pro Gly Ala
9075 9080 9085
Thr Ser Arg Gly Thr Leu Thr Leu Asp Thr Ser Thr Thr Phe Met Ser
9090 9095 9100
Gly Thr His Ser Thr Ala Ser Gln Gly Phe Ser His Ser Gln Met Thr
9105 9110 9115 9120
Ala Leu Met Ser Arg Thr Pro Gly Asp Val Pro Trp Leu Ser His Pro
9125 9130 9135
Ser Val Glu Glu Ala Ser Ser Ala Ser Phe Ser Leu Ser Ser Pro Val
9140 9145 9150
Met Thr Ser Ser Ser Pro Val Ser Ser Thr Leu Pro Asp Ser Ile His
9155 9160 9165
Ser Ser Ser Leu Pro Val Thr Ser Leu Leu Thr Ser Gly Leu Val Lys
9170 9175 9180
Thr Thr Glu Leu Leu Gly Thr Ser Ser Glu Pro Glu Thr Ser Ser Pro
9185 9190 9195 9200
Pro Asn Leu Ser Ser Thr Ser Ala Glu Ile Leu Ala Ile Thr Glu Val
9205 9210 9215
Thr Thr Asp Thr Glu Lys Leu Glu Met Thr Asn Val Val Thr Ser Gly
9220 9225 9230
Tyr Thr His Glu Ser Pro Ser Ser Val Leu Ala Asp Ser Val Thr Thr
9235 9240 9245
Lys Ala Thr Ser Ser Met Gly Ile Thr Tyr Pro Thr Gly Asp Thr Asn
9250 9255 9260
Val Leu Thr Ser Thr Pro Ala Phe Ser Asp Thr Ser Arg Ile Gln Thr
9265 9270 9275 9280
Lys Ser Lys Leu Ser Leu Thr Pro Gly Leu Met Glu Thr Ser Ile Ser
9285 9290 9295
Glu Glu Thr Ser Ser Ala Thr Glu Lys Ser Thr Val Leu Ser Ser Val
9300 9305 9310
Pro Thr Gly Ala Thr Thr Glu Val Ser Arg Thr Glu Ala Ile Ser Ser
9315 9320 9325
Ser Arg Thr Ser Ile Pro Gly Pro Ala Gln Ser Thr Met Ser Ser Asp
9330 9335 9340
Thr Ser Met Glu Thr Ile Thr Arg Ile Ser Thr Pro Leu Thr Arg Lys
9345 9350 9355 9360
Glu Ser Thr Asp Met Ala Ile Thr Pro Lys Thr Gly Pro Ser Gly Ala
9365 9370 9375
Thr Ser Gln Gly Thr Phe Thr Leu Asp Ser Ser Ser Thr Ala Ser Trp
9380 9385 9390
Pro Gly Thr His Ser Ala Thr Thr Gln Arg Phe Pro Gln Ser Val Val
9395 9400 9405
Thr Thr Pro Met Ser Arg Gly Pro Glu Asp Val Ser Trp Pro Ser Pro
9410 9415 9420
Leu Ser Val Glu Lys Asn Ser Pro Pro Ser Ser Leu Val Ser Ser Ser
9425 9430 9435 9440
Ser Val Thr Ser Pro Ser Pro Leu Tyr Ser Thr Pro Ser Gly Ser Ser
9445 9450 9455
His Ser Ser Pro Val Pro Val Thr Ser Leu Phe Thr Ser Ile Met Met
9460 9465 9470
Lys Ala Thr Asp Met Leu Asp Ala Ser Leu Glu Pro Glu Thr Thr Ser
9475 9480 9485
Ala Pro Asn Met Asn Ile Thr Ser Asp Glu Ser Leu Ala Ala Ser Lys
9490 9495 9500
Ala Thr Thr Glu Thr Glu Ala Ile His Val Phe Glu Asn Thr Ala Ala
9505 9510 9515 9520
Ser His Val Glu Thr Thr Ser Ala Thr Glu Glu Leu Tyr Ser Ser Ser
9525 9530 9535
Pro Gly Phe Ser Glu Pro Thr Lys Val Ile Ser Pro Val Val Thr Ser
9540 9545 9550
Ser Ser Ile Arg Asp Asn Met Val Ser Thr Thr Met Pro Gly Ser Ser
9555 9560 9565
Gly Ile Thr Arg Ile Glu Ile Glu Ser Met Ser Ser Leu Thr Pro Gly
9570 9575 9580
Leu Arg Glu Thr Arg Thr Ser Gln Asp Ile Thr Ser Ser Thr Glu Thr
9585 9590 9595 9600
Ser Thr Val Leu Tyr Lys Met Pro Ser Gly Ala Thr Pro Glu Val Ser
9605 9610 9615
Arg Thr Glu Val Met Pro Ser Ser Arg Thr Ser Ile Pro Gly Pro Ala
9620 9625 9630
Gln Ser Thr Met Ser Leu Asp Ile Ser Asp Glu Val Val Thr Arg Leu
9635 9640 9645
Ser Thr Ser Pro Ile Met Thr Glu Ser Ala Glu Ile Thr Ile Thr Thr
9650 9655 9660
Gln Thr Gly Tyr Ser Leu Ala Thr Ser Gln Val Thr Leu Pro Leu Gly
9665 9670 9675 9680
Thr Ser Met Thr Phe Leu Ser Gly Thr His Ser Thr Met Ser Gln Gly
9685 9690 9695
Leu Ser His Ser Glu Met Thr Asn Leu Met Ser Arg Gly Pro Glu Ser
9700 9705 9710
Leu Ser Trp Thr Ser Pro Arg Phe Val Glu Thr Thr Arg Ser Ser Ser
9715 9720 9725
Ser Leu Thr Ser Leu Pro Leu Thr Thr Ser Leu Ser Pro Val Ser Ser
9730 9735 9740
Thr Leu Leu Asp Ser Ser Pro Ser Ser Pro Leu Pro Val Thr Ser Leu
9745 9750 9755 9760
Ile Leu Pro Gly Leu Val Lys Thr Thr Glu Val Leu Asp Thr Ser Ser
9765 9770 9775
Glu Pro Lys Thr Ser Ser Ser Pro Asn Leu Ser Ser Thr Ser Val Glu
9780 9785 9790
Ile Pro Ala Thr Ser Glu Ile Met Thr Asp Thr Glu Lys Ile His Pro
9795 9800 9805
Ser Ser Asn Thr Ala Val Ala Lys Val Arg Thr Ser Ser Ser Val His
9810 9815 9820
Glu Ser His Ser Ser Val Leu Ala Asp Ser Glu Thr Thr Ile Thr Ile
9825 9830 9835 9840
Pro Ser Met Gly Ile Thr Ser Ala Val Asp Asp Thr Thr Val Phe Thr
9845 9850 9855
Ser Asn Pro Ala Phe Ser Glu Thr Arg Arg Ile Pro Thr Glu Pro Thr
9860 9865 9870
Phe Ser Leu Thr Pro Gly Phe Arg Glu Thr Ser Thr Ser Glu Glu Thr
9875 9880 9885
Thr Ser Ile Thr Glu Thr Ser Ala Val Leu Tyr Gly Val Pro Thr Ser
9890 9895 9900
Ala Thr Thr Glu Val Ser Met Thr Glu Ile Met Ser Ser Asn Arg Ile
9905 9910 9915 9920
His Ile Pro Asp Ser Asp Gln Ser Thr Met Ser Pro Asp Ile Ile Thr
9925 9930 9935
Glu Val Ile Thr Arg Leu Ser Ser Ser Ser Met Met Ser Glu Ser Thr
9940 9945 9950
Gln Met Thr Ile Thr Thr Gln Lys Ser Ser Pro Gly Ala Thr Ala Gln
9955 9960 9965
Ser Thr Leu Thr Leu Ala Thr Thr Thr Ala Pro Leu Ala Arg Thr His
9970 9975 9980
Ser Thr Val Pro Pro Arg Phe Leu His Ser Glu Met Thr Thr Leu Met
9985 9990 9995 10000
Ser Arg Ser Pro Glu Asn Pro Ser Trp Lys Ser Ser Leu Phe Val Glu
10005 10010 10015
Lys Thr Ser Ser Ser Ser Ser Leu Leu Ser Leu Pro Val Thr Thr Ser
10020 10025 10030
Pro Ser Val Ser Ser Thr Leu Pro Gln Ser Ile Pro Ser Ser Ser Phe
10035 10040 10045
Ser Val Thr Ser Leu Leu Thr Pro Gly Met Val Lys Thr Thr Asp Thr
10050 10055 10060
Ser Thr Glu Pro Gly Thr Ser Leu Ser Pro Asn Leu Ser Gly Thr Ser
10065 10070 10075 10080
Val Glu Ile Leu Ala Ala Ser Glu Val Thr Thr Asp Thr Glu Lys Ile
10085 10090 10095
His Pro Ser Ser Ser Met Ala Val Thr Asn Val Gly Thr Thr Ser Ser
10100 10105 10110
Gly His Glu Leu Tyr Ser Ser Val Ser Ile His Ser Glu Pro Ser Lys
10115 10120 10125
Ala Thr Tyr Pro Val Gly Thr Pro Ser Ser Met Ala Glu Thr Ser Ile
10130 10135 10140
Ser Thr Ser Met Pro Ala Asn Phe Glu Thr Thr Gly Phe Glu Ala Glu
10145 10150 10155 10160
Pro Phe Ser His Leu Thr Ser Gly Phe Arg Lys Thr Asn Met Ser Leu
10165 10170 10175
Asp Thr Ser Ser Val Thr Pro Thr Asn Thr Pro Ser Ser Pro Gly Ser
10180 10185 10190
Thr His Leu Leu Gln Ser Ser Lys Thr Asp Phe Thr Ser Ser Ala Lys
10195 10200 10205
Thr Ser Ser Pro Asp Trp Pro Pro Ala Ser Gln Tyr Thr Glu Ile Pro
10210 10215 10220
Val Asp Ile Ile Thr Pro Phe Asn Ala Ser Pro Ser Ile Thr Glu Ser
10225 10230 10235 10240
Thr Gly Ile Thr Ser Phe Pro Glu Ser Arg Phe Thr Met Ser Val Thr
10245 10250 10255
Glu Ser Thr His His Leu Ser Thr Asp Leu Leu Pro Ser Ala Glu Thr
10260 10265 10270
Ile Ser Thr Gly Thr Val Met Pro Ser Leu Ser Glu Ala Met Thr Ser
10275 10280 10285
Phe Ala Thr Thr Gly Val Pro Arg Ala Ile Ser Gly Ser Gly Ser Pro
10290 10295 10300
Phe Ser Arg Thr Glu Ser Gly Pro Gly Asp Ala Thr Leu Ser Thr Ile
10305 10310 10315 10320
Ala Glu Ser Leu Pro Ser Ser Thr Pro Val Pro Phe Ser Ser Ser Thr
10325 10330 10335
Phe Thr Thr Thr Asp Ser Ser Thr Ile Pro Ala Leu His Glu Ile Thr
10340 10345 10350
Ser Ser Ser Ala Thr Pro Tyr Arg Val Asp Thr Ser Leu Gly Thr Glu
10355 10360 10365
Ser Ser Thr Thr Glu Gly Arg Leu Val Met Val Ser Thr Leu Asp Thr
10370 10375 10380
Ser Ser Gln Pro Gly Arg Thr Ser Ser Ser Pro Ile Leu Asp Thr Arg
10385 10390 10395 10400
Met Thr Glu Ser Val Glu Leu Gly Thr Val Thr Ser Ala Tyr Gln Val
10405 10410 10415
Pro Ser Leu Ser Thr Arg Leu Thr Arg Thr Asp Gly Ile Met Glu His
10420 10425 10430
Ile Thr Lys Ile Pro Asn Glu Ala Ala His Arg Gly Thr Ile Arg Pro
10435 10440 10445
Val Lys Gly Pro Gln Thr Ser Thr Ser Pro Ala Ser Pro Lys Gly Leu
10450 10455 10460
His Thr Gly Gly Thr Lys Arg Met Glu Thr Thr Thr Thr Ala Leu Lys
10465 10470 10475 10480
Thr Thr Thr Thr Ala Leu Lys Thr Thr Ser Arg Ala Thr Leu Thr Thr
10485 10490 10495
Ser Val Tyr Thr Pro Thr Leu Gly Thr Leu Thr Pro Leu Asn Ala Ser
10500 10505 10510
Met Gln Met Ala Ser Thr Ile Pro Thr Glu Met Met Ile Thr Thr Pro
10515 10520 10525
Tyr Val Phe Pro Asp Val Pro Glu Thr Thr Ser Ser Leu Ala Thr Ser
10530 10535 10540
Leu Gly Ala Glu Thr Ser Thr Ala Leu Pro Arg Thr Thr Pro Ser Val
10545 10550 10555 10560
Phe Asn Arg Glu Ser Glu Thr Thr Ala Ser Leu Val Ser Arg Ser Gly
10565 10570 10575
Ala Glu Arg Ser Pro Val Ile Gln Thr Leu Asp Val Ser Ser Ser Glu
10580 10585 10590
Pro Asp Thr Thr Ala Ser Trp Val Ile His Pro Ala Glu Thr Ile Pro
10595 10600 10605
Thr Val Ser Lys Thr Thr Pro Asn Phe Phe His Ser Glu Leu Asp Thr
10610 10615 10620
Val Ser Ser Thr Ala Thr Ser His Gly Ala Asp Val Ser Ser Ala Ile
10625 10630 10635 10640
Pro Thr Asn Ile Ser Pro Ser Glu Leu Asp Ala Leu Thr Pro Leu Val
10645 10650 10655
Thr Ile Ser Gly Thr Asp Thr Ser Thr Thr Phe Pro Thr Leu Thr Lys
10660 10665 10670
Ser Pro His Glu Thr Glu Thr Arg Thr Thr Trp Leu Thr His Pro Ala
10675 10680 10685
Glu Thr Ser Ser Thr Ile Pro Arg Thr Ile Pro Asn Phe Ser His His
10690 10695 10700
Glu Ser Asp Ala Thr Pro Ser Ile Ala Thr Ser Pro Gly Ala Glu Thr
10705 10710 10715 10720
Ser Ser Ala Ile Pro Ile Met Thr Val Ser Pro Gly Ala Glu Asp Leu
10725 10730 10735
Val Thr Ser Gln Val Thr Ser Ser Gly Thr Asp Arg Asn Met Thr Ile
10740 10745 10750
Pro Thr Leu Thr Leu Ser Pro Gly Glu Pro Lys Thr Ile Ala Ser Leu
10755 10760 10765
Val Thr His Pro Glu Ala Gln Thr Ser Ser Ala Ile Pro Thr Ser Thr
10770 10775 10780
Ile Ser Pro Ala Val Ser Arg Leu Val Thr Ser Met Val Thr Ser Leu
10785 10790 10795 10800
Ala Ala Lys Thr Ser Thr Thr Asn Arg Ala Leu Thr Asn Ser Pro Gly
10805 10810 10815
Glu Pro Ala Thr Thr Val Ser Leu Val Thr His Pro Ala Gln Thr Ser
10820 10825 10830
Pro Thr Val Pro Trp Thr Thr Ser Ile Phe Phe His Ser Lys Ser Asp
10835 10840 10845
Thr Thr Pro Ser Met Thr Thr Ser His Gly Ala Glu Ser Ser Ser Ala
10850 10855 10860
Val Pro Thr Pro Thr Val Ser Thr Glu Val Pro Gly Val Val Thr Pro
10865 10870 10875 10880
Leu Val Thr Ser Ser Arg Ala Val Ile Ser Thr Thr Ile Pro Ile Leu
10885 10890 10895
Thr Leu Ser Pro Gly Glu Pro Glu Thr Thr Pro Ser Met Ala Thr Ser
10900 10905 10910
His Gly Glu Glu Ala Ser Ser Ala Ile Pro Thr Pro Thr Val Ser Pro
10915 10920 10925
Gly Val Pro Gly Val Val Thr Ser Leu Val Thr Ser Ser Arg Ala Val
10930 10935 10940
Thr Ser Thr Thr Ile Pro Ile Leu Thr Phe Ser Leu Gly Glu Pro Glu
10945 10950 10955 10960
Thr Thr Pro Ser Met Ala Thr Ser His Gly Thr Glu Ala Gly Ser Ala
10965 10970 10975
Val Pro Thr Val Leu Pro Glu Val Pro Gly Met Val Thr Ser Leu Val
10980 10985 10990
Ala Ser Ser Arg Ala Val Thr Ser Thr Thr Leu Pro Thr Leu Thr Leu
10995 11000 11005
Ser Pro Gly Glu Pro Glu Thr Thr Pro Ser Met Ala Thr Ser His Gly
11010 11015 11020
Ala Glu Ala Ser Ser Thr Val Pro Thr Val Ser Pro Glu Val Pro Gly
11025 11030 11035 11040
Val Val Thr Ser Leu Val Thr Ser Ser Ser Gly Val Asn Ser Thr Ser
11045 11050 11055
Ile Pro Thr Leu Ile Leu Ser Pro Gly Glu Leu Glu Thr Thr Pro Ser
11060 11065 11070
Met Ala Thr Ser His Gly Ala Glu Ala Ser Ser Ala Val Pro Thr Pro
11075 11080 11085
Thr Val Ser Pro Gly Val Ser Gly Val Val Thr Pro Leu Val Thr Ser
11090 11095 11100
Ser Arg Ala Val Thr Ser Thr Thr Ile Pro Ile Leu Thr Leu Ser Ser
11105 11110 11115 11120
Ser Glu Pro Glu Thr Thr Pro Ser Met Ala Thr Ser His Gly Val Glu
11125 11130 11135
Ala Ser Ser Ala Val Leu Thr Val Ser Pro Glu Val Pro Gly Met Val
11140 11145 11150
Thr Ser Leu Val Thr Ser Ser Arg Ala Val Thr Ser Thr Thr Ile Pro
11155 11160 11165
Thr Leu Thr Ile Ser Ser Asp Glu Pro Glu Thr Thr Thr Ser Leu Val
11170 11175 11180
Thr His Ser Glu Ala Lys Met Ile Ser Ala Ile Pro Thr Leu Ala Val
11185 11190 11195 11200
Ser Pro Thr Val Gln Gly Leu Val Thr Ser Leu Val Thr Ser Ser Gly
11205 11210 11215
Ser Glu Thr Ser Ala Phe Ser Asn Leu Thr Val Ala Ser Ser Gln Pro
11220 11225 11230
Glu Thr Ile Asp Ser Trp Val Ala His Pro Gly Thr Glu Ala Ser Ser
11235 11240 11245
Val Val Pro Thr Leu Thr Val Ser Thr Gly Glu Pro Phe Thr Asn Ile
11250 11255 11260
Ser Leu Val Thr His Pro Ala Glu Ser Ser Ser Thr Leu Pro Arg Thr
11265 11270 11275 11280
Thr Ser Arg Phe Ser His Ser Glu Leu Asp Thr Met Pro Ser Thr Val
11285 11290 11295
Thr Ser Pro Glu Ala Glu Ser Ser Ser Ala Ile Ser Thr Thr Ile Ser
11300 11305 11310
Pro Gly Ile Pro Gly Val Leu Thr Ser Leu Val Thr Ser Ser Gly Arg
11315 11320 11325
Asp Ile Ser Ala Thr Phe Pro Thr Val Pro Glu Ser Pro His Glu Ser
11330 11335 11340
Glu Ala Thr Ala Ser Trp Val Thr His Pro Ala Val Thr Ser Thr Thr
11345 11350 11355 11360
Val Pro Arg Thr Thr Pro Asn Tyr Ser His Ser Glu Pro Asp Thr Thr
11365 11370 11375
Pro Ser Ile Ala Thr Ser Pro Gly Ala Glu Ala Thr Ser Asp Phe Pro
11380 11385 11390
Thr Ile Thr Val Ser Pro Asp Val Pro Asp Met Val Thr Ser Gln Val
11395 11400 11405
Thr Ser Ser Gly Thr Asp Thr Ser Ile Thr Ile Pro Thr Leu Thr Leu
11410 11415 11420
Ser Ser Gly Glu Pro Glu Thr Thr Thr Ser Phe Ile Thr Tyr Ser Glu
11425 11430 11435 11440
Thr His Thr Ser Ser Ala Ile Pro Thr Leu Pro Val Ser Pro Gly Ala
11445 11450 11455
Ser Lys Met Leu Thr Ser Leu Val Ile Ser Ser Gly Thr Asp Ser Thr
11460 11465 11470
Thr Thr Phe Pro Thr Leu Thr Glu Thr Pro Tyr Glu Pro Glu Thr Thr
11475 11480 11485
Ala Ile Gln Leu Ile His Pro Ala Glu Thr Asn Thr Met Val Pro Arg
11490 11495 11500
Thr Thr Pro Lys Phe Ser His Ser Lys Ser Asp Thr Thr Leu Pro Val
11505 11510 11515 11520
Ala Ile Thr Ser Pro Gly Pro Glu Ala Ser Ser Ala Val Ser Thr Thr
11525 11530 11535
Thr Ile Ser Pro Asp Met Ser Asp Leu Val Thr Ser Leu Val Pro Ser
11540 11545 11550
Ser Gly Thr Asp Thr Ser Thr Thr Phe Pro Thr Leu Ser Glu Thr Pro
11555 11560 11565
Tyr Glu Pro Glu Thr Thr Ala Thr Trp Leu Thr His Pro Ala Glu Thr
11570 11575 11580
Ser Thr Thr Val Ser Gly Thr Ile Pro Asn Phe Ser His Arg Gly Ser
11585 11590 11595 11600
Asp Thr Ala Pro Ser Met Val Thr Ser Pro Gly Val Asp Thr Arg Ser
11605 11610 11615
Gly Val Pro Thr Thr Thr Ile Pro Pro Ser Ile Pro Gly Val Val Thr
11620 11625 11630
Ser Gln Val Thr Ser Ser Ala Thr Asp Thr Ser Thr Ala Ile Pro Thr
11635 11640 11645
Leu Thr Pro Ser Pro Gly Glu Pro Glu Thr Thr Ala Ser Ser Ala Thr
11650 11655 11660
His Pro Gly Thr Gln Thr Gly Phe Thr Val Pro Ile Arg Thr Val Pro
11665 11670 11675 11680
Ser Ser Glu Pro Asp Thr Met Ala Ser Trp Val Thr His Pro Pro Gln
11685 11690 11695
Thr Ser Thr Pro Val Ser Arg Thr Thr Ser Ser Phe Ser His Ser Ser
11700 11705 11710
Pro Asp Ala Thr Pro Val Met Ala Thr Ser Pro Arg Thr Glu Ala Ser
11715 11720 11725
Ser Ala Val Leu Thr Thr Ile Ser Pro Gly Ala Pro Glu Met Val Thr
11730 11735 11740
Ser Gln Ile Thr Ser Ser Gly Ala Ala Thr Ser Thr Thr Val Pro Thr
11745 11750 11755 11760
Leu Thr His Ser Pro Gly Met Pro Glu Thr Thr Ala Leu Leu Ser Thr
11765 11770 11775
His Pro Arg Thr Glu Thr Ser Lys Thr Phe Pro Ala Ser Thr Val Phe
11780 11785 11790
Pro Gln Val Ser Glu Thr Thr Ala Ser Leu Thr Ile Arg Pro Gly Ala
11795 11800 11805
Glu Thr Ser Thr Ala Leu Pro Thr Gln Thr Thr Ser Ser Leu Phe Thr
11810 11815 11820
Leu Leu Val Thr Gly Thr Ser Arg Val Asp Leu Ser Pro Thr Ala Ser
11825 11830 11835 11840
Pro Gly Val Ser Ala Lys Thr Ala Pro Leu Ser Thr His Pro Gly Thr
11845 11850 11855
Glu Thr Ser Thr Met Ile Pro Thr Ser Thr Leu Ser Leu Gly Leu Leu
11860 11865 11870
Glu Thr Thr Gly Leu Leu Ala Thr Ser Ser Ser Ala Glu Thr Ser Thr
11875 11880 11885
Ser Thr Leu Thr Leu Thr Val Ser Pro Ala Val Ser Gly Leu Ser Ser
11890 11895 11900
Ala Ser Ile Thr Thr Asp Lys Pro Gln Thr Val Thr Ser Trp Asn Thr
11905 11910 11915 11920
Glu Thr Ser Pro Ser Val Thr Ser Val Gly Pro Pro Glu Phe Ser Arg
11925 11930 11935
Thr Val Thr Gly Thr Thr Met Thr Leu Ile Pro Ser Glu Met Pro Thr
11940 11945 11950
Pro Pro Lys Thr Ser His Gly Glu Gly Val Ser Pro Thr Thr Ile Leu
11955 11960 11965
Arg Thr Thr Met Val Glu Ala Thr Asn Leu Ala Thr Thr Gly Ser Ser
11970 11975 11980
Pro Thr Val Ala Lys Thr Thr Thr Thr Phe Asn Thr Leu Ala Gly Ser
11985 11990 11995 12000
Leu Phe Thr Pro Leu Thr Thr Pro Gly Met Ser Thr Leu Ala Ser Glu
12005 12010 12015
Ser Val Thr Ser Arg Thr Ser Tyr Asn His Arg Ser Trp Ile Ser Thr
12020 12025 12030
Thr Ser Ser Tyr Asn Arg Arg Tyr Trp Thr Pro Ala Thr Ser Thr Pro
12035 12040 12045
Val Thr Ser Thr Phe Ser Pro Gly Ile Ser Thr Ser Ser Ile Pro Ser
12050 12055 12060
Ser Thr Ala Ala Thr Val Pro Phe Met Val Pro Phe Thr Leu Asn Phe
12065 12070 12075 12080
Thr Ile Thr Asn Leu Gln Tyr Glu Glu Asp Met Arg His Pro Gly Ser
12085 12090 12095
Arg Lys Phe Asn Ala Thr Glu Arg Glu Leu Gln Gly Leu Leu Lys Pro
12100 12105 12110
Leu Phe Arg Asn Ser Ser Leu Glu Tyr Leu Tyr Ser Gly Cys Arg Leu
12115 12120 12125
Ala Ser Leu Arg Pro Glu Lys Asp Ser Ser Ala Thr Ala Val Asp Ala
12130 12135 12140
Ile Cys Thr His Arg Pro Asp Pro Glu Asp Leu Gly Leu Asp Arg Glu
12145 12150 12155 12160
Arg Leu Tyr Trp Glu Leu Ser Asn Leu Thr Asn Gly Ile Gln Glu Leu
12165 12170 12175
Gly Pro Tyr Thr Leu Asp Arg Asn Ser Leu Tyr Val Asn Gly Phe Thr
12180 12185 12190
His Arg Ser Ser Met Pro Thr Thr Ser Thr Pro Gly Thr Ser Thr Val
12195 12200 12205
Asp Val Gly Thr Ser Gly Thr Pro Ser Ser Ser Pro Ser Pro Thr Thr
12210 12215 12220
Ala Gly Pro Leu Leu Met Pro Phe Thr Leu Asn Phe Thr Ile Thr Asn
12225 12230 12235 12240
Leu Gln Tyr Glu Glu Asp Met Arg Arg Thr Gly Ser Arg Lys Phe Asn
12245 12250 12255
Thr Met Glu Ser Val Leu Gln Gly Leu Leu Lys Pro Leu Phe Lys Asn
12260 12265 12270
Thr Ser Val Gly Pro Leu Tyr Ser Gly Cys Arg Leu Thr Leu Leu Arg
12275 12280 12285
Pro Glu Lys Asp Gly Ala Ala Thr Gly Val Asp Ala Ile Cys Thr His
12290 12295 12300
Arg Leu Asp Pro Lys Ser Pro Gly Leu Asn Arg Glu Gln Leu Tyr Trp
12305 12310 12315 12320
Glu Leu Ser Lys Leu Thr Asn Asp Ile Glu Glu Leu Gly Pro Tyr Thr
12325 12330 12335
Leu Asp Arg Asn Ser Leu Tyr Val Asn Gly Phe Thr His Gln Ser Ser
12340 12345 12350
Val Ser Thr Thr Ser Thr Pro Gly Thr Ser Thr Val Asp Leu Arg Thr
12355 12360 12365
Ser Gly Thr Pro Ser Ser Leu Ser Ser Pro Thr Ile Met Ala Ala Gly
12370 12375 12380
Pro Leu Leu Val Pro Phe Thr Leu Asn Phe Thr Ile Thr Asn Leu Gln
12385 12390 12395 12400
Tyr Gly Glu Asp Met Gly His Pro Gly Ser Arg Lys Phe Asn Thr Thr
12405 12410 12415
Glu Arg Val Leu Gln Gly Leu Leu Gly Pro Ile Phe Lys Asn Thr Ser
12420 12425 12430
Val Gly Pro Leu Tyr Ser Gly Cys Arg Leu Thr Ser Leu Arg Ser Glu
12435 12440 12445
Lys Asp Gly Ala Ala Thr Gly Val Asp Ala Ile Cys Ile His His Leu
12450 12455 12460
Asp Pro Lys Ser Pro Gly Leu Asn Arg Glu Arg Leu Tyr Trp Glu Leu
12465 12470 12475 12480
Ser Gln Leu Thr Asn Gly Ile Lys Glu Leu Gly Pro Tyr Thr Leu Asp
12485 12490 12495
Arg Asn Ser Leu Tyr Val Asn Gly Phe Thr His Arg Thr Ser Val Pro
12500 12505 12510
Thr Ser Ser Thr Pro Gly Thr Ser Thr Val Asp Leu Gly Thr Ser Gly
12515 12520 12525
Thr Pro Phe Ser Leu Pro Ser Pro Ala Thr Ala Gly Pro Leu Leu Val
12530 12535 12540
Leu Phe Thr Leu Asn Phe Thr Ile Thr Asn Leu Lys Tyr Glu Glu Asp
12545 12550 12555 12560
Met His Arg Pro Gly Ser Arg Lys Phe Asn Thr Thr Glu Arg Val Leu
12565 12570 12575
Gln Thr Leu Leu Gly Pro Met Phe Lys Asn Thr Ser Val Gly Leu Leu
12580 12585 12590
Tyr Ser Gly Cys Arg Leu Thr Leu Leu Arg Ser Glu Lys Asp Gly Ala
12595 12600 12605
Ala Thr Gly Val Asp Ala Ile Cys Thr His Arg Leu Asp Pro Lys Ser
12610 12615 12620
Pro Gly Val Asp Arg Glu Gln Leu Tyr Trp Glu Leu Ser Gln Leu Thr
12625 12630 12635 12640
Asn Gly Ile Lys Glu Leu Gly Pro Tyr Thr Leu Asp Arg Asn Ser Leu
12645 12650 12655
Tyr Val Asn Gly Phe Thr His Trp Ile Pro Val Pro Thr Ser Ser Thr
12660 12665 12670
Pro Gly Thr Ser Thr Val Asp Leu Gly Ser Gly Thr Pro Ser Ser Leu
12675 12680 12685
Pro Ser Pro Thr Thr Ala Gly Pro Leu Leu Val Pro Phe Thr Leu Asn
12690 12695 12700
Phe Thr Ile Thr Asn Leu Lys Tyr Glu Glu Asp Met His Cys Pro Gly
12705 12710 12715 12720
Ser Arg Lys Phe Asn Thr Thr Glu Arg Val Leu Gln Ser Leu Leu Gly
12725 12730 12735
Pro Met Phe Lys Asn Thr Ser Val Gly Pro Leu Tyr Ser Gly Cys Arg
12740 12745 12750
Leu Thr Leu Leu Arg Ser Glu Lys Asp Gly Ala Ala Thr Gly Val Asp
12755 12760 12765
Ala Ile Cys Thr His Arg Leu Asp Pro Lys Ser Pro Gly Val Asp Arg
12770 12775 12780
Glu Gln Leu Tyr Trp Glu Leu Ser Gln Leu Thr Asn Gly Ile Lys Glu
12785 12790 12795 12800
Leu Gly Pro Tyr Thr Leu Asp Arg Asn Ser Leu Tyr Val Asn Gly Phe
12805 12810 12815
Thr His Gln Thr Ser Ala Pro Asn Thr Ser Thr Pro Gly Thr Ser Thr
12820 12825 12830
Val Asp Leu Gly Thr Ser Gly Thr Pro Ser Ser Leu Pro Ser Pro Thr
12835 12840 12845
Ser Ala Gly Pro Leu Leu Val Pro Phe Thr Leu Asn Phe Thr Ile Thr
12850 12855 12860
Asn Leu Gln Tyr Glu Glu Asp Met His His Pro Gly Ser Arg Lys Phe
12865 12870 12875 12880
Asn Thr Thr Glu Arg Val Leu Gln Gly Leu Leu Gly Pro Met Phe Lys
12885 12890 12895
Asn Thr Ser Val Gly Leu Leu Tyr Ser Gly Cys Arg Leu Thr Leu Leu
12900 12905 12910
Arg Pro Glu Lys Asn Gly Ala Ala Thr Gly Met Asp Ala Ile Cys Ser
12915 12920 12925
His Arg Leu Asp Pro Lys Ser Pro Gly Leu Asn Arg Glu Gln Leu Tyr
12930 12935 12940
Trp Glu Leu Ser Gln Leu Thr His Gly Ile Lys Glu Leu Gly Pro Tyr
12945 12950 12955 12960
Thr Leu Asp Arg Asn Ser Leu Tyr Val Asn Gly Phe Thr His Arg Ser
12965 12970 12975
Ser Val Ala Pro Thr Ser Thr Pro Gly Thr Ser Thr Val Asp Leu Gly
12980 12985 12990
Thr Ser Gly Thr Pro Ser Ser Leu Pro Ser Pro Thr Thr Ala Val Pro
12995 13000 13005
Leu Leu Val Pro Phe Thr Leu Asn Phe Thr Ile Thr Asn Leu Gln Tyr
13010 13015 13020
Gly Glu Asp Met Arg His Pro Gly Ser Arg Lys Phe Asn Thr Thr Glu
13025 13030 13035 13040
Arg Val Leu Gln Gly Leu Leu Gly Pro Leu Phe Lys Asn Ser Ser Val
13045 13050 13055
Gly Pro Leu Tyr Ser Gly Cys Arg Leu Ile Ser Leu Arg Ser Glu Lys
13060 13065 13070
Asp Gly Ala Ala Thr Gly Val Asp Ala Ile Cys Thr His His Leu Asn
13075 13080 13085
Pro Gln Ser Pro Gly Leu Asp Arg Glu Gln Leu Tyr Trp Gln Leu Ser
13090 13095 13100
Gln Met Thr Asn Gly Ile Lys Glu Leu Gly Pro Tyr Thr Leu Asp Arg
13105 13110 13115 13120
Asn Ser Leu Tyr Val Asn Gly Phe Thr His Arg Ser Ser Gly Leu Thr
13125 13130 13135
Thr Ser Thr Pro Trp Thr Ser Thr Val Asp Leu Gly Thr Ser Gly Thr
13140 13145 13150
Pro Ser Pro Val Pro Ser Pro Thr Thr Thr Gly Pro Leu Leu Val Pro
13155 13160 13165
Phe Thr Leu Asn Phe Thr Ile Thr Asn Leu Gln Tyr Glu Glu Asn Met
13170 13175 13180
Gly His Pro Gly Ser Arg Lys Phe Asn Ile Thr Glu Ser Val Leu Gln
13185 13190 13195 13200
Gly Leu Leu Lys Pro Leu Phe Lys Ser Thr Ser Val Gly Pro Leu Tyr
13205 13210 13215
Ser Gly Cys Arg Leu Thr Leu Leu Arg Pro Glu Lys Asp Gly Val Ala
13220 13225 13230
Thr Arg Val Asp Ala Ile Cys Thr His Arg Pro Asp Pro Lys Ile Pro
13235 13240 13245
Gly Leu Asp Arg Gln Gln Leu Tyr Trp Glu Leu Ser Gln Leu Thr His
13250 13255 13260
Ser Ile Thr Glu Leu Gly Pro Tyr Thr Leu Asp Arg Asp Ser Leu Tyr
13265 13270 13275 13280
Val Asn Gly Phe Thr Gln Arg Ser Ser Val Pro Thr Thr Ser Thr Pro
13285 13290 13295
Gly Thr Phe Thr Val Gln Pro Glu Thr Ser Glu Thr Pro Ser Ser Leu
13300 13305 13310
Pro Gly Pro Thr Ala Thr Gly Pro Val Leu Leu Pro Phe Thr Leu Asn
13315 13320 13325
Phe Thr Ile Thr Asn Leu Gln Tyr Glu Glu Asp Met Arg Arg Pro Gly
13330 13335 13340
Ser Arg Lys Phe Asn Thr Thr Glu Arg Val Leu Gln Gly Leu Leu Met
13345 13350 13355 13360
Pro Leu Phe Lys Asn Thr Ser Val Ser Ser Leu Tyr Ser Gly Cys Arg
13365 13370 13375
Leu Thr Leu Leu Arg Pro Glu Lys Asp Gly Ala Ala Thr Arg Val Asp
13380 13385 13390
Ala Val Cys Thr His Arg Pro Asp Pro Lys Ser Pro Gly Leu Asp Arg
13395 13400 13405
Glu Arg Leu Tyr Trp Lys Leu Ser Gln Leu Thr His Gly Ile Thr Glu
13410 13415 13420
Leu Gly Pro Tyr Thr Leu Asp Arg His Ser Leu Tyr Val Asn Gly Phe
13425 13430 13435 13440
Thr His Gln Ser Ser Met Thr Thr Thr Arg Thr Pro Asp Thr Ser Thr
13445 13450 13455
Met His Leu Ala Thr Ser Arg Thr Pro Ala Ser Leu Ser Gly Pro Met
13460 13465 13470
Thr Ala Ser Pro Leu Leu Val Leu Phe Thr Ile Asn Phe Thr Ile Thr
13475 13480 13485
Asn Leu Arg Tyr Glu Glu Asn Met His His Pro Gly Ser Arg Lys Phe
13490 13495 13500
Asn Thr Thr Glu Arg Val Leu Gln Gly Leu Leu Arg Pro Val Phe Lys
13505 13510 13515 13520
Asn Thr Ser Val Gly Pro Leu Tyr Ser Gly Cys Arg Leu Thr Leu Leu
13525 13530 13535
Arg Pro Lys Lys Asp Gly Ala Ala Thr Lys Val Asp Ala Ile Cys Thr
13540 13545 13550
Tyr Arg Pro Asp Pro Lys Ser Pro Gly Leu Asp Arg Glu Gln Leu Tyr
13555 13560 13565
Trp Glu Leu Ser Gln Leu Thr His Ser Ile Thr Glu Leu Gly Pro Tyr
13570 13575 13580
Thr Leu Asp Arg Asp Ser Leu Tyr Val Asn Gly Phe Thr Gln Arg Ser
13585 13590 13595 13600
Ser Val Pro Thr Thr Ser Ile Pro Gly Thr Pro Thr Val Asp Leu Gly
13605 13610 13615
Thr Ser Gly Thr Pro Val Ser Lys Pro Gly Pro Ser Ala Ala Ser Pro
13620 13625 13630
Leu Leu Val Leu Phe Thr Leu Asn Phe Thr Ile Thr Asn Leu Arg Tyr
13635 13640 13645
Glu Glu Asn Met Gln His Pro Gly Ser Arg Lys Phe Asn Thr Thr Glu
13650 13655 13660
Arg Val Leu Gln Gly Leu Leu Arg Ser Leu Phe Lys Ser Thr Ser Val
13665 13670 13675 13680
Gly Pro Leu Tyr Ser Gly Cys Arg Leu Thr Leu Leu Arg Pro Glu Lys
13685 13690 13695
Asp Gly Thr Ala Thr Gly Val Asp Ala Ile Cys Thr His His Pro Asp
13700 13705 13710
Pro Lys Ser Pro Arg Leu Asp Arg Glu Gln Leu Tyr Trp Glu Leu Ser
13715 13720 13725
Gln Leu Thr His Asn Ile Thr Glu Leu Gly Pro Tyr Ala Leu Asp Asn
13730 13735 13740
Asp Ser Leu Phe Val Asn Gly Phe Thr His Arg Ser Ser Val Ser Thr
13745 13750 13755 13760
Thr Ser Thr Pro Gly Thr Pro Thr Val Tyr Leu Gly Ala Ser Lys Thr
13765 13770 13775
Pro Ala Ser Ile Phe Gly Pro Ser Ala Ala Ser His Leu Leu Ile Leu
13780 13785 13790
Phe Thr Leu Asn Phe Thr Ile Thr Asn Leu Arg Tyr Glu Glu Asn Met
13795 13800 13805
Trp Pro Gly Ser Arg Lys Phe Asn Thr Thr Glu Arg Val Leu Gln Gly
13810 13815 13820
Leu Leu Arg Pro Leu Phe Lys Asn Thr Ser Val Gly Pro Leu Tyr Ser
13825 13830 13835 13840
Gly Cys Arg Leu Thr Leu Leu Arg Pro Glu Lys Asp Gly Glu Ala Thr
13845 13850 13855
Gly Val Asp Ala Ile Cys Thr His Arg Pro Asp Pro Thr Gly Pro Gly
13860 13865 13870
Leu Asp Arg Glu Gln Leu Tyr Leu Glu Leu Ser Gln Leu Thr His Ser
13875 13880 13885
Ile Thr Glu Leu Gly Pro Tyr Thr Leu Asp Arg Asp Ser Leu Tyr Val
13890 13895 13900
Asn Gly Phe Thr His Arg Ser Ser Val Pro Thr Thr Ser Thr Gly Val
13905 13910 13915 13920
Val Ser Glu Glu Pro Phe Thr Leu Asn Phe Thr Ile Asn Asn Leu Arg
13925 13930 13935
Tyr Met Ala Asp Met Gly Gln Pro Gly Ser Leu Lys Phe Asn Ile Thr
13940 13945 13950
Asp Asn Val Met Gln His Leu Leu Ser Pro Leu Phe Gln Arg Ser Ser
13955 13960 13965
Leu Gly Ala Arg Tyr Thr Gly Cys Arg Val Ile Ala Leu Arg Ser Val
13970 13975 13980
Lys Asn Gly Ala Glu Thr Arg Val Asp Leu Leu Cys Thr Tyr Leu Gln
13985 13990 13995 14000
Pro Leu Ser Gly Pro Gly Leu Pro Ile Lys Gln Val Phe His Glu Leu
14005 14010 14015
Ser Gln Gln Thr His Gly Ile Thr Arg Leu Gly Pro Tyr Ser Leu Asp
14020 14025 14030
Lys Asp Ser Leu Tyr Leu Asn Gly Tyr Asn Glu Pro Gly Pro Asp Glu
14035 14040 14045
Pro Pro Thr Thr Pro Lys Pro Ala Thr Thr Phe Leu Pro Pro Leu Ser
14050 14055 14060
Glu Ala Thr Thr Ala Met Gly Tyr His Leu Lys Thr Leu Thr Leu Asn
14065 14070 14075 14080
Phe Thr Ile Ser Asn Leu Gln Tyr Ser Pro Asp Met Gly Lys Gly Ser
14085 14090 14095
Ala Thr Phe Asn Ser Thr Glu Gly Val Leu Gln His Leu Leu Arg Pro
14100 14105 14110
Leu Phe Gln Lys Ser Ser Met Gly Pro Phe Tyr Leu Gly Cys Gln Leu
14115 14120 14125
Ile Ser Leu Arg Pro Glu Lys Asp Gly Ala Ala Thr Gly Val Asp Thr
14130 14135 14140
Thr Cys Thr Tyr His Pro Asp Pro Val Gly Pro Gly Leu Asp Ile Gln
14145 14150 14155 14160
Gln Leu Tyr Trp Glu Leu Ser Gln Leu Thr His Gly Val Thr Gln Leu
14165 14170 14175
Gly Phe Tyr Val Leu Asp Arg Asp Ser Leu Phe Ile Asn Gly Tyr Ala
14180 14185 14190
Pro Gln Asn Leu Ser Ile Arg Gly Glu Tyr Gln Ile Asn Phe His Ile
14195 14200 14205
Val Asn Trp Asn Leu Ser Asn Pro Asp Pro Thr Ser Ser Glu Tyr Ile
14210 14215 14220
Thr Leu Leu Arg Asp Ile Gln Asp Lys Val Thr Thr Leu Tyr Lys Gly
14225 14230 14235 14240
Ser Gln Leu His Asp Thr Phe Arg Phe Cys Leu Val Thr Asn Leu Thr
14245 14250 14255
Met Asp Ser Val Leu Val Thr Val Lys Ala Leu Phe Ser Ser Asn Leu
14260 14265 14270
Asp Pro Ser Leu Val Glu Gln Val Phe Leu Asp Lys Thr Leu Asn Ala
14275 14280 14285
Ser Phe His Trp Leu Gly Ser Thr Tyr Gln Leu Val Asp Ile His Val
14290 14295 14300
Thr Glu Met Glu Ser Ser Val Tyr Gln Pro Thr Ser Ser Ser Ser Thr
14305 14310 14315 14320
Gln His Phe Tyr Leu Asn Phe Thr Ile Thr Asn Leu Pro Tyr Ser Gln
14325 14330 14335
Asp Lys Ala Gln Pro Gly Thr Thr Asn Tyr Gln Arg Asn Lys Arg Asn
14340 14345 14350
Ile Glu Asp Ala Leu Asn Gln Leu Phe Arg Asn Ser Ser Ile Lys Ser
14355 14360 14365
Tyr Phe Ser Asp Cys Gln Val Ser Thr Phe Arg Ser Val Pro Asn Arg
14370 14375 14380
His His Thr Gly Val Asp Ser Leu Cys Asn Phe Ser Pro Leu Ala Arg
14385 14390 14395 14400
Arg Val Asp Arg Val Ala Ile Tyr Glu Glu Phe Leu Arg Met Thr Arg
14405 14410 14415
Asn Gly Thr Gln Leu Gln Asn Phe Thr Leu Asp Arg Ser Ser Val Leu
14420 14425 14430
Val Asp Gly Tyr Ser Pro Asn Arg Asn Glu Pro Leu Thr Gly Asn Ser
14435 14440 14445
Asp Leu Pro Phe Trp Ala Val Ile Leu Ile Gly Leu Ala Gly Leu Leu
14450 14455 14460
Gly Val Ile Thr Cys Leu Ile Cys Gly Val Leu Val Thr Thr Arg Arg
14465 14470 14475 14480
Arg Lys Lys Glu Gly Glu Tyr Asn Val Gln Gln Gln Cys Pro Gly Tyr
14485 14490 14495
Tyr Gln Ser His Leu Asp Leu Glu Asp Leu Gln
14500 14505
<210> 7
<211> 267
<212> PRT
<213> 智人（Homo sapiens）
<400> 7
Met Met Ser Ser Lys Pro Thr Ser His Ala Glu Val Asn Glu Thr Ile
1 5 10 15
Pro Asn Pro Tyr Pro Pro Ser Ser Phe Met Ala Pro Gly Phe Gln Gln
20 25 30
Pro Leu Gly Ser Ile Asn Leu Glu Asn Gln Ala Gln Gly Ala Gln Arg
35 40 45
Ala Gln Pro Tyr Gly Ile Thr Ser Pro Gly Ile Phe Ala Ser Ser Gln
50 55 60
Pro Gly Gln Gly Asn Ile Gln Met Ile Asn Pro Ser Val Gly Thr Ala
65 70 75 80
Val Met Asn Phe Lys Glu Glu Ala Lys Ala Leu Gly Val Ile Gln Ile
85 90 95
Met Val Gly Leu Met His Ile Gly Phe Gly Ile Val Leu Cys Leu Ile
100 105 110
Ser Phe Ser Phe Arg Glu Val Leu Gly Phe Ala Ser Thr Ala Val Ile
115 120 125
Gly Gly Tyr Pro Phe Trp Gly Gly Leu Ser Phe Ile Ile Ser Gly Ser
130 135 140
Leu Ser Val Ser Ala Ser Lys Glu Leu Ser Arg Cys Leu Val Lys Gly
145 150 155 160
Ser Leu Gly Met Asn Ile Val Ser Ser Ile Leu Ala Phe Ile Gly Val
165 170 175
Ile Leu Leu Leu Val Asp Met Cys Ile Asn Gly Val Ala Gly Gln Asp
180 185 190
Tyr Trp Ala Val Leu Ser Gly Lys Gly Ile Ser Ala Thr Leu Met Ile
195 200 205
Phe Ser Leu Leu Glu Phe Phe Val Ala Cys Ala Thr Ala His Phe Ala
210 215 220
Asn Gln Ala Asn Thr Thr Thr Asn Met Ser Val Leu Val Ile Pro Asn
225 230 235 240
Met Tyr Glu Ser Asn Pro Val Thr Pro Ala Ser Ser Ser Ala Pro Pro
245 250 255
Arg Cys Asn Asn Tyr Ser Ala Asn Ala Pro Lys
260 265
<210> 8
<211> 535
<212> PRT
<213> 智人（Homo sapiens）
<400> 8
Met Leu Gly Pro Cys Met Leu Leu Leu Leu Leu Leu Leu Gly Leu Arg
1 5 10 15
Leu Gln Leu Ser Leu Gly Ile Ile Pro Val Glu Glu Glu Asn Pro Asp
20 25 30
Phe Trp Asn Arg Glu Ala Ala Glu Ala Leu Gly Ala Ala Lys Lys Leu
35 40 45
Gln Pro Ala Gln Thr Ala Ala Lys Asn Leu Ile Ile Phe Leu Gly Asp
50 55 60
Gly Met Gly Val Ser Thr Val Thr Ala Ala Arg Ile Leu Lys Gly Gln
65 70 75 80
Lys Lys Asp Lys Leu Gly Pro Glu Ile Pro Leu Ala Met Asp Arg Phe
85 90 95
Pro Tyr Val Ala Leu Ser Lys Thr Tyr Asn Val Asp Lys His Val Pro
100 105 110
Asp Ser Gly Ala Thr Ala Thr Ala Tyr Leu Cys Gly Val Lys Gly Asn
115 120 125
Phe Gln Thr Ile Gly Leu Ser Ala Ala Ala Arg Phe Asn Gln Cys Asn
130 135 140
Thr Thr Arg Gly Asn Glu Val Ile Ser Val Met Asn Arg Ala Lys Lys
145 150 155 160
Ala Gly Lys Ser Val Gly Val Val Thr Thr Thr Arg Val Gln His Ala
165 170 175
Ser Pro Ala Gly Thr Tyr Ala His Thr Val Asn Arg Asn Trp Tyr Ser
180 185 190
Asp Ala Asp Val Pro Ala Ser Ala Arg Gln Glu Gly Cys Gln Asp Ile
195 200 205
Ala Thr Gln Leu Ile Ser Asn Met Asp Ile Asp Val Ile Leu Gly Gly
210 215 220
Gly Arg Lys Tyr Met Phe Arg Met Gly Thr Pro Asp Pro Glu Tyr Pro
225 230 235 240
Asp Asp Tyr Ser Gln Gly Gly Thr Arg Leu Asp Gly Lys Asn Leu Val
245 250 255
Gln Glu Trp Leu Ala Lys Arg Gln Gly Ala Arg Tyr Val Trp Asn Arg
260 265 270
Thr Glu Leu Met Gln Ala Ser Leu Asp Pro Ser Val Thr His Leu Met
275 280 285
Gly Leu Phe Glu Pro Gly Asp Met Lys Tyr Glu Ile His Arg Asp Ser
290 295 300
Thr Leu Asp Pro Ser Leu Met Glu Met Thr Glu Ala Ala Leu Arg Leu
305 310 315 320
Leu Ser Arg Asn Pro Arg Gly Phe Phe Leu Phe Val Glu Gly Gly Arg
325 330 335
Ile Asp His Gly His His Glu Ser Arg Ala Tyr Arg Ala Leu Thr Glu
340 345 350
Thr Ile Met Phe Asp Asp Ala Ile Glu Arg Ala Gly Gln Leu Thr Ser
355 360 365
Glu Glu Asp Thr Leu Ser Leu Val Thr Ala Asp His Ser His Val Phe
370 375 380
Ser Phe Gly Gly Tyr Pro Leu Arg Gly Ser Ser Ile Phe Gly Leu Ala
385 390 395 400
Pro Gly Lys Ala Arg Asp Arg Lys Ala Tyr Thr Val Leu Leu Tyr Gly
405 410 415
Asn Gly Pro Gly Tyr Val Leu Lys Asp Gly Ala Arg Pro Asp Val Thr
420 425 430
Glu Ser Glu Ser Gly Ser Pro Glu Tyr Arg Gln Gln Ser Ala Val Pro
435 440 445
Leu Asp Glu Glu Thr His Ala Gly Glu Asp Val Ala Val Phe Ala Arg
450 455 460
Gly Pro Gln Ala His Leu Val His Gly Val Gln Glu Gln Thr Phe Ile
465 470 475 480
Ala His Val Met Ala Phe Ala Ala Cys Leu Glu Pro Tyr Thr Ala Cys
485 490 495
Asp Leu Ala Pro Pro Ala Gly Thr Thr Asp Ala Ala His Pro Gly Arg
500 505 510
Ser Val Val Pro Ala Leu Leu Pro Leu Leu Ala Gly Thr Leu Leu Leu
515 520 525
Leu Glu Thr Ala Thr Ala Pro
530 535
<210> 9
<211> 520
<212> PRT
<213> 智人（Homo sapiens）
<400> 9
Met Glu Phe His Asn Gly Gly His Val Ser Gly Ile Gly Gly Phe Leu
1 5 10 15
Val Ser Leu Thr Ser Arg Met Lys Pro His Thr Leu Ala Val Thr Pro
20 25 30
Ala Leu Ile Phe Ala Ile Thr Val Ala Thr Ile Gly Ser Phe Gln Phe
35 40 45
Gly Tyr Asn Thr Gly Val Ile Asn Ala Pro Glu Thr Ile Ile Lys Glu
50 55 60
Phe Ile Asn Lys Thr Leu Thr Asp Lys Ala Asn Ala Pro Pro Ser Glu
65 70 75 80
Val Leu Leu Thr Asn Leu Trp Ser Leu Ser Val Ala Ile Phe Ser Val
85 90 95
Gly Gly Met Ile Gly Ser Phe Ser Val Gly Leu Phe Val Asn Arg Phe
100 105 110
Gly Arg Arg Asn Ser Met Leu Ile Val Asn Leu Leu Ala Ala Thr Gly
115 120 125
Gly Cys Leu Met Gly Leu Cys Lys Ile Ala Glu Ser Val Glu Met Leu
130 135 140
Ile Leu Gly Arg Leu Val Ile Gly Leu Phe Cys Gly Leu Cys Thr Gly
145 150 155 160
Phe Val Pro Met Tyr Ile Gly Glu Ile Ser Pro Thr Ala Leu Arg Gly
165 170 175
Ala Phe Gly Thr Leu Asn Gln Leu Gly Ile Val Ile Gly Ile Leu Val
180 185 190
Ala Gln Ile Phe Gly Leu Glu Leu Ile Leu Gly Ser Glu Glu Leu Trp
195 200 205
Pro Val Leu Leu Gly Phe Thr Ile Leu Pro Ala Ile Leu Gln Ser Ala
210 215 220
Ala Leu Pro Cys Cys Pro Glu Ser Pro Arg Phe Leu Leu Ile Asn Arg
225 230 235 240
Lys Lys Glu Glu Asn Ala Thr Arg Ile Leu Gln Arg Leu Trp Gly Thr
245 250 255
Gln Asp Val Ser Gln Asp Ile Gln Glu Met Lys Asp Glu Ser Ala Arg
260 265 270
Met Ser Gln Glu Lys Gln Val Thr Val Leu Glu Leu Phe Arg Val Ser
275 280 285
Ser Tyr Arg Gln Pro Ile Ile Ile Ser Ile Val Leu Gln Leu Ser Gln
290 295 300
Gln Leu Ser Gly Ile Asn Ala Val Phe Tyr Tyr Ser Thr Gly Ile Phe
305 310 315 320
Lys Asp Ala Gly Val Gln Gln Pro Ile Tyr Ala Thr Ile Ser Ala Gly
325 330 335
Val Val Asn Thr Ile Phe Thr Leu Leu Ser Leu Phe Leu Val Glu Arg
340 345 350
Ala Gly Arg Arg Thr Leu His Met Ile Gly Leu Gly Gly Met Ala Phe
355 360 365
Cys Ser Thr Leu Met Thr Val Ser Leu Leu Leu Lys Asn His Tyr Asn
370 375 380
Gly Met Ser Phe Val Cys Ile Gly Ala Ile Leu Val Phe Val Ala Cys
385 390 395 400
Phe Glu Ile Gly Pro Gly Pro Ile Pro Trp Phe Ile Val Ala Glu Leu
405 410 415
Phe Ser Gln Gly Pro Arg Pro Ala Ala Met Ala Val Ala Gly Cys Ser
420 425 430
Asn Trp Thr Ser Asn Phe Leu Val Gly Leu Leu Phe Pro Ser Ala Ala
435 440 445
Tyr Tyr Leu Gly Ala Tyr Val Phe Ile Ile Phe Thr Gly Phe Leu Ile
450 455 460
Thr Phe Leu Ala Phe Thr Phe Phe Lys Val Pro Glu Thr Arg Gly Arg
465 470 475 480
Thr Phe Glu Asp Ile Thr Arg Ala Phe Glu Gly Gln Ala His Gly Ala
485 490 495
Asp Arg Ser Gly Lys Asp Gly Val Met Gly Met Asn Ser Ile Glu Pro
500 505 510
Ala Lys Glu Thr Thr Thr Asn Val
515 520
<210> 10
<211> 221
<212> PRT
<213> 智人（Homo sapiens）
<400> 10
Met Leu Thr Leu Glu Asp Lys Asp Met Lys Gly Phe Ser Trp Ala Ile
1 5 10 15
Val Pro Ala Leu Thr Ser Leu Gly Tyr Leu Ile Ile Leu Val Val Ser
20 25 30
Ile Phe Pro Phe Trp Val Arg Leu Thr Asn Glu Glu Ser His Glu Val
35 40 45
Phe Phe Ser Gly Leu Phe Glu Asn Cys Phe Asn Ala Lys Cys Trp Lys
50 55 60
Pro Arg Pro Leu Ser Ile Tyr Ile Ile Leu Gly Arg Val Phe Leu Leu
65 70 75 80
Ser Ala Val Phe Leu Ala Phe Val Thr Thr Phe Ile Met Met Pro Phe
85 90 95
Ala Ser Glu Phe Phe Pro Arg Thr Trp Lys Gln Asn Phe Val Leu Ala
100 105 110
Cys Ile Ser Phe Phe Thr Gly Ala Cys Ala Phe Leu Ala Leu Val Leu
115 120 125
His Ala Leu Glu Ile Lys Ala Leu Arg Met Lys Leu Gly Pro Leu Gln
130 135 140
Phe Ser Val Leu Trp Pro Tyr Tyr Val Leu Gly Phe Gly Ile Phe Leu
145 150 155 160
Phe Ile Val Ala Gly Thr Ile Cys Leu Ile Gln Glu Met Val Cys Pro
165 170 175
Cys Trp His Leu Leu Ser Thr Ser Gln Ser Met Glu Glu Asp His Gly
180 185 190
Ser Leu Tyr Leu Asp Asn Leu Glu Ser Leu Gly Gly Glu Pro Ser Ser
195 200 205
Val Gln Lys Glu Thr Gln Val Thr Ala Glu Thr Val Ile
210 215 220
<210> 11
<211> 538
<212> PRT
<213> 智人（Homo sapiens）
<400> 11
Met Gly Leu Leu Leu Leu Val Leu Ile Leu Thr Pro Ser Leu Ala Ala
1 5 10 15
Tyr Arg His Pro Asp Phe Pro Leu Leu Glu Lys Ala Gln Gln Leu Leu
20 25 30
Gln Ser Thr Gly Ser Pro Tyr Ser Thr Asn Cys Trp Leu Cys Thr Ser
35 40 45
Ser Ser Thr Glu Thr Pro Gly Thr Ala Tyr Pro Ala Ser Pro Arg Glu
50 55 60
Trp Thr Ser Ile Glu Ala Glu Leu His Ile Ser Tyr Arg Trp Asp Pro
65 70 75 80
Asn Leu Lys Gly Leu Met Arg Pro Ala Asn Ser Leu Leu Ser Thr Val
85 90 95
Lys Gln Asp Phe Pro Asp Ile Arg Gln Lys Pro Pro Ile Phe Gly Pro
100 105 110
Ile Phe Thr Asn Ile Asn Leu Met Gly Ile Ala Pro Ile Cys Val Met
115 120 125
Ala Lys Arg Lys Asn Gly Thr Asn Val Gly Thr Leu Pro Ser Thr Val
130 135 140
Cys Asn Val Thr Phe Thr Val Asp Ser Asn Gln Gln Thr Tyr Gln Thr
145 150 155 160
Tyr Thr His Asn Gln Phe Arg His Gln Pro Arg Phe Pro Lys Pro Pro
165 170 175
Asn Ile Thr Phe Pro Gln Gly Thr Leu Leu Asp Lys Ser Ser Arg Phe
180 185 190
Cys Gln Gly Arg Pro Ser Ser Cys Ser Thr Arg Asn Phe Trp Phe Arg
195 200 205
Pro Ala Asp Tyr Asn Gln Cys Leu Gln Ile Ser Asn Leu Ser Ser Thr
210 215 220
Ala Glu Trp Val Leu Leu Asp Gln Thr Arg Asn Ser Leu Phe Trp Glu
225 230 235 240
Asn Lys Thr Lys Gly Ala Asn Gln Ser Gln Thr Pro Cys Val Gln Val
245 250 255
Leu Ala Gly Met Thr Ile Ala Thr Ser Tyr Leu Gly Ile Ser Ala Val
260 265 270
Ser Glu Phe Phe Gly Thr Ser Leu Thr Pro Leu Phe His Phe His Ile
275 280 285
Ser Thr Cys Leu Lys Thr Gln Gly Ala Phe Tyr Ile Cys Gly Gln Ser
290 295 300
Ile His Gln Cys Leu Pro Ser Asn Trp Thr Gly Thr Cys Thr Ile Gly
305 310 315 320
Tyr Val Thr Pro Asp Ile Phe Ile Ala Pro Gly Asn Leu Ser Leu Pro
325 330 335
Ile Pro Ile Tyr Gly Asn Ser Pro Leu Pro Arg Val Arg Arg Ala Ile
340 345 350
His Phe Ile Pro Leu Leu Ala Gly Leu Gly Ile Leu Ala Gly Thr Gly
355 360 365
Thr Gly Ile Ala Gly Ile Thr Lys Ala Ser Leu Thr Tyr Ser Gln Leu
370 375 380
Ser Lys Glu Ile Ala Asn Asn Ile Asp Thr Met Ala Lys Ala Leu Thr
385 390 395 400
Thr Met Gln Glu Gln Ile Asp Ser Leu Ala Ala Val Val Leu Gln Asn
405 410 415
Arg Arg Gly Leu Asp Met Leu Thr Ala Ala Gln Gly Gly Ile Cys Leu
420 425 430
Ala Leu Asp Glu Lys Cys Cys Phe Trp Val Asn Gln Ser Gly Lys Val
435 440 445
Gln Asp Asn Ile Arg Gln Leu Leu Asn Gln Ala Ser Ser Leu Arg Glu
450 455 460
Arg Ala Thr Gln Gly Trp Leu Asn Trp Glu Gly Thr Trp Lys Trp Phe
465 470 475 480
Ser Trp Val Leu Pro Leu Thr Gly Pro Leu Val Ser Leu Leu Leu Leu
485 490 495
Leu Leu Phe Gly Pro Cys Leu Leu Asn Leu Ile Thr Gln Phe Val Ser
500 505 510
Ser Arg Leu Gln Ala Ile Lys Leu Gln Thr Asn Leu Ser Ala Gly Arg
515 520 525
His Pro Arg Asn Ile Gln Glu Ser Pro Phe
530 535
<210> 12
<211> 1017
<212> PRT
<213> 智人（Homo sapiens）
<400> 12
Met Val Phe Ser Val Arg Gln Cys Gly His Val Gly Arg Thr Glu Glu
1 5 10 15
Val Leu Leu Thr Phe Lys Ile Phe Leu Val Ile Ile Cys Leu His Val
20 25 30
Val Leu Val Thr Ser Leu Glu Glu Asp Thr Asp Asn Ser Ser Leu Ser
35 40 45
Pro Pro Pro Ala Lys Leu Ser Val Val Ser Phe Ala Pro Ser Ser Asn
50 55 60
Gly Thr Pro Glu Val Glu Thr Thr Ser Leu Asn Asp Val Thr Leu Ser
65 70 75 80
Leu Leu Pro Ser Asn Glu Thr Glu Lys Thr Lys Ile Thr Ile Val Lys
85 90 95
Thr Phe Asn Ala Ser Gly Val Lys Pro Gln Arg Asn Ile Cys Asn Leu
100 105 110
Ser Ser Ile Cys Asn Asp Ser Ala Phe Phe Arg Gly Glu Ile Met Phe
115 120 125
Gln Tyr Asp Lys Glu Ser Thr Val Pro Gln Asn Gln His Ile Thr Asn
130 135 140
Gly Thr Leu Thr Gly Val Leu Ser Leu Ser Glu Leu Lys Arg Ser Glu
145 150 155 160
Leu Asn Lys Thr Leu Gln Thr Leu Ser Glu Thr Tyr Phe Ile Met Cys
165 170 175
Ala Thr Ala Glu Ala Gln Ser Thr Leu Asn Cys Thr Phe Thr Ile Lys
180 185 190
Leu Asn Asn Thr Met Asn Ala Cys Ala Val Ile Ala Ala Leu Glu Arg
195 200 205
Val Lys Ile Arg Pro Met Glu His Cys Cys Cys Ser Val Arg Ile Pro
210 215 220
Cys Pro Ser Ser Pro Glu Glu Leu Glu Lys Leu Gln Cys Asp Leu Gln
225 230 235 240
Asp Pro Ile Val Cys Leu Ala Asp His Pro Arg Gly Pro Pro Phe Ser
245 250 255
Ser Ser Gln Ser Ile Pro Val Val Pro Arg Ala Thr Val Leu Ser Gln
260 265 270
Val Pro Lys Ala Thr Ser Phe Ala Glu Pro Pro Asp Tyr Ser Pro Val
275 280 285
Thr His Asn Val Pro Ser Pro Ile Gly Glu Ile Gln Pro Leu Ser Pro
290 295 300
Gln Pro Ser Ala Pro Ile Ala Ser Ser Pro Ala Ile Asp Met Pro Pro
305 310 315 320
Gln Ser Glu Thr Ile Ser Ser Pro Met Pro Gln Thr His Val Ser Gly
325 330 335
Thr Pro Pro Pro Val Lys Ala Ser Phe Ser Ser Pro Thr Val Ser Ala
340 345 350
Pro Ala Asn Val Asn Thr Thr Ser Ala Pro Pro Val Gln Thr Asp Ile
355 360 365
Val Asn Thr Ser Ser Ile Ser Asp Leu Glu Asn Gln Val Leu Gln Met
370 375 380
Glu Lys Ala Leu Ser Leu Gly Ser Leu Glu Pro Asn Leu Ala Gly Glu
385 390 395 400
Met Ile Asn Gln Val Ser Arg Leu Leu His Ser Pro Pro Asp Met Leu
405 410 415
Ala Pro Leu Ala Gln Arg Leu Leu Lys Val Val Asp Asp Ile Gly Leu
420 425 430
Gln Leu Asn Phe Ser Asn Thr Thr Ile Ser Leu Thr Ser Pro Ser Leu
435 440 445
Ala Leu Ala Val Ile Arg Val Asn Ala Ser Ser Phe Asn Thr Thr Thr
450 455 460
Phe Val Ala Gln Asp Pro Ala Asn Leu Gln Val Ser Leu Glu Thr Gln
465 470 475 480
Ala Pro Glu Asn Ser Ile Gly Thr Ile Thr Leu Pro Ser Ser Leu Met
485 490 495
Asn Asn Leu Pro Ala His Asp Met Glu Leu Ala Ser Arg Val Gln Phe
500 505 510
Asn Phe Phe Glu Thr Pro Ala Leu Phe Gln Asp Pro Ser Leu Glu Asn
515 520 525
Leu Ser Leu Ile Ser Tyr Val Ile Ser Ser Ser Val Ala Asn Leu Thr
530 535 540
Val Arg Asn Leu Thr Arg Asn Val Thr Val Thr Leu Lys His Ile Asn
545 550 555 560
Pro Ser Gln Asp Glu Leu Thr Val Arg Cys Val Phe Trp Asp Leu Gly
565 570 575
Arg Asn Gly Gly Arg Gly Gly Trp Ser Asp Asn Gly Cys Ser Val Lys
580 585 590
Asp Arg Arg Leu Asn Glu Thr Ile Cys Thr Cys Ser His Leu Thr Ser
595 600 605
Phe Gly Val Leu Leu Asp Leu Ser Arg Thr Ser Val Leu Pro Ala Gln
610 615 620
Met Met Ala Leu Thr Phe Ile Thr Tyr Ile Gly Cys Gly Leu Ser Ser
625 630 635 640
Ile Phe Leu Ser Val Thr Leu Val Thr Tyr Ile Ala Phe Glu Lys Ile
645 650 655
Arg Arg Asp Tyr Pro Ser Lys Ile Leu Ile Gln Leu Cys Ala Ala Leu
660 665 670
Leu Leu Leu Asn Leu Val Phe Leu Leu Asp Ser Trp Ile Ala Leu Tyr
675 680 685
Lys Met Gln Gly Leu Cys Ile Ser Val Ala Val Phe Leu His Tyr Phe
690 695 700
Leu Leu Val Ser Phe Thr Trp Met Gly Leu Glu Ala Phe His Met Tyr
705 710 715 720
Leu Ala Leu Val Lys Val Phe Asn Thr Tyr Ile Arg Lys Tyr Ile Leu
725 730 735
Lys Phe Cys Ile Val Gly Trp Gly Val Pro Ala Val Val Val Thr Ile
740 745 750
Ile Leu Thr Ile Ser Pro Asp Asn Tyr Gly Leu Gly Ser Tyr Gly Lys
755 760 765
Phe Pro Asn Gly Ser Pro Asp Asp Phe Cys Trp Ile Asn Asn Asn Ala
770 775 780
Val Phe Tyr Ile Thr Val Val Gly Tyr Phe Cys Val Ile Phe Leu Leu
785 790 795 800
Asn Val Ser Met Phe Ile Val Val Leu Val Gln Leu Cys Arg Ile Lys
805 810 815
Lys Lys Lys Gln Leu Gly Ala Gln Arg Lys Thr Ser Ile Gln Asp Leu
820 825 830
Arg Ser Ile Ala Gly Leu Thr Phe Leu Leu Gly Ile Thr Trp Gly Phe
835 840 845
Ala Phe Phe Ala Trp Gly Pro Val Asn Val Thr Phe Met Tyr Leu Phe
850 855 860
Ala Ile Phe Asn Thr Leu Gln Gly Phe Phe Ile Phe Ile Phe Tyr Cys
865 870 875 880
Val Ala Lys Glu Asn Val Arg Lys Gln Trp Arg Arg Tyr Leu Cys Cys
885 890 895
Gly Lys Leu Arg Leu Ala Glu Asn Ser Asp Trp Ser Lys Thr Ala Thr
900 905 910
Asn Gly Leu Lys Lys Gln Thr Val Asn Gln Gly Val Ser Ser Ser Ser
915 920 925
Asn Ser Leu Gln Ser Ser Ser Asn Ser Thr Asn Ser Thr Thr Leu Leu
930 935 940
Val Asn Asn Asp Cys Ser Val His Ala Ser Gly Asn Gly Asn Ala Ser
945 950 955 960
Thr Glu Arg Asn Gly Val Ser Phe Ser Val Gln Asn Gly Asp Val Cys
965 970 975
Leu His Asp Phe Thr Gly Lys Gln His Met Phe Asn Glu Lys Glu Asp
980 985 990
Ser Cys Asn Gly Lys Gly Arg Met Ala Leu Arg Arg Thr Ser Lys Arg
995 1000 1005
Gly Ser Leu His Phe Ile Glu Gln Met
1010 1015
<210> 13
<211> 775
<212> PRT
<213> 智人（Homo sapiens）
<400> 13
Met Glu Pro Pro Tyr Ser Leu Thr Ala His Tyr Asp Glu Phe Gln Glu
1 5 10 15
Val Lys Tyr Val Ser Arg Cys Gly Ala Gly Gly Ala Arg Gly Ala Ser
20 25 30
Leu Pro Pro Gly Phe Pro Leu Gly Ala Ala Arg Ser Ala Thr Gly Ala
35 40 45
Arg Ser Gly Leu Pro Arg Trp Asn Arg Arg Glu Val Cys Leu Leu Ser
50 55 60
Gly Leu Val Phe Ala Ala Gly Leu Cys Ala Ile Leu Ala Ala Met Leu
65 70 75 80
Ala Leu Lys Tyr Leu Gly Pro Val Ala Ala Gly Gly Gly Ala Cys Pro
85 90 95
Glu Gly Cys Pro Glu Arg Lys Ala Phe Ala Arg Ala Ala Arg Phe Leu
100 105 110
Ala Ala Asn Leu Asp Ala Ser Ile Asp Pro Cys Gln Asp Phe Tyr Ser
115 120 125
Phe Ala Cys Gly Gly Trp Leu Arg Arg His Ala Ile Pro Asp Asp Lys
130 135 140
Leu Thr Tyr Gly Thr Ile Ala Ala Ile Gly Glu Gln Asn Glu Glu Arg
145 150 155 160
Leu Arg Arg Leu Leu Ala Arg Pro Gly Gly Gly Pro Gly Gly Ala Ala
165 170 175
Gln Arg Lys Val Arg Ala Phe Phe Arg Ser Cys Leu Asp Met Arg Glu
180 185 190
Ile Glu Arg Leu Gly Pro Arg Pro Met Leu Glu Val Ile Glu Asp Cys
195 200 205
Gly Gly Trp Asp Leu Gly Gly Ala Glu Glu Arg Pro Gly Val Ala Ala
210 215 220
Arg Trp Asp Leu Asn Arg Leu Leu Tyr Lys Ala Gln Gly Val Tyr Ser
225 230 235 240
Ala Ala Ala Leu Phe Ser Leu Thr Val Ser Leu Asp Asp Arg Asn Ser
245 250 255
Ser Arg Tyr Val Ile Arg Ile Asp Gln Asp Gly Leu Thr Leu Pro Glu
260 265 270
Arg Thr Leu Tyr Leu Ala Gln Asp Glu Asp Ser Glu Lys Ile Leu Ala
275 280 285
Ala Tyr Arg Val Phe Met Glu Arg Val Leu Ser Leu Leu Gly Ala Asp
290 295 300
Ala Val Glu Gln Lys Ala Gln Glu Ile Leu Gln Val Glu Gln Gln Leu
305 310 315 320
Ala Asn Ile Thr Val Ser Glu His Asp Asp Leu Arg Arg Asp Val Ser
325 330 335
Ser Met Tyr Asn Lys Val Thr Leu Gly Gln Leu Gln Lys Ile Thr Pro
340 345 350
His Leu Arg Trp Lys Trp Leu Leu Asp Gln Ile Phe Gln Glu Asp Phe
355 360 365
Ser Glu Glu Glu Glu Val Val Leu Leu Ala Thr Asp Tyr Met Gln Gln
370 375 380
Val Ser Gln Leu Ile Arg Ser Thr Pro His Arg Val Leu His Asn Tyr
385 390 395 400
Leu Val Trp Arg Val Val Val Val Leu Ser Glu His Leu Ser Pro Pro
405 410 415
Phe Arg Glu Ala Leu His Glu Leu Ala Gln Glu Met Glu Gly Ser Asp
420 425 430
Lys Pro Gln Glu Leu Ala Arg Val Cys Leu Gly Gln Ala Asn Arg His
435 440 445
Phe Gly Met Ala Leu Gly Ala Leu Phe Val His Glu His Phe Ser Ala
450 455 460
Ala Ser Lys Ala Lys Val Gln Gln Leu Val Glu Asp Ile Lys Tyr Ile
465 470 475 480
Leu Gly Gln Arg Leu Glu Glu Leu Asp Trp Met Asp Ala Glu Thr Arg
485 490 495
Ala Ala Ala Arg Ala Lys Leu Gln Tyr Met Met Val Met Val Gly Tyr
500 505 510
Pro Asp Phe Leu Leu Lys Pro Asp Ala Val Asp Lys Glu Tyr Glu Phe
515 520 525
Glu Val His Glu Lys Thr Tyr Phe Lys Asn Ile Leu Asn Ser Ile Arg
530 535 540
Phe Ser Ile Gln Leu Ser Val Lys Lys Ile Arg Gln Glu Val Asp Lys
545 550 555 560
Ser Thr Trp Leu Leu Pro Pro Gln Ala Leu Asn Ala Tyr Tyr Leu Pro
565 570 575
Asn Lys Asn Gln Met Val Phe Pro Ala Gly Ile Leu Gln Pro Thr Leu
580 585 590
Tyr Asp Pro Asp Phe Pro Gln Ser Leu Asn Tyr Gly Gly Ile Gly Thr
595 600 605
Ile Ile Gly His Glu Leu Thr His Gly Tyr Asp Asp Trp Gly Gly Gln
610 615 620
Tyr Asp Arg Ser Gly Asn Leu Leu His Trp Trp Thr Glu Ala Ser Tyr
625 630 635 640
Ser Arg Phe Leu Arg Lys Ala Glu Cys Ile Val Arg Leu Tyr Asp Asn
645 650 655
Phe Thr Val Tyr Asn Gln Arg Val Asn Gly Lys His Thr Leu Gly Glu
660 665 670
Asn Ile Ala Asp Met Gly Gly Leu Lys Leu Ala Tyr His Ala Tyr Gln
675 680 685
Lys Trp Val Arg Glu His Gly Pro Glu His Pro Leu Pro Arg Leu Lys
690 695 700
Tyr Thr His Asp Gln Leu Phe Phe Ile Ala Phe Ala Gln Asn Trp Cys
705 710 715 720
Ile Lys Arg Arg Ser Gln Ser Ile Tyr Leu Gln Val Leu Thr Asp Lys
725 730 735
His Ala Pro Glu His Tyr Arg Val Leu Gly Ser Val Ser Gln Phe Glu
740 745 750
Glu Phe Gly Arg Ala Phe His Cys Pro Lys Asp Ser Pro Met Asn Pro
755 760 765
Ala His Lys Cys Ser Val Trp
770 775
<210> 14
<211> 529
<212> PRT
<213> 智人（Homo sapiens）
<400> 14
Met Gly Pro Ser Cys Pro Val Phe Leu Ser Phe Thr Lys Leu Ser Leu
1 5 10 15
Trp Trp Leu Leu Leu Thr Pro Ala Gly Gly Glu Glu Ala Lys Arg Pro
20 25 30
Pro Pro Arg Ala Pro Gly Asp Pro Leu Ser Ser Pro Ser Pro Thr Ala
35 40 45
Leu Pro Gln Gly Gly Ser His Thr Glu Thr Glu Asp Arg Leu Phe Lys
50 55 60
His Leu Phe Arg Gly Tyr Asn Arg Trp Ala Arg Pro Val Pro Asn Thr
65 70 75 80
Ser Asp Val Val Ile Val Arg Phe Gly Leu Ser Ile Ala Gln Leu Ile
85 90 95
Asp Val Asp Glu Lys Asn Gln Met Met Thr Thr Asn Val Trp Leu Lys
100 105 110
Gln Glu Trp Ser Asp Tyr Lys Leu Arg Trp Asn Pro Thr Asp Phe Gly
115 120 125
Asn Ile Thr Ser Leu Arg Val Pro Ser Glu Met Ile Trp Ile Pro Asp
130 135 140
Ile Val Leu Tyr Asn Asn Ala Asp Gly Glu Phe Ala Val Thr His Met
145 150 155 160
Thr Lys Ala His Leu Phe Ser Thr Gly Thr Val His Trp Val Pro Pro
165 170 175
Ala Ile Tyr Lys Ser Ser Cys Ser Ile Asp Val Thr Phe Phe Pro Phe
180 185 190
Asp Gln Gln Asn Cys Lys Met Lys Phe Gly Ser Trp Thr Tyr Asp Lys
195 200 205
Ala Lys Ile Asp Leu Glu Gln Met Glu Gln Thr Val Asp Leu Lys Asp
210 215 220
Tyr Trp Glu Ser Gly Glu Trp Ala Ile Val Asn Ala Thr Gly Thr Tyr
225 230 235 240
Asn Ser Lys Lys Tyr Asp Cys Cys Ala Glu Ile Tyr Pro Asp Val Thr
245 250 255
Tyr Ala Phe Val Ile Arg Arg Leu Pro Leu Phe Tyr Thr Ile Asn Leu
260 265 270
Ile Ile Pro Cys Leu Leu Ile Ser Cys Leu Thr Val Leu Val Phe Tyr
275 280 285
Leu Pro Ser Asp Cys Gly Glu Lys Ile Thr Leu Cys Ile Ser Val Leu
290 295 300
Leu Ser Leu Thr Val Phe Leu Leu Leu Ile Thr Glu Ile Ile Pro Ser
305 310 315 320
Thr Ser Leu Val Ile Pro Leu Ile Gly Glu Tyr Leu Leu Phe Thr Met
325 330 335
Ile Phe Val Thr Leu Ser Ile Val Ile Thr Val Phe Val Leu Asn Val
340 345 350
His His Arg Ser Pro Ser Thr His Thr Met Pro His Trp Val Arg Gly
355 360 365
Ala Leu Leu Gly Cys Val Pro Arg Trp Leu Leu Met Asn Arg Pro Pro
370 375 380
Pro Pro Val Glu Leu Cys His Pro Leu Arg Leu Lys Leu Ser Pro Ser
385 390 395 400
Tyr His Trp Leu Glu Ser Asn Val Asp Ala Glu Glu Arg Glu Val Val
405 410 415
Val Glu Glu Glu Asp Arg Trp Ala Cys Ala Gly His Val Ala Pro Ser
420 425 430
Val Gly Thr Leu Cys Ser His Gly His Leu His Ser Gly Ala Ser Gly
435 440 445
Pro Lys Ala Glu Ala Leu Leu Gln Glu Gly Glu Leu Leu Leu Ser Pro
450 455 460
His Met Gln Lys Ala Leu Glu Gly Val His Tyr Ile Ala Asp His Leu
465 470 475 480
Arg Ser Glu Asp Ala Asp Ser Ser Val Lys Glu Asp Trp Lys Tyr Val
485 490 495
Ala Met Val Ile Asp Arg Ile Phe Leu Trp Leu Phe Ile Ile Val Cys
500 505 510
Phe Leu Gly Thr Ile Gly Leu Phe Leu Pro Pro Phe Leu Ala Gly Met
515 520 525
Ile
<210> 15
<211> 537
<212> PRT
<213> 智人（Homo sapiens）
<400> 15
Met Pro His Leu Met Glu Arg Met Val Gly Ser Gly Leu Leu Trp Leu
1 5 10 15
Ala Leu Val Ser Cys Ile Leu Thr Gln Ala Ser Ala Val Gln Arg Gly
20 25 30
Tyr Gly Asn Pro Ile Glu Ala Ser Ser Tyr Gly Leu Asp Leu Asp Cys
35 40 45
Gly Ala Pro Gly Thr Pro Glu Ala His Val Cys Phe Asp Pro Cys Gln
50 55 60
Asn Tyr Thr Leu Leu Asp Glu Pro Phe Arg Ser Thr Glu Asn Ser Ala
65 70 75 80
Gly Ser Gln Gly Cys Asp Lys Asn Met Ser Gly Trp Tyr Arg Phe Val
85 90 95
Gly Glu Gly Gly Val Arg Met Ser Glu Thr Cys Val Gln Val His Arg
100 105 110
Cys Gln Thr Asp Ala Pro Met Trp Leu Asn Gly Thr His Pro Ala Leu
115 120 125
Gly Asp Gly Ile Thr Asn His Thr Ala Cys Ala His Trp Ser Gly Asn
130 135 140
Cys Cys Phe Trp Lys Thr Glu Val Leu Val Lys Ala Cys Pro Gly Gly
145 150 155 160
Tyr His Val Tyr Arg Leu Glu Gly Thr Pro Trp Cys Asn Leu Arg Tyr
165 170 175
Cys Thr Val Pro Arg Asp Pro Ser Thr Val Glu Asp Lys Cys Glu Lys
180 185 190
Ala Cys Arg Pro Glu Glu Glu Cys Leu Ala Leu Asn Ser Thr Trp Gly
195 200 205
Cys Phe Cys Arg Gln Asp Leu Asn Ser Ser Asp Val His Ser Leu Gln
210 215 220
Pro Gln Leu Asp Cys Gly Pro Arg Glu Ile Lys Val Lys Val Asp Lys
225 230 235 240
Cys Leu Leu Gly Gly Leu Gly Leu Gly Glu Glu Val Ile Ala Tyr Leu
245 250 255
Arg Asp Pro Asn Cys Ser Ser Ile Leu Gln Thr Glu Glu Arg Asn Trp
260 265 270
Val Ser Val Thr Ser Pro Val Gln Ala Ser Ala Cys Arg Asn Ile Leu
275 280 285
Glu Arg Asn Gln Thr His Ala Ile Tyr Lys Asn Thr Leu Ser Leu Val
290 295 300
Asn Asp Phe Ile Ile Arg Asp Thr Ile Leu Asn Ile Asn Phe Gln Cys
305 310 315 320
Ala Tyr Pro Leu Asp Met Lys Val Ser Leu Gln Ala Ala Leu Gln Pro
325 330 335
Ile Val Ser Ser Leu Asn Val Ser Val Asp Gly Asn Gly Glu Phe Ile
340 345 350
Val Arg Met Ala Leu Phe Gln Asp Gln Asn Tyr Thr Asn Pro Tyr Glu
355 360 365
Gly Asp Ala Val Glu Leu Ser Val Glu Ser Val Leu Tyr Val Gly Ala
370 375 380
Ile Leu Glu Gln Gly Asp Thr Ser Arg Phe Asn Leu Val Leu Arg Asn
385 390 395 400
Cys Tyr Ala Thr Pro Thr Glu Asp Lys Ala Asp Leu Val Lys Tyr Phe
405 410 415
Ile Ile Arg Asn Ser Cys Ser Asn Gln Arg Asp Ser Thr Ile His Val
420 425 430
Glu Glu Asn Gly Gln Ser Ser Glu Ser Arg Phe Ser Val Gln Met Phe
435 440 445
Met Phe Ala Gly His Tyr Asp Leu Val Phe Leu His Cys Glu Ile His
450 455 460
Leu Cys Asp Ser Leu Asn Glu Gln Cys Gln Pro Ser Cys Ser Arg Ser
465 470 475 480
Gln Val Arg Ser Glu Val Pro Ala Ile Asp Leu Ala Arg Val Leu Asp
485 490 495
Leu Gly Pro Ile Thr Arg Arg Gly Ala Gln Ser Pro Gly Val Met Asn
500 505 510
Gly Thr Pro Ser Thr Ala Gly Phe Leu Val Ala Trp Pro Met Val Leu
515 520 525
Leu Thr Val Leu Leu Ala Trp Leu Phe
530 535
<210> 16
<211> 426
<212> PRT
<213> 智人（Homo sapiens）
<400> 16
Met Gly Pro Leu Pro Ala Pro Ser Cys Thr Gln Arg Ile Thr Trp Lys
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 Glu Val Thr Ile Glu Ala Gln Pro Pro Lys Val Ser Glu Gly
35 40 45
Lys Asp Val Leu Leu Leu Val His Asn Leu Pro Gln Asn Leu Pro Gly
50 55 60
Tyr Phe Trp Tyr Lys Gly Glu Met Thr Asp Leu Tyr His Tyr Ile Ile
65 70 75 80
Ser Tyr Ile Val Asp Gly Lys Ile Ile Ile Tyr Gly Pro Ala Tyr Ser
85 90 95
Gly Arg Glu Thr Val Tyr Ser Asn Ala Ser Leu Leu Ile Gln Asn Val
100 105 110
Thr Arg Lys Asp Ala Gly Thr Tyr Thr Leu His Ile Ile Lys Arg Gly
115 120 125
Asp Glu Thr Arg Glu Glu Ile Arg His Phe Thr Phe Thr Leu Tyr Leu
130 135 140
Glu Thr Pro Lys Pro Tyr Ile Ser Ser Ser Asn Leu Asn Pro Arg Glu
145 150 155 160
Ala Met Glu Ala Val Arg Leu Ile Cys Asp Pro Glu Thr Leu Asp Ala
165 170 175
Ser Tyr Leu Trp Trp Met Asn Gly Gln Ser Leu Pro Val Thr His Arg
180 185 190
Leu Gln Leu Ser Lys Thr Asn Arg Thr Leu Tyr Leu Phe Gly Val Thr
195 200 205
Lys Tyr Ile Ala Gly Pro Tyr Glu Cys Glu Ile Arg Asn Pro Val Ser
210 215 220
Ala Ser Arg Ser Asp Pro Val Thr Leu Asn Leu Leu Pro Lys Leu Pro
225 230 235 240
Ile Pro Tyr Ile Thr Ile Asn Asn Leu Asn Pro Arg Glu Asn Lys Asp
245 250 255
Val Leu Ala Phe Thr Cys Glu Pro Lys Ser Glu Asn Tyr Thr Tyr Ile
260 265 270
Trp Trp Leu Asn Gly Gln Ser Leu Pro Val Ser Pro Gly Val Lys Arg
275 280 285
Pro Ile Glu Asn Arg Ile Leu Ile Leu Pro Ser Val Thr Arg Asn Glu
290 295 300
Thr Gly Pro Tyr Gln Cys Glu Ile Arg Asp Arg Tyr Gly Gly Leu Arg
305 310 315 320
Ser Asn Pro Val Ile Leu Asn Val Leu Tyr Gly Pro Asp Leu Pro Arg
325 330 335
Ile Tyr Pro Ser Phe Thr Tyr Tyr Arg Ser Gly Glu Asn Leu Asp Leu
340 345 350
Ser Cys Phe Thr Glu Ser Asn Pro Pro Ala Glu Tyr Phe Trp Thr Ile
355 360 365
Asn Gly Lys Phe Gln Gln Ser Gly Gln Lys Leu Phe Ile Pro Gln Ile
370 375 380
Thr Arg Asn His Ser Gly Leu Tyr Ala Cys Ser Val His Asn Ser Ala
385 390 395 400
Thr Gly Lys Glu Ile Ser Lys Ser Met Thr Val Lys Val Ser Gly Pro
405 410 415
Cys His Gly Asp Leu Thr Glu Ser Gln Ser
420 425
<210> 17
<211> 328
<212> PRT
<213> 智人（Homo sapiens）
<400> 17
Met Glu Lys Ser Ile Trp Leu Leu Ala Cys Leu Ala Trp Val Leu Pro
1 5 10 15
Thr Gly Ser Phe Val Arg Thr Lys Ile Asp Thr Thr Glu Asn Leu Leu
20 25 30
Asn Thr Glu Val His Ser Ser Pro Ala Gln Arg Trp Ser Met Gln Val
35 40 45
Pro Pro Glu Val Ser Ala Glu Ala Gly Asp Ala Ala Val Leu Pro Cys
50 55 60
Thr Phe Thr His Pro His Arg His Tyr Asp Gly Pro Leu Thr Ala Ile
65 70 75 80
Trp Arg Ala Gly Glu Pro Tyr Ala Gly Pro Gln Val Phe Arg Cys Ala
85 90 95
Ala Ala Arg Gly Ser Glu Leu Cys Gln Thr Ala Leu Ser Leu His Gly
100 105 110
Arg Phe Arg Leu Leu Gly Asn Pro Arg Arg Asn Asp Leu Ser Leu Arg
115 120 125
Val Glu Arg Leu Ala Leu Ala Asp Asp Arg Arg Tyr Phe Cys Arg Val
130 135 140
Glu Phe Ala Gly Asp Val His Asp Arg Tyr Glu Ser Arg His Gly Val
145 150 155 160
Arg Leu His Val Thr Ala Ala Pro Arg Ile Val Asn Ile Ser Val Leu
165 170 175
Pro Ser Pro Ala His Ala Phe Arg Ala Leu Cys Thr Ala Glu Gly Glu
180 185 190
Pro Pro Pro Ala Leu Ala Trp Ser Gly Pro Ala Leu Gly Asn Ser Leu
195 200 205
Ala Ala Val Arg Ser Pro Arg Glu Gly His Gly His Leu Val Thr Ala
210 215 220
Glu Leu Pro Ala Leu Thr His Asp Gly Arg Tyr Thr Cys Thr Ala Ala
225 230 235 240
Asn Ser Leu Gly Arg Ser Glu Ala Ser Val Tyr Leu Phe Arg Phe His
245 250 255
Gly Ala Ser Gly Ala Ser Thr Val Ala Leu Leu Leu Gly Ala Leu Gly
260 265 270
Phe Lys Ala Leu Leu Leu Leu Gly Val Leu Ala Ala Arg Ala Ala Arg
275 280 285
Arg Arg Pro Glu His Leu Asp Thr Pro Asp Thr Pro Pro Arg Ser Gln
290 295 300
Ala Gln Glu Ser Asn Tyr Glu Asn Leu Ser Gln Met Asn Pro Arg Ser
305 310 315 320
Pro Pro Ala Thr Met Cys Ser Pro
325
<210> 18
<211> 620
<212> PRT
<213> 智人（Homo sapiens）
<400> 18
Met Ser Lys Ser Lys Cys Ser Val Gly Leu Met Ser Ser Val Val Ala
1 5 10 15
Pro Ala Lys Glu Pro Asn Ala Val Gly Pro Lys Glu Val Glu Leu Ile
20 25 30
Leu Val Lys Glu Gln Asn Gly Val Gln Leu Thr Ser Ser Thr Leu Thr
35 40 45
Asn Pro Arg Gln Ser Pro Val Glu Ala Gln Asp Arg Glu Thr Trp Gly
50 55 60
Lys Lys Ile Asp Phe Leu Leu Ser Val Ile Gly Phe Ala Val Asp Leu
65 70 75 80
Ala Asn Val Trp Arg Phe Pro Tyr Leu Cys Tyr Lys Asn Gly Gly Gly
85 90 95
Ala Phe Leu Val Pro Tyr Leu Leu Phe Met Val Ile Ala Gly Met Pro
100 105 110
Leu Phe Tyr Met Glu Leu Ala Leu Gly Gln Phe Asn Arg Glu Gly Ala
115 120 125
Ala Gly Val Trp Lys Ile Cys Pro Ile Leu Lys Gly Val Gly Phe Thr
130 135 140
Val Ile Leu Ile Ser Leu Tyr Val Gly Phe Phe Tyr Asn Val Ile Ile
145 150 155 160
Ala Trp Ala Leu His Tyr Leu Phe Ser Ser Phe Thr Thr Glu Leu Pro
165 170 175
Trp Ile His Cys Asn Asn Ser Trp Asn Ser Pro Asn Cys Ser Asp Ala
180 185 190
His Pro Gly Asp Ser Ser Gly Asp Ser Ser Gly Leu Asn Asp Thr Phe
195 200 205
Gly Thr Thr Pro Ala Ala Glu Tyr Phe Glu Arg Gly Val Leu His Leu
210 215 220
His Gln Ser His Gly Ile Asp Asp Leu Gly Pro Pro Arg Trp Gln Leu
225 230 235 240
Thr Ala Cys Leu Val Leu Val Ile Val Leu Leu Tyr Phe Ser Leu Trp
245 250 255
Lys Gly Val Lys Thr Ser Gly Lys Val Val Trp Ile Thr Ala Thr Met
260 265 270
Pro Tyr Val Val Leu Thr Ala Leu Leu Leu Arg Gly Val Thr Leu Pro
275 280 285
Gly Ala Ile Asp Gly Ile Arg Ala Tyr Leu Ser Val Asp Phe Tyr Arg
290 295 300
Leu Cys Glu Ala Ser Val Trp Ile Asp Ala Ala Thr Gln Val Cys Phe
305 310 315 320
Ser Leu Gly Val Gly Phe Gly Val Leu Ile Ala Phe Ser Ser Tyr Asn
325 330 335
Lys Phe Thr Asn Asn Cys Tyr Arg Asp Ala Ile Val Thr Thr Ser Ile
340 345 350
Asn Ser Leu Thr Ser Phe Ser Ser Gly Phe Val Val Phe Ser Phe Leu
355 360 365
Gly Tyr Met Ala Gln Lys His Ser Val Pro Ile Gly Asp Val Ala Lys
370 375 380
Asp Gly Pro Gly Leu Ile Phe Ile Ile Tyr Pro Glu Ala Ile Ala Thr
385 390 395 400
Leu Pro Leu Ser Ser Ala Trp Ala Val Val Phe Phe Ile Met Leu Leu
405 410 415
Thr Leu Gly Ile Asp Ser Ala Met Gly Gly Met Glu Ser Val Ile Thr
420 425 430
Gly Leu Ile Asp Glu Phe Gln Leu Leu His Arg His Arg Glu Leu Phe
435 440 445
Thr Leu Phe Ile Val Leu Ala Thr Phe Leu Leu Ser Leu Phe Cys Val
450 455 460
Thr Asn Gly Gly Ile Tyr Val Phe Thr Leu Leu Asp His Phe Ala Ala
465 470 475 480
Gly Thr Ser Ile Leu Phe Gly Val Leu Ile Glu Ala Ile Gly Val Ala
485 490 495
Trp Phe Tyr Gly Val Gly Gln Phe Ser Asp Asp Ile Gln Gln Met Thr
500 505 510
Gly Gln Arg Pro Ser Leu Tyr Trp Arg Leu Cys Trp Lys Leu Val Ser
515 520 525
Pro Cys Phe Leu Leu Phe Val Val Val Val Ser Ile Val Thr Phe Arg
530 535 540
Pro Pro His Tyr Gly Ala Tyr Ile Phe Pro Asp Trp Ala Asn Ala Leu
545 550 555 560
Gly Trp Val Ile Ala Thr Ser Ser Met Ala Met Val Pro Ile Tyr Ala
565 570 575
Ala Tyr Lys Phe Cys Ser Leu Pro Gly Ser Phe Arg Glu Lys Leu Ala
580 585 590
Tyr Ala Ile Ala Pro Glu Lys Asp Arg Glu Leu Val Asp Arg Gly Glu
595 600 605
Val Arg Gln Phe Thr Leu Arg His Trp Leu Lys Val
610 615 620
<210> 19
<211> 398
<212> PRT
<213> 智人（Homo sapiens）
<400> 19
Met His Thr Val Ala Thr Ser Gly Pro Asn Ala Ser Trp Gly Ala Pro
1 5 10 15
Ala Asn Ala Ser Gly Cys Pro Gly Cys Gly Ala Asn Ala Ser Asp Gly
20 25 30
Pro Val Pro Ser Pro Arg Ala Val Asp Ala Trp Leu Val Pro Leu Phe
35 40 45
Phe Ala Ala Leu Met Leu Leu Gly Leu Val Gly Asn Ser Leu Val Ile
50 55 60
Tyr Val Ile Cys Arg His Lys Pro Met Arg Thr Val Thr Asn Phe Tyr
65 70 75 80
Ile Ala Asn Leu Ala Ala Thr Asp Val Thr Phe Leu Leu Cys Cys Val
85 90 95
Pro Phe Thr Ala Leu Leu Tyr Pro Leu Pro Gly Trp Val Leu Gly Asp
100 105 110
Phe Met Cys Lys Phe Val Asn Tyr Ile Gln Gln Val Ser Val Gln Ala
115 120 125
Thr Cys Ala Thr Leu Thr Ala Met Ser Val Asp Arg Trp Tyr Val Thr
130 135 140
Val Phe Pro Leu Arg Ala Leu His Arg Arg Thr Pro Arg Leu Ala Leu
145 150 155 160
Ala Val Ser Leu Ser Ile Trp Val Gly Ser Ala Ala Val Ser Ala Pro
165 170 175
Val Leu Ala Leu His Arg Leu Ser Pro Gly Pro Arg Ala Tyr Cys Ser
180 185 190
Glu Ala Phe Pro Ser Arg Ala Leu Glu Arg Ala Phe Ala Leu Tyr Asn
195 200 205
Leu Leu Ala Leu Tyr Leu Leu Pro Leu Leu Ala Thr Cys Ala Cys Tyr
210 215 220
Ala Ala Met Leu Arg His Leu Gly Arg Val Ala Val Arg Pro Ala Pro
225 230 235 240
Ala Asp Ser Ala Leu Gln Gly Gln Val Leu Ala Glu Arg Ala Gly Ala
245 250 255
Val Arg Ala Lys Val Ser Arg Leu Val Ala Ala Val Val Leu Leu Phe
260 265 270
Ala Ala Cys Trp Gly Pro Ile Gln Leu Phe Leu Val Leu Gln Ala Leu
275 280 285
Gly Pro Ala Gly Ser Trp His Pro Arg Ser Tyr Ala Ala Tyr Ala Leu
290 295 300
Lys Thr Trp Ala His Cys Met Ser Tyr Ser Asn Ser Ala Leu Asn Pro
305 310 315 320
Leu Leu Tyr Ala Phe Leu Gly Ser His Phe Arg Gln Ala Phe Arg Arg
325 330 335
Val Cys Pro Cys Ala Pro Arg Arg Pro Arg Arg Pro Arg Arg Pro Gly
340 345 350
Pro Ser Asp Pro Ala Ala Pro His Ala Glu Leu Leu Arg Leu Gly Ser
355 360 365
His Pro Ala Pro Ala Arg Ala Gln Lys Pro Gly Ser Ser Gly Leu Ala
370 375 380
Ala Arg Gly Leu Cys Val Leu Gly Glu Asp Asn Ala Pro Leu
385 390 395
<210> 20
<211> 431
<212> PRT
<213> 智人（Homo sapiens）
<400> 20
Met Gln Ala Leu Asn Ile Thr Pro Glu Gln Phe Ser Arg Leu Leu Arg
1 5 10 15
Asp His Asn Leu Thr Arg Glu Gln Phe Ile Ala Leu Tyr Arg Leu Arg
20 25 30
Pro Leu Val Tyr Thr Pro Glu Leu Pro Gly Arg Ala Lys Leu Ala Leu
35 40 45
Val Leu Thr Gly Val Leu Ile Phe Ala Leu Ala Leu Phe Gly Asn Ala
50 55 60
Leu Val Phe Tyr Val Val Thr Arg Ser Lys Ala Met Arg Thr Val Thr
65 70 75 80
Asn Ile Phe Ile Cys Ser Leu Ala Leu Ser Asp Leu Leu Ile Thr Phe
85 90 95
Phe Cys Ile Pro Val Thr Met Leu Gln Asn Ile Ser Asp Asn Trp Leu
100 105 110
Gly Gly Ala Phe Ile Cys Lys Met Val Pro Phe Val Gln Ser Thr Ala
115 120 125
Val Val Thr Glu Ile Leu Thr Met Thr Cys Ile Ala Val Glu Arg His
130 135 140
Gln Gly Leu Val His Pro Phe Lys Met Lys Trp Gln Tyr Thr Asn Arg
145 150 155 160
Arg Ala Phe Thr Met Leu Gly Val Val Trp Leu Val Ala Val Ile Val
165 170 175
Gly Ser Pro Met Trp His Val Gln Gln Leu Glu Ile Lys Tyr Asp Phe
180 185 190
Leu Tyr Glu Lys Glu His Ile Cys Cys Leu Glu Glu Trp Thr Ser Pro
195 200 205
Val His Gln Lys Ile Tyr Thr Thr Phe Ile Leu Val Ile Leu Phe Leu
210 215 220
Leu Pro Leu Met Val Met Leu Ile Leu Tyr Ser Lys Ile Gly Tyr Glu
225 230 235 240
Leu Trp Ile Lys Lys Arg Val Gly Asp Gly Ser Val Leu Arg Thr Ile
245 250 255
His Gly Lys Glu Met Ser Lys Ile Ala Arg Lys Lys Lys Arg Ala Val
260 265 270
Ile Met Met Val Thr Val Val Ala Leu Phe Ala Val Cys Trp Ala Pro
275 280 285
Phe His Val Val His Met Met Ile Glu Tyr Ser Asn Phe Glu Lys Glu
290 295 300
Tyr Asp Asp Val Thr Ile Lys Met Ile Phe Ala Ile Val Gln Ile Ile
305 310 315 320
Gly Phe Ser Asn Ser Ile Cys Asn Pro Ile Val Tyr Ala Phe Met Asn
325 330 335
Glu Asn Phe Lys Lys Asn Val Leu Ser Ala Val Cys Tyr Cys Ile Val
340 345 350
Asn Lys Thr Phe Ser Pro Ala Gln Arg His Gly Asn Ser Gly Ile Thr
355 360 365
Met Met Arg Lys Lys Ala Lys Phe Ser Leu Arg Glu Asn Pro Val Glu
370 375 380
Glu Thr Lys Gly Glu Ala Phe Ser Asp Gly Asn Ile Glu Val Lys Leu
385 390 395 400
Cys Glu Gln Thr Glu Glu Lys Lys Lys Leu Lys Arg His Leu Ala Leu
405 410 415
Phe Arg Ser Glu Leu Ala Glu Asn Ser Pro Leu Asp Ser Gly His
420 425 430
<210> 21
<211> 335
<212> PRT
<213> 智人（Homo sapiens）
<400> 21
Met Glu Ser Ser Phe Ser Phe Gly Val Ile Leu Ala Val Leu Ala Ser
1 5 10 15
Leu Ile Ile Ala Thr Asn Thr Leu Val Ala Val Ala Val Leu Leu Leu
20 25 30
Ile His Lys Asn Asp Gly Val Ser Leu Cys Phe Thr Leu Asn Leu Ala
35 40 45
Val Ala Asp Thr Leu Ile Gly Val Ala Ile Ser Gly Leu Leu Thr Asp
50 55 60
Gln Leu Ser Ser Pro Ser Arg Pro Thr Gln Lys Thr Leu Cys Ser Leu
65 70 75 80
Arg Met Ala Phe Val Thr Ser Ser Ala Ala Ala Ser Val Leu Thr Val
85 90 95
Met Leu Ile Thr Phe Asp Arg Tyr Leu Ala Ile Lys Gln Pro Phe Arg
100 105 110
Tyr Leu Lys Ile Met Ser Gly Phe Val Ala Gly Ala Cys Ile Ala Gly
115 120 125
Leu Trp Leu Val Ser Tyr Leu Ile Gly Phe Leu Pro Leu Gly Ile Pro
130 135 140
Met Phe Gln Gln Thr Ala Tyr Lys Gly Gln Cys Ser Phe Phe Ala Val
145 150 155 160
Phe His Pro His Phe Val Leu Thr Leu Ser Cys Val Gly Phe Phe Pro
165 170 175
Ala Met Leu Leu Phe Val Phe Phe Tyr Cys Asp Met Leu Lys Ile Ala
180 185 190
Ser Met His Ser Gln Gln Ile Arg Lys Met Glu His Ala Gly Ala Met
195 200 205
Ala Gly Gly Tyr Arg Ser Pro Arg Thr Pro Ser Asp Phe Lys Ala Leu
210 215 220
Arg Thr Val Ser Val Leu Ile Gly Ser Phe Ala Leu Ser Trp Thr Pro
225 230 235 240
Phe Leu Ile Thr Gly Ile Val Gln Val Ala Cys Gln Glu Cys His Leu
245 250 255
Tyr Leu Val Leu Glu Arg Tyr Leu Trp Leu Leu Gly Val Gly Asn Ser
260 265 270
Leu Leu Asn Pro Leu Ile Tyr Ala Tyr Trp Gln Lys Glu Val Arg Leu
275 280 285
Gln Leu Tyr His Met Ala Leu Gly Val Lys Lys Val Leu Thr Ser Phe
290 295 300
Leu Leu Phe Leu Ser Ala Arg Asn Cys Gly Pro Glu Arg Pro Arg Glu
305 310 315 320
Ser Ser Cys His Ile Val Thr Ile Ser Ser Ser Glu Phe Asp Gly
325 330 335
<210> 22
<211> 220
<212> PRT
<213> 智人（Homo sapiens）
<400> 22
Met Ala Ser Ala Gly Met Gln Ile Leu Gly Val Val Leu Thr Leu Leu
1 5 10 15
Gly Trp Val Asn Gly Leu Val Ser Cys Ala Leu Pro Met Trp Lys Val
20 25 30
Thr Ala Phe Ile Gly Asn Ser Ile Val Val Ala Gln Val Val Trp Glu
35 40 45
Gly Leu Trp Met Ser Cys Val Val Gln Ser Thr Gly Gln Met Gln Cys
50 55 60
Lys Val Tyr Asp Ser Leu Leu Ala Leu Pro Gln Asp Leu Gln Ala Ala
65 70 75 80
Arg Ala Leu Cys Val Ile Ala Leu Leu Val Ala Leu Phe Gly Leu Leu
85 90 95
Val Tyr Leu Ala Gly Ala Lys Cys Thr Thr Cys Val Glu Glu Lys Asp
100 105 110
Ser Lys Ala Arg Leu Val Leu Thr Ser Gly Ile Val Phe Val Ile Ser
115 120 125
Gly Val Leu Thr Leu Ile Pro Val Cys Trp Thr Ala His Ala Ile Ile
130 135 140
Arg Asp Phe Tyr Asn Pro Leu Val Ala Glu Ala Gln Lys Arg Glu Leu
145 150 155 160
Gly Ala Ser Leu Tyr Leu Gly Trp Ala Ala Ser Gly Leu Leu Leu Leu
165 170 175
Gly Gly Gly Leu Leu Cys Cys Thr Cys Pro Ser Gly Gly Ser Gln Gly
180 185 190
Pro Ser His Tyr Met Ala Arg Tyr Ser Thr Ser Ala Pro Ala Ile Ser
195 200 205
Arg Gly Pro Ser Glu Tyr Pro Thr Lys Asn Tyr Val
210 215 220
<210> 23
<211> 21
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 23
Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu
1 5 10 15
His Ala Ala Arg Pro
20
<210> 24
<211> 15
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 24
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
1 5 10 15
<210> 25
<211> 45
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 25
Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala
1 5 10 15
Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly
20 25 30
Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp
35 40 45
<210> 26
<211> 23
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 26
Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser
1 5 10 15
Leu Val Ile Thr Leu Tyr Cys
20
<210> 27
<211> 42
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 27
Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met
1 5 10 15
Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe
20 25 30
Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu
35 40
<210> 28
<211> 112
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 28
Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly
1 5 10 15
Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr
20 25 30
Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys
35 40 45
Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys
50 55 60
Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg
65 70 75 80
Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala
85 90 95
Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg
100 105 110
<210> 29
<211> 485
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 29
Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu
1 5 10 15
His Ala Ala Arg Pro Gln Ile Val Leu Thr Gln Ser Pro Ala Ile Met
20 25 30
Ser Ala Ser Leu Gly Glu Arg Val Thr Met Thr Cys Thr Ala Ser Ser
35 40 45
Val Val Ile Ser Thr Tyr Leu His Trp Tyr Gln Gln Lys Pro Gly Ser
50 55 60
Ser Pro Lys Leu Trp Ile Tyr Ser Thr Ser Asn Leu Ala Ser Gly Val
65 70 75 80
Pro Val Arg Phe Ser Gly Ser Gly Ser Gly Thr Ser Tyr Ser Leu Thr
85 90 95
Ile Ser Ser Met Glu Ala Glu Asp Ala Ala Thr Tyr Tyr Cys His Gln
100 105 110
Tyr His Arg Ser Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile
115 120 125
Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Gly
145 150 155 160
Ser Met Lys Ile Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr
165 170 175
Thr Met Asn Trp Val Lys Gln Ser His Gly Lys Asn Leu Glu Trp Ile
180 185 190
Gly Leu Ile Asn Pro Tyr Asn Gly Gly Ile Ser Tyr Asn Gln Lys Phe
195 200 205
Lys Asp Lys Ala Thr Leu Thr Met Asp Lys Ser Ser Ser Thr Ala Tyr
210 215 220
Met Glu Leu Leu Ser Leu Thr Ser Glu Asp Ser Ala Ile Tyr Phe Cys
225 230 235 240
Ala Arg Asp Tyr Arg Tyr Glu Gly Phe Asp Tyr Trp Gly Gln Gly Thr
245 250 255
Leu Val Thr Val Ser Ala Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr
260 265 270
Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala
275 280 285
Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe
290 295 300
Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val
305 310 315 320
Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys
325 330 335
Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr
340 345 350
Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu
355 360 365
Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro
370 375 380
Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly
385 390 395 400
Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro
405 410 415
Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr
420 425 430
Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly
435 440 445
Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln
450 455 460
Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln
465 470 475 480
Ala Leu Pro Pro Arg
485
<210> 30
<211> 241
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 30
Gln Ile Val Leu Thr Gln Ser Pro Ala Ile Met Ser Ala Ser Leu Gly
1 5 10 15
Glu Arg Val Thr Met Thr Cys Thr Ala Ser Ser Val Val Ile Ser Thr
20 25 30
Tyr Leu His Trp Tyr Gln Gln Lys Pro Gly Ser Ser Pro Lys Leu Trp
35 40 45
Ile Tyr Ser Thr Ser Asn Leu Ala Ser Gly Val Pro Val Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile Ser Ser Met Glu
65 70 75 80
Ala Glu Asp Ala Ala Thr Tyr Tyr Cys His Gln Tyr His Arg Ser Pro
85 90 95
Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Gln Leu Gln
115 120 125
Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Gly Ser Met Lys Ile Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr Thr Met Asn Trp Val
145 150 155 160
Lys Gln Ser His Gly Lys Asn Leu Glu Trp Ile Gly Leu Ile Asn Pro
165 170 175
Tyr Asn Gly Gly Ile Ser Tyr Asn Gln Lys Phe Lys Asp Lys Ala Thr
180 185 190
Leu Thr Met Asp Lys Ser Ser Ser Thr Ala Tyr Met Glu Leu Leu Ser
195 200 205
Leu Thr Ser Glu Asp Ser Ala Ile Tyr Phe Cys Ala Arg Asp Tyr Arg
210 215 220
Tyr Glu Gly Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
225 230 235 240
Ala
<210> 31
<211> 108
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 31
Gln Ile Val Leu Thr Gln Ser Pro Ala Ile Met Ser Ala Ser Leu Gly
1 5 10 15
Glu Arg Val Thr Met Thr Cys Thr Ala Ser Ser Val Val Ile Ser Thr
20 25 30
Tyr Leu His Trp Tyr Gln Gln Lys Pro Gly Ser Ser Pro Lys Leu Trp
35 40 45
Ile Tyr Ser Thr Ser Asn Leu Ala Ser Gly Val Pro Val Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile Ser Ser Met Glu
65 70 75 80
Ala Glu Asp Ala Ala Thr Tyr Tyr Cys His Gln Tyr His Arg Ser Pro
85 90 95
Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 32
<211> 118
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 32
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Gly
1 5 10 15
Ser Met Lys Ile Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr
20 25 30
Thr Met Asn Trp Val Lys Gln Ser His Gly Lys Asn Leu Glu Trp Ile
35 40 45
Gly Leu Ile Asn Pro Tyr Asn Gly Gly Ile Ser Tyr Asn Gln Lys Phe
50 55 60
Lys Asp Lys Ala Thr Leu Thr Met Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Leu Ser Leu Thr Ser Glu Asp Ser Ala Ile Tyr Phe Cys
85 90 95
Ala Arg Asp Tyr Arg Tyr Glu Gly Phe Asp Tyr Trp Gly Gln Gly Thr
100 105 110
Leu Val Thr Val Ser Ala
115
<210> 33
<211> 488
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 33
Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu
1 5 10 15
His Ala Ala Arg Pro Glu Asn Val Leu Thr Gln Ser Pro Ala Ile Met
20 25 30
Ser Ala Thr Leu Gly Glu Lys Val Thr Met Ser Cys Arg Ala Thr Ser
35 40 45
Asn Val Lys Tyr Met Tyr Trp Tyr Gln Gln Lys Ser Gly Ala Ser Pro
50 55 60
Lys Leu Trp Ile Tyr Tyr Thr Ser Asn Leu Ala Ser Gly Val Pro Ala
65 70 75 80
Arg Phe Ser Gly Ser Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile Ser
85 90 95
Ser Val Glu Ala Ala Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Phe Thr
100 105 110
Ser Ser Pro Ser Thr Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys Gly
115 120 125
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val
130 135 140
Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala Ser Val
145 150 155 160
Lys Ile Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr Phe Met
165 170 175
Asn Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile Gly Arg
180 185 190
Ile Asn Pro Tyr Asn Gly Asp Thr Phe Tyr Asn Gln Lys Phe Lys Gly
195 200 205
Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Asn Thr Ala His Met Glu
210 215 220
Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys Ala Arg
225 230 235 240
Val Leu Phe Leu Asp Phe Asp Asp Pro Tyr Leu Met Asp Tyr Trp Gly
245 250 255
Gln Gly Thr Ser Val Thr Val Ser Ser Thr Thr Thr Pro Ala Pro Arg
260 265 270
Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg
275 280 285
Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly
290 295 300
Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr
305 310 315 320
Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg
325 330 335
Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro
340 345 350
Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu
355 360 365
Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala
370 375 380
Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu
385 390 395 400
Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly
405 410 415
Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu
420 425 430
Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser
435 440 445
Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly
450 455 460
Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu
465 470 475 480
His Met Gln Ala Leu Pro Pro Arg
485
<210> 34
<211> 244
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 34
Glu Asn Val Leu Thr Gln Ser Pro Ala Ile Met Ser Ala Thr Leu Gly
1 5 10 15
Glu Lys Val Thr Met Ser Cys Arg Ala Thr Ser Asn Val Lys Tyr Met
20 25 30
Tyr Trp Tyr Gln Gln Lys Ser Gly Ala Ser Pro Lys Leu Trp Ile Tyr
35 40 45
Tyr Thr Ser Asn Leu Ala Ser Gly Val Pro Ala Arg Phe Ser Gly Ser
50 55 60
Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile Ser Ser Val Glu Ala Ala
65 70 75 80
Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Phe Thr Ser Ser Pro Ser Thr
85 90 95
Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys Gly Gly Gly Gly Ser Gly
100 105 110
Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Gln Leu Gln Gln Ser
115 120 125
Gly Pro Glu Leu Val Lys Pro Gly Ala Ser Val Lys Ile Ser Cys Lys
130 135 140
Ala Ser Gly Tyr Ser Phe Thr Gly Tyr Phe Met Asn Trp Val Lys Gln
145 150 155 160
Ser His Gly Lys Ser Leu Glu Trp Ile Gly Arg Ile Asn Pro Tyr Asn
165 170 175
Gly Asp Thr Phe Tyr Asn Gln Lys Phe Lys Gly Lys Ala Thr Leu Thr
180 185 190
Val Asp Lys Ser Ser Asn Thr Ala His Met Glu Leu Arg Ser Leu Thr
195 200 205
Ser Glu Asp Ser Ala Val Tyr Tyr Cys Ala Arg Val Leu Phe Leu Asp
210 215 220
Phe Asp Asp Pro Tyr Leu Met Asp Tyr Trp Gly Gln Gly Thr Ser Val
225 230 235 240
Thr Val Ser Ser
<210> 35
<211> 106
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 35
Asn Val Leu Thr Gln Ser Pro Ala Ile Met Ser Ala Thr Leu Gly Glu
1 5 10 15
Lys Val Thr Met Ser Cys Arg Ala Thr Ser Asn Val Lys Tyr Met Tyr
20 25 30
Trp Tyr Gln Gln Lys Ser Gly Ala Ser Pro Lys Leu Trp Ile Tyr Tyr
35 40 45
Thr Ser Asn Leu Ala Ser Gly Val Pro Ala Arg Phe Ser Gly Ser Gly
50 55 60
Ser Gly Thr Ser Tyr Ser Leu Thr Ile Ser Ser Val Glu Ala Ala Asp
65 70 75 80
Ala Ala Thr Tyr Tyr Cys Gln Gln Phe Thr Ser Ser Pro Ser Thr Phe
85 90 95
Gly Ala Gly Thr Lys Leu Glu Leu Lys Glu
100 105
<210> 36
<211> 123
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 36
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr
20 25 30
Phe Met Asn Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile
35 40 45
Gly Arg Ile Asn Pro Tyr Asn Gly Asp Thr Phe Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Asn Thr Ala His
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Val Leu Phe Leu Asp Phe Asp Asp Pro Tyr Leu Met Asp Tyr
100 105 110
Trp Gly Gln Gly Thr Ser Val Thr Val Ser Ser
115 120
<210> 37
<211> 485
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 37
Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu
1 5 10 15
His Ala Ala Arg Pro Asp Ile Gln Met Thr Gln Ser Pro Ala Ser Leu
20 25 30
Ser Ala Ser Val Gly Glu Thr Val Thr Ile Thr Cys Arg Ala Ser Glu
35 40 45
Asn Ile Asp Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Gln Gly Lys Ser
50 55 60
Pro Gln Leu Leu Val Tyr Ala Ser Thr Leu Leu Val Asp Gly Val Pro
65 70 75 80
Ser Arg Phe Ser Gly Ser Arg Ser Gly Thr Gln Phe Ser Leu Lys Ile
85 90 95
Asn Ser Leu Gln Ser Glu Asp Val Ala Arg Tyr Tyr Cys Gln His Tyr
100 105 110
Tyr Ser Ile Pro Tyr Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
115 120 125
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu
130 135 140
Val Lys Leu Val Glu Ser Gly Gly Gly Leu Val Lys Pro Gly Gly Ser
145 150 155 160
Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Ser Tyr Thr
165 170 175
Met Ser Trp Val Arg Gln Thr Pro Ala Lys Arg Leu Glu Trp Val Val
180 185 190
Thr Ile Ser Ser Gly Gly Gly Arg Thr Tyr Tyr Pro Asp Ser Val Lys
195 200 205
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Arg Asn Thr Leu Tyr Leu
210 215 220
Gln Met Ser Ser Leu Arg Ser Glu Asp Thr Ala Met Tyr Tyr Cys Ile
225 230 235 240
Arg Gly Asp Tyr Arg Tyr Asp Gly Phe Ala Tyr Trp Gly Gln Gly Thr
245 250 255
Leu Val Thr Val Ser Thr Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr
260 265 270
Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala
275 280 285
Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe
290 295 300
Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val
305 310 315 320
Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys
325 330 335
Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr
340 345 350
Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu
355 360 365
Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro
370 375 380
Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly
385 390 395 400
Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro
405 410 415
Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr
420 425 430
Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly
435 440 445
Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln
450 455 460
Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln
465 470 475 480
Ala Leu Pro Pro Arg
485
<210> 38
<211> 241
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 38
Asp Ile Gln Met Thr Gln Ser Pro Ala Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Glu Thr Val Thr Ile Thr Cys Arg Ala Ser Glu Asn Ile Asp Ser Tyr
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Gln Gly Lys Ser Pro Gln Leu Leu Val
35 40 45
Tyr Ala Ser Thr Leu Leu Val Asp Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Arg Ser Gly Thr Gln Phe Ser Leu Lys Ile Asn Ser Leu Gln Ser
65 70 75 80
Glu Asp Val Ala Arg Tyr Tyr Cys Gln His Tyr Tyr Ser Ile Pro Tyr
85 90 95
Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser
100 105 110
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Lys Leu Val Glu
115 120 125
Ser Gly Gly Gly Leu Val Lys Pro Gly Gly Ser Leu Lys Leu Ser Cys
130 135 140
Ala Ala Ser Gly Phe Thr Phe Asn Ser Tyr Thr Met Ser Trp Val Arg
145 150 155 160
Gln Thr Pro Ala Lys Arg Leu Glu Trp Val Val Thr Ile Ser Ser Gly
165 170 175
Gly Gly Arg Thr Tyr Tyr Pro Asp Ser Val Lys Gly Arg Phe Thr Ile
180 185 190
Ser Arg Asp Asn Ala Arg Asn Thr Leu Tyr Leu Gln Met Ser Ser Leu
195 200 205
Arg Ser Glu Asp Thr Ala Met Tyr Tyr Cys Ile Arg Gly Asp Tyr Arg
210 215 220
Tyr Asp Gly Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
225 230 235 240
Thr
<210> 39
<211> 107
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 39
Asp Ile Gln Met Thr Gln Ser Pro Ala Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Glu Thr Val Thr Ile Thr Cys Arg Ala Ser Glu Asn Ile Asp Ser Tyr
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Gln Gly Lys Ser Pro Gln Leu Leu Val
35 40 45
Tyr Ala Ser Thr Leu Leu Val Asp Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Arg Ser Gly Thr Gln Phe Ser Leu Lys Ile Asn Ser Leu Gln Ser
65 70 75 80
Glu Asp Val Ala Arg Tyr Tyr Cys Gln His Tyr Tyr Ser Ile Pro Tyr
85 90 95
Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 40
<211> 119
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 40
Glu Val Lys Leu Val Glu Ser Gly Gly Gly Leu Val Lys Pro Gly Gly
1 5 10 15
Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Ser Tyr
20 25 30
Thr Met Ser Trp Val Arg Gln Thr Pro Ala Lys Arg Leu Glu Trp Val
35 40 45
Val Thr Ile Ser Ser Gly Gly Gly Arg Thr Tyr Tyr Pro Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Arg Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Ser Ser Leu Arg Ser Glu Asp Thr Ala Met Tyr Tyr Cys
85 90 95
Ile Arg Gly Asp Tyr Arg Tyr Asp Gly Phe Ala Tyr Trp Gly Gln Gly
100 105 110
Thr Leu Val Thr Val Ser Thr
115
<210> 41
<211> 488
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 41
Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu
1 5 10 15
His Ala Ala Arg Pro Glu Asn Val Leu Thr Gln Ser Pro Ala Ile Met
20 25 30
Ser Ala Thr Leu Gly Glu Lys Val Thr Met Ser Cys Arg Ala Thr Ser
35 40 45
Asn Val Lys Tyr Met Tyr Trp Tyr Gln Gln Lys Ser Gly Ala Ser Pro
50 55 60
Lys Leu Trp Ile Tyr Tyr Thr Ser Asn Leu Ala Ser Gly Val Pro Ala
65 70 75 80
Arg Phe Ser Gly Ser Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile Ser
85 90 95
Ser Val Glu Ala Ala Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Phe Thr
100 105 110
Ser Ser Pro Ser Thr Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys Gly
115 120 125
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val
130 135 140
Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala Ser Val
145 150 155 160
Lys Ile Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr Phe Met
165 170 175
Asn Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile Gly Arg
180 185 190
Ile Asn Pro Tyr Asn Gly Asp Thr Phe Tyr Asn Gln Lys Phe Lys Gly
195 200 205
Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser Thr Ala His Met Glu
210 215 220
Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys Ala Arg
225 230 235 240
Val Leu Phe Leu Asp Phe Asp Asp Pro Tyr Leu Met Asp Tyr Trp Gly
245 250 255
Gln Gly Thr Ser Val Thr Val Ser Ser Thr Thr Thr Pro Ala Pro Arg
260 265 270
Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg
275 280 285
Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly
290 295 300
Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr
305 310 315 320
Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg
325 330 335
Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro
340 345 350
Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu
355 360 365
Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala
370 375 380
Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu
385 390 395 400
Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly
405 410 415
Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu
420 425 430
Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser
435 440 445
Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly
450 455 460
Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu
465 470 475 480
His Met Gln Ala Leu Pro Pro Arg
485
<210> 42
<211> 244
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 42
Glu Asn Val Leu Thr Gln Ser Pro Ala Ile Met Ser Ala Thr Leu Gly
1 5 10 15
Glu Lys Val Thr Met Ser Cys Arg Ala Thr Ser Asn Val Lys Tyr Met
20 25 30
Tyr Trp Tyr Gln Gln Lys Ser Gly Ala Ser Pro Lys Leu Trp Ile Tyr
35 40 45
Tyr Thr Ser Asn Leu Ala Ser Gly Val Pro Ala Arg Phe Ser Gly Ser
50 55 60
Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile Ser Ser Val Glu Ala Ala
65 70 75 80
Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Phe Thr Ser Ser Pro Ser Thr
85 90 95
Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys Gly Gly Gly Gly Ser Gly
100 105 110
Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Gln Leu Gln Gln Ser
115 120 125
Gly Pro Glu Leu Val Lys Pro Gly Ala Ser Val Lys Ile Ser Cys Lys
130 135 140
Ala Ser Gly Tyr Ser Phe Thr Gly Tyr Phe Met Asn Trp Val Lys Gln
145 150 155 160
Ser His Gly Lys Ser Leu Glu Trp Ile Gly Arg Ile Asn Pro Tyr Asn
165 170 175
Gly Asp Thr Phe Tyr Asn Gln Lys Phe Lys Gly Lys Ala Thr Leu Thr
180 185 190
Val Asp Lys Ser Ser Ser Thr Ala His Met Glu Leu Arg Ser Leu Thr
195 200 205
Ser Glu Asp Ser Ala Val Tyr Tyr Cys Ala Arg Val Leu Phe Leu Asp
210 215 220
Phe Asp Asp Pro Tyr Leu Met Asp Tyr Trp Gly Gln Gly Thr Ser Val
225 230 235 240
Thr Val Ser Ser
<210> 43
<211> 106
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 43
Glu Asn Val Leu Thr Gln Ser Pro Ala Ile Met Ser Ala Thr Leu Gly
1 5 10 15
Glu Lys Val Thr Met Ser Cys Arg Ala Thr Ser Asn Val Lys Tyr Met
20 25 30
Tyr Trp Tyr Gln Gln Lys Ser Gly Ala Ser Pro Lys Leu Trp Ile Tyr
35 40 45
Tyr Thr Ser Asn Leu Ala Ser Gly Val Pro Ala Arg Phe Ser Gly Ser
50 55 60
Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile Ser Ser Val Glu Ala Ala
65 70 75 80
Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Phe Thr Ser Ser Pro Ser Thr
85 90 95
Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys
100 105
<210> 44
<211> 123
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 44
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr
20 25 30
Phe Met Asn Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile
35 40 45
Gly Arg Ile Asn Pro Tyr Asn Gly Asp Thr Phe Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser Thr Ala His
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Val Leu Phe Leu Asp Phe Asp Asp Pro Tyr Leu Met Asp Tyr
100 105 110
Trp Gly Gln Gly Thr Ser Val Thr Val Ser Ser
115 120
<210> 45
<211> 482
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 45
Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu
1 5 10 15
His Ala Ala Arg Pro Ser Ser Glu Leu Thr Gln Asp Pro Ala Val Ser
20 25 30
Val Ala Leu Gly Gln Thr Val Arg Ile Thr Cys Arg Gly Asp Ser Leu
35 40 45
Arg Lys Tyr Tyr Ala Ser Trp Tyr Gln Gln Lys Pro Arg Gln Ala Pro
50 55 60
Gln Leu Val Ile Tyr His Lys Asn Asn Arg Ala Ser Gly Ile Pro Asp
65 70 75 80
Arg Phe Ser Gly Ser Ile Ser Gly Asn Thr Ala Ser Leu Thr Ile Thr
85 90 95
Gly Ala Gln Ala Glu Asp Glu Ala Ala Tyr Phe Cys Asn Ser Arg Asp
100 105 110
Thr Ser Gly Asn Tyr Leu Val Phe Gly Gly Gly Thr Lys Val Thr Val
115 120 125
Leu Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
130 135 140
Ser Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser
145 150 155 160
Glu Thr Leu Ser Leu Thr Cys Ala Val Ser Gly Ala Ser Ile Ser Asn
165 170 175
Trp Trp Ser Trp Val Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile
180 185 190
Gly Glu Val His His Ser Gly Val Thr Thr Tyr Lys Pro Ser Leu Lys
195 200 205
Ser Arg Val Thr Ile Ser Val Asp Asn Ser Lys Asn Gln Leu Ser Leu
210 215 220
Lys Leu Thr Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala
225 230 235 240
Arg Glu Phe Ala Asp Asp Ala Phe Asp Ile Trp Gly Arg Gly Thr Met
245 250 255
Val Thr Val Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro
260 265 270
Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro
275 280 285
Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp
290 295 300
Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu
305 310 315 320
Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu
325 330 335
Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu
340 345 350
Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys
355 360 365
Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Lys
370 375 380
Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu
385 390 395 400
Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly
405 410 415
Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu
420 425 430
Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly
435 440 445
Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser
450 455 460
Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro
465 470 475 480
Pro Arg
<210> 46
<211> 238
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 46
Ser Ser Glu Leu Thr Gln Asp Pro Ala Val Ser Val Ala Leu Gly Gln
1 5 10 15
Thr Val Arg Ile Thr Cys Arg Gly Asp Ser Leu Arg Lys Tyr Tyr Ala
20 25 30
Ser Trp Tyr Gln Gln Lys Pro Arg Gln Ala Pro Gln Leu Val Ile Tyr
35 40 45
His Lys Asn Asn Arg Ala Ser Gly Ile Pro Asp Arg Phe Ser Gly Ser
50 55 60
Ile Ser Gly Asn Thr Ala Ser Leu Thr Ile Thr Gly Ala Gln Ala Glu
65 70 75 80
Asp Glu Ala Ala Tyr Phe Cys Asn Ser Arg Asp Thr Ser Gly Asn Tyr
85 90 95
Leu Val Phe Gly Gly Gly Thr Lys Val Thr Val Leu Gly Gly Gly Gly
100 105 110
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Leu Gln Leu
115 120 125
Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu
130 135 140
Thr Cys Ala Val Ser Gly Ala Ser Ile Ser Asn Trp Trp Ser Trp Val
145 150 155 160
Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Glu Val His His
165 170 175
Ser Gly Val Thr Thr Tyr Lys Pro Ser Leu Lys Ser Arg Val Thr Ile
180 185 190
Ser Val Asp Asn Ser Lys Asn Gln Leu Ser Leu Lys Leu Thr Ser Val
195 200 205
Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg Glu Phe Ala Asp
210 215 220
Asp Ala Phe Asp Ile Trp Gly Arg Gly Thr Met Val Thr Val
225 230 235
<210> 47
<211> 109
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 47
Ser Ser Glu Leu Thr Gln Asp Pro Ala Val Ser Val Ala Leu Gly Gln
1 5 10 15
Thr Val Arg Ile Thr Cys Arg Gly Asp Ser Leu Arg Lys Tyr Tyr Ala
20 25 30
Ser Trp Tyr Gln Gln Lys Pro Arg Gln Ala Pro Gln Leu Val Ile Tyr
35 40 45
His Lys Asn Asn Arg Ala Ser Gly Ile Pro Asp Arg Phe Ser Gly Ser
50 55 60
Ile Ser Gly Asn Thr Ala Ser Leu Thr Ile Thr Gly Ala Gln Ala Glu
65 70 75 80
Asp Glu Ala Ala Tyr Phe Cys Asn Ser Arg Asp Thr Ser Gly Asn Tyr
85 90 95
Leu Val Phe Gly Gly Gly Thr Lys Val Thr Val Leu Gly
100 105
<210> 48
<211> 114
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 48
Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Ala Val Ser Gly Ala Ser Ile Ser Asn Trp
20 25 30
Trp Ser Trp Val Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly
35 40 45
Glu Val His His Ser Gly Val Thr Thr Tyr Lys Pro Ser Leu Lys Ser
50 55 60
Arg Val Thr Ile Ser Val Asp Asn Ser Lys Asn Gln Leu Ser Leu Lys
65 70 75 80
Leu Thr Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg
85 90 95
Glu Phe Ala Asp Asp Ala Phe Asp Ile Trp Gly Arg Gly Thr Met Val
100 105 110
Thr Val
<210> 49
<211> 250
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 49
Asp Ile Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Pro Gly
1 5 10 15
Glu Pro Ala Ser Ile Ser Cys Arg Ser Thr Lys Ser Leu Leu His Ser
20 25 30
Asn Gly Asn Thr Tyr Leu Tyr Trp Tyr Leu Gln Lys Pro Gly Gln Ser
35 40 45
Pro Gln Leu Leu Ile Tyr Arg Met Ser Asn Leu Ala Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln His
85 90 95
Leu Glu Tyr Pro Phe Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105 110
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu
115 120 125
Ile Gln Leu Gln Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser Ser
130 135 140
Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr Asp
145 150 155 160
Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly
165 170 175
Thr Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe Lys
180 185 190
Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr Ala Tyr Met
195 200 205
Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Thr
210 215 220
Ser Phe Tyr Tyr Thr Tyr Ser Asn Tyr Asp Val Gly Phe Ala Tyr Trp
225 230 235 240
Gly Gln Gly Thr Leu Val Thr Val Ser Ser
245 250
<210> 50
<211> 250
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 50
Asp Ile Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Pro Gly
1 5 10 15
Glu Pro Ala Ser Ile Ser Cys Arg Ser Thr Lys Ser Leu Leu His Ser
20 25 30
Asn Gly Asn Thr Tyr Leu Tyr Trp Tyr Leu Gln Lys Pro Gly Gln Ser
35 40 45
Pro Gln Leu Leu Ile Tyr Arg Met Ser Asn Leu Ala Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln His
85 90 95
Leu Glu Tyr Pro Phe Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105 110
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu
115 120 125
Ile Gln Leu Gln Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser Ser
130 135 140
Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr Asp
145 150 155 160
Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile Gly
165 170 175
Thr Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe Lys
180 185 190
Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Ser Thr Ala Tyr Met
195 200 205
Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Thr
210 215 220
Ser Phe Tyr Tyr Thr Tyr Ser Asn Tyr Asp Val Gly Phe Ala Tyr Trp
225 230 235 240
Gly Gln Gly Thr Leu Val Thr Val Ser Ser
245 250
<210> 51
<211> 250
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 51
Asp Ile Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Pro Gly
1 5 10 15
Glu Pro Ala Ser Ile Ser Cys Arg Ser Thr Lys Ser Leu Leu His Ser
20 25 30
Asn Gly Asn Thr Tyr Leu Tyr Trp Tyr Leu Gln Lys Pro Gly Gln Ser
35 40 45
Pro Gln Leu Leu Ile Tyr Arg Met Ser Asn Leu Ala Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln His
85 90 95
Leu Glu Tyr Pro Phe Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105 110
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu
115 120 125
Ile Gln Leu Gln Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser Ser
130 135 140
Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr Asp
145 150 155 160
Met His Trp Val Lys Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile Gly
165 170 175
Thr Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe Lys
180 185 190
Gly Lys Ala Thr Leu Thr Ala Asp Arg Ser Thr Ser Thr Ala Tyr Met
195 200 205
Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Thr
210 215 220
Ser Phe Tyr Tyr Thr Tyr Ser Asn Tyr Asp Val Gly Phe Ala Tyr Trp
225 230 235 240
Gly Gln Gly Thr Leu Val Thr Val Ser Ser
245 250
<210> 52
<211> 250
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 52
Asp Ile Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Pro Gly
1 5 10 15
Glu Pro Ala Ser Ile Ser Cys Arg Ser Thr Lys Ser Leu Leu His Ser
20 25 30
Asn Gly Asn Thr Tyr Leu Tyr Trp Tyr Leu Gln Lys Pro Gly Gln Ser
35 40 45
Pro Gln Leu Leu Ile Tyr Arg Met Ser Asn Leu Ala Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln His
85 90 95
Leu Glu Tyr Pro Phe Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105 110
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu
115 120 125
Ile Gln Leu Gln Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser Ser
130 135 140
Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr Asp
145 150 155 160
Met His Trp Val Lys Gln Ala Pro Gly His Gly Leu Glu Trp Ile Gly
165 170 175
Thr Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe Lys
180 185 190
Gly Lys Ala Thr Leu Thr Ala Asp Arg Ser Thr Ser Thr Ala Tyr Met
195 200 205
Glu Leu Ser Ser Leu Thr Ser Glu Asp Thr Ala Val Tyr Tyr Cys Thr
210 215 220
Ser Phe Tyr Tyr Thr Tyr Ser Asn Tyr Asp Val Gly Phe Ala Tyr Trp
225 230 235 240
Gly Gln Gly Thr Leu Val Thr Val Ser Ser
245 250
<210> 53
<211> 250
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 53
Asp Ile Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Pro Gly
1 5 10 15
Glu Pro Ala Ser Ile Ser Cys Arg Ser Thr Lys Ser Leu Leu His Ser
20 25 30
Asn Gly Asn Thr Tyr Leu Tyr Trp Phe Leu Gln Lys Pro Gly Gln Ser
35 40 45
Pro Gln Leu Leu Ile Tyr Arg Met Ser Asn Leu Ala Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln His
85 90 95
Leu Glu Tyr Pro Phe Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105 110
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu
115 120 125
Ile Gln Leu Gln Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser Ser
130 135 140
Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr Asp
145 150 155 160
Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly
165 170 175
Thr Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe Lys
180 185 190
Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr Ala Tyr Met
195 200 205
Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Thr
210 215 220
Ser Phe Tyr Tyr Thr Tyr Ser Asn Tyr Asp Val Gly Phe Ala Tyr Trp
225 230 235 240
Gly Gln Gly Thr Leu Val Thr Val Ser Ser
245 250
<210> 54
<211> 250
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 54
Asp Ile Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Pro Gly
1 5 10 15
Glu Pro Ala Ser Ile Ser Cys Arg Ser Thr Lys Ser Leu Leu His Ser
20 25 30
Asn Gly Asn Thr Tyr Leu Tyr Trp Phe Leu Gln Lys Pro Gly Gln Ser
35 40 45
Pro Gln Leu Leu Ile Tyr Arg Met Ser Asn Leu Ala Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln His
85 90 95
Leu Glu Tyr Pro Phe Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105 110
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu
115 120 125
Ile Gln Leu Gln Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser Ser
130 135 140
Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr Asp
145 150 155 160
Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile Gly
165 170 175
Thr Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe Lys
180 185 190
Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Ser Thr Ala Tyr Met
195 200 205
Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Thr
210 215 220
Ser Phe Tyr Tyr Thr Tyr Ser Asn Tyr Asp Val Gly Phe Ala Tyr Trp
225 230 235 240
Gly Gln Gly Thr Leu Val Thr Val Ser Ser
245 250
<210> 55
<211> 250
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 55
Asp Ile Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Pro Gly
1 5 10 15
Glu Pro Ala Ser Ile Ser Cys Arg Ser Thr Lys Ser Leu Leu His Ser
20 25 30
Asn Gly Asn Thr Tyr Leu Tyr Trp Phe Leu Gln Lys Pro Gly Gln Ser
35 40 45
Pro Gln Leu Leu Ile Tyr Arg Met Ser Asn Leu Ala Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln His
85 90 95
Leu Glu Tyr Pro Phe Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105 110
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu
115 120 125
Ile Gln Leu Gln Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser Ser
130 135 140
Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr Asp
145 150 155 160
Met His Trp Val Lys Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile Gly
165 170 175
Thr Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe Lys
180 185 190
Gly Lys Ala Thr Leu Thr Ala Asp Arg Ser Thr Ser Thr Ala Tyr Met
195 200 205
Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Thr
210 215 220
Ser Phe Tyr Tyr Thr Tyr Ser Asn Tyr Asp Val Gly Phe Ala Tyr Trp
225 230 235 240
Gly Gln Gly Thr Leu Val Thr Val Ser Ser
245 250
<210> 56
<211> 250
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 56
Asp Ile Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Pro Gly
1 5 10 15
Glu Pro Ala Ser Ile Ser Cys Arg Ser Thr Lys Ser Leu Leu His Ser
20 25 30
Asn Gly Asn Thr Tyr Leu Tyr Trp Phe Leu Gln Lys Pro Gly Gln Ser
35 40 45
Pro Gln Leu Leu Ile Tyr Arg Met Ser Asn Leu Ala Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln His
85 90 95
Leu Glu Tyr Pro Phe Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105 110
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu
115 120 125
Ile Gln Leu Gln Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser Ser
130 135 140
Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr Asp
145 150 155 160
Met His Trp Val Lys Gln Ala Pro Gly His Gly Leu Glu Trp Ile Gly
165 170 175
Thr Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe Lys
180 185 190
Gly Lys Ala Thr Leu Thr Ala Asp Arg Ser Thr Ser Thr Ala Tyr Met
195 200 205
Glu Leu Ser Ser Leu Thr Ser Glu Asp Thr Ala Val Tyr Tyr Cys Thr
210 215 220
Ser Phe Tyr Tyr Thr Tyr Ser Asn Tyr Asp Val Gly Phe Ala Tyr Trp
225 230 235 240
Gly Gln Gly Thr Leu Val Thr Val Ser Ser
245 250
<210> 57
<211> 112
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 57
Asp Ile Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Pro Gly
1 5 10 15
Glu Pro Ala Ser Ile Ser Cys Arg Ser Thr Lys Ser Leu Leu His Ser
20 25 30
Asn Gly Asn Thr Tyr Leu Tyr Trp Tyr Leu Gln Lys Pro Gly Gln Ser
35 40 45
Pro Gln Leu Leu Ile Tyr Arg Met Ser Asn Leu Ala Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln His
85 90 95
Leu Glu Tyr Pro Phe Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105 110
<210> 58
<211> 112
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 58
Asp Ile Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Pro Gly
1 5 10 15
Glu Pro Ala Ser Ile Ser Cys Arg Ser Thr Lys Ser Leu Leu His Ser
20 25 30
Asn Gly Asn Thr Tyr Leu Tyr Trp Phe Leu Gln Lys Pro Gly Gln Ser
35 40 45
Pro Gln Leu Leu Ile Tyr Arg Met Ser Asn Leu Ala Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln His
85 90 95
Leu Glu Tyr Pro Phe Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105 110
<210> 59
<211> 123
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 59
Glu Ile Gln Leu Gln Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Asp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Thr Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Ser Phe Tyr Tyr Thr Tyr Ser Asn Tyr Asp Val Gly Phe Ala Tyr
100 105 110
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 60
<211> 123
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 60
Glu Ile Gln Leu Gln Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Asp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Thr Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Ser Phe Tyr Tyr Thr Tyr Ser Asn Tyr Asp Val Gly Phe Ala Tyr
100 105 110
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 61
<211> 123
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 61
Glu Ile Gln Leu Gln Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Asp Met His Trp Val Lys Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Thr Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Ala Asp Arg Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Ser Phe Tyr Tyr Thr Tyr Ser Asn Tyr Asp Val Gly Phe Ala Tyr
100 105 110
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 62
<211> 123
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 62
Glu Ile Gln Leu Gln Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Asp Met His Trp Val Lys Gln Ala Pro Gly His Gly Leu Glu Trp Ile
35 40 45
Gly Thr Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Ala Asp Arg Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Thr Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Ser Phe Tyr Tyr Thr Tyr Ser Asn Tyr Asp Val Gly Phe Ala Tyr
100 105 110
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 63
<211> 482
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 63
Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu
1 5 10 15
His Ala Ala Arg Pro Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu
20 25 30
Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Asp
35 40 45
Leu Ile His Asn Trp Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala
50 55 60
Pro Lys Leu Leu Ile Tyr Gly Ala Thr Ser Leu Glu Thr Gly Val Pro
65 70 75 80
Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile
85 90 95
Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr
100 105 110
Trp Thr Thr Pro Phe Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
115 120 125
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu
130 135 140
Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser
145 150 155 160
Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser Ile Thr Asn Asp Tyr
165 170 175
Ala Trp Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
180 185 190
Gly Tyr Ile Ser Tyr Ser Gly Tyr Thr Thr Tyr Asn Pro Ser Leu Lys
195 200 205
Ser Arg Phe Thr Ile Ser Arg Asp Thr Ser Lys Asn Thr Leu Tyr Leu
210 215 220
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala
225 230 235 240
Arg Trp Thr Ser Gly Leu Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr
245 250 255
Val Ser Ser Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro
260 265 270
Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro
275 280 285
Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp
290 295 300
Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu
305 310 315 320
Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu
325 330 335
Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu
340 345 350
Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys
355 360 365
Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Lys
370 375 380
Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu
385 390 395 400
Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly
405 410 415
Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu
420 425 430
Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly
435 440 445
Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser
450 455 460
Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro
465 470 475 480
Pro Arg
<210> 64
<211> 238
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 64
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Asp Leu Ile His Asn Trp
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Gly Ala Thr Ser Leu Glu Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Trp Thr Thr Pro Phe
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Gly Gly Gly Gly Ser
100 105 110
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Gln Leu Val Glu
115 120 125
Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys
130 135 140
Ala Ala Ser Gly Tyr Ser Ile Thr Asn Asp Tyr Ala Trp Asn Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Gly Tyr Ile Ser Tyr
165 170 175
Ser Gly Tyr Thr Thr Tyr Asn Pro Ser Leu Lys Ser Arg Phe Thr Ile
180 185 190
Ser Arg Asp Thr Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu
195 200 205
Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Trp Thr Ser Gly
210 215 220
Leu Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
225 230 235
<210> 65
<211> 107
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 65
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Asp Leu Ile His Asn Trp
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Gly Ala Thr Ser Leu Glu Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Trp Thr Thr Pro Phe
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 66
<211> 116
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 66
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser Ile Thr Asn Asp
20 25 30
Tyr Ala Trp Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
35 40 45
Val Gly Tyr Ile Ser Tyr Ser Gly Tyr Thr Thr Tyr Asn Pro Ser Leu
50 55 60
Lys Ser Arg Phe Thr Ile Ser Arg Asp Thr Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Trp Thr Ser Gly Leu Asp Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser
115
<210> 67
<211> 482
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 67
Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu
1 5 10 15
His Ala Ala Arg Pro Asp Ile Gln Met Thr Gln Ser Ser Ser Phe Leu
20 25 30
Ser Val Ser Leu Gly Gly Arg Val Thr Ile Thr Cys Lys Ala Ser Asp
35 40 45
Leu Ile His Asn Trp Leu Ala Trp Tyr Gln Gln Lys Pro Gly Asn Ala
50 55 60
Pro Arg Leu Leu Ile Ser Gly Ala Thr Ser Leu Glu Thr Gly Val Pro
65 70 75 80
Ser Arg Phe Ser Gly Ser Gly Ser Gly Asn Asp Tyr Thr Leu Ser Ile
85 90 95
Ala Ser Leu Gln Thr Glu Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Tyr
100 105 110
Trp Thr Thr Pro Phe Thr Phe Gly Ser Gly Thr Lys Val Glu Ile Lys
115 120 125
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp
130 135 140
Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Asn Pro Ser Gln Ser
145 150 155 160
Leu Ser Leu Thr Cys Thr Val Thr Gly Tyr Ser Ile Thr Asn Asp Tyr
165 170 175
Ala Trp Asn Trp Ile Arg Gln Phe Pro Gly Asn Lys Leu Glu Trp Met
180 185 190
Gly Tyr Ile Asn Tyr Ser Gly Tyr Thr Thr Tyr Asn Pro Ser Leu Lys
195 200 205
Ser Arg Ile Ser Ile Thr Arg Asp Thr Ser Lys Asn Gln Phe Phe Leu
210 215 220
His Leu Asn Ser Val Thr Thr Glu Asp Thr Ala Thr Tyr Tyr Cys Ala
225 230 235 240
Arg Trp Asp Gly Gly Leu Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr
245 250 255
Val Ser Ala Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro
260 265 270
Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro
275 280 285
Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp
290 295 300
Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu
305 310 315 320
Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu
325 330 335
Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu
340 345 350
Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys
355 360 365
Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Lys
370 375 380
Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu
385 390 395 400
Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly
405 410 415
Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu
420 425 430
Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly
435 440 445
Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser
450 455 460
Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro
465 470 475 480
Pro Arg
<210> 68
<211> 238
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 68
Asp Ile Gln Met Thr Gln Ser Ser Ser Phe Leu Ser Val Ser Leu Gly
1 5 10 15
Gly Arg Val Thr Ile Thr Cys Lys Ala Ser Asp Leu Ile His Asn Trp
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Asn Ala Pro Arg Leu Leu Ile
35 40 45
Ser Gly Ala Thr Ser Leu Glu Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Asn Asp Tyr Thr Leu Ser Ile Ala Ser Leu Gln Thr
65 70 75 80
Glu Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Tyr Trp Thr Thr Pro Phe
85 90 95
Thr Phe Gly Ser Gly Thr Lys Val Glu Ile Lys Gly Gly Gly Gly Ser
100 105 110
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Val Gln Leu Gln Glu
115 120 125
Ser Gly Pro Gly Leu Val Asn Pro Ser Gln Ser Leu Ser Leu Thr Cys
130 135 140
Thr Val Thr Gly Tyr Ser Ile Thr Asn Asp Tyr Ala Trp Asn Trp Ile
145 150 155 160
Arg Gln Phe Pro Gly Asn Lys Leu Glu Trp Met Gly Tyr Ile Asn Tyr
165 170 175
Ser Gly Tyr Thr Thr Tyr Asn Pro Ser Leu Lys Ser Arg Ile Ser Ile
180 185 190
Thr Arg Asp Thr Ser Lys Asn Gln Phe Phe Leu His Leu Asn Ser Val
195 200 205
Thr Thr Glu Asp Thr Ala Thr Tyr Tyr Cys Ala Arg Trp Asp Gly Gly
210 215 220
Leu Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala
225 230 235
<210> 69
<211> 107
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 69
Asp Ile Gln Met Thr Gln Ser Ser Ser Phe Leu Ser Val Ser Leu Gly
1 5 10 15
Gly Arg Val Thr Ile Thr Cys Lys Ala Ser Asp Leu Ile His Asn Trp
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Asn Ala Pro Arg Leu Leu Ile
35 40 45
Ser Gly Ala Thr Ser Leu Glu Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Asn Asp Tyr Thr Leu Ser Ile Ala Ser Leu Gln Thr
65 70 75 80
Glu Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Tyr Trp Thr Thr Pro Phe
85 90 95
Thr Phe Gly Ser Gly Thr Lys Val Glu Ile Lys
100 105
<210> 70
<211> 116
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 70
Asp Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Asn Pro Ser Gln
1 5 10 15
Ser Leu Ser Leu Thr Cys Thr Val Thr Gly Tyr Ser Ile Thr Asn Asp
20 25 30
Tyr Ala Trp Asn Trp Ile Arg Gln Phe Pro Gly Asn Lys Leu Glu Trp
35 40 45
Met Gly Tyr Ile Asn Tyr Ser Gly Tyr Thr Thr Tyr Asn Pro Ser Leu
50 55 60
Lys Ser Arg Ile Ser Ile Thr Arg Asp Thr Ser Lys Asn Gln Phe Phe
65 70 75 80
Leu His Leu Asn Ser Val Thr Thr Glu Asp Thr Ala Thr Tyr Tyr Cys
85 90 95
Ala Arg Trp Asp Gly Gly Leu Thr Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ala
115
<210> 71
<211> 298
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 71
Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu
1 5 10 15
His Ala Ala Arg Pro Gly Thr Ser Leu Ser Pro Pro Pro Glu Ser Ser
20 25 30
Gly Ser Pro Gln Gln Pro Gly Leu Ser Ala Pro His Ser Arg Gln Ile
35 40 45
Pro Ala Pro Gln Gly Ala Val Leu Val Gln Arg Glu Lys Asp Leu Pro
50 55 60
Asn Tyr Asn Trp Asn Ser Phe Gly Leu Arg Phe Thr Thr Thr Pro Ala
65 70 75 80
Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser
85 90 95
Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr
100 105 110
Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala
115 120 125
Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys
130 135 140
Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met
145 150 155 160
Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe
165 170 175
Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg
180 185 190
Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn
195 200 205
Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg
210 215 220
Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro
225 230 235 240
Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala
245 250 255
Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His
260 265 270
Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp
275 280 285
Ala Leu His Met Gln Ala Leu Pro Pro Arg
290 295
<210> 72
<211> 54
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 72
Gly Thr Ser Leu Ser Pro Pro Pro Glu Ser Ser Gly Ser Pro Gln Gln
1 5 10 15
Pro Gly Leu Ser Ala Pro His Ser Arg Gln Ile Pro Ala Pro Gln Gly
20 25 30
Ala Val Leu Val Gln Arg Glu Lys Asp Leu Pro Asn Tyr Asn Trp Asn
35 40 45
Ser Phe Gly Leu Arg Phe
50
<210> 73
<211> 330
<212> DNA
<213> 人工序列（Artificial Sequence）
<400> 73
cagagcgtgc tgacacaacc cgccagcgtg agcggcagcc ccggccaatc cgtgacaatc 60
agctgcaccg gaaccagctc cgatgtgggc ggctacaact atgtcagctg gtaccagcag 120
caccccggca agccccctaa gctcatgatc tacgaggtca gcaagagacc ctccggagtg 180
cccgacagat tctccggctc caaatccggc aacaccgctt ccctcaccat cagcggactc 240
caagccgaag atgaggccga ctactactgc tccagccaca ccagcagcaa cacactgatc 300
tttggcggcg gcaccaaagt gacagtgctg 330
<210> 74
<211> 354
<212> DNA
<213> 人工序列（Artificial Sequence）
<400> 74
gaagtgcagc tggtgcaatc cggcgctgag gtgaagaagc ccggcgaatc tctgaagatt 60
agctgcaaag gctccggcta caccttcaca aactactgga tcggctgggt gagacagatg 120
cccggcaagg gactggagtg gatgggaaga atctacccca gcgactccta caccaactac 180
tccccctcct tccaaggcca agtgaccatt agcgccgaca agagcatctc caccgcctat 240
ctgcagtggt ccagcctcaa ggccagcgat acagccatgt actactgcgc cagagacctc 300
gagcctaccc atcattacag ctggggccaa ggcacactcg tgacagtgag ctcc 354
<210> 75
<211> 330
<212> DNA
<213> 人工序列（Artificial Sequence）
<400> 75
ctccccgtgc tgacacagcc tccttccgcc tccggaacac ccggccagag agtgaccatc 60
agctgcagcg gctccagctc caacatcggc agcaacgccg tggactggta tcagcaactg 120
cccggcacag ctcccaagct gctgatctac accaacaaca gaaggcccag cggcgtgccc 180
gatagattca gcggcagcaa atccggcaca agcggctctc tggccatttc cggactgcag 240
ttcgaggacg aggctgacta ctactgcgct gcttgggatg actctctgtc cggcgtgatc 300
tttggcggag gcaccaaggt cacagtgctg 330
<210> 76
<211> 363
<212> DNA
<213> 人工序列（Artificial Sequence）
<400> 76
caagtgcaac tggtgcagag cggcgctgag gtgaagaagc ccggcagcag cgtgaaggtc 60
agctgcaagg ccagcgaaga cacattcagc tcctacgtga tcagctgggt gagacaagct 120
cccggccaag gactggagtg gatgggagcc ttcatccctc tgctgggcag agtgcactat 180
gcccaagagt tccaaggcag actgacaatc accgccgacg agtccaccgg caccgcttac 240
atggagctga aaggactgag gagcgacgac accgccatgt actactgcgc cagagatcaa 300
ggcttcgccg gcgatgacgc cttcgatatc tggggccaag gcacaatggt gacagtgagc 360
agc 363
<210> 77
<211> 324
<212> DNA
<213> 人工序列（Artificial Sequence）
<400> 77
cagcccgtgc tgacccaaga ccccgtggtg tccgtggctc tgggacagac cgtgaggatc 60
acatgccaag gcgattctct gaggagctac tatgccacat ggtaccagca gaaacccgga 120
ctggcccccg tgagagtcat cttcggaaag aactctaggc ccagcggcat ccccgataga 180
ttcagcggca gcagcagcgg caataccgcc tccctcacca tcaccggcgc ccaagccgag 240
gacgaagccg actactactg caacagctgg gacaacagcg ccaaccatcc cgtgttcggc 300
ggcggcacaa agctgacagt gctc 324
<210> 78
<211> 366
<212> DNA
<213> 人工序列（Artificial Sequence）
<400> 78
gaggtgcagc tcgtgcagtc cggcgccgaa gtgaggaagc ccggcagctc cgtgaaggtg 60
agctgtaagg ccagcggcga caacttcaac aactacggca tcacatgggt gagacaagcc 120
cccggccaag gactggagtg gatgggaaga ctgatcaccg tgctgggact ggacaactac 180
gcccagaagt tccaaggaag actgacaatc accgctgacg agtccaccgg caccgcctat 240
atggaactga ccggactgga gcccgaggat accgccgtgt actattgcgc tagagacatc 300
atgtcccccg aggccatcga tgccttcgac gtgtggggac aaggcacact ggtgaccgtg 360
agctcc 366
<210> 79
<211> 321
<212> DNA
<213> 人工序列（Artificial Sequence）
<400> 79
gacatccaga tgacacagag cccttcctct ctgagcgcct ccgtcggaga tagagtgacc 60
atcacatgca gagcctccca agacgtcagc aactatctga actggtacca gcagaagccc 120
ggcaaggccc ctaaactgct gatctatggc gccagcaata gacagaccgg cgtgccttcc 180
agattctccg gcagcggaag cggcaccgat ttcacactga caatttcctc tctgcagccc 240
gaggactttg ccacctacta ctgccagcaa gaggacagat tccctacaac cttcggccaa 300
ggcacaaagg tggagatcaa a 321
<210> 80
<211> 366
<212> DNA
<213> 人工序列（Artificial Sequence）
<400> 80
gaagtgcagc tggtgcagag cggagctgag gtgagaaagc ccggcagcag cgtcaaggtg 60
agctgtaagg ccagcggcga caacttcaac aactacggca tcacatgggt gaggcaagcc 120
cccggccaag gcctcgagtg gatgggaaga ctgatcaccg tgctcggact ggacaactac 180
gcccagaagt tccaaggcag actgacaatc accgccgatg agtccaccgg aacagcctac 240
atggagctga ccggactgga gcccgaagac acagctgtgt actactgcgc tagagacatc 300
atgtcccccg aggccatcga tgcctttgac gtgtggggcc aaggcacact ggtgacagtc 360
agcagc 366
<210> 81
<211> 45
<212> DNA
<213> 人工序列（Artificial Sequence）
<400> 81
ggaggaggag gcagcggagg cggaggcagc ggaggaggcg gcagc 45
<210> 82
<211> 110
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 82
Gln Ser Val Leu Thr Gln Pro Ala Ser Val Ser Gly Ser Pro Gly Gln
1 5 10 15
Ser Val Thr Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr
20 25 30
Asn Tyr Val Ser Trp Tyr Gln Gln His Pro Gly Lys Pro Pro Lys Leu
35 40 45
Met Ile Tyr Glu Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe
50 55 60
Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr Ile Ser Gly Leu
65 70 75 80
Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser His Thr Ser Ser
85 90 95
Asn Thr Leu Ile Phe Gly Gly Gly Thr Lys Val Thr Val Leu
100 105 110
<210> 83
<211> 118
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 83
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu
1 5 10 15
Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Thr Phe Thr Asn Tyr
20 25 30
Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Arg Ile Tyr Pro Ser Asp Ser Tyr Thr Asn Tyr Ser Pro Ser Phe
50 55 60
Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys
85 90 95
Ala Arg Asp Leu Glu Pro Thr His His Tyr Ser Trp Gly Gln Gly Thr
100 105 110
Leu Val Thr Val Ser Ser
115
<210> 84
<211> 110
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 84
Leu Pro Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln
1 5 10 15
Arg Val Thr Ile Ser Cys Ser Gly Ser Ser Ser Asn Ile Gly Ser Asn
20 25 30
Ala Val Asp Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu Leu
35 40 45
Ile Tyr Thr Asn Asn Arg Arg Pro Ser Gly Val Pro Asp Arg Phe Ser
50 55 60
Gly Ser Lys Ser Gly Thr Ser Gly Ser Leu Ala Ile Ser Gly Leu Gln
65 70 75 80
Phe Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Ala Trp Asp Asp Ser Leu
85 90 95
Ser Gly Val Ile Phe Gly Gly Gly Thr Lys Val Thr Val Leu
100 105 110
<210> 85
<211> 121
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 85
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Glu Asp Thr Phe Ser Ser Tyr
20 25 30
Val Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Phe Ile Pro Leu Leu Gly Arg Val His Tyr Ala Gln Glu Phe
50 55 60
Gln Gly Arg Leu Thr Ile Thr Ala Asp Glu Ser Thr Gly Thr Ala Tyr
65 70 75 80
Met Glu Leu Lys Gly Leu Arg Ser Asp Asp Thr Ala Met Tyr Tyr Cys
85 90 95
Ala Arg Asp Gln Gly Phe Ala Gly Asp Asp Ala Phe Asp Ile Trp Gly
100 105 110
Gln Gly Thr Met Val Thr Val Ser Ser
115 120
<210> 86
<211> 108
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 86
Gln Pro Val Leu Thr Gln Asp Pro Val Val Ser Val Ala Leu Gly Gln
1 5 10 15
Thr Val Arg Ile Thr Cys Gln Gly Asp Ser Leu Arg Ser Tyr Tyr Ala
20 25 30
Thr Trp Tyr Gln Gln Lys Pro Gly Leu Ala Pro Val Arg Val Ile Phe
35 40 45
Gly Lys Asn Ser Arg Pro Ser Gly Ile Pro Asp Arg Phe Ser Gly Ser
50 55 60
Ser Ser Gly Asn Thr Ala Ser Leu Thr Ile Thr Gly Ala Gln Ala Glu
65 70 75 80
Asp Glu Ala Asp Tyr Tyr Cys Asn Ser Trp Asp Asn Ser Ala Asn His
85 90 95
Pro Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
100 105
<210> 87
<211> 122
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 87
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Arg Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Asp Asn Phe Asn Asn Tyr
20 25 30
Gly Ile Thr Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Arg Leu Ile Thr Val Leu Gly Leu Asp Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Leu Thr Ile Thr Ala Asp Glu Ser Thr Gly Thr Ala Tyr
65 70 75 80
Met Glu Leu Thr Gly Leu Glu Pro Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Ile Met Ser Pro Glu Ala Ile Asp Ala Phe Asp Val Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 88
<211> 107
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 88
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Val Ser Asn Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Gly Ala Ser Asn Arg Gln Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Glu Asp Arg Phe Pro Thr
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 89
<211> 122
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 89
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Arg Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Asp Asn Phe Asn Asn Tyr
20 25 30
Gly Ile Thr Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Arg Leu Ile Thr Val Leu Gly Leu Asp Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Leu Thr Ile Thr Ala Asp Glu Ser Thr Gly Thr Ala Tyr
65 70 75 80
Met Glu Leu Thr Gly Leu Glu Pro Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Ile Met Ser Pro Glu Ala Ile Asp Ala Phe Asp Val Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 90
<211> 15
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 90
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
1 5 10 15
<210> 91
<211> 717
<212> DNA
<213> 人工序列（Artificial Sequence）
<400> 91
gaggtccaac tgcagcagtc tggagctgag ctgatgaagc ctgggacttc agtgaagatg 60
tcctgcaagg ctgctggata caccttcact aagtactgga taggttgggt aaagcagagg 120
cctggacatg gccttgagtg gattggagat atttaccctg gaggtggtta tactctcttc 180
aatgagaagt tcaagggcaa ggccacactg actgcagaca catcctccag cacagcctac 240
atgcagctca gcagcctgac atctgaggac tctgccatct attactgtgc aagagggaac 300
tactggggcc aaggcaccac tctcaccgtc tcctcaggtg gtggtggtag cggcggcggc 360
ggctctggtg gtggtggatc cgatgttgtg atgacccaaa ctccactcac tttgtcggtt 420
accattggac aaccagcctc catctcttgc aagtcaagtc agagcctctt agatagtgat 480
ggaaagacat atttgaattg gttgttacag aggccaggcc agtctccaaa gcgcctaatc 540
tatctggtgt ctaaactgga ctctggagtc cctgacaggt tcactggcag tggatcaggg 600
acagatttca cactgaaaat cagcagagtg gaggctgagg atttgggagt ttattattgc 660
tggcaaggta cacattttcc tcacacgttc ggagggggca ccaagctgga aatgaaa 717
<210> 92
<211> 239
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 92
Glu Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Met Lys Pro Gly Thr
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ala Gly Tyr Thr Phe Thr Lys Tyr
20 25 30
Trp Ile Gly Trp Val Lys Gln Arg Pro Gly His Gly Leu Glu Trp Ile
35 40 45
Gly Asp Ile Tyr Pro Gly Gly Gly Tyr Thr Leu Phe Asn Glu Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Ala Asp Thr Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Ile Tyr Tyr Cys
85 90 95
Ala Arg Gly Asn Tyr Trp Gly Gln Gly Thr Thr Leu Thr Val Ser Ser
100 105 110
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp
115 120 125
Val Val Met Thr Gln Thr Pro Leu Thr Leu Ser Val Thr Ile Gly Gln
130 135 140
Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Leu Asp Ser Asp
145 150 155 160
Gly Lys Thr Tyr Leu Asn Trp Leu Leu Gln Arg Pro Gly Gln Ser Pro
165 170 175
Lys Arg Leu Ile Tyr Leu Val Ser Lys Leu Asp Ser Gly Val Pro Asp
180 185 190
Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile Ser
195 200 205
Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Tyr Cys Trp Gln Gly Thr
210 215 220
His Phe Pro His Thr Phe Gly Gly Gly Thr Lys Leu Glu Met Lys
225 230 235
<210> 93
<211> 112
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 93
Glu Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Met Lys Pro Gly Thr
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ala Gly Tyr Thr Phe Thr Lys Tyr
20 25 30
Trp Ile Gly Trp Val Lys Gln Arg Pro Gly His Gly Leu Glu Trp Ile
35 40 45
Gly Asp Ile Tyr Pro Gly Gly Gly Tyr Thr Leu Phe Asn Glu Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Ala Asp Thr Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Ile Tyr Tyr Cys
85 90 95
Ala Arg Gly Asn Tyr Trp Gly Gln Gly Thr Thr Leu Thr Val Ser Ser
100 105 110
<210> 94
<211> 112
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 94
Asp Val Val Met Thr Gln Thr Pro Leu Thr Leu Ser Val Thr Ile Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Leu Asp Ser
20 25 30
Asp Gly Lys Thr Tyr Leu Asn Trp Leu Leu Gln Arg Pro Gly Gln Ser
35 40 45
Pro Lys Arg Leu Ile Tyr Leu Val Ser Lys Leu Asp Ser Gly Val Pro
50 55 60
Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Tyr Cys Trp Gln Gly
85 90 95
Thr His Phe Pro His Thr Phe Gly Gly Gly Thr Lys Leu Glu Met Lys
100 105 110
<210> 95
<211> 708
<212> DNA
<213> 人工序列（Artificial Sequence）
<400> 95
caggtcaagc tgcaacagtc tgggcccgag ctggtgaggc ctggggcttc agtgaagatg 60
tcctgcaagg cttcaggcta taccttcacc acctactgga tgcactgggt gaaacagagg 120
ccaggacaag gccttgagtg gattggcatg attgatccct ccaatagtga cactaggtta 180
aatcagaagt tcaaggacaa ggccacattg aatgttgaca catcctccaa cacagcctac 240
atgcacctca gcagcctgac atctgaggac tctgcagtct attactgtac attaggtggg 300
actgagtatt ggggccaagg cgccactctc acagtctcct caggtggtgg tggtagcggc 360
ggcggcggct ctggtggtgg tggatccagt attgtgatga cccagtctcc agccaccctg 420
tctgtgactc caggagatag agtctctctt tcctgcaggg ccagccagag tattggcgac 480
tacctacact ggtttcaaca aaaatcacat gagtctccaa ggcttctcat caaatatgct 540
tcccaatcca tctctgggat cccctccagg ttcagtggca gtggatcagg gtcagatttc 600
actctcatta tcaacactat ggaacctgaa gatgttggag tgtattactg tcaaaatgct 660
cacacctatc cgtacacgtt cggagggggc accaagctgg aaatcaaa 708
<210> 96
<211> 236
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 96
Gln Val Lys Leu Gln Gln Ser Gly Pro Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Thr Tyr
20 25 30
Trp Met His Trp Val Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Met Ile Asp Pro Ser Asn Ser Asp Thr Arg Leu Asn Gln Lys Phe
50 55 60
Lys Asp Lys Ala Thr Leu Asn Val Asp Thr Ser Ser Asn Thr Ala Tyr
65 70 75 80
Met His Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Leu Gly Gly Thr Glu Tyr Trp Gly Gln Gly Ala Thr Leu Thr Val
100 105 110
Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
115 120 125
Ser Ser Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Val Thr Pro
130 135 140
Gly Asp Arg Val Ser Leu Ser Cys Arg Ala Ser Gln Ser Ile Gly Asp
145 150 155 160
Tyr Leu His Trp Phe Gln Gln Lys Ser His Glu Ser Pro Arg Leu Leu
165 170 175
Ile Lys Tyr Ala Ser Gln Ser Ile Ser Gly Ile Pro Ser Arg Phe Ser
180 185 190
Gly Ser Gly Ser Gly Ser Asp Phe Thr Leu Ile Ile Asn Thr Met Glu
195 200 205
Pro Glu Asp Val Gly Val Tyr Tyr Cys Gln Asn Ala His Thr Tyr Pro
210 215 220
Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
225 230 235
<210> 97
<211> 114
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 97
Gln Val Lys Leu Gln Gln Ser Gly Pro Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Thr Tyr
20 25 30
Trp Met His Trp Val Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Met Ile Asp Pro Ser Asn Ser Asp Thr Arg Leu Asn Gln Lys Phe
50 55 60
Lys Asp Lys Ala Thr Leu Asn Val Asp Thr Ser Ser Asn Thr Ala Tyr
65 70 75 80
Met His Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Leu Gly Gly Thr Glu Tyr Trp Gly Gln Gly Ala Thr Leu Thr Val
100 105 110
Ser Ser
<210> 98
<211> 107
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 98
Ser Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Val Thr Pro Gly
1 5 10 15
Asp Arg Val Ser Leu Ser Cys Arg Ala Ser Gln Ser Ile Gly Asp Tyr
20 25 30
Leu His Trp Phe Gln Gln Lys Ser His Glu Ser Pro Arg Leu Leu Ile
35 40 45
Lys Tyr Ala Ser Gln Ser Ile Ser Gly Ile Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Ser Asp Phe Thr Leu Ile Ile Asn Thr Met Glu Pro
65 70 75 80
Glu Asp Val Gly Val Tyr Tyr Cys Gln Asn Ala His Thr Tyr Pro Tyr
85 90 95
Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 99
<211> 738
<212> DNA
<213> 人工序列（Artificial Sequence）
<400> 99
gaagtgaagc tgaagcagtc tggggctgaa ctggtgaagc ctggggcttc agtgaagttg 60
tcctgcaagg cttctggcta caccctcacc agttactata tttactgggt gaagcagagg 120
cctggacaag gccttgagtg gattgggggg attagtccta gcaatggtaa tacttacttc 180
actgagaagt tcaagaacat ggccacactg actgtagaca aatcctccaa cacagcctac 240
atgcaactca gcagcctgac atctgaggac tctgcggtct attactgtgc aagaaactat 300
gattacgacg tggggtttgc ttactggggc caagggactc tggtcacagt ctcctcaggt 360
ggtggtggta gcggcggcgg cggctctggt ggtggtggat ccgatgttgt gatgacccaa 420
actccactct ccctgcctgt cagtcttgga gatcaagcct ccatctcttg cagatctagt 480
cagagcattg tacatagtaa tggaaacacc tatttagaat ggtacctgca gaaaccaggc 540
cagtctccaa agctcctgat ctacaaagtt tccaaccgat tttctggggt cccagacagg 600
ttcagtggca gtggatcagg gacagatttc acactcaaga tcagcagagt ggaggctgag 660
gatctgggag tttattactg ctttcaaggt tcacatgttc cattcacgtt cggctcgggg 720
accaagctgg aaatcaaa 738
<210> 100
<211> 246
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 100
Glu Val Lys Leu Lys Gln Ser Gly Ala Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Leu Ser Cys Lys Ala Ser Gly Tyr Thr Leu Thr Ser Tyr
20 25 30
Tyr Ile Tyr Trp Val Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Gly Ile Ser Pro Ser Asn Gly Asn Thr Tyr Phe Thr Glu Lys Phe
50 55 60
Lys Asn Met Ala Thr Leu Thr Val Asp Lys Ser Ser Asn Thr Ala Tyr
65 70 75 80
Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asn Tyr Asp Tyr Asp Val Gly Phe Ala Tyr Trp Gly Gln Gly
100 105 110
Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
115 120 125
Ser Gly Gly Gly Gly Ser Asp Val Val Met Thr Gln Thr Pro Leu Ser
130 135 140
Leu Pro Val Ser Leu Gly Asp Gln Ala Ser Ile Ser Cys Arg Ser Ser
145 150 155 160
Gln Ser Ile Val His Ser Asn Gly Asn Thr Tyr Leu Glu Trp Tyr Leu
165 170 175
Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile Tyr Lys Val Ser Asn
180 185 190
Arg Phe Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr
195 200 205
Asp Phe Thr Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Leu Gly Val
210 215 220
Tyr Tyr Cys Phe Gln Gly Ser His Val Pro Phe Thr Phe Gly Ser Gly
225 230 235 240
Thr Lys Leu Glu Ile Lys
245
<210> 101
<211> 119
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 101
Glu Val Lys Leu Lys Gln Ser Gly Ala Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Leu Ser Cys Lys Ala Ser Gly Tyr Thr Leu Thr Ser Tyr
20 25 30
Tyr Ile Tyr Trp Val Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Gly Ile Ser Pro Ser Asn Gly Asn Thr Tyr Phe Thr Glu Lys Phe
50 55 60
Lys Asn Met Ala Thr Leu Thr Val Asp Lys Ser Ser Asn Thr Ala Tyr
65 70 75 80
Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asn Tyr Asp Tyr Asp Val Gly Phe Ala Tyr Trp Gly Gln Gly
100 105 110
Thr Leu Val Thr Val Ser Ser
115
<210> 102
<211> 112
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 102
Asp Val Val Met Thr Gln Thr Pro Leu Ser Leu Pro Val Ser Leu Gly
1 5 10 15
Asp Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Ile Val His Ser
20 25 30
Asn Gly Asn Thr Tyr Leu Glu Trp Tyr Leu Gln Lys Pro Gly Gln Ser
35 40 45
Pro Lys Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Tyr Cys Phe Gln Gly
85 90 95
Ser His Val Pro Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 103
<211> 726
<212> DNA
<213> 人工序列（Artificial Sequence）
<400> 103
caggtgcagc tgaaggagtc tgggggaggc ttagtgcagc ctggggagtc cctgaaactc 60
tcctgtgaat ccagtgaatt cccattccct tcccatgaca tgtcttgggt ccgcaagact 120
ccggagaaga ggctggagtt ggtcgcagcc attaatagtg atggtggtag cacctactat 180
ccagacacca tggagagacg attcatcatc tccagagaca ataccaagaa gaccctgtac 240
ctgcaaatga gcagtctgag gtctgaggac acagccttgt attactgtgc aagcctaccc 300
acgtttgctt actggggcca agggactctg gtcactgtct ctgcaggtgg tggtggtagc 360
ggcggcggcg gctctggtgg tggtggatcc agtattgtga tgacccaaac tccactcact 420
ttgtcggtta ccattggaca accagcctct atctcttgca agtcaagtca gagcctctta 480
tatagtgatg gacaaaccta tttgaattgg ttattacaga ggccaggcca gtctccaaag 540
cgcctaatct atctggtgtc taaactggac tctggagtcc ctgacaggtt cactggcagt 600
ggatcaggta cagattttac actgaaaatc agcagagtgg aggctgagga tttgggagtt 660
tattactgcg tgcaaactac acattttccg tacacgttcg gaggggggac caagctggaa 720
atgaaa 726
<210> 104
<211> 242
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 104
Gln Val Gln Leu Lys Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Glu
1 5 10 15
Ser Leu Lys Leu Ser Cys Glu Ser Ser Glu Phe Pro Phe Pro Ser His
20 25 30
Asp Met Ser Trp Val Arg Lys Thr Pro Glu Lys Arg Leu Glu Leu Val
35 40 45
Ala Ala Ile Asn Ser Asp Gly Gly Ser Thr Tyr Tyr Pro Asp Thr Met
50 55 60
Glu Arg Arg Phe Ile Ile Ser Arg Asp Asn Thr Lys Lys Thr Leu Tyr
65 70 75 80
Leu Gln Met Ser Ser Leu Arg Ser Glu Asp Thr Ala Leu Tyr Tyr Cys
85 90 95
Ala Ser Leu Pro Thr Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly
115 120 125
Gly Ser Ser Ile Val Met Thr Gln Thr Pro Leu Thr Leu Ser Val Thr
130 135 140
Ile Gly Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Leu
145 150 155 160
Tyr Ser Asp Gly Gln Thr Tyr Leu Asn Trp Leu Leu Gln Arg Pro Gly
165 170 175
Gln Ser Pro Lys Arg Leu Ile Tyr Leu Val Ser Lys Leu Asp Ser Gly
180 185 190
Val Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu
195 200 205
Lys Ile Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Tyr Cys Val
210 215 220
Gln Thr Thr His Phe Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu
225 230 235 240
Met Lys
<210> 105
<211> 115
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 105
Gln Val Gln Leu Lys Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Glu
1 5 10 15
Ser Leu Lys Leu Ser Cys Glu Ser Ser Glu Phe Pro Phe Pro Ser His
20 25 30
Asp Met Ser Trp Val Arg Lys Thr Pro Glu Lys Arg Leu Glu Leu Val
35 40 45
Ala Ala Ile Asn Ser Asp Gly Gly Ser Thr Tyr Tyr Pro Asp Thr Met
50 55 60
Glu Arg Arg Phe Ile Ile Ser Arg Asp Asn Thr Lys Lys Thr Leu Tyr
65 70 75 80
Leu Gln Met Ser Ser Leu Arg Ser Glu Asp Thr Ala Leu Tyr Tyr Cys
85 90 95
Ala Ser Leu Pro Thr Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ala
115
<210> 106
<211> 112
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 106
Ser Ile Val Met Thr Gln Thr Pro Leu Thr Leu Ser Val Thr Ile Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Leu Tyr Ser
20 25 30
Asp Gly Gln Thr Tyr Leu Asn Trp Leu Leu Gln Arg Pro Gly Gln Ser
35 40 45
Pro Lys Arg Leu Ile Tyr Leu Val Ser Lys Leu Asp Ser Gly Val Pro
50 55 60
Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Tyr Cys Val Gln Thr
85 90 95
Thr His Phe Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Met Lys
100 105 110
<210> 107
<211> 720
<212> DNA
<213> 人工序列（Artificial Sequence）
<400> 107
caggttcagc tgcagcagtc tggggcagag cttgtgaggt caggggcctc agtcaagttg 60
tcctgcacag attctggctt caacattaaa gactactata tgaactgggt gaaacagcgg 120
cctgaacagg gcctggagtg gattggatgg attgatcctg aaaatggtgt tactcaatat 180
gacccgaagt tccagggcaa ggccactgtg actgcagaca cattctccaa cacagcctac 240
ctgcagctca gcagcctgac atctgaggac actgccgtct attactgtaa tgcaaactat 300
aagtacgact ggtttggtta ctggggccaa gggactctgg tcactgtctc tgcaggtggt 360
ggtggtagcg gcggcggcgg ctctggtggt ggtggatcca acattgtaat gacccagtct 420
ccatcctcct tatctgcctc tctgggagaa agagtcagtc tcacttgtcg ggcaagtcag 480
gaaattagtg gttacttaag ctggcttcag cagaaaccag atggaactat taaacgcctg 540
atctacgccg catccacttt agattctggt gtcccagaaa ggttcagtgg cagtaggtct 600
gggtcagatt attctctcac catcagcagc cttgagtctg aagattttgc agactattac 660
tgtctacaat atgctagtta tccgtggacg ttcggtggag ggaccaagct ggaaatgaaa 720
<210> 108
<211> 240
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 108
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Ser Gly Ala
1 5 10 15
Ser Val Lys Leu Ser Cys Thr Asp Ser Gly Phe Asn Ile Lys Asp Tyr
20 25 30
Tyr Met Asn Trp Val Lys Gln Arg Pro Glu Gln Gly Leu Glu Trp Ile
35 40 45
Gly Trp Ile Asp Pro Glu Asn Gly Val Thr Gln Tyr Asp Pro Lys Phe
50 55 60
Gln Gly Lys Ala Thr Val Thr Ala Asp Thr Phe Ser Asn Thr Ala Tyr
65 70 75 80
Leu Gln Leu Ser Ser Leu Thr Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Asn Ala Asn Tyr Lys Tyr Asp Trp Phe Gly Tyr Trp Gly Gln Gly Thr
100 105 110
Leu Val Thr Val Ser Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
115 120 125
Gly Gly Gly Gly Ser Asn Ile Val Met Thr Gln Ser Pro Ser Ser Leu
130 135 140
Ser Ala Ser Leu Gly Glu Arg Val Ser Leu Thr Cys Arg Ala Ser Gln
145 150 155 160
Glu Ile Ser Gly Tyr Leu Ser Trp Leu Gln Gln Lys Pro Asp Gly Thr
165 170 175
Ile Lys Arg Leu Ile Tyr Ala Ala Ser Thr Leu Asp Ser Gly Val Pro
180 185 190
Glu Arg Phe Ser Gly Ser Arg Ser Gly Ser Asp Tyr Ser Leu Thr Ile
195 200 205
Ser Ser Leu Glu Ser Glu Asp Phe Ala Asp Tyr Tyr Cys Leu Gln Tyr
210 215 220
Ala Ser Tyr Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu Met Lys
225 230 235 240
<210> 109
<211> 118
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 109
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Ser Gly Ala
1 5 10 15
Ser Val Lys Leu Ser Cys Thr Asp Ser Gly Phe Asn Ile Lys Asp Tyr
20 25 30
Tyr Met Asn Trp Val Lys Gln Arg Pro Glu Gln Gly Leu Glu Trp Ile
35 40 45
Gly Trp Ile Asp Pro Glu Asn Gly Val Thr Gln Tyr Asp Pro Lys Phe
50 55 60
Gln Gly Lys Ala Thr Val Thr Ala Asp Thr Phe Ser Asn Thr Ala Tyr
65 70 75 80
Leu Gln Leu Ser Ser Leu Thr Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Asn Ala Asn Tyr Lys Tyr Asp Trp Phe Gly Tyr Trp Gly Gln Gly Thr
100 105 110
Leu Val Thr Val Ser Ala
115
<210> 110
<211> 107
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 110
Asn Ile Val Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Leu Gly
1 5 10 15
Glu Arg Val Ser Leu Thr Cys Arg Ala Ser Gln Glu Ile Ser Gly Tyr
20 25 30
Leu Ser Trp Leu Gln Gln Lys Pro Asp Gly Thr Ile Lys Arg Leu Ile
35 40 45
Tyr Ala Ala Ser Thr Leu Asp Ser Gly Val Pro Glu Arg Phe Ser Gly
50 55 60
Ser Arg Ser Gly Ser Asp Tyr Ser Leu Thr Ile Ser Ser Leu Glu Ser
65 70 75 80
Glu Asp Phe Ala Asp Tyr Tyr Cys Leu Gln Tyr Ala Ser Tyr Pro Trp
85 90 95
Thr Phe Gly Gly Gly Thr Lys Leu Glu Met Lys
100 105
<210> 111
<211> 723
<212> DNA
<213> 人工序列（Artificial Sequence）
<400> 111
caggtgcagc tgaagcagtc tgggcctggg ctggtgaggc ctggggcttc agtgacgatg 60
tcctgcaagg cttcaggcta taccttcacc agcaactgga tgcactgggt taaacagagg 120
cctggacaag gccttgattg gattggcatg attgatcctt ccaatagtga cactaggtta 180
aatcagaagt tcaaggacaa ggccacattg aatgtagaca aatcctccaa cacagcctac 240
atgcagctca gcagcctgac gtctgatgac tctgcagtct attactgtat gagagggggc 300
ggcgactact ggggccaagg caccactctc acagtctcct caggtggtgg tggtagcggc 360
ggcggctctg gtggtggtgg atccgacatt gtgatgtcac agtctccatc ctccctagct 420
gtgtcagttg gagagaaggt tactatgagc tgcaagtcca gtcagagcct tttatatagt 480
agcaatcaaa agaactactt ggcctggtac cagcagaaac cagggcagtc tcctaaactg 540
ctgatttact gggcatccac tagggaatct ggggtccctg atcgcttcac aggcagtgga 600
tctgggacag atttcactct caccatcagc agtgtgaagg ctgaagacct ggcagtttat 660
tactgtcagc aatattatag ctatccgtac acgttcggag gggggaccaa gctggaaatg 720
aaa 723
<210> 112
<211> 242
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 112
Gln Val Gln Leu Lys Gln Ser Gly Pro Gly Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Asn
20 25 30
Trp Met His Trp Val Lys Gln Arg Pro Gly Gln Gly Leu Asp Trp Ile
35 40 45
Gly Met Ile Asp Pro Ser Asn Ser Asp Thr Arg Leu Asn Gln Lys Phe
50 55 60
Lys Asp Lys Ala Thr Leu Asn Val Asp Lys Ser Ser Asn Thr Ala Tyr
65 70 75 80
Met Gln Leu Ser Ser Leu Thr Ser Asp Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Met Arg Gly Gly Gly Asp Tyr Trp Gly Gln Gly Thr Thr Leu Thr Val
100 105 110
Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
115 120 125
Ser Asp Ile Val Met Ser Gln Ser Pro Ser Ser Leu Ala Val Ser Val
130 135 140
Gly Glu Lys Val Thr Met Ser Cys Lys Ser Ser Gln Ser Leu Leu Tyr
145 150 155 160
Ser Ser Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly
165 170 175
Gln Ser Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly
180 185 190
Val Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu
195 200 205
Thr Ile Ser Ser Val Lys Ala Glu Asp Leu Ala Val Tyr Tyr Cys Gln
210 215 220
Gln Tyr Tyr Ser Tyr Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu
225 230 235 240
Met Lys
<210> 113
<211> 114
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 113
Gln Val Gln Leu Lys Gln Ser Gly Pro Gly Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Asn
20 25 30
Trp Met His Trp Val Lys Gln Arg Pro Gly Gln Gly Leu Asp Trp Ile
35 40 45
Gly Met Ile Asp Pro Ser Asn Ser Asp Thr Arg Leu Asn Gln Lys Phe
50 55 60
Lys Asp Lys Ala Thr Leu Asn Val Asp Lys Ser Ser Asn Thr Ala Tyr
65 70 75 80
Met Gln Leu Ser Ser Leu Thr Ser Asp Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Met Arg Gly Gly Gly Asp Tyr Trp Gly Gln Gly Thr Thr Leu Thr Val
100 105 110
Ser Ser
<210> 114
<211> 113
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 114
Asp Ile Val Met Ser Gln Ser Pro Ser Ser Leu Ala Val Ser Val Gly
1 5 10 15
Glu Lys Val Thr Met Ser Cys Lys Ser Ser Gln Ser Leu Leu Tyr Ser
20 25 30
Ser Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
35 40 45
Ser Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val
50 55 60
Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
65 70 75 80
Ile Ser Ser Val Lys Ala Glu Asp Leu Ala Val Tyr Tyr Cys Gln Gln
85 90 95
Tyr Tyr Ser Tyr Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Met
100 105 110
Lys
<210> 115
<211> 720
<212> DNA
<213> 人工序列（Artificial Sequence）
<400> 115
gaggtgcagc tgaaggagtc tggggcagag cttgtgaggt caggggcctc agtcaagttg 60
tcctgcacag cttctgcctt caacattaaa gactactata tgaactggat gaagcagagg 120
cctgaacagg gcctggagtg gattggatgg attgatcctg agaatggtga tactaaatat 180
gccccgaagt tccagggcaa ggccactatc actgcagaca catcctccag cacagcctac 240
ctgcagctca ccagcctgac atctgaggac tctgccgtct tctattgtaa tgtaaactat 300
aagtacgact ggtttgctta ctggggccaa gggactctgg tcactgtctc tgcaggtggt 360
ggtggtagcg gcggcggcgg ctctggtggt ggtggatccg atgttgtgat gacccagtcc 420
caaaaattca tgtccacatc agtaggagac agggtcagcg tcacctgcaa ggccagtcag 480
aatgtgggta ctaatgtagc ctggtatcaa cagaaaccag ggcaatctcc tagagcactg 540
atttactcgg catcctaccg gtacagtgga gtccctgatc gcttcacagg cagtggatct 600
gggacagatt tcactctcac catcagcaat gtgcagtctg aagacttggc agagtatttc 660
tgtcagcaat ataacaccta tccgtggacg ttcggtgggg ggacaaagct ggaaataaaa 720
<210> 116
<211> 240
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 116
Glu Val Gln Leu Lys Glu Ser Gly Ala Glu Leu Val Arg Ser Gly Ala
1 5 10 15
Ser Val Lys Leu Ser Cys Thr Ala Ser Ala Phe Asn Ile Lys Asp Tyr
20 25 30
Tyr Met Asn Trp Met Lys Gln Arg Pro Glu Gln Gly Leu Glu Trp Ile
35 40 45
Gly Trp Ile Asp Pro Glu Asn Gly Asp Thr Lys Tyr Ala Pro Lys Phe
50 55 60
Gln Gly Lys Ala Thr Ile Thr Ala Asp Thr Ser Ser Ser Thr Ala Tyr
65 70 75 80
Leu Gln Leu Thr Ser Leu Thr Ser Glu Asp Ser Ala Val Phe Tyr Cys
85 90 95
Asn Val Asn Tyr Lys Tyr Asp Trp Phe Ala Tyr Trp Gly Gln Gly Thr
100 105 110
Leu Val Thr Val Ser Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
115 120 125
Gly Gly Gly Gly Ser Asp Val Val Met Thr Gln Ser Gln Lys Phe Met
130 135 140
Ser Thr Ser Val Gly Asp Arg Val Ser Val Thr Cys Lys Ala Ser Gln
145 150 155 160
Asn Val Gly Thr Asn Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser
165 170 175
Pro Arg Ala Leu Ile Tyr Ser Ala Ser Tyr Arg Tyr Ser Gly Val Pro
180 185 190
Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile
195 200 205
Ser Asn Val Gln Ser Glu Asp Leu Ala Glu Tyr Phe Cys Gln Gln Tyr
210 215 220
Asn Thr Tyr Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
225 230 235 240
<210> 117
<211> 118
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 117
Glu Val Gln Leu Lys Glu Ser Gly Ala Glu Leu Val Arg Ser Gly Ala
1 5 10 15
Ser Val Lys Leu Ser Cys Thr Ala Ser Ala Phe Asn Ile Lys Asp Tyr
20 25 30
Tyr Met Asn Trp Met Lys Gln Arg Pro Glu Gln Gly Leu Glu Trp Ile
35 40 45
Gly Trp Ile Asp Pro Glu Asn Gly Asp Thr Lys Tyr Ala Pro Lys Phe
50 55 60
Gln Gly Lys Ala Thr Ile Thr Ala Asp Thr Ser Ser Ser Thr Ala Tyr
65 70 75 80
Leu Gln Leu Thr Ser Leu Thr Ser Glu Asp Ser Ala Val Phe Tyr Cys
85 90 95
Asn Val Asn Tyr Lys Tyr Asp Trp Phe Ala Tyr Trp Gly Gln Gly Thr
100 105 110
Leu Val Thr Val Ser Ala
115
<210> 118
<211> 107
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 118
Asp Val Val Met Thr Gln Ser Gln Lys Phe Met Ser Thr Ser Val Gly
1 5 10 15
Asp Arg Val Ser Val Thr Cys Lys Ala Ser Gln Asn Val Gly Thr Asn
20 25 30
Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Arg Ala Leu Ile
35 40 45
Tyr Ser Ala Ser Tyr Arg Tyr Ser Gly Val Pro Asp Arg Phe Thr Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Asn Val Gln Ser
65 70 75 80
Glu Asp Leu Ala Glu Tyr Phe Cys Gln Gln Tyr Asn Thr Tyr Pro Trp
85 90 95
Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 119
<211> 720
<212> DNA
<213> 人工序列（Artificial Sequence）
<400> 119
caggtccaac tgcagcagtc tgggcctgag ctggtgaggc ctggggcttc agtgacgatg 60
tcctgcaagg cttcaggcta taccttcacc agcaactgga tgcactgggt taaacagagg 120
cctggacaag gccttgattg gattggcatg attgatcctt ccaatagtga cactaggtta 180
aatcagaagt tcaaggacaa ggccacattg aatgtagaca aatcctccaa cacagcctac 240
atgcagctca gcagcctgac gtctgaggac tctgcagtct attactgtat gagagggggc 300
ggcgactact ggggccaagg caccactctc acagtctcct caggtggtgg tggtagcggc 360
ggcggcggct ctggtggtgg tggatccgac attgtgatga cccagtctcc agcttctttg 420
gctgtgtctc tagggcagag ggccaccatc tcctgcaagg ccagccaaag tgttgattat 480
gatggtgata gttatatgaa ctggtaccaa cagaaaccag gacagccacc caaactcctc 540
atctatgctg catccaatct agaatctggg atcccagcca ggtttagtgg cagtgggtct 600
gggacagact tcaccctcaa catccatcct gtggaggagg aggatgctgc aacctattac 660
tgtcagcaca gttgggagat tccgtacacg ttcggagggg gcaccaagct ggaaatgaaa 720
<210> 120
<211> 240
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 120
Gln Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Asn
20 25 30
Trp Met His Trp Val Lys Gln Arg Pro Gly Gln Gly Leu Asp Trp Ile
35 40 45
Gly Met Ile Asp Pro Ser Asn Ser Asp Thr Arg Leu Asn Gln Lys Phe
50 55 60
Lys Asp Lys Ala Thr Leu Asn Val Asp Lys Ser Ser Asn Thr Ala Tyr
65 70 75 80
Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Met Arg Gly Gly Gly Asp Tyr Trp Gly Gln Gly Thr Thr Leu Thr Val
100 105 110
Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
115 120 125
Ser Asp Ile Val Met Thr Gln Ser Pro Ala Ser Leu Ala Val Ser Leu
130 135 140
Gly Gln Arg Ala Thr Ile Ser Cys Lys Ala Ser Gln Ser Val Asp Tyr
145 150 155 160
Asp Gly Asp Ser Tyr Met Asn Trp Tyr Gln Gln Lys Pro Gly Gln Pro
165 170 175
Pro Lys Leu Leu Ile Tyr Ala Ala Ser Asn Leu Glu Ser Gly Ile Pro
180 185 190
Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Asn Ile
195 200 205
His Pro Val Glu Glu Glu Asp Ala Ala Thr Tyr Tyr Cys Gln His Ser
210 215 220
Trp Glu Ile Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Met Lys
225 230 235 240
<210> 121
<211> 114
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 121
Gln Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Asn
20 25 30
Trp Met His Trp Val Lys Gln Arg Pro Gly Gln Gly Leu Asp Trp Ile
35 40 45
Gly Met Ile Asp Pro Ser Asn Ser Asp Thr Arg Leu Asn Gln Lys Phe
50 55 60
Lys Asp Lys Ala Thr Leu Asn Val Asp Lys Ser Ser Asn Thr Ala Tyr
65 70 75 80
Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Met Arg Gly Gly Gly Asp Tyr Trp Gly Gln Gly Thr Thr Leu Thr Val
100 105 110
Ser Ser
<210> 122
<211> 111
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 122
Asp Ile Val Met Thr Gln Ser Pro Ala Ser Leu Ala Val Ser Leu Gly
1 5 10 15
Gln Arg Ala Thr Ile Ser Cys Lys Ala Ser Gln Ser Val Asp Tyr Asp
20 25 30
Gly Asp Ser Tyr Met Asn Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro
35 40 45
Lys Leu Leu Ile Tyr Ala Ala Ser Asn Leu Glu Ser Gly Ile Pro Ala
50 55 60
Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Asn Ile His
65 70 75 80
Pro Val Glu Glu Glu Asp Ala Ala Thr Tyr Tyr Cys Gln His Ser Trp
85 90 95
Glu Ile Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Met Lys
100 105 110
<210> 123
<211> 499
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 123
Gln Val Gln Leu Gln Gln Ser Asp Ala Glu Leu Val Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp His
20 25 30
Ala Ile His Trp Val Lys Gln Lys Pro Glu Gln Gly Leu Glu Trp Ile
35 40 45
Gly His Phe Ser Pro Gly Asn Thr Asp Ile Lys Tyr Asn Asp Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Val Asp Arg Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Gln Leu Asn Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Phe Cys
85 90 95
Lys Thr Ser Thr Phe Phe Phe Asp Tyr Trp Gly Gln Gly Thr Thr Leu
100 105 110
Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
115 120 125
Gly Gly Ser Asp Ile Val Met Thr Gln Ser Pro Ser Ser Leu Thr Val
130 135 140
Thr Ala Gly Glu Lys Val Thr Met Ile Cys Lys Ser Ser Gln Ser Leu
145 150 155 160
Leu Asn Ser Gly Asp Gln Lys Asn Tyr Leu Thr Trp Tyr Gln Gln Lys
165 170 175
Pro Gly Gln Pro Pro Lys Leu Leu Ile Phe Trp Ala Ser Thr Arg Glu
180 185 190
Ser Gly Val Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe
195 200 205
Thr Leu Thr Ile Ser Ser Val Gln Ala Glu Asp Leu Ala Val Tyr Tyr
210 215 220
Cys Gln Asn Asp Tyr Ser Tyr Pro Leu Thr Phe Gly Ala Gly Thr Lys
225 230 235 240
Leu Glu Leu Lys Ser Gly Gly Gly Gly Ser Glu Val Gln Leu Val Glu
245 250 255
Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys
260 265 270
Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg
275 280 285
Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys
290 295 300
Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys Asp Arg Phe
305 310 315 320
Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn
325 330 335
Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly
340 345 350
Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly
355 360 365
Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
370 375 380
Ser Gly Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu
385 390 395 400
Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr
405 410 415
Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro
420 425 430
Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu Ala Pro
435 440 445
Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala
450 455 460
Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys
465 470 475 480
Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu
485 490 495
Thr Val Leu
<210> 124
<211> 501
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 124
Glu Val Lys Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Met Lys Leu Ser Cys Val Ala Ser Gly Phe Thr Phe Ser Asn Tyr
20 25 30
Trp Met Asn Trp Val Arg Gln Ser Pro Glu Lys Gly Leu Glu Trp Val
35 40 45
Ala Glu Ile Arg Leu Lys Ser Asn Asn Tyr Thr Thr His Tyr Ala Glu
50 55 60
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Ser Ser
65 70 75 80
Val Ser Leu Gln Met Asn Asn Leu Arg Val Glu Asp Thr Gly Ile Tyr
85 90 95
Tyr Cys Thr Arg His Tyr Tyr Phe Asp Tyr Trp Gly Gln Gly Thr Thr
100 105 110
Leu Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
115 120 125
Gly Gly Gly Ser Asp Ile Val Met Thr Gln Ala Ala Phe Ser Asn Pro
130 135 140
Val Thr Leu Gly Thr Ser Ala Ser Ile Ser Cys Arg Ser Ser Lys Ser
145 150 155 160
Leu Leu His Ser Asn Gly Ile Thr Tyr Phe Phe Trp Tyr Leu Gln Lys
165 170 175
Pro Gly Leu Ser Pro Gln Leu Leu Ile Tyr Gln Met Ser Asn Leu Ala
180 185 190
Ser Gly Val Pro Asp Arg Phe Ser Ser Ser Gly Ser Gly Thr Asp Phe
195 200 205
Thr Leu Arg Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr
210 215 220
Cys Ala Gln Asn Leu Glu Leu Pro Pro Thr Phe Gly Gly Gly Thr Lys
225 230 235 240
Leu Glu Ile Lys Arg Ala Ser Gly Gly Gly Gly Ser Glu Val Gln Leu
245 250 255
Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu
260 265 270
Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp
275 280 285
Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg
290 295 300
Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys Asp
305 310 315 320
Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln
325 330 335
Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg
340 345 350
His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly
355 360 365
Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly
370 375 380
Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro
385 390 395 400
Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser
405 410 415
Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln
420 425 430
Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu
435 440 445
Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys
450 455 460
Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr
465 470 475 480
Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr
485 490 495
Lys Leu Thr Val Leu
500
<210> 125
<211> 492
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 125
Glu Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Leu Ser Cys Thr Ala Ser Gly Phe Asn Ile Asn Asp Thr
20 25 30
Tyr Met His Trp Val Lys Gln Arg Pro Glu Gln Gly Leu Glu Trp Ile
35 40 45
Gly Arg Ile Asp Pro Ala Asn Gly Asn Thr Lys Tyr Asp Pro Lys Phe
50 55 60
Gln Gly Lys Ala Thr Ile Thr Ala Asp Thr Ser Ser Asn Thr Ala Tyr
65 70 75 80
Leu Gln Leu Ser Ser Leu Thr Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Gly Ala Arg Gly Ser Arg Phe Ala Tyr Trp Gly Gln Gly Thr
100 105 110
Leu Val Thr Val Ser Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
115 120 125
Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ala Ser Leu
130 135 140
Ser Val Ser Val Gly Glu Thr Val Thr Ile Thr Cys Arg Ala Ser Glu
145 150 155 160
Asn Ile Tyr Ser Asn Leu Ala Trp Tyr Gln Gln Lys Gln Gly Lys Ser
165 170 175
Pro Gln Leu Leu Val Tyr Val Ala Thr Asn Leu Ala Asp Gly Val Pro
180 185 190
Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Gln Tyr Ser Leu Lys Ile
195 200 205
Asn Ser Leu Gln Ser Glu Asp Phe Gly Ser Tyr Tyr Cys Gln His Phe
210 215 220
Trp Gly Thr Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Ser Gly Gly
225 230 235 240
Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln
245 250 255
Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe
260 265 270
Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
275 280 285
Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr
290 295 300
Tyr Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser
305 310 315 320
Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr
325 330 335
Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile
340 345 350
Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
355 360 365
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln
370 375 380
Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr
385 390 395 400
Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn
405 410 415
Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu
420 425 430
Ile Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser
435 440 445
Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln
450 455 460
Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg
465 470 475 480
Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
485 490
<210> 126
<211> 499
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 126
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Gln
1 5 10 15
Ser Leu Lys Ile Ser Cys Lys Ala Ser Gly Tyr Ser Leu Thr Asp Asn
20 25 30
Trp Ile Gly Trp Val Arg Gln Lys Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Ile Ile Tyr Pro Gly Asp Ser Asp Thr Arg Tyr Ser Pro Ser Phe
50 55 60
Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Asn Thr Ala Tyr
65 70 75 80
Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Val Gly Leu Asp Trp Asn Tyr Asn Pro Leu Arg Tyr Trp Gly Pro Gly
100 105 110
Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
115 120 125
Ser Gly Gly Gly Gly Ser Gln Ser Val Leu Thr Gln Pro Pro Ser Val
130 135 140
Ser Ala Ala Pro Gly Gln Lys Val Thr Ile Ser Cys Ser Gly Ser Ser
145 150 155 160
Ser Asp Ile Gly Ser Asn Tyr Val Ser Trp Tyr Gln Gln Phe Pro Gly
165 170 175
Thr Ala Pro Lys Leu Leu Ile Tyr Asp Asn Asn Lys Arg Pro Ser Ala
180 185 190
Ile Pro Asp Arg Phe Ser Gly Ser Lys Ser Gly Thr Ser Ala Thr Leu
195 200 205
Gly Ile Thr Gly Leu Gln Thr Gly Asp Glu Ala Asp Tyr Tyr Cys Gly
210 215 220
Thr Trp Asp Ser Arg Leu Gly Ile Ala Val Phe Gly Gly Gly Thr Gln
225 230 235 240
Leu Thr Val Leu Ser Gly Gly Gly Gly Ser Glu Val Gln Leu Val Glu
245 250 255
Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys
260 265 270
Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg
275 280 285
Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys
290 295 300
Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys Asp Arg Phe
305 310 315 320
Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn
325 330 335
Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly
340 345 350
Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly
355 360 365
Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
370 375 380
Ser Gly Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu
385 390 395 400
Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr
405 410 415
Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro
420 425 430
Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu Ala Pro
435 440 445
Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala
450 455 460
Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys
465 470 475 480
Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu
485 490 495
Thr Val Leu
<210> 127
<211> 507
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 127
Glu Val Gln Leu Val Glu Ser Gly Gly Asp Leu Val Lys Pro Gly Gly
1 5 10 15
Ser Leu Lys Leu Ser Cys Ala Val Ser Gly Phe Thr Phe Ser Ser Tyr
20 25 30
Gly Met Ser Trp Val Arg Gln Thr Pro Asp Lys Arg Leu Glu Trp Val
35 40 45
Ala Thr Val Ser Ser Gly Gly Thr Tyr Thr Tyr Tyr Pro Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Ser Ser Leu Lys Ser Glu Asp Ser Ala Met Tyr Tyr Cys
85 90 95
Ala Arg His Arg Gly Asn Tyr Tyr Ala Thr Tyr Tyr Tyr Ala Met Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Ser Val Thr Val Ser Ser Gly Gly Gly Gly
115 120 125
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Val Leu Thr
130 135 140
Gln Ser Pro Ala Ser Leu Ala Val Ser Leu Gly Gln Gly Ala Thr Ile
145 150 155 160
Ser Cys Arg Ala Ser Lys Ser Val Ser Thr Ser Gly Tyr Thr Tyr Met
165 170 175
His Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr
180 185 190
Leu Ala Ser Asn Leu Glu Ser Gly Val Pro Ala Arg Phe Ser Gly Ser
195 200 205
Gly Ser Gly Thr Asp Phe Thr Leu Asn Ile His Pro Val Glu Glu Glu
210 215 220
Asp Ala Ala Thr Tyr Tyr Cys Gln His Ser Gly Glu Leu Pro Pro Ser
225 230 235 240
Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Ala Ser Gly Gly Gly
245 250 255
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
260 265 270
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
275 280 285
Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
290 295 300
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
305 310 315 320
Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
325 330 335
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
340 345 350
Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser
355 360 365
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr
385 390 395 400
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
405 410 415
Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
420 425 430
Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
435 440 445
Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly
450 455 460
Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
465 470 475 480
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
485 490 495
Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
500 505
<210> 128
<211> 498
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 128
Gln Val Gln Leu Gln Gln Pro Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Lys Leu Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Thr Tyr
20 25 30
Trp Met Asn Trp Val Lys Gln Arg Pro Glu Gln Gly Leu Glu Trp Ile
35 40 45
Gly Arg Ile Asp Pro Tyr Asp Ser Glu Thr His Tyr Asn Gln Lys Phe
50 55 60
Lys Asp Lys Ala Ile Leu Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Gly Pro Tyr Tyr Gly Thr Asn Pro Trp Phe Pro Tyr Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly
115 120 125
Gly Gly Ser Gly Gly Gly Gly Ser Asp Val Gln Ile Thr Gln Ser Pro
130 135 140
Ser Tyr Leu Ala Ala Ser Pro Gly Glu Thr Ile Thr Ile Asn Cys Arg
145 150 155 160
Ala Ser Lys Ser Ile Ser Lys Tyr Leu Ala Trp Tyr Gln Glu Lys Pro
165 170 175
Gly Lys Thr Asn Lys Leu Leu Ile Tyr Ser Gly Ser Thr Leu Gln Ser
180 185 190
Gly Ile Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr
195 200 205
Leu Thr Ile Ser Ser Leu Glu Pro Glu Asp Phe Ala Met Tyr Tyr Cys
210 215 220
Gln Gln His His Glu Tyr Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu
225 230 235 240
Glu Ile Lys Ser Gly Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser
245 250 255
Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala
260 265 270
Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln
275 280 285
Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr
290 295 300
Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys Asp Arg Phe Thr
305 310 315 320
Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn
325 330 335
Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn
340 345 350
Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr
355 360 365
Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
370 375 380
Gly Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr
385 390 395 400
Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly
405 410 415
Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly
420 425 430
Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu Ala Pro Gly
435 440 445
Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu
450 455 460
Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val
465 470 475 480
Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr
485 490 495
Val Leu
<210> 129
<211> 496
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 129
Gln Val Gln Leu Gln Gln Trp Gly Ala Gly Leu Leu Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Ala Val Phe Gly Gly Ser Phe Ser Gly Tyr
20 25 30
Tyr Trp Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Glu Ile Asn His Arg Gly Asn Thr Asn Asp Asn Pro Ser Leu Lys
50 55 60
Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ala Leu
65 70 75 80
Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala
85 90 95
Arg Glu Arg Gly Tyr Thr Tyr Gly Asn Phe Asp His Trp Gly Gln Gly
100 105 110
Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
115 120 125
Ser Gly Gly Gly Gly Ser Glu Ile Val Met Thr Gln Ser Pro Ala Thr
130 135 140
Leu Ser Val Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser
145 150 155 160
Gln Ser Val Ser Arg Asn Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
165 170 175
Ala Pro Arg Leu Leu Ile Tyr Gly Ala Ser Thr Arg Ala Thr Gly Ile
180 185 190
Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr
195 200 205
Ile Gly Ser Leu Gln Ser Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln
210 215 220
Tyr Lys Thr Trp Pro Arg Thr Phe Gly Gln Gly Thr Asn Val Glu Ile
225 230 235 240
Lys Ser Gly Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly
245 250 255
Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser
260 265 270
Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro
275 280 285
Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn
290 295 300
Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser
305 310 315 320
Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys
325 330 335
Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly
340 345 350
Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val
355 360 365
Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
370 375 380
Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser
385 390 395 400
Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val
405 410 415
Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala
420 425 430
Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro
435 440 445
Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu
450 455 460
Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp
465 470 475 480
Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
485 490 495
<210> 130
<211> 501
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 130
Gln Val Gln Leu Arg Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Val Ile Ser Trp Val Lys Gln Arg Thr Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Asp Ile Tyr Pro Gly Ser Gly Tyr Ser Phe Tyr Asn Glu Asn Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Ala Asp Lys Ser Ser Thr Thr Ala Tyr
65 70 75 80
Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Phe Cys
85 90 95
Ala Thr Tyr Tyr Asn Tyr Pro Phe Ala Tyr Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
115 120 125
Gly Gly Gly Ser Asp Val Val Met Thr Gln Thr Pro Leu Ser Leu Pro
130 135 140
Val Arg Leu Gly Asp Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser
145 150 155 160
Leu Val His Ser Asn Gly Asn Thr Tyr Leu His Trp Tyr Leu Gln Lys
165 170 175
Pro Gly Gln Ser Pro Lys Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe
180 185 190
Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asn Phe
195 200 205
Thr Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Leu Gly Leu Tyr Phe
210 215 220
Cys Ser Gln Ser Thr His Val Pro Tyr Thr Phe Gly Gly Gly Thr Lys
225 230 235 240
Leu Glu Ile Lys Arg Ala Ser Gly Gly Gly Gly Ser Glu Val Gln Leu
245 250 255
Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu
260 265 270
Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp
275 280 285
Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg
290 295 300
Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys Asp
305 310 315 320
Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln
325 330 335
Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg
340 345 350
His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly
355 360 365
Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly
370 375 380
Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro
385 390 395 400
Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser
405 410 415
Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln
420 425 430
Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu
435 440 445
Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys
450 455 460
Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr
465 470 475 480
Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr
485 490 495
Lys Leu Thr Val Leu
500
<210> 131
<211> 501
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 131
Gln Val Gln Leu Gln Gln Pro Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Lys Leu Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Trp Ile Asn Trp Val Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Asn Ile Tyr Pro Ser Asp Ser Tyr Thr Asn Tyr Asn Gln Lys Phe
50 55 60
Lys Asp Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Gln Leu Ser Ser Pro Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Ser Trp Arg Gly Asn Ser Phe Asp Tyr Trp Gly Gln Gly Thr
100 105 110
Thr Leu Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
115 120 125
Gly Gly Gly Gly Ser Asp Ile Val Met Thr Gln Ser Pro Ser Ser Leu
130 135 140
Thr Val Thr Ala Gly Glu Lys Val Thr Met Ser Cys Lys Ser Ser Gln
145 150 155 160
Ser Leu Leu Asn Ser Gly Asn Gln Lys Asn Tyr Leu Thr Trp Tyr Gln
165 170 175
Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr
180 185 190
Arg Glu Ser Gly Val Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr
195 200 205
Asp Phe Thr Leu Thr Ile Ser Ser Val Gln Ala Glu Asp Leu Ala Val
210 215 220
Tyr Tyr Cys Gln Asn Asp Tyr Ser Tyr Pro Phe Thr Phe Gly Ser Gly
225 230 235 240
Thr Lys Leu Glu Ile Lys Ser Gly Gly Gly Gly Ser Glu Val Gln Leu
245 250 255
Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu
260 265 270
Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp
275 280 285
Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg
290 295 300
Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys Asp
305 310 315 320
Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln
325 330 335
Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg
340 345 350
His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly
355 360 365
Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly
370 375 380
Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro
385 390 395 400
Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser
405 410 415
Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln
420 425 430
Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu
435 440 445
Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys
450 455 460
Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr
465 470 475 480
Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr
485 490 495
Lys Leu Thr Val Leu
500
<210> 132
<211> 496
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 132
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Gly
1 5 10 15
Ser Met Lys Ile Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr
20 25 30
Thr Met Asn Trp Val Lys Gln Ser His Gly Lys Asn Leu Glu Trp Ile
35 40 45
Gly Leu Ile Asn Pro Tyr Asn Gly Gly Ile Ser Tyr Asn Gln Lys Phe
50 55 60
Lys Asp Lys Ala Thr Leu Thr Met Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Leu Ser Leu Thr Ser Glu Asp Ser Ala Ile Tyr Phe Cys
85 90 95
Ala Arg Asp Tyr Arg Tyr Glu Gly Phe Asp Tyr Trp Gly Gln Gly Thr
100 105 110
Leu Val Thr Val Ser Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
115 120 125
Gly Gly Gly Gly Ser Gln Ile Val Leu Thr Gln Ser Pro Ala Ile Met
130 135 140
Ser Ala Ser Leu Gly Glu Arg Val Thr Met Thr Cys Thr Ala Ser Ser
145 150 155 160
Val Val Ile Ser Thr Tyr Leu His Trp Tyr Gln Gln Lys Pro Gly Ser
165 170 175
Ser Pro Lys Leu Trp Ile Tyr Ser Thr Ser Asn Leu Ala Ser Gly Val
180 185 190
Pro Val Arg Phe Ser Gly Ser Gly Ser Gly Thr Ser Tyr Ser Leu Thr
195 200 205
Ile Ser Ser Met Glu Ala Glu Asp Ala Ala Thr Tyr Tyr Cys His Gln
210 215 220
Tyr His Arg Ser Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile
225 230 235 240
Lys Ser Gly Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly
245 250 255
Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser
260 265 270
Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro
275 280 285
Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn
290 295 300
Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser
305 310 315 320
Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys
325 330 335
Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly
340 345 350
Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val
355 360 365
Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
370 375 380
Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser
385 390 395 400
Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val
405 410 415
Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala
420 425 430
Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro
435 440 445
Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu
450 455 460
Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp
465 470 475 480
Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
485 490 495
<210> 133
<211> 505
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 133
Glu Ile Gln Leu Gln Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Asp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Thr Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Ser Phe Tyr Tyr Thr Tyr Ser Asn Tyr Asp Val Gly Phe Ala Tyr
100 105 110
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser
115 120 125
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Val Met Thr Gln
130 135 140
Ser Pro Leu Ser Leu Pro Val Thr Pro Gly Glu Pro Ala Ser Ile Ser
145 150 155 160
Cys Arg Ser Thr Lys Ser Leu Leu His Ser Asn Gly Asn Thr Tyr Leu
165 170 175
Tyr Trp Tyr Leu Gln Lys Pro Gly Gln Ser Pro Gln Leu Leu Ile Tyr
180 185 190
Arg Met Ser Asn Leu Ala Ser Gly Val Pro Asp Arg Phe Ser Gly Ser
195 200 205
Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile Ser Arg Val Glu Ala Glu
210 215 220
Asp Val Gly Val Tyr Tyr Cys Met Gln His Leu Glu Tyr Pro Phe Thr
225 230 235 240
Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Ser Gly Gly Gly Gly Ser
245 250 255
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
260 265 270
Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr
275 280 285
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
290 295 300
Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp
305 310 315 320
Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr
325 330 335
Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr
340 345 350
Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp
355 360 365
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly
370 375 380
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val Val
385 390 395 400
Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu
405 410 415
Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn
420 425 430
Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly
435 440 445
Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu
450 455 460
Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp
465 470 475 480
Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe
485 490 495
Gly Gly Gly Thr Lys Leu Thr Val Leu
500 505
<210> 134
<211> 493
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 134
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser Ile Thr Asn Asp
20 25 30
Tyr Ala Trp Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
35 40 45
Val Gly Tyr Ile Ser Tyr Ser Gly Tyr Thr Thr Tyr Asn Pro Ser Leu
50 55 60
Lys Ser Arg Phe Thr Ile Ser Arg Asp Thr Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Trp Thr Ser Gly Leu Asp Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
115 120 125
Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala
130 135 140
Ser Val Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Asp Leu Ile
145 150 155 160
His Asn Trp Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys
165 170 175
Leu Leu Ile Tyr Gly Ala Thr Ser Leu Glu Thr Gly Val Pro Ser Arg
180 185 190
Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser
195 200 205
Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Trp Thr
210 215 220
Thr Pro Phe Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Ser Gly
225 230 235 240
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
245 250 255
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
260 265 270
Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
275 280 285
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
290 295 300
Tyr Tyr Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
305 310 315 320
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
325 330 335
Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr
340 345 350
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
355 360 365
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
370 375 380
Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly
385 390 395 400
Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly
405 410 415
Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly
420 425 430
Leu Ile Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe
435 440 445
Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val
450 455 460
Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn
465 470 475 480
Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
485 490
<210> 135
<211> 109
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 135
Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly
1 5 10 15
Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly
20 25 30
Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly
35 40 45
Leu Ile Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe
50 55 60
Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val
65 70 75 80
Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn
85 90 95
Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
100 105
<210> 136
<211> 244
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 136
Gln Ser Val Leu Thr Gln Pro Pro Ser Val Ser Ala Ala Pro Gly Gln
1 5 10 15
Lys Val Thr Ile Ser Cys Ser Gly Ser Ser Ser Asp Ile Gly Ser Asn
20 25 30
Tyr Val Ser Trp Tyr Gln Gln Phe Pro Gly Thr Ala Pro Lys Leu Leu
35 40 45
Ile Tyr Asp Asn Asn Lys Arg Pro Ser Ala Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Lys Ser Gly Thr Ser Ala Thr Leu Gly Ile Thr Gly Leu Gln
65 70 75 80
Thr Gly Asp Glu Ala Asp Tyr Tyr Cys Gly Thr Trp Asp Ser Arg Leu
85 90 95
Gly Ile Ala Val Phe Gly Gly Gly Thr Gln Leu Thr Val Leu Gly Gly
100 105 110
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Gln
115 120 125
Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Gln Ser Leu Lys
130 135 140
Ile Ser Cys Lys Ala Ser Gly Tyr Ser Leu Thr Asp Asn Trp Ile Gly
145 150 155 160
Trp Val Arg Gln Lys Pro Gly Lys Gly Leu Glu Trp Met Gly Ile Ile
165 170 175
Tyr Pro Gly Asp Ser Asp Thr Arg Tyr Ser Pro Ser Phe Gln Gly Gln
180 185 190
Val Thr Ile Ser Ala Asp Lys Ser Ile Asn Thr Ala Tyr Leu Gln Trp
195 200 205
Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile Tyr Tyr Cys Val Gly Leu
210 215 220
Asp Trp Asn Tyr Asn Pro Leu Arg Tyr Trp Gly Pro Gly Thr Leu Val
225 230 235 240
Thr Val Ser Ser
<210> 137
<211> 252
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 137
Asp Ile Val Leu Thr Gln Ser Pro Ala Ser Leu Ala Val Ser Leu Gly
1 5 10 15
Gln Gly Ala Thr Ile Ser Cys Arg Ala Ser Lys Ser Val Ser Thr Ser
20 25 30
Gly Tyr Thr Tyr Met His Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro
35 40 45
Lys Leu Leu Ile Tyr Leu Ala Ser Asn Leu Glu Ser Gly Val Pro Ala
50 55 60
Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Asn Ile His
65 70 75 80
Pro Val Glu Glu Glu Asp Ala Ala Thr Tyr Tyr Cys Gln His Ser Gly
85 90 95
Glu Leu Pro Pro Ser Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg
100 105 110
Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
115 120 125
Glu Val Gln Leu Val Glu Ser Gly Gly Asp Leu Val Lys Pro Gly Gly
130 135 140
Ser Leu Lys Leu Ser Cys Ala Val Ser Gly Phe Thr Phe Ser Ser Tyr
145 150 155 160
Gly Met Ser Trp Val Arg Gln Thr Pro Asp Lys Arg Leu Glu Trp Val
165 170 175
Ala Thr Val Ser Ser Gly Gly Thr Tyr Thr Tyr Tyr Pro Asp Ser Val
180 185 190
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr
195 200 205
Leu Gln Met Ser Ser Leu Lys Ser Glu Asp Ser Ala Met Tyr Tyr Cys
210 215 220
Ala Arg His Arg Gly Asn Tyr Tyr Ala Thr Tyr Tyr Tyr Ala Met Asp
225 230 235 240
Tyr Trp Gly Gln Gly Thr Ser Val Thr Val Ser Ser
245 250
<210> 138
<211> 243
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 138
Asp Val Gln Ile Thr Gln Ser Pro Ser Tyr Leu Ala Ala Ser Pro Gly
1 5 10 15
Glu Thr Ile Thr Ile Asn Cys Arg Ala Ser Lys Ser Ile Ser Lys Tyr
20 25 30
Leu Ala Trp Tyr Gln Glu Lys Pro Gly Lys Thr Asn Lys Leu Leu Ile
35 40 45
Tyr Ser Gly Ser Thr Leu Gln Ser Gly Ile Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro
65 70 75 80
Glu Asp Phe Ala Met Tyr Tyr Cys Gln Gln His His Glu Tyr Pro Tyr
85 90 95
Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser
100 105 110
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Gln
115 120 125
Pro Gly Ala Glu Leu Val Arg Pro Gly Ala Ser Val Lys Leu Ser Cys
130 135 140
Lys Ala Ser Gly Tyr Thr Phe Thr Thr Tyr Trp Met Asn Trp Val Lys
145 150 155 160
Gln Arg Pro Glu Gln Gly Leu Glu Trp Ile Gly Arg Ile Asp Pro Tyr
165 170 175
Asp Ser Glu Thr His Tyr Asn Gln Lys Phe Lys Asp Lys Ala Ile Leu
180 185 190
Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr Met Gln Leu Ser Ser Leu
195 200 205
Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys Ala Arg Gly Pro Tyr Tyr
210 215 220
Gly Thr Asn Pro Trp Phe Pro Tyr Trp Gly Gln Gly Thr Leu Val Thr
225 230 235 240
Val Ser Ser
<210> 139
<211> 241
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 139
Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Val Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Arg Asn
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile
35 40 45
Tyr Gly Ala Ser Thr Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Gly Ser Leu Gln Ser
65 70 75 80
Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Lys Thr Trp Pro Arg
85 90 95
Thr Phe Gly Gln Gly Thr Asn Val Glu Ile Lys Gly Gly Gly Gly Ser
100 105 110
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Gln
115 120 125
Trp Gly Ala Gly Leu Leu Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys
130 135 140
Ala Val Phe Gly Gly Ser Phe Ser Gly Tyr Tyr Trp Ser Trp Ile Arg
145 150 155 160
Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Glu Ile Asn His Arg
165 170 175
Gly Asn Thr Asn Asp Asn Pro Ser Leu Lys Ser Arg Val Thr Ile Ser
180 185 190
Val Asp Thr Ser Lys Asn Gln Phe Ala Leu Lys Leu Ser Ser Val Thr
195 200 205
Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg Glu Arg Gly Tyr Thr
210 215 220
Tyr Gly Asn Phe Asp His Trp Gly Gln Gly Thr Leu Val Thr Val Ser
225 230 235 240
Ser
<210> 140
<211> 246
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 140
Asp Val Val Met Thr Gln Thr Pro Leu Ser Leu Pro Val Arg Leu Gly
1 5 10 15
Asp Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Gly Asn Thr Tyr Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser
35 40 45
Pro Lys Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asn Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Leu Gly Leu Tyr Phe Cys Ser Gln Ser
85 90 95
Thr His Val Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
115 120 125
Ser Gln Val Gln Leu Arg Gln Ser Gly Pro Glu Leu Val Lys Pro Gly
130 135 140
Ala Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp
145 150 155 160
Tyr Val Ile Ser Trp Val Lys Gln Arg Thr Gly Gln Gly Leu Glu Trp
165 170 175
Ile Gly Asp Ile Tyr Pro Gly Ser Gly Tyr Ser Phe Tyr Asn Glu Asn
180 185 190
Phe Lys Gly Lys Ala Thr Leu Thr Ala Asp Lys Ser Ser Thr Thr Ala
195 200 205
Tyr Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Phe
210 215 220
Cys Ala Thr Tyr Tyr Asn Tyr Pro Phe Ala Tyr Trp Gly Gln Gly Thr
225 230 235 240
Leu Val Thr Val Ser Ala
245
<210> 141
<211> 199
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 141
Leu Pro Ile Cys Pro Gly Gly Ala Ala Arg Cys Gln Val Thr Leu Arg
1 5 10 15
Asp Leu Phe Asp Arg Ala Val Val Leu Ser His Tyr Ile His Asn Leu
20 25 30
Ser Ser Glu Met Phe Ser Glu Phe Asp Lys Arg Tyr Thr His Gly Arg
35 40 45
Gly Phe Ile Thr Lys Ala Ile Asn Ser Cys His Thr Ser Ser Leu Ala
50 55 60
Thr Pro Glu Asp Lys Glu Gln Ala Gln Gln Met Asn Gln Lys Asp Phe
65 70 75 80
Leu Ser Leu Ile Val Ser Ile Leu Arg Ser Trp Asn Glu Pro Leu Tyr
85 90 95
His Leu Val Thr Glu Val Arg Gly Met Gln Glu Ala Pro Glu Ala Ile
100 105 110
Leu Ser Lys Ala Val Glu Ile Glu Glu Gln Thr Lys Arg Leu Leu Glu
115 120 125
Gly Met Glu Leu Ile Val Ser Gln Val His Pro Glu Thr Lys Glu Asn
130 135 140
Glu Ile Tyr Pro Val Trp Ser Gly Leu Pro Ser Leu Gln Met Ala Asp
145 150 155 160
Glu Glu Ser Arg Leu Ser Ala Tyr Tyr Asn Leu Leu His Cys Leu Arg
165 170 175
Arg Asp Ser His Lys Ile Asp Asn Tyr Leu Lys Leu Leu Lys Cys Arg
180 185 190
Ile Ile His Asn Asn Asn Cys
195
<210> 142
<211> 240
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 142
Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly
1 5 10 15
Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Leu Leu Asn Ser
20 25 30
Arg Thr Arg Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
35 40 45
Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val
50 55 60
Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
65 70 75 80
Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Thr Gln
85 90 95
Ser Phe Ile Leu Arg Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105 110
Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
115 120 125
Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly
130 135 140
Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Leu Leu Asn Ser
145 150 155 160
Arg Thr Arg Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
165 170 175
Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val
180 185 190
Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
195 200 205
Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Thr Gln
210 215 220
Ser Phe Ile Leu Arg Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
225 230 235 240
<210> 143
<211> 281
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 143
Met Asn Val Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp Leu Thr
1 5 10 15
Gly Gly Lys Cys Asp Ile Gln Met Thr Gln Ser Pro Ala Ser Leu Ser
20 25 30
Ala Ser Leu Glu Glu Ile Val Thr Ile Thr Cys Lys Ala Ser Gln Ala
35 40 45
Ile Asp Ala Tyr Leu Ser Trp Tyr Gln Gln Lys Pro Gly Lys Ser Pro
50 55 60
Gln Leu Leu Ile Tyr Asp Ala Thr Ser Leu Ala Asp Gly Val Pro Ser
65 70 75 80
Arg Phe Ser Gly Ser Arg Ser Gly Thr Gln Tyr Ser Leu Lys Ile Ser
85 90 95
Arg Pro Gln Val Asp Asp Ser Gly Ile Tyr Tyr Cys Leu Gln Ser Tyr
100 105 110
Ser Thr Pro Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Gly
115 120 125
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Met
130 135 140
Ala Val Leu Val Leu Leu Leu Cys Leu Leu Ile Phe Pro Ser Cys Val
145 150 155 160
Leu Ser Gln Val Gln Leu Lys Glu Ser Gly Pro Gly Leu Val Gln Pro
165 170 175
Ser Gln Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Ser Ser Leu Thr
180 185 190
Ser Asn Ser Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu
195 200 205
Trp Met Gly Val Ile Trp Ser Asn Gly Asp Ala Asp Tyr Asn Ser Ala
210 215 220
Ile Lys Ser Arg Leu Ser Ile Ser Arg Asp Thr Ser Lys Ser Gln Val
225 230 235 240
Phe Leu Lys Met Asn Ser Leu Gln Thr Glu Asp Thr Ala Met Tyr Phe
245 250 255
Cys Ala Ser Pro Tyr Tyr Gly Tyr Tyr Phe Pro Phe Asp Tyr Trp Gly
260 265 270
Gln Gly Val Met Val Thr Val Ser Ser
275 280
<210> 144
<211> 285
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 144
Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro
1 5 10 15
Gly Ser Thr Gly Asp Ile Val Leu Thr Gln Ser Pro Ala Leu Ala Val
20 25 30
Ser Leu Gly Gln Arg Ala Thr Ile Ser Cys Arg Ala Ser Gln Ser Val
35 40 45
Ser Ile Ser Ser His Asp Leu Met Gln Trp Tyr Gln Gln Lys Pro Gly
50 55 60
Gln Gln Pro Lys Leu Leu Ile Tyr Asp Ala Phe Asn Leu Ala Ser Gly
65 70 75 80
Ile Pro Val Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu
85 90 95
Thr Ile Asp Pro Val Gln Ala Asp Asp Ile Ala Thr Tyr Tyr Cys Gln
100 105 110
Gln Ser Lys Asp Asp Pro Tyr Thr Phe Gly Ala Gly Thr Lys Leu Glu
115 120 125
Leu Lys Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly
130 135 140
Gly Ser Met Asp Ile Arg Leu Ser Leu Ala Phe Leu Val Leu Phe Ile
145 150 155 160
Lys Gly Val Gln Cys Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu
165 170 175
Val Gln Pro Gly Arg Ser Met Lys Leu Ser Cys Ala Ala Ser Gly Phe
180 185 190
Thr Phe Ser Asn Tyr Gly Met Ala Trp Val Arg Gln Ala Pro Thr Lys
195 200 205
Gly Leu Glu Trp Val Ala Thr Ile Ser Tyr Asp Gly Ser Ile Thr Tyr
210 215 220
Tyr Arg Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp His Ala
225 230 235 240
Lys Ser Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ser Glu Asp Thr
245 250 255
Ala Thr Tyr Tyr Cys Thr Arg Glu Glu Gln Tyr Ser Ser Trp Tyr Phe
260 265 270
Asp Phe Trp Gly Pro Gly Ile Met Val Thr Val Ser Ser
275 280 285
<210> 145
<211> 242
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 145
Asn Ile Val Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Val Gly Thr Ala
20 25 30
Val Ala Trp Tyr Gln Gln Lys Pro Asp Gln Ser Pro Lys Leu Leu Ile
35 40 45
Tyr Trp Thr Ser Thr Arg His Thr Gly Val Pro Asp Arg Phe Thr Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Ile Ala Thr Tyr Phe Cys His Gln Tyr Asn Ser Tyr Asn Thr
85 90 95
Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Gly Ser
100 105 110
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Thr Leu Lys Glu
115 120 125
Ser Gly Pro Val Leu Val Lys Pro Thr Glu Thr Leu Thr Leu Thr Cys
130 135 140
Thr Phe Ser Gly Phe Ser Leu Ser Thr Ser Gly Met Gly Val Gly Trp
145 150 155 160
Ile Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala His Ile Trp
165 170 175
Trp Asp Asp Asp Val Tyr Tyr Asn Pro Ser Leu Lys Ser Arg Leu Thr
180 185 190
Ile Thr Lys Asp Ala Ser Lys Asp Gln Val Ser Leu Lys Leu Ser Ser
195 200 205
Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Val Arg Arg Arg Ala
210 215 220
Thr Gly Thr Gly Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val
225 230 235 240
Ser Ser
<210> 146
<211> 246
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 146
Glu Ile Val Leu Thr Gln Ser Pro Gly Ser Leu Ala Val Ser Pro Gly
1 5 10 15
Glu Arg Val Thr Met Ser Cys Lys Ser Ser Gln Ser Val Phe Phe Ser
20 25 30
Ser Ser Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Ile Pro Gly Gln
35 40 45
Ser Pro Arg Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val
50 55 60
Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
65 70 75 80
Ile Ser Ser Val Gln Pro Glu Asp Leu Ala Ile Tyr Tyr Cys His Gln
85 90 95
Tyr Leu Ser Ser Arg Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
115 120 125
Gln Val Gln Leu Gln Gln Pro Gly Ala Glu Val Val Lys Pro Gly Ala
130 135 140
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
145 150 155 160
Tyr Ile His Trp Ile Lys Gln Thr Pro Gly Gln Gly Leu Glu Trp Val
165 170 175
Gly Val Ile Tyr Pro Gly Asn Asp Asp Ile Ser Tyr Asn Gln Lys Phe
180 185 190
Gln Gly Lys Ala Thr Leu Thr Ala Asp Lys Ser Ser Thr Thr Ala Tyr
195 200 205
Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
210 215 220
Ala Arg Glu Val Arg Leu Arg Tyr Phe Asp Val Trp Gly Gln Gly Thr
225 230 235 240
Thr Val Thr Val Ser Ser
245
<210> 147
<211> 255
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 147
Met Ala Asp Tyr Lys Asp Ile Val Met Thr Gln Ser Pro Ser Ser Val
1 5 10 15
Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln
20 25 30
Asn Val Asp Ser Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala
35 40 45
Pro Lys Ala Leu Ile Tyr Ser Ala Ser Tyr Arg Tyr Ser Gly Val Pro
50 55 60
Ser Arg Phe Ser Gly Arg Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile
65 70 75 80
Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr
85 90 95
Tyr Ser Thr Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105 110
Arg Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
115 120 125
Glu Val Lys Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg
130 135 140
Ser Leu Arg Leu Ser Cys Thr Ala Ser Gly Phe Thr Phe Thr Asp Tyr
145 150 155 160
Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
165 170 175
Gly Leu Ile Arg Ser Lys Ala Asp Gly Tyr Thr Thr Glu Tyr Ser Ala
180 185 190
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Ser Ile
195 200 205
Leu Tyr Leu Gln Met Asn Ser Leu Lys Thr Glu Asp Thr Ala Val Tyr
210 215 220
Tyr Cys Ala Arg Asp Ala Ala Tyr Tyr Ser Tyr Tyr Ser Pro Glu Gly
225 230 235 240
Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
245 250 255
<210> 148
<211> 244
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 148
Gln Ser Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln
1 5 10 15
Arg Val Thr Ile Ser Cys Ser Gly Ser Ser Ser Asn Ile Gly Ile Asn
20 25 30
Thr Val Asn Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu Leu
35 40 45
Ile Tyr Asp Asn Asn Lys Arg Pro Ser Gly Val Pro Asp Arg Phe Ser
50 55 60
Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Arg
65 70 75 80
Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Thr Trp Asp Asp Ser Leu
85 90 95
Ser Gly Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly
100 105 110
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Gln
115 120 125
Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg
130 135 140
Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asp Tyr Tyr Met Ser
145 150 155 160
Trp Ile Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ala Ile
165 170 175
Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg
180 185 190
Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met
195 200 205
Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Lys Glu
210 215 220
Asp Trp Glu Gly Ala Ser Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val
225 230 235 240
Thr Val Ser Ser
<210> 149
<211> 245
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 149
Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly
1 5 10 15
Glu Arg Ala Thr Ile Asn Cys Arg Ala Ser Lys Ser Val Ser Thr Ser
20 25 30
Gly Tyr Ser Phe Met His Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro
35 40 45
Lys Leu Leu Ile Tyr Leu Ala Ser Asn Leu Glu Ser Gly Val Pro Asp
50 55 60
Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser
65 70 75 80
Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln His Ser Arg
85 90 95
Glu Val Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg
100 105 110
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln
115 120 125
Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser
130 135 140
Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr Gly
145 150 155 160
Met Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly
165 170 175
Trp Ile Asn Thr Tyr Thr Gly Glu Pro Thr Tyr Ala Asp Ala Phe Lys
180 185 190
Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr Met
195 200 205
Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala
210 215 220
Arg Asp Tyr Gly Asp Tyr Gly Met Asp Tyr Trp Gly Gln Gly Thr Thr
225 230 235 240
Val Thr Val Ser Ser
245
<210> 150
<211> 263
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 150
Ala Gln Ala Ala Glu Leu Asp Ile Val Leu Ser Gln Ser Pro Ala Ile
1 5 10 15
Met Ser Ala Ser Pro Gly Glu Lys Val Thr Ile Ser Cys Ser Ala Ser
20 25 30
Ser Ser Val Ser Tyr Met Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Ser
35 40 45
Pro Lys Pro Trp Ile Tyr Arg Thr Ser Asn Leu Ala Ser Gly Val Pro
50 55 60
Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile
65 70 75 80
Ser Ser Met Glu Ala Glu Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Tyr
85 90 95
His Ser Tyr Pro Pro Thr Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys
100 105 110
Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Gly Gly Ser Ser Arg
115 120 125
Ser Ser Leu Glu Val Lys Leu Val Glu Ser Gly Pro Glu Leu Lys Lys
130 135 140
Pro Gly Glu Thr Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe
145 150 155 160
Thr Asp Tyr Ser Met His Trp Val Asn Gln Ala Pro Gly Lys Gly Leu
165 170 175
Lys Trp Met Gly Trp Ile Asn Thr Glu Thr Gly Glu Pro Ser Tyr Ala
180 185 190
Asp Asp Phe Lys Gly Arg Phe Ala Phe Ser Leu Glu Thr Ser Ala Ser
195 200 205
Thr Ala Tyr Leu Gln Ile Asn Asn Leu Lys Asn Glu Asp Thr Ala Thr
210 215 220
Tyr Phe Cys Ala Thr Asp Tyr Gly Asp Tyr Phe Asp Tyr Trp Gly Gln
225 230 235 240
Gly Thr Thr Leu Thr Val Ser Ser Ala Lys Thr Thr Pro Pro Ser Val
245 250 255
Thr Ser Gly Gln Ala Gly Gln
260
<210> 151
<211> 239
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 151
Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr
20 25 30
Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Thr Ile Gln Lys Gln Gly Leu Pro Thr Glu Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Lys Asn Arg Ala Lys Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
115 120 125
Gly Gly Ser Thr Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser
130 135 140
Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser
145 150 155 160
Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro
165 170 175
Lys Leu Leu Ile Tyr Asn Ala Ser Met Leu Gln Ser Gly Val Pro Ser
180 185 190
Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser
195 200 205
Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Asn Arg
210 215 220
Gly Phe Pro Leu Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
225 230 235
<210> 152
<211> 239
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 152
Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Val Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Asn
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Ile Ile
35 40 45
Tyr Gly Ala Ser Thr Thr Ala Ser Gly Ile Pro Ala Arg Phe Ser Ala
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ser
65 70 75 80
Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asn Asn Trp Pro Pro
85 90 95
Ala Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly
100 105 110
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu
115 120 125
Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser Ser Val Lys Val
130 135 140
Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr Ala Ile Ser Trp
145 150 155 160
Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Gly Ile Ile
165 170 175
Pro Ile Phe Gly Thr Ala Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val
180 185 190
Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr Met Glu Leu Ser
195 200 205
Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Gly Leu
210 215 220
Leu Trp Asn Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
225 230 235
<210> 153
<211> 246
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 153
Ser Thr Val Met Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Ser Val Ser Asn Asp
20 25 30
Val Ala Trp Tyr Gln Gln Lys Pro Cys Gln Ser Pro Lys Val Leu Ile
35 40 45
Tyr Phe Ala Ser Asn Arg Tyr Thr Gly Val Pro Asp Arg Phe Ser Gly
50 55 60
Ser Gly Tyr Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala
65 70 75 80
Glu Asp Val Ala Val Tyr Phe Cys Gln Gln Asp Tyr Ser Ser Pro Leu
85 90 95
Thr Phe Gly Ala Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser
100 105 110
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ile Gln Leu Val Gln
115 120 125
Ser Gly Ser Glu Leu Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys
130 135 140
Lys Ala Ser Gly Tyr Thr Phe Thr Asn Phe Phe Val Asn Trp Val Lys
145 150 155 160
Gln Ala Pro Gly Lys Gly Leu Lys Trp Met Gly Trp Ile Asn Thr Tyr
165 170 175
Thr Gly Glu Pro Ser Tyr Ala Asp Asp Phe Lys Gly Arg Phe Ala Phe
180 185 190
Ser Leu Asp Ala Ser Ala Ser Thr Ala Tyr Leu Gln Ile Ser Ser Leu
195 200 205
Lys Ala Glu Asp Met Ala Thr Tyr Phe Cys Thr Arg Arg Thr Asn Tyr
210 215 220
Tyr Gly Thr Ser Tyr Tyr Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr
225 230 235 240
Thr Val Thr Val Ser Ser
245
<210> 154
<211> 458
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 154
Arg Ile Val Met Thr Gln Ser Pro Gly Thr Leu Ser Val Ser Pro Gly
1 5 10 15
Glu Thr Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Phe Ser Asn Met
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Ser Gly Gln Pro Pro Arg Leu Leu Ile
35 40 45
Tyr Gly Val Ser Thr Arg Ala Ala Gly Val Pro Ala Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Asn Leu Gln Ser
65 70 75 80
Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Asp Trp Pro Arg
85 90 95
Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Arg Lys Arg Thr Val Ala
100 105 110
Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser
115 120 125
Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu
130 135 140
Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser
145 150 155 160
Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu
165 170 175
Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val
180 185 190
Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys
195 200 205
Ser Phe Asn Arg Gly Glu Cys Gly Gly Gly Gly Ser Gly Gly Gly Gly
210 215 220
Ser Gly Gly Gly Gly Ser Glu Val Gln Leu Val Gln Ser Gly Gly Gly
225 230 235 240
Val Val Arg Pro Gly Gly Ser Leu Arg Leu Pro Cys Ala Ala Ser Gly
245 250 255
Phe Thr Phe Asp Asp Tyr Gly Met Ser Trp Val Arg Gln Ala Pro Gly
260 265 270
Lys Gly Leu Glu Trp Val Ser Gly Ile Asn Trp Asn Gly Gly Ser Thr
275 280 285
Gly Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn
290 295 300
Ala Lys Asn Ser Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp
305 310 315 320
Thr Ala Leu Tyr His Cys Ala Arg Gly Gly Asp Asp Ala Phe Asp Ile
325 330 335
Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly
340 345 350
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
355 360 365
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
370 375 380
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
385 390 395 400
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
405 410 415
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
420 425 430
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys
435 440 445
Ser Cys Asp Lys Thr Ser Gly Gln Ala Gly
450 455
<210> 155
<211> 239
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 155
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro
85 90 95
Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Gln Leu Val
115 120 125
Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser
130 135 140
Cys Val Ala Ser Gly Phe Thr Phe Ser Asn Ser Trp Met Ser Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Asn Ile Asn Glu
165 170 175
Asp Gly Ser Glu Lys Phe Tyr Val Asp Ser Val Lys Gly Arg Phe Thr
180 185 190
Phe Ser Arg Asp Asn Ala Glu Asn Ser Leu Tyr Leu Gln Met Asn Ser
195 200 205
Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Val His Trp
210 215 220
Tyr Phe His Leu Trp Gly Arg Gly Thr Leu Val Thr Val Ser Ser
225 230 235
<210> 156
<211> 242
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 156
Asn Ile Val Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Val Gly Thr Ala
20 25 30
Val Ala Trp Tyr Gln Gln Lys Pro Asp Gln Ser Pro Lys Leu Leu Ile
35 40 45
Tyr Trp Thr Ser Thr Arg His Thr Gly Val Pro Asp Arg Phe Thr Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Ile Ala Thr Tyr Phe Cys His Gln Tyr Asn Ser Tyr Asn Thr
85 90 95
Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Gly Ser
100 105 110
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Thr Leu Lys Glu
115 120 125
Ser Gly Pro Val Leu Val Lys Pro Thr Glu Thr Leu Thr Leu Thr Cys
130 135 140
Thr Phe Ser Gly Phe Ser Leu Ser Thr Ser Gly Met Gly Val Gly Trp
145 150 155 160
Ile Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala His Ile Trp
165 170 175
Trp Asp Asp Asp Val Tyr Tyr Asn Pro Ser Leu Lys Ser Arg Leu Thr
180 185 190
Ile Thr Lys Asp Ala Ser Lys Asp Gln Val Ser Leu Lys Leu Ser Ser
195 200 205
Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Val Arg Arg Arg Ala
210 215 220
Thr Gly Thr Gly Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val
225 230 235 240
Ser Ser
<210> 157
<211> 679
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 157
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Val Asn Thr Ala
20 25 30
Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Ser Ala Ser Phe Leu Tyr Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Arg Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln His Tyr Thr Thr Pro Pro
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala
100 105 110
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly
115 120 125
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala
130 135 140
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
180 185 190
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser
195 200 205
Phe Asn Arg Gly Glu Cys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
210 215 220
Gly Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu
225 230 235 240
Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe
245 250 255
Asn Ile Lys Asp Thr Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys
260 265 270
Gly Leu Glu Trp Val Ala Arg Ile Tyr Pro Thr Asn Gly Tyr Thr Arg
275 280 285
Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Ala Asp Thr Ser
290 295 300
Lys Asn Thr Ala Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr
305 310 315 320
Ala Val Tyr Tyr Cys Ser Arg Trp Gly Gly Asp Gly Phe Tyr Ala Met
325 330 335
Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr
340 345 350
Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser
355 360 365
Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu
370 375 380
Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His
385 390 395 400
Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser
405 410 415
Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys
420 425 430
Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu
435 440 445
Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro
450 455 460
Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
465 470 475 480
Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val
485 490 495
Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp
500 505 510
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr
515 520 525
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp
530 535 540
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu
545 550 555 560
Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg
565 570 575
Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys
580 585 590
Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp
595 600 605
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys
610 615 620
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser
625 630 635 640
Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser
645 650 655
Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser
660 665 670
Leu Ser Leu Ser Pro Gly Lys
675
<210> 158
<211> 246
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 158
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Ala Ala Val Gly Thr Tyr
20 25 30
Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Ser Ala Ser Tyr Arg Lys Arg Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys His Gln Tyr Tyr Thr Tyr Pro Leu
85 90 95
Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg Thr Gly Gly
100 105 110
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln
115 120 125
Leu Val Gln Ser Gly Ser Glu Leu Lys Lys Pro Gly Ala Ser Val Lys
130 135 140
Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Glu Phe Gly Met Asn
145 150 155 160
Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Trp Ile
165 170 175
Asn Thr Lys Thr Gly Glu Ala Thr Tyr Val Glu Glu Phe Lys Gly Arg
180 185 190
Phe Val Phe Ser Leu Asp Thr Ser Val Ser Thr Ala Tyr Leu Gln Ile
195 200 205
Ser Ser Leu Lys Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Trp
210 215 220
Asp Phe Tyr Asp Tyr Val Glu Ala Met Asp Tyr Trp Gly Gln Gly Thr
225 230 235 240
Thr Val Thr Val Ser Ser
245
<210> 159
<211> 392
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 159
Ser Arg Ala Ala Thr Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu
1 5 10 15
Leu Leu Trp Val Pro Gly Ser Thr Gly Asp Ile Gln Leu Thr Gln Ser
20 25 30
Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys
35 40 45
Ser Ala Ser Ser Ser Val Arg Phe Ile His Trp Tyr Gln Gln Lys Pro
50 55 60
Gly Lys Ala Pro Lys Arg Leu Ile Tyr Asp Thr Ser Lys Leu Ala Ser
65 70 75 80
Gly Val Pro Ser Arg Pro Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr
85 90 95
Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys
100 105 110
Gln Gln Trp Ser Ser Ser Pro Phe Thr Phe Gly Gln Gly Thr Lys Val
115 120 125
Glu Ile Lys Gly Ser Thr Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly
130 135 140
Gly Gly Gly Ser Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu
145 150 155 160
Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe
165 170 175
Asn Ile Lys Asp Tyr Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys
180 185 190
Gly Leu Glu Trp Val Ala Trp Ile Asp Pro Glu Asn Gly Asp Thr Glu
195 200 205
Phe Val Pro Lys Phe Gln Gly Arg Ala Thr Ile Ser Ala Asp Thr Ser
210 215 220
Lys Asn Thr Ala Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr
225 230 235 240
Ala Val Tyr Tyr Cys Lys Thr Gly Gly Phe Trp Gly Gln Gly Thr Leu
245 250 255
Val Thr Val Ser Ser Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
260 265 270
Pro Pro Cys Gly Gly Gly Ser Ser Gly Gly Gly Ser Gly Gly Gln Pro
275 280 285
Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr
290 295 300
Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser
305 310 315 320
Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr
325 330 335
Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr
340 345 350
Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe
355 360 365
Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys
370 375 380
Ser Leu Ser Leu Ser Pro Gly Lys
385 390
<210> 160
<211> 243
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 160
Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly
1 5 10 15
Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser
20 25 30
Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
35 40 45
Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val
50 55 60
Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
65 70 75 80
Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln
85 90 95
Tyr Tyr Ser Tyr Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile
100 105 110
Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
115 120 125
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
130 135 140
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp His
145 150 155 160
Ala Ile His Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Met
165 170 175
Gly Tyr Phe Ser Pro Gly Asn Asp Asp Phe Lys Tyr Ser Gln Lys Phe
180 185 190
Gln Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Ala Ser Thr Ala Tyr
195 200 205
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
210 215 220
Ala Arg Ser Leu Asn Met Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr
225 230 235 240
Val Ser Ser
<210> 161
<211> 243
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 161
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Arg Ser Trp
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Glu Lys Ala Pro Lys Ser Leu Ile
35 40 45
Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Asn Ser Tyr Pro Leu
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Gly Gly Gly Gly Ser
100 105 110
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val Gln
115 120 125
Ser Gly Ala Glu Val Lys Lys Pro Gly Ser Ser Val Lys Val Ser Cys
130 135 140
Lys Ala Phe Gly Gly Thr Phe Ser Ser Tyr Ala Ile Ser Trp Val Arg
145 150 155 160
Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Arg Ile Ile Arg Phe
165 170 175
Leu Gly Lys Thr Asn His Ala Gln Lys Phe Gln Gly Arg Val Thr Leu
180 185 190
Thr Ala Asp Lys Ser Thr Asn Thr Ala Tyr Met Glu Leu Ser Ser Leu
195 200 205
Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly Glu Pro Gly Asp
210 215 220
Arg Asp Pro Asp Ala Val Asp Ile Trp Gly Gln Gly Thr Met Val Thr
225 230 235 240
Val Ser Ser
<210> 162
<211> 249
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 162
Asp Ile Val Met Thr Gln Thr Pro Leu Ser Ser Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asp Gly Asn Thr Tyr Leu Ser Trp Leu His Gln Arg Pro Gly Gln Pro
35 40 45
Pro Arg Leu Leu Ile Tyr Lys Ile Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ala Gly Thr Ala Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Ala
85 90 95
Thr Gln Leu Pro Arg Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105 110
Arg Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
115 120 125
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg
130 135 140
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr
145 150 155 160
Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
165 170 175
Ala Val Ile Trp Tyr Asp Gly Ser Asn Lys Tyr Tyr Val Asp Ser Val
180 185 190
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
195 200 205
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
210 215 220
Ala Arg Asp Gly Trp Gln Gln Leu Ala Pro Phe Asp Tyr Trp Gly Gln
225 230 235 240
Gly Thr Leu Val Thr Val Ser Ser Ala
245
<210> 163
<211> 237
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 163
Asp Ile Lys Met Thr Gln Ser Pro Ser Ser Met Tyr Ala Ser Leu Gly
1 5 10 15
Glu Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Ile Asn Asn Tyr
20 25 30
Leu Ser Trp Phe Gln Gln Lys Pro Gly Lys Ser Pro Lys Thr Leu Ile
35 40 45
Tyr Arg Ala Asn Arg Leu Val Asp Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Gln Asp Tyr Ser Leu Thr Ile Ser Ser Leu Glu Tyr
65 70 75 80
Glu Asp Met Gly Ile Tyr Tyr Cys Leu Lys Tyr Asp Glu Phe Pro Tyr
85 90 95
Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser
100 105 110
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Val Lys Leu Val Glu
115 120 125
Ser Gly Gly Gly Leu Val Lys Pro Gly Gly Ser Leu Lys Leu Ser Cys
130 135 140
Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr Thr Met Ser Trp Val Arg
145 150 155 160
Gln Thr Pro Glu Lys Arg Leu Glu Trp Val Ala Thr Ile Ser Ser Gly
165 170 175
Gly Thr Tyr Thr Tyr Tyr Pro Asp Ser Val Lys Gly Arg Phe Thr Ile
180 185 190
Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr Leu Gln Met Ser Ser Leu
195 200 205
Lys Ser Glu Asp Thr Ala Met Tyr Tyr Cys Thr Arg Glu Ala Ile Phe
210 215 220
Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala
225 230 235
<210> 164
<211> 239
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 164
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Arg Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Ile Gly Ala Ser Thr Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Gly Gln Val Ile Pro
85 90 95
Pro Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Gly Gly Gly Gly Ser
100 105 110
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Gln Leu Leu Glu
115 120 125
Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys
130 135 140
Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr Ala Met Ser Trp Val Arg
145 150 155 160
Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ala Ile Ser Gly Ser
165 170 175
Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile
180 185 190
Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu
195 200 205
Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Lys Gly Trp Leu Gly
210 215 220
Asn Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
225 230 235
<210> 165
<211> 441
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 165
Glu Ile Val Met Thr Gln Thr Pro Ala Thr Leu Ser Val Ser Ala Gly
1 5 10 15
Glu Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Ser Val Ser Asn His
20 25 30
Val Thr Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile
35 40 45
Tyr Ser Ala Ser Asn Arg Tyr Ser Gly Val Pro Ala Arg Phe Ser Gly
50 55 60
Ser Gly Tyr Gly Thr Glu Phe Thr Phe Thr Ile Ser Ser Val Gln Ser
65 70 75 80
Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Asp Tyr Ser Ser Phe Gly
85 90 95
Gln Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val
100 105 110
Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser
115 120 125
Val Val Cys Tyr Glu Leu Leu Ala Glu Asn Asn Phe Tyr Pro Arg Glu
130 135 140
Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser
145 150 155 160
Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu
165 170 175
Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val
180 185 190
Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys
195 200 205
Ser Phe Asn Arg Gly Glu Cys Gly Gly Gly Gly Ser Gly Gly Gly Gly
210 215 220
Ser Gly Gly Gly Gly Ser Lys Ile Val Met Thr Gln Thr Pro Ala Thr
225 230 235 240
Leu Ser Val Ser Ala Gly Glu Arg Val Thr Ile Thr Cys Lys Ala Ser
245 250 255
Gln Ser Val Ser Asn His Val Thr Trp Tyr Gln Gln Lys Pro Gly Gln
260 265 270
Ala Pro Arg Leu Leu Ile Tyr Ser Ala Ser Asn Arg Tyr Ser Gly Val
275 280 285
Pro Ala Arg Phe Ser Gly Ser Gly Tyr Gly Thr Glu Phe Thr Phe Thr
290 295 300
Ile Ser Ser Val Gln Ser Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln
305 310 315 320
Asp Tyr Ser Ser Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg Thr
325 330 335
Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu
340 345 350
Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro
355 360 365
Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly
370 375 380
Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr
385 390 395 400
Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His
405 410 415
Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val
420 425 430
Thr Lys Ser Phe Asn Arg Gly Glu Cys
435 440
<210> 166
<211> 685
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 166
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Gly Asn Phe
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Tyr Thr Ser Arg Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Lys Thr Leu Pro Tyr
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Asp Ile Arg Thr Val
100 105 110
Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys
115 120 125
Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg
130 135 140
Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn
145 150 155 160
Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser
165 170 175
Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys
180 185 190
Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr
195 200 205
Lys Ser Phe Asn Arg Gly Glu Cys Gly Gly Gly Gly Ser Gly Gly Gly
210 215 220
Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val Glu Ser Gly Gly
225 230 235 240
Gly Val Val Gln Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser
245 250 255
Gly Phe Thr Phe Ser Asn Phe Gly Met His Trp Val Arg Gln Ala Pro
260 265 270
Gly Lys Gly Leu Glu Trp Val Ala Tyr Ile Ser Ser Gly Gly Ser Ser
275 280 285
Ile Asn Tyr Ala Asp Thr Val Lys Gly Arg Phe Thr Ile Ser Arg Asp
290 295 300
Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu
305 310 315 320
Asp Thr Ala Val Tyr Tyr Cys Thr Arg Gly Gly Thr Gly Thr Arg Ser
325 330 335
Leu Tyr Tyr Phe Asp Tyr Trp Gly Gln Gly Thr Thr Val Thr Val Ser
340 345 350
Ser Asp Ile Pro Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
355 360 365
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
370 375 380
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
385 390 395 400
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
405 410 415
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
420 425 430
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys
435 440 445
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
450 455 460
Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu
465 470 475 480
Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu
485 490 495
Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys
500 505 510
Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys
515 520 525
Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu
530 535 540
Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys
545 550 555 560
Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys
565 570 575
Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser
580 585 590
Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys
595 600 605
Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln
610 615 620
Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly
625 630 635 640
Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln
645 650 655
Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn
660 665 670
His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
675 680 685
<210> 167
<211> 239
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 167
Glu Ile Val Met Thr Gln Thr Pro Leu Ile Leu Ser Val Thr Ile Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser
20 25 30
Asn Gly Lys Thr Tyr Leu Asn Trp Leu Leu Gln Arg Pro Gly Gln Ser
35 40 45
Pro Lys Arg Leu Ile Tyr Leu Val Ser Lys Leu Asp Ser Gly Val Pro
50 55 60
Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Tyr Cys Val Gln Gly
85 90 95
Ser His Phe Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Ala Asp Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
115 120 125
Gly Gly Ser Gly Pro Glu Leu Lys Lys Pro Gly Glu Thr Val Lys Ile
130 135 140
Tyr Cys Lys Ala Ser Gly Tyr Ser Phe Arg Asp Tyr Ser Val His Trp
145 150 155 160
Val Lys Gln Ala Pro Gly Lys Gly Leu Lys Trp Met Gly Trp Ile Asn
165 170 175
Thr Glu Thr Gly Glu Pro Thr Tyr Val Asp Glu Phe Lys Gly Arg Phe
180 185 190
Ala Phe Phe Leu Glu Ala Ser Ala Asn Thr Val Tyr Leu Gln Ile Ser
195 200 205
Asn Leu Lys Asn Glu Asp Thr Ala Thr Tyr Phe Cys Asp Tyr Arg Phe
210 215 220
Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala Ala Lys
225 230 235
<210> 168
<211> 243
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 168
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Ser Ser Trp
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Glu Lys Ala Pro Lys Ser Leu Ile
35 40 45
Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Glu Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Glu Ala Thr Tyr Tyr Cys Gln Gln Tyr Asn Gly Tyr Pro Tyr
85 90 95
Thr Glu Gly Gln Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser
100 105 110
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Gln Leu Val Glu
115 120 125
Ser Gly Gly Gly Leu Val Lys Pro Gly Gly Ser Leu Arg Leu Ser Cys
130 135 140
Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr Ser Met Asn Trp Val Arg
145 150 155 160
Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Thr Ser Ser
165 170 175
Ser Ser Tyr Ile Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile
180 185 190
Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln Met Asn Ser Leu
195 200 205
Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Arg Arg Tyr
210 215 220
Phe Asp Trp Phe Pro Ile Asp Tyr Arg Gly Gln Gly Thr Leu Val Thr
225 230 235 240
Val Ser Ser
<210> 169
<211> 285
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 169
Met Arg Val Pro Ala Gln Leu Leu Gly Leu Leu Leu Leu Cys Phe Pro
1 5 10 15
Gly Ala Arg Cys Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser
20 25 30
Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly
35 40 45
Ile Thr Asn Tyr Leu Ala Trp Phe Gln Gln Lys Pro Gly Lys Ala Pro
50 55 60
Lys Ser Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser
65 70 75 80
Lys Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Ser Leu Thr Ile Ser
85 90 95
Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Asn
100 105 110
Ser Tyr Pro Ile Thr Phe Gly Gln Gly Thr Arg Leu Glu Ile Lys Gly
115 120 125
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Met Glu
130 135 140
Leu Gly Leu Arg Trp Val Leu Leu Val Ala Leu Leu Arg Gly Val Gln
145 150 155 160
Cys Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly
165 170 175
Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asn
180 185 190
Tyr Val Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
195 200 205
Val Ala Ile Ile Trp Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala Asp Ser
210 215 220
Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu
225 230 235 240
Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr
245 250 255
Cys Ala Gly Gly Tyr Asn Trp Asn Tyr Glu Tyr His Tyr Tyr Gly Met
260 265 270
Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser
275 280 285
<210> 170
<211> 279
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 170
Met Asp Phe Gln Val Gln Ile Phe Ser Phe Leu Leu Ile Ser Ala Ser
1 5 10 15
Val Ile Leu Ser Ser Gly Gln Ile Gly Leu Thr Gln Ser Pro Ala Ile
20 25 30
Met Ser Ala Ser Pro Gly Glu Lys Val Thr Met Thr Cys Ser Ala Ser
35 40 45
Ser Ser Ile Ser Tyr Met His Trp Tyr Gln Gln Lys Pro Gly Thr Ser
50 55 60
Pro Lys Thr Trp Ile Tyr Asp Thr Ser Lys Leu Ala Ser Gly Val Pro
65 70 75 80
Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile
85 90 95
Ser Ser Met Glu Ala Glu Asp Ala Ala Thr Tyr Tyr Cys His Gln Arg
100 105 110
Ser Ser His His Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Gly
115 120 125
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Met Gly
130 135 140
Trp Leu Trp Asn Leu Leu Phe Leu Met Ala Ala Ala Gln Ser Ala Gln
145 150 155 160
Ala Gln Ile Gln Leu Val Gln Ser Gly Pro Glu Leu Lys Lys Pro Gly
165 170 175
Glu Thr Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Thr
180 185 190
Tyr Gly Met Ser Trp Val Lys Gln Ala Pro Gly Arg Gly Leu Lys Trp
195 200 205
Met Gly Trp Ile Asn Pro Tyr Ser Gly Val Pro Thr Tyr Ala Val Asp
210 215 220
Phe Lys Gly Arg Phe Ala Phe Ser Leu Glu Thr Ser Ala Ser Thr Ala
225 230 235 240
Tyr Leu Gln Ile Asn Asn Leu Lys Asn Glu Asp Thr Ala Thr Tyr Phe
245 250 255
Cys Ala Arg Gly Gly Arg Arg Gly Asp Phe Gly Tyr Trp Gly Gln Gly
260 265 270
Thr Thr Leu Thr Val Ser Ser
275
<210> 171
<211> 244
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 171
Asp Ile Val Met Thr Gln Ser Pro Ser Ser Leu Thr Val Thr Ala Gly
1 5 10 15
Glu Lys Val Thr Met Ile Cys Lys Ser Ser Gln Ser Leu Leu Asn Ser
20 25 30
Gly Asp Gln Lys Asn Tyr Leu Thr Trp Tyr Gln Gln Lys Pro Gly Gln
35 40 45
Pro Pro Lys Leu Leu Ile Phe Trp Ala Ser Thr Arg Glu Ser Gly Val
50 55 60
Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
65 70 75 80
Ile Ser Ser Val Gln Ala Glu Asp Leu Ala Val Tyr Tyr Cys Gln Asn
85 90 95
Asp Tyr Ser Tyr Pro Leu Thr Phe Gly Ala Gly Thr Lys Leu Glu Leu
100 105 110
Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
115 120 125
Gln Val Gln Leu Gln Gln Ser Asp Ala Glu Leu Val Lys Pro Gly Ser
130 135 140
Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp His
145 150 155 160
Ala Ile His Trp Val Lys Gln Lys Pro Glu Gln Gly Leu Glu Trp Ile
165 170 175
Gly His Phe Ser Pro Gly Asn Thr Asp Ile Lys Tyr Asn Asp Lys Phe
180 185 190
Lys Gly Lys Ala Thr Leu Thr Val Asp Arg Ser Ser Ser Thr Ala Tyr
195 200 205
Met Gln Leu Asn Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Phe Cys
210 215 220
Lys Thr Ser Thr Phe Phe Phe Asp Tyr Trp Gly Gln Gly Thr Thr Leu
225 230 235 240
Thr Val Ser Ser
<210> 172
<211> 254
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 172
Gln Val Gln Leu Glu Gln Ser Gly Leu Gly Leu Val Lys Pro Ser Gln
1 5 10 15
Thr Leu Ser Leu Thr Cys Ala Ile Ser Gly Asp Thr Val Ser Ser Asp
20 25 30
Ser Ala Ala Trp Asn Trp Ile Arg Gln Ser Pro Ser Arg Gly Leu Glu
35 40 45
Trp Leu Gly Arg Thr Tyr Tyr Arg Ser Lys Trp Phe Asn Asp Tyr Ala
50 55 60
Val Ser Val Lys Gly Arg Ile Thr Ile Asn Ser Asp Thr Ser Lys Asn
65 70 75 80
Gln Phe Ser Leu Gln Leu Asn Ser Val Thr Pro Glu Asp Thr Ala Val
85 90 95
Tyr Tyr Cys Ala Arg Ser Asn Ser Tyr Tyr Tyr Tyr Ala Met Asp Val
100 105 110
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser
115 120 125
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Leu Thr Gln
130 135 140
Pro Ser Ser Leu Ser Ala Ser Pro Gly Ala Ser Ala Ser Leu Thr Cys
145 150 155 160
Thr Leu Arg Ser Gly Ile Asn Val Gly Ile Tyr Arg Ile Tyr Trp Tyr
165 170 175
Gln Gln Arg Pro Gly Ser Pro Pro Gln Ile Leu Leu Thr Tyr Lys Ser
180 185 190
Asp Ser Asp Lys Tyr Gln Gly Ser Gly Val Pro Ser Arg Phe Ser Gly
195 200 205
Ser Lys Asp Ala Ser Ala Asn Ala Gly Ile Leu Leu Ile Ser Gly Leu
210 215 220
Gln Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Met Ile Trp His Ser Gly
225 230 235 240
Gly Trp Val Phe Gly Gly Gly Thr Lys Val Thr Val Leu Gly
245 250
<210> 173
<211> 264
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 173
Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu
1 5 10 15
His Ala Ala Arg Pro Gln Ser Val Leu Thr Gln Pro Ala Ser Val Ser
20 25 30
Gly Ser Pro Gly Gln Ser Val Thr Ile Ser Cys Thr Gly Thr Ser Ser
35 40 45
Asp Val Gly Gly Tyr Asn Tyr Val Ser Trp Tyr Gln Gln His Pro Gly
50 55 60
Lys Pro Pro Lys Leu Met Ile Tyr Glu Val Ser Lys Arg Pro Ser Gly
65 70 75 80
Val Pro Asp Arg Phe Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu
85 90 95
Thr Ile Ser Gly Leu Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser
100 105 110
Ser His Thr Ser Ser Asn Thr Leu Ile Phe Gly Gly Gly Thr Lys Val
115 120 125
Thr Val Leu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly
130 135 140
Gly Ser Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro
145 150 155 160
Gly Glu Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Thr Phe Thr
165 170 175
Asn Tyr Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu
180 185 190
Trp Met Gly Arg Ile Tyr Pro Ser Asp Ser Tyr Thr Asn Tyr Ser Pro
195 200 205
Ser Phe Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr
210 215 220
Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr
225 230 235 240
Tyr Cys Ala Arg Asp Leu Glu Pro Thr His His Tyr Ser Trp Gly Gln
245 250 255
Gly Thr Leu Val Thr Val Ser Ser
260
<210> 174
<211> 267
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 174
Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu
1 5 10 15
His Ala Ala Arg Pro Leu Pro Val Leu Thr Gln Pro Pro Ser Ala Ser
20 25 30
Gly Thr Pro Gly Gln Arg Val Thr Ile Ser Cys Ser Gly Ser Ser Ser
35 40 45
Asn Ile Gly Ser Asn Ala Val Asp Trp Tyr Gln Gln Leu Pro Gly Thr
50 55 60
Ala Pro Lys Leu Leu Ile Tyr Thr Asn Asn Arg Arg Pro Ser Gly Val
65 70 75 80
Pro Asp Arg Phe Ser Gly Ser Lys Ser Gly Thr Ser Gly Ser Leu Ala
85 90 95
Ile Ser Gly Leu Gln Phe Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Ala
100 105 110
Trp Asp Asp Ser Leu Ser Gly Val Ile Phe Gly Gly Gly Thr Lys Val
115 120 125
Thr Val Leu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly
130 135 140
Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro
145 150 155 160
Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Glu Asp Thr Phe Ser
165 170 175
Ser Tyr Val Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu
180 185 190
Trp Met Gly Ala Phe Ile Pro Leu Leu Gly Arg Val His Tyr Ala Gln
195 200 205
Glu Phe Gln Gly Arg Leu Thr Ile Thr Ala Asp Glu Ser Thr Gly Thr
210 215 220
Ala Tyr Met Glu Leu Lys Gly Leu Arg Ser Asp Asp Thr Ala Met Tyr
225 230 235 240
Tyr Cys Ala Arg Asp Gln Gly Phe Ala Gly Asp Asp Ala Phe Asp Ile
245 250 255
Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser
260 265
<210> 175
<211> 266
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 175
Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu
1 5 10 15
His Ala Ala Arg Pro Gln Pro Val Leu Thr Gln Asp Pro Val Val Ser
20 25 30
Val Ala Leu Gly Gln Thr Val Arg Ile Thr Cys Gln Gly Asp Ser Leu
35 40 45
Arg Ser Tyr Tyr Ala Thr Trp Tyr Gln Gln Lys Pro Gly Leu Ala Pro
50 55 60
Val Arg Val Ile Phe Gly Lys Asn Ser Arg Pro Ser Gly Ile Pro Asp
65 70 75 80
Arg Phe Ser Gly Ser Ser Ser Gly Asn Thr Ala Ser Leu Thr Ile Thr
85 90 95
Gly Ala Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Asn Ser Trp Asp
100 105 110
Asn Ser Ala Asn His Pro Val Phe Gly Gly Gly Thr Lys Leu Thr Val
115 120 125
Leu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Arg Lys Pro Gly Ser
145 150 155 160
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Asp Asn Phe Asn Asn Tyr
165 170 175
Gly Ile Thr Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
180 185 190
Gly Arg Leu Ile Thr Val Leu Gly Leu Asp Asn Tyr Ala Gln Lys Phe
195 200 205
Gln Gly Arg Leu Thr Ile Thr Ala Asp Glu Ser Thr Gly Thr Ala Tyr
210 215 220
Met Glu Leu Thr Gly Leu Glu Pro Glu Asp Thr Ala Val Tyr Tyr Cys
225 230 235 240
Ala Arg Asp Ile Met Ser Pro Glu Ala Ile Asp Ala Phe Asp Val Trp
245 250 255
Gly Gln Gly Thr Leu Val Thr Val Ser Ser
260 265
<210> 176
<211> 265
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 176
Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu
1 5 10 15
His Ala Ala Arg Pro Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu
20 25 30
Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln
35 40 45
Asp Val Ser Asn Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala
50 55 60
Pro Lys Leu Leu Ile Tyr Gly Ala Ser Asn Arg Gln Thr Gly Val Pro
65 70 75 80
Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile
85 90 95
Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Glu
100 105 110
Asp Arg Phe Pro Thr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
115 120 125
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu
130 135 140
Val Gln Leu Val Gln Ser Gly Ala Glu Val Arg Lys Pro Gly Ser Ser
145 150 155 160
Val Lys Val Ser Cys Lys Ala Ser Gly Asp Asn Phe Asn Asn Tyr Gly
165 170 175
Ile Thr Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly
180 185 190
Arg Leu Ile Thr Val Leu Gly Leu Asp Asn Tyr Ala Gln Lys Phe Gln
195 200 205
Gly Arg Leu Thr Ile Thr Ala Asp Glu Ser Thr Gly Thr Ala Tyr Met
210 215 220
Glu Leu Thr Gly Leu Glu Pro Glu Asp Thr Ala Val Tyr Tyr Cys Ala
225 230 235 240
Arg Asp Ile Met Ser Pro Glu Ala Ile Asp Ala Phe Asp Val Trp Gly
245 250 255
Gln Gly Thr Leu Val Thr Val Ser Ser
260 265
<210> 177
<211> 270
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 177
Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu
1 5 10 15
His Ala Ala Arg Pro Glu Ile Val Leu Thr Gln Ser Ala Ser Ser Leu
20 25 30
Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Thr Ser Gln
35 40 45
Asn Ile Tyr Arg Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala
50 55 60
Pro Lys Leu Leu Ile Phe Gly Ala Ser Thr Leu Gln Thr Gly Val Pro
65 70 75 80
Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile
85 90 95
Thr Gly Leu Gln Pro Glu Asp Leu Ala Thr Tyr Tyr Cys Gln His Ser
100 105 110
Phe Lys Leu Pro Phe Thr Phe Gly Gln Gly Thr Arg Leu Glu Ile Lys
115 120 125
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln
130 135 140
Met Leu Val Gln Ser Gly Ala Glu Val Lys Arg Pro Gly Ser Ser Val
145 150 155 160
Thr Val Ser Cys Glu Thr Ser Gly Asp Thr Phe Ser Arg Tyr Ala Ile
165 170 175
Ser Trp Leu Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Leu Gly Trp
180 185 190
Ile Ser Gly Asn Ser Gly Arg Ala Asp Tyr Ala Gln Asn Phe Gln Gly
195 200 205
Arg Val Thr Met Thr Thr Asp Arg Ser Thr Ser Thr Ala Tyr Leu Asn
210 215 220
Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg
225 230 235 240
Asp Ala Pro Met Leu Phe Gly Val Arg Gly Gly Gly Tyr Tyr Phe Gly
245 250 255
Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser
260 265 270
<210> 178
<211> 258
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 178
Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu
1 5 10 15
His Ala Ala Arg Pro Gln Pro Val Leu Thr Gln Asp Pro Ala Val Ser
20 25 30
Val Ala Leu Gly Gln Thr Val Arg Ile Thr Cys Gln Gly Asp Ser Leu
35 40 45
Arg Lys Tyr Tyr Ala Ser Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro
50 55 60
Arg Leu Val Met Tyr Asp Glu Asn Asp Arg Pro Ser Gly Ile Pro Asp
65 70 75 80
Arg Phe Ser Gly Ser Ser Ser Gly Asn Thr Ala Ser Leu Thr Ile Thr
85 90 95
Gly Ala Gln Ala Asp Asp Glu Ala Asp Tyr Tyr Cys Asn Ser Arg Asp
100 105 110
Ser Ser Gly His His Val Val Phe Gly Gly Gly Thr Lys Val Thr Val
115 120 125
Leu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Gln Met Gln Leu Val Gln Ser Gly Ala Glu Val Arg Arg Pro Gly Ser
145 150 155 160
Ser Val Lys Val Ser Cys Lys Thr Ser Gly Gly Thr Leu Asn Asn Tyr
165 170 175
Asp Ile Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
180 185 190
Gly Trp Met Asn Pro Thr Ser Gly Gln Ala Asp Phe Ala Gln Lys Phe
195 200 205
Gln Gly Arg Val Ser Met Thr Arg Asp Thr Ser Ile Asn Thr Ala Phe
210 215 220
Met Glu Leu Asn Thr Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
225 230 235 240
Val Arg Arg Gly Gly Lys Tyr Trp Gly Gln Gly Thr Leu Val Thr Val
245 250 255
Ser Ser
<210> 179
<211> 267
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 179
Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu
1 5 10 15
His Ala Ala Arg Pro Ser Tyr Glu Leu Thr Gln Pro Pro Ser Val Ser
20 25 30
Val Ala Pro Gly Gln Thr Ala Arg Ile Thr Cys Gly Gly Asp Ala Leu
35 40 45
Pro Asn Asn Ser Val Arg Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro
50 55 60
Val Leu Val Ile Tyr Gly Asn Ser Glu Arg Pro Ser Gly Ile Pro Glu
65 70 75 80
Arg Phe Ser Gly Ser Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser
85 90 95
Gly Thr Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Gln Val Ser Asp
100 105 110
Lys Ser Thr Lys Tyr Ser Val Phe Gly Gly Gly Thr Lys Leu Thr Val
115 120 125
Leu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
130 135 140
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
145 150 155 160
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asn Tyr
165 170 175
Trp Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
180 185 190
Ala Gly Ile Ser Ala Ser Gly Gly Asn Lys Tyr Tyr Ala Asp Ser Val
195 200 205
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
210 215 220
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
225 230 235 240
Ala Lys Gly Pro Ile Gln Leu Lys Arg His Lys Tyr Val Leu Asp Tyr
245 250 255
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
260 265
<210> 180
<211> 108
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 180
Gln Pro Val Leu Thr Gln Asp Pro Val Val Ser Val Ala Leu Gly Gln
1 5 10 15
Thr Val Arg Ile Thr Cys Gln Gly Asp Ser Leu Arg Ser Tyr Tyr Ala
20 25 30
Thr Trp Tyr Gln Gln Lys Pro Gly Leu Ala Pro Val Arg Val Ile Phe
35 40 45
Gly Lys Asn Ser Arg Pro Ser Gly Ile Pro Asp Arg Phe Ser Gly Ser
50 55 60
Ser Ser Gly Asn Thr Ala Ser Leu Thr Ile Thr Gly Ala Gln Ala Glu
65 70 75 80
Asp Glu Ala Asp Tyr Tyr Cys Asn Ser Trp Asp Asn Ser Ala Asn His
85 90 95
Pro Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
100 105
<210> 181
<211> 122
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 181
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Arg Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Asp Asn Phe Asn Asn Tyr
20 25 30
Gly Ile Thr Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Arg Leu Ile Thr Val Leu Gly Leu Asp Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Leu Thr Ile Thr Ala Asp Glu Ser Thr Gly Thr Ala Tyr
65 70 75 80
Met Glu Leu Thr Gly Leu Glu Pro Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Ile Met Ser Pro Glu Ala Ile Asp Ala Phe Asp Val Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 182
<211> 127
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 182
Gln Met Leu Val Gln Ser Gly Ala Glu Val Lys Arg Pro Gly Ser Ser
1 5 10 15
Val Thr Val Ser Cys Glu Thr Ser Gly Asp Thr Phe Ser Arg Tyr Ala
20 25 30
Ile Ser Trp Leu Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Leu Gly
35 40 45
Trp Ile Ser Gly Asn Ser Gly Arg Ala Asp Tyr Ala Gln Asn Phe Gln
50 55 60
Gly Arg Val Thr Met Thr Thr Asp Arg Ser Thr Ser Thr Ala Tyr Leu
65 70 75 80
Asn Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala
85 90 95
Arg Asp Ala Pro Met Leu Phe Gly Val Arg Gly Gly Gly Tyr Tyr Phe
100 105 110
Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser
115 120 125
<210> 183
<211> 107
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 183
Glu Ile Val Leu Thr Gln Ser Ala Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Thr Ser Gln Asn Ile Tyr Arg Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Phe Gly Ala Ser Thr Leu Gln Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Thr Gly Leu Gln Pro
65 70 75 80
Glu Asp Leu Ala Thr Tyr Tyr Cys Gln His Ser Phe Lys Leu Pro Phe
85 90 95
Thr Phe Gly Gln Gly Thr Arg Leu Glu Ile Lys
100 105
<210> 184
<211> 114
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 184
Gln Met Gln Leu Val Gln Ser Gly Ala Glu Val Arg Arg Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Thr Ser Gly Gly Thr Leu Asn Asn Tyr
20 25 30
Asp Ile Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Trp Met Asn Pro Thr Ser Gly Gln Ala Asp Phe Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Ser Met Thr Arg Asp Thr Ser Ile Asn Thr Ala Phe
65 70 75 80
Met Glu Leu Asn Thr Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Arg Gly Gly Lys Tyr Trp Gly Gln Gly Thr Leu Val Thr Val
100 105 110
Ser Ser
<210> 185
<211> 108
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 185
Gln Pro Val Leu Thr Gln Asp Pro Ala Val Ser Val Ala Leu Gly Gln
1 5 10 15
Thr Val Arg Ile Thr Cys Gln Gly Asp Ser Leu Arg Lys Tyr Tyr Ala
20 25 30
Ser Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Val Met Tyr
35 40 45
Asp Glu Asn Asp Arg Pro Ser Gly Ile Pro Asp Arg Phe Ser Gly Ser
50 55 60
Ser Ser Gly Asn Thr Ala Ser Leu Thr Ile Thr Gly Ala Gln Ala Asp
65 70 75 80
Asp Glu Ala Asp Tyr Tyr Cys Asn Ser Arg Asp Ser Ser Gly His His
85 90 95
Val Val Phe Gly Gly Gly Thr Lys Val Thr Val Leu
100 105
<210> 186
<211> 123
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 186
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asn Tyr
20 25 30
Trp Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ala Gly Ile Ser Ala Ser Gly Gly Asn Lys Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Lys Gly Pro Ile Gln Leu Lys Arg His Lys Tyr Val Leu Asp Tyr
100 105 110
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 187
<211> 108
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 187
Ser Tyr Glu Leu Thr Gln Pro Pro Ser Val Ser Val Ala Pro Gly Gln
1 5 10 15
Thr Ala Arg Ile Thr Cys Gly Gly Asp Ala Leu Pro Asn Asn Ser Val
20 25 30
Arg Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile Tyr
35 40 45
Gly Asn Ser Glu Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser
50 55 60
Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Gly Thr Gln Ala Glu
65 70 75 80
Asp Glu Ala Asp Tyr Tyr Cys Gln Val Ser Asp Lys Ser Thr Lys Tyr
85 90 95
Ser Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
100 105
<210> 188
<211> 20
<212> PRT
<213> 人工序列（Artificial Sequence）
<400> 188
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
1 5 10 15
Gly Gly Gly Ser
20
<210> 189
<211> 19
<212> DNA
<213> 人工序列（Artificial Sequence）
<400> 189
tgcatttgaa ctccttgcc 19
<210> 190
<211> 20
<212> DNA
<213> 人工序列（Artificial Sequence）
<400> 190
ccatcaatct tccacttgac 20

Claims (10)

1.一种结合ACPP的抗体，其中所述抗体包含重链可变区HVR和轻链可变区LVR，所述重链可变区为SEQ ID NO: 83的氨基酸序列，所述轻链可变区为SEQ ID NO: 82的氨基酸序列。
2.如权利要求1所述的抗体，其中所述HVR被连接到人IgG链恒定区，并且所述人IgG是IgG1或IgG3。
3.如权利要求1所述的抗体，其中所述抗体被缀合到细胞毒性剂，并且所述细胞毒性剂是放射性同位素或毒素。
4.如权利要求1所述的抗体，其中所述抗体是scFv，并且所述LVR通过接头连接到HVR。
5.一种嵌合抗原受体CAR，所述CAR包含抗原结合结构域，所述抗原结合结构域包含权利要求1-4中任一项所述的抗体。
6.一种多核苷酸，所述多核苷酸编码权利要求1-4中任一项所述的抗体或编码权利要求5所述的嵌合抗原受体CAR。
7.一种修饰的细胞，所述修饰的细胞包含权利要求6所述的多核苷酸。
8.如权利要求7所述的修饰的细胞，其中所述修饰的细胞是T细胞。
9.如权利要求5所述的嵌合抗原受体CAR，其中所述CAR包含细胞外结构域、跨膜结构域和细胞内结构域，所述细胞外结构域包含结合抗原的结合结构域。
10.如权利要求9所述的嵌合抗原受体CAR，其中所述细胞内结构域包含共刺激信号传导区，所述共刺激信号传导区包括选自以下各项的共刺激分子的细胞内结构域：CD27、CD28、4-1BB、OX40、CD30、CD40、PD-1、ICOS、淋巴细胞功能相关抗原-1、CD2、CD7、LIGHT、NKG2C、B7-H3及其任何组合。
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