CN111979269B - 表达免疫系统-刺激分子的溶瘤性单纯疱疹病毒载体 - Google Patents
表达免疫系统-刺激分子的溶瘤性单纯疱疹病毒载体 Download PDFInfo
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Abstract
本发明提供了一种表达免疫系统‑刺激分子的溶瘤性单纯疱疹病毒载体，其包含IL12、IL15和IL15受体α亚单位的表达盒，表达盒的侧翼具有经修饰的ICP47启动子。本发明的单纯疱疹病毒载体经过结构改造，可以更好地复制与表达外源基因，表达的蛋白具有良好的稳定性，适于实际应用。
Description
技术领域
本发明总体上涉及表达刺激免疫系统的分子的溶瘤性单纯疱疹病毒(oHSV)载体。
背景技术
溶瘤病毒(OV)已经成为通过溶瘤效应特异性破坏癌细胞的一种治疗方案，其杀伤机制的特征在于，通过病毒裂解行复制的过程使癌细胞裂解。
本发明克服了目前的商业化溶瘤病毒的缺点，并且毒性低、表达水平高、稳定性好。
发明内容
简而言之，本文披露内容涉及保护针对IL12、IL15和/或IL受体15α亚单位中的一种或多种的单纯疱疹病毒载体(HSV载体)。在一种实施方式中，单纯疱疹病毒HSV载体包含IL12、IL15和IL15受体α亚单位的表达盒，表达盒的侧翼具有经修饰的ICP47启动子。
在一种实施方式中，所述经修饰的ICP47启动子的序列至少包含SEQ ID No.584。
在一种实施方式中，所述经修饰的ICP47启动子的序列为SEQ ID No.584。
在一种实施方式中，IL12、IL15和IL15受体α亚单位的编码序列之间的框内具有编码自剪切肽2A的核酸序列。
在一种实施方式中，所述自剪切肽2A的氨基酸序列为：
VKQTLNFDLLKLAGDVESNPGP、QCTNYALLKLAGDVESNPGP、ATNF-SLLKQAGDVEENPGP、HYAGYFADLLIHDIETNPGP、GIFNAHYAGYFADLLIHDIETNPGP、KAVRGYHADYYKQRLIHDVEMNPGP、GATNFSLLKLAGDVELNPGP、EGRGSLLTCGDVEENPGP、AARQMLLLLSGDVETNPGP、FLRKRTQLLMSGDVESNPGP、GSWTDILLLLSGDVETNPGP、TRAEUEDELIRAGIESNPGP、AKFQIDKILISGDVELNPGP、SKFQIDKILISGDIELNPGP、SSIIRTKMLVSGDVEENPGP或CDAQRQKLLLSGDIEQNPGP。
在一种实施方式中，一个或多个IRES序列位于IL12、IL15和IL15受体α亚单位的编码序列之间。
在一种实施方式中，IL15和IL15受体α亚单位通过双向启动子表达。
在一种实施方式中，IL15和IL15受体α亚单位各自跟随一个编码Lys5或Glu5的核酸序列。
在一种实施方式中，hIL15受体α亚单位选自由变体1(SEQ ID NO:3)、变体2(SEQID NO:4)、变体3(SEQ ID NO:5)、变体4(SEQ ID NO:6)组成的组。
在一种实施方式中，包含IL12、IL15和IL15受体α亚单位的表达盒被插入到HSV的内部重复区或HSV基因组的末端重复区中。
在一种实施方式中，单纯疱疹病毒HSV载体进一步包含一种或多种PD-L1阻断肽的表达盒。
在一种实施方式中，PD-L1阻断肽的表达盒被插入HSV病毒基因的UL3和UL4之间。
在一种实施方式中，单纯疱疹病毒HSV载体进一步包含编码连接至所述PD-L1阻断肽的3’-端的Fc区的序列。
在一种实施方式中，连接至所述PD-L1阻断肽的3’-端的Fc区的序列为编码IgG4Fc区域的序列。
在一种实施方式中，在单纯疱疹病毒HSV载体的ICP4或ICP27调控区中进一步包含NFkB和OCT4/SOX2增强元件。
在一种实施方式中，单纯疱疹病毒HSV载体的ICP34.5基因部分缺失，或无功能。
本文披露的内容还涉及一种制剂，该制剂由下列组分组成：
利用根据权利要求1至15任一项所述的单纯疱疹病毒HSV载体所表达的病毒的悬液，甘油，水；
其中，制剂中甘油的浓度为5±3％。
本文披露的内容还涉及一种药物组合物，所述药物组合物包含本发明的单纯疱疹病毒HSV载体，和可药用载体。
本文披露的内容还涉及本文所述的单纯疱疹病毒HSV载体，或本文所述的制剂，或本文所述的药物组合物在制备治疗癌症的药物中的应用。
在一种实施方式中，所述癌症选自肝癌，胃癌，肠癌，肺癌，乳腺癌，鼻咽癌，头颈部肿瘤，膀胱癌、结肠癌、直肠癌、肾癌、小细胞肺癌、非小细胞肺癌、食道癌、胆囊癌、卵巢癌、胰腺癌、子宫颈癌、甲状腺癌、前列腺癌、皮肤癌、急性淋巴细胞性白血病、慢性骨髓性白血病、急性成淋巴细胞性白血病、B细胞淋巴瘤、T细胞淋巴瘤、霍奇金淋巴瘤、非霍奇金淋巴瘤、毛细胞淋巴瘤、伯基特氏淋巴瘤、急性或慢性骨髓性白血病、黑色素瘤、子宫内膜癌、头颈癌、成胶质细胞瘤、骨肉瘤白血病、淋巴瘤、骨髓瘤和肉瘤。
在一种实施方式中，所述的治疗癌症通过皮下注射、瘤内注射或静脉注射的方式来给药
发明内容部分已经简要地介绍了某些构思，在具体实施方式部分中将对其进行进一步详细描述。除非另外记载，否则发明内容部分既不是意在确定本文要求保护主题的关键或必要特征，也不是意在限制本文保护主题的范围。
发明的效果
本发明克服了目前的商业化溶瘤病毒的缺点，并且毒性低、表达水平高、稳定性好。
本发明通过对病毒结构的改造，例如对病毒某些基因启动子区域的改造，使得经过改造的病毒在感染细胞后能够在更长时间存在于被感染的细胞中躲避免疫细胞攻击，从而可以更好地复制与表达外源基因。
本发明还对载体所携带的外源基因进行了改进，例如构建外源多肽与适当的末端结构形成的融合蛋白，使表达的蛋白具有良好的稳定性，适于实际应用。
本发明还提供了保存病毒的优化的介质，在利用本发明的载体表达出病毒后，优化的介质可在较长时间内保持病毒活性，便于载体及病毒的工业应用。
下文中将详细描述一种或多种实施方式。与一种示例性实施方式结合示出或者描述的特征可以与其他实施方式的特征组合。因此，能够将本文所述的各种实施方式中的任一种进行组合以提供进一步的实施方式。当有必要采用本文中所确定的各专利、申请或公开的构思时，能够改变这些实施方式的方面以提供更进一步的实施方式。根据说明书、附图和权利要求书将能够了解其他的特征、目的和优势。
附图说明
根据附图和各种实施方式的以下详细描述将能够了解本文披露内容的示例性特征、其性质和各种优势。参照附图描述了非限制性和非穷尽性的实施方式，其中，除非另外指出，在各视图中类似的标记和标号代表类似的部分。附图中元件的大小和相对位置不一定是按比例绘制。例如，为了改善附图的可读性而选择、放大、放置各元件的形状。为了在附图中易于识别，已经选择了如所绘制的元件的特定形状。下文中参照附图描述了一种或多种实施方式，其中：
图1A和图1B是示例性oHSV载体的示意图。
图2示出了病毒hVG001-1-2的经修饰的ICP34.5区(SEQ ID NO:572)的示意图。
图3示出了病毒hVG001-1-2的经修饰的UL54启动子区(SEQ ID NO:573)的示意图。
图4示出了具有PD-L1阻断子插入的hVG001-1-2病毒基因组(SEQ ID NO:574)的示意图。
图5示出了hVG001-1-2修饰的TR区(SEQ ID NO:575)的示意图。
图6A-图6C示出了在细胞感染hVG001-1-2之后IL-12表达的ELISA和蛋白质印迹分析表达。
图7A-图7C示出了在细胞感染hVG001-1-2之后IL-15表达的ELISA和蛋白质印迹分析表达。
图8A-图8C示出了在细胞感染hVG001-1-2之后IgG4表达的ELISA和蛋白质印迹分析表达。
图9A-图9C为：(A)示例性构建体的示意图，其中bi-CMV启动子驱动IL-15Rα和IL-15的Sushi结构域的表达，以及(B-C)DNA序列和示意图(SEQ ID No:557)。
图10A-图10C为：(A)示例性构建体的示意图，其中bi-CMV启动子驱动IL-15和IL-15Rα变体4的表达，以及(B-C)DNA序列和示意图(SEQ ID No:558)。
图11A-图11C为：(A)示例性构建体的示意图，其中bi-CMV启动子驱动IL-15-K5和IL-15RαSushi结构域-E5的表达，以及(B-C)DNA序列和示意图(SEQ ID No:559)。
图12A-图12D为：(A)示例性构建体的示意图，其中bi-CMV启动子驱动IL-15-K5和IL-15Rα变体4-E5的表达，以及(B-D)DNA序列和示意图(SEQ ID No:560)。
图13A-图13D为：(A)示例性构建体的示意图，其中EF1α启动子控制IL-15-IRES-IL-15RαSushi结构域的表达，以及(B-D)DNA序列和示意图(SEQ ID No:561)。
图14A-图14D为：(A)示例性构建体的示意图，其中EF1α启动子控制IL-15-IRES-IL-15Rα变体4的表达，以及(B-D)DNA序列和示意图(SEQ ID No:562)。
图15A-图15D为：(A)示例性构建体的示意图，其中EF1α启动子控制IL-15K5-IRES-IL-15RαSushi结构域E5的表达，以及(B-D)DNA序列和示意图(SEQ ID No:563)。
图16A-图16D为：(A)示例性构建体的示意图，其中EF1α启动子控制IL-15K5-IRES-IL-15Rα变体4E5的表达，以及(B-D)DNA序列和示意图(SEQ ID No:564)。
图17A-图17E为：(A)示例性构建体的示意图，其中CMV启动子控制IL-12-p2A-IL-15-p2A-IL-15RαSushi结构域的表达，以及(B-E)DNA序列和示意图(SEQ ID No:565)。
图18A-图18E为：(A)示例性构建体的示意图，其中CMV启动子控制IL-12-p2A-IL-15-p2A-IL-15Rα变体1的表达，以及(B-E)DNA序列和示意图(SEQ ID No:566)。
图19A-图19D为：(A)示例性构建体的示意图，其中CMV启动子控制IL-12-p2A-IL-15K5-p2A-IL-15RαSushi结构域E5的表达，以及(B-D)DNA序列和示意图(SEQ ID No:567)。
图20A、图20B、图20C、图20D、图20D续为：(A)示例性构建体的示意图，其中CMV启动子控制IL-12-p2A-IL-15K5-p2A-IL-15Rα变体1-E5的表达，以及(B)、(C)、(D)、(D)续为DNA序列和示意图(SEQ ID No:568)。
图21A、图21B、图21C示出了通过阻断肽结合至PD-1的PD-L1的百分比抑制的图表。
图22A-图22B示出了PD-L1抑制肽通过抗-CD3刺激的人外周血单核细胞对靶细胞的细胞毒性的影响。
图23A和图23B示出了仅IL-12、仅IL15加IL-15Rα、以及IL-12和IL15/1L-15Rα共同对在人外周血单核细胞中产生IFNγ和TNFα的影响。
图24A和图24B示出了IL-12和IL15/IL-15Rα通过外周血单核细胞对U87和MDA-MB-23肿瘤细胞的细胞毒性的影响。
图25A-图25C示出了用携带PD-L1阻断肽或者人IL15/15Ra的病毒(VG001-PLBh和VG001-15h)感染肿瘤细胞后IL12,IL15和PD-L1阻断肽的表达。图25D、图25E示出了用携带PD-L1阻断肽或者人IL15/15Ra的病毒(VG001-PLBh和VG001-15h)感染肿瘤细胞后的结果。
图26A-图26D示出了各种构建体的体外测定的结果。图26A-图26B示出了用表达IL-12、IL-15和PD-L1阻断子的IL-TF-Fc质粒进行细胞转染的结果。图26C-图26D示出了包括hVG001-1-2在内的多种突变体病毒进行细胞转染的结果。
图27A-图27E示出了在人肿瘤细胞系和Vero细胞系上进行的针对hVG001-1-2和HSV-345的细胞活力测定的结果。
图28A-图28J示出了各种构建体的体外测定的结果。图28A-图28E示出了mVG001-1-2和HSV-345在小鼠肿瘤细胞系和Vero细胞系上的细胞活力测定的结果；图28F-图28H示出了在CT26小鼠肿瘤细胞的mVG001-1-2感染之后转基因表达的表征,图28I-图28J示出了用mVG001-1-2感染CT26细胞后刺激外周单核细胞释放细胞毒性因子的表征。
图29A-图29C示出了在各种细胞系的hVG001-1-2或VG001-1.7感染之后转基因表达的体外表征的结果。图29D-图29E显示了被感染的肿瘤细胞刺激外周单核细胞释放细胞因子和细胞杀伤活性。
图30A-图30G示出了评估hVG001-1-2在体外杀死各种人类癌细胞的能力的测定结果。
图31A-图31G示出了mVG001-1-2和hVG001-1-2构建体在体的抑制肿瘤生长的结果。
图32A-图32C示出了不同病毒在三种不同人细胞系上的生长曲线。
图33A-图33D示出了mVG001-1-2和HSV-345在小鼠肿瘤细胞系和Vero细胞系上的生长曲线。
图34A-图34E示出了hVG001-1-2和HSV-345在人肿瘤细胞系和Vero细胞系上的生长曲线。
图35A-图35D示出了病毒改性的影响。
图36A-图36D体外表达的外源基因的有效性。
图37A和图37B提供了小鼠模型中注射病毒后病毒携带的外源基因在瘤内的表达。
图38A-图38C提供了VG001-1-2在免疫应答方面的影响。
图39是经修饰的示例性oHSV病毒载体(VG001-1-2)的示意图。
图40示出病毒VG001-1-2的经修饰的ICP34.5区域(SEQ ID NO:599)。
图41示出病毒VG001-1-2的经修饰的UL54启动子区域(SEQ ID NO:596)。
图42示出VG001-1-2中插入了PD-L1阻断子的区域(SEQ ID NO:589)。
图43示出VG001-1-2中经修饰的末端重复(terminal repeats,TR)区域(SEQ IDNO:576)，该区域携带编码IL-12、IL-15和IL-15受体α亚单位的表达盒，并具有US2(ICP47)侧翼。
图44为短(S)型启动子A(SEQ ID NO:583)的示意图。
图45为中(M)型启动子A(SEQ ID NO:584)的示意图。
图46为长(L)型启动子A(SEQ ID NO:585)的示意图。
图47为启动子B(survivin)(SEQ ID NO:586)的示意图。
图48A-图48F为VG001-1-2中携带的IL12-IL15-IL15RA1表达盒及其侧翼的序列(SEQ ID NO:576)。
图49A-图49C为VG001-1-2中经修饰的UL54(ICP27)启动子-调控区的序列(SEQ IDNO.596)。
图50A-图50D为VG001-1-2中在UL3和UL4之间的基因区域中插入PD-L1阻断子的序列(SEQ ID No.589)。
图51为VG001-1-2中包含的经修饰的ICP34.5区的序列(SEQ ID NO.599)。
图52为短(S)型启动子A的序列(SEQ ID NO:583)。
图53为中(M)型启动子A的序列(SEQ ID NO:584)。
图54为长(S)型启动子A的序列(SEQ ID NO:585)。
图55为启动子B(survivin)的序列(SEQ ID NO:586)。
图56A-图56B示出VG001-1-2病毒对(A)人类癌细胞、(B)小鼠癌细胞造成细胞毒性的测定结果。
图57A-图57C示出细胞感染VG001-1-2病毒后(A)表达IL-12、(B)表达IL-15、(C)表达PD-L1阻断子。
图58示出对细胞感染VG001-1-2后产生的PD-L1阻断子进行ELISA分析的结果。
图59示出对细胞感染VG001-1-2后产生的PD-L1阻断子进行基于细胞的分析的结果。
图60A-图60D示出IL-12、IL-15/IL-15RA和PD-L1阻断子在体外协同地促进免疫细胞功能。
图61A-图61D示出VG001-1-2病毒肿瘤内接种的效果。
图62A-图62B示出用mVG001-1-2病毒处理肿瘤细胞产生的基因表达和T细胞活性的效果。
图63A-图63D示出mVG001-1-2处理对肿瘤内淋巴细胞群的影响。
图64A-图64B示出最小剂量人IL12或人IL15/IL15RA对免疫细胞功能的影响。
图65A、图65B示出VG001-1-2病毒的生物分布。
图66示出对接受VG001-1-2处理的荷瘤小鼠进行免疫相关基因表达水平定量检测的结果。
图67示出感染不同病毒后的细胞的流式分析结果。
图68示出以不同配方的介质保存的病毒的滴度分析结果。
图69示出病毒表达的不同结构的融合蛋白的稳定性测试结果。
图70示出VG001-1-2载体的结构。
具体实施方式
通过本文中包括的本发明优选实施方式和实施例的如下详细描述可以更容易地理解本文披露内容。
披露概述
通过参照本文中所包括的本发明优选实施方式和实施例的以下详细描述可以更容易地理解本发明。简言之，本文披露内容提供了溶瘤性单纯疱疹病毒1型或2型载体，其表达免疫刺激分子。代表性的载体包含编码一种或多种IL-12、IL-15和IL-15Rα的表达盒。某些载体编码鼠或人IL-12、人IL-15、人IL-15Rα。在某些实施方式中，该载体编码鼠或人IL-12、hIL15和hIL15受体α亚单位。在其他的实施方式中，该载体编码hIL-12、HIL15和HIL15受体α亚单位。这三种蛋白可以在一个、两个或三个转录本上表达。当在同一个转录本上表达时，继而发生的转录后过程导致单个蛋白的表达。在这样的情况下，编码区被编码自剪切肽2A或者IRES序列隔开。该编码区也可以通过双向启动子表达。该HSV载体可选地表达其能够分泌的一种或多种PD-L1阻断肽。
A.oHSV载体
溶瘤病毒是一种优选地以选择性方式裂解癌细胞的病毒(oncolysis)。在分化细胞中选择性复制超过非分化细胞的病毒经常是溶瘤性的。适合用于本文的溶瘤病毒包括单纯疱疹病毒1和2，也可以包括非人的疱疹病毒，例如BHV或者其他。
单纯疱疹病毒(HSV)1和2是感染人的疱疹病毒科的成员。HSV基因组含有两个独特区，其被称为长独特(UL)区和短独特(US)区。这些区域中每一个的侧翼具有一对反向末端重复序列。存在75种已知的开放阅读框。该病毒基因组已被工程化改造以开发用于例如，癌症治疗中的溶瘤病毒。可以通过HSV ICP34.5(也被称作γ34.5)基因的突变实现HSV的肿瘤选择性复制。HSV含有ICP34.5的两个拷贝，已知使ICP34.5基因的一个或两个拷贝失活的突变体缺少神经毒力，即，非致病的/非神经毒性的并且是溶瘤性的。
适合的溶瘤性HSV可以来源于HSV-1或HSV-2，包括任何实验室毒株或临床分离物。在一些实施方式中，oHSV可以是或者可以来源于实验室毒株HSV-1株17、HSV-1株F、或HSV-2株HG52之一。在其他实施方式中，其可以是任何临床分离毒株或其他非实验室毒株JS-1。其他适合的HSV-1病毒包括HrrR3(Goldsten和Weller,J.Virol.62,196-205,1988)；G2O7(Mineta等人，Nature Medicine.1(9):938-943,1995；Kooby等人，The FASEB Journal,13(11):1325-1334,1999)；G47Delta(Todo等人Proceedings of the National Academy ofSciences.2001；98(11):6396-6401)；HSV 1716(Mace等人Head&Neck,2008；30(8):1045-1051；Harrow等人，GeneTherapy.2004；11(22):1648-1658)；HF10(Nakao等人，CancerGeneTherapy.2011；18(3):167-175)；NV1020(Fong等人，Molecular Therapy,2009；17(2):389-394)；T-VEC(Andtbacka等人，Journal of Clinical Oncology,2015:33(25):2780-8)；J100(Gaston等人，PloS one,2013；8(11):e81768)；M002(Parker等人，Proceedings ofthe National Academy of Sciences,2000；97(5):2208-2213)；NV1042(Passer等人，Cancer Gene Therapy.2013；20(1):17-24)；G2O7-IL2(Carew等人，Molecular Therapy,2001；4(3):250-256)；rQNestin34.5(Kambara等人，Cancer Research,2005；65(7):2832-2839)；G47Δ-mIL-18(Fukuhara等人，Cancer Research,2005；65(23):10663-10668)；以及在题为“HSV Vectors with Enhanced Replication in Cancer Cells(在癌细胞中增强复制的HSV载体)”的PCT/US2017/030308和题为“Compositions and Methods of UsingStat1/3Inhibitors with Oncolytic Herpes Virus(利用Stat1/3抑制子和溶瘤性疱疹病毒的组合物和方法)”的PCT/US2017/018539等PCT申请中披露的那些载体，上述全部内容以引用方式结合与本文作为参考。
oHSV载体可以具有至少一个γ34.5基因的修饰、突变、或缺失。该载体缺少完整的γ34.5基因。在一些实施方式中，两个基因均缺失、发生突变或经修饰。在其他实施方式中，一个基因缺失而另一个基因发生突变或经修饰。能够缺失任一个内源(native)γ34.5基因。在一种实施方式中，包含γ34.5基因和ICP4基因的末端重复区域缺失。突变(例如核苷酸改变、插入和缺失)使得该基因不可表达或者产物失活。可以用miRNA靶序列在其3’UTR中对γ34.5基因进行修饰。该靶序列结合在肿瘤细胞中的表达低于在其正常对照物中表达的miRNA。在一些实施方式中，体外构建该经修饰的或突变的γ34.5基因并将其插入到oHSV载体中作为病毒基因的替代物。当该经修饰的或突变的γ34.5基因仅替代一个γ34.5基因时，另一个γ34.5基因缺失。γ34.5基因可以包含另外的变化，例如具有外源启动子。
oHSV可以具有另外的突变，其可以包括失能突变(例如，缺失、取代、插入)，其会影响病毒的毒力或其复制的能力。例如，可以在ICP6、ICPO、ICP4、ICP27、ICP47、ICP 24、ICP56中的任意一种或多种中进行突变。优选地，这些基因(可选地在其中适合的该基因的两个拷贝中)之一中的突变会导致HSV不能表达相应的功能性多肽(或该能力下降)。在一些实施方式中，用在靶细胞中选择性激活的，或者在诱导子递送后可诱导的或在细胞事件后或特定环境中可诱导的启动子来替代病毒基因的启动子。在特定的实施方式中，肿瘤特异性启动子驱动HSV复制至关重要的病毒基因的表达。在某些实施方式中，ICP4或ICP27或二者的表达受到外源启动子的控制，例如，肿瘤特异性启动子。示例性的肿瘤特异性启动子包括生存素(survivin)或端粒酶(telomerase)；其他适合的肿瘤特异性启动子可以特异于单一肿瘤类型并且是本领域已知的。可以存在其他元件。在一些情况下，存在增强子(例如NF-kB/OCT4/SOX2增强子)，例如在ICP4或ICP27或二者的调控区中。而且，5’UTR可以是外源性的，例如来自生长因子基因(例如FGF)的5’UTR。
oHSV还可以具有非HSV来源的基因和核苷酸序列。例如，oHSV基因组中可以具有编码前药的序列、编码细胞因子或其他免疫刺激因子的序列、肿瘤特异性启动子、可诱导的启动子、增强子、与宿主T细胞同源的序列、以及其他序列。示例性的序列编码IL12、IL15、OX40L、PD-L1阻断子或PD-1阻断子。对于编码产物的序列，其操作性地连接至表达所需或者所期望的启动子序列和其他调控序列(例如，增强子、多腺苷酸化信号序列)。
病毒基因的调控区可以被修饰以包含影响表达的应答元件。示例性的应答元件包括NF-κB、Oct-3/4-SOX2、增强子、沉默子、cAMP应答元件、CAAT增强子结合序列和隔离子的应答元件。也可以包括其他应答元件。可以用不同启动子来替换该病毒启动子。该启动子的选择取决于因素的数量，例如想要使用的HSV载体、患者的治疗、基本状态或病况、以及应用诱导子的难易程度(针对可诱导的启动子)。对于癌症治疗，通常当启动子被替换时，其会具有细胞特异性或组织特异性或肿瘤特异性启动子。肿瘤特异性、细胞特异性和组织特异性启动子是本领域已知的。其他基因元件也可以被修饰。例如，可以用外源UTR替换病毒基因的5’UTR。
B.免疫刺激分子
oHSV载体包含编码一种或多种免疫刺激分子(例如，IL-12、IL-15和IL-15Rα)的核酸序列。序列表中列出了示例性IL-12、IL-15和IL-15Rα的氨基酸序列(SEQ ID NOs:1-6)。编码该氨基酸序列的任意DNA序列是适合的，但通常会针对指定接受oHSV的受试者群体中的优选表达来选择密码子。
1.IL-12
白介素12(IL-12)主要由树枝状细胞、巨噬细胞和单核细胞相应于细菌(例如，脂多糖类)、病原体或活化的T细胞产生。IL-12能够诱导IFNγ产生、细胞增殖，并激活自然杀伤细胞和T细胞。其对于T细胞分化为Th1细胞也是关键的。IL-12还能够抑制肿瘤生长。鼠IL-12对于鼠和人细胞的活性相等，并且均适合于在oHSV载体中使用。
生物学活性IL-12是一种异源二聚体分子，其由通过二硫桥共价连接的35kDa(p35)和40kDa(p40)亚单位构成。两个亚单位的同时表达对于产生异源二聚体是必要的。在oHSV载体中，IL-12表达可以多种方式实现。能够在单独的构建体中表达两个亚单位，每一个具有一个启动子，或者在一个构建体中从双向启动子开始表达，或者从一个在编码区中具有例如IRES或自切割肽的元件的构建体开始表达。可替代地，该亚单位能够作为单链表达。例如，能够通过将p40和p35的编码区与接头连接来产生能性单链IL-12融合蛋白，该接头通常由Ser或Gly构成或者由Ser和Gly的组合构成，例如Ser5、(Gly4Ser)3或Gly6Ser(例如，Lieschke等人，Nature Biotechnology 15:35,1997；Lode等人，PNAS 95:2475,1998；替代性融合构建体还参见WO 2015/095249)。通常以使得该结构与具有最大的灵活度的方式选择接头的序列和长度(Chen等人，Adv Drug Deliv Rev.65:1357,2013)。能够利用计算机程序来选择接头序列。一种这样的程序被称作LINKER(Crasto和Feng，Protein EngDesign&Selection 13:309)。一种示例性的单链IL-12具有SEQ ID NO:1的氨基酸序列。可以进行氨基酸取代、插入和缺失，只要该IL-12保持功能即可。
2.IL-15
IL-15是一种调控自然杀伤细胞以及T细胞激活和增殖的细胞因子，并且能够具有其他的生物学活性。存在信号肽序列不同并且具有完全相同的成熟蛋白序列的两种同种型,。具有较长信号肽的同种型的序列(有时被称作LSP-IL15)的GenBank(NCBI)登陆号为NP000576，而具有较短信号肽的同种型的序列(有时被称作SSP-IL15)的登陆号为NP 751915。任一同种型都适合于在oHSV载体中使用。可以存在氨基酸插入、缺失和取代，例如在多态性中发现的，只要该蛋白结合IL-15即可。
在一些实施方式中，IL-15和IL-15Rα均具有选择性二聚体化的卷曲螺旋的C-末端肽。文献中教导了大量适合的肽(参见，例如，Tripet等人，Protein Engineering 9:1029,1996；Aronsson等人,Sci Rep 5:14063,2015)。通常，卷曲螺旋的氨基酸序列具有hpphppp形式的疏水性(h)和极性(p)残基的七肽重复。两种示例性的卷曲螺旋为K螺旋(KVSALKE,SEQ ID No.7)和E螺旋(EVSALEK,SEQ ID NO.8)。通常，使用3-6个串联拷贝。在本文中的一些实施方式中，均使用5个串联拷贝。K5(KVSALKEKVSALKEKVSALKEKVSALKEKVSALKE,SEQ IDNO.9)和E5(EVSALEKEVSALEKEVSALEKEVSALEKEVSALEK,SEQ ID NO.10)。K螺旋和E螺旋被设计为带有相反电荷，因此IL-15与一种卷曲螺旋融合，而IL-15Rα则融合至带相反电荷的卷曲螺旋。SEQ ID NO:12中示出了融合于E5的示例性Sushi结构域，SEQ ID NO:13中示出了融合于E5的示例性IL-15Rα变体4，SEQ ID NO:14中示出了融合于E5的示例性IL-15Rα变体1，以及SEQ ID NO:15中示出了融合于K5的示例性IL-15。
3.IL-15Rα亚单位
白介素-15受体α亚单位(IL-15Rα)是结合IL-15的复合物的三个亚单位之一。该α亚单位以高亲和性结合IL-15并且能够独立于其他亚单位独立地结合于IL-15。存在至少四种变体(同种型)，本文中称作变体1(NP 002180.1)(SEQ ID NO:3)；变体2(NP 751950.2)(SEQ ID NO:4)；变体3(NP 001230468.1)(SEQ ID NO:5)；和变体4(NP_001243694)(SEQ IDNO:6)。α亚单位含有Sushi结构域(aka补体调节蛋白(complement control protein，CCP)、短同源重复序列(short consensus repeats，SCRs)或SUSHI重复)，其是保留IL-15结合活性的最短区域。典型的Sushi结构域为约60-70个氨基酸，其含有含有形成两个二硫键的四个半胱氨酸并且在蛋白质-蛋白质相互作用中是共有基序。IL-15Rα的Sushi结构域包含残基31至约95(对应于变体1)(SEQ ID NO:11)。Sushi结构域在其他变体中的位置是已知的。sIL-15Rα中半胱氨酸的氨基酸取代消除了其抑制急性炎症的能力并且T细胞在体内响应于同种异型抗原(Wei等人，J Immunol.167:277,2001)。
oHSV载体包含编码IL-15Rα、IL-15Rα的变体或Sushi结构域的核酸序列。通常，该蛋白由先导肽表达，而在一些实施方式中，该先导肽来自IL-15Rα。其他的先导肽是本领域已知的。可以存在氨基酸取代，只要该蛋白结合IL-15即可。自然替代、多态性是已知的。
4.PD-L1阻断肽
程序性死亡配体1(PD-L1)在抑制免疫系统方面起作用，可能是由于结合PD-1受体的作用。阻断蛋白质-蛋白质相互作用已经显示出能够改善癌症治疗。
oHSV载体可以表达PD-L1阻断肽。适合的肽包括TAHPSPSPRSAGQF(SEQ ID NO:16)、EYRMSPSNQT(SEQ ID NO:17)、YYRMSPSNQT(SEQ ID NO:18)、TRYPSPSPKPEGRF(SEQ ID NO:19)和WNRLSPSNQT(SEQ ID NO:20)。其他适合的肽包括表4中列出的那些(SEQ ID NOs:21-500)。通常，阻断肽由先导序列表达。先导序列是本领域公知的。其包括免疫球蛋白κ链先导序列(METDTLLLWVLLLWVPGSTG；SEQ ID NO:501)和IL-2先导序列(MYRMQLLSCIALSLALVTNS；SEQ ID NO:502)。当存在多于一个阻断肽时，该肽通常会被赋予柔性的连接肽分离。该接头通常为Gly或Ser或者富含Gly/Ser。在(SEQ ID NOs:503-519)中示出了适合接头的实例(还参见，Chichili等人，Protein Science 22:153,2013)。可以有一个肽拷贝或者两个拷贝或者三个拷贝或者更多拷贝。多个拷贝通常是随机的并且可以在拷贝之间具有接头。该阻断肽构建体还可以在肽的C-末端包含Fc序列，或者具有或不具有铰链区的免疫球蛋白Fc序列。尽管任何Fc区都是用，但是通常，Fc会是来自IgG亚类之一，例如，人IgG1、人IgG2、人IgG3，以及人IgG4或其鼠对应物。
C.元件的组织
分子IL-12、IL-15和IL-15Rα在oHSV载体中能够具有各种个不同构造。例如，每一个分子可以各自地从单独的启动子/调控区表达或者从一个或两个单独的启动子/调控区共表达。
在某些实施方式中，该分子中的两种或三种在单个转录本中从一个启动子表达并且它们的编码序列被IRES(内部核糖体进入位点)序列。IRES区吸引真核核糖体翻译起始复合体并因此使得翻译起始能够在mRNA的中部进行并且独立于常用的5’-端帽结构。适合的IRES序列是公知的并且许多适合的IRES序列能够在经实验确认的IRES序列的IRESite’s表达碱基中找到(参见，例如，http://iresite.org/IRESite_web.php？page＝browse_plasmids；2016年5月26日收稿)。
在各种实施方式中，这三种基因以任意顺序存在并且被一个或多个IRES序列隔开。该IRES序列可以相同或者不同。在基因/IRES连接点或IRES/IRES连接点出可以存在另外的序列。
在某些实施方式中，该分子中的两种或三种在单个转录本中从一个启动子表达，并且它们的编码序列被一个或多个自剪切肽2A隔开。这些肽为短肽(约18-22个氨基酸)并且在编码序列之间插入到框内。在翻译期间，核糖体跳过了在2A肽C-端的甘氨酰-脯氨酰肽键的合成，导致2A肽和其相邻最接近下游蛋白之间的切割。因此，它们从相同mRNA产生等摩尔水平的多种基因产物。该"切割"在C-端处的gly-pro残基之间发生，这意味着上游顺反子将会具有加入到其其C-末端的另外残基，而下游顺反子则从脯氨酸开始。SEQ ID NOs:520-535中示出了示例性的p2A肽序列。
影响分子的共表达的其他方式是使用双向启动子。双向启动子是人基因组的共有特征(Trinklein等人，Genome Res 14:62,2004)。双向启动子在两个方向上启动转录并且通常含有调控两种基因的共用元件。除了天然双向启动子之外，已经合成了双向的启动子。一种这样的启动子是bi-CMV。pBI-CMV1是一种哺乳动物双向表达载体，其使得感兴趣的两种蛋白能够组成性表达。蛋白质表达由两种组成性型活化的最小人巨细胞病毒启动子(相反取向的PminCMV1和PminCMV2)驱动。双向CMV启动子示的例性的DNA序列为SEQ IDNO.536。
双向启动子(例如，bi-CMV启动子)主要用于实现hIL15和IL-15Rα(或Sushi结构域)的共表达。当两个分子利用IRES或p2A序列共表达时，通常其为hIL15和IL-15Rα(或Sushi结构域)。在这些情况下，可以利用双向启动子或者作为具有IRES或p2A序列的多顺反转录本共表达IL-12和PD-L1阻断肽，或者其可以从它们自己的启动子/调控区单独表达。
可以使用其他启动子。细胞启动子、病毒启动子等是适合的。该启动子可以是组成型的或可诱导的或细胞/组织特异性的。许多启动子是公知的。可以使用的一种特定启动子是组成型EF-1α启动子。
序列被组装在一个或多个表达盒中。实例提供了示例性的一些表达盒的特定版本。可将该表达盒在不会破坏关键功能(例如，复制)的任意位置插入到HSV基因组中。在某些实施方式中，在首次缺失重复区之后在内部或者末端重复区中插入该表达盒。其他适合的插入区域包括在病毒基因之间，例如，UL3和UL4病毒基因之间、UL50和UL51基因之间、以及在US1和US2之间。
在某些实施方式中，在病毒基因(例如，UL3和UL4、UL50和UL51和/或US1和US2)之间插入表达PD-L1阻断肽的表达盒。在其他实施方式中，插入表达IL-12、IL-15和IL-15Rα的表达盒代替该末端重复区以及在UL3和UL4基因之间插入表达PD-L1肽的表达盒。
D.治疗组合物
提供了可以用于预防、治疗或减轻疾病影响的治疗组合物，所述疾病例如，例如，癌症。更具体地，提供了包含至少一种如本文中所述的溶瘤病毒的治疗组合物。代表性实例包括具有一种或多种IL12、IL15和/或IL受体15α亚单位的表达盒的oHSV。在一种实施方式中，该表达盒表达所有IL12、IL15和IL受体15α亚单位。在优选的实施方式中，该表达盒包含鼠或人IL12、hIL15和hIL15受体α亚单位。
在某些实施方式中，该组合物进一步包含可药用载体。短语“可药用载体”意指包含不会干扰溶瘤病毒生物学活性的效力并且对接受给药的受试者无毒的任意溶媒、稀释剂或赋形剂(通常参见Remington:The Science and Practice of Pharmacy,LippincottWilliams&Wilkins；第21版(2005年5月1日and in The United States PharmacopE1A:TheNational Formulary(USP 40–NF 35和增刊)。
在本文中所述的溶瘤病毒的情形下，适合药用的溶媒的非限制性实例包括磷酸盐缓冲盐水溶液、水、乳液(例如油/水乳液)、各种形式的润湿剂、无菌溶液等等。另外的可药用载体包括凝胶、可生物吸收的基质材料、含有溶瘤病毒的植入元件、或任何其他的溶媒、递送剂或者分散装置或材料。这样的溶媒能够通过常规方法配置并且能够以有效剂量向受试者施用。另外的可药用赋形剂包括，但不限于，水、盐水、聚乙二醇、透明质酸和乙醇。其中也可以包括可药用盐，例如，无机酸盐(例如盐酸盐、氢溴酸盐、磷酸盐、硫酸盐等等)和有机酸的盐(例如乙酸盐、丙酸盐、丙二酸盐、苯甲酸盐等等)。可以用于将oHSV递送至靶癌细胞的这样的可药用(药品级)溶媒、稀释剂和赋形剂优选地不会在接受该组合物的个体(受试者)中诱导免疫应答(并且优选地以无不当毒性的方式给药)。
能够以各种不同的浓度提供本文中提供的组合物。例如，所提供的溶瘤病毒的剂量范围可以是约106pfu至约109pfu。在进一步的实施方式中，该治疗的剂量形式范围可以为约106至约108pfu/ml，每2-5周向具有大病灶(例如，>5cm)的患者注射多达4ml以及在具有小病灶(例如，<0.5cm)的患者中住着较小的量(例如，达0.1ml)。
在本发明的某些实施方式中，可以使用低于标准的剂量。因此，在某些实施方式中，可以向患者施用小于约106pfu/ml(每2-3周向患者注射达4ml)。
该组合物可以在有益于稳定货架期的温度下储存，该温度包括室温(约20℃)、4℃、-20℃、-80℃，储存在液氮中。由于预期体内使用的组合物通常不具有防腐剂，因此通常在低温下储存。组合物可以干燥形式(例如，冻干)或液体形式储存。
E.给药
除了本文中红所述的组合物之外，还提供了利用这样的组合物来治疗或缓解癌症的各种方法，包括向受试者施用有效剂量或者有效量的如本文所述HSV载体的步骤。
术语“有效剂量”和“有效量”是指足以影响目标癌症治疗的溶瘤病毒的量，例如，有效减少目标肿瘤尺寸或载荷的量、或者妨碍靶标肿瘤细胞生长速率的量。更具体地，这样的术语是指，以必要剂量和治疗期间施用，有效达到期望结果的溶瘤病毒的量。例如，在治疗癌症的情形中，本文所述组合物的有效量是引起环节、减小肿瘤负荷和/或防止肿瘤扩散或癌症生长的量。有效量可以根据各种因素变化，例如受试者的疾病状态、年龄、性别和体重，以及药物配方、施用途径等等，但能够由本领域技术人员常规地确定。
向诊断患有癌症或疑似患有癌症的受试者施用该治疗组合物。受试者可以是人或非人动物。
该组合物用于治疗癌症。如本文中使用的，术语“治疗”或“处理”意指用于获得有益或期望结果的过程，包括临床结果。有益的或期望的临床结果可以包括，但不限于，可检测的或不可检测的疾病的一种或多种症状或病况的缓解或改善、疾病程度的减轻、疾病的稳定(即，未恶化)状态、防止疾病扩散、延迟或减慢疾病发展、疾病状态的缓解或减轻、疾病复发的减少以及控制(部分或全部)。术语“治疗”和“处理”也可以意指相比于不接受治疗的预期存活期而言，存活期延长。
癌症的代表性形式包括癌(carcinomas)白血病、淋巴瘤、骨髓瘤和肉瘤。进一步的实例包括，但不限于，胆管癌、脑癌(例如，胶质母细胞瘤)、乳腺癌、宫颈癌、结肠直肠癌、CNS癌症(例如，听神经瘤、星形细胞瘤、颅咽管瘤、室管膜瘤(ependymoma)、胶质母细胞瘤、血管母细胞瘤、髓母细胞瘤、网囊瘤、神经母细胞瘤、少突胶质瘤、松果体瘤和视网膜母细胞瘤)、子宫内膜衬(endometrial lining)癌、造血细胞癌(例如，白血病和淋巴瘤)、肾癌、喉癌、肺癌、肝癌、口腔癌、卵巢癌、胰腺癌、前列腺癌、皮肤癌(例如，黑素瘤和鳞状细胞癌)和甲状腺癌。癌症可以包含实体瘤(例如，肉瘤例如纤维肉瘤、粘液肉瘤、脂肪肉瘤、软骨肉瘤和骨肉瘤)、弥漫性癌症(例如，白血病)、或这些的一些组合(例如，同时具有实体瘤和弥漫性或弥散性癌细胞的转移性癌症)。癌症能够对于常规治疗具有抗性(例如，常规化疗和/或放疗)。
也可以治疗良性肿瘤和不希望的细胞增殖的其他病症。
本文中所述的oHSV可以通过如下途径给予，例如，口服、局部、肠胃外、全身、动静脉内、肌内、眼内、鞘内、瘤内、皮下或经皮给药。在某些实施方式中，可以通过套管、通过导管、或通过直接注射递送该溶瘤病毒。施用的部位可以是瘤内或远离肿瘤的位置。施用的途径经常取决于待治疗癌症的类型。
本领域内的主治医师基于患者的表达、患者观察加过和各种临床因素，包括例如受试者体型、体表面积、年龄、性别和所施用的特定溶瘤病毒、施用的时间和途径、待治疗的癌症类型、患者的总体健康状况以及患者经历的其他药物治疗，能够容易地确定溶瘤病毒的最佳或适当剂量方案。根据某些实施方式，利用本文所述溶瘤病毒对受试者进行可以与其他类型的治疗联用，例如化疗，例如，利用化疗剂例如依托泊苷、异环磷酰胺、阿霉素、长春新碱、强力霉素等等。
可将oHSV配制成用于临床应用的药物和药物组合物并且可将其与可药用载体、稀释剂、赋形剂或辅料组合。该配方至少部分地取决于施用的途径。适合的配方可以包含无菌培养基中的病毒和抑制剂。该配方可以是流体、凝胶、贴剂或固体形式。可将配方提供给受试者或者医疗专业人士。
优选地施用治疗有效的量。这是一种足以对受试者显示出益处的用量。所施用的实际用量和给药时程将至少部分地取决于癌症的性质、受试者的情况、递送位点以及其他因素。
在本发明的另外实施方式中，溶瘤病毒可以瘤内施用，或者手术切除肿瘤前后施用。
以下实施例是以举例说明的方式提供，而不是以限制的方式提供。
实施例
所有的构建体均利用标准的重组技术产生，包括化学合成。
实施例1
示例性的OHSV载体的示意图
图1A和图1B提供了代表性oHSV载体的示例性示意图。
实施例2
示例性构建体
在本实施例中，提出了各种构建体及其序列。
hVG001-1-2包含经修饰的ICP34.5区(图2；SEQ ID NO.572)、经修饰的UL54启动子-调控区(图3；SEQ ID NO.573)、在UL3和UL4之间的基因区域中插入PD-L1阻断子(图4；SEQ ID No.574)、以及携带编码IL-12、IL-15和IL-15受体α亚单位的表达盒的经修饰的末端重复(TR)区(图5；SEQ ID NO.575)。所述病毒还具有经修饰的和部分缺失的ICP 34.5区。
除了mVG001-1-2在病毒基因组上的相同位置中携带小鼠版本的IL-12和小鼠PD-L1阻断子之外，mVG001-1-2与人版的hVG001-1-2在功能上完全相同，其中hVG001-1-2携带人IL-12和人PD-L1阻断子。
实施例3
后续实施例中使用的缩写
TF-Fc：融合至Fc并且用于构建VG001-1-2的PD-L1阻断肽(TF)。
IL-TF-Fc：携带IL-12、IL-15和PD-L1阻断子的质粒。
HSV-345：ICP34.5-缺失的病毒。
OS-ICP27 2-11：具有Oct4/Sox2结合位点和在不用于构建VG001-1-2的ICP27(OS-ICP27)的启动子-调控区中插入的surviving启动子(OS)的ICP34.5-缺失的病毒。
OS-ICP27 5-7：具有不用于构建VG001-1-2的OS-ICP27突变的ICP34.5-缺失的病毒。
NO-ICP27 1-4-4(也被称作NO-ICP27-145)：具有NF-kB应答元件和在ICP27的转录起始位点的上游145bp处插入到不用于构建VG001-1-2的ICP27(NO-ICP27)的启动子-调控区中的Oct4/Sox2结合位点(NO)的ICP34.5-缺失的病毒。
NO-ICP27 5-2-2(也被称作NO-ICP27-99)：具有NF-kB应答原件和在ICP27的转录起始位点的上游99bp处插入到不用于构建VG001-1-2的ICP27(NO-ICP27)的启动子-调控区中的Oct4/Sox2结合位点(NO)的ICP34.5-缺失的病毒。
VG001-1.7(也被称作HSV 1-VG 001-1.7)：用于构建VG001-1-2的骨架(backbone)病毒(携带外源启动子且poly(A)侧翼(flank)在病毒基因组的缺失的末端重复区中具有空MCS的NO-ICP27 1-4-4突变体，该病毒基因组的缺失的末端重复区随后被用于插入插入IL-12/IL-15表达盒)。
VG001-15h(也被称作VG001-1-2-15h)：携带人IL-15的VG001。
VG001-1215h(也被称作VG001-1-2-1215h)；携带人IL-12和人IL-15的VG001。
VG001-PLBh(也被称作VG001-1-2-PLBh)：携带插入到UL3和UL4之间的基因间区域中的人PD-L1阻断子的VG001。
8-8-15RA1-PDL1b：携带人IL-15和人PD-L1阻断子的VG001。
VG001-1-2-1215PLBm(也被称作mVG001-1-2)：携带小鼠IL-12、人IL-15和小鼠PD-L1阻断子的VG001。
VG001-1-2-1215PLBh(也被称作hVG001-1-2或VG001-1-2)：携带人IL-12、人IL-15和人PD-L1阻断子的VG001。
实施例4
细胞被HVG001-1-2感染后IL-12的表达
在本实施例中，示出了IL-12表达的蛋白质印迹分析和ELISA表达。
图6A示出了VG001-1-2-1215PLBh病毒感染的蛋白质印迹分析结果。用VG001-1-2-1215PLB或VG001-1.7病毒(MOI＝1)感染H460肿瘤细胞24小时。制备细胞裂解液，上样至12％SDS-PAGE凝胶，并将其转移至PVDF膜。用抗-人IL-12抗体对该膜进行印记分析，之后通过HRP-缀合的抗-小鼠IgG二抗进行分析，并利用Bio-Rad ImageLab系统检测和分析图像。
图6B-图6C示出了VG001-1-2-1215PLBh病毒感染后人IL-12的产生上调。用VG001-1-2-1215PLB或VG001-1.7病毒(MOI＝1)感染LS174T或H460肿瘤细胞48小时。收获感染的细胞上清并将其结合至涂覆有抗-人IL-12捕获抗体的96-孔Immuno Maxisorp平底板。经由生物素化的抗-人IL-12抗体、亲和素-辣根过氧化物酶(HRP)、和3,3’,5,5’-四甲基联苯胺(TMB)底物检测结合。利用读板器在450nm处收集吸光度测量结果。基于人IL-12标准曲线计算经培养的上清中人IL-12的浓度。
实施例5
细胞被HVG001-1-2感染后IL-15的表达
在本实施例中，示出了IL-15表达的蛋白质印迹分析和ELISA表达。
图7A示出了VG001-1-2-1215PLBh病毒感染后的蛋白质印迹分析结果。用VG001-1-2-1215PLB或VG001-1.7病毒(MOI＝1)感染H460肿瘤细胞24小时。制备细胞裂解液，上样至12％SDS-PAGE凝胶，并将其转移至PVDF膜。用抗-人IL-15抗体对该膜进行印记分析，之后通过HRP-缀合的抗-小鼠IgG二抗进行分析，并利用Bio-Rad ImageLab系统检测和分析图像。
图7B-图7C示出了VG001-1-2-1215PLBh病毒感染后人IL-15产生被上调。用VG001-1-2-1215PLB或VG001-1.7病毒(MOI＝1)感染LS174T或H460肿瘤细胞48小时。收获感染的细胞上清并结合于涂覆有抗-人IL-15捕获抗体的96-孔Immuno Maxisorp平底板。经由生物素化的抗-人IL-15抗体、亲和素-辣根过氧化物酶(HRP)和3,3’,5,5’-四甲基联苯胺(TMB)底物检测结合。利用读板器在450nm处收集吸光度测量结果。基于人IL-15标准曲线计算经培养的上清中人IL-15的浓度。
实施例6
细胞被HVG001-1-2感染后IL-4的表达
在本实施例中，示出了IgG4表达的蛋白质印迹分析和ELISA表达。
图8A示出了VG001-1-2-1215PLBh病毒感染后的蛋白质印迹分析结果。用VG001-1-2-1215PLB或VG001-1.7病毒(MOI＝1)感染H460肿瘤细胞24小时。制备细胞裂解液，上样至12％SDS-PAGE凝胶，并将其转移至PVDF膜。用HRP-缀合的抗-人IgG抗体对膜进行印记分析，并利用Bio-Rad ImageLab系统检测和分析图像。
图8B-图8C示出了VG001-1-2-1215PLBh病毒感染后人PD-L1阻断子(融合至人Fc区)产生被上调。用VG001-1-2-1215PLB或VG001-1.7病毒(MOI＝1)感染LS174T或H460肿瘤细胞48小时。收获感染的细胞上清并结合于涂覆有抗-人IgG4捕获抗体的96-孔ImmunoMaxisorp平底板。经由生物素化的抗-人IgG4抗体、亲和素-辣根过氧化物酶(HRP)、和3,3’,5,5’-四甲基联苯胺(TMB)底物检测结合。利用读板器在450nm处收集吸光度测量结果。基于人IL-4标准曲线计算经培养的上清中人IL-4的浓度。
实施例7
包含PD-L1阻断肽的构建体
用Igκ链先导序列(SEQ ID NO:501)产生PD-L1阻断肽。当同一构建体中具有两种或更多种阻断肽时，将其与富含Gly-Ser的序列(Gly4Ser)3(SEQ ID NO:503)连接。制备以下构建体。
仅TF：METDTLLLWVLLLWVPGSTGTAHPSPSPRSAGQF(SEQ ID NO:537)；
ET+TF：METDTLLLWVLLLWVPGSTGEYRMSPSNQTGGGGSGGGGSGGGGSTAHPSPSPRSAGQF(SEQID NO:538)；
YT+TF：METDTLLLWVLLLWVPGSTGYYRMSPSNQTGGGGSGGGGSGGGGSTAHPSPSPRSAGQF(SEQID NO:539)；
小鼠TF：METDTLLLWVLLLWVPGSTGTRYPSPSPKPEGRF(SEQ ID NO:540)；
小鼠WT+TF：METDTLLLWVLLLWVPGSTGWNRLSPSNQTGGGGSGGGGSGGGGSTRYPSPSPKPEGRF(SEQ ID NO:541)。
Triple TF+ET：METDTLLLWVLLLWVPGSTGTAHPSPSPRSAGQFTAHPSPSPRSAGQFTAHPSPSPRSAGQFGGGGSGGGGSGGGGSEYRMSPSNQTEYRMSPSNQTEYRMSPSNQT(SEQ ID NO:542)
METDTLLLWVLLLWVPGSTGEYRMSPSNQTEYRMSPSNQTEYRMSPSNQTGGGGSGGGGSGGGGSTAHPSPSPRSAGQFTAHPSPSPRSAGQFTAHPSPSPRSAGQF(SEQ ID NO:543)。
利用IL-2信号序列(MYRMQLLSCIALSLALVTNS(SEQ ID NO:502)、和人IgG4 Fc区(具有铰链区)(SEQ ID NO:544)或鼠IgG1 Fc区(具有铰链区)(SEQ ID NO:545)来制备其他的构建体。该构建体为：
仅TF：MYRMQLLSCIALSLALVTNSTAHPSPSPRSAGQFISAMVRSPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSPGK(SEQ ID NO:546)
ET+TF：MYRMQLLSCIALSLALVTNSEYRMSPSNQTGGGGSGGGGSGGGGSTAHPSPSPRSAGQFISAMVRSPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSPGK(SEQ ID NO:547)
YT+TF：MYRMQLLSCIALSLALVTNSYYRMSPSNQTGGGGSGGGGSGGGGSTAHPSPSPRSAGQFISAMVRSPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSPGK(SEQ ID NO:548)
小鼠TF：MYRMQLLSCIALSLALVTNSTRYPSPSPKPEGRFISAMVRSGCKPCICTVPEVSSVFIFPPKPKDVLTITLTPKVTCVVVDISKDDPEVQFSWFVDDVEVHTAQTQPREEQFNSTFRSVSELPIMHQDWLNGKEFKCRVNSAAFPAPIEKTISKTKGRPKAPQVYTIPPPKEQMAKDKVSLTCMITDFFPEDITVEWQWNGQPAENYKNTQPIMDTDGSYFVYSKLNVQKSNWEAGNTFTCSVLHEGLHNHHTEKSLSHSPGK(SEQ ID NO:549)
小鼠WT+TF：MYRMQLLSCIALSLALVTNSWNRLSPSNQTGGGGSGGGGSGGGGSTRYPSPSPKPEGRFISAMVRSGCKPCICTVPEVSSVFIFPPKPKDVLTITLTPKVTCVVVDISKDDPEVQFSWFVDDVEVHTAQTQPREEQFNSTFRSVSELPIMHQDWLNGKEFKCRVNSAAFPAPIEKTISKTKGRPKAPQVYTIPPPKEQMAKDKVSLTCMITDFFPEDITVEWQWNGQPAENYKNTQPIMDTDGSYFVYSKLNVQKSNWEAGNTFTCSVLHEGLHNHHTEKSLSHSPGK(SEQ ID NO:550)。
实施例8
在双向CMV启动子的控制下包含IL-15和IL-15Rα的构建体
在本实施例中，产生了各种构建体以在双向CMV启动子的控制下共表达IL-15和IL-15Rα。
在构建体1中，bi-CMV启动子驱动IL-15Rα和IL-15的Sushi结构域的表达(图9，SEQID No.557)。
在构建体2中，bi-CMV启动子驱动IL-15和IL-15Rα变体4的表达(图10，SEQ IDNo.558)。
在构建体3中，bi-CMV启动子驱动IL-15-K5和IL-15RαSushi结构域-E5的表达(图11，SEQ ID No.559)。
在构建体4中，bi-CMV启动子驱动IL-15-K5和IL-15Rα变体4-E5的表达(图12，SEQID No.560)。
实施例9
在EF1α启动子控制下包含IL-15和IL-15Rα基因的构建体
在本实施例中，产生各种构建体以在EF1α启动子(SEQ ID NO:551)的控制下在多顺反子转录本中表达IL-15和IL-15Rα。IL-15和IL-15Rα通过示例性IRES序列(SEQ ID NO:552)连接。
在构建体1中，EF1α启动子控制IL-15-IRES-IL-15RαSushi结构域的表达(图13，SEQ ID No.561)。
在构建体2中，EF1α启动子控制IL-15-IRES-IL-15Rα变体4的表达(图14，SEQ IDNo.562)。
在构建体3中，EF1α启动子控制IL-15K5-IRES-IL-15RαSushi结构域E5的表达(图15，SEQ ID No.563)。
在构建体4中，EF1α启动子控制IL-15K5-IRES-IL-15Rα变体4E5的表达(图16，SEQID No.564)。
实施例10
在CMV启动子的控制下包含IL-12、IL-15和IL-15Rα基因的构建体
在本实施例中，产生各种构建体以在CMV启动子的控制下在多顺反子转录本中表达IL-12、IL-15和IL-15Rα。IL-12、IL-15和IL-15Rα通过示例性的p2A序列(SEQ ID NO:554)连接。
在构建体1中，CMV启动子(SEQ ID NO:553)控制IL-12-p2A-IL-15-p2A-IL-15RαSushi结构域的表达(图17，SEQ ID Nos.565,569)。
在构建体2中，CMV启动子控制IL-12-p2A-IL-15-p2A-IL-15Rα变体1的表达(图18，SEQ ID Nos.566,570)。
在构建体3中，CMV启动控制IL-12-p2A-IL-15K5-p2A-IL-15RαSushi结构域E5的表达(图19，SEQ ID Nos.567,571)。
在构建体4中，CMV启动子控制IL-12-p2A-IL-15K5-IRES-IL-15Rα变体1E5的表达(图20，SEQ ID Nos.568,572)。
实施例11
插入到UL3和UL4之间的包含PD-L1阻断子的构建体
在本实施例中，产生构建体以在碱基829和830之间的基因间区域中表达PD-L1阻断肽。在SEQ ID NO:556中，碱基1-675:UL3编码序列；碱基676-829:UL3和UL4之间的区域和PD-L1阻断子盒的上游；碱基830-833:UL3和UL4之间的区域PD-L1阻断子盒的下游；碱基834-1433:UL4编码序列。
实施例12
通过阻断肽抑制人PD-L1结合于PD-1
在4℃将重组体人PD-L1 Fc蛋白涂覆于96-孔平底板的底部过夜。在涂覆板过夜之后，向板的每个孔中加入不同PD-L1阻断子并在室温下孵育2小时，之后加入重组体人PD-1Fc蛋白。随后将生物素化的抗-人IgG抗体和和链霉亲和素-HRP加入到每个孔中，并且通过加入TMB底物来检测人PD-1与PD-L1的结合。通过微读板器在450nm波长处测量显色。通过与非合成的肽对照来计算抑制百分比。图21示出了肽ET、ET+TF、YT、YT+TF、TW、TW+TF、WT、WT+TF和TF以两种不同浓度(3μM和10μM)产生的百分比抑制。在10μM时，抑制范围为约22％至约48％。
实施例13
通过阻断肽结合的阻断PD-L1增强针对肿瘤细胞的细胞毒性
用抗-CD3抗体+人IL-2刺激人外周血单核细胞(PBMC)24小时并且随后与不同的合成PD-L1阻断子和钙黄绿素-AM标记的靶细胞一起孵育4小时。孵育4小时后收获经培养上清的细胞，并且通过微读板器测量释放的钙黄绿素-AM荧光。基于下式计算细胞毒性的百分比：[(样品读数–最小释放)/(最大释放–最小释放)]×100。
图22A-图22B示出了四种不同肿瘤细胞的结果：H460、U87、LS147T和MDA-MB-231细胞。在一些肿瘤细胞上，除了TF之外针对所有肽的细胞毒性统计学显著增加。
实施例14
IL-12和IL-15在细胞因子产生方面的协同效应
人PBMC与培养基对照、仅IL-12、仅IL-15RA、或组合的IL-12、IL-15和IL-15Rα1+中和抗-IL-12或抗-IL-15抗体一起孵育48小时。收获经培养的细胞上清用于通过ELISA测定人IFNγ和TNFα的产生。
图23A和图23B示出了细胞因子产生的结果。IL-12和IL-15Rα1组合导致细胞因子人IFNγ和TNFα的统计学显著增加。抗-IL-12抗体抑制其产生。
实施例15
IL-12和IL-15针对肿瘤细胞在细胞毒性方面的协同效应
人PBMC与肿瘤靶细胞以及培养基对照，仅IL-12，仅IL-15RA，或组合的IL-12、IL-15和IL-15RA1+中和抗-IL-12或抗-IL-15抗体一起孵育24小时。收获经培养的细胞上清用于通过LDH测量细胞毒性。基于下式计算细胞毒性的百分比：[(样品读数–最小释放)/(最大释放–最小释放)]×100。
图24A和图24B示出了IL-12和IL-15一起以统计学显著的方式增加细胞毒性。在MDA-MB-231细胞系上，添加抗-IL-12或IL-15抗体显著减少该效应。
实施例16
病毒VG001-1-2-PLBH和VG001-1-2-15H的体外效力
在本实施例中，将3×104个H460或LS174T肿瘤细胞接种在至96孔板的每个孔中，并在37℃培养过夜。第二天，用VG001-1.7backbone、VG001-1-2-PLBh或VG001-1-2-15h病毒(MOI＝1)感染接种的细胞24小时，并且评估人IL-12、人IL-15和人IgG4的产生(图25A-C)。随后将3×105人个PBMC加入到培养物中并且共培养24小时以通过LDH测定来评估细胞毒性(图25D)或者共培养48小时以通过ELISA评估人IFNg产生(图25E)。对于细胞毒性测定，基于下式计算细胞毒性的百分比：[(实际读数–最小释放)/(最大释放–最小释放)]×100％。收获自仅与培养基一起孵育的肿瘤细胞的上清用作最小释放，而收获自与裂解缓冲液一起孵育的肿瘤细胞的上清用作最大释放。
实施例17
各种构建体的体外效力
图26A-图26D示出了各种构建体的体外测定的结果。
图26A-图26B示出了用携带IL-12、IL-15和PD-L1阻断子的IL-TF-Fc质粒转染细胞的结果。在图26A-图26B中，用IL-TF-Fc质粒DNA转染不同的肿瘤细胞系24小时，并且随后将人PBMC加入到培养物中。24小时后收获细胞上清以用于通过LDH测定定量分析细胞毒性(图26A)，并且在48小时后用于通过ELISA测定来检测人IFNg产生(图26B)。
图26C-图26D示出了用各种包括hVG001-1-2的突变体病毒感染细胞的结果。病毒编码的IL12、IL15和PD-L1阻断子协同地增加IFNg产生和细胞毒性。将H460肿瘤细胞接种到96孔板的每一个孔中并在37℃培养过夜。第二天，用指定病毒以MOI＝1感染接种的细胞24小时。随后将人PBMC加入到培养物中并且共孵育24小时以通过LDH测定评估细胞毒性(图26C)，或者共孵育48小时以通过ELISA评估人IFNg产生(图26D)。对于细胞毒性测定，基于下式计算细胞毒性的百分比：[(实际读数–最小释放)/(最大释放–最小释放)]×100％。收获自仅与培养基一起孵育的肿瘤细胞的上清用作最小释放，而收获自与裂解缓冲液一起孵育的肿瘤细胞的上清用作最大释放。
在图27A-图27E中，用VG001-1-2-1212PLBh(VG001-1-2h)和HSV-345病毒以MOI 0、0.04、0.2、1和5感染一组9种不同的人肿瘤细胞系(+Vero细胞)。利用MTT测定在感染后48小时定量分析细胞活力。
图28A-图28J示出了各种构建体的体外测定的结果。图28A-图28E示出了在小鼠肿瘤细胞系和Vero细胞系上进行的mVG001-1-2和HSV-345的细胞活力测定的结果；图28F-图28J示出了在CT26小鼠肿瘤细胞感染mVG001-1-2或VG001-1.7之后的转基因表达的表征。
在图28A-图28E中，用VG001-1-2m和HSV-345病毒以MOI 0、0.04、0.2、1和5感染一组6只不同小鼠肿瘤细胞系(+Vero细胞)。在感染后48小时，利用MTT测定定量分析细胞活力。
在图28F-图28J中，将3×104个CT26肿瘤细胞接种到96孔板的每个孔中，并在37℃培养过夜。第二天，用VG001-1.7backbone或VG001-1-2-1215PLBm病毒(MOI＝1)感染接种的细胞24小时，并且评估小鼠IL-12、人IL-15、和小鼠IgG的产生。随后将来自Balb/c小鼠的3×105个脾细胞加入到培养物中并且共培养24小时，以通过LDH测定评估细胞毒性或者共培养48小时以通过ELISA评估小鼠IFNg产生。对于细胞毒性测定，基于下式计算细胞毒性：[(实际读数–最小释放)/(最大释放–最小释放)]×100％。收获自仅与培养基一起孵育的肿瘤细胞的上清用作最小释放，而收获自与裂解缓冲液一起孵育的肿瘤细胞的上清用作最大释放。
在图29A-图29E中，将3×104个H460、LS174T或UMUC3肿瘤细胞接种到96孔板的每个孔中，并在37℃培养过夜。第二天，用VG001-1.7backbone和VG001-1-2-1215h病毒(MOI＝1)感染接种的细胞24小时并测量人IL-12、人IL-15和人IgG4的产生(18R)。随后将3×105个人BMC加入到培养物中，并且共培养24小时以通过LDH测定评估细胞毒性(18S)或者共培养48小时通过ELISA评估人IFNγ产生(18T)。对于细胞毒性测定，基于下式计算细胞毒性的百分比：[(实际读数–最小释放)/(最大释放–最小释放)]×100％。收获自仅与培养基一起孵育的肿瘤细胞的上清用作最小释放，而收获自与裂解缓冲液一起孵育的肿瘤细胞的上清用作最大释放。
在图30A-图30G中，在感染后72小时且MOI为0至5的条件下，在各种人类癌细胞(包括U87、MCF7、H460、LNCaP、LS174T、MDA、和PC3)中评估VG001-1-2-1215PLBh(hVG001-1-2)病毒的抗肿瘤效果。通过MTT测定定量分析细胞存活百分比。在所测定的全部人肿瘤细胞系中，VG001-1-2-1215PLBh病毒表现出强力的T细胞杀伤能力。
实施例18
VG001-1-2病毒构建体的体内效力
在图31A-图31B中，对A20鼠B-细胞淋巴瘤肿瘤荷瘤BALB/c小鼠进行5次瘤内注射总共1×107PFU/小鼠的VG001-1-2-1215PLBm(mVG001-1-2)病毒或VG001-1.7backbone病毒或用PBS(载体对照)注射。在指定次数注射后进行肿瘤尺寸测量。相比于用PBS处理的小鼠，用VG001-1-2-1215PLBm处理的小鼠表现出肿瘤体积的显著(P<0.05)减小。
在图31C-图31D中，向CT26鼠结肠癌荷瘤BALB/c小鼠进行5次瘤内注射总共5×106PFU/小鼠的VG001-1-2-1215PLBm(mVG001-1-2)病毒或VG001-1.7backbone病毒或用PBS(载体对照)注射。在指定次数注射后进行肿瘤尺寸测量。相比于用PBS处理的小鼠，用VG001-1-2-1215PLBm处理的小鼠表现出肿瘤体积的显著(P<0.05)减小。
在图31E-图31G中，评估了小鼠中异种移植人前列腺肿瘤的oHSV治疗。在十二只小鼠的右侧下腹部移植LNCaP人前列腺肿瘤细胞。移植后35天，随机选择组的6只动物两次瘤内注射总共5×107PFU/小鼠的VG001-1-2-1215PLBh(hVG001-1-2)病毒，而其余6只动物作为载体对照并且两次注射相等体积的PBS。利用两种不同方法测量肿瘤尺寸。卡尺测量表示为，相比于病毒或PBS时的肿瘤体积，在给定时间点肿瘤体积的倍数变化(图31E)。在研究期间，用VG001-1-2-1215PLBh病毒处理的荷瘤小鼠表现出明显的肿瘤萎缩，在15天结束时肿瘤尺寸减小超过50％，而在相同时间段内用载体处理的小鼠显示出肿瘤体积的大约3倍增加。还利用全动物生物发光成像系统(IVIS Imaging System；Xenogen,Mountain View,CA)监测了肿瘤生长。对信号强度进行定量分析，作为每秒检测到的所有光子的总和(图31F)。相比于PBS处理的对照，利用IVIS的肿瘤生长的定量成像示出了用oHSV处理的动物中肿瘤尺寸的甚至更显著减小，肿瘤移植后50天利用荧光沉降至不可检测水平(图31G；左侧为两只载体对照，右侧为两只oHSV-处理的小鼠)。
实施例19
HVG001-1-2在细胞系中的复制
图32A-图32C、图33A-图33D和图34A-图34E中的生长曲线和细胞毒性表达示出了hVG001-1-2病毒复制以及亲代HSV-345病毒。这些表达还示出了，相比于人细胞系，该病毒在小鼠肿瘤细胞系中也不生长，但已知HSV-1在小鼠细胞中生长不良。
实施例20
病毒改性的评估
仅用培养基、仅用重组体IL-12、仅用重组体IL-15、或者用具有或不具有抗-IL-12(6mg/ml)或抗-IL-15(0.5mg/ml)中和抗体的IL-12+不同形式的IL-15/IL-15RA1复合物刺激人PBMC48小时。随后针对人IFNg收获经培养的上清并且如图35A和图35B中所示利用ELISA测定人TNFa产生。
为了评估针对肿瘤细胞的细胞毒性，将钙黄绿素-AM-标记的肿瘤细胞与经刺激的人PBMC共同孵育24小时。收获上清以用于测量释放的荧光。将从钙黄绿素-标记的肿瘤细胞收获的上清与仅用作最小释放的培养基一起孵育，并且将收获自钙黄绿素-标记的肿瘤细胞的上清与用作最大释放的裂解缓冲液一起孵育。基于下式计算细胞毒性百分比：[(实际读数–最小释放)/(最大释放–最小释放)]×100％。图35C中示出了U87肿瘤细胞的细胞毒性结果，图35D中示出了MDA-MB-231肿瘤细胞的细胞毒性结果。
实施例21
体外有效表达
仅用培养基、仅用重组体IL-12、仅用重组体IL-15、或者用具有或不具有抗-IL-12(6mg/ml)或抗-IL-15(0.5mg/ml)中和抗体的IL-1+IL-15/IL-15RA1复合物刺激人外周血单核细胞(PBMCs)48小时。随后收获经培养的上清用于人IFNg和人TNFa产生，如图36A和图36B中所示利用ELISA测定。
为了评估针对肿瘤细胞的细胞毒性，将1×104个钙黄绿素-AM-标记的肿瘤细胞与1×105个刺激的人PBMC共同孵育24小时。收获上清用于测量释放的荧光。将收获自钙黄绿素-标记的肿瘤细胞的上清与用作最小释放的培养基一起孵育，收获自钙黄绿素-标记的肿瘤细胞的上清与用作最大释放的裂解缓冲液一起孵育。.基于下式计算细胞毒性百分比：[(实际读数–最小释放)/(最大释放–最小释放)]×100％。图36C示出了U87肿瘤细胞的细胞毒性结果，图36D示出了MDA-MB-231肿瘤细胞的结果。
实施例22
感染VG001-1-2h的肿瘤细胞产生人IL-12、人IL-15/IL15Ra和人IgG4
简言之，将LNCaP细胞移植到裸鼠中并接受溶媒、ICP27-、或VG001-1-2h病毒的注射。在注射后120小时收获血清和肿瘤样品，并通过ELISA评价人IL-12、人IL-15/IL-15Ra和人IgG4的产生。图37A中示出了结果。
将Fadu细胞移植到裸鼠中并接受溶媒、HSV 1-VG 001-1.7或VG001-1-2h病毒注射。在注射后24小时收获肿瘤样品，并通过ELISA评价人IL-12、人IL-15/IL-15Ra和人IgG4产生。图37B中示出了结果。
实施例23
VG001-1-2m在免疫应答中的效果
将CT26结肠癌细胞植入到balb/c小鼠中并接受PBS、HSV 1-VG 001-1.7或VG001-1-2m病毒注射。在注射后24小时收获肿瘤细胞，并通过流式细胞计来测量CD8+T细胞、CD4+T细胞、或NK细胞的百分比。图38A-图38C中示出了结果。
实施例24
另一种示例性构建体
在本实施例中，对构建体进行进一步改造，特别是对位于IL12-IL15-IL15RA1表达盒侧翼的US12(ICP47)启动子区域进行改造，从而提出了另一种构建体及其序列。
VG001-1-2包含经修饰的ICP34.5区(图40；SEQ ID NO.599)、经修饰的UL54启动子-调控区(图41；SEQ ID NO.596)、在UL3和UL4之间的基因区域中插入PD-L1阻断子(图42；SEQ ID No.589)、以及携带编码IL-12、IL-15和IL-15受体α亚单位(IL12-IL15-IL15RA1)的表达盒的经修饰的末端重复(TR)区(图43；SEQ ID NO.576)。IL12-IL15-IL15RA1表达盒所表达的蛋白序列为SEQ ID No.577。SEQ ID No.578-582分别为IL12、IL15、IL15RA1、自剪切连接肽P2A上游、自剪切连接肽P2A的序列。
VG001-1-2携带人IL-12和人PD-L1阻断子。mVG001-1-2为相应的小鼠版本，与VG001-1-2相比，mVG001-1-2除了在病毒基因组上的相同位置中携带的是小鼠版本的IL-12和小鼠版本的PD-L1阻断子之外，在功能上与VG001-1-2完全相同。
对VG001-1-2携带的IL12-IL15-IL15RA1表达盒侧翼的US12(ICP47)启动子区域进行改造，构建多种侧翼US12(ICP47)启动子的版本：短(short,S；SEQ ID No.583)、中(medium,M；SEQ ID No.584)、长(long,L；SEQ ID No.585)、survivin(SEQ ID No.586)等版本，根据侧翼ICP47启动子版本的不同，相应的VG001-1-2可具体分为VG001-1-2(S)、VG001-1-2(M)、VG001-1-2(L)、VG001-1-2(surviving)等版本。在随后的实施例中，除非另有说明，VG001-1-2是指VG001-1-2(M)，即载体携带的IL12-IL15-IL15RA1表达盒侧翼具有中(M)版本ICP47启动子。VG001-1-2载体的结构示于图70。
实施例25
VG001-1-2的细胞毒性
如图56A所示，用VG001-1-2病毒(MOI为0、0.04、0.2、1、5)感染U87、H460、MCF-7、LS174T和MDA-MB-231等人癌细胞单层，感染后72小时通过MTT测定法对细胞存活百分比进行定量，以评价VG001-1-2的细胞毒性。如图56B所示，用mVG001-1-2病毒(MOI为0、0.04、0.2、1、5)感染四种小鼠肿瘤细胞系B16-F10、4T1、CT26和A20，感染后72小时通过MTT测定法对细胞活力进行定量。
实施例26
VG001-1-2表达的IL12、IL15和PD-L1阻断子的体外表征
如图57所示，用VG001-1-2或其骨架病毒HSV 1-VG 001-1.7(MOI＝1)感染H460人肺癌细胞和LS174T结肠癌细胞24小时。通过免疫印迹(左栏)和ELISA(右栏)定量转基因表达。图57A示出人IL-2的表达，图57B示出人IL-5的表达，图57C示出PD-L1阻断子的表达。
实施例27
VG001-1-2表达的PD-L1阻断子的体外表征
如图58所示，将从VG001-1-2感染的293FT细胞收获的含TF+Fc肽的上清液与重组人PD-1Fc混合，并与人PD-L1 Fc包被的96孔Immuno Maxisorp平底板结合。通过生物素化的抗PD-1抗体、链霉抗生物素蛋白-辣根过氧化物酶(HRP)和3,3'，5,5'-四甲基联苯胺(TMB)底物检测结合。用读板器在450nm收集吸光度测量值。将人PD-1/PD-L1抑制的增加百分比(％)与无肽样品进行比较。
实施例28
VG001-1-2表达的IL12的体外表征
图59示出TF+Fc肽处理的基于细胞的测定结果。用1μg/ml的PHA和50ng/ml的PMA活化5×104个Jurkat T细胞，并与1×105个表达PD-L1的肿瘤细胞一起，与含有PD-L1阻断肽的上清液混合，在37℃下培育48小时。48小时后，收获细胞培养物上清液，通过IL-2ELISA测定Jurkat T细胞产生的IL-2。
实施例29
IL-12、IL-15/IL-15RA和PD-L1阻断子协同增强免疫细胞功能
用人PBMC处理过表达IL12、IL15/IL15RA或共表达IL12和IL15/IL15RA的U87人神经胶质瘤细胞和MDA-MB-231人乳腺癌细胞。
图60A示出通过ELISA测定细胞因子IFN-γ和TNF-α的产生。
图60B示出通过LDH测定免疫细胞诱导的细胞毒性。
图60C示出通过病毒编码的IL12，IL15和PD-L1阻断剂协同实现PBMC活化：将H460肿瘤细胞接种到96孔板的每个孔中，并在37℃下培养过夜，然后用MOI＝1的VG001-1-2病毒感染24小时，并与人PBMC共孵育48小时。通过ELISA定量IFN-γ的产生。测试的病毒包括HSV1-VG 001-1.7(无免疫调节剂)，HSV 1-VG001-1.7-PDL1b(PD-L1阻断子)，HSV 1-VG 001-1.7-15RA1(IL15/IL15RA)，HSV 1-VG 001-1.7-RA1-PDL1b(IL15/IL15RA+PD-L1阻断子)，HSV 1-VG001-1.7-h1215(IL12)+IL15/IL15RA)和VG001-1-2(IL12+IL15/IL15RA+PD-L1阻断子)。
图60D示出将PHA活化的人PBMC(n＝4)与重组人PD-L1蛋白和来自VG001-1-2感染细胞的上清液共温育48小时。IL-1和/或IL15的抗体介导的中和与PD-L1阻断剂的耗尽一起进行。与来自未感染细胞的上清液共孵育用作阴性对照。通过ELISA评估人IFN-γ的产生。
实施例30
VG001-1-2肿瘤内接种的体内功效
图61A示出VG001-1-2在U87人胶质母细胞瘤模型中的功效：将U87细胞植入7只裸鼠的下胁腹，然后以2天的间隔两次瘤内注射1×107PFU/小鼠的VG001-1-2或载体对照。
图61B示出免疫介导的非注射远端肿瘤的远隔清除：将A20细胞植入免疫活性小鼠的胁腹两侧。将mVG001-1-2或HSV 1-VG 001-1.7骨架病毒以5×106PFU/小鼠/天的剂量连续5天注射到仅一侧的肿瘤中。用mVG001-1-2处理16只小鼠，用HSV1-VG 001-1.7处理6只小鼠。与0/6的HSV 1-VG 001-1.7处理的小鼠相比，6/16的mVG001-1-2处理的小鼠在两侧都经历完全肿瘤消退。
图61C示出用mVG001-1-2处理的小鼠受到保护，免于CT26肿瘤再攻击：将CT26细胞植入16只免疫活性BALB/C小鼠的下胁腹，其中8只动物随机分配到mVG001-1-2治疗组，另外8只动物分配到载体对照组。在肿瘤植入后21天，所有8只载体对照动物死于肿瘤负荷。mVG001-1-2处理组中没有动物死于肿瘤，但由于非肿瘤相关病症，该组中的4只动物死亡。mVG001-1-2处理组中存活的4只小鼠在注射后90天在相同位置重新植入CT26细胞。
图61D示出与未用mVG001-1-2处理的年龄匹配的对照小鼠相比，在mVG001-1-2处理的动物中CT26再攻毒后7天的肿瘤大小。
实施例31
用MVG001-1-2处理的肿瘤中的基因表达和T细胞活性
如图62所示，向BALB/c小鼠植入CT26肿瘤细胞，然后连续5天以5×106PFU/小鼠/天的剂量多次注射mVG001-1-2、HSV 1-VG 001-1.7或PBS对照。对注射后第5、7和9天收集的脾细胞进行小鼠IFN-γELISpot测定。定量结果绘制在右图中，每组2只小鼠。
实施例32
MVG001-1-2处理对肿瘤内淋巴细胞群的影响
如图63A所示，BALB/c小鼠接受CT26细胞植入，8天后分5次注射PBS、HSV1-VG 001-1.7骨架或mVG001-1-2病毒。最后一次注射后24或120小时收获肿瘤。通过流式细胞术分析肿瘤块内不同T细胞亚群(图63B)和免疫抑制细胞(图63C)的百分比。图63D示出用针对CD3和穿孔素的单克隆抗体和针对HSV-1的多克隆抗体，对切下的以PBS对照(载体)或mVG001-1-2处理的CT26肿瘤切片进行免疫组织化学分析。
实施例33
最小剂量人IL12或人IL15/IL15RA对免疫细胞功能的影响
如图64所示，将从转染的293FT细胞上清液中收获的人IL-12与PHA刺激的人PBMC共培养48小时。通过ELISA评估人IFN-γ产生。如图64B所示，用表达人IL12或人IL15/IL15RA的质粒转染293FT细胞48小时，收获上清液并与PHA刺激的人PBMC共培养48小时，通过MTT测定评估细胞增殖。
实施例34
病毒的生物分布
如图65A、图65B所示，对携带LS174T肿瘤的裸鼠以5×107PFU/小鼠/天的剂量进行VG001-1-2的肿瘤内注射。在不同时间点对小鼠实施安乐死，并从这些器官中分离基因组DNA，进行qPCR，用IL15RA1基因定量病毒拷贝数。
实施例35
qPCR测量
将小鼠CT26肿瘤细胞植入小鼠中，通过每天注射mVG001-1-2、对照病毒HSV1-VG001-1.7(共5×107pfu)或PBS进行5次处理。在最后一次病毒注射后24和48小时收获肿瘤，分离并纯化RNA，然后使用来自Qiagen的Mouse Innate&Adaptive Immune ResponsesR RT2Profiler TM PCR Array进行基因表达谱分析。如图66所示，与用HSV 1-VG 001-1.7和PBS处理的肿瘤相比，用mVG001-1-2处理的肿瘤中先天性和适应性免疫相关基因的差异表达。通过RT-qPCR验证指定靶标的过表达。
实施例36
感染不同结构的病毒的细胞感染表面MHC的变化
为了解经过启动子改造的VG001-1-2病毒对细胞的影响，分别用VG001-1-2和野生型(VG001-1-2-1215PLBh，ICP47启动子未经改造)病毒以相同的条件感染细胞。
具体而言：将293T细胞铺在6孔板中(1×106细胞/孔)，以加入了10％血清的DMEM培养液培养。待细胞长成单层后，每孔分别加入1×106pfu(MOI＝1)的下列病毒或空白培养液：
a.VG001-1-2病毒(2个孔)
b.野生型病毒(2个孔)
c.只加培养液的不感染对照(2个孔)
病毒感染后将细胞培养过夜，然后以750ul胰蛋白酶消化细胞，加入1ml DMEM,并转移细胞置于流式细胞管，将细胞离心(1500RPM,5min)，去除上清后用2ml PBS洗涤细胞，重复洗涤一次，去除PBS。上述a-c三组各有1孔加入抗MHC(组织相容性复合体)蛋白的抗体(Anti-Hu HLA-ABC):用100ul PBS+2％FBS悬浮细胞，加入2ul抗体。另外各1孔加100ul PBS+2％FBS，不加抗体。在黑暗中孵育1小时，去除抗体，用3ml PBS+2％FBS洗涤细胞，离心细胞(1500RPM,5min)，弃去大部分细胞洗涤液后进行流式细胞分析。结果见图67。
由图67可见，野生型HSV-1病毒感染造成细胞表面MHC蛋白表达量有所降低减。出乎意料的是，感染VG001-1-2病毒的细胞，其MHC表达水平甚至更进一步低于感染野生型HSV-1病毒的细胞。由此可见，相比于野生型病毒，通过改造ICP47启动子，VG001-1-2病毒在感染细胞后能够在更长时间存在于被感染的细胞中躲避免疫细胞攻击，从而可以更好地复制与表达外源基因。
实施例37溶瘤病毒稳定剂的探索性试验
为了优化保存溶瘤病毒的介质，对不同配方的介质进行测试。制备一批VG001-1-2病毒样品，按照表1的配方和条件保存病毒。
表1保存病毒的不同配方的介质
照表1准备样品，放入37℃温箱，48小时后，将上述样品转入-80℃冰箱，直到做病毒滴度检测。其中样品G8在滴定前从-80℃冰箱中取出原始病毒，稀释后与其他七组样品同时做病毒滴定。G8的结果为判定其他组病毒样品稳定性的参考标准。
将Vero细胞按每孔8×105的细胞量接种到6孔板，每孔3ml，置37℃二氧化碳培养箱培养24h。将病毒样品按表2的方案进行梯度稀释。
表2病毒滴定稀释过程
将已经换好不含FBS培养基的六孔板分别从37度培养箱中取出，吸去培养基，每孔加入1ml的稀释液，每个样品做4个复孔(2个六孔板/样品)。每孔1ml病毒稀释液加入后，放入37度培养箱，病毒吸附60分钟，吸出病毒液体，再加入2ml/孔的MEM(无FBS)培养液与甲基纤维素(1.5％)，放入37度培养箱中培养96小时。
96小时后，弃覆盖物，每孔加1ml 4％戊二醛溶液，室温放置30min后弃液，再加入2％结晶紫染色液染色，1ml/孔，室温染色15min，用软化水轻冲洗，晾干。六孔板晾干后，由于病毒引起的死亡细胞不着色，形成白色斑点，在医用观片灯下计数空斑。
结果计算：取孔内空斑数20～150个的孔作为滴度计数，取平均数后乘病毒稀释度，如管6的孔中空斑平均数为20个，即病毒滴度为20×106，即为2.0*107PFU/ml。上述样品每个做三个重复。通过空斑的结果计算出病毒的滴度，G1-G7的结果与G8相比，从而判定病毒最稳定的保护剂。
测得各组病毒滴度的结果见图68。测试结果表明，在37℃以配方G5保存的病毒活性保持良好，与-80℃保存的病毒的活性基本无区别。虽然通常认为增加蔗糖可以提高病毒液的稳定性，但出乎意料的是，HSV-1溶瘤病毒在有蔗糖存在的情况下，无论是否有甘油存在，都不利于保持病毒活性。
实施例38蛋白在小鼠血清中的稳定性探索性研究
VG001-1-2携带人PD-L1阻断肽(TF)，PD-L1阻断肽的C-末端可包含Fc序列。Fc可来自IgG亚类之一，为了解TF末端融合不同来源的Fc序列所形成的各种融合蛋白的稳定性，进行以下实验。
细胞培养
293细胞用含双抗和10％胎牛血清的RPMI-1640培养液，在含有5％CO2的37℃培养箱中培养。细胞密度达到80％左右时用胰蛋白酶进行消化，以1：3-4比例进行传代培养。
质粒提取：对于VG001-1-2，在其PD-L1编码区域末端分别插入编码IgG1 Fc或IgG4Fc片段的序列，得到质粒VG001-1-2-Fc1和VG001-1-2-Fc4，二者分别能够表达融合IgG1 Fc的PD-L1、融合IgG4 Fc的PD-L1。将上述两个质粒用热激法分别转化大肠杆菌BL21，在LB+AMP的细菌培养板上过夜37℃培养，挑出单菌落，放入LB+AMP液体培养基(2-3ml)中37°摇床(150rpm/分)过夜培养。
从上述培养和浑浊的培养基中提取质粒，标记Fc-1和Fc-4，以及提取日期。
在琼脂糖电泳上，鉴定提取质粒的质量，同时用DNA浓度检测仪，检测质粒DNA的浓度。
2.3质粒转染
将293细胞铺在6孔板，放在细胞培养箱中过夜贴壁培养。
将上述两个质粒，根据质粒浓度，按照质粒转染的说明书的方法，混合质粒与质粒转染试剂以及无血清培养基。加入293细胞上，孵育4小时之后，换为6％FBS血清的培养基继续培养48小时。
质粒转染后，于48小时取上清(2ml)。
所有样品上清样品冻在-80℃冰箱。
2.4蛋白与血清的混合
取上述转染后的上清(2mL)和小鼠血清从-80℃取出，放在冰上融化后，按表3的配方制备样品。
表3：混合样品的配置
制备好样品后，样品组G01/G02转入-20℃冰箱保存，其余各组放入37℃温箱，样品组G1/G2在第14天转入-20C冰箱保存，样品组G3/G4在第28天转入-20℃冰箱保存。全部样品收集结束后待ELISA检测。
样品的ELISA检测
样品于冰上解冻。每个样品取出300ul，做ELISA检测，每个孔100ul，每个样品三个重复。按照试剂盒的说明，计算出每个样品中蛋白的含量。
1)用试剂盒中的抗体包被ELISA板，4℃过夜；
2)用试剂盒中的洗液把包被的ELISA板子洗两次，每次洗涤都用吸水纸吸干孔里的液体；
3)加入封闭液，室温封闭2小时；
4)用洗液洗涤两次后，加入配置好的标准曲线和上述样品以及Assay buffer，每个样品2个重复；
5)用封板膜防止孔中液体蒸发，室温放置2小时孵育；
6)孵育结束，用洗涤液洗涤四次，每次均用吸水纸晾干孔中液体；
7)按照试剂盒要求，加入100ul/孔的检测抗体，封板后，室温孵育1小时；
8)孵育结束，用洗涤液洗涤四次，每次均用吸水纸晾干孔中液体；
9)每孔加入100ul底物，室温避光孵育15分钟；
10)每孔再加入100ul终止液，室温孵育10-20分钟；
11)调试ELISA酶标仪，在450nm和570nm的波长下读板；
12)按照试剂盒的要求，分析数据。
根据ELISA结果，判定每个样品中的TF-Fc与ELISA试剂盒中IgG4或者IgG1抗体结合的能力，得出IgG1 Fc与IgG4 Fc融合蛋白在小鼠血清中的稳定性(图69)。
由测试结果可见，与传统的认为相反，TF与IgG1 Fc融合的结构在血清中不如与IgG4 Fc融合的结构稳定。在28天之后，TF-IgG4Fc融合蛋白与PD-L1结合的能力与TF-IgG1Fc融合蛋白相比明显更高，具有统计学显著差异(p＝0.01)。
以下为本文披露内容的其他示例性的实施方式：
1)一种HSV载体，其表达IL12、IL15和/或IL受体15α亚单位中的一种或多种。在一种实施方式中，该HSV载体包含表达IL12、IL15和该IL受体15α亚单位的表达盒。在各种实施方式中，被表达的IL12、IL15和IL15受体α亚单位序列是哺乳动物来源的(例如，鼠或人来源)。在优选的实施方式中，该表达盒表达鼠或人IL12、鼠或人IL15以及鼠或人IL15受体α亚单位。在另外的实施方式中，该表达盒表达鼠或人IL12、hIL15、以及鼠和h15受体α亚单位。
2)实施方式1的HSV载体，其中编码自剪切肽2A的核酸序列位于IL12、IL15和IL15受体α亚单位的编码序列之间的框内。在优选的实施方式中，IL12为鼠或人序列，IL15为人序列并且IL15受体α亚单位为人序列。
3)实施方式2的HSV载体，其中该核酸序列编码选自
VKQTLNFDLLKLAGDVESNPGP、QCTNYALLKLAGDVESNPGP、ATNF-SLLKQAGDVEENPGP、HYAGYFADLLIHDIETNPGP、GIFN-AHYAGYFADLLIHDIETNPGP、KAVRGYHADYYKQRLIHDVEMNPGP、GATNF-SLLKLAGDVELNPGP、EGRGSLLTCGDVEENPGP、AARQMLLLLSGDVETNPGP、FLRKRTQLLMSGDVESNPGP、GSWTDILLLLSGDVETNPGP、TRAEUEDELIRAGIESNPGP、AKFQIDKILISGDVELNPGP、SKFQIDKILISGDIELNPGP、SSIIRTKMLVSGDVEENPGP和CDAQRQKLLLSGDIEQNPGP的自剪切肽2A。
4)实施方式1至3的HSV载体，其中一个或多个IRES序列位于IL12、IL15和IL15受体α亚单位的编码序列之间。在优选的实施方式中，IL12是鼠或人序列，IL15是人序列，以及IL15受体α亚单位是人序列。
5)实施方式1至4的HSV载体，其中该IL15和IL15受体α亚单位利用IRES序列共表达。在优选的实施方式中，IL12是鼠或人序列，IL15是人序列，以及IL15受体α亚单位是人序列。
6)实施方式1至5中任一项的HSV载体，其中该IL15和IL15受体α亚单位通过双向启动子表达。在优选的实施方式中，IL12是鼠或人序列，IL15是人序列，以及IL15受体α亚单位是人序列。
7)实施方式6的HSV载体，其中该双向启动子是bi-CMV。
8)实施方式1至7中任一项的HSV载体，其中IL15和IL15受体α亚单位中的每一个在编码Lys5或Glu5的核酸序列之后。在优选的实施方式中，IL12是鼠或人序列、IL15是人序列、以及IL15受体α亚单位是人序列。
9)实施方式1至8中任一项的HSV载体，其中该hIL15受体α亚单位选自由变体1、变体2、变体3和变体4组成的组。
10)实施方式1至9中任一项的HSV载体，进一步包含一种或多种PD-L1阻断肽的表达盒，或者，其中所述表达盒包含一种或多种PD-L1阻断肽。
11)实施方式1至10中任一项的HSV载体，进一步包含编码多个PD-L1阻断肽之间的肽接头的序列。
12)实施方式1至11中任一项的HSV载体，在多个PD-L1阻断肽之间进一步包含一个或多个IRES序列。
13)实施方式1至12中任一项的HSV载体，进一步包含编码连接至所述PD-L1阻断肽的3’-端的Fc区的序列。
14)实施方式1至13中任一项的HSV载体，其中将表达盒插入到内部重复区或HSV基因组的末端重复区中。
15)实施方式10的HSV载体，其中将编码PD-L1阻断肽的序列插入到病毒基因之间，例如，UL3和UL4病毒基因之间、UL50和UL51基因之间、和/或US1和US2之间。
16)实施方式1至15中任一项的HSV载体，在ICP4或ICP27调控区中进一步包含NFkB和OCT4/SOX2增强元件。
17)实施方式1至16中任一项的HSV载体，其中ICP34.5基因缺失。
18)实施方式1至17中任一项的HSV载体，其中该表达盒包含至少一个双向CMV启动子。
19)实施方式1至18中任一项的HSV载体，其中该表达盒包含至少一个细胞启动子。
20)实施方式1至19中任一项的HSV载体，将该IL12/IL15/IL15受体α亚单位的表达盒插入到内部重复区或末端重复区中，其中原始病毒序列被所述表达盒替换。
21)实施方式1-20中任一项的HSV载体，其中该HSV为HSV-1或HSV-2。
22)实施方式1至21中任一项的HSV载体，其中通过包含在肿瘤细胞中低表达的miRNA的靶序列的3’UTR来调控该ICP34.5基因。
23)一种药物组合物，包含实施方式1至22中任一项的HSV载体，和可药用载体。
24)治疗癌症的方法，包括向患者施用实施方式1至22中任一项的HSV载体，或实施方式23的药物组合物。
25)根据实施方式24的方法，其中所述癌症选自由癌(carcinomas)、白血病、淋巴瘤、骨髓瘤和肉瘤组成的组。
本文所引用或提及的所有专利、出版物、科学文章、网站以及其他文件和材料均表示本发明所属领域技术人员的技能水平，并且每一篇所引用的文件和材料均以引用的方式并入本文中，就如同单独地或整体地以相同的程度将其以全部内容被结合于本文一样。申请人保留将任何此类专利、出版物、科学文章、网站、电子信息和其他参考资料或文件中的任何和所有材料和信息实际结合于本说明书的权利。
本专利的文字说明部分包括所有权利要求。此外，所有权利要求，包括所有原始权利要求以及任何和所有优先权文件中的所有权利要求，均以引用方式全部并入说明书的的书面说明部分，申请人保留实际并入书面说明或本申请、任意和所有这样的权利要求的任何其他部分的权利。因此，例如，在任何情况下，均不得将专利解释为声称没有就专利的书面描述部分的书面文件原文中没有规定权利要求的准确措辞的主张提供权利要求的书面描述。
根据法律对权利要求进行解释。然而，尽管声称或认为容易或难以解释任何权利要求或其部分，但在任何情况下，在该专利申请期间，任何权利要求或其任何部分的调整或修改均不得被解释为已丧失任何同等权利，其不构成现有技术的一部分。
本说明书中公开的所有特征可以任意组合。因此，除非另有明确说明，否则所公开的每个特征仅为等同或类似特征的一系列的示例。
应当理解，尽管已结合其详细描述对本发明进行了描述，但上述描述旨在说明而不是限制由所附权利要求的范围限定的本发明的范围。因此，从上述内容来看，尽管为了说明的目的，本文已经描述了本发明的具体非限制性实施方式，但是在不偏离本发明精神和范围的情况下可以进行各种修改。其他方面、优点和修改均包括在所附权利要求的范围内，并且本发明不限于所附的权利要求。
本文所述的具体方法和组合物代表优选的非限制性实施方式，并且是示例性的而并非意在作为对本发明范围的限制。本领域技术人员在阅读本说明书后，将产生其他目的、方面和实施方式，并且包含在权利要求范围所定义的发明精神中。对于本领域技术人员来说，很容易理解，在不偏离本发明的范围和精神的情况下可以对本文所公开的发明进行不同的替换和修改。本文中适当地说明性地描述的发明可以在没有任何元素或元素、或限制或限制的情况下实施，而这些元素或元素、或限制或限制在本文中不必具体披露。因此，例如，在本文的每一实例中，在本发明的非限制性实施例或实例中，术语“包含”、“包括”、“含有”等将被扩展地和不受限制地理解。本文适当地阐述的方法和方法可以不同的步骤顺序来实施，并且它们不一定限于本文或权利要求中所示的步骤顺序。
已使用的术语和表达式用作描述术语而非限制性术语，并且在使用这些术语和表达式时无意排除所示和描述的特征或其部分的任何等同物，但应认识到，在所要求的发明范围内可以进行各种修改。因此，应当理解，尽管本发明已通过各种非限制性实施方式和/或优选非限制性实施方式和可选特征具体公开，但本领域技术人员能够根据本发明所公开构思的任何和所有修改和变化被认为是在如所附权利要求书所限定的范围内。
本文对本发明进行了广泛和一般的描述。属于本发明公开内容的每个较窄的种和亚种也构成本发明的一部分。这包括对本发明的一般性描述，但有附带条件或负面限制，即从属中除去任何主题事项，无论此处是否具体地叙述了删去的材料。
还应理解，如本文和所附权利要求书中所用，除非上下文另有明确规定，单数形式“一个”、“一种”和“该”包括复数形式，术语“X和/或Y”表示“X”或“Y”或“X”和“Y”二者，并且名词后的字母“s”同时表示复数和那个名词的单数形式。此外，本发明中的特征或方面是以马库什组的形式描述的，并且本领域技术人员将认识到，本发明包含并且因此也以马库什组的任何个别成员和任何成员的任何亚组的形式描述，并且申请人保留修改申请或权利要求书的权利，尤其是针对马库什组的任何个别成员或任何成员的亚组。
其他非限制性实施方式包括在所附权利要求中。不得将本专利解释为仅限于本文具体地和/或明确地公开的具体实施例或非限制性实施例或方法。在任何情况下，均不得将专利解释为受到专利和商标局的任何审查员或任何其他官员或雇员所作的任何声明的限制，除非该声明是申请人在书面答复文件中明确采纳，且未做限制或保留的。
序列表
<110> 上海复诺健生物科技有限公司
<120> 表达免疫系统-刺激分子的溶瘤性单纯疱疹病毒载体
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<210> 1
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<212> PRT
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Met Cys Pro Gln Lys Leu Thr Ile Ser Trp Phe Ala Ile Val Leu Leu
1 5 10 15
Val Ser Pro Leu Met Ala Met Trp Glu Leu Glu Lys Asp Val Tyr Val
20 25 30
Val Glu Val Asp Trp Thr Pro Asp Ala Pro Gly Glu Thr Val Asn Leu
35 40 45
Thr Cys Asp Thr Pro Glu Glu Asp Asp Ile Thr Trp Thr Ser Asp Gln
50 55 60
Arg His Gly Val Ile Gly Ser Gly Lys Thr Leu Thr Ile Thr Val Lys
65 70 75 80
Glu Phe Leu Asp Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Thr
85 90 95
Leu Ser His Ser His Leu Leu Leu His Lys Lys Glu Asn Gly Ile Trp
100 105 110
Ser Thr Glu Ile Leu Lys Asn Phe Lys Asn Lys Thr Phe Leu Lys Cys
115 120 125
Glu Ala Pro Asn Tyr Ser Gly Arg Phe Thr Cys Ser Trp Leu Val Gln
130 135 140
Arg Asn Met Asp Leu Lys Phe Asn Ile Lys Ser Ser Ser Ser Ser Pro
145 150 155 160
Asp Ser Arg Ala Val Thr Cys Gly Met Ala Ser Leu Ser Ala Glu Lys
165 170 175
Val Thr Leu Asp Gln Arg Asp Tyr Glu Lys Tyr Ser Val Ser Cys Gln
180 185 190
Glu Asp Val Thr Cys Pro Thr Ala Glu Glu Thr Leu Pro Ile Glu Leu
195 200 205
Ala Leu Glu Ala Arg Gln Gln Asn Lys Tyr Glu Asn Tyr Ser Thr Ser
210 215 220
Phe Phe Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln
225 230 235 240
Met Lys Pro Leu Lys Asn Ser Gln Val Glu Val Ser Trp Glu Tyr Pro
245 250 255
Asp Ser Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Lys Phe Phe Val
260 265 270
Arg Ile Gln Arg Lys Lys Glu Lys Met Lys Glu Thr Glu Glu Gly Cys
275 280 285
Asn Gln Lys Gly Ala Phe Leu Val Glu Lys Thr Ser Thr Glu Val Gln
290 295 300
Cys Lys Gly Gly Asn Val Cys Val Gln Ala Gln Asp Arg Tyr Tyr Asn
305 310 315 320
Ser Ser Cys Ser Lys Trp Ala Cys Val Pro Cys Arg Val Arg Ser
325 330 335
<210> 2
<211> 162
<212> PRT
<213> 智人
<400> 2
Met Arg Ile Ser Lys Pro His Leu Arg Ser Ile Ser Ile Gln Cys Tyr
1 5 10 15
Leu Cys Leu Leu Leu Asn Ser His Phe Leu Thr Glu Ala Gly Ile His
20 25 30
Val Phe Ile Leu Gly Cys Phe Ser Ala Gly Leu Pro Lys Thr Glu Ala
35 40 45
Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile
50 55 60
Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His
65 70 75 80
Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln
85 90 95
Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu
100 105 110
Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val
115 120 125
Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile
130 135 140
Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn
145 150 155 160
Thr Ser
<210> 3
<211> 267
<212> PRT
<213> 智人
<400> 3
Met Ala Pro Arg Arg Ala Arg Gly Cys Arg Thr Leu Gly Leu Pro Ala
1 5 10 15
Leu Leu Leu Leu Leu Leu Leu Arg Pro Pro Ala Thr Arg Gly Ile Thr
20 25 30
Cys Pro Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val Lys Ser
35 40 45
Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly Phe Lys
50 55 60
Arg Lys Ala Gly Thr Ser Ser Leu Thr Glu Cys Val Leu Asn Lys Ala
65 70 75 80
Thr Asn Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys Ile Arg Asp
85 90 95
Pro Ala Leu Val His Gln Arg Pro Ala Pro Pro Ser Thr Val Thr Thr
100 105 110
Ala Gly Val Thr Pro Gln Pro Glu Ser Leu Ser Pro Ser Gly Lys Glu
115 120 125
Pro Ala Ala Ser Ser Pro Ser Ser Asn Asn Thr Ala Ala Thr Thr Ala
130 135 140
Ala Ile Val Pro Gly Ser Gln Leu Met Pro Ser Lys Ser Pro Ser Thr
145 150 155 160
Gly Thr Thr Glu Ile Ser Ser His Glu Ser Ser His Gly Thr Pro Ser
165 170 175
Gln Thr Thr Ala Lys Asn Trp Glu Leu Thr Ala Ser Ala Ser His Gln
180 185 190
Pro Pro Gly Val Tyr Pro Gln Gly His Ser Asp Thr Thr Val Ala Ile
195 200 205
Ser Thr Ser Thr Val Leu Leu Cys Gly Leu Ser Ala Val Ser Leu Leu
210 215 220
Ala Cys Tyr Leu Lys Ser Arg Gln Thr Pro Pro Leu Ala Ser Val Glu
225 230 235 240
Met Glu Ala Met Glu Ala Leu Pro Val Thr Trp Gly Thr Ser Ser Arg
245 250 255
Asp Glu Asp Leu Glu Asn Cys Ser His His Leu
260 265
<210> 4
<211> 234
<212> PRT
<213> 智人
<400> 4
Met Ala Pro Arg Arg Ala Arg Gly Cys Arg Thr Leu Gly Leu Pro Ala
1 5 10 15
Leu Leu Leu Leu Leu Leu Leu Arg Pro Pro Ala Thr Arg Gly Ile Thr
20 25 30
Cys Pro Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val Lys Ser
35 40 45
Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly Phe Lys
50 55 60
Arg Lys Ala Gly Thr Ser Ser Leu Thr Glu Cys Val Leu Asn Lys Ala
65 70 75 80
Thr Asn Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys Ile Lys Pro
85 90 95
Ala Ala Ser Ser Pro Ser Ser Asn Asn Thr Ala Ala Thr Thr Ala Ala
100 105 110
Ile Val Pro Gly Ser Gln Leu Met Pro Ser Lys Ser Pro Ser Thr Gly
115 120 125
Thr Thr Glu Ile Ser Ser His Glu Ser Ser His Gly Thr Pro Ser Gln
130 135 140
Thr Thr Ala Lys Asn Trp Glu Leu Thr Ala Ser Ala Ser His Gln Pro
145 150 155 160
Pro Gly Val Tyr Pro Gln Gly His Ser Asp Thr Thr Val Ala Ile Ser
165 170 175
Thr Ser Thr Val Leu Leu Cys Gly Leu Ser Ala Val Ser Leu Leu Ala
180 185 190
Cys Tyr Leu Lys Ser Arg Gln Thr Pro Pro Leu Ala Ser Val Glu Met
195 200 205
Glu Ala Met Glu Ala Leu Pro Val Thr Trp Gly Thr Ser Ser Arg Asp
210 215 220
Glu Asp Leu Glu Asn Cys Ser His His Leu
225 230
<210> 5
<211> 231
<212> PRT
<213> 智人
<400> 5
Met Ser Val Glu His Ala Asp Ile Trp Val Lys Ser Tyr Ser Leu Tyr
1 5 10 15
Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly Phe Lys Arg Lys Ala Gly
20 25 30
Thr Ser Ser Leu Thr Glu Cys Val Leu Asn Lys Ala Thr Asn Val Ala
35 40 45
His Trp Thr Thr Pro Ser Leu Lys Cys Ile Arg Asp Pro Ala Leu Val
50 55 60
His Gln Arg Pro Ala Pro Pro Ser Thr Val Thr Thr Ala Gly Val Thr
65 70 75 80
Pro Gln Pro Glu Ser Leu Ser Pro Ser Gly Lys Glu Pro Ala Ala Ser
85 90 95
Ser Pro Ser Ser Asn Asn Thr Ala Ala Thr Thr Ala Ala Ile Val Pro
100 105 110
Gly Ser Gln Leu Met Pro Ser Lys Ser Pro Ser Thr Gly Thr Thr Glu
115 120 125
Ile Ser Ser His Glu Ser Ser His Gly Thr Pro Ser Gln Thr Thr Ala
130 135 140
Lys Asn Trp Glu Leu Thr Ala Ser Ala Ser His Gln Pro Pro Gly Val
145 150 155 160
Tyr Pro Gln Gly His Ser Asp Thr Thr Val Ala Ile Ser Thr Ser Thr
165 170 175
Val Leu Leu Cys Gly Leu Ser Ala Val Ser Leu Leu Ala Cys Tyr Leu
180 185 190
Lys Ser Arg Gln Thr Pro Pro Leu Ala Ser Val Glu Met Glu Ala Met
195 200 205
Glu Ala Leu Pro Val Thr Trp Gly Thr Ser Ser Arg Asp Glu Asp Leu
210 215 220
Glu Asn Cys Ser His His Leu
225 230
<210> 6
<211> 353
<212> PRT
<213> 智人
<400> 6
Met Arg Leu Ala Gly Arg Gln Val Pro Glu Gln Arg Ser Pro Pro Pro
1 5 10 15
Pro Gly Leu Gly Ser Ala Arg Pro Gly Ser Pro Ala Val Ser Cys Gly
20 25 30
Ala Ala Ala Met Ala Pro Arg Arg Ala Arg Gly Cys Arg Thr Leu Gly
35 40 45
Leu Pro Ala Leu Leu Leu Leu Leu Leu Leu Arg Pro Pro Ala Thr Arg
50 55 60
Asp Ala Arg Asp Arg Leu Ala Val Leu Ala Gly Arg Ser Arg Ile Ser
65 70 75 80
Glu Ser Phe Asn His Glu Val Gln Thr His Glu Ala Cys Val Arg Leu
85 90 95
Arg Thr Met Glu Asn Cys Pro Gln Cys His His His Arg Thr Ser Arg
100 105 110
Gln Gln Ala Gly Ile Thr Cys Pro Pro Pro Met Ser Val Glu His Ala
115 120 125
Asp Ile Trp Val Lys Ser Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile
130 135 140
Cys Asn Ser Gly Phe Lys Arg Lys Ala Gly Thr Ser Ser Leu Thr Glu
145 150 155 160
Cys Val Leu Asn Lys Ala Thr Asn Val Ala His Trp Thr Thr Pro Ser
165 170 175
Leu Lys Cys Ile Arg Asp Pro Ala Leu Val His Gln Arg Pro Ala Pro
180 185 190
Pro Ser Thr Val Thr Thr Ala Gly Val Thr Pro Gln Pro Glu Ser Leu
195 200 205
Ser Pro Ser Gly Lys Glu Pro Ala Ala Ser Ser Pro Ser Ser Asn Asn
210 215 220
Thr Ala Ala Thr Thr Ala Ala Ile Val Pro Gly Ser Gln Leu Met Pro
225 230 235 240
Ser Lys Ser Pro Ser Thr Gly Thr Thr Glu Ile Ser Ser His Glu Ser
245 250 255
Ser His Gly Thr Pro Ser Gln Thr Thr Ala Lys Asn Trp Glu Leu Thr
260 265 270
Ala Ser Ala Ser His Gln Pro Pro Gly Val Tyr Pro Gln Gly His Ser
275 280 285
Asp Thr Thr Val Ala Ile Ser Thr Ser Thr Val Leu Leu Cys Gly Leu
290 295 300
Ser Ala Val Ser Leu Leu Ala Cys Tyr Leu Lys Ser Arg Gln Thr Pro
305 310 315 320
Pro Leu Ala Ser Val Glu Met Glu Ala Met Glu Ala Leu Pro Val Thr
325 330 335
Trp Gly Thr Ser Ser Arg Asp Glu Asp Leu Glu Asn Cys Ser His His
340 345 350
Leu
<210> 7
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<220>
<221> misc_feature
<223> 合成序列
<400> 7
Lys Val Ser Ala Leu Lys Glu
1 5
<210> 8
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 8
Glu Val Ser Ala Leu Glu Lys
1 5
<210> 9
<211> 35
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 9
Lys Val Ser Ala Leu Lys Glu Lys Val Ser Ala Leu Lys Glu Lys Val
1 5 10 15
Ser Ala Leu Lys Glu Lys Val Ser Ala Leu Lys Glu Lys Val Ser Ala
20 25 30
Leu Lys Glu
35
<210> 10
<211> 35
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 10
Glu Val Ser Ala Leu Glu Lys Glu Val Ser Ala Leu Glu Lys Glu Val
1 5 10 15
Ser Ala Leu Glu Lys Glu Val Ser Ala Leu Glu Lys Glu Val Ser Ala
20 25 30
Leu Glu Lys
35
<210> 11
<211> 96
<212> PRT
<213> 智人
<400> 11
Met Ala Pro Arg Arg Ala Arg Gly Cys Arg Thr Leu Gly Leu Pro Ala
1 5 10 15
Leu Leu Leu Leu Leu Leu Leu Arg Pro Pro Ala Thr Arg Gly Ile Thr
20 25 30
Cys Pro Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val Lys Ser
35 40 45
Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly Phe Lys
50 55 60
Arg Lys Ala Gly Thr Ser Ser Leu Thr Glu Cys Val Leu Asn Lys Ala
65 70 75 80
Thr Asn Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys Ile Arg Asp
85 90 95
<210> 12
<211> 146
<212> PRT
<213> 智人
<400> 12
Met Ala Pro Arg Arg Ala Arg Gly Cys Arg Thr Leu Gly Leu Pro Ala
1 5 10 15
Leu Leu Leu Leu Leu Leu Leu Arg Pro Pro Ala Thr Arg Gly Ile Thr
20 25 30
Cys Pro Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val Lys Ser
35 40 45
Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly Phe Lys
50 55 60
Arg Lys Ala Gly Thr Ser Ser Leu Thr Glu Cys Val Leu Asn Lys Ala
65 70 75 80
Thr Asn Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys Ile Arg Asp
85 90 95
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu
100 105 110
Val Ser Ala Leu Glu Lys Glu Val Ser Ala Leu Glu Lys Glu Val Ser
115 120 125
Ala Leu Glu Lys Glu Val Ser Ala Leu Glu Lys Glu Val Ser Ala Leu
130 135 140
Glu Lys
145
<210> 13
<211> 403
<212> PRT
<213> 智人
<400> 13
Met Arg Leu Ala Gly Arg Gln Val Pro Glu Gln Arg Ser Pro Pro Pro
1 5 10 15
Pro Gly Leu Gly Ser Ala Arg Pro Gly Ser Pro Ala Val Ser Cys Gly
20 25 30
Ala Ala Ala Met Ala Pro Arg Arg Ala Arg Gly Cys Arg Thr Leu Gly
35 40 45
Leu Pro Ala Leu Leu Leu Leu Leu Leu Leu Arg Pro Pro Ala Thr Arg
50 55 60
Asp Ala Arg Asp Arg Leu Ala Val Leu Ala Gly Arg Ser Arg Ile Ser
65 70 75 80
Glu Ser Phe Asn His Glu Val Gln Thr His Glu Ala Cys Val Arg Leu
85 90 95
Arg Thr Met Glu Asn Cys Pro Gln Cys His His His Arg Thr Ser Arg
100 105 110
Gln Gln Ala Gly Ile Thr Cys Pro Pro Pro Met Ser Val Glu His Ala
115 120 125
Asp Ile Trp Val Lys Ser Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile
130 135 140
Cys Asn Ser Gly Phe Lys Arg Lys Ala Gly Thr Ser Ser Leu Thr Glu
145 150 155 160
Cys Val Leu Asn Lys Ala Thr Asn Val Ala His Trp Thr Thr Pro Ser
165 170 175
Leu Lys Cys Ile Arg Asp Pro Ala Leu Val His Gln Arg Pro Ala Pro
180 185 190
Pro Ser Thr Val Thr Thr Ala Gly Val Thr Pro Gln Pro Glu Ser Leu
195 200 205
Ser Pro Ser Gly Lys Glu Pro Ala Ala Ser Ser Pro Ser Ser Asn Asn
210 215 220
Thr Ala Ala Thr Thr Ala Ala Ile Val Pro Gly Ser Gln Leu Met Pro
225 230 235 240
Ser Lys Ser Pro Ser Thr Gly Thr Thr Glu Ile Ser Ser His Glu Ser
245 250 255
Ser His Gly Thr Pro Ser Gln Thr Thr Ala Lys Asn Trp Glu Leu Thr
260 265 270
Ala Ser Ala Ser His Gln Pro Pro Gly Val Tyr Pro Gln Gly His Ser
275 280 285
Asp Thr Thr Val Ala Ile Ser Thr Ser Thr Val Leu Leu Cys Gly Leu
290 295 300
Ser Ala Val Ser Leu Leu Ala Cys Tyr Leu Lys Ser Arg Gln Thr Pro
305 310 315 320
Pro Leu Ala Ser Val Glu Met Glu Ala Met Glu Ala Leu Pro Val Thr
325 330 335
Trp Gly Thr Ser Ser Arg Asp Glu Asp Leu Glu Asn Cys Ser His His
340 345 350
Leu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
355 360 365
Glu Val Ser Ala Leu Glu Lys Glu Val Ser Ala Leu Glu Lys Glu Val
370 375 380
Ser Ala Leu Glu Lys Glu Val Ser Ala Leu Glu Lys Glu Val Ser Ala
385 390 395 400
Leu Glu Lys
<210> 14
<211> 317
<212> PRT
<213> 智人
<400> 14
Met Ala Pro Arg Arg Ala Arg Gly Cys Arg Thr Leu Gly Leu Pro Ala
1 5 10 15
Leu Leu Leu Leu Leu Leu Leu Arg Pro Pro Ala Thr Arg Gly Ile Thr
20 25 30
Cys Pro Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val Lys Ser
35 40 45
Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly Phe Lys
50 55 60
Arg Lys Ala Gly Thr Ser Ser Leu Thr Glu Cys Val Leu Asn Lys Ala
65 70 75 80
Thr Asn Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys Ile Arg Asp
85 90 95
Pro Ala Leu Val His Gln Arg Pro Ala Pro Pro Ser Thr Val Thr Thr
100 105 110
Ala Gly Val Thr Pro Gln Pro Glu Ser Leu Ser Pro Ser Gly Lys Glu
115 120 125
Pro Ala Ala Ser Ser Pro Ser Ser Asn Asn Thr Ala Ala Thr Thr Ala
130 135 140
Ala Ile Val Pro Gly Ser Gln Leu Met Pro Ser Lys Ser Pro Ser Thr
145 150 155 160
Gly Thr Thr Glu Ile Ser Ser His Glu Ser Ser His Gly Thr Pro Ser
165 170 175
Gln Thr Thr Ala Lys Asn Trp Glu Leu Thr Ala Ser Ala Ser His Gln
180 185 190
Pro Pro Gly Val Tyr Pro Gln Gly His Ser Asp Thr Thr Val Ala Ile
195 200 205
Ser Thr Ser Thr Val Leu Leu Cys Gly Leu Ser Ala Val Ser Leu Leu
210 215 220
Ala Cys Tyr Leu Lys Ser Arg Gln Thr Pro Pro Leu Ala Ser Val Glu
225 230 235 240
Met Glu Ala Met Glu Ala Leu Pro Val Thr Trp Gly Thr Ser Ser Arg
245 250 255
Asp Glu Asp Leu Glu Asn Cys Ser His His Leu Gly Gly Gly Gly Ser
260 265 270
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Ser Ala Leu Glu
275 280 285
Lys Glu Val Ser Ala Leu Glu Lys Glu Val Ser Ala Leu Glu Lys Glu
290 295 300
Val Ser Ala Leu Glu Lys Glu Val Ser Ala Leu Glu Lys
305 310 315
<210> 15
<211> 215
<212> PRT
<213> 智人
<400> 15
Met Arg Ile Ser Lys Pro His Leu Arg Ser Ile Ser Ile Gln Cys Tyr
1 5 10 15
Leu Cys Leu Leu Leu Asn Ser His Phe Leu Thr Glu Ala Gly Ile His
20 25 30
Val Phe Ile Leu Gly Cys Phe Ser Ala Gly Leu Pro Lys Thr Glu Ala
35 40 45
Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile
50 55 60
Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His
65 70 75 80
Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln
85 90 95
Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu
100 105 110
Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val
115 120 125
Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile
130 135 140
Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn
145 150 155 160
Thr Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
165 170 175
Ser Cys Gly Gly Lys Val Ser Ala Leu Lys Glu Lys Val Ser Ala Leu
180 185 190
Lys Glu Lys Val Ser Ala Leu Lys Glu Lys Val Ser Ala Leu Lys Glu
195 200 205
Lys Val Ser Ala Leu Lys Glu
210 215
<210> 16
<211> 14
<212> PRT
<213> 智人
<400> 16
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 17
<211> 10
<212> PRT
<213> 智人
<400> 17
Glu Tyr Arg Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 18
<211> 10
<212> PRT
<213> 智人
<400> 18
Tyr Tyr Arg Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 19
<211> 14
<212> PRT
<213> 小鼠
<400> 19
Thr Arg Tyr Pro Ser Pro Ser Pro Lys Pro Glu Gly Arg Phe
1 5 10
<210> 20
<211> 10
<212> PRT
<213> 智人
<400> 20
Trp Asn Arg Leu Ser Pro Ser Asn Gln Thr
1 5 10
<210> 21
<211> 14
<212> PRT
<213> 智人
<400> 21
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Ala
1 5 10
<210> 22
<211> 14
<212> PRT
<213> 智人
<400> 22
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Arg
1 5 10
<210> 23
<211> 14
<212> PRT
<213> 智人
<400> 23
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Asn
1 5 10
<210> 24
<211> 14
<212> PRT
<213> 智人
<400> 24
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Asp
1 5 10
<210> 25
<211> 14
<212> PRT
<213> 智人
<400> 25
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Cys
1 5 10
<210> 26
<211> 14
<212> PRT
<213> 智人
<400> 26
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Gln
1 5 10
<210> 27
<211> 14
<212> PRT
<213> 智人
<400> 27
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Glu
1 5 10
<210> 28
<211> 14
<212> PRT
<213> 智人
<400> 28
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Gly
1 5 10
<210> 29
<211> 14
<212> PRT
<213> 智人
<400> 29
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln His
1 5 10
<210> 30
<211> 14
<212> PRT
<213> 智人
<400> 30
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Ile
1 5 10
<210> 31
<211> 14
<212> PRT
<213> 智人
<400> 31
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Leu
1 5 10
<210> 32
<211> 14
<212> PRT
<213> 智人
<400> 32
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Lys
1 5 10
<210> 33
<211> 14
<212> PRT
<213> 智人
<400> 33
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Met
1 5 10
<210> 34
<211> 14
<212> PRT
<213> 智人
<400> 34
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 35
<211> 14
<212> PRT
<213> 智人
<400> 35
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Pro
1 5 10
<210> 36
<211> 14
<212> PRT
<213> 智人
<400> 36
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Ser
1 5 10
<210> 37
<211> 14
<212> PRT
<213> 智人
<400> 37
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Thr
1 5 10
<210> 38
<211> 14
<212> PRT
<213> 智人
<400> 38
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Trp
1 5 10
<210> 39
<211> 14
<212> PRT
<213> 智人
<400> 39
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Tyr
1 5 10
<210> 40
<211> 14
<212> PRT
<213> 智人
<400> 40
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Val
1 5 10
<210> 41
<211> 14
<212> PRT
<213> 智人
<400> 41
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Ala Phe
1 5 10
<210> 42
<211> 14
<212> PRT
<213> 智人
<400> 42
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Arg Phe
1 5 10
<210> 43
<211> 14
<212> PRT
<213> 智人
<400> 43
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Asn Phe
1 5 10
<210> 44
<211> 14
<212> PRT
<213> 智人
<400> 44
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Asp Phe
1 5 10
<210> 45
<211> 14
<212> PRT
<213> 智人
<400> 45
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Cys Phe
1 5 10
<210> 46
<211> 14
<212> PRT
<213> 智人
<400> 46
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 47
<211> 14
<212> PRT
<213> 智人
<400> 47
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Glu Phe
1 5 10
<210> 48
<211> 14
<212> PRT
<213> 智人
<400> 48
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gly Phe
1 5 10
<210> 49
<211> 14
<212> PRT
<213> 智人
<400> 49
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly His Phe
1 5 10
<210> 50
<211> 14
<212> PRT
<213> 智人
<400> 50
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Ile Phe
1 5 10
<210> 51
<211> 14
<212> PRT
<213> 智人
<400> 51
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Leu Phe
1 5 10
<210> 52
<211> 14
<212> PRT
<213> 智人
<400> 52
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Lys Phe
1 5 10
<210> 53
<211> 14
<212> PRT
<213> 智人
<400> 53
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Met Phe
1 5 10
<210> 54
<211> 14
<212> PRT
<213> 智人
<400> 54
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Phe Phe
1 5 10
<210> 55
<211> 14
<212> PRT
<213> 智人
<400> 55
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Pro Phe
1 5 10
<210> 56
<211> 14
<212> PRT
<213> 智人
<400> 56
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Ser Phe
1 5 10
<210> 57
<211> 14
<212> PRT
<213> 智人
<400> 57
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Thr Phe
1 5 10
<210> 58
<211> 14
<212> PRT
<213> 智人
<400> 58
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Trp Phe
1 5 10
<210> 59
<211> 14
<212> PRT
<213> 智人
<400> 59
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Tyr Phe
1 5 10
<210> 60
<211> 14
<212> PRT
<213> 智人
<400> 60
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Val Phe
1 5 10
<210> 61
<211> 14
<212> PRT
<213> 智人
<400> 61
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Ala Gln Phe
1 5 10
<210> 62
<211> 14
<212> PRT
<213> 智人
<400> 62
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Arg Gln Phe
1 5 10
<210> 63
<211> 14
<212> PRT
<213> 智人
<400> 63
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Asn Gln Phe
1 5 10
<210> 64
<211> 14
<212> PRT
<213> 智人
<400> 64
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Asp Gln Phe
1 5 10
<210> 65
<211> 14
<212> PRT
<213> 智人
<400> 65
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Cys Gln Phe
1 5 10
<210> 66
<211> 14
<212> PRT
<213> 智人
<400> 66
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gln Gln Phe
1 5 10
<210> 67
<211> 14
<212> PRT
<213> 智人
<400> 67
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Glu Gln Phe
1 5 10
<210> 68
<211> 14
<212> PRT
<213> 智人
<400> 68
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 69
<211> 14
<212> PRT
<213> 智人
<400> 69
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala His Gln Phe
1 5 10
<210> 70
<211> 14
<212> PRT
<213> 智人
<400> 70
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Ile Gln Phe
1 5 10
<210> 71
<211> 14
<212> PRT
<213> 智人
<400> 71
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Leu Gln Phe
1 5 10
<210> 72
<211> 14
<212> PRT
<213> 智人
<400> 72
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Lys Gln Phe
1 5 10
<210> 73
<211> 14
<212> PRT
<213> 智人
<400> 73
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Met Gln Phe
1 5 10
<210> 74
<211> 14
<212> PRT
<213> 智人
<400> 74
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Phe Gln Phe
1 5 10
<210> 75
<211> 14
<212> PRT
<213> 智人
<400> 75
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Pro Gln Phe
1 5 10
<210> 76
<211> 14
<212> PRT
<213> 智人
<400> 76
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Ser Gln Phe
1 5 10
<210> 77
<211> 14
<212> PRT
<213> 智人
<400> 77
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Thr Gln Phe
1 5 10
<210> 78
<211> 14
<212> PRT
<213> 智人
<400> 78
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Trp Gln Phe
1 5 10
<210> 79
<211> 14
<212> PRT
<213> 智人
<400> 79
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Tyr Gln Phe
1 5 10
<210> 80
<211> 14
<212> PRT
<213> 智人
<400> 80
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Val Gln Phe
1 5 10
<210> 81
<211> 14
<212> PRT
<213> 智人
<400> 81
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 82
<211> 14
<212> PRT
<213> 智人
<400> 82
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Arg Gly Gln Phe
1 5 10
<210> 83
<211> 14
<212> PRT
<213> 智人
<400> 83
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Asn Gly Gln Phe
1 5 10
<210> 84
<211> 14
<212> PRT
<213> 智人
<400> 84
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Asp Gly Gln Phe
1 5 10
<210> 85
<211> 14
<212> PRT
<213> 智人
<400> 85
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Cys Gly Gln Phe
1 5 10
<210> 86
<211> 14
<212> PRT
<213> 智人
<400> 86
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Gln Gly Gln Phe
1 5 10
<210> 87
<211> 14
<212> PRT
<213> 智人
<400> 87
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Glu Gly Gln Phe
1 5 10
<210> 88
<211> 14
<212> PRT
<213> 智人
<400> 88
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Gly Gly Gln Phe
1 5 10
<210> 89
<211> 14
<212> PRT
<213> 智人
<400> 89
Thr Ala His Pro Ser Pro Ser Pro Arg Ser His Gly Gln Phe
1 5 10
<210> 90
<211> 14
<212> PRT
<213> 智人
<400> 90
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ile Gly Gln Phe
1 5 10
<210> 91
<211> 14
<212> PRT
<213> 智人
<400> 91
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Leu Gly Gln Phe
1 5 10
<210> 92
<211> 14
<212> PRT
<213> 智人
<400> 92
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Lys Gly Gln Phe
1 5 10
<210> 93
<211> 14
<212> PRT
<213> 智人
<400> 93
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Met Gly Gln Phe
1 5 10
<210> 94
<211> 14
<212> PRT
<213> 智人
<400> 94
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Phe Gly Gln Phe
1 5 10
<210> 95
<211> 14
<212> PRT
<213> 智人
<400> 95
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Pro Gly Gln Phe
1 5 10
<210> 96
<211> 14
<212> PRT
<213> 智人
<400> 96
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ser Gly Gln Phe
1 5 10
<210> 97
<211> 14
<212> PRT
<213> 智人
<400> 97
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Thr Gly Gln Phe
1 5 10
<210> 98
<211> 14
<212> PRT
<213> 智人
<400> 98
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Trp Gly Gln Phe
1 5 10
<210> 99
<211> 14
<212> PRT
<213> 智人
<400> 99
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Tyr Gly Gln Phe
1 5 10
<210> 100
<211> 14
<212> PRT
<213> 智人
<400> 100
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Val Gly Gln Phe
1 5 10
<210> 101
<211> 14
<212> PRT
<213> 智人
<400> 101
Thr Ala His Pro Ser Pro Ser Pro Arg Ala Ala Gly Gln Phe
1 5 10
<210> 102
<211> 14
<212> PRT
<213> 智人
<400> 102
Thr Ala His Pro Ser Pro Ser Pro Arg Arg Ala Gly Gln Phe
1 5 10
<210> 103
<211> 14
<212> PRT
<213> 智人
<400> 103
Thr Ala His Pro Ser Pro Ser Pro Arg Asn Ala Gly Gln Phe
1 5 10
<210> 104
<211> 14
<212> PRT
<213> 智人
<400> 104
Thr Ala His Pro Ser Pro Ser Pro Arg Asp Ala Gly Gln Phe
1 5 10
<210> 105
<211> 14
<212> PRT
<213> 智人
<400> 105
Thr Ala His Pro Ser Pro Ser Pro Arg Cys Ala Gly Gln Phe
1 5 10
<210> 106
<211> 14
<212> PRT
<213> 智人
<400> 106
Thr Ala His Pro Ser Pro Ser Pro Arg Gln Ala Gly Gln Phe
1 5 10
<210> 107
<211> 14
<212> PRT
<213> 智人
<400> 107
Thr Ala His Pro Ser Pro Ser Pro Arg Glu Ala Gly Gln Phe
1 5 10
<210> 108
<211> 14
<212> PRT
<213> 智人
<400> 108
Thr Ala His Pro Ser Pro Ser Pro Arg Gly Ala Gly Gln Phe
1 5 10
<210> 109
<211> 14
<212> PRT
<213> 智人
<400> 109
Thr Ala His Pro Ser Pro Ser Pro Arg His Ala Gly Gln Phe
1 5 10
<210> 110
<211> 14
<212> PRT
<213> 智人
<400> 110
Thr Ala His Pro Ser Pro Ser Pro Arg Ile Ala Gly Gln Phe
1 5 10
<210> 111
<211> 14
<212> PRT
<213> 智人
<400> 111
Thr Ala His Pro Ser Pro Ser Pro Arg Leu Ala Gly Gln Phe
1 5 10
<210> 112
<211> 14
<212> PRT
<213> 智人
<400> 112
Thr Ala His Pro Ser Pro Ser Pro Arg Lys Ala Gly Gln Phe
1 5 10
<210> 113
<211> 14
<212> PRT
<213> 智人
<400> 113
Thr Ala His Pro Ser Pro Ser Pro Arg Met Ala Gly Gln Phe
1 5 10
<210> 114
<211> 14
<212> PRT
<213> 智人
<400> 114
Thr Ala His Pro Ser Pro Ser Pro Arg Phe Ala Gly Gln Phe
1 5 10
<210> 115
<211> 14
<212> PRT
<213> 智人
<400> 115
Thr Ala His Pro Ser Pro Ser Pro Arg Pro Ala Gly Gln Phe
1 5 10
<210> 116
<211> 14
<212> PRT
<213> 智人
<400> 116
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 117
<211> 14
<212> PRT
<213> 智人
<400> 117
Thr Ala His Pro Ser Pro Ser Pro Arg Thr Ala Gly Gln Phe
1 5 10
<210> 118
<211> 14
<212> PRT
<213> 智人
<400> 118
Thr Ala His Pro Ser Pro Ser Pro Arg Trp Ala Gly Gln Phe
1 5 10
<210> 119
<211> 14
<212> PRT
<213> 智人
<400> 119
Thr Ala His Pro Ser Pro Ser Pro Arg Tyr Ala Gly Gln Phe
1 5 10
<210> 120
<211> 14
<212> PRT
<213> 智人
<400> 120
Thr Ala His Pro Ser Pro Ser Pro Arg Val Ala Gly Gln Phe
1 5 10
<210> 121
<211> 14
<212> PRT
<213> 智人
<400> 121
Thr Ala His Pro Ser Pro Ser Pro Ala Ser Ala Gly Gln Phe
1 5 10
<210> 122
<211> 14
<212> PRT
<213> 智人
<400> 122
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 123
<211> 14
<212> PRT
<213> 智人
<400> 123
Thr Ala His Pro Ser Pro Ser Pro Asn Ser Ala Gly Gln Phe
1 5 10
<210> 124
<211> 14
<212> PRT
<213> 智人
<400> 124
Thr Ala His Pro Ser Pro Ser Pro Asp Ser Ala Gly Gln Phe
1 5 10
<210> 125
<211> 14
<212> PRT
<213> 智人
<400> 125
Thr Ala His Pro Ser Pro Ser Pro Cys Ser Ala Gly Gln Phe
1 5 10
<210> 126
<211> 14
<212> PRT
<213> 智人
<400> 126
Thr Ala His Pro Ser Pro Ser Pro Gln Ser Ala Gly Gln Phe
1 5 10
<210> 127
<211> 14
<212> PRT
<213> 智人
<400> 127
Thr Ala His Pro Ser Pro Ser Pro Glu Ser Ala Gly Gln Phe
1 5 10
<210> 128
<211> 14
<212> PRT
<213> 智人
<400> 128
Thr Ala His Pro Ser Pro Ser Pro Gly Ser Ala Gly Gln Phe
1 5 10
<210> 129
<211> 14
<212> PRT
<213> 智人
<400> 129
Thr Ala His Pro Ser Pro Ser Pro His Ser Ala Gly Gln Phe
1 5 10
<210> 130
<211> 14
<212> PRT
<213> 智人
<400> 130
Thr Ala His Pro Ser Pro Ser Pro Ile Ser Ala Gly Gln Phe
1 5 10
<210> 131
<211> 14
<212> PRT
<213> 智人
<400> 131
Thr Ala His Pro Ser Pro Ser Pro Leu Ser Ala Gly Gln Phe
1 5 10
<210> 132
<211> 14
<212> PRT
<213> 智人
<400> 132
Thr Ala His Pro Ser Pro Ser Pro Lys Ser Ala Gly Gln Phe
1 5 10
<210> 133
<211> 14
<212> PRT
<213> 智人
<400> 133
Thr Ala His Pro Ser Pro Ser Pro Met Ser Ala Gly Gln Phe
1 5 10
<210> 134
<211> 14
<212> PRT
<213> 智人
<400> 134
Thr Ala His Pro Ser Pro Ser Pro Phe Ser Ala Gly Gln Phe
1 5 10
<210> 135
<211> 14
<212> PRT
<213> 智人
<400> 135
Thr Ala His Pro Ser Pro Ser Pro Pro Ser Ala Gly Gln Phe
1 5 10
<210> 136
<211> 14
<212> PRT
<213> 智人
<400> 136
Thr Ala His Pro Ser Pro Ser Pro Ser Ser Ala Gly Gln Phe
1 5 10
<210> 137
<211> 14
<212> PRT
<213> 智人
<400> 137
Thr Ala His Pro Ser Pro Ser Pro Thr Ser Ala Gly Gln Phe
1 5 10
<210> 138
<211> 14
<212> PRT
<213> 智人
<400> 138
Thr Ala His Pro Ser Pro Ser Pro Trp Ser Ala Gly Gln Phe
1 5 10
<210> 139
<211> 14
<212> PRT
<213> 智人
<400> 139
Thr Ala His Pro Ser Pro Ser Pro Tyr Ser Ala Gly Gln Phe
1 5 10
<210> 140
<211> 14
<212> PRT
<213> 智人
<400> 140
Thr Ala His Pro Ser Pro Ser Pro Val Ser Ala Gly Gln Phe
1 5 10
<210> 141
<211> 14
<212> PRT
<213> 智人
<400> 141
Thr Ala His Pro Ser Pro Ser Ala Arg Ser Ala Gly Gln Phe
1 5 10
<210> 142
<211> 14
<212> PRT
<213> 智人
<400> 142
Thr Ala His Pro Ser Pro Ser Arg Arg Ser Ala Gly Gln Phe
1 5 10
<210> 143
<211> 14
<212> PRT
<213> 智人
<400> 143
Thr Ala His Pro Ser Pro Ser Asn Arg Ser Ala Gly Gln Phe
1 5 10
<210> 144
<211> 14
<212> PRT
<213> 智人
<400> 144
Thr Ala His Pro Ser Pro Ser Asp Arg Ser Ala Gly Gln Phe
1 5 10
<210> 145
<211> 14
<212> PRT
<213> 智人
<400> 145
Thr Ala His Pro Ser Pro Ser Cys Arg Ser Ala Gly Gln Phe
1 5 10
<210> 146
<211> 14
<212> PRT
<213> 智人
<400> 146
Thr Ala His Pro Ser Pro Ser Gln Arg Ser Ala Gly Gln Phe
1 5 10
<210> 147
<211> 14
<212> PRT
<213> 智人
<400> 147
Thr Ala His Pro Ser Pro Ser Glu Arg Ser Ala Gly Gln Phe
1 5 10
<210> 148
<211> 14
<212> PRT
<213> 智人
<400> 148
Thr Ala His Pro Ser Pro Ser Gly Arg Ser Ala Gly Gln Phe
1 5 10
<210> 149
<211> 14
<212> PRT
<213> 智人
<400> 149
Thr Ala His Pro Ser Pro Ser His Arg Ser Ala Gly Gln Phe
1 5 10
<210> 150
<211> 14
<212> PRT
<213> 智人
<400> 150
Thr Ala His Pro Ser Pro Ser Ile Arg Ser Ala Gly Gln Phe
1 5 10
<210> 151
<211> 14
<212> PRT
<213> 智人
<400> 151
Thr Ala His Pro Ser Pro Ser Leu Arg Ser Ala Gly Gln Phe
1 5 10
<210> 152
<211> 14
<212> PRT
<213> 智人
<400> 152
Thr Ala His Pro Ser Pro Ser Lys Arg Ser Ala Gly Gln Phe
1 5 10
<210> 153
<211> 14
<212> PRT
<213> 智人
<400> 153
Thr Ala His Pro Ser Pro Ser Met Arg Ser Ala Gly Gln Phe
1 5 10
<210> 154
<211> 14
<212> PRT
<213> 智人
<400> 154
Thr Ala His Pro Ser Pro Ser Phe Arg Ser Ala Gly Gln Phe
1 5 10
<210> 155
<211> 14
<212> PRT
<213> 智人
<400> 155
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 156
<211> 14
<212> PRT
<213> 智人
<400> 156
Thr Ala His Pro Ser Pro Ser Ser Arg Ser Ala Gly Gln Phe
1 5 10
<210> 157
<211> 14
<212> PRT
<213> 智人
<400> 157
Thr Ala His Pro Ser Pro Ser Thr Arg Ser Ala Gly Gln Phe
1 5 10
<210> 158
<211> 14
<212> PRT
<213> 智人
<400> 158
Thr Ala His Pro Ser Pro Ser Trp Arg Ser Ala Gly Gln Phe
1 5 10
<210> 159
<211> 14
<212> PRT
<213> 智人
<400> 159
Thr Ala His Pro Ser Pro Ser Tyr Arg Ser Ala Gly Gln Phe
1 5 10
<210> 160
<211> 14
<212> PRT
<213> 智人
<400> 160
Thr Ala His Pro Ser Pro Ser Val Arg Ser Ala Gly Gln Phe
1 5 10
<210> 161
<211> 14
<212> PRT
<213> 智人
<400> 161
Thr Ala His Pro Ser Pro Ala Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 162
<211> 14
<212> PRT
<213> 智人
<400> 162
Thr Ala His Pro Ser Pro Arg Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 163
<211> 14
<212> PRT
<213> 智人
<400> 163
Thr Ala His Pro Ser Pro Asn Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 164
<211> 14
<212> PRT
<213> 智人
<400> 164
Thr Ala His Pro Ser Pro Asp Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 165
<211> 14
<212> PRT
<213> 智人
<400> 165
Thr Ala His Pro Ser Pro Cys Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 166
<211> 14
<212> PRT
<213> 智人
<400> 166
Thr Ala His Pro Ser Pro Glu Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 167
<211> 14
<212> PRT
<213> 智人
<400> 167
Thr Ala His Pro Ser Pro Gln Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 168
<211> 14
<212> PRT
<213> 智人
<400> 168
Thr Ala His Pro Ser Pro Gly Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 169
<211> 14
<212> PRT
<213> 智人
<400> 169
Thr Ala His Pro Ser Pro His Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 170
<211> 14
<212> PRT
<213> 智人
<400> 170
Thr Ala His Pro Ser Pro Ile Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 171
<211> 14
<212> PRT
<213> 智人
<400> 171
Thr Ala His Pro Ser Pro Leu Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 172
<211> 14
<212> PRT
<213> 智人
<400> 172
Thr Ala His Pro Ser Pro Lys Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 173
<211> 14
<212> PRT
<213> 智人
<400> 173
Thr Ala His Pro Ser Pro Met Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 174
<211> 14
<212> PRT
<213> 智人
<400> 174
Thr Ala His Pro Ser Pro Phe Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 175
<211> 14
<212> PRT
<213> 智人
<400> 175
Thr Ala His Pro Ser Pro Pro Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 176
<211> 14
<212> PRT
<213> 智人
<400> 176
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 177
<211> 14
<212> PRT
<213> 智人
<400> 177
Thr Ala His Pro Ser Pro Thr Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 178
<211> 14
<212> PRT
<213> 智人
<400> 178
Thr Ala His Pro Ser Pro Trp Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 179
<211> 14
<212> PRT
<213> 智人
<400> 179
Thr Ala His Pro Ser Pro Tyr Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 180
<211> 14
<212> PRT
<213> 智人
<400> 180
Thr Ala His Pro Ser Pro Val Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 181
<211> 14
<212> PRT
<213> 智人
<400> 181
Thr Ala His Pro Ser Ala Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 182
<211> 14
<212> PRT
<213> 智人
<400> 182
Thr Ala His Pro Ser Arg Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 183
<211> 14
<212> PRT
<213> 智人
<400> 183
Thr Ala His Pro Ser Asn Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 184
<211> 14
<212> PRT
<213> 智人
<400> 184
Thr Ala His Pro Ser Asp Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 185
<211> 14
<212> PRT
<213> 智人
<400> 185
Thr Ala His Pro Ser Cys Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 186
<211> 14
<212> PRT
<213> 智人
<400> 186
Thr Ala His Pro Ser Gln Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 187
<211> 14
<212> PRT
<213> 智人
<400> 187
Thr Ala His Pro Ser Glu Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 188
<211> 14
<212> PRT
<213> 智人
<400> 188
Thr Ala His Pro Ser Gly Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 189
<211> 14
<212> PRT
<213> 智人
<400> 189
Thr Ala His Pro Ser His Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 190
<211> 14
<212> PRT
<213> 智人
<400> 190
Thr Ala His Pro Ser Ile Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 191
<211> 14
<212> PRT
<213> 智人
<400> 191
Thr Ala His Pro Ser Leu Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 192
<211> 14
<212> PRT
<213> 智人
<400> 192
Thr Ala His Pro Ser Lys Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 193
<211> 14
<212> PRT
<213> 智人
<400> 193
Thr Ala His Pro Ser Met Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 194
<211> 14
<212> PRT
<213> 智人
<400> 194
Thr Ala His Pro Ser Phe Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 195
<211> 14
<212> PRT
<213> 智人
<400> 195
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 196
<211> 14
<212> PRT
<213> 智人
<400> 196
Thr Ala His Pro Ser Ser Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 197
<211> 14
<212> PRT
<213> 智人
<400> 197
Thr Ala His Pro Ser Thr Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 198
<211> 14
<212> PRT
<213> 智人
<400> 198
Thr Ala His Pro Ser Trp Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 199
<211> 14
<212> PRT
<213> 智人
<400> 199
Thr Ala His Pro Ser Tyr Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 200
<211> 14
<212> PRT
<213> 智人
<400> 200
Thr Ala His Pro Ser Val Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 201
<211> 14
<212> PRT
<213> 智人
<400> 201
Thr Ala His Pro Ala Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 202
<211> 14
<212> PRT
<213> 智人
<400> 202
Thr Ala His Pro Arg Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 203
<211> 14
<212> PRT
<213> 智人
<400> 203
Thr Ala His Pro Asn Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 204
<211> 14
<212> PRT
<213> 智人
<400> 204
Thr Ala His Pro Asp Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 205
<211> 14
<212> PRT
<213> 智人
<400> 205
Thr Ala His Pro Cys Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 206
<211> 14
<212> PRT
<213> 智人
<400> 206
Thr Ala His Pro Gln Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 207
<211> 14
<212> PRT
<213> 智人
<400> 207
Thr Ala His Pro Glu Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 208
<211> 14
<212> PRT
<213> 智人
<400> 208
Thr Ala His Pro Gly Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 209
<211> 14
<212> PRT
<213> 智人
<400> 209
Thr Ala His Pro His Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 210
<211> 14
<212> PRT
<213> 智人
<400> 210
Thr Ala His Pro Ile Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 211
<211> 14
<212> PRT
<213> 智人
<400> 211
Thr Ala His Pro Leu Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 212
<211> 14
<212> PRT
<213> 智人
<400> 212
Thr Ala His Pro Lys Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 213
<211> 14
<212> PRT
<213> 智人
<400> 213
Thr Ala His Pro Met Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 214
<211> 14
<212> PRT
<213> 智人
<400> 214
Thr Ala His Pro Phe Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 215
<211> 14
<212> PRT
<213> 智人
<400> 215
Thr Ala His Pro Pro Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 216
<211> 14
<212> PRT
<213> 智人
<400> 216
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 217
<211> 14
<212> PRT
<213> 智人
<400> 217
Thr Ala His Pro Thr Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 218
<211> 14
<212> PRT
<213> 智人
<400> 218
Thr Ala His Pro Trp Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 219
<211> 14
<212> PRT
<213> 智人
<400> 219
Thr Ala His Pro Tyr Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 220
<211> 14
<212> PRT
<213> 智人
<400> 220
Thr Ala His Pro Val Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 221
<211> 14
<212> PRT
<213> 智人
<400> 221
Thr Ala His Ala Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 222
<211> 14
<212> PRT
<213> 智人
<400> 222
Thr Ala His Arg Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 223
<211> 14
<212> PRT
<213> 智人
<400> 223
Thr Ala His Asn Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 224
<211> 14
<212> PRT
<213> 智人
<400> 224
Thr Ala His Asp Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 225
<211> 14
<212> PRT
<213> 智人
<400> 225
Thr Ala His Cys Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 226
<211> 14
<212> PRT
<213> 智人
<400> 226
Thr Ala His Gln Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 227
<211> 14
<212> PRT
<213> 智人
<400> 227
Thr Ala His Glu Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 228
<211> 14
<212> PRT
<213> 智人
<400> 228
Thr Ala His Gly Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 229
<211> 14
<212> PRT
<213> 智人
<400> 229
Thr Ala His His Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 230
<211> 14
<212> PRT
<213> 智人
<400> 230
Thr Ala His Ile Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 231
<211> 14
<212> PRT
<213> 智人
<400> 231
Thr Ala His Leu Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 232
<211> 14
<212> PRT
<213> 智人
<400> 232
Thr Ala His Lys Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 233
<211> 14
<212> PRT
<213> 智人
<400> 233
Thr Ala His Met Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 234
<211> 14
<212> PRT
<213> 智人
<400> 234
Thr Ala His Phe Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 235
<211> 14
<212> PRT
<213> 智人
<400> 235
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 236
<211> 14
<212> PRT
<213> 智人
<400> 236
Thr Ala His Ser Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 237
<211> 14
<212> PRT
<213> 智人
<400> 237
Thr Ala His Thr Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 238
<211> 14
<212> PRT
<213> 智人
<400> 238
Thr Ala His Trp Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 239
<211> 14
<212> PRT
<213> 智人
<400> 239
Thr Ala His Tyr Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 240
<211> 14
<212> PRT
<213> 智人
<400> 240
Thr Ala His Val Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 241
<211> 14
<212> PRT
<213> 智人
<400> 241
Thr Ala Ala Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 242
<211> 14
<212> PRT
<213> 智人
<400> 242
Thr Ala Arg Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 243
<211> 14
<212> PRT
<213> 智人
<400> 243
Thr Ala Asn Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 244
<211> 14
<212> PRT
<213> 智人
<400> 244
Thr Ala Asp Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 245
<211> 14
<212> PRT
<213> 智人
<400> 245
Thr Ala Cys Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 246
<211> 14
<212> PRT
<213> 智人
<400> 246
Thr Ala Gln Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 247
<211> 14
<212> PRT
<213> 智人
<400> 247
Thr Ala Glu Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 248
<211> 14
<212> PRT
<213> 智人
<400> 248
Thr Ala Gly Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 249
<211> 14
<212> PRT
<213> 智人
<400> 249
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 250
<211> 14
<212> PRT
<213> 智人
<400> 250
Thr Ala Ile Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 251
<211> 14
<212> PRT
<213> 智人
<400> 251
Thr Ala Leu Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 252
<211> 14
<212> PRT
<213> 智人
<400> 252
Thr Ala Lys Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 253
<211> 14
<212> PRT
<213> 智人
<400> 253
Thr Ala Met Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 254
<211> 14
<212> PRT
<213> 智人
<400> 254
Thr Ala Phe Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 255
<211> 14
<212> PRT
<213> 智人
<400> 255
Thr Ala Pro Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 256
<211> 14
<212> PRT
<213> 智人
<400> 256
Thr Ala Ser Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 257
<211> 14
<212> PRT
<213> 智人
<400> 257
Thr Ala Thr Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 258
<211> 14
<212> PRT
<213> 智人
<400> 258
Thr Ala Trp Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 259
<211> 14
<212> PRT
<213> 智人
<400> 259
Thr Ala Tyr Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 260
<211> 14
<212> PRT
<213> 智人
<400> 260
Thr Ala Val Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 261
<211> 14
<212> PRT
<213> 智人
<400> 261
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 262
<211> 14
<212> PRT
<213> 智人
<400> 262
Thr Arg His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 263
<211> 14
<212> PRT
<213> 智人
<400> 263
Thr Asn His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 264
<211> 14
<212> PRT
<213> 智人
<400> 264
Thr Asp His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 265
<211> 14
<212> PRT
<213> 智人
<400> 265
Thr Cys His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 266
<211> 14
<212> PRT
<213> 智人
<400> 266
Thr Gln His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 267
<211> 14
<212> PRT
<213> 智人
<400> 267
Thr Glu His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 268
<211> 14
<212> PRT
<213> 智人
<400> 268
Thr Gly His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 269
<211> 14
<212> PRT
<213> 智人
<400> 269
Thr His His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 270
<211> 14
<212> PRT
<213> 智人
<400> 270
Thr Ile His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 271
<211> 14
<212> PRT
<213> 智人
<400> 271
Thr Leu His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 272
<211> 14
<212> PRT
<213> 智人
<400> 272
Thr Lys His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 273
<211> 14
<212> PRT
<213> 智人
<400> 273
Thr Met His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 274
<211> 14
<212> PRT
<213> 智人
<400> 274
Thr Phe His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 275
<211> 14
<212> PRT
<213> 智人
<400> 275
Thr Pro His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 276
<211> 14
<212> PRT
<213> 智人
<400> 276
Thr Ser His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 277
<211> 14
<212> PRT
<213> 智人
<400> 277
Thr Thr His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 278
<211> 14
<212> PRT
<213> 智人
<400> 278
Thr Trp His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 279
<211> 14
<212> PRT
<213> 智人
<400> 279
Thr Tyr His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 280
<211> 14
<212> PRT
<213> 智人
<400> 280
Thr Val His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 281
<211> 14
<212> PRT
<213> 智人
<400> 281
Ala Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 282
<211> 14
<212> PRT
<213> 智人
<400> 282
Arg Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 283
<211> 14
<212> PRT
<213> 智人
<400> 283
Asn Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 284
<211> 14
<212> PRT
<213> 智人
<400> 284
Asp Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 285
<211> 14
<212> PRT
<213> 智人
<400> 285
Cys Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 286
<211> 14
<212> PRT
<213> 智人
<400> 286
Gln Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 287
<211> 14
<212> PRT
<213> 智人
<400> 287
Glu Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 288
<211> 14
<212> PRT
<213> 智人
<400> 288
Gly Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 289
<211> 14
<212> PRT
<213> 智人
<400> 289
His Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 290
<211> 14
<212> PRT
<213> 智人
<400> 290
Ile Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 291
<211> 14
<212> PRT
<213> 智人
<400> 291
Leu Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 292
<211> 14
<212> PRT
<213> 智人
<400> 292
Lys Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 293
<211> 14
<212> PRT
<213> 智人
<400> 293
Met Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 294
<211> 14
<212> PRT
<213> 智人
<400> 294
Phe Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 295
<211> 14
<212> PRT
<213> 智人
<400> 295
Pro Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 296
<211> 14
<212> PRT
<213> 智人
<400> 296
Ser Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 297
<211> 14
<212> PRT
<213> 智人
<400> 297
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 298
<211> 14
<212> PRT
<213> 智人
<400> 298
Trp Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 299
<211> 14
<212> PRT
<213> 智人
<400> 299
Tyr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 300
<211> 14
<212> PRT
<213> 智人
<400> 300
Val Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 301
<211> 10
<212> PRT
<213> 智人
<400> 301
Trp Tyr Arg Met Ser Pro Ser Asn Gln Ala
1 5 10
<210> 302
<211> 10
<212> PRT
<213> 智人
<400> 302
Trp Tyr Arg Met Ser Pro Ser Asn Gln Arg
1 5 10
<210> 303
<211> 10
<212> PRT
<213> 智人
<400> 303
Trp Tyr Arg Met Ser Pro Ser Asn Gln Asn
1 5 10
<210> 304
<211> 10
<212> PRT
<213> 智人
<400> 304
Trp Tyr Arg Met Ser Pro Ser Asn Gln Asp
1 5 10
<210> 305
<211> 10
<212> PRT
<213> 智人
<400> 305
Trp Tyr Arg Met Ser Pro Ser Asn Gln Cys
1 5 10
<210> 306
<211> 10
<212> PRT
<213> 智人
<400> 306
Trp Tyr Arg Met Ser Pro Ser Asn Gln Gln
1 5 10
<210> 307
<211> 10
<212> PRT
<213> 智人
<400> 307
Trp Tyr Arg Met Ser Pro Ser Asn Gln Glu
1 5 10
<210> 308
<211> 10
<212> PRT
<213> 智人
<400> 308
Trp Tyr Arg Met Ser Pro Ser Asn Gln Gly
1 5 10
<210> 309
<211> 10
<212> PRT
<213> 智人
<400> 309
Trp Tyr Arg Met Ser Pro Ser Asn Gln His
1 5 10
<210> 310
<211> 10
<212> PRT
<213> 智人
<400> 310
Trp Tyr Arg Met Ser Pro Ser Asn Gln Ile
1 5 10
<210> 311
<211> 10
<212> PRT
<213> 智人
<400> 311
Trp Tyr Arg Met Ser Pro Ser Asn Gln Leu
1 5 10
<210> 312
<211> 10
<212> PRT
<213> 智人
<400> 312
Trp Tyr Arg Met Ser Pro Ser Asn Gln Lys
1 5 10
<210> 313
<211> 10
<212> PRT
<213> 智人
<400> 313
Trp Tyr Arg Met Ser Pro Ser Asn Gln Met
1 5 10
<210> 314
<211> 10
<212> PRT
<213> 智人
<400> 314
Trp Tyr Arg Met Ser Pro Ser Asn Gln Phe
1 5 10
<210> 315
<211> 10
<212> PRT
<213> 智人
<400> 315
Trp Tyr Arg Met Ser Pro Ser Asn Gln Pro
1 5 10
<210> 316
<211> 10
<212> PRT
<213> 智人
<400> 316
Trp Tyr Arg Met Ser Pro Ser Asn Gln Ser
1 5 10
<210> 317
<211> 10
<212> PRT
<213> 智人
<400> 317
Trp Tyr Arg Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 318
<211> 10
<212> PRT
<213> 智人
<400> 318
Trp Tyr Arg Met Ser Pro Ser Asn Gln Trp
1 5 10
<210> 319
<211> 10
<212> PRT
<213> 智人
<400> 319
Trp Tyr Arg Met Ser Pro Ser Asn Gln Tyr
1 5 10
<210> 320
<211> 10
<212> PRT
<213> 智人
<400> 320
Trp Tyr Arg Met Ser Pro Ser Asn Gln Val
1 5 10
<210> 321
<211> 10
<212> PRT
<213> 智人
<400> 321
Trp Tyr Arg Met Ser Pro Ser Asn Ala Thr
1 5 10
<210> 322
<211> 10
<212> PRT
<213> 智人
<400> 322
Trp Tyr Arg Met Ser Pro Ser Asn Arg Thr
1 5 10
<210> 323
<211> 10
<212> PRT
<213> 智人
<400> 323
Trp Tyr Arg Met Ser Pro Ser Asn Asn Thr
1 5 10
<210> 324
<211> 10
<212> PRT
<213> 智人
<400> 324
Trp Tyr Arg Met Ser Pro Ser Asn Asp Thr
1 5 10
<210> 325
<211> 10
<212> PRT
<213> 智人
<400> 325
Trp Tyr Arg Met Ser Pro Ser Asn Cys Thr
1 5 10
<210> 326
<211> 10
<212> PRT
<213> 智人
<400> 326
Trp Tyr Arg Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 327
<211> 10
<212> PRT
<213> 智人
<400> 327
Trp Tyr Arg Met Ser Pro Ser Asn Glu Thr
1 5 10
<210> 328
<211> 10
<212> PRT
<213> 智人
<400> 328
Trp Tyr Arg Met Ser Pro Ser Asn Gly Thr
1 5 10
<210> 329
<211> 10
<212> PRT
<213> 智人
<400> 329
Trp Tyr Arg Met Ser Pro Ser Asn His Thr
1 5 10
<210> 330
<211> 10
<212> PRT
<213> 智人
<400> 330
Trp Tyr Arg Met Ser Pro Ser Asn Ile Thr
1 5 10
<210> 331
<211> 10
<212> PRT
<213> 智人
<400> 331
Trp Tyr Arg Met Ser Pro Ser Asn Leu Thr
1 5 10
<210> 332
<211> 10
<212> PRT
<213> 智人
<400> 332
Trp Tyr Arg Met Ser Pro Ser Asn Lys Thr
1 5 10
<210> 333
<211> 10
<212> PRT
<213> 智人
<400> 333
Trp Tyr Arg Met Ser Pro Ser Asn Met Thr
1 5 10
<210> 334
<211> 10
<212> PRT
<213> 智人
<400> 334
Trp Tyr Arg Met Ser Pro Ser Asn Phe Thr
1 5 10
<210> 335
<211> 10
<212> PRT
<213> 智人
<400> 335
Trp Tyr Arg Met Ser Pro Ser Asn Pro Thr
1 5 10
<210> 336
<211> 10
<212> PRT
<213> 智人
<400> 336
Trp Tyr Arg Met Ser Pro Ser Asn Ser Thr
1 5 10
<210> 337
<211> 10
<212> PRT
<213> 智人
<400> 337
Trp Tyr Arg Met Ser Pro Ser Asn Thr Thr
1 5 10
<210> 338
<211> 10
<212> PRT
<213> 智人
<400> 338
Trp Tyr Arg Met Ser Pro Ser Asn Trp Thr
1 5 10
<210> 339
<211> 10
<212> PRT
<213> 智人
<400> 339
Trp Tyr Arg Met Ser Pro Ser Asn Tyr Thr
1 5 10
<210> 340
<211> 10
<212> PRT
<213> 智人
<400> 340
Trp Tyr Arg Met Ser Pro Ser Asn Val Thr
1 5 10
<210> 341
<211> 10
<212> PRT
<213> 智人
<400> 341
Trp Tyr Arg Met Ser Pro Ser Ala Gln Thr
1 5 10
<210> 342
<211> 10
<212> PRT
<213> 智人
<400> 342
Trp Tyr Arg Met Ser Pro Ser Arg Gln Thr
1 5 10
<210> 343
<211> 10
<212> PRT
<213> 智人
<400> 343
Trp Tyr Arg Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 344
<211> 10
<212> PRT
<213> 智人
<400> 344
Trp Tyr Arg Met Ser Pro Ser Asp Gln Thr
1 5 10
<210> 345
<211> 10
<212> PRT
<213> 智人
<400> 345
Trp Tyr Arg Met Ser Pro Ser Cys Gln Thr
1 5 10
<210> 346
<211> 10
<212> PRT
<213> 智人
<400> 346
Trp Tyr Arg Met Ser Pro Ser Gln Gln Thr
1 5 10
<210> 347
<211> 10
<212> PRT
<213> 智人
<400> 347
Trp Tyr Arg Met Ser Pro Ser Glu Gln Thr
1 5 10
<210> 348
<211> 10
<212> PRT
<213> 智人
<400> 348
Trp Tyr Arg Met Ser Pro Ser Gly Gln Thr
1 5 10
<210> 349
<211> 10
<212> PRT
<213> 智人
<400> 349
Trp Tyr Arg Met Ser Pro Ser His Gln Thr
1 5 10
<210> 350
<211> 10
<212> PRT
<213> 智人
<400> 350
Trp Tyr Arg Met Ser Pro Ser Ile Gln Thr
1 5 10
<210> 351
<211> 10
<212> PRT
<213> 智人
<400> 351
Trp Tyr Arg Met Ser Pro Ser Leu Gln Thr
1 5 10
<210> 352
<211> 10
<212> PRT
<213> 智人
<400> 352
Trp Tyr Arg Met Ser Pro Ser Lys Gln Thr
1 5 10
<210> 353
<211> 10
<212> PRT
<213> 智人
<400> 353
Trp Tyr Arg Met Ser Pro Ser Met Gln Thr
1 5 10
<210> 354
<211> 10
<212> PRT
<213> 智人
<400> 354
Trp Tyr Arg Met Ser Pro Ser Phe Gln Thr
1 5 10
<210> 355
<211> 10
<212> PRT
<213> 智人
<400> 355
Trp Tyr Arg Met Ser Pro Ser Pro Gln Thr
1 5 10
<210> 356
<211> 10
<212> PRT
<213> 智人
<400> 356
Trp Tyr Arg Met Ser Pro Ser Ser Gln Thr
1 5 10
<210> 357
<211> 10
<212> PRT
<213> 智人
<400> 357
Trp Tyr Arg Met Ser Pro Ser Thr Gln Thr
1 5 10
<210> 358
<211> 10
<212> PRT
<213> 智人
<400> 358
Trp Tyr Arg Met Ser Pro Ser Trp Gln Thr
1 5 10
<210> 359
<211> 10
<212> PRT
<213> 智人
<400> 359
Trp Tyr Arg Met Ser Pro Ser Tyr Gln Thr
1 5 10
<210> 360
<211> 10
<212> PRT
<213> 智人
<400> 360
Trp Tyr Arg Met Ser Pro Ser Val Gln Thr
1 5 10
<210> 361
<211> 10
<212> PRT
<213> 智人
<400> 361
Trp Tyr Arg Met Ser Pro Ala Asn Gln Thr
1 5 10
<210> 362
<211> 10
<212> PRT
<213> 智人
<400> 362
Trp Tyr Arg Met Ser Pro Arg Asn Gln Thr
1 5 10
<210> 363
<211> 10
<212> PRT
<213> 智人
<400> 363
Trp Tyr Arg Met Ser Pro Asn Asn Gln Thr
1 5 10
<210> 364
<211> 10
<212> PRT
<213> 智人
<400> 364
Trp Tyr Arg Met Ser Pro Asp Asn Gln Thr
1 5 10
<210> 365
<211> 10
<212> PRT
<213> 智人
<400> 365
Trp Tyr Arg Met Ser Pro Cys Asn Gln Thr
1 5 10
<210> 366
<211> 10
<212> PRT
<213> 智人
<400> 366
Trp Tyr Arg Met Ser Pro Gln Asn Gln Thr
1 5 10
<210> 367
<211> 10
<212> PRT
<213> 智人
<400> 367
Trp Tyr Arg Met Ser Pro Glu Asn Gln Thr
1 5 10
<210> 368
<211> 10
<212> PRT
<213> 智人
<400> 368
Trp Tyr Arg Met Ser Pro Gly Asn Gln Thr
1 5 10
<210> 369
<211> 10
<212> PRT
<213> 智人
<400> 369
Trp Tyr Arg Met Ser Pro His Asn Gln Thr
1 5 10
<210> 370
<211> 10
<212> PRT
<213> 智人
<400> 370
Trp Tyr Arg Met Ser Pro Ile Asn Gln Thr
1 5 10
<210> 371
<211> 10
<212> PRT
<213> 智人
<400> 371
Trp Tyr Arg Met Ser Pro Leu Asn Gln Thr
1 5 10
<210> 372
<211> 10
<212> PRT
<213> 智人
<400> 372
Trp Tyr Arg Met Ser Pro Lys Asn Gln Thr
1 5 10
<210> 373
<211> 10
<212> PRT
<213> 智人
<400> 373
Trp Tyr Arg Met Ser Pro Met Asn Gln Thr
1 5 10
<210> 374
<211> 10
<212> PRT
<213> 智人
<400> 374
Trp Tyr Arg Met Ser Pro Phe Asn Gln Thr
1 5 10
<210> 375
<211> 10
<212> PRT
<213> 智人
<400> 375
Trp Tyr Arg Met Ser Pro Pro Asn Gln Thr
1 5 10
<210> 376
<211> 10
<212> PRT
<213> 智人
<400> 376
Trp Tyr Arg Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 377
<211> 10
<212> PRT
<213> 智人
<400> 377
Trp Tyr Arg Met Ser Pro Thr Asn Gln Thr
1 5 10
<210> 378
<211> 10
<212> PRT
<213> 智人
<400> 378
Trp Tyr Arg Met Ser Pro Trp Asn Gln Thr
1 5 10
<210> 379
<211> 10
<212> PRT
<213> 智人
<400> 379
Trp Tyr Arg Met Ser Pro Tyr Asn Gln Thr
1 5 10
<210> 380
<211> 10
<212> PRT
<213> 智人
<400> 380
Trp Tyr Arg Met Ser Pro Val Asn Gln Thr
1 5 10
<210> 381
<211> 10
<212> PRT
<213> 智人
<400> 381
Trp Tyr Arg Met Ser Ala Ser Asn Gln Thr
1 5 10
<210> 382
<211> 10
<212> PRT
<213> 智人
<400> 382
Trp Tyr Arg Met Ser Arg Ser Asn Gln Thr
1 5 10
<210> 383
<211> 10
<212> PRT
<213> 智人
<400> 383
Trp Tyr Arg Met Ser Asn Ser Asn Gln Thr
1 5 10
<210> 384
<211> 10
<212> PRT
<213> 智人
<400> 384
Trp Tyr Arg Met Ser Asp Ser Asn Gln Thr
1 5 10
<210> 385
<211> 10
<212> PRT
<213> 智人
<400> 385
Trp Tyr Arg Met Ser Cys Ser Asn Gln Thr
1 5 10
<210> 386
<211> 10
<212> PRT
<213> 智人
<400> 386
Trp Tyr Arg Met Ser Gln Ser Asn Gln Thr
1 5 10
<210> 387
<211> 10
<212> PRT
<213> 智人
<400> 387
Trp Tyr Arg Met Ser Glu Ser Asn Gln Thr
1 5 10
<210> 388
<211> 10
<212> PRT
<213> 智人
<400> 388
Trp Tyr Arg Met Ser Gly Ser Asn Gln Thr
1 5 10
<210> 389
<211> 10
<212> PRT
<213> 智人
<400> 389
Trp Tyr Arg Met Ser His Ser Asn Gln Thr
1 5 10
<210> 390
<211> 10
<212> PRT
<213> 智人
<400> 390
Trp Tyr Arg Met Ser Ile Ser Asn Gln Thr
1 5 10
<210> 391
<211> 10
<212> PRT
<213> 智人
<400> 391
Trp Tyr Arg Met Ser Leu Ser Asn Gln Thr
1 5 10
<210> 392
<211> 10
<212> PRT
<213> 智人
<400> 392
Trp Tyr Arg Met Ser Lys Ser Asn Gln Thr
1 5 10
<210> 393
<211> 10
<212> PRT
<213> 智人
<400> 393
Trp Tyr Arg Met Ser Met Ser Asn Gln Thr
1 5 10
<210> 394
<211> 10
<212> PRT
<213> 智人
<400> 394
Trp Tyr Arg Met Ser Phe Ser Asn Gln Thr
1 5 10
<210> 395
<211> 10
<212> PRT
<213> 智人
<400> 395
Trp Tyr Arg Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 396
<211> 10
<212> PRT
<213> 智人
<400> 396
Trp Tyr Arg Met Ser Ser Ser Asn Gln Thr
1 5 10
<210> 397
<211> 10
<212> PRT
<213> 智人
<400> 397
Trp Tyr Arg Met Ser Thr Ser Asn Gln Thr
1 5 10
<210> 398
<211> 10
<212> PRT
<213> 智人
<400> 398
Trp Tyr Arg Met Ser Trp Ser Asn Gln Thr
1 5 10
<210> 399
<211> 10
<212> PRT
<213> 智人
<400> 399
Trp Tyr Arg Met Ser Tyr Ser Asn Gln Thr
1 5 10
<210> 400
<211> 10
<212> PRT
<213> 智人
<400> 400
Trp Tyr Arg Met Ser Val Ser Asn Gln Thr
1 5 10
<210> 401
<211> 10
<212> PRT
<213> 智人
<400> 401
Trp Tyr Arg Met Ala Pro Ser Asn Gln Thr
1 5 10
<210> 402
<211> 10
<212> PRT
<213> 智人
<400> 402
Trp Tyr Arg Met Arg Pro Ser Asn Gln Thr
1 5 10
<210> 403
<211> 10
<212> PRT
<213> 智人
<400> 403
Trp Tyr Arg Met Asn Pro Ser Asn Gln Thr
1 5 10
<210> 404
<211> 10
<212> PRT
<213> 智人
<400> 404
Trp Tyr Arg Met Asp Pro Ser Asn Gln Thr
1 5 10
<210> 405
<211> 10
<212> PRT
<213> 智人
<400> 405
Trp Tyr Arg Met Cys Pro Ser Asn Gln Thr
1 5 10
<210> 406
<211> 10
<212> PRT
<213> 智人
<400> 406
Trp Tyr Arg Met Gln Pro Ser Asn Gln Thr
1 5 10
<210> 407
<211> 10
<212> PRT
<213> 智人
<400> 407
Trp Tyr Arg Met Glu Pro Ser Asn Gln Thr
1 5 10
<210> 408
<211> 10
<212> PRT
<213> 智人
<400> 408
Trp Tyr Arg Met Gly Pro Ser Asn Gln Thr
1 5 10
<210> 409
<211> 10
<212> PRT
<213> 智人
<400> 409
Trp Tyr Arg Met His Pro Ser Asn Gln Thr
1 5 10
<210> 410
<211> 10
<212> PRT
<213> 智人
<400> 410
Trp Tyr Arg Met Ile Pro Ser Asn Gln Thr
1 5 10
<210> 411
<211> 10
<212> PRT
<213> 智人
<400> 411
Trp Tyr Arg Met Leu Pro Ser Asn Gln Thr
1 5 10
<210> 412
<211> 10
<212> PRT
<213> 智人
<400> 412
Trp Tyr Arg Met Lys Pro Ser Asn Gln Thr
1 5 10
<210> 413
<211> 10
<212> PRT
<213> 智人
<400> 413
Trp Tyr Arg Met Met Pro Ser Asn Gln Thr
1 5 10
<210> 414
<211> 10
<212> PRT
<213> 智人
<400> 414
Trp Tyr Arg Met Phe Pro Ser Asn Gln Thr
1 5 10
<210> 415
<211> 10
<212> PRT
<213> 智人
<400> 415
Trp Tyr Arg Met Pro Pro Ser Asn Gln Thr
1 5 10
<210> 416
<211> 10
<212> PRT
<213> 智人
<400> 416
Trp Tyr Arg Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 417
<211> 10
<212> PRT
<213> 智人
<400> 417
Trp Tyr Arg Met Thr Pro Ser Asn Gln Thr
1 5 10
<210> 418
<211> 10
<212> PRT
<213> 智人
<400> 418
Trp Tyr Arg Met Trp Pro Ser Asn Gln Thr
1 5 10
<210> 419
<211> 10
<212> PRT
<213> 智人
<400> 419
Trp Tyr Arg Met Tyr Pro Ser Asn Gln Thr
1 5 10
<210> 420
<211> 10
<212> PRT
<213> 智人
<400> 420
Trp Tyr Arg Met Val Pro Ser Asn Gln Thr
1 5 10
<210> 421
<211> 10
<212> PRT
<213> 智人
<400> 421
Trp Tyr Arg Ala Ser Pro Ser Asn Gln Thr
1 5 10
<210> 422
<211> 10
<212> PRT
<213> 智人
<400> 422
Trp Tyr Arg Arg Ser Pro Ser Asn Gln Thr
1 5 10
<210> 423
<211> 10
<212> PRT
<213> 智人
<400> 423
Trp Tyr Arg Asn Ser Pro Ser Asn Gln Thr
1 5 10
<210> 424
<211> 10
<212> PRT
<213> 智人
<400> 424
Trp Tyr Arg Asp Ser Pro Ser Asn Gln Thr
1 5 10
<210> 425
<211> 10
<212> PRT
<213> 智人
<400> 425
Trp Tyr Arg Cys Ser Pro Ser Asn Gln Thr
1 5 10
<210> 426
<211> 10
<212> PRT
<213> 智人
<400> 426
Trp Tyr Arg Gln Ser Pro Ser Asn Gln Thr
1 5 10
<210> 427
<211> 10
<212> PRT
<213> 智人
<400> 427
Trp Tyr Arg Glu Ser Pro Ser Asn Gln Thr
1 5 10
<210> 428
<211> 10
<212> PRT
<213> 智人
<400> 428
Trp Tyr Arg Gly Ser Pro Ser Asn Gln Thr
1 5 10
<210> 429
<211> 10
<212> PRT
<213> 智人
<400> 429
Trp Tyr Arg His Ser Pro Ser Asn Gln Thr
1 5 10
<210> 430
<211> 10
<212> PRT
<213> 智人
<400> 430
Trp Tyr Arg Ile Ser Pro Ser Asn Gln Thr
1 5 10
<210> 431
<211> 10
<212> PRT
<213> 智人
<400> 431
Trp Tyr Arg Leu Ser Pro Ser Asn Gln Thr
1 5 10
<210> 432
<211> 10
<212> PRT
<213> 智人
<400> 432
Trp Tyr Arg Lys Ser Pro Ser Asn Gln Thr
1 5 10
<210> 433
<211> 10
<212> PRT
<213> 智人
<400> 433
Trp Tyr Arg Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 434
<211> 10
<212> PRT
<213> 智人
<400> 434
Trp Tyr Arg Phe Ser Pro Ser Asn Gln Thr
1 5 10
<210> 435
<211> 10
<212> PRT
<213> 智人
<400> 435
Trp Tyr Arg Pro Ser Pro Ser Asn Gln Thr
1 5 10
<210> 436
<211> 10
<212> PRT
<213> 智人
<400> 436
Trp Tyr Arg Ser Ser Pro Ser Asn Gln Thr
1 5 10
<210> 437
<211> 10
<212> PRT
<213> 智人
<400> 437
Trp Tyr Arg Thr Ser Pro Ser Asn Gln Thr
1 5 10
<210> 438
<211> 10
<212> PRT
<213> 智人
<400> 438
Trp Tyr Arg Trp Ser Pro Ser Asn Gln Thr
1 5 10
<210> 439
<211> 10
<212> PRT
<213> 智人
<400> 439
Trp Tyr Arg Tyr Ser Pro Ser Asn Gln Thr
1 5 10
<210> 440
<211> 10
<212> PRT
<213> 智人
<400> 440
Trp Tyr Arg Val Ser Pro Ser Asn Gln Thr
1 5 10
<210> 441
<211> 10
<212> PRT
<213> 智人
<400> 441
Trp Tyr Ala Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 442
<211> 10
<212> PRT
<213> 智人
<400> 442
Trp Tyr Arg Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 443
<211> 10
<212> PRT
<213> 智人
<400> 443
Trp Tyr Asn Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 444
<211> 10
<212> PRT
<213> 智人
<400> 444
Trp Tyr Asp Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 445
<211> 10
<212> PRT
<213> 智人
<400> 445
Trp Tyr Cys Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 446
<211> 10
<212> PRT
<213> 智人
<400> 446
Trp Tyr Gln Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 447
<211> 10
<212> PRT
<213> 智人
<400> 447
Trp Tyr Glu Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 448
<211> 10
<212> PRT
<213> 智人
<400> 448
Trp Tyr Gly Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 449
<211> 10
<212> PRT
<213> 智人
<400> 449
Trp Tyr His Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 450
<211> 10
<212> PRT
<213> 智人
<400> 450
Trp Tyr Ile Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 451
<211> 10
<212> PRT
<213> 智人
<400> 451
Trp Tyr Leu Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 452
<211> 10
<212> PRT
<213> 智人
<400> 452
Trp Tyr Lys Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 453
<211> 10
<212> PRT
<213> 智人
<400> 453
Trp Tyr Met Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 454
<211> 10
<212> PRT
<213> 智人
<400> 454
Trp Tyr Phe Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 455
<211> 10
<212> PRT
<213> 智人
<400> 455
Trp Tyr Pro Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 456
<211> 10
<212> PRT
<213> 智人
<400> 456
Trp Tyr Ser Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 457
<211> 10
<212> PRT
<213> 智人
<400> 457
Trp Tyr Thr Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 458
<211> 10
<212> PRT
<213> 智人
<400> 458
Trp Tyr Trp Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 459
<211> 10
<212> PRT
<213> 智人
<400> 459
Trp Tyr Tyr Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 460
<211> 10
<212> PRT
<213> 智人
<400> 460
Trp Tyr Val Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 461
<211> 10
<212> PRT
<213> 智人
<400> 461
Trp Ala Arg Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 462
<211> 10
<212> PRT
<213> 智人
<400> 462
Trp Arg Arg Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 463
<211> 10
<212> PRT
<213> 智人
<400> 463
Trp Asn Arg Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 464
<211> 10
<212> PRT
<213> 智人
<400> 464
Trp Asp Arg Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 465
<211> 10
<212> PRT
<213> 智人
<400> 465
Trp Cys Arg Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 466
<211> 10
<212> PRT
<213> 智人
<400> 466
Trp Gln Arg Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 467
<211> 10
<212> PRT
<213> 智人
<400> 467
Trp Glu Arg Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 468
<211> 10
<212> PRT
<213> 智人
<400> 468
Trp Gly Arg Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 469
<211> 10
<212> PRT
<213> 智人
<400> 469
Trp His Arg Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 470
<211> 10
<212> PRT
<213> 智人
<400> 470
Trp Ile Arg Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 471
<211> 10
<212> PRT
<213> 智人
<400> 471
Trp Leu Arg Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 472
<211> 10
<212> PRT
<213> 智人
<400> 472
Trp Lys Arg Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 473
<211> 10
<212> PRT
<213> 智人
<400> 473
Trp Met Arg Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 474
<211> 10
<212> PRT
<213> 智人
<400> 474
Trp Phe Arg Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 475
<211> 10
<212> PRT
<213> 智人
<400> 475
Trp Pro Arg Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 476
<211> 10
<212> PRT
<213> 智人
<400> 476
Trp Ser Arg Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 477
<211> 10
<212> PRT
<213> 智人
<400> 477
Trp Thr Arg Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 478
<211> 10
<212> PRT
<213> 智人
<400> 478
Trp Trp Arg Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 479
<211> 10
<212> PRT
<213> 智人
<400> 479
Trp Tyr Arg Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 480
<211> 10
<212> PRT
<213> 智人
<400> 480
Trp Val Arg Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 481
<211> 10
<212> PRT
<213> 智人
<400> 481
Ala Tyr Arg Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 482
<211> 10
<212> PRT
<213> 智人
<400> 482
Arg Tyr Arg Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 483
<211> 10
<212> PRT
<213> 智人
<400> 483
Asn Tyr Arg Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 484
<211> 10
<212> PRT
<213> 智人
<400> 484
Asp Tyr Arg Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 485
<211> 10
<212> PRT
<213> 智人
<400> 485
Cys Tyr Arg Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 486
<211> 10
<212> PRT
<213> 智人
<400> 486
Gln Tyr Arg Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 487
<211> 10
<212> PRT
<213> 智人
<400> 487
Glu Tyr Arg Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 488
<211> 10
<212> PRT
<213> 智人
<400> 488
Gly Tyr Arg Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 489
<211> 10
<212> PRT
<213> 智人
<400> 489
His Tyr Arg Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 490
<211> 10
<212> PRT
<213> 智人
<400> 490
Ile Tyr Arg Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 491
<211> 10
<212> PRT
<213> 智人
<400> 491
Leu Tyr Arg Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 492
<211> 10
<212> PRT
<213> 智人
<400> 492
Lys Tyr Arg Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 493
<211> 10
<212> PRT
<213> 智人
<400> 493
Met Tyr Arg Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 494
<211> 10
<212> PRT
<213> 智人
<400> 494
Phe Tyr Arg Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 495
<211> 10
<212> PRT
<213> 智人
<400> 495
Pro Tyr Arg Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 496
<211> 10
<212> PRT
<213> 智人
<400> 496
Ser Tyr Arg Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 497
<211> 10
<212> PRT
<213> 智人
<400> 497
Thr Tyr Arg Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 498
<211> 10
<212> PRT
<213> 智人
<400> 498
Trp Tyr Arg Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 499
<211> 10
<212> PRT
<213> 智人
<400> 499
Tyr Tyr Arg Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 500
<211> 10
<212> PRT
<213> 智人
<400> 500
Val Tyr Arg Met Ser Pro Ser Asn Gln Thr
1 5 10
<210> 501
<211> 20
<212> PRT
<213> 智人
<400> 501
Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro
1 5 10 15
Gly Ser Thr Gly
20
<210> 502
<211> 20
<212> PRT
<213> 智人
<400> 502
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser
20
<210> 503
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 503
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
1 5 10 15
<210> 504
<211> 16
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 504
Gly Gly Gly Gly Ser Leu Val Pro Arg Gly Ser Gly Gly Gly Gly Ser
1 5 10 15
<210> 505
<211> 6
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 505
Gly Ser Gly Ser Gly Ser
1 5
<210> 506
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 506
Gly Ser Gly Ser Gly Ser Gly Ser
1 5
<210> 507
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 507
Gly Gly Gly Gly Ser Leu Val Pro Arg Gly Ser Gly Gly Gly
1 5 10
<210> 508
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 508
Gly Ser Gly Gly His Met Gly Ser Gly Gly
1 5 10
<210> 509
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 509
Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly
1 5 10
<210> 510
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 510
Gly Gly Ser Gly Gly
1 5
<210> 511
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 511
Gly Gly Ser Gly Gly Gly Gly Gly
1 5
<210> 512
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 512
Gly Gly Gly Ser Glu Gly Gly Gly Ser Glu Gly Gly Gly Ser Glu Gly
1 5 10 15
Gly Gly
<210> 513
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 513
Ala Ala Gly Ala Ala Thr Ala Ala
1 5
<210> 514
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 514
Gly Gly Gly Gly Gly
1 5
<210> 515
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 515
Gly Gly Ser Ser Gly
1 5
<210> 516
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 516
Gly Ser Gly Gly Gly Thr Gly Gly Gly Ser Gly
1 5 10
<210> 517
<211> 2
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 517
Gly Thr
1
<210> 518
<211> 26
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 518
Gly Ser Gly Ser Gly Ser Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly
1 5 10 15
Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser
20 25
<210> 519
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 519
Gly Ser Gly Gly Ser Gly Ser Gly Gly Ser Gly Gly Ser Gly
1 5 10
<210> 520
<211> 22
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 520
Val Lys Gln Thr Leu Asn Phe Asp Leu Leu Lys Leu Ala Gly Asp Val
1 5 10 15
Glu Ser Asn Pro Gly Pro
20
<210> 521
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 521
Gln Cys Thr Asn Tyr Ala Leu Leu Lys Leu Ala Gly Asp Val Glu Ser
1 5 10 15
Asn Pro Gly Pro
20
<210> 522
<211> 19
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 522
Ala Thr Asn Phe Ser Leu Leu Lys Gln Ala Gly Asp Val Glu Glu Asn
1 5 10 15
Pro Gly Pro
<210> 523
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 523
His Tyr Ala Gly Tyr Phe Ala Asp Leu Leu Ile His Asp Ile Glu Thr
1 5 10 15
Asn Pro Gly Pro
20
<210> 524
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 524
Gly Ile Phe Asn Ala His Tyr Ala Gly Tyr Phe Ala Asp Leu Leu Ile
1 5 10 15
His Asp Ile Glu Thr Asn Pro Gly Pro
20 25
<210> 525
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 525
Lys Ala Val Arg Gly Tyr His Ala Asp Tyr Tyr Lys Gln Arg Leu Ile
1 5 10 15
His Asp Val Glu Met Asn Pro Gly Pro
20 25
<210> 526
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 526
Gly Ala Thr Asn Phe Ser Leu Leu Lys Leu Ala Gly Asp Val Glu Leu
1 5 10 15
Asn Pro Gly Pro
20
<210> 527
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 527
Glu Gly Arg Gly Ser Leu Leu Thr Cys Gly Asp Val Glu Glu Asn Pro
1 5 10 15
Gly Pro
<210> 528
<211> 19
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 528
Ala Ala Arg Gln Met Leu Leu Leu Leu Ser Gly Asp Val Glu Thr Asn
1 5 10 15
Pro Gly Pro
<210> 529
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 529
Phe Leu Arg Lys Arg Thr Gln Leu Leu Met Ser Gly Asp Val Glu Ser
1 5 10 15
Asn Pro Gly Pro
20
<210> 530
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 530
Gly Ser Trp Thr Asp Ile Leu Leu Leu Leu Ser Gly Asp Val Glu Thr
1 5 10 15
Asn Pro Gly Pro
20
<210> 531
<211> 19
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 531
Thr Arg Ala Glu Glu Asp Glu Leu Ile Arg Ala Gly Ile Glu Ser Asn
1 5 10 15
Pro Gly Pro
<210> 532
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 532
Ala Lys Phe Gln Ile Asp Lys Ile Leu Ile Ser Gly Asp Val Glu Leu
1 5 10 15
Asn Pro Gly Pro
20
<210> 533
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 533
Ser Lys Phe Gln Ile Asp Lys Ile Leu Ile Ser Gly Asp Ile Glu Leu
1 5 10 15
Asn Pro Gly Pro
20
<210> 534
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 534
Ser Ser Ile Ile Arg Thr Lys Met Leu Val Ser Gly Asp Val Glu Glu
1 5 10 15
Asn Pro Gly Pro
20
<210> 535
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 535
Cys Asp Ala Gln Arg Gln Lys Leu Leu Leu Ser Gly Asp Ile Glu Gln
1 5 10 15
Asn Pro Gly Pro
20
<210> 536
<211> 668
<212> DNA
<213> 人工序列
<220>
<223> 合成序列
<400> 536
gcgatctgac ggttcactaa acgagctctg cttatatagg cctcccaccg tacacgccac 60
ctcgacatac tcgagtagtt attaatagta atcaattacg gggtcattag ttcatagccc 120
atatatggag ttccgcgtta cataacttac ggtaaatggc ccgcctggct gaccgcccaa 180
cgacccccgc ccattgacgt caataatgac gtatgttccc atagtaacgc caatagggac 240
tttccattga cgtcaatggg tggagtattt acggtaaact gcccacttgg cagtacatca 300
agtgtatcat atgccaagta cgccccctat tgacgtcaat gacggtaaat ggcccgcctg 360
gcattatgcc cagtacatga ccttatggga ctttcctact tggcagtaca tctacgtatt 420
agtcatcgct attaccatgg tgatgcggtt ttggcagtac atcaatgggc gtggatagcg 480
gtttgactca cggggatttc caagtctcca ccccattgac gtcaatggga gtttgttttg 540
gcaccaaaat caacgggact ttccaaaatg tcgtaacaac tccgccccat tgacgcaaat 600
gggcggtagg cgtgtacggt gggaggtcta tataagcaga gctggtttag tgaaccgtca 660
gatccgct 668
<210> 537
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 537
Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro
1 5 10 15
Gly Ser Thr Gly Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly
20 25 30
Gln Phe
<210> 538
<211> 59
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 538
Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro
1 5 10 15
Gly Ser Thr Gly Glu Tyr Arg Met Ser Pro Ser Asn Gln Thr Gly Gly
20 25 30
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Thr Ala His
35 40 45
Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
50 55
<210> 539
<211> 59
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 539
Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro
1 5 10 15
Gly Ser Thr Gly Tyr Tyr Arg Met Ser Pro Ser Asn Gln Thr Gly Gly
20 25 30
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Thr Ala His
35 40 45
Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
50 55
<210> 540
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 540
Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro
1 5 10 15
Gly Ser Thr Gly Thr Arg Tyr Pro Ser Pro Ser Pro Lys Pro Glu Gly
20 25 30
Arg Phe
<210> 541
<211> 59
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 541
Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro
1 5 10 15
Gly Ser Thr Gly Trp Asn Arg Leu Ser Pro Ser Asn Gln Thr Gly Gly
20 25 30
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Thr Arg Tyr
35 40 45
Pro Ser Pro Ser Pro Lys Pro Glu Gly Arg Phe
50 55
<210> 542
<211> 107
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 542
Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro
1 5 10 15
Gly Ser Thr Gly Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly
20 25 30
Gln Phe Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
35 40 45
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe Gly Gly
50 55 60
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Tyr Arg
65 70 75 80
Met Ser Pro Ser Asn Gln Thr Glu Tyr Arg Met Ser Pro Ser Asn Gln
85 90 95
Thr Glu Tyr Arg Met Ser Pro Ser Asn Gln Thr
100 105
<210> 543
<211> 107
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 543
Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro
1 5 10 15
Gly Ser Thr Gly Glu Tyr Arg Met Ser Pro Ser Asn Gln Thr Glu Tyr
20 25 30
Arg Met Ser Pro Ser Asn Gln Thr Glu Tyr Arg Met Ser Pro Ser Asn
35 40 45
Gln Thr Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
50 55 60
Ser Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe Thr
65 70 75 80
Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe Thr Ala His
85 90 95
Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
100 105
<210> 544
<211> 231
<212> PRT
<213> 智人
<400> 544
Ile Ser Ala Met Val Arg Ser Pro Pro Cys Pro Ser Cys Pro Ala Pro
1 5 10 15
Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
20 25 30
Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val
35 40 45
Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp
50 55 60
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe
65 70 75 80
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp
85 90 95
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu
100 105 110
Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg
115 120 125
Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys
130 135 140
Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp
145 150 155 160
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys
165 170 175
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser
180 185 190
Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser
195 200 205
Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser
210 215 220
Leu Ser Leu Ser Pro Gly Lys
225 230
<210> 545
<211> 229
<212> PRT
<213> 小鼠
<400> 545
Ile Ser Ala Met Val Arg Ser Gly Cys Lys Pro Cys Ile Cys Thr Val
1 5 10 15
Pro Glu Val Ser Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val
20 25 30
Leu Thr Ile Thr Leu Thr Pro Lys Val Thr Cys Val Val Val Asp Ile
35 40 45
Ser Lys Asp Asp Pro Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val
50 55 60
Glu Val His Thr Ala Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser
65 70 75 80
Thr Phe Arg Ser Val Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu
85 90 95
Asn Gly Lys Glu Phe Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala
100 105 110
Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro
115 120 125
Gln Val Tyr Thr Ile Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys
130 135 140
Val Ser Leu Thr Cys Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr
145 150 155 160
Val Glu Trp Gln Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr
165 170 175
Gln Pro Ile Met Asp Thr Asp Gly Ser Tyr Phe Val Tyr Ser Lys Leu
180 185 190
Asn Val Gln Lys Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser
195 200 205
Val Leu His Glu Gly Leu His Asn His His Thr Glu Lys Ser Leu Ser
210 215 220
His Ser Pro Gly Lys
225
<210> 546
<211> 265
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 546
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly
20 25 30
Gln Phe Ile Ser Ala Met Val Arg Ser Pro Pro Cys Pro Ser Cys Pro
35 40 45
Ala Pro Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
50 55 60
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
65 70 75 80
Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr
85 90 95
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
100 105 110
Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
115 120 125
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
130 135 140
Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
145 150 155 160
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met
165 170 175
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
180 185 190
Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn
195 200 205
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
210 215 220
Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val
225 230 235 240
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
245 250 255
Lys Ser Leu Ser Leu Ser Pro Gly Lys
260 265
<210> 547
<211> 290
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 547
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Glu Tyr Arg Met Ser Pro Ser Asn Gln Thr Gly Gly
20 25 30
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Thr Ala His
35 40 45
Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe Ile Ser Ala Met Val
50 55 60
Arg Ser Pro Pro Cys Pro Ser Cys Pro Ala Pro Glu Phe Leu Gly Gly
65 70 75 80
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
85 90 95
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu
100 105 110
Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
115 120 125
Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg
130 135 140
Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
145 150 155 160
Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu
165 170 175
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
180 185 190
Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu
195 200 205
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
210 215 220
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
225 230 235 240
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp
245 250 255
Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His
260 265 270
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
275 280 285
Gly Lys
290
<210> 548
<211> 290
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 548
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Tyr Tyr Arg Met Ser Pro Ser Asn Gln Thr Gly Gly
20 25 30
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Thr Ala His
35 40 45
Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe Ile Ser Ala Met Val
50 55 60
Arg Ser Pro Pro Cys Pro Ser Cys Pro Ala Pro Glu Phe Leu Gly Gly
65 70 75 80
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
85 90 95
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu
100 105 110
Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
115 120 125
Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg
130 135 140
Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
145 150 155 160
Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu
165 170 175
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
180 185 190
Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu
195 200 205
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
210 215 220
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
225 230 235 240
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp
245 250 255
Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His
260 265 270
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
275 280 285
Gly Lys
290
<210> 549
<211> 263
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 549
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Thr Arg Tyr Pro Ser Pro Ser Pro Lys Pro Glu Gly
20 25 30
Arg Phe Ile Ser Ala Met Val Arg Ser Gly Cys Lys Pro Cys Ile Cys
35 40 45
Thr Val Pro Glu Val Ser Ser Val Phe Ile Phe Pro Pro Lys Pro Lys
50 55 60
Asp Val Leu Thr Ile Thr Leu Thr Pro Lys Val Thr Cys Val Val Val
65 70 75 80
Asp Ile Ser Lys Asp Asp Pro Glu Val Gln Phe Ser Trp Phe Val Asp
85 90 95
Asp Val Glu Val His Thr Ala Gln Thr Gln Pro Arg Glu Glu Gln Phe
100 105 110
Asn Ser Thr Phe Arg Ser Val Ser Glu Leu Pro Ile Met His Gln Asp
115 120 125
Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg Val Asn Ser Ala Ala Phe
130 135 140
Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Arg Pro Lys
145 150 155 160
Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro Lys Glu Gln Met Ala Lys
165 170 175
Asp Lys Val Ser Leu Thr Cys Met Ile Thr Asp Phe Phe Pro Glu Asp
180 185 190
Ile Thr Val Glu Trp Gln Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys
195 200 205
Asn Thr Gln Pro Ile Met Asp Thr Asp Gly Ser Tyr Phe Val Tyr Ser
210 215 220
Lys Leu Asn Val Gln Lys Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr
225 230 235 240
Cys Ser Val Leu His Glu Gly Leu His Asn His His Thr Glu Lys Ser
245 250 255
Leu Ser His Ser Pro Gly Lys
260
<210> 550
<211> 288
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 550
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Trp Asn Arg Leu Ser Pro Ser Asn Gln Thr Gly Gly
20 25 30
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Thr Arg Tyr
35 40 45
Pro Ser Pro Ser Pro Lys Pro Glu Gly Arg Phe Ile Ser Ala Met Val
50 55 60
Arg Ser Gly Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser Ser
65 70 75 80
Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu
85 90 95
Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro
100 105 110
Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His Thr Ala
115 120 125
Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val
130 135 140
Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe
145 150 155 160
Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr
165 170 175
Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile
180 185 190
Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys
195 200 205
Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp
210 215 220
Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp
225 230 235 240
Thr Asp Gly Ser Tyr Phe Val Tyr Ser Lys Leu Asn Val Gln Lys Ser
245 250 255
Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly
260 265 270
Leu His Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys
275 280 285
<210> 551
<211> 1335
<212> DNA
<213> 智人
<400> 551
gagtaattca tacaaaagga ctcgcccctg ccttggggaa tcccagggac cgtcgttaaa 60
ctcccactaa cgtagaaccc agagatcgct gcgttcccgc cccctcaccc gcccgctctc 120
gtcatcactg aggtggagaa gagcatgcgt gaggctccgg tgcccgtcag tgggcagagc 180
gcacatcgcc cacagtcccc gagaagttgg ggggaggggt cggcaattga accggtgcct 240
agagaaggtg gcgcggggta aactgggaaa gtgatgtcgt gtactggctc cgcctttttc 300
ccgagggtgg gggagaaccg tatataagtg cagtagtcgc cgtgaacgtt ctttttcgca 360
acgggtttgc cgccagaaca caggtaagtg ccgtgtgtgg ttcccgcggg cctggcctct 420
ttacgggtta tggcccttgc gtgccttgaa ttacttccac gcccctggct gcagtacgtg 480
attcttgatc ccgagcttcg ggttggaagt gggtgggaga gttcgaggcc ttgcgcttaa 540
ggagcccctt cgcctcgtgc ttgagttgag gcctggcttg ggcgctgggg ccgccgcgtg 600
cgaatctggt ggcaccttcg cgcctgtctc gctgctttcg ataagtctct agccatttaa 660
aatttttgat gacctgctgc gacgcttttt ttctggcaag atagtcttgt aaatgcgggc 720
caagatctgc acactggtat ttcggttttt ggggccgcgg gcggcgacgg ggcccgtgcg 780
tcccagcgca catgttcggc gaggcggggc ctgcgagcgc ggccaccgag aatcggacgg 840
gggtagtctc aagctggccg gcctgctctg gtgcctggcc tcgcgccgcc gtgtatcgcc 900
ccgccctggg cggcaaggct ggcccggtcg gcaccagttg cgtgagcgga aagatggccg 960
cttcccggcc ctgctgcagg gagctcaaaa tggaggacgc ggcgctcggg agagcgggcg 1020
ggtgagtcac ccacacaaag gaaaagggcc tttccgtcct cagccgtcgc ttcatgtgac 1080
tccacggagt accgggcgcc gtccaggcac ctcgattagt tctcgagctt ttggagtacg 1140
tcgtctttag gttgggggga ggggttttat gcgatggagt ttccccacac tgagtgggtg 1200
gagactgaag ttaggccagc ttggcacttg atgtaattct ccttggaatt tgcccttttt 1260
gagtttggat cttggttcat tctcaagcct cagacagtgg ttcaaagttt ttttcttcca 1320
tttcaggtgt cgtga 1335
<210> 552
<211> 601
<212> DNA
<213> 人工序列
<220>
<223> 合成序列
<400> 552
cctctccccc ccccccctct ccctcccccc cccctaacgt tactggccga agccgcttgg 60
aataaggccg gtgtgcgttt gtctatatgt tattttccac catattgccg tcttttggca 120
atgtgagggc ccggaaacct ggccctgtct tcttgacgag cattcctagg ggtctttccc 180
ctctcgccaa aggaatgcaa ggtctgttga atgtcgtgaa ggaagcagtt cctctggaag 240
cttcttgaag acaaacaacg tctgtagcga ccctttgcag gcagcggaac cccccacctg 300
gcgacaggtg cctctgcggc caaaagccac gtgtataaga tacacctgca aaggcggcac 360
aaccccagtg ccacgttgtg agttggatag ttgtggaaag agtcaaatgg ctctcctcaa 420
gcgtattcaa caaggggctg aaggatgccc agaaggtacc ccattgtatg ggatctgatc 480
tggggcctcg gtgcacatgc tttacatgtg tttagtcgag gttaaaaaaa cgtctaggcc 540
ccccgaacca cggggacgtg gttttccttt gaaaaacacg atgataagct tgccacaacc 600
c 601
<210> 553
<211> 536
<212> DNA
<213> 人巨细胞病毒
<400> 553
ccgcgttaca taacttacgg taaatggccc gcctggctga ccgcccaacg acccccgccc 60
attgacgtca ataatgacgt atgttcccat agtaacgcca atagggactt tccattgacg 120
tcaatgggtg gagtatttac ggtaaactgc ccacttggca gtacatcaag tgtatcatat 180
gccaagtacg ccccctattg acgtcaatga cggtaaatgg cccgcctggc attatgccca 240
gtacatgacc ttatgggact ttcctacttg gcagtacatc tacgtattag tcatcgctat 300
taccatggtg atgcggtttt ggcagtacat caatgggcgt ggatagcggt ttgactcacg 360
gggatttcca agtctccacc ccattgacgt caatgggagt ttgttttggc accaaaatca 420
acgggacttt ccaaaatgtc gtaacaactc cgccccattg acgcaaatgg gcggtaggcg 480
tgtacggtgg gaggtctata taagcagagc tggtttagtg aaccgtcaga tccgct 536
<210> 554
<211> 22
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 554
Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln Ala Gly Asp Val
1 5 10 15
Glu Glu Asn Pro Gly Pro
20
<210> 555
<211> 1433
<212> DNA
<213> 人工序列
<220>
<223> 合成序列
<400> 555
atgtcgggcg tcgggggaga gggagttccc tctgcgcttg cgattctagc ctcgtggggc 60
tggacgttcg acacgccaaa ccacgagtcg gggatatcgc cagatacgac tcccgcagat 120
tccattcggg gtgccgctgt ggcctcacct gaccaacctt tacacggggg cccggaacgg 180
gaggccacag cgccgtcttt ctccccaacg cgcgcggatg acggcccgcc ctgtaccgac 240
gggccctacg tgacgtttga taccctgttt atggtgtcgt cgatcgacga attagggcgt 300
cgccagctca cggacaccat ccgcaaggac ctgcggttgt cgctggccaa gtttagcatt 360
gcgtgcacca agacctcctc gttttcggga aacgccccgc gccaccacag acgcggggcg 420
ttccagcgcg gcacgcgggc gccgcgcagc aacaaaagcc tccagatgtt tgtgttgtgc 480
aaacgcgccc acgccgctcg agtgcgagag cagcttcggg tcgttattca gtcccgcaag 540
ccgcgcaagt attacacgcg atcttcggac gggcggctct gccccgccgt ccccgtgttc 600
gtccacgagt tcgtctcgtc cgagccaatg cgcctccacc gagataacgt catgctggcc 660
tcgggggccg agtaaccgcc ccccccccat gccaccctca ctgcccgtcg cgcgtgtttg 720
atgttaataa ataacacata aatttggctg gttgtttgtt gtctttaatg gaccgcccgc 780
aagggggggg gggcatttca gtgtcgggtg acgagcgcga tccggccggg atcctaggac 840
cccaaaagtt tgtctgcgta ttccagggcg gggctcagtt gaatctcccg cagcacctct 900
accagcaggt ccgcggtggg ctggagaaac tcggccgtcc cggggcaggc ggttgtcggg 960
ggtggaggcg cggcgcccac cccgtgtgcc gcgcctggcg tctcctctgg gggcgacccg 1020
taaatggttg cagtgatgta aatggtgtcc gcggtccaga ccacggtcaa aatgccggcc 1080
gtggcgctcc gggcgctttc gccgcgcgag gagctgaccc aggagtcgaa cggatacgcg 1140
tacatatggg cgtcccaccc gcgttcgagc ttctggttgc tgtcccggcc tataaagcgg 1200
taggcacaaa attcggcgcg acagtcgata atcaccaaca gcccaatggg ggtgtgctgg 1260
ataacaacgc ctccgcgcgg caggcggtcc tggcgctccc ggccccgtac catgatcgcg 1320
cgggtgccgt actcaaaaac atgcaccacc tgcgcggcgt cgggcagtgc gctggtcagc 1380
gaggccctgg cgtggcatag gctatacgcg atggtcgtct gtggattgga cat 1433
<210> 556
<211> 1533
<212> DNA
<213> 人工序列
<220>
<223> 合成序列
<400> 556
ggccctcaat ccctaataca tttcagtgat ggggtagtcc agtgagccac atttgttgcc 60
ttgttcagca cgcactctgt cagggagctg gtgccggcct tccgcttgaa gccagagttg 120
cagatgtatc tctcccggga atacaggctg taagacttca cccagatgtc tgcgtgctcc 180
acgctcattg gaggtgggca ggtgatgccc cttgtagcgg ggggtctcag cagcagcagc 240
agcagcaggg caggcagtcc cagggtccga catcctctag cgcggcgtgg agccatggtg 300
gcgaattctc caggcgatct gacggttcac taaacgagct ctgcttatat aggcctccca 360
ccgtacacgc cacctcgaca tactcgagta gttattaata gtaatcaatt acggggtcat 420
tagttcatag cccatatatg gagttccgcg ttacataact tacggtaaat ggcccgcctg 480
gctgaccgcc caacgacccc cgcccattga cgtcaataat gacgtatgtt cccatagtaa 540
cgccaatagg gactttccat tgacgtcaat gggtggagta tttacggtaa actgcccact 600
tggcagtaca tcaagtgtat catatgccaa gtacgccccc tattgacgtc aatgacggta 660
aatggcccgc ctggcattat gcccagtaca tgaccttatg ggactttcct acttggcagt 720
acatctacgt attagtcatc gctattacca tggtgatgcg gttttggcag tacatcaatg 780
ggcgtggata gcggtttgac tcacggggat ttccaagtct ccaccccatt gacgtcaatg 840
ggagtttgtt ttggcaccaa aatcaacggg actttccaaa atgtcgtaac aactccgccc 900
cattgacgca aatgggcggt aggcgtgtac ggtgggaggt ctatataagc agagctggtt 960
tagtgaaccg tcagatccgc tagggatcct ctagtcagct gacgcgtgct agcgcggccg 1020
catcgataag cttgccacca tgcggatttc caagccccat ctgcgctcca tttccatcca 1080
gtgttacctg tgcctgctgc tgaatagcca ttttctgacc gaagccggca tccacgtgtt 1140
catcctgggc tgcttttccg ccggcctgcc aaagaccgag gcaaactggg tgaatgtgat 1200
ctctgacctg aagaagatcg aggatctgat ccagagcatg cacatcgacg ccaccctgta 1260
cacagagtcc gatgtgcacc cttcttgcaa ggtgacagcc atgaagtgtt tcctgctgga 1320
gctgcaggtc atctctctgg agagcggcga cgcctctatc cacgataccg tggagaacct 1380
gatcatcctg gccaacaata gcctgagctc caacggcaat gtgacagagt ccggctgcaa 1440
ggagtgtgag gagctggagg agaagaatat caaagagttc ctgcagagtt tcgtccatat 1500
cgtccagatg tttatcaata cttcctaagt cga 1533
<210> 557
<211> 2304
<212> DNA
<213> 人工序列
<220>
<223> 合成序列
<400> 557
ggcccttaca gatggtgact acagttttcc aggtcctcgt ctcttgatga agttccccag 60
gtgacgggca gggcctccat ggcctccatc tccacagagg ccagaggggg ggtctgtctg 120
gacttcagat aacaggccag cagggacacg gcgctcaggc cgcacagcag cactgtagag 180
gtggagatgg ccactgtggt gtcggagtgg ccctgtgggt acacgcctgg aggctggtgg 240
ctggcagatg ctgtcagctc ccaattcttg gctgtggtct gagaaggggt gccgtggcta 300
gactcgtggg agctgatctc tgtggtgcct gtggatgggc tcttagaagg catcagctgg 360
gagccaggca cgattgctgc tgtggttgct gcggtattgt tagaggatgg gctagatgct 420
gcaggctcct tgccggatgg gctcagagac tctggctgtg gtgtcacgcc ggctgtggtc 480
acggtgctgg gtggtgcggg ccgctggtgc accagggcgg gatcccggat gcacttcaga 540
gagggtgtgg tccagtgggc cacattggtg gccttgttca gcacgcactc tgtcagggag 600
ctggtgccgg ccttcctctt aaagccgctg ttgcagatgt atctctcccg agaatacagg 660
gagtagctct tcacccagat gtcggcgtgc tccacggaca tagggggtgg acatgtgatg 720
cctgcctgct gtctgctggt ccggtggtgg tgacactggg ggcaattctc cattgtcctc 780
agcctcacgc atgcctcgtg ggtctgcacc tcgtggttga aagactcgga gattctgctc 840
cggcctgcca gcacggccag gcgatccctt gcgtcgcgtg ttgcaggggg cctcagcagc 900
agcagtaata acagggcggg caggcccagg gtgcgacagc ccctggctct ccttggtgcc 960
attgctgctg ctccgcagga cacggcgggt gagccgggtc ttgcgctgcc cagtccgggt 1020
ggtggagggg atctctgttc ggggacctgt cttcctgcca gtctcatggt ggcgaattct 1080
ccaggcgatc tgacggttca ctaaacgagc tctgcttata taggcctccc accgtacacg 1140
ccacctcgac atactcgagt agttattaat agtaatcaat tacggggtca ttagttcata 1200
gcccatatat ggagttccgc gttacataac ttacggtaaa tggcccgcct ggctgaccgc 1260
ccaacgaccc ccgcccattg acgtcaataa tgacgtatgt tcccatagta acgccaatag 1320
ggactttcca ttgacgtcaa tgggtggagt atttacggta aactgcccac ttggcagtac 1380
atcaagtgta tcatatgcca agtacgcccc ctattgacgt caatgacggt aaatggcccg 1440
cctggcatta tgcccagtac atgaccttat gggactttcc tacttggcag tacatctacg 1500
tattagtcat cgctattacc atggtgatgc ggttttggca gtacatcaat gggcgtggat 1560
agcggtttga ctcacgggga tttccaagtc tccaccccat tgacgtcaat gggagtttgt 1620
tttggcacca aaatcaacgg gactttccaa aatgtcgtaa caactccgcc ccattgacgc 1680
aaatgggcgg taggcgtgta cggtgggagg tctatataag cagagctggt ttagtgaacc 1740
gtcagatccg ctagggatcc tctagtcagc tgacgcgtgc tagcgcggcc gcatcgataa 1800
gcttgccacc atgcggattt ccaagcccca tctgcgctcc atttccatcc agtgttacct 1860
gtgcctgctg ctgaatagcc attttctgac cgaagccggc atccacgtgt tcatcctggg 1920
ctgcttttcc gccggcctgc caaagaccga ggcaaactgg gtgaatgtga tctctgacct 1980
gaagaagatc gaggatctga tccagagcat gcacatcgac gccaccctgt acacagagtc 2040
cgatgtgcac ccttcttgca aggtgacagc catgaagtgt ttcctgctgg agctgcaggt 2100
catctctctg gagagcggcg acgcctctat ccacgatacc gtggagaacc tgatcatcct 2160
ggccaacaat agcctgagct ccaacggcaa tgtgacagag tccggctgca aggagtgtga 2220
ggagctggag gagaagaata tcaaagagtt cctgcagagt ttcgtccata tcgtccagat 2280
gtttatcaat acttcctaag tcga 2304
<210> 558
<211> 1842
<212> DNA
<213> 人工序列
<220>
<223> 合成序列
<400> 558
ggcccttatt tttccagtgc ggacacctct ttttccaggg ctgacacctc cttttccagg 60
gctgagactt ctttttccag ggcagacacc tccttctcca gggcagacac ctcggagccg 120
ccgccgccgg atcctcctcc tccgcttcct cctcctccat cccggataca cttcagggag 180
ggtgtggtcc agtgggccac atttgtggcc ttgttcagca cgcactctgt cagggagctg 240
gtgccggcct tcctcttgaa gccgctgttg cagatgtatc tctcccgaga atacaggctg 300
taagacttca cccagatgtc tgcgtgctcc acgctcattg gaggtgggca ggtgatgccc 360
cttgtagcag gtggtctcag cagcagcagc agcagcaggg caggcagtcc cagtgtgcga 420
catcctcggg ctcttctagg ggccatggtg gcgaattctc caggcgatct gacggttcac 480
taaacgagct ctgcttatat aggcctccca ccgtacacgc cacctcgaca tactcgagta 540
gttattaata gtaatcaatt acggggtcat tagttcatag cccatatatg gagttccgcg 600
ttacataact tacggtaaat ggcccgcctg gctgaccgcc caacgacccc cgcccattga 660
cgtcaataat gacgtatgtt cccatagtaa cgccaatagg gactttccat tgacgtcaat 720
gggtggagta tttacggtaa actgcccact tggcagtaca tcaagtgtat catatgccaa 780
gtacgccccc tattgacgtc aatgacggta aatggcccgc ctggcattat gcccagtaca 840
tgaccttatg ggactttcct acttggcagt acatctacgt attagtcatc gctattacca 900
tggtgatgcg gttttggcag tacatcaatg ggcgtggata gcggtttgac tcacggggat 960
ttccaagtct ccaccccatt gacgtcaatg ggagtttgtt ttggcaccaa aatcaacggg 1020
actttccaaa atgtcgtaac aactccgccc cattgacgca aatgggcggt aggcgtgtac 1080
ggtgggaggt ctatataagc agagctggtt tagtgaaccg tcagatccgc tagggatcct 1140
ctagtcagct gacgcgtgct agcgcggccg catcgataag cttgccacca tgcggatttc 1200
caaacctcac ctgcgatcta tctccatcca gtgctatctg tgcctgctgc tgaactctca 1260
tttcctgacc gaagccggca tccacgtgtt catcctgggc tgctttagcg ccggcctgcc 1320
aaagaccgag gcaaactggg tgaatgtgat ctctgacctg aagaagatcg aggatctgat 1380
ccagagcatg cacatcgacg ccaccctgta cacagagtcc gatgtgcacc cttcttgcaa 1440
ggtgacagcc atgaagtgtt tcctgctgga gctgcaggtc atctctctgg agagcggcga 1500
cgcctccatc cacgataccg tggagaacct gatcatcctg gccaacaata gcctgagctc 1560
caacggcaat gtgacagagt ccggctgcaa ggagtgtgag gagctggagg agaagaacat 1620
caaggagttc ctgcagtctt ttgtgcacat cgtgcagatg tttatcaata ccagcggagg 1680
aggaggatcc ggcggaggag gctctggcgg cggcggcagc tgtggcggca aggtgtccgc 1740
cctgaaggag aaggtgtctg ccctgaagga aaaagtgtcc gctctgaagg aaaaggtgtc 1800
cgcactgaaa gaaaaggtct ccgccctgaa ggaataagtc ga 1842
<210> 559
<211> 2613
<212> DNA
<213> 人工序列
<220>
<223> 合成序列
<400> 559
ggcccttatt tttccagtgc ggacacctct ttttccagtg ctgacacctc cttctccagg 60
gctgacactt ctttttccag ggcgctcacc tctttttcca gggcagacac ctcggagccg 120
ccgccgccgg agcctcctcc tccgcttcct cctcctccca ggtggtggga acaattctcc 180
agatcctcgt cgcgagagga tgtgccccag gtcactggca gggcctccat tgcctccatc 240
tccacagatg ccagaggtgg ggtctgcctg gacttcagat aacaggccag caggctcacg 300
gcagacaggc cgcacagcag cactgtggag gtgctgatgg ccactgtggt gtcggagtgg 360
ccctgtgggt acacgcctgg aggctggtga gaggcggatg ctgtcagctc ccagttcttg 420
gctgtggtct gagaaggggt gccgtggcta gactcgtggg agctgatctc tgtggtgccg 480
gtgcttggag acttggaagg catcagctgg gagccaggca cgattgctgc tgtggttgct 540
gcggtattgt tagaggatgg gctagatgct gcaggctcct tgccgcttgg agacagggac 600
tctggctgtg gtgtcactcc tgctgtggtc acggtgctgg gtggtgcggg ccgctggtgc 660
accagggcgg gatcccggat gcacttcaga gagggtgtgg tccagtgggc cacattggtg 720
gccttgttca gcacgcactc tgtcagggag ctggtgccgg ccttccgctt aaagccgctg 780
ttgcagatgt atctctcccg agaatacagg ctgtaagact tcacccagat gtcggcgtgc 840
tccacggaca tagggggtgg acatgtgatg cctgcctgct gtctgctggt ccggtggtgg 900
tgacactggg ggcaattctc cattgtcctc agcctcacgc atgcctcgtg ggtctgcacc 960
tcgtggttga aggactcgct gattctgctc cggcctgcca gcacggccag gcgatccctt 1020
gcgtcgcgtg ttgcaggggg cctcagcagc agcagtaata acagggcggg caggcccagg 1080
gtgcgacagc ccctggctct ccttggtgcc attgctgctg ctccgcagga cacagcggga 1140
ctgccgggtc ttgcactgcc cagcccagga ggaggagggg atctctgctc ggggacctgc 1200
cttccagcca gccgcatggt ggcgaattct ccaggcgatc tgacggttca ctaaacgagc 1260
tctgcttata taggcctccc accgtacacg ccacctcgac atactcgagt agttattaat 1320
agtaatcaat tacggggtca ttagttcata gcccatatat ggagttccgc gttacataac 1380
ttacggtaaa tggcccgcct ggctgaccgc ccaacgaccc ccgcccattg acgtcaataa 1440
tgacgtatgt tcccatagta acgccaatag ggactttcca ttgacgtcaa tgggtggagt 1500
atttacggta aactgcccac ttggcagtac atcaagtgta tcatatgcca agtacgcccc 1560
ctattgacgt caatgacggt aaatggcccg cctggcatta tgcccagtac atgaccttat 1620
gggactttcc tacttggcag tacatctacg tattagtcat cgctattacc atggtgatgc 1680
ggttttggca gtacatcaat gggcgtggat agcggtttga ctcacgggga tttccaagtc 1740
tccaccccat tgacgtcaat gggagtttgt tttggcacca aaatcaacgg gactttccaa 1800
aatgtcgtaa caactccgcc ccattgacgc aaatgggcgg taggcgtgta cggtgggagg 1860
tctatataag cagagctggt ttagtgaacc gtcagatccg ctagggatcc tctagtcagc 1920
tgacgcgtgc tagcgcggcc gcatcgataa gcttgccacc atgcggattt ccaaacctca 1980
cctgcgatct atctccatcc agtgctatct gtgcctgctg ctgaactctc atttcctgac 2040
cgaagccggc atccacgtgt tcatcctggg ctgctttagc gccggcctgc caaagaccga 2100
ggcaaactgg gtgaatgtga tctctgacct gaagaagatc gaggatctga tccagagcat 2160
gcacatcgac gccaccctgt acacagagtc cgatgtgcac ccttcttgca aggtgacagc 2220
catgaagtgt ttcctgctgg agctgcaggt catctctctg gagagcggcg acgcctccat 2280
ccacgatacc gtggagaacc tgatcatcct ggccaacaat agcctgagct ccaacggcaa 2340
tgtgacagag tccggctgca aggagtgtga ggagctggag gagaagaaca tcaaggagtt 2400
cctgcagtct tttgtgcaca tcgtgcagat gtttatcaat accagcggag gaggaggatc 2460
cggcggagga ggctctggcg gcggcggcag ctgtggcggc aaggtgtccg ccctgaagga 2520
gaaggtgtct gccctgaagg aaaaagtgtc cgctctgaag gaaaaggtgt ccgcactgaa 2580
agaaaaggtc tccgccctga aggaataagt cga 2613
<210> 560
<211> 3135
<212> DNA
<213> 人工序列
<220>
<223> 合成序列
<400> 560
gagtaattca tacaaaagga ctcgcccctg ccttggggaa tcccagggac cgtcgttaaa 60
ctcccactaa cgtagaaccc agagatcgct gcgttcccgc cccctcaccc gcccgctctc 120
gtcatcactg aggtggagaa gagcatgcgt gaggctccgg tgcccgtcag tgggcagagc 180
gcacatcgcc cacagtcccc gagaagttgg ggggaggggt cggcaattga accggtgcct 240
agagaaggtg gcgcggggta aactgggaaa gtgatgtcgt gtactggctc cgcctttttc 300
ccgagggtgg gggagaaccg tatataagtg cagtagtcgc cgtgaacgtt ctttttcgca 360
acgggtttgc cgccagaaca caggtaagtg ccgtgtgtgg ttcccgcggg cctggcctct 420
ttacgggtta tggcccttgc gtgccttgaa ttacttccac gcccctggct gcagtacgtg 480
attcttgatc ccgagcttcg ggttggaagt gggtgggaga gttcgaggcc ttgcgcttaa 540
ggagcccctt cgcctcgtgc ttgagttgag gcctggcttg ggcgctgggg ccgccgcgtg 600
cgaatctggt ggcaccttcg cgcctgtctc gctgctttcg ataagtctct agccatttaa 660
aatttttgat gacctgctgc gacgcttttt ttctggcaag atagtcttgt aaatgcgggc 720
caagatctgc acactggtat ttcggttttt ggggccgcgg gcggcgacgg ggcccgtgcg 780
tcccagcgca catgttcggc gaggcggggc ctgcgagcgc ggccaccgag aatcggacgg 840
gggtagtctc aagctggccg gcctgctctg gtgcctggcc tcgcgccgcc gtgtatcgcc 900
ccgccctggg cggcaaggct ggcccggtcg gcaccagttg cgtgagcgga aagatggccg 960
cttcccggcc ctgctgcagg gagctcaaaa tggaggacgc ggcgctcggg agagcgggcg 1020
ggtgagtcac ccacacaaag gaaaagggcc tttccgtcct cagccgtcgc ttcatgtgac 1080
tccacggagt accgggcgcc gtccaggcac ctcgattagt tctcgagctt ttggagtacg 1140
tcgtctttag gttgggggga ggggttttat gcgatggagt ttccccacac tgagtgggtg 1200
gagactgaag ttaggccagc ttggcacttg atgtaattct ccttggaatt tgcccttttt 1260
gagtttggat cttggttcat tctcaagcct cagacagtgg ttcaaagttt ttttcttcca 1320
tttcaggtgt cgtgaactag aagctttatt gcggtagttt atcacagtta aattgctaac 1380
gcagtcagtg cttctgacac aacagtctcg aacttaagct gcagtgactc tcttaaggta 1440
gccttgcaga agttggtcgt gaggcactgg gcaggtaagt atcaaggtta caagacaggt 1500
ttaaggagac caatagaaac tgggcttgtc gagacagaga agactcttgc gtttctgata 1560
ggcacctatt ggtcttactg acatccactt tgcctttctc tccacaggtg tccactccca 1620
gttcaattac agctcttaag gctagagtac ttaatacgac tcactatagg ctagcgccac 1680
catgcggatt tccaagcccc atctgcgctc catttccatc cagtgttacc tgtgcctgct 1740
gctgaatagc cattttctga ccgaagccgg catccacgtg ttcatcctgg gctgcttttc 1800
cgccggcctg ccaaagaccg aggcaaactg ggtgaatgtg atctctgacc tgaagaagat 1860
cgaggatctg atccagagca tgcacatcga cgccaccctg tacacagagt ccgatgtgca 1920
cccttcttgc aaggtgacag ccatgaagtg tttcctgctg gagctgcagg tcatctctct 1980
ggagagcggc gacgcctcta tccacgatac cgtggagaac ctgatcatcc tggccaacaa 2040
tagcctgagc tccaacggca atgtgacaga gtccggctgc aaggagtgtg aggagctgga 2100
ggagaagaat atcaaagagt tcctgcagag tttcgtccat atcgtccaga tgtttatcaa 2160
tacttcctaa gaattcacgc gtcgagcatg catctagggc ggccaattcc gcccctctcc 2220
cccccccccc tctccctccc ccccccctaa cgttactggc cgaagccgct tggaataagg 2280
ccggtgtgcg tttgtctata tgttattttc caccatattg ccgtcttttg gcaatgtgag 2340
ggcccggaaa cctggccctg tcttcttgac gagcattcct aggggtcttt cccctctcgc 2400
caaaggaatg caaggtctgt tgaatgtcgt gaaggaagca gttcctctgg aagcttcttg 2460
aagacaaaca acgtctgtag cgaccctttg caggcagcgg aaccccccac ctggcgacag 2520
gtgcctctgc ggccaaaagc cacgtgtata agatacacct gcaaaggcgg cacaacccca 2580
gtgccacgtt gtgagttgga tagttgtgga aagagtcaaa tggctctcct caagcgtatt 2640
caacaagggg ctgaaggatg cccagaaggt accccattgt atgggatctg atctggggcc 2700
tcggtgcaca tgctttacat gtgtttagtc gaggttaaaa aaacgtctag gccccccgaa 2760
ccacggggac gtggttttcc tttgaaaaac acgatgataa gcttgccaca acccgggatc 2820
ctctagagtc gacgccacca tggctccacg ccgcgctaga ggatgtcgga ccctgggact 2880
gcctgccctg ctgctgctgc tgctgctgag accccccgct acaaggggca tcacctgccc 2940
acctccaatg agcgtggagc acgcagacat ctgggtgaag tcttacagcc tgtattcccg 3000
ggagagatac atctgcaact ctggcttcaa gcggaaggcc ggcaccagct ccctgacaga 3060
gtgcgtgctg aacaaggcaa caaatgtggc tcactggact accccatcac tgaaatgtat 3120
tagggattga gtcga 3135
<210> 561
<211> 3906
<212> DNA
<213> 人工序列
<220>
<223> 合成序列
<400> 561
gagtaattca tacaaaagga ctcgcccctg ccttggggaa tcccagggac cgtcgttaaa 60
ctcccactaa cgtagaaccc agagatcgct gcgttcccgc cccctcaccc gcccgctctc 120
gtcatcactg aggtggagaa gagcatgcgt gaggctccgg tgcccgtcag tgggcagagc 180
gcacatcgcc cacagtcccc gagaagttgg ggggaggggt cggcaattga accggtgcct 240
agagaaggtg gcgcggggta aactgggaaa gtgatgtcgt gtactggctc cgcctttttc 300
ccgagggtgg gggagaaccg tatataagtg cagtagtcgc cgtgaacgtt ctttttcgca 360
acgggtttgc cgccagaaca caggtaagtg ccgtgtgtgg ttcccgcggg cctggcctct 420
ttacgggtta tggcccttgc gtgccttgaa ttacttccac gcccctggct gcagtacgtg 480
attcttgatc ccgagcttcg ggttggaagt gggtgggaga gttcgaggcc ttgcgcttaa 540
ggagcccctt cgcctcgtgc ttgagttgag gcctggcttg ggcgctgggg ccgccgcgtg 600
cgaatctggt ggcaccttcg cgcctgtctc gctgctttcg ataagtctct agccatttaa 660
aatttttgat gacctgctgc gacgcttttt ttctggcaag atagtcttgt aaatgcgggc 720
caagatctgc acactggtat ttcggttttt ggggccgcgg gcggcgacgg ggcccgtgcg 780
tcccagcgca catgttcggc gaggcggggc ctgcgagcgc ggccaccgag aatcggacgg 840
gggtagtctc aagctggccg gcctgctctg gtgcctggcc tcgcgccgcc gtgtatcgcc 900
ccgccctggg cggcaaggct ggcccggtcg gcaccagttg cgtgagcgga aagatggccg 960
cttcccggcc ctgctgcagg gagctcaaaa tggaggacgc ggcgctcggg agagcgggcg 1020
ggtgagtcac ccacacaaag gaaaagggcc tttccgtcct cagccgtcgc ttcatgtgac 1080
tccacggagt accgggcgcc gtccaggcac ctcgattagt tctcgagctt ttggagtacg 1140
tcgtctttag gttgggggga ggggttttat gcgatggagt ttccccacac tgagtgggtg 1200
gagactgaag ttaggccagc ttggcacttg atgtaattct ccttggaatt tgcccttttt 1260
gagtttggat cttggttcat tctcaagcct cagacagtgg ttcaaagttt ttttcttcca 1320
tttcaggtgt cgtgaactag aagctttatt gcggtagttt atcacagtta aattgctaac 1380
gcagtcagtg cttctgacac aacagtctcg aacttaagct gcagtgactc tcttaaggta 1440
gccttgcaga agttggtcgt gaggcactgg gcaggtaagt atcaaggtta caagacaggt 1500
ttaaggagac caatagaaac tgggcttgtc gagacagaga agactcttgc gtttctgata 1560
ggcacctatt ggtcttactg acatccactt tgcctttctc tccacaggtg tccactccca 1620
gttcaattac agctcttaag gctagagtac ttaatacgac tcactatagg ctagcgccac 1680
catgcggatt tccaagcccc atctgcgctc catttccatc cagtgttacc tgtgcctgct 1740
gctgaatagc cattttctga ccgaagccgg catccacgtg ttcatcctgg gctgcttttc 1800
cgccggcctg ccaaagaccg aggcaaactg ggtgaatgtg atctctgacc tgaagaagat 1860
cgaggatctg atccagagca tgcacatcga cgccaccctg tacacagagt ccgatgtgca 1920
cccttcttgc aaggtgacag ccatgaagtg tttcctgctg gagctgcagg tcatctctct 1980
ggagagcggc gacgcctcta tccacgatac cgtggagaac ctgatcatcc tggccaacaa 2040
tagcctgagc tccaacggca atgtgacaga gtccggctgc aaggagtgtg aggagctgga 2100
ggagaagaat atcaaagagt tcctgcagag tttcgtccat atcgtccaga tgtttatcaa 2160
tacttcctaa gaattcacgc gtcgagcatg catctagggc ggccaattcc gcccctctcc 2220
cccccccccc tctccctccc ccccccctaa cgttactggc cgaagccgct tggaataagg 2280
ccggtgtgcg tttgtctata tgttattttc caccatattg ccgtcttttg gcaatgtgag 2340
ggcccggaaa cctggccctg tcttcttgac gagcattcct aggggtcttt cccctctcgc 2400
caaaggaatg caaggtctgt tgaatgtcgt gaaggaagca gttcctctgg aagcttcttg 2460
aagacaaaca acgtctgtag cgaccctttg caggcagcgg aaccccccac ctggcgacag 2520
gtgcctctgc ggccaaaagc cacgtgtata agatacacct gcaaaggcgg cacaacccca 2580
gtgccacgtt gtgagttgga tagttgtgga aagagtcaaa tggctctcct caagcgtatt 2640
caacaagggg ctgaaggatg cccagaaggt accccattgt atgggatctg atctggggcc 2700
tcggtgcaca tgctttacat gtgtttagtc gaggttaaaa aaacgtctag gccccccgaa 2760
ccacggggac gtggttttcc tttgaaaaac acgatgataa gcttgccaca acccgggatc 2820
ctctagagtc gacgccacca tgagactggc aggaagacag gtccccgaac agagatcccc 2880
tccaccaccc ggactgggca gcgcaagacc cggctcaccc gccgtgtcct gcggagcagc 2940
agcaatggca ccaaggagag ccaggggctg tcgcaccctg ggcctgcccg ccctgttatt 3000
actgctgctg ctgaggcccc ctgcaacacg cgacgcaagg gatcgcctgg ccgtgctggc 3060
aggccggagc agaatctccg agtctttcaa ccacgaggtg cagacccacg aggcatgcgt 3120
gaggctgagg acaatggaga attgccccca gtgtcaccac caccggacca gcagacagca 3180
ggcaggcatc acatgtccac cccctatgtc cgtggagcac gccgacatct gggtgaagag 3240
ctactccctg tattctcggg agagatacat ctgcaacagc ggctttaaga ggaaggccgg 3300
caccagctcc ctgacagagt gcgtgctgaa caaggccacc aatgtggccc actggaccac 3360
accctctctg aagtgcatcc gggatcccgc cctggtgcac cagcggcccg caccacccag 3420
caccgtgacc acagccggcg tgacaccaca gccagagtct ctgagcccat ccggcaagga 3480
gcctgcagca tctagcccat cctctaacaa taccgcagca accacagcag caatcgtgcc 3540
tggctcccag ctgatgcctt ctaagagccc atccacaggc accacagaga tcagctccca 3600
cgagtctagc cacggcaccc cttctcagac cacagccaag aattgggagc tgacagcatc 3660
tgccagccac cagcctccag gcgtgtaccc acagggccac tccgacacca cagtggccat 3720
ctccacctct acagtgctgc tgtgcggcct gagcgccgtg tccctgctgg cctgttatct 3780
gaagtccaga cagacccccc ctctggcctc tgtggagatg gaggccatgg aggccctgcc 3840
cgtcacctgg ggaacttcat caagagacga ggacctggaa aactgtagtc accatctgta 3900
agtcga 3906
<210> 562
<211> 3487
<212> DNA
<213> 人工序列
<220>
<223> 合成序列
<400> 562
gagtaattca tacaaaagga ctcgcccctg ccttggggaa tcccagggac cgtcgttaaa 60
ctcccactaa cgtagaaccc agagatcgct gcgttcccgc cccctcaccc gcccgctctc 120
gtcatcactg aggtggagaa gagcatgcgt gaggctccgg tgcccgtcag tgggcagagc 180
gcacatcgcc cacagtcccc gagaagttgg ggggaggggt cggcaattga accggtgcct 240
agagaaggtg gcgcggggta aactgggaaa gtgatgtcgt gtactggctc cgcctttttc 300
ccgagggtgg gggagaaccg tatataagtg cagtagtcgc cgtgaacgtt ctttttcgca 360
acgggtttgc cgccagaaca caggtaagtg ccgtgtgtgg ttcccgcggg cctggcctct 420
ttacgggtta tggcccttgc gtgccttgaa ttacttccac gcccctggct gcagtacgtg 480
attcttgatc ccgagcttcg ggttggaagt gggtgggaga gttcgaggcc ttgcgcttaa 540
ggagcccctt cgcctcgtgc ttgagttgag gcctggcttg ggcgctgggg ccgccgcgtg 600
cgaatctggt ggcaccttcg cgcctgtctc gctgctttcg ataagtctct agccatttaa 660
aatttttgat gacctgctgc gacgcttttt ttctggcaag atagtcttgt aaatgcgggc 720
caagatctgc acactggtat ttcggttttt ggggccgcgg gcggcgacgg ggcccgtgcg 780
tcccagcgca catgttcggc gaggcggggc ctgcgagcgc ggccaccgag aatcggacgg 840
gggtagtctc aagctggccg gcctgctctg gtgcctggcc tcgcgccgcc gtgtatcgcc 900
ccgccctggg cggcaaggct ggcccggtcg gcaccagttg cgtgagcgga aagatggccg 960
cttcccggcc ctgctgcagg gagctcaaaa tggaggacgc ggcgctcggg agagcgggcg 1020
ggtgagtcac ccacacaaag gaaaagggcc tttccgtcct cagccgtcgc ttcatgtgac 1080
tccacggagt accgggcgcc gtccaggcac ctcgattagt tctcgagctt ttggagtacg 1140
tcgtctttag gttgggggga ggggttttat gcgatggagt ttccccacac tgagtgggtg 1200
gagactgaag ttaggccagc ttggcacttg atgtaattct ccttggaatt tgcccttttt 1260
gagtttggat cttggttcat tctcaagcct cagacagtgg ttcaaagttt ttttcttcca 1320
tttcaggtgt cgtgaactag aagctttatt gcggtagttt atcacagtta aattgctaac 1380
gcagtcagtg cttctgacac aacagtctcg aacttaagct gcagtgactc tcttaaggta 1440
gccttgcaga agttggtcgt gaggcactgg gcaggtaagt atcaaggtta caagacaggt 1500
ttaaggagac caatagaaac tgggcttgtc gagacagaga agactcttgc gtttctgata 1560
ggcacctatt ggtcttactg acatccactt tgcctttctc tccacaggtg tccactccca 1620
gttcaattac agctcttaag gctagagtac ttaatacgac tcactatagg ctagcgccac 1680
catgcggatt tccaaacctc acctgcgatc tatctccatc cagtgctatc tgtgcctgct 1740
gctgaactct catttcctga ccgaagccgg catccacgtg ttcatcctgg gctgctttag 1800
cgccggcctg ccaaagaccg aggcaaactg ggtgaatgtg atctctgacc tgaagaagat 1860
cgaggatctg atccagagca tgcacatcga cgccaccctg tacacagagt ccgatgtgca 1920
cccttcttgc aaggtgacag ccatgaagtg tttcctgctg gagctgcagg tcatctctct 1980
ggagagcggc gacgcctcca tccacgatac cgtggagaac ctgatcatcc tggccaacaa 2040
tagcctgagc tccaacggca atgtgacaga gtccggctgc aaggagtgtg aggagctgga 2100
ggagaagaac atcaaggagt tcctgcagtc ttttgtgcac atcgtgcaga tgtttatcaa 2160
taccagcgga ggaggaggat ccggcggagg aggctctggc ggcggcggca gctgtggcgg 2220
caaggtgtcc gccctgaagg agaaggtgtc tgccctgaag gaaaaagtgt ccgctctgaa 2280
ggaaaaggtg tccgcactga aagaaaaggt ctccgccctg aaggaataag aattcacgcg 2340
tcgagcatgc atctagggcg gccaattccg cccctctccc ccccccccct ctccctcccc 2400
cccccctaac gttactggcc gaagccgctt ggaataaggc cggtgtgcgt ttgtctatat 2460
gttattttcc accatattgc cgtcttttgg caatgtgagg gcccggaaac ctggccctgt 2520
cttcttgacg agcattccta ggggtctttc ccctctcgcc aaaggaatgc aaggtctgtt 2580
gaatgtcgtg aaggaagcag ttcctctgga agcttcttga agacaaacaa cgtctgtagc 2640
gaccctttgc aggcagcgga accccccacc tggcgacagg tgcctctgcg gccaaaagcc 2700
acgtgtataa gatacacctg caaaggcggc acaaccccag tgccacgttg tgagttggat 2760
agttgtggaa agagtcaaat ggctctcctc aagcgtattc aacaaggggc tgaaggatgc 2820
ccagaaggta ccccattgta tgggatctga tctggggcct cggtgcacat gctttacatg 2880
tgtttagtcg aggttaaaaa aacgtctagg ccccccgaac cacggggacg tggttttcct 2940
ttgaaaaaca cgatgataag cttgccacaa cccgggatcc tctagagtcg acgccaccat 3000
ggcccctaga agagcccgag gatgtcgcac actgggactg cctgccctgc tgctgctgct 3060
gctgctgaga ccacctgcta caaggggcat cacctgccca cctccaatga gcgtggagca 3120
cgcagacatc tgggtgaagt cttacagcct gtattctcgg gagagataca tctgcaacag 3180
cggcttcaag aggaaggccg gcaccagctc cctgacagag tgcgtgctga acaaggccac 3240
aaatgtggcc cactggacca caccctccct gaagtgtatc cgggatggag gaggaggaag 3300
cggaggagga ggatccggcg gcggcggctc cgaggtgtct gccctggaga aggaggtgtc 3360
tgccctggaa aaagaagtct cagccctgga aaaggaggtg tcagccctgg aaaaagaggt 3420
gtccgcactg gaaaaataag tcgaagtcgg gacctttttc tccacaggcg tgaccttttt 3480
attcagc 3487
<210> 563
<211> 4215
<212> DNA
<213> 人工序列
<220>
<223> 合成序列
<400> 563
gagtaattca tacaaaagga ctcgcccctg ccttggggaa tcccagggac cgtcgttaaa 60
ctcccactaa cgtagaaccc agagatcgct gcgttcccgc cccctcaccc gcccgctctc 120
gtcatcactg aggtggagaa gagcatgcgt gaggctccgg tgcccgtcag tgggcagagc 180
gcacatcgcc cacagtcccc gagaagttgg ggggaggggt cggcaattga accggtgcct 240
agagaaggtg gcgcggggta aactgggaaa gtgatgtcgt gtactggctc cgcctttttc 300
ccgagggtgg gggagaaccg tatataagtg cagtagtcgc cgtgaacgtt ctttttcgca 360
acgggtttgc cgccagaaca caggtaagtg ccgtgtgtgg ttcccgcggg cctggcctct 420
ttacgggtta tggcccttgc gtgccttgaa ttacttccac gcccctggct gcagtacgtg 480
attcttgatc ccgagcttcg ggttggaagt gggtgggaga gttcgaggcc ttgcgcttaa 540
ggagcccctt cgcctcgtgc ttgagttgag gcctggcttg ggcgctgggg ccgccgcgtg 600
cgaatctggt ggcaccttcg cgcctgtctc gctgctttcg ataagtctct agccatttaa 660
aatttttgat gacctgctgc gacgcttttt ttctggcaag atagtcttgt aaatgcgggc 720
caagatctgc acactggtat ttcggttttt ggggccgcgg gcggcgacgg ggcccgtgcg 780
tcccagcgca catgttcggc gaggcggggc ctgcgagcgc ggccaccgag aatcggacgg 840
gggtagtctc aagctggccg gcctgctctg gtgcctggcc tcgcgccgcc gtgtatcgcc 900
ccgccctggg cggcaaggct ggcccggtcg gcaccagttg cgtgagcgga aagatggccg 960
cttcccggcc ctgctgcagg gagctcaaaa tggaggacgc ggcgctcggg agagcgggcg 1020
ggtgagtcac ccacacaaag gaaaagggcc tttccgtcct cagccgtcgc ttcatgtgac 1080
tccacggagt accgggcgcc gtccaggcac ctcgattagt tctcgagctt ttggagtacg 1140
tcgtctttag gttgggggga ggggttttat gcgatggagt ttccccacac tgagtgggtg 1200
gagactgaag ttaggccagc ttggcacttg atgtaattct ccttggaatt tgcccttttt 1260
gagtttggat cttggttcat tctcaagcct cagacagtgg ttcaaagttt ttttcttcca 1320
tttcaggtgt cgtgaactag aagctttatt gcggtagttt atcacagtta aattgctaac 1380
gcagtcagtg cttctgacac aacagtctcg aacttaagct gcagtgactc tcttaaggta 1440
gccttgcaga agttggtcgt gaggcactgg gcaggtaagt atcaaggtta caagacaggt 1500
ttaaggagac caatagaaac tgggcttgtc gagacagaga agactcttgc gtttctgata 1560
ggcacctatt ggtcttactg acatccactt tgcctttctc tccacaggtg tccactccca 1620
gttcaattac agctcttaag gctagagtac ttaatacgac tcactatagg ctagcgccac 1680
catgcggatt tccaaacctc acctgcgatc tatctccatc cagtgctatc tgtgcctgct 1740
gctgaactct catttcctga ccgaagccgg catccacgtg ttcatcctgg gctgctttag 1800
cgccggcctg ccaaagaccg aggcaaactg ggtgaatgtg atctctgacc tgaagaagat 1860
cgaggatctg atccagagca tgcacatcga cgccaccctg tacacagagt ccgatgtgca 1920
cccttcttgc aaggtgacag ccatgaagtg tttcctgctg gagctgcagg tcatctctct 1980
ggagagcggc gacgcctcca tccacgatac cgtggagaac ctgatcatcc tggccaacaa 2040
tagcctgagc tccaacggca atgtgacaga gtccggctgc aaggagtgtg aggagctgga 2100
ggagaagaac atcaaggagt tcctgcagtc ttttgtgcac atcgtgcaga tgtttatcaa 2160
taccagcgga ggaggaggat ccggcggagg aggctctggc ggcggcggca gctgtggcgg 2220
caaggtgtcc gccctgaagg agaaggtgtc tgccctgaag gaaaaagtgt ccgctctgaa 2280
ggaaaaggtg tccgcactga aagaaaaggt ctccgccctg aaggaataag aattcacgcg 2340
tcgagcatgc atctagggcg gccaattccg cccctctccc ccccccccct ctccctcccc 2400
cccccctaac gttactggcc gaagccgctt ggaataaggc cggtgtgcgt ttgtctatat 2460
gttattttcc accatattgc cgtcttttgg caatgtgagg gcccggaaac ctggccctgt 2520
cttcttgacg agcattccta ggggtctttc ccctctcgcc aaaggaatgc aaggtctgtt 2580
gaatgtcgtg aaggaagcag ttcctctgga agcttcttga agacaaacaa cgtctgtagc 2640
gaccctttgc aggcagcgga accccccacc tggcgacagg tgcctctgcg gccaaaagcc 2700
acgtgtataa gatacacctg caaaggcggc acaaccccag tgccacgttg tgagttggat 2760
agttgtggaa agagtcaaat ggctctcctc aagcgtattc aacaaggggc tgaaggatgc 2820
ccagaaggta ccccattgta tgggatctga tctggggcct cggtgcacat gctttacatg 2880
tgtttagtcg aggttaaaaa aacgtctagg ccccccgaac cacggggacg tggttttcct 2940
ttgaaaaaca cgatgataag cttgccacaa cccgggatcc tctagagtcg acgccaccat 3000
gcggctggct ggaaggcagg tccccgagca gagatcccct cctcctcctg ggctgggcag 3060
tgcaagaccc ggcagtcccg ctgtgtcctg cggagcagca gcaatggcac caaggagagc 3120
caggggctgt cgcaccctgg gcctgcccgc cctgttatta ctgctgctgc tgaggccccc 3180
tgcaacacgc gacgcaaggg atcgcctggc cgtgctggca ggccggagca gaatcagcga 3240
gtccttcaac cacgaggtgc agacccacga ggcatgcgtg aggctgagga caatggagaa 3300
ttgcccccag tgtcaccacc accggaccag cagacagcag gcaggcatca catgtccacc 3360
ccctatgtcc gtggagcacg ccgacatctg ggtgaagtct tacagcctgt attctcggga 3420
gagatacatc tgcaacagcg gctttaagcg gaaggccggc accagctccc tgacagagtg 3480
cgtgctgaac aaggccacca atgtggccca ctggaccaca ccctctctga agtgcatccg 3540
ggatcccgcc ctggtgcacc agcggcccgc accacccagc accgtgacca cagcaggagt 3600
gacaccacag ccagagtccc tgtctccaag cggcaaggag cctgcagcat ctagcccatc 3660
ctctaacaat accgcagcaa ccacagcagc aatcgtgcct ggctcccagc tgatgccttc 3720
caagtctcca agcaccggca ccacagagat cagctcccac gagtctagcc acggcacccc 3780
ttctcagacc acagccaaga actgggagct gacagcatcc gcctctcacc agcctccagg 3840
cgtgtaccca cagggccact ccgacaccac agtggccatc agcacctcca cagtgctgct 3900
gtgcggcctg tctgccgtga gcctgctggc ctgttatctg aagtccaggc agaccccacc 3960
tctggcatct gtggagatgg aggcaatgga ggccctgcca gtgacctggg gcacatcctc 4020
tcgcgacgag gatctggaga attgttccca ccacctggga ggaggaggaa gcggaggagg 4080
aggctccggc ggcggcggct ccgaggtgtc tgccctggaa aaagaggtga gcgccctgga 4140
aaaagaagtg tcagccctgg agaaggaggt gtcagcactg gaaaaagagg tgtccgcact 4200
ggaaaaataa gtcga 4215
<210> 564
<211> 3425
<212> DNA
<213> 人工序列
<220>
<223> 合成序列
<400> 564
acattgatta ttgactagtt attaatagta atcaattacg gggtcattag ttcatagccc 60
atatatggag ttccgcgtta cataacttac ggtaaatggc ccgcctggct gaccgcccaa 120
cgacccccgc ccattgacgt caataatgac gtatgttccc atagtaacgc caatagggac 180
tttccattga cgtcaatggg tggagtattt acggtaaact gcccacttgg cagtacatca 240
agtgtatcat atgccaagta cgccccctat tgacgtcaat gacggtaaat ggcccgcctg 300
gcattatgcc cagtacatga ccttatggga ctttcctact tggcagtaca tctacgtatt 360
agtcatcgct attaccatgg tgatgcggtt ttggcagtac atcaatgggc gtggatagcg 420
gtttgactca cggggatttc caagtctcca ccccattgac gtcaatggga gtttgttttg 480
gcaccaaaat caacgggact ttccaaaatg tcgtaacaac tccgccccat tgacgcaaat 540
gggcggtagg cgtgtacggt gggaggtcta tataagcaga gctctctggc taactagaga 600
acccactgct tactggctta tcgaaattaa tacgactcac tatagggaga cccaagctgg 660
ctagcgttta aacttaagct tggtaccgag ctcggatcca ctagtccagt gtggtggaat 720
tcgccaccat gtgccctcag aaactgacta tctcatggtt cgcaatcgtg ctgctggtct 780
cacccctgat ggctatgtgg gaactggaaa aggatgtgta cgtggtggag gtggactgga 840
cacccgatgc ccctggcgag acagtgaacc tgacatgcga cacccccgag gaggacgaca 900
tcacctggac atccgatcag cggcacggcg tgatcggctc tggcaagacc ctgacaatca 960
ccgtgaagga gttcctggac gccggccagt acacatgtca caagggcggc gagacactga 1020
gccactccca cctgctgctg cacaagaagg agaacggcat ctggtccaca gagatcctga 1080
agaacttcaa gaataagacc tttctgaagt gcgaggcccc caattattct ggccggttca 1140
cctgtagctg gctggtgcag agaaacatgg acctgaagtt taatatcaag agctcctcta 1200
gctcccctga tagcagggca gtgacatgcg gaatggcatc tctgagcgcc gagaaggtga 1260
ccctggacca gagagattac gagaagtatt ccgtgtcttg ccaggaggat gtgacatgtc 1320
ccaccgccga ggagacactg cctatcgagc tggccctgga ggcaaggcag cagaacaagt 1380
acgagaatta tagcacctcc ttctttatca gagacatcat caagccagat ccccctaaga 1440
acctgcagat gaagcccctg aagaacagcc aggtcgaggt gagctgggag taccctgact 1500
cttggagcac accacactct tatttcagcc tgaagttctt tgtgaggatc cagcgcaaga 1560
aggagaagat gaaggagaca gaggagggct gcaaccagaa gggcgccttt ctggtggaga 1620
agacatccac cgaggtgcag tgcaagggag gaaacgtgtg cgtgcaggca caggatagat 1680
actataattc tagctgctct aagtgggcct gcgtgccctg tagggtgcgc tccggaggcg 1740
gcggctctgg aggaggagga agcggaggag gaggaagcat gtgccagtcc aggtacctgc 1800
tgttcctggc caccctggcc ctgctgaacc acctgtccct ggcacgcgtg atcccagtgt 1860
ctggaccagc ccggtgcctg tcccagtcta gaaatctgct gaagaccaca gacgatatgg 1920
tgaagacagc cagggagaag ctgaagcact attcctgtac cgccgaggac atcgatcacg 1980
aggacatcac acgcgatcag acatccaccc tgaagacctg cctgcctctg gagctgcaca 2040
agaacgagtc ttgtctggcc acacgggaga caagctctac cacaagaggc agctgcctgc 2100
caccccagaa gacatccctg atgatgaccc tgtgcctggg cagcatctac gaggacctga 2160
agatgtatca gacagagttt caggccatca atgccgccct gcagaaccac aatcaccagc 2220
agatcatcct ggacaagggc atgctggtgg ccatcgatga gctgatgcag tccctgaacc 2280
acaatggcga gacactgagg cagaagcctc cagtgggcga ggccgatcct taccgcgtga 2340
agatgaagct gtgcatcctg ctgcacgcct tcagcacaag ggtggtgacc atcaaccgcg 2400
tgatgggcta tctgagctcc gccggaggag gaggatccgg cggaggaggc tctggcggcg 2460
gcggcagcgg ctccggcgcc accaactttt ctctgctgaa gcaggcaggc gacgtggagg 2520
agaatccagg acccatgagg atcagcaagc cacacctgcg ctctatcagc atccagtgct 2580
acctgtgcct gctgctgaat agccacttcc tgacagaggc cggcatccac gtgttcatcc 2640
tgggctgttt ttccgccggc ctgccaaaga ccgaggccaa ctgggtgaat gtgatctctg 2700
acctgaagaa gatcgaggat ctgatccaga gcatgcacat cgacgccaca ctgtataccg 2760
agagcgatgt gcacccctcc tgcaaggtga ccgccatgaa gtgttttctg ctggagctgc 2820
aggtcatcag cctggagtct ggcgacgcca gcatccacga tacagtggag aacctgatca 2880
tcctggccaa caatagcctg tctagcaacg gcaatgtgac cgagtccggc tgcaaggagt 2940
gtgaggagct ggaggagaag aacatcaagg agttcctgca gtcctttgtg cacatcgtgc 3000
agatgttcat caatacatcc ggcggcggcg gctccggcgg cggagggagc ggaggaggcg 3060
gctccggctc tggcgccacc aactttagcc tgctgaagca ggccggcgac gtggaagaaa 3120
atcctggacc aatggcacct aggagagcaa ggggatgcag aaccctgggc ctgccagccc 3180
tgttattact gctgctgctg aggccccctg caacaagggg aatcacctgt ccacccccta 3240
tgagcgtgga gcacgccgac atctgggtga agagctactc cctgtattct cgggagagat 3300
acatctgcaa tagcggcttc aagcggaagg ccggcacatc ctctctgacc gagtgcgtgc 3360
tgaacaaagc aacaaacgtg gctcattgga caacaccatc cctgaagtgc atccgcgact 3420
aagat 3425
<210> 565
<211> 3912
<212> DNA
<213> 人工序列
<220>
<223> 合成序列
<400> 565
acattgatta ttgactagtt attaatagta atcaattacg gggtcattag ttcatagccc 60
atatatggag ttccccgcct ggctgaccgc ccaacgaccc ccgcccattg acgtcaataa 120
tgacgtatgt tcccatagta acgccaatag ggactttcca ttgacgtcaa tgggtggagt 180
atttacggta aactgcccac ttggcagtac atcaagtgta tcatatgcca agtacgcccc 240
ctattgacgt caatgacggt aaatggcccg cctggcatta tgcccagtac atgaccttat 300
gggactttcc tacttggcag tacatctacg tattagtcat cgctattacc atggtgatgc 360
ggttttggca gtacatcaat gggcgtggat agcggtttga ctcacgggga tttccaagtc 420
tccaccccat tgacgtcaat gggagtttgt tttggcacca aaatcaacgg gactttccaa 480
aatgtcgtaa caactccgcc ccattgacgc aaatgggcgg taggcgtgta cggtgggagg 540
tctatataag cagagctctc tggctaacta gagaacccac tgcttactgg cttatcgaaa 600
ttaatacgac tcactatagg gagacccaag ctggctagcg tttaaactta agcttggtac 660
cgagctcgga tccactagtc cagtgtggtg gaattcgcca ccatgtgccc tcagaagctg 720
actatctctt ggtttgctat tgtgctgctg gtctcacccc tgatggctat gtgggaactg 780
gaaaaggatg tgtacgtggt ggaggtggac tggacaccag atgcccccgg cgagacagtg 840
aacctgacat gcgacacccc cgaggaggac gacatcacct ggacatctga tcagaggcac 900
ggcgtgatcg gaagcggcaa gaccctgaca atcaccgtga aggagttcct ggacgccggc 960
cagtacacat gtcacaaggg cggcgagaca ctgtctcaca gccacctgct gctgcacaag 1020
aaggagaacg gcatctggag cacagagatc ctgaagaact tcaagaataa gacctttctg 1080
aagtgcgagg ccccaaatta ttccggcagg ttcacctgtt cttggctggt gcagcgcaac 1140
atggacctga agtttaatat caagagctcc tctagctccc ccgattccag ggcagtgaca 1200
tgcggaatgg catccctgtc tgccgagaag gtgaccctgg accagcgcga ttacgagaag 1260
tatagcgtgt cctgccagga ggatgtgaca tgtcctaccg ccgaggagac actgccaatc 1320
gagctggccc tggaggccag gcagcagaac aagtacgaga attattctac cagcttcttt 1380
atccgcgaca tcatcaagcc agatccccct aagaacctgc agatgaagcc cctgaagaac 1440
agccaggtcg aggtgtcttg ggagtaccca gactcctggt ctacacccca ctcttatttc 1500
agcctgaagt tctttgtgag gatccagcgc aagaaggaga agatgaagga gacagaggag 1560
ggctgcaacc agaagggcgc ctttctggtg gagaagacat ccaccgaggt gcagtgcaag 1620
ggaggaaacg tgtgcgtgca ggcacaggat agatactata attctagctg cagcaagtgg 1680
gcctgcgtgc cttgtagggt gcgcagcgga ggaggaggat ccggaggagg cggctctgga 1740
ggaggaggat ctatgtgcca gagccggtac ctgctgttcc tggccaccct ggccctgctg 1800
aaccacctga gcctggcaag agtgatcccc gtgagcggac cagcaaggtg cctgagccag 1860
tccagaaatc tgctgaagac cacagacgat atggtgaaga cagcccggga gaagctgaag 1920
cactatagct gtaccgccga ggacatcgat cacgaggaca tcacaagaga tcagacatct 1980
accctgaaga cctgcctgcc cctggagctg cacaagaacg agagctgtct ggccacacgg 2040
gagacaagct ctaccacaag aggctcttgc ctgccacccc agaagacaag cctgatgatg 2100
accctgtgcc tgggcagcat ctacgaggac ctgaagatgt atcagaccga gtttcaggcc 2160
atcaatgccg ccctgcagaa ccacaatcac cagcagatca tcctggacaa gggcatgctg 2220
gtggccatcg atgagctgat gcagagcctg aaccacaatg gcgagacact gaggcagaag 2280
cctccagtgg gagaggcaga tccatacaga gtgaagatga agctgtgcat cctgctgcac 2340
gccttctcca caagggtggt gaccatcaac cgcgtgatgg gctatctgag ctccgccgga 2400
ggaggaggaa gcggcggagg aggcagcggc ggcggcggct ctggcagcgg cgccaccaac 2460
tttagcctgc tgaagcaggc aggcgacgtg gaggagaatc caggacccat gaggatctcc 2520
aagccccacc tgcgctccat ctctatccag tgctacctgt gcctgctgct gaacagccac 2580
ttcctgacag aggccggcat ccacgtgttc atcctgggct gtttttctgc cggcctgcct 2640
aagaccgagg ccaactgggt gaatgtgatc agcgacctga agaagatcga ggatctgatc 2700
cagtccatgc acatcgacgc cacactgtat accgagtctg atgtgcaccc aagctgcaag 2760
gtgaccgcca tgaagtgttt tctgctggag ctgcaggtca tcagcctgga gtctggcgac 2820
gccagcatcc acgatacagt ggagaacctg atcatcctgg ccaacaattc cctgtctagc 2880
aacggcaatg tgaccgagtc tggctgcaag gagtgtgagg agctggagga gaagaacatc 2940
aaggagttcc tgcagagctt tgtgcacatc gtgcagatgt tcatcaatac aagcggaggc 3000
ggaggatctg gcggcggcgg cagtggcgga ggaggaagcg gctccggcgc caccaacttt 3060
tccctgctga agcaggccgg cgacgtggaa gaaaatcctg gaccaatggc acctaggaga 3120
gcaaggggat gcagaaccct gggcctgcca gccctgttat tactgctgct gctgaggccc 3180
cctgcaacaa ggggaatcac ctgtccaccc cctatgagcg tggagcacgc cgacatctgg 3240
gtgaagtctt acagcctgta ttcccgggag agatacatct gcaactctgg cttcaagagg 3300
aaggccggca catcctctct gaccgagtgc gtgctgaaca aggccaccaa tgtggcccac 3360
tggaccacac cctctctgaa gtgcatccgg gaccccgccc tggtgcacca gcggcccgca 3420
ccacccagca cagtgaccac agcaggagtg accccacagc ctgagtccct gtctccaagc 3480
ggcaaggagc cagcagcaag ctccccttct agcaacaata cagcagcaac cacagcagca 3540
atcgtgcctg gctcccagct gatgccctcc aagtctccta gcaccggcac cacagagatc 3600
tcctctcacg agagctccca cggcacaccc agccagacca cagccaagaa ttgggagctg 3660
accgcatccg cctctcacca gcctccaggc gtgtaccctc agggccactc cgataccaca 3720
gtggccatca gcacatccac cgtgctgctg tgcggcctga gcgccgtgtc cctgctggcc 3780
tgttatctga agagcaggca gaccccacct ctggcatccg tggagatgga ggccatggag 3840
gccctgcccg tcacctgggg gacatcatca cgggacgaag acctggagaa ctgctcacat 3900
catctgtaag at 3912
<210> 566
<211> 3808
<212> DNA
<213> 人工序列
<220>
<223> 合成序列
<400> 566
acattgatta ttgactagtt attaatagta atcaattacg gggtcattag ttcatagccc 60
atatatggag ttccgcgtta cataacttac ggtaaatggc tgtaactaat aactgatcaa 120
taattatcat tagttaatgc cccagtaatc aagtatcggg tatatacctc aaggccgcct 180
ggctgaccgc ccaacgaccc ccgcccattg acgtcaataa tgacgtatgt tcccatagta 240
acgccaatag ggactttcca ttgacgtcaa tgggtggagt atttacggta aactgcccac 300
ttggcagtac atcaagtgta tcatatgcca agtacgcccc ctattgacgt caatgacggt 360
aaatggcccg cctggcatta tgcccagtac atgaccttat gggactttcc tacttggcag 420
tacatctacg tattagtcat cgctattacc atggtgatgc ggttttggca gtacatcaat 480
gggcgtggat agcggtttga ctcacgggga tttccaagtc tccaccccat tgacgtcaat 540
gggagtttgt tttggcacca aaatcaacgg gactttccaa aatgtcgtaa caactccgcc 600
ccattgacgc aaatgggcgg taggcgtgta cggtgggagg tctatataag cagagctctc 660
tggctaacta gagaacccac tgcttactgg cttatcgaaa ttaatacgac tcactatagg 720
gagacccaag ctggctagcg tttaaactta agcttggtac cgagctcgga tccactagtc 780
cagtgtggtg gaattcgcca ccatgtgccc tcagaaactg acaatctcct ggttcgctat 840
cgtcctgctg gtctctcctc tgatggctat gtgggaactg gaaaaagatg tgtacgtggt 900
ggaggtggac tggacacccg atgcccctgg cgagacagtg aacctgacat gcgacacccc 960
cgaggaggac gacatcacct ggacatccga tcagaggcac ggcgtgatcg gctctggcaa 1020
gaccctgaca atcaccgtga aggagttcct ggacgccggc cagtacacat gtcacaaggg 1080
cggcgagaca ctgagccact cccacctgct gctgcacaag aaggagaacg gcatctggtc 1140
cacagagatc ctgaagaact tcaagaataa gacctttctg aagtgcgagg cccccaatta 1200
tagcggccgg ttcacctgtt cctggctggt gcagagaaac atggacctga agtttaatat 1260
caagagctcc tctagctccc ctgatagcag ggcagtgaca tgcggaatgg catctctgag 1320
cgccgagaag gtgaccctgg accagagaga ttacgagaag tattccgtgt cttgccagga 1380
ggatgtgaca tgtcccaccg ccgaggagac actgcctatc gagctggccc tggaggcaag 1440
gcagcagaac aagtacgaga attatagcac ctccttcttt atcagagaca tcatcaagcc 1500
agatccccct aagaacctgc agatgaagcc cctgaagaac agccaggtcg aggtgtcttg 1560
ggagtaccct gactcttgga gcacaccaca ctcttatttc agcctgaagt tctttgtgag 1620
gatccagcgc aagaaggaga agatgaagga gacagaggag ggctgtaacc agaagggcgc 1680
ctttctggtg gagaagacat ccaccgaggt gcagtgcaag ggaggaaacg tgtgcgtgca 1740
ggcacaggat cggtactata attctagctg ctctaagtgg gcctgcgtgc cctgtagggt 1800
gcgcagcgga ggaggaggat ccggaggagg cggctctgga ggaggaggat ctatgtgcca 1860
gagcaggtac ctgctgttcc tggccaccct ggccctgctg aaccacctgt ccctggcacg 1920
cgtgatccca gtgtctggac cagcccggtg cctgtcccag tctagaaatc tgctgaagac 1980
cacagacgat atggtgaaga cagccaggga gaagctgaag cactatagct gtaccgccga 2040
ggacatcgat cacgaggaca tcacacgcga tcagacatcc accctgaaga cctgcctgcc 2100
tctggagctg cacaagaacg agtcttgtct ggccacacgg gagacaagct ctaccacaag 2160
aggcagctgc ctgccacccc agaagacatc cctgatgatg accctgtgcc tgggcagcat 2220
ctacgaggac ctgaagatgt atcagacaga gtttcaggcc atcaatgccg ccctgcagaa 2280
ccacaatcac cagcagatca tcctggacaa gggcatgctg gtggccatcg atgagctgat 2340
gcagtccctg aaccacaatg gcgagacact gaggcagaag cctccagtgg gcgaggccga 2400
tccttaccgc gtgaagatga agctgtgcat cctgctgcac gccttcagca caagggtggt 2460
gaccatcaac cgcgtgatgg gctatctgag ctccgccgga ggaggaggaa gcggcggagg 2520
aggcagcggc ggcggcggca gcggctccgg cgccaccaac ttttctctgc tgaagcaggc 2580
aggcgacgtg gaggagaatc caggacccat gaggatcagc aagccacacc tgcgctctat 2640
cagcatccag tgctacctgt gcctgctgct gaatagccac ttcctgacag aggccggcat 2700
ccacgtgttc atcctgggct gtttttccgc cggcctgcca aagaccgagg ccaactgggt 2760
gaatgtgatc tctgacctga agaagatcga ggatctgatc cagagcatgc acatcgacgc 2820
cacactgtat accgagtctg atgtgcaccc cagctgcaag gtgaccgcca tgaagtgttt 2880
tctgctggag ctgcaggtca tcagcctgga gtctggcgac gcctccatcc acgatacagt 2940
ggagaacctg atcatcctgg ccaacaatag cctgtctagc aacggcaatg tgaccgagtc 3000
cggctgcaag gagtgtgagg agctggagga gaagaacatc aaggagttcc tgcagagctt 3060
tgtgcacatc gtgcagatgt tcatcaatac ctccggcggc ggaggatctg gcggcggcgg 3120
ctccggcggg ggaggatcct gcggcggcaa ggtgtctgcc ctgaaggaga aggtgagcgc 3180
cctgaaggaa aaggtgtccg ccctgaagga gaaggtgtct gccctgaagg aaaaggtgag 3240
cgccctgaag gagggcggcg gaggatctgg gggcggcggc tccgggggag gaggatccgg 3300
ctctggcgcc acaaacttct ccctgctgaa gcaggccggc gacgtggaag aaaatcctgg 3360
accaatggca cctaggagag caaggggatg cagaaccctg ggcctgccag ccctgttatt 3420
actgctgctg ctgaggcccc ctgcaacaag gggaatcacc tgtccacccc ctatgagcgt 3480
ggagcacgcc gacatctggg tgaagagcta ctccctgtat tctcgggaga gatacatctg 3540
caatagcggc tttaagcgga aggccggcac atcctctctg accgagtgcg tgctgaacaa 3600
ggccaccaat gtggcccact ggaccacacc ctccctgaag tgcatcagag atggcggcgg 3660
cggatccgga ggaggcgggt ctggcggcgg cggcagcgag gtgtccgccc tggagaagga 3720
ggtgagcgcc ctggaaaaag aggtgagtgc tctggaaaag gaagtgtctg ccctggaaaa 3780
ggaagtgtct gccctggaaa aatgagat 3808
<210> 567
<211> 4247
<212> DNA
<213> 人工序列
<220>
<223> 合成序列
<400> 567
acattgatta ttgactagtt attaatagta atcaattacg gggtcattag ttcatagccc 60
atatatggag ttccgcgtta cataacttac ggtaaatggc ccgcctggct gaccgcccaa 120
cgacccccgc ccattgacgt caataatgac gtatgttccc atagtaacgc caatagggac 180
tttccattga cgtcaatggg tggagtattt acggtaaact gcccacttgg cagtacatca 240
agtgtatcat atgccaagta cgccccctat tgacgtcaat gacggtaaat ggcccgcctg 300
gcattatgcc cagtacatga ccttatggga ctttcctact tggcagtaca tctacgtatt 360
agtcatcgct attaccatgg tgatgcggtt ttggcagtac atcaatgggc gtggatagcg 420
gtttgactca cggggatttc caagtctcca ccccattgac gtcaatggga gtttgttttg 480
gcaccaaaat caacgggact ttccaaaatg tcgtaacaac tccgccccat tgacgcaaat 540
gggcggtagg cgtgtacggt gggaggtcta tataagcaga gctctctggc taactagaga 600
acccactgct tactggctta tcgaaattaa tacgactcac tatagggaga cccaagctgg 660
ctagcgttta aacttaagct tggtaccgag ctcggatcca ctagtccagt gtggtggaat 720
tcgccaccat gtgcccccag aaactgacaa tctcttggtt cgcaatcgtg ctgctggtct 780
cacccctgat ggctatgtgg gagctggaaa aggatgtgta cgtggtggag gtggactgga 840
caccagatgc ccccggcgag acagtgaacc tgacatgcga cacccccgag gaggacgaca 900
tcacctggac atccgatcag cggcacggcg tgatcggctc tggcaagacc ctgacaatca 960
ccgtgaagga gttcctggac gccggccagt acacatgtca caagggcggc gagacactgt 1020
cccactctca cctgctgctg cacaagaagg agaacggcat ctggagcaca gagatcctga 1080
agaacttcaa gaataagacc tttctgaagt gcgaggcccc aaattattcc ggcaggttca 1140
cctgttcttg gctggtgcag cgcaacatgg acctgaagtt taatatcaag agctcctcta 1200
gctcccccga ttccagggca gtgacatgcg gaatggcaag cctgtccgcc gagaaggtga 1260
ccctggacca gagggattac gagaagtatt ctgtgagctg ccaggaggat gtgacatgtc 1320
ctaccgccga ggagacactg ccaatcgagc tggccctgga ggccaggcag cagaacaagt 1380
acgagaatta ttccacctct ttctttatcc gcgacatcat caagccagat ccccctaaga 1440
acctgcagat gaagcccctg aagaacagcc aggtcgaggt gagctgggag tacccagaca 1500
gctggtccac accccactcc tatttctctc tgaagttctt tgtgaggatc cagcgcaaga 1560
aggagaagat gaaggagaca gaggagggct gtaaccagaa gggcgccttt ctggtggaga 1620
agacatccac cgaggtgcag tgcaagggag gaaacgtgtg cgtgcaggca caggatagat 1680
actataattc tagctgcagc aagtgggcct gcgtgccttg tagggtgcgc tccggaggcg 1740
gcggctctgg aggaggagga agcggaggag gaggaagcat gtgccagtcc cggtacctgc 1800
tgttcctggc caccctggcc ctgctgaacc acctgtctct ggccagagtg atccctgtga 1860
gcggaccagc aaggtgcctg tctcagagca gaaatctgct gaagaccaca gacgatatgg 1920
tgaagacagc ccgggagaag ctgaagcact atagctgtac cgccgaggac atcgatcacg 1980
aggacatcac aagagatcag acatccaccc tgaagacctg cctgcccctg gagctgcaca 2040
agaacgagtc ttgtctggcc acacgggaga caagctctac cacaagaggc tcctgcctgc 2100
caccccagaa gacatctctg atgatgaccc tgtgcctggg cagcatctac gaggacctga 2160
agatgtatca gaccgagttt caggccatca atgccgccct gcagaaccac aatcaccagc 2220
agatcatcct ggacaagggc atgctggtgg ccatcgatga gctgatgcag agcctgaacc 2280
acaatggcga gacactgagg cagaagcctc cagtgggaga ggcagatcca tacagagtga 2340
agatgaagct gtgcatcctg ctgcacgcct tctccacaag ggtggtgacc atcaaccgcg 2400
tgatgggcta tctgagctcc gccggaggag gaggatccgg cggaggaggc tctggcggcg 2460
gcggctccgg ctctggcgcc accaactttt ctctgctgaa gcaggcaggc gacgtggagg 2520
agaatccagg acccatgagg atcagcaagc cccacctgcg cagcatctcc atccagtgct 2580
acctgtgcct gctgctgaat agccacttcc tgacagaggc cggcatccac gtgttcatcc 2640
tgggctgttt ttccgccggc ctgcctaaga ccgaggccaa ctgggtgaat gtgatctctg 2700
acctgaagaa gatcgaggat ctgatccaga gcatgcacat cgacgccaca ctgtataccg 2760
agagcgatgt gcacccatcc tgcaaggtga ccgccatgaa gtgttttctg ctggagctgc 2820
aggtcatcag cctggagtcc ggcgacgcaa gcatccacga tacagtggag aacctgatca 2880
tcctggccaa caatagcctg tctagcaacg gcaatgtgac cgagtccggc tgcaaggagt 2940
gtgaggagct ggaggagaag aacatcaagg agttcctgca gtcctttgtg cacatcgtgc 3000
agatgttcat caatacttcc ggcggcggcg gcagtggcgg aggaggaagc ggaggcggcg 3060
gctcttgcgg cggcaaggtg agcgccctga aggagaaggt gtccgccctg aaggaaaagg 3120
tgtctgccct gaaggagaag gtgagcgccc tgaaggaaaa ggtgtccgcc ctgaaggagg 3180
ggggcggcgg cagcggcgga ggagggagcg ggggaggcgg ctctggcagc ggcgccacaa 3240
acttcagcct gctgaagcag gccggcgacg tggaagaaaa tcctggacca atggcaccta 3300
ggagagcaag gggatgcaga accctgggcc tgccagccct gttattactg ctgctgctga 3360
ggccccctgc aacaagggga atcacctgtc caccccctat gagcgtggag cacgccgaca 3420
tctgggtgaa gtcctactct ctgtatagcc gggagagata catctgcaat tccggcttta 3480
agaggaaggc cggcacatcc tctctgaccg agtgcgtgct gaacaaggcc accaatgtgg 3540
cccactggac cacaccatcc ctgaagtgca tccgggaccc cgccctggtg caccagcggc 3600
ccgcaccacc atctacagtg accacagcag gagtgacccc acagcctgag agcctgtccc 3660
catctggcaa ggagccagca gcaagctccc cttctagcaa caatacagca gcaaccacag 3720
cagcaatcgt gcctggctcc cagctgatgc ccagcaagtc cccttctacc ggcaccacag 3780
agatctcctc tcacgagagc tcccacggca cacccagcca gaccacagcc aagaactggg 3840
agctgaccgc aagcgcctcc caccagcctc caggcgtgta ccctcagggc cactccgata 3900
ccacagtggc catctctaca agcaccgtgc tgctgtgcgg cctgtctgcc gtgagcctgc 3960
tggcctgtta tctgaagtct aggcagaccc cacctctggc aagcgtggag atggaggcaa 4020
tggaggccct gccagtgaca tggggcacct ctagccgcga cgaggatctg gagaattgca 4080
gccaccacct gggaggagga ggatcaggcg gcggcgggtc cggcggcggc ggatccgagg 4140
tgtctgccct ggagaaggag gtgtccgccc tggaaaaaga agtgtcagcc ctggagaaag 4200
aagtgtcagc cctggaaaaa gaggtgtctg ccctggaaaa ataagat 4247
<210> 568
<211> 897
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 568
Met Cys Pro Gln Lys Leu Thr Ile Ser Trp Phe Ala Ile Val Leu Leu
1 5 10 15
Val Ser Pro Leu Met Ala Met Trp Glu Leu Glu Lys Asp Val Tyr Val
20 25 30
Val Glu Val Asp Trp Thr Pro Asp Ala Pro Gly Glu Thr Val Asn Leu
35 40 45
Thr Cys Asp Thr Pro Glu Glu Asp Asp Ile Thr Trp Thr Ser Asp Gln
50 55 60
Arg His Gly Val Ile Gly Ser Gly Lys Thr Leu Thr Ile Thr Val Lys
65 70 75 80
Glu Phe Leu Asp Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Thr
85 90 95
Leu Ser His Ser His Leu Leu Leu His Lys Lys Glu Asn Gly Ile Trp
100 105 110
Ser Thr Glu Ile Leu Lys Asn Phe Lys Asn Lys Thr Phe Leu Lys Cys
115 120 125
Glu Ala Pro Asn Tyr Ser Gly Arg Phe Thr Cys Ser Trp Leu Val Gln
130 135 140
Arg Asn Met Asp Leu Lys Phe Asn Ile Lys Ser Ser Ser Ser Ser Pro
145 150 155 160
Asp Ser Arg Ala Val Thr Cys Gly Met Ala Ser Leu Ser Ala Glu Lys
165 170 175
Val Thr Leu Asp Gln Arg Asp Tyr Glu Lys Tyr Ser Val Ser Cys Gln
180 185 190
Glu Asp Val Thr Cys Pro Thr Ala Glu Glu Thr Leu Pro Ile Glu Leu
195 200 205
Ala Leu Glu Ala Arg Gln Gln Asn Lys Tyr Glu Asn Tyr Ser Thr Ser
210 215 220
Phe Phe Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln
225 230 235 240
Met Lys Pro Leu Lys Asn Ser Gln Val Glu Val Ser Trp Glu Tyr Pro
245 250 255
Asp Ser Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Lys Phe Phe Val
260 265 270
Arg Ile Gln Arg Lys Lys Glu Lys Met Lys Glu Thr Glu Glu Gly Cys
275 280 285
Asn Gln Lys Gly Ala Phe Leu Val Glu Lys Thr Ser Thr Glu Val Gln
290 295 300
Cys Lys Gly Gly Asn Val Cys Val Gln Ala Gln Asp Arg Tyr Tyr Asn
305 310 315 320
Ser Ser Cys Ser Lys Trp Ala Cys Val Pro Cys Arg Val Arg Ser Gly
325 330 335
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Met Cys
340 345 350
Gln Ser Arg Tyr Leu Leu Phe Leu Ala Thr Leu Ala Leu Leu Asn His
355 360 365
Leu Ser Leu Ala Arg Val Ile Pro Val Ser Gly Pro Ala Arg Cys Leu
370 375 380
Ser Gln Ser Arg Asn Leu Leu Lys Thr Thr Asp Asp Met Val Lys Thr
385 390 395 400
Ala Arg Glu Lys Leu Lys His Tyr Ser Cys Thr Ala Glu Asp Ile Asp
405 410 415
His Glu Asp Ile Thr Arg Asp Gln Thr Ser Thr Leu Lys Thr Cys Leu
420 425 430
Pro Leu Glu Leu His Lys Asn Glu Ser Cys Leu Ala Thr Arg Glu Thr
435 440 445
Ser Ser Thr Thr Arg Gly Ser Cys Leu Pro Pro Gln Lys Thr Ser Leu
450 455 460
Met Met Thr Leu Cys Leu Gly Ser Ile Tyr Glu Asp Leu Lys Met Tyr
465 470 475 480
Gln Thr Glu Phe Gln Ala Ile Asn Ala Ala Leu Gln Asn His Asn His
485 490 495
Gln Gln Ile Ile Leu Asp Lys Gly Met Leu Val Ala Ile Asp Glu Leu
500 505 510
Met Gln Ser Leu Asn His Asn Gly Glu Thr Leu Arg Gln Lys Pro Pro
515 520 525
Val Gly Glu Ala Asp Pro Tyr Arg Val Lys Met Lys Leu Cys Ile Leu
530 535 540
Leu His Ala Phe Ser Thr Arg Val Val Thr Ile Asn Arg Val Met Gly
545 550 555 560
Tyr Leu Ser Ser Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
565 570 575
Gly Gly Gly Ser Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln
580 585 590
Ala Gly Asp Val Glu Glu Asn Pro Gly Pro Met Arg Ile Ser Lys Pro
595 600 605
His Leu Arg Ser Ile Ser Ile Gln Cys Tyr Leu Cys Leu Leu Leu Asn
610 615 620
Ser His Phe Leu Thr Glu Ala Gly Ile His Val Phe Ile Leu Gly Cys
625 630 635 640
Phe Ser Ala Gly Leu Pro Lys Thr Glu Ala Asn Trp Val Asn Val Ile
645 650 655
Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile Gln Ser Met His Ile Asp
660 665 670
Ala Thr Leu Tyr Thr Glu Ser Asp Val His Pro Ser Cys Lys Val Thr
675 680 685
Ala Met Lys Cys Phe Leu Leu Glu Leu Gln Val Ile Ser Leu Glu Ser
690 695 700
Gly Asp Ala Ser Ile His Asp Thr Val Glu Asn Leu Ile Ile Leu Ala
705 710 715 720
Asn Asn Ser Leu Ser Ser Asn Gly Asn Val Thr Glu Ser Gly Cys Lys
725 730 735
Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile Lys Glu Phe Leu Gln Ser
740 745 750
Phe Val His Ile Val Gln Met Phe Ile Asn Thr Ser Gly Gly Gly Gly
755 760 765
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Ser Gly Ala Thr
770 775 780
Asn Phe Ser Leu Leu Lys Gln Ala Gly Asp Val Glu Glu Asn Pro Gly
785 790 795 800
Pro Met Ala Pro Arg Arg Ala Arg Gly Cys Arg Thr Leu Gly Leu Pro
805 810 815
Ala Leu Leu Leu Leu Leu Leu Leu Arg Pro Pro Ala Thr Arg Gly Ile
820 825 830
Thr Cys Pro Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val Lys
835 840 845
Ser Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly Phe
850 855 860
Lys Arg Lys Ala Gly Thr Ser Ser Leu Thr Glu Cys Val Leu Asn Lys
865 870 875 880
Ala Thr Asn Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys Ile Arg
885 890 895
Asp
<210> 569
<211> 1068
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 569
Met Cys Pro Gln Lys Leu Thr Ile Ser Trp Phe Ala Ile Val Leu Leu
1 5 10 15
Val Ser Pro Leu Met Ala Met Trp Glu Leu Glu Lys Asp Val Tyr Val
20 25 30
Val Glu Val Asp Trp Thr Pro Asp Ala Pro Gly Glu Thr Val Asn Leu
35 40 45
Thr Cys Asp Thr Pro Glu Glu Asp Asp Ile Thr Trp Thr Ser Asp Gln
50 55 60
Arg His Gly Val Ile Gly Ser Gly Lys Thr Leu Thr Ile Thr Val Lys
65 70 75 80
Glu Phe Leu Asp Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Thr
85 90 95
Leu Ser His Ser His Leu Leu Leu His Lys Lys Glu Asn Gly Ile Trp
100 105 110
Ser Thr Glu Ile Leu Lys Asn Phe Lys Asn Lys Thr Phe Leu Lys Cys
115 120 125
Glu Ala Pro Asn Tyr Ser Gly Arg Phe Thr Cys Ser Trp Leu Val Gln
130 135 140
Arg Asn Met Asp Leu Lys Phe Asn Ile Lys Ser Ser Ser Ser Ser Pro
145 150 155 160
Asp Ser Arg Ala Val Thr Cys Gly Met Ala Ser Leu Ser Ala Glu Lys
165 170 175
Val Thr Leu Asp Gln Arg Asp Tyr Glu Lys Tyr Ser Val Ser Cys Gln
180 185 190
Glu Asp Val Thr Cys Pro Thr Ala Glu Glu Thr Leu Pro Ile Glu Leu
195 200 205
Ala Leu Glu Ala Arg Gln Gln Asn Lys Tyr Glu Asn Tyr Ser Thr Ser
210 215 220
Phe Phe Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln
225 230 235 240
Met Lys Pro Leu Lys Asn Ser Gln Val Glu Val Ser Trp Glu Tyr Pro
245 250 255
Asp Ser Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Lys Phe Phe Val
260 265 270
Arg Ile Gln Arg Lys Lys Glu Lys Met Lys Glu Thr Glu Glu Gly Cys
275 280 285
Asn Gln Lys Gly Ala Phe Leu Val Glu Lys Thr Ser Thr Glu Val Gln
290 295 300
Cys Lys Gly Gly Asn Val Cys Val Gln Ala Gln Asp Arg Tyr Tyr Asn
305 310 315 320
Ser Ser Cys Ser Lys Trp Ala Cys Val Pro Cys Arg Val Arg Ser Gly
325 330 335
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Met Cys
340 345 350
Gln Ser Arg Tyr Leu Leu Phe Leu Ala Thr Leu Ala Leu Leu Asn His
355 360 365
Leu Ser Leu Ala Arg Val Ile Pro Val Ser Gly Pro Ala Arg Cys Leu
370 375 380
Ser Gln Ser Arg Asn Leu Leu Lys Thr Thr Asp Asp Met Val Lys Thr
385 390 395 400
Ala Arg Glu Lys Leu Lys His Tyr Ser Cys Thr Ala Glu Asp Ile Asp
405 410 415
His Glu Asp Ile Thr Arg Asp Gln Thr Ser Thr Leu Lys Thr Cys Leu
420 425 430
Pro Leu Glu Leu His Lys Asn Glu Ser Cys Leu Ala Thr Arg Glu Thr
435 440 445
Ser Ser Thr Thr Arg Gly Ser Cys Leu Pro Pro Gln Lys Thr Ser Leu
450 455 460
Met Met Thr Leu Cys Leu Gly Ser Ile Tyr Glu Asp Leu Lys Met Tyr
465 470 475 480
Gln Thr Glu Phe Gln Ala Ile Asn Ala Ala Leu Gln Asn His Asn His
485 490 495
Gln Gln Ile Ile Leu Asp Lys Gly Met Leu Val Ala Ile Asp Glu Leu
500 505 510
Met Gln Ser Leu Asn His Asn Gly Glu Thr Leu Arg Gln Lys Pro Pro
515 520 525
Val Gly Glu Ala Asp Pro Tyr Arg Val Lys Met Lys Leu Cys Ile Leu
530 535 540
Leu His Ala Phe Ser Thr Arg Val Val Thr Ile Asn Arg Val Met Gly
545 550 555 560
Tyr Leu Ser Ser Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
565 570 575
Gly Gly Gly Ser Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln
580 585 590
Ala Gly Asp Val Glu Glu Asn Pro Gly Pro Met Arg Ile Ser Lys Pro
595 600 605
His Leu Arg Ser Ile Ser Ile Gln Cys Tyr Leu Cys Leu Leu Leu Asn
610 615 620
Ser His Phe Leu Thr Glu Ala Gly Ile His Val Phe Ile Leu Gly Cys
625 630 635 640
Phe Ser Ala Gly Leu Pro Lys Thr Glu Ala Asn Trp Val Asn Val Ile
645 650 655
Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile Gln Ser Met His Ile Asp
660 665 670
Ala Thr Leu Tyr Thr Glu Ser Asp Val His Pro Ser Cys Lys Val Thr
675 680 685
Ala Met Lys Cys Phe Leu Leu Glu Leu Gln Val Ile Ser Leu Glu Ser
690 695 700
Gly Asp Ala Ser Ile His Asp Thr Val Glu Asn Leu Ile Ile Leu Ala
705 710 715 720
Asn Asn Ser Leu Ser Ser Asn Gly Asn Val Thr Glu Ser Gly Cys Lys
725 730 735
Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile Lys Glu Phe Leu Gln Ser
740 745 750
Phe Val His Ile Val Gln Met Phe Ile Asn Thr Ser Gly Gly Gly Gly
755 760 765
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Ser Gly Ala Thr
770 775 780
Asn Phe Ser Leu Leu Lys Gln Ala Gly Asp Val Glu Glu Asn Pro Gly
785 790 795 800
Pro Met Ala Pro Arg Arg Ala Arg Gly Cys Arg Thr Leu Gly Leu Pro
805 810 815
Ala Leu Leu Leu Leu Leu Leu Leu Arg Pro Pro Ala Thr Arg Gly Ile
820 825 830
Thr Cys Pro Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val Lys
835 840 845
Ser Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly Phe
850 855 860
Lys Arg Lys Ala Gly Thr Ser Ser Leu Thr Glu Cys Val Leu Asn Lys
865 870 875 880
Ala Thr Asn Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys Ile Arg
885 890 895
Asp Pro Ala Leu Val His Gln Arg Pro Ala Pro Pro Ser Thr Val Thr
900 905 910
Thr Ala Gly Val Thr Pro Gln Pro Glu Ser Leu Ser Pro Ser Gly Lys
915 920 925
Glu Pro Ala Ala Ser Ser Pro Ser Ser Asn Asn Thr Ala Ala Thr Thr
930 935 940
Ala Ala Ile Val Pro Gly Ser Gln Leu Met Pro Ser Lys Ser Pro Ser
945 950 955 960
Thr Gly Thr Thr Glu Ile Ser Ser His Glu Ser Ser His Gly Thr Pro
965 970 975
Ser Gln Thr Thr Ala Lys Asn Trp Glu Leu Thr Ala Ser Ala Ser His
980 985 990
Gln Pro Pro Gly Val Tyr Pro Gln Gly His Ser Asp Thr Thr Val Ala
995 1000 1005
Ile Ser Thr Ser Thr Val Leu Leu Cys Gly Leu Ser Ala Val Ser
1010 1015 1020
Leu Leu Ala Cys Tyr Leu Lys Ser Arg Gln Thr Pro Pro Leu Ala
1025 1030 1035
Ser Val Glu Met Glu Ala Met Glu Ala Leu Pro Val Thr Trp Gly
1040 1045 1050
Thr Ser Ser Arg Asp Glu Asp Leu Glu Asn Cys Ser His His Leu
1055 1060 1065
<210> 570
<211> 1000
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 570
Met Cys Pro Gln Lys Leu Thr Ile Ser Trp Phe Ala Ile Val Leu Leu
1 5 10 15
Val Ser Pro Leu Met Ala Met Trp Glu Leu Glu Lys Asp Val Tyr Val
20 25 30
Val Glu Val Asp Trp Thr Pro Asp Ala Pro Gly Glu Thr Val Asn Leu
35 40 45
Thr Cys Asp Thr Pro Glu Glu Asp Asp Ile Thr Trp Thr Ser Asp Gln
50 55 60
Arg His Gly Val Ile Gly Ser Gly Lys Thr Leu Thr Ile Thr Val Lys
65 70 75 80
Glu Phe Leu Asp Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Thr
85 90 95
Leu Ser His Ser His Leu Leu Leu His Lys Lys Glu Asn Gly Ile Trp
100 105 110
Ser Thr Glu Ile Leu Lys Asn Phe Lys Asn Lys Thr Phe Leu Lys Cys
115 120 125
Glu Ala Pro Asn Tyr Ser Gly Arg Phe Thr Cys Ser Trp Leu Val Gln
130 135 140
Arg Asn Met Asp Leu Lys Phe Asn Ile Lys Ser Ser Ser Ser Ser Pro
145 150 155 160
Asp Ser Arg Ala Val Thr Cys Gly Met Ala Ser Leu Ser Ala Glu Lys
165 170 175
Val Thr Leu Asp Gln Arg Asp Tyr Glu Lys Tyr Ser Val Ser Cys Gln
180 185 190
Glu Asp Val Thr Cys Pro Thr Ala Glu Glu Thr Leu Pro Ile Glu Leu
195 200 205
Ala Leu Glu Ala Arg Gln Gln Asn Lys Tyr Glu Asn Tyr Ser Thr Ser
210 215 220
Phe Phe Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln
225 230 235 240
Met Lys Pro Leu Lys Asn Ser Gln Val Glu Val Ser Trp Glu Tyr Pro
245 250 255
Asp Ser Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Lys Phe Phe Val
260 265 270
Arg Ile Gln Arg Lys Lys Glu Lys Met Lys Glu Thr Glu Glu Gly Cys
275 280 285
Asn Gln Lys Gly Ala Phe Leu Val Glu Lys Thr Ser Thr Glu Val Gln
290 295 300
Cys Lys Gly Gly Asn Val Cys Val Gln Ala Gln Asp Arg Tyr Tyr Asn
305 310 315 320
Ser Ser Cys Ser Lys Trp Ala Cys Val Pro Cys Arg Val Arg Ser Gly
325 330 335
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Met Cys
340 345 350
Gln Ser Arg Tyr Leu Leu Phe Leu Ala Thr Leu Ala Leu Leu Asn His
355 360 365
Leu Ser Leu Ala Arg Val Ile Pro Val Ser Gly Pro Ala Arg Cys Leu
370 375 380
Ser Gln Ser Arg Asn Leu Leu Lys Thr Thr Asp Asp Met Val Lys Thr
385 390 395 400
Ala Arg Glu Lys Leu Lys His Tyr Ser Cys Thr Ala Glu Asp Ile Asp
405 410 415
His Glu Asp Ile Thr Arg Asp Gln Thr Ser Thr Leu Lys Thr Cys Leu
420 425 430
Pro Leu Glu Leu His Lys Asn Glu Ser Cys Leu Ala Thr Arg Glu Thr
435 440 445
Ser Ser Thr Thr Arg Gly Ser Cys Leu Pro Pro Gln Lys Thr Ser Leu
450 455 460
Met Met Thr Leu Cys Leu Gly Ser Ile Tyr Glu Asp Leu Lys Met Tyr
465 470 475 480
Gln Thr Glu Phe Gln Ala Ile Asn Ala Ala Leu Gln Asn His Asn His
485 490 495
Gln Gln Ile Ile Leu Asp Lys Gly Met Leu Val Ala Ile Asp Glu Leu
500 505 510
Met Gln Ser Leu Asn His Asn Gly Glu Thr Leu Arg Gln Lys Pro Pro
515 520 525
Val Gly Glu Ala Asp Pro Tyr Arg Val Lys Met Lys Leu Cys Ile Leu
530 535 540
Leu His Ala Phe Ser Thr Arg Val Val Thr Ile Asn Arg Val Met Gly
545 550 555 560
Tyr Leu Ser Ser Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
565 570 575
Gly Gly Gly Ser Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln
580 585 590
Ala Gly Asp Val Glu Glu Asn Pro Gly Pro Met Arg Ile Ser Lys Pro
595 600 605
His Leu Arg Ser Ile Ser Ile Gln Cys Tyr Leu Cys Leu Leu Leu Asn
610 615 620
Ser His Phe Leu Thr Glu Ala Gly Ile His Val Phe Ile Leu Gly Cys
625 630 635 640
Phe Ser Ala Gly Leu Pro Lys Thr Glu Ala Asn Trp Val Asn Val Ile
645 650 655
Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile Gln Ser Met His Ile Asp
660 665 670
Ala Thr Leu Tyr Thr Glu Ser Asp Val His Pro Ser Cys Lys Val Thr
675 680 685
Ala Met Lys Cys Phe Leu Leu Glu Leu Gln Val Ile Ser Leu Glu Ser
690 695 700
Gly Asp Ala Ser Ile His Asp Thr Val Glu Asn Leu Ile Ile Leu Ala
705 710 715 720
Asn Asn Ser Leu Ser Ser Asn Gly Asn Val Thr Glu Ser Gly Cys Lys
725 730 735
Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile Lys Glu Phe Leu Gln Ser
740 745 750
Phe Val His Ile Val Gln Met Phe Ile Asn Thr Ser Gly Gly Gly Gly
755 760 765
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Cys Gly Gly Lys Val
770 775 780
Ser Ala Leu Lys Glu Lys Val Ser Ala Leu Lys Glu Lys Val Ser Ala
785 790 795 800
Leu Lys Glu Lys Val Ser Ala Leu Lys Glu Lys Val Ser Ala Leu Lys
805 810 815
Glu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
820 825 830
Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln Ala Gly Asp Val
835 840 845
Glu Glu Asn Pro Gly Pro Met Ala Pro Arg Arg Ala Arg Gly Cys Arg
850 855 860
Thr Leu Gly Leu Pro Ala Leu Leu Leu Leu Leu Leu Leu Arg Pro Pro
865 870 875 880
Ala Thr Arg Gly Ile Thr Cys Pro Pro Pro Met Ser Val Glu His Ala
885 890 895
Asp Ile Trp Val Lys Ser Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile
900 905 910
Cys Asn Ser Gly Phe Lys Arg Lys Ala Gly Thr Ser Ser Leu Thr Glu
915 920 925
Cys Val Leu Asn Lys Ala Thr Asn Val Ala His Trp Thr Thr Pro Ser
930 935 940
Leu Lys Cys Ile Arg Asp Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
945 950 955 960
Gly Gly Gly Gly Ser Glu Val Ser Ala Leu Glu Lys Glu Val Ser Ala
965 970 975
Leu Glu Lys Glu Val Ser Ala Leu Glu Lys Glu Val Ser Ala Leu Glu
980 985 990
Lys Glu Val Ser Ala Leu Glu Lys
995 1000
<210> 571
<211> 1171
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 571
Met Cys Pro Gln Lys Leu Thr Ile Ser Trp Phe Ala Ile Val Leu Leu
1 5 10 15
Val Ser Pro Leu Met Ala Met Trp Glu Leu Glu Lys Asp Val Tyr Val
20 25 30
Val Glu Val Asp Trp Thr Pro Asp Ala Pro Gly Glu Thr Val Asn Leu
35 40 45
Thr Cys Asp Thr Pro Glu Glu Asp Asp Ile Thr Trp Thr Ser Asp Gln
50 55 60
Arg His Gly Val Ile Gly Ser Gly Lys Thr Leu Thr Ile Thr Val Lys
65 70 75 80
Glu Phe Leu Asp Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Thr
85 90 95
Leu Ser His Ser His Leu Leu Leu His Lys Lys Glu Asn Gly Ile Trp
100 105 110
Ser Thr Glu Ile Leu Lys Asn Phe Lys Asn Lys Thr Phe Leu Lys Cys
115 120 125
Glu Ala Pro Asn Tyr Ser Gly Arg Phe Thr Cys Ser Trp Leu Val Gln
130 135 140
Arg Asn Met Asp Leu Lys Phe Asn Ile Lys Ser Ser Ser Ser Ser Pro
145 150 155 160
Asp Ser Arg Ala Val Thr Cys Gly Met Ala Ser Leu Ser Ala Glu Lys
165 170 175
Val Thr Leu Asp Gln Arg Asp Tyr Glu Lys Tyr Ser Val Ser Cys Gln
180 185 190
Glu Asp Val Thr Cys Pro Thr Ala Glu Glu Thr Leu Pro Ile Glu Leu
195 200 205
Ala Leu Glu Ala Arg Gln Gln Asn Lys Tyr Glu Asn Tyr Ser Thr Ser
210 215 220
Phe Phe Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln
225 230 235 240
Met Lys Pro Leu Lys Asn Ser Gln Val Glu Val Ser Trp Glu Tyr Pro
245 250 255
Asp Ser Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Lys Phe Phe Val
260 265 270
Arg Ile Gln Arg Lys Lys Glu Lys Met Lys Glu Thr Glu Glu Gly Cys
275 280 285
Asn Gln Lys Gly Ala Phe Leu Val Glu Lys Thr Ser Thr Glu Val Gln
290 295 300
Cys Lys Gly Gly Asn Val Cys Val Gln Ala Gln Asp Arg Tyr Tyr Asn
305 310 315 320
Ser Ser Cys Ser Lys Trp Ala Cys Val Pro Cys Arg Val Arg Ser Gly
325 330 335
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Met Cys
340 345 350
Gln Ser Arg Tyr Leu Leu Phe Leu Ala Thr Leu Ala Leu Leu Asn His
355 360 365
Leu Ser Leu Ala Arg Val Ile Pro Val Ser Gly Pro Ala Arg Cys Leu
370 375 380
Ser Gln Ser Arg Asn Leu Leu Lys Thr Thr Asp Asp Met Val Lys Thr
385 390 395 400
Ala Arg Glu Lys Leu Lys His Tyr Ser Cys Thr Ala Glu Asp Ile Asp
405 410 415
His Glu Asp Ile Thr Arg Asp Gln Thr Ser Thr Leu Lys Thr Cys Leu
420 425 430
Pro Leu Glu Leu His Lys Asn Glu Ser Cys Leu Ala Thr Arg Glu Thr
435 440 445
Ser Ser Thr Thr Arg Gly Ser Cys Leu Pro Pro Gln Lys Thr Ser Leu
450 455 460
Met Met Thr Leu Cys Leu Gly Ser Ile Tyr Glu Asp Leu Lys Met Tyr
465 470 475 480
Gln Thr Glu Phe Gln Ala Ile Asn Ala Ala Leu Gln Asn His Asn His
485 490 495
Gln Gln Ile Ile Leu Asp Lys Gly Met Leu Val Ala Ile Asp Glu Leu
500 505 510
Met Gln Ser Leu Asn His Asn Gly Glu Thr Leu Arg Gln Lys Pro Pro
515 520 525
Val Gly Glu Ala Asp Pro Tyr Arg Val Lys Met Lys Leu Cys Ile Leu
530 535 540
Leu His Ala Phe Ser Thr Arg Val Val Thr Ile Asn Arg Val Met Gly
545 550 555 560
Tyr Leu Ser Ser Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
565 570 575
Gly Gly Gly Ser Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln
580 585 590
Ala Gly Asp Val Glu Glu Asn Pro Gly Pro Met Arg Ile Ser Lys Pro
595 600 605
His Leu Arg Ser Ile Ser Ile Gln Cys Tyr Leu Cys Leu Leu Leu Asn
610 615 620
Ser His Phe Leu Thr Glu Ala Gly Ile His Val Phe Ile Leu Gly Cys
625 630 635 640
Phe Ser Ala Gly Leu Pro Lys Thr Glu Ala Asn Trp Val Asn Val Ile
645 650 655
Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile Gln Ser Met His Ile Asp
660 665 670
Ala Thr Leu Tyr Thr Glu Ser Asp Val His Pro Ser Cys Lys Val Thr
675 680 685
Ala Met Lys Cys Phe Leu Leu Glu Leu Gln Val Ile Ser Leu Glu Ser
690 695 700
Gly Asp Ala Ser Ile His Asp Thr Val Glu Asn Leu Ile Ile Leu Ala
705 710 715 720
Asn Asn Ser Leu Ser Ser Asn Gly Asn Val Thr Glu Ser Gly Cys Lys
725 730 735
Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile Lys Glu Phe Leu Gln Ser
740 745 750
Phe Val His Ile Val Gln Met Phe Ile Asn Thr Ser Gly Gly Gly Gly
755 760 765
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Cys Gly Gly Lys Val
770 775 780
Ser Ala Leu Lys Glu Lys Val Ser Ala Leu Lys Glu Lys Val Ser Ala
785 790 795 800
Leu Lys Glu Lys Val Ser Ala Leu Lys Glu Lys Val Ser Ala Leu Lys
805 810 815
Glu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
820 825 830
Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln Ala Gly Asp Val
835 840 845
Glu Glu Asn Pro Gly Pro Met Ala Pro Arg Arg Ala Arg Gly Cys Arg
850 855 860
Thr Leu Gly Leu Pro Ala Leu Leu Leu Leu Leu Leu Leu Arg Pro Pro
865 870 875 880
Ala Thr Arg Gly Ile Thr Cys Pro Pro Pro Met Ser Val Glu His Ala
885 890 895
Asp Ile Trp Val Lys Ser Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile
900 905 910
Cys Asn Ser Gly Phe Lys Arg Lys Ala Gly Thr Ser Ser Leu Thr Glu
915 920 925
Cys Val Leu Asn Lys Ala Thr Asn Val Ala His Trp Thr Thr Pro Ser
930 935 940
Leu Lys Cys Ile Arg Asp Pro Ala Leu Val His Gln Arg Pro Ala Pro
945 950 955 960
Pro Ser Thr Val Thr Thr Ala Gly Val Thr Pro Gln Pro Glu Ser Leu
965 970 975
Ser Pro Ser Gly Lys Glu Pro Ala Ala Ser Ser Pro Ser Ser Asn Asn
980 985 990
Thr Ala Ala Thr Thr Ala Ala Ile Val Pro Gly Ser Gln Leu Met Pro
995 1000 1005
Ser Lys Ser Pro Ser Thr Gly Thr Thr Glu Ile Ser Ser His Glu
1010 1015 1020
Ser Ser His Gly Thr Pro Ser Gln Thr Thr Ala Lys Asn Trp Glu
1025 1030 1035
Leu Thr Ala Ser Ala Ser His Gln Pro Pro Gly Val Tyr Pro Gln
1040 1045 1050
Gly His Ser Asp Thr Thr Val Ala Ile Ser Thr Ser Thr Val Leu
1055 1060 1065
Leu Cys Gly Leu Ser Ala Val Ser Leu Leu Ala Cys Tyr Leu Lys
1070 1075 1080
Ser Arg Gln Thr Pro Pro Leu Ala Ser Val Glu Met Glu Ala Met
1085 1090 1095
Glu Ala Leu Pro Val Thr Trp Gly Thr Ser Ser Arg Asp Glu Asp
1100 1105 1110
Leu Glu Asn Cys Ser His His Leu Gly Gly Gly Gly Ser Gly Gly
1115 1120 1125
Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Ser Ala Leu Glu Lys
1130 1135 1140
Glu Val Ser Ala Leu Glu Lys Glu Val Ser Ala Leu Glu Lys Glu
1145 1150 1155
Val Ser Ala Leu Glu Lys Glu Val Ser Ala Leu Glu Lys
1160 1165 1170
<210> 572
<211> 1230
<212> DNA
<213> 单纯疱疹病毒
<400> 572
gtgacgattc ccccaatggc cgcgcgtccc aggggaggca ggcccaccgc ggggcggccc 60
cgtccccggg gaccaacccg gcgcccccaa agaatatcat tagcatgcac ggcccggccc 120
ccgatttggg ggcccaaccc ggtgtccccc aaagaacccc attagcatgc ccctcccgcc 180
gacgcaacag gggcttggcc tgcgtcggtg ccccggggct tcccgccttc ccgaagaaac 240
tcattaccat acccggaacc ccaggggacc aatgcgggtt cattgagcga cccgcgggcc 300
aatgcgcgag gggccgtgtg ttccgccaaa aaagcaatta gcataacccg gaaccccagg 360
ggagtggtta cgcgcggcgc gggaggcggg gaataccggg gttgcccatt aagggccgcg 420
ggaattgccg gaagcgggaa gggcggccgg ggccgcccat tagttacctg ggactgtgcg 480
gttgggacgg cgcccgtggg cccgggcggc cgggggcggc gggggccgcg atggcggcgg 540
cggcgggcca tggagacaga gagcgtgccg gggtggtaga gtttgacagg caagcatgtg 600
cgtgcagagg cgagtagtgc ttgcctgtct aactcgctag tctcggccgc ggggggcccg 660
ggctgcccgc cgccgccgct ttaaagggcc gcgcgcgacc cccggggggt gtgttttggg 720
gggggcccgt tttcggggtc tggccgctcc tccccccgct cctccccccg ctcctccccc 780
cgctcctccc cccgctcctc cccccgctcc tccccccgct cctccccccg ctcctccccc 840
cgctcctccc cccgctcctc cccccgctcc tccccccgct cctccccccg ctcctccccc 900
cgctcctccc cccgctcctc cccccgctcc tccccccgct cctccccccg ctcctccccc 960
cgctcccgcg gccccgcccc ccacgcccgc cgcgcgcgcg cacgccgccc ggaccgccgc 1020
ccgccttttt tgcgcgcgcg cgcgcccgcg gggggcccgg gctgccacag gtgaaaccaa 1080
cagagcacgg cgcactccgc acgtcacacg tcacgtcatc caccacacct gcccaacaac 1140
acaactcaca gcgacaactc accgcgcaac aactcctgtt cctcatccac acgtcaccgc 1200
gcacctcccg ctcctccaga cgtaccccgg 1230
<210> 573
<211> 3185
<212> DNA
<213> 单纯疱疹病毒
<400> 573
atgctcgccg tccgttccct gcagcacctc tcaaccgtcg tcttgataac ggcgtacggc 60
ctcgtgctcg tgtggtacac cgtcttcggt gccagtccgc tgcaccgatg tatttacgcg 120
gtacgcccca ccggcaccaa caacgacacc gccctcgtgt ggatgaaaat gaaccagacc 180
ctattgtttc tgggggcccc gacgcacccc cccaacgggg gctggcgcaa ccacgcccat 240
atctgctacg ccaatcttat cgcgggtagg gtcgtgccct tccaggtccc acctgacgcc 300
atgaatcgtc ggatcatgaa cgtccacgag gcagttaact gtctggagac cctatggtac 360
acacgggtgc gtctggtggt cgtagggtgg ttcctgtatc tggcgttcgt cgccctccac 420
caacgccgat gtatgtttgg cgtcgtgagt cccgcccaca agatggtggc cccggccacc 480
tacctcttga actacgcagg ccgcatcgta tcgagcgtgt tcctgcagta cccctacacg 540
aaaattaccc gcctgctctg cgagctgtcg gtccagcggc aaaacctggt tcagttgttt 600
gagacggacc cggtcacctt cttgtaccac cgccccgcca tcggggtcat cgtaggctgc 660
gagttgatgc tacgctttgt ggccgtgggt ctcatcgtcg gcaccgcttt catatcccgg 720
ggggcatgtg cgatcacata ccccctgttt ctgaccatca ccacctggtg ttttgtctcc 780
accatcggcc tgacagagct gtattgtatt ctgcggcggg gcccggcccc caagaacgca 840
gacaaggccg ccgccccggg gcgatccaag gggctgtcgg gcgtctgcgg gcgctgctgt 900
tccatcatcc tctcgggcat cgcagtgcga ttgtgttata tcgccgtggt ggccggggtg 960
gtgctcgtgg cgcttcacta cgagcaggag atccagaggc gcctgtttga tgtatgacgt 1020
cacatccagg ccggcggaaa ccgtaacggc atatgcaaat tggaaactgt cctgtcttgg 1080
ggcccaccca cccgacgcgt catatgcaaa tgaaaatcgg tcccccgagg ccacgtgtag 1140
cctggatccc aacgaccccg cccatgggtc ccaattggcc gtcccgttac caagaccaac 1200
ccagccagca tatccacccc cgcccgggtc cccgcggaag cggaacgggg tatgtgatat 1260
gctaattaaa tacgggaatt tccggggact ttccgggaat ttccggggac tttccgggaa 1320
tttccctaca gaggtgcata ttaacagagc ttttgtcctg gagaatgcca cgtacttatg 1380
gtgtctgatt ggtccttgtc tgtgccggag gtggggcggg ggccccgccc ggggggcgga 1440
acgaggaggg gtttgggaga gccggccccg gcaccacggg tataaggaca tccaccaccc 1500
ggccggtggt ggtgtgcagc cgtgttccaa ccacggtcac gcttcggtgc ctctccccga 1560
ttcgggcccg gtcgctcgct accggtgcgc caccaccaga ggccatatcc gacaccccag 1620
ccccgacggc agccgacagc ccggtcatgg cgactgacat tgatatgcta attgacctcg 1680
gcctggacct ctccgacagc gatctggacg aggacccccc cgagccggcg gagagccgcc 1740
gcgacgacct ggaatcggac agcagcgggg agtgttcctc gtcggacgag gacatggaag 1800
acccccacgg agaggacgga ccggagccga tactcgacgc cgctcgcccg gcggtccgcc 1860
cgtctcgtcc agaagacccc ggcgtaccca gcacccagac gcctcgtccg acggagcggc 1920
agggccccaa cgatcctcaa ccagcgcccc acagtgtgtg gtcgcgcctc ggggcccggc 1980
gaccgtcttg ctcccccgag cagcacgggg gcaaggtggc ccgcctccaa cccccaccga 2040
ccaaagccca gcctgcccgc ggcggacgcc gtgggcgtcg caggggtcgg ggtcgcggtg 2100
gtcccggggc tgccgatggt ttgtcggacc cccgccggcg tgcccccaga accaatcgca 2160
accctggggg accccgcccc ggggcggggt ggacggacgg ccccggcgcc ccccatggcg 2220
aggcgtggcg cggcagtgag cagcccgacc cacccggagg ccagcggaca cggggcgtgc 2280
gccaagcacc ccccccgcta atgacgctgg cgattgcccc cccgcccgcg gacccccgcg 2340
ccccggcccc ggagcgaaag gcgcccgccg ccgacaccat cgacgccacc acgcggttgg 2400
tcctgcgctc catctccgag cgcgcggcgg tcgaccgcat cagcgagagc tttggccgca 2460
gcgcacaggt catgcacgac ccctttgggg ggcagccgtt tcccgccgcg aatagcccct 2520
gggccccggt gctggcgggc caaggagggc cctttgacgc cgagaccaga cgggtctcct 2580
gggaaacctt ggtcgcccac ggcccgagcc tctatcgcac ttttgccggc aatcctcggg 2640
ccgcatcgac cgccaaggcc atgcgcgact gcgtgctgcg ccaagaaaat ttcatcgagg 2700
cgctggcctc cgccgacgag acgctggcgt ggtgcaagat gtgcatccac cacaacctgc 2760
cgctgcgccc ccaggacccc attatcggga cggccgcggc tgtgctggat aacctcgcca 2820
cgcgcctgcg gccctttctc cagtgctacc tgaaggcgcg aggcctgtgc ggcctggacg 2880
aactgtgttc gcggcggcgt ctggcggaca ttaaggacat tgcatccttc gtgtttgtca 2940
ttctggccag gctcgccaac cgcgtcgagc gtggcgtcgc ggagatcgac tacgcgaccc 3000
ttggtgtcgg ggtcggagag aagatgcatt tctacctccc cggggcctgc atggcgggcc 3060
tgatcgaaat cctagacacg caccgccagg agtgttcgag tcgtgtctgc gagttgacgg 3120
ccagtcacat cgtcgccccc ccgtacgtgc acggcaaata tttttattgc aactccctgt 3180
tttag 3185
<210> 574
<211> 3670
<212> DNA
<213> 单纯疱疹病毒
<400> 574
atgtcgggcg tcgggggaga gggagttccc tctgcgcttg cgattctagc ctcgtggggc 60
tggacgttcg acacgccaaa ccacgagtcg gggatatcgc cagatacgac tcccgcagat 120
tccattcggg gtgccgctgt ggcctcacct gaccaacctt tacacggggg cccggaacgg 180
gaggccacag cgccgtcttt ctccccaacg cgcgcggatg acggcccgcc ctgtaccgac 240
gggccctacg tgacgtttga taccctgttt atggtgtcgt cgatcgacga attagggcgt 300
cgccagctca cggacaccat ccgcaaggac ctgcggttgt cgctggccaa gtttagcatt 360
gcgtgcacca agacctcctc gttttcggga aacgccccgc gccaccacag acgcggggcg 420
ttccagcgcg gcacgcgggc gccgcgcagc aacaaaagcc tccagatgtt tgtgttgtgc 480
aaacgcgccc acgccgctcg agtgcgagag cagcttcggg tcgttattca gtcccgcaag 540
ccgcgcaagt attacacgcg atcttcggac gggcggctct gccccgccgt ccccgtgttc 600
gtccacgagt tcgtctcgtc cgagccaatg cgcctccacc gagataacgt catgctggcc 660
tcgggggccg agtaaccgcc cccccgcgcc accctcactg cccgtcgcgc gtgtttgatg 720
ttaataaata acgcataaat ttggctggtt gtttgttgtc tttaatggac cgcccgcagg 780
gggggtggca tttcagtgtc gggtgacgag cgcgatccgg ccgggagagg ctccggtgcc 840
cgtcagtggg cagagcgcac atcgcccaca gtccccgaga agttgggggg aggggtcggc 900
aattgaaccg gtgcctagag aaggtggcgc ggggtaaact gggaaagtga tgtcgtgtac 960
tggctccgcc tttttcccga gggtggggga gaaccgtata taagtgcagt agtcgccgtg 1020
aacgttcttt ttcgcaacgg gtttgccgcc agaacacagg taagtgccgt gtgtggttcc 1080
cgcgggcctg gcctctttac gggttatggc ccttgcgtgc cttgaattac ttccacgccc 1140
ctggctgcag tacgtgattc ttgatcccga gcttcgggtt ggaagtgggt gggagagttc 1200
gaggccttgc gcttaaggag ccccttcgcc tcgtgcttga gttgaggcct ggcttgggcg 1260
ctggggccgc cgcgtgcgaa tctggtggca ccttcgcgcc tgtctcgctg ctttcgataa 1320
gtctctagcc atttaaaatt tttgatgacc tgctgcgacg ctttttttct ggcaagatag 1380
tcttgtaaat gcgggccaag atctgcacac tggtatttcg gtttttgggg ccgcgggcgg 1440
cgacggggcc cgtgcgtccc agcgcacatg ttcggcgagg cggggcctgc gagcgcggcc 1500
accgagaatc ggacgggggt agtctcaagc tggccggcct gctctggtgc ctggcctcgc 1560
gccgccgtgt atcgccccgc cctgggcggc aaggctggcc cggtcggcac cagttgcgtg 1620
agcggaaaga tggccgcttc ccggccctgc tgcagggagc tcaaaatgga ggacgcggcg 1680
ctcgggagag cgggcgggtg agtcacccac acaaaggaaa agggcctttc cgtcctcagc 1740
cgtcgcttca tgtgactcca cggagtaccg ggcgccgtcc aggcacctcg attagttctc 1800
gagcttttgg agtacgtcgt ctttaggttg gggggagggg ttttatgcga tggagtttcc 1860
ccacactgag tgggtggaga ctgaagttag gccagcttgg cacttgatgt aattctcctt 1920
ggaatttgcc ctttttgagt ttggatcttg gttcattctc aagcctcaga cagtggttca 1980
aagttttttt cttccatttc aggtgtcgtg agctagcatg tacaggatgc aactcctgtc 2040
ttgcattgca ctaagtcttg cacttgtcac gaattcgata tcgacagccc acccctctcc 2100
tagcccaaga tccgccggcc agttcgccat ggttagatct cccccatgcc catcatgccc 2160
agcacctgag ttcctggggg gaccatcagt cttcctgttc cccccaaaac ccaaggacac 2220
tctcatgatc tcccggaccc ctgaggtcac gtgcgtggtg gtggacgtga gccaggaaga 2280
ccccgaggtc cagttcaact ggtacgtgga tggcgtggag gtgcataatg ccaagacaaa 2340
gccgcgggag gagcagttca acagcacgta ccgtgtggtc agcgtcctca ccgtcctgca 2400
ccaggactgg ctgaacggca aggagtacaa gtgcaaggtc tccaacaaag gcctcccgtc 2460
ctccatcgag aaaaccatct ccaaagccaa agggcagccc cgagagccac aggtgtacac 2520
cctgccccca tcccaggagg agatgaccaa gaaccaggtc agcctgacct gcctggtcaa 2580
aggcttctac cccagcgaca tcgccgtgga gtgggagagc aatgggcagc cggagaacaa 2640
ctacaagacc acgcctcccg tgctggactc cgacggctcc ttcttcctct acagcaggct 2700
aaccgtggac aagagcaggt ggcaggaggg gaatgtcttc tcatgctccg tgatgcatga 2760
ggctctgcac aaccactaca cacagaagag cctctccctg tctccgggta aatgagtgga 2820
tccaccggat ctagataact gatcataatc agccatacca catttgtaga ggttttactt 2880
gctttaaaaa acctcccaca cctccccctg aacctgaaac ataaaatgaa tgcaattgtt 2940
gttgttaact tgtttattgc agcttataat ggttacaaat aaagcaatag catcacaaat 3000
ttcacaaata aagcattttt ttcactgcat tctagttgtg gtttgtccaa actcatcaat 3060
gtatcttatc ctaggacccc aaaagtttgt ctgcgtattc cagggcgggg ctcagttgaa 3120
tctcccgcag cacctctacc agcaggtccg cggtgggctg gagaaactcg gccgtcccgg 3180
ggcaggcggt cgtcgggggt ggaggcgcgg cgcccacccc gtgtgccgcg cctggcgtct 3240
cctctggggg cgacccgtaa atggttgcag tgatgtaaat ggtgtccgcg gtccagacca 3300
cggtcaaaat gccggccgtg gcgctccggg cgctttcgcc gcgcgaggag ctgacccagg 3360
agtcgaacgg atacgcgtac atatgggcgt cccacccgcg ttcgagcttc tggttgctgt 3420
cccggcctat aaagcggtag gcacaaaatt cggcgcgaca gtcgataatc accaacagcc 3480
caatgggggt gtgctggata acaacgcctc cgcgcggcag gcggtcctgg cgctcccggc 3540
cccgtaccat gatcgcgcgg gtgccgtact caaaaacatg caccacctgc gcggcgtcgg 3600
gcagtgcgct ggtcagcgag gccctggcgt ggcataggct atacgcgatg gtcgtctgtg 3660
gattggacat 3670
<210> 575
<211> 6903
<212> DNA
<213> 单纯疱疹病毒
<400> 575
ttagaggcgc cgggagtggg gtcgtcggcg tctgcttttt gtggcggcgt cccgtcgcgg 60
ggtggggtcc gacgtggcga tgatgggcgg cggcgtggtg aggggcttcg gctgcaggcc 120
cgcttcatcg tccggcggca gaaccggggt ccgtccagac gttccgttgg taggtcccaa 180
atcctgtcgc cctacacagc ggcgggtgcg cgaatagtca aagttcacac acccagcctt 240
cacaggtgtg tggctggcgg cctgcttgcg actgtccagc gcctggcgta tctctttata 300
aagggccaag cgcgtttctg tttcctgggt gttggcagga aacgcggggt aactcaagtc 360
ctccaaaaaa cccgccacaa ataaaaaggg gttaacccaa tatgccttct gggcatgcct 420
atcccacaag accgtgtcca atccgggaca gtgataacgc aaaaatatac cgtctatcaa 480
agcatagttt atagccgagg gggtctcgta acgccaatca agatcgtcag acgggagcgg 540
cacacaaggc acctttaata tatcccccac ctctcgagcc acccgactcc gaataacata 600
ttcggttgaa gacaagcccc cccgcacaca caaaacccca acggcaataa gcccgaccca 660
acccaaaatc cccatagcgc ctagggtcgg cacccacaga aacctacagt ccccaagtgt 720
ttgcccagta acacaaccac gacgtcgtgc cacacaagcc ccgtatcccc gttcccgcgc 780
ttttcgttgg tttatataca cattgattat tgactagtta ttaatagtaa tcaattacgg 840
ggtcattagt tcatagccca tatatggagt tccgcgttac ataacttacg gtaaatggcc 900
cgcctggctg accgcccaac gacccccgcc cattgacgtc aataatgacg tatgttccca 960
tagtaacgcc aatagggact ttccattgac gtcaatgggt ggagtattta cggtaaactg 1020
cccacttggc agtacatcaa gtgtatcata tgccaagtac gccccctatt gacgtcaatg 1080
acggtaaatg gcccgcctgg cattatgccc agtacatgac cttatgggac tttcctactt 1140
ggcagtacat ctacgtatta gtcatcgcta ttaccatggt gatgcggttt tggcagtaca 1200
tcaatgggcg tggatagcgg tttgactcac ggggatttcc aagtctccac cccattgacg 1260
tcaatgggag tttgttttgg caccaaaatc aacgggactt tccaaaatgt cgtaacaact 1320
ccgccccatt gacgcaaatg ggcggtaggc gtgtacggtg ggaggtctat ataagcagag 1380
ctctctggct aactagagaa cccactgctt actggcttat cgaaattaat acgactcact 1440
atagggagac ccaagctggc tagcgtttaa acttaagctt ggtaccgagc tcggatccac 1500
tagtccagtg tggtggaatt cgccaccatg tgccatcagc agctggtcat ctcatggttc 1560
tccctggtgt ttctggcctc acctctggtc gcaatctggg aactgaaaaa ggatgtgtac 1620
gtggtggagc tggactggta tcccgatgcc cctggcgaga tggtggtgct gacctgcgac 1680
acacccgagg aggatggcat cacctggaca ctggatcaga gctccgaggt gctgggaagc 1740
ggcaagaccc tgacaatcca ggtgaaggag ttcggcgacg ccggccagta cacctgtcac 1800
aagggaggag aggtgctgag ccactccctg ctgctgctgc acaagaagga ggatggcatc 1860
tggtccacag acatcctgaa ggatcagaag gagccaaaga acaagacctt cctgcggtgc 1920
gaggccaaga attatagcgg ccggttcacc tgttggtggc tgaccacaat ctccaccgat 1980
ctgacatttt ctgtgaagtc tagcagggga tcctctgacc cacagggagt gacatgcgga 2040
gcagccaccc tgagcgccga gagggtgcgc ggcgataaca aggagtacga gtattccgtg 2100
gagtgccagg aggactctgc ctgtccagca gcagaggagt ccctgcctat cgaagtgatg 2160
gtggatgccg tgcacaagct gaagtacgag aattatacca gctccttctt tatccgggac 2220
atcatcaagc ccgatccccc taagaacctg cagctgaagc ctctgaagaa tagcagacag 2280
gtggaggtgt cctgggagta ccctgacacc tggagcacac cacactccta tttctctctg 2340
accttttgcg tgcaggtgca gggcaagtcc aagcgggaga agaaggacag agtgttcacc 2400
gataagacat ctgccaccgt gatctgtaga aagaacgcct ctatcagcgt gagggcccag 2460
gaccgctact attctagctc ctggtccgag tgggcctctg tgccttgcag cggcggagga 2520
ggaggaggat ctatgtgccc agcaaggagc ctgctgctgg tggccacact ggtgctgctg 2580
gatcacctgt ccctggcaag gaatctgcca gtggcaaccc ctgacccagg catgttcccc 2640
tgcctgcacc acagccagaa cctgctgagg gccgtgtcca atatgctgca gaaggcccgc 2700
cagacactgg agttttaccc ttgtaccagc gaggagatcg accacgagga catcacaaag 2760
gataagacct ccacagtgga ggcctgcctg ccactggagc tgaccaagaa cgagtcctgt 2820
ctgaacagcc gggagacaag cttcatcacc aacggctcct gcctggcctc tagaaagaca 2880
agctttatga tggccctgtg cctgtctagc atctacgagg acctgaagat gtatcaggtg 2940
gagttcaaga ccatgaacgc caagctgctg atggacccca agaggcagat ctttctggat 3000
cagaatatgc tggccgtgat cgacgagctg atgcaggccc tgaacttcaa tagcgagaca 3060
gtgcctcaga agtcctctct ggaggagcca gatttctaca agaccaagat caagctgtgc 3120
atcctgctgc acgcctttcg gatcagagcc gtgacaatcg accgcgtgat gtcctatctg 3180
aacgcctctg gaggaggagg aagcggagga ggaggatccg gcggcggcgg ctccggctct 3240
ggcgccacca acttctccct gctgaagcag gcaggcgacg tggaggagaa tccaggacct 3300
atgcggatct ctaagcctca cctgagaagc atctccatcc agtgctacct gtgcctgctg 3360
ctgaacagcc actttctgac agaggccggc atccacgtgt tcatcctggg ctgttttagc 3420
gccggcctgc caaagaccga ggcaaactgg gtgaatgtga tctctgacct gaagaagatc 3480
gaggatctga tccagagcat gcacatcgat gccacactgt ataccgagtc tgacgtgcac 3540
cctagctgca aggtgaccgc catgaagtgt ttcctgctgg agctgcaggt catcagcctg 3600
gagtccggcg acgcaagcat ccacgataca gtggagaacc tgatcatcct ggccaacaat 3660
agcctgagct ccaacggcaa tgtgaccgag tccggctgca aggagtgtga ggagctggag 3720
gagaagaaca tcaaggagtt cctgcagagc tttgtgcaca tcgtgcagat gttcatcaat 3780
acatccggag gaggaggatc aggcggagga ggaagcggcg gcggcggctc tggcagcggc 3840
gccaccaact tttccctgct gaagcaggcc ggcgatgtgg aagaaaatcc aggaccaatg 3900
gcaccaagga gagcaagggg atgcagaacc ctgggcctgc ctgccctgtt attactgctg 3960
ctgctgaggc caccagcaac aaggggaatc acctgtcctc cacccatgag cgtggagcac 4020
gccgacatct gggtgaagtc ctactctctg tattctaggg agcggtacat ctgcaacagc 4080
ggctttaaga ggaaggccgg cacatctagc ctgaccgagt gcgtgctgaa caaggccacc 4140
aatgtggccc actggaccac accttccctg aagtgcatca gggatccagc cctggtgcac 4200
cagcgccccg cacctccaag cacagtgacc acagcaggag tgacccctca gccagagagc 4260
ctgtcccctt ctggcaagga gccagcagca tcctctccaa gctccaacaa tacagcagca 4320
accacagcag caatcgtgcc aggctcccag ctgatgccaa gcaagtcccc ctctaccggc 4380
accacagaga tctctagcca cgagtcctct cacggcacac caagccagac cacagccaag 4440
aattgggagc tgaccgcaag cgcctcccac cagccacctg gcgtgtaccc acagggacac 4500
tccgacacca cagtggccat ctctaccagc acagtgctgc tgtgcggcct gtctgccgtg 4560
agcctgctgg cctgttatct gaagtccagg cagaccccac cactggcatc tgtggagatg 4620
gaggccatgg aggccctgcc cgtcacatgg gggactagta gtagagacga ggatctggaa 4680
aactgtagtc accatctgta agatatccat cacactggcg gccgctcgag catgcatcta 4740
gagggcccta ttctatagtg tcacctaaat gctagagctc gctgatcagc ctcgactgtg 4800
ccttctagtt gccagccatc tgttgtttgc ccctcccccg tgccttcctt gaccctggaa 4860
ggtgccactc ccactgtcct ttcctaataa aatgaggaaa ttgcatcgca ttgtctgagt 4920
aggtgtcatt ctattctggg gggtggggtg gggcaggaca gcaaggggga ggattgggaa 4980
gacaatagca ggcatgctgg ggatgcggtg ggctctatgg ggatccacta gttctagagc 5040
ggccgccgca cataaaggcc cggcgcgacc gacgcccgca gacggcgccg gccacgaacg 5100
acgggagcgg ctgcggagca cgcggaccgg gagcgggact cgcagagggc cgtcggagcg 5160
gacggcgtcg gcatcgcgac gccccggctc gggatcggga tcgcatcgga aagggacacg 5220
cggaaagacc cacccacccc acccacgaaa cacaggggac gcaccccggg ggcctccgac 5280
gacagaaacc caccggtccg cctttgtgca cgggtaagca ccttgggtgg gcggaggagg 5340
ggggacgcgg gggcggagga gggggctcac ccgcgttcgt gccttcccgc aggaggaacg 5400
tcctcgtcga ggcgaccggc ggcgaccgtt gcgtggaccg cttcctgctc gtcggggcga 5460
ccggcggcga ccgttgcgtg gaccgcttcc tgctcgtcgg gcgggggagc atgtcgtggg 5520
ccctggaaat ggcggacacc ttcctggaca acatgcgggt tgggcccagg acgtacgccg 5580
acgtacgcga tgagatcaat aaaagggggc gtgaggaccg ggaggcggcc aaaaccgccg 5640
tgcacgaccc ggagcgtcct ctgctgcgct ctcccgggct gctgcccaaa atcgccccca 5700
acgcatcctt gggtgtggca catcgaagaa ccggcgggac cgtgaccgac agtccccgta 5760
atccggtaac ccgttgagtc ccgggtacga ccatcgccca agtttctggg cggagggtgg 5820
ttccccccgt ggctctcgag atgagccaga cccaaccccc ggccccagtt gggccgggcg 5880
acccagatgt ttacttaaaa ggcgtgccgt ccgccggcat gcaccccaga ggtgttcacg 5940
cacctcgagg acacccgcgc atgatctccg gacccccgca acggggtgat aatgatcaag 6000
cggcggggca atgtggagat tcgggtctac tacgagtcgg tgcggacact acgatctcga 6060
agccatctga agccgtccga ccgccaacaa tccccaggac accgcgtgtt ccccgggagc 6120
cccgggttcc gcgaccaccc cgagaaccta gggaacccag agtaccgcga gctcccagag 6180
accccagggt accgcgtgac cccagggatc cacgacaacc ccgggagccc cggcctcccc 6240
gggagccccg gaccccacgc accccccgcg aaccacgtac ggctcgcggg tctgtatagc 6300
ccgggcaagt atgcccccct ggcgagccca gaccccttct ccccacaaga tggagcgtac 6360
gctcgggccc gcgtagggct ccacaccgcg gttcgcgtcc cgcccaccgg aagcccaacc 6420
cacacgcact tgcggcatga cccgggcgat gagccaacct cggatgactc agggctctac 6480
cctctggacg cccgggcgct tgcgcacctg gtgatgttgc ccgcggacca ccgggccttc 6540
tttcgaaccg tggtcgaggt gtctcgcatg tgcgctgcaa acgtgcgcga tcccccgccc 6600
ccggctacag gggccatgtt gggccgccac gcgcggctgg tccacaccca gtggctccgg 6660
gccaaccaag agacgtcgcc cctgtggccc tggcggacgg cggccattaa ctttatcacc 6720
accatggccc cccgcgtcca aacccaccga cacatgcacg acctgttgat ggcctgtgct 6780
ttctggtgct gtctgacaca cgcatcgacg tgttcgtacg cggggctgta ctcgacccac 6840
tgcctgcatc tgtttggtgc gtttgggtgt ggggacccgg ccctaacccc acccctgtgc 6900
tag 6903
<210> 576
<211> 5777
<212> DNA
<213> 单纯疱疹病毒
<400> 576
ttagatgcgc cgggagtggg gtcgtcggcg tctgcttttt gcggcggcgt cccgtcgcgg 60
ggtggggtcc aacgtggcga tgatgggcgg cggcgtggtg aggggcttcg gctgcaggcc 120
cgcttcatcg tccggcggca gaaccggggt ccgtccagac gttccgttgg taggtcccaa 180
atcctgtcgc cctacacagc ggcgggtgcg cgaatagtca aagttcacac acccagcctt 240
cacaggtgtg tggctggcgg cctgcttgcg actgtccagc gcctggcgta tctctttata 300
aagggccaag cgcgtttctg tttcctgggt gttggcagga aacgcggggt gactcaagtc 360
ctccaaaaaa cccgccacaa ataaaaaggg gttaacccaa tatgccttct gggcatgcct 420
atcccacaag accgtgtcca atccgggaca gtgataacgc aaaaatatac cgtctatcaa 480
agcatagttt atagccgagg gggtctcgta acgccaatca agatcgtcag acgggagcgg 540
cacacaaggc acctttaata tatcccccac ctctcgagcc acccgactcc gaataacata 600
ttcggttgaa gacaagcccc cccgcacaca caaaacccca acggcaataa gcccgaccca 660
acccaaaatc cccatagcgc ctagggtcgg cacccacaga aacctacagt ccccaagtgt 720
ttgcccagta acacaaccac gacgtcgtgc cacacaagcc ccgtatcccc gttcccgcgc 780
ttttcgttgg tttatataca cattgattat tgactagtta ttaatagtaa tcaattacgg 840
ggtcattagt tcatagccca tatatggagt tccgcgttac ataacttacg gtaaatggcc 900
cgcctggctg accgcccaac gacccccgcc cattgacgtc aataatgacg tatgttccca 960
tagtaacgcc aatagggact ttccattgac gtcaatgggt ggagtattta cggtaaactg 1020
cccacttggc agtacatcaa gtgtatcata tgccaagtac gccccctatt gacgtcaatg 1080
acggtaaatg gcccgcctgg cattatgccc agtacatgac cttatgggac tttcctactt 1140
ggcagtacat ctacgtatta gtcatcgcta ttaccatggt gatgcggttt tggcagtaca 1200
tcaatgggcg tggatagcgg tttgactcac ggggatttcc aagtctccac cccattgacg 1260
tcaatgggag tttgttttgg caccaaaatc aacgggactt tccaaaatgt cgtaacaact 1320
ccgccccatt gacgcaaatg ggcggtaggc gtgtacggtg ggaggtctat ataagcagag 1380
ctctctggct aactagagaa cccactgctt actggcttat cgaaattaat acgactcact 1440
atagggagac ccaagctggc tagcgtttaa acttaagctt ggtaccgagc tcggatccac 1500
tagtccagtg tggtggaatt cgccaccatg tgccatcagc agctggtcat ctcatggttc 1560
tccctggtgt ttctggcctc acctctggtc gcaatctggg aactgaaaaa ggatgtgtac 1620
gtggtggagc tggactggta tcccgatgcc cctggcgaga tggtggtgct gacctgcgac 1680
acacccgagg aggatggcat cacctggaca ctggatcaga gctccgaggt gctgggaagc 1740
ggcaagaccc tgacaatcca ggtgaaggag ttcggcgacg ccggccagta cacctgtcac 1800
aagggaggag aggtgctgag ccactccctg ctgctgctgc acaagaagga ggatggcatc 1860
tggtccacag acatcctgaa ggatcagaag gagccaaaga acaagacctt cctgcggtgc 1920
gaggccaaga attatagcgg ccggttcacc tgttggtggc tgaccacaat ctccaccgat 1980
ctgacatttt ctgtgaagtc tagcagggga tcctctgacc cacagggagt gacatgcgga 2040
gcagccaccc tgagcgccga gagggtgcgc ggcgataaca aggagtacga gtattccgtg 2100
gagtgccagg aggactctgc ctgtccagca gcagaggagt ccctgcctat cgaagtgatg 2160
gtggatgccg tgcacaagct gaagtacgag aattatacca gctccttctt tatccgggac 2220
atcatcaagc ccgatccccc taagaacctg cagctgaagc ctctgaagaa tagcagacag 2280
gtggaggtgt cctgggagta ccctgacacc tggagcacac cacactccta tttctctctg 2340
accttttgcg tgcaggtgca gggcaagtcc aagcgggaga agaaggacag agtgttcacc 2400
gataagacat ctgccaccgt gatctgtaga aagaacgcct ctatcagcgt gagggcccag 2460
gaccgctact attctagctc ctggtccgag tgggcctctg tgccttgcag cggcggagga 2520
ggaggaggat ctatgtgccc agcaaggagc ctgctgctgg tggccacact ggtgctgctg 2580
gatcacctgt ccctggcaag gaatctgcca gtggcaaccc ctgacccagg catgttcccc 2640
tgcctgcacc acagccagaa cctgctgagg gccgtgtcca atatgctgca gaaggcccgc 2700
cagacactgg agttttaccc ttgtaccagc gaggagatcg accacgagga catcacaaag 2760
gataagacct ccacagtgga ggcctgcctg ccactggagc tgaccaagaa cgagtcctgt 2820
ctgaacagcc gggagacaag cttcatcacc aacggctcct gcctggcctc tagaaagaca 2880
agctttatga tggccctgtg cctgtctagc atctacgagg acctgaagat gtatcaggtg 2940
gagttcaaga ccatgaacgc caagctgctg atggacccca agaggcagat ctttctggat 3000
cagaatatgc tggccgtgat cgacgagctg atgcaggccc tgaacttcaa tagcgagaca 3060
gtgcctcaga agtcctctct ggaggagcca gatttctaca agaccaagat caagctgtgc 3120
atcctgctgc acgcctttcg gatcagagcc gtgacaatcg accgcgtgat gtcctatctg 3180
aacgcctctg gaggaggagg aagcggagga ggaggatccg gcggcggcgg ctccggctct 3240
ggcgccacca acttctccct gctgaagcag gcaggcgacg tggaggagaa tccaggacct 3300
atgcggatct ctaagcctca cctgagaagc atctccatcc agtgctacct gtgcctgctg 3360
ctgaacagcc actttctgac agaggccggc atccacgtgt tcatcctggg ctgttttagc 3420
gccggcctgc caaagaccga ggcaaactgg gtgaatgtga tctctgacct gaagaagatc 3480
gaggatctga tccagagcat gcacatcgat gccacactgt ataccgagtc tgacgtgcac 3540
cctagctgca aggtgaccgc catgaagtgt ttcctgctgg agctgcaggt catcagcctg 3600
gagtccggcg acgcaagcat ccacgataca gtggagaacc tgatcatcct ggccaacaat 3660
agcctgagct ccaacggcaa tgtgaccgag tccggctgca aggagtgtga ggagctggag 3720
gagaagaaca tcaaggagtt cctgcagagc tttgtgcaca tcgtgcagat gttcatcaat 3780
acatccggag gaggaggatc aggcggagga ggaagcggcg gcggcggctc tggcagcggc 3840
gccaccaact tttccctgct gaagcaggcc ggcgatgtgg aagaaaatcc aggaccaatg 3900
gcaccaagga gagcaagggg atgcagaacc ctgggcctgc ctgccctgtt attactgctg 3960
ctgctgaggc caccagcaac aaggggaatc acctgtcctc cacccatgag cgtggagcac 4020
gccgacatct gggtgaagtc ctactctctg tattctaggg agcggtacat ctgcaacagc 4080
ggctttaaga ggaaggccgg cacatctagc ctgaccgagt gcgtgctgaa caaggccacc 4140
aatgtggccc actggaccac accttccctg aagtgcatca gggatccagc cctggtgcac 4200
cagcgccccg cacctccaag cacagtgacc acagcaggag tgacccctca gccagagagc 4260
ctgtcccctt ctggcaagga gccagcagca tcctctccaa gctccaacaa tacagcagca 4320
accacagcag caatcgtgcc aggctcccag ctgatgccaa gcaagtcccc ctctaccggc 4380
accacagaga tctctagcca cgagtcctct cacggcacac caagccagac cacagccaag 4440
aattgggagc tgaccgcaag cgcctcccac cagccacctg gcgtgtaccc acagggacac 4500
tccgacacca cagtggccat ctctaccagc acagtgctgc tgtgcggcct gtctgccgtg 4560
agcctgctgg cctgttatct gaagtccagg cagaccccac cactggcatc tgtggagatg 4620
gaggccatgg aggccctgcc cgtcacatgg gggactagta gtagagacga ggatctggaa 4680
aactgtagtc accatctgta agatatccat cacactggcg gccgctcgag catgcatcta 4740
gagggcccta ttctatagtg tcacctaaat gctagagctc gctgatcagc ctcgactgtg 4800
ccttctagtt gccagccatc tgttgtttgc ccctcccccg tgccttcctt gaccctggaa 4860
ggtgccactc ccactgtcct ttcctaataa aatgaggaaa ttgcatcgca ttgtctgagt 4920
aggtgtcatt ctattctggg gggtggggtg gggcaggaca gcaaggggga ggattgggaa 4980
gacaatagca ggcatgctgg ggatgcggtg ggctctatgg ggatccacta gttctagagc 5040
ggccgccgca cataaaggcc cggcgcgacc gacgcccgca gacggcgccg gccacgaacg 5100
acgggagcgg ctgcggagca cgcggaccgg gagcgggact cgcagagggc cgtcggagcg 5160
gacggcgtcg gcatcgcgac gccccggctc gggatcggga tcgcatcgga aagggacacg 5220
cggaaagacc cacccacccc acccacgaaa cacaggggac gcaccccggg ggcctccgac 5280
gacagaaacc caccggtccg cctttgtgca cgggtaagca ccttgggtgg gcggaggagg 5340
ggggacgcgg gggcggagga gggggctcac ccgcgttcgt gccttcccgc aggaggaacg 5400
tcctcgtcga ggcgaccggc ggcgaccgtt gcgtggaccg cttcctgctc gtcggggcga 5460
ccggcggcga ccgttgcgtg gaccgcttcc tgctcgtcgg gcgggggagc atgtcgtggg 5520
ccctggaaat ggcggacacc ttcctggaca acatgcgggt tgggcccagg acgtacgccg 5580
acgtacgcga tgagatcaat aaaagggggc gtgaggaccg ggaggcggcc aaaaccgccg 5640
tgcacgaccc ggagcgtcct ctgctgcgct ctcccgggct gctgcccaaa atcgccccca 5700
acgcatcctt gggtgtggca catcgaagaa ccggcgggac cgtgaccgac agtccccgta 5760
atccggtaac ccgttga 5777
<210> 577
<211> 1057
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 577
Met Cys His Gln Gln Leu Val Ile Ser Trp Phe Ser Leu Val Phe Leu
1 5 10 15
Ala Ser Pro Leu Val Ala Ile Trp Glu Leu Lys Lys Asp Val Tyr Val
20 25 30
Val Glu Leu Asp Trp Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu
35 40 45
Thr Cys Asp Thr Pro Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln
50 55 60
Ser Ser Glu Val Leu Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys
65 70 75 80
Glu Phe Gly Asp Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val
85 90 95
Leu Ser His Ser Leu Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp
100 105 110
Ser Thr Asp Ile Leu Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe
115 120 125
Leu Arg Cys Glu Ala Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp
130 135 140
Leu Thr Thr Ile Ser Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg
145 150 155 160
Gly Ser Ser Asp Pro Gln Gly Val Thr Cys Gly Ala Ala Thr Leu Ser
165 170 175
Ala Glu Arg Val Arg Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu
180 185 190
Cys Gln Glu Asp Ser Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile
195 200 205
Glu Val Met Val Asp Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr
210 215 220
Ser Ser Phe Phe Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn
225 230 235 240
Leu Gln Leu Lys Pro Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp
245 250 255
Glu Tyr Pro Asp Thr Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr
260 265 270
Phe Cys Val Gln Val Gln Gly Lys Ser Lys Arg Glu Lys Lys Asp Arg
275 280 285
Val Phe Thr Asp Lys Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala
290 295 300
Ser Ile Ser Val Arg Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser
305 310 315 320
Glu Trp Ala Ser Val Pro Cys Ser Gly Gly Gly Gly Gly Gly Ser Met
325 330 335
Cys Pro Ala Arg Ser Leu Leu Leu Val Ala Thr Leu Val Leu Leu Asp
340 345 350
His Leu Ser Leu Ala Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly
355 360 365
Met Phe Pro Cys Leu His His Ser Gln Asn Leu Leu Arg Ala Val Ser
370 375 380
Asn Met Leu Gln Lys Ala Arg Gln Thr Leu Glu Phe Tyr Pro Cys Thr
385 390 395 400
Ser Glu Glu Ile Asp His Glu Asp Ile Thr Lys Asp Lys Thr Ser Thr
405 410 415
Val Glu Ala Cys Leu Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys Leu
420 425 430
Asn Ser Arg Glu Thr Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala Ser
435 440 445
Arg Lys Thr Ser Phe Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu
450 455 460
Asp Leu Lys Met Tyr Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu
465 470 475 480
Leu Met Asp Pro Lys Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala
485 490 495
Val Ile Asp Glu Leu Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val
500 505 510
Pro Gln Lys Ser Ser Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys Ile
515 520 525
Lys Leu Cys Ile Leu Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile
530 535 540
Asp Arg Val Met Ser Tyr Leu Asn Ala Ser Gly Gly Gly Gly Ser Gly
545 550 555 560
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Ser Gly Ala Thr Asn Phe
565 570 575
Ser Leu Leu Lys Gln Ala Gly Asp Val Glu Glu Asn Pro Gly Pro Met
580 585 590
Arg Ile Ser Lys Pro His Leu Arg Ser Ile Ser Ile Gln Cys Tyr Leu
595 600 605
Cys Leu Leu Leu Asn Ser His Phe Leu Thr Glu Ala Gly Ile His Val
610 615 620
Phe Ile Leu Gly Cys Phe Ser Ala Gly Leu Pro Lys Thr Glu Ala Asn
625 630 635 640
Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile Gln
645 650 655
Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His Pro
660 665 670
Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln Val
675 680 685
Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu Asn
690 695 700
Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val Thr
705 710 715 720
Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile Lys
725 730 735
Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn Thr
740 745 750
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
755 760 765
Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln Ala Gly Asp Val
770 775 780
Glu Glu Asn Pro Gly Pro Met Ala Pro Arg Arg Ala Arg Gly Cys Arg
785 790 795 800
Thr Leu Gly Leu Pro Ala Leu Leu Leu Leu Leu Leu Leu Arg Pro Pro
805 810 815
Ala Thr Arg Gly Ile Thr Cys Pro Pro Pro Met Ser Val Glu His Ala
820 825 830
Asp Ile Trp Val Lys Ser Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile
835 840 845
Cys Asn Ser Gly Phe Lys Arg Lys Ala Gly Thr Ser Ser Leu Thr Glu
850 855 860
Cys Val Leu Asn Lys Ala Thr Asn Val Ala His Trp Thr Thr Pro Ser
865 870 875 880
Leu Lys Cys Ile Arg Asp Pro Ala Leu Val His Gln Arg Pro Ala Pro
885 890 895
Pro Ser Thr Val Thr Thr Ala Gly Val Thr Pro Gln Pro Glu Ser Leu
900 905 910
Ser Pro Ser Gly Lys Glu Pro Ala Ala Ser Ser Pro Ser Ser Asn Asn
915 920 925
Thr Ala Ala Thr Thr Ala Ala Ile Val Pro Gly Ser Gln Leu Met Pro
930 935 940
Ser Lys Ser Pro Ser Thr Gly Thr Thr Glu Ile Ser Ser His Glu Ser
945 950 955 960
Ser His Gly Thr Pro Ser Gln Thr Thr Ala Lys Asn Trp Glu Leu Thr
965 970 975
Ala Ser Ala Ser His Gln Pro Pro Gly Val Tyr Pro Gln Gly His Ser
980 985 990
Asp Thr Thr Val Ala Ile Ser Thr Ser Thr Val Leu Leu Cys Gly Leu
995 1000 1005
Ser Ala Val Ser Leu Leu Ala Cys Tyr Leu Lys Ser Arg Gln Thr
1010 1015 1020
Pro Pro Leu Ala Ser Val Glu Met Glu Ala Met Glu Ala Leu Pro
1025 1030 1035
Val Thr Trp Gly Thr Ser Ser Arg Asp Glu Asp Leu Glu Asn Cys
1040 1045 1050
Ser His His Leu
1055
<210> 578
<211> 554
<212> PRT
<213> 智人
<400> 578
Met Cys His Gln Gln Leu Val Ile Ser Trp Phe Ser Leu Val Phe Leu
1 5 10 15
Ala Ser Pro Leu Val Ala Ile Trp Glu Leu Lys Lys Asp Val Tyr Val
20 25 30
Val Glu Leu Asp Trp Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu
35 40 45
Thr Cys Asp Thr Pro Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln
50 55 60
Ser Ser Glu Val Leu Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys
65 70 75 80
Glu Phe Gly Asp Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val
85 90 95
Leu Ser His Ser Leu Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp
100 105 110
Ser Thr Asp Ile Leu Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe
115 120 125
Leu Arg Cys Glu Ala Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp
130 135 140
Leu Thr Thr Ile Ser Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg
145 150 155 160
Gly Ser Ser Asp Pro Gln Gly Val Thr Cys Gly Ala Ala Thr Leu Ser
165 170 175
Ala Glu Arg Val Arg Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu
180 185 190
Cys Gln Glu Asp Ser Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile
195 200 205
Glu Val Met Val Asp Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr
210 215 220
Ser Ser Phe Phe Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn
225 230 235 240
Leu Gln Leu Lys Pro Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp
245 250 255
Glu Tyr Pro Asp Thr Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr
260 265 270
Phe Cys Val Gln Val Gln Gly Lys Ser Lys Arg Glu Lys Lys Asp Arg
275 280 285
Val Phe Thr Asp Lys Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala
290 295 300
Ser Ile Ser Val Arg Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser
305 310 315 320
Glu Trp Ala Ser Val Pro Cys Ser Gly Gly Gly Gly Gly Gly Ser Met
325 330 335
Cys Pro Ala Arg Ser Leu Leu Leu Val Ala Thr Leu Val Leu Leu Asp
340 345 350
His Leu Ser Leu Ala Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly
355 360 365
Met Phe Pro Cys Leu His His Ser Gln Asn Leu Leu Arg Ala Val Ser
370 375 380
Asn Met Leu Gln Lys Ala Arg Gln Thr Leu Glu Phe Tyr Pro Cys Thr
385 390 395 400
Ser Glu Glu Ile Asp His Glu Asp Ile Thr Lys Asp Lys Thr Ser Thr
405 410 415
Val Glu Ala Cys Leu Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys Leu
420 425 430
Asn Ser Arg Glu Thr Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala Ser
435 440 445
Arg Lys Thr Ser Phe Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu
450 455 460
Asp Leu Lys Met Tyr Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu
465 470 475 480
Leu Met Asp Pro Lys Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala
485 490 495
Val Ile Asp Glu Leu Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val
500 505 510
Pro Gln Lys Ser Ser Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys Ile
515 520 525
Lys Leu Cys Ile Leu Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile
530 535 540
Asp Arg Val Met Ser Tyr Leu Asn Ala Ser
545 550
<210> 579
<211> 162
<212> PRT
<213> 智人
<400> 579
Met Arg Ile Ser Lys Pro His Leu Arg Ser Ile Ser Ile Gln Cys Tyr
1 5 10 15
Leu Cys Leu Leu Leu Asn Ser His Phe Leu Thr Glu Ala Gly Ile His
20 25 30
Val Phe Ile Leu Gly Cys Phe Ser Ala Gly Leu Pro Lys Thr Glu Ala
35 40 45
Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile
50 55 60
Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His
65 70 75 80
Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln
85 90 95
Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu
100 105 110
Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val
115 120 125
Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile
130 135 140
Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn
145 150 155 160
Thr Ser
<210> 580
<211> 267
<212> PRT
<213> 智人
<400> 580
Met Ala Pro Arg Arg Ala Arg Gly Cys Arg Thr Leu Gly Leu Pro Ala
1 5 10 15
Leu Leu Leu Leu Leu Leu Leu Arg Pro Pro Ala Thr Arg Gly Ile Thr
20 25 30
Cys Pro Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val Lys Ser
35 40 45
Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly Phe Lys
50 55 60
Arg Lys Ala Gly Thr Ser Ser Leu Thr Glu Cys Val Leu Asn Lys Ala
65 70 75 80
Thr Asn Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys Ile Arg Asp
85 90 95
Pro Ala Leu Val His Gln Arg Pro Ala Pro Pro Ser Thr Val Thr Thr
100 105 110
Ala Gly Val Thr Pro Gln Pro Glu Ser Leu Ser Pro Ser Gly Lys Glu
115 120 125
Pro Ala Ala Ser Ser Pro Ser Ser Asn Asn Thr Ala Ala Thr Thr Ala
130 135 140
Ala Ile Val Pro Gly Ser Gln Leu Met Pro Ser Lys Ser Pro Ser Thr
145 150 155 160
Gly Thr Thr Glu Ile Ser Ser His Glu Ser Ser His Gly Thr Pro Ser
165 170 175
Gln Thr Thr Ala Lys Asn Trp Glu Leu Thr Ala Ser Ala Ser His Gln
180 185 190
Pro Pro Gly Val Tyr Pro Gln Gly His Ser Asp Thr Thr Val Ala Ile
195 200 205
Ser Thr Ser Thr Val Leu Leu Cys Gly Leu Ser Ala Val Ser Leu Leu
210 215 220
Ala Cys Tyr Leu Lys Ser Arg Gln Thr Pro Pro Leu Ala Ser Val Glu
225 230 235 240
Met Glu Ala Met Glu Ala Leu Pro Val Thr Trp Gly Thr Ser Ser Arg
245 250 255
Asp Glu Asp Leu Glu Asn Cys Ser His His Leu
260 265
<210> 581
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 581
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
1 5 10 15
Ser Gly
<210> 582
<211> 19
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 582
Ala Thr Asn Phe Ser Leu Leu Lys Gln Ala Gly Asp Val Glu Glu Asn
1 5 10 15
Pro Gly Pro
<210> 583
<211> 4
<212> DNA
<213> 单纯疱疹病毒
<400> 583
gagc
<210> 584
<211> 464
<212> DNA
<213> 单纯疱疹病毒
<400> 584
cgcacataaa ggcccggcgc gaccgacgcc cgcagacggc gccggccacg aacgacggga 60
gcggctgcgg agcacgcgga ccgggagcgg gactcgcaga gggccgtcgg agcggacggc 120
gtcggcatcg cgacgccccg gctcgggatc gggatcgcat cggaaaggga cacgcggaaa 180
gacccaccca ccccacccac gaaacacagg ggacgcaccc cgggggcctc cgacgacaga 240
aacccaccgg tccgcctttg tgcacgggta agcaccttgg gtgggcggag gaggggggac 300
gcgggggcgg aggagggggc tcacccgcgt tcgtgccttc ccgcaggagg aacgtcctcg 360
tcgaggcgac cggcggcgac cgttgcgtgg accgcttcct gctcgtcggg gcgaccggcg 420
gcgaccgttg cgtggaccgc ttcctgctcg tcgggcgggg gagc 464
<210> 585
<211> 1154
<212> DNA
<213> 单纯疱疹病毒
<400> 585
cgtgtcggca gccgcgctcc gtgtggacga tcggggcgtc ctcgggctca tatagtccca 60
ggggccggcg ggaaggagga gcagcggagg ccgccggccc cccgcccccc aggcgggccc 120
gccccgaacg gaattccatt atgcacgacc ccgccccgac gccggcacgc cgggggcccg 180
tggccgcggc ccgttggtcg aacccccggc cccgcccatc cgcgccatct gccatgggcg 240
gggcgcgagg gcgggtgggc ccgcgccccg ccccgcatgg catctcatta ccgcccgatc 300
cggtggtttc cgcttccgtt ccgcatgcta acgaggaacg ggccgggggc ggggcccggg 360
ccccgacttc ccggttcggc ggtaatgaga tacgagcccc gcgcgcccgt tggccgtccc 420
cgggcccccg gtcccgcccg ccggacgttg ggaccaacgg gacggcgggg cggcccaagg 480
gccgcccgcc ttgccgcccc cccattggcc ggcgggcggg accgccccaa gggggcgggg 540
ccgccgggta aaagaagtga gaacgcgaag cgttcgcact tcgtcccaat atatatatat 600
tattagggcg aagtgcgagc actggcgccg tgcccgactc cgcgccggcc ccgggggcgg 660
gcccgggcgg cggggggcgg gtctctccgg cgcacataaa ggcccggcgc gaccgacgcc 720
cgcagacggc gccggccacg aacgacggga gcggctgcgg agcacgcgga ccgggagcgg 780
gactcgcaga gggccgtcgg agcggacggc gtcggcatcg cgacgccccg gctcgggatc 840
gggatcgcat cggaaaggga cacgcggaaa gacccaccca ccccacccac gaaacacagg 900
ggacgcaccc cgggggcctc cgacgacaga aacccaccgg tccgcctttg tgcacgggta 960
agcaccttgg gtgggcggag gaggggggac gcgggggcgg aggagggggc tcacccgcgt 1020
tcgtgccttc ccgcaggagg aacgtcctcg tcgaggcgac cggcggcgac cgttgcgtgg 1080
accgcttcct gctcgtcggg gcgaccggcg gcgaccgttg cgtggaccgc ttcctgctcg 1140
tcgggcgggg gagc 1154
<210> 586
<211> 266
<212> DNA
<213> 智人
<400> 586
gttctttgaa agcagtcgag ggggcgctag gtgtgggcag ggacgagctg gcgcggcgtc 60
gctgggtgca ccgcgaccac gggcagagcc acgcggcggg aggactacaa ctcccggcac 120
accccgcgcc gccccgcctc tactcccaga aggccgcggg gggtggaccg cctaagaggg 180
cgtgcgctcc cgacatgccc cgcggcgcgc cattaaccgc cagatttgaa tcgcgggacc 240
cgttggcaga ggtggcggcg gcggca 266
<210> 587
<211> 88
<212> PRT
<213> 单纯疱疹病毒
<400> 587
Met Ser Trp Ala Leu Glu Met Ala Asp Thr Phe Leu Asp Asn Met Arg
1 5 10 15
Val Gly Pro Arg Thr Tyr Ala Asp Val Arg Asp Glu Ile Asn Lys Arg
20 25 30
Gly Arg Glu Asp Arg Glu Ala Ala Lys Thr Ala Val His Asp Pro Glu
35 40 45
Arg Pro Leu Leu Arg Ser Pro Gly Leu Leu Pro Lys Ile Ala Pro Asn
50 55 60
Ala Ser Leu Gly Val Ala His Arg Arg Thr Gly Gly Thr Val Thr Asp
65 70 75 80
Ser Pro Arg Asn Pro Val Thr Arg
85
<210> 588
<211> 224
<212> PRT
<213> 单纯疱疹病毒
<400> 588
Met Gly Ile Leu Gly Trp Val Gly Leu Ile Ala Val Gly Val Leu Cys
1 5 10 15
Val Arg Gly Gly Leu Ser Ser Thr Glu Tyr Val Ile Arg Ser Arg Val
20 25 30
Ala Arg Glu Val Gly Asp Ile Leu Lys Val Pro Cys Val Pro Leu Pro
35 40 45
Ser Asp Asp Leu Asp Trp Arg Tyr Glu Thr Pro Ser Ala Ile Asn Tyr
50 55 60
Ala Leu Ile Asp Gly Ile Phe Leu Arg Tyr His Cys Pro Gly Leu Asp
65 70 75 80
Thr Val Leu Trp Asp Arg His Ala Gln Lys Ala Tyr Trp Val Asn Pro
85 90 95
Phe Leu Phe Val Ala Gly Phe Leu Glu Asp Leu Ser His Pro Ala Phe
100 105 110
Pro Ala Asn Thr Gln Glu Thr Glu Thr Arg Leu Ala Leu Tyr Lys Glu
115 120 125
Ile Arg Gln Ala Leu Asp Ser Arg Lys Gln Ala Ala Ser His Thr Pro
130 135 140
Val Lys Ala Gly Cys Val Asn Phe Asp Tyr Ser Arg Thr Arg Arg Cys
145 150 155 160
Val Gly Arg Gln Asp Leu Gly Pro Thr Asn Gly Thr Ser Gly Arg Thr
165 170 175
Pro Val Leu Pro Pro Asp Asp Glu Ala Gly Leu Gln Pro Lys Pro Leu
180 185 190
Thr Thr Pro Pro Pro Ile Ile Ala Thr Leu Asp Pro Thr Pro Arg Arg
195 200 205
Asp Ala Ala Ala Lys Ser Arg Arg Arg Arg Pro His Ser Arg Arg Ile
210 215 220
<210> 589
<211> 3670
<212> DNA
<213> 单纯疱疹病毒
<400> 589
atgtcgggcg tcgggggaga gggagttccc tctgcgcttg cgattctagc ctcgtggggc 60
tggacgttcg acacgccaaa ccacgagtca gggatatcgc cagatacgac tcccgcagat 120
tccattcggg gggccgctgt ggcctcacct gaccaacctt tacacggggg cccggaacgg 180
gaggccacag cgccgtcttt ctccccaacg cgcgcggatg acggcccgcc ctgtaccgac 240
gggccctacg tgacgtttga taccctgttt atggtgtcgt cgatcgacga attagggcgt 300
cgccagctca cggacaccat ccgcaaggac ctgcggttgt cgctggccaa gtttagcatt 360
gcgtgcacca agacctcctc gttttcggga aacgccccgc gccaccacag acgcggggcg 420
ttccagcgcg gcacgcgggc gccgcgcagc aacaaaagcc ttcagatgtt tgtgttgtgc 480
aaacgcaccc acgccgctcg agtgcgagag cagcttcggg tcgttattca gtcccgcaag 540
ccgcgcaagt attacacgcg atcttcggac gggcggctct gccccgccgt ccccgtgttc 600
gtccacgagt tcgtctcgtc cgagccaatg cgcctccacc gagataacgt catgctggcc 660
tcgggggccg agtaaccgcc cccccgcgcc accctcactg cccgtcgcgc gtgtttgatg 720
ttaataaata acgcataaat ttggctggtt gtttgttgtc tttaatggac cgcccgcagg 780
gggggtggca tttcagtgtc gggtgacgag cgcgatccgg ccgggagagg ctccggtgcc 840
cgtcagtggg cagagcgcac atcgcccaca gtccccgaga agttgggggg aggggtcggc 900
aattgaaccg gtgcctagag aaggtggcgc ggggtaaact gggaaagtga tgtcgtgtac 960
tggctccgcc tttttcccga gggtggggga gaaccgtata taagtgcagt agtcgccgtg 1020
aacgttcttt ttcgcaacgg gtttgccgcc agaacacagg taagtgccgt gtgtggttcc 1080
cgcgggcctg gcctctttac gggttatggc ccttgcgtgc cttgaattac ttccacgccc 1140
ctggctgcag tacgtgattc ttgatcccga gcttcgggtt ggaagtgggt gggagagttc 1200
gaggccttgc gcttaaggag ccccttcgcc tcgtgcttga gttgaggcct ggcttgggcg 1260
ctggggccgc cgcgtgcgaa tctggtggca ccttcgcgcc tgtctcgctg ctttcgataa 1320
gtctctagcc atttaaaatt tttgatgacc tgctgcgacg ctttttttct ggcaagatag 1380
tcttgtaaat gcgggccaag atctgcacac tggtatttcg gtttttgggg ccgcgggcgg 1440
cgacggggcc cgtgcgtccc agcgcacatg ttcggcgagg cggggcctgc gagcgcggcc 1500
accgagaatc ggacgggggt agtctcaagc tggccggcct gctctggtgc ctggcctcgc 1560
gccgccgtgt atcgccccgc cctgggcggc aaggctggcc cggtcggcac cagttgcgtg 1620
agcggaaaga tggccgcttc ccggccctgc tgcagggagc tcaaaatgga ggacgcggcg 1680
ctcgggagag cgggcgggtg agtcacccac acaaaggaaa agggcctttc cgtcctcagc 1740
cgtcgcttca tgtgactcca cggagtaccg ggcgccgtcc aggcacctcg attagttctc 1800
gagcttttgg agtacgtcgt ctttaggttg gggggagggg ttttatgcga tggagtttcc 1860
ccacactgag tgggtggaga ctgaagttag gccagcttgg cacttgatgt aattctcctt 1920
ggaatttgcc ctttttgagt ttggatcttg gttcattctc aagcctcaga cagtggttca 1980
aagttttttt cttccatttc aggtgtcgtg agctagcatg tacaggatgc aactcctgtc 2040
ttgcattgca ctaagtcttg cacttgtcac gaattcgata tcgacagccc acccctctcc 2100
tagcccaaga tccgccggcc agttcgccat ggttagatct cccccatgcc catcatgccc 2160
agcacctgag ttcctggggg gaccatcagt cttcctgttc cccccaaaac ccaaggacac 2220
tctcatgatc tcccggaccc ctgaggtcac gtgcgtggtg gtggacgtga gccaggaaga 2280
ccccgaggtc cagttcaact ggtacgtgga tggcgtggag gtgcataatg ccaagacaaa 2340
gccgcgggag gagcagttca acagcacgta ccgtgtggtc agcgtcctca ccgtcctgca 2400
ccaggactgg ctgaacggca aggagtacaa gtgcaaggtc tccaacaaag gcctcccgtc 2460
ctccatcgag aaaaccatct ccaaaaccaa agggcagccc cgagagccac aggtgtacac 2520
cctgccccca tcccaggagg agatgaccaa gaaccaggtc agcctgacct gcctggtcaa 2580
aggcttctac cccagcgaca tcgccgtgga gtgggagagc aatgggcagc cggagaacaa 2640
ctacaagacc acgcctcccg tgctggactc cgacggctcc ttcttcctct acagcaggct 2700
aaccgtggac aagagcaggt ggcaggaggg gaatgtcttc tcatgctccg tgatgcatga 2760
ggctctgcac aaccactaca cacagaagag cctctccctg tctccgggta aatgagtgga 2820
tccaccggat ctagataact gatcataatc agccatacca catttgtaga ggttttactt 2880
gctttaaaaa acctcccaca cctccccctg aacctgaaac ataaaatgaa tgcaattgtt 2940
gttgttaact tgtttattgc agcttataat ggttacaaat aaagcaatag catcacaaat 3000
ttcacaaata aagcattttt ttcactgcat tctagttgtg gtttgtccaa actcatcaat 3060
gtatcttatc ctaggacccc aaaagtttgt ctgcgtattc cagggcgggg ctcagttgaa 3120
tctcccgcag cacctctacc agcaggtccg cggtgggctg gagaaactcg gccgtcccgg 3180
ggcaggcggt cgtcgggggt ggaggcgcgg cgcccacccc gtgtgccgcg cctggcgtct 3240
cctctggggg cgacccgtaa atggttgcag tgatgtaaat ggtgtccgcg gtccagacca 3300
cggtcaaaat gccggccgtg gcgctccggg cgctttcgcc gcgcgaggag ctgacccagg 3360
agtcgaacgg atacgcgtac atatgggcgt cccacccgcg ttcgagcttc tggttgctgt 3420
cccggcctat aaagcggtag gcacaaaatt cggcgcgaca gtcgataatc accaacagcc 3480
caatgggggt gtgttggata acaacgcctc cgcgcggcag gcggtcctgg cgctcccggc 3540
cccgtaccat gatcgcgcgg gtgccgtact caaaaacatg caccacctgc gcggcgtcgg 3600
gcagtgcgct ggtcagcgag gccctggcgt ggcataggct atacgcgatg gtcgtctgtg 3660
gattggacat 3670
<210> 590
<211> 265
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 590
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Ile Ser Thr Ala His Pro Ser Pro Ser Pro Arg Ser
20 25 30
Ala Gly Gln Phe Ala Met Val Arg Ser Pro Pro Cys Pro Ser Cys Pro
35 40 45
Ala Pro Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
50 55 60
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
65 70 75 80
Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr
85 90 95
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
100 105 110
Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
115 120 125
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
130 135 140
Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Gln
145 150 155 160
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met
165 170 175
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
180 185 190
Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn
195 200 205
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
210 215 220
Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val
225 230 235 240
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
245 250 255
Lys Ser Leu Ser Leu Ser Pro Gly Lys
260 265
<210> 591
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 591
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser
20
<210> 592
<211> 14
<212> PRT
<213> 智人
<400> 592
Thr Ala His Pro Ser Pro Ser Pro Arg Ser Ala Gly Gln Phe
1 5 10
<210> 593
<211> 229
<212> PRT
<213> 智人
<400> 593
Ala Met Val Arg Ser Pro Pro Cys Pro Ser Cys Pro Ala Pro Glu Phe
1 5 10 15
Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
20 25 30
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
35 40 45
Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val
50 55 60
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser
65 70 75 80
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
85 90 95
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser
100 105 110
Ser Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro
115 120 125
Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln
130 135 140
Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
145 150 155 160
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
165 170 175
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu
180 185 190
Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser
195 200 205
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
210 215 220
Leu Ser Pro Gly Lys
225
<210> 594
<211> 224
<212> PRT
<213> 单纯疱疹病毒
<400> 594
Met Ser Gly Val Gly Gly Glu Gly Val Pro Ser Ala Leu Ala Ile Leu
1 5 10 15
Ala Ser Trp Gly Trp Thr Phe Asp Thr Pro Asn His Glu Ser Gly Ile
20 25 30
Ser Pro Asp Thr Thr Pro Ala Asp Ser Ile Arg Gly Ala Ala Val Ala
35 40 45
Ser Pro Asp Gln Pro Leu His Gly Gly Pro Glu Arg Glu Ala Thr Ala
50 55 60
Pro Ser Phe Ser Pro Thr Arg Ala Asp Asp Gly Pro Pro Cys Thr Asp
65 70 75 80
Gly Pro Tyr Val Thr Phe Asp Thr Leu Phe Met Val Ser Ser Ile Asp
85 90 95
Glu Leu Gly Arg Arg Gln Leu Thr Asp Thr Ile Arg Lys Asp Leu Arg
100 105 110
Leu Ser Leu Ala Lys Phe Ser Ile Ala Cys Thr Lys Thr Ser Ser Phe
115 120 125
Ser Gly Asn Ala Pro Arg His His Arg Arg Gly Ala Phe Gln Arg Gly
130 135 140
Thr Arg Ala Pro Arg Ser Asn Lys Ser Leu Gln Met Phe Val Leu Cys
145 150 155 160
Lys Arg Thr His Ala Ala Arg Val Arg Glu Gln Leu Arg Val Val Ile
165 170 175
Gln Ser Arg Lys Pro Arg Lys Tyr Tyr Thr Arg Ser Ser Asp Gly Arg
180 185 190
Leu Cys Pro Ala Val Pro Val Phe Val His Glu Phe Val Ser Ser Glu
195 200 205
Pro Met Arg Leu His Arg Asp Asn Val Met Leu Ala Ser Gly Ala Glu
210 215 220
<210> 595
<211> 199
<212> PRT
<213> 单纯疱疹病毒
<400> 595
Met Ser Asn Pro Gln Thr Thr Ile Ala Tyr Ser Leu Cys His Ala Arg
1 5 10 15
Ala Ser Leu Thr Ser Ala Leu Pro Asp Ala Ala Gln Val Val His Val
20 25 30
Phe Glu Tyr Gly Thr Arg Ala Ile Met Val Arg Gly Arg Glu Arg Gln
35 40 45
Asp Arg Leu Pro Arg Gly Gly Val Val Ile Gln His Thr Pro Ile Gly
50 55 60
Leu Leu Val Ile Ile Asp Cys Arg Ala Glu Phe Cys Ala Tyr Arg Phe
65 70 75 80
Ile Gly Arg Asp Ser Asn Gln Lys Leu Glu Arg Gly Trp Asp Ala His
85 90 95
Met Tyr Ala Tyr Pro Phe Asp Ser Trp Val Ser Ser Ser Arg Gly Glu
100 105 110
Ser Ala Arg Ser Ala Thr Ala Gly Ile Leu Thr Val Val Trp Thr Ala
115 120 125
Asp Thr Ile Tyr Ile Thr Ala Thr Ile Tyr Gly Ser Pro Pro Glu Glu
130 135 140
Thr Pro Gly Ala Ala His Gly Val Gly Ala Ala Pro Pro Pro Pro Thr
145 150 155 160
Thr Ala Cys Pro Gly Thr Ala Glu Phe Leu Gln Pro Thr Ala Asp Leu
165 170 175
Leu Val Glu Val Leu Arg Glu Ile Gln Leu Ser Pro Ala Leu Glu Tyr
180 185 190
Ala Asp Lys Leu Leu Gly Ser
195
<210> 596
<211> 3185
<212> DNA
<213> 单纯疱疹病毒
<400> 596
atgctcgccg tccgttccct gcagcacctc tcaaccgtcg tcttgataac ggcgtacggc 60
ctcgtgctcg tgtggtacac cgtcttcggt gccagtccgc tgcaccgatg tatttacgcg 120
gtacgcccca ccggcaccaa caacgacacc gccctcgtgt ggatgaaaat gaaccagacc 180
ctattgtttc tgggggcccc gacgcacccc cccaacgggg gctggcgcaa ccacgcccat 240
atctgctacg ccaatcttat cgcgggtagg gtcgtgccct tccaggtccc acccgacgcc 300
atgaatcgtc ggatcatgaa cgtccacgag gcagttaact gtctggagac cctatggtac 360
acacgggtgc gtctggtggt cgtagggtgg ttcctgtatc tggcgttcgt cgccctccac 420
caacgccgat gtatgtttgg tgtcgtgagt cccgcccaca agatggtggc cccggccacc 480
tacctcttga actacgcagg ccgcatcgta tcgagcgtgt tcctgcagta cccctacacg 540
aaaattaccc gcctgctctg cgagctgtcg gtccagcggc aaaacctggt tcagttgttt 600
gagacggacc cggtcacctt cttgtaccac cgccccgcca tcggggtcat cgtaggctgc 660
gagttgatgc tacgctttgt ggccgtgggt ctcatcgtcg gcaccgcttt catatcccgg 720
ggggcatgtg caatcacata ccccctgttt ctgaccatca ccacctggtg ttttgtctcc 780
accatcggcc tgacagagct gtattgtatt ctgcggcggg gcccggcccc caagaacgca 840
gacaaggccg ccgccccggg gcgatccaag gggctgtcgg gcgtctgcgg gcgctgctgt 900
tccatcatcc tctcgggcat cgcagtgcga ttgtgttata tcgccgtggt ggccggggtg 960
gtgctcgtgg cgcttcacta cgagcaggag atccagaggc gcctgtttga tgtatgacgt 1020
cacatccagg ccggcggaaa ccggaacggc atatgcaaat tggaaactgt cctgtcttgg 1080
ggcccaccca cccgacgcgt catatgcaaa tgaaaatcgg tcccccgagg ccacgtgtag 1140
cctggatccc aacgaccccg cccatgggtc ccaattggcc gtcccgttac caagaccaac 1200
ccagccagca tatccacccc cgcccgggtc cccgcggaag cggaacgggg tatgtgatat 1260
gctaattaaa tacgggaatt tccggggact ttccgggaat ttccggggac tttccgggaa 1320
tttccctaca gaggtgcata ttaacagagc ttttgtcctg gagaatgcca cgtacttatg 1380
gtgtctgatt ggtccttgtc tgtgccggag gtggggcggg ggccccgccc ggggggcgga 1440
acgaggaggg gtttgggaga gccggccccg gcaccacggg tataaggaca tccaccaccc 1500
ggccggtggt ggtgtgcagc cgtgttccaa ccacggtcac gcttcggtgc ctctccccga 1560
ttcgggcccg gtcgctcgct accggtgcgc caccaccaga ggccatatcc gacaccccag 1620
ccccgacggc agccgacagc ccggtcatgg cgactgacat tgatatgcta attgacctcg 1680
gcctggacct ctccgacagc gatctggacg aggacccacc cgagccggcg gagagccgcc 1740
gcgacgacct ggaatcggac agcagcgggg agtgttcctc gtcggacgag gacatggaag 1800
acccccacgg agaggacgga ccggagccga tactcgacgc cgctcgcccg gcggtccgcc 1860
cgtctcgtcc agaagacccc ggcgtaccca gcacccagac gcctcgtccg acggagcggc 1920
agggccccaa cgatcctcaa ccagcgcccc acagtgtgtg gtcgcgcctc ggggcccggc 1980
gaccgtcttg ctcccccgag cagcacgggg gcaaggtggc ccgcctccaa cccccaccga 2040
ccaaagccca gcctgcccgc ggcggacgcc gcgggcgtcg caggggtcgg ggtcgcggtg 2100
gtcccggggc cgccgatggt ttgtcggacc cccgccggcg tgcccccaga accaatcgca 2160
acccgggggg accccgcccc ggggcggggt ggacggacgg ccccggcgcc ccccatggcg 2220
aggcgtggcg cggaagtgag cagcccgacc cacccggagg cccgcggaca cggggcgtgc 2280
gccaagcacc ccccccgcta atgacgctgg cgattgcccc cccgcccgcg gacccccgcg 2340
ccccggcccc ggagcgaaag gcgcccgccg ccgacaccat cgacgccacc acgcggttgg 2400
tcctgcgctc catctccgag cgcgcggcgg tcgaccgcat cagcgagagc tttggccgca 2460
gcgcacaggt catgcacgac ccctttgggg ggcagccgtt tcccgccgcg aatagcccct 2520
gggccccggt gttggcgggc caaggagggc cctttgacgc cgagaccaga cgggtctcct 2580
gggaaacctt ggtcgcccac ggcccgagcc tctatcgcac ttttgccggc aatcctcggg 2640
ccgcatcgac cgccaaggcc atgcgcgact gcgtgctgcg ccaagaaaat ttcatcgagg 2700
cgctggcctc cgccgacgag acgctggcgt ggtgcaagat gtgcatccac cacaacctgc 2760
cgctgcgccc ccaggacccc attatcggga cggccgcggc tgtgctggat aacctcgcca 2820
cgcgcctgcg gccctttctc cagtgctacc tgaaggcgcg aggcctgtgc ggcctggacg 2880
aactgtgttc gcggcggcgt ctggcggaca ttaaggacat tgcatccttc gtgtttgtca 2940
ttctggccag gctcgccaac cgcgtcgagc gtggcgtcgc ggagatcgac tacgcgaccc 3000
ttggtgtcgg ggtcggagag aagatgcatt tctacctccc cggggcctgc atggcgggcc 3060
tgatcgaaat cctagacaca caccgccagg agtgttcgag tcgtgtctgc gagttgacgg 3120
ccagtcacat cgtcgccccc ccgtacgtgc acggcaaata tttttattgc aactccctgt 3180
tttag 3185
<210> 597
<211> 338
<212> PRT
<213> 单纯疱疹病毒
<400> 597
Met Leu Ala Val Arg Ser Leu Gln His Leu Ser Thr Val Val Leu Ile
1 5 10 15
Thr Ala Tyr Gly Leu Val Leu Val Trp Tyr Thr Val Phe Gly Ala Ser
20 25 30
Pro Leu His Arg Cys Ile Tyr Ala Val Arg Pro Thr Gly Thr Asn Asn
35 40 45
Asp Thr Ala Leu Val Trp Met Lys Met Asn Gln Thr Leu Leu Phe Leu
50 55 60
Gly Ala Pro Thr His Pro Pro Asn Gly Gly Trp Arg Asn His Ala His
65 70 75 80
Ile Cys Tyr Ala Asn Leu Ile Ala Gly Arg Val Val Pro Phe Gln Val
85 90 95
Pro Pro Asp Ala Met Asn Arg Arg Ile Met Asn Val His Glu Ala Val
100 105 110
Asn Cys Leu Glu Thr Leu Trp Tyr Thr Arg Val Arg Leu Val Val Val
115 120 125
Gly Trp Phe Leu Tyr Leu Ala Phe Val Ala Leu His Gln Arg Arg Cys
130 135 140
Met Phe Gly Val Val Ser Pro Ala His Lys Met Val Ala Pro Ala Thr
145 150 155 160
Tyr Leu Leu Asn Tyr Ala Gly Arg Ile Val Ser Ser Val Phe Leu Gln
165 170 175
Tyr Pro Tyr Thr Lys Ile Thr Arg Leu Leu Cys Glu Leu Ser Val Gln
180 185 190
Arg Gln Asn Leu Val Gln Leu Phe Glu Thr Asp Pro Val Thr Phe Leu
195 200 205
Tyr His Arg Pro Ala Ile Gly Val Ile Val Gly Cys Glu Leu Met Leu
210 215 220
Arg Phe Val Ala Val Gly Leu Ile Val Gly Thr Ala Phe Ile Ser Arg
225 230 235 240
Gly Ala Cys Ala Ile Thr Tyr Pro Leu Phe Leu Thr Ile Thr Thr Trp
245 250 255
Cys Phe Val Ser Thr Ile Gly Leu Thr Glu Leu Tyr Cys Ile Leu Arg
260 265 270
Arg Gly Pro Ala Pro Lys Asn Ala Asp Lys Ala Ala Ala Pro Gly Arg
275 280 285
Ser Lys Gly Leu Ser Gly Val Cys Gly Arg Cys Cys Ser Ile Ile Leu
290 295 300
Ser Gly Ile Ala Val Arg Leu Cys Tyr Ile Ala Val Val Ala Gly Val
305 310 315 320
Val Leu Val Ala Leu His Tyr Glu Gln Glu Ile Gln Arg Arg Leu Phe
325 330 335
Asp Val
<210> 598
<211> 512
<212> PRT
<213> 单纯疱疹病毒
<400> 598
Met Ala Thr Asp Ile Asp Met Leu Ile Asp Leu Gly Leu Asp Leu Ser
1 5 10 15
Asp Ser Asp Leu Asp Glu Asp Pro Pro Glu Pro Ala Glu Ser Arg Arg
20 25 30
Asp Asp Leu Glu Ser Asp Ser Ser Gly Glu Cys Ser Ser Ser Asp Glu
35 40 45
Asp Met Glu Asp Pro His Gly Glu Asp Gly Pro Glu Pro Ile Leu Asp
50 55 60
Ala Ala Arg Pro Ala Val Arg Pro Ser Arg Pro Glu Asp Pro Gly Val
65 70 75 80
Pro Ser Thr Gln Thr Pro Arg Pro Thr Glu Arg Gln Gly Pro Asn Asp
85 90 95
Pro Gln Pro Ala Pro His Ser Val Trp Ser Arg Leu Gly Ala Arg Arg
100 105 110
Pro Ser Cys Ser Pro Glu Gln His Gly Gly Lys Val Ala Arg Leu Gln
115 120 125
Pro Pro Pro Thr Lys Ala Gln Pro Ala Arg Gly Gly Arg Arg Gly Arg
130 135 140
Arg Arg Gly Arg Gly Arg Gly Gly Pro Gly Ala Ala Asp Gly Leu Ser
145 150 155 160
Asp Pro Arg Arg Arg Ala Pro Arg Thr Asn Arg Asn Pro Gly Gly Pro
165 170 175
Arg Pro Gly Ala Gly Trp Thr Asp Gly Pro Gly Ala Pro His Gly Glu
180 185 190
Ala Trp Arg Gly Ser Glu Gln Pro Asp Pro Pro Gly Gly Pro Arg Thr
195 200 205
Arg Gly Val Arg Gln Ala Pro Pro Pro Leu Met Thr Leu Ala Ile Ala
210 215 220
Pro Pro Pro Ala Asp Pro Arg Ala Pro Ala Pro Glu Arg Lys Ala Pro
225 230 235 240
Ala Ala Asp Thr Ile Asp Ala Thr Thr Arg Leu Val Leu Arg Ser Ile
245 250 255
Ser Glu Arg Ala Ala Val Asp Arg Ile Ser Glu Ser Phe Gly Arg Ser
260 265 270
Ala Gln Val Met His Asp Pro Phe Gly Gly Gln Pro Phe Pro Ala Ala
275 280 285
Asn Ser Pro Trp Ala Pro Val Leu Ala Gly Gln Gly Gly Pro Phe Asp
290 295 300
Ala Glu Thr Arg Arg Val Ser Trp Glu Thr Leu Val Ala His Gly Pro
305 310 315 320
Ser Leu Tyr Arg Thr Phe Ala Gly Asn Pro Arg Ala Ala Ser Thr Ala
325 330 335
Lys Ala Met Arg Asp Cys Val Leu Arg Gln Glu Asn Phe Ile Glu Ala
340 345 350
Leu Ala Ser Ala Asp Glu Thr Leu Ala Trp Cys Lys Met Cys Ile His
355 360 365
His Asn Leu Pro Leu Arg Pro Gln Asp Pro Ile Ile Gly Thr Ala Ala
370 375 380
Ala Val Leu Asp Asn Leu Ala Thr Arg Leu Arg Pro Phe Leu Gln Cys
385 390 395 400
Tyr Leu Lys Ala Arg Gly Leu Cys Gly Leu Asp Glu Leu Cys Ser Arg
405 410 415
Arg Arg Leu Ala Asp Ile Lys Asp Ile Ala Ser Phe Val Phe Val Ile
420 425 430
Leu Ala Arg Leu Ala Asn Arg Val Glu Arg Gly Val Ala Glu Ile Asp
435 440 445
Tyr Ala Thr Leu Gly Val Gly Val Gly Glu Lys Met His Phe Tyr Leu
450 455 460
Pro Gly Ala Cys Met Ala Gly Leu Ile Glu Ile Leu Asp Thr His Arg
465 470 475 480
Gln Glu Cys Ser Ser Arg Val Cys Glu Leu Thr Ala Ser His Ile Val
485 490 495
Ala Pro Pro Tyr Val His Gly Lys Tyr Phe Tyr Cys Asn Ser Leu Phe
500 505 510
<210> 599
<211> 931
<212> DNA
<213> 单纯疱疹病毒
<400> 599
gcagcccggg ccccccgcgg ccgagacgag cgagttagac aggcaagcac tactcgcctc 60
tgcacgcaca tgcttgcctg tcaaactcta ccaccccggc acgctctctg tctccatggc 120
ccgccgccgc cgccatcgcg gcccccgccg cccccggccg cccgggccca cgggcgccgt 180
cccaaccgca cagtcccagg taactaatgg gcggccccgg ccgcccttcc cgcttccggc 240
aattcccgcg gcccttaatg ggcaaccccg gtattccccg cctcccgcgc cgcgcgtaac 300
cactcccctg gggttccggg ttatgctaat tgcttttttg gcggaacaca cggcccctcg 360
cgcattggcc cgcgggtcgc tcaatgaacc cgcattggtc ccctggggtt ccgggtatgg 420
taatgagttt cttcgggaag gcgggaagcc ccggggcacc gacgcaggcc aagcccctgt 480
tgcgtcggtg ggaggggcat gctaatgggg ttctttgggg gacaccgggt tggtccccca 540
aatcgggggc cgggccgtgc atgctaatga tattctttgg gggcgccggg ttggtccccg 600
gggacggggc cgccccgcgg tgggcctgcc tcccctggga cgcgcggcca ttgggggaat 660
cgtcactgcc gcccctttgg ggaggggaaa ggcgtggggt ataagttagc cctggcccga 720
cagtctggtc gcatttgcac ctcggcactc ggagcgagac gcagcagcca ggcagactcg 780
ggccgccccc tctccgcatc accacagaag ccccgcctac gttgcgaccc ccagggaccc 840
tccgtccgcg accctccagc cgcatacgac ccccatggag ccccgccccg gagcgagtac 900
ccgccggcct gagggccgcc cccagcgcga g 931
<210> 600
<211> 29
<212> PRT
<213> 单纯疱疹病毒
<400> 600
Met Ala Arg Arg Arg Arg His Arg Gly Pro Arg Arg Pro Arg Pro Pro
1 5 10 15
Gly Pro Thr Gly Ala Val Pro Thr Ala Gln Ser Gln Val
20 25
Claims (14)
1.一种单纯疱疹病毒HSV载体的制剂，所述制剂由下列组分组成：
单纯疱疹病毒HSV载体所表达的病毒的悬液，
甘油，
水，
其中，所述制剂中甘油的浓度为5％；
其中所述单纯疱疹病毒HSV载体，其包含编码IL12、IL15和IL15受体α亚单位的表达盒，其中，所述表达盒的侧翼具有经修饰的ICP47启动子；
其中，所述IL15受体α亚单位为变体1(SEQ ID NO.3)；
其中，所述单纯疱疹病毒HSV载体还进一步包含编码一种或多种PD-L1阻断肽的表达盒，和编码IgG4 Fc区的序列，其中一经表达，IgG4 Fc区和所述PD-L1阻断肽的3’-端连接；
其中，所述单纯疱疹病毒HSV载体还进一步包含经修饰的ICP34.5区。
2.权利要求1所述的单纯疱疹病毒HSV载体的制剂，其中，所述经修饰的ICP47启动子的序列包含SEQ ID No.584。
3.权利要求1所述的单纯疱疹病毒HSV载体的制剂，其中，IL12、IL15和IL15受体α亚单位的编码序列之间的框内具有编码自剪切肽2A的核酸序列。
4.权利要求3所述的单纯疱疹病毒HSV载体的制剂，其中，所述自剪切肽2A的氨基酸序列为：ATNF-SLLKQAGDVEENPGP。
5.权利要求1所述的单纯疱疹病毒HSV载体的制剂，其中，一个或多个IRES序列位于IL12、IL15和IL15受体α亚单位的编码序列之间。
6.权利要求1所述的单纯疱疹病毒HSV载体的制剂，其中，所述IL15和IL15受体α亚单位通过双向启动子表达。
7.权利要求1所述的单纯疱疹病毒HSV载体的制剂，其中，所述IL15和IL15受体α亚单位各自跟随一个编码Lys5或Glu5的核酸序列。
8.权利要求1所述的单纯疱疹病毒HSV载体的制剂，其中，所述包含IL12、IL15和IL15受体α亚单位的表达盒被插入到HSV的内部重复区或HSV基因组的末端重复区中。
9.权利要求1所述的单纯疱疹病毒HSV载体的制剂，其中，所述PD-L1阻断肽的表达盒被插入HSV病毒基因的UL3和UL4之间。
10.权利要求1-9任一项所述的单纯疱疹病毒HSV载体的制剂，其中，在所述单纯疱疹病毒HSV载体的ICP4或ICP27调控区中进一步包含NFkB和OCT4/SOX2增强元件。
11.权利要求1-9任一项所述的单纯疱疹病毒HSV载体的制剂，其中，所述单纯疱疹病毒HSV载体的ICP34.5基因部分缺失或无功能。
12.权利要求1至11任一项所述的单纯疱疹病毒HSV载体的制剂，在制备治疗癌症的药物中的应用。
13.根据权利要求12所述的应用，其中，所述癌症选自：肠癌、肺癌、乳腺癌、膀胱癌、结肠癌、直肠癌、小细胞肺癌、非小细胞肺癌、子宫颈癌前列腺癌、B细胞淋巴瘤、黑色素瘤、和成胶质细胞瘤。
14.根据权利要求12或13所述的应用，其中所述的治疗癌症通过皮下注射、瘤内注射或静脉注射的方式来给药。
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| CN109563490A (zh) * | 2016-06-09 | 2019-04-02 | 大学之母博洛尼亚大学 | 具有经修饰的糖蛋白b的疱疹病毒 |
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