CN106574271B - 嵌合西尼罗/登革病毒和使用方法 - Google Patents
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Abstract
本文公开了嵌合黄病毒，其包括来自西尼罗病毒(WNV)的非编码区、非结构蛋白以及C蛋白的至少一部分，和来自登革病毒(DENV)的prM蛋白和E蛋白。所述DENV可以是DEN1血清型、DEN2血清型、DEN3血清型或DEN4血清型。本文还公开了用于引起受试者中的免疫应答(如针对一种或多种DENV血清型的免疫应答)的组合物和方法。在具体的实施方案中，所述组合物包括一种或多种包括WN/DENV嵌合核酸的灭活病毒(如包括WN/DEN1嵌合体、WN/DEN2嵌合体、WN/DEN3嵌合体以及WN/DEN4嵌合体的四价灭活疫苗)。可将所述组合物给药至受试者以引起免疫应答。
Description
相关申请的交叉引用
本申请要求于2014年6月20日提交的美国临时申请No.62/015,265的优先权，所述临时申请以引用的方式全文纳入本文。
技术领域
本公开内容涉及嵌合黄病毒，特别是嵌合西尼罗病毒/登革病毒构建体。此外，其涉及在引起受试者中的免疫应答的方法中使用这些嵌合体的方法。
背景技术
登革病毒(DENV)是全世界发病率和死亡率的最重要的虫媒病毒原因。目前有25亿的人生活在登革地方病地区，其中每年有大约1亿的登革热病例和数十万的登革出血热和登革休克综合症病例(Gubler,Clin.Microbiol. Rev.11:480-496,1998)。尽管目前有若干疫苗处于开发或临床试验中，但目前没有针对四种DENV血清型(DENV 1-4)中的任一种的疫苗是市售可得的。DENV疫苗生产受以下事实妨碍：针对一种血清型的中和抗体不能有效地中和其余DENV血清型(Halstead和O'Rourke,J.Exp.Med.146:201-217, 1977)。事实上，因称为抗体介导的增强的现象所致，在二次感染期间低水平的这些抗体实际上可能增加更严重疾病的风险，这会在针对一种DENV 血清型的抗体以非中和方式结合到另一种血清型的DENV颗粒时发生。这种结合允许带有Fc受体的细胞(如巨噬细胞)的感染增加，其可以改变病毒的感染特征或使得产生登革出血热或登革休克综合症的趋化因子释放 (Halstead和O'Rourke,J.Exp.Med.146:201-217,1977)。
发明内容
本文公开了嵌合黄病毒，其包括来自WNV的非编码区、非结构蛋白和 C蛋白的至少一部分，以及来自DENV的prM蛋白和E蛋白。所述DENV 可以是DEN1血清型、DEN2血清型、DEN3血清型或DEN4血清型。在一些实例中，所述prM和E蛋白来自不同的DENV(例如来自不同的DENV 血清型)。
在一些实施方案中，所述嵌合体包括第一核酸分子，其包括来自西尼罗病毒的5'非编码区、编码C蛋白和非结构蛋白的核酸以及3'非编码区；和第二核酸分子，其与所述第一核酸分子可操作地连接，编码来自DENV 的prM蛋白和E蛋白的至少一部分。
在其他实施方案中，所述嵌合体包括第一核酸分子，其包括来自西尼罗病毒的5'非编码区、编码一部分C蛋白和非结构蛋白的核酸以及3'非编码区；和第二核酸分子，其与所述第一核酸分子可操作地连接，编码来自 DENV的C蛋白、prM蛋白和E蛋白的至少一部分。在一些实例中，编码 prM信号序列的WNV C蛋白部分用来自DENV的信号序列替换。在其他实例中，prM信号序列包括WNV信号序列的5'部分和DENV信号序列的 3'部分。
在一些实例中，嵌合黄病毒包括至少一个核酸或氨基酸置换，其改进了嵌合体特征(如增加在细胞培养物中的复制，降低在蚊子中的感染力或传播性或降低抗体交叉反应性)。在具体的实例中，氨基酸置换是在WNV 或DEN C蛋白、DENV prM蛋白、DENV E蛋白或WNVNS蛋白中。
本文还公开了用于引起受试者中的免疫应答的组合物和方法，所述免疫应答如针对一种或多种DENV血清型的免疫应答。在具体的实施方案中，所述组合物包括一种或多种包括WN/DENV嵌合核酸的灭活病毒(如包括 WN/DEN1嵌合体、WN/DEN2嵌合体、WN/DEN3嵌合体以及WN/DEN4 嵌合体的四价灭活疫苗)。将所述组合物给予受试者以引起免疫应答，如保护性免疫应答。本文还公开了灭活WN/DEN嵌合体的方法。
根据以下参照附图进行的详细描述，本公开内容的上述和其他特征会变得更加清楚。
附图说明
图1A-1D是示出了本文中所描述的野生型或嵌合病毒的基因组结构(organization)的一系列示意图。基因组结构未按比例示出。图1A示出了野生型WNV，其包括5'非编码区(NCR)、包括prM蛋白的信号序列(C(ss)) 的衣壳(C)蛋白、前膜(prM)蛋白、包膜(E)蛋白、非结构(NS)蛋白1-5以及3'NCR。图1B示出了具有I型接合的嵌合WN/DENV，其包括来自WNV的5'NCR、C蛋白、NS蛋白1-5以及3'NCR(空白框)，和来自 DENV的C(ss)、prM蛋白以及E蛋白(阴影框)。图1C示出了具有II型接合的嵌合WN/DENV，其包括来自WNV的5'NCR、C蛋白、NS蛋白1-5 以及3'NCR(空白框)，和来自DENV的prM蛋白和E蛋白(阴影框)。这种病毒包括来自WNV的C(ss)的5'部分和来自DENV的C(ss)的3'部分。图 1D示出了具有III型接合的嵌合WN/DENV，其包括来自WNV的5'NCR、 C蛋白和C(ss)、NS蛋白1-5以及3'NCR(空白框)，和来自DENV的prM 蛋白和E蛋白(阴影框)。
图2A和2B是示出了WN/DENV嵌合体和相应的DEN病毒在感染后 (p.i.)第2天在Vero细胞中(图2A)或在p.i.第4天(左条形柱)和第6 天(右条形柱)在C6/36细胞中(图2B)的生长的图表。
图3A-3D是示出了AG129小鼠的存活曲线的一系列曲线图，所述 AG129小鼠用四价DENV候选疫苗接种并且用WN/DENV-1嵌合体(图 3A)、WN/DENV-2E203嵌合体(图3B)、WN/DENV-3CE345嵌合体(图 3C)或WN/DENV-4C107嵌合体(图3D)攻击。
图4示出了由WNV、WN/DENV嵌合体以及DENV1-4产生的可见空斑的时机(左)，和在6孔板中在p.i.第3天在Vero细胞上的空斑的数字图像(右)。
图5A和5B是示出了96孔Vero细胞板中来自p.i.48小时DENV1-4 (图5A)和p.i.24小时WN/DENV嵌合体(图5B)的免疫染色微病灶的一系列图像。在iSpot光谱读取器(iSpotReader Spectrum)(Autoimmun Diagnostika,GMBH))上使用针对每一种血清型优化的自动计数参数来定量病灶。
序列表
列于本文或所附序列表中的任何核酸和氨基酸序列是使用如37C.F.R. §1.822中所定义的核苷酸碱基和氨基酸的标准字母缩写来显示。在至少一些情况下，仅显示每条核酸序列的一条链，但应理解任何提及所示链时均包括其互补链。
SEQ ID NO:1和2分别是WNV克隆株IC-P991核酸和氨基酸序列。
SEQ ID NO:3和4分别是DEN1 16007核酸和氨基酸序列。
SEQ ID NO:5和6分别是DEN2 16681核酸和氨基酸序列。
SEQ ID NO:7和8分别是DEN3 16562核酸和氨基酸序列。
SEQ ID NO:9和10分别是DEN4 1036核酸和氨基酸序列。
SEQ ID NO:11和12分别是WN/DEN1I型接合嵌合体核酸和氨基酸序列。
SEQ ID NO:13和14分别是WN/DEN2E203-Asp I型嵌合体核酸和氨基酸序列。
SEQ ID NO:15和16分别是WN/DEN3E345-Leu II型接合(BE3345) 嵌合体核酸和氨基酸序列。
SEQ ID NO:17和18分别是WN/DEN3E345-Leu III型接合(CE345) 嵌合体核酸和氨基酸序列。
SEQ ID NO:19和20分别是WN/DEN4C107-Pro I型接合嵌合体核酸和氨基酸序列。
SEQ ID NO:21-23分别是WN/DEN1、WN/DEN2以及WN/DEN4嵌合体的示例性II型接合的氨基酸序列。
具体实施方式
尽管DENV和WNV均是黄病毒，但在细胞培养物中DENV比WNV 复制地更缓慢并且效价更低。这使得DEN病毒或病毒抗原(例如用于开发 DENV疫苗)的产生比WNV更困难。本文中所描述的嵌合WN/DEN病毒在病毒颗粒表面上含有DENV抗原结构，同时保留某些WNV特征(如达到高效价的复制)。所公开的嵌合体因此可以用于开发免疫原性组合物，如灭活的病毒疫苗，用于引起针对DEN病毒的免疫应答。由于在细胞培养物中其比wt DENV生长地快速且更稳固，可比野生型DENV更有效地大量产生这些嵌合体以用于制备灭活病毒。
另外，在DENV接种方案中，重要的是获得针对所有四种DENV血清型的经平衡的免疫力，以使与DENV感染的抗体增强相关的严重疾病结果的潜在风险最小化。因此，对于已获得先前DENV感染但不具有针对所有四种DENV的免疫力的人们来说，灭活的WN/DENV嵌合体和含有其的免疫原性组合物可能是更好的选择。已证明由于复制期间病毒间的干扰，使用四价减毒活重组DENV疫苗(参见美国专利No.7,094,411)在单剂量或多剂量后难以获得经平衡的免疫力。由于将无病毒干扰(不需要复制)，灭活疫苗(单独或作为加强剂)可以潜在地解决该问题。
本文中所公开的嵌合WN/DEN病毒还可以在小鼠中具有毒性和/或产生高病毒血症，因此其可用作攻击剂量以评估DENV候选疫苗的功效。其也可以用作DEN样替代病毒以用于测试DENV候选疫苗功效以及用于更快和/或更有效的DENV诊断。
I.缩写
C 衣壳蛋白
C(ss) C蛋白的prM信号序列部分
DEN或DENV 登革病毒
E 包膜糖蛋白
ELISA 酶联免疫吸附测定
mAb 单克隆抗体
mFRNT 微病灶减少中和测试
NCR 非编码区
pfu 空斑形成单位
p.i. 感染后
prM 前膜蛋白
PRNT 空斑减少中和测试
LD50 50％致死剂量
WN或WNV 西尼罗病毒
WN/DEN 西尼罗/登革病毒嵌合体
II.术语
除非另有说明，根据常规用法使用技术术语。分子生物学中的常用术语的定义可以见于Lewin’s Genes X,ed.Krebs et al,Jones and Bartlett Publishers,2009(ISBN0763766321)；Kendrew et al.(eds.),The Encyclopedia of Molecular Biology,published by Blackwell Publishers,1994(ISBN 0632021829)；Robert A.Meyers(ed.),Molecular Biology and Biotechnology:a Comprehensive Desk Reference,publishedby Wiley,John&Sons,Inc.,1995 (ISBN 0471186341)；和George P.Rédei,EncyclopedicDictionary of Genetics, Genomics,Proteomics and Informatics,第3版,Springer,2008(ISBN: 1402067534)。
除非另有说明，本文中所使用的所有技术术语和科学术语具有与本公开内容所属领域的普通技术人员通常所理解相同的含义。除非上下文中另有明确说明，单数术语“一”、“一个”和“所述”包括复数指代对象。类似地，除非上下文中另有明确说明，词语“或”意欲包括“和”。还应理解，对于核酸或多肽给出的所有碱基大小(长度)或氨基酸大小(长度)和所有分子量或分子质量值是近似的，并且为了描述而提供。出于所有目的，本文中所提及的所有出版物、专利申请、专利以及其他参考文献以引用的方式全文纳入。本文中所提及的所有GenBank登录号以引用的方式全文纳入。虽然可以在本公开内容的实施或测试中使用与本文中所描述的那些类似或等同的方法和材料，但在下文描述了合适的方法和材料。如出现冲突，以本说明书(包括对术语的解释)为准。另外，材料、方法以及实施例仅仅是实例性的，不意欲进行限制。
为了便于阅读本发明的各个实施方案，提供了以下对具体术语的解释：
抗体：包括一种或多种基本上由免疫球蛋白基因或免疫球蛋白基因片段编码的多肽的蛋白(或蛋白复合物)。所识别的免疫球蛋白基因包括κ、λ、α、γ、δ、ε和μ恒定区基因以及无数免疫球蛋白可变区基因。将轻链分类为κ或λ。将重链分类为γ、μ、α、δ或ε，其依次分别将免疫球蛋白类别定义为IgG、IgM、IgA、IgD以及IgE。
基本免疫球蛋白(抗体)结构单元一般是四聚体。每一四聚体由两对相同的多肽链构成，每一对具有一条“轻”链(约25kDa)和一条“重”链(约50-70kDa)。每一条链的N-末端限定约100到110个或更多个主要负责抗原识别的氨基酸的可变区。术语“可变轻链”(VL)和“可变重链” (VH)分别是指这些轻链和重链。
本文使用的术语“抗体”包括完整免疫球蛋白以及许多充分表征的片段。例如，结合到靶蛋白(或蛋白或融合蛋白内的表位)的Fab、Fv以及单链Fv(scFv)还将是所述蛋白(或表位)的特异性结合剂。这些抗体片段定义如下：(1)Fab，含有抗体分子的单价抗原结合片段的片段，其通过用酶木瓜蛋白酶消化整个抗体以产生完整轻链和一条重链的一部分而产生；(2)Fab'，通过用胃蛋白酶处理整个抗体、随后还原以产生完整轻链和重链的一部分而获得的抗体分子的片段；每个抗体分子获得两个Fab'片段； (3)(Fab')2，通过用胃蛋白酶处理整个抗体而随后不进行还原获得的抗体的片段；(4)F(ab')2，通过两个二硫键连接的两个Fab'片段的二聚体；(5)Fv，遗传工程片段，其含有轻链的可变区和重链的可变区，表达为两条链；以及(6)单链抗体，遗传工程分子，其含有轻链的可变区、重链的可变区，通过合适的多肽接头连接为遗传融合的单链分子。制备这些片段的方法是常规的(参见，例如，Harlow和Lane,Using Antibodies:A Laboratory Manual, CSHL,New York,1999)。
用于本公开内容的方法和装置的抗体可以是单克隆或多克隆抗体。仅举例来说，单克隆抗体可以根据Kohler和Milstein的经典方法(Nature 256:495-97,1975)或其衍生方法从鼠杂合瘤中制备。用于单克隆抗体生产的详细步骤记载于Harlow和Lane,UsingAntibodies:A Laboratory Manual, CSHL,New York,1999中。
抗体结合亲和力：单一抗体结合位点与配体(例如，抗原或表位)之间的结合强度。抗体结合位点X对配体Y的亲和力由解离常数(Kd)表示，其是占据存在于溶液中的X的结合位点的一半所需的Y的浓度。更小的 Kd指示X与Y之间的更强或更高的亲和相互作用，并且需要更低的配体浓度来占据所述位点。一般来说，可以通过改变、修饰和/或置换通过抗体互补位识别的表位中的一个或多个氨基酸来影响抗体结合亲和力。在一个实例中，抗体结合亲和力通过终点滴定在Ag-ELISA测定中测量。
抗原：可在动物中刺激抗体产生或T细胞应答的化合物、组合物或物质，包括注射或吸收到动物中的组合物。抗原与特定体液免疫或细胞免疫的产物(包括由异源性免疫原诱导的那些)反应。在一个实施方案中，抗原是病毒抗原，如黄病毒E蛋白。
衣壳蛋白(C蛋白)：起作用以在病毒组装期间将病毒RNA包装于核衣壳核心中的黄病毒结构蛋白。C蛋白的C-末端部分包括内部信号序列(在本文中的一些实例中被称为C(ss))以用于将prM蛋白转运到内质网中，其中发生C和prM蛋白的裂解。这种信号序列在不同黄病毒中长度不同。例如，DEN病毒的C(ss)是14个氨基酸，而WNV的C(ss)是18个氨基酸。
嵌合体：由具有不同来源的的部分(如至少两种核酸或多肽)构成的分子(例如，核酸或蛋白)，所述部分尽管在其天然状态下通常是未连接的，但经连接(join)或连接(link)以形成单一连续分子。嵌合体可以包括端对端连接(例如一个序列的氨基端连接到另一序列的羧基端)的核酸或多肽，或可以包括来自一个分子的包埋在另一个分子的序列内的序列(例如嵌合体的氨基端和羧基端来自一个分子，而插入序列来自另一个分子)。
嵌合体可以包括嵌合蛋白，例如由来自多于一种蛋白的氨基酸构成的蛋白。嵌合体还可以包括由来自多于一种来源的核酸序列构成的嵌合核酸，如编码嵌合蛋白的嵌合核酸。在其他实例中，嵌合体可以包括嵌合基因组，如黄病毒基因组，其由来自两种或更多种黄病毒的序列构成。例如，嵌合黄病毒基因组可以包含来自多于一种黄病毒基因组(如西尼罗病毒和登革病毒)的核酸序列。在一些实例中，嵌合黄病毒包括编码一种或多种来自第一黄病毒的蛋白的核酸，和编码一种或多种来自第二黄病毒的蛋白的核酸。在具体的实例中，嵌合黄病毒由编码来自西尼罗病毒基因组的非结构蛋白和C蛋白或其一部分的核酸构成，所述核酸连接到编码来自登革病毒基因组(如DEN1、DEN2、DEN3或DEN4)的prM蛋白和E蛋白的至少一部分(和任选地C蛋白的一部分)的核酸。示例性的嵌合黄病毒示意性地示于图1A-1D中。
保守性置换：用具有相似生物化学特性的不同氨基酸残基置换蛋白质序列中的一个氨基酸残基。通常，保守性置换对所得多肽活性的影响极小或没有影响。例如，理想地，包括一个或多个保守性置换(例如1-10、2-5 或10-20或不多于2、5、10、20、30、40或50个置换)的黄病毒蛋白(如 prM、E或非结构蛋白)保留野生型蛋白的结构和功能。多肽可以通过使用例如标准方法(如定点诱变或PCR)操纵编码所述多肽的核苷酸序列产生以含有一个或多个保守性置换。在一个实例中，通过用含有变体蛋白的病毒感染细胞并确定其复制能力，通过产生含有变体蛋白的病毒并且确定其神经毒力或神经侵袭特性，和/或通过测试抗体交叉反应性，可容易地选择这类变体以用于其他测试。
包膜糖蛋白(E蛋白)：介导黄病毒病毒粒子与宿主细胞上细胞受体结合的黄病毒结构蛋白。黄病毒E蛋白为膜融合所需，并且是诱导针对黄病毒感染的保护性免疫的主要抗原。黄病毒E蛋白影响宿主范围、组织嗜性以及病毒毒力。黄病毒E蛋白含有三个结构和功能域，DI-DIII。在成熟病毒颗粒中，E蛋白形成平躺并且在病毒表面上形成致密晶格的头到尾的同质二聚体。
黄病毒交叉反应性抗体：识别(即，特异性结合到)存在于来自多于一种黄病毒种类的肽上的表位的抗体。黄病毒交叉反应性抗体被分类为复合物交叉反应性或群组交叉反应性抗体。复合物交叉反应性抗体识别由复合物(如JE病毒复合物或DENV复合物)内的所有病毒共有的表位。群组交叉反应性抗体识别由黄病毒属(Flavivirus)的所有成员共有的表位。
抗体交叉反应性进一步细分在亚复合物和亚群组交叉反应性类别内。亚复合物交叉反应性抗体识别由特定黄病毒复合物的大多数而非所有的成员(例如，DEN-1、DEN-2以及DEN-3，而非DEN-4)共有的表位，而亚群组交叉反应性抗体识别由来自若干复合物的黄病毒而非黄病毒群组的所有成员(例如，DENV和JE病毒复合物的所有成员，而非蝉传病毒复合物的所有成员)共有的表位。
黄病毒非-结构蛋白：存在黄病毒的七种非-结构(NS)蛋白，NS1、 NS2A、NS2B、NS3、NS4A、NS4B、以及NS5，其由为3'的黄病毒基因组部分编码成结构蛋白。NS1与RNA复制有关并且已被证明从经感染的哺乳动物细胞中分泌(Post et al.,Virus Res.18:291-302,1991；Mackenzie et al., Virology 220:232-240,1996；Muylaert et al.,Virology 222:159-168,1996)。NS1 可以引起强的体液免疫应答并且是潜在的疫苗候选物(Shlesinger etal.,J. Virol.60:1153-1155,1986；Qu et al.,J.Gen.Virol.74:89-97,1993)。NS2被裂解成NS2A和NS2B。NS2A参与RNA复制和病毒颗粒组装和分泌，并且 NS2B与NS3形成复合物并且充当裂解病毒多聚蛋白部分的NS3蛋白酶的辅因子。NS3还充当RNA解旋酶并且在复制期间用于将病毒RNA展开(Li et al.,J.Virol.73:3108-3116,1999)。虽然NS4A和NS4B的确切功能仍有待阐明，但认为它们参与RNA复制和RNA运输(Lindenbach和Rice,in FieldsVirology,Knipe和Howley,eds.,Lippincott,Williams和Wilkins,991-1041, 2001中)。最后，NS5蛋白是参与基因组复制的RNA依赖性RNA聚合酶 (Rice et al.,Science 229:726-733,1985)。NS5还显示通常见于RNA帽化酶中的甲基转移酶活性(Koonin,J.Gen.Virol.74:733-740,1993)。
黄病毒结构蛋白：黄病毒的衣壳(C)、前膜(prM)以及包膜(E)蛋白是病毒的结构蛋白。黄病毒基因组由长度大约是11kb的正义RNA组成。所述基因组具有5'帽子，但缺少3'聚腺苷酸化尾巴(Wengler et al.,Virology 89:423-437,1978)并且被翻译成一种多聚蛋白。结构蛋白(C、PrM以及E) 位于多聚蛋白的氨基末端，之后是非结构蛋白(NS1-5)。多聚蛋白通过病毒和宿主衍生的蛋白酶裂解成单个蛋白。C蛋白形成病毒衣壳，而prM和E 蛋白包埋在周围包膜中(Russell et al.,The Togaviruses:Biology,Structure, andReplication,Schlesinger ed.,Academic Press,1980)。E蛋白在结合到宿主细胞受体方面起作用，引起受体介导的内吞作用。在低pH的内体中，E蛋白经历构象变化，引起病毒包膜与内体膜之间的融合。认为prM蛋白可稳定E蛋白直至病毒离开经感染的细胞，此时prM被裂解成成熟M蛋白(综述于Lindenbach和Rice,In:Fields Virology,Knipe和Howley,eds.,Lippincott,Williams和Wilkins,991-1041,2001中)。
异源的：源自不同基因来源或物种。例如，包括来自两种(或更多种) 不同基因来源或来自序列(来自单一基因来源)的两个(或更多个)原本分离的片段的核酸的嵌合核酸被视为异源核酸。类似地，包括来自两种(或更多种)来自单一基因来源的不同蛋白或两种(或更多种)来自不同基因来源的蛋白(如融合蛋白)的肽的多肽被视为异源多肽。例如，与包含DENV 基因组部分的核酸可操作地连接的包含WNV基因组部分的核酸是异源核酸。类似地，包括连接到DENV多肽或其部分的WNV多肽或其部分的多肽是异源多肽。
在使用术语异源的另一个实例中，与细胞异源的核酸来源于非表达其的细胞的生物体或物种。在一个具体的非限制性实例中，异源核酸包括在细菌细胞(如大肠杆菌(E.coli)细胞)中或在藻类、植物、昆虫(例如 C6/36)或哺乳动物(例如，Vero)细胞中存在或表达的黄病毒核酸。用于将异源核酸引入细菌、藻类、植物、昆虫以及哺乳动物细胞中的方法是本领域公知的，包括用病毒核酸感染细胞，或用核酸转化，例如电穿孔、脂质体转染以及粒子枪加速。
免疫应答：免疫系统的细胞(如B细胞、T细胞、巨噬细胞或多形核细胞)对刺激物(如抗原)的应答。免疫反应可以包括参与宿主防御反应的机体的任何细胞，例如分泌干扰素或细胞因子的上皮细胞。免疫应答包括但不限于先天性免疫应答或炎症。
灭活病毒：已显现不能在宿主细胞中复制(并且因此不具有毒性)但可以引起免疫应答的病毒(如病毒疫苗)。灭活病毒(如包括本文中所描述的核酸嵌合体的病毒)的方法包括化学处理(例如甲醛)、物理处理(如热)、照射或其组合。
分离的：“分离的”或“纯化的”生物组分(如核酸、肽、蛋白质、蛋白复合物或颗粒)已经基本上从制品中的其他组分或其中存在所述组分的生物体细胞中的其他生物组分(即，其他染色体的和染色体外的DNA和 RNA以及蛋白)中分离、产生或纯化。因此，已经被“分离的”或“纯化的”核酸、肽以及蛋白包括通过标准纯化方法纯化的核酸和蛋白质。该术语还包括核酸，通过在宿主细胞中重组表达制备的肽和蛋白，以及化学合成的核酸或蛋白。术语“分离的”或“纯化的”不需要绝对纯度；而是意欲作为相对的术语。因此，例如，分离的生物组分是其中所述生物组分比处于细胞内天然环境下或其他产生容器中的生物组分更富集的生物组分。优选地，纯化制品以使生物组分相当于所述制品的总生物组分含量的至少 50％，如至少70％、至少90％、至少95％或更大。
核酸分子：核苷酸的多聚形式，其可以包括RNA、cDNA、基因组DNA 以及上文的合成形式和混合多聚物的正义和反义链。核苷酸是指核糖核苷酸、脱氧核苷酸或任一类型的核苷酸的修饰形式。本文中使用的术语“核酸分子”与“核酸”和“多聚核苷酸”同义。除非另有说明，核酸分子的长度通常为至少10个碱基。该术语包括单链和双链形式的DNA。多聚核苷酸可包括通过天然存在的和/或非天然存在的核苷酸连接键(linkage)而连接在一起的天然存在的和经修饰的核苷酸中的任一种或两种。
可操作地连接：当第一核酸与第二核酸置于功能性关系中时，所述第一核酸与第二核酸可操作地连接。一般来说，可操作地连接的DNA序列是连续的，并且在必要时在同一阅读框中连接两个蛋白编码区。可操作地连接的核酸包括与第二核酸的5'或3'端相邻的第一核酸。在其他实例中，当第二核酸包埋在第一核酸内时，其与第一核酸可操作地连接，例如，其中核酸构建体包括(依次)第一核酸的一部分、第二核酸以及第一核酸的剩余部分。包埋在第一核酸内的第二核酸的实例示意性地示于图1B-1D中。
可药用的载体：可用于本公开内容的可药用的载体(载体)是常规的。 Remington:The Science and Practice of Pharmacy)》,The University of the Sciences inPhiladelphia,Editor,Lippincott,Williams,&Wilkins,Philadelphia, PA,第21版(2005)记载了适用于一种或多种治疗组合物(如一种或多种多瘤病毒衣壳多肽或其片段)和其他药物试剂的药物递送的组合物和制剂。
一般来说，载体的性质将取决于所采用的给药的具体方式。例如，肠胃外制剂通常包含包括可药用的和生理学上可接受的液体(例如水、生理盐水、平衡盐溶液、水性葡萄糖、甘油等)作为载体的可注射液体。对于固体组合物(例如，粉末、丸剂、片剂或胶囊形式)，常规的非毒性固体载体可包括，例如药物级的甘露糖醇、乳糖、淀粉或硬脂酸镁。除生物学上中性的载体以外，待给药的药物组合物可以含有少量的非毒性辅助物质，如湿润剂或乳化剂、防腐剂以及pH缓冲剂等，例如乙酸钠或山梨糖醇单月桂酸酯。
前膜蛋白(prM蛋白)：黄病毒结构蛋白。prM蛋白是大约25kDa的蛋白，其为膜(M)蛋白的胞内前体。认为prM在不成熟的病毒粒子转运到细胞表面期间稳定E蛋白。当病毒离开经感染的细胞时，prM蛋白被裂解成成熟M蛋白，其是病毒包膜的一部分(综述于Lindenbach和Rice,In: Fields Virology,Knipe和Howley,eds.,Lippincott,Williams和Wilkins,991-1041,2001中)。
纯化的：术语纯化的不需要绝对纯度；而是意欲作为相对的术语。因此，例如，纯化的核酸制品是其中核酸比处于其天然环境(如在细胞内) 或于制品或产生容器中的核酸更富集的核酸。在其他实例中，纯化的病毒制品是其中病毒比在细胞或生物体、制品或产生容器中更富集的病毒。纯化的核酸或病毒还包括基本上不含不需要的组分(如灭活剂)的核酸或病毒。优选地，纯化制品以使核酸或病毒代表制品的总含量的至少50％。在一些实施方案中，纯化的制品含有至少60％、至少70％、至少80％、至少 85％、至少90％、至少95％、至少98％、至少99％或更多的核酸或病毒。
重组的核酸：不是天然存在的或具有通过人工组合两个原本分离的序列片段而制得的序列的核酸分子。这种人工组合可通过化学合成或更通常地通过人工操作分离的核酸片段来实现，例如通过遗传工程技术，如 Sambrook et al.(ed.),Molecular Cloning:ALaboratory Manual,第2版,第 1-3卷,Cold Spring Harbor Laboratory Press,ColdSpring Harbor,NY,1989中所描述的那些。术语重组包括已仅通过添加、置换或删除天然核酸分子的一部分来改变的核酸。示例性的重组核酸示意性地示于图1B-1D中。
序列同一性：两个核酸序列或两个氨基酸序列之间的相似性是以序列之间的相似性表示，或者称为序列同一性。序列同一性通常以同一性(或相似性或同源性)百分比来度量；百分比越高，两个序列越相似。
比对用于比较的序列的方法是本领域中公知的。多种程序和比对算法记载于：Smith和Waterman(Adv.Appl.Math.,2:482,1981)；Needleman和 Wunsch(J.Mol.Biol.,48:443,1970)；Pearson和Lipman(Proc.Natl.Acad. Sci.,85:2444,1988)；Higgins和Sharp(Gene,73:237-44,1988)；Higgins和 Sharp(CABIOS,5:151-53,1989)；Corpet et al.(Nuc.Acids Res.,16:10881-90, 1988)；Huang et al.(Comp.Appls.Biosci.,8:155-65,1992)；和Pearson et al. (Meth.Mol.Biol.,24:307-31,1994).Altschul et al.(NatureGenet.,6:119-29, 1994)提出了对序列比对方法和同源性计算的详细见解。
比对工具ALIGN(Myers和Miller,CABIOS 4:11-17,1989)或LFASTA (Pearson andLipman,Proc.Natl.Acad.Sci.85:2444-2448,1988)可用于进行序列比较(InternetProgram
1996,W.R.Pearson and the University of Virginia,“fasta20u63”版2.0u63,发行日期1996年12月)。ALIGN比较彼此间的整个序列，而LFASTA比较局部相似性的区域。这些比对工具和它们各自的教程可在因特网上NCSA网站获得。或者，对于多于约30个氨基酸的氨基酸序列的比较，利用被设置为默认参数的默认BLOSUM62矩阵 (空位存在罚分为11，每个残基的空位罚分为1)使用“Blast 2序列”函数。当比对短肽(少于约30个氨基酸)时，应利用被设置为默认参数的PAM30 矩阵(开放空位9，延伸空位1罚分)使用“Blast 2序列”函数进行比对。 BLAST序列比较系统可从例如NCBI网站获得；还参见Altschul etal.J.Mol. Biol.,215:403-10,1990；Gish和States,J.Mol.Biol.,3:266-72,1993；Maddenet al.,Meth.Enzymol.,266:131-41,1996；Altschul et al.,Nucleic Acids Res., 25:3389-402,1997；以及Zhang和Madden,Genome Res.,7:649-56,1997。
受试者：活的多细胞脊椎生物——包括人和非人哺乳动物(如小鼠、大鼠、兔、绵羊、马、牛以及非人灵长类动物)的类别。
转化的：“转化的”细胞是已通过分子生物学技术引入有核酸分子(如异源核酸)的细胞。该术语涵盖通过其核酸分子可以引入此类细胞中的所有技术，包括用病毒载体转染、用质粒载体转化以及通过电穿孔、脂质体转染和粒子枪加速引入裸露的DNA。
疫苗：能够刺激免疫应答的免疫原性材料制品，其被给予用于预防、抑制、改善或治疗感染性或其他类型的疾病。所述免疫原性材料可以包括减毒或灭活的(经杀灭的)微生物(如细菌或病毒)、或来源于其的抗原性蛋白、肽或DNA。减毒病毒是已经修饰以产生更低毒性形式，但仍保留引起针对该毒性形式的抗体和细胞介导的免疫的能力的有毒性的生物体。灭活的(经杀灭的)病毒是已用化学物质、热或其他处理灭活但引起针对生物体的抗体的先前有毒性的生物体。疫苗可能引起预防性的(预防性的或保护性的)和治疗性的应答。给药方法根据所述疫苗而改变，但可包括接种、摄入、吸入或其他给药形式。疫苗可以与佐剂一起给药以加强免疫应答。
III.西尼罗/登革病毒嵌合体
本文公开了嵌合黄病毒，其包括来自WNV的非编码区、非结构蛋白和 C蛋白的至少一部分，以及来自DENV的prM蛋白和E蛋白。下表1-5提供了示例性的西尼罗和登革病毒中具体基因和蛋白质的起始和终止位置。这些序列可充当参照序列并且可以用于鉴定对应于本文中所公开的嵌合核酸或由本文中所公开的嵌合核酸编码的蛋白质中所提及的位置的具体核苷酸或氨基酸位置。例如，基于该信息，本领域普通技术人员可以例如通过比对嵌合体与本文中所提供的一个病毒序列，来鉴定对应于DEN2病毒中E 蛋白氨基酸347的氨基酸位置。
表1.WNV克隆株IC-P991中NCR、结构蛋白以及非结构蛋白的起始和终止位置
表2.DEN1 16007中NCR、结构蛋白以及非结构蛋白的起始和终止位置
表3.DEN2 16681中NCR、结构蛋白以及非结构蛋白的起始和终止位置
表4.DEN3 16562中NCR、结构蛋白以及非结构蛋白的起始和终止位置
表5.DEN4 1036中NCR、结构蛋白以及非结构蛋白的起始和终止位置
在本文中所公开的一些实例中，嵌合体中使用的WNV基因组来源于具体的WNV株，如NY99或KEN-3829。其他WNV株是本领域已知的(参见，例如，Ebel etal.Emerg.Infect.Dis.7:650-653,2001；美国典型培养物保藏中心(ATCC)目录号VR-82、VR-1267、VR-1507、VR-1510)。在具体的实例中，WNV基因组是WN/IC-P991，例如，SEQ ID NO:1或GenBank 登录号AF196835(以引用的方式纳入，如于2014年6月20日包括于 GenBank中，或具有突变，如Kinney et al.,J.Gen.Virol.87:3611-3622,2006 和/或美国专利No.8,715,689中所描述，它们都以引用的方式全文纳入本文)。在一些实例中，修饰WNV基因组序列以例如引入限制性位点以用于克隆目的。这些修饰可以是沉默突变(例如不改变氨基酸序列的核苷酸序列变化)或其可以改变氨基酸序列。
WNV基因组序列是可公开获得的。例如，GenBank登录号AF196835、 AY278441、AF202541、AF404754、AF260967、AY660002、AF481864、 AY268133、AF404757、AY268132、AF260969、AF317203、AY262283、 AY490240、AF260968、AY603654、D00246、M12294、EU068667、AY765264 以及AY277251公开了WNV基因组核酸序列，以上所有登录号都以引用的方式纳入，如于2014年6月20日包括于GenBank中。在其他实例中，WNV 基因组或WNV基因组的非编码区、非结构蛋白和/或C蛋白与可公共获得的WNV基因组序列至少95％、至少96％、至少97％、至少98％或至少99％相同。
在所公开的核酸嵌合体中，DENV基因组来自登革1(DEN1)、登革2 (DEN2)、登革3(DEN3)或登革4(DEN4)病毒。示例性的DENV基因组在本文中公开为SEQ ID NO:3、5、7和9。在一些实例中，所公开的嵌合体的DENV基因组部分包括来自单一DENV基因组的序列，而在其他实例中DENV基因组部分包括来自两个或更多个DENV基因组的序列。DENV 基因组可以是野生型株或减毒(或疫苗)株。在一些实例中，DENV基因组是DEN2(例如野生型DEN2 16681株或减毒DEN-2PDK-53株)、DEN1 (例如野生型DEN1 16007株或减毒DEN1PDK-13株)、DEN3(例如野生型DEN3 16562株或减毒DEN3PGMK-30/FRhL-3)或DEN4(例如野生型 DEN4 1036或减毒DEN4PDK-48)。其他DENV株是本领域已知的(参见，例如美国专利No.5,939,254和6,793,488)。在具体的实例中，DENV基因组是野生型(非减毒)株，例如DEN2 16681(如GenBank登录号U87411，以引用的方式纳入，如于2014年6月20日包括于GenBank中)。在一些实例中，修饰DENV基因组序列以例如引入限制性位点以用于克隆目的。这些修饰可以是沉默突变(例如不改变氨基酸序列的核苷酸序列变化)或其可以改变氨基酸序列。
DENV序列是可公共获得的。例如，GenBank登录号NC_001477、AF180817以及U88536公开了DEN1核酸序列；NC_001474和U87411公开了DEN2核酸序列；NC_001475、AY099336以及AF317645公开了DEN3 核酸序列；并且NC_002640和AF326825公开了DEN4核酸序列，以上所有登录号都以引用的方式纳入，如于2014年6月20日包括于GenBank中。在其他实例中，DENV基因组(或来自DENV基因组的C信号序列、prM 和/或E蛋白)与可公共获得的DENV序列至少95％、至少96％、至少97％、至少98％或至少99％相同。
含有所公开的核酸嵌合体的病毒可以通过在培养中的宿主细胞中复制来容易地产生。产生病毒的方法是本领域公知的(参见，例如Fields Virology, Knipe和Howley,eds.,Lippincott,Williams和Wilkins,2001；Flint et al., Principles of Virology,ASM Press,2000)。宿主细胞系一般经选择以易于用病毒感染或用病毒基因组RNA转染，能够稳定地维持具有未排列序列的外源 RNA，并且具有用于蛋白质或病毒颗粒的有效转录、翻译、翻译后修饰、病毒组装以及分泌的所需细胞组分。另外，细胞通常是可被改造为适于在悬浮培养中生长的具有简单培养基组分要求的那些细胞。在一些实例中，宿主细胞系是被改造为适于在低血清或无血清培养基中生长的哺乳动物细胞系。示例性的合适的宿主细胞系包括Vero(猴)、C6/36(蚊子)、BHK21 (仓鼠)、LLC-MK2(猴)、SK6(猪)、L292(小鼠)、海拉(HeLa)(人类)、 HEK(人类)、2fTGH细胞(人类)、HepG2(人类)以及PDK(狗)细胞。合适的细胞系可以获自美国典型培养物保藏中心(ATCC),马纳萨斯,弗吉尼亚州。
在一些实例中，所公开的嵌合WN/DEN病毒在细胞培养物中比DEN 病毒复制地更快。在一些实例中，由WN/DEN嵌合病毒形成的空斑在细胞培养物(如C6/36或Vero细胞)上比DENV更早地形成(如感染后早至少一天、两天、三天、四天或五天)。在其他实例中，WN/DEN嵌合病毒比 DENV形成更大的空斑，例如比DEN病毒大至少25％到约10倍(如大至少50％、两倍、三倍、四倍、五倍或最高达10倍)的空斑。
本公开内容还提供了具有一个或多个核酸或氨基酸置换、插入、缺失或其组合的WN/DEN嵌合体，以使所得的嵌合体具有改进的特征。在一些实例中，与野生型病毒相比，嵌合体的改进的特征包括(但不限于)增加的病毒效价、增加的复制速率、增加的空斑大小或增加的在细胞培养物中的稳定性。在其他实例中，相比于野生型病毒，嵌合体的改进的特征包括增加在受试者(如小鼠或非人灵长类动物)中的感染力或毒性，或降低在蚊子中的感染力或传播性。
通过包括例如定点诱变或PCR和Ml3引物诱变的标准方法对所公开的嵌合黄病毒的核苷酸序列进行的操纵可用于产生具有改进的特征(如增加的病毒效价或在细胞培养物中的稳定性)的变体。这些技术的细节是公知的。例如，方案提供于Sambrook et al.(ed.),Molecular Cloning:A Laboratory Manual,第2版,第1-3卷,Cold Spring HarborLaboratory Press,Cold Spring Harbor,NY,1989中。最简单的修饰涉及用具有相似的生理化学和/或结构特性的氨基酸置换一个或多个氨基酸。这些所谓的保守性置换有可能对所得蛋白的活性和/或结构具有最小影响。保守性置换一般维持(a)置换区域中多肽主链的结构，例如呈折叠片(sheet)或螺旋构象，(b)靶位点处分子的电荷或疏水性或(c)侧链的体积。以下示出了保守性置换的实例。
通常被预期产生蛋白质特性的最大改变的置换将为非保守性的，例如如下中的改变：(a)亲水性残基(例如丝氨酰基或苏氨酰基)置换(或被置换为)疏水性残基(例如亮氨酰基、异亮氨酰基、苯丙氨酰基、缬氨酰基或丙氨酰基)(或反之亦然)；(b)半胱氨酸或脯氨酸置换(或被置换为) 任何其他残基；(c)具有带正电的侧链的残基(例如赖氨酰基、精氨酰基或组氨酰基)置换(或被置换为)带负电的残基(例如谷氨酰基或天冬氨酰基)(或反之亦然)；或(d)具有大的侧链的残基(例如苯丙氨酸)置换 (或被置换为)不具有侧链的残基(例如甘氨酸)(或反之亦然)。
除了产生所公开的WN/DENV嵌合体的变体的定向诱变以外，产生变体的突变可在细胞培养物中传代时累积，一些具有所需特征。在细胞培养物传代期间在嵌合病毒中累积的核酸和氨基酸置换、插入和/或缺失可容易地通过扩增自分离的病毒种的空斑的病毒的序列分析来确定，并且可以被改造于感染性克隆中以产生具有改进的特征(如达到高效价的复制或在细胞中产生均一大空斑)的WN/DENV嵌合变体。从多个种子或分离的空斑鉴定的一致突变指示了细胞类型中嵌合体的所需置换。先前研究已成功地鉴定出现在细胞培养物中的置换并且将这些置换改造于不同的嵌合病毒构建体中以产生具有改进的特征的嵌合病毒(例如，Huang et al.,J.Virol. 77:11436-11447,2003；Huang et al.,J.Virol.12:7300-7310,2005；；美国专利 No.8,715,689)。
A.具有嵌合prM信号序列的WN/DEN嵌合体
在一些实施方案中，本文中所公开的WN/DEN嵌合核酸包括第一核酸分子，其包括来自西尼罗病毒基因组的5'非编码区、编码C蛋白和非结构蛋白的核酸以及3'非编码区，其中C蛋白包括来自WNV的prM信号序列的一部分(也称为“C(ss)”)和来自DENV基因组的prM信号序列的一部分。所述嵌合体还包括与第一核酸分子可操作地连接的第二核酸分子，其编码来自DENV基因组的prM蛋白和E蛋白的至少一部分。在具体的实例中，编码WNV基因组的prM蛋白和E蛋白的核酸分子用具有来自DENV 基因组的相应序列的分子替换。另外，C蛋白的WNV prM信号序列的一部分用来自DENV的C蛋白的prM信号序列的一部分替换，产生嵌合或“混合”信号序列。这种构建的示例性嵌合体的示意性说明示于图1C中(并且在本文中的一些实例中被称为具有“II型”接合的核酸嵌合体或“II型嵌合体”)。因此，在一些实例中，所述第二核酸包埋在所述第一核酸内，以使嵌合体包括(依次)WNV 5'NCR、包括WNV C(ss)的至少N-末端部分的 WNV C蛋白、C(ss)的DENV C-末端部分、DENV prM蛋白、DENV E蛋白、WNV非结构蛋白(NS1-NS5)以及WNV 3'NCR。
具有II型接合的核酸嵌合体具有长度与天然WNV C(ss)的C(ss)相同的 C(ss)，其为18个氨基酸。C(ss)的5'部分来自WNV基因组并且C(ss)的3' 部分来自DENV基因组。在具有II型接合的核酸嵌合体的具体实例中，C(ss) 包括WNV C(ss)的头六个氨基酸(例如，SEQID NO:2的氨基酸106-111) 和DENV C(ss)的最后12个氨基酸(例如，SEQ ID NO:4、6或8的氨基酸 103-114或SEQ ID NO:10的氨基酸102-113)。例如，II型WN/DEN1嵌合体的C(ss)具有序列GGKTGITMLLMLLPTALA(SEQ ID NO:21)，II型 WN/DEN2嵌合体的C(ss)具有序列GGKTGIGMIIMLIPTVMA(SEQ ID NO: 22)，II型WN/DEN3嵌合体的C(ss)具有序列GGKTGILCLMMMLPATLA (SEQ ID NO:16的氨基酸106-123)，并且II型WN/DEN4嵌合体的C(ss)具有序列GGKTGIITLLCLIPTVMA(SEQ ID NO:23)。具有II型接合的示例性的WN/DEN3嵌合体在本文中以SEQ ID NO:15和16提供。
在其他实例中，II型接合的“杂合”C(ss)(提供了18个氨基酸的C(ss)，但具有WNV和DENV氨基酸)可包括WNV C(ss)的头11-17个氨基酸和 DENV C(ss)的最后1-7个氨基酸。因此，其他II型接合可包括WNV C(ss) 的头11个氨基酸和DENV C(ss)的最后7个氨基酸、WNV C(ss)的头12个氨基酸和DENV C(ss)的最后6个氨基酸等。
在一些实例中，与未经置换的病毒或嵌合体相比，所公开的WN/DEN 嵌合体包括一个或多个核酸置换，其产生提供了所需特征(例如，增加的在细胞培养物(如Vero或C6/36细胞)中的稳定性、复制或病毒效价)的氨基酸置换。示例性的氨基酸置换包括在对应于DEN3的E蛋白氨基酸345 或DEN1、DEN2或DEN4的E蛋白氨基酸347的氨基酸位置处的置换。在一些实例中，氨基酸置换导致在DEN3的第345位氨基酸位置处(His-Leu 变化)或DEN1、DEN2或DEN4的第347位氨基酸位置处(Gln-Leu变化) 存在亮氨酸残基。产生这些置换的示例性的核酸置换提供于下表7中。包括对应于DEN3的E蛋白氨基酸345或DEN1、DEN2或DEN4的E蛋白氨基酸347的氨基酸位置处的置换的示例性II型嵌合体在本文中以SEQ ID NO:15和16的WN/DEN3嵌合体提供。
B.具有登革prM信号序列的WN/DEN嵌合体
在一些实施方案中，本文中所公开的WN/DEN嵌合核酸包括第一核酸分子，其包括来自西尼罗病毒基因组的5'非编码区、编码C蛋白和非结构蛋白的核酸以及3'非编码区，其中C蛋白不包括WNV prM信号序列(例如，嵌合体包括来自DENV基因组的prM信号序列)。所述嵌合体还包括与第一核酸分子可操作地连接的第二核酸分子，其编码来自DENV基因组的prM信号序列以及prM蛋白和E蛋白的至少一部分。在具体的实例中，编码WNV基因组的prM信号序列、prM蛋白以及E蛋白的核酸分子用具有来自DENV基因组的相应序列的分子替换。这种构建的示例性嵌合体的示意性说明示于图1B中(并且本文中的一些实例中称为具有“I型”接合的核酸嵌合体或“I型嵌合体”)。因此，在一些实例中，所述第二核酸包埋在所述第一核酸内，以使嵌合体包括(依次)WNV 5'NCR、不包括C(ss) 的WNV C蛋白、DENV C(ss)、DENV prM蛋白、DENV E蛋白、WNV NS1-NS5以及WNV 3'NCR。
具有I型接合的核酸嵌合体具有来自DENV的prM信号序列(也称为“C(ss)”)，其为14个氨基酸(而非18个氨基酸的WNV C(ss)序列)。具有I 型接合的示例性的WN/DEN嵌合体包括SEQ ID NO:11-14、19和20。
在一些实例中，与未经置换的病毒或嵌合体相比，所公开的WN/DEN 嵌合体包括一个或多个核酸置换，其产生提供了所需特征(例如，增加的在细胞培养物(如Vero或C6/36细胞)中的稳定性、复制或病毒效价)的氨基酸置换。示例性的核酸和氨基酸置换包括示于下表7中的那些。例如， WN/DEN嵌合体可包括一个或多个置换，包括在对应于如下的一个或多个氨基酸处的氨基酸置换：WNV的C蛋白第92位氨基酸位置，DEN1、DEN2 或DEN3的C蛋白第101位氨基酸位置，DEN4的C蛋白第100位氨基酸位置，DEN1、DEN2或DEN3的C蛋白第102位氨基酸位置，DEN4的C 蛋白第101位氨基酸位置；在对应于DEN1、DEN2、DEN3或DEN4的prM 蛋白第22、135、154或155位氨基酸位置的一个或多个氨基酸处的氨基酸置换；在对应于如下的一个或多个氨基酸处的氨基酸置换：DEN1、DEN2、 DEN3或DEN4的E蛋白第171位氨基酸位置；DEN1、DEN2或DEN4的 E蛋白第311位氨基酸位置；DEN3的E蛋白第309位氨基酸位置；DEN1、DEN2或DEN4的E蛋白第347位氨基酸位置；DEN3的E蛋白第345位氨基酸位置；DEN1、DEN2或DEN4的E蛋白第397位氨基酸位置；DEN3 的E蛋白第395位氨基酸位置；DEN1、DEN2或DEN4的E蛋白第417位氨基酸位置；DEN3的E蛋白415氨基酸位置；在WNV的NS3蛋白第71 位氨基酸位置处的置换；和/或在WNV的NS4A蛋白第18位氨基酸位置处的置换。
在一些实例中，两个或更多个置换存在于本文中所公开的嵌合体中。在一个实例中，WN/DEN嵌合体包括在对应于DEN3的E蛋白第201位氨基酸或DEN1、DEN2或DEN4的E蛋白第203位氨基酸的氨基酸位置处的置换，和在对应于DEN4的C蛋白第100位氨基酸位置或DEN1、DEN2 或DEN3的C蛋白第101位氨基酸位置的氨基酸位置处的置换。在另一个实例中，WN/DEN嵌合体包括在对应于DEN1、DEN2、DEN3或DEN4的 prM蛋白氨基酸135的氨基酸位置处的置换，和在对应于DEN4的prM第 154位氨基酸位置或DEN1、DEN2或DEN3的prM第101位氨基酸位置的氨基酸位置处的置换。
在一个具体的实例中，具有I型接合的WN/DEN嵌合体包括在对应于 DEN3的E蛋白氨基酸201或DEN1、DEN2或DEN4的E蛋白氨基酸203 的氨基酸位置处的置换。在一些实例中，氨基酸置换导致在DEN3的E蛋白第201位氨基酸位置(Asn-Asp变化)或DEN1(Glu-Asp变化)、DEN2 (Asn-Asp变化)或DEN4(Lys-Asp变化)的E蛋白第203位氨基酸位置处存在天冬氨酸残基。示例性的I型嵌合体——其包括在对应于DEN3的E 蛋白第201位氨基酸位置或DEN1、DEN2或DEN4的E蛋白第203位氨基酸位置的氨基酸位置处的置换——在本文中以SEQ IDNO:13和14提供 (先前记载于美国专利No.8,715,689中)。在其他实例中，氨基酸置换导致在对应于DEN4的C蛋白第101位氨基酸位置(Thr-Pro变化)或DEN1 (Val-Pro变化)、DEN2(Ala-Pro变化)或DEN3(Ser-Pro变化)的C蛋白第102位氨基酸位置的位置处存在丝氨酸或脯氨酸。示例性的I型嵌合体——其包括在对应于DEN4的C蛋白第101位氨基酸位置或DEN1、DEN2 或DEN3的C蛋白第102位氨基酸位置的氨基酸位置处的置换——在本文中以SEQ IDNO:19和20的WN/DEN4嵌合体提供。
C.具有西尼罗prM信号序列的WN/DEN嵌合体
在一些实施方案中，本文中所公开的WN/DEN嵌合核酸包括第一核酸分子，其包括来自西尼罗病毒基因组的5'非编码区、编码C蛋白和非结构蛋白的核酸以及3'非编码区。所述嵌合体还包括与第一核酸分子可操作地连接的第二核酸分子，其编码来自DENV基因组的prM蛋白和E蛋白的至少一部分。在具体的实例中，编码WNV基因组的prM蛋白和E蛋白的核酸分子用具有来自DENV基因组的相应序列的分子替换。这种构建的示例性嵌合体的示意性说明示于图1D中(并且本文中的一些实例中称为具有“III型”接合的核酸嵌合体或“III型嵌合体”)。因此，在一些实例中，所述第二核酸包埋在所述第一核酸内，以使嵌合体包括(依次)WNV 5'NCR、 WNV C蛋白、DENV prM蛋白、DENV E蛋白、WNV NS1-NS5以及WNV 3'NCR。
具有III型接合的核酸嵌合体具有来自WNV的prM信号序列(也称为“C(ss)”)，其为18个氨基酸(而非14个氨基酸的DENV C(ss)序列)。具有 III型接合的示例性的WN/DEN嵌合体包括SEQ ID NO:17和18。
在一些实例中，与未经置换的病毒或嵌合体相比，所公开的WN/DEN 嵌合体包括一个或多个核酸置换，其产生提供了所需特征(例如，增加的在细胞培养物(如Vero或C6/36细胞)中的稳定性、复制或病毒效价)的氨基酸置换。示例性的氨基酸置换包括在对应于DEN3的E蛋白第345位氨基酸或DEN1、DEN2或DEN4的E蛋白第347位氨基酸的氨基酸位置处的置换。在一些实例中，氨基酸置换导致在DEN3的第345位氨基酸位置 (His-Leu变化)或DEN1(Gln-Leu变化)、DEN2(Val-Leu变化)或DEN4 (Gln-Leu变化)的第347位氨基酸位置处存在亮氨酸残基。产生这些置换的示例性核酸置换提供于下表7中。示例性的III型嵌合体——其包括在对应于DEN3的E蛋白氨基酸345或DEN1、DEN2或DEN4的E蛋白氨基酸347的氨基酸位置处的置换——在本文中以SEQ ID NO:17和18的 WN/DEN3嵌合体提供。
IV.用于引起免疫应答的组合物和方法
本文提供了通过向受试者给予一种或多种包括WN/DEN嵌合核酸(如所公开的核酸嵌合体中的一种或多种)的灭活病毒来引起受试者中的免疫应答的方法。在具体的实例中，所述受试者是人类。将包含WN/DENV核酸嵌合体的灭活病毒用于产生预防或抑制DENV(如DENV1、DENV2、 DENV3或DENV4)感染的免疫应答，并且也可以用于治疗或抑制DENV 感染。
在一些实例中，所述方法还包括选择需要增强对DENV的免疫的受试者。需要增强对DENV的免疫的受试者包括处于DENV感染风险中的受试者、已暴露于一种或多种DENV的受试者以及感染有DENV的受试者。 DENV是地方病的国家或区域的居民或旅客处于感染DENV的风险中。促成感染DENV的风险的其他因素包括区域特征、区域中存在DENV、暴露于蚊子以及缺乏预防性措施(如驱虫剂)。
在一些实例中，将一种、两种、三种、四种或更多种灭活WN/DEN嵌合病毒给药至受试者。如果给药两种或更多种灭活嵌合病毒，其可单独地 (例如，以在短时间段内给药至受试者的单独的免疫原性组合物形式)给药，或其可以基本上同时(例如，以包括两种或更多种灭活嵌合病毒的单一免疫原性组合物形式)给药。在一些实例中，向受试者单独地(例如依次，以任何顺序)或同时(以单一(多价)免疫原性组合物形式)给药灭活的 WN/DEN1、WN/DEN2、WN/DEN3和WN/DEN4病毒。经灭活的WN/DEN 嵌合体可包括本文中所公开的那些和/或美国专利No.8,715,689(以引用的方式全文纳入本文)中所公开的那些的任意组合。在具体的实例中，向受试者(依次或同时)给药四种灭活的WN/DEN嵌合病毒，例如具有I型接合的灭活的WN/DEN1嵌合病毒(如本文中以SEQ ID NO:11和12提供的WN/DEN1嵌合体)、具有I型接合并且在E蛋白第203位氨基酸位置处具 有Asn-Asp置换的灭活的WN/DEN2嵌合病毒(如本文中以SEQ ID NO:13 和14提供的WN/DEN2嵌合体)、具有II型或III型接合并且在E蛋白第345位氨基酸位置处具有His-Leu置换的灭活的WN/DEN3嵌合病毒(如本 文中以SEQ ID NO:15-18提供的WN/DEN3嵌合体)，以及具有I型接合并 且在对应于C蛋白氨基酸101的C蛋白氨基酸位置处具有Thr-Pro置换的 灭活的WN/DEN4嵌合病毒(如本文中以SEQ ID NO:19和20提供的 WN/DEN4嵌合体)。在其他实例中，向受试者(依次或同时)给药两种或三种灭活的WN/DENV嵌合病毒，例如，具有II型或III型接合并且在E 蛋白第345位氨基酸位置处具有His-Leu置换的灭活的WN/DEN3嵌合病毒 (如本文中本文中以SEQ ID NO:15-18提供的WN/DEN3嵌合体)，和具有 I型接合并且在对应于C蛋白氨基酸101的C蛋白氨基酸位置处具有Thr-Pro 置换的灭活的WN/DEN4嵌合病毒(如本文中以SEQ ID NO:19和20提供的WN/DEN4嵌合体)。当灭活病毒被用作减毒活DENV疫苗的加强剂以例如获得针对所有四种DENV血清型的更平衡的免疫时(参见实例7)，给药一种、两种或三种灭活的嵌合病毒可能特别有用。
在一些实例中，使用例如化学灭活、高压灭活、紫外线或γ照射或其任意组合来灭活嵌合病毒。例如，化学灭活包括使病毒暴露于甲醛(例如，福马林)、β-丙内酯、氮丙啶、过氧化氢、有机溶剂、表面活性剂(例如，肌氨酰)或非离子清洁剂(例如，
-X100)或抗坏血酸中的一种或多种，持续足以灭活病毒的时间。在一个实例中，使用氧化剂如过氧化氢灭活病毒，例如，在室温下用约0.05-5％过氧化氢(如约0.1-1％、约0.5-3％、约1-5％)处理约1-24小时(如约1-16小时、约2-12小时、约4-8小时、约1-6小时，例如约1小时、约2小时、约3小时、约4小时、约6小时、约8小时、约12小时、约16小时或约24小时)。参见，例如，WO 2008/039171； Amanna et al.,Nat.Med.18:974-979,2012；Pinto et al.,J.Virol.,87:1926-1936, 2013。对于不同的起始病毒效价或体积，本领域普通技术人员可以确定用于灭活的最优过氧化氢浓度和条件。
在一个具体的非限制性实例中，在约20-37℃(例如，约20-37℃、约 22-30℃、约30-37℃或约室温)下用约0.001-0.5％肌氨酰(如约0.005-0.4％、约0.025-0.2％或约0.01-0.4％肌氨酰，例如，约0.005％、约0.01％、约0.025％、约0.05％、约0.1％、约0.2％、约0.3％、约0.4％或约0.5％肌氨酰)处理病毒(如一种或多种本文中所公开的WN/DENV嵌合体)足够的时间，以灭活所述病毒(如约15分钟到3小时、约30分钟到2小时、约1-2小时或约30分钟到90分钟)。对于其他清洁剂和/或不同的起始病毒效价或体积，本领域普通技术人员可以例如使用实施例5中所描述的方法确定用于灭活的最优清洁剂浓度和条件。在一些实例中，在更低温(如室温)下比在更高温度(如37℃)下使用更长的灭活时间。本领域普通技术人员可以基于处理温度和常规实验确定灭活时间。
在其他实例中，使病毒暴露于紫外线光源(如254nm的UV-C光源) 或辐射源(如钴-60)，持续足以灭活病毒的时间。在一些实例中，使病毒(如一种或多种本文中所公开的WN/DENV嵌合体)暴露于约350-700μW/cm2 (如约350-680pW/cm2、约400-670μW/cm2、约670-685μW/cm2或约350 μW/cm2、约670μW/cm2或约680μW/cm2)UV-254nm约10分钟到2小时 (如约15分钟到1小时、约15-45分钟、约1-2小时、约15分钟、约30分钟、约45分钟、约1小时或更长时间)。在其他实例中，使病毒(如一种或多种本文中所公开的WN/DENV嵌合体)暴露于约0.1-200mW/cm2(如约0.5-5mW/cm2、约1-10mW/cm2、约10-50mW/cm2、约25-100mW/cm2、约100-200mW/cm2，例如，约2mW/cm2、约5mW/cm2、约10mW/cm2、约50mW/cm2、约100mW/cm2、约150mW/cm2或约200mW/cm2)约10 分钟到8小时(如约30分钟到1小时、约1-6小时、约2-4小时、约15分钟、约30分钟、约1小时、约2小时、约3小时、约4小时、约6小时、约8小时)。在一些实例中，在UV处理期间使病毒保持冷却(例如在4℃下或在冰上)。在具体的实例中，将小体积(如低于约1ml)在670μW/cm2下处理15分钟或在350μW/cm2下处理45分钟，并且将更大体积(如约1ml或更大，例如约2-5ml、约1-3ml或更大)在680μW/cm2下处理45分钟或更长时间。对于其他体积或不同的起始病毒效价，本领域普通技术人员可以例如使用实施例5中所描述的方法确定用于灭活的最优UV功率和条件。
在其他实例中，通过光化学灭活来灭活病毒。所述方法包括在光可活化化学物质(如1,5-吲哚叠氮萘(1,5-indonaphthylazide，INA)、4'-氨基甲基-三甲沙林(4'-aminomethyl-trioxsalen，AMT)、8-甲氧基补骨脂素 (8-methoxypsoralen，MOP)、4,5',8-三甲基补骨脂素(TMP)或补骨脂素) 的存在下，使病毒暴露于UV辐射(365nm)。参见，例如Raviprakash et al., Hum Vaccines Immunother.9:2336-2341,2013；Raviv et al.,J.Virol. 82:4612-4619,2008；Sharma et al.,Vaccine29:953-959,2011；Hanson etal., J.Gen.Virol.40:345-358,1978。在具体的实例中，在INA、ANT、MOP、 TMP或补骨脂素的存在下，使病毒(如一种或多种本文中所公开的 WN/DENV嵌合体)暴露于约0.1-200mW/cm2(如约0.1-1mW/cm2，约0.5-5 mW/cm2，约1-100mW/cm2，约100-200mW/cm2，例如，约2mW/cm2，约 100mW/cm2，约145mW/cm2，约180mW/cm2或约200mW/cm2)的UV-365 nm约1分钟到约6小时(如约2-15分钟、约5-30分钟、约15分钟到1小时、约15-45分钟、约1-2小时、约90分钟到4小时、约2-6小时、约2 分钟、约5分钟、约10分钟、约15分钟、约30分钟、约45分钟、约1 小时、约2小时、约4小时、约6小时或更长时间)。本领域普通技术人员可例如使用实施例5中所描述的方法，使用特定化合物、病毒体积或起始病毒效价确定用于灭活的最优UV功率和条件。
已灭活嵌合病毒后，可以纯化灭活病毒。纯化方法包括过滤或渗滤、色谱(例如，尺寸排阻、离子交换或免疫亲和色谱)、密度梯度离心、甘油垫离心或
硫酸盐介质色谱。在其他实例中，在灭活之前纯化嵌合病毒。如果经纯化的病毒被灭活，那么灭活后可以包括额外的纯化步骤，以例如使用例如过滤或缓冲液交换来去除化学灭活剂(如清洁剂)。经纯化的灭活WN/DENV嵌合体的制品可以包括灭活的整个病毒和灭活的病毒样颗粒。
在一些实例中，在灭活之前纯化嵌合体(例如通过聚乙二醇8000 (PEG8000)沉淀和梯度密度离心、甘油垫离心和/或
硫酸盐介质色谱)。例如，必要时，灭活病毒可以进一步通过过滤来纯化以去除灭活试剂。在具体的实例中，灭活后通过过滤、清洁剂去除离心柱(如 MilliporeDetergent-OUTTM试剂盒)、透析或离子交换色谱来去除清洁剂(如肌氨酰)。可以测试细胞培养物中最终产物的感染力(例如如实施例1和2 中所述)、抗原性(例如，通过ELISA；如下文部分VI中所论述)和/或蛋白质浓度(例如通过Bradford或二喹啉甲酸蛋白测定)。
通过通常用于将组合物引入受试者中的任何途径向受试者给药一种或多种包含WN/DEN核酸嵌合体的经纯化的灭活病毒(例如呈药物或免疫原性组合物形式)。给药方法包括(但不限于)真皮内、肌内、腹膜内、肠胃外、静脉内、皮下、阴道、直肠、鼻内、吸入或口服。肠胃外给药(如皮下、静脉内或肌内给药)一般通过注射实现。可注射剂(injectable)可以以常规形式、以液体溶液或悬浮液形式、以适合用于注射前液体中的溶液或悬液的固体形式或以乳液形式制备。可由先前所描述的种类的无菌粉剂、粒剂和片剂来制备注射溶液和悬液。给药可以是全身的或局部的。
以任何合适的方式(如与可药用的载体一起)给予免疫原性组合物。可药用的载体部分地由被给予的具体组合物，以及用以给予所述组合物的具体方法来确定。参见，例如，Remington:The Science and Practice of Pharmacy,The University of the Sciencesin Philadelphia,Editor,Lippincott, Williams,&Wilkins,Philadelphia,PA,第21版(2005)。因此，存在多种本公开内容的药物组合物的合适制剂。
用于肠胃外给药的制剂包括无菌的水性或非水性溶液、悬液以及乳液。非水性溶剂的实例是丙二醇、聚乙二醇、植物油(如橄榄油)以及可注射有机酯(如油酸乙酯)。水性载体包括水、醇/水溶液、乳液或悬液、包括盐水和缓冲介质。肠胃外的载体包括氯化钠溶液、林格氏葡萄糖、葡萄糖以及氯化钠、乳酸林格氏液或不挥发性油。静脉内载体包括流体和营养补充剂、电解质补充剂(如基于林格氏葡萄糖的那些)等。还可以存在防腐剂和其他添加剂，如抗微生物剂、抗氧化剂、螯合剂以及惰性气体等。
在一些实例中，本文中所公开的组合物包括一种或多种佐剂。在其他实例中，佐剂不包括于组合物中，而是在给药本文中所公开的组合物中的一种或多种之前、之后或基本上同时单独地给药至受试者(例如与本文中所公开的组合物组合)。佐剂是与在不存在佐剂下给药抗原相比增加或增强被给予抗原的受试者中的免疫应答的试剂。佐剂的实例是铝盐，如氢氧化铝、磷酸铝、硫酸铝钾或羟基磷酸铝。其他佐剂包括生物佐剂，如细胞因子(例如，IL-2、IL-6、IL-12、RANTES、GM-CSF、TNF-α或IFN-γ)；生长因子(例如GM-CSF或G-CSF)；一个或多个分子，如OX-40L或4-1BBL；免疫刺激的寡核苷酸(例如CpG寡核苷酸)；Toll样受体激动剂(例如，TLR2、 TLR4、TLR7/8或TLR9激动剂)以及细菌脂多糖或其衍生物(如3D-MPL)。其他佐剂包括油与水的乳液、角鲨烯或其他试剂。在一个实例中，所述佐剂是可以名称
(IDEC Pharmaceuticals,圣地亚哥,加利福尼亚州)获得的稳定清洁剂、胶束形成剂和油的混合物。本领域技术人员可以选择待包括于本文中所公开的组合物中或待与本文中所公开的组合物组合给药至受试者的合适的佐剂或佐剂组合。
可通过单剂量或多剂量完成给药。在本公开内容的上下文中给予受试者的剂量应足以随时间推移在受试者中诱导有益的治疗反应，或足以抑制或预防DENV感染。所需剂量根据受试者的物种、年龄、体重以及综合状况、所治疗的感染的严重性、所使用的具体免疫原性组合物以及其给药方式而在各个受试者之间不同。本领域普通技术人员仅使用常规实验即可确定适当的剂量。在一些实例中，给予至受试者的每一种灭活病毒(如呈免疫原性组合物形式)的剂量是约0.1μg到约100μg。例如，免疫原性组合物的剂量可以含有至少0.1μg、至少0.2μg、至少0.25μg、至少0.3μg、至少0.33μg、至少0.4μg、至少0.5μg、至少1.0μg、至少2.0μg、至少3.0μg、至少5.0μg或至少10.0μg(或在0.1与10.0μg之间的任何量)的每一种血清型的病毒。在其他实例中，免疫原性组合物的剂量含有不大于100μg的每一种血清型的病毒，例如，不大于90μg、80μg、75μg、70μg、60μg 或50μg、40μg、30μg、20μg、10μg(或在10与100μg之间的任何量) 的每一种血清型的病毒。
可能需要重复免疫接种以在受试者中产生免疫应答。当以多剂量给药时，在多个时间间隔(如周或月到年)下给药加强剂剂量。在其他实例中，给药一种或多种DEN疫苗(例如，美国专利No.7,094,411中所公开的减毒活重组疫苗)后，将灭活的WN/DEN嵌合病毒用作加强剂。在一个实例中，将DENV疫苗(如减毒活四价DENV组合物)的初次剂量给药至受试者，随后给药至少一次一种或多种(如1、2、3或4种)本文中所公开的灭活 WN/DENV嵌合病毒的加强剂量。在一些实例中，给药初次剂量后，给药加强剂量约14、30、60、90天或更长天数。如果确定必要或有益，那么可以在后续时间点给药额外的(减毒活DENV或灭活WN/DENV嵌合体的) 加强剂。免疫接种方案(如免疫原的量、剂量次数以及给药时机)可以例如通过使用动物模型(如小鼠或非人灵长类动物)、随后通过在人类中的临床测试来通过实验确定。
V.病毒的制备
细胞培养、病毒复制、空斑滴定以及病毒或病毒颗粒纯化的方法是本领域公知的。参见，例如Obijeski et al.,J.Gen.Virol.22:21-33,1974；Beaty et al.,DiagnosticProcedures for Viral,Ricksettial,and Chlamydial Infections,第 189-212页,Lennette et al.(eds),第7版,American Public Health Association, 1995；VirologyMethods Manual,Mahy和Kangro(eds),Academic Press, 1996。
可以使用本领域中已知并且公认的标准方法制备本发明的嵌合病毒。例如，可以将对应于病毒或嵌合病毒的基因组的RNA分子引入到原代细胞、鸡胚或二倍体细胞系中，随后可以从其(或其的上清液)中纯化子代病毒。可以用于产生病毒的另一种方法采用异倍体细胞，如Vero细胞(Yasumura et al.,Nihon Rinsho 21:1201-1215,1963)或C6/36细胞。在这种方法中，将对应于病毒或嵌合病毒的基因组的核酸分子(例如，RNA分子)引入到异倍体细胞中，并且从已培养有细胞的培养基中收集病毒。随后可以将所收集的病毒浓缩(例如，通过PEG 8000沉淀，通过利用使用分子量截止值为例如50-500kDa的过滤器(例如，Amicon超离心过滤器、切向流过滤盒或 Pellicon-2微型超滤盒)的超滤)，在无酚红或FBS的情况下用MEME渗滤，通过添加乳糖配制，并且过滤于无菌容器中。病毒产生方法的细节提供于WO 03/060088中。任选地例如通过密度梯度离心、甘油垫离心和/或
硫酸盐介质色谱来进一步纯化病毒(参见，例如实施例5)。
VI.对黄病毒抗体的检测
本公开内容进一步提供了检测样品(如来自受试者的样品，例如血液样品)中的黄病毒反应性抗体的方法，其包括在可形成抗体/多肽复合物的条件下使样品与本公开内容的嵌合病毒接触；并检测所述复合物的形成，从而检测了样品中的黄病毒抗体。所公开的WN/DEN嵌合体的优势是其比野生型DENV生长地更快，达到更高的效价并且产生更大和更清楚的空斑。因此，本公开内容提供了检测样品中的DENV反应性抗体的方法，其比使用野生型DENV的方法更快速并且更具特异性(参见，例如图4、5A以及 5B)。例如，测定(例如为区分DENV血清型)的特异性可以通过使用所公开的嵌合体改进，所述嵌合体在E蛋白中包括降低抗体交叉反应性的氨基酸置换。
例如，通过使来自受试者的液体或组织样品与本公开内容的嵌合病毒接触并检测至少一种由病毒编码的多肽与抗体的结合，来进行检测样品中的黄病毒反应性抗体的方法。这种方法的液体样品包括可含有抗体的任何生物液体，如脑脊髓液、血液、胆汁血浆、血清、唾液以及尿液。体液的其他可能实例包括痰液、粘液等。
在一个实例中，在空斑减少中和测试(PRNT)或微病灶减少中和测试 (mFRNT)中，使用所公开的嵌合黄病毒在来自受试者的样品中检测DENV 抗体的存在。在PRNT或mFRNT分析中，使样品与由本文中所公开的嵌合黄病毒编码的病毒接触。用病毒-样品混合物接种合适的细胞培养物(如 Vero、C6/36或BHK细胞)以感染细胞。在足以允许空斑或微病灶形成的条件下孵育细胞培养物，并且将形成于接种有嵌合病毒-样品混合物的培养物中的空斑或微病灶数目与形成于对照培养物(如仅接种有病毒的细胞) 中的空斑或微病灶数目进行比较。相比于对照培养物，在接种有嵌合病毒- 样品混合物的细胞培养物中空斑或微病灶数目的减少(例如与对照样品相比较，减少至少50％、60％、70％、80％、90％、95％或99％)指示在样品中存在DENV中和抗体。
酶免疫测定如免疫荧光测定、ELISA以及免疫印迹法可容易地被改造为适于根据本公开内容的方法完成样品中黄病毒抗体的检测。对检测抗体有效的ELISA方法包括，例如：1)将嵌合病毒或病毒颗粒结合到基质上； 2)使经结合的嵌合病毒与含有抗体的液体或组织样品接触；3)使以上物质与结合到可检测部分(例如，辣根过氧化酶或碱性磷酸酶)的二级抗体接触，所述二级抗体与经结合的抗体反应，；4)使以上物质与酶的底物接触；5)使以上物质与染色剂接触；以及6)观测/测量颜色变化或显影。
可检测部分使得能够视觉检测到沉淀或颜色变化，通过显微镜(如显色沉积或荧光)视觉检测，或通过光谱测定、辐射测量等自动化检测。可检测部分的实例包括荧光素、异硫氰酸荧光素、罗丹明、Cy5以及Cy3(用于荧光显微术和/或基于微球体的免疫测定)、辣根过氧化酶(用于光学或电子显微镜和生化检测)、生物素-链霉亲和素(用于光学或电子显微镜)以及碱性磷酸酶(通过颜色变化用于生化检测)。
在竞争性抑制测定中，可用于检测黄病毒抗体的另一种免疫技术使用 mAb来检测与黄病毒多肽特异性反应的抗体。简言之，使样品与结合到基质(例如，96孔板)的本发明的嵌合黄病毒或病毒颗粒接触。彻底洗掉过量样品。随后使经标记(例如，酶联、荧光、放射性等)的mAh与任何先前形成的多肽-抗体复合物接触，并测量mAh结合的量。相对于对照(无抗体)测量抑制mAh结合的量，使得能够检测和测量样品中的抗体。当基于对黄病毒的具体种类或株的mAh结合特异性时，mAh结合抑制的程度可以是用于检测具体黄病毒种类或株的极其特异性的测定。mAb也可用于根据标准方法通过例如免疫荧光测定来直接检测细胞中的黄病毒。
又例如，可以使用微凝集测试来检测样品中黄病毒抗体的存在。简言之，将乳胶珠、红血细胞或其他可凝集颗粒用本公开内容的嵌合黄病毒或病毒颗粒包被，并与样品混合，以使样品中的与抗原特异性反应的抗体与抗原交联，引起凝集。经凝集的抗原-抗体复合物形成用肉眼可见或可通过分光光度计测量的沉淀。
又例如，可以使用基于微球体的免疫测定来检测样品中黄病毒抗体的存在。简言之，将微球体珠用本公开内容的嵌合黄病毒或病毒颗粒包被，并与样品混合，以使样品中的与由病毒编码的抗原特异性反应的抗体结合抗原。使珠结合的病毒-抗体复合物与荧光染料标记的抗物种抗体(如FITC 标记的山羊抗人IgM)反应，并使用微球体读取器(如
仪器)测量。
VII.对候选疫苗功效的评估
本文中所公开的嵌合黄病毒可用于评估候选疫苗(如DENV疫苗候选物)的功效的方法中。先前已开发出许多候选DENV疫苗，如减毒疫苗株 (例如DEN2PDK-53、DEN1PDK-13、DEN3PGMK-30/FRhL-3以及DEN4 PDK-48)和嵌合DENV构建体(参见，例如美国专利No.7,094,411)。但是，由于远交免疫感受态小鼠不死于野生型DENV攻击并且不产生用于测量候选疫苗的保护作用的充分的病毒血症，因此目前没有用于评估候选 DENV疫苗的理想小鼠模型。
在一些实例中，候选DENV疫苗的功效通过用候选疫苗接种受试者(例如，小鼠或非人灵长类动物(如恒河猴))、随后用毒性DENV株攻击来测试。所公开的WN/DENV嵌合体在未经免疫的小鼠中具有毒性和/或产生显著病毒血症，因此它们在先前接种的受试者中可用作攻击剂量。
在一个具体的实施方案中，用候选DENV疫苗(例如，DENV2PDK-53 株)接种一组受试者(如小鼠)。可以通过任何合适方法(包括肠胃外注射 (如腹膜内、皮下或肌内注射)，通过卵内注射于鸟类中、口服，以及通过将病毒(通常携带于药物制剂中)局部施用到气道表面)来进行候选疫苗株病毒的给药。可以通过鼻内给药(例如通过使用鼻内沉积药物制剂的滴管、拭子或吸入器)或通过吸入给药，如通过形成含有呈气溶胶悬液形式的病毒的药物制剂的可吸入颗粒(包括固体颗粒和液体颗粒)，并接着使受试者吸入可吸入颗粒，来进行病毒到气道表面的局部施用。在一个具体的实例中，用载体如磷酸盐缓冲盐水中的候选疫苗病毒腹膜内接种受试者。多次接种(如加强剂)可以由合适时间段(如至少两周、四周、八周、十二周或更长时间)隔开进行。
允许发生基于接种的免疫的合适时间段(如至少两周、四周、八周、十二周或更长时间)后，用毒性或致死剂量的本文中所公开的WN/DEN嵌合体攻击已测试接种有候选疫苗的受试者。攻击剂量通过包括上文那些的任何合适途径给药，并且任选地通过与接种剂量相同或不同的途径给药。攻击剂量后，监测受试者的发病(如发热、皮疹、呕吐、食欲不振、毛糙、驼背、嗜睡、行动不平衡或易颤、脱水、体重减轻或瘫痪征象)或死亡的发生。另外，攻击后从受试者中收集血液用于测量病毒血症水平。与未用候选疫苗接种的一组对照受试者相比，病毒血症水平、发病和/或死亡征象的降低(例如，与对照群体相比，在测试接种的群体中降低至少10％、20％、 30％、40％、50％、60％、70％、80％、90％、95％或99％)指示候选疫苗有效。
提供以下实施例以举例说明某些具体特征和/或实施方案。这些实施例不应被解释为将本公开内容限制在所描述的具体特征或实施方案中。
实施例1
嵌合病毒的构建
本实施例描述了在WNV骨架中包括来自DENV的prM和E基因的嵌合西尼罗/登革病毒的构建。WN/DEN2病毒先前记载于以引用的方式全文纳入本文的美国专利No.8,715,689中。
方法
使用反向遗传学，开发双质粒感染克隆系统来构建针对登革病毒的所有4种血清型(DENV-1到-4)的嵌合WN/DENV。这些嵌合体含有表达 DENV的前膜(prM)和包膜(E)基因的西尼罗病毒(WNV)的复制型载体。prM蛋白是用于在细胞中进行E蛋白加工和病毒包膜组装的重要伴侣蛋白，并且位于衣壳(C)与prM基因之间的肽是用于正确的prM蛋白加工的信号序列(ss)。C(ss)在WNV与DENV之间非常不同。WNV的C(ss) 长度是18个氨基酸，但DENV的C(ss)长度是14个氨基酸。由于C(ss)在 WNV与DENV之间的差异，研究多种接合策略以获得在哺乳动物细胞中具有可接受的生长和稳定性的嵌合体。
嵌合体构建体的初始策略是纳入DENV SS(14个氨基酸)以优化嵌合体中DENV prM的蛋白加工(图1B和表6，I型接合)。该策略先前记载于以引用的方式纳入本文的美国专利No.8,715,689中。使用这种方法，产生来自经转染的C6/36细胞的所有四种血清型的活嵌合病毒，但与细胞培养物或小鼠中的其他三种血清型的嵌合体(一般在p.i.第6-8天>106-107pfu/ml) 相比，WN/DENV-3嵌合体的复制效率显著更低(在p.i.第8天<104pfu/ml)。
为进一步优化WN/DENV嵌合体，测试了额外的嵌合接合策略。测试了WN/DENV-3嵌合体中C(ss)的四个额外的接合位点，并且从四种新接合策略中的三种中回收感染性嵌合体。策略中的两种(II型和III型接合；分别是图1C和1D，以及表6)产生比I型WN/DENV-3嵌合体复制地显著更好并且类似于细胞培养物和小鼠中的其他三种血清型的I型嵌合体的嵌合体。II型接合策略嵌合体含有WNV的N-末端C(ss)的6个氨基酸，之后是 DENV-3的C-末端C(ss)的12个氨基酸。III型策略C(ss)含有来自WNV的 C(ss)的所有18个AA。
将每一种嵌合体的经改造的5'嵌合cDNA克隆(含有5'NCR-C-prM-E) 在体外与3'WNV cDNA克隆(含有 NS1-NS2A/2B-NS3-NS4A/4B-NS5-3'NCR)连接以产生嵌合病毒的全长基因组cDNA。嵌合病毒基因组RNA通过全长cDNA的体外转录产生，并且通过如先前所描述的电穿孔转染到C6/36或Vero细胞中。在转染后第3-7天收集来源于经转染的细胞的嵌合病毒，并且通过在C6/36细胞中传代一次来扩增以产生用于病毒表征的主病毒种。对这些种子进行基因组测序以验证其RNA基因组的正确性。还分析了C6/36和Vero细胞中的病毒的生长动力学以评估其复制效率。在C6/36细胞中这些嵌合体复制地极好并且比野生型DENV显著更快，但一些嵌合病毒在哺乳动物Vero细胞中复制地不佳和/或不稳定。
为进一步改进病毒在Vero细胞中的生长，在次优生长的情况下使嵌合体在Vero细胞中传代最高达十次，以获得使嵌合体在哺乳动物细胞中的生长和基因稳定性改进的细胞适应的突变。在Vero细胞中连续传代后，进行嵌合体的病毒滴定和基因组测序以鉴定使嵌合体在哺乳动物细胞中的适合度和稳定性增强的潜在突变。随后将经确定在Vero细胞适应中有效的特定氨基酸置换通过诱变克隆改造于嵌合构建体中，并且经修饰的嵌合病毒来源于如上文所描述的C6/36细胞。分析这些经修饰的嵌合病毒在Vero细胞中的生长动力学和在小鼠中的感染力，以确认其在哺乳动物细胞中改进的生长以及在小鼠中增强的感染力。还分析了经修饰的嵌合体的基因组序列以确认其在Vero细胞中的基因稳定性。
表6.具有不同类型的接合的WN/DEN嵌合体的结构
阴影方框指示WNV序列；无阴影方框指示DEN序列
结果
WN/DENV-1：对于具有I型接合的WN/DENV-1嵌合体(称为 WN/DENV-1；SEQ ID NO:11和12)，无氨基酸置换是其在这两种细胞类型中良好地复制所必须的，并且其在这两种细胞类型中具有可接受的基因稳定性。因此，直接使用具有I型接合位点的WN/DENV-1，而无进一步的遗传修饰。但是，E蛋白的残基347的突变(Gln到Leu)进一步改进了 WN/DENV-1适合度(表8)。该突变在扩增自Vero细胞的特定WN/DENV-1 病毒种中进化，该病毒种在E蛋白氨基酸106处具有Leu置换(改造为具有Gly-E106-Leu置换的嵌合体)。改造于嵌合体中的Gly-E106-Leu突变通常使嵌合体在Vero细胞中的复制效率更低，因此E347突变似乎对于 WN/DENV-1G106L突变体的适合度比对无G106突变的WN/DENV-1更重要。
WN/DENV-2：先前数据显示具有接合I型策略的WN/DENV-2在C6/36 细胞中而非在Vero细胞中复制良好，但在Vero细胞适应期间在WN/DENV-2 中观察到多个氨基酸置换。进一步的诱变研究显示仅Asn-E203-Asp置换就足以增强嵌合病毒在Vero细胞中的适合度(称为WN/DENV-2E203；SEQ ID NO:13和14)。这种嵌合体详细描述于美国专利No.8,715,689中。其他突变似乎对嵌合体适合度不具有显著作用，但那些突变中的一些的组合也可增加这种嵌合体在Vero细胞中的适合度。
WN/DENV-3：如上文所论述的，使用I型接合策略在任一细胞类型中都不产生稳固的WN/DENV-3嵌合体。在C6/36细胞中，无任何修饰的初始WN/DENV-3比嵌合体的其他三种血清型(通常8或9log10pfu/ml)达到更小的峰效价(<7log10pfu/ml)。当与其他血清型的嵌合体相比较时， WN/DENV-3嵌合体在Vero细胞中还具有最低的生长。在尝试使病毒适应于Vero细胞期间，进化出多个氨基酸突变(表7)。具有这些突变的多种组合(例如，C106/prM22/E395、C106/prM22/prM154、C106/prM154/E395以及C106/prM22/prM154/E395)的WN/DENV-3的若干版本还被改造以改进嵌合体的适合度。尽管在细胞培养物中观测到这些突变的一些有益作用(病毒效价在C6/36细胞培养物中显著增加，但在Vero细胞中仅稍微增加)，但这些置换不足以使嵌合体在Vero细胞中稳定(额外突变将继续从嵌合体的 Vero细胞培养物中进化)。另外，这些修饰中没有一个产生有效感染AG129 小鼠(广泛用于DENV研究的小鼠模型)的令人满意的嵌合体。发现AG129 小鼠对所产生的所有其他血清型的WN/DENV嵌合体高度敏感。
由于使用I型接合策略的WN/DENV-3在细胞培养物中具有更低的复制 /稳定性并且缺乏感染力，因此设计并且产生在C(ss)处具有不同接合策略的四种额外的构建体。这些策略中的两种产生改进的嵌合病毒，WN/DENV-3 B(II型接合)和WN/DENV-3C(III型接合)。来自这两种策略的嵌合体在C6/36和Vero细胞中复制良好，但它们在Vero细胞中基因不稳定。在 WN/DENV-3B(称为WN/DENV-3BE345；SEQ ID NO:15和16)和 WN/DENV-3C(称为WN/DENV-3CE345；SEQ ID NO:17和18)嵌合体中，仅这些嵌合体的一次Vero细胞传代就在E345位置处引起突变(His到 Leu)(表7)。有趣的是，先前鉴定出相同的E345突变对DENV-2/DENV-3 嵌合体的Vero细胞适应是关键的(参见美国专利No.7,094,411)。另外，根据对所有DENV的氨基酸比对，在复制于Vero细胞中的WN/DENV-1E蛋白G106L中进化的E347突变(上文所描述)对应于DENV-3的E345位置。由于E345突变似乎在多种嵌合DENV(尤其是具有DENV-3prM-E基因) 的适合度增强方面极有效，这种置换被纳入具有所有三种接合策略(I、II、III)的WN/DENV-3构建体的最终版本中。对于具有I型接合的构建体 (WN/DENV-3E345)，这种突变仅稍微增强了嵌合体的整体适合度，但嵌合体继续进化，在Vero细胞中具有其他突变。另一方面，WN/DENV-3B和C 构建体中His-E345-Leu突变的纳入成功地使复制于Vero细胞中的嵌合病毒稳定。
WN/DENV-4：C-107残基处的单一置换(Thr到Pro)(表7)被鉴定对于Vero细胞中的WN/DENV-4基因稳定性是重要的。该置换对于C6/36 细胞中病毒的复制或基因稳定性不是关键的。Thr-C107-Pro置换被改造于 WN/DENV-4嵌合体中，称为WN/DENV-4C107(SEQ IDNO:19和20)。 C107(基于嵌合病毒的位置)是在亲本DENV-4株1036的C101处，并且其是使用I型接合策略的嵌合体中C(ss)的第一个DENV-4氨基酸。DENV-4 的C蛋白比DENV的其他三种血清型短一个氨基酸，在所有DENV间的氨基酸序列比对中，将DENV-4的C101与其他三种DENV血清型的C102进行比对。除C107突变以外，还观察到NS4A-18(在嵌合体的WN部分中)处的Gly到Arg突变，其可进一步改进病毒在Vero细胞中的适合度。在Vero 细胞中多次传代后，该突变还是WN/DENV-3中所观察到的多个突变之一 (表7)。
表7.嵌合WN/DEN病毒中的突变
表8.突变对嵌合病毒适合度的影响
"细胞适应的证据包括从细胞培养物中复制的嵌合体的增加的复制效率(生长动力学或空斑大小)、总病毒产率以及基因稳定性。“+”指示突变显示了所述标准中的至少一个。“-”指示突变对于细胞适应来说不是必需的。“Nd”意指未确定；这些突变与其他突变共进化并且其对适合度的贡献还未确定。
实施例2
WN/DENV嵌合体在细胞培养物中的生长特征
本实施例描述了WN/DENV嵌合体在Vero和C6/36细胞培养物中的生长特征。
测试实施例1中所描述的嵌合体(WN/DENV-1、WN/DENV-2E203、 WN/DENV-3CE345以及WN/DENV-4C107)在Vero细胞和C6/36细胞中的复制能力。如细胞中早期的病毒生长所示，这些嵌合体在C6/36和Vero 细胞中比野生型DENV复制地更有效(图2A和2B)。在感染Vero细胞后第二天(d.p.i.)，WN/DENV嵌合体的效价比DENV高约2-3log10(p<0.05) (图2A)。在C6/36细胞培养物的早期时间点中，嵌合体还显示出比DENV 显著更高的效价(p<0.05)(图2B)。在Vero细胞中嵌合体的生长曲线比 DENV的生长曲线早约4-5天趋于平稳，并且在C6/36细胞中早2-3天(表 9)。另外，在C6/36细胞中嵌合体比DENV产生更高的产率(表9)。
表9.嵌合体和DENV在C6/36和Vero细胞中的生长
实施例3
确定WN/DENV嵌合体在小鼠中的毒力和其作为致死攻击病毒用于评估 DENV疫苗的用途
本实施例描述了WN/DENV嵌合体在小鼠中的毒力和所述嵌合体作为致死攻击用于评估候选DENV疫苗的功效的用途。
在3周龄CD-1小鼠和12周龄AG129小鼠中表征嵌合体的毒力(表 10)。通过脑内(i.c.)或腹膜内(i.p.)给药确定WNV、WN/DENV嵌合体和DENV 1-4混合物的50％致死剂量(LD50)。总的来说，在小鼠中 WN/DEN嵌合体比野生型DENV更具有感染力和毒力。
表10.小鼠中的嵌合体毒力
在DENV疫苗功效研究中，评估嵌合体作为AG129小鼠攻击的致死病毒的用途。用单(仅在第0天引发(prime))或双(在第0天引发并在第 30天加强)剂量的tetraDENVax(记载于美国专利No.7,094,411中的四价减毒活重组DEN疫苗)接种3-4周龄AG129小鼠组(n＝32/组)。安慰剂疫苗组在这两天仅接受PBS。随后将每一组的小鼠分成4个子组(n＝8/子组)，并在第120天(第2剂量后3个月)用107pfu的单一血清型的WN/DENV 嵌合体攻击每一个子组。攻击后监测小鼠的发病情况，并将具有发病征象 (如毛糙、驼背、嗜睡、行动不平衡或易颤、脱水、超过10％的体重减轻或瘫痪)的小鼠进行安乐死。通过比较接种组与安慰剂组的存活比率来评估疫苗的保护性功效。在第28天、第60天、第90天、第118天以及第148 天收集小鼠血清。通过微病灶减少中和测试(mFRNT；表11)测试来自每一子组小鼠的血清的针对其各自血清型的中和抗体。
结果显示所有四种血清型的WN/DEN嵌合体对未接种的小鼠(安慰剂组)都是致死的，并且接种有1或2个剂量的减毒活四价疫苗的小鼠完全被保护而免受每一种血清型的WN/DEN病毒攻击(图3A-3D)。还在对大龄Ag 129小鼠(最高达27周龄)的攻击中评估嵌合体，并且在这个年龄组中107pfu的各WN/DEN嵌合体足以在3-7天内引起100％的发病率。由于通过最方便的腹膜内注射，嵌合体对宽年龄范围的AG129小鼠(3到27 周龄)的致死性是均一的，在一周内引起了发病/死亡，因此其可有助于确立简单、灵活以及长期的用于针对所有四种DENV血清型的疫苗或治疗开发的AG129功效模型。
表11.来自TetraDENVax功效研究的中和抗体效价
a接种剂量：0＝第0天和第30天PBS；l＝仅第0天TetraDENVax；2＝第0天和第30天TetraDENVax
b几何平均效价表示70％mFRNT截止值
cNA：不适用。对于血清收集，无小鼠存活。
实施例4
中和测定
本实施例描述了使用WN/DENV嵌合体评估针对DENV感染的中和抗体应答。
针对WN/DEN嵌合体和wt DENV，对一组来自暴露于DENV的单个或多个血清型的患者的人类临床血清进行中和测定。经表征的人类血清的参照组(n＝18)获自美国沃尔特里德陆军研究所(Walter Reed Army Institute of Research)。临床人类血清样品(n＝12)获自Dengue Branch/DVBD/CDC, 圣胡安,波多黎各。从生活在非地方病区域的个体中收集登革未感染的血清样品(n＝4)。
将两倍连续稀释的人类血清样品与特定量的病毒一起在37℃下预孵育 60分钟或在4℃下过夜。将血清/病毒混合物接种于Vero单层上，维持90 分钟吸附，并用含有0.8％琼脂糖(用于空斑减少中和测试(PRNT))或1％羧甲基纤维素(用于微病灶减少中和测试(mFRNT))的培养基覆盖细胞。取决于空斑或微病灶形成所需的时间，在37℃下孵育板1-7天。对于PRNT，用含有1.5％中性红的另一琼脂糖覆盖物覆盖板以显现空斑，并且在接下来1-3天对空斑进行计数。可以在第3-4天对嵌合体的空斑进行计数，并在第 7-10天对wtDENV的空斑进行计数。在mFRNT中，用PBS洗涤板以去除覆盖物并且在-20℃下用丙酮固定1小时。将微病灶用血清型特异性初级Ab 免疫染色，随后用HRP缀合的二级Ab和沉淀底物免疫染色。可以对微斑点染色以在感染嵌合体后24小时计数，并在感染wt DENV后48小时计数。
由于WN/DENV嵌合体复制地更快，因此其比wt DENV更早地产生可见病毒空斑和微病灶。另外，由嵌合体产生的空斑和免疫病灶比来自wt DENV的空斑和免疫病灶更均一并且更清楚(图4、5A以及5B)。因此，在中和测定中使用嵌合体可以潜在地增强测定的效率(更短的持续时间) 和精确性(更精确的空斑或微病灶数目测量)。
相比较于仅感染有病毒的细胞，在接种有病毒-血清混合物的细胞中，空斑或微病灶数目的减少指示在血清中存在中和抗体。中和抗体效价被鉴定为使测试中的病毒空斑数目减少50％、70％或90％的最高血清稀释度(表 12和13)。测试结果显示在所测试的大部分样品中，针对WN/DEN嵌合体的中和效价一般与针对wt DENV(在4倍变异内)的效价一致(表12)。未看到与日本脑炎病毒(JEV)阳性血清的交叉反应性。单血清型血清并不显示出与三种其他DENV血清型的反应性。
表12.使用人类参照组在mFRNT中评估WN/DENV
a中和强度：H＝高，M＝中，L＝低
b效价是对病毒感染的90％中和
表13.使用人类临床血清样品在mFRNT中评估WN/DENV
a效价是对病毒感染的90％中和。除了DENV-未感染的样品，大多数临床样品收集自暴露于多种DENV血清型的患者。
实施例5
灭活WN/DENV嵌合体
本实施例描述了对WN/DENV嵌合体的浓缩/纯化以及对用于灭活 WN/DENV嵌合体的方法的评估和优化。
浓缩/纯化
测试所描述的WN/DENV嵌合体的浓缩和纯化的若干方法。在28℃下用无血清培养基将病毒培养在C6/36细胞中，维持10天或更长天数。在第 5天，去除培养基并且用新鲜培养基替换。从第6天到第10天(或更长天数)，每一天收集培养物上清液以收集病毒，并且用新鲜培养基再培养细胞以用于第二天的收集。通过在4℃下以约15,000xg离心20分钟从细胞碎片中澄清所收集的上清液，然后进行纯化。
第一方法是密度梯度离心，其基于纯化黄病毒的公认的经典方法。使用该方法，终产物是高度纯化的病毒颗粒，但对于WT DENV，病毒产率通常极低(通常<5％)。所述方法耗时、有难度，并且不能理想地适用于大规模病毒制备。首先将病毒经由过滤系统(Amicon超离心过滤器单元， Centricon-70，或切向流过滤系统，其具有MWCO＝50-100kDa膜)或PEG8000沉淀来浓缩，并且接着历经12小时通过30％甘油-45％酒石酸钾梯度以260,000xg超离心一次或两次(第一次3-4小时，收集条带并且在第二梯度上超过12小时)。对于本文中所描述的快速生长的WN/DEN嵌合体，其比野生型DENV达到显著更高的效价，在单一实验室规模纯化批次中使用密度梯度离心获得了比野生型DENV的量整体高50-100倍的嵌合体。
还测试了甘油垫离心。经由30％甘油垫以260,000xg超离心经浓缩的病毒2-3小时。终产物的纯度小于用密度梯度离心所产生的终产物纯度，但所述方法不太耗时、简单且终产率要高得多(25-60％)。
最后，使用
硫酸盐色谱介质来纯化WN/DENV嵌合体。
硫酸盐对包括黄病毒的宽范围病毒具有高亲和力。在具有0-0.1M NaCl的0.01M磷酸钠缓冲液pH7.5或0.5M Tris-HCl pH8.5(吸附缓冲液) 中将病毒样品调节到1-20mg/ml，之后吸附于
硫酸盐柱上。用 5-10柱体积的吸附缓冲液洗涤所述柱，随后用洗脱缓冲液(例如，具有 0.2-1.0M NaCl的0.5M Tris-HCl)洗脱样品。这种方法简单并且更适用于大规模制备，但结果显示终产物仍然比用甘油垫离心所获得的制品含有显著更多的细胞蛋白。通过使用离子盐的多种梯度洗脱样品的进一步优化可以提高产物纯度。而且，这种方法可以作为过程的一部分纳入其他方法中以进一步纯化病毒。例如，为获得更高的纯度，可以在甘油垫离心之前或之后添加该过程。
病毒灭活：
为灭活嵌合WN/DENV嵌合体，测试若干方法。通过UV 254nm辐射在不同功率水平下在冰袋上灭活纯化的嵌合病毒(通常用甘油垫离心纯化)，持续不同时间段。针对感染效价和登革抗原活性，滴定灭活的样品。进一步优化引起全部病毒灭活并保留最高登革抗原活性的UV条件(表14)。鉴定在小样品大小(0.2ml)下在高效价下运行很好的条件(670pW/cm215 分钟或350pW/cm2 45分钟)。对于更大的样品大小(2.4-3.7ml)，680pW/cm2下的更长时间的处理(>45分钟)是完全灭活所需的。
表14.WN/DEN4C107的UV-254nm灭活
还确定的是WN/DENV(最高达4×109pfu/ml)由0.005％肌氨酰在37℃下有效灭活1小时，但仍然保留通过ELISA测量的病毒抗原活性(表15)。更高的最小浓度(≥0.1％)的肌氨酰是灭活具有更高病毒浓度的样品所需的。在0.1％或更高的浓度下，肌氨酰对细胞是有毒的。可以使用超离心过滤器 (例如，Amicon)或Detergent-Out试剂盒(例如，Millipore)来从灭活病毒中去除额外的肌氨酰以降低样品对细胞的毒性。
表15. 37℃下持续1小时对WN/DEN2的肌氨酰灭活
| 肌氨酰浓度 | 病毒效价(pfu/ml) | ELISA活性 |
| 未经处理 | 4.00E+09 | 100％ |
| 0.0005％ | 4.00E+06 | 未进行 |
| 0.005％ | <10 | ≥40％ |
| 0.05％ | <10 | 100％ |
| 0.10％ | 有毒* | 100％ |
| 0.20％ | 有毒* | 100％ |
| 0.40％ | 有毒 | 100％ |
| 未经处理 | 1.20E+11 | 100％ |
| 0.025％ | 310 | 100％ |
| 0.05％ | 10 | 100％ |
| 0.10％ | 有毒* | 100％ |
| 0.20％ | 有毒* | 100％ |
*滴定期间样品中肌氨酰的浓度对细胞有毒。
初步结果显示β-丙内酯(BPL)和过氧化氢还有效地灭活嵌合病毒，但它们还显著降低病毒抗原活性。在4℃下用3％BPL处理48小时或在室温下用0.1％H2O2处理2小时后，测量不到感染力。但是，灭活使得通过 ELISA测量的病毒抗原活性降低超过95％。
实施例6
对小鼠中的灭活WN/DENV嵌合体的评估
本实施例描述了用于评估小鼠中灭活WN/DENV嵌合体的毒力和免疫原性的方法。类似的方法可以用于其他受试者(如非人灵长类动物或人类) 中。
通过实施例5中所描述的方法纯化并灭活是实施例1中所描述的 WN/DENV嵌合体。在第0天和第30天将1-50μg单一血清型的灭活 WN/DENV嵌合体给药至3-4周龄AG129小鼠组。监测小鼠的发病情况，并且将具有发病征象(如毛糙、驼背、嗜睡、行动不平衡或易颤、脱水、超过10％的体重减轻或瘫痪)的小鼠安乐死。通过细胞培养物中的病毒滴定并且通过经免疫的小鼠的存活评估WN/DENV嵌合体的有效灭活。定期 (例如，在第28天、第60天、第90天、第118天和/或第148天，或基于所使用的具体方案的其他合适的天数)收集小鼠血清。通过ELISA测试来自每一子组小鼠的的血清的抗原活性，或通过微病灶减少中和测试来测试针对其各自血清型的中和抗体。选择缺乏发病并诱导最高水平的抗DENV 中和抗体的灭活条件以用作灭活疫苗。在第60天用致死剂量的活 WN/DENV任选地攻击经免疫的小鼠，以确定两种剂量的每一种血清型的灭活疫苗的保护性功效。
实施例7
WN/DENV嵌合体作为灭活DENV疫苗的用途
本实施例描述了用于在AG 129小鼠模型中功效评估经组合的DENV 接种策略的方法。这种经组合的接种策略使用两种剂量的疫苗。一种剂量含有四价减毒活(LA)重组DENV疫苗(参见美国专利No.7,094,411)并且另一种含有用本文中所描述的WN/DEN嵌合体制备的灭活(IA)疫苗。灭活条件如实施例5和6中所描述。类似的方法可以用于其他受试者(如非人灵长类动物或人类)中。
为全面评估IA嵌合体疫苗候选物的潜能，测试以下组合：1)用LA 疫苗引发和加强(2-剂量LA疫苗对照；LA/LA)；2)用IA疫苗引发和加强(2-剂量IA对照；IA/IA)；3)用LA引发并用IA疫苗加强(LA/IA)；4) 用IA引发并用LA疫苗加强(IA/LA)。在第0天，用100μL含有LA四价疫苗(对于每一种血清型为103到105pfu)或每一种灭活病毒的0.1到100μg 范围内的IAWN/DEN嵌合体的PBS腹膜内接种3-4周龄的小鼠组。在第 30天或第60天注射如上文所描述的第二剂量LA或IA。在这两天仅用PBS 注射一组小鼠作为未接种的对照组。
在第90天或第120天，用致死剂量的活WN/DENV嵌合体攻击小鼠。在疫苗功效模型中，已将这些活WN/DEN嵌合体确立为AG 129小鼠的致死攻击病毒(每一种为107pfu)(参见实施例3)。每天监测经攻击的小鼠，持续3-4周，并且将显示疾病征象的小鼠安乐死。在第28天、第58天、第 88天、第118天从动物中收集血液用于免疫原性分析。在实验结束时将对致死攻击后仍存活的小鼠抽血。在56℃下热灭活来自所收集的血液的血清样品30分钟，并且通过ELISA和/或中和测试(例如如实施例4中所描述) 确定血清中的抗体。比较四种接种策略(LA/LA、IA/IA、LA/IA以及IA/LA) 以开发提供最高达100％的免受致死攻击的保护并提供针对所有四种DENV 血清型最平衡的中和抗体应答的优化接种策略。
进行其他小鼠研究以确定单一IA嵌合体血清型或2-3个IA嵌合体血清型的组合作为加强疫苗是否对获得针对DENV的所有4种血清型的经平衡的免疫是更有效的。例如，四价减毒活疫苗可以产生针对DEN1和DEN2 的更高抗体应答，以及针对DEN3和DEN4的更低应答。仅含有WN/DEN 嵌合体的DEN3和DEN4血清型的IA加强剂量可有效地加强针对这两种血清型的抗体应答，并且比含有嵌合体的所有四种血清型的IA加强剂量产生针对所有四种血清型的更平衡的抗体应答。
鉴于本公开内容的原理可应用于许多可能的实施方案，应认识到，所示出的实施方案仅为实例，并且不应被认为是对本发明范围的限制。而是，本发明的范围是由以下的权利要求书限定。因此，申请人要求保护落入这些权利要求的范围和主旨的所有发明。
序列表
<110> 由卫生和人类服务部部长代表的美国政府
Kinney, Claire YH
<120> 嵌合西尼罗/登革病毒和使用方法
<130> 4239-93048-02
<150> US 62/015,265
<151> 2014-06-20
<160> 23
<170> PatentIn version 3.5
<210> 1
<211> 11029
<212> DNA
<213> 西尼罗病毒
<220>
<221> CDS
<222> (97)..(10398)
<400> 1
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Asp Lys Pro Thr Ile Asp Val Lys Met Met Asn Met Glu Ala Ala Asn
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Ser Thr Lys Ala Ala Cys Pro Thr Met Gly Glu Ala His Asn Asp Lys
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Trp Gly Asn Gly Cys Gly Leu Phe Gly Lys Gly Ser Ile Asp Thr Cys
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Ala Lys Phe Ala Cys Ser Thr Lys Ala Ile Gly Arg Thr Ile Leu Lys
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Glu Asn Ile Lys Tyr Glu Val Ala Ile Phe Val His Gly Pro Thr Thr
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Val Glu Ser His Gly Asn Tyr Ser Thr Gln Val Gly Ala Thr Gln Ala
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Gly Arg Phe Ser Ile Thr Pro Ala Ala Pro Ser Tyr Thr Leu Lys Leu
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Asp Thr Asn Ala Tyr Tyr Val Met Thr Val Gly Thr Lys Thr Phe Leu
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Val His Arg Glu Trp Phe Met Asp Leu Asn Leu Pro Trp Ser Ser Ala
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Gly Ser Thr Val Trp Arg Asn Arg Glu Thr Leu Met Glu Phe Glu Glu
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Pro His Ala Thr Lys Gln Ser Val Ile Ala Leu Gly Ser Gln Glu Gly
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Asn Thr Val Lys Leu Thr Ser Gly His Leu Lys Cys Arg Val Lys Met
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Glu Lys Leu Gln Leu Lys Gly Thr Thr Tyr Gly Val Cys Ser Lys Ala
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Phe Lys Phe Leu Gly Thr Pro Ala Asp Thr Gly His Gly Thr Val Val
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Gly Lys Ala Phe Thr Thr Thr Leu Lys Gly Ala Gln Arg Leu Ala Ala
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Leu Gly Asp Thr Ala Trp Asp Phe Gly Ser Val Gly Gly Val Phe Thr
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Ser Val Gly Lys Ala Val His Gln Val Phe Gly Gly Ala Phe Arg Ser
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Thr Thr Val Thr Leu Ser Glu Ser Cys Gly His Arg Gly Pro Ala
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Thr Arg Thr Thr Thr Glu Ser Gly Lys Leu Ile Thr Asp Trp Cys
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Gly Cys Trp Tyr Gly Met Glu Ile Arg Pro Gln Arg His Asp Glu
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Lys Thr Leu Val Gln Ser Gln Val Asn Ala Tyr Asn Ala Asp Met
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Ile Asp Pro Phe Gln Leu Gly Leu Leu Val Val Phe Leu Ala Thr
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Gln Glu Val Leu Arg Lys Arg Trp Thr Ala Lys Ile Ser Met Pro
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Ala Ile Leu Ile Ala Leu Leu Val Leu Val Phe Gly Gly Ile Thr
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Tyr Thr Asp Val Leu Arg Tyr Val Ile Leu Val Gly Ala Ala Phe
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Ala Glu Ser Asn Ser Gly Gly Asp Val Val His Leu Ala Leu Met
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Ala Thr Phe Lys Ile Gln Pro Val Phe Met Val Ala Ser Phe Leu
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Lys Ala Arg Trp Thr Asn Gln Glu Asn Ile Leu Leu Met Leu Ala
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Ala Val Phe Phe Gln Met Ala Tyr Tyr Asp Ala Arg Gln Ile Leu
1255 1260 1265
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Leu Trp Glu Ile Pro Asp Val Leu Asn Ser Leu Ala Val Ala Trp
1270 1275 1280
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Met Ile Leu Arg Ala Ile Thr Phe Thr Thr Thr Ser Asn Val Val
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Val Pro Leu Leu Ala Leu Leu Thr Pro Gly Leu Arg Cys Leu Asn
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Leu Asp Val Tyr Arg Ile Leu Leu Leu Met Val Gly Ile Gly Ser
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Leu Ile Arg Glu Lys Arg Ser Ala Ala Ala Lys Lys Lys Gly Ala
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Ser Leu Leu Cys Leu Ala Leu Ala Ser Thr Gly Leu Phe Asn Pro
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Met Ile Leu Ala Ala Gly Leu Ile Ala Cys Asp Pro Asn Arg Lys
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Arg Gly Trp Pro Ala Thr Glu Val Met Thr Ala Val Gly Leu Met
1375 1380 1385
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Phe Ala Ile Val Gly Gly Leu Ala Glu Leu Asp Ile Asp Ser Met
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Ala Ile Pro Met Thr Ile Ala Gly Leu Met Phe Ala Ala Phe Val
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Ile Ser Gly Lys Ser Thr Asp Met Trp Ile Glu Arg Thr Ala Asp
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Ile Ser Trp Glu Ser Asp Ala Glu Ile Thr Gly Ser Ser Glu Arg
1435 1440 1445
gtt gat gtg cgg ctt gat gat gat gga aac ttc cag ctc atg aat 4485
Val Asp Val Arg Leu Asp Asp Asp Gly Asn Phe Gln Leu Met Asn
1450 1455 1460
gat cca gga gca cct tgg aag ata tgg atg ctc aga atg gtc tgt 4530
Asp Pro Gly Ala Pro Trp Lys Ile Trp Met Leu Arg Met Val Cys
1465 1470 1475
ctc gcg att agt gcg tac acc ccc tgg gca atc ttg ccc tca gta 4575
Leu Ala Ile Ser Ala Tyr Thr Pro Trp Ala Ile Leu Pro Ser Val
1480 1485 1490
gtt gga ttt tgg ata act ctc caa tac aca aag aga gga ggc gtg 4620
Val Gly Phe Trp Ile Thr Leu Gln Tyr Thr Lys Arg Gly Gly Val
1495 1500 1505
ttg tgg gac act ccc tca cca aag gag tac aaa aag ggg gac acg 4665
Leu Trp Asp Thr Pro Ser Pro Lys Glu Tyr Lys Lys Gly Asp Thr
1510 1515 1520
acc acc ggc gtc tac agg atc atg act cgt ggg ctg ctc ggc agt 4710
Thr Thr Gly Val Tyr Arg Ile Met Thr Arg Gly Leu Leu Gly Ser
1525 1530 1535
tat caa gca gga gcg ggc gtg atg gtt gaa ggt gtt ttc cac acc 4755
Tyr Gln Ala Gly Ala Gly Val Met Val Glu Gly Val Phe His Thr
1540 1545 1550
ctt tgg cat aca aca aaa gga gcc gct ttg atg agc gga gag ggc 4800
Leu Trp His Thr Thr Lys Gly Ala Ala Leu Met Ser Gly Glu Gly
1555 1560 1565
cgc ctg gac cca tac tgg ggc agt gtc aag gag gat cga ctt tgt 4845
Arg Leu Asp Pro Tyr Trp Gly Ser Val Lys Glu Asp Arg Leu Cys
1570 1575 1580
tac gga gga ccc tgg aaa ttg cag cac aag tgg aac ggg cag gat 4890
Tyr Gly Gly Pro Trp Lys Leu Gln His Lys Trp Asn Gly Gln Asp
1585 1590 1595
gag gtg cag atg att gtg gtg gaa cct ggc agg aac gtt aag aac 4935
Glu Val Gln Met Ile Val Val Glu Pro Gly Arg Asn Val Lys Asn
1600 1605 1610
gtc cag acg aaa cca ggg gtg ttc aaa aca cct gaa gga gaa atc 4980
Val Gln Thr Lys Pro Gly Val Phe Lys Thr Pro Glu Gly Glu Ile
1615 1620 1625
ggg gcc gtg act ttg gac ttc ccc act gga aca tca ggc tca cca 5025
Gly Ala Val Thr Leu Asp Phe Pro Thr Gly Thr Ser Gly Ser Pro
1630 1635 1640
ata gtg gac aaa aac ggt gat gtg att ggg ctt tat ggc aat gga 5070
Ile Val Asp Lys Asn Gly Asp Val Ile Gly Leu Tyr Gly Asn Gly
1645 1650 1655
gtc ata atg ccc aac ggc tca tac ata agc gcg ata gtg cag ggt 5115
Val Ile Met Pro Asn Gly Ser Tyr Ile Ser Ala Ile Val Gln Gly
1660 1665 1670
gaa agg atg gat gag cca atc cca gcc gga ttc gaa cct gag atg 5160
Glu Arg Met Asp Glu Pro Ile Pro Ala Gly Phe Glu Pro Glu Met
1675 1680 1685
ctg agg aaa aaa cag atc act gta ctg gat ctc cat ccc ggc gcc 5205
Leu Arg Lys Lys Gln Ile Thr Val Leu Asp Leu His Pro Gly Ala
1690 1695 1700
ggt aaa aca agg agg att ctg cca cag atc atc aaa gag gcc ata 5250
Gly Lys Thr Arg Arg Ile Leu Pro Gln Ile Ile Lys Glu Ala Ile
1705 1710 1715
aac aga aga ctg aga aca gcc gtg cta gca cca acc agg gtt gtg 5295
Asn Arg Arg Leu Arg Thr Ala Val Leu Ala Pro Thr Arg Val Val
1720 1725 1730
gct gct gag atg gct gaa gca ctg aga gga ctg ccc atc cgg tac 5340
Ala Ala Glu Met Ala Glu Ala Leu Arg Gly Leu Pro Ile Arg Tyr
1735 1740 1745
cag aca tcc gca gtg ccc aga gaa cat aat gga aat gag att gtt 5385
Gln Thr Ser Ala Val Pro Arg Glu His Asn Gly Asn Glu Ile Val
1750 1755 1760
gat gtc atg tgt cat gct acc ctc acc cac agg ctg atg tct cct 5430
Asp Val Met Cys His Ala Thr Leu Thr His Arg Leu Met Ser Pro
1765 1770 1775
cac agg gtg ccg aac tac aac ctg ttc gtg atg gat gag gct cat 5475
His Arg Val Pro Asn Tyr Asn Leu Phe Val Met Asp Glu Ala His
1780 1785 1790
ttc acc gac cca gct agc att gca gca aga ggt tac att tcc aca 5520
Phe Thr Asp Pro Ala Ser Ile Ala Ala Arg Gly Tyr Ile Ser Thr
1795 1800 1805
aag gtc gag cta ggg gag gcg gcg gca ata ttc atg aca gcc acc 5565
Lys Val Glu Leu Gly Glu Ala Ala Ala Ile Phe Met Thr Ala Thr
1810 1815 1820
cca cca ggc act tca gat cca ttc cca gag tcc aat tca cca att 5610
Pro Pro Gly Thr Ser Asp Pro Phe Pro Glu Ser Asn Ser Pro Ile
1825 1830 1835
tcc gac tta cag act gag atc ccg gat cga gct tgg aac tct gga 5655
Ser Asp Leu Gln Thr Glu Ile Pro Asp Arg Ala Trp Asn Ser Gly
1840 1845 1850
tac gaa tgg atc aca gaa tac acc ggg aag acg gtt tgg ttt gtg 5700
Tyr Glu Trp Ile Thr Glu Tyr Thr Gly Lys Thr Val Trp Phe Val
1855 1860 1865
cct agt gtc aag atg ggg aat gag att gcc ctt tgc cta caa cgt 5745
Pro Ser Val Lys Met Gly Asn Glu Ile Ala Leu Cys Leu Gln Arg
1870 1875 1880
gct gga aag aaa gta gtc caa ttg aac aga aag tcg tac gag acg 5790
Ala Gly Lys Lys Val Val Gln Leu Asn Arg Lys Ser Tyr Glu Thr
1885 1890 1895
gag tac cca aaa tgt aag aac gat gat tgg gac ttt gtt atc aca 5835
Glu Tyr Pro Lys Cys Lys Asn Asp Asp Trp Asp Phe Val Ile Thr
1900 1905 1910
aca gac ata tct gaa atg ggg gct aac ttc aag gcg agc agg gtg 5880
Thr Asp Ile Ser Glu Met Gly Ala Asn Phe Lys Ala Ser Arg Val
1915 1920 1925
att gac agc cgg aag agt gtg aaa cca acc atc ata aca gaa gga 5925
Ile Asp Ser Arg Lys Ser Val Lys Pro Thr Ile Ile Thr Glu Gly
1930 1935 1940
gaa ggg aga gtg atc ctg gga gaa cca tct gca gtg aca gca gct 5970
Glu Gly Arg Val Ile Leu Gly Glu Pro Ser Ala Val Thr Ala Ala
1945 1950 1955
agt gcc gcc cag aga cgt gga cgt atc ggt aga aat ccg tcg caa 6015
Ser Ala Ala Gln Arg Arg Gly Arg Ile Gly Arg Asn Pro Ser Gln
1960 1965 1970
gtt ggt gat gag tac tgt tat ggg ggg cac acg aat gaa gac gac 6060
Val Gly Asp Glu Tyr Cys Tyr Gly Gly His Thr Asn Glu Asp Asp
1975 1980 1985
tcg aac ttc gcc cat tgg act gag gca cga atc atg ctg gac aac 6105
Ser Asn Phe Ala His Trp Thr Glu Ala Arg Ile Met Leu Asp Asn
1990 1995 2000
atc aac atg cca aac gga ctg atc gct caa ttc tac caa cca gag 6150
Ile Asn Met Pro Asn Gly Leu Ile Ala Gln Phe Tyr Gln Pro Glu
2005 2010 2015
cgt gag aag gta tat acc atg gat ggg gaa tac cgg ctc aga gga 6195
Arg Glu Lys Val Tyr Thr Met Asp Gly Glu Tyr Arg Leu Arg Gly
2020 2025 2030
gaa gag aga aaa aac ttt ctg gaa ctg ttg agg act gca gat ctg 6240
Glu Glu Arg Lys Asn Phe Leu Glu Leu Leu Arg Thr Ala Asp Leu
2035 2040 2045
cca gtt tgg ctg gct tac aag gtt gca gcg gct gga gtg tca tac 6285
Pro Val Trp Leu Ala Tyr Lys Val Ala Ala Ala Gly Val Ser Tyr
2050 2055 2060
cac gac cgg agg tgg tgc ttt gat ggt cct agg aca aac aca att 6330
His Asp Arg Arg Trp Cys Phe Asp Gly Pro Arg Thr Asn Thr Ile
2065 2070 2075
tta gaa gac aac aac gaa gtg gaa gtc atc acg aag ctt ggt gaa 6375
Leu Glu Asp Asn Asn Glu Val Glu Val Ile Thr Lys Leu Gly Glu
2080 2085 2090
agg aag att ctg agg ccg cgc tgg att gac gcc agg gtg tac tcg 6420
Arg Lys Ile Leu Arg Pro Arg Trp Ile Asp Ala Arg Val Tyr Ser
2095 2100 2105
gat cac cag gca cta aag gcg ttc aag gac ttc gcc tcg gga aaa 6465
Asp His Gln Ala Leu Lys Ala Phe Lys Asp Phe Ala Ser Gly Lys
2110 2115 2120
cgt tct cag ata ggg ctc att gag gtt ctg gga aag atg cct gag 6510
Arg Ser Gln Ile Gly Leu Ile Glu Val Leu Gly Lys Met Pro Glu
2125 2130 2135
cac ttc atg ggg aag aca tgg gaa gca ctt gac acc atg tac gtt 6555
His Phe Met Gly Lys Thr Trp Glu Ala Leu Asp Thr Met Tyr Val
2140 2145 2150
gtg gcc act gca gag aaa gga gga aga gct cac aga atg gcc ctg 6600
Val Ala Thr Ala Glu Lys Gly Gly Arg Ala His Arg Met Ala Leu
2155 2160 2165
gag gaa ctg cca gat gct ctt cag aca att gcc ttg att gcc tta 6645
Glu Glu Leu Pro Asp Ala Leu Gln Thr Ile Ala Leu Ile Ala Leu
2170 2175 2180
ttg agt gtg atg acc atg gga gta ttc ttc ctc ctc atg cag cgg 6690
Leu Ser Val Met Thr Met Gly Val Phe Phe Leu Leu Met Gln Arg
2185 2190 2195
aag ggc att gga aag ata ggt ttg gga ggc gct gtc ttg gga gtc 6735
Lys Gly Ile Gly Lys Ile Gly Leu Gly Gly Ala Val Leu Gly Val
2200 2205 2210
gcg acc ttt ttc tgt tgg atg gct gaa gtt cca gga acg aag atc 6780
Ala Thr Phe Phe Cys Trp Met Ala Glu Val Pro Gly Thr Lys Ile
2215 2220 2225
gcc gga atg ttg ctg ctc tcc ctt ctc ttg atg att gtg cta att 6825
Ala Gly Met Leu Leu Leu Ser Leu Leu Leu Met Ile Val Leu Ile
2230 2235 2240
cct gag cca gag aag caa cgt tcg cag aca gac aac cag cta gcc 6870
Pro Glu Pro Glu Lys Gln Arg Ser Gln Thr Asp Asn Gln Leu Ala
2245 2250 2255
gtg ttc ctg att tgt gtc atg acc ctt gtg agc gca gtg gca gcc 6915
Val Phe Leu Ile Cys Val Met Thr Leu Val Ser Ala Val Ala Ala
2260 2265 2270
aac gag atg ggt tgg cta gat aag acc aag agt gac ata agc agt 6960
Asn Glu Met Gly Trp Leu Asp Lys Thr Lys Ser Asp Ile Ser Ser
2275 2280 2285
ttg ttt ggg caa aga att gag gtc aag gag aat ttc agc atg gga 7005
Leu Phe Gly Gln Arg Ile Glu Val Lys Glu Asn Phe Ser Met Gly
2290 2295 2300
gag ttt ctt ttg gac ttg agg cct gca aca gcc tgg tca ctg tac 7050
Glu Phe Leu Leu Asp Leu Arg Pro Ala Thr Ala Trp Ser Leu Tyr
2305 2310 2315
gct gtg aca aca gcg gtc ctc act cca ctg cta aag cat ttg atc 7095
Ala Val Thr Thr Ala Val Leu Thr Pro Leu Leu Lys His Leu Ile
2320 2325 2330
acg tca gat tac atc aac acc tca ttg acc tca ata aac gtt cag 7140
Thr Ser Asp Tyr Ile Asn Thr Ser Leu Thr Ser Ile Asn Val Gln
2335 2340 2345
gca agt gca cta ttc aca ctc gcg cga ggc ttc ccc ttc gtc gat 7185
Ala Ser Ala Leu Phe Thr Leu Ala Arg Gly Phe Pro Phe Val Asp
2350 2355 2360
gtt gga gtg tcg gct ctc ctg cta gca gcc gga tgc tgg gga caa 7230
Val Gly Val Ser Ala Leu Leu Leu Ala Ala Gly Cys Trp Gly Gln
2365 2370 2375
gtc acc ctc acc gtt acg gta aca gcg gca aca ctc ctt ttt tgc 7275
Val Thr Leu Thr Val Thr Val Thr Ala Ala Thr Leu Leu Phe Cys
2380 2385 2390
cac tat gcc tac atg gtt ccc ggt tgg caa gct gag gca atg cgc 7320
His Tyr Ala Tyr Met Val Pro Gly Trp Gln Ala Glu Ala Met Arg
2395 2400 2405
tca gcc cag cgg cgg aca gcg gcc gga atc atg aag aac gct gta 7365
Ser Ala Gln Arg Arg Thr Ala Ala Gly Ile Met Lys Asn Ala Val
2410 2415 2420
gtg gat ggc atc gtg gcc acg gac gtc cca gaa tta gag cgc acc 7410
Val Asp Gly Ile Val Ala Thr Asp Val Pro Glu Leu Glu Arg Thr
2425 2430 2435
aca ccc atc atg cag aag aaa gtt gga cag atc atg ctg atc ttg 7455
Thr Pro Ile Met Gln Lys Lys Val Gly Gln Ile Met Leu Ile Leu
2440 2445 2450
gtg tct cta gct gca gta gta gtg aac ccg tct gtg aag aca gta 7500
Val Ser Leu Ala Ala Val Val Val Asn Pro Ser Val Lys Thr Val
2455 2460 2465
cga gaa gcc gga att ttg atc acg gcc gca gcg gtg acg ctt tgg 7545
Arg Glu Ala Gly Ile Leu Ile Thr Ala Ala Ala Val Thr Leu Trp
2470 2475 2480
gag aat gga gca agc tct gtt tgg aac gca aca act gcc atc gga 7590
Glu Asn Gly Ala Ser Ser Val Trp Asn Ala Thr Thr Ala Ile Gly
2485 2490 2495
ctc tgc cac atc atg cgt ggg ggt tgg ttg tca tgt cta tcc ata 7635
Leu Cys His Ile Met Arg Gly Gly Trp Leu Ser Cys Leu Ser Ile
2500 2505 2510
aca tgg aca ctc ata aag aac atg gaa aaa cca gga cta aaa aga 7680
Thr Trp Thr Leu Ile Lys Asn Met Glu Lys Pro Gly Leu Lys Arg
2515 2520 2525
ggt ggg gca aaa gga cgc acc ttg gga gag gtt tgg aaa gaa aga 7725
Gly Gly Ala Lys Gly Arg Thr Leu Gly Glu Val Trp Lys Glu Arg
2530 2535 2540
ctc aac cag atg aca aaa gaa gag ttc act agg tac cgc aaa gag 7770
Leu Asn Gln Met Thr Lys Glu Glu Phe Thr Arg Tyr Arg Lys Glu
2545 2550 2555
gcc atc atc gaa gtc gat cgc tca gcg gca aaa cac gcc agg aaa 7815
Ala Ile Ile Glu Val Asp Arg Ser Ala Ala Lys His Ala Arg Lys
2560 2565 2570
gaa ggc aat gtc act gga ggg cat cca gtc tct agg ggc aca gca 7860
Glu Gly Asn Val Thr Gly Gly His Pro Val Ser Arg Gly Thr Ala
2575 2580 2585
aaa ctg aga tgg ctg gtc gaa cgg agg ttt ctc gaa ccg gtc gga 7905
Lys Leu Arg Trp Leu Val Glu Arg Arg Phe Leu Glu Pro Val Gly
2590 2595 2600
aaa gtg att gac ctt gga tgt gga aga ggc ggt tgg tgt tac tat 7950
Lys Val Ile Asp Leu Gly Cys Gly Arg Gly Gly Trp Cys Tyr Tyr
2605 2610 2615
atg gca acc caa aaa aga gtc caa gaa gtc aga ggg tac aca aag 7995
Met Ala Thr Gln Lys Arg Val Gln Glu Val Arg Gly Tyr Thr Lys
2620 2625 2630
ggc ggt ccc gga cat gaa gag ccc caa cta gtg caa agt tat gga 8040
Gly Gly Pro Gly His Glu Glu Pro Gln Leu Val Gln Ser Tyr Gly
2635 2640 2645
tgg aac att gtc acc atg aag agt gga gtg gat gtg ttc tac aga 8085
Trp Asn Ile Val Thr Met Lys Ser Gly Val Asp Val Phe Tyr Arg
2650 2655 2660
cct tct gag tgt tgt gac acc ctc ctt tgt gac atc gga gag tcc 8130
Pro Ser Glu Cys Cys Asp Thr Leu Leu Cys Asp Ile Gly Glu Ser
2665 2670 2675
tcg tca agt gct gag gtt gaa gag cat agg acg att cgg gtc ctt 8175
Ser Ser Ser Ala Glu Val Glu Glu His Arg Thr Ile Arg Val Leu
2680 2685 2690
gaa atg gtt gag gac tgg ctg cac cga ggg cca agg gaa ttt tgc 8220
Glu Met Val Glu Asp Trp Leu His Arg Gly Pro Arg Glu Phe Cys
2695 2700 2705
gtg aag gtg ctc tgc ccc tac atg ccg aaa gtc ata gag aag atg 8265
Val Lys Val Leu Cys Pro Tyr Met Pro Lys Val Ile Glu Lys Met
2710 2715 2720
gag ctg ctc caa cgc cgg tat ggg ggg gga ctg gtc aga aac cca 8310
Glu Leu Leu Gln Arg Arg Tyr Gly Gly Gly Leu Val Arg Asn Pro
2725 2730 2735
ctc tca cgg aat tcc acg cac gag atg tat tgg gtg agt cga gct 8355
Leu Ser Arg Asn Ser Thr His Glu Met Tyr Trp Val Ser Arg Ala
2740 2745 2750
tca ggc aat gtg gta cat tca gtg aat atg acc agc cag gtg ctc 8400
Ser Gly Asn Val Val His Ser Val Asn Met Thr Ser Gln Val Leu
2755 2760 2765
cta gga aga atg gaa aaa agg acc tgg aag gga ccc caa tac gag 8445
Leu Gly Arg Met Glu Lys Arg Thr Trp Lys Gly Pro Gln Tyr Glu
2770 2775 2780
gaa gat gta aac ttg gga agt gga acc agg gcg gtg gga aaa ccc 8490
Glu Asp Val Asn Leu Gly Ser Gly Thr Arg Ala Val Gly Lys Pro
2785 2790 2795
ctg ctc aac tca gac acc agt aaa atc aag aac agg att gaa cga 8535
Leu Leu Asn Ser Asp Thr Ser Lys Ile Lys Asn Arg Ile Glu Arg
2800 2805 2810
ctc agg cgt gag tac agt tcg acg tgg cac cac gat gag aac cac 8580
Leu Arg Arg Glu Tyr Ser Ser Thr Trp His His Asp Glu Asn His
2815 2820 2825
cca tat aga acc tgg aac tat cac ggc agt tat gat gtg aag ccc 8625
Pro Tyr Arg Thr Trp Asn Tyr His Gly Ser Tyr Asp Val Lys Pro
2830 2835 2840
aca ggc tcc gcc agt tcg ctg gtc aat gga gtg gtc agg ctc ctc 8670
Thr Gly Ser Ala Ser Ser Leu Val Asn Gly Val Val Arg Leu Leu
2845 2850 2855
tca aaa cca tgg gac acc atc acg aat gtt acc acc atg gcc atg 8715
Ser Lys Pro Trp Asp Thr Ile Thr Asn Val Thr Thr Met Ala Met
2860 2865 2870
act gac act act ccc ttc ggg cag cag cga gtg ttc aaa gag aag 8760
Thr Asp Thr Thr Pro Phe Gly Gln Gln Arg Val Phe Lys Glu Lys
2875 2880 2885
gtg gac acg aaa gct cct gaa ccg cca gaa gga gtg aag tac gtg 8805
Val Asp Thr Lys Ala Pro Glu Pro Pro Glu Gly Val Lys Tyr Val
2890 2895 2900
ctc aac gag acc acc aac tgg ttg tgg gcg ttt ttg gcc aga gaa 8850
Leu Asn Glu Thr Thr Asn Trp Leu Trp Ala Phe Leu Ala Arg Glu
2905 2910 2915
aaa cgt ccc aga atg tgc tct cga gag gaa ttc ata aga aag gtc 8895
Lys Arg Pro Arg Met Cys Ser Arg Glu Glu Phe Ile Arg Lys Val
2920 2925 2930
aac agc aat gca gct ttg ggt gcc atg ttt gaa gag cag aat caa 8940
Asn Ser Asn Ala Ala Leu Gly Ala Met Phe Glu Glu Gln Asn Gln
2935 2940 2945
tgg agg agc gcc aga gaa gca gtt gaa gat cca aaa ttt tgg gag 8985
Trp Arg Ser Ala Arg Glu Ala Val Glu Asp Pro Lys Phe Trp Glu
2950 2955 2960
atg gtg gat gag gag cgc gag gca cat ctg cgg ggg gaa tgt cac 9030
Met Val Asp Glu Glu Arg Glu Ala His Leu Arg Gly Glu Cys His
2965 2970 2975
act tgc att tac aac atg atg gga aag aga gag aaa aaa ccc gga 9075
Thr Cys Ile Tyr Asn Met Met Gly Lys Arg Glu Lys Lys Pro Gly
2980 2985 2990
gag ttc gga aag gcc aag gga agc aga gcc att tgg ttc atg tgg 9120
Glu Phe Gly Lys Ala Lys Gly Ser Arg Ala Ile Trp Phe Met Trp
2995 3000 3005
ctc gga gct cgc ttt ctg gag ttc gag gct ctg ggt ttt ctc aat 9165
Leu Gly Ala Arg Phe Leu Glu Phe Glu Ala Leu Gly Phe Leu Asn
3010 3015 3020
gaa gac cac tgg ctt gga aga aag aac tca gga gga ggt gtc gag 9210
Glu Asp His Trp Leu Gly Arg Lys Asn Ser Gly Gly Gly Val Glu
3025 3030 3035
ggc ttg ggc ctc caa aaa ctg ggt tac atc ctg cgt gaa gtt ggc 9255
Gly Leu Gly Leu Gln Lys Leu Gly Tyr Ile Leu Arg Glu Val Gly
3040 3045 3050
acc cgg cct ggg ggc aag atc tat gct gat gac aca gct ggc tgg 9300
Thr Arg Pro Gly Gly Lys Ile Tyr Ala Asp Asp Thr Ala Gly Trp
3055 3060 3065
gac acc cgc atc acg aga gct gac ttg gaa aat gaa gct aag gtg 9345
Asp Thr Arg Ile Thr Arg Ala Asp Leu Glu Asn Glu Ala Lys Val
3070 3075 3080
ctt gag ctg ctt gat ggg gaa cat cgg cgt ctt gcc agg gcc atc 9390
Leu Glu Leu Leu Asp Gly Glu His Arg Arg Leu Ala Arg Ala Ile
3085 3090 3095
att gag ctc acc tat cgt cac aaa gtt gtg aaa gtg atg cgc ccg 9435
Ile Glu Leu Thr Tyr Arg His Lys Val Val Lys Val Met Arg Pro
3100 3105 3110
gct gct gat gga aga acc gtc atg gat gtt atc tcc aga gaa gat 9480
Ala Ala Asp Gly Arg Thr Val Met Asp Val Ile Ser Arg Glu Asp
3115 3120 3125
cag agg ggg agt gga caa gtt gtc acc tac gcc cta aac act ttc 9525
Gln Arg Gly Ser Gly Gln Val Val Thr Tyr Ala Leu Asn Thr Phe
3130 3135 3140
acc aac ctg gcc gtc cag ctg gtg agg atg atg gaa ggg gaa gga 9570
Thr Asn Leu Ala Val Gln Leu Val Arg Met Met Glu Gly Glu Gly
3145 3150 3155
gtg att ggc cca gat gat gtg gag aaa ctc aca aaa ggg aaa gga 9615
Val Ile Gly Pro Asp Asp Val Glu Lys Leu Thr Lys Gly Lys Gly
3160 3165 3170
ccc aaa gtc agg acc tgg ctg ttt gag aat ggg gaa gaa aga ctc 9660
Pro Lys Val Arg Thr Trp Leu Phe Glu Asn Gly Glu Glu Arg Leu
3175 3180 3185
agc cgc atg gct gtc agt gga gat gac tgt gtg gta aag ccc ctg 9705
Ser Arg Met Ala Val Ser Gly Asp Asp Cys Val Val Lys Pro Leu
3190 3195 3200
gac gat cgc ttt gcc acc tcg ctc cac ttc ctc aat gct atg tca 9750
Asp Asp Arg Phe Ala Thr Ser Leu His Phe Leu Asn Ala Met Ser
3205 3210 3215
aag gtt cgc aaa gac atc caa gag tgg aaa ccg tca act gga tgg 9795
Lys Val Arg Lys Asp Ile Gln Glu Trp Lys Pro Ser Thr Gly Trp
3220 3225 3230
tat gat tgg cag cag gtt cca ttt tgc tca aac cat ttc act gaa 9840
Tyr Asp Trp Gln Gln Val Pro Phe Cys Ser Asn His Phe Thr Glu
3235 3240 3245
ttg atc atg aaa gat gga aga aca ctg gtg gtt cca tgc cga gga 9885
Leu Ile Met Lys Asp Gly Arg Thr Leu Val Val Pro Cys Arg Gly
3250 3255 3260
cag gat gaa ttg gta ggc aga gct cgc ata tct cca ggg gcc gga 9930
Gln Asp Glu Leu Val Gly Arg Ala Arg Ile Ser Pro Gly Ala Gly
3265 3270 3275
tgg aac gtc cgc gac act gct tgt ctg gct aag tct tat gcc cag 9975
Trp Asn Val Arg Asp Thr Ala Cys Leu Ala Lys Ser Tyr Ala Gln
3280 3285 3290
atg tgg ctg ctt ctg tac ttc cac aga aga gac ctg cgg ctc atg 10020
Met Trp Leu Leu Leu Tyr Phe His Arg Arg Asp Leu Arg Leu Met
3295 3300 3305
gcc aac gcc att tgc tcc gct gtc cct gtg aat tgg gtc cct acc 10065
Ala Asn Ala Ile Cys Ser Ala Val Pro Val Asn Trp Val Pro Thr
3310 3315 3320
gga aga acc acg tgg tcc atc cat gca gga gga gag tgg atg aca 10110
Gly Arg Thr Thr Trp Ser Ile His Ala Gly Gly Glu Trp Met Thr
3325 3330 3335
aca gag gac atg ttg gag gtc tgg aac cgt gtt tgg ata gag gag 10155
Thr Glu Asp Met Leu Glu Val Trp Asn Arg Val Trp Ile Glu Glu
3340 3345 3350
aat gaa tgg atg gaa gac aaa acc cca gtg gag aaa tgg agt gac 10200
Asn Glu Trp Met Glu Asp Lys Thr Pro Val Glu Lys Trp Ser Asp
3355 3360 3365
gtc cca tat tca gga aaa cga gag gac atc tgg tgt ggc agc ctg 10245
Val Pro Tyr Ser Gly Lys Arg Glu Asp Ile Trp Cys Gly Ser Leu
3370 3375 3380
att ggc aca aga gcc cga gcc acg tgg gca gaa aac atc cag gtg 10290
Ile Gly Thr Arg Ala Arg Ala Thr Trp Ala Glu Asn Ile Gln Val
3385 3390 3395
gct atc aac caa gtc aga gca atc atc gga gat gag aag tat gtg 10335
Ala Ile Asn Gln Val Arg Ala Ile Ile Gly Asp Glu Lys Tyr Val
3400 3405 3410
gat tac atg agt tca cta aag aga tat gaa gac aca act ttg gtt 10380
Asp Tyr Met Ser Ser Leu Lys Arg Tyr Glu Asp Thr Thr Leu Val
3415 3420 3425
gag gac aca gta ctg tag atatttaatc aattgtaaat agacaatata 10428
Glu Asp Thr Val Leu
3430
agtatgcata aaagtgtagt tttatagtag tatttagtgg tgttagtgta aatagttaag10488
aaaattttga ggagaaagtc aggccgggaa gttcccgcca ccggaagttg agtagacggt10548
gctgcctgcg actcaacccc aggaggactg ggtgaacaaa gccgcgaagt gatccatgta10608
agccctcaga accgtctcgg aaggaggacc ccacatgttg taacttcaaa gcccaatgtc10668
agaccacgct acggcgtgct actctgcgga gagtgcagtc tgcgatagtg ccccaggagg10728
actgggttaa caaaggcaaa ccaacgcccc acgcggccct agccccggta atggtgttaa10788
ccagggcgaa aggactagag gttagaggag accccgcggt ttaaagtgca cggcccagcc10848
tggctgaagc tgtaggtcag gggaaggact agaggttagt ggagaccccg tgccacaaaa10908
caccacaaca aaacagcata ttgacacctg ggatagacta ggagatcttc tgctctgcac10968
aaccagccac acggcacagt gcgccgacaa tggtggctgg tggtgcgaga acacaggatc11028
t 11029
<210> 2
<211> 3433
<212> PRT
<213> 西尼罗病毒
<400> 2
Met Ser Lys Lys Pro Gly Gly Pro Gly Lys Ser Arg Ala Val Asn Met
1 5 10 15
Leu Lys Arg Gly Met Pro Arg Val Leu Ser Leu Ile Gly Leu Lys Arg
20 25 30
Ala Met Leu Ser Leu Ile Asp Gly Lys Gly Pro Ile Arg Phe Val Leu
35 40 45
Ala Leu Leu Ala Phe Phe Arg Phe Thr Ala Ile Ala Pro Thr Arg Ala
50 55 60
Val Leu Asp Arg Trp Arg Gly Val Asn Lys Gln Thr Ala Met Lys His
65 70 75 80
Leu Leu Ser Phe Lys Lys Glu Leu Gly Thr Leu Thr Ser Ala Ile Asn
85 90 95
Arg Arg Ser Ser Lys Gln Lys Lys Arg Gly Gly Lys Thr Gly Ile Ala
100 105 110
Val Met Ile Gly Leu Ile Ala Ser Val Gly Ala Val Thr Leu Ser Asn
115 120 125
Phe Gln Gly Lys Val Met Met Thr Val Asn Ala Thr Asp Val Thr Asp
130 135 140
Val Ile Thr Ile Pro Thr Ala Ala Gly Lys Asn Leu Cys Ile Val Arg
145 150 155 160
Ala Met Asp Val Gly Tyr Met Cys Asp Asp Thr Ile Thr Tyr Glu Cys
165 170 175
Pro Val Leu Ser Ala Gly Asn Asp Pro Glu Asp Ile Asp Cys Trp Cys
180 185 190
Thr Lys Ser Ala Val Tyr Val Arg Tyr Gly Arg Cys Thr Lys Thr Arg
195 200 205
His Ser Arg Arg Ser Arg Arg Ser Leu Thr Val Gln Thr His Gly Glu
210 215 220
Ser Thr Leu Ala Asn Lys Lys Gly Ala Trp Met Asp Ser Thr Lys Ala
225 230 235 240
Thr Arg Tyr Leu Val Lys Thr Glu Ser Trp Ile Leu Arg Asn Pro Gly
245 250 255
Tyr Ala Leu Val Ala Ala Val Ile Gly Trp Met Leu Gly Ser Asn Thr
260 265 270
Met Gln Arg Val Val Phe Val Val Leu Leu Leu Leu Val Ala Pro Ala
275 280 285
Tyr Ser Phe Asn Cys Leu Gly Met Ser Asn Arg Asp Phe Leu Glu Gly
290 295 300
Val Ser Gly Ala Thr Trp Val Asp Leu Val Leu Glu Gly Asp Ser Cys
305 310 315 320
Val Thr Ile Met Ser Lys Asp Lys Pro Thr Ile Asp Val Lys Met Met
325 330 335
Asn Met Glu Ala Ala Asn Leu Ala Glu Val Arg Ser Tyr Cys Tyr Leu
340 345 350
Ala Thr Val Ser Asp Leu Ser Thr Lys Ala Ala Cys Pro Thr Met Gly
355 360 365
Glu Ala His Asn Asp Lys Arg Ala Asp Pro Ala Phe Val Cys Arg Gln
370 375 380
Gly Val Val Asp Arg Gly Trp Gly Asn Gly Cys Gly Leu Phe Gly Lys
385 390 395 400
Gly Ser Ile Asp Thr Cys Ala Lys Phe Ala Cys Ser Thr Lys Ala Ile
405 410 415
Gly Arg Thr Ile Leu Lys Glu Asn Ile Lys Tyr Glu Val Ala Ile Phe
420 425 430
Val His Gly Pro Thr Thr Val Glu Ser His Gly Asn Tyr Ser Thr Gln
435 440 445
Val Gly Ala Thr Gln Ala Gly Arg Phe Ser Ile Thr Pro Ala Ala Pro
450 455 460
Ser Tyr Thr Leu Lys Leu Gly Glu Tyr Gly Glu Val Thr Val Asp Cys
465 470 475 480
Glu Pro Arg Ser Gly Ile Asp Thr Asn Ala Tyr Tyr Val Met Thr Val
485 490 495
Gly Thr Lys Thr Phe Leu Val His Arg Glu Trp Phe Met Asp Leu Asn
500 505 510
Leu Pro Trp Ser Ser Ala Gly Ser Thr Val Trp Arg Asn Arg Glu Thr
515 520 525
Leu Met Glu Phe Glu Glu Pro His Ala Thr Lys Gln Ser Val Ile Ala
530 535 540
Leu Gly Ser Gln Glu Gly Ala Leu His Gln Ala Leu Ala Gly Ala Ile
545 550 555 560
Pro Val Glu Phe Ser Ser Asn Thr Val Lys Leu Thr Ser Gly His Leu
565 570 575
Lys Cys Arg Val Lys Met Glu Lys Leu Gln Leu Lys Gly Thr Thr Tyr
580 585 590
Gly Val Cys Ser Lys Ala Phe Lys Phe Leu Gly Thr Pro Ala Asp Thr
595 600 605
Gly His Gly Thr Val Val Leu Glu Leu Gln Tyr Thr Gly Thr Asp Gly
610 615 620
Pro Cys Lys Val Pro Ile Ser Ser Val Ala Ser Leu Asn Asp Leu Thr
625 630 635 640
Pro Val Gly Arg Leu Val Thr Val Asn Pro Phe Val Ser Val Ala Thr
645 650 655
Ala Asn Ala Lys Val Leu Ile Glu Leu Glu Pro Pro Phe Gly Asp Ser
660 665 670
Tyr Ile Val Val Gly Arg Gly Glu Gln Gln Ile Asn His His Trp His
675 680 685
Lys Ser Gly Ser Ser Ile Gly Lys Ala Phe Thr Thr Thr Leu Lys Gly
690 695 700
Ala Gln Arg Leu Ala Ala Leu Gly Asp Thr Ala Trp Asp Phe Gly Ser
705 710 715 720
Val Gly Gly Val Phe Thr Ser Val Gly Lys Ala Val His Gln Val Phe
725 730 735
Gly Gly Ala Phe Arg Ser Leu Phe Gly Gly Met Ser Trp Ile Thr Gln
740 745 750
Gly Leu Leu Gly Ala Leu Leu Leu Trp Met Gly Ile Asn Ala Arg Asp
755 760 765
Arg Ser Ile Ala Leu Thr Phe Leu Ala Val Gly Gly Val Leu Leu Phe
770 775 780
Leu Ser Val Asn Val His Ala Asp Thr Gly Cys Ala Ile Asp Ile Ser
785 790 795 800
Arg Gln Glu Leu Arg Cys Gly Ser Gly Val Phe Ile His Asn Asp Val
805 810 815
Glu Ala Trp Met Asp Arg Tyr Lys Tyr Tyr Pro Glu Thr Pro Gln Gly
820 825 830
Leu Ala Lys Ile Ile Gln Lys Ala His Lys Glu Gly Val Cys Gly Leu
835 840 845
Arg Ser Val Ser Arg Leu Glu His Gln Met Trp Glu Ala Val Lys Asp
850 855 860
Glu Leu Asn Thr Leu Leu Lys Glu Asn Gly Val Asp Leu Ser Val Val
865 870 875 880
Val Glu Lys Gln Glu Gly Met Tyr Lys Ser Ala Pro Lys Arg Leu Thr
885 890 895
Ala Thr Thr Glu Lys Leu Glu Ile Gly Trp Lys Ala Trp Gly Lys Ser
900 905 910
Ile Leu Phe Ala Pro Glu Leu Ala Asn Asn Thr Phe Val Val Asp Gly
915 920 925
Pro Glu Thr Lys Glu Cys Pro Thr Gln Asn Arg Ala Trp Asn Ser Leu
930 935 940
Glu Val Glu Asp Phe Gly Phe Gly Leu Thr Ser Thr Arg Met Phe Leu
945 950 955 960
Lys Val Arg Glu Ser Asn Thr Thr Glu Cys Asp Ser Lys Ile Ile Gly
965 970 975
Thr Ala Val Lys Asn Asn Leu Ala Ile His Ser Asp Leu Ser Tyr Trp
980 985 990
Ile Glu Ser Arg Leu Asn Asp Thr Trp Lys Leu Glu Arg Ala Val Leu
995 1000 1005
Gly Glu Val Lys Ser Cys Thr Trp Pro Glu Thr His Thr Leu Trp
1010 1015 1020
Gly Asp Gly Ile Leu Glu Ser Asp Leu Ile Ile Pro Val Thr Leu
1025 1030 1035
Ala Gly Pro Arg Ser Asn His Asn Arg Arg Pro Gly Tyr Lys Thr
1040 1045 1050
Gln Asn Gln Gly Pro Trp Asp Glu Gly Arg Val Glu Ile Asp Phe
1055 1060 1065
Asp Tyr Cys Pro Gly Thr Thr Val Thr Leu Ser Glu Ser Cys Gly
1070 1075 1080
His Arg Gly Pro Ala Thr Arg Thr Thr Thr Glu Ser Gly Lys Leu
1085 1090 1095
Ile Thr Asp Trp Cys Cys Arg Ser Cys Thr Leu Pro Pro Leu Arg
1100 1105 1110
Tyr Gln Thr Asp Ser Gly Cys Trp Tyr Gly Met Glu Ile Arg Pro
1115 1120 1125
Gln Arg His Asp Glu Lys Thr Leu Val Gln Ser Gln Val Asn Ala
1130 1135 1140
Tyr Asn Ala Asp Met Ile Asp Pro Phe Gln Leu Gly Leu Leu Val
1145 1150 1155
Val Phe Leu Ala Thr Gln Glu Val Leu Arg Lys Arg Trp Thr Ala
1160 1165 1170
Lys Ile Ser Met Pro Ala Ile Leu Ile Ala Leu Leu Val Leu Val
1175 1180 1185
Phe Gly Gly Ile Thr Tyr Thr Asp Val Leu Arg Tyr Val Ile Leu
1190 1195 1200
Val Gly Ala Ala Phe Ala Glu Ser Asn Ser Gly Gly Asp Val Val
1205 1210 1215
His Leu Ala Leu Met Ala Thr Phe Lys Ile Gln Pro Val Phe Met
1220 1225 1230
Val Ala Ser Phe Leu Lys Ala Arg Trp Thr Asn Gln Glu Asn Ile
1235 1240 1245
Leu Leu Met Leu Ala Ala Val Phe Phe Gln Met Ala Tyr Tyr Asp
1250 1255 1260
Ala Arg Gln Ile Leu Leu Trp Glu Ile Pro Asp Val Leu Asn Ser
1265 1270 1275
Leu Ala Val Ala Trp Met Ile Leu Arg Ala Ile Thr Phe Thr Thr
1280 1285 1290
Thr Ser Asn Val Val Val Pro Leu Leu Ala Leu Leu Thr Pro Gly
1295 1300 1305
Leu Arg Cys Leu Asn Leu Asp Val Tyr Arg Ile Leu Leu Leu Met
1310 1315 1320
Val Gly Ile Gly Ser Leu Ile Arg Glu Lys Arg Ser Ala Ala Ala
1325 1330 1335
Lys Lys Lys Gly Ala Ser Leu Leu Cys Leu Ala Leu Ala Ser Thr
1340 1345 1350
Gly Leu Phe Asn Pro Met Ile Leu Ala Ala Gly Leu Ile Ala Cys
1355 1360 1365
Asp Pro Asn Arg Lys Arg Gly Trp Pro Ala Thr Glu Val Met Thr
1370 1375 1380
Ala Val Gly Leu Met Phe Ala Ile Val Gly Gly Leu Ala Glu Leu
1385 1390 1395
Asp Ile Asp Ser Met Ala Ile Pro Met Thr Ile Ala Gly Leu Met
1400 1405 1410
Phe Ala Ala Phe Val Ile Ser Gly Lys Ser Thr Asp Met Trp Ile
1415 1420 1425
Glu Arg Thr Ala Asp Ile Ser Trp Glu Ser Asp Ala Glu Ile Thr
1430 1435 1440
Gly Ser Ser Glu Arg Val Asp Val Arg Leu Asp Asp Asp Gly Asn
1445 1450 1455
Phe Gln Leu Met Asn Asp Pro Gly Ala Pro Trp Lys Ile Trp Met
1460 1465 1470
Leu Arg Met Val Cys Leu Ala Ile Ser Ala Tyr Thr Pro Trp Ala
1475 1480 1485
Ile Leu Pro Ser Val Val Gly Phe Trp Ile Thr Leu Gln Tyr Thr
1490 1495 1500
Lys Arg Gly Gly Val Leu Trp Asp Thr Pro Ser Pro Lys Glu Tyr
1505 1510 1515
Lys Lys Gly Asp Thr Thr Thr Gly Val Tyr Arg Ile Met Thr Arg
1520 1525 1530
Gly Leu Leu Gly Ser Tyr Gln Ala Gly Ala Gly Val Met Val Glu
1535 1540 1545
Gly Val Phe His Thr Leu Trp His Thr Thr Lys Gly Ala Ala Leu
1550 1555 1560
Met Ser Gly Glu Gly Arg Leu Asp Pro Tyr Trp Gly Ser Val Lys
1565 1570 1575
Glu Asp Arg Leu Cys Tyr Gly Gly Pro Trp Lys Leu Gln His Lys
1580 1585 1590
Trp Asn Gly Gln Asp Glu Val Gln Met Ile Val Val Glu Pro Gly
1595 1600 1605
Arg Asn Val Lys Asn Val Gln Thr Lys Pro Gly Val Phe Lys Thr
1610 1615 1620
Pro Glu Gly Glu Ile Gly Ala Val Thr Leu Asp Phe Pro Thr Gly
1625 1630 1635
Thr Ser Gly Ser Pro Ile Val Asp Lys Asn Gly Asp Val Ile Gly
1640 1645 1650
Leu Tyr Gly Asn Gly Val Ile Met Pro Asn Gly Ser Tyr Ile Ser
1655 1660 1665
Ala Ile Val Gln Gly Glu Arg Met Asp Glu Pro Ile Pro Ala Gly
1670 1675 1680
Phe Glu Pro Glu Met Leu Arg Lys Lys Gln Ile Thr Val Leu Asp
1685 1690 1695
Leu His Pro Gly Ala Gly Lys Thr Arg Arg Ile Leu Pro Gln Ile
1700 1705 1710
Ile Lys Glu Ala Ile Asn Arg Arg Leu Arg Thr Ala Val Leu Ala
1715 1720 1725
Pro Thr Arg Val Val Ala Ala Glu Met Ala Glu Ala Leu Arg Gly
1730 1735 1740
Leu Pro Ile Arg Tyr Gln Thr Ser Ala Val Pro Arg Glu His Asn
1745 1750 1755
Gly Asn Glu Ile Val Asp Val Met Cys His Ala Thr Leu Thr His
1760 1765 1770
Arg Leu Met Ser Pro His Arg Val Pro Asn Tyr Asn Leu Phe Val
1775 1780 1785
Met Asp Glu Ala His Phe Thr Asp Pro Ala Ser Ile Ala Ala Arg
1790 1795 1800
Gly Tyr Ile Ser Thr Lys Val Glu Leu Gly Glu Ala Ala Ala Ile
1805 1810 1815
Phe Met Thr Ala Thr Pro Pro Gly Thr Ser Asp Pro Phe Pro Glu
1820 1825 1830
Ser Asn Ser Pro Ile Ser Asp Leu Gln Thr Glu Ile Pro Asp Arg
1835 1840 1845
Ala Trp Asn Ser Gly Tyr Glu Trp Ile Thr Glu Tyr Thr Gly Lys
1850 1855 1860
Thr Val Trp Phe Val Pro Ser Val Lys Met Gly Asn Glu Ile Ala
1865 1870 1875
Leu Cys Leu Gln Arg Ala Gly Lys Lys Val Val Gln Leu Asn Arg
1880 1885 1890
Lys Ser Tyr Glu Thr Glu Tyr Pro Lys Cys Lys Asn Asp Asp Trp
1895 1900 1905
Asp Phe Val Ile Thr Thr Asp Ile Ser Glu Met Gly Ala Asn Phe
1910 1915 1920
Lys Ala Ser Arg Val Ile Asp Ser Arg Lys Ser Val Lys Pro Thr
1925 1930 1935
Ile Ile Thr Glu Gly Glu Gly Arg Val Ile Leu Gly Glu Pro Ser
1940 1945 1950
Ala Val Thr Ala Ala Ser Ala Ala Gln Arg Arg Gly Arg Ile Gly
1955 1960 1965
Arg Asn Pro Ser Gln Val Gly Asp Glu Tyr Cys Tyr Gly Gly His
1970 1975 1980
Thr Asn Glu Asp Asp Ser Asn Phe Ala His Trp Thr Glu Ala Arg
1985 1990 1995
Ile Met Leu Asp Asn Ile Asn Met Pro Asn Gly Leu Ile Ala Gln
2000 2005 2010
Phe Tyr Gln Pro Glu Arg Glu Lys Val Tyr Thr Met Asp Gly Glu
2015 2020 2025
Tyr Arg Leu Arg Gly Glu Glu Arg Lys Asn Phe Leu Glu Leu Leu
2030 2035 2040
Arg Thr Ala Asp Leu Pro Val Trp Leu Ala Tyr Lys Val Ala Ala
2045 2050 2055
Ala Gly Val Ser Tyr His Asp Arg Arg Trp Cys Phe Asp Gly Pro
2060 2065 2070
Arg Thr Asn Thr Ile Leu Glu Asp Asn Asn Glu Val Glu Val Ile
2075 2080 2085
Thr Lys Leu Gly Glu Arg Lys Ile Leu Arg Pro Arg Trp Ile Asp
2090 2095 2100
Ala Arg Val Tyr Ser Asp His Gln Ala Leu Lys Ala Phe Lys Asp
2105 2110 2115
Phe Ala Ser Gly Lys Arg Ser Gln Ile Gly Leu Ile Glu Val Leu
2120 2125 2130
Gly Lys Met Pro Glu His Phe Met Gly Lys Thr Trp Glu Ala Leu
2135 2140 2145
Asp Thr Met Tyr Val Val Ala Thr Ala Glu Lys Gly Gly Arg Ala
2150 2155 2160
His Arg Met Ala Leu Glu Glu Leu Pro Asp Ala Leu Gln Thr Ile
2165 2170 2175
Ala Leu Ile Ala Leu Leu Ser Val Met Thr Met Gly Val Phe Phe
2180 2185 2190
Leu Leu Met Gln Arg Lys Gly Ile Gly Lys Ile Gly Leu Gly Gly
2195 2200 2205
Ala Val Leu Gly Val Ala Thr Phe Phe Cys Trp Met Ala Glu Val
2210 2215 2220
Pro Gly Thr Lys Ile Ala Gly Met Leu Leu Leu Ser Leu Leu Leu
2225 2230 2235
Met Ile Val Leu Ile Pro Glu Pro Glu Lys Gln Arg Ser Gln Thr
2240 2245 2250
Asp Asn Gln Leu Ala Val Phe Leu Ile Cys Val Met Thr Leu Val
2255 2260 2265
Ser Ala Val Ala Ala Asn Glu Met Gly Trp Leu Asp Lys Thr Lys
2270 2275 2280
Ser Asp Ile Ser Ser Leu Phe Gly Gln Arg Ile Glu Val Lys Glu
2285 2290 2295
Asn Phe Ser Met Gly Glu Phe Leu Leu Asp Leu Arg Pro Ala Thr
2300 2305 2310
Ala Trp Ser Leu Tyr Ala Val Thr Thr Ala Val Leu Thr Pro Leu
2315 2320 2325
Leu Lys His Leu Ile Thr Ser Asp Tyr Ile Asn Thr Ser Leu Thr
2330 2335 2340
Ser Ile Asn Val Gln Ala Ser Ala Leu Phe Thr Leu Ala Arg Gly
2345 2350 2355
Phe Pro Phe Val Asp Val Gly Val Ser Ala Leu Leu Leu Ala Ala
2360 2365 2370
Gly Cys Trp Gly Gln Val Thr Leu Thr Val Thr Val Thr Ala Ala
2375 2380 2385
Thr Leu Leu Phe Cys His Tyr Ala Tyr Met Val Pro Gly Trp Gln
2390 2395 2400
Ala Glu Ala Met Arg Ser Ala Gln Arg Arg Thr Ala Ala Gly Ile
2405 2410 2415
Met Lys Asn Ala Val Val Asp Gly Ile Val Ala Thr Asp Val Pro
2420 2425 2430
Glu Leu Glu Arg Thr Thr Pro Ile Met Gln Lys Lys Val Gly Gln
2435 2440 2445
Ile Met Leu Ile Leu Val Ser Leu Ala Ala Val Val Val Asn Pro
2450 2455 2460
Ser Val Lys Thr Val Arg Glu Ala Gly Ile Leu Ile Thr Ala Ala
2465 2470 2475
Ala Val Thr Leu Trp Glu Asn Gly Ala Ser Ser Val Trp Asn Ala
2480 2485 2490
Thr Thr Ala Ile Gly Leu Cys His Ile Met Arg Gly Gly Trp Leu
2495 2500 2505
Ser Cys Leu Ser Ile Thr Trp Thr Leu Ile Lys Asn Met Glu Lys
2510 2515 2520
Pro Gly Leu Lys Arg Gly Gly Ala Lys Gly Arg Thr Leu Gly Glu
2525 2530 2535
Val Trp Lys Glu Arg Leu Asn Gln Met Thr Lys Glu Glu Phe Thr
2540 2545 2550
Arg Tyr Arg Lys Glu Ala Ile Ile Glu Val Asp Arg Ser Ala Ala
2555 2560 2565
Lys His Ala Arg Lys Glu Gly Asn Val Thr Gly Gly His Pro Val
2570 2575 2580
Ser Arg Gly Thr Ala Lys Leu Arg Trp Leu Val Glu Arg Arg Phe
2585 2590 2595
Leu Glu Pro Val Gly Lys Val Ile Asp Leu Gly Cys Gly Arg Gly
2600 2605 2610
Gly Trp Cys Tyr Tyr Met Ala Thr Gln Lys Arg Val Gln Glu Val
2615 2620 2625
Arg Gly Tyr Thr Lys Gly Gly Pro Gly His Glu Glu Pro Gln Leu
2630 2635 2640
Val Gln Ser Tyr Gly Trp Asn Ile Val Thr Met Lys Ser Gly Val
2645 2650 2655
Asp Val Phe Tyr Arg Pro Ser Glu Cys Cys Asp Thr Leu Leu Cys
2660 2665 2670
Asp Ile Gly Glu Ser Ser Ser Ser Ala Glu Val Glu Glu His Arg
2675 2680 2685
Thr Ile Arg Val Leu Glu Met Val Glu Asp Trp Leu His Arg Gly
2690 2695 2700
Pro Arg Glu Phe Cys Val Lys Val Leu Cys Pro Tyr Met Pro Lys
2705 2710 2715
Val Ile Glu Lys Met Glu Leu Leu Gln Arg Arg Tyr Gly Gly Gly
2720 2725 2730
Leu Val Arg Asn Pro Leu Ser Arg Asn Ser Thr His Glu Met Tyr
2735 2740 2745
Trp Val Ser Arg Ala Ser Gly Asn Val Val His Ser Val Asn Met
2750 2755 2760
Thr Ser Gln Val Leu Leu Gly Arg Met Glu Lys Arg Thr Trp Lys
2765 2770 2775
Gly Pro Gln Tyr Glu Glu Asp Val Asn Leu Gly Ser Gly Thr Arg
2780 2785 2790
Ala Val Gly Lys Pro Leu Leu Asn Ser Asp Thr Ser Lys Ile Lys
2795 2800 2805
Asn Arg Ile Glu Arg Leu Arg Arg Glu Tyr Ser Ser Thr Trp His
2810 2815 2820
His Asp Glu Asn His Pro Tyr Arg Thr Trp Asn Tyr His Gly Ser
2825 2830 2835
Tyr Asp Val Lys Pro Thr Gly Ser Ala Ser Ser Leu Val Asn Gly
2840 2845 2850
Val Val Arg Leu Leu Ser Lys Pro Trp Asp Thr Ile Thr Asn Val
2855 2860 2865
Thr Thr Met Ala Met Thr Asp Thr Thr Pro Phe Gly Gln Gln Arg
2870 2875 2880
Val Phe Lys Glu Lys Val Asp Thr Lys Ala Pro Glu Pro Pro Glu
2885 2890 2895
Gly Val Lys Tyr Val Leu Asn Glu Thr Thr Asn Trp Leu Trp Ala
2900 2905 2910
Phe Leu Ala Arg Glu Lys Arg Pro Arg Met Cys Ser Arg Glu Glu
2915 2920 2925
Phe Ile Arg Lys Val Asn Ser Asn Ala Ala Leu Gly Ala Met Phe
2930 2935 2940
Glu Glu Gln Asn Gln Trp Arg Ser Ala Arg Glu Ala Val Glu Asp
2945 2950 2955
Pro Lys Phe Trp Glu Met Val Asp Glu Glu Arg Glu Ala His Leu
2960 2965 2970
Arg Gly Glu Cys His Thr Cys Ile Tyr Asn Met Met Gly Lys Arg
2975 2980 2985
Glu Lys Lys Pro Gly Glu Phe Gly Lys Ala Lys Gly Ser Arg Ala
2990 2995 3000
Ile Trp Phe Met Trp Leu Gly Ala Arg Phe Leu Glu Phe Glu Ala
3005 3010 3015
Leu Gly Phe Leu Asn Glu Asp His Trp Leu Gly Arg Lys Asn Ser
3020 3025 3030
Gly Gly Gly Val Glu Gly Leu Gly Leu Gln Lys Leu Gly Tyr Ile
3035 3040 3045
Leu Arg Glu Val Gly Thr Arg Pro Gly Gly Lys Ile Tyr Ala Asp
3050 3055 3060
Asp Thr Ala Gly Trp Asp Thr Arg Ile Thr Arg Ala Asp Leu Glu
3065 3070 3075
Asn Glu Ala Lys Val Leu Glu Leu Leu Asp Gly Glu His Arg Arg
3080 3085 3090
Leu Ala Arg Ala Ile Ile Glu Leu Thr Tyr Arg His Lys Val Val
3095 3100 3105
Lys Val Met Arg Pro Ala Ala Asp Gly Arg Thr Val Met Asp Val
3110 3115 3120
Ile Ser Arg Glu Asp Gln Arg Gly Ser Gly Gln Val Val Thr Tyr
3125 3130 3135
Ala Leu Asn Thr Phe Thr Asn Leu Ala Val Gln Leu Val Arg Met
3140 3145 3150
Met Glu Gly Glu Gly Val Ile Gly Pro Asp Asp Val Glu Lys Leu
3155 3160 3165
Thr Lys Gly Lys Gly Pro Lys Val Arg Thr Trp Leu Phe Glu Asn
3170 3175 3180
Gly Glu Glu Arg Leu Ser Arg Met Ala Val Ser Gly Asp Asp Cys
3185 3190 3195
Val Val Lys Pro Leu Asp Asp Arg Phe Ala Thr Ser Leu His Phe
3200 3205 3210
Leu Asn Ala Met Ser Lys Val Arg Lys Asp Ile Gln Glu Trp Lys
3215 3220 3225
Pro Ser Thr Gly Trp Tyr Asp Trp Gln Gln Val Pro Phe Cys Ser
3230 3235 3240
Asn His Phe Thr Glu Leu Ile Met Lys Asp Gly Arg Thr Leu Val
3245 3250 3255
Val Pro Cys Arg Gly Gln Asp Glu Leu Val Gly Arg Ala Arg Ile
3260 3265 3270
Ser Pro Gly Ala Gly Trp Asn Val Arg Asp Thr Ala Cys Leu Ala
3275 3280 3285
Lys Ser Tyr Ala Gln Met Trp Leu Leu Leu Tyr Phe His Arg Arg
3290 3295 3300
Asp Leu Arg Leu Met Ala Asn Ala Ile Cys Ser Ala Val Pro Val
3305 3310 3315
Asn Trp Val Pro Thr Gly Arg Thr Thr Trp Ser Ile His Ala Gly
3320 3325 3330
Gly Glu Trp Met Thr Thr Glu Asp Met Leu Glu Val Trp Asn Arg
3335 3340 3345
Val Trp Ile Glu Glu Asn Glu Trp Met Glu Asp Lys Thr Pro Val
3350 3355 3360
Glu Lys Trp Ser Asp Val Pro Tyr Ser Gly Lys Arg Glu Asp Ile
3365 3370 3375
Trp Cys Gly Ser Leu Ile Gly Thr Arg Ala Arg Ala Thr Trp Ala
3380 3385 3390
Glu Asn Ile Gln Val Ala Ile Asn Gln Val Arg Ala Ile Ile Gly
3395 3400 3405
Asp Glu Lys Tyr Val Asp Tyr Met Ser Ser Leu Lys Arg Tyr Glu
3410 3415 3420
Asp Thr Thr Leu Val Glu Asp Thr Val Leu
3425 3430
<210> 3
<211> 10735
<212> DNA
<213> I型登革病毒
<220>
<221> CDS
<222> (95)..(10273)
<400> 3
agttgttagt ctacgtggac cgacaagaac agtttcgaat cggaagcttg cttaacgtag 60
ttctaacagt tttttattag agagcagatc tctg atg atc aac caa cga aaa aag 115
Met Ile Asn Gln Arg Lys Lys
1 5
acg ggt cga ccg tct ttc aat atg ctg aaa cgc gcg aga aac cgc gtg 163
Thr Gly Arg Pro Ser Phe Asn Met Leu Lys Arg Ala Arg Asn Arg Val
10 15 20
tca act gtt tca cag ttg gcg aag aga ttc tca aaa gga ttg ctc tca 211
Ser Thr Val Ser Gln Leu Ala Lys Arg Phe Ser Lys Gly Leu Leu Ser
25 30 35
ggc caa gga ccc atg aaa ttg gtg atg gct ttc ata gca ttc tta aga 259
Gly Gln Gly Pro Met Lys Leu Val Met Ala Phe Ile Ala Phe Leu Arg
40 45 50 55
ttt cta gcc ata ccc cca aca gca gga att ttg gct aga tgg ggc tca 307
Phe Leu Ala Ile Pro Pro Thr Ala Gly Ile Leu Ala Arg Trp Gly Ser
60 65 70
ttc aag aag aat gga gcg att aaa gtg tta cgg ggt ttc aag aga gaa 355
Phe Lys Lys Asn Gly Ala Ile Lys Val Leu Arg Gly Phe Lys Arg Glu
75 80 85
atc tca aac atg cta aac ata atg aac agg agg aaa aga tcc gtg acc 403
Ile Ser Asn Met Leu Asn Ile Met Asn Arg Arg Lys Arg Ser Val Thr
90 95 100
atg ctc ctt atg ctg ctg ccc aca gcc ctg gcg ttc cat ctg acg aca 451
Met Leu Leu Met Leu Leu Pro Thr Ala Leu Ala Phe His Leu Thr Thr
105 110 115
cga ggg gga gag ccg cat atg ata gtt agc aag cag gaa aga gga aag 499
Arg Gly Gly Glu Pro His Met Ile Val Ser Lys Gln Glu Arg Gly Lys
120 125 130 135
tca ctt ttg ttc aag acc tct gca ggt gtc aac atg tgc acc ctc att 547
Ser Leu Leu Phe Lys Thr Ser Ala Gly Val Asn Met Cys Thr Leu Ile
140 145 150
gcg atg gat ttg gga gag ttg tgt gag gac acg atg acc tac aaa tgc 595
Ala Met Asp Leu Gly Glu Leu Cys Glu Asp Thr Met Thr Tyr Lys Cys
155 160 165
ccc cgg atc act gag gcg gaa cca gat gac gtt gac tgt tgg tgc aat 643
Pro Arg Ile Thr Glu Ala Glu Pro Asp Asp Val Asp Cys Trp Cys Asn
170 175 180
gcc acg gac aca tgg gtg acc tat gga acg tgc tct caa act ggc gaa 691
Ala Thr Asp Thr Trp Val Thr Tyr Gly Thr Cys Ser Gln Thr Gly Glu
185 190 195
cac cga cga gac aaa cgt tcc gtc gca ttg gcc cca cac gtg ggg ctt 739
His Arg Arg Asp Lys Arg Ser Val Ala Leu Ala Pro His Val Gly Leu
200 205 210 215
ggc cta gaa aca aga gcc gaa acg tgg atg tcc tct gaa ggt gct tgg 787
Gly Leu Glu Thr Arg Ala Glu Thr Trp Met Ser Ser Glu Gly Ala Trp
220 225 230
aaa cag ata caa aaa gta gag act tgg gct ctg aga cat cca gga ttc 835
Lys Gln Ile Gln Lys Val Glu Thr Trp Ala Leu Arg His Pro Gly Phe
235 240 245
acg gtg ata gcc ctt ttt cta gca cat gcc ata gga aca tcc atc acc 883
Thr Val Ile Ala Leu Phe Leu Ala His Ala Ile Gly Thr Ser Ile Thr
250 255 260
cag aaa ggg atc att ttc att ttg ctg atg ctg gta aca cca tct atg 931
Gln Lys Gly Ile Ile Phe Ile Leu Leu Met Leu Val Thr Pro Ser Met
265 270 275
gcc atg cga tgc gtg gga ata ggc aac aga gac ttc gtg gaa gga ctg 979
Ala Met Arg Cys Val Gly Ile Gly Asn Arg Asp Phe Val Glu Gly Leu
280 285 290 295
tca gga gca aca tgg gtg gat gtg gta ctg gag cat gga agt tgc gtc 1027
Ser Gly Ala Thr Trp Val Asp Val Val Leu Glu His Gly Ser Cys Val
300 305 310
acc acc atg gca aaa aac aaa cca aca ctg gac att gaa ctc ttg aag 1075
Thr Thr Met Ala Lys Asn Lys Pro Thr Leu Asp Ile Glu Leu Leu Lys
315 320 325
acg gag gtc aca aac cct gca gtt ctg cgt aaa ttg tgc att gaa gct 1123
Thr Glu Val Thr Asn Pro Ala Val Leu Arg Lys Leu Cys Ile Glu Ala
330 335 340
aaa ata tca aac acc acc acc gat tcg aga tgt cca aca caa gga gaa 1171
Lys Ile Ser Asn Thr Thr Thr Asp Ser Arg Cys Pro Thr Gln Gly Glu
345 350 355
gcc aca ctg gtg gaa gaa caa gac gcg aac ttt gtg tgc cga cga acg 1219
Ala Thr Leu Val Glu Glu Gln Asp Ala Asn Phe Val Cys Arg Arg Thr
360 365 370 375
ttc gtg gac aga ggc tgg ggc aat ggc tgt ggg cta ttc gga aaa ggt 1267
Phe Val Asp Arg Gly Trp Gly Asn Gly Cys Gly Leu Phe Gly Lys Gly
380 385 390
agt cta ata acg tgt gcc aag ttt aag tgt gtg aca aaa cta gaa gga 1315
Ser Leu Ile Thr Cys Ala Lys Phe Lys Cys Val Thr Lys Leu Glu Gly
395 400 405
aag ata gtt caa tat gaa aac cta aaa tat tca gtg ata gtc acc gtc 1363
Lys Ile Val Gln Tyr Glu Asn Leu Lys Tyr Ser Val Ile Val Thr Val
410 415 420
cac act gga gat cag cac cag gtg gga aat gag act aca gaa cat gga 1411
His Thr Gly Asp Gln His Gln Val Gly Asn Glu Thr Thr Glu His Gly
425 430 435
aca act gca acc ata aca cct caa gct cct acg tcg gaa ata cag ctg 1459
Thr Thr Ala Thr Ile Thr Pro Gln Ala Pro Thr Ser Glu Ile Gln Leu
440 445 450 455
acc gac tac gga acc ctt aca tta gat tgt tca cct agg aca ggg cta 1507
Thr Asp Tyr Gly Thr Leu Thr Leu Asp Cys Ser Pro Arg Thr Gly Leu
460 465 470
gat ttt aac gag atg gtg ttg ctg aca atg aaa gaa aga tca tgg ctt 1555
Asp Phe Asn Glu Met Val Leu Leu Thr Met Lys Glu Arg Ser Trp Leu
475 480 485
gtc cac aaa caa tgg ttt cta gac tta cca ctg cct tgg acc tct ggg 1603
Val His Lys Gln Trp Phe Leu Asp Leu Pro Leu Pro Trp Thr Ser Gly
490 495 500
gct tca aca tcc caa gag act tgg aac aga caa gat tta ctg gtc aca 1651
Ala Ser Thr Ser Gln Glu Thr Trp Asn Arg Gln Asp Leu Leu Val Thr
505 510 515
ttt aag aca gct cat gca aag aag cag gaa gta gtc gta cta gga tca 1699
Phe Lys Thr Ala His Ala Lys Lys Gln Glu Val Val Val Leu Gly Ser
520 525 530 535
caa gaa gga gca atg cac act gcg ctg act gga gcg aca gaa atc caa 1747
Gln Glu Gly Ala Met His Thr Ala Leu Thr Gly Ala Thr Glu Ile Gln
540 545 550
acg tca gga acg aca aca att ttc gca gga cac cta aaa tgc aga cta 1795
Thr Ser Gly Thr Thr Thr Ile Phe Ala Gly His Leu Lys Cys Arg Leu
555 560 565
aaa atg gac aaa cta act tta aaa ggg atg tca tat gtg atg tgc aca 1843
Lys Met Asp Lys Leu Thr Leu Lys Gly Met Ser Tyr Val Met Cys Thr
570 575 580
ggc tca ttc aag tta gag aaa gaa gtg gct gag acc cag cat gga act 1891
Gly Ser Phe Lys Leu Glu Lys Glu Val Ala Glu Thr Gln His Gly Thr
585 590 595
gtt ctg gtg cag gtt aaa tat gaa gga aca gac gca cca tgc aag att 1939
Val Leu Val Gln Val Lys Tyr Glu Gly Thr Asp Ala Pro Cys Lys Ile
600 605 610 615
ccc ttt tcg acc caa gat gag aaa gga gca acc cag aat ggg aga tta 1987
Pro Phe Ser Thr Gln Asp Glu Lys Gly Ala Thr Gln Asn Gly Arg Leu
620 625 630
ata aca gcc aac ccc ata gtc act gac aaa gaa aaa cca gtc aat att 2035
Ile Thr Ala Asn Pro Ile Val Thr Asp Lys Glu Lys Pro Val Asn Ile
635 640 645
gag gca gaa cca ccc ttt ggt gag agc tac atc gtg gta gga gca ggt 2083
Glu Ala Glu Pro Pro Phe Gly Glu Ser Tyr Ile Val Val Gly Ala Gly
650 655 660
gaa aaa gct ttg aaa cta agc tgg ttc aag aaa gga agc agc ata ggg 2131
Glu Lys Ala Leu Lys Leu Ser Trp Phe Lys Lys Gly Ser Ser Ile Gly
665 670 675
aaa atg ttt gaa gca act gcc cga gga gca cga agg atg gcc att ctg 2179
Lys Met Phe Glu Ala Thr Ala Arg Gly Ala Arg Arg Met Ala Ile Leu
680 685 690 695
gga gac acc gca tgg gac ttc ggt tct ata gga gga gtg ttc acg tct 2227
Gly Asp Thr Ala Trp Asp Phe Gly Ser Ile Gly Gly Val Phe Thr Ser
700 705 710
atg gga aaa ctg gta cac cag gtt ttt gga act gca tat gga gtt ttg 2275
Met Gly Lys Leu Val His Gln Val Phe Gly Thr Ala Tyr Gly Val Leu
715 720 725
ttt agc gga gtt tct tgg acc atg aaa ata gga ata ggg att ctg ctg 2323
Phe Ser Gly Val Ser Trp Thr Met Lys Ile Gly Ile Gly Ile Leu Leu
730 735 740
aca tgg cta gga tta aat tca agg aac acg tcc ctt tcg atg atg tgc 2371
Thr Trp Leu Gly Leu Asn Ser Arg Asn Thr Ser Leu Ser Met Met Cys
745 750 755
atc gca gtt ggc atg gtc aca ctg tac cta gga gtc atg gtt cag gca 2419
Ile Ala Val Gly Met Val Thr Leu Tyr Leu Gly Val Met Val Gln Ala
760 765 770 775
gat tcg gga tgt gta atc aac tgg aaa ggc aga gaa ctt aaa tgt gga 2467
Asp Ser Gly Cys Val Ile Asn Trp Lys Gly Arg Glu Leu Lys Cys Gly
780 785 790
agc ggc att ttt gtc act aat gaa gtt cac act tgg aca gag caa tac 2515
Ser Gly Ile Phe Val Thr Asn Glu Val His Thr Trp Thr Glu Gln Tyr
795 800 805
aaa ttc cag gct gac tcc ccc aag aga cta tca gca gcc att ggg aag 2563
Lys Phe Gln Ala Asp Ser Pro Lys Arg Leu Ser Ala Ala Ile Gly Lys
810 815 820
gca tgg gag gag ggt gtg tgt gga atc cga tca gcc act cgt ctc gag 2611
Ala Trp Glu Glu Gly Val Cys Gly Ile Arg Ser Ala Thr Arg Leu Glu
825 830 835
aac atc atg tgg aaa caa ata tca aat gaa ttg aac cac atc cta ctt 2659
Asn Ile Met Trp Lys Gln Ile Ser Asn Glu Leu Asn His Ile Leu Leu
840 845 850 855
gaa aat gac atg aaa ttt aca gtg gtc gtg gga gat gtt agt gga atc 2707
Glu Asn Asp Met Lys Phe Thr Val Val Val Gly Asp Val Ser Gly Ile
860 865 870
ttg gcc caa ggg aaa aaa atg att agg cca caa ccc atg gaa cac aaa 2755
Leu Ala Gln Gly Lys Lys Met Ile Arg Pro Gln Pro Met Glu His Lys
875 880 885
tac tcg tgg aaa agc tgg gga aaa gcc aaa atc ata gga gcg gat gta 2803
Tyr Ser Trp Lys Ser Trp Gly Lys Ala Lys Ile Ile Gly Ala Asp Val
890 895 900
cag aac acc acc ttc atc atc gac ggc cca aac acc cca gaa tgc cct 2851
Gln Asn Thr Thr Phe Ile Ile Asp Gly Pro Asn Thr Pro Glu Cys Pro
905 910 915
gac aat caa aga gca tgg aat att tgg gaa gta gag gac tat gga ttt 2899
Asp Asn Gln Arg Ala Trp Asn Ile Trp Glu Val Glu Asp Tyr Gly Phe
920 925 930 935
ggg att ttc acg aca aac ata tgg ttg aaa ttg cgt gac tcc tac acc 2947
Gly Ile Phe Thr Thr Asn Ile Trp Leu Lys Leu Arg Asp Ser Tyr Thr
940 945 950
caa gta tgt gac cac cgg ctg atg tca gct gcc att aag gac agc aag 2995
Gln Val Cys Asp His Arg Leu Met Ser Ala Ala Ile Lys Asp Ser Lys
955 960 965
gca gtc cat gct gac atg ggg tac tgg ata gaa agt gaa aag aac gag 3043
Ala Val His Ala Asp Met Gly Tyr Trp Ile Glu Ser Glu Lys Asn Glu
970 975 980
aca tgg aag ttg gcg aga gcc tcc ttt ata gaa gtt aag aca tgc atc 3091
Thr Trp Lys Leu Ala Arg Ala Ser Phe Ile Glu Val Lys Thr Cys Ile
985 990 995
tgg cca aaa tcc cac act cta tgg agc aat gga gtt ctg gaa agt 3136
Trp Pro Lys Ser His Thr Leu Trp Ser Asn Gly Val Leu Glu Ser
1000 1005 1010
gaa atg ata att cca aag ata tat gga gga cca ata tct cag cac 3181
Glu Met Ile Ile Pro Lys Ile Tyr Gly Gly Pro Ile Ser Gln His
1015 1020 1025
aac tac aga cca gga tat ttc aca caa aca gca ggg ccg tgg cac 3226
Asn Tyr Arg Pro Gly Tyr Phe Thr Gln Thr Ala Gly Pro Trp His
1030 1035 1040
cta ggc aag ttg gaa cta gat ttc gat ttt tgt gaa ggt acc aca 3271
Leu Gly Lys Leu Glu Leu Asp Phe Asp Phe Cys Glu Gly Thr Thr
1045 1050 1055
gtt gtt gtg gat gaa cat tgt gga aat cga gga cca tct ctc aga 3316
Val Val Val Asp Glu His Cys Gly Asn Arg Gly Pro Ser Leu Arg
1060 1065 1070
acc aca aca gtc aca gga aag ata atc cat gaa tgg tgc tgc aga 3361
Thr Thr Thr Val Thr Gly Lys Ile Ile His Glu Trp Cys Cys Arg
1075 1080 1085
tct tgt acg cta ccc ccc cta cgt ttc aaa ggg gaa gac ggg tgt 3406
Ser Cys Thr Leu Pro Pro Leu Arg Phe Lys Gly Glu Asp Gly Cys
1090 1095 1100
tgg tac ggc atg gaa atc aga cca gtg aag gac aag gaa gag aac 3451
Trp Tyr Gly Met Glu Ile Arg Pro Val Lys Asp Lys Glu Glu Asn
1105 1110 1115
ctg gtc aag tca atg gtc tct gca ggg tca gga gaa gtg gac agc 3496
Leu Val Lys Ser Met Val Ser Ala Gly Ser Gly Glu Val Asp Ser
1120 1125 1130
ttt tca cta gga ctg cta tgc ata tca ata atg att gaa gaa gtg 3541
Phe Ser Leu Gly Leu Leu Cys Ile Ser Ile Met Ile Glu Glu Val
1135 1140 1145
atg aga tcc aga tgg agc aaa aaa atg ctg atg act gga aca ctg 3586
Met Arg Ser Arg Trp Ser Lys Lys Met Leu Met Thr Gly Thr Leu
1150 1155 1160
gct gtg ttc ctc ctt ctt ata atg gga caa ttg aca tgg agt gat 3631
Ala Val Phe Leu Leu Leu Ile Met Gly Gln Leu Thr Trp Ser Asp
1165 1170 1175
ctg atc agg tta tgt att atg gtt gga gcc aac gct tca gac aag 3676
Leu Ile Arg Leu Cys Ile Met Val Gly Ala Asn Ala Ser Asp Lys
1180 1185 1190
atg ggg atg gga aca acg tac cta gct tta atg gcc act ttc aaa 3721
Met Gly Met Gly Thr Thr Tyr Leu Ala Leu Met Ala Thr Phe Lys
1195 1200 1205
atg aga cca atg ttc gcc gtc ggg cta tta ttt cgc aga cta aca 3766
Met Arg Pro Met Phe Ala Val Gly Leu Leu Phe Arg Arg Leu Thr
1210 1215 1220
tct aga gaa gtt ctt ctt ctt aca att ggc ttg agc ctg gtg gca 3811
Ser Arg Glu Val Leu Leu Leu Thr Ile Gly Leu Ser Leu Val Ala
1225 1230 1235
tcc gtg gag cta cca agt tcc cta gag gag ctg ggg gat gga ctt 3856
Ser Val Glu Leu Pro Ser Ser Leu Glu Glu Leu Gly Asp Gly Leu
1240 1245 1250
gca ata ggc atc atg atg ttg aaa tta ttg act gat ttt cag tca 3901
Ala Ile Gly Ile Met Met Leu Lys Leu Leu Thr Asp Phe Gln Ser
1255 1260 1265
cac cag cta tgg gct act ctg cta tcc ttg aca ttt att aaa aca 3946
His Gln Leu Trp Ala Thr Leu Leu Ser Leu Thr Phe Ile Lys Thr
1270 1275 1280
act ttt tca ttg cac tat gca tgg aag aca atg gct atg gta ctg 3991
Thr Phe Ser Leu His Tyr Ala Trp Lys Thr Met Ala Met Val Leu
1285 1290 1295
tca att gta tct ctc ttc cct tta tgc ctg tcc acg acc tct caa 4036
Ser Ile Val Ser Leu Phe Pro Leu Cys Leu Ser Thr Thr Ser Gln
1300 1305 1310
aaa aca aca tgg ctt ccg gtg ctg ttg gga tct ctt gga tgc aaa 4081
Lys Thr Thr Trp Leu Pro Val Leu Leu Gly Ser Leu Gly Cys Lys
1315 1320 1325
cca cta ccc atg ttt ctt ata aca gaa aac aaa atc tgg gga agg 4126
Pro Leu Pro Met Phe Leu Ile Thr Glu Asn Lys Ile Trp Gly Arg
1330 1335 1340
aag agt tgg ccc ctc aat gaa gga att atg gct gtt gga ata gtt 4171
Lys Ser Trp Pro Leu Asn Glu Gly Ile Met Ala Val Gly Ile Val
1345 1350 1355
agt att cta cta agt tca ctt tta aaa aat gat gtg ccg cta gcc 4216
Ser Ile Leu Leu Ser Ser Leu Leu Lys Asn Asp Val Pro Leu Ala
1360 1365 1370
ggc cca tta ata gct gga ggc atg cta ata gca tgt tat gtc ata 4261
Gly Pro Leu Ile Ala Gly Gly Met Leu Ile Ala Cys Tyr Val Ile
1375 1380 1385
tcc gga agc tca gct gat tta tca ctg gag aaa gcg gct gag gtc 4306
Ser Gly Ser Ser Ala Asp Leu Ser Leu Glu Lys Ala Ala Glu Val
1390 1395 1400
tcc tgg gag gaa gaa gca gaa cac tca ggc gcc tca cac aac ata 4351
Ser Trp Glu Glu Glu Ala Glu His Ser Gly Ala Ser His Asn Ile
1405 1410 1415
cta gta gag gtt caa gat gat gga acc atg aag ata aaa gat gaa 4396
Leu Val Glu Val Gln Asp Asp Gly Thr Met Lys Ile Lys Asp Glu
1420 1425 1430
gag aga gat gac acg ctc acc att ctc ctt aaa gca act ctg ctg 4441
Glu Arg Asp Asp Thr Leu Thr Ile Leu Leu Lys Ala Thr Leu Leu
1435 1440 1445
gca gtc tca ggg gtg tac cca atg tca ata cca gcg acc ctt ttt 4486
Ala Val Ser Gly Val Tyr Pro Met Ser Ile Pro Ala Thr Leu Phe
1450 1455 1460
gtg tgg tat ttt tgg cag aaa aag aaa cag aga tca gga gtg cta 4531
Val Trp Tyr Phe Trp Gln Lys Lys Lys Gln Arg Ser Gly Val Leu
1465 1470 1475
tgg gac aca ccc agc ccc cca gaa gtg gaa aga gca gtt ctt gat 4576
Trp Asp Thr Pro Ser Pro Pro Glu Val Glu Arg Ala Val Leu Asp
1480 1485 1490
gat ggc atc tat aga att ttg caa aga gga ctg ttg ggc agg tcc 4621
Asp Gly Ile Tyr Arg Ile Leu Gln Arg Gly Leu Leu Gly Arg Ser
1495 1500 1505
caa gta gga gta gga gtt ttc caa gaa ggc gtg ttc cac aca atg 4666
Gln Val Gly Val Gly Val Phe Gln Glu Gly Val Phe His Thr Met
1510 1515 1520
tgg cac gtc act agg gga gct gtc ctc atg tat caa gga aaa agg 4711
Trp His Val Thr Arg Gly Ala Val Leu Met Tyr Gln Gly Lys Arg
1525 1530 1535
ctg gaa cca agc tgg gcc agt gtc aaa aaa gac ttg atc tca tat 4756
Leu Glu Pro Ser Trp Ala Ser Val Lys Lys Asp Leu Ile Ser Tyr
1540 1545 1550
gga gga ggt tgg agg ttt caa gga tcc tgg aac acg gga gaa gaa 4801
Gly Gly Gly Trp Arg Phe Gln Gly Ser Trp Asn Thr Gly Glu Glu
1555 1560 1565
gta cag gtg att gct gtt gaa ccg gga aaa aac ccc aaa aat gta 4846
Val Gln Val Ile Ala Val Glu Pro Gly Lys Asn Pro Lys Asn Val
1570 1575 1580
caa aca acg ccg ggt acc ttc aag acc cct gaa ggc gaa gtt gga 4891
Gln Thr Thr Pro Gly Thr Phe Lys Thr Pro Glu Gly Glu Val Gly
1585 1590 1595
gcc ata gcc tta gac ttt aaa cct ggc aca tct gga tct ccc atc 4936
Ala Ile Ala Leu Asp Phe Lys Pro Gly Thr Ser Gly Ser Pro Ile
1600 1605 1610
gta aac aga gag gga aaa ata gta ggt ctt tat gga aat gga gtg 4981
Val Asn Arg Glu Gly Lys Ile Val Gly Leu Tyr Gly Asn Gly Val
1615 1620 1625
gtg aca aca agc gga act tac gtt agt gcc ata gct caa gct aag 5026
Val Thr Thr Ser Gly Thr Tyr Val Ser Ala Ile Ala Gln Ala Lys
1630 1635 1640
gca tca caa gaa ggg cct cta cca gag att gag gac gag gtg ttt 5071
Ala Ser Gln Glu Gly Pro Leu Pro Glu Ile Glu Asp Glu Val Phe
1645 1650 1655
agg aaa aga aac tta aca ata atg gac cta cat cca gga tcg gga 5116
Arg Lys Arg Asn Leu Thr Ile Met Asp Leu His Pro Gly Ser Gly
1660 1665 1670
aaa aca aga aga tac ctt cca gcc ata gtc cgt gag gcc ata aaa 5161
Lys Thr Arg Arg Tyr Leu Pro Ala Ile Val Arg Glu Ala Ile Lys
1675 1680 1685
agg aag ctg cgc acg cta atc cta gct ccc aca aga gtt gtc gct 5206
Arg Lys Leu Arg Thr Leu Ile Leu Ala Pro Thr Arg Val Val Ala
1690 1695 1700
tct gaa atg gca gag gca ctc aag gga gtg cca ata agg tat cag 5251
Ser Glu Met Ala Glu Ala Leu Lys Gly Val Pro Ile Arg Tyr Gln
1705 1710 1715
aca aca gca gtg aag agt gaa cac aca gga aag gag ata gtt gac 5296
Thr Thr Ala Val Lys Ser Glu His Thr Gly Lys Glu Ile Val Asp
1720 1725 1730
ctt atg tgc cac gcc act ttc acc atg cgc ctc ctg tct ccc gtg 5341
Leu Met Cys His Ala Thr Phe Thr Met Arg Leu Leu Ser Pro Val
1735 1740 1745
aga gtt ccc aat tat aac atg att atc atg gat gaa gca cac ttc 5386
Arg Val Pro Asn Tyr Asn Met Ile Ile Met Asp Glu Ala His Phe
1750 1755 1760
acc gat cca gcc agc ata gca gcc aga ggg tac atc tca acc cga 5431
Thr Asp Pro Ala Ser Ile Ala Ala Arg Gly Tyr Ile Ser Thr Arg
1765 1770 1775
gtg ggt atg ggt gaa gca gct gcg atc ttt atg aca gcc act ccc 5476
Val Gly Met Gly Glu Ala Ala Ala Ile Phe Met Thr Ala Thr Pro
1780 1785 1790
cca gga tcg gtg gag gcc ttt cca cag agc aat gca att atc caa 5521
Pro Gly Ser Val Glu Ala Phe Pro Gln Ser Asn Ala Ile Ile Gln
1795 1800 1805
gat gag gaa aga gac att cct gag aga tca tgg aac tca ggc tat 5566
Asp Glu Glu Arg Asp Ile Pro Glu Arg Ser Trp Asn Ser Gly Tyr
1810 1815 1820
gac tgg atc act gat ttt cca ggt aaa aca gtc tgg ttt gtt cca 5611
Asp Trp Ile Thr Asp Phe Pro Gly Lys Thr Val Trp Phe Val Pro
1825 1830 1835
agc atc aaa tca gga aat gac att gcc aac tgt tta aga aaa aac 5656
Ser Ile Lys Ser Gly Asn Asp Ile Ala Asn Cys Leu Arg Lys Asn
1840 1845 1850
ggg aaa cgg gtg atc caa ttg agc aga aaa acc ttt gac act gag 5701
Gly Lys Arg Val Ile Gln Leu Ser Arg Lys Thr Phe Asp Thr Glu
1855 1860 1865
tac cag aaa aca aaa aac aac gac tgg gac tat gtc gtc aca aca 5746
Tyr Gln Lys Thr Lys Asn Asn Asp Trp Asp Tyr Val Val Thr Thr
1870 1875 1880
gac att tcc gaa atg gga gca aat ttc cgg gcc gac agg gta ata 5791
Asp Ile Ser Glu Met Gly Ala Asn Phe Arg Ala Asp Arg Val Ile
1885 1890 1895
gac cca agg cgg tgt ctg aaa ccg gta ata cta aaa gat ggt cca 5836
Asp Pro Arg Arg Cys Leu Lys Pro Val Ile Leu Lys Asp Gly Pro
1900 1905 1910
gag cgc gtc att cta gcc gga ccg atg cca gtg act gtg gcc agt 5881
Glu Arg Val Ile Leu Ala Gly Pro Met Pro Val Thr Val Ala Ser
1915 1920 1925
gcc gcc cag agg aga gga aga att gga agg aac caa aac aag gaa 5926
Ala Ala Gln Arg Arg Gly Arg Ile Gly Arg Asn Gln Asn Lys Glu
1930 1935 1940
ggt gat cag tat att tac atg gga cag cct tta aac aat gat gag 5971
Gly Asp Gln Tyr Ile Tyr Met Gly Gln Pro Leu Asn Asn Asp Glu
1945 1950 1955
gac cac gct cat tgg aca gaa gca aag atg ctc ctt gac aat ata 6016
Asp His Ala His Trp Thr Glu Ala Lys Met Leu Leu Asp Asn Ile
1960 1965 1970
aac aca cca gaa ggg att atc cca gcc ctc tat gag ccg gag aga 6061
Asn Thr Pro Glu Gly Ile Ile Pro Ala Leu Tyr Glu Pro Glu Arg
1975 1980 1985
gaa aag agt gca gct ata gac ggg gaa tac aga ctg cgg ggt gaa 6106
Glu Lys Ser Ala Ala Ile Asp Gly Glu Tyr Arg Leu Arg Gly Glu
1990 1995 2000
gca agg aaa acg ttc gtg gag ctc atg aga aga ggg gat cta cca 6151
Ala Arg Lys Thr Phe Val Glu Leu Met Arg Arg Gly Asp Leu Pro
2005 2010 2015
gtc tgg cta tcc tac aaa gtt gcc tca gaa ggc ttc cag tac tcc 6196
Val Trp Leu Ser Tyr Lys Val Ala Ser Glu Gly Phe Gln Tyr Ser
2020 2025 2030
gac aga agg tgg tgc ttc gat ggg gaa agg aac aac cag gtg ttg 6241
Asp Arg Arg Trp Cys Phe Asp Gly Glu Arg Asn Asn Gln Val Leu
2035 2040 2045
gag gag aac atg gac gtg gag atc tgg aca aaa gaa gga gaa aga 6286
Glu Glu Asn Met Asp Val Glu Ile Trp Thr Lys Glu Gly Glu Arg
2050 2055 2060
aag aaa cta cga cct cgc tgg ttg gac gcc aga aca tac tct gac 6331
Lys Lys Leu Arg Pro Arg Trp Leu Asp Ala Arg Thr Tyr Ser Asp
2065 2070 2075
cca ctg gct ctg cgc gag ttt aaa gag ttt gca gca gga aga aga 6376
Pro Leu Ala Leu Arg Glu Phe Lys Glu Phe Ala Ala Gly Arg Arg
2080 2085 2090
agc gtc tca ggt gac cta ata tta gaa ata ggg aaa ctt cca caa 6421
Ser Val Ser Gly Asp Leu Ile Leu Glu Ile Gly Lys Leu Pro Gln
2095 2100 2105
cat ttg acg caa agg gcc cag aat gct ttg gac aac ttg gtc atg 6466
His Leu Thr Gln Arg Ala Gln Asn Ala Leu Asp Asn Leu Val Met
2110 2115 2120
ttg cac aat tcc gaa caa gga gga aaa gcc tat aga cat gct atg 6511
Leu His Asn Ser Glu Gln Gly Gly Lys Ala Tyr Arg His Ala Met
2125 2130 2135
gaa gaa ctg cca gac aca ata gaa acg ttg atg ctc cta gcc ttg 6556
Glu Glu Leu Pro Asp Thr Ile Glu Thr Leu Met Leu Leu Ala Leu
2140 2145 2150
ata gct gtg ttg act ggt gga gtg acg ctg ttc ttc cta tca gga 6601
Ile Ala Val Leu Thr Gly Gly Val Thr Leu Phe Phe Leu Ser Gly
2155 2160 2165
aga ggt cta gga aaa aca tct atc ggc tta ctc tgc gtg atg gcc 6646
Arg Gly Leu Gly Lys Thr Ser Ile Gly Leu Leu Cys Val Met Ala
2170 2175 2180
tca agc gca ctg tta tgg atg gcc agt gtg gag ccc cat tgg ata 6691
Ser Ser Ala Leu Leu Trp Met Ala Ser Val Glu Pro His Trp Ile
2185 2190 2195
gcg gcc tcc atc ata ctg gag ttc ttt ctg atg gta ctg ctt att 6736
Ala Ala Ser Ile Ile Leu Glu Phe Phe Leu Met Val Leu Leu Ile
2200 2205 2210
cca gag cca gac aga cag cgc act cca cag gac aac cag cta gca 6781
Pro Glu Pro Asp Arg Gln Arg Thr Pro Gln Asp Asn Gln Leu Ala
2215 2220 2225
tat gtg gtg ata ggt ctg tta ttc atg ata ttg aca gtg gca gcc 6826
Tyr Val Val Ile Gly Leu Leu Phe Met Ile Leu Thr Val Ala Ala
2230 2235 2240
aat gag atg gga tta ttg gaa acc aca aag aaa gac ctg ggg att 6871
Asn Glu Met Gly Leu Leu Glu Thr Thr Lys Lys Asp Leu Gly Ile
2245 2250 2255
ggc cat gta gct gct gaa aac cac cac cat gct aca atg ctg gac 6916
Gly His Val Ala Ala Glu Asn His His His Ala Thr Met Leu Asp
2260 2265 2270
gta gac cta cat cca gct tca gcc tgg acc ctc tat gca gtg gcc 6961
Val Asp Leu His Pro Ala Ser Ala Trp Thr Leu Tyr Ala Val Ala
2275 2280 2285
aca aca atc atc act cct atg atg aga cac aca att gaa aac aca 7006
Thr Thr Ile Ile Thr Pro Met Met Arg His Thr Ile Glu Asn Thr
2290 2295 2300
acg gca aat att tcc ctg aca gcc atc gca aac caa gca gct ata 7051
Thr Ala Asn Ile Ser Leu Thr Ala Ile Ala Asn Gln Ala Ala Ile
2305 2310 2315
ttg atg gga ctt gac aag gga tgg cca ata tcg aag atg gac ata 7096
Leu Met Gly Leu Asp Lys Gly Trp Pro Ile Ser Lys Met Asp Ile
2320 2325 2330
gga gtt cca ctt ctc gcc ttg ggg tgc tat tcc caa gtg aat ccg 7141
Gly Val Pro Leu Leu Ala Leu Gly Cys Tyr Ser Gln Val Asn Pro
2335 2340 2345
ctg aca ctg ata gcg gca gta ttg atg cta gta gct cat tac gcc 7186
Leu Thr Leu Ile Ala Ala Val Leu Met Leu Val Ala His Tyr Ala
2350 2355 2360
ata att gga cct gga ctg caa gca aaa gct act aga gaa gct caa 7231
Ile Ile Gly Pro Gly Leu Gln Ala Lys Ala Thr Arg Glu Ala Gln
2365 2370 2375
aaa aga aca gcg gct gga ata atg aaa aat cca act gtc gac ggg 7276
Lys Arg Thr Ala Ala Gly Ile Met Lys Asn Pro Thr Val Asp Gly
2380 2385 2390
att gtt gca ata gac tta gat ccc gtg gtt tac gat gca aaa ttt 7321
Ile Val Ala Ile Asp Leu Asp Pro Val Val Tyr Asp Ala Lys Phe
2395 2400 2405
gaa aaa caa cta ggc caa ata atg ttg ttg ata ctt tgc aca tca 7366
Glu Lys Gln Leu Gly Gln Ile Met Leu Leu Ile Leu Cys Thr Ser
2410 2415 2420
cag att ctt ttg atg cgg act aca tgg gcc ttg tgt gaa tcc atc 7411
Gln Ile Leu Leu Met Arg Thr Thr Trp Ala Leu Cys Glu Ser Ile
2425 2430 2435
aca ttg gct act gga cct ctg acc act ctt tgg gag gga tct cca 7456
Thr Leu Ala Thr Gly Pro Leu Thr Thr Leu Trp Glu Gly Ser Pro
2440 2445 2450
gga aaa ttc tgg aac acc aca ata gcg gta tcc atg gca aac att 7501
Gly Lys Phe Trp Asn Thr Thr Ile Ala Val Ser Met Ala Asn Ile
2455 2460 2465
ttc agg ggg agt tat cta gca gga gca ggt ctg gcc ttc tca tta 7546
Phe Arg Gly Ser Tyr Leu Ala Gly Ala Gly Leu Ala Phe Ser Leu
2470 2475 2480
atg aaa tct cta gga gga ggt agg aga ggc acg gga gcc caa ggg 7591
Met Lys Ser Leu Gly Gly Gly Arg Arg Gly Thr Gly Ala Gln Gly
2485 2490 2495
gaa aca ctg gga gaa aaa tgg aaa aga caa cta aac caa ctg agc 7636
Glu Thr Leu Gly Glu Lys Trp Lys Arg Gln Leu Asn Gln Leu Ser
2500 2505 2510
aag tca gaa ttc aat act tac aag agg agt ggg att atg gag gtg 7681
Lys Ser Glu Phe Asn Thr Tyr Lys Arg Ser Gly Ile Met Glu Val
2515 2520 2525
gat aga tcc gaa gcc aaa gag gga ctg aaa aga gga gaa aca acc 7726
Asp Arg Ser Glu Ala Lys Glu Gly Leu Lys Arg Gly Glu Thr Thr
2530 2535 2540
aaa cac gca gta tcg aga gga acg gcc aaa ctg agg tgg ttc gtg 7771
Lys His Ala Val Ser Arg Gly Thr Ala Lys Leu Arg Trp Phe Val
2545 2550 2555
gag agg aac ctt gtg aaa cca gaa ggg aaa gtc ata gac ctc ggt 7816
Glu Arg Asn Leu Val Lys Pro Glu Gly Lys Val Ile Asp Leu Gly
2560 2565 2570
tgt gga aga ggt ggc tgg tca tat tat tgc gct ggg ctg aag aaa 7861
Cys Gly Arg Gly Gly Trp Ser Tyr Tyr Cys Ala Gly Leu Lys Lys
2575 2580 2585
gtc aca gaa gtg aaa gga tac aca aaa gga gga cct gga cat gag 7906
Val Thr Glu Val Lys Gly Tyr Thr Lys Gly Gly Pro Gly His Glu
2590 2595 2600
gaa cca atc cca atg gcg acc tat gga tgg aac cta gta aag ctg 7951
Glu Pro Ile Pro Met Ala Thr Tyr Gly Trp Asn Leu Val Lys Leu
2605 2610 2615
cac tcc gga aaa gat gta ttt ttt ata cca cct gag aaa tgt gac 7996
His Ser Gly Lys Asp Val Phe Phe Ile Pro Pro Glu Lys Cys Asp
2620 2625 2630
acc ctt ttg tgt gat att ggt gag tcc tct ccg aac cca act ata 8041
Thr Leu Leu Cys Asp Ile Gly Glu Ser Ser Pro Asn Pro Thr Ile
2635 2640 2645
gag gaa gga aga acg tta cgt gtt ctg aaa atg gtg gaa cca tgg 8086
Glu Glu Gly Arg Thr Leu Arg Val Leu Lys Met Val Glu Pro Trp
2650 2655 2660
ctc aga gga aac caa ttt tgc ata aaa att cta aat ccc tat atg 8131
Leu Arg Gly Asn Gln Phe Cys Ile Lys Ile Leu Asn Pro Tyr Met
2665 2670 2675
ccg agc gtg gta gaa act ctg gaa caa atg caa aga aaa cat gga 8176
Pro Ser Val Val Glu Thr Leu Glu Gln Met Gln Arg Lys His Gly
2680 2685 2690
gga atg cta gtg cga aac cca ctc tca aga aat tcc acc cat gaa 8221
Gly Met Leu Val Arg Asn Pro Leu Ser Arg Asn Ser Thr His Glu
2695 2700 2705
atg tac tgg gtt tca tgt gga aca gga aac att gtg tca gca gta 8266
Met Tyr Trp Val Ser Cys Gly Thr Gly Asn Ile Val Ser Ala Val
2710 2715 2720
aac atg aca tct aga atg ttg cta aat cgg ttc aca atg gct cac 8311
Asn Met Thr Ser Arg Met Leu Leu Asn Arg Phe Thr Met Ala His
2725 2730 2735
agg aag cca aca tat gaa aga gac gtg gac tta ggc gct gga aca 8356
Arg Lys Pro Thr Tyr Glu Arg Asp Val Asp Leu Gly Ala Gly Thr
2740 2745 2750
aga cat gtg gca gta gaa cca gag gta gcc aac cta gat atc att 8401
Arg His Val Ala Val Glu Pro Glu Val Ala Asn Leu Asp Ile Ile
2755 2760 2765
ggc cag agg ata gag aat ata aaa aat gaa cat aag tca aca tgg 8446
Gly Gln Arg Ile Glu Asn Ile Lys Asn Glu His Lys Ser Thr Trp
2770 2775 2780
cat tat gat gag gac aat cca tac aaa aca tgg gcc tat cat gga 8491
His Tyr Asp Glu Asp Asn Pro Tyr Lys Thr Trp Ala Tyr His Gly
2785 2790 2795
tca tat gag gtt aag cca tca gga tcg gcc tca tcc atg gtc aat 8536
Ser Tyr Glu Val Lys Pro Ser Gly Ser Ala Ser Ser Met Val Asn
2800 2805 2810
ggc gtg gtg aga ttg ctc acc aaa cca tgg gat gtt atc ccc atg 8581
Gly Val Val Arg Leu Leu Thr Lys Pro Trp Asp Val Ile Pro Met
2815 2820 2825
gtc aca caa ata gcc atg act gat acc aca ccc ttt gga caa cag 8626
Val Thr Gln Ile Ala Met Thr Asp Thr Thr Pro Phe Gly Gln Gln
2830 2835 2840
agg gtg ttt aaa gag aaa gtt gac acg cgc aca cca aaa gca aaa 8671
Arg Val Phe Lys Glu Lys Val Asp Thr Arg Thr Pro Lys Ala Lys
2845 2850 2855
cgt ggc aca gca caa att atg gaa gtg aca gcc agg tgg tta tgg 8716
Arg Gly Thr Ala Gln Ile Met Glu Val Thr Ala Arg Trp Leu Trp
2860 2865 2870
ggt ttc ctt tct aga aac aaa aaa ccc aga att tgc aca aga gag 8761
Gly Phe Leu Ser Arg Asn Lys Lys Pro Arg Ile Cys Thr Arg Glu
2875 2880 2885
gag ttt aca aga aaa gtt agg tca aac gca gct att gga gca gtg 8806
Glu Phe Thr Arg Lys Val Arg Ser Asn Ala Ala Ile Gly Ala Val
2890 2895 2900
ttc gtt gat gaa aat caa tgg aac tcg gca aaa gaa gca gtg gaa 8851
Phe Val Asp Glu Asn Gln Trp Asn Ser Ala Lys Glu Ala Val Glu
2905 2910 2915
gac gaa cgg ttc tgg gaa ctt gtc cac aga gag agg gag ctt cat 8896
Asp Glu Arg Phe Trp Glu Leu Val His Arg Glu Arg Glu Leu His
2920 2925 2930
aaa cag ggg aaa tgt gcc acg tgt gtc tac aat atg atg ggg aag 8941
Lys Gln Gly Lys Cys Ala Thr Cys Val Tyr Asn Met Met Gly Lys
2935 2940 2945
aga gag aaa aaa tta gga gag ttc gga aag gca aaa gga agt cgt 8986
Arg Glu Lys Lys Leu Gly Glu Phe Gly Lys Ala Lys Gly Ser Arg
2950 2955 2960
gca ata tgg tac atg tgg ttg gga gca cgc ttc cta gag ttt gaa 9031
Ala Ile Trp Tyr Met Trp Leu Gly Ala Arg Phe Leu Glu Phe Glu
2965 2970 2975
gcc ctt ggt ttc atg aat gaa gat cac tgg ttc agt aga gag aat 9076
Ala Leu Gly Phe Met Asn Glu Asp His Trp Phe Ser Arg Glu Asn
2980 2985 2990
tca ctc agt gga gtg gaa gga gaa gga ctc cac aaa ctt gga tac 9121
Ser Leu Ser Gly Val Glu Gly Glu Gly Leu His Lys Leu Gly Tyr
2995 3000 3005
ata ctc aga gac ata tca agg att cca ggg ggg aac atg tat gca 9166
Ile Leu Arg Asp Ile Ser Arg Ile Pro Gly Gly Asn Met Tyr Ala
3010 3015 3020
gat gac aca gcc gga tgg gac aca aga ata aca gag gat gat ctc 9211
Asp Asp Thr Ala Gly Trp Asp Thr Arg Ile Thr Glu Asp Asp Leu
3025 3030 3035
cag aat gag gct aaa atc act gac atc atg gag ccc gaa cat gcc 9256
Gln Asn Glu Ala Lys Ile Thr Asp Ile Met Glu Pro Glu His Ala
3040 3045 3050
ctg ctg gct acg tca atc ttt aag ctg acc tac caa aat aag gtg 9301
Leu Leu Ala Thr Ser Ile Phe Lys Leu Thr Tyr Gln Asn Lys Val
3055 3060 3065
gta agg gtg cag aga cca gca aaa aat gga acc gtg atg gat gtt 9346
Val Arg Val Gln Arg Pro Ala Lys Asn Gly Thr Val Met Asp Val
3070 3075 3080
ata tcc aga cgt gac cag aga ggc agt gga cag gtt gga act tat 9391
Ile Ser Arg Arg Asp Gln Arg Gly Ser Gly Gln Val Gly Thr Tyr
3085 3090 3095
ggc tta aac act ttc acc aac atg gag gcc caa ctg ata aga caa 9436
Gly Leu Asn Thr Phe Thr Asn Met Glu Ala Gln Leu Ile Arg Gln
3100 3105 3110
atg gag tcc gag gga atc ttt tta ccc agc gaa ttg gaa acc cca 9481
Met Glu Ser Glu Gly Ile Phe Leu Pro Ser Glu Leu Glu Thr Pro
3115 3120 3125
aat cta gcc gga aga gtt ctc gac tgg ttg gaa aaa tat ggt gtc 9526
Asn Leu Ala Gly Arg Val Leu Asp Trp Leu Glu Lys Tyr Gly Val
3130 3135 3140
gaa agg ctg aaa aga atg gca atc agc gga gat gac tgt gtg gtg 9571
Glu Arg Leu Lys Arg Met Ala Ile Ser Gly Asp Asp Cys Val Val
3145 3150 3155
aaa cca att gat gac agg ttc gca aca gcc tta aca gct ttg aat 9616
Lys Pro Ile Asp Asp Arg Phe Ala Thr Ala Leu Thr Ala Leu Asn
3160 3165 3170
gac atg gga aaa gta aga aaa gac ata cca caa tgg gaa cct tca 9661
Asp Met Gly Lys Val Arg Lys Asp Ile Pro Gln Trp Glu Pro Ser
3175 3180 3185
aaa gga tgg aat gat tgg caa caa gtg cct ttc tgt tca cac cac 9706
Lys Gly Trp Asn Asp Trp Gln Gln Val Pro Phe Cys Ser His His
3190 3195 3200
ttc cac cag cta att atg aag gat ggg agg gag ata gtg gtg cca 9751
Phe His Gln Leu Ile Met Lys Asp Gly Arg Glu Ile Val Val Pro
3205 3210 3215
tgc cgc aac caa gat gaa ctt gtg ggg agg gcc aga gta tca caa 9796
Cys Arg Asn Gln Asp Glu Leu Val Gly Arg Ala Arg Val Ser Gln
3220 3225 3230
ggc gcc gga tgg agc ctg aga gaa acc gca tgc cta ggc aag tca 9841
Gly Ala Gly Trp Ser Leu Arg Glu Thr Ala Cys Leu Gly Lys Ser
3235 3240 3245
tat gca caa atg tgg cag ctg atg tat ttc cac agg aga gac ctg 9886
Tyr Ala Gln Met Trp Gln Leu Met Tyr Phe His Arg Arg Asp Leu
3250 3255 3260
aga ctg gcg gct aac gct att tgt tca gcc gtt cca gtt gat tgg 9931
Arg Leu Ala Ala Asn Ala Ile Cys Ser Ala Val Pro Val Asp Trp
3265 3270 3275
gtc cca acc agc cgc acc acc tgg tcg atc cat gcc cat cac caa 9976
Val Pro Thr Ser Arg Thr Thr Trp Ser Ile His Ala His His Gln
3280 3285 3290
tgg atg aca aca gaa gac atg tta tca gta tgg aat agg gtc tgg 10021
Trp Met Thr Thr Glu Asp Met Leu Ser Val Trp Asn Arg Val Trp
3295 3300 3305
ata gag gaa aac cca tgg atg gag gat aag act cat gtg tcc agt 10066
Ile Glu Glu Asn Pro Trp Met Glu Asp Lys Thr His Val Ser Ser
3310 3315 3320
tgg gaa gaa gtt cca tac cta gga aag agg gaa gat cag tgg tgt 10111
Trp Glu Glu Val Pro Tyr Leu Gly Lys Arg Glu Asp Gln Trp Cys
3325 3330 3335
gga tcc ctg ata ggc tta aca gca agg gcc acc tgg gcc act aat 10156
Gly Ser Leu Ile Gly Leu Thr Ala Arg Ala Thr Trp Ala Thr Asn
3340 3345 3350
ata caa gtg gcc ata aac caa gtg aga agg ctc att ggg aat gag 10201
Ile Gln Val Ala Ile Asn Gln Val Arg Arg Leu Ile Gly Asn Glu
3355 3360 3365
aat tat cta gat tac atg aca tca atg aag aga ttc aag aat gag 10246
Asn Tyr Leu Asp Tyr Met Thr Ser Met Lys Arg Phe Lys Asn Glu
3370 3375 3380
agt gat ccc gaa ggg gca ctc tgg taa gtcaacacat tcacaaaata 10293
Ser Asp Pro Glu Gly Ala Leu Trp
3385 3390
aaggaaaata aaaaatcaaa tgaggcaaga agtcaggcca gattaagcca tagtacggta10353
agagctatgc tgcctgtgag ccccgtccaa ggacgtaaaa tgaagtcagg ccgaaagcca10413
cggtttgagc aagccgtgct gcctgtggct ccatcgtggg gatgtaaaaa cccgggaggc10473
tgcaacccat ggaagctgta cgcatggggt agcagactag tggttagagg agacccctcc10533
caagacacaa cgcagcagcg gggcccaaca ccaggggaag ctgtaccctg gtggtaagga10593
ctagaggtta gaggagaccc cccgcgtaac aataaacagc atattgacgc tgggagagac10653
cagagatcct gctgtctcta cagcatcatt ccaggcacag aacgccagaa aatggaatgg10713
tgctgttgaa tcaacaggtt ct 10735
<210> 4
<211> 3392
<212> PRT
<213> 1型登革病毒
<400> 4
Met Ile Asn Gln Arg Lys Lys Thr Gly Arg Pro Ser Phe Asn Met Leu
1 5 10 15
Lys Arg Ala Arg Asn Arg Val Ser Thr Val Ser Gln Leu Ala Lys Arg
20 25 30
Phe Ser Lys Gly Leu Leu Ser Gly Gln Gly Pro Met Lys Leu Val Met
35 40 45
Ala Phe Ile Ala Phe Leu Arg Phe Leu Ala Ile Pro Pro Thr Ala Gly
50 55 60
Ile Leu Ala Arg Trp Gly Ser Phe Lys Lys Asn Gly Ala Ile Lys Val
65 70 75 80
Leu Arg Gly Phe Lys Arg Glu Ile Ser Asn Met Leu Asn Ile Met Asn
85 90 95
Arg Arg Lys Arg Ser Val Thr Met Leu Leu Met Leu Leu Pro Thr Ala
100 105 110
Leu Ala Phe His Leu Thr Thr Arg Gly Gly Glu Pro His Met Ile Val
115 120 125
Ser Lys Gln Glu Arg Gly Lys Ser Leu Leu Phe Lys Thr Ser Ala Gly
130 135 140
Val Asn Met Cys Thr Leu Ile Ala Met Asp Leu Gly Glu Leu Cys Glu
145 150 155 160
Asp Thr Met Thr Tyr Lys Cys Pro Arg Ile Thr Glu Ala Glu Pro Asp
165 170 175
Asp Val Asp Cys Trp Cys Asn Ala Thr Asp Thr Trp Val Thr Tyr Gly
180 185 190
Thr Cys Ser Gln Thr Gly Glu His Arg Arg Asp Lys Arg Ser Val Ala
195 200 205
Leu Ala Pro His Val Gly Leu Gly Leu Glu Thr Arg Ala Glu Thr Trp
210 215 220
Met Ser Ser Glu Gly Ala Trp Lys Gln Ile Gln Lys Val Glu Thr Trp
225 230 235 240
Ala Leu Arg His Pro Gly Phe Thr Val Ile Ala Leu Phe Leu Ala His
245 250 255
Ala Ile Gly Thr Ser Ile Thr Gln Lys Gly Ile Ile Phe Ile Leu Leu
260 265 270
Met Leu Val Thr Pro Ser Met Ala Met Arg Cys Val Gly Ile Gly Asn
275 280 285
Arg Asp Phe Val Glu Gly Leu Ser Gly Ala Thr Trp Val Asp Val Val
290 295 300
Leu Glu His Gly Ser Cys Val Thr Thr Met Ala Lys Asn Lys Pro Thr
305 310 315 320
Leu Asp Ile Glu Leu Leu Lys Thr Glu Val Thr Asn Pro Ala Val Leu
325 330 335
Arg Lys Leu Cys Ile Glu Ala Lys Ile Ser Asn Thr Thr Thr Asp Ser
340 345 350
Arg Cys Pro Thr Gln Gly Glu Ala Thr Leu Val Glu Glu Gln Asp Ala
355 360 365
Asn Phe Val Cys Arg Arg Thr Phe Val Asp Arg Gly Trp Gly Asn Gly
370 375 380
Cys Gly Leu Phe Gly Lys Gly Ser Leu Ile Thr Cys Ala Lys Phe Lys
385 390 395 400
Cys Val Thr Lys Leu Glu Gly Lys Ile Val Gln Tyr Glu Asn Leu Lys
405 410 415
Tyr Ser Val Ile Val Thr Val His Thr Gly Asp Gln His Gln Val Gly
420 425 430
Asn Glu Thr Thr Glu His Gly Thr Thr Ala Thr Ile Thr Pro Gln Ala
435 440 445
Pro Thr Ser Glu Ile Gln Leu Thr Asp Tyr Gly Thr Leu Thr Leu Asp
450 455 460
Cys Ser Pro Arg Thr Gly Leu Asp Phe Asn Glu Met Val Leu Leu Thr
465 470 475 480
Met Lys Glu Arg Ser Trp Leu Val His Lys Gln Trp Phe Leu Asp Leu
485 490 495
Pro Leu Pro Trp Thr Ser Gly Ala Ser Thr Ser Gln Glu Thr Trp Asn
500 505 510
Arg Gln Asp Leu Leu Val Thr Phe Lys Thr Ala His Ala Lys Lys Gln
515 520 525
Glu Val Val Val Leu Gly Ser Gln Glu Gly Ala Met His Thr Ala Leu
530 535 540
Thr Gly Ala Thr Glu Ile Gln Thr Ser Gly Thr Thr Thr Ile Phe Ala
545 550 555 560
Gly His Leu Lys Cys Arg Leu Lys Met Asp Lys Leu Thr Leu Lys Gly
565 570 575
Met Ser Tyr Val Met Cys Thr Gly Ser Phe Lys Leu Glu Lys Glu Val
580 585 590
Ala Glu Thr Gln His Gly Thr Val Leu Val Gln Val Lys Tyr Glu Gly
595 600 605
Thr Asp Ala Pro Cys Lys Ile Pro Phe Ser Thr Gln Asp Glu Lys Gly
610 615 620
Ala Thr Gln Asn Gly Arg Leu Ile Thr Ala Asn Pro Ile Val Thr Asp
625 630 635 640
Lys Glu Lys Pro Val Asn Ile Glu Ala Glu Pro Pro Phe Gly Glu Ser
645 650 655
Tyr Ile Val Val Gly Ala Gly Glu Lys Ala Leu Lys Leu Ser Trp Phe
660 665 670
Lys Lys Gly Ser Ser Ile Gly Lys Met Phe Glu Ala Thr Ala Arg Gly
675 680 685
Ala Arg Arg Met Ala Ile Leu Gly Asp Thr Ala Trp Asp Phe Gly Ser
690 695 700
Ile Gly Gly Val Phe Thr Ser Met Gly Lys Leu Val His Gln Val Phe
705 710 715 720
Gly Thr Ala Tyr Gly Val Leu Phe Ser Gly Val Ser Trp Thr Met Lys
725 730 735
Ile Gly Ile Gly Ile Leu Leu Thr Trp Leu Gly Leu Asn Ser Arg Asn
740 745 750
Thr Ser Leu Ser Met Met Cys Ile Ala Val Gly Met Val Thr Leu Tyr
755 760 765
Leu Gly Val Met Val Gln Ala Asp Ser Gly Cys Val Ile Asn Trp Lys
770 775 780
Gly Arg Glu Leu Lys Cys Gly Ser Gly Ile Phe Val Thr Asn Glu Val
785 790 795 800
His Thr Trp Thr Glu Gln Tyr Lys Phe Gln Ala Asp Ser Pro Lys Arg
805 810 815
Leu Ser Ala Ala Ile Gly Lys Ala Trp Glu Glu Gly Val Cys Gly Ile
820 825 830
Arg Ser Ala Thr Arg Leu Glu Asn Ile Met Trp Lys Gln Ile Ser Asn
835 840 845
Glu Leu Asn His Ile Leu Leu Glu Asn Asp Met Lys Phe Thr Val Val
850 855 860
Val Gly Asp Val Ser Gly Ile Leu Ala Gln Gly Lys Lys Met Ile Arg
865 870 875 880
Pro Gln Pro Met Glu His Lys Tyr Ser Trp Lys Ser Trp Gly Lys Ala
885 890 895
Lys Ile Ile Gly Ala Asp Val Gln Asn Thr Thr Phe Ile Ile Asp Gly
900 905 910
Pro Asn Thr Pro Glu Cys Pro Asp Asn Gln Arg Ala Trp Asn Ile Trp
915 920 925
Glu Val Glu Asp Tyr Gly Phe Gly Ile Phe Thr Thr Asn Ile Trp Leu
930 935 940
Lys Leu Arg Asp Ser Tyr Thr Gln Val Cys Asp His Arg Leu Met Ser
945 950 955 960
Ala Ala Ile Lys Asp Ser Lys Ala Val His Ala Asp Met Gly Tyr Trp
965 970 975
Ile Glu Ser Glu Lys Asn Glu Thr Trp Lys Leu Ala Arg Ala Ser Phe
980 985 990
Ile Glu Val Lys Thr Cys Ile Trp Pro Lys Ser His Thr Leu Trp Ser
995 1000 1005
Asn Gly Val Leu Glu Ser Glu Met Ile Ile Pro Lys Ile Tyr Gly
1010 1015 1020
Gly Pro Ile Ser Gln His Asn Tyr Arg Pro Gly Tyr Phe Thr Gln
1025 1030 1035
Thr Ala Gly Pro Trp His Leu Gly Lys Leu Glu Leu Asp Phe Asp
1040 1045 1050
Phe Cys Glu Gly Thr Thr Val Val Val Asp Glu His Cys Gly Asn
1055 1060 1065
Arg Gly Pro Ser Leu Arg Thr Thr Thr Val Thr Gly Lys Ile Ile
1070 1075 1080
His Glu Trp Cys Cys Arg Ser Cys Thr Leu Pro Pro Leu Arg Phe
1085 1090 1095
Lys Gly Glu Asp Gly Cys Trp Tyr Gly Met Glu Ile Arg Pro Val
1100 1105 1110
Lys Asp Lys Glu Glu Asn Leu Val Lys Ser Met Val Ser Ala Gly
1115 1120 1125
Ser Gly Glu Val Asp Ser Phe Ser Leu Gly Leu Leu Cys Ile Ser
1130 1135 1140
Ile Met Ile Glu Glu Val Met Arg Ser Arg Trp Ser Lys Lys Met
1145 1150 1155
Leu Met Thr Gly Thr Leu Ala Val Phe Leu Leu Leu Ile Met Gly
1160 1165 1170
Gln Leu Thr Trp Ser Asp Leu Ile Arg Leu Cys Ile Met Val Gly
1175 1180 1185
Ala Asn Ala Ser Asp Lys Met Gly Met Gly Thr Thr Tyr Leu Ala
1190 1195 1200
Leu Met Ala Thr Phe Lys Met Arg Pro Met Phe Ala Val Gly Leu
1205 1210 1215
Leu Phe Arg Arg Leu Thr Ser Arg Glu Val Leu Leu Leu Thr Ile
1220 1225 1230
Gly Leu Ser Leu Val Ala Ser Val Glu Leu Pro Ser Ser Leu Glu
1235 1240 1245
Glu Leu Gly Asp Gly Leu Ala Ile Gly Ile Met Met Leu Lys Leu
1250 1255 1260
Leu Thr Asp Phe Gln Ser His Gln Leu Trp Ala Thr Leu Leu Ser
1265 1270 1275
Leu Thr Phe Ile Lys Thr Thr Phe Ser Leu His Tyr Ala Trp Lys
1280 1285 1290
Thr Met Ala Met Val Leu Ser Ile Val Ser Leu Phe Pro Leu Cys
1295 1300 1305
Leu Ser Thr Thr Ser Gln Lys Thr Thr Trp Leu Pro Val Leu Leu
1310 1315 1320
Gly Ser Leu Gly Cys Lys Pro Leu Pro Met Phe Leu Ile Thr Glu
1325 1330 1335
Asn Lys Ile Trp Gly Arg Lys Ser Trp Pro Leu Asn Glu Gly Ile
1340 1345 1350
Met Ala Val Gly Ile Val Ser Ile Leu Leu Ser Ser Leu Leu Lys
1355 1360 1365
Asn Asp Val Pro Leu Ala Gly Pro Leu Ile Ala Gly Gly Met Leu
1370 1375 1380
Ile Ala Cys Tyr Val Ile Ser Gly Ser Ser Ala Asp Leu Ser Leu
1385 1390 1395
Glu Lys Ala Ala Glu Val Ser Trp Glu Glu Glu Ala Glu His Ser
1400 1405 1410
Gly Ala Ser His Asn Ile Leu Val Glu Val Gln Asp Asp Gly Thr
1415 1420 1425
Met Lys Ile Lys Asp Glu Glu Arg Asp Asp Thr Leu Thr Ile Leu
1430 1435 1440
Leu Lys Ala Thr Leu Leu Ala Val Ser Gly Val Tyr Pro Met Ser
1445 1450 1455
Ile Pro Ala Thr Leu Phe Val Trp Tyr Phe Trp Gln Lys Lys Lys
1460 1465 1470
Gln Arg Ser Gly Val Leu Trp Asp Thr Pro Ser Pro Pro Glu Val
1475 1480 1485
Glu Arg Ala Val Leu Asp Asp Gly Ile Tyr Arg Ile Leu Gln Arg
1490 1495 1500
Gly Leu Leu Gly Arg Ser Gln Val Gly Val Gly Val Phe Gln Glu
1505 1510 1515
Gly Val Phe His Thr Met Trp His Val Thr Arg Gly Ala Val Leu
1520 1525 1530
Met Tyr Gln Gly Lys Arg Leu Glu Pro Ser Trp Ala Ser Val Lys
1535 1540 1545
Lys Asp Leu Ile Ser Tyr Gly Gly Gly Trp Arg Phe Gln Gly Ser
1550 1555 1560
Trp Asn Thr Gly Glu Glu Val Gln Val Ile Ala Val Glu Pro Gly
1565 1570 1575
Lys Asn Pro Lys Asn Val Gln Thr Thr Pro Gly Thr Phe Lys Thr
1580 1585 1590
Pro Glu Gly Glu Val Gly Ala Ile Ala Leu Asp Phe Lys Pro Gly
1595 1600 1605
Thr Ser Gly Ser Pro Ile Val Asn Arg Glu Gly Lys Ile Val Gly
1610 1615 1620
Leu Tyr Gly Asn Gly Val Val Thr Thr Ser Gly Thr Tyr Val Ser
1625 1630 1635
Ala Ile Ala Gln Ala Lys Ala Ser Gln Glu Gly Pro Leu Pro Glu
1640 1645 1650
Ile Glu Asp Glu Val Phe Arg Lys Arg Asn Leu Thr Ile Met Asp
1655 1660 1665
Leu His Pro Gly Ser Gly Lys Thr Arg Arg Tyr Leu Pro Ala Ile
1670 1675 1680
Val Arg Glu Ala Ile Lys Arg Lys Leu Arg Thr Leu Ile Leu Ala
1685 1690 1695
Pro Thr Arg Val Val Ala Ser Glu Met Ala Glu Ala Leu Lys Gly
1700 1705 1710
Val Pro Ile Arg Tyr Gln Thr Thr Ala Val Lys Ser Glu His Thr
1715 1720 1725
Gly Lys Glu Ile Val Asp Leu Met Cys His Ala Thr Phe Thr Met
1730 1735 1740
Arg Leu Leu Ser Pro Val Arg Val Pro Asn Tyr Asn Met Ile Ile
1745 1750 1755
Met Asp Glu Ala His Phe Thr Asp Pro Ala Ser Ile Ala Ala Arg
1760 1765 1770
Gly Tyr Ile Ser Thr Arg Val Gly Met Gly Glu Ala Ala Ala Ile
1775 1780 1785
Phe Met Thr Ala Thr Pro Pro Gly Ser Val Glu Ala Phe Pro Gln
1790 1795 1800
Ser Asn Ala Ile Ile Gln Asp Glu Glu Arg Asp Ile Pro Glu Arg
1805 1810 1815
Ser Trp Asn Ser Gly Tyr Asp Trp Ile Thr Asp Phe Pro Gly Lys
1820 1825 1830
Thr Val Trp Phe Val Pro Ser Ile Lys Ser Gly Asn Asp Ile Ala
1835 1840 1845
Asn Cys Leu Arg Lys Asn Gly Lys Arg Val Ile Gln Leu Ser Arg
1850 1855 1860
Lys Thr Phe Asp Thr Glu Tyr Gln Lys Thr Lys Asn Asn Asp Trp
1865 1870 1875
Asp Tyr Val Val Thr Thr Asp Ile Ser Glu Met Gly Ala Asn Phe
1880 1885 1890
Arg Ala Asp Arg Val Ile Asp Pro Arg Arg Cys Leu Lys Pro Val
1895 1900 1905
Ile Leu Lys Asp Gly Pro Glu Arg Val Ile Leu Ala Gly Pro Met
1910 1915 1920
Pro Val Thr Val Ala Ser Ala Ala Gln Arg Arg Gly Arg Ile Gly
1925 1930 1935
Arg Asn Gln Asn Lys Glu Gly Asp Gln Tyr Ile Tyr Met Gly Gln
1940 1945 1950
Pro Leu Asn Asn Asp Glu Asp His Ala His Trp Thr Glu Ala Lys
1955 1960 1965
Met Leu Leu Asp Asn Ile Asn Thr Pro Glu Gly Ile Ile Pro Ala
1970 1975 1980
Leu Tyr Glu Pro Glu Arg Glu Lys Ser Ala Ala Ile Asp Gly Glu
1985 1990 1995
Tyr Arg Leu Arg Gly Glu Ala Arg Lys Thr Phe Val Glu Leu Met
2000 2005 2010
Arg Arg Gly Asp Leu Pro Val Trp Leu Ser Tyr Lys Val Ala Ser
2015 2020 2025
Glu Gly Phe Gln Tyr Ser Asp Arg Arg Trp Cys Phe Asp Gly Glu
2030 2035 2040
Arg Asn Asn Gln Val Leu Glu Glu Asn Met Asp Val Glu Ile Trp
2045 2050 2055
Thr Lys Glu Gly Glu Arg Lys Lys Leu Arg Pro Arg Trp Leu Asp
2060 2065 2070
Ala Arg Thr Tyr Ser Asp Pro Leu Ala Leu Arg Glu Phe Lys Glu
2075 2080 2085
Phe Ala Ala Gly Arg Arg Ser Val Ser Gly Asp Leu Ile Leu Glu
2090 2095 2100
Ile Gly Lys Leu Pro Gln His Leu Thr Gln Arg Ala Gln Asn Ala
2105 2110 2115
Leu Asp Asn Leu Val Met Leu His Asn Ser Glu Gln Gly Gly Lys
2120 2125 2130
Ala Tyr Arg His Ala Met Glu Glu Leu Pro Asp Thr Ile Glu Thr
2135 2140 2145
Leu Met Leu Leu Ala Leu Ile Ala Val Leu Thr Gly Gly Val Thr
2150 2155 2160
Leu Phe Phe Leu Ser Gly Arg Gly Leu Gly Lys Thr Ser Ile Gly
2165 2170 2175
Leu Leu Cys Val Met Ala Ser Ser Ala Leu Leu Trp Met Ala Ser
2180 2185 2190
Val Glu Pro His Trp Ile Ala Ala Ser Ile Ile Leu Glu Phe Phe
2195 2200 2205
Leu Met Val Leu Leu Ile Pro Glu Pro Asp Arg Gln Arg Thr Pro
2210 2215 2220
Gln Asp Asn Gln Leu Ala Tyr Val Val Ile Gly Leu Leu Phe Met
2225 2230 2235
Ile Leu Thr Val Ala Ala Asn Glu Met Gly Leu Leu Glu Thr Thr
2240 2245 2250
Lys Lys Asp Leu Gly Ile Gly His Val Ala Ala Glu Asn His His
2255 2260 2265
His Ala Thr Met Leu Asp Val Asp Leu His Pro Ala Ser Ala Trp
2270 2275 2280
Thr Leu Tyr Ala Val Ala Thr Thr Ile Ile Thr Pro Met Met Arg
2285 2290 2295
His Thr Ile Glu Asn Thr Thr Ala Asn Ile Ser Leu Thr Ala Ile
2300 2305 2310
Ala Asn Gln Ala Ala Ile Leu Met Gly Leu Asp Lys Gly Trp Pro
2315 2320 2325
Ile Ser Lys Met Asp Ile Gly Val Pro Leu Leu Ala Leu Gly Cys
2330 2335 2340
Tyr Ser Gln Val Asn Pro Leu Thr Leu Ile Ala Ala Val Leu Met
2345 2350 2355
Leu Val Ala His Tyr Ala Ile Ile Gly Pro Gly Leu Gln Ala Lys
2360 2365 2370
Ala Thr Arg Glu Ala Gln Lys Arg Thr Ala Ala Gly Ile Met Lys
2375 2380 2385
Asn Pro Thr Val Asp Gly Ile Val Ala Ile Asp Leu Asp Pro Val
2390 2395 2400
Val Tyr Asp Ala Lys Phe Glu Lys Gln Leu Gly Gln Ile Met Leu
2405 2410 2415
Leu Ile Leu Cys Thr Ser Gln Ile Leu Leu Met Arg Thr Thr Trp
2420 2425 2430
Ala Leu Cys Glu Ser Ile Thr Leu Ala Thr Gly Pro Leu Thr Thr
2435 2440 2445
Leu Trp Glu Gly Ser Pro Gly Lys Phe Trp Asn Thr Thr Ile Ala
2450 2455 2460
Val Ser Met Ala Asn Ile Phe Arg Gly Ser Tyr Leu Ala Gly Ala
2465 2470 2475
Gly Leu Ala Phe Ser Leu Met Lys Ser Leu Gly Gly Gly Arg Arg
2480 2485 2490
Gly Thr Gly Ala Gln Gly Glu Thr Leu Gly Glu Lys Trp Lys Arg
2495 2500 2505
Gln Leu Asn Gln Leu Ser Lys Ser Glu Phe Asn Thr Tyr Lys Arg
2510 2515 2520
Ser Gly Ile Met Glu Val Asp Arg Ser Glu Ala Lys Glu Gly Leu
2525 2530 2535
Lys Arg Gly Glu Thr Thr Lys His Ala Val Ser Arg Gly Thr Ala
2540 2545 2550
Lys Leu Arg Trp Phe Val Glu Arg Asn Leu Val Lys Pro Glu Gly
2555 2560 2565
Lys Val Ile Asp Leu Gly Cys Gly Arg Gly Gly Trp Ser Tyr Tyr
2570 2575 2580
Cys Ala Gly Leu Lys Lys Val Thr Glu Val Lys Gly Tyr Thr Lys
2585 2590 2595
Gly Gly Pro Gly His Glu Glu Pro Ile Pro Met Ala Thr Tyr Gly
2600 2605 2610
Trp Asn Leu Val Lys Leu His Ser Gly Lys Asp Val Phe Phe Ile
2615 2620 2625
Pro Pro Glu Lys Cys Asp Thr Leu Leu Cys Asp Ile Gly Glu Ser
2630 2635 2640
Ser Pro Asn Pro Thr Ile Glu Glu Gly Arg Thr Leu Arg Val Leu
2645 2650 2655
Lys Met Val Glu Pro Trp Leu Arg Gly Asn Gln Phe Cys Ile Lys
2660 2665 2670
Ile Leu Asn Pro Tyr Met Pro Ser Val Val Glu Thr Leu Glu Gln
2675 2680 2685
Met Gln Arg Lys His Gly Gly Met Leu Val Arg Asn Pro Leu Ser
2690 2695 2700
Arg Asn Ser Thr His Glu Met Tyr Trp Val Ser Cys Gly Thr Gly
2705 2710 2715
Asn Ile Val Ser Ala Val Asn Met Thr Ser Arg Met Leu Leu Asn
2720 2725 2730
Arg Phe Thr Met Ala His Arg Lys Pro Thr Tyr Glu Arg Asp Val
2735 2740 2745
Asp Leu Gly Ala Gly Thr Arg His Val Ala Val Glu Pro Glu Val
2750 2755 2760
Ala Asn Leu Asp Ile Ile Gly Gln Arg Ile Glu Asn Ile Lys Asn
2765 2770 2775
Glu His Lys Ser Thr Trp His Tyr Asp Glu Asp Asn Pro Tyr Lys
2780 2785 2790
Thr Trp Ala Tyr His Gly Ser Tyr Glu Val Lys Pro Ser Gly Ser
2795 2800 2805
Ala Ser Ser Met Val Asn Gly Val Val Arg Leu Leu Thr Lys Pro
2810 2815 2820
Trp Asp Val Ile Pro Met Val Thr Gln Ile Ala Met Thr Asp Thr
2825 2830 2835
Thr Pro Phe Gly Gln Gln Arg Val Phe Lys Glu Lys Val Asp Thr
2840 2845 2850
Arg Thr Pro Lys Ala Lys Arg Gly Thr Ala Gln Ile Met Glu Val
2855 2860 2865
Thr Ala Arg Trp Leu Trp Gly Phe Leu Ser Arg Asn Lys Lys Pro
2870 2875 2880
Arg Ile Cys Thr Arg Glu Glu Phe Thr Arg Lys Val Arg Ser Asn
2885 2890 2895
Ala Ala Ile Gly Ala Val Phe Val Asp Glu Asn Gln Trp Asn Ser
2900 2905 2910
Ala Lys Glu Ala Val Glu Asp Glu Arg Phe Trp Glu Leu Val His
2915 2920 2925
Arg Glu Arg Glu Leu His Lys Gln Gly Lys Cys Ala Thr Cys Val
2930 2935 2940
Tyr Asn Met Met Gly Lys Arg Glu Lys Lys Leu Gly Glu Phe Gly
2945 2950 2955
Lys Ala Lys Gly Ser Arg Ala Ile Trp Tyr Met Trp Leu Gly Ala
2960 2965 2970
Arg Phe Leu Glu Phe Glu Ala Leu Gly Phe Met Asn Glu Asp His
2975 2980 2985
Trp Phe Ser Arg Glu Asn Ser Leu Ser Gly Val Glu Gly Glu Gly
2990 2995 3000
Leu His Lys Leu Gly Tyr Ile Leu Arg Asp Ile Ser Arg Ile Pro
3005 3010 3015
Gly Gly Asn Met Tyr Ala Asp Asp Thr Ala Gly Trp Asp Thr Arg
3020 3025 3030
Ile Thr Glu Asp Asp Leu Gln Asn Glu Ala Lys Ile Thr Asp Ile
3035 3040 3045
Met Glu Pro Glu His Ala Leu Leu Ala Thr Ser Ile Phe Lys Leu
3050 3055 3060
Thr Tyr Gln Asn Lys Val Val Arg Val Gln Arg Pro Ala Lys Asn
3065 3070 3075
Gly Thr Val Met Asp Val Ile Ser Arg Arg Asp Gln Arg Gly Ser
3080 3085 3090
Gly Gln Val Gly Thr Tyr Gly Leu Asn Thr Phe Thr Asn Met Glu
3095 3100 3105
Ala Gln Leu Ile Arg Gln Met Glu Ser Glu Gly Ile Phe Leu Pro
3110 3115 3120
Ser Glu Leu Glu Thr Pro Asn Leu Ala Gly Arg Val Leu Asp Trp
3125 3130 3135
Leu Glu Lys Tyr Gly Val Glu Arg Leu Lys Arg Met Ala Ile Ser
3140 3145 3150
Gly Asp Asp Cys Val Val Lys Pro Ile Asp Asp Arg Phe Ala Thr
3155 3160 3165
Ala Leu Thr Ala Leu Asn Asp Met Gly Lys Val Arg Lys Asp Ile
3170 3175 3180
Pro Gln Trp Glu Pro Ser Lys Gly Trp Asn Asp Trp Gln Gln Val
3185 3190 3195
Pro Phe Cys Ser His His Phe His Gln Leu Ile Met Lys Asp Gly
3200 3205 3210
Arg Glu Ile Val Val Pro Cys Arg Asn Gln Asp Glu Leu Val Gly
3215 3220 3225
Arg Ala Arg Val Ser Gln Gly Ala Gly Trp Ser Leu Arg Glu Thr
3230 3235 3240
Ala Cys Leu Gly Lys Ser Tyr Ala Gln Met Trp Gln Leu Met Tyr
3245 3250 3255
Phe His Arg Arg Asp Leu Arg Leu Ala Ala Asn Ala Ile Cys Ser
3260 3265 3270
Ala Val Pro Val Asp Trp Val Pro Thr Ser Arg Thr Thr Trp Ser
3275 3280 3285
Ile His Ala His His Gln Trp Met Thr Thr Glu Asp Met Leu Ser
3290 3295 3300
Val Trp Asn Arg Val Trp Ile Glu Glu Asn Pro Trp Met Glu Asp
3305 3310 3315
Lys Thr His Val Ser Ser Trp Glu Glu Val Pro Tyr Leu Gly Lys
3320 3325 3330
Arg Glu Asp Gln Trp Cys Gly Ser Leu Ile Gly Leu Thr Ala Arg
3335 3340 3345
Ala Thr Trp Ala Thr Asn Ile Gln Val Ala Ile Asn Gln Val Arg
3350 3355 3360
Arg Leu Ile Gly Asn Glu Asn Tyr Leu Asp Tyr Met Thr Ser Met
3365 3370 3375
Lys Arg Phe Lys Asn Glu Ser Asp Pro Glu Gly Ala Leu Trp
3380 3385 3390
<210> 5
<211> 10723
<212> DNA
<213> 2型登革病毒
<220>
<221> CDS
<222> (97)..(10272)
<400> 5
agttgttagt ctacgtggac cgacaaagac agattctttg agggagctaa gctcaacgta 60
gttctaacag ttttttaatt agagagcaga tctctg atg aat aac caa cgg aaa 114
Met Asn Asn Gln Arg Lys
1 5
aag gcg aaa aac acg cct ttc aat atg ctg aaa cgc gag aga aac cgc 162
Lys Ala Lys Asn Thr Pro Phe Asn Met Leu Lys Arg Glu Arg Asn Arg
10 15 20
gtg tcg act gtg caa cag ctg aca aag aga ttc tca ctt gga atg ctg 210
Val Ser Thr Val Gln Gln Leu Thr Lys Arg Phe Ser Leu Gly Met Leu
25 30 35
cag gga cga gga cca tta aaa ctg ttc atg gcc ctg gtg gcg ttc ctt 258
Gln Gly Arg Gly Pro Leu Lys Leu Phe Met Ala Leu Val Ala Phe Leu
40 45 50
cgt ttc cta aca atc cca cca aca gca ggg ata ttg aag aga tgg gga 306
Arg Phe Leu Thr Ile Pro Pro Thr Ala Gly Ile Leu Lys Arg Trp Gly
55 60 65 70
aca att aaa aaa tca aaa gct att aat gtt ttg aga ggg ttc agg aaa 354
Thr Ile Lys Lys Ser Lys Ala Ile Asn Val Leu Arg Gly Phe Arg Lys
75 80 85
gag att gga agg atg ctg aac atc ttg aat agg aga cgc aga tct gca 402
Glu Ile Gly Arg Met Leu Asn Ile Leu Asn Arg Arg Arg Arg Ser Ala
90 95 100
ggc atg atc att atg ctg att cca aca gtg atg gcg ttc cat tta acc 450
Gly Met Ile Ile Met Leu Ile Pro Thr Val Met Ala Phe His Leu Thr
105 110 115
aca cgt aac gga gaa cca cac atg atc gtc agc aga caa gag aaa ggg 498
Thr Arg Asn Gly Glu Pro His Met Ile Val Ser Arg Gln Glu Lys Gly
120 125 130
aaa agt ctt ctg ttt aaa aca gag gat ggc gtg aac atg tgt acc ctc 546
Lys Ser Leu Leu Phe Lys Thr Glu Asp Gly Val Asn Met Cys Thr Leu
135 140 145 150
atg gcc atg gac ctt ggt gaa ttg tgt gaa gac aca atc acg tac aag 594
Met Ala Met Asp Leu Gly Glu Leu Cys Glu Asp Thr Ile Thr Tyr Lys
155 160 165
tgt ccc ctt ctc agg cag aat gag cca gaa gac ata gac tgt tgg tgc 642
Cys Pro Leu Leu Arg Gln Asn Glu Pro Glu Asp Ile Asp Cys Trp Cys
170 175 180
aac tct acg tcc acg tgg gta act tat ggg acg tgt acc acc atg gga 690
Asn Ser Thr Ser Thr Trp Val Thr Tyr Gly Thr Cys Thr Thr Met Gly
185 190 195
gaa cat aga aga gaa aaa aga tca gtg gca ctc gtt cca cat gtg gga 738
Glu His Arg Arg Glu Lys Arg Ser Val Ala Leu Val Pro His Val Gly
200 205 210
atg gga ctg gag aca cga act gaa aca tgg atg tca tca gaa ggg gcc 786
Met Gly Leu Glu Thr Arg Thr Glu Thr Trp Met Ser Ser Glu Gly Ala
215 220 225 230
tgg aaa cat gtc cag aga att gaa act tgg atc ttg aga cat cca ggc 834
Trp Lys His Val Gln Arg Ile Glu Thr Trp Ile Leu Arg His Pro Gly
235 240 245
ttc acc atg atg gca gca atc ctg gca tac acc ata gga acg aca cat 882
Phe Thr Met Met Ala Ala Ile Leu Ala Tyr Thr Ile Gly Thr Thr His
250 255 260
ttc caa aga gcc ctg att ttc atc tta ctg aca gct gtc act cct tca 930
Phe Gln Arg Ala Leu Ile Phe Ile Leu Leu Thr Ala Val Thr Pro Ser
265 270 275
atg aca atg cgt tgc ata gga atg tca aat aga gac ttt gtg gaa ggg 978
Met Thr Met Arg Cys Ile Gly Met Ser Asn Arg Asp Phe Val Glu Gly
280 285 290
gtt tca gga gga agc tgg gtt gac ata gtc tta gaa cat gga agc tgt 1026
Val Ser Gly Gly Ser Trp Val Asp Ile Val Leu Glu His Gly Ser Cys
295 300 305 310
gtg acg acg atg gca aaa aac aaa cca aca ttg gat ttt gaa ctg ata 1074
Val Thr Thr Met Ala Lys Asn Lys Pro Thr Leu Asp Phe Glu Leu Ile
315 320 325
aaa aca gaa gcc aaa cag cct gcc acc cta agg aag tac tgt ata gag 1122
Lys Thr Glu Ala Lys Gln Pro Ala Thr Leu Arg Lys Tyr Cys Ile Glu
330 335 340
gca aag cta acc aac aca aca aca gaa tct cgc tgc cca aca caa ggg 1170
Ala Lys Leu Thr Asn Thr Thr Thr Glu Ser Arg Cys Pro Thr Gln Gly
345 350 355
gaa ccc agc cta aat gaa gag cag gac aaa agg ttc gtc tgc aaa cac 1218
Glu Pro Ser Leu Asn Glu Glu Gln Asp Lys Arg Phe Val Cys Lys His
360 365 370
tcc atg gta gac aga gga tgg gga aat gga tgt gga cta ttt gga aag 1266
Ser Met Val Asp Arg Gly Trp Gly Asn Gly Cys Gly Leu Phe Gly Lys
375 380 385 390
gga ggc att gtg acc tgt gct atg ttc aga tgc aaa aag aac atg gaa 1314
Gly Gly Ile Val Thr Cys Ala Met Phe Arg Cys Lys Lys Asn Met Glu
395 400 405
gga aaa gtt gtg caa cca gaa aac ttg gaa tac acc att gtg ata aca 1362
Gly Lys Val Val Gln Pro Glu Asn Leu Glu Tyr Thr Ile Val Ile Thr
410 415 420
cct cac tca ggg gaa gag cat gca gtc gga aat gac aca gga aaa cat 1410
Pro His Ser Gly Glu Glu His Ala Val Gly Asn Asp Thr Gly Lys His
425 430 435
ggc aag gaa atc aaa ata aca cca cag agt tcc atc aca gaa gca gaa 1458
Gly Lys Glu Ile Lys Ile Thr Pro Gln Ser Ser Ile Thr Glu Ala Glu
440 445 450
ttg aca ggt tat ggc act gtc aca atg gag tgc tct cca aga acg ggc 1506
Leu Thr Gly Tyr Gly Thr Val Thr Met Glu Cys Ser Pro Arg Thr Gly
455 460 465 470
ctc gac ttc aat gag atg gtg ttg ctg cag atg gaa aat aaa gct tgg 1554
Leu Asp Phe Asn Glu Met Val Leu Leu Gln Met Glu Asn Lys Ala Trp
475 480 485
ctg gtg cac agg caa tgg ttc cta gac ctg ccg tta cca tgg ttg ccc 1602
Leu Val His Arg Gln Trp Phe Leu Asp Leu Pro Leu Pro Trp Leu Pro
490 495 500
gga gcg gac aca caa ggg tca aat tgg ata cag aaa gag aca ttg gtc 1650
Gly Ala Asp Thr Gln Gly Ser Asn Trp Ile Gln Lys Glu Thr Leu Val
505 510 515
act ttc aaa aat ccc cat gcg aag aaa cag gat gtt gtt gtt tta gga 1698
Thr Phe Lys Asn Pro His Ala Lys Lys Gln Asp Val Val Val Leu Gly
520 525 530
tcc caa gaa ggg gcc atg cac aca gca ctt aca ggg gcc aca gaa atc 1746
Ser Gln Glu Gly Ala Met His Thr Ala Leu Thr Gly Ala Thr Glu Ile
535 540 545 550
caa atg tca tca gga aac tta ctc ttc aca gga cat ctc aag tgc agg 1794
Gln Met Ser Ser Gly Asn Leu Leu Phe Thr Gly His Leu Lys Cys Arg
555 560 565
ctg aga atg gac aag cta cag ctc aaa gga atg tca tac tct atg tgc 1842
Leu Arg Met Asp Lys Leu Gln Leu Lys Gly Met Ser Tyr Ser Met Cys
570 575 580
aca gga aag ttt aaa gtt gtg aag gaa ata gca gaa aca caa cat gga 1890
Thr Gly Lys Phe Lys Val Val Lys Glu Ile Ala Glu Thr Gln His Gly
585 590 595
aca ata gtt atc aga gtg caa tat gaa ggg gac ggc tct cca tgc aag 1938
Thr Ile Val Ile Arg Val Gln Tyr Glu Gly Asp Gly Ser Pro Cys Lys
600 605 610
atc cct ttt gag ata atg gat ttg gaa aaa aga cat gtc tta ggt cgc 1986
Ile Pro Phe Glu Ile Met Asp Leu Glu Lys Arg His Val Leu Gly Arg
615 620 625 630
ctg att aca gtc aac cca att gtg aca gaa aaa gat agc cca gtc aac 2034
Leu Ile Thr Val Asn Pro Ile Val Thr Glu Lys Asp Ser Pro Val Asn
635 640 645
ata gaa gca gaa cct cca ttc gga gac agc tac atc atc ata gga gta 2082
Ile Glu Ala Glu Pro Pro Phe Gly Asp Ser Tyr Ile Ile Ile Gly Val
650 655 660
gag ccg gga caa ctg aag ctc aac tgg ttt aag aaa gga agt tct atc 2130
Glu Pro Gly Gln Leu Lys Leu Asn Trp Phe Lys Lys Gly Ser Ser Ile
665 670 675
ggc caa atg ttt gag aca aca atg agg ggg gcg aag aga atg gcc att 2178
Gly Gln Met Phe Glu Thr Thr Met Arg Gly Ala Lys Arg Met Ala Ile
680 685 690
tta ggt gac aca gcc tgg gat ttt gga tcc ttg gga gga gtg ttt aca 2226
Leu Gly Asp Thr Ala Trp Asp Phe Gly Ser Leu Gly Gly Val Phe Thr
695 700 705 710
tct ata gga aag gct ctc cac caa gtc ttt gga gca atc tat gga gct 2274
Ser Ile Gly Lys Ala Leu His Gln Val Phe Gly Ala Ile Tyr Gly Ala
715 720 725
gcc ttc agt ggg gtt tca tgg act atg aaa atc ctc ata gga gtc att 2322
Ala Phe Ser Gly Val Ser Trp Thr Met Lys Ile Leu Ile Gly Val Ile
730 735 740
atc aca tgg ata gga atg aat tca cgc agc acc tca ctg tct gtg aca 2370
Ile Thr Trp Ile Gly Met Asn Ser Arg Ser Thr Ser Leu Ser Val Thr
745 750 755
cta gta ttg gtg gga att gtg aca ctg tat ttg gga gtc atg gtg cag 2418
Leu Val Leu Val Gly Ile Val Thr Leu Tyr Leu Gly Val Met Val Gln
760 765 770
gcc gat agt ggt tgc gtt gtg agc tgg aaa aac aaa gaa ctg aaa tgt 2466
Ala Asp Ser Gly Cys Val Val Ser Trp Lys Asn Lys Glu Leu Lys Cys
775 780 785 790
ggc agt ggg att ttc atc aca gac aac gtg cac aca tgg aca gaa caa 2514
Gly Ser Gly Ile Phe Ile Thr Asp Asn Val His Thr Trp Thr Glu Gln
795 800 805
tac aag ttc caa cca gaa tcc cct tca aaa cta gct tca gct atc cag 2562
Tyr Lys Phe Gln Pro Glu Ser Pro Ser Lys Leu Ala Ser Ala Ile Gln
810 815 820
aaa gcc cat gaa gag ggc att tgt gga atc cgc tca gta aca aga ctg 2610
Lys Ala His Glu Glu Gly Ile Cys Gly Ile Arg Ser Val Thr Arg Leu
825 830 835
gag aat ctg atg tgg aaa caa ata aca cca gaa ttg aat cac att cta 2658
Glu Asn Leu Met Trp Lys Gln Ile Thr Pro Glu Leu Asn His Ile Leu
840 845 850
tca gaa aat gag gtg aag tta act att atg aca gga gac atc aaa gga 2706
Ser Glu Asn Glu Val Lys Leu Thr Ile Met Thr Gly Asp Ile Lys Gly
855 860 865 870
atc atg cag gca gga aaa cga tct ctg cgg cct cag ccc act gag ctg 2754
Ile Met Gln Ala Gly Lys Arg Ser Leu Arg Pro Gln Pro Thr Glu Leu
875 880 885
aag tat tca tgg aaa aca tgg ggc aaa gca aaa atg ctc tct aca gag 2802
Lys Tyr Ser Trp Lys Thr Trp Gly Lys Ala Lys Met Leu Ser Thr Glu
890 895 900
tct cat aac cag acc ttt ctc att gat ggc ccc gaa aca gca gaa tgc 2850
Ser His Asn Gln Thr Phe Leu Ile Asp Gly Pro Glu Thr Ala Glu Cys
905 910 915
ccc aac aca aat aga gct tgg aat tcg ttg gaa gtt gaa gac tat ggc 2898
Pro Asn Thr Asn Arg Ala Trp Asn Ser Leu Glu Val Glu Asp Tyr Gly
920 925 930
ttt gga gta ttc acc acc aat ata tgg cta aaa ttg aaa gaa aaa cag 2946
Phe Gly Val Phe Thr Thr Asn Ile Trp Leu Lys Leu Lys Glu Lys Gln
935 940 945 950
gat gta ttc tgc gac tca aaa ctc atg tca gcg gcc ata aaa gac aac 2994
Asp Val Phe Cys Asp Ser Lys Leu Met Ser Ala Ala Ile Lys Asp Asn
955 960 965
aga gcc gtc cat gcc gat atg ggt tat tgg ata gaa agt gca ctc aat 3042
Arg Ala Val His Ala Asp Met Gly Tyr Trp Ile Glu Ser Ala Leu Asn
970 975 980
gac aca tgg aag ata gag aaa gcc tct ttc att gaa gtt aaa aac tgc 3090
Asp Thr Trp Lys Ile Glu Lys Ala Ser Phe Ile Glu Val Lys Asn Cys
985 990 995
cac tgg cca aaa tca cac acc ctc tgg agc aat gga gtg cta gaa 3135
His Trp Pro Lys Ser His Thr Leu Trp Ser Asn Gly Val Leu Glu
1000 1005 1010
agt gag atg ata att cca aag aat ctc gct gga cca gtg tct caa 3180
Ser Glu Met Ile Ile Pro Lys Asn Leu Ala Gly Pro Val Ser Gln
1015 1020 1025
cac aac tat aga cca ggc tac cat aca caa ata aca gga cca tgg 3225
His Asn Tyr Arg Pro Gly Tyr His Thr Gln Ile Thr Gly Pro Trp
1030 1035 1040
cat cta ggt aag ctt gag atg gac ttt gat ttc tgt gat gga aca 3270
His Leu Gly Lys Leu Glu Met Asp Phe Asp Phe Cys Asp Gly Thr
1045 1050 1055
aca gtg gta gtg act gag gac tgc gga aat aga gga ccc tct ttg 3315
Thr Val Val Val Thr Glu Asp Cys Gly Asn Arg Gly Pro Ser Leu
1060 1065 1070
aga aca acc act gcc tct gga aaa ctc ata aca gaa tgg tgc tgc 3360
Arg Thr Thr Thr Ala Ser Gly Lys Leu Ile Thr Glu Trp Cys Cys
1075 1080 1085
cga tct tgc aca tta cca ccg cta aga tac aga ggt gag gat ggg 3405
Arg Ser Cys Thr Leu Pro Pro Leu Arg Tyr Arg Gly Glu Asp Gly
1090 1095 1100
tgc tgg tac ggg atg gaa atc aga cca ttg aag gag aaa gaa gag 3450
Cys Trp Tyr Gly Met Glu Ile Arg Pro Leu Lys Glu Lys Glu Glu
1105 1110 1115
aat ttg gtc aac tcc ttg gtc aca gct gga cat ggg cag gtc gac 3495
Asn Leu Val Asn Ser Leu Val Thr Ala Gly His Gly Gln Val Asp
1120 1125 1130
aac ttt tca cta gga gtc ttg gga atg gca ttg ttc ctg gag gaa 3540
Asn Phe Ser Leu Gly Val Leu Gly Met Ala Leu Phe Leu Glu Glu
1135 1140 1145
atg ctt agg acc cga gta gga acg aaa cat gca ata cta cta gtt 3585
Met Leu Arg Thr Arg Val Gly Thr Lys His Ala Ile Leu Leu Val
1150 1155 1160
gca gtt tct ttt gtg aca ttg atc aca ggg aac atg tcc ttt aga 3630
Ala Val Ser Phe Val Thr Leu Ile Thr Gly Asn Met Ser Phe Arg
1165 1170 1175
gac ctg gga aga gtg atg gtt atg gta ggc gcc act atg acg gat 3675
Asp Leu Gly Arg Val Met Val Met Val Gly Ala Thr Met Thr Asp
1180 1185 1190
gac ata ggt atg ggc gtg act tat ctt gcc cta cta gca gcc ttc 3720
Asp Ile Gly Met Gly Val Thr Tyr Leu Ala Leu Leu Ala Ala Phe
1195 1200 1205
aaa gtc aga cca act ttt gca gct gga cta ctc ttg aga aag ctg 3765
Lys Val Arg Pro Thr Phe Ala Ala Gly Leu Leu Leu Arg Lys Leu
1210 1215 1220
acc tcc aag gaa ttg atg atg act act ata gga att gta ctc ctc 3810
Thr Ser Lys Glu Leu Met Met Thr Thr Ile Gly Ile Val Leu Leu
1225 1230 1235
tcc cag agc acc ata cca gag acc att ctt gag ttg act gat gcg 3855
Ser Gln Ser Thr Ile Pro Glu Thr Ile Leu Glu Leu Thr Asp Ala
1240 1245 1250
tta gcc tta ggc atg atg gtc ctc aaa atg gtg aga aat atg gaa 3900
Leu Ala Leu Gly Met Met Val Leu Lys Met Val Arg Asn Met Glu
1255 1260 1265
aag tat caa ttg gca gtg act atc atg gct atc ttg tgc gtc cca 3945
Lys Tyr Gln Leu Ala Val Thr Ile Met Ala Ile Leu Cys Val Pro
1270 1275 1280
aac gca gtg ata tta caa aac gca tgg aaa gtg agt tgc aca ata 3990
Asn Ala Val Ile Leu Gln Asn Ala Trp Lys Val Ser Cys Thr Ile
1285 1290 1295
ttg gca gtg gtg tcc gtt tcc cca ctg ctc tta aca tcc tca cag 4035
Leu Ala Val Val Ser Val Ser Pro Leu Leu Leu Thr Ser Ser Gln
1300 1305 1310
caa aaa aca gat tgg ata cca tta gca ttg acg atc aaa ggt ctc 4080
Gln Lys Thr Asp Trp Ile Pro Leu Ala Leu Thr Ile Lys Gly Leu
1315 1320 1325
aat cca aca gct att ttt cta aca acc ctc tca aga acc agc aag 4125
Asn Pro Thr Ala Ile Phe Leu Thr Thr Leu Ser Arg Thr Ser Lys
1330 1335 1340
aaa agg agc tgg cca tta aat gag gct atc atg gca gtc ggg atg 4170
Lys Arg Ser Trp Pro Leu Asn Glu Ala Ile Met Ala Val Gly Met
1345 1350 1355
gtg agc att tta gcc agt tct ctc cta aaa aat gat att ccc atg 4215
Val Ser Ile Leu Ala Ser Ser Leu Leu Lys Asn Asp Ile Pro Met
1360 1365 1370
aca gga cca tta gtg gct gga ggg ctc ctc act gtg tgc tac gtg 4260
Thr Gly Pro Leu Val Ala Gly Gly Leu Leu Thr Val Cys Tyr Val
1375 1380 1385
ctc act gga cga tcg gcc gat ttg gaa ctg gag aga gca gcc gat 4305
Leu Thr Gly Arg Ser Ala Asp Leu Glu Leu Glu Arg Ala Ala Asp
1390 1395 1400
gtc aaa tgg gaa gac cag gca gag ata tca gga agc agt cca atc 4350
Val Lys Trp Glu Asp Gln Ala Glu Ile Ser Gly Ser Ser Pro Ile
1405 1410 1415
ctg tca ata aca ata tca gaa gat ggt agc atg tcg ata aaa aat 4395
Leu Ser Ile Thr Ile Ser Glu Asp Gly Ser Met Ser Ile Lys Asn
1420 1425 1430
gaa gag gaa gaa caa aca ctg acc ata ctc att aga aca gga ttg 4440
Glu Glu Glu Glu Gln Thr Leu Thr Ile Leu Ile Arg Thr Gly Leu
1435 1440 1445
ctg gtg atc tca gga ctt ttt cct gta tca ata cca atc acg gca 4485
Leu Val Ile Ser Gly Leu Phe Pro Val Ser Ile Pro Ile Thr Ala
1450 1455 1460
gca gca tgg tac ctg tgg gaa gtg aag aaa caa cgg gcc gga gta 4530
Ala Ala Trp Tyr Leu Trp Glu Val Lys Lys Gln Arg Ala Gly Val
1465 1470 1475
ttg tgg gat gtt cct tca ccc cca ccc atg gga aag gct gaa ctg 4575
Leu Trp Asp Val Pro Ser Pro Pro Pro Met Gly Lys Ala Glu Leu
1480 1485 1490
gaa gat gga gcc tat aga att aag caa aaa ggg att ctt gga tat 4620
Glu Asp Gly Ala Tyr Arg Ile Lys Gln Lys Gly Ile Leu Gly Tyr
1495 1500 1505
tcc cag atc gga gcc gga gtt tac aaa gaa gga aca ttc cat aca 4665
Ser Gln Ile Gly Ala Gly Val Tyr Lys Glu Gly Thr Phe His Thr
1510 1515 1520
atg tgg cat gtc aca cgt ggc gct gtt cta atg cat aaa gga aag 4710
Met Trp His Val Thr Arg Gly Ala Val Leu Met His Lys Gly Lys
1525 1530 1535
agg att gaa cca tca tgg gcg gac gtc aag aaa gac cta ata tca 4755
Arg Ile Glu Pro Ser Trp Ala Asp Val Lys Lys Asp Leu Ile Ser
1540 1545 1550
tat gga gga ggc tgg aag tta gaa gga gaa tgg aag gaa gga gaa 4800
Tyr Gly Gly Gly Trp Lys Leu Glu Gly Glu Trp Lys Glu Gly Glu
1555 1560 1565
gaa gtc cag gta ttg gca ctg gag cct gga aaa aat cca aga gcc 4845
Glu Val Gln Val Leu Ala Leu Glu Pro Gly Lys Asn Pro Arg Ala
1570 1575 1580
gtc caa acg aaa cct ggt ctt ttc aaa acc aac gcc gga aca ata 4890
Val Gln Thr Lys Pro Gly Leu Phe Lys Thr Asn Ala Gly Thr Ile
1585 1590 1595
ggt gct gta tct ctg gac ttt tct cct gga acg tca gga tct cca 4935
Gly Ala Val Ser Leu Asp Phe Ser Pro Gly Thr Ser Gly Ser Pro
1600 1605 1610
att atc gac aaa aaa gga aaa gtt gtg ggt ctt tat ggt aat ggt 4980
Ile Ile Asp Lys Lys Gly Lys Val Val Gly Leu Tyr Gly Asn Gly
1615 1620 1625
gtt gtt aca agg agt gga gca tat gtg agt gct ata gcc cag act 5025
Val Val Thr Arg Ser Gly Ala Tyr Val Ser Ala Ile Ala Gln Thr
1630 1635 1640
gaa aaa agc att gaa gac aac cca gag atc gaa gat gac att ttc 5070
Glu Lys Ser Ile Glu Asp Asn Pro Glu Ile Glu Asp Asp Ile Phe
1645 1650 1655
cga aag aga aga ctg acc atc atg gac ctc cac cca gga gcg gga 5115
Arg Lys Arg Arg Leu Thr Ile Met Asp Leu His Pro Gly Ala Gly
1660 1665 1670
aag acg aag aga tac ctt ccg gcc ata gtc aga gaa gct ata aaa 5160
Lys Thr Lys Arg Tyr Leu Pro Ala Ile Val Arg Glu Ala Ile Lys
1675 1680 1685
cgg ggt ttg aga aca tta atc ttg gcc ccc act aga gtt gtg gca 5205
Arg Gly Leu Arg Thr Leu Ile Leu Ala Pro Thr Arg Val Val Ala
1690 1695 1700
gct gaa atg gag gaa gcc ctt aga gga ctt cca ata aga tac cag 5250
Ala Glu Met Glu Glu Ala Leu Arg Gly Leu Pro Ile Arg Tyr Gln
1705 1710 1715
acc cca gcc atc aga gct gag cac acc ggg cgg gag att gtg gac 5295
Thr Pro Ala Ile Arg Ala Glu His Thr Gly Arg Glu Ile Val Asp
1720 1725 1730
cta atg tgt cat gcc aca ttt acc atg agg ctg cta tca cca gtt 5340
Leu Met Cys His Ala Thr Phe Thr Met Arg Leu Leu Ser Pro Val
1735 1740 1745
aga gtg cca aac tac aac ctg att atc atg gac gaa gcc cat ttc 5385
Arg Val Pro Asn Tyr Asn Leu Ile Ile Met Asp Glu Ala His Phe
1750 1755 1760
aca gac cca gca agt ata gca gct aga gga tac atc tca act cga 5430
Thr Asp Pro Ala Ser Ile Ala Ala Arg Gly Tyr Ile Ser Thr Arg
1765 1770 1775
gtg gag atg ggt gag gca gct ggg att ttt atg aca gcc act ccc 5475
Val Glu Met Gly Glu Ala Ala Gly Ile Phe Met Thr Ala Thr Pro
1780 1785 1790
ccg gga agc aga gac cca ttt cct cag agc aat gca cca atc ata 5520
Pro Gly Ser Arg Asp Pro Phe Pro Gln Ser Asn Ala Pro Ile Ile
1795 1800 1805
gat gaa gaa aga gaa atc cct gaa cgt tcg tgg aat tcc gga cat 5565
Asp Glu Glu Arg Glu Ile Pro Glu Arg Ser Trp Asn Ser Gly His
1810 1815 1820
gaa tgg gtc acg gat ttt aaa ggg aag act gtt tgg ttc gtt cca 5610
Glu Trp Val Thr Asp Phe Lys Gly Lys Thr Val Trp Phe Val Pro
1825 1830 1835
agt ata aaa gca gga aat gat ata gca gct tgc ctg agg aaa aat 5655
Ser Ile Lys Ala Gly Asn Asp Ile Ala Ala Cys Leu Arg Lys Asn
1840 1845 1850
gga aag aaa gtg ata caa ctc agt agg aag acc ttt gat tct gag 5700
Gly Lys Lys Val Ile Gln Leu Ser Arg Lys Thr Phe Asp Ser Glu
1855 1860 1865
tat gtc aag act aga acc aat gat tgg gac ttc gtg gtt aca act 5745
Tyr Val Lys Thr Arg Thr Asn Asp Trp Asp Phe Val Val Thr Thr
1870 1875 1880
gac att tca gaa atg ggt gcc aat ttc aag gct gag agg gtt ata 5790
Asp Ile Ser Glu Met Gly Ala Asn Phe Lys Ala Glu Arg Val Ile
1885 1890 1895
gac ccc aga cgc tgc atg aaa cca gtc ata cta aca gat ggt gaa 5835
Asp Pro Arg Arg Cys Met Lys Pro Val Ile Leu Thr Asp Gly Glu
1900 1905 1910
gag cgg gtg att ctg gca gga cct atg cca gtg acc cac tct agt 5880
Glu Arg Val Ile Leu Ala Gly Pro Met Pro Val Thr His Ser Ser
1915 1920 1925
gca gca caa aga aga ggg aga ata gga aga aat cca aaa aat gag 5925
Ala Ala Gln Arg Arg Gly Arg Ile Gly Arg Asn Pro Lys Asn Glu
1930 1935 1940
aat gac cag tac ata tac atg ggg gaa cct ctg gaa aat gat gaa 5970
Asn Asp Gln Tyr Ile Tyr Met Gly Glu Pro Leu Glu Asn Asp Glu
1945 1950 1955
gac tgt gca cac tgg aaa gaa gct aaa atg ctc cta gat aac atc 6015
Asp Cys Ala His Trp Lys Glu Ala Lys Met Leu Leu Asp Asn Ile
1960 1965 1970
aac acg cca gaa gga atc att cct agc atg ttc gaa cca gag cgt 6060
Asn Thr Pro Glu Gly Ile Ile Pro Ser Met Phe Glu Pro Glu Arg
1975 1980 1985
gaa aag gtg gat gcc att gat ggc gaa tac cgc ttg aga gga gaa 6105
Glu Lys Val Asp Ala Ile Asp Gly Glu Tyr Arg Leu Arg Gly Glu
1990 1995 2000
gca agg aaa acc ttt gta gac tta atg aga aga gga gac cta cca 6150
Ala Arg Lys Thr Phe Val Asp Leu Met Arg Arg Gly Asp Leu Pro
2005 2010 2015
gtc tgg ttg gcc tac aga gtg gca gct gaa ggc atc aac tac gca 6195
Val Trp Leu Ala Tyr Arg Val Ala Ala Glu Gly Ile Asn Tyr Ala
2020 2025 2030
gac aga agg tgg tgt ttt gat gga gtc aag aac aac caa atc cta 6240
Asp Arg Arg Trp Cys Phe Asp Gly Val Lys Asn Asn Gln Ile Leu
2035 2040 2045
gaa gaa aac gtg gaa gtt gaa atc tgg aca aaa gaa ggg gaa agg 6285
Glu Glu Asn Val Glu Val Glu Ile Trp Thr Lys Glu Gly Glu Arg
2050 2055 2060
aag aaa ttg aaa ccc aga tgg ttg gat gct agg atc tat tct gac 6330
Lys Lys Leu Lys Pro Arg Trp Leu Asp Ala Arg Ile Tyr Ser Asp
2065 2070 2075
cca ctg gcg cta aaa gaa ttt aag gaa ttt gca gcc gga aga aag 6375
Pro Leu Ala Leu Lys Glu Phe Lys Glu Phe Ala Ala Gly Arg Lys
2080 2085 2090
tct ctg acc ctg aac cta atc aca gaa atg ggt agg ctc cca acc 6420
Ser Leu Thr Leu Asn Leu Ile Thr Glu Met Gly Arg Leu Pro Thr
2095 2100 2105
ttc atg act cag aag gca aga gac gca ctg gac aac tta gca gtg 6465
Phe Met Thr Gln Lys Ala Arg Asp Ala Leu Asp Asn Leu Ala Val
2110 2115 2120
ctg cac acg gct gag gca ggt gga agg gcg tac aac cat gct ctc 6510
Leu His Thr Ala Glu Ala Gly Gly Arg Ala Tyr Asn His Ala Leu
2125 2130 2135
agt gaa ctg ccg gag acc ctg gag aca ttg ctt tta ctg aca ctt 6555
Ser Glu Leu Pro Glu Thr Leu Glu Thr Leu Leu Leu Leu Thr Leu
2140 2145 2150
ctg gct aca gtc acg gga ggg atc ttt tta ttc ttg atg agc gga 6600
Leu Ala Thr Val Thr Gly Gly Ile Phe Leu Phe Leu Met Ser Gly
2155 2160 2165
agg ggc ata ggg aag atg acc ctg gga atg tgc tgc ata atc acg 6645
Arg Gly Ile Gly Lys Met Thr Leu Gly Met Cys Cys Ile Ile Thr
2170 2175 2180
gct agc atc ctc cta tgg tac gca caa ata cag cca cac tgg ata 6690
Ala Ser Ile Leu Leu Trp Tyr Ala Gln Ile Gln Pro His Trp Ile
2185 2190 2195
gca gct tca ata ata ctg gag ttt ttt ctc ata gtt ttg ctt att 6735
Ala Ala Ser Ile Ile Leu Glu Phe Phe Leu Ile Val Leu Leu Ile
2200 2205 2210
cca gaa cct gaa aaa cag aga aca ccc caa gac aac caa ctg acc 6780
Pro Glu Pro Glu Lys Gln Arg Thr Pro Gln Asp Asn Gln Leu Thr
2215 2220 2225
tac gtt gtc ata gcc atc ctc aca gtg gtg gcc gca acc atg gca 6825
Tyr Val Val Ile Ala Ile Leu Thr Val Val Ala Ala Thr Met Ala
2230 2235 2240
aac gag atg ggt ttc cta gaa aaa acg aag aaa gat ctc gga ttg 6870
Asn Glu Met Gly Phe Leu Glu Lys Thr Lys Lys Asp Leu Gly Leu
2245 2250 2255
gga agc att gca acc cag caa ccc gag agc aac atc ctg gac ata 6915
Gly Ser Ile Ala Thr Gln Gln Pro Glu Ser Asn Ile Leu Asp Ile
2260 2265 2270
gat cta cgt cct gca tca gca tgg acg ctg tat gcc gtg gcc aca 6960
Asp Leu Arg Pro Ala Ser Ala Trp Thr Leu Tyr Ala Val Ala Thr
2275 2280 2285
aca ttt gtt aca cca atg ttg aga cat agc att gaa aat tcc tca 7005
Thr Phe Val Thr Pro Met Leu Arg His Ser Ile Glu Asn Ser Ser
2290 2295 2300
gtg aat gtg tcc cta aca gct ata gcc aac caa gcc aca gtg tta 7050
Val Asn Val Ser Leu Thr Ala Ile Ala Asn Gln Ala Thr Val Leu
2305 2310 2315
atg ggt ctc ggg aaa gga tgg cca ttg tca aag atg gac atc gga 7095
Met Gly Leu Gly Lys Gly Trp Pro Leu Ser Lys Met Asp Ile Gly
2320 2325 2330
gtt ccc ctt ctc gcc att gga tgc tac tca caa gtc aac ccc ata 7140
Val Pro Leu Leu Ala Ile Gly Cys Tyr Ser Gln Val Asn Pro Ile
2335 2340 2345
act ctc aca gca gct ctt ttc tta ttg gta gca cat tat gcc atc 7185
Thr Leu Thr Ala Ala Leu Phe Leu Leu Val Ala His Tyr Ala Ile
2350 2355 2360
ata ggg cca gga ctc caa gca aaa gca acc aga gaa gct cag aaa 7230
Ile Gly Pro Gly Leu Gln Ala Lys Ala Thr Arg Glu Ala Gln Lys
2365 2370 2375
aga gca gcg gcg ggc atc atg aaa aac cca act gtc gat gga ata 7275
Arg Ala Ala Ala Gly Ile Met Lys Asn Pro Thr Val Asp Gly Ile
2380 2385 2390
aca gtg att gac cta gat cca ata cct tat gat cca aag ttt gaa 7320
Thr Val Ile Asp Leu Asp Pro Ile Pro Tyr Asp Pro Lys Phe Glu
2395 2400 2405
aag cag ttg gga caa gta atg ctc cta gtc ctc tgc gtg act caa 7365
Lys Gln Leu Gly Gln Val Met Leu Leu Val Leu Cys Val Thr Gln
2410 2415 2420
gta ttg atg atg agg act aca tgg gct ctg tgt gag gct tta acc 7410
Val Leu Met Met Arg Thr Thr Trp Ala Leu Cys Glu Ala Leu Thr
2425 2430 2435
tta gct acc ggg ccc atc tcc aca ttg tgg gaa gga aat cca ggg 7455
Leu Ala Thr Gly Pro Ile Ser Thr Leu Trp Glu Gly Asn Pro Gly
2440 2445 2450
agg ttt tgg aac act acc att gcg gtg tca atg gct aac att ttt 7500
Arg Phe Trp Asn Thr Thr Ile Ala Val Ser Met Ala Asn Ile Phe
2455 2460 2465
aga ggg agt tac ttg gcc gga gct gga ctt ctc ttt tct att atg 7545
Arg Gly Ser Tyr Leu Ala Gly Ala Gly Leu Leu Phe Ser Ile Met
2470 2475 2480
aag aac aca acc aac aca aga agg gga act ggc aac ata gga gag 7590
Lys Asn Thr Thr Asn Thr Arg Arg Gly Thr Gly Asn Ile Gly Glu
2485 2490 2495
acg ctt gga gag aaa tgg aaa agc cga ttg aac gca ttg gga aaa 7635
Thr Leu Gly Glu Lys Trp Lys Ser Arg Leu Asn Ala Leu Gly Lys
2500 2505 2510
agt gaa ttc cag atc tac aag aaa agt gga atc cag gaa gtg gat 7680
Ser Glu Phe Gln Ile Tyr Lys Lys Ser Gly Ile Gln Glu Val Asp
2515 2520 2525
aga acc tta gca aaa gaa ggc att aaa aga gga gaa acg gac cat 7725
Arg Thr Leu Ala Lys Glu Gly Ile Lys Arg Gly Glu Thr Asp His
2530 2535 2540
cac gct gtg tcg cga ggc tca gca aaa ctg aga tgg ttc gtt gag 7770
His Ala Val Ser Arg Gly Ser Ala Lys Leu Arg Trp Phe Val Glu
2545 2550 2555
aga aac atg gtc aca cca gaa ggg aaa gta gtg gac ctc ggt tgt 7815
Arg Asn Met Val Thr Pro Glu Gly Lys Val Val Asp Leu Gly Cys
2560 2565 2570
ggc aga gga ggc tgg tca tac tat tgt gga gga cta aag aat gta 7860
Gly Arg Gly Gly Trp Ser Tyr Tyr Cys Gly Gly Leu Lys Asn Val
2575 2580 2585
aga gaa gtc aaa ggc cta aca aaa gga gga cca gga cac gaa gaa 7905
Arg Glu Val Lys Gly Leu Thr Lys Gly Gly Pro Gly His Glu Glu
2590 2595 2600
ccc atc ccc atg tca aca tat ggg tgg aat cta gtg cgt ctt caa 7950
Pro Ile Pro Met Ser Thr Tyr Gly Trp Asn Leu Val Arg Leu Gln
2605 2610 2615
agt gga gtt gac gtt ttc ttc atc ccg cca gaa aag tgt gac aca 7995
Ser Gly Val Asp Val Phe Phe Ile Pro Pro Glu Lys Cys Asp Thr
2620 2625 2630
tta ttg tgt gac ata ggg gag tca tca cca aat ccc aca gtg gaa 8040
Leu Leu Cys Asp Ile Gly Glu Ser Ser Pro Asn Pro Thr Val Glu
2635 2640 2645
gca gga cga aca ctc aga gtc ctt aac tta gta gaa aat tgg ttg 8085
Ala Gly Arg Thr Leu Arg Val Leu Asn Leu Val Glu Asn Trp Leu
2650 2655 2660
aac aac aac act caa ttt tgc ata aag gtt ctc aac cca tat atg 8130
Asn Asn Asn Thr Gln Phe Cys Ile Lys Val Leu Asn Pro Tyr Met
2665 2670 2675
ccc tca gtc ata gaa aaa atg gaa gca cta caa agg aaa tat gga 8175
Pro Ser Val Ile Glu Lys Met Glu Ala Leu Gln Arg Lys Tyr Gly
2680 2685 2690
gga gcc tta gtg agg aat cca ctc tca cga aac tcc aca cat gag 8220
Gly Ala Leu Val Arg Asn Pro Leu Ser Arg Asn Ser Thr His Glu
2695 2700 2705
atg tac tgg gta tcc aat gct tcc ggg aac ata gtg tca tca gtg 8265
Met Tyr Trp Val Ser Asn Ala Ser Gly Asn Ile Val Ser Ser Val
2710 2715 2720
aac atg att tca agg atg ttg atc aac aga ttt aca atg aga tac 8310
Asn Met Ile Ser Arg Met Leu Ile Asn Arg Phe Thr Met Arg Tyr
2725 2730 2735
aag aaa gcc act tac gag ccg gat gtt gac ctc gga agc gga acc 8355
Lys Lys Ala Thr Tyr Glu Pro Asp Val Asp Leu Gly Ser Gly Thr
2740 2745 2750
cgt aac atc ggg att gaa agt gag ata cca aac cta gat ata att 8400
Arg Asn Ile Gly Ile Glu Ser Glu Ile Pro Asn Leu Asp Ile Ile
2755 2760 2765
ggg aaa aga ata gaa aaa ata aag caa gag cat gaa aca tca tgg 8445
Gly Lys Arg Ile Glu Lys Ile Lys Gln Glu His Glu Thr Ser Trp
2770 2775 2780
cac tat gac caa gac cac cca tac aaa acg tgg gca tac cat ggt 8490
His Tyr Asp Gln Asp His Pro Tyr Lys Thr Trp Ala Tyr His Gly
2785 2790 2795
agc tat gaa aca aaa cag act gga tca gca tca tcc atg gtc aac 8535
Ser Tyr Glu Thr Lys Gln Thr Gly Ser Ala Ser Ser Met Val Asn
2800 2805 2810
gga gtg gtc agg ctg ctg aca aaa cct tgg gac gtc gtc ccc atg 8580
Gly Val Val Arg Leu Leu Thr Lys Pro Trp Asp Val Val Pro Met
2815 2820 2825
gtg aca cag atg gca atg aca gac acg act cca ttt gga caa cag 8625
Val Thr Gln Met Ala Met Thr Asp Thr Thr Pro Phe Gly Gln Gln
2830 2835 2840
cgc gtt ttt aaa gag aaa gtg gac acg aga acc caa gaa ccg aaa 8670
Arg Val Phe Lys Glu Lys Val Asp Thr Arg Thr Gln Glu Pro Lys
2845 2850 2855
gaa ggc acg aag aaa cta atg aaa ata aca gca gag tgg ctt tgg 8715
Glu Gly Thr Lys Lys Leu Met Lys Ile Thr Ala Glu Trp Leu Trp
2860 2865 2870
aaa gaa tta ggg aag aaa aag aca ccc agg atg tgc acc aga gaa 8760
Lys Glu Leu Gly Lys Lys Lys Thr Pro Arg Met Cys Thr Arg Glu
2875 2880 2885
gaa ttc aca aga aag gtg aga agc aat gca gcc ttg ggg gcc ata 8805
Glu Phe Thr Arg Lys Val Arg Ser Asn Ala Ala Leu Gly Ala Ile
2890 2895 2900
ttc act gat gag aac aag tgg aag tcg gca cgt gag gct gtt gaa 8850
Phe Thr Asp Glu Asn Lys Trp Lys Ser Ala Arg Glu Ala Val Glu
2905 2910 2915
gat agt agg ttt tgg gag ctg gtt gac aag gaa agg aat ctc cat 8895
Asp Ser Arg Phe Trp Glu Leu Val Asp Lys Glu Arg Asn Leu His
2920 2925 2930
ctt gaa gga aag tgt gaa aca tgt gtg tac aac atg atg gga aaa 8940
Leu Glu Gly Lys Cys Glu Thr Cys Val Tyr Asn Met Met Gly Lys
2935 2940 2945
aga gag aag aag cta ggg gaa ttc ggc aag gca aaa ggc agc aga 8985
Arg Glu Lys Lys Leu Gly Glu Phe Gly Lys Ala Lys Gly Ser Arg
2950 2955 2960
gcc ata tgg tac atg tgg ctt gga gca cgc ttc tta gag ttt gaa 9030
Ala Ile Trp Tyr Met Trp Leu Gly Ala Arg Phe Leu Glu Phe Glu
2965 2970 2975
gcc cta gga ttc tta aat gaa gat cac tgg ttc tcc aga gag aac 9075
Ala Leu Gly Phe Leu Asn Glu Asp His Trp Phe Ser Arg Glu Asn
2980 2985 2990
tcc ctg agt gga gtg gaa gga gaa ggg ctg cac aag cta ggt tac 9120
Ser Leu Ser Gly Val Glu Gly Glu Gly Leu His Lys Leu Gly Tyr
2995 3000 3005
att cta aga gac gtg agc aag aaa gag gga gga gca atg tat gcc 9165
Ile Leu Arg Asp Val Ser Lys Lys Glu Gly Gly Ala Met Tyr Ala
3010 3015 3020
gat gac acc gca gga tgg gat aca aga atc aca cta gaa gac cta 9210
Asp Asp Thr Ala Gly Trp Asp Thr Arg Ile Thr Leu Glu Asp Leu
3025 3030 3035
aaa aat gaa gaa atg gta aca aac cac atg gaa gga gaa cac aag 9255
Lys Asn Glu Glu Met Val Thr Asn His Met Glu Gly Glu His Lys
3040 3045 3050
aaa cta gcc gag gcc att ttc aaa cta acg tac caa aac aag gtg 9300
Lys Leu Ala Glu Ala Ile Phe Lys Leu Thr Tyr Gln Asn Lys Val
3055 3060 3065
gtg cgt gtg caa aga cca aca cca aga ggc aca gta atg gac atc 9345
Val Arg Val Gln Arg Pro Thr Pro Arg Gly Thr Val Met Asp Ile
3070 3075 3080
ata tcg aga aga gac caa aga ggt agt gga caa gtt ggc acc tat 9390
Ile Ser Arg Arg Asp Gln Arg Gly Ser Gly Gln Val Gly Thr Tyr
3085 3090 3095
gga ctc aat act ttc acc aat atg gaa gcc caa cta atc aga cag 9435
Gly Leu Asn Thr Phe Thr Asn Met Glu Ala Gln Leu Ile Arg Gln
3100 3105 3110
atg gag gga gaa gga gtc ttt aaa agc att cag cac cta aca atc 9480
Met Glu Gly Glu Gly Val Phe Lys Ser Ile Gln His Leu Thr Ile
3115 3120 3125
aca gaa gaa atc gct gtg caa aac tgg tta gca aga gtg ggg cgc 9525
Thr Glu Glu Ile Ala Val Gln Asn Trp Leu Ala Arg Val Gly Arg
3130 3135 3140
gaa agg tta tca aga atg gcc atc agt gga gat gat tgt gtt gtg 9570
Glu Arg Leu Ser Arg Met Ala Ile Ser Gly Asp Asp Cys Val Val
3145 3150 3155
aaa cct tta gat gac agg ttc gca agc gct tta aca gct cta aat 9615
Lys Pro Leu Asp Asp Arg Phe Ala Ser Ala Leu Thr Ala Leu Asn
3160 3165 3170
gac atg gga aag att agg aaa gac ata caa caa tgg gaa cct tca 9660
Asp Met Gly Lys Ile Arg Lys Asp Ile Gln Gln Trp Glu Pro Ser
3175 3180 3185
aga gga tgg aat gat tgg aca caa gtg ccc ttc tgt tca cac cat 9705
Arg Gly Trp Asn Asp Trp Thr Gln Val Pro Phe Cys Ser His His
3190 3195 3200
ttc cat gag tta atc atg aaa gac ggt cgc gta ctc gtt gtt cca 9750
Phe His Glu Leu Ile Met Lys Asp Gly Arg Val Leu Val Val Pro
3205 3210 3215
tgt aga aac caa gat gaa ctg att ggc aga gcc cga atc tcc caa 9795
Cys Arg Asn Gln Asp Glu Leu Ile Gly Arg Ala Arg Ile Ser Gln
3220 3225 3230
gga gca ggg tgg tct ttg cgg gag acg gcc tgt ttg ggg aag tct 9840
Gly Ala Gly Trp Ser Leu Arg Glu Thr Ala Cys Leu Gly Lys Ser
3235 3240 3245
tac gcc caa atg tgg agc ttg atg tac ttc cac aga cgc gac ctc 9885
Tyr Ala Gln Met Trp Ser Leu Met Tyr Phe His Arg Arg Asp Leu
3250 3255 3260
agg ctg gcg gca aat gct att tgc tcg gca gta cca tca cat tgg 9930
Arg Leu Ala Ala Asn Ala Ile Cys Ser Ala Val Pro Ser His Trp
3265 3270 3275
gtt cca aca agt cga aca acc tgg tcc ata cat gct aaa cat gaa 9975
Val Pro Thr Ser Arg Thr Thr Trp Ser Ile His Ala Lys His Glu
3280 3285 3290
tgg atg aca acg gaa gac atg ctg aca gtc tgg aac agg gtg tgg 10020
Trp Met Thr Thr Glu Asp Met Leu Thr Val Trp Asn Arg Val Trp
3295 3300 3305
att caa gaa aac cca tgg atg gaa gac aaa act cca gtg gaa tca 10065
Ile Gln Glu Asn Pro Trp Met Glu Asp Lys Thr Pro Val Glu Ser
3310 3315 3320
tgg gag gaa atc cca tac ttg ggg aaa aga gaa gac caa tgg tgc 10110
Trp Glu Glu Ile Pro Tyr Leu Gly Lys Arg Glu Asp Gln Trp Cys
3325 3330 3335
ggc tca ttg att ggg tta aca agc agg gcc acc tgg gca aag aac 10155
Gly Ser Leu Ile Gly Leu Thr Ser Arg Ala Thr Trp Ala Lys Asn
3340 3345 3350
atc caa gca gca ata aat caa gtt aga tcc ctt ata ggc aat gaa 10200
Ile Gln Ala Ala Ile Asn Gln Val Arg Ser Leu Ile Gly Asn Glu
3355 3360 3365
gaa tac aca gat tac atg cca tcc atg aaa aga ttc aga aga gaa 10245
Glu Tyr Thr Asp Tyr Met Pro Ser Met Lys Arg Phe Arg Arg Glu
3370 3375 3380
gag gaa gaa gca gga gtt ctg tgg tag aaagcaaaac taacatgaaa 10292
Glu Glu Glu Ala Gly Val Leu Trp
3385 3390
caaggctaga agtcaggtcg gattaagcca tagtacggaa aaaactatgc tacctgtgag10352
ccccgtccaa ggacgttaaa agaagtcagg ccatcataaa tgccatagct tgagtaaact10412
atgcagcctg tagctccacc tgagaaggtg taaaaaatcc gggaggccac aaaccatgga10472
agctgtacgc atggcgtagt ggactagcgg ttagaggaga cccctccctt acaaatcgca10532
gcaacaatgg gggcccaagg cgagatgaag ctgtagtctc gctggaagga ctagaggtta10592
gaggagaccc ccccgaaaca aaaaacagca tattgacgct gggaaagacc agagatcctg10652
ctgtctcctc agcatcattc caggcacaga acgccagaaa atggaatggt gctgttgaat10712
caacaggttc t 10723
<210> 6
<211> 3391
<212> PRT
<213> 2型登革病毒
<400> 6
Met Asn Asn Gln Arg Lys Lys Ala Lys Asn Thr Pro Phe Asn Met Leu
1 5 10 15
Lys Arg Glu Arg Asn Arg Val Ser Thr Val Gln Gln Leu Thr Lys Arg
20 25 30
Phe Ser Leu Gly Met Leu Gln Gly Arg Gly Pro Leu Lys Leu Phe Met
35 40 45
Ala Leu Val Ala Phe Leu Arg Phe Leu Thr Ile Pro Pro Thr Ala Gly
50 55 60
Ile Leu Lys Arg Trp Gly Thr Ile Lys Lys Ser Lys Ala Ile Asn Val
65 70 75 80
Leu Arg Gly Phe Arg Lys Glu Ile Gly Arg Met Leu Asn Ile Leu Asn
85 90 95
Arg Arg Arg Arg Ser Ala Gly Met Ile Ile Met Leu Ile Pro Thr Val
100 105 110
Met Ala Phe His Leu Thr Thr Arg Asn Gly Glu Pro His Met Ile Val
115 120 125
Ser Arg Gln Glu Lys Gly Lys Ser Leu Leu Phe Lys Thr Glu Asp Gly
130 135 140
Val Asn Met Cys Thr Leu Met Ala Met Asp Leu Gly Glu Leu Cys Glu
145 150 155 160
Asp Thr Ile Thr Tyr Lys Cys Pro Leu Leu Arg Gln Asn Glu Pro Glu
165 170 175
Asp Ile Asp Cys Trp Cys Asn Ser Thr Ser Thr Trp Val Thr Tyr Gly
180 185 190
Thr Cys Thr Thr Met Gly Glu His Arg Arg Glu Lys Arg Ser Val Ala
195 200 205
Leu Val Pro His Val Gly Met Gly Leu Glu Thr Arg Thr Glu Thr Trp
210 215 220
Met Ser Ser Glu Gly Ala Trp Lys His Val Gln Arg Ile Glu Thr Trp
225 230 235 240
Ile Leu Arg His Pro Gly Phe Thr Met Met Ala Ala Ile Leu Ala Tyr
245 250 255
Thr Ile Gly Thr Thr His Phe Gln Arg Ala Leu Ile Phe Ile Leu Leu
260 265 270
Thr Ala Val Thr Pro Ser Met Thr Met Arg Cys Ile Gly Met Ser Asn
275 280 285
Arg Asp Phe Val Glu Gly Val Ser Gly Gly Ser Trp Val Asp Ile Val
290 295 300
Leu Glu His Gly Ser Cys Val Thr Thr Met Ala Lys Asn Lys Pro Thr
305 310 315 320
Leu Asp Phe Glu Leu Ile Lys Thr Glu Ala Lys Gln Pro Ala Thr Leu
325 330 335
Arg Lys Tyr Cys Ile Glu Ala Lys Leu Thr Asn Thr Thr Thr Glu Ser
340 345 350
Arg Cys Pro Thr Gln Gly Glu Pro Ser Leu Asn Glu Glu Gln Asp Lys
355 360 365
Arg Phe Val Cys Lys His Ser Met Val Asp Arg Gly Trp Gly Asn Gly
370 375 380
Cys Gly Leu Phe Gly Lys Gly Gly Ile Val Thr Cys Ala Met Phe Arg
385 390 395 400
Cys Lys Lys Asn Met Glu Gly Lys Val Val Gln Pro Glu Asn Leu Glu
405 410 415
Tyr Thr Ile Val Ile Thr Pro His Ser Gly Glu Glu His Ala Val Gly
420 425 430
Asn Asp Thr Gly Lys His Gly Lys Glu Ile Lys Ile Thr Pro Gln Ser
435 440 445
Ser Ile Thr Glu Ala Glu Leu Thr Gly Tyr Gly Thr Val Thr Met Glu
450 455 460
Cys Ser Pro Arg Thr Gly Leu Asp Phe Asn Glu Met Val Leu Leu Gln
465 470 475 480
Met Glu Asn Lys Ala Trp Leu Val His Arg Gln Trp Phe Leu Asp Leu
485 490 495
Pro Leu Pro Trp Leu Pro Gly Ala Asp Thr Gln Gly Ser Asn Trp Ile
500 505 510
Gln Lys Glu Thr Leu Val Thr Phe Lys Asn Pro His Ala Lys Lys Gln
515 520 525
Asp Val Val Val Leu Gly Ser Gln Glu Gly Ala Met His Thr Ala Leu
530 535 540
Thr Gly Ala Thr Glu Ile Gln Met Ser Ser Gly Asn Leu Leu Phe Thr
545 550 555 560
Gly His Leu Lys Cys Arg Leu Arg Met Asp Lys Leu Gln Leu Lys Gly
565 570 575
Met Ser Tyr Ser Met Cys Thr Gly Lys Phe Lys Val Val Lys Glu Ile
580 585 590
Ala Glu Thr Gln His Gly Thr Ile Val Ile Arg Val Gln Tyr Glu Gly
595 600 605
Asp Gly Ser Pro Cys Lys Ile Pro Phe Glu Ile Met Asp Leu Glu Lys
610 615 620
Arg His Val Leu Gly Arg Leu Ile Thr Val Asn Pro Ile Val Thr Glu
625 630 635 640
Lys Asp Ser Pro Val Asn Ile Glu Ala Glu Pro Pro Phe Gly Asp Ser
645 650 655
Tyr Ile Ile Ile Gly Val Glu Pro Gly Gln Leu Lys Leu Asn Trp Phe
660 665 670
Lys Lys Gly Ser Ser Ile Gly Gln Met Phe Glu Thr Thr Met Arg Gly
675 680 685
Ala Lys Arg Met Ala Ile Leu Gly Asp Thr Ala Trp Asp Phe Gly Ser
690 695 700
Leu Gly Gly Val Phe Thr Ser Ile Gly Lys Ala Leu His Gln Val Phe
705 710 715 720
Gly Ala Ile Tyr Gly Ala Ala Phe Ser Gly Val Ser Trp Thr Met Lys
725 730 735
Ile Leu Ile Gly Val Ile Ile Thr Trp Ile Gly Met Asn Ser Arg Ser
740 745 750
Thr Ser Leu Ser Val Thr Leu Val Leu Val Gly Ile Val Thr Leu Tyr
755 760 765
Leu Gly Val Met Val Gln Ala Asp Ser Gly Cys Val Val Ser Trp Lys
770 775 780
Asn Lys Glu Leu Lys Cys Gly Ser Gly Ile Phe Ile Thr Asp Asn Val
785 790 795 800
His Thr Trp Thr Glu Gln Tyr Lys Phe Gln Pro Glu Ser Pro Ser Lys
805 810 815
Leu Ala Ser Ala Ile Gln Lys Ala His Glu Glu Gly Ile Cys Gly Ile
820 825 830
Arg Ser Val Thr Arg Leu Glu Asn Leu Met Trp Lys Gln Ile Thr Pro
835 840 845
Glu Leu Asn His Ile Leu Ser Glu Asn Glu Val Lys Leu Thr Ile Met
850 855 860
Thr Gly Asp Ile Lys Gly Ile Met Gln Ala Gly Lys Arg Ser Leu Arg
865 870 875 880
Pro Gln Pro Thr Glu Leu Lys Tyr Ser Trp Lys Thr Trp Gly Lys Ala
885 890 895
Lys Met Leu Ser Thr Glu Ser His Asn Gln Thr Phe Leu Ile Asp Gly
900 905 910
Pro Glu Thr Ala Glu Cys Pro Asn Thr Asn Arg Ala Trp Asn Ser Leu
915 920 925
Glu Val Glu Asp Tyr Gly Phe Gly Val Phe Thr Thr Asn Ile Trp Leu
930 935 940
Lys Leu Lys Glu Lys Gln Asp Val Phe Cys Asp Ser Lys Leu Met Ser
945 950 955 960
Ala Ala Ile Lys Asp Asn Arg Ala Val His Ala Asp Met Gly Tyr Trp
965 970 975
Ile Glu Ser Ala Leu Asn Asp Thr Trp Lys Ile Glu Lys Ala Ser Phe
980 985 990
Ile Glu Val Lys Asn Cys His Trp Pro Lys Ser His Thr Leu Trp Ser
995 1000 1005
Asn Gly Val Leu Glu Ser Glu Met Ile Ile Pro Lys Asn Leu Ala
1010 1015 1020
Gly Pro Val Ser Gln His Asn Tyr Arg Pro Gly Tyr His Thr Gln
1025 1030 1035
Ile Thr Gly Pro Trp His Leu Gly Lys Leu Glu Met Asp Phe Asp
1040 1045 1050
Phe Cys Asp Gly Thr Thr Val Val Val Thr Glu Asp Cys Gly Asn
1055 1060 1065
Arg Gly Pro Ser Leu Arg Thr Thr Thr Ala Ser Gly Lys Leu Ile
1070 1075 1080
Thr Glu Trp Cys Cys Arg Ser Cys Thr Leu Pro Pro Leu Arg Tyr
1085 1090 1095
Arg Gly Glu Asp Gly Cys Trp Tyr Gly Met Glu Ile Arg Pro Leu
1100 1105 1110
Lys Glu Lys Glu Glu Asn Leu Val Asn Ser Leu Val Thr Ala Gly
1115 1120 1125
His Gly Gln Val Asp Asn Phe Ser Leu Gly Val Leu Gly Met Ala
1130 1135 1140
Leu Phe Leu Glu Glu Met Leu Arg Thr Arg Val Gly Thr Lys His
1145 1150 1155
Ala Ile Leu Leu Val Ala Val Ser Phe Val Thr Leu Ile Thr Gly
1160 1165 1170
Asn Met Ser Phe Arg Asp Leu Gly Arg Val Met Val Met Val Gly
1175 1180 1185
Ala Thr Met Thr Asp Asp Ile Gly Met Gly Val Thr Tyr Leu Ala
1190 1195 1200
Leu Leu Ala Ala Phe Lys Val Arg Pro Thr Phe Ala Ala Gly Leu
1205 1210 1215
Leu Leu Arg Lys Leu Thr Ser Lys Glu Leu Met Met Thr Thr Ile
1220 1225 1230
Gly Ile Val Leu Leu Ser Gln Ser Thr Ile Pro Glu Thr Ile Leu
1235 1240 1245
Glu Leu Thr Asp Ala Leu Ala Leu Gly Met Met Val Leu Lys Met
1250 1255 1260
Val Arg Asn Met Glu Lys Tyr Gln Leu Ala Val Thr Ile Met Ala
1265 1270 1275
Ile Leu Cys Val Pro Asn Ala Val Ile Leu Gln Asn Ala Trp Lys
1280 1285 1290
Val Ser Cys Thr Ile Leu Ala Val Val Ser Val Ser Pro Leu Leu
1295 1300 1305
Leu Thr Ser Ser Gln Gln Lys Thr Asp Trp Ile Pro Leu Ala Leu
1310 1315 1320
Thr Ile Lys Gly Leu Asn Pro Thr Ala Ile Phe Leu Thr Thr Leu
1325 1330 1335
Ser Arg Thr Ser Lys Lys Arg Ser Trp Pro Leu Asn Glu Ala Ile
1340 1345 1350
Met Ala Val Gly Met Val Ser Ile Leu Ala Ser Ser Leu Leu Lys
1355 1360 1365
Asn Asp Ile Pro Met Thr Gly Pro Leu Val Ala Gly Gly Leu Leu
1370 1375 1380
Thr Val Cys Tyr Val Leu Thr Gly Arg Ser Ala Asp Leu Glu Leu
1385 1390 1395
Glu Arg Ala Ala Asp Val Lys Trp Glu Asp Gln Ala Glu Ile Ser
1400 1405 1410
Gly Ser Ser Pro Ile Leu Ser Ile Thr Ile Ser Glu Asp Gly Ser
1415 1420 1425
Met Ser Ile Lys Asn Glu Glu Glu Glu Gln Thr Leu Thr Ile Leu
1430 1435 1440
Ile Arg Thr Gly Leu Leu Val Ile Ser Gly Leu Phe Pro Val Ser
1445 1450 1455
Ile Pro Ile Thr Ala Ala Ala Trp Tyr Leu Trp Glu Val Lys Lys
1460 1465 1470
Gln Arg Ala Gly Val Leu Trp Asp Val Pro Ser Pro Pro Pro Met
1475 1480 1485
Gly Lys Ala Glu Leu Glu Asp Gly Ala Tyr Arg Ile Lys Gln Lys
1490 1495 1500
Gly Ile Leu Gly Tyr Ser Gln Ile Gly Ala Gly Val Tyr Lys Glu
1505 1510 1515
Gly Thr Phe His Thr Met Trp His Val Thr Arg Gly Ala Val Leu
1520 1525 1530
Met His Lys Gly Lys Arg Ile Glu Pro Ser Trp Ala Asp Val Lys
1535 1540 1545
Lys Asp Leu Ile Ser Tyr Gly Gly Gly Trp Lys Leu Glu Gly Glu
1550 1555 1560
Trp Lys Glu Gly Glu Glu Val Gln Val Leu Ala Leu Glu Pro Gly
1565 1570 1575
Lys Asn Pro Arg Ala Val Gln Thr Lys Pro Gly Leu Phe Lys Thr
1580 1585 1590
Asn Ala Gly Thr Ile Gly Ala Val Ser Leu Asp Phe Ser Pro Gly
1595 1600 1605
Thr Ser Gly Ser Pro Ile Ile Asp Lys Lys Gly Lys Val Val Gly
1610 1615 1620
Leu Tyr Gly Asn Gly Val Val Thr Arg Ser Gly Ala Tyr Val Ser
1625 1630 1635
Ala Ile Ala Gln Thr Glu Lys Ser Ile Glu Asp Asn Pro Glu Ile
1640 1645 1650
Glu Asp Asp Ile Phe Arg Lys Arg Arg Leu Thr Ile Met Asp Leu
1655 1660 1665
His Pro Gly Ala Gly Lys Thr Lys Arg Tyr Leu Pro Ala Ile Val
1670 1675 1680
Arg Glu Ala Ile Lys Arg Gly Leu Arg Thr Leu Ile Leu Ala Pro
1685 1690 1695
Thr Arg Val Val Ala Ala Glu Met Glu Glu Ala Leu Arg Gly Leu
1700 1705 1710
Pro Ile Arg Tyr Gln Thr Pro Ala Ile Arg Ala Glu His Thr Gly
1715 1720 1725
Arg Glu Ile Val Asp Leu Met Cys His Ala Thr Phe Thr Met Arg
1730 1735 1740
Leu Leu Ser Pro Val Arg Val Pro Asn Tyr Asn Leu Ile Ile Met
1745 1750 1755
Asp Glu Ala His Phe Thr Asp Pro Ala Ser Ile Ala Ala Arg Gly
1760 1765 1770
Tyr Ile Ser Thr Arg Val Glu Met Gly Glu Ala Ala Gly Ile Phe
1775 1780 1785
Met Thr Ala Thr Pro Pro Gly Ser Arg Asp Pro Phe Pro Gln Ser
1790 1795 1800
Asn Ala Pro Ile Ile Asp Glu Glu Arg Glu Ile Pro Glu Arg Ser
1805 1810 1815
Trp Asn Ser Gly His Glu Trp Val Thr Asp Phe Lys Gly Lys Thr
1820 1825 1830
Val Trp Phe Val Pro Ser Ile Lys Ala Gly Asn Asp Ile Ala Ala
1835 1840 1845
Cys Leu Arg Lys Asn Gly Lys Lys Val Ile Gln Leu Ser Arg Lys
1850 1855 1860
Thr Phe Asp Ser Glu Tyr Val Lys Thr Arg Thr Asn Asp Trp Asp
1865 1870 1875
Phe Val Val Thr Thr Asp Ile Ser Glu Met Gly Ala Asn Phe Lys
1880 1885 1890
Ala Glu Arg Val Ile Asp Pro Arg Arg Cys Met Lys Pro Val Ile
1895 1900 1905
Leu Thr Asp Gly Glu Glu Arg Val Ile Leu Ala Gly Pro Met Pro
1910 1915 1920
Val Thr His Ser Ser Ala Ala Gln Arg Arg Gly Arg Ile Gly Arg
1925 1930 1935
Asn Pro Lys Asn Glu Asn Asp Gln Tyr Ile Tyr Met Gly Glu Pro
1940 1945 1950
Leu Glu Asn Asp Glu Asp Cys Ala His Trp Lys Glu Ala Lys Met
1955 1960 1965
Leu Leu Asp Asn Ile Asn Thr Pro Glu Gly Ile Ile Pro Ser Met
1970 1975 1980
Phe Glu Pro Glu Arg Glu Lys Val Asp Ala Ile Asp Gly Glu Tyr
1985 1990 1995
Arg Leu Arg Gly Glu Ala Arg Lys Thr Phe Val Asp Leu Met Arg
2000 2005 2010
Arg Gly Asp Leu Pro Val Trp Leu Ala Tyr Arg Val Ala Ala Glu
2015 2020 2025
Gly Ile Asn Tyr Ala Asp Arg Arg Trp Cys Phe Asp Gly Val Lys
2030 2035 2040
Asn Asn Gln Ile Leu Glu Glu Asn Val Glu Val Glu Ile Trp Thr
2045 2050 2055
Lys Glu Gly Glu Arg Lys Lys Leu Lys Pro Arg Trp Leu Asp Ala
2060 2065 2070
Arg Ile Tyr Ser Asp Pro Leu Ala Leu Lys Glu Phe Lys Glu Phe
2075 2080 2085
Ala Ala Gly Arg Lys Ser Leu Thr Leu Asn Leu Ile Thr Glu Met
2090 2095 2100
Gly Arg Leu Pro Thr Phe Met Thr Gln Lys Ala Arg Asp Ala Leu
2105 2110 2115
Asp Asn Leu Ala Val Leu His Thr Ala Glu Ala Gly Gly Arg Ala
2120 2125 2130
Tyr Asn His Ala Leu Ser Glu Leu Pro Glu Thr Leu Glu Thr Leu
2135 2140 2145
Leu Leu Leu Thr Leu Leu Ala Thr Val Thr Gly Gly Ile Phe Leu
2150 2155 2160
Phe Leu Met Ser Gly Arg Gly Ile Gly Lys Met Thr Leu Gly Met
2165 2170 2175
Cys Cys Ile Ile Thr Ala Ser Ile Leu Leu Trp Tyr Ala Gln Ile
2180 2185 2190
Gln Pro His Trp Ile Ala Ala Ser Ile Ile Leu Glu Phe Phe Leu
2195 2200 2205
Ile Val Leu Leu Ile Pro Glu Pro Glu Lys Gln Arg Thr Pro Gln
2210 2215 2220
Asp Asn Gln Leu Thr Tyr Val Val Ile Ala Ile Leu Thr Val Val
2225 2230 2235
Ala Ala Thr Met Ala Asn Glu Met Gly Phe Leu Glu Lys Thr Lys
2240 2245 2250
Lys Asp Leu Gly Leu Gly Ser Ile Ala Thr Gln Gln Pro Glu Ser
2255 2260 2265
Asn Ile Leu Asp Ile Asp Leu Arg Pro Ala Ser Ala Trp Thr Leu
2270 2275 2280
Tyr Ala Val Ala Thr Thr Phe Val Thr Pro Met Leu Arg His Ser
2285 2290 2295
Ile Glu Asn Ser Ser Val Asn Val Ser Leu Thr Ala Ile Ala Asn
2300 2305 2310
Gln Ala Thr Val Leu Met Gly Leu Gly Lys Gly Trp Pro Leu Ser
2315 2320 2325
Lys Met Asp Ile Gly Val Pro Leu Leu Ala Ile Gly Cys Tyr Ser
2330 2335 2340
Gln Val Asn Pro Ile Thr Leu Thr Ala Ala Leu Phe Leu Leu Val
2345 2350 2355
Ala His Tyr Ala Ile Ile Gly Pro Gly Leu Gln Ala Lys Ala Thr
2360 2365 2370
Arg Glu Ala Gln Lys Arg Ala Ala Ala Gly Ile Met Lys Asn Pro
2375 2380 2385
Thr Val Asp Gly Ile Thr Val Ile Asp Leu Asp Pro Ile Pro Tyr
2390 2395 2400
Asp Pro Lys Phe Glu Lys Gln Leu Gly Gln Val Met Leu Leu Val
2405 2410 2415
Leu Cys Val Thr Gln Val Leu Met Met Arg Thr Thr Trp Ala Leu
2420 2425 2430
Cys Glu Ala Leu Thr Leu Ala Thr Gly Pro Ile Ser Thr Leu Trp
2435 2440 2445
Glu Gly Asn Pro Gly Arg Phe Trp Asn Thr Thr Ile Ala Val Ser
2450 2455 2460
Met Ala Asn Ile Phe Arg Gly Ser Tyr Leu Ala Gly Ala Gly Leu
2465 2470 2475
Leu Phe Ser Ile Met Lys Asn Thr Thr Asn Thr Arg Arg Gly Thr
2480 2485 2490
Gly Asn Ile Gly Glu Thr Leu Gly Glu Lys Trp Lys Ser Arg Leu
2495 2500 2505
Asn Ala Leu Gly Lys Ser Glu Phe Gln Ile Tyr Lys Lys Ser Gly
2510 2515 2520
Ile Gln Glu Val Asp Arg Thr Leu Ala Lys Glu Gly Ile Lys Arg
2525 2530 2535
Gly Glu Thr Asp His His Ala Val Ser Arg Gly Ser Ala Lys Leu
2540 2545 2550
Arg Trp Phe Val Glu Arg Asn Met Val Thr Pro Glu Gly Lys Val
2555 2560 2565
Val Asp Leu Gly Cys Gly Arg Gly Gly Trp Ser Tyr Tyr Cys Gly
2570 2575 2580
Gly Leu Lys Asn Val Arg Glu Val Lys Gly Leu Thr Lys Gly Gly
2585 2590 2595
Pro Gly His Glu Glu Pro Ile Pro Met Ser Thr Tyr Gly Trp Asn
2600 2605 2610
Leu Val Arg Leu Gln Ser Gly Val Asp Val Phe Phe Ile Pro Pro
2615 2620 2625
Glu Lys Cys Asp Thr Leu Leu Cys Asp Ile Gly Glu Ser Ser Pro
2630 2635 2640
Asn Pro Thr Val Glu Ala Gly Arg Thr Leu Arg Val Leu Asn Leu
2645 2650 2655
Val Glu Asn Trp Leu Asn Asn Asn Thr Gln Phe Cys Ile Lys Val
2660 2665 2670
Leu Asn Pro Tyr Met Pro Ser Val Ile Glu Lys Met Glu Ala Leu
2675 2680 2685
Gln Arg Lys Tyr Gly Gly Ala Leu Val Arg Asn Pro Leu Ser Arg
2690 2695 2700
Asn Ser Thr His Glu Met Tyr Trp Val Ser Asn Ala Ser Gly Asn
2705 2710 2715
Ile Val Ser Ser Val Asn Met Ile Ser Arg Met Leu Ile Asn Arg
2720 2725 2730
Phe Thr Met Arg Tyr Lys Lys Ala Thr Tyr Glu Pro Asp Val Asp
2735 2740 2745
Leu Gly Ser Gly Thr Arg Asn Ile Gly Ile Glu Ser Glu Ile Pro
2750 2755 2760
Asn Leu Asp Ile Ile Gly Lys Arg Ile Glu Lys Ile Lys Gln Glu
2765 2770 2775
His Glu Thr Ser Trp His Tyr Asp Gln Asp His Pro Tyr Lys Thr
2780 2785 2790
Trp Ala Tyr His Gly Ser Tyr Glu Thr Lys Gln Thr Gly Ser Ala
2795 2800 2805
Ser Ser Met Val Asn Gly Val Val Arg Leu Leu Thr Lys Pro Trp
2810 2815 2820
Asp Val Val Pro Met Val Thr Gln Met Ala Met Thr Asp Thr Thr
2825 2830 2835
Pro Phe Gly Gln Gln Arg Val Phe Lys Glu Lys Val Asp Thr Arg
2840 2845 2850
Thr Gln Glu Pro Lys Glu Gly Thr Lys Lys Leu Met Lys Ile Thr
2855 2860 2865
Ala Glu Trp Leu Trp Lys Glu Leu Gly Lys Lys Lys Thr Pro Arg
2870 2875 2880
Met Cys Thr Arg Glu Glu Phe Thr Arg Lys Val Arg Ser Asn Ala
2885 2890 2895
Ala Leu Gly Ala Ile Phe Thr Asp Glu Asn Lys Trp Lys Ser Ala
2900 2905 2910
Arg Glu Ala Val Glu Asp Ser Arg Phe Trp Glu Leu Val Asp Lys
2915 2920 2925
Glu Arg Asn Leu His Leu Glu Gly Lys Cys Glu Thr Cys Val Tyr
2930 2935 2940
Asn Met Met Gly Lys Arg Glu Lys Lys Leu Gly Glu Phe Gly Lys
2945 2950 2955
Ala Lys Gly Ser Arg Ala Ile Trp Tyr Met Trp Leu Gly Ala Arg
2960 2965 2970
Phe Leu Glu Phe Glu Ala Leu Gly Phe Leu Asn Glu Asp His Trp
2975 2980 2985
Phe Ser Arg Glu Asn Ser Leu Ser Gly Val Glu Gly Glu Gly Leu
2990 2995 3000
His Lys Leu Gly Tyr Ile Leu Arg Asp Val Ser Lys Lys Glu Gly
3005 3010 3015
Gly Ala Met Tyr Ala Asp Asp Thr Ala Gly Trp Asp Thr Arg Ile
3020 3025 3030
Thr Leu Glu Asp Leu Lys Asn Glu Glu Met Val Thr Asn His Met
3035 3040 3045
Glu Gly Glu His Lys Lys Leu Ala Glu Ala Ile Phe Lys Leu Thr
3050 3055 3060
Tyr Gln Asn Lys Val Val Arg Val Gln Arg Pro Thr Pro Arg Gly
3065 3070 3075
Thr Val Met Asp Ile Ile Ser Arg Arg Asp Gln Arg Gly Ser Gly
3080 3085 3090
Gln Val Gly Thr Tyr Gly Leu Asn Thr Phe Thr Asn Met Glu Ala
3095 3100 3105
Gln Leu Ile Arg Gln Met Glu Gly Glu Gly Val Phe Lys Ser Ile
3110 3115 3120
Gln His Leu Thr Ile Thr Glu Glu Ile Ala Val Gln Asn Trp Leu
3125 3130 3135
Ala Arg Val Gly Arg Glu Arg Leu Ser Arg Met Ala Ile Ser Gly
3140 3145 3150
Asp Asp Cys Val Val Lys Pro Leu Asp Asp Arg Phe Ala Ser Ala
3155 3160 3165
Leu Thr Ala Leu Asn Asp Met Gly Lys Ile Arg Lys Asp Ile Gln
3170 3175 3180
Gln Trp Glu Pro Ser Arg Gly Trp Asn Asp Trp Thr Gln Val Pro
3185 3190 3195
Phe Cys Ser His His Phe His Glu Leu Ile Met Lys Asp Gly Arg
3200 3205 3210
Val Leu Val Val Pro Cys Arg Asn Gln Asp Glu Leu Ile Gly Arg
3215 3220 3225
Ala Arg Ile Ser Gln Gly Ala Gly Trp Ser Leu Arg Glu Thr Ala
3230 3235 3240
Cys Leu Gly Lys Ser Tyr Ala Gln Met Trp Ser Leu Met Tyr Phe
3245 3250 3255
His Arg Arg Asp Leu Arg Leu Ala Ala Asn Ala Ile Cys Ser Ala
3260 3265 3270
Val Pro Ser His Trp Val Pro Thr Ser Arg Thr Thr Trp Ser Ile
3275 3280 3285
His Ala Lys His Glu Trp Met Thr Thr Glu Asp Met Leu Thr Val
3290 3295 3300
Trp Asn Arg Val Trp Ile Gln Glu Asn Pro Trp Met Glu Asp Lys
3305 3310 3315
Thr Pro Val Glu Ser Trp Glu Glu Ile Pro Tyr Leu Gly Lys Arg
3320 3325 3330
Glu Asp Gln Trp Cys Gly Ser Leu Ile Gly Leu Thr Ser Arg Ala
3335 3340 3345
Thr Trp Ala Lys Asn Ile Gln Ala Ala Ile Asn Gln Val Arg Ser
3350 3355 3360
Leu Ile Gly Asn Glu Glu Tyr Thr Asp Tyr Met Pro Ser Met Lys
3365 3370 3375
Arg Phe Arg Arg Glu Glu Glu Glu Ala Gly Val Leu Trp
3380 3385 3390
<210> 7
<211> 10699
<212> DNA
<213> 3型登革病毒
<220>
<221> CDS
<222> (95)..(10267)
<400> 7
agttgttagt ctacgtggac cgacaagaac agtttcgact cggaagcttg cttaacgtag 60
tgctgacagt tttttattag agagcagatc tctg atg aac aac caa cgg aaa aag 115
Met Asn Asn Gln Arg Lys Lys
1 5
acg gga aaa ccg tct atc aat atg ctg aaa cgc gtg aga aac cgt gtg 163
Thr Gly Lys Pro Ser Ile Asn Met Leu Lys Arg Val Arg Asn Arg Val
10 15 20
tca act gga tca cag ttg gcg aag aga ttc tca aga gga ttg ctg aac 211
Ser Thr Gly Ser Gln Leu Ala Lys Arg Phe Ser Arg Gly Leu Leu Asn
25 30 35
ggc caa gga cca atg aaa ttg gtt atg gca ttt ata gct ttc ctc aga 259
Gly Gln Gly Pro Met Lys Leu Val Met Ala Phe Ile Ala Phe Leu Arg
40 45 50 55
ttt cta gcc att cca ccg aca gca gga gtc ttg gct aga tgg ggt acc 307
Phe Leu Ala Ile Pro Pro Thr Ala Gly Val Leu Ala Arg Trp Gly Thr
60 65 70
ttt aag aag tcg ggg gct att aag gtc tta aaa ggc ttc aag aag gag 355
Phe Lys Lys Ser Gly Ala Ile Lys Val Leu Lys Gly Phe Lys Lys Glu
75 80 85
atc tca aac atg ctg agc att atc aac aaa cgg aaa aag aca tcg ctc 403
Ile Ser Asn Met Leu Ser Ile Ile Asn Lys Arg Lys Lys Thr Ser Leu
90 95 100
tgt ctc atg atg atg tta cca gca aca ctt gct ttc cac tta act tca 451
Cys Leu Met Met Met Leu Pro Ala Thr Leu Ala Phe His Leu Thr Ser
105 110 115
cga gat gga gag ccg cgc atg att gtg ggg aag aat gaa aga gga aaa 499
Arg Asp Gly Glu Pro Arg Met Ile Val Gly Lys Asn Glu Arg Gly Lys
120 125 130 135
tcc cta ctt ttc aag aca gcc tct gga atc aac atg tgc aca ctc ata 547
Ser Leu Leu Phe Lys Thr Ala Ser Gly Ile Asn Met Cys Thr Leu Ile
140 145 150
gcc atg gat ctg gga gag atg tgt gat gac acg gtc act tac aaa tgc 595
Ala Met Asp Leu Gly Glu Met Cys Asp Asp Thr Val Thr Tyr Lys Cys
155 160 165
ccc cac att acc gaa gtg gag cct gaa gac att gac tgc tgg tgc aac 643
Pro His Ile Thr Glu Val Glu Pro Glu Asp Ile Asp Cys Trp Cys Asn
170 175 180
ctt aca tcg aca tgg gtg act tat gga aca tgc aat caa gct gga gag 691
Leu Thr Ser Thr Trp Val Thr Tyr Gly Thr Cys Asn Gln Ala Gly Glu
185 190 195
cat aga cgc gat aag aga tca gtg gcg tta gct ccc cat gtt ggc atg 739
His Arg Arg Asp Lys Arg Ser Val Ala Leu Ala Pro His Val Gly Met
200 205 210 215
gga ctg gac aca cgc act caa acc tgg atg tcg gct gaa gga gct tgg 787
Gly Leu Asp Thr Arg Thr Gln Thr Trp Met Ser Ala Glu Gly Ala Trp
220 225 230
aga caa gtc gag aag gta gag aca tgg gcc ctt agg cac cca ggg ttt 835
Arg Gln Val Glu Lys Val Glu Thr Trp Ala Leu Arg His Pro Gly Phe
235 240 245
acc ata cta gcc cta ttt ctt gcc cat tac ata ggc act tcc ttg acc 883
Thr Ile Leu Ala Leu Phe Leu Ala His Tyr Ile Gly Thr Ser Leu Thr
250 255 260
cag aaa gtg gtt att ttt ata cta tta atg ctg gtt acc cca tcc atg 931
Gln Lys Val Val Ile Phe Ile Leu Leu Met Leu Val Thr Pro Ser Met
265 270 275
aca atg aga tgt gta gga gta gga aac aga gat ttt gtg gaa ggc cta 979
Thr Met Arg Cys Val Gly Val Gly Asn Arg Asp Phe Val Glu Gly Leu
280 285 290 295
tcg gga gct acg tgg gtt gac gtg gtg ctc gag cac ggt ggg tgt gtg 1027
Ser Gly Ala Thr Trp Val Asp Val Val Leu Glu His Gly Gly Cys Val
300 305 310
act acc atg gct aag aac aag ccc acg ctg gac ata gag ctt cag aag 1075
Thr Thr Met Ala Lys Asn Lys Pro Thr Leu Asp Ile Glu Leu Gln Lys
315 320 325
acc gag gcc acc caa ctg gcg acc cta agg aag cta tgc att gag gga 1123
Thr Glu Ala Thr Gln Leu Ala Thr Leu Arg Lys Leu Cys Ile Glu Gly
330 335 340
aaa att acc aac ata aca acc gac tca aga tgt ccc acc caa ggg gaa 1171
Lys Ile Thr Asn Ile Thr Thr Asp Ser Arg Cys Pro Thr Gln Gly Glu
345 350 355
gcg att tta cct gag gag cag gac cag aac tac gtg tgt aag cat aca 1219
Ala Ile Leu Pro Glu Glu Gln Asp Gln Asn Tyr Val Cys Lys His Thr
360 365 370 375
tac gtg gac aga ggc tgg gga aac ggt tgt ggt ttg ttt ggc aag gga 1267
Tyr Val Asp Arg Gly Trp Gly Asn Gly Cys Gly Leu Phe Gly Lys Gly
380 385 390
agc ttg gtg aca tgc gcg aaa ttt caa tgt tta gaa tca ata gag gga 1315
Ser Leu Val Thr Cys Ala Lys Phe Gln Cys Leu Glu Ser Ile Glu Gly
395 400 405
aaa gtg gtg caa cat gag aac ctc aaa tac acc gtc atc atc aca gtg 1363
Lys Val Val Gln His Glu Asn Leu Lys Tyr Thr Val Ile Ile Thr Val
410 415 420
cac aca gga gac caa cac cag gtg gga aat gaa acg cag gga gtc acg 1411
His Thr Gly Asp Gln His Gln Val Gly Asn Glu Thr Gln Gly Val Thr
425 430 435
gct gag ata aca ccc cag gca tca acc gct gaa gcc att tta cct gaa 1459
Ala Glu Ile Thr Pro Gln Ala Ser Thr Ala Glu Ala Ile Leu Pro Glu
440 445 450 455
tat gga acc ctc ggg cta gaa tgc tca cca cgg aca ggt ttg gat ttc 1507
Tyr Gly Thr Leu Gly Leu Glu Cys Ser Pro Arg Thr Gly Leu Asp Phe
460 465 470
aat gaa atg atc tca ttg aca atg aag aac aaa gca tgg atg gta cat 1555
Asn Glu Met Ile Ser Leu Thr Met Lys Asn Lys Ala Trp Met Val His
475 480 485
aga caa tgg ttc ttt gac tta ccc cta cca tgg aca tca gga gct aca 1603
Arg Gln Trp Phe Phe Asp Leu Pro Leu Pro Trp Thr Ser Gly Ala Thr
490 495 500
gca gaa aca cca act tgg aac agg aaa gag ctt ctt gtg aca ttt aaa 1651
Ala Glu Thr Pro Thr Trp Asn Arg Lys Glu Leu Leu Val Thr Phe Lys
505 510 515
aat gca cat gca aaa aag caa gaa gta gtt gtt ctt gga tca caa gag 1699
Asn Ala His Ala Lys Lys Gln Glu Val Val Val Leu Gly Ser Gln Glu
520 525 530 535
gga gca atg cat aca gca ctg aca gga gct aca gag atc caa acc tca 1747
Gly Ala Met His Thr Ala Leu Thr Gly Ala Thr Glu Ile Gln Thr Ser
540 545 550
gga ggc aca agt atc ttt gcg ggg cac tta aaa tgt aga ctc aag atg 1795
Gly Gly Thr Ser Ile Phe Ala Gly His Leu Lys Cys Arg Leu Lys Met
555 560 565
gac aaa ttg gaa ctc aag ggg atg agc tat gca atg tgc ttg agt agc 1843
Asp Lys Leu Glu Leu Lys Gly Met Ser Tyr Ala Met Cys Leu Ser Ser
570 575 580
ttt gtg ttg aag aaa gaa gtc tcc gaa acg cag cat ggg aca ata ctc 1891
Phe Val Leu Lys Lys Glu Val Ser Glu Thr Gln His Gly Thr Ile Leu
585 590 595
att aag gtt gag tac aaa ggg gaa gat gca ccc tgc aag att cct ttc 1939
Ile Lys Val Glu Tyr Lys Gly Glu Asp Ala Pro Cys Lys Ile Pro Phe
600 605 610 615
tcc acg gag gat gga caa gga aaa gct cac aat ggc aga ctg atc aca 1987
Ser Thr Glu Asp Gly Gln Gly Lys Ala His Asn Gly Arg Leu Ile Thr
620 625 630
gcc aat cca gtg gtg acc aag aag gag gag cct gtc aac att gag gct 2035
Ala Asn Pro Val Val Thr Lys Lys Glu Glu Pro Val Asn Ile Glu Ala
635 640 645
gaa cct cct ttt gga gaa agt aac ata gta att gga att gga gac aaa 2083
Glu Pro Pro Phe Gly Glu Ser Asn Ile Val Ile Gly Ile Gly Asp Lys
650 655 660
gcc ctg aaa atc aac tgg tac aag aag gga agc tcg att ggg aag atg 2131
Ala Leu Lys Ile Asn Trp Tyr Lys Lys Gly Ser Ser Ile Gly Lys Met
665 670 675
ttc gag gcc act gcc aga ggt gca agg cgc atg gcc atc ttg gga gac 2179
Phe Glu Ala Thr Ala Arg Gly Ala Arg Arg Met Ala Ile Leu Gly Asp
680 685 690 695
aca gcc tgg gac ttt gga tca gtg ggt ggt gtt ttg aat tca tta ggg 2227
Thr Ala Trp Asp Phe Gly Ser Val Gly Gly Val Leu Asn Ser Leu Gly
700 705 710
aaa atg gtc cac caa ata ttt ggg agt gct tac aca gcc cta ttt ggt 2275
Lys Met Val His Gln Ile Phe Gly Ser Ala Tyr Thr Ala Leu Phe Gly
715 720 725
gga gtc tcc tgg atg atg aaa att gga ata ggt gtc ctc tta acc tgg 2323
Gly Val Ser Trp Met Met Lys Ile Gly Ile Gly Val Leu Leu Thr Trp
730 735 740
ata ggg ttg aac tca aaa aat act tct atg tca ttt tca tgc atc gcg 2371
Ile Gly Leu Asn Ser Lys Asn Thr Ser Met Ser Phe Ser Cys Ile Ala
745 750 755
ata gga atc att aca ctc tat ctg gga gcc gtg gtg caa gct gac atg 2419
Ile Gly Ile Ile Thr Leu Tyr Leu Gly Ala Val Val Gln Ala Asp Met
760 765 770 775
ggg tgt gtc ata aac tgg aaa ggc aaa gaa ctc aaa tgt gga agt gga 2467
Gly Cys Val Ile Asn Trp Lys Gly Lys Glu Leu Lys Cys Gly Ser Gly
780 785 790
att ttc gtc act aat gag gtc cac acc tgg aca gag caa tac aaa ttt 2515
Ile Phe Val Thr Asn Glu Val His Thr Trp Thr Glu Gln Tyr Lys Phe
795 800 805
caa gca gac tcc ccc aag aga ctg gca aca gcc att gca ggc gct tgg 2563
Gln Ala Asp Ser Pro Lys Arg Leu Ala Thr Ala Ile Ala Gly Ala Trp
810 815 820
gaa aat gga gtg tgc gga att agg tca aca acc aga atg gag aac ctc 2611
Glu Asn Gly Val Cys Gly Ile Arg Ser Thr Thr Arg Met Glu Asn Leu
825 830 835
ttg tgg aag caa ata gcc aat gaa ctg aat tac ata tta tgg gaa aac 2659
Leu Trp Lys Gln Ile Ala Asn Glu Leu Asn Tyr Ile Leu Trp Glu Asn
840 845 850 855
aac att aaa tta acg gta gtt gta ggc gac ata act ggg gtc tta gag 2707
Asn Ile Lys Leu Thr Val Val Val Gly Asp Ile Thr Gly Val Leu Glu
860 865 870
caa ggg aaa aga aca cta aca cca caa ccc atg gag cta aaa tat tct 2755
Gln Gly Lys Arg Thr Leu Thr Pro Gln Pro Met Glu Leu Lys Tyr Ser
875 880 885
tgg aaa aca tgg gga aag gca aaa ata gtg aca gct gaa aca caa aat 2803
Trp Lys Thr Trp Gly Lys Ala Lys Ile Val Thr Ala Glu Thr Gln Asn
890 895 900
tcc tct ttc ata ata gat ggg cca agc aca ccg gag tgt cca agt gcc 2851
Ser Ser Phe Ile Ile Asp Gly Pro Ser Thr Pro Glu Cys Pro Ser Ala
905 910 915
tca aga gca tgg aat gtg tgg gag gtg gag gat tac ggg ttc gga gtt 2899
Ser Arg Ala Trp Asn Val Trp Glu Val Glu Asp Tyr Gly Phe Gly Val
920 925 930 935
ttc aca acc aac ata tgg ctg aaa ctc cga gag gtg tac acc caa cta 2947
Phe Thr Thr Asn Ile Trp Leu Lys Leu Arg Glu Val Tyr Thr Gln Leu
940 945 950
tgt gac cat agg cta atg tcg gca gcc gtc aag gat gag agg gct gta 2995
Cys Asp His Arg Leu Met Ser Ala Ala Val Lys Asp Glu Arg Ala Val
955 960 965
cat gcc gac atg ggc tat tgg ata gaa agc caa aag aat ggg agt tgg 3043
His Ala Asp Met Gly Tyr Trp Ile Glu Ser Gln Lys Asn Gly Ser Trp
970 975 980
aag cta gaa aaa gca tcc ttc ata gag gtg aaa acc tgc aca tgg cca 3091
Lys Leu Glu Lys Ala Ser Phe Ile Glu Val Lys Thr Cys Thr Trp Pro
985 990 995
aaa tca cac act ctc tgg agc aat ggt gtg cta gag agt gac atg 3136
Lys Ser His Thr Leu Trp Ser Asn Gly Val Leu Glu Ser Asp Met
1000 1005 1010
att atc cca aag agt cta gct ggt ccc att tcg caa cac aac cac 3181
Ile Ile Pro Lys Ser Leu Ala Gly Pro Ile Ser Gln His Asn His
1015 1020 1025
agg ccc ggg tac cac acc caa acg gca gga ccc tgg cac tta gga 3226
Arg Pro Gly Tyr His Thr Gln Thr Ala Gly Pro Trp His Leu Gly
1030 1035 1040
aaa ttg gag ctg gac ttc aac tat tgt gaa gga aca aca gtt gtc 3271
Lys Leu Glu Leu Asp Phe Asn Tyr Cys Glu Gly Thr Thr Val Val
1045 1050 1055
atc tca gaa aac tgt ggg aca aga ggc cca tca ttg aga aca aca 3316
Ile Ser Glu Asn Cys Gly Thr Arg Gly Pro Ser Leu Arg Thr Thr
1060 1065 1070
acg gtg tca ggg aag ttg ata cac gaa tgg tgc tgc cgc tcg tgc 3361
Thr Val Ser Gly Lys Leu Ile His Glu Trp Cys Cys Arg Ser Cys
1075 1080 1085
aca ctt cct ccc cta cga tac atg gga gaa gac ggc tgc tgg tat 3406
Thr Leu Pro Pro Leu Arg Tyr Met Gly Glu Asp Gly Cys Trp Tyr
1090 1095 1100
ggc atg gaa atc aga ccc att aat gag aaa gaa gag aat atg gta 3451
Gly Met Glu Ile Arg Pro Ile Asn Glu Lys Glu Glu Asn Met Val
1105 1110 1115
aag tct cta gcc tca gca ggg agt gga aag gtg gac aac ttc aca 3496
Lys Ser Leu Ala Ser Ala Gly Ser Gly Lys Val Asp Asn Phe Thr
1120 1125 1130
atg ggt gtc ttg tgt ttg gca atc ctc ttt gaa gag gtg atg aga 3541
Met Gly Val Leu Cys Leu Ala Ile Leu Phe Glu Glu Val Met Arg
1135 1140 1145
gga aaa ttt ggg aaa aaa cac atg att gca ggg gtt ctc ttc acg 3586
Gly Lys Phe Gly Lys Lys His Met Ile Ala Gly Val Leu Phe Thr
1150 1155 1160
ttt gtg ctc ctc ctc tca ggg caa ata aca tgg aga gac atg gcg 3631
Phe Val Leu Leu Leu Ser Gly Gln Ile Thr Trp Arg Asp Met Ala
1165 1170 1175
cac aca ctc ata atg att ggg tcc aac gcc tct gac aga atg ggg 3676
His Thr Leu Ile Met Ile Gly Ser Asn Ala Ser Asp Arg Met Gly
1180 1185 1190
atg ggc gtc act tac cta gct cta att gca aca ttt aaa att cag 3721
Met Gly Val Thr Tyr Leu Ala Leu Ile Ala Thr Phe Lys Ile Gln
1195 1200 1205
cca ttc ctg gct ttg gga ttc ttc ctg agg aaa ctg aca tct aga 3766
Pro Phe Leu Ala Leu Gly Phe Phe Leu Arg Lys Leu Thr Ser Arg
1210 1215 1220
gaa aat tta ttg ctg gga gtt ggg ttg gcc atg gca gca acg tta 3811
Glu Asn Leu Leu Leu Gly Val Gly Leu Ala Met Ala Ala Thr Leu
1225 1230 1235
cga ctg cca gag gac att gaa cag atg gcg aat gga att gct ttg 3856
Arg Leu Pro Glu Asp Ile Glu Gln Met Ala Asn Gly Ile Ala Leu
1240 1245 1250
ggg ctc atg gct ctt aaa ctg ata aca caa ttt gaa aca tac caa 3901
Gly Leu Met Ala Leu Lys Leu Ile Thr Gln Phe Glu Thr Tyr Gln
1255 1260 1265
cta tgg acg gca tta gtt tcc cta acg tgt tca aat aca att ttc 3946
Leu Trp Thr Ala Leu Val Ser Leu Thr Cys Ser Asn Thr Ile Phe
1270 1275 1280
acg ttg act gtt gcc tgg aga aca gcc act ctg att tta gcc gga 3991
Thr Leu Thr Val Ala Trp Arg Thr Ala Thr Leu Ile Leu Ala Gly
1285 1290 1295
att tcg ctt ttg cca gtg tgc cag tct tcg agc atg agg aaa aca 4036
Ile Ser Leu Leu Pro Val Cys Gln Ser Ser Ser Met Arg Lys Thr
1300 1305 1310
gat tgg ctc cca atg act gtg gca gct atg gga gct caa ccc cta 4081
Asp Trp Leu Pro Met Thr Val Ala Ala Met Gly Ala Gln Pro Leu
1315 1320 1325
cca ctt ttt att ttc agt ctg aaa gat aca ctc aaa agg aga agc 4126
Pro Leu Phe Ile Phe Ser Leu Lys Asp Thr Leu Lys Arg Arg Ser
1330 1335 1340
tgg cca ctg aat gag ggg gtg atg gca gtt gga ctt gtg agc att 4171
Trp Pro Leu Asn Glu Gly Val Met Ala Val Gly Leu Val Ser Ile
1345 1350 1355
cta gct agt tct ctc ctt agg aat gat gtg cct atg gct gga cca 4216
Leu Ala Ser Ser Leu Leu Arg Asn Asp Val Pro Met Ala Gly Pro
1360 1365 1370
tta gtg gct ggg ggc ttg ctg ata gcg tgc tac gtc ata act ggc 4261
Leu Val Ala Gly Gly Leu Leu Ile Ala Cys Tyr Val Ile Thr Gly
1375 1380 1385
acg tca gca gac ctc act gta gaa aaa gca gca gat gta aca tgg 4306
Thr Ser Ala Asp Leu Thr Val Glu Lys Ala Ala Asp Val Thr Trp
1390 1395 1400
gag gaa gag gcc gag caa aca gga gtg tcc cac aat tta atg gtc 4351
Glu Glu Glu Ala Glu Gln Thr Gly Val Ser His Asn Leu Met Val
1405 1410 1415
aca gtt gat gat gat gga aca atg aga ata aaa gat gac gag act 4396
Thr Val Asp Asp Asp Gly Thr Met Arg Ile Lys Asp Asp Glu Thr
1420 1425 1430
gag aac atc tta aca gtg ctt tta aaa aca gca cta cta ata gta 4441
Glu Asn Ile Leu Thr Val Leu Leu Lys Thr Ala Leu Leu Ile Val
1435 1440 1445
tca ggc atc ttt cca tac tcc ata ccc gca aca ctg ttg gtc tgg 4486
Ser Gly Ile Phe Pro Tyr Ser Ile Pro Ala Thr Leu Leu Val Trp
1450 1455 1460
cat act tgg caa aag caa acc caa aga tcc ggc gtc cta tgg gac 4531
His Thr Trp Gln Lys Gln Thr Gln Arg Ser Gly Val Leu Trp Asp
1465 1470 1475
gta ccc agc ccc cca gag aca cag aaa gcg gaa ctg gaa gaa ggg 4576
Val Pro Ser Pro Pro Glu Thr Gln Lys Ala Glu Leu Glu Glu Gly
1480 1485 1490
gtc tat agg atc aaa cag caa gga att ttt ggg aaa acc caa gtg 4621
Val Tyr Arg Ile Lys Gln Gln Gly Ile Phe Gly Lys Thr Gln Val
1495 1500 1505
ggg gtt gga gta cag aaa gaa gga gtt ttc cac acc atg tgg cat 4666
Gly Val Gly Val Gln Lys Glu Gly Val Phe His Thr Met Trp His
1510 1515 1520
gtc aca aga ggg gca gtg ttg aca cac aat ggg aaa aga ctg gaa 4711
Val Thr Arg Gly Ala Val Leu Thr His Asn Gly Lys Arg Leu Glu
1525 1530 1535
cca aac tgg gct agc gtg aaa aaa gat ctg att tca tac gga gga 4756
Pro Asn Trp Ala Ser Val Lys Lys Asp Leu Ile Ser Tyr Gly Gly
1540 1545 1550
gga tgg aga ttg agt gca caa tgg caa aag ggg gag gag gtg cag 4801
Gly Trp Arg Leu Ser Ala Gln Trp Gln Lys Gly Glu Glu Val Gln
1555 1560 1565
gtt att gcc gta gag cct ggg aag aac cca aag aac ttt caa acc 4846
Val Ile Ala Val Glu Pro Gly Lys Asn Pro Lys Asn Phe Gln Thr
1570 1575 1580
atg cca ggc att ttt cag aca aca aca ggg gaa ata gga gca att 4891
Met Pro Gly Ile Phe Gln Thr Thr Thr Gly Glu Ile Gly Ala Ile
1585 1590 1595
gca ctg gat ttc aag cct gga act tca gga tct ccc atc ata aac 4936
Ala Leu Asp Phe Lys Pro Gly Thr Ser Gly Ser Pro Ile Ile Asn
1600 1605 1610
aga gag gga aag gta gtg gga ctg tat ggc aat gga gtg gtt aca 4981
Arg Glu Gly Lys Val Val Gly Leu Tyr Gly Asn Gly Val Val Thr
1615 1620 1625
aag aat gga ggc tat gtc agt gga ata gcg caa aca aat gca gaa 5026
Lys Asn Gly Gly Tyr Val Ser Gly Ile Ala Gln Thr Asn Ala Glu
1630 1635 1640
cca gat gga ccg aca cca gag ttg gaa gaa gag atg ttc aaa aag 5071
Pro Asp Gly Pro Thr Pro Glu Leu Glu Glu Glu Met Phe Lys Lys
1645 1650 1655
cga aat cta acc ata atg gat ctc cat cct ggg tca gga aag acg 5116
Arg Asn Leu Thr Ile Met Asp Leu His Pro Gly Ser Gly Lys Thr
1660 1665 1670
cgg aaa tat ctt cca gct att gtt aga gag gca atc aag aga cgc 5161
Arg Lys Tyr Leu Pro Ala Ile Val Arg Glu Ala Ile Lys Arg Arg
1675 1680 1685
tta agg act cta att ttg gca cca aca agg gta gtt gca gct gag 5206
Leu Arg Thr Leu Ile Leu Ala Pro Thr Arg Val Val Ala Ala Glu
1690 1695 1700
atg gaa gaa gca ttg aaa ggg ctc cca ata agg tat caa aca act 5251
Met Glu Glu Ala Leu Lys Gly Leu Pro Ile Arg Tyr Gln Thr Thr
1705 1710 1715
gca aca aaa tct gaa cac aca gga aga gag att gtt gat cta atg 5296
Ala Thr Lys Ser Glu His Thr Gly Arg Glu Ile Val Asp Leu Met
1720 1725 1730
tgt cac gca acg ttc aca atg cgc ttg ctg tca cca gtc agg gtt 5341
Cys His Ala Thr Phe Thr Met Arg Leu Leu Ser Pro Val Arg Val
1735 1740 1745
cca aac tac aac ttg ata ata atg gat gag gcc cat ttc aca gac 5386
Pro Asn Tyr Asn Leu Ile Ile Met Asp Glu Ala His Phe Thr Asp
1750 1755 1760
cca gcc agt ata gcg gct aga ggg tac ata tca act cgt gta gga 5431
Pro Ala Ser Ile Ala Ala Arg Gly Tyr Ile Ser Thr Arg Val Gly
1765 1770 1775
atg gga gag gca gcc gca att ttc atg aca gca aca ccc cct gga 5476
Met Gly Glu Ala Ala Ala Ile Phe Met Thr Ala Thr Pro Pro Gly
1780 1785 1790
aca gct gat gcc ttt cct cag agc aac gct cca att caa gat gaa 5521
Thr Ala Asp Ala Phe Pro Gln Ser Asn Ala Pro Ile Gln Asp Glu
1795 1800 1805
gag aga gac ata ccg gaa cgc tca tgg aat tca ggc aat gaa tgg 5566
Glu Arg Asp Ile Pro Glu Arg Ser Trp Asn Ser Gly Asn Glu Trp
1810 1815 1820
att act gac ttt gtt ggg aag aca gtg tgg ttt gtc cct agc atc 5611
Ile Thr Asp Phe Val Gly Lys Thr Val Trp Phe Val Pro Ser Ile
1825 1830 1835
aaa gcc gga aat gac ata gca aac tgc ttg cgg aaa aat gga aaa 5656
Lys Ala Gly Asn Asp Ile Ala Asn Cys Leu Arg Lys Asn Gly Lys
1840 1845 1850
aag gtt att caa ctc agc agg aag acc ttt gac aca gaa tat caa 5701
Lys Val Ile Gln Leu Ser Arg Lys Thr Phe Asp Thr Glu Tyr Gln
1855 1860 1865
aag acc aaa ctg aat gat tgg gac ttt gtg gtg aca aca gac att 5746
Lys Thr Lys Leu Asn Asp Trp Asp Phe Val Val Thr Thr Asp Ile
1870 1875 1880
tca gaa atg gga gcc aat ttc aaa gca gat aga gtg atc gac cca 5791
Ser Glu Met Gly Ala Asn Phe Lys Ala Asp Arg Val Ile Asp Pro
1885 1890 1895
aga aga tgt ctc aag ccg gtg att ttg aca gat gga ccc gag cgg 5836
Arg Arg Cys Leu Lys Pro Val Ile Leu Thr Asp Gly Pro Glu Arg
1900 1905 1910
gtg atc ctg gct gga cca atg cca gtc acc gta gcg agc gct gcg 5881
Val Ile Leu Ala Gly Pro Met Pro Val Thr Val Ala Ser Ala Ala
1915 1920 1925
caa agg aga ggg aga gtt ggc agg aac cca caa aaa gaa aat gac 5926
Gln Arg Arg Gly Arg Val Gly Arg Asn Pro Gln Lys Glu Asn Asp
1930 1935 1940
cag tac ata ttc atg ggc cag cct ctc aac aat gat gaa gac cat 5971
Gln Tyr Ile Phe Met Gly Gln Pro Leu Asn Asn Asp Glu Asp His
1945 1950 1955
gct cac tgg aca gaa gca aaa atg ctg ctg gac aac atc aac aca 6016
Ala His Trp Thr Glu Ala Lys Met Leu Leu Asp Asn Ile Asn Thr
1960 1965 1970
cca gaa ggg att ata cca gct ctc ttt gaa cca gaa agg gag aag 6061
Pro Glu Gly Ile Ile Pro Ala Leu Phe Glu Pro Glu Arg Glu Lys
1975 1980 1985
tca gcc gcc ata gac ggc gaa tac cgc ctg aag ggt gag tcc agg 6106
Ser Ala Ala Ile Asp Gly Glu Tyr Arg Leu Lys Gly Glu Ser Arg
1990 1995 2000
aag act ttc gtg gaa ctc atg agg agg ggt gac ctc cca gtt tgg 6151
Lys Thr Phe Val Glu Leu Met Arg Arg Gly Asp Leu Pro Val Trp
2005 2010 2015
cta gcc cat aaa gta gca tca gaa ggg atc aaa tat aca gat aga 6196
Leu Ala His Lys Val Ala Ser Glu Gly Ile Lys Tyr Thr Asp Arg
2020 2025 2030
aaa tgg tgc ttt gat gga gaa cgt aat aat caa att tta gag gag 6241
Lys Trp Cys Phe Asp Gly Glu Arg Asn Asn Gln Ile Leu Glu Glu
2035 2040 2045
aat atg gat gtg gaa atc tgg aca aag gaa gga gaa aag aaa aaa 6286
Asn Met Asp Val Glu Ile Trp Thr Lys Glu Gly Glu Lys Lys Lys
2050 2055 2060
ctg aga cct agg tgg ctt gat gcc cgc act tat tca gat cct tta 6331
Leu Arg Pro Arg Trp Leu Asp Ala Arg Thr Tyr Ser Asp Pro Leu
2065 2070 2075
gca ctc aaa gaa ttc aag gat ttt gca gct ggc aga aag tca atc 6376
Ala Leu Lys Glu Phe Lys Asp Phe Ala Ala Gly Arg Lys Ser Ile
2080 2085 2090
gcc ctt gat ctt gtg aca gaa ata gga aga gtg cct tca cac tta 6421
Ala Leu Asp Leu Val Thr Glu Ile Gly Arg Val Pro Ser His Leu
2095 2100 2105
gcc cac aga acg aga aac gcc ctg gat aat ttg gtg atg ctg cac 6466
Ala His Arg Thr Arg Asn Ala Leu Asp Asn Leu Val Met Leu His
2110 2115 2120
acg tca gaa cat ggc ggt agg gcc tac agg cat gca gtg gag gaa 6511
Thr Ser Glu His Gly Gly Arg Ala Tyr Arg His Ala Val Glu Glu
2125 2130 2135
cta cca gaa acg atg gaa aca ctc tta ctc ctg gga ctg atg atc 6556
Leu Pro Glu Thr Met Glu Thr Leu Leu Leu Leu Gly Leu Met Ile
2140 2145 2150
ttg tta aca ggt gga gca atg ctc ttc ttg ata tca ggt aaa ggg 6601
Leu Leu Thr Gly Gly Ala Met Leu Phe Leu Ile Ser Gly Lys Gly
2155 2160 2165
att gga aag act tca ata gga ctc att tgt gta att gct tcc agc 6646
Ile Gly Lys Thr Ser Ile Gly Leu Ile Cys Val Ile Ala Ser Ser
2170 2175 2180
ggc atg tta tgg atg gct gat gtc cca ctc caa tgg atc gca tcg 6691
Gly Met Leu Trp Met Ala Asp Val Pro Leu Gln Trp Ile Ala Ser
2185 2190 2195
gct ata gtc ctg gag ttt ttt atg atg gtg ttg ctc ata cca gaa 6736
Ala Ile Val Leu Glu Phe Phe Met Met Val Leu Leu Ile Pro Glu
2200 2205 2210
cca gaa aag cag aga act ccc caa gac aac caa ctc gca tat gtc 6781
Pro Glu Lys Gln Arg Thr Pro Gln Asp Asn Gln Leu Ala Tyr Val
2215 2220 2225
gtg ata ggc ata ctt aca ttg gct gca ata gta gcg gcc aat gaa 6826
Val Ile Gly Ile Leu Thr Leu Ala Ala Ile Val Ala Ala Asn Glu
2230 2235 2240
atg gga ctg ttg gaa act aca aag aga gat tta gga atg tct aaa 6871
Met Gly Leu Leu Glu Thr Thr Lys Arg Asp Leu Gly Met Ser Lys
2245 2250 2255
gaa cca ggt gtt gtt tct cca acc agc tat ttg gat gtg gac ttg 6916
Glu Pro Gly Val Val Ser Pro Thr Ser Tyr Leu Asp Val Asp Leu
2260 2265 2270
cac cca gca tca gcc tgg aca ttg tac gcc gtg gcc aca aca gta 6961
His Pro Ala Ser Ala Trp Thr Leu Tyr Ala Val Ala Thr Thr Val
2275 2280 2285
ata aca cca atg ttg aga cac acc ata gag aat tcc aca gca aat 7006
Ile Thr Pro Met Leu Arg His Thr Ile Glu Asn Ser Thr Ala Asn
2290 2295 2300
gtg tct ctg gca gcc ata gct aac cag gca gtg gtc ctg atg ggt 7051
Val Ser Leu Ala Ala Ile Ala Asn Gln Ala Val Val Leu Met Gly
2305 2310 2315
tta gac aaa gga tgg ccg ata tcg aaa atg gac ttg ggc gta cca 7096
Leu Asp Lys Gly Trp Pro Ile Ser Lys Met Asp Leu Gly Val Pro
2320 2325 2330
cta ttg gca ctg ggt tgc tat tca caa gtg aac cca cta act ctt 7141
Leu Leu Ala Leu Gly Cys Tyr Ser Gln Val Asn Pro Leu Thr Leu
2335 2340 2345
gca gcg gca gta ctt ttg cta gtc aca cat tat gca att ata ggt 7186
Ala Ala Ala Val Leu Leu Leu Val Thr His Tyr Ala Ile Ile Gly
2350 2355 2360
cca gga ttg cag gca aaa gcc acc cgt gaa gct cag aaa agg aca 7231
Pro Gly Leu Gln Ala Lys Ala Thr Arg Glu Ala Gln Lys Arg Thr
2365 2370 2375
gct gct gga ata atg aag aat cca acg gtg gat gga ata atg aca 7276
Ala Ala Gly Ile Met Lys Asn Pro Thr Val Asp Gly Ile Met Thr
2380 2385 2390
ata gac cta gat cct gta ata tat gat tca aaa ttt gaa aag caa 7321
Ile Asp Leu Asp Pro Val Ile Tyr Asp Ser Lys Phe Glu Lys Gln
2395 2400 2405
cta gga cag gtc atg ctc ctg gtt ctg tgt gca gtc caa ctt tta 7366
Leu Gly Gln Val Met Leu Leu Val Leu Cys Ala Val Gln Leu Leu
2410 2415 2420
ttg atg aga aca tca tgg gcc ttg tgt gaa gtt cta acc cta gcc 7411
Leu Met Arg Thr Ser Trp Ala Leu Cys Glu Val Leu Thr Leu Ala
2425 2430 2435
aca gga cca ata aca aca ctc tgg gaa gga tca cct ggg aag ttc 7456
Thr Gly Pro Ile Thr Thr Leu Trp Glu Gly Ser Pro Gly Lys Phe
2440 2445 2450
tgg aac acc acg ata gct gtt tcc atg gcg aac atc ttt aga ggg 7501
Trp Asn Thr Thr Ile Ala Val Ser Met Ala Asn Ile Phe Arg Gly
2455 2460 2465
agc tat tta gca gga gct ggg ctt gct ttt tct atc atg aaa tca 7546
Ser Tyr Leu Ala Gly Ala Gly Leu Ala Phe Ser Ile Met Lys Ser
2470 2475 2480
gtt gga aca gga aag aga gga aca ggg tca caa ggt gaa acc tta 7591
Val Gly Thr Gly Lys Arg Gly Thr Gly Ser Gln Gly Glu Thr Leu
2485 2490 2495
gga gaa aag tgg aaa aag aaa tta aat cag tta tcc cgg aaa gag 7636
Gly Glu Lys Trp Lys Lys Lys Leu Asn Gln Leu Ser Arg Lys Glu
2500 2505 2510
ttt gac ctt tac aag aaa tcc gga atc acc gaa gtg gat aga aca 7681
Phe Asp Leu Tyr Lys Lys Ser Gly Ile Thr Glu Val Asp Arg Thr
2515 2520 2525
gaa gcc aaa gaa ggg tta aaa aga gga gaa ata aca cac cat gcc 7726
Glu Ala Lys Glu Gly Leu Lys Arg Gly Glu Ile Thr His His Ala
2530 2535 2540
gtg tcc aga ggc agc gca aaa ctt caa tgg ttc gtg gag aga aac 7771
Val Ser Arg Gly Ser Ala Lys Leu Gln Trp Phe Val Glu Arg Asn
2545 2550 2555
atg gtc att cct gaa gga aga gtc ata gac cta ggc tgt gga aga 7816
Met Val Ile Pro Glu Gly Arg Val Ile Asp Leu Gly Cys Gly Arg
2560 2565 2570
gga ggc tgg tca tat tac tgt gca gga ctg aaa aaa gtt aca gaa 7861
Gly Gly Trp Ser Tyr Tyr Cys Ala Gly Leu Lys Lys Val Thr Glu
2575 2580 2585
gtg cga gga tac aca aaa ggc ggc cca gga cac gaa gaa cca gta 7906
Val Arg Gly Tyr Thr Lys Gly Gly Pro Gly His Glu Glu Pro Val
2590 2595 2600
cct atg tct aca tac gga tgg aac ata gtc aag tta atg agt gga 7951
Pro Met Ser Thr Tyr Gly Trp Asn Ile Val Lys Leu Met Ser Gly
2605 2610 2615
aag gat gtt ttt tat ctg cca cct gaa aag tgt gat acc cta ttg 7996
Lys Asp Val Phe Tyr Leu Pro Pro Glu Lys Cys Asp Thr Leu Leu
2620 2625 2630
tgt gac att gga gaa tct tca cca agc cca aca gtg gaa gaa agc 8041
Cys Asp Ile Gly Glu Ser Ser Pro Ser Pro Thr Val Glu Glu Ser
2635 2640 2645
aga acc ata aga gtt ttg aag atg gtt gaa cca tgg cta aag aac 8086
Arg Thr Ile Arg Val Leu Lys Met Val Glu Pro Trp Leu Lys Asn
2650 2655 2660
aac cag ttt tgc att aaa gta ttg aac cca tac atg cca act gtg 8131
Asn Gln Phe Cys Ile Lys Val Leu Asn Pro Tyr Met Pro Thr Val
2665 2670 2675
att gag cac tta gaa aga cta caa agg aaa cat gga gga atg ctt 8176
Ile Glu His Leu Glu Arg Leu Gln Arg Lys His Gly Gly Met Leu
2680 2685 2690
gtg aga aat cca ctc tca cga aac tcc acg cac gaa atg tat tgg 8221
Val Arg Asn Pro Leu Ser Arg Asn Ser Thr His Glu Met Tyr Trp
2695 2700 2705
ata tcc aat ggt aca ggc aat atc gtc tct tca gtc aac atg gta 8266
Ile Ser Asn Gly Thr Gly Asn Ile Val Ser Ser Val Asn Met Val
2710 2715 2720
tcc aga ttg cta ctg aac aga ttc aca atg aca cac agg aga ccc 8311
Ser Arg Leu Leu Leu Asn Arg Phe Thr Met Thr His Arg Arg Pro
2725 2730 2735
acc ata gag aaa gat gtg gat cta gga gca gga acc cga cat gtc 8356
Thr Ile Glu Lys Asp Val Asp Leu Gly Ala Gly Thr Arg His Val
2740 2745 2750
aat gcg gaa cca gaa aca ccc aac atg gat gtc att ggg gaa aga 8401
Asn Ala Glu Pro Glu Thr Pro Asn Met Asp Val Ile Gly Glu Arg
2755 2760 2765
ata aaa agg atc aaa gag gag cat agt tca aca tgg cac tat gat 8446
Ile Lys Arg Ile Lys Glu Glu His Ser Ser Thr Trp His Tyr Asp
2770 2775 2780
gat gaa aat cct tac aaa acg tgg gct tac cat gga tcc tat gaa 8491
Asp Glu Asn Pro Tyr Lys Thr Trp Ala Tyr His Gly Ser Tyr Glu
2785 2790 2795
gta aaa gcc aca ggc tca gcc tcc tcc atg ata aat gga gtc gtg 8536
Val Lys Ala Thr Gly Ser Ala Ser Ser Met Ile Asn Gly Val Val
2800 2805 2810
aaa ctc ctc aca aaa cca tgg gat gtg gtg ccc atg gtg aca cag 8581
Lys Leu Leu Thr Lys Pro Trp Asp Val Val Pro Met Val Thr Gln
2815 2820 2825
atg gca atg aca gat aca act cca ttc ggc cag caa aga gtt ttt 8626
Met Ala Met Thr Asp Thr Thr Pro Phe Gly Gln Gln Arg Val Phe
2830 2835 2840
aaa gag aaa gtg gac acc agg aca cct agg ccc atg cca gga aca 8671
Lys Glu Lys Val Asp Thr Arg Thr Pro Arg Pro Met Pro Gly Thr
2845 2850 2855
aga aag gtt atg gag atc aca gcg gag tgg ctt tgg agg acc ctg 8716
Arg Lys Val Met Glu Ile Thr Ala Glu Trp Leu Trp Arg Thr Leu
2860 2865 2870
gga agg aac aaa aga ccc aga tta tgc aca agg gag gaa ttc aca 8761
Gly Arg Asn Lys Arg Pro Arg Leu Cys Thr Arg Glu Glu Phe Thr
2875 2880 2885
aag aag gtc aga acc aac gca gct atg ggc gct gtc ttc aca gaa 8806
Lys Lys Val Arg Thr Asn Ala Ala Met Gly Ala Val Phe Thr Glu
2890 2895 2900
gag aac caa tgg gac agt gcg aga gct gct gtt gag gac gaa gaa 8851
Glu Asn Gln Trp Asp Ser Ala Arg Ala Ala Val Glu Asp Glu Glu
2905 2910 2915
ttt tgg aaa ctt gtg gac aga gaa cgt gaa ctc cac aaa ctg ggc 8896
Phe Trp Lys Leu Val Asp Arg Glu Arg Glu Leu His Lys Leu Gly
2920 2925 2930
aag tgt gga agc tgc gtt tac aac atg atg ggc aag aga gag aaa 8941
Lys Cys Gly Ser Cys Val Tyr Asn Met Met Gly Lys Arg Glu Lys
2935 2940 2945
aaa ctt gga gag ttt ggt aaa gca aaa ggc agt agg gct ata tgg 8986
Lys Leu Gly Glu Phe Gly Lys Ala Lys Gly Ser Arg Ala Ile Trp
2950 2955 2960
tac atg tgg ttg gga gcc agg tac ctt gag ttc gag gcg ctc gga 9031
Tyr Met Trp Leu Gly Ala Arg Tyr Leu Glu Phe Glu Ala Leu Gly
2965 2970 2975
ttc ctc aat gaa gac cac tgg ttc tcg cgt gaa aac tct tac agt 9076
Phe Leu Asn Glu Asp His Trp Phe Ser Arg Glu Asn Ser Tyr Ser
2980 2985 2990
gga gta gaa gga gaa gga ctg cac aag ctg gga tac atc ttg aga 9121
Gly Val Glu Gly Glu Gly Leu His Lys Leu Gly Tyr Ile Leu Arg
2995 3000 3005
gat att tcc aag ata ccc gga gga gcc atg tat gct gat gac aca 9166
Asp Ile Ser Lys Ile Pro Gly Gly Ala Met Tyr Ala Asp Asp Thr
3010 3015 3020
gcc ggt tgg gac aca aga ata aca gaa gat gac ctg cac aat gag 9211
Ala Gly Trp Asp Thr Arg Ile Thr Glu Asp Asp Leu His Asn Glu
3025 3030 3035
gaa aaa atc aca cag cag atg gac cct gaa cac agg cag cta gcg 9256
Glu Lys Ile Thr Gln Gln Met Asp Pro Glu His Arg Gln Leu Ala
3040 3045 3050
aac gct ata ttc aag ctc aca tac caa aac aaa gtg gtc aaa gtc 9301
Asn Ala Ile Phe Lys Leu Thr Tyr Gln Asn Lys Val Val Lys Val
3055 3060 3065
caa cga cca act cca aag ggc acg gta atg gac atc ata tct agg 9346
Gln Arg Pro Thr Pro Lys Gly Thr Val Met Asp Ile Ile Ser Arg
3070 3075 3080
aaa gac caa aga ggc agt gga cag gtg gga act tat ggt ctg aac 9391
Lys Asp Gln Arg Gly Ser Gly Gln Val Gly Thr Tyr Gly Leu Asn
3085 3090 3095
aca ttc acc aac atg gaa gcc cag cta atc aga caa atg gaa gga 9436
Thr Phe Thr Asn Met Glu Ala Gln Leu Ile Arg Gln Met Glu Gly
3100 3105 3110
gaa ggc gtg ttg tca aag gca gac ctc gag aac ccc cat ccg cta 9481
Glu Gly Val Leu Ser Lys Ala Asp Leu Glu Asn Pro His Pro Leu
3115 3120 3125
gag aag aaa att aca caa tgg ttg gaa act aaa gga gtg gaa agg 9526
Glu Lys Lys Ile Thr Gln Trp Leu Glu Thr Lys Gly Val Glu Arg
3130 3135 3140
tta aaa aga atg gcc atc agc ggg gat gat tgc gtt gtg aaa cca 9571
Leu Lys Arg Met Ala Ile Ser Gly Asp Asp Cys Val Val Lys Pro
3145 3150 3155
atc gac gac aga ttc gcc aat gcc ctg ctt gcc ctg aac gat atg 9616
Ile Asp Asp Arg Phe Ala Asn Ala Leu Leu Ala Leu Asn Asp Met
3160 3165 3170
gga aag gtt aga aag gac ata cct caa tgg cag cca tca aag gga 9661
Gly Lys Val Arg Lys Asp Ile Pro Gln Trp Gln Pro Ser Lys Gly
3175 3180 3185
tgg cat gat tgg caa cag gtc ccc ttc tgc tcc cac cac ttt cat 9706
Trp His Asp Trp Gln Gln Val Pro Phe Cys Ser His His Phe His
3190 3195 3200
gaa ttg atc atg aaa gat gga aga aag ttg gta gtt ccc tgc aga 9751
Glu Leu Ile Met Lys Asp Gly Arg Lys Leu Val Val Pro Cys Arg
3205 3210 3215
ccc cag gac gaa cta ata gga aga gcg aga atc tcc caa gga gca 9796
Pro Gln Asp Glu Leu Ile Gly Arg Ala Arg Ile Ser Gln Gly Ala
3220 3225 3230
gga tgg agc ctt aga gaa act gca tgt cta ggg aaa gcc tac gct 9841
Gly Trp Ser Leu Arg Glu Thr Ala Cys Leu Gly Lys Ala Tyr Ala
3235 3240 3245
caa atg tgg gct ctc atg tat ttt cac aga aga gat ctt aga cta 9886
Gln Met Trp Ala Leu Met Tyr Phe His Arg Arg Asp Leu Arg Leu
3250 3255 3260
gca tcc aac gcc ata tgt tca gca gta cca gtc cac tgg gtc ccc 9931
Ala Ser Asn Ala Ile Cys Ser Ala Val Pro Val His Trp Val Pro
3265 3270 3275
acg agc aga acg aca tgg tct att cat gct cac cat cag tgg atg 9976
Thr Ser Arg Thr Thr Trp Ser Ile His Ala His His Gln Trp Met
3280 3285 3290
act aca gaa gac atg ctt act gtc tgg aac agg gtg tgg ata gag 10021
Thr Thr Glu Asp Met Leu Thr Val Trp Asn Arg Val Trp Ile Glu
3295 3300 3305
gac aat cca tgg atg gaa gac aaa act cca gtc aca acg tgg gaa 10066
Asp Asn Pro Trp Met Glu Asp Lys Thr Pro Val Thr Thr Trp Glu
3310 3315 3320
gat gtt cca tat cta ggg aag aga gaa gac caa tgg tgc gga tca 10111
Asp Val Pro Tyr Leu Gly Lys Arg Glu Asp Gln Trp Cys Gly Ser
3325 3330 3335
ctc ata ggt ctc act tcc aga gca acc tgg gcc cag aac ata ctc 10156
Leu Ile Gly Leu Thr Ser Arg Ala Thr Trp Ala Gln Asn Ile Leu
3340 3345 3350
aca gca atc caa cag gtg aga agc ctc ata ggc aat gaa gag ttt 10201
Thr Ala Ile Gln Gln Val Arg Ser Leu Ile Gly Asn Glu Glu Phe
3355 3360 3365
ctg gac tac atg cct tcg atg aag aga ttc agg aag gag gag gag 10246
Leu Asp Tyr Met Pro Ser Met Lys Arg Phe Arg Lys Glu Glu Glu
3370 3375 3380
tca gag gga gcc att tgg taa aagcaggagg taaactgtca ggccacatta 10297
Ser Glu Gly Ala Ile Trp
3385 3390
agccacagta cggaagaagc tgtgcagcct gtgagccccg tccaaggacg ttaaaagaag10357
aagtcaggcc caaaagccac ggtttgagca aaccgtgctg cctgtagctc cgtcgtgggg10417
acgtaaagcc tgggaggctg caaaccgtgg aagctgtacg cacggtgtag cagactagtg10477
gttagaggag acccctccca tgacacaacg cagcagcggg gcccgagcac tgagggaagc10537
tgtacctcct tgcaaaggac tagaggttag aggagacccc ccgcaaacaa aaacagcata10597
ttgacgctgg gagagaccag agatcctgct gtctcctcag catcattcca ggcacagaac10657
gccagaaaat ggaatggtgc tgttgaatca acaggttcta gt 10699
<210> 8
<211> 3390
<212> PRT
<213> 3型登革病毒
<400> 8
Met Asn Asn Gln Arg Lys Lys Thr Gly Lys Pro Ser Ile Asn Met Leu
1 5 10 15
Lys Arg Val Arg Asn Arg Val Ser Thr Gly Ser Gln Leu Ala Lys Arg
20 25 30
Phe Ser Arg Gly Leu Leu Asn Gly Gln Gly Pro Met Lys Leu Val Met
35 40 45
Ala Phe Ile Ala Phe Leu Arg Phe Leu Ala Ile Pro Pro Thr Ala Gly
50 55 60
Val Leu Ala Arg Trp Gly Thr Phe Lys Lys Ser Gly Ala Ile Lys Val
65 70 75 80
Leu Lys Gly Phe Lys Lys Glu Ile Ser Asn Met Leu Ser Ile Ile Asn
85 90 95
Lys Arg Lys Lys Thr Ser Leu Cys Leu Met Met Met Leu Pro Ala Thr
100 105 110
Leu Ala Phe His Leu Thr Ser Arg Asp Gly Glu Pro Arg Met Ile Val
115 120 125
Gly Lys Asn Glu Arg Gly Lys Ser Leu Leu Phe Lys Thr Ala Ser Gly
130 135 140
Ile Asn Met Cys Thr Leu Ile Ala Met Asp Leu Gly Glu Met Cys Asp
145 150 155 160
Asp Thr Val Thr Tyr Lys Cys Pro His Ile Thr Glu Val Glu Pro Glu
165 170 175
Asp Ile Asp Cys Trp Cys Asn Leu Thr Ser Thr Trp Val Thr Tyr Gly
180 185 190
Thr Cys Asn Gln Ala Gly Glu His Arg Arg Asp Lys Arg Ser Val Ala
195 200 205
Leu Ala Pro His Val Gly Met Gly Leu Asp Thr Arg Thr Gln Thr Trp
210 215 220
Met Ser Ala Glu Gly Ala Trp Arg Gln Val Glu Lys Val Glu Thr Trp
225 230 235 240
Ala Leu Arg His Pro Gly Phe Thr Ile Leu Ala Leu Phe Leu Ala His
245 250 255
Tyr Ile Gly Thr Ser Leu Thr Gln Lys Val Val Ile Phe Ile Leu Leu
260 265 270
Met Leu Val Thr Pro Ser Met Thr Met Arg Cys Val Gly Val Gly Asn
275 280 285
Arg Asp Phe Val Glu Gly Leu Ser Gly Ala Thr Trp Val Asp Val Val
290 295 300
Leu Glu His Gly Gly Cys Val Thr Thr Met Ala Lys Asn Lys Pro Thr
305 310 315 320
Leu Asp Ile Glu Leu Gln Lys Thr Glu Ala Thr Gln Leu Ala Thr Leu
325 330 335
Arg Lys Leu Cys Ile Glu Gly Lys Ile Thr Asn Ile Thr Thr Asp Ser
340 345 350
Arg Cys Pro Thr Gln Gly Glu Ala Ile Leu Pro Glu Glu Gln Asp Gln
355 360 365
Asn Tyr Val Cys Lys His Thr Tyr Val Asp Arg Gly Trp Gly Asn Gly
370 375 380
Cys Gly Leu Phe Gly Lys Gly Ser Leu Val Thr Cys Ala Lys Phe Gln
385 390 395 400
Cys Leu Glu Ser Ile Glu Gly Lys Val Val Gln His Glu Asn Leu Lys
405 410 415
Tyr Thr Val Ile Ile Thr Val His Thr Gly Asp Gln His Gln Val Gly
420 425 430
Asn Glu Thr Gln Gly Val Thr Ala Glu Ile Thr Pro Gln Ala Ser Thr
435 440 445
Ala Glu Ala Ile Leu Pro Glu Tyr Gly Thr Leu Gly Leu Glu Cys Ser
450 455 460
Pro Arg Thr Gly Leu Asp Phe Asn Glu Met Ile Ser Leu Thr Met Lys
465 470 475 480
Asn Lys Ala Trp Met Val His Arg Gln Trp Phe Phe Asp Leu Pro Leu
485 490 495
Pro Trp Thr Ser Gly Ala Thr Ala Glu Thr Pro Thr Trp Asn Arg Lys
500 505 510
Glu Leu Leu Val Thr Phe Lys Asn Ala His Ala Lys Lys Gln Glu Val
515 520 525
Val Val Leu Gly Ser Gln Glu Gly Ala Met His Thr Ala Leu Thr Gly
530 535 540
Ala Thr Glu Ile Gln Thr Ser Gly Gly Thr Ser Ile Phe Ala Gly His
545 550 555 560
Leu Lys Cys Arg Leu Lys Met Asp Lys Leu Glu Leu Lys Gly Met Ser
565 570 575
Tyr Ala Met Cys Leu Ser Ser Phe Val Leu Lys Lys Glu Val Ser Glu
580 585 590
Thr Gln His Gly Thr Ile Leu Ile Lys Val Glu Tyr Lys Gly Glu Asp
595 600 605
Ala Pro Cys Lys Ile Pro Phe Ser Thr Glu Asp Gly Gln Gly Lys Ala
610 615 620
His Asn Gly Arg Leu Ile Thr Ala Asn Pro Val Val Thr Lys Lys Glu
625 630 635 640
Glu Pro Val Asn Ile Glu Ala Glu Pro Pro Phe Gly Glu Ser Asn Ile
645 650 655
Val Ile Gly Ile Gly Asp Lys Ala Leu Lys Ile Asn Trp Tyr Lys Lys
660 665 670
Gly Ser Ser Ile Gly Lys Met Phe Glu Ala Thr Ala Arg Gly Ala Arg
675 680 685
Arg Met Ala Ile Leu Gly Asp Thr Ala Trp Asp Phe Gly Ser Val Gly
690 695 700
Gly Val Leu Asn Ser Leu Gly Lys Met Val His Gln Ile Phe Gly Ser
705 710 715 720
Ala Tyr Thr Ala Leu Phe Gly Gly Val Ser Trp Met Met Lys Ile Gly
725 730 735
Ile Gly Val Leu Leu Thr Trp Ile Gly Leu Asn Ser Lys Asn Thr Ser
740 745 750
Met Ser Phe Ser Cys Ile Ala Ile Gly Ile Ile Thr Leu Tyr Leu Gly
755 760 765
Ala Val Val Gln Ala Asp Met Gly Cys Val Ile Asn Trp Lys Gly Lys
770 775 780
Glu Leu Lys Cys Gly Ser Gly Ile Phe Val Thr Asn Glu Val His Thr
785 790 795 800
Trp Thr Glu Gln Tyr Lys Phe Gln Ala Asp Ser Pro Lys Arg Leu Ala
805 810 815
Thr Ala Ile Ala Gly Ala Trp Glu Asn Gly Val Cys Gly Ile Arg Ser
820 825 830
Thr Thr Arg Met Glu Asn Leu Leu Trp Lys Gln Ile Ala Asn Glu Leu
835 840 845
Asn Tyr Ile Leu Trp Glu Asn Asn Ile Lys Leu Thr Val Val Val Gly
850 855 860
Asp Ile Thr Gly Val Leu Glu Gln Gly Lys Arg Thr Leu Thr Pro Gln
865 870 875 880
Pro Met Glu Leu Lys Tyr Ser Trp Lys Thr Trp Gly Lys Ala Lys Ile
885 890 895
Val Thr Ala Glu Thr Gln Asn Ser Ser Phe Ile Ile Asp Gly Pro Ser
900 905 910
Thr Pro Glu Cys Pro Ser Ala Ser Arg Ala Trp Asn Val Trp Glu Val
915 920 925
Glu Asp Tyr Gly Phe Gly Val Phe Thr Thr Asn Ile Trp Leu Lys Leu
930 935 940
Arg Glu Val Tyr Thr Gln Leu Cys Asp His Arg Leu Met Ser Ala Ala
945 950 955 960
Val Lys Asp Glu Arg Ala Val His Ala Asp Met Gly Tyr Trp Ile Glu
965 970 975
Ser Gln Lys Asn Gly Ser Trp Lys Leu Glu Lys Ala Ser Phe Ile Glu
980 985 990
Val Lys Thr Cys Thr Trp Pro Lys Ser His Thr Leu Trp Ser Asn Gly
995 1000 1005
Val Leu Glu Ser Asp Met Ile Ile Pro Lys Ser Leu Ala Gly Pro
1010 1015 1020
Ile Ser Gln His Asn His Arg Pro Gly Tyr His Thr Gln Thr Ala
1025 1030 1035
Gly Pro Trp His Leu Gly Lys Leu Glu Leu Asp Phe Asn Tyr Cys
1040 1045 1050
Glu Gly Thr Thr Val Val Ile Ser Glu Asn Cys Gly Thr Arg Gly
1055 1060 1065
Pro Ser Leu Arg Thr Thr Thr Val Ser Gly Lys Leu Ile His Glu
1070 1075 1080
Trp Cys Cys Arg Ser Cys Thr Leu Pro Pro Leu Arg Tyr Met Gly
1085 1090 1095
Glu Asp Gly Cys Trp Tyr Gly Met Glu Ile Arg Pro Ile Asn Glu
1100 1105 1110
Lys Glu Glu Asn Met Val Lys Ser Leu Ala Ser Ala Gly Ser Gly
1115 1120 1125
Lys Val Asp Asn Phe Thr Met Gly Val Leu Cys Leu Ala Ile Leu
1130 1135 1140
Phe Glu Glu Val Met Arg Gly Lys Phe Gly Lys Lys His Met Ile
1145 1150 1155
Ala Gly Val Leu Phe Thr Phe Val Leu Leu Leu Ser Gly Gln Ile
1160 1165 1170
Thr Trp Arg Asp Met Ala His Thr Leu Ile Met Ile Gly Ser Asn
1175 1180 1185
Ala Ser Asp Arg Met Gly Met Gly Val Thr Tyr Leu Ala Leu Ile
1190 1195 1200
Ala Thr Phe Lys Ile Gln Pro Phe Leu Ala Leu Gly Phe Phe Leu
1205 1210 1215
Arg Lys Leu Thr Ser Arg Glu Asn Leu Leu Leu Gly Val Gly Leu
1220 1225 1230
Ala Met Ala Ala Thr Leu Arg Leu Pro Glu Asp Ile Glu Gln Met
1235 1240 1245
Ala Asn Gly Ile Ala Leu Gly Leu Met Ala Leu Lys Leu Ile Thr
1250 1255 1260
Gln Phe Glu Thr Tyr Gln Leu Trp Thr Ala Leu Val Ser Leu Thr
1265 1270 1275
Cys Ser Asn Thr Ile Phe Thr Leu Thr Val Ala Trp Arg Thr Ala
1280 1285 1290
Thr Leu Ile Leu Ala Gly Ile Ser Leu Leu Pro Val Cys Gln Ser
1295 1300 1305
Ser Ser Met Arg Lys Thr Asp Trp Leu Pro Met Thr Val Ala Ala
1310 1315 1320
Met Gly Ala Gln Pro Leu Pro Leu Phe Ile Phe Ser Leu Lys Asp
1325 1330 1335
Thr Leu Lys Arg Arg Ser Trp Pro Leu Asn Glu Gly Val Met Ala
1340 1345 1350
Val Gly Leu Val Ser Ile Leu Ala Ser Ser Leu Leu Arg Asn Asp
1355 1360 1365
Val Pro Met Ala Gly Pro Leu Val Ala Gly Gly Leu Leu Ile Ala
1370 1375 1380
Cys Tyr Val Ile Thr Gly Thr Ser Ala Asp Leu Thr Val Glu Lys
1385 1390 1395
Ala Ala Asp Val Thr Trp Glu Glu Glu Ala Glu Gln Thr Gly Val
1400 1405 1410
Ser His Asn Leu Met Val Thr Val Asp Asp Asp Gly Thr Met Arg
1415 1420 1425
Ile Lys Asp Asp Glu Thr Glu Asn Ile Leu Thr Val Leu Leu Lys
1430 1435 1440
Thr Ala Leu Leu Ile Val Ser Gly Ile Phe Pro Tyr Ser Ile Pro
1445 1450 1455
Ala Thr Leu Leu Val Trp His Thr Trp Gln Lys Gln Thr Gln Arg
1460 1465 1470
Ser Gly Val Leu Trp Asp Val Pro Ser Pro Pro Glu Thr Gln Lys
1475 1480 1485
Ala Glu Leu Glu Glu Gly Val Tyr Arg Ile Lys Gln Gln Gly Ile
1490 1495 1500
Phe Gly Lys Thr Gln Val Gly Val Gly Val Gln Lys Glu Gly Val
1505 1510 1515
Phe His Thr Met Trp His Val Thr Arg Gly Ala Val Leu Thr His
1520 1525 1530
Asn Gly Lys Arg Leu Glu Pro Asn Trp Ala Ser Val Lys Lys Asp
1535 1540 1545
Leu Ile Ser Tyr Gly Gly Gly Trp Arg Leu Ser Ala Gln Trp Gln
1550 1555 1560
Lys Gly Glu Glu Val Gln Val Ile Ala Val Glu Pro Gly Lys Asn
1565 1570 1575
Pro Lys Asn Phe Gln Thr Met Pro Gly Ile Phe Gln Thr Thr Thr
1580 1585 1590
Gly Glu Ile Gly Ala Ile Ala Leu Asp Phe Lys Pro Gly Thr Ser
1595 1600 1605
Gly Ser Pro Ile Ile Asn Arg Glu Gly Lys Val Val Gly Leu Tyr
1610 1615 1620
Gly Asn Gly Val Val Thr Lys Asn Gly Gly Tyr Val Ser Gly Ile
1625 1630 1635
Ala Gln Thr Asn Ala Glu Pro Asp Gly Pro Thr Pro Glu Leu Glu
1640 1645 1650
Glu Glu Met Phe Lys Lys Arg Asn Leu Thr Ile Met Asp Leu His
1655 1660 1665
Pro Gly Ser Gly Lys Thr Arg Lys Tyr Leu Pro Ala Ile Val Arg
1670 1675 1680
Glu Ala Ile Lys Arg Arg Leu Arg Thr Leu Ile Leu Ala Pro Thr
1685 1690 1695
Arg Val Val Ala Ala Glu Met Glu Glu Ala Leu Lys Gly Leu Pro
1700 1705 1710
Ile Arg Tyr Gln Thr Thr Ala Thr Lys Ser Glu His Thr Gly Arg
1715 1720 1725
Glu Ile Val Asp Leu Met Cys His Ala Thr Phe Thr Met Arg Leu
1730 1735 1740
Leu Ser Pro Val Arg Val Pro Asn Tyr Asn Leu Ile Ile Met Asp
1745 1750 1755
Glu Ala His Phe Thr Asp Pro Ala Ser Ile Ala Ala Arg Gly Tyr
1760 1765 1770
Ile Ser Thr Arg Val Gly Met Gly Glu Ala Ala Ala Ile Phe Met
1775 1780 1785
Thr Ala Thr Pro Pro Gly Thr Ala Asp Ala Phe Pro Gln Ser Asn
1790 1795 1800
Ala Pro Ile Gln Asp Glu Glu Arg Asp Ile Pro Glu Arg Ser Trp
1805 1810 1815
Asn Ser Gly Asn Glu Trp Ile Thr Asp Phe Val Gly Lys Thr Val
1820 1825 1830
Trp Phe Val Pro Ser Ile Lys Ala Gly Asn Asp Ile Ala Asn Cys
1835 1840 1845
Leu Arg Lys Asn Gly Lys Lys Val Ile Gln Leu Ser Arg Lys Thr
1850 1855 1860
Phe Asp Thr Glu Tyr Gln Lys Thr Lys Leu Asn Asp Trp Asp Phe
1865 1870 1875
Val Val Thr Thr Asp Ile Ser Glu Met Gly Ala Asn Phe Lys Ala
1880 1885 1890
Asp Arg Val Ile Asp Pro Arg Arg Cys Leu Lys Pro Val Ile Leu
1895 1900 1905
Thr Asp Gly Pro Glu Arg Val Ile Leu Ala Gly Pro Met Pro Val
1910 1915 1920
Thr Val Ala Ser Ala Ala Gln Arg Arg Gly Arg Val Gly Arg Asn
1925 1930 1935
Pro Gln Lys Glu Asn Asp Gln Tyr Ile Phe Met Gly Gln Pro Leu
1940 1945 1950
Asn Asn Asp Glu Asp His Ala His Trp Thr Glu Ala Lys Met Leu
1955 1960 1965
Leu Asp Asn Ile Asn Thr Pro Glu Gly Ile Ile Pro Ala Leu Phe
1970 1975 1980
Glu Pro Glu Arg Glu Lys Ser Ala Ala Ile Asp Gly Glu Tyr Arg
1985 1990 1995
Leu Lys Gly Glu Ser Arg Lys Thr Phe Val Glu Leu Met Arg Arg
2000 2005 2010
Gly Asp Leu Pro Val Trp Leu Ala His Lys Val Ala Ser Glu Gly
2015 2020 2025
Ile Lys Tyr Thr Asp Arg Lys Trp Cys Phe Asp Gly Glu Arg Asn
2030 2035 2040
Asn Gln Ile Leu Glu Glu Asn Met Asp Val Glu Ile Trp Thr Lys
2045 2050 2055
Glu Gly Glu Lys Lys Lys Leu Arg Pro Arg Trp Leu Asp Ala Arg
2060 2065 2070
Thr Tyr Ser Asp Pro Leu Ala Leu Lys Glu Phe Lys Asp Phe Ala
2075 2080 2085
Ala Gly Arg Lys Ser Ile Ala Leu Asp Leu Val Thr Glu Ile Gly
2090 2095 2100
Arg Val Pro Ser His Leu Ala His Arg Thr Arg Asn Ala Leu Asp
2105 2110 2115
Asn Leu Val Met Leu His Thr Ser Glu His Gly Gly Arg Ala Tyr
2120 2125 2130
Arg His Ala Val Glu Glu Leu Pro Glu Thr Met Glu Thr Leu Leu
2135 2140 2145
Leu Leu Gly Leu Met Ile Leu Leu Thr Gly Gly Ala Met Leu Phe
2150 2155 2160
Leu Ile Ser Gly Lys Gly Ile Gly Lys Thr Ser Ile Gly Leu Ile
2165 2170 2175
Cys Val Ile Ala Ser Ser Gly Met Leu Trp Met Ala Asp Val Pro
2180 2185 2190
Leu Gln Trp Ile Ala Ser Ala Ile Val Leu Glu Phe Phe Met Met
2195 2200 2205
Val Leu Leu Ile Pro Glu Pro Glu Lys Gln Arg Thr Pro Gln Asp
2210 2215 2220
Asn Gln Leu Ala Tyr Val Val Ile Gly Ile Leu Thr Leu Ala Ala
2225 2230 2235
Ile Val Ala Ala Asn Glu Met Gly Leu Leu Glu Thr Thr Lys Arg
2240 2245 2250
Asp Leu Gly Met Ser Lys Glu Pro Gly Val Val Ser Pro Thr Ser
2255 2260 2265
Tyr Leu Asp Val Asp Leu His Pro Ala Ser Ala Trp Thr Leu Tyr
2270 2275 2280
Ala Val Ala Thr Thr Val Ile Thr Pro Met Leu Arg His Thr Ile
2285 2290 2295
Glu Asn Ser Thr Ala Asn Val Ser Leu Ala Ala Ile Ala Asn Gln
2300 2305 2310
Ala Val Val Leu Met Gly Leu Asp Lys Gly Trp Pro Ile Ser Lys
2315 2320 2325
Met Asp Leu Gly Val Pro Leu Leu Ala Leu Gly Cys Tyr Ser Gln
2330 2335 2340
Val Asn Pro Leu Thr Leu Ala Ala Ala Val Leu Leu Leu Val Thr
2345 2350 2355
His Tyr Ala Ile Ile Gly Pro Gly Leu Gln Ala Lys Ala Thr Arg
2360 2365 2370
Glu Ala Gln Lys Arg Thr Ala Ala Gly Ile Met Lys Asn Pro Thr
2375 2380 2385
Val Asp Gly Ile Met Thr Ile Asp Leu Asp Pro Val Ile Tyr Asp
2390 2395 2400
Ser Lys Phe Glu Lys Gln Leu Gly Gln Val Met Leu Leu Val Leu
2405 2410 2415
Cys Ala Val Gln Leu Leu Leu Met Arg Thr Ser Trp Ala Leu Cys
2420 2425 2430
Glu Val Leu Thr Leu Ala Thr Gly Pro Ile Thr Thr Leu Trp Glu
2435 2440 2445
Gly Ser Pro Gly Lys Phe Trp Asn Thr Thr Ile Ala Val Ser Met
2450 2455 2460
Ala Asn Ile Phe Arg Gly Ser Tyr Leu Ala Gly Ala Gly Leu Ala
2465 2470 2475
Phe Ser Ile Met Lys Ser Val Gly Thr Gly Lys Arg Gly Thr Gly
2480 2485 2490
Ser Gln Gly Glu Thr Leu Gly Glu Lys Trp Lys Lys Lys Leu Asn
2495 2500 2505
Gln Leu Ser Arg Lys Glu Phe Asp Leu Tyr Lys Lys Ser Gly Ile
2510 2515 2520
Thr Glu Val Asp Arg Thr Glu Ala Lys Glu Gly Leu Lys Arg Gly
2525 2530 2535
Glu Ile Thr His His Ala Val Ser Arg Gly Ser Ala Lys Leu Gln
2540 2545 2550
Trp Phe Val Glu Arg Asn Met Val Ile Pro Glu Gly Arg Val Ile
2555 2560 2565
Asp Leu Gly Cys Gly Arg Gly Gly Trp Ser Tyr Tyr Cys Ala Gly
2570 2575 2580
Leu Lys Lys Val Thr Glu Val Arg Gly Tyr Thr Lys Gly Gly Pro
2585 2590 2595
Gly His Glu Glu Pro Val Pro Met Ser Thr Tyr Gly Trp Asn Ile
2600 2605 2610
Val Lys Leu Met Ser Gly Lys Asp Val Phe Tyr Leu Pro Pro Glu
2615 2620 2625
Lys Cys Asp Thr Leu Leu Cys Asp Ile Gly Glu Ser Ser Pro Ser
2630 2635 2640
Pro Thr Val Glu Glu Ser Arg Thr Ile Arg Val Leu Lys Met Val
2645 2650 2655
Glu Pro Trp Leu Lys Asn Asn Gln Phe Cys Ile Lys Val Leu Asn
2660 2665 2670
Pro Tyr Met Pro Thr Val Ile Glu His Leu Glu Arg Leu Gln Arg
2675 2680 2685
Lys His Gly Gly Met Leu Val Arg Asn Pro Leu Ser Arg Asn Ser
2690 2695 2700
Thr His Glu Met Tyr Trp Ile Ser Asn Gly Thr Gly Asn Ile Val
2705 2710 2715
Ser Ser Val Asn Met Val Ser Arg Leu Leu Leu Asn Arg Phe Thr
2720 2725 2730
Met Thr His Arg Arg Pro Thr Ile Glu Lys Asp Val Asp Leu Gly
2735 2740 2745
Ala Gly Thr Arg His Val Asn Ala Glu Pro Glu Thr Pro Asn Met
2750 2755 2760
Asp Val Ile Gly Glu Arg Ile Lys Arg Ile Lys Glu Glu His Ser
2765 2770 2775
Ser Thr Trp His Tyr Asp Asp Glu Asn Pro Tyr Lys Thr Trp Ala
2780 2785 2790
Tyr His Gly Ser Tyr Glu Val Lys Ala Thr Gly Ser Ala Ser Ser
2795 2800 2805
Met Ile Asn Gly Val Val Lys Leu Leu Thr Lys Pro Trp Asp Val
2810 2815 2820
Val Pro Met Val Thr Gln Met Ala Met Thr Asp Thr Thr Pro Phe
2825 2830 2835
Gly Gln Gln Arg Val Phe Lys Glu Lys Val Asp Thr Arg Thr Pro
2840 2845 2850
Arg Pro Met Pro Gly Thr Arg Lys Val Met Glu Ile Thr Ala Glu
2855 2860 2865
Trp Leu Trp Arg Thr Leu Gly Arg Asn Lys Arg Pro Arg Leu Cys
2870 2875 2880
Thr Arg Glu Glu Phe Thr Lys Lys Val Arg Thr Asn Ala Ala Met
2885 2890 2895
Gly Ala Val Phe Thr Glu Glu Asn Gln Trp Asp Ser Ala Arg Ala
2900 2905 2910
Ala Val Glu Asp Glu Glu Phe Trp Lys Leu Val Asp Arg Glu Arg
2915 2920 2925
Glu Leu His Lys Leu Gly Lys Cys Gly Ser Cys Val Tyr Asn Met
2930 2935 2940
Met Gly Lys Arg Glu Lys Lys Leu Gly Glu Phe Gly Lys Ala Lys
2945 2950 2955
Gly Ser Arg Ala Ile Trp Tyr Met Trp Leu Gly Ala Arg Tyr Leu
2960 2965 2970
Glu Phe Glu Ala Leu Gly Phe Leu Asn Glu Asp His Trp Phe Ser
2975 2980 2985
Arg Glu Asn Ser Tyr Ser Gly Val Glu Gly Glu Gly Leu His Lys
2990 2995 3000
Leu Gly Tyr Ile Leu Arg Asp Ile Ser Lys Ile Pro Gly Gly Ala
3005 3010 3015
Met Tyr Ala Asp Asp Thr Ala Gly Trp Asp Thr Arg Ile Thr Glu
3020 3025 3030
Asp Asp Leu His Asn Glu Glu Lys Ile Thr Gln Gln Met Asp Pro
3035 3040 3045
Glu His Arg Gln Leu Ala Asn Ala Ile Phe Lys Leu Thr Tyr Gln
3050 3055 3060
Asn Lys Val Val Lys Val Gln Arg Pro Thr Pro Lys Gly Thr Val
3065 3070 3075
Met Asp Ile Ile Ser Arg Lys Asp Gln Arg Gly Ser Gly Gln Val
3080 3085 3090
Gly Thr Tyr Gly Leu Asn Thr Phe Thr Asn Met Glu Ala Gln Leu
3095 3100 3105
Ile Arg Gln Met Glu Gly Glu Gly Val Leu Ser Lys Ala Asp Leu
3110 3115 3120
Glu Asn Pro His Pro Leu Glu Lys Lys Ile Thr Gln Trp Leu Glu
3125 3130 3135
Thr Lys Gly Val Glu Arg Leu Lys Arg Met Ala Ile Ser Gly Asp
3140 3145 3150
Asp Cys Val Val Lys Pro Ile Asp Asp Arg Phe Ala Asn Ala Leu
3155 3160 3165
Leu Ala Leu Asn Asp Met Gly Lys Val Arg Lys Asp Ile Pro Gln
3170 3175 3180
Trp Gln Pro Ser Lys Gly Trp His Asp Trp Gln Gln Val Pro Phe
3185 3190 3195
Cys Ser His His Phe His Glu Leu Ile Met Lys Asp Gly Arg Lys
3200 3205 3210
Leu Val Val Pro Cys Arg Pro Gln Asp Glu Leu Ile Gly Arg Ala
3215 3220 3225
Arg Ile Ser Gln Gly Ala Gly Trp Ser Leu Arg Glu Thr Ala Cys
3230 3235 3240
Leu Gly Lys Ala Tyr Ala Gln Met Trp Ala Leu Met Tyr Phe His
3245 3250 3255
Arg Arg Asp Leu Arg Leu Ala Ser Asn Ala Ile Cys Ser Ala Val
3260 3265 3270
Pro Val His Trp Val Pro Thr Ser Arg Thr Thr Trp Ser Ile His
3275 3280 3285
Ala His His Gln Trp Met Thr Thr Glu Asp Met Leu Thr Val Trp
3290 3295 3300
Asn Arg Val Trp Ile Glu Asp Asn Pro Trp Met Glu Asp Lys Thr
3305 3310 3315
Pro Val Thr Thr Trp Glu Asp Val Pro Tyr Leu Gly Lys Arg Glu
3320 3325 3330
Asp Gln Trp Cys Gly Ser Leu Ile Gly Leu Thr Ser Arg Ala Thr
3335 3340 3345
Trp Ala Gln Asn Ile Leu Thr Ala Ile Gln Gln Val Arg Ser Leu
3350 3355 3360
Ile Gly Asn Glu Glu Phe Leu Asp Tyr Met Pro Ser Met Lys Arg
3365 3370 3375
Phe Arg Lys Glu Glu Glu Ser Glu Gly Ala Ile Trp
3380 3385 3390
<210> 9
<211> 10648
<212> DNA
<213> 4型登革病毒
<220>
<221> CDS
<222> (102)..(10265)
<400> 9
agttgttagt ctgtgtggac cgacaaggac agttccaaat cggaagcttg cttaacacag 60
ttctaacagt ttgtttgaat agagagcaga tctctggaaa a atg aac caa cga aaa 116
Met Asn Gln Arg Lys
1 5
aag gtg gtt aga cca cct ttc aat atg ctg aaa cgc gag aga aac cgc 164
Lys Val Val Arg Pro Pro Phe Asn Met Leu Lys Arg Glu Arg Asn Arg
10 15 20
gta tca acc cct caa ggg ttg gtg aag aga ttc tca acc gga ctt ttt 212
Val Ser Thr Pro Gln Gly Leu Val Lys Arg Phe Ser Thr Gly Leu Phe
25 30 35
tct ggg aaa gga ccc tta cgg atg gtg cta gca ttc atc acg ttt ttg 260
Ser Gly Lys Gly Pro Leu Arg Met Val Leu Ala Phe Ile Thr Phe Leu
40 45 50
cga gtc ctt tcc atc cca cca aca gca ggg att ctg aaa aga tgg gga 308
Arg Val Leu Ser Ile Pro Pro Thr Ala Gly Ile Leu Lys Arg Trp Gly
55 60 65
cag ttg aag aaa aat aag gcc atc agg ata ctg att gga ttc agg aag 356
Gln Leu Lys Lys Asn Lys Ala Ile Arg Ile Leu Ile Gly Phe Arg Lys
70 75 80 85
gag ata ggc cgc atg ctg aac atc ttg aac ggg aga aaa agg tca acg 404
Glu Ile Gly Arg Met Leu Asn Ile Leu Asn Gly Arg Lys Arg Ser Thr
90 95 100
ata aca ttg ctg tgc ttg att ccc acc gta atg gcg ttt cac ttg tca 452
Ile Thr Leu Leu Cys Leu Ile Pro Thr Val Met Ala Phe His Leu Ser
105 110 115
aca aga gat ggc gaa ccc ctc atg ata gtg gca aaa cat gaa agg ggg 500
Thr Arg Asp Gly Glu Pro Leu Met Ile Val Ala Lys His Glu Arg Gly
120 125 130
aga cct ctc ttg ttt aag aca aca gag ggg atc aac aaa tgc act ctc 548
Arg Pro Leu Leu Phe Lys Thr Thr Glu Gly Ile Asn Lys Cys Thr Leu
135 140 145
att gcc atg gac ttg ggt gaa atg tgt gag gac act gtc acg tat aaa 596
Ile Ala Met Asp Leu Gly Glu Met Cys Glu Asp Thr Val Thr Tyr Lys
150 155 160 165
tgc ccc tta ctg gtc aat acc gaa cct gaa gac att gat tgc tgg tgc 644
Cys Pro Leu Leu Val Asn Thr Glu Pro Glu Asp Ile Asp Cys Trp Cys
170 175 180
aat ctc acg tct acc tgg gtc atg tat ggg aca tgc acc cag agc gga 692
Asn Leu Thr Ser Thr Trp Val Met Tyr Gly Thr Cys Thr Gln Ser Gly
185 190 195
gaa cgg aga cga gag aag cgc tca gta gct tta aca cca cat tca gga 740
Glu Arg Arg Arg Glu Lys Arg Ser Val Ala Leu Thr Pro His Ser Gly
200 205 210
atg gga ttg gaa aca aga gct gag aca tgg atg tca tcg gaa ggg gct 788
Met Gly Leu Glu Thr Arg Ala Glu Thr Trp Met Ser Ser Glu Gly Ala
215 220 225
tgg aag cat gct cag aga gta gag agc tgg ata ctc aga aac cca gga 836
Trp Lys His Ala Gln Arg Val Glu Ser Trp Ile Leu Arg Asn Pro Gly
230 235 240 245
ttc gcg ctc ttg gca gga ttt atg gct tat atg att ggg caa aca gga 884
Phe Ala Leu Leu Ala Gly Phe Met Ala Tyr Met Ile Gly Gln Thr Gly
250 255 260
atc cag cga act gtc ttc ttt gtc cta atg atg ctg gtc gcc cca tcc 932
Ile Gln Arg Thr Val Phe Phe Val Leu Met Met Leu Val Ala Pro Ser
265 270 275
tac gga atg cga tgc gta gga gta gga aac aga gac ttt gtg gaa gga 980
Tyr Gly Met Arg Cys Val Gly Val Gly Asn Arg Asp Phe Val Glu Gly
280 285 290
gtc tca ggt gga gca tgg gtc gat ctg gtg cta gaa cat gga gga tgc 1028
Val Ser Gly Gly Ala Trp Val Asp Leu Val Leu Glu His Gly Gly Cys
295 300 305
gtc aca acc atg gcc cag gga aaa cca acc ttg gat ttt gaa ctg act 1076
Val Thr Thr Met Ala Gln Gly Lys Pro Thr Leu Asp Phe Glu Leu Thr
310 315 320 325
aag aca aca gcc aag gaa gtg gct ctg tta aga acc tat tgc att gaa 1124
Lys Thr Thr Ala Lys Glu Val Ala Leu Leu Arg Thr Tyr Cys Ile Glu
330 335 340
gcc tca ata tca aac ata acc acg gca aca aga tgt cca acg caa gga 1172
Ala Ser Ile Ser Asn Ile Thr Thr Ala Thr Arg Cys Pro Thr Gln Gly
345 350 355
gag cct tat cta aaa gag gaa caa gac caa cag tac att tgc cgg aga 1220
Glu Pro Tyr Leu Lys Glu Glu Gln Asp Gln Gln Tyr Ile Cys Arg Arg
360 365 370
gat gtg gta gac aga ggg tgg ggc aat ggc tgt ggc ttg ttt gga aaa 1268
Asp Val Val Asp Arg Gly Trp Gly Asn Gly Cys Gly Leu Phe Gly Lys
375 380 385
gga gga gtt gtg aca tgt gcg aag ttt tca tgt tcg ggg aag ata aca 1316
Gly Gly Val Val Thr Cys Ala Lys Phe Ser Cys Ser Gly Lys Ile Thr
390 395 400 405
ggc aat ttg gtc caa att gag aac ctt gaa tac aca gtg gtt gta aca 1364
Gly Asn Leu Val Gln Ile Glu Asn Leu Glu Tyr Thr Val Val Val Thr
410 415 420
gtc cac aat gga gac acc cat gca gta gga aat gac aca tcc aat cat 1412
Val His Asn Gly Asp Thr His Ala Val Gly Asn Asp Thr Ser Asn His
425 430 435
gga gtt aca gcc acg ata act ccc agg tca cca tcg gtg gaa gtc aaa 1460
Gly Val Thr Ala Thr Ile Thr Pro Arg Ser Pro Ser Val Glu Val Lys
440 445 450
ttg ccg gac tat gga gaa cta aca ctc gat tgt gaa ccc agg tct gga 1508
Leu Pro Asp Tyr Gly Glu Leu Thr Leu Asp Cys Glu Pro Arg Ser Gly
455 460 465
att gac ttt aat gag atg att ctg atg aaa atg aaa aag aaa aca tgg 1556
Ile Asp Phe Asn Glu Met Ile Leu Met Lys Met Lys Lys Lys Thr Trp
470 475 480 485
ctt gtg cat aag caa tgg ttt ttg gat cta cct cta cca tgg aca gca 1604
Leu Val His Lys Gln Trp Phe Leu Asp Leu Pro Leu Pro Trp Thr Ala
490 495 500
gga gca gac aca tca gag gtt cac tgg aat tac aaa gag aga atg gtg 1652
Gly Ala Asp Thr Ser Glu Val His Trp Asn Tyr Lys Glu Arg Met Val
505 510 515
aca ttt aag gtt cct cat gcc aag aga cag gat gtg aca gtg ctg gga 1700
Thr Phe Lys Val Pro His Ala Lys Arg Gln Asp Val Thr Val Leu Gly
520 525 530
tct cag gaa gga gcc atg cat tct gcc ctc gct gga gcc aca gaa gtg 1748
Ser Gln Glu Gly Ala Met His Ser Ala Leu Ala Gly Ala Thr Glu Val
535 540 545
gac tcc ggt gat gga aat cac atg ttt gca gga cat ctc aag tgc aaa 1796
Asp Ser Gly Asp Gly Asn His Met Phe Ala Gly His Leu Lys Cys Lys
550 555 560 565
gtc cgt atg gag aaa ttg aga atc aag gga atg tca tac acg atg tgt 1844
Val Arg Met Glu Lys Leu Arg Ile Lys Gly Met Ser Tyr Thr Met Cys
570 575 580
tca gga aag ttc tca att gac aaa gag atg gca gaa aca cag cat ggg 1892
Ser Gly Lys Phe Ser Ile Asp Lys Glu Met Ala Glu Thr Gln His Gly
585 590 595
aca aca gtg gtg aaa gtc aag tat gaa ggt gct gga gct ccg tgt aaa 1940
Thr Thr Val Val Lys Val Lys Tyr Glu Gly Ala Gly Ala Pro Cys Lys
600 605 610
gtc ccc ata gag ata aga gat gtg aac aag gaa aaa gtg gtt ggg cgt 1988
Val Pro Ile Glu Ile Arg Asp Val Asn Lys Glu Lys Val Val Gly Arg
615 620 625
atc atc tca tcc acc cct ttg gct gag aat acc aac agt gca acc aac 2036
Ile Ile Ser Ser Thr Pro Leu Ala Glu Asn Thr Asn Ser Ala Thr Asn
630 635 640 645
ata gag tta gaa ccc ccc ttt ggg gac agc tac ata gtg ata ggt gtt 2084
Ile Glu Leu Glu Pro Pro Phe Gly Asp Ser Tyr Ile Val Ile Gly Val
650 655 660
gga aac agt gca tta aca ctc cat tgg ttc agg aaa ggg agt tcc att 2132
Gly Asn Ser Ala Leu Thr Leu His Trp Phe Arg Lys Gly Ser Ser Ile
665 670 675
ggc aag atg ttt gag tcc aca tac aga ggt gca aaa cga atg gcc att 2180
Gly Lys Met Phe Glu Ser Thr Tyr Arg Gly Ala Lys Arg Met Ala Ile
680 685 690
cta ggt gaa aca gct tgg gat ttt ggt tcc gtt ggt gga ctg ttc aca 2228
Leu Gly Glu Thr Ala Trp Asp Phe Gly Ser Val Gly Gly Leu Phe Thr
695 700 705
tca ttg gga aag gct gtg cac cag gtt ttt gga agt gtg tat aca acc 2276
Ser Leu Gly Lys Ala Val His Gln Val Phe Gly Ser Val Tyr Thr Thr
710 715 720 725
atg ttt gga gga gtc tca tgg atg att aga atc cta att ggg ttc cta 2324
Met Phe Gly Gly Val Ser Trp Met Ile Arg Ile Leu Ile Gly Phe Leu
730 735 740
gtg ttg tgg att ggc acg aac tca agg aac act tca atg gct atg acg 2372
Val Leu Trp Ile Gly Thr Asn Ser Arg Asn Thr Ser Met Ala Met Thr
745 750 755
tgc ata gct gtt gga gga atc act ctg ttt ctg ggc ttc aca gtt caa 2420
Cys Ile Ala Val Gly Gly Ile Thr Leu Phe Leu Gly Phe Thr Val Gln
760 765 770
gca gac atg ggt tgt gtg gtg tca tgg agt ggg aaa gaa ttg aag tgt 2468
Ala Asp Met Gly Cys Val Val Ser Trp Ser Gly Lys Glu Leu Lys Cys
775 780 785
gga agc gga att ttt gtg gtt gac aac gtg cac act tgg aca gaa cag 2516
Gly Ser Gly Ile Phe Val Val Asp Asn Val His Thr Trp Thr Glu Gln
790 795 800 805
tac aaa ttt caa ccg gag tcc cca gcg aga cta gcg tct gca ata ttg 2564
Tyr Lys Phe Gln Pro Glu Ser Pro Ala Arg Leu Ala Ser Ala Ile Leu
810 815 820
aat gcc cac aaa gat ggg gtc tgt gga att aga tca acc acg agg ctg 2612
Asn Ala His Lys Asp Gly Val Cys Gly Ile Arg Ser Thr Thr Arg Leu
825 830 835
gaa aat gtc atg tgg aag caa ata acc aac gag cta aat tat gtt ctc 2660
Glu Asn Val Met Trp Lys Gln Ile Thr Asn Glu Leu Asn Tyr Val Leu
840 845 850
tgg gaa gga gga cat gac ctc act gta gtg gct ggg gat gtg aag ggg 2708
Trp Glu Gly Gly His Asp Leu Thr Val Val Ala Gly Asp Val Lys Gly
855 860 865
gtg ttg acc aaa ggc aag aga gca ctc aca ccc cca gtg aat gat ctg 2756
Val Leu Thr Lys Gly Lys Arg Ala Leu Thr Pro Pro Val Asn Asp Leu
870 875 880 885
aaa tat tca tgg aag aca tgg gga aaa gca aaa atc ttc acc cca gaa 2804
Lys Tyr Ser Trp Lys Thr Trp Gly Lys Ala Lys Ile Phe Thr Pro Glu
890 895 900
gca aga aat agc aca ttt tta ata gac gga cca gac acc tcc gaa tgc 2852
Ala Arg Asn Ser Thr Phe Leu Ile Asp Gly Pro Asp Thr Ser Glu Cys
905 910 915
ccc aat gaa cga aga gca tgg aac ttt ctt gag gtg gaa gac tat gga 2900
Pro Asn Glu Arg Arg Ala Trp Asn Phe Leu Glu Val Glu Asp Tyr Gly
920 925 930
ttt ggc atg ttc acg acc aac ata tgg atg aaa ttc cga gaa gga agt 2948
Phe Gly Met Phe Thr Thr Asn Ile Trp Met Lys Phe Arg Glu Gly Ser
935 940 945
tca gaa gtg tgt gac cac agg tta atg tca gcg gca att aaa gat cag 2996
Ser Glu Val Cys Asp His Arg Leu Met Ser Ala Ala Ile Lys Asp Gln
950 955 960 965
aaa gct gtg cat gct gac atg ggt tat tgg ata gag agc tca aaa aac 3044
Lys Ala Val His Ala Asp Met Gly Tyr Trp Ile Glu Ser Ser Lys Asn
970 975 980
cag acc tgg cag ata gag aaa gca tct ctt att gaa gtg aaa aca tgt 3092
Gln Thr Trp Gln Ile Glu Lys Ala Ser Leu Ile Glu Val Lys Thr Cys
985 990 995
ctg tgg ccc aag acc cac aca ttg tgg agc aat gga gtg ctg gaa 3137
Leu Trp Pro Lys Thr His Thr Leu Trp Ser Asn Gly Val Leu Glu
1000 1005 1010
agc cag atg ctc att cca aaa tca tat gcg ggc cct ttt tca cag 3182
Ser Gln Met Leu Ile Pro Lys Ser Tyr Ala Gly Pro Phe Ser Gln
1015 1020 1025
cac aat tac cgc cag ggc tat gcc acg caa acc gtg ggc cca tgg 3227
His Asn Tyr Arg Gln Gly Tyr Ala Thr Gln Thr Val Gly Pro Trp
1030 1035 1040
cac tta ggc aaa tta gag ata gac ttt gga gaa tgc ccc gga aca 3272
His Leu Gly Lys Leu Glu Ile Asp Phe Gly Glu Cys Pro Gly Thr
1045 1050 1055
aca gtc gca att cag gag gat tgt gac cat aga ggc cca tct ttg 3317
Thr Val Ala Ile Gln Glu Asp Cys Asp His Arg Gly Pro Ser Leu
1060 1065 1070
agg acc acc act gca tct gga aaa cta gtc acg caa tgg tgc tgc 3362
Arg Thr Thr Thr Ala Ser Gly Lys Leu Val Thr Gln Trp Cys Cys
1075 1080 1085
cgc tcc tgc acg atg cct ccc tta agg ttc ttg gga gaa gat ggg 3407
Arg Ser Cys Thr Met Pro Pro Leu Arg Phe Leu Gly Glu Asp Gly
1090 1095 1100
tgc tgg tat ggg atg gag att agg ccc ttg agt gaa aaa gaa gag 3452
Cys Trp Tyr Gly Met Glu Ile Arg Pro Leu Ser Glu Lys Glu Glu
1105 1110 1115
aac atg gtc aaa tca cag gta acg gcc gga cag ggc aca tca gaa 3497
Asn Met Val Lys Ser Gln Val Thr Ala Gly Gln Gly Thr Ser Glu
1120 1125 1130
act ttt tct atg ggt ctg ttg tgc ctg acc ttg ttt gtg gaa gaa 3542
Thr Phe Ser Met Gly Leu Leu Cys Leu Thr Leu Phe Val Glu Glu
1135 1140 1145
tgc ttg agg aga aga gtc act agg aaa cac atg ata ttg gtt gtg 3587
Cys Leu Arg Arg Arg Val Thr Arg Lys His Met Ile Leu Val Val
1150 1155 1160
gtg atc act ctt tgt gcc atc atc cta gga ggc ctc aca tgg atg 3632
Val Ile Thr Leu Cys Ala Ile Ile Leu Gly Gly Leu Thr Trp Met
1165 1170 1175
gac tta cta cga gcc ctc atc atg ttg ggg gac act atg tct ggt 3677
Asp Leu Leu Arg Ala Leu Ile Met Leu Gly Asp Thr Met Ser Gly
1180 1185 1190
aga ata gga gga cag atc cac cta gcc atc atg gca gtg ttc aag 3722
Arg Ile Gly Gly Gln Ile His Leu Ala Ile Met Ala Val Phe Lys
1195 1200 1205
atg tca cca gga tac gtg ctg ggt gtg ttt tta agg aaa ctc act 3767
Met Ser Pro Gly Tyr Val Leu Gly Val Phe Leu Arg Lys Leu Thr
1210 1215 1220
tca aga gag aca gca cta atg gta ata gga atg gcc atg aca acg 3812
Ser Arg Glu Thr Ala Leu Met Val Ile Gly Met Ala Met Thr Thr
1225 1230 1235
gtg ctt tca att cca cat gac ctt atg gaa ctc att gat gga ata 3857
Val Leu Ser Ile Pro His Asp Leu Met Glu Leu Ile Asp Gly Ile
1240 1245 1250
tca ctg ggg cta att ttg cta aaa ata gtg aca cat ttt gac aac 3902
Ser Leu Gly Leu Ile Leu Leu Lys Ile Val Thr His Phe Asp Asn
1255 1260 1265
acc caa gtg gga acc tta gcc ctt tcc ttg acc ttc ata aga tca 3947
Thr Gln Val Gly Thr Leu Ala Leu Ser Leu Thr Phe Ile Arg Ser
1270 1275 1280
aca atg cca ttg gtc atg gct tgg agg acc att atg gct gtg ttg 3992
Thr Met Pro Leu Val Met Ala Trp Arg Thr Ile Met Ala Val Leu
1285 1290 1295
ttt gtg gtc aca ctc att cct ttg tgc agg aca agc tgt ctt caa 4037
Phe Val Val Thr Leu Ile Pro Leu Cys Arg Thr Ser Cys Leu Gln
1300 1305 1310
aaa cag tct cat tgg gta gaa ata aca gca ctc atc cta gga gcc 4082
Lys Gln Ser His Trp Val Glu Ile Thr Ala Leu Ile Leu Gly Ala
1315 1320 1325
caa gct ctg cca gtg tac cta atg act ctt atg aaa gga gcc tca 4127
Gln Ala Leu Pro Val Tyr Leu Met Thr Leu Met Lys Gly Ala Ser
1330 1335 1340
aga aga tct tgg cct ctt aac gag ggc ata atg gct gtg ggt ttg 4172
Arg Arg Ser Trp Pro Leu Asn Glu Gly Ile Met Ala Val Gly Leu
1345 1350 1355
gtt agt ctc tta gga agc gct ctt tta aag aat gat gtc cct tta 4217
Val Ser Leu Leu Gly Ser Ala Leu Leu Lys Asn Asp Val Pro Leu
1360 1365 1370
gct ggc cca atg gtg gca gga ggc tta ctt ctg gcg gct tac gtg 4262
Ala Gly Pro Met Val Ala Gly Gly Leu Leu Leu Ala Ala Tyr Val
1375 1380 1385
atg agt ggt agc tca gca gat ctg tca cta gag aag gcc gcc aat 4307
Met Ser Gly Ser Ser Ala Asp Leu Ser Leu Glu Lys Ala Ala Asn
1390 1395 1400
gtg cag tgg gat gaa atg gca gac ata aca ggc tca agc cca atc 4352
Val Gln Trp Asp Glu Met Ala Asp Ile Thr Gly Ser Ser Pro Ile
1405 1410 1415
ata gaa gtg aag cag gat gaa gat ggc tct ttc tcc ata cgg gac 4397
Ile Glu Val Lys Gln Asp Glu Asp Gly Ser Phe Ser Ile Arg Asp
1420 1425 1430
gtc gag gaa acc aat atg ata acc ctt ttg gtg aaa ctg gca ctg 4442
Val Glu Glu Thr Asn Met Ile Thr Leu Leu Val Lys Leu Ala Leu
1435 1440 1445
ata aca gtg tca ggt ctc tac ccc ttg gca att cca gtc aca atg 4487
Ile Thr Val Ser Gly Leu Tyr Pro Leu Ala Ile Pro Val Thr Met
1450 1455 1460
acc tta tgg tac atg tgg caa gtg aaa aca caa aga tca gga gcc 4532
Thr Leu Trp Tyr Met Trp Gln Val Lys Thr Gln Arg Ser Gly Ala
1465 1470 1475
ctg tgg gac gtc ccc tca ccc gct gcc act caa aaa gcc gca ctg 4577
Leu Trp Asp Val Pro Ser Pro Ala Ala Thr Gln Lys Ala Ala Leu
1480 1485 1490
tct gaa gga gtg tac agg atc atg caa aga ggg tta ttt ggg aaa 4622
Ser Glu Gly Val Tyr Arg Ile Met Gln Arg Gly Leu Phe Gly Lys
1495 1500 1505
act cag gtt gga gta ggg ata cac atg gaa ggt gta ttt cac aca 4667
Thr Gln Val Gly Val Gly Ile His Met Glu Gly Val Phe His Thr
1510 1515 1520
atg tgg cat gta aca aga gga tca gtg atc tgc cat gag act ggg 4712
Met Trp His Val Thr Arg Gly Ser Val Ile Cys His Glu Thr Gly
1525 1530 1535
aga ttg gag cca tct tgg gct gac gtc agg aat gac atg ata tca 4757
Arg Leu Glu Pro Ser Trp Ala Asp Val Arg Asn Asp Met Ile Ser
1540 1545 1550
tac ggt ggg gga tgg aga ctt gga gac aaa tgg gac aaa gaa gaa 4802
Tyr Gly Gly Gly Trp Arg Leu Gly Asp Lys Trp Asp Lys Glu Glu
1555 1560 1565
gat gtt cag gtc ctc gcc ata gaa cca gga aaa aat cct aaa cat 4847
Asp Val Gln Val Leu Ala Ile Glu Pro Gly Lys Asn Pro Lys His
1570 1575 1580
gtc caa acg aaa ccc ggc ctt ttc aag acc cta act gga gaa att 4892
Val Gln Thr Lys Pro Gly Leu Phe Lys Thr Leu Thr Gly Glu Ile
1585 1590 1595
gga gca gta aca tta gat ttc aaa ccc gga acg tct ggt tct ccc 4937
Gly Ala Val Thr Leu Asp Phe Lys Pro Gly Thr Ser Gly Ser Pro
1600 1605 1610
atc atc aac agg aaa gga aaa gtc atc gga ctc tat gga aat gga 4982
Ile Ile Asn Arg Lys Gly Lys Val Ile Gly Leu Tyr Gly Asn Gly
1615 1620 1625
gta gtt acc aaa tca ggt gat tac gtc agt gcc ata acg caa gcc 5027
Val Val Thr Lys Ser Gly Asp Tyr Val Ser Ala Ile Thr Gln Ala
1630 1635 1640
gaa aga att gga gag cca gat tat gaa gtg gat gag gac att ttt 5072
Glu Arg Ile Gly Glu Pro Asp Tyr Glu Val Asp Glu Asp Ile Phe
1645 1650 1655
cga aag aaa aga tta act ata atg gac tta cac ccc gga gct gga 5117
Arg Lys Lys Arg Leu Thr Ile Met Asp Leu His Pro Gly Ala Gly
1660 1665 1670
aag aca aaa aga att ctt cca tca ata gtg aga gaa gcc tta aaa 5162
Lys Thr Lys Arg Ile Leu Pro Ser Ile Val Arg Glu Ala Leu Lys
1675 1680 1685
agg agg ctg cga acc ttg att ttg gct ccc acg aga gtg gtg gcg 5207
Arg Arg Leu Arg Thr Leu Ile Leu Ala Pro Thr Arg Val Val Ala
1690 1695 1700
gcc gag atg gaa gag gcc cta cgt gga ctg cca atc cgt tat cag 5252
Ala Glu Met Glu Glu Ala Leu Arg Gly Leu Pro Ile Arg Tyr Gln
1705 1710 1715
acc cca gct gtg aaa tca gaa cac aca gga aga gag att gta gac 5297
Thr Pro Ala Val Lys Ser Glu His Thr Gly Arg Glu Ile Val Asp
1720 1725 1730
ctc atg tgt cat gca acc ttc aca aca aga ctt ttg tca tca acc 5342
Leu Met Cys His Ala Thr Phe Thr Thr Arg Leu Leu Ser Ser Thr
1735 1740 1745
aga gtt cca aat tac aac ctc ata gtg atg gat gaa gca cat ttc 5387
Arg Val Pro Asn Tyr Asn Leu Ile Val Met Asp Glu Ala His Phe
1750 1755 1760
acc gat cct tct agt gtc gcg gct aga gga tac atc tcg acc agg 5432
Thr Asp Pro Ser Ser Val Ala Ala Arg Gly Tyr Ile Ser Thr Arg
1765 1770 1775
gtg gaa atg gga gag gca gca gcc atc ttc atg acc gca acc cct 5477
Val Glu Met Gly Glu Ala Ala Ala Ile Phe Met Thr Ala Thr Pro
1780 1785 1790
ccc gga gcg aca gat ccc ttt ccc cag agc aac agc cca ata gaa 5522
Pro Gly Ala Thr Asp Pro Phe Pro Gln Ser Asn Ser Pro Ile Glu
1795 1800 1805
gac atc gag agg gaa att ccg gaa agg tca tgg aac aca ggg ttc 5567
Asp Ile Glu Arg Glu Ile Pro Glu Arg Ser Trp Asn Thr Gly Phe
1810 1815 1820
gac tgg ata aca gac tac caa ggg aaa act gtg tgg ttt gtt ccc 5612
Asp Trp Ile Thr Asp Tyr Gln Gly Lys Thr Val Trp Phe Val Pro
1825 1830 1835
agc ata aaa gct gga aat gac att gca aat tgt ttg aga aag tcg 5657
Ser Ile Lys Ala Gly Asn Asp Ile Ala Asn Cys Leu Arg Lys Ser
1840 1845 1850
gga aag aaa gtt atc cag ttg agt agg aaa acc ttt gat aca gag 5702
Gly Lys Lys Val Ile Gln Leu Ser Arg Lys Thr Phe Asp Thr Glu
1855 1860 1865
tat cca aaa acg aaa ctc acg gac tgg gat ttt gtg gtc act aca 5747
Tyr Pro Lys Thr Lys Leu Thr Asp Trp Asp Phe Val Val Thr Thr
1870 1875 1880
gac ata tct gaa atg ggg gcc aat ttt aga gct ggg aga gtg ata 5792
Asp Ile Ser Glu Met Gly Ala Asn Phe Arg Ala Gly Arg Val Ile
1885 1890 1895
gac cct agg aga tgc ctc aag cca gtt atc cta aca gat ggg cca 5837
Asp Pro Arg Arg Cys Leu Lys Pro Val Ile Leu Thr Asp Gly Pro
1900 1905 1910
gag aga gtc att tta gca ggt cct att cca gtg act cca gca agc 5882
Glu Arg Val Ile Leu Ala Gly Pro Ile Pro Val Thr Pro Ala Ser
1915 1920 1925
gct gct cag aga aga ggg cga ata gga agg aac cca gca caa gaa 5927
Ala Ala Gln Arg Arg Gly Arg Ile Gly Arg Asn Pro Ala Gln Glu
1930 1935 1940
gac gac caa tac gtt ttc tcc gga gac cca cta aaa aat gat gaa 5972
Asp Asp Gln Tyr Val Phe Ser Gly Asp Pro Leu Lys Asn Asp Glu
1945 1950 1955
gat cat gcc cac tgg aca gaa gca aag atg ctg ctt gac aat atc 6017
Asp His Ala His Trp Thr Glu Ala Lys Met Leu Leu Asp Asn Ile
1960 1965 1970
tac acc cca gaa ggg atc att cca aca ttg ttt ggt ccg gaa agg 6062
Tyr Thr Pro Glu Gly Ile Ile Pro Thr Leu Phe Gly Pro Glu Arg
1975 1980 1985
gaa aaa acc caa gcc att gat gga gag ttt cgc ctc aga ggg gaa 6107
Glu Lys Thr Gln Ala Ile Asp Gly Glu Phe Arg Leu Arg Gly Glu
1990 1995 2000
caa agg aag act ttt gtg gaa tta atg agg aga gga gac ctt ccg 6152
Gln Arg Lys Thr Phe Val Glu Leu Met Arg Arg Gly Asp Leu Pro
2005 2010 2015
gtg tgg ctg agc tat aag gta gct tct gct ggc att tct tac aaa 6197
Val Trp Leu Ser Tyr Lys Val Ala Ser Ala Gly Ile Ser Tyr Lys
2020 2025 2030
gat cgg gaa tgg tgc ttc aca ggg gaa agg aat aac caa att tta 6242
Asp Arg Glu Trp Cys Phe Thr Gly Glu Arg Asn Asn Gln Ile Leu
2035 2040 2045
gaa gaa aac atg gag gtt gaa att tgg act aga gag gga gaa aag 6287
Glu Glu Asn Met Glu Val Glu Ile Trp Thr Arg Glu Gly Glu Lys
2050 2055 2060
aaa aag cta agg cca aga tgg tta gat gca cgt gta tac gct gac 6332
Lys Lys Leu Arg Pro Arg Trp Leu Asp Ala Arg Val Tyr Ala Asp
2065 2070 2075
ccc atg gct ttg aag gat ttt aag gag ttt gct agt gga agg aag 6377
Pro Met Ala Leu Lys Asp Phe Lys Glu Phe Ala Ser Gly Arg Lys
2080 2085 2090
agc ata act ctc gac atc cta aca gag att gcc agt ttg cca act 6422
Ser Ile Thr Leu Asp Ile Leu Thr Glu Ile Ala Ser Leu Pro Thr
2095 2100 2105
tac ctt tcc tct agg gcc aag ctc gcc ctt gat aac ata gtc atg 6467
Tyr Leu Ser Ser Arg Ala Lys Leu Ala Leu Asp Asn Ile Val Met
2110 2115 2120
ctc cac aca aca gaa aga gga ggg agg gcc tac caa cac gcc ctg 6512
Leu His Thr Thr Glu Arg Gly Gly Arg Ala Tyr Gln His Ala Leu
2125 2130 2135
aac gaa ctc ccg gag tca ctg gaa aca ctt atg ctt gta gct tta 6557
Asn Glu Leu Pro Glu Ser Leu Glu Thr Leu Met Leu Val Ala Leu
2140 2145 2150
cta ggt gct atg aca gca ggt atc ttc ctg ttt ttc atg caa ggg 6602
Leu Gly Ala Met Thr Ala Gly Ile Phe Leu Phe Phe Met Gln Gly
2155 2160 2165
aaa gga ata ggg aaa ttg tca atg ggt ttg ata acc att gcg gtg 6647
Lys Gly Ile Gly Lys Leu Ser Met Gly Leu Ile Thr Ile Ala Val
2170 2175 2180
gct agt ggc ttg ctc tgg gta gca gaa att caa ccc cag tgg ata 6692
Ala Ser Gly Leu Leu Trp Val Ala Glu Ile Gln Pro Gln Trp Ile
2185 2190 2195
gcg gcc tca atc ata cta gag ttt ttt ctc atg gta ctg ttg ata 6737
Ala Ala Ser Ile Ile Leu Glu Phe Phe Leu Met Val Leu Leu Ile
2200 2205 2210
ccg gaa cca gaa aaa caa agg acc cca caa gac aat caa ttg atc 6782
Pro Glu Pro Glu Lys Gln Arg Thr Pro Gln Asp Asn Gln Leu Ile
2215 2220 2225
tac gtc ata ttg acc att ctc acc att att ggt ctc ata gca gcc 6827
Tyr Val Ile Leu Thr Ile Leu Thr Ile Ile Gly Leu Ile Ala Ala
2230 2235 2240
aac gag atg ggg ctg att gaa aaa aca aaa acg gat ttt ggg ttt 6872
Asn Glu Met Gly Leu Ile Glu Lys Thr Lys Thr Asp Phe Gly Phe
2245 2250 2255
tac cag gta aaa aca gaa acc acc atc ctc gat gtg gac ttg aga 6917
Tyr Gln Val Lys Thr Glu Thr Thr Ile Leu Asp Val Asp Leu Arg
2260 2265 2270
cca gct tca gca tgg acg ctc tat gca gta gcc acc aca att ctg 6962
Pro Ala Ser Ala Trp Thr Leu Tyr Ala Val Ala Thr Thr Ile Leu
2275 2280 2285
act ccc atg ctg aga cac acc ata gaa aac acg tcg gcc aac cta 7007
Thr Pro Met Leu Arg His Thr Ile Glu Asn Thr Ser Ala Asn Leu
2290 2295 2300
tct cta gca gcc att gcc aac cag gcg gcc gtc cta atg ggg ctt 7052
Ser Leu Ala Ala Ile Ala Asn Gln Ala Ala Val Leu Met Gly Leu
2305 2310 2315
gga aaa gga tgg ccg ctc cac aga atg gac ctc ggt gtg ccg ctg 7097
Gly Lys Gly Trp Pro Leu His Arg Met Asp Leu Gly Val Pro Leu
2320 2325 2330
tta gca atg gga tgc tat tct caa gtg aac cca aca act ttg aca 7142
Leu Ala Met Gly Cys Tyr Ser Gln Val Asn Pro Thr Thr Leu Thr
2335 2340 2345
gca tcc tta gtc atg ctt tta gtc cat tat gca ata ata ggt cca 7187
Ala Ser Leu Val Met Leu Leu Val His Tyr Ala Ile Ile Gly Pro
2350 2355 2360
gga ttg cag gca aaa gcc aca aga gag gcc cag aaa agg aca gct 7232
Gly Leu Gln Ala Lys Ala Thr Arg Glu Ala Gln Lys Arg Thr Ala
2365 2370 2375
gct ggg atc atg aaa aac ccc acg gtg gac ggg ata aca gta ata 7277
Ala Gly Ile Met Lys Asn Pro Thr Val Asp Gly Ile Thr Val Ile
2380 2385 2390
gat cta gaa cca ata tcc tat gac cca aaa ttt gaa aag caa tta 7322
Asp Leu Glu Pro Ile Ser Tyr Asp Pro Lys Phe Glu Lys Gln Leu
2395 2400 2405
ggg cag gtc atg cta ctc gtc ttg tgt gct gga caa cta ctc ttg 7367
Gly Gln Val Met Leu Leu Val Leu Cys Ala Gly Gln Leu Leu Leu
2410 2415 2420
atg aga aca aca tgg gct ttc tgt gaa gtc ttg act ttg gcc aca 7412
Met Arg Thr Thr Trp Ala Phe Cys Glu Val Leu Thr Leu Ala Thr
2425 2430 2435
gga cca atc ttg acc ttg tgg gag ggc aac ccg gga agg ttt tgg 7457
Gly Pro Ile Leu Thr Leu Trp Glu Gly Asn Pro Gly Arg Phe Trp
2440 2445 2450
aac acg acc ata gcc gta tcc acc gcc aac att ttc agg gga agt 7502
Asn Thr Thr Ile Ala Val Ser Thr Ala Asn Ile Phe Arg Gly Ser
2455 2460 2465
tac ctg gcg gga gct gga ctg gct ttt tca ctc ata aag aat gca 7547
Tyr Leu Ala Gly Ala Gly Leu Ala Phe Ser Leu Ile Lys Asn Ala
2470 2475 2480
caa acc cct agg agg gga act ggg acc aca gga gag aca ctg gga 7592
Gln Thr Pro Arg Arg Gly Thr Gly Thr Thr Gly Glu Thr Leu Gly
2485 2490 2495
gag aag tgg aag aga cag cta aac tca tta gac aga aaa gag ttt 7637
Glu Lys Trp Lys Arg Gln Leu Asn Ser Leu Asp Arg Lys Glu Phe
2500 2505 2510
gaa gag tat aaa aga agt gga ata cta gaa gtg gac agg act gaa 7682
Glu Glu Tyr Lys Arg Ser Gly Ile Leu Glu Val Asp Arg Thr Glu
2515 2520 2525
gcc aag tct gcc ctg aaa gat ggg tct aaa atc aag cat gca gta 7727
Ala Lys Ser Ala Leu Lys Asp Gly Ser Lys Ile Lys His Ala Val
2530 2535 2540
tct aga ggg tcc agt aag att aga tgg att gtt gag aga ggg atg 7772
Ser Arg Gly Ser Ser Lys Ile Arg Trp Ile Val Glu Arg Gly Met
2545 2550 2555
gta aag cca aaa ggg aaa gtt gta gat ctt ggc tgt ggg aga gga 7817
Val Lys Pro Lys Gly Lys Val Val Asp Leu Gly Cys Gly Arg Gly
2560 2565 2570
gga tgg tct tat tac atg gcg acg ctc aag aac gtg act gaa gtg 7862
Gly Trp Ser Tyr Tyr Met Ala Thr Leu Lys Asn Val Thr Glu Val
2575 2580 2585
aaa ggg tat aca aaa gga ggt cca gga cat gaa gaa ccg att ccc 7907
Lys Gly Tyr Thr Lys Gly Gly Pro Gly His Glu Glu Pro Ile Pro
2590 2595 2600
atg gct act tat ggc tgg aat ttg gtc aaa ctc cat tca ggg gtt 7952
Met Ala Thr Tyr Gly Trp Asn Leu Val Lys Leu His Ser Gly Val
2605 2610 2615
gac gtg ttc tac aaa ccc aca gag caa gtg gac acc ctg ctc tgt 7997
Asp Val Phe Tyr Lys Pro Thr Glu Gln Val Asp Thr Leu Leu Cys
2620 2625 2630
gat att ggg gag tca tct tct aat cca aca ata gag gaa gga aga 8042
Asp Ile Gly Glu Ser Ser Ser Asn Pro Thr Ile Glu Glu Gly Arg
2635 2640 2645
aca tta aga gtt ttg aag atg gtg gag cca tgg ctc tct tca aaa 8087
Thr Leu Arg Val Leu Lys Met Val Glu Pro Trp Leu Ser Ser Lys
2650 2655 2660
cct gaa ttc tgc atc aaa gtc ctt aac ccc tac atg cca aca gtc 8132
Pro Glu Phe Cys Ile Lys Val Leu Asn Pro Tyr Met Pro Thr Val
2665 2670 2675
ata gaa gag ctg gag aaa ctg cag aga aaa cat ggt ggg aac ctt 8177
Ile Glu Glu Leu Glu Lys Leu Gln Arg Lys His Gly Gly Asn Leu
2680 2685 2690
gtc aga tgc ccg ctg tcc agg aac tcc acc cat gag atg tat tgg 8222
Val Arg Cys Pro Leu Ser Arg Asn Ser Thr His Glu Met Tyr Trp
2695 2700 2705
gtg tca gga gcg tcg gga aac att gtg agc tct gtg aac aca aca 8267
Val Ser Gly Ala Ser Gly Asn Ile Val Ser Ser Val Asn Thr Thr
2710 2715 2720
tca aag atg ttg ttg aac agg ttc aca aca agg cat agg aaa ccc 8312
Ser Lys Met Leu Leu Asn Arg Phe Thr Thr Arg His Arg Lys Pro
2725 2730 2735
act tat gag aag gac gta gat ctt ggg gca gga acg aga agt gtc 8357
Thr Tyr Glu Lys Asp Val Asp Leu Gly Ala Gly Thr Arg Ser Val
2740 2745 2750
tcc act gaa aca gaa aaa cca gac atg aca att att ggg aga agg 8402
Ser Thr Glu Thr Glu Lys Pro Asp Met Thr Ile Ile Gly Arg Arg
2755 2760 2765
ctt cag cga ttg caa gag gag cac aaa gaa acc tgg cat tat gat 8447
Leu Gln Arg Leu Gln Glu Glu His Lys Glu Thr Trp His Tyr Asp
2770 2775 2780
cag gaa aac cca tac aga acc tgg gcg tat cat gga agc tat gaa 8492
Gln Glu Asn Pro Tyr Arg Thr Trp Ala Tyr His Gly Ser Tyr Glu
2785 2790 2795
gct cct tcg aca ggc tct gca tcc tcc atg gtg aac ggg gta gta 8537
Ala Pro Ser Thr Gly Ser Ala Ser Ser Met Val Asn Gly Val Val
2800 2805 2810
aaa ctg cta aca aaa cct tgg gat gtg gtt cca atg gtg acc cag 8582
Lys Leu Leu Thr Lys Pro Trp Asp Val Val Pro Met Val Thr Gln
2815 2820 2825
tta gcc atg aca gac aca acc cct ttt ggg caa caa aga gtg ttc 8627
Leu Ala Met Thr Asp Thr Thr Pro Phe Gly Gln Gln Arg Val Phe
2830 2835 2840
aaa gag aag gtg gat acc aga aca cca caa cca aaa ccc ggt aca 8672
Lys Glu Lys Val Asp Thr Arg Thr Pro Gln Pro Lys Pro Gly Thr
2845 2850 2855
cga atg gtt atg acc acg aca gcc aat tgg ctg tgg gcc ctc ctt 8717
Arg Met Val Met Thr Thr Thr Ala Asn Trp Leu Trp Ala Leu Leu
2860 2865 2870
ggg aag aag aaa aat ccc aga ctg tgc aca agg gaa gag ttc atc 8762
Gly Lys Lys Lys Asn Pro Arg Leu Cys Thr Arg Glu Glu Phe Ile
2875 2880 2885
tca aaa gtt aga tca aac gca gcc ata ggc gca gtc ttt cag gaa 8807
Ser Lys Val Arg Ser Asn Ala Ala Ile Gly Ala Val Phe Gln Glu
2890 2895 2900
gaa cag gga tgg aca tca gcc agt gaa gct gtg aat gac agc cgg 8852
Glu Gln Gly Trp Thr Ser Ala Ser Glu Ala Val Asn Asp Ser Arg
2905 2910 2915
ttt tgg gaa ctg gtt gac aaa gaa agg gcc cta cac cag gaa ggg 8897
Phe Trp Glu Leu Val Asp Lys Glu Arg Ala Leu His Gln Glu Gly
2920 2925 2930
aaa tgt gaa tcg tgt gtc tac aac atg atg gga aaa cgt gag aaa 8942
Lys Cys Glu Ser Cys Val Tyr Asn Met Met Gly Lys Arg Glu Lys
2935 2940 2945
aag tta gga gag ttt ggc aga gcc aag gga agc cga gca atc tgg 8987
Lys Leu Gly Glu Phe Gly Arg Ala Lys Gly Ser Arg Ala Ile Trp
2950 2955 2960
tac atg tgg ctg gga gcg cgg ttt ctg gaa ttt gaa gcc ctg ggt 9032
Tyr Met Trp Leu Gly Ala Arg Phe Leu Glu Phe Glu Ala Leu Gly
2965 2970 2975
ttt ttg aat gaa gat cac tgg ttt ggc aga gaa aat tca tgg agt 9077
Phe Leu Asn Glu Asp His Trp Phe Gly Arg Glu Asn Ser Trp Ser
2980 2985 2990
gga gtg gaa ggg gaa ggt ctg cac aga ttg gga tat atc ctg gag 9122
Gly Val Glu Gly Glu Gly Leu His Arg Leu Gly Tyr Ile Leu Glu
2995 3000 3005
gag ata gac aag aag gat gga gac cta atg tat gct gat gac aca 9167
Glu Ile Asp Lys Lys Asp Gly Asp Leu Met Tyr Ala Asp Asp Thr
3010 3015 3020
gca ggc tgg gac aca aga atc act gag gat gac ctt caa aat gaa 9212
Ala Gly Trp Asp Thr Arg Ile Thr Glu Asp Asp Leu Gln Asn Glu
3025 3030 3035
gaa ctg atc acg gaa cag atg gcc ccc cac cac aag atc cta gcc 9257
Glu Leu Ile Thr Glu Gln Met Ala Pro His His Lys Ile Leu Ala
3040 3045 3050
aaa gcc att ttc aaa cta acc tat caa aac aaa gtg gtg aaa gtc 9302
Lys Ala Ile Phe Lys Leu Thr Tyr Gln Asn Lys Val Val Lys Val
3055 3060 3065
ctc aga ccc aca ccg aga gga gcg gtg atg gat atc ata tcc agg 9347
Leu Arg Pro Thr Pro Arg Gly Ala Val Met Asp Ile Ile Ser Arg
3070 3075 3080
aaa gac caa aga ggt agt gga caa gtt gga aca tat ggt ttg aac 9392
Lys Asp Gln Arg Gly Ser Gly Gln Val Gly Thr Tyr Gly Leu Asn
3085 3090 3095
aca ttc acc aac atg gaa gtt caa ctc atc cgc caa atg gaa gct 9437
Thr Phe Thr Asn Met Glu Val Gln Leu Ile Arg Gln Met Glu Ala
3100 3105 3110
gaa gga gtc atc aca caa gat gac atg cag aac cca aaa ggg ttg 9482
Glu Gly Val Ile Thr Gln Asp Asp Met Gln Asn Pro Lys Gly Leu
3115 3120 3125
aaa gaa aga gtt gag aaa tgg ctg aaa gag tgt ggt gtc gac agg 9527
Lys Glu Arg Val Glu Lys Trp Leu Lys Glu Cys Gly Val Asp Arg
3130 3135 3140
tta aag agg atg gca atc agt gga gac gat tgc gtg gtg aag ccc 9572
Leu Lys Arg Met Ala Ile Ser Gly Asp Asp Cys Val Val Lys Pro
3145 3150 3155
ctg gat gag agg ttt ggc act tcc ctc ctc ttc ttg aac gac atg 9617
Leu Asp Glu Arg Phe Gly Thr Ser Leu Leu Phe Leu Asn Asp Met
3160 3165 3170
gga aag gtg agg aaa gac att ccg cag tgg gaa cca tct aag gga 9662
Gly Lys Val Arg Lys Asp Ile Pro Gln Trp Glu Pro Ser Lys Gly
3175 3180 3185
tgg aaa aac tgg caa gag gtt cct ttt tgc tcc cac cac ttt cac 9707
Trp Lys Asn Trp Gln Glu Val Pro Phe Cys Ser His His Phe His
3190 3195 3200
aag atc ttc atg aag gat ggc cgc tca cta gtt gtt cca tgt aga 9752
Lys Ile Phe Met Lys Asp Gly Arg Ser Leu Val Val Pro Cys Arg
3205 3210 3215
aac cag gat gaa ctg ata ggg aga gcc aga atc tcg cag ggg gct 9797
Asn Gln Asp Glu Leu Ile Gly Arg Ala Arg Ile Ser Gln Gly Ala
3220 3225 3230
gga tgg agc tta aga gaa aca gcc tgc ctg ggc aaa gct tac gcc 9842
Gly Trp Ser Leu Arg Glu Thr Ala Cys Leu Gly Lys Ala Tyr Ala
3235 3240 3245
cag atg tgg tcg ctc atg tac ttc cac aga agg gat ctg cgt tta 9887
Gln Met Trp Ser Leu Met Tyr Phe His Arg Arg Asp Leu Arg Leu
3250 3255 3260
gcc tcc atg gcc ata tgc tca gca gtt cca acg gaa tgg ttt cca 9932
Ala Ser Met Ala Ile Cys Ser Ala Val Pro Thr Glu Trp Phe Pro
3265 3270 3275
aca agc aga aca aca tgg tca atc cac gct cat cat cag tgg atg 9977
Thr Ser Arg Thr Thr Trp Ser Ile His Ala His His Gln Trp Met
3280 3285 3290
acc act gaa gat atg ctc aaa gtg tgg aac aga gtg tgg ata gaa 10022
Thr Thr Glu Asp Met Leu Lys Val Trp Asn Arg Val Trp Ile Glu
3295 3300 3305
gac aac cct aat atg act gac aag act cca gtc cat tcg tgg gaa 10067
Asp Asn Pro Asn Met Thr Asp Lys Thr Pro Val His Ser Trp Glu
3310 3315 3320
gat ata cct tac cta ggg aaa aga gag gat ttg tgg tgt gga tcc 10112
Asp Ile Pro Tyr Leu Gly Lys Arg Glu Asp Leu Trp Cys Gly Ser
3325 3330 3335
ctg att gga ctt tct tcc aga gcc acc tgg gcg aag aac att cac 10157
Leu Ile Gly Leu Ser Ser Arg Ala Thr Trp Ala Lys Asn Ile His
3340 3345 3350
acg gcc ata acc cag gtc aga aac ctg atc gga aaa gag gaa tac 10202
Thr Ala Ile Thr Gln Val Arg Asn Leu Ile Gly Lys Glu Glu Tyr
3355 3360 3365
gtg gat tac atg cca gta atg aaa aga tac agc gct cct tca gag 10247
Val Asp Tyr Met Pro Val Met Lys Arg Tyr Ser Ala Pro Ser Glu
3370 3375 3380
agt gaa gga gtt ctg taa ttaccaacaa caaacaccaa aggctattga 10295
Ser Glu Gly Val Leu
3385
agtcaggcca cttgtgccac ggcttgagca aaccgtgctg cctgtagctc cgccaataat10355
gggaggcgtg aaatccctag ggaggccatg cgccacggaa gctgtacgcg tggcatattg10415
gactagcggt tagaggagac ccctcccatc actgacaaaa cgcagcaaaa gggggcccga10475
agccaggagg aagctgtact cctggtggaa ggactagagg ttagaggaga cccccccaac10535
acaaaaacag catattgacg ctgggaaaga ccagagatcc tgctgtctct gcaacatcaa10595
tccaggcaca gagcgaagca agatggattg gtgttgttga tccaacaggt tct 10648
<210> 10
<211> 3387
<212> PRT
<213> 4型登革病毒
<400> 10
Met Asn Gln Arg Lys Lys Val Val Arg Pro Pro Phe Asn Met Leu Lys
1 5 10 15
Arg Glu Arg Asn Arg Val Ser Thr Pro Gln Gly Leu Val Lys Arg Phe
20 25 30
Ser Thr Gly Leu Phe Ser Gly Lys Gly Pro Leu Arg Met Val Leu Ala
35 40 45
Phe Ile Thr Phe Leu Arg Val Leu Ser Ile Pro Pro Thr Ala Gly Ile
50 55 60
Leu Lys Arg Trp Gly Gln Leu Lys Lys Asn Lys Ala Ile Arg Ile Leu
65 70 75 80
Ile Gly Phe Arg Lys Glu Ile Gly Arg Met Leu Asn Ile Leu Asn Gly
85 90 95
Arg Lys Arg Ser Thr Ile Thr Leu Leu Cys Leu Ile Pro Thr Val Met
100 105 110
Ala Phe His Leu Ser Thr Arg Asp Gly Glu Pro Leu Met Ile Val Ala
115 120 125
Lys His Glu Arg Gly Arg Pro Leu Leu Phe Lys Thr Thr Glu Gly Ile
130 135 140
Asn Lys Cys Thr Leu Ile Ala Met Asp Leu Gly Glu Met Cys Glu Asp
145 150 155 160
Thr Val Thr Tyr Lys Cys Pro Leu Leu Val Asn Thr Glu Pro Glu Asp
165 170 175
Ile Asp Cys Trp Cys Asn Leu Thr Ser Thr Trp Val Met Tyr Gly Thr
180 185 190
Cys Thr Gln Ser Gly Glu Arg Arg Arg Glu Lys Arg Ser Val Ala Leu
195 200 205
Thr Pro His Ser Gly Met Gly Leu Glu Thr Arg Ala Glu Thr Trp Met
210 215 220
Ser Ser Glu Gly Ala Trp Lys His Ala Gln Arg Val Glu Ser Trp Ile
225 230 235 240
Leu Arg Asn Pro Gly Phe Ala Leu Leu Ala Gly Phe Met Ala Tyr Met
245 250 255
Ile Gly Gln Thr Gly Ile Gln Arg Thr Val Phe Phe Val Leu Met Met
260 265 270
Leu Val Ala Pro Ser Tyr Gly Met Arg Cys Val Gly Val Gly Asn Arg
275 280 285
Asp Phe Val Glu Gly Val Ser Gly Gly Ala Trp Val Asp Leu Val Leu
290 295 300
Glu His Gly Gly Cys Val Thr Thr Met Ala Gln Gly Lys Pro Thr Leu
305 310 315 320
Asp Phe Glu Leu Thr Lys Thr Thr Ala Lys Glu Val Ala Leu Leu Arg
325 330 335
Thr Tyr Cys Ile Glu Ala Ser Ile Ser Asn Ile Thr Thr Ala Thr Arg
340 345 350
Cys Pro Thr Gln Gly Glu Pro Tyr Leu Lys Glu Glu Gln Asp Gln Gln
355 360 365
Tyr Ile Cys Arg Arg Asp Val Val Asp Arg Gly Trp Gly Asn Gly Cys
370 375 380
Gly Leu Phe Gly Lys Gly Gly Val Val Thr Cys Ala Lys Phe Ser Cys
385 390 395 400
Ser Gly Lys Ile Thr Gly Asn Leu Val Gln Ile Glu Asn Leu Glu Tyr
405 410 415
Thr Val Val Val Thr Val His Asn Gly Asp Thr His Ala Val Gly Asn
420 425 430
Asp Thr Ser Asn His Gly Val Thr Ala Thr Ile Thr Pro Arg Ser Pro
435 440 445
Ser Val Glu Val Lys Leu Pro Asp Tyr Gly Glu Leu Thr Leu Asp Cys
450 455 460
Glu Pro Arg Ser Gly Ile Asp Phe Asn Glu Met Ile Leu Met Lys Met
465 470 475 480
Lys Lys Lys Thr Trp Leu Val His Lys Gln Trp Phe Leu Asp Leu Pro
485 490 495
Leu Pro Trp Thr Ala Gly Ala Asp Thr Ser Glu Val His Trp Asn Tyr
500 505 510
Lys Glu Arg Met Val Thr Phe Lys Val Pro His Ala Lys Arg Gln Asp
515 520 525
Val Thr Val Leu Gly Ser Gln Glu Gly Ala Met His Ser Ala Leu Ala
530 535 540
Gly Ala Thr Glu Val Asp Ser Gly Asp Gly Asn His Met Phe Ala Gly
545 550 555 560
His Leu Lys Cys Lys Val Arg Met Glu Lys Leu Arg Ile Lys Gly Met
565 570 575
Ser Tyr Thr Met Cys Ser Gly Lys Phe Ser Ile Asp Lys Glu Met Ala
580 585 590
Glu Thr Gln His Gly Thr Thr Val Val Lys Val Lys Tyr Glu Gly Ala
595 600 605
Gly Ala Pro Cys Lys Val Pro Ile Glu Ile Arg Asp Val Asn Lys Glu
610 615 620
Lys Val Val Gly Arg Ile Ile Ser Ser Thr Pro Leu Ala Glu Asn Thr
625 630 635 640
Asn Ser Ala Thr Asn Ile Glu Leu Glu Pro Pro Phe Gly Asp Ser Tyr
645 650 655
Ile Val Ile Gly Val Gly Asn Ser Ala Leu Thr Leu His Trp Phe Arg
660 665 670
Lys Gly Ser Ser Ile Gly Lys Met Phe Glu Ser Thr Tyr Arg Gly Ala
675 680 685
Lys Arg Met Ala Ile Leu Gly Glu Thr Ala Trp Asp Phe Gly Ser Val
690 695 700
Gly Gly Leu Phe Thr Ser Leu Gly Lys Ala Val His Gln Val Phe Gly
705 710 715 720
Ser Val Tyr Thr Thr Met Phe Gly Gly Val Ser Trp Met Ile Arg Ile
725 730 735
Leu Ile Gly Phe Leu Val Leu Trp Ile Gly Thr Asn Ser Arg Asn Thr
740 745 750
Ser Met Ala Met Thr Cys Ile Ala Val Gly Gly Ile Thr Leu Phe Leu
755 760 765
Gly Phe Thr Val Gln Ala Asp Met Gly Cys Val Val Ser Trp Ser Gly
770 775 780
Lys Glu Leu Lys Cys Gly Ser Gly Ile Phe Val Val Asp Asn Val His
785 790 795 800
Thr Trp Thr Glu Gln Tyr Lys Phe Gln Pro Glu Ser Pro Ala Arg Leu
805 810 815
Ala Ser Ala Ile Leu Asn Ala His Lys Asp Gly Val Cys Gly Ile Arg
820 825 830
Ser Thr Thr Arg Leu Glu Asn Val Met Trp Lys Gln Ile Thr Asn Glu
835 840 845
Leu Asn Tyr Val Leu Trp Glu Gly Gly His Asp Leu Thr Val Val Ala
850 855 860
Gly Asp Val Lys Gly Val Leu Thr Lys Gly Lys Arg Ala Leu Thr Pro
865 870 875 880
Pro Val Asn Asp Leu Lys Tyr Ser Trp Lys Thr Trp Gly Lys Ala Lys
885 890 895
Ile Phe Thr Pro Glu Ala Arg Asn Ser Thr Phe Leu Ile Asp Gly Pro
900 905 910
Asp Thr Ser Glu Cys Pro Asn Glu Arg Arg Ala Trp Asn Phe Leu Glu
915 920 925
Val Glu Asp Tyr Gly Phe Gly Met Phe Thr Thr Asn Ile Trp Met Lys
930 935 940
Phe Arg Glu Gly Ser Ser Glu Val Cys Asp His Arg Leu Met Ser Ala
945 950 955 960
Ala Ile Lys Asp Gln Lys Ala Val His Ala Asp Met Gly Tyr Trp Ile
965 970 975
Glu Ser Ser Lys Asn Gln Thr Trp Gln Ile Glu Lys Ala Ser Leu Ile
980 985 990
Glu Val Lys Thr Cys Leu Trp Pro Lys Thr His Thr Leu Trp Ser Asn
995 1000 1005
Gly Val Leu Glu Ser Gln Met Leu Ile Pro Lys Ser Tyr Ala Gly
1010 1015 1020
Pro Phe Ser Gln His Asn Tyr Arg Gln Gly Tyr Ala Thr Gln Thr
1025 1030 1035
Val Gly Pro Trp His Leu Gly Lys Leu Glu Ile Asp Phe Gly Glu
1040 1045 1050
Cys Pro Gly Thr Thr Val Ala Ile Gln Glu Asp Cys Asp His Arg
1055 1060 1065
Gly Pro Ser Leu Arg Thr Thr Thr Ala Ser Gly Lys Leu Val Thr
1070 1075 1080
Gln Trp Cys Cys Arg Ser Cys Thr Met Pro Pro Leu Arg Phe Leu
1085 1090 1095
Gly Glu Asp Gly Cys Trp Tyr Gly Met Glu Ile Arg Pro Leu Ser
1100 1105 1110
Glu Lys Glu Glu Asn Met Val Lys Ser Gln Val Thr Ala Gly Gln
1115 1120 1125
Gly Thr Ser Glu Thr Phe Ser Met Gly Leu Leu Cys Leu Thr Leu
1130 1135 1140
Phe Val Glu Glu Cys Leu Arg Arg Arg Val Thr Arg Lys His Met
1145 1150 1155
Ile Leu Val Val Val Ile Thr Leu Cys Ala Ile Ile Leu Gly Gly
1160 1165 1170
Leu Thr Trp Met Asp Leu Leu Arg Ala Leu Ile Met Leu Gly Asp
1175 1180 1185
Thr Met Ser Gly Arg Ile Gly Gly Gln Ile His Leu Ala Ile Met
1190 1195 1200
Ala Val Phe Lys Met Ser Pro Gly Tyr Val Leu Gly Val Phe Leu
1205 1210 1215
Arg Lys Leu Thr Ser Arg Glu Thr Ala Leu Met Val Ile Gly Met
1220 1225 1230
Ala Met Thr Thr Val Leu Ser Ile Pro His Asp Leu Met Glu Leu
1235 1240 1245
Ile Asp Gly Ile Ser Leu Gly Leu Ile Leu Leu Lys Ile Val Thr
1250 1255 1260
His Phe Asp Asn Thr Gln Val Gly Thr Leu Ala Leu Ser Leu Thr
1265 1270 1275
Phe Ile Arg Ser Thr Met Pro Leu Val Met Ala Trp Arg Thr Ile
1280 1285 1290
Met Ala Val Leu Phe Val Val Thr Leu Ile Pro Leu Cys Arg Thr
1295 1300 1305
Ser Cys Leu Gln Lys Gln Ser His Trp Val Glu Ile Thr Ala Leu
1310 1315 1320
Ile Leu Gly Ala Gln Ala Leu Pro Val Tyr Leu Met Thr Leu Met
1325 1330 1335
Lys Gly Ala Ser Arg Arg Ser Trp Pro Leu Asn Glu Gly Ile Met
1340 1345 1350
Ala Val Gly Leu Val Ser Leu Leu Gly Ser Ala Leu Leu Lys Asn
1355 1360 1365
Asp Val Pro Leu Ala Gly Pro Met Val Ala Gly Gly Leu Leu Leu
1370 1375 1380
Ala Ala Tyr Val Met Ser Gly Ser Ser Ala Asp Leu Ser Leu Glu
1385 1390 1395
Lys Ala Ala Asn Val Gln Trp Asp Glu Met Ala Asp Ile Thr Gly
1400 1405 1410
Ser Ser Pro Ile Ile Glu Val Lys Gln Asp Glu Asp Gly Ser Phe
1415 1420 1425
Ser Ile Arg Asp Val Glu Glu Thr Asn Met Ile Thr Leu Leu Val
1430 1435 1440
Lys Leu Ala Leu Ile Thr Val Ser Gly Leu Tyr Pro Leu Ala Ile
1445 1450 1455
Pro Val Thr Met Thr Leu Trp Tyr Met Trp Gln Val Lys Thr Gln
1460 1465 1470
Arg Ser Gly Ala Leu Trp Asp Val Pro Ser Pro Ala Ala Thr Gln
1475 1480 1485
Lys Ala Ala Leu Ser Glu Gly Val Tyr Arg Ile Met Gln Arg Gly
1490 1495 1500
Leu Phe Gly Lys Thr Gln Val Gly Val Gly Ile His Met Glu Gly
1505 1510 1515
Val Phe His Thr Met Trp His Val Thr Arg Gly Ser Val Ile Cys
1520 1525 1530
His Glu Thr Gly Arg Leu Glu Pro Ser Trp Ala Asp Val Arg Asn
1535 1540 1545
Asp Met Ile Ser Tyr Gly Gly Gly Trp Arg Leu Gly Asp Lys Trp
1550 1555 1560
Asp Lys Glu Glu Asp Val Gln Val Leu Ala Ile Glu Pro Gly Lys
1565 1570 1575
Asn Pro Lys His Val Gln Thr Lys Pro Gly Leu Phe Lys Thr Leu
1580 1585 1590
Thr Gly Glu Ile Gly Ala Val Thr Leu Asp Phe Lys Pro Gly Thr
1595 1600 1605
Ser Gly Ser Pro Ile Ile Asn Arg Lys Gly Lys Val Ile Gly Leu
1610 1615 1620
Tyr Gly Asn Gly Val Val Thr Lys Ser Gly Asp Tyr Val Ser Ala
1625 1630 1635
Ile Thr Gln Ala Glu Arg Ile Gly Glu Pro Asp Tyr Glu Val Asp
1640 1645 1650
Glu Asp Ile Phe Arg Lys Lys Arg Leu Thr Ile Met Asp Leu His
1655 1660 1665
Pro Gly Ala Gly Lys Thr Lys Arg Ile Leu Pro Ser Ile Val Arg
1670 1675 1680
Glu Ala Leu Lys Arg Arg Leu Arg Thr Leu Ile Leu Ala Pro Thr
1685 1690 1695
Arg Val Val Ala Ala Glu Met Glu Glu Ala Leu Arg Gly Leu Pro
1700 1705 1710
Ile Arg Tyr Gln Thr Pro Ala Val Lys Ser Glu His Thr Gly Arg
1715 1720 1725
Glu Ile Val Asp Leu Met Cys His Ala Thr Phe Thr Thr Arg Leu
1730 1735 1740
Leu Ser Ser Thr Arg Val Pro Asn Tyr Asn Leu Ile Val Met Asp
1745 1750 1755
Glu Ala His Phe Thr Asp Pro Ser Ser Val Ala Ala Arg Gly Tyr
1760 1765 1770
Ile Ser Thr Arg Val Glu Met Gly Glu Ala Ala Ala Ile Phe Met
1775 1780 1785
Thr Ala Thr Pro Pro Gly Ala Thr Asp Pro Phe Pro Gln Ser Asn
1790 1795 1800
Ser Pro Ile Glu Asp Ile Glu Arg Glu Ile Pro Glu Arg Ser Trp
1805 1810 1815
Asn Thr Gly Phe Asp Trp Ile Thr Asp Tyr Gln Gly Lys Thr Val
1820 1825 1830
Trp Phe Val Pro Ser Ile Lys Ala Gly Asn Asp Ile Ala Asn Cys
1835 1840 1845
Leu Arg Lys Ser Gly Lys Lys Val Ile Gln Leu Ser Arg Lys Thr
1850 1855 1860
Phe Asp Thr Glu Tyr Pro Lys Thr Lys Leu Thr Asp Trp Asp Phe
1865 1870 1875
Val Val Thr Thr Asp Ile Ser Glu Met Gly Ala Asn Phe Arg Ala
1880 1885 1890
Gly Arg Val Ile Asp Pro Arg Arg Cys Leu Lys Pro Val Ile Leu
1895 1900 1905
Thr Asp Gly Pro Glu Arg Val Ile Leu Ala Gly Pro Ile Pro Val
1910 1915 1920
Thr Pro Ala Ser Ala Ala Gln Arg Arg Gly Arg Ile Gly Arg Asn
1925 1930 1935
Pro Ala Gln Glu Asp Asp Gln Tyr Val Phe Ser Gly Asp Pro Leu
1940 1945 1950
Lys Asn Asp Glu Asp His Ala His Trp Thr Glu Ala Lys Met Leu
1955 1960 1965
Leu Asp Asn Ile Tyr Thr Pro Glu Gly Ile Ile Pro Thr Leu Phe
1970 1975 1980
Gly Pro Glu Arg Glu Lys Thr Gln Ala Ile Asp Gly Glu Phe Arg
1985 1990 1995
Leu Arg Gly Glu Gln Arg Lys Thr Phe Val Glu Leu Met Arg Arg
2000 2005 2010
Gly Asp Leu Pro Val Trp Leu Ser Tyr Lys Val Ala Ser Ala Gly
2015 2020 2025
Ile Ser Tyr Lys Asp Arg Glu Trp Cys Phe Thr Gly Glu Arg Asn
2030 2035 2040
Asn Gln Ile Leu Glu Glu Asn Met Glu Val Glu Ile Trp Thr Arg
2045 2050 2055
Glu Gly Glu Lys Lys Lys Leu Arg Pro Arg Trp Leu Asp Ala Arg
2060 2065 2070
Val Tyr Ala Asp Pro Met Ala Leu Lys Asp Phe Lys Glu Phe Ala
2075 2080 2085
Ser Gly Arg Lys Ser Ile Thr Leu Asp Ile Leu Thr Glu Ile Ala
2090 2095 2100
Ser Leu Pro Thr Tyr Leu Ser Ser Arg Ala Lys Leu Ala Leu Asp
2105 2110 2115
Asn Ile Val Met Leu His Thr Thr Glu Arg Gly Gly Arg Ala Tyr
2120 2125 2130
Gln His Ala Leu Asn Glu Leu Pro Glu Ser Leu Glu Thr Leu Met
2135 2140 2145
Leu Val Ala Leu Leu Gly Ala Met Thr Ala Gly Ile Phe Leu Phe
2150 2155 2160
Phe Met Gln Gly Lys Gly Ile Gly Lys Leu Ser Met Gly Leu Ile
2165 2170 2175
Thr Ile Ala Val Ala Ser Gly Leu Leu Trp Val Ala Glu Ile Gln
2180 2185 2190
Pro Gln Trp Ile Ala Ala Ser Ile Ile Leu Glu Phe Phe Leu Met
2195 2200 2205
Val Leu Leu Ile Pro Glu Pro Glu Lys Gln Arg Thr Pro Gln Asp
2210 2215 2220
Asn Gln Leu Ile Tyr Val Ile Leu Thr Ile Leu Thr Ile Ile Gly
2225 2230 2235
Leu Ile Ala Ala Asn Glu Met Gly Leu Ile Glu Lys Thr Lys Thr
2240 2245 2250
Asp Phe Gly Phe Tyr Gln Val Lys Thr Glu Thr Thr Ile Leu Asp
2255 2260 2265
Val Asp Leu Arg Pro Ala Ser Ala Trp Thr Leu Tyr Ala Val Ala
2270 2275 2280
Thr Thr Ile Leu Thr Pro Met Leu Arg His Thr Ile Glu Asn Thr
2285 2290 2295
Ser Ala Asn Leu Ser Leu Ala Ala Ile Ala Asn Gln Ala Ala Val
2300 2305 2310
Leu Met Gly Leu Gly Lys Gly Trp Pro Leu His Arg Met Asp Leu
2315 2320 2325
Gly Val Pro Leu Leu Ala Met Gly Cys Tyr Ser Gln Val Asn Pro
2330 2335 2340
Thr Thr Leu Thr Ala Ser Leu Val Met Leu Leu Val His Tyr Ala
2345 2350 2355
Ile Ile Gly Pro Gly Leu Gln Ala Lys Ala Thr Arg Glu Ala Gln
2360 2365 2370
Lys Arg Thr Ala Ala Gly Ile Met Lys Asn Pro Thr Val Asp Gly
2375 2380 2385
Ile Thr Val Ile Asp Leu Glu Pro Ile Ser Tyr Asp Pro Lys Phe
2390 2395 2400
Glu Lys Gln Leu Gly Gln Val Met Leu Leu Val Leu Cys Ala Gly
2405 2410 2415
Gln Leu Leu Leu Met Arg Thr Thr Trp Ala Phe Cys Glu Val Leu
2420 2425 2430
Thr Leu Ala Thr Gly Pro Ile Leu Thr Leu Trp Glu Gly Asn Pro
2435 2440 2445
Gly Arg Phe Trp Asn Thr Thr Ile Ala Val Ser Thr Ala Asn Ile
2450 2455 2460
Phe Arg Gly Ser Tyr Leu Ala Gly Ala Gly Leu Ala Phe Ser Leu
2465 2470 2475
Ile Lys Asn Ala Gln Thr Pro Arg Arg Gly Thr Gly Thr Thr Gly
2480 2485 2490
Glu Thr Leu Gly Glu Lys Trp Lys Arg Gln Leu Asn Ser Leu Asp
2495 2500 2505
Arg Lys Glu Phe Glu Glu Tyr Lys Arg Ser Gly Ile Leu Glu Val
2510 2515 2520
Asp Arg Thr Glu Ala Lys Ser Ala Leu Lys Asp Gly Ser Lys Ile
2525 2530 2535
Lys His Ala Val Ser Arg Gly Ser Ser Lys Ile Arg Trp Ile Val
2540 2545 2550
Glu Arg Gly Met Val Lys Pro Lys Gly Lys Val Val Asp Leu Gly
2555 2560 2565
Cys Gly Arg Gly Gly Trp Ser Tyr Tyr Met Ala Thr Leu Lys Asn
2570 2575 2580
Val Thr Glu Val Lys Gly Tyr Thr Lys Gly Gly Pro Gly His Glu
2585 2590 2595
Glu Pro Ile Pro Met Ala Thr Tyr Gly Trp Asn Leu Val Lys Leu
2600 2605 2610
His Ser Gly Val Asp Val Phe Tyr Lys Pro Thr Glu Gln Val Asp
2615 2620 2625
Thr Leu Leu Cys Asp Ile Gly Glu Ser Ser Ser Asn Pro Thr Ile
2630 2635 2640
Glu Glu Gly Arg Thr Leu Arg Val Leu Lys Met Val Glu Pro Trp
2645 2650 2655
Leu Ser Ser Lys Pro Glu Phe Cys Ile Lys Val Leu Asn Pro Tyr
2660 2665 2670
Met Pro Thr Val Ile Glu Glu Leu Glu Lys Leu Gln Arg Lys His
2675 2680 2685
Gly Gly Asn Leu Val Arg Cys Pro Leu Ser Arg Asn Ser Thr His
2690 2695 2700
Glu Met Tyr Trp Val Ser Gly Ala Ser Gly Asn Ile Val Ser Ser
2705 2710 2715
Val Asn Thr Thr Ser Lys Met Leu Leu Asn Arg Phe Thr Thr Arg
2720 2725 2730
His Arg Lys Pro Thr Tyr Glu Lys Asp Val Asp Leu Gly Ala Gly
2735 2740 2745
Thr Arg Ser Val Ser Thr Glu Thr Glu Lys Pro Asp Met Thr Ile
2750 2755 2760
Ile Gly Arg Arg Leu Gln Arg Leu Gln Glu Glu His Lys Glu Thr
2765 2770 2775
Trp His Tyr Asp Gln Glu Asn Pro Tyr Arg Thr Trp Ala Tyr His
2780 2785 2790
Gly Ser Tyr Glu Ala Pro Ser Thr Gly Ser Ala Ser Ser Met Val
2795 2800 2805
Asn Gly Val Val Lys Leu Leu Thr Lys Pro Trp Asp Val Val Pro
2810 2815 2820
Met Val Thr Gln Leu Ala Met Thr Asp Thr Thr Pro Phe Gly Gln
2825 2830 2835
Gln Arg Val Phe Lys Glu Lys Val Asp Thr Arg Thr Pro Gln Pro
2840 2845 2850
Lys Pro Gly Thr Arg Met Val Met Thr Thr Thr Ala Asn Trp Leu
2855 2860 2865
Trp Ala Leu Leu Gly Lys Lys Lys Asn Pro Arg Leu Cys Thr Arg
2870 2875 2880
Glu Glu Phe Ile Ser Lys Val Arg Ser Asn Ala Ala Ile Gly Ala
2885 2890 2895
Val Phe Gln Glu Glu Gln Gly Trp Thr Ser Ala Ser Glu Ala Val
2900 2905 2910
Asn Asp Ser Arg Phe Trp Glu Leu Val Asp Lys Glu Arg Ala Leu
2915 2920 2925
His Gln Glu Gly Lys Cys Glu Ser Cys Val Tyr Asn Met Met Gly
2930 2935 2940
Lys Arg Glu Lys Lys Leu Gly Glu Phe Gly Arg Ala Lys Gly Ser
2945 2950 2955
Arg Ala Ile Trp Tyr Met Trp Leu Gly Ala Arg Phe Leu Glu Phe
2960 2965 2970
Glu Ala Leu Gly Phe Leu Asn Glu Asp His Trp Phe Gly Arg Glu
2975 2980 2985
Asn Ser Trp Ser Gly Val Glu Gly Glu Gly Leu His Arg Leu Gly
2990 2995 3000
Tyr Ile Leu Glu Glu Ile Asp Lys Lys Asp Gly Asp Leu Met Tyr
3005 3010 3015
Ala Asp Asp Thr Ala Gly Trp Asp Thr Arg Ile Thr Glu Asp Asp
3020 3025 3030
Leu Gln Asn Glu Glu Leu Ile Thr Glu Gln Met Ala Pro His His
3035 3040 3045
Lys Ile Leu Ala Lys Ala Ile Phe Lys Leu Thr Tyr Gln Asn Lys
3050 3055 3060
Val Val Lys Val Leu Arg Pro Thr Pro Arg Gly Ala Val Met Asp
3065 3070 3075
Ile Ile Ser Arg Lys Asp Gln Arg Gly Ser Gly Gln Val Gly Thr
3080 3085 3090
Tyr Gly Leu Asn Thr Phe Thr Asn Met Glu Val Gln Leu Ile Arg
3095 3100 3105
Gln Met Glu Ala Glu Gly Val Ile Thr Gln Asp Asp Met Gln Asn
3110 3115 3120
Pro Lys Gly Leu Lys Glu Arg Val Glu Lys Trp Leu Lys Glu Cys
3125 3130 3135
Gly Val Asp Arg Leu Lys Arg Met Ala Ile Ser Gly Asp Asp Cys
3140 3145 3150
Val Val Lys Pro Leu Asp Glu Arg Phe Gly Thr Ser Leu Leu Phe
3155 3160 3165
Leu Asn Asp Met Gly Lys Val Arg Lys Asp Ile Pro Gln Trp Glu
3170 3175 3180
Pro Ser Lys Gly Trp Lys Asn Trp Gln Glu Val Pro Phe Cys Ser
3185 3190 3195
His His Phe His Lys Ile Phe Met Lys Asp Gly Arg Ser Leu Val
3200 3205 3210
Val Pro Cys Arg Asn Gln Asp Glu Leu Ile Gly Arg Ala Arg Ile
3215 3220 3225
Ser Gln Gly Ala Gly Trp Ser Leu Arg Glu Thr Ala Cys Leu Gly
3230 3235 3240
Lys Ala Tyr Ala Gln Met Trp Ser Leu Met Tyr Phe His Arg Arg
3245 3250 3255
Asp Leu Arg Leu Ala Ser Met Ala Ile Cys Ser Ala Val Pro Thr
3260 3265 3270
Glu Trp Phe Pro Thr Ser Arg Thr Thr Trp Ser Ile His Ala His
3275 3280 3285
His Gln Trp Met Thr Thr Glu Asp Met Leu Lys Val Trp Asn Arg
3290 3295 3300
Val Trp Ile Glu Asp Asn Pro Asn Met Thr Asp Lys Thr Pro Val
3305 3310 3315
His Ser Trp Glu Asp Ile Pro Tyr Leu Gly Lys Arg Glu Asp Leu
3320 3325 3330
Trp Cys Gly Ser Leu Ile Gly Leu Ser Ser Arg Ala Thr Trp Ala
3335 3340 3345
Lys Asn Ile His Thr Ala Ile Thr Gln Val Arg Asn Leu Ile Gly
3350 3355 3360
Lys Glu Glu Tyr Val Asp Tyr Met Pro Val Met Lys Arg Tyr Ser
3365 3370 3375
Ala Pro Ser Glu Ser Glu Gly Val Leu
3380 3385
<210> 11
<211> 10996
<212> DNA
<213> 人工序列
<220>
<223> 西尼罗/登革 1 病毒嵌合体
<220>
<221> CDS
<222> (97)..(10365)
<400> 11
agtagttcgc ctgtgtgagc tgacaaactt agtagtgttt gtgaggatta acaacaatta 60
acacagtgcg agctgtttct tagcacgaag atctcg atg tct aag aaa cca gga 114
Met Ser Lys Lys Pro Gly
1 5
ggg ccc ggc aag agc cgg gct gtc aat atg cta aaa cgc gga atg ccc 162
Gly Pro Gly Lys Ser Arg Ala Val Asn Met Leu Lys Arg Gly Met Pro
10 15 20
cgc gtg ttg tcc ttg att gga ctg aag agg gct atg ttg agc ctg atc 210
Arg Val Leu Ser Leu Ile Gly Leu Lys Arg Ala Met Leu Ser Leu Ile
25 30 35
gac ggc aag ggg cca ata cga ttt gtg ttg gct ctc ttg gcg ttc ttc 258
Asp Gly Lys Gly Pro Ile Arg Phe Val Leu Ala Leu Leu Ala Phe Phe
40 45 50
agg ttc aca gca att gct ccg acc cga gca gtg ctg gat cga tgg aga 306
Arg Phe Thr Ala Ile Ala Pro Thr Arg Ala Val Leu Asp Arg Trp Arg
55 60 65 70
ggt gtg aac aaa caa aca gcg atg aaa cac ctt ctg agt ttt aag aag 354
Gly Val Asn Lys Gln Thr Ala Met Lys His Leu Leu Ser Phe Lys Lys
75 80 85
gaa cta ggg acc ttg acc agt gct atc aat cgg cgg agt tcg aaa caa 402
Glu Leu Gly Thr Leu Thr Ser Ala Ile Asn Arg Arg Ser Ser Lys Gln
90 95 100
aag aaa aga tcc gtg acc atg ctc ctt atg ctg ctg ccc aca gcc ctg 450
Lys Lys Arg Ser Val Thr Met Leu Leu Met Leu Leu Pro Thr Ala Leu
105 110 115
gcg ttc cat ctg acg aca cga ggg gga gag ccg cat atg ata gtt agc 498
Ala Phe His Leu Thr Thr Arg Gly Gly Glu Pro His Met Ile Val Ser
120 125 130
aag cag gaa aga gga aag tca ctt ttg ttc aag acc tct gca ggt gtc 546
Lys Gln Glu Arg Gly Lys Ser Leu Leu Phe Lys Thr Ser Ala Gly Val
135 140 145 150
aac atg tgc acc ctc att gcg atg gat ttg gga gag ttg tgt gag gac 594
Asn Met Cys Thr Leu Ile Ala Met Asp Leu Gly Glu Leu Cys Glu Asp
155 160 165
acg atg acc tac aaa tgc ccc cgg atc act gag gcg gaa cca gat gac 642
Thr Met Thr Tyr Lys Cys Pro Arg Ile Thr Glu Ala Glu Pro Asp Asp
170 175 180
gtt gac tgt tgg tgc aat gcc acg gac aca tgg gtg acc tat gga acg 690
Val Asp Cys Trp Cys Asn Ala Thr Asp Thr Trp Val Thr Tyr Gly Thr
185 190 195
tgc tct caa act ggc gaa cac cga cga gac aaa cgt tcc gtc gca ttg 738
Cys Ser Gln Thr Gly Glu His Arg Arg Asp Lys Arg Ser Val Ala Leu
200 205 210
gcc cca cac gtg ggg ctt ggc cta gaa aca aga gcc gaa acg tgg atg 786
Ala Pro His Val Gly Leu Gly Leu Glu Thr Arg Ala Glu Thr Trp Met
215 220 225 230
tcc tct gaa ggt gct tgg aaa cag ata caa aaa gta gag act tgg gct 834
Ser Ser Glu Gly Ala Trp Lys Gln Ile Gln Lys Val Glu Thr Trp Ala
235 240 245
ctg aga cat cca gga ttc acg gtg ata gcc ctt ttt cta gca cat gcc 882
Leu Arg His Pro Gly Phe Thr Val Ile Ala Leu Phe Leu Ala His Ala
250 255 260
ata gga aca tcc atc acc cag aaa ggg atc att ttc att ttg ctg atg 930
Ile Gly Thr Ser Ile Thr Gln Lys Gly Ile Ile Phe Ile Leu Leu Met
265 270 275
ctg gta aca cca tct atg gcc atg cga tgc gtg gga ata ggc aac aga 978
Leu Val Thr Pro Ser Met Ala Met Arg Cys Val Gly Ile Gly Asn Arg
280 285 290
gac ttc gtg gaa gga ctg tca gga gca aca tgg gtg gat gtg gta ctg 1026
Asp Phe Val Glu Gly Leu Ser Gly Ala Thr Trp Val Asp Val Val Leu
295 300 305 310
gag cat gga agt tgc gtc acc acc atg gca aaa aac aaa cca aca ctg 1074
Glu His Gly Ser Cys Val Thr Thr Met Ala Lys Asn Lys Pro Thr Leu
315 320 325
gac att gaa ctc ttg aag acg gag gtc aca aac cct gca gtt ctg cgt 1122
Asp Ile Glu Leu Leu Lys Thr Glu Val Thr Asn Pro Ala Val Leu Arg
330 335 340
aaa ttg tgc att gaa gct aaa ata tca aac acc acc acc gat tcg aga 1170
Lys Leu Cys Ile Glu Ala Lys Ile Ser Asn Thr Thr Thr Asp Ser Arg
345 350 355
tgt cca aca caa gga gaa gcc aca ctg gtg gaa gaa caa gac gcg aac 1218
Cys Pro Thr Gln Gly Glu Ala Thr Leu Val Glu Glu Gln Asp Ala Asn
360 365 370
ttt gtg tgc cga cga acg ttc gtg gac aga ggc tgg ggc aat ggc tgt 1266
Phe Val Cys Arg Arg Thr Phe Val Asp Arg Gly Trp Gly Asn Gly Cys
375 380 385 390
ggg cta ttc gga aaa ggt agt cta ata acg tgt gcc aag ttt aag tgt 1314
Gly Leu Phe Gly Lys Gly Ser Leu Ile Thr Cys Ala Lys Phe Lys Cys
395 400 405
gtg aca aaa cta gaa gga aag ata gtt caa tat gaa aac cta aaa tat 1362
Val Thr Lys Leu Glu Gly Lys Ile Val Gln Tyr Glu Asn Leu Lys Tyr
410 415 420
tca gtg ata gtc acc gtc cac act gga gat cag cac cag gtg gga aat 1410
Ser Val Ile Val Thr Val His Thr Gly Asp Gln His Gln Val Gly Asn
425 430 435
gag act aca gaa cat gga aca act gca acc ata aca cct caa gct cct 1458
Glu Thr Thr Glu His Gly Thr Thr Ala Thr Ile Thr Pro Gln Ala Pro
440 445 450
acg tcg gaa ata cag ctg acc gac tac gga acc ctt aca tta gat tgt 1506
Thr Ser Glu Ile Gln Leu Thr Asp Tyr Gly Thr Leu Thr Leu Asp Cys
455 460 465 470
tca cct agg aca ggg cta gat ttt aac gag atg gtg ttg ctg aca atg 1554
Ser Pro Arg Thr Gly Leu Asp Phe Asn Glu Met Val Leu Leu Thr Met
475 480 485
aaa gaa aga tca tgg ctt gtc cac aaa caa tgg ttc cta gac tta cca 1602
Lys Glu Arg Ser Trp Leu Val His Lys Gln Trp Phe Leu Asp Leu Pro
490 495 500
ctg cct tgg acc tct ggg gct tca aca tcc caa gag act tgg aac aga 1650
Leu Pro Trp Thr Ser Gly Ala Ser Thr Ser Gln Glu Thr Trp Asn Arg
505 510 515
caa gat tta ctg gtc aca ttt aag aca gct cat gca aag aag cag gaa 1698
Gln Asp Leu Leu Val Thr Phe Lys Thr Ala His Ala Lys Lys Gln Glu
520 525 530
gta gtc gta cta gga tca caa gaa gga gca atg cac act gcg ctg act 1746
Val Val Val Leu Gly Ser Gln Glu Gly Ala Met His Thr Ala Leu Thr
535 540 545 550
gga gcg aca gaa atc caa acg tca gga acg aca aca att ttc gca gga 1794
Gly Ala Thr Glu Ile Gln Thr Ser Gly Thr Thr Thr Ile Phe Ala Gly
555 560 565
cac cta aaa tgc aga cta aaa atg gac aaa cta act tta aaa ggg atg 1842
His Leu Lys Cys Arg Leu Lys Met Asp Lys Leu Thr Leu Lys Gly Met
570 575 580
tca tat gtg atg tgc aca ggc tca ttc aag tta gag aaa gaa gtg gct 1890
Ser Tyr Val Met Cys Thr Gly Ser Phe Lys Leu Glu Lys Glu Val Ala
585 590 595
gag acc cag cat gga act gtt ctg gtg cag gtt aaa tat gaa gga aca 1938
Glu Thr Gln His Gly Thr Val Leu Val Gln Val Lys Tyr Glu Gly Thr
600 605 610
gac gca cca tgc aag att ccc ttt tcg acc caa gat gag aaa gga gca 1986
Asp Ala Pro Cys Lys Ile Pro Phe Ser Thr Gln Asp Glu Lys Gly Ala
615 620 625 630
acc cag aat ggg aga tta ata aca gcc aac ccc ata gtc act gac aaa 2034
Thr Gln Asn Gly Arg Leu Ile Thr Ala Asn Pro Ile Val Thr Asp Lys
635 640 645
gaa aaa cca gtc aat att gag gca gaa cca ccc ttt ggt gag agc tac 2082
Glu Lys Pro Val Asn Ile Glu Ala Glu Pro Pro Phe Gly Glu Ser Tyr
650 655 660
atc gtg gta gga gca ggt gaa aaa gct ttg aaa cta agc tgg ttc aag 2130
Ile Val Val Gly Ala Gly Glu Lys Ala Leu Lys Leu Ser Trp Phe Lys
665 670 675
aaa gga agc agc ata ggg aaa atg ttt gaa gca act gcc cga gga gca 2178
Lys Gly Ser Ser Ile Gly Lys Met Phe Glu Ala Thr Ala Arg Gly Ala
680 685 690
cga agg atg gcc att ctg gga gac acc gca tgg gac ttc ggt tct ata 2226
Arg Arg Met Ala Ile Leu Gly Asp Thr Ala Trp Asp Phe Gly Ser Ile
695 700 705 710
gga gga gtg ttc acg tct atg gga aaa ctg gta cac cag gtt ttt gga 2274
Gly Gly Val Phe Thr Ser Met Gly Lys Leu Val His Gln Val Phe Gly
715 720 725
act gca tat gga gtt ttg ttt agc gga gtt tct tgg acc atg aaa ata 2322
Thr Ala Tyr Gly Val Leu Phe Ser Gly Val Ser Trp Thr Met Lys Ile
730 735 740
gga ata ggg att ctg ctg aca tgg cta gga tta aat tca agg aac acg 2370
Gly Ile Gly Ile Leu Leu Thr Trp Leu Gly Leu Asn Ser Arg Asn Thr
745 750 755
tcc ctt tcg atg atg tgc atc gca gtt ggc atg gtc aca ctg tac cta 2418
Ser Leu Ser Met Met Cys Ile Ala Val Gly Met Val Thr Leu Tyr Leu
760 765 770
gga gtc atg gtt cag gca gat tcc gga tgt gcc ata gac atc agc cgg 2466
Gly Val Met Val Gln Ala Asp Ser Gly Cys Ala Ile Asp Ile Ser Arg
775 780 785 790
caa gag ctg aga tgt gga agt gga gtg ttc ata cac aat gat gtg gag 2514
Gln Glu Leu Arg Cys Gly Ser Gly Val Phe Ile His Asn Asp Val Glu
795 800 805
gct tgg atg gac cgg tac aag tat tac cct gaa acg cca caa ggc cta 2562
Ala Trp Met Asp Arg Tyr Lys Tyr Tyr Pro Glu Thr Pro Gln Gly Leu
810 815 820
gcc aag atc att cag aaa gct cat aag gaa gga gtg tgc ggt cta cga 2610
Ala Lys Ile Ile Gln Lys Ala His Lys Glu Gly Val Cys Gly Leu Arg
825 830 835
tca gtt tcc aga ctg gag cat caa atg tgg gaa gca gtg aag gac gag 2658
Ser Val Ser Arg Leu Glu His Gln Met Trp Glu Ala Val Lys Asp Glu
840 845 850
ctg aac act ctt ttg aag gag aat ggt gtg gac ctt agt gtc gtg gtt 2706
Leu Asn Thr Leu Leu Lys Glu Asn Gly Val Asp Leu Ser Val Val Val
855 860 865 870
gag aaa cag gag gga atg tac aag tca gca cct aaa cgc ctc acc gcc 2754
Glu Lys Gln Glu Gly Met Tyr Lys Ser Ala Pro Lys Arg Leu Thr Ala
875 880 885
acc acg gaa aaa ttg gaa att ggc tgg aag gcc tgg gga aag agt att 2802
Thr Thr Glu Lys Leu Glu Ile Gly Trp Lys Ala Trp Gly Lys Ser Ile
890 895 900
tta ttt gca cca gaa ctc gcc aac aac acc ttt gtg gtt gat ggt ccg 2850
Leu Phe Ala Pro Glu Leu Ala Asn Asn Thr Phe Val Val Asp Gly Pro
905 910 915
gag acc aag gaa tgt ccg act cag aat cgc gct tgg aat agc tta gaa 2898
Glu Thr Lys Glu Cys Pro Thr Gln Asn Arg Ala Trp Asn Ser Leu Glu
920 925 930
gtg gag gat ttt gga ttt ggt ctc acc agc act cgg atg ttc ctg aag 2946
Val Glu Asp Phe Gly Phe Gly Leu Thr Ser Thr Arg Met Phe Leu Lys
935 940 945 950
gtc aga gag agc aac aca act gaa tgt gac tcg aag atc att gga acg 2994
Val Arg Glu Ser Asn Thr Thr Glu Cys Asp Ser Lys Ile Ile Gly Thr
955 960 965
gct gtc aag aac aac ttg gcg atc cac agt gac ctg tcc tat tgg att 3042
Ala Val Lys Asn Asn Leu Ala Ile His Ser Asp Leu Ser Tyr Trp Ile
970 975 980
gaa agc agg ctc aat gat acg tgg aag ctt gaa agg gca gtt ctg ggt 3090
Glu Ser Arg Leu Asn Asp Thr Trp Lys Leu Glu Arg Ala Val Leu Gly
985 990 995
gaa gtc aaa tca tgt acg tgg cct gag acg cat acc ttg tgg ggc 3135
Glu Val Lys Ser Cys Thr Trp Pro Glu Thr His Thr Leu Trp Gly
1000 1005 1010
gat gga atc ctt gag agt gac ttg ata ata cca gtc aca ctg gcg 3180
Asp Gly Ile Leu Glu Ser Asp Leu Ile Ile Pro Val Thr Leu Ala
1015 1020 1025
gga cca cga agc aat cac aat cgg aga cct ggg tac aag aca caa 3225
Gly Pro Arg Ser Asn His Asn Arg Arg Pro Gly Tyr Lys Thr Gln
1030 1035 1040
aac cag ggc cca tgg gac gaa ggc cgg gta gag att gac ttc gat 3270
Asn Gln Gly Pro Trp Asp Glu Gly Arg Val Glu Ile Asp Phe Asp
1045 1050 1055
tac tgc cca gga act acg gtc acc ctg agt gag agc tgc gga cac 3315
Tyr Cys Pro Gly Thr Thr Val Thr Leu Ser Glu Ser Cys Gly His
1060 1065 1070
cgt gga cct gcc act cgc acc acc aca gag agc gga aag ttg ata 3360
Arg Gly Pro Ala Thr Arg Thr Thr Thr Glu Ser Gly Lys Leu Ile
1075 1080 1085
aca gat tgg tgc tgc agg agc tgc acc tta cca cca ctg cgc tac 3405
Thr Asp Trp Cys Cys Arg Ser Cys Thr Leu Pro Pro Leu Arg Tyr
1090 1095 1100
caa act gac agc ggc tgt tgg tat ggt atg gag atc aga cca cag 3450
Gln Thr Asp Ser Gly Cys Trp Tyr Gly Met Glu Ile Arg Pro Gln
1105 1110 1115
aga cat gat gaa aag acc ctc gtg cag tca caa gtg aat gct tat 3495
Arg His Asp Glu Lys Thr Leu Val Gln Ser Gln Val Asn Ala Tyr
1120 1125 1130
aat gct gat atg att gac cct ttt cag ttg ggc ctt ctg gtc gtg 3540
Asn Ala Asp Met Ile Asp Pro Phe Gln Leu Gly Leu Leu Val Val
1135 1140 1145
ttc ttg gcc acc cag gag gtc ctt cgc aag agg tgg aca gcc aag 3585
Phe Leu Ala Thr Gln Glu Val Leu Arg Lys Arg Trp Thr Ala Lys
1150 1155 1160
atc agc atg cca gct ata ctg att gct ctg cta gtc ctg gtg ttt 3630
Ile Ser Met Pro Ala Ile Leu Ile Ala Leu Leu Val Leu Val Phe
1165 1170 1175
ggg ggc att act tac act gat gtg tta cgc tat gtc atc ttg gtg 3675
Gly Gly Ile Thr Tyr Thr Asp Val Leu Arg Tyr Val Ile Leu Val
1180 1185 1190
ggg gca gct ttc gca gaa tct aat tcg gga gga gac gtg gta cac 3720
Gly Ala Ala Phe Ala Glu Ser Asn Ser Gly Gly Asp Val Val His
1195 1200 1205
ttg gcg ctc atg gcg acc ttc aag ata caa cca gtg ttt atg gtg 3765
Leu Ala Leu Met Ala Thr Phe Lys Ile Gln Pro Val Phe Met Val
1210 1215 1220
gca tcg ttt ctc aaa gcg aga tgg acc aac cag gag aac att ttg 3810
Ala Ser Phe Leu Lys Ala Arg Trp Thr Asn Gln Glu Asn Ile Leu
1225 1230 1235
ttg atg ttg gcg gct gtt ttc ttt caa atg gct tat tac gat gcc 3855
Leu Met Leu Ala Ala Val Phe Phe Gln Met Ala Tyr Tyr Asp Ala
1240 1245 1250
cgc caa att ctg ctc tgg gag atc cct gat gtg ttg aat tca ctg 3900
Arg Gln Ile Leu Leu Trp Glu Ile Pro Asp Val Leu Asn Ser Leu
1255 1260 1265
gcg gta gct tgg atg ata ctg aga gcc ata aca ttc aca acg aca 3945
Ala Val Ala Trp Met Ile Leu Arg Ala Ile Thr Phe Thr Thr Thr
1270 1275 1280
tca aac gtg gtt gtt ccg ctg cta gcc ctg cta aca ccc ggg ctg 3990
Ser Asn Val Val Val Pro Leu Leu Ala Leu Leu Thr Pro Gly Leu
1285 1290 1295
aga tgc ttg aat ctg gat gtg tac agg ata ctg ctg ttg atg gtc 4035
Arg Cys Leu Asn Leu Asp Val Tyr Arg Ile Leu Leu Leu Met Val
1300 1305 1310
gga ata ggc agc ttg atc agg gag aag agg agt gca gct gca aaa 4080
Gly Ile Gly Ser Leu Ile Arg Glu Lys Arg Ser Ala Ala Ala Lys
1315 1320 1325
aag aaa gga gca agt ctg cta tgc ttg gct cta gcc tca aca gga 4125
Lys Lys Gly Ala Ser Leu Leu Cys Leu Ala Leu Ala Ser Thr Gly
1330 1335 1340
ctt ttc aac ccc atg atc ctt gct gct gga ctg att gca tgt gat 4170
Leu Phe Asn Pro Met Ile Leu Ala Ala Gly Leu Ile Ala Cys Asp
1345 1350 1355
ccc aac cgt aaa cgc gga tgg ccc gca act gaa gtg atg aca gct 4215
Pro Asn Arg Lys Arg Gly Trp Pro Ala Thr Glu Val Met Thr Ala
1360 1365 1370
gtc ggc cta atg ttt gcc atc gtc gga ggg ctg gca gag ctt gac 4260
Val Gly Leu Met Phe Ala Ile Val Gly Gly Leu Ala Glu Leu Asp
1375 1380 1385
att gac tcc atg gcc att cca atg act atc gcg ggg ctc atg ttt 4305
Ile Asp Ser Met Ala Ile Pro Met Thr Ile Ala Gly Leu Met Phe
1390 1395 1400
gct gct ttc gtg att tct ggg aaa tca aca gat atg tgg att gag 4350
Ala Ala Phe Val Ile Ser Gly Lys Ser Thr Asp Met Trp Ile Glu
1405 1410 1415
aga acg gcg gac att tcc tgg gaa agt gat gca gaa att aca ggc 4395
Arg Thr Ala Asp Ile Ser Trp Glu Ser Asp Ala Glu Ile Thr Gly
1420 1425 1430
tcg agc gaa aga gtt gat gtg cgg ctt gat gat gat gga aac ttc 4440
Ser Ser Glu Arg Val Asp Val Arg Leu Asp Asp Asp Gly Asn Phe
1435 1440 1445
cag ctc atg aat gat cca gga gca cct tgg aag ata tgg atg ctc 4485
Gln Leu Met Asn Asp Pro Gly Ala Pro Trp Lys Ile Trp Met Leu
1450 1455 1460
aga atg gtc tgt ctc gcg att agt gcg tac acc ccc tgg gca atc 4530
Arg Met Val Cys Leu Ala Ile Ser Ala Tyr Thr Pro Trp Ala Ile
1465 1470 1475
ttg ccc tca gta gtt gga ttt tgg ata act ctc caa tac aca aag 4575
Leu Pro Ser Val Val Gly Phe Trp Ile Thr Leu Gln Tyr Thr Lys
1480 1485 1490
aga gga ggc gtg ttg tgg gac act ccc tca cca aag gag tac aaa 4620
Arg Gly Gly Val Leu Trp Asp Thr Pro Ser Pro Lys Glu Tyr Lys
1495 1500 1505
aag ggg gac acg acc acc ggc gtc tac agg atc atg act cgt ggg 4665
Lys Gly Asp Thr Thr Thr Gly Val Tyr Arg Ile Met Thr Arg Gly
1510 1515 1520
ctg ctc ggc agt tat caa gca gga gcg ggc gtg atg gtt gaa ggt 4710
Leu Leu Gly Ser Tyr Gln Ala Gly Ala Gly Val Met Val Glu Gly
1525 1530 1535
gtt ttc cac acc ctt tgg cat aca aca aaa gga gcc gct ttg atg 4755
Val Phe His Thr Leu Trp His Thr Thr Lys Gly Ala Ala Leu Met
1540 1545 1550
agc gga gag ggc cgc ctg gac cca tac tgg ggc agt gtc aag gag 4800
Ser Gly Glu Gly Arg Leu Asp Pro Tyr Trp Gly Ser Val Lys Glu
1555 1560 1565
gat cga ctt tgt tac gga gga ccc tgg aaa ttg cag cac aag tgg 4845
Asp Arg Leu Cys Tyr Gly Gly Pro Trp Lys Leu Gln His Lys Trp
1570 1575 1580
aac ggg cag gat gag gtg cag atg att gtg gtg gaa cct ggc agg 4890
Asn Gly Gln Asp Glu Val Gln Met Ile Val Val Glu Pro Gly Arg
1585 1590 1595
aac gtt aag aac gtc cag acg aaa cca ggg gtg ttc aaa aca cct 4935
Asn Val Lys Asn Val Gln Thr Lys Pro Gly Val Phe Lys Thr Pro
1600 1605 1610
gaa gga gaa atc ggg gcc gtg act ttg gac ttc ccc act gga aca 4980
Glu Gly Glu Ile Gly Ala Val Thr Leu Asp Phe Pro Thr Gly Thr
1615 1620 1625
tca ggc tca cca ata gtg gac aaa aac ggt gat gtg att ggg ctt 5025
Ser Gly Ser Pro Ile Val Asp Lys Asn Gly Asp Val Ile Gly Leu
1630 1635 1640
tat ggc aat gga gtc ata atg ccc aac ggc tca tac ata agc gcg 5070
Tyr Gly Asn Gly Val Ile Met Pro Asn Gly Ser Tyr Ile Ser Ala
1645 1650 1655
ata gtg cag ggt gaa agg atg gat gag cca atc cca gcc gga ttc 5115
Ile Val Gln Gly Glu Arg Met Asp Glu Pro Ile Pro Ala Gly Phe
1660 1665 1670
gaa cct gag atg ctg agg aaa aaa cag atc act gta ctg gat ctc 5160
Glu Pro Glu Met Leu Arg Lys Lys Gln Ile Thr Val Leu Asp Leu
1675 1680 1685
cat ccc ggc gcc ggt aaa aca agg agg att ctg cca cag atc atc 5205
His Pro Gly Ala Gly Lys Thr Arg Arg Ile Leu Pro Gln Ile Ile
1690 1695 1700
aaa gag gcc ata aac aga aga ctg aga aca gcc gtg cta gca cca 5250
Lys Glu Ala Ile Asn Arg Arg Leu Arg Thr Ala Val Leu Ala Pro
1705 1710 1715
acc agg gtt gtg gct gct gag atg gct gaa gca ctg aga gga ctg 5295
Thr Arg Val Val Ala Ala Glu Met Ala Glu Ala Leu Arg Gly Leu
1720 1725 1730
ccc atc cgg tac cag aca tcc gca gtg ccc aga gaa cat aat gga 5340
Pro Ile Arg Tyr Gln Thr Ser Ala Val Pro Arg Glu His Asn Gly
1735 1740 1745
aat gag att gtt gat gtc atg tgt cat gct acc ctc acc cac agg 5385
Asn Glu Ile Val Asp Val Met Cys His Ala Thr Leu Thr His Arg
1750 1755 1760
ctg atg tct cct cac agg gtg ccg aac tac aac ctg ttc gtg atg 5430
Leu Met Ser Pro His Arg Val Pro Asn Tyr Asn Leu Phe Val Met
1765 1770 1775
gat gag gct cat ttc acc gac cca gct agc att gca gca aga ggt 5475
Asp Glu Ala His Phe Thr Asp Pro Ala Ser Ile Ala Ala Arg Gly
1780 1785 1790
tac att tcc aca aag gtc gag cta ggg gag gcg gcg gca ata ttc 5520
Tyr Ile Ser Thr Lys Val Glu Leu Gly Glu Ala Ala Ala Ile Phe
1795 1800 1805
atg aca gcc acc cca cca ggc act tca gat cca ttc cca gag tcc 5565
Met Thr Ala Thr Pro Pro Gly Thr Ser Asp Pro Phe Pro Glu Ser
1810 1815 1820
aat tca cca att tcc gac tta cag act gag atc ccg gat cga gct 5610
Asn Ser Pro Ile Ser Asp Leu Gln Thr Glu Ile Pro Asp Arg Ala
1825 1830 1835
tgg aac tct gga tac gaa tgg atc aca gaa tac acc ggg aag acg 5655
Trp Asn Ser Gly Tyr Glu Trp Ile Thr Glu Tyr Thr Gly Lys Thr
1840 1845 1850
gtt tgg ttt gtg cct agt gtc aag atg ggg aat gag att gcc ctt 5700
Val Trp Phe Val Pro Ser Val Lys Met Gly Asn Glu Ile Ala Leu
1855 1860 1865
tgc cta caa cgt gct gga aag aaa gta gtc caa ttg aac aga aag 5745
Cys Leu Gln Arg Ala Gly Lys Lys Val Val Gln Leu Asn Arg Lys
1870 1875 1880
tcg tac gag acg gag tac cca aaa tgt aag aac gat gat tgg gac 5790
Ser Tyr Glu Thr Glu Tyr Pro Lys Cys Lys Asn Asp Asp Trp Asp
1885 1890 1895
ttt gtt atc aca aca gac ata tct gaa atg ggg gct aac ttc aag 5835
Phe Val Ile Thr Thr Asp Ile Ser Glu Met Gly Ala Asn Phe Lys
1900 1905 1910
gcg agc agg gtg att gac agc cgg aag agt gtg aaa cca acc atc 5880
Ala Ser Arg Val Ile Asp Ser Arg Lys Ser Val Lys Pro Thr Ile
1915 1920 1925
ata aca gaa gga gaa ggg aga gtg atc ctg gga gaa cca tct gca 5925
Ile Thr Glu Gly Glu Gly Arg Val Ile Leu Gly Glu Pro Ser Ala
1930 1935 1940
gtg aca gca gct agt gcc gcc cag aga cgt gga cgt atc ggt aga 5970
Val Thr Ala Ala Ser Ala Ala Gln Arg Arg Gly Arg Ile Gly Arg
1945 1950 1955
aat ccg tcg caa gtt ggt gat gag tac tgt tat ggg ggg cac acg 6015
Asn Pro Ser Gln Val Gly Asp Glu Tyr Cys Tyr Gly Gly His Thr
1960 1965 1970
aat gaa gac gac tcg aac ttc gcc cat tgg act gag gca cga atc 6060
Asn Glu Asp Asp Ser Asn Phe Ala His Trp Thr Glu Ala Arg Ile
1975 1980 1985
atg ctg gac aac atc aac atg cca aac gga ctg atc gct caa ttc 6105
Met Leu Asp Asn Ile Asn Met Pro Asn Gly Leu Ile Ala Gln Phe
1990 1995 2000
tac caa cca gag cgt gag aag gta tat acc atg gat ggg gaa tac 6150
Tyr Gln Pro Glu Arg Glu Lys Val Tyr Thr Met Asp Gly Glu Tyr
2005 2010 2015
cgg ctc aga gga gaa gag aga aaa aac ttt ctg gaa ctg ttg agg 6195
Arg Leu Arg Gly Glu Glu Arg Lys Asn Phe Leu Glu Leu Leu Arg
2020 2025 2030
act gca gat ctg cca gtt tgg ctg gct tac aag gtt gca gcg gct 6240
Thr Ala Asp Leu Pro Val Trp Leu Ala Tyr Lys Val Ala Ala Ala
2035 2040 2045
gga gtg tca tac cac gac cgg agg tgg tgc ttt gat ggt cct agg 6285
Gly Val Ser Tyr His Asp Arg Arg Trp Cys Phe Asp Gly Pro Arg
2050 2055 2060
aca aac aca att tta gaa gac aac aac gaa gtg gaa gtc atc acg 6330
Thr Asn Thr Ile Leu Glu Asp Asn Asn Glu Val Glu Val Ile Thr
2065 2070 2075
aag ctt ggt gaa agg aag att ctg agg ccg cgc tgg att gac gcc 6375
Lys Leu Gly Glu Arg Lys Ile Leu Arg Pro Arg Trp Ile Asp Ala
2080 2085 2090
agg gtg tac tcg gat cac cag gca cta aag gcg ttc aag gac ttc 6420
Arg Val Tyr Ser Asp His Gln Ala Leu Lys Ala Phe Lys Asp Phe
2095 2100 2105
gcc tcg gga aaa cgt tct cag ata ggg ctc att gag gtt ctg gga 6465
Ala Ser Gly Lys Arg Ser Gln Ile Gly Leu Ile Glu Val Leu Gly
2110 2115 2120
aag atg cct gag cac ttc atg ggg aag aca tgg gaa gca ctt gac 6510
Lys Met Pro Glu His Phe Met Gly Lys Thr Trp Glu Ala Leu Asp
2125 2130 2135
acc atg tac gtt gtg gcc act gca gag aaa gga gga aga gct cac 6555
Thr Met Tyr Val Val Ala Thr Ala Glu Lys Gly Gly Arg Ala His
2140 2145 2150
aga atg gcc ctg gag gaa ctg cca gat gct ctt cag aca att gcc 6600
Arg Met Ala Leu Glu Glu Leu Pro Asp Ala Leu Gln Thr Ile Ala
2155 2160 2165
ttg att gcc tta ttg agt gtg atg acc atg gga gta ttc ttc ctc 6645
Leu Ile Ala Leu Leu Ser Val Met Thr Met Gly Val Phe Phe Leu
2170 2175 2180
ctc atg cag cgg aag ggc att gga aag ata ggt ttg gga ggc gct 6690
Leu Met Gln Arg Lys Gly Ile Gly Lys Ile Gly Leu Gly Gly Ala
2185 2190 2195
gtc ttg gga gtc gcg acc ttt ttc tgt tgg atg gct gaa gtt cca 6735
Val Leu Gly Val Ala Thr Phe Phe Cys Trp Met Ala Glu Val Pro
2200 2205 2210
gga acg aag atc gcc gga atg ttg ctg ctc tcc ctt ctc ttg atg 6780
Gly Thr Lys Ile Ala Gly Met Leu Leu Leu Ser Leu Leu Leu Met
2215 2220 2225
att gtg cta att cct gag cca gag aag caa cgt tcg cag aca gac 6825
Ile Val Leu Ile Pro Glu Pro Glu Lys Gln Arg Ser Gln Thr Asp
2230 2235 2240
aac cag cta gcc gtg ttc ctg att tgt gtc atg acc ctt gtg agc 6870
Asn Gln Leu Ala Val Phe Leu Ile Cys Val Met Thr Leu Val Ser
2245 2250 2255
gca gtg gca gcc aac gag atg ggt tgg cta gat aag acc aag agt 6915
Ala Val Ala Ala Asn Glu Met Gly Trp Leu Asp Lys Thr Lys Ser
2260 2265 2270
gac ata agc agt ttg ttt ggg caa aga att gag gtc aag gag aat 6960
Asp Ile Ser Ser Leu Phe Gly Gln Arg Ile Glu Val Lys Glu Asn
2275 2280 2285
ttc agc atg gga gag ttt ctt ttg gac ttg agg cct gca aca gcc 7005
Phe Ser Met Gly Glu Phe Leu Leu Asp Leu Arg Pro Ala Thr Ala
2290 2295 2300
tgg tca ctg tac gct gtg aca aca gcg gtc ctc act cca ctg cta 7050
Trp Ser Leu Tyr Ala Val Thr Thr Ala Val Leu Thr Pro Leu Leu
2305 2310 2315
aag cat ttg atc acg tca gat tac atc aac acc tca ttg acc tca 7095
Lys His Leu Ile Thr Ser Asp Tyr Ile Asn Thr Ser Leu Thr Ser
2320 2325 2330
ata aac gtt cag gca agt gca cta ttc aca ctc gcg cga ggc ttc 7140
Ile Asn Val Gln Ala Ser Ala Leu Phe Thr Leu Ala Arg Gly Phe
2335 2340 2345
ccc ttc gtc gat gtt gga gtg tcg gct ctc ctg cta gca gcc gga 7185
Pro Phe Val Asp Val Gly Val Ser Ala Leu Leu Leu Ala Ala Gly
2350 2355 2360
tgc tgg gga caa gtc acc ctc acc gtt acg gta aca gcg gca aca 7230
Cys Trp Gly Gln Val Thr Leu Thr Val Thr Val Thr Ala Ala Thr
2365 2370 2375
ctc ctt ttt tgc cac tat gcc tac atg gtt ccc ggt tgg caa gct 7275
Leu Leu Phe Cys His Tyr Ala Tyr Met Val Pro Gly Trp Gln Ala
2380 2385 2390
gag gca atg cgc tca gcc cag cgg cgg aca gcg gcc gga atc atg 7320
Glu Ala Met Arg Ser Ala Gln Arg Arg Thr Ala Ala Gly Ile Met
2395 2400 2405
aag aac gct gta gtg gat ggc atc gtg gcc acg gac gtc cca gaa 7365
Lys Asn Ala Val Val Asp Gly Ile Val Ala Thr Asp Val Pro Glu
2410 2415 2420
tta gag cgc acc aca ccc atc atg cag aag aaa gtt gga cag atc 7410
Leu Glu Arg Thr Thr Pro Ile Met Gln Lys Lys Val Gly Gln Ile
2425 2430 2435
atg ctg atc ttg gtg tct cta gct gca gta gta gtg aac ccg tct 7455
Met Leu Ile Leu Val Ser Leu Ala Ala Val Val Val Asn Pro Ser
2440 2445 2450
gtg aag aca gta cga gaa gcc gga att ttg atc acg gcc gca gcg 7500
Val Lys Thr Val Arg Glu Ala Gly Ile Leu Ile Thr Ala Ala Ala
2455 2460 2465
gtg acg ctt tgg gag aat gga gca agc tct gtt tgg aac gca aca 7545
Val Thr Leu Trp Glu Asn Gly Ala Ser Ser Val Trp Asn Ala Thr
2470 2475 2480
act gcc atc gga ctc tgc cac atc atg cgt ggg ggt tgg ttg tca 7590
Thr Ala Ile Gly Leu Cys His Ile Met Arg Gly Gly Trp Leu Ser
2485 2490 2495
tgt cta tcc ata aca tgg aca ctc ata aag aac atg gaa aaa cca 7635
Cys Leu Ser Ile Thr Trp Thr Leu Ile Lys Asn Met Glu Lys Pro
2500 2505 2510
gga cta aaa aga ggt ggg gca aaa gga cgc acc ttg gga gag gtt 7680
Gly Leu Lys Arg Gly Gly Ala Lys Gly Arg Thr Leu Gly Glu Val
2515 2520 2525
tgg aaa gaa aga ctc aac cag atg aca aaa gaa gag ttc act agg 7725
Trp Lys Glu Arg Leu Asn Gln Met Thr Lys Glu Glu Phe Thr Arg
2530 2535 2540
tac cgc aaa gag gcc atc atc gaa gtc gat cgc tca gcg gca aaa 7770
Tyr Arg Lys Glu Ala Ile Ile Glu Val Asp Arg Ser Ala Ala Lys
2545 2550 2555
cac gcc agg aaa gaa ggc aat gtc act gga ggg cat cca gtc tct 7815
His Ala Arg Lys Glu Gly Asn Val Thr Gly Gly His Pro Val Ser
2560 2565 2570
agg ggc aca gca aaa ctg aga tgg ctg gtc gaa cgg agg ttt ctc 7860
Arg Gly Thr Ala Lys Leu Arg Trp Leu Val Glu Arg Arg Phe Leu
2575 2580 2585
gaa ccg gtc gga aaa gtg att gac ctt gga tgt gga aga ggc ggt 7905
Glu Pro Val Gly Lys Val Ile Asp Leu Gly Cys Gly Arg Gly Gly
2590 2595 2600
tgg tgt tac tat atg gca acc caa aaa aga gtc caa gaa gtc aga 7950
Trp Cys Tyr Tyr Met Ala Thr Gln Lys Arg Val Gln Glu Val Arg
2605 2610 2615
ggg tac aca aag ggc ggt ccc gga cat gaa gag ccc caa cta gtg 7995
Gly Tyr Thr Lys Gly Gly Pro Gly His Glu Glu Pro Gln Leu Val
2620 2625 2630
caa agt tat gga tgg aac att gtc acc atg aag agt gga gtg gat 8040
Gln Ser Tyr Gly Trp Asn Ile Val Thr Met Lys Ser Gly Val Asp
2635 2640 2645
gtg ttc tac aga cct tct gag tgt tgt gac acc ctc ctt tgt gac 8085
Val Phe Tyr Arg Pro Ser Glu Cys Cys Asp Thr Leu Leu Cys Asp
2650 2655 2660
atc gga gag tcc tcg tca agt gct gag gtt gaa gag cat agg acg 8130
Ile Gly Glu Ser Ser Ser Ser Ala Glu Val Glu Glu His Arg Thr
2665 2670 2675
att cgg gtc ctt gaa atg gtt gag gac tgg ctg cac cga ggg cca 8175
Ile Arg Val Leu Glu Met Val Glu Asp Trp Leu His Arg Gly Pro
2680 2685 2690
agg gaa ttt tgc gtg aag gtg ctc tgc ccc tac atg ccg aaa gtc 8220
Arg Glu Phe Cys Val Lys Val Leu Cys Pro Tyr Met Pro Lys Val
2695 2700 2705
ata gag aag atg gag ctg ctc caa cgc cgg tat ggg ggg gga ctg 8265
Ile Glu Lys Met Glu Leu Leu Gln Arg Arg Tyr Gly Gly Gly Leu
2710 2715 2720
gtc aga aac cca ctc tca cgg aat tcc acg cac gag atg tat tgg 8310
Val Arg Asn Pro Leu Ser Arg Asn Ser Thr His Glu Met Tyr Trp
2725 2730 2735
gtg agt cga gct tca ggc aat gtg gta cat tca gtg aat atg acc 8355
Val Ser Arg Ala Ser Gly Asn Val Val His Ser Val Asn Met Thr
2740 2745 2750
agc cag gtg ctc cta gga aga atg gaa aaa agg acc tgg aag gga 8400
Ser Gln Val Leu Leu Gly Arg Met Glu Lys Arg Thr Trp Lys Gly
2755 2760 2765
ccc caa tac gag gaa gat gta aac ttg gga agt gga acc agg gcg 8445
Pro Gln Tyr Glu Glu Asp Val Asn Leu Gly Ser Gly Thr Arg Ala
2770 2775 2780
gtg gga aaa ccc ctg ctc aac tca gac acc agt aaa atc aag aac 8490
Val Gly Lys Pro Leu Leu Asn Ser Asp Thr Ser Lys Ile Lys Asn
2785 2790 2795
agg att gaa cga ctc agg cgt gag tac agt tcg acg tgg cac cac 8535
Arg Ile Glu Arg Leu Arg Arg Glu Tyr Ser Ser Thr Trp His His
2800 2805 2810
gat gag aac cac cca tat aga acc tgg aac tat cac ggc agt tat 8580
Asp Glu Asn His Pro Tyr Arg Thr Trp Asn Tyr His Gly Ser Tyr
2815 2820 2825
gat gtg aag ccc aca ggc tcc gcc agt tcg ctg gtc aat gga gtg 8625
Asp Val Lys Pro Thr Gly Ser Ala Ser Ser Leu Val Asn Gly Val
2830 2835 2840
gtc agg ctc ctc tca aaa cca tgg gac acc atc acg aat gtt acc 8670
Val Arg Leu Leu Ser Lys Pro Trp Asp Thr Ile Thr Asn Val Thr
2845 2850 2855
acc atg gcc atg act gac act act ccc ttc ggg cag cag cga gtg 8715
Thr Met Ala Met Thr Asp Thr Thr Pro Phe Gly Gln Gln Arg Val
2860 2865 2870
ttc aaa gag aag gtg gac acg aaa gct cct gaa ccg cca gaa gga 8760
Phe Lys Glu Lys Val Asp Thr Lys Ala Pro Glu Pro Pro Glu Gly
2875 2880 2885
gtg aag tac gtg ctc aac gag acc acc aac tgg ttg tgg gcg ttt 8805
Val Lys Tyr Val Leu Asn Glu Thr Thr Asn Trp Leu Trp Ala Phe
2890 2895 2900
ttg gcc aga gaa aaa cgt ccc aga atg tgc tct cga gag gaa ttc 8850
Leu Ala Arg Glu Lys Arg Pro Arg Met Cys Ser Arg Glu Glu Phe
2905 2910 2915
ata aga aag gtc aac agc aat gca gct ttg ggt gcc atg ttt gaa 8895
Ile Arg Lys Val Asn Ser Asn Ala Ala Leu Gly Ala Met Phe Glu
2920 2925 2930
gag cag aat caa tgg agg agc gcc aga gaa gca gtt gaa gat cca 8940
Glu Gln Asn Gln Trp Arg Ser Ala Arg Glu Ala Val Glu Asp Pro
2935 2940 2945
aaa ttt tgg gag atg gtg gat gag gag cgc gag gca cat ctg cgg 8985
Lys Phe Trp Glu Met Val Asp Glu Glu Arg Glu Ala His Leu Arg
2950 2955 2960
ggg gaa tgt cac act tgc att tac aac atg atg gga aag aga gag 9030
Gly Glu Cys His Thr Cys Ile Tyr Asn Met Met Gly Lys Arg Glu
2965 2970 2975
aaa aaa ccc gga gag ttc gga aag gcc aag gga agc aga gcc att 9075
Lys Lys Pro Gly Glu Phe Gly Lys Ala Lys Gly Ser Arg Ala Ile
2980 2985 2990
tgg ttc atg tgg ctc gga gct cgc ttt ctg gag ttc gag gct ctg 9120
Trp Phe Met Trp Leu Gly Ala Arg Phe Leu Glu Phe Glu Ala Leu
2995 3000 3005
ggt ttt ctc aat gaa gac cac tgg ctt gga aga aag aac tca gga 9165
Gly Phe Leu Asn Glu Asp His Trp Leu Gly Arg Lys Asn Ser Gly
3010 3015 3020
gga ggt gtc gag ggc ttg ggc ctc caa aaa ctg ggt tac atc ctg 9210
Gly Gly Val Glu Gly Leu Gly Leu Gln Lys Leu Gly Tyr Ile Leu
3025 3030 3035
cgt gaa gtt ggc acc cgg cct ggg ggc aag atc tat gct gat gac 9255
Arg Glu Val Gly Thr Arg Pro Gly Gly Lys Ile Tyr Ala Asp Asp
3040 3045 3050
aca gct ggc tgg gac acc cgc atc acg aga gct gac ttg gaa aat 9300
Thr Ala Gly Trp Asp Thr Arg Ile Thr Arg Ala Asp Leu Glu Asn
3055 3060 3065
gaa gct aag gtg ctt gag ctg ctt gat ggg gaa cat cgg cgt ctt 9345
Glu Ala Lys Val Leu Glu Leu Leu Asp Gly Glu His Arg Arg Leu
3070 3075 3080
gcc agg gcc atc att gag ctc acc tat cgt cac aaa gtt gtg aaa 9390
Ala Arg Ala Ile Ile Glu Leu Thr Tyr Arg His Lys Val Val Lys
3085 3090 3095
gtg atg cgc ccg gct gct gat gga aga acc gtc atg gat gtt atc 9435
Val Met Arg Pro Ala Ala Asp Gly Arg Thr Val Met Asp Val Ile
3100 3105 3110
tcc aga gaa gat cag agg ggg agt gga caa gtt gtc acc tac gcc 9480
Ser Arg Glu Asp Gln Arg Gly Ser Gly Gln Val Val Thr Tyr Ala
3115 3120 3125
cta aac act ttc acc aac ctg gcc gtc cag ctg gtg agg atg atg 9525
Leu Asn Thr Phe Thr Asn Leu Ala Val Gln Leu Val Arg Met Met
3130 3135 3140
gaa ggg gaa gga gtg att ggc cca gat gat gtg gag aaa ctc aca 9570
Glu Gly Glu Gly Val Ile Gly Pro Asp Asp Val Glu Lys Leu Thr
3145 3150 3155
aaa ggg aaa gga ccc aaa gtc agg acc tgg ctg ttt gag aat ggg 9615
Lys Gly Lys Gly Pro Lys Val Arg Thr Trp Leu Phe Glu Asn Gly
3160 3165 3170
gaa gaa aga ctc agc cgc atg gct gtc agt gga gat gac tgt gtg 9660
Glu Glu Arg Leu Ser Arg Met Ala Val Ser Gly Asp Asp Cys Val
3175 3180 3185
gta aag ccc ctg gac gat cgc ttt gcc acc tcg ctc cac ttc ctc 9705
Val Lys Pro Leu Asp Asp Arg Phe Ala Thr Ser Leu His Phe Leu
3190 3195 3200
aat gct atg tca aag gtt cgc aaa gac atc caa gag tgg aaa ccg 9750
Asn Ala Met Ser Lys Val Arg Lys Asp Ile Gln Glu Trp Lys Pro
3205 3210 3215
tca act gga tgg tat gat tgg cag cag gtt cca ttt tgc tca aac 9795
Ser Thr Gly Trp Tyr Asp Trp Gln Gln Val Pro Phe Cys Ser Asn
3220 3225 3230
cat ttc act gaa ttg atc atg aaa gat gga aga aca ctg gtg gtt 9840
His Phe Thr Glu Leu Ile Met Lys Asp Gly Arg Thr Leu Val Val
3235 3240 3245
cca tgc cga gga cag gat gaa ttg gta ggc aga gct cgc ata tct 9885
Pro Cys Arg Gly Gln Asp Glu Leu Val Gly Arg Ala Arg Ile Ser
3250 3255 3260
cca ggg gcc gga tgg aac gtc cgc gac act gct tgt ctg gct aag 9930
Pro Gly Ala Gly Trp Asn Val Arg Asp Thr Ala Cys Leu Ala Lys
3265 3270 3275
tct tat gcc cag atg tgg ctg ctt ctg tac ttc cac aga aga gac 9975
Ser Tyr Ala Gln Met Trp Leu Leu Leu Tyr Phe His Arg Arg Asp
3280 3285 3290
ctg cgg ctc atg gcc aac gcc att tgc tcc gct gtc cct gtg aat 10020
Leu Arg Leu Met Ala Asn Ala Ile Cys Ser Ala Val Pro Val Asn
3295 3300 3305
tgg gtc cct acc gga aga acc acg tgg tcc atc cat gca gga gga 10065
Trp Val Pro Thr Gly Arg Thr Thr Trp Ser Ile His Ala Gly Gly
3310 3315 3320
gag tgg atg aca aca gag gac atg ttg gag gtc tgg aac cgt gtt 10110
Glu Trp Met Thr Thr Glu Asp Met Leu Glu Val Trp Asn Arg Val
3325 3330 3335
tgg ata gag gag aat gaa tgg atg gaa gac aaa acc cca gtg gag 10155
Trp Ile Glu Glu Asn Glu Trp Met Glu Asp Lys Thr Pro Val Glu
3340 3345 3350
aaa tgg agt gac gtc cca tat tca gga aaa cga gag gac atc tgg 10200
Lys Trp Ser Asp Val Pro Tyr Ser Gly Lys Arg Glu Asp Ile Trp
3355 3360 3365
tgt ggc agc ctg att ggc aca aga gcc cga gcc acg tgg gca gaa 10245
Cys Gly Ser Leu Ile Gly Thr Arg Ala Arg Ala Thr Trp Ala Glu
3370 3375 3380
aac atc cag gtg gct atc aac caa gtc aga gca atc atc gga gat 10290
Asn Ile Gln Val Ala Ile Asn Gln Val Arg Ala Ile Ile Gly Asp
3385 3390 3395
gag aag tat gtg gat tac atg agt tca cta aag aga tat gaa gac 10335
Glu Lys Tyr Val Asp Tyr Met Ser Ser Leu Lys Arg Tyr Glu Asp
3400 3405 3410
aca act ttg gtt gag gac aca gta ctg tag atatttaatc aattgtaaat 10385
Thr Thr Leu Val Glu Asp Thr Val Leu
3415 3420
agacaatata agtatgcata aaagtgtagt tttatagtag tatttagtgg tgttagtgta10445
aatagttaag aaaattttga ggagaaagtc aggccgggaa gttcccgcca ccggaagttg10505
agtagacggt gctgcctgcg actcaacccc aggaggactg ggtgaacaaa gccgcgaagt10565
gatccatgta agccctcaga accgtctcgg aaggaggacc ccacatgttg taacttcaaa10625
gcccaatgtc agaccacgct acggcgtgct actctgcgga gagtgcagtc tgcgatagtg10685
ccccaggagg actgggttaa caaaggcaaa ccaacgcccc acgcggccct agccccggta10745
atggtgttaa ccagggcgaa aggactagag gttagaggag accccgcggt ttaaagtgca10805
cggcccagcc tggctgaagc tgtaggtcag gggaaggact agaggttagt ggagaccccg10865
tgccacaaaa caccacaaca aaacagcata ttgacacctg ggatagacta ggagatcttc10925
tgctctgcac aaccagccac acggcacagt gcgccgacaa tggtggctgg tggtgcgaga10985
acacaggatc t 10996
<210> 12
<211> 3422
<212> PRT
<213> 人工序列
<220>
<223> 合成的构建体
<400> 12
Met Ser Lys Lys Pro Gly Gly Pro Gly Lys Ser Arg Ala Val Asn Met
1 5 10 15
Leu Lys Arg Gly Met Pro Arg Val Leu Ser Leu Ile Gly Leu Lys Arg
20 25 30
Ala Met Leu Ser Leu Ile Asp Gly Lys Gly Pro Ile Arg Phe Val Leu
35 40 45
Ala Leu Leu Ala Phe Phe Arg Phe Thr Ala Ile Ala Pro Thr Arg Ala
50 55 60
Val Leu Asp Arg Trp Arg Gly Val Asn Lys Gln Thr Ala Met Lys His
65 70 75 80
Leu Leu Ser Phe Lys Lys Glu Leu Gly Thr Leu Thr Ser Ala Ile Asn
85 90 95
Arg Arg Ser Ser Lys Gln Lys Lys Arg Ser Val Thr Met Leu Leu Met
100 105 110
Leu Leu Pro Thr Ala Leu Ala Phe His Leu Thr Thr Arg Gly Gly Glu
115 120 125
Pro His Met Ile Val Ser Lys Gln Glu Arg Gly Lys Ser Leu Leu Phe
130 135 140
Lys Thr Ser Ala Gly Val Asn Met Cys Thr Leu Ile Ala Met Asp Leu
145 150 155 160
Gly Glu Leu Cys Glu Asp Thr Met Thr Tyr Lys Cys Pro Arg Ile Thr
165 170 175
Glu Ala Glu Pro Asp Asp Val Asp Cys Trp Cys Asn Ala Thr Asp Thr
180 185 190
Trp Val Thr Tyr Gly Thr Cys Ser Gln Thr Gly Glu His Arg Arg Asp
195 200 205
Lys Arg Ser Val Ala Leu Ala Pro His Val Gly Leu Gly Leu Glu Thr
210 215 220
Arg Ala Glu Thr Trp Met Ser Ser Glu Gly Ala Trp Lys Gln Ile Gln
225 230 235 240
Lys Val Glu Thr Trp Ala Leu Arg His Pro Gly Phe Thr Val Ile Ala
245 250 255
Leu Phe Leu Ala His Ala Ile Gly Thr Ser Ile Thr Gln Lys Gly Ile
260 265 270
Ile Phe Ile Leu Leu Met Leu Val Thr Pro Ser Met Ala Met Arg Cys
275 280 285
Val Gly Ile Gly Asn Arg Asp Phe Val Glu Gly Leu Ser Gly Ala Thr
290 295 300
Trp Val Asp Val Val Leu Glu His Gly Ser Cys Val Thr Thr Met Ala
305 310 315 320
Lys Asn Lys Pro Thr Leu Asp Ile Glu Leu Leu Lys Thr Glu Val Thr
325 330 335
Asn Pro Ala Val Leu Arg Lys Leu Cys Ile Glu Ala Lys Ile Ser Asn
340 345 350
Thr Thr Thr Asp Ser Arg Cys Pro Thr Gln Gly Glu Ala Thr Leu Val
355 360 365
Glu Glu Gln Asp Ala Asn Phe Val Cys Arg Arg Thr Phe Val Asp Arg
370 375 380
Gly Trp Gly Asn Gly Cys Gly Leu Phe Gly Lys Gly Ser Leu Ile Thr
385 390 395 400
Cys Ala Lys Phe Lys Cys Val Thr Lys Leu Glu Gly Lys Ile Val Gln
405 410 415
Tyr Glu Asn Leu Lys Tyr Ser Val Ile Val Thr Val His Thr Gly Asp
420 425 430
Gln His Gln Val Gly Asn Glu Thr Thr Glu His Gly Thr Thr Ala Thr
435 440 445
Ile Thr Pro Gln Ala Pro Thr Ser Glu Ile Gln Leu Thr Asp Tyr Gly
450 455 460
Thr Leu Thr Leu Asp Cys Ser Pro Arg Thr Gly Leu Asp Phe Asn Glu
465 470 475 480
Met Val Leu Leu Thr Met Lys Glu Arg Ser Trp Leu Val His Lys Gln
485 490 495
Trp Phe Leu Asp Leu Pro Leu Pro Trp Thr Ser Gly Ala Ser Thr Ser
500 505 510
Gln Glu Thr Trp Asn Arg Gln Asp Leu Leu Val Thr Phe Lys Thr Ala
515 520 525
His Ala Lys Lys Gln Glu Val Val Val Leu Gly Ser Gln Glu Gly Ala
530 535 540
Met His Thr Ala Leu Thr Gly Ala Thr Glu Ile Gln Thr Ser Gly Thr
545 550 555 560
Thr Thr Ile Phe Ala Gly His Leu Lys Cys Arg Leu Lys Met Asp Lys
565 570 575
Leu Thr Leu Lys Gly Met Ser Tyr Val Met Cys Thr Gly Ser Phe Lys
580 585 590
Leu Glu Lys Glu Val Ala Glu Thr Gln His Gly Thr Val Leu Val Gln
595 600 605
Val Lys Tyr Glu Gly Thr Asp Ala Pro Cys Lys Ile Pro Phe Ser Thr
610 615 620
Gln Asp Glu Lys Gly Ala Thr Gln Asn Gly Arg Leu Ile Thr Ala Asn
625 630 635 640
Pro Ile Val Thr Asp Lys Glu Lys Pro Val Asn Ile Glu Ala Glu Pro
645 650 655
Pro Phe Gly Glu Ser Tyr Ile Val Val Gly Ala Gly Glu Lys Ala Leu
660 665 670
Lys Leu Ser Trp Phe Lys Lys Gly Ser Ser Ile Gly Lys Met Phe Glu
675 680 685
Ala Thr Ala Arg Gly Ala Arg Arg Met Ala Ile Leu Gly Asp Thr Ala
690 695 700
Trp Asp Phe Gly Ser Ile Gly Gly Val Phe Thr Ser Met Gly Lys Leu
705 710 715 720
Val His Gln Val Phe Gly Thr Ala Tyr Gly Val Leu Phe Ser Gly Val
725 730 735
Ser Trp Thr Met Lys Ile Gly Ile Gly Ile Leu Leu Thr Trp Leu Gly
740 745 750
Leu Asn Ser Arg Asn Thr Ser Leu Ser Met Met Cys Ile Ala Val Gly
755 760 765
Met Val Thr Leu Tyr Leu Gly Val Met Val Gln Ala Asp Ser Gly Cys
770 775 780
Ala Ile Asp Ile Ser Arg Gln Glu Leu Arg Cys Gly Ser Gly Val Phe
785 790 795 800
Ile His Asn Asp Val Glu Ala Trp Met Asp Arg Tyr Lys Tyr Tyr Pro
805 810 815
Glu Thr Pro Gln Gly Leu Ala Lys Ile Ile Gln Lys Ala His Lys Glu
820 825 830
Gly Val Cys Gly Leu Arg Ser Val Ser Arg Leu Glu His Gln Met Trp
835 840 845
Glu Ala Val Lys Asp Glu Leu Asn Thr Leu Leu Lys Glu Asn Gly Val
850 855 860
Asp Leu Ser Val Val Val Glu Lys Gln Glu Gly Met Tyr Lys Ser Ala
865 870 875 880
Pro Lys Arg Leu Thr Ala Thr Thr Glu Lys Leu Glu Ile Gly Trp Lys
885 890 895
Ala Trp Gly Lys Ser Ile Leu Phe Ala Pro Glu Leu Ala Asn Asn Thr
900 905 910
Phe Val Val Asp Gly Pro Glu Thr Lys Glu Cys Pro Thr Gln Asn Arg
915 920 925
Ala Trp Asn Ser Leu Glu Val Glu Asp Phe Gly Phe Gly Leu Thr Ser
930 935 940
Thr Arg Met Phe Leu Lys Val Arg Glu Ser Asn Thr Thr Glu Cys Asp
945 950 955 960
Ser Lys Ile Ile Gly Thr Ala Val Lys Asn Asn Leu Ala Ile His Ser
965 970 975
Asp Leu Ser Tyr Trp Ile Glu Ser Arg Leu Asn Asp Thr Trp Lys Leu
980 985 990
Glu Arg Ala Val Leu Gly Glu Val Lys Ser Cys Thr Trp Pro Glu Thr
995 1000 1005
His Thr Leu Trp Gly Asp Gly Ile Leu Glu Ser Asp Leu Ile Ile
1010 1015 1020
Pro Val Thr Leu Ala Gly Pro Arg Ser Asn His Asn Arg Arg Pro
1025 1030 1035
Gly Tyr Lys Thr Gln Asn Gln Gly Pro Trp Asp Glu Gly Arg Val
1040 1045 1050
Glu Ile Asp Phe Asp Tyr Cys Pro Gly Thr Thr Val Thr Leu Ser
1055 1060 1065
Glu Ser Cys Gly His Arg Gly Pro Ala Thr Arg Thr Thr Thr Glu
1070 1075 1080
Ser Gly Lys Leu Ile Thr Asp Trp Cys Cys Arg Ser Cys Thr Leu
1085 1090 1095
Pro Pro Leu Arg Tyr Gln Thr Asp Ser Gly Cys Trp Tyr Gly Met
1100 1105 1110
Glu Ile Arg Pro Gln Arg His Asp Glu Lys Thr Leu Val Gln Ser
1115 1120 1125
Gln Val Asn Ala Tyr Asn Ala Asp Met Ile Asp Pro Phe Gln Leu
1130 1135 1140
Gly Leu Leu Val Val Phe Leu Ala Thr Gln Glu Val Leu Arg Lys
1145 1150 1155
Arg Trp Thr Ala Lys Ile Ser Met Pro Ala Ile Leu Ile Ala Leu
1160 1165 1170
Leu Val Leu Val Phe Gly Gly Ile Thr Tyr Thr Asp Val Leu Arg
1175 1180 1185
Tyr Val Ile Leu Val Gly Ala Ala Phe Ala Glu Ser Asn Ser Gly
1190 1195 1200
Gly Asp Val Val His Leu Ala Leu Met Ala Thr Phe Lys Ile Gln
1205 1210 1215
Pro Val Phe Met Val Ala Ser Phe Leu Lys Ala Arg Trp Thr Asn
1220 1225 1230
Gln Glu Asn Ile Leu Leu Met Leu Ala Ala Val Phe Phe Gln Met
1235 1240 1245
Ala Tyr Tyr Asp Ala Arg Gln Ile Leu Leu Trp Glu Ile Pro Asp
1250 1255 1260
Val Leu Asn Ser Leu Ala Val Ala Trp Met Ile Leu Arg Ala Ile
1265 1270 1275
Thr Phe Thr Thr Thr Ser Asn Val Val Val Pro Leu Leu Ala Leu
1280 1285 1290
Leu Thr Pro Gly Leu Arg Cys Leu Asn Leu Asp Val Tyr Arg Ile
1295 1300 1305
Leu Leu Leu Met Val Gly Ile Gly Ser Leu Ile Arg Glu Lys Arg
1310 1315 1320
Ser Ala Ala Ala Lys Lys Lys Gly Ala Ser Leu Leu Cys Leu Ala
1325 1330 1335
Leu Ala Ser Thr Gly Leu Phe Asn Pro Met Ile Leu Ala Ala Gly
1340 1345 1350
Leu Ile Ala Cys Asp Pro Asn Arg Lys Arg Gly Trp Pro Ala Thr
1355 1360 1365
Glu Val Met Thr Ala Val Gly Leu Met Phe Ala Ile Val Gly Gly
1370 1375 1380
Leu Ala Glu Leu Asp Ile Asp Ser Met Ala Ile Pro Met Thr Ile
1385 1390 1395
Ala Gly Leu Met Phe Ala Ala Phe Val Ile Ser Gly Lys Ser Thr
1400 1405 1410
Asp Met Trp Ile Glu Arg Thr Ala Asp Ile Ser Trp Glu Ser Asp
1415 1420 1425
Ala Glu Ile Thr Gly Ser Ser Glu Arg Val Asp Val Arg Leu Asp
1430 1435 1440
Asp Asp Gly Asn Phe Gln Leu Met Asn Asp Pro Gly Ala Pro Trp
1445 1450 1455
Lys Ile Trp Met Leu Arg Met Val Cys Leu Ala Ile Ser Ala Tyr
1460 1465 1470
Thr Pro Trp Ala Ile Leu Pro Ser Val Val Gly Phe Trp Ile Thr
1475 1480 1485
Leu Gln Tyr Thr Lys Arg Gly Gly Val Leu Trp Asp Thr Pro Ser
1490 1495 1500
Pro Lys Glu Tyr Lys Lys Gly Asp Thr Thr Thr Gly Val Tyr Arg
1505 1510 1515
Ile Met Thr Arg Gly Leu Leu Gly Ser Tyr Gln Ala Gly Ala Gly
1520 1525 1530
Val Met Val Glu Gly Val Phe His Thr Leu Trp His Thr Thr Lys
1535 1540 1545
Gly Ala Ala Leu Met Ser Gly Glu Gly Arg Leu Asp Pro Tyr Trp
1550 1555 1560
Gly Ser Val Lys Glu Asp Arg Leu Cys Tyr Gly Gly Pro Trp Lys
1565 1570 1575
Leu Gln His Lys Trp Asn Gly Gln Asp Glu Val Gln Met Ile Val
1580 1585 1590
Val Glu Pro Gly Arg Asn Val Lys Asn Val Gln Thr Lys Pro Gly
1595 1600 1605
Val Phe Lys Thr Pro Glu Gly Glu Ile Gly Ala Val Thr Leu Asp
1610 1615 1620
Phe Pro Thr Gly Thr Ser Gly Ser Pro Ile Val Asp Lys Asn Gly
1625 1630 1635
Asp Val Ile Gly Leu Tyr Gly Asn Gly Val Ile Met Pro Asn Gly
1640 1645 1650
Ser Tyr Ile Ser Ala Ile Val Gln Gly Glu Arg Met Asp Glu Pro
1655 1660 1665
Ile Pro Ala Gly Phe Glu Pro Glu Met Leu Arg Lys Lys Gln Ile
1670 1675 1680
Thr Val Leu Asp Leu His Pro Gly Ala Gly Lys Thr Arg Arg Ile
1685 1690 1695
Leu Pro Gln Ile Ile Lys Glu Ala Ile Asn Arg Arg Leu Arg Thr
1700 1705 1710
Ala Val Leu Ala Pro Thr Arg Val Val Ala Ala Glu Met Ala Glu
1715 1720 1725
Ala Leu Arg Gly Leu Pro Ile Arg Tyr Gln Thr Ser Ala Val Pro
1730 1735 1740
Arg Glu His Asn Gly Asn Glu Ile Val Asp Val Met Cys His Ala
1745 1750 1755
Thr Leu Thr His Arg Leu Met Ser Pro His Arg Val Pro Asn Tyr
1760 1765 1770
Asn Leu Phe Val Met Asp Glu Ala His Phe Thr Asp Pro Ala Ser
1775 1780 1785
Ile Ala Ala Arg Gly Tyr Ile Ser Thr Lys Val Glu Leu Gly Glu
1790 1795 1800
Ala Ala Ala Ile Phe Met Thr Ala Thr Pro Pro Gly Thr Ser Asp
1805 1810 1815
Pro Phe Pro Glu Ser Asn Ser Pro Ile Ser Asp Leu Gln Thr Glu
1820 1825 1830
Ile Pro Asp Arg Ala Trp Asn Ser Gly Tyr Glu Trp Ile Thr Glu
1835 1840 1845
Tyr Thr Gly Lys Thr Val Trp Phe Val Pro Ser Val Lys Met Gly
1850 1855 1860
Asn Glu Ile Ala Leu Cys Leu Gln Arg Ala Gly Lys Lys Val Val
1865 1870 1875
Gln Leu Asn Arg Lys Ser Tyr Glu Thr Glu Tyr Pro Lys Cys Lys
1880 1885 1890
Asn Asp Asp Trp Asp Phe Val Ile Thr Thr Asp Ile Ser Glu Met
1895 1900 1905
Gly Ala Asn Phe Lys Ala Ser Arg Val Ile Asp Ser Arg Lys Ser
1910 1915 1920
Val Lys Pro Thr Ile Ile Thr Glu Gly Glu Gly Arg Val Ile Leu
1925 1930 1935
Gly Glu Pro Ser Ala Val Thr Ala Ala Ser Ala Ala Gln Arg Arg
1940 1945 1950
Gly Arg Ile Gly Arg Asn Pro Ser Gln Val Gly Asp Glu Tyr Cys
1955 1960 1965
Tyr Gly Gly His Thr Asn Glu Asp Asp Ser Asn Phe Ala His Trp
1970 1975 1980
Thr Glu Ala Arg Ile Met Leu Asp Asn Ile Asn Met Pro Asn Gly
1985 1990 1995
Leu Ile Ala Gln Phe Tyr Gln Pro Glu Arg Glu Lys Val Tyr Thr
2000 2005 2010
Met Asp Gly Glu Tyr Arg Leu Arg Gly Glu Glu Arg Lys Asn Phe
2015 2020 2025
Leu Glu Leu Leu Arg Thr Ala Asp Leu Pro Val Trp Leu Ala Tyr
2030 2035 2040
Lys Val Ala Ala Ala Gly Val Ser Tyr His Asp Arg Arg Trp Cys
2045 2050 2055
Phe Asp Gly Pro Arg Thr Asn Thr Ile Leu Glu Asp Asn Asn Glu
2060 2065 2070
Val Glu Val Ile Thr Lys Leu Gly Glu Arg Lys Ile Leu Arg Pro
2075 2080 2085
Arg Trp Ile Asp Ala Arg Val Tyr Ser Asp His Gln Ala Leu Lys
2090 2095 2100
Ala Phe Lys Asp Phe Ala Ser Gly Lys Arg Ser Gln Ile Gly Leu
2105 2110 2115
Ile Glu Val Leu Gly Lys Met Pro Glu His Phe Met Gly Lys Thr
2120 2125 2130
Trp Glu Ala Leu Asp Thr Met Tyr Val Val Ala Thr Ala Glu Lys
2135 2140 2145
Gly Gly Arg Ala His Arg Met Ala Leu Glu Glu Leu Pro Asp Ala
2150 2155 2160
Leu Gln Thr Ile Ala Leu Ile Ala Leu Leu Ser Val Met Thr Met
2165 2170 2175
Gly Val Phe Phe Leu Leu Met Gln Arg Lys Gly Ile Gly Lys Ile
2180 2185 2190
Gly Leu Gly Gly Ala Val Leu Gly Val Ala Thr Phe Phe Cys Trp
2195 2200 2205
Met Ala Glu Val Pro Gly Thr Lys Ile Ala Gly Met Leu Leu Leu
2210 2215 2220
Ser Leu Leu Leu Met Ile Val Leu Ile Pro Glu Pro Glu Lys Gln
2225 2230 2235
Arg Ser Gln Thr Asp Asn Gln Leu Ala Val Phe Leu Ile Cys Val
2240 2245 2250
Met Thr Leu Val Ser Ala Val Ala Ala Asn Glu Met Gly Trp Leu
2255 2260 2265
Asp Lys Thr Lys Ser Asp Ile Ser Ser Leu Phe Gly Gln Arg Ile
2270 2275 2280
Glu Val Lys Glu Asn Phe Ser Met Gly Glu Phe Leu Leu Asp Leu
2285 2290 2295
Arg Pro Ala Thr Ala Trp Ser Leu Tyr Ala Val Thr Thr Ala Val
2300 2305 2310
Leu Thr Pro Leu Leu Lys His Leu Ile Thr Ser Asp Tyr Ile Asn
2315 2320 2325
Thr Ser Leu Thr Ser Ile Asn Val Gln Ala Ser Ala Leu Phe Thr
2330 2335 2340
Leu Ala Arg Gly Phe Pro Phe Val Asp Val Gly Val Ser Ala Leu
2345 2350 2355
Leu Leu Ala Ala Gly Cys Trp Gly Gln Val Thr Leu Thr Val Thr
2360 2365 2370
Val Thr Ala Ala Thr Leu Leu Phe Cys His Tyr Ala Tyr Met Val
2375 2380 2385
Pro Gly Trp Gln Ala Glu Ala Met Arg Ser Ala Gln Arg Arg Thr
2390 2395 2400
Ala Ala Gly Ile Met Lys Asn Ala Val Val Asp Gly Ile Val Ala
2405 2410 2415
Thr Asp Val Pro Glu Leu Glu Arg Thr Thr Pro Ile Met Gln Lys
2420 2425 2430
Lys Val Gly Gln Ile Met Leu Ile Leu Val Ser Leu Ala Ala Val
2435 2440 2445
Val Val Asn Pro Ser Val Lys Thr Val Arg Glu Ala Gly Ile Leu
2450 2455 2460
Ile Thr Ala Ala Ala Val Thr Leu Trp Glu Asn Gly Ala Ser Ser
2465 2470 2475
Val Trp Asn Ala Thr Thr Ala Ile Gly Leu Cys His Ile Met Arg
2480 2485 2490
Gly Gly Trp Leu Ser Cys Leu Ser Ile Thr Trp Thr Leu Ile Lys
2495 2500 2505
Asn Met Glu Lys Pro Gly Leu Lys Arg Gly Gly Ala Lys Gly Arg
2510 2515 2520
Thr Leu Gly Glu Val Trp Lys Glu Arg Leu Asn Gln Met Thr Lys
2525 2530 2535
Glu Glu Phe Thr Arg Tyr Arg Lys Glu Ala Ile Ile Glu Val Asp
2540 2545 2550
Arg Ser Ala Ala Lys His Ala Arg Lys Glu Gly Asn Val Thr Gly
2555 2560 2565
Gly His Pro Val Ser Arg Gly Thr Ala Lys Leu Arg Trp Leu Val
2570 2575 2580
Glu Arg Arg Phe Leu Glu Pro Val Gly Lys Val Ile Asp Leu Gly
2585 2590 2595
Cys Gly Arg Gly Gly Trp Cys Tyr Tyr Met Ala Thr Gln Lys Arg
2600 2605 2610
Val Gln Glu Val Arg Gly Tyr Thr Lys Gly Gly Pro Gly His Glu
2615 2620 2625
Glu Pro Gln Leu Val Gln Ser Tyr Gly Trp Asn Ile Val Thr Met
2630 2635 2640
Lys Ser Gly Val Asp Val Phe Tyr Arg Pro Ser Glu Cys Cys Asp
2645 2650 2655
Thr Leu Leu Cys Asp Ile Gly Glu Ser Ser Ser Ser Ala Glu Val
2660 2665 2670
Glu Glu His Arg Thr Ile Arg Val Leu Glu Met Val Glu Asp Trp
2675 2680 2685
Leu His Arg Gly Pro Arg Glu Phe Cys Val Lys Val Leu Cys Pro
2690 2695 2700
Tyr Met Pro Lys Val Ile Glu Lys Met Glu Leu Leu Gln Arg Arg
2705 2710 2715
Tyr Gly Gly Gly Leu Val Arg Asn Pro Leu Ser Arg Asn Ser Thr
2720 2725 2730
His Glu Met Tyr Trp Val Ser Arg Ala Ser Gly Asn Val Val His
2735 2740 2745
Ser Val Asn Met Thr Ser Gln Val Leu Leu Gly Arg Met Glu Lys
2750 2755 2760
Arg Thr Trp Lys Gly Pro Gln Tyr Glu Glu Asp Val Asn Leu Gly
2765 2770 2775
Ser Gly Thr Arg Ala Val Gly Lys Pro Leu Leu Asn Ser Asp Thr
2780 2785 2790
Ser Lys Ile Lys Asn Arg Ile Glu Arg Leu Arg Arg Glu Tyr Ser
2795 2800 2805
Ser Thr Trp His His Asp Glu Asn His Pro Tyr Arg Thr Trp Asn
2810 2815 2820
Tyr His Gly Ser Tyr Asp Val Lys Pro Thr Gly Ser Ala Ser Ser
2825 2830 2835
Leu Val Asn Gly Val Val Arg Leu Leu Ser Lys Pro Trp Asp Thr
2840 2845 2850
Ile Thr Asn Val Thr Thr Met Ala Met Thr Asp Thr Thr Pro Phe
2855 2860 2865
Gly Gln Gln Arg Val Phe Lys Glu Lys Val Asp Thr Lys Ala Pro
2870 2875 2880
Glu Pro Pro Glu Gly Val Lys Tyr Val Leu Asn Glu Thr Thr Asn
2885 2890 2895
Trp Leu Trp Ala Phe Leu Ala Arg Glu Lys Arg Pro Arg Met Cys
2900 2905 2910
Ser Arg Glu Glu Phe Ile Arg Lys Val Asn Ser Asn Ala Ala Leu
2915 2920 2925
Gly Ala Met Phe Glu Glu Gln Asn Gln Trp Arg Ser Ala Arg Glu
2930 2935 2940
Ala Val Glu Asp Pro Lys Phe Trp Glu Met Val Asp Glu Glu Arg
2945 2950 2955
Glu Ala His Leu Arg Gly Glu Cys His Thr Cys Ile Tyr Asn Met
2960 2965 2970
Met Gly Lys Arg Glu Lys Lys Pro Gly Glu Phe Gly Lys Ala Lys
2975 2980 2985
Gly Ser Arg Ala Ile Trp Phe Met Trp Leu Gly Ala Arg Phe Leu
2990 2995 3000
Glu Phe Glu Ala Leu Gly Phe Leu Asn Glu Asp His Trp Leu Gly
3005 3010 3015
Arg Lys Asn Ser Gly Gly Gly Val Glu Gly Leu Gly Leu Gln Lys
3020 3025 3030
Leu Gly Tyr Ile Leu Arg Glu Val Gly Thr Arg Pro Gly Gly Lys
3035 3040 3045
Ile Tyr Ala Asp Asp Thr Ala Gly Trp Asp Thr Arg Ile Thr Arg
3050 3055 3060
Ala Asp Leu Glu Asn Glu Ala Lys Val Leu Glu Leu Leu Asp Gly
3065 3070 3075
Glu His Arg Arg Leu Ala Arg Ala Ile Ile Glu Leu Thr Tyr Arg
3080 3085 3090
His Lys Val Val Lys Val Met Arg Pro Ala Ala Asp Gly Arg Thr
3095 3100 3105
Val Met Asp Val Ile Ser Arg Glu Asp Gln Arg Gly Ser Gly Gln
3110 3115 3120
Val Val Thr Tyr Ala Leu Asn Thr Phe Thr Asn Leu Ala Val Gln
3125 3130 3135
Leu Val Arg Met Met Glu Gly Glu Gly Val Ile Gly Pro Asp Asp
3140 3145 3150
Val Glu Lys Leu Thr Lys Gly Lys Gly Pro Lys Val Arg Thr Trp
3155 3160 3165
Leu Phe Glu Asn Gly Glu Glu Arg Leu Ser Arg Met Ala Val Ser
3170 3175 3180
Gly Asp Asp Cys Val Val Lys Pro Leu Asp Asp Arg Phe Ala Thr
3185 3190 3195
Ser Leu His Phe Leu Asn Ala Met Ser Lys Val Arg Lys Asp Ile
3200 3205 3210
Gln Glu Trp Lys Pro Ser Thr Gly Trp Tyr Asp Trp Gln Gln Val
3215 3220 3225
Pro Phe Cys Ser Asn His Phe Thr Glu Leu Ile Met Lys Asp Gly
3230 3235 3240
Arg Thr Leu Val Val Pro Cys Arg Gly Gln Asp Glu Leu Val Gly
3245 3250 3255
Arg Ala Arg Ile Ser Pro Gly Ala Gly Trp Asn Val Arg Asp Thr
3260 3265 3270
Ala Cys Leu Ala Lys Ser Tyr Ala Gln Met Trp Leu Leu Leu Tyr
3275 3280 3285
Phe His Arg Arg Asp Leu Arg Leu Met Ala Asn Ala Ile Cys Ser
3290 3295 3300
Ala Val Pro Val Asn Trp Val Pro Thr Gly Arg Thr Thr Trp Ser
3305 3310 3315
Ile His Ala Gly Gly Glu Trp Met Thr Thr Glu Asp Met Leu Glu
3320 3325 3330
Val Trp Asn Arg Val Trp Ile Glu Glu Asn Glu Trp Met Glu Asp
3335 3340 3345
Lys Thr Pro Val Glu Lys Trp Ser Asp Val Pro Tyr Ser Gly Lys
3350 3355 3360
Arg Glu Asp Ile Trp Cys Gly Ser Leu Ile Gly Thr Arg Ala Arg
3365 3370 3375
Ala Thr Trp Ala Glu Asn Ile Gln Val Ala Ile Asn Gln Val Arg
3380 3385 3390
Ala Ile Ile Gly Asp Glu Lys Tyr Val Asp Tyr Met Ser Ser Leu
3395 3400 3405
Lys Arg Tyr Glu Asp Thr Thr Leu Val Glu Asp Thr Val Leu
3410 3415 3420
<210> 13
<211> 10996
<212> DNA
<213> 人工序列
<220>
<223> 具有E203 Asn 到 Asp 突变的西尼罗/登革 2 病毒嵌合体
<220>
<221> CDS
<222> (97)..(10365)
<400> 13
agtagttcgc ctgtgtgagc tgacaaactt agtagtgttt gtgaggatta acaacaatta 60
acacagtgcg agctgtttct tagcacgaag atctcg atg tct aag aaa cca gga 114
Met Ser Lys Lys Pro Gly
1 5
ggg ccc ggc aag agc cgg gct gtc aat atg cta aaa cgc gga atg ccc 162
Gly Pro Gly Lys Ser Arg Ala Val Asn Met Leu Lys Arg Gly Met Pro
10 15 20
cgc gtg ttg tcc ttg att gga ctg aag agg gct atg ttg agc ctg atc 210
Arg Val Leu Ser Leu Ile Gly Leu Lys Arg Ala Met Leu Ser Leu Ile
25 30 35
gac ggc aag ggg cca ata cga ttt gtg ttg gct ctc ttg gcg ttc ttc 258
Asp Gly Lys Gly Pro Ile Arg Phe Val Leu Ala Leu Leu Ala Phe Phe
40 45 50
agg ttc aca gca att gct ccg acc cga gca gtg ctg gat cga tgg aga 306
Arg Phe Thr Ala Ile Ala Pro Thr Arg Ala Val Leu Asp Arg Trp Arg
55 60 65 70
ggt gtg aac aaa caa aca gcg atg aaa cac ctt ctg agt ttt aag aag 354
Gly Val Asn Lys Gln Thr Ala Met Lys His Leu Leu Ser Phe Lys Lys
75 80 85
gaa cta ggg acc ttg acc agt gct atc aat cgg cgg agc tca aaa caa 402
Glu Leu Gly Thr Leu Thr Ser Ala Ile Asn Arg Arg Ser Ser Lys Gln
90 95 100
aag aaa aga tcc gcg ggc atg atc att atg ctg att cca aca gtg atg 450
Lys Lys Arg Ser Ala Gly Met Ile Ile Met Leu Ile Pro Thr Val Met
105 110 115
gcg ttc cat tta acc aca cgt aac gga gaa cca cac atg atc gtc agc 498
Ala Phe His Leu Thr Thr Arg Asn Gly Glu Pro His Met Ile Val Ser
120 125 130
aga caa gag aaa ggg aaa agt ctt ctg ttt aaa aca gag gat ggc gtg 546
Arg Gln Glu Lys Gly Lys Ser Leu Leu Phe Lys Thr Glu Asp Gly Val
135 140 145 150
aac atg tgt acc ctc atg gcc atg gac ctt ggt gaa ttg tgt gaa gac 594
Asn Met Cys Thr Leu Met Ala Met Asp Leu Gly Glu Leu Cys Glu Asp
155 160 165
aca atc acg tac aag tgt ccc ctt ctc agg cag aat gag cca gaa gac 642
Thr Ile Thr Tyr Lys Cys Pro Leu Leu Arg Gln Asn Glu Pro Glu Asp
170 175 180
ata gac tgt tgg tgc aac tct acg tcc acg tgg gta act tat ggg acg 690
Ile Asp Cys Trp Cys Asn Ser Thr Ser Thr Trp Val Thr Tyr Gly Thr
185 190 195
tgt acc acc atg gga gaa cat aga aga gaa aaa aga tca gtg gca ctc 738
Cys Thr Thr Met Gly Glu His Arg Arg Glu Lys Arg Ser Val Ala Leu
200 205 210
gtt cca cat gtg gga atg gga ctg gag aca cga act gaa aca tgg atg 786
Val Pro His Val Gly Met Gly Leu Glu Thr Arg Thr Glu Thr Trp Met
215 220 225 230
tca tca gaa ggg gcc tgg aaa cat gtc cag aga att gaa act tgg atc 834
Ser Ser Glu Gly Ala Trp Lys His Val Gln Arg Ile Glu Thr Trp Ile
235 240 245
ttg aga cat cca ggc ttc acc atg atg gca gca atc ctg gca tac acc 882
Leu Arg His Pro Gly Phe Thr Met Met Ala Ala Ile Leu Ala Tyr Thr
250 255 260
ata gga acg aca cat ttc caa aga gcc ctg att ttc atc tta ctg aca 930
Ile Gly Thr Thr His Phe Gln Arg Ala Leu Ile Phe Ile Leu Leu Thr
265 270 275
gct gtc act cct tca atg aca atg cgt tgc ata gga atg tca aat aga 978
Ala Val Thr Pro Ser Met Thr Met Arg Cys Ile Gly Met Ser Asn Arg
280 285 290
gac ttt gtg gaa ggg gtt tca gga gga agc tgg gtt gac ata gtc tta 1026
Asp Phe Val Glu Gly Val Ser Gly Gly Ser Trp Val Asp Ile Val Leu
295 300 305 310
gaa cat gga agc tgt gtg acg acg atg gca aaa aac aaa cca aca ttg 1074
Glu His Gly Ser Cys Val Thr Thr Met Ala Lys Asn Lys Pro Thr Leu
315 320 325
gat ttt gaa ctg ata aaa aca gaa gcc aaa cag cct gcc acc cta agg 1122
Asp Phe Glu Leu Ile Lys Thr Glu Ala Lys Gln Pro Ala Thr Leu Arg
330 335 340
aag tac tgt ata gag gca aag cta acc aac aca aca aca gaa tct cgc 1170
Lys Tyr Cys Ile Glu Ala Lys Leu Thr Asn Thr Thr Thr Glu Ser Arg
345 350 355
tgc cca aca caa ggg gaa ccc agc cta aat gaa gag cag gac aaa agg 1218
Cys Pro Thr Gln Gly Glu Pro Ser Leu Asn Glu Glu Gln Asp Lys Arg
360 365 370
ttc gtc tgc aaa cac tcc atg gta gac aga gga tgg gga aat gga tgt 1266
Phe Val Cys Lys His Ser Met Val Asp Arg Gly Trp Gly Asn Gly Cys
375 380 385 390
gga cta ttt gga aag gga ggc att gtg acc tgt gct atg ttc aga tgc 1314
Gly Leu Phe Gly Lys Gly Gly Ile Val Thr Cys Ala Met Phe Arg Cys
395 400 405
aaa aag aac atg gaa gga aaa gtt gtg caa cca gaa aac ttg gaa tac 1362
Lys Lys Asn Met Glu Gly Lys Val Val Gln Pro Glu Asn Leu Glu Tyr
410 415 420
acc att gtg ata aca cct cac tca ggg gaa gag cat gca gtc gga aat 1410
Thr Ile Val Ile Thr Pro His Ser Gly Glu Glu His Ala Val Gly Asn
425 430 435
gac aca gga aaa cat ggc aag gaa atc aaa ata aca cca cag agt tcc 1458
Asp Thr Gly Lys His Gly Lys Glu Ile Lys Ile Thr Pro Gln Ser Ser
440 445 450
atc aca gaa gca gaa ttg aca ggt tat ggc act gtc aca atg gag tgc 1506
Ile Thr Glu Ala Glu Leu Thr Gly Tyr Gly Thr Val Thr Met Glu Cys
455 460 465 470
tct cca aga acg ggc ctc gac ttc aat gag atg gtg ttg ttg cag atg 1554
Ser Pro Arg Thr Gly Leu Asp Phe Asn Glu Met Val Leu Leu Gln Met
475 480 485
gaa gat aaa gct tgg ctg gtg cac agg caa tgg ttc cta gac ctg ccg 1602
Glu Asp Lys Ala Trp Leu Val His Arg Gln Trp Phe Leu Asp Leu Pro
490 495 500
tta cca tgg ttg ccc gga gcg gac aca caa ggg tca aat tgg ata cag 1650
Leu Pro Trp Leu Pro Gly Ala Asp Thr Gln Gly Ser Asn Trp Ile Gln
505 510 515
aaa gag aca ttg gtc act ttc aaa aat ccc cat gcg aag aaa cag gat 1698
Lys Glu Thr Leu Val Thr Phe Lys Asn Pro His Ala Lys Lys Gln Asp
520 525 530
gtt gtt gtt tta gga tcc caa gaa ggg gcc atg cac aca gca ctt aca 1746
Val Val Val Leu Gly Ser Gln Glu Gly Ala Met His Thr Ala Leu Thr
535 540 545 550
ggg gcc aca gaa atc caa atg tca tca gga aac tta ctc ttc aca gga 1794
Gly Ala Thr Glu Ile Gln Met Ser Ser Gly Asn Leu Leu Phe Thr Gly
555 560 565
cat ctc aag tgc agg ctg aga atg gac aag cta cag ctc aaa gga atg 1842
His Leu Lys Cys Arg Leu Arg Met Asp Lys Leu Gln Leu Lys Gly Met
570 575 580
tca tac tct atg tgc aca gga aag ttt aaa gtt gtg aag gaa ata gca 1890
Ser Tyr Ser Met Cys Thr Gly Lys Phe Lys Val Val Lys Glu Ile Ala
585 590 595
gaa aca caa cat gga aca ata gtt atc aga gtg caa tat gaa ggg gac 1938
Glu Thr Gln His Gly Thr Ile Val Ile Arg Val Gln Tyr Glu Gly Asp
600 605 610
ggc tct cca tgc aag atc cct ttt gag ata atg gat ttg gaa aaa aga 1986
Gly Ser Pro Cys Lys Ile Pro Phe Glu Ile Met Asp Leu Glu Lys Arg
615 620 625 630
cat gtc tta ggt cgc ctg att aca gtc aac cca att gtg aca gaa aaa 2034
His Val Leu Gly Arg Leu Ile Thr Val Asn Pro Ile Val Thr Glu Lys
635 640 645
gat agc cca gtc aac ata gaa gca gaa cct cca ttc gga gac agc tac 2082
Asp Ser Pro Val Asn Ile Glu Ala Glu Pro Pro Phe Gly Asp Ser Tyr
650 655 660
atc atc ata gga gta gag ccg gga caa ctg aag ctc aac tgg ttt aag 2130
Ile Ile Ile Gly Val Glu Pro Gly Gln Leu Lys Leu Asn Trp Phe Lys
665 670 675
aaa gga agt tct atc ggc caa atg ttt gag aca aca atg agg ggg gcg 2178
Lys Gly Ser Ser Ile Gly Gln Met Phe Glu Thr Thr Met Arg Gly Ala
680 685 690
aag aga atg gcc att tta ggt gac aca gcc tgg gat ttt gga tcc ttg 2226
Lys Arg Met Ala Ile Leu Gly Asp Thr Ala Trp Asp Phe Gly Ser Leu
695 700 705 710
gga gga gtg ttt aca tct ata gga aag gct ctc cac caa gtc ttt gga 2274
Gly Gly Val Phe Thr Ser Ile Gly Lys Ala Leu His Gln Val Phe Gly
715 720 725
gca atc tat gga gct gcc ttc agt ggg gtt tca tgg act atg aaa atc 2322
Ala Ile Tyr Gly Ala Ala Phe Ser Gly Val Ser Trp Thr Met Lys Ile
730 735 740
ctc ata gga gtc att atc aca tgg ata gga atg aat tca cgc agc acc 2370
Leu Ile Gly Val Ile Ile Thr Trp Ile Gly Met Asn Ser Arg Ser Thr
745 750 755
tca ctg tct gtg aca cta gta ttg gtg gga att gtg aca ctg tat ttg 2418
Ser Leu Ser Val Thr Leu Val Leu Val Gly Ile Val Thr Leu Tyr Leu
760 765 770
gga gtc atg gtg cag gcc gat tcc gga tgt gcc ata gac atc agc cgg 2466
Gly Val Met Val Gln Ala Asp Ser Gly Cys Ala Ile Asp Ile Ser Arg
775 780 785 790
caa gag ctg aga tgt gga agt gga gtg ttc ata cac aat gat gtg gag 2514
Gln Glu Leu Arg Cys Gly Ser Gly Val Phe Ile His Asn Asp Val Glu
795 800 805
gct tgg atg gac cgg tac aag tat tac cct gaa acg cca caa ggc cta 2562
Ala Trp Met Asp Arg Tyr Lys Tyr Tyr Pro Glu Thr Pro Gln Gly Leu
810 815 820
gcc aag atc att cag aaa gct cat aag gaa gga gtg tgc ggt cta cga 2610
Ala Lys Ile Ile Gln Lys Ala His Lys Glu Gly Val Cys Gly Leu Arg
825 830 835
tca gtt tcc aga ctg gag cat caa atg tgg gaa gca gtg aag gac gag 2658
Ser Val Ser Arg Leu Glu His Gln Met Trp Glu Ala Val Lys Asp Glu
840 845 850
ctg aac act ctt ttg aag gag aat ggt gtg gac ctt agt gtc gtg gtt 2706
Leu Asn Thr Leu Leu Lys Glu Asn Gly Val Asp Leu Ser Val Val Val
855 860 865 870
gag aaa cag gag gga atg tac aag tca gca cct aaa cgc ctc acc gcc 2754
Glu Lys Gln Glu Gly Met Tyr Lys Ser Ala Pro Lys Arg Leu Thr Ala
875 880 885
acc acg gaa aaa ttg gaa att ggc tgg aag gcc tgg gga aag agt att 2802
Thr Thr Glu Lys Leu Glu Ile Gly Trp Lys Ala Trp Gly Lys Ser Ile
890 895 900
tta ttt gca cca gaa ctc gcc aac aac acc ttt gtg gtt gat ggt ccg 2850
Leu Phe Ala Pro Glu Leu Ala Asn Asn Thr Phe Val Val Asp Gly Pro
905 910 915
gag acc aag gaa tgt ccg act cag aat cgc gct tgg aat agc tta gaa 2898
Glu Thr Lys Glu Cys Pro Thr Gln Asn Arg Ala Trp Asn Ser Leu Glu
920 925 930
gtg gag gat ttt gga ttt ggt ctc acc agc act cgg atg ttc ctg aag 2946
Val Glu Asp Phe Gly Phe Gly Leu Thr Ser Thr Arg Met Phe Leu Lys
935 940 945 950
gtc aga gag agc aac aca act gaa tgt gac tcg aag atc att gga acg 2994
Val Arg Glu Ser Asn Thr Thr Glu Cys Asp Ser Lys Ile Ile Gly Thr
955 960 965
gct gtc aag aac aac ttg gcg atc cac agt gac ctg tcc tat tgg att 3042
Ala Val Lys Asn Asn Leu Ala Ile His Ser Asp Leu Ser Tyr Trp Ile
970 975 980
gaa agc agg ctc aat gat acg tgg aag ctt gaa agg gca gtt ctg ggt 3090
Glu Ser Arg Leu Asn Asp Thr Trp Lys Leu Glu Arg Ala Val Leu Gly
985 990 995
gaa gtc aaa tca tgt acg tgg cct gag acg cat acc ttg tgg ggc 3135
Glu Val Lys Ser Cys Thr Trp Pro Glu Thr His Thr Leu Trp Gly
1000 1005 1010
gat gga atc ctt gag agt gac ttg ata ata cca gtc aca ctg gcg 3180
Asp Gly Ile Leu Glu Ser Asp Leu Ile Ile Pro Val Thr Leu Ala
1015 1020 1025
gga cca cga agc aat cac aat cgg aga cct ggg tac aag aca caa 3225
Gly Pro Arg Ser Asn His Asn Arg Arg Pro Gly Tyr Lys Thr Gln
1030 1035 1040
aac cag ggc cca tgg gac gaa ggc cgg gta gag att gac ttc gat 3270
Asn Gln Gly Pro Trp Asp Glu Gly Arg Val Glu Ile Asp Phe Asp
1045 1050 1055
tac tgc cca gga act acg gtc acc ctg agt gag agc tgc gga cac 3315
Tyr Cys Pro Gly Thr Thr Val Thr Leu Ser Glu Ser Cys Gly His
1060 1065 1070
cgt gga cct gcc act cgc acc acc aca gag agc gga aag ttg ata 3360
Arg Gly Pro Ala Thr Arg Thr Thr Thr Glu Ser Gly Lys Leu Ile
1075 1080 1085
aca gat tgg tgc tgc agg agc tgc acc tta cca cca ctg cgc tac 3405
Thr Asp Trp Cys Cys Arg Ser Cys Thr Leu Pro Pro Leu Arg Tyr
1090 1095 1100
caa act gac agc ggc tgt tgg tat ggt atg gag atc aga cca cag 3450
Gln Thr Asp Ser Gly Cys Trp Tyr Gly Met Glu Ile Arg Pro Gln
1105 1110 1115
aga cat gat gaa aag acc ctc gtg cag tca caa gtg aat gct tat 3495
Arg His Asp Glu Lys Thr Leu Val Gln Ser Gln Val Asn Ala Tyr
1120 1125 1130
aat gct gat atg att gac cct ttt cag ttg ggc ctt ctg gtc gtg 3540
Asn Ala Asp Met Ile Asp Pro Phe Gln Leu Gly Leu Leu Val Val
1135 1140 1145
ttc ttg gcc acc cag gag gtc ctt cgc aag agg tgg aca gcc aag 3585
Phe Leu Ala Thr Gln Glu Val Leu Arg Lys Arg Trp Thr Ala Lys
1150 1155 1160
atc agc atg cca gct ata ctg att gct ctg cta gtc ctg gtg ttt 3630
Ile Ser Met Pro Ala Ile Leu Ile Ala Leu Leu Val Leu Val Phe
1165 1170 1175
ggg ggc att act tac act gat gtg tta cgc tat gtc atc ttg gtg 3675
Gly Gly Ile Thr Tyr Thr Asp Val Leu Arg Tyr Val Ile Leu Val
1180 1185 1190
ggg gca gct ttc gca gaa tct aat tcg gga gga gac gtg gta cac 3720
Gly Ala Ala Phe Ala Glu Ser Asn Ser Gly Gly Asp Val Val His
1195 1200 1205
ttg gcg ctc atg gcg acc ttc aag ata caa cca gtg ttt atg gtg 3765
Leu Ala Leu Met Ala Thr Phe Lys Ile Gln Pro Val Phe Met Val
1210 1215 1220
gca tcg ttt ctc aaa gcg aga tgg acc aac cag gag aac att ttg 3810
Ala Ser Phe Leu Lys Ala Arg Trp Thr Asn Gln Glu Asn Ile Leu
1225 1230 1235
ttg atg ttg gcg gct gtt ttc ttt caa atg gct tat tac gat gcc 3855
Leu Met Leu Ala Ala Val Phe Phe Gln Met Ala Tyr Tyr Asp Ala
1240 1245 1250
cgc caa att ctg ctc tgg gag atc cct gat gtg ttg aat tca ctg 3900
Arg Gln Ile Leu Leu Trp Glu Ile Pro Asp Val Leu Asn Ser Leu
1255 1260 1265
gcg gta gct tgg atg ata ctg aga gcc ata aca ttc aca acg aca 3945
Ala Val Ala Trp Met Ile Leu Arg Ala Ile Thr Phe Thr Thr Thr
1270 1275 1280
tca aac gtg gtt gtt ccg ctg cta gcc ctg cta aca ccc ggg ctg 3990
Ser Asn Val Val Val Pro Leu Leu Ala Leu Leu Thr Pro Gly Leu
1285 1290 1295
aga tgc ttg aat ctg gat gtg tac agg ata ctg ctg ttg atg gtc 4035
Arg Cys Leu Asn Leu Asp Val Tyr Arg Ile Leu Leu Leu Met Val
1300 1305 1310
gga ata ggc agc ttg atc agg gag aag agg agt gca gct gca aaa 4080
Gly Ile Gly Ser Leu Ile Arg Glu Lys Arg Ser Ala Ala Ala Lys
1315 1320 1325
aag aaa gga gca agt ctg cta tgc ttg gct cta gcc tca aca gga 4125
Lys Lys Gly Ala Ser Leu Leu Cys Leu Ala Leu Ala Ser Thr Gly
1330 1335 1340
ctt ttc aac ccc atg atc ctt gct gct gga ctg att gca tgt gat 4170
Leu Phe Asn Pro Met Ile Leu Ala Ala Gly Leu Ile Ala Cys Asp
1345 1350 1355
ccc aac cgt aaa cgc gga tgg ccc gca act gaa gtg atg aca gct 4215
Pro Asn Arg Lys Arg Gly Trp Pro Ala Thr Glu Val Met Thr Ala
1360 1365 1370
gtc ggc cta atg ttt gcc atc gtc gga ggg ctg gca gag ctt gac 4260
Val Gly Leu Met Phe Ala Ile Val Gly Gly Leu Ala Glu Leu Asp
1375 1380 1385
att gac tcc atg gcc att cca atg act atc gcg ggg ctc atg ttt 4305
Ile Asp Ser Met Ala Ile Pro Met Thr Ile Ala Gly Leu Met Phe
1390 1395 1400
gct gct ttc gtg att tct ggg aaa tca aca gat atg tgg att gag 4350
Ala Ala Phe Val Ile Ser Gly Lys Ser Thr Asp Met Trp Ile Glu
1405 1410 1415
aga acg gcg gac att tcc tgg gaa agt gat gca gaa att aca ggc 4395
Arg Thr Ala Asp Ile Ser Trp Glu Ser Asp Ala Glu Ile Thr Gly
1420 1425 1430
tcg agc gaa aga gtt gat gtg cgg ctt gat gat gat gga aac ttc 4440
Ser Ser Glu Arg Val Asp Val Arg Leu Asp Asp Asp Gly Asn Phe
1435 1440 1445
cag ctc atg aat gat cca gga gca cct tgg aag ata tgg atg ctc 4485
Gln Leu Met Asn Asp Pro Gly Ala Pro Trp Lys Ile Trp Met Leu
1450 1455 1460
aga atg gtc tgt ctc gcg att agt gcg tac acc ccc tgg gca atc 4530
Arg Met Val Cys Leu Ala Ile Ser Ala Tyr Thr Pro Trp Ala Ile
1465 1470 1475
ttg ccc tca gta gtt gga ttt tgg ata act ctc caa tac aca aag 4575
Leu Pro Ser Val Val Gly Phe Trp Ile Thr Leu Gln Tyr Thr Lys
1480 1485 1490
aga gga ggc gtg ttg tgg gac act ccc tca cca aag gag tac aaa 4620
Arg Gly Gly Val Leu Trp Asp Thr Pro Ser Pro Lys Glu Tyr Lys
1495 1500 1505
aag ggg gac acg acc acc ggc gtc tac agg atc atg act cgt ggg 4665
Lys Gly Asp Thr Thr Thr Gly Val Tyr Arg Ile Met Thr Arg Gly
1510 1515 1520
ctg ctc ggc agt tat caa gca gga gcg ggc gtg atg gtt gaa ggt 4710
Leu Leu Gly Ser Tyr Gln Ala Gly Ala Gly Val Met Val Glu Gly
1525 1530 1535
gtt ttc cac acc ctt tgg cat aca aca aaa gga gcc gct ttg atg 4755
Val Phe His Thr Leu Trp His Thr Thr Lys Gly Ala Ala Leu Met
1540 1545 1550
agc gga gag ggc cgc ctg gac cca tac tgg ggc agt gtc aag gag 4800
Ser Gly Glu Gly Arg Leu Asp Pro Tyr Trp Gly Ser Val Lys Glu
1555 1560 1565
gat cga ctt tgt tac gga gga ccc tgg aaa ttg cag cac aag tgg 4845
Asp Arg Leu Cys Tyr Gly Gly Pro Trp Lys Leu Gln His Lys Trp
1570 1575 1580
aac ggg cag gat gag gtg cag atg att gtg gtg gaa cct ggc agg 4890
Asn Gly Gln Asp Glu Val Gln Met Ile Val Val Glu Pro Gly Arg
1585 1590 1595
aac gtt aag aac gtc cag acg aaa cca ggg gtg ttc aaa aca cct 4935
Asn Val Lys Asn Val Gln Thr Lys Pro Gly Val Phe Lys Thr Pro
1600 1605 1610
gaa gga gaa atc ggg gcc gtg act ttg gac ttc ccc act gga aca 4980
Glu Gly Glu Ile Gly Ala Val Thr Leu Asp Phe Pro Thr Gly Thr
1615 1620 1625
tca ggc tca cca ata gtg gac aaa aac ggt gat gtg att ggg ctt 5025
Ser Gly Ser Pro Ile Val Asp Lys Asn Gly Asp Val Ile Gly Leu
1630 1635 1640
tat ggc aat gga gtc ata atg ccc aac ggc tca tac ata agc gcg 5070
Tyr Gly Asn Gly Val Ile Met Pro Asn Gly Ser Tyr Ile Ser Ala
1645 1650 1655
ata gtg cag ggt gaa agg atg gat gag cca atc cca gcc gga ttc 5115
Ile Val Gln Gly Glu Arg Met Asp Glu Pro Ile Pro Ala Gly Phe
1660 1665 1670
gaa cct gag atg ctg agg aaa aaa cag atc act gta ctg gat ctc 5160
Glu Pro Glu Met Leu Arg Lys Lys Gln Ile Thr Val Leu Asp Leu
1675 1680 1685
cat ccc ggc gcc ggt aaa aca agg agg att ctg cca cag atc atc 5205
His Pro Gly Ala Gly Lys Thr Arg Arg Ile Leu Pro Gln Ile Ile
1690 1695 1700
aaa gag gcc ata aac aga aga ctg aga aca gcc gtg cta gca cca 5250
Lys Glu Ala Ile Asn Arg Arg Leu Arg Thr Ala Val Leu Ala Pro
1705 1710 1715
acc agg gtt gtg gct gct gag atg gct gaa gca ctg aga gga ctg 5295
Thr Arg Val Val Ala Ala Glu Met Ala Glu Ala Leu Arg Gly Leu
1720 1725 1730
ccc atc cgg tac cag aca tcc gca gtg ccc aga gaa cat aat gga 5340
Pro Ile Arg Tyr Gln Thr Ser Ala Val Pro Arg Glu His Asn Gly
1735 1740 1745
aat gag att gtt gat gtc atg tgt cat gct acc ctc acc cac agg 5385
Asn Glu Ile Val Asp Val Met Cys His Ala Thr Leu Thr His Arg
1750 1755 1760
ctg atg tct cct cac agg gtg ccg aac tac aac ctg ttc gtg atg 5430
Leu Met Ser Pro His Arg Val Pro Asn Tyr Asn Leu Phe Val Met
1765 1770 1775
gat gag gct cat ttc acc gac cca gct agc att gca gca aga ggt 5475
Asp Glu Ala His Phe Thr Asp Pro Ala Ser Ile Ala Ala Arg Gly
1780 1785 1790
tac att tcc aca aag gtc gag cta ggg gag gcg gcg gca ata ttc 5520
Tyr Ile Ser Thr Lys Val Glu Leu Gly Glu Ala Ala Ala Ile Phe
1795 1800 1805
atg aca gcc acc cca cca ggc act tca gat cca ttc cca gag tcc 5565
Met Thr Ala Thr Pro Pro Gly Thr Ser Asp Pro Phe Pro Glu Ser
1810 1815 1820
aat tca cca att tcc gac tta cag act gag atc ccg gat cga gct 5610
Asn Ser Pro Ile Ser Asp Leu Gln Thr Glu Ile Pro Asp Arg Ala
1825 1830 1835
tgg aac tct gga tac gaa tgg atc aca gaa tac acc ggg aag acg 5655
Trp Asn Ser Gly Tyr Glu Trp Ile Thr Glu Tyr Thr Gly Lys Thr
1840 1845 1850
gtt tgg ttt gtg cct agt gtc aag atg ggg aat gag att gcc ctt 5700
Val Trp Phe Val Pro Ser Val Lys Met Gly Asn Glu Ile Ala Leu
1855 1860 1865
tgc cta caa cgt gct gga aag aaa gta gtc caa ttg aac aga aag 5745
Cys Leu Gln Arg Ala Gly Lys Lys Val Val Gln Leu Asn Arg Lys
1870 1875 1880
tcg tac gag acg gag tac cca aaa tgt aag aac gat gat tgg gac 5790
Ser Tyr Glu Thr Glu Tyr Pro Lys Cys Lys Asn Asp Asp Trp Asp
1885 1890 1895
ttt gtt atc aca aca gac ata tct gaa atg ggg gct aac ttc aag 5835
Phe Val Ile Thr Thr Asp Ile Ser Glu Met Gly Ala Asn Phe Lys
1900 1905 1910
gcg agc agg gtg att gac agc cgg aag agt gtg aaa cca acc atc 5880
Ala Ser Arg Val Ile Asp Ser Arg Lys Ser Val Lys Pro Thr Ile
1915 1920 1925
ata aca gaa gga gaa ggg aga gtg atc ctg gga gaa cca tct gca 5925
Ile Thr Glu Gly Glu Gly Arg Val Ile Leu Gly Glu Pro Ser Ala
1930 1935 1940
gtg aca gca gct agt gcc gcc cag aga cgt gga cgt atc ggt aga 5970
Val Thr Ala Ala Ser Ala Ala Gln Arg Arg Gly Arg Ile Gly Arg
1945 1950 1955
aat ccg tcg caa gtt ggt gat gag tac tgt tat ggg ggg cac acg 6015
Asn Pro Ser Gln Val Gly Asp Glu Tyr Cys Tyr Gly Gly His Thr
1960 1965 1970
aat gaa gac gac tcg aac ttc gcc cat tgg act gag gca cga atc 6060
Asn Glu Asp Asp Ser Asn Phe Ala His Trp Thr Glu Ala Arg Ile
1975 1980 1985
atg ctg gac aac atc aac atg cca aac gga ctg atc gct caa ttc 6105
Met Leu Asp Asn Ile Asn Met Pro Asn Gly Leu Ile Ala Gln Phe
1990 1995 2000
tac caa cca gag cgt gag aag gta tat acc atg gat ggg gaa tac 6150
Tyr Gln Pro Glu Arg Glu Lys Val Tyr Thr Met Asp Gly Glu Tyr
2005 2010 2015
cgg ctc aga gga gaa gag aga aaa aac ttt ctg gaa ctg ttg agg 6195
Arg Leu Arg Gly Glu Glu Arg Lys Asn Phe Leu Glu Leu Leu Arg
2020 2025 2030
act gca gat ctg cca gtt tgg ctg gct tac aag gtt gca gcg gct 6240
Thr Ala Asp Leu Pro Val Trp Leu Ala Tyr Lys Val Ala Ala Ala
2035 2040 2045
gga gtg tca tac cac gac cgg agg tgg tgc ttt gat ggt cct agg 6285
Gly Val Ser Tyr His Asp Arg Arg Trp Cys Phe Asp Gly Pro Arg
2050 2055 2060
aca aac aca att tta gaa gac aac aac gaa gtg gaa gtc atc acg 6330
Thr Asn Thr Ile Leu Glu Asp Asn Asn Glu Val Glu Val Ile Thr
2065 2070 2075
aag ctt ggt gaa agg aag att ctg agg ccg cgc tgg att gac gcc 6375
Lys Leu Gly Glu Arg Lys Ile Leu Arg Pro Arg Trp Ile Asp Ala
2080 2085 2090
agg gtg tac tcg gat cac cag gca cta aag gcg ttc aag gac ttc 6420
Arg Val Tyr Ser Asp His Gln Ala Leu Lys Ala Phe Lys Asp Phe
2095 2100 2105
gcc tcg gga aaa cgt tct cag ata ggg ctc att gag gtt ctg gga 6465
Ala Ser Gly Lys Arg Ser Gln Ile Gly Leu Ile Glu Val Leu Gly
2110 2115 2120
aag atg cct gag cac ttc atg ggg aag aca tgg gaa gca ctt gac 6510
Lys Met Pro Glu His Phe Met Gly Lys Thr Trp Glu Ala Leu Asp
2125 2130 2135
acc atg tac gtt gtg gcc act gca gag aaa gga gga aga gct cac 6555
Thr Met Tyr Val Val Ala Thr Ala Glu Lys Gly Gly Arg Ala His
2140 2145 2150
aga atg gcc ctg gag gaa ctg cca gat gct ctt cag aca att gcc 6600
Arg Met Ala Leu Glu Glu Leu Pro Asp Ala Leu Gln Thr Ile Ala
2155 2160 2165
ttg att gcc tta ttg agt gtg atg acc atg gga gta ttc ttc ctc 6645
Leu Ile Ala Leu Leu Ser Val Met Thr Met Gly Val Phe Phe Leu
2170 2175 2180
ctc atg cag cgg aag ggc att gga aag ata ggt ttg gga ggc gct 6690
Leu Met Gln Arg Lys Gly Ile Gly Lys Ile Gly Leu Gly Gly Ala
2185 2190 2195
gtc ttg gga gtc gcg acc ttt ttc tgt tgg atg gct gaa gtt cca 6735
Val Leu Gly Val Ala Thr Phe Phe Cys Trp Met Ala Glu Val Pro
2200 2205 2210
gga acg aag atc gcc gga atg ttg ctg ctc tcc ctt ctc ttg atg 6780
Gly Thr Lys Ile Ala Gly Met Leu Leu Leu Ser Leu Leu Leu Met
2215 2220 2225
att gtg cta att cct gag cca gag aag caa cgt tcg cag aca gac 6825
Ile Val Leu Ile Pro Glu Pro Glu Lys Gln Arg Ser Gln Thr Asp
2230 2235 2240
aac cag cta gcc gtg ttc ctg att tgt gtc atg acc ctt gtg agc 6870
Asn Gln Leu Ala Val Phe Leu Ile Cys Val Met Thr Leu Val Ser
2245 2250 2255
gca gtg gca gcc aac gag atg ggt tgg cta gat aag acc aag agt 6915
Ala Val Ala Ala Asn Glu Met Gly Trp Leu Asp Lys Thr Lys Ser
2260 2265 2270
gac ata agc agt ttg ttt ggg caa aga att gag gtc aag gag aat 6960
Asp Ile Ser Ser Leu Phe Gly Gln Arg Ile Glu Val Lys Glu Asn
2275 2280 2285
ttc agc atg gga gag ttt ctt ttg gac ttg agg cct gca aca gcc 7005
Phe Ser Met Gly Glu Phe Leu Leu Asp Leu Arg Pro Ala Thr Ala
2290 2295 2300
tgg tca ctg tac gct gtg aca aca gcg gtc ctc act cca ctg cta 7050
Trp Ser Leu Tyr Ala Val Thr Thr Ala Val Leu Thr Pro Leu Leu
2305 2310 2315
aag cat ttg atc acg tca gat tac atc aac acc tca ttg acc tca 7095
Lys His Leu Ile Thr Ser Asp Tyr Ile Asn Thr Ser Leu Thr Ser
2320 2325 2330
ata aac gtt cag gca agt gca cta ttc aca ctc gcg cga ggc ttc 7140
Ile Asn Val Gln Ala Ser Ala Leu Phe Thr Leu Ala Arg Gly Phe
2335 2340 2345
ccc ttc gtc gat gtt gga gtg tcg gct ctc ctg cta gca gcc gga 7185
Pro Phe Val Asp Val Gly Val Ser Ala Leu Leu Leu Ala Ala Gly
2350 2355 2360
tgc tgg gga caa gtc acc ctc acc gtt acg gta aca gcg gca aca 7230
Cys Trp Gly Gln Val Thr Leu Thr Val Thr Val Thr Ala Ala Thr
2365 2370 2375
ctc ctt ttt tgc cac tat gcc tac atg gtt ccc ggt tgg caa gct 7275
Leu Leu Phe Cys His Tyr Ala Tyr Met Val Pro Gly Trp Gln Ala
2380 2385 2390
gag gca atg cgc tca gcc cag cgg cgg aca gcg gcc gga atc atg 7320
Glu Ala Met Arg Ser Ala Gln Arg Arg Thr Ala Ala Gly Ile Met
2395 2400 2405
aag aac gct gta gtg gat ggc atc gtg gcc acg gac gtc cca gaa 7365
Lys Asn Ala Val Val Asp Gly Ile Val Ala Thr Asp Val Pro Glu
2410 2415 2420
tta gag cgc acc aca ccc atc atg cag aag aaa gtt gga cag atc 7410
Leu Glu Arg Thr Thr Pro Ile Met Gln Lys Lys Val Gly Gln Ile
2425 2430 2435
atg ctg atc ttg gtg tct cta gct gca gta gta gtg aac ccg tct 7455
Met Leu Ile Leu Val Ser Leu Ala Ala Val Val Val Asn Pro Ser
2440 2445 2450
gtg aag aca gta cga gaa gcc gga att ttg atc acg gcc gca gcg 7500
Val Lys Thr Val Arg Glu Ala Gly Ile Leu Ile Thr Ala Ala Ala
2455 2460 2465
gtg acg ctt tgg gag aat gga gca agc tct gtt tgg aac gca aca 7545
Val Thr Leu Trp Glu Asn Gly Ala Ser Ser Val Trp Asn Ala Thr
2470 2475 2480
act gcc atc gga ctc tgc cac atc atg cgt ggg ggt tgg ttg tca 7590
Thr Ala Ile Gly Leu Cys His Ile Met Arg Gly Gly Trp Leu Ser
2485 2490 2495
tgt cta tcc ata aca tgg aca ctc ata aag aac atg gaa aaa cca 7635
Cys Leu Ser Ile Thr Trp Thr Leu Ile Lys Asn Met Glu Lys Pro
2500 2505 2510
gga cta aaa aga ggt ggg gca aaa gga cgc acc ttg gga gag gtt 7680
Gly Leu Lys Arg Gly Gly Ala Lys Gly Arg Thr Leu Gly Glu Val
2515 2520 2525
tgg aaa gaa aga ctc aac cag atg aca aaa gaa gag ttc act agg 7725
Trp Lys Glu Arg Leu Asn Gln Met Thr Lys Glu Glu Phe Thr Arg
2530 2535 2540
tac cgc aaa gag gcc atc atc gaa gtc gat cgc tca gcg gca aaa 7770
Tyr Arg Lys Glu Ala Ile Ile Glu Val Asp Arg Ser Ala Ala Lys
2545 2550 2555
cac gcc agg aaa gaa ggc aat gtc act gga ggg cat cca gtc tct 7815
His Ala Arg Lys Glu Gly Asn Val Thr Gly Gly His Pro Val Ser
2560 2565 2570
agg ggc aca gca aaa ctg aga tgg ctg gtc gaa cgg agg ttt ctc 7860
Arg Gly Thr Ala Lys Leu Arg Trp Leu Val Glu Arg Arg Phe Leu
2575 2580 2585
gaa ccg gtc gga aaa gtg att gac ctt gga tgt gga aga ggc ggt 7905
Glu Pro Val Gly Lys Val Ile Asp Leu Gly Cys Gly Arg Gly Gly
2590 2595 2600
tgg tgt tac tat atg gca acc caa aaa aga gtc caa gaa gtc aga 7950
Trp Cys Tyr Tyr Met Ala Thr Gln Lys Arg Val Gln Glu Val Arg
2605 2610 2615
ggg tac aca aag ggc ggt ccc gga cat gaa gag ccc caa cta gtg 7995
Gly Tyr Thr Lys Gly Gly Pro Gly His Glu Glu Pro Gln Leu Val
2620 2625 2630
caa agt tat gga tgg aac att gtc acc atg aag agt gga gtg gat 8040
Gln Ser Tyr Gly Trp Asn Ile Val Thr Met Lys Ser Gly Val Asp
2635 2640 2645
gtg ttc tac aga cct tct gag tgt tgt gac acc ctc ctt tgt gac 8085
Val Phe Tyr Arg Pro Ser Glu Cys Cys Asp Thr Leu Leu Cys Asp
2650 2655 2660
atc gga gag tcc tcg tca agt gct gag gtt gaa gag cat agg acg 8130
Ile Gly Glu Ser Ser Ser Ser Ala Glu Val Glu Glu His Arg Thr
2665 2670 2675
att cgg gtc ctt gaa atg gtt gag gac tgg ctg cac cga ggg cca 8175
Ile Arg Val Leu Glu Met Val Glu Asp Trp Leu His Arg Gly Pro
2680 2685 2690
agg gaa ttt tgc gtg aag gtg ctc tgc ccc tac atg ccg aaa gtc 8220
Arg Glu Phe Cys Val Lys Val Leu Cys Pro Tyr Met Pro Lys Val
2695 2700 2705
ata gag aag atg gag ctg ctc caa cgc cgg tat ggg ggg gga ctg 8265
Ile Glu Lys Met Glu Leu Leu Gln Arg Arg Tyr Gly Gly Gly Leu
2710 2715 2720
gtc aga aac cca ctc tca cgg aat tcc acg cac gag atg tat tgg 8310
Val Arg Asn Pro Leu Ser Arg Asn Ser Thr His Glu Met Tyr Trp
2725 2730 2735
gtg agt cga gct tca ggc aat gtg gta cat tca gtg aat atg acc 8355
Val Ser Arg Ala Ser Gly Asn Val Val His Ser Val Asn Met Thr
2740 2745 2750
agc cag gtg ctc cta gga aga atg gaa aaa agg acc tgg aag gga 8400
Ser Gln Val Leu Leu Gly Arg Met Glu Lys Arg Thr Trp Lys Gly
2755 2760 2765
ccc caa tac gag gaa gat gta aac ttg gga agt gga acc agg gcg 8445
Pro Gln Tyr Glu Glu Asp Val Asn Leu Gly Ser Gly Thr Arg Ala
2770 2775 2780
gtg gga aaa ccc ctg ctc aac tca gac acc agt aaa atc aag aac 8490
Val Gly Lys Pro Leu Leu Asn Ser Asp Thr Ser Lys Ile Lys Asn
2785 2790 2795
agg att gaa cga ctc agg cgt gag tac agt tcg acg tgg cac cac 8535
Arg Ile Glu Arg Leu Arg Arg Glu Tyr Ser Ser Thr Trp His His
2800 2805 2810
gat gag aac cac cca tat aga acc tgg aac tat cac ggc agt tat 8580
Asp Glu Asn His Pro Tyr Arg Thr Trp Asn Tyr His Gly Ser Tyr
2815 2820 2825
gat gtg aag ccc aca ggc tcc gcc agt tcg ctg gtc aat gga gtg 8625
Asp Val Lys Pro Thr Gly Ser Ala Ser Ser Leu Val Asn Gly Val
2830 2835 2840
gtc agg ctc ctc tca aaa cca tgg gac acc atc acg aat gtt acc 8670
Val Arg Leu Leu Ser Lys Pro Trp Asp Thr Ile Thr Asn Val Thr
2845 2850 2855
acc atg gcc atg act gac act act ccc ttc ggg cag cag cga gtg 8715
Thr Met Ala Met Thr Asp Thr Thr Pro Phe Gly Gln Gln Arg Val
2860 2865 2870
ttc aaa gag aag gtg gac acg aaa gct cct gaa ccg cca gaa gga 8760
Phe Lys Glu Lys Val Asp Thr Lys Ala Pro Glu Pro Pro Glu Gly
2875 2880 2885
gtg aag tac gtg ctc aac gag acc acc aac tgg ttg tgg gcg ttt 8805
Val Lys Tyr Val Leu Asn Glu Thr Thr Asn Trp Leu Trp Ala Phe
2890 2895 2900
ttg gcc aga gaa aaa cgt ccc aga atg tgc tct cga gag gaa ttc 8850
Leu Ala Arg Glu Lys Arg Pro Arg Met Cys Ser Arg Glu Glu Phe
2905 2910 2915
ata aga aag gtc aac agc aat gca gct ttg ggt gcc atg ttt gaa 8895
Ile Arg Lys Val Asn Ser Asn Ala Ala Leu Gly Ala Met Phe Glu
2920 2925 2930
gag cag aat caa tgg agg agc gcc aga gaa gca gtt gaa gat cca 8940
Glu Gln Asn Gln Trp Arg Ser Ala Arg Glu Ala Val Glu Asp Pro
2935 2940 2945
aaa ttt tgg gag atg gtg gat gag gag cgc gag gca cat ctg cgg 8985
Lys Phe Trp Glu Met Val Asp Glu Glu Arg Glu Ala His Leu Arg
2950 2955 2960
ggg gaa tgt cac act tgc att tac aac atg atg gga aag aga gag 9030
Gly Glu Cys His Thr Cys Ile Tyr Asn Met Met Gly Lys Arg Glu
2965 2970 2975
aaa aaa ccc gga gag ttc gga aag gcc aag gga agc aga gcc att 9075
Lys Lys Pro Gly Glu Phe Gly Lys Ala Lys Gly Ser Arg Ala Ile
2980 2985 2990
tgg ttc atg tgg ctc gga gct cgc ttt ctg gag ttc gag gct ctg 9120
Trp Phe Met Trp Leu Gly Ala Arg Phe Leu Glu Phe Glu Ala Leu
2995 3000 3005
ggt ttt ctc aat gaa gac cac tgg ctt gga aga aag aac tca gga 9165
Gly Phe Leu Asn Glu Asp His Trp Leu Gly Arg Lys Asn Ser Gly
3010 3015 3020
gga ggt gtc gag ggc ttg ggc ctc caa aaa ctg ggt tac atc ctg 9210
Gly Gly Val Glu Gly Leu Gly Leu Gln Lys Leu Gly Tyr Ile Leu
3025 3030 3035
cgt gaa gtt ggc acc cgg cct ggg ggc aag atc tat gct gat gac 9255
Arg Glu Val Gly Thr Arg Pro Gly Gly Lys Ile Tyr Ala Asp Asp
3040 3045 3050
aca gct ggc tgg gac acc cgc atc acg aga gct gac ttg gaa aat 9300
Thr Ala Gly Trp Asp Thr Arg Ile Thr Arg Ala Asp Leu Glu Asn
3055 3060 3065
gaa gct aag gtg ctt gag ctg ctt gat ggg gaa cat cgg cgt ctt 9345
Glu Ala Lys Val Leu Glu Leu Leu Asp Gly Glu His Arg Arg Leu
3070 3075 3080
gcc agg gcc atc att gag ctc acc tat cgt cac aaa gtt gtg aaa 9390
Ala Arg Ala Ile Ile Glu Leu Thr Tyr Arg His Lys Val Val Lys
3085 3090 3095
gtg atg cgc ccg gct gct gat gga aga acc gtc atg gat gtt atc 9435
Val Met Arg Pro Ala Ala Asp Gly Arg Thr Val Met Asp Val Ile
3100 3105 3110
tcc aga gaa gat cag agg ggg agt gga caa gtt gtc acc tac gcc 9480
Ser Arg Glu Asp Gln Arg Gly Ser Gly Gln Val Val Thr Tyr Ala
3115 3120 3125
cta aac act ttc acc aac ctg gcc gtc cag ctg gtg agg atg atg 9525
Leu Asn Thr Phe Thr Asn Leu Ala Val Gln Leu Val Arg Met Met
3130 3135 3140
gaa ggg gaa gga gtg att ggc cca gat gat gtg gag aaa ctc aca 9570
Glu Gly Glu Gly Val Ile Gly Pro Asp Asp Val Glu Lys Leu Thr
3145 3150 3155
aaa ggg aaa gga ccc aaa gtc agg acc tgg ctg ttt gag aat ggg 9615
Lys Gly Lys Gly Pro Lys Val Arg Thr Trp Leu Phe Glu Asn Gly
3160 3165 3170
gaa gaa aga ctc agc cgc atg gct gtc agt gga gat gac tgt gtg 9660
Glu Glu Arg Leu Ser Arg Met Ala Val Ser Gly Asp Asp Cys Val
3175 3180 3185
gta aag ccc ctg gac gat cgc ttt gcc acc tcg ctc cac ttc ctc 9705
Val Lys Pro Leu Asp Asp Arg Phe Ala Thr Ser Leu His Phe Leu
3190 3195 3200
aat gct atg tca aag gtt cgc aaa gac atc caa gag tgg aaa ccg 9750
Asn Ala Met Ser Lys Val Arg Lys Asp Ile Gln Glu Trp Lys Pro
3205 3210 3215
tca act gga tgg tat gat tgg cag cag gtt cca ttt tgc tca aac 9795
Ser Thr Gly Trp Tyr Asp Trp Gln Gln Val Pro Phe Cys Ser Asn
3220 3225 3230
cat ttc act gaa ttg atc atg aaa gat gga aga aca ctg gtg gtt 9840
His Phe Thr Glu Leu Ile Met Lys Asp Gly Arg Thr Leu Val Val
3235 3240 3245
cca tgc cga gga cag gat gaa ttg gta ggc aga gct cgc ata tct 9885
Pro Cys Arg Gly Gln Asp Glu Leu Val Gly Arg Ala Arg Ile Ser
3250 3255 3260
cca ggg gcc gga tgg aac gtc cgc gac act gct tgt ctg gct aag 9930
Pro Gly Ala Gly Trp Asn Val Arg Asp Thr Ala Cys Leu Ala Lys
3265 3270 3275
tct tat gcc cag atg tgg ctg ctt ctg tac ttc cac aga aga gac 9975
Ser Tyr Ala Gln Met Trp Leu Leu Leu Tyr Phe His Arg Arg Asp
3280 3285 3290
ctg cgg ctc atg gcc aac gcc att tgc tcc gct gtc cct gtg aat 10020
Leu Arg Leu Met Ala Asn Ala Ile Cys Ser Ala Val Pro Val Asn
3295 3300 3305
tgg gtc cct acc gga aga acc acg tgg tcc atc cat gca gga gga 10065
Trp Val Pro Thr Gly Arg Thr Thr Trp Ser Ile His Ala Gly Gly
3310 3315 3320
gag tgg atg aca aca gag gac atg ttg gag gtc tgg aac cgt gtt 10110
Glu Trp Met Thr Thr Glu Asp Met Leu Glu Val Trp Asn Arg Val
3325 3330 3335
tgg ata gag gag aat gaa tgg atg gaa gac aaa acc cca gtg gag 10155
Trp Ile Glu Glu Asn Glu Trp Met Glu Asp Lys Thr Pro Val Glu
3340 3345 3350
aaa tgg agt gac gtc cca tat tca gga aaa cga gag gac atc tgg 10200
Lys Trp Ser Asp Val Pro Tyr Ser Gly Lys Arg Glu Asp Ile Trp
3355 3360 3365
tgt ggc agc ctg att ggc aca aga gcc cga gcc acg tgg gca gaa 10245
Cys Gly Ser Leu Ile Gly Thr Arg Ala Arg Ala Thr Trp Ala Glu
3370 3375 3380
aac atc cag gtg gct atc aac caa gtc aga gca atc atc gga gat 10290
Asn Ile Gln Val Ala Ile Asn Gln Val Arg Ala Ile Ile Gly Asp
3385 3390 3395
gag aag tat gtg gat tac atg agt tca cta aag aga tat gaa gac 10335
Glu Lys Tyr Val Asp Tyr Met Ser Ser Leu Lys Arg Tyr Glu Asp
3400 3405 3410
aca act ttg gtt gag gac aca gta ctg tag atatttaatc aattgtaaat 10385
Thr Thr Leu Val Glu Asp Thr Val Leu
3415 3420
agacaatata agtatgcata aaagtgtagt tttatagtag tatttagtgg tgttagtgta10445
aatagttaag aaaattttga ggagaaagtc aggccgggaa gttcccgcca ccggaagttg10505
agtagacggt gctgcctgcg actcaacccc aggaggactg ggtgaacaaa gccgcgaagt10565
gatccatgta agccctcaga accgtctcgg aaggaggacc ccacatgttg taacttcaaa10625
gcccaatgtc agaccacgct acggcgtgct actctgcgga gagtgcagtc tgcgatagtg10685
ccccaggagg actgggttaa caaaggcaaa ccaacgcccc acgcggccct agccccggta10745
atggtgttaa ccagggcgaa aggactagag gttagaggag accccgcggt ttaaagtgca10805
cggcccagcc tggctgaagc tgtaggtcag gggaaggact agaggttagt ggagaccccg10865
tgccacaaaa caccacaaca aaacagcata ttgacacctg ggatagacta ggagatcttc10925
tgctctgcac aaccagccac acggcacagt gcgccgacaa tggtggctgg tggtgcgaga10985
acacaggatc t 10996
<210> 14
<211> 3422
<212> PRT
<213> 人工序列
<220>
<223> 合成的构建体
<400> 14
Met Ser Lys Lys Pro Gly Gly Pro Gly Lys Ser Arg Ala Val Asn Met
1 5 10 15
Leu Lys Arg Gly Met Pro Arg Val Leu Ser Leu Ile Gly Leu Lys Arg
20 25 30
Ala Met Leu Ser Leu Ile Asp Gly Lys Gly Pro Ile Arg Phe Val Leu
35 40 45
Ala Leu Leu Ala Phe Phe Arg Phe Thr Ala Ile Ala Pro Thr Arg Ala
50 55 60
Val Leu Asp Arg Trp Arg Gly Val Asn Lys Gln Thr Ala Met Lys His
65 70 75 80
Leu Leu Ser Phe Lys Lys Glu Leu Gly Thr Leu Thr Ser Ala Ile Asn
85 90 95
Arg Arg Ser Ser Lys Gln Lys Lys Arg Ser Ala Gly Met Ile Ile Met
100 105 110
Leu Ile Pro Thr Val Met Ala Phe His Leu Thr Thr Arg Asn Gly Glu
115 120 125
Pro His Met Ile Val Ser Arg Gln Glu Lys Gly Lys Ser Leu Leu Phe
130 135 140
Lys Thr Glu Asp Gly Val Asn Met Cys Thr Leu Met Ala Met Asp Leu
145 150 155 160
Gly Glu Leu Cys Glu Asp Thr Ile Thr Tyr Lys Cys Pro Leu Leu Arg
165 170 175
Gln Asn Glu Pro Glu Asp Ile Asp Cys Trp Cys Asn Ser Thr Ser Thr
180 185 190
Trp Val Thr Tyr Gly Thr Cys Thr Thr Met Gly Glu His Arg Arg Glu
195 200 205
Lys Arg Ser Val Ala Leu Val Pro His Val Gly Met Gly Leu Glu Thr
210 215 220
Arg Thr Glu Thr Trp Met Ser Ser Glu Gly Ala Trp Lys His Val Gln
225 230 235 240
Arg Ile Glu Thr Trp Ile Leu Arg His Pro Gly Phe Thr Met Met Ala
245 250 255
Ala Ile Leu Ala Tyr Thr Ile Gly Thr Thr His Phe Gln Arg Ala Leu
260 265 270
Ile Phe Ile Leu Leu Thr Ala Val Thr Pro Ser Met Thr Met Arg Cys
275 280 285
Ile Gly Met Ser Asn Arg Asp Phe Val Glu Gly Val Ser Gly Gly Ser
290 295 300
Trp Val Asp Ile Val Leu Glu His Gly Ser Cys Val Thr Thr Met Ala
305 310 315 320
Lys Asn Lys Pro Thr Leu Asp Phe Glu Leu Ile Lys Thr Glu Ala Lys
325 330 335
Gln Pro Ala Thr Leu Arg Lys Tyr Cys Ile Glu Ala Lys Leu Thr Asn
340 345 350
Thr Thr Thr Glu Ser Arg Cys Pro Thr Gln Gly Glu Pro Ser Leu Asn
355 360 365
Glu Glu Gln Asp Lys Arg Phe Val Cys Lys His Ser Met Val Asp Arg
370 375 380
Gly Trp Gly Asn Gly Cys Gly Leu Phe Gly Lys Gly Gly Ile Val Thr
385 390 395 400
Cys Ala Met Phe Arg Cys Lys Lys Asn Met Glu Gly Lys Val Val Gln
405 410 415
Pro Glu Asn Leu Glu Tyr Thr Ile Val Ile Thr Pro His Ser Gly Glu
420 425 430
Glu His Ala Val Gly Asn Asp Thr Gly Lys His Gly Lys Glu Ile Lys
435 440 445
Ile Thr Pro Gln Ser Ser Ile Thr Glu Ala Glu Leu Thr Gly Tyr Gly
450 455 460
Thr Val Thr Met Glu Cys Ser Pro Arg Thr Gly Leu Asp Phe Asn Glu
465 470 475 480
Met Val Leu Leu Gln Met Glu Asp Lys Ala Trp Leu Val His Arg Gln
485 490 495
Trp Phe Leu Asp Leu Pro Leu Pro Trp Leu Pro Gly Ala Asp Thr Gln
500 505 510
Gly Ser Asn Trp Ile Gln Lys Glu Thr Leu Val Thr Phe Lys Asn Pro
515 520 525
His Ala Lys Lys Gln Asp Val Val Val Leu Gly Ser Gln Glu Gly Ala
530 535 540
Met His Thr Ala Leu Thr Gly Ala Thr Glu Ile Gln Met Ser Ser Gly
545 550 555 560
Asn Leu Leu Phe Thr Gly His Leu Lys Cys Arg Leu Arg Met Asp Lys
565 570 575
Leu Gln Leu Lys Gly Met Ser Tyr Ser Met Cys Thr Gly Lys Phe Lys
580 585 590
Val Val Lys Glu Ile Ala Glu Thr Gln His Gly Thr Ile Val Ile Arg
595 600 605
Val Gln Tyr Glu Gly Asp Gly Ser Pro Cys Lys Ile Pro Phe Glu Ile
610 615 620
Met Asp Leu Glu Lys Arg His Val Leu Gly Arg Leu Ile Thr Val Asn
625 630 635 640
Pro Ile Val Thr Glu Lys Asp Ser Pro Val Asn Ile Glu Ala Glu Pro
645 650 655
Pro Phe Gly Asp Ser Tyr Ile Ile Ile Gly Val Glu Pro Gly Gln Leu
660 665 670
Lys Leu Asn Trp Phe Lys Lys Gly Ser Ser Ile Gly Gln Met Phe Glu
675 680 685
Thr Thr Met Arg Gly Ala Lys Arg Met Ala Ile Leu Gly Asp Thr Ala
690 695 700
Trp Asp Phe Gly Ser Leu Gly Gly Val Phe Thr Ser Ile Gly Lys Ala
705 710 715 720
Leu His Gln Val Phe Gly Ala Ile Tyr Gly Ala Ala Phe Ser Gly Val
725 730 735
Ser Trp Thr Met Lys Ile Leu Ile Gly Val Ile Ile Thr Trp Ile Gly
740 745 750
Met Asn Ser Arg Ser Thr Ser Leu Ser Val Thr Leu Val Leu Val Gly
755 760 765
Ile Val Thr Leu Tyr Leu Gly Val Met Val Gln Ala Asp Ser Gly Cys
770 775 780
Ala Ile Asp Ile Ser Arg Gln Glu Leu Arg Cys Gly Ser Gly Val Phe
785 790 795 800
Ile His Asn Asp Val Glu Ala Trp Met Asp Arg Tyr Lys Tyr Tyr Pro
805 810 815
Glu Thr Pro Gln Gly Leu Ala Lys Ile Ile Gln Lys Ala His Lys Glu
820 825 830
Gly Val Cys Gly Leu Arg Ser Val Ser Arg Leu Glu His Gln Met Trp
835 840 845
Glu Ala Val Lys Asp Glu Leu Asn Thr Leu Leu Lys Glu Asn Gly Val
850 855 860
Asp Leu Ser Val Val Val Glu Lys Gln Glu Gly Met Tyr Lys Ser Ala
865 870 875 880
Pro Lys Arg Leu Thr Ala Thr Thr Glu Lys Leu Glu Ile Gly Trp Lys
885 890 895
Ala Trp Gly Lys Ser Ile Leu Phe Ala Pro Glu Leu Ala Asn Asn Thr
900 905 910
Phe Val Val Asp Gly Pro Glu Thr Lys Glu Cys Pro Thr Gln Asn Arg
915 920 925
Ala Trp Asn Ser Leu Glu Val Glu Asp Phe Gly Phe Gly Leu Thr Ser
930 935 940
Thr Arg Met Phe Leu Lys Val Arg Glu Ser Asn Thr Thr Glu Cys Asp
945 950 955 960
Ser Lys Ile Ile Gly Thr Ala Val Lys Asn Asn Leu Ala Ile His Ser
965 970 975
Asp Leu Ser Tyr Trp Ile Glu Ser Arg Leu Asn Asp Thr Trp Lys Leu
980 985 990
Glu Arg Ala Val Leu Gly Glu Val Lys Ser Cys Thr Trp Pro Glu Thr
995 1000 1005
His Thr Leu Trp Gly Asp Gly Ile Leu Glu Ser Asp Leu Ile Ile
1010 1015 1020
Pro Val Thr Leu Ala Gly Pro Arg Ser Asn His Asn Arg Arg Pro
1025 1030 1035
Gly Tyr Lys Thr Gln Asn Gln Gly Pro Trp Asp Glu Gly Arg Val
1040 1045 1050
Glu Ile Asp Phe Asp Tyr Cys Pro Gly Thr Thr Val Thr Leu Ser
1055 1060 1065
Glu Ser Cys Gly His Arg Gly Pro Ala Thr Arg Thr Thr Thr Glu
1070 1075 1080
Ser Gly Lys Leu Ile Thr Asp Trp Cys Cys Arg Ser Cys Thr Leu
1085 1090 1095
Pro Pro Leu Arg Tyr Gln Thr Asp Ser Gly Cys Trp Tyr Gly Met
1100 1105 1110
Glu Ile Arg Pro Gln Arg His Asp Glu Lys Thr Leu Val Gln Ser
1115 1120 1125
Gln Val Asn Ala Tyr Asn Ala Asp Met Ile Asp Pro Phe Gln Leu
1130 1135 1140
Gly Leu Leu Val Val Phe Leu Ala Thr Gln Glu Val Leu Arg Lys
1145 1150 1155
Arg Trp Thr Ala Lys Ile Ser Met Pro Ala Ile Leu Ile Ala Leu
1160 1165 1170
Leu Val Leu Val Phe Gly Gly Ile Thr Tyr Thr Asp Val Leu Arg
1175 1180 1185
Tyr Val Ile Leu Val Gly Ala Ala Phe Ala Glu Ser Asn Ser Gly
1190 1195 1200
Gly Asp Val Val His Leu Ala Leu Met Ala Thr Phe Lys Ile Gln
1205 1210 1215
Pro Val Phe Met Val Ala Ser Phe Leu Lys Ala Arg Trp Thr Asn
1220 1225 1230
Gln Glu Asn Ile Leu Leu Met Leu Ala Ala Val Phe Phe Gln Met
1235 1240 1245
Ala Tyr Tyr Asp Ala Arg Gln Ile Leu Leu Trp Glu Ile Pro Asp
1250 1255 1260
Val Leu Asn Ser Leu Ala Val Ala Trp Met Ile Leu Arg Ala Ile
1265 1270 1275
Thr Phe Thr Thr Thr Ser Asn Val Val Val Pro Leu Leu Ala Leu
1280 1285 1290
Leu Thr Pro Gly Leu Arg Cys Leu Asn Leu Asp Val Tyr Arg Ile
1295 1300 1305
Leu Leu Leu Met Val Gly Ile Gly Ser Leu Ile Arg Glu Lys Arg
1310 1315 1320
Ser Ala Ala Ala Lys Lys Lys Gly Ala Ser Leu Leu Cys Leu Ala
1325 1330 1335
Leu Ala Ser Thr Gly Leu Phe Asn Pro Met Ile Leu Ala Ala Gly
1340 1345 1350
Leu Ile Ala Cys Asp Pro Asn Arg Lys Arg Gly Trp Pro Ala Thr
1355 1360 1365
Glu Val Met Thr Ala Val Gly Leu Met Phe Ala Ile Val Gly Gly
1370 1375 1380
Leu Ala Glu Leu Asp Ile Asp Ser Met Ala Ile Pro Met Thr Ile
1385 1390 1395
Ala Gly Leu Met Phe Ala Ala Phe Val Ile Ser Gly Lys Ser Thr
1400 1405 1410
Asp Met Trp Ile Glu Arg Thr Ala Asp Ile Ser Trp Glu Ser Asp
1415 1420 1425
Ala Glu Ile Thr Gly Ser Ser Glu Arg Val Asp Val Arg Leu Asp
1430 1435 1440
Asp Asp Gly Asn Phe Gln Leu Met Asn Asp Pro Gly Ala Pro Trp
1445 1450 1455
Lys Ile Trp Met Leu Arg Met Val Cys Leu Ala Ile Ser Ala Tyr
1460 1465 1470
Thr Pro Trp Ala Ile Leu Pro Ser Val Val Gly Phe Trp Ile Thr
1475 1480 1485
Leu Gln Tyr Thr Lys Arg Gly Gly Val Leu Trp Asp Thr Pro Ser
1490 1495 1500
Pro Lys Glu Tyr Lys Lys Gly Asp Thr Thr Thr Gly Val Tyr Arg
1505 1510 1515
Ile Met Thr Arg Gly Leu Leu Gly Ser Tyr Gln Ala Gly Ala Gly
1520 1525 1530
Val Met Val Glu Gly Val Phe His Thr Leu Trp His Thr Thr Lys
1535 1540 1545
Gly Ala Ala Leu Met Ser Gly Glu Gly Arg Leu Asp Pro Tyr Trp
1550 1555 1560
Gly Ser Val Lys Glu Asp Arg Leu Cys Tyr Gly Gly Pro Trp Lys
1565 1570 1575
Leu Gln His Lys Trp Asn Gly Gln Asp Glu Val Gln Met Ile Val
1580 1585 1590
Val Glu Pro Gly Arg Asn Val Lys Asn Val Gln Thr Lys Pro Gly
1595 1600 1605
Val Phe Lys Thr Pro Glu Gly Glu Ile Gly Ala Val Thr Leu Asp
1610 1615 1620
Phe Pro Thr Gly Thr Ser Gly Ser Pro Ile Val Asp Lys Asn Gly
1625 1630 1635
Asp Val Ile Gly Leu Tyr Gly Asn Gly Val Ile Met Pro Asn Gly
1640 1645 1650
Ser Tyr Ile Ser Ala Ile Val Gln Gly Glu Arg Met Asp Glu Pro
1655 1660 1665
Ile Pro Ala Gly Phe Glu Pro Glu Met Leu Arg Lys Lys Gln Ile
1670 1675 1680
Thr Val Leu Asp Leu His Pro Gly Ala Gly Lys Thr Arg Arg Ile
1685 1690 1695
Leu Pro Gln Ile Ile Lys Glu Ala Ile Asn Arg Arg Leu Arg Thr
1700 1705 1710
Ala Val Leu Ala Pro Thr Arg Val Val Ala Ala Glu Met Ala Glu
1715 1720 1725
Ala Leu Arg Gly Leu Pro Ile Arg Tyr Gln Thr Ser Ala Val Pro
1730 1735 1740
Arg Glu His Asn Gly Asn Glu Ile Val Asp Val Met Cys His Ala
1745 1750 1755
Thr Leu Thr His Arg Leu Met Ser Pro His Arg Val Pro Asn Tyr
1760 1765 1770
Asn Leu Phe Val Met Asp Glu Ala His Phe Thr Asp Pro Ala Ser
1775 1780 1785
Ile Ala Ala Arg Gly Tyr Ile Ser Thr Lys Val Glu Leu Gly Glu
1790 1795 1800
Ala Ala Ala Ile Phe Met Thr Ala Thr Pro Pro Gly Thr Ser Asp
1805 1810 1815
Pro Phe Pro Glu Ser Asn Ser Pro Ile Ser Asp Leu Gln Thr Glu
1820 1825 1830
Ile Pro Asp Arg Ala Trp Asn Ser Gly Tyr Glu Trp Ile Thr Glu
1835 1840 1845
Tyr Thr Gly Lys Thr Val Trp Phe Val Pro Ser Val Lys Met Gly
1850 1855 1860
Asn Glu Ile Ala Leu Cys Leu Gln Arg Ala Gly Lys Lys Val Val
1865 1870 1875
Gln Leu Asn Arg Lys Ser Tyr Glu Thr Glu Tyr Pro Lys Cys Lys
1880 1885 1890
Asn Asp Asp Trp Asp Phe Val Ile Thr Thr Asp Ile Ser Glu Met
1895 1900 1905
Gly Ala Asn Phe Lys Ala Ser Arg Val Ile Asp Ser Arg Lys Ser
1910 1915 1920
Val Lys Pro Thr Ile Ile Thr Glu Gly Glu Gly Arg Val Ile Leu
1925 1930 1935
Gly Glu Pro Ser Ala Val Thr Ala Ala Ser Ala Ala Gln Arg Arg
1940 1945 1950
Gly Arg Ile Gly Arg Asn Pro Ser Gln Val Gly Asp Glu Tyr Cys
1955 1960 1965
Tyr Gly Gly His Thr Asn Glu Asp Asp Ser Asn Phe Ala His Trp
1970 1975 1980
Thr Glu Ala Arg Ile Met Leu Asp Asn Ile Asn Met Pro Asn Gly
1985 1990 1995
Leu Ile Ala Gln Phe Tyr Gln Pro Glu Arg Glu Lys Val Tyr Thr
2000 2005 2010
Met Asp Gly Glu Tyr Arg Leu Arg Gly Glu Glu Arg Lys Asn Phe
2015 2020 2025
Leu Glu Leu Leu Arg Thr Ala Asp Leu Pro Val Trp Leu Ala Tyr
2030 2035 2040
Lys Val Ala Ala Ala Gly Val Ser Tyr His Asp Arg Arg Trp Cys
2045 2050 2055
Phe Asp Gly Pro Arg Thr Asn Thr Ile Leu Glu Asp Asn Asn Glu
2060 2065 2070
Val Glu Val Ile Thr Lys Leu Gly Glu Arg Lys Ile Leu Arg Pro
2075 2080 2085
Arg Trp Ile Asp Ala Arg Val Tyr Ser Asp His Gln Ala Leu Lys
2090 2095 2100
Ala Phe Lys Asp Phe Ala Ser Gly Lys Arg Ser Gln Ile Gly Leu
2105 2110 2115
Ile Glu Val Leu Gly Lys Met Pro Glu His Phe Met Gly Lys Thr
2120 2125 2130
Trp Glu Ala Leu Asp Thr Met Tyr Val Val Ala Thr Ala Glu Lys
2135 2140 2145
Gly Gly Arg Ala His Arg Met Ala Leu Glu Glu Leu Pro Asp Ala
2150 2155 2160
Leu Gln Thr Ile Ala Leu Ile Ala Leu Leu Ser Val Met Thr Met
2165 2170 2175
Gly Val Phe Phe Leu Leu Met Gln Arg Lys Gly Ile Gly Lys Ile
2180 2185 2190
Gly Leu Gly Gly Ala Val Leu Gly Val Ala Thr Phe Phe Cys Trp
2195 2200 2205
Met Ala Glu Val Pro Gly Thr Lys Ile Ala Gly Met Leu Leu Leu
2210 2215 2220
Ser Leu Leu Leu Met Ile Val Leu Ile Pro Glu Pro Glu Lys Gln
2225 2230 2235
Arg Ser Gln Thr Asp Asn Gln Leu Ala Val Phe Leu Ile Cys Val
2240 2245 2250
Met Thr Leu Val Ser Ala Val Ala Ala Asn Glu Met Gly Trp Leu
2255 2260 2265
Asp Lys Thr Lys Ser Asp Ile Ser Ser Leu Phe Gly Gln Arg Ile
2270 2275 2280
Glu Val Lys Glu Asn Phe Ser Met Gly Glu Phe Leu Leu Asp Leu
2285 2290 2295
Arg Pro Ala Thr Ala Trp Ser Leu Tyr Ala Val Thr Thr Ala Val
2300 2305 2310
Leu Thr Pro Leu Leu Lys His Leu Ile Thr Ser Asp Tyr Ile Asn
2315 2320 2325
Thr Ser Leu Thr Ser Ile Asn Val Gln Ala Ser Ala Leu Phe Thr
2330 2335 2340
Leu Ala Arg Gly Phe Pro Phe Val Asp Val Gly Val Ser Ala Leu
2345 2350 2355
Leu Leu Ala Ala Gly Cys Trp Gly Gln Val Thr Leu Thr Val Thr
2360 2365 2370
Val Thr Ala Ala Thr Leu Leu Phe Cys His Tyr Ala Tyr Met Val
2375 2380 2385
Pro Gly Trp Gln Ala Glu Ala Met Arg Ser Ala Gln Arg Arg Thr
2390 2395 2400
Ala Ala Gly Ile Met Lys Asn Ala Val Val Asp Gly Ile Val Ala
2405 2410 2415
Thr Asp Val Pro Glu Leu Glu Arg Thr Thr Pro Ile Met Gln Lys
2420 2425 2430
Lys Val Gly Gln Ile Met Leu Ile Leu Val Ser Leu Ala Ala Val
2435 2440 2445
Val Val Asn Pro Ser Val Lys Thr Val Arg Glu Ala Gly Ile Leu
2450 2455 2460
Ile Thr Ala Ala Ala Val Thr Leu Trp Glu Asn Gly Ala Ser Ser
2465 2470 2475
Val Trp Asn Ala Thr Thr Ala Ile Gly Leu Cys His Ile Met Arg
2480 2485 2490
Gly Gly Trp Leu Ser Cys Leu Ser Ile Thr Trp Thr Leu Ile Lys
2495 2500 2505
Asn Met Glu Lys Pro Gly Leu Lys Arg Gly Gly Ala Lys Gly Arg
2510 2515 2520
Thr Leu Gly Glu Val Trp Lys Glu Arg Leu Asn Gln Met Thr Lys
2525 2530 2535
Glu Glu Phe Thr Arg Tyr Arg Lys Glu Ala Ile Ile Glu Val Asp
2540 2545 2550
Arg Ser Ala Ala Lys His Ala Arg Lys Glu Gly Asn Val Thr Gly
2555 2560 2565
Gly His Pro Val Ser Arg Gly Thr Ala Lys Leu Arg Trp Leu Val
2570 2575 2580
Glu Arg Arg Phe Leu Glu Pro Val Gly Lys Val Ile Asp Leu Gly
2585 2590 2595
Cys Gly Arg Gly Gly Trp Cys Tyr Tyr Met Ala Thr Gln Lys Arg
2600 2605 2610
Val Gln Glu Val Arg Gly Tyr Thr Lys Gly Gly Pro Gly His Glu
2615 2620 2625
Glu Pro Gln Leu Val Gln Ser Tyr Gly Trp Asn Ile Val Thr Met
2630 2635 2640
Lys Ser Gly Val Asp Val Phe Tyr Arg Pro Ser Glu Cys Cys Asp
2645 2650 2655
Thr Leu Leu Cys Asp Ile Gly Glu Ser Ser Ser Ser Ala Glu Val
2660 2665 2670
Glu Glu His Arg Thr Ile Arg Val Leu Glu Met Val Glu Asp Trp
2675 2680 2685
Leu His Arg Gly Pro Arg Glu Phe Cys Val Lys Val Leu Cys Pro
2690 2695 2700
Tyr Met Pro Lys Val Ile Glu Lys Met Glu Leu Leu Gln Arg Arg
2705 2710 2715
Tyr Gly Gly Gly Leu Val Arg Asn Pro Leu Ser Arg Asn Ser Thr
2720 2725 2730
His Glu Met Tyr Trp Val Ser Arg Ala Ser Gly Asn Val Val His
2735 2740 2745
Ser Val Asn Met Thr Ser Gln Val Leu Leu Gly Arg Met Glu Lys
2750 2755 2760
Arg Thr Trp Lys Gly Pro Gln Tyr Glu Glu Asp Val Asn Leu Gly
2765 2770 2775
Ser Gly Thr Arg Ala Val Gly Lys Pro Leu Leu Asn Ser Asp Thr
2780 2785 2790
Ser Lys Ile Lys Asn Arg Ile Glu Arg Leu Arg Arg Glu Tyr Ser
2795 2800 2805
Ser Thr Trp His His Asp Glu Asn His Pro Tyr Arg Thr Trp Asn
2810 2815 2820
Tyr His Gly Ser Tyr Asp Val Lys Pro Thr Gly Ser Ala Ser Ser
2825 2830 2835
Leu Val Asn Gly Val Val Arg Leu Leu Ser Lys Pro Trp Asp Thr
2840 2845 2850
Ile Thr Asn Val Thr Thr Met Ala Met Thr Asp Thr Thr Pro Phe
2855 2860 2865
Gly Gln Gln Arg Val Phe Lys Glu Lys Val Asp Thr Lys Ala Pro
2870 2875 2880
Glu Pro Pro Glu Gly Val Lys Tyr Val Leu Asn Glu Thr Thr Asn
2885 2890 2895
Trp Leu Trp Ala Phe Leu Ala Arg Glu Lys Arg Pro Arg Met Cys
2900 2905 2910
Ser Arg Glu Glu Phe Ile Arg Lys Val Asn Ser Asn Ala Ala Leu
2915 2920 2925
Gly Ala Met Phe Glu Glu Gln Asn Gln Trp Arg Ser Ala Arg Glu
2930 2935 2940
Ala Val Glu Asp Pro Lys Phe Trp Glu Met Val Asp Glu Glu Arg
2945 2950 2955
Glu Ala His Leu Arg Gly Glu Cys His Thr Cys Ile Tyr Asn Met
2960 2965 2970
Met Gly Lys Arg Glu Lys Lys Pro Gly Glu Phe Gly Lys Ala Lys
2975 2980 2985
Gly Ser Arg Ala Ile Trp Phe Met Trp Leu Gly Ala Arg Phe Leu
2990 2995 3000
Glu Phe Glu Ala Leu Gly Phe Leu Asn Glu Asp His Trp Leu Gly
3005 3010 3015
Arg Lys Asn Ser Gly Gly Gly Val Glu Gly Leu Gly Leu Gln Lys
3020 3025 3030
Leu Gly Tyr Ile Leu Arg Glu Val Gly Thr Arg Pro Gly Gly Lys
3035 3040 3045
Ile Tyr Ala Asp Asp Thr Ala Gly Trp Asp Thr Arg Ile Thr Arg
3050 3055 3060
Ala Asp Leu Glu Asn Glu Ala Lys Val Leu Glu Leu Leu Asp Gly
3065 3070 3075
Glu His Arg Arg Leu Ala Arg Ala Ile Ile Glu Leu Thr Tyr Arg
3080 3085 3090
His Lys Val Val Lys Val Met Arg Pro Ala Ala Asp Gly Arg Thr
3095 3100 3105
Val Met Asp Val Ile Ser Arg Glu Asp Gln Arg Gly Ser Gly Gln
3110 3115 3120
Val Val Thr Tyr Ala Leu Asn Thr Phe Thr Asn Leu Ala Val Gln
3125 3130 3135
Leu Val Arg Met Met Glu Gly Glu Gly Val Ile Gly Pro Asp Asp
3140 3145 3150
Val Glu Lys Leu Thr Lys Gly Lys Gly Pro Lys Val Arg Thr Trp
3155 3160 3165
Leu Phe Glu Asn Gly Glu Glu Arg Leu Ser Arg Met Ala Val Ser
3170 3175 3180
Gly Asp Asp Cys Val Val Lys Pro Leu Asp Asp Arg Phe Ala Thr
3185 3190 3195
Ser Leu His Phe Leu Asn Ala Met Ser Lys Val Arg Lys Asp Ile
3200 3205 3210
Gln Glu Trp Lys Pro Ser Thr Gly Trp Tyr Asp Trp Gln Gln Val
3215 3220 3225
Pro Phe Cys Ser Asn His Phe Thr Glu Leu Ile Met Lys Asp Gly
3230 3235 3240
Arg Thr Leu Val Val Pro Cys Arg Gly Gln Asp Glu Leu Val Gly
3245 3250 3255
Arg Ala Arg Ile Ser Pro Gly Ala Gly Trp Asn Val Arg Asp Thr
3260 3265 3270
Ala Cys Leu Ala Lys Ser Tyr Ala Gln Met Trp Leu Leu Leu Tyr
3275 3280 3285
Phe His Arg Arg Asp Leu Arg Leu Met Ala Asn Ala Ile Cys Ser
3290 3295 3300
Ala Val Pro Val Asn Trp Val Pro Thr Gly Arg Thr Thr Trp Ser
3305 3310 3315
Ile His Ala Gly Gly Glu Trp Met Thr Thr Glu Asp Met Leu Glu
3320 3325 3330
Val Trp Asn Arg Val Trp Ile Glu Glu Asn Glu Trp Met Glu Asp
3335 3340 3345
Lys Thr Pro Val Glu Lys Trp Ser Asp Val Pro Tyr Ser Gly Lys
3350 3355 3360
Arg Glu Asp Ile Trp Cys Gly Ser Leu Ile Gly Thr Arg Ala Arg
3365 3370 3375
Ala Thr Trp Ala Glu Asn Ile Gln Val Ala Ile Asn Gln Val Arg
3380 3385 3390
Ala Ile Ile Gly Asp Glu Lys Tyr Val Asp Tyr Met Ser Ser Leu
3395 3400 3405
Lys Arg Tyr Glu Asp Thr Thr Leu Val Glu Asp Thr Val Leu
3410 3415 3420
<210> 15
<211> 11002
<212> DNA
<213> 人工序列
<220>
<223> 具有 E345 His 到 Leu突变的WN/DEN3嵌合体(BE345)
<220>
<221> CDS
<222> (97)..(10371)
<400> 15
agtagttcgc ctgtgtgagc tgacaaactt agtagtgttt gtgaggatta acaacaatta 60
acacagtgcg agctgtttct tagcacgaag atctcg atg tct aag aaa cca gga 114
Met Ser Lys Lys Pro Gly
1 5
ggg ccc ggc aag agc cgg gct gtc aat atg cta aaa cgc gga atg ccc 162
Gly Pro Gly Lys Ser Arg Ala Val Asn Met Leu Lys Arg Gly Met Pro
10 15 20
cgc gtg ttg tcc ttg att gga ctg aag agg gct atg ttg agc ctg atc 210
Arg Val Leu Ser Leu Ile Gly Leu Lys Arg Ala Met Leu Ser Leu Ile
25 30 35
gac ggc aag ggg cca ata cga ttt gtg ttg gct ctc ttg gcg ttc ttc 258
Asp Gly Lys Gly Pro Ile Arg Phe Val Leu Ala Leu Leu Ala Phe Phe
40 45 50
agg ttc aca gca att gct ccg acc cga gca gtg ctg gat cga tgg aga 306
Arg Phe Thr Ala Ile Ala Pro Thr Arg Ala Val Leu Asp Arg Trp Arg
55 60 65 70
ggt gtg aac aaa caa aca gcg atg aaa cac ctt ctg agt ttt aag aag 354
Gly Val Asn Lys Gln Thr Ala Met Lys His Leu Leu Ser Phe Lys Lys
75 80 85
gaa cta ggg acc ttg acc agt gct atc aat cgg cgg agt tcg aaa caa 402
Glu Leu Gly Thr Leu Thr Ser Ala Ile Asn Arg Arg Ser Ser Lys Gln
90 95 100
aag aaa aga gga gga aag acc gga att ctc tgt ctc atg atg atg tta 450
Lys Lys Arg Gly Gly Lys Thr Gly Ile Leu Cys Leu Met Met Met Leu
105 110 115
cca gca aca ctt gct ttc cac tta act tca cga gat gga gag ccg cgc 498
Pro Ala Thr Leu Ala Phe His Leu Thr Ser Arg Asp Gly Glu Pro Arg
120 125 130
atg att gtg ggg aag aat gaa aga gga aaa tcc cta ctt ttc aag aca 546
Met Ile Val Gly Lys Asn Glu Arg Gly Lys Ser Leu Leu Phe Lys Thr
135 140 145 150
gcc tct gga atc aac atg tgc aca ctc ata gcc atg gat ctg gga gag 594
Ala Ser Gly Ile Asn Met Cys Thr Leu Ile Ala Met Asp Leu Gly Glu
155 160 165
atg tgt gat gac acg gtc act tac aaa tgc ccc cac att acc gaa gtg 642
Met Cys Asp Asp Thr Val Thr Tyr Lys Cys Pro His Ile Thr Glu Val
170 175 180
gag cct gaa gac att gac tgc tgg tgc aac ctt aca tcg aca tgg gtg 690
Glu Pro Glu Asp Ile Asp Cys Trp Cys Asn Leu Thr Ser Thr Trp Val
185 190 195
act tat gga aca tgc aat caa gct gga gag cat aga cgc gat aag aga 738
Thr Tyr Gly Thr Cys Asn Gln Ala Gly Glu His Arg Arg Asp Lys Arg
200 205 210
tca gtg gcg tta gct ccc cat gtt ggc atg gga ctg gac aca cgc act 786
Ser Val Ala Leu Ala Pro His Val Gly Met Gly Leu Asp Thr Arg Thr
215 220 225 230
caa acc tgg atg tcg gct gaa gga gct tgg aga caa gtc gag aag gta 834
Gln Thr Trp Met Ser Ala Glu Gly Ala Trp Arg Gln Val Glu Lys Val
235 240 245
gag aca tgg gcc ctt agg cac cca ggg ttt acc ata cta gcc cta ttt 882
Glu Thr Trp Ala Leu Arg His Pro Gly Phe Thr Ile Leu Ala Leu Phe
250 255 260
ctt gcc cat tac ata ggc act tcc ttg acc cag aaa gtg gtt att ttt 930
Leu Ala His Tyr Ile Gly Thr Ser Leu Thr Gln Lys Val Val Ile Phe
265 270 275
ata cta tta atg ctg gtt acc cca tcc atg aca atg aga tgt gta gga 978
Ile Leu Leu Met Leu Val Thr Pro Ser Met Thr Met Arg Cys Val Gly
280 285 290
gta gga aac aga gat ttt gtg gaa ggc cta tcg gga gct acg tgg gtt 1026
Val Gly Asn Arg Asp Phe Val Glu Gly Leu Ser Gly Ala Thr Trp Val
295 300 305 310
gac gtg gtg ctc gag cac ggt ggg tgt gtg act acc atg gct aag aac 1074
Asp Val Val Leu Glu His Gly Gly Cys Val Thr Thr Met Ala Lys Asn
315 320 325
aag ccc acg ctg gac ata gag ctt cag aag acc gag gcc acc caa ctg 1122
Lys Pro Thr Leu Asp Ile Glu Leu Gln Lys Thr Glu Ala Thr Gln Leu
330 335 340
gcg acc cta agg aag cta tgc att gag gga aaa att acc aac ata aca 1170
Ala Thr Leu Arg Lys Leu Cys Ile Glu Gly Lys Ile Thr Asn Ile Thr
345 350 355
acc gac tca aga tgt ccc acc caa ggg gaa gcg att tta cct gag gag 1218
Thr Asp Ser Arg Cys Pro Thr Gln Gly Glu Ala Ile Leu Pro Glu Glu
360 365 370
cag gac cag aac tac gtg tgt aag cat aca tac gtg gac aga ggc tgg 1266
Gln Asp Gln Asn Tyr Val Cys Lys His Thr Tyr Val Asp Arg Gly Trp
375 380 385 390
gga aac ggt tgt ggt ttg ttt ggc aag gga agc ttg gtg aca tgc gcg 1314
Gly Asn Gly Cys Gly Leu Phe Gly Lys Gly Ser Leu Val Thr Cys Ala
395 400 405
aaa ttt caa tgt tta gaa tca ata gag gga aaa gtg gtg caa cat gag 1362
Lys Phe Gln Cys Leu Glu Ser Ile Glu Gly Lys Val Val Gln His Glu
410 415 420
aac ctc aaa tac acc gtc atc atc aca gtg cac aca gga gac caa cac 1410
Asn Leu Lys Tyr Thr Val Ile Ile Thr Val His Thr Gly Asp Gln His
425 430 435
cag gtg gga aat gaa acg cag gga gtc acg gct gag ata aca ccc cag 1458
Gln Val Gly Asn Glu Thr Gln Gly Val Thr Ala Glu Ile Thr Pro Gln
440 445 450
gca tca acc gct gaa gcc att tta cct gaa tat gga acc ctc ggg cta 1506
Ala Ser Thr Ala Glu Ala Ile Leu Pro Glu Tyr Gly Thr Leu Gly Leu
455 460 465 470
gaa tgc tca cca cgg aca ggt ttg gat ttc aat gaa atg atc tca ttg 1554
Glu Cys Ser Pro Arg Thr Gly Leu Asp Phe Asn Glu Met Ile Ser Leu
475 480 485
aca atg aag aac aaa gca tgg atg gta cat aga caa tgg ttc ttt gac 1602
Thr Met Lys Asn Lys Ala Trp Met Val His Arg Gln Trp Phe Phe Asp
490 495 500
tta ccc cta cca tgg aca tca gga gct aca gca gaa aca cca act tgg 1650
Leu Pro Leu Pro Trp Thr Ser Gly Ala Thr Ala Glu Thr Pro Thr Trp
505 510 515
aac agg aaa gag ctt ctt gtg aca ttt aaa aat gca cat gca aaa aag 1698
Asn Arg Lys Glu Leu Leu Val Thr Phe Lys Asn Ala His Ala Lys Lys
520 525 530
caa gaa gta gtt gtt ctt gga tca caa gag gga gca atg cat aca gca 1746
Gln Glu Val Val Val Leu Gly Ser Gln Glu Gly Ala Met His Thr Ala
535 540 545 550
ctg aca gga gct aca gag atc caa acc tca gga ggc aca agt atc ttt 1794
Leu Thr Gly Ala Thr Glu Ile Gln Thr Ser Gly Gly Thr Ser Ile Phe
555 560 565
gcg ggg cac tta aaa tgt aga ctc aag atg gac aaa ttg gaa ctc aag 1842
Ala Gly His Leu Lys Cys Arg Leu Lys Met Asp Lys Leu Glu Leu Lys
570 575 580
ggg atg agc tat gca atg tgc ttg agt agc ttt gtg ttg aag aaa gaa 1890
Gly Met Ser Tyr Ala Met Cys Leu Ser Ser Phe Val Leu Lys Lys Glu
585 590 595
gtc tcc gaa acg cag cat ggg aca ata ctc att aag gtt gag tac aaa 1938
Val Ser Glu Thr Gln His Gly Thr Ile Leu Ile Lys Val Glu Tyr Lys
600 605 610
ggg gaa gat gca ccc tgc aag att cct ttc tcc acg gag gat gga caa 1986
Gly Glu Asp Ala Pro Cys Lys Ile Pro Phe Ser Thr Glu Asp Gly Gln
615 620 625 630
gga aaa gct ctc aat ggc aga ctg atc aca gcc aat cca gtg gtg acc 2034
Gly Lys Ala Leu Asn Gly Arg Leu Ile Thr Ala Asn Pro Val Val Thr
635 640 645
aag aag gag gag cct gtc aac att gag gct gaa cct cct ttt gga gaa 2082
Lys Lys Glu Glu Pro Val Asn Ile Glu Ala Glu Pro Pro Phe Gly Glu
650 655 660
agt aac ata gta att gga att gga gac aaa gcc ctg aaa atc aac tgg 2130
Ser Asn Ile Val Ile Gly Ile Gly Asp Lys Ala Leu Lys Ile Asn Trp
665 670 675
tac aag aag gga agc tcg att ggg aag atg ttc gag gcc act gcc aga 2178
Tyr Lys Lys Gly Ser Ser Ile Gly Lys Met Phe Glu Ala Thr Ala Arg
680 685 690
ggt gca agg cgc atg gcc atc ttg gga gac aca gcc tgg gac ttt gga 2226
Gly Ala Arg Arg Met Ala Ile Leu Gly Asp Thr Ala Trp Asp Phe Gly
695 700 705 710
tca gtg ggt ggt gtt ttg aat tca tta ggg aaa atg gtc cac caa ata 2274
Ser Val Gly Gly Val Leu Asn Ser Leu Gly Lys Met Val His Gln Ile
715 720 725
ttt ggg agt gct tac aca gcc cta ttt ggt gga gtc tcc tgg atg atg 2322
Phe Gly Ser Ala Tyr Thr Ala Leu Phe Gly Gly Val Ser Trp Met Met
730 735 740
aaa att gga ata ggt gtc ctc tta acc tgg ata ggg ttg aac tca aaa 2370
Lys Ile Gly Ile Gly Val Leu Leu Thr Trp Ile Gly Leu Asn Ser Lys
745 750 755
aat act tct atg tca ttt tca tgc atc gcg ata gga atc att aca ctc 2418
Asn Thr Ser Met Ser Phe Ser Cys Ile Ala Ile Gly Ile Ile Thr Leu
760 765 770
tat ctg gga gcc gtg gtg caa gct gac tcc gga tgt gcc ata gac atc 2466
Tyr Leu Gly Ala Val Val Gln Ala Asp Ser Gly Cys Ala Ile Asp Ile
775 780 785 790
agc cgg caa gag ctg aga tgt gga agt gga gtg ttc ata cac aat gat 2514
Ser Arg Gln Glu Leu Arg Cys Gly Ser Gly Val Phe Ile His Asn Asp
795 800 805
gtg gag gct tgg atg gac cgg tac aag tat tac cct gaa acg cca caa 2562
Val Glu Ala Trp Met Asp Arg Tyr Lys Tyr Tyr Pro Glu Thr Pro Gln
810 815 820
ggc cta gcc aag atc att cag aaa gct cat aag gaa gga gtg tgc ggt 2610
Gly Leu Ala Lys Ile Ile Gln Lys Ala His Lys Glu Gly Val Cys Gly
825 830 835
cta cga tca gtt tcc aga ctg gag cat caa atg tgg gaa gca gtg aag 2658
Leu Arg Ser Val Ser Arg Leu Glu His Gln Met Trp Glu Ala Val Lys
840 845 850
gac gag ctg aac act ctt ttg aag gag aat ggt gtg gac ctt agt gtc 2706
Asp Glu Leu Asn Thr Leu Leu Lys Glu Asn Gly Val Asp Leu Ser Val
855 860 865 870
gtg gtt gag aaa cag gag gga atg tac aag tca gca cct aaa cgc ctc 2754
Val Val Glu Lys Gln Glu Gly Met Tyr Lys Ser Ala Pro Lys Arg Leu
875 880 885
acc gcc acc acg gaa aaa ttg gaa att ggc tgg aag gcc tgg gga aag 2802
Thr Ala Thr Thr Glu Lys Leu Glu Ile Gly Trp Lys Ala Trp Gly Lys
890 895 900
agt att tta ttt gca cca gaa ctc gcc aac aac acc ttt gtg gtt gat 2850
Ser Ile Leu Phe Ala Pro Glu Leu Ala Asn Asn Thr Phe Val Val Asp
905 910 915
ggt ccg gag acc aag gaa tgt ccg act cag aat cgc gct tgg aat agc 2898
Gly Pro Glu Thr Lys Glu Cys Pro Thr Gln Asn Arg Ala Trp Asn Ser
920 925 930
tta gaa gtg gag gat ttt gga ttt ggt ctc acc agc act cgg atg ttc 2946
Leu Glu Val Glu Asp Phe Gly Phe Gly Leu Thr Ser Thr Arg Met Phe
935 940 945 950
ctg aag gtc aga gag agc aac aca act gaa tgt gac tcg aag atc att 2994
Leu Lys Val Arg Glu Ser Asn Thr Thr Glu Cys Asp Ser Lys Ile Ile
955 960 965
gga acg gct gtc aag aac aac ttg gcg atc cac agt gac ctg tcc tat 3042
Gly Thr Ala Val Lys Asn Asn Leu Ala Ile His Ser Asp Leu Ser Tyr
970 975 980
tgg att gaa agc agg ctc aat gat acg tgg aag ctt gaa agg gca gtt 3090
Trp Ile Glu Ser Arg Leu Asn Asp Thr Trp Lys Leu Glu Arg Ala Val
985 990 995
ctg ggt gaa gtc aaa tca tgt acg tgg cct gag acg cat acc ttg 3135
Leu Gly Glu Val Lys Ser Cys Thr Trp Pro Glu Thr His Thr Leu
1000 1005 1010
tgg ggc gat gga atc ctt gag agt gac ttg ata ata cca gtc aca 3180
Trp Gly Asp Gly Ile Leu Glu Ser Asp Leu Ile Ile Pro Val Thr
1015 1020 1025
ctg gcg gga cca cga agc aat cac aat cgg aga cct ggg tac aag 3225
Leu Ala Gly Pro Arg Ser Asn His Asn Arg Arg Pro Gly Tyr Lys
1030 1035 1040
aca caa aac cag ggc cca tgg gac gaa ggc cgg gta gag att gac 3270
Thr Gln Asn Gln Gly Pro Trp Asp Glu Gly Arg Val Glu Ile Asp
1045 1050 1055
ttc gat tac tgc cca gga act acg gtc acc ctg agt gag agc tgc 3315
Phe Asp Tyr Cys Pro Gly Thr Thr Val Thr Leu Ser Glu Ser Cys
1060 1065 1070
gga cac cgt gga cct gcc act cgc acc acc aca gag agc gga aag 3360
Gly His Arg Gly Pro Ala Thr Arg Thr Thr Thr Glu Ser Gly Lys
1075 1080 1085
ttg ata aca gat tgg tgc tgc agg agc tgc acc tta cca cca ctg 3405
Leu Ile Thr Asp Trp Cys Cys Arg Ser Cys Thr Leu Pro Pro Leu
1090 1095 1100
cgc tac caa act gac agc ggc tgt tgg tat ggt atg gag atc aga 3450
Arg Tyr Gln Thr Asp Ser Gly Cys Trp Tyr Gly Met Glu Ile Arg
1105 1110 1115
cca cag aga cat gat gaa aag acc ctc gtg cag tca caa gtg aat 3495
Pro Gln Arg His Asp Glu Lys Thr Leu Val Gln Ser Gln Val Asn
1120 1125 1130
gct tat aat gct gat atg att gac cct ttt cag ttg ggc ctt ctg 3540
Ala Tyr Asn Ala Asp Met Ile Asp Pro Phe Gln Leu Gly Leu Leu
1135 1140 1145
gtc gtg ttc ttg gcc acc cag gag gtc ctt cgc aag agg tgg aca 3585
Val Val Phe Leu Ala Thr Gln Glu Val Leu Arg Lys Arg Trp Thr
1150 1155 1160
gcc aag atc agc atg cca gct ata ctg att gct ctg cta gtc ctg 3630
Ala Lys Ile Ser Met Pro Ala Ile Leu Ile Ala Leu Leu Val Leu
1165 1170 1175
gtg ttt ggg ggc att act tac act gat gtg tta cgc tat gtc atc 3675
Val Phe Gly Gly Ile Thr Tyr Thr Asp Val Leu Arg Tyr Val Ile
1180 1185 1190
ttg gtg ggg gca gct ttc gca gaa tct aat tcg gga gga gac gtg 3720
Leu Val Gly Ala Ala Phe Ala Glu Ser Asn Ser Gly Gly Asp Val
1195 1200 1205
gta cac ttg gcg ctc atg gcg acc ttc aag ata caa cca gtg ttt 3765
Val His Leu Ala Leu Met Ala Thr Phe Lys Ile Gln Pro Val Phe
1210 1215 1220
atg gtg gca tcg ttt ctc aaa gcg aga tgg acc aac cag gag aac 3810
Met Val Ala Ser Phe Leu Lys Ala Arg Trp Thr Asn Gln Glu Asn
1225 1230 1235
att ttg ttg atg ttg gcg gct gtt ttc ttt caa atg gct tat tac 3855
Ile Leu Leu Met Leu Ala Ala Val Phe Phe Gln Met Ala Tyr Tyr
1240 1245 1250
gat gcc cgc caa att ctg ctc tgg gag atc cct gat gtg ttg aat 3900
Asp Ala Arg Gln Ile Leu Leu Trp Glu Ile Pro Asp Val Leu Asn
1255 1260 1265
tca ctg gcg gta gct tgg atg ata ctg aga gcc ata aca ttc aca 3945
Ser Leu Ala Val Ala Trp Met Ile Leu Arg Ala Ile Thr Phe Thr
1270 1275 1280
acg aca tca aac gtg gtt gtt ccg ctg cta gcc ctg cta aca ccc 3990
Thr Thr Ser Asn Val Val Val Pro Leu Leu Ala Leu Leu Thr Pro
1285 1290 1295
ggg ctg aga tgc ttg aat ctg gat gtg tac agg ata ctg ctg ttg 4035
Gly Leu Arg Cys Leu Asn Leu Asp Val Tyr Arg Ile Leu Leu Leu
1300 1305 1310
atg gtc gga ata ggc agc ttg atc agg gag aag agg agt gca gct 4080
Met Val Gly Ile Gly Ser Leu Ile Arg Glu Lys Arg Ser Ala Ala
1315 1320 1325
gca aaa aag aaa gga gca agt ctg cta tgc ttg gct cta gcc tca 4125
Ala Lys Lys Lys Gly Ala Ser Leu Leu Cys Leu Ala Leu Ala Ser
1330 1335 1340
aca gga ctt ttc aac ccc atg atc ctt gct gct gga ctg att gca 4170
Thr Gly Leu Phe Asn Pro Met Ile Leu Ala Ala Gly Leu Ile Ala
1345 1350 1355
tgt gat ccc aac cgt aaa cgc gga tgg ccc gca act gaa gtg atg 4215
Cys Asp Pro Asn Arg Lys Arg Gly Trp Pro Ala Thr Glu Val Met
1360 1365 1370
aca gct gtc ggc cta atg ttt gcc atc gtc gga ggg ctg gca gag 4260
Thr Ala Val Gly Leu Met Phe Ala Ile Val Gly Gly Leu Ala Glu
1375 1380 1385
ctt gac att gac tcc atg gcc att cca atg act atc gcg ggg ctc 4305
Leu Asp Ile Asp Ser Met Ala Ile Pro Met Thr Ile Ala Gly Leu
1390 1395 1400
atg ttt gct gct ttc gtg att tct ggg aaa tca aca gat atg tgg 4350
Met Phe Ala Ala Phe Val Ile Ser Gly Lys Ser Thr Asp Met Trp
1405 1410 1415
att gag aga acg gcg gac att tcc tgg gaa agt gat gca gaa att 4395
Ile Glu Arg Thr Ala Asp Ile Ser Trp Glu Ser Asp Ala Glu Ile
1420 1425 1430
aca ggc tcg agc gaa aga gtt gat gtg cgg ctt gat gat gat gga 4440
Thr Gly Ser Ser Glu Arg Val Asp Val Arg Leu Asp Asp Asp Gly
1435 1440 1445
aac ttc cag ctc atg aat gat cca gga gca cct tgg aag ata tgg 4485
Asn Phe Gln Leu Met Asn Asp Pro Gly Ala Pro Trp Lys Ile Trp
1450 1455 1460
atg ctc aga atg gtc tgt ctc gcg att agt gcg tac acc ccc tgg 4530
Met Leu Arg Met Val Cys Leu Ala Ile Ser Ala Tyr Thr Pro Trp
1465 1470 1475
gca atc ttg ccc tca gta gtt gga ttt tgg ata act ctc caa tac 4575
Ala Ile Leu Pro Ser Val Val Gly Phe Trp Ile Thr Leu Gln Tyr
1480 1485 1490
aca aag aga gga ggc gtg ttg tgg gac act ccc tca cca aag gag 4620
Thr Lys Arg Gly Gly Val Leu Trp Asp Thr Pro Ser Pro Lys Glu
1495 1500 1505
tac aaa aag ggg gac acg acc acc ggc gtc tac agg atc atg act 4665
Tyr Lys Lys Gly Asp Thr Thr Thr Gly Val Tyr Arg Ile Met Thr
1510 1515 1520
cgt ggg ctg ctc ggc agt tat caa gca gga gcg ggc gtg atg gtt 4710
Arg Gly Leu Leu Gly Ser Tyr Gln Ala Gly Ala Gly Val Met Val
1525 1530 1535
gaa ggt gtt ttc cac acc ctt tgg cat aca aca aaa gga gcc gct 4755
Glu Gly Val Phe His Thr Leu Trp His Thr Thr Lys Gly Ala Ala
1540 1545 1550
ttg atg agc gga gag ggc cgc ctg gac cca tac tgg ggc agt gtc 4800
Leu Met Ser Gly Glu Gly Arg Leu Asp Pro Tyr Trp Gly Ser Val
1555 1560 1565
aag gag gat cga ctt tgt tac gga gga ccc tgg aaa ttg cag cac 4845
Lys Glu Asp Arg Leu Cys Tyr Gly Gly Pro Trp Lys Leu Gln His
1570 1575 1580
aag tgg aac ggg cag gat gag gtg cag atg att gtg gtg gaa cct 4890
Lys Trp Asn Gly Gln Asp Glu Val Gln Met Ile Val Val Glu Pro
1585 1590 1595
ggc agg aac gtt aag aac gtc cag acg aaa cca ggg gtg ttc aaa 4935
Gly Arg Asn Val Lys Asn Val Gln Thr Lys Pro Gly Val Phe Lys
1600 1605 1610
aca cct gaa gga gaa atc ggg gcc gtg act ttg gac ttc ccc act 4980
Thr Pro Glu Gly Glu Ile Gly Ala Val Thr Leu Asp Phe Pro Thr
1615 1620 1625
gga aca tca ggc tca cca ata gtg gac aaa aac ggt gat gtg att 5025
Gly Thr Ser Gly Ser Pro Ile Val Asp Lys Asn Gly Asp Val Ile
1630 1635 1640
ggg ctt tat ggc aat gga gtc ata atg ccc aac ggc tca tac ata 5070
Gly Leu Tyr Gly Asn Gly Val Ile Met Pro Asn Gly Ser Tyr Ile
1645 1650 1655
agc gcg ata gtg cag ggt gaa agg atg gat gag cca atc cca gcc 5115
Ser Ala Ile Val Gln Gly Glu Arg Met Asp Glu Pro Ile Pro Ala
1660 1665 1670
gga ttc gaa cct gag atg ctg agg aaa aaa cag atc act gta ctg 5160
Gly Phe Glu Pro Glu Met Leu Arg Lys Lys Gln Ile Thr Val Leu
1675 1680 1685
gat ctc cat ccc ggc gcc ggt aaa aca agg agg att ctg cca cag 5205
Asp Leu His Pro Gly Ala Gly Lys Thr Arg Arg Ile Leu Pro Gln
1690 1695 1700
atc atc aaa gag gcc ata aac aga aga ctg aga aca gcc gtg cta 5250
Ile Ile Lys Glu Ala Ile Asn Arg Arg Leu Arg Thr Ala Val Leu
1705 1710 1715
gca cca acc agg gtt gtg gct gct gag atg gct gaa gca ctg aga 5295
Ala Pro Thr Arg Val Val Ala Ala Glu Met Ala Glu Ala Leu Arg
1720 1725 1730
gga ctg ccc atc cgg tac cag aca tcc gca gtg ccc aga gaa cat 5340
Gly Leu Pro Ile Arg Tyr Gln Thr Ser Ala Val Pro Arg Glu His
1735 1740 1745
aat gga aat gag att gtt gat gtc atg tgt cat gct acc ctc acc 5385
Asn Gly Asn Glu Ile Val Asp Val Met Cys His Ala Thr Leu Thr
1750 1755 1760
cac agg ctg atg tct cct cac agg gtg ccg aac tac aac ctg ttc 5430
His Arg Leu Met Ser Pro His Arg Val Pro Asn Tyr Asn Leu Phe
1765 1770 1775
gtg atg gat gag gct cat ttc acc gac cca gct agc att gca gca 5475
Val Met Asp Glu Ala His Phe Thr Asp Pro Ala Ser Ile Ala Ala
1780 1785 1790
aga ggt tac att tcc aca aag gtc gag cta ggg gag gcg gcg gca 5520
Arg Gly Tyr Ile Ser Thr Lys Val Glu Leu Gly Glu Ala Ala Ala
1795 1800 1805
ata ttc atg aca gcc acc cca cca ggc act tca gat cca ttc cca 5565
Ile Phe Met Thr Ala Thr Pro Pro Gly Thr Ser Asp Pro Phe Pro
1810 1815 1820
gag tcc aat tca cca att tcc gac tta cag act gag atc ccg gat 5610
Glu Ser Asn Ser Pro Ile Ser Asp Leu Gln Thr Glu Ile Pro Asp
1825 1830 1835
cga gct tgg aac tct gga tac gaa tgg atc aca gaa tac acc ggg 5655
Arg Ala Trp Asn Ser Gly Tyr Glu Trp Ile Thr Glu Tyr Thr Gly
1840 1845 1850
aag acg gtt tgg ttt gtg cct agt gtc aag atg ggg aat gag att 5700
Lys Thr Val Trp Phe Val Pro Ser Val Lys Met Gly Asn Glu Ile
1855 1860 1865
gcc ctt tgc cta caa cgt gct gga aag aaa gta gtc caa ttg aac 5745
Ala Leu Cys Leu Gln Arg Ala Gly Lys Lys Val Val Gln Leu Asn
1870 1875 1880
aga aag tcg tac gag acg gag tac cca aaa tgt aag aac gat gat 5790
Arg Lys Ser Tyr Glu Thr Glu Tyr Pro Lys Cys Lys Asn Asp Asp
1885 1890 1895
tgg gac ttt gtt atc aca aca gac ata tct gaa atg ggg gct aac 5835
Trp Asp Phe Val Ile Thr Thr Asp Ile Ser Glu Met Gly Ala Asn
1900 1905 1910
ttc aag gcg agc agg gtg att gac agc cgg aag agt gtg aaa cca 5880
Phe Lys Ala Ser Arg Val Ile Asp Ser Arg Lys Ser Val Lys Pro
1915 1920 1925
acc atc ata aca gaa gga gaa ggg aga gtg atc ctg gga gaa cca 5925
Thr Ile Ile Thr Glu Gly Glu Gly Arg Val Ile Leu Gly Glu Pro
1930 1935 1940
tct gca gtg aca gca gct agt gcc gcc cag aga cgt gga cgt atc 5970
Ser Ala Val Thr Ala Ala Ser Ala Ala Gln Arg Arg Gly Arg Ile
1945 1950 1955
ggt aga aat ccg tcg caa gtt ggt gat gag tac tgt tat ggg ggg 6015
Gly Arg Asn Pro Ser Gln Val Gly Asp Glu Tyr Cys Tyr Gly Gly
1960 1965 1970
cac acg aat gaa gac gac tcg aac ttc gcc cat tgg act gag gca 6060
His Thr Asn Glu Asp Asp Ser Asn Phe Ala His Trp Thr Glu Ala
1975 1980 1985
cga atc atg ctg gac aac atc aac atg cca aac gga ctg atc gct 6105
Arg Ile Met Leu Asp Asn Ile Asn Met Pro Asn Gly Leu Ile Ala
1990 1995 2000
caa ttc tac caa cca gag cgt gag aag gta tat acc atg gat ggg 6150
Gln Phe Tyr Gln Pro Glu Arg Glu Lys Val Tyr Thr Met Asp Gly
2005 2010 2015
gaa tac cgg ctc aga gga gaa gag aga aaa aac ttt ctg gaa ctg 6195
Glu Tyr Arg Leu Arg Gly Glu Glu Arg Lys Asn Phe Leu Glu Leu
2020 2025 2030
ttg agg act gca gat ctg cca gtt tgg ctg gct tac aag gtt gca 6240
Leu Arg Thr Ala Asp Leu Pro Val Trp Leu Ala Tyr Lys Val Ala
2035 2040 2045
gcg gct gga gtg tca tac cac gac cgg agg tgg tgc ttt gat ggt 6285
Ala Ala Gly Val Ser Tyr His Asp Arg Arg Trp Cys Phe Asp Gly
2050 2055 2060
cct agg aca aac aca att tta gaa gac aac aac gaa gtg gaa gtc 6330
Pro Arg Thr Asn Thr Ile Leu Glu Asp Asn Asn Glu Val Glu Val
2065 2070 2075
atc acg aag ctt ggt gaa agg aag att ctg agg ccg cgc tgg att 6375
Ile Thr Lys Leu Gly Glu Arg Lys Ile Leu Arg Pro Arg Trp Ile
2080 2085 2090
gac gcc agg gtg tac tcg gat cac cag gca cta aag gcg ttc aag 6420
Asp Ala Arg Val Tyr Ser Asp His Gln Ala Leu Lys Ala Phe Lys
2095 2100 2105
gac ttc gcc tcg gga aaa cgt tct cag ata ggg ctc att gag gtt 6465
Asp Phe Ala Ser Gly Lys Arg Ser Gln Ile Gly Leu Ile Glu Val
2110 2115 2120
ctg gga aag atg cct gag cac ttc atg ggg aag aca tgg gaa gca 6510
Leu Gly Lys Met Pro Glu His Phe Met Gly Lys Thr Trp Glu Ala
2125 2130 2135
ctt gac acc atg tac gtt gtg gcc act gca gag aaa gga gga aga 6555
Leu Asp Thr Met Tyr Val Val Ala Thr Ala Glu Lys Gly Gly Arg
2140 2145 2150
gct cac aga atg gcc ctg gag gaa ctg cca gat gct ctt cag aca 6600
Ala His Arg Met Ala Leu Glu Glu Leu Pro Asp Ala Leu Gln Thr
2155 2160 2165
att gcc ttg att gcc tta ttg agt gtg atg acc atg gga gta ttc 6645
Ile Ala Leu Ile Ala Leu Leu Ser Val Met Thr Met Gly Val Phe
2170 2175 2180
ttc ctc ctc atg cag cgg aag ggc att gga aag ata ggt ttg gga 6690
Phe Leu Leu Met Gln Arg Lys Gly Ile Gly Lys Ile Gly Leu Gly
2185 2190 2195
ggc gct gtc ttg gga gtc gcg acc ttt ttc tgt tgg atg gct gaa 6735
Gly Ala Val Leu Gly Val Ala Thr Phe Phe Cys Trp Met Ala Glu
2200 2205 2210
gtt cca gga acg aag atc gcc gga atg ttg ctg ctc tcc ctt ctc 6780
Val Pro Gly Thr Lys Ile Ala Gly Met Leu Leu Leu Ser Leu Leu
2215 2220 2225
ttg atg att gtg cta att cct gag cca gag aag caa cgt tcg cag 6825
Leu Met Ile Val Leu Ile Pro Glu Pro Glu Lys Gln Arg Ser Gln
2230 2235 2240
aca gac aac cag cta gcc gtg ttc ctg att tgt gtc atg acc ctt 6870
Thr Asp Asn Gln Leu Ala Val Phe Leu Ile Cys Val Met Thr Leu
2245 2250 2255
gtg agc gca gtg gca gcc aac gag atg ggt tgg cta gat aag acc 6915
Val Ser Ala Val Ala Ala Asn Glu Met Gly Trp Leu Asp Lys Thr
2260 2265 2270
aag agt gac ata agc agt ttg ttt ggg caa aga att gag gtc aag 6960
Lys Ser Asp Ile Ser Ser Leu Phe Gly Gln Arg Ile Glu Val Lys
2275 2280 2285
gag aat ttc agc atg gga gag ttt ctt ttg gac ttg agg cct gca 7005
Glu Asn Phe Ser Met Gly Glu Phe Leu Leu Asp Leu Arg Pro Ala
2290 2295 2300
aca gcc tgg tca ctg tac gct gtg aca aca gcg gtc ctc act cca 7050
Thr Ala Trp Ser Leu Tyr Ala Val Thr Thr Ala Val Leu Thr Pro
2305 2310 2315
ctg cta aag cat ttg atc acg tca gat tac atc aac acc tca ttg 7095
Leu Leu Lys His Leu Ile Thr Ser Asp Tyr Ile Asn Thr Ser Leu
2320 2325 2330
acc tca ata aac gtt cag gca agt gca cta ttc aca ctc gcg cga 7140
Thr Ser Ile Asn Val Gln Ala Ser Ala Leu Phe Thr Leu Ala Arg
2335 2340 2345
ggc ttc ccc ttc gtc gat gtt gga gtg tcg gct ctc ctg cta gca 7185
Gly Phe Pro Phe Val Asp Val Gly Val Ser Ala Leu Leu Leu Ala
2350 2355 2360
gcc gga tgc tgg gga caa gtc acc ctc acc gtt acg gta aca gcg 7230
Ala Gly Cys Trp Gly Gln Val Thr Leu Thr Val Thr Val Thr Ala
2365 2370 2375
gca aca ctc ctt ttt tgc cac tat gcc tac atg gtt ccc ggt tgg 7275
Ala Thr Leu Leu Phe Cys His Tyr Ala Tyr Met Val Pro Gly Trp
2380 2385 2390
caa gct gag gca atg cgc tca gcc cag cgg cgg aca gcg gcc gga 7320
Gln Ala Glu Ala Met Arg Ser Ala Gln Arg Arg Thr Ala Ala Gly
2395 2400 2405
atc atg aag aac gct gta gtg gat ggc atc gtg gcc acg gac gtc 7365
Ile Met Lys Asn Ala Val Val Asp Gly Ile Val Ala Thr Asp Val
2410 2415 2420
cca gaa tta gag cgc acc aca ccc atc atg cag aag aaa gtt gga 7410
Pro Glu Leu Glu Arg Thr Thr Pro Ile Met Gln Lys Lys Val Gly
2425 2430 2435
cag atc atg ctg atc ttg gtg tct cta gct gca gta gta gtg aac 7455
Gln Ile Met Leu Ile Leu Val Ser Leu Ala Ala Val Val Val Asn
2440 2445 2450
ccg tct gtg aag aca gta cga gaa gcc gga att ttg atc acg gcc 7500
Pro Ser Val Lys Thr Val Arg Glu Ala Gly Ile Leu Ile Thr Ala
2455 2460 2465
gca gcg gtg acg ctt tgg gag aat gga gca agc tct gtt tgg aac 7545
Ala Ala Val Thr Leu Trp Glu Asn Gly Ala Ser Ser Val Trp Asn
2470 2475 2480
gca aca act gcc atc gga ctc tgc cac atc atg cgt ggg ggt tgg 7590
Ala Thr Thr Ala Ile Gly Leu Cys His Ile Met Arg Gly Gly Trp
2485 2490 2495
ttg tca tgt cta tcc ata aca tgg aca ctc ata aag aac atg gaa 7635
Leu Ser Cys Leu Ser Ile Thr Trp Thr Leu Ile Lys Asn Met Glu
2500 2505 2510
aaa cca gga cta aaa aga ggt ggg gca aaa gga cgc acc ttg gga 7680
Lys Pro Gly Leu Lys Arg Gly Gly Ala Lys Gly Arg Thr Leu Gly
2515 2520 2525
gag gtt tgg aaa gaa aga ctc aac cag atg aca aaa gaa gag ttc 7725
Glu Val Trp Lys Glu Arg Leu Asn Gln Met Thr Lys Glu Glu Phe
2530 2535 2540
act agg tac cgc aaa gag gcc atc atc gaa gtc gat cgc tca gcg 7770
Thr Arg Tyr Arg Lys Glu Ala Ile Ile Glu Val Asp Arg Ser Ala
2545 2550 2555
gca aaa cac gcc agg aaa gaa ggc aat gtc act gga ggg cat cca 7815
Ala Lys His Ala Arg Lys Glu Gly Asn Val Thr Gly Gly His Pro
2560 2565 2570
gtc tct agg ggc aca gca aaa ctg aga tgg ctg gtc gaa cgg agg 7860
Val Ser Arg Gly Thr Ala Lys Leu Arg Trp Leu Val Glu Arg Arg
2575 2580 2585
ttt ctc gaa ccg gtc gga aaa gtg att gac ctt gga tgt gga aga 7905
Phe Leu Glu Pro Val Gly Lys Val Ile Asp Leu Gly Cys Gly Arg
2590 2595 2600
ggc ggt tgg tgt tac tat atg gca acc caa aaa aga gtc caa gaa 7950
Gly Gly Trp Cys Tyr Tyr Met Ala Thr Gln Lys Arg Val Gln Glu
2605 2610 2615
gtc aga ggg tac aca aag ggc ggt ccc gga cat gaa gag ccc caa 7995
Val Arg Gly Tyr Thr Lys Gly Gly Pro Gly His Glu Glu Pro Gln
2620 2625 2630
cta gtg caa agt tat gga tgg aac att gtc acc atg aag agt gga 8040
Leu Val Gln Ser Tyr Gly Trp Asn Ile Val Thr Met Lys Ser Gly
2635 2640 2645
gtg gat gtg ttc tac aga cct tct gag tgt tgt gac acc ctc ctt 8085
Val Asp Val Phe Tyr Arg Pro Ser Glu Cys Cys Asp Thr Leu Leu
2650 2655 2660
tgt gac atc gga gag tcc tcg tca agt gct gag gtt gaa gag cat 8130
Cys Asp Ile Gly Glu Ser Ser Ser Ser Ala Glu Val Glu Glu His
2665 2670 2675
agg acg att cgg gtc ctt gaa atg gtt gag gac tgg ctg cac cga 8175
Arg Thr Ile Arg Val Leu Glu Met Val Glu Asp Trp Leu His Arg
2680 2685 2690
ggg cca agg gaa ttt tgc gtg aag gtg ctc tgc ccc tac atg ccg 8220
Gly Pro Arg Glu Phe Cys Val Lys Val Leu Cys Pro Tyr Met Pro
2695 2700 2705
aaa gtc ata gag aag atg gag ctg ctc caa cgc cgg tat ggg ggg 8265
Lys Val Ile Glu Lys Met Glu Leu Leu Gln Arg Arg Tyr Gly Gly
2710 2715 2720
gga ctg gtc aga aac cca ctc tca cgg aat tcc acg cac gag atg 8310
Gly Leu Val Arg Asn Pro Leu Ser Arg Asn Ser Thr His Glu Met
2725 2730 2735
tat tgg gtg agt cga gct tca ggc aat gtg gta cat tca gtg aat 8355
Tyr Trp Val Ser Arg Ala Ser Gly Asn Val Val His Ser Val Asn
2740 2745 2750
atg acc agc cag gtg ctc cta gga aga atg gaa aaa agg acc tgg 8400
Met Thr Ser Gln Val Leu Leu Gly Arg Met Glu Lys Arg Thr Trp
2755 2760 2765
aag gga ccc caa tac gag gaa gat gta aac ttg gga agt gga acc 8445
Lys Gly Pro Gln Tyr Glu Glu Asp Val Asn Leu Gly Ser Gly Thr
2770 2775 2780
agg gcg gtg gga aaa ccc ctg ctc aac tca gac acc agt aaa atc 8490
Arg Ala Val Gly Lys Pro Leu Leu Asn Ser Asp Thr Ser Lys Ile
2785 2790 2795
aag aac agg att gaa cga ctc agg cgt gag tac agt tcg acg tgg 8535
Lys Asn Arg Ile Glu Arg Leu Arg Arg Glu Tyr Ser Ser Thr Trp
2800 2805 2810
cac cac gat gag aac cac cca tat aga acc tgg aac tat cac ggc 8580
His His Asp Glu Asn His Pro Tyr Arg Thr Trp Asn Tyr His Gly
2815 2820 2825
agt tat gat gtg aag ccc aca ggc tcc gcc agt tcg ctg gtc aat 8625
Ser Tyr Asp Val Lys Pro Thr Gly Ser Ala Ser Ser Leu Val Asn
2830 2835 2840
gga gtg gtc agg ctc ctc tca aaa cca tgg gac acc atc acg aat 8670
Gly Val Val Arg Leu Leu Ser Lys Pro Trp Asp Thr Ile Thr Asn
2845 2850 2855
gtt acc acc atg gcc atg act gac act act ccc ttc ggg cag cag 8715
Val Thr Thr Met Ala Met Thr Asp Thr Thr Pro Phe Gly Gln Gln
2860 2865 2870
cga gtg ttc aaa gag aag gtg gac acg aaa gct cct gaa ccg cca 8760
Arg Val Phe Lys Glu Lys Val Asp Thr Lys Ala Pro Glu Pro Pro
2875 2880 2885
gaa gga gtg aag tac gtg ctc aac gag acc acc aac tgg ttg tgg 8805
Glu Gly Val Lys Tyr Val Leu Asn Glu Thr Thr Asn Trp Leu Trp
2890 2895 2900
gcg ttt ttg gcc aga gaa aaa cgt ccc aga atg tgc tct cga gag 8850
Ala Phe Leu Ala Arg Glu Lys Arg Pro Arg Met Cys Ser Arg Glu
2905 2910 2915
gaa ttc ata aga aag gtc aac agc aat gca gct ttg ggt gcc atg 8895
Glu Phe Ile Arg Lys Val Asn Ser Asn Ala Ala Leu Gly Ala Met
2920 2925 2930
ttt gaa gag cag aat caa tgg agg agc gcc aga gaa gca gtt gaa 8940
Phe Glu Glu Gln Asn Gln Trp Arg Ser Ala Arg Glu Ala Val Glu
2935 2940 2945
gat cca aaa ttt tgg gag atg gtg gat gag gag cgc gag gca cat 8985
Asp Pro Lys Phe Trp Glu Met Val Asp Glu Glu Arg Glu Ala His
2950 2955 2960
ctg cgg ggg gaa tgt cac act tgc att tac aac atg atg gga aag 9030
Leu Arg Gly Glu Cys His Thr Cys Ile Tyr Asn Met Met Gly Lys
2965 2970 2975
aga gag aaa aaa ccc gga gag ttc gga aag gcc aag gga agc aga 9075
Arg Glu Lys Lys Pro Gly Glu Phe Gly Lys Ala Lys Gly Ser Arg
2980 2985 2990
gcc att tgg ttc atg tgg ctc gga gct cgc ttt ctg gag ttc gag 9120
Ala Ile Trp Phe Met Trp Leu Gly Ala Arg Phe Leu Glu Phe Glu
2995 3000 3005
gct ctg ggt ttt ctc aat gaa gac cac tgg ctt gga aga aag aac 9165
Ala Leu Gly Phe Leu Asn Glu Asp His Trp Leu Gly Arg Lys Asn
3010 3015 3020
tca gga gga ggt gtc gag ggc ttg ggc ctc caa aaa ctg ggt tac 9210
Ser Gly Gly Gly Val Glu Gly Leu Gly Leu Gln Lys Leu Gly Tyr
3025 3030 3035
atc ctg cgt gaa gtt ggc acc cgg cct ggg ggc aag atc tat gct 9255
Ile Leu Arg Glu Val Gly Thr Arg Pro Gly Gly Lys Ile Tyr Ala
3040 3045 3050
gat gac aca gct ggc tgg gac acc cgc atc acg aga gct gac ttg 9300
Asp Asp Thr Ala Gly Trp Asp Thr Arg Ile Thr Arg Ala Asp Leu
3055 3060 3065
gaa aat gaa gct aag gtg ctt gag ctg ctt gat ggg gaa cat cgg 9345
Glu Asn Glu Ala Lys Val Leu Glu Leu Leu Asp Gly Glu His Arg
3070 3075 3080
cgt ctt gcc agg gcc atc att gag ctc acc tat cgt cac aaa gtt 9390
Arg Leu Ala Arg Ala Ile Ile Glu Leu Thr Tyr Arg His Lys Val
3085 3090 3095
gtg aaa gtg atg cgc ccg gct gct gat gga aga acc gtc atg gat 9435
Val Lys Val Met Arg Pro Ala Ala Asp Gly Arg Thr Val Met Asp
3100 3105 3110
gtt atc tcc aga gaa gat cag agg ggg agt gga caa gtt gtc acc 9480
Val Ile Ser Arg Glu Asp Gln Arg Gly Ser Gly Gln Val Val Thr
3115 3120 3125
tac gcc cta aac act ttc acc aac ctg gcc gtc cag ctg gtg agg 9525
Tyr Ala Leu Asn Thr Phe Thr Asn Leu Ala Val Gln Leu Val Arg
3130 3135 3140
atg atg gaa ggg gaa gga gtg att ggc cca gat gat gtg gag aaa 9570
Met Met Glu Gly Glu Gly Val Ile Gly Pro Asp Asp Val Glu Lys
3145 3150 3155
ctc aca aaa ggg aaa gga ccc aaa gtc agg acc tgg ctg ttt gag 9615
Leu Thr Lys Gly Lys Gly Pro Lys Val Arg Thr Trp Leu Phe Glu
3160 3165 3170
aat ggg gaa gaa aga ctc agc cgc atg gct gtc agt gga gat gac 9660
Asn Gly Glu Glu Arg Leu Ser Arg Met Ala Val Ser Gly Asp Asp
3175 3180 3185
tgt gtg gta aag ccc ctg gac gat cgc ttt gcc acc tcg ctc cac 9705
Cys Val Val Lys Pro Leu Asp Asp Arg Phe Ala Thr Ser Leu His
3190 3195 3200
ttc ctc aat gct atg tca aag gtt cgc aaa gac atc caa gag tgg 9750
Phe Leu Asn Ala Met Ser Lys Val Arg Lys Asp Ile Gln Glu Trp
3205 3210 3215
aaa ccg tca act gga tgg tat gat tgg cag cag gtt cca ttt tgc 9795
Lys Pro Ser Thr Gly Trp Tyr Asp Trp Gln Gln Val Pro Phe Cys
3220 3225 3230
tca aac cat ttc act gaa ttg atc atg aaa gat gga aga aca ctg 9840
Ser Asn His Phe Thr Glu Leu Ile Met Lys Asp Gly Arg Thr Leu
3235 3240 3245
gtg gtt cca tgc cga gga cag gat gaa ttg gta ggc aga gct cgc 9885
Val Val Pro Cys Arg Gly Gln Asp Glu Leu Val Gly Arg Ala Arg
3250 3255 3260
ata tct cca ggg gcc gga tgg aac gtc cgc gac act gct tgt ctg 9930
Ile Ser Pro Gly Ala Gly Trp Asn Val Arg Asp Thr Ala Cys Leu
3265 3270 3275
gct aag tct tat gcc cag atg tgg ctg ctt ctg tac ttc cac aga 9975
Ala Lys Ser Tyr Ala Gln Met Trp Leu Leu Leu Tyr Phe His Arg
3280 3285 3290
aga gac ctg cgg ctc atg gcc aac gcc att tgc tcc gct gtc cct 10020
Arg Asp Leu Arg Leu Met Ala Asn Ala Ile Cys Ser Ala Val Pro
3295 3300 3305
gtg aat tgg gtc cct acc gga aga acc acg tgg tcc atc cat gca 10065
Val Asn Trp Val Pro Thr Gly Arg Thr Thr Trp Ser Ile His Ala
3310 3315 3320
gga gga gag tgg atg aca aca gag gac atg ttg gag gtc tgg aac 10110
Gly Gly Glu Trp Met Thr Thr Glu Asp Met Leu Glu Val Trp Asn
3325 3330 3335
cgt gtt tgg ata gag gag aat gaa tgg atg gaa gac aaa acc cca 10155
Arg Val Trp Ile Glu Glu Asn Glu Trp Met Glu Asp Lys Thr Pro
3340 3345 3350
gtg gag aaa tgg agt gac gtc cca tat tca gga aaa cga gag gac 10200
Val Glu Lys Trp Ser Asp Val Pro Tyr Ser Gly Lys Arg Glu Asp
3355 3360 3365
atc tgg tgt ggc agc ctg att ggc aca aga gcc cga gcc acg tgg 10245
Ile Trp Cys Gly Ser Leu Ile Gly Thr Arg Ala Arg Ala Thr Trp
3370 3375 3380
gca gaa aac atc cag gtg gct atc aac caa gtc aga gca atc atc 10290
Ala Glu Asn Ile Gln Val Ala Ile Asn Gln Val Arg Ala Ile Ile
3385 3390 3395
gga gat gag aag tat gtg gat tac atg agt tca cta aag aga tat 10335
Gly Asp Glu Lys Tyr Val Asp Tyr Met Ser Ser Leu Lys Arg Tyr
3400 3405 3410
gaa gac aca act ttg gtt gag gac aca gta ctg tag atatttaatc 10381
Glu Asp Thr Thr Leu Val Glu Asp Thr Val Leu
3415 3420
aattgtaaat agacaatata agtatgcata aaagtgtagt tttatagtag tatttagtgg10441
tgttagtgta aatagttaag aaaattttga ggagaaagtc aggccgggaa gttcccgcca10501
ccggaagttg agtagacggt gctgcctgcg actcaacccc aggaggactg ggtgaacaaa10561
gccgcgaagt gatccatgta agccctcaga accgtctcgg aaggaggacc ccacatgttg10621
taacttcaaa gcccaatgtc agaccacgct acggcgtgct actctgcgga gagtgcagtc10681
tgcgatagtg ccccaggagg actgggttaa caaaggcaaa ccaacgcccc acgcggccct10741
agccccggta atggtgttaa ccagggcgaa aggactagag gttagaggag accccgcggt10801
ttaaagtgca cggcccagcc tggctgaagc tgtaggtcag gggaaggact agaggttagt10861
ggagaccccg tgccacaaaa caccacaaca aaacagcata ttgacacctg ggatagacta10921
ggagatcttc tgctctgcac aaccagccac acggcacagt gcgccgacaa tggtggctgg10981
tggtgcgaga acacaggatc t 11002
<210> 16
<211> 3424
<212> PRT
<213> 人工序列
<220>
<223> 合成的构建体
<400> 16
Met Ser Lys Lys Pro Gly Gly Pro Gly Lys Ser Arg Ala Val Asn Met
1 5 10 15
Leu Lys Arg Gly Met Pro Arg Val Leu Ser Leu Ile Gly Leu Lys Arg
20 25 30
Ala Met Leu Ser Leu Ile Asp Gly Lys Gly Pro Ile Arg Phe Val Leu
35 40 45
Ala Leu Leu Ala Phe Phe Arg Phe Thr Ala Ile Ala Pro Thr Arg Ala
50 55 60
Val Leu Asp Arg Trp Arg Gly Val Asn Lys Gln Thr Ala Met Lys His
65 70 75 80
Leu Leu Ser Phe Lys Lys Glu Leu Gly Thr Leu Thr Ser Ala Ile Asn
85 90 95
Arg Arg Ser Ser Lys Gln Lys Lys Arg Gly Gly Lys Thr Gly Ile Leu
100 105 110
Cys Leu Met Met Met Leu Pro Ala Thr Leu Ala Phe His Leu Thr Ser
115 120 125
Arg Asp Gly Glu Pro Arg Met Ile Val Gly Lys Asn Glu Arg Gly Lys
130 135 140
Ser Leu Leu Phe Lys Thr Ala Ser Gly Ile Asn Met Cys Thr Leu Ile
145 150 155 160
Ala Met Asp Leu Gly Glu Met Cys Asp Asp Thr Val Thr Tyr Lys Cys
165 170 175
Pro His Ile Thr Glu Val Glu Pro Glu Asp Ile Asp Cys Trp Cys Asn
180 185 190
Leu Thr Ser Thr Trp Val Thr Tyr Gly Thr Cys Asn Gln Ala Gly Glu
195 200 205
His Arg Arg Asp Lys Arg Ser Val Ala Leu Ala Pro His Val Gly Met
210 215 220
Gly Leu Asp Thr Arg Thr Gln Thr Trp Met Ser Ala Glu Gly Ala Trp
225 230 235 240
Arg Gln Val Glu Lys Val Glu Thr Trp Ala Leu Arg His Pro Gly Phe
245 250 255
Thr Ile Leu Ala Leu Phe Leu Ala His Tyr Ile Gly Thr Ser Leu Thr
260 265 270
Gln Lys Val Val Ile Phe Ile Leu Leu Met Leu Val Thr Pro Ser Met
275 280 285
Thr Met Arg Cys Val Gly Val Gly Asn Arg Asp Phe Val Glu Gly Leu
290 295 300
Ser Gly Ala Thr Trp Val Asp Val Val Leu Glu His Gly Gly Cys Val
305 310 315 320
Thr Thr Met Ala Lys Asn Lys Pro Thr Leu Asp Ile Glu Leu Gln Lys
325 330 335
Thr Glu Ala Thr Gln Leu Ala Thr Leu Arg Lys Leu Cys Ile Glu Gly
340 345 350
Lys Ile Thr Asn Ile Thr Thr Asp Ser Arg Cys Pro Thr Gln Gly Glu
355 360 365
Ala Ile Leu Pro Glu Glu Gln Asp Gln Asn Tyr Val Cys Lys His Thr
370 375 380
Tyr Val Asp Arg Gly Trp Gly Asn Gly Cys Gly Leu Phe Gly Lys Gly
385 390 395 400
Ser Leu Val Thr Cys Ala Lys Phe Gln Cys Leu Glu Ser Ile Glu Gly
405 410 415
Lys Val Val Gln His Glu Asn Leu Lys Tyr Thr Val Ile Ile Thr Val
420 425 430
His Thr Gly Asp Gln His Gln Val Gly Asn Glu Thr Gln Gly Val Thr
435 440 445
Ala Glu Ile Thr Pro Gln Ala Ser Thr Ala Glu Ala Ile Leu Pro Glu
450 455 460
Tyr Gly Thr Leu Gly Leu Glu Cys Ser Pro Arg Thr Gly Leu Asp Phe
465 470 475 480
Asn Glu Met Ile Ser Leu Thr Met Lys Asn Lys Ala Trp Met Val His
485 490 495
Arg Gln Trp Phe Phe Asp Leu Pro Leu Pro Trp Thr Ser Gly Ala Thr
500 505 510
Ala Glu Thr Pro Thr Trp Asn Arg Lys Glu Leu Leu Val Thr Phe Lys
515 520 525
Asn Ala His Ala Lys Lys Gln Glu Val Val Val Leu Gly Ser Gln Glu
530 535 540
Gly Ala Met His Thr Ala Leu Thr Gly Ala Thr Glu Ile Gln Thr Ser
545 550 555 560
Gly Gly Thr Ser Ile Phe Ala Gly His Leu Lys Cys Arg Leu Lys Met
565 570 575
Asp Lys Leu Glu Leu Lys Gly Met Ser Tyr Ala Met Cys Leu Ser Ser
580 585 590
Phe Val Leu Lys Lys Glu Val Ser Glu Thr Gln His Gly Thr Ile Leu
595 600 605
Ile Lys Val Glu Tyr Lys Gly Glu Asp Ala Pro Cys Lys Ile Pro Phe
610 615 620
Ser Thr Glu Asp Gly Gln Gly Lys Ala Leu Asn Gly Arg Leu Ile Thr
625 630 635 640
Ala Asn Pro Val Val Thr Lys Lys Glu Glu Pro Val Asn Ile Glu Ala
645 650 655
Glu Pro Pro Phe Gly Glu Ser Asn Ile Val Ile Gly Ile Gly Asp Lys
660 665 670
Ala Leu Lys Ile Asn Trp Tyr Lys Lys Gly Ser Ser Ile Gly Lys Met
675 680 685
Phe Glu Ala Thr Ala Arg Gly Ala Arg Arg Met Ala Ile Leu Gly Asp
690 695 700
Thr Ala Trp Asp Phe Gly Ser Val Gly Gly Val Leu Asn Ser Leu Gly
705 710 715 720
Lys Met Val His Gln Ile Phe Gly Ser Ala Tyr Thr Ala Leu Phe Gly
725 730 735
Gly Val Ser Trp Met Met Lys Ile Gly Ile Gly Val Leu Leu Thr Trp
740 745 750
Ile Gly Leu Asn Ser Lys Asn Thr Ser Met Ser Phe Ser Cys Ile Ala
755 760 765
Ile Gly Ile Ile Thr Leu Tyr Leu Gly Ala Val Val Gln Ala Asp Ser
770 775 780
Gly Cys Ala Ile Asp Ile Ser Arg Gln Glu Leu Arg Cys Gly Ser Gly
785 790 795 800
Val Phe Ile His Asn Asp Val Glu Ala Trp Met Asp Arg Tyr Lys Tyr
805 810 815
Tyr Pro Glu Thr Pro Gln Gly Leu Ala Lys Ile Ile Gln Lys Ala His
820 825 830
Lys Glu Gly Val Cys Gly Leu Arg Ser Val Ser Arg Leu Glu His Gln
835 840 845
Met Trp Glu Ala Val Lys Asp Glu Leu Asn Thr Leu Leu Lys Glu Asn
850 855 860
Gly Val Asp Leu Ser Val Val Val Glu Lys Gln Glu Gly Met Tyr Lys
865 870 875 880
Ser Ala Pro Lys Arg Leu Thr Ala Thr Thr Glu Lys Leu Glu Ile Gly
885 890 895
Trp Lys Ala Trp Gly Lys Ser Ile Leu Phe Ala Pro Glu Leu Ala Asn
900 905 910
Asn Thr Phe Val Val Asp Gly Pro Glu Thr Lys Glu Cys Pro Thr Gln
915 920 925
Asn Arg Ala Trp Asn Ser Leu Glu Val Glu Asp Phe Gly Phe Gly Leu
930 935 940
Thr Ser Thr Arg Met Phe Leu Lys Val Arg Glu Ser Asn Thr Thr Glu
945 950 955 960
Cys Asp Ser Lys Ile Ile Gly Thr Ala Val Lys Asn Asn Leu Ala Ile
965 970 975
His Ser Asp Leu Ser Tyr Trp Ile Glu Ser Arg Leu Asn Asp Thr Trp
980 985 990
Lys Leu Glu Arg Ala Val Leu Gly Glu Val Lys Ser Cys Thr Trp Pro
995 1000 1005
Glu Thr His Thr Leu Trp Gly Asp Gly Ile Leu Glu Ser Asp Leu
1010 1015 1020
Ile Ile Pro Val Thr Leu Ala Gly Pro Arg Ser Asn His Asn Arg
1025 1030 1035
Arg Pro Gly Tyr Lys Thr Gln Asn Gln Gly Pro Trp Asp Glu Gly
1040 1045 1050
Arg Val Glu Ile Asp Phe Asp Tyr Cys Pro Gly Thr Thr Val Thr
1055 1060 1065
Leu Ser Glu Ser Cys Gly His Arg Gly Pro Ala Thr Arg Thr Thr
1070 1075 1080
Thr Glu Ser Gly Lys Leu Ile Thr Asp Trp Cys Cys Arg Ser Cys
1085 1090 1095
Thr Leu Pro Pro Leu Arg Tyr Gln Thr Asp Ser Gly Cys Trp Tyr
1100 1105 1110
Gly Met Glu Ile Arg Pro Gln Arg His Asp Glu Lys Thr Leu Val
1115 1120 1125
Gln Ser Gln Val Asn Ala Tyr Asn Ala Asp Met Ile Asp Pro Phe
1130 1135 1140
Gln Leu Gly Leu Leu Val Val Phe Leu Ala Thr Gln Glu Val Leu
1145 1150 1155
Arg Lys Arg Trp Thr Ala Lys Ile Ser Met Pro Ala Ile Leu Ile
1160 1165 1170
Ala Leu Leu Val Leu Val Phe Gly Gly Ile Thr Tyr Thr Asp Val
1175 1180 1185
Leu Arg Tyr Val Ile Leu Val Gly Ala Ala Phe Ala Glu Ser Asn
1190 1195 1200
Ser Gly Gly Asp Val Val His Leu Ala Leu Met Ala Thr Phe Lys
1205 1210 1215
Ile Gln Pro Val Phe Met Val Ala Ser Phe Leu Lys Ala Arg Trp
1220 1225 1230
Thr Asn Gln Glu Asn Ile Leu Leu Met Leu Ala Ala Val Phe Phe
1235 1240 1245
Gln Met Ala Tyr Tyr Asp Ala Arg Gln Ile Leu Leu Trp Glu Ile
1250 1255 1260
Pro Asp Val Leu Asn Ser Leu Ala Val Ala Trp Met Ile Leu Arg
1265 1270 1275
Ala Ile Thr Phe Thr Thr Thr Ser Asn Val Val Val Pro Leu Leu
1280 1285 1290
Ala Leu Leu Thr Pro Gly Leu Arg Cys Leu Asn Leu Asp Val Tyr
1295 1300 1305
Arg Ile Leu Leu Leu Met Val Gly Ile Gly Ser Leu Ile Arg Glu
1310 1315 1320
Lys Arg Ser Ala Ala Ala Lys Lys Lys Gly Ala Ser Leu Leu Cys
1325 1330 1335
Leu Ala Leu Ala Ser Thr Gly Leu Phe Asn Pro Met Ile Leu Ala
1340 1345 1350
Ala Gly Leu Ile Ala Cys Asp Pro Asn Arg Lys Arg Gly Trp Pro
1355 1360 1365
Ala Thr Glu Val Met Thr Ala Val Gly Leu Met Phe Ala Ile Val
1370 1375 1380
Gly Gly Leu Ala Glu Leu Asp Ile Asp Ser Met Ala Ile Pro Met
1385 1390 1395
Thr Ile Ala Gly Leu Met Phe Ala Ala Phe Val Ile Ser Gly Lys
1400 1405 1410
Ser Thr Asp Met Trp Ile Glu Arg Thr Ala Asp Ile Ser Trp Glu
1415 1420 1425
Ser Asp Ala Glu Ile Thr Gly Ser Ser Glu Arg Val Asp Val Arg
1430 1435 1440
Leu Asp Asp Asp Gly Asn Phe Gln Leu Met Asn Asp Pro Gly Ala
1445 1450 1455
Pro Trp Lys Ile Trp Met Leu Arg Met Val Cys Leu Ala Ile Ser
1460 1465 1470
Ala Tyr Thr Pro Trp Ala Ile Leu Pro Ser Val Val Gly Phe Trp
1475 1480 1485
Ile Thr Leu Gln Tyr Thr Lys Arg Gly Gly Val Leu Trp Asp Thr
1490 1495 1500
Pro Ser Pro Lys Glu Tyr Lys Lys Gly Asp Thr Thr Thr Gly Val
1505 1510 1515
Tyr Arg Ile Met Thr Arg Gly Leu Leu Gly Ser Tyr Gln Ala Gly
1520 1525 1530
Ala Gly Val Met Val Glu Gly Val Phe His Thr Leu Trp His Thr
1535 1540 1545
Thr Lys Gly Ala Ala Leu Met Ser Gly Glu Gly Arg Leu Asp Pro
1550 1555 1560
Tyr Trp Gly Ser Val Lys Glu Asp Arg Leu Cys Tyr Gly Gly Pro
1565 1570 1575
Trp Lys Leu Gln His Lys Trp Asn Gly Gln Asp Glu Val Gln Met
1580 1585 1590
Ile Val Val Glu Pro Gly Arg Asn Val Lys Asn Val Gln Thr Lys
1595 1600 1605
Pro Gly Val Phe Lys Thr Pro Glu Gly Glu Ile Gly Ala Val Thr
1610 1615 1620
Leu Asp Phe Pro Thr Gly Thr Ser Gly Ser Pro Ile Val Asp Lys
1625 1630 1635
Asn Gly Asp Val Ile Gly Leu Tyr Gly Asn Gly Val Ile Met Pro
1640 1645 1650
Asn Gly Ser Tyr Ile Ser Ala Ile Val Gln Gly Glu Arg Met Asp
1655 1660 1665
Glu Pro Ile Pro Ala Gly Phe Glu Pro Glu Met Leu Arg Lys Lys
1670 1675 1680
Gln Ile Thr Val Leu Asp Leu His Pro Gly Ala Gly Lys Thr Arg
1685 1690 1695
Arg Ile Leu Pro Gln Ile Ile Lys Glu Ala Ile Asn Arg Arg Leu
1700 1705 1710
Arg Thr Ala Val Leu Ala Pro Thr Arg Val Val Ala Ala Glu Met
1715 1720 1725
Ala Glu Ala Leu Arg Gly Leu Pro Ile Arg Tyr Gln Thr Ser Ala
1730 1735 1740
Val Pro Arg Glu His Asn Gly Asn Glu Ile Val Asp Val Met Cys
1745 1750 1755
His Ala Thr Leu Thr His Arg Leu Met Ser Pro His Arg Val Pro
1760 1765 1770
Asn Tyr Asn Leu Phe Val Met Asp Glu Ala His Phe Thr Asp Pro
1775 1780 1785
Ala Ser Ile Ala Ala Arg Gly Tyr Ile Ser Thr Lys Val Glu Leu
1790 1795 1800
Gly Glu Ala Ala Ala Ile Phe Met Thr Ala Thr Pro Pro Gly Thr
1805 1810 1815
Ser Asp Pro Phe Pro Glu Ser Asn Ser Pro Ile Ser Asp Leu Gln
1820 1825 1830
Thr Glu Ile Pro Asp Arg Ala Trp Asn Ser Gly Tyr Glu Trp Ile
1835 1840 1845
Thr Glu Tyr Thr Gly Lys Thr Val Trp Phe Val Pro Ser Val Lys
1850 1855 1860
Met Gly Asn Glu Ile Ala Leu Cys Leu Gln Arg Ala Gly Lys Lys
1865 1870 1875
Val Val Gln Leu Asn Arg Lys Ser Tyr Glu Thr Glu Tyr Pro Lys
1880 1885 1890
Cys Lys Asn Asp Asp Trp Asp Phe Val Ile Thr Thr Asp Ile Ser
1895 1900 1905
Glu Met Gly Ala Asn Phe Lys Ala Ser Arg Val Ile Asp Ser Arg
1910 1915 1920
Lys Ser Val Lys Pro Thr Ile Ile Thr Glu Gly Glu Gly Arg Val
1925 1930 1935
Ile Leu Gly Glu Pro Ser Ala Val Thr Ala Ala Ser Ala Ala Gln
1940 1945 1950
Arg Arg Gly Arg Ile Gly Arg Asn Pro Ser Gln Val Gly Asp Glu
1955 1960 1965
Tyr Cys Tyr Gly Gly His Thr Asn Glu Asp Asp Ser Asn Phe Ala
1970 1975 1980
His Trp Thr Glu Ala Arg Ile Met Leu Asp Asn Ile Asn Met Pro
1985 1990 1995
Asn Gly Leu Ile Ala Gln Phe Tyr Gln Pro Glu Arg Glu Lys Val
2000 2005 2010
Tyr Thr Met Asp Gly Glu Tyr Arg Leu Arg Gly Glu Glu Arg Lys
2015 2020 2025
Asn Phe Leu Glu Leu Leu Arg Thr Ala Asp Leu Pro Val Trp Leu
2030 2035 2040
Ala Tyr Lys Val Ala Ala Ala Gly Val Ser Tyr His Asp Arg Arg
2045 2050 2055
Trp Cys Phe Asp Gly Pro Arg Thr Asn Thr Ile Leu Glu Asp Asn
2060 2065 2070
Asn Glu Val Glu Val Ile Thr Lys Leu Gly Glu Arg Lys Ile Leu
2075 2080 2085
Arg Pro Arg Trp Ile Asp Ala Arg Val Tyr Ser Asp His Gln Ala
2090 2095 2100
Leu Lys Ala Phe Lys Asp Phe Ala Ser Gly Lys Arg Ser Gln Ile
2105 2110 2115
Gly Leu Ile Glu Val Leu Gly Lys Met Pro Glu His Phe Met Gly
2120 2125 2130
Lys Thr Trp Glu Ala Leu Asp Thr Met Tyr Val Val Ala Thr Ala
2135 2140 2145
Glu Lys Gly Gly Arg Ala His Arg Met Ala Leu Glu Glu Leu Pro
2150 2155 2160
Asp Ala Leu Gln Thr Ile Ala Leu Ile Ala Leu Leu Ser Val Met
2165 2170 2175
Thr Met Gly Val Phe Phe Leu Leu Met Gln Arg Lys Gly Ile Gly
2180 2185 2190
Lys Ile Gly Leu Gly Gly Ala Val Leu Gly Val Ala Thr Phe Phe
2195 2200 2205
Cys Trp Met Ala Glu Val Pro Gly Thr Lys Ile Ala Gly Met Leu
2210 2215 2220
Leu Leu Ser Leu Leu Leu Met Ile Val Leu Ile Pro Glu Pro Glu
2225 2230 2235
Lys Gln Arg Ser Gln Thr Asp Asn Gln Leu Ala Val Phe Leu Ile
2240 2245 2250
Cys Val Met Thr Leu Val Ser Ala Val Ala Ala Asn Glu Met Gly
2255 2260 2265
Trp Leu Asp Lys Thr Lys Ser Asp Ile Ser Ser Leu Phe Gly Gln
2270 2275 2280
Arg Ile Glu Val Lys Glu Asn Phe Ser Met Gly Glu Phe Leu Leu
2285 2290 2295
Asp Leu Arg Pro Ala Thr Ala Trp Ser Leu Tyr Ala Val Thr Thr
2300 2305 2310
Ala Val Leu Thr Pro Leu Leu Lys His Leu Ile Thr Ser Asp Tyr
2315 2320 2325
Ile Asn Thr Ser Leu Thr Ser Ile Asn Val Gln Ala Ser Ala Leu
2330 2335 2340
Phe Thr Leu Ala Arg Gly Phe Pro Phe Val Asp Val Gly Val Ser
2345 2350 2355
Ala Leu Leu Leu Ala Ala Gly Cys Trp Gly Gln Val Thr Leu Thr
2360 2365 2370
Val Thr Val Thr Ala Ala Thr Leu Leu Phe Cys His Tyr Ala Tyr
2375 2380 2385
Met Val Pro Gly Trp Gln Ala Glu Ala Met Arg Ser Ala Gln Arg
2390 2395 2400
Arg Thr Ala Ala Gly Ile Met Lys Asn Ala Val Val Asp Gly Ile
2405 2410 2415
Val Ala Thr Asp Val Pro Glu Leu Glu Arg Thr Thr Pro Ile Met
2420 2425 2430
Gln Lys Lys Val Gly Gln Ile Met Leu Ile Leu Val Ser Leu Ala
2435 2440 2445
Ala Val Val Val Asn Pro Ser Val Lys Thr Val Arg Glu Ala Gly
2450 2455 2460
Ile Leu Ile Thr Ala Ala Ala Val Thr Leu Trp Glu Asn Gly Ala
2465 2470 2475
Ser Ser Val Trp Asn Ala Thr Thr Ala Ile Gly Leu Cys His Ile
2480 2485 2490
Met Arg Gly Gly Trp Leu Ser Cys Leu Ser Ile Thr Trp Thr Leu
2495 2500 2505
Ile Lys Asn Met Glu Lys Pro Gly Leu Lys Arg Gly Gly Ala Lys
2510 2515 2520
Gly Arg Thr Leu Gly Glu Val Trp Lys Glu Arg Leu Asn Gln Met
2525 2530 2535
Thr Lys Glu Glu Phe Thr Arg Tyr Arg Lys Glu Ala Ile Ile Glu
2540 2545 2550
Val Asp Arg Ser Ala Ala Lys His Ala Arg Lys Glu Gly Asn Val
2555 2560 2565
Thr Gly Gly His Pro Val Ser Arg Gly Thr Ala Lys Leu Arg Trp
2570 2575 2580
Leu Val Glu Arg Arg Phe Leu Glu Pro Val Gly Lys Val Ile Asp
2585 2590 2595
Leu Gly Cys Gly Arg Gly Gly Trp Cys Tyr Tyr Met Ala Thr Gln
2600 2605 2610
Lys Arg Val Gln Glu Val Arg Gly Tyr Thr Lys Gly Gly Pro Gly
2615 2620 2625
His Glu Glu Pro Gln Leu Val Gln Ser Tyr Gly Trp Asn Ile Val
2630 2635 2640
Thr Met Lys Ser Gly Val Asp Val Phe Tyr Arg Pro Ser Glu Cys
2645 2650 2655
Cys Asp Thr Leu Leu Cys Asp Ile Gly Glu Ser Ser Ser Ser Ala
2660 2665 2670
Glu Val Glu Glu His Arg Thr Ile Arg Val Leu Glu Met Val Glu
2675 2680 2685
Asp Trp Leu His Arg Gly Pro Arg Glu Phe Cys Val Lys Val Leu
2690 2695 2700
Cys Pro Tyr Met Pro Lys Val Ile Glu Lys Met Glu Leu Leu Gln
2705 2710 2715
Arg Arg Tyr Gly Gly Gly Leu Val Arg Asn Pro Leu Ser Arg Asn
2720 2725 2730
Ser Thr His Glu Met Tyr Trp Val Ser Arg Ala Ser Gly Asn Val
2735 2740 2745
Val His Ser Val Asn Met Thr Ser Gln Val Leu Leu Gly Arg Met
2750 2755 2760
Glu Lys Arg Thr Trp Lys Gly Pro Gln Tyr Glu Glu Asp Val Asn
2765 2770 2775
Leu Gly Ser Gly Thr Arg Ala Val Gly Lys Pro Leu Leu Asn Ser
2780 2785 2790
Asp Thr Ser Lys Ile Lys Asn Arg Ile Glu Arg Leu Arg Arg Glu
2795 2800 2805
Tyr Ser Ser Thr Trp His His Asp Glu Asn His Pro Tyr Arg Thr
2810 2815 2820
Trp Asn Tyr His Gly Ser Tyr Asp Val Lys Pro Thr Gly Ser Ala
2825 2830 2835
Ser Ser Leu Val Asn Gly Val Val Arg Leu Leu Ser Lys Pro Trp
2840 2845 2850
Asp Thr Ile Thr Asn Val Thr Thr Met Ala Met Thr Asp Thr Thr
2855 2860 2865
Pro Phe Gly Gln Gln Arg Val Phe Lys Glu Lys Val Asp Thr Lys
2870 2875 2880
Ala Pro Glu Pro Pro Glu Gly Val Lys Tyr Val Leu Asn Glu Thr
2885 2890 2895
Thr Asn Trp Leu Trp Ala Phe Leu Ala Arg Glu Lys Arg Pro Arg
2900 2905 2910
Met Cys Ser Arg Glu Glu Phe Ile Arg Lys Val Asn Ser Asn Ala
2915 2920 2925
Ala Leu Gly Ala Met Phe Glu Glu Gln Asn Gln Trp Arg Ser Ala
2930 2935 2940
Arg Glu Ala Val Glu Asp Pro Lys Phe Trp Glu Met Val Asp Glu
2945 2950 2955
Glu Arg Glu Ala His Leu Arg Gly Glu Cys His Thr Cys Ile Tyr
2960 2965 2970
Asn Met Met Gly Lys Arg Glu Lys Lys Pro Gly Glu Phe Gly Lys
2975 2980 2985
Ala Lys Gly Ser Arg Ala Ile Trp Phe Met Trp Leu Gly Ala Arg
2990 2995 3000
Phe Leu Glu Phe Glu Ala Leu Gly Phe Leu Asn Glu Asp His Trp
3005 3010 3015
Leu Gly Arg Lys Asn Ser Gly Gly Gly Val Glu Gly Leu Gly Leu
3020 3025 3030
Gln Lys Leu Gly Tyr Ile Leu Arg Glu Val Gly Thr Arg Pro Gly
3035 3040 3045
Gly Lys Ile Tyr Ala Asp Asp Thr Ala Gly Trp Asp Thr Arg Ile
3050 3055 3060
Thr Arg Ala Asp Leu Glu Asn Glu Ala Lys Val Leu Glu Leu Leu
3065 3070 3075
Asp Gly Glu His Arg Arg Leu Ala Arg Ala Ile Ile Glu Leu Thr
3080 3085 3090
Tyr Arg His Lys Val Val Lys Val Met Arg Pro Ala Ala Asp Gly
3095 3100 3105
Arg Thr Val Met Asp Val Ile Ser Arg Glu Asp Gln Arg Gly Ser
3110 3115 3120
Gly Gln Val Val Thr Tyr Ala Leu Asn Thr Phe Thr Asn Leu Ala
3125 3130 3135
Val Gln Leu Val Arg Met Met Glu Gly Glu Gly Val Ile Gly Pro
3140 3145 3150
Asp Asp Val Glu Lys Leu Thr Lys Gly Lys Gly Pro Lys Val Arg
3155 3160 3165
Thr Trp Leu Phe Glu Asn Gly Glu Glu Arg Leu Ser Arg Met Ala
3170 3175 3180
Val Ser Gly Asp Asp Cys Val Val Lys Pro Leu Asp Asp Arg Phe
3185 3190 3195
Ala Thr Ser Leu His Phe Leu Asn Ala Met Ser Lys Val Arg Lys
3200 3205 3210
Asp Ile Gln Glu Trp Lys Pro Ser Thr Gly Trp Tyr Asp Trp Gln
3215 3220 3225
Gln Val Pro Phe Cys Ser Asn His Phe Thr Glu Leu Ile Met Lys
3230 3235 3240
Asp Gly Arg Thr Leu Val Val Pro Cys Arg Gly Gln Asp Glu Leu
3245 3250 3255
Val Gly Arg Ala Arg Ile Ser Pro Gly Ala Gly Trp Asn Val Arg
3260 3265 3270
Asp Thr Ala Cys Leu Ala Lys Ser Tyr Ala Gln Met Trp Leu Leu
3275 3280 3285
Leu Tyr Phe His Arg Arg Asp Leu Arg Leu Met Ala Asn Ala Ile
3290 3295 3300
Cys Ser Ala Val Pro Val Asn Trp Val Pro Thr Gly Arg Thr Thr
3305 3310 3315
Trp Ser Ile His Ala Gly Gly Glu Trp Met Thr Thr Glu Asp Met
3320 3325 3330
Leu Glu Val Trp Asn Arg Val Trp Ile Glu Glu Asn Glu Trp Met
3335 3340 3345
Glu Asp Lys Thr Pro Val Glu Lys Trp Ser Asp Val Pro Tyr Ser
3350 3355 3360
Gly Lys Arg Glu Asp Ile Trp Cys Gly Ser Leu Ile Gly Thr Arg
3365 3370 3375
Ala Arg Ala Thr Trp Ala Glu Asn Ile Gln Val Ala Ile Asn Gln
3380 3385 3390
Val Arg Ala Ile Ile Gly Asp Glu Lys Tyr Val Asp Tyr Met Ser
3395 3400 3405
Ser Leu Lys Arg Tyr Glu Asp Thr Thr Leu Val Glu Asp Thr Val
3410 3415 3420
Leu
<210> 17
<211> 11002
<212> DNA
<213> 人工序列
<220>
<223> 具有 E345 His 到 Leu突变的WN/DEN3嵌合体(CE345)
<220>
<221> CDS
<222> (97)..(10371)
<400> 17
agtagttcgc ctgtgtgagc tgacaaactt agtagtgttt gtgaggatta acaacaatta 60
acacagtgcg agctgtttct tagcacgaag atctcg atg tct aag aaa cca gga 114
Met Ser Lys Lys Pro Gly
1 5
ggg ccc ggc aag agc cgg gct gtc aat atg cta aaa cgc gga atg ccc 162
Gly Pro Gly Lys Ser Arg Ala Val Asn Met Leu Lys Arg Gly Met Pro
10 15 20
cgc gtg ttg tcc ttg att gga ctg aag agg gct atg ttg agc ctg atc 210
Arg Val Leu Ser Leu Ile Gly Leu Lys Arg Ala Met Leu Ser Leu Ile
25 30 35
gac ggc aag ggg cca ata cga ttt gtg ttg gct ctc ttg gcg ttc ttc 258
Asp Gly Lys Gly Pro Ile Arg Phe Val Leu Ala Leu Leu Ala Phe Phe
40 45 50
agg ttc aca gca att gct ccg acc cga gca gtg ctg gat cga tgg aga 306
Arg Phe Thr Ala Ile Ala Pro Thr Arg Ala Val Leu Asp Arg Trp Arg
55 60 65 70
ggt gtg aac aaa caa aca gcg atg aaa cac ctt ctg agt ttt aag aag 354
Gly Val Asn Lys Gln Thr Ala Met Lys His Leu Leu Ser Phe Lys Lys
75 80 85
gaa cta ggg acc ttg acc agt gct atc aat cgg cgg agt tcg aaa caa 402
Glu Leu Gly Thr Leu Thr Ser Ala Ile Asn Arg Arg Ser Ser Lys Gln
90 95 100
aag aaa aga gga gga aag acc gga att gca gtc atg att ggc ctg atc 450
Lys Lys Arg Gly Gly Lys Thr Gly Ile Ala Val Met Ile Gly Leu Ile
105 110 115
gcc agc gta gga gct ttc cac tta act tca cga gat gga gag ccg cgc 498
Ala Ser Val Gly Ala Phe His Leu Thr Ser Arg Asp Gly Glu Pro Arg
120 125 130
atg att gtg ggg aag aat gaa aga gga aaa tcc cta ctt ttc aag aca 546
Met Ile Val Gly Lys Asn Glu Arg Gly Lys Ser Leu Leu Phe Lys Thr
135 140 145 150
gcc tct gga atc aac atg tgc aca ctc ata gcc atg gat ctg gga gag 594
Ala Ser Gly Ile Asn Met Cys Thr Leu Ile Ala Met Asp Leu Gly Glu
155 160 165
atg tgt gat gac acg gtc act tac aaa tgc ccc cac att acc gaa gtg 642
Met Cys Asp Asp Thr Val Thr Tyr Lys Cys Pro His Ile Thr Glu Val
170 175 180
gag cct gaa gac att gac tgc tgg tgc aac ctt aca tcg aca tgg gtg 690
Glu Pro Glu Asp Ile Asp Cys Trp Cys Asn Leu Thr Ser Thr Trp Val
185 190 195
act tat gga aca tgc aat caa gct gga gag cat aga cgc gat aag aga 738
Thr Tyr Gly Thr Cys Asn Gln Ala Gly Glu His Arg Arg Asp Lys Arg
200 205 210
tca gtg gcg tta gct ccc cat gtt ggc atg gga ctg gac aca cgc act 786
Ser Val Ala Leu Ala Pro His Val Gly Met Gly Leu Asp Thr Arg Thr
215 220 225 230
caa acc tgg atg tcg gct gaa gga gct tgg aga caa gtc gag aag gta 834
Gln Thr Trp Met Ser Ala Glu Gly Ala Trp Arg Gln Val Glu Lys Val
235 240 245
gag aca tgg gcc ctt agg cac cca ggg ttt acc ata cta gcc cta ttt 882
Glu Thr Trp Ala Leu Arg His Pro Gly Phe Thr Ile Leu Ala Leu Phe
250 255 260
ctt gcc cat tac ata ggc act tcc ttg acc cag aaa gtg gtt att ttt 930
Leu Ala His Tyr Ile Gly Thr Ser Leu Thr Gln Lys Val Val Ile Phe
265 270 275
ata cta tta atg ctg gtt acc cca tcc atg aca atg aga tgt gta gga 978
Ile Leu Leu Met Leu Val Thr Pro Ser Met Thr Met Arg Cys Val Gly
280 285 290
gta gga aac aga gat ttt gtg gaa ggc cta tcg gga gct acg tgg gtt 1026
Val Gly Asn Arg Asp Phe Val Glu Gly Leu Ser Gly Ala Thr Trp Val
295 300 305 310
gac gtg gtg ctc gag cac ggt ggg tgt gtg act acc atg gct aag aac 1074
Asp Val Val Leu Glu His Gly Gly Cys Val Thr Thr Met Ala Lys Asn
315 320 325
aag ccc acg ctg gac ata gag ctt cag aag acc gag gcc acc caa ctg 1122
Lys Pro Thr Leu Asp Ile Glu Leu Gln Lys Thr Glu Ala Thr Gln Leu
330 335 340
gcg acc cta agg aag cta tgc att gag gga aaa att acc aac ata aca 1170
Ala Thr Leu Arg Lys Leu Cys Ile Glu Gly Lys Ile Thr Asn Ile Thr
345 350 355
acc gac tca aga tgt ccc acc caa ggg gaa gcg att tta cct gag gag 1218
Thr Asp Ser Arg Cys Pro Thr Gln Gly Glu Ala Ile Leu Pro Glu Glu
360 365 370
cag gac cag aac tac gtg tgt aag cat aca tac gtg gac aga ggc tgg 1266
Gln Asp Gln Asn Tyr Val Cys Lys His Thr Tyr Val Asp Arg Gly Trp
375 380 385 390
gga aac ggt tgt ggt ttg ttt ggc aag gga agc ttg gtg aca tgc gcg 1314
Gly Asn Gly Cys Gly Leu Phe Gly Lys Gly Ser Leu Val Thr Cys Ala
395 400 405
aaa ttt caa tgt tta gaa tca ata gag gga aaa gtg gtg caa cat gag 1362
Lys Phe Gln Cys Leu Glu Ser Ile Glu Gly Lys Val Val Gln His Glu
410 415 420
aac ctc aaa tac acc gtc atc atc aca gtg cac aca gga gac caa cac 1410
Asn Leu Lys Tyr Thr Val Ile Ile Thr Val His Thr Gly Asp Gln His
425 430 435
cag gtg gga aat gaa acg cag gga gtc acg gct gag ata aca ccc cag 1458
Gln Val Gly Asn Glu Thr Gln Gly Val Thr Ala Glu Ile Thr Pro Gln
440 445 450
gca tca acc gct gaa gcc att tta cct gaa tat gga acc ctc ggg cta 1506
Ala Ser Thr Ala Glu Ala Ile Leu Pro Glu Tyr Gly Thr Leu Gly Leu
455 460 465 470
gaa tgc tca cca cgg aca ggt ttg gat ttc aat gaa atg atc tca ttg 1554
Glu Cys Ser Pro Arg Thr Gly Leu Asp Phe Asn Glu Met Ile Ser Leu
475 480 485
aca atg aag aac aaa gca tgg atg gta cat aga caa tgg ttc ttt gac 1602
Thr Met Lys Asn Lys Ala Trp Met Val His Arg Gln Trp Phe Phe Asp
490 495 500
tta ccc cta cca tgg aca tca gga gct aca gca gaa aca cca act tgg 1650
Leu Pro Leu Pro Trp Thr Ser Gly Ala Thr Ala Glu Thr Pro Thr Trp
505 510 515
aac agg aaa gag ctt ctt gtg aca ttt aaa aat gca cat gca aaa aag 1698
Asn Arg Lys Glu Leu Leu Val Thr Phe Lys Asn Ala His Ala Lys Lys
520 525 530
caa gaa gta gtt gtt ctt gga tca caa gag gga gca atg cat aca gca 1746
Gln Glu Val Val Val Leu Gly Ser Gln Glu Gly Ala Met His Thr Ala
535 540 545 550
ctg aca gga gct aca gag atc caa acc tca gga ggc aca agt atc ttt 1794
Leu Thr Gly Ala Thr Glu Ile Gln Thr Ser Gly Gly Thr Ser Ile Phe
555 560 565
gcg ggg cac tta aaa tgt aga ctc aag atg gac aaa ttg gaa ctc aag 1842
Ala Gly His Leu Lys Cys Arg Leu Lys Met Asp Lys Leu Glu Leu Lys
570 575 580
ggg atg agc tat gca atg tgc ttg agt agc ttt gtg ttg aag aaa gaa 1890
Gly Met Ser Tyr Ala Met Cys Leu Ser Ser Phe Val Leu Lys Lys Glu
585 590 595
gtc tcc gaa acg cag cat ggg aca ata ctc att aag gtt gag tac aaa 1938
Val Ser Glu Thr Gln His Gly Thr Ile Leu Ile Lys Val Glu Tyr Lys
600 605 610
ggg gaa gat gca ccc tgc aag att cct ttc tcc acg gag gat gga caa 1986
Gly Glu Asp Ala Pro Cys Lys Ile Pro Phe Ser Thr Glu Asp Gly Gln
615 620 625 630
gga aaa gct ctc aat ggc aga ctg atc aca gcc aat cca gtg gtg acc 2034
Gly Lys Ala Leu Asn Gly Arg Leu Ile Thr Ala Asn Pro Val Val Thr
635 640 645
aag aag gag gag cct gtc aac att gag gct gaa cct cct ttt gga gaa 2082
Lys Lys Glu Glu Pro Val Asn Ile Glu Ala Glu Pro Pro Phe Gly Glu
650 655 660
agt aac ata gta att gga att gga gac aaa gcc ctg aaa atc aac tgg 2130
Ser Asn Ile Val Ile Gly Ile Gly Asp Lys Ala Leu Lys Ile Asn Trp
665 670 675
tac aag aag gga agc tcg att ggg aag atg ttc gag gcc act gcc aga 2178
Tyr Lys Lys Gly Ser Ser Ile Gly Lys Met Phe Glu Ala Thr Ala Arg
680 685 690
ggt gca agg cgc atg gcc atc ttg gga gac aca gcc tgg gac ttt gga 2226
Gly Ala Arg Arg Met Ala Ile Leu Gly Asp Thr Ala Trp Asp Phe Gly
695 700 705 710
tca gtg ggt ggt gtt ttg aat tca tta ggg aaa atg gtc cac caa ata 2274
Ser Val Gly Gly Val Leu Asn Ser Leu Gly Lys Met Val His Gln Ile
715 720 725
ttt ggg agt gct tac aca gcc cta ttt ggt gga gtc tcc tgg atg atg 2322
Phe Gly Ser Ala Tyr Thr Ala Leu Phe Gly Gly Val Ser Trp Met Met
730 735 740
aaa att gga ata ggt gtc ctc tta acc tgg ata ggg ttg aac tca aaa 2370
Lys Ile Gly Ile Gly Val Leu Leu Thr Trp Ile Gly Leu Asn Ser Lys
745 750 755
aat act tct atg tca ttt tca tgc atc gcg ata gga atc att aca ctc 2418
Asn Thr Ser Met Ser Phe Ser Cys Ile Ala Ile Gly Ile Ile Thr Leu
760 765 770
tat ctg gga gcc gtg gtg caa gct gac tcc gga tgt gcc ata gac atc 2466
Tyr Leu Gly Ala Val Val Gln Ala Asp Ser Gly Cys Ala Ile Asp Ile
775 780 785 790
agc cgg caa gag ctg aga tgt gga agt gga gtg ttc ata cac aat gat 2514
Ser Arg Gln Glu Leu Arg Cys Gly Ser Gly Val Phe Ile His Asn Asp
795 800 805
gtg gag gct tgg atg gac cgg tac aag tat tac cct gaa acg cca caa 2562
Val Glu Ala Trp Met Asp Arg Tyr Lys Tyr Tyr Pro Glu Thr Pro Gln
810 815 820
ggc cta gcc aag atc att cag aaa gct cat aag gaa gga gtg tgc ggt 2610
Gly Leu Ala Lys Ile Ile Gln Lys Ala His Lys Glu Gly Val Cys Gly
825 830 835
cta cga tca gtt tcc aga ctg gag cat caa atg tgg gaa gca gtg aag 2658
Leu Arg Ser Val Ser Arg Leu Glu His Gln Met Trp Glu Ala Val Lys
840 845 850
gac gag ctg aac act ctt ttg aag gag aat ggt gtg gac ctt agt gtc 2706
Asp Glu Leu Asn Thr Leu Leu Lys Glu Asn Gly Val Asp Leu Ser Val
855 860 865 870
gtg gtt gag aaa cag gag gga atg tac aag tca gca cct aaa cgc ctc 2754
Val Val Glu Lys Gln Glu Gly Met Tyr Lys Ser Ala Pro Lys Arg Leu
875 880 885
acc gcc acc acg gaa aaa ttg gaa att ggc tgg aag gcc tgg gga aag 2802
Thr Ala Thr Thr Glu Lys Leu Glu Ile Gly Trp Lys Ala Trp Gly Lys
890 895 900
agt att tta ttt gca cca gaa ctc gcc aac aac acc ttt gtg gtt gat 2850
Ser Ile Leu Phe Ala Pro Glu Leu Ala Asn Asn Thr Phe Val Val Asp
905 910 915
ggt ccg gag acc aag gaa tgt ccg act cag aat cgc gct tgg aat agc 2898
Gly Pro Glu Thr Lys Glu Cys Pro Thr Gln Asn Arg Ala Trp Asn Ser
920 925 930
tta gaa gtg gag gat ttt gga ttt ggt ctc acc agc act cgg atg ttc 2946
Leu Glu Val Glu Asp Phe Gly Phe Gly Leu Thr Ser Thr Arg Met Phe
935 940 945 950
ctg aag gtc aga gag agc aac aca act gaa tgt gac tcg aag atc att 2994
Leu Lys Val Arg Glu Ser Asn Thr Thr Glu Cys Asp Ser Lys Ile Ile
955 960 965
gga acg gct gtc aag aac aac ttg gcg atc cac agt gac ctg tcc tat 3042
Gly Thr Ala Val Lys Asn Asn Leu Ala Ile His Ser Asp Leu Ser Tyr
970 975 980
tgg att gaa agc agg ctc aat gat acg tgg aag ctt gaa agg gca gtt 3090
Trp Ile Glu Ser Arg Leu Asn Asp Thr Trp Lys Leu Glu Arg Ala Val
985 990 995
ctg ggt gaa gtc aaa tca tgt acg tgg cct gag acg cat acc ttg 3135
Leu Gly Glu Val Lys Ser Cys Thr Trp Pro Glu Thr His Thr Leu
1000 1005 1010
tgg ggc gat gga atc ctt gag agt gac ttg ata ata cca gtc aca 3180
Trp Gly Asp Gly Ile Leu Glu Ser Asp Leu Ile Ile Pro Val Thr
1015 1020 1025
ctg gcg gga cca cga agc aat cac aat cgg aga cct ggg tac aag 3225
Leu Ala Gly Pro Arg Ser Asn His Asn Arg Arg Pro Gly Tyr Lys
1030 1035 1040
aca caa aac cag ggc cca tgg gac gaa ggc cgg gta gag att gac 3270
Thr Gln Asn Gln Gly Pro Trp Asp Glu Gly Arg Val Glu Ile Asp
1045 1050 1055
ttc gat tac tgc cca gga act acg gtc acc ctg agt gag agc tgc 3315
Phe Asp Tyr Cys Pro Gly Thr Thr Val Thr Leu Ser Glu Ser Cys
1060 1065 1070
gga cac cgt gga cct gcc act cgc acc acc aca gag agc gga aag 3360
Gly His Arg Gly Pro Ala Thr Arg Thr Thr Thr Glu Ser Gly Lys
1075 1080 1085
ttg ata aca gat tgg tgc tgc agg agc tgc acc tta cca cca ctg 3405
Leu Ile Thr Asp Trp Cys Cys Arg Ser Cys Thr Leu Pro Pro Leu
1090 1095 1100
cgc tac caa act gac agc ggc tgt tgg tat ggt atg gag atc aga 3450
Arg Tyr Gln Thr Asp Ser Gly Cys Trp Tyr Gly Met Glu Ile Arg
1105 1110 1115
cca cag aga cat gat gaa aag acc ctc gtg cag tca caa gtg aat 3495
Pro Gln Arg His Asp Glu Lys Thr Leu Val Gln Ser Gln Val Asn
1120 1125 1130
gct tat aat gct gat atg att gac cct ttt cag ttg ggc ctt ctg 3540
Ala Tyr Asn Ala Asp Met Ile Asp Pro Phe Gln Leu Gly Leu Leu
1135 1140 1145
gtc gtg ttc ttg gcc acc cag gag gtc ctt cgc aag agg tgg aca 3585
Val Val Phe Leu Ala Thr Gln Glu Val Leu Arg Lys Arg Trp Thr
1150 1155 1160
gcc aag atc agc atg cca gct ata ctg att gct ctg cta gtc ctg 3630
Ala Lys Ile Ser Met Pro Ala Ile Leu Ile Ala Leu Leu Val Leu
1165 1170 1175
gtg ttt ggg ggc att act tac act gat gtg tta cgc tat gtc atc 3675
Val Phe Gly Gly Ile Thr Tyr Thr Asp Val Leu Arg Tyr Val Ile
1180 1185 1190
ttg gtg ggg gca gct ttc gca gaa tct aat tcg gga gga gac gtg 3720
Leu Val Gly Ala Ala Phe Ala Glu Ser Asn Ser Gly Gly Asp Val
1195 1200 1205
gta cac ttg gcg ctc atg gcg acc ttc aag ata caa cca gtg ttt 3765
Val His Leu Ala Leu Met Ala Thr Phe Lys Ile Gln Pro Val Phe
1210 1215 1220
atg gtg gca tcg ttt ctc aaa gcg aga tgg acc aac cag gag aac 3810
Met Val Ala Ser Phe Leu Lys Ala Arg Trp Thr Asn Gln Glu Asn
1225 1230 1235
att ttg ttg atg ttg gcg gct gtt ttc ttt caa atg gct tat tac 3855
Ile Leu Leu Met Leu Ala Ala Val Phe Phe Gln Met Ala Tyr Tyr
1240 1245 1250
gat gcc cgc caa att ctg ctc tgg gag atc cct gat gtg ttg aat 3900
Asp Ala Arg Gln Ile Leu Leu Trp Glu Ile Pro Asp Val Leu Asn
1255 1260 1265
tca ctg gcg gta gct tgg atg ata ctg aga gcc ata aca ttc aca 3945
Ser Leu Ala Val Ala Trp Met Ile Leu Arg Ala Ile Thr Phe Thr
1270 1275 1280
acg aca tca aac gtg gtt gtt ccg ctg cta gcc ctg cta aca ccc 3990
Thr Thr Ser Asn Val Val Val Pro Leu Leu Ala Leu Leu Thr Pro
1285 1290 1295
ggg ctg aga tgc ttg aat ctg gat gtg tac agg ata ctg ctg ttg 4035
Gly Leu Arg Cys Leu Asn Leu Asp Val Tyr Arg Ile Leu Leu Leu
1300 1305 1310
atg gtc gga ata ggc agc ttg atc agg gag aag agg agt gca gct 4080
Met Val Gly Ile Gly Ser Leu Ile Arg Glu Lys Arg Ser Ala Ala
1315 1320 1325
gca aaa aag aaa gga gca agt ctg cta tgc ttg gct cta gcc tca 4125
Ala Lys Lys Lys Gly Ala Ser Leu Leu Cys Leu Ala Leu Ala Ser
1330 1335 1340
aca gga ctt ttc aac ccc atg atc ctt gct gct gga ctg att gca 4170
Thr Gly Leu Phe Asn Pro Met Ile Leu Ala Ala Gly Leu Ile Ala
1345 1350 1355
tgt gat ccc aac cgt aaa cgc gga tgg ccc gca act gaa gtg atg 4215
Cys Asp Pro Asn Arg Lys Arg Gly Trp Pro Ala Thr Glu Val Met
1360 1365 1370
aca gct gtc ggc cta atg ttt gcc atc gtc gga ggg ctg gca gag 4260
Thr Ala Val Gly Leu Met Phe Ala Ile Val Gly Gly Leu Ala Glu
1375 1380 1385
ctt gac att gac tcc atg gcc att cca atg act atc gcg ggg ctc 4305
Leu Asp Ile Asp Ser Met Ala Ile Pro Met Thr Ile Ala Gly Leu
1390 1395 1400
atg ttt gct gct ttc gtg att tct ggg aaa tca aca gat atg tgg 4350
Met Phe Ala Ala Phe Val Ile Ser Gly Lys Ser Thr Asp Met Trp
1405 1410 1415
att gag aga acg gcg gac att tcc tgg gaa agt gat gca gaa att 4395
Ile Glu Arg Thr Ala Asp Ile Ser Trp Glu Ser Asp Ala Glu Ile
1420 1425 1430
aca ggc tcg agc gaa aga gtt gat gtg cgg ctt gat gat gat gga 4440
Thr Gly Ser Ser Glu Arg Val Asp Val Arg Leu Asp Asp Asp Gly
1435 1440 1445
aac ttc cag ctc atg aat gat cca gga gca cct tgg aag ata tgg 4485
Asn Phe Gln Leu Met Asn Asp Pro Gly Ala Pro Trp Lys Ile Trp
1450 1455 1460
atg ctc aga atg gtc tgt ctc gcg att agt gcg tac acc ccc tgg 4530
Met Leu Arg Met Val Cys Leu Ala Ile Ser Ala Tyr Thr Pro Trp
1465 1470 1475
gca atc ttg ccc tca gta gtt gga ttt tgg ata act ctc caa tac 4575
Ala Ile Leu Pro Ser Val Val Gly Phe Trp Ile Thr Leu Gln Tyr
1480 1485 1490
aca aag aga gga ggc gtg ttg tgg gac act ccc tca cca aag gag 4620
Thr Lys Arg Gly Gly Val Leu Trp Asp Thr Pro Ser Pro Lys Glu
1495 1500 1505
tac aaa aag ggg gac acg acc acc ggc gtc tac agg atc atg act 4665
Tyr Lys Lys Gly Asp Thr Thr Thr Gly Val Tyr Arg Ile Met Thr
1510 1515 1520
cgt ggg ctg ctc ggc agt tat caa gca gga gcg ggc gtg atg gtt 4710
Arg Gly Leu Leu Gly Ser Tyr Gln Ala Gly Ala Gly Val Met Val
1525 1530 1535
gaa ggt gtt ttc cac acc ctt tgg cat aca aca aaa gga gcc gct 4755
Glu Gly Val Phe His Thr Leu Trp His Thr Thr Lys Gly Ala Ala
1540 1545 1550
ttg atg agc gga gag ggc cgc ctg gac cca tac tgg ggc agt gtc 4800
Leu Met Ser Gly Glu Gly Arg Leu Asp Pro Tyr Trp Gly Ser Val
1555 1560 1565
aag gag gat cga ctt tgt tac gga gga ccc tgg aaa ttg cag cac 4845
Lys Glu Asp Arg Leu Cys Tyr Gly Gly Pro Trp Lys Leu Gln His
1570 1575 1580
aag tgg aac ggg cag gat gag gtg cag atg att gtg gtg gaa cct 4890
Lys Trp Asn Gly Gln Asp Glu Val Gln Met Ile Val Val Glu Pro
1585 1590 1595
ggc agg aac gtt aag aac gtc cag acg aaa cca ggg gtg ttc aaa 4935
Gly Arg Asn Val Lys Asn Val Gln Thr Lys Pro Gly Val Phe Lys
1600 1605 1610
aca cct gaa gga gaa atc ggg gcc gtg act ttg gac ttc ccc act 4980
Thr Pro Glu Gly Glu Ile Gly Ala Val Thr Leu Asp Phe Pro Thr
1615 1620 1625
gga aca tca ggc tca cca ata gtg gac aaa aac ggt gat gtg att 5025
Gly Thr Ser Gly Ser Pro Ile Val Asp Lys Asn Gly Asp Val Ile
1630 1635 1640
ggg ctt tat ggc aat gga gtc ata atg ccc aac ggc tca tac ata 5070
Gly Leu Tyr Gly Asn Gly Val Ile Met Pro Asn Gly Ser Tyr Ile
1645 1650 1655
agc gcg ata gtg cag ggt gaa agg atg gat gag cca atc cca gcc 5115
Ser Ala Ile Val Gln Gly Glu Arg Met Asp Glu Pro Ile Pro Ala
1660 1665 1670
gga ttc gaa cct gag atg ctg agg aaa aaa cag atc act gta ctg 5160
Gly Phe Glu Pro Glu Met Leu Arg Lys Lys Gln Ile Thr Val Leu
1675 1680 1685
gat ctc cat ccc ggc gcc ggt aaa aca agg agg att ctg cca cag 5205
Asp Leu His Pro Gly Ala Gly Lys Thr Arg Arg Ile Leu Pro Gln
1690 1695 1700
atc atc aaa gag gcc ata aac aga aga ctg aga aca gcc gtg cta 5250
Ile Ile Lys Glu Ala Ile Asn Arg Arg Leu Arg Thr Ala Val Leu
1705 1710 1715
gca cca acc agg gtt gtg gct gct gag atg gct gaa gca ctg aga 5295
Ala Pro Thr Arg Val Val Ala Ala Glu Met Ala Glu Ala Leu Arg
1720 1725 1730
gga ctg ccc atc cgg tac cag aca tcc gca gtg ccc aga gaa cat 5340
Gly Leu Pro Ile Arg Tyr Gln Thr Ser Ala Val Pro Arg Glu His
1735 1740 1745
aat gga aat gag att gtt gat gtc atg tgt cat gct acc ctc acc 5385
Asn Gly Asn Glu Ile Val Asp Val Met Cys His Ala Thr Leu Thr
1750 1755 1760
cac agg ctg atg tct cct cac agg gtg ccg aac tac aac ctg ttc 5430
His Arg Leu Met Ser Pro His Arg Val Pro Asn Tyr Asn Leu Phe
1765 1770 1775
gtg atg gat gag gct cat ttc acc gac cca gct agc att gca gca 5475
Val Met Asp Glu Ala His Phe Thr Asp Pro Ala Ser Ile Ala Ala
1780 1785 1790
aga ggt tac att tcc aca aag gtc gag cta ggg gag gcg gcg gca 5520
Arg Gly Tyr Ile Ser Thr Lys Val Glu Leu Gly Glu Ala Ala Ala
1795 1800 1805
ata ttc atg aca gcc acc cca cca ggc act tca gat cca ttc cca 5565
Ile Phe Met Thr Ala Thr Pro Pro Gly Thr Ser Asp Pro Phe Pro
1810 1815 1820
gag tcc aat tca cca att tcc gac tta cag act gag atc ccg gat 5610
Glu Ser Asn Ser Pro Ile Ser Asp Leu Gln Thr Glu Ile Pro Asp
1825 1830 1835
cga gct tgg aac tct gga tac gaa tgg atc aca gaa tac acc ggg 5655
Arg Ala Trp Asn Ser Gly Tyr Glu Trp Ile Thr Glu Tyr Thr Gly
1840 1845 1850
aag acg gtt tgg ttt gtg cct agt gtc aag atg ggg aat gag att 5700
Lys Thr Val Trp Phe Val Pro Ser Val Lys Met Gly Asn Glu Ile
1855 1860 1865
gcc ctt tgc cta caa cgt gct gga aag aaa gta gtc caa ttg aac 5745
Ala Leu Cys Leu Gln Arg Ala Gly Lys Lys Val Val Gln Leu Asn
1870 1875 1880
aga aag tcg tac gag acg gag tac cca aaa tgt aag aac gat gat 5790
Arg Lys Ser Tyr Glu Thr Glu Tyr Pro Lys Cys Lys Asn Asp Asp
1885 1890 1895
tgg gac ttt gtt atc aca aca gac ata tct gaa atg ggg gct aac 5835
Trp Asp Phe Val Ile Thr Thr Asp Ile Ser Glu Met Gly Ala Asn
1900 1905 1910
ttc aag gcg agc agg gtg att gac agc cgg aag agt gtg aaa cca 5880
Phe Lys Ala Ser Arg Val Ile Asp Ser Arg Lys Ser Val Lys Pro
1915 1920 1925
acc atc ata aca gaa gga gaa ggg aga gtg atc ctg gga gaa cca 5925
Thr Ile Ile Thr Glu Gly Glu Gly Arg Val Ile Leu Gly Glu Pro
1930 1935 1940
tct gca gtg aca gca gct agt gcc gcc cag aga cgt gga cgt atc 5970
Ser Ala Val Thr Ala Ala Ser Ala Ala Gln Arg Arg Gly Arg Ile
1945 1950 1955
ggt aga aat ccg tcg caa gtt ggt gat gag tac tgt tat ggg ggg 6015
Gly Arg Asn Pro Ser Gln Val Gly Asp Glu Tyr Cys Tyr Gly Gly
1960 1965 1970
cac acg aat gaa gac gac tcg aac ttc gcc cat tgg act gag gca 6060
His Thr Asn Glu Asp Asp Ser Asn Phe Ala His Trp Thr Glu Ala
1975 1980 1985
cga atc atg ctg gac aac atc aac atg cca aac gga ctg atc gct 6105
Arg Ile Met Leu Asp Asn Ile Asn Met Pro Asn Gly Leu Ile Ala
1990 1995 2000
caa ttc tac caa cca gag cgt gag aag gta tat acc atg gat ggg 6150
Gln Phe Tyr Gln Pro Glu Arg Glu Lys Val Tyr Thr Met Asp Gly
2005 2010 2015
gaa tac cgg ctc aga gga gaa gag aga aaa aac ttt ctg gaa ctg 6195
Glu Tyr Arg Leu Arg Gly Glu Glu Arg Lys Asn Phe Leu Glu Leu
2020 2025 2030
ttg agg act gca gat ctg cca gtt tgg ctg gct tac aag gtt gca 6240
Leu Arg Thr Ala Asp Leu Pro Val Trp Leu Ala Tyr Lys Val Ala
2035 2040 2045
gcg gct gga gtg tca tac cac gac cgg agg tgg tgc ttt gat ggt 6285
Ala Ala Gly Val Ser Tyr His Asp Arg Arg Trp Cys Phe Asp Gly
2050 2055 2060
cct agg aca aac aca att tta gaa gac aac aac gaa gtg gaa gtc 6330
Pro Arg Thr Asn Thr Ile Leu Glu Asp Asn Asn Glu Val Glu Val
2065 2070 2075
atc acg aag ctt ggt gaa agg aag att ctg agg ccg cgc tgg att 6375
Ile Thr Lys Leu Gly Glu Arg Lys Ile Leu Arg Pro Arg Trp Ile
2080 2085 2090
gac gcc agg gtg tac tcg gat cac cag gca cta aag gcg ttc aag 6420
Asp Ala Arg Val Tyr Ser Asp His Gln Ala Leu Lys Ala Phe Lys
2095 2100 2105
gac ttc gcc tcg gga aaa cgt tct cag ata ggg ctc att gag gtt 6465
Asp Phe Ala Ser Gly Lys Arg Ser Gln Ile Gly Leu Ile Glu Val
2110 2115 2120
ctg gga aag atg cct gag cac ttc atg ggg aag aca tgg gaa gca 6510
Leu Gly Lys Met Pro Glu His Phe Met Gly Lys Thr Trp Glu Ala
2125 2130 2135
ctt gac acc atg tac gtt gtg gcc act gca gag aaa gga gga aga 6555
Leu Asp Thr Met Tyr Val Val Ala Thr Ala Glu Lys Gly Gly Arg
2140 2145 2150
gct cac aga atg gcc ctg gag gaa ctg cca gat gct ctt cag aca 6600
Ala His Arg Met Ala Leu Glu Glu Leu Pro Asp Ala Leu Gln Thr
2155 2160 2165
att gcc ttg att gcc tta ttg agt gtg atg acc atg gga gta ttc 6645
Ile Ala Leu Ile Ala Leu Leu Ser Val Met Thr Met Gly Val Phe
2170 2175 2180
ttc ctc ctc atg cag cgg aag ggc att gga aag ata ggt ttg gga 6690
Phe Leu Leu Met Gln Arg Lys Gly Ile Gly Lys Ile Gly Leu Gly
2185 2190 2195
ggc gct gtc ttg gga gtc gcg acc ttt ttc tgt tgg atg gct gaa 6735
Gly Ala Val Leu Gly Val Ala Thr Phe Phe Cys Trp Met Ala Glu
2200 2205 2210
gtt cca gga acg aag atc gcc gga atg ttg ctg ctc tcc ctt ctc 6780
Val Pro Gly Thr Lys Ile Ala Gly Met Leu Leu Leu Ser Leu Leu
2215 2220 2225
ttg atg att gtg cta att cct gag cca gag aag caa cgt tcg cag 6825
Leu Met Ile Val Leu Ile Pro Glu Pro Glu Lys Gln Arg Ser Gln
2230 2235 2240
aca gac aac cag cta gcc gtg ttc ctg att tgt gtc atg acc ctt 6870
Thr Asp Asn Gln Leu Ala Val Phe Leu Ile Cys Val Met Thr Leu
2245 2250 2255
gtg agc gca gtg gca gcc aac gag atg ggt tgg cta gat aag acc 6915
Val Ser Ala Val Ala Ala Asn Glu Met Gly Trp Leu Asp Lys Thr
2260 2265 2270
aag agt gac ata agc agt ttg ttt ggg caa aga att gag gtc aag 6960
Lys Ser Asp Ile Ser Ser Leu Phe Gly Gln Arg Ile Glu Val Lys
2275 2280 2285
gag aat ttc agc atg gga gag ttt ctt ttg gac ttg agg cct gca 7005
Glu Asn Phe Ser Met Gly Glu Phe Leu Leu Asp Leu Arg Pro Ala
2290 2295 2300
aca gcc tgg tca ctg tac gct gtg aca aca gcg gtc ctc act cca 7050
Thr Ala Trp Ser Leu Tyr Ala Val Thr Thr Ala Val Leu Thr Pro
2305 2310 2315
ctg cta aag cat ttg atc acg tca gat tac atc aac acc tca ttg 7095
Leu Leu Lys His Leu Ile Thr Ser Asp Tyr Ile Asn Thr Ser Leu
2320 2325 2330
acc tca ata aac gtt cag gca agt gca cta ttc aca ctc gcg cga 7140
Thr Ser Ile Asn Val Gln Ala Ser Ala Leu Phe Thr Leu Ala Arg
2335 2340 2345
ggc ttc ccc ttc gtc gat gtt gga gtg tcg gct ctc ctg cta gca 7185
Gly Phe Pro Phe Val Asp Val Gly Val Ser Ala Leu Leu Leu Ala
2350 2355 2360
gcc gga tgc tgg gga caa gtc acc ctc acc gtt acg gta aca gcg 7230
Ala Gly Cys Trp Gly Gln Val Thr Leu Thr Val Thr Val Thr Ala
2365 2370 2375
gca aca ctc ctt ttt tgc cac tat gcc tac atg gtt ccc ggt tgg 7275
Ala Thr Leu Leu Phe Cys His Tyr Ala Tyr Met Val Pro Gly Trp
2380 2385 2390
caa gct gag gca atg cgc tca gcc cag cgg cgg aca gcg gcc gga 7320
Gln Ala Glu Ala Met Arg Ser Ala Gln Arg Arg Thr Ala Ala Gly
2395 2400 2405
atc atg aag aac gct gta gtg gat ggc atc gtg gcc acg gac gtc 7365
Ile Met Lys Asn Ala Val Val Asp Gly Ile Val Ala Thr Asp Val
2410 2415 2420
cca gaa tta gag cgc acc aca ccc atc atg cag aag aaa gtt gga 7410
Pro Glu Leu Glu Arg Thr Thr Pro Ile Met Gln Lys Lys Val Gly
2425 2430 2435
cag atc atg ctg atc ttg gtg tct cta gct gca gta gta gtg aac 7455
Gln Ile Met Leu Ile Leu Val Ser Leu Ala Ala Val Val Val Asn
2440 2445 2450
ccg tct gtg aag aca gta cga gaa gcc gga att ttg atc acg gcc 7500
Pro Ser Val Lys Thr Val Arg Glu Ala Gly Ile Leu Ile Thr Ala
2455 2460 2465
gca gcg gtg acg ctt tgg gag aat gga gca agc tct gtt tgg aac 7545
Ala Ala Val Thr Leu Trp Glu Asn Gly Ala Ser Ser Val Trp Asn
2470 2475 2480
gca aca act gcc atc gga ctc tgc cac atc atg cgt ggg ggt tgg 7590
Ala Thr Thr Ala Ile Gly Leu Cys His Ile Met Arg Gly Gly Trp
2485 2490 2495
ttg tca tgt cta tcc ata aca tgg aca ctc ata aag aac atg gaa 7635
Leu Ser Cys Leu Ser Ile Thr Trp Thr Leu Ile Lys Asn Met Glu
2500 2505 2510
aaa cca gga cta aaa aga ggt ggg gca aaa gga cgc acc ttg gga 7680
Lys Pro Gly Leu Lys Arg Gly Gly Ala Lys Gly Arg Thr Leu Gly
2515 2520 2525
gag gtt tgg aaa gaa aga ctc aac cag atg aca aaa gaa gag ttc 7725
Glu Val Trp Lys Glu Arg Leu Asn Gln Met Thr Lys Glu Glu Phe
2530 2535 2540
act agg tac cgc aaa gag gcc atc atc gaa gtc gat cgc tca gcg 7770
Thr Arg Tyr Arg Lys Glu Ala Ile Ile Glu Val Asp Arg Ser Ala
2545 2550 2555
gca aaa cac gcc agg aaa gaa ggc aat gtc act gga ggg cat cca 7815
Ala Lys His Ala Arg Lys Glu Gly Asn Val Thr Gly Gly His Pro
2560 2565 2570
gtc tct agg ggc aca gca aaa ctg aga tgg ctg gtc gaa cgg agg 7860
Val Ser Arg Gly Thr Ala Lys Leu Arg Trp Leu Val Glu Arg Arg
2575 2580 2585
ttt ctc gaa ccg gtc gga aaa gtg att gac ctt gga tgt gga aga 7905
Phe Leu Glu Pro Val Gly Lys Val Ile Asp Leu Gly Cys Gly Arg
2590 2595 2600
ggc ggt tgg tgt tac tat atg gca acc caa aaa aga gtc caa gaa 7950
Gly Gly Trp Cys Tyr Tyr Met Ala Thr Gln Lys Arg Val Gln Glu
2605 2610 2615
gtc aga ggg tac aca aag ggc ggt ccc gga cat gaa gag ccc caa 7995
Val Arg Gly Tyr Thr Lys Gly Gly Pro Gly His Glu Glu Pro Gln
2620 2625 2630
cta gtg caa agt tat gga tgg aac att gtc acc atg aag agt gga 8040
Leu Val Gln Ser Tyr Gly Trp Asn Ile Val Thr Met Lys Ser Gly
2635 2640 2645
gtg gat gtg ttc tac aga cct tct gag tgt tgt gac acc ctc ctt 8085
Val Asp Val Phe Tyr Arg Pro Ser Glu Cys Cys Asp Thr Leu Leu
2650 2655 2660
tgt gac atc gga gag tcc tcg tca agt gct gag gtt gaa gag cat 8130
Cys Asp Ile Gly Glu Ser Ser Ser Ser Ala Glu Val Glu Glu His
2665 2670 2675
agg acg att cgg gtc ctt gaa atg gtt gag gac tgg ctg cac cga 8175
Arg Thr Ile Arg Val Leu Glu Met Val Glu Asp Trp Leu His Arg
2680 2685 2690
ggg cca agg gaa ttt tgc gtg aag gtg ctc tgc ccc tac atg ccg 8220
Gly Pro Arg Glu Phe Cys Val Lys Val Leu Cys Pro Tyr Met Pro
2695 2700 2705
aaa gtc ata gag aag atg gag ctg ctc caa cgc cgg tat ggg ggg 8265
Lys Val Ile Glu Lys Met Glu Leu Leu Gln Arg Arg Tyr Gly Gly
2710 2715 2720
gga ctg gtc aga aac cca ctc tca cgg aat tcc acg cac gag atg 8310
Gly Leu Val Arg Asn Pro Leu Ser Arg Asn Ser Thr His Glu Met
2725 2730 2735
tat tgg gtg agt cga gct tca ggc aat gtg gta cat tca gtg aat 8355
Tyr Trp Val Ser Arg Ala Ser Gly Asn Val Val His Ser Val Asn
2740 2745 2750
atg acc agc cag gtg ctc cta gga aga atg gaa aaa agg acc tgg 8400
Met Thr Ser Gln Val Leu Leu Gly Arg Met Glu Lys Arg Thr Trp
2755 2760 2765
aag gga ccc caa tac gag gaa gat gta aac ttg gga agt gga acc 8445
Lys Gly Pro Gln Tyr Glu Glu Asp Val Asn Leu Gly Ser Gly Thr
2770 2775 2780
agg gcg gtg gga aaa ccc ctg ctc aac tca gac acc agt aaa atc 8490
Arg Ala Val Gly Lys Pro Leu Leu Asn Ser Asp Thr Ser Lys Ile
2785 2790 2795
aag aac agg att gaa cga ctc agg cgt gag tac agt tcg acg tgg 8535
Lys Asn Arg Ile Glu Arg Leu Arg Arg Glu Tyr Ser Ser Thr Trp
2800 2805 2810
cac cac gat gag aac cac cca tat aga acc tgg aac tat cac ggc 8580
His His Asp Glu Asn His Pro Tyr Arg Thr Trp Asn Tyr His Gly
2815 2820 2825
agt tat gat gtg aag ccc aca ggc tcc gcc agt tcg ctg gtc aat 8625
Ser Tyr Asp Val Lys Pro Thr Gly Ser Ala Ser Ser Leu Val Asn
2830 2835 2840
gga gtg gtc agg ctc ctc tca aaa cca tgg gac acc atc acg aat 8670
Gly Val Val Arg Leu Leu Ser Lys Pro Trp Asp Thr Ile Thr Asn
2845 2850 2855
gtt acc acc atg gcc atg act gac act act ccc ttc ggg cag cag 8715
Val Thr Thr Met Ala Met Thr Asp Thr Thr Pro Phe Gly Gln Gln
2860 2865 2870
cga gtg ttc aaa gag aag gtg gac acg aaa gct cct gaa ccg cca 8760
Arg Val Phe Lys Glu Lys Val Asp Thr Lys Ala Pro Glu Pro Pro
2875 2880 2885
gaa gga gtg aag tac gtg ctc aac gag acc acc aac tgg ttg tgg 8805
Glu Gly Val Lys Tyr Val Leu Asn Glu Thr Thr Asn Trp Leu Trp
2890 2895 2900
gcg ttt ttg gcc aga gaa aaa cgt ccc aga atg tgc tct cga gag 8850
Ala Phe Leu Ala Arg Glu Lys Arg Pro Arg Met Cys Ser Arg Glu
2905 2910 2915
gaa ttc ata aga aag gtc aac agc aat gca gct ttg ggt gcc atg 8895
Glu Phe Ile Arg Lys Val Asn Ser Asn Ala Ala Leu Gly Ala Met
2920 2925 2930
ttt gaa gag cag aat caa tgg agg agc gcc aga gaa gca gtt gaa 8940
Phe Glu Glu Gln Asn Gln Trp Arg Ser Ala Arg Glu Ala Val Glu
2935 2940 2945
gat cca aaa ttt tgg gag atg gtg gat gag gag cgc gag gca cat 8985
Asp Pro Lys Phe Trp Glu Met Val Asp Glu Glu Arg Glu Ala His
2950 2955 2960
ctg cgg ggg gaa tgt cac act tgc att tac aac atg atg gga aag 9030
Leu Arg Gly Glu Cys His Thr Cys Ile Tyr Asn Met Met Gly Lys
2965 2970 2975
aga gag aaa aaa ccc gga gag ttc gga aag gcc aag gga agc aga 9075
Arg Glu Lys Lys Pro Gly Glu Phe Gly Lys Ala Lys Gly Ser Arg
2980 2985 2990
gcc att tgg ttc atg tgg ctc gga gct cgc ttt ctg gag ttc gag 9120
Ala Ile Trp Phe Met Trp Leu Gly Ala Arg Phe Leu Glu Phe Glu
2995 3000 3005
gct ctg ggt ttt ctc aat gaa gac cac tgg ctt gga aga aag aac 9165
Ala Leu Gly Phe Leu Asn Glu Asp His Trp Leu Gly Arg Lys Asn
3010 3015 3020
tca gga gga ggt gtc gag ggc ttg ggc ctc caa aaa ctg ggt tac 9210
Ser Gly Gly Gly Val Glu Gly Leu Gly Leu Gln Lys Leu Gly Tyr
3025 3030 3035
atc ctg cgt gaa gtt ggc acc cgg cct ggg ggc aag atc tat gct 9255
Ile Leu Arg Glu Val Gly Thr Arg Pro Gly Gly Lys Ile Tyr Ala
3040 3045 3050
gat gac aca gct ggc tgg gac acc cgc atc acg aga gct gac ttg 9300
Asp Asp Thr Ala Gly Trp Asp Thr Arg Ile Thr Arg Ala Asp Leu
3055 3060 3065
gaa aat gaa gct aag gtg ctt gag ctg ctt gat ggg gaa cat cgg 9345
Glu Asn Glu Ala Lys Val Leu Glu Leu Leu Asp Gly Glu His Arg
3070 3075 3080
cgt ctt gcc agg gcc atc att gag ctc acc tat cgt cac aaa gtt 9390
Arg Leu Ala Arg Ala Ile Ile Glu Leu Thr Tyr Arg His Lys Val
3085 3090 3095
gtg aaa gtg atg cgc ccg gct gct gat gga aga acc gtc atg gat 9435
Val Lys Val Met Arg Pro Ala Ala Asp Gly Arg Thr Val Met Asp
3100 3105 3110
gtt atc tcc aga gaa gat cag agg ggg agt gga caa gtt gtc acc 9480
Val Ile Ser Arg Glu Asp Gln Arg Gly Ser Gly Gln Val Val Thr
3115 3120 3125
tac gcc cta aac act ttc acc aac ctg gcc gtc cag ctg gtg agg 9525
Tyr Ala Leu Asn Thr Phe Thr Asn Leu Ala Val Gln Leu Val Arg
3130 3135 3140
atg atg gaa ggg gaa gga gtg att ggc cca gat gat gtg gag aaa 9570
Met Met Glu Gly Glu Gly Val Ile Gly Pro Asp Asp Val Glu Lys
3145 3150 3155
ctc aca aaa ggg aaa gga ccc aaa gtc agg acc tgg ctg ttt gag 9615
Leu Thr Lys Gly Lys Gly Pro Lys Val Arg Thr Trp Leu Phe Glu
3160 3165 3170
aat ggg gaa gaa aga ctc agc cgc atg gct gtc agt gga gat gac 9660
Asn Gly Glu Glu Arg Leu Ser Arg Met Ala Val Ser Gly Asp Asp
3175 3180 3185
tgt gtg gta aag ccc ctg gac gat cgc ttt gcc acc tcg ctc cac 9705
Cys Val Val Lys Pro Leu Asp Asp Arg Phe Ala Thr Ser Leu His
3190 3195 3200
ttc ctc aat gct atg tca aag gtt cgc aaa gac atc caa gag tgg 9750
Phe Leu Asn Ala Met Ser Lys Val Arg Lys Asp Ile Gln Glu Trp
3205 3210 3215
aaa ccg tca act gga tgg tat gat tgg cag cag gtt cca ttt tgc 9795
Lys Pro Ser Thr Gly Trp Tyr Asp Trp Gln Gln Val Pro Phe Cys
3220 3225 3230
tca aac cat ttc act gaa ttg atc atg aaa gat gga aga aca ctg 9840
Ser Asn His Phe Thr Glu Leu Ile Met Lys Asp Gly Arg Thr Leu
3235 3240 3245
gtg gtt cca tgc cga gga cag gat gaa ttg gta ggc aga gct cgc 9885
Val Val Pro Cys Arg Gly Gln Asp Glu Leu Val Gly Arg Ala Arg
3250 3255 3260
ata tct cca ggg gcc gga tgg aac gtc cgc gac act gct tgt ctg 9930
Ile Ser Pro Gly Ala Gly Trp Asn Val Arg Asp Thr Ala Cys Leu
3265 3270 3275
gct aag tct tat gcc cag atg tgg ctg ctt ctg tac ttc cac aga 9975
Ala Lys Ser Tyr Ala Gln Met Trp Leu Leu Leu Tyr Phe His Arg
3280 3285 3290
aga gac ctg cgg ctc atg gcc aac gcc att tgc tcc gct gtc cct 10020
Arg Asp Leu Arg Leu Met Ala Asn Ala Ile Cys Ser Ala Val Pro
3295 3300 3305
gtg aat tgg gtc cct acc gga aga acc acg tgg tcc atc cat gca 10065
Val Asn Trp Val Pro Thr Gly Arg Thr Thr Trp Ser Ile His Ala
3310 3315 3320
gga gga gag tgg atg aca aca gag gac atg ttg gag gtc tgg aac 10110
Gly Gly Glu Trp Met Thr Thr Glu Asp Met Leu Glu Val Trp Asn
3325 3330 3335
cgt gtt tgg ata gag gag aat gaa tgg atg gaa gac aaa acc cca 10155
Arg Val Trp Ile Glu Glu Asn Glu Trp Met Glu Asp Lys Thr Pro
3340 3345 3350
gtg gag aaa tgg agt gac gtc cca tat tca gga aaa cga gag gac 10200
Val Glu Lys Trp Ser Asp Val Pro Tyr Ser Gly Lys Arg Glu Asp
3355 3360 3365
atc tgg tgt ggc agc ctg att ggc aca aga gcc cga gcc acg tgg 10245
Ile Trp Cys Gly Ser Leu Ile Gly Thr Arg Ala Arg Ala Thr Trp
3370 3375 3380
gca gaa aac atc cag gtg gct atc aac caa gtc aga gca atc atc 10290
Ala Glu Asn Ile Gln Val Ala Ile Asn Gln Val Arg Ala Ile Ile
3385 3390 3395
gga gat gag aag tat gtg gat tac atg agt tca cta aag aga tat 10335
Gly Asp Glu Lys Tyr Val Asp Tyr Met Ser Ser Leu Lys Arg Tyr
3400 3405 3410
gaa gac aca act ttg gtt gag gac aca gta ctg tag atatttaatc 10381
Glu Asp Thr Thr Leu Val Glu Asp Thr Val Leu
3415 3420
aattgtaaat agacaatata agtatgcata aaagtgtagt tttatagtag tatttagtgg10441
tgttagtgta aatagttaag aaaattttga ggagaaagtc aggccgggaa gttcccgcca10501
ccggaagttg agtagacggt gctgcctgcg actcaacccc aggaggactg ggtgaacaaa10561
gccgcgaagt gatccatgta agccctcaga accgtctcgg aaggaggacc ccacatgttg10621
taacttcaaa gcccaatgtc agaccacgct acggcgtgct actctgcgga gagtgcagtc10681
tgcgatagtg ccccaggagg actgggttaa caaaggcaaa ccaacgcccc acgcggccct10741
agccccggta atggtgttaa ccagggcgaa aggactagag gttagaggag accccgcggt10801
ttaaagtgca cggcccagcc tggctgaagc tgtaggtcag gggaaggact agaggttagt10861
ggagaccccg tgccacaaaa caccacaaca aaacagcata ttgacacctg ggatagacta10921
ggagatcttc tgctctgcac aaccagccac acggcacagt gcgccgacaa tggtggctgg10981
tggtgcgaga acacaggatc t 11002
<210> 18
<211> 3424
<212> PRT
<213> 人工序列
<220>
<223> 合成的构建体
<400> 18
Met Ser Lys Lys Pro Gly Gly Pro Gly Lys Ser Arg Ala Val Asn Met
1 5 10 15
Leu Lys Arg Gly Met Pro Arg Val Leu Ser Leu Ile Gly Leu Lys Arg
20 25 30
Ala Met Leu Ser Leu Ile Asp Gly Lys Gly Pro Ile Arg Phe Val Leu
35 40 45
Ala Leu Leu Ala Phe Phe Arg Phe Thr Ala Ile Ala Pro Thr Arg Ala
50 55 60
Val Leu Asp Arg Trp Arg Gly Val Asn Lys Gln Thr Ala Met Lys His
65 70 75 80
Leu Leu Ser Phe Lys Lys Glu Leu Gly Thr Leu Thr Ser Ala Ile Asn
85 90 95
Arg Arg Ser Ser Lys Gln Lys Lys Arg Gly Gly Lys Thr Gly Ile Ala
100 105 110
Val Met Ile Gly Leu Ile Ala Ser Val Gly Ala Phe His Leu Thr Ser
115 120 125
Arg Asp Gly Glu Pro Arg Met Ile Val Gly Lys Asn Glu Arg Gly Lys
130 135 140
Ser Leu Leu Phe Lys Thr Ala Ser Gly Ile Asn Met Cys Thr Leu Ile
145 150 155 160
Ala Met Asp Leu Gly Glu Met Cys Asp Asp Thr Val Thr Tyr Lys Cys
165 170 175
Pro His Ile Thr Glu Val Glu Pro Glu Asp Ile Asp Cys Trp Cys Asn
180 185 190
Leu Thr Ser Thr Trp Val Thr Tyr Gly Thr Cys Asn Gln Ala Gly Glu
195 200 205
His Arg Arg Asp Lys Arg Ser Val Ala Leu Ala Pro His Val Gly Met
210 215 220
Gly Leu Asp Thr Arg Thr Gln Thr Trp Met Ser Ala Glu Gly Ala Trp
225 230 235 240
Arg Gln Val Glu Lys Val Glu Thr Trp Ala Leu Arg His Pro Gly Phe
245 250 255
Thr Ile Leu Ala Leu Phe Leu Ala His Tyr Ile Gly Thr Ser Leu Thr
260 265 270
Gln Lys Val Val Ile Phe Ile Leu Leu Met Leu Val Thr Pro Ser Met
275 280 285
Thr Met Arg Cys Val Gly Val Gly Asn Arg Asp Phe Val Glu Gly Leu
290 295 300
Ser Gly Ala Thr Trp Val Asp Val Val Leu Glu His Gly Gly Cys Val
305 310 315 320
Thr Thr Met Ala Lys Asn Lys Pro Thr Leu Asp Ile Glu Leu Gln Lys
325 330 335
Thr Glu Ala Thr Gln Leu Ala Thr Leu Arg Lys Leu Cys Ile Glu Gly
340 345 350
Lys Ile Thr Asn Ile Thr Thr Asp Ser Arg Cys Pro Thr Gln Gly Glu
355 360 365
Ala Ile Leu Pro Glu Glu Gln Asp Gln Asn Tyr Val Cys Lys His Thr
370 375 380
Tyr Val Asp Arg Gly Trp Gly Asn Gly Cys Gly Leu Phe Gly Lys Gly
385 390 395 400
Ser Leu Val Thr Cys Ala Lys Phe Gln Cys Leu Glu Ser Ile Glu Gly
405 410 415
Lys Val Val Gln His Glu Asn Leu Lys Tyr Thr Val Ile Ile Thr Val
420 425 430
His Thr Gly Asp Gln His Gln Val Gly Asn Glu Thr Gln Gly Val Thr
435 440 445
Ala Glu Ile Thr Pro Gln Ala Ser Thr Ala Glu Ala Ile Leu Pro Glu
450 455 460
Tyr Gly Thr Leu Gly Leu Glu Cys Ser Pro Arg Thr Gly Leu Asp Phe
465 470 475 480
Asn Glu Met Ile Ser Leu Thr Met Lys Asn Lys Ala Trp Met Val His
485 490 495
Arg Gln Trp Phe Phe Asp Leu Pro Leu Pro Trp Thr Ser Gly Ala Thr
500 505 510
Ala Glu Thr Pro Thr Trp Asn Arg Lys Glu Leu Leu Val Thr Phe Lys
515 520 525
Asn Ala His Ala Lys Lys Gln Glu Val Val Val Leu Gly Ser Gln Glu
530 535 540
Gly Ala Met His Thr Ala Leu Thr Gly Ala Thr Glu Ile Gln Thr Ser
545 550 555 560
Gly Gly Thr Ser Ile Phe Ala Gly His Leu Lys Cys Arg Leu Lys Met
565 570 575
Asp Lys Leu Glu Leu Lys Gly Met Ser Tyr Ala Met Cys Leu Ser Ser
580 585 590
Phe Val Leu Lys Lys Glu Val Ser Glu Thr Gln His Gly Thr Ile Leu
595 600 605
Ile Lys Val Glu Tyr Lys Gly Glu Asp Ala Pro Cys Lys Ile Pro Phe
610 615 620
Ser Thr Glu Asp Gly Gln Gly Lys Ala Leu Asn Gly Arg Leu Ile Thr
625 630 635 640
Ala Asn Pro Val Val Thr Lys Lys Glu Glu Pro Val Asn Ile Glu Ala
645 650 655
Glu Pro Pro Phe Gly Glu Ser Asn Ile Val Ile Gly Ile Gly Asp Lys
660 665 670
Ala Leu Lys Ile Asn Trp Tyr Lys Lys Gly Ser Ser Ile Gly Lys Met
675 680 685
Phe Glu Ala Thr Ala Arg Gly Ala Arg Arg Met Ala Ile Leu Gly Asp
690 695 700
Thr Ala Trp Asp Phe Gly Ser Val Gly Gly Val Leu Asn Ser Leu Gly
705 710 715 720
Lys Met Val His Gln Ile Phe Gly Ser Ala Tyr Thr Ala Leu Phe Gly
725 730 735
Gly Val Ser Trp Met Met Lys Ile Gly Ile Gly Val Leu Leu Thr Trp
740 745 750
Ile Gly Leu Asn Ser Lys Asn Thr Ser Met Ser Phe Ser Cys Ile Ala
755 760 765
Ile Gly Ile Ile Thr Leu Tyr Leu Gly Ala Val Val Gln Ala Asp Ser
770 775 780
Gly Cys Ala Ile Asp Ile Ser Arg Gln Glu Leu Arg Cys Gly Ser Gly
785 790 795 800
Val Phe Ile His Asn Asp Val Glu Ala Trp Met Asp Arg Tyr Lys Tyr
805 810 815
Tyr Pro Glu Thr Pro Gln Gly Leu Ala Lys Ile Ile Gln Lys Ala His
820 825 830
Lys Glu Gly Val Cys Gly Leu Arg Ser Val Ser Arg Leu Glu His Gln
835 840 845
Met Trp Glu Ala Val Lys Asp Glu Leu Asn Thr Leu Leu Lys Glu Asn
850 855 860
Gly Val Asp Leu Ser Val Val Val Glu Lys Gln Glu Gly Met Tyr Lys
865 870 875 880
Ser Ala Pro Lys Arg Leu Thr Ala Thr Thr Glu Lys Leu Glu Ile Gly
885 890 895
Trp Lys Ala Trp Gly Lys Ser Ile Leu Phe Ala Pro Glu Leu Ala Asn
900 905 910
Asn Thr Phe Val Val Asp Gly Pro Glu Thr Lys Glu Cys Pro Thr Gln
915 920 925
Asn Arg Ala Trp Asn Ser Leu Glu Val Glu Asp Phe Gly Phe Gly Leu
930 935 940
Thr Ser Thr Arg Met Phe Leu Lys Val Arg Glu Ser Asn Thr Thr Glu
945 950 955 960
Cys Asp Ser Lys Ile Ile Gly Thr Ala Val Lys Asn Asn Leu Ala Ile
965 970 975
His Ser Asp Leu Ser Tyr Trp Ile Glu Ser Arg Leu Asn Asp Thr Trp
980 985 990
Lys Leu Glu Arg Ala Val Leu Gly Glu Val Lys Ser Cys Thr Trp Pro
995 1000 1005
Glu Thr His Thr Leu Trp Gly Asp Gly Ile Leu Glu Ser Asp Leu
1010 1015 1020
Ile Ile Pro Val Thr Leu Ala Gly Pro Arg Ser Asn His Asn Arg
1025 1030 1035
Arg Pro Gly Tyr Lys Thr Gln Asn Gln Gly Pro Trp Asp Glu Gly
1040 1045 1050
Arg Val Glu Ile Asp Phe Asp Tyr Cys Pro Gly Thr Thr Val Thr
1055 1060 1065
Leu Ser Glu Ser Cys Gly His Arg Gly Pro Ala Thr Arg Thr Thr
1070 1075 1080
Thr Glu Ser Gly Lys Leu Ile Thr Asp Trp Cys Cys Arg Ser Cys
1085 1090 1095
Thr Leu Pro Pro Leu Arg Tyr Gln Thr Asp Ser Gly Cys Trp Tyr
1100 1105 1110
Gly Met Glu Ile Arg Pro Gln Arg His Asp Glu Lys Thr Leu Val
1115 1120 1125
Gln Ser Gln Val Asn Ala Tyr Asn Ala Asp Met Ile Asp Pro Phe
1130 1135 1140
Gln Leu Gly Leu Leu Val Val Phe Leu Ala Thr Gln Glu Val Leu
1145 1150 1155
Arg Lys Arg Trp Thr Ala Lys Ile Ser Met Pro Ala Ile Leu Ile
1160 1165 1170
Ala Leu Leu Val Leu Val Phe Gly Gly Ile Thr Tyr Thr Asp Val
1175 1180 1185
Leu Arg Tyr Val Ile Leu Val Gly Ala Ala Phe Ala Glu Ser Asn
1190 1195 1200
Ser Gly Gly Asp Val Val His Leu Ala Leu Met Ala Thr Phe Lys
1205 1210 1215
Ile Gln Pro Val Phe Met Val Ala Ser Phe Leu Lys Ala Arg Trp
1220 1225 1230
Thr Asn Gln Glu Asn Ile Leu Leu Met Leu Ala Ala Val Phe Phe
1235 1240 1245
Gln Met Ala Tyr Tyr Asp Ala Arg Gln Ile Leu Leu Trp Glu Ile
1250 1255 1260
Pro Asp Val Leu Asn Ser Leu Ala Val Ala Trp Met Ile Leu Arg
1265 1270 1275
Ala Ile Thr Phe Thr Thr Thr Ser Asn Val Val Val Pro Leu Leu
1280 1285 1290
Ala Leu Leu Thr Pro Gly Leu Arg Cys Leu Asn Leu Asp Val Tyr
1295 1300 1305
Arg Ile Leu Leu Leu Met Val Gly Ile Gly Ser Leu Ile Arg Glu
1310 1315 1320
Lys Arg Ser Ala Ala Ala Lys Lys Lys Gly Ala Ser Leu Leu Cys
1325 1330 1335
Leu Ala Leu Ala Ser Thr Gly Leu Phe Asn Pro Met Ile Leu Ala
1340 1345 1350
Ala Gly Leu Ile Ala Cys Asp Pro Asn Arg Lys Arg Gly Trp Pro
1355 1360 1365
Ala Thr Glu Val Met Thr Ala Val Gly Leu Met Phe Ala Ile Val
1370 1375 1380
Gly Gly Leu Ala Glu Leu Asp Ile Asp Ser Met Ala Ile Pro Met
1385 1390 1395
Thr Ile Ala Gly Leu Met Phe Ala Ala Phe Val Ile Ser Gly Lys
1400 1405 1410
Ser Thr Asp Met Trp Ile Glu Arg Thr Ala Asp Ile Ser Trp Glu
1415 1420 1425
Ser Asp Ala Glu Ile Thr Gly Ser Ser Glu Arg Val Asp Val Arg
1430 1435 1440
Leu Asp Asp Asp Gly Asn Phe Gln Leu Met Asn Asp Pro Gly Ala
1445 1450 1455
Pro Trp Lys Ile Trp Met Leu Arg Met Val Cys Leu Ala Ile Ser
1460 1465 1470
Ala Tyr Thr Pro Trp Ala Ile Leu Pro Ser Val Val Gly Phe Trp
1475 1480 1485
Ile Thr Leu Gln Tyr Thr Lys Arg Gly Gly Val Leu Trp Asp Thr
1490 1495 1500
Pro Ser Pro Lys Glu Tyr Lys Lys Gly Asp Thr Thr Thr Gly Val
1505 1510 1515
Tyr Arg Ile Met Thr Arg Gly Leu Leu Gly Ser Tyr Gln Ala Gly
1520 1525 1530
Ala Gly Val Met Val Glu Gly Val Phe His Thr Leu Trp His Thr
1535 1540 1545
Thr Lys Gly Ala Ala Leu Met Ser Gly Glu Gly Arg Leu Asp Pro
1550 1555 1560
Tyr Trp Gly Ser Val Lys Glu Asp Arg Leu Cys Tyr Gly Gly Pro
1565 1570 1575
Trp Lys Leu Gln His Lys Trp Asn Gly Gln Asp Glu Val Gln Met
1580 1585 1590
Ile Val Val Glu Pro Gly Arg Asn Val Lys Asn Val Gln Thr Lys
1595 1600 1605
Pro Gly Val Phe Lys Thr Pro Glu Gly Glu Ile Gly Ala Val Thr
1610 1615 1620
Leu Asp Phe Pro Thr Gly Thr Ser Gly Ser Pro Ile Val Asp Lys
1625 1630 1635
Asn Gly Asp Val Ile Gly Leu Tyr Gly Asn Gly Val Ile Met Pro
1640 1645 1650
Asn Gly Ser Tyr Ile Ser Ala Ile Val Gln Gly Glu Arg Met Asp
1655 1660 1665
Glu Pro Ile Pro Ala Gly Phe Glu Pro Glu Met Leu Arg Lys Lys
1670 1675 1680
Gln Ile Thr Val Leu Asp Leu His Pro Gly Ala Gly Lys Thr Arg
1685 1690 1695
Arg Ile Leu Pro Gln Ile Ile Lys Glu Ala Ile Asn Arg Arg Leu
1700 1705 1710
Arg Thr Ala Val Leu Ala Pro Thr Arg Val Val Ala Ala Glu Met
1715 1720 1725
Ala Glu Ala Leu Arg Gly Leu Pro Ile Arg Tyr Gln Thr Ser Ala
1730 1735 1740
Val Pro Arg Glu His Asn Gly Asn Glu Ile Val Asp Val Met Cys
1745 1750 1755
His Ala Thr Leu Thr His Arg Leu Met Ser Pro His Arg Val Pro
1760 1765 1770
Asn Tyr Asn Leu Phe Val Met Asp Glu Ala His Phe Thr Asp Pro
1775 1780 1785
Ala Ser Ile Ala Ala Arg Gly Tyr Ile Ser Thr Lys Val Glu Leu
1790 1795 1800
Gly Glu Ala Ala Ala Ile Phe Met Thr Ala Thr Pro Pro Gly Thr
1805 1810 1815
Ser Asp Pro Phe Pro Glu Ser Asn Ser Pro Ile Ser Asp Leu Gln
1820 1825 1830
Thr Glu Ile Pro Asp Arg Ala Trp Asn Ser Gly Tyr Glu Trp Ile
1835 1840 1845
Thr Glu Tyr Thr Gly Lys Thr Val Trp Phe Val Pro Ser Val Lys
1850 1855 1860
Met Gly Asn Glu Ile Ala Leu Cys Leu Gln Arg Ala Gly Lys Lys
1865 1870 1875
Val Val Gln Leu Asn Arg Lys Ser Tyr Glu Thr Glu Tyr Pro Lys
1880 1885 1890
Cys Lys Asn Asp Asp Trp Asp Phe Val Ile Thr Thr Asp Ile Ser
1895 1900 1905
Glu Met Gly Ala Asn Phe Lys Ala Ser Arg Val Ile Asp Ser Arg
1910 1915 1920
Lys Ser Val Lys Pro Thr Ile Ile Thr Glu Gly Glu Gly Arg Val
1925 1930 1935
Ile Leu Gly Glu Pro Ser Ala Val Thr Ala Ala Ser Ala Ala Gln
1940 1945 1950
Arg Arg Gly Arg Ile Gly Arg Asn Pro Ser Gln Val Gly Asp Glu
1955 1960 1965
Tyr Cys Tyr Gly Gly His Thr Asn Glu Asp Asp Ser Asn Phe Ala
1970 1975 1980
His Trp Thr Glu Ala Arg Ile Met Leu Asp Asn Ile Asn Met Pro
1985 1990 1995
Asn Gly Leu Ile Ala Gln Phe Tyr Gln Pro Glu Arg Glu Lys Val
2000 2005 2010
Tyr Thr Met Asp Gly Glu Tyr Arg Leu Arg Gly Glu Glu Arg Lys
2015 2020 2025
Asn Phe Leu Glu Leu Leu Arg Thr Ala Asp Leu Pro Val Trp Leu
2030 2035 2040
Ala Tyr Lys Val Ala Ala Ala Gly Val Ser Tyr His Asp Arg Arg
2045 2050 2055
Trp Cys Phe Asp Gly Pro Arg Thr Asn Thr Ile Leu Glu Asp Asn
2060 2065 2070
Asn Glu Val Glu Val Ile Thr Lys Leu Gly Glu Arg Lys Ile Leu
2075 2080 2085
Arg Pro Arg Trp Ile Asp Ala Arg Val Tyr Ser Asp His Gln Ala
2090 2095 2100
Leu Lys Ala Phe Lys Asp Phe Ala Ser Gly Lys Arg Ser Gln Ile
2105 2110 2115
Gly Leu Ile Glu Val Leu Gly Lys Met Pro Glu His Phe Met Gly
2120 2125 2130
Lys Thr Trp Glu Ala Leu Asp Thr Met Tyr Val Val Ala Thr Ala
2135 2140 2145
Glu Lys Gly Gly Arg Ala His Arg Met Ala Leu Glu Glu Leu Pro
2150 2155 2160
Asp Ala Leu Gln Thr Ile Ala Leu Ile Ala Leu Leu Ser Val Met
2165 2170 2175
Thr Met Gly Val Phe Phe Leu Leu Met Gln Arg Lys Gly Ile Gly
2180 2185 2190
Lys Ile Gly Leu Gly Gly Ala Val Leu Gly Val Ala Thr Phe Phe
2195 2200 2205
Cys Trp Met Ala Glu Val Pro Gly Thr Lys Ile Ala Gly Met Leu
2210 2215 2220
Leu Leu Ser Leu Leu Leu Met Ile Val Leu Ile Pro Glu Pro Glu
2225 2230 2235
Lys Gln Arg Ser Gln Thr Asp Asn Gln Leu Ala Val Phe Leu Ile
2240 2245 2250
Cys Val Met Thr Leu Val Ser Ala Val Ala Ala Asn Glu Met Gly
2255 2260 2265
Trp Leu Asp Lys Thr Lys Ser Asp Ile Ser Ser Leu Phe Gly Gln
2270 2275 2280
Arg Ile Glu Val Lys Glu Asn Phe Ser Met Gly Glu Phe Leu Leu
2285 2290 2295
Asp Leu Arg Pro Ala Thr Ala Trp Ser Leu Tyr Ala Val Thr Thr
2300 2305 2310
Ala Val Leu Thr Pro Leu Leu Lys His Leu Ile Thr Ser Asp Tyr
2315 2320 2325
Ile Asn Thr Ser Leu Thr Ser Ile Asn Val Gln Ala Ser Ala Leu
2330 2335 2340
Phe Thr Leu Ala Arg Gly Phe Pro Phe Val Asp Val Gly Val Ser
2345 2350 2355
Ala Leu Leu Leu Ala Ala Gly Cys Trp Gly Gln Val Thr Leu Thr
2360 2365 2370
Val Thr Val Thr Ala Ala Thr Leu Leu Phe Cys His Tyr Ala Tyr
2375 2380 2385
Met Val Pro Gly Trp Gln Ala Glu Ala Met Arg Ser Ala Gln Arg
2390 2395 2400
Arg Thr Ala Ala Gly Ile Met Lys Asn Ala Val Val Asp Gly Ile
2405 2410 2415
Val Ala Thr Asp Val Pro Glu Leu Glu Arg Thr Thr Pro Ile Met
2420 2425 2430
Gln Lys Lys Val Gly Gln Ile Met Leu Ile Leu Val Ser Leu Ala
2435 2440 2445
Ala Val Val Val Asn Pro Ser Val Lys Thr Val Arg Glu Ala Gly
2450 2455 2460
Ile Leu Ile Thr Ala Ala Ala Val Thr Leu Trp Glu Asn Gly Ala
2465 2470 2475
Ser Ser Val Trp Asn Ala Thr Thr Ala Ile Gly Leu Cys His Ile
2480 2485 2490
Met Arg Gly Gly Trp Leu Ser Cys Leu Ser Ile Thr Trp Thr Leu
2495 2500 2505
Ile Lys Asn Met Glu Lys Pro Gly Leu Lys Arg Gly Gly Ala Lys
2510 2515 2520
Gly Arg Thr Leu Gly Glu Val Trp Lys Glu Arg Leu Asn Gln Met
2525 2530 2535
Thr Lys Glu Glu Phe Thr Arg Tyr Arg Lys Glu Ala Ile Ile Glu
2540 2545 2550
Val Asp Arg Ser Ala Ala Lys His Ala Arg Lys Glu Gly Asn Val
2555 2560 2565
Thr Gly Gly His Pro Val Ser Arg Gly Thr Ala Lys Leu Arg Trp
2570 2575 2580
Leu Val Glu Arg Arg Phe Leu Glu Pro Val Gly Lys Val Ile Asp
2585 2590 2595
Leu Gly Cys Gly Arg Gly Gly Trp Cys Tyr Tyr Met Ala Thr Gln
2600 2605 2610
Lys Arg Val Gln Glu Val Arg Gly Tyr Thr Lys Gly Gly Pro Gly
2615 2620 2625
His Glu Glu Pro Gln Leu Val Gln Ser Tyr Gly Trp Asn Ile Val
2630 2635 2640
Thr Met Lys Ser Gly Val Asp Val Phe Tyr Arg Pro Ser Glu Cys
2645 2650 2655
Cys Asp Thr Leu Leu Cys Asp Ile Gly Glu Ser Ser Ser Ser Ala
2660 2665 2670
Glu Val Glu Glu His Arg Thr Ile Arg Val Leu Glu Met Val Glu
2675 2680 2685
Asp Trp Leu His Arg Gly Pro Arg Glu Phe Cys Val Lys Val Leu
2690 2695 2700
Cys Pro Tyr Met Pro Lys Val Ile Glu Lys Met Glu Leu Leu Gln
2705 2710 2715
Arg Arg Tyr Gly Gly Gly Leu Val Arg Asn Pro Leu Ser Arg Asn
2720 2725 2730
Ser Thr His Glu Met Tyr Trp Val Ser Arg Ala Ser Gly Asn Val
2735 2740 2745
Val His Ser Val Asn Met Thr Ser Gln Val Leu Leu Gly Arg Met
2750 2755 2760
Glu Lys Arg Thr Trp Lys Gly Pro Gln Tyr Glu Glu Asp Val Asn
2765 2770 2775
Leu Gly Ser Gly Thr Arg Ala Val Gly Lys Pro Leu Leu Asn Ser
2780 2785 2790
Asp Thr Ser Lys Ile Lys Asn Arg Ile Glu Arg Leu Arg Arg Glu
2795 2800 2805
Tyr Ser Ser Thr Trp His His Asp Glu Asn His Pro Tyr Arg Thr
2810 2815 2820
Trp Asn Tyr His Gly Ser Tyr Asp Val Lys Pro Thr Gly Ser Ala
2825 2830 2835
Ser Ser Leu Val Asn Gly Val Val Arg Leu Leu Ser Lys Pro Trp
2840 2845 2850
Asp Thr Ile Thr Asn Val Thr Thr Met Ala Met Thr Asp Thr Thr
2855 2860 2865
Pro Phe Gly Gln Gln Arg Val Phe Lys Glu Lys Val Asp Thr Lys
2870 2875 2880
Ala Pro Glu Pro Pro Glu Gly Val Lys Tyr Val Leu Asn Glu Thr
2885 2890 2895
Thr Asn Trp Leu Trp Ala Phe Leu Ala Arg Glu Lys Arg Pro Arg
2900 2905 2910
Met Cys Ser Arg Glu Glu Phe Ile Arg Lys Val Asn Ser Asn Ala
2915 2920 2925
Ala Leu Gly Ala Met Phe Glu Glu Gln Asn Gln Trp Arg Ser Ala
2930 2935 2940
Arg Glu Ala Val Glu Asp Pro Lys Phe Trp Glu Met Val Asp Glu
2945 2950 2955
Glu Arg Glu Ala His Leu Arg Gly Glu Cys His Thr Cys Ile Tyr
2960 2965 2970
Asn Met Met Gly Lys Arg Glu Lys Lys Pro Gly Glu Phe Gly Lys
2975 2980 2985
Ala Lys Gly Ser Arg Ala Ile Trp Phe Met Trp Leu Gly Ala Arg
2990 2995 3000
Phe Leu Glu Phe Glu Ala Leu Gly Phe Leu Asn Glu Asp His Trp
3005 3010 3015
Leu Gly Arg Lys Asn Ser Gly Gly Gly Val Glu Gly Leu Gly Leu
3020 3025 3030
Gln Lys Leu Gly Tyr Ile Leu Arg Glu Val Gly Thr Arg Pro Gly
3035 3040 3045
Gly Lys Ile Tyr Ala Asp Asp Thr Ala Gly Trp Asp Thr Arg Ile
3050 3055 3060
Thr Arg Ala Asp Leu Glu Asn Glu Ala Lys Val Leu Glu Leu Leu
3065 3070 3075
Asp Gly Glu His Arg Arg Leu Ala Arg Ala Ile Ile Glu Leu Thr
3080 3085 3090
Tyr Arg His Lys Val Val Lys Val Met Arg Pro Ala Ala Asp Gly
3095 3100 3105
Arg Thr Val Met Asp Val Ile Ser Arg Glu Asp Gln Arg Gly Ser
3110 3115 3120
Gly Gln Val Val Thr Tyr Ala Leu Asn Thr Phe Thr Asn Leu Ala
3125 3130 3135
Val Gln Leu Val Arg Met Met Glu Gly Glu Gly Val Ile Gly Pro
3140 3145 3150
Asp Asp Val Glu Lys Leu Thr Lys Gly Lys Gly Pro Lys Val Arg
3155 3160 3165
Thr Trp Leu Phe Glu Asn Gly Glu Glu Arg Leu Ser Arg Met Ala
3170 3175 3180
Val Ser Gly Asp Asp Cys Val Val Lys Pro Leu Asp Asp Arg Phe
3185 3190 3195
Ala Thr Ser Leu His Phe Leu Asn Ala Met Ser Lys Val Arg Lys
3200 3205 3210
Asp Ile Gln Glu Trp Lys Pro Ser Thr Gly Trp Tyr Asp Trp Gln
3215 3220 3225
Gln Val Pro Phe Cys Ser Asn His Phe Thr Glu Leu Ile Met Lys
3230 3235 3240
Asp Gly Arg Thr Leu Val Val Pro Cys Arg Gly Gln Asp Glu Leu
3245 3250 3255
Val Gly Arg Ala Arg Ile Ser Pro Gly Ala Gly Trp Asn Val Arg
3260 3265 3270
Asp Thr Ala Cys Leu Ala Lys Ser Tyr Ala Gln Met Trp Leu Leu
3275 3280 3285
Leu Tyr Phe His Arg Arg Asp Leu Arg Leu Met Ala Asn Ala Ile
3290 3295 3300
Cys Ser Ala Val Pro Val Asn Trp Val Pro Thr Gly Arg Thr Thr
3305 3310 3315
Trp Ser Ile His Ala Gly Gly Glu Trp Met Thr Thr Glu Asp Met
3320 3325 3330
Leu Glu Val Trp Asn Arg Val Trp Ile Glu Glu Asn Glu Trp Met
3335 3340 3345
Glu Asp Lys Thr Pro Val Glu Lys Trp Ser Asp Val Pro Tyr Ser
3350 3355 3360
Gly Lys Arg Glu Asp Ile Trp Cys Gly Ser Leu Ile Gly Thr Arg
3365 3370 3375
Ala Arg Ala Thr Trp Ala Glu Asn Ile Gln Val Ala Ile Asn Gln
3380 3385 3390
Val Arg Ala Ile Ile Gly Asp Glu Lys Tyr Val Asp Tyr Met Ser
3395 3400 3405
Ser Leu Lys Arg Tyr Glu Asp Thr Thr Leu Val Glu Asp Thr Val
3410 3415 3420
Leu
<210> 19
<211> 10996
<212> DNA
<213> 人工序列
<220>
<223> 具有 C107 Thr 到 Pro 突变的WN/DEN4嵌合体
<220>
<221> CDS
<222> (97)..(10365)
<400> 19
agtagttcgc ctgtgtgagc tgacaaactt agtagtgttt gtgaggatta acaacaatta 60
acacagtgcg agctgtttct tagcacgaag atctcg atg tct aag aaa cca gga 114
Met Ser Lys Lys Pro Gly
1 5
ggg ccc ggc aag agc cgg gct gtc aat atg cta aaa cgc gga atg ccc 162
Gly Pro Gly Lys Ser Arg Ala Val Asn Met Leu Lys Arg Gly Met Pro
10 15 20
cgc gtg ttg tcc ttg att gga ctg aag agg gct atg ttg agc ctg atc 210
Arg Val Leu Ser Leu Ile Gly Leu Lys Arg Ala Met Leu Ser Leu Ile
25 30 35
gac ggc aag ggg cca ata cga ttt gtg ttg gct ctc ttg gcg ttc ttc 258
Asp Gly Lys Gly Pro Ile Arg Phe Val Leu Ala Leu Leu Ala Phe Phe
40 45 50
agg ttc aca gca att gct ccg acc cga gca gtg ctg gat cga tgg aga 306
Arg Phe Thr Ala Ile Ala Pro Thr Arg Ala Val Leu Asp Arg Trp Arg
55 60 65 70
ggt gtg aac aaa caa aca gcg atg aaa cac ctt ctg agt ttt aag aag 354
Gly Val Asn Lys Gln Thr Ala Met Lys His Leu Leu Ser Phe Lys Lys
75 80 85
gaa cta ggg acc ttg acc agt gct atc aat cgg cgg agc tca aaa caa 402
Glu Leu Gly Thr Leu Thr Ser Ala Ile Asn Arg Arg Ser Ser Lys Gln
90 95 100
aag aaa agg tca ccg ata aca ttg ctg tgc ttg att ccc acc gta atg 450
Lys Lys Arg Ser Pro Ile Thr Leu Leu Cys Leu Ile Pro Thr Val Met
105 110 115
gcg ttt cac ttg tca aca aga gat ggc gaa ccc ctc atg ata gtg gca 498
Ala Phe His Leu Ser Thr Arg Asp Gly Glu Pro Leu Met Ile Val Ala
120 125 130
aaa cat gaa agg ggg aga cct ctc ctg ttt aag aca aca gag ggg atc 546
Lys His Glu Arg Gly Arg Pro Leu Leu Phe Lys Thr Thr Glu Gly Ile
135 140 145 150
aac aaa tgc act ctc att gcc atg gac ttg ggt gaa atg tgt gag gac 594
Asn Lys Cys Thr Leu Ile Ala Met Asp Leu Gly Glu Met Cys Glu Asp
155 160 165
act gtc acg tac aaa tgc ccc tta ctg gtc aat acc gaa cct gaa gac 642
Thr Val Thr Tyr Lys Cys Pro Leu Leu Val Asn Thr Glu Pro Glu Asp
170 175 180
att gat tgc tgg tgc aat ctc acg tct acc tgg gtc atg tat ggg aca 690
Ile Asp Cys Trp Cys Asn Leu Thr Ser Thr Trp Val Met Tyr Gly Thr
185 190 195
tgc acc cag agc gga gaa cgg aga cga gag aag cgc tca gta gct tta 738
Cys Thr Gln Ser Gly Glu Arg Arg Arg Glu Lys Arg Ser Val Ala Leu
200 205 210
aca cca cat tca gga atg gga ttg gaa aca aga gct gag aca tgg atg 786
Thr Pro His Ser Gly Met Gly Leu Glu Thr Arg Ala Glu Thr Trp Met
215 220 225 230
tca tcg gaa ggg gct tgg aag cat gct cag aga gta gag agc tgg ata 834
Ser Ser Glu Gly Ala Trp Lys His Ala Gln Arg Val Glu Ser Trp Ile
235 240 245
ctc aga aac cca gga ttc gcg ctc ttg gca gga ttt atg gct tat atg 882
Leu Arg Asn Pro Gly Phe Ala Leu Leu Ala Gly Phe Met Ala Tyr Met
250 255 260
att ggg caa aca gga atc cag cga act gtc ttc ttt gtc cta atg atg 930
Ile Gly Gln Thr Gly Ile Gln Arg Thr Val Phe Phe Val Leu Met Met
265 270 275
ctg gtc gcc cca tcc tac gga atg cga tgc gta gga gta ggg aac aga 978
Leu Val Ala Pro Ser Tyr Gly Met Arg Cys Val Gly Val Gly Asn Arg
280 285 290
gac ttt gtg gaa gga gtc tca ggt gga gca tgg gtc gat ctg gtg cta 1026
Asp Phe Val Glu Gly Val Ser Gly Gly Ala Trp Val Asp Leu Val Leu
295 300 305 310
gaa cat gga gga tgc gtc aca acc atg gcc cag gga aaa cca acc ttg 1074
Glu His Gly Gly Cys Val Thr Thr Met Ala Gln Gly Lys Pro Thr Leu
315 320 325
gat ttt gaa ctg act aag aca aca gcc aag gaa gtg gct ctg tta aga 1122
Asp Phe Glu Leu Thr Lys Thr Thr Ala Lys Glu Val Ala Leu Leu Arg
330 335 340
acc tat tgc att gaa gcc tca ata tca aac ata acc acg gca aca aga 1170
Thr Tyr Cys Ile Glu Ala Ser Ile Ser Asn Ile Thr Thr Ala Thr Arg
345 350 355
tgt cca acg caa gga gag cct tat cta aaa gag gaa caa gac caa cag 1218
Cys Pro Thr Gln Gly Glu Pro Tyr Leu Lys Glu Glu Gln Asp Gln Gln
360 365 370
tac att tgc cgg aga gat gtg gta gac aga ggg tgg ggc aat ggc tgt 1266
Tyr Ile Cys Arg Arg Asp Val Val Asp Arg Gly Trp Gly Asn Gly Cys
375 380 385 390
ggc ttg ttt gga aaa gga gga gtt gtg aca tgt gcg aag ttt tca tgt 1314
Gly Leu Phe Gly Lys Gly Gly Val Val Thr Cys Ala Lys Phe Ser Cys
395 400 405
tcg ggg aag ata aca ggc aat ttg gtc caa att gag aac ctt gaa tac 1362
Ser Gly Lys Ile Thr Gly Asn Leu Val Gln Ile Glu Asn Leu Glu Tyr
410 415 420
aca gtg gtt gta aca gtc cac aat gga gac acc cat gca gta gga aat 1410
Thr Val Val Val Thr Val His Asn Gly Asp Thr His Ala Val Gly Asn
425 430 435
gac aca tcc aat cat gga gtt aca gcc acg ata act ccc agg tca cca 1458
Asp Thr Ser Asn His Gly Val Thr Ala Thr Ile Thr Pro Arg Ser Pro
440 445 450
tcg gtg gaa gtc aaa ttg ccg gac tat gga gaa cta aca ctc gat tgt 1506
Ser Val Glu Val Lys Leu Pro Asp Tyr Gly Glu Leu Thr Leu Asp Cys
455 460 465 470
gaa ccc agg tct gga att gac ttt aat gag atg att ctg atg aaa atg 1554
Glu Pro Arg Ser Gly Ile Asp Phe Asn Glu Met Ile Leu Met Lys Met
475 480 485
aaa aag aaa aca tgg ctt gtg cat aag caa tgg ttt ttg gat cta cct 1602
Lys Lys Lys Thr Trp Leu Val His Lys Gln Trp Phe Leu Asp Leu Pro
490 495 500
cta cca tgg aca gca gga gca gac aca tca gag gtt cac tgg aat tac 1650
Leu Pro Trp Thr Ala Gly Ala Asp Thr Ser Glu Val His Trp Asn Tyr
505 510 515
aaa gag aga atg gtg aca ttt aag gtt cct cat gcc aag aga cag gat 1698
Lys Glu Arg Met Val Thr Phe Lys Val Pro His Ala Lys Arg Gln Asp
520 525 530
gtg aca gtg ctg gga tct cag gaa gga gcc atg cat tct gcc ctc gct 1746
Val Thr Val Leu Gly Ser Gln Glu Gly Ala Met His Ser Ala Leu Ala
535 540 545 550
gga gcc aca gaa gtg gac tcc ggt gat gga aat cac atg ttt gca gga 1794
Gly Ala Thr Glu Val Asp Ser Gly Asp Gly Asn His Met Phe Ala Gly
555 560 565
cat ctc aag tgc aaa gtc cgt atg gag aaa ttg aga atc aag gga atg 1842
His Leu Lys Cys Lys Val Arg Met Glu Lys Leu Arg Ile Lys Gly Met
570 575 580
tca tac acg atg tgt tca gga aag ttc tca att gac aaa gag atg gca 1890
Ser Tyr Thr Met Cys Ser Gly Lys Phe Ser Ile Asp Lys Glu Met Ala
585 590 595
gaa aca cag cat ggg aca aca gtg gtg aaa gtc aag tat gaa ggt gct 1938
Glu Thr Gln His Gly Thr Thr Val Val Lys Val Lys Tyr Glu Gly Ala
600 605 610
gga gct ccg tgt aaa gtc ccc ata gag ata aga gat gtg aac aag gaa 1986
Gly Ala Pro Cys Lys Val Pro Ile Glu Ile Arg Asp Val Asn Lys Glu
615 620 625 630
aaa gtg gtt ggg cgt atc atc tca tcc acc cct ttg gct gag aat acc 2034
Lys Val Val Gly Arg Ile Ile Ser Ser Thr Pro Leu Ala Glu Asn Thr
635 640 645
aac agt gca acc aac ata gag tta gaa ccc ccc ttt ggg gac agc tac 2082
Asn Ser Ala Thr Asn Ile Glu Leu Glu Pro Pro Phe Gly Asp Ser Tyr
650 655 660
ata gtg ata ggt gtt gga aac agt gca tta aca ctc cat tgg ttc agg 2130
Ile Val Ile Gly Val Gly Asn Ser Ala Leu Thr Leu His Trp Phe Arg
665 670 675
aaa ggg agt tcc att ggc aag atg ttt gag tcc aca tac aga ggt gca 2178
Lys Gly Ser Ser Ile Gly Lys Met Phe Glu Ser Thr Tyr Arg Gly Ala
680 685 690
aaa cga atg gcc att cta ggt gaa aca gct tgg gat ttt ggt tcc gtt 2226
Lys Arg Met Ala Ile Leu Gly Glu Thr Ala Trp Asp Phe Gly Ser Val
695 700 705 710
ggt gga ctg ttc aca tca ttg gga aag gct gtg cac cag gtt ttt gga 2274
Gly Gly Leu Phe Thr Ser Leu Gly Lys Ala Val His Gln Val Phe Gly
715 720 725
agt gtg tat aca acc atg ttt gga gga gtc tca tgg atg att aga atc 2322
Ser Val Tyr Thr Thr Met Phe Gly Gly Val Ser Trp Met Ile Arg Ile
730 735 740
cta att ggg ttc cta gtg ttg tgg att ggc acg aac tca agg aac act 2370
Leu Ile Gly Phe Leu Val Leu Trp Ile Gly Thr Asn Ser Arg Asn Thr
745 750 755
tca atg gct atg acg tgc ata gct gtt gga gga atc act ctg ttt ctg 2418
Ser Met Ala Met Thr Cys Ile Ala Val Gly Gly Ile Thr Leu Phe Leu
760 765 770
ggc ttc aca gtt caa gca gac tcc gga tgt gcc ata gac atc agc cgg 2466
Gly Phe Thr Val Gln Ala Asp Ser Gly Cys Ala Ile Asp Ile Ser Arg
775 780 785 790
caa gag ctg aga tgt gga agt gga gtg ttc ata cac aat gat gtg gag 2514
Gln Glu Leu Arg Cys Gly Ser Gly Val Phe Ile His Asn Asp Val Glu
795 800 805
gct tgg atg gac cgg tac aag tat tac cct gaa acg cca caa ggc cta 2562
Ala Trp Met Asp Arg Tyr Lys Tyr Tyr Pro Glu Thr Pro Gln Gly Leu
810 815 820
gcc aag atc att cag aaa gct cat aag gaa gga gtg tgc ggt cta cga 2610
Ala Lys Ile Ile Gln Lys Ala His Lys Glu Gly Val Cys Gly Leu Arg
825 830 835
tca gtt tcc aga ctg gag cat caa atg tgg gaa gca gtg aag gac gag 2658
Ser Val Ser Arg Leu Glu His Gln Met Trp Glu Ala Val Lys Asp Glu
840 845 850
ctg aac act ctt ttg aag gag aat ggt gtg gac ctt agt gtc gtg gtt 2706
Leu Asn Thr Leu Leu Lys Glu Asn Gly Val Asp Leu Ser Val Val Val
855 860 865 870
gag aaa cag gag gga atg tac aag tca gca cct aaa cgc ctc acc gcc 2754
Glu Lys Gln Glu Gly Met Tyr Lys Ser Ala Pro Lys Arg Leu Thr Ala
875 880 885
acc acg gaa aaa ttg gaa att ggc tgg aag gcc tgg gga aag agt att 2802
Thr Thr Glu Lys Leu Glu Ile Gly Trp Lys Ala Trp Gly Lys Ser Ile
890 895 900
tta ttt gca cca gaa ctc gcc aac aac acc ttt gtg gtt gat ggt ccg 2850
Leu Phe Ala Pro Glu Leu Ala Asn Asn Thr Phe Val Val Asp Gly Pro
905 910 915
gag acc aag gaa tgt ccg act cag aat cgc gct tgg aat agc tta gaa 2898
Glu Thr Lys Glu Cys Pro Thr Gln Asn Arg Ala Trp Asn Ser Leu Glu
920 925 930
gtg gag gat ttt gga ttt ggt ctc acc agc act cgg atg ttc ctg aag 2946
Val Glu Asp Phe Gly Phe Gly Leu Thr Ser Thr Arg Met Phe Leu Lys
935 940 945 950
gtc aga gag agc aac aca act gaa tgt gac tcg aag atc att gga acg 2994
Val Arg Glu Ser Asn Thr Thr Glu Cys Asp Ser Lys Ile Ile Gly Thr
955 960 965
gct gtc aag aac aac ttg gcg atc cac agt gac ctg tcc tat tgg att 3042
Ala Val Lys Asn Asn Leu Ala Ile His Ser Asp Leu Ser Tyr Trp Ile
970 975 980
gaa agc agg ctc aat gat acg tgg aag ctt gaa agg gca gtt ctg ggt 3090
Glu Ser Arg Leu Asn Asp Thr Trp Lys Leu Glu Arg Ala Val Leu Gly
985 990 995
gaa gtc aaa tca tgt acg tgg cct gag acg cat acc ttg tgg ggc 3135
Glu Val Lys Ser Cys Thr Trp Pro Glu Thr His Thr Leu Trp Gly
1000 1005 1010
gat gga atc ctt gag agt gac ttg ata ata cca gtc aca ctg gcg 3180
Asp Gly Ile Leu Glu Ser Asp Leu Ile Ile Pro Val Thr Leu Ala
1015 1020 1025
gga cca cga agc aat cac aat cgg aga cct ggg tac aag aca caa 3225
Gly Pro Arg Ser Asn His Asn Arg Arg Pro Gly Tyr Lys Thr Gln
1030 1035 1040
aac cag ggc cca tgg gac gaa ggc cgg gta gag att gac ttc gat 3270
Asn Gln Gly Pro Trp Asp Glu Gly Arg Val Glu Ile Asp Phe Asp
1045 1050 1055
tac tgc cca gga act acg gtc acc ctg agt gag agc tgc gga cac 3315
Tyr Cys Pro Gly Thr Thr Val Thr Leu Ser Glu Ser Cys Gly His
1060 1065 1070
cgt gga cct gcc act cgc acc acc aca gag agc gga aag ttg ata 3360
Arg Gly Pro Ala Thr Arg Thr Thr Thr Glu Ser Gly Lys Leu Ile
1075 1080 1085
aca gat tgg tgc tgc agg agc tgc acc tta cca cca ctg cgc tac 3405
Thr Asp Trp Cys Cys Arg Ser Cys Thr Leu Pro Pro Leu Arg Tyr
1090 1095 1100
caa act gac agc ggc tgt tgg tat ggt atg gag atc aga cca cag 3450
Gln Thr Asp Ser Gly Cys Trp Tyr Gly Met Glu Ile Arg Pro Gln
1105 1110 1115
aga cat gat gaa aag acc ctc gtg cag tca caa gtg aat gct tat 3495
Arg His Asp Glu Lys Thr Leu Val Gln Ser Gln Val Asn Ala Tyr
1120 1125 1130
aat gct gat atg att gac cct ttt cag ttg ggc ctt ctg gtc gtg 3540
Asn Ala Asp Met Ile Asp Pro Phe Gln Leu Gly Leu Leu Val Val
1135 1140 1145
ttc ttg gcc acc cag gag gtc ctt cgc aag agg tgg aca gcc aag 3585
Phe Leu Ala Thr Gln Glu Val Leu Arg Lys Arg Trp Thr Ala Lys
1150 1155 1160
atc agc atg cca gct ata ctg att gct ctg cta gtc ctg gtg ttt 3630
Ile Ser Met Pro Ala Ile Leu Ile Ala Leu Leu Val Leu Val Phe
1165 1170 1175
ggg ggc att act tac act gat gtg tta cgc tat gtc atc ttg gtg 3675
Gly Gly Ile Thr Tyr Thr Asp Val Leu Arg Tyr Val Ile Leu Val
1180 1185 1190
ggg gca gct ttc gca gaa tct aat tcg gga gga gac gtg gta cac 3720
Gly Ala Ala Phe Ala Glu Ser Asn Ser Gly Gly Asp Val Val His
1195 1200 1205
ttg gcg ctc atg gcg acc ttc aag ata caa cca gtg ttt atg gtg 3765
Leu Ala Leu Met Ala Thr Phe Lys Ile Gln Pro Val Phe Met Val
1210 1215 1220
gca tcg ttt ctc aaa gcg aga tgg acc aac cag gag aac att ttg 3810
Ala Ser Phe Leu Lys Ala Arg Trp Thr Asn Gln Glu Asn Ile Leu
1225 1230 1235
ttg atg ttg gcg gct gtt ttc ttt caa atg gct tat tac gat gcc 3855
Leu Met Leu Ala Ala Val Phe Phe Gln Met Ala Tyr Tyr Asp Ala
1240 1245 1250
cgc caa att ctg ctc tgg gag atc cct gat gtg ttg aat tca ctg 3900
Arg Gln Ile Leu Leu Trp Glu Ile Pro Asp Val Leu Asn Ser Leu
1255 1260 1265
gcg gta gct tgg atg ata ctg aga gcc ata aca ttc aca acg aca 3945
Ala Val Ala Trp Met Ile Leu Arg Ala Ile Thr Phe Thr Thr Thr
1270 1275 1280
tca aac gtg gtt gtt ccg ctg cta gcc ctg cta aca ccc ggg ctg 3990
Ser Asn Val Val Val Pro Leu Leu Ala Leu Leu Thr Pro Gly Leu
1285 1290 1295
aga tgc ttg aat ctg gat gtg tac agg ata ctg ctg ttg atg gtc 4035
Arg Cys Leu Asn Leu Asp Val Tyr Arg Ile Leu Leu Leu Met Val
1300 1305 1310
gga ata ggc agc ttg atc agg gag aag agg agt gca gct gca aaa 4080
Gly Ile Gly Ser Leu Ile Arg Glu Lys Arg Ser Ala Ala Ala Lys
1315 1320 1325
aag aaa gga gca agt ctg cta tgc ttg gct cta gcc tca aca gga 4125
Lys Lys Gly Ala Ser Leu Leu Cys Leu Ala Leu Ala Ser Thr Gly
1330 1335 1340
ctt ttc aac ccc atg atc ctt gct gct gga ctg att gca tgt gat 4170
Leu Phe Asn Pro Met Ile Leu Ala Ala Gly Leu Ile Ala Cys Asp
1345 1350 1355
ccc aac cgt aaa cgc gga tgg ccc gca act gaa gtg atg aca gct 4215
Pro Asn Arg Lys Arg Gly Trp Pro Ala Thr Glu Val Met Thr Ala
1360 1365 1370
gtc ggc cta atg ttt gcc atc gtc gga ggg ctg gca gag ctt gac 4260
Val Gly Leu Met Phe Ala Ile Val Gly Gly Leu Ala Glu Leu Asp
1375 1380 1385
att gac tcc atg gcc att cca atg act atc gcg ggg ctc atg ttt 4305
Ile Asp Ser Met Ala Ile Pro Met Thr Ile Ala Gly Leu Met Phe
1390 1395 1400
gct gct ttc gtg att tct ggg aaa tca aca gat atg tgg att gag 4350
Ala Ala Phe Val Ile Ser Gly Lys Ser Thr Asp Met Trp Ile Glu
1405 1410 1415
aga acg gcg gac att tcc tgg gaa agt gat gca gaa att aca ggc 4395
Arg Thr Ala Asp Ile Ser Trp Glu Ser Asp Ala Glu Ile Thr Gly
1420 1425 1430
tcg agc gaa aga gtt gat gtg cgg ctt gat gat gat gga aac ttc 4440
Ser Ser Glu Arg Val Asp Val Arg Leu Asp Asp Asp Gly Asn Phe
1435 1440 1445
cag ctc atg aat gat cca gga gca cct tgg aag ata tgg atg ctc 4485
Gln Leu Met Asn Asp Pro Gly Ala Pro Trp Lys Ile Trp Met Leu
1450 1455 1460
aga atg gtc tgt ctc gcg att agt gcg tac acc ccc tgg gca atc 4530
Arg Met Val Cys Leu Ala Ile Ser Ala Tyr Thr Pro Trp Ala Ile
1465 1470 1475
ttg ccc tca gta gtt gga ttt tgg ata act ctc caa tac aca aag 4575
Leu Pro Ser Val Val Gly Phe Trp Ile Thr Leu Gln Tyr Thr Lys
1480 1485 1490
aga gga ggc gtg ttg tgg gac act ccc tca cca aag gag tac aaa 4620
Arg Gly Gly Val Leu Trp Asp Thr Pro Ser Pro Lys Glu Tyr Lys
1495 1500 1505
aag ggg gac acg acc acc ggc gtc tac agg atc atg act cgt ggg 4665
Lys Gly Asp Thr Thr Thr Gly Val Tyr Arg Ile Met Thr Arg Gly
1510 1515 1520
ctg ctc ggc agt tat caa gca gga gcg ggc gtg atg gtt gaa ggt 4710
Leu Leu Gly Ser Tyr Gln Ala Gly Ala Gly Val Met Val Glu Gly
1525 1530 1535
gtt ttc cac acc ctt tgg cat aca aca aaa gga gcc gct ttg atg 4755
Val Phe His Thr Leu Trp His Thr Thr Lys Gly Ala Ala Leu Met
1540 1545 1550
agc gga gag ggc cgc ctg gac cca tac tgg ggc agt gtc aag gag 4800
Ser Gly Glu Gly Arg Leu Asp Pro Tyr Trp Gly Ser Val Lys Glu
1555 1560 1565
gat cga ctt tgt tac gga gga ccc tgg aaa ttg cag cac aag tgg 4845
Asp Arg Leu Cys Tyr Gly Gly Pro Trp Lys Leu Gln His Lys Trp
1570 1575 1580
aac ggg cag gat gag gtg cag atg att gtg gtg gaa cct ggc agg 4890
Asn Gly Gln Asp Glu Val Gln Met Ile Val Val Glu Pro Gly Arg
1585 1590 1595
aac gtt aag aac gtc cag acg aaa cca ggg gtg ttc aaa aca cct 4935
Asn Val Lys Asn Val Gln Thr Lys Pro Gly Val Phe Lys Thr Pro
1600 1605 1610
gaa gga gaa atc ggg gcc gtg act ttg gac ttc ccc act gga aca 4980
Glu Gly Glu Ile Gly Ala Val Thr Leu Asp Phe Pro Thr Gly Thr
1615 1620 1625
tca ggc tca cca ata gtg gac aaa aac ggt gat gtg att ggg ctt 5025
Ser Gly Ser Pro Ile Val Asp Lys Asn Gly Asp Val Ile Gly Leu
1630 1635 1640
tat ggc aat gga gtc ata atg ccc aac ggc tca tac ata agc gcg 5070
Tyr Gly Asn Gly Val Ile Met Pro Asn Gly Ser Tyr Ile Ser Ala
1645 1650 1655
ata gtg cag ggt gaa agg atg gat gag cca atc cca gcc gga ttc 5115
Ile Val Gln Gly Glu Arg Met Asp Glu Pro Ile Pro Ala Gly Phe
1660 1665 1670
gaa cct gag atg ctg agg aaa aaa cag atc act gta ctg gat ctc 5160
Glu Pro Glu Met Leu Arg Lys Lys Gln Ile Thr Val Leu Asp Leu
1675 1680 1685
cat ccc ggc gcc ggt aaa aca agg agg att ctg cca cag atc atc 5205
His Pro Gly Ala Gly Lys Thr Arg Arg Ile Leu Pro Gln Ile Ile
1690 1695 1700
aaa gag gcc ata aac aga aga ctg aga aca gcc gtg cta gca cca 5250
Lys Glu Ala Ile Asn Arg Arg Leu Arg Thr Ala Val Leu Ala Pro
1705 1710 1715
acc agg gtt gtg gct gct gag atg gct gaa gca ctg aga gga ctg 5295
Thr Arg Val Val Ala Ala Glu Met Ala Glu Ala Leu Arg Gly Leu
1720 1725 1730
ccc atc cgg tac cag aca tcc gca gtg ccc aga gaa cat aat gga 5340
Pro Ile Arg Tyr Gln Thr Ser Ala Val Pro Arg Glu His Asn Gly
1735 1740 1745
aat gag att gtt gat gtc atg tgt cat gct acc ctc acc cac agg 5385
Asn Glu Ile Val Asp Val Met Cys His Ala Thr Leu Thr His Arg
1750 1755 1760
ctg atg tct cct cac agg gtg ccg aac tac aac ctg ttc gtg atg 5430
Leu Met Ser Pro His Arg Val Pro Asn Tyr Asn Leu Phe Val Met
1765 1770 1775
gat gag gct cat ttc acc gac cca gct agc att gca gca aga ggt 5475
Asp Glu Ala His Phe Thr Asp Pro Ala Ser Ile Ala Ala Arg Gly
1780 1785 1790
tac att tcc aca aag gtc gag cta ggg gag gcg gcg gca ata ttc 5520
Tyr Ile Ser Thr Lys Val Glu Leu Gly Glu Ala Ala Ala Ile Phe
1795 1800 1805
atg aca gcc acc cca cca ggc act tca gat cca ttc cca gag tcc 5565
Met Thr Ala Thr Pro Pro Gly Thr Ser Asp Pro Phe Pro Glu Ser
1810 1815 1820
aat tca cca att tcc gac tta cag act gag atc ccg gat cga gct 5610
Asn Ser Pro Ile Ser Asp Leu Gln Thr Glu Ile Pro Asp Arg Ala
1825 1830 1835
tgg aac tct gga tac gaa tgg atc aca gaa tac acc ggg aag acg 5655
Trp Asn Ser Gly Tyr Glu Trp Ile Thr Glu Tyr Thr Gly Lys Thr
1840 1845 1850
gtt tgg ttt gtg cct agt gtc aag atg ggg aat gag att gcc ctt 5700
Val Trp Phe Val Pro Ser Val Lys Met Gly Asn Glu Ile Ala Leu
1855 1860 1865
tgc cta caa cgt gct gga aag aaa gta gtc caa ttg aac aga aag 5745
Cys Leu Gln Arg Ala Gly Lys Lys Val Val Gln Leu Asn Arg Lys
1870 1875 1880
tcg tac gag acg gag tac cca aaa tgt aag aac gat gat tgg gac 5790
Ser Tyr Glu Thr Glu Tyr Pro Lys Cys Lys Asn Asp Asp Trp Asp
1885 1890 1895
ttt gtt atc aca aca gac ata tct gaa atg ggg gct aac ttc aag 5835
Phe Val Ile Thr Thr Asp Ile Ser Glu Met Gly Ala Asn Phe Lys
1900 1905 1910
gcg agc agg gtg att gac agc cgg aag agt gtg aaa cca acc atc 5880
Ala Ser Arg Val Ile Asp Ser Arg Lys Ser Val Lys Pro Thr Ile
1915 1920 1925
ata aca gaa gga gaa ggg aga gtg atc ctg gga gaa cca tct gca 5925
Ile Thr Glu Gly Glu Gly Arg Val Ile Leu Gly Glu Pro Ser Ala
1930 1935 1940
gtg aca gca gct agt gcc gcc cag aga cgt gga cgt atc ggt aga 5970
Val Thr Ala Ala Ser Ala Ala Gln Arg Arg Gly Arg Ile Gly Arg
1945 1950 1955
aat ccg tcg caa gtt ggt gat gag tac tgt tat ggg ggg cac acg 6015
Asn Pro Ser Gln Val Gly Asp Glu Tyr Cys Tyr Gly Gly His Thr
1960 1965 1970
aat gaa gac gac tcg aac ttc gcc cat tgg act gag gca cga atc 6060
Asn Glu Asp Asp Ser Asn Phe Ala His Trp Thr Glu Ala Arg Ile
1975 1980 1985
atg ctg gac aac atc aac atg cca aac gga ctg atc gct caa ttc 6105
Met Leu Asp Asn Ile Asn Met Pro Asn Gly Leu Ile Ala Gln Phe
1990 1995 2000
tac caa cca gag cgt gag aag gta tat acc atg gat ggg gaa tac 6150
Tyr Gln Pro Glu Arg Glu Lys Val Tyr Thr Met Asp Gly Glu Tyr
2005 2010 2015
cgg ctc aga gga gaa gag aga aaa aac ttt ctg gaa ctg ttg agg 6195
Arg Leu Arg Gly Glu Glu Arg Lys Asn Phe Leu Glu Leu Leu Arg
2020 2025 2030
act gca gat ctg cca gtt tgg ctg gct tac aag gtt gca gcg gct 6240
Thr Ala Asp Leu Pro Val Trp Leu Ala Tyr Lys Val Ala Ala Ala
2035 2040 2045
gga gtg tca tac cac gac cgg agg tgg tgc ttt gat ggt cct agg 6285
Gly Val Ser Tyr His Asp Arg Arg Trp Cys Phe Asp Gly Pro Arg
2050 2055 2060
aca aac aca att tta gaa gac aac aac gaa gtg gaa gtc atc acg 6330
Thr Asn Thr Ile Leu Glu Asp Asn Asn Glu Val Glu Val Ile Thr
2065 2070 2075
aag ctt ggt gaa agg aag att ctg agg ccg cgc tgg att gac gcc 6375
Lys Leu Gly Glu Arg Lys Ile Leu Arg Pro Arg Trp Ile Asp Ala
2080 2085 2090
agg gtg tac tcg gat cac cag gca cta aag gcg ttc aag gac ttc 6420
Arg Val Tyr Ser Asp His Gln Ala Leu Lys Ala Phe Lys Asp Phe
2095 2100 2105
gcc tcg gga aaa cgt tct cag ata ggg ctc att gag gtt ctg gga 6465
Ala Ser Gly Lys Arg Ser Gln Ile Gly Leu Ile Glu Val Leu Gly
2110 2115 2120
aag atg cct gag cac ttc atg ggg aag aca tgg gaa gca ctt gac 6510
Lys Met Pro Glu His Phe Met Gly Lys Thr Trp Glu Ala Leu Asp
2125 2130 2135
acc atg tac gtt gtg gcc act gca gag aaa gga gga aga gct cac 6555
Thr Met Tyr Val Val Ala Thr Ala Glu Lys Gly Gly Arg Ala His
2140 2145 2150
aga atg gcc ctg gag gaa ctg cca gat gct ctt cag aca att gcc 6600
Arg Met Ala Leu Glu Glu Leu Pro Asp Ala Leu Gln Thr Ile Ala
2155 2160 2165
ttg att gcc tta ttg agt gtg atg acc atg gga gta ttc ttc ctc 6645
Leu Ile Ala Leu Leu Ser Val Met Thr Met Gly Val Phe Phe Leu
2170 2175 2180
ctc atg cag cgg aag ggc att gga aag ata ggt ttg gga ggc gct 6690
Leu Met Gln Arg Lys Gly Ile Gly Lys Ile Gly Leu Gly Gly Ala
2185 2190 2195
gtc ttg gga gtc gcg acc ttt ttc tgt tgg atg gct gaa gtt cca 6735
Val Leu Gly Val Ala Thr Phe Phe Cys Trp Met Ala Glu Val Pro
2200 2205 2210
gga acg aag atc gcc gga atg ttg ctg ctc tcc ctt ctc ttg atg 6780
Gly Thr Lys Ile Ala Gly Met Leu Leu Leu Ser Leu Leu Leu Met
2215 2220 2225
att gtg cta att cct gag cca gag aag caa cgt tcg cag aca gac 6825
Ile Val Leu Ile Pro Glu Pro Glu Lys Gln Arg Ser Gln Thr Asp
2230 2235 2240
aac cag cta gcc gtg ttc ctg att tgt gtc atg acc ctt gtg agc 6870
Asn Gln Leu Ala Val Phe Leu Ile Cys Val Met Thr Leu Val Ser
2245 2250 2255
gca gtg gca gcc aac gag atg ggt tgg cta gat aag acc aag agt 6915
Ala Val Ala Ala Asn Glu Met Gly Trp Leu Asp Lys Thr Lys Ser
2260 2265 2270
gac ata agc agt ttg ttt ggg caa aga att gag gtc aag gag aat 6960
Asp Ile Ser Ser Leu Phe Gly Gln Arg Ile Glu Val Lys Glu Asn
2275 2280 2285
ttc agc atg gga gag ttt ctt ttg gac ttg agg cct gca aca gcc 7005
Phe Ser Met Gly Glu Phe Leu Leu Asp Leu Arg Pro Ala Thr Ala
2290 2295 2300
tgg tca ctg tac gct gtg aca aca gcg gtc ctc act cca ctg cta 7050
Trp Ser Leu Tyr Ala Val Thr Thr Ala Val Leu Thr Pro Leu Leu
2305 2310 2315
aag cat ttg atc acg tca gat tac atc aac acc tca ttg acc tca 7095
Lys His Leu Ile Thr Ser Asp Tyr Ile Asn Thr Ser Leu Thr Ser
2320 2325 2330
ata aac gtt cag gca agt gca cta ttc aca ctc gcg cga ggc ttc 7140
Ile Asn Val Gln Ala Ser Ala Leu Phe Thr Leu Ala Arg Gly Phe
2335 2340 2345
ccc ttc gtc gat gtt gga gtg tcg gct ctc ctg cta gca gcc gga 7185
Pro Phe Val Asp Val Gly Val Ser Ala Leu Leu Leu Ala Ala Gly
2350 2355 2360
tgc tgg gga caa gtc acc ctc acc gtt acg gta aca gcg gca aca 7230
Cys Trp Gly Gln Val Thr Leu Thr Val Thr Val Thr Ala Ala Thr
2365 2370 2375
ctc ctt ttt tgc cac tat gcc tac atg gtt ccc ggt tgg caa gct 7275
Leu Leu Phe Cys His Tyr Ala Tyr Met Val Pro Gly Trp Gln Ala
2380 2385 2390
gag gca atg cgc tca gcc cag cgg cgg aca gcg gcc gga atc atg 7320
Glu Ala Met Arg Ser Ala Gln Arg Arg Thr Ala Ala Gly Ile Met
2395 2400 2405
aag aac gct gta gtg gat ggc atc gtg gcc acg gac gtc cca gaa 7365
Lys Asn Ala Val Val Asp Gly Ile Val Ala Thr Asp Val Pro Glu
2410 2415 2420
tta gag cgc acc aca ccc atc atg cag aag aaa gtt gga cag atc 7410
Leu Glu Arg Thr Thr Pro Ile Met Gln Lys Lys Val Gly Gln Ile
2425 2430 2435
atg ctg atc ttg gtg tct cta gct gca gta gta gtg aac ccg tct 7455
Met Leu Ile Leu Val Ser Leu Ala Ala Val Val Val Asn Pro Ser
2440 2445 2450
gtg aag aca gta cga gaa gcc gga att ttg atc acg gcc gca gcg 7500
Val Lys Thr Val Arg Glu Ala Gly Ile Leu Ile Thr Ala Ala Ala
2455 2460 2465
gtg acg ctt tgg gag aat gga gca agc tct gtt tgg aac gca aca 7545
Val Thr Leu Trp Glu Asn Gly Ala Ser Ser Val Trp Asn Ala Thr
2470 2475 2480
act gcc atc gga ctc tgc cac atc atg cgt ggg ggt tgg ttg tca 7590
Thr Ala Ile Gly Leu Cys His Ile Met Arg Gly Gly Trp Leu Ser
2485 2490 2495
tgt cta tcc ata aca tgg aca ctc ata aag aac atg gaa aaa cca 7635
Cys Leu Ser Ile Thr Trp Thr Leu Ile Lys Asn Met Glu Lys Pro
2500 2505 2510
gga cta aaa aga ggt ggg gca aaa gga cgc acc ttg gga gag gtt 7680
Gly Leu Lys Arg Gly Gly Ala Lys Gly Arg Thr Leu Gly Glu Val
2515 2520 2525
tgg aaa gaa aga ctc aac cag atg aca aaa gaa gag ttc act agg 7725
Trp Lys Glu Arg Leu Asn Gln Met Thr Lys Glu Glu Phe Thr Arg
2530 2535 2540
tac cgc aaa gag gcc atc atc gaa gtc gat cgc tca gcg gca aaa 7770
Tyr Arg Lys Glu Ala Ile Ile Glu Val Asp Arg Ser Ala Ala Lys
2545 2550 2555
cac gcc agg aaa gaa ggc aat gtc act gga ggg cat cca gtc tct 7815
His Ala Arg Lys Glu Gly Asn Val Thr Gly Gly His Pro Val Ser
2560 2565 2570
agg ggc aca gca aaa ctg aga tgg ctg gtc gaa cgg agg ttt ctc 7860
Arg Gly Thr Ala Lys Leu Arg Trp Leu Val Glu Arg Arg Phe Leu
2575 2580 2585
gaa ccg gtc gga aaa gtg att gac ctt gga tgt gga aga ggc ggt 7905
Glu Pro Val Gly Lys Val Ile Asp Leu Gly Cys Gly Arg Gly Gly
2590 2595 2600
tgg tgt tac tat atg gca acc caa aaa aga gtc caa gaa gtc aga 7950
Trp Cys Tyr Tyr Met Ala Thr Gln Lys Arg Val Gln Glu Val Arg
2605 2610 2615
ggg tac aca aag ggc ggt ccc gga cat gaa gag ccc caa cta gtg 7995
Gly Tyr Thr Lys Gly Gly Pro Gly His Glu Glu Pro Gln Leu Val
2620 2625 2630
caa agt tat gga tgg aac att gtc acc atg aag agt gga gtg gat 8040
Gln Ser Tyr Gly Trp Asn Ile Val Thr Met Lys Ser Gly Val Asp
2635 2640 2645
gtg ttc tac aga cct tct gag tgt tgt gac acc ctc ctt tgt gac 8085
Val Phe Tyr Arg Pro Ser Glu Cys Cys Asp Thr Leu Leu Cys Asp
2650 2655 2660
atc gga gag tcc tcg tca agt gct gag gtt gaa gag cat agg acg 8130
Ile Gly Glu Ser Ser Ser Ser Ala Glu Val Glu Glu His Arg Thr
2665 2670 2675
att cgg gtc ctt gaa atg gtt gag gac tgg ctg cac cga ggg cca 8175
Ile Arg Val Leu Glu Met Val Glu Asp Trp Leu His Arg Gly Pro
2680 2685 2690
agg gaa ttt tgc gtg aag gtg ctc tgc ccc tac atg ccg aaa gtc 8220
Arg Glu Phe Cys Val Lys Val Leu Cys Pro Tyr Met Pro Lys Val
2695 2700 2705
ata gag aag atg gag ctg ctc caa cgc cgg tat ggg ggg gga ctg 8265
Ile Glu Lys Met Glu Leu Leu Gln Arg Arg Tyr Gly Gly Gly Leu
2710 2715 2720
gtc aga aac cca ctc tca cgg aat tcc acg cac gag atg tat tgg 8310
Val Arg Asn Pro Leu Ser Arg Asn Ser Thr His Glu Met Tyr Trp
2725 2730 2735
gtg agt cga gct tca ggc aat gtg gta cat tca gtg aat atg acc 8355
Val Ser Arg Ala Ser Gly Asn Val Val His Ser Val Asn Met Thr
2740 2745 2750
agc cag gtg ctc cta gga aga atg gaa aaa agg acc tgg aag gga 8400
Ser Gln Val Leu Leu Gly Arg Met Glu Lys Arg Thr Trp Lys Gly
2755 2760 2765
ccc caa tac gag gaa gat gta aac ttg gga agt gga acc agg gcg 8445
Pro Gln Tyr Glu Glu Asp Val Asn Leu Gly Ser Gly Thr Arg Ala
2770 2775 2780
gtg gga aaa ccc ctg ctc aac tca gac acc agt aaa atc aag aac 8490
Val Gly Lys Pro Leu Leu Asn Ser Asp Thr Ser Lys Ile Lys Asn
2785 2790 2795
agg att gaa cga ctc agg cgt gag tac agt tcg acg tgg cac cac 8535
Arg Ile Glu Arg Leu Arg Arg Glu Tyr Ser Ser Thr Trp His His
2800 2805 2810
gat gag aac cac cca tat aga acc tgg aac tat cac ggc agt tat 8580
Asp Glu Asn His Pro Tyr Arg Thr Trp Asn Tyr His Gly Ser Tyr
2815 2820 2825
gat gtg aag ccc aca ggc tcc gcc agt tcg ctg gtc aat gga gtg 8625
Asp Val Lys Pro Thr Gly Ser Ala Ser Ser Leu Val Asn Gly Val
2830 2835 2840
gtc agg ctc ctc tca aaa cca tgg gac acc atc acg aat gtt acc 8670
Val Arg Leu Leu Ser Lys Pro Trp Asp Thr Ile Thr Asn Val Thr
2845 2850 2855
acc atg gcc atg act gac act act ccc ttc ggg cag cag cga gtg 8715
Thr Met Ala Met Thr Asp Thr Thr Pro Phe Gly Gln Gln Arg Val
2860 2865 2870
ttc aaa gag aag gtg gac acg aaa gct cct gaa ccg cca gaa gga 8760
Phe Lys Glu Lys Val Asp Thr Lys Ala Pro Glu Pro Pro Glu Gly
2875 2880 2885
gtg aag tac gtg ctc aac gag acc acc aac tgg ttg tgg gcg ttt 8805
Val Lys Tyr Val Leu Asn Glu Thr Thr Asn Trp Leu Trp Ala Phe
2890 2895 2900
ttg gcc aga gaa aaa cgt ccc aga atg tgc tct cga gag gaa ttc 8850
Leu Ala Arg Glu Lys Arg Pro Arg Met Cys Ser Arg Glu Glu Phe
2905 2910 2915
ata aga aag gtc aac agc aat gca gct ttg ggt gcc atg ttt gaa 8895
Ile Arg Lys Val Asn Ser Asn Ala Ala Leu Gly Ala Met Phe Glu
2920 2925 2930
gag cag aat caa tgg agg agc gcc aga gaa gca gtt gaa gat cca 8940
Glu Gln Asn Gln Trp Arg Ser Ala Arg Glu Ala Val Glu Asp Pro
2935 2940 2945
aaa ttt tgg gag atg gtg gat gag gag cgc gag gca cat ctg cgg 8985
Lys Phe Trp Glu Met Val Asp Glu Glu Arg Glu Ala His Leu Arg
2950 2955 2960
ggg gaa tgt cac act tgc att tac aac atg atg gga aag aga gag 9030
Gly Glu Cys His Thr Cys Ile Tyr Asn Met Met Gly Lys Arg Glu
2965 2970 2975
aaa aaa ccc gga gag ttc gga aag gcc aag gga agc aga gcc att 9075
Lys Lys Pro Gly Glu Phe Gly Lys Ala Lys Gly Ser Arg Ala Ile
2980 2985 2990
tgg ttc atg tgg ctc gga gct cgc ttt ctg gag ttc gag gct ctg 9120
Trp Phe Met Trp Leu Gly Ala Arg Phe Leu Glu Phe Glu Ala Leu
2995 3000 3005
ggt ttt ctc aat gaa gac cac tgg ctt gga aga aag aac tca gga 9165
Gly Phe Leu Asn Glu Asp His Trp Leu Gly Arg Lys Asn Ser Gly
3010 3015 3020
gga ggt gtc gag ggc ttg ggc ctc caa aaa ctg ggt tac atc ctg 9210
Gly Gly Val Glu Gly Leu Gly Leu Gln Lys Leu Gly Tyr Ile Leu
3025 3030 3035
cgt gaa gtt ggc acc cgg cct ggg ggc aag atc tat gct gat gac 9255
Arg Glu Val Gly Thr Arg Pro Gly Gly Lys Ile Tyr Ala Asp Asp
3040 3045 3050
aca gct ggc tgg gac acc cgc atc acg aga gct gac ttg gaa aat 9300
Thr Ala Gly Trp Asp Thr Arg Ile Thr Arg Ala Asp Leu Glu Asn
3055 3060 3065
gaa gct aag gtg ctt gag ctg ctt gat ggg gaa cat cgg cgt ctt 9345
Glu Ala Lys Val Leu Glu Leu Leu Asp Gly Glu His Arg Arg Leu
3070 3075 3080
gcc agg gcc atc att gag ctc acc tat cgt cac aaa gtt gtg aaa 9390
Ala Arg Ala Ile Ile Glu Leu Thr Tyr Arg His Lys Val Val Lys
3085 3090 3095
gtg atg cgc ccg gct gct gat gga aga acc gtc atg gat gtt atc 9435
Val Met Arg Pro Ala Ala Asp Gly Arg Thr Val Met Asp Val Ile
3100 3105 3110
tcc aga gaa gat cag agg ggg agt gga caa gtt gtc acc tac gcc 9480
Ser Arg Glu Asp Gln Arg Gly Ser Gly Gln Val Val Thr Tyr Ala
3115 3120 3125
cta aac act ttc acc aac ctg gcc gtc cag ctg gtg agg atg atg 9525
Leu Asn Thr Phe Thr Asn Leu Ala Val Gln Leu Val Arg Met Met
3130 3135 3140
gaa ggg gaa gga gtg att ggc cca gat gat gtg gag aaa ctc aca 9570
Glu Gly Glu Gly Val Ile Gly Pro Asp Asp Val Glu Lys Leu Thr
3145 3150 3155
aaa ggg aaa gga ccc aaa gtc agg acc tgg ctg ttt gag aat ggg 9615
Lys Gly Lys Gly Pro Lys Val Arg Thr Trp Leu Phe Glu Asn Gly
3160 3165 3170
gaa gaa aga ctc agc cgc atg gct gtc agt gga gat gac tgt gtg 9660
Glu Glu Arg Leu Ser Arg Met Ala Val Ser Gly Asp Asp Cys Val
3175 3180 3185
gta aag ccc ctg gac gat cgc ttt gcc acc tcg ctc cac ttc ctc 9705
Val Lys Pro Leu Asp Asp Arg Phe Ala Thr Ser Leu His Phe Leu
3190 3195 3200
aat gct atg tca aag gtt cgc aaa gac atc caa gag tgg aaa ccg 9750
Asn Ala Met Ser Lys Val Arg Lys Asp Ile Gln Glu Trp Lys Pro
3205 3210 3215
tca act gga tgg tat gat tgg cag cag gtt cca ttt tgc tca aac 9795
Ser Thr Gly Trp Tyr Asp Trp Gln Gln Val Pro Phe Cys Ser Asn
3220 3225 3230
cat ttc act gaa ttg atc atg aaa gat gga aga aca ctg gtg gtt 9840
His Phe Thr Glu Leu Ile Met Lys Asp Gly Arg Thr Leu Val Val
3235 3240 3245
cca tgc cga gga cag gat gaa ttg gta ggc aga gct cgc ata tct 9885
Pro Cys Arg Gly Gln Asp Glu Leu Val Gly Arg Ala Arg Ile Ser
3250 3255 3260
cca ggg gcc gga tgg aac gtc cgc gac act gct tgt ctg gct aag 9930
Pro Gly Ala Gly Trp Asn Val Arg Asp Thr Ala Cys Leu Ala Lys
3265 3270 3275
tct tat gcc cag atg tgg ctg ctt ctg tac ttc cac aga aga gac 9975
Ser Tyr Ala Gln Met Trp Leu Leu Leu Tyr Phe His Arg Arg Asp
3280 3285 3290
ctg cgg ctc atg gcc aac gcc att tgc tcc gct gtc cct gtg aat 10020
Leu Arg Leu Met Ala Asn Ala Ile Cys Ser Ala Val Pro Val Asn
3295 3300 3305
tgg gtc cct acc gga aga acc acg tgg tcc atc cat gca gga gga 10065
Trp Val Pro Thr Gly Arg Thr Thr Trp Ser Ile His Ala Gly Gly
3310 3315 3320
gag tgg atg aca aca gag gac atg ttg gag gtc tgg aac cgt gtt 10110
Glu Trp Met Thr Thr Glu Asp Met Leu Glu Val Trp Asn Arg Val
3325 3330 3335
tgg ata gag gag aat gaa tgg atg gaa gac aaa acc cca gtg gag 10155
Trp Ile Glu Glu Asn Glu Trp Met Glu Asp Lys Thr Pro Val Glu
3340 3345 3350
aaa tgg agt gac gtc cca tat tca gga aaa cga gag gac atc tgg 10200
Lys Trp Ser Asp Val Pro Tyr Ser Gly Lys Arg Glu Asp Ile Trp
3355 3360 3365
tgt ggc agc ctg att ggc aca aga gcc cga gcc acg tgg gca gaa 10245
Cys Gly Ser Leu Ile Gly Thr Arg Ala Arg Ala Thr Trp Ala Glu
3370 3375 3380
aac atc cag gtg gct atc aac caa gtc aga gca atc atc gga gat 10290
Asn Ile Gln Val Ala Ile Asn Gln Val Arg Ala Ile Ile Gly Asp
3385 3390 3395
gag aag tat gtg gat tac atg agt tca cta aag aga tat gaa gac 10335
Glu Lys Tyr Val Asp Tyr Met Ser Ser Leu Lys Arg Tyr Glu Asp
3400 3405 3410
aca act ttg gtt gag gac aca gta ctg tag atatttaatc aattgtaaat 10385
Thr Thr Leu Val Glu Asp Thr Val Leu
3415 3420
agacaatata agtatgcata aaagtgtagt tttatagtag tatttagtgg tgttagtgta10445
aatagttaag aaaattttga ggagaaagtc aggccgggaa gttcccgcca ccggaagttg10505
agtagacggt gctgcctgcg actcaacccc aggaggactg ggtgaacaaa gccgcgaagt10565
gatccatgta agccctcaga accgtctcgg aaggaggacc ccacatgttg taacttcaaa10625
gcccaatgtc agaccacgct acggcgtgct actctgcgga gagtgcagtc tgcgatagtg10685
ccccaggagg actgggttaa caaaggcaaa ccaacgcccc acgcggccct agccccggta10745
atggtgttaa ccagggcgaa aggactagag gttagaggag accccgcggt ttaaagtgca10805
cggcccagcc tggctgaagc tgtaggtcag gggaaggact agaggttagt ggagaccccg10865
tgccacaaaa caccacaaca aaacagcata ttgacacctg ggatagacta ggagatcttc10925
tgctctgcac aaccagccac acggcacagt gcgccgacaa tggtggctgg tggtgcgaga10985
acacaggatc t 10996
<210> 20
<211> 3422
<212> PRT
<213> 人工序列
<220>
<223> 合成的构建体
<400> 20
Met Ser Lys Lys Pro Gly Gly Pro Gly Lys Ser Arg Ala Val Asn Met
1 5 10 15
Leu Lys Arg Gly Met Pro Arg Val Leu Ser Leu Ile Gly Leu Lys Arg
20 25 30
Ala Met Leu Ser Leu Ile Asp Gly Lys Gly Pro Ile Arg Phe Val Leu
35 40 45
Ala Leu Leu Ala Phe Phe Arg Phe Thr Ala Ile Ala Pro Thr Arg Ala
50 55 60
Val Leu Asp Arg Trp Arg Gly Val Asn Lys Gln Thr Ala Met Lys His
65 70 75 80
Leu Leu Ser Phe Lys Lys Glu Leu Gly Thr Leu Thr Ser Ala Ile Asn
85 90 95
Arg Arg Ser Ser Lys Gln Lys Lys Arg Ser Pro Ile Thr Leu Leu Cys
100 105 110
Leu Ile Pro Thr Val Met Ala Phe His Leu Ser Thr Arg Asp Gly Glu
115 120 125
Pro Leu Met Ile Val Ala Lys His Glu Arg Gly Arg Pro Leu Leu Phe
130 135 140
Lys Thr Thr Glu Gly Ile Asn Lys Cys Thr Leu Ile Ala Met Asp Leu
145 150 155 160
Gly Glu Met Cys Glu Asp Thr Val Thr Tyr Lys Cys Pro Leu Leu Val
165 170 175
Asn Thr Glu Pro Glu Asp Ile Asp Cys Trp Cys Asn Leu Thr Ser Thr
180 185 190
Trp Val Met Tyr Gly Thr Cys Thr Gln Ser Gly Glu Arg Arg Arg Glu
195 200 205
Lys Arg Ser Val Ala Leu Thr Pro His Ser Gly Met Gly Leu Glu Thr
210 215 220
Arg Ala Glu Thr Trp Met Ser Ser Glu Gly Ala Trp Lys His Ala Gln
225 230 235 240
Arg Val Glu Ser Trp Ile Leu Arg Asn Pro Gly Phe Ala Leu Leu Ala
245 250 255
Gly Phe Met Ala Tyr Met Ile Gly Gln Thr Gly Ile Gln Arg Thr Val
260 265 270
Phe Phe Val Leu Met Met Leu Val Ala Pro Ser Tyr Gly Met Arg Cys
275 280 285
Val Gly Val Gly Asn Arg Asp Phe Val Glu Gly Val Ser Gly Gly Ala
290 295 300
Trp Val Asp Leu Val Leu Glu His Gly Gly Cys Val Thr Thr Met Ala
305 310 315 320
Gln Gly Lys Pro Thr Leu Asp Phe Glu Leu Thr Lys Thr Thr Ala Lys
325 330 335
Glu Val Ala Leu Leu Arg Thr Tyr Cys Ile Glu Ala Ser Ile Ser Asn
340 345 350
Ile Thr Thr Ala Thr Arg Cys Pro Thr Gln Gly Glu Pro Tyr Leu Lys
355 360 365
Glu Glu Gln Asp Gln Gln Tyr Ile Cys Arg Arg Asp Val Val Asp Arg
370 375 380
Gly Trp Gly Asn Gly Cys Gly Leu Phe Gly Lys Gly Gly Val Val Thr
385 390 395 400
Cys Ala Lys Phe Ser Cys Ser Gly Lys Ile Thr Gly Asn Leu Val Gln
405 410 415
Ile Glu Asn Leu Glu Tyr Thr Val Val Val Thr Val His Asn Gly Asp
420 425 430
Thr His Ala Val Gly Asn Asp Thr Ser Asn His Gly Val Thr Ala Thr
435 440 445
Ile Thr Pro Arg Ser Pro Ser Val Glu Val Lys Leu Pro Asp Tyr Gly
450 455 460
Glu Leu Thr Leu Asp Cys Glu Pro Arg Ser Gly Ile Asp Phe Asn Glu
465 470 475 480
Met Ile Leu Met Lys Met Lys Lys Lys Thr Trp Leu Val His Lys Gln
485 490 495
Trp Phe Leu Asp Leu Pro Leu Pro Trp Thr Ala Gly Ala Asp Thr Ser
500 505 510
Glu Val His Trp Asn Tyr Lys Glu Arg Met Val Thr Phe Lys Val Pro
515 520 525
His Ala Lys Arg Gln Asp Val Thr Val Leu Gly Ser Gln Glu Gly Ala
530 535 540
Met His Ser Ala Leu Ala Gly Ala Thr Glu Val Asp Ser Gly Asp Gly
545 550 555 560
Asn His Met Phe Ala Gly His Leu Lys Cys Lys Val Arg Met Glu Lys
565 570 575
Leu Arg Ile Lys Gly Met Ser Tyr Thr Met Cys Ser Gly Lys Phe Ser
580 585 590
Ile Asp Lys Glu Met Ala Glu Thr Gln His Gly Thr Thr Val Val Lys
595 600 605
Val Lys Tyr Glu Gly Ala Gly Ala Pro Cys Lys Val Pro Ile Glu Ile
610 615 620
Arg Asp Val Asn Lys Glu Lys Val Val Gly Arg Ile Ile Ser Ser Thr
625 630 635 640
Pro Leu Ala Glu Asn Thr Asn Ser Ala Thr Asn Ile Glu Leu Glu Pro
645 650 655
Pro Phe Gly Asp Ser Tyr Ile Val Ile Gly Val Gly Asn Ser Ala Leu
660 665 670
Thr Leu His Trp Phe Arg Lys Gly Ser Ser Ile Gly Lys Met Phe Glu
675 680 685
Ser Thr Tyr Arg Gly Ala Lys Arg Met Ala Ile Leu Gly Glu Thr Ala
690 695 700
Trp Asp Phe Gly Ser Val Gly Gly Leu Phe Thr Ser Leu Gly Lys Ala
705 710 715 720
Val His Gln Val Phe Gly Ser Val Tyr Thr Thr Met Phe Gly Gly Val
725 730 735
Ser Trp Met Ile Arg Ile Leu Ile Gly Phe Leu Val Leu Trp Ile Gly
740 745 750
Thr Asn Ser Arg Asn Thr Ser Met Ala Met Thr Cys Ile Ala Val Gly
755 760 765
Gly Ile Thr Leu Phe Leu Gly Phe Thr Val Gln Ala Asp Ser Gly Cys
770 775 780
Ala Ile Asp Ile Ser Arg Gln Glu Leu Arg Cys Gly Ser Gly Val Phe
785 790 795 800
Ile His Asn Asp Val Glu Ala Trp Met Asp Arg Tyr Lys Tyr Tyr Pro
805 810 815
Glu Thr Pro Gln Gly Leu Ala Lys Ile Ile Gln Lys Ala His Lys Glu
820 825 830
Gly Val Cys Gly Leu Arg Ser Val Ser Arg Leu Glu His Gln Met Trp
835 840 845
Glu Ala Val Lys Asp Glu Leu Asn Thr Leu Leu Lys Glu Asn Gly Val
850 855 860
Asp Leu Ser Val Val Val Glu Lys Gln Glu Gly Met Tyr Lys Ser Ala
865 870 875 880
Pro Lys Arg Leu Thr Ala Thr Thr Glu Lys Leu Glu Ile Gly Trp Lys
885 890 895
Ala Trp Gly Lys Ser Ile Leu Phe Ala Pro Glu Leu Ala Asn Asn Thr
900 905 910
Phe Val Val Asp Gly Pro Glu Thr Lys Glu Cys Pro Thr Gln Asn Arg
915 920 925
Ala Trp Asn Ser Leu Glu Val Glu Asp Phe Gly Phe Gly Leu Thr Ser
930 935 940
Thr Arg Met Phe Leu Lys Val Arg Glu Ser Asn Thr Thr Glu Cys Asp
945 950 955 960
Ser Lys Ile Ile Gly Thr Ala Val Lys Asn Asn Leu Ala Ile His Ser
965 970 975
Asp Leu Ser Tyr Trp Ile Glu Ser Arg Leu Asn Asp Thr Trp Lys Leu
980 985 990
Glu Arg Ala Val Leu Gly Glu Val Lys Ser Cys Thr Trp Pro Glu Thr
995 1000 1005
His Thr Leu Trp Gly Asp Gly Ile Leu Glu Ser Asp Leu Ile Ile
1010 1015 1020
Pro Val Thr Leu Ala Gly Pro Arg Ser Asn His Asn Arg Arg Pro
1025 1030 1035
Gly Tyr Lys Thr Gln Asn Gln Gly Pro Trp Asp Glu Gly Arg Val
1040 1045 1050
Glu Ile Asp Phe Asp Tyr Cys Pro Gly Thr Thr Val Thr Leu Ser
1055 1060 1065
Glu Ser Cys Gly His Arg Gly Pro Ala Thr Arg Thr Thr Thr Glu
1070 1075 1080
Ser Gly Lys Leu Ile Thr Asp Trp Cys Cys Arg Ser Cys Thr Leu
1085 1090 1095
Pro Pro Leu Arg Tyr Gln Thr Asp Ser Gly Cys Trp Tyr Gly Met
1100 1105 1110
Glu Ile Arg Pro Gln Arg His Asp Glu Lys Thr Leu Val Gln Ser
1115 1120 1125
Gln Val Asn Ala Tyr Asn Ala Asp Met Ile Asp Pro Phe Gln Leu
1130 1135 1140
Gly Leu Leu Val Val Phe Leu Ala Thr Gln Glu Val Leu Arg Lys
1145 1150 1155
Arg Trp Thr Ala Lys Ile Ser Met Pro Ala Ile Leu Ile Ala Leu
1160 1165 1170
Leu Val Leu Val Phe Gly Gly Ile Thr Tyr Thr Asp Val Leu Arg
1175 1180 1185
Tyr Val Ile Leu Val Gly Ala Ala Phe Ala Glu Ser Asn Ser Gly
1190 1195 1200
Gly Asp Val Val His Leu Ala Leu Met Ala Thr Phe Lys Ile Gln
1205 1210 1215
Pro Val Phe Met Val Ala Ser Phe Leu Lys Ala Arg Trp Thr Asn
1220 1225 1230
Gln Glu Asn Ile Leu Leu Met Leu Ala Ala Val Phe Phe Gln Met
1235 1240 1245
Ala Tyr Tyr Asp Ala Arg Gln Ile Leu Leu Trp Glu Ile Pro Asp
1250 1255 1260
Val Leu Asn Ser Leu Ala Val Ala Trp Met Ile Leu Arg Ala Ile
1265 1270 1275
Thr Phe Thr Thr Thr Ser Asn Val Val Val Pro Leu Leu Ala Leu
1280 1285 1290
Leu Thr Pro Gly Leu Arg Cys Leu Asn Leu Asp Val Tyr Arg Ile
1295 1300 1305
Leu Leu Leu Met Val Gly Ile Gly Ser Leu Ile Arg Glu Lys Arg
1310 1315 1320
Ser Ala Ala Ala Lys Lys Lys Gly Ala Ser Leu Leu Cys Leu Ala
1325 1330 1335
Leu Ala Ser Thr Gly Leu Phe Asn Pro Met Ile Leu Ala Ala Gly
1340 1345 1350
Leu Ile Ala Cys Asp Pro Asn Arg Lys Arg Gly Trp Pro Ala Thr
1355 1360 1365
Glu Val Met Thr Ala Val Gly Leu Met Phe Ala Ile Val Gly Gly
1370 1375 1380
Leu Ala Glu Leu Asp Ile Asp Ser Met Ala Ile Pro Met Thr Ile
1385 1390 1395
Ala Gly Leu Met Phe Ala Ala Phe Val Ile Ser Gly Lys Ser Thr
1400 1405 1410
Asp Met Trp Ile Glu Arg Thr Ala Asp Ile Ser Trp Glu Ser Asp
1415 1420 1425
Ala Glu Ile Thr Gly Ser Ser Glu Arg Val Asp Val Arg Leu Asp
1430 1435 1440
Asp Asp Gly Asn Phe Gln Leu Met Asn Asp Pro Gly Ala Pro Trp
1445 1450 1455
Lys Ile Trp Met Leu Arg Met Val Cys Leu Ala Ile Ser Ala Tyr
1460 1465 1470
Thr Pro Trp Ala Ile Leu Pro Ser Val Val Gly Phe Trp Ile Thr
1475 1480 1485
Leu Gln Tyr Thr Lys Arg Gly Gly Val Leu Trp Asp Thr Pro Ser
1490 1495 1500
Pro Lys Glu Tyr Lys Lys Gly Asp Thr Thr Thr Gly Val Tyr Arg
1505 1510 1515
Ile Met Thr Arg Gly Leu Leu Gly Ser Tyr Gln Ala Gly Ala Gly
1520 1525 1530
Val Met Val Glu Gly Val Phe His Thr Leu Trp His Thr Thr Lys
1535 1540 1545
Gly Ala Ala Leu Met Ser Gly Glu Gly Arg Leu Asp Pro Tyr Trp
1550 1555 1560
Gly Ser Val Lys Glu Asp Arg Leu Cys Tyr Gly Gly Pro Trp Lys
1565 1570 1575
Leu Gln His Lys Trp Asn Gly Gln Asp Glu Val Gln Met Ile Val
1580 1585 1590
Val Glu Pro Gly Arg Asn Val Lys Asn Val Gln Thr Lys Pro Gly
1595 1600 1605
Val Phe Lys Thr Pro Glu Gly Glu Ile Gly Ala Val Thr Leu Asp
1610 1615 1620
Phe Pro Thr Gly Thr Ser Gly Ser Pro Ile Val Asp Lys Asn Gly
1625 1630 1635
Asp Val Ile Gly Leu Tyr Gly Asn Gly Val Ile Met Pro Asn Gly
1640 1645 1650
Ser Tyr Ile Ser Ala Ile Val Gln Gly Glu Arg Met Asp Glu Pro
1655 1660 1665
Ile Pro Ala Gly Phe Glu Pro Glu Met Leu Arg Lys Lys Gln Ile
1670 1675 1680
Thr Val Leu Asp Leu His Pro Gly Ala Gly Lys Thr Arg Arg Ile
1685 1690 1695
Leu Pro Gln Ile Ile Lys Glu Ala Ile Asn Arg Arg Leu Arg Thr
1700 1705 1710
Ala Val Leu Ala Pro Thr Arg Val Val Ala Ala Glu Met Ala Glu
1715 1720 1725
Ala Leu Arg Gly Leu Pro Ile Arg Tyr Gln Thr Ser Ala Val Pro
1730 1735 1740
Arg Glu His Asn Gly Asn Glu Ile Val Asp Val Met Cys His Ala
1745 1750 1755
Thr Leu Thr His Arg Leu Met Ser Pro His Arg Val Pro Asn Tyr
1760 1765 1770
Asn Leu Phe Val Met Asp Glu Ala His Phe Thr Asp Pro Ala Ser
1775 1780 1785
Ile Ala Ala Arg Gly Tyr Ile Ser Thr Lys Val Glu Leu Gly Glu
1790 1795 1800
Ala Ala Ala Ile Phe Met Thr Ala Thr Pro Pro Gly Thr Ser Asp
1805 1810 1815
Pro Phe Pro Glu Ser Asn Ser Pro Ile Ser Asp Leu Gln Thr Glu
1820 1825 1830
Ile Pro Asp Arg Ala Trp Asn Ser Gly Tyr Glu Trp Ile Thr Glu
1835 1840 1845
Tyr Thr Gly Lys Thr Val Trp Phe Val Pro Ser Val Lys Met Gly
1850 1855 1860
Asn Glu Ile Ala Leu Cys Leu Gln Arg Ala Gly Lys Lys Val Val
1865 1870 1875
Gln Leu Asn Arg Lys Ser Tyr Glu Thr Glu Tyr Pro Lys Cys Lys
1880 1885 1890
Asn Asp Asp Trp Asp Phe Val Ile Thr Thr Asp Ile Ser Glu Met
1895 1900 1905
Gly Ala Asn Phe Lys Ala Ser Arg Val Ile Asp Ser Arg Lys Ser
1910 1915 1920
Val Lys Pro Thr Ile Ile Thr Glu Gly Glu Gly Arg Val Ile Leu
1925 1930 1935
Gly Glu Pro Ser Ala Val Thr Ala Ala Ser Ala Ala Gln Arg Arg
1940 1945 1950
Gly Arg Ile Gly Arg Asn Pro Ser Gln Val Gly Asp Glu Tyr Cys
1955 1960 1965
Tyr Gly Gly His Thr Asn Glu Asp Asp Ser Asn Phe Ala His Trp
1970 1975 1980
Thr Glu Ala Arg Ile Met Leu Asp Asn Ile Asn Met Pro Asn Gly
1985 1990 1995
Leu Ile Ala Gln Phe Tyr Gln Pro Glu Arg Glu Lys Val Tyr Thr
2000 2005 2010
Met Asp Gly Glu Tyr Arg Leu Arg Gly Glu Glu Arg Lys Asn Phe
2015 2020 2025
Leu Glu Leu Leu Arg Thr Ala Asp Leu Pro Val Trp Leu Ala Tyr
2030 2035 2040
Lys Val Ala Ala Ala Gly Val Ser Tyr His Asp Arg Arg Trp Cys
2045 2050 2055
Phe Asp Gly Pro Arg Thr Asn Thr Ile Leu Glu Asp Asn Asn Glu
2060 2065 2070
Val Glu Val Ile Thr Lys Leu Gly Glu Arg Lys Ile Leu Arg Pro
2075 2080 2085
Arg Trp Ile Asp Ala Arg Val Tyr Ser Asp His Gln Ala Leu Lys
2090 2095 2100
Ala Phe Lys Asp Phe Ala Ser Gly Lys Arg Ser Gln Ile Gly Leu
2105 2110 2115
Ile Glu Val Leu Gly Lys Met Pro Glu His Phe Met Gly Lys Thr
2120 2125 2130
Trp Glu Ala Leu Asp Thr Met Tyr Val Val Ala Thr Ala Glu Lys
2135 2140 2145
Gly Gly Arg Ala His Arg Met Ala Leu Glu Glu Leu Pro Asp Ala
2150 2155 2160
Leu Gln Thr Ile Ala Leu Ile Ala Leu Leu Ser Val Met Thr Met
2165 2170 2175
Gly Val Phe Phe Leu Leu Met Gln Arg Lys Gly Ile Gly Lys Ile
2180 2185 2190
Gly Leu Gly Gly Ala Val Leu Gly Val Ala Thr Phe Phe Cys Trp
2195 2200 2205
Met Ala Glu Val Pro Gly Thr Lys Ile Ala Gly Met Leu Leu Leu
2210 2215 2220
Ser Leu Leu Leu Met Ile Val Leu Ile Pro Glu Pro Glu Lys Gln
2225 2230 2235
Arg Ser Gln Thr Asp Asn Gln Leu Ala Val Phe Leu Ile Cys Val
2240 2245 2250
Met Thr Leu Val Ser Ala Val Ala Ala Asn Glu Met Gly Trp Leu
2255 2260 2265
Asp Lys Thr Lys Ser Asp Ile Ser Ser Leu Phe Gly Gln Arg Ile
2270 2275 2280
Glu Val Lys Glu Asn Phe Ser Met Gly Glu Phe Leu Leu Asp Leu
2285 2290 2295
Arg Pro Ala Thr Ala Trp Ser Leu Tyr Ala Val Thr Thr Ala Val
2300 2305 2310
Leu Thr Pro Leu Leu Lys His Leu Ile Thr Ser Asp Tyr Ile Asn
2315 2320 2325
Thr Ser Leu Thr Ser Ile Asn Val Gln Ala Ser Ala Leu Phe Thr
2330 2335 2340
Leu Ala Arg Gly Phe Pro Phe Val Asp Val Gly Val Ser Ala Leu
2345 2350 2355
Leu Leu Ala Ala Gly Cys Trp Gly Gln Val Thr Leu Thr Val Thr
2360 2365 2370
Val Thr Ala Ala Thr Leu Leu Phe Cys His Tyr Ala Tyr Met Val
2375 2380 2385
Pro Gly Trp Gln Ala Glu Ala Met Arg Ser Ala Gln Arg Arg Thr
2390 2395 2400
Ala Ala Gly Ile Met Lys Asn Ala Val Val Asp Gly Ile Val Ala
2405 2410 2415
Thr Asp Val Pro Glu Leu Glu Arg Thr Thr Pro Ile Met Gln Lys
2420 2425 2430
Lys Val Gly Gln Ile Met Leu Ile Leu Val Ser Leu Ala Ala Val
2435 2440 2445
Val Val Asn Pro Ser Val Lys Thr Val Arg Glu Ala Gly Ile Leu
2450 2455 2460
Ile Thr Ala Ala Ala Val Thr Leu Trp Glu Asn Gly Ala Ser Ser
2465 2470 2475
Val Trp Asn Ala Thr Thr Ala Ile Gly Leu Cys His Ile Met Arg
2480 2485 2490
Gly Gly Trp Leu Ser Cys Leu Ser Ile Thr Trp Thr Leu Ile Lys
2495 2500 2505
Asn Met Glu Lys Pro Gly Leu Lys Arg Gly Gly Ala Lys Gly Arg
2510 2515 2520
Thr Leu Gly Glu Val Trp Lys Glu Arg Leu Asn Gln Met Thr Lys
2525 2530 2535
Glu Glu Phe Thr Arg Tyr Arg Lys Glu Ala Ile Ile Glu Val Asp
2540 2545 2550
Arg Ser Ala Ala Lys His Ala Arg Lys Glu Gly Asn Val Thr Gly
2555 2560 2565
Gly His Pro Val Ser Arg Gly Thr Ala Lys Leu Arg Trp Leu Val
2570 2575 2580
Glu Arg Arg Phe Leu Glu Pro Val Gly Lys Val Ile Asp Leu Gly
2585 2590 2595
Cys Gly Arg Gly Gly Trp Cys Tyr Tyr Met Ala Thr Gln Lys Arg
2600 2605 2610
Val Gln Glu Val Arg Gly Tyr Thr Lys Gly Gly Pro Gly His Glu
2615 2620 2625
Glu Pro Gln Leu Val Gln Ser Tyr Gly Trp Asn Ile Val Thr Met
2630 2635 2640
Lys Ser Gly Val Asp Val Phe Tyr Arg Pro Ser Glu Cys Cys Asp
2645 2650 2655
Thr Leu Leu Cys Asp Ile Gly Glu Ser Ser Ser Ser Ala Glu Val
2660 2665 2670
Glu Glu His Arg Thr Ile Arg Val Leu Glu Met Val Glu Asp Trp
2675 2680 2685
Leu His Arg Gly Pro Arg Glu Phe Cys Val Lys Val Leu Cys Pro
2690 2695 2700
Tyr Met Pro Lys Val Ile Glu Lys Met Glu Leu Leu Gln Arg Arg
2705 2710 2715
Tyr Gly Gly Gly Leu Val Arg Asn Pro Leu Ser Arg Asn Ser Thr
2720 2725 2730
His Glu Met Tyr Trp Val Ser Arg Ala Ser Gly Asn Val Val His
2735 2740 2745
Ser Val Asn Met Thr Ser Gln Val Leu Leu Gly Arg Met Glu Lys
2750 2755 2760
Arg Thr Trp Lys Gly Pro Gln Tyr Glu Glu Asp Val Asn Leu Gly
2765 2770 2775
Ser Gly Thr Arg Ala Val Gly Lys Pro Leu Leu Asn Ser Asp Thr
2780 2785 2790
Ser Lys Ile Lys Asn Arg Ile Glu Arg Leu Arg Arg Glu Tyr Ser
2795 2800 2805
Ser Thr Trp His His Asp Glu Asn His Pro Tyr Arg Thr Trp Asn
2810 2815 2820
Tyr His Gly Ser Tyr Asp Val Lys Pro Thr Gly Ser Ala Ser Ser
2825 2830 2835
Leu Val Asn Gly Val Val Arg Leu Leu Ser Lys Pro Trp Asp Thr
2840 2845 2850
Ile Thr Asn Val Thr Thr Met Ala Met Thr Asp Thr Thr Pro Phe
2855 2860 2865
Gly Gln Gln Arg Val Phe Lys Glu Lys Val Asp Thr Lys Ala Pro
2870 2875 2880
Glu Pro Pro Glu Gly Val Lys Tyr Val Leu Asn Glu Thr Thr Asn
2885 2890 2895
Trp Leu Trp Ala Phe Leu Ala Arg Glu Lys Arg Pro Arg Met Cys
2900 2905 2910
Ser Arg Glu Glu Phe Ile Arg Lys Val Asn Ser Asn Ala Ala Leu
2915 2920 2925
Gly Ala Met Phe Glu Glu Gln Asn Gln Trp Arg Ser Ala Arg Glu
2930 2935 2940
Ala Val Glu Asp Pro Lys Phe Trp Glu Met Val Asp Glu Glu Arg
2945 2950 2955
Glu Ala His Leu Arg Gly Glu Cys His Thr Cys Ile Tyr Asn Met
2960 2965 2970
Met Gly Lys Arg Glu Lys Lys Pro Gly Glu Phe Gly Lys Ala Lys
2975 2980 2985
Gly Ser Arg Ala Ile Trp Phe Met Trp Leu Gly Ala Arg Phe Leu
2990 2995 3000
Glu Phe Glu Ala Leu Gly Phe Leu Asn Glu Asp His Trp Leu Gly
3005 3010 3015
Arg Lys Asn Ser Gly Gly Gly Val Glu Gly Leu Gly Leu Gln Lys
3020 3025 3030
Leu Gly Tyr Ile Leu Arg Glu Val Gly Thr Arg Pro Gly Gly Lys
3035 3040 3045
Ile Tyr Ala Asp Asp Thr Ala Gly Trp Asp Thr Arg Ile Thr Arg
3050 3055 3060
Ala Asp Leu Glu Asn Glu Ala Lys Val Leu Glu Leu Leu Asp Gly
3065 3070 3075
Glu His Arg Arg Leu Ala Arg Ala Ile Ile Glu Leu Thr Tyr Arg
3080 3085 3090
His Lys Val Val Lys Val Met Arg Pro Ala Ala Asp Gly Arg Thr
3095 3100 3105
Val Met Asp Val Ile Ser Arg Glu Asp Gln Arg Gly Ser Gly Gln
3110 3115 3120
Val Val Thr Tyr Ala Leu Asn Thr Phe Thr Asn Leu Ala Val Gln
3125 3130 3135
Leu Val Arg Met Met Glu Gly Glu Gly Val Ile Gly Pro Asp Asp
3140 3145 3150
Val Glu Lys Leu Thr Lys Gly Lys Gly Pro Lys Val Arg Thr Trp
3155 3160 3165
Leu Phe Glu Asn Gly Glu Glu Arg Leu Ser Arg Met Ala Val Ser
3170 3175 3180
Gly Asp Asp Cys Val Val Lys Pro Leu Asp Asp Arg Phe Ala Thr
3185 3190 3195
Ser Leu His Phe Leu Asn Ala Met Ser Lys Val Arg Lys Asp Ile
3200 3205 3210
Gln Glu Trp Lys Pro Ser Thr Gly Trp Tyr Asp Trp Gln Gln Val
3215 3220 3225
Pro Phe Cys Ser Asn His Phe Thr Glu Leu Ile Met Lys Asp Gly
3230 3235 3240
Arg Thr Leu Val Val Pro Cys Arg Gly Gln Asp Glu Leu Val Gly
3245 3250 3255
Arg Ala Arg Ile Ser Pro Gly Ala Gly Trp Asn Val Arg Asp Thr
3260 3265 3270
Ala Cys Leu Ala Lys Ser Tyr Ala Gln Met Trp Leu Leu Leu Tyr
3275 3280 3285
Phe His Arg Arg Asp Leu Arg Leu Met Ala Asn Ala Ile Cys Ser
3290 3295 3300
Ala Val Pro Val Asn Trp Val Pro Thr Gly Arg Thr Thr Trp Ser
3305 3310 3315
Ile His Ala Gly Gly Glu Trp Met Thr Thr Glu Asp Met Leu Glu
3320 3325 3330
Val Trp Asn Arg Val Trp Ile Glu Glu Asn Glu Trp Met Glu Asp
3335 3340 3345
Lys Thr Pro Val Glu Lys Trp Ser Asp Val Pro Tyr Ser Gly Lys
3350 3355 3360
Arg Glu Asp Ile Trp Cys Gly Ser Leu Ile Gly Thr Arg Ala Arg
3365 3370 3375
Ala Thr Trp Ala Glu Asn Ile Gln Val Ala Ile Asn Gln Val Arg
3380 3385 3390
Ala Ile Ile Gly Asp Glu Lys Tyr Val Asp Tyr Met Ser Ser Leu
3395 3400 3405
Lys Arg Tyr Glu Asp Thr Thr Leu Val Glu Asp Thr Val Leu
3410 3415 3420
<210> 21
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 具有II型接合的 WN/DEN1嵌合体的 C蛋白信号序列
<400> 21
Gly Gly Lys Thr Gly Ile Thr Met Leu Leu Met Leu Leu Pro Thr Ala
1 5 10 15
Leu Ala
<210> 22
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 具有II型接合的 WN/DEN2嵌合体的 C蛋白信号序列
<400> 22
Gly Gly Lys Thr Gly Ile Gly Met Ile Ile Met Leu Ile Pro Thr Val
1 5 10 15
Met Ala
<210> 23
<211> 18
<212> PRT
<213> 人工序列
<220>
<223> 具有II型接合的 WN/DEN4嵌合体的 C蛋白信号序列
<400> 23
Gly Gly Lys Thr Gly Ile Ile Thr Leu Leu Cys Leu Ile Pro Thr Val
1 5 10 15
Met Ala
Claims (33)
1.一种核酸嵌合体，其包含：第一核酸分子，其包含来自西尼罗病毒基因组的5'非编码区、编码非结构蛋白和C蛋白的核酸以及3'非编码区，其中所述C蛋白包含18个氨基酸长的信号序列，所述信号序列包含来自所述西尼罗病毒基因组的prM信号序列的头六个氨基酸和来自登革病毒基因组的prM信号序列的最后十二个氨基酸；和第二核酸分子，其与所述第一核酸分子可操作地连接，编码来自登革病毒基因组的prM蛋白和E蛋白，其中所述第二核酸在所述来自登革热病毒基因组的prM信号序列的部分的3'，并在所述来自西尼罗病毒基因组的非结构蛋白和3'非编码区的5'，其中所述嵌合体从5’到3’方向包含（1）所述西尼罗病毒5'非编码区，（2）所述编码西尼罗病毒C蛋白的核酸，所述C蛋白包括来自西尼罗病毒prM信号序列的头六个氨基酸和来自登革病毒prM信号序列的最后十二个氨基酸的prM信号序列，（3）所述编码登革病毒prM蛋白的核酸，（4）所述编码登革病毒E蛋白的核酸，（5）编码7个西尼罗病毒非结构蛋白的核酸，和（6）所述西尼罗病毒3'非编码区。
2. 权利要求1的核酸嵌合体，其中所述西尼罗病毒prM信号序列的头六个氨基酸包含GGKTGI（SEQ ID NO: 2的氨基酸106-111）。
3. 权利要求1或权利要求2的核酸嵌合体，其中所述登革病毒prM信号序列的最后十二个氨基酸包含SEQ ID NO: 4、6或8中任一个的氨基酸103-114，或SEQ ID NO: 10的氨基酸102-113。
4.权利要求1的核酸嵌合体，其中所述E蛋白在对应于DEN1、DEN2或DEN4的E蛋白第347位氨基酸位置或DEN3的E蛋白第345位氨基酸位置的氨基酸处的氨基酸被亮氨酸置换。
5. 权利要求1所述的核酸嵌合体，其包含SEQ ID NO: 15的核酸序列。
6. 权利要求1的核酸嵌合体，其中所述核酸嵌合体编码SEQ ID NO: 16的氨基酸序列。
7.一种核酸嵌合体，其包含：第一核酸分子，其包含来自西尼罗病毒基因组的5'非编码区、编码非结构蛋白和C蛋白的核酸以及3'非编码区；和第二核酸分子，其与所述第一核酸分子可操作地连接，编码来自登革病毒基因组的prM蛋白和E蛋白，其中所述第二核酸在所述来自西尼罗病毒基因组的C蛋白的3'，并在所述来自西尼罗病毒基因组的非结构蛋白和3'非编码区的5'，以及其中所述E蛋白在对应于DEN1、DEN2或DEN4的E蛋白第347位氨基酸位置或DEN3的E蛋白第345位氨基酸位置的氨基酸处的氨基酸被亮氨酸置换，其中所述嵌合体从5’到3’方向包含（1）所述西尼罗病毒5'非编码区，（2）所述编码西尼罗病毒C蛋白的核酸，所述C蛋白包括来自西尼罗病毒prM信号序列的18个氨基酸，（3）所述编码登革病毒prM蛋白的核酸，（4）所述编码登革病毒E蛋白的核酸，（5）编码7个西尼罗病毒非结构蛋白的核酸，和（6）所述西尼罗病毒3'非编码区。
8. 权利要求7的核酸嵌合体，其包含SEQ ID NO: 17的核酸序列。
9. 权利要求7的核酸嵌合体，其中所述核酸嵌合体编码包含SEQ ID NO: 18的氨基酸序列。
10.一种核酸嵌合体，其包含：第一核酸分子，其包含来自西尼罗病毒基因组的5'非编码区、编码非结构蛋白和C蛋白的核酸以及3'非编码区，其中所述C蛋白包含来自登革病毒基因组的prM信号序列；和第二核酸分子，其与所述第一核酸分子可操作地连接，编码来自所述登革病毒基因组的prM蛋白和E蛋白，其中所述第二核酸在所述来自登革热病毒基因组的prM信号序列的3'，并在所述来自西尼罗病毒基因组的非结构蛋白和3'非编码区的5'；其中：所述C蛋白包含以下的一个或多个置换：对应于DEN1、DEN2或DEN3的第101位氨基酸位置的氨基酸的丝氨酸置换；对应于DEN1、DEN2或DEN3的第102位氨基酸位置或DEN4的第101位氨基酸位置的氨基酸的脯氨酸置换；所述prM蛋白包含以下的一个或多个置换：对应于DEN1、DEN2、DEN3或DEN4的第22位氨基酸位置的氨基酸的脯氨酸置换，对应于DEN1、DEN2、DEN3或DEN4的第154位氨基酸位置的氨基酸的苏氨酸置换，或对应于DEN1、DEN2、DEN3或DEN4的第155位氨基酸位置的氨基酸的亮氨酸置换；和/或所述E蛋白包含以下的一个或多个置换：对应于DEN1、DEN2、DEN3或DEN4的第171位氨基酸位置的氨基酸的异亮氨酸置换；对应于DEN1、DEN2或DEN4的第311位氨基酸位置或DEN3的第309位氨基酸位置的氨基酸的丙氨酸置换；对应于DEN1、DEN2或DEN4的第347位氨基酸位置或DEN3的第345位氨基酸位置的氨基酸的亮氨酸置换；对应于DEN1、DEN2或DEN4的第397位氨基酸位置或DEN3的第395位氨基酸位置的氨基酸的丙氨酸置换；对应于DEN1、DEN2或DEN4的第417位氨基酸位置或DEN3的第415位氨基酸位置的氨基酸的丙氨酸置换，其中所述嵌合体从5’到3’方向包含（1）所述西尼罗病毒5'非编码区，（2）所述编码西尼罗病毒C蛋白的核酸，所述C蛋白包括来自登革病毒基因组的prM信号序列的14个氨基酸，（3）所述编码登革病毒prM蛋白的核酸，（4）所述编码登革病毒E蛋白的核酸，（5）编码7个西尼罗病毒非结构蛋白的核酸，和（6）所述西尼罗病毒3'非编码区。
11. 权利要求10的核酸嵌合体，其包含SEQ ID NO: 19的核酸序列。
12. 权利要求10的核酸嵌合体，其中所述核酸嵌合体编码包含SEQ ID NO: 20的氨基酸序列。
13.一种免疫原性组合物，其包含一种或多种灭活病毒和可药用的载体，所述灭活病毒包含权利要求1至12中任一项的核酸嵌合体。
14.权利要求13的免疫原性组合物，其还包含包括WN/DEN2核酸嵌合体的灭活病毒，所述核酸嵌合体包含：第一核酸分子，其包含来自西尼罗病毒基因组的5'非编码区、编码非结构蛋白和C蛋白的核酸以及3'非编码区，其中所述C蛋白包含来自登革-2病毒基因组的prM信号序列；和第二核酸分子，其与所述第一核酸分子可操作地连接，编码来自所述登革-2病毒基因组的prM蛋白和E蛋白，其中所述第二核酸在所述来自登革病毒基因组的prM信号序列的3'并在所述来自西尼罗病毒基因组的非结构蛋白和3'非编码区的5'，以及其中所述E蛋白在对应于第203位氨基酸位置的氨基酸处的氨基酸被天冬氨酸置换，其中所述嵌合体从5’到3’方向包含（1）所述5'非编码区，（2）所述编码C蛋白的核酸，（3）所述编码prM信号序列的核酸，（4）所述编码prM蛋白的核酸，（5）所述编码E蛋白的核酸，（6）所述编码非结构蛋白的核酸，和（7）所述3'非编码区。
15. 权利要求14的免疫原性组合物，其中所述WN/DEN2嵌合体包含SEQ ID NO: 13的核酸序列。
16. 权利要求14的免疫原性组合物，其中所述WN/DEN2嵌合体编码包含SEQ ID NO: 14的氨基酸序列。
17.权利要求13的免疫原性组合物，其还包含包括WN/DEN1核酸嵌合体的灭活病毒，所述核酸嵌合体包含：第一核酸分子，其包含来自西尼罗病毒基因组的5'非编码区、编码非结构蛋白和C蛋白的核酸以及3'非编码区，其中所述C蛋白包含来自登革-1病毒基因组的prM信号序列；和第二核酸分子，其与所述第一核酸分子可操作地连接，编码来自所述登革-1病毒基因组的prM蛋白和E蛋白，其中所述第二核酸在所述来自登革病毒基因组的prM信号序列的3'并在所述来自西尼罗病毒基因组的非结构蛋白和3'非编码区的5'，其中所述嵌合体从5’到3’方向包含（1）所述5'非编码区，（2）所述编码C蛋白的核酸，（3）所述编码prM信号序列的核酸，（4）所述编码prM蛋白的核酸，（5）所述编码E蛋白的核酸，（6）所述编码非结构蛋白的核酸，和（7）所述3'非编码区。
18. 权利要求17的免疫原性组合物，其中所述WN/DEN1嵌合体包含SEQ ID NO: 11的核酸序列。
19. 权利要求17的免疫原性组合物，其中所述WN/DEN1嵌合体编码包含SEQ ID NO: 12的氨基酸序列。
20.权利要求13的免疫原性组合物，其中所述组合物包含包括WN/DEN1核酸嵌合体的病毒、包括WN/DEN2核酸嵌合体的病毒、包括WN/DEN3核酸嵌合体的病毒以及包括WN/DEN4核酸嵌合体的病毒。
21. 一种免疫原性组合物，其包含一种或多种灭活的WN/DENV嵌合病毒和可药用的载体，所述灭活的WN/DENV嵌合病毒包含SEQ ID NO: 11、13、17或19的核酸序列。
22.权利要求13或21的免疫原性组合物，其还包含一种或多种佐剂。
23.权利要求13或21的免疫原性组合物，其中所述一种或多种灭活病毒是经纯化的。
24.权利要求13或21的免疫原性组合物，其中所述一种或多种灭活病毒是通过化学处理和物理处理中的一种或多种被灭活的。
25.权利要求24的免疫原性组合物，其中所述物理处理是照射。
26.权利要求13或21的免疫原性组合物，其用于在受试者中引起针对一种或多种登革病毒的免疫应答。
27.权利要求13至25中任一项的免疫原性组合物在制备用于在受试者中引起针对一种或多种登革病毒的免疫应答的疫苗中的用途。
28.权利要求27的用途，其中所述免疫应答包含针对DEN1、DEN2、DEN3以及DEN4中的每一种的免疫应答。
29.权利要求27或权利要求28的用途，其中所述疫苗包括一到五个剂量的免疫原性组合物。
30.权利要求27或权利要求28的用途，其中所述疫苗还包括一种或多种佐剂。
31.一种方法，其包括灭活包含一种或多种权利要求1至12中任一项的核酸嵌合体的病毒。
32.权利要求31的方法，其中灭活所述病毒包括用化学灭活剂、高压、紫外线照射、γ照射或其组合处理所述病毒。
33.权利要求31或32的方法，其还包括纯化所述灭活病毒。
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| WO2009134717A1 (en) * | 2008-04-30 | 2009-11-05 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services, Centers For Disease Control And Prevention | Chimeric west nile/dengue viruses |
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| EP3158061A1 (en) | 2017-04-26 |
| US20170114330A1 (en) | 2017-04-27 |
| BR112016029201B1 (pt) | 2023-11-14 |
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| BR112016029201B8 (pt) | 2023-12-05 |
| AU2015276929A1 (en) | 2016-12-22 |
| WO2015196094A1 (en) | 2015-12-23 |
| BR112016029201A2 (pt) | 2017-10-17 |
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