CN111278981A - 用于表达g蛋白偶联受体或其亚基的构建体及其用途 - Google Patents

用于表达g蛋白偶联受体或其亚基的构建体及其用途 Download PDF

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CN111278981A
CN111278981A CN201880069162.7A CN201880069162A CN111278981A CN 111278981 A CN111278981 A CN 111278981A CN 201880069162 A CN201880069162 A CN 201880069162A CN 111278981 A CN111278981 A CN 111278981A
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下村一平
山本岳
上泷将史
飞田直哉
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Abstract

本发明的目的在于提供用于表达G蛋白偶联受体的构建体及其利用。本发明的构建体是用于表达G蛋白偶联受体蛋白或其亚基的构建体，其特征在于在单一载体中从5’侧起依次包含：编码G蛋白α亚基蛋白的核酸、包含IRES序列的核酸、以及编码G蛋白偶联受体蛋白或其亚基的核酸。

Description

用于表达G蛋白偶联受体或其亚基的构建体及其用途
技术领域
本发明涉及用于表达G蛋白偶联受体或其亚基的构建体、导入了本发明的构建体的转化细胞、使用了本发明的转化细胞的物质的生理反应的测定方法、用于测定物质的生理反应的本发明的转化细胞的用途、包含本发明的转化细胞且用于物质的生理反应的测定方法的试剂盒。
背景技术
1.G蛋白偶联受体及G蛋白介导的信号转导
G蛋白偶联受体是在真核生物的细胞质膜上或细胞内部的组成膜上存在的受体的形式的1种。感受来自细胞外(膜外)的各种信号(神经递质、激素、化学物质、光等)时，G蛋白偶联受体发生结构变化，激活与膜内侧结合的三聚体G蛋白，进行信号转导。
G蛋白是结合于细胞膜的内表面、且Gβγ二聚体牢固地结合于Gα亚基的异源三聚体。配体结合于G蛋白偶联受体而被激活时，结合于G蛋白偶联受体的G蛋白使其具有的GDP从Gα亚基分离，与新的GTP分子结合(GDP型→GTP型的转换)。通过该转换，Gα亚基、Gβγ二聚体及G蛋白偶联受体分别分离。分离后的Gα亚基激活其下游的效应器蛋白。
G蛋白偶联受体及其下游的G蛋白控制了嗅觉、味觉、视觉、神经传递、代谢、细胞分化及细胞增殖、炎症反应及免疫应答等细胞内信号网络中的大量基本生理化学反应。
2.关于味觉及嗅觉的知识
味觉是在物质进入口中时，特别是通过存在于舌表面的特异性受体与物质结合而产生的感觉。哺乳动物类的味觉由5种基本味、即咸味、酸味、甜味、鲜味、苦味构成，可以认为是由这些基本味综合而形成。目前认为，咸味、酸味是通过在舌表面的味蕾中存在的味细胞附近侧的细胞膜上表达的若干离子通道型受体而感知的。
对于甜味、鲜味、苦味，可以认为是通过由味细胞中存在的G蛋白偶联受体和与其偶联的G蛋白介导的信号转导而感知的。具体而言，已知苦味可以通过命名为T2R家族的分子(苦味受体)(人类为25种)感受，甜味可以通过T1R2+T1R3的异源二聚体(甜味受体)感受，鲜味可以通过T1R1+T1R3的异源二聚体(鲜味受体)感受。
对于味觉信息的传递机制的机理，通常理解如下。即，首先，味觉物质与味细胞的受体结合时，经过细胞内的第二信使(IP3、DAG)等介导的信息传递过程使细胞内的钙浓度上升。接着，供给至细胞内的钙离子使神经递质释放至突触，在神经细胞中产生动作电位，其结果是，以受体为起点的味觉信号从味觉神经传递至脑，识别、判断味觉信息，这是通常的说法。
嗅觉受体也与苦味受体、甜味受体、鲜味受体等味觉受体同样是G蛋白偶联受体。嗅觉受体存在于嗅上皮的嗅细胞上。嗅细胞是人体中神经细胞与外界直接接触的唯一部位，其另一端与脑中被称为嗅球的区域直接连接。“气味物质”是分子量30～300左右的低分子化合物，据说地球上存在数十万种气味物质。人类有400种以上的嗅觉受体已被鉴定。气味物质结合于嗅觉受体时，与苦味受体、甜味受体、鲜味受体等味觉受体同样地经过细胞内的第二信使等介导的信息传递过程而使细胞内的钙浓度上升。
3.G蛋白偶联受体激动剂的评价
食品、饮料等中包含的化学物质、神经递质、激素等与G蛋白偶联受体结合而使其发生结构变化，有可能成为激活结合于膜内侧的G蛋白的一系列信号转导的G蛋白偶联受体激动剂。希望简便且效率良好地进行这些G蛋白偶联受体激动剂的候选物质的生理反应评价。只要能够适当地进行蛋白质偶联受体激动剂的候选物质的生理反应评价，就可以实现饮料食品、医药品等的味道、品质等的改善、蛋白质偶联受体激动剂的用量的调节等有益的效果。
另一方面，对于上述食品、饮料等中包含的物质，也可以进行基于感官试验的评价。然而，已知基于感官试验的评价伴随以下的实质性问题：不容易保证评价的客观性，评价所花费的人工、时间、费用的负担很大，无法在短时间对大量物质进行评价等。
因此，作为替代感官试验的评价方法，报告了如下方法：制备表达G蛋白偶联受体及Gα蛋白的细胞系，向这样的细胞系直接添加G蛋白偶联受体激动剂(候选化合物)来对效果进行评价。
在用于G蛋白偶联受体激动剂的评价的细胞系中，需要在同一细胞中表达G蛋白偶联受体蛋白和Gα蛋白。为了使这2种蛋白表达，通常广泛使用了将包含编码各蛋白质的核酸的2种载体同时或依次进行基因导入的共基因导入法。这些例如为以下的方式。
(a)用包含编码Gα蛋白的核酸的载体、和包含编码G蛋白偶联受体蛋白或其亚基的核酸的载体对宿主细胞进行共转染；
(b)用包含编码G蛋白偶联受体蛋白或其亚基的核酸的载体对稳定表达Gα蛋白的细胞株进行转化。
作为使用了共基因导入法的例子，例如，对于苦味受体，记载于Chem.Senses 35,p.157-170,2010；The Journal of Neuroscience,23(19),p.7376-7380,2003；BiochemBiophys Res Commun,365(4):p.851-855,2008。另外，对于甜味受体，记载于日本特开2008-13570号公报、日本特开2008-228690号公报、WO2007-121604号公报。
然而，在任何情况下均无法获得制备难度高(成功率低)、稳定的数据。因此，不能认为是具有足以用于进行G蛋白偶联受体激动剂的评价的品质的细胞系。
作为表达2种蛋白质的方法，除了共基因导入法以外，还已知使用将表达2种蛋白质的各核酸插入1个载体而成的共表达载体的方法。通常，即使将表达2种蛋白质的2种核酸串联地直接插入单一的载体，越是位于远离启动子的位置的核酸，越难以被翻译，蛋白质的表达量越低。因此，越是位于远离启动子的位置的核酸，越需要想办法提高翻译效率。
日本专利5905187记载了“一种甜味受体表达构建体，其是将编码味觉受体的味觉受体亚基T1R2及T1R3、以及G蛋白α亚基的各基因插入同一质粒而成的，所述甜味受体表达构建体在位于EF-1α启动子的下游、且在紧邻编码甜味受体亚基T1R2的基因之后，通过IRES序列连接编码G蛋白α亚基的基因，进一步在位于其下游存在CMV启动子的下游、且在紧邻编码甜味受体亚基T1R3的基因之后，通过IRES序列连接编码G蛋白α亚基的基因”。日本专利5905187的构建体从5’侧起依次具有EF-1α启动子-T1R2-IRES-Gα-CMV启动子-TIR3-IRES-Gα这样的特定结构。在该构建体中，T1R2及T1R3配置于各特定的启动子的下游、以及IRES的上游。
IRES是能够进行非帽依赖性翻译的翻译起始来进一步提高蛋白质合成的效率的RNA因子。已知，通常与受到帽依赖性翻译的上游蛋白相比，IRES介导的翻译具有低效率的倾向。
在本发明之前，尚未得到具有足以用于进行G蛋白偶联受体激动剂的评价的品质的细胞系。
现有技术文献
专利文献
专利文献1：日本特开2008-13570号公报
专利文献2：日本特开2008-228690号公报
专利文献3：WO2007-121604号公报
非专利文献
非专利文献1：Chem.Senses 35,p.157-170,2010
非专利文献2：The Journal of Neuroscience,23(19),p.7376-7380,2003
非专利文献3：Biochem Biophys Res Commun,365(4):p.851-855,2008
非专利文献4：Molecular BioSystems,7,p.911-919,2011
非专利文献5：Proc.Natl.Acad.Sci.USA,Vol.88,p.5587-5591,1991
非专利文献6：Journal of Virology,Vol.86,No.3,p.1468-1486,2012
非专利文献7：GENES&DEVELOPMENT,Vol,15,p.1593-1612,20
非专利文献8：Archives of Physiology and Biochemistry Vol.110p.137-45,2002
非专利文献9：Nature Genetics,Vol.32,p.397-401,2002；Cell,Vol.100,p.703-711,2000
发明内容
发明要解决的课题
本发明人等为了解决上述问题而进行了深入研究，结果发现，在用于表达G蛋白偶联受体蛋白或其亚基的构建体中，通过在单一载体中从5’侧起依次配置编码G蛋白α亚基蛋白的核酸、包含IRES序列的核酸、以及编码G蛋白偶联受体蛋白或其亚基的核酸，可以高效率表达G蛋白偶联受体蛋白或其亚基，能够对G蛋白偶联受体激动剂以高效率应答，从而想到了本发明。
可以认为，由配置于IRES的3’侧的基因编码的蛋白质的表达量低。因此，在本发明中，其特征在于以高效率表达G蛋白偶联受体蛋白或其亚基，这是与现有知识相反的。
解决课题的方法
本发明包含以下的方式，但并不限定于此。
[方式1]
一种构建体，其用于表达G蛋白偶联受体蛋白或其亚基，所述构建体在单一载体中从5’侧起依次包含：编码G蛋白α亚基蛋白的核酸、包含IRES序列的核酸、以及编码G蛋白偶联受体蛋白或其亚基的核酸。
[方式2]
根据方式1所述的构建体，其中，G蛋白偶联受体或其亚基是视紫红质样受体类型或代谢性谷氨酸受体/代谢性信息素受体类型的G蛋白偶联受体。
[方式3]
根据方式1所述的构建体，其中，G蛋白偶联受体是视紫红质样受体类型的G蛋白偶联受体。
[方式4]
根据方式1所述的构建体，其中，G蛋白偶联受体为苦味受体。
[方式5]
根据方式1～4中任一项所述的构建体，其中，载体为质粒载体。
[方式6]
根据方式1～4中任一项所述的构建体，其中，载体为包含CMV启动子的质粒载体。
[方式7]
根据方式1～4中任一项所述的构建体，其中，载体为包含CMV启动子及潮霉素抗性基因的质粒载体。
[方式8]
根据方式1～4中任一项所述的构建体，其中，载体为包含EF1α启动子的质粒载体。
[方式9]
根据方式1～4中任一项所述的构建体，其中，载体为包含EF1α启动子及嘌呤霉素抗性基因的质粒载体。
[方式10]
根据方式1～9中任一项所述的构建体，其中，IRES序列为2型的IRES序列。
[方式11]
根据方式1～10中任一项所述的构建体，其中，IRES序列为来自脑心肌炎病毒的IRES序列。
[方式12]
根据方式1～7中任一项所述的构建体，其中，在编码G蛋白偶联受体蛋白或其亚基的核酸的5’侧包含编码具有提高G蛋白偶联受体蛋白或其亚基向细胞膜的转移的功能的多肽的核酸。
[方式13]
根据方式12所述的构建体，其中，提高G蛋白偶联受体蛋白或其亚基向细胞膜的转移的多肽是包含大鼠的生长抑素受体的N末端45个氨基酸的多肽、或包含牛的视紫红质的N末端39个氨基酸的多肽。
[方式14]
根据方式1～13中任一项所述的构建体，其中，G蛋白α亚基蛋白为Gq家族的G蛋白α亚基蛋白、Gi家族的G蛋白α亚基蛋白、Gs家族的G蛋白α亚基蛋白、或者它们的嵌合蛋白。
[方式15]
根据方式1～14中任一项所述的构建体，其中，G蛋白α亚基蛋白为Gα16、Gαgust或Gαolf、或者它们的嵌合蛋白。
[方式16]
根据方式1～15中任一项所述的构建体，其中，G蛋白α亚基蛋白为人Gα16/大鼠Gαgust。
[方式17]
根据方式16所述的构建体，其中，G蛋白α亚基蛋白为人Gα16/大鼠Gαgust43。
[方式18]
根据方式1～17中任一项所述的构建体，其中，G蛋白偶联受体蛋白为人的G蛋白偶联受体蛋白。
[方式19]
基因导入了方式1～18中任一项所述的构建体的转化细胞。
[方式20]
物质的生理反应的测定方法，该方法包括：将物质添加于方式19所述的转化细胞，对该物质引起的生理反应进行测定。
[方式21]
根据方式20所述的测定方法，其中，物质为苦味物质、气味物质、鲜味物质或甜味物质、或者对这些物质的调节物质。
[方式22]
方式19所述的转化细胞在测定物质的生理反应中的用途。
[方式23]
一种用于物质的生理反应的测定方法的试剂盒，其包含方式19所述的转化细胞，所述测定方法通过将物质添加于该转化细胞、并对该物质引起的生理反应进行测定来进行。
发明的效果
用本发明的构建体进行转化而成的细胞以高效率表达G蛋白偶联受体蛋白或其亚基，以高效率对G蛋白偶联受体激动剂进行应答。本发明的转化细胞提供具有足以用于进行G蛋白偶联受体激动剂的评价的品质的细胞系。
附图说明
图1示出了实施例1中制备的构建体的结构。图1中，“CMV”是指CMV启动子。
图2是测定T2R16稳定表达株对苦味物质水杨苷的应答而得到的结果。
图3是测定T2R40稳定表达株对苦味物质地芬尼多(difenidol)的应答而得到的结果、以及测定T2R43稳定表达株对苦味物质奎宁的应答而得到的结果。
图4是测定T2R16短暂表达细胞对苦味物质水杨苷的应答而得到的结果。
图5是测定T2R16短暂表达细胞对T2R非依赖性Gα16激动剂(异丙肾上腺素)的应答而得到的结果。
图6是测定T2R16短暂表达细胞中的T2R16的表达量而得到的结果。
图7是对T2R16稳定表达株在冷冻保存前后的应答强度进行比较的结果。
图8是将Gα-T2R40稳定表达株对T2R40激动剂的应答强度与对Gα激动剂的应答强度进行比较来调查相关性而得到的结果。
图9是将Gα-T1R2及T1R3共基因导入，测定使其短暂表达的细胞株(Gα-T1R2+T1R3)中的T1R2的表达量而得到的结果。
图10是将Gα-T1R2及T1R3共基因导入，测定使其短暂表达的细胞株(Gα-T1R2+T1R3)对T2R非依赖性Gα16激动剂(异丙肾上腺素)的应答而得到的结果。
图11是将Gα-T1R2及T1R3共基因导入，测定使其短暂表达的细胞株(Gα-T1R2+T1R3)对甜味物质阿斯巴甜的应答而得到的。
图12是将Gα-T1R3及T1R2共基因导入，测定使其短暂表达的细胞株(Gα-T1R3+T1R2)中的T1R3的表达量而得到的结果。
图13是将Gα-T1R3及T1R2共基因导入，测定使其短暂表达的细胞株(Gα-T1R3+T1R2)对T2R非依赖性Gα16激动剂(异丙肾上腺素)的应答而得到的结果。
图14是将Gα-T1R3及T1R2共基因导入，测定使其短暂表达的细胞株(Gα-T1R3+T1R2)对甜味物质甜蜜素(cyclamate)的应答而得到的结果。
图15是使绿色荧光蛋白(EmGFP)在IRES的上游及下游表达时测定EmGFP的表达量而得到的结果。
图16是对使pEAK10-T2R16-Gα及pEAK10-Gα-T2R16短暂表达的HEK293T细胞中的T2R16表达量进行调查的结果。
图17涉及7种T2R亚型(苦味受体)，是调查短暂表达细胞对各激动剂(苦味物质)的应答而得到的结果。
图18涉及T2R38亚型(苦味受体)，是调查稳定表达细胞对激动剂(6-正丙基硫尿嘧啶)的应答而得到的结果。黑色是T2R38的结果，斜线是对照(未导入表达载体Gα-T2R38的细胞株(HEK293T))的结果。
图19是对14种T2R亚型(苦味受体)在短暂表达细胞中的表达量进行调查的结果(与T2R4相比)。
图20是对嗅觉受体(OR3A1)在短暂表达细胞中的应答进行调查的结果。斜线表示导入OR3A1-Gαolf的结果，黑色表示导入Gαolf-OR3A1的结果。虚线(OR3A1+Gαolf)表示将OR3A1、Gαolf各基因分别导入pcDNA、并共基因导入至HEK293T的结果。
图21示出了嗅觉受体(OR3A1)的短暂表达细胞中的OR3A1、Gαolf的表达量。斜线表示OR3A1的结果，黑色表示Gαolf的结果。“OR3A1+Gαolf”是将OR3A1、Gαolf各基因分别导入pcDNA、并共基因导入至HEK293T时的结果。
具体实施方式
本发明涉及用于表达G蛋白偶联受体或其亚基的构建体、基因导入本发明的构建体而成的转化细胞、使用了本发明的转化细胞的物质的生理反应的测定方法、用于测定物质的生理反应的本发明转化细胞的用途、包含本发明的转化细胞且用于物质的生理反应的测定方法的试剂盒。以下，对本具体实施方式非限定性地进行说明。
I.用于表达G蛋白偶联受体或其亚基的构建体
在一个方式中，本发明涉及用于表达G蛋白偶联受体或其亚基的构建体。本发明的构建体的特征在于，在单一载体中从5’侧起依次包含：编码G蛋白α亚基蛋白的核酸、包含IRES序列的核酸、以及编码G蛋白偶联受体蛋白或其亚基的核酸。
(1)G蛋白偶联受体或其亚基
“G蛋白偶联(型)受体”(G protein-coupled receptor:GPCR)是真核生物的细胞质膜上或细胞内部的组成膜上存在的受体的形式的1种。由于具有7个螺旋结构贯穿细胞膜(或细胞内的组成膜)、且N末端位于膜外、C末端位于膜内的特征性结构，因此也称为“7次跨膜受体”。膜外环包含两个高度保守的半胱氨酸残基，通过二硫键使受体结构稳定化。感受来自细胞外(膜外)的各种信号(神经递质、激素、化学物质、光等)时，G蛋白偶联受体发生结构变化，使结合于膜内侧的三聚体G蛋白激活而进行信号转导。G蛋白偶联受体控制了嗅觉、味觉、视觉、神经传递、代谢、细胞分化及细胞增殖、炎症反应及免疫应答等细胞内信号网络中的大量基本的生理化学反应。
基于氨基酸序列、药理动力学、功能等的相似性，将G蛋白偶联受体分类为6个类型(Molecular BioSystems,7,p.911-919,2011)。
类型A：视紫红质样受体
类型B：促胰液素受体家族
类型C：代谢性谷氨酸受体/代谢性信息素受体
类型D：真菌交配因子受体
类型E：环状AMP(cAMP)受体
类型F：卷曲(Frizzled)、平滑(Smoothened)
(i)类型A：视紫红质样受体
类型A的视紫红质样受体的N末端的细胞外区域较短，通过多个跨膜区域形成配体结合部位。类型A的视紫红质样受体占G蛋白偶联受体的80％以上，包括苦味受体、嗅觉受体、视紫红质、肾上腺素受体、毒蕈碱型乙酰胆碱受体等。作为视紫红质样受体中保守的氨基酸序列，有位于第3个跨膜区域的膜内侧的E/DRY(Asp/Glu、Arg、Tyr)模体。
苦味受体是属于视紫红质样受体的G蛋白偶联受体。在人及小鼠的第6号染色体中被鉴定为T2R家族。在小鼠中至少35种T2R作为苦味受体发挥功能，在人中至少25种T2R作为苦味受体发挥功能。人的T2R与其配体的关系的例子如下所述。
T2R4：苯甲地那铵；
T2R10：士的宁；
T2R14：与大量结构特征不同的苦味物质非特异性结合
T2R16：β-吡喃葡萄糖苷(水杨苷(salicin))
T2R31：马兜铃酸
T2R38：具有异硫氰酸酯基的苦味物质，例如，苯基硫脲(PTC)、丙基硫尿嘧啶(PROP)
T2R40：地芬尼多
T2R43：奎宁
T2R46：苦艾素(absinthin)、士的宁、苦精(denatonium)
小鼠及人的T2R蛋白的氨基酸序列及基因的核酸序列是公知的。例如，人的25种T2R苦味受体的氨基酸序列及基因序列以下述表1中记载的登录号登记在NCBI(NationalCenter for Biotechnology Information)或GenBank。
Figure BDA0002463519700000111
Figure BDA0002463519700000121
需要说明的是，在本说明书中，只要没有特别说明，“基因”与核酸以相同含义使用，包括不包含启动子等调控序列的方式。核酸包括DNA(包含基因组DNA、cDNA这两者)、RNA(mRNA)、DNA与RNA的嵌合体。某个特定的蛋白质的“基因序列”是指编码该蛋白质的氨基酸序列的(不包括内含子)DNA序列。
嗅觉受体也与苦味受体同样地是属于视紫红质样受体的G蛋白偶联受体。嗅觉受体平均由310个氨基酸残基的长度组成，共同具有若干模体序列。特别的特征是从第3个跨膜位点至第4个膜内环存在的被称为MAYDRYVAIC的模体序列。该模体序列中，DRY(Asp/Glu、Arg、Tyr)的3个氨基酸残基也与其它视紫红质样受体是共通的，可以认为对G蛋白的激活是很重要的。大量嗅觉受体的蛋白质的氨基酸及基因的核酸序列是公知的。
例如，人的嗅觉受体的氨基酸序列及基因序列以下述表2中记载的登录号登记在NCBI或GenBank。
Figure BDA0002463519700000141
(ii)类型C：代谢性谷氨酸受体/代谢性信息素受体
除代谢性谷氨酸受体、代谢性信息素受体以外，类型C还包括甜味受体、鲜味受体、GABA(B型)受体、钙敏感受体等。在本说明书及权利要求书中称为“代谢性谷氨酸受体/代谢性信息素受体的类型”的情况下，只要没有特别说明，就是指全部的类型C。类型C的受体以同源或异源的二聚体的形式发挥功能，具有G蛋白偶联受体当中最大的500～600残基左右的细胞外区域。细胞外区域的配体结合结构域采取被称为捕蝇夹(Venus Flytrap)模块(VFTM)结构的结构。
甜味受体是属于类型C的受体，以T1R2/T1R3的异源二聚体的形式发挥功能。已有报告在作为人工甜味料的阿斯巴甜(aspartame)和纽甜(neotame)的感受中，人T1R2的N末端结构域是很重要的；在人工甜味剂甜蜜素(cyclamate)、甜味抑制物质Lactisole的感受中，人T1R3的跨膜结构域是很重要的；在甜味修饰物质Neoculin的感受中，人T1R3的N末端结构域是很重要的。甜味蛋白布那珍(Brazzein)的人T1R3的富含C结构域对敏感性是很重要的。
鲜味受体是属于类型C的受体，以T1R1/T1R3的异源二聚体的形式发挥功能。已知鲜味物质的谷氨酸及肌苷酸(IMP)与T1R1的N末端结构域结合。
构成甜味受体、鲜味受体的人T1R1、T1R2、T1R3的氨基酸序列及基因序列以下述表3中记载的登录号登记在NCBI。
Figure BDA0002463519700000161
使用本发明的构建体表达的可以是整个G蛋白偶联受体蛋白，或者也可以是其亚基。例如，包括仅表达构成作为二聚体的甜味受体或鲜味受体的亚基、T1R2、T1R3、T1R1中的任一种亚基的构建体。在该情况下，可以用其它构建体的构成二聚体的其它亚基进行共转染。或者，以在单一的载体中包含编码构成G蛋白偶联受体蛋白的多个亚基的核酸的方式构建构建体。在本发明中，以至少编码1个亚基的核酸配置在IRES的3’侧的方式构成构建体。
(iii)类型B：促胰液素受体家族
类型B的促胰液素受体家族的N末端侧细胞外区域长，形成配体结合位点。可以分为促胰液素样受体(狭义)和粘附(Adhesion)型G蛋白偶联受体这2个亚组。促胰液素样受体(狭义)包括与促胰液素、胰高血糖素、胰高血糖素样肽(GLP)、降钙素、甲状旁腺素等肽激素结合的受体。粘附(Adhesion)型G蛋白偶联受体在巨大的N末端部位具有各种结构域结构，显示出细胞外基质等的相互作用。
(iv)类型F：卷曲(Frizzled)、平滑(Smoothened)
类型F的G蛋白偶联受体包括通过Wnt信号转导通路发挥功能的10种卷曲(Frizzled)蛋白、和通过Hedgehog信号转导通路发挥功能的平滑(Smoothened)蛋白。类型F的受体在细胞外具有被称为富含半胱氨酸结构域(CRD)的由约120个氨基酸残基组成的区域，形成Wnt等配体的结合区域。
在本发明中，G蛋白偶联受体或其亚基的种类没有特别限定。至少在属于类型A的苦味受体T2R的多个种类、以及属于不同的类型C的亚基T1R2(构成甜味受体)及T1R3(构成甜味受体及鲜味受体)中确认了本发明的效果。
非限定性地，在本发明的一个方式中，优选G蛋白偶联受体或其亚基为视紫红质样受体类型(类型A)或代谢性谷氨酸受体/代谢性信息素受体类型(类型C)的G蛋白偶联受体。在本发明的一个方式中，G蛋白偶联受体是视紫红质样受体类型的G蛋白偶联受体。更优选G蛋白偶联受体为苦味受体。
G蛋白偶联受体蛋白的来源物种没有特别限定。优选为来自于动物，更优选来自于哺乳动物。哺乳动物包括例如：人、大鼠、猴、犬、猪、绵羊、马、小鼠等。在本发明的一个方式中，G蛋白偶联受体蛋白为人的G蛋白偶联受体蛋白。
(2)G蛋白α亚基
“G蛋白(鸟苷酸结合蛋白)”是属于GTP酶的组的蛋白质，并且通常是指由α、β、γ这3个亚基构成的膜受体相关异源三聚体。
G蛋白结合于细胞膜的内表面，Gβγ二聚体与Gα亚基牢固地结合在一起。配体结合于G蛋白偶联受体而激活时，将结合于G蛋白偶联受体的G蛋白所具有的GDP从Gα亚基上分离，与新的GTP分子结合(GDP型→GTP型的转换)。通过该转换，Gα亚基、Gβγ二聚体及G蛋白偶联受体各自分离。分离后的Gα亚基将其下游的效应器蛋白激活。
G蛋白α亚基由GTP酶结构域和α螺旋结构域这2个结构域形成。目前已知至少20种Gα亚基，主要分类为4个家族。
[表4]
Figure BDA0002463519700000181
在本发明中，G蛋白α亚基的种类没有特别限定。在本发明的一个方式中，G蛋白α亚基蛋白非限定性地为Gq家族的G蛋白α亚基蛋白、Gi家族的G蛋白α亚基蛋白、Gs家族的G蛋白α亚基蛋白、或者它们的嵌合蛋白。在本发明的一个方式中，G蛋白α亚基蛋白为Gα16、Gαgust或Gαolf、或者它们的嵌合蛋白。
G蛋白亚基的来源物种没有特别限定。优选来自于动物，更优选来自于哺乳动物。哺乳动物包括例如：人、大鼠、猴、犬、猪、绵羊、马、小鼠等。在本发明的一个方式中，G蛋白为人的G蛋白偶联受体蛋白。
人的Gα16例如记载于Proc.Natl.Acad.Sci.USA,Vol.88,p.5587-5591,1991，mRNA的序列以登录号M63904.1登记在GenBank。另外，人的Gα16的碱基序列及氨基酸序列记载为本申请的序列表的序列号65及66。编码人Gα16的基因例如可以从HL60细胞等培养细胞获得。
大鼠Gastducin的mRNA的序列以登录号NM_173139.1登记在NCBI。另外，大鼠Gastducin的碱基序列及氨基酸序列记载为本申请的序列表的序列号67及68。
人的Gαolf的mRNA序列以登录号AF493893.1登记在GenBank。另外，人的Gαolf的碱基序列及氨基酸序列记载为本申请的序列表的序列号69及70。
G蛋白α亚基蛋白可以是嵌合蛋白。嵌合蛋白可以是来自相同物种的不同种G蛋白α亚基的融合蛋白，也可以是来自不同物种的同种G蛋白α亚基的融合蛋白，或者还可以是来自不同物种的不同种G蛋白α亚基的融合蛋白。G蛋白α亚基蛋白n的嵌合蛋白的对G蛋白偶联受体的结合特异性、结合强度、或稳定性等特征有时与原始的G蛋白α亚基蛋白不同。通过利用包含编码这样的嵌合蛋白的核酸的构建体，可以得到具有希望特征的转化细胞。因此，具有希望特征的转化细胞可以适当用于物质的生理反应的测定方法。
在本发明的一个方式中，G蛋白α亚基蛋白为人Gα16/大鼠Gαgust。人Gα16/大鼠Gαgust是将人Gα16的C末端侧取代为大鼠Gαgust的C末端序列而成的嵌合蛋白。已经报告将Gα16的C末端侧取代为37个氨基酸残基以上的Gαgust的C末端序列而成的嵌合蛋白对苦味受体T2R应答(The Journal of Neuroscience,23(19),p.7376-7380,2003)。
取代人Gα16的大鼠Gαgust的C末端序列优选至少为25个氨基酸残基以上、30个氨基酸残基以上、35个氨基酸残基以上、37个氨基酸残基以上、40个氨基酸残基以上、43个氨基酸残基以上。取代人Gα16的大鼠Gαgust的C末端序列优选为60个氨基酸残基以下、50个氨基酸残基以下、45个氨基酸残基以下、43个氨基酸残基以下。在本发明的一个方式中，G蛋白α亚基蛋白为人Gα16/大鼠Gαgust43。
在本说明书的实施例中，将人的Gα16的序列号65的3’末端132碱基(包含终止密码子，相当于编码C末端的43个氨基酸的序列)取代为相当于大鼠味蛋白(Gastducin)的序列、即序列号67的3’末端的132碱基(包含终止密码子，相当于编码C末端的43个氨基酸的序列)(Gα16/Gαgust43(Gα))。
(3)IRES
本发明的构建体在单一载体中编码G蛋白α亚基蛋白的核酸的下游(3’侧)、且编码G蛋白偶联受体蛋白或其亚基的核酸的上游(5’侧)的位置包含含有IRES序列的核酸。IRES是Internal ribosome entry site(内部核糖体进入位点)的简称，是能够进行非帽依赖性翻译的翻译起始从而进一步提高蛋白质合成的效率的RNA因子。大量的IRES存在于RNA病毒的5’UTR(5’非翻译区域)，但没有表明在哺乳动物细胞的细胞性mRNA中存在IRES。
目前表达的病毒性IRES大致分为5个类型(Journal of Virology,Vol.86,No.3,p.1468-1486,2012)。
第1类是双顺反子病毒的IRES组。第2类是丙型肝炎病毒(HCV)及瘟病毒属的病毒的IRES，还包含结构类似的多种病毒的IRES。
另外，已知被称为1型～3型的3个类型的IRES。它们均在小RNA病毒科的5’UTR中被鉴定出来。
其中，2型主要是在口蹄疫病毒属(Aphthovirus)、心病毒属(Cardiovirus)、双埃柯病毒属(Parechovirus)中发现的IRES。另外，马鼻病毒属(Erbovirus)、Cosavirus病毒属中也存在分支成员。心病毒属(Cardiovirus)包括脑心肌炎病毒(Encephalomyocarditisvirus)(EMCV)、泰勒病毒(Theilovirus)。2型的IRES为约450碱基的长度，具有3’-末端Yn-Xm-AUG(Yn为嘧啶区，n为8～10的整数，m为18～20。)的模体，有时AUG三联体为起始密码子。2型的IRES包含H、I、J、K及L这5个主要结构域。2型的IRES在真核生物的翻译起始因子IF4E及涉及核糖体扫描的因子、例如eIF1及eIF1A等不参与的情况下发挥功能。其中，2型的IRES中的一部分需要1个或多个IRES反式激活因子(ITAFs)。ITAF为嘧啶区结合蛋白(PTB)等细胞性RNA结合蛋白。
1型的IRES是仅在肠道病毒属(Enterovirus)中发现的IRES。1型的IRES包含II-VI这5个主要结构域。2型的IRES为约450碱基的长度，与2型同样地具有3’-末端Yn-Xm-AUG的模体。其中，在1型的IRES中，该模体通过非保守的间隔区与起始密码子隔开。3型是仅在甲型肝炎病毒中发现的IRES。
对于细胞性IRES，例如记载于GENES&DEVELOPMENT,Vol,15,p.1593-1612,2001。
在本发明中，IRES的种类没有特别限定。非限定性地，在本发明的一个方式中，IRES为病毒性的IRES。在本发明的一个方式中，IRES序列为2型的IRES序列，例如，来自脑心肌炎病毒的IRES序列。来自脑心肌炎病毒的IRES的核酸序列以登录号M81861.1登记在GenBank。本说明书的实施例中使用的IRES序列为序列号71，且模仿pIRES2-EGFP载体(Clontech)的IRES部位对GenBank的登录号M81861.1的序列进行了部分修正。具体而言，在序列号71中，在碱基号1追加G，在碱基号512追加A。
(4)具有提高G蛋白偶联受体蛋白或其亚基向细胞膜的转移的功能的多肽
在一个方式中，本发明的构建体在编码G蛋白偶联受体蛋白或其亚基的核酸的5’侧包含编码具有提高G蛋白偶联受体蛋白或其亚基向细胞膜的转移的功能的多肽的核酸。
在使用了这样的构建体的情况下，在G蛋白偶联受体蛋白或其亚基的N’末端侧表达结合有这样的多肽的融合蛋白。因此，在由该构建体转化的细胞中，G蛋白偶联受体蛋白或其亚基向细胞膜的转移提高。更多G蛋白偶联受体向细胞膜转移了的转化细胞更容易用于物质的生理反应的测定方法。
在本发明中，具有提高G蛋白偶联受体蛋白或其亚基向细胞膜的转移的功能的多肽的种类只要具有“提高G蛋白偶联受体蛋白或其亚基向细胞膜转移”的功能即可，没有特别限定。“提高G蛋白偶联受体蛋白或其亚基向细胞膜转移”是指，在该多肽结合于G蛋白偶联受体蛋白或其亚基的N末端侧的情况下，与未结合的情况相比，表达的G蛋白偶联受体蛋白或其亚基从转化细胞的核向细胞膜转移的比例(显著)升高。
提高G蛋白偶联受体蛋白或其亚基向细胞膜的转移的多肽非限定性地包括：包含大鼠的生长抑素受体的全部或一部分的多肽、包含牛的视紫红质的全部或一部分的多肽(Archives of Phisiology and Biochemistry Vol.110 p.137-45,2002；NatureGenetics,Vol.32,p.397-401,2002；Cell,Vol.100,p.703-711,2000)。在本发明的一个方式中，提高G蛋白偶联受体蛋白或其亚基向细胞膜的转移的多肽是包含大鼠的生长抑素受体的N末端45个氨基酸的多肽、包含牛的视紫红质的N末端39个氨基酸的多肽、或者包含人的视紫红质的N末端21个氨基酸的多肽。
大鼠的生长抑素受体的mRNA序列以登录号NM_133522.1登记在NCBI。另外，大鼠生长抑素受体的碱基序列及氨基酸序列记载为本申请的序列表的序列号72及73。在本申请说明书的实施例中，将序列号72的5’末端的135碱基结合于编码G蛋白偶联受体的碱基序列的5’侧。
人的视紫红质的mRNA的序列以登录号NM_000539.1登记在NCBI。另外，人视紫红质的碱基序列及氨基酸序列记载为本申请的序列表的序列号74及75。
(5)载体
本发明的构建体在单一载体中是5’侧起依次包含：编码G蛋白α亚基蛋白的核酸、包含IRES序列的核酸、以及编码G蛋白偶联受体蛋白或其亚基的核酸。通过在单一载体中按照上述顺序包含上述核酸，可以获得在转化细胞中G蛋白偶联受体蛋白或其亚基的表达量升高、和/或G蛋白偶联受体蛋白或其亚基对配体物质的应答性升高的效果。在载体中，从5’侧起，按照编码G蛋白α亚基蛋白的核酸、包含IRES序列的核酸、编码G蛋白偶联受体蛋白或其亚基的核酸的顺序排列是很重要的。以往的定论是被IRES的3’侧的核酸编码的蛋白质的表达量不高。在G蛋白偶联受体蛋白或其亚基的情况下，与配置在IRES的5’侧相比，通过配置在3’侧，表达量提高，本发明人等基于这样的见解而想到了本发明。
需要说明的是，在G蛋白偶联受体为例如甜味受体(T1R2/T1R3)、鲜味受体(T1R1/T1R3)这样的二聚体的情况下，可以仅将编码构成二聚体的一个亚基的核酸如上所述与编码G蛋白α亚基蛋白的核酸、IRES一起包含于单一载体。也可以使编码其它的亚基的核酸包含于其它载体，和上述载体进行共转染。
载体的种类只要是能够在希望的细胞中表达蛋白质的表达载体即可，没有特别限定。非限定性地包括质粒载体、噬菌体载体、粘粒载体、病毒载体等。本领域技术人员可以根据表达蛋白质的细胞的种类来选择适当的载体。
在本发明的一个方式中，载体为质粒载体。质粒载体包含例如pFRT/lacZeo、pUC12、pUC13、pUC19、pBR322、pBR325、pSH15、pSH19、pUB110、pC194等。Thermo FisherScientific公司的pcDNA(商标)系列(pcDNA3、pcDNA5可以用作哺乳动物细胞中的表达载体。作为哺乳动物细胞中的表达载体，除此以外，也可以使用pEAK10(Edge biosystem公司)。
本发明的载体优选包含启动子。启动子的种类没有特别限定，可以包含例如来自人巨细胞病毒的启动子(CMV启动子)、EF1α启动子等。在本发明的一个方式中，载体为包含CMV启动子的质粒载体、或包含EF1α启动子的质粒载体。
本发明的载体优选包含用于选择转化后的细胞的选择标记。选择标记的种类没有特别限定，包括药物抗性基因、荧光蛋白基因等公知的启动子。通过包含选择标记，可以选择稳定地表达蛋白质的细胞株。
作为本发明的一个方式，选择标记为药物抗性基因。药物抗性基因非限定性地包括潮霉素抗性基因、嘌呤霉素抗性基因、新霉素抗性基因、杀稻瘟菌素抗性基因等。
在本发明的一个方式中，载体为包含CMV启动子及潮霉素抗性基因的质粒载体。这样的载体的一例是本说明书的实施例中使用的pcDNA3.1 Hygro(+)载体(Thermo FisherScientific公司)。
在本发明的另一个方式中，载体为包含EF1α启动子及嘌呤霉素抗性基因的质粒载体。这样的载体的一例是pEAK10(Edge biosystem公司)。
分别以本申请的序列表的序列号80及81表示本说明书的实施例中使用的pcDNA3.1Hygro(+)载体及pEAK10载体的序列。序列号80的碱基895-942是插入目标基因的多克隆位点(MCS)。序列号81的碱基1892-2823相当于EF-1α启动子序列，碱基2844-2845相当于插入目标基因的部位，碱基3293-3892相当于嘌呤霉素抗性基因序列。
II.转化细胞
另外，本发明涉及基因导入了上述本发明的构建体的转化细胞。用于基因导入本发明的构建体来制备转化细胞的宿主细胞的种类只要是能够通过基因导入而导入外源性核酸进行转化的细胞即可，没有特别限定。
例如，细胞可以选自动物细胞、昆虫细胞、植物细胞、酵母菌及细菌。本说明书中的动物细胞的来源没有特别限定。优选为来自于属于脊椎动物门的动物的细胞。脊椎动物门包含无颔总纲(Agnatha)和有颔下门(Gnathostomata)。有颔下门包含哺乳纲、鸟纲、两栖纲、爬行纲等。通常优选为来自属于被称为哺乳动物的哺乳纲的动物的细胞。哺乳动物没有特别限定，优选包括小鼠、大鼠、人、猴、猪、犬、绵羊、山羊等。
来自哺乳动物的细胞包括“细胞系”，所述细胞系是可以长时间在体外保持，具有一定的稳定性质，能够半永久性传代培养的培养细胞。存在例如PC12细胞(来自于大鼠肾上腺髓质)、CHO细胞(来自于中国仓鼠卵巢)、HEK293细胞(来自于人胚胎肾)、HL-60细胞(来自于人白血球细胞)、HeLa细胞(来自于人子宫颈癌)、Vero细胞(来自于非洲绿猴肾上皮细胞)、MDCK细胞(来自于犬肾肾小管上皮细胞)、HepG2细胞(来自于人肝癌)等来自于包含人的各种生物的各种组织的细胞系。
本说明书中的植物细胞的来源没有特别限定。以包括苔藓植物、蕨类植物、种子植物的植物的细胞作为对象。种子植物细胞的来源植物包括任意的单子叶植物、双子叶植物。本说明书中的昆虫细胞的来源也没有特别限定。本说明书中的古细菌及细菌的种类也没有特别限定。
非限定性地，作为用于制备本发明的转化细胞的宿主细胞，可以利用HEK293细胞、CHO细胞、32D细胞、HeLa细胞、COS细胞、BHK细胞等真核细胞。在本发明的一个方式中，宿主细胞为HEK293细胞。
使用本发明的构建体对宿主细胞进行基因导入(转化)的方法没有特别限定。对于将核酸基因导入动物细胞、植物细胞、细菌的方法，已知各种适合的方法(例如，MOLECULARCLONING:A Laboratory Manual(Fourth Edition),Michael R Green and JosephSambrook,2012,(Cold Spring Harbor Laboratory Press))。本领域技术人员可以根据载体的种类、细胞的种类等适当使用适合的基因导入法。例如，在质粒载体等非病毒载体的情况下，已知有脂质体转染法、电穿孔法、显微注射法等基因导入法。
转化细胞可以是稳定地表达G蛋白偶联受体蛋白或其亚基的细胞(稳定表达株)，也可以是瞬时表达的细胞(短暂表达细胞)。“稳定表达株”是指，例如，通过选择标记确认利用基因导入而包含于构建体的核酸被稳定地导入宿主细胞的基因组，因此可稳定地表达G蛋白偶联受体蛋白或其亚基的细胞株。“短暂表达细胞”是指，未确认构建体中包含的核酸被稳定地导入宿主细胞的基因组，无法确认稳定地表达G蛋白偶联受体蛋白或其亚基的细胞。
本发明的转化细胞具有如下特征：G蛋白偶联受体蛋白或其亚基的表达量升高、和/或G蛋白偶联受体蛋白或其亚基对配体物质的应答性升高。“G蛋白偶联受体蛋白或其亚基的表达量升高”是指，与使用现有技术表达G蛋白偶联受体蛋白或其亚基的情况相比，其表达量升高。“G蛋白偶联受体蛋白或其亚基对配体物质的应答性升高”是指，与使用本发明之前的现有技术表达G蛋白偶联受体蛋白或其亚基的情况相比，其对配体物质的应答性升高。
“现有技术”例如包括以下的方式。
(1)共基因导入
(1a)用包含编码Gα蛋白的核酸的载体和包含编码G蛋白偶联受体蛋白或其亚基的核酸的载体对宿主细胞进行共转染；
(1b)用包含编码G蛋白偶联受体蛋白或其亚基的核酸的载体对稳定表达Gα蛋白的细胞株进行转化。
(2)包含IRES的共表达载体
用单一载体进行转化，所述单一载体从5’侧起依次包含启动子-编码G蛋白偶联受体蛋白或其亚基的核酸-IRES-编码Gα蛋白的核酸。
与使用现有技术表达G蛋白偶联受体蛋白或其亚基的情况相比，本发明的转化细胞的稳定性优异。稳定性包括通常的细胞培养条件下的稳定性、冷冻保存等保存条件下的稳定性。例如，在本说明书的实施例中，即使在冷冻保存下保存了1个月左右的情况下，对配体的应答强度与冷冻保存前相比也为0.8以上，基本上没有降低。相比之下，在共基因导入(Double stable)中，对配体的应答强度的冷冻干燥后降低至低于0.6。
III.物质的生理反应的测定方法。
另外，本发明涉及物质的生理反应的测定方法。本发明的测定方法包括：将物质添加于本发明的转化细胞，对该物质引起的生理反应进行测定的工序。
“物质”只要是与G蛋白偶联受体结合而能够成为激动剂的物质即可，没有特别限定。物质在G蛋白偶联受体中引起结构变化，激活结合于膜内侧的G蛋白，进行信号转导，包括：食品、饮料等中包含的化学物质、气味分子、神经递质、激素等。信号引起嗅觉、味觉、视觉、神经传递、代谢、细胞分化及细胞增殖、炎症反应及免疫应答等细胞内信号网络中的生理反应。物质根据G蛋白偶联受体的种类而不同。
在一个方式中，物质是苦味物质、气味物质、鲜味物质或甜味物质、或者对这些物质的调节物质。
“苦味物质”只要是人能够感受到苦味的物质即可，没有特别限定。包括例如苯甲地那铵、士的宁、β-吡喃葡萄糖苷(水杨苷(salicin))、马兜铃酸、具有异硫氰酸酯基的苦味物质(例如，苯基硫脲(PTC)、丙基硫尿嘧啶(PROP))、地芬尼多、奎宁、苦艾素、苦精(denatonium)。
“气味物质”是分子量30～300左右的低分子化合物。例如，作为脑内激素的血清素的基本骨架是吲哚这样的粪便气味的物质，多巴胺、肾上腺素的骨架与香草的气味的香草醛相似。只要是具有挥发性的性质的低分子有机化合物，任何物质均可作为气味物质。气味由各种食物、植物、动物产生，即使是被认为嗅觉退化的人类，也能够识别1万种左右。作为“气味物质”的例子，作为具体的“气味物质”的例子，可以列举：作为麝香(musk)气味的主成分的麝香酮、作为麝猫(civet)香的主成分的灵猫酮、产生三色堇的花的香气的α-紫罗兰酮、丁香的花的香气的主成分α-松油醇、产生留兰香的香气的(-)5R-香芹酮、以及产生鱼气味的甲胺、二甲胺、三甲胺等。
“鲜味物质”例如只要人能够感受鲜味的物质即可，没有特别限定。例如，包括谷氨酸及肌苷酸(IMP)。
“甜味物质”例如只要是人能够感受甜味的物质即可，没有特别限定。广泛包括例如：葡萄糖、果糖、半乳糖、棉子糖、木糖、蔗糖、麦芽糖、乳糖、淀粉糖浆、异构糖、异麦芽低聚糖、低聚果糖、低聚半乳糖、低聚木糖、低聚乳果糖、大豆低聚糖、海藻糖、山梨糖醇、甘露醇、麦芽糖醇、木糖醇、赤藓糖醇、乳糖醇、异麦芽酚、还原淀粉糖浆、还原帕拉金糖、和三盆糖、黑糖、三温糖、蜂蜜、糖蜜、甘草提取物及枫糖浆等糖质系甜味剂、以及阿斯巴甜(aspartame)、糖精、甘素、甜菊苷、甜叶菊提取物、甘草素、安赛蜜-K、SUCRALOSE(三氯蔗糖)(注册商标；San-Ei Gen F.F.I.公司)、甜蜜素(cyclamate)、阿力甜、纽甜、紫苏葶(perillartine)、应乐果甜蛋白(monellin)、仙茅甜蛋白(curculin)(注册商标；ADEKA)等非糖质系甜味剂。
“苦味物质、气味物质、鲜味物质或甜味物质的调节物质”是指，虽然单独时不产生苦味、气味、鲜味、甜味，但通过与苦味物质、气味物质、鲜味物质或甜味物质一起被感受而增强、修饰或抑制各物质的味觉、嗅觉的物质。
例如，“苦味物质的调节物质”包括Benecort BMI(花王)、丙磺舒(Probenecid)等。“气味物质的调节物质”包括作为嗅觉抑制剂的2.4.6-三氯茴香醚、香叶醇等。“甜味物质的调节物质”包括甜味抑制物质Lactisole、甜味抑制物质匙羹藤酸、甜味修饰物质Neoculin等。
为了使用本发明的转化细胞测定某种物质的生理反应，例如，如下所述地进行。
将给定数量的本发明的转化细胞分布在具有大量孔(24孔、48孔、96孔、384孔等)的微孔板的各孔中(例如，1万～50万个/孔)，在给定的培养基(例如，DMEM培养基)中进行培养。在细胞培养后，在添加了特定的物质的情况下，测定上述稳定培养细胞株中发生的生理反应，基于该测定结果评价物质的生理反应。测定生理反应时，可以根据物质的种类适当选择随G蛋白偶联受体的激活而变化的现象。
例如，苦味受体、甜味受体、鲜味受体等味觉受体被激活时，经过细胞内的第二信使(IP3(三磷酸肌醇)、DAG)等介导的信息传递过程，细胞内的钙浓度升高。因此，作为测定对象的生理反应，可以列举随味觉受体的激活而变化的细胞内的第二信使的变化、细胞内的钙浓度的变化等。因此，可以通过测定细胞内的第二信使或钙浓度的变化来测定生理反应。
例如，可以进行钙成像法，在所述钙成像法中，通过使用荧光钙指示剂对由苦味、甜味或鲜味等味觉刺激引起的细胞内钙浓度变化进行观察。对于荧光钙指示剂，要求在生理上能够变化的钙浓度下荧光特性发生变化，并且此时的变化是钙特异性诱导的。荧光钙指示剂的例子包括：Fluo-8(注册商标)(AAT Bioquest公司)(激发波长490nm、荧光波长514nm)、Fluo-4AM((AAT Bioquest公司)(激发波长490nm、荧光波长525nm)、Fura-2AM(Thermo Fisher公司)(激发波长340nm、荧光波长380nm)。
气味物质的生理反应的测定可以使用例如在气味物质的生理反应测定中测定由气味物质的嗅觉刺激所引起的细胞内cAMP浓度的变化的方法。作为测定细胞内cAMP的方法，可以列举：使用标记了荧光或HRP等酶的cAMP和抗cAMP抗体的荧光偏振免疫分析法或竞争性免疫分析法、或者基因导入在cAMP应答序列(CRE)的下游插入荧光素酶而成的载体、并通过荧光素酶分析法进行测定的方法等。
本发明包括本发明的转化细胞的用途，其用于测定物质的生理反应。
本发明在单一载体中包含编码G蛋白α亚基蛋白的核酸和编码G蛋白偶联受体蛋白或其亚基的核酸。因此可以推测，转化细胞中的G蛋白α亚基蛋白和G蛋白偶联受体蛋白的表达量具有正相关关系。在本发明的转化细胞中，G蛋白偶联受体对G蛋白偶联受体激动剂的应答性与对Gα激动剂的应答强度显示出很高的正相关性(实施例7，图8)。因此，在添加了物质(G蛋白偶联受体激动剂)的转化细胞中，通过测定G蛋白α亚基对Gα激动剂的应答强度，也可以推测对物质的生理应答强度。
IV.用于物质的生理反应的测定方法的试剂盒
另外，本发明还涉及用于物质的生理反应的测定方法的试剂盒，其包含本发明的转化细胞，所述测定方法通过将物质添加于该转化细胞、并对该物质引起的生理反应进行测定来进行。
本发明的试剂盒除了本发明的转化细胞以外，还可以包含用于物质的生理反应的测定方法的必要材料、使用说明书等。用于物质的生理反应的测定方法的必要材料是指，例如，用于保持/培养转化细胞的培养基、用于测定由物质的生理反应产生的第二信使或钙浓度的试剂(例如，用于测定钙浓度的荧光钙指示剂等)等。
本发明涉及用于物质的生理反应的测定方法的装置，其包含转化细胞，且所述装置将物质添加于该转化细胞、并对该物质引起的生理反应进行测定。本发明的装置包含本发明的试剂盒、用于测定由物质的生理反应产生的第二信使或钙浓度的设备等。
作为用于测定对苦味物质、气味物质、鲜味物质或甜味物质、或对这些物质的调节物质等呈味物质的生理反应的装置的例子，例如，由Intelligent Sensor TechnologyInc.开发了“人造脂质膜味觉传感器”(http://www.insent.co.jp/products/taste#sensor#index.html)。该味觉传感器将由各种呈味物质和静电相互作用、疏水性相互作用所引起的人造脂质膜的膜电位的变化作为传感器输出，利用电脑进行检测。例如，Intelligent Sensor Technology Inc.正在销售味道识别装置TS-5000Z。本发明的装置利用本发明的转化细胞来代替这样的传感器中的人工脂质膜。具体而言，将本发明的转化细胞与人工膜替换并固定于装置中，使其与物质发生作用，测定细胞内的第二信使或钙浓度的变化，由此测定物质的生理反应。本发明的装置在使用后通过清洗等去除试验物质，从而能够反复用于测定。
实施例
以下，基于实施例对本发明详细进行说明，但本发明并不限定于这些实施例。本领域技术人员可以基于本说明书的记载而容易地对本发明进行修改/变更，这些也包含于本发明的技术范围。
实施例1 构建体的构成及制备方法
在本实施例中，制备了用于表达G蛋白偶联受体蛋白的构建体。本发明的构建体在单一载体中从5’侧起依次包含：编码G蛋白α亚基蛋白的核酸、包含IRES序列的核酸、以及包含G蛋白偶联受体蛋白的核酸。
分别通过PCR对以下3种基因进行了扩增。
·在5’末端添加了从大鼠生长抑素受体3(ssr3)的起始密码子至第135个碱基的基因序列、在3’末端添加了V5表位序列的人苦味受体(T2R16)表达基因(ssr/T2R16/V5)
需要说明的是，V5表位序列是用于调查T2R的蛋白质表达量的抗体识别标签(碱基序列：序列号76)；
·来自于脑心肌炎病毒(Encephalomyocarditis virus)的IRES；以及
·将人的G蛋白α亚基G16的末端129碱基替换为大鼠的味蛋白(gustducin)(Ggust)的末端129碱基而成的Gα16/gust表达基因(Gα16/Gαgust43)(序列号77)。
使用In-Fusion HD Cloning Kit(Clontech公司)将得到的基因片段插入pcDNA3.1Hygro(+)载体(Thermo Fisher Scientific公司)的多克隆位点。插入顺序如下所述。
本发明的载体：Gα-T2R16
Gα16/Gαgust43-IRES-ssr/T2R16/V5
比较例的载体：T2R16-Gα
ssr/T2R16/V5-IRES-Gα16/Gαgust43
将各载体的构成示于图1。
实施例2 包含本发明的构建体的稳定表达株的制备
在本实施例中，制作了导入本发明的构建体(Gα-T2R16)、且稳定表达苦味受体T2R16的细胞株(T2R16稳定表达株)。
具体而言，使用Lipofectamine(注册商标)3000(Thermo Fisher Scientific公司)将实施例1中制备的Gα-T2R16及T2R16-Gα各质粒载体5μg基因导入以1×106个接种在培养容器中的人胚胎肾细胞株HEK293T(从理化学研究获得)。在48小时培养后，向培养基中添加100μg/mL的潮霉素B，进行15天左右的培养，由此进行了药物抗性筛选。将获得了药物抗性的细胞逐个接种于96孔板的各孔中，由此进行了克隆。在10天左右的培养后，得到了稳定表达株。
实施例3 稳定表达株对苦味物质的应答测定
(1)Gα-T2R16稳定表达株的应答测定
在本实施例中，测定了实施例2的T2R16稳定表达株对苦味物质的应答。
将基于实施例2中记载的方法制备的T2R16稳定表达株以2×104个/孔分别接种于96孔板。细胞的培养培养基中含有绿色荧光钙指示剂Fluo-8(注册商标)(AAT Bioquest公司)，调查了Fluo-8在细胞株中的吸收。Fluo-8(注册商标)适合细胞内的钙动力学的检测，成为GPCR活性的指标。
在490nm下使吸收了Fluo-8(注册商标)的细胞激发，测定了514nm的荧光强度。在测定中，添加作为T2R16激动剂的水杨苷(10、3、1、0.3、或0.1mM)，得到了添加后40秒钟的荧光强度的最大值。计算荧光强度的最大值相对于测定开始时刻的荧光强度的增加率作为T2R16对激动剂的应答强度。将结果示于图2。
如图2所示，仅包含Gα-T2R16质粒的细胞株显示出对水杨苷的应答。在包含T2R16-Gα质粒的细胞株中，基本上没有观测到对水杨苷的应答，无法分离显示出应答的克隆。
(2)Gα-T2R40及Gα-T2R43的稳定表达株的应答测定
对于除T2R16以外的苦味受体的亚型T2R40、T2R43，也与实施例3(1)同样地测定了稳定表达株的应答。
具体而言，与实施例1、实施例2中记载的方法同样地制备了Gα-T2R40稳定表达株(包含Gα16/Gαgust43-IRES-ssr/T2R40/V5)及Gα-T2R43稳定表达株(包含Gα16/Gαgust43-IRES-ssr/T2R43/V5)。
使用与实施例2中记载的方法相同的方法制备了Gα-T2R40稳定表达株及Gα-T2R43稳定表达株。使100μM或300μM的各激动剂(T2R40：地芬尼多，T2R43：奎宁)作用于这些细胞株，得到了添加后40秒钟的荧光强度的最大值。计算荧光强度的最大值相对于测定开始时刻的荧光强度的增加率作为T2R40、T2R43对激动剂的应答强度。将结果示于图3。与T2R40-Gα、T2R43-Gα相比，Gα-T2R40及Gα-T2R43对各激动剂显示出高应答强度。
实施例4 短暂表达细胞对苦味物质的应答测定
使用Lipofectamine(注册商标)3000将Gα-T2R16及T2R16-Gα各质粒载体0.1μg基因导入以2×104个接种于96孔板的HEK293T。在30小时培养后，使用与实施例3(1)相同的方法测定了对水杨苷的应答强度(添加水杨苷后40秒钟的荧光强度的最大值)。需要说明的是，没有进行实施例2那样的基于潮霉素B的药物抗性筛选(短暂表达细胞)。
另外，作为比较例，除T2R16-Gα表达细胞以外，也制备了以下的细胞，并测定了对水杨苷的应答。
对将Gα16/Gαgust43表达基因及ssr-T2R16-V5表达基因分别导入pcDNA3.1Hygro(+)载体而成的Gα16/Gαgust43gust表达载体和ssr-T2R16-V5表达载体以总计0.1μg同时进行基因导入并使其短暂表达的细胞(共转染)；以及
向使用与实施例2相同的方法制备的Gα16/Gαgust43稳定表达株(经过基于潮霉素B的药物抗性筛选)基因导入0.1μg的ssr-T2R16-V5表达载体、并使其短暂表达的细胞(Gαstable)。
将结果示于图4。根据图4的结果可知，在短暂表达体系中，Gα-T2R16也显示出比T2R16-Gα更高的应答强度，并且确认了比已知的短暂表达体系(共转染及Gαstable)显示出更高的应答强度。
实施例5 Gα16/Gαgust43及苦味受体T2R16的表达量
通常认为，与从5’末端起的帽依赖性翻译相比，IRES介导的mRNA的翻译是低效率的。在本实施例中，关于帽依赖性翻译和IRES依赖性翻译，调查了Gα16/Gαgust43及苦味受体T2R16的表达量。
(1)Gα16/Gαgust43的表达量
关于实施例4中制备的Gα-T2R16(本发明)、T2R16-Gα、共转染的短暂表达细胞，与实施例3的方法同样地测定了对于作为T2R非依赖性Gα16激动剂的异丙肾上腺素(3μM)的应答强度，并进行了比较。将其结果示于图5。
可以认为对于异丙肾上腺素的应答强度与Gα16的表达量成比例。如图5所示，确认了与Gα16/Gαgust43被帽依赖性翻译的Gα-T2R16、共转染相比，Gα16/Gαgust43经由IRES被翻译的T2R16-Gα的表达量低。即，表明Gα16/Gαgust43的表达量为帽依赖性＞IRES依赖性。
(2)T2R16的表达量
使用仅短暂表达T2R16-Gα、Gα-T2R16(本发明)及ssr-T2R16-V5(T2R16 single)的细胞，通过In cell ELISA法比较了T2R16的表达量。在In cell ELISA中使用了In CellELISA Kit(BOO Bioscientific公司)，在T2R16的检测中使用了识别在C末端添加的V5表位的抗V5-HRP抗体(Thermo Fisher Scientific公司)。T2R16的相对表达量通过测定HRP底物的显色在450nm的吸光度而获得。
将结果示于图6。该结果确认了，T2R16经由IRES被翻译的Gα-T2R16的T2R16表达量高于T2R16被帽依赖性翻译的T2R16-Gα及T2R16single。即表明，T2R16的表达量为帽依赖性＜IRES依赖性。在使用了与Gα16/Gαgust43相比与T2R的结合性更弱的Gα16的情况下也得到了同样的结果(未示出数据)。
因此表明，本发明的Gα-T2R16使Gα16/Gαgust43(及Gα16)、T2R16均高表达。另外，在苦味受体的T2R16以外的亚型(T2R40及T2R43)中也观察到了同样的结果(未示出数据)。
实施例6 Gα-T2R16稳定表达株的保存稳定性
在本实施例中，调查了Gα-T2R16稳定表达株在冷冻保存前后的应答强度。
与实施例2的Gα-T2R16稳定表达株同样地制备了本实施例的Gα-T2R16，作为表达载体，使用了pEAK10(Edge biosystem公司)，并且插入了“ssr/T2R16”(无V5)代替“ssr/T2R16/V5”。另外，使用1μg/mL的嘌呤霉素代替潮霉素B进行了药物抗性筛选。
作为比较例，使用了Gα16/Gαgust43稳定表达+T2R16稳定表达的稳定表达细胞株(Double stable)，其是向使用与实施例2相同方法制备的Gα16/Gαgust43稳定表达株(经过基于嘌呤霉素的药物抗性筛选)进一步基因导入5μg的ssr-T2R16表达载体，并且接着进行基于嘌呤霉素的药物抗性筛选而制备成的。
在细胞株冷冻保存前后与实施例3同样地调查了对水杨苷(1或0.1mM)的应答强度。冷冻保存中使用了CELLBANKER(日本全药工业株式会社)，在液氮中保存了1个月。在将冷冻保存的细胞恢复常温、并进行了2次以上传代后，测定了冷冻保存后的应答强度。将结果示于图7。
其结果是在Gα-T2R16稳定表达株中基本上没有确认到冷冻造成的影响。与此相对，在Double stable中，偶见冷冻后应答强度显著降低的细胞株。将结果的一例示于图7。在图7中，对于Gα-T2R16稳定表达株而言，在水杨苷浓度为1mM、0.1mM的任意情况下，应答强度的冷冻后/冷冻前的比率为0.8以上。与此相对，Double stable低于0.6(特别是在水杨苷为0.1mM的情况下，为0.4以下)。
实施例7 Gα-T2R40稳定表达株对T2R40激动剂的应答强度和对Gα激动剂的应答强度
在本实施例中，对于本发明的Gα-T2R40稳定表达株，调查了对T2R40激动剂(地芬尼多)的应答强度和对Gα激动剂(异丙肾上腺素)的应答强度的相关性。
如实施例3(2)中的记载所述，使用与实施例1、实施例2中记载的方法相同的方法制备Gα-T2R40稳定表达株，克隆了15个。对于15个克隆，将对异丙肾上腺素(10μM)及地芬尼多(300μM)的应答的相关性示于图8。其结果是得到了对于作为T2R40激动剂的地芬尼多与作为Gα16激动剂的异丙肾上腺素的应答具有高相关性。
因此，在使用本发明的构建体的方法中，可以仅通过与T2R或Gα亚基的任意蛋白相关的1次评价，就得到表达Gα亚基和T2R这两种蛋白质的希望的细胞株。相比之下，在使用现有方法的情况下，需要将表达Gα亚基和T2R各蛋白质的基因依次导入细胞，并且每次在评价各蛋白质是否稳定地表达的同时进行筛选。具体而言，在制备Gα稳定表达株进行筛选(评价1)后，导入编码T2R蛋白的基因，得到保持Gα蛋白(高)表达(评价2)、且T2R蛋白质也(高)表达(评价3)的细胞株。即，为了得到希望的细胞株，需要进行3次评价。
通过本发明，用于得到Gα-T2R40稳定表达株的操作效率显著提高。
实施例8 甜味受体T1R2/T1R3的IRES介导的表达体系1：T1R2的探讨
甜味受体是T1R2和T1R3这2种亚基的组合所形成的代谢性谷氨酸受体/代谢性信息素受体类型的G蛋白偶联受体。在本实施例中，对于甜味受体T1R2/T1R3的IRES介导的表达体系的T1R2进行了探讨。
(1)表达载体的制备
准备了人甜味受体亚基T1R2及人甜味受体亚基T1R3、以及实施例1中记载的IRES及Gα16/Gαgust43(Gα)。如以下所述，将它们插入pcDNA3.1Hygro(+)载体(Thermo FisherScientific公司)的多克隆位点，得到了各构建体。
构建体Gα-T1R2
Gα16/Gαgust43-IRES-T1R2/V5
构建体T1R2-Gα
ssr/T1R2/V5-IRES-Gα16/Gαgust43
构建体T1R3
T1R3
(2)T1R2的表达量
通过与实施例4中记载的方法相同的方法共基因导入Gα-T1R2及T1R3，得到了短暂表达的细胞株(Gα-T1R2+T1R3)。作为比较例，共基因导入T1R2-Gα及T1R3，得到了短暂表达的细胞株(T1R2-Gα+T1R3)。
通过与实施例5(2)相同的方法，利用使用了In Cell ELISA Kit(BOOBioscientific公司)的In cell ELISA法调查了T1R2的表达量。将结果示于图9。T1R2的表达量显示出“Gα-T1R2+T1R3”高于“T1R2-Gα+T1R3”的倾向。与苦味受体(T2R)的情况相同，帽依赖性＜IRES依赖性。
(3)Gα16/Gαgust43的表达量
对于“Gα-T1R2+T1R3”和“T1R2-Gα+T1R3”，通过与实施例5(1)相同的方法调查了Gα16/Gαgust43的表达量。作为Gα16激动剂的异丙肾上腺素使用了10μM。如图10所示，Gα16/Gαgust43的表达量显示出Gα-T1R2+T1R3高。与苦味受体(T2R)的情况相同，帽依赖性＞IRES依赖性。
(4)对T1R2激动剂的应答
对于“Gα-T1R2+T1R3”和“T1R2-Gα+T1R3”，调查了对T1R2激动剂的应答。添加阿斯巴甜(10mM)，得到了添加后40秒钟的荧光强度的最大值。计算荧光强度的最大值相对于测定开始时刻的荧光强度的增加率作为T1R2对激动剂的应答强度。
作为比较例，除“T1R2-Gα+T1R3”以外，还使用了“将分别包含编码T1R2、T1R3及Gα16/Gαgust43各蛋白的基因的3种载体进行共转染而得到的细胞(T1R2+T1R3+Gα)”、以及“将T1R2-Gα和T1R3-Gα进行共转染而得到的细胞(T1R2-Gα+T1R3-Gα)”。如图11所示，“Gα-T1R2+T1R3”显示出对T1R2激动剂的最高应答。
实施例9 甜味受体T1R2/T1R3的IRES介导的表达体系2：T1R3的探讨
在本实施例中，对甜味受体T1R2/T1R3的IRES介导的表达体系的T1R3进行了探讨。
(1)表达载体的制备
准备了人甜味受体亚基T1R2及人甜味受体亚基T1R3、以及实施例1中记载的IRES及Gα16/Gαgust43(Gα)。如下所示，将它们插入pcDNA3.1Hygro(+)载体(Thermo FisherScientific公司)的多克隆位点，得到了各构建体。
构建体Gα-T1R3
Gα16/Gαgust43-IRES-ssr/T1R3/V5
构建体T1R3-Gα
ssr/T1R3/V5-IRES-Gα16/Gαgust43
构建体T1R2
T1R2
(2)T1R3的表达量
通过与实施例4中记载的方法相同的方法共基因导入Gα-T1R3及T1R2，得到了短暂表达的细胞株(Gα-T1R3+T1R2)。作为比较例，将T1R3-Gα及T1R2共基因导入，得到了短暂表达的细胞株(T1R3-Gα+T1R2)。
通过与实施例5(2)相同的方法，利用使用了In Cell ELISA Kit(BOOBioscientific公司)的In cell ELISA法调查了T1R3的表达量。将结果示于图12。与“T1R3-Gα+T1R2”相比，“Gα-T1R3+T1R2”的T1R3表达量多。T1R3的表达量为帽依赖性＜IRES依赖性。
(3)Gα16/Gαgust43的表达量
对于“Gα-T1R3+T1R2”和“T1R3-Gα+T1R2”，通过与实施例5(1)相同的方法调查了Gα16/Gαgust43的表达量。作为Gα16激动剂的异丙肾上腺素使用了10μM。如图13所示，对于Gα16/Gαgust43的表达量而言，Gα-T1R3+T1R2的高，与苦味受体(T2R)的情况相同，帽依赖性＞IRES依赖性。
与实施例9(2)的结果结合表明，本发明的Gα-T1R3使T1R3、Gα16/Gαgust43均高表达。
(4)对T1R3激动剂的应答
对于“Gα-T1R3+T1R2”和“T1R3-Gα+T1R2”，调查了对T1R3激动剂的应答。添加甜蜜素(10mM)，得到了添加后40秒钟的荧光强度的最大值。计算荧光强度的最大值相对于测定开始时刻的荧光强度的增加率作为T1R3对激动剂的应答强度。
作为比较例，除“T1R3-Gα+T1R2”以外，还使用了“将分别包含编码T1R2、T1R3及Gα16/Gαgust43各蛋白的基因的3种载体进行共转染而得到的细胞”、以及“将T1R2-Gα和T1R3-Gα进行共转染而得到的细胞”。如图14所示，“Gα-T1R3+T1R2”显示出对T1R3激动剂的最高应答。
实施例10 IRES介导的蛋白质的表达
为了调查IRES对蛋白质表达量施加的效果，使除GPCR蛋白以外的蛋白质在IRES的上游及下游表达。作为蛋白质，使用了绿色荧光蛋白(EmGFP)(碱基序列：序列号78(GenBank的Accession号EU056363.1)；氨基酸序列：序列号79)。制备在pcDNA载体中包含以下A-D的核酸序列的构建体，基因导入至细胞株HEK293T，使其短暂表达。
A：ssr-EmGFP-IRES-Gα
B：EmGFP-IRES-Gα
C：Gα-IRES-ssr-EmGFP
D：Gα-IRES-EmGFP
对照：不包含插入基因的pcDNA载体
在487nm波长下激发，测定了509nm波长的荧光强度。荧光强度与EmGFP的表达量成比例。将结果示于图15。EmGFP基因配置在IRES上游的情况(A、B)与配置在下游的情况(C、D)相比，EmGFP蛋白的表达量高。EmGFP蛋白的表达量与Gα蛋白同样地为帽依赖性＞IRES依赖性。
实施例11 短暂表达pEAK10-T2R16-Gα及pEAK10-Gα-T2R16的细胞中的T2R16表达量
在本实施例中，对导入pEAK10-IRES-T2R16-Gα及pEAK10-Gα-IRES-T 2R16并使其短暂表达的HEL293T细胞中的T2R16表达量进行了调查。以下，在实施例11～15中，有时省略“IRES”的记载。
将编码T2R16-IRES-Gα、Gα-IRES-T2R16的基因序列亚克隆至pEAK10载体(Edgebiosystem公司)，制备了表达载体pEAK10-T2R16-Gα及pEAK10-Gα-T2R16。pEAK10载体是包含EF1α启动子及嘌呤霉素抗性基因的质粒载体。通过与实施例4相同的方法将制备的表达载体导入HEK293T细胞，制备了使其短暂表达的细胞。
使用与实施例5(2)相同的方法，利用In cell ELISA法评价了短暂表达细胞的T2R16的表达量。作为对照，使用导入了未插入基因的pEAK表达载体的HEK293T细胞。在检测中，与实施例5(2)同样地使用了识别在C末端添加的V5表位的抗V5-HRP抗体(ThermoFisher Scientific公司)。
如图16所示，导入了表达载体pEAK10-Gα-T2Rl6的细胞显示出比导入了表达载体pEAK10-T2R16-Gα的细胞更高的T2R16表达量。由此表明，本发明的效果不受启动子、非翻译区域这样的载体固有基因序列的影响。
实施例12 短暂表达细胞对苦味物质的应答测定(2)
在本实施例中，关于7种T2R亚型(苦味受体)，进行了短暂表达细胞对苦味物质的应答测定。
代替实施例4中编码Gα-T2R16的T2R16的基因，制备了包含编码表5所示的7种T2R亚型的各基因的7种表达载体，通过与实施例4相同的方法，测定了短暂表达细胞对已知各亚型的激动剂(表5)的应答。
[表5]
亚型 激动剂 添加浓度
T2R4 苦龙苷(Amarogentin) 300uM
T2R8 苯甲地那铵(Denatonium benzoate) 300uM
T2R9 氧氟沙星(Ofloxacin) 100uM
T2R10 氯喹(Chloroquine) 3mM
T2R13 地芬尼多(Diphenidole) 100uM
T2R20 色甘酸(Cromolyn) 1mM
T2R39 氯喹(Chlorquinine) 1mM
其结果是，任意的T2R亚型均显示出对激动剂的应答(图17)。
实施例13 稳定表达细胞对苦味物质的应答测定(2)
在本实施例中，关于T2R38亚型(苦味受体)，进行了稳定表达细胞对苦味物质的应答测定。
代替实施例1、2中编码Gα-T2R16的T2R16的基因，制备了包含编码T2R38亚型(苦味受体)的基因的表达载体Gα-T2R38，通过与实施例1、2相同的方法制备了稳定表达株。
接着，使用与实施例3相同的方法测定了T2R38对已知激动剂6-正丙基硫尿嘧啶(1000μM、300μM)的应答。作为对照，使用了未整合表达载体Gα-T2R38的细胞株(HEK293T)。其结果是，对6-正丙基硫尿嘧啶(1000μM、300μM任意情况)显示出应答(图18)。
实施例14 苦味受体在短暂表达细胞中的表达量
在本实施例中，对14种T2R亚型(苦味受体)在短暂表达细胞中的表达量进行了调查。
代替实施例4中编码Gα-T2R16的T2R16的基因，制作了包含编码表6所示的14种T2R亚型的各基因的基因的14种表达载体，通过与实施例4相同的方法制备了分别短暂表达各T2R及Gα的细胞。
[表6]
Figure BDA0002463519700000381
接下来，通过使用与实施例5(2)相同方法的In cell ELISA法测定了各细胞的T2R的表达量。将得到的各T2R的表达量与实施例12中确认到对已知激动剂的应答的Gα-T2R4的短暂表达细胞的T2R4表达量进行了比较。其结果是，14种全部显示出T2R4以上的T2R表达量(图19)。该结果表明，14种T2R全部具有用于进行应答测定的足够的T2R表达量。
实施例15 嗅觉受体在短暂表达细胞中的应答测定和表达量
在本实施例中，对嗅觉受体(OR3A1)在短暂表达细胞中的应答测定和表达量进行了调查。
通过与实施例1相同的方法，制备了在OR3A1的N末端添加有人视紫红质的N末端21个氨基酸(Rho)的Rho-OR3A1、以及将编码Gαolf的基因与IRES一起导入pcDNA载体而成的表达载体OR3A1-Gαolf及Gαolf-OR3A1。使用这些表达载体，通过与实施例4相同的方法制备了在HEK293T中短暂表达的细胞。作为对照，使用了将OR3A1、Gαolf各基因分别导入pcDNA并共基因导入至HEK293T而成的细胞。
接着，在制备的细胞上添加对OR3A1为已知激动剂的新洋茉莉醛(helional)(100μM、30μM)。在添加新洋茉莉醛20分钟后，通过使用了cAMP-GloMax assay kit(Promega)的发光测定检测了伴随OR3A1应答产生的cAMP的量。其结果表明，在导入了表达载体Gαolf-OR3A1的细胞中，随100μM新洋茉莉醛的添加，cAMP增加。在导入了表达载体OR3A1-Gαolf的情况、分别导入了OR3A1、Gαolf各基因的情况下，均未观察到伴随新洋茉莉醛添加的应答(cAMP的增加)(图20)。
另外，通过使用了抗Rho抗体(Merck)及抗Gαolf抗体(SANTA CRUZ)的In CellELISA对Rho-OR3A1和Gαolf的表达量进行了比较。作为对照，使用导入了未插入任何基因的pcDNA的HEK293T细胞。其结果是，与导入了OR3A1-Gαolf的细胞相比，导入了Gαolf-OR3A1的细胞显示出高的Gαolf、OR3A1表达量(图21)。
序列表
<110> 日本烟草产业株式会社(JAPAN TOBACCO INC.)
<120> 用于表达G蛋白偶联受体或其亚基的构建体及其用途
<130> FA0092-18121
<150> JP2017-204687
<151> 2017-10-23
<160> 81
<170> PatentIn version 3.5
<210> 1
<211> 900
<212> DNA
<213> 智人
<220>
<221> CDS
<222> (1)..(900)
<400> 1
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245 250 255
ttc atc ttt ctg ttc ttc atc ctt gtg att ggt ata tac cct tct gga 816
Phe Ile Phe Leu Phe Phe Ile Leu Val Ile Gly Ile Tyr Pro Ser Gly
260 265 270
cac tct ctc atc tta att tta gga aat cct aaa ttg aaa caa aat gca 864
His Ser Leu Ile Leu Ile Leu Gly Asn Pro Lys Leu Lys Gln Asn Ala
275 280 285
aaa aag ttc ctc ctc cac agt aag tgc tgt cag tga 900
Lys Lys Phe Leu Leu His Ser Lys Cys Cys Gln
290 295
<210> 2
<211> 299
<212> PRT
<213> 智人
<400> 2
Met Leu Glu Ser His Leu Ile Ile Tyr Phe Leu Leu Ala Val Ile Gln
1 5 10 15
Phe Leu Leu Gly Ile Phe Thr Asn Gly Ile Ile Val Val Val Asn Gly
20 25 30
Ile Asp Leu Ile Lys His Arg Lys Met Ala Pro Leu Asp Leu Leu Leu
35 40 45
Ser Cys Leu Ala Val Ser Arg Ile Phe Leu Gln Leu Phe Ile Phe Tyr
50 55 60
Val Asn Val Ile Val Ile Phe Phe Ile Glu Phe Ile Met Cys Ser Ala
65 70 75 80
Asn Cys Ala Ile Leu Leu Phe Ile Asn Glu Leu Glu Leu Trp Leu Ala
85 90 95
Thr Trp Leu Gly Val Phe Tyr Cys Ala Lys Val Ala Ser Val Arg His
100 105 110
Pro Leu Phe Ile Trp Leu Lys Met Arg Ile Ser Lys Leu Val Pro Trp
115 120 125
Met Ile Leu Gly Ser Leu Leu Tyr Val Ser Met Ile Cys Val Phe His
130 135 140
Ser Lys Tyr Ala Gly Phe Met Val Pro Tyr Phe Leu Arg Lys Phe Phe
145 150 155 160
Ser Gln Asn Ala Thr Ile Gln Lys Glu Asp Thr Leu Ala Ile Gln Ile
165 170 175
Phe Ser Phe Val Ala Glu Phe Ser Val Pro Leu Leu Ile Phe Leu Phe
180 185 190
Ala Val Leu Leu Leu Ile Phe Ser Leu Gly Arg His Thr Arg Gln Met
195 200 205
Arg Asn Thr Val Ala Gly Ser Arg Val Pro Gly Arg Gly Ala Pro Ile
210 215 220
Ser Ala Leu Leu Ser Ile Leu Ser Phe Leu Ile Leu Tyr Phe Ser His
225 230 235 240
Cys Met Ile Lys Val Phe Leu Ser Ser Leu Lys Phe His Ile Arg Arg
245 250 255
Phe Ile Phe Leu Phe Phe Ile Leu Val Ile Gly Ile Tyr Pro Ser Gly
260 265 270
His Ser Leu Ile Leu Ile Leu Gly Asn Pro Lys Leu Lys Gln Asn Ala
275 280 285
Lys Lys Phe Leu Leu His Ser Lys Cys Cys Gln
290 295
<210> 3
<211> 951
<212> DNA
<213> 智人
<220>
<221> CDS
<222> (1)..(951)
<400> 3
atg atg gga ctc acc gag ggg gtg ttc ctg att ctg tct ggc act cag 48
Met Met Gly Leu Thr Glu Gly Val Phe Leu Ile Leu Ser Gly Thr Gln
1 5 10 15
ttc aca ctg gga att ctg gtc aat tgt ttc att gag ttg gtc aat ggt 96
Phe Thr Leu Gly Ile Leu Val Asn Cys Phe Ile Glu Leu Val Asn Gly
20 25 30
agc agc tgg ttc aag acc aag aga atg tct ttg tct gac ttc atc atc 144
Ser Ser Trp Phe Lys Thr Lys Arg Met Ser Leu Ser Asp Phe Ile Ile
35 40 45
acc acc ctg gca ctc ttg agg atc att ctg ctg tgt att atc ttg act 192
Thr Thr Leu Ala Leu Leu Arg Ile Ile Leu Leu Cys Ile Ile Leu Thr
50 55 60
gat agt ttt tta ata gaa ttc tct ccc aac aca cat gat tca ggg ata 240
Asp Ser Phe Leu Ile Glu Phe Ser Pro Asn Thr His Asp Ser Gly Ile
65 70 75 80
ata atg caa att att gat gtt tcc tgg aca ttt aca aac cat ctg agc 288
Ile Met Gln Ile Ile Asp Val Ser Trp Thr Phe Thr Asn His Leu Ser
85 90 95
att tgg ctt gcc acc tgt ctt ggt gtc ctc tac tgc ctg aaa atc gcc 336
Ile Trp Leu Ala Thr Cys Leu Gly Val Leu Tyr Cys Leu Lys Ile Ala
100 105 110
agt ttc tct cac ccc aca ttc ctc tgg ctc aag tgg aga gtt tct agg 384
Ser Phe Ser His Pro Thr Phe Leu Trp Leu Lys Trp Arg Val Ser Arg
115 120 125
gtg atg gta tgg atg ctg ttg ggt gca ctg ctc tta tcc tgt ggt agt 432
Val Met Val Trp Met Leu Leu Gly Ala Leu Leu Leu Ser Cys Gly Ser
130 135 140
acc gca tct ctg atc aat gag ttt aag ctc tat tct gtc ttt agg gga 480
Thr Ala Ser Leu Ile Asn Glu Phe Lys Leu Tyr Ser Val Phe Arg Gly
145 150 155 160
att gag gcc acc agg aat gtg act gaa cac ttc aga aag aag agg agt 528
Ile Glu Ala Thr Arg Asn Val Thr Glu His Phe Arg Lys Lys Arg Ser
165 170 175
gag tat tat ctg atc cat gtt ctt ggg act ctg tgg tac ctg cct ccc 576
Glu Tyr Tyr Leu Ile His Val Leu Gly Thr Leu Trp Tyr Leu Pro Pro
180 185 190
tta att gtg tcc ctg gcc tcc tac tct ttg ctc atc ttc tcc ctg ggg 624
Leu Ile Val Ser Leu Ala Ser Tyr Ser Leu Leu Ile Phe Ser Leu Gly
195 200 205
agg cac aca cgg cag atg ctg caa aat ggg aca agc tcc aga gat cca 672
Arg His Thr Arg Gln Met Leu Gln Asn Gly Thr Ser Ser Arg Asp Pro
210 215 220
acc act gag gcc cac aag agg gcc atc aga atc atc ctt tcc ttc ttc 720
Thr Thr Glu Ala His Lys Arg Ala Ile Arg Ile Ile Leu Ser Phe Phe
225 230 235 240
ttt ctc ttc tta ctt tac ttt ctt gct ttc tta att gca tca ttt ggt 768
Phe Leu Phe Leu Leu Tyr Phe Leu Ala Phe Leu Ile Ala Ser Phe Gly
245 250 255
aat ttc cta cca aaa acc aag atg gct aag atg att ggc gaa gta atg 816
Asn Phe Leu Pro Lys Thr Lys Met Ala Lys Met Ile Gly Glu Val Met
260 265 270
aca atg ttt tat cct gct ggc cac tca ttt att ctc att ctg ggg aac 864
Thr Met Phe Tyr Pro Ala Gly His Ser Phe Ile Leu Ile Leu Gly Asn
275 280 285
agt aag ctg aag cag aca ttt gta gtg atg ctc cgg tgt gag tct ggt 912
Ser Lys Leu Lys Gln Thr Phe Val Val Met Leu Arg Cys Glu Ser Gly
290 295 300
cat ctg aag cct gga tcc aag gga ccc att ttc tct tag 951
His Leu Lys Pro Gly Ser Lys Gly Pro Ile Phe Ser
305 310 315
<210> 4
<211> 316
<212> PRT
<213> 智人
<400> 4
Met Met Gly Leu Thr Glu Gly Val Phe Leu Ile Leu Ser Gly Thr Gln
1 5 10 15
Phe Thr Leu Gly Ile Leu Val Asn Cys Phe Ile Glu Leu Val Asn Gly
20 25 30
Ser Ser Trp Phe Lys Thr Lys Arg Met Ser Leu Ser Asp Phe Ile Ile
35 40 45
Thr Thr Leu Ala Leu Leu Arg Ile Ile Leu Leu Cys Ile Ile Leu Thr
50 55 60
Asp Ser Phe Leu Ile Glu Phe Ser Pro Asn Thr His Asp Ser Gly Ile
65 70 75 80
Ile Met Gln Ile Ile Asp Val Ser Trp Thr Phe Thr Asn His Leu Ser
85 90 95
Ile Trp Leu Ala Thr Cys Leu Gly Val Leu Tyr Cys Leu Lys Ile Ala
100 105 110
Ser Phe Ser His Pro Thr Phe Leu Trp Leu Lys Trp Arg Val Ser Arg
115 120 125
Val Met Val Trp Met Leu Leu Gly Ala Leu Leu Leu Ser Cys Gly Ser
130 135 140
Thr Ala Ser Leu Ile Asn Glu Phe Lys Leu Tyr Ser Val Phe Arg Gly
145 150 155 160
Ile Glu Ala Thr Arg Asn Val Thr Glu His Phe Arg Lys Lys Arg Ser
165 170 175
Glu Tyr Tyr Leu Ile His Val Leu Gly Thr Leu Trp Tyr Leu Pro Pro
180 185 190
Leu Ile Val Ser Leu Ala Ser Tyr Ser Leu Leu Ile Phe Ser Leu Gly
195 200 205
Arg His Thr Arg Gln Met Leu Gln Asn Gly Thr Ser Ser Arg Asp Pro
210 215 220
Thr Thr Glu Ala His Lys Arg Ala Ile Arg Ile Ile Leu Ser Phe Phe
225 230 235 240
Phe Leu Phe Leu Leu Tyr Phe Leu Ala Phe Leu Ile Ala Ser Phe Gly
245 250 255
Asn Phe Leu Pro Lys Thr Lys Met Ala Lys Met Ile Gly Glu Val Met
260 265 270
Thr Met Phe Tyr Pro Ala Gly His Ser Phe Ile Leu Ile Leu Gly Asn
275 280 285
Ser Lys Leu Lys Gln Thr Phe Val Val Met Leu Arg Cys Glu Ser Gly
290 295 300
His Leu Lys Pro Gly Ser Lys Gly Pro Ile Phe Ser
305 310 315
<210> 5
<211> 900
<212> DNA
<213> 智人
<220>
<221> CDS
<222> (1)..(900)
<400> 5
atg ctt cgg tta ttc tat ttc tct gct att att gcc tca gtt att tta 48
Met Leu Arg Leu Phe Tyr Phe Ser Ala Ile Ile Ala Ser Val Ile Leu
1 5 10 15
aat ttt gta gga atc att atg aat ctg ttt att aca gtg gtc aat tgc 96
Asn Phe Val Gly Ile Ile Met Asn Leu Phe Ile Thr Val Val Asn Cys
20 25 30
aaa act tgg gtc aaa agc cat aga atc tcc tct tct gat agg att ctg 144
Lys Thr Trp Val Lys Ser His Arg Ile Ser Ser Ser Asp Arg Ile Leu
35 40 45
ttc agc ctg ggc atc acc agg ttt ctt atg ctg gga cta ttt ctg gtg 192
Phe Ser Leu Gly Ile Thr Arg Phe Leu Met Leu Gly Leu Phe Leu Val
50 55 60
aac acc atc tac ttc gtc tct tca aat acg gaa agg tca gtc tac ctg 240
Asn Thr Ile Tyr Phe Val Ser Ser Asn Thr Glu Arg Ser Val Tyr Leu
65 70 75 80
tct gct ttt ttt gtg ttg tgt ttc atg ttt ttg gac tcg agc agt gtc 288
Ser Ala Phe Phe Val Leu Cys Phe Met Phe Leu Asp Ser Ser Ser Val
85 90 95
tgg ttt gtg acc ttg ctc aat atc ttg tac tgt gtg aag att act aac 336
Trp Phe Val Thr Leu Leu Asn Ile Leu Tyr Cys Val Lys Ile Thr Asn
100 105 110
ttc caa cac tca gtg ttt ctc ctg ctg aag cgg aat atc tcc cca aag 384
Phe Gln His Ser Val Phe Leu Leu Leu Lys Arg Asn Ile Ser Pro Lys
115 120 125
atc ccc agg ctg ctg ctg gcc tgt gtg ctg att tct gct ttc acc act 432
Ile Pro Arg Leu Leu Leu Ala Cys Val Leu Ile Ser Ala Phe Thr Thr
130 135 140
tgc ctg tac atc acg ctt agc cag gca tca cct ttt cct gaa ctt gtg 480
Cys Leu Tyr Ile Thr Leu Ser Gln Ala Ser Pro Phe Pro Glu Leu Val
145 150 155 160
act acg aga aat aac aca tca ttt aat atc agt gag ggc atc ttg tct 528
Thr Thr Arg Asn Asn Thr Ser Phe Asn Ile Ser Glu Gly Ile Leu Ser
165 170 175
tta gtg gtt tct ttg gtc ttg agc tca tct ctc cag ttc atc att aat 576
Leu Val Val Ser Leu Val Leu Ser Ser Ser Leu Gln Phe Ile Ile Asn
180 185 190
gtg act tct gct tcc ttg cta ata cac tcc ttg agg aga cat ata cag 624
Val Thr Ser Ala Ser Leu Leu Ile His Ser Leu Arg Arg His Ile Gln
195 200 205
aag atg cag aaa aat gcc act ggt ttc tgg aat ccc cag acg gaa gct 672
Lys Met Gln Lys Asn Ala Thr Gly Phe Trp Asn Pro Gln Thr Glu Ala
210 215 220
cat gta ggt gct atg aag ctg atg gtc tat ttc ctc atc ctc tac att 720
His Val Gly Ala Met Lys Leu Met Val Tyr Phe Leu Ile Leu Tyr Ile
225 230 235 240
cca tat tca gtt gct acc ctg gtc cag tat ctc ccc ttt tat gca ggg 768
Pro Tyr Ser Val Ala Thr Leu Val Gln Tyr Leu Pro Phe Tyr Ala Gly
245 250 255
atg gat atg ggg acc aaa tcc att tgt ctg att ttt gcc acc ctt tac 816
Met Asp Met Gly Thr Lys Ser Ile Cys Leu Ile Phe Ala Thr Leu Tyr
260 265 270
tct cca gga cat tct gtt ctc att att atc aca cat cct aaa ctg aaa 864
Ser Pro Gly His Ser Val Leu Ile Ile Ile Thr His Pro Lys Leu Lys
275 280 285
aca aca gca aag aag att ctt tgt ttc aaa aaa tag 900
Thr Thr Ala Lys Lys Ile Leu Cys Phe Lys Lys
290 295
<210> 6
<211> 299
<212> PRT
<213> 智人
<400> 6
Met Leu Arg Leu Phe Tyr Phe Ser Ala Ile Ile Ala Ser Val Ile Leu
1 5 10 15
Asn Phe Val Gly Ile Ile Met Asn Leu Phe Ile Thr Val Val Asn Cys
20 25 30
Lys Thr Trp Val Lys Ser His Arg Ile Ser Ser Ser Asp Arg Ile Leu
35 40 45
Phe Ser Leu Gly Ile Thr Arg Phe Leu Met Leu Gly Leu Phe Leu Val
50 55 60
Asn Thr Ile Tyr Phe Val Ser Ser Asn Thr Glu Arg Ser Val Tyr Leu
65 70 75 80
Ser Ala Phe Phe Val Leu Cys Phe Met Phe Leu Asp Ser Ser Ser Val
85 90 95
Trp Phe Val Thr Leu Leu Asn Ile Leu Tyr Cys Val Lys Ile Thr Asn
100 105 110
Phe Gln His Ser Val Phe Leu Leu Leu Lys Arg Asn Ile Ser Pro Lys
115 120 125
Ile Pro Arg Leu Leu Leu Ala Cys Val Leu Ile Ser Ala Phe Thr Thr
130 135 140
Cys Leu Tyr Ile Thr Leu Ser Gln Ala Ser Pro Phe Pro Glu Leu Val
145 150 155 160
Thr Thr Arg Asn Asn Thr Ser Phe Asn Ile Ser Glu Gly Ile Leu Ser
165 170 175
Leu Val Val Ser Leu Val Leu Ser Ser Ser Leu Gln Phe Ile Ile Asn
180 185 190
Val Thr Ser Ala Ser Leu Leu Ile His Ser Leu Arg Arg His Ile Gln
195 200 205
Lys Met Gln Lys Asn Ala Thr Gly Phe Trp Asn Pro Gln Thr Glu Ala
210 215 220
His Val Gly Ala Met Lys Leu Met Val Tyr Phe Leu Ile Leu Tyr Ile
225 230 235 240
Pro Tyr Ser Val Ala Thr Leu Val Gln Tyr Leu Pro Phe Tyr Ala Gly
245 250 255
Met Asp Met Gly Thr Lys Ser Ile Cys Leu Ile Phe Ala Thr Leu Tyr
260 265 270
Ser Pro Gly His Ser Val Leu Ile Ile Ile Thr His Pro Lys Leu Lys
275 280 285
Thr Thr Ala Lys Lys Ile Leu Cys Phe Lys Lys
290 295
<210> 7
<211> 900
<212> DNA
<213> 智人
<220>
<221> CDS
<222> (1)..(900)
<400> 7
atg ctg agc gct ggc cta gga ctg ctg atg ctg gtg gca gtg gtt gaa 48
Met Leu Ser Ala Gly Leu Gly Leu Leu Met Leu Val Ala Val Val Glu
1 5 10 15
ttt ctc atc ggt tta att gga aat gga agc ctg gtg gtc tgg agt ttt 96
Phe Leu Ile Gly Leu Ile Gly Asn Gly Ser Leu Val Val Trp Ser Phe
20 25 30
aga gaa tgg atc aga aaa ttc aac tgg tcc tca tat aac ctc att atc 144
Arg Glu Trp Ile Arg Lys Phe Asn Trp Ser Ser Tyr Asn Leu Ile Ile
35 40 45
ctg ggc ctg gct ggc tgc cga ttt ctc ctg cag tgg ctg atc att ttg 192
Leu Gly Leu Ala Gly Cys Arg Phe Leu Leu Gln Trp Leu Ile Ile Leu
50 55 60
gac tta agc ttg ttt cca ctt ttc cag agc agc cgt tgg ctt cgc tat 240
Asp Leu Ser Leu Phe Pro Leu Phe Gln Ser Ser Arg Trp Leu Arg Tyr
65 70 75 80
ctt agt atc ttc tgg gtc ctg gta agc cag gcc agc tta tgg ttt gcc 288
Leu Ser Ile Phe Trp Val Leu Val Ser Gln Ala Ser Leu Trp Phe Ala
85 90 95
acc ttc ctc agt gtc ttc tat tgc aag aag atc acg acc ttc gat cgc 336
Thr Phe Leu Ser Val Phe Tyr Cys Lys Lys Ile Thr Thr Phe Asp Arg
100 105 110
ccg gcc tac ttg tgg ctg aag cag agg gcc tat aac ctg agt ctc tgg 384
Pro Ala Tyr Leu Trp Leu Lys Gln Arg Ala Tyr Asn Leu Ser Leu Trp
115 120 125
tgc ctt ctg ggc tac ttt ata atc aat ttg tta ctt aca gtc caa att 432
Cys Leu Leu Gly Tyr Phe Ile Ile Asn Leu Leu Leu Thr Val Gln Ile
130 135 140
ggc tta aca ttc tat cat cct ccc caa gga aac agc agc att cgg tat 480
Gly Leu Thr Phe Tyr His Pro Pro Gln Gly Asn Ser Ser Ile Arg Tyr
145 150 155 160
ccc ttt gaa agc tgg cag tac ctg tat gca ttt cag ctc aat tca gga 528
Pro Phe Glu Ser Trp Gln Tyr Leu Tyr Ala Phe Gln Leu Asn Ser Gly
165 170 175
agt tat ttg cct tta gtg gtg ttt ctt gtt tcc tct ggg atg ctg att 576
Ser Tyr Leu Pro Leu Val Val Phe Leu Val Ser Ser Gly Met Leu Ile
180 185 190
gtc tct ttg tat aca cac cac aag aag atg aag gtc cat tca gct ggt 624
Val Ser Leu Tyr Thr His His Lys Lys Met Lys Val His Ser Ala Gly
195 200 205
agg agg gat gtc cgg gcc aag gct cac atc act gcg ctg aag tcc ttg 672
Arg Arg Asp Val Arg Ala Lys Ala His Ile Thr Ala Leu Lys Ser Leu
210 215 220
ggc tgc ttc ctc tta ctt cac ctg gtt tat atc atg gcc agc ccc ttc 720
Gly Cys Phe Leu Leu Leu His Leu Val Tyr Ile Met Ala Ser Pro Phe
225 230 235 240
tcc atc acc tcc aag act tat cct cct gat ctc acc agt gtc ttc atc 768
Ser Ile Thr Ser Lys Thr Tyr Pro Pro Asp Leu Thr Ser Val Phe Ile
245 250 255
tgg gag aca ctc atg gca gcc tat cct tct ctt cat tct ctc ata ttg 816
Trp Glu Thr Leu Met Ala Ala Tyr Pro Ser Leu His Ser Leu Ile Leu
260 265 270
atc atg ggg att cct agg gtg aag cag act tgt cag aag atc ctg tgg 864
Ile Met Gly Ile Pro Arg Val Lys Gln Thr Cys Gln Lys Ile Leu Trp
275 280 285
aag aca gtg tgt gct cgg aga tgc tgg ggc cca tga 900
Lys Thr Val Cys Ala Arg Arg Cys Trp Gly Pro
290 295
<210> 8
<211> 299
<212> PRT
<213> 智人
<400> 8
Met Leu Ser Ala Gly Leu Gly Leu Leu Met Leu Val Ala Val Val Glu
1 5 10 15
Phe Leu Ile Gly Leu Ile Gly Asn Gly Ser Leu Val Val Trp Ser Phe
20 25 30
Arg Glu Trp Ile Arg Lys Phe Asn Trp Ser Ser Tyr Asn Leu Ile Ile
35 40 45
Leu Gly Leu Ala Gly Cys Arg Phe Leu Leu Gln Trp Leu Ile Ile Leu
50 55 60
Asp Leu Ser Leu Phe Pro Leu Phe Gln Ser Ser Arg Trp Leu Arg Tyr
65 70 75 80
Leu Ser Ile Phe Trp Val Leu Val Ser Gln Ala Ser Leu Trp Phe Ala
85 90 95
Thr Phe Leu Ser Val Phe Tyr Cys Lys Lys Ile Thr Thr Phe Asp Arg
100 105 110
Pro Ala Tyr Leu Trp Leu Lys Gln Arg Ala Tyr Asn Leu Ser Leu Trp
115 120 125
Cys Leu Leu Gly Tyr Phe Ile Ile Asn Leu Leu Leu Thr Val Gln Ile
130 135 140
Gly Leu Thr Phe Tyr His Pro Pro Gln Gly Asn Ser Ser Ile Arg Tyr
145 150 155 160
Pro Phe Glu Ser Trp Gln Tyr Leu Tyr Ala Phe Gln Leu Asn Ser Gly
165 170 175
Ser Tyr Leu Pro Leu Val Val Phe Leu Val Ser Ser Gly Met Leu Ile
180 185 190
Val Ser Leu Tyr Thr His His Lys Lys Met Lys Val His Ser Ala Gly
195 200 205
Arg Arg Asp Val Arg Ala Lys Ala His Ile Thr Ala Leu Lys Ser Leu
210 215 220
Gly Cys Phe Leu Leu Leu His Leu Val Tyr Ile Met Ala Ser Pro Phe
225 230 235 240
Ser Ile Thr Ser Lys Thr Tyr Pro Pro Asp Leu Thr Ser Val Phe Ile
245 250 255
Trp Glu Thr Leu Met Ala Ala Tyr Pro Ser Leu His Ser Leu Ile Leu
260 265 270
Ile Met Gly Ile Pro Arg Val Lys Gln Thr Cys Gln Lys Ile Leu Trp
275 280 285
Lys Thr Val Cys Ala Arg Arg Cys Trp Gly Pro
290 295
<210> 9
<211> 957
<212> DNA
<213> 智人
<220>
<221> CDS
<222> (1)..(957)
<400> 9
atg gca gat aaa gtg cag act act tta ttg ttc tta gca gtt gga gag 48
Met Ala Asp Lys Val Gln Thr Thr Leu Leu Phe Leu Ala Val Gly Glu
1 5 10 15
ttt tca gtg ggg atc tta ggg aat gca ttc att gga ttg gta aac tgc 96
Phe Ser Val Gly Ile Leu Gly Asn Ala Phe Ile Gly Leu Val Asn Cys
20 25 30
atg gac tgg gtc aag aag agg aaa att gcc tcc att gat tta atc ctc 144
Met Asp Trp Val Lys Lys Arg Lys Ile Ala Ser Ile Asp Leu Ile Leu
35 40 45
aca agt ctg gcc ata tcc aga att tgt cta ttg tgc gta ata cta tta 192
Thr Ser Leu Ala Ile Ser Arg Ile Cys Leu Leu Cys Val Ile Leu Leu
50 55 60
gat tgt ttt ata ttg gtg cta tat cca gat gtc tat gcc act ggt aaa 240
Asp Cys Phe Ile Leu Val Leu Tyr Pro Asp Val Tyr Ala Thr Gly Lys
65 70 75 80
gaa atg aga atc att gac ttc ttc tgg aca cta acc aat cat tta agt 288
Glu Met Arg Ile Ile Asp Phe Phe Trp Thr Leu Thr Asn His Leu Ser
85 90 95
atc tgg ttt gca acc tgc ctc agc att tac tat ttc ttc aag ata ggt 336
Ile Trp Phe Ala Thr Cys Leu Ser Ile Tyr Tyr Phe Phe Lys Ile Gly
100 105 110
aat ttc ttt cac cca ctt ttc ctc tgg atg aag tgg aga att gac agg 384
Asn Phe Phe His Pro Leu Phe Leu Trp Met Lys Trp Arg Ile Asp Arg
115 120 125
gtg att tcc tgg att cta ctg ggg tgc gtg gtt ctc tct gtg ttt att 432
Val Ile Ser Trp Ile Leu Leu Gly Cys Val Val Leu Ser Val Phe Ile
130 135 140
agc ctt cca gcc act gag aat ttg aac gct gat ttc agg ttt tgt gtg 480
Ser Leu Pro Ala Thr Glu Asn Leu Asn Ala Asp Phe Arg Phe Cys Val
145 150 155 160
aag gca aag agg aaa aca aac tta act tgg agt tgc aga gta aat aaa 528
Lys Ala Lys Arg Lys Thr Asn Leu Thr Trp Ser Cys Arg Val Asn Lys
165 170 175
act caa cat gct tct acc aag tta ttt ctc aac ctg gca acg ctg ctc 576
Thr Gln His Ala Ser Thr Lys Leu Phe Leu Asn Leu Ala Thr Leu Leu
180 185 190
ccc ttt tgt gtg tgc cta atg tcc ttt ttc ctc ttg atc ctc tcc ctg 624
Pro Phe Cys Val Cys Leu Met Ser Phe Phe Leu Leu Ile Leu Ser Leu
195 200 205
cgg aga cat atc agg cga atg cag ctc agt gcc aca ggg tgc aga gac 672
Arg Arg His Ile Arg Arg Met Gln Leu Ser Ala Thr Gly Cys Arg Asp
210 215 220
ccc agc aca gaa gcc cat gtg aga gcc ctg aaa gct gtc att tcc ttc 720
Pro Ser Thr Glu Ala His Val Arg Ala Leu Lys Ala Val Ile Ser Phe
225 230 235 240
ctt ctc ctc ttt att gcc tac tat ttg tcc ttt ctc att gcc acc tcc 768
Leu Leu Leu Phe Ile Ala Tyr Tyr Leu Ser Phe Leu Ile Ala Thr Ser
245 250 255
agc tac ttt atg cca gag acg gaa tta gct gtg att ttt ggt gag tcc 816
Ser Tyr Phe Met Pro Glu Thr Glu Leu Ala Val Ile Phe Gly Glu Ser
260 265 270
ata gct cta atc tac ccc tca agt cat tca ttt atc cta ata ctg ggg 864
Ile Ala Leu Ile Tyr Pro Ser Ser His Ser Phe Ile Leu Ile Leu Gly
275 280 285
aac aat aaa tta aga cat gca tct cta aag gtg att tgg aaa gta atg 912
Asn Asn Lys Leu Arg His Ala Ser Leu Lys Val Ile Trp Lys Val Met
290 295 300
tct att cta aaa gga aga aaa ttc caa caa cat aaa caa atc tga 957
Ser Ile Leu Lys Gly Arg Lys Phe Gln Gln His Lys Gln Ile
305 310 315
<210> 10
<211> 318
<212> PRT
<213> 智人
<400> 10
Met Ala Asp Lys Val Gln Thr Thr Leu Leu Phe Leu Ala Val Gly Glu
1 5 10 15
Phe Ser Val Gly Ile Leu Gly Asn Ala Phe Ile Gly Leu Val Asn Cys
20 25 30
Met Asp Trp Val Lys Lys Arg Lys Ile Ala Ser Ile Asp Leu Ile Leu
35 40 45
Thr Ser Leu Ala Ile Ser Arg Ile Cys Leu Leu Cys Val Ile Leu Leu
50 55 60
Asp Cys Phe Ile Leu Val Leu Tyr Pro Asp Val Tyr Ala Thr Gly Lys
65 70 75 80
Glu Met Arg Ile Ile Asp Phe Phe Trp Thr Leu Thr Asn His Leu Ser
85 90 95
Ile Trp Phe Ala Thr Cys Leu Ser Ile Tyr Tyr Phe Phe Lys Ile Gly
100 105 110
Asn Phe Phe His Pro Leu Phe Leu Trp Met Lys Trp Arg Ile Asp Arg
115 120 125
Val Ile Ser Trp Ile Leu Leu Gly Cys Val Val Leu Ser Val Phe Ile
130 135 140
Ser Leu Pro Ala Thr Glu Asn Leu Asn Ala Asp Phe Arg Phe Cys Val
145 150 155 160
Lys Ala Lys Arg Lys Thr Asn Leu Thr Trp Ser Cys Arg Val Asn Lys
165 170 175
Thr Gln His Ala Ser Thr Lys Leu Phe Leu Asn Leu Ala Thr Leu Leu
180 185 190
Pro Phe Cys Val Cys Leu Met Ser Phe Phe Leu Leu Ile Leu Ser Leu
195 200 205
Arg Arg His Ile Arg Arg Met Gln Leu Ser Ala Thr Gly Cys Arg Asp
210 215 220
Pro Ser Thr Glu Ala His Val Arg Ala Leu Lys Ala Val Ile Ser Phe
225 230 235 240
Leu Leu Leu Phe Ile Ala Tyr Tyr Leu Ser Phe Leu Ile Ala Thr Ser
245 250 255
Ser Tyr Phe Met Pro Glu Thr Glu Leu Ala Val Ile Phe Gly Glu Ser
260 265 270
Ile Ala Leu Ile Tyr Pro Ser Ser His Ser Phe Ile Leu Ile Leu Gly
275 280 285
Asn Asn Lys Leu Arg His Ala Ser Leu Lys Val Ile Trp Lys Val Met
290 295 300
Ser Ile Leu Lys Gly Arg Lys Phe Gln Gln His Lys Gln Ile
305 310 315
<210> 11
<211> 930
<212> DNA
<213> 智人
<220>
<221> CDS
<222> (1)..(930)
<400> 11
atg ttc agt cct gca gat aac atc ttt ata atc cta ata act gga gaa 48
Met Phe Ser Pro Ala Asp Asn Ile Phe Ile Ile Leu Ile Thr Gly Glu
1 5 10 15
ttc ata cta gga ata ttg ggg aat gga tac att gca cta gtc aac tgg 96
Phe Ile Leu Gly Ile Leu Gly Asn Gly Tyr Ile Ala Leu Val Asn Trp
20 25 30
att gac tgg att aag aag aaa aag att tcc aca gtt gac tac atc ctt 144
Ile Asp Trp Ile Lys Lys Lys Lys Ile Ser Thr Val Asp Tyr Ile Leu
35 40 45
acc aat tta gtt atc gcc aga att tgt ttg atc agt gta atg gtt gta 192
Thr Asn Leu Val Ile Ala Arg Ile Cys Leu Ile Ser Val Met Val Val
50 55 60
aat ggc att gta ata gta ctg aac cca gat gtt tat aca aaa aat aaa 240
Asn Gly Ile Val Ile Val Leu Asn Pro Asp Val Tyr Thr Lys Asn Lys
65 70 75 80
caa cag ata gtc att ttt acc ttc tgg aca ttt gcc aac tac tta aat 288
Gln Gln Ile Val Ile Phe Thr Phe Trp Thr Phe Ala Asn Tyr Leu Asn
85 90 95
atg tgg att acc acc tgc ctt aat gtc ttc tat ttt ctg aag ata gcc 336
Met Trp Ile Thr Thr Cys Leu Asn Val Phe Tyr Phe Leu Lys Ile Ala
100 105 110
agt tcc tct cat cca ctt ttt ctc tgg ctg aag tgg aaa att gat atg 384
Ser Ser Ser His Pro Leu Phe Leu Trp Leu Lys Trp Lys Ile Asp Met
115 120 125
gtg gtg cac tgg atc ctg ctg gga tgc ttt gcc att tcc ttg ttg gtc 432
Val Val His Trp Ile Leu Leu Gly Cys Phe Ala Ile Ser Leu Leu Val
130 135 140
agc ctt ata gca gca ata gta ctg agt tgt gat tat agg ttt cat gca 480
Ser Leu Ile Ala Ala Ile Val Leu Ser Cys Asp Tyr Arg Phe His Ala
145 150 155 160
att gcc aaa cat aaa aga aac att act gaa atg ttc cat gtg agt aaa 528
Ile Ala Lys His Lys Arg Asn Ile Thr Glu Met Phe His Val Ser Lys
165 170 175
ata cca tac ttt gaa ccc ttg act ctc ttt aac ctg ttt gca att gtc 576
Ile Pro Tyr Phe Glu Pro Leu Thr Leu Phe Asn Leu Phe Ala Ile Val
180 185 190
cca ttt att gtg tca ctg ata tca ttt ttc ctt tta gta aga tct tta 624
Pro Phe Ile Val Ser Leu Ile Ser Phe Phe Leu Leu Val Arg Ser Leu
195 200 205
tgg aga cat acc aag caa ata aaa ctc tat gct acc ggc agt aga gac 672
Trp Arg His Thr Lys Gln Ile Lys Leu Tyr Ala Thr Gly Ser Arg Asp
210 215 220
ccc agc aca gaa gtt cat gtg aga gcc att aaa act atg act tca ttt 720
Pro Ser Thr Glu Val His Val Arg Ala Ile Lys Thr Met Thr Ser Phe
225 230 235 240
atc ttc ttt ttt ttc cta tac tat att tct tct att ttg atg acc ttt 768
Ile Phe Phe Phe Phe Leu Tyr Tyr Ile Ser Ser Ile Leu Met Thr Phe
245 250 255
agc tat ctt atg aca aaa tac aag tta gct gtg gag ttt gga gag att 816
Ser Tyr Leu Met Thr Lys Tyr Lys Leu Ala Val Glu Phe Gly Glu Ile
260 265 270
gca gca att ctc tac ccc ttg ggt cac tca ctt att tta att gtt tta 864
Ala Ala Ile Leu Tyr Pro Leu Gly His Ser Leu Ile Leu Ile Val Leu
275 280 285
aat aat aaa ctg agg cag aca ttt gtc aga atg ctg aca tgt aga aaa 912
Asn Asn Lys Leu Arg Gln Thr Phe Val Arg Met Leu Thr Cys Arg Lys
290 295 300
att gcc tgc atg ata tga 930
Ile Ala Cys Met Ile
305
<210> 12
<211> 309
<212> PRT
<213> 智人
<400> 12
Met Phe Ser Pro Ala Asp Asn Ile Phe Ile Ile Leu Ile Thr Gly Glu
1 5 10 15
Phe Ile Leu Gly Ile Leu Gly Asn Gly Tyr Ile Ala Leu Val Asn Trp
20 25 30
Ile Asp Trp Ile Lys Lys Lys Lys Ile Ser Thr Val Asp Tyr Ile Leu
35 40 45
Thr Asn Leu Val Ile Ala Arg Ile Cys Leu Ile Ser Val Met Val Val
50 55 60
Asn Gly Ile Val Ile Val Leu Asn Pro Asp Val Tyr Thr Lys Asn Lys
65 70 75 80
Gln Gln Ile Val Ile Phe Thr Phe Trp Thr Phe Ala Asn Tyr Leu Asn
85 90 95
Met Trp Ile Thr Thr Cys Leu Asn Val Phe Tyr Phe Leu Lys Ile Ala
100 105 110
Ser Ser Ser His Pro Leu Phe Leu Trp Leu Lys Trp Lys Ile Asp Met
115 120 125
Val Val His Trp Ile Leu Leu Gly Cys Phe Ala Ile Ser Leu Leu Val
130 135 140
Ser Leu Ile Ala Ala Ile Val Leu Ser Cys Asp Tyr Arg Phe His Ala
145 150 155 160
Ile Ala Lys His Lys Arg Asn Ile Thr Glu Met Phe His Val Ser Lys
165 170 175
Ile Pro Tyr Phe Glu Pro Leu Thr Leu Phe Asn Leu Phe Ala Ile Val
180 185 190
Pro Phe Ile Val Ser Leu Ile Ser Phe Phe Leu Leu Val Arg Ser Leu
195 200 205
Trp Arg His Thr Lys Gln Ile Lys Leu Tyr Ala Thr Gly Ser Arg Asp
210 215 220
Pro Ser Thr Glu Val His Val Arg Ala Ile Lys Thr Met Thr Ser Phe
225 230 235 240
Ile Phe Phe Phe Phe Leu Tyr Tyr Ile Ser Ser Ile Leu Met Thr Phe
245 250 255
Ser Tyr Leu Met Thr Lys Tyr Lys Leu Ala Val Glu Phe Gly Glu Ile
260 265 270
Ala Ala Ile Leu Tyr Pro Leu Gly His Ser Leu Ile Leu Ile Val Leu
275 280 285
Asn Asn Lys Leu Arg Gln Thr Phe Val Arg Met Leu Thr Cys Arg Lys
290 295 300
Ile Ala Cys Met Ile
305
<210> 13
<211> 939
<212> DNA
<213> 智人
<220>
<221> CDS
<222> (1)..(939)
<400> 13
atg cca agt gca ata gag gca ata tat att att tta att gct ggt gaa 48
Met Pro Ser Ala Ile Glu Ala Ile Tyr Ile Ile Leu Ile Ala Gly Glu
1 5 10 15
ttg acc ata ggg att tgg gga aat gga ttc att gta cta gtt aac tgc 96
Leu Thr Ile Gly Ile Trp Gly Asn Gly Phe Ile Val Leu Val Asn Cys
20 25 30
att gac tgg ctc aaa aga aga gat att tcc ttg att gac atc atc ctg 144
Ile Asp Trp Leu Lys Arg Arg Asp Ile Ser Leu Ile Asp Ile Ile Leu
35 40 45
atc agc ttg gcc atc tcc aga atc tgt ctg ctg tgt gta ata tca tta 192
Ile Ser Leu Ala Ile Ser Arg Ile Cys Leu Leu Cys Val Ile Ser Leu
50 55 60
gat ggc ttc ttt atg ctg ctc ttt cca ggt aca tat ggc aat agc gtg 240
Asp Gly Phe Phe Met Leu Leu Phe Pro Gly Thr Tyr Gly Asn Ser Val
65 70 75 80
cta gta agc att gtg aat gtt gtc tgg aca ttt gcc aat aat tca agt 288
Leu Val Ser Ile Val Asn Val Val Trp Thr Phe Ala Asn Asn Ser Ser
85 90 95
ctc tgg ttt act tct tgc ctc agt atc ttc tat tta ctc aag ata gcc 336
Leu Trp Phe Thr Ser Cys Leu Ser Ile Phe Tyr Leu Leu Lys Ile Ala
100 105 110
aat ata tcg cac cca ttt ttc ttc tgg ctg aag cta aag atc aac aag 384
Asn Ile Ser His Pro Phe Phe Phe Trp Leu Lys Leu Lys Ile Asn Lys
115 120 125
gtc atg ctt gcg att ctt ctg ggg tcc ttt ctt atc tct tta att att 432
Val Met Leu Ala Ile Leu Leu Gly Ser Phe Leu Ile Ser Leu Ile Ile
130 135 140
agt gtt cca aag aat gat gat atg tgg tat cac ctt ttc aaa gtc agt 480
Ser Val Pro Lys Asn Asp Asp Met Trp Tyr His Leu Phe Lys Val Ser
145 150 155 160
cat gaa gaa aac att act tgg aaa ttc aaa gtg agt aaa att cca ggt 528
His Glu Glu Asn Ile Thr Trp Lys Phe Lys Val Ser Lys Ile Pro Gly
165 170 175
act ttc aaa cag tta acc ctg aac ctg ggg gtg atg gtt ccc ttt atc 576
Thr Phe Lys Gln Leu Thr Leu Asn Leu Gly Val Met Val Pro Phe Ile
180 185 190
ctt tgc ctg atc tca ttt ttc ttg tta ctt ttc tcc cta gtt aga cac 624
Leu Cys Leu Ile Ser Phe Phe Leu Leu Leu Phe Ser Leu Val Arg His
195 200 205
acc aag cag att cga ctg cat gct aca ggg ttc aga gac ccc agt aca 672
Thr Lys Gln Ile Arg Leu His Ala Thr Gly Phe Arg Asp Pro Ser Thr
210 215 220
gag gcc cac atg agg gcc ata aag gca gtg atc atc ttt ctg ctc ctc 720
Glu Ala His Met Arg Ala Ile Lys Ala Val Ile Ile Phe Leu Leu Leu
225 230 235 240
ctc atc gtg tac tac cca gtc ttt ctt gtt atg acc tct agc gct ctg 768
Leu Ile Val Tyr Tyr Pro Val Phe Leu Val Met Thr Ser Ser Ala Leu
245 250 255
att cct cag gga aaa tta gtg ttg atg att ggt gac ata gta act gtc 816
Ile Pro Gln Gly Lys Leu Val Leu Met Ile Gly Asp Ile Val Thr Val
260 265 270
att ttc cca tca agc cat tca ttc att cta att atg gga aat agc aag 864
Ile Phe Pro Ser Ser His Ser Phe Ile Leu Ile Met Gly Asn Ser Lys
275 280 285
ttg agg gaa gct ttt ctg aag atg tta aga ttt gtg aag tgt ttc ctt 912
Leu Arg Glu Ala Phe Leu Lys Met Leu Arg Phe Val Lys Cys Phe Leu
290 295 300
aga aga aga aag cct ttt gtt cca tag 939
Arg Arg Arg Lys Pro Phe Val Pro
305 310
<210> 14
<211> 312
<212> PRT
<213> 智人
<400> 14
Met Pro Ser Ala Ile Glu Ala Ile Tyr Ile Ile Leu Ile Ala Gly Glu
1 5 10 15
Leu Thr Ile Gly Ile Trp Gly Asn Gly Phe Ile Val Leu Val Asn Cys
20 25 30
Ile Asp Trp Leu Lys Arg Arg Asp Ile Ser Leu Ile Asp Ile Ile Leu
35 40 45
Ile Ser Leu Ala Ile Ser Arg Ile Cys Leu Leu Cys Val Ile Ser Leu
50 55 60
Asp Gly Phe Phe Met Leu Leu Phe Pro Gly Thr Tyr Gly Asn Ser Val
65 70 75 80
Leu Val Ser Ile Val Asn Val Val Trp Thr Phe Ala Asn Asn Ser Ser
85 90 95
Leu Trp Phe Thr Ser Cys Leu Ser Ile Phe Tyr Leu Leu Lys Ile Ala
100 105 110
Asn Ile Ser His Pro Phe Phe Phe Trp Leu Lys Leu Lys Ile Asn Lys
115 120 125
Val Met Leu Ala Ile Leu Leu Gly Ser Phe Leu Ile Ser Leu Ile Ile
130 135 140
Ser Val Pro Lys Asn Asp Asp Met Trp Tyr His Leu Phe Lys Val Ser
145 150 155 160
His Glu Glu Asn Ile Thr Trp Lys Phe Lys Val Ser Lys Ile Pro Gly
165 170 175
Thr Phe Lys Gln Leu Thr Leu Asn Leu Gly Val Met Val Pro Phe Ile
180 185 190
Leu Cys Leu Ile Ser Phe Phe Leu Leu Leu Phe Ser Leu Val Arg His
195 200 205
Thr Lys Gln Ile Arg Leu His Ala Thr Gly Phe Arg Asp Pro Ser Thr
210 215 220
Glu Ala His Met Arg Ala Ile Lys Ala Val Ile Ile Phe Leu Leu Leu
225 230 235 240
Leu Ile Val Tyr Tyr Pro Val Phe Leu Val Met Thr Ser Ser Ala Leu
245 250 255
Ile Pro Gln Gly Lys Leu Val Leu Met Ile Gly Asp Ile Val Thr Val
260 265 270
Ile Phe Pro Ser Ser His Ser Phe Ile Leu Ile Met Gly Asn Ser Lys
275 280 285
Leu Arg Glu Ala Phe Leu Lys Met Leu Arg Phe Val Lys Cys Phe Leu
290 295 300
Arg Arg Arg Lys Pro Phe Val Pro
305 310
<210> 15
<211> 924
<212> DNA
<213> 智人
<220>
<221> CDS
<222> (1)..(924)
<400> 15
atg cta cgt gta gtg gaa ggc atc ttc att ttt gtt gta gtt agt gag 48
Met Leu Arg Val Val Glu Gly Ile Phe Ile Phe Val Val Val Ser Glu
1 5 10 15
tca gtg ttt ggg gtt ttg ggg aat gga ttt att gga ctt gta aac tgc 96
Ser Val Phe Gly Val Leu Gly Asn Gly Phe Ile Gly Leu Val Asn Cys
20 25 30
att gac tgt gcc aag aat aag tta tct acg att ggc ttt att ctc acc 144
Ile Asp Cys Ala Lys Asn Lys Leu Ser Thr Ile Gly Phe Ile Leu Thr
35 40 45
ggc tta gct att tca aga att ttt ctg ata tgg ata ata att aca gat 192
Gly Leu Ala Ile Ser Arg Ile Phe Leu Ile Trp Ile Ile Ile Thr Asp
50 55 60
gga ttt ata cag ata ttc tct cca aat ata tat gcc tcc ggt aac cta 240
Gly Phe Ile Gln Ile Phe Ser Pro Asn Ile Tyr Ala Ser Gly Asn Leu
65 70 75 80
att gaa tat att agt tac ttt tgg gta att ggt aat caa tca agt atg 288
Ile Glu Tyr Ile Ser Tyr Phe Trp Val Ile Gly Asn Gln Ser Ser Met
85 90 95
tgg ttt gcc acc agc ctc agc atc ttc tat ttc ctg aag ata gca aat 336
Trp Phe Ala Thr Ser Leu Ser Ile Phe Tyr Phe Leu Lys Ile Ala Asn
100 105 110
ttt tcc aac tac ata ttt ctc tgg ttg aag agc aga aca aat atg gtt 384
Phe Ser Asn Tyr Ile Phe Leu Trp Leu Lys Ser Arg Thr Asn Met Val
115 120 125
ctt ccc ttc atg ata gta ttc tta ctt att tca tcg tta ctt aat ttt 432
Leu Pro Phe Met Ile Val Phe Leu Leu Ile Ser Ser Leu Leu Asn Phe
130 135 140
gca tac att gcg aag att ctt aat gat tat aaa acg aag aat gac aca 480
Ala Tyr Ile Ala Lys Ile Leu Asn Asp Tyr Lys Thr Lys Asn Asp Thr
145 150 155 160
gtc tgg gat ctc aac atg tat aaa agt gaa tac ttt att aaa cag att 528
Val Trp Asp Leu Asn Met Tyr Lys Ser Glu Tyr Phe Ile Lys Gln Ile
165 170 175
ttg cta aat ctg gga gtc att ttc ttc ttt aca cta tcc cta att aca 576
Leu Leu Asn Leu Gly Val Ile Phe Phe Phe Thr Leu Ser Leu Ile Thr
180 185 190
tgt att ttt tta atc att tcc ctt tgg aga cac aac agg cag atg caa 624
Cys Ile Phe Leu Ile Ile Ser Leu Trp Arg His Asn Arg Gln Met Gln
195 200 205
tcg aat gtg aca gga ttg aga gac tcc aac aca gaa gct cat gtg aag 672
Ser Asn Val Thr Gly Leu Arg Asp Ser Asn Thr Glu Ala His Val Lys
210 215 220
gca atg aaa gtt ttg ata tct ttc atc atc ctc ttt atc ttg tat ttt 720
Ala Met Lys Val Leu Ile Ser Phe Ile Ile Leu Phe Ile Leu Tyr Phe
225 230 235 240
ata ggc atg gcc ata gaa ata tca tgt ttt act gtg cga gaa aac aaa 768
Ile Gly Met Ala Ile Glu Ile Ser Cys Phe Thr Val Arg Glu Asn Lys
245 250 255
ctg ctg ctt atg ttt gga atg aca acc aca gcc atc tat ccc tgg ggt 816
Leu Leu Leu Met Phe Gly Met Thr Thr Thr Ala Ile Tyr Pro Trp Gly
260 265 270
cac tca ttt atc tta att cta gga aac agc aag cta aag caa gcc tct 864
His Ser Phe Ile Leu Ile Leu Gly Asn Ser Lys Leu Lys Gln Ala Ser
275 280 285
ttg agg gta ctg cag caa ttg aag tgc tgt gag aaa agg aaa aat ctc 912
Leu Arg Val Leu Gln Gln Leu Lys Cys Cys Glu Lys Arg Lys Asn Leu
290 295 300
aga gtc aca tag 924
Arg Val Thr
305
<210> 16
<211> 307
<212> PRT
<213> 智人
<400> 16
Met Leu Arg Val Val Glu Gly Ile Phe Ile Phe Val Val Val Ser Glu
1 5 10 15
Ser Val Phe Gly Val Leu Gly Asn Gly Phe Ile Gly Leu Val Asn Cys
20 25 30
Ile Asp Cys Ala Lys Asn Lys Leu Ser Thr Ile Gly Phe Ile Leu Thr
35 40 45
Gly Leu Ala Ile Ser Arg Ile Phe Leu Ile Trp Ile Ile Ile Thr Asp
50 55 60
Gly Phe Ile Gln Ile Phe Ser Pro Asn Ile Tyr Ala Ser Gly Asn Leu
65 70 75 80
Ile Glu Tyr Ile Ser Tyr Phe Trp Val Ile Gly Asn Gln Ser Ser Met
85 90 95
Trp Phe Ala Thr Ser Leu Ser Ile Phe Tyr Phe Leu Lys Ile Ala Asn
100 105 110
Phe Ser Asn Tyr Ile Phe Leu Trp Leu Lys Ser Arg Thr Asn Met Val
115 120 125
Leu Pro Phe Met Ile Val Phe Leu Leu Ile Ser Ser Leu Leu Asn Phe
130 135 140
Ala Tyr Ile Ala Lys Ile Leu Asn Asp Tyr Lys Thr Lys Asn Asp Thr
145 150 155 160
Val Trp Asp Leu Asn Met Tyr Lys Ser Glu Tyr Phe Ile Lys Gln Ile
165 170 175
Leu Leu Asn Leu Gly Val Ile Phe Phe Phe Thr Leu Ser Leu Ile Thr
180 185 190
Cys Ile Phe Leu Ile Ile Ser Leu Trp Arg His Asn Arg Gln Met Gln
195 200 205
Ser Asn Val Thr Gly Leu Arg Asp Ser Asn Thr Glu Ala His Val Lys
210 215 220
Ala Met Lys Val Leu Ile Ser Phe Ile Ile Leu Phe Ile Leu Tyr Phe
225 230 235 240
Ile Gly Met Ala Ile Glu Ile Ser Cys Phe Thr Val Arg Glu Asn Lys
245 250 255
Leu Leu Leu Met Phe Gly Met Thr Thr Thr Ala Ile Tyr Pro Trp Gly
260 265 270
His Ser Phe Ile Leu Ile Leu Gly Asn Ser Lys Leu Lys Gln Ala Ser
275 280 285
Leu Arg Val Leu Gln Gln Leu Lys Cys Cys Glu Lys Arg Lys Asn Leu
290 295 300
Arg Val Thr
305
<210> 17
<211> 912
<212> DNA
<213> 智人
<220>
<221> CDS
<222> (1)..(912)
<400> 17
atg gaa agt gcc ctg ccg agt atc ttc act ctt gta ata att gca gaa 48
Met Glu Ser Ala Leu Pro Ser Ile Phe Thr Leu Val Ile Ile Ala Glu
1 5 10 15
ttc ata att ggg aat ttg agc aat gga ttt ata gta ctg atc aac tgc 96
Phe Ile Ile Gly Asn Leu Ser Asn Gly Phe Ile Val Leu Ile Asn Cys
20 25 30
att gac tgg gtc agt aaa aga gag ctg tcc tca gtc gat aaa ctc ctc 144
Ile Asp Trp Val Ser Lys Arg Glu Leu Ser Ser Val Asp Lys Leu Leu
35 40 45
att atc ttg gca atc tcc aga att ggg ctg atc tgg gaa ata tta gta 192
Ile Ile Leu Ala Ile Ser Arg Ile Gly Leu Ile Trp Glu Ile Leu Val
50 55 60
agt tgg ttt tta gct ctg cat tat cta gcc ata ttt gtg tct gga aca 240
Ser Trp Phe Leu Ala Leu His Tyr Leu Ala Ile Phe Val Ser Gly Thr
65 70 75 80
gga tta aga att atg att ttt agc tgg ata gtt tct aat cac ttc aat 288
Gly Leu Arg Ile Met Ile Phe Ser Trp Ile Val Ser Asn His Phe Asn
85 90 95
ctc tgg ctt gct aca atc ttc agc atc ttt tat ttg ctc aaa ata gcg 336
Leu Trp Leu Ala Thr Ile Phe Ser Ile Phe Tyr Leu Leu Lys Ile Ala
100 105 110
agt ttc tct agc cct gct ttt ctc tat ttg aag tgg aga gta aac aaa 384
Ser Phe Ser Ser Pro Ala Phe Leu Tyr Leu Lys Trp Arg Val Asn Lys
115 120 125
gtg att ctg atg ata ctg cta gga acc ttg gtc ttc tta ttt tta aat 432
Val Ile Leu Met Ile Leu Leu Gly Thr Leu Val Phe Leu Phe Leu Asn
130 135 140
ctg ata caa ata aac atg cat ata aaa gac tgg ctg gac cga tat gaa 480
Leu Ile Gln Ile Asn Met His Ile Lys Asp Trp Leu Asp Arg Tyr Glu
145 150 155 160
aga aac aca act tgg aat ttc agt atg agt gac ttt gaa aca ttt tca 528
Arg Asn Thr Thr Trp Asn Phe Ser Met Ser Asp Phe Glu Thr Phe Ser
165 170 175
gtg tcg gtc aaa ttc act atg act atg ttc agt cta aca cca ttt act 576
Val Ser Val Lys Phe Thr Met Thr Met Phe Ser Leu Thr Pro Phe Thr
180 185 190
gtg gcc ttc atc tct ttt ctc ctg tta att ttc tcc ctg cag aaa cat 624
Val Ala Phe Ile Ser Phe Leu Leu Leu Ile Phe Ser Leu Gln Lys His
195 200 205
ctc cag aaa atg caa ctc aat tac aaa gga cac aga gac ccc agg acc 672
Leu Gln Lys Met Gln Leu Asn Tyr Lys Gly His Arg Asp Pro Arg Thr
210 215 220
aag gtc cat aca aat gcc ttg aaa att gtg atc tca ttc ctt tta ttc 720
Lys Val His Thr Asn Ala Leu Lys Ile Val Ile Ser Phe Leu Leu Phe
225 230 235 240
tat gct agt ttc ttt cta tgt gtt ctc ata tca tgg att tct gag ctg 768
Tyr Ala Ser Phe Phe Leu Cys Val Leu Ile Ser Trp Ile Ser Glu Leu
245 250 255
tat cag aac aca gtg atc tac atg ctt tgt gag acg att gga gtc ttc 816
Tyr Gln Asn Thr Val Ile Tyr Met Leu Cys Glu Thr Ile Gly Val Phe
260 265 270
tct cct tca agc cac tcc ttt ctt ctg att cta gga aac gct aag tta 864
Ser Pro Ser Ser His Ser Phe Leu Leu Ile Leu Gly Asn Ala Lys Leu
275 280 285
aga cag gcc ttt ctt ttg gtg gca gct aag gta tgg gct aaa cga tga 912
Arg Gln Ala Phe Leu Leu Val Ala Ala Lys Val Trp Ala Lys Arg
290 295 300
<210> 18
<211> 303
<212> PRT
<213> 智人
<400> 18
Met Glu Ser Ala Leu Pro Ser Ile Phe Thr Leu Val Ile Ile Ala Glu
1 5 10 15
Phe Ile Ile Gly Asn Leu Ser Asn Gly Phe Ile Val Leu Ile Asn Cys
20 25 30
Ile Asp Trp Val Ser Lys Arg Glu Leu Ser Ser Val Asp Lys Leu Leu
35 40 45
Ile Ile Leu Ala Ile Ser Arg Ile Gly Leu Ile Trp Glu Ile Leu Val
50 55 60
Ser Trp Phe Leu Ala Leu His Tyr Leu Ala Ile Phe Val Ser Gly Thr
65 70 75 80
Gly Leu Arg Ile Met Ile Phe Ser Trp Ile Val Ser Asn His Phe Asn
85 90 95
Leu Trp Leu Ala Thr Ile Phe Ser Ile Phe Tyr Leu Leu Lys Ile Ala
100 105 110
Ser Phe Ser Ser Pro Ala Phe Leu Tyr Leu Lys Trp Arg Val Asn Lys
115 120 125
Val Ile Leu Met Ile Leu Leu Gly Thr Leu Val Phe Leu Phe Leu Asn
130 135 140
Leu Ile Gln Ile Asn Met His Ile Lys Asp Trp Leu Asp Arg Tyr Glu
145 150 155 160
Arg Asn Thr Thr Trp Asn Phe Ser Met Ser Asp Phe Glu Thr Phe Ser
165 170 175
Val Ser Val Lys Phe Thr Met Thr Met Phe Ser Leu Thr Pro Phe Thr
180 185 190
Val Ala Phe Ile Ser Phe Leu Leu Leu Ile Phe Ser Leu Gln Lys His
195 200 205
Leu Gln Lys Met Gln Leu Asn Tyr Lys Gly His Arg Asp Pro Arg Thr
210 215 220
Lys Val His Thr Asn Ala Leu Lys Ile Val Ile Ser Phe Leu Leu Phe
225 230 235 240
Tyr Ala Ser Phe Phe Leu Cys Val Leu Ile Ser Trp Ile Ser Glu Leu
245 250 255
Tyr Gln Asn Thr Val Ile Tyr Met Leu Cys Glu Thr Ile Gly Val Phe
260 265 270
Ser Pro Ser Ser His Ser Phe Leu Leu Ile Leu Gly Asn Ala Lys Leu
275 280 285
Arg Gln Ala Phe Leu Leu Val Ala Ala Lys Val Trp Ala Lys Arg
290 295 300
<210> 19
<211> 954
<212> DNA
<213> 智人
<220>
<221> CDS
<222> (1)..(954)
<400> 19
atg ggt ggt gtc ata aag agc ata ttt aca ttc gtt tta att gtg gaa 48
Met Gly Gly Val Ile Lys Ser Ile Phe Thr Phe Val Leu Ile Val Glu
1 5 10 15
ttt ata att gga aat tta gga aat agt ttc ata gca ctg gtg aac tgt 96
Phe Ile Ile Gly Asn Leu Gly Asn Ser Phe Ile Ala Leu Val Asn Cys
20 25 30
att gac tgg gtc aag gga aga aag atc tct tcg gtt gat cgg atc ctc 144
Ile Asp Trp Val Lys Gly Arg Lys Ile Ser Ser Val Asp Arg Ile Leu
35 40 45
act gct ttg gca atc tct cga att agc ctg gtt tgg tta ata ttc gga 192
Thr Ala Leu Ala Ile Ser Arg Ile Ser Leu Val Trp Leu Ile Phe Gly
50 55 60
agc tgg tgt gtg tct gtg ttt ttc cca gct tta ttt gcc act gaa aaa 240
Ser Trp Cys Val Ser Val Phe Phe Pro Ala Leu Phe Ala Thr Glu Lys
65 70 75 80
atg ttc aga atg ctt act aat atc tgg aca gtg atc aat cat ttt agt 288
Met Phe Arg Met Leu Thr Asn Ile Trp Thr Val Ile Asn His Phe Ser
85 90 95
gtc tgg tta gct aca ggc ctc ggt act ttt tat ttt ctc aag ata gcc 336
Val Trp Leu Ala Thr Gly Leu Gly Thr Phe Tyr Phe Leu Lys Ile Ala
100 105 110
aat ttt tct aac tct att ttt ctc tac cta aag tgg agg gtt aaa aag 384
Asn Phe Ser Asn Ser Ile Phe Leu Tyr Leu Lys Trp Arg Val Lys Lys
115 120 125
gtg gtt ttg gtg ctg ctt ctt gtg act tcg gtc ttc ttg ttt tta aat 432
Val Val Leu Val Leu Leu Leu Val Thr Ser Val Phe Leu Phe Leu Asn
130 135 140
att gca ctg ata aac atc cat ata aat gcc agt atc aat gga tac aga 480
Ile Ala Leu Ile Asn Ile His Ile Asn Ala Ser Ile Asn Gly Tyr Arg
145 150 155 160
aga aac aag act tgc agt tct gat tca agt aac ttt aca cga ttt tcc 528
Arg Asn Lys Thr Cys Ser Ser Asp Ser Ser Asn Phe Thr Arg Phe Ser
165 170 175
agt ctt att gta tta acc agc act gtg ttc att ttc ata ccc ttt act 576
Ser Leu Ile Val Leu Thr Ser Thr Val Phe Ile Phe Ile Pro Phe Thr
180 185 190
ttg tcc ctg gca atg ttt ctt ctc ctc atc ttc tcc atg tgg aaa cat 624
Leu Ser Leu Ala Met Phe Leu Leu Leu Ile Phe Ser Met Trp Lys His
195 200 205
cgc aag aag atg cag cac act gtc aaa ata tcc gga gac gcc agc acc 672
Arg Lys Lys Met Gln His Thr Val Lys Ile Ser Gly Asp Ala Ser Thr
210 215 220
aaa gcc cac aga gga gtt aaa agt gtg atc act ttc ttc cta ctc tat 720
Lys Ala His Arg Gly Val Lys Ser Val Ile Thr Phe Phe Leu Leu Tyr
225 230 235 240
gcc att ttc tct ctg tct ttt ttc ata tca gtt tgg acc tct gaa agg 768
Ala Ile Phe Ser Leu Ser Phe Phe Ile Ser Val Trp Thr Ser Glu Arg
245 250 255
ttg gag gaa aat cta att att ctt tcc cag gtg atg gga atg gct tat 816
Leu Glu Glu Asn Leu Ile Ile Leu Ser Gln Val Met Gly Met Ala Tyr
260 265 270
cct tca tgt cac tca tgt gtt ctg att ctt gga aac aag aag ctg aga 864
Pro Ser Cys His Ser Cys Val Leu Ile Leu Gly Asn Lys Lys Leu Arg
275 280 285
cag gcc tct ctg tca gtg cta ctg tgg ctg agg tac atg ttc aaa gat 912
Gln Ala Ser Leu Ser Val Leu Leu Trp Leu Arg Tyr Met Phe Lys Asp
290 295 300
ggg gag ccc tca ggt cac aaa gaa ttt aga gaa tca tct tga 954
Gly Glu Pro Ser Gly His Lys Glu Phe Arg Glu Ser Ser
305 310 315
<210> 20
<211> 317
<212> PRT
<213> 智人
<400> 20
Met Gly Gly Val Ile Lys Ser Ile Phe Thr Phe Val Leu Ile Val Glu
1 5 10 15
Phe Ile Ile Gly Asn Leu Gly Asn Ser Phe Ile Ala Leu Val Asn Cys
20 25 30
Ile Asp Trp Val Lys Gly Arg Lys Ile Ser Ser Val Asp Arg Ile Leu
35 40 45
Thr Ala Leu Ala Ile Ser Arg Ile Ser Leu Val Trp Leu Ile Phe Gly
50 55 60
Ser Trp Cys Val Ser Val Phe Phe Pro Ala Leu Phe Ala Thr Glu Lys
65 70 75 80
Met Phe Arg Met Leu Thr Asn Ile Trp Thr Val Ile Asn His Phe Ser
85 90 95
Val Trp Leu Ala Thr Gly Leu Gly Thr Phe Tyr Phe Leu Lys Ile Ala
100 105 110
Asn Phe Ser Asn Ser Ile Phe Leu Tyr Leu Lys Trp Arg Val Lys Lys
115 120 125
Val Val Leu Val Leu Leu Leu Val Thr Ser Val Phe Leu Phe Leu Asn
130 135 140
Ile Ala Leu Ile Asn Ile His Ile Asn Ala Ser Ile Asn Gly Tyr Arg
145 150 155 160
Arg Asn Lys Thr Cys Ser Ser Asp Ser Ser Asn Phe Thr Arg Phe Ser
165 170 175
Ser Leu Ile Val Leu Thr Ser Thr Val Phe Ile Phe Ile Pro Phe Thr
180 185 190
Leu Ser Leu Ala Met Phe Leu Leu Leu Ile Phe Ser Met Trp Lys His
195 200 205
Arg Lys Lys Met Gln His Thr Val Lys Ile Ser Gly Asp Ala Ser Thr
210 215 220
Lys Ala His Arg Gly Val Lys Ser Val Ile Thr Phe Phe Leu Leu Tyr
225 230 235 240
Ala Ile Phe Ser Leu Ser Phe Phe Ile Ser Val Trp Thr Ser Glu Arg
245 250 255
Leu Glu Glu Asn Leu Ile Ile Leu Ser Gln Val Met Gly Met Ala Tyr
260 265 270
Pro Ser Cys His Ser Cys Val Leu Ile Leu Gly Asn Lys Lys Leu Arg
275 280 285
Gln Ala Ser Leu Ser Val Leu Leu Trp Leu Arg Tyr Met Phe Lys Asp
290 295 300
Gly Glu Pro Ser Gly His Lys Glu Phe Arg Glu Ser Ser
305 310 315
<210> 21
<211> 876
<212> DNA
<213> 智人
<220>
<221> CDS
<222> (1)..(876)
<400> 21
atg ata ccc atc caa ctc act gtc ttc ttc atg atc atc tat gtg ctt 48
Met Ile Pro Ile Gln Leu Thr Val Phe Phe Met Ile Ile Tyr Val Leu
1 5 10 15
gag tcc ttg aca att att gtg cag agc agc cta att gtt gca gtg ctg 96
Glu Ser Leu Thr Ile Ile Val Gln Ser Ser Leu Ile Val Ala Val Leu
20 25 30
ggc aga gaa tgg ctg caa gtc aga agg ctg atg cct gtg gac atg att 144
Gly Arg Glu Trp Leu Gln Val Arg Arg Leu Met Pro Val Asp Met Ile
35 40 45
ctc atc agc ctg ggc atc tct cgc ttc tgt cta cag tgg gca tca atg 192
Leu Ile Ser Leu Gly Ile Ser Arg Phe Cys Leu Gln Trp Ala Ser Met
50 55 60
ctg aac aat ttt tgc tcc tat ttt aat ttg aat tat gta ctt tgc aac 240
Leu Asn Asn Phe Cys Ser Tyr Phe Asn Leu Asn Tyr Val Leu Cys Asn
65 70 75 80
tta aca atc acc tgg gaa ttt ttt aat atc ctt aca ttc tgg tta aac 288
Leu Thr Ile Thr Trp Glu Phe Phe Asn Ile Leu Thr Phe Trp Leu Asn
85 90 95
agc ttg ctt acc gtg ttc tac tgc atc aag gtc tct tct ttc acc cat 336
Ser Leu Leu Thr Val Phe Tyr Cys Ile Lys Val Ser Ser Phe Thr His
100 105 110
cac atc ttt ctc tgg ctg agg tgg aga att ttg agg ttg ttt ccc tgg 384
His Ile Phe Leu Trp Leu Arg Trp Arg Ile Leu Arg Leu Phe Pro Trp
115 120 125
ata tta ctg ggt tct ctg atg att act tgt gta aca atc atc cct tca 432
Ile Leu Leu Gly Ser Leu Met Ile Thr Cys Val Thr Ile Ile Pro Ser
130 135 140
gct att ggg aat tac att caa att cag tta ctc acc atg gag cat cta 480
Ala Ile Gly Asn Tyr Ile Gln Ile Gln Leu Leu Thr Met Glu His Leu
145 150 155 160
cca aga aac agc act gta act gac aaa ctt gaa aat ttt cat cag tat 528
Pro Arg Asn Ser Thr Val Thr Asp Lys Leu Glu Asn Phe His Gln Tyr
165 170 175
cag ttc cag gct cat aca gtt gca ttg gtt att cct ttc atc ctg ttc 576
Gln Phe Gln Ala His Thr Val Ala Leu Val Ile Pro Phe Ile Leu Phe
180 185 190
ctg gcc tcc acc atc ttt ctc atg gca tca ctg acc aag cag ata caa 624
Leu Ala Ser Thr Ile Phe Leu Met Ala Ser Leu Thr Lys Gln Ile Gln
195 200 205
cat cat agc act ggt cac tgc aat cca agc atg aaa gcg cgc ttc act 672
His His Ser Thr Gly His Cys Asn Pro Ser Met Lys Ala Arg Phe Thr
210 215 220
gcc ctg agg tcc ctt gcc gtc tta ttt att gtg ttt acc tct tac ttt 720
Ala Leu Arg Ser Leu Ala Val Leu Phe Ile Val Phe Thr Ser Tyr Phe
225 230 235 240
cta acc ata ctc atc acc att ata ggt act cta ttt gat aag aga tgt 768
Leu Thr Ile Leu Ile Thr Ile Ile Gly Thr Leu Phe Asp Lys Arg Cys
245 250 255
tgg tta tgg gtc tgg gaa gct ttt gtc tat gct ttc atc tta atg cat 816
Trp Leu Trp Val Trp Glu Ala Phe Val Tyr Ala Phe Ile Leu Met His
260 265 270
tcc act tca ctg atg ctg agc agc cct acg ttg aaa agg att cta aag 864
Ser Thr Ser Leu Met Leu Ser Ser Pro Thr Leu Lys Arg Ile Leu Lys
275 280 285
gga aag tgc tag 876
Gly Lys Cys
290
<210> 22
<211> 291
<212> PRT
<213> 智人
<400> 22
Met Ile Pro Ile Gln Leu Thr Val Phe Phe Met Ile Ile Tyr Val Leu
1 5 10 15
Glu Ser Leu Thr Ile Ile Val Gln Ser Ser Leu Ile Val Ala Val Leu
20 25 30
Gly Arg Glu Trp Leu Gln Val Arg Arg Leu Met Pro Val Asp Met Ile
35 40 45
Leu Ile Ser Leu Gly Ile Ser Arg Phe Cys Leu Gln Trp Ala Ser Met
50 55 60
Leu Asn Asn Phe Cys Ser Tyr Phe Asn Leu Asn Tyr Val Leu Cys Asn
65 70 75 80
Leu Thr Ile Thr Trp Glu Phe Phe Asn Ile Leu Thr Phe Trp Leu Asn
85 90 95
Ser Leu Leu Thr Val Phe Tyr Cys Ile Lys Val Ser Ser Phe Thr His
100 105 110
His Ile Phe Leu Trp Leu Arg Trp Arg Ile Leu Arg Leu Phe Pro Trp
115 120 125
Ile Leu Leu Gly Ser Leu Met Ile Thr Cys Val Thr Ile Ile Pro Ser
130 135 140
Ala Ile Gly Asn Tyr Ile Gln Ile Gln Leu Leu Thr Met Glu His Leu
145 150 155 160
Pro Arg Asn Ser Thr Val Thr Asp Lys Leu Glu Asn Phe His Gln Tyr
165 170 175
Gln Phe Gln Ala His Thr Val Ala Leu Val Ile Pro Phe Ile Leu Phe
180 185 190
Leu Ala Ser Thr Ile Phe Leu Met Ala Ser Leu Thr Lys Gln Ile Gln
195 200 205
His His Ser Thr Gly His Cys Asn Pro Ser Met Lys Ala Arg Phe Thr
210 215 220
Ala Leu Arg Ser Leu Ala Val Leu Phe Ile Val Phe Thr Ser Tyr Phe
225 230 235 240
Leu Thr Ile Leu Ile Thr Ile Ile Gly Thr Leu Phe Asp Lys Arg Cys
245 250 255
Trp Leu Trp Val Trp Glu Ala Phe Val Tyr Ala Phe Ile Leu Met His
260 265 270
Ser Thr Ser Leu Met Leu Ser Ser Pro Thr Leu Lys Arg Ile Leu Lys
275 280 285
Gly Lys Cys
290
<210> 23
<211> 1002
<212> DNA
<213> 智人
<220>
<221> CDS
<222> (1)..(1002)
<400> 23
atg ttg act cta act cgc atc cgc act gtg tcc tat gaa gtc agg agt 48
Met Leu Thr Leu Thr Arg Ile Arg Thr Val Ser Tyr Glu Val Arg Ser
1 5 10 15
aca ttt ctg ttc att tca gtc ctg gag ttt gca gtg ggg ttt ctg acc 96
Thr Phe Leu Phe Ile Ser Val Leu Glu Phe Ala Val Gly Phe Leu Thr
20 25 30
aat gcc ttc gtt ttc ttg gtg aat ttt tgg gat gta gtg aag agg cag 144
Asn Ala Phe Val Phe Leu Val Asn Phe Trp Asp Val Val Lys Arg Gln
35 40 45
cca ctg agc aac agt gat tgt gtg ctg ctg tgt ctc agc atc agc cgg 192
Pro Leu Ser Asn Ser Asp Cys Val Leu Leu Cys Leu Ser Ile Ser Arg
50 55 60
ctt ttc ctg cat gga ctg ctg ttc ctg agt gct atc cag ctt acc cac 240
Leu Phe Leu His Gly Leu Leu Phe Leu Ser Ala Ile Gln Leu Thr His
65 70 75 80
ttc cag aag ttg agt gaa cca ctg aac cac agc tac caa gcc atc atc 288
Phe Gln Lys Leu Ser Glu Pro Leu Asn His Ser Tyr Gln Ala Ile Ile
85 90 95
atg cta tgg atg att gca aac caa gcc aac ctc tgg ctt gct gcc tgc 336
Met Leu Trp Met Ile Ala Asn Gln Ala Asn Leu Trp Leu Ala Ala Cys
100 105 110
ctc agc ctg ctt tac tgc tcc aag ctc atc cgt ttc tct cac acc ttc 384
Leu Ser Leu Leu Tyr Cys Ser Lys Leu Ile Arg Phe Ser His Thr Phe
115 120 125
ctg atc tgc ttg gca agc tgg gtc tcc agg aag atc tcc cag atg ctc 432
Leu Ile Cys Leu Ala Ser Trp Val Ser Arg Lys Ile Ser Gln Met Leu
130 135 140
ctg ggt att att ctt tgc tcc tgc atc tgc act gtc ctc tgt gtt tgg 480
Leu Gly Ile Ile Leu Cys Ser Cys Ile Cys Thr Val Leu Cys Val Trp
145 150 155 160
tgc ttt ttt agc aga cct cac ttc aca gtc aca act gtg cta ttc atg 528
Cys Phe Phe Ser Arg Pro His Phe Thr Val Thr Thr Val Leu Phe Met
165 170 175
aat aac aat aca agg ctc aac tgg cag att aaa gat ctc aat tta ttt 576
Asn Asn Asn Thr Arg Leu Asn Trp Gln Ile Lys Asp Leu Asn Leu Phe
180 185 190
tat tcc ttt ctc ttc tgc tat ctg tgg tct gtg cct cct ttc cta ttg 624
Tyr Ser Phe Leu Phe Cys Tyr Leu Trp Ser Val Pro Pro Phe Leu Leu
195 200 205
ttt ctg gtt tct tct ggg atg ctg act gtc tcc ctg gga agg cac atg 672
Phe Leu Val Ser Ser Gly Met Leu Thr Val Ser Leu Gly Arg His Met
210 215 220
agg aca atg aag gtc tat acc aga aac tct cgt gac ccc agc ctg gag 720
Arg Thr Met Lys Val Tyr Thr Arg Asn Ser Arg Asp Pro Ser Leu Glu
225 230 235 240
gcc cac att aaa gcc ctc aag tct ctt gtc tcc ttt ttc tgc ttc ttt 768
Ala His Ile Lys Ala Leu Lys Ser Leu Val Ser Phe Phe Cys Phe Phe
245 250 255
gtg ata tca tcc tgt gct gcc ttc atc tct gtg ccc cta ctg att ctg 816
Val Ile Ser Ser Cys Ala Ala Phe Ile Ser Val Pro Leu Leu Ile Leu
260 265 270
tgg cgc gac aaa ata ggg gtg atg gtt tgt gtt ggg ata atg gca gct 864
Trp Arg Asp Lys Ile Gly Val Met Val Cys Val Gly Ile Met Ala Ala
275 280 285
tgt ccc tct ggg cat gca gcc gtc ctg atc tca ggc aat gcc aag ttg 912
Cys Pro Ser Gly His Ala Ala Val Leu Ile Ser Gly Asn Ala Lys Leu
290 295 300
agg aga gct gtg atg acc att ctg ctc tgg gct cag agc agc ctg aag 960
Arg Arg Ala Val Met Thr Ile Leu Leu Trp Ala Gln Ser Ser Leu Lys
305 310 315 320
gta aga gcc gac cac aag gca gat tcc cgg aca ctg tgc tga 1002
Val Arg Ala Asp His Lys Ala Asp Ser Arg Thr Leu Cys
325 330
<210> 24
<211> 333
<212> PRT
<213> 智人
<400> 24
Met Leu Thr Leu Thr Arg Ile Arg Thr Val Ser Tyr Glu Val Arg Ser
1 5 10 15
Thr Phe Leu Phe Ile Ser Val Leu Glu Phe Ala Val Gly Phe Leu Thr
20 25 30
Asn Ala Phe Val Phe Leu Val Asn Phe Trp Asp Val Val Lys Arg Gln
35 40 45
Pro Leu Ser Asn Ser Asp Cys Val Leu Leu Cys Leu Ser Ile Ser Arg
50 55 60
Leu Phe Leu His Gly Leu Leu Phe Leu Ser Ala Ile Gln Leu Thr His
65 70 75 80
Phe Gln Lys Leu Ser Glu Pro Leu Asn His Ser Tyr Gln Ala Ile Ile
85 90 95
Met Leu Trp Met Ile Ala Asn Gln Ala Asn Leu Trp Leu Ala Ala Cys
100 105 110
Leu Ser Leu Leu Tyr Cys Ser Lys Leu Ile Arg Phe Ser His Thr Phe
115 120 125
Leu Ile Cys Leu Ala Ser Trp Val Ser Arg Lys Ile Ser Gln Met Leu
130 135 140
Leu Gly Ile Ile Leu Cys Ser Cys Ile Cys Thr Val Leu Cys Val Trp
145 150 155 160
Cys Phe Phe Ser Arg Pro His Phe Thr Val Thr Thr Val Leu Phe Met
165 170 175
Asn Asn Asn Thr Arg Leu Asn Trp Gln Ile Lys Asp Leu Asn Leu Phe
180 185 190
Tyr Ser Phe Leu Phe Cys Tyr Leu Trp Ser Val Pro Pro Phe Leu Leu
195 200 205
Phe Leu Val Ser Ser Gly Met Leu Thr Val Ser Leu Gly Arg His Met
210 215 220
Arg Thr Met Lys Val Tyr Thr Arg Asn Ser Arg Asp Pro Ser Leu Glu
225 230 235 240
Ala His Ile Lys Ala Leu Lys Ser Leu Val Ser Phe Phe Cys Phe Phe
245 250 255
Val Ile Ser Ser Cys Ala Ala Phe Ile Ser Val Pro Leu Leu Ile Leu
260 265 270
Trp Arg Asp Lys Ile Gly Val Met Val Cys Val Gly Ile Met Ala Ala
275 280 285
Cys Pro Ser Gly His Ala Ala Val Leu Ile Ser Gly Asn Ala Lys Leu
290 295 300
Arg Arg Ala Val Met Thr Ile Leu Leu Trp Ala Gln Ser Ser Leu Lys
305 310 315 320
Val Arg Ala Asp His Lys Ala Asp Ser Arg Thr Leu Cys
325 330
<210> 25
<211> 1017
<212> DNA
<213> 智人
<220>
<221> CDS
<222> (1)..(1017)
<400> 25
atg cta ggg aga tgt ttt cct cca gac acc aaa gag aag caa cag ctc 48
Met Leu Gly Arg Cys Phe Pro Pro Asp Thr Lys Glu Lys Gln Gln Leu
1 5 10 15
aga atg act aaa ctc tgc gat cct gca gaa agt gaa ttg tcg cca ttt 96
Arg Met Thr Lys Leu Cys Asp Pro Ala Glu Ser Glu Leu Ser Pro Phe
20 25 30
ctc atc acc tta att tta gca gtt tta ctt gct gaa tac ctc att ggt 144
Leu Ile Thr Leu Ile Leu Ala Val Leu Leu Ala Glu Tyr Leu Ile Gly
35 40 45
atc att gca aat ggt ttc atc atg gct ata cat gca gct gaa tgg gtt 192
Ile Ile Ala Asn Gly Phe Ile Met Ala Ile His Ala Ala Glu Trp Val
50 55 60
caa aat aag gca gtt tcc aca agt ggc agg atc ctg gtt ttc ctg agt 240
Gln Asn Lys Ala Val Ser Thr Ser Gly Arg Ile Leu Val Phe Leu Ser
65 70 75 80
gta tcc aga ata gct ctc caa agc ctc atg atg tta gaa att acc atc 288
Val Ser Arg Ile Ala Leu Gln Ser Leu Met Met Leu Glu Ile Thr Ile
85 90 95
agc tca acc tcc cta agt ttt tat tct gaa gac gct gta tat tat gca 336
Ser Ser Thr Ser Leu Ser Phe Tyr Ser Glu Asp Ala Val Tyr Tyr Ala
100 105 110
ttc aaa ata agt ttt ata ttc tta aat ttt tgt agc ctg tgg ttt gct 384
Phe Lys Ile Ser Phe Ile Phe Leu Asn Phe Cys Ser Leu Trp Phe Ala
115 120 125
gcc tgg ctc agt ttc ttc tac ttt gtg aag att gcc aat ttc tcc tac 432
Ala Trp Leu Ser Phe Phe Tyr Phe Val Lys Ile Ala Asn Phe Ser Tyr
130 135 140
ccc ctt ttc ctc aaa ctg agg tgg aga att act gga ttg ata ccc tgg 480
Pro Leu Phe Leu Lys Leu Arg Trp Arg Ile Thr Gly Leu Ile Pro Trp
145 150 155 160
ctt ctg tgg ctg tcc gtg ttt att tcc ttc agt cac agc atg ttc tgc 528
Leu Leu Trp Leu Ser Val Phe Ile Ser Phe Ser His Ser Met Phe Cys
165 170 175
atc aac atc tgc act gtg tat tgt aac aat tct ttc cct atc cac tcc 576
Ile Asn Ile Cys Thr Val Tyr Cys Asn Asn Ser Phe Pro Ile His Ser
180 185 190
tcc aac tcc act aag aaa aca tac ttg tct gag atc aat gtg gtc ggt 624
Ser Asn Ser Thr Lys Lys Thr Tyr Leu Ser Glu Ile Asn Val Val Gly
195 200 205
ctg gct ttt ttc ttt aac ctg ggg att gtg act cct ctg atc atg ttc 672
Leu Ala Phe Phe Phe Asn Leu Gly Ile Val Thr Pro Leu Ile Met Phe
210 215 220
atc ctg aca gcc acc ctg ctg atc ctc tct ctc aag aga cac acc cta 720
Ile Leu Thr Ala Thr Leu Leu Ile Leu Ser Leu Lys Arg His Thr Leu
225 230 235 240
cac atg gga agc aat gcc aca ggg tcc aac gac ccc agc atg gag gct 768
His Met Gly Ser Asn Ala Thr Gly Ser Asn Asp Pro Ser Met Glu Ala
245 250 255
cac atg ggg gcc atc aaa gct atc agc tac ttt ctc att ctc tac att 816
His Met Gly Ala Ile Lys Ala Ile Ser Tyr Phe Leu Ile Leu Tyr Ile
260 265 270
ttc aat gca gtt gct ctg ttt atc tac ctg tcc aac atg ttt gac atc 864
Phe Asn Ala Val Ala Leu Phe Ile Tyr Leu Ser Asn Met Phe Asp Ile
275 280 285
aac agt ctg tgg aat aat ttg tgc cag atc atc atg gct gcc tac cct 912
Asn Ser Leu Trp Asn Asn Leu Cys Gln Ile Ile Met Ala Ala Tyr Pro
290 295 300
gcc agc cac tca att cta ctg att caa gat aac cct ggg ctg aga aga 960
Ala Ser His Ser Ile Leu Leu Ile Gln Asp Asn Pro Gly Leu Arg Arg
305 310 315 320
gcc tgg aag cgg ctt cag ctt cga ctt cat ctt tac cca aaa gag tgg 1008
Ala Trp Lys Arg Leu Gln Leu Arg Leu His Leu Tyr Pro Lys Glu Trp
325 330 335
act ctg tga 1017
Thr Leu
<210> 26
<211> 338
<212> PRT
<213> 智人
<400> 26
Met Leu Gly Arg Cys Phe Pro Pro Asp Thr Lys Glu Lys Gln Gln Leu
1 5 10 15
Arg Met Thr Lys Leu Cys Asp Pro Ala Glu Ser Glu Leu Ser Pro Phe
20 25 30
Leu Ile Thr Leu Ile Leu Ala Val Leu Leu Ala Glu Tyr Leu Ile Gly
35 40 45
Ile Ile Ala Asn Gly Phe Ile Met Ala Ile His Ala Ala Glu Trp Val
50 55 60
Gln Asn Lys Ala Val Ser Thr Ser Gly Arg Ile Leu Val Phe Leu Ser
65 70 75 80
Val Ser Arg Ile Ala Leu Gln Ser Leu Met Met Leu Glu Ile Thr Ile
85 90 95
Ser Ser Thr Ser Leu Ser Phe Tyr Ser Glu Asp Ala Val Tyr Tyr Ala
100 105 110
Phe Lys Ile Ser Phe Ile Phe Leu Asn Phe Cys Ser Leu Trp Phe Ala
115 120 125
Ala Trp Leu Ser Phe Phe Tyr Phe Val Lys Ile Ala Asn Phe Ser Tyr
130 135 140
Pro Leu Phe Leu Lys Leu Arg Trp Arg Ile Thr Gly Leu Ile Pro Trp
145 150 155 160
Leu Leu Trp Leu Ser Val Phe Ile Ser Phe Ser His Ser Met Phe Cys
165 170 175
Ile Asn Ile Cys Thr Val Tyr Cys Asn Asn Ser Phe Pro Ile His Ser
180 185 190
Ser Asn Ser Thr Lys Lys Thr Tyr Leu Ser Glu Ile Asn Val Val Gly
195 200 205
Leu Ala Phe Phe Phe Asn Leu Gly Ile Val Thr Pro Leu Ile Met Phe
210 215 220
Ile Leu Thr Ala Thr Leu Leu Ile Leu Ser Leu Lys Arg His Thr Leu
225 230 235 240
His Met Gly Ser Asn Ala Thr Gly Ser Asn Asp Pro Ser Met Glu Ala
245 250 255
His Met Gly Ala Ile Lys Ala Ile Ser Tyr Phe Leu Ile Leu Tyr Ile
260 265 270
Phe Asn Ala Val Ala Leu Phe Ile Tyr Leu Ser Asn Met Phe Asp Ile
275 280 285
Asn Ser Leu Trp Asn Asn Leu Cys Gln Ile Ile Met Ala Ala Tyr Pro
290 295 300
Ala Ser His Ser Ile Leu Leu Ile Gln Asp Asn Pro Gly Leu Arg Arg
305 310 315 320
Ala Trp Lys Arg Leu Gln Leu Arg Leu His Leu Tyr Pro Lys Glu Trp
325 330 335
Thr Leu
<210> 27
<211> 972
<212> DNA
<213> 智人
<220>
<221> CDS
<222> (1)..(972)
<400> 27
atg gca acg gtg aac aca gat gcc aca gat aaa gac ata tcc aag ttc 48
Met Ala Thr Val Asn Thr Asp Ala Thr Asp Lys Asp Ile Ser Lys Phe
1 5 10 15
aag gtc acc ttc act ttg gtg gtc tcc gga ata gag tgc atc act ggc 96
Lys Val Thr Phe Thr Leu Val Val Ser Gly Ile Glu Cys Ile Thr Gly
20 25 30
atc ctt ggg agt ggc ttc atc acg gcc atc tat ggg gct gag tgg gcc 144
Ile Leu Gly Ser Gly Phe Ile Thr Ala Ile Tyr Gly Ala Glu Trp Ala
35 40 45
agg ggc aaa aca ctc ccc act ggt gac cgc att atg ttg atg ctg agc 192
Arg Gly Lys Thr Leu Pro Thr Gly Asp Arg Ile Met Leu Met Leu Ser
50 55 60
ttt tcc agg ctc ttg cta cag att tgg atg atg ctg gag aac att ttc 240
Phe Ser Arg Leu Leu Leu Gln Ile Trp Met Met Leu Glu Asn Ile Phe
65 70 75 80
agt ctg cta ttc cga att gtt tat aac caa aac tca gtg tat atc ctc 288
Ser Leu Leu Phe Arg Ile Val Tyr Asn Gln Asn Ser Val Tyr Ile Leu
85 90 95
ttc aaa gtc atc act gtc ttt ctg aac cat tcc aat ctc tgg ttt gct 336
Phe Lys Val Ile Thr Val Phe Leu Asn His Ser Asn Leu Trp Phe Ala
100 105 110
gcc tgg ctc aaa gtc ttc tat tgt ctt aga att gca aac ttc aat cat 384
Ala Trp Leu Lys Val Phe Tyr Cys Leu Arg Ile Ala Asn Phe Asn His
115 120 125
cct ttg ttc ttc ctg atg aag agg aaa atc ata gtg ctg atg cct tgg 432
Pro Leu Phe Phe Leu Met Lys Arg Lys Ile Ile Val Leu Met Pro Trp
130 135 140
ctt ctc agg ctg tca gtg ttg gtt tcc tta agc ttc agc ttt cct ctc 480
Leu Leu Arg Leu Ser Val Leu Val Ser Leu Ser Phe Ser Phe Pro Leu
145 150 155 160
tcg aga gat gtc ttc aat gtg tat gtg aat agc tcc att cct atc ccc 528
Ser Arg Asp Val Phe Asn Val Tyr Val Asn Ser Ser Ile Pro Ile Pro
165 170 175
tcc tcc aac tcc acg gag aag aag tac ttc tct gag acc aat atg gtc 576
Ser Ser Asn Ser Thr Glu Lys Lys Tyr Phe Ser Glu Thr Asn Met Val
180 185 190
aac ctg gta ttt ttc tat aac atg ggg atc ttc gtt cct ctg atc atg 624
Asn Leu Val Phe Phe Tyr Asn Met Gly Ile Phe Val Pro Leu Ile Met
195 200 205
ttc atc ctg gca gcc acc ctg ctg atc ctc tct ctc aag aga cac acc 672
Phe Ile Leu Ala Ala Thr Leu Leu Ile Leu Ser Leu Lys Arg His Thr
210 215 220
cta cac atg gga agc aat gcc aca ggg tcc agg gac ccc agc atg aag 720
Leu His Met Gly Ser Asn Ala Thr Gly Ser Arg Asp Pro Ser Met Lys
225 230 235 240
gct cac ata ggg gcc atc aaa gcc acc agc tac ttt ctc atc ctc tac 768
Ala His Ile Gly Ala Ile Lys Ala Thr Ser Tyr Phe Leu Ile Leu Tyr
245 250 255
att ttc aat gca att gct cta ttt ctt tcc acg tcc aac atc ttt gac 816
Ile Phe Asn Ala Ile Ala Leu Phe Leu Ser Thr Ser Asn Ile Phe Asp
260 265 270
act tac agt tcc tgg aat att ttg tgc aag atc atc atg gct gcc tac 864
Thr Tyr Ser Ser Trp Asn Ile Leu Cys Lys Ile Ile Met Ala Ala Tyr
275 280 285
cct gcc ggc cac tca gta caa ctg atc ttg ggc aac cct ggg ctg aga 912
Pro Ala Gly His Ser Val Gln Leu Ile Leu Gly Asn Pro Gly Leu Arg
290 295 300
aga gcc tgg aag cgg ttt cag cac caa gtt cct ctt tac cta aaa ggg 960
Arg Ala Trp Lys Arg Phe Gln His Gln Val Pro Leu Tyr Leu Lys Gly
305 310 315 320
cag act ctg tga 972
Gln Thr Leu
<210> 28
<211> 323
<212> PRT
<213> 智人
<400> 28
Met Ala Thr Val Asn Thr Asp Ala Thr Asp Lys Asp Ile Ser Lys Phe
1 5 10 15
Lys Val Thr Phe Thr Leu Val Val Ser Gly Ile Glu Cys Ile Thr Gly
20 25 30
Ile Leu Gly Ser Gly Phe Ile Thr Ala Ile Tyr Gly Ala Glu Trp Ala
35 40 45
Arg Gly Lys Thr Leu Pro Thr Gly Asp Arg Ile Met Leu Met Leu Ser
50 55 60
Phe Ser Arg Leu Leu Leu Gln Ile Trp Met Met Leu Glu Asn Ile Phe
65 70 75 80
Ser Leu Leu Phe Arg Ile Val Tyr Asn Gln Asn Ser Val Tyr Ile Leu
85 90 95
Phe Lys Val Ile Thr Val Phe Leu Asn His Ser Asn Leu Trp Phe Ala
100 105 110
Ala Trp Leu Lys Val Phe Tyr Cys Leu Arg Ile Ala Asn Phe Asn His
115 120 125
Pro Leu Phe Phe Leu Met Lys Arg Lys Ile Ile Val Leu Met Pro Trp
130 135 140
Leu Leu Arg Leu Ser Val Leu Val Ser Leu Ser Phe Ser Phe Pro Leu
145 150 155 160
Ser Arg Asp Val Phe Asn Val Tyr Val Asn Ser Ser Ile Pro Ile Pro
165 170 175
Ser Ser Asn Ser Thr Glu Lys Lys Tyr Phe Ser Glu Thr Asn Met Val
180 185 190
Asn Leu Val Phe Phe Tyr Asn Met Gly Ile Phe Val Pro Leu Ile Met
195 200 205
Phe Ile Leu Ala Ala Thr Leu Leu Ile Leu Ser Leu Lys Arg His Thr
210 215 220
Leu His Met Gly Ser Asn Ala Thr Gly Ser Arg Asp Pro Ser Met Lys
225 230 235 240
Ala His Ile Gly Ala Ile Lys Ala Thr Ser Tyr Phe Leu Ile Leu Tyr
245 250 255
Ile Phe Asn Ala Ile Ala Leu Phe Leu Ser Thr Ser Asn Ile Phe Asp
260 265 270
Thr Tyr Ser Ser Trp Asn Ile Leu Cys Lys Ile Ile Met Ala Ala Tyr
275 280 285
Pro Ala Gly His Ser Val Gln Leu Ile Leu Gly Asn Pro Gly Leu Arg
290 295 300
Arg Ala Trp Lys Arg Phe Gln His Gln Val Pro Leu Tyr Leu Lys Gly
305 310 315 320
Gln Thr Leu
<210> 29
<211> 924
<212> DNA
<213> 智人
<220>
<221> CDS
<222> (1)..(924)
<400> 29
atg caa gca gca ctg acg gcc ttc ttc gtg ttg ctc ttt agc ctg ctg 48
Met Gln Ala Ala Leu Thr Ala Phe Phe Val Leu Leu Phe Ser Leu Leu
1 5 10 15
agt ctt ctg ggg att gca gcg aat ggc ttc att gtg ctg gtg ctg ggc 96
Ser Leu Leu Gly Ile Ala Ala Asn Gly Phe Ile Val Leu Val Leu Gly
20 25 30
agg gag tgg ctg cga tat ggc agg ttg ctg ccc ttg gat atg atc ctc 144
Arg Glu Trp Leu Arg Tyr Gly Arg Leu Leu Pro Leu Asp Met Ile Leu
35 40 45
att agc ttg ggt gcc tcc cgc ttc tgc ctg cag ttg gtt ggg aca gtg 192
Ile Ser Leu Gly Ala Ser Arg Phe Cys Leu Gln Leu Val Gly Thr Val
50 55 60
cac aac ttc tac tac tct gcc cag aag gtc gag tac tct ggg ggt ctc 240
His Asn Phe Tyr Tyr Ser Ala Gln Lys Val Glu Tyr Ser Gly Gly Leu
65 70 75 80
ggc cga cag ttc ttc cat cta cac tgg cac ttc ctg aac tca gcc acc 288
Gly Arg Gln Phe Phe His Leu His Trp His Phe Leu Asn Ser Ala Thr
85 90 95
ttc tgg ttt tgc agc tgg ctc agt gtc ctg ttc tgt gtg aag att gct 336
Phe Trp Phe Cys Ser Trp Leu Ser Val Leu Phe Cys Val Lys Ile Ala
100 105 110
aac atc aca cac tcc acc ttc ctg tgg ctg aag tgg agg ttc cta ggg 384
Asn Ile Thr His Ser Thr Phe Leu Trp Leu Lys Trp Arg Phe Leu Gly
115 120 125
tgg gtg ccc tgg ctc ctg ttg ggc tct gtc ctg atc tcc ttc atc ata 432
Trp Val Pro Trp Leu Leu Leu Gly Ser Val Leu Ile Ser Phe Ile Ile
130 135 140
acc ctg ctg ttt ttt tgg gtg aac tac cct gta tat caa gaa ttt tta 480
Thr Leu Leu Phe Phe Trp Val Asn Tyr Pro Val Tyr Gln Glu Phe Leu
145 150 155 160
att aga aaa ttt tct ggg aac atg acc tac aag tgg aat aca agg ata 528
Ile Arg Lys Phe Ser Gly Asn Met Thr Tyr Lys Trp Asn Thr Arg Ile
165 170 175
gaa aca tac tat ttc cca tcc ctg aaa ctg gtc atc tgg tca att cct 576
Glu Thr Tyr Tyr Phe Pro Ser Leu Lys Leu Val Ile Trp Ser Ile Pro
180 185 190
ttt tct gtt ttt ctg gtc tca att atg ctg tta att aat tct ctg agg 624
Phe Ser Val Phe Leu Val Ser Ile Met Leu Leu Ile Asn Ser Leu Arg
195 200 205
agg cat act cag aga atg cag cac aac ggg cac agc ctg cag gac ccc 672
Arg His Thr Gln Arg Met Gln His Asn Gly His Ser Leu Gln Asp Pro
210 215 220
agc acc cag gct cac acc aga gct ctg aag tcc ctc atc tcc ttc ctc 720
Ser Thr Gln Ala His Thr Arg Ala Leu Lys Ser Leu Ile Ser Phe Leu
225 230 235 240
att ctt tat gct ctg tcc ttt ctg tcc ctg atc att gat gcc gca aaa 768
Ile Leu Tyr Ala Leu Ser Phe Leu Ser Leu Ile Ile Asp Ala Ala Lys
245 250 255
ttt atc tcc atg cag aac gac ttt tac tgg cca tgg caa att gca gtc 816
Phe Ile Ser Met Gln Asn Asp Phe Tyr Trp Pro Trp Gln Ile Ala Val
260 265 270
tac ctg tgc ata tct gtc cat ccc ttc atc ctc atc ttc agc aac ctc 864
Tyr Leu Cys Ile Ser Val His Pro Phe Ile Leu Ile Phe Ser Asn Leu
275 280 285
aag ctt cga agc gtg ttc tca cag ctc ctg ttg ttg gca agg ggc ttc 912
Lys Leu Arg Ser Val Phe Ser Gln Leu Leu Leu Leu Ala Arg Gly Phe
290 295 300
tgg gtg gcc tga 924
Trp Val Ala
305
<210> 30
<211> 307
<212> PRT
<213> 智人
<400> 30
Met Gln Ala Ala Leu Thr Ala Phe Phe Val Leu Leu Phe Ser Leu Leu
1 5 10 15
Ser Leu Leu Gly Ile Ala Ala Asn Gly Phe Ile Val Leu Val Leu Gly
20 25 30
Arg Glu Trp Leu Arg Tyr Gly Arg Leu Leu Pro Leu Asp Met Ile Leu
35 40 45
Ile Ser Leu Gly Ala Ser Arg Phe Cys Leu Gln Leu Val Gly Thr Val
50 55 60
His Asn Phe Tyr Tyr Ser Ala Gln Lys Val Glu Tyr Ser Gly Gly Leu
65 70 75 80
Gly Arg Gln Phe Phe His Leu His Trp His Phe Leu Asn Ser Ala Thr
85 90 95
Phe Trp Phe Cys Ser Trp Leu Ser Val Leu Phe Cys Val Lys Ile Ala
100 105 110
Asn Ile Thr His Ser Thr Phe Leu Trp Leu Lys Trp Arg Phe Leu Gly
115 120 125
Trp Val Pro Trp Leu Leu Leu Gly Ser Val Leu Ile Ser Phe Ile Ile
130 135 140
Thr Leu Leu Phe Phe Trp Val Asn Tyr Pro Val Tyr Gln Glu Phe Leu
145 150 155 160
Ile Arg Lys Phe Ser Gly Asn Met Thr Tyr Lys Trp Asn Thr Arg Ile
165 170 175
Glu Thr Tyr Tyr Phe Pro Ser Leu Lys Leu Val Ile Trp Ser Ile Pro
180 185 190
Phe Ser Val Phe Leu Val Ser Ile Met Leu Leu Ile Asn Ser Leu Arg
195 200 205
Arg His Thr Gln Arg Met Gln His Asn Gly His Ser Leu Gln Asp Pro
210 215 220
Ser Thr Gln Ala His Thr Arg Ala Leu Lys Ser Leu Ile Ser Phe Leu
225 230 235 240
Ile Leu Tyr Ala Leu Ser Phe Leu Ser Leu Ile Ile Asp Ala Ala Lys
245 250 255
Phe Ile Ser Met Gln Asn Asp Phe Tyr Trp Pro Trp Gln Ile Ala Val
260 265 270
Tyr Leu Cys Ile Ser Val His Pro Phe Ile Leu Ile Phe Ser Asn Leu
275 280 285
Lys Leu Arg Ser Val Phe Ser Gln Leu Leu Leu Leu Ala Arg Gly Phe
290 295 300
Trp Val Ala
305
<210> 31
<211> 945
<212> DNA
<213> 智人
<220>
<221> CDS
<222> (1)..(945)
<400> 31
atg gcc acc gaa ttg gac aaa atc ttt ctg att ctg gca ata gca gaa 48
Met Ala Thr Glu Leu Asp Lys Ile Phe Leu Ile Leu Ala Ile Ala Glu
1 5 10 15
ttc atc atc agc atg ctg ggg aat gtg ttc att gga ctg gta aac tgc 96
Phe Ile Ile Ser Met Leu Gly Asn Val Phe Ile Gly Leu Val Asn Cys
20 25 30
tct gaa ggg atc aag aac caa aag gtc ttc tca gct gac ttc atc ctc 144
Ser Glu Gly Ile Lys Asn Gln Lys Val Phe Ser Ala Asp Phe Ile Leu
35 40 45
acc tgc ttg gct atc tcc aca att gga caa ctg ttg gtg ata ctg ttt 192
Thr Cys Leu Ala Ile Ser Thr Ile Gly Gln Leu Leu Val Ile Leu Phe
50 55 60
gat tca ttt cta gtg gga ctt gct tca cat tta tat acc aca tat aga 240
Asp Ser Phe Leu Val Gly Leu Ala Ser His Leu Tyr Thr Thr Tyr Arg
65 70 75 80
cta gga aaa act gtt att atg ctt tgg cac atg act aat cac ttg aca 288
Leu Gly Lys Thr Val Ile Met Leu Trp His Met Thr Asn His Leu Thr
85 90 95
acc tgg ctt gcc acc tgc cta agc att ttc tat ttc ttt aag ata gcc 336
Thr Trp Leu Ala Thr Cys Leu Ser Ile Phe Tyr Phe Phe Lys Ile Ala
100 105 110
cac ttc ccc cac tcc ctt ttc ctc tgg ctg agg tgg agg atg aac gga 384
His Phe Pro His Ser Leu Phe Leu Trp Leu Arg Trp Arg Met Asn Gly
115 120 125
atg att gtt atg ctt ctt ata ttg tct ttg ttc tta ctg att ttt gac 432
Met Ile Val Met Leu Leu Ile Leu Ser Leu Phe Leu Leu Ile Phe Asp
130 135 140
agt tta gtg cta gaa ata ttt att gat atc tca ctc aat ata ata gat 480
Ser Leu Val Leu Glu Ile Phe Ile Asp Ile Ser Leu Asn Ile Ile Asp
145 150 155 160
aaa agt aat ctg act tta tat tta gat gaa agt aaa act ctc tat gat 528
Lys Ser Asn Leu Thr Leu Tyr Leu Asp Glu Ser Lys Thr Leu Tyr Asp
165 170 175
aaa ctc tct att tta aaa act ctt ctc agc tta acc agt ttt atc ccc 576
Lys Leu Ser Ile Leu Lys Thr Leu Leu Ser Leu Thr Ser Phe Ile Pro
180 185 190
ttt tct ctg ttc ctg acc tcc ttg ctt ttt tta ttt ctg tcc ttg gtg 624
Phe Ser Leu Phe Leu Thr Ser Leu Leu Phe Leu Phe Leu Ser Leu Val
195 200 205
aga cat act aga aat ttg aag ctc agt tcc ttg ggc tct aga gac tcc 672
Arg His Thr Arg Asn Leu Lys Leu Ser Ser Leu Gly Ser Arg Asp Ser
210 215 220
agc aca gag gcc cat agg agg gcc atg aaa atg gtg atg tct ttc ctt 720
Ser Thr Glu Ala His Arg Arg Ala Met Lys Met Val Met Ser Phe Leu
225 230 235 240
ttc ctc ttc ata gtt cat ttt ttt tcc tta caa gtg gcc aat ggg ata 768
Phe Leu Phe Ile Val His Phe Phe Ser Leu Gln Val Ala Asn Gly Ile
245 250 255
ttt ttt atg ttg tgg aac aac aag tac ata aag ttt gtc atg tta gcc 816
Phe Phe Met Leu Trp Asn Asn Lys Tyr Ile Lys Phe Val Met Leu Ala
260 265 270
tta aat gcc ttt ccc tcg tgc cac tca ttt att ctc att ctg gga aac 864
Leu Asn Ala Phe Pro Ser Cys His Ser Phe Ile Leu Ile Leu Gly Asn
275 280 285
agc aag ctg cga cag aca gct gtg agg cta ctg tgg cat ctt agg aac 912
Ser Lys Leu Arg Gln Thr Ala Val Arg Leu Leu Trp His Leu Arg Asn
290 295 300
tat aca aaa aca cca aat gct tta cct ttg tag 945
Tyr Thr Lys Thr Pro Asn Ala Leu Pro Leu
305 310
<210> 32
<211> 314
<212> PRT
<213> 智人
<400> 32
Met Ala Thr Glu Leu Asp Lys Ile Phe Leu Ile Leu Ala Ile Ala Glu
1 5 10 15
Phe Ile Ile Ser Met Leu Gly Asn Val Phe Ile Gly Leu Val Asn Cys
20 25 30
Ser Glu Gly Ile Lys Asn Gln Lys Val Phe Ser Ala Asp Phe Ile Leu
35 40 45
Thr Cys Leu Ala Ile Ser Thr Ile Gly Gln Leu Leu Val Ile Leu Phe
50 55 60
Asp Ser Phe Leu Val Gly Leu Ala Ser His Leu Tyr Thr Thr Tyr Arg
65 70 75 80
Leu Gly Lys Thr Val Ile Met Leu Trp His Met Thr Asn His Leu Thr
85 90 95
Thr Trp Leu Ala Thr Cys Leu Ser Ile Phe Tyr Phe Phe Lys Ile Ala
100 105 110
His Phe Pro His Ser Leu Phe Leu Trp Leu Arg Trp Arg Met Asn Gly
115 120 125
Met Ile Val Met Leu Leu Ile Leu Ser Leu Phe Leu Leu Ile Phe Asp
130 135 140
Ser Leu Val Leu Glu Ile Phe Ile Asp Ile Ser Leu Asn Ile Ile Asp
145 150 155 160
Lys Ser Asn Leu Thr Leu Tyr Leu Asp Glu Ser Lys Thr Leu Tyr Asp
165 170 175
Lys Leu Ser Ile Leu Lys Thr Leu Leu Ser Leu Thr Ser Phe Ile Pro
180 185 190
Phe Ser Leu Phe Leu Thr Ser Leu Leu Phe Leu Phe Leu Ser Leu Val
195 200 205
Arg His Thr Arg Asn Leu Lys Leu Ser Ser Leu Gly Ser Arg Asp Ser
210 215 220
Ser Thr Glu Ala His Arg Arg Ala Met Lys Met Val Met Ser Phe Leu
225 230 235 240
Phe Leu Phe Ile Val His Phe Phe Ser Leu Gln Val Ala Asn Gly Ile
245 250 255
Phe Phe Met Leu Trp Asn Asn Lys Tyr Ile Lys Phe Val Met Leu Ala
260 265 270
Leu Asn Ala Phe Pro Ser Cys His Ser Phe Ile Leu Ile Leu Gly Asn
275 280 285
Ser Lys Leu Arg Gln Thr Ala Val Arg Leu Leu Trp His Leu Arg Asn
290 295 300
Tyr Thr Lys Thr Pro Asn Ala Leu Pro Leu
305 310
<210> 33
<211> 930
<212> DNA
<213> 智人
<220>
<221> CDS
<222> (1)..(930)
<400> 33
atg ata act ttt cta ccc atc att ttt tcc agt ctg gta gtg gtt aca 48
Met Ile Thr Phe Leu Pro Ile Ile Phe Ser Ser Leu Val Val Val Thr
1 5 10 15
ttt gtt att gga aat ttt gct aat ggc ttc ata gca ctg gta aat tcc 96
Phe Val Ile Gly Asn Phe Ala Asn Gly Phe Ile Ala Leu Val Asn Ser
20 25 30
att gag tcg ttc aag aga caa aag atc tcc ttt gct gac caa att ctc 144
Ile Glu Ser Phe Lys Arg Gln Lys Ile Ser Phe Ala Asp Gln Ile Leu
35 40 45
act gct ctg gcg gtc tcc aga gtt ggt ttg ctc tgg gta tta tta tta 192
Thr Ala Leu Ala Val Ser Arg Val Gly Leu Leu Trp Val Leu Leu Leu
50 55 60
aac tgg tat tca act gtg ttg aat cca gct ttt aat agt gta gaa gta 240
Asn Trp Tyr Ser Thr Val Leu Asn Pro Ala Phe Asn Ser Val Glu Val
65 70 75 80
aga act act gct tat aat atc tgg gca gtg atc aac cat ttc agc aac 288
Arg Thr Thr Ala Tyr Asn Ile Trp Ala Val Ile Asn His Phe Ser Asn
85 90 95
tgg ctt gct act acc ctc agc ata ttt tat ttg ctc aag att gcc aat 336
Trp Leu Ala Thr Thr Leu Ser Ile Phe Tyr Leu Leu Lys Ile Ala Asn
100 105 110
ttc tcc aac ttt att ttt ctt cac tta aag agg aga gtt aag agt gtc 384
Phe Ser Asn Phe Ile Phe Leu His Leu Lys Arg Arg Val Lys Ser Val
115 120 125
att ctg gtg atg ttg ttg ggg cct ttg cta ttt ttg gct tgt cat ctt 432
Ile Leu Val Met Leu Leu Gly Pro Leu Leu Phe Leu Ala Cys His Leu
130 135 140
ttt gtg ata aac atg aat gag att gtg cgg aca aaa gaa ttt gaa gga 480
Phe Val Ile Asn Met Asn Glu Ile Val Arg Thr Lys Glu Phe Glu Gly
145 150 155 160
aac atg act tgg aag atc aaa ttg aag agt gca atg tac ttt tca aat 528
Asn Met Thr Trp Lys Ile Lys Leu Lys Ser Ala Met Tyr Phe Ser Asn
165 170 175
atg act gta acc atg gta gca aac tta gta ccc ttc act ctg acc cta 576
Met Thr Val Thr Met Val Ala Asn Leu Val Pro Phe Thr Leu Thr Leu
180 185 190
cta tct ttt atg ctg tta atc tgt tct ttg tgt aaa cat ctc aag aag 624
Leu Ser Phe Met Leu Leu Ile Cys Ser Leu Cys Lys His Leu Lys Lys
195 200 205
atg cag ctc cgt ggt aaa gga tct caa gat ccc agc acg aag gtc cac 672
Met Gln Leu Arg Gly Lys Gly Ser Gln Asp Pro Ser Thr Lys Val His
210 215 220
ata aaa gct ttg caa act gtg atc tcc ttc ctc ttg tta tgt gcc att 720
Ile Lys Ala Leu Gln Thr Val Ile Ser Phe Leu Leu Leu Cys Ala Ile
225 230 235 240
tac ttt ctg tcc ata atg ata tca gtt tgg agt ttt gga agt ctg gaa 768
Tyr Phe Leu Ser Ile Met Ile Ser Val Trp Ser Phe Gly Ser Leu Glu
245 250 255
aac aaa cct gtc ttc atg ttc tgc aaa gct att aga ttc agc tat cct 816
Asn Lys Pro Val Phe Met Phe Cys Lys Ala Ile Arg Phe Ser Tyr Pro
260 265 270
tca atc cac cca ttc atc ctg att tgg gga aac aag aag cta aag cag 864
Ser Ile His Pro Phe Ile Leu Ile Trp Gly Asn Lys Lys Leu Lys Gln
275 280 285
act ttt ctt tca gtt ttt tgg caa atg agg tac tgg gtg aaa gga gag 912
Thr Phe Leu Ser Val Phe Trp Gln Met Arg Tyr Trp Val Lys Gly Glu
290 295 300
aag act tca tct cca tag 930
Lys Thr Ser Ser Pro
305
<210> 34
<211> 309
<212> PRT
<213> 智人
<400> 34
Met Ile Thr Phe Leu Pro Ile Ile Phe Ser Ser Leu Val Val Val Thr
1 5 10 15
Phe Val Ile Gly Asn Phe Ala Asn Gly Phe Ile Ala Leu Val Asn Ser
20 25 30
Ile Glu Ser Phe Lys Arg Gln Lys Ile Ser Phe Ala Asp Gln Ile Leu
35 40 45
Thr Ala Leu Ala Val Ser Arg Val Gly Leu Leu Trp Val Leu Leu Leu
50 55 60
Asn Trp Tyr Ser Thr Val Leu Asn Pro Ala Phe Asn Ser Val Glu Val
65 70 75 80
Arg Thr Thr Ala Tyr Asn Ile Trp Ala Val Ile Asn His Phe Ser Asn
85 90 95
Trp Leu Ala Thr Thr Leu Ser Ile Phe Tyr Leu Leu Lys Ile Ala Asn
100 105 110
Phe Ser Asn Phe Ile Phe Leu His Leu Lys Arg Arg Val Lys Ser Val
115 120 125
Ile Leu Val Met Leu Leu Gly Pro Leu Leu Phe Leu Ala Cys His Leu
130 135 140
Phe Val Ile Asn Met Asn Glu Ile Val Arg Thr Lys Glu Phe Glu Gly
145 150 155 160
Asn Met Thr Trp Lys Ile Lys Leu Lys Ser Ala Met Tyr Phe Ser Asn
165 170 175
Met Thr Val Thr Met Val Ala Asn Leu Val Pro Phe Thr Leu Thr Leu
180 185 190
Leu Ser Phe Met Leu Leu Ile Cys Ser Leu Cys Lys His Leu Lys Lys
195 200 205
Met Gln Leu Arg Gly Lys Gly Ser Gln Asp Pro Ser Thr Lys Val His
210 215 220
Ile Lys Ala Leu Gln Thr Val Ile Ser Phe Leu Leu Leu Cys Ala Ile
225 230 235 240
Tyr Phe Leu Ser Ile Met Ile Ser Val Trp Ser Phe Gly Ser Leu Glu
245 250 255
Asn Lys Pro Val Phe Met Phe Cys Lys Ala Ile Arg Phe Ser Tyr Pro
260 265 270
Ser Ile His Pro Phe Ile Leu Ile Trp Gly Asn Lys Lys Leu Lys Gln
275 280 285
Thr Phe Leu Ser Val Phe Trp Gln Met Arg Tyr Trp Val Lys Gly Glu
290 295 300
Lys Thr Ser Ser Pro
305
<210> 35
<211> 930
<212> DNA
<213> 智人
<220>
<221> CDS
<222> (1)..(930)
<400> 35
atg aca act ttt ata ccc atc att ttt tcc agt gtg gta gtg gtt cta 48
Met Thr Thr Phe Ile Pro Ile Ile Phe Ser Ser Val Val Val Val Leu
1 5 10 15
ttt gtt att gga aat ttt gct aat ggc ttc ata gca ttg gta aat tcc 96
Phe Val Ile Gly Asn Phe Ala Asn Gly Phe Ile Ala Leu Val Asn Ser
20 25 30
att gag cgg gtc aag aga caa aag atc tct ttt gct gac cag att ctc 144
Ile Glu Arg Val Lys Arg Gln Lys Ile Ser Phe Ala Asp Gln Ile Leu
35 40 45
act gct ctg gcg gtc tcc aga gtt ggt ttg ctc tgg gta tta tta tta 192
Thr Ala Leu Ala Val Ser Arg Val Gly Leu Leu Trp Val Leu Leu Leu
50 55 60
aat tgg tat tca act gtg ttt aat cca gct ttt tat agt gta gaa gta 240
Asn Trp Tyr Ser Thr Val Phe Asn Pro Ala Phe Tyr Ser Val Glu Val
65 70 75 80
aga act act gct tat aat gtc tgg gca gta acc ggc cat ttc agc aac 288
Arg Thr Thr Ala Tyr Asn Val Trp Ala Val Thr Gly His Phe Ser Asn
85 90 95
tgg ctt gct act agc ctc agc ata ttt tat ttg ctc aag att gcc aat 336
Trp Leu Ala Thr Ser Leu Ser Ile Phe Tyr Leu Leu Lys Ile Ala Asn
100 105 110
ttc tcc aac ctt att ttt ctt cac tta aag agg aga gtt aag agt gtc 384
Phe Ser Asn Leu Ile Phe Leu His Leu Lys Arg Arg Val Lys Ser Val
115 120 125
att ctg gtg atg ctg ttg ggg cct tta cta ttt ttg gct tgt caa ctt 432
Ile Leu Val Met Leu Leu Gly Pro Leu Leu Phe Leu Ala Cys Gln Leu
130 135 140
ttt gtg ata aac atg aaa gag att gta cgg aca aaa gaa tat gaa gga 480
Phe Val Ile Asn Met Lys Glu Ile Val Arg Thr Lys Glu Tyr Glu Gly
145 150 155 160
aac atg act tgg aag atc aaa ttg agg agt gca gtg tac ctt tca gat 528
Asn Met Thr Trp Lys Ile Lys Leu Arg Ser Ala Val Tyr Leu Ser Asp
165 170 175
gcg act gta acc acg cta gga aac tta gtg ccc ttc act ctg acc ctg 576
Ala Thr Val Thr Thr Leu Gly Asn Leu Val Pro Phe Thr Leu Thr Leu
180 185 190
cta tgt ttt ttg ctg tta atc tgt tct ctg tgt aaa cat ctc aag aag 624
Leu Cys Phe Leu Leu Leu Ile Cys Ser Leu Cys Lys His Leu Lys Lys
195 200 205
atg cag ctc cat ggt aaa gga tct caa gat ccc agc acc aag gtc cac 672
Met Gln Leu His Gly Lys Gly Ser Gln Asp Pro Ser Thr Lys Val His
210 215 220
ata aaa gct ttg caa act gtg atc ttt ttc ctc ttg tta tgt gcc gtt 720
Ile Lys Ala Leu Gln Thr Val Ile Phe Phe Leu Leu Leu Cys Ala Val
225 230 235 240
tac ttt ctg tcc ata atg ata tca gtt tgg agt ttt ggg agt ctg gaa 768
Tyr Phe Leu Ser Ile Met Ile Ser Val Trp Ser Phe Gly Ser Leu Glu
245 250 255
aac aaa cct gtc ttc atg ttc tgc aaa gct att aga ttc agc tat cct 816
Asn Lys Pro Val Phe Met Phe Cys Lys Ala Ile Arg Phe Ser Tyr Pro
260 265 270
tca atc cac cca ttc atc ctg att tgg gga aac aag aag cta aag cag 864
Ser Ile His Pro Phe Ile Leu Ile Trp Gly Asn Lys Lys Leu Lys Gln
275 280 285
act ttt ctt tca gtt ttg cgg caa gtg agg tac tgg gtg aaa gga gag 912
Thr Phe Leu Ser Val Leu Arg Gln Val Arg Tyr Trp Val Lys Gly Glu
290 295 300
aag cct tca tct cca tga 930
Lys Pro Ser Ser Pro
305
<210> 36
<211> 309
<212> PRT
<213> 智人
<400> 36
Met Thr Thr Phe Ile Pro Ile Ile Phe Ser Ser Val Val Val Val Leu
1 5 10 15
Phe Val Ile Gly Asn Phe Ala Asn Gly Phe Ile Ala Leu Val Asn Ser
20 25 30
Ile Glu Arg Val Lys Arg Gln Lys Ile Ser Phe Ala Asp Gln Ile Leu
35 40 45
Thr Ala Leu Ala Val Ser Arg Val Gly Leu Leu Trp Val Leu Leu Leu
50 55 60
Asn Trp Tyr Ser Thr Val Phe Asn Pro Ala Phe Tyr Ser Val Glu Val
65 70 75 80
Arg Thr Thr Ala Tyr Asn Val Trp Ala Val Thr Gly His Phe Ser Asn
85 90 95
Trp Leu Ala Thr Ser Leu Ser Ile Phe Tyr Leu Leu Lys Ile Ala Asn
100 105 110
Phe Ser Asn Leu Ile Phe Leu His Leu Lys Arg Arg Val Lys Ser Val
115 120 125
Ile Leu Val Met Leu Leu Gly Pro Leu Leu Phe Leu Ala Cys Gln Leu
130 135 140
Phe Val Ile Asn Met Lys Glu Ile Val Arg Thr Lys Glu Tyr Glu Gly
145 150 155 160
Asn Met Thr Trp Lys Ile Lys Leu Arg Ser Ala Val Tyr Leu Ser Asp
165 170 175
Ala Thr Val Thr Thr Leu Gly Asn Leu Val Pro Phe Thr Leu Thr Leu
180 185 190
Leu Cys Phe Leu Leu Leu Ile Cys Ser Leu Cys Lys His Leu Lys Lys
195 200 205
Met Gln Leu His Gly Lys Gly Ser Gln Asp Pro Ser Thr Lys Val His
210 215 220
Ile Lys Ala Leu Gln Thr Val Ile Phe Phe Leu Leu Leu Cys Ala Val
225 230 235 240
Tyr Phe Leu Ser Ile Met Ile Ser Val Trp Ser Phe Gly Ser Leu Glu
245 250 255
Asn Lys Pro Val Phe Met Phe Cys Lys Ala Ile Arg Phe Ser Tyr Pro
260 265 270
Ser Ile His Pro Phe Ile Leu Ile Trp Gly Asn Lys Lys Leu Lys Gln
275 280 285
Thr Phe Leu Ser Val Leu Arg Gln Val Arg Tyr Trp Val Lys Gly Glu
290 295 300
Lys Pro Ser Ser Pro
305
<210> 37
<211> 900
<212> DNA
<213> 智人
<220>
<221> CDS
<222> (1)..(900)
<400> 37
atg ata act ttt ctg ccc atc ata ttt tcc att cta gta gtg gtt aca 48
Met Ile Thr Phe Leu Pro Ile Ile Phe Ser Ile Leu Val Val Val Thr
1 5 10 15
ttt gtt att gga aat ttt gct aat ggc ttc ata gcg ttg gta aat tcc 96
Phe Val Ile Gly Asn Phe Ala Asn Gly Phe Ile Ala Leu Val Asn Ser
20 25 30
acc gag tgg gtg aag aga caa aag atc tcc ttt gct gac caa att gtc 144
Thr Glu Trp Val Lys Arg Gln Lys Ile Ser Phe Ala Asp Gln Ile Val
35 40 45
act gct ctg gcg gtc tcc aga gtt ggt ttg ctc tgg gtg tta tta tta 192
Thr Ala Leu Ala Val Ser Arg Val Gly Leu Leu Trp Val Leu Leu Leu
50 55 60
aat tgg tat tca act gtg ttg aat cca gct ttt tgt agt gta gaa tta 240
Asn Trp Tyr Ser Thr Val Leu Asn Pro Ala Phe Cys Ser Val Glu Leu
65 70 75 80
aga act act gct tat aat atc tgg gca gta acc ggc cat ttc agc aac 288
Arg Thr Thr Ala Tyr Asn Ile Trp Ala Val Thr Gly His Phe Ser Asn
85 90 95
tgg cct gct act agc ctc agc ata ttt tat ttg ctc aag att gcc aat 336
Trp Pro Ala Thr Ser Leu Ser Ile Phe Tyr Leu Leu Lys Ile Ala Asn
100 105 110
ttc tcc aac ctt att ttt ctt cgc tta aag agg aga gtt aag agt gtc 384
Phe Ser Asn Leu Ile Phe Leu Arg Leu Lys Arg Arg Val Lys Ser Val
115 120 125
att ctg gtg gtg ctg ttg ggg cct ttg cta ttt ttg gct tgt cat ctt 432
Ile Leu Val Val Leu Leu Gly Pro Leu Leu Phe Leu Ala Cys His Leu
130 135 140
ttt gtg gta aac atg aat cag att gta tgg aca aaa gaa tat gaa gga 480
Phe Val Val Asn Met Asn Gln Ile Val Trp Thr Lys Glu Tyr Glu Gly
145 150 155 160
aac atg act tgg aag atc aaa ttg agg cgt gca atg tac ctt tca gat 528
Asn Met Thr Trp Lys Ile Lys Leu Arg Arg Ala Met Tyr Leu Ser Asp
165 170 175
acg act gta acc atg cta gca aac tta gta ccc ttt act gta acc ctg 576
Thr Thr Val Thr Met Leu Ala Asn Leu Val Pro Phe Thr Val Thr Leu
180 185 190
ata tct ttt ctg ctg tta gtc tgt tct ctg tgt aaa cat ctc aag aag 624
Ile Ser Phe Leu Leu Leu Val Cys Ser Leu Cys Lys His Leu Lys Lys
195 200 205
atg cag ctc cat ggc aaa gga tct caa gat ccc agt acc aag gtc cac 672
Met Gln Leu His Gly Lys Gly Ser Gln Asp Pro Ser Thr Lys Val His
210 215 220
ata aaa gtt ttg caa act gtg atc tcc ttc ttc ttg tta cgt gcc att 720
Ile Lys Val Leu Gln Thr Val Ile Ser Phe Phe Leu Leu Arg Ala Ile
225 230 235 240
tac ttt gtg tct gta ata ata tca gtt tgg agt ttt aag aat ctg gaa 768
Tyr Phe Val Ser Val Ile Ile Ser Val Trp Ser Phe Lys Asn Leu Glu
245 250 255
aac aaa cct gtc ttc atg ttc tgc caa gct att gga ttc agc tgt tct 816
Asn Lys Pro Val Phe Met Phe Cys Gln Ala Ile Gly Phe Ser Cys Ser
260 265 270
tca gcc cac ccg ttc atc ctg att tgg gga aac aag aag cta aag cag 864
Ser Ala His Pro Phe Ile Leu Ile Trp Gly Asn Lys Lys Leu Lys Gln
275 280 285
act tat ctt tca gtt ttg tgg caa atg agg tac tga 900
Thr Tyr Leu Ser Val Leu Trp Gln Met Arg Tyr
290 295
<210> 38
<211> 299
<212> PRT
<213> 智人
<400> 38
Met Ile Thr Phe Leu Pro Ile Ile Phe Ser Ile Leu Val Val Val Thr
1 5 10 15
Phe Val Ile Gly Asn Phe Ala Asn Gly Phe Ile Ala Leu Val Asn Ser
20 25 30
Thr Glu Trp Val Lys Arg Gln Lys Ile Ser Phe Ala Asp Gln Ile Val
35 40 45
Thr Ala Leu Ala Val Ser Arg Val Gly Leu Leu Trp Val Leu Leu Leu
50 55 60
Asn Trp Tyr Ser Thr Val Leu Asn Pro Ala Phe Cys Ser Val Glu Leu
65 70 75 80
Arg Thr Thr Ala Tyr Asn Ile Trp Ala Val Thr Gly His Phe Ser Asn
85 90 95
Trp Pro Ala Thr Ser Leu Ser Ile Phe Tyr Leu Leu Lys Ile Ala Asn
100 105 110
Phe Ser Asn Leu Ile Phe Leu Arg Leu Lys Arg Arg Val Lys Ser Val
115 120 125
Ile Leu Val Val Leu Leu Gly Pro Leu Leu Phe Leu Ala Cys His Leu
130 135 140
Phe Val Val Asn Met Asn Gln Ile Val Trp Thr Lys Glu Tyr Glu Gly
145 150 155 160
Asn Met Thr Trp Lys Ile Lys Leu Arg Arg Ala Met Tyr Leu Ser Asp
165 170 175
Thr Thr Val Thr Met Leu Ala Asn Leu Val Pro Phe Thr Val Thr Leu
180 185 190
Ile Ser Phe Leu Leu Leu Val Cys Ser Leu Cys Lys His Leu Lys Lys
195 200 205
Met Gln Leu His Gly Lys Gly Ser Gln Asp Pro Ser Thr Lys Val His
210 215 220
Ile Lys Val Leu Gln Thr Val Ile Ser Phe Phe Leu Leu Arg Ala Ile
225 230 235 240
Tyr Phe Val Ser Val Ile Ile Ser Val Trp Ser Phe Lys Asn Leu Glu
245 250 255
Asn Lys Pro Val Phe Met Phe Cys Gln Ala Ile Gly Phe Ser Cys Ser
260 265 270
Ser Ala His Pro Phe Ile Leu Ile Trp Gly Asn Lys Lys Leu Lys Gln
275 280 285
Thr Tyr Leu Ser Val Leu Trp Gln Met Arg Tyr
290 295
<210> 39
<211> 930
<212> DNA
<213> 智人
<220>
<221> CDS
<222> (1)..(930)
<400> 39
atg ata act ttt ctg ccc atc att ttt tcc att cta ata gtg gtt aca 48
Met Ile Thr Phe Leu Pro Ile Ile Phe Ser Ile Leu Ile Val Val Thr
1 5 10 15
ttt gtg att gga aat ttt gct aat ggc ttc ata gca ttg gta aat tcc 96
Phe Val Ile Gly Asn Phe Ala Asn Gly Phe Ile Ala Leu Val Asn Ser
20 25 30
att gag tgg ttc aag aga caa aag atc tct ttt gct gac caa att ctc 144
Ile Glu Trp Phe Lys Arg Gln Lys Ile Ser Phe Ala Asp Gln Ile Leu
35 40 45
act gct ctg gca gtc tcc aga gtt ggt tta ctc tgg gta tta gta tta 192
Thr Ala Leu Ala Val Ser Arg Val Gly Leu Leu Trp Val Leu Val Leu
50 55 60
aat tgg tat gca act gag ttg aat cca gct ttt aac agt ata gaa gta 240
Asn Trp Tyr Ala Thr Glu Leu Asn Pro Ala Phe Asn Ser Ile Glu Val
65 70 75 80
aga att act gct tac aat gtc tgg gca gta atc aac cat ttc agc aac 288
Arg Ile Thr Ala Tyr Asn Val Trp Ala Val Ile Asn His Phe Ser Asn
85 90 95
tgg ctt gct act agc ctc agc ata ttt tat ttg ctc aag att gcc aat 336
Trp Leu Ala Thr Ser Leu Ser Ile Phe Tyr Leu Leu Lys Ile Ala Asn
100 105 110
ttc tcc aac ctt att ttt ctt cac tta aag agg aga gtt aag agt gtt 384
Phe Ser Asn Leu Ile Phe Leu His Leu Lys Arg Arg Val Lys Ser Val
115 120 125
gtt ctg gtg ata cta ttg ggg cct ttg cta ttt ttg gtt tgt cat ctt 432
Val Leu Val Ile Leu Leu Gly Pro Leu Leu Phe Leu Val Cys His Leu
130 135 140
ttt gtg ata aac atg aat cag att ata tgg aca aaa gaa tat gaa gga 480
Phe Val Ile Asn Met Asn Gln Ile Ile Trp Thr Lys Glu Tyr Glu Gly
145 150 155 160
aac atg act tgg aag atc aaa ctg agg agt gca atg tac ctt tca aat 528
Asn Met Thr Trp Lys Ile Lys Leu Arg Ser Ala Met Tyr Leu Ser Asn
165 170 175
aca acg gta acc atc cta gca aac tta gtt ccc ttc act ctg acc ctg 576
Thr Thr Val Thr Ile Leu Ala Asn Leu Val Pro Phe Thr Leu Thr Leu
180 185 190
ata tct ttt ctg ctg tta atc tgt tct ctg tgt aaa cat ctc aaa aag 624
Ile Ser Phe Leu Leu Leu Ile Cys Ser Leu Cys Lys His Leu Lys Lys
195 200 205
atg cag ctc cat ggc aaa gga tct caa gat ccc agc atg aag gtc cac 672
Met Gln Leu His Gly Lys Gly Ser Gln Asp Pro Ser Met Lys Val His
210 215 220
ata aaa gct ttg caa act gtg acc tcc ttc ctc ttg tta tgt gcc att 720
Ile Lys Ala Leu Gln Thr Val Thr Ser Phe Leu Leu Leu Cys Ala Ile
225 230 235 240
tac ttt ctg tcc ata atc atg tca gtt tgg agt ttt gag agt ctg gaa 768
Tyr Phe Leu Ser Ile Ile Met Ser Val Trp Ser Phe Glu Ser Leu Glu
245 250 255
aac aaa cct gtc ttc atg ttc tgc gaa gct att gca ttc agc tat cct 816
Asn Lys Pro Val Phe Met Phe Cys Glu Ala Ile Ala Phe Ser Tyr Pro
260 265 270
tca acc cac cca ttc atc ctg att tgg gga aac aag aag cta aag cag 864
Ser Thr His Pro Phe Ile Leu Ile Trp Gly Asn Lys Lys Leu Lys Gln
275 280 285
act ttt ctt tca gtt ttg tgg cat gtg agg tac tgg gtg aaa gga gag 912
Thr Phe Leu Ser Val Leu Trp His Val Arg Tyr Trp Val Lys Gly Glu
290 295 300
aag cct tca tct tca tag 930
Lys Pro Ser Ser Ser
305
<210> 40
<211> 309
<212> PRT
<213> 智人
<400> 40
Met Ile Thr Phe Leu Pro Ile Ile Phe Ser Ile Leu Ile Val Val Thr
1 5 10 15
Phe Val Ile Gly Asn Phe Ala Asn Gly Phe Ile Ala Leu Val Asn Ser
20 25 30
Ile Glu Trp Phe Lys Arg Gln Lys Ile Ser Phe Ala Asp Gln Ile Leu
35 40 45
Thr Ala Leu Ala Val Ser Arg Val Gly Leu Leu Trp Val Leu Val Leu
50 55 60
Asn Trp Tyr Ala Thr Glu Leu Asn Pro Ala Phe Asn Ser Ile Glu Val
65 70 75 80
Arg Ile Thr Ala Tyr Asn Val Trp Ala Val Ile Asn His Phe Ser Asn
85 90 95
Trp Leu Ala Thr Ser Leu Ser Ile Phe Tyr Leu Leu Lys Ile Ala Asn
100 105 110
Phe Ser Asn Leu Ile Phe Leu His Leu Lys Arg Arg Val Lys Ser Val
115 120 125
Val Leu Val Ile Leu Leu Gly Pro Leu Leu Phe Leu Val Cys His Leu
130 135 140
Phe Val Ile Asn Met Asn Gln Ile Ile Trp Thr Lys Glu Tyr Glu Gly
145 150 155 160
Asn Met Thr Trp Lys Ile Lys Leu Arg Ser Ala Met Tyr Leu Ser Asn
165 170 175
Thr Thr Val Thr Ile Leu Ala Asn Leu Val Pro Phe Thr Leu Thr Leu
180 185 190
Ile Ser Phe Leu Leu Leu Ile Cys Ser Leu Cys Lys His Leu Lys Lys
195 200 205
Met Gln Leu His Gly Lys Gly Ser Gln Asp Pro Ser Met Lys Val His
210 215 220
Ile Lys Ala Leu Gln Thr Val Thr Ser Phe Leu Leu Leu Cys Ala Ile
225 230 235 240
Tyr Phe Leu Ser Ile Ile Met Ser Val Trp Ser Phe Glu Ser Leu Glu
245 250 255
Asn Lys Pro Val Phe Met Phe Cys Glu Ala Ile Ala Phe Ser Tyr Pro
260 265 270
Ser Thr His Pro Phe Ile Leu Ile Trp Gly Asn Lys Lys Leu Lys Gln
275 280 285
Thr Phe Leu Ser Val Leu Trp His Val Arg Tyr Trp Val Lys Gly Glu
290 295 300
Lys Pro Ser Ser Ser
305
<210> 41
<211> 960
<212> DNA
<213> 智人
<220>
<221> CDS
<222> (1)..(960)
<400> 41
atg ata act ttt ctg ccc atc att ttt tcc att cta ata gtg gtt ata 48
Met Ile Thr Phe Leu Pro Ile Ile Phe Ser Ile Leu Ile Val Val Ile
1 5 10 15
ttt gtt att gga aat ttt gct aat ggc ttc ata gca ttg gta aat tcc 96
Phe Val Ile Gly Asn Phe Ala Asn Gly Phe Ile Ala Leu Val Asn Ser
20 25 30
att gag tgg gtc aag aga caa aag atc tcc ttt gtt gac caa att ctc 144
Ile Glu Trp Val Lys Arg Gln Lys Ile Ser Phe Val Asp Gln Ile Leu
35 40 45
act gct ctg gcg gtc tcc aga gtt ggt ttg ctc tgg gtg tta tta cta 192
Thr Ala Leu Ala Val Ser Arg Val Gly Leu Leu Trp Val Leu Leu Leu
50 55 60
cat tgg tat gca act cag ttg aat cca gct ttt tat agt gta gaa gta 240
His Trp Tyr Ala Thr Gln Leu Asn Pro Ala Phe Tyr Ser Val Glu Val
65 70 75 80
aga att act gct tat aat gtc tgg gca gta acc aac cat ttc agc agc 288
Arg Ile Thr Ala Tyr Asn Val Trp Ala Val Thr Asn His Phe Ser Ser
85 90 95
tgg ctt gct act agc ctc agc atg ttt tat ttg ctc agg att gcc aat 336
Trp Leu Ala Thr Ser Leu Ser Met Phe Tyr Leu Leu Arg Ile Ala Asn
100 105 110
ttc tcc aac ctt att ttt ctt cgc ata aag agg aga gtt aag agt gtt 384
Phe Ser Asn Leu Ile Phe Leu Arg Ile Lys Arg Arg Val Lys Ser Val
115 120 125
gtt ctg gtg ata ctg ttg ggg cct ttg cta ttt ttg gtt tgt cat ctt 432
Val Leu Val Ile Leu Leu Gly Pro Leu Leu Phe Leu Val Cys His Leu
130 135 140
ttt gtg ata aac atg gat gag act gta tgg aca aaa gaa tat gaa gga 480
Phe Val Ile Asn Met Asp Glu Thr Val Trp Thr Lys Glu Tyr Glu Gly
145 150 155 160
aac gtg act tgg aag atc aaa ttg agg agt gca atg tac cat tca aat 528
Asn Val Thr Trp Lys Ile Lys Leu Arg Ser Ala Met Tyr His Ser Asn
165 170 175
atg act cta acc atg cta gca aac ttt gta ccc ctc act ctg acc ctg 576
Met Thr Leu Thr Met Leu Ala Asn Phe Val Pro Leu Thr Leu Thr Leu
180 185 190
ata tct ttt ctg ctg tta atc tgt tct ctg tgt aaa cat ctc aag aag 624
Ile Ser Phe Leu Leu Leu Ile Cys Ser Leu Cys Lys His Leu Lys Lys
195 200 205
atg cag ctc cat ggc aaa gga tct caa gat ccc agc acc aag gtc cac 672
Met Gln Leu His Gly Lys Gly Ser Gln Asp Pro Ser Thr Lys Val His
210 215 220
ata aaa gct ttg caa act gtg acc tcc ttt ctt ctg tta tgt gcc att 720
Ile Lys Ala Leu Gln Thr Val Thr Ser Phe Leu Leu Leu Cys Ala Ile
225 230 235 240
tac ttt ctg tcc atg atc ata tca gtt tgt aat ttt ggg agg ctg gaa 768
Tyr Phe Leu Ser Met Ile Ile Ser Val Cys Asn Phe Gly Arg Leu Glu
245 250 255
aag caa cct gtc ttc atg ttc tgc caa gct att ata ttc agc tat cct 816
Lys Gln Pro Val Phe Met Phe Cys Gln Ala Ile Ile Phe Ser Tyr Pro
260 265 270
tca acc cac cca ttc atc ctg att ttg gga aac aag aag cta aag cag 864
Ser Thr His Pro Phe Ile Leu Ile Leu Gly Asn Lys Lys Leu Lys Gln
275 280 285
att ttt ctt tca gtt ttg cgg cat gtg agg tac tgg gtg aaa gac aga 912
Ile Phe Leu Ser Val Leu Arg His Val Arg Tyr Trp Val Lys Asp Arg
290 295 300
agc ctt cgt ctc cat aga ttc aca aga ggg gca ttg tgt gtc ttc tag 960
Ser Leu Arg Leu His Arg Phe Thr Arg Gly Ala Leu Cys Val Phe
305 310 315
<210> 42
<211> 319
<212> PRT
<213> 智人
<400> 42
Met Ile Thr Phe Leu Pro Ile Ile Phe Ser Ile Leu Ile Val Val Ile
1 5 10 15
Phe Val Ile Gly Asn Phe Ala Asn Gly Phe Ile Ala Leu Val Asn Ser
20 25 30
Ile Glu Trp Val Lys Arg Gln Lys Ile Ser Phe Val Asp Gln Ile Leu
35 40 45
Thr Ala Leu Ala Val Ser Arg Val Gly Leu Leu Trp Val Leu Leu Leu
50 55 60
His Trp Tyr Ala Thr Gln Leu Asn Pro Ala Phe Tyr Ser Val Glu Val
65 70 75 80
Arg Ile Thr Ala Tyr Asn Val Trp Ala Val Thr Asn His Phe Ser Ser
85 90 95
Trp Leu Ala Thr Ser Leu Ser Met Phe Tyr Leu Leu Arg Ile Ala Asn
100 105 110
Phe Ser Asn Leu Ile Phe Leu Arg Ile Lys Arg Arg Val Lys Ser Val
115 120 125
Val Leu Val Ile Leu Leu Gly Pro Leu Leu Phe Leu Val Cys His Leu
130 135 140
Phe Val Ile Asn Met Asp Glu Thr Val Trp Thr Lys Glu Tyr Glu Gly
145 150 155 160
Asn Val Thr Trp Lys Ile Lys Leu Arg Ser Ala Met Tyr His Ser Asn
165 170 175
Met Thr Leu Thr Met Leu Ala Asn Phe Val Pro Leu Thr Leu Thr Leu
180 185 190
Ile Ser Phe Leu Leu Leu Ile Cys Ser Leu Cys Lys His Leu Lys Lys
195 200 205
Met Gln Leu His Gly Lys Gly Ser Gln Asp Pro Ser Thr Lys Val His
210 215 220
Ile Lys Ala Leu Gln Thr Val Thr Ser Phe Leu Leu Leu Cys Ala Ile
225 230 235 240
Tyr Phe Leu Ser Met Ile Ile Ser Val Cys Asn Phe Gly Arg Leu Glu
245 250 255
Lys Gln Pro Val Phe Met Phe Cys Gln Ala Ile Ile Phe Ser Tyr Pro
260 265 270
Ser Thr His Pro Phe Ile Leu Ile Leu Gly Asn Lys Lys Leu Lys Gln
275 280 285
Ile Phe Leu Ser Val Leu Arg His Val Arg Tyr Trp Val Lys Asp Arg
290 295 300
Ser Leu Arg Leu His Arg Phe Thr Arg Gly Ala Leu Cys Val Phe
305 310 315
<210> 43
<211> 900
<212> DNA
<213> 智人
<220>
<221> CDS
<222> (1)..(900)
<400> 43
atg atg tgt ttt ctg ctc atc att tca tca att ctg gta gtg ttt gca 48
Met Met Cys Phe Leu Leu Ile Ile Ser Ser Ile Leu Val Val Phe Ala
1 5 10 15
ttt gtt ctt gga aat gtt gcc aat ggc ttc ata gcc cta gta aat gtc 96
Phe Val Leu Gly Asn Val Ala Asn Gly Phe Ile Ala Leu Val Asn Val
20 25 30
att gac tgg gtt aac aca cga aag atc tcc tca gct gag caa att ctc 144
Ile Asp Trp Val Asn Thr Arg Lys Ile Ser Ser Ala Glu Gln Ile Leu
35 40 45
act gct ctg gtg gtc tcc aga att ggt tta ctc tgg gtc atg tta ttc 192
Thr Ala Leu Val Val Ser Arg Ile Gly Leu Leu Trp Val Met Leu Phe
50 55 60
ctt tgg tat gca act gtg ttt aat tct gct tta tat ggt tta gaa gta 240
Leu Trp Tyr Ala Thr Val Phe Asn Ser Ala Leu Tyr Gly Leu Glu Val
65 70 75 80
aga att gtt gct tct aat gcc tgg gct gta acg aac cat ttc agc atg 288
Arg Ile Val Ala Ser Asn Ala Trp Ala Val Thr Asn His Phe Ser Met
85 90 95
tgg ctt gct gct agc ctc agc ata ttt tgt ttg ctc aag att gcc aat 336
Trp Leu Ala Ala Ser Leu Ser Ile Phe Cys Leu Leu Lys Ile Ala Asn
100 105 110
ttc tcc aac ctt att tct ctc cac cta aag aag aga att aag agt gtt 384
Phe Ser Asn Leu Ile Ser Leu His Leu Lys Lys Arg Ile Lys Ser Val
115 120 125
gtt ctg gtg ata ctg ttg ggg ccc ttg gta ttt ctg att tgt aat ctt 432
Val Leu Val Ile Leu Leu Gly Pro Leu Val Phe Leu Ile Cys Asn Leu
130 135 140
gct gtg ata acc atg gat gag aga gtg tgg aca aaa gaa tat gaa gga 480
Ala Val Ile Thr Met Asp Glu Arg Val Trp Thr Lys Glu Tyr Glu Gly
145 150 155 160
aat gtg act tgg aag atc aaa ttg agg aat gca ata cac ctt tca agc 528
Asn Val Thr Trp Lys Ile Lys Leu Arg Asn Ala Ile His Leu Ser Ser
165 170 175
ttg act gta act act cta gca aac ctc ata ccc ttt act ctg agc cta 576
Leu Thr Val Thr Thr Leu Ala Asn Leu Ile Pro Phe Thr Leu Ser Leu
180 185 190
ata tgt ttt ctg ctg tta atc tgt tct ctt tgt aaa cat ctc aag aag 624
Ile Cys Phe Leu Leu Leu Ile Cys Ser Leu Cys Lys His Leu Lys Lys
195 200 205
atg cgg ctc cat agc aaa gga tct caa gat ccc agc acc aag gtc cat 672
Met Arg Leu His Ser Lys Gly Ser Gln Asp Pro Ser Thr Lys Val His
210 215 220
ata aaa gct ttg caa act gtg acc tcc ttc ctc atg tta ttt gcc att 720
Ile Lys Ala Leu Gln Thr Val Thr Ser Phe Leu Met Leu Phe Ala Ile
225 230 235 240
tac ttt ctg tgt ata atc aca tca act tgg aat ctt agg aca cag cag 768
Tyr Phe Leu Cys Ile Ile Thr Ser Thr Trp Asn Leu Arg Thr Gln Gln
245 250 255
agc aaa ctt gta ctc ctg ctt tgc caa act gtt gca atc atg tat cct 816
Ser Lys Leu Val Leu Leu Leu Cys Gln Thr Val Ala Ile Met Tyr Pro
260 265 270
tca ttc cac tca ttc atc ctg att atg gga agt agg aag cta aaa cag 864
Ser Phe His Ser Phe Ile Leu Ile Met Gly Ser Arg Lys Leu Lys Gln
275 280 285
acc ttt ctt tca gtt ttg tgg cag atg aca cgc tga 900
Thr Phe Leu Ser Val Leu Trp Gln Met Thr Arg
290 295
<210> 44
<211> 299
<212> PRT
<213> 智人
<400> 44
Met Met Cys Phe Leu Leu Ile Ile Ser Ser Ile Leu Val Val Phe Ala
1 5 10 15
Phe Val Leu Gly Asn Val Ala Asn Gly Phe Ile Ala Leu Val Asn Val
20 25 30
Ile Asp Trp Val Asn Thr Arg Lys Ile Ser Ser Ala Glu Gln Ile Leu
35 40 45
Thr Ala Leu Val Val Ser Arg Ile Gly Leu Leu Trp Val Met Leu Phe
50 55 60
Leu Trp Tyr Ala Thr Val Phe Asn Ser Ala Leu Tyr Gly Leu Glu Val
65 70 75 80
Arg Ile Val Ala Ser Asn Ala Trp Ala Val Thr Asn His Phe Ser Met
85 90 95
Trp Leu Ala Ala Ser Leu Ser Ile Phe Cys Leu Leu Lys Ile Ala Asn
100 105 110
Phe Ser Asn Leu Ile Ser Leu His Leu Lys Lys Arg Ile Lys Ser Val
115 120 125
Val Leu Val Ile Leu Leu Gly Pro Leu Val Phe Leu Ile Cys Asn Leu
130 135 140
Ala Val Ile Thr Met Asp Glu Arg Val Trp Thr Lys Glu Tyr Glu Gly
145 150 155 160
Asn Val Thr Trp Lys Ile Lys Leu Arg Asn Ala Ile His Leu Ser Ser
165 170 175
Leu Thr Val Thr Thr Leu Ala Asn Leu Ile Pro Phe Thr Leu Ser Leu
180 185 190
Ile Cys Phe Leu Leu Leu Ile Cys Ser Leu Cys Lys His Leu Lys Lys
195 200 205
Met Arg Leu His Ser Lys Gly Ser Gln Asp Pro Ser Thr Lys Val His
210 215 220
Ile Lys Ala Leu Gln Thr Val Thr Ser Phe Leu Met Leu Phe Ala Ile
225 230 235 240
Tyr Phe Leu Cys Ile Ile Thr Ser Thr Trp Asn Leu Arg Thr Gln Gln
245 250 255
Ser Lys Leu Val Leu Leu Leu Cys Gln Thr Val Ala Ile Met Tyr Pro
260 265 270
Ser Phe His Ser Phe Ile Leu Ile Met Gly Ser Arg Lys Leu Lys Gln
275 280 285
Thr Phe Leu Ser Val Leu Trp Gln Met Thr Arg
290 295
<210> 45
<211> 930
<212> DNA
<213> 智人
<220>
<221> CDS
<222> (1)..(930)
<400> 45
atg atg agt ttt cta cac att gtt ttt tcc att cta gta gtg gtt gca 48
Met Met Ser Phe Leu His Ile Val Phe Ser Ile Leu Val Val Val Ala
1 5 10 15
ttt att ctt gga aat ttt gcc aat ggc ttt ata gca ctg ata aat ttc 96
Phe Ile Leu Gly Asn Phe Ala Asn Gly Phe Ile Ala Leu Ile Asn Phe
20 25 30
att gcc tgg gtc aag aga caa aag atc tcc tca gct gat caa att att 144
Ile Ala Trp Val Lys Arg Gln Lys Ile Ser Ser Ala Asp Gln Ile Ile
35 40 45
gct gct ctg gca gtc tcc aga gtt ggt ttg ctc tgg gta ata tta tta 192
Ala Ala Leu Ala Val Ser Arg Val Gly Leu Leu Trp Val Ile Leu Leu
50 55 60
cat tgg tat tca act gtg ttg aat cca act tca tct aat tta aaa gta 240
His Trp Tyr Ser Thr Val Leu Asn Pro Thr Ser Ser Asn Leu Lys Val
65 70 75 80
ata att ttt att tct aat gcc tgg gca gta acc aat cat ttc agc atc 288
Ile Ile Phe Ile Ser Asn Ala Trp Ala Val Thr Asn His Phe Ser Ile
85 90 95
tgg ctt gct act agc ctc agc ata ttt tat ttg ctc aag atc gtc aat 336
Trp Leu Ala Thr Ser Leu Ser Ile Phe Tyr Leu Leu Lys Ile Val Asn
100 105 110
ttc tcc aga ctt att ttt cat cac tta aaa agg aag gct aag agt gta 384
Phe Ser Arg Leu Ile Phe His His Leu Lys Arg Lys Ala Lys Ser Val
115 120 125
gtt ctg gtg ata gtg ttg ggg tct ttg ttc ttt ttg gtt tgt cac ctt 432
Val Leu Val Ile Val Leu Gly Ser Leu Phe Phe Leu Val Cys His Leu
130 135 140
gtg atg aaa cac acg tat ata aat gtg tgg aca gaa gaa tgt gaa gga 480
Val Met Lys His Thr Tyr Ile Asn Val Trp Thr Glu Glu Cys Glu Gly
145 150 155 160
aac gta act tgg aag atc aaa ctg agg aat gca atg cac ctt tcc aac 528
Asn Val Thr Trp Lys Ile Lys Leu Arg Asn Ala Met His Leu Ser Asn
165 170 175
ttg act gta gcc atg cta gca aac ttg ata cca ttc act ctg acc ctg 576
Leu Thr Val Ala Met Leu Ala Asn Leu Ile Pro Phe Thr Leu Thr Leu
180 185 190
ata tct ttt ctg ctg tta atc tac tct ctg tgt aaa cat ctg aag aag 624
Ile Ser Phe Leu Leu Leu Ile Tyr Ser Leu Cys Lys His Leu Lys Lys
195 200 205
atg cag ctc cat ggc aaa gga tct caa gat ccc agc acc aag atc cac 672
Met Gln Leu His Gly Lys Gly Ser Gln Asp Pro Ser Thr Lys Ile His
210 215 220
ata aaa gct ctg caa act gtg acc tcc ttc ctc ata tta ctt gcc att 720
Ile Lys Ala Leu Gln Thr Val Thr Ser Phe Leu Ile Leu Leu Ala Ile
225 230 235 240
tac ttt ctg tgt cta atc ata tcg ttt tgg aat ttt aag atg cga cca 768
Tyr Phe Leu Cys Leu Ile Ile Ser Phe Trp Asn Phe Lys Met Arg Pro
245 250 255
aaa gaa att gtc tta atg ctt tgc caa gct ttt gga atc ata tat cca 816
Lys Glu Ile Val Leu Met Leu Cys Gln Ala Phe Gly Ile Ile Tyr Pro
260 265 270
tca ttc cac tca ttc att ctg att tgg ggg aac aag acg cta aag cag 864
Ser Phe His Ser Phe Ile Leu Ile Trp Gly Asn Lys Thr Leu Lys Gln
275 280 285
acc ttt ctt tca gtt ttg tgg cag gtg act tgc tgg gca aaa gga cag 912
Thr Phe Leu Ser Val Leu Trp Gln Val Thr Cys Trp Ala Lys Gly Gln
290 295 300
aac cag tca act cca tag 930
Asn Gln Ser Thr Pro
305
<210> 46
<211> 309
<212> PRT
<213> 智人
<400> 46
Met Met Ser Phe Leu His Ile Val Phe Ser Ile Leu Val Val Val Ala
1 5 10 15
Phe Ile Leu Gly Asn Phe Ala Asn Gly Phe Ile Ala Leu Ile Asn Phe
20 25 30
Ile Ala Trp Val Lys Arg Gln Lys Ile Ser Ser Ala Asp Gln Ile Ile
35 40 45
Ala Ala Leu Ala Val Ser Arg Val Gly Leu Leu Trp Val Ile Leu Leu
50 55 60
His Trp Tyr Ser Thr Val Leu Asn Pro Thr Ser Ser Asn Leu Lys Val
65 70 75 80
Ile Ile Phe Ile Ser Asn Ala Trp Ala Val Thr Asn His Phe Ser Ile
85 90 95
Trp Leu Ala Thr Ser Leu Ser Ile Phe Tyr Leu Leu Lys Ile Val Asn
100 105 110
Phe Ser Arg Leu Ile Phe His His Leu Lys Arg Lys Ala Lys Ser Val
115 120 125
Val Leu Val Ile Val Leu Gly Ser Leu Phe Phe Leu Val Cys His Leu
130 135 140
Val Met Lys His Thr Tyr Ile Asn Val Trp Thr Glu Glu Cys Glu Gly
145 150 155 160
Asn Val Thr Trp Lys Ile Lys Leu Arg Asn Ala Met His Leu Ser Asn
165 170 175
Leu Thr Val Ala Met Leu Ala Asn Leu Ile Pro Phe Thr Leu Thr Leu
180 185 190
Ile Ser Phe Leu Leu Leu Ile Tyr Ser Leu Cys Lys His Leu Lys Lys
195 200 205
Met Gln Leu His Gly Lys Gly Ser Gln Asp Pro Ser Thr Lys Ile His
210 215 220
Ile Lys Ala Leu Gln Thr Val Thr Ser Phe Leu Ile Leu Leu Ala Ile
225 230 235 240
Tyr Phe Leu Cys Leu Ile Ile Ser Phe Trp Asn Phe Lys Met Arg Pro
245 250 255
Lys Glu Ile Val Leu Met Leu Cys Gln Ala Phe Gly Ile Ile Tyr Pro
260 265 270
Ser Phe His Ser Phe Ile Leu Ile Trp Gly Asn Lys Thr Leu Lys Gln
275 280 285
Thr Phe Leu Ser Val Leu Trp Gln Val Thr Cys Trp Ala Lys Gly Gln
290 295 300
Asn Gln Ser Thr Pro
305
<210> 47
<211> 900
<212> DNA
<213> 智人
<220>
<221> CDS
<222> (1)..(900)
<400> 47
atg ata act ttt cta tac att ttt ttt tca att cta ata atg gtt tta 48
Met Ile Thr Phe Leu Tyr Ile Phe Phe Ser Ile Leu Ile Met Val Leu
1 5 10 15
ttt gtt ctc gga aac ttt gcc aat ggc ttc ata gca ctg gta aat ttc 96
Phe Val Leu Gly Asn Phe Ala Asn Gly Phe Ile Ala Leu Val Asn Phe
20 25 30
att gac tgg gtg aag aga aaa aag atc tcc tca gct gac caa att ctc 144
Ile Asp Trp Val Lys Arg Lys Lys Ile Ser Ser Ala Asp Gln Ile Leu
35 40 45
act gct ctg gcg gtc tcc aga att ggt ttg ctc tgg gca tta tta tta 192
Thr Ala Leu Ala Val Ser Arg Ile Gly Leu Leu Trp Ala Leu Leu Leu
50 55 60
aat tgg tat tta act gtg ttg aat cca gct ttt tat agt gta gaa tta 240
Asn Trp Tyr Leu Thr Val Leu Asn Pro Ala Phe Tyr Ser Val Glu Leu
65 70 75 80
aga att act tct tat aat gcc tgg gtt gta acc aac cat ttc agc atg 288
Arg Ile Thr Ser Tyr Asn Ala Trp Val Val Thr Asn His Phe Ser Met
85 90 95
tgg ctt gct gct aac ctc agc ata ttt tat ttg ctc aag att gcc aat 336
Trp Leu Ala Ala Asn Leu Ser Ile Phe Tyr Leu Leu Lys Ile Ala Asn
100 105 110
ttc tcc aac ctt ctt ttt ctt cat tta aag agg aga gtt agg agt gtc 384
Phe Ser Asn Leu Leu Phe Leu His Leu Lys Arg Arg Val Arg Ser Val
115 120 125
att ctg gtg ata ctg ttg ggg act ttg ata ttt ttg gtt tgt cat ctt 432
Ile Leu Val Ile Leu Leu Gly Thr Leu Ile Phe Leu Val Cys His Leu
130 135 140
ctt gtg gca aac atg gat gag agt atg tgg gca gaa gaa tat gaa gga 480
Leu Val Ala Asn Met Asp Glu Ser Met Trp Ala Glu Glu Tyr Glu Gly
145 150 155 160
aac atg act ggg aag atg aaa ttg agg aat aca gta cat ctt tca tat 528
Asn Met Thr Gly Lys Met Lys Leu Arg Asn Thr Val His Leu Ser Tyr
165 170 175
ttg act gta act acc cta tgg agc ttc ata ccc ttt act ctg tcc ctg 576
Leu Thr Val Thr Thr Leu Trp Ser Phe Ile Pro Phe Thr Leu Ser Leu
180 185 190
ata tct ttt ctg atg cta atc tgt tct ctg tgt aaa cat ctc aag aag 624
Ile Ser Phe Leu Met Leu Ile Cys Ser Leu Cys Lys His Leu Lys Lys
195 200 205
atg cag ctc cat gga gaa gga tcg caa gat ctc agc acc aag gtc cac 672
Met Gln Leu His Gly Glu Gly Ser Gln Asp Leu Ser Thr Lys Val His
210 215 220
ata aaa gct ttg caa act ctg atc tcc ttc ctc ttg tta tgt gcc att 720
Ile Lys Ala Leu Gln Thr Leu Ile Ser Phe Leu Leu Leu Cys Ala Ile
225 230 235 240
ttc ttt cta ttc cta atc gtt tcg gtt tgg agt cct agg agg ctg cgg 768
Phe Phe Leu Phe Leu Ile Val Ser Val Trp Ser Pro Arg Arg Leu Arg
245 250 255
aat gac ccg gtt gtc atg gtt agc aag gct gtt gga aac ata tat ctt 816
Asn Asp Pro Val Val Met Val Ser Lys Ala Val Gly Asn Ile Tyr Leu
260 265 270
gca ttc gac tca ttc atc cta att tgg aga acc aag aag cta aaa cac 864
Ala Phe Asp Ser Phe Ile Leu Ile Trp Arg Thr Lys Lys Leu Lys His
275 280 285
acc ttt ctt ttg att ttg tgt cag att agg tgc tga 900
Thr Phe Leu Leu Ile Leu Cys Gln Ile Arg Cys
290 295
<210> 48
<211> 299
<212> PRT
<213> 智人
<400> 48
Met Ile Thr Phe Leu Tyr Ile Phe Phe Ser Ile Leu Ile Met Val Leu
1 5 10 15
Phe Val Leu Gly Asn Phe Ala Asn Gly Phe Ile Ala Leu Val Asn Phe
20 25 30
Ile Asp Trp Val Lys Arg Lys Lys Ile Ser Ser Ala Asp Gln Ile Leu
35 40 45
Thr Ala Leu Ala Val Ser Arg Ile Gly Leu Leu Trp Ala Leu Leu Leu
50 55 60
Asn Trp Tyr Leu Thr Val Leu Asn Pro Ala Phe Tyr Ser Val Glu Leu
65 70 75 80
Arg Ile Thr Ser Tyr Asn Ala Trp Val Val Thr Asn His Phe Ser Met
85 90 95
Trp Leu Ala Ala Asn Leu Ser Ile Phe Tyr Leu Leu Lys Ile Ala Asn
100 105 110
Phe Ser Asn Leu Leu Phe Leu His Leu Lys Arg Arg Val Arg Ser Val
115 120 125
Ile Leu Val Ile Leu Leu Gly Thr Leu Ile Phe Leu Val Cys His Leu
130 135 140
Leu Val Ala Asn Met Asp Glu Ser Met Trp Ala Glu Glu Tyr Glu Gly
145 150 155 160
Asn Met Thr Gly Lys Met Lys Leu Arg Asn Thr Val His Leu Ser Tyr
165 170 175
Leu Thr Val Thr Thr Leu Trp Ser Phe Ile Pro Phe Thr Leu Ser Leu
180 185 190
Ile Ser Phe Leu Met Leu Ile Cys Ser Leu Cys Lys His Leu Lys Lys
195 200 205
Met Gln Leu His Gly Glu Gly Ser Gln Asp Leu Ser Thr Lys Val His
210 215 220
Ile Lys Ala Leu Gln Thr Leu Ile Ser Phe Leu Leu Leu Cys Ala Ile
225 230 235 240
Phe Phe Leu Phe Leu Ile Val Ser Val Trp Ser Pro Arg Arg Leu Arg
245 250 255
Asn Asp Pro Val Val Met Val Ser Lys Ala Val Gly Asn Ile Tyr Leu
260 265 270
Ala Phe Asp Ser Phe Ile Leu Ile Trp Arg Thr Lys Lys Leu Lys His
275 280 285
Thr Phe Leu Leu Ile Leu Cys Gln Ile Arg Cys
290 295
<210> 49
<211> 957
<212> DNA
<213> 智人
<220>
<221> CDS
<222> (1)..(957)
<400> 49
atg aat gga gac cac atg gtt cta gga tct tcg gtg act gac aag aag 48
Met Asn Gly Asp His Met Val Leu Gly Ser Ser Val Thr Asp Lys Lys
1 5 10 15
gcc atc atc ttg gtt acc att tta ctc ctt tta cgc ctg gta gca ata 96
Ala Ile Ile Leu Val Thr Ile Leu Leu Leu Leu Arg Leu Val Ala Ile
20 25 30
gca ggc aat ggc ttc atc act gct gct ctg ggc gtg gag tgg gtg cta 144
Ala Gly Asn Gly Phe Ile Thr Ala Ala Leu Gly Val Glu Trp Val Leu
35 40 45
cgg aga atg ttg ttg cct tgt gat aag tta ttg gtt agc cta ggg gcc 192
Arg Arg Met Leu Leu Pro Cys Asp Lys Leu Leu Val Ser Leu Gly Ala
50 55 60
tct cgc ttc tgt ctg cag tca gtg gta atg ggt aag acc att tat gtt 240
Ser Arg Phe Cys Leu Gln Ser Val Val Met Gly Lys Thr Ile Tyr Val
65 70 75 80
ttc ttg cat ccg atg gcc ttc cca tac aac cct gta ctg cag ttt cta 288
Phe Leu His Pro Met Ala Phe Pro Tyr Asn Pro Val Leu Gln Phe Leu
85 90 95
gct ttc cag tgg gac ttc ctg aat gct gcc acc tta tgg tcc tct acc 336
Ala Phe Gln Trp Asp Phe Leu Asn Ala Ala Thr Leu Trp Ser Ser Thr
100 105 110
tgg ctc agt gtc ttc tat tgt gtg aaa att gct acc ttc acc cac cct 384
Trp Leu Ser Val Phe Tyr Cys Val Lys Ile Ala Thr Phe Thr His Pro
115 120 125
gtc ttc ttc tgg cta aag cac aag ttg tct ggg tgg cta cca tgg atg 432
Val Phe Phe Trp Leu Lys His Lys Leu Ser Gly Trp Leu Pro Trp Met
130 135 140
ctc ttc agc tct gta ggg ctc tcc agc ttc acc acc att cta ttt ttc 480
Leu Phe Ser Ser Val Gly Leu Ser Ser Phe Thr Thr Ile Leu Phe Phe
145 150 155 160
ata ggc aac cac aga atg tat cag aac tat tta agg aac cat cta caa 528
Ile Gly Asn His Arg Met Tyr Gln Asn Tyr Leu Arg Asn His Leu Gln
165 170 175
cct tgg aat gtc act ggc gat agc ata cgg agc tac tgt gag aaa ttc 576
Pro Trp Asn Val Thr Gly Asp Ser Ile Arg Ser Tyr Cys Glu Lys Phe
180 185 190
tat ctc ttc cct cta aaa atg att act tgg aca atg ccc act gct gtc 624
Tyr Leu Phe Pro Leu Lys Met Ile Thr Trp Thr Met Pro Thr Ala Val
195 200 205
ttt ttc att tgc atg att ttg ctc atc aca tct ctg gga aga cac agg 672
Phe Phe Ile Cys Met Ile Leu Leu Ile Thr Ser Leu Gly Arg His Arg
210 215 220
aag aag gct ctc ctt aca acc tca gga ttc cga gag ccc agt gtg cag 720
Lys Lys Ala Leu Leu Thr Thr Ser Gly Phe Arg Glu Pro Ser Val Gln
225 230 235 240
gca cac ata aag gct ctg ctg gct ctc ctc tct ttt gcc atg ctc ttc 768
Ala His Ile Lys Ala Leu Leu Ala Leu Leu Ser Phe Ala Met Leu Phe
245 250 255
atc tca tat ttc ctg tca ctg gtg ttc agt gct gca ggt att ttt cca 816
Ile Ser Tyr Phe Leu Ser Leu Val Phe Ser Ala Ala Gly Ile Phe Pro
260 265 270
cct ctg gac ttt aaa ttc tgg gtg tgg gag tca gtg att tat ctg tgt 864
Pro Leu Asp Phe Lys Phe Trp Val Trp Glu Ser Val Ile Tyr Leu Cys
275 280 285
gca gca gtt cac ccc atc att ctg ctc ttc agc aac tgc agg ctg aga 912
Ala Ala Val His Pro Ile Ile Leu Leu Phe Ser Asn Cys Arg Leu Arg
290 295 300
gct gtg ctg aag agt cgt cgt tcc tca agg tgt ggg aca cct tga 957
Ala Val Leu Lys Ser Arg Arg Ser Ser Arg Cys Gly Thr Pro
305 310 315
<210> 50
<211> 318
<212> PRT
<213> 智人
<400> 50
Met Asn Gly Asp His Met Val Leu Gly Ser Ser Val Thr Asp Lys Lys
1 5 10 15
Ala Ile Ile Leu Val Thr Ile Leu Leu Leu Leu Arg Leu Val Ala Ile
20 25 30
Ala Gly Asn Gly Phe Ile Thr Ala Ala Leu Gly Val Glu Trp Val Leu
35 40 45
Arg Arg Met Leu Leu Pro Cys Asp Lys Leu Leu Val Ser Leu Gly Ala
50 55 60
Ser Arg Phe Cys Leu Gln Ser Val Val Met Gly Lys Thr Ile Tyr Val
65 70 75 80
Phe Leu His Pro Met Ala Phe Pro Tyr Asn Pro Val Leu Gln Phe Leu
85 90 95
Ala Phe Gln Trp Asp Phe Leu Asn Ala Ala Thr Leu Trp Ser Ser Thr
100 105 110
Trp Leu Ser Val Phe Tyr Cys Val Lys Ile Ala Thr Phe Thr His Pro
115 120 125
Val Phe Phe Trp Leu Lys His Lys Leu Ser Gly Trp Leu Pro Trp Met
130 135 140
Leu Phe Ser Ser Val Gly Leu Ser Ser Phe Thr Thr Ile Leu Phe Phe
145 150 155 160
Ile Gly Asn His Arg Met Tyr Gln Asn Tyr Leu Arg Asn His Leu Gln
165 170 175
Pro Trp Asn Val Thr Gly Asp Ser Ile Arg Ser Tyr Cys Glu Lys Phe
180 185 190
Tyr Leu Phe Pro Leu Lys Met Ile Thr Trp Thr Met Pro Thr Ala Val
195 200 205
Phe Phe Ile Cys Met Ile Leu Leu Ile Thr Ser Leu Gly Arg His Arg
210 215 220
Lys Lys Ala Leu Leu Thr Thr Ser Gly Phe Arg Glu Pro Ser Val Gln
225 230 235 240
Ala His Ile Lys Ala Leu Leu Ala Leu Leu Ser Phe Ala Met Leu Phe
245 250 255
Ile Ser Tyr Phe Leu Ser Leu Val Phe Ser Ala Ala Gly Ile Phe Pro
260 265 270
Pro Leu Asp Phe Lys Phe Trp Val Trp Glu Ser Val Ile Tyr Leu Cys
275 280 285
Ala Ala Val His Pro Ile Ile Leu Leu Phe Ser Asn Cys Arg Leu Arg
290 295 300
Ala Val Leu Lys Ser Arg Arg Ser Ser Arg Cys Gly Thr Pro
305 310 315
<210> 51
<211> 948
<212> DNA
<213> 智人
<220>
<221> CDS
<222> (1)..(948)
<400> 51
atg cag cca gaa tct ggg gcc aat gga aca gtc att gct gag ttc atc 48
Met Gln Pro Glu Ser Gly Ala Asn Gly Thr Val Ile Ala Glu Phe Ile
1 5 10 15
ctg ctg ggc ttg ctg gag gcg cca ggg ctg cag cca gtt gtc ttt gtg 96
Leu Leu Gly Leu Leu Glu Ala Pro Gly Leu Gln Pro Val Val Phe Val
20 25 30
ctc ttc ctc ttt gcc tac ctg gtc acg gtc agg ggc aac ctc agc atc 144
Leu Phe Leu Phe Ala Tyr Leu Val Thr Val Arg Gly Asn Leu Ser Ile
35 40 45
ctg gca gct gtc ttg gtg gag ccc aaa ctc cac acc ccc atg tac ttc 192
Leu Ala Ala Val Leu Val Glu Pro Lys Leu His Thr Pro Met Tyr Phe
50 55 60
ttc ctg ggg aac cta tca gtg ctg gat gtt ggg tgc atc agc gtc act 240
Phe Leu Gly Asn Leu Ser Val Leu Asp Val Gly Cys Ile Ser Val Thr
65 70 75 80
gtt cca tca atg ttg agt cgt ctc ctg tcc cgc aag cgt gca gtt ccc 288
Val Pro Ser Met Leu Ser Arg Leu Leu Ser Arg Lys Arg Ala Val Pro
85 90 95
tgt ggg gcc tgc ctt acc cag ctc ttc ttc ttc cat ctg ttc gtt gga 336
Cys Gly Ala Cys Leu Thr Gln Leu Phe Phe Phe His Leu Phe Val Gly
100 105 110
gtg gac tgc ttc ctg ctg acc gcc atg gcc tat gac cga ttc ctg gcc 384
Val Asp Cys Phe Leu Leu Thr Ala Met Ala Tyr Asp Arg Phe Leu Ala
115 120 125
atc tgc cgg ccc ctc acc tac agc acc cgc atg agt cag aca gtc cag 432
Ile Cys Arg Pro Leu Thr Tyr Ser Thr Arg Met Ser Gln Thr Val Gln
130 135 140
agg atg ttg gtg gct gcg tcc tgg gct tgt gct ttc acc aac gca ctg 480
Arg Met Leu Val Ala Ala Ser Trp Ala Cys Ala Phe Thr Asn Ala Leu
145 150 155 160
acc cac act gtg gcc atg tcc acg ctc aac ttc tgt ggc ccc aat gtg 528
Thr His Thr Val Ala Met Ser Thr Leu Asn Phe Cys Gly Pro Asn Val
165 170 175
atc aat cac ttc tac tgt gac ctc cca cag ctc ttc cag ctc tcc tgc 576
Ile Asn His Phe Tyr Cys Asp Leu Pro Gln Leu Phe Gln Leu Ser Cys
180 185 190
tcc agc acc caa ctc aat gag ctg ctg ctt ttt gct gtg ggt ttt ata 624
Ser Ser Thr Gln Leu Asn Glu Leu Leu Leu Phe Ala Val Gly Phe Ile
195 200 205
atg gca ggt acc ccc atg gct ctc att gtc atc tcc tat atc cac gtg 672
Met Ala Gly Thr Pro Met Ala Leu Ile Val Ile Ser Tyr Ile His Val
210 215 220
gca gct gca gtc ctg cga att cgc tct gta gag ggc agg aag aaa gcc 720
Ala Ala Ala Val Leu Arg Ile Arg Ser Val Glu Gly Arg Lys Lys Ala
225 230 235 240
ttc tcc aca tgt ggc tcc cac ctc act gtg gtt gcc ata ttc tat ggt 768
Phe Ser Thr Cys Gly Ser His Leu Thr Val Val Ala Ile Phe Tyr Gly
245 250 255
tca ggt atc ttt aac tat atg cga ctg ggt tca acc aag ctt tca gac 816
Ser Gly Ile Phe Asn Tyr Met Arg Leu Gly Ser Thr Lys Leu Ser Asp
260 265 270
aag gat aaa gct gtt gga att ttc aac act gtc atc aat ccc atg ctg 864
Lys Asp Lys Ala Val Gly Ile Phe Asn Thr Val Ile Asn Pro Met Leu
275 280 285
aac cca atc atc tac agc ttc aga aac cct gat gtg cag agt gcc atc 912
Asn Pro Ile Ile Tyr Ser Phe Arg Asn Pro Asp Val Gln Ser Ala Ile
290 295 300
tgg agg atg ctc aca ggg agg cgg tca ctg gct tga 948
Trp Arg Met Leu Thr Gly Arg Arg Ser Leu Ala
305 310 315
<210> 52
<211> 315
<212> PRT
<213> 智人
<400> 52
Met Gln Pro Glu Ser Gly Ala Asn Gly Thr Val Ile Ala Glu Phe Ile
1 5 10 15
Leu Leu Gly Leu Leu Glu Ala Pro Gly Leu Gln Pro Val Val Phe Val
20 25 30
Leu Phe Leu Phe Ala Tyr Leu Val Thr Val Arg Gly Asn Leu Ser Ile
35 40 45
Leu Ala Ala Val Leu Val Glu Pro Lys Leu His Thr Pro Met Tyr Phe
50 55 60
Phe Leu Gly Asn Leu Ser Val Leu Asp Val Gly Cys Ile Ser Val Thr
65 70 75 80
Val Pro Ser Met Leu Ser Arg Leu Leu Ser Arg Lys Arg Ala Val Pro
85 90 95
Cys Gly Ala Cys Leu Thr Gln Leu Phe Phe Phe His Leu Phe Val Gly
100 105 110
Val Asp Cys Phe Leu Leu Thr Ala Met Ala Tyr Asp Arg Phe Leu Ala
115 120 125
Ile Cys Arg Pro Leu Thr Tyr Ser Thr Arg Met Ser Gln Thr Val Gln
130 135 140
Arg Met Leu Val Ala Ala Ser Trp Ala Cys Ala Phe Thr Asn Ala Leu
145 150 155 160
Thr His Thr Val Ala Met Ser Thr Leu Asn Phe Cys Gly Pro Asn Val
165 170 175
Ile Asn His Phe Tyr Cys Asp Leu Pro Gln Leu Phe Gln Leu Ser Cys
180 185 190
Ser Ser Thr Gln Leu Asn Glu Leu Leu Leu Phe Ala Val Gly Phe Ile
195 200 205
Met Ala Gly Thr Pro Met Ala Leu Ile Val Ile Ser Tyr Ile His Val
210 215 220
Ala Ala Ala Val Leu Arg Ile Arg Ser Val Glu Gly Arg Lys Lys Ala
225 230 235 240
Phe Ser Thr Cys Gly Ser His Leu Thr Val Val Ala Ile Phe Tyr Gly
245 250 255
Ser Gly Ile Phe Asn Tyr Met Arg Leu Gly Ser Thr Lys Leu Ser Asp
260 265 270
Lys Asp Lys Ala Val Gly Ile Phe Asn Thr Val Ile Asn Pro Met Leu
275 280 285
Asn Pro Ile Ile Tyr Ser Phe Arg Asn Pro Asp Val Gln Ser Ala Ile
290 295 300
Trp Arg Met Leu Thr Gly Arg Arg Ser Leu Ala
305 310 315
<210> 53
<211> 939
<212> DNA
<213> 智人
<220>
<221> CDS
<222> (1)..(939)
<400> 53
atg gat gga ggc aac cag agt gaa ggt tca gag ttc ctt ctc ctg ggg 48
Met Asp Gly Gly Asn Gln Ser Glu Gly Ser Glu Phe Leu Leu Leu Gly
1 5 10 15
atg tca gag agt cct gag cag cag cgg atc ctg ttt tgg atg ttc ctg 96
Met Ser Glu Ser Pro Glu Gln Gln Arg Ile Leu Phe Trp Met Phe Leu
20 25 30
tcc atg tac ctg gtc acg gtg gtg gga aat gtg ctc atc atc ctg gcc 144
Ser Met Tyr Leu Val Thr Val Val Gly Asn Val Leu Ile Ile Leu Ala
35 40 45
atc agc tct gat tcc cgc ctg cac acc ccc gtg tac ttc ttc ctg gcc 192
Ile Ser Ser Asp Ser Arg Leu His Thr Pro Val Tyr Phe Phe Leu Ala
50 55 60
aac ctc tcc ttc act gac ctc ttc ttt gtc acc aac aca atc ccc aag 240
Asn Leu Ser Phe Thr Asp Leu Phe Phe Val Thr Asn Thr Ile Pro Lys
65 70 75 80
atg ctg gtg aac ctc cag tcc cat aac aaa gcc atc tcc tat gca ggg 288
Met Leu Val Asn Leu Gln Ser His Asn Lys Ala Ile Ser Tyr Ala Gly
85 90 95
tgt ctg aca cag ctc tac ttc ctg gtc tcc ttg gtg gcc ctg gac aac 336
Cys Leu Thr Gln Leu Tyr Phe Leu Val Ser Leu Val Ala Leu Asp Asn
100 105 110
ctc atc ctg gct gtg atg gca tat gac cgc tat gtg gcc atc tgc tgc 384
Leu Ile Leu Ala Val Met Ala Tyr Asp Arg Tyr Val Ala Ile Cys Cys
115 120 125
ccc ctc cac tac acc aca gcc atg agc cct aag ctc tgt atc tta ctc 432
Pro Leu His Tyr Thr Thr Ala Met Ser Pro Lys Leu Cys Ile Leu Leu
130 135 140
ctt tcc ttg tgt tgg gtc cta tcc gtc ctc tat ggc ctc ata cac acc 480
Leu Ser Leu Cys Trp Val Leu Ser Val Leu Tyr Gly Leu Ile His Thr
145 150 155 160
ctc ctc atg acc aga gtg acc ttc tgt ggg tca cga aaa atc cac tac 528
Leu Leu Met Thr Arg Val Thr Phe Cys Gly Ser Arg Lys Ile His Tyr
165 170 175
atc ttc tgt gag atg tat gta ttg ctg agg atg gca tgt tcc aac att 576
Ile Phe Cys Glu Met Tyr Val Leu Leu Arg Met Ala Cys Ser Asn Ile
180 185 190
cag att aat cac aca gtg ctg att gcc aca ggc tgc ttc atc ttc ctc 624
Gln Ile Asn His Thr Val Leu Ile Ala Thr Gly Cys Phe Ile Phe Leu
195 200 205
att ccc ttt gga ttc gtg atc att tcc tat gtg ctg att atc aga gcc 672
Ile Pro Phe Gly Phe Val Ile Ile Ser Tyr Val Leu Ile Ile Arg Ala
210 215 220
atc ctc aga ata ccc tca gtc tct aag aaa tac aaa gcc ttc tcc acc 720
Ile Leu Arg Ile Pro Ser Val Ser Lys Lys Tyr Lys Ala Phe Ser Thr
225 230 235 240
tgt gcc tcc cat ttg ggt gca gtc tcc ctc ttc tat ggg aca ctt tgt 768
Cys Ala Ser His Leu Gly Ala Val Ser Leu Phe Tyr Gly Thr Leu Cys
245 250 255
atg gta tac cta aag ccc ctc cat acc tac tct gtg aag gac tca gta 816
Met Val Tyr Leu Lys Pro Leu His Thr Tyr Ser Val Lys Asp Ser Val
260 265 270
gcc aca gtg atg tat gct gtg gtg aca ccc atg atg aat ccc ttc atc 864
Ala Thr Val Met Tyr Ala Val Val Thr Pro Met Met Asn Pro Phe Ile
275 280 285
tac agc ctg agg aac aag gac atg cat ggg gct ctg gga aga ctc cta 912
Tyr Ser Leu Arg Asn Lys Asp Met His Gly Ala Leu Gly Arg Leu Leu
290 295 300
gat aaa cac ttt aag agg ctg aca tga 939
Asp Lys His Phe Lys Arg Leu Thr
305 310
<210> 54
<211> 312
<212> PRT
<213> 智人
<400> 54
Met Asp Gly Gly Asn Gln Ser Glu Gly Ser Glu Phe Leu Leu Leu Gly
1 5 10 15
Met Ser Glu Ser Pro Glu Gln Gln Arg Ile Leu Phe Trp Met Phe Leu
20 25 30
Ser Met Tyr Leu Val Thr Val Val Gly Asn Val Leu Ile Ile Leu Ala
35 40 45
Ile Ser Ser Asp Ser Arg Leu His Thr Pro Val Tyr Phe Phe Leu Ala
50 55 60
Asn Leu Ser Phe Thr Asp Leu Phe Phe Val Thr Asn Thr Ile Pro Lys
65 70 75 80
Met Leu Val Asn Leu Gln Ser His Asn Lys Ala Ile Ser Tyr Ala Gly
85 90 95
Cys Leu Thr Gln Leu Tyr Phe Leu Val Ser Leu Val Ala Leu Asp Asn
100 105 110
Leu Ile Leu Ala Val Met Ala Tyr Asp Arg Tyr Val Ala Ile Cys Cys
115 120 125
Pro Leu His Tyr Thr Thr Ala Met Ser Pro Lys Leu Cys Ile Leu Leu
130 135 140
Leu Ser Leu Cys Trp Val Leu Ser Val Leu Tyr Gly Leu Ile His Thr
145 150 155 160
Leu Leu Met Thr Arg Val Thr Phe Cys Gly Ser Arg Lys Ile His Tyr
165 170 175
Ile Phe Cys Glu Met Tyr Val Leu Leu Arg Met Ala Cys Ser Asn Ile
180 185 190
Gln Ile Asn His Thr Val Leu Ile Ala Thr Gly Cys Phe Ile Phe Leu
195 200 205
Ile Pro Phe Gly Phe Val Ile Ile Ser Tyr Val Leu Ile Ile Arg Ala
210 215 220
Ile Leu Arg Ile Pro Ser Val Ser Lys Lys Tyr Lys Ala Phe Ser Thr
225 230 235 240
Cys Ala Ser His Leu Gly Ala Val Ser Leu Phe Tyr Gly Thr Leu Cys
245 250 255
Met Val Tyr Leu Lys Pro Leu His Thr Tyr Ser Val Lys Asp Ser Val
260 265 270
Ala Thr Val Met Tyr Ala Val Val Thr Pro Met Met Asn Pro Phe Ile
275 280 285
Tyr Ser Leu Arg Asn Lys Asp Met His Gly Ala Leu Gly Arg Leu Leu
290 295 300
Asp Lys His Phe Lys Arg Leu Thr
305 310
<210> 55
<211> 939
<212> DNA
<213> 智人
<220>
<221> CDS
<222> (1)..(939)
<400> 55
atg atg att aaa aaa aat gca agt tcg gaa gac ttc ttt att cta ctt 48
Met Met Ile Lys Lys Asn Ala Ser Ser Glu Asp Phe Phe Ile Leu Leu
1 5 10 15
gga ttt tct aat tgg cct cag ctg gaa gta gtt ctc ttt gtg gtt atc 96
Gly Phe Ser Asn Trp Pro Gln Leu Glu Val Val Leu Phe Val Val Ile
20 25 30
ttg atc ttc tac ctg atg aca ctg aca gga aac ctg ttc atc atc atc 144
Leu Ile Phe Tyr Leu Met Thr Leu Thr Gly Asn Leu Phe Ile Ile Ile
35 40 45
ctg tca tac gtg gac tcc cat ctc cac aca cca atg tac ttc ttc ctt 192
Leu Ser Tyr Val Asp Ser His Leu His Thr Pro Met Tyr Phe Phe Leu
50 55 60
tca aac ctc tca ttt ctg gat ctc tgc tac acc acc agc tct atc cct 240
Ser Asn Leu Ser Phe Leu Asp Leu Cys Tyr Thr Thr Ser Ser Ile Pro
65 70 75 80
cag ttg ctg gtg aat ctc cgg ggc ccg gaa aag acc atc tcg tat gct 288
Gln Leu Leu Val Asn Leu Arg Gly Pro Glu Lys Thr Ile Ser Tyr Ala
85 90 95
ggt tgc atg gtt caa ctt tac ttt gtt ctt gca ctg gga atc aca gag 336
Gly Cys Met Val Gln Leu Tyr Phe Val Leu Ala Leu Gly Ile Thr Glu
100 105 110
tgt gtc cta ctg gtg gtg atg tca tat gat cgt tat gta gct gtg tgt 384
Cys Val Leu Leu Val Val Met Ser Tyr Asp Arg Tyr Val Ala Val Cys
115 120 125
aga cct ttg cat tac act gtc ctc atg cac cct cgt ttc tgc cac ttg 432
Arg Pro Leu His Tyr Thr Val Leu Met His Pro Arg Phe Cys His Leu
130 135 140
ttg gtt gcg gct tct tgg gta att ggt ttt act atc tca gca ctt cat 480
Leu Val Ala Ala Ser Trp Val Ile Gly Phe Thr Ile Ser Ala Leu His
145 150 155 160
tcc tcc ttt act ttc tgg gta ccc ctt tgt gga cat cgc cta gtg gat 528
Ser Ser Phe Thr Phe Trp Val Pro Leu Cys Gly His Arg Leu Val Asp
165 170 175
cac ttc ttc tgt gaa gtt cca gca ctt ctg cgt tta tca tgt gtt gac 576
His Phe Phe Cys Glu Val Pro Ala Leu Leu Arg Leu Ser Cys Val Asp
180 185 190
acc cat gca aat gag ctg acc ctc atg gtc atg agc tcc att ttt gtt 624
Thr His Ala Asn Glu Leu Thr Leu Met Val Met Ser Ser Ile Phe Val
195 200 205
ctc ata cct ctc att ctc att ctc act acc tat ggt gcc att gcc cgg 672
Leu Ile Pro Leu Ile Leu Ile Leu Thr Thr Tyr Gly Ala Ile Ala Arg
210 215 220
gct gta ctg agc atg caa tca acc act ggg ctt cag aaa gtg ttt agg 720
Ala Val Leu Ser Met Gln Ser Thr Thr Gly Leu Gln Lys Val Phe Arg
225 230 235 240
aca tgt gga gcc cat ctt atg gtt gta tct ctc ttt ttc att cca gtc 768
Thr Cys Gly Ala His Leu Met Val Val Ser Leu Phe Phe Ile Pro Val
245 250 255
atg tgc atg tat ctc cag cca cca tca gaa aat tct cct gat cag ggc 816
Met Cys Met Tyr Leu Gln Pro Pro Ser Glu Asn Ser Pro Asp Gln Gly
260 265 270
aag ttc att gcc ctc ttt tat act gtt gtc aca ccg agt ctt aat cct 864
Lys Phe Ile Ala Leu Phe Tyr Thr Val Val Thr Pro Ser Leu Asn Pro
275 280 285
cta atc tac act ctc aga aac aag cat gta aaa ggg gca gcg aag aga 912
Leu Ile Tyr Thr Leu Arg Asn Lys His Val Lys Gly Ala Ala Lys Arg
290 295 300
cta ttg ggg tgg gag tgg ggg aag tga 939
Leu Leu Gly Trp Glu Trp Gly Lys
305 310
<210> 56
<211> 312
<212> PRT
<213> 智人
<400> 56
Met Met Ile Lys Lys Asn Ala Ser Ser Glu Asp Phe Phe Ile Leu Leu
1 5 10 15
Gly Phe Ser Asn Trp Pro Gln Leu Glu Val Val Leu Phe Val Val Ile
20 25 30
Leu Ile Phe Tyr Leu Met Thr Leu Thr Gly Asn Leu Phe Ile Ile Ile
35 40 45
Leu Ser Tyr Val Asp Ser His Leu His Thr Pro Met Tyr Phe Phe Leu
50 55 60
Ser Asn Leu Ser Phe Leu Asp Leu Cys Tyr Thr Thr Ser Ser Ile Pro
65 70 75 80
Gln Leu Leu Val Asn Leu Arg Gly Pro Glu Lys Thr Ile Ser Tyr Ala
85 90 95
Gly Cys Met Val Gln Leu Tyr Phe Val Leu Ala Leu Gly Ile Thr Glu
100 105 110
Cys Val Leu Leu Val Val Met Ser Tyr Asp Arg Tyr Val Ala Val Cys
115 120 125
Arg Pro Leu His Tyr Thr Val Leu Met His Pro Arg Phe Cys His Leu
130 135 140
Leu Val Ala Ala Ser Trp Val Ile Gly Phe Thr Ile Ser Ala Leu His
145 150 155 160
Ser Ser Phe Thr Phe Trp Val Pro Leu Cys Gly His Arg Leu Val Asp
165 170 175
His Phe Phe Cys Glu Val Pro Ala Leu Leu Arg Leu Ser Cys Val Asp
180 185 190
Thr His Ala Asn Glu Leu Thr Leu Met Val Met Ser Ser Ile Phe Val
195 200 205
Leu Ile Pro Leu Ile Leu Ile Leu Thr Thr Tyr Gly Ala Ile Ala Arg
210 215 220
Ala Val Leu Ser Met Gln Ser Thr Thr Gly Leu Gln Lys Val Phe Arg
225 230 235 240
Thr Cys Gly Ala His Leu Met Val Val Ser Leu Phe Phe Ile Pro Val
245 250 255
Met Cys Met Tyr Leu Gln Pro Pro Ser Glu Asn Ser Pro Asp Gln Gly
260 265 270
Lys Phe Ile Ala Leu Phe Tyr Thr Val Val Thr Pro Ser Leu Asn Pro
275 280 285
Leu Ile Tyr Thr Leu Arg Asn Lys His Val Lys Gly Ala Ala Lys Arg
290 295 300
Leu Leu Gly Trp Glu Trp Gly Lys
305 310
<210> 57
<211> 963
<212> DNA
<213> 智人
<220>
<221> CDS
<222> (1)..(963)
<400> 57
atg gac caa agc aat tat agt tct tta cat ggt ttt att ctg ctt ggc 48
Met Asp Gln Ser Asn Tyr Ser Ser Leu His Gly Phe Ile Leu Leu Gly
1 5 10 15
ttc tct aac cat cca aaa atg gag atg atc ctg tca gga gtt gtc gcc 96
Phe Ser Asn His Pro Lys Met Glu Met Ile Leu Ser Gly Val Val Ala
20 25 30
atc ttc tac tta att aca ttg gtg ggt aac aca gcc atc att ctt gca 144
Ile Phe Tyr Leu Ile Thr Leu Val Gly Asn Thr Ala Ile Ile Leu Ala
35 40 45
tct ctc ctg gat tcc cag ctt cat aca cca atg tac ttt ttc ctc aga 192
Ser Leu Leu Asp Ser Gln Leu His Thr Pro Met Tyr Phe Phe Leu Arg
50 55 60
aat tta tct ttc cta gat cta tgt ttc aca acc agc atc atc cct cag 240
Asn Leu Ser Phe Leu Asp Leu Cys Phe Thr Thr Ser Ile Ile Pro Gln
65 70 75 80
atg ctg gtc aac ttg tgg gga cct gat aag acc atc agc tat gtg ggt 288
Met Leu Val Asn Leu Trp Gly Pro Asp Lys Thr Ile Ser Tyr Val Gly
85 90 95
tgt atc atc caa ctc tat gtt tac atg tgg ttg ggc tca gtt gag tgc 336
Cys Ile Ile Gln Leu Tyr Val Tyr Met Trp Leu Gly Ser Val Glu Cys
100 105 110
ctt ctc ctg gct gtt atg tcc tat gat cgt ttt aca gct ata tgt aag 384
Leu Leu Leu Ala Val Met Ser Tyr Asp Arg Phe Thr Ala Ile Cys Lys
115 120 125
ccc ttg cat tat ttt gta gtc atg aac cca cat cta tgt cta aag atg 432
Pro Leu His Tyr Phe Val Val Met Asn Pro His Leu Cys Leu Lys Met
130 135 140
att atc atg atc tgg agt att agt ttg gcc aat tct gta gta tta tgt 480
Ile Ile Met Ile Trp Ser Ile Ser Leu Ala Asn Ser Val Val Leu Cys
145 150 155 160
aca ctc act ctg aat ttg ccc aca tgt gga aac aac att ctg gat cat 528
Thr Leu Thr Leu Asn Leu Pro Thr Cys Gly Asn Asn Ile Leu Asp His
165 170 175
ttc ttg tgt gag ttg cca gct ctg gtc aag ata gct tgt gta gac acc 576
Phe Leu Cys Glu Leu Pro Ala Leu Val Lys Ile Ala Cys Val Asp Thr
180 185 190
aca aca gtt gaa atg tct gtt ttc gct tta ggc att ata att gtc ctc 624
Thr Thr Val Glu Met Ser Val Phe Ala Leu Gly Ile Ile Ile Val Leu
195 200 205
aca cct ctc atc ctt att ctt ata tcc tat ggc tac att gcc aaa gct 672
Thr Pro Leu Ile Leu Ile Leu Ile Ser Tyr Gly Tyr Ile Ala Lys Ala
210 215 220
gtg ctg aga acg aag tca aaa gca agc cag cga aaa gca atg aat acc 720
Val Leu Arg Thr Lys Ser Lys Ala Ser Gln Arg Lys Ala Met Asn Thr
225 230 235 240
tgt gga tct cat ctt act gta gtg tct atg ttc tat gga act att atc 768
Cys Gly Ser His Leu Thr Val Val Ser Met Phe Tyr Gly Thr Ile Ile
245 250 255
tac atg tac ctg caa cca ggt aac agg gct tcc aaa gac cag ggc aag 816
Tyr Met Tyr Leu Gln Pro Gly Asn Arg Ala Ser Lys Asp Gln Gly Lys
260 265 270
ttc ctc acc ctc ttt tac acc gtc atc act cca agt ctc aac ccg ctc 864
Phe Leu Thr Leu Phe Tyr Thr Val Ile Thr Pro Ser Leu Asn Pro Leu
275 280 285
att tac acc tta aga aat aag gac atg aag gat gcc ctg aag aaa ctg 912
Ile Tyr Thr Leu Arg Asn Lys Asp Met Lys Asp Ala Leu Lys Lys Leu
290 295 300
atg aga ttt cac cac aaa tct aca aaa ata aag agg aat tgc aag tca 960
Met Arg Phe His His Lys Ser Thr Lys Ile Lys Arg Asn Cys Lys Ser
305 310 315 320
tag 963
<210> 58
<211> 320
<212> PRT
<213> 智人
<400> 58
Met Asp Gln Ser Asn Tyr Ser Ser Leu His Gly Phe Ile Leu Leu Gly
1 5 10 15
Phe Ser Asn His Pro Lys Met Glu Met Ile Leu Ser Gly Val Val Ala
20 25 30
Ile Phe Tyr Leu Ile Thr Leu Val Gly Asn Thr Ala Ile Ile Leu Ala
35 40 45
Ser Leu Leu Asp Ser Gln Leu His Thr Pro Met Tyr Phe Phe Leu Arg
50 55 60
Asn Leu Ser Phe Leu Asp Leu Cys Phe Thr Thr Ser Ile Ile Pro Gln
65 70 75 80
Met Leu Val Asn Leu Trp Gly Pro Asp Lys Thr Ile Ser Tyr Val Gly
85 90 95
Cys Ile Ile Gln Leu Tyr Val Tyr Met Trp Leu Gly Ser Val Glu Cys
100 105 110
Leu Leu Leu Ala Val Met Ser Tyr Asp Arg Phe Thr Ala Ile Cys Lys
115 120 125
Pro Leu His Tyr Phe Val Val Met Asn Pro His Leu Cys Leu Lys Met
130 135 140
Ile Ile Met Ile Trp Ser Ile Ser Leu Ala Asn Ser Val Val Leu Cys
145 150 155 160
Thr Leu Thr Leu Asn Leu Pro Thr Cys Gly Asn Asn Ile Leu Asp His
165 170 175
Phe Leu Cys Glu Leu Pro Ala Leu Val Lys Ile Ala Cys Val Asp Thr
180 185 190
Thr Thr Val Glu Met Ser Val Phe Ala Leu Gly Ile Ile Ile Val Leu
195 200 205
Thr Pro Leu Ile Leu Ile Leu Ile Ser Tyr Gly Tyr Ile Ala Lys Ala
210 215 220
Val Leu Arg Thr Lys Ser Lys Ala Ser Gln Arg Lys Ala Met Asn Thr
225 230 235 240
Cys Gly Ser His Leu Thr Val Val Ser Met Phe Tyr Gly Thr Ile Ile
245 250 255
Tyr Met Tyr Leu Gln Pro Gly Asn Arg Ala Ser Lys Asp Gln Gly Lys
260 265 270
Phe Leu Thr Leu Phe Tyr Thr Val Ile Thr Pro Ser Leu Asn Pro Leu
275 280 285
Ile Tyr Thr Leu Arg Asn Lys Asp Met Lys Asp Ala Leu Lys Lys Leu
290 295 300
Met Arg Phe His His Lys Ser Thr Lys Ile Lys Arg Asn Cys Lys Ser
305 310 315 320
<210> 59
<211> 2526
<212> DNA
<213> 智人
<220>
<221> CDS
<222> (1)..(2526)
<400> 59
atg ctg ctc tgc acg gct cgc ctg gtc ggc ctg cag ctt ctc att tcc 48
Met Leu Leu Cys Thr Ala Arg Leu Val Gly Leu Gln Leu Leu Ile Ser
1 5 10 15
tgc tgc tgg gcc ttt gcc tgc cat agc acg gag tct tct cct gac ttc 96
Cys Cys Trp Ala Phe Ala Cys His Ser Thr Glu Ser Ser Pro Asp Phe
20 25 30
acc ctc ccc gga gat tac ctc ctg gca ggc ctg ttc cct ctc cat tct 144
Thr Leu Pro Gly Asp Tyr Leu Leu Ala Gly Leu Phe Pro Leu His Ser
35 40 45
ggc tgt ctg cag gtg agg cac aga ccc gag gtg acc ctg tgt gac agg 192
Gly Cys Leu Gln Val Arg His Arg Pro Glu Val Thr Leu Cys Asp Arg
50 55 60
tct tgt agc ttc aat gag cat ggc tac cac ctc ttc cag gct atg cgg 240
Ser Cys Ser Phe Asn Glu His Gly Tyr His Leu Phe Gln Ala Met Arg
65 70 75 80
ctt ggg gtt gag gag ata aac aac tcc acg gcc ctg ctg ccc aac atc 288
Leu Gly Val Glu Glu Ile Asn Asn Ser Thr Ala Leu Leu Pro Asn Ile
85 90 95
acc ctg ggg tac cag ctg tat gat gtg tgt tct gac tct gcc aat gtg 336
Thr Leu Gly Tyr Gln Leu Tyr Asp Val Cys Ser Asp Ser Ala Asn Val
100 105 110
tat gcc acg ctg aga gtg ctc tcc ctg cca ggg caa cac cac ata gag 384
Tyr Ala Thr Leu Arg Val Leu Ser Leu Pro Gly Gln His His Ile Glu
115 120 125
ctc caa gga gac ctt ctc cac tat tcc cct acg gtg ctg gca gtg att 432
Leu Gln Gly Asp Leu Leu His Tyr Ser Pro Thr Val Leu Ala Val Ile
130 135 140
ggg cct gac agc acc aac cgt gct gcc acc aca gcc gcc ctg ctg agc 480
Gly Pro Asp Ser Thr Asn Arg Ala Ala Thr Thr Ala Ala Leu Leu Ser
145 150 155 160
cct ttc ctg gtg ccc atg att agc tat gcg gcc agc agc gag acg ctc 528
Pro Phe Leu Val Pro Met Ile Ser Tyr Ala Ala Ser Ser Glu Thr Leu
165 170 175
agc gtg aag cgg cag tat ccc tct ttc ctg cgc acc atc ccc aat gac 576
Ser Val Lys Arg Gln Tyr Pro Ser Phe Leu Arg Thr Ile Pro Asn Asp
180 185 190
aag tac cag gtg gag acc atg gtg ctg ctg ctg cag aag ttc ggg tgg 624
Lys Tyr Gln Val Glu Thr Met Val Leu Leu Leu Gln Lys Phe Gly Trp
195 200 205
acc tgg atc tct ctg gtt ggc agc agt gac gac tat ggg cag cta ggg 672
Thr Trp Ile Ser Leu Val Gly Ser Ser Asp Asp Tyr Gly Gln Leu Gly
210 215 220
gtg cag gca ctg gag aac cag gcc act ggt cag ggg atc tgc att gct 720
Val Gln Ala Leu Glu Asn Gln Ala Thr Gly Gln Gly Ile Cys Ile Ala
225 230 235 240
ttc aag gac atc atg ccc ttc tct gcc cag gtg ggc gat gag agg atg 768
Phe Lys Asp Ile Met Pro Phe Ser Ala Gln Val Gly Asp Glu Arg Met
245 250 255
cag tgc ctc atg cgc cac ctg gcc cag gcc ggg gcc acc gtc gtg gtt 816
Gln Cys Leu Met Arg His Leu Ala Gln Ala Gly Ala Thr Val Val Val
260 265 270
gtt ttt tcc agc cgg cag ttg gcc agg gtg ttt ttc gag tcc gtg gtg 864
Val Phe Ser Ser Arg Gln Leu Ala Arg Val Phe Phe Glu Ser Val Val
275 280 285
ctg acc aac ctg act ggc aag gtg tgg gtc gcc tca gaa gcc tgg gcc 912
Leu Thr Asn Leu Thr Gly Lys Val Trp Val Ala Ser Glu Ala Trp Ala
290 295 300
ctc tcc agg cac atc act ggg gtg ccc ggg atc cag cgc att ggg atg 960
Leu Ser Arg His Ile Thr Gly Val Pro Gly Ile Gln Arg Ile Gly Met
305 310 315 320
gtg ctg ggc gtg gcc atc cag aag agg gct gtc cct ggc ctg aag gcg 1008
Val Leu Gly Val Ala Ile Gln Lys Arg Ala Val Pro Gly Leu Lys Ala
325 330 335
ttt gaa gaa gcc tat gcc cgg gca gac aag aag gcc cct agg cct tgc 1056
Phe Glu Glu Ala Tyr Ala Arg Ala Asp Lys Lys Ala Pro Arg Pro Cys
340 345 350
cac aag ggc tcc tgg tgc agc agc aat cag ctc tgc aga gaa tgc caa 1104
His Lys Gly Ser Trp Cys Ser Ser Asn Gln Leu Cys Arg Glu Cys Gln
355 360 365
gct ttc atg gca cac acg atg ccc aag ctc aaa gcc ttc tcc atg agt 1152
Ala Phe Met Ala His Thr Met Pro Lys Leu Lys Ala Phe Ser Met Ser
370 375 380
tct gcc tac aac gca tac cgg gct gtg tat gcg gtg gcc cat ggc ctc 1200
Ser Ala Tyr Asn Ala Tyr Arg Ala Val Tyr Ala Val Ala His Gly Leu
385 390 395 400
cac cag ctc ctg ggc tgt gcc tct gga gct tgt tcc agg ggc cga gtc 1248
His Gln Leu Leu Gly Cys Ala Ser Gly Ala Cys Ser Arg Gly Arg Val
405 410 415
tac ccc tgg cag ctt ttg gag cag atc cac aag gtg cat ttc ctt cta 1296
Tyr Pro Trp Gln Leu Leu Glu Gln Ile His Lys Val His Phe Leu Leu
420 425 430
cac aag gac act gtg gcg ttt aat gac aac aga gat ccc ctc agt agc 1344
His Lys Asp Thr Val Ala Phe Asn Asp Asn Arg Asp Pro Leu Ser Ser
435 440 445
tat aac ata att gcc tgg gac tgg aat gga ccc aag tgg acc ttc acg 1392
Tyr Asn Ile Ile Ala Trp Asp Trp Asn Gly Pro Lys Trp Thr Phe Thr
450 455 460
gtc ctc ggt tcc tcc aca tgg tct cca gtt cag cta aac ata aat gag 1440
Val Leu Gly Ser Ser Thr Trp Ser Pro Val Gln Leu Asn Ile Asn Glu
465 470 475 480
acc aaa atc cag tgg cac gga aag gac aac cag gtg cct aag tct gtg 1488
Thr Lys Ile Gln Trp His Gly Lys Asp Asn Gln Val Pro Lys Ser Val
485 490 495
tgt tcc agc gac tgt ctt gaa ggg cac cag cga gtg gtt acg ggt ttc 1536
Cys Ser Ser Asp Cys Leu Glu Gly His Gln Arg Val Val Thr Gly Phe
500 505 510
cat cac tgc tgc ttt gag tgt gtg ccc tgt ggg gct ggg acc ttc ctc 1584
His His Cys Cys Phe Glu Cys Val Pro Cys Gly Ala Gly Thr Phe Leu
515 520 525
aac aag agt gac ctc tac aga tgc cag cct tgt ggg aaa gaa gag tgg 1632
Asn Lys Ser Asp Leu Tyr Arg Cys Gln Pro Cys Gly Lys Glu Glu Trp
530 535 540
gca cct gag gga agc cag acc tgc ttc ccg cgc act gtg gtg ttt ttg 1680
Ala Pro Glu Gly Ser Gln Thr Cys Phe Pro Arg Thr Val Val Phe Leu
545 550 555 560
gct ttg cgt gag cac acc tct tgg gtg ctg ctg gca gct aac acg ctg 1728
Ala Leu Arg Glu His Thr Ser Trp Val Leu Leu Ala Ala Asn Thr Leu
565 570 575
ctg ctg ctg ctg ctg ctt ggg act gct ggc ctg ttt gcc tgg cac cta 1776
Leu Leu Leu Leu Leu Leu Gly Thr Ala Gly Leu Phe Ala Trp His Leu
580 585 590
gac acc cct gtg gtg agg tca gca ggg ggc cgc ctg tgc ttt ctt atg 1824
Asp Thr Pro Val Val Arg Ser Ala Gly Gly Arg Leu Cys Phe Leu Met
595 600 605
ctg ggc tcc ctg gca gca ggt agt ggc agc ctc tat ggc ttc ttt ggg 1872
Leu Gly Ser Leu Ala Ala Gly Ser Gly Ser Leu Tyr Gly Phe Phe Gly
610 615 620
gaa ccc aca agg cct gcg tgc ttg cta cgc cag gcc ctc ttt gcc ctt 1920
Glu Pro Thr Arg Pro Ala Cys Leu Leu Arg Gln Ala Leu Phe Ala Leu
625 630 635 640
ggt ttc acc atc ttc ctg tcc tgc ctg aca gtt cgc tca ttc caa cta 1968
Gly Phe Thr Ile Phe Leu Ser Cys Leu Thr Val Arg Ser Phe Gln Leu
645 650 655
atc atc atc ttc aag ttt tcc acc aag gta cct aca ttc tac cac gcc 2016
Ile Ile Ile Phe Lys Phe Ser Thr Lys Val Pro Thr Phe Tyr His Ala
660 665 670
tgg gtc caa aac cac ggt gct ggc ctg ttt gtg atg atc agc tca gcg 2064
Trp Val Gln Asn His Gly Ala Gly Leu Phe Val Met Ile Ser Ser Ala
675 680 685
gcc cag ctg ctt atc tgt cta act tgg ctg gtg gtg tgg acc cca ctg 2112
Ala Gln Leu Leu Ile Cys Leu Thr Trp Leu Val Val Trp Thr Pro Leu
690 695 700
cct gct agg gaa tac cag cgc ttc ccc cat ctg gtg atg ctt gag tgc 2160
Pro Ala Arg Glu Tyr Gln Arg Phe Pro His Leu Val Met Leu Glu Cys
705 710 715 720
aca gag acc aac tcc ctg ggc ttc ata ctg gcc ttc ctc tac aat ggc 2208
Thr Glu Thr Asn Ser Leu Gly Phe Ile Leu Ala Phe Leu Tyr Asn Gly
725 730 735
ctc ctc tcc atc agt gcc ttt gcc tgc agc tac ctg ggt aag gac ttg 2256
Leu Leu Ser Ile Ser Ala Phe Ala Cys Ser Tyr Leu Gly Lys Asp Leu
740 745 750
cca gag aac tac aac gag gcc aaa tgt gtc acc ttc agc ctg ctc ttc 2304
Pro Glu Asn Tyr Asn Glu Ala Lys Cys Val Thr Phe Ser Leu Leu Phe
755 760 765
aac ttc gtg tcc tgg atc gcc ttc ttc acc acg gcc agc gtc tac gac 2352
Asn Phe Val Ser Trp Ile Ala Phe Phe Thr Thr Ala Ser Val Tyr Asp
770 775 780
ggc aag tac ctg cct gcg gcc aac atg atg gct ggg ctg agc agc ctg 2400
Gly Lys Tyr Leu Pro Ala Ala Asn Met Met Ala Gly Leu Ser Ser Leu
785 790 795 800
agc agc ggc ttc ggt ggg tat ttt ctg cct aag tgc tac gtg atc ctc 2448
Ser Ser Gly Phe Gly Gly Tyr Phe Leu Pro Lys Cys Tyr Val Ile Leu
805 810 815
tgc cgc cca gac ctc aac agc aca gag cac ttc cag gcc tcc att cag 2496
Cys Arg Pro Asp Leu Asn Ser Thr Glu His Phe Gln Ala Ser Ile Gln
820 825 830
gac tac acg agg cgc tgc ggc tcc acc tga 2526
Asp Tyr Thr Arg Arg Cys Gly Ser Thr
835 840
<210> 60
<211> 841
<212> PRT
<213> 智人
<400> 60
Met Leu Leu Cys Thr Ala Arg Leu Val Gly Leu Gln Leu Leu Ile Ser
1 5 10 15
Cys Cys Trp Ala Phe Ala Cys His Ser Thr Glu Ser Ser Pro Asp Phe
20 25 30
Thr Leu Pro Gly Asp Tyr Leu Leu Ala Gly Leu Phe Pro Leu His Ser
35 40 45
Gly Cys Leu Gln Val Arg His Arg Pro Glu Val Thr Leu Cys Asp Arg
50 55 60
Ser Cys Ser Phe Asn Glu His Gly Tyr His Leu Phe Gln Ala Met Arg
65 70 75 80
Leu Gly Val Glu Glu Ile Asn Asn Ser Thr Ala Leu Leu Pro Asn Ile
85 90 95
Thr Leu Gly Tyr Gln Leu Tyr Asp Val Cys Ser Asp Ser Ala Asn Val
100 105 110
Tyr Ala Thr Leu Arg Val Leu Ser Leu Pro Gly Gln His His Ile Glu
115 120 125
Leu Gln Gly Asp Leu Leu His Tyr Ser Pro Thr Val Leu Ala Val Ile
130 135 140
Gly Pro Asp Ser Thr Asn Arg Ala Ala Thr Thr Ala Ala Leu Leu Ser
145 150 155 160
Pro Phe Leu Val Pro Met Ile Ser Tyr Ala Ala Ser Ser Glu Thr Leu
165 170 175
Ser Val Lys Arg Gln Tyr Pro Ser Phe Leu Arg Thr Ile Pro Asn Asp
180 185 190
Lys Tyr Gln Val Glu Thr Met Val Leu Leu Leu Gln Lys Phe Gly Trp
195 200 205
Thr Trp Ile Ser Leu Val Gly Ser Ser Asp Asp Tyr Gly Gln Leu Gly
210 215 220
Val Gln Ala Leu Glu Asn Gln Ala Thr Gly Gln Gly Ile Cys Ile Ala
225 230 235 240
Phe Lys Asp Ile Met Pro Phe Ser Ala Gln Val Gly Asp Glu Arg Met
245 250 255
Gln Cys Leu Met Arg His Leu Ala Gln Ala Gly Ala Thr Val Val Val
260 265 270
Val Phe Ser Ser Arg Gln Leu Ala Arg Val Phe Phe Glu Ser Val Val
275 280 285
Leu Thr Asn Leu Thr Gly Lys Val Trp Val Ala Ser Glu Ala Trp Ala
290 295 300
Leu Ser Arg His Ile Thr Gly Val Pro Gly Ile Gln Arg Ile Gly Met
305 310 315 320
Val Leu Gly Val Ala Ile Gln Lys Arg Ala Val Pro Gly Leu Lys Ala
325 330 335
Phe Glu Glu Ala Tyr Ala Arg Ala Asp Lys Lys Ala Pro Arg Pro Cys
340 345 350
His Lys Gly Ser Trp Cys Ser Ser Asn Gln Leu Cys Arg Glu Cys Gln
355 360 365
Ala Phe Met Ala His Thr Met Pro Lys Leu Lys Ala Phe Ser Met Ser
370 375 380
Ser Ala Tyr Asn Ala Tyr Arg Ala Val Tyr Ala Val Ala His Gly Leu
385 390 395 400
His Gln Leu Leu Gly Cys Ala Ser Gly Ala Cys Ser Arg Gly Arg Val
405 410 415
Tyr Pro Trp Gln Leu Leu Glu Gln Ile His Lys Val His Phe Leu Leu
420 425 430
His Lys Asp Thr Val Ala Phe Asn Asp Asn Arg Asp Pro Leu Ser Ser
435 440 445
Tyr Asn Ile Ile Ala Trp Asp Trp Asn Gly Pro Lys Trp Thr Phe Thr
450 455 460
Val Leu Gly Ser Ser Thr Trp Ser Pro Val Gln Leu Asn Ile Asn Glu
465 470 475 480
Thr Lys Ile Gln Trp His Gly Lys Asp Asn Gln Val Pro Lys Ser Val
485 490 495
Cys Ser Ser Asp Cys Leu Glu Gly His Gln Arg Val Val Thr Gly Phe
500 505 510
His His Cys Cys Phe Glu Cys Val Pro Cys Gly Ala Gly Thr Phe Leu
515 520 525
Asn Lys Ser Asp Leu Tyr Arg Cys Gln Pro Cys Gly Lys Glu Glu Trp
530 535 540
Ala Pro Glu Gly Ser Gln Thr Cys Phe Pro Arg Thr Val Val Phe Leu
545 550 555 560
Ala Leu Arg Glu His Thr Ser Trp Val Leu Leu Ala Ala Asn Thr Leu
565 570 575
Leu Leu Leu Leu Leu Leu Gly Thr Ala Gly Leu Phe Ala Trp His Leu
580 585 590
Asp Thr Pro Val Val Arg Ser Ala Gly Gly Arg Leu Cys Phe Leu Met
595 600 605
Leu Gly Ser Leu Ala Ala Gly Ser Gly Ser Leu Tyr Gly Phe Phe Gly
610 615 620
Glu Pro Thr Arg Pro Ala Cys Leu Leu Arg Gln Ala Leu Phe Ala Leu
625 630 635 640
Gly Phe Thr Ile Phe Leu Ser Cys Leu Thr Val Arg Ser Phe Gln Leu
645 650 655
Ile Ile Ile Phe Lys Phe Ser Thr Lys Val Pro Thr Phe Tyr His Ala
660 665 670
Trp Val Gln Asn His Gly Ala Gly Leu Phe Val Met Ile Ser Ser Ala
675 680 685
Ala Gln Leu Leu Ile Cys Leu Thr Trp Leu Val Val Trp Thr Pro Leu
690 695 700
Pro Ala Arg Glu Tyr Gln Arg Phe Pro His Leu Val Met Leu Glu Cys
705 710 715 720
Thr Glu Thr Asn Ser Leu Gly Phe Ile Leu Ala Phe Leu Tyr Asn Gly
725 730 735
Leu Leu Ser Ile Ser Ala Phe Ala Cys Ser Tyr Leu Gly Lys Asp Leu
740 745 750
Pro Glu Asn Tyr Asn Glu Ala Lys Cys Val Thr Phe Ser Leu Leu Phe
755 760 765
Asn Phe Val Ser Trp Ile Ala Phe Phe Thr Thr Ala Ser Val Tyr Asp
770 775 780
Gly Lys Tyr Leu Pro Ala Ala Asn Met Met Ala Gly Leu Ser Ser Leu
785 790 795 800
Ser Ser Gly Phe Gly Gly Tyr Phe Leu Pro Lys Cys Tyr Val Ile Leu
805 810 815
Cys Arg Pro Asp Leu Asn Ser Thr Glu His Phe Gln Ala Ser Ile Gln
820 825 830
Asp Tyr Thr Arg Arg Cys Gly Ser Thr
835 840
<210> 61
<211> 2520
<212> DNA
<213> 智人
<220>
<221> CDS
<222> (1)..(2520)
<400> 61
atg ggg ccc agg gca aag acc atc tcc tcc ctg ttc ttc ctc cta tgg 48
Met Gly Pro Arg Ala Lys Thr Ile Ser Ser Leu Phe Phe Leu Leu Trp
1 5 10 15
gtc ctg gct gag ccg gct gag aac tcg gac ttc tac ctg cct ggg gat 96
Val Leu Ala Glu Pro Ala Glu Asn Ser Asp Phe Tyr Leu Pro Gly Asp
20 25 30
tac ctc ctg ggt ggc ctc ttc tcc ctc cat gcc aac atg aag ggc att 144
Tyr Leu Leu Gly Gly Leu Phe Ser Leu His Ala Asn Met Lys Gly Ile
35 40 45
gtt cac ctt aac ttc ctg cag gtg ccc atg tgc aag gag tat gaa gtg 192
Val His Leu Asn Phe Leu Gln Val Pro Met Cys Lys Glu Tyr Glu Val
50 55 60
aag gtg ata ggc tac aac ctc atg cag gcc atg cgc ttt gcg gtg gag 240
Lys Val Ile Gly Tyr Asn Leu Met Gln Ala Met Arg Phe Ala Val Glu
65 70 75 80
gag atc aac aat gac agc agc ctg ctg cct ggt gtg ctg ctg ggc tat 288
Glu Ile Asn Asn Asp Ser Ser Leu Leu Pro Gly Val Leu Leu Gly Tyr
85 90 95
gag atc gtg gat gtg tgc tac atc tcc aac aat gtc cag ccg gtg ctc 336
Glu Ile Val Asp Val Cys Tyr Ile Ser Asn Asn Val Gln Pro Val Leu
100 105 110
tac ttc ctg gca cac gag gac aac ctc ctt ccc atc caa gag gac tac 384
Tyr Phe Leu Ala His Glu Asp Asn Leu Leu Pro Ile Gln Glu Asp Tyr
115 120 125
agt aac tac att tcc cgt gtg gtg gct gtc att ggc cct gac aac tcc 432
Ser Asn Tyr Ile Ser Arg Val Val Ala Val Ile Gly Pro Asp Asn Ser
130 135 140
gag tct gtc atg act gtg gcc aac ttc ctc tcc cta ttt ctc ctt cca 480
Glu Ser Val Met Thr Val Ala Asn Phe Leu Ser Leu Phe Leu Leu Pro
145 150 155 160
cag atc acc tac agc gcc atc agc gat gag ctg cga gac aag gtg cgc 528
Gln Ile Thr Tyr Ser Ala Ile Ser Asp Glu Leu Arg Asp Lys Val Arg
165 170 175
ttc ccg gct ttg ctg cgt acc aca ccc agc gcc gac cac cac atc gag 576
Phe Pro Ala Leu Leu Arg Thr Thr Pro Ser Ala Asp His His Ile Glu
180 185 190
gcc atg gtg cag ctg atg ctg cac ttc cgc tgg aac tgg atc att gtg 624
Ala Met Val Gln Leu Met Leu His Phe Arg Trp Asn Trp Ile Ile Val
195 200 205
ctg gtg agc agc gac acc tat ggc cgc gac aat ggc cag ctg ctt ggc 672
Leu Val Ser Ser Asp Thr Tyr Gly Arg Asp Asn Gly Gln Leu Leu Gly
210 215 220
gag cgc gtg gcc cgg cgc gac atc tgc atc gcc ttc cag gag acg ctg 720
Glu Arg Val Ala Arg Arg Asp Ile Cys Ile Ala Phe Gln Glu Thr Leu
225 230 235 240
ccc aca ctg cag ccc aac cag aac atg acg tca gag gag cgc cag cgc 768
Pro Thr Leu Gln Pro Asn Gln Asn Met Thr Ser Glu Glu Arg Gln Arg
245 250 255
ctg gtg acc att gtg gac aag ctg cag cag agc aca gcg cgc gtc gtg 816
Leu Val Thr Ile Val Asp Lys Leu Gln Gln Ser Thr Ala Arg Val Val
260 265 270
gtc gtg ttc tcg ccc gac ctg acc ctg tac cac ttc ttc aat gag gtg 864
Val Val Phe Ser Pro Asp Leu Thr Leu Tyr His Phe Phe Asn Glu Val
275 280 285
ctg cgc cag aac ttc act ggc gcc gtg tgg atc gcc tcc gag tcc tgg 912
Leu Arg Gln Asn Phe Thr Gly Ala Val Trp Ile Ala Ser Glu Ser Trp
290 295 300
gcc atc gac ccg gtc ctg cac aac ctc acg gag ctg cgc cac ttg ggc 960
Ala Ile Asp Pro Val Leu His Asn Leu Thr Glu Leu Arg His Leu Gly
305 310 315 320
acc ttc ctg ggc atc acc atc cag agc gtg ccc atc ccg ggc ttc agt 1008
Thr Phe Leu Gly Ile Thr Ile Gln Ser Val Pro Ile Pro Gly Phe Ser
325 330 335
gag ttc cgc gag tgg ggc cca cag gct ggg ccg cca ccc ctc agc agg 1056
Glu Phe Arg Glu Trp Gly Pro Gln Ala Gly Pro Pro Pro Leu Ser Arg
340 345 350
acc agc cag agc tat acc tgc aac cag gag tgc gac aac tgc ctg aac 1104
Thr Ser Gln Ser Tyr Thr Cys Asn Gln Glu Cys Asp Asn Cys Leu Asn
355 360 365
gcc acc ttg tcc ttc aac acc att ctc agg ctc tct ggg gag cgt gtc 1152
Ala Thr Leu Ser Phe Asn Thr Ile Leu Arg Leu Ser Gly Glu Arg Val
370 375 380
gtc tac agc gtg tac tct gcg gtc tat gct gtg gcc cat gcc ctg cac 1200
Val Tyr Ser Val Tyr Ser Ala Val Tyr Ala Val Ala His Ala Leu His
385 390 395 400
agc ctc ctc ggc tgt gac aaa agc acc tgc acc aag agg gtg gtc tac 1248
Ser Leu Leu Gly Cys Asp Lys Ser Thr Cys Thr Lys Arg Val Val Tyr
405 410 415
ccc tgg cag ctg ctt gag gag atc tgg aag gtc aac ttc act ctc ctg 1296
Pro Trp Gln Leu Leu Glu Glu Ile Trp Lys Val Asn Phe Thr Leu Leu
420 425 430
gac cac caa atc ttc ttc gac ccg caa ggg gac gtg gct ctg cac ttg 1344
Asp His Gln Ile Phe Phe Asp Pro Gln Gly Asp Val Ala Leu His Leu
435 440 445
gag att gtc cag tgg caa tgg gac cgg agc cag aat ccc ttc cag agc 1392
Glu Ile Val Gln Trp Gln Trp Asp Arg Ser Gln Asn Pro Phe Gln Ser
450 455 460
gtc gcc tcc tac tac ccc ctg cag cga cag ctg aag aac atc caa gac 1440
Val Ala Ser Tyr Tyr Pro Leu Gln Arg Gln Leu Lys Asn Ile Gln Asp
465 470 475 480
atc tcc tgg cac acc atc aac aac acg atc cct atg tcc atg tgt tcc 1488
Ile Ser Trp His Thr Ile Asn Asn Thr Ile Pro Met Ser Met Cys Ser
485 490 495
aag agg tgc cag tca ggg caa aag aag aag cct gtg ggc atc cac gtc 1536
Lys Arg Cys Gln Ser Gly Gln Lys Lys Lys Pro Val Gly Ile His Val
500 505 510
tgc tgc ttc gag tgc atc gac tgc ctt ccc ggc acc ttc ctc aac cac 1584
Cys Cys Phe Glu Cys Ile Asp Cys Leu Pro Gly Thr Phe Leu Asn His
515 520 525
act gaa gat gaa tat gaa tgc cag gcc tgc ccg aat aac gag tgg tcc 1632
Thr Glu Asp Glu Tyr Glu Cys Gln Ala Cys Pro Asn Asn Glu Trp Ser
530 535 540
tac cag agt gag acc tcc tgc ttc aag cgg cag ctg gtc ttc ctg gaa 1680
Tyr Gln Ser Glu Thr Ser Cys Phe Lys Arg Gln Leu Val Phe Leu Glu
545 550 555 560
tgg cat gag gca ccc acc atc gct gtg gcc ctg ctg gcc gcc ctg ggc 1728
Trp His Glu Ala Pro Thr Ile Ala Val Ala Leu Leu Ala Ala Leu Gly
565 570 575
ttc ctc agc acc ctg gcc atc ctg gtg ata ttc tgg agg cac ttc cag 1776
Phe Leu Ser Thr Leu Ala Ile Leu Val Ile Phe Trp Arg His Phe Gln
580 585 590
aca ccc ata gtt cgc tcg gct ggg ggc ccc atg tgc ttc ctg atg ctg 1824
Thr Pro Ile Val Arg Ser Ala Gly Gly Pro Met Cys Phe Leu Met Leu
595 600 605
aca ctg ctg ctg gtg gca tac atg gtg gtc ccg gtg tac gtg ggg ccg 1872
Thr Leu Leu Leu Val Ala Tyr Met Val Val Pro Val Tyr Val Gly Pro
610 615 620
ccc aag gtc tcc acc tgc ctc tgc cgc cag gcc ctc ttt ccc ctc tgc 1920
Pro Lys Val Ser Thr Cys Leu Cys Arg Gln Ala Leu Phe Pro Leu Cys
625 630 635 640
ttc aca atc tgc atc tcc tgt atc gcc gtg cgt tct ttc cag atc gtc 1968
Phe Thr Ile Cys Ile Ser Cys Ile Ala Val Arg Ser Phe Gln Ile Val
645 650 655
tgc gcc ttc aag atg gcc agc cgc ttc cca cgc gcc tac agc tac tgg 2016
Cys Ala Phe Lys Met Ala Ser Arg Phe Pro Arg Ala Tyr Ser Tyr Trp
660 665 670
gtc cgc tac cag ggg ccc tac gtc tct atg gca ttt atc acg gta ctc 2064
Val Arg Tyr Gln Gly Pro Tyr Val Ser Met Ala Phe Ile Thr Val Leu
675 680 685
aaa atg gtc att gtg gta att ggc atg ctg gcc acg ggc ctc agt ccc 2112
Lys Met Val Ile Val Val Ile Gly Met Leu Ala Thr Gly Leu Ser Pro
690 695 700
acc acc cgt act gac ccc gat gac ccc aag atc aca att gtc tcc tgt 2160
Thr Thr Arg Thr Asp Pro Asp Asp Pro Lys Ile Thr Ile Val Ser Cys
705 710 715 720
aac ccc aac tac cgc aac agc ctg ctg ttc aac acc agc ctg gac ctg 2208
Asn Pro Asn Tyr Arg Asn Ser Leu Leu Phe Asn Thr Ser Leu Asp Leu
725 730 735
ctg ctc tca gtg gtg ggt ttc agc ttc gcc tac atg ggc aaa gag ctg 2256
Leu Leu Ser Val Val Gly Phe Ser Phe Ala Tyr Met Gly Lys Glu Leu
740 745 750
ccc acc aac tac aac gag gcc aag ttc atc acc ctc agc atg acc ttc 2304
Pro Thr Asn Tyr Asn Glu Ala Lys Phe Ile Thr Leu Ser Met Thr Phe
755 760 765
tat ttc acc tca tcc gtc tcc ctc tgc acc ttc atg tct gcc tac agc 2352
Tyr Phe Thr Ser Ser Val Ser Leu Cys Thr Phe Met Ser Ala Tyr Ser
770 775 780
ggg gtg ctg gtc acc atc gtg gac ctc ttg gtc act gtg ctc aac ctc 2400
Gly Val Leu Val Thr Ile Val Asp Leu Leu Val Thr Val Leu Asn Leu
785 790 795 800
ctg gcc atc agc ctg ggc tac ttc ggc ccc aag tgc tac atg atc ctc 2448
Leu Ala Ile Ser Leu Gly Tyr Phe Gly Pro Lys Cys Tyr Met Ile Leu
805 810 815
ttc tac ccg gag cgc aac acg ccc gcc tac ttc aac agc atg atc cag 2496
Phe Tyr Pro Glu Arg Asn Thr Pro Ala Tyr Phe Asn Ser Met Ile Gln
820 825 830
ggc tac acc atg agg agg gac tag 2520
Gly Tyr Thr Met Arg Arg Asp
835
<210> 62
<211> 839
<212> PRT
<213> 智人
<400> 62
Met Gly Pro Arg Ala Lys Thr Ile Ser Ser Leu Phe Phe Leu Leu Trp
1 5 10 15
Val Leu Ala Glu Pro Ala Glu Asn Ser Asp Phe Tyr Leu Pro Gly Asp
20 25 30
Tyr Leu Leu Gly Gly Leu Phe Ser Leu His Ala Asn Met Lys Gly Ile
35 40 45
Val His Leu Asn Phe Leu Gln Val Pro Met Cys Lys Glu Tyr Glu Val
50 55 60
Lys Val Ile Gly Tyr Asn Leu Met Gln Ala Met Arg Phe Ala Val Glu
65 70 75 80
Glu Ile Asn Asn Asp Ser Ser Leu Leu Pro Gly Val Leu Leu Gly Tyr
85 90 95
Glu Ile Val Asp Val Cys Tyr Ile Ser Asn Asn Val Gln Pro Val Leu
100 105 110
Tyr Phe Leu Ala His Glu Asp Asn Leu Leu Pro Ile Gln Glu Asp Tyr
115 120 125
Ser Asn Tyr Ile Ser Arg Val Val Ala Val Ile Gly Pro Asp Asn Ser
130 135 140
Glu Ser Val Met Thr Val Ala Asn Phe Leu Ser Leu Phe Leu Leu Pro
145 150 155 160
Gln Ile Thr Tyr Ser Ala Ile Ser Asp Glu Leu Arg Asp Lys Val Arg
165 170 175
Phe Pro Ala Leu Leu Arg Thr Thr Pro Ser Ala Asp His His Ile Glu
180 185 190
Ala Met Val Gln Leu Met Leu His Phe Arg Trp Asn Trp Ile Ile Val
195 200 205
Leu Val Ser Ser Asp Thr Tyr Gly Arg Asp Asn Gly Gln Leu Leu Gly
210 215 220
Glu Arg Val Ala Arg Arg Asp Ile Cys Ile Ala Phe Gln Glu Thr Leu
225 230 235 240
Pro Thr Leu Gln Pro Asn Gln Asn Met Thr Ser Glu Glu Arg Gln Arg
245 250 255
Leu Val Thr Ile Val Asp Lys Leu Gln Gln Ser Thr Ala Arg Val Val
260 265 270
Val Val Phe Ser Pro Asp Leu Thr Leu Tyr His Phe Phe Asn Glu Val
275 280 285
Leu Arg Gln Asn Phe Thr Gly Ala Val Trp Ile Ala Ser Glu Ser Trp
290 295 300
Ala Ile Asp Pro Val Leu His Asn Leu Thr Glu Leu Arg His Leu Gly
305 310 315 320
Thr Phe Leu Gly Ile Thr Ile Gln Ser Val Pro Ile Pro Gly Phe Ser
325 330 335
Glu Phe Arg Glu Trp Gly Pro Gln Ala Gly Pro Pro Pro Leu Ser Arg
340 345 350
Thr Ser Gln Ser Tyr Thr Cys Asn Gln Glu Cys Asp Asn Cys Leu Asn
355 360 365
Ala Thr Leu Ser Phe Asn Thr Ile Leu Arg Leu Ser Gly Glu Arg Val
370 375 380
Val Tyr Ser Val Tyr Ser Ala Val Tyr Ala Val Ala His Ala Leu His
385 390 395 400
Ser Leu Leu Gly Cys Asp Lys Ser Thr Cys Thr Lys Arg Val Val Tyr
405 410 415
Pro Trp Gln Leu Leu Glu Glu Ile Trp Lys Val Asn Phe Thr Leu Leu
420 425 430
Asp His Gln Ile Phe Phe Asp Pro Gln Gly Asp Val Ala Leu His Leu
435 440 445
Glu Ile Val Gln Trp Gln Trp Asp Arg Ser Gln Asn Pro Phe Gln Ser
450 455 460
Val Ala Ser Tyr Tyr Pro Leu Gln Arg Gln Leu Lys Asn Ile Gln Asp
465 470 475 480
Ile Ser Trp His Thr Ile Asn Asn Thr Ile Pro Met Ser Met Cys Ser
485 490 495
Lys Arg Cys Gln Ser Gly Gln Lys Lys Lys Pro Val Gly Ile His Val
500 505 510
Cys Cys Phe Glu Cys Ile Asp Cys Leu Pro Gly Thr Phe Leu Asn His
515 520 525
Thr Glu Asp Glu Tyr Glu Cys Gln Ala Cys Pro Asn Asn Glu Trp Ser
530 535 540
Tyr Gln Ser Glu Thr Ser Cys Phe Lys Arg Gln Leu Val Phe Leu Glu
545 550 555 560
Trp His Glu Ala Pro Thr Ile Ala Val Ala Leu Leu Ala Ala Leu Gly
565 570 575
Phe Leu Ser Thr Leu Ala Ile Leu Val Ile Phe Trp Arg His Phe Gln
580 585 590
Thr Pro Ile Val Arg Ser Ala Gly Gly Pro Met Cys Phe Leu Met Leu
595 600 605
Thr Leu Leu Leu Val Ala Tyr Met Val Val Pro Val Tyr Val Gly Pro
610 615 620
Pro Lys Val Ser Thr Cys Leu Cys Arg Gln Ala Leu Phe Pro Leu Cys
625 630 635 640
Phe Thr Ile Cys Ile Ser Cys Ile Ala Val Arg Ser Phe Gln Ile Val
645 650 655
Cys Ala Phe Lys Met Ala Ser Arg Phe Pro Arg Ala Tyr Ser Tyr Trp
660 665 670
Val Arg Tyr Gln Gly Pro Tyr Val Ser Met Ala Phe Ile Thr Val Leu
675 680 685
Lys Met Val Ile Val Val Ile Gly Met Leu Ala Thr Gly Leu Ser Pro
690 695 700
Thr Thr Arg Thr Asp Pro Asp Asp Pro Lys Ile Thr Ile Val Ser Cys
705 710 715 720
Asn Pro Asn Tyr Arg Asn Ser Leu Leu Phe Asn Thr Ser Leu Asp Leu
725 730 735
Leu Leu Ser Val Val Gly Phe Ser Phe Ala Tyr Met Gly Lys Glu Leu
740 745 750
Pro Thr Asn Tyr Asn Glu Ala Lys Phe Ile Thr Leu Ser Met Thr Phe
755 760 765
Tyr Phe Thr Ser Ser Val Ser Leu Cys Thr Phe Met Ser Ala Tyr Ser
770 775 780
Gly Val Leu Val Thr Ile Val Asp Leu Leu Val Thr Val Leu Asn Leu
785 790 795 800
Leu Ala Ile Ser Leu Gly Tyr Phe Gly Pro Lys Cys Tyr Met Ile Leu
805 810 815
Phe Tyr Pro Glu Arg Asn Thr Pro Ala Tyr Phe Asn Ser Met Ile Gln
820 825 830
Gly Tyr Thr Met Arg Arg Asp
835
<210> 63
<211> 2559
<212> DNA
<213> 智人
<220>
<221> CDS
<222> (1)..(2559)
<400> 63
atg ctg ggc cct gct gtc ctg ggc ctc agc ctc tgg gct ctc ctg cac 48
Met Leu Gly Pro Ala Val Leu Gly Leu Ser Leu Trp Ala Leu Leu His
1 5 10 15
cct ggg acg ggg gcc cca ttg tgc ctg tca cag caa ctt agg atg aag 96
Pro Gly Thr Gly Ala Pro Leu Cys Leu Ser Gln Gln Leu Arg Met Lys
20 25 30
ggg gac tac gtg ctg ggg ggg ctg ttc ccc ctg ggc gag gcc gag gag 144
Gly Asp Tyr Val Leu Gly Gly Leu Phe Pro Leu Gly Glu Ala Glu Glu
35 40 45
gct ggc ctc cgc agc cgg aca cgg ccc agc agc cct gtg tgc acc agg 192
Ala Gly Leu Arg Ser Arg Thr Arg Pro Ser Ser Pro Val Cys Thr Arg
50 55 60
ttc tcc tca aac ggc ctg ctc tgg gca ctg gcc atg aaa atg gcc gtg 240
Phe Ser Ser Asn Gly Leu Leu Trp Ala Leu Ala Met Lys Met Ala Val
65 70 75 80
gag gag atc aac aac aag tcg gat ctg ctg ccc ggg ctg cgc ctg ggc 288
Glu Glu Ile Asn Asn Lys Ser Asp Leu Leu Pro Gly Leu Arg Leu Gly
85 90 95
tac gac ctc ttt gat acg tgc tcg gag cct gtg gtg gcc atg aag ccc 336
Tyr Asp Leu Phe Asp Thr Cys Ser Glu Pro Val Val Ala Met Lys Pro
100 105 110
agc ctc atg ttc ctg gcc aag gca ggc agc cgc gac atc gcc gcc tac 384
Ser Leu Met Phe Leu Ala Lys Ala Gly Ser Arg Asp Ile Ala Ala Tyr
115 120 125
tgc aac tac acg cag tac cag ccc cgt gtg ctg gct gtc atc ggg ccc 432
Cys Asn Tyr Thr Gln Tyr Gln Pro Arg Val Leu Ala Val Ile Gly Pro
130 135 140
cac tcg tca gag ctc gcc atg gtc acc ggc aag ttc ttc agc ttc ttc 480
His Ser Ser Glu Leu Ala Met Val Thr Gly Lys Phe Phe Ser Phe Phe
145 150 155 160
ctc atg ccc cag gtc agc tac ggt gct agc atg gag ctg ctg agc gcc 528
Leu Met Pro Gln Val Ser Tyr Gly Ala Ser Met Glu Leu Leu Ser Ala
165 170 175
cgg gag acc ttc ccc tcc ttc ttc cgc acc gtg ccc agc gac cgt gtg 576
Arg Glu Thr Phe Pro Ser Phe Phe Arg Thr Val Pro Ser Asp Arg Val
180 185 190
cag ctg acg gcc gcc gcg gag ctg ctg cag gag ttc ggc tgg aac tgg 624
Gln Leu Thr Ala Ala Ala Glu Leu Leu Gln Glu Phe Gly Trp Asn Trp
195 200 205
gtg gcc gcc ctg ggc agc gac gac gag tac ggc cgg cag ggc ctg agc 672
Val Ala Ala Leu Gly Ser Asp Asp Glu Tyr Gly Arg Gln Gly Leu Ser
210 215 220
atc ttc tcg gcc ctg gcc gcg gca cgc ggc atc tgc atc gcg cac gag 720
Ile Phe Ser Ala Leu Ala Ala Ala Arg Gly Ile Cys Ile Ala His Glu
225 230 235 240
ggc ctg gtg ccg ctg ccc cgt gcc gat gac tcg cgg ctg ggg aag gtg 768
Gly Leu Val Pro Leu Pro Arg Ala Asp Asp Ser Arg Leu Gly Lys Val
245 250 255
cag gac gtc ctg cac cag gtg aac cag agc agc gtg cag gtg gtg ctg 816
Gln Asp Val Leu His Gln Val Asn Gln Ser Ser Val Gln Val Val Leu
260 265 270
ctg ttc gcc tcc gtg cac gcc gcc cac gcc ctc ttc aac tac agc atc 864
Leu Phe Ala Ser Val His Ala Ala His Ala Leu Phe Asn Tyr Ser Ile
275 280 285
agc agc agg ctc tcg ccc aag gtg tgg gtg gcc agc gag gcc tgg ctg 912
Ser Ser Arg Leu Ser Pro Lys Val Trp Val Ala Ser Glu Ala Trp Leu
290 295 300
acc tct gac ctg gtc atg ggg ctg ccc ggc atg gcc cag atg ggc acg 960
Thr Ser Asp Leu Val Met Gly Leu Pro Gly Met Ala Gln Met Gly Thr
305 310 315 320
gtg ctt ggc ttc ctc cag agg ggt gcc cag ctg cac gag ttc ccc cag 1008
Val Leu Gly Phe Leu Gln Arg Gly Ala Gln Leu His Glu Phe Pro Gln
325 330 335
tac gtg aag acg cac ctg gcc ctg gcc acc gac ccg gcc ttc tgc tct 1056
Tyr Val Lys Thr His Leu Ala Leu Ala Thr Asp Pro Ala Phe Cys Ser
340 345 350
gcc ctg ggc gag agg gag cag ggt ctg gag gag gac gtg gtg ggc cag 1104
Ala Leu Gly Glu Arg Glu Gln Gly Leu Glu Glu Asp Val Val Gly Gln
355 360 365
cgc tgc ccg cag tgt gac tgc atc acg ctg cag aac gtg agc gca ggg 1152
Arg Cys Pro Gln Cys Asp Cys Ile Thr Leu Gln Asn Val Ser Ala Gly
370 375 380
cta aat cac cac cag acg ttc tct gtc tac gca gct gtg tat agc gtg 1200
Leu Asn His His Gln Thr Phe Ser Val Tyr Ala Ala Val Tyr Ser Val
385 390 395 400
gcc cag gcc ctg cac aac act ctt cag tgc aac gcc tca ggc tgc ccc 1248
Ala Gln Ala Leu His Asn Thr Leu Gln Cys Asn Ala Ser Gly Cys Pro
405 410 415
gcg cag gac ccc gtg aag ccc tgg cag ctc ctg gag aac atg tac aac 1296
Ala Gln Asp Pro Val Lys Pro Trp Gln Leu Leu Glu Asn Met Tyr Asn
420 425 430
ctg acc ttc cac gtg ggc ggg ctg ccg ctg cgg ttc gac agc agc gga 1344
Leu Thr Phe His Val Gly Gly Leu Pro Leu Arg Phe Asp Ser Ser Gly
435 440 445
aac gtg gac atg gag tac gac ctg aag ctg tgg gtg tgg cag ggc tca 1392
Asn Val Asp Met Glu Tyr Asp Leu Lys Leu Trp Val Trp Gln Gly Ser
450 455 460
gtg ccc agg ctc cac gac gtg ggc agg ttc aac ggc agc ctc agg aca 1440
Val Pro Arg Leu His Asp Val Gly Arg Phe Asn Gly Ser Leu Arg Thr
465 470 475 480
gag cgc ctg aag atc cgc tgg cac acg tct gac aac cag aag ccc gtg 1488
Glu Arg Leu Lys Ile Arg Trp His Thr Ser Asp Asn Gln Lys Pro Val
485 490 495
tcc cgg tgc tcg cgg cag tgc cag gag ggc cag gtg cgc cgg gtc aag 1536
Ser Arg Cys Ser Arg Gln Cys Gln Glu Gly Gln Val Arg Arg Val Lys
500 505 510
ggg ttc cac tcc tgc tgc tac gac tgt gtg gac tgc gag gcg ggc agc 1584
Gly Phe His Ser Cys Cys Tyr Asp Cys Val Asp Cys Glu Ala Gly Ser
515 520 525
tac cgg caa aac cca gac gac atc gcc tgc acc ttt tgt ggc cag gat 1632
Tyr Arg Gln Asn Pro Asp Asp Ile Ala Cys Thr Phe Cys Gly Gln Asp
530 535 540
gag tgg tcc ccg gag cga agc aca cgc tgc ttc cgc cgc agg tct cgg 1680
Glu Trp Ser Pro Glu Arg Ser Thr Arg Cys Phe Arg Arg Arg Ser Arg
545 550 555 560
ttc ctg gca tgg ggc gag ccg gct gtg ctg ctg ctg ctc ctg ctg ctg 1728
Phe Leu Ala Trp Gly Glu Pro Ala Val Leu Leu Leu Leu Leu Leu Leu
565 570 575
agc ctg gcg ctg ggc ctt gtg ctg gct gct ttg ggg ctg ttc gtt cac 1776
Ser Leu Ala Leu Gly Leu Val Leu Ala Ala Leu Gly Leu Phe Val His
580 585 590
cat cgg gac agc cca ctg gtt cag gcc tcg ggg ggg ccc ctg gcc tgc 1824
His Arg Asp Ser Pro Leu Val Gln Ala Ser Gly Gly Pro Leu Ala Cys
595 600 605
ttt ggc ctg gtg tgc ctg ggc ctg gtc tgc ctc agc gtc ctc ctg ttc 1872
Phe Gly Leu Val Cys Leu Gly Leu Val Cys Leu Ser Val Leu Leu Phe
610 615 620
cct ggc cag ccc agc cct gcc cga tgc ctg gcc cag cag ccc ttg tcc 1920
Pro Gly Gln Pro Ser Pro Ala Arg Cys Leu Ala Gln Gln Pro Leu Ser
625 630 635 640
cac ctc ccg ctc acg ggc tgc ctg agc aca ctc ttc ctg cag gcg gcc 1968
His Leu Pro Leu Thr Gly Cys Leu Ser Thr Leu Phe Leu Gln Ala Ala
645 650 655
gag atc ttc gtg gag tca gaa ctg cct ctg agc tgg gca gac cgg ctg 2016
Glu Ile Phe Val Glu Ser Glu Leu Pro Leu Ser Trp Ala Asp Arg Leu
660 665 670
agt ggc tgc ctg cgg ggg ccc tgg gcc tgg ctg gtg gtg ctg ctg gcc 2064
Ser Gly Cys Leu Arg Gly Pro Trp Ala Trp Leu Val Val Leu Leu Ala
675 680 685
atg ctg gtg gag gtc gca ctg tgc acc tgg tac ctg gtg gcc ttc ccg 2112
Met Leu Val Glu Val Ala Leu Cys Thr Trp Tyr Leu Val Ala Phe Pro
690 695 700
ccg gag gtg gtg acg gac tgg cac atg ctg ccc acg gag gcg ctg gtg 2160
Pro Glu Val Val Thr Asp Trp His Met Leu Pro Thr Glu Ala Leu Val
705 710 715 720
cac tgc cgc aca cgc tcc tgg gtc agc ttc ggc cta gcg cac gcc acc 2208
His Cys Arg Thr Arg Ser Trp Val Ser Phe Gly Leu Ala His Ala Thr
725 730 735
aat gcc acg ctg gcc ttt ctc tgc ttc ctg ggc act ttc ctg gtg cgg 2256
Asn Ala Thr Leu Ala Phe Leu Cys Phe Leu Gly Thr Phe Leu Val Arg
740 745 750
agc cag ccg ggc cgc tac aac cgt gcc cgt ggc ctc acc ttt gcc atg 2304
Ser Gln Pro Gly Arg Tyr Asn Arg Ala Arg Gly Leu Thr Phe Ala Met
755 760 765
ctg gcc tac ttc atc acc tgg gtc tcc ttt gtg ccc ctc ctg gcc aat 2352
Leu Ala Tyr Phe Ile Thr Trp Val Ser Phe Val Pro Leu Leu Ala Asn
770 775 780
gtg cag gtg gtc ctc agg ccc gcc gtg cag atg ggc gcc ctc ctg ctc 2400
Val Gln Val Val Leu Arg Pro Ala Val Gln Met Gly Ala Leu Leu Leu
785 790 795 800
tgt gtc ctg ggc atc ctg gct gcc ttc cac ctg ccc agg tgt tac ctg 2448
Cys Val Leu Gly Ile Leu Ala Ala Phe His Leu Pro Arg Cys Tyr Leu
805 810 815
ctc atg cgg cag cca ggg ctc aac acc ccc gag ttc ttc ctg gga ggg 2496
Leu Met Arg Gln Pro Gly Leu Asn Thr Pro Glu Phe Phe Leu Gly Gly
820 825 830
ggc cct ggg gat gcc caa ggc cag aat gac ggg aac aca gga aat cag 2544
Gly Pro Gly Asp Ala Gln Gly Gln Asn Asp Gly Asn Thr Gly Asn Gln
835 840 845
ggg aaa cat gag tga 2559
Gly Lys His Glu
850
<210> 64
<211> 852
<212> PRT
<213> 智人
<400> 64
Met Leu Gly Pro Ala Val Leu Gly Leu Ser Leu Trp Ala Leu Leu His
1 5 10 15
Pro Gly Thr Gly Ala Pro Leu Cys Leu Ser Gln Gln Leu Arg Met Lys
20 25 30
Gly Asp Tyr Val Leu Gly Gly Leu Phe Pro Leu Gly Glu Ala Glu Glu
35 40 45
Ala Gly Leu Arg Ser Arg Thr Arg Pro Ser Ser Pro Val Cys Thr Arg
50 55 60
Phe Ser Ser Asn Gly Leu Leu Trp Ala Leu Ala Met Lys Met Ala Val
65 70 75 80
Glu Glu Ile Asn Asn Lys Ser Asp Leu Leu Pro Gly Leu Arg Leu Gly
85 90 95
Tyr Asp Leu Phe Asp Thr Cys Ser Glu Pro Val Val Ala Met Lys Pro
100 105 110
Ser Leu Met Phe Leu Ala Lys Ala Gly Ser Arg Asp Ile Ala Ala Tyr
115 120 125
Cys Asn Tyr Thr Gln Tyr Gln Pro Arg Val Leu Ala Val Ile Gly Pro
130 135 140
His Ser Ser Glu Leu Ala Met Val Thr Gly Lys Phe Phe Ser Phe Phe
145 150 155 160
Leu Met Pro Gln Val Ser Tyr Gly Ala Ser Met Glu Leu Leu Ser Ala
165 170 175
Arg Glu Thr Phe Pro Ser Phe Phe Arg Thr Val Pro Ser Asp Arg Val
180 185 190
Gln Leu Thr Ala Ala Ala Glu Leu Leu Gln Glu Phe Gly Trp Asn Trp
195 200 205
Val Ala Ala Leu Gly Ser Asp Asp Glu Tyr Gly Arg Gln Gly Leu Ser
210 215 220
Ile Phe Ser Ala Leu Ala Ala Ala Arg Gly Ile Cys Ile Ala His Glu
225 230 235 240
Gly Leu Val Pro Leu Pro Arg Ala Asp Asp Ser Arg Leu Gly Lys Val
245 250 255
Gln Asp Val Leu His Gln Val Asn Gln Ser Ser Val Gln Val Val Leu
260 265 270
Leu Phe Ala Ser Val His Ala Ala His Ala Leu Phe Asn Tyr Ser Ile
275 280 285
Ser Ser Arg Leu Ser Pro Lys Val Trp Val Ala Ser Glu Ala Trp Leu
290 295 300
Thr Ser Asp Leu Val Met Gly Leu Pro Gly Met Ala Gln Met Gly Thr
305 310 315 320
Val Leu Gly Phe Leu Gln Arg Gly Ala Gln Leu His Glu Phe Pro Gln
325 330 335
Tyr Val Lys Thr His Leu Ala Leu Ala Thr Asp Pro Ala Phe Cys Ser
340 345 350
Ala Leu Gly Glu Arg Glu Gln Gly Leu Glu Glu Asp Val Val Gly Gln
355 360 365
Arg Cys Pro Gln Cys Asp Cys Ile Thr Leu Gln Asn Val Ser Ala Gly
370 375 380
Leu Asn His His Gln Thr Phe Ser Val Tyr Ala Ala Val Tyr Ser Val
385 390 395 400
Ala Gln Ala Leu His Asn Thr Leu Gln Cys Asn Ala Ser Gly Cys Pro
405 410 415
Ala Gln Asp Pro Val Lys Pro Trp Gln Leu Leu Glu Asn Met Tyr Asn
420 425 430
Leu Thr Phe His Val Gly Gly Leu Pro Leu Arg Phe Asp Ser Ser Gly
435 440 445
Asn Val Asp Met Glu Tyr Asp Leu Lys Leu Trp Val Trp Gln Gly Ser
450 455 460
Val Pro Arg Leu His Asp Val Gly Arg Phe Asn Gly Ser Leu Arg Thr
465 470 475 480
Glu Arg Leu Lys Ile Arg Trp His Thr Ser Asp Asn Gln Lys Pro Val
485 490 495
Ser Arg Cys Ser Arg Gln Cys Gln Glu Gly Gln Val Arg Arg Val Lys
500 505 510
Gly Phe His Ser Cys Cys Tyr Asp Cys Val Asp Cys Glu Ala Gly Ser
515 520 525
Tyr Arg Gln Asn Pro Asp Asp Ile Ala Cys Thr Phe Cys Gly Gln Asp
530 535 540
Glu Trp Ser Pro Glu Arg Ser Thr Arg Cys Phe Arg Arg Arg Ser Arg
545 550 555 560
Phe Leu Ala Trp Gly Glu Pro Ala Val Leu Leu Leu Leu Leu Leu Leu
565 570 575
Ser Leu Ala Leu Gly Leu Val Leu Ala Ala Leu Gly Leu Phe Val His
580 585 590
His Arg Asp Ser Pro Leu Val Gln Ala Ser Gly Gly Pro Leu Ala Cys
595 600 605
Phe Gly Leu Val Cys Leu Gly Leu Val Cys Leu Ser Val Leu Leu Phe
610 615 620
Pro Gly Gln Pro Ser Pro Ala Arg Cys Leu Ala Gln Gln Pro Leu Ser
625 630 635 640
His Leu Pro Leu Thr Gly Cys Leu Ser Thr Leu Phe Leu Gln Ala Ala
645 650 655
Glu Ile Phe Val Glu Ser Glu Leu Pro Leu Ser Trp Ala Asp Arg Leu
660 665 670
Ser Gly Cys Leu Arg Gly Pro Trp Ala Trp Leu Val Val Leu Leu Ala
675 680 685
Met Leu Val Glu Val Ala Leu Cys Thr Trp Tyr Leu Val Ala Phe Pro
690 695 700
Pro Glu Val Val Thr Asp Trp His Met Leu Pro Thr Glu Ala Leu Val
705 710 715 720
His Cys Arg Thr Arg Ser Trp Val Ser Phe Gly Leu Ala His Ala Thr
725 730 735
Asn Ala Thr Leu Ala Phe Leu Cys Phe Leu Gly Thr Phe Leu Val Arg
740 745 750
Ser Gln Pro Gly Arg Tyr Asn Arg Ala Arg Gly Leu Thr Phe Ala Met
755 760 765
Leu Ala Tyr Phe Ile Thr Trp Val Ser Phe Val Pro Leu Leu Ala Asn
770 775 780
Val Gln Val Val Leu Arg Pro Ala Val Gln Met Gly Ala Leu Leu Leu
785 790 795 800
Cys Val Leu Gly Ile Leu Ala Ala Phe His Leu Pro Arg Cys Tyr Leu
805 810 815
Leu Met Arg Gln Pro Gly Leu Asn Thr Pro Glu Phe Phe Leu Gly Gly
820 825 830
Gly Pro Gly Asp Ala Gln Gly Gln Asn Asp Gly Asn Thr Gly Asn Gln
835 840 845
Gly Lys His Glu
850
<210> 65
<211> 1125
<212> DNA
<213> 智人
<220>
<221> CDS
<222> (1)..(1125)
<400> 65
atg gcc cgc tcg ctg acc tgg cgc tgc tgc ccc tgg tgc ctg acg gag 48
Met Ala Arg Ser Leu Thr Trp Arg Cys Cys Pro Trp Cys Leu Thr Glu
1 5 10 15
gat gag aag gcc gcc gcc cgg gtg gac cag gag atc aac agg atc ctc 96
Asp Glu Lys Ala Ala Ala Arg Val Asp Gln Glu Ile Asn Arg Ile Leu
20 25 30
ttg gag cag aag aag cag gac cgc ggg gag ctg aag ctg ctg ctt ttg 144
Leu Glu Gln Lys Lys Gln Asp Arg Gly Glu Leu Lys Leu Leu Leu Leu
35 40 45
ggc cca ggc gag agc ggg aag agc acc ttc atc aag cag atg cgg atc 192
Gly Pro Gly Glu Ser Gly Lys Ser Thr Phe Ile Lys Gln Met Arg Ile
50 55 60
atc cac ggc gcc ggc tac tcg gag gag gag cgc aag ggc ttc cgg ccc 240
Ile His Gly Ala Gly Tyr Ser Glu Glu Glu Arg Lys Gly Phe Arg Pro
65 70 75 80
ctg gtc tac cag aac atc ttc gtg tcc atg cgg gcc atg atc gag gcc 288
Leu Val Tyr Gln Asn Ile Phe Val Ser Met Arg Ala Met Ile Glu Ala
85 90 95
atg gag cgg ctg cag att cca ttc agc agg ccc gag agc aag cac cac 336
Met Glu Arg Leu Gln Ile Pro Phe Ser Arg Pro Glu Ser Lys His His
100 105 110
gct agc ctg gtc atg agc cag gac ccc tat aaa gtg acc acg ttt gag 384
Ala Ser Leu Val Met Ser Gln Asp Pro Tyr Lys Val Thr Thr Phe Glu
115 120 125
aag cgc tac gct gcg gcc atg cag tgg ctg tgg agg gat gcc ggc atc 432
Lys Arg Tyr Ala Ala Ala Met Gln Trp Leu Trp Arg Asp Ala Gly Ile
130 135 140
cgg gcc tgc tat gag cgt cgg cgg gaa ttc cac ctg ctc gat tca gcc 480
Arg Ala Cys Tyr Glu Arg Arg Arg Glu Phe His Leu Leu Asp Ser Ala
145 150 155 160
gtg tac tac ctg tcc cac ctg gag cgc atc acc gag gag ggc tac gtc 528
Val Tyr Tyr Leu Ser His Leu Glu Arg Ile Thr Glu Glu Gly Tyr Val
165 170 175
ccc aca gct cag gac gtg ctc cgc agc cgc atg ccc acc act ggc atc 576
Pro Thr Ala Gln Asp Val Leu Arg Ser Arg Met Pro Thr Thr Gly Ile
180 185 190
aac gag tac tgc ttc tcc gtg cag aaa acc aac ctg cgg atc gtg gac 624
Asn Glu Tyr Cys Phe Ser Val Gln Lys Thr Asn Leu Arg Ile Val Asp
195 200 205
gtc ggg ggc cag aag tca gag cgt aag aaa tgg atc cat tgt ttc gag 672
Val Gly Gly Gln Lys Ser Glu Arg Lys Lys Trp Ile His Cys Phe Glu
210 215 220
aac gtg atc gcc ctc atc tac ctg gcc tca ctg agt gaa tac gac cag 720
Asn Val Ile Ala Leu Ile Tyr Leu Ala Ser Leu Ser Glu Tyr Asp Gln
225 230 235 240
tgc ctg gag gag aac aac cag gag aac cgc atg aag gag agc ctc gca 768
Cys Leu Glu Glu Asn Asn Gln Glu Asn Arg Met Lys Glu Ser Leu Ala
245 250 255
ttg ttt ggg act atc ctg gaa cta ccc tgg ttc aaa agc aca tcc gtc 816
Leu Phe Gly Thr Ile Leu Glu Leu Pro Trp Phe Lys Ser Thr Ser Val
260 265 270
atc ctc ttt ctc aac aaa acc gac atc ctg gag gag aaa atc ccc acc 864
Ile Leu Phe Leu Asn Lys Thr Asp Ile Leu Glu Glu Lys Ile Pro Thr
275 280 285
tcc cac ctg gct acc tat ttc ccc agt ttc cag ggc cct aag cag gat 912
Ser His Leu Ala Thr Tyr Phe Pro Ser Phe Gln Gly Pro Lys Gln Asp
290 295 300
gct gag gca gcc aag agg ttc atc ctg gac atg tac acg agg atg tac 960
Ala Glu Ala Ala Lys Arg Phe Ile Leu Asp Met Tyr Thr Arg Met Tyr
305 310 315 320
acc ggg tgc gtg gac ggc ccc gag ggc agc aag aag ggc gca cga tcc 1008
Thr Gly Cys Val Asp Gly Pro Glu Gly Ser Lys Lys Gly Ala Arg Ser
325 330 335
cga cgc ctt ttc agc cac tac aca tgt gcc aca gac aca cag aac atc 1056
Arg Arg Leu Phe Ser His Tyr Thr Cys Ala Thr Asp Thr Gln Asn Ile
340 345 350
cgc aag gtc ttc aag gac gtg cgg gac tcg gtg ctc gcc cgc tac ctg 1104
Arg Lys Val Phe Lys Asp Val Arg Asp Ser Val Leu Ala Arg Tyr Leu
355 360 365
gac gag atc aac ctg ctg tga 1125
Asp Glu Ile Asn Leu Leu
370
<210> 66
<211> 374
<212> PRT
<213> 智人
<400> 66
Met Ala Arg Ser Leu Thr Trp Arg Cys Cys Pro Trp Cys Leu Thr Glu
1 5 10 15
Asp Glu Lys Ala Ala Ala Arg Val Asp Gln Glu Ile Asn Arg Ile Leu
20 25 30
Leu Glu Gln Lys Lys Gln Asp Arg Gly Glu Leu Lys Leu Leu Leu Leu
35 40 45
Gly Pro Gly Glu Ser Gly Lys Ser Thr Phe Ile Lys Gln Met Arg Ile
50 55 60
Ile His Gly Ala Gly Tyr Ser Glu Glu Glu Arg Lys Gly Phe Arg Pro
65 70 75 80
Leu Val Tyr Gln Asn Ile Phe Val Ser Met Arg Ala Met Ile Glu Ala
85 90 95
Met Glu Arg Leu Gln Ile Pro Phe Ser Arg Pro Glu Ser Lys His His
100 105 110
Ala Ser Leu Val Met Ser Gln Asp Pro Tyr Lys Val Thr Thr Phe Glu
115 120 125
Lys Arg Tyr Ala Ala Ala Met Gln Trp Leu Trp Arg Asp Ala Gly Ile
130 135 140
Arg Ala Cys Tyr Glu Arg Arg Arg Glu Phe His Leu Leu Asp Ser Ala
145 150 155 160
Val Tyr Tyr Leu Ser His Leu Glu Arg Ile Thr Glu Glu Gly Tyr Val
165 170 175
Pro Thr Ala Gln Asp Val Leu Arg Ser Arg Met Pro Thr Thr Gly Ile
180 185 190
Asn Glu Tyr Cys Phe Ser Val Gln Lys Thr Asn Leu Arg Ile Val Asp
195 200 205
Val Gly Gly Gln Lys Ser Glu Arg Lys Lys Trp Ile His Cys Phe Glu
210 215 220
Asn Val Ile Ala Leu Ile Tyr Leu Ala Ser Leu Ser Glu Tyr Asp Gln
225 230 235 240
Cys Leu Glu Glu Asn Asn Gln Glu Asn Arg Met Lys Glu Ser Leu Ala
245 250 255
Leu Phe Gly Thr Ile Leu Glu Leu Pro Trp Phe Lys Ser Thr Ser Val
260 265 270
Ile Leu Phe Leu Asn Lys Thr Asp Ile Leu Glu Glu Lys Ile Pro Thr
275 280 285
Ser His Leu Ala Thr Tyr Phe Pro Ser Phe Gln Gly Pro Lys Gln Asp
290 295 300
Ala Glu Ala Ala Lys Arg Phe Ile Leu Asp Met Tyr Thr Arg Met Tyr
305 310 315 320
Thr Gly Cys Val Asp Gly Pro Glu Gly Ser Lys Lys Gly Ala Arg Ser
325 330 335
Arg Arg Leu Phe Ser His Tyr Thr Cys Ala Thr Asp Thr Gln Asn Ile
340 345 350
Arg Lys Val Phe Lys Asp Val Arg Asp Ser Val Leu Ala Arg Tyr Leu
355 360 365
Asp Glu Ile Asn Leu Leu
370
<210> 67
<211> 1065
<212> DNA
<213> 褐家鼠(Rattus norvegicus)
<220>
<221> CDS
<222> (1)..(1065)
<400> 67
atg gga agt gga att agt tca gag agc aag gag tca gcc aaa agg tcc 48
Met Gly Ser Gly Ile Ser Ser Glu Ser Lys Glu Ser Ala Lys Arg Ser
1 5 10 15
aaa gaa ctg gag aag aag ctt cag gaa gat gct gaa cga gat gca aga 96
Lys Glu Leu Glu Lys Lys Leu Gln Glu Asp Ala Glu Arg Asp Ala Arg
20 25 30
act gtg aag ttg ctg cta tta gga gca ggt gaa tct gga aaa agt act 144
Thr Val Lys Leu Leu Leu Leu Gly Ala Gly Glu Ser Gly Lys Ser Thr
35 40 45
att gtt aaa caa atg aag atc atc cac aag aat ggt tac agt aaa caa 192
Ile Val Lys Gln Met Lys Ile Ile His Lys Asn Gly Tyr Ser Lys Gln
50 55 60
gaa tgc atg gag ttt aaa gca gtg gtt tac agt aac acg ttg cag tcc 240
Glu Cys Met Glu Phe Lys Ala Val Val Tyr Ser Asn Thr Leu Gln Ser
65 70 75 80
atc ctg gcc att gtg aaa gcc atg act aca cta ggg att gat tat gtc 288
Ile Leu Ala Ile Val Lys Ala Met Thr Thr Leu Gly Ile Asp Tyr Val
85 90 95
aat ccg aga agt aga gag gac caa caa ctg ctt ctc tcc atg gca aac 336
Asn Pro Arg Ser Arg Glu Asp Gln Gln Leu Leu Leu Ser Met Ala Asn
100 105 110
aca cta gaa gat ggt gac atg acg cct cag ttg gct gaa ata att aaa 384
Thr Leu Glu Asp Gly Asp Met Thr Pro Gln Leu Ala Glu Ile Ile Lys
115 120 125
cgt ctg tgg ggc gat cca gga att caa gcc tgc ttc gaa agg gca tct 432
Arg Leu Trp Gly Asp Pro Gly Ile Gln Ala Cys Phe Glu Arg Ala Ser
130 135 140
gaa tac cag ctc aat gac tct gca gct tac tac ctt aat gac tta gat 480
Glu Tyr Gln Leu Asn Asp Ser Ala Ala Tyr Tyr Leu Asn Asp Leu Asp
145 150 155 160
aga ctc aca gcc cct ggg tat gtg cca aat gaa caa gac gtt cta cat 528
Arg Leu Thr Ala Pro Gly Tyr Val Pro Asn Glu Gln Asp Val Leu His
165 170 175
tcc cgg gtg aaa acc act ggt atc att gaa act caa ttc tcc ttt aaa 576
Ser Arg Val Lys Thr Thr Gly Ile Ile Glu Thr Gln Phe Ser Phe Lys
180 185 190
gac ttg aac ttc aga atg ttt gat gta ggt ggc cag aga tca gaa aga 624
Asp Leu Asn Phe Arg Met Phe Asp Val Gly Gly Gln Arg Ser Glu Arg
195 200 205
aag aaa tgg atc cac tgc ttt gaa gga gtg acg tgc att ata ttt tgt 672
Lys Lys Trp Ile His Cys Phe Glu Gly Val Thr Cys Ile Ile Phe Cys
210 215 220
gca gcc cta agt gcc tac gac atg gta ctt gta gaa gat gaa gag gtg 720
Ala Ala Leu Ser Ala Tyr Asp Met Val Leu Val Glu Asp Glu Glu Val
225 230 235 240
aac aga atg cat gaa agt ctt cac ctc ttc aac agc atc tgt aat cac 768
Asn Arg Met His Glu Ser Leu His Leu Phe Asn Ser Ile Cys Asn His
245 250 255
aag tat ttt gca acc acc tcc att gtt ctg ttt ctt aac aag aaa gat 816
Lys Tyr Phe Ala Thr Thr Ser Ile Val Leu Phe Leu Asn Lys Lys Asp
260 265 270
ctc ttc cag gag aaa gtg acc aag gtg cac ctc agc atc tgt ttc cca 864
Leu Phe Gln Glu Lys Val Thr Lys Val His Leu Ser Ile Cys Phe Pro
275 280 285
gaa tac act gga cca aat aca ttc gaa gat gca ggg aac tac atc aag 912
Glu Tyr Thr Gly Pro Asn Thr Phe Glu Asp Ala Gly Asn Tyr Ile Lys
290 295 300
aac cag ttc cta gac ctg aac tta aaa aaa gaa gat aag gaa atc tat 960
Asn Gln Phe Leu Asp Leu Asn Leu Lys Lys Glu Asp Lys Glu Ile Tyr
305 310 315 320
tct cac atg acc tgc gct act gac aca caa aac gtc aaa ttc gtg ttt 1008
Ser His Met Thr Cys Ala Thr Asp Thr Gln Asn Val Lys Phe Val Phe
325 330 335
gat gcc gtg aca gat ata ata ata aaa gag aac ctc aaa gac tgt ggg 1056
Asp Ala Val Thr Asp Ile Ile Ile Lys Glu Asn Leu Lys Asp Cys Gly
340 345 350
ctc ttc tga 1065
Leu Phe
<210> 68
<211> 354
<212> PRT
<213> 褐家鼠(Rattus norvegicus)
<400> 68
Met Gly Ser Gly Ile Ser Ser Glu Ser Lys Glu Ser Ala Lys Arg Ser
1 5 10 15
Lys Glu Leu Glu Lys Lys Leu Gln Glu Asp Ala Glu Arg Asp Ala Arg
20 25 30
Thr Val Lys Leu Leu Leu Leu Gly Ala Gly Glu Ser Gly Lys Ser Thr
35 40 45
Ile Val Lys Gln Met Lys Ile Ile His Lys Asn Gly Tyr Ser Lys Gln
50 55 60
Glu Cys Met Glu Phe Lys Ala Val Val Tyr Ser Asn Thr Leu Gln Ser
65 70 75 80
Ile Leu Ala Ile Val Lys Ala Met Thr Thr Leu Gly Ile Asp Tyr Val
85 90 95
Asn Pro Arg Ser Arg Glu Asp Gln Gln Leu Leu Leu Ser Met Ala Asn
100 105 110
Thr Leu Glu Asp Gly Asp Met Thr Pro Gln Leu Ala Glu Ile Ile Lys
115 120 125
Arg Leu Trp Gly Asp Pro Gly Ile Gln Ala Cys Phe Glu Arg Ala Ser
130 135 140
Glu Tyr Gln Leu Asn Asp Ser Ala Ala Tyr Tyr Leu Asn Asp Leu Asp
145 150 155 160
Arg Leu Thr Ala Pro Gly Tyr Val Pro Asn Glu Gln Asp Val Leu His
165 170 175
Ser Arg Val Lys Thr Thr Gly Ile Ile Glu Thr Gln Phe Ser Phe Lys
180 185 190
Asp Leu Asn Phe Arg Met Phe Asp Val Gly Gly Gln Arg Ser Glu Arg
195 200 205
Lys Lys Trp Ile His Cys Phe Glu Gly Val Thr Cys Ile Ile Phe Cys
210 215 220
Ala Ala Leu Ser Ala Tyr Asp Met Val Leu Val Glu Asp Glu Glu Val
225 230 235 240
Asn Arg Met His Glu Ser Leu His Leu Phe Asn Ser Ile Cys Asn His
245 250 255
Lys Tyr Phe Ala Thr Thr Ser Ile Val Leu Phe Leu Asn Lys Lys Asp
260 265 270
Leu Phe Gln Glu Lys Val Thr Lys Val His Leu Ser Ile Cys Phe Pro
275 280 285
Glu Tyr Thr Gly Pro Asn Thr Phe Glu Asp Ala Gly Asn Tyr Ile Lys
290 295 300
Asn Gln Phe Leu Asp Leu Asn Leu Lys Lys Glu Asp Lys Glu Ile Tyr
305 310 315 320
Ser His Met Thr Cys Ala Thr Asp Thr Gln Asn Val Lys Phe Val Phe
325 330 335
Asp Ala Val Thr Asp Ile Ile Ile Lys Glu Asn Leu Lys Asp Cys Gly
340 345 350
Leu Phe
<210> 69
<211> 1146
<212> DNA
<213> 智人
<220>
<221> CDS
<222> (1)..(1146)
<400> 69
atg ggg tgt ttg ggc ggc aac agc aag acg acg gaa gac cag ggc gtc 48
Met Gly Cys Leu Gly Gly Asn Ser Lys Thr Thr Glu Asp Gln Gly Val
1 5 10 15
gat gaa aaa gaa cga cgc gag gcc aac aaa aag atc gag aag cag ttg 96
Asp Glu Lys Glu Arg Arg Glu Ala Asn Lys Lys Ile Glu Lys Gln Leu
20 25 30
cag aaa gag cgc ctg gct tac aag gct acc cac cgc ctg ctg ctc ctg 144
Gln Lys Glu Arg Leu Ala Tyr Lys Ala Thr His Arg Leu Leu Leu Leu
35 40 45
ggg gct ggt gag tct ggg aaa agc act atc gtc aaa cag atg agg atc 192
Gly Ala Gly Glu Ser Gly Lys Ser Thr Ile Val Lys Gln Met Arg Ile
50 55 60
ctg cac gtc aat ggg ttt aat ccc gag gaa aag aaa cag aaa att ctg 240
Leu His Val Asn Gly Phe Asn Pro Glu Glu Lys Lys Gln Lys Ile Leu
65 70 75 80
gac atc cgg aaa aat gtt aaa gat gct atc gtg aca att gtt tca gca 288
Asp Ile Arg Lys Asn Val Lys Asp Ala Ile Val Thr Ile Val Ser Ala
85 90 95
atg agt act ata ata cct cca gtt ccg ctg gcc aac cct gaa aac caa 336
Met Ser Thr Ile Ile Pro Pro Val Pro Leu Ala Asn Pro Glu Asn Gln
100 105 110
ttt cga tca gac tac atc aag agc ata gcc cct atc act gac ttt gaa 384
Phe Arg Ser Asp Tyr Ile Lys Ser Ile Ala Pro Ile Thr Asp Phe Glu
115 120 125
tat tcc cag gaa ttc ttt gac cat gtg aaa aaa ctt tgg gac gat gaa 432
Tyr Ser Gln Glu Phe Phe Asp His Val Lys Lys Leu Trp Asp Asp Glu
130 135 140
ggc gtg aag gca tgc ttt gag aga tcc aac gaa tac cag ctg att gac 480
Gly Val Lys Ala Cys Phe Glu Arg Ser Asn Glu Tyr Gln Leu Ile Asp
145 150 155 160
tgt gca caa tac ttc ctg gaa aga atc gac agc gtc agc ttg gtt gac 528
Cys Ala Gln Tyr Phe Leu Glu Arg Ile Asp Ser Val Ser Leu Val Asp
165 170 175
tac aca ccc aca gac cag gac ctc ctc aga tgc aga gtt ctg aca tct 576
Tyr Thr Pro Thr Asp Gln Asp Leu Leu Arg Cys Arg Val Leu Thr Ser
180 185 190
ggg att ttt gag aca cga ttc caa gtg gac aaa gta aac ttc cac atg 624
Gly Ile Phe Glu Thr Arg Phe Gln Val Asp Lys Val Asn Phe His Met
195 200 205
ttt gat gtt ggt ggc cag agg gat gag agg aga aaa tgg atc cag tgc 672
Phe Asp Val Gly Gly Gln Arg Asp Glu Arg Arg Lys Trp Ile Gln Cys
210 215 220
ttt aac gat gtc aca gct atc att tac gtc gca gcc tgc agt agc tac 720
Phe Asn Asp Val Thr Ala Ile Ile Tyr Val Ala Ala Cys Ser Ser Tyr
225 230 235 240
aac atg gtg att cga gaa gat aac aac acc aac agg ctg aga gag tcc 768
Asn Met Val Ile Arg Glu Asp Asn Asn Thr Asn Arg Leu Arg Glu Ser
245 250 255
ctg gat ctt ttt gaa agc atc tgg aac aac agg tgg tta cgg acc att 816
Leu Asp Leu Phe Glu Ser Ile Trp Asn Asn Arg Trp Leu Arg Thr Ile
260 265 270
tct atc atc ttg ttc ttg aac aaa caa gat atg ctg gca gaa aaa gtc 864
Ser Ile Ile Leu Phe Leu Asn Lys Gln Asp Met Leu Ala Glu Lys Val
275 280 285
ttg gca ggg aaa tca aaa att gaa gac tat ttc cca gaa tat gca aat 912
Leu Ala Gly Lys Ser Lys Ile Glu Asp Tyr Phe Pro Glu Tyr Ala Asn
290 295 300
tat act gtt cct gaa gac gca aca cca gat gca gga gaa gat ccc aaa 960
Tyr Thr Val Pro Glu Asp Ala Thr Pro Asp Ala Gly Glu Asp Pro Lys
305 310 315 320
gtt aca aga gcc aag ttc ttt atc cgg gac ctg ttt ttg agg atc agc 1008
Val Thr Arg Ala Lys Phe Phe Ile Arg Asp Leu Phe Leu Arg Ile Ser
325 330 335
acg gcc acc ggt gac ggc aaa cat tac tgc tac ccg cac ttc acc tgc 1056
Thr Ala Thr Gly Asp Gly Lys His Tyr Cys Tyr Pro His Phe Thr Cys
340 345 350
gcc gtg gac aca gag aac atc cgc agg gtg ttc aac gac tgc cgc gac 1104
Ala Val Asp Thr Glu Asn Ile Arg Arg Val Phe Asn Asp Cys Arg Asp
355 360 365
atc atc cag cgg atg cac ctc aag cag tat gag ctc ttg tga 1146
Ile Ile Gln Arg Met His Leu Lys Gln Tyr Glu Leu Leu
370 375 380
<210> 70
<211> 381
<212> PRT
<213> 智人
<400> 70
Met Gly Cys Leu Gly Gly Asn Ser Lys Thr Thr Glu Asp Gln Gly Val
1 5 10 15
Asp Glu Lys Glu Arg Arg Glu Ala Asn Lys Lys Ile Glu Lys Gln Leu
20 25 30
Gln Lys Glu Arg Leu Ala Tyr Lys Ala Thr His Arg Leu Leu Leu Leu
35 40 45
Gly Ala Gly Glu Ser Gly Lys Ser Thr Ile Val Lys Gln Met Arg Ile
50 55 60
Leu His Val Asn Gly Phe Asn Pro Glu Glu Lys Lys Gln Lys Ile Leu
65 70 75 80
Asp Ile Arg Lys Asn Val Lys Asp Ala Ile Val Thr Ile Val Ser Ala
85 90 95
Met Ser Thr Ile Ile Pro Pro Val Pro Leu Ala Asn Pro Glu Asn Gln
100 105 110
Phe Arg Ser Asp Tyr Ile Lys Ser Ile Ala Pro Ile Thr Asp Phe Glu
115 120 125
Tyr Ser Gln Glu Phe Phe Asp His Val Lys Lys Leu Trp Asp Asp Glu
130 135 140
Gly Val Lys Ala Cys Phe Glu Arg Ser Asn Glu Tyr Gln Leu Ile Asp
145 150 155 160
Cys Ala Gln Tyr Phe Leu Glu Arg Ile Asp Ser Val Ser Leu Val Asp
165 170 175
Tyr Thr Pro Thr Asp Gln Asp Leu Leu Arg Cys Arg Val Leu Thr Ser
180 185 190
Gly Ile Phe Glu Thr Arg Phe Gln Val Asp Lys Val Asn Phe His Met
195 200 205
Phe Asp Val Gly Gly Gln Arg Asp Glu Arg Arg Lys Trp Ile Gln Cys
210 215 220
Phe Asn Asp Val Thr Ala Ile Ile Tyr Val Ala Ala Cys Ser Ser Tyr
225 230 235 240
Asn Met Val Ile Arg Glu Asp Asn Asn Thr Asn Arg Leu Arg Glu Ser
245 250 255
Leu Asp Leu Phe Glu Ser Ile Trp Asn Asn Arg Trp Leu Arg Thr Ile
260 265 270
Ser Ile Ile Leu Phe Leu Asn Lys Gln Asp Met Leu Ala Glu Lys Val
275 280 285
Leu Ala Gly Lys Ser Lys Ile Glu Asp Tyr Phe Pro Glu Tyr Ala Asn
290 295 300
Tyr Thr Val Pro Glu Asp Ala Thr Pro Asp Ala Gly Glu Asp Pro Lys
305 310 315 320
Val Thr Arg Ala Lys Phe Phe Ile Arg Asp Leu Phe Leu Arg Ile Ser
325 330 335
Thr Ala Thr Gly Asp Gly Lys His Tyr Cys Tyr Pro His Phe Thr Cys
340 345 350
Ala Val Asp Thr Glu Asn Ile Arg Arg Val Phe Asn Asp Cys Arg Asp
355 360 365
Ile Ile Gln Arg Met His Leu Lys Gln Tyr Glu Leu Leu
370 375 380
<210> 71
<211> 588
<212> DNA
<213> 脑心肌炎病毒(Encephalomyocarditis virus)
<400> 71
gcccctctcc ctcccccccc cctaacgtta ctggccgaag ccgcttggaa taaggccggt 60
gtgcgtttgt ctatatgtta ttttccacca tattgccgtc ttttggcaat gtgagggccc 120
ggaaacctgg ccctgtcttc ttgacgagca ttcctagggg tctttcccct ctcgccaaag 180
gaatgcaagg tctgttgaat gtcgtgaagg aagcagttcc tctggaagct tcttgaagac 240
aaacaacgtc tgtagcgacc ctttgcaggc agcggaaccc cccacctggc gacaggtgcc 300
tctgcggcca aaagccacgt gtataagata cacctgcaaa ggcggcacaa ccccagtgcc 360
acgttgtgag ttggatagtt gtggaaagag tcaaatggct ctcctcaagc gtattcaaca 420
aggggctgaa ggatgcccag aaggtacccc attgtatggg atctgatctg gggcctcggt 480
gcacatgctt tacatgtgtt tagtcgaggt taaaaaaacg tctaggcccc ccgaaccacg 540
gggacgtggt tttcctttga aaaacacgat gataatatgg ccacaacc 588
<210> 72
<211> 135
<212> DNA
<213> 褐家鼠(Rattus norvegicus)
<220>
<221> CDS
<222> (1)..(135)
<400> 72
atg gcc gct gtt acc tat cct tca tcc gtg cct acg acc ttg gac cct 48
Met Ala Ala Val Thr Tyr Pro Ser Ser Val Pro Thr Thr Leu Asp Pro
1 5 10 15
ggg aat gca tcc tca gcc tgg ccc ctg gac acg tcc ctg ggg aat gca 96
Gly Asn Ala Ser Ser Ala Trp Pro Leu Asp Thr Ser Leu Gly Asn Ala
20 25 30
tct gct ggc act agc ctg gca gga ctg gct gtc agt ggc 135
Ser Ala Gly Thr Ser Leu Ala Gly Leu Ala Val Ser Gly
35 40 45
<210> 73
<211> 45
<212> PRT
<213> 褐家鼠(Rattus norvegicus)
<400> 73
Met Ala Ala Val Thr Tyr Pro Ser Ser Val Pro Thr Thr Leu Asp Pro
1 5 10 15
Gly Asn Ala Ser Ser Ala Trp Pro Leu Asp Thr Ser Leu Gly Asn Ala
20 25 30
Ser Ala Gly Thr Ser Leu Ala Gly Leu Ala Val Ser Gly
35 40 45
<210> 74
<211> 1047
<212> DNA
<213> 智人
<220>
<221> CDS
<222> (1)..(1047)
<400> 74
atg aat ggc aca gaa ggc cct aac ttc tac gtg ccc ttc tcc aat gcg 48
Met Asn Gly Thr Glu Gly Pro Asn Phe Tyr Val Pro Phe Ser Asn Ala
1 5 10 15
acg ggt gtg gta cgc agc ccc ttc gag tac cca cag tac tac ctg gct 96
Thr Gly Val Val Arg Ser Pro Phe Glu Tyr Pro Gln Tyr Tyr Leu Ala
20 25 30
gag cca tgg cag ttc tcc atg ctg gcc gcc tac atg ttt ctg ctg atc 144
Glu Pro Trp Gln Phe Ser Met Leu Ala Ala Tyr Met Phe Leu Leu Ile
35 40 45
gtg ctg ggc ttc ccc atc aac ttc ctc acg ctc tac gtc acc gtc cag 192
Val Leu Gly Phe Pro Ile Asn Phe Leu Thr Leu Tyr Val Thr Val Gln
50 55 60
cac aag aag ctg cgc acg cct ctc aac tac atc ctg ctc aac cta gcc 240
His Lys Lys Leu Arg Thr Pro Leu Asn Tyr Ile Leu Leu Asn Leu Ala
65 70 75 80
gtg gct gac ctc ttc atg gtc cta ggt ggc ttc acc agc acc ctc tac 288
Val Ala Asp Leu Phe Met Val Leu Gly Gly Phe Thr Ser Thr Leu Tyr
85 90 95
acc tct ctg cat gga tac ttc gtc ttc ggg ccc aca gga tgc aat ttg 336
Thr Ser Leu His Gly Tyr Phe Val Phe Gly Pro Thr Gly Cys Asn Leu
100 105 110
gag ggc ttc ttt gcc acc ctg ggc ggt gaa att gcc ctg tgg tcc ttg 384
Glu Gly Phe Phe Ala Thr Leu Gly Gly Glu Ile Ala Leu Trp Ser Leu
115 120 125
gtg gtc ctg gcc atc gag cgg tac gtg gtg gtg tgt aag ccc atg agc 432
Val Val Leu Ala Ile Glu Arg Tyr Val Val Val Cys Lys Pro Met Ser
130 135 140
aac ttc cgc ttc ggg gag aac cat gcc atc atg ggc gtt gcc ttc acc 480
Asn Phe Arg Phe Gly Glu Asn His Ala Ile Met Gly Val Ala Phe Thr
145 150 155 160
tgg gtc atg gcg ctg gcc tgc gcc gca ccc cca ctc gcc ggc tgg tcc 528
Trp Val Met Ala Leu Ala Cys Ala Ala Pro Pro Leu Ala Gly Trp Ser
165 170 175
agg tac atc ccc gag ggc ctg cag tgc tcg tgt gga atc gac tac tac 576
Arg Tyr Ile Pro Glu Gly Leu Gln Cys Ser Cys Gly Ile Asp Tyr Tyr
180 185 190
acg ctc aag ccg gag gtc aac aac gag tct ttt gtc atc tac atg ttc 624
Thr Leu Lys Pro Glu Val Asn Asn Glu Ser Phe Val Ile Tyr Met Phe
195 200 205
gtg gtc cac ttc acc atc ccc atg att atc atc ttt ttc tgc tat ggg 672
Val Val His Phe Thr Ile Pro Met Ile Ile Ile Phe Phe Cys Tyr Gly
210 215 220
cag ctc gtc ttc acc gtc aag gag gcc gct gcc cag cag cag gag tca 720
Gln Leu Val Phe Thr Val Lys Glu Ala Ala Ala Gln Gln Gln Glu Ser
225 230 235 240
gcc acc aca cag aag gca gag aag gag gtc acc cgc atg gtc atc atc 768
Ala Thr Thr Gln Lys Ala Glu Lys Glu Val Thr Arg Met Val Ile Ile
245 250 255
atg gtc atc gct ttc ctg atc tgc tgg gtg ccc tac gcc agc gtg gca 816
Met Val Ile Ala Phe Leu Ile Cys Trp Val Pro Tyr Ala Ser Val Ala
260 265 270
ttc tac atc ttc acc cac cag ggc tcc aac ttc ggt ccc atc ttc atg 864
Phe Tyr Ile Phe Thr His Gln Gly Ser Asn Phe Gly Pro Ile Phe Met
275 280 285
acc atc cca gcg ttc ttt gcc aag agc gcc gcc atc tac aac cct gtc 912
Thr Ile Pro Ala Phe Phe Ala Lys Ser Ala Ala Ile Tyr Asn Pro Val
290 295 300
atc tat atc atg atg aac aag cag ttc cgg aac tgc atg ctc acc acc 960
Ile Tyr Ile Met Met Asn Lys Gln Phe Arg Asn Cys Met Leu Thr Thr
305 310 315 320
atc tgc tgc ggc aag aac cca ctg ggt gac gat gag gcc tct gct acc 1008
Ile Cys Cys Gly Lys Asn Pro Leu Gly Asp Asp Glu Ala Ser Ala Thr
325 330 335
gtg tcc aag acg gag acg agc cag gtg gcc ccg gcc taa 1047
Val Ser Lys Thr Glu Thr Ser Gln Val Ala Pro Ala
340 345
<210> 75
<211> 348
<212> PRT
<213> 智人
<400> 75
Met Asn Gly Thr Glu Gly Pro Asn Phe Tyr Val Pro Phe Ser Asn Ala
1 5 10 15
Thr Gly Val Val Arg Ser Pro Phe Glu Tyr Pro Gln Tyr Tyr Leu Ala
20 25 30
Glu Pro Trp Gln Phe Ser Met Leu Ala Ala Tyr Met Phe Leu Leu Ile
35 40 45
Val Leu Gly Phe Pro Ile Asn Phe Leu Thr Leu Tyr Val Thr Val Gln
50 55 60
His Lys Lys Leu Arg Thr Pro Leu Asn Tyr Ile Leu Leu Asn Leu Ala
65 70 75 80
Val Ala Asp Leu Phe Met Val Leu Gly Gly Phe Thr Ser Thr Leu Tyr
85 90 95
Thr Ser Leu His Gly Tyr Phe Val Phe Gly Pro Thr Gly Cys Asn Leu
100 105 110
Glu Gly Phe Phe Ala Thr Leu Gly Gly Glu Ile Ala Leu Trp Ser Leu
115 120 125
Val Val Leu Ala Ile Glu Arg Tyr Val Val Val Cys Lys Pro Met Ser
130 135 140
Asn Phe Arg Phe Gly Glu Asn His Ala Ile Met Gly Val Ala Phe Thr
145 150 155 160
Trp Val Met Ala Leu Ala Cys Ala Ala Pro Pro Leu Ala Gly Trp Ser
165 170 175
Arg Tyr Ile Pro Glu Gly Leu Gln Cys Ser Cys Gly Ile Asp Tyr Tyr
180 185 190
Thr Leu Lys Pro Glu Val Asn Asn Glu Ser Phe Val Ile Tyr Met Phe
195 200 205
Val Val His Phe Thr Ile Pro Met Ile Ile Ile Phe Phe Cys Tyr Gly
210 215 220
Gln Leu Val Phe Thr Val Lys Glu Ala Ala Ala Gln Gln Gln Glu Ser
225 230 235 240
Ala Thr Thr Gln Lys Ala Glu Lys Glu Val Thr Arg Met Val Ile Ile
245 250 255
Met Val Ile Ala Phe Leu Ile Cys Trp Val Pro Tyr Ala Ser Val Ala
260 265 270
Phe Tyr Ile Phe Thr His Gln Gly Ser Asn Phe Gly Pro Ile Phe Met
275 280 285
Thr Ile Pro Ala Phe Phe Ala Lys Ser Ala Ala Ile Tyr Asn Pro Val
290 295 300
Ile Tyr Ile Met Met Asn Lys Gln Phe Arg Asn Cys Met Leu Thr Thr
305 310 315 320
Ile Cys Cys Gly Lys Asn Pro Leu Gly Asp Asp Glu Ala Ser Ala Thr
325 330 335
Val Ser Lys Thr Glu Thr Ser Gln Val Ala Pro Ala
340 345
<210> 76
<211> 45
<212> DNA
<213> 人工序列
<220>
<223> V5表位
<400> 76
ggtaagccta tccctaaccc tctcctcggt ctcgattcta cgtga 45
<210> 77
<211> 1125
<212> DNA
<213> 人工序列
<220>
<223> 编码Garufa16/Garufagustducin嵌合蛋白
<400> 77
atggcccgct cgctgacctg gcgctgctgc ccctggtgcc tgacggagga tgagaaggcc 60
gccgcccggg tggaccagga gatcaacagg atcctcttgg agcagaagaa gcaggaccgc 120
ggggagctga agctgctgct tttgggccca ggcgagagcg ggaagagcac cttcatcaag 180
cagatgcgga tcatccacgg cgccggctac tcggaggagg agcgcaaggg cttccggccc 240
ctggtctacc agaacatctt cgtgtccatg cgggccatga tcgaggccat ggagcggctg 300
cagattccat tcagcaggcc cgagagcaag caccacgcta gcctggtcat gagccaggac 360
ccctataaag tgaccacgtt tgagaagcgc tacgctgcgg ccatgcagtg gctgtggagg 420
gatgccggca tccgggcctg ctatgagcgt cggcgggaat tccacctgct cgattcagcc 480
gtgtactacc tgtcccacct ggagcgcatc accgaggagg gctacgtccc cacagctcag 540
gacgtgctcc gcagccgcat gcccaccact ggcatcaacg agtactgctt ctccgtgcag 600
aaaaccaacc tgcggatcgt ggacgtcggg ggccagaagt cagagcgtaa gaaatggatc 660
cattgtttcg agaacgtgat cgccctcatc tacctggcct cactgagtga atacgaccag 720
tgcctggagg agaacaacca ggagaaccgc atgaaggaga gcctcgcatt gtttgggact 780
atcctggaac taccctggtt caaaagcaca tccgtcatcc tctttctcaa caaaaccgac 840
atcctggagg agaaaatccc cacctcccac ctggctacct atttccccag tttccagggc 900
cctaagcagg atgctgaggc agccaagagg ttcatcctgg acatgtacac gaggatgtac 960
accgggtgcg tggacggccc cgagggcagc aagttaaaaa aagaagataa ggaaatctat 1020
tctcacatga cctgcgctac tgacacacaa aacgtcaaat tcgtgtttga tgccgtgaca 1080
gatataataa taaaagagaa cctcaaagac tgtgggctct tctga 1125
<210> 78
<211> 720
<212> DNA
<213> 智人
<220>
<221> CDS
<222> (1)..(720)
<400> 78
atg gtg agc aag ggc gag gag ctg ttc acc ggg gtg gtg ccc atc ctg 48
Met Val Ser Lys Gly Glu Glu Leu Phe Thr Gly Val Val Pro Ile Leu
1 5 10 15
gtc gag ctg gac ggc gac gta aac ggc cac aag ttc agc gtg tcc ggc 96
Val Glu Leu Asp Gly Asp Val Asn Gly His Lys Phe Ser Val Ser Gly
20 25 30
gag ggc gag ggc gat gcc acc tac ggc aag ctg acc ctg aag ttc atc 144
Glu Gly Glu Gly Asp Ala Thr Tyr Gly Lys Leu Thr Leu Lys Phe Ile
35 40 45
tgc acc acc ggc aag ctg ccc gtg ccc tgg ccc acc ctc gtg acc acc 192
Cys Thr Thr Gly Lys Leu Pro Val Pro Trp Pro Thr Leu Val Thr Thr
50 55 60
ctg acc tac ggc gtg cag tgc ttc agc cgc tac ccc gac cac atg aag 240
Leu Thr Tyr Gly Val Gln Cys Phe Ser Arg Tyr Pro Asp His Met Lys
65 70 75 80
cag cac gac ttc ttc aag tcc gcc atg ccc gaa ggc tac gtc cag gag 288
Gln His Asp Phe Phe Lys Ser Ala Met Pro Glu Gly Tyr Val Gln Glu
85 90 95
cgc acc atc ttc ttc aag gac gac ggc aac tac aag acc cgc gcc gag 336
Arg Thr Ile Phe Phe Lys Asp Asp Gly Asn Tyr Lys Thr Arg Ala Glu
100 105 110
gtg aag ttc gag ggc gac acc ctg gtg aac cgc atc gag ctg aag ggc 384
Val Lys Phe Glu Gly Asp Thr Leu Val Asn Arg Ile Glu Leu Lys Gly
115 120 125
atc gac ttc aag gag gac ggc aac atc ctg ggg cac aag ctg gag tac 432
Ile Asp Phe Lys Glu Asp Gly Asn Ile Leu Gly His Lys Leu Glu Tyr
130 135 140
aac tac aac agc cac aac gtc tat atc atg gcc gac aag cag aag aac 480
Asn Tyr Asn Ser His Asn Val Tyr Ile Met Ala Asp Lys Gln Lys Asn
145 150 155 160
ggc atc aag gtg aac ttc aag atc cgc cac aac atc gag gac ggc agc 528
Gly Ile Lys Val Asn Phe Lys Ile Arg His Asn Ile Glu Asp Gly Ser
165 170 175
gtg cag ctc gcc gac cac tac cag cag aac acc ccc atc ggc gac ggc 576
Val Gln Leu Ala Asp His Tyr Gln Gln Asn Thr Pro Ile Gly Asp Gly
180 185 190
ccc gtg ctg ctg ccc gac aac cac tac ctg agc acc cag tcc gcc ctg 624
Pro Val Leu Leu Pro Asp Asn His Tyr Leu Ser Thr Gln Ser Ala Leu
195 200 205
agc aaa gac ccc aac gag aag cgc gat cac atg gtc ctg ctg gag ttc 672
Ser Lys Asp Pro Asn Glu Lys Arg Asp His Met Val Leu Leu Glu Phe
210 215 220
gtg acc gcc gcc ggg atc act ctc ggc atg gac gag ctg tac aag taa 720
Val Thr Ala Ala Gly Ile Thr Leu Gly Met Asp Glu Leu Tyr Lys
225 230 235
<210> 79
<211> 239
<212> PRT
<213> 智人
<400> 79
Met Val Ser Lys Gly Glu Glu Leu Phe Thr Gly Val Val Pro Ile Leu
1 5 10 15
Val Glu Leu Asp Gly Asp Val Asn Gly His Lys Phe Ser Val Ser Gly
20 25 30
Glu Gly Glu Gly Asp Ala Thr Tyr Gly Lys Leu Thr Leu Lys Phe Ile
35 40 45
Cys Thr Thr Gly Lys Leu Pro Val Pro Trp Pro Thr Leu Val Thr Thr
50 55 60
Leu Thr Tyr Gly Val Gln Cys Phe Ser Arg Tyr Pro Asp His Met Lys
65 70 75 80
Gln His Asp Phe Phe Lys Ser Ala Met Pro Glu Gly Tyr Val Gln Glu
85 90 95
Arg Thr Ile Phe Phe Lys Asp Asp Gly Asn Tyr Lys Thr Arg Ala Glu
100 105 110
Val Lys Phe Glu Gly Asp Thr Leu Val Asn Arg Ile Glu Leu Lys Gly
115 120 125
Ile Asp Phe Lys Glu Asp Gly Asn Ile Leu Gly His Lys Leu Glu Tyr
130 135 140
Asn Tyr Asn Ser His Asn Val Tyr Ile Met Ala Asp Lys Gln Lys Asn
145 150 155 160
Gly Ile Lys Val Asn Phe Lys Ile Arg His Asn Ile Glu Asp Gly Ser
165 170 175
Val Gln Leu Ala Asp His Tyr Gln Gln Asn Thr Pro Ile Gly Asp Gly
180 185 190
Pro Val Leu Leu Pro Asp Asn His Tyr Leu Ser Thr Gln Ser Ala Leu
195 200 205
Ser Lys Asp Pro Asn Glu Lys Arg Asp His Met Val Leu Leu Glu Phe
210 215 220
Val Thr Ala Ala Gly Ile Thr Leu Gly Met Asp Glu Leu Tyr Lys
225 230 235
<210> 80
<211> 5529
<212> DNA
<213> 人工序列
<220>
<223> pcDNA3.1 Hygro(+)
<400> 80
gacggatcgg gagatctccc gatcccctat ggtgcactct cagtacaatc tgctctgatg 60
ccgcatagtt aagccagtat ctgctccctg cttgtgtgtt ggaggtcgct gagtagtgcg 120
cgagcaaaat ttaagctaca acaaggcaag gcttgaccga caattgcatg aagaatctgc 180
ttagggttag gcgttttgcg ctgcttcgcg atgtacgggc cagatatacg cgttgacatt 240
gattattgac tagttattaa tagtaatcaa ttacggggtc attagttcat agcccatata 300
tggagttccg cgttacataa cttacggtaa atggcccgcc tggctgaccg cccaacgacc 360
cccgcccatt gacgtcaata atgacgtatg ttcccatagt aacgccaata gggactttcc 420
attgacgtca atgggtggag tatttacggt aaactgccca cttggcagta catcaagtgt 480
atcatatgcc aagtacgccc cctattgacg tcaatgacgg taaatggccc gcctggcatt 540
atgcccagta catgacctta tgggactttc ctacttggca gtacatctac gtattagtca 600
tcgctattac catggtgatg cggttttggc agtacatcaa tgggcgtgga tagcggtttg 660
actcacgggg atttccaagt ctccacccca ttgacgtcaa tgggagtttg ttttggcacc 720
aaaatcaacg ggactttcca aaatgtcgta acaactccgc cccattgacg caaatgggcg 780
gtaggcgtgt acggtgggag gtctatataa gcagagctct ctggctaact agagaaccca 840
ctgcttactg gcttatcgaa attaatacga ctcactatag ggagacccaa gctggctagc 900
gtttaaactt aagcttctcg agtctagagg gcccgtttaa acccgctgat cagcctcgac 960
tgtgccttct agttgccagc catctgttgt ttgcccctcc cccgtgcctt ccttgaccct 1020
ggaaggtgcc actcccactg tcctttccta ataaaatgag gaaattgcat cgcattgtct 1080
gagtaggtgt cattctattc tggggggtgg ggtggggcag gacagcaagg gggaggattg 1140
ggaagacaat agcaggcatg ctggggatgc ggtgggctct atggcttctg aggcggaaag 1200
aaccagctgg ggctctaggg ggtatcccca cgcgccctgt agcggcgcat taagcgcggc 1260
gggtgtggtg gttacgcgca gcgtgaccgc tacacttgcc agcgccctag cgcccgctcc 1320
tttcgctttc ttcccttcct ttctcgccac gttcgccggc tttccccgtc aagctctaaa 1380
tcgggggctc cctttagggt tccgatttag tgctttacgg cacctcgacc ccaaaaaact 1440
tgattagggt gatggttcac gtagtgggcc atcgccctga tagacggttt ttcgcccttt 1500
gacgttggag tccacgttct ttaatagtgg actcttgttc caaactggaa caacactcaa 1560
ccctatctcg gtctattctt ttgatttata agggattttg ccgatttcgg cctattggtt 1620
aaaaaatgag ctgatttaac aaaaatttaa cgcgaattaa ttctgtggaa tgtgtgtcag 1680
ttagggtgtg gaaagtcccc aggctcccca gcaggcagaa gtatgcaaag catgcatctc 1740
aattagtcag caaccaggtg tggaaagtcc ccaggctccc cagcaggcag aagtatgcaa 1800
agcatgcatc tcaattagtc agcaaccata gtcccgcccc taactccgcc catcccgccc 1860
ctaactccgc ccagttccgc ccattctccg ccccatggct gactaatttt ttttatttat 1920
gcagaggccg aggccgcctc tgcctctgag ctattccaga agtagtgagg aggctttttt 1980
ggaggcctag gcttttgcaa aaagctcccg ggagcttgta tatccatttt cggatctgat 2040
cagcacgtga tgaaaaagcc tgaactcacc gcgacgtctg tcgagaagtt tctgatcgaa 2100
aagttcgaca gcgtctccga cctgatgcag ctctcggagg gcgaagaatc tcgtgctttc 2160
agcttcgatg taggagggcg tggatatgtc ctgcgggtaa atagctgcgc cgatggtttc 2220
tacaaagatc gttatgttta tcggcacttt gcatcggccg cgctcccgat tccggaagtg 2280
cttgacattg gggaattcag cgagagcctg acctattgca tctcccgccg tgcacagggt 2340
gtcacgttgc aagacctgcc tgaaaccgaa ctgcccgctg ttctgcagcc ggtcgcggag 2400
gccatggatg cgatcgctgc ggccgatctt agccagacga gcgggttcgg cccattcgga 2460
ccgcaaggaa tcggtcaata cactacatgg cgtgatttca tatgcgcgat tgctgatccc 2520
catgtgtatc actggcaaac tgtgatggac gacaccgtca gtgcgtccgt cgcgcaggct 2580
ctcgatgagc tgatgctttg ggccgaggac tgccccgaag tccggcacct cgtgcacgcg 2640
gatttcggct ccaacaatgt cctgacggac aatggccgca taacagcggt cattgactgg 2700
agcgaggcga tgttcgggga ttcccaatac gaggtcgcca acatcttctt ctggaggccg 2760
tggttggctt gtatggagca gcagacgcgc tacttcgagc ggaggcatcc ggagcttgca 2820
ggatcgccgc ggctccgggc gtatatgctc cgcattggtc ttgaccaact ctatcagagc 2880
ttggttgacg gcaatttcga tgatgcagct tgggcgcagg gtcgatgcga cgcaatcgtc 2940
cgatccggag ccgggactgt cgggcgtaca caaatcgccc gcagaagcgc ggccgtctgg 3000
accgatggct gtgtagaagt actcgccgat agtggaaacc gacgccccag cactcgtccg 3060
agggcaaagg aatagcacgt gctacgagat ttcgattcca ccgccgcctt ctatgaaagg 3120
ttgggcttcg gaatcgtttt ccgggacgcc ggctggatga tcctccagcg cggggatctc 3180
atgctggagt tcttcgccca ccccaacttg tttattgcag cttataatgg ttacaaataa 3240
agcaatagca tcacaaattt cacaaataaa gcattttttt cactgcattc tagttgtggt 3300
ttgtccaaac tcatcaatgt atcttatcat gtctgtatac cgtcgacctc tagctagagc 3360
ttggcgtaat catggtcata gctgtttcct gtgtgaaatt gttatccgct cacaattcca 3420
cacaacatac gagccggaag cataaagtgt aaagcctggg gtgcctaatg agtgagctaa 3480
ctcacattaa ttgcgttgcg ctcactgccc gctttccagt cgggaaacct gtcgtgccag 3540
ctgcattaat gaatcggcca acgcgcgggg agaggcggtt tgcgtattgg gcgctcttcc 3600
gcttcctcgc tcactgactc gctgcgctcg gtcgttcggc tgcggcgagc ggtatcagct 3660
cactcaaagg cggtaatacg gttatccaca gaatcagggg ataacgcagg aaagaacatg 3720
tgagcaaaag gccagcaaaa ggccaggaac cgtaaaaagg ccgcgttgct ggcgtttttc 3780
cataggctcc gcccccctga cgagcatcac aaaaatcgac gctcaagtca gaggtggcga 3840
aacccgacag gactataaag ataccaggcg tttccccctg gaagctccct cgtgcgctct 3900
cctgttccga ccctgccgct taccggatac ctgtccgcct ttctcccttc gggaagcgtg 3960
gcgctttctc atagctcacg ctgtaggtat ctcagttcgg tgtaggtcgt tcgctccaag 4020
ctgggctgtg tgcacgaacc ccccgttcag cccgaccgct gcgccttatc cggtaactat 4080
cgtcttgagt ccaacccggt aagacacgac ttatcgccac tggcagcagc cactggtaac 4140
aggattagca gagcgaggta tgtaggcggt gctacagagt tcttgaagtg gtggcctaac 4200
tacggctaca ctagaagaac agtatttggt atctgcgctc tgctgaagcc agttaccttc 4260
ggaaaaagag ttggtagctc ttgatccggc aaacaaacca ccgctggtag cggttttttt 4320
gtttgcaagc agcagattac gcgcagaaaa aaaggatctc aagaagatcc tttgatcttt 4380
tctacggggt ctgacgctca gtggaacgaa aactcacgtt aagggatttt ggtcatgaga 4440
ttatcaaaaa ggatcttcac ctagatcctt ttaaattaaa aatgaagttt taaatcaatc 4500
taaagtatat atgagtaaac ttggtctgac agttaccaat gcttaatcag tgaggcacct 4560
atctcagcga tctgtctatt tcgttcatcc atagttgcct gactccccgt cgtgtagata 4620
actacgatac gggagggctt accatctggc cccagtgctg caatgatacc gcgagaccca 4680
cgctcaccgg ctccagattt atcagcaata aaccagccag ccggaagggc cgagcgcaga 4740
agtggtcctg caactttatc cgcctccatc cagtctatta attgttgccg ggaagctaga 4800
gtaagtagtt cgccagttaa tagtttgcgc aacgttgttg ccattgctac aggcatcgtg 4860
gtgtcacgct cgtcgtttgg tatggcttca ttcagctccg gttcccaacg atcaaggcga 4920
gttacatgat cccccatgtt gtgcaaaaaa gcggttagct ccttcggtcc tccgatcgtt 4980
gtcagaagta agttggccgc agtgttatca ctcatggtta tggcagcact gcataattct 5040
cttactgtca tgccatccgt aagatgcttt tctgtgactg gtgagtactc aaccaagtca 5100
ttctgagaat agtgtatgcg gcgaccgagt tgctcttgcc cggcgtcaat acgggataat 5160
accgcgccac atagcagaac tttaaaagtg ctcatcattg gaaaacgttc ttcggggcga 5220
aaactctcaa ggatcttacc gctgttgaga tccagttcga tgtaacccac tcgtgcaccc 5280
aactgatctt cagcatcttt tactttcacc agcgtttctg ggtgagcaaa aacaggaagg 5340
caaaatgccg caaaaaaggg aataagggcg acacggaaat gttgaatact catactcttc 5400
ctttttcaat attattgaag catttatcag ggttattgtc tcatgagcgg atacatattt 5460
gaatgtattt agaaaaataa acaaataggg gttccgcgca catttccccg aaaagtgcca 5520
cctgacgtc 5529
<210> 81
<211> 6069
<212> DNA
<213> 人工序列
<220>
<223> pEAK10载体
<400> 81
ggcgtaatct gctgcttgca aacaaaaaaa ccaccgctac cagcggtggt ttgtttgccg 60
gatcaagagc taccaactct ttttccgaag gtaactggct tcagcagagc gcagatacca 120
aatactgtcc ttctagtgta gccgtagtta ggccaccact tcaagaactc tgtagcaccg 180
cctacatacc tcgctctgct gaagccagtt accagtggct gctgccagtg gcgataagtc 240
gtgtcttacc gggttggact caagagatag ttaccggata aggcgcagcg gtcgggctga 300
acggggggtt cgtgcacaca gcccagcttg gagcgaacga cctacaccga actgagatac 360
ctacagcgtg agctatgaga aagcgccacg cttcccgaag ggagaaaggc ggacaggtat 420
ccggtaagcg gcagggtcgg aacaggagag cgcacgaggg agcttccagg gggaaacgcc 480
tggtatcttt atagtcctgt cgggtttcgc cacctctgac ttgagcgtcg atttttgtga 540
tgctcgtcag gggggcggag cctatggaaa aacgccagca acgcaagcta gagtttaaac 600
ttgacagatg agacaataac cctgataaat gcttcaataa tattgaaaaa ggaaaagtat 660
gagtattcaa catttccgtg tcgcccttat tccctttttt gcggcatttt gccttcctgt 720
ttttgctcac ccagaaacgc tggtgaaagt aaaagatgca gaagatcact tgggtgcgcg 780
agtgggttac atcgaactgg atctcaacag cggtaagatc cttgagagtt ttcgccccga 840
agaacgtttc ccaatgatga gcacttttaa agttctgcta tgtggcgcgg tattatcccg 900
tattgatgcc gggcaagagc aactcggtcg ccgcatacac tattctcaga atgacttggt 960
tgaatactca ccagtcacag aaaagcatct tacggatggc atgacagtaa gagaattatg 1020
cagtgctgcc ataaccatga gtgataacac tgcggccaac ttacttctga caactatcgg 1080
aggaccgaag gagctaaccg cttttttgca caacatgggg gatcatgtaa ctcgccttga 1140
tcgttgggaa ccggagctga atgaagccat accaaacgac gagcgtgaca ccacgatgcc 1200
tgtagcaatg gcaacaacgt tgcgaaaact attaactggc gaactactta ctctagcttc 1260
ccggcaacaa ctaatagact ggatggaggc ggataaagtt gcaggaccac ttctgcgctc 1320
ggcacttccg gctggctggt ttattgctga taaatcagga gccggtgagc gtgggtcacg 1380
cggtatcatt gcagcactgg ggccggatgg taagccctcc cgtatcgtag ttatctacac 1440
tacggggagt caggcaacta tggatgaacg aaatagacag atcgctgaga taggtgcctc 1500
actgattaag cattggtaag gataaatttc tggtaaggag gacacgtatg gaagtgggca 1560
agttggggaa gccgtatccg ttgctgaatc tggcatatgt gggagtataa gacgcgcagc 1620
gtcgcatcag gcattttttt ctgcgccaat gcaaaaaggc catccgtcag gatggccttt 1680
cggcataact agtgaggctc cggtgcccgt cagtgggcag agcgcacatc gcccacagtc 1740
cccgagaagt tggggggagg ggtcggcaat tgaaccggtg cctagagaag gtggcgcggg 1800
gtaaactggg aaagtgatgt cgtgtactgg ctccgccttt ttcccgaggg tgggggagaa 1860
ccgtatataa gtgcagtagt cgccgtgaac gttctttttc gcaacgggtt tgccgccaga 1920
acacaggtaa gtgccgtgtg tggttcccgc gggcctggcc tctttacggg ttatggccct 1980
tgcgtgcctt gaattacttc cacctggctg cagtacgtga ttcttgatcc cgagcttcgg 2040
gttggaagtg ggtgggagag ttcgaggcct tgcgcttaag gagccccttc gcctcgtgct 2100
tgagttgagg cctggcctgg gcgctggggc cgccgcgtgc gaatctggtg gcaccttcgc 2160
gcctgtctcg ctgctttcga taagtctcta gccatttaaa atttttgatg acctgctgcg 2220
acgctttttt tctggcaaga tagtcttgta aatgcgggcc aagacgatct gcacactggt 2280
atttcggttt ttggggccgc gggcggcgac ggggcccgtg cgtcccagcg cacatgcatg 2340
ttcggcgagg cggggcctgc gagcgcggcc accgagaatc ggacgggggt agtctcaagc 2400
tggccggcct gctctggtgc ctggcctcgc gccgccgtgt atcgccccgc cctgggcggc 2460
aaggctggga gctcaaaatg gaggacgcgg cgctcgggag agcgggcggg tgagtcaccc 2520
acacaaagga aaagggcctt tccgtcctca gccgtcgctt catgtgactc cacggagtac 2580
cgggcgccgt ccaggcacct cgattagttc tcgagctttt ggagtacgtc gtctttaggt 2640
tggggggagg ggttttatgc gatggagttt ccccacactg agtgggtgga gactgaagtt 2700
aggccagctt ggcacttgat gtaattctcc ttggaatttg ccctttttga gtttggatct 2760
tggttcattc tcaagcctca gacagtggtt caaagttttt ttcttccatt tcaggtgtcg 2820
tgaaaagctt gaattcggcg cgccgcggcc gcaggtaagc cagcccaggc ctcgccctcc 2880
agctcaaggc gggacaggtg ccctagagta gcctgcatcc agggacaggc cccagccggg 2940
tgctgacacg tccacctcca tctcttcctc aggtctgccc gggtggcatc cctgtgaccc 3000
ctccccagtg cctctcctgg tcgtggaagg tgctactcca gtgcccacca gccttgtcct 3060
aataaaatta agttgcatca ttttgtttga ctaggtgtcc ttgtataata ttatggggtg 3120
gaggcgggtg gtatggagca aggggcccaa gttaacttgt ttattgcagc ttataatggt 3180
tacaaataaa gcaatagcat cacaaatttc acaaataaag catttttttc actgcattct 3240
agttgtggtt tgtccaaact catcaatgta tcttatcatg tctggatccg cttcaggcac 3300
cgggcttgcg ggtcatgcac caggtgcgcg gtccttcggg cacctcgacg tcggcggtga 3360
cggtgaagcc gagccgctcg tagaagggga ggttgcgggg cgcggaggtc tccaggaagg 3420
cgggcacccc ggcgcgctcg gccgcctcca ctccggggag cacgacggcg ctgcccagac 3480
ccttgccctg gtggtcgggc gagacgccga cggtggccag gaaccacgcg ggctccttgg 3540
gccggtgcgg cgccaggagg ccttccatct gttgctgcgc ggccagcctg gaaccgctca 3600
actcggccat gcgcgggccg atctcggcga acaccgcccc cgcttcgacg ctctccggcg 3660
tggtccagac cgccaccgcg gcgccgtcgt ccgcgaccca caccttgccg atgtcgagcc 3720
cgacgcgcgt gaggaagagt tcttgcagct cggtgacccg ctcgatgtgg cggtccgggt 3780
cgacggtgtg gcgcgtggcg gggtagtcgg cgaacgcggc ggcgagggtg cgtacggccc 3840
gggggacgtc gtcgcgggtg gcgaggcgca ccgtgggctt gtactcggtc atggtggcct 3900
gcagagtcgc tctgtgttcg aggccacacg cgtcacctta atatgcgaag tggacctggg 3960
accgcgccgc cccgactgca tctgcgtgtt ttcgccaatg acaagacgct gggcggggtt 4020
tgtgtcatca tagaactaaa gacatgcaaa tatatttctt ccggggacac cgccagcaaa 4080
cgcgagcaac gggccacggg gatgaagcag ctgcgccact ccctgaagat ccatcgtctc 4140
ctaacaagtt acatcactcc tgcccttcct caccctcatc tccatcacct ccttcatctc 4200
cgtcatctcc gtcatcaccc tccgcggcag ccccttccac cataggtgga aaccagggag 4260
gcaaatctac tccatcgtca aagctgcaca cagtcaccct gatattgcag gtaggagcgg 4320
gctttgtcat aacaaggtcc ttaatcgcat ccttcaaaac ctcagcaaat atatgagttt 4380
gtaaaaagac catgaaataa cagacaatgg actcccttag cgggccaggt tgtgggccgg 4440
gtccaggggc cattccaaag gggagacgac tcaatggtgt aagacgacat tgtggaatag 4500
caagggcagt tcctcgcctt aggttgtaaa gggaggtctt actacctcca tatacgaaca 4560
caccggcgac ccaagttcct tcgtcggtag tcctttctac gtgactccta gccaggagag 4620
ctcttaaacc ttctgcaatg ttctcaaatt tcgggttgga acctccttga ccacgatgct 4680
ttccaaacca ccctcctttt ttgcgcctgc ctccatcacc ctgacccccg ctgcgcgggg 4740
gcacgtcagg ctcaccatct gggccgcctt cttggtggta ttcaaaataa tcggcttccc 4800
ctacagggtg gaaaaatggc cttctacctg gagggggcct gcgcggtgga gacccggatg 4860
atgatgactg actactggga ctcctgggcc tcttttctcc acgtccacga cctctccccc 4920
tggctctttc acgacttccc cccctggctc tttcacgtcc tctaccccgg cggcctccac 4980
tacctcctcg accccggcct ccactacctc ctcgaccccg gcctccactg cctcctcgac 5040
cccggcctcc acctcctgct cctgcccctc ccgctcctgc tcctgctcct gttccaccgt 5100
gggtcccttt gcagccaatg caacttggac gtttttgggg tctccggaca ccatctctat 5160
gtcttggccc tgatcctgag ccgcccgggg ctcctggtct tccgcctcct cgtcctcgtc 5220
ctcttccccg tcctcgtcca tgtgccatga tggcggcctg cagctgtgtt cgaggccgcg 5280
cgtgtcacct taatatgcga agtggacctg ggaccgcgcc gccccgactg catctgcgtg 5340
ttcgagttcg ccaatgacaa gacgctgggc ggggagatcc cccttattaa ccctaaacgg 5400
gtagcatatg cttcccgggt agtagtatat actatccaga ctaaccctaa ttcaatagca 5460
tatgttaccc aacgggaagc atatgctatc gaattagggt tagtaaaagg gtcctaagga 5520
acagcgatct ggatagcata tgctatccta atctatatct gggtagcata tgctatccta 5580
atctatatct gggtagcata ggctatccta atctatatct gggtagcata tgctatccta 5640
atctatatct gggtagtata tgctatccta atttatatct gggtagcata ggctatccta 5700
atctatatct gggtagcata tgctatccta atctatatct gggtagtata tgctatccta 5760
atctgtatcc gggtagcata tgctatcctc atgcatatac agtcagcata tgatacccag 5820
tagtagagtg ggagtgctat cctttgcata tgccgccacc tcccaaggag atctgtcgac 5880
atcgatgggc gcgggtgtac actccgccca tcccgcccct aactccgccc agttccgccc 5940
attctccgcc tcatggctga ctaatttttt ttatttatgc agaggccgag gccgcctcgg 6000
cctctgagct attccagaag tagtgaggag gcttttttgg aggcctaggc ttttgcaaaa 6060
agctaattc 6069

Claims (23)

1.一种构建体，其用于表达G蛋白偶联受体蛋白或其亚基，所述构建体在单一载体中从5’侧起依次包含：编码G蛋白α亚基蛋白的核酸、包含IRES序列的核酸、以及编码G蛋白偶联受体蛋白或其亚基的核酸。
2.根据权利要求1所述的构建体，其中，G蛋白偶联受体或其亚基是视紫红质样受体类型或代谢性谷氨酸受体/代谢性信息素受体类型的G蛋白偶联受体。
3.根据权利要求1所述的构建体，其中，G蛋白偶联受体是视紫红质样受体类型的G蛋白偶联受体。
4.根据权利要求1所述的构建体，其中，G蛋白偶联受体为苦味受体。
5.根据权利要求1～4中任一项所述的构建体，其中，载体为质粒载体。
6.根据权利要求1～4中任一项所述的构建体，其中，载体为包含CMV启动子的质粒载体。
7.根据权利要求1～4中任一项所述的构建体，其中，载体为包含CMV启动子及潮霉素抗性基因的质粒载体。
8.根据权利要求1～4中任一项所述的构建体，其中，载体为包含EF1α启动子的质粒载体。
9.根据权利要求1～4中任一项所述的构建体，其中，载体为包含EF1α启动子及嘌呤霉素抗性基因的质粒载体。
10.根据权利要求1～9中任一项所述的构建体，其中，IRES序列为2型的IRES序列。
11.根据权利要求1～10中任一项所述的构建体，其中，IRES序列为来自脑心肌炎病毒的IRES序列。
12.根据权利要求1～7中任一项所述的构建体，其中，在编码G蛋白偶联受体蛋白或其亚基的核酸的5’侧包含编码具有提高G蛋白偶联受体蛋白或其亚基向细胞膜的转移的功能的多肽的核酸。
13.根据权利要求12所述的构建体，其中，提高G蛋白偶联受体蛋白或其亚基向细胞膜的转移的多肽是包含大鼠的生长抑素受体的N末端45个氨基酸的多肽、或包含牛的视紫红质的N末端39个氨基酸的多肽。
14.根据权利要求1～13中任一项所述的构建体，其中，G蛋白α亚基蛋白为Gq家族的G蛋白α亚基蛋白、Gi家族的G蛋白α亚基蛋白、Gs家族的G蛋白α亚基蛋白、或者它们的嵌合蛋白。
15.根据权利要求1～14中任一项所述的构建体，其中，G蛋白α亚基蛋白为Gα16、Gαgust或Gαolf、或者它们的嵌合蛋白。
16.根据权利要求1～15中任一项所述的构建体，其中，G蛋白α亚基蛋白为人Gα16/大鼠Gαgust。
17.根据权利要求16所述的构建体，其中，G蛋白α亚基蛋白为人Gα16/大鼠Gαgust43。
18.根据权利要求1～17中任一项所述的构建体，其中，G蛋白偶联受体蛋白为人的G蛋白偶联受体蛋白。
19.基因导入了权利要求1～18中任一项所述的构建体的转化细胞。
20.物质的生理反应的测定方法，该方法包括：将物质添加于权利要求19所述的转化细胞，对该物质引起的生理反应进行测定。
21.根据权利要求20所述的测定方法，其中，物质为苦味物质、气味物质、鲜味物质或甜味物质、或者对这些物质的调节物质。
22.权利要求19所述的转化细胞在测定物质的生理反应中的用途。
23.一种用于物质的生理反应的测定方法的试剂盒，其包含权利要求19所述的转化细胞，所述测定方法通过将物质添加于该转化细胞、并对该物质引起的生理反应进行测定来进行。
CN201880069162.7A 2017-10-23 2018-10-16 用于表达g蛋白偶联受体或其亚基的构建体及其用途 Pending CN111278981A (zh)

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Cited By (1)

* Cited by examiner, † Cited by third party
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CN108611324A (zh) * 2018-05-07 2018-10-02 云南中烟工业有限责任公司 一种稳定共表达重组人源甜味受体蛋白的真核细胞系及其制备方法

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