CN101353696A

CN101353696A - 包括肝纤维化和/或肝硬化的肝纤维损伤的生物标志及其检测方法

Info

Publication number: CN101353696A
Application number: CNA2007101386023A
Authority: CN
Inventors: 谢惠珠; 曾锱翎; 苏立仁; 黄奇英; 徐士兰
Original assignee: Industrial Technology Research Institute ITRI; National Health Research Institutes
Current assignee: Industrial Technology Research Institute ITRI; National Health Research Institutes
Priority date: 2007-07-24
Filing date: 2007-07-24
Publication date: 2009-01-28

Abstract

本发明提供一种检测肝纤维化损伤的方法，包括肝纤维化和/或肝硬化。其分析生物样本中至少一基因或其人类直向同源的异常表达，且该基因编码一蛋白，其选自序列号：1至63，其中至少一基因的异常表达表示有肝纤维化或肝硬化的发生。本发明还提供试剂盒，包括核酸探针或辨识肝纤维化和/或肝硬化的抗体，以分析编码序列号：1至63基因或其蛋白质及其人类直向同源的异常表达。

Description

包括肝纤维化和/或肝硬化的肝纤维损伤的生物标志及其检测方法

技术领域

本发明涉及关于利用不同基因的异常表达来作为检测肝纤维化和/或肝硬化的方法，以及用来诊断肝纤维化和/或肝硬化的试剂盒。

背景技术

肝纤维化为一种持续性的病症，其特征在于总肝胶原蛋白(total livercollagen)及其它基质蛋白(matrix protein)的增加以至于破坏肝脏的结构及减弱肝脏功能(参考文献1、2)。肝纤维化的发展为对发炎作用的反应，整个的肝纤维化过程属于一种动态发炎及修复的结果，但有机会可被分解而恢复(参考文献3)。纤维化一般认为是肝脏内结痂的形成，若肝长期地受伤及愈合，此情况则称为硬化。

肝纤维化和/或硬化为造成肝细胞癌(hepatocellular carcinoma，HCC)的主要因子。许多的因子，例如，B型肝炎病毒、C型肝炎病毒、肝毒素、代谢失调及酒精中毒皆会产生肝纤维化和/或硬化，且其型态类似(参考文献3-7)，而纤维化的末期即发展成硬化。然而目前对于肝脏损伤及修复的过程中包括何种基因及其表达为何仍不清楚，且上述因子所导致的肝硬化过程通常没有显著的征兆。肝硬化末期的患者若未接受换肝则通常会在1年内死亡，若接受换肝后，有75％的患者可存活5年。

在先前的研究中已揭示39个已知的纤维化或硬化的标志(标记)(参考文献3、8、9)，但其中有些标志须以侵入式采样来获得。

现在在研究其它标志时已经可以利用转录体的生物芯片及蛋白质体的定量分析。生物芯片被广泛地使用于大量基因表达的分析上。通常在以生物芯片分析基因表达时，可同时分析上千种基因的改变以及找出有意义的特征(参考文献10、11)。此外，目前蛋白质体的研究通常是利用二维凝胶电泳法(two-dimensional gel electrophoresis，2DE)及液相层析的同位素亲和标定(ICAT)技术(参考文献12)。近来，对ICAT技术进行改进发展出iTRAQ(isobaric tags for relative and absolute quantitation)技术，ICAT技术及iTRAQ技术皆可在线进行多种标志的鉴定及其蛋白质间的相对量的分析。

发明内容

本发明利用不同的分析方法，例如，生物芯片及蛋白质定量来鉴定出可进行诊断及治疗肝纤维化和/或肝硬化的生物特征。

本发明提供一种检测受试者患肝纤维化和/或肝硬化的方法，包括从患者中获得生物样本，以及分析该样本中至少一基因的异常表达，该基因编码蛋白质，其选自序列号：1至63及其人类直向同源基因(orthologs)，其中该基因的异常表达表示患有肝纤维化和/或肝硬化。本发明还涉及所述至少一基因及其表达的蛋白质在制备检测受试者患肝纤维化和/或肝硬化药物中的用途。

本发明进一步提供一种检测受试者是否患肝纤维化和/或肝硬化的方法，其是由分析生物样本中人类直向同源基因的异常表达来进行的，该基因编码蛋白质，其选自序列号：64至120。本发明还涉及所述基因及其表达的蛋白质在制备检测受试者患肝纤维化和/或肝硬化药物中的用途。

本发明进一步提供一种检测肝纤维化和/或肝硬化的试剂盒，包括一或多种核苷酸探针，其可与至少一基因的核苷酸杂交，该基因编码蛋白质，其选自序列号：1至63及其人类直向同源基因(orthologs)，以及此试剂盒的使用方法。

本发明还提供一种检测肝纤维化和/或肝硬化的试剂盒，包括一或多种核苷酸探针，其可与至少一人类直向同源基因的核苷酸杂交，该基因编码蛋白质，其选自序列号：64至120，以及此试剂盒的使用方法。

本发明另提供一种检测肝纤维化和/或肝硬化的试剂盒，包括一或多种抗体，其可与至少一蛋白质结合，该蛋白质选自序列号：1至63及其人类直向同源(orthologs)，以及此试剂盒的使用方法。

本发明另提供一种检测肝纤维化和/或肝硬化的试剂盒，包括一或多种抗体，其可与至少一人类直向同源基因的蛋白质结合，该蛋白质选自序列号：64至120，以及此试剂盒的使用方法。

本发明另提供一种鉴定化合物的方法，该化合物可降低至少一基因的表达，该基因编码蛋白质，其选自序列号：7至23、42至63及其人类直向同源基因(orthologs)，包括利用细胞，其表达至少一上述基因，使该细胞与试验化合物接触，在该试验化合物的存在下，检测至少一基因的表达的降低，其中该基因表达的降低表示抑制或治疗肝纤维化和/或肝硬化的征状。

本发明另提供一种鉴定化合物的方法，该化合物增加至少一基因的表达，该基因编码蛋白质，其选自序列号：1至6、24至41及其人类直向同源基因，包括利用细胞，其表达至少一上述基因，使该细胞与试验化合物接触，以及在该试验化合物的存在下，检测至少一基因的表达的增加，其中该基因表达的增加表示抑制或治疗肝纤维化和/或肝硬化的征状。本发明还涉及本发明所述物质诸如上面所述化合物在制备抑制或治疗肝纤维化和/或肝硬化的征状的药物中的用途。

附图说明

图1A为以DMN处理以促进大鼠的纤维化的示意图。每周对大鼠注射3次DMN连续3周(以倒三角形表示)，或者是注射生理食盐水作为对照组。每周测量大鼠体重并处死(以三角形表示，由第11天开始，其称为第1周，并持续至第6周)。采集血液样本以进行生化检测(参照图6)，并割除肝脏及测量肝脏重量。接着以甲醛固定肝脏以进行组织病理研究，或分离其中的RNA及蛋白质以进行生物芯片及iTRAQ蛋白质体的分析。

图1B为DMN处理大鼠的转化生长因子-β1(Tgfβ1)的实时PCR(Q-RT-PCR)结果。其显示Tgfβ1的表达较高，而Tgfβ1为强力的纤微化促进因子。

图2A显示DMN处理大鼠的肝组织的组织病理分析。大鼠肝组织可根据组织病理特征分为四种程度的变化：坏死程度由N0至N3(第一列)，发炎程度由I0至I3(第二列)，纤维化的程度由F0至F3(第三列)，以及脂肪变异程度分为表达(+)或不表达(-)于最后一列。

图2B为大鼠模式的组织病理程度。其结果以时间来分类。坏死性发炎指数范围在A0至A6：A0＝无，A(1-3)＝轻微及A(4-6)＝中度坏死性发炎。纤维化可分为2种程度：F(0-1)＝正常的门脉外围纤维化延伸，F(2-3)＝好发型贯穿性肝纤维化且伴随结节的发生。脂肪变异以表达(+)或不表达(-)表示。在每个时间点计数每种组织病理程度的大鼠数目及其所占比例。

图3A显示DMN诱导的大鼠纤维化模式中256种基因的表达树形图。

图3B比较生物芯片与Q-RT-PCR所显示的Timp1表达量，且两者结果一致。在Q-RT-PCR的Timp1分析中，表达量(以矩形表示)为所有基因的表达量的平均值，且以对数表示于右边的纵轴。2种Timp1转录物，rc_AI169327_at及rc_AI169327_g_at(以圆形及三角形表示)相对于所有基因表达平均值的表达量表示于左边纵轴。

图4A显示以iTRAQ蛋白质体分析DMN处理的大鼠及对照组大鼠于第2、4、6周的波形蛋白(vimentin)的表达量。波形蛋白的表达量在DMN处理的大鼠的肝脏中增加2.4-3.4倍。

图4B显示以Western Blotting分析DMN处理的大鼠的波形蛋白(vimentin)的表达量。此结果与iTRAQ蛋白质体分析的结果吻合。

图5显示Western Blotting，以Western Blotting分析正常及B型肝炎的肝硬化病人血清中的碳酸酐酶I的表达。

图6显示对照组及处理组的血清生化检测结果。

图7-1至14显示所选择的63种基因及其人类直向同源基因。

图8A显示以网络分析由生物芯片所鉴定出的基因，标底线者为本发明鉴定得到的基因；标底线的基因中未显示与肝损伤有关的，另以粗体字标示。

图8B显示以网络分析由iTRAQ所鉴定出的基因，标底线者为本发明鉴定得到的基因；标底线的基因中未显示与肝损伤有关者，另以粗体字标示。

为了让本发明的上述和其它目的、特征、和优点能更明显易懂，下文特举较佳实施例，并配合所附图示，进行如下详细说明：

具体实施方式

说明书中所述“生物样本”为任何由一个体的细胞、组织或器官所采集的生物物质。生物样本的来源可为被诊断具特定症状的个体。生物样本可在获得或贮存后进行分析。若需贮存，则样本可贮存于适合的缓冲液，且置于4℃、-20℃、-70℃，或低温液体，例如，液态氮或液态氦。在一实施例中，生物样本可为血液、血清或血浆。在另一实施例中，生物样本可为生物切片或组织样本。在另一实施例中，生物样本可为羊水、乳汁、唾液、脊髓液、淋巴液、汗液、黏膜、滑液、泪液、或其它临床上的样本。

说明书中所述“患者”为哺乳类动物，包括人类、灵长类、家畜及实验动物，但不限于此。

说明书中所述“异常表达”为基因在RNA/mRNA、蛋白质或RNA/mRNA及蛋白质的表达程度上与正常基因的比较，例如，增加或降低基因在RNA/mRNA、蛋白质或RNA/mRNA及蛋白质的表达程度。

说明书所述的“基因”及“基因编码蛋白质”为任何的核苷酸序列或其蛋白质，编码或转录的蛋白质具有一特定功能。基因可包括所有的可编码序列号的功能蛋白的核苷酸，或为与编码及表达序列号蛋白有关的部份核苷酸。核苷酸序列包括正常的序列以及表达序列的外显子、非表达序列的内含子、起始或终止区、启动子序列，其它调控序列或连接区变异的基因序列。

说明书中所述的“人类直向同源”与人类基因有关，其中非人类与人类基因是由一共同祖先的单一基因演化而来，且此人类基因具有相同的功能。

说明书中所述的“探针”为杂交探针，其为寡核苷酸，可利用一基本方法与其互补核苷酸接合。此探针也包含肽核苷酸(Nielsen et al.，1991，(参考文献13))及其它核苷酸类似物及拟核苷酸(nucleic acidmimetics)(U.S.Pat.6156501)。

说明书中所述的“核苷酸”为DNA或RNA/mRNA。例如，组织中的染色体、线粒体、病毒和/或细菌的核苷酸及合成核苷酸。“核苷酸”包括单链或双链核苷酸分子，且还包括一完整核苷酸分子的片断或部分。

说明书中所述的“包装”为一般的包装物质，包括容器外部的标记及内部的物质，更包含使用此试剂盒的操作手册，但不限于此。

说明书中所述的“抗体”为免疫球蛋白或其一部分或其衍生物，且包含任何含有抗原结合部位的多胜肽，可以产生于体外(in vitro)或体内(invivo)。其包括多克隆抗体、单克隆抗体、单特异性(monospecific)抗体、多特异性(polyspecific)抗体、人源化(humanized)抗体、单链抗体、合成抗体、重组抗体、杂交抗体、突变抗体及graft抗体。“抗体”也包含抗体片断，例如，Fab、F(ab’)2、Fv、scFV、Fd及其它抗体片断，其含有抗原结合部位，即具有与特异性抗原结合的能力。一般来说，上述片断包括抗原结合区，例如，抗体分子的一部份，其含有可在抗原与抗体间产生特异性结合的氨基酸。抗原结合区包括抗体轻链可变区(V_L)及抗体重链可变区(V_H)，然而不需两者皆具有。例如，Fd抗体片断仅含有V_H区，但仍具有与完整抗体相同的结合功能。

说明书中所述的“特异性结合”或类似叙述，其意思为二分子形成复合体(complex)，并在生理上维持相对稳定的状态(如稳定的抗原/抗体复合体)。上述叙述也可应用于其它地方，例如，抗原结合结构域(antigen-bindingdomain)为特定的抗原决定位(epitope)，其可在多个分子中发现。因此，只要抗体可与这些蛋白质上所具有的抗原决定位结合，抗体即可特异性的与该蛋白质结合。特异性结合的特征为选择性的反应，通常包括与低至中度反应物量做高亲和性的结合。非特异性结合通常为低选择性的反应，且是与中至高度反应物量做低亲和性的结合。一般来说，当结合至少在低于10⁵M^-1、10⁶M^-1、10⁷M^-1或10⁸M^-1时，为特异性结合。如有需要可改变结合条件来减少非特异性结合，但实质上并不影响特异性结合，此条件为本领域所公知，且可选择熟悉此技术领域者所采用一般技术为适当结合条件。如先前的文献及常用的技术为选择适合的结合条件。上述条件通常为设定抗体浓度、溶液中的离子强度、温度、结合时间、非直接作用的分子(如封阻剂，如血清蛋白、牛奶酪蛋白)的浓度等(Morgan et al.，“The Matrix Effects onKinetic Rate Constants of Antibody-Antigen interactions Reflects SolventViscosity，”J.Immunol.Meth.217：51-60(1998)；及Zhuang et al.，“Measurementof Association Rate Constant of Antibody-Antigen Interaction in Solution Basedon Enzyme-Linked Immunosorbent Assay，“J.Biosci.Bioeng.92(4)：330-336(2001))。

说明书中所述的“蛋白质”为任何长度的氨基酸的聚合体，其可为自然发生或人工合成的氨基酸，编码及非编码氨基酸，肽，depsipeptides，环形、双环形、缩环(depsicyclic)或双缩环(depsibicyclic)的多肽骨架，单链蛋白或完整蛋白质分子的片断或部分。

说明书中所述的“化合物”为物质，其包含一或多个任何比例及任何结构的化学成分，结构可为环状、双环状、支链或直链。化合物可为有机或无机。化合物也可为组合物，包括一或多个化学元素，一或多个草本/植物成份或草本/植物萃取物，或同时具有化学成份及草本/植物成份或萃取物。

具体实施

慢性肝病为亚洲常见及潜在的致命疾病。在肝纤维化的最后时期肝硬化通常会继续发展成肝癌(hepatocellular carcinoma，HCC)。肝纤维化及肝硬化会表达相同的蛋白质，在肝纤维化时，这些蛋白质表达的改变可检测出肝纤维化的识别标志，将有助于肝硬化和/或肝纤维化的诊断。首先，建立肝纤维化的模式。二甲基亚硝胺(dimethylnitrosamine，DMN)，为一种非基因毒素的肝毒素，可促进大鼠的坏死性发炎(necroinflammatory)及肝纤维化(Jezequel A.M.et al.(参考文献14))，为已知用以探讨人类肝病的动物模式。在为期6周的实验中，以组织病理、生物化学及定量RT-PCR确认大鼠模式中肝纤维化的发生。

使用生物芯片及iTRAQ定量蛋白质体技术。iTRAQ技术可同时鉴别多种蛋白质的相对量。应用生命系统公司所开发的iTRAQ试剂，其为具有4种等质量试剂的组合，此4种试剂具胺类特异性，可用以标记肽。此标记肽具有相同的质量也因此在一次MS质谱中是相同的。其在MS/MS质谱分析下产生高强度、不同的、低质量离子特征，可用以同时定量4种不同的样本。例如，分子量114、115、116及117Da的子离子为由4种试剂所裂解出来，利用4种子离子量上的差异即可进行蛋白质定量。因为所有的肽皆被标定，可增加蛋白质的覆盖率且每个蛋白质中分析多个肽可增进准确度(参考文献16)。iTRAQ技术可同时分析多种样品的特性让我们可同时比较不同肝脏状态下的蛋白质表达。

上述大鼠模式与人类肝脏的研究模式相似，因此此研究结果可应用于人类肝脏的临床上。此研究主要利用二甲基亚硝胺(以下简称DMN)来促使肝纤维化，其为一种非基因毒害性肝毒素(参考文献17、18)。如上所述，DMN已被证实可迅速地导致肝脏的损伤且已被证明可用于研究人类纤维化的形成(参考文献14-15、19)，且血清标志(serum marker)的表达可显示大鼠肝纤维模式与对照组的不同，请参照图6，其为人类肝纤维模式的血清标志，例如，血清白蛋白(albumin)、谷氨草乙酸转氨酶(glutamate oxaloacetatetransaminase，GOT)、谷丙转氨酶(Glutamic pyruvic transaminase，GPT)、总胆红素(total bilirubin)、碱性磷酸酶(alkaline phosphatase，AKP)、酸性磷酸酶(acid phosphatase，ACP)、α-胎儿蛋白(α-fetoprotein，AFP)、血清尿素氮(bloodurea nitrogen，BUN)、胆固醇(cholesterol，CHOL)、乳酸脱氢酶(lactatedehydrogenase，LDH)、蛋白素(Golbulin)、凝血酶原时间(Prothrombin time，PT)以及血小板(blood platelets，PLT)。因此由分别利用上述标志可用来诊断人类的肝纤维化和/或肝硬化。

本发明鉴定出可作为肝纤维损伤标志的97种基因。本发明所鉴定出与肝纤维化和/或肝硬化有关的异常表达基因中，有30％已发表于公开的文献(PubMed)中，剩余的70％则完全未发表于任何的文献中。通过生物芯片及蛋白质体定量分析所获得的信息后可挑选出63种基因，此63种基因的表达在DMN处理及无DMN处理中显著的改变，且此结果并无在任何有关肝纤维化或肝硬化的文献中公开(图7)。在DMN处理大鼠中，此63种基因在RNA/mRNA和/或蛋白质程度上与对照组相较下具有异常的表达，且其中有些基因为促进表达(up-regular)有些为抑制表达(down-regular)。此63种基因可通过EnsEMBL及HomologGene数据库转换为人类的直向同源基因(图7：序列号：1至120)。

因此本发明通过研究与肝损害有关的异常表达基因，提供一种用来检测肝纤维化损害的方法。在此检测方法中，编码蛋白质的基因的异常表达包括编码全长蛋白质的全长基因及编码部份蛋白质的部份基因的异常表达。

本发明提供一种检测肝纤维化和/或肝硬化的方法，包括从患者中获得生物样本，分析该样本中至少一基因的异常表达，该基因编码蛋白质，其选自序列号：1至63及其人类直向同源基因(orthologs)，其中该基因的异常表达显示具有肝纤维化和/或肝硬化。在另一实施例中，本发明提供一种检测肝纤维化和/或肝硬化的方法，包括分析至少一种异常表达的基因，该基因为编码蛋白的基因，其选自人类直向同源基因，包括序列号：64至120。

本发明所发现的人类直向同源基因可由Ensembl数据库(http:www.ensemble.org/Rattus_norvegicus/)的gene/protein及HomoloGeneNCBI数据库(http://www.ncbi.nlm.nih.gov/entrez/query.fcgi？db＝homologene)获得。

在本发明中，不同的异常表达基因可利用转录分析或蛋白质体定量分析，如生物芯片、Q-RT-PCR、ICAT及iTRAQ或其它适合的公知技术来进行测定。

在另一实施例中，本发明涉及分析一种或多种促进(up-regulation)或增加表达的基因，该基因编码蛋白质，其选自序列号：7至23及42至63及其人类直向同源基因，其中该基因的增加表达显示肝纤维化和/或肝硬化的存在。在另一实施例中，本发明提供一种检测肝纤维化和/或肝硬化的方法，包括分析至少一种促进表达的基因，该基因编码蛋白质，其选自人类直向同源基因，包括序列号：68至82、100至120。

在另一实施例中，本发明还提供一种分析至少一种或多种抑制(down-regulation)或减少表达的基因，该基因编码蛋白，其选自序列号：1至6、24至41及其人类直向同源基因。在另一实施例中，本发明分析至少一种基因的减少表达，该基因编码蛋白质，其选自人类直向同源基因，包括序列号：64至67及83至99。

本发明还提供一基因丛集(clustering of gene)，因此，本发明提供一种检测肝纤维化和/或肝硬化的方法，包括分析生物样本中至少一基因的异常表达，此基因编码蛋白质，与癌症、细胞周期、细胞形态有关的基因，包括序列号：9、69、12、72、4、65、17、76、7、68、19、78、5、66、20、79、22、81、21及80；与脂质代谢、小分子生化、组织损伤及异常有关的基因，包括序列号：10、70、3、64、14、73、15及74；与血液疾病、内分液系统的发育、功能及神经系统的发育、功能有关的基因，包括序列号：13；与癌症、细胞形态、皮肤疾病及症状有关的基因，包括序列号：8、44、102、45、103、48、106、31、90、35、93、50、108、51、109、40及98；与脂质代谢、小分子生化、分子传输有关的基因，包括序列号：25、84、42、100、27、86、47、105、36、94、16、75、53、111、37、95、38、96及107；与癌症、细胞移动、细胞生长及分化有关的基因，包括序列号：59、117、46、104、30、89、52、110、58、116、55、113、39、97、56、114、57及115。

诊断试剂盒

本发明还提供一种利用上述基因和/或蛋白质所完成的诊断试剂盒。在一实施例中，提供一种可用来诊断肝纤维化和/或肝硬化的试剂盒，其包括一或多种核苷酸探针，此探针可与至少一种基因的核苷酸分子杂交，此基因编码蛋白质标记，其序列号选自序列号：1至63及其人类直向同源基因，以及包括显示用以检测肝纤维化的组合。此试剂盒可检测上述基因的异常表达，例如，促进表达(up-regulation)或抑制表达(down-regulation)，此异常表达可表示肝纤维化和/或肝硬化。在另一实施例中，本发明还提供一种用来诊断肝纤维化和/或肝硬化的试剂盒，包括核苷酸探针，其可与至少一种基因的核苷酸分子杂交，此基因编码蛋白质标记，序列号选自序列号：1至63及其人类直向同源基因。这些基因的异常表达可显示纤维化和/或硬化。在另一实施例中，此诊断试剂盒包括一或多种核苷酸探针，其可与至少一种人类直向同源基因的核苷酸分子杂交，包括序列号：64至120，以用来诊断肝纤维化和/或肝硬化。

此试剂盒的制备可以为任何的公知技术完成。例如，标定此探针，以公知的标定技术来检测，包括放射线同位素或荧光标定等，但不限于此。此探针可与核苷酸分子杂交，其可为单链和/或双链的核苷酸分子，且包括任何完整核苷酸分子的片断或一部分。

核苷酸杂交会受到盐类浓度、温度或有机溶剂影响，甚至是碱基组合物、互补链的长度、配对错误的核苷酸碱基数等，其已充分地公开于公知技术中。杂交条件的严格条件(stringency condition)与核苷酸的长度及碱基组成有关，其也充份地揭露于公知技术中。一般来说，严格条件可利用杂交及清洗步骤中的操作温度、盐类浓度来改变或控制。例如，高温及低盐可增加严格度。上述条件皆为公知技术，其可参考Strauss，W.M.“Hybridizationwith Radioactive Probes”in Current Protocols in Molecular Biology 6.3.1-6.3.6.(John Wiley)，液态及非液态条件皆详述于先前文献中。

在一严格度的杂交条件中，可在0.1×SSC(15mM氯化钠/1.5mM柠檬酸钠)在50℃或更高的温度下进行。在另一高严格度的杂交条件中，可于42℃，50％二甲基甲酰胺(formamide)，1×SSC(150mM氯化钠/15mM柠檬酸钠)，50mM磷酸钠(pH 7.6)，5×丹哈德溶液(Denhardt’s solution)，10％(w/v)葡聚糖硫酸盐(dextran sulfate)及20μg/ml变性鲑鱼精子DNA(salmon spermDNA)的条件下反应一夜，接着在65℃以0.1×SSC清洗。在更高严格度的杂交条件中，可为液态杂交(如无二甲基甲酰胺)，以6×SSC(20×SSC中含有3.0M氯化钠及0.3 M柠檬酸钠)、1％(w/v)十二烷基硫酸钠(Sodium DodecylSulfate，SDS)于65℃杂交约8小时(或更久)，接着以65℃的0.2×SSC，0.1％SDS溶液清洗一至二次。

中度严格度的杂交条件可使一核苷酸与其互补核苷酸至少有60％，或至少有75％，或至少有85％，或大于95％的同一性的核苷酸结合。杂交的严格条件通常可通过个别或同时降低杂交及清洗温度、增加杂交溶液中的二甲基甲酰胺，和/或增加清洗缓冲液的盐浓度来降低。中严格度的杂交条件可包括，例如，溶液杂交(如无二甲基甲酰胺)，以6×SSC，1％(w/v)SDS于65℃进行约8小时(或更久)，接着以室温的2×SSC，0.1％SDS溶液清洗一至二次。在另一中严格度的杂交条件中，包括，以6×SSC、5×丹哈德溶液(Denhardt’s solution)、0.5％(w/v)SDS及100μg/ml超声波震荡的鲱鱼鲑或鱼精子DNA(salmon sperm DNA)，于42℃下进行杂交，接着以65℃的2×SSC及0.1％(w/v)SDS清洗。此外，由熟悉此技艺人士可由已公开的文献了解其它的置换或可能的安排皆属于本发明的范围内。

在另一实施例中，本发明提供一种用于诊断肝纤维化和/或肝硬化的试剂盒，包括一或多种抗体，其可特异性地与至少一蛋白质结合，此蛋白质序列号选自序列号：1至63及其人类直向同源基因，且还包括用来检测肝纤维化和/或肝硬化的使用手册。在另一实施例中，此试剂盒包括一或多种抗体，其可特异性地与至少一人类直向同源蛋白质结合，此蛋白质序列号选自序列号：64至120，且还包括用来检测肝纤维化和/或肝硬化的使用手册。上述基因的异常表达显示了肝纤维化和/或肝硬化的存在。

特异性的抗体可由一般公知的单克隆抗体或多克隆抗体技术完成。此抗体可标记放射性同位素，例如，³⁵S、¹⁴C、¹²⁵I、³H、¹³¹I，请参考CurrentProtocols in Immunology(参考文献20)。此放射线可以闪烁计数(scintillationcounting)的方式测量。此抗体也可为标志荧光，例如，稀土螯合物(rare earthchelates)、Texas Red、rhodamine、荧光、丹磺酰(dansyl)、玫瑰红(Lissamine)、伞型酮(umbelliferone)、phycocrytherin、藻蓝素(phycocyanin)，或其它商品化的荧光，例如，SPECTRUM ORANGE及SPECTRUM GREEN和/或其衍生物等。上述荧光标志可与抗体结合，相关结合方法可参照Current Protocolsin Immunology，supra等。荧光可用荧光仪测定。

蛋白质的异常表达可利用抗体再配合其它公知技术来测定，例如，Western Blotting或酶联免疫吸附法。Western Blotting首先为一电泳步骤，其利用十二烷基磺酸钠-聚丙烯酰胺凝胶电泳(SDS-PAGE)，依蛋白质的大小及带电荷，将欲研究的蛋白质分离出来，相关技术可参考SAMBROOK ETAL.，3 MOLECULAR CLONING：A LABORATORY MANUALA8.40-A8.45(2001)(其中描述有关以SDS-PAGE分离蛋白质的各种试剂及方法)，将凝胶中的蛋白质转渍到硝化纤维(nitrocellulose)、尼龙(nylon)、氟化氟亚乙烯(PVDF)，或适用于一般固定及Western Blotting的其它膜或滤纸，上述固定及Western Blotting的标准技术与公知技术相同。上述转渍方法可为湿式(immersion)或半干式(semi-dry)的转渍法，也可为其它公知技术。接着将蛋白质固定于膜或滤纸上，以避免在后续Western Blotting的多次的杂交、清洗、及染色步骤中流失目标蛋白。固定的方法可由，热、紫外线交联反应(cross-linking with ultraviolet light)或其它公知方法达成(参照Sambrook et al.，3 Molecular cloning：A laboratory manual A8.52-A8.55(其中描述有关免疫印迹及检测抗原/抗体复合体的方法))

并以缓冲溶液(如磷酸缓冲液(phosphate-buffer saline，PBS)等其它类似溶液)来封阻经固定的膜或滤纸上的非特异性抗体结合位置，上述缓冲溶液中含有封阻剂，如0.5％(w/v)的低脂奶粉或5％(w/v)的牛血清白蛋白(BSA)等。封阻后，加入一次抗体与膜或滤纸反应，在与一次抗体反应完成后，清洗上述膜或滤纸，并以二次抗体辨识自体抗体/自体抗原复合体，上述二次抗体上标记有可发光的(chromogenic)、荧光的(fluorogenic)或化学发光的物质(chemiluminescent means)。上述的自体抗体/自体抗原复合体可以比色法(如辣根过氧化酶(horseradish peroxidase)and TMB)或自动放射显影法(如碱性磷酸酶)检测。若利用比色法或化学发光法，则此颜色或荧光的量可以发光检测仪(luminometer)、分光光度计(spectrophotometer)或其它类似仪器来测量。若为自动放射显影法，则抗体结合的量可以光密度或其它类似仪器测量曝光的x光片得知(参照Sambrook et al.，3Molecular Cloning：A laboratorymanual A8.52-A8.55(其中描述有关免疫印迹及检测抗原/抗体复合体的方法))。

Western Blotting所用的二次抗体不管为单克隆或多克隆抗体，可在二次抗体上以公知的技术标记上一配位体(如生物素)或可检测的标志(如荧光或酶)。较适合的标记包括荧光团(fluorophores)、发色团(chromophores)、电密度试剂(electron-dense reagents)(如金或银)、酶及可特异性与他物质结合的配位体。酶如辣根过氧化酶或碱性磷酸酶通常是检测其活性。例如，辣根过氧化酶可使四甲基联苯胺(TMB)转变成蓝色并以分光光度计定量。其它较适合的配位体和/或可检测的标志包括生物素、抗生物素蛋白(avidin)、或链霉抗生物素(streptavidin)、IgG、蛋白质A(protein A)及众多已知的附加受体-配位体组合。对于公知此技术的人所进行的显而易见的其它替换及可能的安排皆属于本发明的范围内。

酶联结合免疫吸附法(ELISA)开始为抗原吸附步骤，一种或多种目标抗原吸附于微量滴定盘(microtiter plate)的反应槽中(参照Kirkegaard & Perrylaboratories，Inc.，Technical Guide for ELISA 9-13(2003)，available athttp://www.kpl.com/home.cfm#(last accessed November 3，2005)(介绍ELISA的各种微量滴定盘和多种将蛋白质包覆于反应槽的方法及试剂)。一般抗原常用的吸附缓冲液包括50mM碳酸盐，pH＝9.6；10mM Tris-HCl，pH＝9.6；10mM PBS，pH＝7.2。上述缓冲液适合用于许多蛋白质。若上述一种或多种抗原无法被吸附于微量滴定盘的反应槽表面，也可使用一般商品化的微量滴定盘，其表面经过修饰，可利用各种化学方法使蛋白质以共价键方式结合于表面上。在蛋白质的吸附过程中，时间及温度皆为重要的影响因子。

将目标抗原涂覆于微量滴定盘上后，以封阻缓冲液清洗微量滴定盘来去除非特异性的结合及降低假阳性的发生(id at 13-14)(介绍封阻的方法及试剂)。一般常用的封阻试剂为蛋白质溶液，如BSA(于PBS浓度介于约1％至5％(w/v)之间，pH＝7.0)、脱脂奶粉、酪蛋白(脱脂奶粉的主要蛋白质)、或酪蛋白酸(caseinate)(溶解性较酪蛋白高，以氢氧化钠做部份切割)、一般的血清(浓度介于约1％至5％(v/v)之间)及明胶(浓度约介于1％至5％(w/v)之间)或非离子性的清洁剂如Tween-20^TM及Triton X-100^TM。

一般会选择可破坏各反应成分间低亲和性交互作用的缓冲液做为清洗缓冲液(wash buffer)，因其会影响检测特异性抗原-抗体作用的能力(id.at14-15(介绍清洗微量滴定盘的各种方法及试剂))。清洗溶液通常具有生理缓冲液(physiological buffer)以避免抗原及结合抗体变性，且可维持酶的活性。在中性酸碱度下的缓冲液，如PBS、Tris-saline、十一烷基咪唑盐(imidazole-buffered saline)等常被广泛地使用。在特定的分析实验中，应依特定的检测试验所采用方法而选择特定的缓冲液。同时，清洗缓冲液也应含有非离子的清洁剂如Tween-20^TM及Triton X-100^TM等，浓度在0.01％至0.05％(v/v)之间，以避免反应成分间低亲和性及非特异性的结合。

封阻程序后，清洗微量滴定盘的反应槽，加入一次抗体以与吸附于的抗原反应，在一次抗体作用完成后，清洗反应槽并加入已标记可发光(如辣根过氧化酶及TMB)、可发荧光或化学发光物质(如碱性磷酸酶)的二次抗体来检测自体抗原-自体抗体复合体(id at 15-21(介绍抗体的制备及使用，与一般常用的于检测物质))。可利用发光检测仪(luminometer)、分光光度计(spectrophotometer)等其它类似仪器来计数光度或荧光强度。标准酶免疫分析方法有多种常见的变化形式，如竞争型ELISA、三明治ELISA等。熟悉此技艺人士可依想检测的抗体、所使用的抗原、抗原和/或一次抗体的来源、及实验上相关的参数而选用适合的方法。对于公知此技术的人所进行的显而易见的其它置换及可能的安排皆属于本发明的范围内。

筛选方法

本发明另提供一种鉴定化合物的方法，此化合物可降低至少一基因的表达，此基因编码蛋白质，其序列号选自序列号：7至23及42至63及其人类直向同源基因。此方法提供至少表达一上述基因的细胞，将此细胞与一试验化合物接触以测定此试验化合物是否可降低上述的异常表达，其中的基因表达的降低表示肝纤维化和/或肝硬化的停止或复原的征兆。此方法也可鉴定化合物，此化合物可增加至少一基因的表达，此基因编码蛋白质，其序列号选自序列号：1至6及24至41及其人类直向同源基因。

【实施例】

1.大鼠肝纤维化模式的建立

本发明利用DMN来产生一大鼠的肝纤维化模式。DMN为一强大的肝毒素，其可攻击肝脏并导致肝纤维化。在以DMN处理后，组织病理的改变包括胶原蛋白的快速沉淀、纤维化的主要蛋白质及造成纤维化的重要程序。在大鼠受DMN所诱导的肝损伤中包括许多特征，例如，门静脉高压腹水(portal hypertension ascites)及其它组织病理与生化的异常表达。由前面的研究可知，由DMN所诱导的大鼠肝损伤可反应出人类肝纤维化和/或肝硬化，且其可作为人类肝纤维化和/或肝硬化的动物模式(参考文献15)。此受DMN诱导的肝纤维化模式可参考Jezequel A.M.et al.(参考文献14)。在本实施例中，使用雄性Sprague-Dawley(Slc：SD；Japan SLC，Shizuoka，Japan)大鼠，重约300至350g。在实验开始后6周，将DMN(Sigma，Saint Louis，MO)腹腔注射至大鼠体内。DMN溶于一般的生理食盐水(Normal Saline)中，于前三周连续投与三天，投与量为6.7mg/kg。注射的时间点如图1A的倒三角形所示。本实施例使用比其它实验较低的注射量，在其它实验中可能使用100mg/kg/day的注射量，此注射量会对大鼠的肝脏产生毒性(参考文献21、22)。

二至七只大鼠在每个时间点投与DMN或以相同体积的不含DMN的生理食盐水作为对照组(包括26只DMN实验组及24只对照组)。分别在第11、18、25、32、39及46天时分别测量大鼠体重并处死。图1A中所示的三角形分别表示第1至6周。

为证明大鼠肝纤维化模式的建立，将会进行Q-RT-PCR分析、血清分析及组织病理分析。

DMN诱导肝损害的组织病理实验

在大鼠处死后，将其肝组织移除以进行组织病理实验。将固定的肝组织进行石蜡包埋，制备成5μm的切片以进行苏木精(hematoxylin)、伊红(eosin)染色(用以观察坏死发炎及脂肪的变异)以及Sirius red/fast green胶原蛋白染色(用以观察纤维化)(参考文献23)。脂肪变异可分为表达(+)或不表达(-)。

图2A显示因DMN诱导肝损害所产生的外表形态改变。参照第2A图，此DMN诱导肝纤维化的代表形态可以四种组织的病理特征(坏死(necrosis)、发炎、纤维化及脂肪变异)量化来表示，坏死指数为N0至N3，发炎指数为I0至I3。肝纤维的量化分析系统为Hepatitis Activity Index(HAI)量化系统的改良(参考文献29、30)。纤维化可分为4种分数：正常(F0)、门脉外围的纤维化延伸(F1)、贯穿性肝纤维化(F2)及好发型贯穿性肝纤维化且伴随结节(focal nodule)的发生(F3)。脂肪变异分为表达(+)或不表达(-)。脂肪变异的照片倍率为200X，其余的为100X。

图2B显示大鼠模式的组织病变量化数值。数值结果以时间排列。坏死性发炎指数为坏死指数及发炎指数的总和，其范围在A0至A6。坏死性发炎可分为3种等级：A0＝无，A(1-3)＝轻微及A(4-6)＝中度坏死性发炎。纤维化可分为2种等级，F(0-1)＝正常的门脉外围纤维化延伸，F(2-3)＝好发型贯穿性肝纤维化且伴随结节的发生。脂肪变异以表达(+)或不表达(-)表示。在每个时间点计数每种组织病理程度的大鼠数目及其所占比例。

参照图2B，在前两周，有75％的DMN处理大鼠具无(F0)或低程度的纤维化(F1)。在第三至第四周，有90％的DMN处理大鼠具高度纤维化，具贯穿性肝纤维化(F2)或好发型贯穿性肝纤维化且伴随结节的发生(F3)。在最后二周，仍有78％的DMN处理大鼠为F2及F3。而脂肪变异仅发生于少部份DMN处理的大鼠(3.7％)。相比较，对照组并没有不正常的病理形态。此外，对照组及DMN处理大鼠的肾脏及脾脏皆没有显著的不正常(未图示)。经由DMN处理的肝损害的坏死性发炎及纤维化指数系统可显示显著的坏死及发炎发生于损害的前期(第1-4周)，接着于第3-6周形成纤维化。在DMN处理后3周，可发现胶原蛋白纤维沉淀，并伴随胆管增生、肝小叶中心坏死(centrilobular necrosis)、贯穿性肝纤维化以及静脉外围纤维化。

定量RT-PCR(Q-RT-PCR)

为进一步对所建立的动物模式进行研究，以Q-RT-PCR测定转化生长因子-β1(transforming growth factor，Tgfβ1)基因的表达，其为已知在肝纤维化的细胞中最强的纤维化促进者，其可促进脂肪细胞的转化(adipocytetransformation)(参考文献24-27)。将相同的总RNA样本以生物芯片及Q-RT-PCR进行分析。RNA的沉淀及分析可参考Affymetrix’s(Santa Clara，CA，U.S.A.)指南。对每一样本进行三次的TaqMan

分析，并取其平均值。为了校准测定基因的量化，需定量同一测定盘中的每一样本的18S核醣体RNA(18S rRNA)。Q-RT-PCR的结果显示DMN处理大鼠的Tgfβ1mRNA的表达量大于对照组(第1B图)。此改变可参照Jezequel A.M.et al.(参考文献14)的内容，因此，上述试验结果可支持DMN诱导的大鼠肝纤维化模式。

分析DMN诱导的大鼠肝纤维化模式中的血清生化数值

将所有50只的大鼠血清进行各项与肝损害相关的生物测试。由大鼠尸体中采集血液样本，并利用Hitachi 747及ACL 3000临床化学分析系统(MYCO，Renton，Washington)测定血清白蛋白(albumin)、谷氨草乙酸转氨酶(glutamate oxaloacetate transaminase，GOT)、谷丙转氨酶(Glutamic pyruvictransaminase，GPT)、总胆红素(total bilirubin)、碱性磷酸酶(alkalinephosphatase，AKP)、酸性磷酸酶(acid phosphatase，ACP)、α-胎儿蛋白(α-fetoprotein，AFP)、血清尿素氮(blood urea nitrogen，BUN)、胆固醇(cholesterol，CHOL)、乳酸脱氢酶(lactate dehydrogenase，LDH)、蛋白素(Golbulin)、前凝血素时间(Prothrombin time，PT)以及血小板(bloodplatelets，PLT)的浓度及活性。在比较经DMN诱导的样本与对照组后，有13种血清标志的表达异常，且证实DMN处理组具有肝脏的损害。DMN处理组的生化数据显示有许多的血清标志改变，且蛋白质的表达量及物理反应皆类似于人类肝脏损害的表现形态(参考文献1、2)。此外，本试验所分析的13种血清标志与测量人类肝脏损害的血清标志相同。

2.DMN诱导肝纤维化时的基因表达情况的建立

生物芯片的分析

用于生物芯片分析的总RNA以Spectra Max Plus(Molecular Devices，Sunnyvale，CA，U.S.A.)测定，且其A260/A280为1.9至2.1之间。杂交、清洗及染色的程序及试剂可参考Affymetrix’s指南(http://www.affymetrix.com/support/technical/manuals.affx)被标定的cRNA可杂交至Affymetrix GeneChip Test 3芯片上以分析先前杂交至AffymetrixGeneChip Test 3芯片上的RNA的性质。

数据的分析及群聚演算(clustering algorithm)

将生物芯片的影像以GnenChipOperating Software(SCOS)(Affymetrix)转换成文字文件，其中含有强度信息，接着将此生物芯片数据以GnenSpring

7.2 Software(Silicon Genetics，Redwood City，CA，U.S.A.)分析。

基因表达特征(gene expression profiling)

在实验开始后6周，取12只对照组大鼠及12只DMN处理组(每个时间点各2只)的肝组织进行生物芯片分析实验。将任何统计分析应用于生物芯片数值之前，已先分析其再现性。将所有生物芯片经过完全配对(perfectmatch(PM))/错误配对(mismatch(MM))的演算后，可筛选出各基因。分析8799种探针，在芯片上可发现2385种转录物(trancripts)(P＜0.05)。为了证明对照组及DMN处理组彼此间的内部样本没有模糊差异，及为判断倍数的改变可视为有显著差异，比较了24组数据的表现情形。比较生物芯片上2385种转录物表达量的散布图，以线性回归分析各芯片的关系。结果显示其并无统计上的差异，仅3.2％的转录物差异在2倍以上。为研究各时间(time course)的差异，分析对照组在第1周及第6周的2385探针，结果同样为无统计上的差异，仅4.6％的转录物差异在2倍以上。相较之下，在对照组及DMN处理组间可发现显著差异，有28.7％的转录物差异在2倍以上。

首先，为了将假阳性的程度降至最低，将筛选所有的转录物，其方法为将生物芯片的数值分为二个独立的群集，且鉴定其是否显著差异。进一步分析比较对照组及DMN处理组发现，在第一群集的2385转录物中有268个表达异常的转录物，其为高于或低于1.5倍以上。第二个方法为利用“detection flag”筛选，其显示在DMN处理组中有23个转录物为“表达”，但对照组则无，且在所有的DMN处理组中，只有1个转录物显示“不表达”，在但对照组中显示“表达”。

总而言之，在比较对照组及DMN处理组后发现，有292个转录物所代表的256个基因具有异常表达，其中有137个为促进表达(up-regulation)而119个为抑制表达(down-regulation)。参照第3图，以阶层式分群法(hierarchical clustering)画出24个样本中与292个转录物相关的基因表达树形图。其中各行(row)表示单独的转录物，各列(column)表示各时间的样本。各细胞的颜色代表各对应组织的表达量，可作为其表达量。以0.25至4的荧光强度来表示每一样本的表达程度。

定量实时反转录聚合酶连锁反应(Q-RT-PCR)

为了进一步确认生物芯片所得到的结果，对金属蛋白酶组织抑制物1基因(Timp1)、金属蛋白酶组织抑制物1基因(Timp2)、基质金属蛋白酶3基因(Mmp3)、谷丙酸转氨(Ggtp)以Q-RT-PCR进行分析。上述基因在本生物芯片(GeneChip)及先前研究中皆可被观察到，可用来证明生物芯片的数值。

由Q-RT-PCR分析结果可知，Timp1(第3B图)、Timp2、Mmp3、Ggtp(未图示)及Tgfβ1(第1B图)在DMN处理组中有显著的提升。上述5种基因的Q-RT-PCR分析结果与先前的文献一致(8、9)。

此外，由生物芯片与Q-RT-PCR的结果可发现彼此有良好的一致性。参照第3B图，在DMN处理组中，由生物芯片与Q-RT-PCR的分析可发现Timp1的表达量提升20倍。对每一样本进行三次的TaqMan

分析，并取其平均值(以矩形表示)。为了校准Timp1转录物的量，须定量同一测定盘中的每一样本的18S核醣体RNA，其以对数表示于右边纵轴。2种Timp1转录物，rc_AI169327_at及rc_AI169327_g_at(以圆形及三角形表示)，将所有基因表达量的平均值以相对应的数值表示于左边纵轴。生物芯片与Q-RT-PCR所显示的Timp1表达量具有高度的一致性(Pearson相关系数分别为0.79及0.92)(第3B图)，表示本实验所测得的基因表达量非常可靠，可用来做进一步研究。

纤维化候选基因(fibrosis candidate genes)

在大鼠模式中已发现坏死性发炎及纤维化在肝纤维化中扮演很重要的角色(参考文献8、23、24、29、30)。为了清楚了解组织病理形态上的因子，将所有大鼠样本以组织病理估算(Histopathological evaluation)分成坏死性发炎(A0-A6)及纤维化(F0-F3)，如第2B图所示。独立t检定(Student-t Test)可以2个次组(F(0-1))及(F(2-3))纤维化指数差异为基础来分析与纤维化相关的基因。若P-值(P-value)小于0.05则代表具有统计上的差异。

以独立t检定(Student-t Test)分析256种基因在DMN处理组的表达是否高于或低于对照组1.5倍以上。在以2个变异组(F(0-1))及(F(2-3))及5％的可信度下，可鉴定出62个异常表达的基因(32个为促进表达(up-regulated)及30个为抑制表达(down-regulated)。此结果与先前的研究符合，Timp1、D63及annexin A1(Anxal)在肝纤维化中具有类似的基因表达形态(参考文献31-34)。

Timp1为一已知的纤维化标志，其可在肝纤维化时间扮演一重要的角色。在肝损害的后期，肝星状细胞(Hepatic stellate cell，HSC)表达一基质金属蛋白酶群组，其会分解正常的肝脏基质，而抑制肝纤维中胶原蛋白纤维(fibrillar collagens)的分解。Timp1的表达量增加会抑制全面性肝纤维胶原蛋白被胶原酶(interstitial collagenases)分解(MMP-1/MMP-13)。参照第3B图，在DMN处理组中，Timp1的表达量可增加20倍以上。

CD63为一种穿膜蛋白(transmembrane protein)，为纤维基因标志，且在DMN处理后表达量会增加。肝星状细胞(HSCs)可活化或分化类肌成纤维细胞(myofibroblast-Iike cell)具收缩、前发炎及促纤维化性。活化的肝星状细胞(HSCs)在纤维化的过程中，会迁移及累积于组织恢复的部位并分泌大量的细胞外基质蛋白(extracellular matrix protein)。活化的肝星状细胞已被视为一种主要的胶原蛋白产生细胞(胶原蛋白为一种细胞外基质)，且为在损伤时的一种肝纤维化起始者。因此证明CD63的抑制可作为肝损伤的新的诊断标志

在酒精性肝病(ALD)的研究中，发现在肝损伤后，膜联蛋白A1(AnnexinA1)(Anxal)会大量的表达。在酒精所引发的肝脏损伤是透过发炎反应。酒精性肝病包括持续性的肝损伤、纤维化及减弱肝脏的再生。因此表示Anxal在纤维化的过程中扮演重要的角色。

由上述可知，此三种基因在上述试验中与先前的研究结果符合，表示在肝脏损害及修复过程中，但却无病征时，生物芯片在监视分子上为一种有力的方法，且在上述试验中鉴定出来的识别基因可成功地辨别低组织病理组(low-score histopathology group)及高组织病理组(high-scorehistopathology group)。此外，上述基因与纤维化有关，且可作为检测纤维化的标志。

3.在DMN诱导肝纤维化过程中，蛋白质的表达情形

在此实施例中，利用iTRAQ标定来鉴定肝脏中异常表达的蛋白质。

同位素标定法：样本的制备及试剂的标定

以6个对照组及6个DMN处理组大鼠的肝组织进行两次重复的iTRAQ标定实验。将肝组织以液态氮冻结后，利用预先以液态氮降温的研磨棒研磨成粉末。接着移除液态氮以及将粉末状的组织分装至试管并储存于-80℃。将20％(w/v)的分解缓冲液(lysis buffer)(包含2％(w/w)SDS溶于pH7.6的磷酸缓冲液)加至粉末状的组织中并置于室温1小时，将样本以12000rpm离心10分钟，取出上层液并加入6倍体积的丙酮，将试管置于-20℃直到沉淀产生。接着小心地倒出丙酮，以0.1％SDS及6M尿素的溶解缓冲液(dissolutionbuffer)使沉淀物再回溶(参考iTRAQ试剂盒，Applied Biosystems，Foster City，CA，U.S.A.)。

利用考马斯蛋白质分析试剂(Coomassie Plus Protein Assay，PIERCE，Rockford，IL，U.S.A.)分析蛋白质的含量。取200μg的蛋白质与以相同体积的溶解缓冲液(含0.1％(w/v))稀释。将蛋白质分解及进行半胱氨酸封阻(blocked)，上述步骤请参考iTRAQ说明书(iTRAQ protocol，AppliedBiosystems，Foster City，CA，U.S.A.)。加入4倍体积的溶解缓冲液至每一个试管中，且以20μg的胰蛋白酶(trypsin)于37℃中处理16小时。从对照组及DMN处理组的肝组织中分离胰蛋白酶水解后的肽，并在每个时间点中分别标定iTRAQ 114及115试剂。

肽的分离及分析

将不同同位素标定的肽混合并以10mM的磷酸(于25％(v/v)乙腈及75％H₂O)酸化，使总体积为4.0ml，并用于强效阳离子交换层析分析(Strongcation exchange(SCX)chromatography)。将处理完成的样本注入液相层析仪(Ettan，GE Healthcare Bio-Science，Umea，Sweden)，以2.1mm×200mm且含有5μm颗粒、300

孔径的Polysulfoethyl A管柱于0.08ml/min的流速中进行分析。相同样本的保护管(Guard Column)衔接于分析管柱的前方。层析液包括A缓冲液，其为10mM KH₂PO₄、pH3.0，25％(v/v)乙腈，以及B缓冲液，其为10mM KH₂PO₄、1M KCl、pH3.0，25％(v/v)乙腈。洗提梯度以层析16ml的缓冲液所需时间内由0％线性增加为40％的B缓冲液然后在4ml缓冲液所需层析时间内直线增加为100％的B缓冲液。分为30个分管收集并利用快速真空离心来干燥。所有的分离液以PepClean^TM C-18spin管柱(PIERCE，Rockford，IL，U.S.A.)去除盐分，将去除盐分的肽利用快速真空离心干燥，并以搭配nanoLC的液相层析质谱仪进行分析。此nanoLC系统由LC组装(Amsterdam，The Netherlands)而成，其连结至一API QSTAR PulsarHybrid QqTOF质谱仪(Applied Biosystems/MDS Sciex，Foster City，CA，U.S.A.)。利用逆相C18管柱(75μm直径x15cm长度，3μm的颗粒)来分离肽，其以两段冲提梯度分别为45分钟由5％变换至50％的B缓冲液及10分钟由50％变换至95％的B缓冲液，流速为0.2μl/min(A缓冲液：2％(v/v)乙腈、0.1％(w/v)甲酸；B缓冲液：80％(v/v)乙腈、0.1％(w/v)甲酸)。MS及串联的MS(MS/MS)的m/z分析范围分别为400-1200Da及75-1500Da。MS/MS质谱分析用内径10μm的硅制tip以连续冲提模式分析。MS/MS质谱仪分析则以ProQUANT 2.0(Applied Biosystems/MDS Sciex，Foster City，CA，U.S.A.)来比对NCBI的rat.fasta数据库。其正确性分别为MS为0.5Da，而MS/MS为0.5Da，图谱比对的筛选条件为可信度须大于95且分数须大于20。经过MS/MS分析后，计算波峰下面积的比例，可得知肽的量。蛋白质的相对含量为所测得肽的平均值。

为了确认由iTRAQ所获得的数值，将比较在iTRAQ试验中以质谱仪分析所得的波形蛋白(vimentin)以及利用Western Blotting以抗波形蛋白抗体所获得的结果。蛋白质以pH值7.6，含2％(w/v)SDS的磷酸缓冲液萃取自对照组及DMN处理组的大鼠肝脏。在经过12％的SDS-PAGE后，将蛋白质转渍至氟化氟亚乙烯膜(PVDF)上，并以小鼠抗波形蛋白抗体单株抗体(Chemicon，Temecula，CA，U.S.A.)进行免疫染色1小时，接着以辣根过氧化酶标定的山羊抗大鼠IgG抗体进行免疫染色1小时。利用增强式化学发光系统(ECL，Perkin-Elmer Life Sciences，Wellesley，MA.U.S.A.)检测上述免疫反应的条纹。参照第4图，Western Blotting与质谱仪的定量结果相符合。

结果

若将可信度设为95％时，所鉴定到的肽的数目的最少为624，最多为1591。多数肽被鉴定一次以上。其中超过351个独特的蛋白质被鉴定出来，相较于对照组，有39个蛋白质在DMN处理组的F2及F3纤维化程度的肝组织中表达异常(差异1.5倍以上)。在此39个蛋白中，有些已知与纤维化的形成有关，例如，纤维蛋白原(fibrinogen)及纤连蛋白(fibronectin)。

在先前研究中已发现，在DMN处理的大鼠中会增加纤维蛋白原的表达。此结果与以氯仿诱导大鼠肝损害模式(model CCl4-induced rat liverdamage)的纤维蛋白原基因表达相同。此氯仿诱导大鼠肝损害也显示在短期的肝脏损害及肝纤维化中，增加纤维蛋白原的mRNA表达，且纤维蛋白原/纤维蛋白(fibrinogen/fibrin)沉淀。纤维蛋白原包括一个肽链，其可使胶原蛋白、纤维蛋白及肝磷脂附着于细胞上，其被包含在血栓中，且在伤口复原时，可促进组织附着于细胞上。在氯仿诱导大鼠肝损害模式中，纤维链蛋白与第I及第III型胶原蛋白已知可作为肝硬化的特征。

此外，甘胺酸-N-甲基转移酶(glycine N-methyltransferase，Gnmt)、醛缩酶(aldolase A，Aldoa)、肌球蛋白轻多肽(Myosin light polypeptide 6，My16)及细胞质内γ肌动蛋白(cytoplasmicγactin，Actrγ)在RAN表达芯片及蛋白质体的研究上皆具有异常的表达。

4.网络分析

为了更进一步分析纤维化肝中异常表达的基因，利用Ingenuity PathwayAnalysis(IPA)(Ingenuity Systems，Mountain View，CA，U.S.A.)软件进行网络分析。这些基因利用生物芯片及iTRAQ蛋白质体分析所获得，并将上述基因进行网络分析。将基因登录号输入至IPA软件中，网络分析会利用目前已知的信息，显示各基因产物功能上的关系并将先关联的基因连结成网络。在62个由生物芯片鉴定出的基因，有42个基因落入3个网络群组中，网络主要功能分别为(1)癌症，细胞形态，及皮肤疾病及症状；(2)脂质代谢、小分子生化、分子的运送；(3)癌症，细胞移动、细胞生长及分化，如表3A所示。在之前蛋白质体研究中的39个蛋白质中有22个蛋白质落入另外3种群组中，网络主要功能分别为(1)癌症、细胞周期及细胞形态；(2)脂质代谢、小分子生化、组织损伤及不正常；(3)血液疾病、内分泌系统的分化及功能、神经系统的分化及功能，如表3B所示。表3A、3B列举网络的蛋白质功能及编号。于本发明所鉴定出来的基因以底线标示，此基因在先前肝脏的研究中皆未曾揭露。

实施例5：以人体临床证明由DMN诱导肝纤维化大鼠模式所鉴定出的生物标志

为了证明由DMN诱导肝纤维化大鼠模式所鉴定出的生物标志可用于治疗人类的肝纤维化及肝硬化，以Western Blotting分析人类血清中的碳酸酐酶1的表达(参照表2，序列编号：11及71)。取正常自愿者与B型肝炎的肝硬化病人的血清样本(每个病人取8μl)，先以ProteoPrep

20 PlamsaImmunodepletion试剂盒(Sigma-Aldrich，St.Louis，MO，U.S.A.)去除血清中存在量最多的前20种蛋白质。在移除后，将低含量的血清蛋白以5倍体积的冰丙酮于-20℃作用2小时沉淀。接着以12000rpm离心10分钟以获得蛋白质沉淀物。将此蛋白质沉淀物回溶，以12％的SDS-PAGE分离，并转渍至0.45μm的氟化氟亚乙烯(PVDF)膜(Millipore，Billerica，MA，U.S.A.)上。在以5％(w/v)的脱脂牛奶封阻后，以TBST缓冲液(20Mm Tris-HCl，pH 7.6，137mM NaCl，0.1％(v/v)Tween-20)清洗，且与对碳酸酐酶I(carbonic anhydrase I)具特异性的山羊多克隆抗体反应1小时。再以TBST缓冲液清洗氟化氟亚乙烯膜，并以辣根过氧化酶标定的驴抗山羊IgG(Jackson ImmunoResearchLaboratories，PA，U.S.A.)进行免疫染色。以增强式化学发光系统(ECL，Perkin-Elmer Life Sciences，Wellesley，MA.U.S.A.)检测上述免疫反应的条纹。Western Blotting的结果清楚显示一些肝硬化病人所获得的血清样本的第一型碳酸酐酶I浓度高于无肝硬化的正常人的血清样本。此结果证实由肝纤维化及肝硬化的大鼠模式所鉴定出来的生物标志与人类的肝纤维化及肝硬化有关。

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虽然本发明已以较佳实施例揭露如上，然其并非用以限定本发明，任何熟习此技艺者，在不脱离本发明的精神和范围内，当可作些许的更动与润饰，因此本发明的保护范围当视后附的申请专利范围所界定者为准。

序列表

<110>财团法人工业技术研究院

财团法人卫生研究院

HSIEH，HUI-CHU

TSENG，TZU-LING

SU，LI-JEN

HUANG，CHI-YING

HSU，SHIH-LAN

<120>包括肝纤维化和/或肝硬化的肝纤维损伤的生物标志及其检测方法

<130>09708.0003-00000

<140>

<141>

<150>60/761,959

<151>2006-01-24

<160>120

<170>PatentIn version 3.3

<210>1

<211>494

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<213>Rattus sp.

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Cys Leu Ser Leu Leu Ser Val Trp Thr Lys Leu Arg Thr Arg Gly Arg

20 25 30

Leu Pro Pro Gly Pro His Pro Pro Ser His Tyr Trp Glu Ser Thr Ala

35 40 45

Thr Glu Pro Gln Gly His Pro Ala Ser Leu Ser Lys Leu Ala Lys Glu

50 55 60

Tyr Gly Pro Val Tyr Thr Leu Tyr Phe Gly Thr Ser Pro Thr Val Val

65 70 75 80

Leu His Gly Tyr Asp Val Val Lys Glu Ala Leu Leu Gln Gln Gly Asp

85 90 95

Glu Phe Leu Gly Arg Gly Pro Leu Pro Ile Ile Glu Asp Thr His Lys

100 105 110

Gly Tyr Gly Leu Ile Phe Ser Asn Gly Glu Arg Trp Lys Val Met Arg

115 120 125

Arg Phe Ser Leu Met Thr Leu Arg Asn Phe Gly Met Gly Lys Arg Ser

130 135 140

Leu Glu Glu Arg Val Gln Glu Glu Ala Trp Cys Leu Val Glu Glu Leu

145 150 155 160

Gln Lys Thr Lys Ala Gln Pro Phe Asp Pro Thr Phe lle Leu Ala Cys

165 170 175

Ala Pro Cys Asn Val Ile Cys Ser Ile Leu Phe Asn Asp Arg Phe Gln

180 185 190

Tyr Asn Asp Lys Thr Phe Leu Asn Leu Met Asp Leu Leu Asn Lys Asn

195 200 205

Phe Gln Gln Val Asn Ser Val Trp Cys Gln Met Tyr Asn Leu Trp Pro

210 215 220

Thr Ile Ile Lys Tyr Leu Pro Gly Lys His Ile Glu Phe Ala Lys Arg

225 230 235 240

Ile Asp Asp Val Lys Asn Phe Ile Leu Glu Lys Val Lys Glu His Gln

245 250 255

Lys Ser Leu Asp Pro Ala Asn Pro Arg Asp Tyr Ile Asp Cys Phe Leu

260 265 270

Ser Lys Ile Glu Glu Glu Lys Asp Asn Leu Lys Ser Glu Phe His Leu

275 280 285

Glu Asn Leu Ala Val Cys Gly Ser Asn Leu Phe Thr Ala Gly Thr Glu

290 295 300

Thr Thr Ser Thr Thr Leu Arg Phe Gly Leu Leu Leu Leu Met Lys Tyr

305 310 315 320

Pro Glu Val Gln Ala Lys Val His Glu Glu Leu Asp Arg Val Ile Gly

325 330 335

Arg His Gln Pro Pro Ser Met Lys Asp Lys Met Lys Leu Pro Tyr Thr

340 345 350

Asp Ala Val Leu His Glu Ile Gln Arg Tyr Ile Thr Leu Val Gly Ser

355 360 365

Ser Leu Pro His Ala Val Val Gln Asp Thr Lys Phe Arg Asp Tyr Val

370 375 380

Ile Pro Lys Gly Thr Thr Val Leu Pro Met Leu Ser Ser Val Met Leu

385 390 395 400

Asp Gln Lys Glu Phe Ala Asn Pro Glu Lys Phe Asp Pro Gly His Phe

405 410 415

Leu Asp Lys Asn Gly Cys Phe Lys Lys Thr Asp Tyr Phe Val Pro Phe

420 425 430

Ser Leu Gly Lys Arg Ala Cys Val Gly Glu Ser Leu Ala Arg Met Glu

435 440 445

Leu Phe Leu Phe Phe Thr Thr Leu Leu Gln Lys Phe Ser Leu Lys Thr

450 455 460

Leu Val Glu Pro Lys Asp Leu Asp Ile Lys Pro Ile Thr Thr Gly Ile

465 470 475 480

Ile Asn Leu Pro Pro Pro Tyr Lys Leu Cys Leu Val Pro Arg

485 490

<210>2

<211>500

<212>PRT

<213>Rattus sp.

<400>2

Met Glu Leu Leu Ala Gly Thr Gly Leu Trp Pro Met Ala Ile Phe Thr

1 5 10 15

Val Ile Phe Ile Leu Leu Val Asp Leu Met His Arg Arg Gln Arg Trp

20 25 30

Thr Ser Arg Tyr Pro Pro Gly Pro Val Pro Trp Pro Val Leu Gly Asn

35 40 45

Leu Leu Gln Val Asp Leu Cys Asn Met Pro Tyr Ser Met Tyr Lys Leu

50 55 60

Gln Asn Arg Tyr Gly Asp Val Phe Ser Leu Gln Met Gly Trp Lys Pro

65 70 75 80

Val Val Val Ile Asn Gly Leu Lys Ala Val Gln Glu Leu Leu Val Thr

85 90 95

Cys Gly Glu Asp Thr Ala Asp Arg Pro Glu Met Pro Ile Phe Gln His

100 105 110

Ile Gly Tyr Gly His Lys Ala Lys Gly Val Val Leu Ala Pro Tyr Gly

115 120 125

Pro Glu Trp Arg Glu Gln Arg Arg Phe Ser Val Ser Thr Leu Arg Asn

130 135 140

Phe Gly Val Gly Lys Lys Ser Leu Glu Gln Trp Val Thr Asp Glu Ala

145 150 155 160

Ser His Leu Cys Asp Ala Leu Thr Ala Glu Ala Gly Arg Pro Leu Asp

165 170 175

Pro Tyr Thr Leu Leu Asn Lys Ala Val Cys Asn Val Ile Ala Ser Leu

180 185 190

Ile Tyr Ala Arg Arg Phe Asp Tyr Gly Asp Pro Asp Phe Ile Lys Val

195 200 205

Leu Lys Ile Leu Lys Glu Ser Met Gly Glu Gln Thr Gly Leu Phe Pro

210 215 220

Glu Val Leu Asn Met Phe Pro Val Leu Leu Arg Ile Pro Gly Leu Ala

225 230 235 240

Asp Lys Val Phe Pro Gly Gln Lys Thr Phe Leu Thr Met Val Asp Asn

245 250 255

Leu Val Thr Glu His Lys Lys Thr Trp Asp Pro Asp Gln Pro Pro Arg

260 265 270

Asp Leu Thr Asp Ala Phe Leu Ala Glu Ile Glu Lys Ala Lys Gly Asn

275 280 285

Pro Glu Ser Ser Phe Asn Asp Ala Asn Leu Arg Leu Val Val Asn Asp

290 295 300

Leu Phe Gly Ala Gly Met Val Thr Thr Ser Ile Thr Leu Thr Trp Ala

305 310 315 320

Leu Leu Leu Met Ile Leu His Pro Asp Val Gln Cys Arg Val Gln Gln

325 330 335

Glu Ile Asp Glu Val Ile Gly Gln Val Arg His Pro Glu Met Ala Asp

340 345 350

Gln Ala His Met Pro Phe Thr Asn Ala Val Ile His Glu Val Gln Arg

355 360 365

Phe Ala Asp Ile Val Pro Met Asn Leu Pro His Lys Thr Ser Arg Asp

370 375 380

Ile Glu Val Gln Gly Phe Leu Ile Pro Lys Gly Thr Thr Leu Ile Pro

385 390 395 400

Asn Leu Ser Ser Val Leu Lys Asp Glu Thr Val Trp Glu Lys Pro Leu

405 410 415

Arg Phe His Pro Glu His Phe Leu Asp Ala Gln Gly Asn Phe Val Lys

420 425 430

His Glu Ala Phe Met Pro Phe Ser Ala Gly Arg Arg Ala Cys Leu Gly

435 440 445

Glu Pro Leu Ala Arg Met Glu Leu Phe Leu Phe Phe Thr Cys Leu Leu

450 455 460

Gln Arg Phe Ser Phe Ser Val Pro Thr Gly Gln Pro Arg Pro Ser Asp

465 470 475 480

Tyr Gly Val Phe Ala Phe Leu Leu Ser Pro Ser Pro Tyr Gln Leu Cys

485 490 495

Ala Phe Lys Arg

500

<210>3

<211>2505

<212>PRT

<213>Rattus sp.

<400>3

Met Glu Glu Val Val Ile Ala Gly Met Ser Gly Lys Leu Pro Glu Ser

1 5 10 15

Glu Asn Leu Gln Glu Phe Trp Ala Asn Leu Ile Gly Gly Val Asp Met

20 25 30

Val Thr Asp Asp Asp Arg Arg Trp Lys Ala Gly Leu Tyr Gly Leu Pro

35 40 45

Lys Arg Ser Gly Lys Leu Lys Asp Leu Ser Lys Phe Asp Ala Ser Phe

50 55 60

Phe Gly Val His Pro Lys Gln Ala His Thr Met Asp Pro Gln Leu Arg

65 70 75 80

Leu Leu Leu Glu Val Ser Tyr Glu Ala Ile Val Asp Gly Gly Ile Asn

85 90 95

Pro Ala Ser Leu Arg Gly Thr Asn Thr Gly Val Trp Val Gly Val Ser

100 105 110

Gly Ser Glu Ala Ser Glu Ala Leu Ser Arg Asp Pro Glu Thr Leu Leu

115 120 125

Gly Tyr Ser Met Val Gly Cys Gln Arg Ala Met Met Ala Asn Arg Leu

130 135 140

Ser Phe Phe Phe Asp Phe Lys Gly Pro Ser Ile Ala Leu Asp Thr Ala

145 150 155 160

Cys Ser Ser Ser Leu Leu Ala Leu Gln Asn Ala Tyr Gln Ala Ile Arg

165 170 175

Ser Gly Glu Cys Pro Ala Ala Ile Val Gly Gly Ile Asn Leu Leu Leu

180 185 190

Lys Pro Asn Thr Ser Val Gln Phe Met Lys Leu Gly Met Leu Ser Pro

195 200 205

Asp Gly Thr Cys Arg Ser Phe Asp Asp Ser Gly Asn Gly Tyr Cys Arg

210 215 220

Ala Glu Ala Val Val Ala Val Leu Leu Thr Lys Lys Ser Leu Ala Arg

225 230 235 240

Arg Val Tyr Ala Thr Ile Leu Asn Ala Gly Thr Asn Thr Asp Gly Cys

245 250 255

Lys Glu Gln Gly Val Thr Phe Pro Ser Gly Glu Ala Gln Glu Gln Leu

260 265 270

Ile Arg Ser Leu Tyr Gln Pro Gly Gly Val Ala Pro Glu Ser Leu Glu

275 280 285

Tyr Ile Glu Ala His Gly Thr Gly Thr Lys Val Gly Asp Pro Gln Glu

290 295 300

Leu Asn Gly Ile Thr Arg Ser Leu Cys Ala Phe Arg Gln Ser Pro Leu

305 310 315 320

Leu Ile Gly Ser Thr Lys Ser Asn Met Gly His Pro Glu Pro Ala Ser

325 330 335

Gly Leu Ala Ala Leu Thr Lys Val Leu Leu Ser Leu Glu Asn Gly Val

340 345 350

Trp Ala Pro Asn Leu His Phe His Asn Pro Asn Pro Glu Ile Pro Ala

355 360 365

Leu Leu Asp Gly Arg Leu Gln Val Val Asp Arg Pro Leu Pro Val Arg

370 375 380

Gly Gly Ile Val Gly Ile Asn Ser Phe Gly Phe Gly Gly Ala Asn Val

385 390 395 400

His Val Ile Leu Gln Pro Asn Thr Gln Gln Ala Pro Ala Pro Ala Pro

405 410 415

His Ala Ala Leu Pro His Leu Leu His Ala Ser Gly Arg Thr Met Glu

420 425 430

Ala Val Gln Gly Leu Leu Glu Gln Gly Arg Gln His Ser Gln Asp Leu

435 440 445

Ala Phe Val Ser Met Leu Asn Asp Ile Ala Ala Thr Pro Thr Ala Ala

450 455 460

Met Pro Phe Arg Gly Tyr Thr Val Leu Gly Val Glu Gly His Val Gln

465 470 475 480

Glu Val Gln Gln Val Pro Ala Ser Gln Arg Pro Leu Trp Phe Ile Cys

485 490 495

Ser Gly Met Gly Thr Gln Trp Arg Gly Met Gly Leu Ser Leu Met Arg

500 505 510

Leu Asp Ser Phe Arg Glu Ser Ile Leu Arg Ser Asp Glu Ala Leu Lys

515 520 525

Pro Leu Gly Val Lys Val Ser Asp Leu Leu Leu Ser Thr Asp Glu His

530 535 540

Thr Phe Asp Asp Ile Val His Ser Phe Val Ser Leu Thr Ala Ile Gln

545 550 555 560

Ile Ala Leu Ile Asp Leu Leu Thr Ser Met Gly Leu Lys Pro Asp Gly

565 570 575

Ile Ile Gly His Ser Leu Gly Glu Val Ala Cys Gly Tyr Ala Asp Gly

580 585 590

Cys Leu Ser Gln Arg Glu Ala Val Leu Ala Ala Tyr Trp Arg Gly Gln

595 600 605

Cys Ile Lys Asp Ala Asn Leu Pro Ala Gly Ser Met Ala Ala Val Gly

610 615 620

Leu Ser Trp Glu Glu Cys Lys Gln Arg Cys Pro Pro Gly Val Val Pro

625 630 635 640

Ala Cys His Asn Ser Glu Asp Thr Val Thr Ile Ser Gly Pro Gln Ala

645 650 655

Ala Val Asn Glu Phe Val Glu Gln Leu Lys Gln Glu Gly Val Phe Ala

660 665 670

Lys Glu Val Arg Thr Gly Gly Leu Ala Phe His Ser Tyr Phe Met Glu

675 680 685

Gly Ile Ala Pro Thr Leu Leu Gln Ala Leu Lys Lys Val Ile Arg Glu

690 695 700

Pro Arg Pro Arg Ser Ala Arg Trp Leu Ser Thr Ser Ile Pro Glu Ala

705 710 715 720

Gln Trp Gln Ser Ser Leu Ala Arg Thr Ser Ser Ala Glu Tyr Asn Val

725 730 735

Asn Asn Leu Val Ser Pro Val Leu Phe Gln Glu Ala Leu Trp His Val

740 745 750

Pro Glu His Ala Val Val Leu Glu Ile Ala Pro His Ala Leu Leu Gln

755 760 765

Ala Val Leu Lys Arg Gly Val Lys Pro Ser Cys Thr Ile Ile Pro Leu

770 775 780

Met Lys Arg Asp His Lys Asp Asn Leu Glu Phe Phe Leu Thr Asn Leu

785 790 795 800

Gly Lys Val His Leu Thr Gly Ile Asp Ile Asn Pro Asn Ala Leu Phe

805 810 815

Pro Pro Val Glu Phe Pro Val Pro Arg Gly Thr Pro Leu Ile Ser Pro

820 825 830

His Ile Lys Trp Asp His Ser Gln Thr Trp Asp Ile Pro Val Ala Glu

835 840 845

Asp Phe Pro Asn Gly Ser Ser Ser Ser Ser Ala Thr Val Tyr Asn Ile

850 855 860

Asp Ala Ser Ser Glu Ser Ser Asp His Tyr Leu Val Asp His Cys Ile

865 870 875 880

Asp Gly Arg Val Leu Phe Pro Gly Thr Gly Tyr Leu Tyr Leu Val Trp

885 890 895

Lys Thr Leu Ala Arg Ser Leu Ser Leu Ser Leu Glu Glu Thr Pro Val

900 905 910

Val Phe Glu Asn Val Thr Phe His Gln Ala Thr Ile Leu Pro Arg Thr

915 920 925

Gly Thr Val Pro Leu Glu Val Arg Leu Leu Glu Ala Ser His Ala Phe

930 935 940

Glu Val Ser Asp Ser Gly Asn Leu Ile Val Ser Gly Lys Val Tyr Gln

945 950 955 960

Trp Glu Asp Pro Asp Ser Lys Leu Phe Asp His Pro Glu Val Pro Ile

965 970 975

Pro Ala Glu Ser Glu Ser Val Ser Arg Leu Thr Gln Gly Glu Val Tyr

980 985 990

Lys Glu Leu Arg Leu Arg Gly Tyr Asp Tyr Gly Pro His Phe Gln Gly

995 1000 1005

Val Tyr Glu Ala Thr Leu Glu Gly Glu Gln Gly Lys Leu Leu Trp

1010 1015 1020

Lys Asp Asn Trp Val Thr Phe Met Asp Thr Met Leu Gln Ile Ser

1025 1030 1035

Ile Leu Gly Phe Ser Lys Gln Ser Leu Gln Leu Pro Thr Arg Val

1040 1045 1050

Thr Ala Ile Tyr Ile Asp Pro Ala Thr His Leu Gln Lys Val Tyr

1055 1060 1065

Met Leu Glu Gly Asp Thr Gln Val Ala Asp Val Thr Thr Ser Arg

1070 1075 1080

Cys Leu Gly Val Thr Val Ser Gly Gly Val Tyr Ile Ser Arg Leu

1085 1090 1095

Gln Thr Thr Ala Thr Ser Arg Arg Gln Gln Glu Gln Leu Val Pro

1100 1105 1110

Thr Leu Glu Lys Phe Val Phe Thr Pro His Val Glu Pro Glu Cys

1115 1120 1125

Leu Ser Glu Ser Ala Ile Leu Gln Lys Glu Leu Gln Leu Cys Lys

1130 1135 1140

Gly Leu Ala Lys Ala Leu Gln Thr Lys Ala Thr Gln Gln Gly Leu

1145 1150 1155

Lys Met Thr Val Pro Gly Leu Glu Asp Leu Pro Gln His Gly Leu

1160 1165 1170

Pro Arg Leu Leu Ala Ala Ala Cys Gln Leu Gln Leu Asn Gly Asn

1175 1180 1185

Leu Gln Leu Glu Leu Gly Glu Val Leu Ala Arg Glu Arg Leu Leu

1190 1195 1200

Leu Pro Glu Asp Pro Leu Ile Ser Gly Leu Leu Asn Ser Gln Ala

1205 1210 1215

Leu Lys Ala Cys Ile Asp Thr Ala Leu Glu Asn Leu Ser Thr Leu

1220 1225 1230

Lys Met Lys Val Val Glu Val Leu Ala Gly Glu Gly His Leu Tyr

1235 1240 1245

Ser His Ile Ser Ala Leu Leu Asn Thr Gln Pro Met Leu Gln Leu

1250 1255 1260

Glu Tyr Thr Ala Thr Asp Arg His Pro Gln Ala Leu Lys Asp Val

1265 1270 1275

Gln Thr Lys Leu Gln Gln His Asp Val Ala Gln Gly Gln Trp Asp

1280 1285 1290

Pro Ser Gly Pro Ala Pro Thr Asn Leu Gly Ala Leu Asp Leu Val

1295 1300 1305

Val Cys Asn Cys Ala Leu Ala Thr Leu Gly Asp Pro Ala Leu Ala

1310 1315 1320

Leu Asp Asn Met Val Ala Ala Leu Lys Asp Gly Gly Phe Leu Leu

1325 1330 1335

Met His Thr Val Leu Lys Gly His Ala Leu Gly Glu Thr Leu Ala

1340 1345 1350

Cys Leu Pro Ser Glu Val Gln Pro Gly Pro Ser Phe Leu Ser Gln

1355 1360 1365

Glu Glu Trp Glu Ser Leu Phe Ser Arg Lys Ala Leu His Leu Val

1370 1375 1380

Gly Leu Lys Lys Ser Phe Tyr Gly Thr Ala Leu Phe Leu Cys Arg

1385 1390 1395

Arg Leu Ser Pro Gln Asp Lys Pro Ile Phe Leu Pro Val Glu Asp

1400 1405 1410

Thr Ser Phe Gln Trp Val Asp Ser Leu Lys Ser Ile Leu Ala Thr

1415 1420 1425

Ser Ser Ser Gln Pro Val Trp Leu Thr Ala Met Asn Cys Pro Thr

1430 1435 1440

Ser Gly Val Val Gly Leu Val Asn Cys Leu Arg Lys Glu Pro Gly

1445 1450 1455

Gly His Arg Ile Arg Cys Ile Leu Leu Ser Asn Leu Ser Ser Thr

1460 1465 1470

Ser His Val Pro Lys Leu Asp Pro Gly Ser Ser Glu Leu Gln Lys

1475 1480 1485

Val Leu Glu Ser Asp Leu Val Met Asn Val Tyr Arg Asp Gly Ala

1490 1495 1500

Trp Gly Ala Phe Arg His Phe Gln Leu Glu Gln Asp Lys Pro Glu

1505 1510 1515

Glu Gln Thr Ala His Ala Phe Val Asn Val Leu Thr Arg Gly Asp

1520 1525 1530

Leu Ala Ser Ile Arg Trp Val Ser Ser Pro Leu Lys His Met Gln

1535 1540 1545

Pro Pro Ser Ser Ser Gly Ala Gln Leu Cys Thr Val Tyr Tyr Ala

1550 1555 1560

Ser Leu Asn Phe Arg Asp Ile Met Leu Ala Thr Gly Lys Leu Ser

1565 1570 1575

Pro Asp Ala Ile Pro Gly Lys Trp Ala Ser Arg Asp Cys Met Leu

1580 1585 1590

Gly Met Glu Phe Ser Gly Arg Asp Lys Cys Gly Arg Arg Val Met

1595 1600 1605

Gly Leu Val Pro Ala Glu Gly Leu Ala Thr Ser Val Leu Leu Ser

1610 1615 1620

Pro Asp Phe Leu Trp Asp Val Pro Ser Ser Trp Thr Leu Glu Glu

1625 1630 1635

Ala Ala Ser Val Pro Val Val Tyr Thr Thr Ala Tyr Tyr Ser Leu

1640 1645 1650

Val Val Arg Gly Arg Ile Gln His Gly Glu Thr Val Leu Ile His

1655 1660 1665

Ser Gly Ser Gly Gly Val Gly Gln Ala Ala Ile Ser Ile Ala Leu

1670 1675 1680

Ser Leu Gly Cys Arg Val Phe Thr Thr Val Gly Ser Ala Glu Lys

1685 1690 1695

Arg Ala Tyr Leu Gln Ala Arg Phe Pro Gln Leu Asp Asp Thr Ser

1700 1705 1710

Phe Ala Asn Ser Arg Asp Thr Ser Phe Glu Gln His Val Leu Leu

1715 1720 1725

His Thr Gly Gly Lys Gly Val Asp Leu Val Leu Asn Ser Leu Ala

1730 1735 1740

Glu Glu Lys Leu Gln Ala Ser Val Arg Cys Leu Ala Gln His Gly

1745 1750 1755

Arg Phe Leu Glu Ile Gly Lys Phe Asp Leu Ser Asn Asn His Pro

1760 1765 1770

Leu Gly Met Ala Ile Phe Leu Lys Asn Val Thr Phe His Gly Ile

1775 1780 1785

Leu Leu Asp Ala Leu Phe Glu Gly Ala Asn Asp Ser Trp Arg Glu

1790 1795 1800

Val Ala Glu Leu Leu Lys Ala Gly Ile Arg Asp Gly Val Val Lys

1805 1810 1815

Pro Leu Lys Cys Thr Val Phe Pro Lys Ala Gln Val Glu Asp Ala

1820 1825 1830

Phe Arg Tyr Met Ala Gln Gly Lys His Ile Gly Lys Val Leu Val

1835 1840 1845

Gln Val Arg Glu Glu Glu Pro Glu Ala Met Leu Pro Gly Ala Gln

1850 1855 1860

Pro Thr Leu Ile Ser Ala Ile Ser Lys Thr Phe Cys Pro Glu His

1865 1870 1875

Lys Ser Tyr Ile Ile Thr Gly Gly Leu Gly Gly Phe Gly Leu Glu

1880 1885 1890

Leu Ala Arg Trp Leu Val Leu Arg Gly Ala Gln Arg Leu Val Leu

1895 1900 1905

Thr Ser Arg Ser Gly Ile Arg Thr Gly Tyr Gln Ala Lys His Val

1910 1915 1920

Arg Glu Trp Arg Arg Gln Gly Ile His Val Leu Val Ser Thr Ser

1925 1930 1935

Asn Val Ser Ser Leu Glu Gly Ala Arg Ala Leu Ile Ala Glu Ala

1940 1945 1950

Thr Lys Leu Gly Pro Val Gly Gly Val Phe Asn Leu Ala Met Val

1955 1960 1965

Leu Arg Asp Ala Met Leu Glu Asn Gln Thr Pro Glu Leu Phe Gln

1970 1975 1980

Asp Val Asn Lys Pro Lys Tyr Asn Gly Thr Leu Asn Leu Asp Arg

1985 1990 1995

Ala Thr Arg Glu Ala Cys Pro Glu Leu Asp Tyr Phe Val Ala Phe

2000 2005 2010

Ser Ser Val Ser Cys Gly Arg Gly Asn Ala Gly Gln Ser Asn Tyr

2015 2020 2025

Gly Phe Ala Asn Ser Thr Met Glu Arg Ile Cys Glu Gln Arg Arg

2030 2035 2040

His Asp Gly Leu Pro Gly Leu Ala Val Gln Trp Gly Ala Ile Gly

2045 2050 2055

Asp Val Gly Ile Ile Leu Glu Ala Met Gly Thr Asn Asp Thr Val

2060 2065 2070

Val Gly Gly Thr Leu Pro Gln Arg Ile Ser Ser Cys Met Glu Val

2075 2080 2085

Leu Asp Leu Phe Leu Asn Gln Pro His Ala Val Leu Ser Ser Phe

2090 2095 2100

Val Leu Val Glu Lys Lys Ala Val Ala His Gly Asp Gly Glu Ala

2105 2110 2115

Gln Arg Asp Leu Val Lys Ala Val Ala His Ile Leu Gly Ile Arg

2120 2125 2130

Asp Leu Ala Gly Ile Asn Leu Asp Ser Ser Leu Ala Asp Leu Gly

2135 2140 2145

Leu Asp Ser Leu Met Gly Val Glu Val Arg Gln Ile Leu Glu Arg

2150 2155 2160

Glu His Asp Leu Val Leu Pro Ile Arg Glu Val Arg Gln Leu Thr

2165 2170 2175

Leu Arg Lys Leu Gln Glu Met Ser Ser Lys Ala Gly Ser Asp Thr

2180 2185 2190

Glu Leu Ala Ala Pro Lys Ser Lys Asn Asp Thr Ser Leu Lys Gln

2195 2200 2205

Ala Gln Leu Asn Leu Ser Ile Leu Leu Val Asn Pro Glu Gly Pro

2210 2215 2220

Thr Leu Thr Arg Leu Asn Ser Val Gln Ser Ser Glu Arg Pro Leu

2225 2230 2235

Phe Leu Val His Pro Ile Glu Gly Ser Ile Thr Val Phe His Ser

2240 2245 2250

Leu Ala Ala Lys Leu Ser Val Pro Thr Tyr Gly Leu Gln Cys Thr

2255 2260 2265

Gln Ala Ala Pro Leu Asp Ser Ile Pro Asn Leu Ala Ala Tyr Tyr

2270 2275 2280

Ile Asp Cys Ile Lys Gln Val Gln Pro Glu Gly Pro His Arg Val

2285 2290 2295

Ala Gly Tyr Ser Phe Gly Ala Cys Val Ala Phe Glu Met Cys Ser

2300 2305 2310

Gln Leu Gln Ala Gln Gln Gly Pro Ala Pro Ala His Asn Asn Leu

2315 2320 2325

Phe Leu Phe Asp Gly Ser His Thr Tyr Val Leu Ala Tyr Thr Gln

2330 2335 2340

Ser Tyr Arg Ala Lys Leu Thr Pro Gly Cys Glu Ala Glu Ala Glu

2345 2350 2355

Ala Glu Ala Ile Cys Phe Phe Ile Lys Gln Phe Val Asp Ala Glu

2360 2365 2370

His Ser Lys Val Leu Glu Ala Leu Leu Pro Leu Lys Ser Leu Glu

2375 2380 2385

Asp Arg Val Ala Ala Ala Val Asp Leu Ile Thr Arg Ser His Gln

2390 2395 2400

Ser Leu Asp Arg Arg Asp Leu Ser Phe Ala Ala Val Ser Phe Tyr

2405 2410 2415

Tyr Lys Leu Arg Ala Ala Asp Gln Tyr Lys Pro Lys Ala Lys Tyr

2420 2425 2430

His Gly Asn Val Ile Leu Leu Arg Ala Lys Thr Gly Gly Thr Tyr

2435 2440 2445

Gly Glu Asp Leu Gly Ala Asp Tyr Asn Leu Ser Gln Val Cys Asp

2450 2455 2460

Gly Lys Val Ser Val His Ile Ile Glu Gly Asp His Arg Thr Leu

2465 2470 2475

Leu Glu Gly Arg Gly Leu Glu Ser Ile Ile Asn Ile Ile His Ser

2480 2485 2490

Ser Leu Ala Glu Pro Arg Val Ser Val Arg Glu Gly

2495 2500 2505

<210>4

<211>381

<212>PRT

<213>Rattus sp.

<400>4

Met Asn Pro Phe Ser Ser Glu Ser Ala Trp Leu Cys Leu Thr Ala Thr

1 5 10 15

Ala Val Leu Gly Gly Met Leu Leu Cys Lys Ala Trp Ser Ser Gly Gln

20 25 30

Leu Arg Ser Gln Val Val Cys Leu Ala Gly Leu Trp Gly Gly Ala Cys

35 40 45

Leu Leu Ser Leu Ser Leu Leu Cys Ser Leu Phe Leu Leu Ser Val Ser

50 55 60

Cys Phe Phe Leu Leu Tyr Val Ser Ser Ser Asp Gln Asp Leu Leu Pro

65 70 75 80

Val Asp Gln Lys Ala Val Leu Val Thr Gly Ala Asp Ser Gly Phe Gly

85 90 95

His Ala Leu Ala Lys His Leu Asp Lys Leu Gly Phe Thr Val Phe Ala

100 105 110

Gly Val Leu Asp Lys Glu Gly Pro Gly Ala Glu Glu Leu Arg Lys Asn

115 120 125

Cys Ser Glu Arg Leu Ser Val Leu Gln Met Asp Val Thr Lys Pro Glu

130 135 140

Gln Ile Lys Asp Val His Ser Glu Val Ala Glu Lys Ile Gln Asp Lys

145 150 155 160

Gly Leu Trp Ala Val Val Asn Asn Ala Gly Val Leu His Phe Pro Ile

165 170 175

Asp Gly Glu Leu Ile Pro Met Thr Val Tyr Arg Lys Cys Met Ala Val

180 185 190

Asn Phe Phe Gly Ala Val Glu Val Thr Lys Val Phe Leu Pro Leu Leu

195 200 205

Arg Lys Ser Lys Gly Arg Leu Val Asn Val Ser Ser Met Gly Ala Met

210 215 220

Ile Pro Phe Gln Met Val Ala Ala Tyr Ala Ser Thr Lys Ala Ala Ile

225 230 235 240

Ser Met Phe Ser Ala Val Ile Arg Gln Glu Leu Ala Lys Trp Gly Val

245 250 255

Lys Val Val Thr Ile His Pro Gly Gly Phe Gln Thr Asn Ile Val Gly

260 265 270

Ser Gln Asp Ser Trp Asp Lys Met Glu Lys Glu Ile Leu Asp His Phe

275 280 285

Ser Lys Glu Ile Gln Glu Asn Tyr Gly Gln Glu Tyr Val His Thr Gln

290 295 300

Lys Leu Ala Leu Pro Val Met Arg Glu Met Ser Asn Pro Asp Ile Thr

305 310 315 320

Pro Val Leu Arg Asp Ile Gln His Ala Ile Cys Ala Lys Asn Pro Ser

325 330 335

Ser Phe Tyr Cys Ser Gly Arg Met Thr Tyr Leu Trp Ile Cys Phe Ala

340 345 350

Ala Tyr Ser Pro Ile Ser Leu Leu Asp Tyr Ile Leu Lys Asn Tyr Phe

355 360 365

Thr Pro Lys Leu Met Pro Arg Ala Leu Arg Thr Ala Ser

370 375 380

<210>5

<211>295

<212>PRT

<213>Rattus sp.

<400>5

Met Glu Thr Ser Met Pro Glu Tyr Tyr Glu Val Phe Gly Asp Phe His

1 5 10 15

Gly Phe Leu Met Asp Lys Leu Phe Thr Lys Tyr Trp Glu Asp Val Glu

20 25 30

Thr Phe Ser Ala Arg Pro Asp Asp Leu Leu Val Val Thr Tyr Pro Lys

35 40 45

Ser Gly Ser Thr Trp Ile Gly Glu Ile Val Asp Met Ile Tyr Lys Glu

50 55 60

Gly Asp Val Glu Lys Cys Lys Glu Asp Ala Ile Phe Asn Arg Ile Pro

65 70 75 80

Tyr Leu Glu Cys Arg Asn Glu Asp Leu Ile Asn Gly Ile Lys Gln Leu

85 90 95

Lys Glu Lys Glu Ser Pro Arg Ile Val Lys Thr His Leu Pro Ala Lys

100 105 110

Leu Leu Pro Ala Ser Phe Trp Glu Lys Asn Cys Lys Ile Ile Tyr Leu

115 120 125

Cys Arg Asn Ala Lys Asp Val Val Val Ser Tyr Tyr Tyr Phe Phe Leu

130 135 140

Ile Met Lys Ser Tyr Pro Asn Pro Lys Ser Phe Ser Glu Phe Val Glu

145 150 155 160

Lys Phe Met Glu Gly Gln Val Pro Tyr Gly Ser Trp Tyr Asp His Val

165 170 175

Lys Ser Trp Trp Glu Lys Ser Lys Asn Ser Arg Val Leu Phe Met Phe

180 185 190

Tyr Glu Asp Met Lys Glu Asp Ile Arg Arg Glu Val Val Lys Leu Ile

195 200 205

Glu Phe Leu Glu Arg Asp Pro Ser Ala Glu Leu Val Asp Arg Ile Ile

210 215 220

Gln His Thr Ser Phe Gln Glu Met Lys Asn Asn Pro Cys Thr Asn Tyr

225 230 235 240

Ser Met Leu Pro Glu Thr Met Ile Asp Leu Lys Val Ser Pro Phe Met

245 250 255

Arg Lys Gly Ile Val Gly Asp Trp Lys Asn His Phe Pro Glu Ala Leu

260 265 270

Arg Glu Arg Phe Glu Glu His Tyr Gln Gln Gln Met Lys Asp Cys Pro

275 280 285

Val Lys Phe Arg Ala Glu Leu

290 295

<210>6

<211>1585

<212>PRT

<213>Rattus sp.

<400>6

Met Ser Ser Leu Gln Glu Leu Cys Ser Gly Leu Pro Leu Arg Pro Leu

1 5 10 15

Pro Glu Asn Arg Gly Arg Trp Ala Gly Val Pro His Ala Pro Val Arg

20 25 30

Thr Pro Asp Leu Ser Pro Glu Glu Glu Gln Leu Ala Leu Arg Asn Ala

35 40 45

Leu Arg Tyr Phe Pro Pro Asp Val Gln Lys Leu Leu Ala Leu Glu Phe

50 55 60

Ala Gln Glu Leu Arg Gln Phe Gly His Ile Tyr Met Tyr Arg Phe Cys

65 70 75 80

Pro Ser Ile Glu Met Arg Ala Tyr Pro Ile Glu Gln Tyr Pro Cys Arg

85 90 95

Thr Arg Ala Ala Ala Ala Ile Met His Met Ile Met Asn Asn Leu Asp

100 105 110

Pro Ala Val Ala Gln Phe Pro Gln Glu Leu Val Thr Tyr Gly Gly Asn

115 120 125

Gly Gln Val Phe Ser Asn Trp Ala Gln Val Trp Val Gln Gly Ala Ser

130 135 140

Ser His Leu Gln Ser Pro Pro Cys Ala Leu Ser Ile Gln Phe Trp Leu

145 150 155 160

Thr Met Ser Tyr Leu Ser Lys Met Thr Glu Glu Gln Thr Leu Val Met

165 170 175

Tyr Ser Gly His Pro Leu Gly Leu Phe Pro Ser Ser Ser His Ala Pro

180 185 190

Arg Leu Val Ile Thr Asn Gly Met Val Ile Pro Asn Tyr Ser Ser Arg

195 200 205

Thr Glu Tyr Glu Lys Leu Phe Ala Leu Gly Val Thr Met Tyr Gly Gln

210 215 220

Met Thr Ala Gly Ser Tyr Cys Tyr Ile Gly Pro Gln Gly Ile Val His

225 230 235 240

Gly Thr Val Leu Thr Val Leu Asn Ala Gly Arg Arg Tyr Leu Gly Ile

245 250 255

Glu Asp Leu Ala Gly Lys Val Phe Val Thr Ser Gly Leu Gly Gly Met

260 265 270

Ser Gly Ala Gln Ala Lys Ala Ala Val Ile Val Gly Cys Ile Gly Val

275 280 285

Ile Ala Glu Val Asp Lys Ala Ala Leu Val Lys Arg His Gln Gln Gly

290 295 300

Trp Leu Met Glu Val Thr Asp Ser Leu Asp His Cys Ile Ala Arg Leu

305 310 315 320

Arg Glu Ala Arg Lys Lys Lys Glu Val Leu Ser Leu Gly Tyr His Gly

325 330 335

Asn Val Val Asp Leu Trp Glu Arg Leu Val His Glu Leu Asp Thr Thr

340 345 350

Gly Glu Leu Leu Val Asp Leu Gly Ser Asp Gln Thr Ser Cys His Asn

355 360 365

Pro Phe Asn Gly Gly Tyr Tyr Pro Val Gln Leu Ser Phe Ser Glu Ala

370 375 380

Gln Ser Leu Met Ser Ser Asn Pro Ala Ala Phe Lys Asn Leu Val Gln

385 390 395 400

Glu Ser Leu Arg Arg His Ile Ser Ala Ile Asn Arg Leu Ala Gln Glu

405 410 415

Lys Phe Phe Phe Trp Asp Tyr Gly Asn Ala Phe Leu Leu Glu Ala Gln

420 425 430

Arg Ala Gly Ala Asp Val Glu Lys Lys Gly Ala Asn Lys Thr Glu Phe

435 440 445

Arg Tyr Pro Ser Tyr Val Gln His Ile Met Gly Asp Ile Phe Ser Gln

450 455 460

Gly Phe Gly Pro Phe Arg Trp Val Cys Thr Ser Gly Asn Pro Gln Asp

465 470 475 480

Leu Thr Val Thr Asp His Leu Ala Thr Ser Val Leu Glu Lys Ala Ile

485 490 495

Ala Asp Gly Gly Asp Thr Ser Gly Trp Val Val Leu Arg Ser Asp Ser

500 505 510

Cys Phe Cys Gly Ala Leu Gly Gly Leu Cys Gln Ile Leu Gln Glu Ser

515 520 525

Lys Asp His Arg Leu Leu His Lys Gly Thr Ser Ser Thr Phe Arg Ser

530 535 540

His Ser Leu Lys Ala Val Leu Met Lys Ala Ser Val Lys Leu Gln Tyr

545 550 555 560

Met Asp Asn Ile Arg Trp Ile Arg Glu Ala Ala Lys His Gln Leu Val

565 570 575

Val Gly Ser Gln Ala Arg Ile Leu Tyr Ser Asp Gln Lys Gly Arg Val

580 585 590

Ala Ile Ala Val Ala Ile Asn Gln Ala Ile Ala Ser Gly Lys Ile Lys

595 600 605

Ala Pro Val Val Leu Ser Arg Asp His His Asp Val Ser Gly Thr Asp

610 615 620

Ser Pro Phe Arg Glu Thr Ser Asn Ile Tyr Asp Gly Ser Ala Phe Cys

625 630 635 640

Ala Asp Met Ala Val Gln Asn Phe Val Gly Asp Ala Cys Arg Gly Ala

645 650 655

Thr Trp Val Ala Leu His Asn Gly Gly Gly Val Gly Trp Gly Glu Val

660 665 670

Ile Asn Gly Gly Phe Gly Leu Val Leu Asp Gly Thr Pro Glu Ala Glu

675 680 685

Gln Lys Ala Arg Met Met Leu Ser Trp Asp Val Ser Asn Gly Val Ala

690 695 700

Arg Arg Cys Trp Ser Gly Asn Pro Lys Ala Tyr Glu Ile Ile Cys Gln

705 710 715 720

Thr Met His Asp Asn Ser Gly Leu Val Val Thr Leu Pro His Glu Val

725 730 735

Ala Asp Glu Gln Val Leu Arg Gln Asp Leu Leu Gln Gly Lys Pro Gly

740 745 750

Leu Arg Ala Leu Gln Arg Gly His Arg Glu Asp Glu Lys Gln Ser Arg

755 760 765

Glu Val Gln Ser Leu Ser Ala Ser Ser Gly Pro Cys Asp Arg Arg Leu

770 775 780

Gly Leu Lys Ala Lys His Ser Gln Leu Gly Gly Pro Ala Pro Ala Pro

785 790 795 800

Pro Pro Gly Ser Leu Val Thr Thr Val Pro Thr Ala Leu Ala Arg His

805 810 815

Ala His Ala His Gly Pro Arg Ala Arg Ala Ala Arg Asp Ala Thr Leu

820 825 830

Gly Cys Thr Leu Arg Leu Ala Leu Thr Glu Thr Pro Gly Gly Arg Thr

835 840 845

Leu Gly Val Ala Arg Met Pro Gly Arg Ala Gly Pro Leu Phe Ser Gly

850 855 860

Gly Cys Gly Ser Asp Ala Ser Ala Gly Pro Lys Met Asp Leu Pro Ala

865 870 875 880

Val Leu Ala Ala Pro Ala Thr Arg Gly Asp Gln His Gly Gly Gly Pro

885 890 895

Ser Arg Leu Arg Arg Gly Thr Gly Pro Ser Leu Gly Ala Gly Pro Gly

900 905 910

Arg Arg Arg Leu Leu Leu Leu Arg Ser Pro Glu Asp Gly Gly Pro Gly

915 920 925

Pro Arg Gln Glu Glu Ala Pro Gly Pro Ser Pro Pro Pro Pro Glu Asp

930 935 940

Gly Gly Asp Ser Phe Val Val Leu Leu Glu Val Pro Arg Ala Ala Asp

945 950 955 960

Thr His Glu Gln Glu Glu Thr Glu Pro Asp Ser Gly Ala Ser Pro Thr

965 970 975

Glu Gln Val Pro Ala Ala Ala Pro Gly Ala Ala Leu Ala Gly Thr Val

980 985 990

Thr Ile His Asn Gln Asp Leu Leu Val Arg Phe Asp Arg Gly Val Phe

995 1000 1005

Thr Leu Ala Ala Ala Pro Ala Pro Ala Thr Gln Gly Leu His Pro

1010 1015 1020

Ala Thr Thr Pro Gly Leu Glu Pro Ser Ser Ala Ala Ala Ser Arg

1025 1030 1035

Arg Gly Pro Val Ala Ala Ser Ala Gly Ser Pro Ala Tyr Arg Cys

1040 1045 1050

Pro Glu Pro Gln Cys Ala Leu Ser Phe Ala Lys Lys His Gln Leu

1055 1060 1065

Lys Val His Leu Leu Thr His Gly Ser Leu Gln Gly Arg Arg Pro

1070 1075 1080

Phe Lys Cys Pro Leu Asp Gly Cys Gly Trp Ala Phe Thr Thr Ser

1085 1090 1095

Tyr Lys Leu Lys Arg His Leu Gln Ser His Asp Lys Leu Arg Pro

1100 1105 1110

Phe Ser Cys Pro Val Gly Gly Cys Gly Lys Lys Phe Thr Thr Val

1115 1120 1125

Tyr Asn Leu Lys Ala His Met Lys Gly His Glu Gln Glu Ser Leu

1130 1135 1140

Phe Lys Cys Glu Val Cys Ala Glu Arg Phe Pro Thr His Ala Lys

1145 1150 1155

Leu Asn Ser His Gln Arg Ser His Phe Glu Pro Glu Arg Pro Tyr

1160 1165 1170

Lys Cys Asp Phe Pro Gly Cys Glu Lys Thr Phe Ile Thr Val Ser

1175 1180 1185

Ala Leu Phe Ser His Asn Arg Ala His Phe Arg Glu Gln Glu Leu

1190 1195 1200

Phe Ser Cys Ser Phe Pro Gly Cys Asn Lys Gln Tyr Asp Lys Ala

1205 1210 1215

Cys Arg Leu Lys Ile His Leu Arg Ser His Thr Gly Glu Arg Pro

1220 1225 1230

Phe Ile Cys Asp Ser Asp Ser Cys Gly Trp Thr Phe Thr Ser Met

1235 1240 1245

Ser Lys Leu Leu Arg His Lys Arg Lys His Asp Asp Asp Arg Arg

1250 1255 1260

Phe Thr Cys Pro Val Glu Gly Cys Gly Lys Ser Phe Thr Arg Ala

1265 1270 1275

Glu His Leu Lys Gly His Ser Ile Thr His Leu Gly Thr Lys Pro

1280 1285 1290

Phe Glu Cys Pro Val Glu Gly Cys Cys Ala Arg Phe Ser Ala Arg

1295 1300 13G5

Ser Ser Leu Tyr Ile His Ser Lys Lys His Leu Gln Asp Val Gly

1310 1315 1320

Thr Pro Lys Ser Arg Cys Pro Val Ser Ser Cys Asn Arg Leu Phe

1325 1330 1335

Thr Ser Lys His Ser Met Lys Ala His Met Val Arg Gln His Ser

1340 1345 1350

Arg Arg Gln Asp Leu Val Pro Gln Leu Glu Ala Pro Ser Ser Leu

1355 1360 1365

Thr Pro Ser Ser Glu Leu Ser Ser Pro Gly Gln Ser Glu Leu Thr

1370 1375 1380

Asn Ile Asp Leu Ala Ala Leu Phe Ser Asp Thr Pro Ala Asn Ser

1385 1390 1395

Ser Ser Ser Thr Ala Gly Ser Asp Glu Ala Leu Asn Ser Gly Ile

1400 1405 1410

Leu Thr Ile Asp Val Thr Ser Val Ser Ser Ser Leu Gly Gly Asn

1415 1420 1425

Leu Pro Thr Asn Asn Asn Ser Leu Gly Pro Met Asp Pro Leu Val

1430 1435 1440

Leu Val Ala His Ser Asp Met Pro Pro Ser Leu Asp Ser Pro Leu

1445 1450 1455

Val Leu Gly Thr Pro Ala Thr Val Leu Gln Pro Gly Ser Phe Ser

1460 1465 1470

Ala Asp Asp Ser Gln Ala Met Ser Thr Gly Ala Val Gly Cys Leu

1475 1480 1485

Val Ala Leu Pro Met Arg Asn Leu Ser Gln Asp Ser Pro Ala Leu

1490 1495 1500

Thr Pro Ser Asn Asn Leu Thr Ala Leu Gly Thr Thr Pro Thr Ser

1505 1510 1515

Ser Asp Thr Thr Gln Glu Thr Ala Ser Val Pro Asp Leu Leu Val

1520 1525 1530

Pro Ile Lys Val Glu Gln Asp Leu Ser Pro Val Pro Asp Val Val

1535 1540 1545

Gln Gly Gln Lys Glu Ser His Gly Pro Ser Val Leu Ser Ser Ser

1550 1555 1560

Ala Glu Arg Leu Gly Ala Gln Lys Asp Ser Glu Leu Ser Ala Gly

1565 1570 1575

Thr Gly Ser Leu Tyr Leu Val

1580 1585

<210>7

<211>113

<212>PRT

<213>Rattus sp.

<400>7

Met Ala Ala Lys Thr Gly Ser Gln Leu Glu Arg Ser Ile Ser Thr Ile

1 5 10 15

Ile Asn Val Phe His Gln Tyr Ser Arg Lys Tyr Gly His Pro Asp Thr

20 25 30

Leu Asn Lys Ala Glu Phe Lys Glu Met Val Asn Lys Asp Leu Pro Asn

35 40 45

Phe Leu Lys Arg Glu Lys Arg Asn Glu Asn Leu Leu Arg Asp Ile Met

50 55 60

Glu Asp Leu Asp Thr Asn Gln Asp Asn Gln Leu Ser Phe Glu Glu Cys

65 70 75 80

Met Met Leu Met Gly Lys Leu Ile Phe Ala Cys His Glu Lys Leu His

85 90 95

Glu Asn Asn Pro Arg Gly His Asp His Arg His Gly Lys Gly Cys Gly

100 105 110

Lys

<210>8

<211>375

<212>PRT

<213>Rattus sp.

<400>8

Met Glu Glu Glu Ile Ala Ala Leu Val Ile Asp Asn Gly Ser Gly Met

1 5 10 15

Cys Lys Ala Gly Phe Ala Gly Asp Asp Ala Pro Arg Ala Val Phe Pro

20 25 30

Ser Ile Val Gly Arg Pro Arg His Gln Gly Val Met Val Gly Met Gly

35 40 45

Gln Lys Asp Ser Tyr Val Gly Asp Glu Ala Gln Ser Lys Arg Gly Ile

50 55 60

Leu Thr Leu Lys Tyr Pro Ile Glu His Gly Ile Val Thr Asn Trp Asp

65 70 75 80

Asp Met Glu Lys Ile Trp His His Thr Phe Tyr Asn Glu Leu Arg Val

85 90 95

Ala Pro Glu Glu His Pro Val Leu Leu Thr Glu Ala Pro Leu Asn Pro

100 105 110

Lys Ala Asn Arg Glu Lys Met Thr Gln Ile Met Phe Glu Thr Phe Asn

115 120 125

Thr Pro Ala Met Tyr Val Ala Ile Gln Ala Val Leu Ser Leu Tyr Ala

130 135 140

Ser Gly Arg Thr Thr Gly Ile Val Met Asp Ser Gly Asp Gly Val Thr

145 150 155 160

His Thr Val Pro Ile Tyr Glu Gly Tyr Ala Leu Pro His Ala Ile Leu

165 170 175

Arg Leu Asp Leu Ala Gly Arg Asp Leu Thr Asp Tyr Leu Met Lys Ile

180 185 190

Leu Thr Glu Arg Gly Tyr Ser Phe Thr Thr Thr Ala Glu Arg Glu Ile

195 200 205

Val Arg Asp Ile Lys Glu Lys Leu Cys Tyr Val Ala Leu Asp Phe Glu

210 215 220

Gln Glu Met Ala Thr Ala Ala Ser Ser Ser Ser Leu Glu Lys Ser Tyr

225 230 235 240

Glu Leu Pro Asp Gly Gln Val Ile Thr Ile Gly Asn Glu Arg Phe Arg

245 250 255

Cys Pro Glu Ala Leu Phe Gln Pro Ser Phe Leu Gly Met Glu Ser Cys

260 265 270

Gly Ile His Glu Thr Thr Phe Asn Ser Ile Met Lys Cys Asp Val Asp

275 280 285

Ile Arg Lys Asp Leu Tyr Ala Asn Thr Val Leu Ser Gly Gly Thr Thr

290 295 300

Met Tyr Pro Gly Ile Ala Asp Arg Met Gln Lys Glu Ile Thr Ala Leu

305 310 315 320

Ala Pro Ser Thr Met Lys Ile Lys Ile Ile Ala Pro Pro Glu Arg Lys

325 330 335

Tyr Ser Val Trp Ile Gly Gly Ser Ile Leu Ala Ser Leu Ser Thr Phe

340 345 350

Gln Gln Met Trp Ile Ser Lys Gln Glu Tyr Asp Glu Ser Gly Pro Ser

355 360 365

Ile Val His Arg Lys Cys Phe

370 375

<210>9

<211>501

<212>PRT

<213>Rattus sp.

<400>9

Met Ser Ser Pro Ala Gln Pro Ala Val Pro Ala Pro Leu Ala Asn Leu

1 5 10 15

Lys Ile Gln His Thr Lys Ile Phe Ile Asn Asn Glu Trp His Asp Ser

20 25 30

Val Ser Gly Lys Lys Phe Pro Val Leu Asn Pro Ala Thr Glu Glu Val

35 40 45

Ile Cys His Val Glu Glu Gly Asp Lys Ala Asp Val Asp Lys Ala Val

50 55 60

Lys Ala Ala Arg Gln Ala Phe Gln Ile Gly Ser Pro Trp Arg Thr Met

65 70 75 80

Asp Ala Ser Glu Arg Gly Arg Leu Leu Asn Lys Leu Ala Asp Leu Met

85 90 95

Glu Arg Asp Arg Leu Leu Leu Ala Thr Ile Glu Ala Ile Asn Gly Gly

100 105 110

Lys Val Phe Ala Asn Ala Tyr Leu Ser Asp Leu Gly Gly Ser Ile Lys

115 120 125

Ala Leu Lys Tyr Cys Ala Gly Trp Ala Asp Lys Ile His Gly Gln Thr

130 135 140

Ile Pro Ser Asp Gly Asp Ile Phe Thr Phe Thr Arg Arg Glu Pro Ile

145 150 155 160

Gly Val Cys Gly Gln Ile Ile Pro Trp Asn Phe Pro Leu Leu Met Phe

165 170 175

Ile Trp Lys Ile Gly Pro Ala Leu Ser Cys Gly Asn Thr Val Val Val

180 185 190

Lys Pro Ala Glu Gln Thr Pro Leu Thr Ala Leu His Met Ala Ser Leu

195 200 205

Ile Lys Glu Ala Gly Phe Pro Pro Gly Val Val Asn Ile Val Pro Gly

210 215 220

Tyr Gly Pro Thr Ala Gly Ala Ala Ile Ser Ser His Met Asp Val Asp

225 230 235 240

Lys Val Ala Phe Thr Gly Ser Thr Gln Val Gly Lys Leu Ile Lys Glu

245 250 255

Ala Ala Gly Lys Ser Asn Leu Lys Arg Val Thr Leu Glu Leu Gly Gly

260 265 270

Lys Ser Pro Cys Ile Val Phe Ala Asp Ala Asp Leu Asp Ile Ala Val

275 280 285

Glu Phe Ala His His Gly Val Phe Tyr His Gln Gly Gln Cys Cys Val

290 295 300

Ala Ala Ser Arg Ile Phe Val Glu Glu Ser Val Tyr Asp Glu Phe Val

305 310 315 320

Arg Lys Ser Val Glu Arg Ala Lys Lys Tyr Val Leu Gly Asn Pro Leu

325 330 335

Thr Gln Gly Ile Asn Gln Gly Pro Gln Ile Asp Lys Glu Gln His Asp

340 345 350

Lys Ile Leu Asp Leu Ile Glu Ser Gly Lys Lys Glu Gly Ala Lys Leu

355 360 365

Glu Cys Gly Gly Gly Arg Trp Gly Asn Lys Gly Phe Phe Val Gln Pro

370 375 380

Thr Val Phe Ser Asn Val Thr Asp Glu Met Arg Ile Ala Lys Glu Glu

385 390 395 400

Ile Phe Gly Pro Val Gln Gln Ile Met Lys Phe Lys Ser Ile Asp Asp

405 410 415

Val Ile Lys Arg Ala Asn Asn Thr Thr Tyr Gly Leu Ala Ala Gly Val

420 425 430

Phe Thr Lys Asp Leu Asp Arg Ala Ile Thr Val Ser Ser Ala Leu Gln

435 440 445

Ala Gly Val Val Trp Val Asn Cys Tyr Met Ile Leu Ser Ala Gln Cys

450 455 460

Pro Phe Gly Gly Phe Lys Met Ser Gly Asn Gly Arg Glu Leu Gly Glu

465 470 475 480

His Gly Leu Tyr Glu Tyr Thr Glu Leu Lys Thr Val Ala Met Lys Ile

485 490 495

Ser Gln Lys Asn Ser

500

<210>10

<211>204

<212>PRT

<213>Rattus sp.

<400>10

Met Ala Glu Gln Glu Pro Thr Ala Glu Gln Leu Ala Gln Ile Ala Ala

1 5 10 15

Glu Asn Glu Glu Asp Glu His Ser Val Asn Tyr Lys Pro Pro Ala Gln

20 25 30

Lys Ser Ile Gln Glu Ile Gln Glu Leu Asp Lys Asp Asp Glu Ser Leu

35 40 45

Arg Lys Tyr Lys Glu Ala Leu Leu Gly Arg Val Ala Val Ser Ala Asp

50 55 60

Pro Asn Val Pro Asn Val Ile Val Thr Arg Leu Thr Leu Val Cys Ser

65 70 75 80

Thr Ala Pro Gly Pro Leu Glu Leu Asp Leu Thr Gly Asp Leu Glu Ser

85 90 95

Phe Lys Lys Gln Ser Phe Val Leu Lys Glu Gly Val Glu Tyr Arg Ile

100 105 110

Lys Ile Ser Phe Arg Val Asn Arg Glu Ile Val Ser Gly Met Lys Tyr

115 120 125

Ile Gln His Thr Tyr Arg Lys Gly Val Lys Ile Asp Lys Thr Asp Tyr

130 135 140

Met Val Gly Ser Tyr Gly Pro Arg Ala Glu Glu Tyr Glu Phe Leu Thr

145 150 155 160

Pro Met Glu Glu Ala Pro Lys Gly Met Leu Ala Arg Gly Ser Tyr Asn

165 170 175

Ile Lys Ser Arg Phe Thr Asp Asp Asp Lys Thr Asp His Leu Ser Trp

180 185 190

Glu Trp Asn Leu Thr Ile Lys Lys Glu Trp Lys Asp

195 200

<210>11

<211>261

<212>PRT

<213>Rattus sp.

<400>11

Met Ala Ser Ala Asp Trp Gly Tyr Asp Ser Lys Asn Gly Pro Asp Gln

1 5 10 15

Trp Ser Lys Leu Tyr Pro Ile Ala Asn Gly Asn Asn Gln Ser Pro Ile

20 25 30

Asp Ile Lys Thr Ser Glu Ala Lys His Asp Ser Ser Leu Lys Pro Val

35 40 45

Ser Val Ser Tyr Asn Pro Ala Thr Ala Lys Glu Ile Val Asn Val Gly

50 55 60

His Ser Phe His Val Val Phe Asp Asp Ser Ser Asn Gln Ser Val Leu

65 70 75 80

Lys Gly Gly Pro Leu Ala Asp Ser Tyr Arg Leu Thr Gln Phe His Phe

85 90 95

His Trp Gly Asn Ser Asn Asp His Gly Ser Glu His Thr Val Asp Gly

100 105 110

Ala Lys Tyr Ser Gly Glu Leu His Leu Val His Trp Asn Ser Ala Lys

115 120 125

Tyr Ser Ser Ala Ala Glu Ala Ile Ser Lys Ala Asp Gly Leu Ala Ile

130 135 140

Ile Gly Val Leu Met Lys Val Gly Pro Ala Asn Pro Asn Leu Gln Lys

145 150 155 160

Val Leu Asp Ala Leu Ser Ser Val Lys Thr Lys Gly Lys Arg Ala Pro

165 170 175

Phe Thr Asn Phe Asp Pro Ser Ser Leu Leu Pro Ser Ser Leu Asp Tyr

180 185 190

Trp Thr Tyr Phe Gly Ser Leu Thr His Pro Pro Leu His Glu Ser Val

195 200 205

Thr Trp Val Ile Cys Lys Glu Ser Ile Ser Leu Ser Pro Glu Gln Leu

210 215 220

Ala Gln Leu Arg Gly Leu Leu Ser Ser Ala Glu Gly Glu Pro Ala Val

225 230 235 240

Pro Val Leu Ser Asn His Arg Pro Pro Gln Pro Leu Lys Gly Arg Thr

245 250 255

Val Arg Ala Ser Phe

260

<210>12

<211>260

<212>PRT

<213>Rattus sp.

<400>12

Met Ser His His Trp Gly Tyr Ser Lys Ser Asn Gly Pro Glu Asn Trp

1 5 10 15

His Lys Glu Phe Pro Ile Ala Asn Gly Asp Arg Gln Ser Pro Val Asp

20 25 30

Ile Asp Thr Gly Thr Ala Gln His Asp Pro Ser Leu Gln Pro Leu Leu

35 40 45

Ile Cys Tyr Asp Lys Val Ala Ser Lys Ser Ile Val Asn Asn Gly His

50 55 60

Ser Phe Asn Val Glu Phe Asp Asp Ser Gln Asp Phe Ala Val Leu Lys

65 70 75 80

Glu Gly Pro Leu Ser Gly Ser Tyr Arg Leu Ile Gln Phe His Phe His

85 90 95

Trp Gly Ser Ser Asp Gly Gln Gly Ser Glu His Thr Val Asn Lys Lys

100 105 110

Lys Tyr Ala Ala Glu Leu His Leu Val His Trp Asn Thr Lys Tyr Gly

115 120 125

Asp Phe Gly Lys Ala Val Gln His Pro Asp Gly Leu Ala Val Leu Gly

130 135 140

Ile Phe Leu Lys Ile Gly Pro Ala Ser Gln Gly Leu Gln Lys Ile Thr

145 150 155 160

Glu Ala Leu His Ser Ile Lys Thr Lys Gly Lys Arg Ala Ala Phe Ala

165 170 175

Asn Phe Asp Pro Cys Ser Leu Leu Pro Gly Asn Leu Asp Tyr Trp Thr

180 185 190

Tyr Pro Gly Ser Leu Thr Thr Pro Pro Leu Leu Glu Cys Val Thr Trp

195 200 205

Ile Val Leu Lys Glu Pro Ile Thr Val Ser Ser Glu Gln Met Ser His

210 215 220

Phe Arg Lys Leu Asn Phe Asn Ser Glu Gly Glu Ala Glu Glu Leu Met

225 230 235 240

Val Asp Asn Trp Arg Pro Ala Gln Pro Leu Lys Asn Arg Lys Ile Lys

245 250 255

Ala Ser Phe Lys

260

<210>13

<211>490

<212>PRT

<213>Rattus sp.

<400>13

Met Asp Pro Val Val Val Leu Leu Leu Ser Leu Phe Phe Leu Leu Phe

1 5 10 15

Leu Ser Leu Trp Arg Leu Ser Ser Gly Arg Gly Lys Leu Pro Pro Gly

20 25 30

Pro Thr Pro Leu Pro Ile Ile Gly Asn Phe Phe Gln Val Asp Met Lys

35 40 45

Asp Ile Arg Gln Ser Leu Thr Asn Phe Ser Lys Thr Tyr Gly Pro Val

50 55 60

Tyr Thr Leu Tyr Val Gly Ser Gln Pro Thr Val Val Leu His Gly Tyr

65 70 75 80

Glu Ala Leu Lys Glu Ala Leu Val Asp His Gly Glu Glu Phe Ser Gly

85 90 95

Arg Gly Arg Leu Pro Ile Cys Glu Lys Val Ala Lys Gly Gln Gly Ile

100 105 110

Ala Phe Ser His Gly Asn Val Trp Lys Ala Thr Arg His Phe Thr Val

115 120 125

Lys Thr Leu Arg Asn Leu Gly Met Gly Lys Gly Thr Ile Glu Asp Lys

130 135 140

Val Gln Glu Glu Ala Lys Trp Leu Val Lys Glu Leu Lys Lys Thr Asn

145 150 155 160

Gly Ser Pro Cys Asp Pro Gln Phe Ile Met Gly Cys Ala Pro Gly Asn

165 170 175

Val Ile Cys Cys Ile Ile Leu Gln Asn Arg Phe Asp Tyr Glu Asp Lys

180 185 190

Asp Phe Leu Asn Leu Ile Glu Lys Val Asn Glu Ala Val Lys Ile Ile

195 200 205

Ser Ser Pro Gly Ile Gln Val Phe Asn Ile Phe Pro Ile Leu Leu Asp

210 215 220

Tyr Cys Pro Gly Asn His Asn Ile Tyr Leu Lys Asn Tyr Thr Trp Val

225 230 235 240

Lys Ser Tyr Leu Leu Glu Lys Ile Lys Glu His Glu Glu Ser Leu Asp

245 250 255

Val Ser Asn Pro Arg Asp Phe Ile Asp Tyr Phe Leu Ile Glu Arg Asn

260 265 270

Gln Glu Asn Ala Asn Gln Trp Met Asn Tyr Thr Leu Glu His Leu Ala

275 280 285

Ile Met Val Thr Asp Leu Phe Phe Ala Gly Ile Glu Thr Val Ser Ser

290 295 300

Thr Met Arg Phe Ala Leu Leu Leu Leu Met Lys Tyr Pro His Val Thr

305 310 315 320

Ala Lys Val Gln Glu Glu Ile Asp His Val Ile Gly Arg His Arg Ser

325 330 335

Pro Ser Met Gln Asp Arg Ser His Met Pro Tyr Thr Asn Ala Met Val

340 345 350

His Glu Val Gln Arg Tyr Ile Asp Ile Gly Pro Asn Gly Leu Leu His

355 360 365

Asp Val Thr Cys Asp Thr Lys Phe Arg Asn Tyr Phe Ile Pro Lys Gly

370 375 380

Thr Ala Val Leu Thr Ser Leu Thr Ser Val Leu His Asp Ser Lys Glu

385 390 395 400

Phe Pro Asn Pro Glu Met Phe Asp Pro Gly His Phe Leu Asp Glu Asn

405 410 415

Gly Asn Phe Lys Lys Ser Asp Tyr Phe Ile Pro Phe Ser Ala Gly Lys

420 425 430

Arg Met Cys Leu Gly Glu Ser Leu Ala Arg Met Glu Leu Phe Leu Phe

435 440 445

Leu Thr Thr Ile Leu Gln Asn Phe Lys Leu Lys Ser Leu Val Asp Pro

450 455 460

Lys Asp Ile Asn Thr Thr Pro Ile Cys Ser Ser Leu Ser Ser Val Pro

465 470 475 480

Pro Thr Phe Gln Met Arg Phe Ile Pro Leu

485 490

<210>14

<211>609

<212>PRT

<213>Rattus sp.

<400>14

Met Ser Glu Trp Glu Ser Tyr Tyr Lys Thr Glu Gly Glu Glu Glu Glu

1 5 10 15

Glu Glu Glu Gln Ser Pro Asp Thr Asn Gly Glu Tyr Lys Tyr Ser Gly

20 25 30

Arg Asp Ser Leu Ile Phe Leu Val Asp Ala Ser Arg Ala Met Phe Glu

35 40 45

Ser Gln Gly Glu Asp Glu Leu Thr Pro Phe Asp Met Ser Ile Gln Cys

50 55 60

Ile Gln Ser Val Tyr Thr Ser Lys Ile Ile Ser Ser Asp Arg Asp Leu

65 70 75 80

Leu Ala Val Val Phe Tyr Gly Thr Glu Lys Asp Lys Asn Ser Val Asn

85 90 95

Phe Lys Ser Ile Tyr Val Leu Gln Asp Leu Asp Asn Pro Gly Ala Lys

100 105 110

Arg Val Leu Glu Leu Asp Arg Phe Lys Gly Gln Gln Gly Lys Lys His

115 120 125

Phe Arg Asp Thr Ile Gly His Gly Ser Asp Tyr Ser Leu Ser Glu Val

130 135 140

Leu Trp Val Cys Ala Asn Leu Phe Ser Asp Val Gln Phe Lys Met Ser

145 150 155 160

His Lys Arg Ile Met Leu Phe Thr Asn Glu Asp Asp Pro His Gly Asn

165 170 175

Asp Ser Ala Lys Ala Ser Arg Ala Arg Thr Lys Ala Ser Asp Leu Arg

180 185 190

Asp Thr Gly Ile Phe Leu Asp Leu Met His Leu Lys Lys Arg Gly Gly

195 200 205

Phe Asp Val Ser Leu Phe Tyr Arg Asp Ile Ile Ser Ile Ala Glu Asp

210 215 220

Glu Asp Leu Gly Val His Phe Glu Glu Ser Ser Lys Leu Glu Asp Leu

225 230 235 240

Leu Arg Lys Val Arg Ala Lys Glu Thr Lys Lys Arg Val Leu Ser Arg

245 250 255

Leu Lys Phe Lys Leu Gly Lys Asp Val Ala Leu Met Val Gly Val Tyr

260 265 270

Asn Leu Val Gln Lys Ala Asn Lys Pro Phe Pro Val Arg Leu Tyr Arg

275 280 285

Glu Thr Asn Glu Pro Val Lys Thr Lys Thr Arg Thr Phe Asn Val Asn

290 295 300

Thr Gly Ser Leu Leu Leu Pro Ser Asp Thr Lys Arg Ser Leu Thr Phe

305 310 315 320

Gly Thr Arg Gln Ile Val Leu Glu Lys Glu Glu Thr Glu Glu Leu Lys

325 330 335

Arg Phe Asp Glu Pro Gly Leu Ile Leu Met Gly Phe Lys Pro Met Val

340 345 350

Met Leu Lys Asn His His Tyr Leu Arg Pro Ser Leu Phe Leu Tyr Pro

355 360 365

Glu Glu Ser Leu Val Asn Gly Ser Ser Thr Leu Phe Ser Ala Leu Leu

370 375 380

Thr Lys Cys Val Glu Lys Glu Val Ile Ala Val Cys Arg Tyr Thr Ala

385 390 395 400

Arg Lys Asn Val Ser Pro Tyr Phe Val Ala Leu Val Pro Gln Glu Glu

405 410 415

Glu Leu Asp Asp Gln Asn Ile Gln Val Thr Pro Ala Gly Phe Gln Leu

420 425 430

Val Phe Leu Pro Tyr Ala Asp Asp Lys Arg Lys Val Pro Phe Thr Glu

435 440 445

Lys Val Met Ala Asn Pro Glu Gln Ile Asp Lys Met Lys Ala His Val

450 455 460

Gln Lys Leu Arg Phe Thr Tyr Arg Ser Asp Ser Phe Glu Asn Pro Val

465 470 475 480

Leu Gln Gln His Phe Arg Asn Leu Glu Ala Leu Ala Leu Asp Met Met

485 490 495

Glu Ser Glu Gln Val Val Asp Leu Thr Leu Pro Lys Val Glu Ala Ile

500 505 510

Lys Lys Arg Leu Gly Ser Leu Ala Asp Glu Phe Lys Glu Leu Val Tyr

515 520 525

Pro Pro Gly Tyr Asn Pro Glu Gly Lys Ile Ala Lys Arg Lys Ala Asp

530 535 540

Asn Glu Gly Ser Ala Ser Lys Lys Pro Lys Val Glu Leu Ser Glu Glu

545 550 555 560

Glu Leu Lys Asp Leu Phe Ala Lys Gly Thr Leu Gly Lys Leu Thr Val

565 570 575

Pro Ala Leu Arg Asp Ile Cys Lys Ala Tyr Gly Leu Lys Ser Gly Pro

580 585 590

Lys Lys Gln Glu Leu Leu Glu Ala Leu Ser Arg Hi s Leu Glu Lys Thr

595 600 605

Asp

<210>15

<211>1961

<212>PRT

<213>Rattus sp.

<400>15

Met Ala Gln Gln Ala Ala Asp Lys Tyr Leu Tyr Val Asp Lys Asn Phe

1 5 10 15

Ile Asn Asn Pro Leu Ala Gln Ala Asp Cys Gly Ala Lys Lys Leu Val

20 25 30

Trp Val Pro Ser Thr Lys Asn Gly Phe Glu Pro Ala Ser Leu Lys Glu

35 40 45

Glu Val Gly Glu Glu Ala Ile Val Glu Leu Val Glu Asn Gly Lys Lys

50 55 60

Val Lys Val Asn Lys Asp Asp Ile Gln Lys Met Asn Pro Pro Lys Phe

65 70 75 80

Ser Lys Val Glu Asp Met Ala Glu Leu Thr Cys Leu Asn Glu Ala Ser

85 90 95

Val Leu His Asn Leu Lys Glu Arg Tyr Tyr Ser Gly Leu Ile Tyr Thr

100 105 110

Tyr Ser Gly Leu Phe Cys Val Val Ile Asn Pro Tyr Lys Asn Leu Pro

115 120 125

Ile Tyr Ser Glu Glu Ile Val Asp Met Tyr Lys Gly Lys Lys Arg His

130 135 140

Glu Met Pro Pro His Ile Tyr Ala Ile Thr Asp Thr Ala Tyr Arg Ser

145 150 155 160

Met Met Gln Asp Arg Glu Asp Gln Ser Ile Leu Cys Thr Gly Glu Ser

165 170 175

Gly Ala Gly Lys Thr Glu Asn Thr Lys Lys Val Ile Gln Tyr Leu Ala

180 185 190

His Val Ala Ser Ser His Lys Ser Lys Lys Asp Gln Gly Glu Leu Glu

195 200 205

Arg Gln Leu Leu Gln Ala Asn Pro Ile Leu Glu Ala Phe Gly Asn Ala

210 215 220

Lys Thr Val Lys Asn Asp Asn Ser Ser Arg Phe Gly Lys Phe Ile Arg

225 230 235 240

Ile Asn Phe Asp Val Asn Gly Tyr Ile Val Gly Ala Asn Ile Glu Thr

245 250 255

Tyr Leu Leu Glu Lys Ser Arg Ala Ile Arg Gln Ala Lys Glu Glu Arg

260 265 270

Thr Phe His Ile Phe Tyr Tyr Leu Leu Ser Gly Ala Gly Glu His Leu

275 280 285

Lys Thr Asp Leu Leu Leu Glu Pro Tyr Asn Lys Tyr Arg Phe Leu Ser

290 295 300

Asn Gly His Val Thr Ile Pro Gly Gln Gln Asp Lys Asp Met Phe Gln

305 310 315 320

Glu Thr Met Glu Ala Met Arg Ile Met Gly Ile Pro Glu Asp Glu Gln

325 330 335

Met Gly Leu Leu Arg Val Ile Ser Gly Val Leu Gln Leu Gly Asn Ile

340 345 350

Val Phe Lys Lys Glu Arg Asn Thr Asp Gln Ala Ser Met Pro Asp Asn

355 360 365

Thr Ala Ala Gln Lys Val Ser His Leu Leu Gly Ile Asn Val Thr Asp

370 375 380

Phe Thr Arg Gly Ile Leu Thr Pro Arg Ile Lys Val Gly Arg Asp Tyr

385 390 395 400

Val Gln Lys Ala Gln Thr Lys Glu Gln Ala Asp Phe Ala Ile Glu Ala

405 410 415

Leu Ala Lys Ala Thr Tyr Glu Arg Met Phe Arg Trp Leu Val Leu Arg

420 425 430

Ile Asn Lys Ala Leu Asp Lys Thr Lys Arg Gln Gly Ala Ser Phe Ile

435 440 445

Gly Ile Leu Asp Ile Ala Gly Phe Glu Ile Phe Asp Leu Asn Ser Phe

450 455 460

Glu Gln Leu Cys Ile Asn Tyr Thr Asn Glu Lys Leu Gln Gln Leu Phe

465 470 475 480

Asn His Thr Met Phe Ile Leu Glu Gln Glu Glu Tyr Gln Arg Glu Gly

485 490 495

Ile Glu Trp Asn Phe Ile Asp Phe Gly Leu Asp Leu Gln Pro Cys Ile

500 505 510

Asp Leu Ile Glu Lys Pro Ala Gly Pro Pro Gly Ile Leu Ala Leu Leu

515 520 525

Asp Glu Glu Cys Trp Phe Pro Lys Ala Thr Asp Lys Ser Phe Val Glu

530 535 540

Lys Val Val Gln Glu Gln Gly Thr His Pro Lys Phe Gln Lys Pro Lys

545 550 555 560

Gln Leu Lys Asp Lys Ala Asp Phe Cys Ile Ile His Tyr Ala Gly Lys

565 570 575

Val Asp Tyr Lys Ala Asp Glu Trp Leu Met Lys Asn Met Asp Pro Leu

580 585 590

Asn Asp Asn Ile Ala Thr Leu Leu His Gln Ser Ser Asp Lys Phe Val

595 600 605

Ser Glu Leu Trp Lys Asp Val Asp Arg Ile Ile Gly Leu Asp Gln Val

610 615 620

Ala Gly Met Ser Glu Thr Ala Leu Pro Gly Ala Phe Lys Thr Arg Lys

625 630 635 640

Gly Met Phe Arg Thr Val Gly Gln Leu Tyr Lys Glu Gln Leu Ala Lys

645 650 655

Leu Met Ala Thr Leu Arg Asn Thr Asn Pro Asn Phe Val Cys Cys Ile

660 665 670

Ile Pro Asn His Glu Lys Lys Ala Gly Lys Leu Asp Pro His Leu Val

675 680 685

Leu Asp Gln Leu Arg Cys Asn Gly Val Leu Glu Gly Ile Arg Ile Cys

690 695 700

Arg Gln Gly Phe Pro Asn Arg Val Val Phe Gln Glu Phe Arg Gln Arg

705 710 715 720

Tyr Glu Ile Leu Thr Pro Asn Ser Ile Pro Lys Gly Phe Met Asp Gly

725 730 735

Lys Gln Ala Cys Val Leu Met Ile Lys Ala Leu Glu Leu Asp Ser Asn

740 745 750

Leu Tyr Arg Ile Gly Gln Ser Lys Val Phe Phe Arg Ser Gly Val Leu

755 760 765

Ala His Leu Glu Glu Glu Arg Asp Leu Lys Ile Thr Asp Val Ile Ile

770 775 780

Gly Phe Gln Ala Cys Cys Arg Gly Tyr Leu Ala Arg Lys Ala Phe Ala

785 790 795 800

Lys Arg Gln Gln Gln Leu Thr Ala Met Lys Val Leu Gln Arg Asn Cys

805 810 815

Ala Ala Tyr Leu Arg Leu Arg Asn Trp Gln Trp Trp Arg Leu Phe Thr

820 825 830

Lys Val Lys Pro Leu Leu Asn Ser Ile Arg His Glu Asp Glu Leu Leu

835 840 845

Ala Lys Glu Ala Glu Leu Thr Lys Val Arg Glu Lys His Leu Ala Ala

850 855 860

Glu Asn Arg Leu Thr Glu Met Glu Thr Met Gln Ser Gln Leu Met Ala

865 870 875 880

Glu Lys Leu Gln Leu Gln Glu Gln Leu Gln Ala Lys Thr Glu Leu Cys

885 890 895

Ala Glu Ala Glu Glu Leu Arg Ala Arg Leu Thr Ala Lys Lys Gln Glu

900 905 910

Leu Glu Glu Ile Cys His Asp Leu Glu Ala Arg Val Glu Glu Glu Glu

915 920 925

Glu Arg Cys Gln Tyr Leu Gln Ala Glu Lys Lys Lys Met Gln Gln Asn

930 935 940

Ile Gln Glu Leu Glu Glu Gln Leu Glu Glu Glu Glu Ser Ala Arg Gln

945 950 955 960

Lys Leu Gln Leu Glu Lys Val Thr Thr Glu Ala Lys Leu Lys Lys Leu

965 970 975

Glu Glu Asp Gln Ile Ile Met Glu Asp Gln Asn Cys Lys Leu Ala Lys

980 985 990

Glu Lys Lys Leu Leu Glu Asp Arg Val Ala Glu Phe Thr Thr Asp Leu

995 1000 1005

Met Glu Glu Glu Glu Lys Ser Lys Ser Leu Ala Lys Leu Lys Asn

1010 1015 1020

Lys His Glu Ala Met Ile Thr Asp Leu Glu Glu Arg Leu Arg Arg

1025 1030 1035

Glu Glu Lys Gln Arg Gln Glu Leu Glu Lys Thr Arg Arg Lys Leu

1040 1045 1050

Glu Gly Asp Ser Thr Asp Leu Ser Asp Gln Ile Ala Glu Leu Gln

1055 1060 1065

Ala Gln Ile Ala Glu Leu Lys Met Gln Leu Ala Lys Lys Glu Glu

1070 1075 1080

Glu Leu Gln Ala Ala Leu Ala Arg Val Glu Glu Glu Ala Ala Gln

1085 1090 1095

Lys Asn Met Ala Leu Lys Lys Ile Arg Glu Leu Glu Thr Gln Ile

1100 1105 1110

Ser Glu Leu Gln Glu Asp Leu Glu Ser Glu Arg Ala Cys Arg Asn

1115 1120 1125

Lys Ala Glu Lys Gln Lys Arg Asp Leu Gly Glu Glu Leu Glu Ala

1130 1135 1140

Leu Lys Thr Glu Leu Glu Asp Thr Leu Asp Ser Thr Ala Ala Gln

1145 1150 1155

Gln Glu Leu Arg Ser Lys Arg Glu Gln Glu Val Ser Ile Leu Lys

1160 1165 1170

Lys Thr Leu Glu Asp Glu Ala Lys Thr His Glu Ala Gln Ile Gln

1175 1180 1185

Glu Met Arg Gln Lys His Ser Gln Ala Val Glu Glu Leu Ala Glu

1190 1195 1200

Gln Leu Glu Gln Thr Lys Arg Val Lys Ala Thr Leu Glu Lys Ala

1205 1210 1215

Lys Gln Thr Leu Glu Asn Glu Arg Gly Glu Leu Ala Asn Glu Val

1220 1225 1230

Lys Ala Leu Leu Gln Gly Lys Gly Asp Ser Glu His Lys Arg Lys

1235 1240 1245

Lys Val Glu Ala Gln Leu Gln Glu Leu Gln Val Lys Phe Ser Glu

1250 1255 1260

Gly Glu Arg Val Arg Thr Glu Leu Ala Asp Lys Val Ser Lys Leu

1265 1270 1275

Gln Val Glu Leu Asp Ser Val Thr Gly Leu Leu Asn Gln Ser Asp

1280 1285 1290

Ser Lys Ser Ser Lys Leu Thr Lys Asp Phe Ser Ala Leu Glu Ser

1295 1300 1305

Gln Leu Gln Asp Thr Gln Glu Leu Leu Gln Glu Glu Asn Arg Gln

1310 1315 1320

Lys Leu Ser Leu Ser Thr Lys Leu Lys Gln Met Glu Asp Glu Lys

1325 1330 1335

Asn Ser Phe Arg Glu Gln Leu Glu Glu Glu Glu Glu Glu Ala Lys

1340 1345 1350

Arg Asn Leu Glu Lys Gln Ile Ala Thr Leu His Ala Gln Val Thr

1355 1360 1365

Asp Met Lys Lys Lys Met Glu Asp Gly Val Gly Cys Leu Glu Thr

1370 1375 1380

Ala Glu Glu Ala Lys Arg Arg Leu Gln Lys Asp Leu Glu Gly Leu

1385 1390 1395

Ser Gln Arg Leu Glu Glu Lys Val Ala Ala Tyr Asp Lys Leu Glu

1400 1405 1410

Lys Thr Lys Thr Arg Leu Gln Gln Glu Leu Asp Asp Leu Leu Val

1415 1420 1425

Asp Leu Asp His Gln Arg Gln Ser Val Ser Asn Leu Glu Lys Lys

1430 1435 1440

Gln Lys Lys Phe Asp Gln Leu Leu Ala Glu Glu Lys Thr Ile Ser

1445 1450 1455

Ala Lys Tyr Ala Glu Glu Arg Asp Arg Ala Glu Ala Glu Ala Arg

1460 1465 1470

Glu Lys Glu Thr Lys Ala Leu Ser Leu Ala Arg Ala Leu Glu Glu

1475 1480 1485

Ala Met Glu Gln Lys Ala Glu Leu Glu Arg Leu Asn Lys Gln Phe

1490 1495 1500

Arg Thr Glu Met Glu Asp Leu Met Ser Ser Lys Asp Asp Val Gly

1505 1510 1515

Lys Ser Val His Glu Leu Glu Lys Ser Asn Arg Ala Leu Glu Gln

1520 1525 1530

Gln Val Glu Glu Met Lys Thr Gln Leu Glu Glu Leu Glu Asp Glu

1535 1540 1545

Leu Gln Ala Thr Glu Asp Ala Lys Leu Arg Leu Glu Val Asn Leu

1550 1555 1560

Gln Ala Met Lys Ala Gln Phe Glu Arg Asp Leu Gln Gly Arg Asp

1565 1570 1575

Glu Gln Ser Glu Glu Lys Lys Lys Gln Leu Val Arg Gln Val Arg

1580 1585 1590

Glu Met Glu Ala Glu Leu Glu Asp Glu Arg Lys Gln Arg Ser Ile

1595 1600 1605

Ala Met Ala Ala Arg Lys Lys Leu Glu Met Asp Leu Lys Asp Leu

1610 1615 1620

Glu Ala His Ile Asp Thr Ala Asn Lys Asn Arg Glu Glu Ala Ile

1625 1630 1635

Lys Gln Leu Arg Lys Leu Gln Ala Gln Met Lys Asp Cys Met Arg

1640 1645 1650

Asp Val Asp Asp Thr Arg Ala Ser Arg Glu Glu Ile Leu Ala Gln

1655 1660 1665

Ala Lys Glu Asn Glu Lys Lys Leu Lys Ser Met Glu Ala Glu Met

1670 1675 1680

Ile Gln Leu Gln Glu Glu Leu Ala Ala Ala Glu Arg Ala Lys Arg

1685 1690 1695

Gln Ala Gln Gln Glu Arg Asp Glu Leu Ala Asp Glu Ile Ala Asn

1700 1705 1710

Ser Ser Gly Lys Gly Ala Leu Ala Leu Glu Glu Lys Arg Arg Leu

1715 1720 1725

Glu Ala Leu Ile Ala Leu Leu Glu Glu Glu Leu Glu Glu Glu Gln

1730 1735 1740

Gly Asn Thr Glu Leu Ile Asn Asp Arg Leu Lys Lys Ala Asn Leu

1745 1750 1755

Gln Ile Asp Gln Ile Asn Thr Asp Leu Asn Leu Glu Arg Ser His

1760 1765 1770

Ala Gln Lys Asn Glu Asn Ala Arg Gln Gln Leu Glu Arg Gln Asn

1775 1780 1785

Lys Glu Leu Lys Ala Lys Leu Gln Glu Met Glu Ser Ala Val Lys

1790 1795 1800

Ser Lys Tyr Lys Ala Ser Ile Ala Ala Leu Glu Ala Lys Ile Ala

1805 1810 1815

Gln Leu Glu Glu Gln Leu Asp Asn Glu Thr Lys Glu Arg Gln Ala

1820 1825 1830

Ala Ser Lys Gln Val Arg Arg Ala Glu Lys Lys Leu Lys Asp Val

1835 1840 1845

Leu Leu Gln Val Glu Asp Glu Arg Arg Asn Ala Glu Gln Phe Lys

1850 1855 1860

Asp Gln Ala Asp Lys Ala Ser Thr Arg Leu Lys Gln Leu Lys Arg

1865 1870 1875

Gln Leu Glu Glu Ala Glu Glu Glu Ala Gln Arg Ala Asn Ala Ser

1880 1885 1890

Arg Arg Lys Leu Gln Arg Glu Leu Glu Asp Ala Thr Glu Thr Ala

1895 1900 1905

Asp Ala Met Asn Arg Glu Val Ser Ser Leu Lys Asn Lys Leu Arg

1910 1915 1920

Arg Gly Asp Met Pro Phe Val Val Thr Arg Arg Ile Val Arg Lys

1925 1930 1935

Gly Thr Gly Asp Cys Ser Asp Glu Glu Val Asp Gly Lys Ala Asp

1940 1945 1950

Gly Ala Asp Ala Lys Ala Thr Glu

1955 1960

<210>16

<211>151

<212>PRT

<213>Rattus sp.

<400>16

Met Cys Asp Phe Thr Glu Asp Gln Thr Ala Glu Phe Lys Glu Ala Phe

1 5 10 15

Gln Leu Phe Asp Arg Thr Gly Asp Gly Lys Ile Leu Tyr Ser Gln Cys

20 25 30

Gly Asp Val Met Arg Ala Leu Gly Gln Asn Pro Thr Asn Ala Glu Val

35 40 45

Leu Lys Val Leu Gly Asn Pro Lys Ser Asp Glu Met Asn Val Lys Val

50 55 60

Leu Asp Phe Glu His Phe Leu Pro Met Leu Gln Thr Val Ala Lys Asn

65 70 75 80

Lys Asp Gln Gly Thr Tyr Glu Asp Tyr Val Glu Gly Leu Arg Val Phe

85 90 95

Asp Lys Glu Gly Asn Gly Thr Val Met Gly Ala Glu Ile Arg His Val

100 105 110

Leu Val Thr Leu Gly Glu Lys Met Thr Glu Glu Glu Val Glu Met Leu

115 120 125

Val Ala Gly His Glu Asp Ser Asn Gly Cys Ile Asn Tyr Glu Glu Leu

130 135 140

Leu Arg Met Val Leu Asn Gly

145 150

<210>17

<211>554

<212>PRT

<213>Rattus sp.

<400>17

Met Tyr Ala Leu Ala Leu Leu Ala Ser Leu Leu Val Thr Ala Leu Thr

1 5 10 15

Ser Pro Val Gln Asp Pro Lys Ile Cys Ser Gly Gly Ser Ala Val Val

20 25 30

Cys Arg Asp Val Lys Thr Ala Val Asp Cys Arg Ala Val Lys His Cys

35 40 45

Gln Gln Met Val Trp Ser Lys Pro Thr Ala Lys Ser Leu Pro Cys Asp

50 55 60

Ile Cys Lys Thr Val Val Thr Glu Ala Gly Asn Leu Leu Lys Asp Asn

65 70 75 80

Ala Thr Glu Glu Glu Ile Leu His Tyr Leu Glu Lys Thr Cys Ala Trp

85 90 95

Ile His Asp Ser Ser Leu Ser Ala Ser Cys Lys Glu Val Val Asp Ser

100 105 110

Tyr Leu Pro Val Ile Leu Asp Met Ile Lys Gly Glu Met Ser Asn Pro

115 120 125

Gly Glu Val Cys Ser Ala Leu Asn Leu Cys Gln Ser Leu Gln Glu Tyr

130 135 140

Leu Ala Glu Gln Asn Gln Arg Gln Leu Glu Ser Asn Lys Ile Pro Glu

145 150 155 160

Val Asp Leu Ala Arg Val Val Ala Pro Phe Met Ser Asn Ile Pro Leu

165 170 175

Leu Leu Tyr Pro Gln Asp Arg Pro Arg Ser Gln Pro Gln Pro Lys Ala

180 185 190

Asn Glu Asp Val Cys Gln Asp Cys Met Lys Leu Val Thr Asp Ile Gln

195 200 205

Thr Ala Val Arg Thr Asn Ser Ser Phe Val Gln Gly Leu Val Asp His

210 215 220

Val Lys Glu Asp Cys Asp Arg Leu Gly Pro Gly Val Ser Asp Ile Cys

225 230 235 240

Lys Asn Tyr Val Asp Gln Tyr Ser Glu Val Ala Val Gln Met Met Met

245 250 255

His Met Gln Pro Lys Glu Ile Cys Val Met Val Gly Phe Cys Asp Glu

260 265 270

Val Lys Arg Val Pro Met Arg Thr Leu Val Pro Ala Thr Glu Ala Ile

275 280 285

Lys Asn Ile Leu Pro Ala Leu Glu Leu Thr Asp Pro Tyr Glu Gln Asp

290 295 300

Val Ile Gln Ala Gln Asn Val Ile Phe Cys Gln Val Cys Gln Leu Val

305 310 315 320

Met Arg Lys Leu Ser Glu Leu Ile Ile Asn Asn Ala Thr Glu Glu Leu

325 330 335

Leu Ile Lys Gly Leu Ser Lys Ala Cys Ser Leu Leu Pro Ala Pro Ala

340 345 350

Ser Thr Lys Cys Gln Glu Val Leu Val Thr Phe Gly Pro Ser Leu Leu

355 360 365

Asp Val Leu Met His Glu Val Asn Pro Asn Phe Leu Cys Gly Val Ile

370 375 380

Ser Leu Cys Ser Ala Asn Pro Asn Leu Val Gly Thr Leu Glu Gln Pro

385 390 395 400

Ala Ala Ala Ile Val Ser Ala Leu Pro Lys Glu Pro Ala Pro Pro Lys

405 410 415

Gln Pro Glu Glu Pro Lys Gln Ser Ala Leu Arg Ala His Val Pro Pro

420 425 430

Gln Lys Asn Gly Gly Phe Cys Glu Val Cys Lys Lys Leu Val Ile Tyr

435 440 445

Leu Glu His Asn Leu Glu Lys Asn Ser Thr Lys Glu Glu Ile Leu Ala

450 455 460

Ala Leu Glu Lys Gly Cys Ser Phe Leu Pro Asp Pro Tyr Gln Lys Gln

465 470 475 480

Cys Asp Glu Phe Val Ala Glu Tyr Glu Pro Leu Leu Leu Glu Ile Leu

485 490 495

Val Glu Val Met Asp Pro Ser Phe Val Cys Ser Lys Ile Gly Val Cys

500 505 510

Pro Ser Ala Tyr Lys Leu Leu Leu Gly Thr Glu Lys Cys Val Trp Gly

515 520 525

Pro Gly Tyr Trp Cys Gln Asn Ser Glu Thr Ala Ala Arg Cys Asn Ala

530 535 540

Val Asp His Cys Lys Arg His Val Trp Asn

545 550

<210>18

<211>395

<212>PRT

<213>Rattus sp.

<400>18

Met Lys Pro Ala Gln Ser Ser Ile Arg Pro Cys Arg Leu Arg Pro Pro

1 5 10 15

Asn Trp Ala Glu Gly Lys Asp Phe Trp Val Ser Asp Pro Lys Lys Gly

20 25 30

Gln Ala Arg Asp Gly Thr Ala Leu Ala Val Ser Arg Ala Gly Ala Leu

35 40 45

Gln Pro Ser Gly Gly Ala Gly Leu Gly Ser Gly Ala Lys Ala Ser His

50 55 60

Val Arg Pro Ala Ala Leu Leu Ser Ser Ile Ser Leu Asn Gly Leu Arg

65 70 75 80

Arg Gly Ser Pro Pro Ile Ser Thr Leu Trp Asn Ala Gly Arg Gly Glu

85 90 95

Leu Gln Asp Arg Arg Asn His Leu Pro Lys Arg Gly Glu Glu Ala Glu

100 105 110

Ser Gln Phe Lys Arg Arg Arg Glu Lys Asp Glu Glu Ser Gly Trp Pro

115 120 125

Ile Glu Ala Ala Glu Asn Gly Arg Gln Ala Ser Phe Arg Phe Ala Ser

130 135 140

Gly Gly Arg Lys Trp Pro Phe Leu Gly Gly Trp Lys Val Arg Lys Phe

145 150 155 160

Val Arg Ala Ala Ala Lys Leu Arg Arg Asp Ala His Ser Trp Phe Ser

165 170 175

Arg Leu Ser Arg Val Ser Gly Ala Gly Arg Arg Ala Gly Val Ala Arg

180 185 190

Pro Gln Glu Val Ser Ser Pro Gly Gly Gly Glu Arg Gly Gly Arg Arg

195 200 205

Glu Pro Arg Leu Gly Ser Ala Pro Gly Gln Asp Leu Thr Ala Thr Met

210 215 220

Ser Ser Lys Arg Ala Lys Thr Lys Thr Thr Lys Lys Arg Pro Gln Arg

225 230 235 240

Ala Thr Ser Asn Val Phe Ala Met Phe Asp Gln Ser Gln Ile Gln Glu

245 250 255

Phe Lys Glu Ala Phe Asn Met Ile Asp Gln Asn Arg Asp Gly Phe Ile

260 265 270

Asp Lys Glu Asp Leu His Asp Met Leu Ala Ser Met Gly Lys Asn Pro

275 280 285

Thr Asp Glu Tyr Leu Asp Ala Met Met Asn Glu Ala Pro Gly Pro Ile

290 295 300

Asn Phe Thr Met Phe Leu Thr Met Phe Gly Glu Lys Leu Asn Gly Thr

305 310 315 320

Asp Pro Glu Asp Val Ile Arg Asn Ala Phe Ala Cys Phe Asp Glu Glu

325 330 335

Ala Ile Gly Thr Ile Gln Glu Asp Tyr Leu Arg Glu Leu Leu Thr Thr

340 345 350

Met Gly Asp Arg Phe Thr Asp Glu Glu Val Asp Glu Leu Tyr Arg Glu

355 360 365

Ala Pro Ile Asp Lys Lys Gly Asn Phe Asn Tyr Ile Glu Phe Thr Arg

370 375 380

Ile Leu Lys His Gly Ala Lys Asp Lys Asp Asp

385 390 395

<210>19

<211>928

<212>PRT

<213>Rattus sp.

<400>19

Met Gly Asp Met Gln Asp His Glu Lys Val Leu Glu Ile Pro Asp Arg

1 5 10 15

Asp Ser Glu Glu Glu Leu Glu His Val Ile Glu Gln Ile Ala Tyr Arg

20 25 30

Asp Leu Asp Ile Pro Val Thr Glu Met Gln Glu Ser Glu Ala Leu Pro

35 40 45

Thr Glu Gln Thr Ala Thr Asp Tyr Ile Pro Thr Ser Thr Ser Thr Ser

50 55 60

His Pro Ser Ser Ser Gln Val Tyr Val Glu Leu Gln Glu Leu Met Met

65 70 75 80

Asp Gln Arg Asn Gln Glu Leu Gln Trp Val Glu Ala Ala His Trp Ile

85 90 95

Gly Leu Glu Glu Asn Leu Arg Glu Asp Gly Val Trp Gly Arg Pro His

100 105 110

Leu Ser Tyr Leu Thr Phe Trp Ser Leu Leu Glu Leu Gln Lys Val Phe

115 120 125

Ser Lys Gly Thr Phe Leu Leu Asp Leu Ala Glu Thr Ser Leu Ala Gly

130 135 140

Val Ala Asn Lys Leu Leu Asp Ser Phe Ile Tyr Glu Asp Gln Ile Arg

145 150 155 160

Pro Gln Asp Arg Asp Glu Leu Leu Arg Ala Leu Leu Leu Lys Arg Ser

165 170 175

His Ala Glu Asp Leu Lys Asp Leu Glu Gly Val Lys Pro Ala Val Leu

180 185 190

Thr Arg Ser Gly Ala Pro Ser Glu Pro Leu Leu Pro His Gln Pro Ser

195 200 205

Leu Glu Thr Lys Leu Tyr Cys Ala Gln Ala Glu Gly Gly Ser Glu Glu

210 215 220

Pro Ser Pro Ser Gly Ile Leu Lys Ile Pro Pro Asn Ser Glu Thr Thr

225 230 235 240

Leu Val Leu Val Gly Arg Ala Ser Phe Leu Val Lys Pro Val Leu Gly

245 250 255

Phe Val Arg Leu Lys Glu Ala Val Pro Leu Glu Asp Leu Val Leu Pro

260 265 270

Glu Pro Val Ser Phe Leu Leu Val Leu Leu Gly Pro Glu Ala Pro His

275 280 285

Ile Asp Tyr Thr Gln Leu Gly Arg Ala Ala Ala Thr Leu Met Thr Glu

290 295 300

Arg Val Phe Arg Val Thr Ala Ser Leu Ala Gln Ser Arg Gly Glu Leu

305 310 315 320

Leu Ser Ser Leu Asp Ser Phe Leu Asp Cys Ser Leu Val Leu Pro Pro

325 330 335

Thr Glu Ala Pro Ser Glu Lys Ala Leu Leu Asn Leu Val Pro Val Gln

340 345 350

Lys Glu Leu Leu Arg Lys Arg Tyr Leu Pro Arg Pro Ala Lys Pro Asp

355 360 365

Pro Asn Leu Tyr Glu Ala Leu Ala Asp Gly Gly Lys Glu Gly Pro Gly

370 375 380

Asp Glu Asp Asp Pro Leu Arg Arg Thr Gly Arg Ile Phe Gly Gly Leu

385 390 395 400

Ile Arg Asp Ile Arg Arg Arg Tyr Pro Tyr Tyr Leu Ser Asp Ile Thr

405 410 415

Asp Ala Leu Ser Pro Gln Val Leu Ala Ala Val Ile Phe Ile Tyr Phe

420 425 430

Ala Ala Leu Ser Pro Ala Val Thr Phe Gly Gly Leu Leu Gly Glu Lys

435 440 445

Thr Arg Asn Leu Met Gly Val Ser Glu Leu Leu Ile Ser Thr Ala Val

450 455 460

Gln Gly Ile Leu Phe Ala Leu Leu Gly Ala Gln Pro Leu Leu Val Leu

465 470 475 480

Gly Phe Ser Gly Pro Leu Leu Val Phe Glu Glu Ala Phe Tyr Ser Phe

485 490 495

Cys Glu Ser Asn Asn Leu Glu Tyr Ile Val Gly Arg Ala Trp Ile Gly

500 505 510

Phe Trp Leu Ile Leu Leu Val Val Leu Val Val Ala Phe Glu Gly Ser

515 520 525

Phe Leu Val Gln Tyr Ile Ser Arg Tyr Thr Gln Glu Ile Phe Ser Phe

530 535 540

Leu Ile Ser Leu Ile Phe Ile Tyr Glu Thr Phe Ser Lys Leu Ile Lys

545 550 555 560

Ile Phe Gln Asp Tyr Pro Leu Gln Glu Ser Tyr Ala Pro Val Val Met

565 570 575

Lys Pro Lys Pro Gln Gly Pro Val Pro Asn Thr Ala Leu Leu Ser Leu

580 585 590

Val Leu Met Val Gly Thr Phe Leu Leu Ala Met Met Leu Arg Lys Phe

595 600 605

Lys Asn Ser Thr Tyr Phe Pro Gly Lys Leu Arg Arg Val Ile Gly Asp

610 615 620

Phe Gly Val Pro Ile Ser Ile Leu Ile Met Val Leu Val Asp Thr Phe

625 630 635 640

Ile Lys Asn Thr Tyr Thr Gln Lys Leu Ser Val Pro Asp Gly Leu Lys

645 650 655

Val Ser Asn Ser Ser Ala Arg Gly Trp Val Ile His Pro Leu Gly Leu

660 665 670

Tyr Asn His Phe Pro Lys Trp Met Met Phe Ala Ser Val Leu Pro Ala

675 680 685

Leu Leu Val Phe Ile Leu Ile Phe Leu Glu Ser Gln Ile Thr Thr Leu

690 695 700

Ile Val Ser Lys Pro Glu Arg Lys Met Ile Lys Gly Ser Gly Phe His

705 710 715 720

Leu Asp Leu Leu Leu Val Val Gly Met Gly Gly Val Ala Ala Leu Phe

725 730 735

Gly Met Pro Trp Leu Ser Ala Thr Thr Val Arg Ser Val Thr His Ala

740 745 750

Asn Ala Leu Thr Val Met Gly Lys Ala Ser Gly Pro Gly Ala Ala Ala

755 760 765

Gln Ile Gln Glu Val Lys Glu Gln Arg Ile Ser Gly Leu Leu Val Ser

770 775 780

Val Leu Val Gly Leu Ser Ile Leu Met Glu Pro Ile Leu Ser Arg Ile

785 790 795 800

Pro Leu Ala Val Leu Phe Gly Ile Phe Leu Tyr Met Gly Ile Thr Ser

805 810 815

Leu Ser Gly Ile Gln Leu Phe Asp Arg Ile Leu Leu Leu Phe Lys Pro

820 825 830

Pro Lys Tyr His Pro Asp Val Pro Phe Val Lys Arg Val Lys Thr Trp

835 840 845

Arg Met His Leu Phe Thr Gly Ile Gln Ile Ile Cys Leu Ala Val Leu

850 855 860

Trp Val Val Lys Ser Thr Pro Ala Ser Leu Ala Leu Pro Phe Val Leu

865 870 875 880

Ile Leu Thr Val Pro Leu Arg Arg Leu Leu Leu Pro Leu Ile Phe Arg

885 890 895

Glu Leu Glu Leu Gln Cys Leu Asp Gly Asp Asp Ala Lys Val Thr Phe

900 905 910

Asp Glu Ala Glu Gly Leu Asp Glu Tyr Asp Glu Val Pro Met Pro Val

915 920 925

<210>20

<211>199

<212>PRT

<213>Rattus sp.

<400>20

Met Ala Asn Arg Gly Pro Ser Tyr Gly Leu Ser Arg Glu Val Gln Gln

1 5 10 15

Lys Ile Glu Lys Gln Tyr Asp Pro Asp Leu Glu Gln Ile Leu Ile Gln

20 25 30

Trp Ile Thr Thr Gln Cys Arg Lys Gly Val Ser Gln Pro Gln Pro Gly

35 40 45

Arg Glu Asn Phe Gln Asn Trp Leu Lys Asp Gly Thr Val Leu Cys Glu

50 55 60

Leu Ile Asn Ser Leu Tyr Pro Glu Gly Gln Ala Pro Val Lys Lys Ile

65 70 75 80

Gln Ala Ser Thr Met Ala Phe Lys Gln Met Glu Gln Ile Ser Gln Phe

85 90 95

Leu Gln Ala Ala Glu Arg Tyr Gly Ile Asn Thr Thr Asp Ile Phe Gln

100 105 110

Thr Val Asp Leu Trp Glu Gly Lys Asn Met Ala Cys Val Gln Arg Thr

115 120 125

Leu Met Asn Leu Gly Gly Leu Ala Val Ala Arg Asp Asp Gly Leu Phe

130 135 140

Ser Gly Asp Pro Asn Trp Phe Pro Lys Lys Ser Lys Glu Asn Pro Arg

145 150 155 160

Asn Phe Ser Asp Asn Gln Leu Gln Glu Gly Lys Asn Val Ile Gly Leu

165 170 175

Gln Met Gly Thr Asn Arg Gly Ala Ser Gln Ala Gly Met Thr Gly Tyr

180 185 190

Gly Met Pro Arg Gln Ile Leu

195

<210>21

<211>247

<212>PRT

<213>Rattus sp.

<400>21

Met Ala Gly Ser Thr Thr Ile Glu Ala Val Lys Arg Lys Ile Gln Val

1 5 10 15

Leu Gln Gln Gln Ala Asp Asp Ala Glu Glu Arg Ala Glu Arg Leu Gln

20 25 30

Arg Glu Val Glu Gly Glu Arg Arg Ala Arg Glu Gln Ala Glu Ala Glu

35 40 45

Val Ala Ser Leu Asn Arg Arg Ile Gln Leu Val Glu Glu Glu Leu Asp

50 55 60

Arg Ala Gln Glu Arg Leu Ala Thr Ala Leu Gln Lys Leu Glu Glu Ala

65 70 75 80

Glu Lys Ala Ala Asp Glu Ser Glu Arg Gly Met Lys Val Ile Glu Asn

85 90 95

Arg Ala Leu Lys Asp Glu Glu Lys Met Glu Leu Gln Glu Ile Gln Leu

100 105 110

Lys Glu Ala Lys His Ile Ala Glu Glu Ala Asp Arg Lys Tyr Glu Glu

115 120 125

Val Ala Arg Lys Leu Val Ile Ile Glu Gly Asp Leu Glu Arg Thr Glu

130 135 140

Glu Arg Ala Glu Leu Ala Glu Ser Lys Cys Ser Glu Leu Glu Glu Glu

145 150 155 160

Leu Lys Asn Val Thr Asn Asn Leu Lys Ser Leu Glu Ala Gln Ala Glu

165 170 175

Lys Tyr Ser Gln Lys Glu Asp Lys Tyr Glu Glu Glu Ile Lys Ile Leu

180 185 190

Thr Asp Lys Leu Lys Glu Ala Glu Thr Arg Ala Glu Phe Ala Glu Arg

195 200 205

Ser Val Ala Lys Leu Glu Lys Thr Ile Asp Asp Leu Glu Glu Arg Leu

210 215 220

Tyr Ser Gln Leu Glu Arg Asn Arg Leu Leu Ser Asn Glu Leu Lys Leu

225 230 235 240

Thr Leu His Gly Leu Cys Asp

245

<210>22

<211>2541

<212>PRT

<213>Rattus sp.

<400>22

Met Val Ala Leu Ser Leu Arg Ile Ser Ile Gly Asn Val Val Lys Thr

1 5 10 15

Met Gln Phe Glu Pro Ser Thr Met Val Tyr Asp Ala Cys Arg Met Ile

20 25 30

Arg Glu Arg Ile Pro Glu Ala Leu Ala Gly Pro Pro Ser Asp Phe Gly

35 40 45

Leu Phe Leu Ser Asp Asp Asp Pro Lys Lys Gly Ile Trp Leu Glu Ala

50 55 60

Gly Lys Ala Leu Asp Tyr Tyr Met Leu Arg Asn Gly Asp Thr Met Glu

65 70 75 80

Tyr Arg Lys Lys Gln Arg Pro Leu Lys Ile Arg Met Leu Asp Gly Thr

85 90 95

Val Lys Thr Ile Met Val Asp Asp Ser Lys Thr Val Thr Asp Met Leu

100 105 110

Met Thr Ile Cys Ala Arg Ile Gly Ile Thr Asn His Asp Glu Tyr Ser

115 120 125

Leu Val Arg Glu Leu Met Glu Glu Lys Lys Asp Glu Gly Thr Gly Thr

130 135 140

Leu Arg Lys Asp Lys Thr Leu Leu Arg Asp Glu Lys Lys Met Glu Lys

145 150 155 160

Leu Lys Gln Lys Leu His Thr Asp Asp Glu Leu Asn Trp Leu Asp His

165 170 175

Gly Arg Thr Leu Arg Glu Gln Gly Val Glu Glu His Glu Thr Leu Leu

180 185 190

Leu Arg Arg Lys Phe Phe Tyr Ser Asp Gln Asn Val Asp Ser Arg Asp

195 200 205

Pro Val Gln Leu Asn Leu Leu Tyr Val Gln Ala Arg Asp Asp Ile Leu

210 215 220

Asn Gly Ser His Pro Val Ser Phe Asp Lys Ala Cys Glu Phe Ala Gly

225 230 235 240

Phe Gln Cys Gln Ile Gln Phe Gly Pro His Asn Glu Gln Lys His Lys

245 250 255

Ala Gly Phe Leu Asp Leu Lys Asp Phe Leu Pro Lys Glu Tyr Val Lys

260 265 270

Gln Lys Gly Glu Arg Lys Ile Phe Gln Ala His Lys Asn Cys Gly Gln

275 280 285

Met Ser Glu Ile Glu Ala Lys Val Arg Tyr Val Lys Leu Ala Arg Ser

290 295 300

Leu Lys Thr Tyr Gly Val Ser Phe Phe Leu Val Lys Glu Lys Met Lys

305 310 315 320

Gly Lys Asn Lys Leu Val Pro Arg Leu Leu Gly Ile Thr Lys Glu Cys

325 330 335

Val Met Arg Val Asp Glu Lys Thr Lys Glu Val Ile Gln Glu Trp Ser

340 345 350

Leu Thr Asn Ile Lys Arg Trp Ala Ala Ser Pro Lys Ser Phe Thr Leu

355 360 365

Asp Phe Gly Asp Tyr Gln Asp Gly Tyr Tyr Ser Val Gln Thr Thr Glu

370 375 380

Gly Glu Gln Ile Ala Gln Leu Ile Ala Gly Tyr Ile Asp Ile Ile Leu

385 390 395 400

Lys Lys Lys Lys Ser Lys Asp His Phe Gly Leu Glu Gly Asp Glu Glu

405 410 415

Ser Thr Met Leu Glu Asp Ser Val Ser Pro Lys Lys Ser Thr Val Leu

420 425 430

Gln Gln Gln Tyr Asn Arg Val Gly Lys Ala Glu His Gly Ser Val Ala

435 440 445

Leu Pro Ala Ile Met Arg Ser Gly Ala Ser Gly Pro Glu Asn Phe Gln

450 455 460

Val Gly Ser Met Pro Pro Ala Gln Gln Gln Val Thr Ser Gly Gln Met

465 470 475 480

His Arg Gly His Met Pro Pro Leu Thr Ser Ala Gln Gln Ala Leu Thr

485 490 495

Gly Thr Ile Asn Ser Ser Met Gln Ala Val Gln Ala Ala Gln Ala Ala

500 505 510

Leu Asp Asp Phe Asp Ala Leu Pro Pro Leu Gly Gln Asp Ala Ala Ser

515 520 525

Lys Ala Trp Arg Lys Asn Lys Met Asp Glu Ser Lys His Glu Ile His

530 535 540

Ser Gln Val Asp Ala Ile Thr Ala Gly Thr Ala Ser Val Val Asn Leu

545 550 555 560

Thr Ala Gly Asp Pro Ala Glu Thr Asp Tyr Thr Ala Val Gly Cys Ala

565 570 575

Val Thr Thr Ile Ser Ser Asn Leu Thr Glu Met Ser Arg Gly Val Lys

580 585 590

Leu Leu Ala Ala Leu Leu Glu Asp Glu Gly Gly Asn Gly Arg Pro Leu

595 600 605

Leu Gln Ala Ala Lys Gly Leu Ala Gly Ala Val Ser Glu Leu Leu Arg

610 615 620

Ser Ala Gln Pro Ala Ser Ala Glu Pro Arg Gln Asn Leu Leu Gln Ala

625 630 635 640

Ala Gly Asn Val Gly Gln Ala Ser Gly Glu Leu Leu Gln Gln Ile Gly

645 650 655

Glu Ser Asp Thr Asp Pro His Phe Gln Asp Ile Leu Met Gln Leu Ala

660 665 670

Lys Ala Val Ala Ser Ala Ala Ala Ala Leu Val Leu Lys Ala Lys Ser

675 680 685

Val Ala Gln Arg Thr Glu Asp Ser Gly Leu Gln Thr Gln Val Ile Ala

690 695 700

Ala Ala Thr Gln Cys Ala Leu Ser Thr Ser Gln Leu Val Ala Cys Thr

705 710 715 720

Lys Val Val Ala Pro Thr Ile Ser Ser Pro Val Cys Gln Glu Gln Leu

725 730 735

Val Glu Ala Gly Arg Leu Val Ala Lys Ala Val Glu Gly Cys Val Ser

740 745 750

Ala Ser Gln Ala Ala Thr Glu Asp Gly Gln Leu Leu Arg Gly Val Gly

755 760 765

Ala Ala Ala Thr Ala Val Thr Gln Ala Leu Asn Glu Leu Leu Gln His

770 775 780

Val Lys Ala His Ala Thr Gly Ala Gly Pro Ala Gly Arg Tyr Asp Gln

785 790 795 800

Ala Thr Asp Thr Ile Leu Thr Val Thr Glu Asn Ile Phe Ser Ser Met

805 810 815

Gly Asp A1a Gly Glu Met Val Arg Gln Ala Arg Ile Leu Ala Gln Ala

820 825 830

Thr Ser Asp Leu Val Asn Ala Ile Lys Ala Asp Ala Glu Gly Glu Ser

835 840 845

Asp Leu Glu Asn Ser Arg Lys Leu Leu Ser Ala Ala Lys Ile Leu Ala

850 855 860

Asp Ala Thr Ala Lys Met Val Glu Ala Ala Lys Gly Ala Ala Ala His

865 870 875 880

Pro Asp Ser Glu Glu Gln Gln Gln Arg Leu Arg Glu Ala Ala Glu Gly

885 890 895

Leu Arg Met Ala Thr Asn Ala Ala Ala Gln Asn Ala Ile Lys Lys Lys

900 905 910

Leu Val Gln Arg Leu Glu His Ala Ala Lys Gln Ala Ala Ala Ser Ala

915 920 925

Thr Gln Thr Ile Ala Ala Ala Gln His Ala Ala Ser Ala Pro Lys Ala

930 935 940

Ser Ala Gly Pro Gln Pro Leu Leu Val Gln Ser Cys Lys Ala Val Ala

945 950 955 960

Glu Gln Ile Pro Leu Leu Val Gln Gly Val Arg Gly Ser Gln Ala Gln

965 970 975

Pro Asp Ser Pro Ser Ala Gln Leu Ala Leu Ile Ala Ala Ser Gln Ser

980 985 990

Phe Leu Gln Pro Gly Gly Lys Met Val Ala Ala Ala Lys Ala Ser Val

995 1000 1005

Pro Thr Ile Gln Asp Gln Ala Ser Ala Met Gln Leu Ser Gln Cys

1010 1015 1020

Ala Lys Asn Leu Gly Thr Ala Leu Ala Glu Leu Arg Thr Ala Ala

1025 1030 1035

Gln Lys Ala Gln Glu Ala Cys Gly Pro Leu Glu Met Asp Ser Ala

1040 1045 1050

Leu Ser Val Val Gln Asn Leu Glu Lys Asp Leu Gln Glu Ile Lys

1055 1060 1065

Ala Ala Ala Arg Glu Gly Lys Leu Lys Pro Leu Pro Gly Glu Thr

1070 1075 1080

Met Glu Lys Cys Thr Gln Asp Leu Gly Asn Ser Thr Lys Ala Val

1085 1090 1095

Ser Ser Ala Ile Ala Lys Leu Leu Gly Glu Ile Ala Gln Gly Asn

1100 1105 1110

Glu Asn Tyr Ala Gly Ile Ala Ala Arg Asp Val Ala Gly Gly Leu

1115 1120 1125

Arg Ser Leu Ala Gln Ala Ala Arg Gly Val Ala Ala Leu Thr Thr

1130 1135 1140

Asp Pro Ala Val Gln Ala Ile Val Leu Asp Thr Ala Ser Asp Ala

1145 1150 1155

Leu Asp Lys Ala Ser Ser Leu Ile Glu Glu Ala Lys Lys Ala Ser

1160 1165 1170

Gly His Pro Gly Asp Pro Glu Ser Gln Gln Arg Leu Ala Gln Val

1175 1180 1185

Ala Lys Ala Val Thr Gln Ala Leu Asn Arg Cys Val Ser Cys Leu

1190 1195 1200

Pro Gly Gln Arg Asp Val Asp Asn Ala Leu Arg Ala Val Gly Asp

1205 1210 1215

Ala Ser Lys Arg Leu Leu Ser Asp Ser Leu Pro Pro Ser Thr Gly

1220 1225 1230

Thr Phe Gln Glu Ala Gln Ser Arg Leu Asn Glu Ala Ala Ala Gly

1235 1240 1245

Leu Asn Gln Ala Ala Thr Glu Leu Val Gln Ala Ser Arg Gly Thr

1250 1255 1260

Pro Gln Asp Leu Ala Arg Ala Ser Gly Arg Phe Gly Gln Asp Phe

1265 1270 1275

Ser Thr Phe Leu Glu Ala Gly Val Glu Met Ala Gly Gln Ala Pro

1280 1285 1290

Ser Gln Glu Asp Arg Ala Gln Val Val Ser Asn Leu Lys Gly Ile

1295 1300 1305

Ser Met Ser Ser Ser Lys Leu Leu Leu Ala Ala Lys Ala Leu Ser

1310 1315 1320

Thr Asp Pro Ala Ala Pro Asn Leu Lys Ser Gln Leu Ala Ala Ala

1325 1330 1335

Ala Arg Ala Val Thr Asp Ser Ile Asn Gln Leu Ile Thr Met Cys

1340 1345 1350

Thr Gln Gln Ala Pro Gly Gln Lys Glu Cys Asp Asn Ala Leu Arg

1355 1360 1365

Gln Leu Glu Thr Val Arg Glu Leu Leu Glu Asn Pro Val Gln Pro

1370 1375 1380

Ile Asn Asp Met Ser Tyr Phe Gly Cys Leu Asp Ser Val Met Glu

1385 1390 1395

Asn Ser Lys Val Leu Gly Glu Ala Met Thr Gly Ile Ser Gln Asn

1400 1405 1410

Ala Lys Asn Gly Asn Leu Pro Glu Phe Gly Asp Ala Ile Ala Thr

1415 1420 1425

Ala Ser Lys Ala Leu Cys Gly Phe Thr Glu Ala Ala Ala Gln Ala

1430 1435 1440

Ala Tyr Leu Val Gly Val Ser Asp Pro Asn Ser Gln Ala Gly Gln

1445 1450 1455

Gln Gly Leu Val Glu Pro Thr Gln Phe Ala Arg Ala Asn Gln Ala

1460 1465 1470

Ile Gln Met Ala Cys Gln Ser Leu Gly Glu Pro Gly Cys Thr Gln

1475 1480 1485

Ala Gln Val Leu Ser Ala Ala Thr Ile Val Ala Lys His Thr Ser

1490 1495 1500

Ala Leu Cys Asn Ser Cys Arg Leu Ala Ser Ala Arg Thr Ala Asn

1505 1510 1515

Pro Thr Ala Lys Arg Gln Phe Val Gln Ser Ala Lys Glu Val Ala

1520 1525 1530

Asn Ser Thr Ala Asn Leu Val Lys Thr Ile Lys Ala Leu Asp Gly

1535 1540 1545

Ala Phe Thr Glu Glu Asn Arg Ala Gln Cys Arg Ala Ala Thr Ala

1550 1555 1560

Pro Leu Leu Glu Ala Val Asp Asn Leu Ser Ala Phe Ala Ser Asn

1565 1570 1575

Pro Glu Phe Ser Ser Val Pro Ala Gln Ile Ser Pro Glu Gly Arg

1580 1585 1590

Ala Ala Met Glu Pro Ile Val Ile Ser Ala Lys Thr Met Leu Glu

1595 1600 1605

Ser Ala Gly Gly Leu Ile Gln Thr Ala Arg Ala Leu Ala Val Asn

1610 1615 1620

Pro Arg Asp Pro Pro Arg Trp Ser Val Leu Ala Gly His Ser Arg

1625 1630 1635

Thr Val Ser Asp Ser Ile Lys Lys Leu Ile Thr Ser Met Arg Asp

1640 1645 1650

Lys Ala Pro Gly Gln Leu Glu Cys Glu Thr Ala Ile Ala Ala Leu

1655 1660 1665

Asn Ser Cys Leu Arg Asp Leu Asp Gln Ala Ser Leu Ala Ala Val

1670 1675 1680

Ser Gln Gln Leu Ala Pro Arg Glu Gly Ile Ser Gln Glu Ala Leu

1685 1690 1695

His Thr Gln Met Leu Thr Ala Val Gln Glu Ile Ser His Leu Ile

1700 1705 1710

Glu Pro Leu Ala Ser Ala Ala Arg Ala Glu Ala Ser Gln Leu Gly

1715 1720 1725

His Lys Val Ser Gln Met Ala Gln Tyr Phe Glu Pro Leu Thr Leu

1730 1735 1740

Ala Ala Val Gly Ala Ala Ser Lys Thr Leu Ser His Pro Gln Gln

1745 1750 1755

Met Ala Leu Leu Asp Gln Thr Lys Thr Leu Ala Glu Ser Ala Leu

1760 1765 1770

Gln Leu Leu Tyr Thr Ala Lys Glu Ala Gly Gly Asn Pro Lys Gln

1775 1780 1785

Ala Ala Hi sThr Gln Glu Ala Leu Glu Glu Ala Val Gln Met Met

1790 1795 1800

Thr Glu Ala Val Glu Asp Leu Thr Thr Thr Leu Asn Glu Ala Ala

1805 1810 1815

Ser Ala Ala Gly Val Val Gly Gly Met Val Asp Ser Ile Thr Gln

1820 1825 1830

Ala Ile Asn Gln Leu Asp Glu Gly Pro Met Gly Glu Pro Glu Gly

1835 1840 1845

Ser Phe Val Asp Tyr Gln Thr Thr Met Val Arg Thr Ala Lys Ala

1850 1855 1860

Ile Ala Val Thr Val Gln Glu Met Val Thr Lys Ser Asn Thr Ser

1865 1870 1875

Pro Glu Glu Leu Gly Pro Leu Ala Asn Gln Leu Thr Ser Asp Tyr

1880 1885 1890

Gly Arg Leu Ala Ser Gln Ala Lys Pro Ala Ala Val Ala Ala Glu

1895 1900 1905

Asn Glu Glu Ile Gly Ala His Ile Lys His Arg Val Gln Glu Leu

1910 1915 1920

Gly His Gly Cys Ser Ala Leu Val Thr Lys Ala Gly Ala Leu Gln

1925 1930 1935

Cys Ser Pro Ser Asp Val Tyr Thr Lys Lys Glu Leu Ile Glu Cys

1940 1945 1950

Ala Arg Arg Val Ser Glu Lys Val Ser His Val Leu Ala Ala Leu

1955 1960 1965

Gln Ala Gly Asn Arg Gly Thr Gln Ala Cys Ile Thr Ala Ala Ser

1970 1975 1980

Ala Val Ser Gly Ile Ile Ala Asp Leu Asp Thr Thr Ile Met Phe

1985 1990 1995

Ala Thr Ala Gly Thr Leu Asn Arg Glu Gly Ala Glu Thr Phe Ala

2000 2005 2010

Asp His Arg Glu Gly Ile Leu Lys Thr Ala Lys Val Leu Val Glu

2015 2020 2025

Asp Thr Lys Val Leu Val Gln Asn Ala Ala Gly Ser Gln Glu Lys

2030 2035 2040

Leu Ala Gln Ala Ala Gln Ser Ser Val Ala Thr Ile Thr Arg Leu

2045 2050 2055

Ala Asp Val Val Lys Leu Gly Ala Ala Ser Leu Gly Ala Glu Asp

2060 2065 2070

Pro Glu Thr Gln Val Val Leu Ile Asn Ala Val Lys Asp Val Ala

2075 2080 2085

Lys Ala Leu Gly Asp Leu Ile Ser Ala Thr Lys Ala Ala Ala Gly

2090 2095 2100

Lys Val Gly Asp Asp Pro Ala Val Trp Gln Leu Lys Asn Ser Ala

2105 2110 2115

Lys Val Met Val Thr Asn Val Thr Ser Leu Leu Lys Thr Val Lys

2120 2125 2130

Ala Val Glu Asp Glu Ala Thr Lys Gly Thr Arg Ala Leu Glu Ala

2135 2140 2145

Thr Thr Glu His Ile Arg Gln Glu Leu Ala Val Phe Cys Ser Pro

2150 2155 2160

Glu Pro Pro Ala Lys Thr Ser Thr Pro Glu Asp Phe Ile Arg Met

2165 2170 2175

Thr Lys Gly Ile Thr Met Ala Thr Ala Lys Ala Val Ala Ala Gly

2180 2185 2190

Asn Ser Cys Arg Gln Glu Asp Val Ile Ala Thr Ala Asn Leu Ser

2195 2200 2205

Arg Arg Ala Ile Ala Asp Met Leu Arg Ala Cys Lys Glu Ala Ala

2210 2215 2220

Phe His Pro Glu Val Ala Pro Asp Val Arg Leu Arg Ala Leu His

2225 2230 2235

Phe Gly Arg Glu Cys Ala Asn Gly Tyr Leu Glu Leu Leu Asp His

2240 2245 2250

Val Leu Leu Thr Leu Gln Lys Pro Asn Pro Glu Leu Lys Gln Gln

2255 2260 2265

Leu Thr Gly His Ser Lys Arg Val Ala Gly Ser Val Thr Glu Leu

2270 2275 2280

Ile Gln Ala Ala Glu Ala Met Lys Gly Thr Glu Trp Val Asp Pro

2285 2290 2295

Glu Asp Pro Thr Val Ile Ala Glu Asn Glu Leu Leu Gly Ala Ala

2300 2305 2310

Ala Ala Ile Glu Ala Ala Ala Lys Lys Leu Glu Gln Leu Lys Pro

2315 2320 2325

Arg Ala Lys Pro Lys Glu Ala Asp Glu Ser Leu Asn Phe Glu Glu

2330 2335 2340

Gln Ile Leu Glu Ala Ala Lys Ser Ile Ala Ala Ala Thr Ser Ala

2345 2350 2355

Leu Val Lys Ala Ala Ser Ala Ala Gln Arg Glu Leu Val Ala Gln

2360 2365 2370

Gly Lys Val Gly Ala Ile Pro Ala Asn Ala Leu Asp Asp Gly Gln

2375 2380 2385

Trp Ser Gln Gly Leu Ile Ser Ala Ala Arg Met Val Ala Ala Ala

2390 2395 2400

Thr Asn Asn Leu Cys Glu Ala Ala Asn Ala Ala Val Gln Gly His

2405 2410 2415

Ala Ser Gln Glu Lys Leu Ile Ser Ser Ala Lys Gln Val Ala Ala

2420 2425 2430

Ser Thr Ala Gln Leu Leu Val Ala Cys Lys Val Lys Ala Asp Gln

2435 2440 2445

Asp Ser Glu Ala Met Lys Arg Leu Gln Ala Ala Gly Asn Ala Val

2450 2455 2460

Lys Arg Ala Ser Asp Asn Leu Val Lys Ala Ala Gln Lys Ala Ala

2465 2470 2475

Ala Phe Glu Asp Gln Glu Asn Glu Thr Val Val Val Lys Glu Lys

2480 2485 2490

Met Val Gly Gly Ile Ala Gln Ile Ile Ala Ala Gln Glu Glu Met

2495 2500 2505

Leu Arg Lys Glu Arg Glu Leu Glu Glu Ala Arg Lys Lys Leu Ala

2510 2515 2520

Gln Ile Arg Gln Gln Gln Tyr Lys Phe Leu Pro Ser Glu Leu Arg

2525 2530 2535

Asp Glu His

2540

<210>23

<211>191

<212>PRT

<213>Rattus sp.

<400>23

Met Ser Ala Ala Glu Val Gly Thr Phe Val Gln Arg Leu Arg Gly Leu

1 5 10 15

Met Ser Glu Ile Ala Ala Phe Pro Ala Pro Thr Ile Ala Ala Met Asp

20 25 30

Gly Phe Ala Leu Gly Gly Gly Leu Glu Leu Ala Leu Ala Cys Asp Leu

35 40 45

Arg Ile Ala Ala Ser Ser Ala Val Met Gly Leu Ile Glu Thr Thr Arg

50 55 60

Gly Leu Leu Pro Gly Ala Gly Gly Thr Gln Arg Leu Pro Arg Cys Leu

65 70 75 80

Gly Val Ala Leu Ala Lys Glu Leu Ile Phe Thr Gly Arg Arg Leu Asn

85 90 95

Gly Val Gln Ala His Glu Leu Gly Leu Val Asn His Ala Val Ala Gln

100 105 110

Asn Glu Glu Gly Asp Ala Ala Tyr His Arg Ala Leu Ala Leu Ala Gln

115 120 125

Glu Ile Leu Pro Gln Ala Pro Ile Ala Val Arg Leu Gly Lys Val Ala

130 135 140

Ile Asp Arg Gly Met Glu Val Asp Ile Ala Ser Gly Met Ala Ile Glu

145 150 155 160

His Met Cys Tyr Ala Gln Asn Ile Pro Thr Gln Asp Arg Leu Glu Gly

165 170 175

Met Ala Ala Phe Arg Glu Lys Arg Pro Pro Lys Phe Val Gly Lys

180 185 190

<210>24

<211>425

<212>PRT

<213>Rattus sp.

<400>24

Met Asn Tyr Ser Arg Phe Leu Thr Ala Thr Ser Leu Ala Arg Lys Thr

1 5 10 15

Ser Pro Ile Arg Ala Thr Val Glu Ile Met Ser Arg Ala Pro Lys Asp

20 25 30

Ile Ile Ser Leu Ala Pro Gly Ser Pro Asn Pro Lys Val Phe Pro Phe

35 40 45

Lys Ser Ala Val Phe Thr Val Glu Asn Gly Ser Thr Ile Arg Phe Glu

50 55 60

Gly Glu Met Phe Gln Arg Ala Leu Gln Tyr Ser Ser Ser Tyr Gly Ile

65 70 75 80

Pro Glu Leu Leu Ser Trp Leu Lys Gln Leu Gln Ile Lys Leu His Asn

85 90 95

Pro Pro Thr Val Asn Tyr Ser Pro Asn Glu Gly Gln Met Asp Leu Cys

100 105 110

Ile Thr Ser Gly Cys Gln Asp Gly Leu Cys Lys Val Phe Glu Met Leu

115 120 125

Ile Asn Pro Gly Asp Thr Val Leu Val Asn Glu Pro Leu Tyr Ser Gly

130 135 140

Ala Leu Phe Ala Met Lys Pro Leu Gly Cys Asn Phe Ile Ser Val Pro

145 150 155 160

Ser Asp Asp Cys Gly Ile Ile Pro Glu Gly Leu Lys Lys Val Leu Ser

165 170 175

Gln Trp Lys Pro Glu Asp Ser Lys Asp Pro Thr Lys Arg Thr Pro Lys

180 185 190

Phe Leu Tyr Thr Ile Pro Asn Gly Asn Asn Pro Thr Gly Asn Ser Leu

195 200 205

Thr Gly Asp Arg Lys Lys Glu Ile Tyr Glu Leu Ala Arg Lys Tyr Asp

210 215 220

Phe Leu Ile Ile Glu Asp Asp Pro Tyr Tyr Phe Leu Gln Phe Thr Lys

225 230 235 240

Pro Trp Glu Pro Thr Phe Leu Ser Met Asp Val Asp Gly Arg Val Ile

245 250 255

Arg Ala Asp Ser Leu Ser Lys Val Ile Ser Ser Gly Leu Arg Val Gly

260 265 270

Phe Ile Thr Gly Pro Lys Ser Leu Ile Gln Arg Ile Val Leu His Thr

275 280 285

Gln Ile Ser Ser Leu His Pro Cys Thr Leu Ser Gln Leu Met Ile Ser

290 295 300

Glu Leu Leu Tyr Gln Trp Gly Glu Glu Gly Phe Leu Ala His Val Asp

305 310 315 320

Arg Ala Ile Asp Phe Tyr Lys Asn Gln Arg Asp Phe Ile Leu Ala Ala

325 330 335

Ala Asp Lys Trp Leu Arg Gly Leu Ala Glu Trp His Val Pro Lys Ala

340 345 350

Gly Met Phe Leu Trp Ile Lys Val Asn Gly Ile Ser Asp Ala Lys Lys

355 360 365

Leu Ile Glu Glu Lys Ala Ile Glu Arg Glu Ile Leu Leu Val Pro Gly

370 375 380

Asn Ser Phe Phe Val Asp Asn Ser Ala Pro Ser Ser Phe Phe Arg Ala

385 390 395 400

Ser Phe Ser Gln Val Thr Pro Ala Gln Met Asp Leu Val Phe Gln Arg

405 410 415

Leu Ala Gln Leu Ile Lys Asp Val Ser

420 425

<210>25

<211>699

<212>PRT

<213>Rattus sp.

<400>25

Met Glu Val His Glu Leu Phe Arg Tyr Phe Arg Met Pro Glu Leu Ile

1 5 10 15

Asp Ile Arg Gln Tyr Val Arg Thr Leu Pro Thr Asn Thr Leu Met Gly

20 25 30

Phe Gly Ala Phe Ala Ala Leu Thr Thr Phe Trp Tyr Ala Thr Arg Pro

35 40 45

Lys Ala Leu Lys Pro Pro Cys Asp Leu Ser Met Gln Ser Val Glu Val

50 55 60

Thr Gly Thr Thr Glu Gly Val Arg Arg Ser Ala Val Leu Glu Asp Asp

65 70 75 80

Lys Leu Leu Leu Tyr Tyr Tyr Asp Asp Val Arg Thr Met Tyr Asp Gly

85 90 95

Phe Gln Arg Gly Ile Gln Val Ser Asn Asp Gly Pro Cys Leu Gly Ser

100 105 110

Arg Lys Pro Asn Gln Pro Tyr Glu Trp Ile Ser Tyr Lys Gln Val Ala

115 120 125

Glu Met Ala Glu Cys Ile Gly Ser Ala Leu Ile Gln Lys Gly Phe Lys

130 135 140

Pro Cys Ser Glu Gln Phe Ile Gly Ile Phe Ser Gln Asn Arg Pro Glu

145 150 155 160

Trp Val Thr Ile Glu Gln Gly Cys Phe Thr Tyr Ser Met Val Val Val

165 170 175

Pro Leu Tyr Asp Thr Leu Gly Thr Asp Ala Ile Thr Tyr Ile Val Asn

180 185 190

Lys Ala Glu Leu Ser Val Ile Phe Ala Asp Lys Pro Glu Lys Ala Lys

195 200 205

Leu Leu Leu Glu Gly Val Glu Asn Lys Leu Thr Pro Cys Leu Lys Ile

210 215 220

Ile Val Ile Met Asp Ser Tyr Asp Asn Asp Leu Val Glu Arg Gly Gln

225 230 235 240

Lys Cys Gly Val Glu Ile Ile Gly Leu Lys Ala Leu Glu Asp Leu Gly

245 250 255

Arg Val Asn Arg Thr Lys Pro Lys Pro Pro Glu Pro Glu Asp Leu Ala

260 265 270

Ile Ile Cys Phe Thr Ser Gly Thr Thr Gly Asn Pro Lys Gly Ala Met

275 280 285

Val Thr His Gln Asn Ile Met Asn Asp Cys Ser Gly Phe Ile Lys Ala

290 295 300

Thr Glu Ser Ala Phe Ile Ala Ser Pro Glu Asp Val Leu Ile Ser Phe

305 310 315 320

Leu Pro Leu Ala His Met Phe Glu Thr Val Val Glu Cys Val Met Leu

325 330 335

Cys His Gly Ala Lys Ile Gly Phe Phe Gln Gly Asp Ile Arg Leu Leu

340 345 350

Met Asp Asp Leu Lys Val Leu Gln Pro Thr Ile Phe Pro Val Val Pro

355 360 365

Arg Leu Leu Asn Arg Met Phe Asp Arg Ile Phe Gly Gln Ala Asn Thr

370 375 380

Ser Val Lys Arg Trp Leu Leu Asp Phe Ala Ser Lys Arg Lys Glu Ala

385 390 395 400

Glu Leu Arg Ser Gly Ile Val Arg Asn Asn Ser Leu Trp Asp Lys Leu

405 410 415

Ile Phe His Lys Ile Gln Ser Ser Leu Gly Gly Lys Val Arg Leu Met

420 425 430

Ile Thr Gly Ala Ala Pro Val Ser Ala Thr Val Leu Thr Phe Leu Arg

435 440 445

Ala Ala Leu Gly Cys Gln Phe Tyr Glu Gly Tyr Gly Gln Thr Glu Cys

450 455 460

Thr Ala Gly Cys Cys Leu Ser Leu Pro Gly Asp Trp Thr Ala Gly His

465 470 475 480

Val Gly Ala Pro Met Pro Cys Asn Tyr Ile Lys Leu Val Asp Val Glu

485 490 495

Asp Met Asn Tyr Gln Ala Ala Lys Gly Glu Gly Glu Val Cys Val Lys

500 505 510

Gly Ala Asn Val Phe Lys Gly Tyr Leu Lys Asp Pro Ala Arg Thr Ala

515 520 525

Glu Ala Leu Asp Lys Asp Gly Trp Leu His Thr Gly Asp Ile Gly Lys

530 535 540

Trp Leu Pro Asn Gly Thr Leu Lys Ile Ile Asp Arg Lys Lys His Ile

545 550 555 560

Phe Lys Leu Ala Gln Gly Glu Tyr Ile Ala Pro Glu Lys Ile Glu Asn

565 570 575

Ile Tyr Leu Arg Ser Glu Ala Val Ala Gln Val Phe Val His Gly Glu

580 585 590

Ser Leu Gln Ala Phe Leu Ile Ala Ile Val Val Pro Asp Val Glu Ile

595 600 605

Leu Pro Ser Trp Ala Gln Lys Arg Gly Phe Gln Gly Ser Phe Glu Glu

610 615 620

Leu Cys Arg Asn Lys Asp Ile Asn Lys Ala Ile Leu Glu Asp Met Val

625 630 635 640

Lys Leu Gly Lys Asn Ala Gly Leu Lys Pro Phe Glu Gln Val Lys Gly

645 650 655

Ile Ala Val His Pro Glu Leu Phe Ser Ile Asp Asn Gly Leu Leu Thr

660 665 670

Pro Thr Leu Lys Ala Lys Arg Pro Glu Leu Arg Asn Tyr Phe Arg Ser

675 680 685

Gln Ile Asp Glu Leu Tyr Ser Thr Ile Lys Ile

690 695

<210>26

<211>902

<212>PRT

<213>Rattus sp.

<400>26

Met Lys Ile Ala Val Ile Gly Gln Ser Leu Phe Gly Gln Glu Val Tyr

1 5 10 15

Cys Gln Leu Arg Lys Glu Gly His Glu Val Val Gly Val Phe Thr Ile

20 25 30

Pro Asp Lys Asp Gly Lys Ala Asp Pro Leu Gly Leu Glu Ala Glu Lys

35 40 45

Asp Gly Arg Ala Val Phe Lys Phe Pro Arg Trp Arg Ala Arg Gly Gln

50 55 60

Ala Leu Pro Glu Val Val Ala Lys Tyr Gln Ala Leu Gly Ala Glu Leu

65 70 75 80

Asn Val Leu Pro Phe Cys Ser Gln Phe Ile Pro Met Glu Val Ile Asn

85 90 95

Ala Pro Arg His Gly Ser Ile Ile Tyr His Pro Ser Leu Leu Pro Arg

100 105 110

His Arg Gly Ala Ser Ala Ile Asn Trp Thr Leu Ile His Gly Asp Lys

115 120 125

Lys Gly Gly Phe Thr Ile Phe Trp Ala Asp Asp Gly Leu Asp Thr Gly

130 135 140

Asp Leu Leu Leu Gln Lys Glu Cys Glu Val Leu Pro Asp Asp Thr Val

145 150 155 160

Ser Thr Leu Tyr Asn Arg Phe Leu Phe Pro Glu Gly Ile Lys Gly Met

165 170 175

Val Gln Ala Val Arg Leu Ile Ala Glu Gly Thr Ala Pro Arg Cys Pro

180 185 190

Gln Ser Glu Glu Gly Ala Thr Tyr Glu Gly Ile Gln Lys Lys Glu Thr

195 200 205

Ala Lys Ile Asn Trp Asp Gln Pro Ala Glu Ala Ile His Asn Trp Ile

210 215 220

Arg Gly Asn Asp Lys Val Pro Gly Ala Trp Thr Glu Ala Cys Gly Gln

225 230 235 240

Lys Leu Thr Phe Phe Asn Ser Thr Leu Asn Thr Ser Gly Leu Ser Thr

245 250 255

Gln Gly Glu Ala Leu Pro Ile Pro Gly Ala His Arg Pro Gly Val Val

260 265 270

Thr Lys Ala Gly Leu Ile Leu Phe Gly Asn Glu His Arg Met Leu Leu

275 280 285

Val Lys Asn Ile Gln Leu Glu Asp Gly Lys Met Met Pro Ala Ser Gln

290 295 300

Phe Phe Lys Gly Ser Ala Ser Ser Asp Leu Glu Leu Thr Glu Ala Glu

305 310 315 320

Leu Ala Thr Ala Glu Ala Val Arg Ser Ser Trp Met Arg Ile Leu Pro

325 330 335

Asn Val Pro Glu Val Glu Asp Ser Thr Asp Phe Phe Lys Ser Gly Ala

340 345 350

Ala Ser Val Asp Val Val Arg Leu Val Glu Glu Val Lys Glu Leu Cys

355 360 365

Asp Gly Leu Glu Leu Glu Asn Glu Asp Val Tyr Met Ala Thr Thr Phe

370 375 380

Arg Glu Phe Ile Gln Leu Leu Val Arg Lys Leu Arg Gly Glu Asp Asp

385 390 395 400

Glu Ser Glu Cys Val Ile Asn Tyr Val Glu Arg Ala Val Asn Lys Leu

405 410 415

Thr Leu Gln Met Pro Tyr Gln Leu Phe Ile Gly Gly Glu Phe Val Asp

420 425 430

Ala Glu Gly Ser Lys Thr Tyr Asn Thr Ile Asn Pro Thr Asp Gly Ser

435 440 445

Val Ile Cys Gln Val Ser Leu Ala Gln Val Ser Asp Val Asp Lys Ala

450 455 460

Val Ala Ala Ala Lys Glu Ala Phe Glu Asn Gly Leu Trp Gly Lys Ile

465 470 475 480

Asn Ala Arg Asp Arg Gly Arg Leu Leu Tyr Arg Leu Ala Asp Val Met

485 490 495

Glu Gln His Gln Glu Glu Leu Ala Thr Ile Glu Ala Leu Asp Arg Gly

500 505 510

Ala Val Tyr Thr Leu Ala Leu Lys Thr His Val Gly Met Ser Ile Gln

515 520 525

Thr Phe Arg Tyr Phe Ala Gly Trp Cys Asp Lys Ile Gln Gly Ala Thr

530 535 540

Ile Pro Ile Asn Gln Ala Arg Pro Asn Arg Asn Leu Thr Leu Thr Lys

545 550 555 560

Lys Glu Pro Val Gly Val Cys Gly Ile Val Ile Pro Trp Asn Tyr Pro

565 570 575

Leu Met Met Leu Ser Trp Lys Thr Ala Ala Cys Leu Ala Ala Gly Asn

580 585 590

Thr Val Val Ile Lys Pro Ala Gln Val Thr Pro Leu Thr Ala Leu Lys

595 600 605

Phe Ala Glu Leu Thr Leu Lys Ala Gly Ile Pro Lys Gly Val Val Asn

610 615 620

Ile Leu Pro Gly Ser Gly Ser Leu Val Gly Gln Arg Leu Ser Asp His

625 630 635 640

Pro Asp Val Arg Lys Ile Gly Phe Thr Gly Ser Thr Glu Val Gly Lys

645 650 655

His Ile Met Lys Ser Cys Ala Leu Ser Asn Val Lys Lys Val Ser Leu

660 665 670

Glu Leu Gly Gly Lys Ser Pro Leu Ile Ile Phe Ala Asp Cys Asp Leu

675 680 685

Asn Lys Ala Val Gln Met Gly Met Ser Ser Val Phe Phe Asn Lys Gly

690 695 700

Glu Asn Cys Ile Ala Ala Gly Arg Leu Phe Val Glu Glu Ser Ile His

705 710 715 720

Asn Gln Phe Val Gln Lys Val Val Glu Glu Val Glu Lys Met Lys Ile

725 730 735

Gly Asn Pro Leu Glu Arg Asp Thr Asn His Gly Pro Gln Asn His Glu

740 745 750

Ala His Leu Arg Lys Leu Val Glu Tyr Cys Gln Arg Gly Val Lys Glu

755 760 765

Gly Ala Thr Leu Val Cys Gly Gly Asn Gln Val Pro Arg Pro Gly Phe

770 775 780

Phe Phe Gln Pro Thr Val Phe Thr Asp Val Glu Asp His Met Tyr Ile

785 790 795 800

Ala Lys Glu Glu Ser Phe Gly Pro Ile Met Ile Ile Ser Arg Phe Ala

805 810 815

Asp Gly Asp Val Asp Ala Val Leu Ser Arg Ala Asn Ala Thr Glu Phe

820 825 830

Gly Leu Ala Ser Gly Val Phe Thr Arg Asp Ile Asn Lys Ala Leu Tyr

835 840 845

Val Ser Asp Lys Leu Gln Ala Gly Thr Val Phe Ile Asn Thr Tyr Asn

850 855 860

Lys Thr Asp Val Ala Ala Pro Phe Gly Gly Phe Lys Gln Ser Gly Phe

865 870 875 880

Gly Lys Asp Leu Gly Glu Ala Ala Leu Asn Glu Tyr Leu Arg Ile Lys

885 890 895

Thr Val Thr Phe Glu Tyr

900

<210>27

<211>412

<212>PRT

<213>Rattus sp.

<400>27

Met Ser Ser Lys Gly Ser Val Val Leu Ala Tyr Ser Gly Gly Leu Asp

1 5 10 15

Thr Ser Cys Ile Leu Val Trp Leu Lys Glu Gln Gly Tyr Asp Val Ile

20 25 30

Ala Tyr Leu Ala Asn Ile Gly Gln Lys Glu Asp Phe Glu Glu Ala Arg

35 40 45

Lys Lys Ala Leu Lys Leu Gly Ala Lys Lys Val Phe Ile Glu Asp Val

50 55 60

Ser Lys Glu Phe Val Glu Glu Phe Ile Trp Pro Ala Val Gln Ser Ser

65 70 75 80

Ala Leu Tyr Glu Asp Arg Tyr Leu Leu Gly Thr Ser Leu Ala Arg Pro

85 90 95

Cys Ile Ala Arg Lys Gln Val Glu Ile Ala Gln Arg Glu Gly Ala Lys

100 105 110

Tyr Val Ser His Gly Ala Thr Gly Lys Gly Asn Asp Gln Val Arg Phe

115 120 125

Glu Leu Thr Cys Tyr Ser Leu Ala Pro Gln Ile Lys Val Ile Ala Pro

130 135 140

Trp Arg Met Pro Glu Phe Tyr Asn Arg Phe Lys Gly Arg Asn Asp Leu

145 150 155 160

Met Glu Tyr Ala Lys Gln His Gly Ile Pro Ile Pro Val Thr Pro Lys

165 170 175

Ser Pro Trp Ser Met Asp Glu Asn Leu Met His Ile Ser Tyr Glu Ala

180 185 190

Gly Ile Leu Glu Asn Pro Lys Asn Gln Ala Pro Pro Gly Leu Tyr Thr

195 200 205

Lys Thr Gln Asp Pro Ala Lys Ala Pro Asn Thr Pro Asp Val Leu Glu

210 215 220

Ile Glu Phe Lys Lys Gly Val Pro Val Lys Val Thr Asn Val Lys Asp

225 230 235 240

Gly Thr Thr His Ser Thr Ser Leu Asp Leu Phe Met Tyr Leu Asn Glu

245 250 255

Val Ala Gly Lys His Gly Val Gly Arg Ile Asp Ile Val Glu Asn Arg

260 265 270

Phe Ile Gly Met Lys Ser Arg Gly Ile Tyr Glu Thr Pro Ala Gly Thr

275 280 285

Ile Leu Tyr His Ala His Leu Asp Ile Glu Ala Phe Thr Met Asp Arg

290 295 300

Glu Val Arg Lys Ile Lys Gln Gly Leu Gly Leu Lys Phe Ala Glu Leu

305 310 315 320

Val Tyr Thr Gly Phe Trp His Ser Pro Glu Cys Glu Phe Val Arg His

325 330 335

Cys Ile Asp Lys Ser Gln Glu Arg Val Glu Gly Lys Val Gln Val Ser

340 345 350

Val Phe Lys Gly Gln Val Tyr Ile Leu Gly Arg Glu Ser Pro Leu Ser

355 360 365

Leu Tyr Asn Glu Glu Leu Val Ser Met Asn Val Gln Gly Asp Tyr Glu

370 375 380

Pro Ile Asp Ala Thr Gly Phe Ile Asn Ile Asn Ser Leu Arg Leu Lys

385 390 395 400

Glu Tyr His Arg Leu Gln Ser Lys Val Thr Ala Lys

405 410

<210>28

<211>857

<212>PRT

<213>Rattus sp.

<400>28

Met Leu Arg Leu Gly Ala Leu Arg Leu Arg Gly Leu Ala Leu Arg Ser

1 5 10 15

Ser Gln Gly Arg Pro Ser Ser Ala Gly Leu Arg Glu Gly Gln Glu Ser

20 25 30

Pro Pro Ser Pro Pro Glu Trp Lys Asp Arg Ala Glu Thr Val Ile Ile

35 40 45

Gly Gly Gly Cys Val Gly Val Ser Leu Ala Tyr His Leu Ala Lys Ala

50 55 60

Gly Met Arg Asp Val Val Leu Leu Glu Lys Ser Glu Leu Thr Ala Gly

65 70 75 80

Ser Thr Trp His Ala Ala Gly Leu Thr Thr Tyr Phe His Pro Gly Ile

85 90 95

Asn Leu Lys Lys Ile His Tyr Asp Ser Ile Lys Leu Tyr Glu Arg Leu

100 105 110

Glu Glu Glu Thr Gly Gln Val Val Gly Phe His Gln Pro Gly Ser Ile

115 120 125

Arg Leu Ala Thr Thr Pro Glu Arg Val Asp Glu Phe Lys Tyr Gln Met

130 135 140

Thr Arg Thr Asn Trp His Ala Thr Glu Gln Tyr Ile Ile Glu Pro Glu

145 150 155 160

Lys Ile His Glu Leu Phe Pro Leu Leu Asn Met Asp Lys Ile Leu Ala

165 170 175

Gly Leu Tyr Asn Pro Gly Asp Gly His Ile Asp Pro Tyr Ser Leu Thr

180 185 190

Met Ala Leu Ala Thr Gly Ala Arg Lys Tyr Gly Ala Leu Leu Lys Tyr

195 200 205

Pro Ala Pro Val Thr Ser Leu Lys Pro Arg Pro Asp Gly Thr Trp Asp

210 215 220

Val Glu Thr Pro Gln Gly Ser Val Arg Ala Asn Arg Ile Val Asn Ala

225 230 235 240

Ala Gly Phe Trp Ala Arg Glu Val Gly Lys Met Ile Gly Leu Asp His

245 250 255

Pro Leu Ile Pro Val Gln His Gln Tyr Val Ile Thr Ser Thr Ile Pro

260 265 270

Glu Val Lys Ala Leu Lys Arg Glu Leu Pro Val Leu Arg Asp Leu Glu

275 280 285

Gly Ser Tyr Tyr Leu Arg Gln Glu Arg Asp Gly Leu Leu Phe Gly Pro

290 295 300

Tyr Glu Ser Gln Glu Lys Met Lys Leu Gln Ala Ser Trp Val Ala His

305 310 315 320

Gly Val Pro Pro Gly Phe Gly Lys Glu Leu Phe Glu Ser Asp Leu Asp

325 330 335

Arg Ile Thr Glu His Val Glu Ala Ala Met Glu Met Val Pro Val Leu

340 345 350

Lys Lys Ala Asp Ile Ile Asn Ile Val Asn Gly Pro Ile Thr Tyr Ser

355 360 365

Pro Asp Ile Leu Pro Met Val Gly Pro His Gln Gly Val Arg Asn Tyr

370 375 380

Trp Val Ala Ile Gly Phe Gly Tyr Gly Ile Ile His Ala Gly Gly Val

385 390 395 400

Gly Thr Tyr Leu Ser Asp Trp Ile Leu His Gly Glu Pro Pro Phe Asp

405 410 415

Leu Ile Glu Leu Asp Pro Asn Arg Tyr Gly Lys Trp Thr Thr Thr Gln

420 425 430

Tyr Thr Glu Ala Lys Ala Arg Glu Ser Tyr Gly Phe Asn Asn Ile Val

435 440 445

Gly Tyr Pro Lys Glu Glu Arg Phe Ala Gly Arg Pro Thr Gln Arg Val

450 455 460

Ser Gly Leu Tyr Lys Ile Leu Glu Ser Lys Cys Ser Met Gly Phe His

465 470 475 480

Ala Gly Trp Glu Gln Pro His Trp Phe Tyr Lys Pro Gly Gln Asp Thr

485 490 495

Gln Tyr Arg Pro Ser Phe Arg Arg Thr Asn Trp Phe Glu Pro Val Gly

500 505 510

Ser Glu Tyr Lys Gln Val Met Gln Arg Val Gly Val Ile Asp Leu Ser

515 520 525

Pro Phe Gly Lys Phe Asn Ile Lys Gly Gln Asp Ser Thr Gln Leu Leu

530 535 540

Asp His Leu Cys Ala Asn Val Ile Pro Lys Val Gly Phe Thr Asn Ile

545 550 555 560

Ser His Met Leu Thr Pro Arg Gly Arg Val Tyr Ala Glu Leu Thr Val

565 570 575

Ser His Gln Ser Pro Gly Glu Phe Leu Leu Ile Thr Gly Ser Gly Ser

580 585 590

Glu Leu His Asp Leu Arg Trp Ile Glu Glu Ala Ala Val Arg Gly Gly

595 600 605

Tyr Asp Val Glu Ile Arg Asn Ile Thr Asp Glu Leu Gly Val Leu Gly

610 615 620

Val Ala Gly Pro Tyr Ala Arg Arg Val Leu Gln Lys Leu Thr Ser Glu

625 630 635 640

Asp Leu Ser Asp Asp Val Phe Lys Phe Leu Gln Thr Lys Ser Leu Lys

645 650 655

Ile Ser Asp Ile Pro Val Thr Ala Ile Arg Ile Ser Tyr Thr Gly Glu

660 665 670

Leu Gly Trp Glu Leu Tyr His Arg Arg Glu Asp Ser Ala Ala Leu Tyr

675 680 685

Glu Arg Ile Met Asn Ala Gly Gln Glu Glu Gly Ile Asp Asn Phe Gly

690 695 700

Thr Tyr Ala Leu Asn Ala Leu Arg Leu Glu Lys Ala Phe Arg Ala Trp

705 710 715 720

Gly Ser Glu Met Asn Cys Asp Thr Asn Pro Leu Glu Ala Gly Leu Asp

725 730 735

Tyr Phe Ile Lys Leu Asn Lys Pro Ala Asn Phe Thr Gly Lys Gln Ala

740 745 750

Leu Lys Gln Ile Lys Ala Lys Gly Leu Lys Arg Arg Leu Val Cys Leu

755 760 765

Thr Leu Ala Thr Asp Asn Val Asp Pro Glu Gly Asn Glu Ser Val Trp

770 775 780

Tyr Lys Gly Lys Val Ile Gly Asn Thr Thr Ser Gly Ser Tyr Ser Tyr

785 790 795 800

Ser Ile Gln Lys Ser Leu Ala Phe Ala Tyr Val Pro Val Glu Leu Ser

805 810 815

Glu Val Gly Gln Gln Val Glu Val Glu Leu Leu Gly Lys Asn Tyr Pro

820 825 830

Ala Thr Ile Ile Gln Glu Pro Leu Val Leu Thr Glu Pro Thr Arg Thr

835 840 845

Arg Leu Gln Lys Asp Gly Arg Lys Ser

850 855

<210>29

<211>519

<212>PRT

<213>Rattus sp.

<400>29

Met Ala Pro Gln Glu Arg Leu Leu Ile Arg Gly Gly Arg Val Val Asn

1 5 10 15

Asp Asp Phe Ser Gln Val Ala Asp Val Leu Val Glu Asp Gly Val Val

20 25 30

Arg Ala Leu Gly Arg Asp Leu Leu Pro Pro Gly Asp Thr Ser Arg Gly

35 40 45

Leu Arg Ile Leu Asp Ala Ala Gly Lys Leu Val Leu Pro Gly Gly Ile

50 55 60

Asp Thr His Thr His Met Gln Phe Pro Phe Met Gly Ser Gln Ser Val

65 70 75 80

Asp Asp Phe His Gln Gly Thr Lys Ala Ala Leu Ala Gly Gly Thr Thr

85 90 95

Met Ile Ile Asp Phe Ala Ile Pro Gln Lys Gly Ser Ser Leu Ile Glu

100 105 110

Ala Phe Glu Thr Trp Arg Asn Trp Ala Asp Pro Lys Val Cys Cys Asp

115 120 125

Tyr Ser Leu His Val Ala Val Thr Trp Trp Ser Asp Lys Val Lys Glu

130 135 140

Glu Met Lys Thr Leu Ala Gln Asp Lys Gly Val Asn Ser Phe Lys Met

145 150 155 160

Phe Met Ala Tyr Lys Asp Leu Tyr Met Val Gln Asp Gln Gln Met Tyr

165 170 175

Ala Ala Phe Ser Gln Cys Lys Glu Ile Gly Ala Ile Ala Gln Val His

180 185 190

Ala Glu Asn Gly Asp Leu Ile Ala Glu Gly Ala Lys Lys Met Leu Ala

195 200 205

Leu Gly Ile Thr Gly Pro Glu Gly His Glu Leu Cys Arg Pro Glu Ala

210 215 220

Val Glu Ala Glu Ala Thr Leu Arg Ala Ile Thr Ile Ala Ser Ala Val

225 230 235 240

Asn Cys Pro Leu Tyr Ile Val His Val Met Ser Lys Ser Ala Ala Lys

245 250 255

Val Ile Ala Asp Ala Lys Arg Glu Gly Lys Val Val Tyr Gly Glu Pro

260 265 270

Ile Ala Ala Gly Leu Gly Thr Asp Gly Thr Gln Tyr Trp Asn Lys Glu

275 280 285

Trp Arg His Ala Ala His His Val Met Gly Pro Pro Leu Arg Pro Asp

290 295 300

Pro Ser Thr Pro Gly Phe Leu Met Asn Leu Leu Ala Asn Gly Asp Leu

305 310 315 320

Thr Thr Thr Gly Ser Asp Asn Cys Thr Phe Asn Thr Cys Gln Lys Ala

325 330 335

Leu Gly Lys Asp Asp Phe Thr Lys Ile Pro Asn Gly Val Asn Gly Val

340 345 350

Glu Asp Arg Met Ser Val Ile Trp Glu Lys Gly Val His Ser Gly Lys

355 360 365

Met Asp Glu Asn Arg Phe Val Ala Val Thr Ser Thr Asn Ala Ala Lys

370 375 380

Ile Phe Asn Leu Tyr Pro Lys Lys Gly Arg Ile Ala Val Gly Ser Asp

385 390 395 400

Ala Asp Met Val Ile Trp Asp Pro Glu Ala Thr Arg Thr Ile Ser Ala

405 410 415

Lys Thr His His Gln Ala Val Asn Phe Asn Ile Phe Glu Gly Met Val

420 425 430

Cys His Gly Val Pro Leu Val Thr Ile Ser Arg Gly Arg Val Val Tyr

435 440 445

Glu Ala Gly Val Phe Asp Val Thr Ala Gly His Gly Lys Phe Ile Pro

450 455 460

Arg Gln Pro Phe Ala Glu Phe Ile Tyr Lys Arg Val Lys Gln Arg Asp

465 470 475 480

Gln Thr Cys Thr Pro Ile Pro Val Lys Arg Ala Pro Tyr Lys Gly Glu

485 490 495

Val Ile Thr Leu Lys Pro Arg Glu Thr Lys Glu Asp Asp Thr Ala Gly

500 505 510

Thr Arg Met Gln Gly His Ser

515

<210>30

<211>885

<212>PRT

<213>Rattus sp.

<400>30

Met Ala Arg Gln Gly Cys Leu Gly Ser Phe Gln Val Ile Ser Leu Phe

1 5 10 15

Thr Phe Ala Ile Ser Val Asn Ile Cys Leu Gly Phe Thr Ala Ser Arg

20 25 30

Ile Lys Arg Ala Glu Trp Asp Glu Gly Pro Pro Thr Val Leu Ser Asp

35 40 45

Ser Pro Trp Thr Asn Thr Ser Gly Ser Cys Lys Gly Arg Cys Phe Glu

50 55 60

Leu Gln Glu Val Gly Pro Pro Asp Cys Arg Cys Asp Asn Leu Cys Lys

65 70 75 80

Ser Tyr Ser Ser Cys Cys His Asp Phe Asp Glu Leu Cys Leu Lys Thr

85 90 95

Val Arg Gly Trp Glu Cys Thr Lys Asp Arg Ser Gly Glu Val Arg Asn

100 105 110

Glu Glu Asn Ala Cys His Cys Pro Glu Asp Cys Leu Ser Arg Gly Asp

115 120 125

Cys Cys Thr Asn Tyr Gln Val Val Cys Lys Gly Glu Ser His Trp Val

130 135 140

Asp Asp Ala Ala Arg Asn Gln Ser Ser Glu Cys Leu Gln Val Cys Pro

145 150 155 160

Pro Pro Leu Ile Ile Phe Ser Val Asp Gly Phe Arg Ala Ser Tyr Met

165 170 175

Lys Lys Gly Ser Lys Val Met Pro Asn Ile Glu Lys Leu Arg Ser Cys

180 185 190

Gly Thr His Val Pro Tyr Thr Arg Pro Val Tyr Pro Thr Lys Thr Phe

195 200 205

Pro Asn Leu Tyr Thr Leu Ala Thr Gly Leu Tyr Pro Glu Ser His Gly

210 215 220

Ile Val Gly Asn Ser Met Tyr Asp Pro Val Phe Asp Ala Ser Phe His

225 230 235 240

Leu Arg Gly Arg Glu Lys Phe Asn His Arg Trp Trp Gly Gly Gln Pro

245 250 255

Leu Trp Ile Thr Ala Thr Lys Gln Gly Val Arg Ala Gly Thr Phe Phe

260 265 270

Trp Ser Val Ser Ile Pro His Glu Arg Arg Ile Leu Thr Ile Leu Gln

275 280 285

Trp Leu Ser Leu Pro Asp Asn Glu Arg Pro Ser Val Tyr Ala Phe Tyr

290 295 300

Ser Glu Gln Pro Asp Phe Ser Gly His Lys Tyr Gly Pro Phe Gly Pro

305 310 315 320

Glu Met Thr Asn Pro Leu Arg Glu Ile Asp Lys Thr Val Gly Gln Leu

325 330 335

Met Asp Gly Leu Lys Gln Leu Arg Leu His Arg Cys Val Asn Val Ile

340 345 350

Phe Val Gly Asp His Gly Met Glu Asp Val Thr Cys Asp Arg Thr Glu

355 360 365

Phe Leu Ser Asn Tyr Leu Thr Asn Val Asp Asp Ile Thr Leu Val Pro

370 375 380

Gly Thr Leu Gly Arg Ile Arg Ala Lys Ser Ile Asn Asn Ser Lys Tyr

385 390 395 400

Asp Pro Lys Thr Ile Ile Ala Asn Leu Thr Cys Lys Lys Pro Asp Gln

405 410 415

His Phe Lys Pro Tyr Met Lys Gln His Leu Pro Lys Arg Leu His Tyr

420 425 430

Ala Asn Asn Arg Arg Ile Glu Asp Ile His Leu Leu Val Asp Arg Arg

435 440 445

Trp His Val Ala Arg Lys Pro Leu Asp Val Tyr Lys Lys Pro Ser Gly

450 455 460

Lys Cys Phe Phe Gln Gly Asp His Gly Phe Asp Asn Lys Val Asn Ser

465 470 475 480

Met Gln Thr Val Phe Val Gly Tyr Gly Pro Thr Phe Lys Tyr Arg Thr

485 490 495

Lys Val Pro Pro Phe Glu Asn Ile Glu Leu Tyr Asn Val Met Cys Asp

500 505 510

Leu Leu Gly Leu Lys Pro Ala Pro Asn Asn Gly Thr His Gly Ser Leu

515 520 525

Asn His Leu Leu Arg Thr Asn Thr Phe Arg Pro Thr Met Pro Asp Glu

530 535 540

Val Ser Arg Pro Asn Tyr Pro Gly Ile Met Tyr Leu Gln Ser Glu Phe

545 550 555 560

Asp Leu Gly Cys Thr Cys Asp Asp Lys Val Glu Pro Lys Asn Lys Leu

565 570 575

Glu Glu Leu Asn Lys Arg Leu His Thr Lys Gly Ser Thr Glu Ala Glu

580 585 590

Thr Gly Lys Phe Arg Gly Ser Lys His Glu Asn Lys Lys Asn Leu Asn

595 600 605

Gly Ser Val Glu Pro Arg Lys Glu Arg His Leu Leu Tyr Gly Arg Pro

610 615 620

Ala Val Leu Tyr Arg Thr Ser Tyr Asp Ile Leu Tyr His Thr Asp Phe

625 630 635 640

Glu Ser Gly Tyr Ser Glu Ile Phe Leu Met Pro Leu Trp Thr Ser Tyr

645 650 655

Thr Ile Ser Lys Gln Ala Glu Val Ser Ser Ile Pro Glu His Leu Thr

660 665 670

Asn Cys Val Arg Pro Asp Val Arg Val Ser Pro Gly Phe Ser Gln Asn

675 680 685

Cys Leu Ala Tyr Lys Asn Asp Lys Gln Met Ser Tyr Gly Phe Leu Phe

690 695 700

Pro Pro Tyr Leu Ser Ser Ser Pro Glu Ala Lys Tyr Asp Ala Phe Leu

705 710 715 720

Val Thr Asn Met Val Pro Met Tyr Pro Ala Phe Lys Arg Val Trp Ala

725 730 735

Tyr Phe Gln Arg Val Leu Val Lys Lys Tyr Ala Ser Glu Arg Asn Gly

740 745 750

Val Asn Val Ile Ser Gly Pro Ile Phe Asp Tyr Asn Tyr Asp Gly Leu

755 760 765

Arg Asp Thr Glu Asp Glu Ile Lys Gln Tyr Val Glu Gly Ser Ser Ile

770 775 780

Pro Val Pro Thr His Tyr Tyr Ser Ile Ile Thr Ser Cys Leu Asp Phe

785 790 795 800

Thr Gln Pro Ala Asp Lys Cys Asp Gly Pro Leu Ser Val Ser Ser Phe

805 810 815

Ile Leu Pro His Arg Pro Asp Asn Asp Glu Ser Cys Asn Ser Ser Glu

820 825 830

Asp Glu Ser Lys Trp Val Glu Glu Leu Met Lys Met His Thr Ala Arg

835 840 845

Val Arg Asp Ile Glu His Leu Thr Gly Leu Asp Phe Tyr Arg Lys Thr

850 855 860

Ser Arg Ser Tyr Ser Glu Ile Leu Thr Leu Lys Thr Tyr Leu His Thr

865 870 875 880

Tyr Glu Ser Glu Ile

885

<210>31

<211>579

<212>PRT

<213>Rattus sp.

<400>31

Met Val Leu Ser Glu Val Trp Thr Thr Leu Ser Gly Val Ser Gly Val

1 5 10 15

Cys Leu Ala Cys Ser Leu Leu Ser Ala Ala Val Val Leu Arg Trp Thr

20 25 30

Gly Arg Gln Lys Ala Arg Gly Ala Ala Thr Arg Ala Arg Gln Lys Gln

35 40 45

Arg Ala Ser Leu Glu Thr Met Asp Lys Ala Val Gln Arg Phe Arg Leu

50 55 60

Gln Asn Pro Asp Leu Asp Ser Glu Ala Leu Leu Thr Leu Pro Leu Leu

65 70 75 80

Gln Leu Val Gln Lys Leu Gln Ser Gly Glu Leu Ser Pro Glu Ala Val

85 90 95

Phe Phe Thr Tyr Leu Gly Lys Ala Trp Glu Val Asn Lys Gly Thr Asn

100 105 110

Cys Val Thr Ser Tyr Leu Thr Asp Cys Glu Thr Gln Leu Ser Gln Ala

115 120 125

Pro Arg Gln Gly Leu Leu Tyr Gly Val Pro Val Ser Leu Lys Glu Cys

130 135 140

Phe Ser Tyr Lys Gly His Asp Ser Thr Leu Gly Leu Ser Leu Asn Glu

145 150 155 160

Gly Met Pro Ser Glu Ser Asp Cys Val Val Val Gln Val Leu Lys Leu

165 170 175

Gln Gly Ala Val Pro Phe Val His Thr Asn Val Pro Gln Ser Met Leu

180 185 190

Ser Phe Asp Cys Ser Asn Pro Leu Phe Gly Gln Thr Met Asn Pro Trp

195 200 205

Lys Ser Ser Lys Ser Pro Gly Gly Ser Ser Gly Gly Glu Gly Ala Leu

210 215 220

Ile Gly Ser Gly Gly Ser Pro Leu Gly Leu Gly Thr Asp Ile Gly Gly

225 230 235 240

Ser Ile Arg Phe Pro Ser Ala Phe Cys Gly Ile Cys Gly Leu Lys Pro

245 250 255

Thr Gly Asn Arg Leu Ser Lys Ser Gly Leu Lys Gly Cys Val Tyr Gly

260 265 270

Gln Thr Ala Val Gln Leu Ser Leu Gly Pro Met Ala Arg Asp Val Glu

275 280 285

Ser Leu Ala Leu Cys Leu Lys Ala Leu Leu Cys Glu Hls Leu Phe Thr

290 295 300

Leu Asp Pro Thr Val Pro Pro Leu Pro Phe Arg Glu Glu Val Tyr Arg

305 310 315 320

Ser Ser Arg Pro Leu Arg Val Gly Tyr Tyr Glu Thr Asp Asn Tyr Thr

325 330 335

Met Pro Ser Pro Ala Met Arg Arg Ala Leu Ile Glu Thr Lys Gln Arg

340 345 350

Leu Glu Ala Ala Gly His Thr Leu Ile Pro Phe Leu Pro Asn Asn Ile

355 360 365

Pro Tyr Ala Leu Glu Val Leu Ser Ala Gly Gly Leu Phe Ser Asp Gly

370 375 380

Gly Arg Ser Phe Leu Gln Asn Phe Lys Gly Asp Phe Val Asp Pro Cys

385 390 395 400

Leu Gly Asp Leu Ile Leu Ile Leu Arg Leu Pro Ser Trp Phe Lys Arg

405 410 415

Leu Leu Ser Leu Leu Leu Lys Pro Leu Phe Pro Arg Leu Ala Ala Phe

420 425 430

Leu Asn Ser Met Arg Pro Arg Ser Ala Glu Lys Leu Trp Lys Leu Gln

435 440 445

His Glu Ile Glu Met Tyr Arg Gln Ser Val Ile Ala Gln Trp Lys Ala

450 455 460

Met Asn Leu Asp Val Leu Leu Thr Pro Met Leu Gly Pro Ala Leu Asp

465 470 475 480

Leu Asn Thr Pro Gly Arg Ala Thr Gly Ala Ile Ser Tyr Thr Val Leu

485 490 495

Tyr Asn Cys Leu Asp Phe Pro Ala Gly Val Val Pro Val Thr Thr Val

500 505 510

Thr Ala Glu Asp Asp Ala Gln Met Glu Leu Tyr Lys Gly Tyr Phe Gly

515 520 525

Asp Ile Trp Asp Ile Ile Leu Lys Lys Ala Met Lys Asn Ser Val Gly

530 535 540

Leu Pro Val Ala Val Gln Cys Val Ala Leu Pro Trp Gln Glu Glu Leu

545 550 555 560

Cys Leu Arg Phe Met Arg Glu Val Glu Gln Leu Met Thr Pro Gln Lys

565 570 575

Gln Pro Ser

<210>32

<211>236

<212>PRT

<213>Rattus sp.

<400>32

Met Ser Ser Ser Ala Ala Ser Pro Leu Phe Ala Pro Gly Glu Asp Cys

1 5 10 15

Gly Pro Ala Trp Arg Ala Ala Pro Ala Ala Tyr Asp Thr Ser Asp Thr

20 25 30

His Leu Gln Ile Leu Gly Lys Pro Val Met Glu Arg Trp Glu Thr Pro

35 40 45

Tyr Met His Ser Leu Ala Ala Ala Ala Ala Ser Arg Gly Gly Arg Val

50 55 60

Leu Glu Val Gly Phe Gly Met Ala Ile Ala Ala Ser Arg Val Gln Gln

65 70 75 80

Ala Pro Ile Lys Glu His Trp Ile Ile Glu Cys Asn Asp Gly Val Phe

85 90 95

Gln Arg Leu Gln Asn Trp Ala Leu Lys Gln Pro His Lys Val Val Pro

100 105 110

Leu Lys Gly Leu Trp Glu Glu Glu Ala Pro Thr Leu Pro Asp Gly His

115 120 125

Phe Asp Gly Ile Leu Tyr Asp Thr Tyr Pro Leu Ser Glu Glu Thr Trp

130 135 140

His Thr His Gln Phe Asn Phe Ile Lys Thr His Ala Phe Arg Leu Leu

145 150 155 160

Lys Pro Gly Gly Ile Leu Thr Tyr Cys Asn Leu Thr Ser Trp Gly Glu

165 170 175

Leu Met Lys Ser Lys Tyr Thr Asp Ile Thr Ala Met Phe Glu Glu Thr

180 185 190

Gln Val Pro Ala Leu Leu Glu Ala Gly Phe Gln Arg Glu Asn Ile Cys

195 200 205

Thr Glu Val Met Ala Leu Val Pro Pro Ala Asp Cys Arg Tyr Tyr Ala

210 215 220

Phe Pro Gln Met Ile Thr Pro Leu Val Thr Lys His

225 230 235

<210>33

<211>440

<212>PRT

<213>Rattus sp.

<400>33

Met Val His Gly Tyr Lys Gly Val Gln Phe Gln Asn Trp Ala Lys Thr

1 5 10 15

Tyr Gly Cys Ser Pro Glu Val Tyr Tyr Gln Pro Thr Ser Val Glu Glu

20 25 30

Val Arg Glu Val Leu Ala Leu Ala Arg Glu Gln Lys Lys Lys Val Lys

35 40 45

Val Val Gly Gly Gly His Ser Pro Ser Asp Ile Ala Cys Thr Asp Gly

50 55 60

Phe Met Ile His Met Gly Lys Met Asn Arg Val Leu Gln Val Asp Lys

65 70 75 80

Glu Lys Lys Gln Ile Thr Val Glu Ala Gly Ile Leu Leu Ala Asp Leu

85 90 95

His Pro Gln Leu Asp Glu His Gly Leu Ala Met Ser Asn Leu Gly Ala

100 105 110

Val Ser Asp Val Thr Val Ala Gly Val Ile Gly Ser Gly Thr His Asn

115 120 125

Thr Gly Ile Lys His Gly Ile Leu Ala Thr Gln Val Val Ala Leu Thr

130 135 140

Leu Met Thr Ala Asp Gly Glu Val Leu Glu Cys Ser Glu Ser Arg Asn

145 150 155 160

Ala Asp Val Phe Gln Ala Ala Arg Val His Leu Gly Cys Leu Gly Ile

165 170 175

Ile Leu Thr Val Thr Leu Gln Cys Val Pro Gln Phe His Leu Gln Glu

180 185 190

Thr Ser Phe Pro Ser Thr Leu Lys Glu Val Leu Asp Asn Leu Asp Ser

195 200 205

His Leu Lys Arg Ser Glu Tyr Phe Arg Phe Leu Trp Phe Pro His Thr

210 215 220

Glu Asn Val SerIle Ile Tyr Gln Asp Hi s Thr Asn Lys Ala Pro Ser

225 230 235 240

Ser Ala Ser Asn Trp Phe Trp Asp Tyr Ala Ile Gly Phe Tyr Leu Leu

245 250 255

Glu Phe Leu Leu Trp Thr Ser Thr Tyr Leu Pro Cys Leu Val Gly Trp

260 265 270

Ile Asn Arg Phe Phe Phe Trp Met Leu Phe Asn Cys Lys Lys Glu Ser

275 280 285

Ser Asn Leu Ser His Lys Ile Phe Thr Tyr Glu Cys Arg Phe Lys Gln

290 295 300

His Val Gln Asp Trp Ala Ile Pro Arg Glu Lys Thr Lys Glu Ala Leu

305 310 315 320

Leu Glu Leu Lys Ala Met Leu Glu Ala His Pro Lys Val Val Ala His

325 330 335

Tyr Pro Val Glu Val Arg Phe Thr Arg Gly Asp Asp Ile Leu Leu Ser

340 345 350

Pro Cys Phe Gln Arg Asp Ser Cys Tyr Met Asn Ile Ile Met Tyr Arg

355 360 365

Pro Tyr Gly Lys Asp Val Pro Arg Leu Asp Tyr Trp Leu Ala Tyr Glu

370 375 380

Thr Ile Met Lys Lys Phe Gly Gly Arg Pro His Trp Ala Lys Ala His

385 390 395 400

Asn Cys Thr Arg Lys Asp Phe Glu Glu Met Tyr Pro Thr Phe His Lys

405 410 415

Phe Cys Asp Ile Arg Glu Lys Leu Asp Pro Thr Gly Met Phe Leu Asn

420 425 430

Ser Tyr Leu Glu Lys Val Phe Tyr

435 440

<210>34

<211>335

<212>PRT

<213>Rattus sp.

<400>34

Met Ala Ala Ser Leu Gly Phe Arg Gly Ala Ala Ser Gly Leu Arg Tyr

1 5 10 15

Trp Ser Gly Arg Arg Arg Pro Val Gly Ser Leu Ala Ala Val Cys Ser

20 25 30

Arg Ser Met Ala Ser Lys Thr Pro Val Gly Phe Ile Gly Leu Gly Asn

35 40 45

Met Gly Asn Pro Met Ala Lys Asn Leu Ile Lys His Gly Tyr Pro Leu

50 55 60

Ile Leu Tyr Asp Val Phe Pro Asp Val Cys Lys Glu Phe Lys Glu Ala

65 70 75 80

Gly Glu Gln Val Ala Ser Ser Pro Ala Asp Val Ala Glu Lys Ala Asp

85 90 95

Arg Ile Ile Thr Met Leu Pro Ser Ser Met Asn Ser Ile Glu Val Tyr

100 105 110

Ser Gly Ala Asn Gly Ile Leu Lys Lys Val Lys Lys Gly Ser Leu Leu

115 120 125

Ile Asp Ser Ser Thr Ile Asp Pro Ser Val Ser Lys Glu Leu Ala Lys

130 135 140

Glu Val Glu Lys Met Gly Ala Val Phe Met Asp Ala Pro Val Ser Gly

145 150 155 160

Gly Val Gly Ala Ala Arg Ser Gly Asn Leu Thr Phe Met Val Gly Gly

165 170 175

Val Glu Asn Glu Phe Ala Ala Ala Gln Glu Leu Leu Gly Cys Met Gly

180 185 190

Ser Asn Val Leu Tyr Cys Gly Ala Val Gly Ser Gly Gln Ser Ala Lys

195 200 205

Ile Cys Asn Asn Met Leu Leu Ala Ile Ser Met Ile Gly Thr Ala Glu

210 215 220

Ala Met Asn Leu Gly Ile Arg Ser Gly Leu Asp Pro Lys Leu Leu Ala

225 230 235 240

Lys Ile Leu Asn Met Ser Ser Gly Arg Cys Trp Ser Ser Asp Thr Tyr

245 250 255

Asn Pro Val Pro Gly Val Met Asp Gly Val Pro Ser Ser Asn Asn Tyr

260 265 270

Gln Gly Gly Phe Gly Thr Thr Leu Met Ala Lys Asp Leu Gly Leu Ala

275 280 285

Gln Asp Ser Ala Thr Ser Thr Lys Thr Pro Ile Leu Leu Gly Ser Val

290 295 300

Ala His Gln Ile Tyr Arg Met Met Cys Ser Lys Gly Tyr Ser Lys Lys

305 310 315 320

Asp Phe Ser Ser Val Phe Gln Tyr Leu Arg Glu Glu Glu Thr Phe

325 330 335

<210>35

<211>298

<212>PRT

<213>Rattus sp.

<400>35

Met Glu Glu Lys Gln Ile Leu Cys Val Gly Leu Val Val Leu Asp Ile

1 5 10 15

Ile Asn Val Val Asp Lys Tyr Pro Glu Glu Asp Thr Asp Arg Arg Cys

20 25 30

Leu Ser Gln Arg Trp Gln Arg Gly Gly Asn Ala Ser Asn Ser Cys Thr

35 40 45

Val Leu Ser Leu Leu Gly Ala Arg Cys Ala Phe Met Gly Ser Leu Ala

50 55 60

His Gly His Val Ala Asp Phe Leu Val Ala Asp Phe Arg Arg Arg Gly

65 70 75 80

Val Asp Val Ser Gln Val Ala Trp Gln Ser Gln Gly Asp Thr Pro Cys

85 90 95

Ser Cys Cys Ile Val Asn Asn Ser Asn Gly Ser Arg Thr Ile Ile Leu

100 105 110

Tyr Asp Thr Asn Leu Pro Asp Val Ser Ala Lys Asp Phe Glu Lys Val

115 120 125

Asp Leu Thr Arg Phe Lys Trp Ile His Ile Glu Gly Arg Asn Ala Ser

130 135 140

Glu Gln Val Lys Met Leu Gln Arg Ile Glu Gln Tyr Asn Ala Thr Gln

145 150 155 160

Pro Leu Gln Gln Lys Val Arg Val Ser Val Glu Ile Glu Lys Pro Arg

165 170 175

Glu Glu Leu Phe Gln Leu Phe Gly Tyr Gly Glu Val Val Phe Val Ser

180 185 190

Lys Asp Val Ala Lys His Leu Gly Phe Arg Ser Ala Gly Glu Ala Leu

195 200 205

Lys Gly Leu Tyr Ser Arg Val Lys Lys Gly Ala Thr Leu Ile Cys Ala

210 215 220

Trp Ala Glu Glu Gly Ala Asp Ala Leu Gly Pro Asp Gly Gln Leu Leu

225 230 235 240

His Ser Asp Ala Phe Pro Pro Pro Arg Val Val Asp Thr Leu Gly Ala

245 250 255

Gly Asp Thr Phe Asn Ala Ser Val Ile Phe Ser Leu Ser Lys Gly Asn

260 265 270

Ser Met Gln Glu Ala Leu Arg Phe Gly Cys Gln Val Ala Gly Lys Lys

275 280 285

Cys Gly Leu Gln Gly Phe Asp Gly Ile Val

290 295

<210>36

<211>464

<212>PRT

<213>Rattus sp.

<400>36

Met Glu Pro Ser Pro Leu Glu Leu Pro Val Asp Ala Val Arg Arg Ile

1 5 10 15

Ala Ala Glu Leu Asn Cys Asp Pro Thr Asp Glu Arg Val Ala Leu Arg

20 25 30

Leu Asp Glu Glu Asp Lys Leu Lys Arg Phe Lys Asp Cys Phe Tyr Ile

35 40 45

Pro Lys Met Arg Asp Leu Pro Ser Ile Asp Leu Ser Leu Val Asn Glu

50 55 60

Asp Asp Asn Ala Ile Tyr Phe Leu Gly Asn Ser Leu Gly Leu Gln Pro

65 70 75 80

Lys Met Val Lys Thr Tyr Leu Glu Glu Glu Leu Asp Lys Trp Ala Lys

85 90 95

Ile Gly Ala Tyr Gly His Glu Val Gly Lys Arg Pro Trp Ile Ile Gly

100 105 110

Asp Glu Ser Ile Val Thr Leu Met Lys Asp Ile Val Gly Ala His Glu

115 120 125

Lys Glu Ile Ala Leu Met Asn Ala Leu Thr Val Asn Leu His Leu Leu

130 135 140

Leu Leu Ser Phe Phe Lys Pro Thr Pro Lys Arg His Lys Ile Leu Leu

145 150 155 160

Glu Ala Lys Ala Phe Pro Ser Asp His Tyr Ala Ile Glu Ser Gln Ile

165 170 175

Gln Leu His Gly Leu Asp Val Glu Lys Ser Met Arg Met Ile Lys Pro

180 185 190

Arg Glu Gly Glu Glu Thr Leu Arg Met Glu Asp Ile Leu Glu Val Ile

195 200 205

Glu Lys Glu Gly Asp Ser Ile Ala Val Val Leu Phe Ser Gly Leu His

210 215 220

Phe Tyr Thr Gly Gln Leu Phe Asn Ile Pro Ala Ile Thr Gln Ala Gly

225 230 235 240

His Ala Lys Gly Cys Phe Val Gly Phe Asp Leu Ala His Ala Val Gly

245 250 255

Asn Val Glu Leu His Leu His Asp Trp Asp Val Asp Phe Ala Cys Trp

260 265 270

Cys Ser Tyr Lys Tyr Leu Asn Ser Gly Ala Gly Gly Leu Ala Gly Ala

275 280 285

Phe Ile His Glu Lys His Ala His Thr Ile Lys Pro Ala Leu Val Gly

290 295 300

Trp Phe Gly His Glu Leu Ser Thr Arg Phe Asn Met Asp Asn Lys Leu

305 310 315 320

Gln Leu Ile Pro Gly Val Asn Gly Phe Arg Ile Ser Asn Pro Pro Ile

325 330 335

Leu Leu Val Cys Ser Leu His Ala Ser Leu Glu Ile Phe Gln Gln Ala

340 345 350

Thr Met Thr Ala Leu Arg Arg Lys Ser Ile Leu Leu Thr Gly Tyr Leu

355 360 365

Glu Tyr Leu Leu Lys His Tyr His Gly Gly Asn Asp Thr Glu Asn Lys

370 375 380

Arg Pro Val Val Asn Ile Ile Thr Pro Ser Arg Ala Glu Glu Arg Gly

385 390 395 400

Cys Gln Leu Thr Leu Thr Phe Ser Ile Ser Lys Lys Gly Val Phe Lys

405 410 415

Glu Leu Glu Lys Arg Gly Val Val Cys Asp Lys Arg Glu Pro Glu Gly

420 425 430

Ile Arg Val Ala Pro Val Pro Leu Tyr Asn Ser Phe His Asp Val Tyr

435 440 445

Lys Phe Ile Arg Leu Leu Thr Ala Ile Leu Asp Ser Thr Glu Arg Asn

450 455 460

<210>37

<211>1178

<212>PRT

<213>Rattus sp.

<400>37

Met Leu Lys Phe Gln Thr Val Arg Gly Gly Leu Arg Leu Leu Gly Val

1 5 10 15

Arg Arg Ser Ser Thr Ala Pro Val Ala Ser Pro Asn Val Arg Arg Leu

20 25 30

Glu Tyr Lys Pro Ile Lys Lys Val Met Val Ala Asn Arg Gly Glu Ile

35 40 45

Ala Ile Arg Val Phe Arg Ala Cys Thr Glu Leu Gly Ile Arg Thr Val

50 55 60

Ala Val Tyr Ser Glu Gln Asp Thr Gly Gln Met His Arg Gln Lys Ala

65 70 75 80

Asp Glu Ala Tyr Leu Ile Gly Arg Gly Leu Ala Pro Val Gln Ala Tyr

85 90 95

Leu His Ile Pro Asp Ile Ile Lys Val Ala Lys Glu Asn Gly Val Asp

100 105 110

Ala Val His Pro Gly Tyr Gly Phe Leu Ser Glu Arg Ala Asp Phe Ala

115 120 125

Gln Ala Cys Gln Asp Ala Gly Val Arg Phe Ile Gly Pro Ser Pro Glu

130 135 140

Val Val Arg Lys Met Gly Asp Lys Val Glu Ala Arg Ala Ile Ala Ile

145 150 155 160

Ala Ala Gly Val Pro Val Val Pro Gly Thr Asn Ser Pro Ile Asn Ser

165 170 175

Leu His Glu Ala His Glu Phe Ser Asn Thr Tyr Gly Phe Pro Ile Ile

180 185 190

Phe Lys Ala Ala Tyr Gly Gly Gly Gly Arg Gly Met Arg Val Val His

195 200 205

Ser Tyr Glu Glu Leu Glu Glu Asn Tyr Thr Arg Ala Tyr Ser Glu Ala

210 215 220

Leu Ala Ala Phe Gly Asn Gly Ala Leu Phe Val Glu Lys Phe Ile Glu

225 230 235 240

Lys Pro Arg His Ile Glu Val Gln Ile Leu Gly Asp Gln Tyr Gly Asn

245 250 255

Ile Leu His Leu Tyr Glu Arg Asp Cys Ser Ile Gln Arg Arg His Gln

260 265 270

Lys Val Val Glu Ile Ala Pro Ala Thr His Leu Asp Pro Gln Leu Arg

275 280 285

Ser Arg Leu Thr Ser Asp Ser Val Lys Leu Ala Lys Gln Val Gly Tyr

290 295 300

Glu Asn Ala Gly Thr Val Glu Phe Leu Val Asp Lys His Gly Lys His

305 310 315 320

Tyr Phe Ile Glu Val Asn Ser Arg Leu Gln Val Glu His Thr Val Thr

325 330 335

Glu Glu Ile Thr Asp Val Asp Leu Val His Ala Gln Ile His Val Ser

340 345 350

Glu Gly Arg Ser Leu Pro Asp Leu Gly Leu Arg Gln Glu Asn Ile Arg

355 360 365

Ile Asn Gly Cys Ala Ile Gln Cys Arg Val Thr Thr Glu Asp Pro Ala

370 375 380

Arg Ser Phe Gln Pro Asp Thr Gly Arg Ile Glu Val Phe Arg Ser Gly

385 390 395 400

Glu Gly Met Gly Ile Arg Leu Asp Asn Ala Ser Ala Phe Gln Gly Ala

405 410 415

Val Ile Ser Pro His Tyr Asp Ser Leu Leu Val Lys Val Ile Ala His

420 425 430

Gly Lys Asp His Pro Thr Ala Ala Thr Lys Met Ser Arg Ala Leu Ala

435 440 445

Glu Phe Arg Val Arg Gly Val Lys Thr Asn Ile Pro Phe Leu Gln Asn

450 455 460

Val Leu Asn Asn Gln Gln Phe Leu Ala Gly Ile Val Asp Thr Gln Phe

465 470 475 480

Ile Asp Glu Asn Pro Glu Leu Phe Gln Leu Arg Pro Ala Gln Asn Arg

485 490 495

Ala Gln Lys Leu Leu His Tyr Leu Gly His Val Met Val Asn Gly Pro

500 505 510

Thr Thr Pro Ile Pro Val Lys Val Ser Pro Ser Pro Val Asp Pro Ile

515 520 525

Val Pro Val Val Pro Ile Gly Pro Pro Pro Ala Gly Phe Arg Asp Ile

530 535 540

Leu Leu Arg Glu Gly Pro Glu Gly Phe Ala Arg Ala Val Arg Asn His

545 550 555 560

Gln Gly Leu Leu Leu Met Asp Thr Thr Phe Arg Asp Ala His Gln Ser

565 570 575

Leu Leu Ala Thr Arg Val Arg Thr His Asp Leu Lys Lys Ile Ala Pro

580 585 590

Tyr Val Ala His Asn Phe Asn Asn Leu Phe Ser Ile Glu Asn Trp Gly

595 600 605

Gly Ala Thr Phe Asp Val Ala Met Arg Phe Leu Tyr Glu Cys Pro Trp

610 615 620

Arg Arg Leu Gln Glu Leu Arg Glu Leu Ile Pro Asn Ile Pro Phe Gln

625 630 635 640

Met Leu Leu Arg Gly Ala Asn Ala Val Gly Tyr Thr Asn Tyr Pro Asp

645 650 655

Asn Val Val Phe Lys Phe Cys Glu Val Ala Lys Glu Asn Gly Met Asp

660 665 670

Val Phe Arg Ile Phe Asp Ser Leu Asn Tyr Leu Pro Asn Met Leu Leu

675 680 685

Gly Met Glu Ala Ala Gly Ser Ala Gly Gly Val Val Glu Ala Ala Ile

690 695 700

Ser Tyr Thr Gly Asp Val Ala Asp Pro Ser Arg Thr Lys Tyr Ser Leu

705 710 715 720

Glu Tyr Tyr Met Gly Leu Ala Glu Glu Leu Val Arg Ala Gly Thr His

725 730 735

Ile Leu Cys Ile Lys Asp Met Ala Gly Leu Leu Lys Pro Ala Ala Cys

740 745 750

Thr Met Leu Val Ser Ser Leu Arg Asp Arg Phe Pro Asp Leu Pro Leu

755 760 765

His Ile His Thr His Asp Thr Ser Gly Ser Gly Val Ala Ala Met Leu

770 775 780

Ala Cys Ala Gln Ala Gly Ala Asp Val Val Asp Val Ala Val Asp Ser

785 790 795 800

Met Ser Gly Met Thr Ser Gln Pro Ser Met Gly Ala Leu Val Ala Cys

805 810 815

Thr Lys Gly Thr Pro Leu Asp Thr Glu Val Pro Leu Glu Arg Val Phe

820 825 830

Asp Tyr Ser Glu Tyr Trp Glu Gly Ala Arg Gly Leu Tyr Ala Ala Phe

835 840 845

Asp Cys Thr Ala Thr Met Lys Ser Gly Asn Ser Asp Val Tyr Glu Asn

850 855 860

Glu Ile Pro Gly Gly Gln Tyr Thr Asn Leu His Phe Gln Ala His Ser

865 870 875 880

Met Gly Leu Gly Ser Lys Phe Lys Glu Val Lys Lys Ala Tyr Val Glu

885 890 895

Ala Asn Gln Met Leu Gly Asp Leu Ile Lys Val Thr Pro Ser Ser Lys

900 905 910

Ile Val Gly Asp Leu Ala Gln Phe Met Val Gln Asn Gly Leu Ser Arg

915 920 925

Ala Glu Ala Glu Ala Gln Ala Glu Glu Leu Ser Phe Pro Arg Ser Val

930 935 940

Val Glu Phe Leu Gln Gly Tyr Ile Gly Ile Pro His Gly Gly Phe Pro

945 950 955 960

Glu Pro Phe Arg Ser Lys Val Leu Lys Asp Leu Pro Arg Ile Glu Gly

965 970 975

Arg Pro Gly Ala Ser Leu Pro Pro Leu Asn Leu Lys Glu Leu Glu Lys

980 985 990

Asp Leu Ile Asp Arg His Gly Glu Glu Val Thr Pro Glu Asp Val Leu

995 1000 1005

Ser Ala Ala Met Tyr Pro Asp Val Phe Ala Gln Phe Lys Asp Phe

1010 1015 1020

Thr Ala Thr Phe Gly Pro Leu Asp Ser Leu Asn Thr Arg Leu Phe

1025 1030 1035

Leu Gln Gly Pro Lys Ile Ala Glu Glu Phe Glu Val Glu Leu Glu

1040 1045 1050

Arg Gly Lys Thr Leu His Ile Lys Ala Leu Ala Val Ser Asp Leu

1055 1060 1065

Asn Arg Ala Gly Gln Arg Gln Val Phe Phe Glu Leu Asn Gly Gln

1070 1075 1080

Leu Arg Ser Ile Leu Val Lys Asp Thr Gln Ala Met Lys Glu Met

1085 1090 1095

His Phe His Pro Lys Ala Leu Lys Asp Val Lys Gly Gln Ile Gly

1100 1105 1110

Ala Pro Met Pro Gly Lys Val Ile Asp Val Lys Val Ala Ala Gly

1115 1120 1125

Ala Lys Val Val Lys Gly Gln Pro Leu Cys Val Leu Ser Ala Met

1130 1135 1140

Lys Met Glu Thr Val Val Thr Ser Pro Met Glu Gly Thr Ile Arg

1145 1150 1155

Lys Val His Val Thr Lys Asp Met Thr Leu Glu Gly Asp Asp Leu

1160 1165 1170

Ile Leu Glu Ile Glu

1175

<210>38

<211>407

<212>PRT

<213>Rattus sp.

<400>38

Met Arg Trp Phe Arg Ala Leu Leu Lys Asn Ala Ser Leu Ala Gly Ala

1 5 10 15

Pro Lys Tyr Ile Glu His Phe Ser Lys Phe Ser Pro Ser Pro Leu Ser

20 25 30

Met Lys Gln Phe Leu Asp Phe Gly Ser Ser Asn Ala Cys Glu Lys Thr

35 40 45

Ser Phe Thr Phe Leu Arg Gln Glu Leu Pro Val Arg Leu Ala Asn Ile

50 55 60

Met Lys Glu Ile Asn Leu Leu Pro Asp Arg Val Leu Ser Thr Pro Ser

65 70 75 80

Val Gln Leu Val Gln Ser Trp Tyr Val Gln Ser Leu Leu Asp Ile Met

85 90 95

Glu Phe Leu Asp Lys Asp Pro Glu Asp His Arg Thr Leu Ser Gln Phe

100 105 110

Thr Asp Ala Leu Val Thr Ile Arg Asn Arg His Asn Asp Val Val Pro

115 120 125

Thr Met Ala Gln Gly Val Leu Glu Tyr Lys Asp Thr Tyr Gly Asp Asp

130 135 140

Pro Val Ser Asn Gln Asn Ile Gln Tyr Phe Leu Asp Arg Phe Tyr Leu

145 150 155 160

Ser Arg Ile Ser Ile Arg Met Leu Ile Asn Gln His Thr Leu Ile Phe

165 170 175

Asp Gly Ser Thr Asn Pro Ala His Pro Lys His Ile Gly Ser Ile Asp

180 185 190

Pro Asn Cys Ser Val Ser Asp Val Val Lys Asp Ala Tyr Asp Met Ala

195 200 205

Lys Leu Leu Cys Asp Lys Tyr Tyr Met Ala Ser Pro Asp Leu Glu Ile

210 215 220

Gln Glu Val Asn Ala Thr Asn Ala Thr Gln Pro Ile His Met Val Tyr

225 230 235 240

Val Pro Ser His Leu Tyr His Met Leu Phe Glu Leu Phe Lys Asn Ala

245 250 255

Met Arg Ala Thr Val Glu Ser His Glu Ser Ser Leu Thr Leu Pro Pro

260 265 270

Ile Lys Ile Met Val Ala Leu Gly Glu Glu Asp Leu Ser Ile Lys Met

275 280 285

Ser Asp Arg Gly Gly Gly Val Pro Leu Arg Lys Ile Glu Arg Leu Phe

290 295 300

Ser Tyr Met Tyr Ser Thr Ala Pro Thr Pro Gln Pro Gly Thr Gly Gly

305 310 315 320

Thr Pro Leu Ala Gly Phe Gly Tyr Gly Leu Pro Ile Ser Arg Leu Tyr

325 330 335

Ala Lys Tyr Phe Gln Gly Asp Leu Gln Leu Phe Ser Met Glu Gly Phe

340 345 350

Gly Thr Asp Ala Val Ile Tyr Leu Lys Ala Leu Ser Thr Asp Ser Val

355 360 365

Glu Arg Leu Pro Val Tyr Asn Lys Ser Ala Trp Arg His Tyr Gln Thr

370 375 380

Ile Gln Glu Ala Gly Asp Trp Cys Val Pro Ser Thr Glu Pro Lys Asn

385 390 395 400

Thr Ser Thr Tyr Arg Val Ser

405

<210>39

<211>362

<212>PRT

<213>Rattus sp.

<400>39

Met Glu Val His Asn Val Ser Ala Pro Phe Asn Phe Ser Leu Pro Pro

1 5 10 15

Gly Phe Gly His Arg Ala Thr Asp Lys Ala Leu Ser Ile Ile Leu Val

20 25 30

Leu Met Leu Leu Leu Ile Met Leu Ser Leu Gly Cys Thr Met Glu Phe

35 40 45

Ser Lys Ile Lys Ala His Leu Trp Lys Pro Lys Gly Val Ile Val Ala

50 55 60

Leu Val Ala Gln Phe Gly Ile Met Pro Leu Ala Ala Phe Leu Leu Gly

65 70 75 80

Lys Ile Phe His Leu Ser Asn Ile Glu Ala Leu Ala Ile Leu Ile Cys

85 90 95

Gly Cys Ser Pro Gly Gly Asn Leu Ser Asn Leu Phe Thr Leu Ala Met

100 105 110

Lys Gly Asp Met Asn Leu Ser Ile Val Met Thr Thr Cys Ser Ser Phe

115 120 125

Ser Ala Leu Gly Met Met Pro Leu Leu Leu Tyr Val Tyr Ser Lys Gly

130 135 140

Ile Tyr Asp Gly Asp Leu Lys Asp Lys Val Pro Tyr Lys Gly Ile Met

145 150 155 160

Ile Ser Leu Val Ile Val Leu Ile Pro Cys Thr Ile Gly Ile Val Leu

165 170 175

Lys Ser Lys Arg Pro His Tyr Val Pro Tyr Ile Leu Lys Gly Gly Met

180 185 190

Ile Ile Thr Phe Leu Leu Ser Val Ala Val Thr Ala Leu Ser Val Ile

195 200 205

Asn Val Gly Asn Ser Ile Met Phe Val Met Thr Pro His Leu Leu Ala

210 215 220

Thr Ser Ser Leu Met Pro Phe Ser Gly Phe Leu Met Gly Tyr Ile Leu

225 230 235 240

Ser Ala Leu Phe Gln Leu Asn Pro Ser Cys Arg Arg Thr Ile Ser Met

245 250 255

Glu Thr Gly Phe Gln Asn Ile Gln Leu Cys Ser Thr Ile Leu Asn Val

260 265 270

Thr Phe Pro Pro Glu Val Ile Gly Pro Leu Phe Phe Phe Pro Leu Leu

275 280 285

Tyr Met Ile Phe Gln Leu Ala Glu Gly Leu Leu Ile Ile Ile Ile Phe

290 295 300

Arg Cys Tyr Glu Lys Ile Lys Pro Pro Lys Asp Gln Thr Lys Ile Thr

305 310 315 320

Tyr Lys Ala Ala Ala Thr Glu Asp Ala Thr Pro Ala Ala Leu Glu Lys

325 330 335

Gly Thr His Asn Gly Asn Ile Pro Pro Leu Gln Pro Gly Pro Ser Pro

340 345 350

Asn Gly Leu Asn Ser Gly Gln Met Ala Asn

355 360

<210>40

<211>429

<212>PRT

<213>Rattus sp.

<400>40

Met Ala Ala Gln Gly Tyr Gly Tyr Tyr Arg Thr Val Ile Phe Thr Ala

1 5 10 15

Met Phe Gly Gly Tyr Ser Leu Tyr Tyr Phe Asn Arg Lys Thr Phe Ser

20 25 30

Phe Val Met Pro Ser Leu Val Asp Glu Ile Ala Leu Asp Lys Asp Asp

35 40 45

Leu Gly Leu Ile Thr Ser Ser Gln Ser Ala Ala Tyr Ala Ile Ser Lys

50 55 60

Phe Val Ser Gly Val Leu Ser Asp Gln Met Ser Ala Arg Trp Leu Phe

65 70 75 80

Ser Ser Gly Leu Leu Leu Val Gly Leu Val Asn Val Val Phe Ser Trp

85 90 95

Ser Ser Thr Val Thr Ala Phe Ala Ala Leu Trp Phe Leu Asn Gly Leu

100 105 110

Ala Gln Gly Leu Gly Trp Pro Pro Cys Gly Lys Ile Leu Arg Lys Trp

115 120 125

Phe Glu Pro Ser Gln Phe Gly Thr Trp Trp Ala Val Leu Ser Thr Ser

130 135 140

Met Asn Leu Ala Gly Ser Leu Gly Pro Ile Leu Ala Thr Ile Leu Ala

145 150 155 160

Gln Ser Tyr Ser Trp Arg Ser Thr Leu Ala Leu Ser Gly Ser Leu Cys

165 170 175

Val Val Val Ser Phe Phe Cys Leu Leu Leu Ile His Asn Glu Pro Ala

180 185 190

Asp Val Gly Leu Arg Asn Leu Asp Pro Ala Pro Ser Lys Gly Lys Lys

195 200 205

Gly Ser Ser Lys Glu Glu Ser Thr Leu Gln Asp Leu Leu Leu Ser Pro

210 215 220

Tyr Leu Trp Val Leu Ser Thr Gly Tyr Leu Val Val Phe Gly Val Lys

225 230 235 240

Thr Cys Cys Thr Asp Trp Gly Gln Phe Phe Leu Ile Gln Glu Arg Gly

245 250 255

Gln Ser Ala Leu Val Gly Ser Ser Tyr Ile Ser Ala Leu Glu Val Gly

260 265 270

Gly Leu Val Gly Ser Ile Ala Ala Gly Tyr Leu Ser Asp Arg Ala Met

275 280 285

Ala Lys Ala Gly Leu Ser Val Tyr Gly Asn Pro Arg His Ser Leu Leu

290 295 300

Leu Leu Met Met Ala Gly Met Ala Ala Ser Met Phe Leu Phe Arg Val

305 310 315 320

Thr Val Thr Ser Asp Ser Pro Lys Ile Trp Ile Leu Val Leu Gly Ala

325 330 335

Val Phe Gly Phe Ser Ser Tyr Gly Pro Ile Ala Leu Phe Gly Val Ile

340 345 350

Ala Asn Glu Ser Ala Pro Pro Asn Leu Cys Gly Thr Ser His Ala Ile

355 360 365

Val Gly Leu Met Ala Asn Val Gly Gly Phe Leu Ala Gly Leu Pro Phe

370 375 380

Ser Thr Ile Ala Lys His Tyr Ser Trp Ser Thr Ala Phe Trp Val Ala

385 390 395 400

Glu Val Ile Cys Ile Ala Ser Thr Val Val Phe Phe Leu Leu Arg Asn

405 410 415

Ile Arg Thr Lys Met Gly Arg Val Ser Lys Lys Ala Glu

420 425

<210>41

<211>463

<212>PRT

<213>Rattus sp.

<400>41

Met Leu Cys Ser Glu Leu Glu Thr Gly Ala Trp Gly Ala Leu Ala Ala

1 5 10 15

Glu Leu Gly Ala Ser Glu Ala Ala Ser Val Ser Val Asp Gln Gly Ala

20 25 30

Gly Ser Ala Leu Leu Gly Leu Glu Ser Glu Ala Ala Trp Ala Ala Ser

35 40 45

Leu Phe Ala Ser Arg Pro Ala Ala Gly Ala Ser Val Phe Leu Ala Ser

50 55 60

Pro Pro Ser Trp Gly Ala Arg Ser Gly Ala Arg Val Pro Ser Ala Leu

65 70 75 80

Gly Ala Arg Leu Ala Gly Leu Gly Gly Leu Val Ala His Arg Gly Pro

85 90 95

Gly Pro Gly Arg Leu Leu Leu Arg His Trp Pro Gly Leu Gly Leu Leu

100 105 110

Leu Arg Gly Ala Leu Ala Leu Leu Gly Leu Gly Leu Gly Arg Leu Leu

115 120 125

Leu Thr Gly Arg Leu Leu Val Gly Leu Leu Phe Leu Ser Pro Cys Leu

130 135 140

Pro Ile Trp Ser Val Leu Gly Leu Leu Cys Ala Leu Leu Asp Leu Ser

145 150 155 160

Gly Val Gly Gly Arg Leu Gly Phe Ser Leu Leu Trp Gly Pro Leu Phe

165 170 175

Leu Gly Ala Arg Ala Phe Ser Leu Leu Val Phe Val Leu Gly Leu Leu

180 185 190

Leu Ile His Ile Val Thr Leu Leu Ala Gln Leu Ala Ser His His Gly

195 200 205

Val Pro Leu Leu Arg Gly Ala Asp Glu Lys Ser Ser Leu His Phe Phe

210 215 220

Lys Leu Tyr Leu Leu Pro Leu Pro His Asn Lys Leu Trp Ala Thr Asn

225 230 235 240

Gln Thr Pro Ile Asn Glu Arg Thr Glu Met Val Tyr Ser Phe Arg Gln

245 250 255

Leu Lys Gln Ala Ala Arg Ile Gln Gly Lys Arg Trp Thr His Pro Glu

260 265 270

Gly Gln Leu Gly Ser Ser Asn Ile Cys Val Pro Leu Thr His Leu Ser

275 280 285

Ser Ser Pro Lys Tyr Leu Tyr Val Ala Arg Asn Ala Lys Asp Cys Met

290 295 300

Val Ser Tyr Tyr His Phe Tyr Arg Met Ser Gln Val Leu Pro Asn Pro

305 310 315 320

Gly Thr Trp Asn Glu Tyr Phe Glu Thr Phe Ile Asn Gly Lys Val Ser

325 330 335

Cys Gly Ser Trp Phe Asp His Val Lys Gly Trp Trp Glu Ile Arg Asp

340 345 350

Arg Tyr Gln Ile Leu Phe Leu Phe Tyr Glu Asp Met Lys Arg Asp Pro

355 360 365

Lys Arg Glu Ile Gln Lys Val Met Gln Phe Met Gly Lys Asn Leu Asp

370 375 380

Glu Glu Val Val Asp Lys Ile Val Leu Glu Thr Ser Phe Glu Lys Met

385 390 395 400

Lys Asp Asn Pro Leu Thr Asn Phe Ser Thr Ile Pro Lys Thr Ile Met

405 410 415

Asp Gln Ser Ile Ser Pro Phe Met Arg Lys Gly Ile Val Gly Asp Trp

420 425 430

Lys Asn His Phe Thr Val Ala Gln Asn Glu Arg Phe Asp Glu Ile Tyr

435 440 445

Glu Gln Lys Met Asp Gly Thr Ser Leu Asn Phe Cys Met Glu Leu

450 455 460

<210>42

<211>161

<212>PRT

<213>Rattus sp.

<400>42

Met Asp Gln Glu Ala Val Gly Asn Val Val Leu Leu Ala Ile Val Thr

1 5 10 15

Leu Ile Ser Val Val Gln Asn Ala Phe Phe Ala His Lys Val Glu Leu

20 25 30

Glu Ser Lys Ala Gln Ser Gly Arg Ser Phe Gln Arg Thr Gly Thr Leu

35 40 45

Ala Phe Glu Arg Val Tyr Thr Ala Asn Gln Asn Cys Val Asp Ala Tyr

50 55 60

Pro Thr Phe Leu Val Val Leu Trp Thr Ala Gly Leu Leu Cys Ser Gln

65 70 75 80

Val Pro Ala Ala Phe Ala Gly Leu Met Tyr Leu Phe Val Arg Gln Lys

85 90 95

Tyr Phe Val Gly Tyr Leu Gly Glu Arg Thr Gln Ser Thr Pro Gly Tyr

100 105 110

Ile Phe Gly Lys Arg Ile Ile Leu Phe Leu Phe Leu Met Ser Leu Ala

115 120 125

Gly Ile Leu Asn His Tyr Leu Ile Phe Phe Phe Gly Ser Asp Phe Glu

130 135 140

Asn Tyr Ile Arg Thr Ile Thr Thr Thr Ile Ser Pro Leu Leu Leu Ile

145 150 155 160

Pro

<210>43

<211>180

<212>PRT

<213>Rattus sp.

<400>43

Met Ser Glu Ser Glu Leu Gln Leu Val Ala Arg Arg Ile Arg Ser Phe

1 5 10 15

Pro Asp Phe Pro Ile Pro Gly Val Leu Phe Arg Asp Ile Ser Pro Leu

20 25 30

Leu Lys Asp Pro Asp Ser Phe Arg Ala Ser Ile Arg Leu Leu Ala Gly

35 40 45

His Leu Lys Ser Thr His Gly Gly Lys Ile Asp Tyr Ile Ala Gly Leu

50 55 60

Asp Ser Arg Gly Phe Leu Phe Gly Pro Ser Leu Ala Gln Glu Leu Gly

65 70 75 80

Val Gly Cys Val Leu Ile Arg Lys Arg Gly Lys Leu Pro Gly Pro Thr

85 90 95

Val Ser Ala Ser Tyr Ser Leu Glu Tyr Gly Lys Ala Glu Leu Glu Ile

100 105 110

Gln Lys Asp Ala Leu Glu Pro Gly Gln Lys Val Val Ile Val Asp Asp

115 120 125

Leu Leu Ala Thr Gly Gly Thr Met Cys Ala Ala Cys Glu Leu Leu Ser

130 135 140

Gln Leu Arg Ala Glu Val Val Glu Cys Val Ser Leu Val Glu Leu Thr

145 150 155 160

Ser Leu Lys Gly Arg Glu Lys Leu Gly Pro Val Pro Phe Phe Ser Leu

165 170 175

Leu Gln Tyr Glu

180

<210>44

<211>220

<212>PRT

<213>Rattus sp.

<400>44

Met Gly Ser Lys Leu Ser Lys Lys Lys Lys Gly Tyr Asn Val Asn Asp

1 5 10 15

Glu Lys Ala Lys Asp Lys Asp Lys Lys Ala Glu Gly Ala Gly Thr Glu

20 25 30

Glu Glu Gly Thr Gln Lys Glu Ser Glu Pro Gln Ala Ala Ala Asp Ala

35 40 45

Thr Glu Val Lys Glu Ser Ala Glu Glu Lys Pro Lys Asp Ala Ala Asp

50 55 60

Gly Glu Ala Lys Ala Glu Glu Lys Glu Ala Asp Lys Ala Ala Ala Lys

65 70 75 80

Glu Glu Ala Pro Lys Ala Glu Pro Glu Lys Ser Glu Gly Ala Ala Glu

85 90 95

Glu Gln Pro Glu Pro Ala Pro Ala Pro Glu Gln Glu Ala Ala Ala Pro

100 105 110

Gly Pro Ala Ala Gly Gly Glu Ala Pro Lys Ala Gly Glu Ala Ser Ala

115 120 125

Glu Ser Thr Gly Ala Ala Asp Gly Ala Pro Gln Glu Glu Gly Glu Ala

130 135 140

Lys Lys Thr Glu Ala Pro Ala Ala Gly Pro Glu Ala Lys Ser Asp Ala

145 150 155 160

Ala Pro Ala Ala Ser Asp Ser Lys Pro Ser Thr Glu Pro Ala Pro Ser

165 170 175

Ser Lys Glu Thr Pro Ala Ala Ser Glu Ala Pro Ser Ser Ala Ala Lys

180 185 190

Ala Pro Ala Pro Ala Ala Pro Ala Ala Glu Pro Gln Ala Glu Ala Pro

195 200 205

Val Ala Ser Ser Glu Gln Ser Val Ala Val Lys Glu

210 215 220

<210>45

<211>169

<212>PRT

<213>Rattus sp.

<400>45

Met Ser Gln Ser Trp Val Pro Ala Val Gly Leu Thr Leu Val Pro Ser

1 5 10 15

Leu Gly Gly Phe Met Gly Ala Tyr Phe Val Arg Gly Glu Gly Leu Arg

20 25 30

Trp Tyr Ala Ser Leu Gln Lys Pro Ser Trp His Pro Pro Arg Trp Thr

35 40 45

Leu Ala Pro Ile Trp Gly Thr Leu Tyr Ser Ala Met Gly Tyr Gly Ser

50 55 60

Tyr Ile Ile Trp Lys Glu Leu Gly Gly Phe Thr Glu Glu Ala Met Val

65 70 75 80

Pro Leu Gly Leu Tyr Thr Gly Gln Leu Ala Leu Asn Trp Ala Trp Pro

85 90 95

Pro Ile Phe Phe Gly Ala Arg Gln Met Gly Trp Ala Leu Val Asp Leu

100 105 110

Met Leu Val Ser Gly Val Ala Thr Ala Thr Thr Leu Ala Trp His Arg

115 120 125

Val Ser Pro Pro Ala Ala Arg Leu Leu Tyr Pro Tyr Leu Ala Trp Leu

130 135 140

Ala Phe Ala Thr Met Leu Asn Tyr Tyr Val Trp Arg Asp Asn Ser Gly

145 150 155 160

Arg Arg Gly Gly Ser Arg Leu Thr Glu

165

<210>46

<211>277

<212>PRT

<213>Rattus sp.

<400>46

Met Ser Ser Asp Arg Pro Val Ala Leu Val Thr Gly Ala Asn Lys Gly

1 5 10 15

Ile Gly Phe Ala Ile Val Arg Asp Leu Cys Arg Lys Phe Leu Gly Asp

20 25 30

Val Val Leu Thr Ala Arg Asp Glu Ser Arg Gly His Glu Ala Val Lys

35 40 45

Gln Leu Gln Thr Glu Gly Leu Ser Pro Arg Phe His Gln Leu Asp Ile

50 55 60

Asp Asn Pro Gln Ser Ile Arg Ala Leu Arg Asp Phe Leu Leu Gln Glu

65 70 75 80

Tyr Gly Gly Leu Asn Val Leu Val Asn Asn Ala Gly Ile Ala Phe Lys

85 90 95

Val Val Asp Pro Thr Pro Phe His Ile Gln Ala Glu Val Thr Met Lys

100 105 110

Thr Asn Phe Phe Gly Thr Gln Asp Val Cys Lys Glu Leu Leu Pro Ile

115 120 125

Ile Lys Pro Gln Gly Arg Val Val Asn Val Ser Ser Ser Val Ser Leu

130 135 140

Arg Ala Leu Lys Ser Cys Ser Pro Glu Leu Gln Gln Lys Phe Arg Ser

145 150 155 160

Glu Thr Ile Thr Glu Glu Glu Leu Val Gly Leu Met Asn Lys Phe Ile

165 170 175

Glu Asp Ala Lys Lys Gly Val His Ala Lys Glu Gly Trp Pro Asn Ser

180 185 190

Ala Tyr Gly Val Thr Lys Ile Gly Val Thr Val Leu Ser Arg Ile Tyr

195 200 205

Ala Arg Lys Leu Asn Glu Glu Arg Arg Glu Asp Lys Ile Leu Leu Asn

210 215 220

Ala Cys Cys Pro Gly Trp Val Arg Thr Asp Met Ala Gly Pro Lys Ala

225 230 235 240

Thr Lys Ser Pro Glu Glu Gly Ala Glu Thr Pro Val Tyr Leu Ala Leu

245 250 255

Leu Pro Pro Gly Ala Glu Gly Pro His Gly Gln Phe Val Gln Asp Lys

260 265 270

Lys Val Glu Pro Trp

275

<210>47

<211>303

<212>PRT

<213>Rattus sp.

<400>47

Met Trp Pro Leu Ala Ala Ala Leu Leu Leu Gly Ser Cys Cys Cys Gly

1 5 10 15

Ser Ala Gln Leu Leu Leu Ser Lys Val Lys Ser Val Glu Phe Thr Ser

20 25 30

Cys Asn Asp Thr Val Val Ile Pro Cys Lys Val Leu Asn Val Glu Ala

35 40 45

Gln Ser Thr Asp Glu Met Phe Val Lys Trp Lys Leu Asn Lys Ser Tyr

50 55 60

Ile Phe Ile Tyr Asp Gly Asn Lys Asn Ser Thr Thr Arg Glu Gln Asn

65 70 75 80

Phe Thr Ser Ala Lys Ile Ser Val Ser Asp Leu Leu Lys Gly Ile Ala

85 90 95

Ser Leu Thr Met Asp Thr His Glu Ala Val Val Gly Asn Tyr Thr Cys

100 105 110

Glu Val Thr Glu Leu Ser Arg Glu Gly Lys Thr Val Ile Glu Leu Lys

115 120 125

Asn Arg Pro Val Ser Trp Phe Ser Thr Asn Glu Lys Ile Leu Ile Val

130 135 140

Ile Phe Pro Ile Leu Ala Ile Leu Leu Phe Trp Gly Lys Phe Gly Ile

145 150 155 160

Leu Thr Leu Lys Tyr Lys Ser Ser His Thr Asn Lys Arg Ile Ile Leu

165 170 175

Leu Leu Val Ala Gly Leu Ala Leu Thr Leu Ile Val Val Val Gly Ala

180 185 190

Ile Leu Phe Ile Pro Gly Glu Lys Pro Val Lys Asn Ala Ser Gly Leu

195 200 205

Gly Leu Ile Val Ile Ser Thr Gly Ile Leu Ile Leu Leu Gln Tyr Asn

210 215 220

Val Phe Met Thr Ala Phe Gly Met Thr Ser Phe Thr Ile Ala Ile Leu

225 230 235 240

Ile Thr Gln Val Leu Gly Tyr Val Leu Ala Val Val Gly Met Cys Leu

245 250 255

Cys Ile Met Ala Cys Glu Pro Val Hi s Gly Pro Leu Leu Ile Ser Gly

260 265 270

Leu Gly Ile Ile Ala Leu Ala Glu Leu Leu Gly Leu Val Tyr Met Lys

275 280 285

Phe Val Ala Ser Asn Gln Arg Thr Ile Gln Pro Pro Arg Asn Asn

290 295 300

<210>48

<211>328

<212>PRT

<213>Rattus sp.

<400>48

Met Arg Ser His Thr Gly Leu Arg Ala Leu Val Ala Pro Gly Cys Ser

1 5 10 15

Leu Leu Leu Leu Tyr Leu Leu Ala Ala Thr Arg Pro Asp Arg Ala Val

20 25 30

Gly Asp Pro Ala Asp Ser Ala Phe Thr Ser Leu Pro Val Arg Glu Glu

35 40 45

Met Met Ala Lys Tyr Ala Asn Leu Ser Leu Glu Thr Tyr Asn Ile Ser

50 55 60

Leu Thr Glu Gln Thr Arg Val Ser Glu Gln Asn Ile Thr Leu Glu Arg

65 70 75 80

Pro Ser His Leu Glu Leu Glu Cys Thr Phe Thr Ala Thr Glu Asp Val

85 90 95

Met Ser Met Asn Val Thr Trp Lys Lys Asp Asp Ala Leu Leu Glu Thr

100 105 110

Thr Asp Gly Phe Asn Thr Thr Lys Met Gly Asp Thr Leu Tyr Ser Gln

115 120 125

Tyr Arg Phe Thr Val Phe Asn Ser Lys Gln Met Gly Lys Tyr Ser Cys

130 135 140

Phe Leu Gly Glu Glu Leu Arg Gly Thr Phe Asn Ile Arg Val Pro Lys

145 150 155 160

Val His Gly Lys Asn Lys Pro Leu Ile Thr Tyr Val Gly Asp Ser Thr

165 170 175

Val Leu Lys Cys Glu Cys Gln Asn Cys Leu Pro Leu Asn Trp Thr Trp

180 185 190

Tyr Met Ser Asn Gly Thr Ala Gln Val Pro Ile Asp Val His Val Asn

195 200 205

Asp Lys Phe Asp Ile Asn Gly Ser Tyr Ala Asn Glu Thr Lys Leu Lys

210 215 220

Val Lys His Leu Leu Glu Glu Asp Gly Gly Ser Tyr Trp Cys Arg Ala

225 230 235 240

Ala Phe Pro Leu Gly Glu Ser Glu Glu His Ile Lys Leu Val Val Leu

245 250 255

Ser Phe Met Val Pro Leu Lys Pro Phe Leu Ala Ile Ile Ala Glu Val

260 265 270

Ile Leu Leu Val AlaIle Ile Leu Leu Cy s Glu Val Tyr Thr Gln Lys

275 280 285

Lys Lys Asn Asp Pro Asp Asp Gly Lys Glu Phe Glu Gln Ile Glu Gln

290 295 300

Leu Lys Ser Asp Asp Ser Asn Gly Ile Glu Asn Asn Val Pro Arg Tyr

305 310 315 320

Arg Lys Thr Asp Ser Gly Asp Gln

325

<210>49

<211>578

<212>PRT

<213>Rattus sp.

<400>49

Met Ala Pro Ser Pro Arg Pro Gln His Val Leu His Trp Lys Glu Ala

1 5 10 15

His Ser Phe Tyr Leu Leu Ser Pro Leu Met Gly Phe Leu Ser Arg Ala

20 25 30

Trp Ser Arg Leu Arg Gly Pro Glu Val Ser Glu Ala Trp Leu Ala Glu

35 40 45

Thr Val Ala Gly Ala Asn Gln Ile Glu Ala Asp Ala Leu Leu Thr Pro

50 55 60

Pro Pro Val Ser Glu Asn His Leu Pro Leu Arg Glu Thr Glu Gly Asn

65 70 75 80

Gly Thr Pro Glu Trp Ser Lys Ala Ala Gln Arg Leu Cys Leu Asp Val

85 90 95

Glu Ala Gln Ser Ser Pro Pro Lys Thr Trp Gly Leu Ser Asp Ile Asp

100 105 110

Glu His Asn Gly Lys Pro Gly Gln Asp Gly Leu Arg Glu Gln Glu Val

115 120 125

Glu His Thr Ala Gly Leu Pro Thr Leu Gln Pro Leu His Leu Gln Gly

130 135 140

Ala Asp Lys Lys Val Gly Glu Val Val Ala Arg Glu Glu Gly Val Ser

145 150 155 160

Glu Leu Ala Tyr Pro Thr Ser His Trp Glu Gly Gly Pro Ala Glu Asp

165 170 175

Glu Glu Asp Thr Glu Thr Val Lys Lys Ala His Gln Ala Ser Ala Ala

180 185 190

Ser Ile Ala Pro Gly Tyr Lys Pro Ser Thr Ser Val Tyr Cys Pro Gly

195 200 205

Glu Ala Glu His Arg Ala Thr Glu Glu Lys Gly Thr Asp Asn Lys Ala

210 215 220

Glu Pro Ser Gly Ser His Ser Arg Val Trp Glu Tyr His Thr Arg Glu

225 230 235 240

Arg Pro Lys Gln Glu Gly Glu Thr Lys Pro Glu Gln His Arg Ala Gly

245 250 255

Gln Ser His Pro Cys Gln Asn Ala Glu Ala Glu Glu Gly Gly Pro Glu

260 265 270

Thr Ser Val Cys Ser Gly Ser Ala Phe Leu Lys Ala Trp Val Tyr Arg

275 280 285

Pro Gly Glu Asp Thr Glu Glu Glu Glu Asp Ser Asp Leu Asp Ser Ala

290 295 300

Glu Glu Asp Thr Ala His Thr Cys Thr Thr Pro His Thr Ser Ala Phe

305 310 315 320

Leu Lys Ala Trp Val Tyr Arg Pro Gly Glu Asp Thr Glu Glu Glu Asp

325 330 335

Asp Gly Asp Trp Asp Ser Ala Glu Glu Asp Thr Ala Gln Ser Cys Thr

340 345 350

Thr Pro His Thr Ser Ala Phe Leu Lys Ala Trp Val Tyr Arg Pro Gly

355 360 365

Glu Asp Thr Glu Glu Glu Asp Asp Ser Glu Asn Val Ala Pro Val Asp

370 375 380

Ser Glu Thr Val Asp Ser Cys Gln Ser Thr Gln His Cys Leu Pro Val

385 390 395 400

Glu Lys Thr Lys Gly Cys Gly Glu Ala Glu Pro Pro Pro Phe Gln Val

405 410 415

Ala Phe Tyr Leu Pro Gly Gln Lys Pro Ala Pro Pro Trp Ala Ala Pro

420 425 430

Lys Leu Pro Leu Arg Leu Gln Lys Arg Leu Arg Ser Phe Lys Ala Pro

435 440 445

Ala Arg Asn Gln Asp Pro Glu Ile Pro Leu Lys Gly Arg Lys Val His

450 455 460

Phe Ser Glu Lys Val Thr Val His Phe Leu Ala Val Trp Ala Gly Pro

465 470 475 480

Ala Gln Ala Ala Arg Arg Gly Pro Trp Glu Gln Phe Ala Arg Asp Arg

485 490 495

Ser Arg Phe Ala Arg Arg Ile Ala Gln Ala Glu Glu Gln Leu Gly Pro

500 505 510

Tyr Leu Thr Pro Ala Phe Arg Ala Arg Ala Trp Thr Arg Leu Arg Asn

515 520 525

Leu Pro Leu Pro Leu Ser Ser Ser Ser Leu Pro Leu Pro Glu Pro Cys

530 535 540

Ser Ser Thr Glu Ala Thr Pro Leu Ser Gln Asp Val Thr Thr Pro Ser

545 550 555 560

Pro Leu Pro Ser Glu Ile Pro Pro Pro Ser Leu Asp Leu Gly Gly Arg

565 570 575

Arg Gly

<210>50

<211>357

<212>PRT

<213>Rattus sp.

<400>50

Met Ala Glu Leu Gln Glu Val Gln Ile Thr Glu Glu Lys Pro Leu Leu

1 5 10 15

Pro Gly Gln Thr Pro Glu Ala Ala Lys Thr His Ser Val Glu Thr Pro

20 25 30

Tyr Gly Ser Val Thr Phe Thr Val Tyr Gly Thr Pro Lys Pro Lys Arg

35 40 45

Pro Ala Ile Phe Thr Tyr His Asp Val Gly Leu Asn Tyr Lys Ser Cys

50 55 60

Phe Gln Pro Leu Phe Gln Phe Gly Asp Met Gln Glu Ile Ile Gln Asn

65 70 75 80

Phe Val Arg Val His Val Asp Ala Pro Gly Met Glu Glu Gly Ala Pro

85 90 95

Val Phe Pro Leu Gly Tyr Gln Tyr Pro Ser Gln Asp Gln Leu Ala Asp

100 105 110

Met Ile Pro Cys Ile Leu Gln Tyr Leu Asn Phe Ser Thr Ile Ile Gly

115 120 125

Val Gly Val Gly Ala Gly Ala Tyr Ile Leu Ser Arg Tyr Ala Leu Asn

130 135 140

His Pro Asp Thr Val Glu Gly Leu Val Leu Ile Asn Ile Asp Pro Asn

145 150 155 160

Ala Lys Gly Trp Met Asp Trp Ala Ala His Lys Leu Thr Gly Leu Thr

165 170 175

Ser Ser Ile Pro Glu Met Ile Leu Gly His Leu Phe Ser Gln Glu Glu

180 185 190

Leu Ser Gly Asn Ser Glu Leu Ile Gln Lys Tyr Arg Ser Leu Ile Thr

195 200 205

His Ala Pro Asn Leu Glu Asn Ile Glu Leu Tyr Trp Asn Ser Tyr Asn

210 215 220

Asn Arg Arg Asp Leu Asn Phe Glu Arg Gly Gly Glu Met Thr Leu Lys

225 230 235 240

Cys Pro Val Met Leu Val Val Gly Asp Gln Ala Pro His Glu Asp Ala

245 250 255

Val Val Glu Cys Asn Ser Lys Leu Asp Pro Thr Gln Thr Ser Phe Leu

260 265 270

Lys Met Ala Asp Ser Gly Gly Gln Pro Gln Leu Thr Gln Pro Gly Lys

275 280 285

Leu Thr Glu Ala Phe Lys Tyr Phe Val Gln Gly Met Gly Tyr Met Ala

290 295 300

Ser Ser Cys Met Thr Arg Leu Ser Arg Ser Arg Thr Ala Ser Leu Thr

305 310 315 320

Ser Ala Ala Ser Ile Asp Gly Ser Arg Ser Arg Ser Arg Thr Leu Ser

325 330 335

Gln Ser Ser Glu Ser Gly Thr Leu Pro Ser Gly Pro Pro Gly His Thr

340 345 350

Met Glu Val Ser Cys

355

<210>51

<211>152

<212>PRT

<213>Rattus sp.

<400>51

Met Ala Asn Ser Glu Arg Thr Phe Ile Ala Ile Lys Pro Asp Gly Val

1 5 10 15

Gln Arg Gly Leu Val Gly Glu Ile Ile Lys Arg Phe Glu Gln Lys Gly

20 25 30

Phe Arg Leu Val Gly Leu Lys Phe Ile Gln Ala Ser Glu Asp Leu Leu

35 40 45

Lys Glu His Tyr Ile Asp Leu Lys Asp Arg Pro Phe Phe Ser Gly Leu

50 55 60

Val Lys Tyr Met His Ser Gly Pro Val Val Ala Met Val Trp Glu Gly

65 70 75 80

Leu Asn Val Val Lys Thr Gly Arg Val Met Leu Gly Glu Thr Asn Pro

85 90 95

Ala Asp Ser Lys Pro Gly Thr Ile Arg Gly Asp Phe Cys Ile Gln Val

100 105 110

Gly Arg Asn Ile Ile His Gly Ser Asp Ser Val Glu Ser Ala Glu Lys

115 120 125

Glu Ile Ser Leu Trp Phe Gln Pro Glu Glu Leu Val Asp Tyr Lys Ser

130 135 140

Cys Ala Gln Asn Trp Ile Tyr Glu

145 150

<210>52

<211>636

<212>PRT

<213>Rattus sp.

<400>52

Met Ser Glu Arg Lys Glu Gly Arg Gly Lys Gly Lys Gly Lys Lys Lys

1 5 10 15

Asp Arg Gly Ser Arg Gly Lys Pro Gly Pro Ala Glu Gly Asp Pro Ser

20 25 30

Pro Ala Leu Pro Pro Arg Leu Lys Glu Met Lys Ser Gln Glu Ser Ala

35 40 45

Ala Gly Ser Lys Leu Val Leu Arg Cys Glu Thr Ser Ser Glu Tyr Ser

50 55 60

Ser Leu Arg Phe Lys Trp Phe Lys Asn Gly Asn Glu Leu Asn Arg Lys

65 70 75 80

Asn Lys Pro Glu Asn Ile Lys Ile Gln Lys Lys Pro Gly Lys Ser Glu

85 90 95

Leu Arg Ile Asn Lys Ala Ser Leu Ala Asp Ser Gly Glu Tyr Met Cys

100 105 110

Lys Val Ile Ser Lys Leu Gly Asn Asp Ser Ala Ser Ala Asn Ile Thr

115 120 125

Ile Val Glu Ser Asn Glu Phe Ile Thr Gly Met Pro Ala Ser Thr Glu

130 135 140

Thr Ala Tyr Val Ser Ser Glu Ser Pro Ile Arg Ile Ser Val Ser Thr

145 150 155 160

Glu Gly Ala Asn Thr Ser Ser Ser Thr Ser Thr Ser Thr Thr Gly Thr

165 170 175

Ser His Leu Ile Lys Cys Ala Glu Lys Glu Lys Thr Phe Cys Val Asn

180 185 190

Gly Gly Glu Cys Phe Thr Val Lys Asp Leu Ser Asn Pro Ser Arg Tyr

195 200 205

Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asn Tyr

210 215 220

Val Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln Lys Arg Val

225 230 235 240

Leu Thr Ile Thr Gly Ile Cys Ile Ala Leu Leu Val Val Gly Ile Met

245 250 255

Cys Val Val Ala Tyr Cys Lys Thr Lys Lys Gln Arg Gln Lys Leu His

260 265 270

Asp Arg Leu Arg Gln Ser Leu Arg Ser Glu Arg Ser Asn Leu Val Asn

275 280 285

Ile Ala Asn Gly Pro His His Pro Asn Pro Pro Pro Glu Asn Val Gln

290 295 300

Leu Val Asn Gln Tyr Val Ser Lys Asn Val Ile Ser Ser Glu His Ile

305 310 315 320

Val Glu Arg Glu Val Glu Thr Ser Phe Ser Thr Ser His Tyr Thr Ser

325 330 335

Thr Ala His His Ser Thr Thr Val Thr Gln Thr Pro Ser His Ser Trp

340 345 350

Ser Asn Gly His Thr Glu Ser Val Ile Ser Glu Ser Asn Ser Val Ile

355 360 365

Met Met Ser Ser Val Glu Asn Ser Arg His Ser Ser Pro Ala Gly Gly

370 375 380

Pro Arg Gly Arg Leu His Gly Leu Gly Gly Pro Arg Asp Asn Ser Phe

385 390 395 400

Leu Arg His Ala Arg Glu Thr Pro Asp Ser Tyr Arg Asp Ser Pro His

405 410 415

Ser Glu Arg Tyr Val Ser Ala Met Thr Thr Pro Ala Arg Met Ser Pro

420 425 430

Val Asp Phe His Thr Pro Ser Ser Pro Lys Ser Pro Pro Ser Glu Met

435 440 445

Ser Pro Pro Val Ser Ser Met Thr Val Ser Met Pro Ser Val Ala Val

450 455 460

Ser Pro Phe Val Glu Glu Glu Arg Pro Leu Leu Leu Val Thr Pro Pro

465 470 475 480

Arg Leu Arg Glu Lys Lys Tyr Asp His His Pro Gln Gln Leu Asn Ser

485 490 495

Phe His His Asn Pro Ala His Gln Ser Thr Ser Leu Pro Pro Ser Pro

500 505 510

Leu Arg Ile Val Glu Asp Glu Glu Tyr Glu Thr Thr Gln Glu Tyr Glu

515 520 525

Ser Val Gln Glu Pro Val Lys Lys Val Thr Asn Ser Arg Arg Ala Lys

530 535 540

Arg Thr Lys Pro Asn Gly His Ile Ala Asn Arg Leu Glu Met Asp Ser

545 550 555 560

Asn Thr Ser Ser Val Ser Ser Asn Ser Glu Ser Glu Thr Glu Asp Glu

565 570 575

Arg Val Gly Glu Asp Thr Pro Phe Leu Gly Ile Gln Asn Pro Leu Ala

580 585 590

Ala Ser Leu Glu Val Ala Pro Ala Phe Arg Leu Ala Glu Ser Arg Thr

595 600 605

Asn Pro Ala Gly Arg Phe Ser Thr Gln Glu Glu Leu Gln Ala Arg Leu

610 615 620

Ser Ser Val Ile Ala Asn Gln Asp Pro Ile Ala Val

625 630 635

<210>53

<211>364

<212>PRT

<213>Rattus sp.

<400>53

Met Ala Phe Asp Asp Lys Met Lys Pro Val Asn Gly Gln Pro Asp Gln

1 5 10 15

Lys Ser Cys Gly Lys Lys Pro Lys Gly Leu His Leu Leu Ser Ser Thr

20 25 30

Trp Trp Cys Pro Ala Ala Val Thr Leu Ala Ile Leu Cys Leu Val Leu

35 40 45

Ser Val Thr Leu Ile Val Gln Gln Thr Gln Leu Leu Gln Val Ser Asp

50 55 60

Leu Leu Lys Gln Tyr Gln Ala Asn Leu Thr Gln Gln Asp His Ile Leu

65 70 75 80

Glu Gly Gln Met Ser Ala Gln Lys Lys Ala Glu Asn Ala Ser Gln Glu

85 90 95

Ser Lys Arg Glu Leu Lys Glu Gln Ile Asp Thr Leu Thr Trp Lys Leu

100 105 110

Asn Glu Lys Ser Lys Glu Gln Glu Lys Leu Leu Gln Gln Asn Gln Asn

115 120 125

Leu Gln Glu Ala Leu Gln Arg Ala Val Asn Ala Ser Glu Glu Ser Lys

130 135 140

Trp Glu Leu Lys Glu Gln Ile Asp Ile Leu Asn Trp Lys Leu Asn Gly

145 150 155 160

Ile Ser Lys Glu Gln Lys Glu Leu Leu Gln Gln Asn Gln Asn Leu Gln

165 170 175

Glu Ala Leu Gln Lys Ala Glu Lys Tyr Ser Glu Glu Ser Gln Arg Glu

180 185 190

Leu Lys Glu Gln Ile Asp Thr Leu Ser Trp Lys Leu Asn Glu Lys Ser

195 200 205

Lys Glu Gln Glu Glu Leu Leu Gln Gln Asn Gln Asn Leu Gln Glu Ala

210 215 220

Leu Gln Arg Ala Ala Asn Ser Ser Gly Pro Cys Pro Gln Asp Trp Ile

225 230 235 240

Trp His Lys Glu Asn Cys Tyr Leu Phe His Gly Pro Phe Asn Trp Glu

245 250 255

Lys Ser Arg Glu Asn Cys Leu Ser Leu Asp Ala Gln Leu Leu Gln Ile

260 265 270

Ser Thr Thr Asp Asp Leu Asn Phe Val Leu Gln Ala Thr Ser His Ser

275 280 285

Thr Ser Pro Phe Trp Met Gly Leu His Arg Lys Asn Pro Asn His Pro

290 295 300

Trp Leu Trp Glu Asn Gly Ser Pro Leu Ser Phe Gln Phe Phe Arg Thr

305 310 315 320

Arg Gly Val Ser Leu Gln Met Tyr Ser Ser Gly Thr Cys Ala Tyr Ile

325 330 335

Gln Gly Gly Val Val Phe Ala Glu Asn Cys Ile Leu Thr Ala Phe Ser

340 345 350

Ile Cys Gln Lys Lys Ala Asn Leu Leu Leu Thr Gln

355 360

<210>54

<211>350

<212>PRT

<213>Rattus sp.

<400>54

Met Ser His Gln Thr Gly Ile Gln Ala Ser Glu Asp Val Lys Glu Ile

1 5 10 15

Phe Ala Arg Ala Arg Asn Gly Lys Tyr Arg Leu Leu Lys Ile Ser Ile

20 25 30

Glu Asn Glu Gln Leu Val Val Gly Ser Cys Ser Pro Pro Ser Asp Ser

35 40 45

Trp Glu Gln Asp Tyr Asp Pro Phe Val Leu Pro Leu Leu Glu Asp Lys

50 55 60

Gln Pro Cys Tyr Val Leu Phe Arg Leu Asp Ser Gln Asn Ala Gln Gly

65 70 75 80

Tyr Glu Trp Ile Phe Ile Ala Trp Ser Pro Asp His Ser His Val Arg

85 90 95

Gln Lys Met Leu Tyr Ala Ala Thr Arg Ala Thr Leu Lys Lys Glu Phe

100 105 110

Gly Gly Gly His Ile Lys Asp Glu Val Phe Gly Thr Val Lys Glu Asp

115 120 125

Val Ser Leu His Gly Tyr Arg Lys Tyr Leu Leu Ser Gln Ser Ser Pro

130 135 140

Ala Pro Leu Thr Ala Ala Glu Glu Glu Leu Arg Gln Ile Lys Ile Ser

145 150 155 160

Glu Val Gln Thr Asp Val Ser Val Asp Thr Lys His Gln Thr Leu Gln

165 170 175

Gly Val Ala Phe Pro Ile Ser Arg Asp Ala Phe Gln Ala Leu Glu Lys

180 185 190

Leu Ser Lys Arg Gln Leu Asn Tyr Val Gln Leu Glu Ile Asp Ile Lys

195 200 205

Asn Glu Thr Ile Ile Leu Ala Asn Thr Glu Asn Thr Glu Leu Lys Asp

210 215 220

Leu Pro Lys Arg Ile Pro Lys Asp Ser Ala Arg Tyr His Phe Phe Leu

225 230 235 240

Tyr Lys His Ser His Glu Gly Asp Tyr Leu Glu Ser Ile Val Phe Ile

245 250 255

Tyr Ser Met Pro Gly Tyr Thr Cys Ser Ile Arg Glu Arg Met Leu Tyr

260 265 270

Ser Ser Cys Lys Ser Pro Leu Leu Asp Ile Val Glu Arg Gln Leu Gln

275 280 285

Met Asp Val Ile Arg Lys Ile Glu Ile Asp Asn Gly Asp Glu Leu Thr

290 295 300

Ala Asp Phe Leu Tyr Asp Glu Val His Pro Lys Gln His Ala His Lys

305 310 315 320

Gln Ser Phe Ala Lys Pro Lys Gly Pro Ala Gly Lys Arg Gly Ile Arg

325 330 335

Arg Leu Ile Arg Gly Pro Ala Glu Ala Glu Ala Thr Thr Asp

340 345 350

<210>55

<211>300

<212>PRT

<213>Rattus sp.

<400>55

Met Ser Leu Tyr Pro Ser Leu Glu Asp Leu Lys Val Asp Lys Val Ile

1 5 10 15

Gln Ala Gln Thr Ala Ser Ser Ala Asn Pro Ala Ser Gln Ala Phe Phe

20 25 30

Leu Asn Val Val Asp Ser Ala Ala Phe Pro Pro Gly Gly Asn Leu Tyr

35 40 45

Pro Lys Leu Tyr Pro Glu Leu Ser Gln Tyr Met Gly Leu Ser Leu Ser

50 55 60

Glu Ala Glu Ile Cys Glu Asn Met Pro Val Val Ser Gly Ala Pro Thr

65 70 75 80

Gln Gly Gln Leu Val Ala Arg Pro Ser Ser Val Asn Tyr Met Val Ala

85 90 95

Pro Val Thr Gly Asn Asp Ala Gly Ile Arg Arg Ala Glu Ile Lys Gln

100 105 110

Gly Ile Arg Glu Val Ile Leu Cys Lys Asp Gln Asp Gly Lys Ile Gly

115 120 125

Leu Arg Leu Lys Ser Val Asp Asn Gly Ile Phe Val Gln Leu Val Gln

130 135 140

Ala Asn Ser Pro Ala Ser Leu Val Gly Leu Arg Phe Gly Asp Gln Val

145 150 155 160

Leu Gln Ile Asn Gly Glu Asn Cys Ala Gly Trp Ser Ser Asp Lys Ala

165 170 175

His Lys Val Leu Lys Gln Ala Phe Gly Glu Lys Ile Thr Met Thr Ile

180 185 190

Arg Asp Arg Pro Phe Glu Arg Thr Val Thr Met His Lys Asp Ser Ser

195 200 205

Gly His Val Gly Phe Ile Phe Lys Ser Gly Lys Ile Thr Ser Ile Val

210 215 220

Lys Asp Ser Ser Ala Ala Arg Asn Gly Leu Leu Thr Asp His His Ile

225 230 235 240

Cys Glu Ile Asn Gly Gln Asn Val Ile Gly Leu Lys Asp Ala Gln Ile

245 250 255

Ala Asp Ile Leu Ser Thr Ala Gly Thr Val Val Thr Ile Thr Ile Met

260 265 270

Pro Ala Phe Ile Phe Glu His Ile Ile Lys Arg Met Ala Pro Ser Ile

275 280 285

Met Lys Ser Leu Met Asp His Thr Ile Pro Glu Val

290 295 300

<210>56

<211>79

<212>PRT

<213>Rattus sp.

<400>56

Met Lys Val Ala Ile Ile Phe Leu Leu Ser Ala Leu Ala Leu Leu Ser

1 5 10 15

Leu Ala Gly Asn Pro Pro Ala Glu Val Asn Gly Lys Thr Pro Asn Cys

20 25 30

Pro Lys Gln Ile Met Gly Cys Pro Arg Ile Tyr Asp Pro Val Cys Gly

35 40 45

Thr Asn Gly Ile Thr Tyr Pro Ser Glu Cys Ser Leu Cys Phe Glu Asn

50 55 60

Arg Lys Phe Gly Thr Ser Ile His Ile Gln Arg Arg Gly Thr Cys

65 70 75

<210>57

<211>246

<212>PRT

<213>Rattus sp.

<400>57

Met Gly Asp Arg Glu Gln Leu Leu Gln Arg Ala Arg Leu Ala Glu Gln

1 5 10 15

Ala Glu Arg Tyr Asp Asp Met Ala Ser Ala Met Lys Ala Val Thr Glu

20 25 30

Leu Asn Glu Pro Leu Ser Asn Glu Asp Arg Asn Leu Leu Ser Val Ala

35 40 45

Tyr Lys Asn Val Val Gly Ala Arg Arg Ser Ser Trp Arg Val Ile Ser

50 55 60

Ser Ile Glu Gln Lys Thr Met Ala Asp Gly Asn Glu Lys Lys Leu Glu

65 70 75 80

Lys Val Lys Ala Tyr Arg Glu Lys Ile Glu Lys Glu Leu Glu Thr Val

85 90 95

Cys Asn Asp Val Leu Ala Leu Leu Asp Lys Phe Leu Ile Lys Asn Cys

100 105 110

Asn Asp Phe Gln Tyr Glu Ser Lys Val Phe Tyr Leu Lys Met Lys Gly

115 120 125

Asp Tyr Tyr Arg Tyr Leu Ala Glu Val Ala Ser Gly Glu Lys Lys Asn

130 135 140

Ser Val Val Glu Ala Ser Glu Ala Ala Tyr Lys Glu Ala Phe Glu Ile

145 150 155 160

Ser Lys Glu His Met Gln Pro Thr His Pro Ile Arg Leu Gly Leu Ala

165 170 175

Leu Asn Phe Ser Val Phe Tyr Tyr Glu Ile Gln Asn Ala Pro Glu Gln

180 185 190

Ala Cys Leu Leu Ala Lys Gln Ala Phe Asp Asp Ala Ile Ala Glu Leu

195 200 205

Asp Thr Leu Asn Glu Asp Ser Tyr Lys Asp Ser Thr Leu Ile Met Gln

210 215 220

Leu Leu Arg Asp Asn Leu Thr Leu Trp Thr Ser Asp Gln Gln Asp Glu

225 230 235 240

Glu Ala Gly Glu Gly Asn

245

<210>58

<211>95

<212>PRT

<213>Rattus sp.

<400>58

Met Pro Ser Gln Met Glu His Ala Met Glu Thr Met Met Leu Thr Phe

1 5 10 15

His Arg Phe Ala Gly Glu Lys Asn Tyr Leu Thr Lys Glu Asp Leu Arg

20 25 30

Val Leu Met Glu Arg Glu Phe Pro Gly Phe Leu Glu Asn Gln Lys Asp

35 40 45

Pro Leu Ala Val Asp Lys Ile Met Lys Asp Leu Asp Gln Cys Arg Asp

50 55 60

Gly Lys Val Gly Phe Gln Ser Phe Leu Ser Leu Val Ala Gly Leu Ile

65 70 75 80

Ile Ala Cys Asn Asp Tyr Phe Val Val His Met Lys Gln Lys Lys

85 90 95

<210>59

<211>158

<212>PRT

<213>Rattus sp.

<400>59

Met Ser His Gly Lys Arg Thr Asp Met Leu Pro Glu Ile Ala Ala Ala

1 5 10 15

Val Gly Phe Leu Thr Ser Leu Leu Arg Thr Arg Gly Cys Val Ser Glu

20 25 30

Gln Arg Leu Lys Val Phe Ser Arg Ala Leu Gln Asp Ala Leu Thr Asp

35 40 45

His Tyr Lys His His Trp Phe Pro Glu Lys Pro Ser Lys Gly Ser Gly

50 55 60

Tyr Arg Cys Ile Arg Ile Asn His Lys Met Asp Pro Ile Ile Ser Lys

65 70 75 80

Val Ala Ser Gln Ile Gly Leu Ser Gln Pro Gln Leu His Gln Leu Leu

85 90 95

Pro Ser Glu Leu Thr Leu Trp Val Asp Pro Tyr Glu Val Ser Tyr Arg

100 105 110

Ile Gly Glu Asp Gly Ser Ile Cys Val Leu Tyr Glu Glu Ala Pro Val

115 120 125

Ala Thr Ser Tyr Gly Leu Leu Thr Cys Lys Asn Gln Met Met Leu Gly

130 135 140

Arg Ser Ser Pro Ser Lys Asn Tyr Val Met Thr Val Ser Ser

145 150 155

<210>60

<211>875

<212>PRT

<213>Rattus sp.

<400>60

Met Lys Ser Thr Asp Ile Val Leu Lys Ala Asn Gly Leu Leu Leu Asp

1 5 10 15

Leu Lys Gln Gly Lys Ser Leu Thr Leu Pro Val Asn Asp Asn Asp Glu

20 25 30

Arg His Lys Ile Gln Phe Glu Arg Cys Gln Gly Ser Ser Gln Glu Gln

35 40 45

Leu Thr Asn Arg Gly Arg Met Ile Arg Val Ser Asp Lys Leu Ile Ala

50 55 60

Phe Lys Arg Arg Val Lys Cys Val Arg Met Thr Pro Pro Arg Met Ile

65 70 75 80

Ser Ser Leu Thr Thr Arg Leu Glu Leu Thr Val Lys Tyr Pro Val Gly

85 90 95

Ser Asn Arg Thr Lys Gly Glu Arg Met Ala Leu Arg Phe Phe Lys Ala

100 105 110

Arg Val Val Ala Glu Lys Ser Val Arg Arg Thr Leu Pro Cys Ser Gln

115 120 125

Glu His Val Pro Ala Arg Glu Gln Gln Glu Cys Gly Glu Ile Pro Val

130 135 140

Pro Val Lys Phe Lys Ser Gln Trp Val Val Phe Gln Gly Cys Cys Gly

145 150 155 160

Val Arg Leu His Cys Ala Gly Thr Ala Asn Gly Arg Lys Gly Ser Ile

165 170 175

Arg Arg Gly Thr Gly Arg Leu Gly Cys Asp Gln Gln Lys Ser Thr Asn

180 185 190

Val Val Tyr Gln Ala His His Val Ser Arg Asn Lys Arg Gly Gln Val

195 200 205

Val Gly Thr Arg Gly Gly Phe Arg Gly Cys Leu Ser Gly Ala Gly Lys

210 215 220

Thr Thr Ile Ser Phe Ala Leu Glu Glu Tyr Leu Val Ser His Ala Ile

225 230 235 240

Pro Cys Tyr Ser Leu Asp Gly Asp Asn Val Arg His Gly Leu Asn Lys

245 250 255

Asn Leu Gly Phe Ser Ala Gly Asp Arg Glu Glu Asn Ile Arg Arg Ile

260 265 270

Ala Glu Val Ala Lys Leu Phe Ala Asp Ala Gly Leu Val Cys Ile Thr

275 280 285

Ser Phe Ile Ser Pro Phe Ala Lys Gly Pro Leu Ile Ser Ser Ile Gly

290 295 300

Tyr Val Lys Arg Val Ala Ser Val Pro Glu Ala Ser Ala Pro Val Asp

305 310 315 320

Arg Lys Leu Leu Trp Asp Arg Glu Asn Ala Arg Lys Ile His Glu Ser

325 330 335

Ala Gly Leu Pro Phe Phe Glu Ile Phe Val Asp Ala Pro Leu Asn Ile

340 345 350

Cys Glu Ser Arg Asp Val Lys Gly Leu Tyr Lys Arg Ala Arg Ala Gly

355 360 365

Glu Ile Lys Gly Phe Thr Gly Ile Asp Ser Asn Tyr Glu Lys Pro Glu

370 375 380

Thr Pro Glu Cys Val Leu Lys Thr Asn Leu Ser Ser Val Ser Asp Cys

385 390 395 400

Val Gln Gln Val Val Glu Leu Leu Gln Glu Gln Ser Ile Val Pro His

405 410 415

Thr Thr Ile Lys Gly Ile His Glu Leu Phe Val Pro Glu Asn Lys Ile

420 425 430

Asp Gln Ile Arg Ala Glu Leu Glu Thr Leu Pro Ser Leu Pro Ile Thr

435 440 445

Lys Leu Asp Leu Gln Trp Val Gln Ile Leu Ser Glu Gly Trp Ala Thr

450 455 460

Pro Leu Lys Gly Phe Met Arg Glu Lys Glu Tyr Leu Gln Thr Leu His

465 470 475 480

Phe Asp Thr Leu Leu Asp Asp Gly Val Ile Asn Met Ser Ile Pro Ile

485 490 495

Val Leu Pro Val Ser Gly Asp Asp Lys Ala Arg Leu Glu Gly Cys Ser

500 505 510

Lys Phe Ala Leu Met Tyr Glu Gly Arg Arg Val Ala Leu Leu Gln Asp

515 520 525

Pro Glu Phe Tyr Glu His Arg Lys Glu Glu Arg Cys Ser Arg Val Trp

530 535 540

Gly Thr Ala Ser Ala Lys His Pro His Ile Lys Ala Asp Ser Cys Ser

545 550 555 560

Met Pro Tyr Val Ser Thr Gly Ile Val Pro Leu Val Asp Ile Arg Ile

565 570 575

Ala Met Asn Thr Gly Val Gln Ile Ser Leu Gln Asp Met Val Met Glu

580 585 590

Gly Gly Asp Trp Leu Val Gly Gly Asp Leu Gln Val Leu Glu Arg Ile

595 600 605

Arg Trp Asn Asp Gly Leu Asp Gln Tyr Arg Leu Thr Pro Leu Glu Leu

6l0 615 620

Lys Gln Lys Cys Lys Asp Met Asp Ala Gly Ser His Lys Gly Glu Pro

625 630 635 640

Ala Ala Gly Thr Arg Glu Gln Gly Gln Ala Ile Leu Leu Thr Pro Asn

645 650 655

Leu Gly Ser Pro Phe Leu Asp Ala Val Phe Ala Phe Gln Leu Arg Asn

660 665 670

Pro Val His Asn Gly His Ala Leu Leu Met Gln Asp Thr Arg Arg Arg

675 680 685

Leu Leu Glu Arg Gly Tyr Lys His Pro Val Leu Leu Leu His Pro Leu

690 695 700

Gly Gly Trp Thr Lys Asp Asp Asp Val Pro Leu Asp Trp Arg Met Lys

705 710 715 720

Gln His Ala Ala Val Leu Glu Glu Gly Ile Leu Asp Pro Lys Ser Thr

725 730 735

Ile Val Ala Ile Phe Pro Ser Pro Met Leu Tyr Ala Gly Pro Thr Glu

740 745 750

Val Gln Trp His Cys Arg Cys Arg Met Ile Ala Gly Ala Asn Phe Tyr

755 760 765

Ile Val Gly Arg Asp Pro Ala Gly Met Pro His Pro Glu Thr Lys Lys

770 775 780

Asp Leu Tyr Glu Pro Thr His Gly Gly Lys Val Leu Ser Met Ala Pro

785 790 795 800

Gly Leu Thr Ser Val Glu Ile Ile Pro Phe Arg Val Ala Ala Tyr Asn

805 810 815

Lys Ile Lys Lys Ala Met Asp Phe Tyr Asp Pro Ala Arg His Asp Glu

820 825 830

Phe Asp Phe Ile Ser Gly Thr Arg Met Arg Lys Leu Ala Arg Glu Gly

835 840 845

Glu Asp Pro Pro Asp Gly Phe Met Ala Pro Lys Ala Trp Lys Val Leu

850 855 860

Thr Asp Tyr Tyr Arg Ser Leu Glu Lys Ile Asn

865 870 875

<210>61

<211>142

<212>PRT

<213>Rattus sp.

<400>61

Met Ala Ala Ala Ala Glu Gly Val Pro Ala Thr Arg Arg Glu Glu Pro

1 5 10 15

Pro Arg Asp Asp Ala Ala Val Glu Thr Ala Glu Glu Ala Lys Glu Pro

20 25 30

Ala Glu Ala Asp Ile Asn Glu Leu Cys Arg Asp Met Phe Ser Lys Met

35 40 45

Ala Thr Tyr Leu Thr Gly Glu Leu Thr Ala Thr Ser Glu Asp Tyr Lys

50 55 60

Leu Leu Glu Asn Met Asn Lys Leu Thr Ser Leu Lys Tyr Leu Glu Met

65 70 75 80

Lys Asp Ile Ala Ile Asn Ile Ser Arg Asn Leu Lys Asp Leu Asn Gln

85 90 95

Lys Tyr Ala Gly Leu Gln Pro Tyr Leu Asp Gln Ile Asn Val Ile Glu

100 105 110

Glu Gln Val Ala Ala Leu Glu Gln Ala Ala Tyr Lys Leu Asp Ala Tyr

115 120 125

Ser Lys Lys Leu Glu Ala Lys Tyr Lys Lys Leu Glu Lys Arg

130 135 140

<210>62

<211>351

<212>PRT

<213>Rattus sp.

<400>62

Met Pro Ser Gly Leu Pro Cys Pro Ser Leu Asp Arg Arg Gly Ala Arg

1 5 10 15

Arg Val Ala Thr Glu Thr Pro Asp Arg Ser Gly Gly Ala Pro Gly Ala

20 25 30

Leu Ser Ala Pro Gly Gly Ser Gly Gly Val Ser Cys Ser Arg Ala Pro

35 40 45

Trp Arg Pro Gly Ala Ala Leu Val Gly Leu Pro Ser Arg Val Pro Gly

50 55 60

Gly Ala Lys Gly Lys Met Leu Arg Arg Asn Leu Asp Asp Arg Asp Ala

65 70 75 80

Gln Thr Lys Gln Leu Gln Asp Ala Val Thr Asn Val Glu Lys His Phe

85 90 95

Gly Glu Leu Cys Gln Ile Phe Ala Ala Tyr Val Arg Lys Thr Ala Arg

100 105 110

Leu Arg Asp Lys Ala Asp Leu Leu Val Asn Glu Ile Asn Leu Tyr Ala

115 120 125

Ser Thr Glu Thr Pro Asn Leu Lys Gln Gly Leu Lys Asp Phe Ala Asp

130 135 140

Glu Phe Ala Lys Leu Gln Asp Tyr Arg Gln Ala Glu Val Glu Arg Leu

145 150 155 160

Glu Ala Lys Val Val Glu Pro Leu Lys Ala Tyr Gly Thr Ile Val Lys

165 170 175

Met Lys Arg Asp Asp Leu Lys Ala Thr Leu Thr Ala Arg Asn Arg Glu

180 185 190

Ala Lys Gln Leu Ser Gln Leu Glu Arg Thr Arg Gln Arg Asn Pro Ser

195 200 205

Asp Arg His Ala Glu Thr Glu Leu Gln Arg Ala Thr Ile Asp Ala Thr

210 215 220

Arg Thr Thr Arg His Leu Glu Glu Thr Ile Asp Asn Phe Glu Lys Gln

225 230 235 240

Lys Ile Lys Asp Ile Lys Asn Ile Leu Ser Glu Phe Ile Thr Ile Glu

245 250 255

Met Leu Phe His Gly Lys Ala Leu Glu Val Leu Thr Ala Ala Tyr Gln

260 265 270

Asn Ile Gln Lys Ile Asp Glu Asp Glu Asp Leu Glu Val Phe Arg Asn

275 280 285

Ser Leu Tyr Leu Ser Asp Tyr Pro Ser Arg Leu Asp Ile Val Arg Ala

290 295 300

Asn Ser Lys Ser Pro Leu Gln Arg Pro Leu Ser Thr Lys Cys Thr Ser

305 310 315 320

Gly Thr Gly Gln Val Ala Thr Cys Arg Thr Lys Lys Asp Gln His Val

325 330 335

Glu Asp Glu Asp Asp Glu Glu Leu Asp Val Thr Glu Asp Glu Asn

340 345 350

<210>63

<211>676

<212>PRT

<213>Rattus sp.

<400>63

Met Asn Leu Phe Gly Phe Ala Ser Cys Gln Leu Ile Leu Val Pro Ser

1 5 10 15

Gln Gly Arg Thr Ala Gly Gly His Asp His Ser Arg Ser Asn Leu Asp

20 25 30

Glu Lys Asp Ser Gly Ser Ala Gly Ser Gly Phe Ser Pro Ser Pro Thr

35 40 45

Ser Leu Val Pro Thr Gly Trp Phe Arg Ser Pro Asn Thr Val Leu Leu

50 55 60

Leu Ser Asn Val Phe His Ser Pro Arg Asp Pro Ile Met Thr Val Val

65 70 75 80

Leu Leu Leu Pro Leu Arg Phe Glu Cys Lys His Asn Arg Ala Ala Arg

85 90 95

Tyr Arg Asp Pro Ser Pro Leu Pro Pro Arg Ser Ser Thr Ala Arg Pro

100 105 110

Leu Ser Pro Ala Gln Gly Pro Pro Pro Ser Pro Ile Gly Ser Gly Gly

115 120 125

Gly Ala Gly Arg Ala Arg Ser Asp Ala Arg Met Ala Leu Gly Phe Arg

130 135 140

Pro Arg Arg Leu Ala Gly Ser Arg Gly Asp Gly Leu Leu Ala Pro Gly

145 150 155 160

His Asp Ala Leu Ile His Gln Ala Val Cys Arg Arg Ala Glu Thr Asp

165 170 175

Thr Pro Gly Thr Ser Pro Thr Thr Val Leu Leu Leu Arg Ala Ser Arg

180 185 190

Pro Met Cys Asn Thr Asn Met Ser Val Ser Thr Glu Gly Ala Ala Gly

195 200 205

Thr Ser Gln Ile Pro Ala Ser Glu Gln Glu Thr Leu Val Arg Pro Lys

210 215 220

Pro Leu Leu Leu Lys Leu Leu Lys Ser Val Gly Ala Gln Lys Asp Ile

225 230 235 240

Tyr Thr Met Lys Glu Ile Ile Phe Tyr Ile Gly Gln Tyr Ile Met Thr

245 250 255

Lys Arg Leu Tyr Asp Glu Lys Gln Gln His Ile Val Tyr Cys Ser Asn

260 265 270

Asp Leu Leu Gly Asp Val Phe Gly Val Pro Ser Phe Ser Val Lys Glu

275 280 285

His Arg Lys Ile Tyr Ala Met Ile Tyr Arg Asn Leu Val Val Val Ser

290 295 300

Gln Gln Asp Ser Gly Thr Ser Pro Ser Glu Ser Arg Cys Gln Pro Glu

305 310 315 320

Gly Gly Ser Asp Leu Lys Asp Pro Val Gln Ala Ser Gln Glu Glu Lys

325 330 335

Pro Ser Ser Ser Asp Val Val Ser Arg Pro Ser Thr Ser Ser Arg Arg

340 345 350

Arg Ala Ile Ser Glu Thr Glu Glu Asn Thr Asp Glu Leu Pro Gly Glu

355 360 365

Arg Gln Arg Lys Arg His Arg Ala Leu Ser Phe Asp Glu Ser Leu Gly

370 375 380

Leu Cys Val Leu Arg Glu Ile Cys Cys Glu Arg Ser Ser Ser Ser Glu

385 390 395 400

Ala Thr Asp Thr Pro Ser His Gln Asp Leu Asp Asp Gly Val Ser Asp

405 410 415

His Ser Ala Asp Cys Leu Asp Gln Asp Ser Val Ser Asp Gln Phe Ser

420 425 430

Val Glu Phe Glu Val Glu Ser Leu Asp Ser Glu Asp Tyr Ser Leu Ser

435 440 445

Asp Glu Gly His Glu Leu Ser Asp Glu Asp Asp Glu Val Tyr Arg Val

450 455 460

Thr Val Tyr Gln Ala Gly Glu Ser Asp Ala Asp Ser Phe Glu Gly Asp

465 470 475 480

Pro Glu Ile Ser Leu Ala Asp Tyr Trp Lys Cys Thr Ser Cys Asn Glu

485 490 495

Met Asn Pro Pro Leu Pro Ser His Cys Asn Arg Cys Trp Thr Leu Arg

500 505 510

Glu Asn Trp Leu Pro Asp Asp Lys Gly Lys Asp Lys Val Glu Ile Ser

515 520 525

Glu Lys Ala Lys Leu Glu Ser Ser Asp Gln Ala Glu Glu Gly Leu Asp

530 535 540

Val Pro Asp Gly Lys Lys Val Thr Glu Asp Asp Ala Lys Glu Ser Ser

545 550 555 560

Ala Glu Asp Ser Glu Glu Lys Val Ala Gln Met Leu Leu Ser Gln Glu

565 570 575

Ser Asp Asp Tyr Ser Gln Pro Ser Thr Ser Ser Ser Ile Val Tyr Ser

580 585 590

Ser Gln Glu Ser Gly Lys Glu Leu Lys Glu Asp Thr Gln Asp Lys Glu

595 600 605

Glu Ser Met Glu Ser Ser Phe Ser Leu Asn Ala Ile Glu Pro Cys Val

610 615 620

Ile Cys Gln Gly Arg Pro Lys Asn Gly Cys Ile Val His Gly Lys Thr

625 630 635 640

Gly His Leu Met Ser Cys Phe Thr Cys Ala Lys Lys Leu Lys Lys Arg

645 650 655

Asn Lys Pro Cys Pro Val Cys Arg Gln Pro Ile Gln Met Ile Val Leu

660 665 670

Thr Tyr Phe Asn

675

<210>64

<211>2511

<212>PRT

<213>人(Homo sapiens)

<400>64

Met Glu Glu Val Val Ile Ala Gly Met Ser Gly Lys Leu Pro Glu Ser

1 5 10 15

Glu Asn Leu Gln Glu Phe Trp Asp Asn Leu Ile Gly Gly Val Asp Met

20 25 30

Val Thr Asp Asp Asp Arg Arg Trp Lys Ala Gly Leu Tyr Gly Leu Pro

35 40 45

Arg Arg Ser Gly Lys Leu Lys Asp Leu Ser Arg Phe Asp Ala Ser Phe

50 55 60

Phe Gly Val His Pro Lys Gln Ala His Thr Met Asp Pro Gln Leu Arg

65 70 75 80

Leu Leu Leu Glu Val Thr Tyr Glu Ala Ile Val Asp Gly Gly Ile Asn

85 90 95

Pro Asp Ser Leu Arg Gly Thr His Thr Gly Val Trp Val Gly Val Ser

100 105 110

Gly Ser Glu Thr Ser Glu Ala Leu Ser Arg Asp Pro Glu Thr Leu Val

115 120 125

GIy Tyr Ser Met Val Gly Cys Gln Arg Ala Met Met Ala Asn Arg Leu

130 135 140

Ser Phe Phe Phe Asp Phe Arg Gly Pro Ser Ile Ala Leu Asp Thr Ala

145 150 155 160

Cys Ser Ser Ser Leu Met Ala Leu Gln Asn Ala Tyr Gln Ala Ile His

165 170 175

Ser Gly Gln Cys Pro Ala Ala Ile Val Gly Gly Ile Asn Val Leu Leu

180 185 190

Lys Pro Asn Thr Ser Val Gln Phe Leu Arg Leu Gly Met Leu Ser Pro

195 200 205

Glu Gly Thr Cys Lys Ala Phe Asp Thr Ala Gly Asn Gly Tyr Cys Arg

210 215 220

Ser Glu Gly Val Val Ala Val Leu Leu Thr Lys Lys Ser Leu Ala Arg

225 230 235 240

Arg Val Tyr Ala Thr Ile Leu Asn Ala Gly Thr Asn Thr Asp Gly Phe

245 250 255

Lys Glu Gln Gly Val Thr Phe Pro Ser Gly Asp Ile Gln Glu Gln Leu

260 265 270

Ile Arg Ser Leu Tyr Gln Ser Ala Gly Val Ala Pro Glu Ser Phe Glu

275 280 285

Tyr Ile Glu Ala His Gly Thr Gly Thr Lys Val Gly Asp Pro Gln Glu

290 295 300

Leu Asn Gly Ile Thr Arg Ala Leu Cys Ala Thr Arg Gln Glu Pro Leu

305 310 315 320

Leu Ile Gly Ser Thr Lys Ser Asn Met Gly His Pro Glu Pro Ala Ser

325 330 335

Gly Leu Ala Ala Leu Ala Lys Val Leu Leu Ser Leu Glu His Gly Leu

340 345 350

Trp Ala Pro Asn Leu His Phe His Ser Pro Asn Pro Glu Ile Pro Ala

355 360 365

Leu Leu Asp Gly Arg Leu Gln Val Val Asp Gln Pro Leu Pro Val Arg

370 375 380

Gly Gly Asn Val Gly Ile Asn Ser Phe Gly Phe Gly Gly Ser Asn Val

385 390 395 400

His Ile Ile Leu Arg Pro Asn Thr Gln Pro Pro Pro Ala Pro Ala Pro

405 410 415

His Ala Thr Leu Pro Arg Leu Leu Arg Ala Ser Gly Arg Thr Pro Glu

420 425 430

Ala Val Gln Lys Leu Leu Glu Gln Gly Leu Arg His Ser Gln Asp Leu

435 440 445

Ala Phe Leu Ser Met Leu Asn Asp Ile Ala Ala Val Pro Ala Thr Ala

450 455 460

Met Pro Phe Arg Gly Tyr Ala Val Leu Gly Gly Glu Arg Gly Gly Pro

465 470 475 480

Glu Val Gln Gln Val Pro Ala Gly Glu Arg Pro Leu Trp Phe Ile Cys

485 490 495

Ser Gly Met Gly Thr Gln Trp Arg Gly Met Gly Leu Ser Leu Met Arg

500 505 510

Leu Asp Arg Phe Arg Asp Ser Ile Leu Arg Ser Asp Glu Ala Val Lys

515 520 525

Pro Phe Gly Leu Lys Val Ser Gln Leu Leu Leu Ser Thr Asp Glu Ser

530 535 540

Thr Phe Asp Asp Ile Val His Ser Phe Val Ser Leu Thr Ala Ile Gln

545 550 555 560

Ile Gly Leu Ile Asp Leu Leu Ser Cys Met Gly Leu Arg Pro Asp Gly

565 570 575

Ile Val Gly His Ser Leu Gly Glu Val Ala Cys Gly Tyr Ala Asp Gly

580 585 590

Cys Leu Ser Gln Glu Glu Ala Val Leu Ala Ala Tyr Trp Arg Gly Gln

595 600 605

Cys Ile Lys Glu Ala His Leu Pro Pro Gly Ala Met Ala Ala Val Gly

610 615 620

Leu Ser Trp Glu Glu Cys Lys Gln Arg Cys Pro Pro Gly Val Val Pro

625 630 635 640

Ala Cys His Asn Ser Lys Asp Thr Val Thr Ile Ser Gly Pro Gln Ala

645 650 655

Pro Val Phe Glu Phe Val Glu Gln Leu Arg Lys Glu Gly Val Phe Ala

660 665 670

Lys Glu Val Arg Thr Gly Gly Met Ala Phe His Ser Tyr Phe Met Glu

675 680 685

Ala Ile Ala Pro Pro Leu Leu Gln Glu Leu Lys Lys Val Ile Arg Glu

690 695 700

Pro Lys Pro Arg Ser Ala Arg Trp Leu Ser Thr Ser Ile Pro Glu Ala

705 710 715 720

Gln Trp His Ser Ser Leu Ala Arg Thr Ser Ser Ala Glu Tyr Asn Val

725 730 735

Asn Asn Leu Val Ser Pro Val Leu Phe Gln Glu Ala Leu Trp His Val

740 745 750

Pro Glu His Ala Val Val Leu Glu Ile Ala Pro His Ala Leu Leu Gln

755 760 765

Ala Val Leu Lys Arg Gly Leu Lys Pro Ser Cys Thr Ile Ile Pro Leu

770 775 780

Met Lys Lys Asp His Arg Asp Asn Leu Glu Phe Phe Leu Ala Gly Ile

785 790 795 800

Gly Arg Leu His Leu Ser Gly Ile Asp Ala Asn Pro Asn Ala Leu Phe

805 810 815

Pro Pro Val Glu Phe Pro Ala Pro Arg Gly Thr Pro Leu Ile Ser Pro

820 825 830

Leu Ile Lys Trp Asp His Ser Leu Ala Trp Asp Val Pro Ala Ala Glu

835 840 845

Asp Phe Pro Asn Gly Ser Gly Ser Pro Ser Ala Ala Ile Tyr Asn Ile

850 855 860

Asp Thr Ser Ser Glu Ser Pro Asp His Tyr Leu Val Asp His Thr Leu

865 870 875 880

Asp Gly Arg Val Leu Phe Pro Ala Thr Gly Tyr Leu Ser Ile Val Trp

885 890 895

Lys Thr Leu Ala Arg Ala Leu Gly Leu Gly Val Glu Gln Leu Pro Val

900 905 910

Val Phe Glu Asp Val Val Leu His Gln Ala Thr Ile Leu Pro Lys Thr

915 920 925

Gly Thr Val Ser Leu Glu Val Arg Leu Leu Glu Ala Ser Arg Ala Phe

930 935 940

Glu Val Ser Glu Asn Gly Asn Leu Val Val Ser Gly Lys Val Tyr Gln

945 950 955 960

Trp Asp Asp Pro Asp Pro Arg Leu Phe Asp His Pro Glu Ser Pro Thr

965 970 975

Pro Asn Pro Thr Glu Pro Leu Phe Leu Ala Gln Ala Glu Val Tyr Lys

980 985 990

Glu Leu Arg Leu Arg Gly Tyr Asp Tyr Gly Pro His Phe Gln Gly Ile

995 1000 1005

Leu Glu Ala Ser Leu Glu Gly Asp Ser Gly Arg Leu Leu Trp Lys

1010 1015 1020

Asp Asn Trp Val Ser Phe Met Asp Thr Met Leu Gln Met Ser Ile

1025 1030 1035

Leu Gly Ser Ala Lys His Gly Leu Tyr Leu Pro Thr Arg Val Thr

1040 1045 1050

Ala Ile His Ile Asp Pro Ala Thr His Arg Gln Lys Leu Tyr Thr

1055 1060 1065

Leu Gln Asp Lys Ala Gln Val Ala Asp Val Val Val Ser Arg Trp

1070 1075 1080

Leu Arg Val Thr Val Ala Gly Gly Val His Ile Ser Gly Leu His

1085 1090 1095

Thr Glu Ser Ala Pro Arg Arg Gln Gln Glu Gln Gln Val Pro Ile

1100 1105 1110

Leu Glu Lys Phe Cys Phe Thr Pro His Thr Glu Glu Gly Cys Leu

1115 1120 1125

Ser Glu Arg Ala Ala Leu Gln Glu Glu Leu Gln Leu Cys Lys Gly

1130 1135 1140

Leu Val Gln Ala Leu Gln Thr Lys Val Thr Gln Gln Gly Leu Lys

1145 1150 1155

Met Val Val Pro Gly Leu Asp Gly Ala Gln Ile Pro Arg Asp Pro

1160 1165 1170

Ser Gln Gln Glu Leu Pro Arg Leu Leu Ser Ala Ala Cys Arg Leu

1175 1180 1185

Gln Leu Asn Gly Asn Leu Gln Leu Glu Leu Ala Gln Val Leu Ala

1190 1195 1200

Gln Glu Arg Pro Lys Leu Pro Glu Asp Pro Leu Leu Ser Gly Leu

1205 1210 1215

Leu Asp Ser Pro Ala Leu Lys Ala Cys Leu Asp Thr Ala Val Glu

1220 1225 1230

Asn Met Pro Ser Leu Lys Met Lys Val Val Glu Val Leu Ala Gly

1235 1240 1245

His Gly His Leu Tyr Ser Arg Ile Pro Gly Leu Leu Ser Pro His

1250 1255 1260

Pro Leu Leu Gln Leu Ser Tyr Thr Ala Thr Asp Arg His Pro Gln

1265 1270 1275

Ala Leu Glu Ala Ala Gln Ala Glu Leu Gln Gln His Asp Val Ala

1280 1285 1290

Gln Gly Gln Trp Asp Pro Ala Asp Pro Ala Pro Ser Ala Leu Gly

1295 1300 1305

Ser Ala Asp Leu Leu Val Cys Asn Cys Ala Val Ala Ala Leu Gly

1310 1315 1320

Asp Pro Ala Ser Ala Leu Ser Asn Met Val Ala Ala Leu Arg Glu

1325 1330 1335

Gly Gly Phe Leu Leu Leu His Thr Leu Leu Arg Gly His Pro Leu

1340 1345 1350

Gly Asp Ile Val Ala Phe Leu Thr Ser Thr Glu Pro Gln Tyr Gly

1355 1360 1365

Gln Gly Ile Leu Ser Gln Asp Ala Trp Glu Ser Leu Phe Ser Arg

1370 1375 1380

Val Ser Leu Arg Leu Val Gly Leu Lys Lys Ser Phe Tyr Gly Ser

1385 1390 1395

Thr Leu Phe Leu Cys Arg Arg Pro Thr Pro Gln Asp Ser Pro Ile

1400 1405 1410

Phe Leu Pro Val Asp Asp Thr Ser Phe Arg Trp Val Glu Ser Leu

1415 1420 1425

Lys Gly Ile Leu Ala Asp Glu Asp Ser Ser Arg Pro Val Trp Leu

1430 1435 1440

Lys Ala Ile Asn Cys Ala Thr Ser Gly Val Val Gly Leu Val Asn

1445 1450 1455

Cys Leu Arg Arg Glu Pro Gly Gly Asn Arg Leu Arg Cys Val Leu

1460 1465 1470

Leu Ser Asn Leu Ser Ser Thr Ser His Val Pro Glu Val Asp Pro

1475 1480 1485

Gly Ser Ala Glu Leu Gln Lys Val Leu Gln Gly Asp Leu Val Met

1490 1495 1500

Asn Val Tyr Arg Asp Gly Ala Trp Gly Ala Phe Arg His Phe Leu

1505 1510 1515

Leu Glu Glu Asp Lys Pro Glu Glu Pro Thr Ala His Ala Phe Val

1520 1525 1530

Ser Thr Leu Thr Arg Gly Asp Leu Ser Ser Ile Arg Trp Val Cys

1535 1540 1545

Ser Ser Leu Arg His Ala Gln Pro Thr Cys Pro Gly Ala Gln Leu

1550 1555 1560

Cys Thr Val Tyr Tyr Ala Ser Leu Asn Phe Arg Asp Ile Met Leu

1565 1570 1575

Ala Thr Gly Lys Leu Ser Pro Asp Ala Ile Pro Gly Lys Trp Thr

1580 1585 1590

Ser Gln Asp Ser Leu Leu Gly Met Glu Phe Ser Gly Arg Asp Ala

1595 1600 1605

Ser Gly Lys Arg Val Met Gly Leu Val Pro Ala Lys Gly Leu Ala

1610 1615 1620

Thr Ser Val Leu Leu Ser Pro Asp Phe Leu Trp Asp Val Pro Ser

1625 1630 1635

Asn Trp Thr Leu Glu Glu Ala Ala Ser Val Pro Val Val Tyr Ser

1640 1645 1650

Thr Ala Tyr Tyr Ala Leu Val Val Arg Gly Arg Val Arg Pro Gly

1655 1660 1665

Glu Thr Leu Leu Ile His Ser Gly Ser Gly Gly Val Gly Gln Ala

1670 1675 1680

Ala Ile Ala Ile Ala Leu Ser Leu Gly Cys Arg Val Phe Thr Thr

1685 1690 1695

Val Gly Ser Ala Glu Lys Arg Ala Tyr Leu Gln Ala Arg Phe Pro

1700 1705 1710

Gln Leu Asp Ser Thr Ser Phe Ala Asn Ser Arg Asp Thr Ser Phe

1715 1720 1725

Glu Gln His Val Leu Trp His Thr Gly Gly Lys Gly Val Asp Leu

1730 1735 1740

Val Leu Asn Ser Leu Ala Glu Glu Lys Leu Gln Ala Ser Val Arg

1745 1750 1755

Cys Leu Ala Thr His Gly Arg Phe Leu Glu Ile Gly Lys Phe Asp

1760 1765 1770

Leu Ser Gln Asn His Pro Leu Gly Met Ala Ile Phe Leu Lys Asn

1775 1780 1785

Val Thr Phe His Gly Val Leu Leu Asp Ala Phe Phe Asn Glu Ser

1790 1795 1800

Ser Ala Asp Trp Arg Glu Val Trp Ala Leu Val Gln Ala Gly Ile

1805 1810 1815

Arg Asp Gly Val Val Arg Pro Leu Lys Cys Thr Val Phe His Gly

1820 1825 1830

Ala Gln Val Glu Asp Ala Phe Arg Tyr Met Ala Gln Gly Lys His

1835 1840 1845

Ile Gly Lys Val Val Val Gln Val Leu Ala Glu Glu Pro Glu Ala

1850 1855 1860

Val Leu Lys Gly Ala Lys Pro Lys Leu Met Ser Ala Ile Ser Lys

1865 1870 1875

Thr Phe Cys Pro Ala His Lys Ser Tyr Ile Ile Ala Gly Gly Leu

1880 1885 1890

Gly Gly Phe Gly Leu Glu Leu Ala Gln Trp Leu Ile Gln Arg Gly

1895 1900 1905

Val Gln Lys Leu Val Leu Thr Ser Arg Ser Gly Ile Arg Thr Gly

1910 1915 1920

Tyr Gln Ala Lys Gln Val Arg Arg Trp Arg Arg Gln Gly Val Gln

1925 1930 1935

Val Gln Val Ser Thr Ser Asn Ile Ser Ser Leu Glu Gly Ala Arg

1940 1945 1950

Gly Leu Ile Ala Glu Ala Ala Gln Leu Gly Pro Val Gly Gly Val

1955 1960 1965

Phe Asn Leu Ala Val Val Leu Arg Asp Gly Leu Leu Glu Asn Gln

1970 1975 1980

Thr Pro Glu Phe Phe Gln Asp Val Cys Lys Pro Lys Tyr Ser Gly

1985 1990 1995

Thr Leu Asn Leu Asp Arg Val Thr Arg Glu Ala Cys Pro Glu Leu

2000 2005 2010

Asp Tyr Phe Val Val Phe Ser Ser Val Ser Cys Gly Arg Gly Asn

2015 2020 2025

Ala Gly Gln Ser Asn Tyr Gly Phe Ala Asn Ser Ala Met Glu Arg

2030 2035 2040

Ile Cys Glu Lys Arg Arg His Glu Gly Leu Pro Gly Leu Ala Val

2045 2050 2055

Gln Trp Gly Ala Ile Gly Asp Val Gly Ile Leu Val Glu Thr Met

2060 2065 2070

Ser Thr Asn Asp Thr Ile Val Ser Gly Thr Leu Pro Gln Arg Met

2075 2080 2085

Ala Ser Cys Leu Glu Val Leu Asp Leu Phe Leu Asn Gln Pro His

2090 2095 2100

Met Val Leu Ser Ser Phe Val Leu Ala Glu Lys Ala Ala Ala Tyr

2105 2110 2115

Arg Asp Arg Asp Ser Gln Arg Asp Leu Val Glu Ala Val Ala His

2120 2125 2130

Ile Leu Gly Ile Arg Asp Leu Ala Ala Val Asn Leu Asp Ser Ser

2135 2140 2145

Leu Ala Asp Leu Gly Leu Asp Ser Leu Met Ser Val Glu Val Arg

2150 2155 2160

Gln Thr Leu Glu Arg Glu Leu Asn Leu Val Leu Ser Val Arg Glu

2165 2170 2175

Val Arg Gln Leu Thr Leu Arg Lys Leu Gln Glu Leu Ser Ser Lys

2180 2185 2190

Ala Asp Glu Ala Ser Glu Leu Ala Cys Pro Thr Pro Lys Glu Asp

2195 2200 2205

Gly Leu Ala Gln Gln Gln Thr Gln Leu Asn Leu Arg Ser Leu Leu

2210 2215 2220

Val Asn Pro Glu Gly Pro Thr Leu Met Arg Leu Asn Ser yal Gln

2225 2230 2235

Ser Ser Glu Arg Pro Leu Phe Leu Val His Pro Ile Glu Gly Ser

2240 2245 2250

Thr Thr Val Phe His Ser Leu Ala Ser Arg Leu Ser Ile Pro Thr

2255 2260 2265

Tyr Gly Leu Gln Cys Thr Arg Ala Ala Pro Leu Asp Ser Ile His

2270 2275 2280

Ser Leu Ala Ala Tyr Tyr Ile Asp Cys Ile Arg Gln Val Gln Pro

2285 2290 2295

Glu Gly Pro Tyr Arg Val Ala Gly Tyr Ser Tyr Gly Ala Cys Val

2300 2305 2310

Ala Phe Glu Met Cys Ser Gln Leu Gln Ala Gln Gln Ser Pro Ala

2315 2320 2325

Pro Thr His Asn Ser Leu Phe Leu Phe Asp Gly Ser Pro Thr Tyr

2330 2335 2340

Val Leu Ala Tyr Thr Gln Ser Tyr Arg Ala Lys Leu Thr Pro Gly

2345 2350 2355

Cys Glu Ala Glu Ala Glu Thr Glu Ala Ile Cys Phe Phe Val Gln

2360 2365 2370

Gln Phe Thr Asp Met Glu His Asn Arg Val Leu Glu Ala Leu Leu

2375 2380 2385

Pro Leu Lys Gly Leu Glu Glu Arg Val Ala Ala Ala Val Asp Leu

2390 2395 2400

Ile Ile Lys Ser His Gln Gly Leu Asp Arg Gln Glu Leu Ser Phe

2405 2410 2415

Ala Ala Arg Ser Phe Tyr Tyr Lys Leu Arg Ala Ala Glu Gln Tyr

2420 2425 2430

Thr Pro Lys Ala Lys Tyr His Gly Asn Val Met Leu Leu Arg Ala

2435 2440 2445

Lys Thr Gly Gly Ala Tyr Gly Glu Asp Leu Gly Ala Asp Tyr Asn

2450 2455 2460

Leu Ser Gln Val Cys Asp Gly Lys Val Ser Val His Val Ile Glu

2465 2470 2475

Gly Asp His Arg Thr Leu Leu Glu Gly Ser Gly Leu Glu Ser Ile

2480 2485 2490

Ile Ser Ile Ile His Ser Ser Leu Ala Glu Pro Arg Val Ser Val

2495 2500 2505

Arg Glu Gly

2510

<210>65

<211>387

<212>PRT

<213>人(Homo sapiens)

<400>65

Met Ser Thr Phe Phe Ser Asp Thr Ala Trp Ile Cys Leu Ala Val Pro

1 5 10 15

Thr Val Leu Cys Gly Thr Val Phe Cys Lys Tyr Lys Lys Ser Ser Gly

20 25 30

Gln Leu Trp Ser Trp Met Val Cys Leu Ala Gly Leu Cys Ala Val Cys

35 40 45

Leu Leu Ile Leu Ser Pro Phe Trp Gly Leu Ile Leu Phe Ser Val Ser

50 55 60

Cys Phe Leu Met Tyr Thr Tyr Leu Ser Gly Gln Glu Leu Leu Pro Val

65 70 75 80

Asp Gln Lys Ala Val Leu Val Thr Gly Gly Asp Cys Gly Leu Gly His

85 90 95

Ala Leu Cys Lys Tyr Leu Asp Glu Leu Gly Phe Thr Val Phe Ala Gly

100 105 110

Val Leu Asn Glu Asn Gly Pro Gly Ala Glu Glu Leu Arg Arg Thr Cys

115 120 125

Ser Pro Arg Leu Ser Val Leu Gln Met Asp Ile Thr Lys Pro Val Gln

130 135 140

Ile Lys Asp Ala Tyr Ser Lys Val Ala Ala Met Leu Gln Asp Arg Gly

145 150 155 160

Leu Trp Ala Val Ile Asn Asn Ala Gly Val Leu Gly Phe Pro Thr Asp

165 170 175

Gly Glu Leu Leu Leu Met Thr Asp Tyr Lys Gln Cys Met Ala Val Asn

180 185 190

Phe Phe Gly Thr Val Glu Val Thr Lys Thr Phe Leu Pro Leu Leu Arg

195 200 205

Lys Ser Lys Gly Arg Leu Val Asn Val Ser Ser Met Gly Gly Gly Ala

210 215 220

Pro Met Glu Arg Leu Ala Ser Tyr Gly Ser Ser Lys Ala Ala Val Thr

225 230 235 240

Met Phe Ser Ser Val Met Arg Leu Glu Leu Ser Lys Trp Gly Ile Lys

245 250 255

Val Ala Ser Ile Gln Pro Gly Gly Phe Leu Thr Asn Ile Ala Gly Thr

260 265 270

Ser Asp Lys Trp Glu Lys Leu Glu Lys Asp Ile Leu Asp His Leu Pro

275 280 285

Ala Glu Val Gln Glu Asp Tyr Gly Gln Asp Tyr Ile Leu Ala Gln Arg

290 295 300

Asn Phe Leu Leu Leu Ile Asn Ser Leu Ala Ser Lys Asp Phe Ser Pro

305 310 315 320

Val Leu Arg Asp Ile Gln His Ala Ile Leu Ala Lys Ser Pro Phe Ala

325 330 335

Tyr Tyr Thr Pro Gly Lys Gly Ala Tyr Leu Trp Ile Cys Leu Ala His

340 345 350

Tyr Leu Pro Ile Gly Ile Tyr Asp Tyr Phe Ala Lys Arg His Phe Gly

355 360 365

Gln Asp Lys Pro Met Pro Arg Ala Leu Arg Met Pro Asn Tyr Lys Lys

370 375 380

Lys Ala Thr

385

<210>66

<211>294

<212>PRT

<213>人(Homo sapiens)

<400>66

Met Asn Ser Glu Leu Asp Tyr Tyr Glu Lys Phe Glu Glu Val His Gly

1 5 10 15

Ile Leu Met Tyr Lys Asp Phe Val Lys Tyr Trp Asp Asn Val Glu Ala

20 25 30

Phe Gln Ala Arg Pro Asp Asp Leu Val Ile Ala Thr Tyr Pro Lys Ser

35 40 45

Gly Thr Thr Trp Val Ser Glu Ile Val Tyr Met Ile Tyr Lys Glu Gly

50 55 60

Asp Val Glu Lys Cys Lys Glu Asp Val Ile Phe Asn Arg Ile Pro Phe

65 70 75 80

Leu Glu Cys Arg Lys Glu Asn Leu Met Asn Gly Val Lys Gln Leu Asp

85 90 95

Glu Met Asn Ser Pro Arg Ile Val Lys Thr His Leu Pro Pro Glu Leu

100 105 110

Leu Pro Ala Ser Phe Trp Glu Lys Asp Cys Lys Ile Ile Tyr Leu Cys

115 120 125

Arg Asn Ala Lys Asp Val Ala Val Ser Phe Tyr Tyr Phe Phe Leu Met

130 135 140

Val Ala Gly His Pro Asn Pro Gly Ser Phe Pro Glu Phe Val Glu Lys

145 150 155 160

Phe Met Gln Gly Gln Val Pro Tyr Gly Ser Trp Tyr Lys His Val Lys

165 170 175

Ser Trp Trp Glu Lys Gly Lys Ser Pro Arg Val Leu Phe Leu Phe Tyr

180 185 190

Glu Asp Leu Lys Glu Asp Ile Arg Lys Glu Val Ile Lys Leu Ile His

195 200 205

Phe Leu Glu Arg Lys Pro Ser Glu Glu Leu Val Asp Arg Ile Ile His

210 215 220

His Thr Ser Phe Gln Glu Met Lys Asn Asn Pro Ser Thr Asn Tyr Thr

225 230 235 240

Thr Leu Pro Asp Glu Ile Met Asn Gln Lys Leu Ser Pro Phe Met Arg

245 250 255

Lys Gly Ile Thr Gly Asp Trp Lys Asn His Phe Thr Val Ala Leu Asn

260 265 270

Glu Lys Phe Asp Lys His Tyr Glu Gln Gln Met Lys Glu Ser Thr Leu

275 280 285

Lys Phe Arg Thr Glu Ile

290

<210>67

<211>487

<212>PRT

<213>人(Homo sapiens)

<400>67

Met Ser Lys Leu Leu Arg His Arg Arg Lys His Asp Asp Asp Arg Arg

1 5 10 15

Phe Thr Cys Pro Val Glu Gly Cys Gly Lys Ser Phe Thr Arg Ala Glu

20 25 30

His Leu Lys Gly His Ser Ile Thr His Leu Gly Thr Lys Pro Phe Glu

35 40 45

Cys Pro Val Glu Gly Cys Cys Ala Arg Phe Ser Ala Arg Ser Ser Leu

50 55 60

Tyr Ile His Ser Lys Lys His Val Gln Asp Val Gly Ala Pro Lys Ser

65 70 75 80

Arg Cys Pro Val Ser Thr Cys Asn Arg Leu Phe Thr Ser Lys His Ser

85 90 95

Met Lys Ala His Met Val Arg Gln His Ser Arg Arg Gln Asp Leu Leu

100 105 110

Pro Gln Leu Glu Ala Pro Ser Ser Leu Thr Pro Ser Ser Glu Leu Ser

115 120 125

Ser Pro Gly Gln Ser Glu Leu Thr Asn Met Asp Leu Ala Ala Leu Phe

130 135 140

Ser Asp Thr Pro Ala Asn Ala Ser Gly Ser Ala Gly Gly Ser Asp Glu

145 150 155 160

Ala Leu Asn Ser Gly Ile Leu Thr Ile Asp Val Thr Ser Val Ser Ser

165 170 175

Ser Leu Gly Gly Asn Leu Pro Ala Asn Asn Ser Ser Leu Gly Pro Met

180 185 190

Glu Pro Leu Val Leu Val Ala His Ser Asp Ile Pro Pro Ser Leu Asp

195 200 205

Ser Pro Leu Val Leu Gly Thr Ala Ala Thr Val Leu Gln Gln Gly Ser

210 215 220

Phe Ser Val Asp Asp Val Gln Thr Val Ser Ala Gly Ala Leu Gly Cys

225 230 235 240

Leu Val Ala Leu Pro Met Lys Asn Leu Ser Asp Asp Pro Leu Ala Leu

245 250 255

Thr Ser Asn Ser Asn Leu Ala Ala His Ile Thr Thr Pro Thr Ser Ser

260 265 270

Ser Thr Pro Arg Glu Asn Ala Ser Val Pro Glu Leu Leu Ala Pro Ile

275 280 285

Lys Val Glu Pro Asp Ser Pro Ser Arg Pro Gly Ala Val Gly Gln Gln

290 295 300

Glu Gly Ser His Gly Leu Pro Gln Ser Thr Leu Pro Ser Pro Ala Glu

305 310 315 320

Gln His Gly Ala Gln Asp Thr Glu Leu Ser Ala Gly Thr Gly Asn Phe

325 330 335

Tyr Leu Glu Ser Gly Gly Ser Ala Arg Thr Asp Tyr Arg Ala Ile Gln

340 345 350

Leu Ala Lys Glu Lys Lys Gln Arg Gly Ala Gly Ser Asn Ala Gly Ala

355 360 365

Ser Gln Ser Thr Gln Arg Lys Ile Lys Glu Gly Lys Met Ser Pro Pro

370 375 380

His Phe His Ala Ser Gln Asn Ser Trp Leu Cys Gly Ser Leu Val Val

385 390 395 400

Pro Ser Gly Gly Arg Pro Gly Pro Ala Pro Ala Ala Gly Val Gln Cys

405 410 415

Gly Ala Gln Gly Val Gln Val Gln Leu Val Gln Asp Asp Pro Ser Gly

420 425 430

Glu Gly Val Leu Pro Ser Ala Arg Gly Pro Ala Thr Phe Leu Pro Phe

435 440 445

Leu Thr Val Asp Leu Pro Val Tyr Val Leu Gln Glu Val Leu Pro Ser

450 455 460

Ser Gly Gly Pro Ala Gly Pro Glu Ala Thr Gln Phe Pro Gly Ser Thr

465 470 475 480

Ile Asn Leu Gln Asp Leu Gln

485

<210>68

<211>114

<212>PRT

<213>人(Homo sapiens)

<400>68

Met Thr Cys Lys Met Ser Gln Leu Glu Arg Asn Ile Glu Thr Ile Ile

1 5 10 15

Asn Thr Phe His Gln Tyr Ser Val Lys Leu Gly His Pro Asp Thr Leu

20 25 30

Asn Gln Gly Glu Phe Lys Glu Leu Val Arg Lys Asp Leu Gln Asn Phe

35 40 45

Leu Lys Lys Glu Asn Lys Asn Glu Lys Val Ile Glu His Ile Met Glu

50 55 60

Asp Leu Asp Thr Asn Ala Asp Lys Gln Leu Ser Phe Glu Glu Phe Ile

65 70 75 80

Met Leu Met Ala Arg Leu Thr Trp Ala Ser His Glu Lys Met His Glu

85 90 95

Gly Asp Glu Gly Pro Gly His His His Lys Pro Gly Leu Gly Glu Gly

100 105 110

Thr Pro

<210>69

<211>501

<212>PRT

<213>人(Homo sapiens)

<400>69

Met Ser Ser Ser Gly Thr Pro Asp Leu Pro Val Leu Leu Thr Asp Leu

1 5 10 15

Lys Ile Gln Tyr Thr Lys Ile Phe Ile Asn Asn Glu Trp His Asp Ser

20 25 30

Val Ser Gly Lys Lys Phe Pro Val Phe Asn Pro Ala Thr Glu Glu Glu

35 40 45

Leu Cys Gln Val Glu Glu Gly Asp Lys Glu Asp Val Asp Lys Ala Val

50 55 60

Lys Ala Ala Arg Gln Ala Phe Gln Ile Gly Ser Pro Trp Arg Thr Met

65 70 75 80

Asp Ala Ser Glu Arg Gly Arg Leu Leu Tyr Lys Leu Ala Asp Leu Ile

85 90 95

Glu Arg Asp Arg Leu Leu Leu Ala Thr Met Glu Ser Met Asn Gly Gly

100 105 110

Lys Leu Tyr Ser Asn Ala Tyr Leu Asn Asp Leu Ala Gly Cys Ile Lys

115 120 125

Thr Leu Arg Tyr Cys Ala Gly Trp Ala Asp Lys Ile Gln Gly Arg Thr

130 135 140

Ile Pro Ile Asp Gly Asn Phe Phe Thr Tyr Thr Arg His Glu Pro Ile

145 150 155 160

Gly Val Cys Gly Gln Ile Ile Pro Trp Asn Phe Pro Leu Val Met Leu

165 170 175

Ile Trp Lys Ile Gly Pro Ala Leu Ser Cys Gly Asn Thr Val Val Val

180 185 190

Lys Pro Ala Glu Gln Thr Pro Leu Thr Ala Leu His Val Ala Ser Leu

195 200 205

Ile Lys Glu Ala Gly Phe Pro Pro Gly Val Val Asn Ile Val Pro Gly

210 215 220

Tyr Gly Pro Thr Ala Gly Ala Ala Ile Ser Ser His Met Asp Ile Asp

225 230 235 240

Lys Val Ala Phe Thr Gly Ser Thr Glu Val Gly Lys Leu Ile Lys Glu

245 250 255

Ala Ala Gly Lys Ser Asn Leu Lys Arg Val Thr Leu Glu Leu Gly Gly

260 265 270

Lys Ser Pro Cys Ile Val Leu Ala Asp Ala Asp Leu Asp Asn Ala Val

275 280 285

Glu Phe Ala His His Gly Val Phe Tyr His Gln Gly Gln Cys Cys Ile

290 295 300

Ala Ala Ser Arg Ile Phe Val Glu Glu Ser Ile Tyr Asp Glu Phe Val

305 310 315 320

Arg Arg Ser Val Glu Arg Ala Lys Lys Tyr Ile Leu Gly Asn Pro Leu

325 330 335

Thr Pro Gly Val Thr Gln Gly Pro Gln Ile Asp Lys Glu Gln Tyr Asp

340 345 350

Lys Ile Leu Asp Leu Ile Glu Ser Gly Lys Lys Glu Gly Ala Lys Leu

355 360 365

Glu Cys Gly Gly Gly Pro Trp Gly Asn Lys Gly Tyr Phe Val Gln Pro

370 375 380

Thr Val Phe Ser Asn Val Thr Asp Glu Met Arg Ile Ala Lys Glu Glu

385 390 395 400

Ile Phe Gly Pro Val Gln Gln Ile Met Lys Phe Lys Ser Leu Asp Asp

405 410 415

Val Ile Lys Arg Ala Asn Asn Thr Phe Tyr Gly Leu Ser Ala Gly Val

420 425 430

Phe Thr Lys Asp Ile Asp Lys Ala Ile Thr Ile Ser Ser Ala Leu Gln

435 440 445

Ala Gly Thr Val Trp Val Asn Cys Tyr Gly Val Val Ser Ala Gln Cys

450 455 460

Pro Phe Gly Gly Phe Lys Met Ser Gly Asn Gly Arg Glu Leu Gly Glu

465 470 475 480

Tyr Gly Phe His Glu Tyr Thr Glu Val Lys Thr Val Thr Val Lys Ile

485 490 495

Ser Gln Lys Asn Ser

500

<210>70

<211>204

<212>PRT

<213>人(Homo sapiens)

<400>70

Met Ala Glu Gln Glu Pro Thr Ala Glu Gln Leu Ala Gln Ile Ala Ala

1 5 10 15

Glu Asn Glu Glu Asp Glu His Ser Val Asn Tyr Lys Pro Pro Ala Gln

20 25 30

Lys Ser Ile Gln Glu Ile Gln Glu Leu Asp Lys Asp Asp Glu Ser Leu

35 40 45

Arg Lys Tyr Lys Glu Ala Leu Leu Gly Arg Val Ala Val Ser Ala Asp

50 55 60

Pro Asn Val Pro Asn Val Val Val Thr Gly Leu Thr Leu Val Cys Ser

65 70 75 80

Ser Ala Pro Gly Pro Leu Glu Leu Asp Leu Thr Gly Asp Leu Glu Ser

85 90 95

Phe Lys Lys Gln Ser Phe Val Leu Lys Glu Gly Val Glu Tyr Arg Ile

100 105 110

Lys Ile Ser Phe Arg Val Asn Arg Glu Ile Val Ser Gly Met Lys Tyr

115 120 125

Ile Gln His Thr Tyr Arg Lys Gly Val Lys Ile Asp Lys Thr Asp Tyr

130 135 140

Met Val Gly Ser Tyr Gly Pro Arg Ala Glu Glu Tyr Glu Phe Leu Thr

145 150 155 160

Pro Val Glu Glu Ala Pro Lys Gly Met Leu Ala Arg Gly Ser Tyr Ser

165 170 175

Ile Lys Ser Arg Phe Thr Asp Asp Asp Lys Thr Asp His Leu Ser Trp

180 185 190

Glu Trp Asn Leu Thr Ile Lys Lys Asp Trp Lys Asp

195 200

<210>71

<211>261

<212>PRT

<213>人(Homo sapiens)

<400>71

Met Ala Ser Pro Asp Trp Gly Tyr Asp Asp Lys Asn Gly Pro Glu Gln

1 5 10 15

Trp Ser Lys Leu Tyr Pro Ile Ala Asn Gly Asn Asn Gln Ser Pro Val

20 25 30

Asp Ile Lys Thr Ser Glu Thr Lys His Asp Thr Ser Leu Lys Pro Ile

35 40 45

Ser Val Ser Tyr Asn Pro Ala Thr Ala Lys Glu Ile Ile Asn Val Gly

50 55 60

His Ser Phe His Val Asn Phe Glu Asp Asn Asp Asn Arg Ser Val Leu

65 70 75 80

Lys Gly Gly Pro Phe Ser Asp Ser Tyr Arg Leu Phe Gln Phe His Phe

85 90 95

His Trp Gly Ser Thr Asn Glu His Gly Ser Glu His Thr Val Asp Gly

100 105 110

Val Lys Tyr Ser Ala Glu Leu His Val Ala His Trp Asn Ser Ala Lys

115 120 125

Tyr Ser Ser Leu Ala Glu Ala Ala Ser Lys Ala Asp Gly Leu Ala Val

130 135 140

Ile Gly Val Leu Met Lys Val Gly Glu Ala Asn Pro Lys Leu Gln Lys

145 150 155 160

Val Leu Asp Ala Leu Gln Ala Ile Lys Thr Lys Gly Lys Arg Ala Pro

165 170 175

Phe Thr Asn Phe Asp Pro Ser Thr Leu Leu Pro Ser Ser Leu Asp Phe

180 185 190

Trp Thr Tyr Pro Gly Ser Leu Thr His Pro Pro Leu Tyr Glu Ser Val

195 200 205

Thr Trp Ile Ile Cys Lys Glu Ser Ile Ser Val Ser Ser Glu Gln Leu

210 215 220

Ala Gln Phe Arg Ser Leu Leu Ser Asn Val Glu Gly Asp Asn Ala Val

225 230 235 240

Pro Met Gln His Asn Asn Arg Pro Thr Gln Pro Leu Lys Gly Arg Thr

245 250 255

Val Arg Ala Ser Phe

260

<210>72

<211>260

<212>PRT

<213>人(Homo sapiens)

<400>72

Met Ser His His Trp Gly Tyr Gly Lys His Asn Gly Pro Glu His Trp

1 5 10 15

His Lys Asp Phe Pro Ile Ala Lys Gly Glu Arg Gln Ser Pro Val Asp

20 25 30

Ile Asp Thr His Thr Ala Lys Tyr Asp Pro Ser Leu Lys Pro Leu Ser

35 40 45

Val Ser Tyr Asp Gln Ala Thr Ser Leu Arg Ile Leu Asn Asn Gly His

50 55 60

Ala Phe Asn Val Glu Phe Asp Asp Ser Gln Asp Lys Ala Val Leu Lys

65 70 75 80

Gly Gly Pro Leu Asp Gly Thr Tyr Arg Leu Ile Gln Phe His Phe His

85 90 95

Trp Gly Ser Leu Asp Gly Gln Gly Ser Glu His Thr Val Asp Lys Lys

100 105 110

Lys Tyr Ala Ala Glu Leu His Leu Val His Trp Asn Thr Lys Tyr Gly

115 120 125

Asp Phe Gly Lys Ala Val Gln Gln Pro Asp Gly Leu Ala Val Leu Gly

130 135 140

Ile Phe Leu Lys Val Gly Ser Ala Lys Pro Gly Leu Gln Lys Val Val

145 150 155 160

Asp Val Leu Asp Ser Ile Lys Thr Lys Gly Lys Ser Ala Asp Phe Thr

165 170 175

Asn Phe Asp Pro Arg Gly Leu Leu Pro Glu Ser Leu Asp Tyr Trp Thr

180 185 190

Tyr Pro Gly Ser Leu Thr Thr Pro Pro Leu Leu Glu Cys Val Thr Trp

195 200 205

Ile Val Leu Lys Glu Pro Ile Ser Val Ser Ser Glu Gln Val Leu Lys

210 215 220

Phe Arg Lys Leu Asn Phe Asn Gly Glu Gly Glu Pro Glu Glu Leu Met

225 230 235 240

Val Asp Asn Trp Arg Pro Ala Gln Pro Leu Lys Asn Arg Gln Ile Lys

245 250 255

Ala Ser Phe Lys

260

<210>73

<211>609

<212>PRT

<213>人(Homo sapiens)

<400>73

Met Ser Gly Trp Glu Ser Tyr Tyr Lys Thr Glu Gly Asp Glu Glu Ala

1 5 10 15

Glu Glu Glu Gln Glu Glu Asn Leu Glu Ala Ser Gly Asp Tyr Lys Tyr

20 25 30

Ser Gly Arg Asp Ser Leu Ile Phe Leu Val Asp Ala Ser Lys Ala Met

35 40 45

Phe Glu Ser Gln Ser Glu Asp Glu Leu Thr Pro Phe Asp Met Ser Ile

50 55 60

Gln Cys Ile Gln Ser Val Tyr Ile Ser Lys Ile Ile Ser Ser Asp Arg

65 70 75 80

Asp Leu Leu Ala Val Val Phe Tyr Gly Thr Glu Lys Asp Lys Asn Ser

85 90 95

Val Asn Phe Lys Asn Ile Tyr Val Leu Gln Glu Leu Asp Asn Pro Gly

100 105 110

Ala Lys Arg Ile Leu Glu Leu Asp Gln Phe Lys Gly Gln Gln Gly Gln

115 120 125

Lys Arg Phe Gln Asp Met Met Gly His Gly Ser Asp Tyr Ser Leu Ser

130 135 140

Glu Val Leu Trp Val Cys Ala Asn Leu Phe Ser Asp Val Gln Phe Lys

145 150 155 160

Met Ser His Lys Arg Ile Met Leu Phe Thr Asn Glu Asp Asn Pro His

165 170 175

Gly Asn Asp Ser Ala Lys Ala Ser Arg Ala Arg Thr Lys Ala Gly Asp

180 185 190

Leu Arg Asp Thr Gly Ile Phe Leu Asp Leu Met His Leu Lys Lys Pro

195 200 205

Gly Gly Phe Asp Ile Ser Leu Phe Tyr Arg Asp Ile Ile Ser Ile Ala

210 215 220

Glu Asp Glu Asp Leu Arg Val His Phe Glu Glu Ser Ser Lys Leu Glu

225 230 235 240

Asp Leu Leu Arg Lys Val Arg Ala Lys Glu Thr Arg Lys Arg Ala Leu

245 250 255

Ser Arg Leu Lys Leu Lys Leu Asn Lys Asp Ile Val Ile Ser Val Gly

260 265 270

Ile Tyr Asn Leu Val Gln Lys Ala Leu Lys Pro Pro Pro Ile Lys Leu

275 280 285

Tyr Arg Glu Thr Asn Glu Pro Val Lys Thr Lys Thr Arg Thr Phe Asn

290 295 300

Thr Ser Thr Gly Gly Leu Leu Leu Pro Ser Asp Thr Lys Arg Ser Gln

305 310 315 320

Ile Tyr Gly Ser Arg Gln Ile Ile Leu Glu Lys Glu Glu Thr Glu Glu

325 330 335

Leu Lys Arg Phe Asp Asp Pro Gly Leu Met Leu Met Gly Phe Lys Pro

340 345 350

Leu Val Leu Leu Lys Lys His His Tyr Leu Arg Pro Ser Leu Phe Val

355 360 365

Tyr Pro Glu Glu Ser Leu Val Ile Gly Ser Ser Thr Leu Phe Ser Ala

370 375 380

Leu Leu Ile Lys Cys Leu Glu Lys Glu Val Ala Ala Leu Cys Arg Tyr

385 390 395 400

Thr Pro Arg Arg Asn Ile Pro Pro Tyr Phe Val Ala Leu Val Pro Gln

405 410 415

Glu Glu Glu Leu Asp Asp Gln Lys Ile Gln Val Thr Pro Pro Gly Phe

420 425 430

Gln Leu Val Phe Leu Pro Phe Ala Asp Asp Lys Arg Lys Met Pro Phe

435 440 445

Thr Glu Lys Ile Met Ala Thr Pro Glu Gln Val Gly Lys Met Lys Ala

450 455 460

Ile Val Glu Lys Leu Arg Phe Thr Tyr Arg Ser Asp Ser Phe Glu Asn

465 470 475 480

Pro Val Leu Gln Gln His Phe Arg Asn Leu Glu Ala Leu Ala Leu Asp

485 490 495

Leu Met Glu Pro Glu Gln Ala Val Asp Leu Thr Leu Pro Lys Val Glu

500 505 510

Ala Met Asn Lys Arg Leu Gly Ser Leu Val Asp Glu Phe Lys Glu Leu

515 520 525

Val Tyr Pro Pro Asp Tyr Asn Pro Glu Gly Lys Val Thr Lys Arg Lys

530 535 540

His Asp Asn Glu Gly Ser Gly Ser Lys Arg Pro Lys Val Glu Tyr Ser

545 550 555 560

Glu Glu Glu Leu Lys Thr His Ile Ser Lys Gly Thr Leu Gly Lys Phe

565 570 575

Thr Val Pro Met Leu Lys Glu Ala Cys Arg Ala Tyr Gly Leu Lys Ser

580 585 590

Gly Leu Lys Lys Gln Glu Leu Leu Glu Ala Leu Thr Lys His Phe Gln

595 600 605

Asp

<210>74

<211>1960

<212>PRT

<213>人(Homo sapiens)

<400>74

Met Ala Gln Gln Ala Ala Asp Lys Tyr Leu Tyr Val Asp Lys Asn Phe

1 5 10 15

Ile Asn Asn Pro Leu Ala Gln Ala Asp Trp Ala Ala Lys Lys Leu Val

20 25 30

Trp Val Pro Ser Asp Lys Ser Gly Phe Glu Pro Ala Ser Leu Lys Glu

35 40 45

Glu Val Gly Glu Glu Ala Ile Val Glu Leu Val Glu Asn Gly Lys Lys

50 55 60

Val Lys Val Asn Lys Asp Asp Ile Gln Lys Met Asn Pro Pro Lys Phe

65 70 75 80

Ser Lys Val Glu Asp Met Ala Glu Leu Thr Cys Leu Asn Glu Ala Ser

85 90 95

Val Leu His Asn Leu Lys Glu Arg Tyr Tyr Ser Gly Leu Ile Tyr Thr

100 105 110

Tyr Ser Gly Leu Phe Cys Val Val Ile Asn Pro Tyr Lys Asn Leu Pro

115 120 125

Ile Tyr Ser Glu Glu Ile Val Glu Met Tyr Lys Gly Lys Lys Arg His

130 135 140

Glu Met Pro Pro His Ile Tyr Ala Ile Thr Asp Thr Ala Tyr Arg Ser

145 150 155 160

Met Met Gln Asp Arg Glu Asp Gln Ser Ile Leu Cys Thr Gly Glu Ser

165 170 175

Gly Ala Gly Lys Thr Glu Asn Thr Lys Lys Val Ile Gln Tyr Leu Ala

180 185 190

Tyr Val Ala Ser Ser His Lys Ser Lys Lys Asp Gln Gly Glu Leu Glu

195 200 205

Arg Gln Leu Leu Gln Ala Asn Pro Ile Leu Glu Ala Phe Gly Asn Ala

210 215 220

Lys Thr Val Lys Asn Asp Asn Ser Ser Arg Phe Gly Lys Phe Ile Arg

225 230 235 240

Ile Asn Phe Asp Val Asn Gly Tyr Ile Val Gly Ala Asn Ile Glu Thr

245 250 255

Tyr Leu Leu Glu Lys Ser Arg Ala Ile Arg Gln Ala Lys Glu Glu Arg

260 265 270

Thr Phe His Ile Phe Tyr Tyr Leu Leu Ser Gly Ala Gly Glu His Leu

275 280 285

Lys Thr Asp Leu Leu Leu Glu Pro Tyr Asn Lys Tyr Arg Phe Leu Ser

290 295 300

Asn Gly His Val Thr Ile Pro Gly Gln Gln Asp Lys Asp Met Phe Gln

305 310 315 320

Glu Thr Met Glu Ala Met Arg Ile Met Gly Ile Pro Glu Glu Glu Gln

325 330 335

Met Gly Leu Leu Arg Val Ile Ser Gly Val Leu Gln Leu Gly Asn Ile

340 345 350

Val Phe Lys Lys Glu Arg Asn Thr Asp Gln Ala Ser Met Pro Asp Asn

355 360 365

Thr Ala Ala Gln Lys Val Ser His Leu Leu Gly Ile Asn Val Thr Asp

370 375 380

Phe Thr Arg Gly Ile Leu Thr Pro Arg Ile Lys Val Gly Arg Asp Tyr

385 390 395 400

Val Gln Lys Ala Gln Thr Lys Glu Gln Ala Asp Phe Ala Ile Glu Ala

405 410 415

Leu Ala Lys Ala Thr Tyr Glu Arg Met Phe Arg Trp Leu Val Leu Arg

420 425 430

Ile Asn Lys Ala Leu Asp Lys Thr Lys Arg Gln Gly Ala Ser Phe Ile

435 440 445

Gly Ile Leu Asp Ile Ala Gly Phe Glu Ile Phe Asp Leu Asn Ser Phe

450 455 460

Glu Gln Leu Cys Ile Asn Tyr Thr Asn Glu Lys Leu Gln Gln Leu Phe

465 470 475 480

Asn His Thr Met Phe Ile Leu Glu Gln Glu Glu Tyr Gln Arg Glu Gly

485 490 495

Ile Glu Trp Asn Phe Ile Asp Phe Gly Leu Asp Leu Gln Pro Cys Ile

500 505 510

Asp Leu Ile Glu Lys Pro Ala Gly Pro Pro Gly Ile Leu Ala Leu Leu

515 520 525

Asp Glu Glu Cys Trp Phe Pro Lys Ala Thr Asp Lys Ser Phe Val Glu

530 535 540

Lys Val Met Gln Glu Gln Gly Thr His Pro Lys Phe Gln Lys Pro Lys

545 550 555 560

Gln Leu Lys Asp Lys Ala Asp Phe Cys Ile Ile His Tyr Ala Gly Lys

565 570 575

Val Asp Tyr Lys Ala Asp Glu Trp Leu Met Lys Asn Met Asp Pro Leu

580 585 590

Asn Asp Asn Ile Ala Thr Leu Leu Hi s Gln Ser Ser Asp Lys Phe Val

595 600 605

Ser Glu Leu Trp Lys Asp Val Asp Arg Ile Ile Gly Leu Asp Gln Val

610 615 620

Ala Gly Met Ser Glu Thr Ala Leu Pro Gly Ala Phe Lys Thr Arg Lys

625 630 635 640

Gly Met Phe Arg Thr Val Gly Gln Leu Tyr Lys Glu Gln Leu Ala Lys

645 650 655

Leu Met Ala Thr Leu Arg Asn Thr Asn Pro Asn Phe Val Arg Cys Ile

660 665 670

Ile Pro Asn His Glu Lys Lys Ala Gly Lys Leu Asp Pro His Leu Val

675 680 685

Leu Asp Gln Leu Arg Cys Asn Gly Val Leu Glu Gly Ile Arg Ile Cys

690 695 700

Arg Gln Gly Phe Pro Asn Arg Val Val Phe Gln Glu Phe Arg Gln Arg

705 710 715 720

Tyr Glu Ile Leu Thr Pro Asn Ser Ile Pro Lys Gly Phe Met Asp Gly

725 730 735

Lys Gln Ala Cys Val Leu Met Ile Lys Ala Leu Glu Leu Asp Ser Asn

740 745 750

Leu Tyr Arg Ile Gly Gln Ser Lys Val Phe Phe Arg Ala Gly Val Leu

755 760 765

Ala His Leu Glu Glu Glu Arg Asp Leu Lys Ile Thr Asp Val Ile Ile

770 775 780

Gly Phe Gln Ala Cys Cys Arg Gly Tyr Leu Ala Arg Lys Ala Phe Ala

785 790 795 800

Lys Arg Gln Gln Gln Leu Thr Ala Met Lys Val Leu Gln Arg Asn Cys

805 810 815

Ala Ala Tyr Leu Lys Leu Arg Asn Trp Gln Trp Trp Arg Leu Phe Thr

820 825 830

Lys Val Lys Pro Leu Leu Gln Val Ser Arg Gln Glu Glu Glu Met Met

835 840 845

Ala Lys Glu Glu Glu Leu Val Lys Val Arg Glu Lys Gln Leu Ala Ala

850 855 860

Glu Asn Arg Leu Thr Glu Met Glu Thr Leu Gln Ser Gln Leu Met Ala

865 870 875 880

Glu Lys Leu Gln Leu Gln Glu Gln Leu Gln Ala Glu Thr Glu Leu Cys

885 890 895

Ala Glu Ala Glu Glu Leu Arg Ala Arg Leu Thr Ala Lys Lys Gln Glu

900 905 910

Leu Glu Glu Ile Cys His Asp Leu Glu Ala Arg Val Glu Glu Glu Glu

915 920 925

Glu Arg Cys Gln His Leu Gln Ala Glu Lys Lys Lys Met Gln Gln Asn

930 935 940

Ile Gln Glu Leu Glu Glu Gln Leu Glu Glu Glu Glu Ser Ala Arg Gln

945 950 955 960

Lys Leu Gln Leu Glu Lys Val Thr Thr Glu Ala Lys Leu Lys Lys Leu

965 970 975

Glu Glu Glu Gln Ile Ile Leu Glu Asp Gln Asn Cys Lys Leu Ala Lys

980 985 990

Glu Lys Lys Leu Leu Glu Asp Arg Ile Ala Glu Phe Thr Thr Asn Leu

995 1000 1005

Thr Glu Glu Glu Glu Lys Ser Lys Ser Leu Ala Lys Leu Lys Asn

1010 1015 1020

Lys His Glu Ala Met Ile Thr Asp Leu Glu Glu Arg Leu Arg Arg

1025 1030 1035

Glu Glu Lys Gln Arg Gln Glu Leu Glu Lys Thr Arg Arg Lys Leu

1040 1045 1050

Glu Gly Asp Ser Thr Asp Leu Ser Asp Gln Ile Ala Glu Leu Gln

1055 1060 1065

Ala Gln Ile Ala Glu Leu Lys Met Gln Leu Ala Lys Lys Glu Glu

1070 1075 1080

Glu Leu Gln Ala Ala Leu Ala Arg Val Glu Glu Glu Ala Ala Gln

1085 1090 1095

Lys Asn Met Ala Leu Lys Lys Ile Arg Glu Leu Glu Ser Gln Ile

1100 1105 1110

Ser Glu Leu Gln Glu Asp Leu Glu Ser Glu Arg Ala Ser Arg Asn

1115 1120 1125

Lys Ala Glu Lys Gln Lys Arg Asp Leu Gly Glu Glu Leu Glu Ala

1130 1135 1140

Leu Lys Thr Glu Leu Glu Asp Thr Leu Asp Ser Thr Ala Ala Gln

1145 1150 1155

Gln Glu Leu Arg Ser Lys Arg Glu Gln Glu Val Asn Ile Leu Lys

1160 1165 1170

Lys Thr Leu Glu Glu Glu Ala Lys Thr His Glu Ala Gln Ile Gln

1175 1180 1185

Glu Met Arg Gln Lys His Ser Gln Ala Val Glu Glu Leu Ala Glu

1190 1195 1200

Gln Leu Glu Gln Thr Lys Arg Val Lys Ala Asn Leu Glu Lys Ala

1205 1210 1215

Lys Gln Thr Leu Glu Asn Glu Arg Gly Glu Leu Ala Asn Glu Val

1220 1225 1230

Lys Val Leu Leu Gln Gly Lys Gly Asp Ser Glu His Lys Arg Lys

1235 1240 1245

Lys Val Glu Ala Gln Leu Gln Glu Leu Gln Val Lys Phe Asn Glu

1250 1255 1260

Gly Glu Arg Val Arg Thr Glu Leu Ala Asp Lys Val Thr Lys Leu

1265 1270 1275

Gln Val Glu Leu Asp Asn Val Thr Gly Leu Leu Ser Gln Ser Asp

1280 1285 1290

Ser Lys Ser Ser Lys Leu Thr Lys Asp Phe Ser Ala Leu Glu Ser

1295 1300 1305

Gln Leu Gln Asp Thr Gln Glu Leu Leu Gln Glu Glu Asn Arg Gln

1310 1315 1320

Lys Leu Ser Leu Ser Thr Lys Leu Lys Gln Val Glu Asp Glu Lys

1325 1330 1335

Asn Ser Phe Arg Glu Gln Leu Glu Glu Glu Glu Glu Ala Lys His

1340 1345 1350

Asn Leu Glu Lys Gln Ile Ala Thr Leu His Ala Gln Val Ala Asp

1355 1360 1365

Met Lys Lys Lys Met Glu Asp Ser Val Gly Cys Leu Glu Thr Ala

1370 1375 1380

Glu Glu Val Lys Arg Lys Leu Gln Lys Asp Leu Glu Gly Leu Ser

1385 1390 1395

Gln Arg His Glu Glu Lys Val Ala Ala Tyr Asp Lys Leu Glu Lys

1400 1405 1410

Thr Lys Thr Arg Leu Gln Gln Glu Leu Asp Asp Leu Leu Val Asp

1415 1420 1425

Leu Asp His Gln Arg Gln Ser Ala Cys Asn Leu Glu Lys Lys Gln

1430 1435 1440

Lys Lys Phe Asp Gln Leu Leu Ala Glu Glu Lys Thr Ile Ser Ala

1445 1450 1455

Lys Tyr Ala Glu Glu Arg Asp Arg Ala Glu Ala Glu Ala Arg Glu

1460 1465 1470

Lys Glu Thr Lys Ala Leu Ser Leu Ala Arg Ala Leu Glu Glu Ala

1475 1480 1485

Met Glu Gln Lys Ala Glu Leu Glu Arg Leu Asn Lys Gln Phe Arg

1490 1495 1500

Thr Glu Met Glu Asp Leu Met Ser Ser Lys Asp Asp Val Gly Lys

1505 1510 1515

Ser Val His Glu Leu Glu Lys Ser Lys Arg Ala Leu Glu Gln Gln

1520 1525 1530

Val Glu Glu Met Lys Thr Gln Leu Glu Glu Leu Glu Asp Glu Leu

1535 1540 1545

Gln Ala Thr Glu Asp Ala Lys Leu Arg Leu Glu Val Asn Leu Gln

1550 1555 1560

Ala Met Lys Ala Gln Phe Glu Arg Asp Leu Gln Gly Arg Asp Glu

1565 1570 1575

Gln Ser Glu Glu Lys Lys Lys Gln Leu Val Arg Gln Val Arg Glu

1580 1585 1590

Met Glu Ala Glu Leu Glu Asp Glu Arg Lys Gln Arg Ser Met Ala

1595 1600 1605

Val Ala Ala Arg Lys Lys Leu Glu Met Asp Leu Lys Asp Leu Glu

1610 1615 1620

Ala His Ile Asp Ser Ala Asn Lys Asn Arg Asp Glu Ala Ile Lys

1625 1630 1635

Gln Leu Arg Lys Leu Gln Ala Gln Met Lys Asp Cys Met Arg Glu

1640 1645 1650

Leu Asp Asp Thr Arg Ala Ser Arg Glu Glu Ile Leu Ala Gln Ala

1655 1660 1665

Lys Glu Asn Glu Lys Lys Leu Lys Ser Met Glu Ala Glu Met Ile

1670 1675 1680

Gln Leu Gln Glu Glu Leu Ala Ala Ala Glu Arg Ala Lys Arg Gln

1685 1690 1695

Ala Gln Gln Glu Arg Asp Glu Leu Ala Asp Glu Ile Ala Asn Ser

1700 1705 1710

Ser Gly Lys Gly Ala Leu Ala Leu Glu Glu Lys Arg Arg Leu Glu

1715 1720 1725

Ala Arg Ile Ala Gln Leu Glu Glu Glu Leu Glu Glu Glu Gln Gly

1730 1735 1740

Asn Thr Glu Leu Ile Asn Asp Arg Leu Lys Lys Ala Asn Leu Gln

1745 1750 1755

Ile Asp Gln Ile Asn Thr Asp Leu Asn Leu Glu Arg Ser His Ala

1760 1765 1770

Gln Lys Asn Glu Asn Ala Arg Gln Gln Leu Glu Arg Gln Asn Lys

1775 1780 1785

Glu Leu Lys Val Lys Leu Gln Glu Met Glu Gly Thr Val Lys Ser

1790 1795 1800

Lys Tyr Lys Ala Ser Ile Thr Ala Leu Glu Ala Lys Ile Ala Gln

1805 1810 1815

Leu Glu Glu Gln Leu Asp Asn Glu Thr Lys Glu Arg Gln Ala Ala

1820 1825 1830

Cys Lys Gln Val Arg Arg Thr Glu Lys Lys Leu Lys Asp Val Leu

1835 1840 1845

Leu Gln Val Asp Asp Glu Arg Arg Asn Ala Glu Gln Tyr Lys Asp

1850 1855 1860

Gln Ala Asp Lys Ala Ser Thr Arg Leu Lys Gln Leu Lys Arg Gln

1865 1870 1875

Leu Glu Glu Ala Glu Glu Glu Ala Gln Arg Ala Asn Ala Ser Arg

1880 1885 1890

Arg Lys Leu Gln Arg Glu Leu Glu Asp Ala Thr Glu Thr Ala Asp

1895 1900 1905

Ala Met Asn Arg Glu Val Ser Ser Leu Lys Asn Lys Leu Arg Arg

1910 1915 1920

Gly Asp Leu Pro Phe Val Val Pro Arg Arg Met Ala Arg Lys Gly

1925 1930 1935

Ala Gly Asp Gly Ser Asp Glu Glu Val Asp Gly Lys Ala Asp Gly

1940 1945 1950

Ala Glu Ala Lys Pro Ala Glu

1955 1960

<210>75

<211>152

<212>PRT

<213>人(Homo sapiens)

<400>75

Met Met Cys Asp Phe Thr Glu Asp Gln Thr Thr Glu Phe Lys Glu Ala

1 5 10 15

Phe Gln Leu Phe Asp Arg Thr Gly Asp Gly Lys Ile Leu Tyr Asn Gln

20 25 30

Cys Gly Asp Val Met Arg Pro Leu Gly Gln Asn Pro Thr Asn Thr Glu

35 40 45

Val Val Lys Val Leu Arg Asn Pro Lys Ser Asn Glu Met Asn Val Lys

50 55 60

Leu Leu Asp Phe Glu His Phe Leu Pro Met Leu Gln Met Val Ala Lys

65 70 75 80

Asn Lys Asp Gln Gly Thr Tyr Glu Asp Tyr Val Glu Gly Leu Gln Val

85 90 95

Phe Asp Lys Glu Gly Asn Gly Thr Ile Met Gly Val Glu Phe Trp His

100 105 110

Val Leu Val Thr Leu Gly Glu Lys Ile Thr Glu Glu Glu Val Glu Val

115 120 125

Leu Val Ala Gly Asn Glu Gly Ser Asn Gly Cys Ile Asp Tyr Glu Ala

130 135 140

Phe Val Arg His Ile Leu Ser Gly

145 150

<210>76

<211>524

<212>PRT

<213>人(Homo sapiens)

<400>76

Met Tyr Ala Leu Phe Leu Leu Ala Ser Leu Leu Gly Ala Ala Leu Ala

1 5 10 15

Gly Pro Val Leu Gly Leu Lys Glu Cys Thr Arg Gly Ser Ala Val Trp

20 25 30

Cys Gln Asn Val Lys Thr Ala Ser Asp Cys Gly Ala Val Lys His Cys

35 40 45

Leu Gln Thr Val Trp Asn Lys Pro Thr Val Lys Ser Leu Pro Cys Asp

50 55 60

Ile Cys Lys Asp Val Val Thr Ala Ala Gly Asp Met Leu Lys Asp Asn

65 70 75 80

Ala Thr Glu Glu Glu Ile Leu Val Tyr Leu Glu Lys Thr Cys Asp Trp

85 90 95

Leu Pro Lys Pro Asn Met Ser Ala Ser Cys Lys Glu Ile Val Asp Ser

100 105 110

Tyr Leu Pro Val Ile Leu Asp Ile Ile Lys Gly Glu Met Ser Arg Pro

115 120 125

Gly Glu Val Cys Ser Ala Leu Asn Leu Cys Glu Ser Leu Gln Lys His

130 135 140

Leu Ala Glu Leu Asn His Gln Lys Gln Leu Glu Ser Asn Lys Ile Pro

145 150 155 160

Glu Leu Asp Met Thr Glu Val Val Ala Pro Phe Met Ala Asn Ile Pro

165 170 175

Leu Leu Leu Tyr Pro Gln Asp Gly Pro Arg Ser Lys Pro Gln Pro Lys

180 185 190

Asp Asn Gly Asp Val Cys Gln Asp Cys Ile Gln Met Val Thr Asp Ile

195 200 205

Gln Thr Ala Val Arg Thr Asn Ser Thr Phe Val Gln Ala Leu Val Glu

210 215 220

His Val Lys Glu Glu Cys Asp Arg Leu Gly Pro Gly Met Ala Asp Ile

225 230 235 240

Cys Lys Asn Tyr Ile Ser Gln Tyr Ser Glu Ile Ala Ile Gln Met Met

245 250 255

Met His Met Gln Pro Lys Glu Ile Cys Ala Leu Val Gly Phe Cys Asp

260 265 270

Glu Val Lys Glu Met Pro Met Gln Thr Leu Val Pro Ala Lys Val Ala

275 280 285

Ser Lys Asn Val Ile Pro Ala Leu Glu Leu Val Glu Pro Ile Lys Lys

290 295 300

His Glu Val Pro Ala Lys Ser Asp Val Tyr Cys Glu Val Cys Glu Phe

305 310 315 320

Leu Val Lys Glu Val Thr Lys Leu Ile Asp Asn Asn Lys Thr Glu Lys

325 330 335

Glu Ile Leu Asp Ala Phe Asp Lys Met Cys Ser Lys Leu Pro Lys Ser

340 345 350

Leu Ser Glu Glu Cys Gln Glu Val Val Asp Thr Tyr Gly Ser Ser Ile

355 360 365

Leu Ser Ile Leu Leu Glu Glu Val Ser Pro Glu Leu Val Cys Ser Met

370 375 380

Leu His Leu Cys Ser Gly Thr Arg Leu Pro Ala Leu Thr Val His Val

385 390 395 400

Thr Gln Pro Lys Asp Gly Gly Phe Cys Glu Val Cys Lys Lys Leu Val

405 410 415

Gly Tyr Leu Asp Arg Asn Leu Glu Lys Asn Ser Thr Lys Gln Glu Ile

420 425 430

Leu Ala Ala Leu Glu Lys Gly Cys Ser Phe Leu Pro Asp Pro Tyr Gln

435 440 445

Lys Gln Cys Asp Gln Phe Val Ala Glu Tyr Glu Pro Val Leu Ile Glu

450 455 460

Ile Leu Val Glu Val Met Asp Pro Ser Phe Val Cys Leu Lys Ile Gly

465 470 475 480

Ala Cys Pro Ser Ala His Lys Pro Leu Leu Gly Thr Glu Lys Cys Ile

485 490 495

Trp Gly Pro Ser Tyr Trp Cys Gln Asn Thr Glu Thr Ala Ala Gln Cys

500 505 510

Asn Ala Val Glu His Cys Lys Arg His Val Trp Asn

515 520

<210>77

<211>171

<212>PRT

<213>人(Homo sapiens)

<400>77

Met Ser Ser Lys Arg Thr Lys Thr Lys Thr Lys Lys Arg Pro Gln Arg

1 5 10 15

Ala Thr Ser Asn Val Phe Ala Met Phe Asp Gln Ser Gln Ile Gln Glu

20 25 30

Phe Lys Glu Ala Phe Asn Met Ile Asp Gln Asn Arg Asp Gly Phe Ile

35 40 45

Asp Lys Glu Asp Leu His Asp Met Leu Ala Ser Leu Gly Lys Asn Pro

50 55 60

Thr Asp Glu Tyr Leu Asp Ala Met Met Asn Glu Ala Pro Gly Pro Ile

65 70 75 80

Asn Phe Thr Met Phe Leu Thr Met Phe Gly Glu Lys Leu Asn Gly Thr

85 90 95

Asp Pro Glu Asp Val Ile Arg Asn Ala Phe Ala Cys Phe Asp Glu Glu

100 105 110

Ala Thr Gly Thr Ile Gln Glu Asp Tyr Leu Arg Glu Leu Leu Thr Thr

115 120 125

Met Gly Asp Arg Phe Thr Asp Glu Glu Val Asp Glu Leu Tyr Arg Glu

130 135 140

Ala Pro Ile Asp Lys Lys Gly Asn Phe Asn Tyr Ile Glu Phe Thr Arg

145 150 155 160

Ile Leu Lys His Gly Ala Lys Asp Lys Asp Asp

165 170

<210>78

<211>911

<212>PRT

<213>人(Homo sapiens)

<400>78

Met Glu Glu Leu Gln Asp Asp Tyr Glu Asp Met Met Glu Glu Asn Leu

1 5 10 15

Glu Gln Glu Glu Tyr Glu Asp Pro Asp Ile Pro Glu Ser Gln Met Glu

20 25 30

Glu Pro Ala Ala His Asp Thr Glu Ala Thr Ala Thr Asp Tyr His Thr

35 40 45

Thr Ser His Pro Gly Thr His Lys Val Tyr Val Glu Leu Gln Glu Leu

50 55 60

Val Met Asp Glu Lys Asn Gln Glu Leu Arg Trp Met Glu Ala Ala Arg

65 70 75 80

Trp Val Gln Leu Glu Glu Asn Leu Gly Glu Asn Gly Ala Trp Gly Arg

85 90 95

Pro His Leu Ser His Leu Thr Phe Trp Ser Leu Leu Glu Leu Arg Arg

100 105 110

Val Phe Thr Lys Gly Thr Val Leu Leu Asp Leu Gln Glu Thr Ser Leu

115 120 125

Ala Gly Val Ala Asn Gln Leu Leu Asp Arg Phe Ile Phe Glu Asp Gln

130 135 140

Ile Arg Pro Gln Asp Arg Glu Glu Leu Leu Arg Ala Leu Leu Leu Lys

145 150 155 160

His Ser His Ala Gly Glu Leu Glu Ala Leu Gly Gly Val Lys Pro Ala

165 170 175

Val Leu Thr Arg Ser Gly Asp Pro Ser Gln Pro Leu Leu Pro Gln His

180 185 190

Ser Ser Leu Glu Thr Gln Leu Phe Cys Glu Gln Gly Asp Gly Gly Thr

195 200 205

Glu Gly His Ser Pro Ser Gly Ile Leu Glu Lys Ile Pro Pro Asp Ser

210 215 220

Glu Ala Thr Leu Val Leu Val Gly Arg Ala Asp Phe Leu Glu Gln Pro

225 230 235 240

Val Leu Gly Phe Val Arg Leu Gln Glu Ala Ala Glu Leu Glu Ala Val

245 250 255

Glu Leu Pro Val Pro Ile Arg Phe Leu Phe Val Leu Leu Gly Pro Glu

260 265 270

Ala Pro His Ile Asp Tyr Thr Gln Leu Gly Arg Ala Ala Ala Thr Leu

275 280 285

Met Ser Glu Arg Val Phe Arg Ile Asp Ala Tyr Met Ala Gln Ser Arg

290 295 300

Gly Glu Leu Leu His Ser Leu Glu Gly Phe Leu Asp Cys Ser Leu Val

305 310 315 320

Leu Pro Pro Thr Asp Ala Pro Ser Glu Gln Ala Leu Leu Ser Leu Val

325 330 335

Pro Val Gln Arg Glu Leu Leu Arg Arg Arg Tyr Gln Ser Ser Pro Ala

340 345 350

Lys Pro Asp Ser Ser Phe Tyr Lys Gly Leu Asp Leu Asn Gly Gly Pro

355 360 365

Asp Asp Pro Leu Gln Gln Thr Gly Gln Leu Phe Gly Gly Leu Val Arg

370 375 380

Asp Ile Arg Arg Arg Tyr Pro Tyr Tyr Leu Ser Asp Ile Thr Asp Ala

385 390 395 400

Phe Ser Pro Gln Val Leu Ala Ala Val Ile Phe Ile Tyr Phe Ala Ala

405 410 415

Leu Ser Pro Ala Ile Thr Phe Gly Gly Leu Leu Gly Glu Lys Thr Arg

420 425 430

Asn Gln Met Gly Val Ser Glu Leu Leu Ile Ser Thr Ala Val Gln Gly

435 440 445

Ile Leu Phe Ala Leu Leu Gly Ala Gln Pro Leu Leu Val Val Gly Phe

450 455 460

Ser Gly Pro Leu Leu Val Phe Glu Glu Ala Phe Phe Ser Phe Cys Glu

465 470 475 480

Thr Asn Gly Leu Glu Tyr Ile Val Gly Arg Val Trp Ile Gly Phe Trp

485 490 495

Leu Ile Leu Leu Val Val Leu Val Val Ala Phe Glu Gly Ser Phe Leu

500 505 510

Val Arg Phe Ile Ser Arg Tyr Thr Gln Glu Ile Phe Ser Phe Leu Ile

515 520 525

Ser Leu Ile Phe Ile Tyr Glu Thr Phe Ser Lys Leu Ile Lys Ile Phe

530 535 540

Gln Asp His Pro Leu Gln Lys Thr Tyr Asn Tyr Asn Val Leu Met Val

545 550 555 560

Pro Lys Pro Gln Gly Pro Leu Pro Asn Thr Ala Leu Leu Ser Leu Val

565 570 575

Leu Met Ala Gly Thr Phe Phe Phe Ala Met Met Leu Arg Lys Phe Lys

580 585 590

Asn Ser Ser Tyr Phe Pro Gly Lys Leu Arg Arg Val Ile Gly Asp Phe

595 600 605

Gly Val Pro Ile Ser Ile Leu Ile Met Val Leu Val Asp Phe Phe Ile

610 615 620

Gln Asp Thr Tyr Thr Gln Lys Leu Ser Val Pro Asp Gly Phe Lys Val

625 630 635 640

Ser Asn Ser Ser Ala Arg Gly Trp Val Ile His Pro Leu Gly Leu Arg

645 650 655

Ser Glu Phe Pro Ile Trp Met Met Phe Ala Ser Ala Leu Pro Ala Leu

660 665 670

Leu Val Phe Ile Leu Ile Phe Leu Glu Ser Gln Ile Thr Thr Leu Ile

675 680 685

Val Ser Lys Pro Glu Arg Lys Met Val Lys Gly Ser Gly Phe His Leu

690 695 700

Asp Leu Leu Leu Val Val Gly Met Gly Gly Val Ala Ala Leu Phe Gly

705 710 715 720

Met Pro Trp Leu Ser Ala Thr Thr Val Arg Ser Val Thr His Ala Asn

725 730 735

Ala Leu Thr Val Met Gly Lys Ala Ser Thr Pro Gly Ala Ala Ala Gln

740 745 750

Ile Gln Glu Val Lys Glu Gln Arg Ile Ser Gly Leu Leu Val Ala Val

755 760 765

Leu Val Gly Leu Ser Ile Leu Met Glu Pro Ile Leu Ser Arg Ile Pro

770 775 780

Leu Ala Val Leu Phe Gly Ile Phe Leu Tyr Met Gly Val Thr Ser Leu

785 790 795 800

Ser Gly Ile Gln Leu Phe Asp Arg Ile Leu Leu Leu Phe Lys Pro Pro

805 810 815

Lys Tyr His Pro Asp Val Pro Tyr Val Lys Arg Val Lys Thr Trp Arg

820 825 830

Met His Leu Phe Thr Gly Ile Gln Ile Ile Cys Leu Ala Val Leu Trp

835 840 845

Val Val Lys Ser Thr Pro Ala Ser Leu Ala Leu Pro Phe Val Leu Ile

850 855 860

Leu Thr Val Pro Leu Arg Arg Val Leu Leu Pro Leu Ile Phe Arg Asn

865 870 875 880

Val Glu Leu Gln Cys Leu Asp Ala Asp Asp Ala Lys Ala Thr Phe Asp

885 890 895

Glu Glu Glu Gly Arg Asp Glu Tyr Asp Glu Val Ala Met Pro Val

900 905 910

<210>79

<211>199

<212>PRT

<213>人(Homo sapiens)

<400>79

Met Ala Asn Arg Gly Pro Ala Tyr Gly Leu Ser Arg Glu Val Gln Gln

1 5 10 15

Lys Ile Glu Lys Gln Tyr Asp Ala Asp Leu Glu Gln Ile Leu Ile Gln

20 25 30

Trp Ile Thr Thr Gln Cys Arg Lys Asp Val Gly Arg Pro Gln Pro Gly

35 40 45

Arg Glu Asn Phe Gln Asn Trp Leu Lys Asp Gly Thr Val Leu Cys Glu

50 55 60

Leu Ile Asn Ala Leu Tyr Pro Glu Gly Gln Ala Pro Val Lys Lys Ile

65 70 75 80

Gln Ala Ser Thr Met Ala Phe Lys Gln Met Glu Gln Ile Ser Gln Phe

85 90 95

Leu Gln Ala Ala Glu Arg Tyr Gly Ile Asn Thr Thr Asp Ile Phe Gln

100 105 110

Thr Val Asp Leu Trp Glu Gly Lys Asn Met Ala Cys Val Gln Arg Thr

115 120 125

Leu Met Asn Leu Gly Gly Leu Ala Val Ala Arg Asp Asp Gly Leu Phe

130 135 140

Ser Gly Asp Pro Asn Trp Phe Pro Lys Lys Ser Lys Glu Asn Pro Arg

145 150 155 160

Asn Phe Ser Asp Asn Gln Leu Gln Glu Gly Lys Asn Val Ile Gly Leu

165 170 175

Gln Met Gly Thr Asn Arg Gly Ala Ser Gln Ala Gly Met Thr Gly Tyr

180 185 190

Gly Met Pro Arg Gln Ile Leu

195

<210>80

<211>243

<212>PRT

<213>人(Homo sapiens)

<400>80

Met Met Glu Ala Ile Lys Lys Lys Met Gln Met Leu Lys Leu Asp Lys

1 5 10 15

Glu Asn Ala Leu Asp Arg Ala Glu Gln Ala Glu Ala Glu Gln Lys Gln

20 25 30

Ala Glu Glu Arg Ser Lys Gln Leu Glu Asp Glu Leu Ala Ala Met Gln

35 40 45

Lys Lys Leu Lys Gly Thr Glu Asp Glu Leu Asp Arg Ala Gln Glu Arg

50 55 60

Leu Ala Thr Ala Leu Gln Lys Leu Glu Glu Ala Glu Lys Ala Ala Asp

65 70 75 80

Glu Ser Glu Arg Gly Met Lys Val Ile Glu Asn Arg Ala Leu Lys Asp

85 90 95

Glu Glu Lys Met Glu Leu Gln Glu Ile Gln Leu Lys Glu Ala Lys His

100 105 110

Ile Ala Glu Glu Ala Asp Arg Lys Tyr Glu Glu Val Ala Arg Lys Leu

115 120 l25

Val Ile Ile Glu Gly Asp Leu Glu Arg Thr Glu Glu Arg Ala Glu Leu

130 135 140

Ala Glu Ser Lys Cys Ser Glu Leu Glu Glu Glu Leu Lys Asn Val Thr

145 150 155 160

Asn Asn Leu Lys Ser Leu Glu Ala Gln Ala Glu Lys Tyr Ser Gln Lys

165 170 175

Glu Asp Lys Tyr Glu Glu Glu Ile Lys Ile Leu Thr Asp Lys Leu Lys

180 185 190

Glu Ala Glu Thr Arg Ala Glu Phe Ala Glu Arg Ser Val Ala Lys Leu

195 200 205

Glu Lys Thr Ile Asp Asp Leu Glu Asp Glu Leu Tyr Ala Gln Lys Leu

210 215 220

Lys Tyr Lys Ala Ile Ser Glu Glu Leu Asp His Ala Leu Asn Asp Met

225 230 235 240

Thr Ser Ile

<210>81

<211>2541

<212>PRT

<213>人(Homo sapiens)

<400>81

Met Val Ala Leu Ser Leu Lys Ile Ser Ile Gly Asn Val Val Lys Thr

1 5 10 15

Met Gln Phe Glu Pro Ser Thr Met Val Tyr Asp Ala Cys Arg Ile Ile

20 25 30

Arg Glu Arg Ile Pro Glu Ala Pro Ala Gly Pro Pro Ser Asp Phe Gly

35 40 45

Leu Phe Leu Ser Asp Asp Asp Pro Lys Lys Gly Ile Trp Leu Glu Ala

50 55 60

Gly Lys Ala Leu Asp Tyr Tyr Met Leu Arg Asn Gly Asp Thr Met Glu

65 70 75 80

Tyr Arg Lys Lys Gln Arg Pro Leu Lys Ile Arg Met Leu Asp Gly Thr

85 90 95

Val Lys Thr Ile Met Val Asp Asp Ser Lys Thr Val Thr Asp Met Leu

100 105 110

Met Thr Ile Cys Ala Arg Ile Gly Ile Thr Asn His Asp Glu Tyr Ser

115 120 125

Leu Val Arg Glu Leu Met Glu Glu Lys Lys Glu Glu Ile Thr Gly Thr

130 135 140

Leu Arg Lys Asp Lys Thr Leu Leu Arg Asp Glu Lys Lys Met Glu Lys

145 150 155 160

Leu Lys Gln Lys Leu His Thr Asp Asp Glu Leu Asn Trp Leu Asp His

165 170 175

Gly Arg Thr Leu Arg Glu Gln Gly Val Glu Glu His Glu Thr Leu Leu

180 185 190

Leu Arg Arg Lys Phe Phe Tyr Ser Asp Gln Asn Val Asp Ser Arg Asp

195 200 205

Pro Val Gln Leu Asn Leu Leu Tyr Val Gln Ala Arg Asp Asp Ile Leu

210 215 220

Asn Gly Ser His Pro Val Ser Phe Asp Lys Ala Cys Glu Phe Ala Gly

225 230 235 240

Phe Gln Cys Gln Ile Gln Phe Gly Pro His Asn Glu Gln Lys His Lys

245 250 255

Ala Gly Phe Leu Asp Leu Lys Asp Phe Leu Pro Lys Glu Tyr Val Lys

260 265 270

Gln Lys Gly Glu Arg Lys Ile Phe Gln Ala His Lys Asn Cys Gly Gln

275 280 285

Met Ser Glu Ile Glu Ala Lys Val Arg Tyr Val Lys Leu Ala Arg Ser

290 295 300

Leu Lys Thr Tyr Gly Val Ser Phe Phe Leu Val Lys Glu Lys Met Lys

305 310 315 320

Gly Lys Asn Lys Leu Val Pro Arg Leu Leu Gly Ile Thr Lys Glu Cys

325 330 335

Val Met Arg Val Asp Glu Lys Thr Lys Glu Val Ile Gln Glu Trp Asn

340 345 350

Leu Thr Asn Ile Lys Arg Trp Ala Ala Ser Pro Lys Ser Phe Thr Leu

355 360 365

Asp Phe Gly Asp Tyr Gln Asp Gly Tyr Tyr Ser Val Gln Thr Thr Glu

370 375 380

Gly Glu Gln Ile Ala Gln Leu Ile Ala Gly Tyr Ile Asp Ile Ile Leu

385 390 395 400

Lys Lys Lys Lys Ser Lys Asp His Phe Gly Leu Glu Gly Asp Glu Glu

405 410 415

Ser Thr Met Leu Glu Asp Ser Val Ser Pro Lys Lys Ser Thr Val Leu

420 425 430

Gln Gln Gln Tyr Asn Arg Val Gly Lys Val Glu His Gly Ser Val Ala

435 440 445

Leu Pro Ala Ile Met Arg Ser Gly Ala Ser Gly Pro Glu Asn Phe Gln

450 455 460

Val Gly Ser Met Pro Pro Ala Gln Gln Gln Ile Thr Ser Gly Gln Met

465 470 475 480

His Arg Gly His Met Pro Pro Leu Thr Ser Ala Gln Gln Ala Leu Thr

485 490 495

Gly Thr Ile Asn Ser Ser Met Gln Ala Val Gln Ala Ala Gln Ala Thr

500 505 510

Leu Asp Asp Phe Asp Thr Leu Pro Pro Leu Gly Gln Asp Ala Ala Ser

515 520 525

Lys Ala Trp Arg Lys Asn Lys Met Asp Glu Ser Lys His Glu Ile His

530 535 540

Ser Gln Val Asp Ala Ile Thr Ala Gly Thr Ala Ser Val Val Asn Leu

545 550 555 560

Thr Ala Gly Asp Pro Ala Glu Thr Asp Tyr Thr Ala Val Gly Cys Ala

565 570 575

Val Thr Thr Ile Ser Ser Asn Leu Thr Glu Met Ser Arg Gly Val Lys

580 585 590

Leu Leu Ala Ala Leu Leu Glu Asp Glu Gly Gly Ser Gly Arg Pro Leu

595 600 605

Leu Gln Ala Ala Lys Gly Leu Ala Gly Ala Val Ser Glu Leu Leu Arg

610 615 620

Ser Ala Gln Pro Ala Ser Ala Glu Pro Arg Gln Asn Leu Leu Gln Ala

625 630 635 640

Ala Gly Asn Val Gly Gln Ala Ser Gly Glu Leu Leu Gln Gln Ile Gly

645 650 655

Glu Ser Asp Thr Asp Pro His Phe Gln Asp Ala Leu Met Gln Leu Ala

660 665 670

Lys Ala Val Ala Ser Ala Ala Ala Ala Leu Val Leu Lys Ala Lys Ser

675 680 685

Val Ala Gln Arg Thr Glu Asp Ser Gly Leu Gln Thr Gln Val Ile Ala

690 695 700

Ala Ala Thr Gln Cys Ala Leu Ser Thr Ser Gln Leu Val Ala Cys Thr

705 710 715 720

Lys Val Val Ala Pro Thr Ile Ser Ser Pro Val Cys Gln Glu Gln Leu

725 730 735

Val Glu Ala Gly Arg Leu Val Ala Lys Ala Val Glu Gly Cys Val Ser

740 745 750

Ala Ser Gln Ala Ala Thr Glu Asp Gly Gln Leu Leu Arg Gly Val Gly

755 760 765

Ala Ala Ala Thr Ala Val Thr Gln Ala Leu Asn Glu Leu Leu Gln His

770 775 780

Val Lys Ala His Ala Thr Gly Ala Gly Pro Ala Gly Arg Tyr Asp Gln

785 790 795 800

Ala Thr Asp Thr Ile Leu Thr Val Thr Glu Asn Ile Phe Ser Ser Met

805 810 815

Gly Asp Ala Gly Glu Met Val Gly Gln Ala Arg Ile Leu Ala Gln Ala

820 825 830

Thr Ser Asp Leu Val Asn Ala Ile Lys Ala Asp Ala Glu Gly Glu Ser

835 840 845

Asp Leu Glu Asn Ser Arg Lys Leu Leu Ser Ala Ala Lys Ile Leu Ala

850 855 860

Asp Ala Thr Ala Lys Met Val Glu Ala Ala Lys Gly Ala Ala Ala His

865 870 875 880

Pro Asp Ser Glu Glu Gln Gln Gln Arg Leu Arg Glu Ala Ala Glu Gly

885 890 895

Leu Arg Met Ala Thr Asn Ala Ala Ala Gln Asn Ala Ile Lys Lys Lys

900 905 910

Leu Val Gln Arg Leu Glu His Ala Ala Lys Gln Ala Ala Ala Ser Ala

915 920 925

Thr Gln Thr Ile Ala Ala Ala Gln His Ala Ala Ser Thr Pro Lys Ala

930 935 940

Ser Ala Gly Pro Gln Pro Leu Leu Val Gln Ser Cys Lys Ala Val Ala

945 950 955 960

Glu Gln Ile Pro Leu Leu Val Gln Gly Val Arg Gly Ser Gln Ala Gln

965 970 975

Pro Asp Ser Pro Ser Ala Gln Leu Ala Leu Ile Ala Ala Ser Gln Ser

980 985 990

Phe Leu Gln Pro Gly Gly Lys Met Val Ala Ala Ala Lys Ala Ser Val

995 1000 1005

Pro Thr Ile Gln Asp Gln Ala Ser Ala Met Gln Leu Ser Gln Cys

1010 1015 1020

Ala Lys Asn Leu Gly Thr Ala Leu Ala Glu Leu Arg Thr Ala Ala

1025 1030 1035

Gln Lys Ala Gln Glu Ala Cys Gly Pro Leu Glu Met Asp Ser Ala

1040 1045 1050

Leu Ser Val Val Gln Asn Leu Glu Lys Asp Leu Gln Glu Val Lys

1055 1060 1065

Ala Ala Ala Arg Asp Gly Lys Leu Lys Pro Leu Pro Gly Glu Thr

1070 1075 1080

Met Glu Lys Cys Thr Gln Asp Leu Gly Asn Ser Thr Lys Ala Val

1085 1090 1095

Ser Ser Ala Ile Ala Gln Leu Leu Gly Glu Val Ala Gln Gly Asn

1100 1105 1110

Glu Asn Tyr Ala Gly Ile Ala Ala Arg Asp Val Ala Gly Gly Leu

1115 1120 1125

Arg Ser Leu Ala Gln Ala Ala Arg Gly Val Ala Ala Leu Thr Ser

1130 1135 1140

Asp Pro Ala Val Gln Ala Ile Val Leu Asp Thr Ala Ser Asp Val

1145 1150 1155

Leu Asp Lys Ala Ser Ser Leu Ile Glu Glu Ala Lys Lys Ala Ala

1160 1165 1170

Gly His Pro Gly Asp Pro Glu Ser Gln Gln Arg Leu Ala Gln Val

1175 1180 1185

Ala Lys Ala Val Thr Gln Ala Leu Asn Arg Cys Val Ser Cys Leu

1190 1195 1200

Pro Gly Gln Arg Asp Val Asp Asn Ala Leu Arg Ala Val Gly Asp

1205 1210 1215

Ala Ser Lys Arg Leu Leu Ser Asp Ser Leu Pro Pro Ser Thr Gly

1220 1225 1230

Thr Phe Gln Glu Ala Gln Ser Arg Leu Asn Glu Ala Ala Ala Gly

1235 1240 1245

Leu Asn Gln Ala Ala Thr Glu Leu Val Gln Ala Ser Arg Gly Thr

1250 1255 1260

Pro Gln Asp Leu Ala Arg Ala Ser Gly Arg Phe Gly Gln Asp Phe

1265 1270 1275

Ser Thr Phe Leu Glu Ala Gly Val Glu Met Ala Gly Gln Ala Pro

1280 1285 1290

Ser Gln Glu Asp Arg Ala Gln Val Val Ser Asn Leu Lys Gly Ile

1295 1300 1305

Ser Met Ser Ser Ser Lys Leu Leu Leu Ala Ala Lys Ala Leu Ser

1310 1315 1320

Thr Asp Pro Ala Ala Pro Asn Leu Lys Ser Gln Leu Ala Ala Ala

1325 1330 1335

Ala Arg Ala Val Thr Asp Ser Ile Asn Gln Leu Ile Thr Met Cys

1340 1345 1350

Thr Gln Gln Ala Pro Gly Gln Lys Glu Cys Asp Asn Ala Leu Arg

1355 1360 1365

Glu Leu Glu Thr Val Arg Glu Leu Leu Glu Asn Pro Val Gln Pro

1370 1375 1380

Ile Asn Asp Met Ser Tyr Phe Gly Cys Leu Asp Ser Val Met Glu

1385 1390 1395

Asn Ser Lys Val Leu Gly Glu Ala Met Thr Gly Ile Ser Gln Asn

1400 1405 1410

Ala Lys Asn Gly Asn Leu Pro Glu Phe Gly Asp Ala Ile Ser Thr

1415 1420 1425

Ala Ser Lys Ala Leu Cys Gly Phe Thr Glu Ala Ala Ala Gln Ala

1430 1435 1440

Ala Tyr Leu Val Gly Val Ser Asp Pro Asn Ser Gln Ala Gly Gln

1445 1450 1455

Gln Gly Leu Val Glu Pro Thr Gln Phe Ala Arg Ala Asn Gln Ala

1460 1465 1470

Ile Gln Met Ala Cys Gln Ser Leu Gly Glu Pro Gly Cys Thr Gln

1475 1480 1485

Ala Gln Val Leu Ser Ala Ala Thr Ile Val Ala Lys His Thr Ser

1490 1495 1500

Ala Leu Cys Asn Ser Cys Arg Leu Ala Ser Ala Arg Thr Thr Asn

1505 1510 1515

Pro Thr Ala Lys Arg Gln Phe Val Gln Ser Ala Lys Glu Val Ala

1520 1525 1530

Asn Ser Thr Ala Asn Leu Val Lys Thr Ile Lys Ala Leu Asp Gly

1535 1540 1545

Ala Phe Thr Glu Glu Asn Arg Ala Gln Cys Arg Ala Ala Thr Ala

1550 1555 1560

Pro Leu Leu Glu Ala Val Asp Asn Leu Ser Ala Phe Ala Ser Asn

1565 1570 1575

Pro Glu Phe Ser Ser Ile Pro Ala Gln Ile Ser Pro Glu Gly Arg

1580 1585 1590

Ala Ala Met Glu Pro Ile Val Ile Ser Ala Lys Thr Met Leu Glu

1595 1600 1605

Ser Ala Gly Gly Leu Ile Gln Thr Ala Arg Ala Leu Ala Val Asn

1610 1615 1620

Pro Arg Asp Pro Pro Ser Trp Ser Val Leu Ala Gly His Ser Arg

1625 1630 1635

Thr Val Ser Asp Ser Ile Lys Lys Leu Ile Thr Ser Met Arg Asp

1640 1645 1650

Lys Ala Pro Gly Gln Leu Glu Cys Glu Thr Ala Ile Ala Ala Leu

1655 1660 1665

Asn Ser Cys Leu Arg Asp Leu Asp Gln Ala Ser Leu Ala Ala Val

1670 1675 1680

Ser Gln Gln Leu Ala Pro Arg Glu Gly Ile Ser Gln Glu Ala Leu

1685 1690 1695

His Thr Gln Met Leu Thr Ala Val Gln Glu Ile Ser His Leu Ile

1700 1705 1710

Glu Pro Leu Ala Asn Ala Ala Arg Ala Glu Ala Ser Gln Leu Gly

1715 1720 1725

His Lys Val Ser Gln Met Ala Gln Tyr Phe Glu Pro Leu Thr Leu

1730 1735 1740

Ala Ala Val Gly Ala Ala Ser Lys Thr Leu Ser His Pro Gln Gln

1745 1750 1755

Met Ala Leu Leu Asp Gln Thr Lys Thr Leu Ala Glu Ser Ala Leu

1760 1765 1770

Gln Leu Leu Tyr Thr Ala Lys Glu Ala Gly Gly Asn Pro Lys Gln

1775 1780 1785

Ala Ala His Thr Gln Glu Ala Leu Glu Glu Ala Val Gln Met Met

1790 1795 1800

Thr Glu Ala Val Glu Asp Leu Thr Thr Thr Leu Asn Glu Ala Ala

1805 1810 1815

Ser Ala Ala Gly Val Val Gly Gly Met Val Asp Ser Ile Thr Gln

1820 1825 1830

Ala Ile Asn Gln Leu Asp Glu Gly Pro Met Gly Glu Pro Glu Gly

1835 1840 1845

Ser Phe Val Asp Tyr Gln Thr Thr Met Val Arg Thr Ala Lys Ala

1850 1855 1860

Ile Ala Val Thr Val Gln Glu Met Val Thr Lys Ser Asn Thr Ser

1865 1870 1875

Pro Glu Glu Leu Gly Pro Leu Ala Asn Gln Leu Thr Ser Asp Tyr

1880 1885 1890

Gly Arg Leu Ala Ser Glu Ala Lys Pro Ala Ala Val Ala Ala Glu

1895 1900 1905

Asn Glu Glu Ile Gly Ser His Ile Lys His Arg Val Gln Glu Leu

1910 1915 1920

Gly His Gly Cys Ala Ala Leu Val Thr Lys Ala Gly Ala Leu Gln

1925 1930 1935

Cys Ser Pro Ser Asp Ala Tyr Thr Lys Lys Glu Leu Ile Glu Cys

1940 1945 1950

Ala Arg Arg Val Ser Glu Lys Val Ser His Val Leu Ala Ala Leu

1955 1960 1965

Gln Ala Gly Asn Arg Gly Thr Gln Ala Cys Ile Thr Ala Ala Ser

1970 1975 1980

Ala Val Ser Gly Ile Ile Ala Asp Leu Asp Thr Thr Ile Met Phe

1985 1990 1995

Ala Thr Ala Gly Thr Leu Asn Arg Glu Gly Thr Glu Thr Phe Ala

2000 2005 2010

Asp His Arg Glu Gly Ile Leu Lys Thr Ala Lys Val Leu Val Glu

2015 2020 2025

Asp Thr Lys Val Leu Val Gln Asn Ala Ala Gly Ser Gln Glu Lys

2030 2035 2040

Leu Ala Gln Ala Ala Gln Ser Ser Val Ala Thr Ile Thr Arg Leu

2045 2050 2055

Ala Asp Val Val Lys Leu Gly Ala Ala Ser Leu Gly Ala Glu Asp

2060 2065 2070

Pro Glu Thr Gln Val Val Leu Ile Asn Ala Val Lys Asp Val Ala

2075 2080 2085

Lys Ala Leu Gly Asp Leu Ile Ser Ala Thr Lys Ala Ala Ala Gly

2090 2095 2100

Lys Val Gly Asp Asp Pro Ala Val Trp Gln Leu Lys Asn Ser Ala

2105 2110 2115

Lys Val Met Val Thr Asn Val Thr Ser Leu Leu Lys Thr Val Lys

2120 2125 2130

Ala Val Glu Asp Glu Ala Thr Lys Gly Thr Arg Ala Leu Glu Ala

2135 2140 2145

Thr Thr Glu His Ile Arg Gln Glu Leu Ala Val Phe Cys Ser Pro

2150 2155 2160

Glu Pro Pro Ala Lys Thr Ser Thr Pro Glu Asp Phe Ile Arg Met

2165 2170 2175

Thr Lys Gly Ile Thr Met Ala Thr Ala Lys Ala Val Ala Ala Gly

2180 2185 2190

Asn Ser Cys Arg Gln Glu Asp Val Ile Ala Thr Ala Asn Leu Ser

2195 2200 2205

Arg Arg Ala Ile Ala Asp Met Leu Arg Ala Cys Lys Glu Ala Ala

2210 2215 2220

Tyr His Pro Glu Val Ala Pro Asp Val Arg Leu Arg Ala Leu His

2225 2230 2235

Tyr Gly Arg Glu Cys Ala Asn Gly Tyr Leu Glu Leu Leu Asp His

2240 2245 2250

Val Leu Leu Thr Leu Gln Lys Pro Ser Pro Glu Leu Lys Gln Gln

2255 2260 2265

Leu Thr Gly His Ser Lys Arg Val Ala Gly Ser Val Thr Glu Leu

2270 2275 2280

Ile Gln Ala Ala Glu Ala Met Lys Gly Thr Glu Trp Val Asp Pro

2285 2290 2295

Glu Asp Pro Thr Val Ile Ala Glu Asn Glu Leu Leu Gly Ala Ala

2300 2305 2310

Ala Ala Ile Glu Ala Ala Ala Lys Lys Leu Glu Gln Leu Lys Pro

2315 2320 2325

Arg Ala Lys Pro Lys Glu Ala Asp Glu Ser Leu Asn Phe Glu Glu

2330 2335 2340

Gln Ile Leu Glu Ala Ala Lys Ser Ile Ala Ala Ala Thr Ser Ala

2345 2350 2355

Leu Val Lys Ala Ala Ser Ala Ala Gln Arg Glu Leu Val Ala Gln

2360 2365 2370

Gly Lys Val Gly Ala Ile Pro Ala Asn Ala Leu Asp Asp Gly Gln

2375 2380 2385

Trp Ser Gln Gly Leu Ile Ser Ala Ala Arg Met Val Ala Ala Ala

2390 2395 2400

Thr Asn Asn Leu Cys Glu Ala Ala Asn Ala Ala Val Gln Gly His

2405 2410 2415

Ala Ser Gln Glu Lys Leu Ile Ser Ser Ala Lys Gln Val Ala Ala

2420 2425 2430

Ser Thr Ala Gln Leu Leu Val Ala Cys Lys Val Lys Ala Asp Gln

2435 2440 2445

Asp Ser Glu Ala Met Lys Arg Leu Gln Ala Ala Gly Asn Ala Val

2450 2455 2460

Lys Arg Ala Ser Asp Asn Leu Val Lys Ala Ala Gln Lys Ala Ala

2465 2470 2475

Ala Phe Glu Glu Gln Glu Asn Glu Thr Val Val Val Lys Glu Lys

2480 2485 2490

Met Val Gly Gly Ile Ala Gln Ile Ile Ala Ala Gln Glu Glu Met

2495 2500 2505

Leu Arg Lys Glu Arg Glu Leu Glu Glu Ala Arg Lys Lys Leu Ala

2510 2515 2520

Gln Ile Arg Gln Gln Gln Tyr Lys Phe Leu Pro Ser Glu Leu Arg

2525 2530 2535

Asp Glu His

2540

<210>82

<211>261

<212>PRT

<213>人(Homo sapiens)

<400>82

Met Leu Arg Val Leu Cys Leu Leu Arg Pro Trp Arg Pro Leu Arg Ala

1 5 10 15

Arg Gly Cys Ala Ser Asp Gly Ala Ala Gly Gly Ser Glu Ile Gln Val

20 25 30

Arg Ala Leu Ala Gly Pro Asp Gln Gly Ile Thr Glu Ile Leu Met Asn

35 40 45

Arg Pro Ser Ala Arg Asn Ala Leu Gly Asn Val Phe Val Ser Glu Leu

50 55 60

Leu Glu Thr Leu Ala Gln Leu Arg Glu Asp Arg Gln Val Arg Val Leu

65 70 75 80

Leu Phe Arg Ser Gly Val Lys Gly Ala Phe Cys Ala Gly Ala Asp Leu

85 90 95

Lys Glu Arg Glu Gln Met Ser Glu Ala Glu Val Gly Val Phe Val Gln

100 105 110

Arg Leu Arg Gly Leu Met Asn Asp Ile Ala Ser Ser Ala Val Met Gly

115 120 125

Leu Ile Glu Thr Thr Arg Gly Leu Leu Pro Gly Ala Gly Gly Thr Gln

130 135 140

Arg Leu Pro Arg Cys Leu Gly Val Ala Leu Ala Lys Glu Leu Ile Phe

145 150 155 160

Thr Gly Arg Arg Leu Ser Gly Thr Glu Ala His Val Leu Gly Leu Val

165 170 175

Asn His Ala Val Ala Gln Asn Glu Glu Gly Asp Ala Ala Tyr Gln Arg

180 185 190

Ala Arg Ala Leu Ala Gln Glu Ile Leu Pro Gln Ala Pro Ile Ala Val

195 200 205

Arg Leu Gly Lys Val Ala Ile Asn Arg Gly Thr Glu Val Asp Ile Ala

210 215 220

Ser Gly Met Ala Ile Glu Gly Met Cys Tyr Ala Gln Asn Ile Pro Thr

225 230 235 240

Arg Asp Arg Leu Glu Gly Met Ala Ala Phe Arg Glu Lys Arg Thr Pro

245 250 255

Lys Phe Val Gly Lys

260

<210>83

<211>425

<212>PRT

<213>人(Homo sapiens)

<400>83

Met Asn Tyr Ala Arg Phe Ile Thr Ala Ala Ser Ala Ala Arg Asn Pro

1 5 10 15

Ser Pro Ile Arg Thr Met Thr Asp Ile Leu Ser Arg Gly Pro Lys Ser

20 25 30

Met Ile Ser Leu Ala Gly Gly Leu Pro Asn Pro Asn Met Phe Pro Phe

35 40 45

Lys Thr Ala Val Ile Thr Val Glu Asn Gly Lys Thr Ile Gln Phe Gly

50 55 60

Glu Glu Met Met Lys Arg Ala Leu Gln Tyr Ser Pro Ser Ala Gly Ile

65 70 75 80

Pro Glu Leu Leu Ser Trp Leu Lys Gln Leu Gln Ile Lys Leu His Asn

85 90 95

Pro Pro Thr Ile His Tyr Pro Pro Ser Gln Gly Gln Met Asp Leu Cys

100 105 110

Val Thr Ser Gly Ser Gln Gln Gly Leu Cys Lys Val Phe Glu Met Ile

115 120 125

Ile Asn Pro Gly Asp Asn Val Leu Leu Asp Glu Pro Ala Tyr Ser Gly

130 135 140

Thr Leu Gln Ser Leu His Pro Leu Gly Cys Asn Ile Ile Asn Val Ala

145 150 155 160

Ser Asp Glu Ser Gly Ile Val Pro Asp Ser Leu Arg Asp Ile Leu Ser

165 170 175

Arg Trp Lys Pro Glu Asp Ala Lys Asn Pro Gln Lys Asn Thr Pro Lys

180 185 190

Phe Leu Tyr Thr Val Pro Asn Gly Asn Asn Pro Thr Gly Asn Ser Leu

195 200 205

Thr Ser Glu Arg Lys Lys Glu Ile Tyr Glu Leu Ala Arg Lys Tyr Asp

210 215 220

Phe Leu Ile Ile Glu Asp Asp Pro Tyr Tyr Phe Leu Gln Phe Asn Lys

225 230 235 240

Phe Arg Val Pro Thr Phe Leu Ser Met Asp Val Asp Gly Arg Val Ile

245 250 255

Arg Ala Asp Ser Phe Ser Lys Ile Ile Ser Ser Gly Leu Arg Ile Gly

260 265 270

Phe Leu Thr Gly Pro Lys Pro Leu Ile Glu Arg Val Ile Leu His Ile

275 280 285

Gln Val Ser Thr Leu His Pro Ser Thr Phe Asn Gln Leu Met Ile Ser

290 295 300

Gln Leu Leu His Glu Trp Gly Glu Glu Gly Phe Met Ala His Val Asp

305 310 315 320

Arg Val Ile Asp Phe Tyr Ser Asn Gln Lys Asp Ala Ile Leu Ala Ala

325 330 335

Ala Asp Lys Trp Leu Thr Gly Leu Ala Glu Trp His Val Pro Ala Ala

340 345 350

Gly Met Phe Leu Trp Ile Lys Val Lys Gly Ile Asn Asp Val Lys Glu

355 360 365

Leu Ile Glu Glu Lys Ala Val Lys Met Gly Val Leu Met Leu Pro Gly

370 375 380

Asn Ala Phe Tyr Val Asp Ser Ser Ala Pro Ser Pro Tyr Leu Arg Ala

385 390 395 400

Ser Phe Ser Ser Ala Ser Pro Glu Gln Met Asp Val Ala Phe Gln Val

405 410 415

Leu Ala Gln Leu Ile Lys Glu Ser Leu

420 425

<210>84

<211>698

<212>PRT

<213>人(Homo sapiens)

<400>84

Met Gln Ala His Glu Leu Phe Arg Tyr Phe Arg Met Pro Glu Leu Val

1 5 10 15

Asp Phe Arg Gln Tyr Val Arg Thr Leu Pro Thr Asn Thr Leu Met Gly

20 25 30

Phe Gly Ala Phe Ala Ala Leu Thr Thr Phe Trp Tyr Ala Thr Arg Pro

35 40 45

Lys Pro Leu Lys Pro Pro Cys Asp Leu Ser Met Gln Ser Val Glu Val

50 55 60

Ala Gly Ser Gly Gly Ala Arg Arg Ser Ala Leu Leu Asp Ser Asp Glu

65 70 75 80

Pro Leu Val Tyr Phe Tyr Asp Asp Val Thr Thr Leu Tyr Glu Gly Phe

85 90 95

Gln Arg Gly Ile Gln Val Ser Asn Asn Gly Pro Cys Leu Gly Ser Arg

100 105 110

Lys Pro Asp Gln Pro Tyr Glu Trp Leu Ser Tyr Lys Gln Val Ala Glu

115 120 125

Leu Ser Glu Cys Ile Gly Ser Ala Leu Ile Gln Lys Gly Phe Lys Thr

130 135 140

Ala Pro Asp Gln Phe Ile Gly Ile Phe Ala Gln Asn Arg Pro Glu Trp

145 150 155 160

Val Ile Ile Glu Gln Gly Cys Phe Ala Tyr Ser Met Val Ile Val Pro

165 170 175

Leu Tyr Asp Thr Leu Gly Asn Glu Ala Ile Thr Tyr Ile Val Asn Lys

180 185 190

Ala Glu Leu Ser Leu Val Phe Val Asp Lys Pro Glu Lys Ala Lys Leu

195 200 205

Leu Leu Glu Gly Val Glu Asn Lys Leu Ile Pro Gly Leu Lys Ile Ile

210 215 220

Val Val Met Asp Ala Tyr Gly Ser Glu Leu Val Glu Arg Gly Gln Arg

225 230 235 240

Cys Gly Val Glu Val Thr Ser Met Lys Ala Met Glu Asp Leu Gly Arg

245 250 255

Ala Asn Arg Arg Lys Pro Lys Pro Pro Ala Pro Glu Asp Leu Ala Val

260 265 270

Ile Cys Phe Thr Ser Gly Thr Thr Gly Asn Pro Lys Gly Ala Met Val

275 280 285

Thr His Arg Asn Ile Val Ser Asp Cys Ser Ala Phe Val Lys Ala Thr

290 295 300

Glu Asn Thr Val Asn Pro Cys Pro Asp Asp Thr Leu Ile Ser Phe Leu

305 310 315 320

Pro Leu Ala His Met Phe Glu Arg Val Val Glu Cys Val Met Leu Cys

325 330 335

His Gly Ala Lys Ile Gly Phe Phe Gln Gly Asp Ile Arg Leu Leu Met

340 345 350

Asp Asp Leu Lys Val Leu Gln Pro Thr Val Phe Pro Val Val Pro Arg

355 360 365

Leu Leu Asn Arg Met Phe Asp Arg Ile Phe Gly Gln Ala Asn Thr Thr

370 375 380

Leu Lys Arg Trp Leu Leu Asp Phe Ala Ser Lys Arg Lys Glu Ala Glu

385 390 395 400

Leu Arg Ser Gly Ile Ile Arg Asn Asn Ser Leu Trp Asp Arg Leu Ile

405 410 415

Phe His Lys Val Gln Ser Ser Leu Gly Gly Arg Val Arg Leu Met Val

420 425 430

Thr Gly Ala Ala Pro Val Ser Ala Thr Val Leu Thr Phe Leu Arg Ala

435 440 445

Ala Leu Gly Cys Gln Phe Tyr Glu Gly Tyr Gly Gln Thr Glu Cys Thr

450 455 460

Ala Gly Cys Cys Leu Thr Met Pro Gly Asp Trp Thr Ala Gly His Val

465 470 475 480

Gly Ala Pro Met Pro Cys Asn Leu Ile Lys Leu Val Asp Val Glu Glu

485 490 495

Met Asn Tyr Met Ala Ala Glu Gly Glu Gly Glu Val Cys Val Lys Gly

500 505 510

Pro Asn Val Phe Gln Gly Tyr Leu Lys Asp Pro Ala Lys Thr Ala Glu

515 520 525

Ala Leu Asp Lys Asp Gly Trp Leu His Thr Gly Asp Ile Gly Lys Trp

530 535 540

Leu Pro Asn Gly Thr Leu Lys Ile Ile Asp Arg Lys Lys His Ile Phe

545 550 555 560

Lys Leu Ala Gln Gly Glu Tyr Ile Ala Pro Glu Lys Ile Glu Asn Ile

565 570 575

Tyr Met Arg Ser Glu Pro Val Ala Gln Val Phe Val His Gly Glu Ser

580 585 590

Leu Gln Ala Phe Leu Ile Ala Ile Val Val Pro Asp Val Glu Thr Leu

595 600 605

Cys Ser Trp Ala Gln Lys Arg Gly Phe Glu Gly Ser Phe Glu Glu Leu

610 615 620

Cys Arg Asn Lys Asp Val Lys Lys Ala Ile Leu Glu Asp Met Val Arg

625 630 635 640

Leu Gly Lys Asp Ser Gly Leu Lys Pro Phe Glu Gln Val Lys Gly Ile

645 650 655

Thr Leu His Pro Glu Leu Phe Ser Ile Asp Asn Gly Leu Leu Thr Pro

660 665 670

Thr Met Lys Ala Lys Arg Pro Glu Leu Arg Asn Tyr Phe Arg Ser Gln

675 680 685

Ile Asp Asp Leu Tyr Ser Thr Ile Lys Val

690 695

<210>85

<211>902

<212>PRT

<213>人(Homo sapiens)

<400>85

Met Lys Ile Ala Val Ile Gly Gln Ser Leu Phe Gly Gln Glu Val Tyr

1 5 10 15

Cys His Leu Arg Lys Glu Gly His Glu Val Val Gly Val Phe Thr Val

20 25 30

Pro Asp Lys Asp Gly Lys Ala Asp Pro Leu Gly Leu Glu Ala Glu Lys

35 40 45

Asp Gly Val Pro Val Phe Lys Tyr Ser Arg Trp Arg Ala Lys Gly Gln

50 55 60

Ala Leu Pro Asp Val Val Ala Lys Tyr Gln Ala Leu Gly Ala Glu Leu

65 70 75 80

Asn Val Leu Pro Phe Cys Ser Gln Phe Ile Pro Met Glu Ile Ile Ser

85 90 95

Ala Pro Arg His Gly Ser Ile Ile Tyr His Pro Ser Leu Leu Pro Arg

100 105 110

His Arg Gly Ala Ser Ala Ile Asn Trp Thr Leu Ile His Gly Asp Lys

115 120 125

Lys Gly Gly Phe Ser Ile Phe Trp Ala Asp Asp Gly Leu Asp Thr Gly

130 135 140

Asp Leu Leu Leu Gln Lys Glu Cys Glu Val Leu Pro Asp Asp Thr Val

145 150 155 160

Ser Thr Leu Tyr Asn Arg Phe Leu Phe Pro Glu Gly Ile Lys Gly Met

165 170 175

Val Gln Ala Val Arg Leu Ile Ala Glu Gly Lys Ala Pro Arg Leu Pro

180 185 190

Gln Pro Glu Glu Gly Ala Thr Tyr Glu Gly Ile Gln Lys Lys Glu Thr

195 200 205

Ala Lys Ile Asn Trp Asp Gln Pro Ala Glu Ala Ile His Asn Trp Ile

210 215 220

Arg Gly Asn Asp Lys Val Pro Gly Ala Trp Thr Glu Ala Cys Glu Gln

225 230 235 240

Lys Leu Thr Phe Phe Asn Ser Thr Leu Asn Thr Ser Gly Leu Val Pro

245 250 255

Glu Gly Asp Ala Leu Pro Ile Pro Gly Ala His Arg Pro Gly Val Val

260 265 270

Thr Lys Ala Gly Leu Ile Leu Phe Gly Asn Asp Asp Lys Met Leu Leu

275 280 285

Val Lys Asn Ile Gln Leu Glu Asp Gly Lys Met Ile Leu Ala Ser Asn

290 295 300

Phe Phe Lys Gly Ala Ala Ser Ser Val Leu Glu Leu Thr Glu Ala Glu

305 310 315 320

Leu Val Thr Ala Glu Ala Val Arg Ser Val Trp Gln Arg Ile Leu Pro

325 330 335

Lys Val Leu Glu Val Glu Asp Ser Thr Asp Phe Phe Lys Ser Gly Ala

340 345 350

Ala Ser Val Asp Val Val Arg Leu Val Glu Glu Val Lys Glu Leu Cys

355 360 365

Asp Gly Leu Glu Leu Glu Asn Glu Asp Val Tyr Met Ala Ser Thr Phe

370 375 380

Gly Asp Phe Ile Gln Leu Leu Val Arg Lys Leu Arg Gly Asp Asp Glu

385 390 395 400

Glu Gly Glu Cys Ser Ile Asp Tyr Val Glu Met Ala Val Asn Lys Arg

405 410 415

Thr Val Arg Met Pro His Gln Leu Phe Ile Gly Gly Glu Phe Val Asp

420 425 430

Ala Glu Gly Ala Lys Thr Ser Glu Thr Ile Asn Pro Thr Asp Gly Ser

435 440 445

Val Ile Cys Gln Val Ser Leu Ala Gln Val Thr Asp Val Asp Lys Ala

450 455 460

Val Ala Ala Ala Lys Asp Ala Phe Glu Asn Gly Arg Trp Gly Lys Ile

465 470 475 480

Ser Ala Arg Asp Arg Gly Arg Leu Met Tyr Arg Leu Ala Asp Leu Met

485 490 495

Glu Gln His Gln Glu Glu Leu Ala Thr Ile Glu Ala Leu Asp Ala Gly

500 505 510

Ala Val Tyr Thr Leu Ala Leu Lys Thr His Val Gly Met Ser Ile Gln

515 520 525

Thr Phe Arg Tyr Phe Ala Gly Trp Cys Asp Lys Ile Gln Gly Ser Thr

530 535 540

Ile Pro Ile Asn Gln Ala Arg Pro Asn Arg Asn Leu Thr Leu Thr Arg

545 550 555 560

Lys Glu Pro Val Gly Val Cys Gly Ile Ile Ile Pro Trp Asn Tyr Pro

565 570 575

Leu Met Met Leu Ser Trp Lys Thr Ala Ala Cys Leu Ala Ala Gly Asn

580 585 590

Thr Val Val Ile Lys Pro Ala Gln Val Thr Pro Leu Thr Ala Leu Lys

595 600 605

Phe Ala Glu Leu Thr Leu Lys Ala Gly Ile Pro Lys Gly Val Val Asn

610 615 620

Val Leu Pro Gly Ser Gly Ser Leu Val Gly Gln Arg Leu Ser Asp His

625 630 635 640

Pro Asp Val Arg Lys Ile Gly Phe Thr Gly Ser Thr Glu Val Gly Lys

645 650 655

His Ile Met Lys Ser Cys Ala Ile Ser Asn Val Lys Lys Val Ser Leu

660 665 670

Glu Leu Gly Gly Lys Ser Pro Leu Ile Ile Phe Ala Asp Cys Asp Leu

675 680 685

Asn Lys Ala Val Gln Met Gly Met Ser Ser Val Phe Phe Asn Lys Gly

690 695 700

Glu Asn Cys Ile Ala Ala Gly Arg Leu Phe Val Glu Asp Ser Ile His

705 710 715 720

Asp Glu Phe Val Arg Arg Val Val Glu Glu Val Arg Lys Met Lys Val

725 730 735

Gly Asn Pro Leu Asp Arg Asp Thr Asp His Gly Pro Gln Asn His His

740 745 750

Ala His Leu Val Lys Leu Met Glu Tyr Cys Gln His Gly Val Lys Glu

755 760 765

Gly Ala Thr Leu Val Cys Gly Gly Asn Gln Val Pro Arg Pro Gly Phe

770 775 780

Phe Phe Glu Pro Thr Val Phe Thr Asp Val Glu Asp His Met Phe Ile

785 790 795 800

Ala Lys Glu Glu Ser Phe Gly Pro Val Met Ile Ile Ser Arg Phe Ala

805 810 815

Asp Gly Asp Leu Asp Ala Val Leu Ser Arg Ala Asn Ala Thr Glu Phe

820 825 830

Gly Leu Ala Ser Gly Val Phe Thr Arg Asp Ile Asn Lys Ala Leu Tyr

835 840 845

Val Ser Asp Lys Leu Gln Ala Gly Thr Val Phe Val Asn Thr Tyr Asn

850 855 860

Lys Thr Asp Val Ala Ala Pro Phe Gly Gly Phe Lys Gln Ser Gly Phe

865 870 875 880

Gly Lys Asp Leu Gly Glu Ala Ala Leu Asn Glu Tyr Leu Arg Val Lys

885 890 895

Thr Val Thr Phe Glu Tyr

900

<210>86

<211>412

<212>PRT

<213>人(Homo sapiens)

<400>86

Met Ser Ser Lys Gly Ser Val Val Leu Ala Tyr Ser Gly Gly Leu Asp

1 5 10 15

Thr Ser Cys Ile Leu Val Trp Leu Lys Glu Gln Gly Tyr Asp Val Ile

20 25 30

Ala Tyr Leu Ala Asn Ile Gly Gln Lys Glu Asp Phe Glu Glu Ala Arg

35 40 45

Lys Lys Ala Leu Lys Leu Gly Ala Lys Lys Val Phe Ile Glu Asp Val

50 55 60

Ser Arg Glu Phe Val Glu Glu Phe Ile Trp Pro Ala Ile Gln Ser Ser

65 70 75 80

Ala Leu Tyr Glu Asp Arg Tyr Leu Leu Gly Thr Ser Leu Ala Arg Pro

85 90 95

Cys Ile Ala Arg Lys Gln Val Glu Ile Ala Gln Arg Glu Gly Ala Lys

100 105 110

Tyr Val Ser His Gly Ala Thr Gly Lys Gly Asn Asp Gln Val Arg Phe

115 120 125

Glu Leu Ser Cys Tyr Ser Leu Ala Pro Gln Ile Lys Val Ile Ala Pro

130 135 140

Trp Arg Met Pro Glu Phe Tyr Asn Arg Phe Lys Gly Arg Asn Asp Leu

145 150 155 160

Met Glu Tyr Ala Lys Gln His Gly Ile Pro Ile Pro Val Thr Pro Lys

165 170 175

Asn Pro Trp Ser Met Asp Glu Asn Leu Met His Ile Ser Tyr Glu Ala

180 185 190

Gly Ile Leu Glu Asn Pro Lys Asn Gln Ala Pro Pro Gly Leu Tyr Thr

195 200 205

Lys Thr Gln Asp Pro Ala Lys Ala Pro Asn Thr Pro Asp Ile Leu Glu

210 215 220

Ile Glu Phe Lys Lys Gly Val Pro Val Lys Val Thr Asn Val Lys Asp

225 230 235 240

Gly Thr Thr His Gln Thr Ser Leu Glu Leu Phe Met Tyr Leu Asn Glu

245 250 255

Val Ala Gly Lys His Gly Val Gly Arg Ile Asp Ile Val Glu Asn Arg

260 265 270

Phe Ile Gly Met Lys Ser Arg Gly Ile Tyr Glu Thr Pro Ala Gly Thr

275 280 285

Ile Leu Tyr His Ala His Leu Asp Ile Glu Ala Phe Thr Met Asp Arg

290 295 300

Glu Val Arg Lys Ile Lys Gln Gly Leu Gly Leu Lys Phe Ala Glu Leu

305 310 315 320

Val Tyr Thr Gly Phe Trp His Ser Pro Glu Cys Glu Phe Val Arg His

325 330 335

Cys Ile Ala Lys Ser Gln Glu Arg Val Glu Gly Lys Val Gln Val Ser

340 345 350

Val Leu Lys Gly Gln Val Tyr Ile Leu Gly Arg Glu Ser Pro Leu Ser

355 360 365

Leu Tyr Asn Glu Glu Leu Val Ser Met Asn Val Gln Gly Asp Tyr Glu

370 375 380

Pro Thr Asp Ala Thr Gly Phe Ile Asn Ile Asn Ser Leu Arg Leu Lys

385 390 395 400

Glu Tyr His Arg Leu Gln Ser Lys Val Thr Ala Lys

405 410

<210>87

<211>866

<212>PRT

<213>人(Homo sapiens)

<400>87

Met Leu Arg Pro Gly Ala Gln Leu Leu Arg Gly Leu Leu Leu Arg Ser

1 5 10 15

Cys Pro Leu Gln Gly Ser Pro Gly Arg Pro Arg Ser Val Cys Gly Arg

20 25 30

Glu Gly Glu Glu Lys Pro Pro Leu Ser Ala Glu Thr Gln Trp Lys Asp

35 40 45

Arg Ala Glu Thr Val Ile Ile Gly Gly Gly Cys Val Gly Val Ser Leu

50 55 60

Ala Tyr His Leu Ala Lys Ala Gly Met Lys Asp Val Val Leu Leu Glu

65 70 75 80

Lys Ser Glu Leu Thr Ala Gly Ser Thr Trp His Ala Ala Gly Leu Thr

85 90 95

Thr Tyr Phe His Pro Gly Ile Asn Leu Lys Lys Ile His Tyr Asp Ser

100 105 110

Ile Lys Leu Tyr Glu Lys Leu Glu Glu Glu Thr Gly Gln Val Val Gly

115 120 125

Phe His Gln Pro Gly Ser Ile Arg Leu Ala Thr Thr Pro Val Arg Val

130 135 140

Asp Glu Phe Lys Tyr Gln Met Thr Arg Thr Gly Trp His Ala Thr Glu

145 150 155 160

Gln Tyr Leu Ile Glu Pro Glu Lys Ile Gln Glu Met Phe Pro Leu Leu

165 170 175

Asn Met Asn Lys Val Leu Ala Gly Leu Tyr Asn Pro Gly Asp Gly His

180 185 190

Ile Asp Pro Tyr Ser Leu Thr Met Ala Leu Ala Ala Gly Ala Arg Lys

195 200 205

Cys Gly Ala Leu Leu Lys Tyr Pro Ala Pro Val Thr Ser Leu Lys Ala

210 215 220

Arg Ser Asp Gly Thr Trp Asp Val Glu Thr Pro Gln Gly Ser Met Arg

225 230 235 240

Ala Asn Arg Ile Val Asn Ala Ala Gly Phe Trp Ala Arg Glu Val Gly

245 250 255

Lys Met Ile Gly Leu Glu His Pro Leu Ile Pro Val Gln His Gln Tyr

260 265 270

Val Val Thr Ser Thr Ile Ser Glu Val Lys Ala Leu Lys Arg Glu Leu

275 280 285

Pro Val Leu Arg Asp Leu Glu Gly Ser Tyr Tyr Leu Arg Gln Glu Arg

290 295 300

Asp Gly Leu Leu Phe Gly Pro Tyr Glu Ser Gln Glu Lys Met Lys Val

305 310 315 320

Gln Asp Ser Trp Val Thr Asn Gly Val Pro Pro Gly Phe Gly Lys Glu

325 330 335

Leu Phe Glu Ser Asp Leu Asp Arg Ile Met Glu His Ile Lys Ala Ala

340 345 350

Met Glu Met Val Pro Val Leu Lys Lys Ala Asp Ile Ile Asn Val Val

355 360 365

Asn Gly Pro Ile Thr Tyr Ser Pro Asp Ile Leu Pro Met Val Gly Pro

370 375 380

His Gln Gly Val Arg Asn Tyr Trp Val Ala Ile Gly Phe Gly Tyr Gly

385 390 395 400

Ile Ile His Ala Gly Gly Val Gly Lys Tyr Leu Ser Asp Trp Ile Leu

405 410 415

His Gly Glu Pro Pro Phe Asp Leu Ile Glu Leu Asp Pro Asn Arg Tyr

420 425 430

Gly Lys Trp Thr Thr Thr Gln Tyr Thr Glu Ala Lys Ala Arg Glu Ser

435 440 445

Tyr Gly Phe Asn Asn Ile Val Gly Tyr Pro Lys Glu Glu Arg Phe Ala

450 455 460

Gly Arg Pro Thr Gln Arg Val Ser Gly Leu Tyr Gln Arg Leu Glu Ser

465 470 475 480

Lys Cys Ser Met Gly Phe His Ala Gly Trp Glu Gln Pro His Trp Phe

485 490 495

Tyr Lys Pro Gly Gln Asp Thr Gln Tyr Arg Pro Ser Phe Arg Arg Thr

500 505 510

Asn Trp Phe Glu Pro Val Gly Ser Glu Tyr Lys Gln Val Met Gln Arg

515 520 525

Val Ala Val Thr Asp Leu Ser Pro Phe Gly Lys Phe Asn Ile Lys Gly

530 535 540

Gln Asp Ser Ile Arg Leu Leu Asp His Leu Phe Ala Asn Val Ile Pro

545 550 555 560

Lys Val Gly Phe Thr Asn Ile Ser His Met Leu Thr Pro Lys Gly Arg

565 570 575

Val Tyr Ala Glu Leu Thr Val Ser His Gln Ser Pro Gly Glu Phe Leu

580 585 590

Leu Ile Thr Gly Ser Gly Ser Glu Leu His Asp Leu Arg Trp Ile Glu

595 600 605

Glu Glu Ala Val Lys Gly Gly Tyr Asp Val Glu Ile Lys Asn Ile Thr

610 615 620

Asp Glu Leu Gly Val Leu Gly Val Ala Gly Pro Gln Ala Arg Lys Val

625 630 635 640

Leu Gln Lys Leu Thr Ser Glu Asp Leu Ser Asp Asp Val Phe Lys Phe

645 650 655

Leu Gln Thr Lys Ser Leu Lys Val Ser Asn Ile Pro Val Thr Ala Ile

660 665 670

Arg Ile Ser Tyr Thr Gly Glu Leu Gly Trp Glu Leu Tyr His Arg Arg

675 680 685

Glu Asp Ser Val Ala Leu Tyr Asp Ala Ile Met Asn Ala Gly Gln Glu

690 695 700

Glu Gly Ile Asp Asn Phe Gly Thr Tyr Ala Met Asn Ala Leu Arg Leu

705 710 715 720

Glu Lys Ala Phe Arg Ala Trp Gly Leu Glu Met Asn Cys Asp Thr Asn

725 730 735

Pro Leu Glu Ala Gly Leu Glu Tyr Phe Val Lys Leu Asn Lys Pro Ala

740 745 750

Asp Phe Ile Gly Lys Gln Ala Leu Lys Gln Ile Lys Ala Lys Gly Leu

755 760 765

Lys Arg Arg Leu Val Cys Leu Thr Leu Ala Thr Asp Asp Val Asp Pro

770 775 780

Glu Gly Asn Glu Ser Ile Trp Tyr Asn Gly Lys Val Val Gly Asn Thr

785 790 795 800

Thr Ser Gly Ser Tyr Ser Tyr Ser Ile Gln Lys Ser Leu Ala Phe Ala

805 810 815

Tyr Val Pro Val Gln Leu Ser Glu Val Gly Gln Gln Val Glu Val Glu

820 825 830

Leu Leu Gly Lys Asn Tyr Pro Ala Val Ile Ile Gln Glu Pro Leu Val

835 840 845

Leu Thr Glu Pro Thr Arg Asn Arg Leu Gln Lys Lys Gly Gly Lys Asp

850 855 860

Lys Thr

865

<210>88

<211>519

<212>PRT

<213>人(Homo sapiens)

<400>88

Met Ala Ala Pro Ser Arg Leu Leu Ile Arg Gly Gly Arg Val Val Asn

1 5 10 15

Asp Asp Phe Ser Glu Val Ala Asp Val Leu Val Glu Asp Gly Val Val

20 25 30

Arg Ala Leu Gly His Asp Leu Leu Pro Pro Gly Gly Ala Pro Ala Gly

35 40 45

Leu Arg Val Leu Asp Ala Ala Gly Lys Leu Val Leu Pro Gly Gly Ile

50 55 60

Asp Thr His Thr His Met Gln Phe Pro Phe Met Gly Ser Arg Ser Ile

65 70 75 80

Asp Asp Phe His Gln Gly Thr Lys Ala Ala Leu Ser Gly Gly Thr Thr

85 90 95

Met Ile Ile Asp Phe Ala Ile Pro Gln Lys Gly Gly Ser Leu Ile Glu

100 105 110

Ala Phe Glu Thr Trp Arg Ser Trp Ala Asp Pro Lys Val Cys Cys Asp

115 120 125

Tyr Ser Leu His Val Ala Val Thr Trp Trp Ser Asp Gln Val Lys Glu

130 135 140

Glu Met Lys Ile Leu Val Gln Asp Lys Gly Val Asn Ser Phe Lys Met

145 150 155 160

Phe Met Ala Tyr Lys Asp Leu Tyr Met Val Thr Asp Leu Glu Leu Tyr

165 170 175

Glu Ala Phe Ser Arg Cys Lys Glu Ile Gly Ala Ile Ala Gln Val His

180 185 190

Ala Glu Asn Gly Asp Leu Ile Ala Glu Gly Ala Lys Lys Met Leu Ala

195 200 205

Leu Gly Ile Thr Gly Pro Glu Gly His Glu Leu Cys Arg Pro Glu Ala

210 215 220

Val Glu Ala Glu Ala Thr Leu Arg Ala Ile Thr Ile Ala Ser Ala Val

225 230 235 240

Asn Cys Pro Leu Tyr Ile Val His Val Met Ser Lys Ser Ala Ala Lys

245 250 255

Val Ile Ala Asp Ala Arg Arg Asp Gly Lys Val Val Tyr Gly Glu Pro

260 265 270

Ile Ala Ala Ser Leu Gly Thr Asp Gly Thr His Tyr Trp Asn Lys Glu

275 280 285

Trp His His Ala Ala His His Val Met Gly Pro Pro Leu Arg Pro Asp

290 295 300

Pro Ser Thr Pro Asp Phe Leu Met Asn Leu Leu Ala Asn Asp Asp Leu

305 310 315 320

Thr Thr Thr Gly Thr Asp Asn Cys Thr Phe Asn Thr Cys Gln Lys Ala

325 330 335

Leu Gly Lys Asp Asp Phe Thr Lys Ile Pro Asn Gly Val Asn Gly Val

340 345 350

Glu Asp Arg Met Ser Val Ile Trp Glu Lys Gly Val His Ser Gly Lys

355 360 365

Met Asp Glu Asn Arg Phe Val Ala Val Thr Ser Thr Asn Ala Ala Lys

370 375 380

Ile Phe Asn Leu Tyr Pro Arg Lys Gly Arg Ile Ala Val Gly Ser Asp

385 390 395 400

Ala Asp Ile Val Ile Trp Asp Pro Lys Gly Thr Arg Thr Ile Ser Ala

405 410 415

Lys Thr His His Gln Ala Val Asn Phe Asn Ile Phe Glu Gly Met Val

420 425 430

Cys His Gly Val Pro Leu Val Thr Ile Ser Arg Gly Lys Val Val Tyr

435 440 445

Glu Ala Gly Val Phe Ser Val Thr Ala Gly Asp Gly Lys Phe Ile Pro

450 455 460

Arg Lys Pro Phe Ala Glu Tyr Ile Tyr Lys Arg Ile Lys Gln Arg Asp

465 470 475 480

Arg Thr Cys Thr Pro Thr Pro Val Glu Arg Ala Pro Tyr Lys Gly Glu

485 490 495

Val Ala Thr Leu Lys Ser Arg Val Thr Lys Glu Asp Ala Thr Ala Gly

500 505 510

Thr Arg Lys Gln Ala His Pro

515

<210>89

<211>915

<212>PRT

<213>人(Homo sapiens)

<400>89

Met Ala Arg Arg Ser Ser Phe Gln Ser Cys Gln Ile Ile Ser Leu Phe

1 5 10 15

Thr Phe Ala Val Gly Val Ser Ile Cys Leu Gly Phe Thr Ala His Arg

20 25 30

Ile Lys Arg Ala Glu Gly Trp Glu Glu Gly Pro Pro Thr Val Leu Ser

35 40 45

Asp Ser Pro Trp Thr Asn Ile Ser Gly Ser Cys Lys Gly Arg Cys Phe

50 55 60

Glu Leu Gln Glu Ala Gly Pro Pro Asp Cys Arg Cys Asp Asn Leu Cys

65 70 75 80

Lys Ser Tyr Thr Ser Cys Cys His Asp Phe Asp Glu Leu Cys Leu Lys

85 90 95

Thr Ala Arg Gly Trp Glu Cys Thr Lys Asp Arg Cys Gly Glu Val Arg

100 105 110

Asn Glu Glu Asn Ala Cys His Cys Ser Glu Asp Cys Leu Ala Arg Gly

115 120 125

Asp Cys Cys Thr Asn Tyr Gln Val Val Cys Lys Gly Glu Ser His Trp

130 135 140

Val Asp Asp Asp Cys Glu Glu Ile Lys Ala Ala Glu Cys Pro Ala Gly

145 150 155 160

Phe Val Arg Pro Pro Leu Ile Ile Phe Ser Val Asp Gly Phe Arg Ala

165 170 175

Ser Tyr Met Lys Lys Gly Ser Lys Val Met Pro Asn Ile Glu Lys Leu

180 185 190

Arg Ser Cys Gly Thr His Ser Pro Tyr Met Arg Pro Val Tyr Pro Thr

195 200 205

Lys Thr Phe Pro Asn Leu Tyr Thr Leu Ala Thr Gly Leu Tyr Pro Glu

210 215 220

Ser His Gly Ile Val Gly Asn Ser Met Tyr Asp Pro Val Phe Asp Ala

225 230 235 240

Thr Phe His Leu Arg Gly Arg Glu Lys Phe Asn His Arg Trp Trp Gly

245 250 255

Gly Gln Pro Leu Trp Ile Thr Ala Thr Lys Gln Gly Val Lys Ala Gly

260 265 270

Thr Phe Phe Trp Ser Val Val Ile Pro His Glu Arg Arg Ile Leu Thr

275 280 285

Ile Leu Arg Trp Leu Thr Leu Pro Asp His Glu Arg Pro Ser Val Tyr

290 295 300

Ala Phe Tyr Ser Glu Gln Pro Asp Phe Ser Gly His Lys Tyr Gly Pro

305 310 315 320

Phe Gly Pro Glu Glu Ser Ser Tyr Gly Ser Pro Phe Thr Pro Ala Lys

325 330 335

Arg Pro Lys Arg Lys Val Ala Pro Lys Arg Arg Gln Glu Arg Pro Val

340 345 350

Ala Pro Pro Lys Lys Arg Arg Arg Lys Ile His Arg Met Asp His Tyr

355 360 365

Ala Ala Glu Thr Arg Gln Asp Lys Met Thr Asn Pro Leu Arg Glu Ile

370 375 380

Asp Lys Ile Val Gly Gln Leu Met Asp Gly Leu Lys Gln Leu Lys Leu

385 390 395 400

Arg Arg Cys Val Asn Val Ile Phe Val Gly Asp His Gly Met Glu Asp

405 410 415

Val Thr Cys Asp Arg Thr Glu Phe Leu Ser Asn Tyr Leu Thr Asn Val

420 425 430

Asp Asp Ile Thr Leu Val Pro Gly Thr Leu Gly Arg Ile Arg Ser Lys

435 440 445

Phe Ser Asn Asn Ala Lys Tyr Asp Pro Lys Ala Ile Ile Ala Asn Leu

450 455 460

Thr Cys Lys Lys Pro Asp Gln His Phe Lys Pro Tyr Leu Lys Gln His

465 470 475 480

Leu Pro Lys Arg Leu His Tyr Ala Asn Asn Arg Arg Ile Glu Asp Ile

485 490 495

His Leu Leu Val Glu Arg Arg Trp His Val Ala Arg Lys Pro Leu Asp

500 505 510

Val Tyr Lys Lys Pro Ser Gly Lys Cys Phe Phe Gln Gly Asp His Gly

515 520 525

Phe Asp Asn Lys Val Asn Ser Met Gln Thr Val Phe Val Gly Tyr Gly

530 535 540

Pro Thr Phe Lys Tyr Lys Thr Lys Val Pro Pro Phe Glu Asn Ile Glu

545 550 555 560

Leu Tyr Asn Val Met Cys Asp Leu Leu Gly Leu Lys Pro Ala Pro Asn

565 570 575

Asn Gly Thr His Gly Ser Leu Asn His Leu Leu Arg Thr Asn Thr Phe

580 585 590

Arg Pro Thr Met Pro Glu Glu Val Thr Arg Pro Asn Tyr Pro Gly Ile

595 600 605

Met Tyr Leu Gln Ser Asp Phe Asp Leu Gly Cys Thr Cys Asp Asp Lys

610 615 620

Val Glu Pro Lys Asn Lys Leu Asp Glu Leu Asn Lys Arg Leu His Thr

625 630 635 640

Lys Gly Ser Thr Glu Glu Arg His Leu Leu Tyr Gly Arg Pro Ala Val

645 650 655

Leu Tyr Arg Thr Arg Tyr Asp Ile Leu Tyr His Thr Asp Phe Glu Ser

660 665 670

Gly Tyr Ser Glu Ile Phe Leu Met Leu Leu Trp Thr Ser Tyr Thr Val

675 680 685

Ser Lys Gln Ala Glu Val Ser Ser Val Pro Asp His Leu Thr Ser Cys

690 695 700

Val Arg Pro Asp Val Arg Val Ser Pro Ser Phe Ser Gln Asn Cys Leu

705 710 715 720

Ala Tyr Lys Asn Asp Lys Gln Met Ser Tyr Gly Phe Leu Phe Pro Pro

725 730 735

Tyr Leu Ser Ser Ser Pro Glu Ala Lys Tyr Asp Ala Phe Leu Val Thr

740 745 750

Asn Met Val Pro Met Tyr Pro Ala Phe Lys Arg Val Trp Asn Tyr Phe

755 760 765

Gln Arg Val Leu Val Lys Lys Tyr Ala Ser Glu Arg Asn Gly Val Asn

770 775 780

Val Ile Ser Gly Pro Ile Phe Asp Tyr Asp Tyr Asp Gly Leu His Asp

785 790 795 800

Thr Glu Asp Lys Ile Lys Gln Tyr Val Glu Gly Ser Ser Ile Pro Val

805 810 815

Pro Thr His Tyr Tyr Ser Ile Ile Thr Ser Cys Leu Asp Phe Thr Gln

820 825 830

Pro Ala Asp Lys Cys Asp Gly Pro Leu Ser Val Ser Ser Phe Ile Leu

835 840 845

Pro His Arg Pro Asp Asn Glu Glu Ser Cys Asn Ser Ser Glu Asp Glu

850 855 860

Ser Lys Trp Val Glu Glu Leu Met Lys MetHi s Thr Ala Arg Val Arg

865 870 875 880

Asp Ile Glu His Leu Thr Ser Leu Asp Phe Phe Arg Lys Thr Ser Arg

885 890 895

Ser Tyr Pro Glu Ile Leu Thr Leu Lys Thr Tyr Leu His Thr Tyr Glu

900 905 910

Ser Glu Ile

915

<210>90

<211>579

<212>PRT

<213>人(Homo sapiens)

<400>90

Met Val Gln Tyr Glu Leu Trp Ala Ala Leu Pro Gly Ala Ser Gly Val

1 5 10 15

Aia Leu Ala Cys Cys Phe Val Ala Ala Ala Val Ala Leu Arg Trp Ser

20 25 30

Gly Arg Arg Thr Ala Arg Gly Ala Val Val Arg Ala Arg Gln Lys Gln

35 40 45

Arg Ala Gly Leu Glu Asn Met Asp Arg Ala Ala Gln Arg Phe Arg Leu

50 55 60

Gln Asn Pro Asp Leu Asp Ser Glu Ala Leu Leu Ala Leu Pro Leu Pro

65 70 75 80

Gln Leu Val Gln Lys Leu His Ser Arg Glu Leu Ala Pro Glu Ala Val

85 90 95

Leu Phe Thr Tyr Val Gly Lys Ala Trp Glu Val Asn Lys Gly Thr Asn

100 105 110

Cys Val Thr Ser Tyr Leu Ala Asp Cys Glu Thr Gln Leu Ser Gln Ala

115 120 125

Pro Arg Gln Gly Leu Leu Tyr Gly Val Pro Val Ser Leu Lys Glu Cys

130 135 140

Phe Thr Tyr Lys Gly Gln Asp Ser Thr Leu Gly Leu Ser Leu Asn Glu

145 150 155 160

Gly Val Pro Ala Glu Cys Asp Ser Val Val Val His Val Leu Lys Leu

165 170 175

Gln Gly Ala Val Pro Phe Val His Thr Asn Val Pro Gln Ser Met Phe

180 185 190

Ser Tyr Asp Cys Ser Asn Pro Leu Phe Gly Gln Thr Val Asn Pro Trp

195 200 205

Lys Ser Ser Lys Ser Pro Gly Gly Ser Ser Gly Gly Glu Gly Ala Leu

210 215 220

Ile Gly Ser Gly Gly Ser Pro Leu Gly Leu Gly Thr Asp Ile Gly Gly

225 230 235 240

Ser Ile Arg Phe Pro Ser Ser Phe Cys Gly Ile Cys Gly Leu Lys Pro

245 250 255

Thr Gly Asn Arg Leu Ser Lys Ser Gly Leu Lys Gly Cys Val Tyr Gly

260 265 270

Gln Glu Ala Val Arg Leu Ser Val Gly Pro Met Ala Arg Asp Val Glu

275 280 285

Ser Leu Ala Leu Cys Leu Arg Ala Leu Leu Cys Glu Asp Met Phe Arg

290 295 300

Leu Asp Pro Thr Val Pro Pro Leu Pro Phe Arg Glu Glu Val Tyr Thr

305 310 315 320

Ser Ser Gln Pro Leu Arg Val Gly Tyr Tyr Glu Thr Asp Asn Tyr Thr

325 330 335

Met Pro Ser Pro Ala Met Arg Arg Ala Val Leu Glu Thr Lys Gln Ser

340 345 350

Leu Glu Ala Ala Gly His Thr Leu Val Pro Phe Leu Pro Ser Asn Ile

355 360 365

Pro His Ala Leu Glu Thr Leu Ser Thr Gly Gly Leu Phe Ser Asp Gly

370 375 380

Gly His Thr Phe Leu Gln Asn Phe Lys Gly Asp Phe Val Asp Pro Cys

385 390 395 400

Leu Gly Asp Leu Val Ser Ile Leu Lys Leu Pro Gln Trp Leu Lys Gly

405 410 415

Leu Leu Ala Phe Leu Val Lys Pro Leu Leu Pro Arg Leu Ser Ala Phe

420 425 430

Leu Ser Asn Met Lys Ser Arg Ser Ala Gly Lys Leu Trp Glu Leu Gln

435 440 445

His Glu Ile Glu Val Tyr Arg Lys Thr Val Ile Ala Gln Trp Arg Ala

450 455 460

Leu Asp Leu Asp Val Val Leu Thr Pro Met Leu Ala Pro Ala Leu Asp

465 470 475 480

Leu Asn Ala Pro Gly Arg Ala Thr Gly Ala Val Ser Tyr Thr Met Leu

485 490 495

Tyr Asn Cys Leu Asp Phe Pro Ala Gly Val Val Pro Val Thr Thr Val

500 505 510

Thr Ala Glu Asp Glu Ala Gln Met Glu His Tyr Arg Gly Tyr Phe Gly

515 520 525

Asp Ile Trp Asp Lys Met Leu Gln Lys Gly Met Lys Lys Ser Val Gly

530 535 540

Leu Pro Val Ala Val Gln Cys Val Ala Leu Pro Trp Gln Glu Glu Leu

545 550 555 560

Cys Leu Arg Phe Met Arg Glu Val Glu Arg Leu Met Thr Pro Glu Lys

565 570 575

Gln Ser Ser

<210>91

<211>236

<212>PRT

<213>人(Homo sapiens)

<400>91

Met Ser Ala Pro Ser Ala Thr Pro Ile Phe Ala Pro Gly Glu Asn Cys

1 5 10 15

Ser Pro Ala Trp Gly Ala Ala Pro Ala Ala Tyr Asp Ala Ala Asp Thr

20 25 30

His Leu Arg Ile Leu Gly Lys Pro Val Met Glu Arg Trp Glu Thr Pro

35 40 45

Tyr Met His Ala Leu Ala Ala Ala Ala Ser Ser Lys Gly Gly Arg Val

50 55 60

Leu Glu Val Gly Phe Gly Met Ala Ile Ala Ala Ser Lys Val Gln Glu

65 70 75 80

Ala Pro Ile Asp Glu His Trp Ile Ile Glu Cys Asn Asp Gly Val Phe

85 90 95

Gln Arg Leu Arg Asp Trp Ala Pro Arg Gln Thr His Lys Val Ile Pro

100 105 110

Leu Lys Gly Leu Trp Glu Asp Val Ala Pro Thr Leu Pro Asp Gly His

115 120 125

Phe Asp Gly Ile Leu Tyr Asp Thr Tyr Pro Leu Ser Glu Glu Thr Trp

130 135 140

His Thr His Gln Phe Asn Phe Ile Lys Asn His Ala Phe Arg Leu Leu

145 150 155 160

Lys Pro Gly Gly Val Leu Thr Tyr Cys Asn Leu Thr Ser Trp Gly Glu

165 170 175

Leu Met Lys Ser Lys Tyr Ser Asp Ile Thr Ile Met Phe Glu Glu Thr

180 185 190

Gln Val Pro Ala Leu Leu Glu Ala Gly Phe Arg Arg Glu Asn Ile Arg

195 200 205

Thr Glu Val Met Ala Leu Val Pro Pro Ala Asp Cys Arg Tyr Tyr Ala

210 215 220

Phe Pro Gln Met Ile Thr Pro Leu Val Thr Lys Gly

225 230 235

<210>92

<211>336

<212>PRT

<213>人(Homo sapiens)

<400>92

Met Ala Ala Ser Leu Arg Leu Leu Gly Ala Ala Ser Gly Leu Arg Tyr

1 5 10 15

Trp Ser Arg Arg Leu Arg Pro Ala Ala Gly Ser Phe Ala Ala Val Cys

20 25 30

Ser Arg Ser Val Ala Ser Lys Thr Pro Val Gly Phe Ile Gly Leu Gly

35 40 45

Asn Met Gly Asn Pro Met Ala Lys Asn Leu Met Lys His Gly Tyr Pro

50 55 60

Leu Ile Ile Tyr Asp Val Phe Pro Asp Ala Cys Lys Glu Phe Gln Asp

65 70 75 80

Ala Gly Glu Gln Val Val Ser Ser Pro Ala Asp Val Ala Glu Lys Ala

85 90 95

Asp Arg Ile Ile Thr Met Leu Pro Thr Ser Ile Asn Ala Ile Glu Ala

100 105 110

Tyr Ser Gly Ala Asn Gly Ile Leu Lys Lys Val Lys Lys Gly Ser Leu

115 120 125

Leu Ile Asp Ser Ser Thr Ile Asp Pro Ala Val Ser Lys Glu Leu Ala

130 135 140

Lys Glu Val Glu Lys Met Gly Ala Val Phe Met Asp Ala Pro Val Ser

145 150 155 160

Gly Gly Val Gly Ala Ala Arg Ser Gly Asn Leu Thr Phe Met Val Gly

165 170 175

Gly Val Glu Asp Glu Phe Ala Ala Ala Gln Glu Leu Leu Gly Cys Met

180 185 190

Gly Ser Asn Val Val Tyr Cys Gly Ala Val Gly Thr Gly Gln Ala Ala

195 200 205

Lys Ile Cys Asn Asn Met Leu Leu Ala Ile Ser Met Ile Gly Thr Ala

210 215 220

Glu Ala Met Asn Leu Gly Ile Arg Leu Gly Leu Asp Pro Lys Leu Leu

225 230 235 240

Ala Lys Ile Leu Asn Met Ser Ser Gly Arg Cys Trp Ser Ser Asp Thr

245 250 255

Tyr Asn Pro Val Pro Gly Val Met Asp Gly Val Pro Ser Ala Asn Asn

260 265 270

Tyr Gln Gly Gly Phe Gly Thr Thr Leu Met Ala Lys Asp Leu Gly Leu

275 280 285

Ala Gln Asp Ser Ala Thr Ser Thr Lys Ser Pro Ile Leu Leu Gly Ser

290 295 300

Leu Ala His Gln Ile Tyr Arg Met Met Cys Ala Lys Gly Tyr Ser Lys

305 310 315 320

Lys Asp Phe Ser Ser Val Phe Gln Phe Leu Arg Glu Glu Glu Thr Phe

325 330 335

<210>93

<211>298

<212>PRT

<213>人(Homo sapiens)

<400>93

Met Glu Glu Lys Gln Ile Leu Cys Val Gly Leu Val Val Leu Asp Val

1 5 10 15

Ile Ser Leu Val Asp Lys Tyr Pro Lys Glu Asp Ser Glu Ile Arg Cys

20 25 30

Leu Ser Gln Arg Trp Gln Arg Gly Gly Asn Ala Ser Asn Ser Cys Thr

35 40 45

Val Leu Ser Leu Leu Gly Ala Pro Cys Ala Phe Met Gly Ser Met Ala

50 55 60

Pro Gly His Val Ala Asp Phe Val Leu Asp Asp Leu Arg Arg Tyr Ser

65 70 75 80

Val Asp Leu Arg Tyr Thr Val Phe Gln Thr Thr Gly Ser Val Pro Ile

85 90 95

Ala Thr Val Ile Ile Asn Glu Ala Ser Gly Ser Arg Thr Ile Leu Tyr

100 105 110

Tyr Asp Arg Ser Leu Pro Asp Val Ser Ala Thr Asp Phe Glu Lys Val

115 120 125

Asp Leu Thr Gln Phe Lys Trp Ile His Ile Glu Gly Arg Asn Ala Ser

130 135 140

Glu Gln Val Lys Met Leu Gln Arg Ile Asp Ala His Asn Thr Arg Gln

145 150 155 160

Pro Pro Glu Gln Lys Ile Arg Val Ser Val Glu Val Glu Lys Pro Arg

165 170 175

Glu Glu Leu Phe Gln Leu Phe Gly Tyr Gly Asp Val Val Phe Val Ser

180 185 190

Lys Asp Val Ala Lys His Leu Gly Phe Gln Ser Ala Glu Glu Ala Leu

195 200 205

Arg Gly Leu Tyr Gly Arg Val Arg Lys Gly Ala Val Leu Val Cys Ala

210 215 220

Trp Ala Glu Glu Gly Ala Asp Ala Leu Gly Pro Asp Gly Lys Leu Leu

225 230 235 240

His Ser Asp Ala Phe Pro Pro Pro Arg Val Val Asp Thr Leu Gly Ala

245 250 255

Gly Asp Thr Phe Asn Ala Ser Val Ile Phe Ser Leu Ser Gln Gly Arg

260 265 270

Ser Val Gln Glu Ala Leu Arg Phe Gly Cys Gln Val Ala Gly Lys Lys

275 280 285

Cys Gly Leu Gln Gly Phe Asp Gly Ile Val

290 295

<210>94

<211>307

<212>PRT

<213>人(Homo sapiens)

<400>94

Met Glu Pro Ser Ser Leu Glu Leu Pro Ala Asp Thr Val Gln Arg Ile

1 5 10 15

Ala Ala Glu Leu Lys Cys His Pro Thr Asp Glu Arg Val Ala Leu His

20 25 30

Leu Asp Glu Glu Asp Lys Leu Arg His Phe Arg Glu Cys Phe Tyr Ile

35 40 45

Pro Lys Ile Gln Asp Leu Pro Pro Val Asp Leu Ser Leu Val Asn Lys

50 55 60

Asp Glu Asn Ala Ile Tyr Phe Leu Gly Asn Ser Leu Gly Leu Gln Pro

65 70 75 80

Lys Met Val Lys Thr Tyr Leu Glu Glu Glu Leu Asp Lys Trp Ala Lys

85 90 95

Ile Ala Ala Tyr Gly His Glu Val Gly Lys Arg Pro Trp Ile Thr Gly

100 105 110

Asp Glu Ser Ile Val Gly Leu Met Lys Asp Ile Val Gly Ala Asn Glu

115 120 125

Lys Glu Ile Ala Leu Met Asn Ala Leu Thr Val Asn Leu His Leu Leu

130 135 140

Met Leu Ser Phe Phe Lys Pro Thr Pro Lys Arg Tyr Lys Ile Leu Leu

145 150 155 160

Glu Ala Lys Ala Phe Pro Ser Asp His Tyr Ala Ile Glu Ser Gln Leu

165 170 175

Gln Leu His Gly Leu Asn Ile Glu Glu Ser Met Arg Met Ile Lys Pro

180 185 190

Arg Glu Gly Glu Glu Thr Leu Arg Ile Glu Asp Ile Leu Glu Val Ile

195 200 205

Glu Lys Glu Gly Asp Ser Ile Ala Val Ile Leu Phe Ser Gly Val His

210 215 220

Phe Tyr Thr Gly Gln His Phe Asn Ile Pro Ala Ile Thr Lys Ala Gly

225 230 235 240

Gln Ala Lys Gly Cys Tyr Val Gly Phe Asp Leu Ala His Ala Val Gly

245 250 255

Asn Val Glu Leu Tyr Leu His Asp Trp Gly Val Asp Phe Ala Cys Trp

260 265 270

Cys Ser Tyr Lys Tyr Leu Asn Ala Gly Ala Gly Gly Ile Ala Gly Ala

275 280 285

Phe Ile His Glu Lys His Ala His Thr Ile Lys Pro Ala Arg Ser Glu

290 295 300

Phe Phe Asn

305

<210>95

<211>1178

<212>PRT

<213>人(Homo sapiens)

<400>95

Met Leu Lys Phe Arg Thr Val His Gly Gly Leu Arg Leu Leu Gly Ile

1 5 10 15

Arg Arg Thr Ser Thr Ala Pro Ala Ala Ser Pro Asn Val Arg Arg Leu

20 25 30

Glu Tyr Lys Pro Ile Lys Lys Val Met Val Ala Asn Arg Gly Glu Ile

35 40 45

Ala Ile Arg Val Phe Arg Ala Cys Thr Glu Leu Gly Ile Arg Thr Val

50 55 60

Ala Ile Tyr Ser Glu Gln Asp Thr Gly Gln Met His Arg Gln Lys Ala

65 70 75 80

Asp Glu Ala Tyr Leu Ile Gly Arg Gly Leu Ala Pro Val Gln Ala Tyr

85 90 95

Leu His Ile Pro Asp Ile Ile Lys Val Ala Lys Glu Asn Asn Val Asp

100 105 110

Ala Val His Pro Gly Tyr Gly Phe Leu Ser Glu Arg Ala Asp Phe Ala

115 120 125

Gln Ala Cys Gln Asp Ala Gly Val Arg Phe Ile Gly Pro Ser Pro Glu

130 135 140

Val Val Arg Lys Met Gly Asp Lys Val Glu Ala Arg Ala Ile Ala Ile

145 150 155 160

Ala Ala Gly Val Pro Val Val Pro Gly Thr Asp Ala Pro Ile Thr Ser

165 170 175

Leu His Glu Ala His Glu Phe Ser Asn Thr Tyr Gly Phe Pro Ile Ile

180 185 190

Phe Lys Ala Ala Tyr Gly Gly Gly Gly Arg Gly Met Arg Val Val His

195 200 205

Ser Tyr Glu Glu Leu Glu Glu Asn Tyr Thr Arg Ala Tyr Ser Glu Ala

210 215 220

Leu Ala Ala Phe Gly Asn Gly Ala Leu Phe Val Glu Lys Phe Ile Glu

225 230 235 240

Lys Pro Arg His Ile Glu Val Gln Ile Leu Gly Asp Gln Tyr Gly Asn

245 250 255

Ile Leu His Leu Tyr Glu Arg Asp Cys Ser Ile Gln Arg Arg His Gln

260 265 270

Lys Val Val Glu Ile Ala Pro Ala Ala His Leu Asp Pro Gln Leu Arg

275 280 285

Thr Arg Leu Thr Ser Asp Ser Val Lys Leu Ala Lys Gln Val Gly Tyr

290 295 300

Glu Asn Ala Gly Thr Val Glu Phe Leu Val Asp Arg His Gly Lys His

305 310 315 320

Tyr Phe Ile Glu Val Asn Ser Arg Leu Gln Val Glu His Thr Val Thr

325 330 335

Glu Glu Ile Thr Asp Val Asp Leu Val His Ala Gln Ile His Val Ser

340 345 350

Glu Gly Arg Ser Leu Pro Asp Leu Gly Leu Arg Gln Glu Asn Ile Arg

355 360 365

Ile Asn Gly Cys Ala Ile Gln Cys Arg Val Thr Thr Glu Asp Pro Ala

370 375 380

Arg Ser Phe Gln Pro Asp Thr Gly Arg Ile Glu Val Phe Arg Ser Gly

385 390 395 400

Glu Gly Met Gly Ile Arg Leu Asp Asn Ala Ser Ala Phe Gln Gly Ala

405 410 415

Val Ile Ser Pro His Tyr Asp Ser Leu Leu Val Lys Val Ile Ala His

420 425 430

Gly Lys Asp His Pro Thr Ala Ala Thr Lys Met Ser Arg Ala Leu Ala

435 440 445

Glu Phe Arg Val Arg Gly Val Lys Thr Asn Ile Ala Phe Leu Gln Asn

450 455 460

Val Leu Asn Asn Gln Gln Phe Leu Ala Gly Thr Val Asp Thr Gln Phe

465 470 475 480

Ile Asp Glu Asn Pro Glu Leu Phe Gln Leu Arg Pro Ala Gln Asn Arg

485 490 495

Ala Gln Lys Leu Leu His Tyr Leu Gly His Val Met Val Asn Gly Pro

500 505 510

Thr Thr Pro Ile Pro Val Lys Ala Ser Pro Ser Pro Thr Asp Pro Val

515 520 525

Val Pro Ala Val Pro Ile Gly Pro Pro Pro Ala Gly Phe Arg Asp Ile

530 535 540

Leu Leu Arg Glu Gly Pro Glu Gly Phe Ala Arg Ala Val Arg Asn His

545 550 555 560

Pro Gly Leu Leu Leu Met Asp Thr Thr Phe Arg Asp Ala His Gln Ser

565 570 575

Leu Leu Ala Thr Arg Val Arg Thr His Asp Leu Lys Lys Ile Ala Pro

580 585 590

Tyr Val Ala His Asn Phe Ser Lys Leu Phe Ser Met Glu Asn Trp Gly

595 600 605

Gly Ala Thr Phe Asp Val Ala Met Arg Phe Leu Tyr Glu Cys Pro Trp

610 615 620

Arg Arg Leu Gln Glu Leu Arg Glu Leu Ile Pro Asn Ile Pro Phe Gln

625 630 635 640

Met Leu Leu Arg Gly Ala Asn Ala Val Gly Tyr Thr Asn Tyr Pro Asp

645 650 655

Asn Val Val Phe Lys Phe Cys Glu Val Ala Lys Glu Asn Gly Met Asp

660 665 670

Val Phe Arg Val Phe Asp Ser Leu Asn Tyr Leu Pro Asn Met Leu Leu

675 680 685

Gly Met Glu Ala Ala Gly Ser Ala Gly Gly Val Val Glu Ala Ala Ile

690 695 700

Ser Tyr Thr Gly Asp Val Ala Asp Pro Ser Arg Thr Lys Tyr Ser Leu

705 710 715 720

Gln Tyr Tyr Met Gly Leu Ala Glu Glu Leu Val Arg Ala Gly Thr His

725 730 735

Ile Leu Cys Ile Lys Asp Met Ala Gly Leu Leu Lys Pro Thr Ala Cys

740 745 750

Thr Met Leu Val Ser Ser Leu Arg Asp Arg Phe Pro Asp Leu Pro Leu

755 760 765

His Ile His Thr His Asp Thr Ser Gly Ala Gly Val Ala Ala Met Leu

770 775 780

Ala Cys Ala Gln Ala Gly Ala Asp Val Val Asp Val Ala Ala Asp Ser

785 790 795 800

Met Ser Gly Met Thr Ser Gln Pro Ser Met Gly Ala Leu Val Ala Cys

805 810 815

Thr Arg Gly Thr Pro Leu Asp Thr Glu Val Pro Met Glu Arg Val Phe

820 825 830

Asp Tyr Ser Glu Tyr Trp Glu Gly Ala Arg Gly Leu Tyr Ala Ala Phe

835 840 845

Asp Cys Thr Ala Thr Met Lys Ser Gly Asn Ser Asp Val Tyr Glu Asn

850 855 860

Glu Ile Pro Gly Gly Gln Tyr Thr Asn Leu His Phe Gln Ala His Ser

865 870 875 880

Met Gly Leu Gly Ser Lys Phe Lys Glu Val Lys Lys Ala Tyr Val Glu

885 890 895

Ala Asn Gln Met Leu Gly Asp Leu Ile Lys Val Thr Pro Ser Ser Lys

900 905 910

Ile Val Gly Asp Leu Ala Gln Phe Met Val Gln Asn Gly Leu Ser Arg

915 920 925

Ala Glu Ala Glu Ala Gln Ala Glu Glu Leu Ser Phe Pro Arg Ser Val

930 935 940

Val Glu Phe Leu Gln Gly Tyr Ile Gly Val Pro His Gly Gly Phe Pro

945 950 955 960

Glu Pro Phe Arg Ser Lys Val Leu Lys Asp Leu Pro Arg Val Glu Gly

965 970 975

Arg Pro Gly Ala Ser Leu Pro Pro Leu Asp Leu Gln Ala Leu Glu Lys

980 985 990

Glu Leu Val Asp Arg His Gly Glu Glu Val Thr Pro Glu Asp Val Leu

995 1000 1005

Ser Ala Ala Met Tyr Pro Asp Val Phe Ala His Phe Lys Asp Phe

1010 1015 1020

Thr Ala Thr Phe Gly Pro Leu Asp Ser Leu Asn Thr Arg Leu Phe

1025 1030 1035

Leu Gln Gly Pro Lys Ile Ala Glu Glu Phe Glu Val Glu Leu Glu

1040 1045 1050

Arg Gly Lys Thr Leu His Ile Lys Ala Leu Ala Val Ser Asp Leu

1055 1060 1065

Asn Arg Ala Gly Gln Arg Gln Val Phe Phe Glu Leu Asn Gly Gln

1070 1075 1080

Leu Arg Ser Ile Leu Val Lys Asp Thr Gln Ala Met Lys Glu Met

1085 1090 1095

His Phe His Pro Lys Ala Leu Lys Asp Val Lys Gly Gln Ile Gly

1100 1105 1110

Ala Pro Met Pro Gly Lys Val Ile Asp Ile Lys Val Val Ala Gly

1115 1120 1125

Ala Lys Val Ala Lys Gly Gln Pro Leu Cys Val Leu Ser Ala Met

1130 1135 1140

Lys Met Glu Thr Val Val Thr Ser Pro Met Glu Gly Thr Val Arg

1145 1150 1155

Lys Val His Val Thr Lys Asp Met Thr Leu Glu Gly Asp Asp Leu

1160 1165 1170

Ile Leu Glu Ile Glu

1175

<210>96

<211>407

<212>PRT

<213>人(Homo sapiens)

<400>96

Met Arg Trp Val Trp Ala Leu Leu Lys Asn Ala Ser Leu Ala Gly Ala

1 5 10 15

Pro Lys Tyr Ile Glu His Phe Ser Lys Phe Ser Pro Ser Pro Leu Ser

20 25 30

Met Lys Gln Phe Leu Asp Phe Gly Ser Ser Asn Ala Cys Glu Lys Thr

35 40 45

Ser Phe Thr Phe Leu Arg Gln Glu Leu Pro Val Arg Leu Ala Asn Ile

50 55 60

Met Lys Glu Ile Asn Leu Leu Pro Asp Arg Val Leu Ser Thr Pro Ser

65 70 75 80

Val Gln Leu Val Gln Ser Trp Tyr Val Gln Ser Leu Leu Asp Ile Met

85 90 95

Glu Phe Leu Asp Lys Asp Pro Glu Asp His Arg Thr Leu Ser Gln Phe

100 105 110

Thr Asp Ala Leu Val Thr Ile Arg Asn Arg His Asn Asp Val Val Pro

115 120 125

Thr Met Ala Gln Gly Val Leu Glu Tyr Lys Asp Thr Tyr Gly Asp Asp

130 135 140

Pro Val Ser Asn Gln Asn Ile Gln Tyr Phe Leu Asp Arg Phe Tyr Leu

145 150 155 160

Ser Arg Ile Ser Ile Arg Met Leu Ile Asn Gln His Thr Leu Ile Phe

165 170 175

Asp Gly Ser Thr Asn Pro Ala His Pro Lys His Ile Gly Ser Ile Asp

180 185 190

Pro Asn Cys Asn Val Ser Glu Val Val Lys Asp Ala Tyr Asp Met Ala

195 200 205

Lys Leu Leu Cys Asp Lys Tyr Tyr Met Ala Ser Pro Asp Leu Glu Ile

210 215 220

Gln Glu Ile Asn Ala Ala Asn Ser Lys Gln Pro Ile His Met Val Tyr

225 230 235 240

Val Pro Ser His Leu Tyr His Met Leu Phe Glu Leu Phe Lys Asn Ala

245 250 255

Met Arg Ala Thr Val Glu Ser His Glu Ser Ser Leu Ile Leu Pro Pro

260 265 270

Ile Lys Val Met Val Ala Leu Gly Glu Glu Asp Leu Ser Ile Lys Met

275 280 285

Ser Asp Arg Gly Gly Gly Val Pro Leu Arg Lys Ile Glu Arg Leu Phe

290 295 300

Ser Tyr Met Tyr Ser Thr Ala Pro Thr Pro Gln Pro Gly Thr Gly Gly

305 310 315 320

Thr Pro Leu Ala Gly Phe Gly Tyr Gly Leu Pro Ile Ser Arg Leu Tyr

325 330 335

Ala Lys Tyr Phe Gln Gly Asp Leu Gln Leu Phe Ser Met Glu Gly Phe

340 345 350

Gly Thr Asp Ala Val Ile Tyr Leu Lys Ala Leu Ser Thr Asp Ser Val

355 360 365

Glu Arg Leu Pro Val Tyr Asn Lys Ser Ala Trp Arg His Tyr Gln Thr

370 375 380

Ile Gln Glu Ala Gly Asp Trp Cys Val Pro Ser Thr Glu Pro Lys Asn

385 390 395 400

Thr Ser Thr Tyr Arg Val Ser

405

<210>97

<211>349

<212>PRT

<213>人(Homo sapiens)

<400>97

Met Glu Ala His Asn Ala Ser Ala Pro Phe Asn Phe Thr Leu Pro Pro

1 5 10 15

Asn Phe Gly Lys Arg Pro Thr Asp Leu Ala Leu Ser Val Ile Leu Val

20 25 30

Phe Met Leu Phe Phe Ile Met Leu Ser Leu Gly Cys Thr Met Glu Phe

35 40 45

Ser Lys Ile Lys Ala His Leu Trp Lys Pro Lys Gly Leu Ala Ile Ala

50 55 60

Leu Val Ala Gln Tyr Gly Ile Met Pro Leu Thr Ala Phe Val Leu Gly

65 70 75 80

Lys Val Phe Arg Leu Lys Asn Ile Glu Ala Leu Ala Ile Leu Val Cys

85 90 95

Gly Cys Ser Pro Gly Gly Asn Leu Ser Asn Val Phe Ser Leu Ala Met

100 105 110

Lys Gly Asp Met Asn Leu Ser Ile Val Met Thr Thr Cys Ser Thr Phe

115 120 125

Cys Ala Leu Gly Met Met Pro Leu Leu Leu Tyr Ile Tyr Ser Arg Gly

130 135 140

Ile Tyr Asp Gly Asp Leu Lys Asp Lys Val Pro Tyr Lys Gly Ile Val

145 150 155 160

Ile Ser Leu Val Leu Val Leu Ile Pro Cys Thr Ile Gly Ile Val Leu

165 170 175

Lys Ser Lys Arg Pro Gln Tyr Met Arg Tyr Val Ile Lys Gly Gly Met

180 185 190

Ile Ile Ile Leu Leu Cys Ser Val Ala Val Thr Val Leu Ser Ala Ile

195 200 205

Asn Val Gly Lys Ser Ile Met Phe Ala Met Thr Pro Leu Leu Ile Ala

210 215 220

Thr Ser Ser Leu Met Pro Phe Ile Gly Phe Leu Leu Gly Tyr Val Leu

225 230 235 240

Ser Ala Leu Phe Cys Leu Asn Gly Arg Cys Arg Arg Thr Val Ser Met

245 250 255

Glu Thr Gly Cys Gln Asn Val Gln Leu Cys Ser Thr Ile Leu Asn Val

260 265 270

Ala Phe Pro Pro Glu Val Ile Gly Pro Leu Phe Phe Phe Pro Leu Leu

275 280 285

Tyr Met Ile Phe Gln Leu Gly Glu Gly Leu Leu Leu Ile Ala Ile Phe

290 295 300

Trp Cys Tyr Glu Lys Phe Lys Thr Pro Lys Asp Lys Thr Lys Met Ile

305 310 315 320

Tyr Thr Ala Ala Thr Thr Glu Glu Thr Ile Pro Gly Ala Leu Gly Asn

325 330 335

Gly Thr Tyr Lys G1y Glu Asp Cys Ser Pro Cys Thr Ala

340 345

<210>98

<211>429

<212>PRT

<213>人(Homo sapiens)

<400>98

Met Ala Ala Gln Gly Tyr Gly Tyr Tyr Arg Thr Val Ile Phe Ser Ala

1 5 10 15

Met Phe Gly Gly Tyr Ser Leu Tyr Tyr Phe Asn Arg Lys Thr Phe Ser

20 25 30

Phe Val Met Pro Ser Leu Val Glu Glu Ile Pro Leu Asp Lys Asp Asp

35 40 45

Leu Gly Phe Ile Thr Ser Ser Gln Ser Ala Ala Tyr Ala Ile Ser Lys

50 55 60

Phe Val Ser Gly Val Leu Ser Asp Gln Met Ser Ala Arg Trp Leu Phe

65 70 75 80

Ser Ser Gly Leu Leu Leu Val Gly Leu Val Asn Ile Phe Phe Ala Trp

85 90 95

Ser Ser Thr Val Pro Val Phe Ala Ala Leu Trp Phe Leu Asn Gly Leu

100 105 110

Ala Gln Gly Leu Gly Trp Pro Pro Cys Gly Lys Val Leu Arg Lys Trp

115 120 125

Phe Glu Pro Ser Gln Phe Gly Thr Trp Trp Ala Ile Leu Ser Thr Ser

130 135 140

Met Asn Leu Ala Gly Gly Leu Gly Pro Ile Leu Ala Thr Ile Leu Ala

145 150 155 160

Gln Ser Tyr Ser Trp Arg Ser Thr Leu Ala Leu Ser Gly Ala Leu Cys

165 170 175

Val Val Val Ser Phe Leu Cys Leu Leu Leu Ile His Asn Glu Pro Ala

180 185 190

Asp Val Gly Leu Arg Asn Leu Asp Pro Met Pro Ser Glu Gly Lys Lys

195 200 205

Gly Ser Leu Lys Glu Glu Ser Thr Leu Gln Glu Leu Leu Leu Ser Pro

210 215 220

Tyr Leu Trp Val Leu Ser Thr Gly Tyr Leu Val Val Phe Gly Val Lys

225 230 235 240

Thr Cys Cys Thr Asp Trp Gly Gln Phe Phe Leu Ile Gln Glu Lys Gly

245 250 255

Gln Ser Ala Leu Val Gly Ser Ser Tyr Met Ser Ala Leu Glu Val Gly

260 265 270

Gly Leu Val Gly Ser Ile Ala Ala Gly Tyr Leu Ser Asp Arg Ala Met

275 280 285

Ala Lys Ala Gly Leu Ser Asn Tyr Gly Asn Pro Arg His Gly Leu Leu

290 295 300

Leu Phe Met Met Ala Gly Met Thr Val Ser Met Tyr Leu Phe Arg Val

305 310 315 320

Thr Val Thr Ser Asp Ser Pro Lys Leu Trp Ile Leu Val Leu Gly Ala

325 330 335

Val Phe Gly Phe Ser Ser Tyr Gly Pro Ile Ala Leu Phe Gly Val Ile

340 345 350

Ala Asn Glu Ser Ala Pro Pro Asn Leu Cys Gly Thr Ser His Ala Ile

355 360 365

Val Gly Leu Met Ala Asn Val Gly Gly Phe Leu Ala Gly Leu Pro Phe

370 375 380

Ser Thr Ile Ala Lys His Tyr Ser Trp Ser Thr Ala Phe Trp Val Ala

385 390 395 400

Glu Val Ile Cys Ala Ala Ser Thr Ala Ala Phe Phe Leu Leu Arg Asn

405 410 415

Ile Arg Thr Lys Met Gly Arg Val Ser Lys Lys Ala Glu

420 425

<210>99

<211>296

<212>PRT

<213>人(Homo sapiens)

<400>99

Met Ala Leu Thr Ser Asp Leu Gly Lys Gln Ile Lys Leu Lys Glu Val

1 5 10 15

Glu Gly Thr Leu Leu Gln Pro Ala Thr Val Asp Asn Trp Ser Gln Ile

20 25 30

Gln Ser Phe Glu Ala Lys Pro Asp Asp Leu Leu Ile Cys Thr Tyr Pro

35 40 45

Lys Ala Gly Thr Thr Trp Ile Gln Glu Ile Val Asp Met Ile Glu Gln

50 55 60

Asn Gly Asp Val Glu Lys Cys Gln Arg Ala Ile Ile Gln His Arg His

65 70 75 80

Pro Phe Ile Glu Trp Ala Arg Pro Pro Gln Pro Ser Gly Val Glu Lys

85 90 95

Ala Lys Ala Met Pro Ser Pro Arg Ile Leu Lys Thr His Leu Ser Thr

100 105 110

Gln Leu Leu Pro Pro Ser Phe Trp Glu Asn Asn Cys Lys Phe Leu Tyr

115 120 125

Val Ala Arg Asn Ala Lys Asp Cys Met Val Ser Tyr Tyr His Phe Gln

130 135 140

Arg Met Asn His Met Leu Pro Asp Pro Gly Thr Trp Glu Glu Tyr Phe

145 150 155 160

Glu Thr Phe Ile Asn Gly Lys Val Val Trp Gly Ser Trp Phe Asp His

165 170 175

Val Lys Gly Trp Trp Glu Met Lys Asp Arg His Gln Ile Leu Phe Leu

180 185 190

Phe Tyr Glu Asp Ile Lys Arg Asp Pro Lys His Glu Ile Arg Lys Val

195 200 205

Met Gln Phe Met Gly Lys Lys Val Asp Glu Thr Val Leu Asp Lys Ile

210 215 220

Val Gln Glu Thr Ser Phe Glu Lys Met Lys Glu Asn Pro Met Thr Asn

225 230 235 240

Arg Ser Thr Val Ser Lys Ser Ile Leu Asp Gln Ser Ile Ser Ser Phe

245 250 255

Met Arg Lys Gly Thr Val Gly Asp Trp Lys Asn His Phe Thr Val Ala

260 265 270

Gln Asn Glu Arg Phe Asp Glu Ile Tyr Arg Arg Lys Met Glu Gly Thr

275 280 285

Ser Ile Asn Phe Cys Met Glu Leu

290 295

<210>100

<211>161

<212>PRT

<213>人(Homo sapiens)

<400>100

Met Asp Gln Glu Thr Val Gly Asn Val Val Leu Leu Ala Ile Val Thr

1 5 10 15

Leu Ile Ser Val Val Gln Asn Gly Phe Phe Ala His Lys Val Glu His

20 25 30

Glu Ser Arg Thr Gln Asn Gly Arg Ser Phe Gln Arg Thr Gly Thr Leu

35 40 45

Ala Phe Glu Arg Val Tyr Thr Ala Asn Gln Asn Cys Val Asp Ala Tyr

50 55 60

Pro Thr Phe Leu Ala Val Leu Trp Ser Ala Gly Leu Leu Cys Ser Gln

65 70 75 80

Val Pro Ala Ala Phe Ala Gly Leu Met Tyr Leu Phe Val Arg Gln Lys

85 90 95

Tyr Phe Val Gly Tyr Leu Gly Glu Arg Thr Gln Ser Thr Pro Gly Tyr

100 105 110

Ile Phe Gly Lys Arg Ile Ile Leu Phe Leu Phe Leu Met Ser Val Ala

115 120 125

Gly Ile Phe Asn Tyr Tyr Leu Ile Phe Phe Phe Gly Ser Asp Phe Glu

130 135 140

Asn Tyr Ile Lys Thr Ile Ser Thr Thr Ile Ser Pro Leu Leu Leu Ile

145 150 155 160

Pro

<210>101

<211>180

<212>PRT

<213>人(Homo sapiens)

<400>101

Met Ala Asp Ser Glu Leu Gln Leu Val Glu Gln Arg Ile Arg Ser Phe

1 5 10 15

Pro Asp Phe Pro Thr Pro Gly Val Val Phe Arg Asp Ile Ser Pro Val

20 25 30

Leu Lys Asp Pro Ala Ser Phe Arg Ala Ala Ile Gly Leu Leu Ala Arg

35 40 45

His Leu Lys Ala Thr His Gly Gly Arg Ile Asp Tyr Ile Ala Gly Leu

50 55 60

Asp Ser Arg Gly Phe Leu Phe Gly Pro Ser Leu Ala Gln Glu Leu Gly

65 70 75 80

Leu Gly Cys Val Leu Ile Arg Lys Arg Gly Lys Leu Pro Gly Pro Thr

85 90 95

Leu Trp Ala Ser Tyr Ser Leu Glu Tyr Gly Lys Ala Glu Leu Glu Ile

100 105 110

Gln Lys Asp Ala Leu Glu Pro Gly Gln Arg Val Val Val Val Asp Asp

115 120 125

Leu Leu Ala Thr Gly Gly Thr Met Asn Ala Ala Cys Glu Leu Leu Gly

130 135 140

Arg Leu Gln Ala Glu Val Leu Glu Cys Val Ser Leu Val Glu Leu Thr

145 150 155 160

Ser Leu Lys Gly Arg Glu Lys Leu Ala Pro Val Pro Phe Phe Ser Leu

165 170 175

Leu Gln Tyr Glu

180

<210>102

<211>227

<212>PRT

<213>人(Homo sapiens)

<400>102

Met Gly Gly Lys Leu Ser Lys Lys Lys Lys Gly Tyr Asn Val Asn Asp

1 5 10 15

Glu Lys Ala Lys Glu Lys Asp Lys Lys Ala Glu Gly Ala Ala Thr Glu

20 25 30

Glu Glu Gly Thr Pro Lys Glu Ser Glu Pro Gln Ala Ala Ala Glu Pro

35 40 45

Ala Glu Ala Lys Glu Gly Lys Glu Lys Pro Asp Gln Asp Ala Glu Gly

50 55 60

Lys Ala Glu Glu Lys Glu Gly Glu Lys Asp Ala Ala Ala Ala Lys Glu

65 70 75 80

Glu Ala Pro Lys Ala Glu Pro Glu Lys Thr Glu Gly Ala Ala Glu Ala

85 90 95

Lys Ala Glu Pro Pro Lys Ala Pro Glu Gln Glu Gln Ala Ala Pro Gly

100 105 110

Pro Ala Ala Gly Gly Glu Ala Pro Lys Ala Ala Glu Ala Ala Ala Ala

115 120 125

Pro Ala Glu Ser Ala Ala Pro Ala Ala Gly Glu Glu Pro Ser Lys Glu

130 135 140

Glu Gly Glu Pro Lys Lys Thr Glu Ala Pro Ala Ala Pro Ala Ala Gln

145 150 155 160

Glu Thr Lys Ser Asp Gly Ala Pro Ala Ser Asp Ser Lys Pro Gly Ser

165 170 175

Ser Glu Ala Ala Pro Ser Ser Lys Glu Thr Pro Ala Ala Thr Glu Ala

180 185 190

Pro Ser Ser Thr Pro Lys Ala Gln Gly Pro Ala Ala Ser Ala Glu Glu

195 200 205

Pro Lys Pro Val Glu Ala Pro Ala Ala Asn Ser Asp Gln Thr Val Thr

210 215 220

Val Lys Glu

225

<210>103

<211>169

<212>PRT

<213>人(Homo sapiens)

<400>103

Met Ala Pro Pro Trp Val Pro Ala Met Gly Phe Thr Leu Ala Pro Ser

1 5 10 15

Leu Gly Cys Phe Val Gly Ser Arg Phe Val His Gly Glu Gly Leu Arg

20 25 30

Trp Tyr Ala Gly Leu Gln Lys Pro Ser Trp His Pro Pro His Trp Val

35 40 45

Leu Gly Pro Val Trp Gly Thr Leu Tyr Ser Ala Met Gly Tyr Gly Ser

50 55 60

Tyr Leu Val Trp Lys Glu Leu Gly Gly Phe Thr Glu Lys Ala Val Val

65 70 75 80

Pro Leu Gly Leu Tyr Thr Gly Gln Leu Ala Leu Asn Trp Ala Trp Pro

85 90 95

Pro Ile Phe Phe Gly Ala Arg Gln Met Gly Trp Ala Leu Val Asp Leu

100 105 110

Leu Leu Val Ser Gly Ala Ala Ala Ala Thr Thr Val Ala Trp Tyr Gln

115 120 125

Val Ser Pro Leu Ala Ala Arg Leu Leu Tyr Pro Tyr Leu Ala Trp Leu

130 135 140

Ala Phe Thr Thr Thr Leu Asn Tyr Cys Val Trp Arg Asp Asn His Gly

145 150 155 160

Trp Arg Gly Gly Arg Arg Leu Pro Glu

165

<210>104

<211>277

<212>PRT

<213>人(Homo sapiens)

<400>104

Met Ser Ser Gly Ile His Val Ala Leu Val Thr Gly Gly Asn Lys Gly

1 5 10 15

Ile Gly Leu Ala Ile Val Arg Asp Leu Cys Arg Leu Phe Ser Gly Asp

20 25 30

Val Val Leu Thr Ala Arg Asp Val Thr Arg Gly Gln Ala Ala Val Gln

35 40 45

Gln Leu Gln Ala Glu Gly Leu Ser Pro Arg Phe His Gln Leu Asp Ile

50 55 60

Asp Asp Leu Gln Ser Ile Arg Ala Leu Arg Asp Phe Leu Arg Lys Glu

65 70 75 80

Tyr Gly Gly Leu Asp Val Leu Val Asn Asn Ala Gly Ile Ala Phe Lys

85 90 95

Val Ala Asp Pro Thr Pro Phe His Ile Gln Ala Glu Val Thr Met Lys

100 105 110

Thr Asn Phe Phe Gly Thr Arg Asp Val Cys Thr Glu Leu Leu Pro Leu

115 120 125

Ile Lys Pro Gln Gly Arg Val Val Asn Val Ser Ser Ile Met Ser Val

130 135 140

Arg Ala Leu Lys Ser Cys Ser Pro Glu Leu Gln Gln Lys Phe Arg Ser

145 150 155 160

Glu Thr Ile Thr Glu Glu Glu Leu Val Gly Leu Met Asn Lys Phe Val

165 170 175

Glu Asp Thr Lys Lys Gly Val His Gln Lys Glu Gly Trp Pro Ser Ser

180 185 190

Ala Tyr Gly Val Thr Lys Ile Gly Val Thr Val Leu Ser Arg Ile His

195 200 205

Ala Arg Lys Leu Ser Glu Gln Arg Lys Gly Asp Lys Ile Leu Leu Asn

210 215 220

Ala Cys Cys Pro Gly Trp Val Arg Thr Asp Met Ala Gly Pro Lys Ala

225 230 235 240

Thr Lys Ser Pro Glu Glu Gly Ala Glu Thr Pro Val Tyr Leu Ala Leu

245 250 255

Leu Pro Pro Asp Ala Glu Gly Pro Hi s Gly Gln Phe Val Ser Glu Lys

260 265 270

Arg Val Glu Gln Trp

275

<210>105

<211>312

<212>PRT

<213>人(Homo sapiens)

<400>105

Met Trp Pro Leu Val Ala Ala Leu Leu Leu Gly Ser Ala Cys Cys Gly

1 5 10 15

Ser Ala Gln Leu Leu Phe Asn Lys Thr Lys Ser Val Glu Phe Thr Phe

20 25 30

Cys Asn Asp Thr Val Val Ile Pro Cys Phe Val Thr Asn Met Glu Ala

35 40 45

Gln Asn Thr Thr Glu Val Tyr Val Lys Trp Lys Phe Lys Gly Arg Asp

50 55 60

Ile Tyr Thr Phe Asp Gly Ala Leu Asn Lys Ser Thr Val Pro Thr Asp

65 70 75 80

Phe Ser Ser Ala Lys Ile Glu Val Ser Gln Leu Leu Lys Gly Asp Ala

85 90 95

Ser Leu Lys Met Asp Lys Ser Asp Ala Val Ser His Thr Gly Asn Tyr

100 105 110

Thr Cys Glu Val Thr Glu Leu Thr Arg Glu Gly Glu Thr Ile Ile Glu

115 120 125

Leu Lys Tyr Arg Val Val Ser Trp Phe Ser Pro Asn Glu Asn Ile Leu

130 135 140

Ile Val Ile Phe Pro Ile Phe Ala Ile Leu Leu Phe Trp Gly Gln Phe

145 150 155 160

Gly Ile Lys Thr Leu Lys Tyr Arg Ser Gly Gly Met Asp Glu Lys Thr

165 170 175

Ile Ala Leu Leu Val Ala Gly Leu Val Ile Thr Val Ile Val Ile Val

180 185 190

Gly Ala Ile Leu Phe Val Pro Gly Glu Tyr Ser Leu Lys Asn Ala Thr

195 200 205

Gly Leu Gly Leu Ile Val Thr Ser Thr Gly Ile Leu Ile Leu Leu His

210 215 220

Tyr Tyr Val Phe Ser Thr Ala Ile Gly Leu Thr Ser Phe Val Ile Ala

225 230 235 240

Ile Leu Val Ile Gln Val Ile Ala Tyr Ile Leu Ala Val Val Gly Leu

245 250 255

Ser Leu Cys Ile Ala Ala Cys Ile Pro Met His Gly Pro Leu Leu Ile

260 265 270

Ser Gly Leu Ser Ile Leu Ala Leu Ala Gln Leu Leu Gly Leu Val Tyr

275 280 285

Met Lys Phe Val Ala Ser Asn Gln Lys Thr Ile Gln Pro Pro Arg Lys

290 295 300

Ala Val Glu Glu Pro Leu Asn Glu

305 310

<210>106

<211>327

<212>PRT

<213>人(Homo sapiens)

<400>106

Met Arg Ala Leu Pro Gly Leu Leu Glu Ala Arg Ala Arg Thr Pro Arg

1 5 10 15

Leu Leu Leu Leu Gln Cys Leu Leu Ala Ala Ala Arg Pro Ser Ser Ala

20 25 30

Asp Gly Ser Ala Pro Asp Ser Pro Phe Thr Ser Pro Pro Leu Arg Glu

35 40 45

Glu Ile Met Ala Asn Asn Phe Ser Leu Glu Ser His Asn Ile Ser Leu

50 55 60

Thr Glu His Ser Ser Met Pro Val Glu Lys Asn Ile Thr Leu Glu Arg

65 70 75 80

Pro Ser Asn Val Asn Leu Thr Cys Gln Phe Thr Thr Ser Gly Asp Leu

85 90 95

Asn Ala Val Asn Val Thr Trp Lys Lys Asp Gly Glu Gln Leu Glu Asn

100 105 110

Asn Tyr Leu Val Ser Ala Thr Gly Ser Thr Leu Tyr Thr Gln Tyr Arg

115 120 125

Phe Thr Ile Ile Asn Ser Lys Gln Met Gly Ser Tyr Ser Cys Phe Phe

130 135 140

Arg Glu Glu Lys Glu Gln Arg Gly Thr Phe Asn Phe Lys Val Pro Glu

145 150 155 160

Leu His Gly Lys Asn Lys Pro Leu Ile Ser Tyr Val Gly Asp Ser Thr

165 170 175

Val Leu Thr Cys Lys Cys Gln Asn Cys Phe Pro Leu Asn Trp Thr Trp

180 185 190

Tyr Ser Ser Asn Gly Ser Val Lys Val Pro Val Gly Val Gln Met Asn

195 200 205

Lys Tyr Val Ile Asn Gly Thr Tyr Ala Asn Glu Thr Lys Leu Lys Ile

210 215 220

Thr Gln Leu Leu Glu Glu Asp Gly Glu Ser Tyr Trp Cys Arg Ala Leu

225 230 235 240

Phe Gln Leu Gly Glu Ser Glu Glu His Ile Glu Leu Val Val Leu Ser

245 250 255

Tyr Leu Val Pro Leu Lys Pro Phe Leu Val Ile Val Ala Glu Val Ile

260 265 270

Leu Leu Val Ala Thr Ile Leu Leu Cys Glu Lys Tyr Thr Gln Lys Lys

275 280 285

Lys Lys His Ser Asp Glu Gly Lys Glu Phe Glu Gln Ile Glu Gln Leu

290 295 300

Lys Ser Asp Asp Ser Asn Gly Ile Glu Asn Asn Val Pro Arg His Arg

305 310 315 320

Lys Asn Glu Ser Leu Gly Gln

325

<210>107

<211>674

<212>PRT

<213>人(Homo sapiens)

<400>107

Met Ala Pro Gly Gln Ala Pro His Gln Ala Thr Pro Trp Arg Asp Ala

1 5 10 15

His Pro Phe Phe Leu Leu Ser Pro Val Met Gly Leu Leu Ser Arg Ala

20 25 30

Trp Ser Arg Leu Arg Gly Leu Gly Pro Leu Glu Pro Trp Leu Val Glu

35 40 45

Ala Val Lys Gly Ala Ala Leu Val Glu Ala Gly Leu Glu Gly Glu Ala

50 55 60

Arg Thr Pro Leu Ala Ile Pro His Thr Pro Trp Gly Arg Arg Pro Gly

65 70 75 80

Glu Glu Ala Glu Asp Ser Gly Gly Pro Gly Glu Asp Arg Glu Thr Leu

85 90 95

Gly Leu Lys Thr Ser Ser Ser Leu Pro Glu Ala Trp Gly Leu Leu Asp

100 105 110

Asp Asp Asp Gly Met Tyr Gly Glu Arg Glu Ala Thr Ser Val Pro Arg

115 120 125

Gly Gln Gly Ser Gln Phe Ala Asp Gly Gln Arg Ala Pro Leu Ser Pro

130 135 140

Ser Leu Leu Ile Arg Thr Leu Gln Gly Ser Asp Lys Asn Pro Gly Glu

145 150 155 160

Glu Lys Ala Glu Glu Glu Gly Val Ala Glu Glu Glu Gly Val Asn Lys

165 170 175

Phe Ser Tyr Pro Pro Ser His Arg Glu Cys Cys Pro Ala Val Glu Glu

180 185 190

Glu Asp Asp Glu Glu Ala Val Lys Lys Glu Ala His Arg Thr Ser Thr

195 200 205

Ser Ala Leu Ser Pro Gly Ser Lys Pro Ser Thr Trp Val Ser Cys Pro

210 215 220

Gly Glu Glu Glu Asn Gln Ala Thr Glu Asp Lys Arg Thr Glu Arg Ser

225 230 235 240

Lys Gly Ala Arg Lys Thr Ser Val Ser Pro Arg Ser Ser Gly Ser Asp

245 250 255

Pro Arg Ser Trp Glu Tyr Arg Ser Gly Glu Ala Ser Glu Glu Lys Glu

260 265 270

Glu Lys Ala His Glu Glu Thr Gly Lys Gly Glu Ala Ala Pro Gly Pro

275 280 285

Gln Ser Ser Ala Pro Ala Gln Arg Pro Gln Leu Lys Ser Trp Trp Cys

290 295 300

Gln Pro Ser Asp Glu Glu Glu Ser Glu Val Lys Pro Leu Gly Ala Ala

305 310 315 320

Glu Lys Asp Gly Glu Ala Glu Cys Pro Pro Cys Ile Pro Pro Pro Ser

325 330 335

Ala Phe Leu Lys Ala Trp Val Tyr Trp Pro Gly Glu Asp Thr Glu Glu

340 345 350

Glu Glu Asp Glu Glu Glu Asp Glu Asp Ser Asp Ser Gly Ser Asp Glu

355 360 365

Glu Glu Gly Glu Ala Glu Ala Ser Ser Ser Thr Pro Ala Thr Gly Val

370 375 380

Phe Leu Lys Ser Trp Val Tyr Gln Pro Gly Glu Asp Thr Glu Glu Glu

385 390 395 400

Glu Asp Glu Asp Ser Asp Thr Gly Ser Ala Glu Asp Glu Arg Glu Ala

405 410 415

Glu Thr Ser Ala Ser Thr Pro Pro Ala Ser Ala Phe Leu Lys Ala Trp

420 425 430

Val Tyr Arg Pro Gly Glu Asp Thr Glu Glu Glu Glu Asp Glu Asp Val

435 440 445

Asp Ser Glu Asp Lys Glu Asp Asp Ser Glu Ala Ala Leu Gly Glu Ala

450 455 460

Glu Ser Asp Pro His Pro Ser His Pro Asp Gln Ser Ala His Phe Arg

465 470 475 480

Gly Trp Gly Tyr Arg Pro Gly Lys Glu Thr Glu Glu Glu Glu Ala Ala

485 490 495

Glu Asp Trp Gly Glu Ala Glu Pro Cys Pro Phe Arg Val Ala Ile Tyr

500 505 510

Val Pro Gly Glu Lys Pro Pro Pro Pro Trp Ala Pro Pro Arg Leu Pro

515 520 525

Leu Arg Leu Gln Arg Arg Leu Lys Arg Pro Glu Thr Pro Thr His Asp

530 535 540

Pro Asp Pro Glu Thr Pro Leu Lys Ala Arg Lys Val Arg Phe Ser Glu

545 550 555 560

Lys Val Thr Val His Phe Leu Ala Val Trp Ala Gly Pro Ala Gln Ala

565 570 575

Ala Arg Gln Gly Pro Trp Glu Gln Leu Ala Arg Asp Arg Ser Arg Phe

580 585 590

Ala Arg Arg Ile Ala Gln Ala Gln Glu Glu Leu Ser Pro Cys Leu Thr

595 600 605

Pro Ala Ala Arg Ala Arg Ala Trp Ala Arg Leu Arg Asn Pro Pro Leu

610 615 620

Ala Pro Ile Pro Ala Leu Thr Gln Thr Leu Pro Ser Ser Ser Val Pro

625 630 635 640

Ser Ser Pro Val Gln Thr Thr Pro Leu Ser Gln Ala Val Ala Thr Pro

645 650 655

Ser Arg Ser Ser Ala Ala Ala Ala Ala Ala Leu Asp Leu Ser Gly Arg

660 665 670

Arg Gly

<210>108

<211>357

<212>PRT

<213>人(Homo sapiens)

<400>108

Met Ala Glu Leu Gln Glu Val Gln Ile Thr Glu Glu Lys Pro Leu Leu

1 5 10 15

Pro Gly Gln Thr Pro Glu Ala Ala Lys Thr His Ser Val Glu Thr Pro

20 25 30

Tyr Gly Ser Val Thr Phe Thr Val Tyr Gly Thr Pro Lys Pro Lys Arg

35 40 45

Pro Ala Ile Leu Thr Tyr His Asp Val Gly Leu Asn Tyr Lys Ser Cys

50 55 60

Phe Gln Pro Leu Phe Gln Phe Glu Asp Met Gln Glu Ile Ile Gln Asn

65 70 75 80

Phe Val Arg Val His Val Asp Ala Pro Gly Met Glu Glu Gly Ala Pro

85 90 95

Val Phe Pro Leu Gly Tyr Gln Tyr Pro Ser Leu Asp Gln Leu Ala Asp

100 105 110

Met Ile Pro Cys Val Leu Gln Tyr Leu Asn Phe Ser Thr Ile Ile Gly

115 120 125

Val Gly Val Gly Ala Gly Ala Tyr Ile Leu Ala Arg Tyr Ala Leu Asn

130 135 140

His Pro Asp Thr Val Glu Gly Leu Val Leu Ile Asn Ile Asp Pro Asn

145 150 155 160

Ala Lys Gly Trp Met Asp Trp Ala Ala His Lys Leu Thr Gly Leu Thr

165 170 175

Ser Ser Ile Pro Glu Met Ile Leu Gly His Leu Phe Ser Gln Glu Glu

180 185 190

Leu Ser Gly Asn Ser Glu Leu Ile Gln Lys Tyr Arg Asn Ile Ile Thr

195 200 205

His Ala Pro Asn Leu Asp Asn Ile Glu Leu Tyr Trp Asn Ser Tyr Asn

210 215 220

Asn Arg Arg Asp Leu Asn Phe Glu Arg Gly Gly Asp Ile Thr Leu Arg

225 230 235 240

Cys Pro Val Met Leu Val Val Gly Asp Gln Ala Pro His Glu Asp Ala

245 250 255

Val Val Glu Cys Asn Ser Lys Leu Asp Pro Thr Gln Thr Ser Phe Leu

260 265 270

Lys Met Ala Asp Ser Gly Gly Gln Pro Gln Leu Thr Gln Pro Gly Lys

275 280 285

Leu Thr Glu Ala Phe Lys Tyr Phe Leu Gln Gly Met Gly Tyr Met Ala

290 295 300

Ser Ser Cys Met Thr Arg Leu Ser Arg Ser Arg Thr Ala Ser Leu Thr

305 310 315 320

Ser Ala Ala Ser Val Asp Gly Asn Arg Ser Arg Ser Arg Thr Leu Ser

325 330 335

Gln Ser Ser Glu Ser Gly Thr Leu Ser Ser Gly Pro Pro Gly His Thr

340 345 350

Met Glu Val Ser Cys

355

<210>109

<211>152

<212>PRT

<213>人(Homo sapiens)

<400>109

Met Ala Asn Cys Glu Arg Thr Phe Ile Ala Ile Lys Pro Asp Gly Val

1 5 10 15

Gln Arg Gly Leu Val Gly Glu Ile Ile Lys Arg Phe Glu Gln Lys Gly

20 25 30

Phe Arg Leu Val Gly Leu Lys Phe Met Gln Ala Ser Glu Asp Leu Leu

35 40 45

Lys Glu His Tyr Val Asp Leu Lys Asp Arg Pro Phe Phe Ala Gly Leu

50 55 60

Val Lys Tyr Met His Ser Gly Pro Val Val Ala Met Val Trp Glu Gly

65 70 75 80

Leu Asn Val Val Lys Thr Gly Arg Val Met Leu Gly Glu Thr Asn Pro

85 90 95

Ala Asp Ser Lys Pro Gly Thr Ile Arg Gly Asp Phe Cys Ile Gln Val

100 105 110

Gly Arg Asn Ile Ile His Gly Ser Asp Ser Val Glu Ser Ala Glu Lys

115 120 125

Glu Ile Gly Leu Trp Phe His Pro Glu Glu Leu Val Asp Tyr Thr Ser

130 135 140

Cys Ala Gln Asn Trp Ile Tyr Glu

145 150

<210>110

<211>211

<212>PRT

<213>人(Homo sapiens)

<400>110

Met Ser Glu Arg Lys Glu Gly Arg Gly Lys Gly Lys Gly Lys Lys Lys

1 5 10 15

Glu Arg Gly Ser Gly Lys Lys Pro Glu Ser Ala Ala Gly Ser Gln Ser

20 25 30

Pro Ala Leu Pro Pro Gln Leu Lys Glu Met Lys Ser Gln Glu Ser Ala

35 40 45

Ala Gly Ser Lys Leu Val Leu Arg Cys Glu Thr Ser Ser Glu Tyr Ser

50 55 60

Ser Leu Arg Phe Lys Trp Phe Lys Asn Gly Asn Glu Leu Asn Arg Lys

65 70 75 80

Asn Lys Pro Gln Asn Ile Lys Ile Gln Lys Lys Pro Gly Lys Ser Glu

85 90 95

Leu Arg Ile Asn Lys Ala Ser Leu Ala Asp Ser Gly Glu Tyr Met Cys

100 105 110

Lys Val Ile Ser Lys Leu Gly Asn Asp Ser Ala Ser Ala Asn Ile Thr

115 120 125

Ile Val Glu Ser Asn Glu Ile Ile Thr Gly Met Pro Ala Ser Thr Glu

130 135 140

Gly Ala Tyr Val Ser Ser Glu Ser Pro Ile Arg Ile Ser Val Ser Thr

145 150 155 160

Glu Gly Ala Asn Thr Ser Ser Ser Thr Ser Thr Ser Thr Thr Gly Thr

165 170 175

Ser His Leu Val Lys Cys Ala Glu Lys Glu Lys Thr Phe Cys Val Asn

180 185 190

Gly Gly Glu Cys Phe Met Val Lys Asp Leu Ser Asn Pro Ser Arg Tyr

195 200 205

Leu Cys Lys

210

<210>111

<211>273

<212>PRT

<213>人(Homo sapiens)

<400>111

Met Thr Phe Asp Asp Leu Lys Ile Gln Thr Val Lys Asp Gln Pro Asp

1 5 10 15

Glu Lys Ser Asn Gly Lys Lys Ala Lys Gly Leu Gln Phe Leu Tyr Ser

20 25 30

Pro Trp Trp Cys Leu Ala Ala Ala Thr Leu Gly Val Leu Cys Leu Gly

35 40 45

Leu Val Val Thr Ile Met Val Leu Gly Met Gln Leu Ser Gln Val Ser

50 55 60

Asp Leu Leu Thr Gln Glu Gln Ala Asn Leu Thr His Gln Lys Lys Lys

65 70 75 80

Leu Glu Gly Gln Ile Ser Ala Arg Gln Gln Ala Glu Glu Ala Ser Gln

85 90 95

Glu Ser Glu Asn Glu Leu Lys Glu Met Ile Glu Thr Leu Ala Arg Lys

100 105 110

Leu Asn Glu Lys Ser Lys Glu Gln Met Glu Leu His His Gln Asn Leu

115 120 125

Asn Leu Gln Glu Thr Leu Lys Arg Val Ala Asn Cys Ser Ala Pro Cys

130 135 140

Pro Gln Asp Trp Ile Trp His Gly Glu Asn Cys Tyr Leu Phe Ser Ser

145 150 155 160

Gly Ser Phe Asn Trp Glu Lys Ser Gln Glu Lys Cys Leu Ser Leu Asp

165 170 175

Ala Lys Leu Leu Lys Ile Asn Ser Thr Ala Asp Leu Asp Phe Ile Gln

180 185 190

Gln Ala Ile Ser Tyr Ser Ser Phe Pro Phe Trp Met Gly Leu Ser Arg

195 200 205

Arg Asn Pro Ser Tyr Pro Trp Leu Trp Glu Asp Gly Ser Pro Leu Met

210 215 220

Pro His Leu Phe Arg Val Arg Gly Ala Val Ser Gln Thr Tyr Pro Ser

225 230 235 240

Gly Thr Cys Ala Tyr Ile Gln Arg Gly Ala Val Tyr Ala Glu Asn Cys

245 250 255

Ile Leu Ala Ala Phe Ser Ile Cys Gln Lys Lys Ala Asn Leu Arg Ala

260 265 270

Gln

<210>112

<211>349

<212>PRT

<213>人(Homo sapiens)

<400>112

Met Ala His Gln Thr Gly Ile His Ala Thr Glu Glu Leu Lys Glu Phe

1 5 10 15

Phe Ala Lys Ala Arg Ala Gly Ser Val Arg Leu Ile Lys Val Val Ile

20 25 30

Glu Asp Glu Gln Leu Val Leu Gly Ala Ser Gln Glu Pro Val Gly Arg

35 40 45

Trp Asp Gln Asp Tyr Asp Arg Ala Val Leu Pro Leu Leu Asp Ala Gln

50 55 60

Gln Pro Cys Tyr Leu Leu Tyr Arg Leu Asp Ser Gln Asn Ala Gln Gly

65 70 75 80

Phe Glu Trp Leu Phe Leu Ala Trp Ser Pro Asp Asn Ser Pro Val Arg

85 90 95

Leu Lys Met Leu Tyr Ala Ala Thr Arg Ala Thr Val Lys Lys Glu Phe

100 105 110

Gly Gly Gly His Ile Lys Asp Glu Leu Phe Gly Thr Val Lys Asp Asp

115 120 125

Leu Ser Phe Ala Gly Tyr Gln Lys His Leu Ser Ser Cys Ala Ala Pro

130 135 140

Ala Pro Leu Thr Ser Ala Glu Arg Glu Leu Gln Gln Ile Arg Ile Asn

145 150 155 160

Glu Val Lys Thr Glu Ile Ser Val Glu Ser Lys His Gln Thr Leu Gln

165 170 175

Gly Leu Ala Phe Pro Leu Gln Pro Glu Ala Gln Arg Ala Leu Gln Gln

180 185 190

Leu Lys Gln Lys Met Val Asn Tyr Ile Gln Met Lys Leu Asp Leu Glu

195 200 205

Arg Glu Thr Ile Glu Leu Val His Thr Glu Pro Thr Asp Val Ala Gln

210 215 220

Leu Pro Ser Arg Val Pro Arg Asp Ala Ala Arg Tyr His Phe Phe Leu

225 230 235 240

Tyr Lys His Thr His Glu Gly Asp Pro Leu Glu Ser Val Val Phe Ile

245 250 255

Tyr Ser Met Pro Gly Tyr Lys Cys Ser Ile Lys Glu Arg Met Leu Tyr

260 265 270

Ser Ser Cys Lys Ser Arg Leu Leu Asp Ser Val Glu Gln Asp Phe His

275 280 285

Leu Glu Ile Ala Lys Lys Ile Glu Ile Gly Asp Gly Ala Glu Leu Thr

290 295 300

Ala Glu Phe Leu Tyr Asp Glu Val His Pro Lys Gln His Ala Phe Lys

305 310 315 320

Gln Ala Phe Ala Lys Pro Lys Gly Pro Gly Gly Lys Arg Gly His Lys

325 330 335

Arg Leu Ile Arg Gly Pro Gly Glu Asn Gly Asp Asp Ser

340 345

<210>113

<211>298

<212>PRT

<213>人(Homo sapiens)

<400>113

Met Ser Leu Tyr Pro Ser Leu Glu Asp Leu Lys Val Asp Lys Val Ile

1 5 10 15

Gln Ala Gln Thr Ala Phe Ser Ala Asn Pro Ala Asn Pro Ala Ile Leu

20 25 30

Ser Glu Ala Ser Ala Pro Ile Pro His Asp Gly Asn Leu Tyr Pro Arg

35 40 45

Leu Tyr Pro Glu Leu Ser Gln Tyr Met Gly Leu Ser Leu Asn Glu Glu

50 55 60

Glu Ile Arg Ala Asn Val Ala Val Val Ser Gly Ala Pro Leu Gln Gly

65 70 75 80

Gln Leu Val Ala Arg Pro Ser Ser Ile Asn Tyr Met Val Ala Pro Val

85 90 95

Thr Gly Asn Asp Val Gly Ile Arg Arg Ala Glu Ile Lys Gln Gly Ile

100 105 110

Arg Glu Val Ile Leu Cys Lys Asp Gln Asp Gly Lys Ile Gly Leu Arg

115 120 125

Leu Lys Ser Ile Asp Asn Gly Ile Phe Val Gln Leu Val Gln Ala Asn

130 135 140

Ser Pro Ala Ser Leu Val Gly Leu Arg Phe Gly Asp Gln Val Leu Gln

145 150 155 160

Ile Asn Gly Glu Asn Cys Ala Gly Trp Ser Ser Asp Lys Ala His Lys

165 170 175

Val Leu Lys Gln Ala Phe Gly Glu Lys Ile Thr Met Thr Ile Arg Asp

180 185 190

Arg Pro Phe Glu Arg Thr Ile Thr Met His Lys Asp Ser Thr Gly His

195 200 205

Val Gly Phe Ile Phe Lys Asn Gly Lys Ile Thr Ser Ile Val Lys Asp

210 215 220

Ser Ser Ala Ala Arg Asn Gly Leu Leu Thr Glu His Asn Ile Cys Glu

225 230 235 240

Ile Asn Gly Gln Asn Val Ile Gly Leu Lys Asp Ser Gln Ile Ala Asp

245 250 255

Ile Leu Ser Thr Ser Gly Thr Val Val Thr Ile Thr Ile Met Pro Ala

260 265 270

Phe Ile Phe Glu His Ile Ile Lys Arg Met Ala Pro Ser Ile Met Lys

275 280 285

Ser Leu Met Asp His Thr Ile Pro Glu Val

290 295

<210>114

<211>79

<212>PRT

<213>人(Homo sapiens)

<400>114

Met Lys Val Thr Gly Ile Phe Leu Leu Ser Ala Leu Ala Leu Leu Ser

1 5 10 15

Leu Ser Gly Asn Thr Gly Ala Asp Ser Leu Gly Arg Glu Ala Lys Cys

20 25 30

Tyr Asn Glu Leu Asn Gly Cys Thr Lys Ile Tyr Asp Pro Val Cys Gly

35 40 45

Thr Asp Gly Asn Thr Tyr Pro Asn Glu Cys Val Leu Cys Phe Glu Asn

50 55 60

Arg Lys Arg Gln Thr Ser Ile Leu Ile Gln Lys Ser Gly Pro Cys

65 70 75

<210>115

<211>246

<212>PRT

<213>人(Homo sapiens)

<400>115

Met Gly Asp Arg Glu Gln Leu Leu Gln Arg Ala Arg Leu Ala Glu Gln

1 5 10 15

Ala Glu Arg Tyr Asp Asp Met Ala Ser Ala Met Lys Ala Val Thr Glu

20 25 30

Leu Asn Glu Pro Leu Ser Asn Glu Asp Arg Asn Leu Leu Ser Val Ala

35 40 45

Tyr Lys Asn Val Val Gly Ala Arg Arg Ser Ser Trp Arg Val Ile Ser

50 55 60

Ser Ile Glu Gln Lys Thr Met Ala Asp Gly Asn Glu Lys Lys Leu Glu

65 70 75 80

Lys Val Lys Ala Tyr Arg Glu Lys Ile Glu Lys Glu Leu Glu Thr Val

85 90 95

Cys Asn Asp Val Leu Ser Leu Leu Asp Lys Phe Leu Ile Lys Asn Cys

100 105 110

Asn Asp Phe Gln Tyr Glu Ser Lys Val Phe Tyr Leu Lys Met Lys Gly

115 120 125

Asp Tyr Tyr Arg Tyr Leu Ala Glu Val Ala Ser Gly Glu Lys Lys Asn

130 135 140

Ser Val Val Glu Ala Ser Glu Ala Ala Tyr Lys Glu Ala Phe Glu Ile

145 150 155 160

Ser Lys Glu Gln Met Gln Pro Thr His Pro Ile Arg Leu Gly Leu Ala

165 170 175

Leu Asn Phe Ser Val Phe Tyr Tyr Glu Ile Gln Asn Ala Pro Glu Gln

180 185 190

Ala Cys Leu Leu Ala Lys Gln Ala Phe Asp Asp Ala Ile Ala Glu Leu

195 200 205

Asp Thr Leu Asn Glu Asp Ser Tyr Lys Asp Ser Thr Leu Ile Met Gln

210 215 220

Leu Leu Arg Asp Asn Leu Thr Leu Trp Thr Ser Asp Gln Gln Asp Glu

225 230 235 240

Glu Ala Gly Glu Gly Asn

245

<210>116

<211>97

<212>PRT

<213>人(Homo sapiens)

<400>116

Met Pro Ser Gln Met Glu His Ala Met Glu Thr Met Met Phe Thr Phe

1 5 10 15

His Lys Phe Ala Gly Asp Lys Gly Tyr Leu Thr Lys Glu Asp Leu Arg

20 25 30

Val Leu Met Glu Lys Glu Phe Pro Gly Phe Leu Glu Asn Gln Lys Asp

35 40 45

Pro Leu Ala Val Asp Lys Ile Met Lys Asp Leu Asp Gln Cys Arg Asp

50 55 60

Gly Lys Val Gly Phe Gln Ser Phe Phe Ser Leu Ile Ala Gly Leu Thr

65 70 75 80

Ile Ala Cys Asn Asp Tyr Phe Val Val His Met Lys Gln Lys Gly Lys

85 90 95

Lys

<210>117

<211>158

<212>PRT

<213>人(Homo sapiens)

<400>117

Met Ser His Gly Lys Gly Thr Asp Met Leu Pro Glu Ile Ala Ala Ala

1 5 10 15

Val Gly Phe Leu Ser Ser Leu Leu Arg Thr Arg Gly Cys Val Ser Glu

20 25 30

Gln Arg Leu Lys Val Phe Ser Gly Ala Leu Gln Glu Ala Leu Thr Glu

35 40 45

His Tyr Lys His His Trp Phe Pro Glu Lys Pro Ser Lys Gly Ser Gly

50 55 60

Tyr Arg Cys Ile Arg Ile Asn His Lys Met Asp Pro Ile Ile Ser Arg

65 70 75 80

Val Ala Ser Gln Ile Gly Leu Ser Gln Pro Gln Leu His Gln Leu Leu

85 90 95

Pro Ser Glu Leu Thr Leu Trp Val Asp Pro Tyr Glu Val Ser Tyr Arg

100 105 110

Ile Gly Glu Asp Gly Ser Ile Cys Val Leu Tyr Glu Glu Ala Pro Leu

115 120 125

Ala Ala Ser Cys Gly Leu Leu Thr Cys Lys Asn Gln Val Leu Leu Gly

130 135 140

Arg Ser Ser Pro Ser Lys Asn Tyr Val Met Ala Val Ser Ser

145 150 155

<210>118

<211>624

<212>PRT

<213>人(Homo sapiens)

<400>118

Met Glu Ile Pro Gly Ser Leu Cys Lys Lys Val Lys Leu Ser Asn Asn

1 5 10 15

Ala Gln Asn Trp Gly Met Gln Arg Ala Thr Asn Val Thr Tyr Gln Ala

20 25 30

His His Val Ser Arg Asn Lys Arg Gly Gln Val Val Gly Thr Arg Gly

35 40 45

Gly Phe Arg Gly Cys Thr Val Trp Leu Thr Gly Leu Ser Gly Ala Gly

50 55 60

Lys Thr Thr Val Ser Met Ala Leu Glu Glu Tyr Leu Val Cys His Gly

65 70 75 80

Ile Pro Cys Tyr Thr Leu Asp Gly Asp Asn Ile Arg Gln Gly Leu Asn

85 90 95

Lys Asn Leu Gly Phe Ser Pro Glu Asp Arg Glu Glu Asn Val Arg Arg

100 105 110

Ile Ala Glu Val Ala Lys Leu Phe Ala Asp Ala Gly Leu Val Cys Ile

115 120 125

Thr Ser Phe Ile Ser Pro Tyr Thr Gln Asp Arg Asn Asn Ala Arg Gln

130 135 140

Ile His Glu Gly Ala Ser Leu Pro Phe Phe Glu Val Phe Val Asp Ala

145 150 155 160

Pro Leu His Val Cys Glu Gln Arg Asp Val Lys Gly Leu Tyr Lys Lys

165 170 175

Ala Arg Ala Gly Glu Ile Lys Gly Phe Thr Gly Ile Asp Ser Glu Tyr

180 185 190

Glu Lys Pro Glu Ala Pro Glu Leu Val Leu Lys Thr Asp Ser Cys Asp

195 200 205

Val Asn Asp Cys Val Gln Gln Val Val Glu Leu Leu Gln Glu Arg Asp

210 215 220

Ile Val Pro Val Asp Ala Ser Tyr Glu Val Lys Glu Leu Tyr Val Pro

225 230 235 240

Glu Asn Lys Leu His Leu Ala Lys Thr Asp Ala Glu Thr Leu Pro Ala

245 250 255

Leu Lys Ile Asn Lys Val Asp Met Gln Trp Val Gln Val Leu Ala Glu

260 265 270

Gly Trp Ala Thr Pro Leu Asn Gly Phe Met Arg Glu Arg Glu Tyr Leu

275 280 285

Gln Cys Leu His Phe Asp Cys Leu Leu Asp Gly Gly Val Ile Asn Leu

290 295 300

Ser Val Pro Ile Val Leu Thr Ala Thr His Glu Asp Lys Glu Arg Leu

305 310 315 320

Asp Gly Cys Thr Ala Phe Ala Leu Met Tyr Glu Gly Arg Arg Val Ala

325 330 335

Ile Leu Arg Asn Pro Glu Phe Phe Glu His Arg Lys Glu Glu Arg Cys

340 345 350

Ala Arg Gln Trp Gly Thr Thr Cys Lys Asn His Pro Tyr Ile Lys Met

355 360 365

Val Met Glu Gln Gly Asp Trp Leu Ile Gly Gly Asp Leu Gln Val Leu

370 375 380

Asp Arg Val Tyr Trp Asn Asp Gly Leu Asp Gln Tyr Arg Leu Thr Pro

385 390 395 400

Thr Glu Leu Lys Gln Lys Phe Lys Asp Met Asn Ala Asp Ala Val Phe

405 410 415

Ala Phe Gln Leu Arg Asn Pro Val His Asn Gly His Ala Leu Leu Met

420 425 430

Gln Asp Thr His Lys Gln Leu Leu Glu Arg Gly Tyr Arg Arg Pro Val

435 440 445

Leu Leu Leu His Pro Leu Gly Gly Trp Thr Lys Asp Asp Asp Val Pro

450 455 460

Leu Met Trp Arg Met Lys Gln His Ala Ala Val Leu Glu Glu Gly Val

465 470 475 480

Leu Asn Pro Glu Thr Thr Val Val Ala Ile Phe Pro Ser Pro Met Met

485 490 495

Tyr Ala Gly Pro Thr Glu Val Gln Trp His Cys Arg Ala Arg Met Val

500 505 510

Ala Gly Ala Asn Phe Tyr Ile Val Gly Arg Asp Pro Ala Gly Met Pro

515 520 525

His Pro Glu Thr Gly Lys Asp Leu Tyr Glu Pro Ser His Gly Ala Lys

530 535 540

Val Leu Thr Met Ala Pro Gly Leu Ile Thr Leu Glu Ile Val Pro Phe

545 550 555 560

Arg Val Ala Ala Tyr Asn Lys Lys Lys Lys Arg Met Asp Tyr Tyr Asp

565 570 575

Ser Glu His His Glu Asp Phe Glu Phe Ile Ser Gly Thr Arg Met Arg

580 585 590

Lys Leu Ala Arg Glu Gly Gln Lys Pro Pro Glu Gly Phe Met Ala Pro

595 600 605

Lys Ala Trp Thr Val Leu Thr Glu Tyr Tyr Lys Ser Leu Glu Lys Ala

610 615 620

<210>119

<211>99

<212>PRT

<213>人(Homo sapiens)

<400>119

Met Phe Ser Lys Met Ala Thr Tyr Leu Thr Gly Glu Leu Thr Ala Thr

1 5 10 15

Ser Glu Asp Tyr Lys Leu Leu Glu Asn Met Asn Lys Leu Thr Ser Leu

20 25 30

Lys Tyr Leu Glu Met Lys Asp Ile Ala Ile Asn Ile Ser Arg Asn Leu

35 40 45

Lys Asp Leu Asn Gln Lys Tyr Ala Gly Leu Gln Pro Tyr Leu Asp Gln

50 55 60

Ile Asn Val Ile Glu Glu Gln Val Ala Ala Leu Glu Gln Ala Ala Tyr

65 70 75 80

Lys Leu Asp Ala Tyr Ser Lys Lys Leu Glu Ala Lys Tyr Lys Lys Leu

85 90 95

Glu Lys Arg

<210>120

<211>491

<212>PRT

<213>人(Homo sapiens)

<400>120

Met Cys Asn Thr Asn Met Ser Val Pro Thr Asp Gly Ala Val Thr Thr

1 5 10 15

Ser Gln Ile Pro Ala Ser Glu Gln Glu Thr Leu Val Arg Pro Lys Pro

20 25 30

Leu Leu Leu Lys Leu Leu Lys Ser Val Gly Ala Gln Lys Asp Thr Tyr

35 40 45

Thr Met Lys Glu Val Leu Phe Tyr Leu Gly Gln Tyr Ile Met Thr Lys

50 55 60

Arg Leu Tyr Asp Glu Lys Gln Gln His Ile Val Tyr Cys Ser Asn Asp

65 70 75 80

Leu Leu Gly Asp Leu Phe Gly Val Pro Ser Phe Ser Val Lys Glu His

85 90 95

Arg Lys Ile Tyr Thr Met Ile Tyr Arg Asn Leu Val Val Val Asn Gln

100 105 110

Gln Glu Ser Ser Asp Ser Gly Thr Ser Val Ser Glu Asn Arg Cys His

115 120 125

Leu Glu Gly Gly Ser Asp Gln Lys Asp Leu Val Gln Glu Leu Gln Glu

130 135 140

Glu Lys Pro Ser Ser Ser His Leu Val Ser Arg Pro Ser Thr Ser Ser

145 150 155 160

Arg Arg Arg Ala Ile Ser Glu Thr Glu Glu Asn Ser Asp Glu Leu Ser

165 170 175

Gly Glu Arg Gln Arg Lys Arg His Lys Ser Asp Ser Ile Ser Leu Ser

180 185 190

Phe Asp Glu Ser Leu Ala Leu Cys Val Ile Arg Glu Ile Cys Cys Glu

195 200 205

Arg Ser Ser Ser Ser Glu Ser Thr Gly Thr Pro Ser Asn Pro Asp Leu

210 215 220

Asp Ala Gly Val Ser Glu His Ser Gly Asp Trp Leu Asp Gln Asp Ser

225 230 235 240

Val Ser Asp Gln Phe Ser Val Glu Phe Glu Val Glu Ser Leu Asp Ser

245 250 255

Glu Asp Tyr Ser Leu Ser Glu Glu Gly Gln Glu Leu Ser Asp Glu Asp

260 265 270

Asp Glu Val Tyr Gln Val Thr Val Tyr Gln Ala Gly Glu Ser Asp Thr

275 280 285

Asp Ser Phe Glu Glu Asp Pro Glu Ile Ser Leu Ala Asp Tyr Trp Lys

290 295 300

Cys Thr Ser Cys Asn Glu Met Asn Pro Pro Leu Pro Ser His Cys Asn

305 310 315 320

Arg Cys Trp Ala Leu Arg Glu Asn Trp Leu Pro Glu Asp Lys Gly Lys

325 330 335

Asp Lys Gly Glu Ile Ser Glu Lys Ala Lys Leu Glu Asn Ser Thr Gln

340 345 350

Ala Glu Glu Gly Phe Asp Val Pro Asp Cys Lys Lys Thr Ile Val Asn

355 360 365

Asp Ser Arg Glu Ser Cys Val Glu Glu Asn Asp Asp Lys Ile Thr Gln

370 375 380

Ala Ser Gln Ser Gln Glu Ser Glu Asp Tyr Ser Gln Pro Ser Thr Ser

385 390 395 400

Ser Ser Ile Ile Tyr Ser Ser Gln Glu Asp Val Lys Glu Phe Glu Arg

405 410 415

Glu Glu Thr Gln Asp Lys Glu Glu Ser Val Glu Ser Ser Leu Pro Leu

420 425 430

Asn Ala Ile Glu Pro Cys Val Ile Cys Gln Gly Arg Pro Lys Asn Gly

435 440 445

Cys Ile Val His Gly Lys Thr Gly His Leu Met Ala Cys Phe Thr Cys

450 455 460

Ala Lys Lys Leu Lys Lys Arg Asn Lys Pro Cys Pro Val Cys Arg Gln

465 470 475 480

Pro Ile Gln Met Ile Val Leu Thr Tyr Phe Pro

485 490

Claims

1.一种检测肝纤维化和/或肝硬化生物标志的方法，包括

从患者中获得生物样本，以及

分析该样本中至少一基因的异常表达，该基因编码蛋白质，其选自序列号：1至63及其人类直向同源物(orthologs)，其中该基因的异常表达表示有肝纤维化和/或肝硬化。

2.权利要求1所述的检测肝纤维化和/或肝硬化生物标志的方法，其中该人类直向同源基因编码蛋白质，其包括序列号：64至120。

3.权利要求1所述的检测肝纤维化和/或肝硬化生物标志的方法，其中该至少一基因的表达增加表示有肝纤维化和/或肝硬化，该基因编码蛋白质，且其选自序列号：7至23、42至63及其人类直向同源基因(orthologs)。

4.权利要求2所述的检测肝纤维化和/或肝硬化生物标志的方法，其中该至少一基因的表达增加表示有肝纤维化和/或肝硬化，该基因编码蛋白质，其选自序列号：68至82及序列号100至120。

5.权利要求1所述的检测肝纤维化和/或肝硬化生物标志的方法，其中该至少一基因的表达下降表示有肝纤维化和/或肝硬化，该基因编码蛋白质，且其选自序列号：1至6、24至41及其人类直向同源基因(orthologs)。

6.权利要求2所述的检测肝纤维化和/或肝硬化生物标志的方法，其中至少一基因的表达下降表示有肝纤维化和/或肝硬化，该基因编码蛋白质，且其选自序列号：64至67及83至99。

7.一种检测肝纤维化和/或肝硬化生物标志的方法，包括

从患者中获得生物样本，以及

分析该样本中至少一基因的异常表达，该基因编码蛋白质，且其选自序列号：1至120，其中该基因的异常表达表示有肝纤维化和/或肝硬化。

8.权利要求7所述的检测肝纤维化和/或肝硬化生物标志的方法，其中该异常表达的基因编码蛋白质，该基因的功能与癌症、细胞周期及细胞形态有关，且其选自序列号：9、69、12、72、4、65、17、76、7、68、19、78、5、66、20、79、22、81、21及80。

9.权利要求7所述的检测肝纤维化和/或肝硬化生物标志的方法，其中该异常表达的基因编码蛋白质，该基因功能与脂质代谢、小分子生化及组织损伤与异常有关，其选自序列号：10、70、3、64、14、73、15及74。

10.权利要求7所述的检测肝纤维化和/或肝硬化生物标志的方法，其中该异常表达的基因编码一蛋白质，该蛋白质的功能与血液疾病、内分液系统的发育、功能及神经系统的发育与功能有关，其包括序列号：13。

11.权利要求7所述的检测肝纤维化和/或肝硬化生物标志的方法，其中该异常表达的基因编码蛋白质，该基因的功能与癌症、细胞形态及皮肤疾病与症状有关，其选自序列号：8、44、102、45、103、48、106、31、90、35、93、50、108、51、109、40及98。

12.权利要求7所述的检测肝纤维化和/或肝硬化生物标志的方法，其中该异常表达的基因编码蛋白质，该基因的功能与脂质代谢、小分子生化及分子传输有关，其选自序列号：25、84、42、100、27、86、47、105、36、94、53、111、37、95、38、96及107。

13.权利要求7所述的检测肝纤维化和/或肝硬化生物标志的方法，其中该异常表达的基因编码蛋白质，该基因的功能与癌症、细胞移动、细胞生长及分化有关，其选自序列号：59、117、46、104、30、89、52、110、58、116、55、113、39、97、56、114、57及115。

14.一种鉴定化合物的方法，该化合物降低至少一基因的异常表达，该基因编码蛋白质，其选自序列号：7至23、42至63及其人类直向同源基因(orthologs)，包括

利用表达至少一基因的细胞，该基因编码蛋白质，且其选自序列号：7至23、42至63及其人类直向同源基因；

使该细胞与试验化合物接触，以及

在该试验化合物的存在下，检测至少一基因的表达的降低，其中该表达的降低表示抑制或治疗肝纤维化和/或肝硬化的征状。

15.一种鉴定化合物的方法，该化合物系增加至少一基因的表达，该基因编码蛋白质，其选自序列号：1至6、24至41及其人类直向同源基因，包括

利用细胞，其表达至少一基因，该基因编码蛋白质，且其选自序列号：1至6及24至41及其人类直向同源基因；

使该细胞与试验化合物接触，以及

在该试验化合物的存在下，检测至少一基因的表达的增加，其中该表达的增加表示抑制或治疗肝纤维化和/或肝硬化的征状。

16.一种检测肝纤维化和/或肝硬化的生物标志的方法，包括

从无肝纤维化和/或肝硬化的个体获得第一生物样本；

从有肝纤维化和/或肝硬化的个体获得第二生物样本；

测定该第一及第二生物样本中的至少一蛋白质的量，其选自序列号：1至120，以及

其中该第一生物样本与该第二生物样本中该蛋白质含量的具有差异，则显示该第二个体具有肝纤维化和/或肝硬化。

17.权利要求16所述的检测肝纤维化和/或肝硬化的生物标志的方法，以Western Blotting或酶联结合免疫吸附法(ELISA)测定其中至少一蛋白质的含量。

18.权利要求17所述的检测肝纤维化和/或肝硬化的生物标志的方法，其中至少一蛋白质选自序列号：1至63。

19.权利要求17所述的检测肝纤维化和/或肝硬化的生物标志的方法，其中至少一蛋白质选自序列编识号：64至120。