细胞周期关卡与pik相关的激酶材料和方法

专利名称：细胞周期关卡与pik相关的激酶材料和方法
技术领域：
本发明广泛涉及编码细胞周期关卡有关磷脂酰肌醇激酶(PIK)的基因以及细胞中对DNA损伤反应必需的蛋白。关卡激酶在监督由于复制错误、DNA错配、辐射处理或化疗药物而发生的DNA损伤中起作用。这些激酶在DNA损伤后导致细胞周期停滞的调节通路中，在DNA复制开始前给细胞通知和时间以修复损伤方面是必需的。更特别地，本发明涉及一种新的人与PIK相关的激酶，哺乳动物细胞周期监督1(MCCS1)，编码PIK相关激酶的多核苷酸以及测定和调节该激酶和相关激酶酶活的方法。
背景真核细胞生长和分裂的过程是由G1期、S期、G2期和M期四个时相组成的体细胞或有丝分裂细胞周期。G1，S，和G2期统称为细胞周期和分裂间期。在所有真核细胞种类中，细胞周期在其基本过程和调节方式上是结构和功能保守的。在G1(间)期，细胞的生物合成活性高速进展。当DNA合成开始时S(合成)期开始，在细胞核的DNA含量得到复制并形成相同的两套染色体时S期结束。细胞然后进入G2(间)期直至有丝分裂开始。在有丝分裂中，染色体配对、分离并形成两个新核，在胞质分裂时细胞本身分成两个子细胞，每个子细胞得到含有两套染色体中之一的一个核。有丝分裂和胞质分裂共同形成细胞周期的M(有丝分裂)期。胞质分裂结束M期并标志下一个细胞周期分裂间期的开始。细胞周期中事件进行的程序是严密调控的，一个细胞周期事件的开始依赖于前一个细胞周期事件的完成。这使细胞从一代到下一代遗传物质的复制和分离保持忠实性。
术语“细胞周期关卡”指细胞复制过程中使不连续事件结合起来的蛋白、信号、步骤和反馈控制，使得在细胞周期中保持基本的依赖性。本发明特别涉及确保有丝分裂延迟直至DNA合成完成和/或DNA损伤的准确修复出现的细胞周期关卡。
细胞周期关卡的失效使个体倾向于或直接导致许多疾病状态如癌症，运动失调性毛细血管扩张症，胚胎畸形以及多种与异常B和T细胞生成相关的免疫缺陷。后者与病理状态如狼疮，关节炎和自身免疫疾病有关。因此深入的研究着力集中在识别细胞周期关卡和关卡功能所必需的蛋白。
对酵母菌pombe裂殖酵母和酿酒酵母的基因分析已鉴定了几种响应离子化辐射(IR)的细胞周期停滞和DNA修复重要的基因。综述见Carr和Hoekstra，Trends in Cell Biology.532-40(1995)。在两种酵母中均鉴定的一种这类基因是细胞周期停滞在G2期的DNA损伤关卡和监控DNA合成的完成并将细胞周期停滞在S期的相关关卡。该基因在pombe裂殖酵母[Seaton et al.，Gene，11983-89(1992)]中命名为rad3+，在啤酒酵母中命名为MECI/ESR1[Kato et al.，Nuc.Acids.Res.，22(15)3104-3112(1994)]，此后称做rad3+。具有rak3+突变的细胞不能觉察或对DNA损伤有适当的反应，因而暴露于断裂剂或事件(如IR，DNA损伤剂和影响染色体完整的突变)后比野生型细胞更快地丧失生存能力。见Weinert等，GENES & DEVELOPMENT，8652-665(1994)和Al-Khodairy等，EMBO J.，11(4)1343-1350(1992)。对IR的敏感性(放射敏感性)可通过关卡反应或直接DNA修复反应的缺陷而引起。
rad3+基因的产物是一个约270KD的蛋白，归于一个正在壮大的高分子量PIK相关激酶的家族。见Hunter，Cell，831-4(1995)讨论了该激酶家族。此基因家族成员中发现的催化区域一级结构与已详细表征的磷脂酰肌醇激酶紧密相关。此结构关系最初暗示这些PIK相关激酶可能能磷酸化脂质。但当检测PIK相关激酶底物专一性时，这些酶显示蛋白激酶的作用并已证明磷酸化磷脂酰肌醇。Hartley等，Cell，82849-856(1995)，报道纯化的样品在蛋白激酶试验中十分有活性，而不显示脂质激酶活性。鉴定的其它PIK相关激酶包括酿酒酵母的TEL1基因产物，它影响端粒长度[Greenwell等，Cell82823-829(1995)]，melanogaster果蝇的Mei 41+基因产物，它对G2关卡和减数分裂进行十分重要[Hari等，Cell82815-821(1995)]，小鼠的DNA-PK基因产物，它在免疫球蛋白重排和DNA双链断裂的加工中是重要的，还有在G1/S过渡中重要的FRAP基因产物[Brown，E.等，Nature，377441-446(1995)]。DNA-PK基因的突变会导致严重的复合免疫缺陷综合症(SCID)缺陷(Hartley et al.，同上)。
人类关卡功能所需的分子成分鲜为人知。通过分析人疾病综合症共济失调伴毛细血管扩张症(AT)已经识别了哺乳动物关卡机制的必需的一种分子成分。AT病人显示多种临床症状，包括对多种肿瘤的易感性。AT病人的成纤维细胞是辐射敏感的，并在IR处理后，不能产生细胞周期停滞，导致抗放射DNA合成现象。这使人联想起pombe裂殖酵母rad3缺陷，这样的细胞不能对DNA损伤适当地觉察或反应。有趣的是负责AT的基因座运动失调性毛细血管扩张症突变(ATM)基因最近在Savitsky等，Science，2681749-1753(1995)中描述，并且部分cDNA编码具有与rads+基因相似氨基酸的蛋白。Savitsky et al.，HumanMolecular Genetics，4(11)2025-2032(1995)描述编码全长ATM的cDNA的分离。rad3+酵母突变株和丧失有功能的ATM的哺乳动物细胞的放射敏感性增加提示这些蛋白可能包含关卡蛋白家族。
Kuerbitz等，Proc.Natl.Acad.Sci.USA，897492-7495(1992)证实抑癌基因p53是G1关卡和DNA损伤后观察到的细胞周期停滞需要的。照射细胞导致p53水平增加，使p53应答基因转录活化。一种p53诱导的靶点是WAF1基因产物(也叫P21，CIPl和sdil)。WAF1是叫做细胞周期蛋白依赖性激酶抑制蛋白的一类扩展之中的细胞周期调节物的一个成员。细胞周期蛋白依赖性激酶的活性控制细胞周期的运转。因而WAF1的转录活性在依赖于DNA损伤的p53的诱导和对细胞周期演进必需的激酶的抑制作用之间提供了直接的联系。见Elledge和Harper，CurrentOpinion in Cell Biology，6847-852(1994)。p53基因的突变是人类癌症中最常见的基因变化。例如，Baker等，Science，244217-221(1989)报道大约70％人结肠癌含有p53基因的缺失或突变拷贝。此外，Fearon等，Cell，61759-767(1990)报道乳腺癌、肺癌、膀胱癌和脑癌与p53基因所在的染色体17p区域的丢失有关。
目前，对哺乳动物细胞中G2关卡的分子成分相对知之甚少。咖啡因是一种取消G2关卡控制的化学实体。Russell等，Cancer Res.，551639-1642(1995)和Powell等，Cancer Res.，551643-1648(1995)报道其区别仅在于有或无有功能的p53存在的细胞系分析证明在那些缺少依赖于p53的G1关卡的细胞中，对IR有优先咖啡因增强的敏感性。因而，与含有完整G1关卡的细胞相比，缺乏G1和G2关卡的细胞中，潜在致死损伤到致死损伤的转变更多。
当某些细胞遭受依赖于DNA损伤的细胞周期停滞时，其它细胞似乎通过启动一种叫做细胞凋亡或程序性细胞死亡的内在自杀程序对DNA损伤起反应。决定哪种过程发生的因素不完全清楚。最近的工作证明p53在G1细胞周期过渡的调节和细胞凋亡中均起重要作用。Symonds等Cell，78703-711(1994)描述了作为抑制体内肿瘤生长和演进的依赖于p53的细胞凋亡。
高剂量的放射和化疗用于治疗肿瘤细胞以严重地损伤DNA致使细胞死亡。然而，即使具有p53基因突变的肿瘤细胞在G1关卡是缺损的，它们仍可修复放射或化疗引起的DNA损伤。本发明预期比如肿瘤细胞中G2关卡的抑制作用可能导致一种状态，在此状态中肿瘤细胞不能修复DNA损伤，因此使肿瘤细胞对DNA损伤剂敏感。含有完整G1和G2关卡的正常细胞在G2关卡特异性抑制剂存在下仍能修复DNA损伤。因而，先用G2关卡特异性抑制剂再用放射或化疗治疗肿瘤会增加细胞杀伤效果，从而减少所需的毒性DNA—损伤剂的剂量。
因此本领域存在鉴别参与细胞周期关卡的哺乳动物蛋白以开发与缺陷细胞周期关卡相关的人类疾病状态的疗法，并分离编码这些蛋白的基因的需要，它们可能对治疗有用或能开发治疗上有用的这些基因编码蛋白的调制剂。
发明概述本发明提供对细胞周期关卡必需的新人类PIK相关激酶，它在细胞周期的G2期对损伤的和非复制的DNA都有反应。
一方面，本发明提供编码细胞周期关卡PIK相关激酶MCCS1的纯化并分离的多核苷酸(如DNAs和RNAs，其编码链和非编码链)，以及编码其它细胞周期关卡PIK相关激酶的多核苷酸，这些多核苷酸与编码MCCS1激酶结构域的MCCS1多核苷酸区域表现出约50％、60％或65％的核苷酸一致性(SEQ ID NO30的MCCS1α核苷酸6579-7562，SEQ ID NO32的MCCS1β核苷酸6457-7440)。换句话说，MCCS1样PIK相关激酶与MCCS1激酶结构域(SEQ ID NO31的MCCS1α氨基酸2083-2410，或SEQ ID NO33的MCCS1β氨基酸2152-2480)显示了40％，45％或50％氨基酸一致性。本发明预期的多核苷酸包括基因组DNAs，RNAs，cDNAs和完全或部分化学合成的DNAs。本发明优选的多核苷酸包含在SEQ ID NO30列出的MCCS1αDNA序列，SEQ ID NO3列出的部分MCCS1βDNA序列，SEQ ID NO32列出的全长MCCS1βDNA序列和在严格条件下可与其非编码链杂交的或假如没有基因冗余，可与其非编码链杂交的DNA序列。典型的严格杂交条件如下在3×SSC，20mM NaPO4pH6.8中于65℃杂交，并在65℃用0.2×SSC洗。本领域技术人员已知这些条件的变化根据欲杂交序列的长度和GC核苷酸碱基含量而定。本领域的配方标准适合确定准确的杂交条件。见Sambrook et al.，9.47-9.51，分子克隆，冷泉港实验室出版，冷泉港，纽约(1989)。SEQ ID NO30的MCCS1αDNA保藏在美国典型培养物保藏中心(ATCC)，12301 Parklawn Drive，Rockville，Maryland 20852，1995年11月3日，作为大肠杆菌DH5α的质粒pBSHFB/HT2-27插入片段被指定ATCC登记号No 69951。SEQ ID NO32的MCCS1βDNA作为大肠杆菌中517质粒的插入片段于1995年11月7日保藏于ATCC，指定ATCC登记号No 69950。
本发明提供的DNA序列信息使通过已知技术如上述DNA/DNA杂交和聚合酶链反应(PCR)克隆，分离和鉴定编码相关分子的DNAs成为可能。作为一系列实施例，知道编码MCCS1的cDNA序列使得有可能通过编码该激酶的基因组DNA序列的DNA/DNA杂交分离和表达调控序列，如启动子，操纵子等。相似地，知道编码MCCS1β的部分cDNA序列便可能分离完整的cDNA。在严格条件下用本发明DNA序列进行的DNA/DNA杂交步骤同样期望使编码PIK相关激酶等位变种DNA分离；与PIK相关激酶同源的非人种的酶；以及其它具有一种或多种酶活性，或具有与MCCS1参加的细胞周期关卡通路中的成员或调节物相互作用能力的其它结构上相关的蛋白。本发明的多核苷酸当可检测标记后还可用于杂交试验以检测细胞合成MCCS1的能力。本发明提供的DNA序列信息还可通过同源重组或“剔除”策略[见Capecchi，Science，2441288-1292(1989)]使不能表达功能MCCS1或表达MCCS1变异体的啮齿动物的发育成为可能。这种啮齿动物作为体内研究MCCS1活性和MCCS1调制剂的模型是有用的。本发明的多核苷酸也许是对识别构成疾病状态基础的MCCS1基因座中基因变化有用的诊断方法基础。通过本发明还可得到通过那些通常表达同一基因的细胞调节的MCCS1表达的有关反义多核苷酸。
本发明也提供自主复制重组体构建物，如参入本发明多核苷酸的质粒和病毒DNA载体，特别是其中多核苷酸功能性与内源或异源表达控制DNA序列和转录终止子连接的载体。
根据本发明的另一方面，宿主细胞特别是单细胞的宿主细胞如原核和真核细胞，用本发明的DNAs以允许PIK相关激酶在此表达的方式被稳定转化或转染。本发明宿主细胞在MCCS1大规模生产的方法中十分有用，其中细胞生长于合适的培养基中，目的酶从细胞中或细胞所生长的培养基中分离。
仔细考虑了SEQ ID NO31，SEQ ID NO4或SEQ ID NO33中列出的部分或全部氨基酸序列的MCCS1产物。使用哺乳动物宿主细胞期望提供这些翻译后修饰(豆蔻酰化，糖基化，截短，脂质化和酪氨酸、丝氨酸或苏氨酸磷酸化)，因为可能是赋予本发明重组表达产物最佳生物活性所必需的。本发明的酶产物可以是全长多肽，片段或变体。变体包括MCCS1产物，其中一个或多个指定的(即天然编码的)氨基酸被缺失或替换，或其中加入一个或多个非指定氨基酸(1)不丧失对MCCS1特异的激酶活性；或(2)失去对MCCS1特异的激酶活性；或(3)失去与细胞周期关卡通路的成员或调节物相互作用的能力。MCCS1底物和与MCCS1相互作用的蛋白可用不同方法鉴别。
MCCS1的底物可通过在激酶活性试验中参入试验化合物而鉴定。MCCS1激酶悬于激酶缓冲液，在试验化合物(如酪蛋白，组蛋白H1或合适的底物肽)存在或不存在情况下温孵。通过放射自显影或液闪计数法测量由激酶转移到试验化合物上的磷酸摩尔数。将磷酸转移到试验化合物上表明试验化合物是激酶的底物。
相互作用蛋白可通过下列试验鉴定。
本发明预期的第一个试验是双杂交筛选。双杂交系统在酵母中建立[Chien等，Proc.Natl.Acad.Sci.USA，889578-9582(1991)]并基于激活报告基因的转录因子在体内的功能重建。特别地，编码与MCCS1相互作用的蛋白的多核苷酸通过如下分离用含有处于在启动子的控制下报告基因的DNA构建物转化或转染合适的宿主细胞，该启动子受具有DNA结合结构域和活化结构域的转录因子调节；在宿主细胞中表达编码部分或全部MCCS1与转录因子DNA结合结构域或活化结构域第一次融合物的第一个杂种DNA序列；在宿主细胞中表达编码部分或全部推定MCCS1结合蛋白与未参入第一次融合物的转录因子的DNA结合域或活化结构域第二次融合物的第二个杂种DNA序列文库；通过检测宿主细胞中报告基因产物的产生，而检测特定宿主细胞中MCCS1相互作用蛋白与MCCS1的结合；并从特定宿主细胞中分离编码相互作用蛋白的第二个杂交DNA序列。当前优选用于试验的是驱动报告基因表达的lexA启动子，lacZ报告基因是包含lexA DNA结合域和GAL4活性转换结构域的转录因子，和酵母宿主细胞。
鉴定与MCCS1相互作用蛋白的其它方法包含固定 MCCS1或一种试验蛋白，可监测地标记非固定化 结合伙伴，将结合伙伴一起温育并测定结合标记的量。结合标记指示试验蛋白与MCCS1的相互作用。
另一种确定MCCS1相互作用蛋白的方法包括在涂有(或浸渍)荧光剂的固体支持物上固定化MCCS1或其片段，用能激发荧光剂的化合物标记试验蛋白，将标记的试验蛋白与固定化的MCCS1接触，检测荧光剂的光发射，并鉴定作为导致荧光剂发光的试验蛋白的相互作用蛋白。或者，在试验中可固定化推定的相互作用蛋白并标记MCCS1。
本发明还包含抗体产物(如单克隆和多克隆抗体，单链抗体，嵌合抗体，嫁接CDR的抗体等)及其它对本发明MCCS1激酶特异的结合蛋白(如上面试验中确定的)。结合蛋白可用分离的天然或重组酶发生。反过来，结合蛋白对纯化重组体和天然产生的酶以及鉴定产生这种酶的细胞有用。本发明特别说明的单克隆抗体是由杂交瘤细胞系224C和224F产生的单克隆抗体，于1996年11月7日保藏于美国典型培养物保藏中心(ATCC)，12301 Parklawn Drive，Rockville，MD 20852并分别指定ATCC登记号Nos HB 12233和HB 12234。检测和定量细胞及流体中蛋白的方法可包含“三明治”方法形式中的单个或多种抗体物质。结合蛋白在调制(即封闭，抑制或刺激)酶/底物或酶/调制剂相互作用中也是明显有用的。对PIK相关激酶结合蛋白特异的抗独特型抗体也在考虑之中。
本发明考虑到MCCS1基因中的突变，它导致MCCS1基因产物正常功能的丧失，构成无G2细胞周期关卡参与的人疾病状态的基础。恢复MCCS1活性的基因疗法因而可能在治疗那些疾病中(如睾丸癌)指出。有功能的MCCS1基因向合适细胞的转运在体内或来自体内使用病毒载体(如腺病毒，相关腺病毒或逆转录病毒)或来自体内采用物理的DNA转移方法(如质脂体或化学处理)实现。基因治疗技术的叙述见Friedmann，Science，2441275-1281(1989)；Verma，Scientific；American68-84(1990)；Miller，Nature，35)455-460(1992)。换句话说，可以预期在其它人类疾病中阻碍MCCS1表达或抑制MCCS1活性的，对治疗疾病将是有用的。预期反义疗法或基因疗法可能用于MCCS1表达的负调节。能特异地与MCCS1表达控制序列或MCCS1 RNA结合的反义核酸(优选10-20碱基对寡核苷酸)被导入细胞(如通过病毒载体或例如质脂体的胶体分散系统)。反义核酸与细胞中MCCS1靶序列结合并阻止靶序列的转录或翻译。硫化磷的酯和甲基磷酸酯反义寡核苷酸被本发明特别期望于治疗使用。反义寡核苷酸可在其5′端再被多聚L-赖氨酸，转铁蛋白多聚赖氨酸或胆固醇部分修饰。
再者，假如MCCS1基因之外如p53基因的基因突变导致一种特殊的癌症形式，那么抑制MCCS1的转录或酶活及G2细胞周期关卡的试剂可用于使癌细胞对化疗或放疗更敏感。这种试剂的治疗价值基于这样一个事实，即目前的放疗或化疗在大多数情况下不能克服p53突变癌细胞来觉察和修正作为治疗结果的DNA损伤的能力。因而肿瘤细胞可简单地修复DNA损伤。所以本发明的调制剂可做为化疗、放疗的佐剂，或基本上直接作为化疗药。
调制MCCS1激酶活性的试剂可通过将试验化合物与从天然表达PIK相关激酶的细胞中免疫纯化的MCCS1，与表达该酶的重组原核或真核宿主细胞中得到的MCCS1或与纯化的MCCS1温育，然后测量被试化合物对MCCS1活性的影响来鉴定。PIK相关激酶的活性可通过测定该激酶从γ-32P-ATP向其本身(自身磷酸化)或外源性物质如脂质或蛋白转移32P-磷酸盐的摩尔数来测量。参入底物中磷酸盐的量通过液闪计数或放射自显影测定。被试化合物存在比不存在情况下向底物转移的磷酸盐的摩尔数增加表示该被试化合物为所述MCCS1激酶的激活剂。相反地，被试化合物存在比不存在情况下向底物转移的磷酸盐的摩尔数减少表示该调制剂为所述MCCS1激酶的抑制剂。另一方面，还期望了调节MCCS1和ATM或其中之一的试剂。调制MCCS1的试剂在上述ATM为进行磷酸化酶的激酶试验中筛选。
在当前的优选试验中，联接到琼脂糖珠的MCCS1特异抗体与从表达此激酶的宿主细胞制备的细胞裂解物温育。珠子洗去非特异结合的蛋白，再重悬于激酶缓冲液中。加Aγ-32P-ATP和合适的外源性底物如脂质或肽启动反应。激酶活性通过测定转移到激酶本身或加入底物的32P-磷酸盐的摩尔数测得。在优选的实施方案中，宿主细胞缺乏内源性MCCS1和/或ATM激酶活性。化合物调制MCCS1激酶活性的选择性可通过比较其对MCCS1及对其它已知PIK相关激酶的活性来评价。本发明的重组MCCS1产物与其它重组PIK相关激酶产物在一系列独立的试验中的组合提供了一个和开发选择性MCCS1调制剂的系统。
而且，组合文库、肽和肽模拟物、确定的化学实物、寡核苷酸和天然产物文库可用下面所述的实验筛选作为调制剂的活性。
例如，鉴定MCCS1激酶活性的调制剂的试验包括将激酶缓冲液中的MCCS1激酶样品与γ-32P-ATP和外源性激酶底物，有或没有被试化合物存在下一起温育，并测量转到底物上的磷酸盐摩尔数。被试化合物存在比不存在情况下转移到底物上的磷酸盐摩尔数增多，表示被试化合物为所述MCCS1激酶的激活剂。反之，被试化合物存在比不存在情况下转移到底物上的磷酸盐摩尔数减少，表示该调制剂为所述MCCS1激酶的抑制剂。
再者，鉴定调制MCCS1与其它蛋白相互作用的化合物的方法可包括用包含在启动子控制之下的报告基因的DNA构建物转化或转染合适的宿主细胞，该启动子受具有DNA结合域和活化域的转录因子调节；在宿主细胞中表达编码部分或全部MCCS1与转录因子DNA结合域或活化域第一次融合物的第一个杂种DNA序列；在宿主细胞中表达编码部分或全部与MCCS1相互作用蛋白和未参入第一次融合物的转录因子的DNA结合域或活化域的第二个杂种DNA序列；在有或没有被试化合物存在下，通过测定宿主细胞中报告基因产物的产量检测在特定宿主细胞中相互作用蛋白与MCCS1的结合，从而评价被试化合物对MCCS1和相互作用蛋白间相互作用的影响；并鉴定与无调控化合物时报告基因产物的产量相比改变了报告基因产物产量的被试化合物作为调控化合物。当前优选用于试验的是驱动报告基因表达的lexA启动子，lacZ报告基因，包含lexADNA结合域和GAL4反式激活结构域的转录因子，和酵母宿主细胞。
鉴定调制MCCS1和一种相互作用蛋白间相互作用的化合物的另一种方法包括固定化化MCCS1或一种天然MCCS1相互作用蛋白，可检测地标记未固定化的结合伙伴，将结合伙伴共同温育并测定被试化合物对标记结合量的影响，其中被试化合物存在比不存在情况下标记结合量减少表示被试化合物为MCCS1与蛋白相互作用的抑制剂。反之，被试化合物存在比不存在情况下标记结合量增加表示此推定调制剂为MCCS1与蛋白相互作用的激活剂。
本发明预期的鉴定调节MCCS1和一种相互作用蛋白间结合的化合物的另一种方法包括在涂布(或浸渍)荧光剂的固体支持物上固定化MCCS1或其片段，用能激发荧光剂的化合物标记相互作用蛋白，将固定化的MCCS1与标记的相互作用蛋白在有或无被试化合物存在下相接触，检测荧光剂的光发射，并鉴定与无被试化合物存在下相比影响荧光剂光发射的那些被试化合物作为调制化合物。或者，在试验中可固定化MCCS1相互作用蛋白并标记MCCS1。
本发明还提供用于鉴定调制MCCS1或ATM活性的化合物的基于细胞的互补实验。该方法包括与细胞中基因改变有关的表型特征的互补。例如，esrl-1基因改变导致酵母细胞对DNA损伤的细胞敏感性[Kato等，Nuc.Acids.Res.，22(15)3104-3112(1994)]。esrl-1细胞在用DNA损伤剂如离子化辐射或断裂剂处理后不能对DNA损伤觉察或适当地反应，基因改变细胞的表型特征通过在细胞中转化和表达MCCS1或ATM被互补。有或无被试化合物存在下转化的细胞用DNA损伤处理(如离子化辐射)并测量细胞对DNA损伤的敏感性。影响细胞对MCCS1和/或ATM的DNA损伤活性敏感性的试剂定为调制剂。
MCCS1的调制剂可能会影响其激酶活性、细胞中定位和/或其与细胞周期关卡通路成员的相互作用。MCCS1调制剂可配制于含有药用载体的组合物中。这种组合物还可包括化疗剂。指示剂量对体内MCCS1活性的调制会是足够的。选择的调制剂可包括如特异性与MCCS1或MCCS1核酸结合的多肽或肽，特异性与PIK相关激酶或PIK相关激酶核酸结合的寡核苷酸，和/或其它特异地与MCCS1或MCCS1核酸反应的非肽化合物(如分离或合成的有机分子)。本发明还期望影响野生型MCCS1酶活或细胞定位的MCCS1突变形式。目前优选的开发选择性调制剂的靶点的PIK相关激酶区域包括比如下面四个区域MCCS1α氨基末端效应物结构域(SEQ ID NO31的1-1081氨基酸)，MCCS1β氨基末端效应物结构域(SEQ ID NO＝33的1-1150氨基酸)，MCCS1αrad3+结构域(SEQ ID NO＝31的1082-2082氨基酸)，MCCS1βrad3+结构域(SEQ ID NO＝33的1151-2151氨基酸)，MCCS1αPIK结构域(SEQ ID NO＝31的2083-2410氨基酸)，和MCCS1βPIK结构域(SEQ ID NO＝33的2152-2480氨基酸)。
详细描述本发明由以下实施例来解释。实施例1详述编码MCCS1激酶cDNAs的分离。实施例2描述了人MCCS1基因在人染色体3的定位。MCCS1基因在大肠杆菌和昆虫细胞的重组表达分别在实施例3和4中描述。实施例4也介绍测定MCCS1激酶活性的试验。实施例5描述MCCS1-特异的多克隆和单克隆抗体的产生。实施例6报道来自小鼠睾丸的MCCS1激酶相关活性的免疫沉淀。实施例7检查MCCS1 mRNA在各种人组织和癌细胞株的表达。实施例8描述MCCS1 mRNA的分析和在小鼠睾丸中的蛋白表达。实施例9描述减数分裂细胞中MCCS1蛋白表达的分析。底物和MCCS1相互作用蛋白的测试在实施例10描述。实施例11描述调制剂和MCCS1激酶活性调制剂的测试。实施例12描述用于确定MCCS1和/或ATM调制剂的基于细胞的互补试验，以及实施例13描述ATM的激酶活性。
实施例1编码与PIK相关激酶MCCS1的cDNA通过系列PCR反应分离。
S.pombe rad3+(Hari等，见上)和酿酒酵母MEC1(Kato等，见上)的氨基酸序列的排列是七个简并性寡核苷酸的设计基础，该寡核苷酸在序列间编码(或互补于)最高同源性/最低简并性的区域并含有方便的剪切位点以便于扩增产物的克隆。然后寡核苷酸被用于基于PCR的试验中以分离相关的人序列。
开始，PCR扩增在从大鼠T-细胞的cDNA制品，人外周血单核细胞(PBMC)，以及酿酒酵母基因组DNA上进行。用五对寡核苷酸(oDH15a/oDH16，oDH15b/oDH16，oDH17a/oDH16，oDH15a/oDH17b，和oDH15b/oDH17b)进行初步扩增。寡核苷酸引物序列包括肌苷，并对简并的核苷酸位置以IUPAC命名列如下。
oDH15a(SEQ ID NO5)5′GCA GAC GGA TCC GGI WCI GAY GGI AAY HTI TAY 3′
oDH15b(SEQ ID NO6)5′GCA GAC GGA TCC GGI WCI GAY GGI AAY 3′oDH16(SEQ ID NO7)5′GCA GAC GAA TTC RCA RTY RAA RTC IAC RTG 3′oDH17a(SEQ ID NO8)5′GCA GAC GGA TCC AAR TTYCCI CCI RTI YTI TAY SAR TGG TT3′oDH17b(SEQ ID NO9)5′GCA GAC GAA TCC AAC CAYTSR TAI ARI AYI GGI GGR AAY TT 3′PCR在1×PCR缓冲液(Perkin Elmer Cetus，Emeryville，California)，2-3μMoDH引物，1.5mM MgCl2，200μMdNTPs，和0.5μlAmpli标记聚合酶的混合物中进行。反应在Perkin-Elmer Cetus Thermocycler480型仪器上完成，条件如下在94℃变性1分钟，在64℃退火2分钟，并于72℃延长1分钟进行三次循环。再用60℃退火温度循环三次，56℃退火循环三次，并以94℃变性1分钟，54℃退火2分钟和72℃延长1分钟进行30个循环结束。PCR产物在2或4％Tris乙酸EDTA(TAE)琼脂糖凝胶上分离，用溴化乙锭染色，通过UV荧光观察DNA产物。
从酵母基因组DNA，大鼠T-细胞cDNA，和人PBMC cDNA的初步扩增中，仅用酵母基因组DNA(oDH17a/oDH16)的单个反应给出可见的扩增产物，得到具有酿酒酵母MEC1区域的期望大小的在这些引物间的产物。因此完成了利用大鼠T-细胞和PBMC cDNA的oDH17a/oDH16扩增的进一步分析。为了除去寡核苷酸和可能干扰随后的PCR的“引物二聚体”，在再次PCR前纯化初步的反应。
采用“嵌套”PCR方法，扩增用引物对oDH18a/oDH16和oDH18b/oDH16在前述反应条件下以94℃变性1分钟，55℃退火1分钟和72℃延长30秒的循环重复30次。oDH18a和oDH18b寡核苷酸引物的序列包括肌苷，并对简并的核苷酸位置以IUPAC命名列如下。
oDH18a(SEQ ID NO10)5′GCA GAC GGA TCC YTI GGI YTI GGI GAY CGI CA 3′oDH18b(SEQ ID NO11)5′GCA GAC GGA TCC YTI GGI YTI GGI GAY AGR CA 3′在酵母基因组和人PBMC cDNA初步反应的再次扩增中可见大约90碱基对(bp)的产物(对这些引物期望大小的扩增产物)。在大鼠T-细胞cDNA初步反应的再次扩增中未见90bp产物，此反应不进一步分析。
除了大约90bp产物，也产生几个其它非特异带，尽管比初步反应用oDH17a/oDH16再次扩增时观察到的明显较少。在酵母基因组DNA初步反应的oDH18a/oDH16和oDH18b/oDH16再次扩增中出现了大约90bp产物，在人PBMC cDNA初步反应的再次扩增过程中仅oDH18a/oDH16反应产生了适当大小的片断。推测这反应了在人基因(比较引物oDH18a和oDH18b)中密码子的使用。来自人PMBC cDNA初步反应的oDH18a/oDH16再次扩增的大约90bp产物用胶纯化并亚克隆到pBluescript SKII+克隆载体(Stra标记ene，La Jolla，California)并测序。
被90bp产物编码序列的分析表明推断的氨基酸序列与酿酒酵母MEC1和S.pombe rad3+相似，但相互不是相同的。为了确定编码序列的较大区域和扩大序列比较，合成了一个非简并寡核苷酸，oDH23 5’GACGCAGAATTCACCAGTCAAAGAATCAAAGAG 3’(SEQ ID NO12)，用于附加的扩增反应。用oDH17a/oDH23对纯化的PBMC cDNA初步反应的再次扩增导致一个174bp扩增产物的产生。该片断然后被纯化，亚克隆并如上所述测序。概念翻译产物的计算机分析确定其与MEC1和rad3+的关系(相似但不相同)。该PCR片断然后被用作探针来筛选含有巨噬细胞cDNA的质粒文库，采用的杂交条件如下硝基纤维素膜用放射性标记的探针在3×SSC，5×Denhardt’s，0.1％十二烷基肌氨酸钠，20mM NaPO4pH6.8，100μg/ml单链鲑精DNA中于65℃温育18到24小时。在0.2×SSC，0.1％SDS中于65℃30分钟洗3次(更换洗涤缓冲液)。分离出四个阳性克隆，测定了每一个的核苷酸序列。四个序列的计算机分析证明它们是源自与来自S.pombe的rad3+基因同源的基因座的重叠克隆。克隆517(ATCC 69950)含有2.8kbp的插入并且其DNA和推断的氨基酸序列分别列于SEQ ID NOs3和4。此克隆包含编码氨基末端截短的870个氨基酸蛋白产物的读码框，该蛋白产物与rad3+的羧基端有39％相同。cDNA插入的蛋白产物被命名为MCCS1β。
克隆517的序列被用于设计寡核苷酸mo3 5’-CTACAGAGCCAAGGAG-3’(SEQ ID NO13)和mo6 5’-TCGAGCTATGCTAGTTGGGC-3’(SEQ ID NO14)，采用来自克隆517的胶纯化的EcoRI片断做为模板此寡核苷酸被用来产生探针。PCR条件如下50ng DNA片断，1×PCR缓冲液(Perkin-Elmer Cetus)，1.5mM MgCl2，200μM dATP，dGTP，和TTP，1μMdCTP，50μCiα32P-dCTP，每种寡核苷酸10ng/ml，1U AmpliTaq(Perkin-Elmer Cetus)。反应在480型Perkin-Elmer Cetus Thermocycler上进行，在94℃首次变性循环4分钟，随后是94℃15秒，60℃15秒，72℃30秒的20次循环。未掺入的核苷酸用Stra标记ene Nuc-trap Push柱除去。
由于Northern印记分析显示对应于克隆517mRNA的表达在睾丸最高，用产生自PCR的探针从人睾丸cDNA文库(Stra标记ene#939202)中筛选了一百万克隆并获得十一个克隆。选择两个最长的克隆，HT2和HT9进行分析。HT2含有4.7Kb的插入(对应于SEQ ID NO30的核苷酸2974并伸展到比SEQ ID NO1较远的下游)，HT9含有5485bp的插入(对应于SEQ ID NO30的核苷酸2152到7624)。核苷酸序列分析揭示在两个cDNA克隆的共同区域有一个在HT9位于核苷酸3233的T单一碱基对插入。该核苷酸插入造成预期的氨基酸读框迁移然后中止，认为是由逆转录酶在克隆HT9造成的错误。
为了分离含有附加2.5Kb的克隆，从三个附加cDNA文库中各筛选了一百万个克隆人胎脑cDNA文库(Stra标记ene#93206)，人心脏cDNA文库(Stra标记ene#93207)，以及人主动脉cDNA文库(ClontechLaboratories#HL1136a，Palo Alto，California)。HT9的大多数5’区的序列被用于设计和合成两个寡核苷酸，oHT9-1 5’-CCTAGTCCAGTAAAACTTGC-3’(SEQ ID NO15)和oTH9-4 5’-TTTGCGGCCCTTCCAATATC-3’(SEQ ID NO16)，它们被用于在产生上述探针的条件下产生一个317bp PCR探针。虽然从心脏或主动脉cDNA文库中没有分离到阳性克隆，但从胎脑文库中得到了两个阳性克隆。这些克隆之一，HFB2，包括一个cDNA4.5Kb插入片断，该片断包括大约2300bp的附加序列。HFB2插入片断对应于SEQ ID NO30的核苷酸1到3194。
从克隆HFB2，HT9和HT2构建了编码MCCS1α的复合cDNA。通过用限制酶KpnI和SalI消化HFB2产生一个含有复合克隆5’端的片断，用KpnI和NotI消化HT9产生一个包括复合克隆3’端的片断，然后将分离的片断连接到已用SalI和NotI消化的pBS SK-(Stra标记ene)载体上，使这三个克隆连接在一起。含有一个核苷酸插入的HT9片断区域被用含有克隆HT2的核苷酸3174到5282的EcoRV片断取代。最终的含有一个7621bp插入片断的质粒被命名为pBSHFB2HT2-27(ATCC69951)。DNA及推断的插入片断的氨基酸序列分别示于SEQ ID NOs1和2。cDNA的编码区域以在333核苷酸的ATG开始，以在7560核苷酸的终止密码子结束，预示一个2409氨基酸的编码序列和265kD的蛋白。cDNA插入片断的蛋白产物被命名为MCCS1α。在质粒pBSHFB2HT2-27(ATCC 69951)中插入片断的随后的序列分析揭示了在SEQ ID NO1的排序错误。改正的插入片断DNA和推断的氨基酸序列分别列于SEQ ID NOs23和24。质粒pBSHFB2HT2-27中插入片断的更进一步的序列分析揭示了在SEQ ID NO23的排序错误。在核苷酸位置6317(SEQ ID NO23)，错误地包括了一个“G”并且在位置6338和6339之间序列丢失了一个“A”。MCCS1α的改正序列在SEQ IDNOs30和31提供。
比较MCCS1α的预期氨基酸序列和从克隆517预期的MCCS1β的部分氨基酸序列揭示在MCCS1α产物中存在七十个氨基酸缺失。MCCS1β克隆517氨基酸序列对应于SEQ ID NO31的MCCS1α氨基酸1611到2410。在MCCS1α中七十个氨基酸的缺失(即此处应插入七十个氨基酸以产生等同于MCCS1β的产物)发生在SEQ ID NO31的氨基酸2065和2066之间，激酶结构域上游的十七个氨基酸。因为两种克隆都保持了可读框，cDNA克隆pBSHFB2HT2-27明显地产生自两者之一的已剪切mRNA。含有激酶结构域的羧基端区域在MCCS1α(SEQ IDNO31的氨基酸2083到2410)和MCCS1β克隆(SEQ ID NO4的氨基酸543到870)是等同的。
含有MCCS1β(具有七十个氨基酸插入片断)完全编码序列的复合克隆示于SEQ ID NO32。从该克隆推断的氨基酸序列示于SEQ IDNO33。此克隆是通过用HT2中所含有的HT2 3’端BstXI和NotI位点间的序列替换剪切第3229个核苷酸后面的BSTXI位点和pBSHFB2HT2-27(SEQ ID NO1)3’端多聚接头序列中NotI位点之间的序列而构建的。所以该克隆含有连接到与SEQ ID NO3(编码SEQ ID NO4的氨基酸1到870)克隆517的1到2610核苷酸相同序列的等同于SEQ ID NO1(编码SEQ ID NO2的氨基酸1到1609)的MCCS1α核苷酸1到5159的序列。如上指明的，随后的序列分析揭示在SEQ ID NO1的核苷酸1到5159中有错。改正的MCCS1βDNA和推断的包含出现于MCCS1αSEQID NOs23和24的相同改正的氨基酸序列列在SEQ ID NOs25和26。SEQ ID NO25克隆表示一个编码全长MCCS1β激酶的cDNA。SEQ IDNOs32和33给出包括纠正MCCS1α克隆重测序识别的错误的MCCS1β的其它序列。
MCCS1产物可以基于同其它PIK相关激酶的相似性被分成三个区域氨基端区域(SEQ ID NO31的MCCS1α氨基酸1到1081和SEQ IDNO33的MCCS1β氨基酸1到1150)，与rad3+相似的区域(SEQ IDNO31的MCCS1α氨基酸1082到2082和SEQ ID NO33的MCCS1β氨基酸1151到2151)以及包括激酶结构域的PIK区域(SEQ ID NO31的MCCS1α氨基酸2083到2410和SEQ ID NO33的MCCS1β氨基酸2152到2480)。氨基端区域和rad3+区域是调控区域，它调节酶的激酶活性并参与与相关蛋白的相互作用。
MCCS1α和MCCS1β的核苷酸及氨基酸序列与其它PIK相关及非PIK相关激酶序列的比较结果见表1。特别地，MCCS1α的3’末端(编码激酶区域的SEQ ID NO30的核苷酸6579到7562)，MCCS1β的3’末端(编码激酶区域的SEQ ID NO32的核苷酸1627到2379)，MCCS1α的rad3+区域(SEQ ID NO30的核苷酸3576到6578)，MCCS1β的rad3+区域(SEQ ID NO3的克隆517核苷酸1到1626)，与人TAM[Savitsky等，见上]，人DNA-PK[Huntley等，Cell，82849-856(1995)]，人FRAP[Brown等，见上]，人p110[Hud等，Mol.Cell.Biol.，13(12)7677-7688(1993)]，酿酒酵母MEC1[Weinert等，Genes Dev.，8(6)652-665(1994)]，S.pombe rad3+[Seatond等见上和Hari等，Cell，82815-821(1995)]和cAMP依赖的蛋白激酶(PKA)[Beebe等，Mol.Endocrinol，4(3)465-475(1990)]的类似区域做了比较。在表1中对每一种激酶的核苷酸的相同性百分比见顶行，氨基酸的相同性百分比见中间行，氨基酸的相似百分比(即包括相同的氨基酸和氨基酸的保守变异)见底行。在此使用的保守变异表示生物学相似残基。保守变异的实施例包括用疏水残基如异亮氨酸，缬氨酸，亮氨酸或蛋氨酸取代另一个，或用单极残基取代另一个，如用精氨酸取代赖氨酸，用谷氨酸取代天冬氨酸或用谷氨酰胺取代天冬酰胺等。在表中“ND”表示由于编码此激酶(既rad3+)的核苷酸序列不能公开得到或激酶(既FRAP，p110β或PKA)缺少被比较的特殊结构域，因此没有测定该值。
表1蛋白激酶 MCCS1α/MCCS1βMCCS1α MCCS1β激酶 rad3+ rad3+区域 区域 区域S.pombe rad3+ NDND ND5622 307246 53酿酒酵母 5142 44MECl 4521 246346 49人ATM 5041 413822 246046 47人DNA-PK 4339 432919 205345 49人FRAP 45ND ND37ND ND61ND ND人p110β45ND ND24ND ND54ND ND人PKA 39ND ND16ND ND39ND ND
实施例2通过基于PCR的试验MCCS1基因定位于染色体3。含有各种从NIGMS人基因突变体细胞贮藏所[Drwinga等，Genomics，16311-314(1993)]得到的人染色体板人/啮齿动物体细胞杂交体被用作模板。
基于MCCSlαcDNA序列的两个寡核苷酸引物oDH23(SEQ IDNO12)和oDH26 5’TGGTTTCTGAGAACATTCCCTGA3’(SEQ IDNO19)被用来扩增该基因的一部分。引物产生237bp PCR产物。PCR条件由25μl反应体积中50ng基因组DNA，每个引物0.5μg，200μMdNTPs，1.5mM MgCl2，1×PCR缓冲液(Perkin Elmer-Cetus)，以及1单位的AMpli标记聚合酶(Perkin Elmer-Cetus)组成。在480型Cetus Thermocycler上，样品变性4分钟，然后按变性，退火，分别45秒，30秒和45秒的延伸时间共循环35次。生成的5μl PCR产物在3％琼脂糖凝胶上电泳并用溴化乙锭染色。对应于人/啮齿动物染色体3的杂交体的DNA生成阳性扩增产物。
在第二套扩增反应中，相同的寡核苷酸引物用于把MCCS1基因亚定位到染色体3上特定区域。用于这些扩增的模板由从带有染色体3截短的病人得到的DNA样品组成[Leach等，Genomics，24549-556(1994)]。扩增如前面段落描述的那样进行。阳性扩增产物的形式将定位收缩于q21和q25.1之间。
实施例3编码PIK相关激酶MCCS1β羧基端部分的多核苷酸通过在大肠杆菌中重组技术表达。
构建两个大肠杆菌表达载体，表达针尖融合蛋白标记物表达/纯化系统(Promega，Madison，Wisconsin)中激酶的COOH末端423或571氨基酸残基。简要地说，编码激酶(SEQ ID NO3的核苷酸1339到2630或核苷酸898到2630)的羧基端部分的DNA序列在框架中被融合到一个来自propionibacterium shermanii转羧酶复合物的13kD肽的羧基末端。该区域在大肠杆菌中经过生物素化，从而提供了一个监测表达和融合蛋白纯化的方法。表达启动自针尖Xa3的tac启动子。融合蛋白表达用0.1M IPTG诱导并用链霉亲和素碱性磷酸酶如生产商描述的以假-Western格式证明。
实施例4用杆状病毒表达系统，MCCS1的重组体变型在酵母或在SF9昆虫细胞也可以表达。FRAP激酶已被表达，纯化并且在杆状病毒表达系统[Brown等，见上]表达后有酶促活性。
MCCS1的编码区在氨基端被融合到异源肽序列，如FLAG标记MDYKDDDDK(SEQ ID NO20)或一个六-组氨酸标记，并重新构建到适当的载体。一旦在昆虫细胞表达，识别FLAG标记(Eastman Kodak，Rochester，New york)的单克隆抗体用于纯化大量的FLAG-PIK相关激酶融合蛋白。感染的昆虫细胞温育48小时并在裂解缓冲液(25mM 2-甘油磷酸，50mM磷酸钠pH7.2，0.5％Triton-X100，2mMEGTA，25mM氟化钠，100μM钒酸盐，1mM PMSF，1μl/ml亮抑酶肽，1μl/ml胃酶抑制剂，1mM苯甲脒，和2mM DTT)中裂解。表达的FLAG融合蛋白通过含有抗FLAG抗体M2亲和树脂(Eastman Kodak)的柱子纯化。该柱用20倍柱体积的裂解缓冲液冲洗，然后5倍柱体积的0.5M氯化锂，50mM Tris pH7.6，1mM DTT洗，然后用0.1M甘氨酸pH3.0随后立即中和或通过用FLAG肽竞争洗脱来洗脱。对六-组氨酸标记的蛋白，Ni-NTA琼脂糖(Qiagen)被用于蛋白纯化。
专利申请U.S.S.N.08/558,666申请后不久，Antony M.Carr和合作者(个人通讯)描述了鉴定为ATR的基因。基于ATR和MCCS1之间氨基酸序列的比较，ATR看来好象编码与MCCS1相同或密切相关蛋白。DNA和ATR的推断氨基酸序列分别示于SEQ ID NOs28和29。ATR和MCCS1β之间的序列差异如下。ATR在N-末端包括附加的98个氨基酸残基。在核苷酸位置1284(SEQ ID NO32)有一个保守碱基从MCCS1β的“A”变为ATR的“T”，并且在核苷酸位置4176有一个附加的保守碱基从MCCS1β的“C”变为ATR的“T”。
FLAG标记物融合在缺少开始66个ATR氨基酸的截短的ATR分子的氨基末端。FLAG标记物通过PCR如下加入。寡聚物FLAG-ATR(5′-CGGGATCCGCCATGGACTACAAGGACGATGACAAGATGTTGCTTGATTTC-3′)，和HFB24(5′CTTAAGCCGCATGAGCACACCGTC-3′)被用于下列PCR反应100ng pcDNAATR(从Antony M.Carr得到)做为模板；1×PCR缓冲液(Perkin-Elmer Cetus)；1.5mM MgCl2，dATP，dGTP，dCTP和TTP各200μM，每个引物10ng/μl；1UAmpli标记(Perkin-Elmer Cetus)。反应在94℃变性4分钟，然后进行94℃30秒、60℃30秒和72℃30秒循环30次。得到的约800bp PCR产物用BamH1和Nhe1消化，连接到哺乳动物ATR表达质粒pcDNAAT用BamH1和BstXI消化得到的10kb片断以及2.5kbBstXI到NheI片断含有的编码ATR序列的剩余部分。序列分析证实加上了FLAG标记。该质粒含有的插入片断然后用于构建能表达FLAG标记的ATR截短物的杆状病毒表达质粒。来自pDTMATR，BamH1到BstXl片断含有的5’端ATR和BstXI到SalI片断含有的3’ATR连接到已用BamHI和SalI消化的杆状病毒表达载体pFB(Gibco.BRL)上。此质粒命名为pFMBCCSβFLAG。
ATR的全部编码区氨基末端用PCR融合到六个组氨酸标记上。多核苷酸MCCS6his(5′-CGGGATCCAGCATGCATCACCATCACCATCACATGGGGGAACATGGGC-3.)和FrplR(″5′-CATGACCACTGGCCATTCCACACG-3′)用于PCR反应以向编码ATR氨基端的序列加六个组氨酸标记。PCR条件如下100ng PstA 12ATR(从Antony M.Carr得到)做为模板；1×PCR缓冲液(Perkin-Elmer Cetus)；1.5mM MgCl2，dATP，dGTP，dCTP和TTP各200μM，每个引物10ng/μl；1U Ampli标记(Perkin-Elmer Cetus)。反应在94℃变性4分钟，然后进行94℃30秒、60℃30秒和72℃30秒循环25次。约800bp PCR产物用BamH1和Msc1消化，连接到另外两个片断用BamH1和BstXI消化pcDNAATR得到的10kb片断和含有ATR编码序列的剩余部分的大约3kb MscI到BstXI片断。序列分析证实加入了六个组氨酸标记得到的编码以六个组氨酸标记的全长ATR分子的质粒被命名为pcDNA6hisATR。
为了构建表达ATR全部编码序列的杆状病毒表达质粒，pFMBCCSβFLAG的1.2kb BamHI到AgeI片断连接到pcDAN6hisATR的BamI到AgeI片断得到的称作pFB/HisX6MCCS-1质粒转化到大肠杆菌菌株DH5α(Gibco/BRL)用于筛选重组体。该质粒用Promega“Wizard”mini-prep试剂盒纯化，然后用Gibco/BRL描述的Cellfectin方法转化到大肠杆菌αSF9细胞(Invitrogen)中。
转染后48小时收获SF9细胞沉淀和转染细胞产生的杆状病毒。该病毒在4℃含有10％FBS，青链霉素和庆大霉素的Grace’s完全培养基中储存。该病毒样品用来制造高滴度(P2)病毒储液。此P2病毒储液用于感染50ml SF9细胞培养物。感染后48小时收集细胞并以低速离心，在不裂解的情况下沉淀细胞。裂解前细胞沉淀在-20℃储存24小时。细胞在5ml裂解缓冲液(50mM Tris，pH8.0；500mM NaCl；1％NP40；100μMPMSF)中裂解。用抗AgDH2的多克隆抗体做探针通过免疫印记证实ATR的表达。FBHisX6 ATR杆状病毒产生一种约300kDa蛋白，它与抗AgDH2抗体免疫反应并与小鼠睾丸细胞提取物中的蛋白共迁移。
P2病毒储液还用于感染两升SF9细胞培养物。感染后48小时收集细胞，低速离心，在不裂解的情况下沉淀细胞并储存于-20℃。100ml此培养物的细胞沉淀在7.5ml裂解缓冲液(50mM磷酸钠ph7.2；0.5％NP40；10mM咪唑，25mM氟化钠，100μM Na3VO4；0.5mMAEBSF；1μg/ml亮抑酶肽；1μg/ml抑胃酶肽A)中裂解并在冰上保温15分钟。裂解物以10000×g离心30分钟。去掉上清液，由于核破裂得到的裂解物中DNA通过20号针头抽吸剪切。颗粒物质通过0.8微孔滤膜和0.2微孔滤膜过滤除去。澄清的裂解物调至含5mM β-巯基乙醇和0.4M NaCl。在澄清裂解物上样前一个1ml Ni-NTA-琼脂糖柱(Qiagen)用缓冲液A(0.4M NaCl；5mMβ-巯基乙醇；0.1％Triton X-100；50mM磷酸钠，10mM咪唑；25mM氟化钠，100μM Na3VO4；0.5mMAEBSF；1μg/ml亮抑酶肽；1μg/ml抑胃酶肽A)平衡。样品以0.25ml/min的流速载样，5ml缓冲液A洗，然后以10ml在缓冲液A中50到500mM咪唑的梯度洗脱。按0.5ml部分收集，并按下面方法试验激酶活性。每部分的10c在激酶缓冲液，10μCi32PγATP，10μM ATP，以及5μg底物PHAS-1(Stra标记ena)并在37℃温育20分钟。反应液然后点到磷酸纤维素离心柱上，以2500×g离心，用0.5ml 75mM磷酸洗两次并用0.5ml无水乙醇洗一次。磷酸纤维素盘然后转移到闪烁管中，记录每分钟掺入到PHAS-1蛋白中的数目。发现4到9部分对PHAS-1有活性，免疫印迹分析证实ATR也存在于相同的部分中。
编码质粒DNA的MCCS1转化到一个esr1-1二倍体酵母菌株(Mataleu2-1 his4-4 can1 ura3 cyh2 ade6 ade2 esr1-1/MAT a leu2-27 his4 trp1met2 ade2 esr1-1)，细胞在含有半乳糖或葡萄糖的培养基中生长到对数中期。细胞沉淀等所有步骤在4℃进行。细胞糊重悬于缓冲液(20mMTris pH8.0，300mM NaCl，10％甘油，0.1mM PMSF，0.25mg/ml胃酶抑制剂，亮抑酶肽，和抑蛋白酶肽)中并在弗氏亚碎器中或用玻璃珠裂解。裂解用显微镜核实，随后低速(10K)离心和高速(100K)离心，上清液上样到预先用1×缓冲液洗过的1.5ml Ni-NTA琼脂糖(Qiagen，Inc.，chatsworth，CA)柱上。柱子用6倍柱体积的缓冲液洗。该柱子分步用含10mM，50mM，100mM和250mM咪唑的缓冲液各8ml洗脱。分部收集并用每个洗脱峰的15μl进行Western分析。激酶活性如上描述测定。
实施例5对MCCS1特异的多克隆和单克隆抗体通过本领域标准技术产生。
两种不同的细菌表达质粒，pGEX1-MEC和pGEX3-MEC，用于做为谷胱甘肽S转移酶(GST)羧基端融合物的MCCS1多肽部分重组产物的构建。两种质粒pGEX1-MEC和pGEX3-MEC分别用于在标准免疫接种方法中使用的抗原抗原AgDH-2和AgDH-3的产生。pGEX1-MEC含有编码融合到pGEX1载体(Pharmacia Biotech，Milwaukee，Wisconsin)中GST的SEQ ID NO4的566到879氨基酸残基的EcoRI片断；pGEX3-MEC含有编码融合到pGEX3载体(Pharmacia Biotech)中GST的SEQ ID NO4的118到576氨基酸残基的EcoRI片断。pGEXtac启动子用0.1mM 1PTG诱导导致处于不溶形式(包含体)的每种融合蛋白的高水平表达。诱导的培养基用弗氏亚碎器裂解后，AgDH-2和AgDH-3提取物经含有0.1M NaCl，0.01M Tris pH7.5，和0.001MEDTA(STE)的35％葡萄糖溶液离心。然后沉淀液洗两次并重悬于STE中。
为了在兔中产生单克隆抗血清，AgDH-2和AgDH-3进一步用制备SDS聚丙烯酰胺凝胶电泳纯化，并从胶片上电洗脱出每个抗原。雌性新西兰白兔的初级免疫接种是用与弗氏完全佐剂混合的每种抗原200μg注射到随机的多个部位。随后的免疫接种是用与弗氏非完全佐剂混合的100μg抗原在约21天间隔进行，测试血液在接种3，4和5次后抽取。人睾丸组织提取物的Western印记分析说明对免疫中大约270kD蛋白的抗体有活性，而非免疫前抗血清。另外，免疫血清显示对实施例3描述的MCCS1针尖融合蛋白的活性，提供了MCCS1特异抗体产生的事实。
MCCS1特异抗体按如下方法纯化。制备的AgDH-2和AgDH-3包含体偶合到溴化氰(CNBr)活化的琼脂糖凝胶(Pharmacia，Alameda，CA)。2mg抗原溶解在1％SDS(终体积45ml)并在偶联缓冲液(0.1MNaHCO3/0.1％SDS)中透析过夜。在用CNBr琼脂糖温育前加入0.5ml 5MNaCl到每一个制备抗原中。0.4gm冻干的CNBr琼脂糖(每个抗原)重悬于1mM Hcl并在scintered玻璃漏斗中用250ml 1mM HCl洗，HCl在15分钟内分几部分加入。然后HCl洗过的CNBr琼脂糖转移到一个15ml揿帽管中并用5ml偶联缓冲液冲洗二次。透析过的抗原样品加入到洗过的琼脂糖中，然后在缓慢旋转轮上室温温育1.5小时。琼脂糖用5ml偶联缓冲液洗一次，用10ml 0.1M Tris pH8.0洗一次，然后在10ml 0.1M TrispH8.0中室温温育2小时以封闭树脂上的任何剩余活性基团。用SDS-PAGE分析判断偶联效率为60-80％。抗原柱然后用15ml 6M盐酸胍(除去未偶联抗原)，25ml缓冲液A(30mM Tris pH7.4)，15ml缓冲液B(4.5M MgCl2/1mg/ml BSA/50mM Tris pH7.4)，然后用50ml缓冲液A洗。30ml来自已免疫动物(用AgDH-3免疫的兔4747和用AgDH-2免疫的兔4779)的兔血清经3小时流过此适当的抗原柱。柱子然后用20ml缓冲液A，40ml 1M盐酸胍洗，再用另外20ml缓冲液A平衡。然后用10ml缓冲液B从抗原柱上洗脱下抗-AgDH-3和抗-AgDH-2抗体。按1ml部分收集，含IgG的部分合并，在1L磷酸盐缓中液(PBS)中透析3小时，然后在1L含35％甘油的PBS中透析过夜。
通过用EDC按生产商(Pierce)所描述的把15-氨基酸肽(残基1359-1373)偶联到匙孔血蓝蛋白上，然后把偶联的免疫原注射到兔中来产生抗人ATM蛋白的抗肽抗体。随后用等量体积的饱和氯化铵重悬并在PBS中透析，抗体首先从血清(#6076)中沉淀出来。使用按生产商描述的通过抗体肽偶联到CNBr活化的琼脂糖(Pharmacia)制备的肽柱实现亲和纯化。抗体然后结合到肽柱上并用2命令KCl-PBS洗。用20ml Sm NaI(在1mM硫代硫酸钠中)实现洗脱，洗脱液立即在PBS中透析。
为了生成单克隆抗体，雌性Balb/c小鼠用50μg AgDH-2或AgDH-3免疫。另外的小鼠用已经与等摩尔比的mAb 61F3B结合的25到50μgAgDH-2或AgDH-3免疫，mAb 61F3B是对GST有特异活性的单克隆抗体。第三组小鼠用含AgDH-2或AgDH-3的聚丙烯酰胺凝胶片免疫。每组小鼠的免疫原在弗氏完全佐剂中制备，然后间隔约21天进行攻击(弗氏非完全佐剂中25μg抗原)。产生单克隆抗体细胞株按如下方法分离。简要地通过在补充以2mM L-谷氨酰胺，1mM丙酮酸钠，100单位/ml青霉素，以及100μg/ml链霉素(RPMI)(Gibco，Cahada)的无血清RPMI1640中研磨免疫小鼠脾，形成单细胞悬液。该细胞悬液通过无菌70目Nitex细胞滤器(Bocton Dickinson，Parsippang，new Jersey)过滤，在200g离心5分钟，洗两次，在20ml无血清RPMI中重新悬浮沉淀。从三个新生Balb/c小鼠取出的胸腺细胞以此方法制备。
在融合前三天用含11％胎牛血清(FBS)(Hyclone Laboratories，Inc.，Logan，Utah)的RPMI保持在对数期的NS-1骨髓瘤细胞，在200g离心5分钟，象前面描述的洗沉淀二次。洗后，每种细胞悬液在无血清RPMI中制成终体积10ml，取10μl按10∶100稀释。取每种稀释液20μl，与20μl含0.4％台盼蓝染色剂的0.85％盐水(Gibco)混合，在血细胞计数计上计数。
2×108脾细胞与4×107NS-1细胞结合，离心，吸出上清液。轻拍试管取出细胞沉淀，并在1分钟过程内搅拌加入2ml 37℃PEG 1500(在75mM Hepes，pH8.0中50％)(Boehringer Mannheim)，随后在7分钟内加入14ml无血清RPMI。另外加入16mlRPMI，细胞在200g离心10分钟。倾去上清液后沉淀重悬于含15％FBS，100μM次黄嘌呤钠，0.4μM氨基蝶呤，16μM胸苷(HAT)(Gibco)，25单位/ml IL-6(Mallinckrodt，Folerost，Pennsylvania)，和1.5×106胸腺细胞/ml的200ml RPMI中。板中的细胞在融合和筛选之间用18G针头从每孔吸出约一半培养基并补充上述含10单位/ml IL-6和无胸腺细胞的接种培养基，进行3到4次。
当细胞生长达到60-80％融合度时(7-9天)，通过用AgDH2对AgDH3的ELISA筛选融合物。Immunlon4板(Dynatech，Cambridge，MA)用含100ng/孔蛋白的30mM碳酸盐缓冲液，pH9.6于4℃覆盖过夜。板用含100μg/孔0.5％鱼皮明胶的PBS在37℃封闭1小时，用PBS洗三次，加入0.05％Tween 20(PBST)和50μl培养基上清液。37℃温育30分钟后，如上所述洗涤，加入在PBST中1∶10,000稀释的偶联山羊抗-小鼠IgG(fc)(Jackson ImmunoResearch，West Grove，PA)的辣根过氧化物酶50μl。板如上所述温育，用PBST洗四次，加入由100μg/ml四甲基联苯胺和含0.15μl/ml H2O2的100mM乙酸钠，pH5.5组成的底物。在5-10分钟加入50μl 15％H2SO4中止颜色反应。在板读数器上读取A490值。
在ELISA中呈阳性的杂交瘤的53个库筛选与来自小鼠睾丸细胞裂解物的MCCS免疫印迹和免疫沉淀的能力。用小鼠睾丸提取物的免疫印迹分析在实施例6中描述。免疫沉淀完成如下。走6％聚丙烯酰胺凝胶并在192mM甘氨酸，25mM Tris碱，0.1％SDS，20％甲醇中转移到Immobilon-PVDF膜上，然后在5％脱脂奶粉，20mM Tris pH7.5，100mMNaCl，0.1％Tween 20中封闭1小时，并切成适当数目的细条。初级抗体(孔上清液)在上面的封闭液中稀释并室温温育1小时，在无奶封闭液中洗四次，在山羊抗小鼠IgG(H+L)HRP(BioRad #170-6516)中温育，再在无奶封闭液洗，转移到NEN Renaissance ECL试剂并显影5分钟。
免疫沉淀如下进行。50μl杂交瘤上清液于按实施例6所述制备的300μg睾丸细胞裂解物在冰上温育1小时。加入30μl与兔抗-小鼠桥联抗体(5μg/反应)(Pierce)预先结合的蛋白A琼脂糖的50％匀浆，在4℃摇动温育。免疫复合物在裂解缓冲液中洗三次，抗原/抗体复合物通过在SDS样品缓冲液(2％SDS，20mM Tris pH6.8，20％甘油，0.001％溴酚蓝)中煮沸洗脱。生成的上清液在6％SDS聚丙烯酰胺凝胶上分离，转移到Immobilon-PVDE(Millipore)膜上并用亲和纯化的兔抗-AgDH2多克隆抗血清进行免疫印迹。克隆了四个杂交瘤并如实施例6所述在免疫印迹、免疫沉淀和免疫沉淀/激酶试验中显示其特性。这四个杂交瘤细胞株被指定为224B、224C(ATCC HB 12233)，244F(ATCCHB 12234)和224G。所有四个单克隆抗体经免疫印迹和免疫沉淀识别MCCS1。
实施例6MCCS1相关蛋白激酶活性用实施例5所述的MCCS1特异多克隆抗体免疫沉淀。
提取物从由Balb/c小鼠分离的新鲜睾丸组织制备。剪碎的睾丸在裂解液(50mM NaPO4，pH7.2；0.5％TritonX-100；2mM EDTA；2mM EGTA；25mM NaF；25mM 2-甘油磷酸盐；1mM苯甲基氟磺酸[PMSF]；1μg/ml亮抑酶肽；1μg/ml胃酶抑制剂A；2mM DTT)中于冰上用紧密配合的dounce匀浆器匀浆10-15下，再在冰上保温30分钟。在TL-100台式超速离心机(Beckman)，裂解物在13,000×g rpm上于4℃离心10分钟以除去未破碎的细胞和其它不溶物。等分的细胞裂解物在液N2中快速冷冻并在-70℃保存。500μg睾丸提取物与5μg亲和纯化的抗-AgDH-2多克隆抗体或5μg纯化的兔IgG(Zymed，So.San Francisco，CA)在1ml裂解缓冲液中在冰上于衡量离心管内温育1小时。30μl蛋白A琼脂糖玻璃柱(Repligen，Cambridge，MA)(已在裂解缓冲液中洗过)加入到提取物中，然后在摇动平台上于4℃温育另外的30分钟。免疫复合物/蛋白A琼脂糖玻璃柱用1ml裂解缓冲液洗四次，用1ml激酶缓冲液(25mMHepes pH7.7；50mM NaCl；10mM MgCl2；0.1％NP-40；2％甘油；1mMDTT)洗一次，然后含有10μCi ATP[50 Ci/mmol]的20μl激酶缓冲液中温育20分钟。在用6％聚丙烯酰胺凝胶分离前用20μl 2×SDS样品缓冲液并加热到100℃停止激酶反应。凝胶在20％甲醇/7％乙酸中固定化，放射自显影前在Whatman 3MM纸上干燥。尽管在控制免疫沉淀中很少或没有明显的磷酸化作用，但使用抗-AgDH-2抗体的免疫沉淀在约300kD和约18kD处含有两条主要的磷酸化条带。另外，有几个小的磷酸化产物，包括一个与MCCS1蛋白本身共迁移的产物，如由Western印迹分析所证实的(见实施例8对Western印迹的描述)。约300kD蛋白的磷氨基分析证实磷酸丝氨酸残基的存在。5μg AgDH-2(而非AgDH-3)的加入显著地减少或消除在免疫沉淀中发现的MCCS1相关激酶活性。
实施例7MCCS1在各种人组织中的表达形式由Northern印迹杂交检查。
含有来自各种人组织源的大小分级的含polyA+RNA 2μg的尼龙膜从Clontech Laboratories，Inc.得到，严格遵守生产商提供的杂交方法，只是为了减少与相关序列的交叉杂交的可能性，最终的洗脱是在55℃进行，而非50℃。使用PCR产生的32P标记DNA杂交探针。编码MCCS1α的COOH末端30％的DNA被用作模板在32P-dCTP存在下来扩增1.3kb片断，使用的引物是279-3 5’TGGATGATGACAGCTGTGTC3’(SEQ IDNO21)和279-6 5’TGTAGTCGCTGCTCAATGTC3’(SEQ ID NO22)。
Northern印迹的结果显示MCCS1在广泛的人组织中做为一个约9kbmRNA被表达。睾丸组织含有高水平的MCCS1 mRNA，尽管转录在小肠，卵巢，前列腺，胸腺，脾，心脏，外周血淋巴细胞，结肠，脑，胎盘，骨骼肌肉，肾和胰中也被表达。
MCCS1 mRNA在人肿瘤细胞株的表达也是用从Clonetech得到的人肿瘤细胞株RNA印迹检测。RNA印迹含有来自细胞株HL-60(早幼粒白血病)，Hela(子宫癌)，K-562(慢性成髓白血病)，MOLT-4(成淋巴细胞白血病)，Raji(布氏淋巴瘤)，SW480(结肠腺癌)，A549(肺癌)和G361(黑色素瘤)的RNA。Northern印迹分析按生产商指导的完成，杂交用MCCS1部分克隆HFB2的2.0kb Kpnl-Sall片断在65℃完成。在HL-60，Hela，K-562，Raji，Sw480和G361细胞株观察到表达，在G361细胞株发生最高水平的表达。在MOLT-4和A549细胞株中观察到可测得但低水平的表达。
实施例8正常和辐射的小鼠睾丸和小鼠胚胎中MCCS1 mRNA和蛋白的表达通过原位杂交、免疫染色和/或免疫印迹检查。原位杂交从雄性Balb/c小鼠收获正常和辐照小鼠睾丸。组织切成6μm厚度的切片，放到Superfrost Plus(VWR Scientific)载玻片上，室温空气干燥过夜。如不立即使用，切片在-70℃保存。组织切片在含4％低聚甲醛的PBS中于4℃固定化20分钟，在4℃每一级(70％，95％，100％乙醇)脱水1分钟，然后室温空气干燥30分钟。载玻片在0.25％(v/v)乙酸酐(Sigma)/0.1M三乙醇胺pH8.0溶液中搅动下室温酰化10分钟，搅动下在0.2×SSC中室温冲洗10分钟，并如上所述脱水和空气干燥。组织与来自小鼠MCC S1 DNA并用地高辛标记的单链mRNA进行原位杂交，该mRNA通过体外RNA转录掺入地高辛-UTP(Boehringermannheim)。标记的核糖探针(见SEQ ID NO27中的序列)(1μg/切片)和焦磷酸二乙酯(depc)处理的水加入到杂交缓冲液，终浓度是50％甲醇胺，0.3M NaCl，20mM Tris pH7.5，10％葡聚糖磷酸酯，1×Denhard溶液，100mM二硫苏糖醇(DTT)和5mM EDTA，无RNase 22×22盖玻片覆盖。在切片和探针溶液中的mRNA通过在炉中加热载玻片到85℃10分钟来变性。杂交在50℃过夜(12-16小时)完成。
杂交后，切片在4×SSC/10mM DTT中室温洗1小时，然后在50％甲醇胺/2×SSC/10 mM DTT中50℃洗30分钟，在500mM NaCl，10mM Tris-HCl，1mM EDTA，pH7.5(NTE缓冲液)的溶液中37℃洗30分钟，在含10μg/ml RNase A(Boehringer Mannheim)的NTE缓冲液浴中37℃洗30分钟，在NTE缓冲液中于37℃洗15分钟，在2×SSC中室温洗15分钟，在0.1×SSC中室温洗15分钟，在100mM Tris-HCl，150mM NaCl，pH7.5(缓冲液1)中室温洗2分钟。为探测标记的核酸探针，切片在5％正常羊血清(Harlan Bioproducts for Science，Indianapolis，IN)和含0.3％Triton X-100(Sigma)的缓冲液1的溶液中于室温，温和搅动下封闭30分钟，随后150μl/切片羊α地高辛-金偶联物(GoldmarkBiologicals，Philipburg，Pa)用于该组织并在室温温育2小时。载玻片然后在缓冲液1中5分钟洗三次，在无菌去离子水中3分钟洗5次，过量液体从载玻片上吸干，银增强和始发溶液(Goldmark Biologicals)各2滴加入到每个玻片上。让该化学反应室温进行23分钟，然后切片在无菌去离子水中彻底冲洗，在Nuclear Fast Red(载体)中对染，再在无菌去离子水中冲洗，室温空气干燥过夜并用Cytoseal 60(VWR)制成标本。
在正常和照射的小鼠二者的睾丸观察到精原细胞和精母细胞的细胞质中的信号。照射的睾丸中表达水平未升高超过正常睾丸。免疫染色来自正常的雄性Balb/c小鼠的睾丸组织以6μm厚度切片，放到Superfrost Plus(VWR Scientific)载玻片上，室温空气干燥过夜。如不立即使用，切片在-70℃保存。切片在室温于冷(4℃)丙酮中固定化10分钟；一旦载玻片从丙酮中取出，让溶剂从切片上挥发。每一个组织切片用150μl在1×TBS中含30％正常大鼠血清(Harlan Bioproducts)，5％正常山羊血清(Vector Laboratories)和1％牛血清白蛋白(Sigma)的溶液室温封闭30分钟。封闭后，从切片小心吸干溶液，来自相同兔的抗AgDH-3和AgDH-2单克隆抗体和免疫前血清在封闭溶液中按1∶50和1∶100稀释，并取100μl到每一个组织切片，在37℃温育30分钟。从切片上小心地吸干抗体溶液，未结合的抗体通过在1×TBS洗载玻片三次，每次5分钟，从切片除去。过量的TBS从载玻片上吸去，100μl存在于Elite Rabbit IgG VectastainABC试剂盒(Vector)中，根据产品插入片断制备的生物素化的山羊抗兔抗体加入到每一个切片并在37℃温育15分钟。温育后，载玻片在1×PBS中洗两次，每次5分钟。随后，100μl在含有5％正常大鼠血清和1％BSA的溶液中1∶100稀释的链亲和素-金偶联物(Goldmark Biologicals)加入到每一个切片中，室温温育1小时。载玻片然后在1×TBS中洗3次，每次5分钟，100μl含1％戊二醛的TBS缓冲液室温加入到载玻片上5分钟。然后载玻片在TBA中洗3次，每次5分钟，再在无菌去离子水中洗4次每次3分钟。过量的液体从每个载玻片上吸干，银增强和始发溶液(Goldmark biologicals)各两滴加到每个切片上。让该化学反应室温进行13分钟，然后切片在无菌去离子水中彻底淋洗，在Nuclear Fast Red(Vector)中对染，再在无菌去离子水中冲洗，室温空气干燥过夜并用Cytosea160(VWR)制成标本。
在带有两个多克隆抗体的精原细胞和初级精母细胞检测到了信号，从相同动物的免疫前血清未检测到信号。免疫印迹新获得的小鼠睾丸用剃刀片在冷PBS中切碎，用松散结合的dounce匀浆器产生细胞悬液。然后该细胞悬液用等体积的2×SDS样品缓冲液煮沸。每个提取物的50μg等份在6％聚丙烯酰胺凝胶上分离，转移到Immobilon膜(Millipore，Bedford，MA)上并用实施例5中亲和纯化的抗体，以及HRP缀合的山羊抗兔二代抗体和Renaissance增强的化学发光试剂盒分析抗MCCS1反应性。从新鲜小鼠睾丸制备的提取物含有一种由亲和纯化的抗血清识别的高分子量种类(约294kD)。两种免疫前血清都未见到对此蛋白的活性。重要地，从每一个亲和纯化血清获得的信号在抗体与对应免疫原的预温育后是被特异封闭的。
总的来说，在精原细胞和处于减数分裂早期阶段的初级精母细胞中的小鼠睾丸检测到高水平的MCCS1 mRNA和蛋白。这暗示MCCS1在减数分裂细胞分裂中起重要的作用。减数分裂是细胞分裂的特殊形式，它在较高等真核生物中产生生殖细胞。有两个减数分裂的主要特征使其与有丝分裂区别开来。减数分裂细胞分裂导致含有一套染色体的细胞，而有丝分裂细胞分裂导致遗传学上相同的含有两套染色体的细胞。减数分裂早期，在“减数分裂”过程中，姐妹染色单体在一些区域配对和经历相互重组。在这一过程中，这些细胞易受DNA链断裂的影响。在减数分裂过程中，细胞对DNA链断裂的反应可能与非生殖细胞对IR诱导的DNA损伤的反应相似。这种解释进一步被研究证实，这些研究证明MEC1在芽胞形成过程中上调10到20倍，表明MCCS1除了在DNA修复中的作用外，在减数分裂过程中也起重要的作用。
实施例9为了识别在发育小鼠睾丸中表达MCCS1的细胞，进行了减数分裂细胞种群中MCCS1表达的Westem印迹分析。如上面实施例8所描述的检查了纯化的粗线期精母细胞，圆精子细胞，浓缩精子细胞，印迹副睾精子细胞的提取物。
粗线期精母细胞，圆和浓缩精子细胞通过用胶原酶和胰蛋白酶-DNase1顺序解离从成熟小鼠脱荚膜的睾丸制备。细胞通过在含2％-4％BSA梯度的滋养林格碳酸氢盐培养基(EKPB)中以单位重力沉降速度分离成分离的种群。粗线期精母细胞和圆精子细胞种群每种至少80％纯度，而浓缩精子细胞约40-50％纯度(主要污染有去核的残余体和一些圆精子细胞)。精子从尾副睾获得。精原细胞的纯化种群直接溶解于含40mM DTT的SDS样品缓冲液中，加热到100℃5分钟，在每个样品中蛋白的数量由酰胺黑方法测定。
在粗线期精母细胞发现了高水平的MCCS1蛋白，在圆精子细胞中该水平显著下降。MCCS1蛋白水平在浓缩精子细胞种群中低得几乎不能测定，这可能反映了制备过程中圆精子细胞的存在(见上面)。副睾精子中没有检测到MCCS1蛋白。所以Western分析确证了免疫细胞活性数据，并提出了MCC所在减数分裂细胞中的作用。
实施例10MCCS1的底物和与MCCS1相互作用的蛋白(例如，细胞循环关卡途径的成员和使MCCS1集中于细胞中的蛋白)可以通过各种试验鉴定。A.底物鉴定MCCS1的底物可以通过在试验中掺入试验化合物来鉴定对激酶活性。MCCS1激酶重悬于20μl激酶缓冲液(25mM Hepes pH7.4，25mMKcl，10mM MgCl2，1mM DTT，2％甘油，0.1％NP40，0.5mM ATP，10uCiγ32P-ATP)并在4μg试验化合物(如，酪蛋白，组蛋白H1，或适当的底物肽)存在或不存在下温育30分钟。反应在12％PAGE凝胶上分离并放射自显影前于Whatman纸上干燥。被激酶转移到试验化合物的磷酸摩尔数用放射自显影或闪烁计数测量。磷酸的转移表明试验化合物是激酶的底物。
蛋白PHAS-1以被鉴定为体外ATP的底物(实施例4)。PHAS-1是一个热和酸稳定的蛋白，它在体内响应胰岛素和生长因子的几个部位磷酸化。PHAS-1结合到mRNA戴帽结合因子，EIF-4E，并阻止戴帽的mRNAs的翻译。PHAS-1在特定丝氨酸残基的磷酸化导致PHAS-1从EIF-4E的分离，因而释放戴帽mRNA翻译的抑制作用。该机理允许蛋白响应特定刺激的快速合成。PHAS-1可以被几种蛋白激酶包括对雷帕霉素敏感的蛋白激酶在体内磷酸化。由于雷帕霉素敏感的蛋白激酶，FRAP，与ATR有关，在FRAP和ATR之间底物特异性上可能有重叠和PHAS-1在体内是这两种蛋白激酶的底物的假设是合理的。为了检验这一假设，从小鼠睾丸细胞提取物免疫沉淀的ATR或由杆状病毒感染的SF9细胞(实施例4)纯化的His-标记ATR，在含10μgPHAS-1的激酶缓冲液(25mM Hepes pH7.4，25mM KCl，10mM MgCl2，1mM DTT，0.1％NP40，10μM ATP和10uCiγ32P-ATP)中于37℃温育20分钟。因为已知磷酸化的PHAS-1结合于磷酸纤维素纸上，该反应点滴到磷酸纤维素离心柱上，在2500×g离心，用0.5ml 75mM磷酸洗两次，用0.5ml无水乙醇洗一次。然后把磷酸纤维素圆盘这一到闪烁计数管中，记录每分钟掺入到PHAS-1蛋白的数目。ATR容易地磷酸化PHAS-1，而阴性对照显示较少或无PHAS-1磷酸化。为了定位那个残基被磷酸化，合成了下列含有丝氨酸和苏氨酸残基代表PHAS-1序列的肽。
肽PH-1MSGGSSCQTPSRAIPATRR(SEQ ID NO36)肽PH-2GDYSTTPGGTLFSTTPGGTRR(SEQ ID NO37)肽PH-3ECRNSPVTKTRR(SEQ ID NO38)肽PH-4GVTSPSSDEPRR(SEQ ID NO39)
肽PH-5MEASQSHLRR(SEQ ID NO40)肽PH-6RRNSPEDKRAGG(SEQ ID NO41)肽PH-7GEESQFEMDIRR(SEQ ID NO42)在相同激酶反应中检测的这些肽以测定那个肽被ATR磷酸化。该肽然后在如实施例11所述的试验中被用作ATR或MCCS1底物以鉴别调制剂。
相同的激酶反应也被用于测定已知是其它蛋白激酶底物的如组氨酸H1(Upstate biotechnology，Inc.，Waltham，NY)和髓鞘碱性蛋白(GibcoBRL，Gaithersburg，MD)那样的蛋白是否是MCCS1和ATR的底物。在试验条件下没有观察到组氨酸H1或髓鞘碱性蛋白的磷酸化。而且，来自p53已知是DNA-PK底物的肽在试验中也没有被磷酸化。。B.相互作用蛋白的鉴别相互作用蛋白可以通过下列试验鉴别。
本发明考虑的首次试验是双杂交筛选。双杂交系统是由酵母发展的[Chien等，proc.Natl.Acad.Sci.USA，889578-9582(1991)]，它基于活化报道基因的转录因子的体内功能重建。特别地，编码与MCCS1相互作用蛋白的多肽如下分离在通过具有DNA结合区域和一个活化区域的转录因子调节的启动子控制下，转化或转染用包含报道基因的DNA结构的适当宿主细胞；在宿主细胞表达第一杂交DNA序列，该序列编码部分或全部MCCS1和DNA结合区域或转录因子的活化区域的首次融合；在宿主细胞中表达第二杂交DNA序列库，该序列编码部分或全部推定MCCS1结合蛋白以及DNA结合区域或不掺入首次融合转录因子的活化区域；在特定宿主细胞通过测定宿主细胞中报道基因产物的生成来测定MCCS1结合蛋白与MCCS1的结合；并从该特定宿主细胞分离编码相互作用蛋白的第二杂交DNA序列。目前在试验中优选使用的是驱动报道基因表达的lexA，lacZ报道基因，包含lexA DNA结合区域和GAL4反式激活区域的转录因子，以及酵母宿主细胞。
鉴别与MCCS1相互作用蛋白的其它试验包括固定化MCCS1或一种试验蛋白，可测定地标记非固定化结合部分，一同温育结合部分并测定标记结合体的数量。结合标记物表明试验蛋白与MCCS1的相互作用。
鉴别MCCS1相互作用蛋白试验的其它类型包括在覆盖(或浸渍)荧光剂的固体载体上固定化MCCS1或其片断，用能够激发荧光剂的化合物标记试验蛋白质，使固定化的MCCS1与标记的试验蛋白接触，检测荧光剂的光发射，并鉴定做为试验蛋白的相互作用蛋白，它导致由荧光剂形成的光发射。另外，在试验中可固定化推断的相互作用蛋白并标记MCCS1。
实施例11MCCS1的调制剂包含MCCS1变体和其它的分子。调制剂会影响MCCS1激酶活性，其在细胞中的位置，和/或其与细胞循环关卡途径成员的相互作用。目前优选的做为突变或开发选择性调制剂的靶点的MCCS1区域包括下列四个部分MCCS1α氨基末端效应子区域(SEQID NO31的氨基酸1到1081)，MCCS1β氨基末端效应子的区域(SEQID NO33的氨基酸1到1150)，MCCS1αrad3+区域(SEQ ID NO31的氨基酸1082到2082)，MCCS1βrad3+区域(SEQ ID NO33的氨基酸1151到2151)，MCCS1αPIK区域(SEQ ID NO31的氨基酸2083到2410)，以及MCCS1βPIK区域(SEQ ID NO33的氨基酸2152到2480)。
具有在激酶区域突变的MCCS1变体做为放射敏感剂可能是有用的。由本发明特别预期的突变是在氨基酸2241位的MCCS1α天冬氨酸，在2246位的天冬酰胺，和在SEQ ID NO31的2260位的MCCS1α天冬氨酸用丙氨酸或蛋氨酸取代，以及在MCCS1β的相应突变。在rad3+基因的类似突变导致酵母对放射超敏。另外，发现在带有AT的病人中ATM的激酶区域突变，AT是一种造成放射敏感性的疾病。
此外，组合库，肽和肽模仿物，限定的化学实体，寡核苷酸，以及天然产物库可以在如下所述的那些试验中筛选做为调制剂的活性。
例如，用于鉴别MCCS1激酶活性调制剂的试验涉及在含γ-32P-ATP和存在或不存在试验化合物的外源激酶底物的激酶缓冲液中温育MCCS1激酶样品，并测定转移到底物的磷酸摩尔数。例如，2μg 50mM咪唑洗脱液加入到激酶缓冲液中。(见实施例6)。反应在37℃温育20分钟，在放射自显影或Western分析前SDS-PAGE分析样品。与不存在试验底物下磷酸转移到底物的摩尔数相比存在试验底物下磷酸转移到底物的摩尔数增加说明该试验化合物是所说的MCCS1激酶的活化剂。相反，与不存在试验化合物下磷酸转移到底物的摩尔数相比存在试验化合物下磷酸转移到底物的摩尔数减少说明该试验化合物是所说的MCCS1激酶的抑制剂。
而且，鉴别调节MCCS1与其它蛋白的相互作用的化合物的试验可包括在通过具有DNA结合区域和一个活化区域的转录因子调节的启动子控制下转化或转染带有含报道基因的DNA结构的适当宿主细胞；在宿主细胞表达第一杂交DNA序列，该序列表达部分或全部MCCS1和DNA结合区域或转录因子的活化区域的首次融合；在宿主细胞中表达第二杂交DNA序列，该序列编码部分或全部与MCCS1相互作用蛋白和DNA结合区域或不掺入首次融合转录因子的活化区域；通过在特定宿主细胞由测定报道基因产物在试验化合物存在和不存在下在宿主细胞的产生来检测相互作用蛋白对MCCS1的结合，评价试验化合物在MCCS1和相互作用蛋白相互作用的影响；鉴别调节化合物为那些与不存在调节化合物时报道基因产物的产生相比报道基因产物的改变产生的化合物。目前在试验中优选使用的是推动报道基因表达的lexA启动子，lacZ报道基因，包含lexA DNA结合蛋白区域和GAL4反式激活区域的转录因子，以及酵母宿主细胞。
鉴别调节MCCS1与一种相互作用蛋白相互作用的其它试验包括固定化MCCS1或天然MCCS1相互作用蛋白，可测定地标记非固定化结合部分，一同温育结合部分并测定试验化合物在标记结合物数量上的影响，其中与试验化合物不存在时标记化合物的数量相比试验化合物存在时标记结合物的减少，说明试验剂是MCCS1与蛋白相互作用的抑制剂。相反，与试验化合物不存在时标记化合物的数量相比试验化合物存在时标记结合物的增加，说明推定的调制剂是MCCS1与蛋白相互作用的活化剂。而由本发明考虑的鉴别调节MCCS1和一种相互作用蛋白之间结合的化合物的其它方法包括在涂有(或浸渍)荧光试剂的固体载体上固定化MCCS1或其片断，用能够激发荧光试剂的化合物标记相互作用蛋白，在试验化合物存在或不存在下用标记相互作用蛋白接触固定化的MCCS1，检测荧光剂的光发射，并鉴别做为那些与不存在试验化合物下荧光剂的光发射相比影响荧光剂光发射的试验化合物的调节化合物。或者，在试验中可以固定化MCCS1相互作用蛋白和标记MCCS1。
实施例12用于鉴别MCCS1或ATM调制剂的基于相比的互补实验描述如下。
在一种类型的试验中，宿主细胞(例如esr-1酵母细胞)用如实施例4所述的编码MCCS1 DNA转化。esr 1-1酵母菌株对用紫外(UV)光处理正常地敏感，但表达MCCS1或ATR的esr 1-1酵母细胞对用UV处理不再敏感。转化的酵母细胞中加入试验化合物，并测定试验化合物对转化的宿主细胞UV敏感性的影响。MCCS1或ATR活性抑制剂的试验化合物恢复对转化的esr 1-1细胞的UV敏感性。或者，esr 1-1tel1双突变酵母细胞代替esr 1-1酵母细胞被用作宿主细胞。TEL1基因是与ATM同源的，TEL1突变在Morrow等，Cell，82831-840(1995)中有描述。本发明也特别地考虑到esr 1-1或esr 1-1tel1双突变体酵母宿主细胞可以用编码ATM的DNA(SEQ ID NO34)转化。
在另外的实施方案中，试验包括断裂剂或代替用UV光处理(如，IR，羟基脲，或DNA损伤剂)的过程。用于该实施方案的适当的宿主细胞可以是那些对其它断裂剂或过程敏感的。
互补试验的其它类型包含哺乳动物宿主细胞，如来自AT病人细胞的细胞株。如上对酵母宿主细胞所述，哺乳动物细胞用编码MCCS1ATR，或ATM的DNA转化，然后加入试验化合物。是MCCS1，ATR或ATM活性抑制剂的试验化合物会恢复未转化的宿主细胞的表型(如，对IR的敏感性)。
以上试验能被用于鉴别抑制MCCS1，ATR和ATM活性的化合物或仅抑制其中一种酶活性的化合物。
在试验的另外类型中，酵母或哺乳宿主细胞被用编码包括MCCS1和ATM区域的各种组合的嵌合多肽转化。MCCS1和ATM显示结构的相反性，并且包含MCCS1和ATM的部分的嵌合多肽在解释MCCS1和ATM两者活性位点和结合区域中是有用的。编码嵌合体的多肽可以通过对技术人员已知的标准分子生物学技术制备并在此做为示范。该嵌合多肽在宿主细胞中被表达，该嵌合体的调制剂可由此处公开的试验鉴别。
实施例13MCCS1和ATM都包含在减数分裂I关卡中。由于这里证明了MCCS1有激酶活性，进行试验以确定是否ATM拥有激酶活性。为了确定ATM的激酶活性，ATM被从MRC-5成纤维细胞(ATCC #171-CCL)中用多克隆抗血清6076免疫沉淀。MRC-5细胞是人肺胚胎二倍体成纤维细胞。MRC-5细胞从第19代ATCC获得并保持在补充以10％胎牛血清，100单位/ml青霉素，100mg/ml链霉素，和100mM非必需氨基酸的极限必需培养基中。培养基和培养基补充物由Gibco LifeTechnologies获得。细胞株保存在37℃含5％C的水饱和温育箱内。
MRC-5细胞提取物通过在冰上用0.5ml裂解缓冲液I(50mMNaPO4，pH7.2；0.5％TritonX-100；2mM EDTA；2nM EGTA；25mMNaF；25mM 2-甘油磷酸；1mM苯甲基氟磺酸[PMSF]；1μg/ml亮抑酶肽；1μg/ml胃酶抑制剂A；2mM DTT)裂解10cm平皿的对数期细胞制备。用橡胶刮铲从平皿上刮下细胞并在杯角超声器(Sonifier250，BransonUltrasonics Corp.，Danburg，CT)中于100输出功率超声90秒，裂解液然后在一个4℃microfuge澄清2分钟。通过加入10μg纯化的兔IgG(Zymad)和30μl蛋白A琼脂糖糊(Pierce)，随后摇动下在4℃温育60分钟进行预清除。向预清除裂解物中加入10μg亲和纯化的6076抗血清(或10μg用0.04mg P45肽预封闭30分钟的6076)，在冰上温育60分钟。通过加入30μl蛋白A琼脂糖糊并摇动下在4℃温育30分钟，随后在裂解缓冲液I中洗四次收集免疫沉淀。
通过用激酶缓冲液(25μM Hepes pH7.7；50mM NaCl；10mM MgCl2；0.1％NP-40；2％甘油；1mMDTT)洗一次，随后在25μl含10μmATP+10μCiγ32P-ATP[50 Ci/mmol]的激酶缓冲液中37℃温育20分钟，进行激酶反应。在用6％聚丙烯酰胺凝胶分离前用加入20μl2×SDS样品缓冲液并煮5分钟停止反应。凝胶干燥并在-80℃加入到X-射线胶片(Kodak，XAR-5)上过夜。
对数期MRC-5细胞的10cm平皿用PBS洗一次，然后在含2％透析过的胎牛血清的Dulbeco改进的Eagle培养基(无甲硫氨酸)中温育30分钟。加入200μCi35S-甲硫氨酸(1000Ci/mmol TRAN35S-LABEL，1CNRadiochemicals)标记细胞2小时。标记的细胞然后用PBS洗一次并在免疫沉淀前于-80℃冷冻。
免疫沉淀复合物在激酶缓冲液中的温育产生一个具有分子量约350,000与ATM在聚丙烯酰胺凝胶上共迁移的磷酸化产物。
用实施例5的抗-AgDH-2(MCCS1)多克隆抗血清免疫沉淀的ATR免疫复合物获得了相似的结果。因而ATR和ATM看来能够自身磷酸化或与蛋白激酶有关系。
为了测定ATR和ATM在减数分裂中的作用，在小鼠精母细胞的表面涂片上利用免疫染色技术来固定化ATR和ATM到睾丸染色体上。识别ATR和ATM的抗体利用抗Cor1小鼠抗体。Cor1是突触染色体的一个轴向/倾向元素的成分[Dobson等，J.Cell Sci.，1072749-2760(1994)]当轴向元素开始在突触出现前，在减数分裂细线期中的每个同系物的姐妹染色单体之间形成时出现Cor1染色体染色。做为同源二倍体突触，在它们之间形成了来自两个同系匹配的轴向元素和中心元素，完成称为联会复合体(SC)的结构。
当Cor1的短延伸开始在突触的任何迹象前出现时，ATR和ATM都不能测定。当同系物开始突触时，两种蛋白在配对叉都可见到；然而，两种蛋白的位置和行为显著地不同。在正常的合线期细胞核，同系物突触阶段，ATR以小量短暂地在沿突触的(未配对)轴不连续的集落出现。做为同系物突触，ATR从这些位置消失。然而，在常染色体二价体的近侧末端附近常见的突触延伸区域，沿突触轴存在ATR集落的聚集。在两个轴元素的相似位置检测到ATR。在全部常染色体不能发现其同源配对体的细胞核中，ATR集落沿这些突触的轴的全长被检测到。雄性，此处X染色体无同系物，ATR集落位于沿未配对的轴。
ATM也可显现为集落，并在合线期阶段首次做为同系物突触被检测到，但是ATM定位比ATR困难。当同源常染色体的轴向元素接触时，沿突触的轴首次发现ATM。然而，粗线期中期阶段，常染色体突触已完成后，ATM集落出现在X染色体轴上。ATM定位持续保留在完全突触的二价体进入粗线期，一种在小鼠卵母细胞中持续3天，在小鼠酵母细胞中持续6天的亚阶段。在粗线期期间，集落的数目逐渐下降，在最终消失在中到晚粗线期之前短暂地稳定在粗线期中期。所以，ATR和ATM蛋白姐妹在减数分裂I的特有阶段起重要和互补的作用。
ATR的参与看来在减数分裂前期的早期是短暂的，而ATM的作用似乎更长。然而，ATR和ATM两者通过完成相似的关卡功能协调减数分裂前期的各种事件。
前述的用作说明的实施例涉及目前发明的优选实施方案，期待本领域技术人员想到的其许多的修改和变动。所以仅有如出现在附加权利要求那样的限制应放在本发明的范围内。
序列列表(1)总说明(i)申请人ICOS公司(ii)发明题目细胞周期关卡与PIK相关的激酶材料和方法(iii)序列数目42(iv)通讯地址(A)收信人Marshall，O’Toole，Gerstein，Murray&borun(B)街道6300 Sears Tower，233 S.Wacker Dr.
(C)城市芝加哥(D)州依利诺(E)国家美国(F)邮政编码60606(v)计算机可读方式(A)介质类型磁盘(B)计算机IBM PC兼容机(C)操作系统PC-DOS/MS-DOS(D)软件PatentIn Release#1.0，#1.30版(vi)当前申请数据(A)申请号(B)归档号(C)分类(viii)代理人资料(A)姓名Noland，Greta E.
(B)注册号35,302(C)参考/摘要号27866/33607(ix)电信资料(A)电话(312)474-6300(B)电传(312)474-0488(C)用户电报25-3856(2)SEQ ID NO1的说明(i)序列特征(A)长度7621个碱基对(B)类型核苷酸(C)链型单链(D)拓扑结构线性(ii)分子类型cDNA(vii)直接来源(B)克隆pBSHFB2HT2-27(ix)特征(A)姓名/符号CDS(B)位置333..7559(xi)序列描述SEQ ID NO1CTTGTGAAGA GAATGTTTTA CACTCTIGTT AGTGAAGTTT ATTCTTTAAA AGTCAATCGT 60CAAGGATTTA GCAAATGAAT TAGCACTTCG GATATACTTG TTTATTTAAT ATCTTTTTTG 120TTTATTTCAA AGAATTCAGT AATTGGATCA TAACGAGACT TCTGCGGATT GCAGCAACTC 180CCTCCTGTCA TTTGTTACAC AAGAAAATCT GTGAAGTCAT CTGTTCATTA TTATTTCTTT 240TTAAAAGCAA GAGTCCTGCT ATTTTTGGGG TACTCACAAA AGAATTATTA CAACTTTTTG 300AAGACTTGGT TTACCTCCAT AGAAGAAATG TG ATG GGT CAT GCT GTG GAA TGG 353Met Gly His Ala Val Glu Trp1 5CCA GTG GTC ATG AGC CGA TTT TTA AGT CAA TTA GAT GAA CAC ATG GGA 401Pro Val Val Met Ser Arg Phe Leu Ser Gln Leu Asp Glu His Met Gly10 15 20TAT TTA CAA TCA GCT CCT TTG CAG TTG ATG AGT ATG CAA AAA TTA GAA 449Tyr Leu Gln Ser Ala Pro Leu Gln Leu Met Ser Met Gln Lys Leu Glu25 30 35TTT ATT GAA GTC ACT TTA TTA ACG GTT CTT ACT CGT ATT ATT GCA ATT 497Phe Ile Glu Val Thr Leu Leu Thr Val Leu Thr Arg Ile Ile Ala Ile40 45 50 55GTG TTT TTT AGA AGG CAA GAA CTC TTA CTT TGG CAG ATA GGT TGT GTT 545Val Phe Phe Arg Arg Gln Glu Leu Leu Leu Trp Gln Ile Gly Cys Val60 65 70CTG CTA GAG TAT GGT AGT CCA AAA ATT AAA TCC CTA GCA ATT AGC TTT 593Leu Leu Glu Tyr Gly Ser Pro Lys Ile Lys Ser Leu Ala Ile Ser Phe75 80 85TTA ACA GAA CTT TTT CAG CTT GGA GGA CTA CCA GCA CAA CCA GCT AGC 641Leu Thr Glu Leu Phe Gln Leu Gly Gly Leu Pro Ala Gln Pro Ala Ser90 95 100ACT TTT TTC AGC TCA TTT TTG GAA TTA TTA AAA CAC CTT GTA GAA ATG 689Thr Phe Phe Ser Ser Phe Leu Glu Leu Leu Lys His Leu Val Glu Met105 110 115GAT ACT GAC CAA TTG AAA CTC TAT GAA GAG CCA TTA TCA AAG CTG ATA 737Asp Thr Asp Gln Leu Lys Leu Tyr Glu Glu Pro Leu Ser Lys Leu Ile120 125 130 135AAG ACA CTA TTT CCC TTT GAA GCA GAA GCT TAT AGA AAT ATT GAA CCT 785Lys Thr Leu Phe Pro Phe Glu Ala Glu Ala Tyr Arg Asn Ile Glu Pro140 145 150GTC TAT TTA AAT ATG CTG CTG GAA AAA CTC TGT GTC ATG TTT GAA GAC 833Val Tyr Leu Asn Met Leu Leu Glu Lys Leu Cys Val Met Phe Glu Asp155 160 165GGT GTG CTC ATG CGG CTT AAG TCT GAT TTG CTA AAA GCA GCT TTG TGC 881Gly Val Leu Met Arg Leu Lys Ser Asp Leu Leu Lys Ala Ala Leu Cys170 175 180CAT TTA CTG CAG TAT TTC CTT AAA TTT GTG CCA GCT GGG TAT GAA TCT 929His Leu Leu Gln Tyr Phe Leu Lys Phe Val Pro Ala Gly Tyr Glu Ser185 190 195GCT TTA CAA GTC AGG AAG GTC TAT GTG AGA AAT ATT TGT AAA GCT CTT 977Ala Leu Gln Val Arg Lys Val Tyr Val Arg Asn Ile Cys Lys Ala Leu200 205 210 215TTG GAT GTG CTT GGA ATT GAG GTA GAT GCA GAG TAC TTG TTG GGC CCA 1025Leu Asp Val Leu Gly Ile Glu Val Asp Ala Glu Tyr Leu Leu Gly Pro220 225 230CTT TAT GCA GCT TTG AAA ATG GAA AGT ATG GAA ATC ATT GAG GAG ATT 1073Leu Tyr Ala Ala Leu Lys Met Glu Ser Met Glu Ile Ile Glu Glu Ile235 240 245CAA TGC CAA ACT CAA CAG GAA AAC CTC AGC AGT AAT AGT GAT GGA ATA 1121Gln Cys Gln Thr Gln Gln Glu Asn Leu Ser Ser Asn Ser Asp Gly Ile250 255 260TCA CCC AAA AGG CGT CGT CTC AGC TCG TCT CTA AAC CCT TCT AAA AGA 1169Ser Pro Lys Arg Arg Arg Leu Ser Ser Ser Leu Asn Pro Ser Lys Arg265 270 275GCA CCA AAA CAG ACT GAG GAA ATT AAA CAT GTG GAC ATG AAC CAA AAG 1217Ala Pro Lys Gln Thr Glu Glu Ile Lys His Val Asp Met Asn Gln Lys280 285 290 295AGC ATA TTA TGG AGT GCA CTG AAA CAG AAA GCT GAA TCC CTT CAG ATT 1265Ser Ile Leu Trp Ser Ala Leu Lys Gln Lys Ala Glu Ser Leu Gln Ile300 305 310TCC CTT GAA TAC AGT GGC CTA AAG AAT CCT GTT ATT GAG ATG TTA GAA 1313Ser Leu Glu Tyr Ser Gly Leu Lys Asn Pro Val Ile Glu Met Leu Glu315 320 325GGA ATT GCT GTT GTC TTA CAA CTG ACT GCT CTG TGT ACT GTT CAT TGT 1361Gly Ile Ala Val Val Leu Gln Leu Thr Ala Leu Cys Thr Val His Cys330 335 340TCT CAT CAA AAC ATG AAC TGC CGT ACT TTC AAG GAC TGT CAA CAT AAA 1409Ser His Gln Asn Met Asn Cys Arg Thr Phe Lys Asp Cys Gln His Lys345 350 355TCC AAG AAG AAA CCT TCT GTA GTG ATA ACT TGG ATG TCA TTG GAT TTT 1457Ser Lys Lys Lys Pro Ser Val Val Ile Thr Trp Met Ser Leu Asp Phe360 365 370 375TAC ACA ACA GTG CTT AAG AGC TGT AGA AGG TTG TTA GAA TCT GTT CAG 1505Tyr Thr Thr Val Leu Lys Ser Cys Arg Arg Leu Leu Glu Ser Val Gln380 385 390AAA CGG ACT GGA GGC AAC ATT GAT AAG GTG GTG AAA ATT TAT GAT GCT 1553Lys Arg Thr Gly Gly Asn Ile Asp Lys Val Val Lys Ile Tyr Asp Ala395 400 405TTG ATT TAT ATG CAA GTA AAC AGT TCA TTT GAA GAT CAT ATC CTG GAA 1601Leu Ile Tyr Met Gln Val Asn Ser Ser Phe Glu Asp His Ile Leu Glu410 415 420GAT TTA TGT GGA ATG CTC TCA CTT CCA TGG ATT TAT TCC CAT TCT GAT 1649Asp Leu Cys Gly Met Leu Ser Leu Pro Trp Ile Tyr Ser His Ser Asp425 430 435GAT GGC TGT TTA AAG TTG ACC ACA TTT GCC GCT AAT CTT CTA ACA TTA 1697Asp Gly Cys Leu Lys Leu Thr Thr Phe Ala Ala Asn Leu Leu Thr Leu440 445 450 455AGC TGT AGG ATT TCA GAT AGC TAT TCA CCA CAG GCA CAA TCA CGA TGT 1745Ser Cys Arg Ile Ser Asp Ser Tyr Ser Pro Gln Ala Gln Ser Arg Cys460 465 470GTG TTT CTT CTG ACT CTG TTT CCA AGA AGA ATA TTC CTT GAG TGG AGA 1793Val Phe Leu Leu Thr Leu Phe Pro Arg Arg Ile Phe Leu Glu Trp Arg475 480 485ACA GCA GTT TAC AAC TGG GCC CTG CAG AGC TCC CAT GAA GTA ATC CGG 1841Thr Ala Val Tyr Asn Trp Ala Leu Gln Ser Ser His Glu Val Ile Arg490 495 500GCT AGT TGT GTT AGT GGA TTT TTT ATC TTA TTG CAG CAG CAG AAT TCT 1889Ala Ser Cys Val Ser Gly Phe Phe Ile Leu Leu Gln Gln Gln Asn Ser505 510 515TGT AAC AGA GTT CCC AAG ATT CTT ATA GAT AAA GTC AAA GAT GAT TCT 1937Cys Asn Arg Val Pro Lys Ile Leu Ile Asp Lys Val Lys Asp Asp Ser520 525 530 535GAC ATT GTC AAG AAA GAA TTT GCT TCT ATA CTT GGT CAA CTT GTC TGT 1985Asp Ile Val Lys Lys Glu Phe Ala Ser Ile Leu Gly Gln Leu Val Cys540 545 550ACT CTT CAC GGC ATG TTT TAT CTG ACA AGT TCT TTA ACA GAA CCT TTC 2033Thr Leu His Gly Met Phe Tyr Leu Thr Ser Ser Leu Thr Glu Pro Phe555 560 565TCT GAA CAC GGA CAT GTG GAC CTC TTC TGT AGG AAC TTG AAA GCC ACT 2081Ser Glu His Gly His Val Asp Leu Phe Cys Arg Asn Leu Lys Ala Thr570 575 580TCT CAA CAT GAA TGT TCA TCT TCT CAA CTA AAA GCT TCT GTC TGC AAG 2129Ser Gln His Glu Cys Ser Ser Ser Gln Leu Lys Ala Ser Val Cys Lys585 590 595CCA TTC CTT TTC CTA CTG AAA AAA AAA ATA CCT AGT CCA GTA AAA CTT 2177Pro Phe Leu Phe Leu Leu Lys Lys Lys Ile Pro Ser Pro Val Lys Leu600 605 610 615GCT TTC ATA GAT AAT CTA CAT CAT CTT TGT AAG CAT CTT GAT TTT AGA 2225Ala Phe Ile Asp Asn Leu His His Leu Cys Lys His Leu Asp Phe Arg620 625 630GAA GAT GAA ACA GAT GTA AAA GCA GTT CTT GGA ACT TTA TTA AAT TTA 2273Glu Asp Glu Thr Asp Val Lys Ala Val Leu Gly Thr Leu Leu Asn Leu635 640 645ATG GAA GAT CCA GAC AAA GAT GTT AGA GTG GCT TTT AGT GGA AAT ATC 2321Met Glu Asp Pro Asp Lys Asp Val Arg Val Ala Phe Ser Gly Asn Ile650 655 660AAG CAC ATA TTG GAA TCC TTG GAC TCT GAA GAT GGA TTT ATA AAG GAG 2369Lys His Ile Leu Glu Ser Leu Asp Ser Glu Asp Gly Phe Ile Lys Glu665 670 675CTT TTT GTC TTA AGA ATG AAG GAA GCA TAT ACA CAT GCC CAA ATA TCA 2417Leu Phe Val Leu Arg Met Lys Glu Ala Tyr Thr His Ala Gln Ile Ser680 685 690 695AGA AAT AAT GAG CTG AAG GAT ACC TTG ATT CTT ACA ACA GGG GAT ATT 2465Arg Asn Asn Glu Leu Lys Asp Thr Leu Ile Leu Thr Thr Gly Asp Ile700 705 710GGA AGG GCC GCA AAA GGA GAT TTG GTA CCA TTT GCA CTC TTA CAC TTA 2513Gly Arg Ala Ala Lys Gly Asp Leu Val Pro Phe Ala Leu Leu His Leu715 720 725TTG CAT TGT TTG TTA TCC AAG TCA GCA TCT GTC TCT GGA GCA GCA TAC 2561Leu His Cys Leu Leu Ser Lys Ser Ala Ser Val Ser Gly Ala Ala Tyr730 735 740ACA GAA ATT AGA GCT CTG GTT GCA GCT AAA AGT GTT AAA CTG CAA AGT 2609Thr Glu Ile Arg Ala Leu Val Ala Ala Lys Ser Val Lys Leu Gln Ser745 750 755TTT TTC AGC CAG TAT AAG AAA CCC ATC TGT CAG TTT TTG GTA GAA TCC 2657Phe Phe Ser Gln Tyr Lys Lys Pro Ile Cys Gln Phe Leu Val Glu Ser760 765 770 775CTT CAC TCT AGT CAG ATG ACA GCA CTT CCG AAT ACT CCA TGC CAG AAT 2705Leu His Ser Ser Gln Met Thr Ala Leu Pro Asn Thr Pro Cys Gln Asn780 785 790GCT GAC GTG CGA AAA CAA GAT GTG GCT CAC CAG AGA GAA ATG GCT TTA 2753Ala Asp Val Arg Lys Gln Asp Val Ala His Gln Arg Glu Met Ala Leu795 800 805AAT ACG TTG TCT GAA ATT GCC AAC GTT TTC GAC TTT CCT GAT CTT AAT 2801Asn Thr Leu Ser Glu Ile Ala Asn Val Phe Asp Phe Pro Asp Leu Asn810 815 820CGT TTT CTT ACT AGG ACA TTA CAA GTT CTA CTA CCT GAT CTT GCT GCC 2849Arg Phe Leu Thr Arg Thr Leu Gln Val Leu Leu Pro Asp Leu Ala Ala825 830 835AAA GCA AGC CCT GCA GCT TCT GCT CTC ATT CGA ACT TTA GGA AAA CAA 2897Lys Ala Ser Pro Ala Ala Ser Ala Leu Ile Arg Thr Leu Gly Lys Gln840 845 850 855TTA AAT GTC AAT CGT AGA GAG ATT TTA ATA AAC AAC TTC AAA TAT ATT 2945Leu Asn Val Asn Arg Arg Glu Ile Leu Ile Asn Asn Phe Lys Tyr Ile860 865 870TTT TCT CAT TTG GTC TGT TCT TGT TCC AAA GAT GAA TTA GAA CGT GCC 2993Phe Ser His Leu Val Cys Ser Cys Ser Lys Asp Glu Leu Glu Arg Ala875 880 885CTT CAT TAT CTG AAG AAT GAA ACA GAA ATT GAA CTG GGG AGC CTG TTG 3041Leu His Tyr Leu Lys Asn Glu Thr Glu Ile Glu Leu Gly Ser Leu Leu890 895 900AGA CAA GAT TTC CAA GGA TTG CAT AAT GAA TTA TTG CTG CGT ATT GGA 3089Arg Gln Asp Phe Gln Gly Leu His Asn Glu Leu Leu Leu Arg Ile Gly905 910 915GAA CAC TAT CAA CAG GTT TTT AAT GGT TTG TCA ATA CTT GCC TCA TTT 3137Glu His Tyr Gln Gln Val Phe Asn Gly Leu Ser Ile Leu Ala Ser Phe920 925 930 935GCA TCC AGT GAT GAT CCA TAT CAG GGC CCG AGA GAT ATC ATA TCA CCT 3185Ala Ser Ser Asp Asp Pro Tyr Gln Gly Pro Arg Asp Ile Ile Ser Pro940 945 950GAA CTG ATG GCT GAT TAT TTA CAA CCC AAA TTG TTG GGC ATT TTG GCT 3233Glu Leu Met Ala Asp Tyr Leu Gln Pro Lys Leu Leu Gly Ile Leu Ala955 960 965TTT TTT AAC ATG CAG TTA CTG AGC TCT AGT GTT GGC ATT GAA GAT AAG 3281Phe Phe Asn Met Gln Leu Leu Ser Ser Ser Val Gly Ile Glu Asp Lys970 975 980AAA ATG GCC TTG AAC AGT TTG ATG TCT TTG ATG AAG TTA ATG GGA CCC 3329Lys Met Ala Leu Asn Ser Leu Met Ser Leu Met Lys Leu Met Gly Pro985 990 995AAA CAT GTC AGT TCT GTG AGG GTG AAG ATG ATG ACC ACA CTG AGA ACT 3377Lys His Val Ser Ser Val Arg Val Lys Met Met Thr Thr Leu Arg Thr1000100510101015GGC CTT CGA TTC AAG GAT GAT TTT CCT GAA TTG TGT TGC AGA GCT TGG 3425Gly Leu Arg Phe Lys Asp Asp Phe Pro Glu Leu Cys Cys Arg Ala Trp102010251030GAC TGC TTT GTT CGC TGC CTG GAT CAT GCT TGT CTG GGC TCC CTT CTC 3473Asp Cys Phe Val Arg Cys Leu Asp His Ala Cys Leu Gly Ser Leu Leu103510401045AGT CAT GTA ATA GTA GCT TTG TTA CCT CTT ATA CAC ATC CAG CCT AAA 3521Ser His Val Ile Val Ala Leu Leu Pro Leu Ile His Ile Gln Pro Lys105010551060GAA ACT GCA GCT ATC TTC CAC TAC CTC ATA ATT GAA AAC AGG GAT GCT 3569Glu Thr Ala Ala Ile Phe His Tyr Leu Ile Ile Glu Asn Arg Asp Ala106510701075GTG CAA GAT TTT CTT CAT GAA ATA TAT TTT TTA CCT GAT CAT CCA GAA 3617Val Gln Asp Phe Leu His Glu Ile Tyr Phe Leu Pro Asp His Pro Glu1080108510901095TTA AAA AAG ATA AAA GCC GTT CTC CAG GAA TAC AGA AAG GAG ACC TCT 3665Leu Lys Lys Ile Lys Ala Val Leu Gln Glu Tyr Arg Lys Glu Thr Ser110011051110GAG AGC ACT GAT CTT CAG ACA ACT CTT CAG CTC TCT ATG AAG GCC ATT 3713Glu Ser Thr Asp Leu Gln Thr Thr Leu Gln Leu Ser Met Lys Ala Ile111511201125CAA CAT GAA AAT GTC GAT GTT CGT ATT CAT GCT CTT ACA AGC TTG AAG 3761Gln His Glu Asn Val Asp Val Arg Ile His Ala Leu Thr Ser Leu Lys113011351140GAA ACC TTG TAT AAA AAT CAG GAA AAA CTG ATA AAG TAT GCA ACA GAC 3809Glu Thr Leu Tyr Lys Asn Gln Glu Lys Leu Ile Lys Tyr Ala Thr Asp114511501155AGT GAA ACA GTA GAA CCT ATT ATC TCA CAG TTG GTG ACA GTG CTT TTG 3857Ser Glu Thr Val Glu Pro Ile Ile Ser Gln Leu Val Thr Val Leu Leu1160116511701175AAA GGT TGC CAA GAT GCA AAC TCT CAA GCT CGG TTG CTC TGT GGG GAA 3905Lys Gly Cys Gln Asp Ala Asn Ser Gln Ala Arg Leu Leu Cys Gly Glu118011851190TGT TTA GGG GAA TTG GGG GCG ATA GAT CCA GGT CGA TTA GAT TTC TCA 3953Cys Leu Gly Glu Leu Gly Ala Ile Asp Pro Gly Arg Leu Asp Phe Ser119512001205ACA ACT GAA ACT CAA GGA AAA GAT TTT ACA TTT GTG ACT GGA GTA GAA 4001Thr Thr Glu Thr Gln Gly Lys Asp Phe Thr Phe Val Thr Gly Val Glu121012151220GAT TCA AGC TTT GCC TAT GGA TTA TTG ATG GAG CTA ACA AGA GCT TAC 4049Asp Ser Ser Phe Ala Tyr Gly Leu Leu Met Glu Leu Thr Arg Ala Tyr122512301235CTT GCG TAT GCT GAT AAT AGC CGA GCT CCA GAT TCA GCT GCC TAT GCC 4097Leu Ala Tyr Ala Asp Asn Ser Arg Ala Pro Asp Ser Ala Ala Tyr Ala1240124512501255ATT CAG GAG TTG CTT TCT ATT TAT GAC TGT AGA GAG ATG GAG ACC AAC 4145Ile Gln Glu Leu Leu Ser Ile Tyr Asp Cys Arg Glu Met Glu Thr Asn126012651270GGC CCA GGT CAC CAA TTG TGG AGG AGA TTT CCT GAG CAT GTT CGG GAA 4193Gly Pro Gly His Gln Leu Trp Arg Arg Phe Pro Glu His Val Arg Glu127512801285ATA CTA GAA CCT CAT CTA AAT ACC AGA TAC AAG AGT TCT CAG AAG TCA 4241Ile Leu Glu Pro His Leu Asn Thr Arg Tyr Lys Ser Ser Gln Lys Ser129012951300ACC GAT TGG TCT GGA GTA AAG AAG CCA ATT TAC TTA AGT AAA TTG GGT 4289Thr Asp Trp Ser Gly Val Lys Lys Pro Ile Tyr Leu Ser Lys Leu Gly130513101315AGT AAC TTT GCA GAA TGG TCA GCA TCT TGG GCA GGT TAT CTT ATT ACA 4337Ser Asn Phe Ala Glu Trp Ser Ala Ser Trp Ala Gly Tyr Leu Ile Thr1320132513301335AAG GTT CGA CAT GAT CTT GCC AGT AAA ATT TTC ACC TGC TGT AGC ATT 4385Lys Val Arg His Asp Leu Ala Ser Lys Ile Phe Thr Cys Cys Ser Ile134013451350ATG ATG AAG CAT GAT TTC AAA GTG ACC ATC TAT CTT CTT CCA CAT ATT 4433Met Met Lys His Asp Phe Lys Val Thr Ile Tyr Leu Leu Pro His Ile135513601365CTG GTG TAT GTC TTA CTG GGT TGT AAT CAA GAA GAT CAG CAG GAG GTT 4481Leu Val Tyr Val Leu Leu Gly Cys Asn Gln Glu Asp Gln Gln Glu Val137013751380TAT GCA GAA ATT ATG GCA GTT CTA AAG CAT GAC GAT CAG CAT ACC ATA 4529Tyr Ala Glu Ile Met Ala Val Leu Lys His Asp Asp Gln His Thr Ile138513901395AAT ACC CAA GAC ATT GCA TCT GAT CTG TGT CAA CTC AGT ACA CAG ACT 4577Asn Thr Gln Asp Ile Ala Ser Asp Leu Cys Gln Leu Ser Thr Gln Thr1400140514101415GTG TTC TCC ATG CTT GAC CAT CTC ACA CAG TGG GCA AGG CAC AAA TTT 4625Val Phe Ser Met Leu Asp His Leu Thr Gln Trp Ala Arg His Lys Phe142014251430CAG GCA CTG AAA GCT GAG AAA TGT CCA CAC AGC AAA TCA AAC AGA AAT 4673Gln Ala Leu Lys Ala Glu Lys Cys Pro His Ser Lys Ser Asn Arg Asn143514401445AAG GTA GAC TCA ATG GTA TCT ACT GTG GAT TAT GAA GAC TAT CAG AGT 4721Lys Val Asp Ser Met Val Ser Thr Val Asp Tyr Glu Asp Tyr Gln Ser145014551460GTA ACC CGT TTT CTA GAC CTC ATA CCC CAG GAT ACT CTG GCA GTA GCT 4769Val Thr Arg Phe Leu Asp Leu Ile Pro Gln Asp Thr Leu Ala Val Ala146514701475TCC TTT CGC TCC AAA GCA TAC ACA CGA GCT GTA ATG CAC TTT GAA TCA 4817Ser Phe Arg Ser Lys Ala Tyr Thr Arg Ala Val Met His Phe Glu Ser1480148514901495TTT ATT ACA GAA AAG AAG CAA AAT ATT CAG GAA CAT CTT GGA TTT TTA 4865Phe Ile Thr Glu Lys Lys Gln Asn Ile Gln Glu His Leu Gly Phe Leu150015051510CAG AAA TTG TAT GCT GCT ATG CAT GAA CCT GAT GGA GTG TCC GGA GTC 4913Gln Lys Leu Tyr Ala Ala Met His Glu Pro Asp Gly Val Ser Gly Val151515201525AGT GCA ATT AGA AAG GCA GAA CCA TCT CTA AAA GAA CAG ATC CTT GAA 4961Ser Ala Ile Arg Lys Ala Glu Pro Ser Leu Lys Glu Gln Ile Leu Glu153015351540CAT GAA AGC CTT GGC TTG CTG AGG GAT GCC ACT GCT TGT TAT GAC AGG 5009His Glu Ser Leu Gly Leu Leu Arg Asp Ala Thr Ala Cys Tyr Asp Arg154515501555GCT ATT CAG CTA GAA CCA GAC CAG ATC ATT CAT TAC CAT GGT GTA GTA 5057Ala Ile Gln Leu Glu Pro Asp Gln Ile Ile His Tyr His Gly Val Val1560156515701575AAG TCC ATG TTA GGT CTT GGT CAG CTG TCT ACT GTT ATC ACT CAG GTG 5105Lys Ser Met Leu Gly Leu Gly Gln Leu Ser Thr Val Ile Thr Gln Val158015851590AAT GGA GTG CAT GCT AAC AGG TCC GAG TGG ACA GAT GAA TTA AAC ACG 5153Asn Gly Val His Ala Asn Arg Ser Glu Trp Thr Asp Glu Leu Asn Thr159516001605TAC AGA GTG GAA GCA GCT TGG AAA TTG TCA CAG TGG GAT TTG GTG GAA 5201Tyr Arg Val Glu Ala Ala Trp Lys Leu Ser Gln Trp Asp Leu Val Glu161016151620AAC TAT TTG GCA GCA GAT GGA AAA TCT ACA ACA TGG AGT GTC AGA CTG 5249Asn Tyr Leu Ala Ala Asp Gly Lys Ser Thr Thr Trp Ser Val Arg Leu162516301635GGA CAG CTA TTA TTA TCA GCC AAA AAA AGA GAT ATC ACA GCT TTT TAT 5297Gly Gln Leu Leu Leu Ser Ala Lys Lys Arg Asp Ile Thr Ala Phe Tyr1640164516501655GAC TCA CTG AAA CTA GTG AGA GCA GAA CAA ATT GTA CCT CTT TCA GCT 5345Asp Ser Leu Lys Leu Val Arg Ala Glu Gln Ile Val Pro Leu Set Ala166016651670GCA AGC TTT GAA AGA GGC TCC TAC CAA CGA GGA TAT GAA TAT ATT GTG 5393Ala Ser Phe Glu Arg Gly Ser Tyr Gln Arg Gly Tyr Glu Tyr Ile Val167516801685AGA TTG CAC ATG TTA TGT GAG TTG GAG CAT AGC ATC AAA CCA CTT TTC 5441Arg Leu His Met Leu Cys Glu Leu Glu His Ser Ile Lys Pro Leu Phe169016951700CAG CAT TCT CCA GGT GAC AGT TCT CAA GAA GAT TCT CTA AAC TGG GTA 5489Gln His Ser Pro Gly Asp Ser Ser Gln Glu Asp Ser Leu Asn Trp Val170517101715GCT CGA CTA GAA ATG ACC CAG AAT TCC TAC AGA GCC AAG GAG CCT ATC 5537Ala Arg Leu Glu Met Thr Gln Asn Ser Tyr Arg Ala Lys Glu Pro Ile1720172517301735CTG GCT CTC CGG AGG GCT TTA CTA AGC CTC AAC AAA AGA CCA GAT TAC 5585Leu Ala Leu Arg Arg Ala Leu Leu Ser Leu Asn Lys Arg Pro Asp Tyr174017451750AAT GAA ATG GTT GGA GAA TGC TGG CTG CAG AGT GCC AGG GTA GCT AGA 5633Asn Glu Met Val Gly Glu Cys Trp Leu Gln Ser Ala Arg Val Ala Arg175517601765AAG GCT GGT CAC CAC CAG ACA GCC TAC AAT GCT CTC CTT AAT GCA GGG 5681Lys Ala Gly His His Gln Thr Ala Tyr Asn Ala Leu Leu Asn Ala Gly177017751780GAA TCA CGA CTC GCT GAA CTG TAC GTG GAA AGG GCA AAG TGG CTC TGG 5729Glu Ser Arg Leu Ala Glu Leu Tyr Val Glu Arg Ala Lys Trp Leu Trp178517901795TCC AAG GGT GAT GTT CAC CAG GCA CTA ATT GTT CTT CAA AAA GGT GTT 5777Ser Lys Gly Asp Val His Gln Ala Leu Ile Val Leu Gln Lys Gly Val1800180518101815GAA TTA TGT TTT CCT GAA AAT GAA ACC CCA CCT GAG GGT AAG AAC ATG 5825Glu Leu Cys Phe Pro Glu Asn Glu Thr Pro Pro Glu Gly Lys Asn Met182018251830TTA ATC CAT GGT CGA GCT ATG CTA CTA GTG GGC CGA TTT ATG GAA GAA 5873Leu Ile His Gly Arg Ala Met Leu Leu Val Gly Arg Phe Met Glu Glu183518401845ACA GCT AAC TTT GAA AGC AAT GCA ATT ATG AAA AAA TAT AAG GAT GTG 5921Thr Ala Asn Phe Glu Ser Asn Ala Ile Met Lys Lys Tyr Lys Asp Val185018551860ACC GCG TGC CTG CCA GAA TGG GAG GAT GGG CAT TTT TAC CTT GCC AAG 5969Thr Ala Cys Leu Pro Glu Trp Glu Asp Gly His Phe Tyr Leu Ala Lys186518701875TAC TAT GAC AAA TTG ATG CCC ATG GTC ACA GAC AAC AAA ATG GAA AAG 6017Tyr Tyr Asp Lys Leu Met Pro Met Val Thr Asp Asn Lys Met Glu Lys1880188518901895CAA GGT GAT CTC ATC CGG TAT ATA GTT CTT CAT TTT GGC AGA TCT CTA 6065Gln Gly Asp Leu Ile Arg Tyr Ile Val Leu His Phe Gly Arg Ser Leu190019051910CAA TAT GGA AAT CAG TTC ATA TAT CAG TCA ATG CCA CGA ATG TTA ACT 6113Gln Tyr Gly Asn Gln Phe Ile Tyr Gln Ser Met Pro Arg Met Leu Thr191519201925CTA TGG CTT GAT TAT GGT ACA AAG GCA TAT GAA TGG GAA AAA GCT GGC 6161Leu Trp Leu Asp Tyr Gly Thr Lys Ala Tyr Glu Trp Glu Lys Ala Gly193019351940CGC TCC GAT CGT GTA CAA ATG AGG AAT GAT TTG GGT AAA ATA AAC AAG 6209Arg Ser Asp Arg Val Gln Met Arg Asn Asp Leu Gly Lys Ile Asn Lys194519501955GTT ATC ACA GAG CAT ACA AAC TAT TTA GCT CCA TAT CAA TTT TTG ACT 6257Val Ile Thr Glu His Thr Asn Tyr Leu Ala Pro Tyr Gln Phe Leu Thr1960196519701975GCT TTT TCA CAA TTG ATC TCT CGA ATT TGT CAT TCT CAC GAT GAA GTT 6305Ala Phe Ser Gln Leu Ile Ser Arg Ile Cys His Ser His Asp Glu Val198019851990TTT GTT GTG CTT GAT GGA AAT AAT AGC CAA GTA TTT CTA GCC TAT CCT 6353Phe Val Val Leu Asp Gly Asn Asn Ser Gln Val Phe Leu Ala Tyr Pro199520002005CAA CAA GCA ATG TGG ATG ATG ACA GCT GTG TCA AAG TCA TCT TAT CCC 6401Gln Gln Ala Met Trp Met Met Thr Ala Val Ser Lys Ser Ser Tyr Pro201020152020ATG CGT GTG AAC AGA TGC AAG GAA ATC CTC AAT AAA GCT ATT CAT ATG 6449Met Arg Val Asn Arg Cys Lys Glu Ile Leu Asn Lys Ala Ile His Met202520302035AAA AAA TCC TTA GAG AAG TTT GTT GGA GAT GCA ACT CGC CTA ACA GAT 6497Lys Lys Ser Leu Glu Lys Phe Val Gly Asp Ala Thr Arg Leu Thr Asp2040204520502055AAG CTT CTA GAA TTG TGC AAT AAA CCG GTG GAA ATT CTT GCT TCT CTT 6545Lys Leu Leu Glu Leu Cys Asn Lys Pro Val Glu Ile Leu Ala Ser Leu206020652070CAG AAA CCA AAG AAG ATT TCT TTA AAA GGC TCA GAT GGA AAG TTC TAC 6593Gln Lys Pro Lys Lys Ile Ser Leu Lys Gly Ser Asp Gly Lys Phe Tyr207520802085ATC ATG ATG TGT AAG CCA AAA GAT GAC CTG AGA AAG GAT TGT AGA CTA 6641Ile Met Met Cys Lys Pro Lys Asp Asp Leu Arg Lys Asp Cys Arg Leu209020952100ATG GAA TTC AAT TCC TTG ATT AAT AAG TGC TTA AGA AAA GAT GCA GAG 6689Met Glu Phe Asn Ser Leu Ile Asn Lys Cys Leu Arg Lys Asp Ala Glu210521102115TCT CGT AGA AGA GAA CTT CAT ATT CGA ACA TAT GCA GTT ATT CCA CTA 6737Ser Arg Arg Arg Glu Leu His Ile Arg Thr Tyr Ala Val Ile Pro Leu2120212521302135AAT GAT GAA TGT GGG ATT ATT GAA TGG GTG AAC AAC ACT GCT GGT TTG 6785Asn Asp Glu Cys Gly Ile Ile Glu Trp Val Asn Asn Thr Ala Gly Leu214021452150AGA CCT ATT CTG ACC AAA CTA TAT AAA GAA AAG GGA GTG TAT ATG ACA 6833Arg Pro Ile Leu Thr Lys Leu Tyr Lys Glu Lys Gly Val Tyr Met Thr215521602165GGA AAA GAA CTT CGC CAG TGT ATG CTA CCA AAG TCA GCA GCT TTA TCT 6881Gly Lys Glu Leu Arg Gln Cys Met Leu Pro Lys Ser Ala Ala Leu Ser217021752180GAA AAA CTC AAA GTA TTC CGA GAA TTT CTC CTG CCC AGG CAT CCT CCT 6929Glu Lys Leu Lys Val Phe Arg Glu Phe Leu Leu Pro Arg His Pro Pro218521902195ATT TTT CAT GAG TGG TTT CTG AGA ACA TTC CCT GAT CCT ACA TCA TGG 6977Ile Phe His Glu Trp Phe Leu Arg Thr Phe Pro Asp Pro Thr Ser Trp2200220522102215TAC AGT AGT AGA TCA GCT TAC TGC CGT TCC ACT GCA GTA ATG TCA ATG 7025Tyr Ser Ser Arg Ser Ala Tyr Cys Arg Ser Thr Ala Val Met Ser Met222022252230GTT GGT TAT ATT CTG GGG CTT GGA GAC CGT CAT GGT GAA AAT ATT CTC 7073Val Gly Tyr Ile Leu Gly Leu Gly Asp Arg His Gly Glu Asn Ile Leu223522402245TTT GAT TCT TTG ACT GGT GAA TGC GTA CAT GTA GAT TTC AAT TGT CTT 7121Phe Asp Ser Leu Thr Gly Glu Cys Val His Val Asp Phe Asn Cys Leu225022552260TTC AAT AAG GGA GAA ACC TTT GAA GTT CCA GAA ATT GTG CCA TTT CGC 7169Phe Asn Lys Gly Glu Thr Phe Glu Val Pro Glu Ile Val Pro Phe Arg226522702275CTG ACT CAT AAT ATG GTT AAT GGA ATG GGT CCT ATG GGA ACA GAG GGT 7217Leu Thr His Asn Met Val Asn Gly Met Gly Pro Met Gly Thr Glu Gly2280228522902295CTT TTT CGA AGA GCA TGT GAA GTT ACA ATG AGG CTG ATG CGT GAT CAG 7265Leu Phe Arg Arg Ala Cys Glu Val Thr Met Arg Leu Met Arg Asp Gln230023052310CGA GAG CCT TTA ATG AGT GTC TTA AAG ACT TTT CTA CAT GAT CCT CTT 7313Arg Glu Pro Leu Met Ser Val Leu Lys Thr Phe Leu His Asp Pro Leu231523202325GTG GAA TGG AGT AAA CCA GTG AAA GGG CAT TCC AAA GCG CCA CTG AAT 7361Val Glu Trp Ser Lys Pro Val Lys Gly His Ser Lys Ala Pro Leu Asn233023352340GAA ACT GGA GAA GTT GTC AAT GAA AAG GCC AAG ACC CAT GTT CTT GAC 7409Glu Thr Gly Glu Val Val Asn Glu Lys Ala Lys Thr His Val Leu Asp234523502355ATT GAG CAG CGA CTA CAA GGT GTA ATC AAG ACT CGA AAT AGA GTG ACA 7457Ile Glu Gln Arg Leu Gln Gly Val Ile Lys Thr Arg Asn Arg Val Thr2360236523702375GGA CTG CCG TTA TCT ATT GAA GGA CAT GTG CAT TAC CTT ATA CAA GAA 7505Gly Leu Pro Leu Ser Ile Glu Gly His Val His Tyr Leu Ile Gln Glu238023852390GCT ACT GAT GAA AAC TTA CTA TGC CAG ATG TAT CTT GGT TGG ACT CCA 7553Ala Thr Asp Glu Asn Leu Leu Cys Gln Met Tyr Leu Gly Trp Thr Pro239524002405TAT ATG TGAAATGAAA TTATGTAAAA GAATATGTTA ATAATCTAAA AGTAAAAAAA 7609Tyr MetAAAAAAAAAA AA7621(2)SEQ ID NO2的说明(i)序列特征(A)长度2409个氨基酸(B)类型氨基酸(D)拓扑结构线性(ii)分子类型蛋白(xi)序列描述SEQ ID NO2Met Gly His Ala Val Glu Trp Pro Val Val Met Ser Arg Phe Leu Ser1 5 10 15Gln Leu Asp Glu His Met Gly Tyr Leu Gln Ser Ala Pro Leu Gln Leu20 25 30Met Ser Met Gln Lys Leu Glu Phe Ile Glu Val Thr Leu Leu Thr Val35 40 45Leu Thr Arg Ile Ile Ala Ile Val Phe Phe Arg Arg Gln Glu Leu Leu50 55 60Leu Trp Gln Ile Gly Cys Val Leu Leu Glu Tyr Gly Ser Pro Lys Ile65 70 75 80Lys Ser Leu Ala Ile Ser Phe Leu Thr Glu Leu Phe Gln Leu Gly Gly85 90 95Leu Pro Ala Gln Pro Ala Ser Thr Phe Phe Ser Ser Phe Leu Glu Leu100 105 110Leu Lys His Leu Val Glu Met Asp Thr Asp Gln Leu Lys Leu Tyr Glu115 120 125Glu Pro Leu Ser Lys Leu Ile Lys Thr Leu Phe Pro Phe Glu Ala Glu130 135 140Ala Tyr Arg Asn Ile Glu Pro Val Tyr Leu Asn Met Leu Leu Glu Lys145 150 155 160Leu Cys Val Met Phe Glu Asp Gly Val Leu Met Arg Leu Lys Ser Asp165 170 175Leu Leu Lys Ala Ala Leu Cys His Leu Leu Gln Tyr Phe Leu Lys Phe180 185 190Val Pro Ala Gly Tyr Glu Ser Ala Leu Gln Val Arg Lys Val Tyr Val195 200 205Arg Asn Ile Cys Lys Ala Leu Leu Asp Val Leu Gly Ile Glu Val Asp210 215 220Ala Glu Tyr Leu Leu Gly Pro Leu Tyr Ala Ala Leu Lys Met Glu Ser225 230 235 240Met Glu Ile Ile Glu Glu Ile Gln Cys Gln Thr Gln Gln Glu Asn Leu245 250 255Ser Ser Asn Ser Asp Gly Ile Ser Pro Lys Arg Arg Arg Leu Ser Ser260 265 270Ser Leu Asn Pro Ser Lys Arg Ala Pro Lys Gln Thr Glu Glu Ile Lys275 280 285His Val Asp Met Asn Gln Lys Ser Ile Leu Trp Ser Ala Leu Lys Gln290 295 300Lys Ala Glu Ser Leu Gln Ile Ser Leu Glu Tyr Ser Gly Leu Lys Asn305 310 315 320Pro Val Ile Glu Met Leu Glu Gly Ile Ala Val Val Leu Gln Leu Thr325 330 335Ala Leu Cys Thr Val His Cys Ser His Gln Asn Met Asn Cys Arg Thr340 345 350Phe Lys Asp Cys Gln His Lys Ser Lys Lys Lys Pro Ser Val Val Ile355 360 365Thr Trp Met Ser Leu Asp Phe Tyr Thr Thr Val Leu Lys Ser Cys Arg370 375 380Arg Leu Leu Glu Ser Val Gln Lys Arg Thr Gly Gly Asn Ile Asp Lys385 390 395 400Val Val Lys Ile Tyr Asp Ala Leu Ile Tyr Met Gln Val Asn Ser Ser405 410 415Phe Glu Asp His Ile Leu Glu Asp Leu Cys Gly Met Leu Ser Leu Pro420 425 430Trp Ile Tyr Ser His Ser Asp Asp Gly Cys Leu Lys Leu Thr Thr Phe435 440 445Ala Ala Asn Leu Leu Thr Leu Ser Cys Arg Ile Ser Asp Ser Tyr Ser450 455 460Pro Gln Ala Gln Ser Arg Cys Val Phe Leu Leu Thr Leu Phe Pro Arg465 470 475 480Arg Ile Phe Leu Glu Trp Arg Thr Ala Val Tyr Asn Trp Ala Leu Gln485 490 495Ser Ser His Glu Val Ile Arg Ala Ser Cys Val Ser Gly Phe Phe Ile500 505 510Leu Leu Gln Gln Gln Asn Ser Cys Asn Arg Val Pro Lys Ile Leu Ile515 520 525Asp Lys Val Lys Asp Asp Ser Asp Ile Val Lys Lys Glu Phe Ala Ser530 535 540Ile Leu Gly Gln Leu Val Cys Thr Leu His Gly Met Phe Tyr Leu Thr545 550 555 560Ser Ser Leu Thr Glu Pro Phe Ser Glu His Gly His Val Asp Leu Phe565 570 575Cys Arg Asn Leu Lys Ala Thr Ser Gln His Glu Cys Ser Ser Ser Gln580 585 590Leu Lys Ala Ser Val Cys Lys Pro Phe Leu Phe Leu Leu Lys Lys Lys595 600 605Ile Pro Ser Pro Val Lys Leu Ala Phe Ile Asp Asn Leu His His Leu610 615 620Cys Lys His Leu Asp Phe Arg Glu Asp Glu Thr Asp Val Lys Ala Val625 630 635 640Leu Gly Thr Leu Leu Asn Leu Met Glu Asp Pro Asp Lys Asp Val Arg645 650 655Val Ala Phe Ser Gly Asn Ile Lys His Ile Leu Glu Ser Leu Asp Ser660 665 670Glu Asp Gly Phe Ile Lys Glu Leu Phe Val Leu Arg Met Lys Glu Ala675 680 685Tyr Thr His Ala Gln Ile Ser Arg Asn Asn Glu Leu Lys Asp Thr Leu690 695 700Ile Leu Thr Thr Gly Asp Ile Gly Arg Ala Ala Lys Gly Asp Leu Val705 710 715 720Pro Phe Ala Leu Leu His Leu Leu His Cys Leu Leu Ser Lys Ser Ala725 730 735Ser Val Ser Gly Ala Ala Tyr Thr Glu Ile Arg Ala Leu Val Ala Ala740 745 750Lys Ser Val Lys Leu Gln Ser Phe Phe Ser Gln Tyr Lys Lys Pro Ile755 760 765Cys Gln Phe Leu Val Glu Ser Leu His Ser Ser Gln Met Thr Ala Leu770 775 780Pro Asn Thr Pro Cys Gln Asn Ala Asp Val Arg Lys Gln Asp Val Ala785 790 795 800His Gln Arg Glu Met Ala Leu Asn Thr Leu Ser Glu Ile Ala Asn Val805 810 815Phe Asp Phe Pro Asp Leu Asn Arg Phe Leu Thr Arg Thr Leu Gln Val820 825 830Leu Leu Pro Asp Leu Ala Ala Lys Ala Ser Pro Ala Ala Ser Ala Leu835 840 845Ile Arg Thr Leu Gly Lys Gln Leu Asn Val Asn Arg Arg Glu Ile Leu850 855 860Ile Asn Asn Phe Lys Tyr Ile Phe Ser His Leu Val Cys Ser Cys Ser865 870 875 880Lys Asp Glu Leu Glu Arg Ala Leu His Tyr Leu Lys Asn Glu Thr Glu885 890 895Ile Glu Leu Gly Ser Leu Leu Arg Gln Asp Phe Gln Gly Leu His Asn900 905 910Glu Leu Leu Leu Arg Ile Gly Glu His Tyr Gln Gln Val Phe Asn Gly915 920 925Leu Ser Ile Leu Ala Ser Phe Ala Ser Ser Asp Asp Pro Tyr Gln Gly930 935 940Pro Arg Asp Ile Ile Ser Pro Glu Leu Met Ala Asp Tyr Leu Gln Pro945 950 955 960Lys Leu Leu Gly Ile Leu Ala Phe Phe Asn Met Gln Leu Leu Ser Ser965 970 975Ser Val Gly Ile Glu Asp Lys Lys Met Ala Leu Asn Ser Leu Met Ser980 985 990Leu Met Lys Leu Met Gly Pro Lys His Val Ser Ser Val Arg Val Lys995 10001005Met Met Thr Thr Leu Arg Thr Gly Leu Arg Phe Lys Asp Asp Phe Pro101010151020Glu Leu Cys Cys Arg Ala Trp Asp Cys Phe Val Arg Cys Leu Asp His1025103010351040Ala Cys Leu Gly Ser Leu Leu Ser His Val Ile Val Ala Leu Leu Pro104510501055Leu Ile His Ile Gln Pro Lys Glu Thr Ala Ala Ile Phe His Tyr Leu106010651070Ile Ile Glu Asn Arg Asp Ala Val Gln Asp Phe Leu His Glu Ile Tyr107510801085Phe Leu Pro Asp His Pro Glu Leu Lys Lys Ile Lys Ala Val Leu Gln109010951100Glu Tyr Arg Lys Glu Thr Ser Glu Ser Thr Asp Leu Gln Thr Thr Leu1105111011151120Gln Leu Ser Met Lys Ala Ile Gln His Glu Asn Val Asp Val Arg Ile112511301135His Ala Leu Thr Ser Leu Lys Glu Thr Leu Tyr Lys Asn Gln Glu Lys114011451150Leu Ile Lys Tyr Ala Thr Asp Ser Glu Thr Val Glu Pro Ile Ile Ser115511601165Gln Leu Val Thr Val Leu Leu Lys Gly Cys Gln Asp Ala Asn Ser Gln117011751180Ala Arg Leu Leu Cys Gly Glu Cys Leu Gly Glu Leu Gly Ala Ile Asp1185119011951200Pro Gly Arg Leu Asp Phe Ser Thr Thr Glu Thr Gln Gly Lys Asp Phe120512101215Thr Phe Val Thr Gly Val Glu Asp Ser Ser Phe Ala Tyr Gly Leu Leu122012251230Met Glu Leu Thr Arg Ala Tyr Leu Ala Tyr Ala Asp Asn Ser Arg Ala123512401245Pro Asp Ser Ala Ala Tyr Ala Ile Gln Glu Leu Leu Ser Ile Tyr Asp125012551260Cys Arg Glu Met Glu Thr Asn Gly Pro Gly His Gln Leu Trp Arg Arg1265127012751280Phe Pro Glu His Val Arg Glu Ile Leu Glu Pro His Leu Asn Thr Arg128512901295Tyr Lys Ser Ser Gln Lys Ser Thr Asp Trp Ser Gly Val Lys Lys Pro130013051310Ile Tyr Leu Ser Lys Leu Gly Ser Asn Phe Ala Glu Trp Ser Ala Ser131513201325Trp Ala Gly Tyr Leu Ile Thr Lys Val Arg His Asp Leu Ala Ser Lys133013351340Ile Phe Thr Cys Cys Ser Ile Met Met Lys His Asp Phe Lys Val Thr1345135013551360Ile Tyr Leu Leu Pro His Ile Leu Val Tyr Val Leu Leu Gly Cys Asn136513701375Gln Glu Asp Gln Gln Glu Val Tyr Ala Glu Ile Met Ala Val Leu Lys138013851390His Asp Asp Gln His Thr Ile Asn Thr Gln Asp Ile Ala Ser Asp Leu139514001405Cys Gln Leu Ser Thr Gln Thr Val Phe Ser Met Leu Asp His Leu Thr141014151420Gln Trp Ala Arg His Lys Phe Gln Ala Leu Lys Ala Glu Lys Cys Pro1425143014351440His Ser Lys Ser Asn Arg Asn Lys Val Asp Ser Met Val Ser Thr Val144514501455Asp Tyr Glu Asp Tyr Gln Ser Val Thr Arg Phe Leu Asp Leu Ile Pro146014651470Gln Asp Thr Leu Ala Val Ala Ser Phe Arg Ser Lys Ala Tyr Thr Arg147514801485Ala Val Met His Phe Glu Ser Phe Ile Thr Glu Lys Lys Gln Asn Ile149014951500Gln Glu His Leu Gly Phe Leu Gln Lys Leu Tyr Ala Ala Met His Glu1505151015151520Pro Asp Gly Val Ser Gly Val Ser Ala Ile Arg Lys Ala Glu Pro Ser152515301535Leu Lys Glu Gln Ile Leu Glu His Glu Ser Leu Gly Leu Leu Arg Asp154015451550Ala Thr Ala Cys Tyr Asp Arg Ala Ile Gln Leu Glu Pro Asp Gln Ile155515601565Ile His Tyr His Gly Val Val Lys Ser Met Leu Gly Leu Gly Gln Leu157015751580Ser Thr Val Ile Thr Gln Val Asn Gly Val His Ala Asn Arg Ser Glu1585159015951600Trp Thr Asp Glu Leu Asn Thr Tyr Arg Val Glu Ala Ala Trp Lys Leu160516101615Ser Gln Trp Asp Leu Val Glu Asn Tyr Leu Ala Ala Asp Gly Lys Ser162016251630Thr Thr Trp Ser Val Arg Leu Gly Gln Leu Leu Leu Ser Ala Lys Lys163516401645Arg Asp Ile Thr Ala Phe Tyr Asp Ser Leu Lys Leu Val Arg Ala Glu165016551660Gln Ile Val Pro Leu Ser Ala Ala Ser Phe Glu Arg Gly Ser Tyr Gln1665167016751680Arg Gly Tyr Glu Tyr Ile Val Arg Leu His Met Leu Cys Glu Leu Glu168516901695His Ser Ile Lys Pro Leu Phe Gln His Ser Pro Gly Asp Ser Ser Gln170017051710Glu Asp Ser Leu Asn Trp Val Ala Arg Leu Glu Met Thr Gln Asn Ser171517201725Tyr Arg Ala Lys Glu Pro Ile Leu Ala Leu Arg Arg Ala Leu Leu Ser173017351740Leu Asn Lys Arg Pro Asp Tyr Asn Glu Met Val Gly Glu Cys Trp Leu1745175017551760Gln Ser Ala Arg Val Ala Arg Lys Ala Gly His His Gln Thr Ala Tyr176517701775Asn Ala Leu Leu Asn Ala Gly Glu Ser Arg Leu Ala Glu Leu Tyr Val178017851790Glu Arg Ala Lys Trp Leu Trp Ser Lys Gly Asp Val His Gln Ala Leu179518001805Ile Val Leu Gln Lys Gly Val Glu Leu Cys Phe Pro Glu Asn Glu Thr181018151820Pro Pro Glu Gly Lys Asn Met Leu Ile His Gly Arg Ala Met Leu Leu1825183018351840Val Gly Arg Phe Met Glu Glu Thr Ala Asn Phe Glu Ser Asn Ala Ile184518501855Met Lys Lys Tyr Lys Asp Val Thr Ala Cys Leu Pro Glu Trp Glu Asp186018651870Gly His Phe Tyr Leu Ala Lys Tyr Tyr Asp Lys Leu Met Pro Met Val187518801885Thr Asp Asn Lys Met Glu Lys Gln Gly Asp Leu Ile Arg Tyr Ile Val189018951900Leu His Phe Gly Arg Ser Leu Gln Tyr Gly Asn Gln Phe Ile Tyr Gln1905191019151920Ser Met Pro Arg Met Leu Thr Leu Trp Leu Asp Tyr Gly Thr Lys Ala192519301935Tyr Glu Trp Glu Lys Ala Gly Arg Ser Asp Arg Val Gln Met Arg Asn194019451950Asp Leu Gly Lys Ile Asn Lys Val Ile Thr Glu His Thr Asn Tyr Leu195519601965Ala Pro Tyr Gln Phe Leu Thr Ala Phe Ser Gln Leu Ile Ser Arg Ile197019751980Cys His Ser His Asp Glu Val Phe Val Val Leu Asp Gly Asn Asn Ser1985199019952000Gln Val Phe Leu Ala Tyr Pro Gln Gln Ala Met Trp Met Met Thr Ala200520102015Val Ser Lys Ser Ser Tyr Pro Met Arg Val Asn Arg Cys Lys Glu Ile202020252030Leu Asn Lys Ala Ile His Met Lys Lys Ser Leu Glu Lys Phe Val Gly203520402045Asp Ala Thr Arg Leu Thr Asp Lys Leu Leu Glu Leu Cys Asn Lys Pro205020552060Val Glu Ile Leu Ala Ser Leu Gln Lys Pro Lys Lys Ile Ser Leu Lys2065207020752080Gly Ser Asp Gly Lys Phe Tyr Ile Met Met Cys Lys Pro Lys Asp Asp208520902095Leu Arg Lys Asp Cys Arg Leu Met Glu Phe Asn Ser Leu Ile Asn Lys210021052110Cys Leu Arg Lys Asp Ala Glu Ser Arg Arg Arg Glu Leu His Ile Arg211521202125Thr Tyr Ala Val Ile Pro Leu Asn Asp Glu Cys Gly Ile Ile Glu Trp213021352140Val Asn Asn Thr Ala Gly Leu Arg Pro Ile Leu Thr Lys Leu Tyr Lys2145215021552160Glu Lys Gly Val Tyr Met Thr Gly Lys Glu Leu Arg Gln Cys Met Leu216521702175Pro Lys Ser Ala Ala Leu Ser Glu Lys Leu Lys Val Phe Arg Glu Phe218021852190Leu Leu Pro Arg His Pro Pro Ile Phe His Glu Trp Phe Leu Arg Thr219522002205Phe Pro Asp Pro Thr Ser Trp Tyr Ser Ser Arg Ser Ala Tyr Cys Arg221022152220Ser Thr Ala Val Met Ser Met Val Gly Tyr Ile Leu Gly Leu Gly Asp2225223022352240Arg His Gly Glu Asn Ile Leu Phe Asp Ser Leu Thr Gly Glu Cys Val224522502255His Val Asp Phe Asn Cys Leu Phe Asn Lys Gly Glu Thr Phe Glu Val226022652270Pro Glu Ile Val Pro Phe Arg Leu Thr His Asn Met Val Asn Gly Met227522802285Gly Pro Met Gly Thr Glu Gly Leu Phe Arg Arg Ala Cys Glu Val Thr229022952300Met Arg Leu Met Arg Asp Gln Arg Glu Pro Leu Met Ser Val Leu Lys2305231023152320Thr Phe Leu His Asp Pro Leu Val Glu Trp Ser Lys Pro Val Lys Gly232523302335His Ser Lys Ala Pro Leu Asn Glu Thr Gly Glu Val Val Asn Glu Lys234023452350Ala Lys Thr His Val Leu Asp Ile Glu Gln Arg Leu Gln Gly Val Ile235523602365Lys Thr Arg Asn Arg Val Thr Gly Leu Pro Leu Ser Ile Glu Gly His237023752380Val His Tyr Leu Ile Gln Glu Ala Thr Asp Glu Asn Leu Leu Cys Gln2385239023952400Met Tyr Leu Gly Trp Thr Pro Tyr Met2405(2)SEQ ID NO3的说明(i)序列特征(A)长度2835个碱基对(B)类型核苷酸(C)链型单链(D)拓扑结构线性(ii)分子类型cDNA(vii)直接来源(B)克隆517(ix)特征(A)姓名/符号CDS(B)位置1..2610(xi)序列描述SEQ ID NO3GTG GAA GCA GCT TGG AAA TTG TCA CAG TGG GAT TTG GTG GAA AAC TAT 48Val Glu Ala Ala Trp Lys Leu Ser Gln Trp Asp Leu Val Glu Asn Tyr1 5 10 15TTG GCA GCA GAT GGA AAA TCT ACA ACA TGG AGT GTC AGA CTG GGA CAG 96Leu Ala Ala Asp Gly Lys Ser Thr Thr Trp Ser Val Arg Leu Gly Gln20 25 30CTA TTA TTA TCA GCC AAA AAA AGA GAT ATC ACA GCT TTT TAT GAC TCA 144Leu Leu Leu Ser Ala Lys Lys Arg Asp Ile Thr Ala Phe Tyr Asp Ser35 40 45CTG AAA CTA GTG AGA GCA GAA CAA ATT GTA CCT CTT TCA GCT GCA AGC 192Leu Lys Leu Val Arg Ala Glu Gln Ile Val Pro Leu Ser Ala Ala Ser50 55 60TTT GAA AGA GGC TCC TAC CAA CGA GGA TAT GAA TAT ATT GTG AGA TTG 240Phe Glu Arg Gly Ser Tyr Gln Arg Gly Tyr Glu Tyr Ile Val Arg Leu65 70 75 80CAC ATG TTA TGT GAG TTG GAG CAT AGC ATC AAA CCA CTT TTC CAG CAT 288His Met Leu Cys Glu Leu Glu His Ser Ile Lys Pro Leu Phe Gln His85 90 95TCT CCA GGT GAC AGT TCT CAA GAA GAT TCT CTA AAC TGG GTA GCT CGA 336Ser Pro Gly Asp Ser Ser Gln Glu Asp Ser Leu Asn Trp Val Ala Arg100 105 110CTA GAA ATG ACC CAG AAT TCC TAC AGA GCC AAG GAG CCT ATC CTG GCT 384Leu Glu Met Thr Gln Asn Ser Tyr Arg Ala Lys Glu Pro Ile Leu Ala115 120 125CTC CGG AGG GCT TTA CTA AGC CTC AAC AAA AGA CCA GAT TAC AAT GAA 432Leu Arg Arg Ala Leu Leu Ser Leu Asn Lys Arg Pro Asp Tyr Asn Glu130 135 140ATG GTT GGA GAA TGC TGG CTG CAG AGT GCC AGG GTA GCT AGA AAG GCT 480Met Val Gly Glu Cys Trp Leu Gln Ser Ala Arg Val Ala Arg Lys Ala145 150 155 160GGT CAC CAC CAG ACA GCC TAC AAT GCT CTC CTT AAT GCA GGG GAA TCA 528Gly His His Gln Thr Ala Tyr Asn Ala Leu Leu Asn Ala Gly Glu Ser165 170 175CGA CTC GCT GAA CTG TAC GTG GAA AGG GCA AAG TGG CTC TGG TCC AAG 576Arg Leu Ala Glu Leu Tyr Val Glu Arg Ala Lys Trp Leu Trp Ser Lys180 185 190GGT GAT GTT CAC CAG GCA CTA ATT GTT CTT CAA AAA GGT GTT CAA TTA 624Gly Asp Val His Gln Ala Leu Ile Val Leu Gln Lys Gly Val Glu Leu195 200 205TGT TTT CCT GAA AAT GAA ACC CCA CCT GAG GGT AAG AAC ATG TTA ATC 672Cys Phe Pro Glu Asn Glu Thr Pro Pro Glu Gly Lys Asn Met Leu Ile210 215 220CAT GGT CGA GCT ATG CTA CTA GTG GGC CGA TTT ATG GAA GAA ACA GCT 720His Gly Arg Ala Met Leu Leu Val Gly Arg Phe Met Glu Glu Thr Ala225 230 235 240AAC TTT GAA AGC AAT GCA ATT ATG AAA AAA TAT AAG GAT GTG ACC GCG 768Asn Phe Glu Ser Asn Ala Ile Met Lys Lys Tyr Lys Asp Val Thr Ala245 250 255TGC CTG CCA GAA TGG GAG GAT GGG CAT TTT TAC CTT GCC AAG TAC TAT 816Cys Leu Pro Glu Trp Glu Asp Gly His Phe Tyr Leu Ala Lys Tyr Tyr260 265 270GAC AAA TTG ATG CCC ATG GTC ACA GAC AAC AAA ATG GAA AAG CAA GGT 864Asp Lys Leu Met Pro Met Val Thr Asp Asn Lys Met Glu Lys Gln Gly275 280 285GAT CTC ATC CGG TAT ATA GTT CTT CAT TTT GGC AGA TCT CTA CAA TAT 912Asp Leu Ile Arg Tyr Ile Val Leu His Phe Gly Arg Ser Leu Gln Tyr290 295 300GGA AAT CAG TTC ATA TAT CAG TCA ATG CCA CGA ATG TTA ACT CTA TGG 960Gly Asn Gln Phe Ile Tyr Gln Ser Met Pro Arg Met Leu Thr Leu Trp305 310 315 320CTT GAT TAT GGT ACA AAG TCA TAT GAA TGG GAA AAA GCT GGC CGC TCC 1008Leu Asp Tyr Gly Thr Lys Ser Tyr Glu Trp Glu Lys Ala Gly Arg Ser325 330 335GAT CGT GTA CAA ATG AGG AAT GAT TTG GGT AAA ATA AAC AAG GTT ATC 1056Asp Arg Val Gln Met Arg Asn Asp Leu Gly Lys Ile Asn Lys Val Ile340 345 350ACA GAG CAT ACA AAC TAT TTA GCT CCA TAT CAA TTT TTG ACT GCT TTT 1104Thr Glu His Thr Asn Tyr Leu Ala Pro Tyr Gln Phe Leu Thr Ala Phe355 360 365TCA CAA TTG ATC TCT CGA ATT TGT CAT TCT CAC GAT GAA GTT TTT GTT 1152Ser Gln Leu Ile Ser Arg Ile Cys His Ser His Asp Glu Val Phe Val370 375 380GTC TTG ATG GAA ATA ATA GCC AAA GTA TTT CTA GCC TAT CCT CAA CAA 1200Val Leu Met Glu Ile Ile Ala Lys Val Phe Leu Ala Tyr Pro Gln Gln385 390 395 400GCA ATG TGG ATG ATG ACA GCT GTG TCA AAG TCA TCT TAT CCC ATG CGT 1248Ala Met Trp Met Met Thr Ala Val Ser Lys Ser Ser Tyr Pro Met Arg405 410 415GTG AAC AGA TGC AAG GAA ATC CTC AAT AAA GCT ATT CAT ATG AAA AAA 1296Val Asn Arg Cys Lys Glu Ile Leu Asn Lys Ala Ile His Met Lys Lys420 425 430TCC TTA GAG AAG TTT GTT GGA GAT GCA ACT CGC CTA ACA GAT AAG CTT 1344Ser Leu Glu Lys Phe Val Gly Asp Ala Thr Arg Leu Thr Asp Lys Leu435 440 445CTA GAA TTG TGC AAT AAA CCG GTT GAT GGA AGT AGT TCC ACA TTA AGC 1392Leu Glu Leu Cys Asn Lys Pro Val Asp Gly Ser Ser Ser Thr Leu Ser450 455 460ATG AGC ACT CAT TTT AAA ATG CTT AAA AAG CTG GTA GAA GAA GCA ACA 1440Met Ser Thr His Phe Lys Met Leu Lys Lys Leu Val Glu Glu Ala Thr465 470 475 480TTT AGT GAA ATC CTC ATT CCT CTA CAA TCA GTC ATG ATA CCT ACA CTT 1488Phe Ser Glu Ile Leu Ile Pro Leu Gln Ser Val Met Ile Pro Thr Leu485 490 495CCA TCA ATT CTG GGT ACC CAT GCT AAC CAT GCT AGC CAT GAA CCA TTT 1536Pro Ser Ile Leu Gly Thr His Ala Asn His Ala Ser His Glu Pro Phe500 505 510CCT GGA CAT TGG GCC TAT ATT GCA GGG TTT GAT GAT ATG GTG GAA ATT 1584Pro Gly His Trp Ala Tyr Ile Ala Gly Phe Asp Asp Met Val Glu Ile515 520 525CTT GCT TCT CTT CAG AAA CCA AAG AAG ATT TCT TTA AAA GGC TCA GAT 1632Leu Ala Ser Leu Gln Lys Pro Lys Lys Ile Ser Leu Lys Gly Ser Asp530 535 540GGA AAG TTC TAC ATC ATG ATG TGT AAG CCA AAA GAT GAC CTG AGA AAG 1680Gly Lys Phe Tyr Ile Met Met Cys Lys Pro Lys Asp Asp Leu Arg Lys545 550 555 560GAT TGT AGA CTA ATG GAA TTC AAT TCC TTG ATT AAT AAG TGC TTA AGA 1728Asp Cys Arg Leu Met Glu Phe Asn Ser Leu Ile Asn Lys Cys Leu Arg565 570 575AAA GAT GCA GAG TCT CGT AGA AGA GAA CTT CAT ATT CGA ACA TAT GCA 1776Lys Asp Ala Glu Ser Arg Arg Arg Glu Leu His Ile Arg Thr Tyr Ala580 585 590GTT ATT CCA CTA AAT GAT GAA TGT GGG ATT ATT GAA TGG GTG AAC AAC 1824Val Ile Pro Leu Asn Asp Glu Cys Gly Ile Ile Glu Trp Val Asn Asn595 600 605ACT GCT GGT TTG AGA CCT ATT CTG ACC AAA CTA TAT AAA GAA AAG GGA 1872Thr Ala Gly Leu Arg Pro Ile Leu Thr Lys Leu Tyr Lys Glu Lys Gly610 615 620GTG TAT ATG ACA GGA AAA GAA CTT CGC CAG TGT ATG CTA CCA AAG TCA 1920Val Tyr Met Thr Gly Lys Glu Leu Arg Gln Cys Met Leu Pro Lys Ser625 630 635 640GCA GCT TTA TCT GAA AAA CTC AAA GTA TTC CGA GAA TTT CTC CTG CCC 1968Ala Ala Leu Ser Glu Lys Leu Lys Val Phe Arg Glu Phe Leu Leu Pro645 650 655AGG CAT CCT CCT ATT TTT CAT GAG TGG TTT CTG AGA ACA TTC CCT GAT 2016Arg His Pro Pro Ile Phe His Glu Trp Phe Leu Arg Thr Phe Pro Asp660 665 670CCT ACA TCA TGG TAC AGT AGT AGA TCA GCT TAC TGC CGT TCC ACT GCA 2064Pro Thr Ser Trp Tyr Ser Ser Arg Ser Ala Tyr Cys Arg Ser Thr Ala675 680 685GTA ATG TCA ATG GTT GGT TAT ATT CTG GGG CTT GGA GAC CGT CAT GGT 2112Val Met Ser Met Val Gly Tyr Ile Leu Gly Leu Gly Asp Arg His Gly690 695 700GAA AAT ATT CTC TTT GAT TCT TTG ACT GGT GAA TGC GTA CAT GTA GAT 2160Glu Asn Ile Leu Phe Asp Ser Leu Thr Gly Glu Cys Val His Val Asp705 710 715 720TTC AAT TGT CTT TTC AAT AAG GGA GAA ACC TTT GAA GTT CCA GAA ATT 2208Phe Asn Cys Leu Phe Asn Lys Gly Glu Thr Phe Glu Val Pro Glu Ile725 730 735GTG CCA TTT CGC CTG ACT CAT AAT ATG GTT AAT GGA ATG GGT CCT ATG 2256Val Pro Phe Arg Leu Thr His Asn Met Val Asn Gly Met Gly Pro Met740 745 750GGA ACA GAG GGT CTT TTT CGA AGA GCA TGT GAA GTT ACA ATG AGG CTG 2304Gly Thr Glu Gly Leu Phe Arg Arg Ala Cys Glu Val Thr Met Arg Leu755 760 765ATG CGT GAT CAG CGA GAG CCT TTA ATG AGT GTC TTA AAG ACT TTT CTA 2352Met Arg Asp Gln Arg Glu Pro Leu Met Ser Val Leu Lys Thr Phe Leu770 775 780CAT GAT CCT CTT GTG GAA TGG AGT AAA CCA GTG AAA GGG CAT TCC AAA 2400His Asp Pro Leu Val Glu Trp Ser Lys Pro Val Lys Gly His Ser Lys785 790 795 800GCG CCA CTG AAT GAA ACT GGA GAA GTT GTC AAT GAA AAG GCC AAG ACC 2448Ala Pro Leu Asn Glu Thr Gly Glu Val Val Asn Glu Lys Ala Lys Thr805 810 815CAT GTT CTT GAC ATT GAG CAG CGA CTA CAA GGT GTA ATC AAG ACT CGA 2496His Val Leu Asp Ile Glu Gln Arg Leu Gln Gly Val Ile Lys Thr Arg820 825 830AAT AGA GTG ACA GGA CTG CCG TTA TCT ATT GAA GGA CAT GTG CAT TAC 2544Asn Arg Val Thr Gly Leu Pro Leu Ser Ile Glu Gly His Val His Tyr835 840 845CTT ATA CAA GAA GCT ACT GAT GAA AAC TTA CTA TGC CAG ATG TAT CTT 2592Leu Ile Gln Glu Ala Thr Asp Glu Asn Leu Leu Cys Gln Met Tyr Leu850 855 860GGT TGG ACT CCA TAT ATG TGAAATGAAA TTATGTAAAA GAATATGTTA2640Gly Trp Thr Pro Tyr Met865 870ATAATCTAAA AGTAATGCAT TTGGTATGAA TCTGTGGTTG TATCTGTTCA ATTCTAAAGT 2700ACAACATAAA TTTACGTTCT CAGCAACTGT TATTTCTCTC TGATCATTAA TTATATGTAA 2760AATAATATAC ATTCAGTTAT TAAGAAATAA ACTGCTTTCT TAATAAAAAA AAAAAAAAAA 2820AAAAAAAAAA AAAAA2835(2)SEQ ID NO4的说明(i)序列特征(A)长度870个氨基酸(B)类型氨基酸(D)拓扑结构线性(ii)分子类型蛋白(xi)序列描述SEQ ID NO4Val Glu Ala Ala Trp Lys Leu Ser Gln Trp Asp Leu Val Glu Asn Tyr1 5 10 15Leu Ala Ala Asp Gly Lys Ser Thr Thr Trp Ser Val Arg Leu Gly Gln20 25 30Leu Leu Leu Ser Ala Lys Lys Arg Asp Ile Thr Ala Phe Tyr Asp Ser35 40 45Leu Lys Leu Val Arg Ala Glu Gln Ile Val Pro Leu Ser Ala Ala Ser50 55 60Phe Glu Arg Gly Ser Tyr Gln Arg Gly Tyr Glu Tyr Ile Val Arg Leu65 70 75 80His Met Leu Cys Glu Leu Glu His Ser Ile Lys Pro Leu Phe Gln His85 90 95Ser Pro Gly Asp Ser Ser Gln Glu Asp Ser Leu Asn Trp Val Ala Arg100 105 110Leu Glu Met Thr Gln Asn Ser Tyr Arg Ala Lys Glu Pro Ile Leu Ala115 120 125Leu Arg Arg Ala Leu Leu Ser Leu Asn Lys Arg Pro Asp Tyr Asn Glu130 135 140Met Val Gly Glu Cys Trp Leu Gln Ser Ala Arg Val Ala Arg Lys Ala145 150 155 160Gly His His Gln Thr Ala Tyr Asn Ala Leu Leu Asn Ala Gly Glu Ser165 170 175Arg Leu Ala Glu Leu Tyr Val Glu Arg Ala Lys Trp Leu Trp Ser Lys180 185 190Gly Asp Val His Gln Ala Leu Ile Val Leu Gln Lys Gly Val Glu Leu195 200 205Cys Phe Pro Glu Asn Glu Thr Pro Pro Glu Gly Lys Asn Met Leu Ile210 215 220His Gly Arg Ala Met Leu Leu Val Gly Arg Phe Met Glu Glu Thr Ala225 230 235 240Asn Phe Glu Ser Asn Ala Ile Met Lys Lys Tyr Lys Asp Val Thr Ala245 250 255Cys Leu Pro Glu Trp Glu Asp Gly His Phe Tyr Leu Ala Lys Tyr Tyr260 265 270Asp Lys Leu Met Pro Met Val Thr Asp Asn Lys Met Glu Lys Gln Gly275 280 285Asp Leu Ile Arg Tyr Ile Val Leu His Phe Gly Arg Ser Leu Gln Tyr290 295 300Gly Asn Gln Phe Ile Tyr Gln Ser Met Pro Arg Met Leu Thr Leu Trp305 310 315 320Leu Asp Tyr Gly Thr Lys Ser Tyr Glu Trp Glu Lys Ala Gly Arg Ser325 330 335Asp Arg Val Gln Met Arg Asn Asp Leu Gly Lys Ile Asn Lys Val Ile340 345 350Thr Glu His Thr Asn Tyr Leu Ala Pro Tyr Gln Phe Leu Thr Ala Phe355 360 365Ser Gln Leu Ile Ser Arg Ile Cys His Ser His Asp Glu Val Phe Val370 375 380Val Leu Met Glu Ile Ile Ala Lys Val Phe Leu Ala Tyr Pro Gln Gln385 390 395 400Ala Met Trp Met Met Thr Ala Val Ser Lys Ser Ser Tyr Pro Met Arg405 410 415Val Asn Arg Cys Lys Glu Ile Leu Asn Lys Ala Ile His Met Lys Lys420 425 430Ser Leu Glu Lys Phe Val Gly Asp Ala Thr Arg Leu Thr Asp Lys Leu435 440 445Leu Glu Leu Cys Asn Lys Pro Val Asp Gly Ser Ser Ser Thr Leu Ser450 455 460Met Ser Thr His Phe Lys Met Leu Lys Lys Leu Val Glu Glu Ala Thr465 470 475 480Phe Ser Glu Ile Leu Ile Pro Leu Gln Ser Val Met Ile Pro Thr Leu485 490 495Pro Ser Ile Leu Gly Thr His Ala Asn His Ala Ser His Glu Pro Phe500 505 510Pro Gly His Trp Ala Tyr Ile Ala Gly Phe Asp Asp Met Val Glu Ile515 520 525Leu Ala Ser Leu Gln Lys Pro Lys Lys Ile Ser Leu Lys Gly Ser Asp530 535 540Gly Lys Phe Tyr Ile Met Met Cys Lys Pro Lys Asp Asp Leu Arg Lys545 550 555 560Asp Cys Arg Leu Met Glu Phe Asn Ser Leu Ile Asn Lys Cys Leu Arg565 570 575Lys Asp Ala Glu Ser Arg Arg Arg Glu Leu His Ile Arg Thr Tyr Ala580 585 590Val Ile Pro Leu Asn Asp Glu Cys Gly Ile Ile Glu Trp Val Asn Asn595 600 605Thr Ala Gly Leu Arg Pro Ile Leu Thr Lys Leu Tyr Lys Glu Lys Gly610 615 620Val Tyr Met Thr Gly Lys Glu Leu Arg Gln Cys Met Leu Pro Lys Ser625 630 635 640Ala Ala Leu Ser Glu Lys Leu Lys Val Phe Arg Glu Phe Leu Leu Pro645 650 655Arg His Pro Pro Ile Phe His Glu Trp Phe Leu Arg Thr Phe Pro Asp660 665 670Pro Thr Ser Trp Tyr Ser Ser Arg Ser Ala Tyr Cys Arg Ser Thr Ala675 680 685Val Met Ser Met Val Gly Tyr Ile Leu Gly Leu Gly Asp Arg His Gly690 695 700Glu Asn Ile Leu Phe Asp Ser Leu Thr Gly Glu Cys Val His Val Asp705 710 715 720Phe Asn Cys Leu Phe Asn Lys Gly Glu Thr Phe Glu Val Pro Glu Ile725 730 735Val Pro Phe Arg Leu Thr His Asn Met Val Asn Gly Met Gly Pro Met740 745 750Gly Thr Glu Gly Leu Phe Arg Arg Ala Cys Glu Val Thr Met Arg Leu755 760 765Met Arg Asp Gln Arg Glu Pro Leu Met Ser Val Leu Lys Thr Phe Leu770 775 780His Asp Pro Leu Val Glu Trp Ser Lys Pro Val Lys Gly His Ser Lys785 790 795 800Ala Pro Leu Asn Glu Thr Gly Glu Val Val Asn Glu Lys Ala Lys Thr805 810 815His Val Leu Asp Ile Glu Gln Arg Leu Gln GIy Val Ile Lys Thr Arg820 825 830Asn Arg Val Thr Gly Leu Pro Leu Ser Ile Glu Gly His Val His Tyr835 840 845Leu Ile Gln Glu Ala Thr Asp Glu Asn Leu Leu Cys Gln Met Tyr Leu850 855 860Gly Trp Thr Pro Tyr Met865 870(2)SEQ ID NO5的说明(i)序列特征(A)长度33碱基对(B)类型核苷酸(C)链型单链(D)拓扑结构线性(ii)分子类型DNA(vii)直接来源(B)克隆引物oDH15a(ix)特征(A)姓名/符号修饰的碱基(B)位置组(15，18，24，30)(D)其它资料在这些位置的核苷酸是肌苷。(xi)序列描述SEQ ID NO5GCAGACGGAT CCGGNWCNGA YGGNAAYHTN TAY 33(2)SEQ ID NO6的说明(i)序列特征(A)长度27个碱基对(B)类型核苷酸(C)链型单链(D)拓扑结构线性(ii)分子类型DNA(ix)特征(A)姓名/符号修饰的碱基(B)位置组(15，18，24)(D)其它资料在这些位置的核苷酸是肌苷。(xi)序列描述SEQ ID NO6GCAGACGGAT CCGGNWCNGA YGGNAAY27(2)SEQ ID NO7的说明(i)序列特征(A)长度30个碱基对(B)类型核苷酸(C)链型单链(D)拓扑结构线性(ii)分子类型DNA(vii)直接来源(B)克隆引物oDH16(ix)特征(A)姓名/符号修饰的碱基(B)位置24(D)其它资料在这些位置的核苷酸是肌苷。(xi)序列描述SEQ ID NO7GCAGACGAAT TCRCARTYRA ARTCNACRTG 30(2)SEQ ID NO8的说明(i)序列特征(A)长度41个碱基对(B)类型核苷酸(C)链型单链(D)拓扑结构线性(ii)分子类型DNA(vii)直接来源(B)克隆引物oDH17a(ix)特征(A)姓名/符号修饰的碱基(B)位置组(21，24，27，30)(D)其它资料在这些位置的核苷酸是肌苷。
(xi)序列描述SEQ ID NO8GCAGACGGAT CCAARTTYCC NCCNRTNYTN TAYSARTGGT T41(2)SEQ ID NO9的说明(i)序列特征(A)长度41个碱基对(B)类型核苷酸(C)链型单链(D)拓扑结构线性(ii)分子类型DNA(vii)直接来源(B)克隆引物oDH17b(ix)特征(A)姓名/符号修饰的碱基(B)位置组(24，27，30，33)(D)其它资料在这些位置的核苷酸是肌苷。(xi)序列描述SEQ ID NO9GCAGACGAAT CCAACCAYTS RTANARAYN GGNGGRAAYT T41(2)SEQ ID NO10的说明(i)序列特征(A)长度32个碱基对(B)类型核苷酸(C)链型单链(D)拓扑结构线性(ii)分子类型DNA(vii)直接来源(B)克隆引物oDH18a(ix)特征(A)姓名/符号修饰的碱基(B)位置组(15，18，21，24，30)(D)其它资料在这些位置的核苷酸是肌苷。(xi)序列描述SEQ ID NO10GCAGACGGAT CCYTNGGNYT NGGNGAYCGN CA 32(2)SEQ ID NO11的说明(i)序列特征(A)长度32个碱基对(B)类型核苷酸(C)链型单链(D)拓扑结构线性(ii)分子类型DNA(vii)直接来源(B)克隆引物oDH18b(ix)特征(A)姓名/符号修饰的碱基(B)位置组(15，18，21)(D)其它资料在这些位置的核苷酸是肌苷。(xi)序列描述SEQ ID NO11GCAGACGGAT CCYTNGGNYT NGGNGAYAGR CA 32(2)SEQ ID NO12的说明(i)序列特征(A)长度33个碱基对(B)类型核苷酸(C)链型单链(D)拓扑结构线性(ii)分子类型DNA(vii)直接来源(B)克隆引物oDH23(xi)序列描述SEQ ID NO12GACGCAGAAT TCACCAGTCA AAGAATCAAA GAG 33(2)SEQ ID NO13的说明(i)序列特征(A)长度16个碱基对(B)类型核苷酸(C)链型单链(D)拓扑结构线性(ii)分子类型DNA(vii)直接来源(B)克隆引物mo3(xi)序列描述SEQ ID NO13CTACAGAGCC AAGGAG16(2)SEQ ID NO14的说明(i)序列特征(A)长度22个碱基对(B)类型核苷酸(C)链型单链(D)拓扑结构线性(ii)分子类型DNA(vii)直接来源(B)克隆引物mo6(xi)序列描述SEQ ID NO14TCGAGCTATG CTACTAGTGG GC 22(2)SEQ ID NO15的说明(i)序列特征(A)长度17个碱基对(B)类型核苷酸(C)链型单链(D)拓扑结构线性(ii)分子类型DNA(vii)直接来源(B)克隆引物oHT9-1(xi)序列描述SEQ ID NO15CCAGTAAACT TGCTTTC 17(2)SEQ ID NO16的说明(i)序列特征(A)长度20个碱基对(B)类型核苷酸(C)链型单链(D)拓扑结构线性(ii)分子类型DNA(vii)直接来源(B)克隆引物oHT9-4(xi)序列描述SEQ ID NO16TTTGCGGCCC TTCCAATATC20(2)SEQ ID NO17的说明(i)序列特征(A)长度7440个碱基对(B)类型核苷酸(C)链型单链(D)拓扑结构线性(ii)分子类型cDNA(vii)直接来源(B)克隆MCCS1beta(ix)特征(A)姓名/符号CDS(B)位置1..7437(xi)序列描述SEQ ID NO17ATG GGT CAT GCT GTG GAA TGG CCA GTG GTC ATG AGC CGA TTT TTA AGT 48Met Gly His Ala Val Glu Trp Pro Val Val Met Ser Arg Phe Leu Ser1 5 10 15CAA TTA GAT GAA CAC ATG GGA TAT TTA CAA TCA GCT CCT TTG CAG TTG 96Gln Leu Asp Glu His Met Gly Tyr Leu Gln Ser Ala Pro Leu Gln Leu20 25 30ATG AGT ATG CAA AAA TTA GAA TTT ATT GAA GTC ACT TTA TTA ACG GTT 144Met Ser Met Gln Lys Leu Glu Phe Ile Glu Val Thr Leu Leu Thr Val35 40 45CTT ACT CGT ATT ATT GCA ATT GTG TTT TTT AGA AGG CAA GAA CTC TTA 192Leu Thr Arg Ile Ile Ala Ile Val Phe Phe Arg Arg Gln Glu Leu Leu50 55 60CTT TGG CAG ATA GGT TGT GTT CTG CTA GAG TAT GGT AGT CCA AAA ATT 240Leu Trp Gln Ile Gly Cys Val Leu Leu Glu Tyr Gly Ser Pro Lys Ile65 70 75 80AAA TCC CTA GCA ATT AGC TTT TTA ACA GAA CTT TTT CAG CTT GGA GGA 288Lys Ser Leu Ala Ile Ser Phe Leu Thr Glu Leu Phe Gln Leu Gly Gly85 90 95CTA CCA GCA CAA CCA GCT AGC ACT TTT TTC AGC TCA TTT TTG GAA TTA 336Leu Pro Ala Gln Pro Ala Ser Thr Phe Phe Ser Ser Phe Leu Glu Leu100 105 110TTA AAA CAC CTT GTA GAA ATG GAT ACT GAC CAA TTG AAA CTC TAT GAA 384Leu Lys His Leu Val Glu Met Asp Thr Asp Gln Leu Lys Leu Tyr Glu115 120 125GAG CCA TTA TCA AAG CTG ATA AAG ACA CTA TTT CCC TTT GAA GCA GAA 432Glu Pro Leu Ser Lys Leu Ile Lys Thr Leu Phe Pro Phe Glu Ala Glu130 135 140GCT TAT AGA AAT ATT GAA CCT GTC TAT TTA AAT ATG CTG CTG GAA AAA 480Ala Tyr Arg Asn Ile Glu Pro Val Tyr Leu Asn Met Leu Leu Glu Lys145 150 155 160CTC TGT GTC ATG TTT GAA GAC GGT GTG CTC ATG CGG CTT AAG TCT GAT 528Leu Cys Val Met Phe Glu Asp Gly Val Leu Met Arg Leu Lys Ser Asp165 170 175TTG CTA AAA GCA GCT TTG TGC CAT TTA CTG CAG TAT TTC CTT AAA TTT 576Leu Leu Lys Ala Ala Leu Cys His Leu Leu Gln Tyr Phe Leu Lys Phe180 185 190GTG CCA GCT GGG TAT GAA TCT GCT TTA CAA GTC AGG AAG GTC TAT GTG 624Val Pro Ala Gly Tyr Glu Ser Ala Leu Gln Val Arg Lys Val Tyr Val195 200 205AGA AAT ATT TGT AAA GCT CTT TTG GAT GTG CTT GGA ATT GAG GTA GAT 672Arg Asn Ile Cys Lys Ala Leu Leu Asp Val Leu Gly Ile Glu Val Asp210 215 220GCA GAG TAC TTG TTG GGC CCA CTT TAT GCA GCT TTG AAA ATG GAA AGT 720Ala Glu Tyr Leu Leu Gly Pro Leu Tyr Ala Ala Leu Lys Met Glu Ser225 230 235 240ATG GAA ATC ATT GAG GAG ATT CAA TGC CAA ACT CAA CAG GAA AAC CTC 768Met Glu Ile Ile Glu Glu Ile Gln Cys Gln Thr Gln Gln Glu Asn Leu245 250 255AGC AGT AAT AGT GAT GGA ATA TCA CCC AAA AGG CGT CGT CTC AGC TCG 816Ser Ser Asn Ser Asp Gly Ile Ser Pro Lys Arg Arg Arg Leu Ser Ser260 265 270TCT CTA AAC CCT TCT AAA AGA GCA CCA AAA CAG ACT GAG GAA ATT AAA 864Ser Leu Asn Pro Ser Lys Arg Ala Pro Lys Gln Thr Glu Glu Ile Lys275 280 285CAT GTG GAC ATG AAC CAA AAG AGC ATA TTA TGG AGT GCA CTG AAA CAG 912His Val Asp Met Asn Gln Lys Ser Ile Leu Trp Ser Ala Leu Lys Gln290 295 300AAA GCT GAA TCC CTT CAG ATT TCC CTT GAA TAC AGT GGC CTA AAG AAT 960Lys Ala Glu Ser Leu Gln Ile Ser Leu Glu Tyr Ser Gly Leu Lys Asn305 310 315 320CCT GTT ATT GAG ATG TTA GAA GGA ATT GCT GTT GTC TTA CAA CTG ACT 1008Pro Val Ile Glu Met Leu Glu Gly Ile Ala Val Val Leu Gln Leu Thr325 330 335GCT CTG TGT ACT GTT CAT TGT TCT CAT CAA AAC ATG AAC TGC CGT ACT 1056Ala Leu Cys Thr Val His Cys Ser His Gln Asn Met Asn Cys Arg Thr340 345 350TTC AAG GAC TGT CAA CAT AAA TCC AAG AAG AAA CCT TCT GTA GTG ATA 1104Phe Lys Asp Cys Gln His Lys Ser Lys Lys Lys Pro Ser Val Val Ile355 360 365ACT TGG ATG TCA TTG GAT TTT TAC ACA ACA GTG CTT AAG AGC TGT AGA 1152Thr Trp Met Ser Leu Asp Phe Tyr Thr Thr Val Leu Lys Ser Cys Arg370 375 380AGG TTG TTA GAA TCT GTT CAG AAA CGG ACT GGA GGC AAC ATT GAT AAG 1200Arg Leu Leu Glu Ser Val Gln Lys Arg Thr Gly Gly Asn Ile Asp Lys385 390 395 400GTG GTG AAA ATT TAT GAT GCT TTG ATT TAT ATG CAA GTA AAC AGT TCA 1248Val Val Lys Ile Tyr Asp Ala Leu Ile Tyr Met Gln Val Asn Ser Ser405 410 415TTT GAA GAT CAT ATC CTG GAA GAT TTA TGT GGA ATG CTC TCA CTT CCA 1296Phe Glu Asp His Ile Leu Glu Asp Leu Cys Gly Met Leu Ser Leu Pro420 425 430TGG ATT TAT TCC CAT TCT GAT GAT GGC TGT TTA AAG TTG ACC ACA TTT 1344Trp Ile Tyr Ser His Ser Asp Asp Gly Cys Leu Lys Leu Thr Thr Phe435 440 445GCC GCT AAT CTT CTA ACA TTA AGC TGT AGG ATT TCA GAT AGC TAT TCA 1392Ala Ala Asn Leu Leu Thr Leu Ser Cys Arg Ile Ser Asp Ser Tyr Ser450 455 460CCA CAG GCA CAA TCA CGA TGT GTG TTT CTT CTG ACT CTG TTT CCA AGA 1440Pro Gln Ala Gln Ser Arg Cys Val Phe Leu Leu Thr Leu Phe Pro Arg465 470 475 480AGA ATA TTC CTT GAG TGG AGA ACA GCA GTT TAC AAC TGG GCC CTG CAG 1488Arg Ile Phe Leu Glu Trp Arg Thr Ala Val Tyr Asn Trp Ala Leu Gln485 490 495AGC TCC CAT GAA GTA ATC CGG GCT AGT TGT GTT AGT GGA TTT TTT ATC 1536Ser Ser His Glu Val Ile Arg Ala Ser Cys Val Ser Gly Phe Phe Ile500 505 510TTA TTG CAG CAG CAG AAT TCT TGT AAC AGA GTT CCC AAG ATT CTT ATA 1584Leu Leu Gln Gln Gln Asn Ser Cys Asn Arg Val Pro Lys Ile Leu Ile515 520 525GAT AAA GTC AAA GAT GAT TCT GAC ATT GTC AAG AAA GAA TTT GCT TCT 1632Asp Lys Val Lys Asp Asp Ser Asp Ile Val Lys Lys Glu Phe Ala Ser530 535 540ATA CTT GGT CAA CTT GTC TGT ACT CTT CAC GGC ATG TTT TAT CTG ACA 1680Ile Leu Gly Gln Leu Val Cys Thr Leu His Gly Met Phe Tyr Leu Thr545 550 555 560AGT TCT TTA ACA GAA CCT TTC TCT GAA CAC GGA CAT GTG GAC CTC TTC 1728Ser Ser Leu Thr Glu Pro Phe Ser Glu His Gly His Val Asp Leu Phe565 570 575TGT AGG AAC TTG AAA GCC ACT TCT CAA CAT GAA TGT TCA TCT TCT CAA 1776Cys Arg Asn Leu Lys Ala Thr Ser Gln His Glu Cys Ser Ser Ser Gln580 585 590CTA AAA GCT TCT GTC TGC AAG CCA TTC CTT TTC CTA CTG AAA AAA AAA 1824Leu Lys Ala Ser Val Cys Lys Pro Phe Leu Phe Leu Leu Lys Lys Lys595 600 605ATA CCT AGT CCA GTA AAA CTT GCT TTC ATA GAT AAT CTA CAT CAT CTT 1872Ile Pro Ser Pro Val Lys Leu Ala Phe Ile Asp Asn Leu His His Leu610 615 620TGT AAG CAT CTT GAT TTT AGA GAA GAT GAA ACA GAT GTA AAA GCA GTT 1920Cys Lys His Leu Asp Phe Arg Glu Asp Glu Thr Asp Val Lys Ala Val625 630 635 640CTT GGA ACT TTA TTA AAT TTA ATG GAA GAT CCA GAC AAA GAT GTT AGA 1968Leu Gly Thr Leu Leu Asn Leu Met Glu Asp Pro Asp Lys Asp Val Arg645 650 655GTG GCT TTT AGT GGA AAT ATC AAG CAC ATA TTG GAA TCC TTG GAC TCT 2016Val Ala Phe Ser Gly Asn Ile Lys His Ile Leu Glu Ser Leu Asp Ser660 665 670GAA GAT GGA TTT ATA AAG GAG CTT TTT GTC TTA AGA ATG AAG GAA GCA 2064Glu Asp Gly Phe Ile Lys Glu Leu Phe Val Leu Arg Met Lys Glu Ala675 680 685TAT ACA CAT GCC CAA ATA TCA AGA AAT AAT GAG CTG AAG GAT ACC TTG 2112Tyr Thr His Ala Gln Ile Ser Arg Asn Asn Glu Leu Lys Asp Thr Leu690 695 700ATT CTT ACA ACA GGG GAT ATT GGA AGG GCC GCA AAA GGA GAT TTG GTA 2160Ile Leu Thr Thr Gly Asp Ile Gly Arg Ala Ala Lys Gly Asp Leu Val705 710 715 720CCA TTT GCA CTC TTA CAC TTA TTG CAT TGT TTG TTA TCC AAG TCA GCA 2208Pro Phe Ala Leu Leu His Leu Leu His Cys Leu Leu Ser Lys Ser Ala725 730 735TCT GTC TCT GGA GCA GCA TAC ACA GAA ATT AGA GCT CTG GTT GCA GCT 2256Ser Val Ser Gly Ala Ala Tyr Thr Glu Ile Arg Ala Leu Val Ala Ala740 745 750AAA AGT GTT AAA CTG CAA AGT TTT TTC AGC CAG TAT AAG AAA CCC ATC 2304Lys Ser Val Lys Leu Gln Ser Phe Phe Ser Gln Tyr Lys Lys Pro Ile755 760 765TGT CAG TTT TTG GTA GAA TCC CTT CAC TCT AGT CAG ATG ACA GCA CTT 2352Cys Gln Phe Leu Val Glu Ser Leu His Ser Ser Gln Met Thr Ala Leu770 775 780CCG AAT ACT CCA TGC CAG AAT GCT GAC GTG CGA AAA CAA GAT GTG GCT 2400Pro Asn Thr Pro Cys Gln Asn Ala Asp Val Arg Lys Gln Asp Val Ala785 790 795 800CAC CAG AGA GAA ATG GCT TTA AAT ACG TTG TCT GAA ATT GCC AAC GTT 2448His Gln Arg Glu Met Ala Leu Asn Thr Leu Ser Glu Ile Ala Asn Val805 810 815TTC GAC TTT CCT GAT CTT AAT CGT TTT CTT ACT AGG ACA TTA CAA GTT 2496Phe Asp Phe Pro Asp Leu Asn Arg Phe Leu Thr Arg Thr Leu Gln Val820 825 830CTA CTA CCT GAT CTT GCT GCC AAA GCA AGC CCT GCA GCT TCT GCT CTC 2544Leu Leu Pro Asp Leu Ala Ala Lys Ala Ser Pro Ala Ala Ser Ala Leu835 840 845ATT CGA ACT TTA GGA AAA CAA TTA AAT GTC AAT CGT AGA GAG ATT TTA 2592Ile Arg Thr Leu Gly Lys Gln Leu Asn Val Asn Arg Arg Glu Ile Leu850 855 860ATA AAC AAC TTC AAA TAT ATT TTT TCT CAT TTG GTC TGT TCT TGT TCC 2640Ile Asn Asn Phe Lys Tyr Ile Phe Ser His Leu Val Cys Ser Cys Ser865 870 875 880AAA GAT GAA TTA GAA CGT GCC CTT CAT TAT CTG AAG AAT GAA ACA GAA 2688Lys Asp Glu Leu Glu Arg Ala Leu His Tyr Leu Lys Asn Glu Thr Glu885 890 895ATT GAA CTG GGG AGC CTG TTG AGA CAA GAT TTC CAA GGA TTG CAT AAT 2736Ile Glu Leu Gly Ser Leu Leu Arg Gln Asp Phe Gln Gly Leu His Asn900 905 910GAA TTA TTG CTG CGT ATT GGA GAA CAC TAT CAA CAG GTT TTT AAT GGT 2784Glu Leu Leu Leu Arg Ile Gly Glu His Tyr Gln Gln Val Phe Asn Gly915 920 925TTG TCA ATA CTT GCC TCA TTT GCA TCC AGT GAT GAT CCA TAT CAG GGC 2832Leu Ser Ile Leu Ala Ser Phe Ala Ser Ser Asp Asp Pro Tyr Gln Gly930 935 940CCG AGA GAT ATC ATA TCA CCT GAA CTG ATG GCT GAT TAT TTA CAA CCC 2880Pro Arg Asp Ile Ile Ser Pro Glu Leu Met Ala Asp Tyr Leu Gln Pro945 950 955 960AAA TTG TTG GGC ATT TTG GCT TTT TTT AAC ATG CAG TTA CTG AGC TCT 2928Lys Leu Leu Gly Ile Leu Ala Phe Phe Asn Met Gln Leu Leu Ser Ser965 970 975AGT GTT GGC ATT GAA GAT AAG AAA ATG GCC TTG AAC AGT TTG ATG TCT 2976Ser Val Gly Ile Glu Asp Lys Lys Met Ala Leu Asn Ser Leu Met Ser980 985 990TTG ATG AAG TTA ATG GGA CCC AAA CAT GTC AGT TCT GTG AGG GTG AAG 3024Leu Met Lys Leu Met Gly Pro Lys His Val Ser Ser Val Arg Val Lys995 10001005ATG ATG ACC ACA CTG AGA ACT GGC CTT CGA TTC AAG GAT GAT TTT CCT 3072Met Met Thr Thr Leu Arg Thr Gly Leu Arg Phe Lys Asp Asp Phe Pro101010151020GAA TTG TGT TGC AGA GCT TGG GAC TGC TTT GTT CGC TGC CTG GAT CAT 3120Glu Leu Cys Cys Arg Ala Trp Asp Cys Phe Val Arg Cys Leu Asp His1025103010351040GCT TGT CTG GGC TCC CTT CTC AGT CAT GTA ATA GTA GCT TTG TTA CCT 3168Ala Cys Leu Gly Ser Leu Leu Ser His Val Ile Val Ala Leu Leu Pro104510501055CTT ATA CAC ATC CAG CCT AAA GAA ACT GCA GCT ATC TTC CAC TAC CTC 3216Leu Ile His Ile Gln Pro Lys Glu Thr Ala Ala Ile Phe His Tyr Leu106010651070ATA ATT GAA AAC AGG GAT GCT GTG CAA GAT TTT CTT CAT GAA ATA TAT 3264Ile Ile Glu Asn Arg Asp Ala Val Gln Asp Phe Leu His Glu Ile Tyr107510801085TTT TTA CCT GAT CAT CCA GAA TTA AAA AAG ATA AAA GCC GTT CTC CAG 3312Phe Leu Pro Asp His Pro Glu Leu Lys Lys Ile Lys Ala Val Leu Gln109010951100GAA TAC AGA AAG GAG ACC TCT GAG AGC ACT GAT CTT CAG ACA ACT CTT 3360Glu Tyr Arg Lys Glu Thr Ser Glu Ser Thr Asp Leu Gln Thr Thr Leu1105111011151120CAG CTC TCT ATG AAG GCC ATT CAA CAT GAA AAT GTC GAT GTT CGT ATT 3408Gln Leu Ser Met Lys Ala Ile Gln His Glu Asn Val Asp Val Arg Ile112511301135CAT GCT CTT ACA AGC TTG AAG GAA ACC TTG TAT AAA AAT CAG GAA AAA 3456His Ala Leu Thr Ser Leu Lys Glu Thr Leu Tyr Lys Asn Gln Glu Lys114011451150CTG ATA AAG TAT GCA ACA GAC AGT GAA ACA GTA GAA CCT ATT ATC TCA 3504Leu Ile Lys Tyr Ala Thr Asp Ser Glu Thr Val Glu Pro Ile Ile Ser115511601165CAG TTG GTG ACA GTG CTT TTG AAA GGT TGC CAA GAT GCA AAC TCT CAA 3552Gln Leu Val Thr Val Leu Leu Lys Gly Cys Gln Asp Ala Asn Ser Gln117011751180GCT CGG TTG CTC TGT GGG GAA TGT TTA GGG GAA TTG GGG GCG ATA GAT 3600Ala Arg Leu Leu Cys Gly Glu Cys Leu Gly Glu Leu Gly Ala Ile Asp1185119011951200CCA GGT CGA TTA GAT TTC TCA ACA ACT GAA ACT CAA GGA AAA GAT TTT 3648Pro Gly Arg Leu Asp Phe Ser Thr Thr Glu Thr Gln Gly Lys Asp Phe120512101215ACA TTT GTG ACT GGA GTA GAA GAT TCA AGC TTT GCC TAT GGA TTA TTG 3696Thr Phe Val Thr Gly Val Glu Asp Ser Ser Phe Ala Tyr Gly Leu Leu122012251230ATG GAG CTA ACA AGA GCT TAC CTT GCG TAT GCT GAT AAT AGC CGA GCT 3744Met Glu Leu Thr Arg Ala Tyr Leu Ala Tyr Ala Asp Asn Ser Arg Ala123512401245CCA GAT TCA GCT GCC TAT GCC ATT CAG GAG TTG CTT TCT ATT TAT GAC 3792Pro Asp Ser Ala Ala Tyr Ala Ile Gln Glu Leu Leu Ser Ile Tyr Asp125012551260TGT AGA GAG ATG GAG ACC AAC GGC CCA GGT CAC CAA TTG TGG AGG AGA 3840Cys Arg Glu Met Glu Thr Asn Gly Pro Gly His Gln Leu Trp Arg Arg1265127012751280TTT CCT GAG CAT GTT CGG GAA ATA CTA GAA CCT CAT CTA AAT ACC AGA 3888Phe Pro Glu His Val Arg Glu Ile Leu Glu Pro His Leu Asn Thr Arg128512901295TAC AAG AGT TCT CAG AAG TCA ACC GAT TGG TCT GGA GTA AAG AAG CCA 3936Tyr Lys Ser Ser Gln Lys Ser Thr Asp Trp Ser Gly Val Lys Lys Pro130013051310ATT TAC TTA AGT AAA TTG GGT AGT AAC TTT GCA GAA TGG TCA GCA TCT 3984Ile Tyr Leu Ser Lys Leu Gly Ser Asn Phe Ala Glu Trp Ser Ala Ser131513201325TGG GCA GGT TAT CTT ATT ACA AAG GTT CGA CAT GAT CTT GCC AGT AAA 4032Trp Ala Gly Tyr Leu Ile Thr Lys Val Arg His Asp Leu Ala Ser Lys133013351340ATT TTC ACC TGC TGT AGC ATT ATG ATG AAG CAT GAT TTC AAA GTG ACC 4080Ile Phe Thr Cys Cys Ser Ile Met Met Lys His Asp Phe Lys Val Thr1345135013551360ATC TAT CTT CTT CCA CAT ATT CTG GTG TAT GTC TTA CTG GGT TGT AAT 4128Ile Tyr Leu Leu Pro His Ile Leu Val Tyr Val Leu Leu Gly Cys Asn136513701375CAA GAA GAT CAG CAG GAG GTT TAT GCA GAA ATT ATG GCA GTT CTA AAG 4176Gln Glu Asp Gln Gln Glu Val Tyr Ala Glu Ile Met Ala Val Leu Lys138013851390CAT GAC GAT CAG CAT ACC ATA AAT ACC CAA GAC ATT GCA TCT GAT CTG 4224His Asp Asp Gln His Thr Ile Asn Thr Gln Asp Ile Ala Ser Asp Leu139514001405TGT CAA CTC AGT ACA CAG ACT GTG TTC TCC ATG CTT GAC CAT CTC ACA 4272Cys Gln Leu Ser Thr Gln Thr Val Phe Ser Met Leu Asp His Leu Thr141014151420CAG TGG GCA AGG CAC AAA TTT CAG GCA CTG AAA GCT GAG AAA TGT CCA 4320Gln Trp Ala Arg His Lys Phe Gln Ala Leu Lys Ala Glu Lys Cys Pro1425143014351440CAC AGC AAA TCA AAC AGA AAT AAG GTA GAC TCA ATG GTA TCT ACT GTG 4368His Ser Lys Ser Asn Arg Asn Lys Val Asp Ser Met Val Ser Thr Val144514501455GAT TAT GAA GAC TAT CAG AGT GTA ACC CGT TTT CTA GAC CTC ATA CCC 4416Asp Tyr Glu Asp Tyr Gln Ser Val Thr Arg Phe Leu Asp Leu Ile Pro146014651470CAG GAT ACT CTG GCA GTA GCT TCC TTT CGC TCC AAA GCA TAC ACA CGA 4464Gln Asp Thr Leu Ala Val Ala Ser Phe Arg Ser Lys Ala Tyr Thr Arg147514801485GCT GTA ATG CAC TTT GAA TCA TTT ATT ACA GAA AAG AAG CAA AAT ATT 4512Ala Val Met His Phe Glu Ser Phe Ile Thr Glu Lys Lys Gln Asn Ile149014951500CAG GAA CAT CTT GGA TTT TTA CAG AAA TTG TAT GCT GCT ATG CAT GAA 4560Gln Glu His Leu Gly Phe Leu Gln Lys Leu Tyr Ala Ala Met His Glu1505151015151520CCT GAT GGA GTG TCC GGA GTC AGT GCA ATT AGA AAG GCA GAA CCA TCT 4608Pro Asp Gly Val Ser Gly Val Ser Ala Ile Arg Lys Ala Glu Pro Ser152515301535CTA AAA GAA CAG ATC CTT GAA CAT GAA AGC CTT GGC TTG CTG AGG GAT 4656Leu Lys Glu Gln Ile Leu Glu His Glu Ser Leu Gly Leu Leu Arg Asp154015451550GCC ACT GCT TGT TAT GAC AGG GCT ATT CAG CTA GAA CCA GAC CAG ATC 4704Ala Thr Ala Cys Tyr Asp Arg Ala Ile Gln Leu Glu Pro Asp Gln Ile155515601565ATT CAT TAC CAT GGT GTA GTA AAG TCC ATG TTA GGT CTT GGT CAG CTG 4752Ile His Tyr His Gly Val Val Lys Ser Met Leu Gly Leu Gly Gln Leu157015751580TCT ACT GTT ATC ACT CAG GTG AAT GGA GTG CAT GCT AAC AGG TCC GAG 4800Ser Thr Val Ile Thr Gln Val Asn Gly Val His Ala Asn Arg Ser Glu1585159015951600TGG ACA GAT GAA TTA AAC ACG TAC AGA GTG GAA GCA GCT TGG AAA TTG 4848Trp Thr Asp Glu Leu Asn Thr Tyr Arg Val Glu Ala Ala Trp Lys Leu160516101615TCA CAG TGG GAT TTG GTG GAA AAC TAT TTG GCA GCA GAT GGA AAA TCT 4896Ser Gln Trp Asp Leu Val Glu Asn Tyr Leu Ala Ala Asp Gly Lys Ser162016251630ACA ACA TGG AGT GTC AGA CTG GGA CAG CTA TTA TTA TCA GCC AAA AAA 4944Thr Thr Trp Ser Val Arg Leu Gly Gln Leu Leu Leu Ser Ala Lys Lys163516401645AGA GAT ATC ACA GCT TTT TAT GAC TCA CTG AAA CTA GTG AGA GCA GAA 4992Arg Asp Ile Thr Ala Phe Tyr Asp Ser Leu Lys Leu Val Arg Ala Glu165016551660CAA ATT GTA CCT CTT TCA GCT GCA AGC TTT GAA AGA GGC TCC TAC CAA 5040Gln Ile Val Pro Leu Ser Ala Ala Ser Phe Glu Arg Gly Ser Tyr Gln1665167016751680CGA GGA TAT GAA TAT ATT GTG AGA TTG CAC ATG TTA TGT GAG TTG GAG 5088Arg Gly Tyr Glu Tyr Ile Val Arg Leu His Met Leu Cys Glu Leu Glu168516901695CAT AGC ATC AAA CCA CTT TTC CAG CAT TCT CCA GGT GAC AGT TCT CAA 5136His Ser Ile Lys Pro Leu Phe Gln His Ser Pro Gly Asp Ser Ser Gln170017051710GAA GAT TCT CTA AAC TGG GTA GCT CGA CTA GAA ATG ACC CAG AAT TCC 5184Glu Asp Ser Leu Asn Trp Val Ala Arg Leu Glu Met Thr Gln Asn Ser171517201725TAC AGA GCC AAG GAG CCT ATC CTG GCT CTC CGG AGG GCT TTA CTA AGC 5232Tyr Arg Ala Lys Glu Pro Ile Leu Ala Leu Arg Arg Ala Leu Leu Ser173017351740CTC AAC AAA AGA CCA GAT TAC AAT GAA ATG GTT GGA GAA TGC TGG CTG 5280Leu Asn Lys Arg Pro Asp Tyr Asn Glu Met Val Gly Glu Cys Trp Leu1745175017551760CAG AGT GCC AGG GTA GCT AGA AAG GCT GGT CAC CAC CAG ACA GCC TAC 5328Gln Ser Ala Arg Val Ala Arg Lys Ala Gly His His Gln Thr Ala Tyr176517701775AAT GCT CTC CTT AAT GCA GGG GAA TCA CGA CTC GCT GAA CTG TAC GTG 5376Asn Ala Leu Leu Asn Ala Gly Glu Ser Arg Leu Ala Glu Leu Tyr Val178017851790GAA AGG GCA AAG TGG CTC TGG TCC AAG GGT GAT GTT CAC CAG GCA CTA 5424Glu Arg Ala Lys Trp Leu Trp Ser Lys Gly Asp Val His Gln Ala Leu179518001805ATT GTT CTT CAA AAA GGT GTT GAA TTA TGT TTT CCT GAA AAT GAA ACC 5472Ile Val Leu Gln Lys Gly Val Glu Leu Cys Phe Pro Glu Asn Glu Thr181018151820CCA CCT GAG GGT AAG AAC ATG TTA ATC CAT GGT CGA GCT ATG CTA CTA 5520Pro Pro Glu Gly Lys Asn Met Leu Ile His Gly Arg Ala Met Leu Leu1825183018351840GTG GGC CGA TTT ATG GAA GAA ACA GCT AAC TTT GAA AGC AAT GCA ATT 5568Val Gly Arg Phe Met Glu Glu Thr Ala Asn Phe Glu Ser Asn Ala Ile184518501855ATG AAA AAA TAT AAG GAT GTG ACC GCG TGC CTG CCA GAA TGG GAG GAT 5616Met Lys Lys Tyr Lys Asp Val Thr Ala Cys Leu Pro Glu Trp Glu Asp186018651870GGG CAT TTT TAC CTT GCC AAG TAC TAT GAC AAA TTG ATG CCC ATG GTC 5664Gly His Phe Tyr Leu Ala Lys Tyr Tyr Asp Lys Leu Met Pro Met Val187518801885ACA GAC AAC AAA ATG GAA AAG CAA GGT GAT CTC ATC CGG TAT ATA GTT 5712Thr Asp Asn Lys Met Glu Lys Gln Gly Asp Leu Ile Arg Tyr Ile Val189018951900CTT CAT TTT GGC AGA TCT CTA CAA TAT GGA AAT CAG TTC ATA TAT CAG 5760Leu His Phe Gly Arg Ser Leu Gln Tyr Gly Asn Gln Phe Ile Tyr Gln1905191019151920TCA ATG CCA CGA ATG TTA ACT CTA TGG CTT GAT TAT GGT ACA AAG GCA 5808Ser Met Pro Arg Met Leu Thr Leu Trp Leu Asp Tyr Gly Thr Lys Ala192519301935TAT GAA TGG GAA AAA GCT GGC CGC TCC GAT CGT GTA CAA ATG AGG AAT 5856Tyr Glu Trp Glu Lys Ala Gly Arg Ser Asp Arg Val Gln Met Arg Asn194019451950GAT TTG GGT AAA ATA AAC AAG GTT ATC ACA GAG CAT ACA AAC TAT TTA 5904Asp Leu Gly Lys Ile Asn Lys Val Ile Thr Glu His Thr Asn Tyr Leu195519601965GCT CCA TAT CAA TTT TTG ACT GCT TTT TCA CAA TTG ATC TCT CGA ATT 5952Ala Pro Tyr Gln Phe Leu Thr Ala Phe Ser Gln Leu Ile Ser Arg Ile197019751980TGT CAT TCT CAC GAT GAA GTT TTT GTT GTG CTT GAT GGA AAT AAT AGC 6000Cys His Ser His Asp Glu Val Phe Val Val Leu Asp Gly Asn Asn Ser1985199019952000CAA GTA TTT CTA GCC TAT CCT CAA CAA GCA ATG TGG ATG ATG ACA GCT 6048Gln Val Phe Leu Ala Tyr Pro Gln Gln Ala Met Trp Met Met Thr Ala200520102015GTG TCA AAG TCA TCT TAT CCC ATG CGT GTG AAC AGA TGC AAG GAA ATC 6096Val Ser Lys Ser Ser Tyr Pro Met Arg Val Asn Arg Cys Lys Glu Ile202020252030CTC AAT AAA GCT ATT CAT ATG AAA AAA TCC TTA GAG AAG TTT GTT GGA 6144Leu Asn Lys Ala Ile His Met Lys Lys Ser Leu Glu Lys Phe Val Gly203520402045GAT GCA ACT CGC CTA ACA GAT AAG CTT CTA GAA TTG TGC AAT AAA CCG 6192Asp Ala Thr Arg Leu Thr Asp Lys Leu Leu Glu Leu Cys Asn Lys Pro205020552060GTT GAT GGA AGT AGT TCC ACA TTA AGC ATG AGC ACT CAT TTT AAA ATG 6240Val Asp Gly Ser Ser Ser Thr Leu Ser Met Ser Thr His Phe Lys Met2065207020752080CTT AAA AAG CTG GTA GAA GAA GCA ACA TTT AGT GAA ATC CTC ATT CCT 6288Leu Lys Lys Leu Val Glu Glu Ala Thr Phe Ser Glu Ile Leu Ile Pro208520902095CTA CAA TCA GTC ATG ATA CCT ACA CTT CCA TCA ATT CTG GGT ACC CAT 6336Leu Gln Ser Val Met Ile Pro Thr Leu Pro Ser Ile Leu Gly Thr His210021052110GCT AAC CAT GCT AGC CAT GAA CCA TTT CCT GGA CAT TGG GCC TAT ATT 6384Ala Asn His Ala Ser His Glu Pro Phe Pro Gly His Trp Ala Tyr Ile211521202125GCA GGG TTT GAT GAT ATG GTG GAA ATT CTT GCT TCT CTT CAG AAA CCA 6432Ala Gly Phe Asp Asp Met Val Glu Ile Leu Ala Ser Leu Gln Lys Pro213021352140AAG AAG ATT TCT TTA AAA GGC TCA GAT GGA AAG TTC TAC ATC ATG ATG 6480Lys Lys Ile Ser Leu Lys Gly Ser Asp Gly Lys Phe Tyr Ile Met Met2145215021552160TGT AAG CCA AAA GAT GAC CTG AGA AAG GAT TGT AGA CTA ATG GAA TTC 6528Cys Lys Pro Lys Asp Asp Leu Arg Lys Asp Cys Arg Leu Met Glu Phe216521702175AAT TCC TTG ATT AAT AAG TGC TTA AGA AAA GAT GCA GAG TCT CGT AGA 6576Asn Ser Leu Ile Asn Lys Cys Leu Arg Lys Asp Ala Glu Ser Arg Arg218021852190AGA GAA CTT CAT ATT CGA ACA TAT GCA GTT ATT CCA CTA AAT GAT GAA 6624Arg Glu Leu His Ile Arg Thr Tyr Ala Val Ile Pro Leu Asn Asp Glu219522002205TGT GGG ATT ATT GAA TGG GTG AAC AAC ACT GCT GGT TTG AGA CCT ATT 6672Cys Gly Ile Ile Glu Trp Val Asn Asn Thr Ala Gly Leu Arg Pro Ile221022152220CTG ACC AAA CTA TAT AAA GAA AAG GGA GTG TAT ATG ACA GGA AAA GAA 6720Leu Thr Lys Leu Tyr Lys Glu Lys Gly Val Tyr Met Thr Gly Lys Glu2225223022352240CTT CGC CAG TGT ATG CTA CCA AAG TCA GCA GCT TTA TCT GAA AAA CTC 6768Leu Arg Gln Cys Met Leu Pro Lys Ser Ala Ala Leu Ser Glu Lys Leu224522502255AAA GTA TTC CGA GAA TTT CTC CTG CCC AGG CAT CCT CCT ATT TTT CAT 6816Lys Val Phe Arg Glu Phe Leu Leu Pro Arg His Pro Pro Ile Phe His226022652270GAG TGG TTT CTG AGA ACA TTC CCT GAT CCT ACA TCA TGG TAC AGT AGT 6864Glu Trp Phe Leu Arg Thr Phe Pro Asp Pro Thr Ser Trp Tyr Ser Ser227522802285AGA TCA GCT TAC TGC CGT TCC ACT GCA GTA ATG TCA ATG GTT GGT TAT 6912Arg Ser Ala Tyr Cys Arg Ser Thr Ala Val Met Ser Met Val Gly Tyr229022952300ATT CTG GGG CTT GGA GAC CGT CAT GGT GAA AAT ATT CTC TTT GAT TCT 6960Ile Leu Gly Leu Gly Asp Arg His Gly Glu Asn Ile Leu Phe Asp Ser2305231023152320TTG ACT GGT GAA TGC GTA CAT GTA GAT TTC AAT TGT CTT TTC AAT AAG 7005Leu Thr Gly Glu Cys Val His Val Asp Phe Asn Cys Leu Phe Asn Lys232523302335GGA GAA ACC TTT GAA GTT CCA GAA ATT GTG CCA TTT CGC CTG ACT CAT 7056Gly Glu Thr Phe Glu Val Pro Glu Ile Val Pro Phe Arg Leu Thr His234023452350AAT ATG GTT AAT GGA ATG GGT CCT ATG GGA ACA GAG GGT CTT TTT CGA 7204Asn Met Val Asn Gly Met Gly Pro Met Gly Thr Glu Gly Leu Phe Arg235523602365AGA GCA TGT GAA GTT ACA ATG AGG CTG ATG CGT GAT CAG CGA GAG CCT 7152Arg Ala Cys Glu Val Thr Met Arg Leu Met Arg Asp Gln Arg Glu Pro237023752380TTA ATG AGT GTC TTA AAG ACT TTT CTA CAT GAT CCT CTT GTG GAA TGG 7200Leu Met Ser Val Leu Lys Thr Phe Leu His Asp Pro Leu Val Glu Trp2385239023952400AGT AAA CCA GTG AAA GGG CAT TCC AAA GCG CCA CTG AAT GAA ACT GGA 7248Ser Lys Pro Val Lys Gly His Ser Lys Ala Pro Leu Asn Glu Thr Gly240524102415GAA GTT GTC AAT GAA AAG GCC AAG ACC CAT GTT CTT GAC ATT GAG CAG 7296Glu Val Val Asn Glu Lys Ala Lys Thr His Val Leu Asp Ile Glu Gln242024252430CGA CTA CAA GGT GTA ATC AAG ACT CGA AAT AGA GTG ACA GGA CTG CCG 7344Arg Leu Gln Gly Val Ile Lys Thr Arg Asn Arg Val Thr Gly Leu Pro243524402445TTA TCT ATT GAA GGA CAT GTG CAT TAC CTT ATA CAA GAA GCT ACT GAT 7392Leu Ser Ile Glu Gly His Val His Tyr Leu Ile Gln Glu Ala Thr Asp245024552460GAA AAC TTA CTA TGC CAG ATG TAT CTT GGT TGG ACT CCA TAT ATG 7437Glu Asn Leu Leu Cys Gln Met Tyr Leu Gly Trp Thr Pro Tyr Met246524702475TGA 7440(2)SEQ ID NO18的说明(i)序列特征(A)长度2479个氨基酸(B)类型氨基酸(D)拓扑结构线性(ii)分子类型蛋白(xi)序列描述SEQ ID NO18Met Gly His Ala Val Glu Trp Pro Val Val Met Ser Arg Phe Leu Ser1 5 10 15Gln Leu Asp Glu His Met Gly Tyr Leu Gln Ser Ala Pro Leu Gln Leu20 25 30Met Ser Met Gln Lys Leu Glu Phe Ile Glu Val Thr Leu Leu Thr Val35 40 45Leu Thr Arg Ile Ile Ala Ile Val Phe Phe Arg Arg Gln Glu Leu Leu50 55 60Leu Trp Gln Ile Gly Cys Val Leu Leu Glu Tyr Gly Ser Pro Lys Ile65 70 75 80Lys Ser Leu Ala Ile Ser Phe Leu Thr Glu Leu Phe Gln Leu Gly Gly85 90 95Leu Pro Ala Gln Pro Ala Ser Thr Phe Phe Ser Ser Phe Leu Glu Leu100 105 110Leu Lys His Leu Val Glu Met Asp Thr Asp Gln Leu Lys Leu Tyr Glu115 120 125Glu Pro Leu Ser Lys Leu Ile Lys Thr Leu Phe Pro Phe Glu Ala Glu130 135 140Ala Tyr Arg Asn Ile Glu Pro Val Tyr Leu Asn Met Leu Leu Glu Lys145 150 155 160Leu Cys Val Met Phe Glu Asp Gly Val Leu Met Arg Leu Lys Ser Asp165 170 175Leu Leu Lys Ala Ala Leu Cys His Leu Leu Gln Tyr Phe Leu Lys Phe180 185 190Val Pro Ala Gly Tyr Glu Ser Ala Leu Gln Val Arg Lys Val Tyr Val195 200 205Arg Asn Ile Cys Lys Ala Leu Leu Asp Val Leu Gly Ile Glu Val Asp210 215 220Ala Glu Tyr Leu Leu Gly Pro Leu Tyr Ala Ala Leu Lys Met Glu Ser225 230 235 240Met Glu Ile Ile Glu Glu Ile Gln Cys Gln Thr Gln Gln Glu Asn Leu245 250 255Ser Ser Asn Ser Asp Gly Ile Ser Pro Lys Arg Arg Arg Leu Ser Ser260 265 270Ser Leu Asn Pro Ser Lys Arg Ala Pro Lys Gln Thr Glu Glu Ile Lys275 280 285His Val Asp Met Asn Gln Lys Ser Ile Leu Trp Ser Ala Leu Lys Gln290 295 300Lys Ala Glu Ser Leu Gln Ile Ser Leu Glu Tyr Ser Gly Leu Lys Asn305 310 315 320Pro Val Ile Glu Met Leu Glu Gly Ile Ala Val Val Leu Gln Leu Thr325 330 335Ala Leu Cys Thr Val His Cys Ser His Gln Asn Met Asn Cys Arg Thr340 345 350Phe Lys Asp Cys Gln His Lys Ser Lys Lys Lys Pro Ser Val Val Ile355 360 365Thr Trp Met Ser Leu Asp Phe Tyr Thr Thr Val Leu Lys Ser Cys Arg370 375 380Arg Leu Leu Glu Ser Val Gln Lys Arg Thr Gly Gly Asn Ile Asp Lys385 390 395 400Val Val Lys Ile Tyr Asp Ala Leu Ile Tyr Met Gln Val Asn Ser Ser405 410 415Phe Glu Asp His Ile Leu Glu Asp Leu Cys Gly Met Leu Ser Leu Pro420 425 430Trp Ile Tyr Ser His Ser Asp Asp Gly Cys Leu Lys Leu Thr Thr Phe435 440 445Ala Ala Asn Leu Leu Thr Leu Sar Cys Arg Ile Ser Asp Ser Tyr Ser450 455 460Pro Gln Ala Gln Ser Arg Cys Val Phe Leu Leu Thr Leu Phe Pro Arg465 470 475 480Arg Ile Phe Leu Glu Trp Arg Thr Ala Val Tyr Asn Trp Ala Leu Gln485 490 495Ser Ser His Glu Val Ile Arg Ala Ser Cys Val Ser Gly Phe Phe Ile500 505 510Leu Leu Gln Gln Gln Asn Ser Cys Asn Arg Val Pro Lys Ile Leu Ile515 520 525Asp Lys Val Lys Asp Asp Ser Asp Ile Val Lys Lys Glu Phe Ala Ser530 535 540Ile Leu Gly Gln Leu Val Cys Thr Leu His Gly Met Phe Tyr Leu Thr545 550 555 560Ser Ser Leu Thr Glu Pro Phe Ser Glu His Gly His Val Asp Leu Phe565 570 575Cys Arg Asn Leu Lys Ala Thr Ser Gln His Glu Cys Ser Ser Ser Gln580 585 590Leu Lys Ala Ser Val Cys Lys Pro Phe Leu Phe Leu Leu Lys Lys Lys595 600 605Ile Pro Ser Pro Val Lys Leu Ala Phe Ile Asp Asn Leu His His Leu610 615 620Cys Lys His Leu Asp Phe Arg Glu Asp Glu Thr Asp Val Lys Ala Val625 630 635 640Leu Gly Thr Leu Leu Asn Leu Met Glu Asp Pro Asp Lys Asp Val Arg645 650 655Val Ala Phe Ser Gly Asn Ile Lys His Ile Leu Glu Ser Leu Asp Ser660 665 670Glu Asp Gly Phe Ile Lys Glu Leu Phe Val Leu Arg Met Lys Glu Ala675 680 685Tyr Thr His Ala Gln Ile Ser Arg Asn Asn Glu Leu Lys Asp Thr Leu690 695 700Ile Leu Thr Thr Gly Asp Ile Gly Arg Ala Ala Lys Gly Asp Leu Val705 710 715 720Pro Phe Ala Leu Leu His Leu Leu His Cys Leu Leu Ser Lys Ser Ala725 730 735Ser Val Ser Gly Ala Ala Tyr Thr Glu Ile Arg Ala Leu Val Ala Ala740 745 750Lys Ser Val Lys Leu Gln Ser Phe Phe Ser Gln Tyr Lys Lys Pro Ile755 760 765Cys Gln Phe Leu Val Glu Ser Leu His Ser Ser Gln Met Thr Ala Leu770 775 780Pro Asn Thr Pro Cys Gln Asn Ala Asp Val Arg Lys Gln Asp Val Ala785 790 795 800His Gln Arg Glu Met Ala Leu Asn Thr Leu Ser Glu Ile Ala Asn Val805 810 815Phe Asp Phe Pro Asp Leu Asn Arg Phe Leu Thr Arg Thr Leu Gln Val820 825 830Leu Leu Pro Asp Leu Ala Ala Lys Ala Ser Pro Ala Ala Ser Ala Leu835 840 845Ile Arg Thr Leu Gly Lys Gln Leu Asn Val Asn Arg Arg Glu Ile Leu850 855 860Ile Asn Asn Phe Lys Tyr Ile Phe Ser His Leu Val Cys Ser Cys Ser865 870 875 880Lys Asp Glu Leu Glu Arg Ala Leu His Tyr Leu Lys Asn Glu Thr Glu885 890 895Ile Glu Leu Gly Ser Leu Leu Arg Gln Asp Phe Gln Gly Leu His Asn900 905 910Glu Leu Leu Leu Arg Ile Gly Glu His Tyr Gln Gln Val Phe Asn Gly915 920 925Leu Ser Ile Leu Ala Ser Phe Ala Ser Ser Asp Asp Pro Tyr Gln Gly930 935 940Pro Arg Asp Ile Ile Ser Pro Glu Leu Met Ala Asp Tyr Leu Gln Pro945 950 955 960Lys Leu Leu Gly Ile Leu Ala Phe Phe Asn Met Gln Leu Leu Ser Ser965 970 975Ser Val Gly Ile Glu Asp Lys Lys Met Ala Leu Asn Ser Leu Met Ser980 985 990Leu Met Lys Leu Met Gly Pro Lys His Val Ser Ser Val Arg Val Lys995 10001005Met Met Thr Thr Leu Arg Thr Gly Leu Arg Phe Lys Asp Asp Phe Pro101010151020Glu Leu Cys Cys Arg Ala Trp Asp Cys Phe Val Arg Cys Leu Asp His1025103010351040Ala Cys Leu Gly Ser Leu Leu Ser His Val Ile Val Ala Leu Leu Pro104510501055Leu Ile His Ile Gln Pro Lys Glu Thr Ala Ala Ile Phe His Tyr Leu106010651070Ile Ile Glu Asn Arg Asp Ala Val Gln Asp Phe Leu His Glu Ile Tyr107510801085Phe Leu Pro Asp His Pro Glu Leu Lys Lys Ile Lys Ala Val Leu Gln109010951100Glu Tyr Arg Lys Glu Thr Ser Glu Ser Thr Asp Leu Gln Thr Thr Leu1105111011151120Gln Leu Ser Met Lys Ala Ile Gln His Glu Asn Val Asp Val Arg Ile112511301135His Ala Leu Thr Ser Leu Lys Glu Thr Leu Tyr Lys Asn Gln Glu Lys114011451150Leu Ile Lys Tyr Ala Thr Asp Ser Glu Thr Val Glu Pro Ile Ile Ser115511601165Gln Leu Val Thr Val Leu Leu Lys Gly Cys Gln Asp Ala Asn Ser Gln117011751180Ala Arg Leu Leu Cys Gly Glu Cys Leu Gly Glu Leu Gly Ala Ile Asp1185119011951200Pro Gly Arg Leu Asp Phe Ser Thr Thr Glu Thr Gln Gly Lys Asp Phe120512101215Thr Phe Val Thr Gly Val Glu Asp Ser Ser Phe Ala Tyr Gly Leu Leu122012251230Met Glu Leu Thr Arg Ala Tyr Leu Ala Tyr Ala Asp Asn Ser Arg Ala123512401245Pro Asp Ser Ala Ala Tyr Ala Ile Gln Glu Leu Leu Ser Ile Tyr Asp125012551260Cys Arg Glu Met Glu Thr Asn Gly Pro Gly His Gln Leu Trp Arg Arg1265127012751280Phe Pro Glu His Val Arg Glu Ile Leu Glu Pro His Leu Asn Thr Arg128512901295Tyr Lys Ser Ser Gln Lys Ser Thr Asp Trp Ser Gly Val Lys Lys Pro130013051310Ile Tyr Leu Ser Lys Leu Gly Ser Asn Phe Ala Glu Trp Ser Ala Ser131513201325Trp Ala Gly Tyr Leu Ile Thr Lys Val Arg His Asp Leu Ala Ser Lys133013351340Ile Phe Thr Cys Cys Ser Ile Met Met Lys His Asp Phe Lys Val Thr1345135013551360Ile Tyr Leu Leu Pro His Ile Leu Val Tyr Val Leu Leu Gly Cys Asn136513701375Gln Glu Asp Gln Gln Glu Val Tyr Ala Glu Ile Met Ala Val Leu Lys138013851390His Asp Asp Gln His Thr Ile Asn Thr Gln Asp Ile Ala Ser Asp Leu139514001405Cys Gln Leu Ser Thr Gln Thr Val Phe Ser Met Leu Asp His Leu Thr141014151420Gln Trp Ala Arg His Lys Phe Gln Ala Leu Lys Ala Glu Lys Cys Pro1425143014351440His Ser Lys Ser Asn Arg Asn Lys Val Asp Ser Met Val Ser Thr Val144514501455Asp Tyr Glu Asp Tyr Gln Ser Val Thr Arg Phe Leu Asp Leu Ile Pro146014651470Gln Asp Thr Leu Ala Val Ala Ser Phe Arg Ser Lys Ala Tyr Thr Arg147514801485Ala Val Met His Phe Glu Ser Phe Ile Thr Glu Lys Lys Gln Asn Ile149014951500Gln Glu His Leu Gly Phe Leu Gln Lys Leu Tyr Ala Ala Met His Glu150515101515l520Pro Asp Gly Val Ser Gly Val Ser Ala Ile Arg Lys Ala Glu Pro Ser152515301535Leu Lys Glu Gln Ile Leu Glu His Glu Ser Leu Gly Leu Leu Arg Asp154015451550Ala Thr Ala Cys Tyr Asp Arg Ala Ile Gln Leu Glu Pro Asp Gln Ile155515601565Ile His Tyr His Gly Val Val Lys Ser Met Leu Gly Leu Gly Gln Leu157015751580Ser Thr Val Ile Thr Gln Val Asn Gly Val His Ala Asn Arg Ser Glu1585159015951600Trp Thr Asp Glu Leu Asn Thr Tyr Arg Val Glu Ala Ala Trp Lys Leu160516101615Ser Gln Trp Asp Leu Val Glu Asn Tyr Leu Ala Ala Asp Gly Lys Ser162016251630Thr Thr Trp Ser Val Arg Leu Gly Gln Leu Leu Leu Ser Ala Lys Lys163516401645Arg Asp Ile Thr Ala Phe Tyr Asp Ser Leu Lys Leu Val Arg Ala Glu165016551660Gln Ile Val Pro Leu Ser Ala Ala Ser Phe Glu Arg Gly Ser Tyr Gln1665167016751680Arg Gly Tyr Glu Tyr Ile Val Arg Leu His Met Leu Cys Glu Leu Glu168516901695His Ser Ile Lys Pro Leu Phe Gln His Ser Pro Gly Asp Ser Ser Gln170017051710Glu Asp Ser Leu Asn Trp Val Ala Arg Leu Glu Met Thr Gln Asn Ser171517201725Tyr Arg Ala Lys Glu Pro Ile Leu Ala Leu Arg Arg Ala Leu Leu Ser173017351740Leu Asn Lys Arg Pro Asp Tyr Asn Glu Met Val Gly Glu Cys Trp Leu1745175017551760Gln Ser Ala Arg Val Ala Arg Lys Ala Gly His His Gln Thr Ala TTr176517701775Asn Ala Leu Leu Asn Ala Gly Glu Ser Arg Leu Ala Glu Leu Tyr Val178017851790Glu Arg Ala Lys Trp Leu Trp Ser Lys Gly Asp Val His Gln Ala Leu179518001805Ile Val Leu Gln Lys Gly Val Glu Leu Cys Phe Pro Glu Asn Glu Thr181018151820Pro Pro Glu Gly Lys Asn Met Leu Ile His Gly Arg Ala Met Leu Leu1825183018351640Val Gly Arg Phe Met Glu Glu Thr Ala Asn Phe Glu Ser Asn Ala Ile184518501855Met Lys Lys Tyr Lys Asp Val Thr Ala Cys Leu Pro Glu Trp Glu Asp186018651870Gly His Phe Tyr Leu Ala Lys Tyr Tyr Asp Lys Leu Met Pro Met Val187518801885Thr Asp Asn Lys Met Glu Lys Gln Gly Asp Leu Ile Arg Tyr Ile Val189018951900Leu His Phe Gly Arg Ser Leu Gln Tyr Gly Asn Gln Phe Ile Tyr Gln1905191019151920Ser Met Pro Arg Met Leu Thr Leu Trp Leu Asp Tyr Gly Thr Lys Ala192519301935Tyr Glu Trp Glu Lys Ala Gly Arg Ser Asp Arg Val Gln Met Arg Asn194019451950Asp Leu Gly Lys Ile Asn Lys Val Ile Thr Glu His Thr Asn Tyr Leu195519601965Ala Pro Tyr Gln Phe Leu Thr Ala Phe Ser Gln Leu Ile Ser Arg Ile197019751980Cys His Ser His Asp Glu Val Phe Val Val Leu Asp Gly Asn Asn Ser1985199019952000Gln Val Phe Leu Ala Tyr Pro Gln Gln Ala Met Trp Met Met Thr Ala200520102015Val Ser Lys Ser Ser Tyr Pro Met Arg Val Asn Arg Cys Lys Glu Ile202020252030Leu Asn Lys Ala Ile His Met Lys Lys Ser Leu Glu Lys Phe Val Gly203520402045Asp Ala Thr Arg Leu Thr Asp Lys Leu Leu Glu Leu Cys Asn Lys Pro205020552060Val Asp Gly Ser Ser Ser Thr Leu Ser Met Ser Thr His Phe Lys Met2065207020752080Leu Lys Lys Leu Val Glu Glu Ala Thr Phe Ser Glu Ile Leu Ile Pro208520902095Leu Gln Ser Val Met Ile Pro Thr Leu Pro Ser Ile Leu Gly Thr His210021052110Ala Asn His Ala Ser His Glu Pro Phe Pro Gly His Trp Ala Tyr Ile211521202125Ala Gly Phe Asp Asp Met Val Glu Ile Leu Ala Ser Leu Gln Lys Pro213021352140Lys Lys Ile Ser Leu Lys Gly Ser Asp Gly Lys Phe Tyr Ile Met Met2145215021552160Cys Lys Pro Lys Asp Asp Leu Arg Lys Asp Cys Arg Leu Met Glu Phe216521702175Asn Ser Leu Ile Asn Lys Cys Leu Arg Lys Asp Ala Glu Ser Arg Arg218021852190Arg Glu Leu His Ile Arg Thr Tyr Ala Val Ile Pro Leu Asn Asp Glu219522002205Cys Gly Ile Ile Glu Trp Val Asn Asn Thr Ala Gly Leu Arg Pro Ile221022152220Leu Thr Lys Leu Tyr Lys Glu Lys Gly Val Tyr Met Thr Gly Lys Glu2225223022352240Leu Arg Gln Cys Met Leu Pro Lys Ser Ala Ala Leu Ser Glu Lys Leu224522502255Lys Val Phe Arg Glu Phe Leu Leu Pro Arg His Pro Pro Ile Phe His226022652270Glu Trp Phe Leu Arg Thr Phe Pro Asp Pro Thr Ser Trp Tyr Ser Ser227522802285Arg Ser Ala Tyr Cys Arg Ser Thr Ala Val Met Ser Met Val Gly Tyr229022952300Ile Leu Gly Leu Gly Asp Arg His Gly Glu Asn Ile Leu Phe Asp Ser2305231023152320Leu Thr Gly Glu Cys Val His Val Asp Phe Asn Cys Leu Phe Asn Lys232523302335Gly Glu Thr Phe Glu Val Pro Glu Ile Val Pro Phe Arg Leu Thr His234023452350Asn Met Val Asn Gly Met Gly Pro Met Gly Thr Glu Gly Leu Phe Arg235523602365Arg Ala Cys Glu Val Thr Met Arg Leu Met Arg Asp Gln Arg Glu Pro237023752380Leu Met Ser Val Leu Lys Thr Phe Leu His Asp Pro Leu Val Glu Trp2385239023952400Ser Lys Pro Val Lys Gly His Ser Lys Ala Pro Leu Asn Glu Thr Gly240524102415Glu Val Val Asn Glu Lys Ala Lys Thr His Val Leu Asp Ile Glu Gln242024252430Arg Leu Gln Gly Val Ile Lys Thr Arg Asn Arg Val Thr Gly Leu Pro243524402445Leu Ser Ile Glu Gly His Val His Tyr Leu Ile Gln Glu Ala Thr Asp245024552460Glu Asn Leu Leu Cys Gln Met Tyr Leu G1y Trp Thr Pro Tyr Met246524702475(2)SEQ ID NO19的说明(i)序列特征(A)长度23个碱基对(B)类型核苷酸(C)链型单链(D)拓扑结构线性(ii)分子类型DNA(vii)直接来源(B)克隆引物oDH26(xi)序列描述SEQ ID NO19TGGTTTCTGA GAACATTCCC TGA 23(2)SEQ ID NO20的说明(i)序列特征(A)长度9个氨基酸(B)类型氨基酸(D)拓扑结构线性(ii)分子类型肽(vii)直接来源(B)克隆FLAG标记(xi)序列描述SEQ ID NO20Met Asp Tyr Lys Asp Asp Asp Asp Lys1 5(2)SEQ ID NO21的说明(i)序列特征(A)长度20个碱基对(B)类型核苷酸(C)链型单链(D)拓扑结构线性(ii)分子类型DNA(vii)直接来源(B)克隆引物279-3(xi)序列描述SEQ ID NO21TGGATGATGA CAGCTGTGTC 20(2)SEQ ID NO22的说明(i)序列特征(A)长度20个碱基对(B)类型核苷酸(C)链型单链(D)拓扑结构线性(ii)分子类型DNA(vii)直接来源(B)克隆引物279-6(xi)序列描述SEQ ID NO22TGTAGTCGCT GCTCAATGTC 20(2)SEQ ID NO23的说明(i)序列特征(A)长度7624个碱基对(B)类型核苷酸(C)链型单链(D)拓扑结构线性(ii)分子类型cDNA(ix)特征(A)姓名/符号CDS(B)位置333..7562(xi)序列描述SEQ ID NO23CTTGTGAAGA GAATGTTTTA CACTCTIGTT AGTGAAGTTT ATTCTTTAAA AGTCAATCGT60CAAGGATTTA GCAAATGAAT TAGCACTTCG GATATACTTG TTTATTTAAT ATCTTTTTTG120TTTATTTCAA AGAATTCAGT AATTGGATCA TAACGAGACT TCTGCGGATT GCAGCAACTC180CCTCCTGTCA TTTGTTACAC AAGAAAATCT GTGAAGTCAT CTGTTCATTA TTATTTCTTT240TTAAAAGCAA GAGTCCTGCT ATTTTTGGGG TACTCACAAA AGAATTATTA CAACTTTTTG300AAGACTTGGT TTACCTCCAT AGAAGAAATG TG ATG GGT CAT GCT GTG GAA TGG 353Met Gly His Ala Val Glu Trp1 5CCA GTG GTC ATG AGC CGA TTT TTA AGT CAA TTA GAT GAA CAC ATG GGA 401Pro Val Val Met Ser Arg Phe Leu Ser Gln Leu Asp Glu His Met Gly10 15 20TAT TTA CAA TCA GCT CCT TTG CAG TTG ATG AGT ATG CAA AAT TTA GAA 449Tyr Leu Gln Set Ala Pro Leu Gln Leu Met Ser Met Gln Asn Leu Glu25 30 35TTT ATT GAA GTC ACT TTA TTA ATG GTT CTT ACT CGT ATT ATT GCA ATT 497Phe Ile Glu Val Thr Leu Leu Met Val Leu Thr Arg Ile Ile Ala Ile40 45 50 55GTG TTT TTT AGA AGG CAA GAA CTC TTA CTT TGG CAG ATA GGT TGT GTT 545Val Phe Phe Arg Arg Gln Glu Leu Leu Leu Trp Gln Ile Gly Cys Val60 65 70CTG CTA GAG TAT GGT AGT CCA AAA ATT AAA TCC CTA GCA ATT AGC TTT 593Leu Leu Glu Tyr Gly Ser Pro Lys Ile Lys Ser Leu Ala Ile Ser Phe75 80 85TTA ACA GAA CTT TTT CAG CTT GGA GGA CTA CCA GCA CAA CCA GCT AGC 641Leu Thr Glu Leu Phe Gln Leu Gly Gly Leu Pro Ala Gln Pro Ala Ser90 95 100ACT TTT TTC AGC TCA TTT TTG GAA TTA TTA AAA CAC CTT GTA GAA ATG 689Thr Phe Phe Ser Ser Phe Leu Glu Leu Leu Lys His Leu Val Glu Met105 110 115GAT ACT GAC CAA TTG AAA CTC TAT GAA GAG CCA TTA TCA AAG CTG ATA 737Asp Thr Asp Gln Leu Lys Leu Tyr Glu Glu Pro Leu Ser Lys Leu Ile120 125 130 135AAG ACA CTA TTT CCC TTT GAA GCA GAA GCT TAT AGA AAT ATT GAA CCT 785Lys Thr Leu Phe Pro Phe Glu Ala Glu Ala Tyr Arg Asn Ile Glu Pro140 145 150GTC TAT TTA AAT ATG CTG CTG GAA AAA CTC TGT GTC ATG TTT GAA GAC 833Val Tyr Leu Asn Met Leu Leu Glu Lys Leu Cys Val Met Phe Glu Asp155 160 165GGT GTG CTC ATG CGG CTT AAG TCT GAT TTG CTA AAA GCA GCT TTG TGC 881Gly Val Leu Met Arg Leu Lys Ser Asp Leu Leu Lys Ala Ala Leu Cys170 175 180CAT TTA CTG CAG TAT TTC CTT AAA TTT GTG CCA GCT GGG TAT GAA TCT 929His Leu Leu Gln Tyr Phe Leu Lys Phe Val Pro Ala Gly Tyr Glu Ser185 190 195GCT TTA CAA GTC AGG AAG GTC TAT GTG AGA AAT ATT TGT AAA GCT CTT 977Ala Leu Gln Val Arg Lys Val Tyr Val Arg Asn Ile Cys Lys Ala Leu200 205 210 215TTG GAT GTG CTT GGA ATT GAG GTA GAT GCA GAG TAC TTG TTG GGC CCA 1025Leu Asp Val Leu Gly Ile Glu Val Asp Ala Glu Tyr Leu Leu Gly Pro220 225 230CTT TAT GCA GCT TTG AAA ATG GAA AGT ATG GAA ATC ATT GAG GAG ATT 1073Leu Tyr Ala Ala Leu Lys Met Glu Ser Met Glu Ile Ile Glu Glu Ile235 240 245CAA TGC CAA ACT CAA CAG GAA AAC CTC AGC AGT AAT AGT GAT GGA ATA 1121Gln Cys Gln Thr Gln Gln Glu Asn Leu Ser Ser Asn Ser Asp Gly Ile250 255 260TCA CCC AAA AGG CGT CGT CTC AGC TCG TCT CTA AAC CCT TCT AAA AGA 1169Ser Pro Lys Arg Arg Arg Leu Ser Ser Ser Leu Asn Pro Ser Lys Arg265 270 275GCA CCA AAA CAG ACT GAG GAA ATT AAA CAT GTG GAC ATG AAC CAA AAG 1217Ala Pro Lys Gln Thr Glu Glu Ile Lys His Val Asp Met Asn Gln Lys280 285 290 295AGC ATA TTA TGG AGT GCA CTG AAA CAG AAA GCT GAA TCC CTT CAG ATT 1265Ser Ile Leu Trp Ser Ala Leu Lys Gln Lys Ala Glu Ser Leu Gln Ile300 305 310TCC CTT GAA TAC AGT GGC CTA AAG AAT CCT GTT ATT GAG ATG TTA GAA 1313Ser Leu Glu Tyr Ser Gly Leu Lys Asn Pro Val Ile Glu Met Leu Glu315 320 325GGA ATT GCT GTT GTC TTA CAA CTG ACT GCT CTG TGT ACT GTT CAT TGT 1361Gly Ile Ala Val Val Leu Gln Leu Thr Ala Leu Cys Thr Val His Cys330 335 340TCT CAT CAA AAC ATG AAC TGC CGT ACT TTC AAG GAC TGT CAA CAT AAA 1409Ser His Gln Asn Met Asn Cys Arg Thr Phe Lys Asp Cys Gln His Lys345 350 355TCC AAG AAG AAA CCT TCT GTA GTG ATA ACT TGG ATG TCA TTG GAT TTT 1450Ser Lys Lys Lys Pro Ser Val Val Ile Thr Trp Met Ser Leu Asp Phe360 365 370 375TAC ACA AAA GTG CTT AAG AGC TGT AGA AGT TTG TTA GAA TCT GTT CAG 1505Tyr Thr Lys Val Leu Lys Ser Cys Arg Ser Leu Leu Glu Ser Val Gln380 385 390AAA CTG GAC CTG GAG GCA ACC ATT GAT AAG GTG GTG AAA ATT TAT GAT 1553Lys Leu Asp Leu Glu Ala Thr Ile Asp Lys Val Val Lys Ile Tyr Asp395 400 405GCT TTG ATT TAT ATG CAA GTA AAC AGT TCA TTT GAA GAT CAT ATC CTG 1601Ala Leu Ile Tyr Met Gln Val Asn Ser Ser Phe Glu Asp His Ile Leu410 415 420GAA GAT TTA TGT GGA ATG CTC TCA CTT CCA TGG ATT TAT TCC CAT TCT 1645Glu Asp Leu Cys Gly Met Leu Ser Leu Pro Trp Ile Tyr Ser His Ser425 430 435GAT GAT GGC TGT TTA AAG TTG ACC ACA TTT GCC GCT AAT CTT CTA ACA 1697Asp Asp Gly Cys Leu Lys Leu Thr Thr Phe Ala Ala Asn Leu Leu Thr440 445 450 455TTA AGC TGT AGG ATT TCA GAT AGC TAT TCA CCA CAG GCA CAA TCA CGA 1745Leu Ser Cys Arg Ile Ser Asp Ser Tyr Ser Pro Gln Ala Gln Ser Arg460 465 470TGT GTG TTT CTT CTG ACT CTG TTT CCA AGA AGA ATA TTC CTT GAG TGG 1793Cys Val Phe Leu Leu Thr Leu Phe Pro Arg Arg Ile Phe Leu Glu Trp475 480 485AGA ACA GCA GTT TAC AAC TGG GCC CTG CAG AGC TCC CAT GAA GTA ATC 1841Arg Thr Ala Val Tyr Asn Trp Ala Leu Gln Ser Ser His Glu Val Ile490 495 500CGG GCT AGT TGT GTT AGT GGA TTT TTT ATC TTA TTG CAG CAG CAG AAT 1889Arg Ala Ser Cys Val Ser Gly Phe Phe Ile Leu Leu Gln Gln Gln Asn505 510 515TCT TGT AAC AGA GTT CCC AAG ATT CTT ATA GAT AAA GTC AAA GAT GAT 1937Ser Cys Asn Arg Val Pro Lys Ile Leu Ile Asp Lys Val Lys Asp Asp520 525 530 535TCT GAC ATT GTC AAG AAA GAA TTT GCT TCT ATA CTT GGT CAA CTT GTC 1985Ser Asp Ile Val Lys Lys Glu Phe Ala Ser Ile Leu Gly Gln Leu Val540 545 550TGT ACT CTT CAC GGC ATG TTT TAT CTG ACA AGT TCT TTA ACA GAA CCT 2033Cys Thr Leu His Gly Met Phe Tyr Leu Thr Ser Ser Leu Thr Glu Pro555 560 565TTC TCT GAA CAC GGA CAT GTG GAC CTC TTC TGT AGG AAC TTG AAA GCC 2081Phe Ser Glu His Gly His Val Asp Leu Phe Cys Arg Asn Leu Lys Ala570 575 580ACT TCT CAA CAT GAA TGT TCA TCT TCT CAA CTA AAA GCT TCT GTC TGC 2129Thr Ser Gln His Glu Cys Ser Ser Ser Gln Leu Lys Ala Ser Val Cys585 590 595AAG CCA TTC CTT TTC CTA CTG AAA AAA AAA ATA CCT AGT CCA GTA AAA 2177Lys Pro Phe Leu Phe Leu Leu Lys Lys Lys Ile Pro Ser Pro Val Lys600 605 610 615CTT GCT TTC ATA GAT AAT CTA CAT CAT CTT TGT AAG CAT CTT GAT TTT 2225Leu Ala Phe Ile Asp Asn Leu His His Leu Cys Lys His Leu Asp Phe620 625 630AGA GAA GAT GAA ACA GAT GTA AAA GCA GTT CTT GGA ACT TTA TTA AAT 2273Arg Glu Asp Glu Thr Asp Val Lys Ala Val Leu Gly Thr Leu Leu Asn635 640 645TTA ATG GAA GAT CCA GAC AAA GAT GTT AGA GTG GCT TTT AGT GGA AAT 2321Leu Met Glu Asp Pro Asp Lys Asp Val Arg Val Ala Phe Ser Gly Asn650 655 660ATC AAG CAC ATA TTG GAA TCC TTG GAC TCT GAA GAT GGA TTT ATA AAG 2369Ile Lys His Ile Leu Glu Ser Leu Asp Ser Glu Asp Gly Phe Ile Lys665 670 675GAG CTT TTT GTC TTA AGA ATG AAG GAA GCA TAT ACA CAT GCC CAA ATA 2417Glu Leu Phe Val Leu Arg Met Lys Glu Ala Tyr Thr His Ala Gln Ile680 685 690 695TCA AGA AAT AAT GAG CTG AAG GAT ACC TTG ATT CTT ACA ACA GGG GAT 2465Ser Arg Asn Asn Glu Leu Lys Asp Thr Leu Ile Leu Thr Thr Gly Asp700 705 710ATT GGA AGG GCC GCA AAA GGA GAT TTG GTA CCA TTT GCA CTC TTA CAC 2513Ile Gly Arg Ala Ala Lys Gly Asp Leu Val Pro Phe Ala Leu Leu His715 720 725TTA TTG CAT TGT TTG TTA TCC AAG TCA GCA TCT GTC TCT GGA GCA GCA 2561Leu Leu His Cys Leu Leu Ser Lys Ser Ala Ser Val Ser Gly Ala Ala730 735 740TAC ACA GAA ATT AGA GCT CTG GTT GCA GCT AAA AGT GTT AAA CTG CAA 2609Tyr Thr Glu Ile Arg Ala Leu Val Ala Ala Lys Ser Val Lys Leu Gln745 750 755AGT TTT TTC AGC CAG TAT AAG AAA CCC ATC TGT CAG TTT TTG GTA GAA 2657Ser Phe Phe Ser Gln Tyr Lys Lys Pro Ile Cys Gln Phe Leu Val Glu760 765 770 775TCC CTT CAC TCT AGT CAG ATG ACA GCA CTT CCG AAT ACT CCA TGC CAG 2705Ser Leu His Ser Ser Gln Met Thr Ala Leu Pro Asn Thr Pro Cys Gln780 785 790AAT GCT GAC GTG CGA AAA CAA GAT GTG GCT CAC CAG AGA GAA ATG GCT 2753Asn Ala Asp Val Arg Lys Gln Asp Val Ala His Gln Arg Glu Met Ala795 800 805TTA AAT ACG TTG TCT GAA ATT GCC AAC GTT TTC GAC TTT CCT GAT CTT 2801Leu Asn Thr Leu Ser Glu Ile Ala Asn Val Phe Asp Phe Pro Asp Leu810 815 820AAT CGT TTT CTT ACT AGG ACA TTA CAA GTT CTA CTA CCT GAT CTT GCT 2849Asn Arg Phe Leu Thr Arg Thr Leu Gln Val Leu Leu Pro Asp Leu Ala825 830 835GCC AAA GCA AGC CCT GCA GCT TCT GCT CTC ATT CGA ACT TTA GGA AAA 2897Ala Lys Ala Ser Pro Ala Ala Ser Ala Leu Ile Arg Thr Leu Gly Lys840 845 850 855CAA TTA AAT GTC AAT CGT AGA GAG ATT TTA ATA AAC AAC TTC AAA TAT 2945Gln Leu Asn Val Asn Arg Arg Glu Ile Leu Ile Asn Asn Phe Lys Tyr860 865 870ATT TTT TCT CAT TTG GTC TGT TCT TGT TCC AAA GAT GAA TTA GAA CGT 2993Ile Phe Ser His Leu Val Cys Ser Cys Ser Lys Asp Glu Leu Glu Arg875 880 885GCC CTT CAT TAT CTG AAG AAT GAA ACA GAA ATT GAA CTG GGG AGC CTG 3041Ala Leu His Tyr Leu Lys Asn Glu Thr Glu Ile Glu Leu Gly Ser Leu890 895 900TTG AGA CAA GAT TTC CAA GGA TTG CAT AAT GAA TTA TTG CTG CGT ATT 3089Leu Arg Gln Asp Phe Gln Gly Leu His Asn Glu Leu Leu Leu Arg Ile905 910 915GGA GAA CAC TAT CAA CAG GTT TTT AAT GGT TTG TCA ATA CTT GCC TCA 3237Gly Glu His Tyr Gln Gln Val Phe Asn Gly Leu Ser Ile Leu Ala Ser920 925 930 935TTT GCA TCC AGT GAT GAT CCA TAT CAG GGC CCG AGA GAT ATC ATA TCA 3185Phe Ala Ser Ser Asp Asp Pro Tyr Gln Gly Pro Arg Asp Ile Ile Ser940 945 950CCT GAA CTG ATG GCT GAT TAT TTA CAA CCC AAA TTG TTG GGC ATT TTG 3233Pro Glu Leu Met Ala Asp Tyr Leu Gln Pro Lys Leu Leu Gly Ile Leu955 960 965GCT TTT TTT AAC ATG CAG TTA CTG AGC TCT AGT GTT GGC ATT GAA GAT 3281Ala Phe Phe Asn Met Gln Leu Leu Ser Ser Ser Val Gly Ile Glu Asp970 975 980AAG AAA ATG GCC TTG AAC AGT TTG ATG TCT TTG ATG AAG TTA ATG GGA 3329Lys Lys Met Ala Leu Asn Ser Leu Met Ser Leu Met Lys Leu Met Gly985 990 995CCC AAA CAT GTC AGT TCT GTG AGG GTG AAG ATG ATG ACC ACA CTG AGA 3377Pro Lys His Val Ser Ser Val Arg Val Lys Met Met Thr Thr Leu Arg1000100510101015ACT GGC CTT CGA TTC AAG GAT GAT TTT CCT GAA TTG TGT TGC AGA GCT 3425Thr Gly Leu Arg Phe Lys Asp Asp Phe Pro Glu Leu Cys Cys Arg Ala102010251030TGG GAC TGC TTT GTT CGC TGC CTG GAT CAT GCT TGT CTG GGC TCC CTT 3473Trp Asp Cys Phe Val Arg Cys Leu Asp His Ala Cys Leu Gly Ser Leu103510401045CTC AGT CAT GTA ATA GTA GCT TTG TTA CCT CTT ATA CAC ATC CAG CCT 3521Leu Ser His Val Ile Val Ala Leu Leu Pro Leu Ile His Ile Gln Pro105010551060AAA GAA ACT GCA GCT ATC TTC CAC TAC CTC ATA ATT GAA AAC AGG GAT 3569Lys Glu Thr Ala Ala Ile Phe His Tyr Leu Ile Ile Glu Asn Arg Asp106510701075GCT GTG CAA GAT TTT CTT CAT GAA ATA TAT TTT TTA CCT GAT CAT CCA 3617Ala Val Gln Asp Phe Leu His Glu Ile Tyr Phe Leu Pro Asp His Pro1080108510901095GAA TTA AAA AAG ATA AAA GCC GTT CTC CAG GAA TAC AGA AAG GAG ACC 3665Glu Leu Lys Lys Ile Lys Ala Val Leu Gln Glu Tyr Arg Lys Glu Thr110011051110TCT GAG AGC ACT GAT CTT CAG ACA ACT CTT CAG CTC TCT ATG AAG GCC 3713Ser Glu Ser Thr Asp Leu Gln Thr Thr Leu Gln Leu Ser Met Lys Ala111511201125ATT CAA CAT GAA AAT GTC GAT GTT CGT ATT CAT GCT CTT ACA AGC TTG 3761Ile Gln His Glu Asn Val Asp Val Arg Ile His Ala Leu Thr Ser Leu113011351140AAG GAA ACC TTG TAT AAA AAT CAG GAA AAA CTG ATA AAG TAT GCA ACA 3809Lys Glu Thr Leu Tyr Lys Asn Gln Glu Lys Leu Ile Lys Tyr Ala Thr114511501155GAC AGT GAA ACA GTA GAA CCT ATT ATC TCA CAG TTG GTG ACA GTG CTT 3857Asp Ser Glu Thr Val Glu Pro Ile Ile Ser Gln Leu Val Thr Val Leu1160116511701175TTG AAA GGT TGC CAA GAT GCA AAC TCT CAA GCT CGG TTG CTC TGT GGG 3905Leu Lys Gly Cys Gln Asp Ala Asn Ser Gln Ala Arg Leu Leu Cys Gly118011851190GAA TGT TTA GGG GAA TTG GGG GCG ATA GAT CCA GGT CGA TTA GAT TTC 3953Glu Cys Leu Gly Glu Leu Gly Ala Ile Asp Pro Gly Arg Leu Asp Phe119512001205TCA ACA ACT GAA ACT CAA GGA AAA GAT TTT ACA TTT GTG ACT GGA GTA 4001Ser Thr Thr Glu Thr Gln Gly Lys Asp Phe Thr Phe Val Thr Gly Val121012151220GAA GAT TCA AGC TTT GCC TAT GGA TTA TTG ATG GAG CTA ACA AGA GCT 4049Glu Asp Ser Ser Phe Ala Tyr Gly Leu Leu Met Glu Leu Thr Arg Ala122512301235TAC CTT GCG TAT GCT GAT AAT AGC CGA GCT CAA GAT TCA GCT GCC TAT 4097Tyr Leu Ala Tyr Ala Asp Asn Ser Arg Ala Gln Asp Ser Ala Ala Tyr1240124512501255GCC ATT CAG GAG TTG CTT TCT ATT TAT GAC TGT AGA GAG ATG GAG ACC 4145Ala Ile Gln Glu Leu Leu Ser Ile Tyr Asp Cys Arg Glu Met Glu Thr126012651270AAC GGC CTA GGT CAC CAA TTG TGG AGG AGA TTT CCT GAG CAT GTT CGG 4193Asn Glu Pro Gly His Gln Leu Trp Arg Arg Phe Pro Glu His Val Arg127512801285GAA ATA CTA GAA CCT CAT CTA AAT ACC AGA TAC AAG AGT TCT CAG AAG 4241Glu Ile Leu Glu Pro His Leu Asn Thr Arg Tyr Lys Ser Ser Gln Lys129012951300TCA ACC GAT TGG TCT GGA GTA AAG AAG CCA ATT TAC TTA AGT AAA TTG 4289Ser Thr Asp Trp Ser Gly Val Lys Lys Pro Ile Tyr Leu Sar Lys Leu130513101315GGT AGT AAC TTT GCA GAA TGG TCA GCA TCT TGG GCA GGT TAT CTT ATT 4337Gly Ser Asn Phe Ala Glu Trp Ser Ala Ser Trp Ala Gly Tyr Leu Ile1320132513301335ACA AAG GTT CGA CAT GAT CTT GCC AGT AAA ATT TTC ACC TGC TGT AGC 4385Thr Lys Val Arg His Asp Leu Ala Ser Lys Ile Phe Thr Cys Cys Ser134013451350ATT ATG ATG AAG CAT GAT TTC AAA GTG ACC ATC TAT CTT CTT CCA CAT 4433Ile Met Met Lys His Asp Phe Lys Val Thr Ile Tyr Leu Leu Pro His135513601365ATT CTG GTG TAT GTC TTA CTG GGT TGT AAT CAA GAA GAT CAG CAG GAG 4481Ile Leu Val Tyr Val Leu Leu Gly Cys Asn Gln Glu Asp Gln Gln Glu137013751380GTT TAT GCA GAA ATT ATG GCA GTT CTA AAG CAT GAC GAT CAG CAT ACC 4529Val Tyr Ala Glu Ile Met Ala Val Leu Lys His Asp Asp Gln His Thr138513901395ATA AAT ACC CAA GAC ATT GCA TCT GAT CTG TGT CAA CTC AGT ACA CAG 4577Ile Asn Thr Gln Asp Ile Ala Ser Asp Leu Cys Gln Leu Ser Thr Gln1400140514101415ACT GTG TTC TCC ATG CTT GAC CAT CTC ACA CAG TGG GCA AGG CAC AAA 4625Thr Val Phe Ser Met Leu Asp His Leu Thr Gln Trp Ala Arg His Lys142014251430TTT CAG GCA CTG AAA GCT GAG AAA TGT CCA CAC AGC AAA TCA AAC AGA 4673Phe Gln Ala Leu Lys Ala Glu Lys Cys Pro His Ser Lys Ser Asn Arg143514401445AAT AAG GTA GAC TCA ATG GTA TCT ACT GTG GAT TAT GAA GAC TAT CAG 4721Asn Lys Val Asp Ser Met Val Ser Thr Val Asp Tyr Glu Asp Tyr Gln145014551460AGT GTA ACC CGT TTT CTA GAC CTC ATA CCC CAG GAT ACT CTG GCA GTA 4769Ser Val Thr Arg Phe Leu Asp Leu Ile Pro Gln Asp Thr Leu Ala Val146514701475GCT TCC TTT CGC TCC AAA GCA TAC ACA CGA GCT GTA ATG CAC TTT GAA 4817Ala Ser Phe Arg Ser Lys Ala Tyr Thr Arg Ala Val Met His Phe Glu1480148514901495TCA TTT ATT ACA GAA AAG AAG CAA AAT ATT CAG GAA CAT CTT GGA TTT 4865Ser Phe Ile Thr Glu Lys Lys Gln Asn Ile Gln Glu His Leu Gly Phe150015051510TTA CAG AAA TTG TAT GCT GCT ATG CAT GAA CCT GAT GGA GTG GCC GGA 4913Leu Gln Lys Leu Tyr Ala Ala Met His Glu Pro Asp Gly Val Ala Gly151515201525GTC AGT GCA ATT AGA AAG GCA GAA CCA TCT CTA AAA GAA CAG ATC CTT 4961Val Ser Ala Ile Arg Lys Ala Glu Pro Ser Leu Lys Glu Gln Ile Leu153015351540GAA CAT GAA AGC CTT GGC TTG CTG AGG GAT GCC ACT GCT TGT TAT GAC 5009Glu His Glu Ser Leu Gly Leu Leu Arg Asp Ala Thr Ala Cys Tyr Asp154515501555AGG GCT ATT CAG CTA GAA CCA GAC CAG ATC ATT CAT TAC CAT GGT GTA 5057Arg Ala Ile Gln Leu Glu Pro Asp Gln Ile Ile His Tyr His Gly Val1560156515701575GTA AAG TCC ATG TTA GGT CTT GGT CAG CTG TCT ACT GTT ATC ACT CAG 5105Val Lys Ser Met Leu Gly Leu Gly Gln Leu Ser Thr Val Ile Thr Gln158015851590GTG AAT GGA GTG CAT GCT AAC AGG TCC GAG TGG ACA GAT GAA TTA AAC 5153Val Asn Gly Val His Ala Asn Arg Ser Glu Trp Thr Asp Glu Leu Asn159516001605ACG TAC AGA GTG GAA GCA GCT TGG AAA TTG TCA CAG TGG GAT TTG GTG 5201Thr Tyr Arg Val Glu Ala Ala Trp Lys Leu Ser Gln Trp Asp Leu Val161016151620GAA AAC TAT TTG GCA GCA GAT GGA AAA TCT ACA ACA TGG AGT GTC AGA 5245Glu Asn Tyr Leu Ala Ala Asp Gly Lys Ser Thr Thr Trp Ser Val Arg162516301635CTG GGA CAG CTA TTA TTA TCA GCC AAA AAA AGA GAT ATC ACA GCT TTT 5297Leu Gly Gln Leu Leu Leu Ser Ala Lys Lys Arg Asp Ile Thr Ala Phe1640164516501655TAT GAC TCA CTG AAA CTA GTG AGA GCA GAA CAA ATT GTA CCT CTT TCA 5345Tyr Asp Ser Leu Lys Leu Val Arg Ala Glu Gln Ile Val Pro Leu Ser166016651670GCT GCA AGC TTT GAA AGA GGC TCC TAC CAA CGA GGA TAT GAA TAT ATT 5393Ala Ala Ser Phe Glu Arg Gly Ser Tyr Gln Arg Gly Tyr Glu Tyr Ile167516801685GTG AGA TTG CAC ATG TTA TGT GAG TTG GAG CAT AGC ATC AAA CCA CTT 5441Val Arg Leu His Met Leu Cys Glu Leu Glu His Ser Ile Lys Pro Leu169016951700TTC CAG CAT TCT CCA GGT GAC AGT TCT CAA GAA GAT TCT CTA AAC TGG 5485Phe Gln His Ser Pro Gly Asp Ser Ser Gln Glu Asp Ser Leu Asn Trp170517101715GTA GCT CGA CTA GAA ATG ACC CAG AAT TCC TAC AGA GCC AAG GAG CCT 5537Val Ala Arg Leu Glu Met Thr Gln Asn Ser Tyr Arg Ala Lys Glu Pro1720172517301735ATC CTG GCT CTC CGG AGG GCT TTA CTA AGC CTC AAC AAA AGA CCA GAT 5585Ile Leu Ala Leu Arg Arg Ala Leu Leu Ser Leu Asn Lys Arg Pro Asp174017451750TAC AAT GAA ATG GTT GGA GAA TGC TGG CTG CAG AGT GCC AGG GTA GCT 5633Tyr Asn Glu Met Val Gly Glu Cys Trp Leu Gln Ser Ala Arg Val Ala175517601765AGA AAG GCT GGT CAC CAC CAG ACA GCC TAC AAT GCT CTC CTT AAT GCA 5681Arg Lys Ala Gly His His Gln Thr Ala Tyr Asn Ala Leu Leu Asn Ala177017751780GGG GAA TCA CGA CTC GCT GAA CTG TAC GTG GAA AGG GCA AAG TGG CTC 5729Gly Glu Ser Arg Leu Ala Glu Leu Tyr Val Glu Arg Ala Lys Trp Leu178517901795TGG TCC AAG GGT GAT GTT CAC CAG GCA CTA ATT GTT CTT CAA AAA GGT 5777Trp Ser Lys Gly Asp Val His Gln Ala Leu Ile Val Leu Gln Lys Gly1800180518101815GTT GAA TTA TGT TTT CCT GAA AAT GAA ACC CCA CCT GAG GGT AAG AAC 5825Val Glu Leu Cys Phe Pro Glu Asn Glu Thr Pro Pro Glu Gly Lys Asn182018251830ATG TTA ATC CAT GGT CGA GCT ATG CTA CTA GTG GGC CGA TTT ATG GAA 5573Met Leu Ile His Gly Arg Ala Met Leu Leu Val Gly Arg Phe Met Glu183518401845GAA ACA GCT AAC TTT GAA AGC AAT GCA ATT ATG AAA AAA TAT AAG GAT 5921Glu Thr Ala Asn Phe Glu Ser Asn Ala Ile Met Lys Lys Tyr Lys Asp185018551860GTG ACC GCG TGC CTG CCA GAA TGG GAG GAT GGG CAT TTT TAC CTT GCC 5969Val Thr Ala Cys Leu Pro Glu Trp Glu Asp Gly His Phe Tyr Leu Ala186518701875AAG TAC TAT GAC AAA TTG ATG CCC ATG GTC ACA GAC AAC AAA ATG GAA 6017Lys Tyr Tyr Asp Lys Leu Met Pro Met Val Thr Asp Asn Lys Met Glu1880188518901895AAG CAA GGT GAT CTC ATC CGG TAT ATA GTT CTT CAT TTT GGC AGA TCT 6065Lys Gln Gly Asp Leu Ile Arg Tyr Ile Val Leu His Phe Gly Arg Ser190019051910CTA CAA TAT GGA AAT CAG TTC ATA TAT CAG TCA ATG CCA CGA ATG TTA 6113Leu Gln Tyr Gly Asn Gln Phe Ile Tyr Gln Ser Met Pro Arg Met Leu191519201925ACT CTA TGG CTT GAT TAT GGT ACA AAG GCA TAT GAA TGG GAA AAA GCT 6161Thr Leu Trp Leu Asp Tyr Gly Thr Lys Ala Tyr Glu Trp Glu Lys Ala193019351940GGC CGC TCC GAT CGT GTA CAA ATG AGG AAT GAT TTG GGT AAA ATA AAC 6209Gly Arg Ser Asp Arg Val Gln Met Arg Asn Asp Leu Gly Lys Ile Asn194519501955AAG GTT ATC ACA GAG CAT ACA AAC TAT TTA GCT CCA TAT CAA TTT TTG 6257Lys Val Ile Thr Glu His Thr Asn Tyr Leu Ala Pro Tyr Gln Phe Leu1960196519701975ACT GCT TTT TCA CAA TTG ATC TCT CGA ATT TGT CAT TCT CAC GAT GAA 6305Thr Ala Phe Ser Gln Leu Ile Ser Arg Ile Cys His Ser His Asp Glu198019851990GTT TTT GTT GTG CTT GAT GGA AAT AAT AGC CAA GTA TTT CTA GCC TAT 6353Val Phe Val Val Leu Asp Gly Asn Asn Ser Gln Val Phe Leu Ala Tyr199520002005CCT CAA CAA GCA ATG TGG ATG ATG ACA GCT GTG TCA AAG TCA TCT TAT 6401Pro Gln Gln Ala Met Trp Met Met Thr Ala Val Ser Lys Ser Ser Tyr201020152020CCC ATG CGT GTG AAC AGA TGC AAG GAA ATC CTC AAT AAA GCT ATT CAT 6449Pro Met Arg Val Asn Arg Cys Lys Glu Ile Leu Asn Lys Ala Ile His202520302035ATG AAA AAA TCC TTA GAG AAG TTT GTT GGA GAT GCA ACT CGC CTA ACA 6497Met Lys Lys Ser Leu Glu Lys Phe Val Gly Asp Ala Thr Arg Leu Thr2040204520502055GAT AAG CTT CTA GAA TTG TGC AAT AAA CCG GTG GAA ATT CTT GCT TCT 6545Asp Lys Leu Leu Glu Leu Cys Asn Lys Pro Val Glu Ile Leu Ala Ser206020652070CTT CAG AAA CCA AAG AAG ATT TCT TTA AAA GGC TCA GAT GGA AAG TTC 6593Leu Gln Lys Pro Lys Lys Ile Ser Leu Lys Gly Ser Asp Gly Lys Phe207520802085TAC ATC ATG ATG TGT AAG CCA AAA GAT GAC CTG AGA AAG GAT TGT AGA 6641Tyr Ile Met Met Cys Lys Pro Lys Asp Asp Leu Arg Lys Asp Cys Arg209020952100CTA ATG GAA TTC AAT TCC TTG ATT AAT AAG TGC TTA AGA AAA GAT GCA 6689Leu Met Glu Phe Asn Ser Leu Ile Asn Lys Cys Leu Arg Lys Asp Ala210521102115GAG TCT CGT AGA AGA GAA CTT CAT ATT CGA ACA TAT GCA GTT ATT CCA 6737Glu Ser Arg Arg Arg Glu Leu His Ile Arg Thr Tyr Ala Val Ile Pro2120212521302135CTA AAT GAT GAA TGT GGG ATT ATT GAA TGG GTG AAC AAC ACT GCT GGT 6785Leu Asn Asp Glu Cys Gly Ile Ile Glu Trp Val Asn Asn Thr Ala G1y214021452150TTG AGA CCT ATT CTG ACC AAA CTA TAT AAA GAA AAG GGA GTG TAT ATG 6833Leu Arg Pro Ile Leu Thr Lys Leu Tyr Lys Glu Lys Gly Val Tyr Met215521602165ACA GGA AAA GAA CTT CGC CAG TGT ATG CTA CCA AAG TCA GCA GCT TTA 6881Thr Gly Lys Glu Leu Arg Gln Cys Met Leu Pro Lys Ser Ala Ala Leu217021752180TCT GAA AAA CTC AAA GTA TTC CGA GAA TTT CTC CTG CCC AGG CAT CCT 6929Ser Glu Lys Leu Lys Val Phe Arg Glu Phe Leu Leu Pro Arg His Pro218521902195CCT ATT TTT CAT GAG TGG TTT CTG AGA ACA TTC CCT GAT CCT ACA TCA 6977Pro Ile Phe His Glu Trp Phe Leu Arg Thr Phe Pro Asp Pro Thr Ser2200220522102215TGG TAC AGT AGT AGA TCA GCT TAC TGC CGT TCC ACT GCA GTA ATG TCA 7025Trp Tyr Ser Ser Arg Ser Ala Tyr Cys Arg Ser Thr Ala Val Met Ser222022252230ATG GTT GGT TAT ATT CTG GGG CTT GGA GAC CGT CAT GGT GAA AAT ATT 7073Met Val Gly Tyr Ile Leu Gly Leu Gly Asp Arg His Gly Glu Asn Ile223522402245CTC TTT GAT TCT TTG ACT GGT GAA TGC GTA CAT GTA GAT TTC AAT TGT 7121Leu Phe Asp Ser Leu Thr Gly Glu Cys Val His Val Asp Phe Asn Cys225022552260CTT TTC AAT AAG GGA GAA ACC TTT GAA GTT CCA GAA ATT GTG CCA TTT 7163Leu Phe Asn Lys Gly Glu Thr Phe Glu Val Pro Glu Ile Val Pro Phe226522702275CGC CTG ACT CAT AAT ATG GTT AAT GGA ATG GGT CCT ATG GGA ACA GAG 7217Arg Leu Thr His Asn Met Val Asn Gly Met Gly Pro Met Gly Thr Glu2280228522902295GGT CTT TTT CGA AGA GCA TGT GAA GTT ACA ATG AGG CTG ATG CGT GAT 7265Gly Leu Phe Arg Arg Ala Cys Glu Val Thr Met Arg Leu Met Arg Asp230023052310CAG CGA GAG CCT TTA ATG AGT GTC TTA AAG ACT TTT CTA CAT GAT CCT 7313Gln Arg Glu Pro Leu Met Ser Val Leu Lys Thr Phe Leu His Asp Pro231523202325CTT GTG GAA TGG AGT AAA CCA GTG AAA GGG CAT TCC AAA GCG CCA CTG 7361Leu Val Glu Trp Ser Lys Pro Val Lys Gly His Ser Lys Ala Pro Leu233023352340AAT GAA ACT GGA GAA GTT GTC AAT GAA AAG GCC AAG ACC CAT GTT CTT 7409Asn Glu Thr Gly Glu Val Val Asn Glu Lys Ala Lys Thr His Val Leu234523502355GAC ATT GAG CAG CGA CTA CAA GGT GTA ATC AAG ACT CGA AAT AGA GTG 7457Asp Ile Glu Gln Arg Leu Gln Gly Val Ile Lys Thr Arg Asn Arg Val2360236523702375ACA GGA CTG CCG TTA TCT ATT GAA GGA CAT GTG CAT TAC CTT ATA CAA 7505Thr Gly Leu Pro Leu Ser Ile Glu Gly His Val His Tyr Leu Ile Gln238023852390GAA GCT ACT GAT GAA AAC TTA CTA TGC CAG ATG TAT CTT GGT TGG ACT 7553Glu Ala Thr Asp Glu Asn Leu Leu Cys Gln Met Tyr Leu Gly Trp Thr239524002405CCA TAT ATG TGAAATGAAA TTATGTAAAA GAATATGTTA ATAATCTAAA 7602Pro Tyr Met2410AGTAAAAAAA AAAAAAAAAA AA 7624(2)SEQ ID NO24的说明(i)序列特征(A)长度2410个氨基酸(B)类型氨基酸(D)拓扑结构线性(ii)分子类型蛋白(xi)序列描述SEQ ID NO24Met Gly His Ala Val Glu Trp Pro Val Val Met Ser Arg Phe Leu Ser1 5 10 15Gln Leu Asp Glu His Met Gly Tyr Leu Gln Ser Ala Pro Leu Gln Leu20 25 30Met Ser Met Gln Asn Leu Glu Phe Ile Glu Val Thr Leu Leu Met Val35 40 45Leu Thr Arg Ile Ile Ala Ile Val Phe Phe Arg Arg Gln Glu Leu Leu50 55 60Leu Trp Gln Ile Gly Cys Val Leu Leu Glu Tyr Gly Ser Pro Lys Ile65 70 75 80Lys Ser Leu Ala Ile Ser Phe Leu Thr Glu Leu Phe Gln Leu Gly Gly85 90 95Leu Pro Ala Gln Pro Ala Ser Thr Phe Phe Ser Ser Phe Leu Glu Leu100 105 110Leu Lys His Leu Val Glu Met Asp Thr Asp Gln Leu Lys Leu Tyr Glu115 120 125Glu Pro Leu Ser Lys Leu Ile Lys Thr Leu Phe Pro Phe Glu Ala Glu130 135 140Ala Tyr Arg Asn Ile Glu Pro Val Tyr Leu Asn Met Leu Leu Glu Lys145 150 155 160Leu Cys Val Met Phe Glu Asp Gly Val Leu Met Arg Leu Lys Ser Asp165 170 175Leu Leu Lys Ala Ala Leu Cys His Leu Leu Gln Tyr Phe Leu Lys Phe180 185 190Val Pro Ala Gly Tyr Glu Ser Ala Leu Gln Val Arg Lys Val Tyr Val195 200 205Arg Asn Ile Cys Lys Ala Leu Leu Asp Val Leu Gly Ile Glu Val Asp210 215 220Ala Glu Tyr Leu Leu Gly Pro Leu Tyr Ala Ala Leu Lys Met Glu Ser225 230 235 240Met Glu Ile Ile Glu Glu Ile Gln Cys Gln Thr Gln Gln Glu Asn Leu245 250 255Ser Ser Asn Ser Asp Gly Ile Ser Pro Lys Arg Arg Arg Leu Ser Ser260 265 270Ser Leu Asn Pro Ser Lys Arg Ala Pro Lys Gln Thr Glu Glu Ile Lys275 280 285His Val Asp Met Asn Gln Lys Ser Ile Leu Trp Ser Ala Leu Lys Gln290 295 300Lys Ala Glu Ser Leu Gln Ile Ser Leu Glu Tyr Ser Gly Leu Lys Asn305 310 315 320Pro Val Ile Glu Met Leu Glu Gly Ile Ala Val Val Leu Gln Leu Thr325 330 335Ala Leu Cys Thr Val His Cys Ser His Gln Asn Met Asn Cys Arg Thr340 345 350Phe Lys Asp Cys Gln His Lys Ser Lys Lys Lys Pro Ser Val Val Ile355 360 365Thr Trp Met Ser Leu Asp Phe Tyr Thr Lys Val Leu Lys Ser Cys Arg370 375 380Ser Leu Leu Glu Ser Val Gln Lys Leu Asp Leu Glu Ala Thr Ile Asp385 390 395 400Lys Val Val Lys Ile Tyr Asp Ala Leu Ile Tyr Met Gln Val Asn Ser405 410 415Ser Phe Glu Asp His Ile Leu Glu Asp Leu Cys Gly Met Leu Ser Leu420 425 430Pro Trp Ile Tyr Ser His Ser Asp Asp Gly Cys Leu Lys Leu Thr Thr435 440 445Phe Ala Ala Asn Leu Leu Thr Leu Ser Cys Arg Ile Ser Asp Ser Tyr450 455 460Ser Pro Gln Ala Gln Ser Arg Cys Val Phe Leu Leu Thr Leu Phe Pro465 470 475 480Arg Arg Ile Phe Leu Glu Trp Arg Thr Ala Val Tyr Asn Trp Ala Leu485 490 495Gln Ser Ser His Glu Val Ile Arg Ala Ser Cys Val Ser Gly Phe Phe500 505 510Ile Leu Leu Gln Gln Gln Asn Ser Cys Asn Arg Val Pro Lys Ile Leu515 520 525Ile Asp Lys Val Lys Asp Asp Ser Asp Ile Val Lys Lys Glu Phe Ala530 535 540Ser Ile Leu Gly Gln Leu Val Cys Thr Leu His Gly Met Phe Tyr Leu545 550 555 560Thr Ser Ser Leu Thr Glu Pro Phe Ser Glu His Gly His Val Asp Leu565 570 575Phe Cys Arg Asn Leu Lys Ala Thr Ser Gln His Glu Cys Ser Ser Ser580 585 590Gln Leu Lys Ala Ser Val Cys Lys Pro Phe Leu Phe Leu Leu Lys Lys595 600 605Lys Ile Pro Ser Pro Val Lys Leu Ala Phe Ile Asp Asn Leu His His610 615 620Leu Cys Lys His Leu Asp Phe Arg Glu Asp Glu Thr Asp Val Lys Ala625 630 635 640Val Leu Gly Thr Leu Leu Asn Leu Met Glu Asp Pro Asp Lys Asp Val645 650 655Arg Val Ala Phe Ser Gly Asn Ile Lys His Ile Leu Glu Ser Leu Asp660 665 670Ser Glu Asp Gly Phe Ile Lys Glu Leu Phe Val Leu Arg Met Lys Glu675 680 685Ala Tyr Thr His Ala Gln Ile Ser Arg Asn Asn Glu Leu Lys Asp Thr690 695 700Leu Ile Leu Thr Thr Gly Asp Ile Gly Arg Ala Ala Lys Gly Asp Leu705 710 715 720Val Pro Phe Ala Leu Leu His Leu Leu His Cys Leu Leu Ser Lys Ser725 730 735Ala Ser Val Ser Gly Ala Ala Tyr Thr Glu Ile Arg Ala Leu Val Ala740 745 750Ala Lys Ser Val Lys Leu Gln Ser Phe Phe Ser Gln Tyr Lys Lys Pro755 760 765Ile Cys Gln Phe Leu Val Glu Ser Leu His Ser Ser Gln Met Thr Ala770 775 780Leu Pro Asn Thr Pro Cys Gln Asn Ala Asp Val Arg Lys Gln Asp Val785 790 795 800Ala His Gln Arg Glu Met Ala Leu Asn Thr Leu Ser Glu Ile Ala Asn805 810 815Val Phe Asp Phe Pro Asp Leu Asn Arg Phe Leu Thr Arg Thr Leu Gln820 825 830Val Leu Leu Pro Asp Leu Ala Ala Lys Ala Ser Pro Ala Ala Ser Ala835 840 845Leu Ile Arg Thr Leu Gly Lys Gln Leu Asn Val Asn Arg Arg Glu Ile850 855 860Leu Ile Asn Asn Phe Lys Tyr Ile Phe Ser His Leu Val Cys Ser Cys865 870 875 880Ser Lys Asp Glu Leu Glu Arg Ala Leu His Tyr Leu Lys Asn Glu Thr885 890 895Glu Ile Glu Leu Gly Ser Leu Leu Arg Gln Asp Phe Gln Gly Leu His900 905 910Asn Glu Leu Leu Leu Arg Ile Gly Glu His Tyr Gln Gln Val Phe Asn915 920 925Gly Leu Ser Ile Leu Ala Ser Phe Ala Ser Ser Asp Asp Pro Tyr Gln930 935 940Gly Pro Arg Asp Ile Ile Ser Pro Glu Leu Met Ala Asp Tyr Leu Gln945 950 955 960Pro Lys Leu Leu Gly Ile Leu Ala Phe Phe Asn Met Gln Leu Leu Ser965 970 975Ser Ser Val Gly Ile Glu Asp Lys Lys Met Ala Leu Asn Ser Leu Met980 985 990Ser Leu Met Lys Leu Met Gly Pro Lys His Val Ser Ser Val Arg Val995 10001005Lys Met Met Thr Thr Leu Arg Thr Gly Leu Arg Phe Lys Asp Asp Phe101010151020Pro Glu Leu Cys Cys Arg Ala Trp Asp Cys Phe Val Arg Cys Leu Asp1025103010351040His Ala Cys Leu Gly Ser Leu Leu Ser His Val Ile Val Ala Leu Leu104510501055Pro Leu Ile His Ile Gln Pro Lys Glu Thr Ala Ala Ile Phe His Tyr106010651070Leu Ile Ile Glu Asn Arg Asp Ala Val Gln Asp Phe Leu His Glu Ile107510801085Tyr Phe Leu Pro Asp His Pro Glu Leu Lys Lys Ile Lys Ala Val Leu109010951100Gln Glu Tyr Arg Lys Glu Thr Ser Glu Ser Thr Asp Leu Gln Thr Thr1105111011151120Leu Gln Leu Ser Met Lys Ala Ile Gln His Glu Asn Val Asp Val Arg112511301135Ile His Ala Leu Thr Ser Leu Lys Glu Thr Leu Tyr Lys Asn Gln Glu114011451150Lys Leu Ile Lys Tyr Ala Thr Asp Ser Glu Thr Val Glu Pro Ile Ile115511601165Ser Gln Leu Val Thr Val Leu Leu Lys Gly Cys Gln Asp Ala Asn Ser117011751180Gln Ala Arg Leu Leu Cys Gly Glu Cys Leu Gly Glu Leu Gly Ala Ile1185119011951200Asp Pro Gly Arg Leu Asp Phe Ser Thr Thr Glu Thr Gln Gly Lys Asp120512101215Phe Thr Phe Val Thr Gly Val Glu Asp Ser Ser Phe Ala Tyr Gly Leu122012251230Leu Met Glu Leu Thr Arg Ala Tyr Leu Ala Tyr Ala Asp Asn Ser Arg123512401245Ala Gln Asp Ser Ala Ala Tyr Ala Ile Gln Glu Leu Leu Ser Ile Tyr125012551260Asp Cys Arg Glu Met Glu Thr Asn Gly Pro Gly His Gln Leu Trp Arg1265127012751280Arg Phe Pro Glu His Val Arg Glu Ile Leu Glu Pro His Leu Asn Thr128512901295Arg Tyr Lys Ser Ser Gln Lys Ser Thr Asp Trp Ser Gly Val Lys Lys130013051310Pro Ile Tyr Leu Ser Lys Leu Gly Ser Asn Phe Ala Glu Trp Ser Ala131513201325Ser Trp Ala Gly Tyr Leu Ile Thr Lys Val Arg His Asp Leu Ala Ser133013351340Lys Ile Phe Thr Cys Cys Ser Ile Met Met Lys His Asp Phe Lys Val1345135013551360Thr Ile Tyr Leu Leu Pro His Ile Leu Val Tyr Val Leu Leu Gly Cys136513701375Asn Gln Glu Asp Gln Gln Glu Val Tyr Ala Glu Ile Met Ala Val Leu138013851390Lys His Asp Asp Gln His Thr Ile Asn Thr Gln Asp Ile Ala Ser Asp139514001405Leu Cys Gln Leu Ser Thr Gln Thr Val Phe Ser Met Leu Asp His Leu141014151420Thr Gln Trp Ala Arg His Lys Phe Gln Ala Leu Lys Ala Glu Lys Cys1425143014351440Pro His Ser Lys Ser Asn Arg Asn Lys Val Asp Ser Met Val Ser Thr144514501455Val Asp Tyr Glu Asp Tyr Gln Ser Val Thr Arg Phe Leu Asp Leu Ile146014651470Pro Gln Asp Thr Leu Ala Val Ala Ser Phe Arg Ser Lys Ala Tyr Thr147514801485Arg Ala Val Met His Phe Glu Ser Phe Ile Thr Glu Lys Lys Gln Asn149014951500Ile Gln Glu His Leu Gly Phe Leu Gln Lys Leu Tyr Ala Ala Met His1505151015151520Glu Pro Asp Gly Val Ala Gly Val Ser Ala Ile Arg Lys Ala Glu Pro152515301535Ser Leu Lys Glu Gln Ile Leu Glu His Glu Ser Leu Gly Leu Leu Arg154015451550Asp Ala Thr Ala Cys Tyr Asp Arg Ala Ile Gln Leu Glu Pro Asp Gln155515601565Ile Ile His Tyr His Gly Val Val Lys Ser Met Leu Gly Leu Gly Gln157015751580Leu Ser Thr Val Ile Thr Gln Val Asn Gly Val His Ala Asn Arg Ser1585159015951600Glu Trp Thr Asp Glu Leu Asn Thr Tyr Arg Val Glu Ala Ala Trp Lys160516101615Leu Ser Gln Trp Asp Leu Val Glu Asn Tyr Leu Ala Ala Asp Gly Lys162016251630Ser Thr Thr Trp Ser Val Arg Leu Gly Gln Leu Leu Leu Ser Ala Lys163516401645Lys Arg Asp Ile Thr Ala Phe Tyr Asp Ser Leu Lys Leu Val Arg Ala165016551660Glu Gln Ile Val Pro Leu Ser Ala Ala Ser Phe Glu Arg Gly Ser Tyr1665167016751680Gln Arg Gly Tyr Glu Tyr Ile Val Arg Leu His Met Leu Cys Glu Leu168516901695Glu His Ser Ile Lys Pro Leu Phe Gln His Ser Pro Gly Asp Ser Ser170017051710Gln Glu Asp Ser Leu Asn Trp Val Ala Arg Leu Glu Met Thr Gln Asn171517201725Ser Tyr Arg Ala Lys Glu Pro Ile Leu Ala Leu Arg Arg Ala Leu Leu173017351740Ser Leu Asn Lys Arg Pro Asp Tyr Asn Glu Met Val Gly Glu Cys Trp1745175017551760Leu Gln Ser Ala Arg Val Ala Arg Lys Ala Gly His His Gln Thr Ala176517701775Tyr Asn Ala Leu Leu Asn Ala Gly Glu Ser Arg Leu Ala Glu Leu Tyr178017851790Val Glu Arg Ala Lys Trp Leu Trp Ser Lys Gly Asp Val His Gln Ala179518001805Leu Ile Val Leu Gln Lys Gly Val Glu Leu Cys Phe Pro Glu Asn Glu181018151820Thr Pro Pro Glu Gly Lys Asn Met Leu Ile His Gly Arg Ala Met Leu1825183018351840Leu Val Gly Arg Phe Met Glu Glu Thr Ala Asn Phe Glu Ser Asn Ala184518501855Ile Met Lys Lys Tyr Lys Asp Val Thr Ala Cys Leu Pro Glu Trp Glu186018651870Asp Gly His Phe Tyr Leu Ala Lys Tyr Tyr Asp Lys Leu Met Pro Met187518801885Val Thr Asp Asn Lys Met Glu Lys Gln Gly Asp Leu Ile Arg Tyr Ile189018951900Val Leu His Phe Gly Arg Ser Leu Gln Tyr Gly Asn Gln Phe Ile Tyr1905191019151920Gln Ser Met Pro Arg Met Leu Thr Leu Trp Leu Asp Tyr Gly Thr Lys192519301935Ala Tyr Glu Trp Glu Lys Ala Gly Arg Ser Asp Arg Val Gln Met Arg194019451950Asn Asp Leu Gly Lys Ile Asn Lys Val Ile Thr Glu His Thr Asn Tyr195519601965Leu Ala Pro Tyr Gln Phe Leu Thr Ala Phe Ser Gln Leu Ile Ser Arg197019751980Ile Cys His Ser His Asp Glu Val Phe Val Val Leu Asp Gly Asn Asn1985199019952000Ser Gln Val Phe Leu Ala Tyr Pro Gln Gln Ala Met Trp Met Met Thr200520102015Ala Val Ser Lys Ser Ser Tyr Pro Met Arg Val Asn Arg Cys Lys Glu202020252030Ile Leu Asn Lys Ala Ile His Met Lys Lys Ser Leu Glu Lys Phe Val203520402045Gly Asp Ala Thr Arg Leu Thr Asp Lys Leu Leu Glu Leu Cys Asn Lys205020552060Pro Val Glu Ile Leu Ala Ser Leu Gln Lys Pro Lys Lys Ile Ser Leu2065207020752080Lys Gly Ser Asp Gly Lys Phe Tyr Ile Met Met Cys Lys Pro Lys Asp208520902095Asp Leu Arg Lys Asp Cys Arg Leu Met Glu Phe Asn Ser Leu Ile Asn210021052110Lys Cys Leu Arg Lys Asp Ala Glu Ser Arg Arg Arg Glu Leu His Ile211521202125Arg Thr Tyr Ala Val Ile Pro Leu Asn Asp Glu Cys Gly Ile Ile Glu213021352140Trp Val Asn Asn Thr Ala Gly Leu Arg Pro Ile Leu Thr Lys Leu Tyr2145215021552160Lys Glu Lys Gly Val Tyr Met Thr Gly Lys Glu Leu Arg Gln Cys Met216521702175Leu Pro Lys Ser Ala Ala Leu Ser Glu Lys Leu Lys Val Phe Arg Glu218021852190Phe Leu Leu Pro Arg His Pro Pro Ile Phe His Glu Trp Phe Leu Arg219522002205Thr Phe Pro Asp Pro Thr Ser Trp Tyr Ser Ser Arg Ser Ala Tyr Cys221022152220Arg Ser Thr Ala Val Met Ser Met Val Gly Tyr Ile Leu Gly Leu Gly2225223022352240Asp Arg His Gly Glu Asn Ile Leu Phe Asp Ser Leu Thr Gly Glu Cys224522502255Val His Val Asp Phe Asn Cys Leu Phe Asn Lys Gly Glu Thr Phe Glu226022652270Val Pro Glu Ile Val Pro Phe Arg Leu Thr His Asn Met Val Asn Gly227522802285Met Gly Pro Met Gly Thr Glu Gly Leu Phe Arg Arg Ala Cys Glu Val229022952300Thr Met Arg Leu Met Arg Asp Gln Arg Glu Pro Leu Met Ser Val Leu2305231023152320Lys Thr Phe Leu His Asp Pro Leu Val Glu Trp Ser Lys Pro Val Lys232523302335Gly His Ser Lys Ala Pro Leu Asn Glu Thr Gly Glu Val Val Asn Glu234023452350Lys Ala Lys Thr His Val Leu Asp Ile Glu Gln Arg Leu Gln Gly Val235523602365Ile Lys Thr Arg Asn Arg Val Thr Gly Leu Pro Leu Ser Ile Glu Gly237023752380His Val His Tyr Leu Ile Gln Glu Ala Thr Asp Glu Asn Leu Leu Cys2385239023952400Gln Met Tyr Leu Gly Trp Thr Pro Tyr Met24052410(2)SEQ ID NO25的说明(i)序列特征(A)长度7502个碱基对(B)类型核苷酸(C)链型单链(D)拓扑结构线性(ii)分子类型cDNA(ix)特征(A)姓名/符号CDS(B)位置1..7440(xi)序列描述SEQ ID NO25ATG GGT CAT GCT GTG GAA TGG CCA GTG GTC ATG AGC CGA TTT TTA AGT 45Met Gly His Ala Val Glu Trp Pro Val Val Met Ser Arg Phe Leu Ser1 5 10 15CAA TTA GAT GAA CAC ATG GGA TAT TTA CAA TCA GCT CCT TTG CAG TTG 95Gln Leu Asp Glu His Met Gly Tyr Leu Gln Ser Ala Pro Leu Gln Leu20 25 30ATG AGT ATG CAA AAT TTA GAA TTT ATT GAA GTC ACT TTA TTA ATG GTT 144Met Ser Met Gln Asn Leu Glu Phe Ile Glu Val Thr Leu Leu Met Val35 40 45CTT ACT CGT ATT ATT GCA ATT GTG TTT TTT AGA AGG CAA GAA CTC TTA 152Leu Thr Arg Ile Ile Ala Ile Val Phe Phe Arg Arg Gln Glu Leu Leu50 55 60CTT TGG CAG ATA GGT TGT GTT CTG CTA GAG TAT GGT AGT CCA AAA ATT 240Leu Trp Gln Ile Gly Cys Val Leu Leu Glu Tyr Gly Ser Pro Lys Ile65 70 75 80AAA TCC CTA GCA ATT AGC TTT TTA ACA GAA CTT TTT CAG CTT GGA GGA 255Lys Ser Leu Ala Ile Ser Phe Leu Thr Glu Leu Phe Gln Leu Gly Gly85 90 95CTA CCA GCA CAA CCA GCT AGC ACT TTT TTC AGC TCA TTT TTG GAA TTA 336Leu Pro Ala Gln Pro Ala Ser Thr Phe Phe Ser Ser Phe Leu Glu Leu100 105 110TTA AAA CAC CTT GTA GAA ATG GAT ACT GAC CAA TTG AAA CTC TAT GAA 354Leu Lys His Leu Val Glu Met Asp Thr Asp Gln Leu Lys Leu Tyr Glu115 120 125GAG CCA TTA TCA AAG CTG ATA AAG ACA CTA TTT CCC TTT GAA GCA GAA 432Glu Pro Leu Ser Lys Leu Ile Lys Thr Leu Phe Pro Phe Glu Ala Glu130 135 140GCT TAT AGA AAT ATT GAA CCT GTC TAT TTA AAT ATG CTG CTG GAA AAA 480Ala Tyr Arg Asn Ile Glu Pro Val Tyr Leu Asn Met Leu Leu Glu Lys145 150 155 160CTC TGT GTC ATG TTT GAA GAC GGT GTG CTC ATG CGG CTT AAG TCT GAT 528Leu Cys Val Met Phe Glu Asp Gly Val Leu Met Arg Leu Lys Ser Asp165 170 175TTG CTA AAA GCA GCT TTG TGC CAT TTA CTG CAG TAT TTC CTT AAA TTT 576Leu Leu Lys Ala Ala Leu Cys His Leu Leu Gln Tyr Phe Leu Lys Phe180 185 190GTG CCA GCT GGG TAT GAA TCT GCT TTA CAA GTC AGG AAG GTC TAT GTG 624Val Pro Ala Gly Tyr Glu Ser Ala Leu Gln Val Arg Lys Val Tyr Val195 200 205AGA AAT ATT TGT AAA GCT CIT TTG GAT GTG CTT GGA ATT GAG GTA GAT 672Arg Asn Ile Cys Lys Ala Leu Leu Asp Val Leu Gly Ile Glu Val Asp210 215 220GCA GAG TAC TTG TTG GGC CCA CTT TAT GCA GCT TTG AAA ATG GAA AGT 720Ala Glu Tyr Leu Leu Gly Pro Leu Tyr Ala Ala Leu Lys Met Glu Ser225 230 235 240ATG GAA ATC ATT GAG GAG ATT CAA TGC CAA ACT CAA CAG GAA AAC CTC 768Met Glu Ile Ile Glu Glu Ile Gln Cys Gln Thr Gln Gln Glu Asn Leu245 250 255AGC AGT AAT AGT GAT GGA ATA TCA CCC AAA AGG CGT CGT CTC AGC TCG 816Ser Ser Asn Ser Asp Gly Ile Ser Pro Lys Arg Arg Arg Leu Ser Ser260 265 270TCT CTA AAC CCT TCT AAA AGA GCA CCA AAA CAG ACT GAG GAA ATT AAA 864Ser Leu Asn Pro Ser Lys Arg Ala Pro Lys Gln Thr Glu Glu Ile Lys275 280 285CAT GTG GAC ATG AAC CAA AAG AGC ATA TTA TGG AGT GCA CTG AAA CAG 912His Val Asp Met Asn Gln Lys Ser Ile Leu Trp Ser Ala Leu Lys Gln290 295 300AAA GCT GAA TCC CTT CAG ATT TCC CTT GAA TAC AGT GGC CTA AAG AAT 960Lys Ala Glu Ser Leu Gln Ile Ser Leu Glu Tyr Ser Gly Leu Lys Asn305 310 315 320CCT GTT ATT GAG ATG TTA GAA GGA ATT GCT GTT GTC TTA CAA CTG ACT 1008Pro Val Ile Glu Met Leu Glu Gly Ile Ala Val Val Leu Gln Leu Thr325 330 335GCT CTG TGT ACT GTT CAT TGT TCT CAT CAA AAC ATG AAC TGC CGT ACT 1056Ala Leu Cys Thr Val His Cys Ser His Gln Asn Met Asn Cys Arg Thr340 345 350TTC AAG GAC TGT CAA CAT AAA TCC AAG AAG AAA CCT TCT GTA GTG ATA 1104Phe Lys Asp Cys Gln His Lys Ser Lys Lys Lys Pro Ser Val Val Ile355 360 365ACT TGG ATG TCA TTG GAT TTT TAC ACA AAA GTG CTT AAG AGC TGT AGA 1152Thr Trp Met Ser Leu Asp Phe Tyr Thr Lys Val Leu Lys Ser Cys Arg370 375 380AGT TTG TTA GAA TCT GTT CAG AAA CTG GAC CTG GAG GCA ACC ATT GAT 1200Ser Leu Leu Glu Ser Val Gln Lys Leu Asp Leu Glu Ala Thr Ile Asp385 390 395 400AAG GTG GTG AAA ATT TAT GAT GCT TTG ATT TAT ATG CAA GTA AAC AGT 1248Lys Val Val Lys Ile Tyr Asp Ala Leu Ile Tyr Met Gln Val Asn Ser405 410 415TCA TTT GAA GAT CAT ATC CTG GAA GAT TTA TGT GGA ATG CTC TCA CTT 1296Ser Phe Glu Asp His Ile Leu Glu Asp Leu Cys Gly Met Leu Ser Leu420 425 430CCA TGG ATT TAT TCC CAT TCT GAT GAT GGC TGT TTA AAG TTG ACC ACA 1344Pro Trp Ile Tyr Ser His Ser Asp Asp Gly Cys Leu Lys Leu Thr Thr435 440 445TTT GCC GCT AAT CTT CTA ACA TTA AGC TGT AGG ATT TCA GAT AGC TAT 1392Phe Ala Ala Asn Leu Leu Thr Leu Ser Cys Arg Ile Ser Asp Ser Tyr450 455 460TCA CCA CAG GCA CAA TCA CGA TGT GTG TTT CTT CTG ACT CTG TTT CCA 1440Ser Pro Gln Ala Gln Ser Arg Cys Val Phe Leu Leu Thr Leu Phe Pro465 470 475 480AGA AGA ATA TTC CTT GAG TGG AGA ACA GCA GTT TAC AAC TGG GCC CTG 1486Arg Arg Ile Phe Leu Glu Trp Arg Thr Ala Val Tyr Asn Trp Ala Leu485 490 495CAG AGC TCC CAT GAA GTA ATC CGG GCT AGT TGT GTT AGT GGA TTT TTT 1536Gln Ser Ser His Glu Val Ile Arg Ala Ser Cys Val Ser Gly Phe Phe500 505 510ATC TTA TTG CAG CAG CAG AAT TCT TGT AAC AGA GTT CCC AAG ATT CTT 1584Ile Leu Leu Gln Gln Gln Asn Ser Cys Asn Arg Val Pro Lys Ile Leu515 520 525ATA GAT AAA GTC AAA GAT GAT TCT GAC ATT GTC AAG AAA GAA TTT GCT 1632Ile Asp Lys Val Lys Asp Asp Ser Asp Ile Val Lys Lys Glu Phe Ala530 535 540TCT ATA CTT GGT CAA CTT GTC TGT ACT CTT CAC GGC ATG TTT TAT CTG 1680Ser Ile Leu Gly Gln Leu Val Cys Thr Leu His Gly Met Phe Tyr Leu545 550 555 560ACA AGT TCT TTA ACA GAA CCT TTC TCT GAA CAC GGA CAT GTG GAC CTC 1728Thr Ser Ser Leu Thr Glu Pro Phe Ser Glu His Gly His Val Asp Leu565 570 575TTC TGT AGG AAC TTG AAA GCC ACT TCT CAA CAT GAA TGT TCA TCT TCT 1776Phe Cys Arg Asn Leu Lys Ala Thr Ser Gln His Glu Cys Ser Ser Ser580 585 590CAA CTA AAA GCT TCT GTC TGC AAG CCA TTC CTT TTC CTA CTG AAA AAA 1824Gln Leu Lys Ala Ser Val Cys Lys Pro Phe Leu Phe Leu Leu Lys Lys595 600 605AAA ATA CCT AGT CCA GTA AAA CTT GCT TTC ATA GAT AAT CTA CAT CAT 1872Lys Ile Pro Ser Pro Val Lys Leu Ala Phe Ile Asp Asn Leu His His610 615 620CTT TGT AAG CAT CTT GAT TTT AGA GAA GAT GAA ACA GAT GTA AAA GCA 1920Leu Cys Lys His Leu Asp Phe Arg Glu Asp Glu Thr Asp Val Lys Ala625 630 635 640GTT CTT GGA ACT TTA TTA AAT TTA ATG GAA GAT CCA GAC AAA GAT GTT 1968Val Leu Gly Thr Leu Leu Asn Leu Met Glu Asp Pro Asp Lys Asp Val645 650 655AGA GTG GCT TTT AGT GGA AAT ATC AAG CAC ATA TTG GAA TCC TTG GAC 2016Arg Val Ala Phe Ser Gly Asn Ile Lys His Ile Leu Glu Ser Leu Asp660 665 670TCT GAA GAT GGA TTT ATA AAG GAG CTT TTT GTC TTA AGA ATG AAG GAA 2064Ser Glu Asp Gly Phe Ile Lys Glu Leu Phe Val Leu Arg Met Lys Glu675 680 685GCA TAT ACA CAT GCC CAA ATA TCA AGA AAT AAT GAG CTG AAG GAT ACC 2112Ala Tyr Thr His Ala Gln Ile Ser Arg Asn Asn Glu Leu Lys Asp Thr690 695 700TTG ATT CTT ACA ACA GGG GAT ATT GGA AGG GCC GCA AAA GGA GAT TTG 2160Leu Ile Leu Thr Thr Gly Asp Ile Gly Arg Ala Ala Lys Gly Asp Leu705 710 715 720GTA CCA TTT GCA CTC TTA CAC TTA TTG CAT TGT TTG TTA TCC AAG TCA 2208Val Pro Phe Ala Leu Leu His Leu Leu His Cys Leu Leu Ser Lys Ser725 730 735GCA TCT GTC TCT GGA GCA GCA TAC ACA GAA ATT AGA GCT CTG GTT GCA 2256Ala Ser Val Ser Gly Ala Ala Tyr Thr Glu Ile Arg Ala Leu Val Ala740 745 750GCT AAA AGT GTT AAA CTG CAA AGT TTT TTC AGC CAG TAT AAG AAA CCC 2304Ala Lys Ser Val Lys Leu Gln Ser Phe Phe Ser Gln Tyr Lys Lys Pro755 760 765ATC TGT CAG TTT TTG GTA GAA TCC CTT CAC TCT AGT CAG ATG ACA GCA 2352Ile Cys Gln Phe Leu Val Glu Ser Leu His Ser Ser Gln Met Thr Ala770 775 780CTT CCG AAT ACT CCA TGC CAG AAT GCT GAC GTG CGA AAA CAA GAT GTG 2400Leu Pro Asn Thr Pro Cys Gln Asn Ala Asp Val Arg Lys Gln Asp Val785 790 795 800GCT CAC CAG AGA GAA ATG GCT TTA AAT ACG TTG TCT GAA ATT GCC AAC 2448Ala His Gln Arg Glu Met Ala Leu Asn Thr Leu Ser Glu Ile Ala Asn805 810 815GTT TTC GAC TTT CCT GAT CTT AAT CGT TTT CTT ACT AGG ACA TTA CAA 2496Val Phe Asp Phe Pro Asp Leu Asn Arg Phe Leu Thr Arg Thr Leu Gln820 825 830GTT CTA CTA CCT GAT CTT GCT GCC AAA GCA AGC CCT GCA GCT TCT GCT 2544Val Leu Leu Pro Asp Leu Ala Ala Lys Ala Ser Pro Ala Ala Ser Ala835 840 845CTC ATT CGA ACT TTA GGA AAA CAA TTA AAT GTC AAT CGT AGA GAG ATT 2592Leu Ile Arg Thr Leu Gly Lys Gln Leu Asn Val Asn Arg Arg Glu Ile850 855 860TTA ATA AAC AAC TTC AAA TAT ATT TTT TCT CAT TTG GTC TGT TCT TGT 2640Leu Ile Asn Asn Phe Lys Tyr Ile Phe Ser His Leu Val Cys Ser Cys865 870 875 880TCC AAA GAT GAA TTA GAA CGT GCC CTT CAT TAT CTG AAG AAT GAA ACA 2688Ser Lys Asp Glu Leu Glu Arg Ala Leu His Tyr Leu Lys Asn Glu Thr885 890 895GAA ATT GAA CTG GGG AGC CTG TTG AGA CAA GAT TTC CAA GGA TTG CAT 2736Glu Ile Glu Leu Gly Ser Leu Leu Arg Gln Asp Phe Gln Gly Leu His900 905 910AAT GAA TTA TTG CTG CGT ATT GGA GAA CAC TAT CAA CAG GTT TTT AAT 2784Asn Glu Leu Leu Leu Arg Ile Gly Glu His Tyr Gln Gln Val Phe Asn915 920 925GGT TTG TCA ATA CTT GCC TCA TTT GCA TCC AGT GAT GAT CCA TAT CAG 2832Gly Leu Ser Ile Leu Ala Ser Phe Ala Ser Ser Asp Asp Pro Tyr Gln930 935 940GGC CCG AGA GAT ATC ATA TCA CCT GAA CTG ATG GCT GAT TAT TTA CAA 2880Gly Pro Arg Asp Ile Ile Ser Pro Glu Leu Met Ala Asp Tyr Leu Gln945 950 955 960CCC AAA TTG TTG GGC ATT TTG GCT TTT TTT AAC ATG CAG TTA CTG AGC 2928Pro Lys Leu Leu Gly Ile Leu Ala Phe Phe Asn Met Gln Leu Leu Ser965 970 975TCT AGT GTT GGC ATT GAA GAT AAG AAA ATG GCC TTG AAC AGT TTG ATG 2976Ser Ser Val Gly Ile Glu Asp Lys Lys Met Ala Leu Asn Ser Leu Met980 985 990TCT TTG ATG AAG TTA ATG GGA CCC AAA CAT GTC AGT TCT GTG AGG GTG 3024Ser Leu Met Lys Leu Met Gly Pro Lys His Val Ser Ser Val Arg Val995 10001005AAG ATG ATG ACC ACA CTG AGA ACT GGC CTT CGA TTC AAG GAT GAT TTT 3072Lys Met Met Thr Thr Leu Arg Thr Gly Leu Arg Phe Lys Asp Asp Phe101010151020CCT GAA TTG TGT TGC AGA GCT TGG GAC TGC TTT GTT CGC TGC CTG GAT 3120Pro Glu Leu Cys Cys Arg Ala Trp Asp Cys Phe Val Arg Cys Leu Asp1025103010351040CAT GCT TGT CTG GGC TCC CTT CTC AGT CAT GTA ATA GTA GCT TTG TTA 3168His Ala Cys Leu Gly Ser Leu Leu Ser His Val Ile Val Ala Leu Leu104510501055CCT CTT ATA CAC ATC CAG CCT AAA GAA ACT GCA GCT ATC TTC CAC TAC 3216Pro Leu Ile His Ile Gln Pro Lys Glu Thr Ala Ala Ile Phe His Tyr106010651070CTC ATA ATT GAA AAC AGG GAT GCT GTG CAA GAT TTT CTT CAT GAA ATA 3264Leu Ile Ile Glu Asn Arg Asp Ala Val Gln Asp Phe Leu His Glu Ile107510801085TAT TTT TTA CCT GAT CAT CCA GAA TTA AAA AAG ATA AAA GCC GTT CTC 3312Tyr Phe Leu Pro Asp His Pro Glu Leu Lys Lys Ile Lys Ala Val Leu109010951100CAG GAA TAC AGA AAG GAG ACC TCT GAG AGC ACT GAT CTT CAG ACA ACT 3360Gln Glu Tyr Arg Lys Glu Thr Ser Glu Ser Thr Asp Leu Gln Thr Thr1105111011151120CTT CAG CTC TCT ATG AAG GCC ATT CAA CAT GAA AAT GTC GAT GTT CGT 3408Leu Gln Leu Ser Met Lys Ala Ile Gln His Glu Asn Val Asp Val Arg112511301135ATT CAT GCT CTT ACA AGC TTG AAG GAA ACC TTG TAT AAA AAT CAG GAA 3456Ile His Ala Leu Thr Ser Leu Lys Glu Thr Leu Tyr Lys Asn Gln Glu114011451150AAA CTG ATA AAG TAT GCA ACA GAC AGT GAA ACA GTA GAA CCT ATT ATC 3504Lys Leu Ile Lys Tyr Ala Thr Asp Ser Glu Thr Val Glu Pro Ile Ile115511601165TCA CAG TTG GTG ACA GTG CTT TTG AAA GGT TGC CAA GAT GCA AAC TCT 3552Ser Gln Leu Val Thr Val Leu Leu Lys Gly Cys Gln Asp Ala Asn Ser117011751180CAA GCT CGG TTG CTC TGT GGG GAA TGT TTA GGG GAA TTG GGG GCG ATA 3600Gln Ala Arg Leu Leu Cys Gly Glu Cys Leu Gly Glu Leu Gly Ala Ile1185119011951200GAT CCA GGT CGA TTA GAT TTC TCA ACA ACT GAA ACT CAA GGA AAA GAT 3648Asp Pro Gly Arg Leu Asp Phe Ser Thr Thr Glu Thr Gln Gly Lys Asp120512101215TTT ACA TTT GTG ACT GGA GTA GAA GAT TCA AGC TTT GCC TAT GGA TTA 3696Phe Thr Phe Val Thr Gly Val Glu Asp Ser Ser Phe Ala Tyr Gly Leu122012251230TTG ATG GAG CTA ACA AGA GCT TAC CTT GCG TAT GCT GAT AAT AGC CGA 3744Leu Met Glu Leu Thr Arg Ala Tyr Leu AAa Tyr Ala Asp Asn Ser Arg123512401245GCT CAA GAT TCA GCT GCC TAT GCC ATT CAG GAG TTG CTT TCT ATT TAT 3792Ala Gln Asp Ser Ala Ala Tyr Ala Ile Gln Glu Leu Leu Ser Ile Tyr125012551260GAC TGT AGA GAG ATG GAG ACC AAC GGC CCA GGT CAC CAA TTG TGG AGG 3840Asp Cys Arg Glu Met Glu Thr Asn Gly Pro Gly His Gln Leu Trp Arg1265127012751280AGA TTT CCT GAG CAT GTT CGG GAA ATA CTA GAA CCT CAT CTA AAT ACC 3888Arg Phe Pro Glu His Val Arg Glu Ile Leu Glu Pro His Leu Asn Thr128512901295AGA TAC AAG AGT TCT CAG AAG TCA ACC GAT TGG TCT GGA GTA AAG AAG 3936Arg Tyr Lys Ser Ser Gln Lys Ser Thr Asp Trp Ser Gly Val Lys Lys130013051310CCA ATT TAC TTA AGT AAA TTG GGT AGT AAC TTT GCA GAA TGG TCA GCA 3984Pro Ile Tyr Leu Ser Lys Leu Gly Ser Asn Phe Ala Glu Trp Ser Ala131513201325TCT TGG GCA GGT TAT CTT ATT ACA AAG GTT CGA CAT GAT CTT GCC AGT 4032Ser Trp Ala Gly Tyr Leu Ile Thr Lys Val Arg His Asp Leu Ala Ser133013351340AAA ATT TTC ACC TGC TGT AGC ATT ATG ATG AAG CAT GAT TTC AAA GTG 4080Lys Ile Phe Thr Cys Cys Ser Ile Met Met Lys His Asp Phe Lys Val1345135013551360ACC ATC TAT CTT CTT CCA CAT ATT CTG GTG TAT GTC TTA CTG GGT TGT 4128Thr Ile Tyr Leu Leu Pro His Ile Leu Val Tyr Val Leu Leu Gly Cys136513701375AAT CAA GAA GAT CAG CAG GAG GTT TAT GCA GAA ATT ATG GCA GTT CTA 4176Asn Gln Glu Asp Gln Gln Glu Val Tyr Ala Glu Ile Met Ala Val Leu138013851390AAG CAT GAC GAT CAG CAT ACC ATA AAT ACC CAA GAC ATT GCA TCT GAT 4224Lys His Asp Asp Gln His Thr Ile Asn Thr Gln Asp Ile Ala Ser Asp139514001405CTG TGT CAA CTC AGT ACA CAG ACT GTG TTC TCC ATG CTT GAC CAT CTC 4272Leu Cys Gln Leu Ser Thr Gln Thr Val Phe Ser Met Leu Asp His Leu141014151420ACA CAG TGG GCA AGG CAC AAA TTT CAG GCA CTG AAA GCT GAG AAA TGT 4320Thr Gln Trp Ala Arg His Lys Phe Gln Ala Leu Lys Ala Glu Lys Cys1425143014351440CCA CAC AGC AAA TCA AAC AGA AAT AAG GTA GAC TCA ATG GTA TCT ACT 4368Pro His Ser Lys Ser Asn Arg Asn Lys Val Asp Ser Met Val Ser Thr144514501455GTG GAT TAT GAA GAC TAT CAG AGT GTA ACC CGT TTT CTA GAC CTC ATA 4416Val Asp Tyr Glu Asp Tyr Gln Ser Val Thr Arg Phe Leu Asp Leu Ile146014651470CCC CAG GAT ACT CTG GCA GTA GCT TCC TTT CGC TCC AAA GCA TAC ACA 4464Pro Gln Asp Thr Leu Ala Val Ala Ser Phe Arg Ser Lys Ala Tyr Thr147514801485CGA GCT GTA ATG CAC TTT GAA TCA TTT ATT ACA GAA AAG AAG CAA AAT 4512Arg Ala Val Met His Phe Glu Ser Phe Ile Thr Glu Lys Lys Gln Asn149014951500ATT CAG GAA CAT CTT GGA TTT TTA CAG AAA TTG TAT GCT GCT ATG CAT 4560Ile Gln Glu His Leu Gly Phe Leu Gln Lys Leu Tyr Ala Ala Met His1505151015151520GAA CCT GAT GGA GTG GCC GGA GTC AGT GCA ATT AGA AAG GCA GAA CCA 4608Glu Pro Asp Gly Val Ala Gly Val ser Ala Ile Arg Lys Ala Glu Pro152515301535TCT CTA AAA GAA CAG ATC CTT GAA CAT GAA AGC CTT GGC TTG CTG AGG 4656Ser Leu Lys Glu Gln Ile Leu Glu His Glu Ser Leu Gly Leu Leu Arg154015451550GAT GCC ACT GCT TGT TAT GAC AGG GCT ATT CAG CTA GAA CCA GAC CAG 4704Asp Ala Thr Ala Cys Tyr Asp Arg Ala Ile Gln Leu Glu Pro Asp Gln155515601565ATC ATT CAT TAC CAT GGT GTA GTA AAG TCC ATG TTA GGT CTT GGT CAG 4752Ile Ile His Tyr His Gly Val Val Lys Ser Met Leu Gly Leu Gly Gln157015751580CTG TCT ACT GTT ATC ACT CAG GTG AAT GGA GTG CAT GCT AAC AGG TCC 4800Leu Ser Thr Val Ile Thr Gln Val Asn Gly Val His Ala Asn Arg Ser1585159015951600GAG TGG ACA GAT GAA TTA AAC ACG TAC AGA GTG GAA GCA GCT TGG AAA 4848Glu Trp Thr Asp Glu Leu Asn Thr Tyr Arg Val Glu Ala Ala Trp Lys160516101615TTG TCA CAG TGG GAT TTG GTG GAA AAC TAT TTG GCA GCA GAT GGA AAA 4896Leu Ser Gln Trp Asp Leu Val Glu Asn Tyr Leu Ala Ala Asp Gly Lys162016251630TCT ACA ACA TGG AGT GTC AGA CTG GGA CAG CTA TTA TTA TCA GCC AAA 4944Ser Thr Thr Trp Ser Val Arg Leu Gly Gln Leu Leu Leu Ser Ala Lys163516401645AAA AGA GAT ATC ACA GCT TTT TAT GAC TCA CTG AAA CTA GTG AGA GCA 4992Lys Arg Asp Ile Thr Ala Phe Tyr Asp Ser Leu Lys Leu Val Arg Ala165016551660GAA CAA ATT GTA CCT CTT TCA GeT GCA AGC TTT GAA AGA GGC TCC TAC 5040Glu Gln Ile Val Pro Leu Ser Ala Ala Ser Phe Glu Arg Gly Ser Tyr1665167016751680CAA CGA GGA TAT GAA TAT ATT GTG AGA TTG CAC ATG TTA TGT GAG TTG 5088Gln Arg Gly Tyr Glu Tyr Ile Val Arg Leu His Met Leu Cys Glu Leu168516901695GAG CAT AGC ATC AAA CCA CTT TTC CAG CAT TCT CCA GGT GAC AGT TCT 5136Glu His Ser Ile Lys Pro Leu Phe Gln His Ser Pro Gly Asp Ser Ser170017051710CAA GAA GAT TCT CTA AAC TGG GTA GCT CGA CTA GAA ATG ACC CAG AAT 5184Gln Glu Asp Ser Leu Asn Trp Val Ala Arg Leu Glu Met Thr Gln Asn171517201725TCC TAC AGA GCC AAG GAG CCT ATC CTG GCT CTC CGG AGG GCT TTA CTA 5232Ser Tyr Arg Ala Lys Glu Pro Ile Leu Ala Leu Arg Arg Ala Leu Leu173017351740AGC CTC AAC AAA AGA CCA GAT TAC AAT GAA ATG GTT GGA GAA TGC TGG 5280Ser Leu Asn Lys Arg Pro Asp Tyr Asn Glu Met Val Gly Glu Cys Trp1745175017551760CTG CAG AGT GCC AGG GTA GCT AGA AAG GCT GGT CAC CAC CAG ACA GCC 5328Leu Gln Ser Ala Arg Val Ala Arg Lys Ala Gly His His Gln Thr Ala176517701775TAC AAT GCT CTC CTT AAT GCA GGG GAA TCA CGA CTC GCT GAA CTG TAC 5376Tyr Asn Ala Leu Leu Asn Ala Gly Glu Ser Arg Leu Ala Glu Leu Tyr178017851790GTG GAA AGG GCA AAG TGG CTC TGG TCC AAG GGT GAT GTT CAC CAG GCA 5424Val Glu Arg Ala Lys Trp Leu Trp Ser Lys Gly Asp Val His Gln Ala179518001805CTA ATI GTT CTT CAA AAA GGT GTT GAA TTA TGT TTT CCT GAA AAT GAA 5472Leu Ile Val Leu Gln Lys Gly Val Glu Leu Cys Phe Pro Glu Asn Glu181018151820ACC CCA CCT GAG GGT AAG AAC ATG TTA ATC CAT GGT CGA GCT ATG CTA 5520Thr Pro Pro Glu Gly Lys Asn Met Leu Ile His Gly Arg Ala Met Leu1825183018351840CTA GTG GGC CGA TTT ATG GAA GAA ACA GCT AAC TTT GAA AGC AAT GCA 5568Leu Val Gly Arg Phe Met Glu Glu Thr Ala Asn Phe Glu Ser Asn Ala184518501855ATT ATG AAA AAA TAT AAG GAT GTG ACC GCG TGC CTG CCA GAA TGG GAG 5616Ile Met Lys Lys Tyr Lys Asp Val Thr Ala Cys Leu Pro Glu Trp Glu186018651870GAT GGG CAT TTT TAC CTT GCC AAG TAC TAT GAC AAA TTG ATG CCC ATG 5664Asp Gly His Phe Tyr Leu Ala Lys Tyr Tyr Asp Lys Leu Met Pro Met187518801885GTC ACA GAC AAC AAA ATG GAA AAG CAA GGT GAT CTC ATC CGG TAT ATA 5712Val Thr Asp Asn Lys Met Glu Lys Gln Gly Asp Leu Ile Arg Tyr Ile189018951900GTT CTT CAT TTT GGC AGA TCT CTA CAA TAT GGA AAT CAG TTC ATA TAT 5760Val Leu His Phe Gly Arg Ser Leu Gln Tyr Gly Asn Gln Phe Ile Tyr1905191019151920CAG TCA ATG CCA CGA ATG TTA ACT CTA TGG CTT GAT TAT GGT ACA AAG 5808Gln Ser Met Pro Arg Met Leu Thr Leu Trp Leu Asp Tyr Gly Thr Lys192519301935GCA TAT GAA TGG GAA AAA GCT GGC CGC TCC GAT CGT GTA CAA ATG AGG 5856Ala Tyr Glu Trp Glu Lys Ala Gly Arg Ser Asp Arg Val Gln Met Arg194019451950AAT GAT TTG GGT AAA ATA AAC AAG GTT ATC ACA GAG CAT ACA AAC TAT 5904Asn Asp Leu Gly Lys Ile Asn Lys Val Ile Thr Glu His Thr Asn Tyr195519601965TTA GCT CCA TAT CAA TTT TTG ACT GCT TTT TCA CAA TTG ATC TCT CGA 5952Leu Ala Pro Tyr Gln Phe Leu Thr Ala Phe Ser Gln Leu Ile Ser Arg197019751980ATT TGT CAT TCT CAC GAT GAA GTT TTT GTT GTG CTT GAT GGA AAT AAT 6000Ile Cys His Ser His Asp Glu Val Phe Val Val Leu Asp Gly Asn Asn1985199019952000AGC CAA GTA TTT CTA GCC TAT CCT CAA CAA GCA ATG TGG ATG ATG ACA 6048Ser Gln Val Phe Leu Ala Tyr Pro Gln Gln Ala Met Trp Met Met Thr200520102015GCT GTG TCA AAG TCA TCT TAT CCC ATG CGT GTG AAC AGA TGC AAG GAA 6096Ala Val Ser Lys Ser Ser Tyr Pro Met Arg Val Asn Arg Cys Lys Glu202020252030ATC CTC AAT AAA GCT ATT CAT ATG AAA AAA TCC TTA GAG AAG TTT GTT 6144Ile Leu Asn Lys Ala Ile His Met Lys Lys Ser Leu Glu Lys Phe Val203520402045GGA GAT GCA ACT CGC CTA ACA GAT AAG CTT CTA GAA TTG TGC AAT AAA 6192Gly Asp Ala Thr Arg Leu Thr Asp Lys Leu Leu Glu Leu Cys Asn Lys205020552060CCG GTT GAT GGA AGT AGT TCC ACA TTA AGC ATG AGC ACT CAT TTT AAA 6240Pro Val Asp Gly Ser Ser Ser Thr Leu Ser Met Ser Thr His Phe Lys2065207020752080ATG CTT AAA AAG CTG GTA GAA GAA GCA ACA TTT AGT GAA ATC CTC ATT 6288Met Leu Lys Lys Leu Val Glu Glu Ala Thr Phe Ser Glu Ile Leu Ile208520902095CCT CTA CAA TCA GTC ATG ATA CCT ACA CTT CCA TCA ATT CTG GGT ACC 6336Pro Leu Gln Ser Val Met Ile Pro Thr Leu Pro Ser Ile Leu Gly Thr210021052110CAT GCT AAC CAT GCT AGC CAT GAA CCA TTT CCT GGA CAT TGG GCC TAT 6384His Ala Asn His Ala Ser His Glu Pro Phe Pro Gly His Trp Ala Tyr211521202125ATT GCA GGG TTT GAT GAT ATG GTG GAA ATT CTT GCT TCT CTT CAG AAA 6432Ile Ala Gly Phe Asp Asp Met Val Glu Ile Leu Ala Ser Leu Gln Lys213021352140CCA AAG AAG ATT TCT TTA AAA GGC TCA GAT GGA AAG TTC TAC ATC ATG 6480Pro Lys Lys Ile Ser Leu Lys Gly Ser Asp Gly Lys Phe Tyr Ile Met2145215021552l60ATG TGT AAG CCA AAA GAT GAC CTG AGA AAG GAT TGT AGA CTA ATG GAA 6528Met Cys Lys Pro Lys Asp Asp Leu Arg Lys Asp Cys Arg Leu Met Glu216521702175TTC AAT TCC TTG ATT AAT AAG TGC TTA AGA AAA GAT GCA GAG TCT CGT 6576Phe Asn Ser Leu Ile Asn Lys Cys Leu Arg Lys Asp Ala Glu Ser Arg218021852190AGA AGA GAA CTT CAT ATT CGA ACA TAT GCA GTT ATT CCA CTA AAT GAT 6624Arg Arg Glu Leu His Ile Arg Thr Tyr Ala Val Ile Pro Leu Asn Asp219522002205GAA TCT GGG ATT ATT GAA TGG GTG AAC AAC ACT GCT GGT TTG AGA CCT 6672Glu Cys Gly Ile Ile Glu Trp Val Asn Asn Thr Ala Gly Leu Arg Pro221022152220ATT CTG ACC AAA CTA TAT AAA GAA AAG GGA GTG TAT ATG ACA GGA AAA 6720Ile Leu Thr Lys Leu Tyr Lys Glu Lys Gly Val Tyr Met Thr Gly Lys2225223022352240GAA CTT CGC CAG TGT ATG CTA CCA AAG TCA GCA GCT TTA TCT GAA AAA 6768Glu Leu Arg Gln Cys Met Leu Pro Lys Ser Ala Ala Leu Ser Glu Lys224522502255CTC AAA GTA TTC CGA GAA TTT CTC CTG CCC AGG CAT CCT CCT ATT TTT 6816Leu Lys Val Phe Arg Glu Phe Leu Leu Pro Arg His Pro Pro Ile Phe226022652270CAT GAG TGG TTT CTG AGA ACA TTC CCT GAT CCT ACA TCA TGG TAC AGT 6864His Glu Trp Phe Leu Arg Thr Phe Pro Asp Pro Thr Ser Trp Tyr Ser227522802285AGT AGA TCA GCT TAC TGC CGT TCC ACT GCA GTA ATG TCA ATG GTT GGT 6912Ser Arg Ser Ala Tyr Cys Arg Ser Thr Ala Val Met Ser Met Val Gly229022952300TAT ATT CTG GGG CTT GGA GAC CGT CAT GGT GAA AAT ATT CTC TTT GAT 6960Tyr Ile Leu Gly Leu Gly Asp Arg His Gly Glu Asn Ile Leu Phe Asp2305231023152320TCT TTG ACT GGT GAA TGC GTA CAT GTA GAT TTC AAT TGT CTT TTC AAT 7008Ser Leu Thr Gly Glu Cys Val His Val Asp Phe Asn Cys Leu Phe Asn232523302335AAG GGA GAA ACC TTT GAA GTT CCA GAA ATT GTG CCA TTT CGC CTG ACT 7056Lys Gly Glu Thr Phe Glu Val Pro Glu Ile Val Pro Phe Arg Leu Thr234023452350CAT AAT ATG GTT AAT GGA ATG GGT CCT ATG GGA ACA GAG GGT CTT TTT 7104His Asn Met Val Asn Gly Met Gly Pro Met Gly Thr Glu Gly Leu Phe235523602365CGA AGA GCA TGT GAA GTT ACA ATG AGG CTG ATG CGT GAT CAG CGA GAG 7152Arg Arg Ala Cys Glu Val Thr Met Arg Leu Met Arg Asp Gln Arg Glu237023752380CCT TTA ATG AGT GTC TTA AAG ACT TTT CTA CAT GAT CCT CTT GTG GAA 7200Pro Leu Met Ser Val Leu Lys Thr Phe Leu His Asp Pro Leu Val Glu2385239023952400TGG AGT AAA CCA GTG AAA GGG CAT TCC AAA GCG CCA CTG AAT GAA ACT 7248Trp Ser Lys Pro Val Lys Gly His Ser Lys Ala Pro Leu Asn Glu Thr240524102415GGA GAA GTT GTC AAT GAA AAG GCC AAG ACC CAT GTT CTT GAC ATT GAG 7296Gly Glu Val Val Asn Glu Lys Ala Lys Thr His Val Leu Asp Ile Glu242024252430CAG CGA CTA CAA GGT GTA ATC AAG ACT CGA AAT AGA GTG ACA GGA CTG 7344Gln Arg Leu Gln Gly Val Ile Lys Thr Arg Asn Arg Val Thr Gly Leu243524402445CCG TTA TCT ATT GAA GGA CAT GTG CAT TAC CTT ATA CAA GAA GCT ACT 7392Pro Leu Ser Ile Glu Gly His Val His Tyr Leu Ile Gln Glu Ala Thr245024552460GAT GAA AAC TTA CTA TGC CAG ATG TAT CTT GGT TGG ACT CCA TAT ATG 7440Asp Glu Asn Leu Leu Cys Gln Met Tyr Leu Gly Trp Thr Pro Tyr Met2465247024752480TGAAATGAAA TTATGTAAAA GAATATGTTA ATAATCTAAA AGTAAAAAAA AAAAAAAAAA7500AA 7502(2)SEQ ID NO26的说明(i)序列特征(A)长度2480个氨基酸(B)类型氨基酸(D)拓扑结构线性(ii)分子类型蛋白(xi)序列描述SEQ ID NO26Met Gly His Ala Val Glu Trp Pro Val Val Met Ser Arg Phe Leu Ser1 5 10 15Gln Leu Asp Glu His Met Gly Tyr Leu Gln Ser Ala Pro Leu Gln Leu20 25 30Met Ser Met Gln Asn Leu Glu Phe Ile Glu Val Thr Leu Leu Met Val35 40 45Leu Thr Arg Ile Ile Ala Ile Val Phe Phe Arg Arg Gln Glu Leu Leu50 55 60Leu Trp Gln Ile Gly Cys Val Leu Leu Glu Tyr Gly Ser Pro Lys Ile65 70 75 80Lys Ser Leu Ala Ile Ser Phe Leu Thr Glu Leu Phe Gln Leu Gly Gly85 90 95Leu Pro Ala Gln Pro Ala Ser Thr Phe Phe Ser Ser Phe Leu Glu Leu100 105 110Leu Lys His Leu Val Glu Met Asp Thr Asp Gln Leu Lys Leu Tyr Glu115 120 125Glu Pro Leu Ser Lys Leu Ile Lys Thr Leu Phe Pro Phe Glu Ala Glu130 135 140Ala Tyr Arg Asn Ile Glu Pro Val Tyr Leu Asn Met Leu Leu Glu Lys145 150 155 160Leu Cys Val Met Phe Glu Asp Gly Val Leu Met Arg Leu Lys Ser Asp165 170 175Leu Leu Lys Ala Ala Leu Cys His Leu Leu Gln Tyr Phe Leu Lys Phe180 185 190Val Pro Ala Gly Tyr Glu Ser Ala Leu Gln Val Arg Lys Val Tyr Val195 200 205Arg Asn Ile Cys Lys Ala Leu Leu Asp Val Leu Gly Ile Glu Val Asp210 215 220Ala Glu Tyr Leu Leu Gly Pro Leu Tyr Ala Ala Leu Lys Met Glu Ser225 230 235 240Met Glu Ile Ile Glu Glu Ile Gln Cys Gln Thr Gln Gln Glu Asn Leu245 250 255Ser Ser Asn Ser Asp Gly Ile Ser Pro Lys Arg Arg Arg Leu Ser Ser260 265 270Ser Leu Asn Pro Ser Lys Arg Ala Pro Lys Gln Thr Glu Glu Ile Lys275 280 285His Val Asp Met Asn Gln Lys Ser Ile Leu Trp Ser Ala Leu Lys Gln290 295 300Lys Ala Glu Ser Leu Gln Ile Ser Leu Glu Tyr Ser Gly Leu Lys Asn305 310 315 320Pro Val Ile Glu Met Leu Glu Gly Ile Ala Val Val Leu Gln Leu Thr325 330 335Ala Leu Cys Thr Val His Cys Ser His Gln Asn Met Asn Cys Arg Thr340 345 350Phe Lys Asp Cys Gln His Lys Ser Lys Lys Lys Pro Ser Val Val Ile355360 365Thr Trp Met Ser Leu Asp Phe Tyr Thr Lys Val Leu Lys Ser Cys Arg370 375 380Ser Leu Leu Glu Ser Val Gln Lys Leu Asp Leu Glu Ala Thr Ile Asp385 390 395 400Lys Val Val Lys Ile Tyr Asp Ala Leu Ile Tyr Met Gln Val Asn Ser405 410 415Ser Phe Glu Asp His Ile Leu Glu Asp Leu Cys Gly Met Leu Ser Leu420 425 430Pro Trp Ile Tyr Ser His Ser Asp Asp Gly Cys Leu Lys Leu Thr Thr435 440 445Phe Ala Ala Asn Leu Leu Thr Leu Ser Cys Arg Ile Ser Asp Ser Tyr450 455 460Ser Pro Gln Ala Gln Ser Arg Cys Val Phe Leu Leu Thr Leu Phe Pro465 470 475 480Arg Arg Ile Phe Leu Glu Trp Arg Thr Ala Val Tyr Asn Trp Ala Leu485 490 495Gln Ser Ser His Glu Val Ile Arg Ala Ser Cys Val Ser Gly Phe Phe500 505 510Ile Leu Leu Gln Gln Gln Asn Ser Cys Asn Arg Val Pro Lys Ile Leu515 520 525Ile Asp Lys Val Lys Asp Asp Ser Asp Ile Val Lys Lys Glu Phe Ala530 535 540Ser Ile Leu Gly Gln Leu Val Cys Thr Leu His Gly Met Phe Tyr Leu545 550 555 560Thr Ser Ser Leu Thr Glu Pro Phe Ser Glu His Gly His Val Asp Leu565 570 575Phe Cys Arg Asn Leu Lys Ala Thr Ser Gln His Glu Cys Ser Ser Ser580 585 590Gln Leu Lys Ala Ser Val Cys Lys Pro Phe Leu Phe Leu Leu Lys Lys595 600 605Lys Ile Pro Ser Pro Val Lys Leu Ala Phe Ile Asp Asn Leu His His610 615 620Leu Cys Lys His Leu Asp Phe Arg Glu Asp Glu Thr Asp Val Lys Ala625 630 635 640Val Leu Gly Thr Leu Leu Asn Leu Met Glu Asp Pro Asp Lys Asp Val645 650 655Arg Val Ala Phe Ser Gly Asn Ile Lys His Ile Leu Glu Ser Leu Asp660 665 670Ser Glu Asp Gly Phe Ile Lys Glu Leu Phe Val Leu Arg Met Lys Glu675 680 685Ala Tyr Thr His Ala Gln Ile Ser Arg Asn Asn Glu Leu Lys Asp Thr690 695 700Leu Ile Leu Thr Thr Gly Asp Ile Gly Arg Ala Ala Lys Gly Asp Leu705 710 715 720Val Pro Phe Ala Leu Leu His Leu Leu His Cys Leu Leu Ser Lys Ser725 730 735Ala Ser Val Ser Gly Ala Ala Tyr Thr Glu Ile Arg Ala Leu Val Ala740 745 750Ala Lys Ser Val Lys Leu Gln Ser Phe Phe Ser Gln Tyr Lys Lys Pro755 760 765Ile Cys Gln Phe Leu Val Glu Ser Leu His Ser Ser Gln Met Thr Ala770 775 780Leu Pro Asn Thr Pro Cys Gln Asn Ala Asp Val Arg Lys Gln Asp Val785 790 795 800Ala His Gln Arg Glu Met Ala Leu Asn Thr Leu Ser Glu Ile Ala Asn805 810 815Val Phe Asp Phe Pro Asp Leu Asn Arg Phe Leu Thr Arg Thr Leu Gln820 825 830Val Leu Leu Pro Asp Leu Ala Ala Lys Ala Ser Pro Ala Ala Ser Ala835 840 845Leu Ile Arg Thr Leu Gly Lys Gln Leu Asn Val Asn Arg Arg Glu Ile850 855 860Leu Ile Asn Asn Phe Lys Tyr Ile Phe Ser His Leu Val Cys Ser Cys865 870 875 880Ser Lys Asp Glu Leu Glu Arg Ala Leu His Tyr Leu Lys Asn Glu Thr885 890 895Glu Ile Glu Leu Gly Ser Leu Leu Arg Gln Asp Phe Gln Gly Leu His900 905 910Asn Glu Leu Leu Leu Arg Ile Gly Glu His Tyr Gln Gln Val Phe Asn915 920 925Gly Leu Ser Ile Leu Ala Ser Phe Ala Ser Ser Asp Asp Pro Tyr Gln930 935 940Gly Pro Arg Asp Ile Ile Ser Pro Glu Leu Met Ala Asp Tyr Leu Gln945 950 955 960Pro Lys Leu Leu Gly Ile Leu Ala Phe Phe Asn Met Gln Leu Leu Ser965 970 975Ser Ser Val Gly Ile Glu Asp Lys Lys Met Ala Leu Asn Ser Leu Met980 985 990Ser Leu Met Lys Leu Met Gly Pro Lys His Val Ser Ser Val Arg Val995 10001005Lys Met Met Thr Thr Leu Arg Thr Gly Leu Arg Phe Lys Asp Asp Phe101010151020Pro Glu Leu Cys Cys Arg Ala Trp Asp Cys Phe Val Arg Cys Leu Asp1025103010351040His Ala Cys Leu Gly Ser Leu Leu Ser His Val Ile Val Ala Leu Leu104510501055Pro Leu Ile His Ile Gln Pro Lys Glu Thr Ala Ala Ile Phe His Tyr106010651070Leu Ile Ile Glu Asn Arg Asp Ala Val Gln Asp Phe Leu His Glu Ile107510801085Tyr Phe Leu Pro Asp His Pro Glu Leu Lys Lys Ile Lys Ala Val Leu109010951100Gln Glu Tyr Arg Lys Glu Thr Ser Glu Ser Thr Asp Leu Gln Thr Thr1105111011151120Leu Gln Leu Ser Met Lys Ala Ile Gln His Glu Asn Val Asp Val Arg112511301135Ile His Ala Leu Thr Ser Leu Lys Glu Thr Leu Tyr Lys Asn Gln Glu114011451150Lys Leu Ile Lys Tyr Ala Thr Asp Ser Glu Thr Val Glu Pro Ile Ile115511601165Ser Gln Leu Val Thr Val Leu Leu Lys Gly Cys Gln Asp Ala Asn Ser117011751180Gln Ala Arg Leu Leu Cys Gly Glu Cys Leu Gly Glu Leu Gly Ala Ile1185119011951200Asp Pro Gly Arg Leu Asp Phe Ser Thr Thr Glu Thr Gln Gly Lys Asp120512101215Phe Thr Phe Val Thr Gly Val Glu Asp Ser Ser Phe Ala Tyr Gly Leu122012251230Leu Met Glu Leu Thr Arg Ala Tyr Leu Ala Tyr Ala Asp Asn Ser Arg123512401245Ala Gln Asp Ser Ala Ala Tyr Ala Ile Gln Glu Leu Leu Ser Ile Tyr125012551260Asp Cys Arg Glu Met Glu Thr Asn Gly Pro Gly His Gln Leu Trp Arg1265127012751280Arg Phe Pro Glu His Val Arg Glu Ile Leu Glu Pro His Leu Asn Thr128512901295Arg Tyr Lys Ser Ser Gln Lys Ser Thr Asp Trp Ser Gly Val Lys Lys130013051310Pro Ile Tyr Leu Ser Lys Leu Gly Ser Asn Phe Ala Glu Trp Ser Ala131513201325Ser Trp Ala Gly Tyr Leu Ile Thr Lys Val Arg His Asp Leu Ala Ser133013351340Lys Ile Phe Thr Cys Cys Ser Ile Met Met Lys His Asp Phe Lys Val1345135013551360Thr Ile Tyr Leu Leu Pro His Ile Leu Val Tyr Val Leu Leu Gly Cys136513701375Asn Gln Glu Asp Gln Gln Glu Val Tyr Ala Glu Ile Met Ala Val Leu138013851390Lys His Asp Asp Gln His Thr Ile Asn Thr Gln Asp Ile Ala Ser Asp139514001405Leu Cys Gln Leu Ser Thr Gln Thr Val Phe Ser Met Leu Asp His Leu14101415 1420Thr Gln Trp Ala Arg His Lys Phe Gln Ala Leu Lys Ala Glu Lys Cys1425143014351440Pro His Ser Lys Ser Asn Arg Asn Lys Val Asp Ser Met Val Ser Thr144514501455Val Asp Tyr Glu Asp Tyr Gln Ser Val Thr Arg Phe Leu Asp Leu Ile146014651470Pro Gln Asp Thr Leu Ala Val Ala Ser Phe Arg Ser Lys Ala Tyr Thr147514801485Arg Ala Val Met His Phe Glu Ser Phe Ile Thr Glu Lys Lys Gln Asn149014951500Ile Gln Glu His Leu Gly Phe Leu Gln Lys Leu Tyr Ala Ala Met His1505151015151520Glu Pro Asp Gly Val Ala Gly Val Ser Ala Ile Arg Lys Ala Glu Pro152515301535Ser Leu Lys Glu Gln Ile Leu Glu His Glu Ser Leu Gly Leu Leu Arg154015451550Asp Ala Thr Ala Cys Tyr Asp Arg Ala Ile Gln Leu Glu Pro Asp Gln155515601565Ile Ile His Tyr His Gly Val Val Lys Ser Met Leu Gly Leu Gly Gln157015751580Leu Ser Thr Val Ile Thr Gln Val Asn Gly Val His Ala Asn Arg Ser1585159015951600Glu Trp Thr Asp Glu Leu Asn Thr Tyr Arg Val Glu Ala Ala Trp Lys160516101615Leu Ser Gln Trp Asp Leu Val Glu Asn Tyr Leu Ala Ala Asp Gly Lys162016251630Ser Thr Thr Trp Ser Val Arg Leu Gly Gln Leu Leu Leu Ser Ala Lys163516401645Lys Arg Asp Ile Thr Ala Phe Tyr Asp Ser Leu Lys Leu Val Arg Ala165016551660Glu Gln Ile Val Pro Leu Ser Ala Ala Ser Phe Glu Arg Gly Ser Tyr1665167016751680Gln Arg Gly Tyr Glu Tyr Ile Val Arg Leu His Met Leu Cys Glu Leu168516901695Glu His Ser Ile Lys Pro Leu Phe Gln His Ser Pro Gly Asp Ser Ser170017051710Gln Glu Asp Ser Leu Asn Trp Val Ala Arg Leu Glu Met Thr Gln Asn171517201725Ser Tyr Arg Ala Lys Glu Pro Ile Leu Ala Leu Arg Arg Ala Leu Leu173017351740Ser Leu Asn Lys Arg Pro Asp Tyr Asn Glu Met Val Gly Glu Cys Trp1745175017551760Leu Gln Ser Ala Arg Val Ala Arg Lys Ala Gly His His Gln Thr Ala176517701775Tyr Asn Ala Leu Leu Asn Ala Gly Glu Ser Arg Leu Ala Glu Leu Tyr178017851790Val Glu Arg Ala Lys Trp Leu Trp Ser Lys Gly Asp Val His Gln Ala179518001805Leu Ile Val Leu Gln Lys Gly Val Glu Leu Cys Phe Pro Glu Asn Glu181018151820Thr Pro Pro Glu Gly Lys Asn Met Leu Ile His Gly Arg Ala Met Leu1825183018351840Leu Val Gly Arg Phe Met Glu Glu Thr Ala Asn Phe Glu Ser Asn Ala184518501855Ile Met Lys Lys Tyr Lys Asp Val Thr Ala Cys Leu Pro Glu Trp Glu186018651870Asp Gly His Phe Tyr Leu Ala Lys Tyr Tyr Asp Lys Leu Met Pro Met187518801885Val Thr Asp Asn Lys Met Glu Lys Gln Gly Asp Leu Ile Arg Tyr Ile189018951900Val Leu His Phe Gly Arg Ser Leu Gln Tyr Gly Asn Gln Phe Ile Tyr1905191019151920Gln Ser Met Pro Arg Met Leu Thr Leu Trp Leu Asp Tyr Gly Thr Lys192519301935Ala Tyr Glu Trp Glu Lys Ala Gly Arg Ser Asp Arg Val Gln Met Arg194019451950Asn Asp Leu Gly Lys Ile Asn Lys Val Ile Thr Glu His Thr Asn Tyr195519601965Leu Ala Pro Tyr Gln Phe Leu Thr Ala Phe Ser Gln Leu Ile Ser Arg197019751980Ile Cys His Ser His Asp Glu Val Phe Val Val Leu Asp Gly Asn Asn1985199019952000Ser Gln Val Phe Leu Ala Tyr Pro Gln Gln Ala Met Trp Met Met Thr200520102015Ala Val Ser Lys Ser Ser Tyr Pro Met Arg Val Asn Arg Cys Lys Glu202020252030Ile Leu Asn Lys Ala Ile His Met Lys Lys Ser Leu Glu Lys Phe Val203520402045Gly Asp Ala Thr Arg Leu Thr Asp Lys Leu Leu Glu Leu Cys Asn Lys205020552060Pro Val Asp Gly Ser Ser Ser Thr Leu Ser Met Ser Thr His Phe Lys2065207020752080Met Leu Lys Lys Leu Val Glu Glu Ala Thr Phe Ser Glu Ile Leu Ile208520902095Pro Leu Gln Ser Val Met Ile Pro Thr Leu Pro Ser Ile Leu Gly Thr210021052110His Ala Asn His Ala Ser His Glu Pro Phe Pro Gly His Trp Ala Tyr211521202125Ile Ala Gly Phe Asp Asp Met Val Glu Ile Leu Ala Ser Leu Gln Lys213021352140Pro Lys Lys Ile Ser Leu Lys Gly Ser Asp Gly Lys Phe Tyr Ile Met2145215021552160Met Cys Lys Pro Lys Asp Asp Leu Arg Lys Asp Cys Arg Leu Met Glu216521702175Phe Asn Ser Leu Ile Asn Lys Cys Leu Arg Lys Asp Ala Glu Ser Arg218021852190Arg Arg Glu Leu His Ile Arg Thr Tyr Ala Val Ile Pro Leu Asn Asp219522002205Glu Cys Gly Ile Ile Glu Trp Val Asn Asn Thr Ala Gly Leu Arg Pro221022152220Ile Leu Thr Lys Leu Tyr Lys Glu Lys Gly Val Tyr Met Thr Gly Lys2225223022352240Glu Leu Arg Gln Cys Met Leu Pro Lys Ser Ala Ala Leu Ser Glu Lys224522502255Leu Lys Val Phe Arg Glu Phe Leu Leu Pro Arg His Pro Pro Ile Phe226022652270His Glu Trp Phe Leu Arg Thr Phe Pro Asp Pro Thr Ser Trp Tyr Ser227522802285Ser Arg Ser Ala Tyr Cys Arg Ser Thr Ala Val Met Ser Met Val Gly229022952300Tyr Ile Leu Gly Leu Gly Asp Arg His Gly Glu Asn Ile Leu Phe Asp2305231023152320Ser Leu Thr Gly Glu Cys Val His Val Asp Phe Asn Cys Leu Phe Asn232523302335Lys Gly Glu Thr Phe Glu Val Pro Glu Ile Val Pro Phe Arg Leu Thr234023452350His Asn Met Val Asn Gly Met Gly Pro Met Gly Thr Glu Gly Leu Phe235523602365Arg Arg Ala Cys Glu Val Thr Met Arg Leu Met Arg Asp Gln Arg Glu237023752380Pro Leu Met Ser Val Leu Lys Thr Phe Leu His Asp Pro Leu Val Glu2385239023952400Trp Ser Lys Pro Val Lys Gly His Ser Lys Ala Pro Leu Asn Glu Thr240524102415Gly Glu Val Val Asn Glu Lys Ala Lys Thr His Val Leu Asp Ile Glu242024252430Gln Arg Leu Gln Gly Val Ile Lys Thr Arg Asn Arg Val Thr Gly Leu243524402445Pro Leu Ser Ile Glu Gly His Val His Tyr Leu Ile Gln Glu Ala Thr245024552460Asp Glu Asn Leu Leu Cys Gln Met Tyr Leu Gly Trp Thr Pro Tyr Met2465247024752480(2)SEQ ID NO27的说明(i)序列特征(A)长度878个碱基对(B)类型核苷酸(C)链型单链(D)拓扑结构线性(ii)分子类型DNA(xi)序列描述SEQ ID NO27ATCCATTGTG TTGGAAAGGA ATGATGAATG TGGGATTATT GAATGGGTGA ACAATACTGC 60TGGCTTGAGA CCTATTCTGA CCAAAATATA TAAAGAAAAG GGAGTGTATA TGACAGGAAA 120GGAGCTTCGC CAGTGTATGC TACCAAAGTC AGCAGCTTTA TCTGAAAAAC TCAAAGTATT 180CCAAGAATTA CTCCTGCCCA GGCATCCTCC TGTTTTTCAT GAGTGGTTTC TGAGAACATT 240CCCTGATCCT ACATCATGGT ACAGTAGCAG ATCTGCATAT TGCCGCTCTA CTGCAGTCAT 300GTCAATGGTT GGCTACATCC TGGGGCTTGG AGACCGTCAT GGTGAAAACA TTCTTTTTGA 360CTCTTTCACT GGTGAATGTG TACATGTAGA TTTCAACTGT CTTTTTAATA AGGGAGAAAC 420GTTTGAAGTT CCGGAAATTG TACCATTTCG ACTGACTCAT AATATGGTTA ATGGAATGGG 480TCCTATGGGA ACAGAGGGTC TATTTCGAAG AGCATGTGAA GTTACACTGA GACTGATGAG 540GGATCAGAGA GAACCTTTAA TGAGTGTCTT AAAGACTTTT CTACACGATC CTCTAGTGGA 600GTGGAGTAAA CCAGTGAAAG GACACTCCAA AGCACCACTG AATGAAACCG GGGAAGTTGT 660CAATGAGAAG GCCAAGACCC ATGTTCTTGA CATTGAACAA CGACTACAAG GTGTGATCAA 720AACCCGAAAT AGAGTAACAG GGCTGCCATT ATCTATTGAA GGACATGTGC ATTACCTCAT 780ACAAGAAGCT ACTGATGAAA ACTTACTCTG TCAGATGTAC CTTGGTTGGA CCCCATATAT 840GTAAAATAAA ATTATTTCAA AGAAAAAAAA AAAAAAAA 878(2)SEQ ID NO28的说明(i)序列特征(A)长度7935个碱基对(B)类型核苷酸(C)链型单链(D)拓扑结构线性(ii)分子类型cDNA(ix)特征(A)姓名/符号CDS(B)位置1..7932(xi)序列描述SEQ ID NO28ATG GGG GAA CAT GGC CTG GAG CTG GCT TCC ATG ATC CCC GCC CTG CGG 48Met Gly Glu His Gly Leu Glu Leu Ala Ser Met Ile Pro Ala Leu Arg1 5 10 15GAG CTG GGC AGT GCC ACA CCA GAG GAA TAT AAT ACA GTT GTA GAG AAG 96Glu Leu Gly Ser Ala Thr Pro Glu Glu Tyr Asn Thr Val Val Gln Lys20 25 30CCA AGA CAA ATT CTG TGT CAA TTC ATT GAC CGG ATA CTT ACA GAT GTA 144Pro Arg Gln Ile Leu Cys Gln Phe Ile Asp Arg Ile Leu Thr Asp Val35 40 45AAT GTT GTT GCT GTA GAA CTT GTA AAG AAA ACT GAC TCT CAG CCA ACC 192Asn Val Val Ala Val Glu Leu Val Lys Lys Thr Asp Ser Gln Pro Thr50 55 60TCC GTG ATG TTG CTT GAT TTC ATC CAG CAT ATC ATG AAA TCC TCC CCA 240Ser Val Met Leu Leu Asp Phe Ile Gln His Ile Met Lys Ser Ser Pro65 70 75 80CTT ATG TTT GTA AAT GTG AGT GGA AGC CAT GAG CGC AAA GGC AGT TGT 288Leu Met Phe Val Asn Val Ser Gly Ser His Glu Arg Lys Gly Ser Cys85 90 95ATT GAA TTC AGT AAT TGG ATC ATA ACG AGA CTT CTG CGG ATT GCA GCA 336Ile Glu Phe Ser Asn Trp Ile Ile Thr Arg Leu Leu Arg Ile Ala Ala100 105 110ACT CCC TCC TGT CAT TTG TTA CAC AAG AAA ATC TGT GAA GTC ATC TGT 384Thr Pro Ser Cys His Leu Leu His Lys Lys Ile Cys Glu Val Ile Cys115 120 125TCA TTA TTA TTT CTT TTT AAA AGC AAG AGT CCT GCT ATT TTT GGG GTA 432Ser Leu Leu Phe Leu Phe Lys Ser Lys Ser Pro Ala Ile Phe Gly Val130 135 140CTC ACA AAA GAA TTA TTA CAA CTT TTT GAA GAC TTG GTT TAC CTC CAT 480Leu Thr Lys Glu Leu Leu Gln Leu Phe Glu Asp Leu Val Tyr Leu His145 150 155 160AGA AGA AAT GTG ATG GGT CAT GCT GTG GAA TGG CCA GTG GTC ATG AGC 528Arg Arg Asn Val Met Gly His Ala Val Glu Trp Pro Val Val Met Ser165 170 175CGA TTT TTA AGT CAA TTA GAT GAA CAC ATG GGA TAT TTA CAA TCA GCT 576Arg Phe Leu Ser Gln Leu Asp Glu His Met Gly Tyr Leu Gln Ser Ala180 185 190CCT TTG CAG TTG ATG AGT ATG CAA AAT TTA GAA TTT ATT GAA GTC ACT 624Pro Leu Gln Leu Met Ser Met Gln Asn Leu Glu Phe Ile Glu Val Thr195 200 205TTA TTA ATG GTT CTT ACT CGT ATT ATT GCA A7T GTG TTT TTT AGA AGG 672Leu Leu Met Val Leu Thr Arg Ile Ile Ala Ile Val Phe Phe Arg Arg210 215 220CAA GAA CTC TTA CTT TGG CAG ATA GGT TGT GTT CTG CTA GAG TAT GGT 720Gln Glu Leu Leu Leu Trp Gln Ile Gly Cys Val Leu Leu Glu Tyr Gly225 230 235 240AGT CCA AAA ATT AAA TCC CTA GCA ATT AGC TTT TTA ACA GAA CTT TTT 768Ser Pro Lys Ile Lys Ser Leu Ala Ile Ser Phe Leu Thr Glu Leu Phe245 250 255CAG CTT GGA GGA CTA CCA GCA CAA CCA GCT AGC ACT TTT TTC AGC TCA 816Gln Leu Gly Gly Leu Pro Ala Gln Pro Ala Ser Thr Phe Phe Ser Ser260 265 270TTT TTG GAA TTA TTA AAA CAC CTT GTA GAA ATG GAT ACT GAC CAA TTG 864Phe Leu Glu Leu Leu Lys His Leu Val Glu Met Asp Thr Asp Gln Leu275 280 285AAA CTC TAT GAA GAG CCA TTA TCA AAG CTG ATA AAG ACA CTA TTT CCC 912Lys Leu Tyr Glu Glu Pro Leu Ser Lys Leu Ile Lys Thr Leu Phe Pro290 295 300TTT GAA GCA GAA GCT TAT AGA AAT ATT GAA CCT GTC TAT TTA AAT ATG 960Phe Glu Ala Glu Ala Tyr Arg Asn Ile Glu Pro Val Tyr Leu Asn Met305 310 315 320CTG CTG GAA AAA CTC TGT GTC ATG TTT GAA GAC GGT GTG CTC ATG CGG 1008Leu Leu Glu Lys Leu Cys Val Met Phe Glu Asp Gly Val Leu Met Arg325 330 335CTT AAG TCT GAT TTG CTA AAA GCA GCT TTG TGC CAT TTA CTG CAG TAT 1056Leu Lys Ser Asp Leu Leu Lys Ala Ala Leu Cys His Leu Leu Gln Tyr340 345 350TTC CTT AAA TTT GTG CCA GCT GGG TAT GAA TCT GCT TTA CAA GTC AGG 1104Phe Leu Lys Phe Val Pro Ala Gly Tyr Glu Ser Ala Leu Gln Val Arg355 360 365AAG GTC TAT GTG AGA AAT ATT TGT AAA GCT CTT TTG GAT GTG CTT GGA 1152Lys Val Tyr Val Arg Asn Ile Cys Lys Ala Leu Leu Asp Val Leu Gly370 375 380ATT GAG GTA GAT GCA GAG TAC TTG TTG GGC CCA CTT TAT GCA GCT TTG 1200Ile Glu Val Asp Ala Glu Tyr Leu Leu Gly Pro Leu Tyr Ala Ala Leu385 390 395 400AAA ATG GAA AGT ATG GAA ATC ATT GAG GAG ATT CAA TGC CAA ACT CAA 1248Lys Met Glu Ser Met Glu Ile Ile Glu Glu Ile Gln Cys Gln Thr Gln405 410 415CAG GAA AAC CTC AGC AGT AAT AGT GAT GGA ATA TCA CCC AAA AGG CGT 1296Gln Glu Asn Leu Ser Ser Asn Ser Asp Gly Ile Ser Pro Lys Arg Arg420 425 430CGT CTC AGC TCG TCT CTA AAC CCT TCT AAA AGA GCA CCA AAA CAG ACT 1344Arg Leu Ser Ser Ser Leu Asn Pro Ser Lys Arg Ala Pro Lys Gln Thr435 440 445GAG GAA ATT AAA CAT GTG GAC ATG AAC CAA AAG AGC ATA TTA TGG AGT 1392Glu Glu Ile Lys His Val Asp Met Asn Gln Lys Ser Ile Leu Trp Ser450 455 460GCA CTG AAA CAG AAA GCT GAA TCC CTT CAG ATT TCC CTT GAA TAC AGT 1440Ala Leu Lys Gln Lys Ala Glu Ser Leu Gln Ile Ser Leu Glu Tyr Ser465 470 475 480GGC CTA AAG AAT CCT GTT ATT GAG ATG TTA GAA GGA ATT GCT GTT GTC 1488Gly Leu Lys Asn Pro Val Ile Glu Met Leu Glu Gly Ile Ala Val Val485 490 495TTA CAA CTG ACT GCT CTG TGT ACT GTT CAT TGT TCT CAT CAA AAC ATG 1536Leu Gln Leu Thr Ala Leu Cys Thr Val His Cys Ser His Gln Asn Met500 505 510AAC TGC CGT ACT TTC AAG GAC TGT CAA CAT AAA TCC AAG AAG AAA CCT 1584Asn Cys Arg Thr Phe Lys Asp Cys Gln His Lys Ser Lys Lys Lys Pro515 520 525TCT GTA GTG ATA ACT TGG ATG TCA TTG GAT TTT TAC ACA AAA GTG CTT 1632Ser Val Val Ile Thr Trp Met Ser Leu Asp Phe Tyr Thr Lys Val Leu530 535 540AAG AGC TGT AGA AGT TTG TTA GAA TCT GTT CAG AAA CTG GAC CTG GAG 1680Lys Ser Cys Arg Ser Leu Leu Glu Ser Val Gln Lys Leu Asp Leu Glu545 550 555 560GCA ACC ATT GAT AAG GTG GTG AAA ATT TAT GAT GCT TTG ATT TAT ATG 1728Ala Thr Ile Asp Lys Val Val Lys Ile Tyr Asp Ala Leu Ile Tyr Met565 570 575CAA GTA AAC AGT TCA TTT GAA GAT CAT ATC CTG GAA GAT TTA TGT GGT 1776Gln Val Asn Ser Ser Phe Glu Asp His Ile Leu Glu Asp Leu Cys Gly580 585 590ATG CTC TCA CTT CCA TGG ATT TAT TCC CAT TCT GAT GAT GGC TGT TTA 1824Met Leu Ser Leu Pro Trp Ile Tyr Ser His Ser Asp Asp Gly Cys Leu595 600 605AAG TTG ACC ACA TTT GCC GCT AAT CTT CTA ACA TTA AGC TGT AGG ATT 1872Lys Leu Thr Thr Phe Ala Ala Asn Leu Leu Thr Leu Ser Cys Arg Ile610 615 620TCA GAT AGC TAT TCA CCA CAG GCA CAA TCA CGA TGT GTG TTT CTT CTG 1920Ser Asp Ser Tyr Ser Pro Gln Ala Gln Ser Arg Cys Val Phe Leu Leu625 630 635 640ACT CTG TTT CCA AGA AGA ATA TTC CTT GAG TGG AGA ACA GCA GTT TAC 1968Thr Leu Phe Pro Arg Arg Ile Phe Leu Glu Trp Arg Thr Ala Val Tyr645 650 655AAC TGG GCC CTG CAG AGC TCC CAT GAA GTA ATC CGG GCT AGT TGT GTT 2016Asn Trp Ala Leu Gln Ser Ser His Glu Val Ile Arg Ala Ser Cys Val660 665 670AGT GGA TTT TTT ATC TTA TTG CAG CAG CAG AAT TCT TGT AAC AGA GTT 2064Ser Gly Phe Phe Ile Leu Leu Gln Gln Gln Asn Ser Cys Asn Arg Val675 680 685CCC AAG ATT CTT ATA GAT AAA GTC AAA GAT GAT TCT GAC ATT GTC AAG 2112Pro Lys Ile Leu Ile Asp Lys Val Lys Asp Asp Ser Asp Ile Val Lys690 695 700AAA GAA TTT GCT TCT ATA CTT GGT CAA CTT GTC TGT ACT CTT CAC GGC 2160Lys Glu Phe Ala Ser Ile Leu Gly Gln Leu Val Cys Thr Leu His Gly705 710 715 720ATG TTT TAT CTG ACA AGT TCT TTA ACA GAA CCT TTC TCT GAA CAC GGA 2208Met Phe Tyr Leu Thr Ser Ser Leu Thr Glu Pro Phe Ser Glu His Gly725 730 735CAT GTG GAC CTC TTC TGT AGG AAC TTG AAA GCC ACT TCT CAA CAT GAA 2256His Val Asp Leu Phe Cys Arg Asn Leu Lys Ala Thr Ser Gln His Glu740 745 750TGT TCA TCT TCT CAA CTA AAA GCT TCT GTC TGC AAG CCA TTC CTT TTC 2304Cys Ser Ser Ser Gln Leu Lys Ala Ser Val Cys Lys Pro Phe Leu Phe755 760 765CTA CTG AAA AAA AAA ATA CCT AGT CCA GTA AAA CTT GCT TTC ATA GAT 2352Leu Leu Lys Lys Lys Ile Pro Ser Pro Val Lys Leu Ala Phe Ile Asp770 775 780AAT CTA CAT CAT CTT TGT AAG CAT CTT GAT TTT AGA GAA GAT GAA ACA 2400Asn Leu His His Leu Cys Lys His Leu Asp Phe Arg Glu Asp Glu Thr785 790 795 800GAT GTA AAA GCA GTT CTT GGA ACT TTA TTA AAT TTA ATG GAA GAT CCA 2448Asp Val Lys Ala Val Leu Gly Thr Leu Leu Asn Leu Met Glu Asp Pro805 810 815GAC AAA GAT GTT AGA GTG GCT TTT AGT GGA AAT ATC AAG CAC ATA TTG 2496Asp Lys Asp Val Arg Val Ala Phe Ser Gly Asn Ile Lys His Ile Leu820 825 830GAA TCC TTG GAC TCT GAA GAT GGA TTT ATA AAG GAG CTT TTT GTC TTA 2544Glu Ser Leu Asp Ser Glu Asp Gly Phe Ile Lys Glu Leu Phe Val Leu835 840 845AGA ATG AAG GAA GCA TAT ACA CAT GCC CAA ATA TCA AGA AAT AAT GAG 2592Arg Met Lys Glu Ala Tyr Thr His Ala Gln Ile Ser Arg Asn Asn Glu850 855 860CTG AAG GAT ACC TTG ATT CTT ACA ACA GGG GAT ATT GGA AGG GCC GCA 2640Leu Lys Asp Thr Leu Ile Leu Thr Thr Gly Asp Ile Gly Arg Ala Ala865 870 875 880AAA GGA GAT TTG GTA CCA TTT GCA CTC TTA CAC TTA TTG CAT TGT TTG 2688Lys Gly Asp Leu Val Pro Phe Ala Leu Leu His Leu Leu His Cys Leu885 890 895TTA TCC AAG TCA GCA TCT GTC TCT GGA GCA GCA TAC ACA GAA ATT AGA 2736Leu Ser Lys Ser Ala Ser Val Ser Gly Ala Ala Tyr Thr Glu Ile Arg900 905 910GCT CTG GTT GCA GCT AAA AGT GTT AAA CTG CAA AGT TTT TTC AGC CAG 2784Ala Leu Val Ala Ala Lys Ser Val Lys Leu Gln Ser Phe Phe Ser Gln915 920 925TAT AAG AAA CCC ATC TGT CAG TTT TTG GTA GAA TCC CTT CAC TCT AGT 2832Tyr Lys Lys Pro Ile Cys Gln Phe Leu Val Glu Ser Leu His Ser Ser930 935 940CAG ATG ACA GCA CTT CCG AAT ACT CCA TGC CAG AAT GCT GAC GTG CGA 2880Gln Met Thr Ala Leu Pro Asn Thr Pro Cys Gln Asn Ala Asp Val Arg945 950 955 960AAA CAA GAT GTG GCT CAC CAG AGA GAA ATG GCT TTA AAT ACG TTG TCT 2928Lys Gln Asp Val Ala His Gln Arg Glu Met Ala Leu Asn Thr Leu Ser965 970 975GAA ATT GCC AAC GTT TTC GAC TTT CCT GAT CTT AAT CGT TTT CTT ACT 2976Glu Ile Ala Asn Val Phe Asp Phe Pro Asp Leu Asn Arg Phe Leu Thr980 985 990AGG ACA TTA CAA GTT CTA CTA CCT GAT CTT GCT GCC AAA GCA AGC CCT 3024Arg Thr Leu Gln Val Leu Leu Pro Asp Leu Ala Ala Lys Ala Ser Pro995 10001005GCA GCT TCT GCT CTC ATT CGA ACT TTA GGA AAA CAA TTA AAT GTC AAT 3072Ala Ala Ser Ala Leu Ile Arg Thr Leu Gly Lys Gln Leu Asn Val Asn101010151020CGT AGA GAG ATT TTA ATA AAC AAC TTC AAA TAT ATT TTT TCT CAT TTG 3120Arg Arg Glu Ile Leu Ile Asn Asn Phe Lys Tyr Ile Phe Ser His Leu1025103010351040GTC TGT TCT TGT TCC AAA GAT GAA TTA GAA CGT GCC CTT CAT TAT CTG 3168Val Cys Ser Cys Ser Lys Asp Glu Leu Glu Arg Ala Leu His Tyr Leu104510501055AAG AAT GAA ACA GAA ATT GAA CTG GGG AGC CTG TTG AGA CAA GAT TTC 3216Lys Asn Glu Thr Glu Ile Glu Leu Gly Ser Leu Leu Arg Gln Asp Phe106010651070CAA GGA TTG CAT AAT GAA TTA TTG CTG CGT ATT GGA GAA CAC TAT CAA 3264Gln Gly Leu His Asn Glu Leu Leu Leu Arg Ile Gly Glu His Tyr Gln107510801085CAG GTT TTT AAT GGT TTG TCA ATA CTT GCC TCA TTT GCA TCC AGT GAT 3312Gln Val Phe Asn Gly Leu Ser Ile Leu Ala Ser Phe Ala Ser Ser Asp109010951100GAT CCA TAT CAG GGC CCG AGA GAT ATC ATA TCA CCT GAA CTG ATG GCT 3360Asp Pro Tyr Gln Gly Pro Arg Asp Ile Ile Ser Pro Glu Leu Met Ala1105111011151120GAT TAT TTA CAA CCC AAA TTG TTG GGC ATT TTG GCT TTT TTT AAC ATG 3408Asp Tyr Leu Gln Pro Lys Leu Leu Gly Ile Leu Ala Phe Phe Asn Met112511301135CAG TTA CTG AGC TCT AGT GTT GGC ATT GAA GAT AAG AAA ATG GCC TTG 3456Gln Leu Leu Ser Ser Ser Val Gly Ile Glu Asp Lys Lys Met Ala Leu114011451150AAC AGT TTG ATG TCT TTG ATG AAG TTA ATG GGA CCC AAA CAT GTC AGT 3504Asn Ser Leu Met Ser Leu Met Lys Leu Met Gly Pro Lys His Val Ser115511601165TCT GTG AGG GTG AAG ATG ATG ACC ACA CTG AGA ACT GGC CTT CGA TTC 3552Ser Val Arg Val Lys Met Met Thr Thr Leu Arg Thr Gly Leu Arg Phe117011751180AAG GAT GAT TTT CCT GAA TTG TGT TGC AGA GCT TGG GAC TGC TTT GTT 3600Lys Asp Asp Phe Pro Glu Leu Cys Cys Arg Ala Trp Asp Cys Phe Val1185119011951200CGC TGC CTG GAT CAT GCT TGT CTG GGC TCC CTT CTC AGT CAT GTA ATA 3648Arg Cys Leu Asp His Ala Cys Leu Gly Ser Leu Leu Ser His Val Ile120512101215GTA GCT TTG TTA CCT CTT ATA CAC ATC CAG CCT AAA GAA ACT GCA GCT 3696Val Ala Leu Leu Pro Leu Ile His Ile Gln Pro Lys Glu Thr Ala Ala122012251230ATC TTC CAC TAC CTC ATA ATT GAA AAC AGG GAT GCT GTG CAA GAT TTT 3744Ile Phe His Tyr Leu Ile Ile Glu Asn Arg Asp Ala Val Gln Asp Phe123512401245CTT CAT GAA ATA TAT TTT TTA CCT GAT CAT CCA GAA TTA AAA AAG ATA 3792Leu His Glu Ile Tyr Phe Leu Pro Asp His Pro Glu Leu Lys Lys Ile125012551260AAA GCC GTT CTC CAG GAA TAC AGA AAG GAG ACC TCT GAG AGC ACT GAT 3840Lys Ala Val Leu Gln Glu Tyr Arg Lys Glu Thr Ser Glu Ser Thr Asp1265127012751280CTT CAG ACA ACT CTT CAG CTC TCT ATG AAG GCC ATT CAA CAT GAA AAT 3888Leu Gln Thr Thr Leu Gln Leu Ser Met Lys Ala Ile Gln His Glu Asn128512901295GTC GAT GTT CGT ATT CAT GCT CTT ACA AGC TTG AAG GAA ACC TTG TAT 3936Val Asp Val Arg Ile His Ala Leu Thr Ser Leu Lys Glu Thr Leu Tyr130013051310AAA AAT CAG GAA AAA CTG ATA AAG TAT GCA ACA GAC AGT GAA ACA GTA 3984Lys Asn Gln Glu Lys Leu Ile Lys Tyr Ala Thr Asp Ser Glu Thr Val131513201325GAA CCT ATT ATC TCA CAG TTG GTG ACA GTG CTT TTG AAA GGT TGC CAA 4032Glu Pro Ile Ile Ser Gln Leu Val Thr Val Leu Leu Lys Gly Cys Gln133013351340GAT GCA AAC TCT CAA GCT CGG TTG CTC TGT GGG GAA TGT TTA GGG GAA 4080Asp Ala Asn Ser Gln Ala Arg Leu Leu Cys Gly Glu Cys Leu Gly Glu1345135013551360TTG GGG GCG ATA GAT CCA GGT CGA TTA GAT TTC TCA ACA ACT GAA ACT 4128Leu Gly Ala Ile Asp Pro Gly Arg Leu Asp Phe Ser Thr Thr Glu Thr136513701375CAA GGA AAA GAT TTT ACA TTT GTG ACT GGA GTA GAA GAT TCA AGC TTT 4176Gln Gly Lys Asp Phe Thr Phe Val Thr Gly Val Glu Asp Ser Ser Phe138013851390GCC TAT GGA TTA TTG ATG GAG CTA ACA AGA GCT TAC CTT GCG TAT GCT 4224Ala Tyr Gly Leu Leu Met Glu Leu Thr Arg Ala Tyr Leu Ala Tyr Ala139514001405GAT AAT AGC CGA GCT CAA GAT TCA GCT GCC TAT GCC ATT CAG GAG TTG 4272Asp Asn Ser Arg Ala Gln Asp Ser Ala Ala Tyr Ala Ile Gln Glu Leu141014151420CTT TCT ATT TAT GAC TGT AGA GAG ATG GAG ACC AAC GGC CCA GGT CAC 4320Leu Ser Ile Tyr Asp Cys Arg Glu Met Glu Thr Asn Gly Pro Gly His1425143014351440CAA TTG TGG AGG AGA TTT CCT GAG CAT GTT CGG GAA ATA CTA GAA CCT 4368Gln Leu Trp Arg Arg Phe Pro Glu His Val Arg Glu Ile Leu Glu Pro144514501455CAT CTA AAT ACC AGA TAC AAG AGT TCT CAG AAG TCA ACC GAT TGG TCT 4416His Leu Asn Thr Arg Tyr Lys Ser Ser Gln Lys Ser Thr Asp Trp Ser146014651470GGA GTA AAG AAG CCA ATT TAC TTA AGT AAA TTG GGT AGT AAC TTT GCA 4464Gly Val Lys Lys Pro Ile Tyr Leu Ser Lys Leu Gly Ser Asn Phe Ala147514801485GAA TGG TCA GCA TCT TGG GCA GGT TAT CTT ATT ACA AAG GTT CGA CAT 4512Glu Trp Ser Ala Ser Trp Ala Gly Tyr Leu Ile Thr Lys Val Arg His149014951500GAT CTT GCC AGT AAA ATT TTC ACC TGC TGT AGC ATT ATG ATG AAG CAT 4560Asp Leu Ala Ser Lys Ile Phe Thr Cys Cys Ser Ile Met Met Lys His1505151015151520GAT TTC AAA GTG ACC ATC TAT CTT CTT CCA CAT ATT CTG GTG TAT GTC 4608Asp Phe Lys Val Thr Ile Tyr Leu Leu Pro His Ile Leu Val Tyr Val152515301535TTA CTG GGT TGT AAT CAA GAA GAT CAG CAG GAG GTT TAT GCA GAA ATT 4656Leu Leu Gly Cys Asn Gln Glu Asp Gln Gln Glu Val Tyr Ala Glu Ile154015451550ATG GCA GTT CTA AAG CAT GAC GAT CAG CAT ACC ATA AAT ACC CAA GAC 4704Met Ala Val Leu Lys His Asp Asp Gln His Thr Ile Asn Thr Gln Asp155515601565ATT GCA TCT GAT CTG TGT CAA CTC AGT ACA CAG ACT GTG TTC TCC ATG 4752Ile Ala Ser Asp Leu Cys Gln Leu Ser Thr Gln Thr Val Phe Ser Met157015751580CTT GAC CAT CTC ACA CAG TGG GCA AGG CAC AAA TTT CAG GCA CTG AAA 4800Leu Asp His Leu Thr Gln Trp Ala Arg His Lys Phe Gln Ala Leu Lys1585159015951600GCT GAG AAA TGT CCA CAC AGC AAA TCA AAC AGA AAT AAG GTA GAC TCA 4848Ala Glu Lys Cys Pro His Ser Lys Ser Asn Arg Asn Lys Val Asp Ser160516101615ATG GTA TCT ACT GTG GAT TAT GAA GAC TAT CAG AGT GTA ACC CGT TTT 4896Met Val Ser Thr Val Asp Tyr Glu Asp Tyr Gln Ser Val Thr Arg Phe162016251630CTA GAC CTC ATA CCC CAG GAT ACT CTG GCA GTA GCT TCC TTT CGC TCC 4944Leu Asp Leu Ile Pro Gln Asp Thr Leu Ala Val Ala Ser Phe Arg Ser163516401645AAA GCA TAC ACA CGA GCT GTA ATG CAC TTT GAA TCA TTT ATT ACA GAA 4992Lys Ala Tyr Thr Arg Ala Val Met His Phe Glu Ser Phe Ile Thr Glu165016551660AAG AAG CAA AAT ATT CAG GAA CAT CTT GGA TTT TTA CAG AAA TTG TAT 5040Lys Lys Gln Asn Ile Gln Glu His Leu Gly Phe Leu Gln Lys Leu Tyr1665167016751680GCT GCT ATG CAT GAA CCT GAT GGA GTG GCC GGA GTC AGT GCA ATT AGA 5088Ala Ala Met His Glu Pro Asp Gly Val Ala Gly Val Ser Ala Ile Arg168516901695AAG GCA GAA CCA TCT CTA AAA GAA CAG ATC CTT GAA CAT GAA AGC CTT 5136Lys Ala Glu Pro Ser Leu Lys Glu Gln Ile Leu Glu His Glu Ser Leu170017051710GGC TTG CTG AGG GAT GCC ACT GCT TGT TAT GAC AGG GCT ATT CAG CTA 5184Gly Leu Leu Arg Asp Ala Thr Ala Cys Tyr Asp Arg Ala Ile Gln Leu171517201725GAA CCA GAC CAG ATC ATT CAT TAT CAT GGT GTA GTA AAG TCC ATG TTA 5232Glu Pro Asp Gln Ile Ile His Tyr His Gly Val Val Lys Ser Met Leu173017351740GGT CTT GGT CAG CTG TCT ACT GTT ATC ACT CAG GTG AAT GGA GTG CAT 5280Gly Leu Gly Gln Leu Ser Thr Val Ile Thr Gln Val Asn Gly Val His1745175017551760GCT AAC AGG TCC GAG TGG ACA GAT GAA TTA AAC ACG TAC AGA GTG GAA 5328Ala Asn Arg Ser Glu Trp Thr Asp Glu Leu Asn Thr Tyr Arg Val Glu176517701775GCA GCT TGG AAA TTG TCA CAG TGG GAT TTG GTG GAA AAC TAT TTG GCA 5376Ala Ala Trp Lys Leu Ser Gln Trp Asp Leu Val Glu Asn Tyr Leu Ala178017851790GCA GAT GGA AAA TCT ACA ACA TGG AGT GTC AGA CTG GGA CAG CTA TTA 5424Ala Asp Gly Lys Ser Thr Thr Trp Ser Val Arg Leu Gly Gln Leu Leu179518001805TTA TCA GCC AAA AAA AGA GAT ATC ACA GCT TTT TAT GAC TCA CTG AAA 5472Leu Ser Ala Lys Lys Arg Asp Ile Thr Ala Phe Tyr Asp Ser Leu Lys181018151820CTA GTG AGA GCA GAA CAA ATT GTA CCT CTT TCA GCT GCA AGC TTT GAA 5520Leu Val Arg Ala Glu Gln Ile VAl Pro Leu Ser Ala Ala Ser Phe Glu1825183018351840AGA GGC TCC TAC CAA CGA GGA TAT GAA TAT ATT GTG AGA TTG CAC ATG 5568Arg Gly Ser Tyr Gln Arg Gly Tyr Glu Tyr Ile Val Arg Leu His Met184518501855TTA TGT GAG TTG GAG CAT AGC ATC AAA CCA CTT TTC CAG CAT TCT CCA 5616Leu Cys Glu Leu Glu His Ser Ile Lys Pro Leu Phe Gln His Ser Pro186018651870GGT GAC AGT TCT CAA GAA GAT TCT CTA AAC TGG GTA GCT CGA CTA GAA 5664Gly Asp Ser Ser Gln Glu Asp Ser Leu Asn Trp Val Ala Arg Leu Glu187518801885ATG ACC CAG AAT TCC TAC AGA GCC AAG GAG CCT ATC CTG GCT CTC CGG 5712Met Thr Gln Asn Ser Tyr Arg Ala Lys Glu Pro Ile Leu Ala Leu Arg189018951900AGG GCT TTA CTA AGC CTC AAC AAA AGA CCA GAT TAC AAT GAA ATG GTT 5760Arg Ala Leu Leu Ser Leu Asn Lys Arg Pro Asp Tyr Asn Glu Met Val1905191019151920GGA GAA TGC TGG CTG CAG AGT GCC AGG GTA GCT AGA AAG GCT GGT CAC 5808Gly Glu Cys Trp Leu Gln Ser Ala Arg Val Ala Arg Lys Ala Gly His192519301935CAC CAG ACA GCC TAC AAT GCT CTC CTT AAT GCA GGG GAA TCA CGA CTC 5856His Gln Thr Ala Tyr Asn Ala Leu Leu Asn Ala Gly Glu Ser Arg Leu194019451950GCT GAA CTG TAC GTG GAA AGG GCA AAG TGG CTC TGG TCC AAG GGT GAT 5904Ala Glu Leu Tyr Val Glu Arg Ala Lys Trp Leu Trp Ser Lys Gly Asp195519601965GTT CAC CAG GCA CTA ATT GTT CTT CAA AAA GGT GTT GAA TTA TGT TTT 5952Val His Gln Ala Leu Ile Val Leu Gln Lys Gly Val Glu Leu Cys Phe197019751980CCT GAA AAT GAA ACC CCA CCT GAG GGT AAG AAC ATG TTA ATC CAT GGT 6000Pro Glu Asn Glu Thr Pro Pro Glu Gly Lys Asn Met Leu Ile His Gly1985199019952000CGA GCT ATG CTA CTA GTG GGC CGA TTT ATG GAA GAA ACA GCT AAC TTT 6048Arg Ala Met Leu Leu Val Gly Arg Phe Met Glu Glu Thr Ala Asn Phe200520102015GAA AGC AAT GCA ATT ATG AAA AAA TAT AAG GAT GTG ACC GCG TGC CTG 6096Glu Ser Asn Ala Ile Met Lys Lys Tyr Lys Asp Val Thr Ala Cys Leu202020252030CCA GAA TGG GAG GAT GGG CAT TTT TAC CTT GCC AAG TAC TAT GAC AAA 6144Pro Glu Trp Glu Asp Gly His Phe Tyr Leu Ala Lys Tyr Tyr Asp Lys203520402045TTG ATG CCC ATG GTC ACA GAC AAC AAA ATG GAA AAG CAA GGT GAT CTC 6192Leu Met Pro Met Val Thr Asp Asn Lys Met Glu Lys Gln Gly Asp Leu205020552060ATC CGG TAT ATA GTT CTT CAT TTT GGC AGA TCT CTA CAA TAT GGA AAT 6240Ile Arg Tyr Ile Val Leu His Phe Gly Arg Ser Leu Gln Tyr Gly Asn2065207020752080CAG TTC ATA TAT CAG TCA ATG CCA CGA ATG TTA ACT CTA TGG CTT GAT 6288Gln Phe Ile Tyr Gln Ser Met Pro Arg Met Leu Thr Leu Trp Leu Asp208520902095TAT GGT ACA AAG GCA TAT GAA TGG GAA AAA GCT GGC CGC TCC GAT CGT 6336Tyr Gly Thr Lys Ala Tyr Glu Trp Glu Lys Ala Gly Arg Ser Asp Arg210021052110GTA CAA ATG AGG AAT GAT TTG GGT AAA ATA AAC AAG GTT ATC ACA GAG 6384Val Gln Met Arg Asn Asp Leu Gly Lys Ile Asn Lys Val Ile Thr Glu211521202125CAT ACA AAC TAT TTA GCT CCA TAT CAA TTT TTG ACT GCT TTT TCA CAA 6432His Thr Asn Tyr Leu Ala Pro Tyr Gln Phe Leu Thr Ala Phe Ser Gln213021352140TTG ATC TCT CGA ATT TGT CAT TCT CAC GAT GAA GTT TTT GTT GTC TTG 6480Leu Ile Ser Arg Ile Cys His Ser His Asp Glu Val Phe Val Val Leu2145215021552160ATG GAA ATA ATA GCC AAA GTA TTT CTA GCC TAT CCT CAA CAA GCA ATG 6528Met Glu Ile Ile Ala Lys Val Phe Leu Ala Tyr Pro Gln Gln Ala Met216521702175TGG ATG ATG ACA GCT GTG TCA AAG TCA TCT TAT CCC ATG CGT GTG AAC 6576Trp Met Met Thr Ala Val Ser Lys Ser Ser Tyr Pro Met Arg Val Asn218021852190AGA TGC AAG GAA ATC CTC AAT AAA GCT ATT CAT ATG AAA AAA TCC TTA 6624Arg Cys Lys Glu Ile Leu Asn Lys Ala Ile His Met Lys Lys Ser Leu219522002205GAG AAG TTT GTT GGA GAT GCA ACT CGC CTA ACA GAT AAG CTT CTA GAA 6672Glu Lys Phe Val Gly Asp Ala Thr Arg Leu Thr Asp Lys Leu Leu Glu221022152220TTG TGC AAT AAA CCG GTT GAT GGA AGT AGT TCC ACA TTA AGC ATG AGC 6720Leu Cys Asn Lys Pro Val Asp Gly Ser Ser Ser Thr Leu Ser Met Ser2225223022352240ACT CAT TTT AAA ATG CTT AAA AAG CTG GTA GAA GAA GCA ACA TTT AGT 6765Thr His Phe Lys Met Leu Lys Lys Leu Val Glu Glu Ala Thr Phe Ser224522502255GAA ATC CTC ATT CCT CTA CAA TCA GTC ATG ATA CCT ACA CTT CCA TCA 6816Glu Ile Leu Ile Pro Leu Gln Ser Val Met Ile Pro Thr Leu Pro Ser226022652270ATT CTG GGT ACC CAT GCT AAC CAT GCT AGC CAT GAA CCA TTT CCT GGA 6864Ile Leu Gly Thr His Ala Asn His Ala Ser His Glu Pro Phe Pro Gly227522802285CAT TGG GCC TAT ATT GCA GGG TTT GAT GAT ATG GTG GAA ATT CTT GCT 6911His Trp Ala Tyr Ile Ala Gly Phe Asp Asp Met Val Glu Ile Leu Ala229022952300TCT CTT CAG AAA CCA AAG AAG ATT TCT TTA AAA GGC TCA GAT GGA AAG 6961Ser Leu Gln Lys Pro Lys Lys Ile Ser Leu Lys Gly Ser Asp Gly Lys2305231023152320TTC TAC ATC ATG ATG TGT AAG CCA AAA GAT GAC CTG AGA AAG GAT TGT 7006Phe Tyr Ile Met Met Cys Lys Pro Lys Asp Asp Leu Arg Lys Asp Cys232523302335AGA CTA ATG GAA TTC AAT TCC TTG ATT AAT AAG TGC TTA AGA AAA GAT 7056Arg Leu Met Glu Phe Asn Ser Leu Ile Asn Lys Cys Leu Arg Lys Asp234023452350GCA GAG TCT CGT AGA AGA GAA CTT CAT ATT CGA ACA TAT GCA GTT ATT 7104Ala Glu Ser Arg Arg Arg Glu Leu His Ile Arg Thr Tyr Ala Val Ile235523602365CCA CTA AAT GAT GAA TGT GGG ATT ATT GAA TGG GTG AAC AAC ACT GCT 7151Pro Leu Asn Asp Glu Cys Gly Ile Ile Glu Trp Val Asn Asn Thr Ala237023752380GGT TTG AGA CCT ATT CTG ACC AAA CTA TAT AAA GAA AAG GGA GTG TAT 7201Gly Leu Arg Pro Ile Leu Thr Lys Leu Tyr Lys Glu Lys Gly Val Tyr2385239023952400ATG ACA GGA AAA GAA CTT CGC CAG TGT ATG CTA CCA AAG TCA GCA GCT 7246Met Thr Gly Lys Glu Leu Arg Gln Cys Met Leu Pro Lys Ser Ala Ala240524102415TTA TCT GAA AAA CTC AAA GTA TTC CGA GAA TTT CTC CTG CCC AGG CAT 7296Leu Ser Glu Lys Leu Lys Val Phe Arg Glu Phe Leu Leu Pro Arg His242024252430CCT CCT ATT TTT CAT GAG TGG TTT CTG AGA ACA TTC CCT GAT CCT ACA 7344Pro Pro Ile Phe His Glu Trp Phe Leu Arg Thr Phe Pro Asp Pro Thr243524402445TCA TGG TAC AGT AGT AGA TCA GCT TAC TGC CGT TCC ACT GCA GTA ATG 7392Ser Trp Tyr Ser Ser Arg Ser Ala Tyr Cys Arg Ser Thr Ala Val Met245024552460TCA ATG GTT GGT TAT ATT CTG GGG CTT GGA GAC CGT CAT GGT GAA AAT 7440Ser Met Val Gly Tyr Ile Leu Gly Leu Gly Asp Arg His Gly Glu Ast2465247024752450ATT CTC TTT GAT TCT TTG ACT GGT GAA TGC GTA CAT GTA GAT TTC AAT 7488Ile Leu Phe Asp Ser Leu Thr Gly Glu Cys Val His Val Asp Phe Asn248524902495TGT CTT TTC AAT AAG GGA GAA ACC TTT GAA GTT CCA GAA ATT GTG CCA 7536Cys Leu Phe Asn Lys Gly Glu Thr Phe Glu Val Pro Glu Ile Val Pro250025052510TTT CGC CTG ACT CAT AAT ATG GTT AAT GGA ATG GGT CCT ATG GGA ACA 7584Phe Arg Leu Thr His Asn Met Val Asn Gly Met Gly Pro Met Gly Thr251525202525GAG GGT CTT TTT CGA AGA GCA TGT GAA GTT ACA ATG AGG CTG ATG CGT 7632Glu Gly Leu Phe Arg Arg Ala Cys Glu Val Thr Met Arg Leu Met Arg253025352540GAT CAG CGA GAG CCT TTA ATG AGT GTC TTA AAG ACT TTT CTA CAT GAT 7680Asp Gln Arg Glu Pro Leu Met Ser Val Leu Lys Thr Phe Leu His Asp2545255025552560CCT CTT GTG GAA TGG AGT AAA CCA GTG AAA GGG CAT TCC AAA GCG CCA 7725Pro Leu Val Glu Trp Ser Lys Pro Val Lys Gly His Ser Lys Ala Pro256525702575CTG AAT GAA ACT GGA GAA GTT GTC AAT GAA AAG GCC AAG ACC CAT GTT 7776Leu Asn Glu Thr Gly Glu Val Val Asn Glu Lys Ala Lys Thr His Val258025852590CTT GAC ATT GAG CAG CGA CTA CAA GGT GTA ATC AAG ACT CGA AAT AGA 7824Leu Asp Ile Glu Gln Arg Leu Gln Gly Val Ile Lys Thr Arg Asn Arg259526002605GTG ACA GGA CTG CCG TTA TCT ATT GAA GGA CAT GTG CAT TAC CTT ATA 7872Val Thr Gly Leu Pro Leu Ser Ile Glu Gly His Val His Tyr Leu Ile261026152620CAA GAA GCT ACT GAT GAA AAC TTA CTA TGC CAG ATG TAT CTT GGT TGG 7920Gln Glu Ala Thr Asp Glu Asn Leu Leu Cys Gln Met Tyr Leu Gly Trp2625263026352640ACT CCA TAT ATG TGA 7935Thr Pro Tyr Met(2)SEQ ID NO29的说明(i)序列特征(A)长度2644个氨基酸(B)类型氨基酸(D)拓扑结构线性(ii)分子类型蛋白(xi)序列描述SEQ ID NO29Met Gly Glu His Gly Leu Glu Leu Ala Ser Met Ile Pro Ala Leu Arg1 5 10 15Glu Leu Gly Ser Ala Thr Pro Glu Glu Tyr Asn Thr Val Val Gln Lys20 25 30Pro Arg Gln Ile Leu Cys Gln Phe Ile Asp Arg Ile Leu Thr Asp Val35 40 45Asn Val Val Ala Val Glu Leu Val Lys Lys Thr Asp Ser Gln Pro Thr50 55 60Ser Val Met Leu Leu Asp Phe Ile Gln His Ile Met Lys Ser Ser Pro65 70 75 80Leu Met Phe Val Asn Val Ser Gly Ser His Glu Arg Lys Gly Ser Cys85 90 95Ile Glu Phe Ser Asn Trp Ile Ile Thr Arg Leu Leu Arg Ile Ala Ala100 105 110Thr Pro Ser Cys His Leu Leu His Lys Lys Ile Cys Glu Val Ile Cys115 120 125Ser Leu Leu Phe Leu Phe Lys Ser Lys Ser Pro Ala Ile Phe Gly Val130 135 140Leu Thr Lys Glu Leu Leu Gln Leu Phe Glu Asp Leu Val Tyr Leu His145 150 155 160Arg Arg Asn Val Met Gly His Ala Val Glu Trp Pro Val Val Met Ser165 170 175Arg Phe Leu Ser Gln Leu Asp Glu His Met Gly Tyr Leu Gln Ser Ala180 185 190Pro Leu Gln Leu Met Ser Met Gln Asn Leu Glu Phe Ile Glu Val Thr195 200 205Leu Leu Met Val Leu Thr Arg Ile Ile Ala Ile Val Phe Phe Arg Arg210 215 220Gln Glu Leu Leu Leu Trp Gln Ile Gly Cys Val Leu Leu Glu Tyr Gly225 230 235 240Ser Pro Lys Ile Lys Ser Leu Ala Ile Ser Phe Leu Thr Glu Leu Phe245 250 255Gln Leu Gly Gly Leu Pro Ala Gln Pro Ala Ser Thr Phe Phe Ser Ser260 265 270Phe Leu Glu Leu Leu Lys His Leu Val Glu Met Asp Thr Asp Gln Leu275 280 285Lys Leu Tyr Glu Glu Pro Leu Ser Lys Leu Ile Lys Thr Leu Phe Pro290 295 300Phe Glu Ala Glu Ala Tyr Arg Asn Ile Glu Pro Val Tyr Leu Asn Met305 310 315 320Leu Leu Glu Lys Leu Cys Val Met Phe Glu Asp Gly Val Leu Met Arg325 330 335Leu Lys Ser Asp Leu Leu Lys Ala Ala Leu Cys His Leu Leu Gln Tyr340 345 350Phe Leu Lys Phe Val Pro Ala Gly Tyr Glu Ser Ala Leu Gln Val Arg355 360 365Lys Val Tyr Val Arg Asn Ile Cys Lys Ala Leu Leu Asp Val Leu Gly370 375 380Ile Glu Val Asp Ala Glu Tyr Leu Leu Gly Pro Leu Tyr Ala Ala Leu385 390 395 400Lys Met Glu Ser Met Glu Ile Ile Glu Glu Ile Gln Cys Gln Thr Gln405 410 415Gln Glu Asn Leu Ser Ser Asn Ser Asp Gly Ile Ser Pro Lys Arg Arg420 425 430Arg Leu Ser Ser Ser Leu Asn Pro Ser Lys Arg Ala Pro Lys Gln Thr435 440 445Glu Glu Ile Lys His Val Asp Met Asn Gln Lys Ser Ile Leu Trp Ser450 455 460Ala Leu Lys Gln Lys Ala Glu Ser Leu Gln Ile Ser Leu Glu Tyr Ser465 470 475 480Gly Leu Lys Asn Pro Val Ile Glu Met Leu Glu Gly Ile Ala Val Val485 490 495Leu Gln Leu Thr Ala Leu Cys Thr Val His Cys Ser His Gln Asn Met500 505 510Asn Cys Arg Thr Phe Lys Asp Cys Gln His Lys Ser Lys Lys Lys Pro515 520 525Ser Val Val Ile Thr Trp Met Ser Leu Asp Phe Tyr Thr Lys Val Leu530 535 540Lys Ser Cys Arg Ser Leu Leu Glu Ser Val Gln Lys Leu Asp Leu Glu545 550 555 560Ala Thr Ile Asp Lys Val Val Lys Ile Tyr Asp Ala Leu Ile Tyr Met565 570 575Gln Val Asn Ser Ser Phe Glu Asp His Ile Leu Glu Asp Leu Cys Gly580 585 590Met Leu Ser Leu Pro Trp Ile Tyr Ser His Ser Asp Asp Gly Cys Leu595 600 605Lys Leu Thr Thr Phe Ala Ala Asn Leu Leu Thr Leu Ser Cys Arg Ile610 615 620Ser Asp Ser Tyr Ser Pro Gln Ala Gln Ser Arg Cys Val Phe Leu Leu625 630 635 640Thr Leu Phe Pro Arg Arg Ile Phe Leu Glu Trp Arg Thr Ala Val Tyr645 650 655Asn Trp Ala Leu Gln Ser Ser His Glu Val Ile Arg Ala Ser Cys Val660 665 670Ser Gly Phe Phe Ile Leu Leu Gln Gln Gln Asn Ser Cys Asn Arg Val675 680 685Pro Lys Ile Leu Ile Asp Lys Val Lys Asp Asp Ser Asp Ile Val Lys690 695 700Lys Glu Phe Ala Ser Ile Leu Gly Gln Leu Val Cys Thr Leu His Gly705 710 715 720Met Phe Tyr Leu Thr Ser Ser Leu Thr Glu Pro Phe Ser Glu His Gly725 730 735His Val Asp Leu Phe Cys Arg Asn Leu Lys Ala Thr Ser Gln His Glu740 745 750Cys Ser Ser Ser Gln Leu Lys Ala Ser Val Cys Lys Pro Phe Leu Phe755 760 765Leu Leu Lys Lys Lys Ile Pro Ser Pro Val Lys Leu Ala Phe Ile Asp770 775 780Asn Leu His His Leu Cys Lys His Leu Asp Phe Arg Glu Asp Glu Thr785 790 795 800Asp Val Lys Ala Val Leu Gly Thr Leu Leu Asn Leu Met Glu Asp Pro805 810 815Asp Lys Asp Val Arg Val Ala Phe Ser Gly Asn Ile Lys His Ile Leu820 825 830Glu Ser Leu Asp Ser Glu Asp Gly Phe Ile Lys Glu Leu Phe Val Leu835 840 845Arg Met Lys Glu Ala Tyr Thr His Ala Gln Ile Ser Arg Asn Asn Glu850 855 860Leu Lys Asp Thr Leu Ile Leu Thr Thr Gly Asp Ile Gly Arg Ala Ala865 870 875 880Lys Gly Asp Leu Val Pro Phe Ala Leu Leu His Leu Leu His Cys Leu885 890 895Leu Ser Lys Ser Ala Ser Val Ser Gly Ala Ala Tyr Thr Glu Ile Arg900 905 910Ala Leu Val Ala Ala Lys Ser Val Lys Leu Gln Ser Phe Phe Ser Gln915 920 925Tyr Lys Lys Pro Ile Cys Gln Phe Leu Val Glu Ser Leu His Ser Ser930 935 940Gln Met Thr Ala Leu Pro Asn Thr Pro Cys Gln Asn Ala Asp Val Arg945 950 955 960Lys Gln Asp Val Ala His Gln Arg Glu Met Ala Leu Asn Thr Leu Ser965 970 975Glu Ile Ala Asn Val Phe Asp Phe Pro Asp Leu Asn Arg Phe Leu Thr980 985 990Arg Thr Leu Gln Val Leu Leu Pro Asp Leu Ala Ala Lys Ala Ser Pro995 10001005Ala Ala Ser Ala Leu Ile Arg Thr Leu Gly Lys Gln Leu Asn Val Asn101010151020Arg Arg Glu Ile Leu Ile Asn Asn Phe Lys Tyr Ile Phe Ser His Leu1025103010351040Val Cys Ser Cys Ser Lys Asp Glu Leu Glu Arg Ala Leu His Tyr Leu104510501055Lys Asn Glu Thr Glu Ile Glu Leu Gly Ser Leu Leu Arg Gln Asp Phe106010651070Gln Gly Leu His Asn Glu Leu Leu Leu Arg Ile Gly Glu His Tyr Gln107510801085Gln Val Phe Asn Gly Leu Ser Ile Leu Ala Ser Phe Ala Ser Ser Asp109010951100Asp Pro Tyr Gln Gly Pro Arg Asp Ile Ile Ser Pro Glu Leu Met Ala1105111011151120Asp Tyr Leu Gln Pro Lys Leu Leu Gly Ile Leu Ala Phe Phe Asn Met112511301135Gln Leu Leu Ser Ser Ser Val Gly Ile Glu Asp Lys Lys Met Ala Leu114011451150Asn Ser Leu Met Ser Leu Met Lys Leu Met Gly Pro Lys His Val Ser115511601165Ser Val Arg Val Lys Met Met Thr Thr Leu Arg Thr Gly Leu Arg Phe117011751180Lys Asp Asp Phe Pro Glu Leu Cys Cys Arg Ala Trp Asp Cys Phe Val1185119011951200Arg Cys Leu Asp His Ala Cys Leu Gly Ser Leu Leu Ser His Val Ile120512101215Val Ala Leu Leu Pro Leu Ile His Ile Gln Pro Lys Glu Thr Ala Ala122012251230Ile Phe His Tyr Leu Ile Ile Glu Asn Arg Asp Ala Val Gln Asp Phe123512401245Leu His Glu Ile Tyr Phe Leu Pro Asp His Pro Glu Leu Lys Lys Ile125012551260Lys Ala Val Leu Gln Glu Tyr Arg Lys Glu Thr Ser Glu Ser Thr Asp1265127012751280Leu Gln Thr Thr Leu Gln Leu Ser Met Lys Ala Ile Gln His Glu Asn128512901295Val Asp Val Arg Ile His Ala Leu Thr Ser Leu Lys Glu Thr Leu Tyr130013051310Lys Asn Gln Glu Lys Leu Ile Lys Tyr Ala Thr Asp Ser Glu Thr Val131513201325Glu Pro Ile Ile Ser Gln Leu Val Thr Val Leu Leu Lys Gly Cys Gln133013351340Asp Ala Asn Ser Gln Ala Arg Leu Leu Cys Gly Glu Cys Leu Gly Glu1345135013551360Leu Gly Ala Ile Asp Pro Gly Arg Leu Asp Phe Ser Thr Thr Glu Thr136513701375Gln Gly Lys Asp Phe Thr Phe Val Thr Gly Val Glu Asp Ser Ser Phe138013851390Ala Tyr Gly Leu Leu Met Glu Leu Thr Arg Ala Tyr Leu Ala Tyr Ala139514001405Asp Asn Ser Arg Ala Gln Asp Ser Ala Ala Tyr Ala Ile Gln Glu Leu141014151420Leu Ser Ile Tyr Asp Cys Arg Glu Met Glu Thr Asn Gly Pro Gly His1425143014351440Gln Leu Trp Arg Arg Phe Pro Glu His Val Arg Glu Ile Leu Glu Pro144514501455His Leu Asn Thr Arg Tyr Lys Ser Ser Gln Lys Ser Thr Asp Trp Ser146014651470Gly Val Lys Lys Pro Ile Tyr Leu Ser Lys Leu Gly Ser Asn Phe Ala147514801485Glu Trp Ser Ala Ser Trp Ala Gly Tyr Leu Ile Thr Lys Val Arg His149014951500Asp Leu Ala Ser Lys Ile Phe Thr Cys Cys Ser Ile Met Met Lys His1505151015151520Asp Phe Lys Val Thr Ile Tyr Leu Leu Pro His Ile Leu Val Tyr Val152515301535Leu Leu Gly Cys Asn Gln Glu Asp Gln Gln Glu Val Tyr Ala Glu Ile154015451550Met Ala Val Leu Lys His Asp Asp Gln His Thr Ile Asn Thr Gln Asp155515601565Ile Ala Ser Asp Leu Cys Gln Leu Ser Thr Gln Thr Val Phe Ser Met157015751580Leu Asp His Leu Thr Gln Trp Ala Arg His Lys Phe Gln Ala Leu Lys1585159015951600Ala Glu Lys Cys Pro His Ser Lys Ser Asn Arg Asn Lys Val Asp Ser160516101615Met Val Ser Thr Val Asp Tyr Glu Asp Tyr Gln Ser Val Thr Arg Phe162016251630Leu Asp Leu Ile Pro Gln Asp Thr Leu Ala Val Ala Ser Phe Arg Ser163516401645Lys Ala Tyr Thr Arg Ala Val Met His Phe Glu Ser Phe Ile Thr Glu165016551660Lys Lys Gln Asn Ile Gln Glu His Leu Gly Phe Leu Gln Lys Leu Tyr1665167016751680Ala Ala Met His Glu Pro Asp Gly Val Ala Gly Val Ser Ala Ile Arg168516901695Lys Ala Glu Pro Ser Leu Lys Glu Gln Ile Leu Glu His Glu Ser Leu170017051710Gly Leu Leu Arg Asp Ala Thr Ala Cys Tyr Asp Arg Ala Ile Gln Leu171517201725Glu Pro Asp Gln Ile Ile His Tyr His Gly Val Val Lys Ser Met Leu173017351740Gly Leu Gly Gln Leu Ser Thr Val Ile Thr Gln Val Asn Gly Val His1745175017551760Ala Asn Arg Ser Glu Trp Thr Asp Glu Leu Asn Thr Tyr Arg Val Glu176517701775Ala Ala Trp Lys Leu Ser Gln Trp Asp Leu Val Glu Asn Tyr Leu Ala178017851790Ala Asp Gly Lys Ser Thr Thr Trp Ser Val Arg Leu Gly Gln Leu Leu179518001805Leu Ser Ala Lys Lys Arg Asp Ile Thr Ala Phe Tyr Asp Ser Leu Lys181018151820Leu Val Arg Ala Glu Gln Ile Val Pro Leu Ser Ala Ala Ser Phe Glu1825183018351840Arg Gly Ser Tyr Gln Arg Gly Tyr Glu Tyr Ile Val Arg Leu His Met184518501855Leu Cys Glu Leu Glu His Ser Ile Lys Pro Leu Phe Gln His Ser Pro186018651870Gly Asp Ser Ser Gln Glu Asp Ser Leu Asn Trp Val Ala Arg Leu Glu187518801885Met Thr Gln Asn Ser Tyr Arg Ala Lys Glu Pro Ile Leu Ala Leu Arg189018951900Arg Ala Leu Leu Ser Leu Asn Lys Arg Pro Asp Tyr Asn Glu Met Val1905191019151920Gly Glu Cys Trp Leu Gln Ser Ala Arg Val Ala Arg Lys Ala Gly His192519301935His Gln Thr Ala Tyr Asn Ala Leu Leu Asn Ala Gly Glu Ser Arg Leu194019451950Ala Glu Leu Tyr Val Glu Arg Ala Lys Trp Leu Trp Ser Lys Gly Asp195519601965Val His Gln Ala Leu Ile Val Leu Gln Lys Gly Val Glu Leu Cys Phe197019751980Pro Glu Asn Glu Thr Pro Pro Glu Gly Lys Asn Met Leu Ile His Gly1985199019952000Arg Ala Met Leu Leu Val Gly Arg Phe Met Glu Glu Thr Ala Asn Phe200520102015Glu Ser Asn Ala Ile Met Lys Lys Tyr Lys Asp Val Thr Ala Cys Leu202020252030Pro Glu Trp Glu Asp Gly His Phe Tyr Leu Ala Lys Tys Tyr Asp Lys203520402045Leu Met Pro Met Val Thr Asp Asn Lys Met Glu Lys Gln Gly Asp Leu205020552060Ile Arg Tyr Ile Val Leu His Phe Gly Arg Ser Leu Gln Tyr Gly Asp2065207020752050Gln Phe Ile Tyr Gln Ser Met Pro Arg Met Leu Thr Leu Trp Leu Asp208520902095Tyr Gly Thr Lys Ala Tyr Glu Trp Glu Lys Ala Gly Arg Ser Asp Arg210021052110Val Gln Met Arg Asn Asp Leu Gly Lys Ile Asn Lys Val Ile Thr Glu211521202125His Thr Asn Tyr Leu Ala Pro Tyr Gln Phe Leu Thr Ala Phe Ser Gln213021352140Leu Ile Ser Arg Ile Cys His Ser His Asp Glu Val Phe Val Val Leu2145215021552160Met Glu Ile Ile Ala Lys Val Phe Leu Ala Tyr Pro Gln Gln Ala Met216521702175Trp Met Met Thr Ala Val Ser Lys Ser Ser Tyr Pro Met Arg Val Asn218021852190Arg Cys Lys Glu Ile Leu Asn Lys Ala Ile His Met Lys Lys Ser Leu219522002205Glu Lys Phe Val Gly Asp Ala Thr Arg Leu Thr Asp Lys Leu Leu Glu221022152220Leu Cys Asn Lys Pro Val Asp Gly Ser Ser Ser Thr Leu Ser Met Ser2225223022352240Thr His Phe Lys Met Leu Lys Lys Leu Val Glu Glu Ala Thr Phe Ser224522502255Glu Ile Leu Ile Pro Leu Gln Ser Val Met Ile Pro Thr Leu Pro Ser226022652270Ile Leu Gly Thr His Ala Asn His Ala Ser His Glu Pro Phe Pro Gly227522802285His Trp Ala Tyr Ile Ala Gly Phe Asp Asp Met Val Glu Ile Leu Ala229022952300Ser Leu Gln Lys Pro Lys Lys Ile Ser Leu Lys Gly Ser Asp Gly Lys2305231023152320Phe Tyr Ile Met Met Cys Lys Pro Lys Asp Asp Leu Arg Lys Asp Cys232523302335Arg Leu Met Glu Phe Asn Ser Leu Ile Asn Lys Cys Leu Arg Lys Asp234023452350Ala Glu Ser Arg Arg Arg Glu Leu His Ile Arg Thr Tyr Ala Val Ile235523602365Pro Leu Asn Asp Glu Cys Gly Ile Ile Glu Trp Val Asn Asn Thr Ala237023752380Gly Leu Arg Pro Ile Leu Thr Lys Leu Tyr Lys Glu Lys Gly Val Tyr2385239023952400Met Thr Gly Lys Glu Leu Arg Gln Cys Met Leu Pro Lys Ser Ala Ala240524102415Leu Ser Glu Lys Leu Lys Val Phe Arg Glu Phe Leu Leu Pro Arg His242024252430Pro Pro Ile Phe His Glu Trp Phe Leu Arg Thr Phe Pro Asp Pro Thr243524402445Ser Trp Tyr Ser Ser Arg Ser Ala Tyr Cys Arg Ser Thr Ala Val Met245024552460Ser Met Val Gly Tyr Ile Leu Gly Leu Gly Asp Arg His Gly Glu Asn2465247024752480Ile Leu Phe Asp Ser Leu Thr Gly Glu Cys Val His Val Asp Phe Asn248524902495Cys Leu Phe Asn Lys Gly Glu Thr Phe Glu Val Pro Glu Ile Val Pro250025052510Phe Arg Leu Thr His Asn Met Val Asn Gly Met Gly Pro Met Gly Thr251525202525Glu Gly Leu Phe Arg Arg Ala Cys Glu Val Thr Met Arg Leu Met Arg253025352540Asp Gln Arg Glu Pro Leu Met Ser Val Leu Lys Thr Phe Leu His Asp2545255025552560Pro Leu Val Glu Trp Ser Lys Pro Val Lys Gly His Ser Lys Ala Pro256525702575Leu Asn Glu Thr Gly Glu Val Val Asn Glu Lys Ala Lys Thr His Val258025852590Leu Asp Ile Glu Gln Arg Leu Gln Gly Val Ile Lys Thr Arg Asn Arg259526002605Val Thr Gly Leu Pro Leu Ser Ile Glu Gly His Val His Tyr Leu Ile261026152620Gln Glu Ala Thr Asp Glu Asn Leu Leu Cys Gln Met Tyr Leu Gly Trp2625263026352640Thr Pro Tyr Met(2)SEQ ID NO30的说明(i)序列特征(A)长度7624个碱基对(B)类型核苷酸(C)链型单链(D)拓扑结构线性(ii)分子类型cDNA(ix)特征(A)姓名/符号CDS(B)位置333..7562(xi)序列描述SEQ ID NO30CTTGTGAAGA GAATGTTTTA CACTCTTGTT AGTGAAGTTT ATTCTTTAAA AGTCAATCGT60CAAGGATTTA GCAAATGAAT TAGCACTTCG GATATACTTG TTTATTTAAT ATCTTTTTTG120TTTATTTCAA AGAATTCAGT AATTGGATCA TAACGAGACT TCTGCGGATT GCAGCAACTC180CCTCCTGTCA TTTGTTACAC AAGAAAATCT GTGAAGTCAT CTGTTGATTA TTATTTCTTT240TTAAAAGCAA GAGTCCTGCT ATTTTTGGGG TACTCACAAA AGAATTATTA CAACTTTTTG300AAGACTTGGT TTACCTCCAT AGAAGAAATG TG ATG GGT CAT GCT GTG GAA TGG 353Met Gly His Ala Val Glu Trp1 5CCA GTG GTC ATG AGC CGA TTT TTA AGT CAA TTA GAT GAA CAC ATG GGA 401Pro Val Val Met Ser Arg Phe Leu Ser Gln Leu Asp Glu His Met Gly10 15 20TAT TTA CAA TCA GCT CCT TTG CAG TTG ATG AGT ATG CAA AAT TTA GAA 449Tyr Leu Gln Ser Ala Pro Leu Gln Leu Met Ser Met Gln Asn Leu Glu25 30 35TTT ATT GAA GTC ACT TTA TTA ATG GTT CTT ACT CGT ATT ATT GCA ATT 497Phe Ile Glu Val Thr Leu Leu Met Val Leu Thr Arg Ile Ile Ala Ile40 45 50 55GTG TTT TTT AGA AGG CAA GAA CTC TTA CTT TGG CAG ATA GGT TGT GTT 545Val Phe Phe Arg Arg Gln Glu Leu Leu Leu Trp Gln Ile Gly Cys Val60 65 70CTG CTA GAG TAT GGT AGT CCA AAA ATT AAA TCC CTA GCA ATT AGC TTT 593Leu Leu Glu Tyr Gly Ser Pro Lys Ile Lys Ser Leu Ala Ile Ser Phe75 80 85TTA ACA GAA CTT TTT CAG CTT GGA GGA CTA CCA GCA CAA CCA GCT AGC 641Leu Thr Glu Leu Phe Gln Leu Gly Gly Leu Pro Ala Gln Pro Ala Ser90 95 100ACT TTT TTC AGC TCA TTT TTG GAA TTA TTA AAA CAC CTT GTA GAA ATG 689Thr Phe Phe Ser Ser Phe Leu Glu Leu Leu Lys His Leu Val Glu Met105 110 115GAT ACT GAC CAA TTG AAA CTC TAT GAA GAG CCA TTA TCA AAG CTG ATA 737Asp Thr Asp Gln Leu Lys Leu Tyr Glu Glu Pro Leu Ser Lys Leu Ile120 125 130 135AAG ACA CTA TTT CCC TTT GAA GCA GAA GCT TAT AGA AAT ATT GAA CCT 785Lys Thr Leu Phe Pro Phe Glu Ala Glu Ala Tyr Arg Asn Ile Glu Pro140 145 150GTC TAT TTA AAT ATG CTG CTG GAA AAA CTC TGT GTC ATG TTT GAA GAC 833Val Tyr Leu Asn Met Leu Leu Glu Lys Leu Cys Val Met Phe Glu Asp155 160 165GGT GTG CTC ATG CGG CTT AAG TCT GAT TTG CTA AAA GCA GCT TTG TGC 881Gly Val Leu Met Arg Leu Lys Ser Asp Leu Leu Lys Ala Ala Leu Cys170 175 180CAT TTA CTG CAG TAT TTC CTT AAA TTT GTG CCA GCT GGG TAT GAA TCT 929His Leu Leu Gln Tyr Phe Leu Lys Phe Val Pro Ala Gly Tyr Glu Ser185 190 195GCT TTA CAA GTC AGG AAG GTC TAT GTG AGA AAT ATT TGT AAA GCT CTT 977Ala Leu Gln Val Arg Lys Val Tyr Val Arg Asn Ile Cys Lys Ala Leu200 205 210 215TTG GAT GTG CTT GGA ATT GAG GTA GAT GCA GAG TAC TTG TTG GGC CCA 1025Leu Asp Val Leu Gly Ile Glu Val Asp Ala Glu Tyr Leu Leu Gly Pro220 225 230CTT TAT GCA GCT TTG AAA ATG GAA AGT ATG GAA ATC ATT GAG GAG ATT 1073Leu Tyr Ala Ala Leu Lys Met Glu Ser Met Glu Ile Ile Glu Glu Ile235 240 245CAA TGC CAA ACT CAA CAG GAA AAC CTC AGC AGT AAT AGT GAT GGA ATA 1121Gln Cys Gln Thr Gln Gln Glu Asn Leu Ser Ser Asn Ser Asp Gly Ile250 255 260TCA CCC AAA AGG CGT CGT CTC AGC TCG TCT CTA AAC CCT TCT AAA AGA 1169Ser Pro Lys Arg Arg Arg Leu Ser Ser Ser Leu Asn Pro Ser Lys Arg265 270 275GCA CCA AAA CAG ACT GAG GAA ATT AAA CAT GTG GAC ATG AAC CAA AAG 1217Ala Pro Lys Gln Thr Glu Glu Ile Lys His Val Asp Met Asn Gln Lys280 285 290 295AGC ATA TTA TGG AGT GCA CTG AAA CAG AAA GCT GAA TCC CTT CAG ATT 1265Ser Ile Leu Trp Ser Ala Leu Lys Gln Lys Ala Glu Ser Leu Gln Ile300 305 310TCC CTT GAA TAC AGT GGC CTA AAG AAT CCT GTT ATT GAG ATG TTA GAA 1313Ser Leu Glu Tyr Ser Gly Leu Lys Asn Pro Val Ile Glu Met Leu Glu315 320 325GGA ATT GCT GTT GTC TTA CAA CTG ACT GCT CTG TGT ACT GTT CAT TGT 1361Gly Ile Ala Val Val Leu Gln Leu Thr Ala Leu Cys Thr Val His Cys330 335 340TCT CAT CAA AAC ATG AAC TGC CGT ACT TTC AAG GAC TGT CAA CAT AAA 1409Ser His Gln Asn Met Asn Cys Arg Thr Phe Lys Asp Cys Gln His Lys345 350 355TCC AAG AAG AAA CCT TCT GTA GTG ATA ACT TGG ATG TCA TTG GAT TTT 1457Ser Lys Lys Lys Pro Ser Val Val Ile Thr Trp Met Ser Leu Asp Phe360 365 370 375TAC ACA AAA GTG CTT AAG AGC TGT AGA AGT TTG TTA GAA TCT GTT CAG 1505Tyr Thr Lys Val Leu Lys Ser Cys Arg Ser Leu Leu Glu Ser Val Gln380 385 390AAA CTG GAC CTG GAG GCA ACC ATT GAT AAG GTG GTG AAA ATT TAT GAT 1553Lys Leu Asp Leu Glu Ala Thr Ile Asp Lys Val Val Lys Ile Tyr Asp395 400 405GCT TTG ATT TAT ATG CAA GTA AAC AGT TCA TTT GAA GAT CAT ATC CTG 1601Ala Leu Ile Tyr Met Gln Val Asn Ser Ser Phe Glu Asp His Ile Leu410 415 420GAA GAT TTA TGT GGA ATG CTC TCA CTT CCA TGG ATT TAT TCC CAT TCT 1649Glu Asp Leu Cys Gly Met Leu Ser Leu Pro Trp Ile Tyr Ser His Ser425 430 435GAT GAT GGC TGT TTA AAG TTG ACC ACA TTT GCC GCT AAT CTT CTA ACA 1697Asp Asp Gly Cys Leu Lys Leu Thr Thr Phe Ala Ala Asn Leu Leu Thr440 445 450 455TTA AGC TGT AGG ATT TCA GAT AGC TAT TCA CCA CAG GCA CAA TCA CGA 1745Leu Ser Cys Arg Ile Ser Asp Ser Tyr Ser Pro Gln Ala Gln Ser Arg460 465 470TGT GTG TTT CTT CTG ACT CTG TTT CCA AGA AGA ATA TTC CTT GAG TGG 1793Cys Val Phe Leu Leu Thr Leu Phe Pro Arg Arg Ile Phe Leu Glu Trp475 480 485AGA ACA GCA GTT TAC AAC TGG GCC CTG CAG AGC TCC CAT GAA GTA ATC 1841Arg Thr Ala Val Tyr Asn Trp Ala Leu Gln Ser Ser His Glu Val Ile490 495 500CGG GCT AGT TGT GTT AGT GGA TTT TTT ATC TTA TTG CAG CAG CAG AAT 1889Arg Ala Ser Cys Val Ser Gly Phe Phe Ile Leu Leu Gln Gln Gln Asn505 510 515TCT TGT AAC AGA GTT CCC AAG ATT CTT ATA GAT AAA GTC AAA GAT GAT 1937Ser Cys Asn Arg Val Pro Lys Ile Leu Ile Asp Lys Val Lys Asp Asp520 525 530 535TCT GAC ATT GTC AAG AAA GAA TTT GCT TCT ATA CTT GGT CAA CTT GTC 1985Ser Asp Ile Val Lys Lys Glu Phe Ala Ser Ile Leu Gly Gln Leu Val540 545 550TGT ACT CTT CAC GGC ATG TTT TAT CTG ACA AGT TCT TTA ACA GAA CCT 2033Cys Thr Leu His Gly Met Phe Tyr Leu Thr Ser Ser Leu Thr Glu Pro555 560 565TTC TCT GAA CAC GGA CAT GTG GAC CTC TTC TGT AGG AAC TTG AAA GCC 2081Phe Ser Glu His Gly His Val Asp Leu Phe Cys Arg Asn Leu Lys Ala570 575 580ACT TCT CAA CAT GAA TGT TCA TCT TCT CAA CTA AAA GCT TCT GTC TGC 2129Thr Ser Gln His Glu Cys Ser Ser Ser Gln Leu Lys Ala Ser Val Cys585 590 595AAG CCA TTC CTT TTC CTA CTG AAA AAA AAA ATA CCT AGT CCA GTA AAA 2177Lys Pro Phe Leu Phe Leu Leu Lys Lys Lys Ile Pro Ser Pro Val Lys600 605 610 615CTT GCT TTC ATA GAT AAT CTA CAT CAT CTT TGT AAG CAT CTT GAT TTT 2225Leu Ala Phe Ile Asp Asn Leu His His Leu Cys Lys His Leu Asp Phe620 625 630AGA GAA GAT GAA ACA GAT GTA AAA GCA GTT CTT GGA ACT TTA TTA AAT 2273Arg Glu Asp Glu Thr Asp Val Lys Ala Val Leu Gly Thr Leu Leu Asn635 640 645TTA ATG GAA GAT CCA GAC AAA GAT GTT AGA GTG GCT TTT AGT GGA AAT 2321Leu Met Glu Asp Pro Asp Lys Asp Val Arg Val Ala Phe Ser Gly Asn650 655 660ATC AAG CAC ATA TTG GAA TCC TTG GAC TCT GAA GAT GGA TTT ATA AAG 2369Ile Lys His Ile Leu Glu Ser Leu Asp Ser Glu Asp Gly Phe Ile Lys665 670 675GAG CTT TTT GTC TTA AGA ATG AAG GAA GCA TAT ACA CAT GCC CAA ATA 2417Glu Leu Phe Val Leu Arg Met Lys Glu Ala Tyr Thr His Ala Gln Ile680 685 690 695TCA AGA AAT AAT GAG CTG AAG GAT ACC TTG ATT CTT ACA ACA GGG GAT 2465Ser Arg Asn Asn Glu Leu Lys Asp Thr Leu Ile Leu Thr Thr Gly Asp700 705 710ATT GGA AGG GCC GCA AAA GGA GAT TTG GTA CCA TTT GCA CTC TTA CAC 2513Ile Gly Arg Ala Ala Lys Gly Asp Leu Val Pro Phe Ala Leu Leu His715 720 725TTA TTG CAT TGT TTG TTA TCC AAG TCA GCA TCT GTC TCT GGA GCA GCA 2561Leu Leu His Cys Leu Leu Ser Lys Ser Ala Ser Val Ser Gly Ala Ala730 735 740TAC ACA GAA ATT AGA GCT CTG GTT GCA GCT AAA AGT GTT AAA CTG CAA 2609Tyr Thr Glu Ile Arg Ala Leu Val Ala Ala Lys Ser Val Lys Leu Gln745 750 755AGT TTT TTC AGC CAG TAT AAG AAA CCC ATC TGT CAG TTT TTG GTA GAA 2657Ser Phe Phe Ser Gln Tyr Lys Lys Pro Ile Cys Gln Phe Leu Val Glu760 765 770 775TCC CTT CAC TCT AGT CAG ATG ACA GCA CTT CCG AAT ACT CCA TGC CAG 2705Ser Leu His Ser Ser Gln Met Thr Ala Leu Pro Asn Thr Pro Cys Gln780 785 790AAT GCT GAC GTG CGA AAA CAA GAT GTG GCT CAC CAG AGA GAA ATG GCT 2753Asn Ala Asp Val Arg Lys Gln Asp Val Ala His Gln Arg Glu Met Ala795 800 805TTA AAT ACG TTG TCT GAA ATT GCC AAC GTT TTC GAC TTT CCT GAT CTT 2801Leu Asn Thr Leu Ser Glu Ile Ala Asn Val Phe Asp Phe Pro Asp Leu810 815 820AAT CGT TTT CTT ACT AGG ACA TTA CAA GTT CTA CTA CCT GAT CTT GCT 2849Asn Arg Phe Leu Thr Arg Thr Leu Gln Val Leu Leu Pro Asp Leu Ala825 830 835GCC AAA GCA AGC CCT GCA GCT TCT GCT CTC ATT CGA ACT TTA GGA AAA 2897Ala Lys Ala Ser Pro Ala Ala Ser Ala Leu Ile Arg Thr Leu Gly Lys840 845 850 855CAA TTA AAT GTC AAT CGT AGA GAG ATT TTA ATA AAC AAC TTC AAA TAT 2945Gln Leu Asn Val Asn Arg Arg Glu Ile Leu Ile Asn Asn Phe Lys Tyr860 865 870ATT TTT TCT CAT TTG GTC TGT TCT TGT TCC AAA GAT GAA TTA GAA CGT 2993Ile Phe Ser His Leu Val Cys Ser Cys Ser Lys Asp Glu Leu Glu Arg875 880 885GCC CTT CAT TAT CTG AAG AAT GAA ACA GAA ATT GAA CTG GGG AGC CTG 3041Ala Leu His Tyr Leu Lys Asn Glu Thr Glu Ile Glu Leu Gly Ser Leu890 895 900TTG AGA CAA GAT TTC CAA GGA TTG CAT AAT GAA TTA TTG CTG CGT ATT 3089Leu Arg Gln Asp Phe Gln Gly Leu His Asn Glu Leu Leu Leu Arg Ile905 910 915GGA GAA CAC TAT CAA CAG GTT TTT AAT GGT TTG TCA ATA CTT GCC TCA 3137Gly Glu His Tyr Gln Gln Val Phe Asn Gly Leu Ser Ile Leu Ala Ser920 925 930 935TTT GCA TCC AGT GAT GAT CCA TAT CAG GGC CCG AGA GAT ATC ATA TCA 3185Phe Ala Ser Ser Asp Asp Pro Tyr Gln Gly Pro Arg Asp Ile Ile Ser940 945 950CCT GAA CTG ATG GCT GAT TAT TTA CAA CCC AAA TTG TTG GGC ATT TTG 3233Pro Glu Leu Met Ala Asp Tyr Leu Gln Pro Lys Leu Leu Gly Ile Leu955 960 965GCT TTT TTT AAC ATG CAG TTA CTG AGC TCT AGT GTT GGC ATT GAA GAT 3281Ala Phe Phe Asn Met Gln Leu Leu Ser Ser Ser Val Gly Ile Glu Asp970 975 980AAG AAA ATG GCC TTG AAC AGT TTG ATG TCT TTG ATG AAG TTA ATG GGA 3329Lys Lys Met Ala Leu Asn Ser Leu Met Ser Leu Met Lys Leu Met Gly985 990 995CCC AAA CAT GTC AGT TCT GTG AGG GTG AAG ATG ATG ACC ACA CTG AGA 3377Pro Lys His Val Ser Ser Val Arg Val Lys Met Met Thr Thr Leu Arg1000100510101015ACT GGC CTT CGA TTC AAG GAT GAT TTT CCT GAA TTG TGT TGC AGA GCT 3425Thr Gly Leu Arg Phe Lys Asp Asp Phe Pro Glu Leu Cys Cys Arg Ala102010251030TGG GAC TGC TTT GTT CGC TGC CTG GAT CAT GCT TGT CTG GGC TCC CTT 3473Trp Asp Cys Phe Val Arg Cys Leu Asp His Ala Cys Leu Gly Ser Leu103510401045CTC AGT CAT GTA ATA GTA GCT TTG TTA CCT CTT ATA CAC ATC CAG CCT 5521Leu Ser His Val Ile Val Ala Leu Leu Pro Leu Ile His Ile Gln Pro105010551060AAA GAA ACT GCA GCT ATC TTC CAC TAC CTC ATA ATT GAA AAC AGG GAT 3569Lys Glu Thr Ala Ala Ile Phe His Tyr Leu Ile Ile Glu Asn Arg Asp106510701075GCT GTG CAA GAT TTT CTT CAT GAA ATA TAT TTT TTA CCT GAT CAT CCA 3617Ala Val Gln Asp Phe Leu His Glu Ile Tyr Phe Leu Pro Asp His Pro1080108510901095GAA TTA AAA AAG ATA AAA GCC GTT CTC CAG GAA TAC AGA AAG GAG ACC 3665Glu Leu Lys Lys Ile Lys Ala Val Leu Gln Glu Tyr Arg Lys Glu Thr110011051110TCT GAG AGC ACT GAT CTT CAG ACA ACT CTT CAG CTC TCT ATG AAG GCC 3713Ser Glu Ser Thr Asp Leu Gln Thr Thr Leu Gln Leu Ser Met Lys Ala111511201125ATT CAA CAT GAA AAT GTC GAT GTT CGT ATT CAT GCT CTT ACA AGC TTG 3762Ile Gln His Glu Asn Val Asp Val Arg Ile His Ala Leu Thr Ser Leu113011351140AAG GAA ACC TTG TAT AAA AAT CAG GAA AAA CTG ATA AAG TAT GCA ACA 3809Lys Glu Thr Leu Tyr Lys Asn Gln Glu Lys Leu Ile Lys Tyr Ala Thr114511501155GAC AGT GAA ACA GTA GAA CCT ATT ATC TCA CAG TTG GTG ACA GTG CTT 3857Asp Ser Glu Thr Val Glu Pro Ile Ile Ser Gln Leu Val Thr Val Leu1160116511701175TTG AAA GGT TGC CAA GAT GCA AAC TCT CAA GCT CGG TTG CTC TGT GGG 3905Leu Lys Gly Cys Gln Asp Ala Asn Ser Gln Ala Arg Leu Leu Cys Gly118011851190GAA TGT TTA GGG GAA TTG GGG GCG ATA GAT CCA GGT CGA TTA GAT TTC 3953Glu Cys Leu Gly Glu Leu Gly Ala Ile Asp Pro Gly Arg Leu Asp Phe119512001205TCA ACA ACT GAA ACT CAA GGA AAA GAT TTT ACA TTT GTG ACT GGA GTA 4001Ser Thr Thr Glu Thr Gln Gly Lys Asp Phe Thr Phe Val Thr Gly Val121012151220GAA GAT TCA AGC TTT GCC TAT GGA TTA TTG ATG GAG CTA ACA AGA GCT 4049Glu Asp Ser Ser Phe Ala Tyr Gly Leu Leu Met Glu Leu Thr Arg Ala122512301235TAC CTT GCG TAT GCT GAT AAT AGC CGA GCT CAA GAT TCA GCT GCC TAT 4097Tyr Leu Ala Tyr Ala Asp Asn Ser Arg Ala Gln Asp Ser Ala Ala Tyr1240124512501255GCC ATT CAG GAG TTG CTT TCT ATT TAT GAC TGT AGA GAG ATG GAG ACC 4145Ala Ile Gln Glu Leu Leu Ser Ile Tyr Asp Cys Arg Glu Met Glu Thr126012651270AAC GGC CCA GGT CAC CAA TTG TGG AGG AGA TTT CCT GAG CAT GTT CGG 4193Asn Gly Pro Gly His Gln Leu Trp Arg Arg Phe Pro Glu His Val Arg127512801285GAA ATA CTA GAA CCT CAT CTA AAT ACC AGA TAC AAG AGT TCT CAG AAG 4241Glu Ile Leu Glu Pro His Leu Asn Thr Arg Tyr Lys Ser Ser Gln Lys129012951300TCA ACC GAT TGG TCT GGA GTA AAG AAG CCA ATT TAC TTA AGT AAA TTG 4289Ser Thr Asp Trp Ser Gly Val Lys Lys Pro Ile Tyr Leu Ser Lys Leu130513101315GGT AGT AAC TTT GCA GAA TGG TCA GCA TCT TGG GCA GGT TAT CTT ATT 4337Gly Ser Asn Phe Ala Glu Trp Ser Ala Ser Trp Ala Gly Tyr Leu Ile1320132513301335ACA AAG GTT CGA CAT GAT CTT GCC AGT AAA ATT TTC ACC TGC TGT AGC 4385Thr Lys Val Arg His Asp Leu Ala Ser Lys Ile Phe Thr Cys Cys Ser134013451350ATT ATG ATG AAG CAT GAT TTC AAA GTG ACC ATC TAT CTT CTT CCA CAT 4433Ile Met Met Lys His Asp Phe Lys Val Thr Ile Tyr Leu Leu Pro His135513601365ATT CTG GTG TAT GTC TTA CTG GGT TGT AAT CAA GAA GAT CAG CAG GAG 4481Ile Leu Val Tyr Val Leu Leu Gly Cys Asn Gln Glu Asp Gln Gln Glu137013751380GTT TAT GCA GAA ATT ATG GCA GTT CTA AAG CAT GAC GAT CAG CAT ACC 4529Val Tyr Ala Glu Ile Met Ala Val Leu Lys His Asp Asp Gln His Thr138513901395ATA AAT ACC CAA GAC ATT GCA TCT GAT CTG TGT CAA CTC AGT ACA CAG 4577Ile Asn Thr Gln Asp Ile Ala Ser Asp Leu Cys Gln Leu Ser Thr Gln1400140514101415ACT GTG TTC TCC ATG CTT GAC CAT CTC ACA CAG TGG GCA AGG CAC AAA 4625Thr Val Phe Ser Met Leu Asp His Leu Thr Gln Trp Ala Arg His Lys142014251430TTT CAG GCA CTG AAA GCT GAG AAA TGT CCA CAC AGC AAA TCA AAC AGA 4673Phe Gln Ala Leu Lys Ala Glu Lys Cys Pro His Ser Lys Ser Asn Arg143514401445AAT AAG GTA GAC TCA ATG GTA TCT ACT GTG GAT TAT GAA GAC TAT CAG 4721Asn Lys Val Asp Ser Met Val Ser Thr Val Asp Tyr Glu Asp Tyr Gln145014551460AGT GTA ACC CGT TTT CTA GAC CTC ATA CCC CAG GAT ACT CTG GCA GTA 4769Ser Val Thr Arg Phe Leu Asp Leu Ile Pro Gln Asp Thr Leu Ala Val146514701475GCT TCC TTT CGC TCC AAA GCA TAC ACA CGA GCT GTA ATG CAC TTT GAA 4617Ala Ser Phe Arg Ser Lys Ala Tyr Thr Arg Ala Val Met His Phe Glu1480148514901495TCA TTT ATT ACA GAA AAG AAG CAA AAT ATT CAG GAA CAT CTT GGA TTT 4865Ser Phe Ile Thr Glu Lys Lys Gln Asn Ile Gln Glu His Leu Gly Phe150015051510TTA CAG AAA TTG TAT GCT GCT ATG CAT GAA CCT GAT GGA GTG GCC GGA 4913Leu Gln Lys Leu Tyr Ala Ala Met His Glu Pro Asp Gly Val Ala Gly151515201525GTC AGT GCA ATT AGA AAG GCA GAA CCA TCT CTA AAA GAA CAG ATC CTT 4961Val Ser Ala Ile Arg Lys Ala Glu Pro Ser Leu Lys Glu Gln Ile Leu153015351540GAA CAT GAA AGC CTT GGC TTG CTG AGG GAT GCC ACT GCT TGT TAT GAC 5009Glu His Glu Ser Leu Gly Leu Leu Arg Asp Ala Thr Ala Cys Tyr Asp154515501555AGG GCT ATT CAG CTA GAA CCA GAC CAG ATC ATT CAT TAC CAT GGT GTA 5057Arg Ala Ile Gln Leu Glu Pro Asp Gln Ile Ile His Tyr His Gly Val1560156515701575GTA AAG TCC ATG TTA GGT CTT GGT CAG CTG TCT ACT GTT ATC ACT CAG 5105Val Lys Ser Met Leu Gly Leu Gly Gln Leu Ser Thr Val Ile Thr Gln158015851590GTG AAT GGA GTG CAT GCT AAC AGG TCC GAG TGG ACA GAT GAA TTA AAC 5153Val Asn Gly Val His Ala Asn Arg Ser Glu Trp Thr Asp Glu Leu Asn159516001605ACG TAC AGA GTG GAA GCA GCT TGG AAA TTG TCA CAG TGG GAT TTG GTG 5201Thr Tyr Arg Val Glu Ala Ala Trp Lys Leu Ser Gln Trp Asp Leu Val161016151620GAA AAC TAT TTG GCA GCA GAT GGA AAA TCT ACA ACA TGG AGT GTC AGA 5245Glu Asn Tyr Leu Ala Ala Asp Gly Lys Ser Thr Thr Trp Ser Val Arg162516301635CTG GGA CAG CTA TTA TTA TCA GCC AAA AAA AGA GAT ATC ACA GCT TTT 5297Leu Gly Gln Leu Leu Leu Ser Ala Lys Lys Arg Asp Ile Thr Ala Phe1640164516501655TAT GAC TCA CTG AAA CTA GTG AGA GCA GAA CAA ATT GTA CCT CTT TCA 5345Tyr Asp Ser Leu Lys Leu Val Arg Ala Glu Gln Ile Val Pro Leu Ser166016651670GCT GCA AGC TTT GAA AGA GGC TCC TAC CAA CGA GGA TAT GAA TAT ATT 5393Ala Ala Ser Phe Glu Arg Gly Ser Tyr Gln Arg Gly Tyr Glu Tyr Ile167516801685GTG AGA TTG CAC ATG TTA TGT GAG TTG GAG CAT AGC ATC AAA CCA CTT 5441Val Arg Leu His Met Leu Cys Glu Leu Glu His Ser Ile Lys Pro Leu169016951700TTC CAG CAT TCT CCA GGT GAC AGT TCT CAA GAA GAT TCT CTA AAC TGG 5489Phe Gln His Ser Pro Gly Asp Ser Ser Gln Glu Asp Ser Leu Asn Trp170517101715GTA GCT CGA CTA GAA ATG ACC CAG AAT TCC TAC AGA GCC AAG GAG CCT 5537Val Ala Arg Leu Glu Met Thr Gln Asn Ser Tyr Arg Ala Lys Glu Pro1720172517301735ATC CTG GCT CTC CGG AGG GCT TTA CTA AGC CTC AAC AAA AGA CCA GAT 5585Ile Leu Ala Leu Arg Arg Ala Leu Leu Ser Leu Asn Lys Arg Pro Asp174017451750TAC AAT GAA ATG GTT GGA GAA TGC TGG CTG CAG AGT GCC AGG GTA GCT 5633Tyr Asn Glu Met Val Gly Glu Cys Trp Leu Gln Ser Ala Arg Val Ala175517601765AGA AAG GCT GGT CAC CAC CAG ACA GCC TAC AAT GCT CTC CTT AAT GCA 5681Arg Lys Ala Gly His His Gln Thr Ala Tyr Asn Ala Leu Leu Asn Ala177017751780GGG GAA TCA CGA CTC GCT GAA CTG TAC GTG GAA AGG GCA AAG TGG CTC 5729Gly Glu Ser Arg Leu Ala Glu Leu Tyr Val Glu Arg Ala Lys Trp Leu178517901795TGG TCC AAG GGT GAT GTT CAC CAG GCA CTA ATT GTT CTT CAA AAA GGT 5777Trp Ser Lys Gly Asp Val His Gln Ala Leu Ile Val Leu Gln Lys Gly1800180518101815GTT GAA TTA TGT TTT CCT GAA AAT GAA ACC CCA CCT GAG GGT AAG AAC 5825Val Glu Leu Cys Phe Pro Glu Asn Glu Thr Pro Pro Glu Gly Lys Asn182018251830ATG TTA ATC CAT GGT CGA GCT ATG CTA CTA GTG GGC CGA TTT ATG GAA 5873Met Leu Ile His Gly Arg Ala Met Leu Leu Val Gly Arg Phe Met Glu183518401845GAA ACA GCT AAC TTT GAA AGC AAT GCA ATT ATG AAA AAA TAT AAG GAT 5921Glu Thr Ala Asn Phe Glu Ser Asn Ala Ile Met Lys Lys Tyr Lys Asp185018551860GTG ACC GCG TGC CTG CCA GAA TGG GAG GAT GGG CAT TTT TAC CTT GCC 5963Val Thr Ala Cys Leu Pro Glu Trp Glu Asp Gly His Phe Tyr Leu Ala186518701875AAG TAC TAT GAC AAA TTG ATG CCC ATG GTC ACA GAC AAC AAA ATG GAA 6017Lys Tyr Tyr Asp Lys Leu Met Pro Met Val Thr Asp Asn Lys Met Glu1880188518901895AAG CAA GGT GAT CTC ATC CGG TAT ATA GTT CTT CAT TTT GGC AGA TCT 6065Lys Gln Gly Asp Leu Ile Arg Tyr Ile Val Leu His Phe Gly Arg Ser190019051910CTA CAA TAT GGA AAT CAG TTC ATA TAT CAG TCA ATG CCA CGA ATG TTA 6113Leu Gln Tyr Gly Asn Gln Phe Ile Tyr Gln Ser Met Pro Arg Met Leu191519201925ACT CTA TGG CTT GAT TAT GGT ACA AAG GCA TAT GAA TGG GAA AAA GCT 6161Thr Leu Trp Leu Asp Tyr Gly Thr Lys Ala Tyr Glu Trp Glu Lys Ala193019351940GGC CGC TCC GAT CGT GTA CAA ATG AGG AAT GAT TTG GGT AAA ATA AAC 6209Gly Arg Ser Asp Arg Val Gln Met Arg Asn Asp Leu Gly Lys Ile Asn194519501955AAG GTT ATC ACA GAG CAT ACA AAC TAT TTA GCT CCA TAT CAA TTT TTG 6257Lys Val Ile Thr Glu His Thr Asn Tyr Leu Ala Pro Tyr Gln Phe Leu1960196519701975ACT GCT TTT TCA CAA TTG ATC TCT CGA ATT TGT CAT TCT CAC GAT GAA 6305Thr Ala Phe Ser Gln Leu Ile Ser Arg Ile Cys His Ser His Asp Glu198019851990GTT TTT GTT GTC TTG ATG GAA ATA ATA GCC AAA GTA TTT CTA GCC TAT 6353Val Phe Val Val Leu Met Glu Ile Ile Ala Lys Val Phe Leu Ala Tyr199520002005CCT CAA CAA GCA ATG TGG ATG ATG ACA GCT GTG TCA AAG TCA TCT TAT 6401Pro Gln Gln Ala Met Trp Met Met Thr Ala Val Ser Lys Ser Ser Tyr201020152020CCC ATG CGT GTG AAC AGA TGC AAG GAA ATC CTC AAT AAA GCT ATT CAT 6449Pro Met Arg Val Asn Arg Cys Lys Glu Ile Leu Asn Lys Ala Ile His202520302035ATG AAA AAA TCC TTA GAG AAG TTT GTT GGA GAT GCA ACT CGC CTA ACA 6497Met Lys Lys Ser Leu Glu Lys Phe Val Gly Asp Ala Thr Arg Leu Thr2040204520502055GAT AAG CTT CTA GAA TTG TGC AAT AAA CCG GTG GAA ATT CTT GCT TCT 6545Asp Lys Leu Leu Glu Leu Cys Asn Lys Pro Val Glu Ile Leu Ala Ser206020652070CTT CAG AAA CCA AAG AAG ATT TCT TTA AAA GGC TCA GAT GGA AAG TTC 6593Leu Gln Lys Pro Lys Lys Ile Ser Leu Lys Gly Ser Asp Gly Lys Phe207520802085TAC ATC ATG ATG TGT AAG CCA AAA GAT GAC CTG AGA AAG GAT TGT AGA 6641Tyr Ile Met Met Cys Lys Pro Lys Asp Asp Leu Arg Lys Asp Cys Arg209020952100CTA ATG GAA TTC AAT TCC TTG ATT AAT AAG TGC TTA AGA AAA GAT GCA 6689Leu Met Glu Phe Asn Ser Leu Ile Asn Lys Cys Leu Arg Lys Asp Ala210521102115GAG TCT CGT AGA AGA GAA CTT CAT ATT CGA ACA TAT GCA GTT ATT CCA 6737Glu Ser Arg Arg Arg Glu Leu His Ile Arg Thr Tyr Ala Val Ile Pro2120212521302135CTA AAT GAT GAA TGT GGG ATT ATT GAA TGG GTG AAC AAC ACT GCT GGT 6785Leu Asn Asp Glu Cys Gly Ile Ile Glu Trp Val Asn Asn Thr Ala Gly214021452150TTG AGA CCT ATT CTG ACC AAA CTA TAT AAA GAA AAG GGA GTG TAT ATG 6833Leu Arg Pro Ile Leu Thr Lys Leu Tyr Lys Glu Lys Gly Val Tyr Met215521602165ACA GGA AAA GAA CTT CGC CAG TGT ATG CTA CCA AAG TCA GCA GCT TTA 6881Thr Gly Lys Glu Leu Arg Gln Cys Met Leu Pro Lys Ser Ala Ala Leu217021752180TCT GAA AAA CTC AAA GTA TTC CGA GAA TTT CTC CTG CCC AGG CAT CCT 6929Ser Glu Lys Leu Lys Val Phe Arg Glu Phe Leu Leu Pro Arg His Pro218521902195CCT ATT TTT CAT GAG TGG TTT CTG AGA ACA TTC CCT GAT CCT ACA TCA 6977Pro Ile Phe His Glu Trp Phe Leu Arg Thr Phe Pro Asp Pro Thr Ser2200220522102215TGG TAC AGT AGT AGA TCA GCT TAC TGC CGT TCC ACT GCA GTA ATG TCA 7025Trp Tyr Ser Ser Arg Ser Ala Tyr Cys Arg Ser Thr Ala Val Met Ser222022252230ATG GTT GGT TAT ATT CTG GGG CTT GGA GAC CGT CAT GGT GAA AAT ATT 7073Met Val Gly Tyr Ile Leu Gly Leu Gly Asp Arg His Gly Glu Asn Ile223522402245CTC TTT GAT TCT TTG ACT GGT GAA TGC GTA CAT GTA GAT TTC AAT TGT 7121Leu Phe Asp Ser Leu Thr Gly Glu Cys Val His Val Asp Phe Asn Cys225022552260CTT TTC AAT AAG GGA GAA ACC TTT GAA GTT CCA GAA ATT GTG CCA TTT 7169Leu Phe Asn Lys Gly Glu Thr Phe Glu Val Pro Glu Ile Val Pro Phe226522702275CGC CTG ACT CAT AAT ATG GTT AAT GGA ATG GGT CCT ATG GGA ACA GAG 7217Arg Leu Thr His Asn Met Val Asn Gly Met Gly Pro Met Gly Thr Glu2280228522902295GGT CTT TTT CGA AGA GCA TGT GAA GTT ACA ATG AGG CTG ATG CGT GAT 7265Gly Leu Phe Arg Arg Ala Cys Glu Val Thr Met Arg Leu Met Arg Asp230023052310CAG CGA GAG CCT TTA ATG AGT GTC TTA AAG ACT TTT CTA CAT GAT CCT 7313Gln Arg Glu Pro Leu Met Ser Val Leu Lys Thr Phe Leu His Asp Pro231523202325CTT GTG GAA TGG AGT AAA CCA GTG AAA GGG CAT TCC AAA GCG CCA CTG 7361Leu Val Glu Trp Ser Lys Pro Val Lys Gly His Ser Lys Ala Pro Leu233023352340AAT GAA ACT GGA GAA GTT GTC AAT GAA AAG GCC AAG ACC CAT GTT CTT 7409Asn Glu Thr Gly Glu Val Val Asn Glu Lys Ala Lys Thr His Val Leu234523502355GAC ATT GAG CAG CGA CTA CAA GGT GTA ATC AAG ACT CGA AAT AGA GTG 7457Asp Ile Glu Gln Arg Leu Gln Gly Val Ile Lys Thr Arg Asn Arg Val2360236523702375ACA GGA CTG CCG TTA TCT ATT GAA GGA CAT GTG CAT TAC CTT ATA CAA 7505Thr Gly Leu Pro Leu Ser Ile Glu Gly His Val His Tyr Leu Ile Gln238023852390GAA GCT ACT GAT GAA AAC TTA CTA TGC CAG ATG TAT CTT GGT TGG ACT 7553Glu Ala Thr Asp Glu Asn Leu Leu Cys Gln Met Tyr Leu Gly Trp Thr239524002405CCA TAT ATG TGAAATGAAA TTATGTAAAA GAATATGTTA ATAATCTAAA 7602Pro Tyr Met2410AGTAAAAAAA AAAAAAAAAA AA 7624(2)SEQ ID NO31的说明(i)序列特征(A)长度2410个氨基酸(B)类型氨基酸(D)拓扑结构线性(ii)分子类型蛋白(xi)序列描述SEQ ID NO31Met Gly His Ala Val Glu Trp Pro Val Val Met Ser Arg Phe Leu Ser1 5 10 15Gln Leu Asp Glu His Met Gly Tyr Leu Gln Ser Ala Pro Leu Gln Leu20 25 30Met Ser Met Gln Asn Leu Glu Phe Ile Glu Val Thr Leu Leu Met Val35 40 45Leu Thr Arg Ile Ile Ala Ile Val Phe Phe Arg Arg Gln Glu Leu Leu50 55 60Leu Trp Gln Ile Gly Cys Val Leu Leu Glu Tyr Gly Ser Pro Lys Ile65 70 75 80Lys Ser Leu Ala Ile Ser Phe Leu Thr Glu Leu Phe Gln Leu Gly Gly85 90 95Leu Pro Ala Gln Pro Ala Ser Thr Phe Phe Ser Ser Phe Leu Glu Leu100 105 110Leu Lys His Leu Val Glu Met Asp Thr Asp Gln Leu Lys Leu Tyr Glu115 120 125Glu Pro Leu Ser Lys Leu Ile Lys Thr Leu Phe Pro Phe Glu Ala Glu130 135 140Ala Tyr Arg Asn Ile Glu Pro Val Tyr Leu Asn Met Leu Leu Glu Lys145 150 155 160Leu Cys Val Met Phe Glu Asp Gly Val Leu Met Arg Leu Lys Ser Asp165 170 175Leu Leu Lys Ala Ala Leu Cys His Leu Leu Gln Tyr Phe Leu Lys Phe180 185 190Val Pro Ala Gly Tyr Glu Ser Ala Leu Gln Val Arg Lys Val Tyr Val195 200 205Arg Asn Ile Cys Lys Ala Leu Leu Asp Val Leu Gly Ile Glu Val Asp210 215 220Ala Glu Tyr Leu Leu Gly Pro Leu Tyr Ala Ala Leu Lys Met Glu Ser225 230 235 240Met Glu Ile Ile Glu Glu Ile Gln Cys Gln Thr Gln Gln Glu Asn Leu245 250 255Ser Ser Asn Ser Asp Gly Ile Ser Pro Lys Arg Arg Arg Leu Ser Ser260 265 270Ser Leu Asn Pro ser Lys Arg Ala Pro Lys Gln Thr Glu Glu Ile Lys275 280 285His Val Asp Met Asn Gln Lys Ser Ile Leu Trp Ser Ala Leu Lys Gln290 295 300Lys Ala Glu Ser Leu Gln Ile Ser Leu Glu Tyr Ser Gly Leu Lys Asn305 310 315 320Pro Val Ile Glu Met Leu Glu Gly Ile Ala Val Val Leu Gln Leu Thr325 330 335Ala Leu Cys Thr Val His Cys Ser His Gln Asn Met Asn Cys Arg Thr340 345 350Phe Lys Asp Cys Gln His Lys Ser Lys Lys Lys Pro Ser Val Val Ile355 360 365Thr Trp Met Ser Leu Asp Phe Tyr Thr Lys Val Leu Lys Ser Cys Arg370 375 380Ser Leu Leu Glu Ser Val Gln Lys Leu Asp Leu Glu Ala Thr Ile Asp385 390 395 400Lys Val Val Lys Ile Tyr Asp Ala Leu Ile Tyr Met Gln Val Asn Ser405 410 415Ser Phe Glu Asp His Ile Leu Glu Asp Leu Cys Gly Met Leu Ser Leu420 425 430Pro Trp Ile Tyr Ser His Ser Asp Asp Gly Cys Leu Lys Leu Thr Thr435 440 445Phe Ala Ala Asn Leu Leu Thr Leu Ser Cys Arg Ile Ser Asp Ser Tyr450 455 460Ser Pro Gln Ala Gln Ser Arg Cys Val Phe Leu Leu Thr Leu Phe Pro465 470 475 480Arg Arg Ile Phe Leu Glu Trp Arg Thr Ala Val Tyr Asn Trp Ala Leu485 490 495Gln Ser Ser His Glu Val Ile Arg Ala Ser Cys Val Ser Gly Phe Phe500 505 510Ile Leu Leu Gln Gln Gln Asn Ser Cys Asn Arg Val Pro Lys Ile Leu515 520 525Ile Asp Lys Val Lys Asp Asp Ser Asp Ile Val Lys Lys Glu Phe Ala530 535 540Ser Ile Leu Gly Gln Leu Val Cys Thr Leu His Gly Met Phe Tyr Leu545 550 555 560Thr Ser Ser Leu Thr Glu Pro Phe Ser Glu His Gly His Val Asp Leu565 570 575Phe Cys Arg Asn Leu Lys Ala Thr Ser Gln His Glu Cys Ser Ser Ser580 585 590Gln Leu Lys Ala Ser Val Cys Lys Pro Phe Leu Phe Leu Leu Lys Lys595 600 605Lys Ile Pro Ser Pro Val Lys Leu Ala Phe Ile Asp Asn Leu His His610 615 620Leu Cys Lys His Leu Asp Phe Arg Glu Asp Glu Thr Asp Val Lys Ala625 630 635 640Val Leu Gly Thr Leu Leu Asn Leu Met Glu Asp Pro Asp Lys Asp Val645 650 655Arg Val Ala Phe Ser Gly Asn Ile Lys His Ile Leu Glu Ser Leu Asp660 665 670Ser Glu Asp Gly Phe Ile Lys Glu Leu Phe Val Leu Arg Met Lys Glu675 680 685Ala Tyr Thr His Ala Gln Ile Ser Arg Asn Asn Glu Leu Lys Asp Thr690 695 700Leu Ile Leu Thr Thr Gly Asp Ile Gly Arg Ala Ala Lys Gly Asp Leu705 710 715 720Val Pro Phe Ala Leu Leu His Leu Leu His Cys Leu Leu Ser Lys Ser725 730 735Ala Ser Val Ser Gly Ala Ala Tyr Thr Glu Ile Arg Ala Leu Val Ala740 745 750Ala Lys Ser Val Lys Leu Gln Ser Phe Phe Ser Gln Tyr Lys Lys Pro755 760 765Ile Cys Gln Phe Leu Val Glu Ser Leu His Ser Ser Gln Met Thr Ala770 775 780Leu Pro Asn Thr Pro Cys Gln Asn Ala Asp Val Arg Lys Gln Asp Val785 790 795 800Ala His Gln Arg Glu Met Ala Leu Asn Thr Leu Ser Glu Ile Ala Asn805 810 815Val Phe Asp Phe Pro Asp Leu Asn Arg Phe Leu Thr Arg Thr Leu Gln820 825 830Val Leu Leu Pro Asp Leu Ala Ala Lys Ala Ser Pro Ala Ala Ser Ala835 840 845Leu Ile Arg Thr Leu Gly Lys Gln Leu Asn Val Asn Arg Arg Glu Ile850 855 860Leu Ile Asn Asn Phe Lys Tyr Ile Phe Ser His Leu Val Cys Ser Cys865 870 875 880Ser Lys Asp Glu Leu Glu Arg Ala Leu His Tyr Leu Lys Asn Glu Thr885 890 895Glu Ile Glu Leu Gly Ser Leu Leu Arg Gln Asp Phe Gln Gly Leu His900 905 910Asn Glu Leu Leu Leu Arg Ile Gly Glu His Tyr Gln Gln Val Phe Asn915 920 925Gly Leu Ser Ile Leu Ala Ser Phe Ala Ser Ser Asp Asp Pro Tyr Gln930 935 940Gly Pro Arg Asp Ile Ile Ser Pro Glu Leu Met Ala Asp Tyr Leu Gln945 950 955 960Pro Lys Leu Leu Gly Ile Leu Ala Phe Phe Asn Met Gln Leu Leu Ser965 970 975Ser Ser Val Gly Ile Glu Asp Lys Lys Met Ala Leu Asn Ser Leu Met980 985 990Ser Leu Met Lys Leu Met Gly Pro Lys His Val Ser Ser Val Arg Val995 10001005Lys Met Met Thr Thr Leu Arg Thr Gly Leu Arg Phe Lys Asp Asp Phe101010151020Pro Glu Leu Cys Cys Arg Ala Trp Asp Cys Phe Val Arg Cys Leu Asp1025103010351040His Ala Cys Leu Gly Ser Leu Leu Ser His Val Ile Val Ala Leu Leu104510501055Pro Leu Ile His Ile Gln Pro Lys Glu Thr Ala Ala Ile Phe His Tyr106010651070Leu Ile Ile Glu Asn Arg Asp Ala Val Gln Asp Phe Leu His Glu Ile107510801085Tyr Phe Leu Pro Asp His Pro Glu Leu Lys Lys Ile Lys Ala Val Leu109010951100Gln Glu Tyr Arg Lys Glu Thr Ser Glu Ser Thr Asp Leu Gln Thr Thr1105111011151120Leu Gln Leu Ser Met Lys Ala Ile Gln His Glu Asn Val Asp Val Arg112511301135Ile His Ala Leu Thr Ser Leu Lys Glu Thr Leu Tyr Lys Asn Gln Glu114011451150Lys Leu Ile Lys Tyr Ala Thr Asp Ser Glu Thr Val Glu Pro Ile Ile115511601165Ser Gln Leu Val Thr Val Leu Leu Lys Gly Cys Gln Asp Ala Asn Ser117011751180Gln Ala Arg Leu Leu Cys Gly Glu Cys Leu Gly Glu Leu Gly Ala Ile1185119011951200Asp Pro Gly Arg Leu Asp Phe Ser Thr Thr Glu Thr Gln Gly Lys Asp120512101215Phe Thr Phe Val Thr Gly Val Glu Asp Ser Ser Phe Ala Tyr Gly Leu122012251230Leu Met Glu Leu Thr Arg Ala Tyr Leu Ala Tyr Ala Asp Asn Ser Arg123512401245Ala Gln Asp Ser Ala Ala Tyr Ala Ile Gln Glu Leu Leu Ser Ile Tyr125012551260Asp Cys Arg Glu Met Glu Thr Asn Gly Pro Gly His Gln Leu Trp Arg1265127012751280Arg Phe Pro Glu His Val Arg Glu Ile Leu Glu Pro His Leu Asn Thr128512901295Arg Tyr Lys Ser Ser Gln Lys Ser Thr Asp Trp Ser Gly Val Lys Lys130013051310Pro Ile Tyr Leu Ser Lys Leu Gly Ser Asn Phe Ala Glu Trp Ser Ala131513201325Ser Trp Ala Gly Tyr Leu Ile Thr Lys Val Arg His Asp Leu Ala Ser133013351340Lys Ile Phe Thr Cys Cys Ser Ile Met Met Lys His Asp Phe Lys Val1345135013551360Thr Ile Tyr Leu Leu Pro His Ile Leu Val Tyr Val Leu Leu Gly Cys136513701375Asn Gln Glu Asp Gln Gln Glu Val Tyr Ala Glu Ile Met Ala Val Leu138013851390Lys His Asp Asp Gln His Thr Ile Asn Thr Gln Asp Ile Ala Ser Asp139514001405Leu Cys Gln Leu Ser Thr Gln Thr Val Phe Ser Met Leu Asp His Leu141014151420Thr Gln Trp Ala Arg His Lys Phe Gln Ala Leu Lys Ala Glu Lys Cys1425143014351440Pro His Ser Lys Ser Asn Arg Asn Lys Val Asp Ser Met Val Ser Thr144514501455Val Asp Tyr Glu Asp Tyr Gln Ser Val Thr Arg Phe Leu Asp Leu Ile146014651470Pro Gln Asp Thr Leu Ala Val Ala Ser Phe Arg Ser Lys Ala Tyr Thr147514801485Arg Ala Val Met His Phe Glu Ser Phe Ile Thr Glu Lys Lys Gln Asn149014951500Ile Gln Glu His Leu Gly Phe Leu Gln Lys Leu Tyr Ala Ala Met His1505151015151520Glu Pro Asp Gly Val Ala Gly Val Ser Ala Ile Arg Lys Ala Glu Pro152515301535Ser Leu Lys Glu Gln Ile Leu Glu His Glu Ser Leu Gly Leu Leu Arg154015451550Asp Ala Thr Ala Cys Tyr Asp Arg Ala Ile Gln Leu Glu Pro Asp Gln155515601565Ile Ile His Tyr His Gly Val Val Lys Ser Met Leu Gly Leu Gly Gln157015751580Leu Ser Thr Val Ile Thr Gln Val Asn Gly Val His Ala Asn Arg Ser1585159015951500Glu Trp Thr Asp Glu Leu Asn Thr Tyr Arg Val Glu Ala Ala Trp Lys160516101615Leu Ser Gln Trp Asp Leu Val Glu Asn Tyr Leu Ala Ala Asp Gly Lys162016251630Ser Thr Thr Trp Ser Val Arg Leu Gly Gln Leu Leu Leu Ser Ala Lys163516401645Lys Arg Asp Ile Thr Ala Phe Tyr Asp Ser Leu Lys Leu Val Arg Ala165016551660Glu Gln Ile Val Pro Leu Ser Ala Ala Ser Phe Glu Arg Gly Ser Gyr1665167016751680Gln Arg Gly Tyr Glu Tyr Ile Val Arg Leu His Met Leu Cys Glu Leu168516901695Glu His Ser Ile Lys Pro Leu Phe Gln His Ser Pro Gly Asp Ser Ser170017051710Gln Glu Asp Ser Leu Asn Trp Val Ala Arg Leu Glu Met Thr Gln Asn171517201725Ser Tyr Arg Ala Lys Glu Pro Ile Leu Ala Leu Arg Arg Ala Leu Leu173017351740Ser Leu Asn Lys Arg Pro Asp Tyr Asn Glu Met Val Gly Glu Cys Trp1745175017551760Leu Gln Ser Ala Arg Val Ala Arg Lys Ala Gly His His Gln Thr Ala176517701775Tyr Asn Ala Leu Leu Asn Ala Gly Glu Ser Arg Leu Ala Glu Leu Tyr178017851790Val Glu Arg Ala Lys Trp Leu Trp Ser Lys Gly Asp Val His Gln Ala179518001805Leu Ile Val Leu Gln Lys Gly Val Glu Leu Cys Phe Pro Glu Asn Glu181018151820Thr Pro Pro Glu Gly Lys Asn Met Leu Ile His Gly Arg Ala Met Leu1825183018351840Leu Val Gly Arg Phe Met Glu Glu Thr Ala Asn Phe Glu Ser Asn Ala184518501855Ile Met Lys Lys Tyr Lys Asp Val Thr Ala Cys Leu Pro Glu Trp Glu186018651870Asp Gly His Phe Tyr Leu Ala Lys Tyr Tyr Asp Lys Leu Met Pro Met187518801885Val Thr Asp Asn Lys Met Glu Lys Gln Gly Asp Leu Ile Arg Tyr Ile189018951900Val Leu His Phe Gly Arg Ser Leu Gln Tyr Gly Asn Gln Phe Ile Tyr1905191019151920Gln Ser Met Pro Arg Met Leu Thr Leu Trp Leu Asp Tyr Gly Thr Lys192519301935Ala Tyr Glu Trp Glu Lys Ala Gly Arg Ser Asp Arg Val Gln Met Arg194019451950Asn Asp Leu Gly Lys Ile Asn Lys Val Ile Thr Glu His Thr Asn Tyr195519601965Leu Ala Pro Tyr Gln Phe Leu Thr Ala Phe Ser Gln Leu Ile Ser Arg197019751980Ile Cys His Ser His Asp Glu Val Phe Val Val Leu Met Glu Ile Ile1985199019952000Ala Lys Val Phe Leu Ala Tyr Pro Gln Gln Ala Met Trp Met Met Thr200520102015Ala Val Ser Lys Ser Ser Tyr Pro Met Arg Val Asn Arg Cys Lys Glu202020252030Ile Leu Asn Lys Ala Ile His Met Lys Lys Ser Leu Glu Lys Phe Val203520402045Gly Asp Ala Thr Arg Leu Thr Asp Lys Leu Leu Glu Leu Cys Asn Lys205020552060Pro Val Glu Ile Leu Ala Ser Leu Gln Lys Pro Lys Lys Ile Ser Leu2065207020752080Lys Gly Ser Asp Gly Lys Phe Tyr Ile Met Met Cys Lys Pro Lys Asp208520902095Asp Leu Arg Lys Asp Cys Arg Leu Met Glu Phe Asn Ser Leu Ile Asn210021052110Lys Cys Leu Arg Lys Asp Ala Glu Ser Arg Arg Arg Glu Leu His Ile211521202125Arg Thr Tyr Ala Val Ile Pro Leu Asn Asp Glu Cys Gly Ile Ile Glu213021352140Trp Val Asn Asn Thr Ala Gly Leu Arg Pro Ile Leu Thr Lys Leu Tyr2145215021552160Lys Glu Lys Gly Val Tyr Met Thr Gly Lys Glu Leu Arg Gln Cys Met216521702175Leu Pro Lys Ser Ala Ala Leu Ser Glu Lys Leu Lys Val Phe Arg Glu218021852190Phe Leu Leu Pro Arg His Pro Pro Ile Phe His Glu Trp Phe Leu Arg219522002205Thr Phe Pro Asp Pro Thr Ser Trp Tyr Ser Ser Arg Ser Ala Tyr Cys221022152220Arg Ser Thr Ala Val Met Ser Met Val Gly Tyr Ile Leu Gly Leu Gly2225223022352240Asp Arg His Gly Glu Asn Ile Leu Phe Asp Ser Leu Thr Gly Glu Cys224522502255Val His Val Asp Phe Asn Cys Leu Phe Asn Lys Gly Glu Thr Phe Glu226022652270Val Pro Glu Ile Val Pro Phe Arg Leu Thr His Asn Met Val Asn Gly227522802285Met Gly Pro Met Gly Thr Glu Gly Leu Phe Arg Arg Ala Cys Glu Val229022952300Thr Met Arg Leu Met Arg Asp Gln Arg Glu Pro Leu Met Ser Val Leu2305231023152320Lys Thr Phe Leu His Asp Pro Leu Val Glu Trp Ser Lys Pro Val Lys232523302335Gly His Ser Lys Ala Pro Leu Asn Glu Thr Gly Glu Val Val Asn Glu234023452350Lys Ala Lys Thr His Val Leu Asp Ile Glu Gln Arg Leu Gln Gly Val235523602365Ile Lys Thr Arg Asn Arg Val Thr Gly Leu Pro Leu Ser Ile Glu Gly237023752380His Val His Tyr Leu Ile Gln Glu Ala Thr Asp Glu Asn Leu Leu Cys2385239023952400Gln Met Tyr Leu Gly Trp Thr Pro Tyr Met24052410(2)SEQ ID NO32的说明(i)序列特征(A)长度7502个碱基对(B)类型核苷酸(C)链型单链(D)拓扑结构线性(ii)分子类型cDNA(ix)特征(A)姓名/符号CDS(B)位置1..7440(xi)序列描述SEQ ID NO32ATG GGT CAT GCT GTG GAA TGG CCA GTG GTC ATG AGC CGA TTT TTA AGT 48Met Gly His Ala Val Glu Trp Pro Val Val Met Ser Arg Phe Leu Ser1 5 10 15CAA TTA GAT GAA CAC ATG GGA TAT TTA CAA TCA GCT CCT TTG GAG TTG 96Gln Leu Asp Glu His Met Gly Tyr Leu Gln Ser Ala Pro Leu Gln Leu20 25 30ATG AGT ATG CAA AAT TTA GAA TTT ATT GAA GTC ACT TTA TTA ATG GTT 144Met Ser Met Gln Asn Leu Glu Phe Ile Glu Val Thr Leu Leu Met Val35 40 45CTT ACT CGT ATT ATT GCA ATT GTG TTT TTT AGA AGG CAA GAA CTC TTA 192Leu Thr Arg Ile Ile Ala Ile Val Phe Phe Arg Arg Gln Glu Leu Leu50 55 60CTT TGG CAG ATA GGT TGT GTT CTG CTA GAG TAT GGT AGT CCA AAA ATT 240Leu Trp Gln Ile Gly Cys Val Leu Leu Glu Tyr Gly Ser Pro Lys Ile65 70 75 80AAA TCC CTA GCA ATT AGC TTT TTA ACA GAA CTT TTT CAG CTT GGA GGA 288Lys Ser Leu Ala Ile Ser Phe Leu Thr Glu Leu Phe Gln Leu Gly Gly85 90 95CTA CCA GCA CAA CCA GCT AGC ACT TTT TTC AGC TCA TTT TTG GAA TTA 336Leu Pro Ala Gln Pro Ala Ser Thr Phe Phe Ser Ser Phe Leu Glu Leu100 105 110TTA AAA CAC CTT GTA GAA ATG GAT ACT GAC CAA TTG AAA CTC TAT GAA 384Leu Lys His Leu Val Glu Met Asp Thr Asp Gln Leu Lys Leu Tyr Glu115 120 125GAG CCA TTA TCA AAG CTG ATA AAG ACA CTA TTT CCC TTT GAA GCA GAA 432Glu Pro Leu Ser Lys Leu Ile Lys Thr Leu Phe Pro Phe Glu Ala Glu130 135 140GCT TAT AGA AAT ATT GAA CCT GTC TAT TTA AAT ATG CTG CTG GAA AAA 480Ala Tyr Arg Asn Ile Glu Pro Val Tyr Leu Asn Met Leu Leu Glu Lys145 150 155 160CTC TGT GTC ATG TTT GAA GAC GGT GTG CTC ATG CGG CTT AAG TCT GAT 528Leu Cys Val Met Phe Glu Asp Gly Val Leu Met Arg Leu Lys Ser Asp165 170 175TTG CTA AAA GCA GCT TTG TGC CAT TTA CTG CAG TAT TTC CTT AAA TTT 576Leu Leu Lys Ala Ala Leu Cys His Leu Leu Gln Tyr Phe Leu Lys Phe180 185 190GTG CCA GCT GGG TAT GAA TCT GCT TTA CAA GTC AGG AAG GTC TAT GTG 624Val Pro Ala Gly Tyr Glu Ser Ala Leu Gln Val Arg Lys Val Tyr Val195 200 205AGA AAT ATT TGT AAA GCT CTT TTG GAT GTG CTT GGA ATT GAG GTA GAT 672Arg Asn Ile Cys Lys Ala Leu Leu Asp Val Leu Gly Ile Glu Val Asp210 215 220GCA GAG TAC TTG TTG GGC CCA CTT TAT GCA GCT TTG AAA ATG GAA AGT 720Ala Glu Tyr Leu Leu Gly Pro Leu Tyr Ala Ala Leu Lys Met Glu Ser225 230 235 240ATG GAA ATC ATT GAG GAG ATT CAA TGC CAA ACT CAA CAG GAA AAC CTC 768Met Glu Ile Ile Glu Glu Ile Gln Cys Gln Thr Gln Gln Glu Asn Leu245 250 255AGC AGT AAT AGT GAT GGA ATA TCA CCC AAA AGG CGT CGT CTC AGC TCG 816Ser Ser Asn Ser Asp Gly Ile Ser Pro Lys Arg Arg Arg Leu Ser Ser260 265 270TCT CTA AAC CCT TCT AAA AGA GCA CCA AAA CAG ACT GAG GAA ATT AAA 864Ser Leu Asn Pro Ser Lys Arg Ala Pro Lys Gln Thr Glu Glu Ile Lys275 280 285CAT GTG GAC ATG AAC CAA AAG AGC ATA TTA TGG AGT GCA CTG AAA CAG 912His Val Asp Met Asn Gln Lys Ser Ile Leu Trp Ser Ala Leu Lys Gln290 295 300AAA GCT GAA TCC CTT CAG ATT TCC CTT GAA TAC AGT GGC CTA AAG AAT 960Lys Ala Glu Ser Leu Gln Ile Ser Leu Glu Tyr Ser Gly Leu Lys Asn305 310 315 320CCT GTT ATT GAG ATG TTA GAA GGA ATT GCT GTT GTC TTA CAA CTG ACT 1008Pro Val Ile Glu Met Leu Glu Gly Ile Ala Val Val Leu Gln Leu Thr325 330 335GCT CTG TGT ACT GTT CAT TGT TCT CAT CAA AAC ATG AAC TGC CGT ACT 1056Ala Leu Cys Thr Val His Cys Ser His Gln Asn Met Asn Cys Arg Thr340 345 350TTC AAG GAC TGT CAA CAT AAA TCC AAG AAG AAA CCT TCT GTA GTG ATA 1104Phe Lys Asp Cys Gln His Lys Ser Lys Lys Lys Pro Ser Val Val Ile355 360 365ACT TGG ATG TCA TTG GAT TTT TAC ACA AAA GTG CTT AAG AGC TGT AGA 1152Thr Trp Met Ser Leu Asp Phe Tyr Thr Lys Val Leu Lys Ser Cys Arg370 375 380AGT TTG TTA GAA TCT GTT CAG AAA CTG GAC CTG GAG GCA ACC ATT GAT 1200Ser Leu Leu Glu Ser Val Gln Lys Leu Asp Leu Glu Ala Thr Ile Asp385 390 395 400AAG GTG GTG AAA ATT TAT GAT GCT TTG ATT TAT ATG CAA GTA AAC AGT 1248Lys Val Val Lys Ile Tyr Asp Ala Leu Ile Tyr Met Gln Val Asn Ser405 410 415TCA TTT GAA GAT CAT ATC CTG GAA GAT TTA TGT GGA ATG CTC TCA CTT 1296Ser Phe Glu Asp His Ile Leu Glu Asp Leu Cys Gly Met Leu Ser Leu420 425 430CCA TGG ATT TAT TCC CAT TCT GAT GAT GGC TGT TTA AAG TTG ACC ACA 1344Pro Trp Ile Tyr Ser His Ser Asp Asp Gly Cys Leu Lys Leu Thr Thr435 440 445TTT GCC GCT AAT CTT CTA ACA TTA AGC TGT AGG ATT TCA GAT AGC TAT 1392Phe Ala Ala Asn Leu Leu Thr Leu Ser Cys Arg Ile Ser Asp Ser Tyr450 455 460TCA CCA CAG GCA CAA TCA CGA TGT GTG TTT CTT CTG ACT CTG TTT CCA 1440Ser Pro Gln Ala Gln Ser Arg Cys Val Phe Leu Leu Thr Leu Phe Pro465 470 475 480AGA AGA ATA TTC CTT GAG TGG AGA ACA GCA GTT TAC AAC TGG GCC CTG 1488Arg Arg Ile Phe Leu Glu Trp Arg Thr Ala Val Tyr Asn Trp Ala Leu485 490 495CAG AGC TCC CAT GAA GTA ATC CGG GCT AGT TGT GTT AGT GGA TTT TTT 1536Gln Ser Ser His Glu Val Ile Arg Ala Ser Cys Val Ser Gly Phe Phe500 505 510ATC TTA TTG CAG CAG CAG AAT TCT TGT AAC AGA GTT CCC AAG ATT CTT 1584Ile Leu Leu Gln Gln Gln Asn Ser Cys Asn Arg Val Pro Lys Ile Leu515 520 525ATA GAT AAA GTC AAA GAT GAT TCT GAC ATT GTC AAG AAA GAA TTT GCT 1632Ile Asp Lys Val Lys Asp Asp Ser Asp Ile Val Lys Lys Glu Phe Ala530 535 540TCT ATA CTT GGT CAA CTT GTC TGT ACT CTT CAC GGC ATG TTT TAT CTG 1680Ser Ile Leu Gly Gln Leu Val Cys Thr Leu His Gly Met Phe Tyr Leu545 550 555 560ACA AGT TCT TTA ACA GAA CCT TTC TCT GAA CAC GGA CAT GTG GAC CTC 1728Thr Ser Ser Leu Thr Glu Pro Phe Ser Glu His Gly His Val Asp Leu565 570 575TTC TGT AGG AAC TTG AAA GCC ACT TCT CAA CAT GAA TGT TCA TCT TCT 1776Phe Cys Arg Asn Leu Lys Ala Thr Ser Gln His Glu Cys Ser Ser Ser580 585 590CAA CTA AAA GCT TCT GTC TGC AAG CCA TTC CTT TTC CTA CTG AAA AAA 1824Gln Leu Lys Ala Ser Val Cys Lys Pro Phe Leu Phe Leu Leu Lys Lys595 600 605AAA ATA CCT AGT CCA GTA AAA CTT GCT TTC ATA GAT AAT CTA CAT CAT 1872Lys Ile Pro Ser Pro Val Lys Leu Ala Phe Ile Asp Asn Leu His His610 615 620CTT TGT AAG CAT CTT GAT TTT AGA GAA GAT GAA ACA GAT GTA AAA GCA 1920Leu Cys Lys His Leu Asp Phe Arg Glu Asp Glu Thr Asp Val Lys Ala625 630 635 640GTT CTT GGA ACT TTA TTA AAT TTA ATG GAA GAT CCA GAC AAA GAT GTT 1968Val Leu Gly Thr Leu Leu Asn Leu Met Glu Asp Pro Asp Lys Asp Val645 650 655AGA GTG GCT TTT AGT GGA AAT ATC AAG CAC ATA TTG GAA TCC TTG GAC 2016Arg Val Ala Phe Ser Gly Asn Ile Lys His Ile Leu Glu Ser Leu Asp660 665 670TCT GAA GAT GGA TTT ATA AAG GAG CTT TTT GTC TTA AGA ATG AAG GAA 2064Ser Glu Asp Gly Phe Ile Lys Glu Leu Phe Val Leu Arg Met Lys Glu675 680 685GCA TAT ACA CAT GCC CAA ATA TCA AGA AAT AAT GAG CTG AAG GAT ACC 2112Ala Tyr Thr His Ala Gln Ile Ser Arg Asn Asn Glu Leu Lys Asp Thr690 695 700TTG ATT CTT ACA ACA GGG GAT ATT GGA AGG GCC GCA AAA GGA GAT TTG 2160Leu Ile Leu Thr Thr Gly Asp Ile Gly Arg Ala Ala Lys Gly Asp Leu705 710 715 720GTA CCA TTT GCA CTC TTA CAC TTA TTG CAT TGT TTG TTA TCC AAG TCA 2208Val Pro Phe Ala Leu Leu His Leu Leu His Cys Leu Leu Ser Lys Ser725 730 735GCA TCT GTC TCT GGA GCA GCA TAC ACA GAA ATT AGA GCT CTG GTT GCA 2256Ala Ser Val Ser Gly Ala Ala Tyr Thr Glu Ile Arg Ala Leu Val Ala740 745 750GCT AAA AGT GTT AAA CTG CAA AGT TTT TTC AGC CAG TAT AAG AAA CCC 2304Ala Lys Ser Val Lys Leu Gln Ser Phe Phe Ser Gln Tyr Lys Lys Pro755 760 765ATC TGT CAG TTT TTG GTA GAA TCC CTT CAC TCT AGT CAG ATG ACA GCA 2352Ile Cys Gln Phe Leu Val Glu Ser Leu His Ser Ser Gln Met Thr Ala770 775 780CTT CCG AAT ACT CCA TGC CAG AAT GCT GAC GTG CGA AAA CAA GAT GTG 2400Leu Pro Asn Thr Pro Cys Gln Asn Ala Asp Val Arg Lys Gln Asp Val785 790 795 800GCT CAC CAG AGA GAA ATG GCT TTA AAT ACG TTG TCT GAA ATT GCC AAC 2448Ala His Gln Arg Glu Met Ala Leu Asn Thr Leu Ser Glu Ile Ala Asn805 810 815GTT TTC GAC TTT CCT GAT CTT AAT CGT TTT CTT ACT AGG ACA TTA CAA 2496Val Phe Asp Phe Pro Asp Leu Asn Arg Phe Leu Thr Arg Thr Leu Gln820 825 830GTT CTA CTA CCT GAT CTT GCT GCC AAA GCA AGC CCT GCA GCT TCT GCT 2544Val Leu Leu Pro Asp Leu Ala Ala Lys Ala Ser Pro Ala Ala Ser Ala835 840 845CTC ATT CGA ACT TTA GGA AAA CAA TTA AAT GTC AAT CGT AGA GAG ATT 2592Leu Ile Arg Thr Leu Gly Lys Gln Leu Asn Val Asn Arg Arg Glu Ile850 855 860TTA ATA AAC AAC TTC AAA TAT ATT TTT TCT CAT TTG GTC TGT TCT TGT 2640Leu Ile Asn Asn Phe Lys Tyr Ile Phe Ser His Leu Val Cys Ser Cys865 870 875 880TCC AAA GAT GAA TTA GAA CGT GCC CTT CAT TAT CTG AAG AAT GAA ACA 2688Ser Lys Asp Glu Leu Glu Arg Ala Leu His Tyr Leu Lys Asn Glu Thr885 890 895GAA ATT GAA CTG GGG AGC CTG TTG AGA CAA GAT TTC CAA GGA TTG CAT 2736Glu Ile Glu Leu Gly Ser Leu Leu Arg Gln Asp Phe Gln Gly Leu His900 905 910AAT GAA TTA TTG CTG CGT ATT GGA GAA CAC TAT CAA CAG GTT TTT AAT 2784Asn Glu Leu Leu Leu Arg Ile Gly Glu His Tyr Gln Gln Val Phe Asn915 920 925GGT TTG TCA ATA CTT GCC TCA TTT GCA TCC AGT GAT GAT CCA TAT CAG 2832Gly Leu Ser Ile Leu Ala Ser Phe Ala Ser Ser Asp Asp Pro Tyr Gln930 935 940GGC CCG AGA GAT ATC ATA TCA CCT GAA CTG ATG GCT GAT TAT TTA CAA 2880Gly Pro Arg Asp Ile Ile Ser Pro Glu Leu Met Ala Asp Tyr Leu Gln945 950 955 960CCC AAA TTG TTG GGC ATT TTG GCT TTT TTT AAC ATG CAG TTA CTG AGC 2928Pro Lys Leu Leu Gly Ile Leu Ala Phe Phe Asn Met Gln Leu Leu Ser965 970 975TCT AGT GTT GGC ATT GAA GAT AAG AAA ATG GCC TTG AAC AGT TTG ATG 2976Ser Ser Val Gly Ile Glu Asp Lys Lys Met Ala Leu Asn Ser Leu Met980 985 990TCT TTG ATG AAG TTA ATG GGA CCC AAA CAT GTC AGT TCT GTG AGG GTG 3024Ser Leu Met Lys Leu Met Gly Pro Lys His Val Ser Ser Val Arg Val995 10001005AAG ATG ATG ACC ACA CTG AGA ACT GGC CTT CGA TTC AAG GAT GAT TTT 3072Lys Met Met Thr Thr Leu Arg Thr Gly Leu Arg Phe Lys Asp Asp Phe101010151020CCT GAA TTG TGT TGC AGA GCT TGG GAC TGC TTT GTT CGC TGC CTG GAT 3120Pro Glu Leu Cys Cys Arg Ala Trp Asp Cys Phe Val Arg Cys Leu Asp1025103010351040CAT GCT TGT CTG GGC TCC CTT CTC AGT CAT GTA ATA GTA GCT TTG TTA 3168His Ala Cys Leu Gly Ser Leu Leu Ser His Val Ile Val Ala Leu Leu104510501055CCT CTT ATA CAC ATC CAG CCT AAA GAA ACT GCA GCT ATC TTC CAC TAC 3216Pro Leu Ile His Ile Gln Pro Lys Glu Thr Ala Ala Ile Phe His Tyr106010651070CTC ATA ATT GAA AAC AGG GAT GCT GTG CAA GAT TTT CTT CAT GAA ATA 3264Leu Ile Ile Glu Asn Arg Asp Ala Val Gln Asp Phe Leu His Glu Ile107510801085TAT TTT TTA CCT GAT CAT CCA GAA TTA AAA AAG ATA AAA GCC GTT CTC 3312Tyr Phe Leu Pro Asp His Pro Glu Leu Lys Lys Ile Lys Ala Val Leu109010951100CAG GAA TAC AGA AAG GAG ACC TCT GAG AGC ACT GAT CTT CAG ACA ACT 3360Gln Glu Tyr Arg Lys Glu Thr Ser Glu Ser Thr Asp Leu Gln Thr Thr1105111011151120CTT CAG CTC TCT ATG AAG GCC ATT CAA CAT GAA AAT GTC GAT GTT CGT 3408Leu Gln Leu Ser Met Lys Ala Ile Gln His Glu Asn Val Asp Val Arg112511301135ATT CAT GCT CTT ACA AGC TTG AAG GAA ACC TTG TAT AAA AAT CAG GAA 3456Ile His Ala Leu Thr Ser Leu Lys Glu Thr Leu Tyr Lys Asn Gln Glu114011451150AAA CTG ATA AAG TAT GCA ACA GAC AGT GAA ACA GTA GAA CCT ATT ATC 3504Lys Leu Ile Lys Tyr Ala Thr Asp Ser Glu Thr Val Glu Pro Ile Ile115511601165TCA CAG TTG GTG ACA GTG CTT TTG AAA GGT TGC CAA GAT GCA AAC TCT 3552Ser Gln Leu Val Thr Val Leu Leu Lys Gly Cys Gln Asp Ala Asn Ser117011751180CAA GCT CGG TTG CTC TGT GGG GAA TGT TTA GGG GAA TTG GGG GCG ATA 3600Gln Ala Arg Leu Leu Cys Gly Glu Cys Leu Gly Glu Leu Gly Ala Ile1185119011951200GAT CCA GGT CGA TTA GAT TTC TCA ACA ACT GAA ACT CAA GGA AAA GAT 3648Asp Pro Gly Arg Leu Asp Phe Ser Thr Thr Glu Thr Gln Gly Lys Asp120512101215TTT ACA TTT GTG ACT GGA GTA GAA GAT TCA AGC TTT GCC TAT GGA TTA 3696Phe Thr Phe Val Thr Gly Val Glu Asp Ser Ser Phe Ala Tyr Gly Leu122012251230TTG ATG GAG CTA ACA AGA GCT TAC CTT GCG TAT GCT GAT AAT AGC CGA 3744Leu Met Glu Leu Thr Arg Ala Tyr Leu Ala Tyr Ala Asp Asn Ser Arg123512401245GCT CAA GAT TCA GCT GCC TAT GCC ATT CAG GAG TTG CTT TCT ATT TAT 3792Ala Gln Asp Ser Ala Ala Tyr Ala Ile Gln Glu Leu Leu Ser Ile Tyr125012551260GAC TGT AGA GAG ATG GAG ACC AAC GGC CCA GGT CAC CAA TTG TGG AGG 3840Asp Cys Arg Glu Met Glu Thr Asn Gly Pro Gly His Gln Leu Trp Arg1265127012751280AGA TTT CCT GAG CAT GTT CGG GAA ATA CTA GAA CCT CAT CTA AAT ACC 3888Arg Phe Pro Glu His Val Arg Glu Ile Leu Glu Pro His Leu Asn Thr128512901295AGA TAC AAG AGT TCT CAG AAG TCA ACC GAT TGG TCT GGA GTA AAG AAG 3936Arg Tyr Lys Ser Ser Gln Lys Ser Thr Asp Trp Ser Gly Val Lys Lys130013051310CCA ATT TAC TTA AGT AAA TTG GGT AGT AAC TTT GCA GAA TGG TCA GCA 3984Pro Ile Tyr Leu Ser Lys Leu Gly Ser Asn Phe Ala Glu Trp Ser Ala131513201325TCT TGG GCA GGT TAT CTT ATT ACA AAG GTT CGA CAT GAT CTT GCC AGT 4032Ser Trp Ala Gly Tyr Leu Ile Thr Lys Val Arg His Asp Leu Ala Ser133013351340AAA ATT TTC ACC TGC TGT AGC ATT ATG ATG AAG CAT GAT TTC AAA GTG 4080Lys Ile Phe Thr Cys Cys Ser Ile Met Met Lys His Asp Phe Lys Val1345135013551360ACC ATC TAT CTT CTT CCA CAT ATT CTG GTG TAT GTC TTA CTG GGT TGT 4128Thr Ile Tyr Leu Leu Pro His Ile Leu Val Tyr Val Leu Leu Gly Cys136513701375AAT CAA GAA GAT CAG CAG GAG GTT TAT GCA GAA ATT ATG GCA GTT CTA 4176Asn Gln Glu Asp Gln Gln Glu Val Tyr Ala Glu Ile Met Ala Val Leu138013851390AAG CAT GAC GAT CAG CAT ACC ATA AAT ACC CAA GAC ATT GCA TCT GAT 4224Lys His Asp Asp Gln His Thr Ile Asn Thr Gln Asp Ile Ala Ser Asp139514001405CTG TGT CAA CTC AGT ACA CAG ACT GTG TTC TCC ATG CTT GAC CAT CTC 4272Leu Cys Gln Leu Ser Thr Gln Thr Val Phe Ser Met Leu Asp His Leu141014151420ACA CAG TGG GCA AGG CAC AAA TTT CAG GCA CTG AAA GCT GAG AAA TGT 4320Thr Gln Trp Ala Arg His Lys Phe Gln Ala Leu Lys Ala Glu Lys Cys1425143014351440CCA CAC AGC AAA TCA AAC AGA AAT AAG GTA GAC TCA ATG GTA TCT ACT 4368Pro His Ser Lys Ser Asn Arg Asn Lys Val Asp Ser Met Val Ser Thr144514501455GTG GAT TAT GAA GAC TAT CAG AGT GTA ACC CGT TTT CTA GAC CTC ATA 4416Val Asp Tyr Glu Asp Tyr Gln Ser Val Thr Arg Phe Leu Asp Leu Ile146014651470CCC CAG GAT ACT CTG GCA GTA GCT TCC TTT CGC TCC AAA GCA TAC ACA 4464Pro Gln Asp Thr Leu Ala Val Ala Ser Phe Arg Ser Lys Ala Tyr Thr147514801485CGA GCT GTA ATG CAC TTT GAA TCA TTT ATT ACA GAA AAG AAG CAA AAT 4512Arg Ala Val Met His Phe Glu Ser Phe Ile Thr Glu Lys Lys Gln Asn149014951500ATT CAG GAA CAT CTT GGA TTT TTA CAG AAA TTG TAT GCT GCT ATG CAT 4560Ile Gln Glu His Leu Gly Phe Leu Gln Lys Leu Tyr Ala Ala Met His1505151015151520GAA CCT GAT GGA GTG GCC GGA GTC AGT GCA ATT AGA AAG GCA GAA CCA 4609Glu Pro Asp Gly Val Ala Gly Val Ser Ala Ile Arg Lys Ala Glu Pro152515301535TCT CTA AAA GAA CAG ATC CTT GAA CAT GAA AGC CTT GGC TTG CTG AGG 4656Ser Leu Lys Glu Gln Ile Leu Glu His Glu Ser Leu Gly Leu Leu Arg154015451550GAT GCC ACT GCT TGT TAT GAC AGG GCT ATT CAG CTA GAA CCA GAC CAG 4704Asp Ala Thr Ala Cys Tyr Asp Arg Ala Ile Gln Leu Glu Pro Asp Gln155515601565ATC ATT CAT TAC CAT GGT GTA GTA AAG TCC ATG TTA GGT CTT GGT CAG 4752Ile Ile His Tyr His Gly Val Val Lys Ser Met Leu Gly Leu Gly Gln157015751580CTG TCT ACT GTT ATC ACT CAG GTG AAT GGA GTG CAT GCT AAC AGG TCC 4800Leu Ser Thr Val Ile Thr Gln Val Asn Gly Val His Ala Asn Arg Ser1585159015951600GAG TGG ACA GAT GAA TTA AAC ACG TAC AGA GTG GAA GCA GCT TGG AAA 4848Glu Trp Thr Asp Glu Leu Asn Thr Tyr Arg Val Glu Ala Ala Trp Lys160516101615TTG TCA CAG TGG GAT TTG GTG GAA AAC TAT TTG GCA GCA GAT GGA AAA 4896Leu Ser Gln Trp Asp Leu Val Glu Asn Tyr Leu Ala Ala Asp Gly Lys162016251630TCT ACA ACA TGG AGT GTC AGA CTG GGA CAG CTA TTA TTA TCA GCC AAA 4944Ser Thr Thr Trp Ser Val Arg Leu Gly Gln Leu Leu Leu Ser Ala Lys163516401645AAA AGA GAT ATC ACA GCT TTT TAT GAC TCA CTG AAA CTA GTG AGA GCA 4992Lys Arg Asp Ile Thr Ala Phe Tyr Asp Ser Leu Lys Leu Val Arg Ala165016551660GAA CAA ATT GTA CCT CTT TCA GCT GCA AGC TTT GAA AGA GGC TCC TAC 5040Glu Gln Ile Val Pro Leu Ser Ala Ala Ser Phe Glu Arg Gly Ser Tyr1665167016751680CAA CGA GGA TAT GAA TAT ATT GTG AGA TTG CAC ATG TTA TGT GAG TTG 5088Gln Arg Gly Tyr Glu Tyr Ile Val Arg Leu His Met Leu Cys Glu Leu168516901695GAG CAT AGC ATC AAA CCA CTT TTC CAG CAT TCT CCA GGT GAC AGT TCT 5136Glu His Ser Ile Lys Pro Leu Phe Gln His Ser Pro Gly Asp Ser Ser170017051710CAA GAA GAT TCT CTA AAC TGG GTA GCT CGA CTA GAA ATG ACC CAG AAT 5184Gln Glu Asp Ser Leu Asn Trp Val Ala Arg Leu Glu Met Thr Gln Asn171517201725TCC TAC AGA GCC AAG GAG CCT ATC CTG GCT CTC CGG AGG GCT TTA CTA 5232Ser Tyr Arg Ala Lys Glu Pro Ile Leu Ala Leu Arg Arg Ala Leu Leu173017351740AGC CTC AAC AAA AGA CCA GAT TAC AAT GAA ATG GTT GGA GAA TGC TGG 5280Ser Leu Asn Lys Arg Pro Asp Tyr Asn Glu Met Val Gly Glu Cys Trp1745175017551760CTG CAG AGT GCC AGG GTA GCT AGA AAG GCT GGT CAC CAC CAG ACA GCC 5328Leu Gln Ser Ala Arg Val Ala Arg Lys Ala Gly His His Gln Thr Ala176517701775TAC AAT GCT CTC CTT AAT GCA GGG GAA TCA CGA CTC GCT GAA CTG TAC 5376Tyr Asn Ala Leu Leu Asn Ala Gly Glu Ser Arg Leu Ala Glu Leu Tyr178017851790GTG GAA AGG GCA AAG TGG CTC TGG TCC AAG GGT GAT GTT CAC CAG GCA 5424Val Glu Arg Ala Lys Trp Leu Trp Ser Lys Gly Asp Val His Gln Ala179518001805CTA ATT GTT CTT CAA AAA GGT GTT GAA TTA TGT TTT CCT GAA AAT GAA 5472Leu Ile Val Leu Gln Lys Gly Val Glu Leu Cys Phe Pro Glu Asn Glu181018151820ACC CCA CCT GAG GGT AAG AAC ATG TTA ATC CAT GGT CGA GCT ATG CTA 5520Thr Pro Pro Glu Gly Lys Asn Met Leu Ile His Gly Arg Ala Met Leu1825183018351840CTA GTG GGC CGA TTT ATG GAA GAA ACA GCT AAC TTT GAA AGC AAT GCA 5568Leu Val Gly Arg Phe Met Glu Glu Thr Ala Asn Phe Glu Ser Asn Ala184518501855ATT ATG AAA AAA TAT AAG GAT GTG ACC GCG TGC CTG CCA GAA TGG GAG 5616Ile Met Lys Lys Tyr Lys Asp Val Thr Ala Cys Leu Pro Glu Trp Glu186018651870GAT GGG CAT TTT TAC CTT GCC AAG TAC TAT GAC AAA TTG ATG CCC ATG 5664Asp Gly His Phe Tyr Leu Ala Lys Tyr Tyr Asp Lys Leu Met Pro Met187518801885GTC ACA GAC AAC AAA ATG GAA AAG CAA GGT GAT CTC ATC CGG TAT ATA 5712Val Thr Asp Asn Lys Met Glu Lys Gln Gly Asp Leu Ile Arg Tyr Ile189018951900GTT CTT CAT TTT GGC AGA TCT CTA CAA TAT GGA AAT CAG TTC ATA TAT 5760Val Leu His Phe Gly Arg Ser Leu Gln Tyr Gly Asn Gln Phe Ile Tyr1905191019151920CAG TCA ATG CCA CGA ATG TTA ACT CTA TGG CTT GAT TAT GGT ACA AAG 5808Gln Ser Met Pro Arg Met Leu Thr Leu Trp Leu Asp Tyr Gly Thr Lys192519301935GCA TAT GAA TGG GAA AAA GCT GGC CGC TCC GAT CGT GTA CAA ATG AGG 5656Ala Tyr Glu Trp Glu Lys Ala Gly Arg Ser Asp Arg Val Gln Met Arg194019451950AAT GAT TTG GGT AAA ATA AAC AAG GTT ATC ACA GAG CAT ACA AAC TAT 5904Asn Asp Leu Gly Lys Ile Asn Lys Val Ile Thr Glu His Thr Asn Tyr195519601965TTA GCT CCA TAT CAA TTT TTG ACT GCT TTT TCA CAA TTG ATC TCT CGA 5952Leu Ala Pro Tyr Gln Phe Leu Thr Ala Phe Ser Gln Leu Ile Ser Arg197019751980ATT TGT CAT TCT CAC GAT GAA GTT TTT GTT GTC TTG ATG GAA ATA ATA 6000Ile Cys His Ser His Asp Glu Val Phe Val Val Leu Met Glu Ile Ile1985199019952000GCC AAA GTA TTT CTA GCC TAT CCT CAA CAA GCA ATG TGG ATG ATG ACA 6048Ala Lys Val Phe Leu Ala Tyr Pro Gln Gln Ala Met Trp Met Met Thr200520102015GCT GTG TCA AAG TCA TCT TAT CCC ATG CGT GTG AAC AGA TGC AAG GAA 6096Ala Val Ser Lys Ser Ser Tyr Pro Met Arg Val Asn Arg Cys Lys Glu202020252030ATC CTC AAT AAA GCT ATT CAT ATG AAA AAA TCC TTA GAG AAG TTT GTT 6144Ile Leu Asn Lys Ala Ile His Met Lys Lys Ser Leu Glu Lys Phe Val203520402045GGA GAT GCA ACT CGC CTA ACA GAT AAG CTT CTA GAA TTG TGC AAT AAA 6192Gly Asp Ala Thr Arg Leu Thr Asp Lys Leu Leu Glu Leu Cys Asn Lys205020552060CCG GTT GAT GGA AGT AGT TCC ACA TTA AGC ATG AGC ACT CAT TTT AAA 6240Pro Val Asp Gly Ser Ser Ser Thr Leu Ser Met Ser Thr His Phe Lys2065207020752080ATG CTT AAA AAG CTG GTA GAA GAA GCA ACA TTT AGT GAA ATC CTC ATT 6268Met Leu Lys Lys Leu Val Glu Glu Ala Thr Phe Ser Glu Ile Leu Ile208520902095CCT CTA CAA TCA GTC ATG ATA CCT ACA CTT CCA TCA ATT CTG GGT ACC 6336Pro Leu Gln Ser Val Met Ile Pro Thr Leu Pro Ser Ile Leu Gly Thr210021052110CAT GCT AAC CAT GCT AGC CAT GAA CCA TTT CCT GGA CAT TGG GCC TAT 6364His Ala Asn His Ala Ser His Glu Pro Phe Pro Gly His Trp Ala Tyr211521202125ATT GCA GGG TTT GAT GAT ATG GTG GAA ATT CTT GCT TCT CTT CAG AAA 6432Ile Ala Gly Phe Asp Asp Met Val Glu Ile Leu Ala Ser Leu Gln Lys213021352140CCA AAG AAG ATT TCT TTA AAA GGC TCA GAT GGA AAG TTC TAC ATC ATG 6480Pro Lys Lys Ile Ser Leu Lys Gly Ser Asp Gly Lys Phe Tyr Ile Met2145215021552160ATG TGT AAG CCA AAA GAT GAC CTG AGA AAG GAT TGT AGA CTA ATG GAA 6528Met Cys Lys Pro Lys Asp Asp Leu Arg Lys Asp Cys Arg Leu Met Glu216521702175TTC AAT TCC TTG ATT AAT AAG TGC TTA AGA AAA GAT GCA GAG TCT CGT 6576Phe Asn Ser Leu Ile Asn Lys Cys Leu Arg Lys Asp Ala Glu Ser Arg218021852190AGA AGA GAA CTT CAT ATT CGA ACA TAT GCA GTT ATT CCA CTA AAT GAT 6624Arg Arg Glu Leu His Ile Arg Thr Tyr Ala Val Ile Pro Leu Asn Asp219522002205GAA TGT GGG ATT ATT GAA TGG GTG AAC AAC ACT GCT GGT TTG AGA CCT 6672Glu Cys Gly Ile Ile Glu Trp Val Asn Asn Thr Ala Gly Leu Arg Pro221022152220ATT CTG ACC AAA CTA TAT AAA GAA AAG GGA GTG TAT ATG ACA GGA AAA 6720Ile Leu Thr Lys Leu Tyr Lys Glu Lys Gly Val Tyr Met Thr Gly Lys2225223022352240GAA CTT CGC CAG TGT ATG CTA CCA AAG TCA GCA GCT TTA TCT GAA AAA 6768Glu Leu Arg Gln Cys Met Leu Pro Lys Ser Ala Ala Leu Ser Glu Lys224522502255CTC AAA GTA TTC CGA GAA TTT CTC CTG CCC AGG CAT CCT CCT ATT TTT 6816Leu Lys Val Phe Arg Glu Phe Leu Leu Pro Arg His Pro Pro Ile Phe226022652270CAT GAG TGG TTT CTG AGA ACA TTC CCT GAT CCT ACA TCA TGG TAC AGT 6864His Glu Trp Phe Leu Arg Thr Phe Pro Asp Pro Thr Ser Trp Tyr Ser227522802285AGT AGA TCA GCT TAC TGC CGT TCC ACT GCA GTA ATG TCA ATG GTT GGT 6912Ser Arg Ser Ala Tyr Cys Arg Ser Thr Ala Val Met Ser Met Val Gly229022952300TAT ATT CTG GGG CTT GGA GAC CGT CAT GGT GAA AAT ATT CTC TTT GAT 6960Tyr Ile Leu Gly Leu Gly Asp Arg His Gly Glu Asn Ile Leu Phe Asp2305231023152320TCT TTG ACT GGT GAA TGC GTA CAT GTA GAT TTC AAT TGT CTT TTC AAT 7008Ser Leu Thr Gly Glu Cys Val His Val Asp Phe Asn Cys Leu Phe Asn232523302335AAG GGA GAA ACC TTT GAA GTT CCA GAA ATT GTG CCA TTT CGC CTG ACT 7056Lys Gly Glu Thr Phe Glu Val Pro Glu Ile Val Pro Phe Arg Leu Thr234023452350CAT AAT ATG GTT AAT GGA ATG GGT CCT ATG GGA ACA GAG GGT CTT TTT 7104His Asn Met Val Asn Gly Met Gly Pro Met Gly Thr Glu Gly Leu Phe235523602365CGA AGA GCA TGT GAA GTT ACA ATG AGG CTG ATG CTG GAT CAG CGA GAG 7152Arg Arg Ala Cys Glu Val Thr Met Arg Leu Met Arg Asp Gln Arg Glu237023752380CCT TTA ATG AGT GTC TTA AAG ACT TTT CTA CAT GAT CCT CTT GTG GAA 7200Pro Leu Met Ser Val Leu Lys Thr Phe Leu His Asp Pro Leu Val Glu2385239023952400TGG AGT AAA CCA GTG AAA GGG CAT TCC AAA GCG CCA CTG AAT GAA ACT 7148Trp Ser Lys Pro Val Lys Gly His Ser Lys Ala Pro Let Asn Glu Thr240524102415GGA GAA GTT GTC AAT GAA AAG GCC AAG ACC CAT GTT CTT GAC ATT GAG 7196Gly Glu Val Val Asn Glu Lys Ala Lys Thr His Val Leu Asp Ile Glu242024252430CAG CGA CTA CAA GGT GTA ATC AAG ACT CGA AAT AGA GTG ACA GGA CTG 7346Gln Arg Leu Gln Gly Val Ile Lys Thr Arg Asn Arg Val Thr Gly Leu243524402445CCG TTA TCT ATT GAA GGA CAT GTG CAT TAC CTT ATA CAA GAA GCT ACT 7332Pro Leu Ser Ile Glu Gly His Val His Tyr Leu Ile Gln Glu Ala Thr245024552460GAT GAA AAC TTA CTA TGC ACG ATG TAT CTT GGT TGG ACT CCA TAT ATG 7440Asp Glu Asn Leu Leu Cys Gln Met Tyr Leu Gly Trp Thr Pro Tyr Met2465247024752480TGAAATGAAA TTATGTAAAA GAATATGTTA ATAATCTAAA AGTAAAAAAA AAAAAAAAAA7510AA 7512(2)SEQ ID NO33的说明(i)序列特征(A)长度2480个氨基酸(B)类型氨基酸(D)拓扑结构线性(ii)分子类型蛋白(xi)序列描述SEQ ID NO33Met Gly His Ala Val Glu Trp Pro Val Val Met Ser Arg Phe Leu Ser1 5 10 15Gln Leu Asp Glu His Met Gly Tyr Leu Gln Ser Ala Pro Leu Gln Leu20 25 30Met Ser Met Gln Asn Leu Glu Phe Ile Glu Val Thr Leu Leu Met Val35 40 45Leu Thr Arg Ile Ile Ala Ile Val Phe Phe Arg Arg Gln Glu Leu leu50 55 60Leu Trp Gln Ile Gly Cys Val Leu Leu Glu Tyr Gly Ser Pro Lys Ile65 70 75 80Lys Ser Leu Ala Ile Ser Phe Leu Thr Glu Leu Phe Gln Leu Gly Gly85 90 95Leu Pro Ala Gln Pro Ala Ser Thr Phe Phe Ser Ser Phe Leu Glu Leu100 105 110Leu Lys His Leu Val Glu Met Asp Thr Asp Gln Leu Lys Leu Tyr Glu115 120 125Glu Pro Leu Ser Lys Leu Ile Lys Thr Leu Phe Pro Phe Glu Ala Glu130 135 140Ala Tyr Arg Asn Ile Glu Pro Val Tyr Leu Asn Met Leu Leu Glu Lys145 150 155 160Leu Cys Val Met Phe Glu Asp Gly Val Leu Met Arg Leu Lys Ser Asp165 170 175Leu Leu Lys Ala Ala Leu Cys His Leu Leu Gln Tyr Phe Leu Lys Phe180 185 190Val Pro Ala Gly Tyr Glu Ser Ala Leu Gln Val Arg Lys Val Tyr Val195 200 205Arg Asn Ile Cys Lys Ala Leu Leu Asp Val Leu Gly Ile Glu Val Asp210 215 220Ala Glu Tyr Leu Leu Gly Pro Leu Tyr Ala Ala Leu Lys Met Glu Ser225 230 235 240Met Glu Ile Ile Glu Glu Ile Gln Cys Gln Thr Gln Gln Glu Asn Leu245 250 255Ser Ser Asn Ser Asp Gly Ile Ser Pro Lys Arg Arg Arg Leu Ser Ser260 265 270Ser Leu Asn Pro Ser Lys Arg Ala Pro Lys Gln Thr Glu Glu Ile Lys275 280 285His Val Asp Met Asn Gln Lys Ser Ile Leu Trp Ser Ala Leu Lys Gln290 295 300Lys Ala Glu Ser Leu Gln Ile Ser Leu Glu Tyr Ser Gly Leu Lys Asn305 310 315 320Pro Val Ile Glu Met Leu Glu Gly Ile Ala Val Val Leu Gln Leu Thr325 330 335Ala Leu Cys Thr Val His Cys Ser His Gln Asn Met Asn Cys Arg Thr340 345 350Phe Lys Asp Cys Gln His Lys Ser Lys Lys Lys Pro Ser Val Val Ile355 360 365Thr Trp Met Ser Leu Asp Phe Tyr Thr Lys Val Leu Lys Ser Cys Arg370 375 380Ser Leu Leu Glu Ser Val Gln Lys Leu Asp Leu Glu Ala Thr Ile Asp385 390 395 400Lys Val Val Lys Ile Tyr Asp Ala Leu Ile Tyr Met Gln Val Asn Ser405 410 415Ser Phe Glu Asp His Ile Leu Glu Asp Leu Cys Gly Met Leu Ser Leu420 425 430Pro Trp Ile Tyr Ser His Ser Asp Asp Gly Cys Leu Lys Leu Thr Thr435 440 445Phe Ala Ala Asn Leu Leu Thr Leu Ser Cys Arg Ile Ser Asp Ser Tyr450 455 460Ser Pro Gln Ala Gln Ser Arg Cys Val Phe Leu Leu Thr Leu Phe Pro465 470 475 480Arg Arg Ile Phe Leu Glu Trp Arg Thr Ala Val Tyr Asn Trp Ala Leu485 490 495Gln Ser Ser His Glu Val Ile Arg Ala Ser Cys Val Ser Gly Phe Phe500 505 510Ile Leu Leu Gln Gln Gln Asn Ser Cys Asn Arg Val Pro Lys Ile Leu515 520 525Ile Asp Lys Val Lys Asp Asp Ser Asp Ile Val Lys Lys Glu Phe Ala530 535 540Ser Ile Leu Gly Gln Leu Val Cys Thr Leu His Gly Met Phe Tyr Leu545 550 555 560Thr Ser Ser Leu Thr Glu Pro Phe Ser Glu His Gly His Val Asp Leu565 570 575Phe Cys Arg Asn Leu Lys Ala Thr Ser Gln His Glu Cys Ser Ser Ser580 585 590Gln Leu Lys Ala Ser Val Cys Lys Pro Phe Leu Phe Leu Leu Lys Lys595 600 605Lys Ile Pro Ser Pro Val Lys Leu Ala Phe Ile Asp Asn Leu His His610 615 620Leu Cys Lys His Leu Asp Phe Arg Glu Asp Glu Thr Asp Val Lys Ala625 630 635 640Val Leu Gly Thr Leu Leu Asn Leu Met Glu Asp Pro Asp Lys Asp Val645 650 655Arg Val Ala Phe Ser Gly Asn Ile Lys His Ile Leu Glu Ser Leu Asp660 665 670Ser Glu Asp Gly Phe Ile Lys Glu Leu Phe Val Leu Arg Met Lys Glu675 680 685Ala Tyr Thr His Ala Gln Ile Ser Arg Asn Asn Glu Leu Lys Asp Thr690 695 700Leu Ile Leu Thr Thr Gly Asp Ile Gly Arg Ala Ala Lys Gly Asp Leu705 710 715 720Val Pro Phe Ala Leu Leu His Leu Leu His Cys Leu Leu Ser Lys Ser725 730 735Ala Ser Val Ser Gly Ala Ala Tyr Thr Glu Ile Arg Ala Leu Val Ala740 745 750Ala Lys Ser Val Lys Leu Gln Ser Phe Phe Ser Gln Tyr Lys Lys Pro755 760 765Ile Cys Gln Phe Leu Val Glu Ser Leu His Ser Ser Gln Met Thr Ala770 775 780Leu Pro Asn Thr Pro Cys Gln Asn Ala Asp Val Arg Lys Gln Asp Val785 790 795 800Ala His Gln Arg Glu Met Ala Leu Asn Thr Leu Ser Glu Ile Ala Asn805 810 815Val Phe Asp Phe Pro Asp Leu Asn Arg Phe Leu Thr Arg Thr Leu Gln820 825 830Val Leu Leu Pro Asp Leu Ala Ala Lys Ala Ser Pro Ala Ala Ser Ala835 840 845Leu Ile Arg Thr Leu Gly Lys Gln Leu Asn Val Asn Arg Arg Glu Ile850 855 860Leu Ile Asn Asn Phe Lys Tyr Ile Phe Ser His Leu Val Cys Ser Cys865 870 875 880Ser Lys Asp Glu Leu Glu Arg Ala Leu His Tyr Leu Lys Asn Glu Thr885 890 895Glu Ile Glu Leu Gly Ser Leu Leu Arg Glu Asp Phe Gln Gly Leu His900 905 910Asn Glu Leu Leu Leu Arg Ile Gly Glu His Tyr Gln Gln Val Phe Asn915 920 925Gly Leu Ser Ile Leu Ala Ser Phe Ala Ser Ser Asp Asp Pro Tyr Gln930 935 940Gly Pro Arg Asp Ile Ile Ser Pro Glu Leu Met Ala Asp Tyr Leu Gln945 950 955 960Pro Lys Leu Leu Gly Ile Leu Ala Phe Phe Asn Met Gln Leu Leu Ser965 970 975Ser Ser Val Gly Ile Glu Asp Lys Lys Met Ala Leu Asn Ser Leu Met980 985 990Ser Leu Met Lys Leu Met Gly Pro Lys His Val Ser Ser Val Arg Val995 10001005Lys Met Met Thr Thr Leu Arg Thr Gly Leu Arg Phe Lys Asp Asp Phe101010151020Pro Glu Leu Cys Cys Arg Ala Trp Asp Cys Phe Val Arg Cys Leu Asp1025103010351040His Ala Cys Leu Gly Ser Leu Leu Ser His Val Ile Val Ala Leu Leu104510501055Pro Leu Ile His Ile Gln Pro Lys Glu Thr Ala Ala Ile Phe His Tyr106010651070Leu Ile Ile Glu Asn Arg Asp Ala Val Gln Asp Phe Leu His Glu Ile107510801085Tyr Phe Leu Pro Asp His Pro Glu Leu Lys Lys Ile Lys Ala Val Leu109010951100Gln Glu Tyr Arg Lys Glu Thr Ser Glu Ser Thr Asp Leu Gln Thr Thr1105111011151120Leu Gln Leu Ser Met Lys Ala Ile Gln His Glu Asn Val Asp Val Arg112511301135Ile His Ala Leu Thr Ser Leu Lys Glu Thr Leu Tyr Lys Asn Gln Glu114011451150Lys Leu Ile Lys Tyr Ala Thr Asp Ser Glu Thr Val Glu Pro Ile Ile115511601165Ser Gln Leu Val Thr Val Leu Leu Lys Gly Cys Gln Asp Ala Asn Ser117011751180Gln Ala Arg Leu Leu Cys Gly Glu Cys Leu Gly Glu Leu Gly Ala Ile1185119011951200Asp Pro Gly Arg Leu Asp Phe Ser Thr Thr Glu Thr Gln Gly Lys Asp120512101215Phe Thr Phe Val Thr Gly Val Glu Asp Ser Ser Phe Ala Tyr Gly Leu122012251230Leu Met Glu Leu Thr Arg Ala Tyr Leu Ala Tyr Ala Asp Asn Ser Arg123512401245Ala Gln Asp Ser Ala Ala Tyr Ala Ile Gln Glu Leu Leu Ser Ile Tyr125012551260Asp Cys Arg Glu Met Glu Thr Asn Gly Pro Gly His Gln Leu Trp Arg1265127012751280Arg Phe Pro Glu His Val Arg Glu Ile Leu Glu Pro His Leu Asn Thr128512901295Arg Tyr Lys Ser Ser Gln Lys Ser Thr Asp Trp Ser Gly Val Lys Lys130013051310Pro Ile Tyr Leu Ser Lys Leu Gly Ser Asn Phe Ala Glu Trp Ser Ala131513201325Ser Trp Ala Gly Tyr Leu Ile Thr Lys Val Arg His Asp Leu Ala Ser133013351340Lys Ile Phe Thr Cys Cys Ser Ile Met Met Lys His Asp Phe Lys Val1345135013551360Thr Ile Tyr Leu Leu Pro His Ile Leu Val Tyr Val Leu Leu Gly Cys136513701375Asn Gln Glu Asp Gln Gln Glu Val Tyr Ala Glu Ile Met Ala Val Leu138013851390Lys His Asp Asp Gln His Thr Ile Asn Thr Gln Asp Ile Ala Ser Asp139514001405Leu Cys Gln Leu Ser Thr Gln Thr Val Phe Ser Met Leu Asp His Leu141014151420Thr Gln Trp Ala Arg His Lys Phe Gln Ala Leu Lys Ala Glu Lys Cys1425143014351440Pro His Ser Lys Ser Asn Arg Asn Lys Val Asp Ser Met Val Ser Thr144514501455Val Asp Tyr Glu Asp Tyr Gln Ser Val Thr Arg Phe Leu Asp Leu Ile146014651470Pro Gln Asp Thr Leu Ala Val Ala Ser Phe Arg Ser Lys Ala Tyr Thr147514801485Arg Ala Val Met His Phe Glu Ser Phe Ile Thr Glu Lys Lys Gln Asn149014951500Ile Gln Glu His Leu Gly Phe Leu Gln Lys Leu Tyr Ala Ala Met His1505151015151520Glu Pro Asp Gly Val Ala Gly Val Ser Ala Ile Arg Lys Ala Glu Pro152515301535Ser Leu Lys Glu Gln Ile Leu Glu His Glu Ser Leu Gly Leu Leu Arg154015451550Asp Ala Thr Ala Cys Tyr Asp Arg Ala Ile Gln Leu Glu Pro Asp Gln155515601565Ile Ile His Tyr His Gly Val Val Lys Ser Met Leu Gly Leu Gly Glnl57015751580Leu Ser Thr Val Ile Thr Gln Val Asn Gly Val His Ala Asn Arg ser1585159015951600Glu Trp Thr Asp Glu Leu Asn Thr Tyr Arg Val Glu Ala Ala Trp Lys160516101615Leu Ser Gln Trp Asp Leu Val Glu Asn Tyr Leu Ala Ala Asp Gly Lys162016251630Ser Thr Thr Trp Ser Val Arg Leu Gly Gln Leu Leu Leu Ser Ala Lys163516401645Lys Arg Asp Ile Thr Ala Phe Tyr Asp Ser Leu Lys Leu Val Arg Ala165016551660Glu Gln Ile Val Pro Leu Ser Ala Ala Ser Phe Glu Arg Gly Ser Tyr1665167016751680Gln Arg Gly Tyr Glu Tyr Ile Val Arg Leu His Met Leu Cys Glu Leu168516901695Glu His Ser Ile Lys Pro Leu Phe Gln His Ser Pro Gly Asp Ser Ser170017051710Gln Glu Asp Ser Leu Asn Trp Val Ala Arg Leu Glu Met Thr Gln Asn171517201725Ser Tyr Arg Ala Lys Glu Pro Ile Leu Ala Leu Arg Arg Ala Leu Leu173017351740Ser Leu Asn Lys Arg Pro Asp Tyr Asn Glu Met Val Gly Glu Cys Trp1745175017551760Leu Gln Ser Ala Arg Val Ala Arg Lys Ala Gly His His Gln Thr Ala176517701775Tyr Asn Ala Leu Leu Asn Ala Gly Glu Ser Arg Leu Ala Glu Leu Tyr178017851790Val Glu Arg Ala Lys Trp Leu Trp Ser Lys Gly Asp Val His Gln Ala179518001805Leu Ile Val Leu Gln Lys Gly Val Glu Leu Cys Phe Pro Glu Asn Glu181018151820Thr Pro Pro Glu Gly Lys Asn Met Leu Ile His Gly Arg Ala Met Leu1825183018351840Leu Val Gly Arg Phe Met Glu Glu Thr Ala Asn Phe Glu Ser Asn Ala184518501855Ile Met Lys Lys Tyr Lys Asp Val Thr Ala Cys Leu Pro Glu Trp Glu186018651870Asp Gly His Phe Tyr Leu Ala Lys Tyr Tyr Asp Lys Leu Met Pro Met187518801885Val Thr Asp Asn Lys Met Glu Lys Gln Gly Asp Leu Ile Arg Tyr Ile189018951900Val Leu His Phe Gly Arg Ser Leu Gln Tyr Gly Asn Gln Phe Ile Tyr1905191019151920Gln Ser Met Pro Arg Met Leu Thr Leu Trp Leu Asp Tyr Gly Thr Lys192519301935Ala Tyr Glu Trp Glu Lys Ala Gly Arg Ser Asp Arg Val Gln Met Arg194019451950Asn Asp Leu Gly Lys Ile Asn Lys Val Ile Thr Glu His Thr Asn Tyr195519601965Leu Ala Pro Tyr Gln Phe Leu Thr Ala Phe Ser Gln Leu Ile Ser Arg197019751980Ile Cys His Ser His Asp Glu Val Phe Val Val Leu Met Glu Ile Ile1985199019952000Ala Lys Val Phe Leu Ala Tyr Pro Gln Gln Ala Met Trp Met Met Thr200520102015Ala Val Ser Lys Ser Ser Tyr Pro Met Arg Val Asn Arg Cys Lys Glu202020252030Ile Leu Asn Lys Ala Ile His Met Lys Lys Ser Leu Glu Lys Phe Val203520402045Gly Asp Ala Thr Arg Leu Thr Asp Lys Let Leu Glu Leu Cys Asn Lys205020552060Pro Val Asp Gly Ser Ser Ser Thr Leu Ser Met Ser Thr His Phe Lys2065207020752080Met Leu Lys Lys Leu Val Glu Glu Ala Thr Phe Ser Glu Ile Leu Ile208520902095Pro Leu Gln Ser Val Met Ile Pro Thr Leu Pro Ser Ile Leu Gly Thr210021052110His Ala Asn His Ala Ser His Glu Pro Phe Pro Gly His Trp Ala Tyr211521202125Ile Ala Gly Phe Asp Asp Met Val Glu Ile Leu Ala Ser Leu Gln Lys213021352140Pro Lys Lys Ile Ser Leu Lys Gly Ser Asp Gly Lys Phe Tyr Ile Met2145215021552160Met Cys Lys Pro Lys Asp Asp Leu Arg Lys Asp Cys Arg Leu Met Glu216521702175Phe Asn Ser Leu Ile Asn Lys Cys Leu Arg Lys Asp Ala Glu Ser Arg218021852190Arg Arg Glu Leu His Ile Arg Thr Tyr Ala Val Ile Pro Leu Asn Asp219522002205Glu Cys Gly Ile Ile Glu Trp Val Asn Asn Thr Ala Gly Leu Arg Pro221022152220Ile Leu Thr Lys Leu Tyr Lys Glu Lys Gly Val Tyr Met Thr Gly Lys2225223022352240Glu Leu Arg Gln Cys Met Leu Pro Lys Ser Ala Ala Leu Ser Glu Lys224522502255Leu Lys Val Phe Arg Glu Phe Leu Leu Pro Arg His Pro Pro Ile Phe226022652270His Glu Trp Phe Leu Arg Thr Phe Pro Asp Pro Thr Ser Trp Tyr Ser227522802285Ser Arg Ser Ala Tyr Cys Arg Ser Thr Ala Val Met Ser Met Val Gly229022952300Tyr Ile Leu Gly Leu Gly Asp Arg His Gly Glu Asn Ile Leu Phe Asp2305231023152320Ser Leu Thr Gly Glu Cys Val His Val Asp Phe Asn Cys Leu Phe Asn232523302335Lys Gly Glu Thr Phe Glu Val Pro Glu Ile Val Pro Phe Arg Leu Thr234023452350His Asn Met Val Asn Gly Met Gly Pro Met Gly Thr Glu Gly Leu Phe235523602365Arg Arg Ala Cys Glu Val Thr Met Arg Leu Met Arg Asp Gln Arg Glu237023752380Pro Leu Met Ser Val Leu Lys Thr Phe Leu His Asp Pro Leu Val Glu2385239023952400Trp Ser Lys Pro Val Lys Gly His Ser Lys Ala Pro Leu Asn Glu Thr240524102415Gly Glu Val Val Asn Glu Lys Ala Lys Thr His Val Leu Asp Ile Glu242024252430Gln Arg Leu Gln Gly Val Ile Lys Thr Arg Asn Arg Val Thr Gly Leu243524402445Pro Leu Ser Ile Glu Gly His Val His Tyr Leu Ile Gln Glu Ala Thr245024552460Asp Glu Asn Leu Leu Cys Gln Met Tyr Leu Gly Trp Thr Pro Tyr Met2465247024752480(2)SEQ ID NO34的说明(i)序列特征(A)长度9385个碱基对(B)类型核苷酸(C)链型单链(D)拓扑结构线性(ii)分子类型cDNA(ix)特征(A)姓名/符号CDS(B)位置190..9357(xi)序列描述SEQ ID NO34GCGAGAGGAG TCGGGATCTG CGCTGCAGCC ACCGCCGCGG TTGATACTAC TTTGACCTTC60CGAGTGCAGT GAGGCATACA TCACAATTTG GAATTATGCA TTGGTTTATC AATTTACTTG120TTTATTGTCA CCCTGCTGCC CAGATATGAC TTCATGAGGA CAGTGATGTG TGTTCTGAAA180TTGTGAACC ATG AGT CTA GTA CTT AAT GAT CTG CTT ATC TGC TGC CGT228Met Ser Leu Val Leu Asn Asp Leu Leu Ile Cys Cys Arg1 5 10CAA CTA GAA CAT GAT AGA GCT ACA GAA CGA AAG AAA GAA GTT GAG AAA 276Gln Leu Glu His Asp Arg Ala Thr Glu Arg Lys Lys Glu Val Glu Lys15 20 25TTT AAG CGC CTG ATT CGA GAT CCT GAA ACA ATT AAA CAT CTA GAT CGG 324Phe Lys Arg Leu Ile Arg Asp Pro Glu Thr Ile Lys His Leu Asp Arg30 35 40 45CAT TCA GAT TCC AAA CAA GGA AAA TAT TTG AAT TGG GAT GCT GTT TTT 372His Ser Asp Ser Lys Gln Gly Lys Tyr Leu Asn Trp Asp Ala Val Phe50 55 60AGA TTT TTA CAG AAA TAT ATT CAG AAA GAA ACA GAA TGT CTG AGA ATA 420Arg Phe Leu Gln Lys Tyr Ile Gln Lys Glu Thr Glu Cys Leu Arg Ile65 70 75GCA AAA CCA AAT GTA TCA GCC TCA ACA CAA GCC TCC AGG CAG AAA AAG 468Ala Lys Pro Asn Val Ser Ala Ser Thr Gln Ala Ser Arg Gln Lys Lys80 85 90ATG CAG GAA ATC AGT AGT TTG GTC AAA TAC TTC ATC AAA TGT GCA AAC 516Met Gln Glu Ile Ser Ser Leu Val Lys Tyr Phe Ile Lys Cys Ala Asn95 100 105AGA AGA GCA CCT AGG CTA AAA TGT CAA GAA CTC TTA AAT TAT ATC ATG 564Arg Arg Ala Pro Arg Leu Lys Cys Gln Glu Leu Leu Asn Tyr Ile Met110 115 120 125GAT ACA GTG AAA GAT TCA TCT AAT GGT GCT ATT TAC GGA GCT GAT TGT 612Asp Thr Val Lys Asp Ser Ser Asn Gly Ala Ile Tyr Gly Ala Asp Cys130 135 140AGC AAC ATA CTA CTC AAA GAC ATT CTT TCT GTG AGA AAA TAC TGG TGT 660Ser Asn Ile Leu Leu Lys Asp Ile Leu Ser Val Arg Lys Tyr Trp Cys145 150 155GAA ATA TCT CAG CAA CAG TGG TTA GAA TTG TTC TCT GTG TAC TTC AGG 708Glu Ile Ser Gln Gln Gln Trp Leu Glu Leu Phe Ser Val Tyr Phe Arg160 165 170CTC TAT CTG AAA CCT TCA CAA GAT GTT CAT AGA GTT TTA GTG GCT AGA 756Leu Tyr Leu Lys Pro Ser Gln Asp Val His Arg Val Leu Val Ala Arg175 180 185ATA ATT CAT GCT GTT ACC AAA GGA TGC TGT TCT CAG ACT GAC GGA TTA 804Ile Ile His Ala Val Thr Lys Gly Cys Cys Ser Gln Thr Asp Gly Leu190 195 200 205AAT TCC AAA TTT TTG GAC TTT TTT TCC AAG GCT ATT CAG TGT GCG AGA 852Asn Ser Lys Phe Leu Asp Phe Phe Ser Lys Ala Ile Gln Cys Ala Arg210 215 220CAA GAA AAG AGC TCT TCA GGT CTA AAT CAT ATC TTA GCA GCT CTT ACT 900Gln Glu Lys Ser Ser Ser Gly Leu Asn His Ile Leu Ala Ala Leu Thr225 230 235ATC TTC CTC AAG ACT TTG GCT GTC AAC TTT CGA ATT CGA GTG TGT GAA 948Ile Phe Leu Lys Thr Leu Ala Val Asn Phe Arg Ile Arg Val Cys Glu240 245 250TTA GGA GAT GAA ATT CTT CCC ACT TTG CTT TAT ATT TGG ACT CAA CAT 996Leu Gly Asp Glu Ile Leu Pro Thr Leu Leu Tyr Ile Trp Thr Gln His255 260 265AGG CTT AAT GAT TCT TTA AAA GAA GTC ATT ATT GAA TTA TTT CAA CTG 1044Arg Leu Asn Asp Ser Leu Lys Glu Val Ile Ile Glu Leu Phe Gln Leu270 275 280 285CAA ATT TAT ATC CAT CAT CCG AAA GGA GCC AAA ACC CAA GAA AAA GGT 1092Gln Ile Tyr Ile His His Pro Lys Gly Ala Lys Thr Gln Glu Lys Gly290 295 300GCT TAT GAA TCA ACA AAA TGG AGA AGT ATT TTA TAC AAC TTA TAT GGT 1140Ala Tyr Glu Ser Thr Lys Trp Arg Ser Ile Leu Tyr Ast Leu Tyr Asp305 310 315CTG CTA GTG AAT GAG ATA AGT CAT ATA GGA AGT AGA GGA AAG TAT TCT 1168Leu Leu Val Asn Glu Ile Ser His Ile Gly Ser Arg Gly Lys Tyr Ser320 325 330TCA GGA TTT CGT AAT ATT GCC GTC AAA GAA AAT TTG ATT GAA TTG ATG 1236Ser Gly Phe Arg Asn Ile Ala Val Lys Glu Asn Leu Ile Glu Leu Met335 340 345GCA GAT ATC TGT CAC CAG GTT TTT AAT GAA GAT ACC AGA TCC TTG GAG 1254Ala Asp Ile Cys His Gln Val Phe Asp Glu Asp Thr Arg Ser Leu Glu350 355 360 365ATT TCT CAA TCT TAC ACT ACT ACA CAA AGA GAA TCT AGT GAT TAC AGT 1332Ile Ser Gln Ser Tyr Thr Thr Thr Gln Arg Glu Ser Ser Asp Tyr Ser370 375 380GTC CCT TGC AAA AGG AAG AAA ATA GAA CTA GGC TGG GAA GTA ATA AAA 1360Val Pro Cys Lys Arg Lys Lys Ile Glu Leu Gly Trp Glu Val Ile Lys385 390 395GAT CAC CTT CAG AAG TCA CAG AAT GAT TTT GAT CTT GTG CCT TGG CCA 1423Asp His Leu Gln Lys Ser Gln Asn Asp Phe Asp Leu Val Pro Trp Leu400 405 410CAG ATT GCA ACC CAA TTA ATA TCA AAG TAT CCT GCA AGT TTA CCT AAC 1475Gln Ile Ala Thr Gln Leu Ile Ser Lys Tyr Pro Ala Ser Leu Pro Asn415 420 425TGT GAG CTG TCT CCA TTA CTG ATG ATA CTA TCT CAG CTT CTA CCC CAA 1524Cys Glu Leu Ser Pro Leu Leu Met Ile Leu Ser Gln Leu Leu Pro Gln430 435 440 445CAG CGA CAT GGG GAA CGT ACA CCA TAT GTG TTA GGA TGC CTT ACG GAA 1572Gln Arg His Gly Glu Arg Thr Pro Tyr Val Leu Arg Cys Leu Thr Glu450 455 460GTT GCA TTG TGT CAA GAC AAG AGG TCA AAC CTA GAA AGC TCA CAA AAG 1622Val Ala Leu Cys Gln Asp Lys Arg Ser Asn Leu Glu Ser Ser Gln Lys465 470 475TCA GAT TTA TTA AAA CTC TGG AAT AAA ATT TGG TGT ATT ACC TTT CGT 1663Ser Asp Leu Leu Lys Leu Trp Asn Lys Ile Trp Cys Ile Thr Phe Arg480 485 490GGT ATA AGT TCT GAG CAA ATA CAA GCT GAA AAC TTT GGC TTA CTT GGA 1716Gly Ile Ser Ser Glu Gln Ile Gln Ala Glu Asn Phe Gly Leu Leu Gly495 500 505GCC ATA ATT CAG GGT AGT TTA GTT GAG GTT GAC AGA GAA TTC TGG AAG 1764Ala Ile Ile Gln Gly Ser Leu Val Glu Val Asp Arg Glu Phe Trp Lys510 515 520 525TTA TTT ACT GGG TCA GCC TGC AGA CCT TCA TGT CCT GCA GTA TGC TGT 1812Leu Phe Thr Gly Ser Ala Cys Arg Pro Ser Cys Pro Ala Val Cys Cys530 535 540TTG ACT TTG GCA CTG ACC ACC AGT ATA GTT CCA GGA GCG GTA AAA ATG 1860Leu Thr Leu Ala Leu Thr Thr Ser Ile Val Pro Gly Ala Val Lys Met545 550 555GGA ATA GAG CAA AAT ATG TGT GAA GTA AAT AGA AGC TTT TCT TTA AAG 1908Gly Ile Glu Gln Asn Met Cys Glu Val Asr Arg Ser Phe Ser Leu Lys560 565 570GAA TCA ATA ATG AAA TGG CTC TTA TTC TAT CAG TTA GAG GGT GAC TTA 1956Glu Ser Ile Met Lys Trp Leu Leu Phe Tyr Gln Leu Glu Gly Asp Leu575 580 585GAA AAT AGC ACA GAA GTG CCT CCA ATT CTT CAC AGT AAT TTT CCT CAT 2004Glu Asn Ser Thr Glu Val Pro Pro Ile Leu His Ser Asn Phe Pro His590 595 600 605CTT GTA CTG GAG AAA ATT CTT GTG AGT CTC ACT ATG AAA AAC GTT AAA 2052Leu Val Leu Glu Lys Ile Leu Val Ser Leu Thr Met Lys Asn Cys Lys610 615 620GCT GCA ATG AAT TTT TTC CAA AGC GTG CCA GAA TGT GAA CAC CAC CAA 2123Ala Ala Met Asn Phe Phe Gln Ser Val Pro Glu Cys Glu His His Gln625 630 635AAA GAT AAA GAA GAA CTT TCA GTC TCA GAA GTA GAA GAA CTA TTT CTT 2143Lys Asp Lys Glu Glu Leu Ser Phe Ser Glu Val Glu Glu Leu The Leu640 645 650CAG ACA ACT TTT GAC AAG ATG GAC TTT TTA ACC ATT GTG AGA GAA TGT 2196Gln Thr Thr Phe Asp Lys Met Asp Phe Leu Thr Ile Val Arg Glu Cys655 660 665GGT ATA GAA AAG CAC CAG TCC AGT ATT GGC TTC TCT GTC CAC CAG AAT 2244Gly Ile Glu Lys His Gln Ser Ser Ile Gly Phe Ser Val His Gln Asn670 675 680 685CTC AAG GAA TCA CTG GAT CGC TGT CTT CTG GGA TTA TCA GAA CAG CTT 2292Leu Lys Glu Ser Leu Asp Arg Cys Leu Leu Gly Leu Ser Glu Gln Leu690 695 700CTG AAT AAT TAC TCA TCT GAG ATT ACA AAT TCA GAA ACT TTT GTC CGG 2343Leu Asn Asn Tyr Ser Ser Glu Ile Thr Asn Ser Glu Thr Leu Val Arg705 710 715TGT TCA CGT CTT TTG GTG GGT GTC CTT GGC GGC TGC TGT TAC ATG GGT 2353Cys Ser Arg Leu Leu Val Gly Val Leu Gly Cys Tyr Cys Tyr Met Gly720 725 730GTA ATA GCT GAA GAG GAA GCA TAT AAG TCA GAA TTA TTC CAG AAA GCT 2436Val Ile Ala Glu Glu Glu Ala Tyr Lys Ser Glu Leu Phe Gln Lys Ala735 740 754AAC TCT CTA ATG CAA TGT GCA GGA GAA AGT ATC ACT CTG TTT AAA AAC 2454Asn Ser Leu Met Gln Cys Ala Gly Glu Ser Ile Thr Leu Phe Lys Asn750 755 760 765AAG ACA AAT GAG GAA TTC AGA ATT GGT TCC TTG AGA AAT ATG ATG CAG 2533Lys Thr Asn Glu Glu Phe Arg Ile Gly Ser Leu Arg Asn Met Met Gln770 775 750CTA TGT ACA CGT TGC TTG AGC AAC TGT ACC AAG AAG AGT CCA AAT AAG 2581Leu Cys Thr Arg Cys Leu Ser Asn Cys Thr Lys Lys Ser Pro Asn Lys785 790 795ATT GCA TCT GGC TTT TTC CTG CGA TTG TTA ACA TCA AAG CTA ATG AAT 2623Ile Ala Ser Gly Phe Phe Leu Arg Leu Leu Thr Ser Lys Leu Met Asn800 805 810GAC ATT GCA GAT ATT TGT AAA AGT TTA GCA TCC TTC ATC AAA AAG CCA 2676Asp Ile Ala Asp Ile Cys Lys Ser Leu Ala Ser Phe Ile Lys Lys Pro815 820 825TTT GAC CGT GGA GAA GTA GAA TCA ATG GAA GAT GAT ACT AAT GGA AAT 2724Phe Asp Arg Gly GLu Val Glu Ser Met Glu Asp Asp Thr Asn Gly Asn830 835 840 845CTA ATG GAG GTG GAG GAT CAG TCA TCC ATG AAT CTA TTT AAC GAT TAC 2772Leu Met Glu Val Glu Asp Gln Ser Ser Met Asn Leu Phe Asn Asp Tyr850 855 860CCT GAT AGT AGT GTT AGT GAT GCA AAC GAA CCT GGA GAG AGC CAA AGT 2820Pro Asp Ser Ser Val Ser Asp Ala Asn Glu Pro Gly Glu Ser Gln Ser865 870 875ACC ATA GGT GCC ATT AAT CCT TTA GCT GAA GAA TAT CTG TCA AAG CAA 2868Thr Ile Gly Ala Ile Asn Pro Leu Ala Glu Glu Tyr Leu Ser Lys Gln880 885 890GAT CTA CTT TTC TTA GAC ATG CTC AAG TTC TTG TGT TTG TGT GTA ACT 2916Asp Leu Leu Phe Leu Asp Met Leu Lys Phe Leu Cys Leu Cys Val Thr895 900 905ACT GCT CAG ACC AAT ACT GTG TCC TTT AGG GCA GCT GAT ATT CGG AGG 2964Thr Ala Gln Thr Asn Thr Val Ser Phe Arg Ala Ala Asp Ile Arg Arg910 915 920 925AAA TTG TTA ATG TTA ATT GAT TCT AGC ACG CTA GAA CCT ACC AAA TCC 3012Lys Leu Leu Met Leu Ile Asp Ser Ser Thr Leu Glu Pro Thr Lys Ser930 935 940CTC CAC CTG CAT ATG TAT CTA ATG CTT TTA AAG GAG CTT CCT GGA GAA 3060Leu His Leu His Met Tyr Leu Met Leu Leu Lys Glu Leu Pro Gly Glu945 950 955GAG TAC CCC TTG CCA ATG GAA GAT GTT CTT GAA CTT CTG AAA CCA CTA 3108Glu Tyr Pro Leu Pro Met Glu Asp Val Leu Glu Leu Leu Lys Pro Leu960 965 970TCC AAT GTG TGT TCT TTG TAT CGT CGT GAC CAA GAT GTT TGT AAA ACT 3156Ser Asn Val Cys Ser Leu Tyr Arg Arg Asp Gln Asp Val Cys Lys Thr975 980 985ATT TTA AAC CAT GTC CTT CAT GTA GTG AAA AAC CTA GGT CAA AGC AAT 3204Ile Leu Asn His Val Leu His Val Val Lys Asn Leu Gly Gln Ser Asn990 995 10001005ATG GAC TCT GAG AAC ACA AGG GAT GCT CAA GGA CAG TTT CTT ACA GTA 3252Met Asp Ser Glu Asn Thr Arg Asp Ala Gln Gly Gln Phe Leu Thr Val101010151020ATT GGA GCA TTT TGG CAT CTA ACA AAG GAG AGG AAA TAT ATA TTC TCT 3300Ile Gly Ala Phe Trp His Leu Thr Lys Glu Arg Lys Tyr Ile Phe Ser102510301035GTA AGA ATG GCC CTA GTA AAT TGC CTT AAA ACT TTG CTT GAG GCT GAT 3348Val Arg Met Ala Leu Val Asn Cys Leu Lys Thr Leu Leu Glu Ala Asp104010451050CCT TAT TCA AAA TGG GCC ATT CTT AAT GTA ATG GGA AAA GAC TTT CCT 3396Pro Tyr Ser Lys Trp Ala Ile Leu Asn Val Met Gly Lys Asp Phe Pro105510601065GTA AAT GAA GTA TTT ACA CAA TTT CTT GCT GAC AAT CAT CAC CAA GTT 3444Val Asn Glu Val Phe Thr Gln Phe Leu Ala Asp Asn His His Gln Val1070107510801085CGC ATG TTG GCT GCA GAG TCA ATC AAT AGA TTG TTC CAG GAC ACG AAG 3492Arg Met Leu Ala Ala Glu Ser Ile Asn Arg Leu Phe Gln Asp Thr Lys109010951100GGA GAT TCT TCC AGG TTA CTG AAA GCA CTT CCT TTG AAG CTT CAG CAA 3540Gly Asp Ser Ser Arg Leu Leu Lys Ala Leu Pro Leu Lys Leu Gln Gln110511101115ACA GCT TTT GAA AAT GCA TAC TTG AAA GCT CAG GAA GGA ATG AGA GAA 3555Thr Ala Phe Glu Asn Ala Tyr Leu Lys Ala Gln Glu Gly Met Arg Glu112011251130ATG TCC CAT AGT GCT GAG AAC CCT GAA ACT TTG GAT GAA ATT TAT AAT 3636Met Ser His Ser Ala Glu Asn Pro Glu Thr Leu Asp Glu Ile Tyr Asn113511401145AGA AAA TCT GTT TTA CTG ACG TTG ATA GCT GTG GTT TTA TCC TGT AGC 3654Arg Lys Ser Val Leu Thu Thr Leu Ile Ala Val Val Leu Ser Cys Ser1150115511601165CCT ATC TGC GAA AAA CAG GCT TTG TTT GCC CTG TGT AAA TCT GTG AAA 3732Pro Ile Cys Glu Lys Gln Ala Leu Phe Ala Leu Cys Lys Ser Val Lys117011751180GAG AAT GGA TTA GAA CCT CAC CTT GTG AAA AAG GTT TTA GAG AAA GTT 3750Glu Asn Gly Leu Glu Pro His Leu Val Lys Lys Val Leu Glu Lys Val118511901195TCT GAA ACT TTT GGA TAT AGA CGT TTA GAA GAC TTT ATG GCA TCT CAT 3828Ser Glu Thr Phe Gly Tyr Arg Arg Leu Glu Asp Phe Met Ala Ser His120012051210TTA GAT TAT CTG GTT TTG GAA TGG CTA AAT CTT CAA GAT ACT GAA TAC 3876Leu Asp Tyr Leu Val Leu Glu Trp Leu Asn Leu Gln Asp Thr Glu Tyr121512201225AAC TTA TCT TCT TTT CCT TTT ATT TTA TTA AAC TAC ACA AAT ATT GAG 3924Asn Leu Ser Ser Phe Pro Phe Ile Leu Leu Asn Tyr Thr Asn Ile Glu1230123512401245GAT TTC TAT AGA TCT TGT TAT AAG GTT TTG ATT CCA CAT CTG GTG ATT 3972Asp Phe Tyr Arg Ser Cys Tyr Lys Val Leu Ile Pro His Leu Val Ile125012551260AGA AGT CAT TTT GAT GAG GTG AAG TCC ATT GTT AAT CAG ATT CAA GAG 4022Arg Ser His Phe Asp Glu Val Lys Ser Ile Ala Asn Gln Ile Gln Glu126512701275GAC TGG AAA AGT CTT CTA ACA GAC TGC TTT CCA AAG ATT CTT GTA AAT 4063Asp Trp Lys Ser Leu Leu Thr Asp Cys Phe Pro Lys Ile Leu Val Asn128012851290ATT CTT CCT TAT TTT GCC TAT GAG GGT ACC AGA GAC AGT GGG ATG GCA 4116Ile Leu Pro Tyr Phe Ala Tyr Glu Gly Thr Arg Asp Ser Gly Met Ala129513001305CAG CAA AGA GAG ACT GCT ACC AAG GTC TAT GAT ATG CTT AAA AGT GAA 4164Gln Gln Arg Glu Ahr Ala Thr Lys Val Tyr Asp Met Leu Lys Ser Glu1310131513201325AAC TTA TTG GGA AAA CAG ATT GAT CAC TTA TTC ATT AGT AAT TTA CCA 4211Asn Leu Leu Gly Lys Gln Ile Asp His Leu Phe Ile Ser Asn Leu Pro133013351340GAG ATT GTG GTG GAG TTA TTG ATG ACG TTA CAT GAG CCA GCA AAT TCT 4260Glu Ile Val Val Glu Leu Leu Met Thr Leu His Glu Pro Ala Asp Ser134513501355AGT GCC AGT CAG AGC ACT GAC CTC TGT GAC TTT TCA GGG GAT TTG GAT 4308Ser Ala Ser Gln Ser Thr Asp Leu Cys Asp Phe Ser Gly Asp Leu Asp136013651370CCT GCT CCT AAT CCA CCT CAT TTT CCA TCG CAT GTG ATT AAA GCA ACA 4356Pro Ala Pro Asn Pro Pro His Phe Pro Ser His Val Ile Lys Ala Thr137513801385TTT GCC TAT ATC AGC AAT TGT CAT AAA ACC AAG TTA AAA AGC ATT TTA 4404Phe Ala Tyr Ile Ser Asn Cys His Lys Thr Lys Leu Lys Ser Ile Leu1390139514001405GAA ATT CTT TCC AAA AGC CCT GAT TCC TAT CAG AAA ATT CTT CTT GCC 4452Glu Ile Leu Ser Lys Ser Pro Asp Ser Tyr Gln Lys Ile Leu Leu Ala141014151420ATA TGT GAG CAA GCA GCT GAA ACA AAT AAT GTT TAT AAG AAG CAC AGA 4500Ile Cys Glu Gln Ala Ala Glu Thr Asn Asn Val Tyr Lys Lys His Arg142514301435ATT CTT AAA ATA TAT CAC CTG TTT GTT AGT TTA TTA CTG AAA GAT ATA 4548Ile Leu Lys Ile Tyr His Leu Phe Val Ser Leu Leu Leu Lys Asp Ile144014451450AAA AGT GGC TTA GGA GGA GCT TGG GCC TTT GTT CTT CGA GAC GTT ATT 4596Lys Ser Gly Leu Gly Gly Ala Trp Ala Phe Val Leu Arg Asp Val Ile145514601465TAT ACT TTG ATT CAC TAT ATC AAC CAA AGG CCT TCT TGT ATC ATG GAT 4644Tyr Thr Leu Ile His Tyr Ile Asn Gln Arg Pro Ser Cys Ile Met Asp1470147514801485GTG TCA TTA CGT AGC TTC TCC CTT TGT TGT GAC TTA TTA AGT CAG GTT 4692Val Ser Leu Arg Ser Phe Ser Leu Cys Cys Asp Leu Leu Ser Gln Val149014951500TGC CAG ACA GCC GTG ACT TAC TGT AAG GAT GCT CTA GAA AAC CAT CTT 4740Cys Gln Thr Ala Val Thr Tyr Cys Lys Asp Ala Leu Glu Asn His Leu150515101515CAT GTT ATT GTT GGT ACA CTT ATA CCC CTT GTG TAT GAG CAG GTG GAG 4788His Val Ile Val Gly Thr Leu Ile Pro Leu Val Tyr Glu Gln Val Glu152015251530GTT CAG AAA CAG GTA TTG GAC TTG TTG AAA TAC TTA GTG ATA GAT AAC 4836Val Gln Lys Gln Val Leu Asp Leu Leu Lys Tyr Leu Val Ile Asp Asn153515401545AAG GAT AAT GAA AAC CTC TAT ATC ACG ATT AAG CTT TTA GAT CCT TTT 4884Lys Asp Asn Glu Asn Leu Tyr Ile Thr Ile Lys Leu Leu Asp Pro Phe1550155515601565CCT GAC CAT GTT GTT TTT AAG GAT TTG CGT ATT ACT CAG CAA AAA ATC 4932Pro Asp His Val Val Phe Lys Asp Leu Arg Ile Thr Gln Gln Lys Ile157015751580AAA TAC AGT AGA GGA CCC TTT TCA CTC TTG GAG GAA ATT AAC CAT TTT 4980Lys Tyr Ser Arg Gly Pro Phe Ser Leu Leu Glu Glu Ile Asn His Phe158515901595CTC TCA GTA AGT GTT TAT GAT GCA CTT CCA TTG ACA AGA CTT GAA GGA 5026Leu Ser Val Ser Val Tyr Asp Ala Leu Pro Leu Thr Arg Leu Glu Gly160016051610CTA AAG GAT CTT CGA AGA CAA CTG GAA CTA CAT AAA GAT CAG ATG GTG 5076Leu Lys Asp Leu Arg Arg Gln Leu Glu Leu His Lys Asp Gln Met Val161516201625GAC ATT ATG AGA GCT TCT CAG GAT AAT CCG CAA GAT GGG ATT ATG GTG 5124Asp Ile Met Arg Ala Ser Gln Asp Asn Pro Gln Asp Gly Ile Met Val1630163516401645AAA CTA GTT GTC AAT TTG TTG CAG TTA TCC AAG ATG GCA ATA AAC CAC 5172Lys Leu Val Val Asn Leu Leu Gln Leu Ser Lys Met Ala Ile Asn His165016551660ACT GGT GAA AAA GAA GTT CTA GAG GCT GTT GGA AGC TGC TTG GGA GAA 5220Thr Gly Glu Lys Glu Val Leu Glu Ala Val Gly Ser Cys Leu Gly Glu166516701675GTG GGT CCT ATA GAT TTC TCT ACC ATA GCT ATA CAA CAT AGT AAA GAT 5268Val Gly Pro Ile Asp Phe Ser Thr Ile Ala Ile Gln His Ser Lys Asp168016851690GCA TCT TAT ACC AAG GCC CTT AAG TTA TTT GAA GAT AAA GAA CTT CAG 5316Ala Ser Tyr Thr Lys Ala Leu Lys Leu Phe Glu Asp Lys Glu Leu Gln169517001705TGG ACC TTC ATA ATG CTG ACC TAC CTG AAT AAC ACA CTG GTA GAA GAT 5364Trp Thr Phe Ile Met Leu Thr Tyr Leu Asn Asn Thr Leu Val Glu Asp1710171517201725TGT GTC AAA GTT CGA TCA GCA GCT GTT ACC TGT TTG AAA AAC ATT TTA 5412Cys Val Lys Val Arg Ser Ala Ala Val Thr Cys Leu Lys Asn Ile Leu173017351740GCC ACA AAG ACT GGA CAT AGT TTC TGG GAG ATT TAT AAG ATG ACA ACA 5460Ala Thr Lys Thr Gly His Ser Phe Trp Glu Ile Tyr Lys Met Thr Thr174517501755GAT CCA ATG CTG GCC TAT CTA CAG CCT TTT AGA ACA TCA AGA AAA AAG 5508Asp Pro Met Leu Ala Tyr Leu Gln Pro Phe Arg Thr Ser Arg Lys Lys176017651770TTT TTA GAA GTA CCC AGA TTT GAC AAA GAA AAC CCT TTT GAA GGC CTG 5556Phe Leu Glu Val Pro Arg Phe Asp Lys Glu Asn Pro Phe Glu Gly Leu177517801785GAT GAT ATA AAT CTG TGG ATT CCT CTA AGT GAA AAT CAT GAC ATT TGG 5604Asp Asp Ile Asn Leu Trp Ile Pro Leu Ser Glu Asn His Asp Ile Trp1790179518001805ATA AAG ACA CTG ACT TGT GCT TTT TTG GAC AGT GGA GGC ACA AAA TGT 5652Ile Lys Thr Leu Thr Cys Ala Phe Leu Asp Ser Gly Gly Thr Lys Cys181018151820GAA ATT CTT CAA TTA TTA AAG CCA ATG TGT GAA GTG AAA ACT GAC TTT 5700Glu Ile Leu Gln Leu Leu Lys Pro Met Cys Glu Val Lys Thr Asp Phe182518301835TGT CAG ACT GTA CTT CCA TAC TTG ATT CAT GAT ATT TTA CTC CAA GAT 5748Cys Gln Thr Val Leu Pro Tyr Leu Ile His Asp Ile Leu Leu Gln Asp184018451850ACA AAT GAA TCA TGG AGA AAT CTG CTT TCT ACA CAT GTT CAG GGA TTT 5796Thr Asn Glu Ser Trp Arg Asn Leu Leu Ser Thr His Val Gln Gly Phe185518601865TTC ACC AGC TGT CTT CGA CAC TTC TCG CAA ACG AGC CGA TCC ACA ACC 5844Phe Thr Ser Cys Leu Arg His Phe Ser Gln Thr Ser Arg Ser Thr Thr1870187518801885CCT GCA AAC TTG GAT TCA GAG TCA GAG CAC TTT TTC CGA TGC TGT TTG 5892Pro Ala Asn Leu Asp Ser Glu Ser Glu His Phe Phe Arg Cys Cys Leu189018951900GAT AAA AAA TCA CAA AGA ACA ATG CTT GCT GTT GTG GAC TAC ATG AGA 5940Asp Lys Lys Ser Gln Arg Thr Met Leu Ala Val Val Asp Tyr Met Arg190519101915AGA CAA AAG AGA CCT TCT TCA GGA ACA ATT TTT AAT GAT GCT TTC TGG 5988Arg Gln Lys Arg Pro Ser Ser Gly Thr Ile Phe Asn Asp Ala Phe Trp192019251930CTG GAT TTA AAT TAT CTA GAA GTT GCC AAG GTA GCT CAG TCT TGT GCT 6036Leu Asp Leu Asn Tyr Leu Glu Val Ala Lys Val Ala Gln Ser Cys Ala193519401945GCT CAC TTT ACA GCT TTA CTC TAT GCA GAA ATC TAT GCA GAT AAG AAA 6084Ala His Phe Thr Ala Leu Leu Tyr Ala Glu Ile Tyr Ala Asp Lys Lys1950195519601965AGT ATG GAT GAT CAA GAG AAA AGA AGT CTT GCA TTT GAA GAA GGA AGC 6132Ser Met Asp Asp Gln Glu Lys Arg Ser Leu Ala Phe Glu Glu Gly Ser197019751980CAG AGT ACA ACT ATT TCT AGC TTG AGT GAA AAA AGT AAA GAA GAA ACT 6180Gln Ser Thr Thr Ile Ser Ser Leu Ser Glu Lys Ser Lys Glu Glu Thr198519901995GGA ATA AGT TTA CAG GAT CTT CTC TTA GAA ATC TAC AGA AGT ATA GGG 6228Gly Ile Ser Leu Gln Asp Leu Leu Leu Glu Ile Tyr Arg Ser Ile Gly200020052010GAG CCA GAT AGT TTG TAT GGC TGT GGT GGA GGG AAG ATG TTA CAA CCC 6276Glu Pro Asp Ser Leu Tyr Gly Cys Gly Gly Gly Lys Met Leu Gln Pro201520202025ATT ACT AGA CTA CGA ACA TAT GAA CAC GAA GCA ATG TGG GGC AAA GCC 6324Ile Thr Arg Leu Arg Thr Tyr Glu His Glu Ala Met Trp Gly Lys Ala2030203520402045CTA GTA ACA TAT GAC CTC GAA ACA GCA ATC CCC TCA TCA ACA CGC CAG 6372Leu Val Thr Tyr Asp Leu Glu Thr Ala Ile Pro Ser Ser Thr Arg Gln205020552060GCA GGA ATC ATT CAG GCC TTG CAG AAT TTG GGA CTC TGC CAT ATT CTT 6420Ala Gly Ile Ile Gln Ala Leu Gln Asn Leu Gly Leu Cys His Ile Leu206520702075TCC GTC TAT TTA AAA GGA TTG GAT TAT GAA AAT AAA GAC TGG TGT CCT 6468Ser Val Tyr Leu Lys Gly Leu Asp Tyr Glu Asn Lys Asp Trp Cys Pro208020852090GAA CTA GAA GAA CTT CAT TAC CAA GCA GCA TGG AGG AAT ATG CAG TGG 6516Glu Leu Glu Glu Leu His Tyr Gln Ala Ala Trp Arg Asn Met Gln Trp209521002105GAC CAT TGC ACT TCC GTC AGC AAA GAA GTA GAA GGA ACC AGT TAC CAT 6564Asp His Cys Thr Ser Val Ser Lys Glu Val Glu Gly Thr Ser Tyr His2110211521202125GAA TCA TTG TAC AAT GCT CTA CAA TCT CTA AGA GAC AGA GAA TTC TCT 6612Glu Ser Leu Tyr Asn Ala Leu Gln Ser Leu Arg Asp Arg Glu Phe Ser213021352140ACA TTT TAT GAA AGT CTC AAA TAT GCC AGA GTA AAA GAA GTG GAA GAG 6660Thr Phe Tyr Glu Ser Leu Lys Tyr Ala Arg Val Lys Glu Val Glu Glu214521502155ATG TGT AAG CGC AGC CTT GAG TCT GTG TAT TCG CTC TAT CCC ACA CTT 6705Met Cys Lys Arg Ser Leu Glu Ser Val Tyr Ser Leu Tyr Pro Thr Leu216021652170AGC AGG TTG CAG GCC ATT GGA GAG CTG GAA AGC ATT GGG GAG CTT TTC 6756Ser Arg Leu Gln Ala Ile Gly Glu Leu Glu Ser Ile Gly Glu Leu Phe217521802185TCA AGA TCA GTC ACA CAT AGA CAA CTC TCT GAA GTA TAT ATT AAG TGG 6804Ser Arg Ser Val Thr His Arg Gln Leu Ser Glu Val Tyr Ile Lys Trp2190219522002205CAG AAA CAC TCC CAG CTT CTC AAG GAC AGT GAT TTT AGT TTT CAG GAG 6852Gln Lys His Ser Gln Leu Leu Lys Asp Ser Asp Phe Ser Phe Gln Glu221022152220CCT ATC ATG GCT CTA CGC ACA GTC ATT TTG GAG ATC CTG ATG GAA AAG 6900Pro Ile Met Ala Leu Arg Thr Val Ile Leu Glu Ile Leu Met Glu Lys222522302235GAA ATG GAC AAC TCA CAA AGA GAA TGT ATT AAG GAC ATT CTC ACC AAA 6948Glu Met Asp Asn Ser Gln Arg Glu Cys Ile Lys Asp Ile Leu Thr Lys224022452250CAC CTT GTA GAA CTC TCT ATA CTG GCC AGA ACT TTC AAG AAC ACT CAG 6996His Leu Val Glu Leu Ser Ile Leu Ala Arg Thr Phe Lys Asn Thr Gln225522602265CTC CCT GAA AGG GCA ATA TTT CAA ATT AAA CAG TAC AAT TCA GTT AGC 7044Leu Pro Glu Arg Ala Ile Phe Gln Ile Lys Gln Tyr Asn Ser Val Ser2270227522802285TGT GGA GTC TCT GAG TGG CAG CTG GAA GAA GCA CAA GTA TTC TGG GCA 7092Cys Gly Val Ser Glu Trp Gln Leu Glu Glu Ala Gln Val Phe Trp Ala229022952300AAA AAG GAG CAG AGT CTT GCC CTG AGT ATT CTC AAG CAA ATG ATC AAG 7140Lys Lys Glu Gln Ser Leu Ala Leu Ser Ile Leu Lys Gln Met Ile Lys230523102315AAG TTG GAT GCC AGC TGT GCA GCG AAC AAT CCC AGC CFA AAA CTT ACA 7188Lys Leu Asp Ala Ser Cys Ala Ala Asn Asn Pro Ser Leu Lys Leu Thr232023252330TAC ACA GAA TGT CTG AGG GTT TGT GGC AAC TGG TTA GCA GAA ACG TGC 7236Tyr Thr Glu Cys Leu Arg Val Cys Gly Asn Trp Leu Ala Glu Thr Cys233523402345TTA GAA AAT CCT GCG GTC ATC ATG CAG ACC TAT CTA GAA AAG GCA GTA 7284Leu Glu Asn Pro Ala Val Ile Met Gln Thr Tyr Leu Glu Lys Ala Val2350235523602365GAA GTT GCT GGA AAT TAT GAT GGA GAA AGT AGT GAT GAG CTA AGA AAT 7332Glu Val Ala Gly Asn Tyr Asp Gly Glu Ser Ser Asp Glu Leu Arg Asn237023752380GGA AAA ATG AAG GCA TTT CTC TCA TTA GCC CGG TTT TCA GAT ACT CAA 7380Gly Lys Met Lys Ala Phe Leu Ser Leu Ala Arg Phe Ser Asp Thr Gln238523902395TAC CAA AGA ATT GAA AAC TAC ATG AAA TCA TCG GAA TTT GAA AAC AAG 7428Tyr Gln Arg Ile Glu Asn Tyr Met Lys Ser Ser Glu Phe Glu Asn Lys240024052410CAA GCT CTC CTG AAA AGA GCC AAA GAG GAA GTA GGT CTC CTT AGG GAA 7476Gln Ala Leu Leu Lys Arg Ala Lys Glu Glu Val Gly Leu Leu Arg Glu241524202425CAT AAA ATT CAG ACA AAC AGA TAC ACA GTA AAG GTT CAG CGA GAG CTG 7524His Lys Ile Gln Thr Asn Arg Tyr Thr Val Lys Val Gln Arg Glu Leu2430243524402445GAG TTG GAT GAA TTA GCC CTG CGT GCA CTG AAA GAG GAT CGT AAA CGC 7572Glu Leu Asp Glu Leu Ala Leu Arg Ala Leu Lys Glu Asp Arg Lys Arg245024552460TTC TTA TGT AAA GCA GTT GAA AAT TAT ATC AAC TGC TTA TTA AGT GGA 7620Phe Leu Cys Lys Ala Val Glu Asn Tyr Ile Asn Cys Leu Leu Ser Gly246524702475GAA GAA CAT GAT ATG TGG GTA TTC CGG CTT TGT TCC CTC TGG CTT GAA 7668Glu Glu His Asp Met Trp Val Phe Arg Leu Cys Ser Leu Trp Leu Glu248024852490AAT TCT GGA GTT TCT GAA GTC AAT GGC ATG ATG AAG AGA GAC GGA ATG 7716Asn Ser Gly Val Ser Glu Val Asn Gly Met Met Lys Arg Asp Gly Met249525002505AAG ATT CCA ACA TAT AAA TTT TTG CCT CTT ATG TAC CAA TTG GCT GCT 7764Lys Ile Pro Thr Tyr Lys Phe Leu Pro Leu Met Tyr Gln Leu Ala Ala2510251525202525AGA ATG GGG ACC AAG ATG ATG GGA GGC CTA GGA TTT CAT GAA GTC CTC 7812Arg Met Gly Thr Lys Met Met Gly Gly Leu Gly Phe His Glu Val Leu253025352540AAT AAT CTA ATC TCT AGA ATT TCA ATG GAT CAC CCC CAT CAC ACT TTG 7860Asn Asn Leu Ile Ser Arg Ile Ser Met Asp His Pro His His Thr Leu254525502555TTT ATT ATA CTG GCC TTA GCA AAT GCA AAC AGA GAT GAA TTT CTG ACT 7908Phe Ile Ile Leu Ala Leu Ala Asn Ala Asn Arg Asp Glu Phe Leu Thr256025652570AAA CCA GAG GTA GCC AGA AGA AGC AGA ATA ACT AAA AAT GTG CCT AAA 7956Lys Pro Glu Val Ala Arg Arg Ser Arg Ile Thr Lys Asn Val Pro Lys257525802585CAA AGC TCT CAG CTT GAT GAG GAT CGA ACA GAG GCT GCA AAT AGA ATA 8004Gln Ser Ser Gln Leu Asp Glu Asp Arg Thr Glu Ala Ala Asn Arg Ile2590259526002605ATA TGT ACT ATC AGA AGT AGG AGA CCT CAG ATG GTC AGA AGT GTT GAG 8052Ile Cys Thr Ile Arg Ser Arg Arg Pro Gln Met Val Arg Ser Val Glu261026152620GCA CTT TGT GAT GCT TAT ATT ATA TTA GCA AAC TTA GAT GCC ACT CAG 8100Ala Leu Cys Asp Ala Tyr Ile Ile Leu Ala Asn Leu Asp Ala Thr Gln262526302635TGG AAG ACT CAG AGA AAA GGC ATA AAT ATT CCA GCA GAC CAG CCA ATT 8148Trp Lys Thr Gln Arg Lys Gly Ile Asn Ile Pro Ala Asp Gln Pro Ile264026452650ACT AAA CTT AAG AAT TTA GAA GAT GTT GTT GTC CCT ACT ATG GAA ATT 8196Thr Lys Leu Lys Asn Leu Glu Asp Val Val Val Pro Thr Met Glu Ile265526602665AAG GTG GAC CAC ACA GGA GAA TAT GGA AAT CTG GTG ACT ATA CAG TCA 8244Lys Val Asp His Thr Gly Glu Tyr Gly Asn Leu Val Thr Ile Gln Ser2670267526802685TTT AAA GCA GAA TTT CGC TTA GCA GGA GGT GTA AAT TTA CCA AAA ATA 8292Phe Lys Ala Glu Phe Arg Leu Ala Gly Gly Val Asn Leu Pro Lys Ile269026952700ATA GAT TGT GTA GGT TCC GAT GGC AAG GAG AGG AGA CAG CTT GTT AAG 8340Ile Asp Cys Val Gly Ser Asp Gly Lys Glu Arg Arg Gln Leu Val Lys270527102715GGC CGT GAT GAC CTG AGA CAA GAT GCT GTC ATG CAA CAG GTC TTC CAG 8388Gly Arg Asp Asp Leu Arg Gln Asp Ala Val Met Gln Gln Val Phe Gln272027252730ATG TGT AAT ACA TTA CTG CAG AGA AAC ACG GAA ACT AGG AAG AGG AAA 8436Met Cys Asn Thr Leu Leu Gln Arg Asn Thr Glu Thr Arg Lys Arg Lys273527402745TTA ACT ATC TGT ACT TAT AAG GTG GTT CCC CTC TCT CAG CGA AGT GGT 8484Leu Thr Ile Cys Thr Tyr Lys Val Val Pro Leu Ser Gln Arg Ser Gly2750275527602765GTT CTT GAA TGG TGC ACA GGA ACT GTC CCC ATT GGT GAA TTT CTT GTT 8532Val Leu Glu Trp Cys Thr Gly Thr Val Pro Ile Gly Glu Phe Leu Val277027752780AAC AAT GAA GAT GGT GCT CAT AAA AGA TAC AGG CCA AAT GAT TTC AGT 8580Asn Asn Glu Asp Gly Ala His Lys Arg Tyr Arg Pro Asn Asp Phe Ser278527902795GCC TTT CAG TGC CAA AAG AAA ATG ATG GAG GTG CAA AAA AAG TCT TTT 8628Ala Phe Gln Cys Gln Lys Lys Met Met Glu Val Gln Lys Lys Ser Phe280028052810GAA GAG AAA TAT GAA GTC TTC ATG GAT GTT TGC CAA AAT TTT CAA CCA 8676Glu Glu Lys Tyr Glu Val Phe Met Asp Val Cys Gln Asn Phe Gln Pro281528202825GTT TTC CGT TAC TTC TGC ATG GAA AAA TTC TTG GAT CCA GCT ATT TGG 8724Val Phe Arg Tyr Phe Cys Met Glu Lys Phe Leu Asp Pro Ala Ile Trp2830283528402845TTT GAG AAG CGA TTG GCT TAT ACG CGC AGT GTA GCT ACT TCT TCT ATT 8772Phe Glu Lys Arg Leu Ala Tyr Thr Arg Ser Val Ala Thr Ser Ser Ile285028552860GTT GGT TAC ATA CTT GGA CTT GGT GAT AGA CAT GTA CAG AAT ATC TTG 8820Val Gly Tyr Ile Leu Gly Leu Gly Asp Arg His Val Gln Asn Ile Leu286528702875ATA AAT GAG CAG TCA GCA GAA CTT GTA CAT ATA GAT CTA GGT GTT GCT 8868Ile Asn Glu Gln Ser Ala Glu Leu Val His Ile Asp Leu Gly Val Ala288028852890TTT GAA CAG GGC AAA ATC CTT CCT ACT CCT GAG ACA GTT CCT TTT AGA 8916Phe Glu Gln Gly Lys Ile Leu Pro Thr Pro Glu Thr Val Pro Phe Arg289529002905CTC ACC AGA GAT ATT GTG GAT GGC ATG GGC ATT ACG GGT GTT GAA GGT 8964Leu Thr Arg Asp Ile Val Asp Gly Met Gly Ile Thr Gly Val Glu Gly2910291529202925GTC TTC AGA AGA TGC TGT GAG AAA ACC ATG GAA GTG ATG AGA AAC TCT 9012Val Phe Arg Arg Cys Cys Glu Lys Thr Met Glu Val Met Arg Asn Ser293029352940CAG GAA ACT CTG TTA ACC ATT GTA GAG GTC CTT CTA TAT GAT CCA CTC 9060Gln Glu Thr Leu Leu Thr Ile Val Glu Val Leu Leu Tyr Asp Pro Leu294529502955TTT GAC TGG ACC ATG AAT CCT TTG AAA GCT TTG TAT TTA CAG CAG AGG 9108Phe Asp Trp Thr Met Asn Pro Leu Lys Ala Leu Tyr Leu Gln Gln Arg296029652970CCG GAA GAT GAA ACT GAG CTT CAC CCT ACT CTG AAT GCA GAT GAC CAA 9156Pro Glu Asp Glu Thr Glu Leu His Pro Thr Leu Asn Ala Asp Asp Gln297529802985GAA TGC AAA CGA AAT CTC AGT GAT ATT GAC CAG AGT TTC GAC AAA GTA 9204Glu Cys Lys Arg Asn Leu Ser Asp Ile Asp Gln Sar Phe Asp Lys Val2990299530003005GCT GAA CGT GTC TTA ATG AGA CTA CAA GAG AAA CTG AAA GGA GTG GAA 9252Ala Glu Arg Val Leu Met Arg Leu Gln Glu Lys Leu Lys Gly Val Glu301030153020GAA GGC ACT GTG CTC AGT GTT GGT GGA CAG GTG AAT TTG CTC ATA CAG 9300Glu Gly Thr Val Leu Ser Val Gly Gly Gln Val Asn Leu Leu Ile Gln302530303035CAG GCC ATA GAC CCC AAA AAT CTC AGC CGA CTT TTC CCA GGA TGG AAA 9348Gln Ala Ile Asp Pro Lys Asn Leu Ser Arg Leu Phe Pro Gly Trp Lys304030453050GCT TGG GTG TGATCTTCAG TATATGAATT ACCCTTTC 9385Ala Trp Val3055(2)SEQ ID NO35的说明(i)序列特征(A)长度3056个氨基酸(B)类型氨基酸(D)拓扑结构线性(ii)分子类型蛋白(xi)序列描述SEQ ID NO35Met Ser Leu Val Leu Asn Asp Leu Leu Ile Cys Cys Arg Gln Leu Glu1 5 10 15His Asp Arg Ala Thr Glu Arg Lys Lys Glu Val Glu Lys Phe Lys Arg20 25 30Leu Ile Arg Asp Pro Glu Thr Ile Lys His Leu Asp Arg His Ser Asp35 40 45Ser Lys Gln Gly Lys Tyr Leu Asn Trp Asp Ala Val Phe Arg Phe Leu50 55 60Gln Lys Tyr Ile Gln Lys Glu Thr Glu Cys Leu Arg Ile Ala Lys Pro65 70 75 80Asn Val Ser Ala Ser Thr Gln Ala Ser Arg Gln Lys Lys Met Gln Glu85 90 95Ile Ser Ser Leu Val Lys Tyr Phe Ile Lys Cys Ala Asn Arg Arg Ala100 105 110Pro Arg Leu Lys Cys Gln Glu Leu Leu Asn Tyr Ile Met Asp Thr Val115 120 125Lys Asp Ser Ser Asn Gly Ala Ile Tyr Gly Ala Asp Cys Ser Asn Ile130 135 140Leu Leu Lys Asp Ile Leu Ser Val Arg Lys Tyr Trp Cys Glu Ile Ser145 150 155 160Gln Gln Gln Trp Leu Glu Leu Phe Ser Val Tyr Phe Arg Leu Tyr Leu165 170 175Lys Pro Ser Gln Asp Val His Arg Val Leu Val Ala Arg Ile Ile His180 185 190Ala Val Thr Lys Gly Cys Cys Ser Gln Thr Asp Gly Leu Asn Ser Lys195 200 205Phe Leu Asp Phe Phe Ser Lys Ala Ile Gln Cys Ala Arg Gln Glu Lys210 215 220Ser Ser Ser Gly Leu Asn His Ile Leu Ala Ala Leu Thr Ile Phe Leu225 230 235 240Lys Thr Leu Ala Val Asn Phe Arg Ile Arg Val Cys Glu Leu Gly Asp245 250 255Glu Ile Leu Pro Thr Leu Leu Tyr Ile Trp Thr Gln His Arg Leu Asn260 265 270Asp Ser Leu Lys Glu Val Ile Ile Glu Leu Phe Gln Leu Gln Ile Tyr275 280 285Ile His His Pro Lys Gly Ala Lys Thr Gln Glu Lys Gly Ala Tyr Glu290 295 300Ser Thr Lys Trp Arg Ser Ile Leu Tyr Asn Leu Tyr Asp Leu Leu Val305 310 315 320Asn Glu Ile Ser His Ile Gly Ser Arg Gly Lys Tyr Ser Ser Gly Phe325 330 335Arg Asn Ile Ala Val Lys Glu Asn Leu Ile Glu Leu Met Ala Asp Ile340 345 350Cys His Gln Val Phe Asn Glu Asp Thr Arg Ser Leu Glu Ile Ser Gln355 360 365Ser Tyr Thr Thr Thr Gln Arg Glu Ser Ser Asp Tyr Ser Val Pro Cys370 375 380Lys Arg Lys Lys Ile Glu Leu Gly Trp Glu Val Ile Lys Asp His Leu385 390 395 400Gln Lys Ser Gln Asn Asp Phe Asp Leu Val Pro Trp Leu Gln Ile Ala405 410 415Thr Gln Leu Ile Ser Lys Tyr Pro Ala Ser Leu Pro Asn Cys Glu Leu420 425 430Ser Pro Leu Leu Met Ile Leu Ser Gln Leu Leu Pro Gln Gln Arg His435 440 445Gly Glu Arg Thr Pro Tyr Val Leu Arg Cys Leu Thr Glu Val Ala Leu450 455 460Cys Gln Asp Lys Arg Ser Asn Leu Glu Ser Ser Gln Lys Ser Asp Leu465 470 475 480Leu Lys Leu Trp Asn Lys Ile Trp Cys Ile Thr Phe Arg Gly Ile Ser485 490 495Ser Glu Gln Ile Gln Ala Glu Asn Phe Gly Leu Leu Gly Ala Ile Ile500 505 510Gln Gly Ser Leu Val Glu Val Asp Arg Glu Phe Trp Lys Leu Phe Thr515 520 525Gly Ser Ala Cys Arg Pro Ser Cys Pro Ala Val Cys Cys Leu Thr Leu530 535 540Ala Leu Thr Thr Ser Ile Val Pro Gly Ala Val Lys Met Gly Ile Glu545 550 555 560Gln Asn Met Cys Glu Val Asn Arg Ser Phe Ser Leu Lys Glu Ser Ile565 570 575Met Lys Trp Leu Leu Phe Tyr Gln Leu Glu Gly Asp Leu Glu Asn Ser580 585 590Thr Glu Val Pro Pro Ile Leu His Ser Asn Phe Pro His Leu Val Leu595 600 605Glu Lys Ile Leu Val Ser Leu Thr Met Lys Asn Cys Lys Ala Ala Met610 615 620Asn Phe Phe Gln Ser Val Pro Glu Cys Glu His His Gln Lys Asp Lys625 630 635 640Glu Glu Leu Ser Phe Ser Glu Val Glu Glu Leu Phe Leu Gln Thr Thr645 650 655Phe Asp Lys Met Asp Phe Leu Thr Ile Val Arg Glu Cys Gly Ile Glu660 665 670Lys His Gln Ser Ser Ile Gly Phe Ser Val His Gln Asn Leu Lys Glu675 680 685Ser Leu Asp Arg Cys Leu Leu Gly Leu Ser Glu Gln Leu Leu Asn Asn690 695 700Tyr Ser Ser Glu Ile Thr Asn Ser Glu Thr Leu Val Arg Cys Ser Arg705 710 715 720Leu Leu Val Gly Val Leu Gly Cys Tyr Cys Tyr Met Gly Val Ile Ala725 730 735Glu Glu Glu Ala Tyr Lys Ser Glu Leu Phe Gln Lys Ala Asn Ser Leu740 745 750Met Gln Cys Ala Gly Glu Ser Ile Thr Leu Phe Lys Asn Lys Thr Asn755 760 765Glu Glu Phe Arg Ile Gly Ser Leu Arg Asn Met Met Gln Leu Cys Thr770 775 780Arg Cys Leu Ser Asn Cys Thr Lys Lys Ser Pro Asn Lys Ile Ala Ser785 790 795 800Gly Phe Phe Leu Arg Leu Leu Thr Ser Lys Leu Met Asn Asp Ile Ala805 810 815Asp Ile Cys Lys Ser Leu Ala Ser Phe Ile Lys Lys Pro Phe Asp Arg820 825 830Gly Glu Val Glu Ser Met Glu Asp Asp Thr Asn Gly Asn Leu Met Glu835 840 845Val Glu Asp Gln Ser Ser Met Asn Leu Phe Asn Asp Tyr Pro Asp Ser850 855 860Ser Val Ser Asp Ala Asn Glu Pro Gly Glu Ser Gln Ser Thr Ile Gly865 870 875 880Ala Ile Asn Pro Leu Ala Glu Glu Tyr Leu Ser Lys Gln Asp Leu Leu885 890 895Phe Leu Asp Met Leu Lys Phe Leu Cys Leu Cys Val Thr Thr Ala Gln900 905 910Thr Asn Thr Val Ser Phe Arg Ala Ala Asp Ile Arg Arg Lys Leu Leu915 920 925Met Leu Ile Asp Ser Ser Thr Leu Glu Pro Thr Lys Ser Leu His Leu930 935 940His Met Tyr Leu Met Leu Leu Lys Glu Leu Pro Gly Glu Glu Tyr Pro945 950 955 960Leu Pro Met Glu Asp Val Leu Glu Leu Leu Lys Pro Leu Ser Asn Val965 970 975Cys Ser Leu Tyr Arg Arg Asp Gln Asp Val Cys Lys Thr Ile Leu Asn980 985 990His Val Leu His Val Val Lys Asn Leu Gly Gln Ser Asn Met Asp Ser995 10001005Glu Asn Thr Arg Asp Ala Gln Gly Gln Phe Leu Thr Val Ile Gly Ala101010151020Phe Trp His Leu Thr Lys Glu Arg Lys Tyr Ile Phe Ser Val Arg Met1025103010351040Ala Leu Val Asn Cys Leu Lys Thr Leu Leu Glu Ala Asp Pro Tyr Ser104510501055Lys Trp Ala Ile Leu Asn Val Met Gly Lys Asp Phe Pro Val Asn Glu106010651070Val Phe Thr Gln Phe Leu Ala Asp Asn His His Gln Val Arg Met Leu107510801085Ala Ala Glu Ser Ile Asn Arg Leu Phe Gln Asp Thr Lys Gly Asp Ser109010951100Ser Arg Leu Leu Lys Ala Leu Pro Leu Lys Leu Gln Gln Thr Ala Phe1105111011151120Glu Asn Ala Tyr Leu Lys Ala Gln Glu Gly Met Arg Glu Met Ser His112511301135Ser Ala Glu Asn Pro Glu Thr Leu Asp Glu Ile Tyr Asn Arg Lys Ser114011451150Val Leu Leu Thr Leu Ile Ala Val Val Leu Ser Cys Ser Pro Ile Cys115511601165Glu Lys Gln Ala Leu Phe Ala Leu Cys Lys Ser Val Lys Glu Asn Gly117011751180Leu Glu Pro His Leu Val Lys Lys Val Leu Glu Lys Val Ser Glu Thr1185119011951200Phe Gly Tyr Arg Arg Leu Glu Asp Phe Met Ala Ser His Leu Asp Tyr120512101215Leu Val Leu Glu Trp Leu Asn Leu Gln Asp Thr Glu Tyr Asn Leu Ser122012251230Ser Phe Pro Phe Ile Leu Leu Asn Tyr Thr Asn Ile Glu Asp Phe Tyr123512401245Arg Ser Cys Tyr Lys Val Leu Ile Pro His Leu Val Ile Arg Ser His125012551260Phe Asp Glu Val Lys Ser Ile Ala Asn Gln Ile Gln Glu Asp Trp Lys1265127012751280Ser Leu Leu Thr Asp Cys Phe Pro Lys Ile Leu Val Asn Ile Leu Pro128512901295Tyr Phe Ala Tyr Glu Gly Thr Arg Asp Ser Gly Met Ala Gln Gln Arg130013051310Glu Thr Ala Thr Lys Val Tyr Asp Met Leu Lys Ser Glu Asn Leu Leu131513201325Gly Lys Gln Ile Asp His Leu Phe Ile Ser Asn Leu Pro Glu Ile Val133013351340Val Glu Leu Leu Met Thr Leu His Glu Pro Ala Asn Ser Ser Ala Ser1345135013551360Gln Ser Thr Asp Leu Cys Asp Phe Ser Gly Asp Leu Asp Pro Ala Pro136513701375Asn Pro Pro His Phe Pro Ser His Val Ile Lys Ala Thr Phe Ala Tyr138013851390Ile Ser Asn Cys His Lys Thr Lys Leu Lys Ser Ile Leu Glu Ile Leu139514001405Ser Lys Ser Pro Asp Ser Tyr Gln Lys Ile Leu Leu Ala Ile Cys Glu141014151420Gln Ala Ala Glu Thr Asn Asn Val Tyr Lys Lys His Arg Ile Leu Lys1425143014351440Ile Tyr His Leu Phe Val Ser Leu Leu Leu Lys Asp Ile Lys Ser Gly144514501455Leu Gly Gly Ala Trp Ala Phe Val Leu Arg Asp Val Ile Tyr Thr Leu146014651470Ile His Tyr Ile Asn Gln Arg Pro Ser Cys Ile Met Asp Val Ser Leu147514801485Arg Ser Phe Ser Leu Cys Cys Asp Leu Leu Ser Gln Val Cys Gln Thr149014951500Ala Val Thr Tyr Cys Lys Asp Ala Leu Glu Asn His Leu His Val Ile1505151015151520Val Gly Thr Leu Ile Pro Leu Val Tyr Glu Gln Val Glu Val Gln Lys152515301535Gln Val Leu Asp Leu Leu Lys Tyr Leu Val Ile Asp Asn Lys Asp Asn154015451550Glu Asn Leu Tyr Ile Thr Ile Lys Leu Leu Asp Pro Phe Pro Asp His155515601565Val Val Phe Lys Asp Leu Arg Ile Thr Gln Gln Lys Ile Lys Tyr Ser157015751580Arg Gly Pro Phe Ser Leu Leu Glu Glu Ile Asn His Phe Leu Ser Val1585159015951600Ser Val Tyr Asp Ala Leu Pro Leu Thr Arg Leu Glu Gly Leu Lys Asp160516101615Leu Arg Arg Gln Leu Glu Leu His Lys Asp Gln Met Val Asp Ile Met162016251630Arg Ala Ser Gln Asp Asn Pro Gln Asp Gly Ile Met Val Lys Leu Val163516401645Val Asn Leu Leu Gln Leu Ser Lys Met Ala Ile Asn His Thr Gly Glu165016551660Lys Glu Val Leu Glu Ala Val Gly Ser Cys Leu Gly Glu Val Gly Pro1665167016751680Ile Asp Phe Ser Thr Ile Ala Ile Gln His Ser Lys Asp Ala Ser Tyr168516901695Thr Lys Ala Leu Lys Leu Phe Glu Asp Lys Glu Leu Gln Trp Thr Phe170017051710Ile Met Leu Thr Tyr Leu Asn Asn Thr Leu Val Glu Asp Cys Val Lys171517201725Val Arg Ser Ala Ala Val Thr Cys Leu Lys Asn Ile Leu Ala Thr Lys173017351740Thr Gly His Ser Phe Trp Glu Ile Tyr Lys Met Thr Thr Asp Pro Met1745175017551760Leu Ala Tyr Leu Gln Pro Phe Arg Thr Ser Arg Lys Lys Phe Leu Glu176517701775Val Pro Arg Phe Asp Lys Glu Asn Pro Phe Glu Gly Leu Asp Asp Ile178017851790Asn Leu Trp Ile Pro Leu Ser Glu Asn His Asp Ile Trp Ile Lys Thr179518001805Leu Thr Cys Ala Phe Leu Asp Ser Gly Gly Thr Lys Cys Glu Ile Leu181018151820Gln Leu Leu Lys Pro Met Cys Glu Val Lys Thr Asp Phe Cys Gln Thr1825183018351840Val Leu Pro Tyr Leu Ile His Asp Ile Leu Leu Gln Asp Thr Asn Glu184518501855Ser Trp Arg Asn Leu Leu Ser Thr His Val Gln Gly Phe Phe Thr Ser186018651870Cys Leu Arg His Phe Ser Gln Thr Ser Arg Ser Thr Thr Pro Ala Asn187518801885Leu Asp Ser Glu Ser Glu His Phe Phe Arg Cys Cys Leu Asp Lys Lys189018951900Ser Gln Arg Thr Met Leu Ala Val Val Asp Tyr Met Arg Arg Gln Lys1905191019151920Arg Pro Ser Ser Gly Thr Ile Phe Asn Asp Ala Phe Trp Leu Asp Leu192519301935Asn Tyr Leu Glu Val Ala Lys Val Ala Gln Ser Cys Ala Ala His Phe194019451950Thr Ala Leu Leu Tyr Ala Glu Ile Tyr Ala Asp Lys Lys Ser Met Asp195519601965Asp Gln Glu Lys Arg Ser Leu Ala Phe Glu Glu Gly Ser Gln Ser Thr197019751980Thr Ile Ser Ser Leu Ser Glu Lys Ser Lys Glu Glu Thr Gly Ile Ser1985199019952000Leu Gln Asp Leu Leu Leu Glu Ile Tyr Arg Ser Ile Gly Glu Pro Asp200520102015Ser Leu Tyr Gly Cys Gly Gly Gly Lys Met Leu Gln Pro Ile Thr Arg202020252030Leu Arg Thr Tyr Glu His Glu Ala Met Trp Gly Lys Ala Leu Val Thr203520402045Tyr Asp Leu Glu Thr Ala Ile Pro Ser Ser Thr Arg Gln Ala Gly Ile205020552060Ile Gln Ala Leu Gln Asn Leu Gly Leu Cys His Ile Leu Ser Val Tyr2065207020752080Leu Lys Gly Leu Asp Tyr Glu Asn Lys Asp Trp Cys Pro Glu Leu Glu208520902095Glu Leu His Tyr Gln Ala Ala Trp Arg Asn Met Gln Trp Asp His Cys210021052110Thr Ser Val Ser Lys Glu Val Glu Gly Thr Ser Tyr His Glu Ser Leu211521202125Tyr Asn Ala Leu Gln Ser Leu Arg Asp Arg Glu Phe Ser Thr Phe Tyr213021352140Glu Ser Leu Lys Tyr Ala Arg Val Lys Glu Val Glu Glu Met Cys Lys2145215021552160Arg Ser Leu Glu Ser Val Tyr Ser Leu Tyr Pro Thr Leu Ser Arg Leu216521702175Gln Ala Ile Gly Glu Leu Glu Ser Ile Gly Glu Leu Phe Ser Arg Ser218021852190Val Thr His Arg Gln Leu Ser Glu Val Tyr Ile Lys Trp Gln Lys His219522002205Ser Gln Leu Leu Lys Asp Ser Asp Phe Ser Phe Gln Glu Pro Ile Met221022152220Ala Leu Arg Thr Val Ile Leu Glu Ile Leu Met Glu Lys Glu Met Asp2225223022352240Asn Ser Gln Arg Glu Cys Ile Lys Asp Ile Leu Thr Lys His Leu Val224522502255Glu Leu Ser Ile Leu Ala Arg Thr Phe Lys Asn Thr Gln Leu Pro Glu226022652270Arg Ala Ile Phe Gln Ile Lys Gln Tyr Asn Ser Val Ser Cys Gly Val227522802285Ser Glu Trp Gln Leu Glu Glu Ala Gln Val Phe Trp Ala Lys Lys Glu229022952300Gln Ser Leu Ala Leu Ser Ile Leu Lys Gln Met Ile Lys Lys Leu Asp2305231023152320Ala Ser Cys Ala Ala Asn Asn Pro Ser Leu Lys Leu Thr Tyr Thr Glu232523302335Cys Leu Arg Val Cys Gly Asn Trp Leu Ala Glu Thr Cys Leu Glu Asn234023452350Pro Ala Val Ile Met Gln Thr Tyr Leu Glu Lys Ala Val Glu Val Ala235523602365Gly Asn Tyr Asp Gly Glu Ser Ser Asp Glu Leu Arg Asn Gly Lys Met237023752380Lys Ala Phe Leu Ser Leu Ala Arg Phe Ser Asp Thr Gln Tyr Gln Arg2385239023952400Ile Glu Asn Tyr Met Lys Ser Ser Glu Phe Glu Asn Lys Gln Ala Leu240524102415Leu Lys Arg Ala Lys Glu Glu Val Gly Leu Leu Arg Glu His Lys Ile242024252430Gln Thr Asn Arg Tyr Thr Val Lys Val Gln Arg Glu Leu Glu Leu Asp243524402445Glu Leu Ala Leu Arg Ala Leu Lys Glu Asp Arg lys Arg Phe Leu Cys245024552460Lys Ala Val Glu Asn Tyr Ile Asn Cys Leu Leu Ser Gly Glu Glu His2465247024752480Asp Met Trp Val Phe Arg Leu Cys Ser Leu Trp Leu Glu Asn Ser Gly248524902495Val Ser Glu Val Asn Gly Met Met Lys Arg Asp Gly Met Lys Ile Pro250025052510Thr Tyr Lys Phe Leu Pro Leu Met Tyr Gln Leu Ala Ala Arg Met Gly251525202525Thr Lys Met Met Gly Gly Leu Gly Phe His Glu Val Leu Asn Asn Leu253025352540Ile Ser Arg Ile Ser Met Asp His Pro His His Thr Leu Phe Ile Ile2545255025552560Leu Ala Leu Ala Asn Ala Asn Arg Asp Glu Phe Leu Thr Lys Pro Glu256525702575Val Ala Arg Arg Ser Arg Ile Thr Lys Asn Val Pro Lys Gln Ser Ser258025852590Gln Leu Asp Glu Asp Arg Thr Glu Ala Ala Asn Arg Ile Ile Cys Thr259526002605Ile Arg Ser Arg Arg Pro Gln Met Val Arg Ser Val Glu Ala Leu Cys261026152620Asp Ala Tyr Ile Ile Leu Ala Asn Leu Asp Ala Thr Gln Trp Lys Thr2625263026352640Gln Arg Lys Gly Ile Asn Ile Pro Ala Asp Gln Pro Ile Thr Lys Leu264526502655Lys Asn Leu Glu Asp Val Val Val Pro Thr Met Glu Ile Lys Val Asp266026652670His Thr Gly Glu Tyr Gly Asn Leu Val Thr Ile Gln Ser Phe Lys Ala267526802685Glu Phe Arg Leu Ala Gly Gly Val Asn Leu Pro Lys Ile Ile Asp Cys269026952700Val Gly Ser Asp Gly Lys Glu Arg Arg Gln Leu Val Lys Gly Arg Asp2705271027152720Asp Leu Arg Gln Asp Ala Val Met Gln Gln Val Phe Gln Met Cys Asn272527302735Thr Leu Leu Gln Arg Asn Thr Glu Thr Arg Lys Arg Lys Leu Thr Ile274027452750Cys Thr Tyr Lys Val Val Pro Leu Ser Gln Arg Ser Gly Val Leu Glu275527602765Trp Cys Thr Gly Thr Val Pro Ile Gly Glu Phe Leu Val Asn Asn Glu277027752780Asp Gly Ala His Lys Arg Tyr Arg Pro Asn Asp Phe Ser Ala Phe Gln2785279027952800Cys Gln Lys Lys Met Met Glu Val Gln Lys Lys Ser Phe Glu Glu Lys280528102815Tyr Glu Val Phe Met Asp Val Cys Gln Asn Phe Gln Pro Val Phe Arg282028252830Tyr Phe Cys Met Glu Lys Phe Leu Asp Pro Ala Ile Trp Phe Glu Lys283528402845Arg Leu Ala Tyr Thr Arg Ser Val Ala Thr Ser Ser Ile Val Gly Tyr285028552860Ile Leu Gly Leu Gly Asp Arg His Val Gln Asn Ile Leu Ile Asn Glu2865287028752880Gln Ser Ala Glu Leu Val His Ile Asp Leu Gly Val Ala Phe Glu Gln288528902895Gly Lys Ile Leu Pro Thr Pro Glu Thr Val Pro Phe Arg Leu Thr Arg290029052910Asp Ile Val Asp Gly Met Gly Ile Thr Gly Val Glu Gly Val Phe Arg291529202925Arg Cys Cys Glu Lys Thr Met Glu Val Met Arg Asn Ser Gln Glu Thr293029352940Leu Leu Thr Ile Val Glu Val Leu Leu Tyr Asp Pro Leu Phe Asp Trp2945295029552960Thr Met Asn Pro Leu Lys Ala Leu Tyr Leu Gln Gln Arg Pro Glu Asp296529702975Glu Thr Glu Leu His Pro Thr Leu Asn Ala Asp Asp Gln Glu Cys Lys298029852990Arg Asn Leu Ser Asp Ile Asp Gln Ser Phe Asp Lys Val Ala Glu Arg299530003005Val Leu Met Arg Leu Gln Glu Lys Leu Lys Gly Val Glu Glu Gly Thr301030153020Val Leu Ser Val Gly Gly Gin Val Asn Leu Leu Ile Gln Gln Ala Ile3025303030353040Asp Pro Lys Asn Leu Ser Arg Leu Phe Pro Gly Trp Lys Ala Trp Val304530503055(2)SEQ ID NO36的说明(i)序列特征(A)长度19个氨基酸(B)类型氨基酸(D)拓扑结构线性(ii)分子类型肽(xi)序列描述SEQ ID NO36Met Ser Gly Gly Ser Ser Cys Gln Thr Pro Ser Arg Ala Ile Pro Ala1 5 10 15Thr Arg Arg(2)SEQ ID NO37的说明(i)序列特征(A)长度21个氨基酸(B)类型氨基酸(D)拓扑结构线性(ii)分子类型肽(xi)序列描述SEQ ID NO37Gly Asp Tyr Ser Thr Thr Pro Gly Gly Thr Leu Phe Ser Thr Thr Pro1 5 10 15Gly Gly Thr Arg Arg20(2)SEQ ID NO38的说明(i)序列特征(A)长度12个氨基酸(B)类型氨基酸(D)拓扑结构线性(ii)分子类型肽(xi)序列描述SEQ ID NO38Glu Cys Arg Asn Ser Pro Val Thr Lys Thr Arg Arg1 5 10(2)SEQ ID NO39的说明(i)序列特征(A)长度12个氨基酸(B)类型氨基酸(D)拓扑结构线性(ii)分子类型肽(xi)序列描述SEQ ID NO39Gly Val Thr Ser Pro Ser Ser Asp Glu Pro Arg Arg1 5 10(2)SEQ ID NO40的说明(i)序列特征(A)长度10个氨基酸(B)类型氨基酸(D)拓扑结构线性(ii)分子类型肽(xi)序列描述SEQ ID NO40Met Glu Ala Ser Gln Ser His Leu Arg Arg1 5 10(2)SEQ ID NO41的说明(i)序列特征(A)长度12个氨基酸(B)类型氨基酸(D)拓扑结构线性(ii)分子类型肽(xi)序列描述SEQ ID NO41Arg Arg Asn Ser Pro Glu Asp Lys Arg Ala Gly Gly1 5 10(2)SEQ ID NO42的说明(i)序列特征(A)长度12个氨基酸(B)类型氨基酸(D)拓扑结构线性(ii)分子类型肽(xi)序列描述SEQ ID NO42Gly Glu Glu Ser Gln Phe Glu Met Asp Ile Arg Arg1 5 10
权利要求
1.包含编码SEQ ID NO31列出的PIK-相关激酶MCCS1α氨基酸序列的多核苷酸的纯化并分离的多核苷酸。
2.包含编码SEQ ID NO33列出的PIK-相关激酶MCCS1β氨基酸序列的多核苷酸的纯化并分离的多核苷酸。
3.权利要求1或2的多核苷酸，它为DNA。
4.权利要求3的DNA，它为cDNA。
5.由SEQ ID NO30列出的DNA序列组成的MCCS1αcDNA。
6.由SEQ ID NO32列出的DNA序列组成的MCCS1βDNA。
7.权利要求3的DNA，它为基因组DNA。
8.权利要求3的DNA的RNA转录物。
9.权利要求3的DNA，它为全部或部分化学合成的DNA。
10.一种DNA，它包含选自编码全长哺乳动物MCCS1激酶的DNAa)在严格条件下与SEQ ID NO30 DNA的非编码链杂交的DNA；b)在严格条件下与SEQ ID NO3 DNA的非编码链杂交的DNA；和c)在严格条件下与SEQ ID NO32 DNA的非编码链杂交的DNA。
11.包含权利要求3或10的DNA的载体。
12.权利要求11的载体，其中所述DNA被可行地连接到一个表达控制DNA序列上。
13.以允许MCCS1激酶在所述宿主细胞中表达的方式，用权利要求3或10的DNA稳定转化或转染的宿主细胞。
14.产生PIK相关激酶MCCS1的方法，此方法包含在适当的营养培养基中生长权利要求11的宿主细胞并从所述细胞或其生长的培养基中分离MCCS1激酶。
15.包含由SEQ ID NO31组成的PIK相关激酶MCCS1α氨基酸序列的纯化分离多肽。
16.包含由SEQ ID NO33组成的PIK相关激酶MCCS1α氨基酸序列的纯化分离多肽。
17.能特异地与PIK相关激酶MCCS1结合的多肽或肽。
18.权利要求17的抗体产物。
19.权利要求18的单克隆抗体。
20.产生权利要求19单克隆抗体的杂交瘤细胞系。
21.鉴定MCCS1激酶活性调制剂的方法，它包含步骤a)有或无被试化合物存在下，在激酶缓冲液中将MCCS1激酶样品与γ-32P-ATP和外源性激酶底物一起温育，并b)测量转移到所述底物的磷酸盐摩尔数；其中存在被试化合物情况下转移到所述底物的32P-磷酸盐摩尔数比不存在被试化合物情况下转移到所述底物的32P-磷酸盐摩尔数增加表示所述被试化合物是所述MCCS1激酶的激活剂，其中存在被试化合物情况下转移到所述底物的32P-磷酸盐摩尔数比不存在被试化合物情况下转移到所述底物的32P-磷酸盐摩尔数减少表示所述被试化合物是所述MCCS1激酶的抑制剂。
22.杂交瘤细胞系224C。
23.杂交瘤细胞系224F。
24.鉴定抑制MCCS1的化合物的方法，它包含步骤a)在基因改变的细胞中表达MCCS1，从而降低细胞对DNA损伤的敏感性，所述的敏感性与基因改变相关；b)在有或无被试调制剂化合物存在下，将步骤(a)的基因改变细胞经DNA损伤处理；c)测量细胞对DNA损伤的敏感性；并d)鉴定作为MCCS1活性的抑制剂、恢复细胞对DNA损伤敏感性的被试化合物。
25.鉴定抑制ATM的化合物的方法，它包含步骤a)在基因改变的细胞中表达ATM，从而降低细胞对DNA损伤的敏感性，所述的敏感性与基因改变有关；b)有或无被试调制剂化合物存在下，将步骤(a)的基因改变细胞经DNA损伤处理；c)测量细胞对DNA损伤的敏感性；并d)鉴定作为ATM活性抑制剂、恢复细胞对DNA损伤敏感性的被试化合物。
26.鉴定ATM激酶活性调制剂的方法，它包含步骤a)有或无被试化合物存在下，在激酶缓冲液中将ATM激酶样品与γ-32P-ATP和外源性激酶底物一起温育，并b)测量转移到所述底物的磷酸盐摩尔数；其中存在被试化合物情况下转移到所述底物的32P-磷酸盐摩尔数比不存在被试化合物情况下转移到所述底物的32P-磷酸盐摩尔数增加表示所述被试化合物是所述ATM激酶的激活剂，存在被试化合物情况下转移到所述底物的32P-磷酸盐摩尔数比不存在被试化合物情况下转移到所述底物的32P-磷酸盐摩尔数减少表示所述被试化合物是所述ATM激酶的抑制剂。
全文摘要
本发明广泛涉及编码细胞中对DNA损伤反应所必要的、细胞周期关卡磷脂酰肌醇激酶(PIK)相关蛋白的基因。这些PIK相关激酶在DMA损伤后停滞细胞周期以在有丝分裂或DNA复制起始之前使DNA修复的调节通路中是需要的。更特别地,本发明提供一种新的人细胞周期关卡PIK相关激酶MCCS1和编码MCCS1的多核苷酸序列。本发明还提供了鉴别如作为化疗和放射佐剂有用的MCCS1调制剂的方法。而且,提供了鉴别细胞周期关卡磷脂酰肌醇激酶(PIK)－相关蛋白、定为ATM的调制剂的方法。
文档编号C12N9/12GK1199420SQ96192586
公开日1998年11月18日 申请日期1996年11月18日 优先权日1995年11月16日
发明者M·F·霍艾克斯特拉, D·A·霍尔茨曼, K·S·基加恩 申请人:艾科斯有限公司