专利名称:新型化合物的制作方法
技术领域:
本发明涉及新鉴定的多肽及编码所述多肽的多核苷酸,它们在诊断中的应用,以及它们在鉴定可能作为在治疗有潜在作用的激动剂和拮抗剂的化合物中的用途,本发明还涉及所述多肽和多核苷酸的制备。本发明所述的多核苷酸及多肽还涉及具有信号序列的蛋白,该信号序列可使所述蛋白分泌于胞外或者与膜结合(下文往往统称为分泌蛋白或分泌多肽)。
背景技术:
药物发现方法由于涉及“功能基因组”学,即以基因组或基因为基础的高流通量(high throughput)生物学,而正经历一场重大变革。这种方法作为将基因和基因产物鉴定为治疗靶标的手段,迅速取代了原来以“定位克隆”为基础的方法。生物功能或遗传疾病的表型得到鉴定,接着可根据其遗传图谱位置回溯到负责基因(responsible gene)。
功能基因组学在很大程度上依赖于高流通量DNA测序技术和各种生物信息学工具,以便从现有的多种分子生物学数据库中鉴定出有潜在价值的基因序列。对鉴定和定性其它基因及其有关蛋白/多肽的需求一直都存在,这是药物发现的靶标。
那些天然分泌到血液、淋巴或其它体液中,或者分泌到细胞膜上的蛋白及多肽是研发药物的首要目标。原因在于可以相对容易地将蛋白治疗靶向它们的作用位置(体液或细胞膜)。真核细胞和原核细胞将蛋白质分泌入胞外区间的天然通道分别为内质网和内膜(Palade,1975,Science,189,347;Milstein,Brownlee,Harrison,and Mathews,1972,Nature New Biol.,239,117;Blobel,and Dobberstein,1975,J.Cell.Biol.,67,835)。反之,现在还没有发现一条将蛋白质由细胞外输入细胞质的天然通道(除了胞吐作用,即蛇毒液中毒素侵入细胞的机制外)。因此,将蛋白治疗物靶入细胞面临着巨大困难。
分泌型及膜结合型蛋白包括但不限于所有肽激素及其受体(包括但不限于胰岛素、生长激素、趋化因子、细胞因子、神经肽、整联蛋白、激肽释放酶、核纤层蛋白、黑色素、利尿钠激素、neuropsin,神经营养蛋白,垂体激素、多效蛋白(pleiotropins),前列腺素、分泌粒蛋白、选择蛋白、血小板球蛋白、胸腺素),乳腺癌及结肠癌基因产物、苗条蛋白(leptin)、肥胖基因蛋白及其受体、血清白蛋白、超过氧化物歧化酶、剪接体蛋白、7TM(跨膜)蛋白也称为G-蛋白偶联型受体、免疫球蛋白、丝氨酸蛋白酶的几个家族(包括但不限于血液凝固级联反应的蛋白、消化酶)、脱氧核糖核酸酶I等。
FDA或外国机构批准基于分泌型蛋白或膜结合蛋白的治疗物包括但不限于胰岛素、胰高血糖素、生长激素、绒毛膜促性腺素、促卵泡激素、促黄体素释放激素(luteinizing hormone)、降钙素、促肾上腺皮质激素(ACTH)、血管升压素、白细胞介素、干扰素、免疫球蛋白、乳铁传递蛋白(有多家公司销售的不同产品)、组织型纤溶酶原激活物(Alteplase,Genentech)、hyaulorindase(Wydase,Wyeth-Ayerst),α链道酶(Pulmozyme\,Genentech),Chymodiactin(chymopapain,Knoll),糖脑苷酶(Ceredase,Genzyme),链激酶(Kabikinase,Pharmacia)(Streptase,Astra)等。这表明分泌型及膜结合型蛋白质作为治疗靶标已有确证的历史。显然,需要对其它能够预防、减缓或纠正功能紊乱或疾病的分泌型及膜结合型蛋白质进行鉴定及定性,所述功能紊乱或疾病包括但不限于糖尿病、乳腺癌、前列腺癌、结肠癌及其它恶性肿瘤、高血压及低血压、肥胖症、过食症、厌食症、生长畸形、哮喘、燥狂抑郁病、痴呆、精神狂乱、智力低下、亨廷顿氏病、图雷特氏(Tourette)综合征、精神分裂症、生长发育障碍、精神发育障碍或性发育障碍、以及血液级联反应系统功能紊乱(包括导致中风(stroke)的那些功能紊乱)。本发明中含信号序列的蛋白还可以用来进一步阐明目前还未完全理解的蛋白输送机制,因而可以用作研究工具。
发明概述本发明涉及表I中列出基因的具体多肽及多核苷酸,包括用于制备它们的重组材料和方法。这类多肽和多核苷酸与治疗特定疾病的方法相关,所述疾病包括但不限于表III和V所列疾病,下文称作“本发明所述疾病”。另一方面,本发明涉及用本发明提供的材料鉴别激动剂和拮抗剂(例如,抑制剂)的方法,以及用鉴别出的化合物治疗与表I所列基因的多肽和/或多核苷酸失衡相关的病症的方法。另一方面,本发明还涉及用来检测与表I所列基因活性或水平异常有关的疾病的诊断试验。本发明另一方面涉及多肽以及多核苷酸,所述多核苷酸包括序列表中所列的任何核苷酸序列,所述多肽包括上述多核苷酸编码的多肽。另一方面,本发明还涉及包括序列表所列任一多肽序列的多肽及其制备所用的重组材料和方法。本发明另一方面还涉及使用所述多肽和多核苷酸的方法。所述使用包括治疗因本发明所述基因的表达、产量、功能和、或代谢的异常而引发的疾病、异常及紊乱(这些情况下文统称疾病),本领域技术人员能够很容易地从公开的每个所附序列与其它蛋白的同源性方面理解这些疾病。另一方面,本发明涉及用本发明提供的材料鉴定激动剂和拮抗剂的方法,以及治疗与鉴定出的化合物失衡相关的疾病的方法。本发明另一方面还涉及检测与本发明所述分泌型蛋白的活性或水平异常有关的疾病的诊断试验。
发明详述第一方面,本发明涉及表I中所列基因的多肽。所述多肽包括(a)由包括序列表中所列的一种序列的多核苷酸编码的分离的多肽,本发明中提到序列表中所列多核苷酸或多肽时,在序列表部分的序列列表中有相应参照;(b)一种分离的多肽,该多肽包括与序列表中的一种多肽序列具有至少95%,96%,97%,98%,或99%同一性的多肽序列;(c)一种分离的多肽,该多肽包括序列表中所列的多肽序列;(d)一种分离多肽,该多肽与序列表中列出的多肽序列之间具有至少95%,96%,97%,98%,或99%的同一性;(e)序列表中列出的一种多肽序列;以及(f)一种分离的多肽,该多肽具有或包括与序列表所列的多肽序列之间的同一性指数(Indentity Index)为0.95,0.96,0.97,0.98,或0.99的多肽序列;(g)(a)~(f)中所述多肽的片段及变体。
本发明多肽据信是表II中基因家族的成员。因此根据表III和V中所列的理由,它们具有治疗和诊断的价值。表I中基因的多肽及多核苷酸的生物学特性在本发明中称为表I中基因的多肽及多核苷酸的“生物学活性”。优选地,本发明多肽具有表I中基因的至少一种生物学活性。
本发明多肽还包括上述多肽的变体,其中包括所有的等位形式及剪接变体。所述多肽可以是从参考多肽通过保守或非保守的插入、缺失及取代,或其任何组合变化而来。具体优选的变体是那些以任意组合插入、取代或缺失了数个(如50~30、30~20、20~10、10~5、5~3、3~2、2~1个或1个)氨基酸的变体。
本发明多肽的优选片段包括这样的分离的多肽,该分离的多肽包括一种氨基酸序列,该序列具有来自序列表所列的一种氨基酸序列的至少30、50或100个连续氨基酸,或者该序列具有将序列表所列的一种氨基酸序列中截短或缺失至少30、50或100个连续氨基酸所得的氨基酸序列。优选片段是能介导表I中基因的多肽和多核苷酸的生物学活性的生物活性片段,包括那些具有近似活性或改良活性的片段,或者是不良活性降低的片段。还优选在动物体,尤其是人体中具有抗原性或免疫原性的片段。
可以通过肽合成技术利用本发明多肽的片段制备相应的全长多肽;因此,这些变体可以当作制备本发明全长多肽的中间体。本发明中的多肽可以是“成熟”蛋白的形式,也可以是如前体或融合蛋白等更大蛋白的一部分。通常,包括一段额外的氨基酸序列是有利的,其中所述氨基酸序列含有分泌或前导序列、前序列,有助于纯化的序列,例如多组氨酸残基,或者在重组生产过程中用来保持稳定的一段额外的氨基酸序列。
本发明多肽可以以任何适当的方式制备,例如可以从天然来源分离,从含表达系统(见下文)的基因工程宿主细胞分离,或者例如使用自动肽合成仪化学合成,或者上述方法的组合。制备所述多肽的方法为本领域技术人员所熟知。
另一方面,本发明涉及表I中所列基因的多核苷酸。这些多核苷酸包括(a)一种分离的多核苷酸,其中包含与序列表中一种多核苷酸序列之间具有至少95%,96%,97%,98%,或99%同一性的多核苷酸序列;(b)一种分离多核苷酸,其中包含序列表中所列的一种多核苷酸;(c)一种分离的多核苷酸,该多核苷酸与序列表中列出的一种多核苷酸之间具有至少95%,96%,97%,98%,或99%的同一性;(d)序列表中列出的一种分离的多核苷酸;(e)一种分离的多核苷酸,其中包含编码如下多肽序列的多核苷酸序列所述多肽序列与序列表中的一种多肽序列之间具有至少95%,96%,97%,98%,或99%的同一性;(f)一种分离的多核苷酸,其中包含编码序列表中一种多肽的多核苷酸序列;(g)一种分离的多核苷酸,其具有如下多核苷酸序列所述序列编码的多肽与序列表中一种多肽序列之间具有至少95%,96%,97%,98%,或99%的同一性;(h)一种分离的多核苷酸,该多核苷酸编码序列表中的一种多肽;(i)一种分离的多核苷酸,该多核苷酸具有或包含与序列表所列的一种多核苷酸序列之间的同一性指数为0.95,0.96,0.97,0.98,或0.99的多核苷酸序列;(j)一种分离的多核苷酸,其具有或包含编码如下多肽序列的多核苷酸序列所述多肽序列与序列表中所列的一种多肽序列之间的同一性指数为0.95,0.96,0.97,0.98,或0.99;以及上述多核苷酸的片段或变体,或者上述多核苷酸全长序列的互补多核苷酸。
本发明所述多核苷酸的优选片段包括一种分离的多核苷酸,该分离的多核苷酸含有如下核苷酸序列所述核苷酸序列具有来自序列表中所列的一种序列的至少15、30、50或100个连续核苷酸;或者所述多核苷酸序列具有从序列表的一种序列中截短或缺失了至少30、50或100个连续核苷酸所得的序列。
本发明所述多核苷酸的优选变体包括剪接变体、等位变体以及多态性,包括其有1个或多个单核苷酸多态性(SNP)的多核苷酸。
本发明所述多核苷酸还包括编码符合下述条件的多肽变体的多核苷酸即所述多肽变体包含序列表中的一种氨基酸序列,并且该氨基酸序列中以任意组合取代、缺失或添加了50-30、30-20、20-10、10-5、5-3、3-2、2-1或1个氨基酸残基。
另一方面,本发明提供了作为本发明所述DNA序列的RNA转录物的多核苷酸。因此,本发明提供了下述RNA多核苷酸以及与其互补的RNA多核苷酸(a)其包括编码序列表中一种多肽的DNA序列的RNA转录物;(b)其本身为编码序列表中一种多肽的DNA序列的RNA转录物;(c)其包括序列表中一种DNA序列的RNA转录物;或者(d)其本身是序列表中一种DNA序列的RNA转录物。
序列表中多核苷酸序列与表II中多核苷酸序列之间具有同源性。序列表中多核苷酸序列是编码序列表中多肽的cDNA序列。编码序列表中多肽的多核苷酸序列可以与序列表中多肽的编码序列相同,或者它也可以是序列表所列序列之外的序列,但由于遗传密码的丰余性(简并性),它也可以编码序列表中的多肽。序列表中所列序列的多肽与表II中基因家族的其它蛋白相关,与表II中多肽之间具有同源性和/或结构类似性。本发明所述的优选多肽及多核苷酸预计与它们的同源多肽及多核苷酸之间具有类似的生物功能/特性。另外,本发明优选的多肽及多核苷酸具有表I中所列基因的至少1种活性。
本发明所述多核苷酸可以用标准克隆及筛选技术从cDNA文库中得到,该cDNA文库源自表IV中组织的mRNA(参见,例如,Sambrook等,分子克隆实验指南,第二版,Cold Spring Harbor Laboratory Press,Cold SpringHarbor,N.Y(1989))。本发明所述多核苷酸还可以从天然来源获得,例如基因组DNA文库,或者可以用公知的和商业化的技术合成。
当将本发明所述多核苷酸用于重组生产本发明多肽时,所述多核苷酸可以包括成熟多肽的编码序列本身,或者与其它编码序列位于同一阅读框的成熟多肽的编码序列,所述其它序列例如编码前导或分泌序列、前-、或原-、或前原-蛋白序列、或其它融合肽部分的序列。例如,可以编码有助于融合多肽纯化的标记序列。在本发明该方面的特定优选实施例中,所述标记序列为六组氨酸肽,如pQE载体(Qiagen,Inc.)中提供的,以及见Gentz等,ProcNatl Acad Sci USA(1989)86821-824一文中的描述,或者为HA标签。多核苷酸也可以包括非编码的5′及3′序列,例如转录、非翻译序列,剪接及多腺苷酸化信号,核糖体结合位点及稳定mRNA的序列。
与序列表中多核苷酸序列相同或者具有足够同一性的多核苷酸可以用作cDNA及基因组DNA的杂交探针,或者作为核酸扩增反应(例如,PCR)的引物。所述探针可以用来分离编码本发明多肽的全长cDNA及基因组克隆,以及可以用来分离与序列表中序列间有高度序列相似性(通常至少为95%的同一性)的其它基因(包括编码人源平行进化同系物(paralogs)的基因以及其它物种来源的直向同系物(orthologs)及平行进化同系物的基因)的cDNA及基因组克隆。优选的探针及引物通常包括至少15个核苷酸,优选至少30个核苷酸,如果不是至少100个核苷酸,也可以为至少50个。特别优选的探针为30-50个核苷酸。特别优选的引物为20-25个核苷酸。
编码本发明多肽的多核苷酸,包括来自其它物种的同系物,可以通过包括下述步骤的方法来获得用具有序列表中序列或其片段的标记探针(优选至少15个核苷酸)在严谨条件下筛选文库,分离出含序列表中多核苷酸序列的全长cDNA及基因组克隆。所述杂交技术为本领域技术人员所熟知。优选的严谨杂交条件包括42℃下在含下列成分的溶液中温育过夜50%甲酰胺,5xSSC(150mM NaCI,15mM柠檬酸三钠)、50mM磷酸钠(pH 7.6),5xDenhardt′s溶液、10%葡聚糖硫酸酯、以及20μg/ml变性剪切后的鲑鱼精DNA;然后在约65℃用0.1xSSC洗涤滤膜。因此,本发明还包括在严谨条件下用标记探针筛选文库获得的分离的多核苷酸,优选地,该多核苷酸具有至少100个核苷酸,所述探针为序列表中序列或其片段,优选至少15个核苷酸。
本领域技术人员应该理解,很多情况下,分离的cDNA序列是不完整的,其编码多肽的区域不会一直延伸至5’末端。这是反转录酶所造成的结果,该酶本身具有低“持续合成能力”(聚合反应过程中该酶保持与模板结合的能力的一个指标),因而在第一链cDNA合成过程中不能合成mRNA模板的完整DNA拷贝。
现有数种本领域技术人员熟知的方法可以得到全长cDNA,或者延伸短cDNA,例如以cDNA末端快速扩增法(RACE)为基础的方法(参见,例如,Frohman et al.,Proc Nat Acad Sci USA 85,8998-9002,1988)。近来该技术有一些改进,以Marathon(商标名)技术(Clontech Laboratories Inc.)为代表,例如已大大简化了较长cDNA的筛选。在Marathon(商标名)技术中,从选定组织提取mRNA,从中制备cDNA,并且在每个末端都连接“衔接头(adaptor)”序列。然后,联合使用基因特异性引物和衔接头特异性寡核苷酸引物,通过核酸扩增(PCR)来扩增“丢失的”cDNA 5’末端。然后用“嵌套”引物重复PCR反应,所述嵌套引物是经设计而在扩增产物内部退火的引物(通常,一个为与衔接头序列的更偏3′侧退火的衔接头特异性引物,另一引物为与已知基因序列的更偏5′侧退火的基因特异性引物)。然后,通过DNA测序分析该反应产物,通过下述方法构建全长cDNA将产物与现有cDNA直接连接得到全长序列,或者利用新的序列信息设计5′引物进行单独的全长PCR扩增。
本发明所述重组多肽可以用本领域技术人员熟知的方法从含表达系统的遗传工程构建的宿主细胞中制备得到。因此,另一方面,本发明涉及含本发明所述一个或多个多核苷酸的表达系统,涉及用所述表达系统通过遗传工程手段构建的宿主细胞,以及涉及用重组技术制备本发明多肽。还可以以用源自本发明所述DNA构建体的RNA利用无细胞翻译系统来制备所述蛋白。
就重组制备而言,可以用遗传工程手段构建宿主细胞以导入本发明所述多核苷酸的表达系统或者其部分。可以用多种常规实验指南中描述的方法将多核苷酸引入宿主细胞,例如Davis等,Basic Methods in Molecular Biology(1986)和Sambrook等(同上)。将多核苷酸导入宿主细胞的优选方法包括,例如,磷酸钙转染、DEAE-葡聚糖介导的转染、转位(transvection)、显微注射、阳离子脂质-介导的转染、电穿孔、转导、刮擦上样(scrape loading)、弹道导入(ballistic introduction)或感染。
合适宿主的代表性实例包括细菌细胞,例如链球菌、葡萄球菌、大肠杆菌、链霉菌及枯草芽孢杆菌细胞;真菌细胞,例如酵母细胞和曲霉菌细胞;昆虫细胞例如果蝇S2和夜蛾(Spodoptera)Sf9细胞;动物细胞例如CHO、COS、HeLa、C127、3T3、BHK、HEK 293和Bowes黑色素瘤细胞;以及植物细胞。
有多种表达系统都可以使用,例如,染色体、附加体及病毒来源的系统,例如,源自下述的载体细菌质粒、噬菌体、转座子、酵母附加体、插入元件、酵母染色体元件、病毒如杆状病毒、乳多空病毒、如SV40、痘苗病毒、腺病毒、禽痘病毒、伪狂犬病毒及反转录病毒,及来源于其组合的载体,例如源自质粒及噬菌体遗传元件的载体,例如粘粒及噬菌粒。所述表达系统可以包含调控及实施表达的控制区。通常,任一能够在宿主细胞中维持、增殖或表达多核苷酸以生成多肽的系统或载体都可以使用。合适的多核苷酸序列可以通过多种熟知及常规技术中的任一种插入到表达系统,所述技术例如,Sambrook et al.,(如上)一书中描述的方法。可以将合适的分泌信号导入目的多肽从而使得翻译后的蛋白能够分泌到内质网腔、周质间隙或胞外环境。这些信号相对于所述多肽可以是内源性的,也可以是异源性信号。
如果本发明多肽的表达是为了用于筛选实验,那么通常优选在细胞表面制备所述多肽。这种情况下,可以在用于筛选实验前收获细胞。如果多肽分泌入培养基中,那么可回收培养基以回收及纯化所述多肽。如果在胞内生成,那么在回收多肽之前必须首先裂解细胞。
可以采用本领域熟知的方法从重组细胞培养物中回收和纯化本发明多肽,其中包括硫酸铵或乙醇沉淀、酸抽提、阴离子或阳离子交换层析、磷酸纤维素层析、疏水作用层析、亲和层析、羟基磷灰石层析以及凝集素层析。最优选地,用高效液相色谱来纯化。当多肽在胞内合成、分离和/或纯化过程中变性时,可以使用本领域熟知的蛋白重折叠技术重新生成活性构象。
本发明多肽可以用作诊断试剂,检测相关基因中的突变。对突变形式的基因的检测,其特征在于cDNA或基因组序列中列于序列表中的多核苷酸,且其与功能紊乱相关。本发明将提供一诊断工具,该诊断工具可以辅助诊断或明确诊断疾病或疾病易感性,所述疾病是由基因的低表达、过表达或表达在空间或时间上的变化引起。带有基因突变的个体可以通过多种本领域熟知的技术在DNA水平上检测。
用于诊断的核酸可以从受试者细胞中获得,例如从血液、尿液、唾液、组织活检或尸检材料中获得。基因组DNA可以直接用于检测,或者在分析前用PCR,优选用RT-PCR,或者用其它扩增技术进行酶性扩增。RNA或cDNA也可以以类似的方式应用。通过扩增产物与正常基因型相比大小上的变化来检测缺失和插入。通过将扩增的DNA与标记后的表1中基因的核苷酸序列杂交可检测点突变。用RNA酶消化或解链温度的差异可将错配的双螺旋体与完美匹配的序列区分。还可以以DNA片段在有或无变性试剂存在的情况下,在凝胶中电泳迁移率的改变,或者通过直接DNA测序(参见,例如,Myers et al.,Science(1985)2301242)来检测DNA序列的差异。还可以用核酸酶保护试验或者化学切割方法检测出特定位点上的序列变化,所述保护例如RNA酶及S1保护(见,Cotton et al.,Proc Natl Acad Sci USA(1985)854397-4401)。
可以构建包含表I中基因的多核苷酸序列或其片段的寡核苷酸探针阵列以实施高效筛选,例如对基因突变的高效筛选。所述阵列优选为高密度阵列或载网(grids)。阵列技术的方法为本领域熟知,具有广泛用途,并且可以用来研究分子遗传学中的多种问题,包括基因表达、基因连锁及基因变异性,参见,例如,M.Chee et al.,Science,274,610-613(1996)以及本发明引述的其它文献。
也可以通过检测多肽或mRNA表达的异常减少或增加来诊断或测定受试者对本发明所述疾病的易感性。表达的减少或增加可以用本领域熟知的任一检测多核苷酸量的方法在RNA水平上测量出来,所述方法例如,核酸扩增、如PCR、RT-PCR、RNA酶保护、Northern印迹法及其它杂交方法。用于测定蛋白,如本发明多肽在来自宿主的标本中的水平的分析技术已为本领域技术人员所熟知。所述分析方法包括放射免疫测定、竞争结合试验、Western印迹分析及ELISA试验。
因此另一方面,本发明涉及一种诊断试剂盒,其包括(a)本发明所述多核苷酸,优选序列表中的核苷酸序列,或者其片段或RNA转录体;(b)与(a)中多核苷酸互补的核苷酸序列;(c)本发明所述多肽,优选序列表中的多肽或其片段;或者(d)抗本发明多肽的抗体,优选抗序列表中的多肽的抗体。
可以理解的是,在任一所述试剂盒中,(a),(b),(c)或(d)中都包含一种基本组分。该试剂盒可以用来诊断疾病或对疾病的易感性,尤其是本发明所述疾病。
本发明所述多核苷酸序列对于染色体定位研究很有价值。序列表中的序列特异性地靶向单个人源染色体的特定位点并可与该位点杂交。在本发明的染色体上对相关序列作图是使这些序列和基因相关疾病间建立关联的重要的第一步。一旦将序列定位到确切的染色体位置,就可以将染色体上该序列的物理位置与遗传图谱资料间建立相关关系。所述资料见于,例如,V.McKusick,Mendelian Inheritance in Man(available online through JohnsHopkins University Welch Medical Library)。然后,通过连锁分析(物理邻接基因的共遗传),鉴定出已定位到同一染色体区域中的基因与疾病间的相关关系。基因组序列(基因片段等)的确切人染色体定位可以用放射杂交(RH)作图方法确定(Walter,M.Spillett,D.,Thomas,P.,Weissenbach,J.,and Goodfellow,P.,(1994)一种构建全基因组放射杂交图谱的方法,Nature Genetics 7,22-28)。大量的RH试验板(panel)获自Research Genetics(Huntsville,AL,USA)例如GeneBridge4 RH板(Hum Mol Genet 1996 Mar;5(3)339-46 A radiationhybrid map of the human genome.Gyapay G,Schmitt K,Fizames C,Jones H,Vega-Czarny N,Spillett D,Muselet D,Proud′homme JF,Dib C,Auffray C,Morissette J,Weissenbach J,Goodfellow PN)。为了用所述试验板确定基因的染色体定位,使用根据RH DNA上的目的基因设计的引物进行93次PCR反应。这些DNA中的每一个都包括维持在仓鼠背景(人/仓鼠杂交细胞系)中的随机人基因组片段。这些PCR反应得到93个分值,它们指示目的基因的PCR产物的存在与否。将这些分值与用已知位点基因组序列的PCR产物得到的分值进行比较。所述比较在该网址上进行,即http//www.genome.wi.mit.edu/。
本发明所述多核苷酸序列还是进行组织表达研究的有效工具。所述研究导致能确定本发明所述多核苷酸的表达模式,从而通过检测编码所述多肽的mRNA来指示组织中所编码的多肽的表达模式。所用的技术为本领域熟知,包括对排列在载网上的克隆进行原位杂交技术,例如cDNA微阵列杂交(Schena et al,Science,270,467-470,1995 and Shalon et al,Genome Res,6,639-645,1996)以及核苷酸扩增技术如PCR。优选的方法使用Perkin Elmer公司提供的TAQMAN(商标名)技术。这些研究的结果可以为所述多肽在生物体内的正常功能提供指示。此外,mRNA的正常表达模式与同一基因的替代形式(例如,多肽编码能力有变或具有调节性突变的那些)所编码的mRNA的表达模式间的对比研究,可以为本发明多肽的作用提供有价值的发现,或者对其在疾病中的不适当表达所起的作用提供有价值的发现。这些不适当表达可以是时间、空间或单纯量上的特性。
本发明另一方面还涉及抗体。本发明多肽或其片段,或表达它们的细胞,都可以用作免疫原,以制备针对本发明多肽具有免疫特异性的抗体。“免疫特异性”一词是指所述抗体与本发明多肽间的亲和力明显大于其与现有技术中其它相关多肽间的亲和力。
抗本发明多肽的抗体可以通过常规方法向动物,优选非人动物,施用所述多肽或含表位的片段、或细胞而获得。就制备单克隆抗体而言,任一能够通过连续细胞系培养获得抗体的技术都可以使用。实例包括杂交瘤技术(Kohler,G. and Milstein,C.,Nature(1975)256495-497)、trioma技术、人B-细胞杂交瘤技术(Kozbor et al.,Immunology Today(1983)472)以及EBV-杂交瘤技术(Cole et al.,Monoclonal Antibodies and Cancer Therapy,77-96,Alan R.Liss,Inc.,1985)。
用于制备单链抗体的技术,例如序列号为No.4,946,778的美国专利中描述的,也可以调整后用来制备抗本发明多肽的单链抗体。另外,转基因小鼠,或其它生物,包括其它哺乳动物,也可以用于表达人源化抗体。
上述抗体可以用于分离或鉴定表达所述多肽的克隆,或者通过亲和层析纯化所述多肽。抗本发明多肽的抗体也可以用来治疗本发明所述疾病。
本发明多肽及多核苷酸还可以用作疫苗。因此,另一方面,本发明涉及一种激发哺乳动物免疫应答的方法,该方法包括用足够量的本发明多肽接种哺乳动物,使所述哺乳动物产生抗体和/或T细胞免疫应答,包括,例如,产细胞因子的T细胞或细胞毒性T细胞,以使所述动物抗御疾病,而无论疾病是否已在个体中存在。哺乳动物体内的免疫应答还可以通过这样的方法来激发,该方法包括通过能指导多核苷酸表达并且能在体内编码所述多肽的载体运载本发明多肽,诱导免疫应答,产生抗体,保护所述动物免遭本发明所述疾病。上述载体施用的一种方法是将其包裹颗粒或将其它物质,使其加速进入目的细胞。所述核酸载体包括DNA、RNA、修饰后的核酸、或DNA/RNA杂合体。就用作疫苗而言,多肽或核酸载体通常以疫苗制剂(组合物)的形式提供。所述制剂可以进一步包括适当的载体。由于多肽可能在胃中被降解,所以优选通过非胃肠道途径给药(例如,皮下、肌内、静脉内、或皮内注射)。适于非胃肠道给药的制剂包括含水及不含水的无菌注射液,其中可含有抗氧化剂、缓冲液、抑菌剂以及能使制剂与受体血液等渗(instonic)的溶质;以及含水及不含水无菌悬液,其中可包括悬浮剂或增稠剂。所述制剂可以配制成单位剂量或多剂量包装,例如,密封安瓿和小瓶,以及可以冻干方式保存,只需在使用前临时加入无菌液态载体。所述疫苗制剂还可包括佐剂系统用来增强制剂的免疫原性,例如水包油系统以及其它本领域已知系统。剂量取决于疫苗的比活性,可根据常规经验容易地确定。
本发明多肽具有与1种或多种病理状态有关的1种或多种生物功能,所述病理状态具体为本发明所述疾病。因此,鉴定出能够刺激或抑制所述多肽的功能或水平的化合物是有用的。因此,另一方面,本发明提供了一种筛选能够刺激或抑制所述多肽功能或水平的化合物的方法。上述方法能够鉴定出可用于治疗及预防本发明所述疾病的激动剂或拮抗剂。可从如下多种来源鉴定上述化合物,例如,细胞、无细胞制剂、化学文库、化合物集合、以及天然产物混合物。如此鉴定出的激动剂或拮抗剂可以为天然或修饰后的所述多肽的底物、配体、受体、酶等(依情况而定);其结构或功能的模拟体(参见,Coligan et al.,Current Protocols in Immunology 1(2)Chapter 5(1991))或小分子。所述小分子优选分子量低于2,000道尔顿,更优选为300~1,000道尔顿,最优选400~700道尔顿。优选这些小分子为有机分子。
该筛选方法通过与候选化合物直接或间接连接的标记物,可以简便地检测出候选化合物与多肽、与带有所述多肽的细胞或细胞膜、或与其融合蛋白的结合。或者,所述筛选方法可以包括检测(定性或定量)候选化合物与多肽同标记竞争物(例如激动剂或拮抗剂)之间的竞争结合。另外,这些筛选方法可以使用适于带有该多肽的细胞的检测系统,测试候选化合物是否能引发由所述多肽被激发或被抑制所产生的信号。通常在有已知激动剂的情况下测定对激活作用的抑制剂,此时可观察候选化合物存在时该激动剂的活化效果。另外,筛选方法可以简单地包括将候选化合物与含本发明多肽的溶液混合,形成混合物,测量混合物中表I所列基因的活性,并且将表I所列基因的混合物的活性与不含候选化合物的对照混合物进行比较。
本发明多肽可以用于常规低容量筛选方法以及还可用于高流通量筛选(high-throughput screening)(HTS)方式。所述HTS方式不仅可以使用成熟的96孔微量滴定板,还可以使用最近出现的384孔微量滴定板,而且还可用新出现的方法,例如Schullek et al,Anal Biochem.,246,20-29,(1997)一书描述的毫微孔(nanowell)方法。
融合蛋白,例如由Fc部分和如上所述的表I中基因的多肽形成的融合蛋白,也可用于高流通量筛选试验,来鉴定本发明多肽的拮抗剂(见D.Bennettet al.,J Mol Recognition,852-58(1995);and K.Johanson et al.,J Biol Chem,270(16)9459-9471(1995))。
本发明所述的多核苷酸、多肽及抗该多肽的抗体也可以用于设计筛选方法,来检测所加入的化合物对细胞中mRNA及多肽的生产的影响。例如,可构建ELISA试验,用本领域常规方法使用单克隆及多克隆抗体测定分泌型多肽及细胞结合型多肽的水平。用该方法能从适当操作后的细胞或组织中发现可抑制或增加多肽的生产的试剂(也分别称为拮抗剂或激动剂)。
通过本领域已知的常规受体结合技术,可用本发明多肽鉴定膜结合受体或可溶性受体。这些技术包括,但不限于,配体结合及交联试验,其中所述多肽被放射性同位素(例如,125I)标记、化学修饰(例如,生物素化)、或融合到适于检测或纯化的肽序列上,然后与推定受体的来源物(细胞、细胞膜、细胞上清液、组织提取物、体液)孵育。其它方法包括生物物理学技术如表面胞质基因组共振及光谱学方法。这些筛选方法还可用于鉴定能够与多肽竞争性结合多肽受体的激动剂及拮抗剂。完成所述试验的常规技术为本领域熟知。
本发明多肽的拮抗剂的实例包括抗体或者,在某些情况下,与配体紧密相关的寡核苷酸或蛋白,所述多肽的底物,受体,酶等,例如配体、底物、受体、酶的片段等;或者可与本发明多肽结合但不能激发应答的小分子,该多肽的活性从而受到抑制。
筛选方法还涉及使用转基因技术及表I中的基因。构建转基因动物的技术已很成熟。例如,可将表I中的基因通过显微注射导入受精卵的雄性原核,通过反转录病毒转移入植入前或植入后的胚胎,或者将遗传工程修饰后的胚胎干细胞例如通过电穿孔注射入宿主胚泡。特别有用的转基因动物是所谓的“敲入(knock-in)”动物,其中该动物基因组中的动物基因被人源的等同基因所取代。敲入转基因动物可用于药物发现过程,用作靶标确认,其中所述化合物对于人靶标是特异性的。其它有用的转基因动物有所谓的“敲除(knock-out)”动物,其中与本发明多肽相应且被细胞中内源DNA序列编码的动物直向进化同系物的表达被部分或完全废除。基因敲除可以靶向特异细胞或组织,由于技术局限可能只发生在某些细胞或组织中,或者可以发生在全部,或基本上全部动物细胞中。转基因动物技术还提供了一种完整动物表达-克隆系统,其中导入的基因被表达,生成大量本发明多肽。
可用于上述方法的筛选试剂盒构成本发明的另一方面。所述筛选试剂盒包括(a)本发明所述多肽;(b)表达本发明多肽的重组细胞;(c)表达本发明多肽的细胞膜;或者(d)抗本发明多肽的抗体;所述多肽优选是序列表中所列多肽。
应该理解的是,任一种所述试剂盒中,(a),(b),(c)或(d)可以包括一基本组分。
术语表提供下列定义以便更好地理解本发明中经常出现的术语。
本发明中的“抗体”包括多克隆及单克隆抗体,嵌合、单链、及人源化抗体,以及Fab片段,包括Fab的产物或其它免疫球蛋白表达文库的产物。
“分离的”是指通过人工改变了其天然状态,即如果其是天然生成的,那么已将其从原初的环境中改变或移取出来,或者这两种情况都同时发生。例如,生物活体中天然存在的多核苷酸或多肽不是“分离的”,但是从其天然状态下的共存物中分离出来的同样的多核苷酸或多肽就是“分离的”。本发明中使用的该术语就是这个含义。另外,通过转化、基因操作或其它任一重组方法导入到生物体中的多核苷酸或多肽都是“分离的”,即使其仍存在于该生物体中,所述生物体可以是存活的或死亡的。
“分泌型蛋白的活性或者分泌型多肽的活性”或者“分泌型蛋白的生物活性或者分泌型多肽的生物活性”是指所述分泌型蛋白的代谢或生理功能,包括近似的活性或增强的活性或者减小了不需要的副作用的活性。另外还包括所述分泌蛋白的抗原活性及免疫原活性。
“分泌蛋白的基因”是指包含了所附任一核苷酸序列的多核苷酸或其等位变体和/或其互补体。
“多核苷酸”通常是指任一多核糖核酸(RNA)或多脱氧核糖核酸(DNA),可以是修饰后的或者未经修饰的RNA或DNA。“多核苷酸”包括,但不限于,单链及双链DNA,单链和双链区混合体的DNA,单链及双链RNA,以及单链和双链区混合的RNA,包含DNA和RNA的杂合分子,所述DNA和RNA可以是单链或更通常为双链或者单链与双链区的混合体。此外,“多核苷酸”还指三链区,包含RNA或DNA或者同时包含二者。术语“多核苷酸”还包括含1个或多个已修饰的碱基的DNA或RNA以及为稳定或其它原因对骨架修饰后的DNA或RNA。“修饰的”碱基包括,例如三苯甲基化的(tritylated)碱基以及肌苷等非常见碱基。可对DNA及RNA作多种修饰;因此“多核苷酸”包括自然界中常见的多核苷酸的化学、酶促或代谢修饰形式,以及病毒及细胞特有的化学形式DNA及RNA。“多核苷酸″还包括相对短的多核苷酸,通常称为寡核苷酸。
“多肽″是指含2个或多个通过肽键或修饰后的肽键彼此相连的氨基酸的任一多肽(即肽等排物(isostere))。“多肽”既可以指短链多肽,也可以指长链多肽。短链多肽通常称为肽、寡肽或寡聚体,长链多肽通常称为蛋白质。多肽可以包括除20种由基因编码的氨基酸以外的氨基酸。“多肽”包括经天然加工如翻译后加工或者经本领域熟知的化学修饰技术加工后的氨基酸序列。所述修饰在基础课本和更详尽的专著以及大量研究文献中都有详细的描述。修饰可以发生在多肽的任一位置,包括肽骨架、氨基酸侧链以及氨基或羧基末端。应该理解的是相同的修饰可以以同等程度或不同程度出现在给定多肽的数个位点。另外,给定的多肽可以包括多种类型的修饰。多肽可以是分支状的(遍在化的结果),可以是环形的,有或无分支。环形、分支状及分支环形多肽可以得自翻译后的天然加工或者可用合成方法来制备。修饰包括乙酰化、酰化、ADP-核糖基化、酰胺化、生物素化、共价连接黄素、共价连接亚铁血红素部分、共价连接核苷酸或核苷酸衍生物、共价连接脂类或脂类衍生物、共价连接磷脂酰肌醇(phosphotidylinositol)、交联、环化、形成二硫键、去甲基化、形成共价交联、生成胱氨酸、生成焦谷氨酸、甲酰化、γ-羧基化、糖基化、GPI锚定形成、羟基化、碘化、甲基化、豆蔻酰化、氧化、蛋白裂解性加工、磷酸化、异戊二烯化、外消旋化、硒代化(selenoylation)、磺化、借助转运-RNA向蛋白添加氨基酸如精氨酸化,以及遍在化(参见,例如,蛋白结构及分子特性,2nd Ed.,T.E.Creighton,W. H.Freeman and Company,New York,1993;Wold,F.,Post-translational Protein ModificationsPerspectives and Prospects,1-12,in Post-translational Covalent Modification ofProteins,B.C.Johnson,Ed.,Academic Press,New York,1983;Seifter et al.,“Analysis for protein modifications and nonprotein cofactors″,Meth Enzymol,182,626-646,1990,and Rattan etal.,“Protein SynthesisPosttranslationalModifications and Aging″,Ann NY Acad Sci,663,48-62,1992)。
多肽序列的“片段″是指比参考序列短但是基本保留了与参考多肽相同的生物功能或活性的多肽序列。多核苷酸序列的“片段″是指比序列表中所列参考序列短的多核苷酸序列。
“变体″是指这样的多肽或多核苷酸序列,它们不同于参考多核苷酸或参考多肽,但是保留了参考多核苷酸或参考多肽的基本特性。多核苷酸的常见变体在核苷酸序列上不同于参考多核苷酸。该变体的核苷酸序列的改变可能改变或不改变由所述参考多核苷酸编码的多肽的氨基酸序列。核苷酸改变导致参考序列编码的多肽中氨基酸取代、添加、缺失、融合及截短,讨论见下文。多肽的常见变体在氨基酸序列上不同于参考多肽。通常,改变是有限的,从而使参考多肽的序列与该变体的序列在整体上是十分近似的,并且多个区域是相同的。变体和参考多肽之间可因1个或多个取代、插入、缺失的任意组合而在氨基酸序列上不同。取代或插入的氨基酸残基可以由或不由遗传密码子编码。常见的保守取代包括Gly,Ala;Ala,Ile,Leu;Asp,Glu;Asn,Gln;Ser,Thr;Lys,Arg;以及Phe和Tyr。多核苷酸或多肽的变体可以是天然生成的,如等位基因,或者也可以是不知道能天然生成的变体。多核苷酸及多肽的非天然生成的变体可用诱变技术制备或直接合成。另外还包括的变体是具有1个或多个翻译后修饰的多肽,例如糖基化、磷酸化、甲基化、ADP核糖基化等。实施方案包括N-末端氨基酸的甲基化、丝氨酸及苏氨酸的磷酸化以及C-末端甘氨酸的修饰。
“等位基因″是指基因组特定座位上一个基因的2个或多个备选形式中的一种。
“多态性″是指一群体内基因组特定位置上核苷酸序列(以及编码的多肽序列,如果相关)的不同。
“单核苷酸多态性”(SNP)是指一群体内基因组的单个核苷酸位置上出现核苷酸变化。SNP可发生于基因组的一个基因内或多个基因间区域中。SNP可以用等位基因特异性扩增(ASA)来分析。这项操作需要至少3个引物。其中用到一种共同引物,它与待分析的多态性反向互补。该共同引物从多态性碱基起为50-1500bp。另外两个(或多个)引物是彼此基本相同的,但最后的3’碱基有所变动,以便与构成多态性的2个(或多个)等位基因之一匹配。然后在标本DNA上进行两个(或多个)PCR反应,每个PCR反应都使用上述共同引物和其中一种等位特异性引物。
本发明中的“剪接变体”是指来自相同的基因组DNA序列,但经历了不同的RNA剪接的的RNA分子。不同的RNA剪接发生在对初始RNA转录物进行剪接时,通常是为了除去内含子,它们导致制备出不只一种mRNA分子,其中的每一种都编码不同的氨基酸序列。剪接变体一词也指上述cDNA分子编码的蛋白质。
“同一性”是指通过序列对比测定出的两个或多个多肽序列或者是两个或多个多核苷酸序列之间的关系。通常,同一性是指在所比较的序列长度内两多肽序列之间氨基酸与氨基酸的对应性,或两多核苷酸序列之间核苷酸与核苷酸的对应性。
“%同一性”-对于不完全对应的序列,可以测定“%同一性”。通常将两种要进行比较的序列对应排列,以便得到序列间的最大相关程度。这包括为提高对应排列程度,在其中的1或两个序列中插入“间隙”。可以就每一参与比较的序列的全长来测定%同一性(称为整体对应排列),这特别适用于长度相等或非常近似的序列,或者也可以就指定长度的较短序列进行测定(称为局部对应排列),这更适用于长度不等的多个序列。
“相似性”是对两种多肽序列间相关程度作进一步更精确的测量。通常,“相似性”意指两多肽链的氨基酸间的对比,是在残基逐一对比水平上的对比,不仅涉及残基对之间的确切对应(如同一性的计算),也涉及并非确切对应的残基对,其中所述确切对应的残基对是指,其中每一残基来自参与对比的不同序列,所述并非确切对应的残基对是指,在进化的基础上,一残基可能要取代另一残基。这种可能性有一相关“分值”,可从中测算出两序列间的“%相似性”。
比较两或多序列间同一性及相似性的方法为本领域所熟知。因此例如,Wisconsin Sequence Analysis Package,版本9.1(Devereux J et al,NucleicAcids Res,12,387-395,1984,可得自Genetics Computer Group,Madison,Wisconsin,USA)中的程序,例如程序BESTFIT和GAP,可用来测定两种多核苷酸序列间的%同一性以及两种多肽序列间的%同一性和%相似性。BESTFIT使用Smith和Waterman的“局部同源性″算法(J Mol Biol,147,195-197,1981,Advances in Applied Mathematics,2,482-489,1981),找出两序列间最相似的单个区域。BESTFIT更适于比较长度上不近似的两种多核苷酸或两种多肽序列,该程序将较短序列假定为较长序列的一部分。比较过程中,GAP将两序列对应排列,根据Neddleman和Wunsch的算法(J Mol Biol,48,443-453,1970),找出“最大相似性”。GAP更适于比较近似等长的序列,期望对全长序列进行对应排列。优选地,每个程序中使用的参数“间隙权值″和“长度权值″对于多核苷酸序列分别为50和3,对于多肽序列则分别为12和4。优选地,在将待比的两序列最佳对应排列时测定%同一性和相似性。
用于测定序列间同一性和/或相似性的其它程序也为本领域所已知,例如BLAST程序家族(Altschul S F等,J Mol Biol,215,403-410,1990,AltschulS F等,Nucleic Acids Res.,25389-3402,1997,可得自National Center forBiotechnology Information(NCBI),Bethesda,Maryland,USA,也可以从NCBI在www.ncbi.nlm.nih.Gov的主页获得)和FASTA(Pearson W R,Methods inEnzymology,183,63-99,1990;Pearson W R and Lipman D J,Proc Nat AcadSci USA,85,2444-2448,1988,是Wisconsin Sequence Analysis软件包的一部分)。
优选地,使用BLOSUM62氨基酸取代矩阵(Henikoff S and Henikoff J G,Proc.Nat.Acad Sci.USA,89,10915-10919,1992)进行多肽序列对比,其中包括在对比前首先将核苷酸序列翻译为氨基酸序列。
优选地,使用BESTFIT程序测定待测多核苷酸或多肽序列与作为参考的多核苷酸或多肽序列之间的%同一性,其中将所述待测序列与所述参考序列最进行最佳对应排列,并将程序的参数设为如上所述的缺省值。
“同一性指数”是序列相关程度的度量,其可用来比较候选序列(多核苷酸或多肽)和参考序列。因此,例如,与参考多核苷酸序列之间的同一性指数为0.95的候选多核苷酸序列可认为与参考序列是相同的,只是相对于参考序列的每100个核苷酸,在候选多核苷酸序列上有平均最多达5处差异。所述差异选自至少1个核苷酸缺失、取代、包括转换和颠换、或插入。这些差异可出现在参考多核苷酸序列5′或3′末端或者两末端之间的任一位置,可以单个地散布在参考序列的核苷酸之间,或者也可以以1个或多个连续集团的方式散布在参考序列内。换句话说,为了得到与参考多核苷酸序列间同一性指数为0.95的多核苷酸序列,可以使参考序列的每100个核苷酸中有平均最多达5个缺失、取代或插入,或其任一组合,如上文所述。必要时对其它同一性指数,例如0.96,0.97,0.98和0.99的情况也可以照此办理。
类似地,就多肽而言,与参考多肽序列之间的同一性指数为0.95的候选多肽序列可认为与参考序列是相同的,只是相对于参考序列的每100个氨基酸,在候选多肽序列上有平均最多达5处差异。所述差异选自至少1个氨基酸缺失、取代、包括保守和非保守、或插入。这些差异可出现在参考多肽序列的氨基末端或羧基末端或者两末端之间的任一位置,可以单个地散布在参考序列的氨基酸之间,或者也可以以1个或多个连续集团的方式散布在参考序列内。换句话说,为了得到与参考序列间同一性指数为0.95的多肽序列,可以使参考序列的每100个氨基酸中有平均最多达5个缺失、取代或插入,或其任一组合,如上文所述。必要时对其它同一性指数,例如0.96,0.97,0.98和0.99的情况也可以照此办理。
核苷酸或氨基酸差异数与同一性指数之间的关系可以表述为na≤Xa-(Xa·I)其中,na为核苷酸或氨基酸差异的数目,xa为序列表中所列序列的核苷酸或氨基酸的总数,I为同一性指数,·为乘法运算符,且其中当xa和I的乘积为非整数时,要将其下舍为最接近的整数,然后再被xa减。
“同系物″是本领域的一个广义词汇,意指与参考序列间有很高的序列相关程度的多核苷酸或多肽序列。所述的相关程度可通过如上述测定两种序列之间的同一性和/或相似性的程度来定量。属于这一广义词汇范畴内的有“直向进化同系物″及“平行进化同系物″。“直向进化同系物″是指与另一物种中的多核苷酸或多肽功能等价的多核苷酸或多肽。“平行进化同系物″是指同一物种中功能类似的多核苷酸或多肽。
“融合蛋白″是指由两个,通常为互不相关的两个,融合基因或其片段编码的蛋白质。在一个举例中,EP-A-0 464 533-A公开了包括免疫球蛋白分子恒定区的不同部分和另一种人蛋白质或其部分的融合蛋白质。多数情况下,用免疫球蛋白Fc区域作为融合蛋白质的一部分有助于用于治疗和诊断,可以提高药物动力学特性[参见,例如,EP-A 0232 262]。另一方面,在某些用途时,在融合蛋白表达、检测及纯化后,需将Fc部分去掉。
所有出版物及参考文献,包括但不限于该说明书中引用的专利和专利申请,作为一个整体在此引入作为参考,如同每一单篇出版物或参考文献专门单独地引入作为参考。本申请请求优先权的任一专利申请也被完整引入作为参考,方式同上述出版物及参考文献。
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表III
表IV.用SybrMan检测mRNA的组织特异性的定量表达用SYBR-Green定量PCR(Applied Biosystems,Foster City,CA;参见Schmittgen T.D.et al.,Analytical Biochemistry 285194-204,2000)以及从各种人组织中制备的人cDNA测定所述基因的mRNA的组织特异性定量表达模式。使用序列表中每个基因的第一种核酸序列设计基因特异性PCR引物。域循环(Ct)定义为部分循环数,在该循环数的情况下通过剪切探针生成的报告分子荧光达到10倍于背景的域值。在序列检测系统软件预测到一个以上的PCR产物的情况下,可用Taqman进行特定的PCR扩增(如在特定基因情况下所提示的那样)。
在每种基因的第一个表中,显示了对各种人组织中身份鉴别基因(geneof identification(GOI))mRNA的两次平行检测的结果(第3列和第4列)。表中显示了每种组织RNA的两次平行检测的平均GOI mRNA拷贝数(第5列)。检测了来自每种组织RNA的18S rRNA的平均值(第6列)并用以标准化。为使每种组织具有相同的18S rRNA量(50ng),用50ng除以所测每种组织的18SrRNA的量(第6列),计算出标准化系数(第7列)。每个GOI标准化系数乘以平均mRNA拷贝数即可得到每50ng总RNA中mRNA的拷贝数(第8列)。
倍数变化显示在每种基因的第二个表中,其仅对有对照物的疾病组织进行了计算。没有对照物的所有标本在倍数变化列中显示空白。另外,倍数变化的数值是疾病标本和正常标本相比较的倍数变化。所以,任何正常标本的后面没有倍数变化数值。对于有成对肿瘤的患者(结肠,肺和乳腺),每种肿瘤与其特定的正常对照物相比较。如果不存在与患者相匹配的正常/疾病对,那么每种疾病标本要与同一组织类型的所有正常标本的平均值相比较。例如,不能应用来自提供阿尔茨海默(Alzheimer)脑的同一患者中的正常脑。在进行倍数变化的检测中,应用3个正常脑标本和4个阿尔茨海默脑标本。取3个正常标本的平均值,再将每个阿尔茨海默标本与该平均值进行比较。
缩写ALZ阿尔茨海默氏病CTCLONTECH(1020 East Meadow Circle Palo Alto,CA 94303-4230,USA)KC由GSK研究者制备的标本COPD慢性阻塞性肺病
Endo内皮细胞的VEGF血管内皮细胞生长因子bFGF碱性成纤维细胞生长因子BM骨髓Osteo成骨细胞OA骨关节炎RA类风湿性关节炎PBL外周血淋巴细胞PBMNC外周血单核细胞HIV人类免疫缺陷病毒HSV单纯疱疹病毒HPV人乳头瘤病毒基因名称sbg960509cbrecpt在正常和疾病标本中总体表达最低。在全脑,胚胎肝脏和子宫中有最高的正常表达。在2份肺肿瘤标本,一份乳腺肿瘤标本和一份正常乳腺标本中有最高的疾病表达。在4份结肠肿瘤的一份中下调提示其与结肠癌有关。在4份AD脑标本的2份中下调和在全脑中的高表达,提示其参与阿尔茨海默氏病。在3份COPD肺标本中都下调,和在4份哮喘肺标本中都下调,提示在COPD和哮喘中存在该基因。在3份心脏标本的2份中上调,提示其在非阻塞性和阻塞性DCM中的作用。由于Cts>35,上述模式很难解释。免疫细胞中有中度到低度的表达。在OA和RA滑膜中有中度表达。
基因名称sbg960509cbrecpt
基因名称sbg614126complfH在正常和疾病标本中,有中度到低度的总体表达。在肝脏和胚胎肝脏中有最高的正常表达。在全脑,卵巢和子宫中可见较低(但仍然是明显的)表达。在2份乳腺肿瘤样品,一份正常脑标本,一份正常肺标本,多份OA滑膜标本的一份中以及在HSV感染的MRC5细胞中有最高的疾病表达。在4份结肠肿瘤的一份中上调提示其在结肠肿瘤中的作用。在4份肺肿瘤的2份中下调,在4份乳腺肿瘤的1份中上调提示其在肺和乳腺癌中的作用。在全部3份COPD肺标本中下调和全部4份哮喘肺中下调提示其参与慢性阻塞性肺疾病和哮喘。在3份心脏标本的一份中上调提示其在DCM中的作用。在HSV中上调提示其作为潜在的宿主因子与单纯疱疹病毒有关。在免疫细胞,RA和OA滑膜骨和软骨有中度到低度的表达。
基因名称sbg614126complfH
基因名称sbg120703RNase在正常和疾病标本中有中度到低度的总体表达。在全脑和唾液腺中有最高水平的正常表达。在胚胎肝脏和胸腺中有中度表达。在2份正常的肺标本,一份肺肿瘤标本,正常软骨库和HSV感染的MRC5细胞中有最高的疾病表达。在4份结肠肿瘤的一份中上调提示其在结肠癌中的作用。在4份肺肿瘤标本的2份中下调提示其可能与肺癌有关。在4份乳腺肿瘤的2份中上调提示其参与乳腺癌。在所有3份COPD肺标本中都下调提示其参与COPD。在所有3份心脏标本中都上调提示在心脏疾病,如DCM和缺血中有该基因。在OA和RA的滑膜和OA的骨标本中高表达提示其可能参与骨关节炎和类风湿性关节炎。在HSV中上调提示该基因作为潜在的宿主因子与单纯疱疹病毒有关。在免疫细胞中有中度到低度的表达。
基因名称sbg120703RNase
基因名称sbg98530TS
在正常和疾病标本中有中度的总体表达。在全脑,子宫内膜和睾丸中有最高的正常表达。在正常心脏,骨骼肌和食管中有中度表达。在大部分胃肠道标本和女性生殖道标本中显示表达。在一份结肠肿瘤标本,所有3份心脏标本,和软骨细胞中有最高的疾病表达。数据突出显示肌肉特异性表达模时。在4份结肠肿瘤的一份中上调,在4份乳腺肿瘤的2份中上调提示其参与结肠肿癌和乳腺癌。在所有3份COPD标本中下调提示其在慢性阻塞性肺病中的作用。在HSV中下调提示其作为潜在的宿主因子与单纯疱疹病毒有关。在免疫细胞中有中度到低度的总体表达。在软骨细胞和OA和RA的滑膜中高表达提示其可能参与骨关节炎和类风湿性关节炎。
基因名称sbg98530TS
基因名称sbg563917RDP在正常和疾病标本中有中度到低度的总体表达。在睾丸,肝脏,气管和全脑中有最高的正常表达。在大多数胃肠道标本中显示良好表达。在T细胞,B细胞,中性粒细胞和嗜酸性粒细胞中有最高的疾病表达。在4份乳腺肿瘤的1份中上调提示其参与乳腺癌。在所有3份COPD肺中下调提示其参与慢性阻塞性肺病。在在缺血性心脏标本中下调提示在缺血性心脏疾病中涉及该基因。在VEGF和bFGF治疗的内皮细胞中下调提示其在血管生成的作用。在HSV中上调提示其作为潜在的宿主因子与单纯疱疹病毒有关。
基因名称sbg563917RDP
基因名称sbg618069LRR在正常和疾病标本中有低的总体表达。在全脑,胎脑,小脑和胸腺中有最高的正常表达。在1份结肠肿瘤标本,1份肺肿瘤标本,和未感染的PBL细胞中有最高的疾病表达。在4份结肠肿瘤的2份中下调提示其在结肠癌中的作用。在4份肺肿瘤的一份中上调和4份乳腺肿瘤的2份中上调提示其在肺癌和乳腺癌中的作用。在所有3份COPD肺标本中下调提示该基因在COPD中的作用。其在受到刺激的骨髓中上调。在HIV感染的细胞系中下调,和在免疫细胞中的中度表达提示其与HIV有关。在HSV中上调提示其作为潜在的宿主因子与单纯疱疹病毒有关。
基因名称sbg618069LRR
基因名称sbg934114Relaxin在正常和疾病标本中有低的总体表达。在睾丸,肝脏和全脑中有最高的正常表达。在3份正常肺标本,一份正常肿瘤标本中,HSV感染的MRC5细胞中,腺样增殖体(adenoid)中和T细胞中有最高的疾病表达。在2份正常肺标本中,1份肺肿瘤标本中,1份正常乳腺标本中,1份乳腺肿瘤标本中和未感染的PBL标本中有最高的疾病表达。在4份结肠肿瘤的1份中下调,在4份肺肿瘤的2份中下调提示其在结肠癌和肺癌中的作用。在所有3份COPD肺标本中下调,和4份哮喘肺标本的3份中上调提示COPD和哮喘涉及该基因。在3份心脏标本的2份中上调提示其在肺阻塞性和阻塞性DCM中的作用。在OA软骨库中下调,在RA和OA滑膜,OA骨,和软骨细胞中低表达提示其参与骨关节炎和类风湿性关节炎。在HIV感染的原代细胞系中下调提示其与HIV有关。在HSV中上调提示其作为潜在的宿主因子与单纯疱疹病毒有关。
基因名称sbg934114Relaxin
基因名称sbg99174LOX-like在正常和疾病标本中中度的总体表达。在全脑,肝脏,皮肤,脾脏,睾丸有最高的正常表达。在女性生殖道标本中和胃肠道标本中有相对好的表达。在一份正常肺标本中,一份哮喘肺标本中,中性粒细胞,嗜酸性粒细胞,2份RA滑膜标本中和一份OA骨标本中有最高的疾病表达。在4份肺肿瘤标本的1份中下调提示其可能参与肺癌。在4份乳腺肿瘤的2份中上调提示其参与乳腺癌。在4份AD脑的1份中下调和在脑中观察到的高表达提示其参与阿尔茨海默氏病。在3份COPD肺标本的2份中下调提示其参与慢性阻塞性肺病。在4份哮喘肺标本的1份中上调提示其在哮喘中的作用。在OA的软骨中下调和在OA和RA的滑膜中高表达提示其可能参与骨关节炎和类风湿性关节炎。在T细胞中证实高表达为其在RA/OA中的作用提供了补充的证据。在其它免疫细胞中为中度表达。
基因名称sbg99174LOX-like
基因名称sbg995002PIGR(Taqman)在正常和疾病标本中有极低的总体表达。在结肠和腮腺中有最高的正常表达。在一份肺肿瘤标本中和一份结肠肿瘤标本中有最高的疾病表达。在4份结肠肿瘤的1份中和4份肺肿瘤的1份中上调提示其在结肠癌和肺癌中的作用。在4份AD脑标本的3份中下调和在全脑中高表达提示其参与阿尔茨海默氏病。在所有3份COPD肺标本中下调提示该基因与COPD有关。在缺血性和非阻塞性DCM心脏标本中下调提示该基因在心血管疾病中的作用。其在受到刺激的骨髓标本中上调。在HSV中上调提示其作为潜在的宿主因子与单纯疱疹病毒有关。其在中性粒细胞和嗜酸性粒细胞中高表达。
基因名称sbg995002PIGR
基因名称sbg1033026C1q在正常和疾病标本中有低度到中度的总体表达。在皮下脂肪组织,皮下脂肪,全脑和心脏中有最高的正常表达。在3份心脏标本中有最高的疾病表达。在4份肺肿瘤标本的1份中下调和在4份乳腺肿瘤标本的2份中上调提示该基因在肺癌和乳腺癌中的作用。在4份AD脑标本的2份中上调提示其参与阿尔茨海默氏病。在所有3份心脏标本中上调提示参与心血管疾病,例如非阻塞性和阻塞性DCM和缺血。其在所有免疫细胞中低表达。在OA的滑膜和骨标本中和在RA的滑膜标本中为低度到中度表达。
基因名称sbg1033026C1q
基因名称sbg1003675Rnase失败基因名称sbg1015258PLM在正常和疾病标本中有低的总体表达。在子宫内膜,下丘脑,肝脏小肠和睾丸中有最高的正常表达。在一份乳腺正常/肿瘤对中,一份正常的脑标本中,二份阿尔茨海默氏病脑标本中,B细胞和HSV感染的MRC5细胞中有最高的疾病表达。在4份肺肿瘤标本的1份中下调,足以认定其在肺癌中的作用。在4份乳腺肿瘤标本的2份中上调提示其参与乳腺癌。在3份COPD标本的2份中下调和在4份哮喘肺标本的2份中下调提示其在慢性阻塞性肺病和哮喘中的作用。在阻塞性DCM心脏标本中上调提示其在心血管疾病中有潜在的作用。在受到刺激的骨髓标本中下调。在OA的软骨库中下调提示在骨关节炎中涉及该基因。在HSV感染的MRC5细胞中上调提示该基因可能是HSV中的宿主因子。在所有免疫细胞(除B细胞外)中低表达,在B细胞中中度表达。
基因名称sbg1015258PLM
基因名称sbg1003328IG(Taqman)中度的总体表达。在全脑,胎脑和小脑中有最高的正常表达,在结肠和乳腺中其表达水平略低。在结肠和肺肿瘤对,以及在正常和阿尔茨海默氏病脑中有最高的疾病表达。在4份乳腺肿瘤标本的2份中明显上调,在4份乳腺肿瘤标本的1份中轻微上调提示在乳腺癌中涉及该基因。
在所有3份COPD标本中下调可能提示与慢性阻塞性肺病有关。在4份哮喘标本的1份中下调提示其在哮喘中该基因的潜在作用。在HSV感染的MRC5细胞中下调提示该基因可能在HSV中起作用。在所有3份OA的滑膜标本中,所有3份RA滑膜标本中,所有2份OA骨标本中高表达,以及在T细胞和B细胞中确定的高表达提示在骨关节炎和类风湿性关节炎中涉及该基因。
基因名称sbg99174LOX-like
基因名称sbg1003328IG
基因名称sbg1020829SGLT在正常和疾病标本中有低的总体表达。在全脑,肾脏和胸腺中有最高的正常表达。在腺样增殖体,扁桃体,T细胞,B细胞和嗜酸性粒细胞中有最高的疾病表达。其有极高的免疫细胞特异性。在4份肺肿瘤标本的1份中下调和4份乳腺肿瘤标本的1份中上调提示其参与肺和乳腺肿瘤。在4份AD脑标本的3份中上调提示其参与阿尔茨海默氏病。在所有3份COPD标本中下调提示其在慢性阻塞性肺病中的作用。在受到刺激的骨髓中下调。在HSV感染的MRC5细胞中上调提示该基因可能是HSV中的宿主因子。在OA和RA标本中中度到高度的表达提示其在骨关节炎和类风湿性关节炎中的潜在作用。
基因名称sbg1020829SGLT
基因名称sbg1005450UDPGT其有低度到中度的总体表达。在子宫内膜,食管和脾脏有最高的正常表达,在小脑,下丘脑,直肠和子宫有较低的表达水平。在一份OA滑膜标本中有最高的疾病表达。在4份结肠肿瘤标本的1份中下调可足以作出有关结肠癌的疾病断言。在4份肺肿瘤标本的1份中上调提示该基因在肺癌中潜在的作用。在4份AD脑标本的2份中下调提示其参与阿尔茨海默氏病。在所有3份COPD肺标本中和所有4份哮喘肺标本中下调提示其参与慢性阻塞性肺病和哮喘。在HSV感染的MRC5细胞中上调提示该基因可能是HSV中的宿主因子。该基因在B细胞和树突细胞中中度表达。
基因名称sbg1005450UDPGT
基因名称sbg1002620Tia有中度总体表达。在全脑,子宫内膜,子宫肌层,胎盘和直肠中有最高的正常表达。在一份结肠正常/肿瘤对中,正常肺标本中,一份哮喘肺标本中,中性粒细胞,嗜酸性粒细胞,一份RA滑膜标本中有最高的疾病表达。在代表胃肠道的所有标本中的高水平表达提示该基因在IBS,IBD和Crohn’s病中的潜在作用。在3份COPD肺标本的1份中下调提示其参与慢性阻塞性肺病。在4份哮喘肺标本的1份中上调提示其在哮喘中的作用。在OA的滑膜和骨标本中和在RA滑膜标本中高表达。在软骨细胞中也高表达。在免疫细胞中有不同水平的表达,其中在中性粒细胞和嗜酸性粒细胞中有最高的表达,在树突细胞中有最低的表达。在B细胞和T细胞中以及OA的标本中确定的高表达表明,该基因与骨关节炎和类风湿性关节炎有关。
基因名称sbg1002620TIa
基因名称sbg1002620TIb中度到高度的总体表达。在全脑,子宫内膜,空肠,胎盘,胸腺和膀胱有最高的正常表达。在一份结肠正常/肿瘤对中,一份正常的肺标本中,一份哮喘肺标本中,中性粒细胞中和嗜酸性粒细胞中有最高的疾病表达。在所有胃肠道标本中的强表达提示该基因与IBS,IBD和Crohn’s病有关。在4份肺肿瘤标本的1份中下调可足以作出有关肺癌的疾病断言。在所有3份COPD肺标本中下调提示其参与慢性阻塞性肺病。在4份哮喘肺标本的1份中上调提示其在哮喘中的作用。在3份心脏标本的2份中上调该基因可能在非阻塞性和阻塞性扩张型心肌病中起作用。在RA和OA的滑膜标本中高表达,以及在软骨细胞和T细胞中高表达提示与骨关节炎和类风湿性关节炎有关。
基因名称sbg1002620TIb
基因名称sbg102200MCTa中度到低度的总体表达。在皮下脂肪组织,全脑,胎脑,小脑和胚胎肝脏中有最高的正常表达。在4份肺肿瘤标本的2份中,一份正传肺标本,一份正常乳腺标本,和CT肺标本中有最高的疾病表达。在4份乳腺癌标本的1份中下调提示该基因与乳腺癌有关。在所有3份COPD肺标本中下调提示该基因参与慢性阻塞性肺病。在OA和RA滑膜中,以及在PBL,腺样增殖体,扁桃体,T细胞,B细胞和软骨细胞中中度表达提示其参与骨关节炎和类风湿性关节炎。
基因名称sbg102200MCTa
基因名称sbg102200MCTb高度到中度的总体表达。在全脑,肝脏,胚胎肝脏和胸腺有最高的正常表达。在一份结肠正常/肿瘤对,一份肺正常正常/肿瘤对,一份哮喘肺标本,树突细胞,未感染HIV和感染的HIV的PBL细胞中有最高的疾病表达。在4份乳腺肿瘤标本的2份中上调可足以作出有关乳腺癌的疾病断言。在4份AD脑标本的1份中上调提示其在阿尔茨海默氏病中潜在的作用。在所有3份COPD肺标本中下调提示其参与慢性阻塞性肺病。在4份哮喘肺标本的1份中上调提示该基因在肺癌中潜在的作用。在所有免疫细胞中高表达。在OA和RA滑膜标本中,OA骨标本中,和软骨细胞中也有高度到中度的表达,这提示其参与骨关节炎和类风湿性关节炎。
基因名称sbg102200MCTb
基因名称sbg1020380LYG失败基因名称sbg1007026SGLT良好到中度的总体表达。在全脑,小脑,下丘脑,空肠,胚胎肝脏,直肠和子宫中可见最高的正常表达。该基因在代表中枢神经系统,女性生殖器官和胃肠道的标本中显示系统特异性表达。在疾病标本中观察到的表达证实了在正常标本中观察到的表达,其中在正常和阿尔茨海默氏病脑标本中观察到最高水平的表达。在4份结肠肿瘤标本的1份中上调和在4份乳腺肿瘤标本的2份中上调,以及在4份肺肿瘤的一份中下调提示该基因在结肠癌和乳腺癌中有潜在作用。在4份阿尔茨海默氏病标本的2份中下调提示其参与阿尔茨海默氏病。在所有3份COPD标本中下调和在4份哮喘肺标本的2份中上调提示该基因在慢性阻塞性肺病中的潜在作用。在VEGF治疗的内皮细胞系中上调提示该基因在血管生成中可能的作用。在受到刺激的骨髓标本中下调。在RA和OA的滑膜标本中,OA的骨标本中,和软骨细胞中的高表达,以及在T细胞,B细胞,中性粒细胞和嗜酸性粒细胞中确定的高表达提示,该基因与骨关节炎和类风湿性关节炎有关。
基因名称sbg1007026SGLT
基因名称sbg1012732GLUT高度到中度的总体表达。该基因在所有参与分析的正常标本中的表达是相对普遍的,其中在全脑,胎脑,小脑,肾脏,胚胎肝脏和胎盘中表达水平最高。该基因在疾病标本中也有相当普遍的表达。在所有3份COPD标本中下调提示该基因在慢性阻塞性肺病中潜在的作用。在所有3份疾病心脏的标本中上调提示其参与心血管疾病,如非阻塞性和阻塞性DCM和缺血。在HSV感染的MRC5细胞中下调提示该基因在HSV中可能起作用。在分化的成骨细胞中上调。在RA和OA的滑膜标本中,在OA的骨标本中和软骨细胞中的高表达,和在T细胞,B细胞,树突细胞,中性粒细胞和嗜酸性粒细胞中确定的高表达提示,该基因与骨关节炎和类风湿性关节炎有关。
基因名称sbg1012732GLUT
基因名称sbg1012732GLUTb与sbg1012732GLUT相同。
基因名称sbg1018172CSP中度到低度的总体表达。在全脑,肾脏,甲状腺和子宫可见最高的正常表达。该基因在代表女性生殖系统的所有标本中表达。在许多正常/肿瘤肺标本中和哮喘肺标本中可见最高的疾病表达。在4份肺肿瘤标本的2份中下调,4份乳腺肿瘤标本的2份中上调提示其参与肺癌和乳腺癌。在所有3份COPD标本中下调提示该基因在慢性阻塞性肺病中潜在的作用。在4份哮喘肺标本的2份中上调提示其参与哮喘。在3份疾病心脏标本的1份中上调提示其参与心血管疾病,如阻塞性DCM。在OA的软骨库中下调和在免疫细胞(特别是T细胞和B细胞)中确定的低表达提示,该基因与骨关节炎和类风湿性关节炎有关。在HSV感染的MRC5细胞中的上调提示该基因可能是HSV中的宿主因子。
基因名称sbg1018172CSP
基因名称sbg1004570ERGIC中度到低度的总体表达。该基因在所有参与分析的正常标本中表达相当普遍,其中在全脑,下丘脑,胰腺和胰头有最高水平的表达。该表达模式提示该基因可能参与糖尿病和其它代谢性疾病。在结肠,乳腺和肺的正常/肿瘤对以及阿尔茨海默氏病脑标本,T细胞,B细胞,树突细胞和嗜酸性粒细胞中可见最高的疾病表达。在4份乳腺肿瘤标本的2份中上调提示该基因在乳腺癌中的作用。在4份阿尔茨海默氏病脑标本的2份中上调提示其参与阿尔茨海默氏病。在所有3份COPD标本中和所有4份哮喘肺标本中下调提示该基因在慢性阻塞性肺病和哮喘中潜在的作用。在受到刺激的骨髓中上调。
基因名称sbg1004570ERGIC
基因名称sbg1016995IGBrecpt中度到低度的总体表达。在全脑,肺中可见最高的正常表达,在子宫内膜,回肠,直肠和皮肤有略低水平的表达。在皮肤中的高水平表达可能提示该基因在牛皮癣和狼疮中可能的作用。在疾病板上的标本中的表达模式提示该基因对腺样增殖体和扁桃体的极高特异性。在4份肺肿瘤标本的2份中下调和在4份乳腺肿瘤标本的2份中上调提示其参与肺癌和乳腺癌。在所有3份COPD标本中下调提示该基因在慢性阻塞性肺病中的潜在作用。在受到刺激的骨髓中上调。在分化的成骨细胞中下调。在HIV感染的PBL细胞中上调提示该基因可能是HIV中的宿主因子。
基因名称sbg1016995IGBrecpt
基因名称sbg1151bSREC在正常和疾病标本中有最高的总体表达。其表达相当普遍,但在脂肪细胞,脂肪,全脑,胎脑和子宫内膜中最高的正常表达。在一份结肠肿瘤标本中,一份正常肺标本中,软骨细胞中和未感染的MRC5细胞中有最高的疾病表达。在阿尔茨海默氏病患者的脑中没有明显的变化。在4份肺肿瘤的1份中下调提示其可能参与肺癌。在4份乳腺肿瘤标本的1份中上调可足以断定其在乳腺癌中的作用。在4份哮喘肺的1份中上调提示其在哮喘中的作用。在HSV中下调提示其作为潜在的宿主因子与单纯疱疹病毒有关。在免疫细胞中高表达。在来自OA患者的软骨和骨标本中高表达以及在软骨细胞中的高表达提示其可能参与骨关节炎和类风湿性关节炎。另外,在免疫细胞中(尤其是B细胞和T细胞中)确定的表达为其在RA/OA中的作用提供了附加的证据。
基因名称sbg1151bSREC
基因名称sbg1399854ANK低度总体表达。在全脑,胎脑和肝脏可见最高的正常表达。在代表女性生殖系统的所有标本中可见良好的表达水平。在正常和阿尔茨海默氏病脑标本中以及在树突细胞中可见最高的疾病表达。在4份结肠肿瘤标本的2份中上调和在4份乳腺肿瘤标本的2份中上调,以及在4份肺肿瘤标本的2份中下调提示该基因与结肠癌,乳腺癌和肺癌有关。在所有3份COPD标本中下调和在4份哮喘标本的2份中下调提示该基因在慢性阻塞性肺病和哮喘中的潜在作用。在OA的软骨标本中下调和在正常软骨细胞和许多免疫细胞中的确定的低表达提示其参与骨关节炎。在HSV感染的HRC5细胞中上调提示该基因可能是HSV中的宿主因子。
基因名称sbg1399854ANK
表V.基于特异性组织中mRNA表达的其它疾病
序列表<110>史密斯克莱恩·比彻姆公司(SMITHKLINE BEECHAM CORPORATION)史密斯克莱·比奇曼生物公司(SMITHKLINE BEECHAM p.l.c.)葛兰素集团有限公司(GLAXO GROUP,LIMITED)<120>新型化合物<130>GP50034<140>TO BE ASSIGNED<141>2001-09-13<150>60/232,463<151>2000-09-13<150>60/232,455<151>2000-09-13<150>60/237,293<151>2000-10-02<150>60/246,269<151>2000-11-07<150>60/252,049<151>2000-11-20<160>88<170>FastSEQ for Windows Version 4.0<210>1<211>1707<212>DNA<213>人(Homo sapiens)<400>1atgaaggaag cagagatgga cggtgaggca gtccgcttct gcacagataa ccagtgtgtc 60tccctgcacc cccaagaggt ggactctgtg gcaatggctc ctgcagcccc caagataccg 120aggctcgttc aggctacccc ggcatttatg gctgtgacct tggtcttctc tcttgtgact 180ctctttgtag tgggtaagcc cccagttcaa cagcagacaa gacctgttcc gaagcctgtg 240caagccgtaa ttctgggaga caacattact gggcatttac cttttgaacc caacaatcat 300caccactttg gcagggaggc agaaatgcga gagcttatcc agacatttaa aggccacatg 360gagaattcca gtgcctgggt agtagaaatc cagatgttga agtgcagagt ggacaatgtc 420aattcgcagc tccaggtgct cggtgatcat ctgggaaaca ccaatgctga catccagatg 480gtaaaaggag ttctaaagga tgccactaca ttgagtttgc agacacagat gttaaggagt 540tccctggagg gaaccaatgc tgagatccag aggctcaagg aagaccttga aaaggcagat 600gctttaactt tccagacgct gaatttctta aaaagcagtt tagaaaacac cagcattgag 660ctccacgtgc taagcagagg cttagaaaat gcaaactctg aaattcagat gttgaatgcc 720agagccaatg ctgagatcca gggactaaag gaaaatttgc agaacacaaa tgctttaaac 780tcccagaccc aggcctttat aaaaagcagt tttgacaaca ctagtgctga gatccagttc 840ttaagaggtc atttggaaag agctggtgat gaaattcacg tgttaaaaag ggatttgaaa 900atggtcacag cccagaccca aaaagcaaat ggccgtctgg accagacaga tactcagatt 960caggtattca agtcagagat ggaaaatgtg aataccttaa atgcccagat tcaggtctta1020aatggtcata tgaaaaatgc cagcagagag atacagaccc taaaacaagg aatgaagaat1080gcttcagcct taacttccca gacccagatg ttagacagca atctgcagaa ggccagtgcc1140gagatccaga ggttaagagg ggatctagag aacaccaaag ctctaaccat ggaaatccag1200caggagcaga gtcgcctgaa gaccctccat gtggtcatta cttcacagga acagctacaa1260agaacccaaa gtcagcttct ccagatggtc ctgcaaggct ggaagttcaa tggtggaagc1320ttatattatt tttctagtgt caagaagtct tggcatgagg ctgagcagtt ctgcgtgtcc1380cagggagccc atctggcatc tgtggcctcc aaggaggagc aggcatttct ggtagagttc1440acaagtaaag tgtactactg gatcggtctc actgacaggg gcacagaggg ctcctggcgc1500tggacagatg ggacaccatt caacgccgcc cagaacaaag cccctgttgt cttcgggttt1560tgggaaaaga atcagtctga caactggcgg cacaagaatg ggcagactga agactgtgtc1620caaattcagc agaagtggaa tgacatgacc tgtgacaccc cctatcagtg ggtgtgcaag1680aagcccatgg gccagggtgt ggcctga 1707<210>2<211>1095<212>DNA<213>人(Homo sapiens)<400>2atgtcgagac aaggaaaatt attttctgct tttggagtgg gttgttgtgt aacggcaggc 60ttgccaaagg acgataacac tcctagcacc attgcggatg tgcacaatgg ttatacgatg 120aatgttgtag agcaagttct aaaggatagt tttgtgttat ttttcccagg aacactttgt 180gattttccaa aaatacacca tggatttctg tatgatgaag aagattataa ccctttttcc 240caagttccta caggggaagt tttctattac tcctgtgaat ataattttgt gtctccttca 300aaatcctttt ggactcgcat aacatgcaca gaagaaggat ggtcaccaac accgaagtgt 360ctcagaatgt gttcctttcc ttttgtgaaa aatggtcatt ctgaatcttc aggactaata 420catctggaag gtgatactgt acaaattatt tgcaacacag gatacagcct tcaaaacaat 480gagaaaaaca tttcgtgtgt agaacggggc tggtccactc ctcccatatg cagcttcact 540atgaaaacat gtggatacat acctgaactc gagtacggtt atgttcagcc gtctgtccct 600ccctatcaac atggagtttc agtcgaggtg aattgcagaa atgaatatgc aatgattgga 660aataacatga ttacctgtat taatggaata tggacagagc ttcctatgtg tgttgagtct 720actgcatatt gtgggccccc tccatctatt aacaatggag ataccacctc attcccatta 780tcagtatatc ctccagggtc aacagtgacg taccgttgcc agtccttcta taaactccag 840ggctctgtaa ctgtaacatg cagaaataaa cagtggtcag aaccaccaag atgcctagat 900ccatgtgtgg tatctgaaga aaacatgaac aaaaataaca tacagttaaa atggagaaac 960gatggaaaac tctatgcaaa aacaggggat gctgttgaat tccagtgtaa attcccacat1020aaagcgatga tatcatcacc accatttcga gcaatctgtc aggaagggaa atttgaatat1080cctatatgtg aatga 1095<210>3<211>984<212>DNA<213>人(Homo sa piens)<400>3atgttgctct tattcagtgt aatcctaatc tcatgggtat ccactgttgg gggagaagga 60acactttgtg attttccaaa aatacaccat ggatttctgt atgatgaaga agattataac 120cctttttccc aagttcctac aggggaagtt ttctattact cctgtgaata taattttgtg 180tctccttcaa aatccttttg gactcgcata acatgcacag aagaaggatg gtcaccaaca 240ccgaagtgtc tcagaatgtg ttcctttcct tttgtgaaaa atggtcattc tgaatcttca 300ggactaatac atctggaagg tgatactgta caaattattt gcaacacagg atacagcctt 360caaaacaatg agaaaaacat ttcgtgtgta gaacggggct ggtccactcc tcccatatgc 420agcttcacta tgaaaacatg tggatacata cctgaactcg agtacggtta tgttcagccg 480tctgtccctc cctatcaaca tggagtttca gtcgaggtga attgcagaaa tgaatatgca 540atgattggaa ataacatgat tacctgtatt aatggaatat ggacagagct tcctatgtgt 600gttgagtcta ctgcatattg tgggccccct ccatctatta acaatggaga taccacctca 660ttcccattat cagtatatcc tccagggtca acagtgacgt accgttgcca gtccttctat 720aaactccagg gctctgtaac tgtaacatgc agaaataaac agtggtcaga accaccaaga 780tgcctagatc catgtgtggt atctgaagaa aacatgaaca aaaataacat acagttaaaa 840tggagaaacg atggaaaact ctatgcaaaa acaggggatg ctgttgaatt ccagtgtaaa 900ttcccacata aagcgatgat atcatcacca ccatttcgag caatctgtca ggaagggaaa 960tttgaatatc ctatatgtga atga984<210>4<211>465<212>DNA<213>人(Homo sapiens)<400>4atggcaccgg ccagagcagg atgctgcccc ctgctgctgc tgcttctggg gctgtgggtg 60gcagaggtcc tagtcagagc caagcccaag gacatgacat catctcagtg gtttaaaact 120cagcatgtgc agcccagccc tcaagcatgc aactcagcca tgagcatcat caataagtac 180acagaacggt gcaaagacct caacaccttc ctgcacgagc ccttctccag tgtggccatc 240acctgccaga cccccaacat agcctgcaag aatagctgta aaaactgcca ccagagccac 300gggcccatgt ccctgaccat gggtgagctc acctcaggga agtacccaaa ctgcaggtac 360aaagagaagc acctgaacac accttacata gtggcctgtg accctccaca acagggtgac 420ccagggtacc cacttgttcc tgtgcacttg gataaagttg tctaa 465<210>5<211>1509<212>DNA<213>人(Homo sapiens)<400>5atgcgccagc tgggagggtc tctccgcccc ccgcgcgcgg cccacggggc cgagcctctc 60cccagtgcgc tggggccctg cgctgggggt gaccgggacc tgggtcgggg aacccccgga 120tgggagccca ggcgcgccag ggtccccatc cacgagcagg tcgacccccc gcgagagggg 180ccccacctct tccagaacct cctgctcttc ctgtgggccc tgctgaactg tggtttgggg 240gtcagtgctc agggtccggg cgagtggacc ccgtgggtgt cctggacccg ctgctccagc 300tcctgcgggc gtggcgtctc tgtgcgcagc cggcgctgcc tccggcttcc tggggaagaa 360ccgtgctggg gagactccca tgagtaccgc ctctgccagt tgccagactg ccccccaggg 420gctgtgccct tccgagacct acagtgtgcc ctgtacaatg gccgccctgt cctgggcacc 480cagaagacct accagtgggt gcccttccat ggggcgccca accagtgcga cctcaactgc 540ctggctgagg ggcacgcctt ctaccacagc ttcggccgcg tcctggacgg caccgcctgc 600agcccgggtg cccagggggt ctgcgtggct ggccgctgcc ttagcgccgg ctgtgatggg 660ttgttgggct cgggtgccct cgaggaccgc tgtggccgct gcggaggcgc caacgactcg 720tgccttttcg tgcagcgcgt gtttcgtgac gccggtgcct tcgctgggta ctggaacgtg 780accctgatcc ccgagggcgc cagacacatc cgcgtggaac acaggagccg caaccacctg 840ggtatcctag gatcactgat ggggggcgat gggcgctacg tgcttaatgg gcactgggtg 900gtcagcccac cagggaccta cgaggcggcc ggcacgcatg tggtctacac ccgagacaca 960gggccccagg agacattgca agcagccggg cccacctccc atgacctgct cctacaggtc1020ctcctgcagg agcccaaccc tggcatcgag tttgagttct ggctccctcg ggagcgctac1080agccccttcc aggctcgtgt gcaggccctg ggctggcccc tgaggcagcc tcagccccgg1140ggggtggagc ctcagccccc cgcagcccct gctgtcaccc ctgcacagac cccaacgctg1200gccccagtgt tccaggcccg agtgctgggc caccaccacc aggcccagga gacccgctat1260gaggtgcgca tccagctcgt ctacaagaac cgctcgccac tgcgggcacg cgagtacgtg1320tgggcgccag gccactgccc ctgcccgatg ctggcacccc accgggacta cctgatggct1380gtccagcgtc ttgtcagccc cgacggcaca caggaccagc tgctgctgcc ccacgccggc1440tacgcccggc cctggagccc tgcggaggac agccgcatac gcctgactgc ccggcgctgt1500cctggctga1509<210>6<211>1356<212>DNA<213>人(Homo sapiens)<400>6atggactcgg cccctctgtt ccccaggccc cacctcttcc agaacctcct gctcttcctg 60tgggccctgc tgaactgtgg tttgggggtc agtgctcagg gtccgggcga gtggaccccg 120tgggtgtcct ggacccgctg ctccagctcc tgcgggcgtg gcgtctctgt gcgcagccgg 180cgctgcctcc ggcttcctgg ggaagaaccg tgctggggag actcccatga gtaccgcctc 240tgccagttgc cagactgccc cccaggggct gtgcccttcc gagacctaca gtgtgccctg 300tacaatggcc gccctgtcct gggcacccag aagacctacc agtgggtgcc cttccatggg 360gcgcccaacc agtgcgacct caactgcctg gctgaggggc acgccttcta ccacagcttc 420ggccgcgtcc tggacggcac cgcctgcagc ccgggtgccc agggggtctg cgtggctggc 480cgctgcctta gcgccggctg tgatgggttg ttgggctcgg gtgccctcga ggaccgctgt 540ggccgctgcg gaggcgccaa cgactcgtgc cttttcgtgc agcgcgtgtt tcgtgacgcc 600ggtgccttcg ctgggtactg gaacgtgacc ctgatccccg agggcgccag acacatccgc 660gtggaacaca ggagccgcaa ccacctgggt atcctaggat cactgatggg gggcgatggg 720cgctacgtgc ttaatgggca ctgggtggtc agcccaccag ggacctacga ggcggccggc 780acgcatgtgg tctacacccg agacacaggg ccccaggaga cattgcaagc agccgggccc 840acctcccatg acctgctcct acaggtcctc ctgcaggagc ccaaccctgg catcgagttt 900gagttctggc tccctcggga gcgctacagc cccttccagg ctcgtgtgca ggccctgggc 960tggcccctga ggcagcctca gccccggggg gtggagcctc agccccccgc agcccctgct 1020gtcacccctg cacagacccc aacgctggcc ccagtgttcc aggcccgagt gctgggccac 1080caccaccagg cccaggagac ccgctatgag gtgcgcatcc agctcgtcta caagaaccgc 1140tcgccactgc gggcacgcga gtacgtgtgg gcgccaggcc actgcccctg cccgatgctg 1200gcaccccacc gggactacct gatggctgtc cagcgtcttg tcagccccga cggcacacag 1260gaccagctgc tgctgcccca cgccggctac gcccggccct ggagccctgc ggaggacagc 1320cgcatacgcc tgactgcccg gcgctgtcct ggctga 1356<210>7<211>1296<212>DNA<213>人(Homo sapiens)<400>7atgatccgga ccccattgtc ggcctctgcc catcgcctgc tcctcccagg ctcccgcggc 60cgacccccgc gcaacatgca gcccacgggc cgcgagggtt cccgcgcgct cagccggcgg 120tatctgcggc gtctgctgct cctgctactg ctgctgctgc tgcggcagcc cgtaacccgc 180gcggagacca cgccgggcgc ccccagagcc ctctccacgc tgggctcccc cagcctcttc 240accacgccgg gtgtccccag cgccctcact accccaggcc tcactacgcc aggcaccccc 300aaaaccctgg accttcgggg tcgcgcgcag gccctgatgc ggagtttccc actcgtggac 360gggtatgtag gtctgaacag ctctcaaaag ctggcctgcc tcattggcgt ggagggtggt 420cactcactgg acagcagcct ctctgtgctg cgcagtttct atgtgctggg ggtgcgctac 480ctgacactta ccttcacctg cagtacacca tgggcagaga gttccaccaa gttcagacac 540cacatgtaca ccaacgtcag cggattgaca agctttggtg agaaagtagt agaggagttg 600aaccgcctgg gcatgatgat agatttgtcc tatgcatcgg acaccttgat aagaagggtc 660ctggaagtgt ctcaggctcc tgtgatcttc tcccactcag ctgccagagc tgtgtgtgac 720aatttgttga atgttcccga tgatatcctg cagcttctga agaagaacgg tggcatcgtg 780atggtgacac tgtccatggg ggtgctgcag tgcaacctgc ttgctaacgt gtccactgtg 840gcagatgatt cgaatcgatg ctcggtaccc gtcattggat ctgagttcat cgggattggt 900ggaaattatg acgggactgg ccggttccct caggggctgg aggatgtgtc cacataccca 960gtcctgatag aggagttgct gagtcgtagc tggagcgagg aagagcttca aggtgtcctt1020cgtggaaacc tgctgcgggt cttcagacaa gtggaaaagg tgagagagga gagcagggcg1080cagagccccg tggaggctga gtttccatat gggcaactga gcacatcctg ccactcccac1140ctcgtgcctc agaatggaca ccaggctact catctggagg tgaccaagca gccaaccaat1200cgggtcccct ggaggtcctc aaatgcctcc ccataccttg ttccaggcct tgtggctgct1260gccaccatcc caaccttcac ccagtggctc tgctga 1296<210>8<211>1443<212>DNA<213>人(Homo sapiens)<400>8atgcagccct ccggcctcga gggtcccggc acgtttggtc ggtggcctct gctgagtctg 60ctgctcctgc tgctgctgct ccagcctgta acctgtgcct acaccacgcc aggccccccc 120agagccctca ccacgctggg cgcccccaga gcccacacca tgccgggcac ctacgctccc 180tcgaccacac tcagtagtcc cagcacccag ggcctgcaag agcaggcacg ggccctgatg 240cgggacttcc cgctcgtgga cggccacaac gacctgcccc tggtcctaag gcaggtttac 300cagaaagggc tacaggatgt taacctgcgc aatttcagct acggccagac cagcctggac 360aggcttagag atggcctcgt gggcgcccag ttctggtcag cctatgtgcc atgccagacc 420caggaccggg atgccctgcg cctcaccctg gagcagattg acctcatacg ccgcatgtgt 480gcctcctatt ctgagctgga gcttgtgacc tcggctaaag gtctgaacag ctctcaaaag 540ctggcctgcc tcattggcgt ggagggtggt cactcactgg acagcagcct ctctgtgctg 600cgcagtttct atgtgctggg ggtgcgctac ctgacactta ccttcacctg cagtacacca 660tgggcagaga gttccaccaa gttcagacac cacatgtaca ccaacgtcag cggattgaca 720agctttggtg agaaagtagt agaggagttg aaccgcctgg gcatgatgat agatttgtcc 780tatgcatcgg acaccttgat aagaagggtc ctggaagtgt ctcaggctcc tgtgatcttc 840tcccactcag ctgccagagc tgtgtgtgac aatttgttga atgttcccga tgatatcctg 900cagcttctga agaagaacgg tggcatcgtg atggtgacac tgtccatggg ggtgctgcag 960tgcaacctgc ttgctaacgt gtccactgtg gcagatcact ttgaccacat cagggcagtc1020attggatctg agttcatcgg gattggtgga aattatgacg ggactggccg gttccctcag1080gggctggagg atgtgtccac atacccagtc ctgatagagg agttgctgag tcgtagctgg1140agcgaggaag agcttcaagg tgtccttcgt ggaaacctgc tgcgggtctt cagacaagtg1200gaaaaggtga gagaggagag cagggcgcag agccccgtgg aggctgagtt tccatatggg1260caactgagca catcctgcca ctcccacctc gtgcctcaga atggacacca ggctactcat1320ctggaggtga ccaagcagcc aaccaatcgg gtcccctgga ggtcctcaaa tgcctcccca1380taccttgttc caggccttgt ggctgctgcc accatcccaa ccttcaccca gtggctctgc1440tga 1443<210>9<211>1116<212>DNA<213>人(Homo sapiens)<400>9atggatgcag ccacagctcc aaagcaagcc tggcccccat ggcccccgct ccttttcctc 60ctcctcctac ctggagggag cggtggcagc tgccctgctg tgtgtgactg cacctcccag 120ccccaggctg tgctctgtgg ccacaggcaa ctggaggctg tacctggagg actcccactg 180gacactgagc tcctggacct gagtgggaac cgcctcccga aggctcagcc cctggtgcgg 240ctccaggagc tacgcctgtc aggggcatgc ctcacctcca ttgctgccca tgccttccat 300ggcttgactg ccttccacct cctggatgtg gcagataacg cccttcagac actagaggaa 360acagctttcc cttctccaga caaactggtc accttgaggc tgtctggcaa ccccctaacc 420tgtgactgcc gcctcctctg gctgctccgg ctccgccacc tggactttgg catgtccccc 480cctgcctgtg ctggccccca tcatgtccag gggaagagcc tgaaggagtt ttcagacatc 540ctgcctccag ggcacttcac ctgcaaacca gccctgatcc gaaagtcggg gcctcgatgg 600gtcattgcag aggagggcgg gcatgcggtt ttctcctgct ctggagatgg agacccagcc 660cccactgtct cctggatgag gcctcatggg gcttggctgg gcagggctgg gagagtaagg 720gtcctagagg atgggacact ggagatccgc tcagtgcagc tacgggacag aggggcctat 780gtctgtgtgg ttagcaatgt cgctgggaat gactccctga ggacctggct ggaagtcatc 840caggtggaac caccaaacgg cacactttct gaccccaaca tcaccgtgcc agggatccca 900gggccttttt ttctggatag cagaggtgtg gccatggtgc tggcagtcgg cttcctcccc 960ttcctcacct cagtgaccct ctgctttggc ctgattgccc tttggagcaa gggcaaaggt1020cgggtcaaac atcacatgac ctttgacttt gtggcacctc ggccctctgg ggataaaaac1080tctgggggta accgggtcac tgccaagctc ttctga 1116<210>10<211>1779<212>DNA<213>人(Homo sapiens)<400>10atggatgcag ccacagctcc aaagcaagcc tggcccccat ggcccccgct ccttttcctc 60ctcctcctac ctggagggag cggtggcagc tgccctgctg tgtgtgactg cacctcccag 120ccccaggctg tgctctgtgg ccacaggcaa ctggaggctg tacctggagg actcccactg 180gacactgagc tcctggacct gagtgggaac cgcctgtggg ggctccagca gggaatgctc 240tcccgcctga gcctgctcca ggaattggac ctcagctaca accagctctc aacccttgag 300cctggggcct tccatggcct acaaagccta ctcaccctga ggctgcaggg caatcggctc 360agaatcatgg ggcctggggt cttctcaggc ctctctgctc tgaccctgct ggacctccgc 420ctcaaccaga ttgttctctt cctagatgga gcttttgggg agctaggcag cctccagaag 480ctggaggttg gggacaacca cctggtattt gtggctccgg gggcctttgc agggctagcc 540aagttgagca ccctcaccct ggagcgctgc aacctcagca cagtgcctgg cctagccctt 600gcccgtctcc cggcactagt ggccctaagg cttagagaac tggatattgg gaggctgcca 660gctggggccc tgcgggggct ggggcagctc aaggagctgg agatccacct ctggccatct 720ctggaggctc tggaccctgg gagcctggtt gggctcaatc tcagcagcct ggccatcact 780cgctgcaatc tgagctcggt gcccttccaa gcactgtacc acctcagctt cctcagggtc 840ctggatctgt cccagaatcc catctcagcc atcccagccc gaaggctcag ccccctggtg 900cggctccagg agctacgcct gtcaggggca tgcctcacct ccattgctgc ccatgccttc 960catggcttga ctgccttcca cctcctggat gtggcagata acgcccttca gacactagag1020gaaacagctt tcccttctcc agacaaactg gtcaccttga ggctgtctgg caacccccta1080acctgtgact gccgcctcct ctggctgctc cggctccgcc acctggactt tggcatgtcc1140ccccctgcct gtgctggccc ccatcatgtc caggggaaga gcctgaagga gttttcagac1200atcctgcctc cagggcactt cacctgcaaa ccagccctga tccgaaagtc ggggcctcga1260tgggtcattg cagaggaggg cgggcatgcg gttttctcct gctctggaga tggagaccca1320gcccccactg tctcctggat gaggcctcat ggggcttggc tgggcagggc tgggagagta1380agggtcctag aggatgggac actggagatc cgctcagtgc agctacggga cagaggggcc1440tatgtctgtg tggttagcaa tgtcgctggg aatgactccc tgaggacctg gctggaagtc1500atccaggtgg aaccaccaaa cggcacactt tctgacccca acatcaccgt gccagggatc1560ccagggcctt tttttctgga tagcagaggt gtggccatgg tgctggcagt cggcttcctc1620cccttcctca cctcagtgac cctctgcttt ggcctgattg ccctttggag caagggcaaa1680ggtcgggtca aacatcacat gacctttgac tttgtggcac ctcggccctc tggggataaa1740aactctgggg gtaaccgggt cactgccaag ctcttctga 1779<210>11<211>429<212>DNA<213>人(Homo sapiens)<400>11atggccaggt acatgctgct gctgctcctg gcggtatggg tgctgaccgg ggagctgtgg 60ccgggagctg aggcccgggc agcgccttac ggggtcaggc tttgcggccg agaattcatc 120cgagcagtca tcttcacctg cgggggctcc cggtggagac gatcagacat cctggcccac 180gaggctatgg gagatacctt cccggatgca gatgctgatg aagacagtct ggcaggcgag 240ctggatgagg ccatggggtc cagcgagtgg ctggccctga ccaagtcacc ccaggccttt 300tacagggggc gacccagctg gcaaggaacc cctggggttc ttcggggcag ccgagatgtc 360ctggctggcc tttccagcag ctgctgcaag tgggggtgta gcaaaagtga aatcagtagc 420ctttgctag 429<210>12<211>692<212>DNA<213>人(Homo sapiens)<400>12atgtctgaag aagtgaccta cgcgacactc acatttcagg attctgctgg agcaaggaat 60aaccgagatg gaaataacct aagaaaaaga gggcatccag ctccatctcc catttggcgt 120catgctgctc tgggtctggt aactctttgc ctgatgttgc tgattgggct ggtgacgttg 180gggatgatgt ttttgcagat atctaatgac attaactcag attcagagaa attgagtcaa 240cttcagaaaa ccatccaaca gcagcaggat aacttatccc agcaactggg caactccaac 300aacttgtcca tggaggagga atttctcaag tcacagatct ccagtctact gaagaggcag 360gaacaaatgg ccatcaaact gtgccaagag ctaatcattc atacttcaga ccacagatgt 420aatccatgtc ctaagatgtg gcaatggtac caaaatagtt gctactattt tacaacaaat 480gaggagaaaa cctgggctaa cagtagaaag gactgcatag acaagaactc caccctagtg 540aagatagaca gtttggaaga aaaggatttt cttatgtcac agccattact catgttttcg 600ttcttttggc tgggattatc atgggactcc tctggcagaa gttggttctg ggaagatggc 660tctgttccct ctccatcctt gtacgtctct aa 692<210>13<211>585<212>DNA<213>人(Homo sapiens)<400>13atgtggctgt ccccagctct gctgcttctc atcctcccag gttactccat tgccgctaaa 60atcactggtc caacaacagt gaatggctcg gagcagggct cattgactgt gcagtgtgct 120tatggctcag gctgggagac ctacttgaag tggcggtgtc aaggagctga ttggaattac 180tgtaacatcc ttgttaaaac aaatggatca gagcaggagg taaagaagaa tcgagtttcc 240atcagggaca atcagaaaaa ccacatgttc accgtgacca tggagaatct caaaagagat 300gatgctgaca gttattggtg tgggactgag agacctggaa ttgatcttgg ggtcaaagtt 360caagtgacca ttaacccagg cacacaaact gcagtctcag aatggacaac cacaacagca 420agcctggctt tcacagctgc agccacccag aagaccagca gccccctcac caggtccccg 480ctcaagagca cccacttcct gttcctgttc ctcctggagc tgcctctgct cctgagcatg 540ctggggaccg tcctctgggt gaacagacca caaagaaggt cttga 585<210>14<211>1002<212>DNA<213>人(Homo sapiens)<400>14atgaggatct ggtggcttct gcttgccatt gaaatctgca cagggaacat aaactcacag 60gacacctgca ggcaagggca ccctggaatc cctgggaacc ccggtcacaa tggtctgcct 120ggaagagatg gacgagacgg agcgaagggt gacaaaggcg atgcaggaga accaggacgt 180cctggcagcc cggggaagga tgggacgagt ggagagaagg gagaacgagg agcagatgga 240aaagttgaag caaaaggcat caaaggtgat caaggctcaa gaggatcccc aggaaaacat 300ggccccaagg ggcttgcagg gcccatggga gagaagggcc tccgaggaga gactgggcct 360caggggcaga aggggaataa gggtgacgtg ggtcccactg gtcctgaggg gccaaggggc 420aacattgggc ctttgggccc aactggttta ccgggcccca tgggccctat tggaaagcct 480ggtcccaaag gagaagctgg acccacgggg ccccagggtg agccaggagt ccggggaata 540agaggctgga aaggagatcg aggagagaaa gggaaaatcg gtgagactct agtcttgcca 600aaaagtgctt tcactgtggg gctcacggtg ctgagcaagt ttccttcttc agatatgccc 660attaaatttg ataagatcct gtataacgaa ttcaaccatt atgatacagc agcggggaaa 720ttcacgtgcc acattgctgg ggtctattac ttcacctacc acatcactgt tttctccaga 780aatgttcagg tgtctttggt caaaaatgga gtaaaaatac tgcacaccaa agatgcttac 840atgagctctg aggaccaggc ctctggcggc attgtcctgc agctgaagct cggggatgag 900gtgtggctgc aggtgacagg aggagagagg ttcaatggct tgtttgctga tgaggacgat 960gacacaactt tcacagggtt ccttctgttc agcagcccgt ga 1002<210>15<211>678<212>DNA<213>人(Homo sapiens)<400>15atgaggatct ggtggcttct gcttgccatt gaaatctgca cagggaacat aaactcacag 60gacacctgca ggcaagggca ccctggaatc cctgggaacc ccggtcacaa tggtctgcct120ggaagagatg gacgagacgg agcgaagggt gacaaaggcg atgcaggaga agctggaccc180acggggcccc agggtgagcc aggagtccgg ggaataagag gctggaaagg agatcgagga240gagaaaggga aaatcggtga gactctagtc ttgccaaaaa gtgctttcac tgtggggctc300acggtgctga gcaagtttcc ttcttcagat atgcccatta aatttgataa gatcctgtat360aacgaattca accattatga tacagcagcg gggaaattca cgtgccacat tgctggggtc420tattacttca cctaccacat cactgttttc tccagaaatg ttcaggtgtc tttggtcaaa480aatggagtaa aaatactgca caccaaagat gcttacatga gctctgagga ccaggcctct540ggcggcattg tcctgcagct gaagctcggg gatgaggtgt ggctgcaggt gacaggagga600gagaggttca atggcttgtt tgctgatgag gacgatgaca caactttcac agggttcctt660ctgt tcagca gcccgtga 678<210>16<211>618<212>DNA<213>人(Homo sapiens)<400>16atgatgagaa ctctcatcac cacacaccca ctgcccctgc ttctattgcc gcagcagctg 60ctgcagctgg tgcagtttca agaggtggat acagattttg atttcccaga agaagataaa120aaagaagaat ttgaagagtg tttggaaaaa ttttttagta cagggcccgc cagaccacct180accaaagaaa aagtcaaaag acgtgtcctt attgaacctg gaatgccact aaatcatata240gagtactgta accatgaaat catgggaaaa aatgtttact acaaacaccg ttgggtggca300gaacattact tccttcttat gcaatatgac gagctccaaa aaatctgtta caacagattt360gtgccatgta agaatggaat taggaaatgt aacaggagca aaggtcttgt agaaggagtg420tattgtaatt taacagaagc atttgaaata ccagcgtgta aatacgaatc actttatagg480aagggctacg tccttatcac ttgttcatgg caaaatgaaa tgcaaaaacg tattcctcat540actataaatg atctcgtgga gccacctgaa cacagaagtt tcctcagtga ggatggtgtc600tttgtcatat cgccctag 618<210>17<211>288<212>DNA<213>人(Homo sapiens)<400>17atggaggtgg tgctgatctt tctatgcagc ctgttggccc acattgtcct ggccgatgca 60gttgagaggg agaagcaaat tgaccctttt cattatgact accagaccct gaggattagg120gggttggtat gtgctgtggt cctcttctcc attgggatcc tccttatcct aggttgcaga180tgcaagtgca gtttcaatca gaagcccagg accccaggag aggaggaagc ccaggtggag240aacctcatca ctgcaaatgc aacaaagctc cagaaagcag agagctga 288<210>18<211>1788<212>DNA<213>人(Homo sapiens)<400>18atggaggtgg gaatgggatg ctgggcccgg gaggtgctgg tccccgaggg gcccttgtac 60cgcgtggctg gcacagctgt ctccatctcc tgcaatgtga ccggctatga gggccctgcc120cagcagaact tcgagtggtt cctgtatagg cccgaggccc cagatactgc actgggcatt180gtcagtacca aggataccca gttctcctat gctgtcttca agtcccgagt ggtggcgggt240gaggtgcagg tgcagcgcct acaaggtgat gccgtggtgc tcaagattgc ccgcctgcag300gcccaggatg ccggcattta tgagtgccac accccctcca ctgatacccg ctacctgggc360agctacagcg gcaaggtgga gctgagagtt cttccagatg tcctccaggt gtctgctgcc420cccccagggc cccgaggccg ccaggcccca acctcacccc cacgcatgac ggtgcatgag480gggcaggagc tggcactggg ctgcctggcg aggacaagca cacagaagca cacacacctg540gcagtgtcct ttgggcgatc tgtgcccgag gcaccagttg ggcggtcaac tctgcaggaa600gtggtgggaa tccggtcaga cttggccgtg gaggctggag ctccctatgc tgagcgattg660gctgcagggg agcttcgtct gggcaaggaa gggaccgatc ggtaccgcat ggtagtaggg720ggtgcccagg caggggacgc aggcacctac cactgcactg ccgctgagtg gattcaggat 780cctgatggca gctgggccca gattgcagag aaaagggccg tcctggccca cgtggatgtg 840cagacgctgt ccagccagct ggcagtgaca gtggggcctg gtgaacgtcg gatcggccca 900ggggagccct tggaactgct gtgcaatgtg tcaggggcac ttcccccagc aggccgtcat 960gctgcatact ctgtaggttg ggagatggca cctgcggggc acctggggcc cggccgcctg1020gtagcccagc tggacacaga gggtgtgggc agcctgggcc ctggctatga gggccgacac1080attgccatgg agaaggtggc atccagaaca taccggctac ggctagaggc tgccaggcct1140ggtgatgcgg gcacctaccg ctgcctcgcc aaagcctatg ttcgagggtc tgggacccgg1200cttcgtgaag cagccagtgc ccgttcccgg cctctccctg tacatgtgcg ggaggaaggt1260gtggtgctgg aggctgtggc atggctagca ggaggcacag tgtaccgcgg ggagactgcc1320tccctgctgt gcaacatctc tgtgcggggt ggccccccag gactgcggct ggccgccagc1380tggtgggtgg agcgaccaga ggacggagag ctcagctctg tccctgccca gctggtgggt1440ggcgtaggcc aggatggtgt ggcagagctg ggagtccggc ctggaggagg ccctgtcagc1500gtagagctgg tggggccccg aagccatcgg ctgagactac acagcttggg gcccgaggat1560gaaggcgtgt accactgtgc ccccagcgcc tgggtgcagc atgccgacta cagctggtac1620caggcgggca gtgcccgctc agggcctgtt acagtctacc cctacatgca tgccctggac1680accctatttg tgcctctgct ggtgggtaca ggggtggccc tagtcactgg tgccactgtc1740cttggtacca tcacttgctg cttcatgaag aggcttcgaa aacggtga 1788<210>19<211>1842<212>DNA<213>人(Homo sapiens)<400>19atgggcgccc tcaggcccac gctgctgccg ccttcgctgc cgctgctgct gctgctaatg 60ctaggaatgg gatgctgggc ccgggaggtg ctggtccccg aggggccctt gtaccgcgtg 120gctggcacag ctgtctccat ctcctgcaat gtgaccggct atgagggccc tgcccagcag 180aacttcgagt ggttcctgta taggcccgag gccccagata ctgcactggg cattgtcagt 240accaaggata cccagttctc ctatgctgtc ttcaagtccc gagtggtggc gggtgaggtg 300caggtgcagc gcctacaagg tgatgccgtg gtgctcaaga ttgcccgcct gcaggcccag 360gatgccggca tttatgagtg ccacaccccc tccactgata cccgctacct gggcagctac 420agcggcaagg tggagctgag agttcttcca gatgtcctcc aggtgtctgc tgccccccca 480gggccccgag gccgccaggc cccaacctca cccccacgca tgacggtgca tgaggggcag 540gagctggcac tgggctgcct ggcgaggaca agcacacaga agcacacaca cctggcagtg 600tcctttgggc gatctgtgcc cgaggcacca gttgggcggt caactctgca ggaagtggtg 660ggaatccggt cagacttggc cgtggaggct ggagctccct atgctgagcg attggctgca 720ggggagcttc gtctgggcaa ggaagggacc gatcggtacc gcatggtagt agggggtgcc 780caggcagggg acgcaggcac ctaccactgc actgccgctg agtggattca ggatcctgat 840ggcagctggg cccagattgc agagaaaagg gccgtcctgg cccacgtgga tgtgcagacg 900ctgtccagcc agctggcagt gacagtgggg cctggtgaac gtcggatcgg cccaggggag 960cccttggaac tgctgtgcaa tgtgtcaggg gcacttcccc cagcaggccg tcatgctgca1020tactctgtag gttgggagat ggcacctgcg ggggcacctg ggcccggccg cctggtagcc1080cagctggaca cagagggtgt gggcagcctg ggccctggct atgagggccg acacattgcc1140atggagaagg tggcatccag aacataccgg ctacggctag aggctgccag gcctggtgat1200gcgggcacct accgctgcct cgccaaagcc tatgttcgag ggtctgggac ccggcttcgt1260gaagcagcca gtgcccgttc ccggcctctc cctgtacatg tgcgggagga aggtgtggtg1320ctggaggctg tggcatggct agcaggaggc acagtgtacc gcggggagac tgcctccctg1380ctgtgcaaca tctctgtgcg gggtggcccc ccaggactgc ggctggccgc cagctggtgg1440gtggagcgac cagaggacgg agagctcagc tctgtccctg cccagctggt gggtggcgta1500ggccaggatg gtgtggcaga gctgggagtc cggcctggag gaggccctgt cagcgtagag1560ctggtggggc cccgaagcca tcggctgaga ctacacagct tggggcccga ggatgaaggc1620gtgtaccact gtgcccccag cgcctgggtg cagcatgccg actacagctg gtaccaggcg1680ggcagtgccc gctcagggcc tgttacagtc tacccctaca tgcatgccct ggacacccta1740tttgtgcctc tgctggtggg tacaggggtg gccctagtca ctggtgccac tgtccttggt1800accatcactt gctgcttcat gaagaggctt cgaaaacggt ga 1842<210>20<211>1791<212>DNA<213>人(Homo sapiens)<400>20atggccgcca actccaccag cgacctccac actcccggga cgcagctgag cgtggctgac 60atcatcgtca tcactgtgta ttttgctctg aacgtggccg tgggcatatg gtcctcttgt 120cgggccagta ggaacacggt gaatggctac ttcctggcag gccgggacat gacgtggtgg 180ccgattggag cctccctctt cgccagcagc gagggctctg gcctcttcat tggactggcg 240ggctcaggcg cggcaggagg tctggccgtg gcaggcttcg agtggaatgc cacgtacgtg 300ctgctggcac tggcatgggt gttcgtgccc atctacatct cctcagagat cgtcacctta 360cctgagtaca ttcagaagcg ctacgggggc cagcggatcc gcatgtacct gtctgtcctg 420tccctgctac tgtctgtctt caccaagata tcgctggacc tgtacgcggg ggctctgttt 480gtgcacatct gcctgggctg gaacttctac ctctccacca tcctcacgct cggcatcaca 540gccctgtaca ccatcgcagg gggcctggct gctgtaatct acacggacgc cctgcagacg 600ctcatcatgg tggtgggggc tgtcatcctg acaatcaaag cttttgacca gatcggtggt 660tacgggcagc tggaggcagc ctacgcccag gccattccct ccaggaccat tgccaacacc 720acctgccacc tgccacgtac agacgccatg cacatgtttc gagaccccca cacaggggac 780ctgccgtgga ccgggatgac ctttggcctg accatcatgg ccacctggta ctggtgcacc 840gaccaggtca tcgtgcagcg atcactgtca gcccgggacc tgaaccatgc caaggcgggc 900tccatcctgg ccagctacct caagatgctc cccatgggcc tgatcataat gccgggcatg 960atcagccgcg cattgttccc agatgatgtg ggctgcgtgg tgccgtccga gtgcctgcgg1020gcctgcgggg ccgaggtcgg ctgctccaac atcgcctacc ccaagctggt catggaactg1080atgcccatcg gtctgcgggg gctgatgatc gcagtgatgc tggcggcgct catgtcgtcg1140ctgacctcca tcttcaacag cagcagcacc ctcttcacta tggacatctg gaggcggctg1200cgtccccgct ccggcgagcg ggagctcctg ctggtgggac ggctggtcat agtggcactc1260atcggcgtga gtgtggcctg gatccccgtc ctgcaggact ccaacagcgg gcaactcttc1320atctacatgc agtcagtgac cagctccctg gccccaccag tgactgcagt ctttgtcctg1380ggcgtcttct ggcgacgtgc caacgagcag ggggccttct ggggcctgat agcagggctg1440gtggtggggg ccacgaggct ggtcctggaa ttcctgaacc cagccccacc gtgcggagag1500ccagacacgc ggccagccgt cctggggagc atccactacc tgcacttcgc tgtcgccctc1560tttgcactca gtggtgctgt tgtggtggct ggaagcctgc tgaccccacc cccacagagt1620gtccagattg agaaccttac ctggtggacc ctggctcagg atgtgccctt gggaactaaa1680gcaggtgatg gccaaacacc ccagaaacac gccttctggg cccgtgtctg tggcttcaat1740gccatcctcc tcatgtgtgt caacatattc ttttatgcct acttcgcctg a 1791<210>21<211>1182<212>DNA<213>人(Homo sapiens)<400>21atggattcct taaagaatga gaactatgat ctggtatttg ttgaagcatt tgatttctgt 60tctttcctga ttgctgagaa gcttgtgaaa ccatttgtgg ccattcttcc caccacattc 120ggctctttgg attttgggct accaagcccc ttgtcttatg ttccagtatt cccttccttg 180ctgactgatc acatggactt ctggggccga gtgaagaatt ttctgatgtt ctttagtttc 240tccaggagcc aatgggacat gcagtctaca tttgacaaca ccatcaagga gcatttccca 300gaaggctcta ggccagtttt gtctcatctt ctactgaaag cagagttgtg gtttgttaac 360tctgattttg cctttgattt tgcccggccc ctgcttccca acactgttta tattggaggc 420ttgatggaaa aacctattaa accagtacca caagacttgg acaacttcat tgccaacttt 480ggggatgcag ggtttgtcct tgtggccttt ggctccatgt tgaacaccca tcagtcccag 540gaagtcctca agaagatgca caatgccttt gcccacctcc ctcaaggagt gatatggaca 600tgtcagagtt ctcattggcc cagagatgtt catttggcca caaatgtgaa aattgtggac 660tggcttcctc agagtgacct cctggctcac cccagcatcc gtctttttgt cactcatggt 720gggcagaaca gcgtaatgga ggccatccgt catggtgtgc ccatggtggg attaccagtc 780aatggagacc agcatggaaa catggtccga gtagtagcca aaaattatgg tgtctctatc 840cggttgaatc aggtcacagc cgacacactg acacttacaa tgaaacaagt catagaagac 900aagaggtaca agtcggcagt ggtggcagcc agtgtcatcc tgcactctca gcccctgagc 960cccgcacagc ggctggtggg ctggatcgac cacatcctcc agactggggg agcgacgcac1020ctcaagccct atgccttcca gcagccttgg catgagcagt acctcattga tgtctttgtg1080tttctgctgg ggctcactct gggcactatg tggctttgtg ggaagctgct gggtgtggtg1140gccaggtggc tgcgtggggc caggaaggtg aagaagacat ga 1182<210>22<211>1572<212>DNA<213>人(Homo sapiens)<400>22atggttgggc agcgggtgct gcttctagtg gccttccttc tttctggggt cctgctctca 60gaggctgcca aaatcctgac aatatctaca ctgggtggaa gccattacct actgttggac 120cgggtgtctc agattcttca agagcatggt cataatgtga ctatgcttca tcagagtgga 180aagtttttga tcccagatat taaagaggag gaaaaatcat accaagttat caggtggttt 240tcacctgaag atcatcaaaa aagaattaag aagcattttg atagctacat agaaacagca 300ttggatggca gaaaagaatc tgaagccctt gtaaagctaa tggaaatatt tgggactcaa 360tgtagttatt tgctaagcag aaaggatata atggattcct taaagaatga gaactatgat 420ctggtatttg ttgaagcatt tgatttctgt tctttcctga ttgctgagaa gcttgtgaaa 480ccatttgtgg ccattcttcc caccacattc ggctctttgg attttgggct accaagcccc 540ttgtcttatg ttccagtatt cccttccttg ctgactgatc acatggactt ctggggccga 600gtgaagaatt ttctgatgtt ctttagtttc tccaggagcc aatgggacat gcagtctaca 660tttgacaaca ccatcaagga gcatttccca gaaggctcta ggccagtttt gtctcatctt 720ctactgaaag cagagttgtg gtttgttaac tctgattttg cctttgattt tgcccggccc 780ctgcttccca acactgttta tattggaggc ttgatggaaa aacctattaa accagtacca 840caagacttgg acaacttcat tgccaacttt ggggatgcag ggtttgtcct tgtggccttt 900ggctccatgt tgaacaccca tcagtcccag gaagtcctca agaagatgca caatgccttt 960gcccacctcc ctcaaggagt gatatggaca tgtcagagtt ctcattggcc cagagatgtt1020catttggcca caaatgtgaa aattgtggac tggcttcctc agagtgacct cctggctcac1080cccagcatcc gtctttttgt cactcatggt gggcagaaca gcgtaatgga ggccatccgt1140catggtgtgc ccatggtggg attaccagtc aatggagacc agcatggaaa catggtccga1200gtagtagcca aaaattatgg tgtctctatc cggttgaatc aggtcacagc cgacacactg1260acacttacaa tgaaacaagt catagaagac aagaggtaca agtcggcagt ggtggcagcc1320agtgtcatcc tgcactctca gcccctgagc cccgcacagc ggctggtggg ctggatcgac1380cacatcctcc agactggggg agcgacgcac ctcaagccct atgccttcca gcagccttgg1440catgagcagt acctcattga tgtctttgtg tttctgctgg ggctcactct gggcactatg1500tggctttgtg ggaagctgct gggtgtggtg gccaggtggc tgcgtggggc caggaaggtg1560aagaagacat ga1572<210>23<211>759<212>DNA<213>人(Homo sapiens)<400>23atgagctgcg tcctgggtgg tgtcatcccc ttggggctgc tgttcctggt ctgcggatcc 60caaggctacc tcctgcccaa cgtcactctc ttagaggagc tgctcagcaa ataccagcac 120aacgagtctc actcccgggt ccgcagagcc atccccaggg aggacaagga ggagatcctc 180atgctgcaca acaagcttcg gggccaggtg cagcctcagg cctccaacat ggagtacatg 240acctgggatg acgaactgga gaagtctgct gcagcgtggg ccagtcagtg catctgggag 300cacgggccca ccagtctgct ggtgtccatc gggcagaacc tgggcgctca ctggggcagg 360tatcgctctc cggggttcca tgtgcagtcc tggtatgacg aggtgaagga ctacacctac 420ccctacccga gcgagtgcaa cccctggtgt ccagagaggt gctcggggcc catgtgcacg 480cactacacac agatagtttg ggccaccacc aacaagatcg gttgtgctgt gaacacctgc 540cggaagatga ctgtctgggg agaagtttgg gagaacgcgg tctactttgt ctgcaattat 600tctccaaagg ggaactggat tggagaagcc ccctacaaga atggccggcc ctgctctgag 660tgcccaccca gctatggagg cagctgcagg aacaacttgt gttaccgagg taggaaattt 720actcccaaca cttttgcaat gaatttgccc tcagtctga759<210>24<211>1494<212>DNA<213>人(Homo sapiens)<400>24atgagctgcg tcctgggtgg tgtcatcccc ttggggctgc tgttcctggt ctgcggatcc 60caaggctacc tcctgcccaa cgtcactctc ttagaggagc tgctcagcaa ataccagcac 120aacgagtctc actcccgggt ccgcagagcc atccccaggg aggacaagga ggagatcctc 180atgctgcaca acaagcttcg gggccaggtg cagcctcagg cctccaacat ggagtacatg 240acctgggatg acgaactgga gaagtctgct gcagcgtggg ccagtcagtg catctgggag 300cacgggccca ccagtctgct ggtgtccatc gggcagaacc tgggcgctca ctggggcagg 360tatcgctctc cggggttcca tgtgcagtcc tggtatgacg aggtgaagga ctacacctac 420ccctacccga gcgagtgcaa cccctggtgt ccagagaggt gctcggggcc catgtgcacg 480cactacacac agatagtttg ggccaccacc aacaagatcg gttgtgctgt gaacacctgc 540cggaagatga ctgtctgggg agaagtttgg gagaacgcgg tctactttgt ctgcaattat 600tctccaaagg ggaactggat tggagaagcc ccctacaaga atggccggcc ctgctctgag 660tgcccaccca gctatggagg cagctgcagg aacaacttgt gttaccgaga agaaacctac 720actccaaaac ctgaaacgga cgagatgaat gaggtggaaa cggctcccat tcctgaagaa 780aaccatgttt ggctccaacc gagggtgatg agacccacca agcccaagaa aacctctgcg 840gtcaactaca tgacccaagt cgtcagatgt gacaccaaga tgaaggacag gtgcaaaggg 900tccacgtgta acaggtacca gtgcccagca ggctgcctga accacaaggc gaagatcttt 960ggaactctgt tctatgaaag ctcgtctagc atatgccgcg ccgccatcca ctacgggatc1020ctggatgaca agggaggcct ggtggatatc accaggaacg ggaaggtccc cttcttcgtg1080aagtctgaga gacacggcgt gcagtccctc agcaaataca aaccttccag ctcattcatg1140gtgtcaaaag tgaaagtgca ggatttggac tgctacacga ccgttgctca gctgtgcccg1200tttgaaaagc cagcaactca ctgcccaaga atccattgtc cggcacactg caaagacgaa1260ccttcctact gggctccggt gtttggaacc aacatctatg cagatacctc aagcatctgc1320aagacagccg tgcacgcggg agtcatcagc aacgagagtg ggggtgacgt ggacgtgatg1380cccgtggata aaaagaagac ctacgtgggc tcgctcagga atggagttca gtctgaaagc1440ctggggactc ctcgggatgg aaaggccttc cggatctttg ctgtcaggca gtga 1494<210>25<211>1315<212>DNA<213>人(Homo sapiens)<400>25batgctgcac aacaagcttc ggggccaggt gcagcctcag gcctccaaca tggagtacat 60gacctgggat gacgaactgg agaagtctgc tgcagcgtgg gccagtcagt gcatctggga 120gcacgggccc accagtctgc tggtgtccat cgggcagaac ctgggcgctc actggggcag 180gtatcgctct ccggggttcc atgtgcagtc ctggtatgac gaggtgaagg actacaccta 240cccctacccg agcgagtgca acccctggtg tccagagagg tgctcggggc ccatgtgcac 300gcactacaca cagatagttt gggccaccac caacaagatc ggttgtgctg tgaacacctg 360ccggaagatg actgtctggg gagaagtttg ggagaacgcg gtctactttg tctgcaatta 420ttctccaaag gggaactgga ttggagaagc cccctacaag aatggccggc cctgctctga 480gtgcccaccc agctatggag gcagctgcag gaacaacttg tgttaccgag aagaaaccta 540cactccaaaa cctgaaacgg acgagatgaa tgaggtggaa acggctccca ttcctgaaga 600aaaccatgtt tggctccaac cgagggtgat gagacccacc aagcccaaga aaacctctgc 660ggtcaactac atgacccaag tcgtcagatg tgacaccaag atgaaggaca ggtgcaaagg 720gtccacgtgt aacaggtacc agtgcccagc aggctgcctg aaccacaagg cgaagatctt 780tggaactctg ttctatgaaa gctcgtctag catatgccgc gccgccatcc actacgggat 840cctggatgac aagggaggcc tggtggatat caccaggaac gggaaggtcc ccttcttcgt 900gaagtctgag agacacggcg tgcagtccct cagcaaatac aaaccttcca gctcattcat 960ggtgtcaaaa gtgaaagtgc aggatttgga ctgctacacg accgttgctc agctgtgccc1020gtttgaaaag ccagcaactc actgcccaag aatccattgt ccggcacact gcaaagacga1080accttcctac tgggctccgg tgtttggaac caacatctat gcagatacct caagcatctg1140caagacagcc gtgcacgcgg gagtcatcag caacgagagt gggggtgacg tggacgtgat1200gcccgtggat aaaaagaaga cctacgtggg ctcgctcagg aatggagttc agtctgaaag1260cctggggact cctcgggatg gaaaggcctt ccggatcttt gctgtcaggc agtga 1315<210>26<211>927<212>DNA<213>人(Homo sapiens)<400>26atggttgggg gcgtcctcgc ctcgctgggc ttcgtcttct cggctttcgc cagcgatctg 60ctgcatctct acctcggcct gggcctcctc gctggctttg gttgggccct ggtgttcgcc 120cccgccctag gcaccctctc gcgttacttc tcccgccgtc gagtcttggc ggtggggctg 180gcgctcaccg gcaacggggc ctcctcgctg ctcctggcgc ccgccttgca gcttcttctc 240gatactttcg gctggcgggg cgctctgctc ctcctcggcg cgatcaccct ccacctcacc 300ccctgtggcg ccctgctgct acccctggtc cttcctggag accccccagc cccaccgcgt 360agtcccctag ctgccctcgg cctgagtctg ttcacacgcc gggccttctc aatctttgct 420ctaggcacag ccctggttgg gggcgggtac ttcgttcctt acgtgcactt ggctccccac 480gctttagacc ggggcctggg gggatacgga gcagcgctgg tggtggccgt ggctgcgatg 540ggggatgcgg gcgcccggct ggtctgcggg tggctggcag accaaggctg ggtgcccctc 600ccgcggctgc tggccgtatt cggggctctg actgggctgg ggctgtgggt ggtggggctg 660gtgcccgtgg tgggcggcga agagagctgg gggggtcccc tgctggccgc ggctgtggcc 720tatgggctga gcgcggggag ttacgccccg ctggttttcg gtgtactccc cgggctggtg 780ggcgtcggag gtgtggtgca ggccacaggg ctggtgatga tgctgatgag cctcgggggg 840ctcctgggcc ctcccctgtc aggtaaggac ctgagctcac agatctgcct acaactatcc 900tctgcccctg gggttcgagg cttctaa 927<210>27<211>1344<212>DNA<213>人(Homo sapiens)<400>27atgacccccc agcccgccgg acccccggat gggggctggg gctgggtggt ggcggccgca 60gccttcgcga taaacgggct gtcctacggg ctgctgcgct cgctgggcct tgccttccct 120gaccttgccg agcactttga ccgaagcgcc caggacactg cgtggatcag cgccctggcc 180ctggccgtgc agcaggcagc cagccccgtg ggcagcgccc tgagcacgcg ctggggggcc 240cgccccgtgg tgatggttgg gggcgtcctc gcctcgctgg gcttcgtctt ctcggctttc 300gccagcgatc tgctgcatct ctacctcggc ctgggcctcc tcgctggctt tggttgggcc 360ctggtgttcg cccccgccct aggcaccctc tcgcgttact tctcccgccg tcgagtcttg 420gcggtggggc tggcgctcac cggcaacggg gcctcctcgc tgctcctggc gcccgccttg 480cagcttcttc tcgatacttt cggctggcgg ggcgctctgc tcctcctcgg cgcgatcacc 540ctccacctca ccccctgtgg cgccctgctg ctacccctgg tccttcctgg agacccccca 600gccccaccgc gtagtcccct agctgccctc ggcctgagtc tgttcacacg ccgggccttc 660tcaatctttg ctctaggcac agccctggtt gggggcgggt acttcgttcc ttacgtgcac 720ttggctcccc acgctttaga ccggggcctg gggggatacg gagcagcgct ggtggtggcc 780gtggctgcga tgggggatgc gggcgcccgg ctggtctgcg ggtggctggc agaccaaggc 840tgggtgcccc tcccgcggct gctggccgta ttcggggctc tgactgggct ggggctgtgg 900gtggtggggc tggtgcccgt ggtgggcggc gaagagagct gggggggtcc cctgctggcc 960gcggctgtgg cctatgggct gagcgcgggg agttacgccc cgctggtttt cggtgtactc1020cccgggctgg tgggcgtcgg aggtgtggtg caggccacag ggctggtgat gatgctgatg1080agcctcgggg ggctcctggg ccctcccctg tcaggcttcc taagggatga gacaggagac1140ttcaccgcct ctttcctcct gtctggttct ttgatcctct ccggcagctt catctacata1200gggttgccca gggcgctgcc ctcctgtggt ccagcctccc ctccagccac gcctccccca1260gagacggggg agctgcttcc cgctccccag gcagtcttgc tgtccccagg aggccctggc1320tccactctgg acaccacttg ttga 1344<210>28<211>1375<212>DNA<213>人(Homo sapiens)<400>28batggcgcgc aggacagagc cccccgacgg gggctgggga tgggtggtgg tgctctcagc 60gttcttccag tcggcgcttg tgtttggggt gctccgctcc tttggggtct tcttcgtgga 120gtttgtggcg gcgtttgagg agcaggcagc gcgcgtctcc tggatcgcct ccataggaat 180cgcggtgcag cagtttggga gcccggtagg cagtgccctg agcacgaagt tcgggcccag 240gcccgtggtg atgactggag gcatcttggc tgcgctgggg atgctgctcg cctcttttgc 300tacttccttg acccacctat acctgagtat tgggttgctg tcaggctctg gctgggcttt 360gaccttcgct ccgaccctgg cctgcctgtc ctgttatttc tctcgccgac gatccctggc 420caccgggctg gcactgacag gcgtgggcct ctcctccttc acatttgccc cctttttcca 480gtggctgctc agccactacg cctggagggg gtccctgctg ctggtgtctg ccctctccct 540ccacctagtg gcctgtggtg ctctcctccg cccaccctcc ctggctgagg accctgctgt 600gggtggtccc agggcccaac tcacctctct cctccatcat ggccccttcc tccgttacac 660tgttgccctc accctgatca acactggcta cttcattccc tacctccacc tggtggccca 720tctccaggac ctggattggg acccactacc tgctgccttc ctactctcag ttgttgctat 780ttctgacctc gtggggcgtg tggtctccgg atggctggga gatgcagtcc cagggcctgt 840gacacgactc ctgatgctct ggaccacctt gactggggtg tcactagccc tgttccctgt 900agctcaggct cccacagccc tggtggctct ggctgtggcc tacggcttca catcaggggc 960tctggcccca ctggccttct ccgtgctgcc tgaactaata gggactagaa ggatttactg1020tggcctggga ctgttgcaga tgatagagag catcgggggg ctgctggggc ctcctctctc1080aggctacctc cgggatgtgt caggcaacta cacggcttct tttgtggtgg ctggggcctt1140ccttctttca gggagtggca ttctcctcac cctgccccac ttcttctgct tctcaactac1200tacctccggg cctcaggacc ttgtaacaga agcactagat actaaagttc ccctacccaa1260ggaggggctg gaaggaggac tgaactccac agagtcaggc ccagaaagcc aaagcttgac1320agctccaggt cttctcttgc cacgtcttgg tctccacaga accacagtgc cttaa 1375<210>29<211>510<212>DNA<213>人(Homo sapiens)<400>29atgaccatga agacctctgg ggccacttgt gatgcaaaca gtgtgatgaa ctgcgggatc 60cgcgggtctg aaatgtttgc tgagatggat ttgagggcca taaaacctta ccagactctg 120atcaaaaaag tcgggcagag acattgcgtg gaccctgctg tcatcgcagc catcatctcc 180agggaaagcc atgggggatc tgtcctgcaa gacggctggg accacagggg acttaaattt 240ggcttgatgc agcttgataa acaaacgtac caccctgtcg gtgcctggga tagcaaagag 300cacctttcac aggctactgg gattctaaca gagagaatta aggcaatcca gaaaaaattc 360cccacgtgga gtgttgctca gcacctcaaa ggtggtctct cagcttttaa gtcaggaatt 420gaagcgattg ccaccccatc ggacatagac aatgacttcg tcaatgatat cattgctcga 480gctaagttct ataaaagaca aagcttctag 510<210>30<211>561<212>DNA<213>人(Homo sapiens)<400>30atgaagcctc acctacatcc acgcctgtac cacggctgct atggggacat catgaccatg 60aagacctctg gggccacttg tgatgcaaac agtgtgatga actgcgggat ccgcgggtct 120gaaatgtttg ctgagatgga tttgagggcc ataaaacctt accagactct gatcaaaaaa 180gtcgggcaga gacattgcgt ggaccctgct gtcatcgcag ccatcatctc cagggaaagc 240catgggggat ctgtcctgca agacggctgg gaccacaggg gacttaaatt tggcttgatg 300cagcttgata aacaaacgta ccaccctgtc ggtgcctggg atagcaaaga gcacctttca 360caggctactg ggattctaac agagagaatt aaggcaatcc agaaaaaatt ccccacgtgg 420agtgttgctc agcacctcaa aggtggtctc tcagctttta agtcaggaat tgaagcgatt 480gccaccccat cggacataga caatgacttc gtcaatgata tcattgctcg agctaagttc 540tataaaagac aaagcttcta g 561<210>31<211>2028<212>DNA<213>人(Homo sapiens)<400>31atggagagcg gcaccagcag ccctcagcct ccacagttag atcccctgga tgcgtttccc 60cagaagggct tggagcctgg ggacatcgcg gtgctagttc tgtacttcct ctttgtcctg 120gctgttggac tatggtccac agtgaagacc aaaagagaca cagtgaaagg ctacttcctg 180gctggagggg acatggtgtg gtggccagtg ggtgcatcct tgtttgccag caatgttgga 240agtggacatt tcattggcct ggcagggtca ggtgctgcta cgggcatttc tgtatcagct 300tatgaactta atggcttgtt ttctgtgctg atgttggcct ggatcttcct acccatctac 360attgctggtc aggtcaccac gatgccagaa tacctacgga agcgcttcgg tggcatcaga 420atccccatca tcctggctgt actctaccta tttatctaca tcttcaccaa gatctcggta 480gacatgtatg caggtgccat cttcatccag cagtctttgc acctggatct gtacctggcc 540atagttgggc tactggccat cactgctgta tacacggttg ctggtggcct ggctgctgtg 600atctacacgg atgccctgca gacgctgatc atgcttatag gagcgctcac cttgatgggc 660tacagtttcg ccgcggttgg tgggatggaa ggactgaagg agaagtactt cttggccctg 720gctagcaacc ggagtgagaa cagcagctgc gggctgcccc gggaagatgc cttccatatt 780ttccgagatc cgctgacatc tgatctcccg tggccggggg tcctatttgg aatgtccatc 840ccatccctct ggtactggtg cacggatcag gtgattgtcc agcggactct ggctgccaag 900aacctgtccc atgccaaagg aggtgctctg atggctgcat acctgaaggt gctgcccctc 960ttcataatgg tgttccctgg gatggtcagc cgcatcctct tcccagatca agtggcctgt1020gcagatccag agatctgcca gaagatctgc agcaacccct caggctgttc ggacatcgcg1080tatcccaaac tcgtgctgga actcctgccc acagggctcc gtgggctgat gatggctgtg1140atggtggcgg ctctcatgtc ctccctcacc tccatcttta acagtgccag caccatcttc1200accatggacc tctggaatca cctccggcct cgggcatctg agaaggagct catgattgtg1260ggcagggtgt ttgtgctgct gctggtcctg gtctccatcc tctggatccc tgtggtccag1320gccagccagg gcggccagct cttcatctat atccagtcca tcagctccta cctgcagccg1380cctgtggcgg tggtcttcat catgggatgt ttctggaaga ggaccaatga aaagggtgcc1440ttctggggcc tgatctcggg cctgctcctg ggcttggtta ggctggtcct ggactttatt1500tacgtgcagc ctcgatgcga ccagccagat gagcgcccgg tcctggtgaa gagcattcac1560tacctctact tctccatgat cctgtccacg gtcaccctca tcactgtctc caccgtgagc1620tggttcacag agccaccctc caaggagatg gtcagccacc tgacctggtt tactcgtcac1680gaccccgtgg tccagaagga acaagcacca ccagcagctc ccttgtctct taccctctct1740cagaacggga tgccagaggc cagcagcagc agcagcgtcc agttcgagat ggttcaagaa1800aacacgtcta aaacccacag ctgtgacatg accccaaagc agtccaaagt ggtgaaggcc1860atcctgtggc tctgtggaat acaggagaag ggcaaggaag agctcccggc cagagcagaa1920gccatcatag tttccctgga agaaaacccc ttggtgaaga ccctcctgga cgtcaacctc1980attttctgcg tgagctgcgc catctttatc tggggctatt ttgcttag 2028<210>32<211>1458<212>DNA<213>人(Homo sapiens)<400>32atggagccct gttggggaga aggcttgttt catctagcac ccccacgcca ccatccccag 60aaggctgact ggcatttctg tccacagcac attcaggaat tcaccaatga gacatggcag 120gcgcgtactg gagagccact gcccgatcac ctagtcctgc ttatgtggtc cctcatcgtg 180tctctgtatc ccctgggagg cctctttgga gcactgcttg caggtccctt ggccatcacg 240ctgggaagga agaagtccct cctggtgaat aacatctttg tggtgtcagc agcaatcctg 300tttggattca gccgcaaagc aggctccttt gagatgatca tgctgggaag actgctcgtg 360ggagtcaatg caggtgtgag catgaacatc cagcccatgt acctggggga gagcgcccct 420aaggagctcc gaggagctgt ggccatgagc tcagccatct ttacggctct ggggatcgtg 480atgggacagg tggtcggact cagggagctc ctaggtggcc ctcaggcctg gcccctgctg 540ctggccagct gcctggtgcc cggggcgctc cagctcgcct ccctgcctct gctccctgaa 600agcccgcgct acctcctcat tgactgtgga gacaccgagg cctgcctggc agcactacgg 660cggctccggg gctccgggga cttggcaggg gagctggagg agctggagga ggagcgcgct 720gcctgccagg gctgccgtgc ccggcgccca tgggagctgt tccagcatcg ggccctgagg 780agacaggtga caagcctcgt ggttctgggc agtgccatgg agctctgcgg gaatgactcg 840gtgtacgcct acgcctcctc cgtgttccgg aaggcaggag tgccggaagc gaagatccag 900tacgcgatca tcgggactgg gagctgcgag ctgctcacgg cggttgttag ttgtgtggta 960atcgagaggg tgggtcggcg cgtgctgctc atcggtgggt acagcctgat gacctgctgg1020gggagcatct tcactgtggc cctgtgcctg cagagctcct tcccctggac actctacctg1080gccatggcct gcatctttgc cttcatcctc agctttggca ttggccctgc cggagtgacg1140gggatcctgg ccacagagct gtttgaccag atggccaggc ctgctgcctg catggtctgc1200ggggcgctca tgtggatcat gctcatcctg gtcggcctgg gatttccctt tatcatggag1260gccttgtccc acttcctcta tgtccctttc cttggtgtct gtgtctgtgg ggccatctac1320actggcctgt tccttcctga gaccaaaggc aagaccttcc aagagatctc caaggaatta1380cacagactca acttccccag gcgggcccag ggccccacgt ggaggagcct ggaggttatc1440cagtcaacag aactctag 1458<210>33<211>1491<212>DNA<213>人(Homo sapiens)<400>33atgagagcgc tccgaagact gattcagggc aggatcctgc tcctgaccat ctgcgctgcc 60ggcattggtg ggacttttca gtttggctat aacctctcta tcatcaatgc cccgaccttg 120cacattcagg aattcaccaa tgagacatgg caggcgcgta ctggagagcc actgcccgat 180cacctagtcc tgcttatgtg gtccctcatc gtgtctctgt atcccctggg aggcctcttt 240ggagcactgc ttgcaggtcc cttggccatc acgctgggaa ggaagaagtc cctcctggtg 300aataacatct ttgtggtgtc agcagcaatc ctgtttggat tcagccgcaa agcaggctcc 360tttgagatga tcatgctggg aagactgctc gtgggagtca atgcaggtgt gagcatgaac 420atccagccca tgtacctggg ggagagcgcc cctaaggagc tccgaggagc tgtggccatg 480agctcagcca tctttacggc tctggggatc gtgatgggac aggtggtcgg actcagggag 540ctcctaggtg gccctcaggc ctggcccctg ctgctggcca gctgcctggt gcccggggcg 600ctccagctcg cctccctgcc tctgctccct gaaagcccgc gctacctcct cattgactgt 660ggagacaccg aggcctgcct ggcagcacta cggcggctcc ggggctccgg ggacttggca 720ggggagctgg aggagctgga ggaggagcgc gctgcctgcc agggctgccg tgcccggcgc 780ccatgggagc tgttccagca tcgggccctg aggagacagg tgacaagcct cgtggttctg 840ggcagtgcca tggagctctg cgggaatgac tcggtgtacg cctacgcctc ctccgtgttc 900cggaaggcag gagtgccgga agcgaagatc cagtacgcga tcatcgggac tgggagctgc 960gagctgctca cggcggttgt tagttgtgtg gtaatcgaga gggtgggtcg gcgcgtgctg1020ctcatcggtg ggtacagcct gatgacctgc tgggggagca tcttcactgt ggccctgtgc1080ctgcagagct ccttcccctg gacactctac ctggccatgg cctgcatctt tgccttcatc1140ctcagctttg gcattggccc tgccggagtg acggggatcc tggccacaga gctgtttgac1200cagatggcca ggcctgctgc ctgcatggtc tgcggggcgc tcatgtggat catgctcatc1260ctggtcggcc tgggatttcc ctttatcatg gaggccttgt cccacttcct ctatgtccct1320ttccttggtg tctgtgtctg tggggccatc tacactggcc tgttccttcc tgagaccaaa1380ggcaagacct tccaagagat ctccaaggaa ttacacagac tcaacttccc caggcgggcc1440cagggcccca cgtggaggag cctggaggtt atccagtcaa cagaactcta g 1491<210>34<211>1501<212>DNA<213>人(Homo sapiens)<400>34batgctccac gccctcctgc gatctagaat gattcagggc aggatcctgc tcctgaccat 60ctgcgctgcc ggcattggtg ggacttttca gtttggctat aacctctcta tcatcaatgc 120cccgaccttg cacattcagg aattcaccaa tgagacatgg caggcgcgta ctggagagcc 180actgcccgat cacctagtcc tgcttatgtg gtccctcatc gtgtctctgt atcccctggg 240aggcctcttt ggagcactgc ttgcaggtcc cttggccatc acgctgggaa ggaagaagtc 300cctcctggtg aataacatct ttgtggtgtc agcagcaatc ctgtttggat tcagccgcaa 360agcaggctcc tttgagatga tcatgctggg aagactgctc gtgggagtca atgcaggtgt 420gagcatgaac atccagccca tgtacctggg ggagagcgcc cctaaggagc tccgaggagc 480tgtggccatg agctcagcca tctttacggc tctggggatc gtgatgggac aggtggtcgg 540actcagggag ctcctaggtg gccctcaggc ctggcccctg ctgctggcca gctgcctggt 600gcccggggcg ctccagctcg cctccctgcc tctgctccct gaaagcccgc gctacctcct 660cattgactgt ggagacaccg aggcctgcct ggcagcacta cggcggctcc ggggctccgg 720ggacttggca ggggagctgg aggagctgga ggaggagcgc gctgcctgcc agggctgccg 780tgcccggcgc ccatgggagc tgttccagca tcgggccctg aggagacagg tgacaagcct 840cgtggttctg ggcagtgcca tggagctctg cgggaatgac tcggtgtacg cctacgcctc 900ctccgtgttc cggaaggcag gagtgccgga agcgaagatc cagtacgcga tcatcgggac 960tgggagctgc gagctgctca cggcggttgt tagttgtgtg gtaatcgaga gggtgggtcg1020gcgcgtgctg ctcatcggtg ggtacagcct gatgacctgc tgggggagca tcttcactgt1080ggccctgtgc ctgcagagct ccttcccctg gacactctac ctggccatgg cctgcatctt1140tgccttcatc ctcagctttg gcattggccc tgccggagtg acggggatcc tggccacaga1200gctgtttgac cagatggcca ggcctgctgc ctgcatggtc tgcggggcgc tcatgtggat1260catgctcatc ctggtcggcc tgggatttcc ctttatcatg gaggccttgt cccacttcct1320ctatgtccct ttccttggtg tctgtgtctg tggggccatc tacactggcc tgttccttcc1380tgagaccaaa ggcaagacct tccaagagat ctccaaggaa ttacacagac tcaacttccc1440caggcgggcc cagggcccca cgtggaggag cctggaggtt atccagtcaa cagaactcta1500g1501<210>35<211>4077<212>DNA<213>人(Homo sapiens)<400>35atggtagtgg tgaagcccat gaacacaatg gctccggtgg tcacccggaa taccggtctt 60attctctatg agggtcagtc tcggcccctc acaggccctg caggcagtgg tccgcaaaac 120ttggtcatca gcgatgagga tgacctagaa gcagtgcggc tagaggtggt ggctgggctc 180cggcatggtc accttgtcat tctgggtgct tccagtggca gctctgctcc caagagcttt 240acagtggctg agctggcagc cggccaggtg gtctaccagc atgatgacag agacggctcg 300ctgagcgaca acctggtgct tcgcatggtg gatggaggag gcaggcacca ggtacagttt 360ctgttcccca tcaccttagt gcctgtggat gaccagccac ctgttctcaa tgccaacacg 420gggctgacac tggcagaggg tgaaacagtg cccatcctgc ccctttccct gagtgcaact 480gacatggatt cagatgattc tctgctgctt tttgtgctgg agtcaccctt cttaactacg 540gggcatctgc ttctccgcca aactcaccct ccccatgaga agcaggaact tctcagaggc 600ctttggagga aggagggggc attttatgag cgaacagtga cagagtggca gcagcaggac 660ataacagagg gcaggctgtt ctatagacac tctgggcccc atagtcctgg gccagtcaca 720gaccagttca catttagagt ccaggataac catgaccctc ctaatcagtc cgggctacag 780cggtttgtga ttcgtatcca tcctgtggat cgcctccctc cggagctggg cagtggctgt 840ccccttcgta tggtggtaca ggaatcccag ctcacaccac tgaggaagaa gtggctgcgc 900tacactgacc tggacacaga tgaccgagaa ctacgttaca cagtgactca gtcccccaca 960gacacagacg aaaatcacct gccagcccca ctgggtacct tggtcttgac tgacaacccc1020tcagtcgtgg tgacccattt tacccaagcc cagatcaacc atcataaaat tgcttacaga1080cccccgggtc aagaactggg cgtggctact cgagtggccc agttccagtt ccaggtggaa1140gaccgagctg ggaatgtggc tccaggtacc tttacccttt acttgcatcc cgtggacaac1200cagccacctg agatcctcaa caccggcttc actattcagg agaagggtca ccacatcctg1260agtgagacag agttgcacgt gaatgatgta gacactgatg ttgcccatat ctctttcact1320ctcactcagg cacccaaaca tggccacatg agagtgtctg gacagatcct gcatgtaggg1380ggtctcttcc acttggagga cataaaacag ggccgagttt cctatgccca taatggggac1440aagtccctga ctgatagctg ctccttggaa gtcagtgaca gacatcatgt ggtgcccatc1500actctcagag taaatgtccg gccagtggat gatgaagtgc ccatactgag ccatcctact1560ggcactctgg agtcctatct agatgtctta gaaaatgggg ctactgaaat cactgccaat1620gttattaagg ggaccaatga ggaaactgat gacttgatgt tgactttcct cttggaagat1680ccacctttgt atggggaaat cttggtcaat ggcattccag cagagcagtt tactcaaagg1740gacatcttgg agggctctgt tgtatatacc cacaccagtg gtgagatagg cctattgcct1800aaagcggatt cttttaacct gagtctgtca gatatgtctc aagaatggag aattggtggc1860aatactatcc aaggagttac tatatgggtg accatcctgc ctgttgatag ccaggcccca1920gaaatctttg taggtgaaca gttgatagta atggaaggtg ataaaagtgt tataacatca1980gtgcatataa gtgctgaaga tgtcgactcc ctgaatgatg acatcttgtg cactatagtt2040attcagccta cttcaggtta tgttgaaaac atttctccag caccaggctc tgagaaatca2100agagcaggga ttgccataag tgctttcaac ttgaaagatc tcaggcaggg ccacataaac2160tatgtccaga gtgtccataa aggggtggaa cctgtggagg accgatttgt atttcgttgt2220tctgatggca ttaacttttc agagagacag ttcttcccca ttgtaatcat tcccaccaat2280gatgaacagc cagagatgtt tatgagagaa tttatggtga tggaaggcat gagtctggta2340attgatacac ccattctcaa tgctgctgat gctgatgttc ccctggatga tttaactttc2400actattaccc aattccccac tcatggtcac atcatgaatc agctgataaa tggcacggtt2460ttggtcgaaa gcttcacctt ggatcagatc atagagagtt ccagcattat ttatgagcat2520gatgactccg agacccagga agacagtttt gtgattaaac taacagatgg gaagcactct2580gtggaaaaga cggtcctcat tatagttatc cctgttgatg atgagacgcc cagaatgact2640atcaataatg gactagaaat agaaattggg gataccaaga ttatcaacaa caaaatatta2700atggcaacag atttagattc agaagacaaa tctttggttt atattattcg ttatgggcca2760ggacatggct tattacagag acgaaaacct actggtgcct ttgaaaatat cacactgggc2820atgaatttta cccaggatga agtagacaga aacttaattc agtatgtcca tttggggcaa2880gagggcattc gggacctaat taaatttgat gtgactgatg gaataaatcc cctcatagat2940cgttactttt atgtgtccat cgggagcatt gacattgtct tccctgatgt gataagtaag3000ggagtgtcct tgaaagaagg tggcaaagtc actcttacaa cagacctact aagcactagt3060gacttgaaca gtcctgatga aaacttggtt tttaccatca ccagggctcc catgcgaggt3120cacctggaat gcacggatca gcctggtgtg tccatcacgt ctttcactca gctgcaactg3180gctggaaaca aaatctacta catccacaca gctgatgatg aagtgaaaat ggacagtttt3240gagtttcaag tcaccgatgg acgtaaccct gtctttcgga cattccgtat ctccattagc3300gatgtggaca ataaaaagcc agtggtcacc atccacaagc tggttgtcag tgaaagtgaa3360aacaagctga ttactccttt tgagctcact gtcgaagaca gagatactcc tgacaagctc3420ctgaaattca ctatcaccca ggtgcctatt catggccatc tcctattcaa caataccaga3480cctgtcatgg tttttaccaa gcaagacttg aatgaaaact taatcagcta caaacatgat3540ggcactgagt caagtgaaga tagcttctcc ttcacagtga ctgatggcac ccatacagac3600ttctatgttt ttcctgatac ggtgtttgaa acaaggagac cccaagtgat gaagatccag3660gtcttggctg ttgacaacag tgtcccccaa atcgcagtga ataagggggc ctctacactt3720cgcactctag ccactggcca cttggggttc atgatcacaa gcaaaatatt gaaagtggag3780gacagagaca gcttacacat ttctcttaga tttatcgtga cagaggcccc tcaacatgga3840tatcttctca acctggacaa aggcaaccac agcatcactc agttcacaca agctgacatt3900gatgacatga aaatatgcta tgtcttaaga gaaggggcta atgccacaag tgatatgttc3960tattttgcag ttgaagatgg tggtaagtat tcccctctcc tggtagtgac cgcaaggaga4020gacgcttttc ttggttgctc tctgatgaca ttattacaag aagtcttcat caagtaa 4077<210>36<211>9318<212>DNA<213>人(Homo sapiens)<400>36atggcacgat cttggctcac tgcaacctcc acctcccggc ccgctgcctt cggcagggcg 60ttgctgtccc ctggtctcgc gggggctgca ggggtccctg ctgaggaggc catagtgctg 120gcgaaccgcg gactccgggt gcctttcggc cgtgaagtct ggctggatcc cctgcatgac 180ctggtgttgc aggtgcagcc cggggaccgc tgcgcggttt cggtactaga caacgacgca 240ctggcccagc gaccgggccg cctgagtccc aagcgcttcc cgtgcgactt tggccctggc 300gaggtgcgct actctcacct gggcgcgcgc agcccgtctc gggaccgcgt ccggctgcag 360ctgcgctatg acgcgcccgg aggggcagta gtgctaccac tggtactgga ggtggaggtg 420gtcttcaccc agctggaggt tgtgactcgg aacttgcctc tggtcgtgga agaactgctg 480gggaccagca atgccctgga cgcgcggagc ctggagttcg ccttccagcc cgagacagag 540gagtgccgcg tgggcatcct gtccggcttg ggcgcgctgc ctcgctatgg agaactcctc 600cactacccgc aggtccctgg aggagccaga gagggaggcg ccccggagac tctcctgatg 660gactgcaaag ctttccagga actaggcgtg cgctatcgcc acacagccgc cagtcgctca 720ccaaacaggg actggatacc catggtggtg gagctgcgtt cacgaggggc tcctgtgggc 780agccctgctt tgaaacgcga gcacttccag gttctggtga ggatccgagg aggggccgag 840aacactgcac ccaagcccag tttcgtggcc atgatgatga tggaggtgga ccagtttgta 900ctgacggccc tgaccccaga catgctggca gccgaggatg ctgagtctcc ctctgacctg 960ttgatcttca accttacttc tccattccag cctggccagg gctacttggt gagcaccgat1020gatcgcagcc tgcccctttc ctccttcact cagagggatc tgcggctcct gaagattgcc1080taccagcccc cttctgaaga ctctgaccag gagcgcctct ttgaactgga attggaggta1140gtggatctag aaggagcagc ttcagaccct tttgccttca tggtagtggt gaagcccatg1200aacacaatgg ctccggtggt cacccggaat accggtctta ttctctatga gggtcagtct1260cggcccctca caggccctgc aggcagtggt ccgcaaaact tggtcatcag cgatgaggat1320gacctagaag cagtgcggct agaggtggtg gctgggctcc ggcatggtca ccttgtcatt1380ctgggtgctt ccagtggcag ctctgctccc aagagcttta cagtggctga gctggcagcc1440ggccaggtgg tctaccagca tgatgacaga gacggctcgc tgagcgacaa cctggtgctt1500cgcatggtgg atggaggagg caggcaccag gtacagtttc tgttccccat caccttagtg1560cctgtggatg accagccacc tgttctcaat gccaacacgg ggctgacact ggcagagggt1620gaaacagtgc ccatcctgcc cctttccctg agtgcaactg acatggattc agatgattct1680ctgctgcttt ttgtgctgga gtcacccttc ttaactacgg ggcatctgct tctccgccaa1740actcaccctc cccatgagaa gcaggaactt ctcagaggcc tttggaggaa ggagggggca1800ttttatgagc gaacagtgac agagtggcag cagcaggaca taacagaggg caggctgttc1860tatagacact ctgggcccca tagtcctggg ccagtcacag accagttcac atttagagtc1920caggataacc atgaccctcc taatcagtcc gggctacagc ggtttgtgat tcgtatccat1980cctgtggatc gcctccctcc ggagctgggc agtggctgtc cccttcgtat ggtggtacag2040gaatcccagc tcacaccact gaggaagaag tggctgcgct acactgacct ggacacagat2100gaccgagaac tacgttacac agtgactcag ccccccacag acacagacga aaatcacctg2160ccagccccac tgggtacctt ggtcttgact gacaacccct cagtcgtggt gacccatttt2220acccaagccc agatcaacca tcataaaatt gcttacagac ccccgggtca agaactgggc2280gtggctactc gagtggccca gttccagttc caggtggaag accgagctgg gaatgtggct2340ccaggtacct ttacccttta cttgcatccc gtggacaacc agccacctga gatcctcaac2400accggcttca ctattcagga gaagggtcac cacatcctga gtgagacaga gttgcacgtg2460aatgatgtag acactgatgt tgcccatatc tctttcactc tcactcaggc acccaaacat2520ggccacatga gagtgtctgg acagatcctg catgtagggg gtctcttcca cttggaggac2580ataaaacagg gccgagtttc ctatgcccat aatggggaca agtccctgac tgatagctgc2640tccttggaag tcagtgacag acatcatgtg gtgcccatca ctctcagagt aaatgtccgg2700ccagtggatg atgaagtgcc catactgagc catcctactg gcactctgga gtcctatcta2760gatgtcttag aaaatggggc tactgaaatc actgccaatg ttattaaggg gaccaatgag2820gaaactgatg acttgatgtt gactttcctc ttggaagatc cacctttgta tggggaaatc2880ttggtcaatg gcattccagc agagcagttt actcaaaggg acatcttgga gggctctgtt2940gtatataccc acaccagtgg tgagataggc ctattgccta aagcggattc ttttaacctg3000agtctgtcag ataagtctca agaatggaga attggtggca atactatcca aggagttact3060atatgggtga ccatcctgcc tgttgatagc caggccccag aaatctctgt aggtgaacag3120ttgatagtaa tggaaggtga taaaagtgtt ataacatcag tgcatataag tgctgaagat3180gtcgactccc tgaatgatga catcttgtgc actatagtta ttcagcctac ttcaggttat3240gttgaaaaca tttctccagc accaggctct gagaaatcaa gagcagggat tgccataagt3300gctttcaact tgaaagatct caggcagggc cacataaact atgtccagag tgtccataaa3360ggggtggaac ctgtggagga ccgatttgta tttcgttgtt ctgatggcat taacttttca3420gagagacagt tcttccccat tgtaatcatt cccaccaatg atgaacagcc agagatgttt3480atgagagaat ttatggtgat ggaaggcatg agtctggtaa ttgatacacc cattctcaat3540gctgctgatg ctgatgttcc cctggatgat ttaactttca ctattaccca attccccact3600catggtcaca tcatgaatca gctgataaat ggcacggttt tggtcgaaag cttcaccttg3660gatcagatca tagagagttc cagcattatt tatgagcatg atgactccga gacccaggaa3720gacagttttg tgattaaact aacagatggg aagcactctg tggaaaagac ggtcctcatt3780atagttatcc ctgttgatga tgagacgccc agaatgacta tcaataatgg actagaaata3840gaaattgggg ataccaagat tatcaacaac aaaatattaa tggcaacaga tttagattca3900gaagacaaat ctttggttta tattattcgt tatgggccag gacatggctt attacagaga3960cgaaaaccta ctggtgcctt tgaaaatatc acactgggca tgaattttac ccaggatgaa4020gtagacagaa acttaattca gtatgtccat ttggggcaag agggcattcg ggacctaatt4080aaatttgatg tgactgatgg aataaatccc ctcatagatc gttactttta tgtgtccatc4140gggagcattg acattgtctt ccctgatgtg ataagtaagg gagtgtcctt gaaagaaggt4200ggcaaagtca ctcttacaac agacctacta agcactagtg acttgaacag tcctgatgaa4260aacttggttt ttaccatcac cagggctccc atgcgaggtc acctggaatg cacggatcag4320cctggtgtgt ccatcacgtc tttcactcag ctgcaactgg ctggaaacaa aatctactac4380atccacacag ctgatgatga agtgaaaatg gacagttttg agtttcaagt caccgatgga4440cgtaaccctg tctttcggac attccgtatc tccattagcg atgtggacaa taaaaagcca4500gtggtcacca tccacaagct ggttgtcagt gaaagtgaaa acaagctgat tactcctttt4560gagctcactg tcgaagacag agatactcct gacaagctcc tgaaattcac tatcacccag4620gtgcctattc atggccatct cctattcaac aataccagac ctgtcatggt ttttaccaag4680caagacttga atgaaaactt aatcagctac aaacatgatg gcactgagtc aagtgaagat4740agcttctcct tcacagtgac tgatggcacc catacagact tctatgtttt tcctgatacg4800gtgtttgaaa caaggagacc ccaagtgatg aagatccagg tcttggctgt tgacaacagt4860gtcccccaaa tcgcagtgaa taagggggcc tctacacttc gcactctagc cactggccac4920ttggggttca tgatcacaag caaaatattg aaagtggagg acagagacag cttacacatt4980tctcttagat ttatcgtgac agaggcccct caacatggat atcttctcaa cctggacaaa5040ggcaaccaca gcatcactca gttcacacaa gctgacattg atgacatgaa aatatgctat5100gtcttaagag aaggggctaa tgccacaagt gatatgttct attttgcagt tgaagatggt5160ggtggaaaca agttaacgta ccagaatttt cgtctgaatt gggcatggat ctcctttgaa5220aaggaatatt acctggtcaa tgaggactcc aaatttctag atgttgttct taaacgtaga5280ggttacttgg gagaaacttc ttttataagt attggcacaa gagacagaac tgcagaaaaa5340gacaaagact tcaagggcaa agcacagaaa caagtgcagt tcaacccagg ccagaccagg5400gccacatggc gagtgcggat cctgagtgat ggggagcatg agcagtctga aacctttcag5460gtggtactct cagagcccgt gctggctgcc ttggaattcc ccacagtcgc cactgttgag5520atcgttgatc caggagatga gccaactgtg tttattcccc agtccaaata ctccgttgaa5580gaagatgttg gtgagctgtt cattcccatc aggaggagcg gagatgtgag ccaggagttg5640atggtggtct gttataccca acaaggaaca gcaactggaa ctgtgccgac ttccgtgttg5700tcttactctg attacatatc caggcctgag gaccacacca gtgttgtccg ctttgacaaa5760gatgaacggg agaaactgtg tcggatagtc ataattgatg actctttgta cgaggaggag5820gaaaccttcc atgtccttct gagcatgccc atggggggaa gaatcggatc agagttccca5880ggggctcaag ttacaatcgt tcctgacaaa gatgatggtc catctgattc caaatttaat5940gttgctgaga actacagttt actgcctttc acctgttttc aaggtagcat agccacggca6000gaggcagcca cccagggagg gggacgcagc accagacaag tagctgcagt caaaaaagac6060aaagacttca agggcaaagc acagaaacaa gtgcagttca acccaggcca gaccagggcc6120acatggcgag tgcggatcct gagtgatggg gagcatgagc agtctgaaac ctttcaggtg6180gtactctcag agcccgtgct ggctgccttg gaattcccca cagtcgccac tgttgagatc6240gttgatccag gagatgcatg cccatggggg gaagaatcgg atcagagttc ccaggggctc6300aagttacaat cgttcctgac aaagatgatg gtgagtacta atttacttga aaattctttt6360tcccgggaag atcaacatca ggaacaactt tctagacaga aaaaatggga atctaaaaca6420atgataatat acacatttat tttatgtgag acagaaaagc cctgcattct tgagctgatg6480gacgatgtgc tctatgagga ggtagaggag ctccgcctgg tactcggcac tccacaaagc6540aactctccct ttggggctgc agttggtgaa caaaatgaaa ctctcataag gatccgagat6600gatgctgata agactgttat taaatttgga gaaaccaaat ttagtgtcac tgaacccaaa6660gaacctggag agtcggtggt tataagaatt ccagtgattc gccaaggaga cacttcaaag6720gtttccattg tgagagtcca caccaaggat ggctcggcca cctctggaga agactaccac6780cctgtgtcag aagaaattga gtttaaggaa ggggaaaccc agcacgtggt tgaaatcgaa6840gttacctttg acggggtgag agagatgaga gaggccttca ctgttcacct aaaacctgat6900gaaaatatga tagcagagat gcagctttcc aactttgagc tcaccctcag ccctgatggc6960acaagagttg gaaaccacaa gtgctccaac ctcctggatt atactgaagt gaagactcat7020tatggtttct tgactgatgc taccaaaaat ccagaaataa ttggagagac atatccttac7080cagtacagct tgtccatcag aggttccact accttgcgct tctaccggaa cctgaaccta7140gaggcctgtt tatgggagtt cgttagctac tatgacatgt cagaactcct tgctgactgc7200agatcagtgt tgaatgcaag catatttcat gagatggcac ctgaaggaaa gcaaagtaaa7260tgcttggtaa attctacttt atactctatt ttggaatgtc atgagagcct tccaaacttt7320tgcatttcag cattaaggat gggaaaatgg agaaaaataa aaagcaaacc atcagcacag7380actccatgtg ctcagaggct tcgtggtttt attgaccacc ccaggaaaca gcccctgcag7440caagccagtg ctgacccagg catgctcccc gtgatctcca ctagagagct ttccaacttt7500gagctcaccc tcagccctga tggcacaaga gttggaaacc acaagtgctc caacctcctg7560gattatactg aagtgaagac tcattatggt ttcttgactg atgctaccaa aaatccagaa7620ataattggag agacatatcc ttaccagtac agcttgtcca tcagaggttc cactaccttg7680cgcttctacc ggaacctgaa cctagaggcc tgtttatggg agttcgttag ctactatgac7740atgtcagaac tccttgctga ctgtggtggc accattggaa cagatggaca ggtcctaaac7800ctagtgcagt cctatgtgac ccttcgagtc cctctgtatg tttcctacgt gttccattcc7860cccgtggggg taggaggctg gcagcatttt gacttgaagt cagagcttcg tctaactttt7920gtgtacgaca ccgccatctt gtggaatgat ggaattggca gccccccaga ggctgaactt7980caaggttctc tctatccaac cagcatgcgc atcggtgatg aggggcgctt ggccgtgcac8040ttcaagacag aggctcagtt ccatggctta tttgtgctgt cacatcccgc atcctttaca8100agctcagtga tcatgtcagc tgatcatcca ggcctgacat tttccctccg cctcataagg8160agtgaaccaa cctataacca gccagtacag cagtggagct ttgtctctga ctttgccgta8220cgtgactact cagggaccta tactgtgaag ctggtgccat gcactgcccc atcacatcag8280gaataccgcc tgccagtcac ctgcaacccc agagaacctg tcacctttga ccttgacatc8340cgattccaac aggtcagtga tccagtggct gctgagttta gcttgaacac ccaaatgtac8400ctgctctcta agaagagtct ctggttgtct gatggatcca tgggattcgg gcaagagagt8460gatgttgctt ttgcagaagg tgatataatt tatggtcgtg tcatggtgga tcctgtccag8520aatctgggtg actcctttta ctgcagcatt gagaaggtgt ttctatgcac tggagctgat8580ggctatgttc ccaagtatag tccaatgaat gcagaatatg gctgcttagc cgactctcct8640tcactcttat atagatttaa aattgtggac aaagctcagc cagagacaca agcgaccagt8700tttggaaatg tcctatttaa tgccaaacta gcagtggatg accctgaagc cattctctta8760gtgaatcagc ctggatctga tggatttaaa gtcgactcaa caccactctt tcaggtcgct8820ctaggccgag aatggtatat acatacgatc tatacagtga gatcgaaaga caatgccaat8880cgaggtattg gcaaaagaag tgtggagtac cattctctgg tgagtcaagg aaagccccaa8940tccaccacca agagccggaa gaagagagag atcaggagca caccctcact ggcatgggag9000attggtgctg aaaacagtcg aggaacaaac atccagcaca ttgccctgga ccgcaccaag9060aggcagatcc cccatgggag agcacctcca gatggcatcc tcccctggga gctcaacagc9120cccagctctg cagtcagcct ggtcactgtg gtgggaggca ccacggtagg gttactcacc9180atctgcctca ctgtcattgc agtgctgatg tgcaggggca aggaaagttt cagggggaag9240gatgccccga aaggctccag cagcagtgag cccatggtgc ccccacagag ccatcacaat9300gacagctcag aagtttga 9318<210>37<211>1374<212>DNA<213>人(Homo sapiens)<400>37atggggtgta gtggagcctg gggcttgagc tgcccttgtc cacagacgcc atcctgggcc 60tggaggaaga tgcggacgcc atccatgagg aaccggagtg gcgccgtgtg gagcagggcc 120tctgtcccct tctctgcctg ggaagtagag gtgcagatga gggtgacggg actggggcgc 180cggggagccc agggcatggc cgtgtggtac acccggggca ggggccatgt aggctctgtc 240cttggggggc tggcttcgtg ggacggcatc gggatcttct ttgactctcc ggcagaggat 300actcaggaca gtcctgccat ccgtgtgctg gccagcgacg ggcacatccc ctctgagcag 360cctggggatg gagctagcca agggctgggc tcctgtcatt gggacttccg gaaccggcca 420caccccttca gagcacggat cacctactgg gggcagaggc tgcgcatgtc cttgaacagt 480ggcctcactc ccagtgatcc aggtgagttc tgtgtggatg tggggcccct gcttttggtc 540cctggaggtt tctttggggt ctcagcagcc accggcaccc tggcagatga tcatgatgtc 600ctgtccttcc tgaccttcag cctgagtgag cccagcccag aggttccccc tcagcccttc 660ctggagatgc agcacgtccg cctggcgagg cagctggaag ggctgtgggc aaggctgggc 720ttgggcacca gggaggatgt aactccaaaa tcagactctg aagctcaagg agaaggggaa 780aggctctttg acctggagga gacgctgggc agacaccgcc ggatcctgca ggctctgcgg 840ggtctctcca agcagctggc ccaggctgag agacaatgga agaagcagct gggcccccag 900gccaagccag gcctgacgga ggctggggat gcagctgtcc gcatggctgc agaagcccag 960gtctcctacc tgcctgtggg cattgagcat catttcttag agctggacca catcctgggc1020ctcctgcagg aggagcttcg gggcccggcg aaggcagcag ccaaggcccc ccgcccacct1080ggccagcccc caagggcctc ctcgtgcctg cagcctggca tcttcctgtt ctacctcctc1140attcagactg taggcttctt cggctacgtg cacttcaggc gcccggtgcc ccggccggcg1200aagaccatgg cgttcatggt gaagaccatg gtgggcggcc agctgaagaa cctcactggg1260agcctgggag gcggcgagga taagggagat ggggacaagt cggcagccga agctcagggc1320atgagccggg aggagtacga ggagtatcag aagcaactcg tggaagagaa gtga 1374<210>38<211>1581<212>DNA<213>人(Homo sapiens)<400>38atgccggcgg tcagtggtcc aggtccctta ttctgccttc tcctcctgct cctggacccc 60cacagccctg agacggggtg tcctcctcta cgcaggtttg agtacaagct cagcttcaaa 120ggcccaaggc tggcattgcc tggggctgga atacccttct ggagccatca tggagacgcc 180atcctgggcc tggaggaagt gcggctgacg ccatccatga ggaaccggag tggcgccgtg 240tggagcaggg cctctgtccc cttctctgcc tgggaagtag aggtgcagat gagggtgacg 300ggactggggc gccggggagc ccagggcatg gccgtgtggt acacccgggg caggggccat 360gtaggctctg tccttggggg gctggcttcg tgggacggca tcgggatctt ctttgactct 420ccggcagagg atactcagga cagtcctgcc atccgtgtgc tggccagcga cgggcacatc 480ccctctgagc agcctgggga tggagctagc caagggctgg gctcctgtca ttgggacttc 540cggaaccggc cacacccctt cagagcacgg atcacctact gggggcagag gctgcgcatg 600tccttgaaca gtggcctcac tcccagtgat ccaggtgagt tctgtgtgga tgtggggccc 660ctgcttttgg tccctggagg tttctttggg gtctcagcag ccaccggcac cctggcagat 720gatcatgatg tcctgtcctt cctgaccttc agcctgagtg agcccagccc agaggttccc 780cctcagccct tcctggagat gcagcacgtc cgcctggcga ggcagctgga agggctgtgg 840gcaaggctgg gcttgggcac cagggaggat gtaactccaa aatcagactc tgaagctcaa 900ggagaagggg aaaggctctt tgacctggag gagacgctgg gcagacaccg ccggatcctg 960caggctctgc ggggtctctc caagcagctg gcccaggctg agagacaatg gaagaagcag1020ctggggcccc caggccaagc caggcctgac ggaggctggg ccctggatgc ttcctgccag1080attccatcca ccccagggag gggtggccac ctctccatgt cactcaataa ggactctgcc1140aaggtcggtg ccctgctcca tggacagtgg actctgctcc aggccctgca agagatgagg1200gatgcagctg tccgcatggc tgcagaagcc caggtctcct acctgcctgt gggcattgag1260catcatttct tagagctgga ccacatcctg ggcctcctgc aggaggagct tcggggcccg1320gcgaaggcag cagccaaggc cccccgccca cctggccagc ccccaagggc ctcctcgtgc1380ctgcagcctg gcatcttcct gttctacctc ctcattcaga ctgtaggctt cttcggctac1440gtgcacttca ggcaggagct gaacaagagc cttcaggagt gtctgtccac aggcagcctt1500cctctgggtc ctgcaccaca cacccccagg gccctgggga ttctgaggag gcagcctctc1560cctgccagca tgcctgcctg a 1581<210>39<211>2715<212>DNA<213>人(Homo sapiens)<400>39atgctcttgg ctctatgttc atctctggct cttatttttg cagctcctgt cagtggacag 60cttgagcatt cagggaacta ctactgcaca gctgacaatg gctttggccc ccagcacagt 120gaggtggtga gtctctctgt cactgtccct gtgtctcatc ctgtcctcac cctcagctct 180gctgaggccc tgacttttga aggagccact gtgacacttc actcttcgct gatcctgcaa 240gctccacttt ctgtgtttga aggagacttc gtggttctga ggtgccgggc aaaggcggaa 300gtaacactga atactatgta caagaatggt aacgtcctga cattccttaa taaaagctct 360gacttccata ttcatcacgc aagtctcaaa gacaatggtg catatcactt tactggattt 420aacggaagta atttctctgt ttcttccaac atagtcaaaa tccaagtcca agagcatctc 480ctgccccagt ggttcctgaa ggcacctgat cccactgtgg cccttagtga gatattctca 540gtcaatagag gtccacttct gacaggcaca ggctcccgag ttatgactcc ctggatttac 600ttccctactg aggactggaa cttcactctt attcccatta ctgtggacga tgcttgcaaa 660aggccttgtg ctcctcgggc tccttgggaa gttggaagtc taacaccagg aaagagtttc 720cagcagaagg ggaacccaga cctgctcatg ggcccttttg atgttcttca cttgtccctc 780atcacacttt tttgcaacat ggcaggttct ttgttttatt atatggaact tggagaaaag 840aaagatgcat tatttgttac aggaaatgaa agcagaagct atcattggtt ccagaagttc 900agccttgctg gtgggcaaga agcagatcaa aagttgtggt ttccccctgg actgatgagt 960caggatattt tcatatatat cagacaaggt gagagttgtc ttgtgattga gatgtttcat1020caggtctaca gacggcctgc tggaggtgtt ccagtagagc atatgagtgt atgggctctc1080agggtgaata gttcgggact cttcgcctac gctgatggct ggctctttac tctctttcag1140ctccagtctg tggacaatct gagcccatca actcagtctc aaacacacga aggccatgaa1200aagttatgtc ccttcctggc catagggcca cctgcacata gcaggggcag cttcctcaga1260gcaaagaaga gtctagttgc atacatcaaa ggaaatcaac tctccttccc tccagtagaa1320gacctattgc ctaagtccca atggccctgc atccaggtgc ttcccaggaa tatagctgca1380gctgcacaca aacctgtgat ttccgtccat cctccatgga ccacattctt caaaggagag1440agagtgactc tgacttgcaa tggatttcag ttctatgcaa cagagaaaac aacatggtat1500catcggcact actggggaga aaagttgacc ctgaccccag gaaacaccct cgaggttcgg1560gaatctggac tgtacagatg ccaggcccgg ggctccccac gaagtaaccc tgtgcgcttg1620ctcttttctt caggtgagaa agaagactgt gtctctgaca agaatcctgc tacaaatcac1680actccaatgt ccaggaagag atcctcatgt agttctctaa gtgccacttc tttcatagct1740cctgctctga gactcgactc cttaatcctg caggcaccat attctgtgtt tgaaggtgac1800acattggttc tgagatgcca cagaagaagg aaagagaaat tgactgctgt gaaatatact1860tggaatggaa acattctttc catttctaat aaaagctggg atcttcttat cccacaagca1920agttcaaata acaatggcaa ttatcgatgc attggatatg gagacgagaa tgatgtattt1980agatcaaatt tcaaaataat taaaattcaa gggatccctg tgtctggggt gctcctggag2040acccagccct cagggggcca ggctgttgaa ggggagatgc tggtccttgt ctgctccgtg2100gctgaaggca caggggatac cacattctcc tggcaccgag aggacatgca ggagagtctg2160gggaggaaaa ctcagcgttc cctgagagca gagctggagc tccctgccat cagacagagc2220catgcagggg gatactactg tacagcagac aacagctacg gccctgtcca gagcatggtg2280ctgaatgtca ctgtgagaga gaccccaggc aacagagatg gccttgtcgc cgcgggagcc2340actggagggc tgctcagtgc tcttctcctg gctgtggccc tgctgtttca ctgctggcgt2400cggaggaagt cagtacaccc caaaaaggga gatttggtat actctgagat ccagactact2460cagctgggag aagaagagga aggaaatcat ggcaataaaa atcaagaact agaacttgtt2520aatgtaggag agagtttttc tcacagggca tgcatatgga gtactctaat gggaacttgc2580caaacaatcg ggggtgctaa tacctccagg acacttctag aggataagga tgtctcagtt2640gtctactctg aggtaaagac acaacaccca gataactcag ctggaaagat cagctctaag2700gatgaagaaa gttaa 2715<210>40<211>1548<212>DNA<213>人(Homo sapiens)<400>40atgctgctgt gggcgtcctt gctggccttt gctccagtct gtggacaatc tgcagctgca 60cacaaacctg tgatttccgt ccatcctcca tggaccacat tcttcaaagg agagagagtg 120actctgactt gcaatggatt tcagttctat gcaacagaga aaacaacatg gtatcatcgg 180cactactggg gagaaaagtt gaccctgacc ccaggaaaca ccctcgaggt tcgggaatct 240ggactgtaca gatgccaggc ccggggctcc ccacgaagta accctgtgcg cttgctcttt 300tcttcagact ccttaatcct gcaggcacca tattctgtgt ttgaaggtga cacattggtt 360ctgagatgcc acagaagaag gaaagagaaa ttgactgctg tgaaatatac ttggaatgga 420aacattcttt ccatttctaa taaaagctgg gatcttctta tcccacaagc aagttcaaat 480aacaatggca attatcgatg cattggatat ggagatgaga atgatgtatt tagatcaaat 540ttcaaaataa ttaaaattca agaactattt ccacatccag agctgaaagc tacagactct 600cagcctacag aggggaattc tgtaaacctg agctgtgaaa cacagcttcc tccagagcgg 660tcagacaccc cacttcactt caacttcttc agagatggcg aggtcatcct gtcagactgg 720agcacgtacc cggaactcca gctcccaacc gtctggagag aaaactcagg atcctattgg 780tgtggtgctg aaacagtgag gggtaacatc cacaagcaca gtccctcgct acagatccat 840gtgcagcgga tccctgtgtc tggggtgctc ctggagaccc agccctcagg gggccaggct 900gttgaagggg agatgctggt ccttgtctgc tccgtggctg aaggcacagg ggataccaca 960ttctcctggc accgagagga catgcaggag agtctgggga ggaaaactca gcgttccctg1020agagcagagc tggagctccc tgccatcaga cagagccatg cagggggata ctactgtaca1080gcagacaaca gctacggccc tgtccagagc atggtgctga atgtcactgt gagagagacc1140ccaggcaaca gagatggcct tgtcgccgcg ggagccactg gagggctgct cagtgctctt1200ctcctggctg tggccctgct gtttcactgc tggcgtcgga ggaagtcagg agttggtttc1260ttgggagacg aaaccaggct ccctcccgct ccaggcccag gagagtcctc ccattccatc1320tgccctgccc aggtggagct tcagtcgttg tatgttgatg tacaccccaa aaagggagat1380ttggtatact ctgagatcca gactactcag ctgggagaag aagaggaagc taatacctcc1440aggacacttc tagaggataa ggatgtctca gttgtctact ctgaggtaaa gacacaacac1500ccagataact cagctggaaa gatcagctct aaggatgaag aaagttaa 1548<210>41<211>2494<212>DNA<213>人(Homo sapiens)<400>41batggctgtg ggaggaggac acaaaggagt tagatgtcct ccctctgctc gcagctccca 60ggtgcccacg tgctgcgctg gctggaggca gcaaggggac gagtgtggga ttgcggtgtg 120cgaaggcaac tccacgtgct cagagaacga ggtgtgcgtg aggcctggcg agtgccgctg 180ccgccacggc tacttcggtg ccaactgcga caccaagtgc ccgcgccagt tctggggccc 240cgactgcaag gagctgtgta gctgccaccc acacgggcag tgcgaggacg tgacaggcca 300gtgtacttgt cacgcgcggc gctggggcgc gcgctgcgag catgcgtgcc agtgccagca 360cggcacgtgc cacccccgga gcggcgcgtg ccgctgtgag tccggctggt ggggcgcgca 420gtgcgccagc gcgtgctact gcagcgccac gtcgcgctgc gacccacaga ccggcgcctg 480cctgtgccac gcaggctggt ggggccgcag ctgcaacaac cagtgcgcct gcaactcgtc 540tccctgcgag cagcagagcg gccgctgtca gtgccgcgag cgtacgttcg gcgcgcgctg 600cgatcgctac tgccagtgct tccgcggccg ctgccaccct gtggacggca cgtgtgcctg 660cgagccgggc taccgcggca agtactgtcg cgagccgtgc cccgccggct tctacggctt 720gggctgtcgc cgccggtgtg gccagtgcaa gggccagcag ccgtgcacgg tggccgaggg 780ccgctgcttg acgtgcgagc ccggctggaa cggaaccaag tgcgaccagc cttgcgccac 840cggtttctat ggcgagggct gcagccaccg ctgtccgcca tgccgcgacg ggcatgcctg 900taaccatgtc accggcaagt gtacgcgctg caacgcgggc tggatcggcg accggtgcga 960gaccaagtgt agcaatggca cttacggcga ggactgcgcc ttcgtgtgcg ccgactgcgg1020cagcggacac tgcgacttcc agtcggggcg ctgcctgtgc agccctggcg tccacgggcc1080ccactgtaac gtgacgtgcc cgcccggact ccacggcgcg gactgtgctc aggcctgcag1140ctgccacgag gacacgtgcg acccggtcac tggtgcctgc cacctagaaa ccaaccagcg1200caagggcgtg atgggcgcgg gcgcgctgct cgtcctgctc gtctgcctgc tgctctcgct1260gctcggctgc tgctgcgctt gccgcggcaa ggaccctacg cgccgacccc gcccccgcag1320ggagctttcg cttgggagga agaaggcgcc gcaccgacta tgcgggcgct tcagtcgcat1380cagcatgaag ctgccccgga tcccgctccg gaggcagaaa ctacccaaag tcgtagtggc1440ccaccacgac ctggataaca cactcaactg cagcttcctg gagccaccct cagggctgga1500gcagccctca ccatcctggt cctctcgggc ctccttctcc tcgtttgaca ccactgatga1560aggccctgtg tactgtgtac cccatgagga ggcaccagcg gagagccggg accccgaagt1620ccccactgtc cctgccgagg cgccggcgcc gtcccctgtg cccttgacca cgccagcctc1680cgccgaggag gcgatacccc tccccgcgtc ctccgacagc gagcggtcgg cgtccagcgt1740ggaggggccc ggaggggctc tgtacgcgcg cgtggcccga cgcgaggccc ggccggcccg1800ggcccggggc gagattgggg gcctgtcgct gtcgccatcg cccgagcgca ggaaaccgcc1860gccacctgac cccgccacca agcctaaggt gtcctggatc cacggcaagc acagcgccgc1920tgcagctggc cgtgcgccct caccaccgcc gccaggctcc gaggccgcgc ccagccccag1980caagaggaaa cggacgccca gcgacaaatc ggcgcatacg gtcgaacacg gcagcccccg2040gacccgcgac ccaacgccgc gccccccggg gctgcccgag gaggcgacag ccctcgctgc2100gccctcgccg cccagggccc gagcgcgcgc cgcgccccgg cctcttggag cccacggacg2160ccggcggtcc cccgcgaagc gcgccgaggc tgcctccatg ttggccgctg acgtgcgcgg2220caagactcgc agcctgggcc gcgccgaggt ggccctgggc gcgcagggcc ccagggaaaa2280gccggcgccc ccacagaaag ccaagcgctc cgtgccgcca gcctcgcccg cccgcgcgcc2340cccagcgacc gaaaccccgg ggcctgagaa ggcggcgacc gacttgcccg cgcctgagac2400cccccggaag aagaccccca tccagaagcc gccgcgcaag aagagccggg aggcggcggg2460cgagctgggc agggcgggcg cacccaccct gtag2494<210>42<211>2614<212>DNA<213>人(Homo sapiens)<400>42batggagggc gcagggcccc ggggggccgg gccggcgcgg cgccggggag ccggggggcc 60gccgtcaccg ctgctgccgt cgctgctgct gctgctgctg ctctggatgc tgccggacac 120cgtggcgcct caggaactga accctcgcgg ccgcaacgtg tgccgtgctc ccggctccca 180ggtgcccacg tgctgcgctg gctggaggca gcaaggggac gagtgtggga ttgcggtgtg 240cgaaggcaac tccacgtgct cagagaacga ggtgtgcgtg aggcctggcg agtgccgctg 300ccgccacggc tacttcggtg ccaactgcga caccaagtgc ccgcgccagt tctggggccc 360cgactgcaag gagctgtgta gctgccaccc acacgggcag tgcgaggacg tgacaggcca 420gtgtacttgt cacgcgcggc gctggggcgc gcgctgcgag catgcgtgcc agtgccagca 480cggcacgtgc cacccccgga gcggcgcgtg ccgctgtgag tccggctggt ggggcgcgca 540gtgcgccagc gcgtgctact gcagcgccac gtcgcgctgc gacccacaga ccggcgcctg 600cctgtgccac gcaggctggt ggggccgcag ctgcaacaac cagtgcgcct gcaactcgtc 660tccctgcgag cagcagagcg gccgctgtca gtgccgcgag cgtacgttcg gcgcgcgctg 720cgatcgctac tgccagtgct tccgcggccg ctgccaccct gtggacggca cgtgtgcctg 780cgagccgggc taccgcggca agtactgtcg cgagccgtgc cccgccggct tctacggctt 840gggctgtcgc cgccggtgtg gccagtgcaa gggccagcag ccgtgcacgg tggccgaggg 900ccgctgcttg acgtgcgagc ccggctggaa cggaaccaag tgcgaccagc cttgcgccac 960cggtttctat ggcgagggct gcagccaccg ctgtccgcca tgccgcgacg ggcatgcctg1020taaccatgtc accggcaagt gtacgcgctg caacgcgggc tggatcggcg accggtgcga1080gaccaagtgt agcaatggca cttacggcga ggactgcgcc ttcgtgtgcg ccgactgcgg1140cagcggacac tgcgacttcc agtcggggcg ctgcctgtgc agccctggcg tccacgggcc1200ccactgtaac gtgacgtgcc cgcccggact ccacggcgcg gactgtgctc aggcctgcag1260ctgccacgag gacacgtgcg acccggtcac tggtgcctgc cacctagaaa ccaaccagcg1320caagggcgtg atgggcgcgg gcgcgctgct cgtcctgctc gtctgcctgc tgctctcgct1380gctcggctgc tgctgcgctt gccgcggcaa ggaccctacg cgccgacccc gcccccgcag1440ggagctttcg cttgggagga agaaggcgcc gcaccgacta tgcgggcgct tcagtcgcat1500cagcatgaag ctgccccgga tcccgctccg gaggcagaaa ctacccaaag tcgtagtggc1560ccaccacgac ctggataaca cactcaactg cagcttcctg gagccaccct cagggctgga1620gcagccctca ccatcctggt cctctcgggc ctccttctcc tcgtttgaca ccactgatga1680aggccctgtg tactgtgtac cccatgagga ggcaccagcg gagagccggg accccgaagt1740ccccactgtc cctgccgagg cgccggcgcc gtcccctgtg cccttgacca cgccagcctc1800cgccgaggag gcgatacccc tccccgcgtc ctccgacagc gagcggtcgg cgtccagcgt1860ggaggggccc ggaggggctc tgtacgcgcg cgtggcccga cgcgaggccc ggccggcccg1920ggcccggggc gagattgggg gcctgtcgct gtcgccatcg cccgagcgca ggaaaccgcc1980gccacctgac cccgccacca agcctaaggt gtcctggatc cacggcaagc acagcgccgc2040tgcagctggc cgtgcgccct caccaccgcc gccaggctcc gaggccgcgc ccagccccag2100caagaggaaa cggacgccca gcgacaaatc ggcgcatacg gtcgaacacg gcagcccccg2160gacccgcgac ccaacgccgc gccccccggg gctgcccgag gaggcgacag ccctcgctgc2220gccctcgccg cccagggccc gagcgcgcgc cgcgccccgg cctcttggag cccacggacg2280ccggcggtcc cccgcgaagc gcgccgaggc tgcctccatg ttggccgctg acgtgcgcgg2340caagactcgc agcctgggcc gcgccgaggt ggccctgggc gcgcagggcc ccagggaaaa2400gccggcgccc ccacagaaag ccaagcgctc cgtgccgcca gcctcgcccg cccgcgcgcc2460cccagcgacc gaaaccccgg ggcctgagaa ggcggcgacc gacttgcccg cgcctgagac2520cccccggaag aagaccccca tccagaagcc gccgcgcaag aagagccggg aggcggcggg2580cgagctgggc agggcgggcg cacccaccct gtag 2614<210>43<211>402<212>DNA<213>人(Homo sapiens)<400>43atcgactgcc gcgcggagca gggccgtacg ccgctcatgg tggccgtggg gctgccggac 60cccgcgctgc gcgcgcgctt cgtgcggctg ctgctcgagc agggtgctgc agtgaacctg 120cgagacgagc gcggccgcac cgcactcagc ctggcgtgcg agcgaggcca cctggacgcc 180gtgcagctgc tggtgcagtt cagcggtgac cccgaggcgg ccgactctgc gggcaacagc 240ccggtgatgt gggcggcggc ctgcggccac ggggcggtgc tcgagttcct ggtgcggtcc 300ttccgccgcc taggcctgcg cctcgaccgc accaaccgtg cggggctcac cgcgctgcaa 360ctggccgccg cccgcggcca cgggacctgt gtgcaggccc tc402<210>44<211>975<212>DNA<213>人(Homo sapiens)<400>44atgctcaaac ccaaggacct gtgcccccga gcggggacgc gcaccttcct ggaggccatg 60caggcgggca aagtgcactt ggcccgcttc gtgttggatg cgctggaccg cagcatcatc 120gactgccgcg cggagcaggg ccgtacgccg ctcatggtgg ccgtggggct gccggacccc 180gcgctgcgcg cgcgcttcgt gcggctgctg ctcgagcagg gtgctgcagt gaacctgcga 240gacgagcgcg gccgcaccgc actcagcctg gcgtgcgagc gaggccacct ggacgccgtg 300cagctgctgg tgcagttcag cggtgacccc gaggcggccg actctgcggg caacagcccg 360gtgatgtggg cggcggcctg cggccacggg gcggtgctcg agttcctggt gcggtccttc 420cgccgcctag gcctgcgcct cgaccgcacc aaccgtgcgg ggctcaccgc gctgcaactg 480gccgccgccc gcggccacgg gacctcggcg ggcggccacg gcggcgaggc tggctcagcg 540ggcaagaatt cgggccggca ccgggcgcag ggcagcgaac ggcccgagct gggtcggagc 600atgagcctgg ctctaggtgc ggtaaccgag gaggaggctg cccgcctgcg ggctggggcc 660ctgatggccc taccaaactc gccccagtct tcggggactg ggcggtggcg ctcacaggag 720gtgctggagg gagcgccccc aaccttagcg caagccccca ttggcctcag tccccacccg 780gagggcggcc ccggctctgg ccgcctgggt ttgcgccgac gctccacagc cccagatatc 840cccagcctgg tcggggaggc gccagggccc gagagtggcc cggagttaga ggccaacgct 900ctgtctgtct cggtgcctgg gccgaaccct tggcaggcgg gcaccgaggc tgtggtgctg 960cgtgctcagc ggtaa 975<210>45<211>568<212>PRT<213>人(Homo sapiens)<400>45Met Lys Glu Ala Glu Met Asp Gly Glu Ala Val Arg Phe Cys Thr Asp1 5 10 15Asn Gln Cys Val SeT Leu His Pro Gln Glu Val Asp Ser Val Ala Met20 25 30Ala Pro Ala Ala Pro Lys Ile Pro Arg Leu Val Gln Ala Thr Pro Ala35 40 45Phe Met Ala Val Thr Leu Val Phe Ser Leu Val Thr Leu Phe Val Val50 55 60Gly Lys Pro Pro Val Gln Gln Gln Thr Arg Pro Val Pro Lys Pro Val65 70 75 80Gln Ala Val Ile Leu Gly Asp Asn Ile Thr Gly His Leu Pro Phe Glu85 90 95Pro Asn Asn His His His Phe Gly Arg Glu Ala Glu Met Arg Glu Leu100 105 110Ile Gln Thr Phe Lys Gly His Met Glu Asn Ser Ser Ala Trp Val Val115 120 125Glu Ile Gln Met Leu Lys Cys Arg Val Asp Asn Val Asn Ser Gln Leu130 135 140Gln Val Leu Gly Asp His Leu Gly Asn Thr Asn Ala Asp Ile Gln Met145 150 155 160Val Lys Gly Val Leu Lys Asp Ala Thr Thr Leu Ser Leu Gln Thr Gln165 170 175Met Leu Arg Ser Ser Leu Glu Gly Thr Asn Ala Glu I1e Gln Arg Leu180 185 190Lys Glu Asp Leu Glu Lys Ala Asp Ala Leu Thr Phe Gln Thr Leu Asn195 200 205Phe Leu Lys Ser Ser Leu Glu Asn Thr Ser Ile Glu Leu His Val Leu210 215 220Ser Arg Gly Leu Glu Asn Ala Asn Ser Glu Ile Gln Met Leu Asn Ala225 230 235 240Arg Ala Asn Ala Glu Ile Gln Gly Leu Lys Glu Asn Leu Gln Asn Thr245 250 255Asn Ala Leu Asn Ser Gln Thr Gln Ala Phe Ile Lys Ser Ser Phe Asp260 265 270Asn Thr Ser Ala Glu Ile Gln Phe Leu Arg Gly His Leu Glu Arg Ala275 280 285Gly Asp Glu Ile His Val Leu Lys Arg Asp Leu Lys Met Val Thr Ala290 295 300Gln Thr Gln Lys Ala Asn Gly Arg Leu Asp Gln Thr Asp Thr Gln Ile305 310 315 320Gln Val Phe Lys Ser Glu Met Glu Asn Val Asn Thr Leu Asn Ala Gln325 330 335Ile Gln Val Leu Asn Gly His Met Lys Asn Ala Ser Arg Glu Ile Gln340 345 350Thr Leu Lys Gln Gly Met Lys Asn Ala Ser Ala Leu Thr Ser Gln Thr355 360 365Gln Met Leu Asp Ser Asn Leu Gln Lys Ala Ser Ala Glu Ile Gln Arg370 375 380Leu Arg Gly Asp Leu Glu Asn Thr Lys Ala Leu Thr Met Glu Ile Gln385 390 395 400Gln Glu Gln Ser Arg Leu Lys Thr Leu His Val Val Ile Thr Ser Gln405 410 415Glu Gln Leu Gln Arg Thr Gln Ser Gln Leu Leu Gln Met Val Leu Gln420 425 430Gly Trp Lys Phe Asn Gly Gly Ser Leu Tyr Tyr Phe Ser Ser Val Lys435 440 445Lys Ser Trp His Glu Ala Glu Gln Phe Cys Val Ser Gln Gly Ala His450 455 460Leu Ala Ser Val Ala Ser Lys Glu Glu Gln Ala Phe Leu Val Glu Phe465 470 475 480Thr Ser Lys Val Tyr Tyr Trp Ile Gly Leu Thr Asp Arg Gly Thr Glu485 490 495Gly Ser Trp Arg Trp Thr Asp Gly Thr Pro Phe Asn Ala Ala Gln Asn500 505 510Lys Ala Pro Val Val Phe Gly Phe Trp Glu Lys Asn Gln Ser Asp Asn515 520 525Trp Arg His Lys Asn Gly Gln Thr Glu Asp Cys Val Gln Ile Gln Gln530 535 540Lys Trp Asn Asp Met Thr Cys Asp Thr Pro Tyr Gln Trp Val Cys Lys545 550 555 560Lys Pro Met Gly Gln Gly Val Ala565<210>46<211>364<212>PRT<213>人(Homo sapiens)<400>46Met Ser Arg Gln Gly Lys Leu Phe Ser Ala Phe Gly Val Gly Cys Cys1 5 10 15Val Thr Ala Gly Leu Pro Lys Asp Asp Asn Thr Pro Ser Thr Ile Ala20 25 30Asp Val His Asn Gly Tyr Thr Met Asn Val Val Glu Gln Val Leu Lys35 40 45Asp Ser Phe Val Leu Phe Phe Pro Gly Thr Leu Cys Asp Phe Pro Lys50 55 60Ile His His Gly Phe Leu Tyr Asp Glu Glu Asp Tyr Asn Pro Phe Ser65 70 75 80Gln Val Pro Thr Gly Glu Val Phe Tyr Tyr Ser Cys Glu Tyr Asn Phe85 90 95Val Ser Pro Ser Lys Ser Phe Trp Thr Arg Ile Thr Cys Thr Glu Glu100 105 110Gly Trp Ser Pro Thr Pro Lys Cys Leu Arg Met Cys Ser Phe Pro Phe115 120 125Val Lys Asn Gly His Ser Glu Ser Ser Gly Leu Ile His Leu Glu Gly130 135 140Asp Thr Val Gln Ile Ile Cys Asn Thr Gly Tyr Ser Leu Gln Asn Asn145 150 155 160Glu Lys Asn Ile Ser Cys Val Glu Arg Gly Trp Ser Thr Pro Pro Ile165 170 175Cys Ser Phe Thr Met Lys Thr Cys Gly Tyr Ile Pro Glu Leu Glu Tyr180 185 190Gly Tyr Val Gln Pro Ser Val Pro Pro Tyr Gln His Gly Val Ser Val195 200 205Glu Val Asn Cys Arg Asn Glu Tyr Ala Met Ile Gly Asn Asn Met Ile210 215 220Thr Cys Ile Asn Gly Ile Trp Thr Glu Leu Pro Met Cys Val Glu Ser225 230 235 240Thr Ala Tyr Cys Gly Pro Pro Pro Ser Ile Asn Asn Gly Asp Thr Thr245 250 255Ser Phe Pro Leu Ser Val Tyr Pro Pro Gly Ser Thr Val Thr Tyr Arg260 265 270Cys Gln Ser Phe Tyr Lys Leu Gln Gly Ser Val Thr Val Thr Cys Arg275 280 285Asn Lys Gln Trp Ser Glu Pro Pro Arg Cys Leu Asp Pro Cys Val Val290 295 300Ser Glu Glu Asn Met Asn Lys Asn Asn Ile Gln Leu Lys Trp Arg Asn305 310 315 320Asp Gly Lys Leu Tyr Ala Lys Thr Gly Asp Ala Val Glu Phe Gln Cys325 330 335Lys Phe Pro His Lys Ala Met Ile Ser Ser Pro Pro Phe Arg Ala Ile340 345 350Cys Gln Glu Gly Lys Phe Glu Tyr Pro Ile Cys Glu355 360<210>47<211>327<212>PRT<213>人(Homo sapiens)<400>47Met Leu Leu Leu Phe Ser Val Ile Leu Ile Ser Trp Val Ser Thr Val1 5 10 15Gly Gly Glu Gly Thr Leu Cys Asp Phe Pro Lys Ile His His Gly Phe20 25 30Leu Tyr Asp Glu Glu Asp Tyr Asn Pro Phe Ser Gln Val Pro Thr Gly35 40 45Glu Val Phe Tyr Tyr Ser Cys Glu Tyr Asn Phe Val Ser Pro Ser Lys50 55 60Ser Phe Trp Thr Arg Ile Thr Cys Thr Glu Glu Gly Trp Ser Pro Thr65 70 75 80Pro Lys Cys Leu Arg Met Cys Ser Phe Pro Phe Val Lys Asn Gly His85 90 95Ser Glu Ser Ser Gly Leu Ile His Leu Glu Gly Asp Thr Val Gln Ile100 105 110lle Cys Asn Thr Gly Tyr Ser Leu Gln Asn Asn Glu Lys Asn Ile Ser115 120 125Cys Val Glu Arg Gly Trp Ser Thr Pro Pro Ile Cys Ser Phe Thr Met130 135 140Lys Thr Cys Gly Tyr Ile Pro Glu Leu Glu Tyr Gly Tyr Val Gln Pro145 150 155 160Ser Val Pro Pro Tyr Gln His Gly Val Ser Val Glu Val Asn Cys Arg165 170 175Asn Glu Tyr Ala Met Ile Gly Asn Asn Met Ile Thr Cys Ile Asn Gly180 185 190Ile Trp Thr Glu Leu Pro Met Cys Val Glu Ser Thr Ala Tyr Cys Gly195 200 205Pro Pro Pro Ser Ile Asn Asn Gly Asp Thr Thr Ser Phe Pro Leu Ser210 215 220Val Tyr Pro Pro Gly Ser Thr Val Thr Tyr Arg Cys Gln Ser Phe Tyr225 230 235 240Lys Leu Gln Gly Ser Val Thr Val Thr Cys Arg Asn Lys Gln Trp Ser245 250 255Glu Pro Pro Arg Cys Leu Asp Pro Cys Val Val Ser Glu Glu Asn Met260 265 270Asn Lys Asn Asn Ile Gln Leu Lys Trp Arg Asn Asp Gly Lys Leu Tyr275 280 285Ala Lys Thr Gly Asp Ala Val Glu Phe Gln Cys Lys Phe Pro His Lys290 295 300Ala Met Ile Ser Ser Pro Pro Phe Arg Ala Ile Cys Gln Glu Gly Lys305 310 315 320Phe Glu Tyr Pro Ile Cys Glu325<210>48<211>154<212>PRT<213>人(Homo sapiens)<400>48Met Ala Pro Ala Arg Ala Gly Cys Cys Pro Leu Leu Leu Leu Leu Leu1 5 10 15Gly Leu Trp Val Ala Glu Val Leu Val Arg Ala Lys Pro Lys Asp Met20 25 30Thr Ser Ser Gln Trp Phe Lys Thr Gln His Val Gln Pro Ser Pro Gln35 40 45Ala Cys Asn Ser Ala Met Ser Ile Ile Asn Lys Tyr Thr Glu Arg Cys50 55 60Lys Asp Leu Asn Thr Phe Leu His Glu Pro Phe Ser Ser Val Ala Ile65 70 75 80Thr Cys Gln Thr Pro Asn Ile Ala Cys Lys Asn Ser Cys Lys Asn Cys85 90 95His Gln Ser His Gly Pro Met Ser Leu Thr Met Gly Glu Leu Thr Ser100 105 110Gly Lys Tyr Pro Asn Cys Arg Tyr Lys Glu Lys His Leu Asn Thr Pro115 120 125Tyr Ile Val Ala Cys Asp Pro Pro Gln Gln Gly Asp Pro Gly Tyr Pro130 135 140Leu Val Pro Val His Leu Asp Lys Val Val145 150<210>49<211>502<212>PRT<213>人(Homo sapiens)<400>49Met Arg Gln Leu Gly Gly Ser Leu Arg Pro Pro Arg Ala Ala His Gly1 5 10 15Ala Glu Pro Leu Pro Ser Ala Leu Gly Pro Cys Ala Gly Gly Asp Arg20 25 30Asp Leu Gly Arg Gly Thr Pro Gly Trp Glu Pro Arg Arg Ala Arg Val35 40 45Pro Ile His Glu Gln Val Asp Pro Pro Arg Glu Gly Pro His Leu Phe50 55 60Gln Asn Leu Leu Leu Phe Leu Trp Ala Leu Leu Asn Cys Gly Leu Gly65 70 75 80Val Ser Ala Gln Gly Pro Gly Glu Trp Thr Pro Trp Val Ser Trp Thr85 90 95Arg Cys Ser Ser Ser Cys Gly Arg Gly Val Ser Val Arg Ser Arg Arg100 105 110Cys Leu Arg Leu Pro Gly Glu Glu Pro Cys Trp Gly Asp Ser His Glu115 120 125Tyr Arg Leu Cys Gln Leu Pro Asp Cys Pro Pro Gly Ala Val Pro Phe130 135 140Arg Asp Leu Gln Cys Ala Leu Tyr Asn Gly Arg Pro Val Leu Gly Thr145 150 155 160Gln Lys Thr Tyr Gln Trp Val Pro Phe His Gly Ala Pro Asn Gln Cys165 170 175Asp Leu Asn Cys Leu Ala Glu Gly His Ala Phe Tyr His Ser Phe Gly180 185 190Arg Val Leu Asp Gly Thr Ala Cys Ser Pro Gly Ala Gln Gly Val Cys195 200 205Val Ala Gly Arg Cys Leu Ser Ala Gly Cys Asp Gly Leu Leu Gly Ser210 215 220Gly Ala Leu Glu Asp Arg Cys Gly Arg Cys Gly Gly Ala Asn Asp Ser225 230 235 240Cys Leu Phe Val Gln Arg Val Phe Arg Asp Ala Gly Ala Phe Ala Gly245 250 255Tyr Trp Asn Val Thr Leu Ile Pro Glu Gly Ala Arg His Ile Arg Val260 265 270Glu His Arg Ser Arg Asn His Leu Gly Ile Leu Gly Ser Leu Met Gly275 280 285Gly Asp Gly Arg Tyr Val Leu Asn Gly His Trp Val Val Ser Pro Pro290 295 300Gly Thr Tyr Glu Ala Ala Gly Thr His Val Val Tyr Thr Arg Asp Thr305 310 315 320Gly Pro Gln Glu Thr Leu Gln Ala Ala Gly Pro Thr Ser His Asp Leu325 330 335Leu Leu Gln Val Leu Leu Gln Glu Pro Asn Pro Gly Ile Glu Phe Glu340 345 350Phe Trp Leu Pro Arg Glu Arg Tyr Ser Pro Phe Gln Ala Arg Val Gln355 360 365Ala Leu Gly Trp Pro Leu Arg Gln Pro Gln Pro Arg Gly Val Glu Pro370 375 380Gln Pro Pro Ala Ala Pro Ala Val Thr Pro Ala Gln Thr Pro Thr Leu385 390 395 400Ala Pro Val Phe Gln Ala Arg Val Leu Gly His His His Gln Ala Gln405 410 415Glu Thr Arg Tyr Glu Val Arg Ile Gln Leu Val Tyr Lys Asn Arg Ser420 425 430Pro Leu Arg Ala Arg Glu Tyr Val Trp Ala Pro Gly His Cys Pro Cys435 440 445Pro Met Leu Ala Pro His Arg Asp Tyr Leu Met Ala Val Gln Arg Leu450 455 460Val Ser Pro Asp Gly Thr Gln Asp Gln Leu Leu Leu Pro His Ala Gly465 470 475 480Tyr Ala Arg Pro Trp Ser Pro Ala Glu Asp Ser Arg Ile Arg Leu Thr485 490 495Ala Arg Arg Cys Pro Gly500<210>50<211>451<212>PRT<213>人(Homo sapiens)<400>50Met Asp Ser Ala Pro Leu Phe Pro Arg Pro Hi s Leu Phe Gln Asn Leu1 5 10 15Leu Leu Phe Leu Trp Ala Leu Leu Asn Cys Gly Leu Gly Val Ser Ala20 25 30Gln Gly Pro Gly Glu Trp Thr Pro Trp Val Ser Trp Thr Arg Cys Ser35 40 45Ser Ser Cys Gly Arg Gly Val Ser Val Arg Ser Arg Arg Cys Leu Arg50 55 60Leu Pro Gly Glu Glu Pro Cys Trp Gly Asp Ser His Glu Tyr Arg Leu65 70 75 80Cys Gln Leu Pro Asp Cys Pro Pro Gly Ala Val Pro Phe Arg Asp Leu85 90 95Gln Cys Ala Leu Tyr Asn Gly Arg Pro Val Leu Gly Thr Gln Lys Thr100 105 110Tyr Gln Trp Val Pro Phe His Gly Ala Pro Asn Gln Cys Asp Leu Asn115 120 125Cys Leu Ala Glu Gly His Ala Phe Tyr His Ser Phe Gly Arg Val Leu130 135 140Asp Gly Thr Ala Cys Ser Pro Gly Ala Gln Gly Val Cys Val Ala Gly145 150 155 160Arg Cys Leu Ser Ala Gly Cys Asp Gly Leu Leu Gly Ser Gly Ala Leu165 170 175Glu Asp Arg Cys Gly Arg Cys Gly Gly Ala Asn Asp Ser Cys Leu Phe180 185 190Val Gln Arg Val Phe Arg Asp Ala Gly Ala Phe Ala Gly Tyr Trp Asn195 200 205Val Thr Leu Ile Pro Glu Gly Ala Arg His Ile Arg Val Glu His Arg210 215 220Ser Arg Asn His Leu Gly Ile Leu Gly Ser Leu Met Gly Gly Asp Gly225 230 235 240Arg Tyr Val Leu Asn Gly His Trp Val Val Ser Pro Pro Gly Thr Tyr245 250 255Glu Ala Ala Gly Thr His Val Val Tyr Thr Arg Asp Thr Gly Pro Gln260 265 270Glu Thr Leu Gln Ala Ala Gly Pro Thr Ser His Asp Leu Leu Leu Gln275 280 285Val Leu Leu Gln Glu Pro Asn Pro Gly Ile Glu Phe Glu Phe Trp Leu290 295 300Pro Arg Glu Arg Tyr Ser Pro Phe Gln Ala Arg Val Gln Ala Leu Gly305 310 315 320Trp Pro Leu Arg Gln Pro Gln Pro Arg Gly Val Glu Pro Gln Pro Pro325 330 335Ala Ala Pro Ala Val Thr Pro Ala Gln Thr Pro Thr Leu Ala Pro Val340 345 350Phe Gln Ala Arg Val Leu Gly His His His Gln Ala Gln Glu Thr Arg355 360 365Tyr Glu Val Arg Ile Gln Leu Val Tyr Lys Asn Arg Ser Pro Leu Arg370 375 380Ala Arg Glu Tyr Val Trp Ala Pro Gly His Cys Pro Cys Pro Met Leu385 390 395 400Ala Pro His Arg Asp Tyr Leu Met Ala Val Gln Arg Leu Val Ser Pro405 410 415Asp Gly Thr Gln Asp Gln Leu Leu Leu Pro His Ala Gly Tyr Ala Arg420 425 430Pro Trp Ser Pro Ala Glu Asp Ser Arg Ile Arg Leu Thr Ala Arg Arg435 440 445Cys Pro Gly450<210>51<211>431<212>PRT<213>人(Homo sapiens)<400>51Met Ile Arg Thr Pro Leu Ser Ala Ser Ala Hi s Arg Leu Leu Leu Pro1 5 10 15Gly Ser Arg Gly Arg Pro Pro Arg Asn Met Gln Pro Thr Gly Arg Glu20 25 30Gly Ser Arg Ala Leu Ser Arg Arg Tyr Leu Arg Arg Leu Leu Leu Leu35 40 45Leu Leu Leu Leu Leu Leu Arg Gln Pro Val Thr Arg Ala Glu Thr Thr50 55 60Pro Gly Ala Pro Arg Ala Leu Ser Thr Leu Gly Ser Pro Ser Leu Phe65 70 75 80Thr Thr Pro Gly Val Pro Ser Ala Leu Thr Thr Pro Gly Leu Thr Thr85 90 95Pro Gly Thr Pro Lys Thr Leu Asp Leu Arg Gly Arg Ala Gln Ala Leu100 105 110Met Arg Ser Phe Pro Leu Val Asp Gly Tyr Val Gly Leu Asn Ser Ser115 120 125Gln Lys Leu Ala Cys Leu Ile Gly Val Glu Gly Gly His Ser Leu Asp130 135 140Ser Ser Leu Ser Val Leu Arg Ser Phe Tyr Val Leu Gly Val Arg Tyr145 150 155 160Leu Thr Leu Thr Phe Thr Cys Ser Thr Pro Trp Ala Glu Ser Ser Thr165 170 175Lys Phe Arg His His Met Tyr Thr Asn Val Ser Gly Leu Thr Ser Phe180 185 190Gly Glu Lys Val Val Glu Glu Leu Asn Arg Leu Gly Met Met Ile Asp195 200 205Leu Ser Tyr Ala Ser Asp Thr Leu Ile Arg Arg Val Leu Glu Val Ser210 215 220Gln Ala Pro Val Ile Phe Ser His Ser Ala Ala Arg Ala Val Cys Asp225 230 235 240Asn Leu Leu Asn Val Pro Asp Asp Ile Leu Gln Leu Leu Lys Lys Asn245 250 255Gly Gly Ile Val Met Val Thr Leu Ser Met Gly Val Leu Gln Cys Asn260 265 270Leu Leu Ala Asn Val Ser Thr Val Ala Asp Asp Ser Asn Arg Cys Ser275 280 285Val Pro Val Ile Gly Ser Glu Phe Ile Gly Ile Gly Gly Asn Tyr Asp290 295 300Gly Thr Gly Arg Phe Pro Gln Gly Leu Glu Asp Val Ser Thr Tyr Pro305 310 315 320Val Leu Ile Glu Glu Leu Leu Ser Arg Ser Trp Ser Glu Glu Glu Leu325 330 335Gln Gly Val Leu Arg Gly Asn Leu Leu Arg Val Phe Arg Gln Val Glu340 345 350Lys Val Arg Glu Glu Ser Arg Ala Gln Ser Pro Val Glu Ala Glu Phe355 360 365Pro Tyr Gly Gln Leu Ser Thr Ser Cys His Ser His Leu Val Pro Gln370 375 380Asn Gly His Gln Ala Thr His Leu Glu Val Thr Lys Gln Pro Thr Asn385 390 395 400Arg Val Pro Trp Arg Ser Ser Asn Ala Ser Pro Tyr Leu Val Pro Gly405 410 415Leu Val Ala Ala Ala Thr Ile Pro Thr Phe Thr Gln Trp Leu Cys420 425 430<210>52<211>480<212>PRT<213>人(Homo sapiens)<400>52Met Gln Pro Ser Gly Leu Glu Gly Pro Gly Thr Phe Gly Arg Trp Pro1 5 10 15Leu Leu Ser Leu Leu Leu Leu Leu Leu Leu Leu Gln Pro Val Thr Cys20 25 30Ala Tyr Thr Thr Pro Gly Pro Pro Arg Ala Leu Thr Thr Leu Gly Ala35 40 45Pro Arg Ala His Thr Met Pro Gly Thr Tyr Ala Pro Ser Thr Thr Leu50 55 60Ser Ser Pro Ser Thr Gln Gly Leu Gln Glu Gln Ala Arg Ala Leu Met65 70 75 80Arg Asp Phe Pro Leu Val Asp Gly His Asn Asp Leu Pro Leu Val Leu85 90 95Arg Gln Val Tyr Gln Lys Gly Leu Gln Asp Val Asn Leu Arg Asn Phe100 105 110Ser Tyr Gly Gln Thr Ser Leu Asp Arg Leu Arg Asp Gly Leu Val Gly115 120 125Ala Gln Phe Trp Ser Ala Tyr Val Pro Cys Gln Thr Gln Asp Arg Asp130 135 140Ala Leu Arg Leu Thr Leu Glu Gln Ile Asp Leu Ile Arg Arg Met Cys145 150 155 160Ala Ser Tyr Ser Glu Leu Glu Leu Val Thr Ser Ala Lys Gly Leu Asn165 170 175Ser Ser Gln Lys Leu Ala Cys Leu Ile Gly Val Glu Gly Gly His Ser180 185 190Leu Asp Ser Ser Leu Ser Val Leu Arg Ser Phe Tyr Val Leu Gly Val195 200 205Arg Tyr Leu Thr Leu Thr Phe Thr Cys Ser Thr Pro Trp Ala Glu Ser210 215 220Ser Thr Lys Phe Arg His His Met Tyr Thr Asn Val Ser Gly Leu Thr225 230 235 240Ser Phe Gly Glu Lys Val Val Glu Glu Leu Asn Arg Leu Gly Met Met245 250 255Ile Asp Leu Ser Tyr Ala Ser Asp Thr Leu Ile Arg Arg Val Leu Glu260 265 270Val Ser Gln Ala Pro Val Ile Phe Ser His Ser Ala Ala Arg Ala Val275 280 285Cys Asp Asn Leu Leu Asn Val Pro Asp Asp Ile Leu Gln Leu Leu Lys290 295 300Lys Asn Gly Gly Ile Val Met Val Thr Leu Ser Met Gly Val Leu Gln305 310 315 320Cys Asn Leu Leu Ala Asn Val Ser Thr Val Ala Asp His Phe Asp His325 330 335Ile Arg Ala Val Ile Gly Ser Glu Phe Ile Gly Ile Gly Gly Asn Tyr340 345 350Asp Gly Thr Gly Arg Phe Pro Gln Gly Leu Glu Asp Val Ser Thr Tyr355 360 365Pro Val Leu Ile Glu Glu Leu Leu Ser Arg Ser Trp Ser Glu Glu Glu370 375 380Leu Gln Gly Val Leu Arg Gly Asn Leu Leu Arg Val Phe Arg Gln Val385 390 395 400Glu Lys Val Arg Glu Glu Ser Arg Ala Gln Ser Pro Val Glu Ala Glu405 410 415Phe Pro Tyr Gly Gln Leu Ser Thr Ser Cys His Ser His Leu Val Pro420 425 430Gln Asn Gly His Gln Ala Thr His Leu Glu Val Thr Lys Gln Pro Thr435 440 445Asn Arg Val Pro Trp Arg Ser Ser Asn Ala Ser Pro Tyr Leu Val Pro450 455 460Gly Leu Val Ala Ala Ala Thr Ile Pro Thr Phe Thr Gln Trp Leu Cys465 470 475 480<210>53<211>371<212>PRT<213>人(Homo sapiens)<400>53Met Asp Ala Ala Thr Ala Pro Lys Gln Ala Trp Pro Pro Trp Pro Pro1 5 10 15Leu Leu Phe Leu Leu Leu Leu Pro Gly Gly Ser Gly Gly Ser Cys Pro20 25 30Ala Val Cys Asp Cys Thr Ser Gln Pro Gln Ala Val Leu Cys Gly His35 40 45Arg Gln Leu Glu Ala Val Pro Gly Gly Leu Pro Leu Asp Thr Glu Leu50 55 60Leu Asp Leu Ser Gly Asn Arg Leu Pro Lys Ala Gln Pro Leu Val Arg65 70 75 80Leu Gln Glu Leu Arg Leu Ser Gly Ala Cys Leu Thr Ser Ile Ala Ala85 90 95His Ala Phe His Gly Leu Thr Ala Phe His Leu Leu Asp Val Ala Asp100 105 110Asn Ala Leu Gln Thr Leu Glu Glu Thr Ala Phe Pro Ser Pro Asp Lys115 120 125Leu Val Thr Leu Arg Leu Ser Gly Asn Pro Leu Thr Cys Asp Cys Arg130 135 140Leu Leu Trp Leu Leu Arg Leu Arg His Leu Asp Phe Gly Met Ser Pro145 150 155 160Pro Ala Cys Ala Gly Pro His His Val Gln Gly Lys Ser Leu Lys Glu165 170 175Phe Ser Asp Ile Leu Pro Pro Gly His Phe Thr Cys Lys Pro Ala Leu180 185 190Ile Arg Lys Ser Gly Pro Arg Trp Val Ile Ala Glu Glu Gly Gly His195 200 205Ala Val Phe Ser Cys Ser Gly Asp Gly Asp Pro Ala Pro Thr Val Ser210 215 220Trp Met Arg Pro His Gly Ala Trp Leu Gly Arg Ala Gly Arg Val Arg225 230 235 240Val Leu Glu Asp Gly Thr Leu Glu Ile Arg Ser Val Gln Leu Arg Asp245 250 255Arg Gly Ala Tyr Val Cys Val Val Ser Asn Val Ala Gly Asn Asp Ser260 265 270Leu Arg Thr Trp Leu Glu Val Ile Gln Val Glu Pro Pro Asn Gly Thr275 280 285Leu Ser Asp Pro Asn Ile Thr Val Pro Gly Ile Pro Gly Pro Phe Phe290 295 300Leu Asp Ser Arg Gly Val Ala Met Val Leu Ala Val Gly Phe Leu Pro305 310 315 320Phe Leu Thr Ser Val Thr Leu Cys Phe Gly Leu Ile Ala Leu Trp Ser325 330 335Lys Gly Lys Gly Arg Val Lys His His Met Thr Phe Asp Phe Val Ala340 345 350Pro Arg Pro Ser Gly Asp Lys Asn Ser Gly Gly Asn Arg Val Thr Ala355 360 365Lys Leu Phe370<210>54<211>592<212>PRT<213>人(Homo sapiens)<400>54Met Asp Ala Ala Thr Ala Pro Lys Gln Ala Trp Pro Pro Trp Pro Pro1 5 10 15Leu Leu Phe Leu Leu Leu Leu Pro Gly Gly Ser Gly Gly Ser Cys Pro20 25 30Ala Val Cys Asp Cys Thr Ser Gln Pro Gln Ala Val Leu Cys Gly His35 40 45Arg Gln Leu Glu Ala Val Pro Gly Gly Leu Pro Leu Asp Thr Glu Leu50 55 60Leu Asp Leu Ser Gly Asn Arg Leu Trp Gly Leu Gln Gln Gly Met Leu65 70 75 80Ser Arg Leu Ser Leu Leu Gln Glu Leu Asp Leu Ser Tyr Asn Gln Leu85 90 95Ser Thr Leu Glu Pro Gly Ala Phe His Gly Leu Gln Ser Leu Leu Thr100 105 110Leu Arg Leu Gln Gly Asn Arg Leu Arg Ile Met Gly Pro Gly Val Phe115 120 125Ser Gly Leu Ser Ala Leu Thr Leu Leu Asp Leu Arg Leu Asn Gln Ile130 135 140Val Leu Phe Leu Asp Gly Ala Phe Gly Glu Leu Gly Ser Leu Gln Lys145 150 155 160Leu Glu Val Gly Asp Asn His Leu Val Phe Val Ala Pro Gly Ala Phe165 170 175Ala Gly Leu Ala Lys Leu Ser Thr Leu Thr Leu Glu Arg Cys Asn Leu180 185 190Ser Thr Val Pro Gly Leu Ala Leu Ala Arg Leu Pro Ala Leu Val Ala195 200 205Leu Arg Leu Arg Glu Leu Asp Ile Gly Arg Leu Pro Ala Gly Ala Leu210 215 220Arg Gly Leu Gly Gln Leu Lys Glu Leu Glu Ile Hi s Leu Trp Pro Ser225 230 235 240Leu Glu Ala Leu Asp Pro Gly Ser Leu Val Gly Leu Asn Leu Ser Ser245 250 255Leu Ala Ile Thr Arg Cys Asn Leu Ser Ser Val Pro Phe Gln Ala Leu260 265 270Tyr His Leu Ser Phe Leu Arg Val Leu Asp Leu Ser Gln Asn Pro Ile275 280 285Ser Ala Ile Pro Ala Arg Arg Leu Ser Pro Leu Val Arg Leu Gln Glu290 295 300Leu Arg Leu Ser Gly Ala Cys Leu Thr Ser Ile Ala Ala His Ala Phe305 310 315 320His Gly Leu Thr Ala Phe His Leu Leu Asp Val Ala Asp Asn Ala Leu325 330 335Gln Thr Leu Glu Glu Thr Ala Phe Pro Ser Pro Asp Lys Leu Val Thr340 345 350Leu Arg Leu Ser Gly Asn Pro Leu Thr Cys Asp Cys Arg Leu Leu Trp355 360 365Leu Leu Arg Leu Arg His Leu Asp Phe Gly Met Ser Pro Pro Ala Cys370 375 380Ala Gly Pro His His Val Gln Gly Lys Ser Leu Lys Glu Phe Ser Asp385 390 395 400Ile Leu Pro Pro Gly His Phe Thr Cys Lys Pro Ala Leu Ile Arg Lys405 410 415Ser Gly Pro Arg Trp Val Ile Ala Glu Glu Gly Gly His Ala Val Phe420 425 430Ser Cys Ser Gly Asp Gly Asp Pro Ala Pro Thr Val Ser Trp Met Arg435 440 445Pro His Gly Ala Trp Leu Gly Arg Ala Gly Arg Val Arg Val Leu Glu450 455 460Asp Gly Thr Leu Glu Ile Arg Ser Val Gln Leu Arg Asp Arg Gly Ala465 470 475 480Tyr Val Cys Val Val Ser Asn Val Ala Gly Asn Asp Ser Leu Arg Thr485 490 495Trp Leu Glu Val Ile Gln Val Glu Pro Pro Asn Gly Thr Leu Ser Asp500 505 510Pro Asn Ile Thr Val Pro Gly Ile Pro Gly Pro Phe Phe Leu Asp Ser5l5 520 525Arg Gly Val Ala Met Val Leu Ala Val Gly Phe Leu Pro Phe Leu Thr530 535 540Ser Val Thr Leu Cys Phe Gly Leu Ile Ala Leu Trp Ser Lys Gly Lys545 550 555 560Gly Arg Val Lys His His Met Thr Phe Asp Phe Val Ala Pro Arg Pro565 570 575Ser Gly Asp Lys Asn Ser Gly Gly Asn Arg Val Thr Ala Lys Leu Phe580 585 590<210>55<211>142<212>PRT<213>人(Homo sapiens)<400>55Met Ala Arg Tyr Met Leu Leu Leu Leu Leu Ala Val Trp Val Leu Thr1 5 10 15Gly Glu Leu Trp Pro Gly Ala Glu Ala Arg Ala Ala Pro Tyr Gly Val20 25 30Arg Leu Cys Gly Arg Glu Phe Ile Arg Ala Val Ile Phe Thr Cys Gly35 40 45Gly Ser Arg Trp Arg Arg Ser Asp Ile Leu Ala His Glu Ala Met Gly50 55 60Asp Thr Phe Pro Asp Ala Asp Ala Asp Glu Asp Ser Leu Ala Gly Glu65 70 75 80Leu Asp Glu Ala Met Gly Ser Ser Glu Trp Leu Ala Leu Thr Lys Ser85 90 95Pro Gln Ala Phe Tyr Arg Gly Arg Pro Ser Trp Gln Gly Thr Pro Gly100 105 110Val Leu Arg Gly Ser Arg Asp Val Leu Ala Gly Leu Ser Ser Ser Cys115 120 125Cys Lys Trp Gly Cys Ser Lys Ser Glu Ile Ser Ser Leu Cys130 135 140<210>56<211>230<212>PRT<213>人(Homo sapiens)<400>56Met Ser Glu Glu Val Thr Tyr Ala Thr Leu Thr Phe Gln Asp Ser Ala1 5 10 15Gly Ala Arg Asn Asn Arg Asp Gly Asn Asn Leu Arg Lys Arg Gly His20 25 30Pro Ala Pro Ser Pro Ile Trp Arg His Ala Ala Leu Gly Leu Val Thr35 40 45Leu Cys Leu Met Leu Leu Ile Gly Leu Val Thr Leu Gly Met Met Phe50 55 60Leu Gln Ile Ser Asn Asp Ile Asn Ser Asp Ser Glu Lys Leu Ser Gln65 70 75 80Leu Gln Lys Thr Ile Gln Gln Gln Gln Asp Asn Leu Ser Gln Gln Leu85 90 95Gly Asn Ser Asn Asn Leu Ser Met Glu Glu Glu Phe Leu Lys Ser Gln100 105 110Ile Ser Ser Leu Leu Lys Arg Gln Glu Gln Met Ala Ile Lys Leu Cys115 120 125Gln Glu Leu Ile Ile His Thr Ser Asp His Arg Cys Asn Pro Cys Pro130 135 140Lys Met Trp Gln Trp Tyr Gln Asn Ser Cys Tyr Tyr Phe Thr Thr Asn145 150 155 160Glu Glu Lys Thr Trp Ala Asn Ser Arg Lys Asp Cys Ile Asp Lys Asn165 170 175Ser Thr Leu Val Lys Ile Asp Ser Leu Glu Glu Lys Asp Phe Leu Met180 185 190Ser Gln Pro Leu Leu Met Phe Ser Phe Phe Trp Leu Gly Leu Ser Trp195 200 205Asp Ser Ser Gly Arg Ser Trp Phe Trp Glu Asp Gly Ser Val Pro Ser210 215 220Pro Ser Leu Tyr Val Ser225 230<210>57<211>194<212>PRT<213>人(Homo sapiens)<400>57Met Trp Leu Ser Pro Ala Leu Leu Leu Leu Ile Leu Pro Gly Tyr Ser1 5 10 15Ile Ala Ala Lys Ile Thr Gly Pro Thr Thr Val Asn Gly Ser Glu Gln20 25 30Gly Ser Leu Thr Val Gln Cys Ala Tyr Gly Ser Gly Trp Glu Thr Tyr35 40 45Leu Lys Trp Arg Cys Gln Gly Ala Asp Trp Asn Tyr Cys Asn Ile Leu50 55 60Val Lys Thr Asn Gly Ser Glu Gln Glu Val Lys Lys Asn Arg Val Ser65 70 75 80Ile Arg Asp Asn Gln Lys Asn His Met Phe Thr Val Thr Met Glu Asn85 90 95Leu Lys Arg Asp Asp Ala Asp Ser Tyr Trp Cys Gly Thr Glu Arg Pro100 105 110Gly Ile Asp Leu Gly Val Lys Val Gln Val Thr Ile Asn Pro Gly Thr115 120 125Gln Thr Ala Val Ser Glu Trp Thr Thr Thr Thr Ala Ser Leu Ala Phe130 135 140Thr Ala Ala Ala Thr Gln Lys Thr Ser Ser Pro Leu Thr Arg Ser Pro145 150 155 160Leu Lys Ser Thr His Phe Leu Phe Leu Phe Leu Leu Glu Leu Pro Leu165 170 175Leu Leu Ser Met Leu Gly Thr Val Leu Trp Val Asn Arg Pro Gln Arg180 185 190Arg Ser<210>58<211>333<212>PRT<213>人(Homo sapiens)<400>58Met Arg Ile Trp Trp Leu Leu Leu Ala Ile Glu Ile Cys Thr Gly Asn1 5 10 15Ile Asn Ser Gln Asp Thr Cys Arg Gln Gly His Pro Gly Ile Pro Gly20 25 30Asn Pro Gly His Asn Gly Leu Pro Gly Arg Asp Gly Arg Asp Gly Ala35 40 45Lys Gly Asp Lys Gly Asp Ala Gly Glu Pro Gly Arg Pro Gly Ser Pro50 55 60Gly Lys Asp Gly Thr Ser Gly Glu Lys Gly Glu Arg Gly Ala Asp Gly65 70 75 80Lys Val Glu Ala Lys Gly Ile Lys Gly Asp Gln Gly Ser Arg Gly Ser85 90 95Pro Gly Lys His Gly Pro Lys Gly Leu Ala Gly Pro Met Gly Glu Lys100 105 110Gly Leu Arg Gly Glu Thr Gly Pro Gln Gly Gln Lys Gly Asn Lys Gly115 120 125Asp Val Gly Pro Thr Gly Pro Glu Gly Pro Arg Gly Asn Ile Gly Pro130 135 140Leu Gly Pro Thr Gly Leu Pro Gly Pro Met Gly Pro Ile Gly Lys Pro145 150 155 160Gly Pro Lys Gly Glu Ala Gly Pro Thr Gly Pro Gln Gly Glu Pro Gly165 170 175Val Arg Gly Ile Arg Gly Trp Lys Gly Asp Arg Gly Glu Lys Gly Lys180 185 190Ile Gly Glu Thr Leu Val Leu Pro Lys Ser Ala Phe Thr Val Gly Leu195 200 205Thr Val Leu Ser Lys Phe Pro Ser Ser Asp Met Pro Ile Lys Phe Asp210 215 220Lys Ile Leu Tyr Asn Glu Phe Asn His Tyr Asp Thr Ala Ala Gly Lys225 230 235 240Phe Thr Cys His Ile Ala Gly Val Tyr Tyr Phe Thr Tyr His Ile Thr245 250 255Val Phe Ser Arg Asn Val Gln Val Ser Leu Val Lys Asn Gly Val Lys260 265 270Ile Leu His Thr Lys Asp Ala Tyr Met Ser Ser Glu Asp Gln Ala Ser275 280 285Gly Gly Ile Val Leu Gln Leu Lys Leu Gly Asp Glu Val Trp Leu Gln290 295 300Val Thr Gly Gly Glu Arg Phe Asn Gly Leu Phe Ala Asp Glu Asp Asp305 310 315 320Asp Thr Thr Phe Thr Gly Phe Leu Leu Phe Ser Ser Pro325 330<210>59<211>225<212>PRT<213>人(Homo sapiens)<400>59Met Arg Ile Trp Trp Leu Leu Leu Ala Ile Glu Ile Cys Thr Gly Asn1 5 10 15Ile Asn Ser Gln Asp Thr Cys Arg Gln Gly His Pro Gly Ile Pro Gly20 25 30Asn Pro Gly His Asn Gly Leu Pro Gly Arg Asp Gly Arg Asp Gly Ala35 40 45Lys Gly Asp Lys Gly Asp Ala Gly Glu Ala Gly Pro Thr Gly Pro Gln50 55 60Gly Glu Pro Gly Val Arg Gly Ile Arg Gly Trp Lys Gly Asp Arg Gly65 70 75 80Glu Lys Gly Lys Ile Gly Glu Thr Leu Val Leu Pro Lys Ser Ala Phe85 90 95Thr Val Gly Leu Thr Val Leu Ser Lys Phe Pro Ser Ser Asp Met Pro100 105 110Ile Lys Phe Asp Lys Ile Leu Tyr Asn Glu Phe Asn His Tyr Asp Thr115 120 125Ala Ala Gly Lys Phe Thr Cys His Ile Ala Gly Val Tyr Tyr Phe Thr130 135 140Tyr His Ile Thr Val Phe Ser Arg Asn Val Gln Val Ser Leu Val Lys145 150 155 160Asn Gly Val Lys Ile Leu His Thr Lys Asp Ala Tyr Met Ser Ser Glu165 170 175Asp Gln Ala Ser Gly Gly Ile Val Leu Gln Leu Lys Leu Gly Asp Glu180 185 190Val Trp Leu Gln Val Thr Gly Gly Glu Arg Phe Asn Gly Leu Phe Ala195 200 205Asp Glu Asp Asp Asp Thr Thr Phe Thr Gly Phe Leu Leu Phe Ser Ser210 215 220Pro225<210>60<211>205<212>PRT<213>人(Homo sapiens)<400>60Met Met Arg Thr Leu Ile Thr Thr His Pro Leu Pro Leu Leu Leu Leu1 5 10 15Pro Gln Gln Leu Leu Gln Leu Val Gln Phe Gln Glu Val Asp Thr Asp20 25 30Phe Asp Phe Pro Glu Glu Asp Lys Lys Glu Glu Phe Glu Glu Cys Leu35 40 45Glu Lys Phe Phe Ser Thr Gly Pro Ala Arg Pro Pro Thr Lys Glu Lys50 55 60Val Lys Arg Arg Val Leu Ile Glu Pro Gly Met Pro Leu Asn His Ile65 70 75 80Glu Tyr Cys Asn His Glu Ile Met Gly Lys Asn Val Tyr Tyr Lys His85 90 95Arg Trp Val Ala Glu His Tyr Phe Leu Leu Met Gln Tyr Asp Glu Leu100 105 110Gln Lys Ile Cys Tyr Asn Arg Phe Val Pro Cys Lys Asn Gly Ile Arg115 120 125Lys Cys Asn Arg Ser Lys Gly Leu Val Glu Gly Val Tyr Cys Asn Leu130 135 140Thr Glu Ala Phe Glu Ile Pro Ala Cys Lys Tyr Glu Ser Leu Tyr Arg145 150 155 160Lys Gly Tyr Val Leu Ile Thr Cys Ser Trp Gln Asn Glu Met Gln Lys165 170 175Arg Ile Pro His Thr Ile Asn Asp Leu Val Glu Pro Pro Glu His Arg180 185 190Ser Phe Leu Ser Glu Asp Gly Val Phe Val Ile Ser Pro195 200 205<210>61<211>95<212>PRT<213>人(Homo sapiens)<400>61Met Glu Val Val Leu Ile Phe Leu Cys Ser Leu Leu Ala His Ile Val1 5 10 15Leu Ala Asp Ala Val Glu Arg Glu Lys Gln Ile Asp Pro Phe His Tyr20 25 30Asp Tyr Gln Thr Leu Arg Ile Arg Gly Leu Val Cys Ala Val Val Leu35 40 45Phe Ser Ile Gly Ile Leu Leu Ile Leu Gly Cys Arg Cys Lys Cys Ser50 55 60Phe Asn Gln Lys Pro Arg Thr Pro Gly Glu Glu Glu Ala Gln Val Glu65 70 75 80Asn Leu Ile Thr Ala Asn Ala Thr Lys Leu Gln Lys Ala Glu Ser85 90 95<210>62<211>595<212>PRT<213>人(Homo sapiens)<400>62Met Glu Val Gly Met Gly Cys Trp Ala Arg Glu Val Leu Val Pro Glu1 5 10 15Gly Pro Leu Tyr Arg Val Ala Gly Thr Ala Val Ser Ile Ser Cys Asn20 25 30Val Thr Gly Tyr Glu Gly Pro Ala Gln Gln Asn Phe Glu Trp Phe Leu35 40 45Tyr Arg Pro Glu Ala Pro Asp Thr Ala Leu Gly Ile Val Ser Thr Lys50 55 60Asp Thr Gln Phe Ser Tyr Ala Val Phe Lys Ser Arg Val Val Ala Gly65 70 75 80Glu Val Gln Val Gln Arg Leu Gln Gly Asp Ala Val Val Leu Lys Ile85 90 95Ala Arg Leu Gln Ala Gln Asp Ala Gly Ile Tyr Glu Cys His Thr Pro100 105 110Ser Thr Asp Thr Arg Tyr Leu Gly Ser Tyr Ser Gly Lys Val Glu Leu115 120 125Arg Val Leu Pro Asp Val Leu Gln Val Ser Ala Ala Pro Pro Gly Pro130 135 140Arg Gly Arg Gln Ala Pro Thr Ser Pro Pro Arg Met Thr Val His Glu145 150 155 160Gly Gln Glu Leu Ala Leu Gly Cys Leu Ala Arg Thr Ser Thr Gln Lys165 170 175His Thr His Leu Ala Val Ser Phe Gly Arg Ser Val Pro Glu Ala Pro180 185 190Val Gly Arg Ser Thr Leu Gln Glu Val Val Gly Ile Arg Ser Asp Leu195 200 205Ala Val Glu Ala Gly Ala Pro Tyr Ala Glu Arg Leu Ala Ala Gly Glu210 215 220Leu Arg Leu Gly Lys Glu Gly Thr Asp Arg Tyr Arg Met Val Val Gly225 230 235 240Gly Ala Gln Ala Gly Asp Ala Gly Thr Tyr His Cys Thr Ala Ala Glu245 250 255Trp Ile Gln Asp Pro Asp Gly Ser Trp Ala Gln Ile Ala Glu Lys Arg260 265 270Ala Val Leu Ala His Val Asp Val Gln Thr Leu Ser Ser Gln Leu Ala275 280 285Val Thr Val Gly Pro Gly Glu Arg Arg Ile Gly Pro Gly Glu Pro Leu290 295 300Glu Leu Leu Cys Asn Val Ser Gly Ala Leu Pro Pro Ala Gly Arg His305 310 315 320Ala Ala Tyr Ser Val Gly Trp Glu Met Ala Pro Ala Gly His Leu Gly325 330 335Pro Gly Arg Leu Val Ala Gln Leu Asp Thr Glu Gly Val Gly Ser Leu340 345 350Gly Pro Gly Tyr Glu Gly Arg His Ile Ala Met Glu Lys Val Ala Ser355 360 365Arg Thr Tyr Arg Leu Arg Leu Glu Ala Ala Arg Pro Gly Asp Ala Gly370 375 380Thr Tyr Arg Cys Leu Ala Lys Ala Tyr Val Arg Gly Ser Gly Thr Arg385 390 395 400Leu Arg Glu Ala Ala Ser Ala Arg Ser Arg Pro Leu Pro Val His Val405 410 415Arg Glu Glu Gly Val Val Leu Glu Ala Val Ala Trp Leu Ala Gly Gly420 425 430Thr Val Tyr Arg Gly Glu Thr Ala Ser Leu Leu Cys Asn Ile Ser Val435 440 445Arg Gly Gly Pro Pro Gly Leu Arg Leu Ala Ala Ser Trp Trp Val Glu450 455 460Arg Pro Glu Asp Gly Glu Leu Ser Ser Val Pro Ala Gln Leu Val Gly465 470 475 480Gly Val Gly Gln Asp Gly Val Ala Glu Leu Gly Val Arg Pro Gly Gly485 490 495Gly Pro Val Ser Val Glu Leu Val Gly Pro Arg Ser His Arg Leu Arg500 505 510Leu His Ser Leu Gly Pro Glu Asp Glu Gly Val Tyr His Cys Ala Pro515 520 525Ser Ala Trp Val Gln His Ala Asp Tyr Ser Trp Tyr Gln Ala Gly Ser530 535 540Ala Arg Ser Gly Pro Val Thr Val Tyr Pro Tyr Met His Ala Leu Asp545 550 555 560Thr Leu Phe Val Pro Leu Leu Val Gly Thr Gly Val Ala Leu Val Thr565 570 575Gly Ala Thr Val Leu Gly Thr Ile Thr Cys Cys Phe Met Lys Arg Leu580 585 590Arg Lys Arg595<210>63<211>613<212>PRT<213>人(Homo sapiens)<400>63Met Gly Ala Leu Arg Pro Thr Leu Leu Pro Pro Ser Leu Pro Leu Leu1 5 10 15Leu Leu Leu Met Leu Gly Met Gly Cys Trp Ala Arg Glu Val Leu Val20 25 30Pro Glu Gly Pro Leu Tyr Arg Val Ala Gly Thr Ala Val Ser Ile Ser35 40 45Cys Asn Val Thr Gly Tyr Glu Gly Pro Ala Gln Gln Asn Phe Glu Trp50 55 60Phe Leu Tyr Arg Pro Glu Ala Pro Asp Thr Ala Leu Gly Ile Val Ser65 70 75 80Thr Lys Asp Thr Gln Phe Ser Tyr Ala Val Phe Lys Ser Arg Val Val85 90 95Ala Gly Glu Val Gln Val Gln Arg Leu Gln Gly Asp Ala Val Val Leu100 105 110Lys Ile Ala Arg Leu Gln Ala Gln Asp Ala Gly Ile Tyr Glu Cys His115 120 125Thr Pro Ser Thr Asp Thr Arg Tyr Leu Gly Ser Tyr Ser Gly Lys Val130 135 140Glu Leu Arg Val Leu Pro Asp Val Leu Gln Val Ser Ala Ala Pro Pro145 150 155 160Gly Pro Arg Gly Arg Gln Ala Pro Thr Ser Pro Pro Arg Met Thr Val165 170 175His Glu Gly Gln Glu Leu Ala Leu Gly Cys Leu Ala Arg Thr Ser Thr180 185 190Gln Lys His Thr His Leu Ala Val Ser Phe Gly Arg Ser Val Pro Glu195 200 205Ala Pro Val Gly Arg Ser Thr Leu Gln Glu Val Val Gly Ile Arg Ser210 215 220Asp Leu Ala Val Glu Ala Gly Ala Pro Tyr Ala Glu Arg Leu Ala Ala225 230 235 240Gly Glu Leu Arg Leu Gly Lys Glu Gly Thr Asp Arg Tyr Arg Met Val245 250 255Val Gly Gly Ala Gln Ala Gly Asp Ala Gly Thr Tyr His Cys Thr Ala260 265 270Ala Glu Trp Ile Gln Asp Pro Asp Gly Ser Trp Ala Gln Ile Ala Glu275 280 285Lys Arg Ala Val Leu Ala His Val Asp Val Gln Thr Leu Ser Ser Gln290 295 300Leu Ala Val Thr Val Gly Pro Gly Glu Arg Arg Ile Gly Pro Gly Glu305 310 315 320Pro Leu Glu Leu Leu Cys Asn Val Ser Gly Ala Leu Pro Pro Ala Gly325 330 335Arg His Ala Ala Tyr Ser Val Gly Trp Glu Met Ala Pro Ala Gly Ala340 345 350Pro Gly Pro Gly Arg Leu Val Ala Gln Leu Asp Thr Glu Gly Val Gly355 360 365Ser Leu Gly Pro Gly Tyr Glu Gly Arg His Ile Ala Met Glu Lys Val370 375 380Ala Ser Arg Thr Tyr Arg Leu Arg Leu Glu Ala Ala Arg Pro Gly Asp385 390 395 400Ala Gly Thr Tyr Arg Cys Leu Ala Lys Ala Tyr Val Arg Gly Ser Gly405 410 415Thr Arg Leu Arg Glu Ala Ala Ser Ala Arg Ser Arg Pro Leu Pro Val420 425 430His Val Arg Glu Glu Gly Val Val Leu Glu Ala Val Ala Trp Leu Ala435 440 445Gly Gly Thr Val Tyr Arg Gly Glu Thr Ala Ser Leu Leu Cys Asn Ile450 455 460Ser Val Arg Gly Gly Pro Pro Gly Leu Arg Leu Ala Ala Ser Trp Trp465 470 475 480Val Glu Arg Pro Glu Asp Gly Glu Leu Ser Ser Val Pro Ala Gln Leu485 490 495Val Gly Gly Val Gly Gln Asp Gly Val Ala Glu Leu Gly Val Arg Pro500 505 510Gly Gly Gly Pro Val Ser Val Glu Leu Val Gly Pro Arg Ser His Arg515 520 525Leu Arg Leu His Ser Leu Gly Pro Glu Asp Glu Gly Val Tyr His Cys530 535 540Ala Pro Ser Ala Trp Val Gln His Ala Asp Tyr Ser Trp Tyr Gln Ala545 550 555 560Gly Ser Ala Arg Ser Gly Pro Val Thr Val Tyr Pro Tyr Met His Ala565 570 575Leu Asp Thr Leu Phe Val Pro Leu Leu Val Gly Thr Gly Val Ala Leu580 585 590Val Thr Gly Ala Thr Val Leu Gly Thr Ile Thr Cys Cys Phe Met Lys595 600 605Arg Leu Arg Lys Arg610<210>64<211>596<212>PRT<213>人(Homo sapiens)<400>64Met Ala Ala Asn Ser Thr Ser Asp Leu His Thr Pro Gly Thr Gln Leu1 5 10 15Ser Val Ala Asp Ile Ile Val Ile Thr Val Tyr Phe Ala Leu Asn Val20 25 30Ala Val Gly Ile Trp Ser Ser Cys Arg Ala Ser Arg Asn Thr Val Asn35 40 45Gly Tyr Phe Leu Ala Gly Arg Asp Met Thr Trp Trp Pro Ile Gly Ala50 55 60Ser Leu Phe Ala Ser Ser Glu Gly Ser Gly Leu Phe Ile Gly Leu Ala65 70 75 80Gly Ser Gly Ala Ala Gly Gly Leu Ala Val Ala Gly Phe Glu Trp Asn85 90 95Ala Thr Tyr Val Leu Leu Ala Leu Ala Trp Val Phe Val Pro Ile Tyr100 105 110Ile Ser Ser Glu Ile Val Thr Leu Pro Glu Tyr Ile Gln Lys Arg Tyr115 120 125Gly Gly Gln Arg Ile Arg Met Tyr Leu Ser Val Leu Ser Leu Leu Leu130 135 140Ser Val Phe Thr Lys Ile Ser Leu Asp Leu Tyr Ala Gly Ala Leu Phe145 150 155 160Val His Ile Cys Leu Gly Trp Asn Phe Tyr Leu Ser Thr Ile Leu Thr165 170 175Leu Gly Ile Thr Ala Leu Tyr Thr Ile Ala Gly Gly Leu Ala Ala Val180 185 190Ile Tyr Thr Asp Ala Leu Gln Thr Leu Ile Met Val Val Gly Ala Val195 200 205Ile Leu Thr Ile Lys Ala Phe Asp Gln Ile Gly Gly Tyr Gly Gln Leu210 215 220Glu Ala Ala Tyr Ala Gln Ala Ile Pro Ser Arg Thr Ile Ala Asn Thr225 230 235 240Thr Cys His Leu Pro Arg Thr Asp Ala Met His Met Phe Arg Asp Pro245 250 255His Thr Gly Asp Leu Pro Trp Thr Gly Met Thr Phe Gly Leu Thr Ile260 265 270Met Ala Thr Trp Tyr Trp Cys Thr Asp Gln Val Ile Val Gln Arg Ser275 280 285Leu Ser Ala Arg Asp Leu Asn His Ala Lys Ala Gly Ser Ile Leu Ala290 295 300Ser Tyr Leu Lys Met Leu Pro Met Gly Leu Ile Ile Met Pro Gly Met305 310 315 320Ile Ser Arg Ala Leu Phe Pro Asp Asp Val Gly Cys Val Val Pro Ser325 330 335Glu Cys Leu Arg Ala Cys Gly Ala Glu Val Gly Cys Ser Asn Ile Ala340 345 350Tyr Pro Lys Leu Val Met Glu Leu Met Pro Ile Gly Leu Arg Gly Leu355 360 365Met Ile Ala Val Met Leu Ala Ala Leu Met Ser Ser Leu Thr Ser Ile370 375 380Phe Asn Ser Ser Ser Thr Leu Phe Thr Met Asp Ile Trp Arg Arg Leu385 390 395 400Arg Pro Arg Ser Gly Glu Arg Glu Leu Leu Leu Val Gly Arg Leu Val405 410 415Ile Val Ala Leu Ile Gly Val Ser Val Ala Trp Ile Pro Val Leu Gln420 425 430Asp Ser Asn Ser Gly Gln Leu Phe Ile Tyr Met Gln Ser Val Thr Ser435 440 445Ser Leu Ala Pro Pro Val Thr Ala Val Phe Val Leu Gly Val Phe Trp450 455 460Arg Arg Ala Asn Glu Gln Gly Ala Phe Trp Gly Leu Ile Ala Gly Leu465 470 475 480Val Val Gly Ala Thr Arg Leu Val Leu Glu Phe Leu Asn Pro Ala Pro485 490 495Pro Cys Gly Glu Pro Asp Thr Arg Pro Ala Val Leu Gly Ser Ile His500 505 510Tyr Leu His Phe Ala Val Ala Leu Phe Ala Leu Ser Gly Ala Val Val515 520 525Val Ala Gly Ser Leu Leu Thr Pro Pro Pro Gln Ser Val Gln Ile Glu530 535 540Asn Leu Thr Trp Trp Thr Leu Ala Gln Asp Val Pro Leu Gly Thr Lys545 550 555 560Ala Gly Asp Gly Gln Thr Pro Gln Lys His Ala Phe Trp Ala Arg Val565 570 575Cys Gly Phe Asn Ala Ile Leu Leu Met Cys Val Asn Ile Phe Phe Tyr580 585 590Ala Tyr Phe Ala595<210>65<211>393<212>PRT<213>人(Homo sapiens)<400>65Met Asp Ser Leu Lys Asn Glu Asn Tyr Asp Leu Val Phe Val Glu Ala1 5 10 15Phe Asp Phe Cys Ser Phe Leu Ile Ala Glu Lys Leu Val Lys Pro Phe20 25 30Val Ala Ile Leu Pro Thr Thr Phe Gly Ser Leu Asp Phe Gly Leu Pro35 40 45Ser Pro Leu Ser Tyr Val Pro Val Phe Pro Ser Leu Leu Thr Asp His50 55 60Met Asp Phe Trp Gly Arg Val Lys Asn Phe Leu Met Phe Phe Ser Phe65 70 75 80Ser Arg Ser Gln Trp Asp Met Gln Ser Thr Phe Asp Asn Thr Ile Lys85 90 95Glu His Phe Pro Glu Gly Ser Arg Pro Val Leu Ser His Leu Leu Leu100 105 110Lys Ala Glu Leu Trp Phe Val Asn Ser Asp Phe Ala Phe Asp Phe Ala115 120 125Arg Pro Leu Leu Pro Asn Thr Val Tyr Ile Gly Gly Leu Met Glu Lys130 135 140Pro Ile Lys Pro Val Pro Gln Asp Leu Asp Asn Phe Ile Ala Asn Phe145 150 155 160Gly Asp Ala Gly Phe Val Leu Val Ala Phe Gly Ser Met Leu Asn Thr165 170 175His Gln Ser Gln Glu Val Leu Lys Lys Met His Asn Ala Phe Ala His180 185 190Leu Pro Gln Gly Val Ile Trp Thr Cys Gln Ser Ser His Trp Pro Arg195 200 205Asp Val His Leu Ala Thr Asn Val Lys Ile Val Asp Trp Leu Pro Gln210 215 220Ser Asp Leu Leu Ala His Pro Ser Ile Arg Leu Phe Val Thr His Gly225 230 235 240Gly Gln Asn Ser Val Met Glu Ala Ile Arg His Gly Val Pro Met Val245 250 255Gly Leu Pro Val Asn Gly Asp Gln His Gly Asn Met Val Arg Val Val260 265 270Ala Lys Asn Tyr Gly Val Ser Ile Arg Leu Asn Gln Val Thr Ala Asp275 280 285Thr Leu Thr Leu Thr Met Lys Gln Val Ile Glu Asp Lys Arg Tyr Lys290 295 300Ser Ala Val Val Ala Ala Ser Val Ile Leu His Ser Gln Pro Leu Ser305 310 315 320Pro Ala Gln Arg Leu Val Gly Trp Ile Asp His Ile Leu Gln Thr Gly325 330 335Gly Ala Thr His Leu Lys Pro Tyr Ala Phe Gln Gln Pro Trp His Glu340 345 350Gln Tyr Leu Ile Asp Val Phe Val Phe Leu Leu Gly Leu Thr Leu Gly355 360 365Thr Met Trp Leu Cys Gly Lys Leu Leu Gly Val Val Ala Arg Trp Leu370 375 380Arg Gly Ala Arg Lys Val Lys Lys Thr385 390<210>66<211>523<212>PRT<213>人(Homo sapiens)<400>66Met Val Gly Gln Arg Val Leu Leu Leu Val Ala Phe Leu Leu Ser Gly1 5 10 15Val Leu Leu Ser Glu Ala Ala Lys Ile Leu Thr Ile Ser Thr Leu Gly20 25 30Gly Ser His Tyr Leu Leu Leu Asp Arg Val Ser Gln Ile Leu Gln Glu35 40 45His Gly His Asn Val Thr Met Leu His Gln Ser Gly Lys Phe Leu Ile50 55 60Pro Asp Ile Lys Glu Glu Glu Lys Ser Tyr Gln Val Ile Arg Trp Phe65 70 75 80Ser Pro Glu Asp His Gln Lys Arg Ile Lys Lys His Phe Asp Ser Tyr85 90 95Ile Glu Thr Ala Leu Asp Gly Arg Lys Glu Ser Glu Ala Leu Val Lys100 105 110Leu Met Glu Ile Phe Gly Thr Gln Cys Ser Tyr Leu Leu Ser Arg Lys115 120 125Asp Ile Met Asp Ser Leu Lys Asn Glu Asn Tyr Asp Leu Val Phe Val130 135 140Glu Ala Phe Asp Phe Cys Ser Phe Leu Ile Ala Glu Lys Leu Val Lys145 150 155 160Pro Phe Val Ala Ile Leu Pro Thr Thr Phe Gly Ser Leu Asp Phe Gly165 170 175Leu Pro Ser Pro Leu Ser Tyr Val Pro Val Phe Pro Ser Leu Leu Thr180 185 190Asp His Met Asp Phe Trp Gly Arg Val Lys Asn Phe Leu Met Phe Phe195 200 205Ser Phe Ser Arg Ser Gln Trp Asp Met Gln Ser Thr Phe Asp Asn Thr210 215 220Ile Lys Glu His Phe Pro Glu Gly Ser Arg Pro Val Leu Ser His Leu225 230 235 240Leu Leu Lys Ala Glu Leu Trp Phe Val Asn Ser Asp Phe Ala Phe Asp245 250 255Phe Ala Arg Pro Leu Leu Pro Asn Thr Val Tyr Ile Gly Gly Leu Met260 265 270Glu Lys Pro Ile Lys Pro Val Pro Gln Asp Leu Asp Asn Phe Ile Ala275 280 285Asn Phe Gly Asp Ala Gly Phe Val Leu Val Ala Phe Gly Ser Met Leu290 295 300Asn Thr His Gln Ser Gln Glu Val Leu Lys Lys Met His Asn Ala Phe305 310 315 320Ala His Leu Pro Gln Gly Val Ile Trp Thr Cys Gln Ser Ser His Trp325 330 335Pro Arg Asp Val His Leu Ala Thr Asn Val Lys Ile Val Asp Trp Leu340 345 350Pro Gln Ser Asp Leu Leu Ala His Pro Ser Ile Arg Leu Phe Val Thr355 360 365His Gly Gly Gln Asn Ser Val Met Glu Ala Ile Arg His Gly Val Pro370 375 380Met Val Gly Leu Pro Val Asn Gly Asp Gln His Gly Asn Met Val Arg385 390 395 400Val Val Ala Lys Asn Tyr Gly Val Ser Ile Arg Leu Asn Gln Val Thr405 410 415Ala Asp Thr Leu Thr Leu Thr Met Lys Gln Val Ile Glu Asp Lys Arg420 425 430Tyr Lys Ser Ala Val Val Ala Ala Ser Val Ile Leu His Ser Gln Pro435 440 445Leu Ser Pro Ala Gln Arg Leu Val Gly Trp Ile Asp His Ile Leu Gln450 455 460Thr Gly Gly Ala Thr His Leu Lys Pro Tyr Ala Phe Gln Gln Pro Trp465 470 475 480His Glu Gln Tyr Leu Ile Asp Val Phe Val Phe Leu Leu Gly Leu Thr485 490 495Leu Gly Thr Met Trp Leu Cys Gly Lys Leu Leu Gly Val Val Ala Arg500 505 510Trp Leu Arg Gly Ala Arg Lys Val Lys Lys Thr515 520<210>67<211>252<212>PRT<213>人(Homo sapiens)<400>67Met Ser Cys Val Leu Gly Gly Val Ile Pro Leu Gly Leu Leu Phe Leul 5 10 15Val Cys Gly Ser Gln Gly Tyr Leu Leu Pro Asn Val Thr Leu Leu Glu20 25 30Glu Leu Leu Ser Lys Tyr Gln His Asn Glu Ser His Ser Arg Val Arg35 40 45Arg Ala Ile Pro Arg Glu Asp Lys Glu Glu Ile Leu Met Leu His Asn50 55 60Lys Leu Arg Gly Gln Val Gln Pro Gln Ala Ser Asn Met Glu Tyr Met65 70 75 80Thr Trp Asp Asp Glu Leu Glu Lys Ser Ala Ala Ala Trp Ala Ser Gln85 90 95Cys Ile Trp Glu His Gly Pro Thr Ser Leu Leu Val Ser Ile Gly Gln100 105 110Asn Leu Gly Ala His Trp Gly Arg Tyr Arg Ser Pro Gly Phe His Val115 120 125Gln Ser Trp Tyr Asp Glu Val Lys Asp Tyr Thr Tyr Pro Tyr Pro Ser130 135 140Glu Cys Asn Pro Trp Cys Pro Glu Arg Cys Ser Gly Pro Met Cys Thr145 150 155 160His Tyr Thr Gln Ile Val Trp Ala Thr Thr Asn Lys Ile Gly Cys Ala165 170 175Val Asn Thr Cys Arg Lys Met Thr Val Trp Gly Glu Val Trp Glu Asn180 185 190Ala Val Tyr Phe Val Cys Asn Tyr Ser Pro Lys Gly Asn Trp Ile Gly195 200 205Glu Ala Pro Tyr Lys Asn Gly Arg Pro Cys Ser Glu Cys Pro Pro Ser210 215 220Tyr Gly Gly Ser Cys Arg Asn Asn Leu Cys Tyr Arg Gly Arg Lys Phe225 230 235 240Thr Pro Asn Thr Phe Ala Met Asn Leu Pro Ser Val245 250<210>68<211>497<212>PRT<213>人(Homo sapiens)<400>68Met Ser Cys Val Leu Gly Gly Val Ile Pro Leu Gly Leu Leu Phe Leu1 5 10 15Val Cys Gly Ser Gln Gly Tyr Leu Leu Pro Asn Val Thr Leu Leu Glu20 25 30Glu Leu Leu Ser Lys Tyr Gln His Asn Glu Ser His Ser Arg Val Arg35 40 45Arg Ala Ile Pro Arg Glu Asp Lys Glu Glu Ile Leu Met Leu His Asn50 55 60Lys Leu Arg Gly Gln Val Gln Pro Gln Ala Ser Asn Met Glu Tyr Met65 70 75 80Thr Trp Asp Asp Glu Leu Glu Lys Ser Ala Ala Ala Trp Ala Ser Gln85 90 95Cys Ile Trp Glu His Gly Pro Thr Ser Leu Leu Val Ser Ile Gly Gln100 105 110Asn Leu Gly Ala His Trp Gly Arg Tyr Arg Ser Pro Gly Phe His Val115 120 125Gln Ser Trp Tyr Asp Glu Val Lys Asp Tyr Thr Tyr Pro Tyr Pro Ser130 135 140Glu Cys Asn Pro Trp Cys Pro Glu Arg Cys Ser Gly Pro Met Cys Thr145 150 155 160His Tyr Thr Gln Ile Val Trp Ala Thr Thr Asn Lys Ile Gly Cys Ala165 170 175Val Asn Thr Cys Arg Lys Met Thr Val Trp Gly Glu Val Trp Glu Asn180 185 190Ala Val Tyr Phe Val Cys Asn Tyr Ser Pro Lys Gly Asn Trp Ile Gly195 200 205Glu Ala Pro Tyr Lys Asn Gly Arg Pro Cys Ser Glu Cys Pro Pro Ser210 215 220Tyr Gly Gly Ser Cys Arg Asn Asn Leu Cys Tyr Arg Glu Glu Thr Tyr225 230 235 240Thr Pro Lys Pro Glu Thr Asp Glu Met Asn Glu Val Glu Thr Ala Pro245 250 255Ile Pro Glu Glu Asn His Val Trp Leu Gln Pro Arg Val Met Arg Pro260 265 270Thr Lys Pro Lys Lys Thr Ser Ala Val Asn Tyr Met Thr Gln Val Val275 280 285Arg Cys Asp Thr Lys Met Lys Asp Arg Cys Lys Gly Ser Thr Cys Asn290 295 300Arg Tyr Gln Cys Pro Ala Gly Cys Leu Asn His Lys Ala Lys Ile Phe305 310 315 320Gly Thr Leu Phe Tyr Glu Ser Ser Ser Ser Ile Cys Arg Ala Ala Ile325 330 335His Tyr Gly Ile Leu Asp Asp Lys Gly Gly Leu Val Asp Ile Thr Arg340 345 350Asn Gly Lys Val Pro Phe Phe Val Lys Ser Glu Arg His Gly Val Gln355 360 365Ser Leu Ser Lys Tyr Lys Pro Ser Ser Ser Phe Met Val Ser Lys Val370 375 380Lys Val Gln Asp Leu Asp Cys Tyr Thr Thr Val Ala Gln Leu Cys Pro385 390 395 400Phe Glu Lys Pro Ala Thr His Cys Pro Arg Ile His Cys Pro Ala His405 410 415Cys Lys Asp Glu Pro Ser Tyr Trp Ala Pro Val Phe Gly Thr Asn Ile420 425 430Tyr Ala Asp Thr Ser Ser Ile Cys Lys Thr Ala Val His Ala Gly Val435 440 445Ile Ser Asn Glu Ser Gly Gly Asp Val Asp Val Met Pro Val Asp Lys450 455 460Lys Lys Thr Tyr Val Gly Ser Leu Arg Asn Gly Val Gln Ser Glu Ser465 470 475 480Leu Gly Thr Pro Arg Asp Gly Lys Ala Phe Arg Ile Phe Ala Val Arg485 490 495Gln<210>69<211>438<212>PRT<213>人(Homo sapiens)<400>69Asx Met Leu His Asn Lys Leu Arg Gly Gln Val Gln Pro Gln Ala Ser1 5 10 15Asn Met Glu Tyr Met Thr Trp Asp Asp Glu Leu Glu Lys Ser Ala Ala20 25 30Ala Trp Ala Ser Gln Cys Ile Trp Glu His Gly Pro Thr Ser Leu Leu35 40 45Val Ser Ile Gly Gln Asn Leu Gly Ala His Trp Gly Arg Tyr Arg Ser50 55 60Pro Gly Phe His Val Gln Ser Trp Tyr Asp Glu Val Lys Asp Tyr Thr65 70 75 80Tyr Pro Tyr Pro Ser Glu Cys Asn Pro Trp Cys Pro Glu Arg Cys Ser85 90 95Gly Pro Met Cys Thr His Tyr Thr Gln Ile Val Trp Ala Thr Thr Asn100 105 110Lys Ile Gly Cys Ala Val Asn Thr Cys Arg Lys Met Thr Val Trp Gly115 120 125Glu Val Trp Glu Asn Ala Val Tyr Phe Val Cys Asn Tyr Ser Pro Lys130 135 140Gly Asn Trp Ile Gly Glu Ala Pro Tyr Lys Asn Gly Arg Pro Cys Ser145 150 155 160Glu Cys Pro Pro Ser Tyr Gly Gly Ser Cys Arg Asn Asn Leu Cys Tyr165 170 175Arg Glu Glu Thr Tyr Thr Pro Lys Pro Glu Thr Asp Glu Met Asn Glu180 185 190Val Glu Thr Ala Pro Ile Pro Glu Glu Asn His Val Trp Leu Gln Pro195 200 205Arg Val Met Arg Pro Thr Lys Pro Lys Lys Thr Ser Ala Val Asn Tyr210 215 220Met Thr Gln Val Val Arg Cys Asp Thr Lys Met Lys Asp Arg Cys Lys225 230 235 240Gly Ser Thr Cys Asn Arg Tyr Gln Cys Pro Ala Gly Cys Leu Asn His245 250 255Lys Ala Lys Ile Phe Gly Thr Leu Phe Tyr Glu Ser Ser Ser Ser Ile260 265 270Cys Arg Ala Ala Ile His Tyr Gly Ile Leu Asp Asp Lys Gly Gly Leu275 280 285Val Asp Ile Thr Arg Asn Gly Lys Val Pro Phe Phe Val Lys Ser Glu290 295 300Arg His Gly Val Gln Ser Leu Ser Lys Tyr Lys Pro Ser Ser Ser Phe305 310 315 320Met Val Ser Lys Val Lys Val Gln Asp Leu Asp Cys Tyr Thr Thr Val325 330 335Ala Gln Leu Cys Pro Phe Glu Lys Pro Ala Thr His Cys Pro Arg Ile340 345 350His Cys Pro Ala His Cys Lys Asp Glu Pro Ser Tyr Trp Ala Pro Val355 360 365Phe Gly Thr Asn Ile Tyr Ala Asp Thr Ser Ser Ile Cys Lys Thr Ala370 375 380Val His Ala Gly Val Ile Ser Asn Glu Ser Gly Gly Asp Val Asp Val385 390 395 400Met Pro Val Asp Lys Lys Lys Thr Tyr Val Gly Ser Leu Arg Asn Gly405 410 415Val Gln Ser Glu Ser Leu Gly Thr Pro Arg Asp Gly Lys Ala Phe Arg420 425 430Ile Phe Ala Val Arg Gln435<210>70<211>308<212>PRT<213>人(Homo sapiens)<400>70Met Val Gly Gly Val Leu Ala Ser Leu Gly Phe Val Phe Ser Ala Phe1 5 10 15Ala Ser Asp Leu Leu His Leu Tyr Leu Gly Leu Gly Leu Leu Ala Gly20 25 30Phe Gly Trp Ala Leu Val Phe Ala Pro Ala Leu Gly Thr Leu Ser Arg35 40 45Tyr Phe Ser Arg Arg Arg Val Leu Ala Val Gly Leu Ala Leu Thr Gly50 55 60Asn Gly Ala Ser Ser Leu Leu Leu Ala Pro Ala Leu Gln Leu Leu Leu65 70 75 80Asp Thr Phe Gly Trp Arg Gly Ala Leu Leu Leu Leu Gly Ala Ile Thr85 90 95Leu His Leu Thr Pro Cys Gly Ala Leu Leu Leu Pro Leu Val Leu Pro100 105 110Gly Asp Pro Pro Ala Pro Pro Arg Ser Pro Leu Ala Ala Leu Gly Leu115 120 125Ser Leu Phe Thr Arg Arg Ala Phe Ser Ile Phe Ala Leu Gly Thr Ala130 135 140Leu Val Gly Gly Gly Tyr Phe Val Pro Tyr Val His Leu Ala Pro His145 150 155 160Ala Leu Asp Arg Gly Leu Gly Gly Tyr Gly Ala Ala Leu Val Val Ala165 170 175Val Ala Ala Met Gly Asp Ala Gly Ala Arg Leu Val Cys Gly Trp Leu180 185 190Ala Asp Gln Gly Trp Val Pro Leu Pro Arg Leu Leu Ala Val Phe Gly195 200 205Ala Leu Thr Gly Leu Gly Leu Trp Val Val Gly Leu Val Pro Val Val210 215 220Gly Gly Glu Glu Ser Trp Gly Gly Pro Leu Leu Ala Ala Ala Val Ala225 230 235 240Tyr Gly Leu Ser Ala Gly Ser Tyr Ala Pro Leu Val Phe Gly Val Leu245 250 255Pro Gly Leu Val Gly Val Gly Gly Val Val Gln Ala Thr Gly Leu Val260 265 270Met Met Leu Met Ser Leu Gly Gly Leu Leu Gly Pro Pro Leu Ser Gly275 280 285Lys Asp Leu Ser Ser Gln Ile Cys Leu Gln Leu Ser Ser Ala Pro Gly290 295 300Val Arg Gly Phe305<210>71<211>447<212>PRT<213>人(Homo sapiens)<400>71Met Thr Pro Gln Pro Ala Gly Pro Pro Asp Gly Gly Trp Gly Trp Val1 5 10 15Val Ala Ala Ala Ala Phe Ala Ile Asn Gly Leu Ser Tyr Gly Leu Leu20 25 30Arg Ser Leu Gly Leu Ala Phe Pro Asp Leu Ala Glu His Phe Asp Arg35 40 45Ser Ala Gln Asp Thr Ala Trp Ile Ser Ala Leu Ala Leu Ala Val Gln50 55 60Gln Ala Ala Ser Pro Val Gly Ser Ala Leu Ser Thr Arg Trp Gly Ala65 70 75 80Arg Pro Val Val Met Val Gly Gly Val Leu Ala Ser Leu Gly Phe Val85 90 95Phe Ser Ala Phe Ala Ser Asp Leu Leu His Leu Tyr Leu Gly Leu Gly100 105 110Leu Leu Ala Gly Phe Gly Trp Ala Leu Val Phe Ala Pro Ala Leu Gly115 120 125Thr Leu Ser Arg Tyr Phe Ser Arg Arg Arg Val Leu Ala Val Gly Leu130 135 140Ala Leu Thr Gly Asn Gly Ala Ser Ser Leu Leu Leu Ala Pro Ala Leu145 150 155 160Gln Leu Leu Leu Asp Thr Phe Gly Trp Arg Gly Ala Leu Leu Leu Leu165 170 175Gly Ala Ile Thr Leu His Leu Thr Pro Cys Gly Ala Leu Leu Leu Pro180 185 190Leu Val Leu Pro Gly Asp Pro Pro Ala Pro Pro Arg Ser Pro Leu Ala195 200 205Ala Leu Gly Leu Ser Leu Phe Thr Arg Arg Ala Phe Ser Ile Phe Ala210 215 220Leu Gly Thr Ala Leu Val Gly Gly Gly Tyr Phe Val Pro Tyr Val His225 230 235 240Leu Ala Pro His Ala Leu Asp Arg Gly Leu Gly Gly Tyr Gly Ala Ala245 250 255Leu Val Val Ala Val Ala Ala Met Gly Asp Ala Gly Ala Arg Leu Val260 265 270Cys Gly Trp Leu Ala Asp Gln Gly Trp Val Pro Leu Pro Arg Leu Leu275 280 285Ala Val Phe Gly Ala Leu Thr Gly Leu Gly Leu Trp Val Val Gly Leu290 295 300Val Pro Val Val Gly Gly Glu Glu Ser Trp Gly Gly Pro Leu Leu Ala305 310 315 320Ala Ala Val Ala Tyr Gly Leu Ser Ala Gly Ser Tyr Ala Pro Leu Val325 330 335Phe Gly Val Leu Pro Gly Leu Val Gly Val Gly Gly Val Val Gln Ala340 345 350Thr Gly Leu Val Met Met Leu Met Ser Leu Gly Gly Leu Leu Gly Pro355 360 365Pro Leu Ser Gly Phe Leu Arg Asp Glu Thr Gly Asp Phe Thr Ala Ser370 375 380Phe Leu Leu Ser Gly Ser Leu Ile Leu Ser Gly Ser Phe Ile Tyr Ile385 390 395 400Gly Leu Pro Arg Ala Leu Pro Ser Cys Gly Pro Ala Ser Pro Pro Ala405 410 415Thr Pro Pro Pro Glu Thr Gly Glu Leu Leu Pro Ala Pro Gln Ala Val420 425 430Leu Leu Ser Pro Gly Gly Pro Gly Ser Thr Leu Asp Thr Thr Cys435 440 445<210>72<211>458<212>PRT<213>人(Homo sapiens)<400>72Asx Met Ala Arg Arg Thr Glu Pro Pro Asp Gly Gly Trp Gly Trp Val1 5 10 15Val Val Leu Ser Ala Phe Phe Gln Ser Ala Leu Val Phe Gly Val Leu20 25 30Arg Ser Phe Gly Val Phe Phe Val Glu Phe Val Ala Ala Phe Glu Glu35 40 45Gln Ala Ala Arg Val Ser Trp Ile Ala Ser Ile Gly Ile Ala Val Gln50 55 60Gln Phe Gly Ser Pro Val Gly Ser Ala Leu Ser Thr Lys Phe Gly Pro65 70 75 80Arg Pro Val Val Met Thr Gly Gly Ile Leu Ala Ala Leu Gly Met Leu85 90 95Leu Ala Ser Phe Ala Thr Ser Leu Thr His Leu Tyr Leu Ser Ile Gly100 105 110Leu Leu Ser Gly Ser Gly Trp Ala Leu Thr Phe Ala Pro Thr Leu Ala115 120 125Cys Leu Ser Cys Tyr Phe Ser Arg Arg Arg Ser Leu Ala Thr Gly Leu130 135 140Ala Leu Thr Gly Val Gly Leu Ser Ser Phe Thr Phe Ala Pro Phe Phe145 150 155 160Gln Trp Leu Leu Ser His Tyr Ala Trp Arg Gly Ser Leu Leu Leu Val165 170 175Ser Ala Leu Ser Leu His Leu Val Ala Cys Gly Ala Leu Leu Arg Pro180 185 190Pro Ser Leu Ala Glu Asp Pro Ala Val Gly Gly Pro Arg Ala Gln Leu195 200 205Thr Ser Leu Leu His His Gly Pro Phe Leu Arg Tyr Thr Val Ala Leu210 215 220Thr Leu Ile Asn Thr Gly Tyr Phe Ile Pro Tyr Leu His Leu Val Ala225 230 235 240His Leu Gln Asp Leu Asp Trp Asp Pro Leu Pro Ala Ala Phe Leu Leu245 250 255Ser Val Val Ala Ile Ser Asp Leu Val Gly Arg Val Val Ser Gly Trp260 265 270Leu Gly Asp Ala Val Pro Gly Pro Val Thr Arg Leu Leu Met Leu Trp275 280 285Thr Thr Leu Thr Gly Val Ser Leu Ala Leu Phe Pro Val Ala Gln Ala290 295 300Pro Thr Ala Leu Val Ala Leu Ala Val Ala Tyr Gly Phe Thr Ser Gly305 310 315 320Ala Leu Ala Pro Leu Ala Phe Ser Val Leu Pro Glu Leu Ile Gly Thr325 330 335Arg Arg Ile Tyr Cys Gly Leu Gly Leu Leu Gln Met Ile Glu Ser Ile340 345 350Gly Gly Leu Leu Gly Pro Pro Leu Ser Gly Tyr Leu Arg Asp Val Ser355 360 365Gly Asn Tyr Thr Ala Ser Phe Val Val Ala Gly Ala Phe Leu Leu Ser370 375 380Gly Ser Gly Ile Leu Leu Thr Leu Pro His Phe Phe Cys Phe Ser Thr385 390 395 400Thr Thr Ser Gly Pro Gln Asp Leu Val Thr Glu Ala Leu Asp Thr Lys405 410 415Val Pro Leu Pro Lys Glu Gly Leu Glu Gly Gly Leu Asn Ser Thr Glu420 425 430Ser Gly Pro Glu Ser Gln Ser Leu Thr Ala Pro Gly Leu Leu Leu Pro435 440 445Arg Leu Gly Leu His Arg Thr Thr Val Pro450 455<210>73<211>169<212>PRT<213>人(Homo sapiens)<400>73Met Thr Met Lys Thr Ser Gly Ala Thr Cys Asp Ala Asn Ser Val Met1 5 10 15Asn Cys Gly Ile Arg Gly Ser Glu Met Phe Ala Glu Met Asp Leu Arg20 25 30Ala Ile Lys Pro Tyr Gln Thr Leu Ile Lys Lys Val Gly Gln Arg His35 40 45Cys Val Asp Pro Ala Val Ile Ala Ala Ile Ile Ser Arg Glu Ser His50 55 60Gly Gly Ser Val Leu Gln Asp Gly Trp Asp His Arg Gly Leu Lys Phe65 70 75 80Gly Leu Met Gln Leu Asp Lys Gln Thr Tyr His Pro Val Gly Ala Trp85 90 95Asp Ser Lys Glu His Leu Ser Gln Ala Thr Gly Ile Leu Thr Glu Arg100 105 110Ile Lys Ala Ile Gln Lys Lys Phe Pro Thr Trp Ser Val Ala Gln His115 120 125Leu Lys Gly Gly Leu Ser Ala Phe Lys Ser Gly Ile Glu Ala Ile Ala130 135 140Thr Pro Ser Asp Ile Asp Asn Asp Phe Val Asn Asp Ile Ile Ala Arg145 150 155 160Ala Lys Phe Tyr Lys Arg Gln Ser Phe165<210>74<211>186<212>PRT<213>人(Homo sapiens)<400>74Met Lys Pro His Leu His Pro Arg Leu Tyr His Gly Cys Tyr Gly Asp1 5 10 15Ile Met Thr Met Lys Thr Ser Gly Ala Thr Cys Asp Ala Asn Ser Val20 25 30Met Asn Cys Gly Ile Arg Gly Ser Glu Met Phe Ala Glu Met Asp Leu35 40 45Arg Ala Ile Lys Pro Tyr Gln Thr Leu Ile Lys Lys Val Gly Gln Arg50 55 60His Cys Val Asp Pro Ala Val Ile Ala Ala Ile Ile Ser Arg Glu Ser65 70 75 80His Gly Gly Ser Val Leu Gln Asp Gly Trp Asp His Arg Gly Leu Lys85 90 95Phe Gly Leu Met Gln Leu Asp Lys Gln Thr Tyr His Pro Val Gly Ala100 105 110Trp Asp Ser Lys Glu His Leu Ser Gln Ala Thr Gly Ile Leu Thr Glu115 120 125Arg Ile Lys Ala Ile Gln Lys Lys Phe Pro Thr Trp Ser Val Ala Gln130 135 140His Leu Lys Gly Gly Leu Ser Ala Phe Lys Ser Gly Ile Glu Ala Ile145 150 155 160Ala Thr Pro Ser Asp Ile Asp Asn Asp Phe Val Asn Asp Ile Ile Ala165 170 175Arg Ala Lys Phe Tyr Lys Arg Gln Ser Phe180 185<210>75<211>675<212>PRT<213>人(Homo sapiens)<400>75Met Glu Ser Gly Thr Ser Ser Pro Gln Pro Pro Gln Leu Asp Pro Leu1 5 10 15Asp Ala Phe Pro Gln Lys Gly Leu Glu Pro Gly Asp Ile Ala Val Leu20 25 30Val Leu Tyr Phe Leu Phe Val Leu Ala Val Gly Leu Trp Ser Thr Val35 40 45Lys Thr Lys Arg Asp Thr Val Lys Gly Tyr Phe Leu Ala Gly Gly Asp50 55 60Met Val Trp Trp Pro Val Gly Ala Ser Leu Phe Ala Ser Asn Val Gly65 70 75 80Ser Gly His Phe Ile Gly Leu Ala Gly Ser Gly Ala Ala Thr Gly Ile85 90 95Ser Val Ser Ala Tyr Glu Leu Asn Gly Leu Phe Ser Val Leu Met Leu100 105 110Ala Trp Ile Phe Leu Pro Ile Tyr Ile Ala Gly Gln Val Thr Thr Met115 120 125Pro Glu Tyr Leu Arg Lys Arg Phe Gly Gly Ile Arg Ile Pro Ile Ile130 135 140Leu Ala Val Leu Tyr Leu Phe Ile Tyr Ile Phe Thr Lys Ile Ser Val145 150 155 160Asp Met Tyr Ala Gly Ala Ile Phe Ile Gln Gln Ser Leu His Leu Asp165 170 175Leu Tyr Leu Ala Ile Val Gly Leu Leu Ala Ile Thr Ala Val Tyr Thr180 185 190Val Ala Gly Gly Leu Ala Ala Val Ile Tyr Thr Asp Ala Leu Gln Thr195 200 205Leu Ile Met Leu Ile Gly Ala Leu Thr Leu Met Gly Tyr Ser Phe Ala210 215 220Ala Val Gly Gly Met Glu Gly Leu Lys Glu Lys Tyr Phe Leu Ala Leu225 230 235 240Ala Ser Asn Arg Ser Glu Asn Ser Ser Cys Gly Leu Pro Arg Glu Asp245 250 255Ala Phe His Ile Phe Arg Asp Pro Leu Thr Ser Asp Leu Pro Trp Pro260 265 270Gly Val Leu Phe Gly Met Ser Ile Pro Ser Leu Trp Tyr Trp Cys Thr275 280 285Asp Gln Val Ile Val Gln Arg Thr Leu Ala Ala Lys Asn Leu Ser His290 295 300Ala Lys Gly Gly Ala Leu Met Ala Ala Tyr Leu Lys Val Leu Pro Leu305 3l0 315 320Phe Ile Met Val Phe Pro Gly Met Val Ser Arg Ile Leu Phe Pro Asp325 330 335Gln Val Ala Cys Ala Asp Pro Glu Ile Cys Gln Lys Ile Cys Ser Asn340 345 350Pro Ser Gly Cys Ser Asp Ile Ala Tyr Pro Lys Leu Val Leu Glu Leu355 360 365Leu Pro Thr Gly Leu Arg Gly Leu Met Met Ala Val Met Val Ala Ala370 375 380Leu Met Ser Ser Leu Thr Ser Ile Phe Asn Ser Ala Ser Thr Ile Phe385 390 395 400Thr Met Asp Leu Trp Asn His Leu Arg Pro Arg Ala Ser Glu Lys Glu405 410 415Leu Met Ile Val Gly Arg Val Phe Val Leu Leu Leu Val Leu Val Ser420 425 430Ile Leu Trp Ile Pro Val Val Gln Ala Ser Gln Gly Gly Gln Leu Phe435 440 445Ile Tyr Ile Gln Ser Ile Ser Ser Tyr Leu Gln Pro Pro Val Ala Val450 455 460Val Phe Ile Met Gly Cys Phe Trp Lys Arg Thr Asn Glu Lys Gly Ala465 470 475 480Phe Trp Gly Leu Ile Ser Gly Leu Leu Leu Gly Leu Val Arg Leu Val485 490 495Leu Asp Phe Ile Tyr Val Gln Pro Arg Cys Asp Gln Pro Asp Glu Arg500 505 510Pro Val Leu Val Lys Ser Ile His Tyr Leu Tyr Phe Ser Met Ile Leu515 520 525Ser Thr Val Thr Leu Ile Thr Val Ser Thr Val Ser Trp Phe Thr Glu530 535 540Pro Pro Ser Lys Glu Met Val Ser His Leu Thr Trp Phe Thr Arg His545 550 555 560Asp Pro Val Val Gln Lys Glu Gln Ala Pro Pro Ala Ala Pro Leu Ser565 570 575Leu Thr Leu Ser Gln Asn Gly Met Pro Glu Ala Ser Ser Ser Ser Ser580 585 590Val Gln Phe Glu Met Val Gln Glu Asn Thr Ser Lys Thr His Ser Cys595 600 605Asp Met Thr Pro Lys Gln Ser Lys Val Val Lys Ala Ile Leu Trp Leu610 615 620Cys Gly Ile Gln Glu Lys Gly Lys Glu Glu Leu Pro Ala Arg Ala Glu625 630 635 640Ala Ile Ile Val Ser Leu Glu Glu Asn Pro Leu Val Lys Thr Leu Leu645 650 655Asp Val Asn Leu Ile Phe Cys Val Ser Cys Ala Ile Phe Ile Trp Gly660 665 670Tyr Phe Ala675<210>76<211>485<212>PRT<213>人(Homo sapiens)<400>76Met Glu Pro Cys Trp Gly Glu Gly Leu Phe His Leu Ala Pro Pro Arg1 5 10 15His His Pro Gln Lys Ala Asp Trp His Phe Cys Pro Gln His Ile Gln20 25 30Glu Phe Thr Asn Glu Thr Trp Gln Ala Arg Thr Gly Glu Pro Leu Pro35 40 45Asp His Leu Val Leu Leu Met Trp Ser Leu Ile Val Ser Leu Tyr Pro50 55 60Leu Gly Gly Leu Phe Gly Ala Leu Leu Ala Gly Pro Leu Ala Ile Thr65 70 75 80Leu Gly Arg Lys Lys Ser Leu Leu Val Asn Asn Ile Phe Val Val Ser85 90 95Ala Ala Ile Leu Phe Gly Phe Ser Arg Lys Ala Gly Ser Phe Glu Met100 105 110Ile Met Leu Gly Arg Leu Leu Val Gly Val Asn Ala Gly Val Ser Met115 120 125Asn Ile Gln Pro Met Tyr Leu Gly Glu Ser Ala Pro Lys Glu Leu Arg130 135 140Gly Ala Val Ala Met Ser Ser Ala Ile Phe Thr Ala Leu Gly Ile Val145 150 155 160Met Gly Gln Val Val Gly Leu Arg Glu Leu Leu Gly Gly Pro Gln Ala165 170 175Trp Pro Leu Leu Leu Ala Ser Cys Leu Val Pro Gly Ala Leu Gln Leu180 185 190Ala Ser Leu Pro Leu Leu Pro Glu Ser Pro Arg Tyr Leu Leu Ile Asp195 200 205Cys Gly Asp Thr Glu Ala Cys Leu Ala Ala Leu Arg Arg Leu Arg Gly210 215 220Ser Gly Asp Leu Ala Gly Glu Leu Glu Glu Leu Glu Glu Glu Arg Ala225 230 235 240Ala Cys Gln Gly Cys Arg Ala Arg Arg Pro Trp Glu Leu Phe Gln His245 250 255Arg Ala Leu Arg Arg Gln Val Thr Ser Leu Val Val Leu Gly Ser Ala260 265 270Met Glu Leu Cys Gly Asn Asp Ser Val Tyr Ala Tyr Ala Ser Ser Val275 280 285Phe Arg Lys Ala Gly Val Pro Glu Ala Lys Ile Gln Tyr Ala Ile Ile290 295 300Gly Thr Gly Ser Cys Glu Leu Leu Thr Ala Val Val Ser Cys Val Val305 310 315 320Ile Glu Arg Val Gly Arg Arg Val Leu Leu Ile Gly Gly Tyr Ser Leu325 330 335Met Thr Cys Trp Gly Ser Ile Phe Thr Val Ala Leu Cys Leu Gln Ser340 345 350Ser Phe Pro Trp Thr Leu Tyr Leu Ala Met Ala Cys Ile Phe Ala Phe355 360 365Ile Leu Ser Phe Gly Ile Gly Pro Ala Gly Val Thr Gly Ile Leu Ala370 375 380Thr Glu Leu Phe Asp Gln Met Ala Arg Pro Ala Ala Cys Met Val Cys385 390 395 400Gly Ala Leu Met Trp Ile Met Leu Ile Leu Val Gly Leu Gly Phe Pro405 410 415Phe Ile Met Glu Ala Leu Ser His Phe Leu Tyr Val Pro Phe Leu Gly420 425 430Val Cys Val Cys Gly Ala Ile Tyr Thr Gly Leu Phe Leu Pro Glu Thr435 440 445Lys Gly Lys Thr Phe Gln Glu Ile Ser Lys Glu Leu His Arg Leu Asn450 455 460Phe Pro Arg Arg Ala Gln Gly Pro Thr Trp Arg Ser Leu Glu Val Ile465 470 475 480Gln Ser Thr Glu Leu485<210>77<211>496<212>PRT<213>人(Homo sapiens)<400>77Met Arg Ala Leu Arg Arg Leu Ile Gln Gly Arg Ile Leu Leu Leu Thr1 5 10 15Ile Cys Ala Ala Gly Ile Gly Gly Thr Phe Gln Phe Gly Tyr Asn Leu20 25 30Ser Ile Ile Asn Ala Pro Thr Leu His Ile Gln Glu Phe Thr Asn Glu35 40 45Thr Trp Gln Ala Arg Thr Gly Glu Pro Leu Pro Asp His Leu Val Leu50 55 60Leu Met Trp Ser Leu Ile Val Ser Leu Tyr Pro Leu Gly Gly Leu Phe65 70 75 80Gly Ala Leu Leu Ala Gly Pro Leu Ala Ile Thr Leu Gly Arg Lys Lys85 90 95Ser Leu Leu Val Asn Asn Ile Phe Val Val Ser Ala Ala Ile Leu Phe100 105 110Gly Phe Ser Arg Lys Ala Gly Ser Phe Glu Met Ile Met Leu Gly Arg115 120 125Leu Leu Val Gly Val Asn Ala Gly Val Ser Met Asn Ile Gln Pro Met130 135 140Tyr Leu Gly Glu Ser Ala Pro Lys Glu Leu Arg Gly Ala Val Ala Met145 150 155 160Ser Ser Ala Ile Phe Thr Ala Leu Gly Ile Val Met Gly Gln Val Val165 170 175Gly Leu Arg Glu Leu Leu Gly Gly Pro Gln Ala Trp Pro Leu Leu Leu180 185 190Ala Ser Cys Leu Val Pro Gly Ala Leu Gln Leu Ala Ser Leu Pro Leu195 200 205Leu Pro Glu Ser Pro Arg Tyr Leu Leu Ile Asp Cys Gly Asp Thr Glu210 215 220Ala Cys Leu Ala Ala Leu Arg Arg Leu Arg Gly Ser Gly Asp Leu Ala225 230 235 240Gly Glu Leu Glu Glu Leu Glu Glu Glu Arg Ala Ala Cys Gln Gly Cys245 250 255Arg Ala Arg Arg Pro Trp Glu Leu Phe Gln Hi s Arg Ala Leu Arg Arg260 265 270Gln Val Thr Ser Leu Val Val Leu Gly Ser Ala Met Glu Leu Cys Gly275 280 285Asn Asp Ser Val Tyr Ala Tyr Ala Ser Ser Val Phe Arg Lys Ala Gly290 295 300Val Pro Glu Ala Lys Ile Gln Tyr Ala Ile Ile Gly Thr Gly Ser Cys305 310 315 320Glu Leu Leu Thr Ala Val Val Ser Cys Val Val Ile Glu Arg Val Gly325 330 335Arg Arg Val Leu Leu Ile Gly Gly Tyr Ser Leu Met Thr Cys Trp Gly340 345 350Ser Ile Phe Thr Val Ala Leu Cys Leu Gln Ser Ser Phe Pro Trp Thr355 360 365Leu Tyr Leu Ala Met Ala Cys Ile Phe Ala Phe Ile Leu Ser Phe Gly370 375 380Ile Gly Pro Ala Gly Val Thr Gly Ile Leu Ala Thr Glu Leu Phe Asp385 390 395 400Gln Met Ala Arg Pro Ala Ala Cys Met Val Cys Gly Ala Leu Met Trp405 410 415Ile Met Leu Ile Leu Val Gly Leu Gly Phe Pro Phe Ile Met Glu Ala420 425 430Leu Ser His Phe Leu Tyr Val Pro Phe Leu Gly Val Cys Val Cys Gly435 440 445Ala Ile Tyr Thr Gly Leu Phe Leu Pro Glu Thr Lys Gly Lys Thr Phe450 455 460Gln Glu Ile Ser Lys Glu Leu His Arg Leu Asn Phe Pro Arg Arg Ala465 470 475 480Gln Gly Pro Thr Trp Arg Ser Leu Glu Val Ile Gln Ser Thr Glu Leu485 490 495<210>78<211>500<212>PRT<213>人(Homo sapiens)<400>78Asx Met Leu His Ala Leu Leu Arg Ser Arg Met Ile Gln Gly Arg Ile1 5 10 15Leu Leu Leu Thr Ile Cys Ala Ala Gly Ile Gly Gly Thr Phe Gln Phe20 25 30Gly Tyr Asn Leu Ser Ile Ile Asn Ala Pro Thr Leu His Ile Gln Glu35 40 45Phe Thr Asn Glu Thr Trp Gln Ala Arg Thr Gly Glu Pro Leu Pro Asp50 55 60His Leu Val Leu Leu Met Trp Ser Leu Ile Val Ser Leu Tyr Pro Leu65 70 75 80Gly Gly Leu Phe Gly Ala Leu Leu Ala Gly Pro Leu Ala Ile Thr Leu85 90 95Gly Arg Lys Lys Ser Leu Leu Val Asn Asn Ile Phe Val Val Ser Ala100 105 110Ala Ile Leu Phe Gly Phe Ser Arg Lys Ala Gly Ser Phe Glu Met Ile115 120 125Met Leu Gly Arg Leu Leu Val Gly Val Asn Ala Gly Val Ser Met Asn130 135 140Ile Gln Pro Met Tyr Leu Gly Glu Ser Ala Pro Lys Glu Leu Arg Gly145 150 155 160Ala Val Ala Met Ser Ser Ala Ile Phe Thr Ala Leu Gly Ile Val Met165 170 175Gly Gln Val Val Gly Leu Arg Glu Leu Leu Gly Gly Pro Gln Ala Trp180 185 190Pro Leu Leu Leu Ala Ser Cys Leu Val Pro Gly Ala Leu Gln Leu Ala195 200 205Ser Leu Pro Leu Leu Pro Glu Ser Pro Arg Tyr Leu Leu Ile Asp Cys210 215 220Gly Asp Thr Glu Ala Cys Leu Ala Ala Leu Arg Arg Leu Arg Gly Ser225 230 235 240Gly Asp Leu Ala Gly Glu Leu Glu Glu Leu Glu Glu Glu Arg Ala Ala245 250 255Cys Gln Gly Cys Arg Ala Arg Arg Pro Trp Glu Leu Phe Gln His Arg260 265 270Ala Leu Arg Arg Gln Val Thr Ser Leu Val Val Leu Gly Ser Ala Met275 280 285Glu Leu Cys Gly Asn Asp Ser Val Tyr Ala Tyr Ala Ser Ser Val Phe290 295 300Arg Lys Ala Gly Val Pro Glu Ala Lys Ile Gln Tyr Ala Ile Ile Gly305 310 315 320Thr Gly Ser Cys Glu Leu Leu Thr Ala Val Val Ser Cys Val Val Ile325 330 335Glu Arg Val Gly Arg Arg Val Leu Leu Ile Gly Gly Tyr Ser Leu Met340 345 350Thr Cys Trp Gly Ser Ile Phe Thr Val Ala Leu Cys Leu Gln Ser Ser355 360 365Phe Pro Trp Thr Leu Tyr Leu Ala Met Ala Cys Ile Phe Ala Phe Ile370 375 380Leu Ser Phe Gly Ile Gly Pro Ala Gly Val Thr Gly Ile Leu Ala Thr385 390 395 400Glu Leu Phe Asp Gln Met Ala Arg Pro Ala Ala Cys Met Val Cys Gly405 410 415Ala Leu Met Trp Ile Met Leu Ile Leu Val Gly Leu Gly Phe Pro Phe420 425 430Ile Met Glu Ala Leu Ser His Phe Leu Tyr Val Pro Phe Leu Gly Val435 440 445Cys Val Cys Gly Ala Ile Tyr Thr Gly Leu Phe Leu Pro Glu Thr Lys450 455 460Gly Lys Thr Phe Gln Glu Ile Ser Lys Glu Leu His Arg Leu Asn Phe465 470 475 480Pro Arg Arg Ala Gln Gly Pro Thr Trp Arg Ser Leu Glu Val Ile Gln485 490 495Ser Thr Glu Leu500<210>79<211>1358<212>PRT<213>人(Homo sapiens)<400>79Met Val Val Val Lys Pro Met Asn Thr Met Ala Pro Val Val Thr Arg1 5 10 15Asn Thr Gly Leu Ile Leu Tyr Glu Gly Gln Ser Arg Pro Leu Thr Gly20 25 30Pro Ala Gly Ser Gly Pro Gln Asn Leu Val Ile Ser Asp Glu Asp Asp35 40 45Leu Glu Ala Val Arg Leu Glu Val Val Ala Gly Leu Arg His Gly His50 55 60Leu Val Ile Leu Gly Ala Ser Ser Gly Ser Ser Ala Pro Lys Ser Phe65 70 75 80Thr Val Ala Glu Leu Ala Ala Gly Gln Val Val Tyr Gln His Asp Asp85 90 95Arg Asp Gly Ser Leu Ser Asp Asn Leu Val Leu Arg Met Val Asp Gly100 105 1l0Gly Gly Arg His Gln Val Gln Phe Leu Phe Pro Ile Thr Leu Val Pro115 120 125Val Asp Asp Gln Pro Pro Val Leu Asn Ala Asn Thr Gly Leu Thr Leu130 135 140Ala Glu Gly Glu Thr Val Pro Ile Leu Pro Leu Ser Leu Ser Ala Thr145 150 155 160Asp Met Asp Ser Asp Asp Ser Leu Leu Leu Phe Val Leu Glu Ser Pro165 170 175Phe Leu Thr Thr Gly His Leu Leu Leu Arg Gln Thr His Pro Pro His180 185 190Glu Lys Gln Glu Leu Leu Arg Gly Leu Trp Arg Lys Glu Gly Ala Phe195 200 205Tyr Glu Arg Thr Val Thr Glu Trp Gln Gln Gln Asp Ile Thr Glu Gly210 215 220Arg Leu Phe Tyr Arg His Ser Gly Pro His Ser Pro Gly Pro Val Thr225 230 235 240Asp Gln Phe Thr Phe Arg Val Gln Asp Asn His Asp Pro Pro Asn Gln245 250 255Ser Gly Leu Gln Arg Phe Val Ile Arg Ile His Pro Val Asp Arg Leu260 265 270Pro Pro Glu Leu Gly Ser Gly Cys Pro Leu Arg Met Val Val Gln Glu275 280 285Ser Gln Leu Thr Pro Leu Arg Lys Lys Trp Leu Arg Tyr Thr Asp Leu290 295 300Asp Thr Asp Asp Arg Glu Leu Arg Tyr Thr Val Thr Gln Ser Pro Thr305 310 315 320Asp Thr Asp Glu Asn His Leu Pro Ala Pro Leu Gly Thr Leu Val Leu325 330 335Thr Asp Asn Pro Ser Val Val Val Thr His Phe Thr Gln Ala Gln Ile340 345 350Asn His His Lys Ile Ala Tyr Arg Pro Pro Gly Gln Glu Leu Gly Val355 360 365Ala Thr Arg Val Ala Gln Phe Gln Phe Gln Val Glu Asp Arg Ala Gly370 375 380Asn Val Ala Pro Gly Thr Phe Thr Leu Tyr Leu His Pro Val Asp Asn385 390 395 400Gln Pro Pro Glu Ile Leu Asn Thr Gly Phe Thr Ile Gln Glu Lys Gly405 410 415His His Ile Leu Ser Glu Thr Glu Leu His Val Asn Asp Val Asp Thr420 425 430Asp Val Ala His Ile Ser Phe Thr Leu Thr Gln Ala Pro Lys His Gly435 440 445His Met Arg Val Ser Gly Gln Ile Leu His Val Gly Gly Leu Phe His450 455 460Leu Glu Asp Ile Lys Gln Gly Arg Val Ser Tyr Ala His Asn Gly Asp465 470 475 480Lys Ser Leu Thr Asp Ser Cys Ser Leu Glu Val Ser Asp Arg His His485 490 495Val Val Pro Ile Thr Leu Arg Val Asn Val Arg Pro Val Asp Asp Glu500 505 510Val Pro Ile Leu Ser His Pro Thr Gly Thr Leu Glu Ser Tyr Leu Asp515 520 525Val Leu Glu Asn Gly Ala Thr Glu Ile Thr Ala Asn Val Ile Lys Gly530 535 540Thr Asn Glu Glu Thr Asp Asp Leu Met Leu Thr Phe Leu Leu Glu Asp545 550 555 560Pro Pro Leu Tyr Gly Glu Ile Leu Val Asn Gly Ile Pro Ala Glu Gln565 570 575Phe Thr Gln Arg Asp Ile Leu Glu Gly Ser Val Val Tyr Thr His Thr580 585 590Ser Gly Glu Ile Gly Leu Leu Pro Lys Ala Asp Ser Phe Asn Leu Ser595 600 605Leu Ser Asp Met Ser Gln Glu Trp Arg Ile Gly Gly Asn Thr Ile Gln610 615 620Gly Val Thr Ile Trp Val Thr Ile Leu Pro Val Asp Ser Gln Ala Pro625 630 635 640Glu Ile Phe Val Gly Glu Gln Leu Ile Val Met Glu Gly Asp Lys Ser645 650 655Val Ile Thr Ser Val His Ile Ser Ala Glu Asp Val Asp Ser Leu Asn660 665 670Asp Asp Ile Leu Cys Thr Ile Val Ile Gln Pro Thr Ser Gly Tyr Val675 680 685Glu Asn Ile Ser Pro Ala Pro Gly Ser Glu Lys Ser Arg Ala Gly Ile690 695 700Ala Ile Ser Ala Phe Asn Leu Lys Asp Leu Arg Gln Gly His Ile Asn705 710 715 720Tyr Val Gln Ser Val His Lys Gly Val Glu Pro Val Glu Asp Arg Phe725 730 735Val Phe Arg Cys Ser Asp Gly Ile Asn Phe Ser Glu Arg Gln Phe Phe740 745 750Pro Ile Val Ile Ile Pro Thr Asn Asp Glu Gln Pro Glu Met Phe Met755 760 765Arg Glu Phe Met Val Met Glu Gly Met Ser Leu Val Ile Asp Thr Pro770 775 780Ile Leu Asn Ala Ala Asp Ala Asp Val Pro Leu Asp Asp Leu Thr Phe785 790 795 800Thr Ile Thr Gln Phe Pro Thr His Gly His Ile Met Asn Gln Leu Ile805 810 815Asn Gly Thr Val Leu Val Glu Ser Phe Thr Leu Asp Gln Ile Ile Glu820 825 830Ser Ser Ser Ile Ile Tyr Glu His Asp Asp Ser Glu Thr Gln Glu Asp835 840 845Ser Phe Val Ile Lys Leu Thr Asp Gly Lys His Ser Val Glu Lys Thr850 855 860Val Leu Ile Ile Val Ile Pro Val Asp Asp Glu Thr Pro Arg Met Thr865 870 875 880Ile Asn Asn Gly Leu Glu Ile Glu Ile Gly Asp Thr Lys Ile Ile Asn885 890 895Asn Lys Ile Leu Met Ala Thr Asp Leu Asp Ser Glu Asp Lys Ser Leu900 905 910Val Tyr Ile Ile Arg Tyr Gly Pro Gly His Gly Leu Leu Gln Arg Arg915 920 925Lys Pro Thr Gly Ala Phe Glu Asn Ile Thr Leu Gly Met Asn Phe Thr930 935 940Gln Asp Glu Val Asp Arg Asn Leu Ile Gln Tyr Val His Leu Gly Gln945 950 955 960Glu Gly Ile Arg Asp Leu Ile Lys Phe Asp Val Thr Asp Gly Ile Asn965 970 975Pro Leu Ile Asp Arg Tyr Phe Tyr Val Ser Ile Gly Ser Ile Asp Ile980 985 990Val Phe Pro Asp Val Ile Ser Lys Gly Val Ser Leu Lys Glu Gly Gly995 10001005Lys Val Thr Leu Thr Thr Asp Leu Leu Ser Thr Ser Asp Leu Asn Ser101010151020Pro Asp Glu Asn Leu Val Phe Thr Ile Thr Arg Ala Pro Met Arg Gly1025103010351040His Leu Glu Cys Thr Asp Gln Pro Gly Val Ser Ile Thr Ser Phe Thr104510501055Gln Leu Gln Leu Ala Gly Asn Lys Ile Tyr Tyr Ile His Thr Ala Asp106010651070Asp Glu Val Lys Met Asp Ser Phe Glu Phe Gln Val Thr Asp Gly Arg107510801085Asn Pro Val Phe Arg Thr Phe Arg Ile Ser Ile Ser Asp Val Asp Asn109010951100Lys Lys Pro Val Val Thr Ile His Lys Leu Val Val Ser Glu Ser Glu1105111011151120Asn Lys Leu Ile Thr Pro Phe Glu Leu Thr Val Glu Asp Arg Asp Thr112511301135Pro Asp Ly s Leu Leu Lys Phe Thr Ile Thr Gln Val Pro Ile His Gly114011451150His Leu Leu Phe Asn Asn Thr Arg Pro Val Met Val Phe Thr Lys Gln115511601165Asp Leu Asn Glu Asn Leu Ile Ser Tyr Lys His Asp Gly Thr Glu Ser117011751180Ser Glu Asp Ser Phe Ser Phe Thr Val Thr Asp Gly Thr His Thr Asp1185119011951200Phe Tyr Val Phe Pro Asp Thr Val Phe Glu Thr Arg Arg Pro Gln Val120512101215Met Lys Ile Gln Val Leu Ala Val Asp Asn Ser Val Pro Gln Ile Ala122012251230Val Asn Lys Gly Ala Ser Thr Leu Arg Thr Leu Ala Thr Gly His Leu123512401245Gly Phe Met Ile Thr Ser Lys Ile Leu Lys Val Glu Asp Arg Asp Ser125012551260Leu His Ile Ser Leu Arg Phe Ile Val Thr Glu Ala Pro Gln His Gly1265127012751280Tyr Leu Leu Asn Leu Asp Lys Gly Asn His Ser Ile Thr Gln Phe Thr128512901295Gln Ala Asp Ile Asp Asp Met Lys Ile Cys Tyr Val Leu Arg Glu Gly130013051310Ala Asn Ala Thr Ser Asp Met Phe Tyr Phe Ala Val Glu Asp Gly Gly131513201325Lys Tyr Ser Pro Leu Leu Val Val Thr Ala Arg Arg Asp Ala Phe Leu133013351340Gly Cys Ser Leu Met Thr Leu Leu Gln Glu Val Phe Ile Lys134513501355<210>80<211>3105<212>PRT<213>人(Homo sapiens)<400>80Met Ala Arg Ser Trp Leu Thr Ala Thr Ser Thr Ser Arg Pro Ala Ala1 5 10 15Phe Gly Arg Ala Leu Leu Ser Pro Gly Leu Ala Gly Ala Ala Gly Val20 25 30Pro Ala Glu Glu Ala Ile Val Leu Ala Asn Arg Gly Leu Arg Val Pro35 40 45Phe Gly Arg Glu Val Trp Leu Asp Pro Leu His Asp Leu Val Leu Gln50 55 60Val Gln Pro Gly Asp Arg Cys Ala Val Ser Val Leu Asp Asn Asp Ala65 70 75 80Leu Ala Gln Arg Pro Gly Arg Leu Ser Pro Lys Arg Phe Pro Cys Asp85 90 95Phe Gly Pro Gly Glu Val Arg Tyr Ser His Leu Gly Ala Arg Ser Pro100 105 110Ser Arg Asp Arg Val Arg Leu Gln Leu Arg Tyr Asp Ala Pro Gly Gly115 120 125Ala Val Val Leu Pro Leu Val Leu Glu Val Glu Val Val Phe Thr Gln130 135 140Leu Glu Val Val Thr Arg Asn Leu Pro Leu Val Val Glu Glu Leu Leu145 150 155 160Gly Thr Ser Asn Ala Leu Asp Ala Arg Ser Leu Glu Phe Ala Phe Gln165 170 175Pro Glu Thr Glu Glu Cys Arg Val Gly Ile Leu Ser Gly Leu Gly Ala180 185 190Leu Pro Arg Tyr Gly Glu Leu Leu His Tyr Pro Gln Val Pro Gly Gly195 200 205Ala Arg Glu Gly Gly Ala Pro Glu Thr Leu Leu Met Asp Cys Lys Ala210 215 220Phe Gln Glu Leu Gly Val Arg Tyr Arg His Thr Ala Ala Ser Arg Ser225 230 235 240Pro Asn Arg Asp Trp Ile Pro Met Val Val Glu Leu Arg Ser Arg Gly245 250 255Ala Pro Val Gly Ser Pro Ala Leu Lys Arg Glu His Phe Gln Val Leu260 265 270Val Arg Ile Arg Gly Gly Ala Glu Asn Thr Ala Pro Lys Pro Ser Phe275 280 285Val Ala Met Met Met Met Glu Val Asp Gln Phe Val Leu Thr Ala Leu290 295 300Thr Pro Asp Met Leu Ala Ala Glu Asp Ala Glu Ser Pro Ser Asp Leu305 310 315 320Leu Ile Phe Asn Leu Thr Ser Pro Phe Gln Pro Gly Gln Gly Tyr Leu325 330 335Val Ser Thr Asp Asp Arg Ser Leu Pro Leu Ser Ser Phe Thr Gln Arg340 345 350Asp Leu Arg Leu Leu Lys Ile Ala Tyr Gln Pro Pro Ser Glu Asp Ser355 360 365Asp Gln Glu Arg Leu Phe Glu Leu Glu Leu Glu Val Val Asp Leu Glu370 375 380Gly Ala Ala Ser Asp Pro Phe Ala Phe Met Val Val Val Lys Pro Met385 390 395 400Asn Thr Met Ala Pro Val Val Thr Arg Asn Thr Gly Leu Ile Leu Tyr405 410 4l5Glu Gly Gln Ser Arg Pro Leu Thr Gly Pro Ala Gly Ser Gly Pro Gln420 425 430Asn Leu Val Ile Ser Asp Glu Asp Asp Leu Glu Ala Val Arg Leu Glu435 440 445Val Val Ala Gly Leu Arg His Gly His Leu Val Ile Leu Gly Ala Ser450 455 460Ser Gly Ser Ser Ala Pro Lys Ser Phe Thr Val Ala Glu Leu Ala Ala465 470 475 480Gly Gln Val Val Tyr Gln His Asp Asp Arg Asp Gly Ser Leu Ser Asp485 490 495Asn Leu Val Leu Arg Met Val Asp Gly Gly Gly Arg His Gln Val Gln500 505 510Phe Leu Phe Pro Ile Thr Leu Val Pro Val Asp Asp Gln Pro Pro Val515 520 525Leu Asn Ala Asn Thr Gly Leu Thr Leu Ala Glu Gly Glu Thr Val Pro530 535 540Ile Leu Pro Leu Ser Leu Ser Ala Thr Asp Met Asp Ser Asp Asp Ser545 550 555 560Leu Leu Leu Phe Val Leu Glu Ser Pro Phe Leu Thr Thr Gly His Leu565 570 575Leu Leu Arg Gln Thr His Pro Pro His Glu Lys Gln Glu Leu Leu Arg580 585 590Gly Leu Trp Arg Lys Glu Gly Ala Phe Tyr Glu Arg Thr Val Thr Glu595 600 605Trp Gln Gln Gln Asp Ile Thr Glu Gly Arg Leu Phe Tyr Arg His Ser6l0 615 620Gly Pro His Ser Pro Gly Pro Val Thr Asp Gln Phe Thr Phe Arg Val625 630 635 640Gln Asp Asn His Asp Pro Pro Asn Gln Ser Gly Leu Gln Arg Phe Val645 650 655Ile Arg Ile His Pro Val Asp Arg Leu Pro Pro Glu Leu Gly Ser Gly660 665 670Cys Pro Leu Arg Met Val Val Gln Glu Ser Gln Leu Thr Pro Leu Arg675 680 685Lys Lys Trp Leu Arg Tyr Thr Asp Leu Asp Thr Asp Asp Arg Glu Leu690 695 700Arg Tyr Thr Val Thr Gln Pro Pro Thr Asp Thr Asp Glu Asn His Leu705 710 715 720Pro Ala Pro Leu Gly Thr Leu Val Leu Thr Asp Asn Pro Ser Val Val725 730 735Val Thr His Phe Thr Gln Ala Gln Ile Asn His His Lys Ile Ala Tyr740 745 750Arg Pro Pro Gly Gln Glu Leu Gly Val Ala Thr Arg Val Ala Gln Phe755 760 765Gln Phe Gln Val Glu Asp Arg Ala Gly Asn Val Ala Pro Gly Thr Phe770 775 780Thr Leu Tyr Leu His Pro Val Asp Asn Gln Pro Pro Glu Ile Leu Asn785 790 795 800Thr Gly Phe Thr Ile Gln Glu Lys Gly His His Ile Leu Ser Glu Thr805 810 815Glu Leu His Val Asn Asp Val Asp Thr Asp Val Ala His Ile Ser Phe820 825 830Thr Leu Thr Gln Ala Pro Lys His Gly His Met Arg Val Ser Gly Gln835 840 845Ile Leu His Val Gly Gly Leu Phe His Leu Glu Asp Ile Lys Gln Gly850 855 860Arg Val Ser Tyr Ala His Asn Gly Asp Lys Ser Leu Thr Asp Ser Cys865 870 875 880Ser Leu Glu Val Ser Asp Arg His His Val Val Pro Ile Thr Leu Arg885 890 895Val Asn Val Arg Pro Val Asp Asp Glu Val Pro Ile Leu Ser His Pro900 905 910Thr Gly Thr Leu Glu Ser Tyr Leu Asp Val Leu Glu Asn Gly Ala Thr915 920 925Glu Ile Thr Ala Asn Val Ile Lys Gly Thr Asn Glu Glu Thr Asp Asp930 935 940Leu Met Leu Thr Phe Leu Leu Glu Asp Pro Pro Leu Tyr Gly Glu Ile945 950 955 960Leu Val Asn Gly Ile Pro Ala Glu Gln Phe Thr Gln Arg Asp Ile Leu965 970 975Glu Gly Ser Val Val Tyr Thr His Thr Ser Gly Glu Ile Gly Leu Leu980 985 990Pro Lys Ala Asp Ser Phe Asn Leu Ser Leu Ser Asp Lys Ser Gln Glu995 10001005Trp Arg Ile Gly Gly Asn Thr Ile Gln Gly Val Thr Ile Trp Val Thr101010151020Ile Leu Pro Val Asp Ser Gln Ala Pro Glu Ile Ser Val Gly Glu Glnl025103010351040Leu Ile Val Met Glu Gly Asp Lys Ser Val Ile Thr Ser Val His Ile104510501055Ser Ala Glu Asp Val Asp Ser Leu Asn Asp Asp Ile Leu Cys Thr Ile106010651070Val Ile Gln Pro Thr Ser Gly Tyr Val Glu Asn Ile Ser Pro Ala Pro107510801085Gly Ser Glu Lys Ser Arg Ala Gly Ile Ala Ile Ser Ala Phe Asn Leu109010951100Lys Asp Leu Arg Gln Gly His Ile Asn Tyr Val Gln Ser Val His Lys1105111011151120Gly Val Glu Pro Val Glu Asp Arg Phe Val Phe Arg Cys Ser Asp Gly112511301135Ile Asn Phe Ser Glu Arg Gln Phe Phe Pro Ile Val Ile Ile Pro Thr114011451150Asn Asp Glu Gln Pro Glu Met Phe Met Arg Glu Phe Met Val Met Glu115511601165Gly Met Ser Leu Val Ile Asp Thr Pro Ile Leu Asn Ala Ala Asp Ala117011751180Asp Val Pro Leu Asp Asp Leu Thr Phe Thr Ile Thr Gln Phe Pro Thr1185119011951200His Gly His Ile Met Asn Gln Leu Ile Asn Gly Thr Val Leu Val Glu120512101215Ser Phe Thr Leu Asp Gln Ile Ile Glu Ser Ser Ser Ile Ile Tyr Glu122012251230His Asp Asp Ser Glu Thr Gln Glu Asp Ser Phe Val Ile Lys Leu Thr123512401245Asp Gly Lys His Ser Val Glu Lys Thr Val Leu Ile Ile Val Ile Pro125012551260Val Asp Asp Glu Thr Pro Arg Met Thr Ile Asn Asn Gly Leu Glu Ile1265127012751280Glu Ile Gly Asp Thr Lys Ile Ile Asn Asn Lys Ile Leu Met Ala Thr128512901295Asp Leu Asp Ser Glu Asp Lys Ser Leu Val Tyr Ile Ile Arg Tyr Gly130013051310Pro Gly His Gly Leu Leu Gln Arg Arg Lys Pro Thr Gly Ala Phe Glu131513201325Asn Ile Thr Leu Gly Met Asn Phe Thr Gln Asp Glu Val Asp Arg Asn133013351340Leu Ile Gln Tyr Val His Leu Gly Gln Glu Gly Ile Arg Asp Leu Ile1345135013551360Lys Phe Asp Val Thr Asp Gly Ile Asn Pro Leu Ile Asp Arg Tyr Phe136513701375Tyr Val Ser Ile Gly Ser Ile Asp Ile Val Phe Pro Asp Val Ile Ser138013851390Lys Gly Val Ser Leu Lys Glu Gly Gly Lys Val Thr Leu Thr Thr Asp139514001405Leu Leu Ser Thr Ser Asp Leu Asn Ser Pro Asp Glu Asn Leu Val Phe141014151420Thr Ile Thr Arg Ala Pro Met Arg Gly His Leu Glu Cys ThrAsp Gln1425143014351440Pro Gly Val Ser Ile Thr Ser Phe Thr Gln Leu Gln Leu Ala Gly Asn144514501455Lys Ile Tyr Tyr Ile His Thr Ala Asp Asp Glu Val Lys Met Asp Ser146014651470Phe Glu Phe Gln Val Thr Asp Gly Arg Asn Pro Val Phe Arg Thr Phe147514801485Arg Ile Ser Ile Ser Asp Val Asp Asn Lys Lys Pro Val Val Thr Ilel49014951500His Lys Leu Val Val Ser Glu Ser Glu Asn Lys Leu Ile Thr Pro Phe1505151015151520Glu Leu Thr Val Glu Asp Arg Asp Thr Pro Asp Lys Leu Leu Lys Phe152515301535Thr Ile Thr Gln Val Pro Ile His Gly His Leu Leu Phe Asn Asn Thr154015451550Arg Pro Val Met Val Phe Thr Lys Gln Asp Leu Asn Glu Asn Leu Ile155515601565Ser Tyr Lys His Asp Gly Thr Glu Ser Ser Glu Asp Ser Phe Ser Phe157015751580Thr Val Thr Asp Gly Thr His Thr Asp Phe Tyr Val Phe Pro Asp Thr1585159015951600Val Phe Glu Thr Arg Arg Pro Gln Val Met Lys Ile Gln Val Leu Ala160516101615Val Asp Asn Ser Val Pro Gln Ile Ala Val Asn Lys Gly Ala Ser Thr162016251630Leu Arg Thr Leu Ala Thr Gly His Leu Gly Phe Met Ile Thr Ser Lys163516401645Ile Leu Lys Val Glu Asp Arg Asp Ser Leu His Ile Ser Leu Arg Phe165016551660Ile Val Thr Glu Ala Pro Gln His Gly Tyr Leu Leu Asn Leu Asp Lys1665167016751680Gly Asn His Ser Ile Thr Gln Phe Thr Gln Ala Asp Ile Asp Asp Met168516901695Lys Ile Cys Tyr Val Leu Arg Glu Gly Ala Asn Ala Thr Ser Asp Met170017051710Phe Tyr Phe Ala Val Glu Asp Gly Gly Gly Asn Lys Leu Thr Tyr Gln171517201725Asn Phe Arg Leu Asn Trp Ala Trp Ile Ser Phe Glu Lys Glu Tyr Tyr173017351740Leu Val Asn Glu Asp Ser Lys Phe Leu Asp Val Val Leu Lys Arg Arg1745175017551760Gly Tyr Leu Gly Glu Thr Ser Phe Ile Ser Ile Gly Thr Arg Asp Arg176517701775Thr Ala Glu Lys Asp Lys Asp Phe Lys Gly Lys Ala Gln Lys Gln Val178017851790Gln Phe Asn Pro Gly Gln Thr Arg Ala Thr Trp Arg Val Arg Ile Leu179518001805Ser Asp Gly Glu His Glu Gln Ser Glu Thr Phe Gln Val Val Leu Ser181018151820Glu Pro Val Leu Ala Ala Leu Glu Phe Pro Thr Val Ala Thr Val Glu1825183018351840Ile Val Asp Pro Gly Asp Glu Pro Thr Val Phe Ile Pro Gln Ser Lys184518501855Tyr Ser Val Glu Glu Asp Val Gly Glu Leu Phe Ile Pro Ile Arg Arg186018651870Ser Gly Asp Val Ser Gln Glu Leu Met Val Val Cys Tyr Thr Gln Gln187518801885Gly Thr Ala Thr Gly Thr Val Pro Thr Ser Val Leu Ser Tyr Ser Asp189018951900Tyr Ile Ser Arg Pro Glu Asp His Thr Ser Val Val Arg Phe Asp Lys1905191019151920Asp Glu Arg Glu Lys Leu Cys Arg Ile Val Ile Ile Asp Asp Ser Leu192519301935Tyr Glu Glu Glu Glu Thr Phe His Val Leu Leu Ser Met Pro Met Gly194019451950Gly Arg Ile Gly Ser Glu Phe Pro Gly Ala Gln Val Thr Ile Val Pro195519601965Asp Lys Asp Asp Gly Pro Ser Asp Ser Lys Phe Asn Val Ala Glu Asn197019751980Tyr Ser Leu Leu Pro Phe Thr Cys Phe Gln Gly Ser Ile Ala Thr Ala1985199019952000Glu Ala Ala Thr Gln Gly Gly Gly Arg Ser Thr Arg Gln Val Ala Ala200520102015Val Lys Lys Asp Lys Asp Phe Lys Gly Lys Ala Gln Lys Gln Val Gln202020252030Phe Asn Pro Gly Gln Thr Arg Ala Thr Trp Arg Val Arg Ile Leu Ser203520402045Asp Gly Glu His Glu Gln Ser Glu Thr Phe Gln Val Val Leu Ser Glu205020552060Pro Val Leu Ala Ala Leu Glu Phe Pro Thr Val Ala Thr Val Glu Ile2065207020752080Val Asp Pro Gly Asp Ala Cys Pro Trp Gly Glu Glu Ser Asp Gln Ser208520902095Ser Gln Gly Leu Lys Leu Gln Ser Phe Leu Thr Lys Met Met Val Ser210021052110Thr Asn Leu Leu Glu Asn Ser Phe Ser Arg Glu Asp Gln His Gln Glu211521202125Gln Leu Ser Arg Gln Lys Lys Trp Glu Ser Lys Thr Met Ile Ile Tyr213021352140Thr Phe Ile Leu Cys Glu Thr Glu Lys Pro Cys Ile Leu Glu Leu Met214521502155 2160Asp Asp Val Leu Tyr Glu Glu Val Glu Glu Leu Arg Leu Val Leu Gly216521702175Thr Pro Gln Ser Asn Ser Pro Phe Gly Ala Ala Val Gly Glu Gln Asn218021852190Glu Thr Leu Ile Arg Ile Arg Asp Asp Ala Asp Lys Thr Val Ile Lys219522002205Phe Gly Glu Thr Lys Phe Ser Val Thr Glu Pro Lys Glu Pro Gly Glu221022152220Ser Val Val Ile Arg Ile Pro Val Ile Arg Gln Gly Asp Thr Ser Lys2225223022352240Val Ser Ile Val Arg Val His Thr Lys Asp Gly Ser Ala Thr Ser Gly224522502255Glu Asp Tyr His Pro Val Ser Glu Glu Ile Glu Phe Lys Glu Gly Glu226022652270Thr Gln His Val Val Glu Ile Glu Val Thr Phe Asp Gly Val Arg Glu227522802285Met Arg Glu Ala Phe Thr Val His Leu Lys Pro Asp Glu Asn Met Ile229022952300Ala Glu Met Gln Leu Ser Asn Phe Glu Leu Thr Leu Ser Pro Asp Gly2305231023152320Thr Arg Val Gly Asn His Lys Cys Ser Asn Leu Leu Asp Tyr Thr Glu232523302335Val Lys Thr His Tyr Gly Phe Leu Thr Asp Ala Thr Lys Asn Pro Glu234023452350Ile Ile Gly Glu Thr Tyr Pro Tyr Gln Tyr Ser Leu Ser Ile Arg Gly235523602365Ser Thr Thr Leu Arg Phe Tyr Arg Asn Leu Asn Leu Glu Ala Cys Leu237023752380Trp Glu Phe Val Ser Tyr Tyr Asp Met Ser Glu Leu Leu Ala Asp Cys2385239023952400Arg Ser Val Leu Asn Ala Ser Ile Phe His Glu Met Ala Pro Glu Gly240524102415Lys Gln Ser Lys Cys Leu Val Asn Ser Thr Leu Tyr Ser Ile Leu Glu242024252430Cys His Glu Ser Leu Pro Asn Phe Cys Ile Ser Ala Leu Arg Met Gly243524402445Lys Trp Arg Lys Ile Lys Ser Lys Pro Ser Ala Gln Thr Pro Cys Ala245024552460Gln Arg Leu Arg Gly Phe Ile Asp His Pro Arg Lys Gln Pro Leu Gln2465247024752480Gln Ala Ser Ala Asp Pro Gly Met Leu Pro Val Ile Ser Thr Arg Glu248524902495Leu Ser Asn Phe Glu Leu Thr Leu Ser Pro Asp Gly Thr Arg Val Gly250025052510Asn His Lys Cys Ser Asn Leu Leu Asp Tyr Thr Glu Val Lys Thr His251525202525Tyr Gly Phe Leu Thr Asp Ala Thr Lys Asn Pro Glu Ile Ile Gly Glu253025352540Thr Tyr Pro Tyr Gln Tyr Ser Leu Ser Ile Arg Gly Ser Thr Thr Leu2545255025552560Arg Phe Tyr Arg Asn Leu Asn Leu Glu Ala Cys Leu Trp Glu Phe Val256525702575Ser Tyr Tyr Asp Met Ser Glu Leu Leu Ala Asp Cys Gly Gly Thr Ile258025852590Gly Thr Asp Gly Gln Val Leu Asn Leu Val Gln Ser Tyr Val Thr Leu259526002605Arg Val Pro Leu Tyr Val Ser Tyr Val Phe His Ser Pro Val Gly Val261026152620Gly Gly Trp Gln His Phe Asp Leu Lys Ser Glu Leu Arg Leu Thr Phe2625263026352640Val Tyr Asp Thr Ala Ile Leu Trp Asn Asp Gly Ile Gly Ser Pro Pro264526502655Glu Ala Glu Leu Gln Gly Ser Leu Tyr Pro Thr Ser Met Arg Ile Gly266026652670Asp Glu Gly Arg Leu Ala Val His Phe Lys Thr Glu Ala Gln Phe His267526802685Gly Leu Phe Val Leu Ser His Pro Ala Ser Phe Thr Ser Ser Val Ile269026952700Met Ser Ala Asp His Pro Gly Leu Thr Phe Ser Leu Arg Leu Ile Arg2705271027152720Ser Glu Pro Thr Tyr Asn Gln Pro Val Gln Gln Trp Ser Phe Val Ser272527302735Asp Phe Ala Val Arg Asp Tyr Ser Gly Thr Tyr Thr Val Lys Leu Val274027452750Pro Cys Thr Ala Pro Ser His Gln Glu Tyr Arg Leu Pro Val Thr Cys275527602765Asn Pro Arg Glu Pro Val Thr Phe Asp Leu Asp Ile Arg Phe Gln Gln277027752780Val Ser Asp Pro Val Ala Ala Glu Phe Ser Leu Asn Thr Gln Met Tyr2785279027952800Leu Leu Ser Lys Lys Ser Leu Trp Leu Ser Asp Gly Ser Met Gly Phe280528102815Gly Gln Glu Ser Asp Val Ala Phe Ala Glu Gly Asp Ile Ile Tyr Gly282028252830Arg Val Met Val Asp Pro Val Gln Asn Leu Gly Asp Ser Phe Tyr Cys283528402845Ser Ile Glu Lys Val Phe Leu Cys Thr Gly Ala Asp Gly Tyr Val Pro285028552860Lys Tyr Ser Pro Met Asn Ala Glu Tyr Gly Cys Leu Ala Asp Ser Pro2865287028752880Ser Leu Leu Tyr Arg Phe Lys Ile Val Asp Lys Ala Gln Pro Glu Thr288528902895Gln Ala Thr Ser Phe Gly Asn Val Leu Phe Asn Ala Lys Leu Ala Val290029052910Asp Asp Pro Glu Ala Ile Leu Leu Val Asn Gln Pro Gly Ser Asp Gly291529202925Phe Lys Val Asp Ser Thr Pro Leu Phe Gln Val Ala Leu Gly Arg Glu293029352940Trp Tyr Ile His Thr Ile Tyr Thr Val Arg Ser Lys Asp Asn Ala Asn2945295029552960Arg Gly Ile Gly Lys Arg Ser Val Glu Tyr His Ser Leu Val Ser Gln296529702975Gly Lys Pro Gln Ser Thr Thr Lys Ser Arg Lys Lys Arg Glu Ile Arg298029852990Ser Thr Pro Ser Leu Ala Trp Glu Ile Gly Ala Glu Asn Ser Arg Gly299530003005Thr Asn Ile Gln His Ile Ala Leu Asp Arg Thr Lys Arg Gln Ile Pro301030153020His Gly Arg Ala Pro Pro Asp Gly Ile Leu Pro Trp Glu Leu Asn Ser3025303030353040Pro Ser Ser Ala Val Ser Leu Val Thr Val Val Gly Gly Thr Thr Val304530503055Gly Leu Leu Thr Ile Cys Leu Thr Val Ile Ala Val Leu Met Cys Arg306030653070Gly Lys Glu Ser Phe Arg Gly Lys Asp Ala Pro Lys Gly Ser Ser Ser307530803085Ser Glu Pro Met Val Pro Pro Gln Ser His His Asn Asp Ser Ser Glu309030953100Val3105<210>81<211>457<212>PRT<213>人(Homo sapiens)<400>81Met Gly Cys Ser Gly Ala Trp Gly Leu Ser Cys Pro Cys Pro Gln Thr1 5 10 15Pro Ser Trp Ala Trp Arg Lys Met Arg Thr Pro Ser Met Arg Asn Arg20 25 30Ser Gly Ala Val Trp Ser Arg Ala Ser Val Pro Phe Ser Ala Trp Glu35 40 45Val Glu Val Gln Met Arg Val Thr Gly Leu Gly Arg Arg Gly Ala Gln50 55 60Gly Met Ala Val Trp Tyr Thr Arg Gly Arg Gly His Val Gly Ser Val65 70 75 80Leu Gly Gly Leu Ala Ser Trp Asp Gly Ile Gly Ile Phe Phe Asp Ser85 90 95Pro Ala Glu Asp Thr Gln Asp Ser Pro Ala Ile Arg Val Leu Ala Ser100 105 110Asp Gly His Ile Pro Ser Glu Gln Pro Gly Asp Gly Ala Ser Gln Gly115 120 125Leu Gly Ser Cys His Trp Asp Phe Arg Asn Arg Pro His Pro Phe Arg130 135 140Ala Arg Ile Thr Tyr Trp Gly Gln Arg Leu Arg Met Ser Leu Asn Ser145 150 155 160Gly Leu Thr Pro Ser Asp Pro Gly Glu Phe Cys Val Asp Val Gly Pro165 170 175Leu Leu Leu Val Pro Gly Gly Phe Phe Gly Val Ser Ala Ala Thr Gly180 185 190Thr Leu Ala Asp Asp His Asp Val Leu Ser Phe Leu Thr Phe Ser Leu195 200 205Ser Glu Pro Ser Pro Glu Val Pro Pro Gln Pro Phe Leu Glu Met Gln210 215 220His Val Arg Leu Ala Arg Gln Leu Glu Gly Leu Trp Ala Arg Leu Gly225 230 235 240Leu Gly Thr Arg Glu Asp Val Thr Pro Lys Ser Asp Ser Glu Ala Gln245 250 255Gly Glu Gly Glu Arg Leu Phe Asp Leu Glu Glu Thr Leu Gly Arg His260 265 270Arg Arg Ile Leu Gln Ala Leu Arg Gly Leu Ser Lys Gln Leu Ala Gln275 280 285Ala Glu Arg Gln Trp Lys Lys Gln Leu Gly Pro Gln Ala Lys Pro Gly290 295 300Leu Thr Glu Ala Gly Asp Ala Ala Val Arg Met Ala Ala Glu Ala Gln305 310 315 320Val Ser Tyr Leu Pro Val Gly Ile Glu His His Phe Leu Glu Leu Asp325 330 335His Ile Leu Gly Leu Leu Gln Glu Glu Leu Arg Gly Pro Ala Lys Ala340 345 350Ala Ala Lys Ala Pro Arg Pro Pro Gly Gln Pro Pro Arg Ala Ser Ser355 360 365Cys Leu Gln Pro Gly Ile Phe Leu Phe Tyr Leu Leu Ile Gln Thr Val370 375 380Gly Phe Phe Gly Tyr Val His Phe Arg Arg Pro Val Pro Arg Pro Ala385 390 395 400Lys Thr Met Ala Phe Met Val Lys Thr Met Val Gly Gly Gln Leu Lys405 410 415Asn Leu Thr Gly Ser Leu Gly Gly Gly Glu Asp Lys Gly Asp Gly Asp420 425 430Lys Ser Ala Ala Glu Ala Gln Gly Met Ser Arg Glu Glu Tyr Glu Glu435 440 445Tyr Gln Lys Gln Leu Val Glu Glu Lys450 455<210>82<211>526<212>PRT<213>人(Homo sapiens)<400>82Met Pro Ala Val Ser Gly Pro Gly Pro Leu Phe Cys Leu Leu Leu Leu1 5 10 15Leu Leu Asp Pro His Ser Pro Glu Thr Gly Cys Pro Pro Leu Arg Arg20 25 30Phe Glu Tyr Lys Leu Ser Phe Lys Gly Pro Arg Leu Ala Leu Pro Gly35 40 45Ala Gly Ile Pro Phe Trp Ser His His Gly Asp Ala Ile Leu Gly Leu50 55 60Glu Glu Val Arg Leu Thr Pro Ser Met Arg Asn Arg Ser Gly Ala Val65 70 75 80Trp Ser Arg Ala Ser Val Pro Phe Ser Ala Trp Glu Val Glu Val Gln85 90 95Met Arg Val Thr Gly Leu Gly Arg Arg Gly Ala Gln Gly Met Ala Val100 105 110Trp Tyr Thr Arg Gly Arg Gly His Val Gly Ser Val Leu Gly Gly Leu115 120 125Ala Ser Trp Asp Gly Ile Gly Ile Phe Phe Asp Ser Pro Ala Glu Asp130 135 140Thr Gln Asp Ser Pro Ala Ile Arg Val Leu Ala Ser Asp Gly His Ile145 150 155 160Pro Ser Glu Gln Pro Gly Asp Gly Ala Ser Gln Gly Leu Gly Ser Cys165 170 175His Trp Asp Phe Arg Asn Arg Pro His Pro Phe Arg Ala Arg Ile Thr180 185 190Tyr Trp Gly Gln Arg Leu Arg Met Ser Leu Asn Ser Gly Leu Thr Pro195 200 205Ser Asp Pro Gly Glu Phe Cys Val Asp Val Gly Pro Leu Leu Leu Val210 215 220Pro Gly Gly Phe Phe Gly Val Ser Ala Ala Thr Gly Thr Leu Ala Asp225 230 235 240Asp His Asp Val Leu Ser Phe Leu Thr Phe Ser Leu Ser Glu Pro Ser245 250 255Pro Glu Val Pro Pro Gln Pro Phe Leu Glu Met Gln His Val Arg Leu260 265 270Ala Arg Gln Leu Glu Gly Leu Trp Ala Arg Leu Gly Leu Gly Thr Arg275 280 285Glu Asp Val Thr Pro Lys Ser Asp Ser Glu Ala Gln Gly Glu Gly Glu290 295 300Arg Leu Phe Asp Leu Glu Glu Thr Leu Gly Arg His Arg Arg Ile Leu305 310 315 320Gln Ala Leu Arg Gly Leu Ser Lys Gln Leu Ala Gln Ala Glu Arg Gln325 330 335Trp Lys Lys Gln Leu Gly Pro Pro Gly Gln Ala Arg Pro Asp Gly Gly340 345 350Trp Ala Leu Asp Ala Ser Cys Gln Ile Pro Ser Thr Pro Gly Arg Gly355 360 365Gly His Leu Ser Met Ser Leu Asn Lys Asp Ser Ala Lys Val Gly Ala370 375 380Leu Leu His Gly Gln Trp Thr Leu Leu Gln Ala Leu Gln Glu Met Arg385 390 395 400Asp Ala Ala Val Arg Met Ala Ala Glu Ala Gln Val Ser Tyr Leu Pro405 410 415Val Gly Ile Glu His His Phe Leu Glu Leu Asp His Ile Leu Gly Leu420 425 430Leu Gln Glu Glu Leu Arg Gly Pro Ala Lys Ala Ala Ala Lys Ala Pro435 440 445Arg Pro Pro Gly Gln Pro Pro Arg Ala Ser Ser Cys Leu Gln Pro Gly450 455 460Ile Phe Leu Phe Tyr Leu Leu Ile Gln Thr Val Gly Phe Phe Gly Tyr465 470 475 480Val His Phe Arg Gln Glu Leu Asn Lys Ser Leu Gln Glu Cys Leu Ser485 490 495Thr Gly Ser Leu Pro Leu Gly Pro Ala Pro His Thr Pro Arg Ala Leu500 505 510Gly Ile Leu Arg Arg Gln Pro Leu Pro Ala Ser Met Pro Ala515 520 525<210>83<211>904<212>PRT<213>人(Homo sapiens)<400>83Met Leu Leu Ala Leu Cys Ser Ser Leu Ala Leu Ile Phe Ala Ala Pro1 5 10 15Val Ser Gly Gln Leu Glu His Ser Gly Asn Tyr Tyr Cys Thr Ala Asp20 25 30Asn Gly Phe Gly Pro Gln His Ser Glu Val Val Ser Leu Ser Val Thr35 40 45Val Pro Val Ser His Pro Val Leu Thr Leu Ser Ser Ala Glu Ala Leu50 55 60Thr Phe Glu Gly Ala Thr Val Thr Leu His Ser Ser Leu Ile Leu Gln65 70 75 80Ala Pro Leu Ser Val Phe Glu Gly Asp Phe Val Val Leu Arg Cys Arg85 90 95Ala Lys Ala Glu Val Thr Leu Asn Thr Met Tyr Lys Asn Gly Asn Val100 105 110Leu Thr Phe Leu Asn Lys Ser Ser Asp Phe His Ile His His Ala Ser115 120 125Leu Lys Asp Asn Gly Ala Tyr His Phe Thr Gly Phe Asn Gly Ser Asn130 135 140Phe Ser Val Ser Ser Asn Ile Val Lys Ile Gln Val Gln Glu His Leu145 150 155 160Leu Pro Gln Trp Phe Leu Lys Ala Pro Asp Pro Thr Val Ala Leu Ser165 170 175Glu Ile Phe Ser Val Asn Arg Gly Pro Leu Leu Thr Gly Thr Gly Ser180 185 190Arg Val Met Thr Pro Trp Ile Tyr Phe Pro Thr Glu Asp Trp Asn Phe195 200 205Thr Leu Ile Pro Ile Thr Val Asp Asp Ala Cys Lys Arg Pro Cys Ala210 215 220Pro Arg Ala Pro Trp Glu Val Gly Ser Leu Thr Pro Gly Lys Ser Phe225 230 235 240Gln Gln Lys Gly Asn Pro Asp Leu Leu Met Gly Pro Phe Asp Val Leu245 250 255His Leu Ser Leu Ile Thr Leu Phe Cys Asn Met Ala Gly Ser Leu Phe260 265 270Tyr Tyr Met Glu Leu Gly Glu Lys Lys Asp Ala Leu Phe Val Thr Gly275 280 285Asn Glu Ser Arg Ser Tyr His Trp Phe Gln Lys Phe Ser Leu Ala Gly290 295 300Gly Gln Glu Ala Asp Gln Lys Leu Trp Phe Pro Pro Gly Leu Met Ser305 310 315 320Gln Asp Ile Phe Ile Tyr Ile Arg Gln Gly Glu Ser Cys Leu Val Ile325 330 335Glu Met Phe His Gln Val Tyr Arg Arg Pro Ala Gly Gly Val Pro Val340 345 350Glu His Met Ser Val Trp Ala Leu Arg Val Asn Ser Ser Gly Leu Phe355 360 365Ala Tyr Ala Asp Gly Trp Leu Phe Thr Leu Phe Gln Leu Gln Ser Val370 375 380Asp Asn Leu Ser Pro Ser Thr Gln Ser Gln Thr His Glu Gly His Glu385 390 395 400Lys Leu Cys Pro Phe Leu Ala Ile Gly Pro Pro Ala His Ser Arg Gly405 410 415Ser Phe Leu Arg Ala Lys Lys Ser Leu Val Ala Tyr Ile Lys Gly Asn420 425 430Gln Leu Ser Phe Pro Pro Val Glu Asp Leu Leu Pro Lys Ser Gln Trp435 440 445Pro Cys Ile Gln Val Leu Pro Arg Asn Ile Ala Ala Ala Ala His Lys450 455 460Pro Val Ile Ser Val His Pro Pro Trp Thr Thr Phe Phe Lys Gly Glu465 470 475 480Arg Val Thr Leu Thr Cys Asn Gly Phe Gln Phe Tyr Ala Thr Glu Lys485 490 495Thr Thr Trp Tyr His Arg His Tyr Trp Gly Glu Lys Leu Thr Leu Thr500 505 510Pro Gly Asn Thr Leu Glu Val Arg Glu Ser Gly Leu Tyr Arg Cys Gln515 520 525Ala Arg Gly Ser Pro Arg Ser Asn Pro Val Arg Leu Leu Phe Ser Ser530 535 540Gly Glu Lys Glu Asp Cys Val Ser Asp Lys Asn Pro Ala Thr Asn His545 550 555 560Thr Pro Met Ser Arg Lys Arg Ser Ser Cys Ser Ser Leu Ser Ala Thr565 570 575Ser Phe Ile Ala Pro Ala Leu Arg Leu Asp Ser Leu Ile Leu Gln Ala580 585 590Pro Tyr Ser Val Phe Glu Gly Asp Thr Leu Val Leu Arg Cys His Arg595 600 605Arg Arg Lys Glu Lys Leu Thr Ala Val Lys Tyr Thr Trp Asn Gly Asn610 615 620Ile Leu Ser Ile Ser Asn Lys Ser Trp Asp Leu Leu Ile Pro Gln Ala625 630 635 640Ser Ser Asn Asn Asn Gly Asn Tyr Arg Cys Ile Gly Tyr Gly Asp Glu645 650 655Asn Asp Val Phe Arg Ser Asn Phe Lys Ile Ile Lys Ile Gln Gly Ile660 665 670Pro Val Ser Gly Val Leu Leu Glu Thr Gln Pro Ser Gly Gly Gln Ala675 680 685Val Glu Gly Glu Met Leu Val Leu Val Cys Ser Val Ala Glu Gly Thr690 695 700Gly Asp Thr Thr Phe Ser Trp His Arg Glu Asp Met Gln Glu Ser Leu705 710 715 720Gly Arg Lys Thr Gln Arg Ser Leu Arg Ala Glu Leu Glu Leu Pro Ala725 730 735Ile Arg Gln Ser His Ala Gly Gly Tyr Tyr Cys Thr Ala Asp Asn Ser740 745 750Tyr Gly Pro Val Gln Ser Met Val Leu Asn Val Thr Val Arg Glu Thr755 760 765Pro Gly Asn Arg Asp Gly Leu Val Ala Ala Gly Ala Thr Gly Gly Leu770 775 780Leu Ser Ala Leu Leu Leu Ala Val Ala Leu Leu Phe His Cys Trp Arg785 790 795 800Arg Arg Lys Ser Val His Pro Lys Lys Gly Asp Leu Val Tyr Ser Glu805 810 815Ile Gln Thr Thr Gln Leu Gly Glu Glu Glu Glu Gly Asn His Gly Asn820 825 830Lys Asn Gln Glu Leu Glu Leu Val Asn Val Gly Glu Ser Phe Ser His835 840 845Arg Ala Cys Ile Trp Ser Thr Leu Met Gly Thr Cys Gln Thr Ile Gly850 855 860Gly Ala Asn Thr Ser Arg Thr Leu Leu Glu Asp Lys Asp Val Ser Val865 870 875 880Val Tyr Ser Glu Val Lys Thr Gln His Pro Asp Asn Ser Ala Gly Lys885 890 895Ile Ser Ser Lys Asp Glu Glu Ser900<210>84<211>515<212>PRT<213>人(Homo sapiens)<400>84Met Leu Leu Trp Ala Ser Leu Leu Ala Phe Ala Pro Val Cys Gly Gln1 5 10 15Ser Ala Ala Ala His Lys Pro Val Ile Ser Val His Pro Pro Trp Thr20 25 30Thr Phe Phe Lys Gly Glu Arg Val Thr Leu Thr Cys Asn Gly Phe Gln35 40 45Phe Tyr Ala Thr Glu Lys Thr Thr Trp Tyr His Arg His Tyr Trp Gly50 55 60Glu Lys Leu Thr Leu Thr Pro Gly Asn Thr Leu Glu Val Arg Glu Ser65 70 75 80Gly Leu Tyr Arg Cys Gln Ala Arg Gly Ser Pro Arg Ser Asn Pro Val85 90 95Arg Leu Leu Phe Ser Ser Asp Ser Leu Ile Leu Gln Ala Pro Tyr Ser100 105 110Val Phe Glu Gly Asp Thr Leu Val Leu Arg Cys His Arg Arg Arg Lys115 120 125Glu Lys Leu Thr Ala Val Lys Tyr Thr Trp Asn Gly Asn Ile Leu Ser130 135 140Ile Ser Asn Lys Ser Trp Asp Leu Leu Ile Pro Gln Ala Ser Ser Asn145 150 155 160Asn Asn Gly Asn Tyr Arg Cys Ile Gly Tyr Gly Asp Glu Asn Asp Val165 170 175Phe Arg Ser Asn Phe Lys Ile Ile Lys Ile Gln Glu Leu Phe Pro His180 185 190Pro Glu Leu Lys Ala Thr Asp Ser Gln Pro Thr Glu Gly Asn Ser Val195 200 205Asn Leu Ser Cys Glu Thr Gln Leu Pro Pro Glu Arg Ser Asp Thr Pro210 215 220Leu His Phe Asn Phe Phe Arg Asp Gly Glu Val Ile Leu Ser Asp Trp225 230 235 240Ser Thr Tyr Pro Glu Leu Gln Leu Pro Thr Val Trp Arg Glu Asn Ser245 250 255Gly Ser Tyr Trp Cys Gly Ala Glu Thr Val Arg Gly Asn Ile His Lys260 265 270His Ser Pro Ser Leu Gln Ile His Val Gln Arg Ile Pro Val Ser Gly275 280 285Val Leu Leu Glu Thr Gln Pro Ser Gly Gly Gln Ala Val Glu Gly Glu290 295 300Met Leu Val Leu Val Cys Ser Val Ala Glu Gly Thr Gly Asp Thr Thr305 310 315 320Phe Ser Trp His Arg Glu Asp Met Gln Glu Ser Leu Gly Arg Lys Thr325 330 335Gln Arg Ser Leu Arg Ala Glu Leu Glu Leu Pro Ala Ile Arg Gln Ser340 345 350His Ala Gly Gly Tyr Tyr Cys Thr Ala Asp Asn Ser Tyr Gly Pro Val355 360 365Gln Ser Met Val Leu Asn Val Thr Val Arg Glu Thr Pro Gly Asn Arg370 375 380Asp Gly Leu Val Ala Ala Gly Ala Thr Gly Gly Leu Leu Ser Ala Leu385 390 395 400Leu Leu Ala Val Ala Leu Leu Phe His Cys Trp Arg Arg Arg Lys Ser405 410 415Gly Val Gly Phe Leu Gly Asp Glu Thr Arg Leu Pro Pro Ala Pro Gly420 425 430Pro Gly Glu Ser Ser His Ser Ile Cys Pro Ala Gln Val Glu Leu Gln435 440 445Ser Leu Tyr Val Asp Val His Pro Lys Lys Gly Asp Leu Val Tyr Ser450 455 460Glu Ile Gln Thr Thr Gln Leu Gly Glu Glu Glu Glu Ala Asn Thr Ser465 470 475 480Arg Thr Leu Leu Glu Asp Lys Asp Val Ser Val Val Tyr Ser Glu Val485 490 495Lys Thr Gln His Pro Asp Asn Ser Ala Gly Lys Ile Ser Ser Lys Asp500 505 510Glu Glu Ser515<210>85<211>831<212>PRT<213>人(Homo sapiens)<400>85Asx Met Ala Val Gly Gly Gly His Lys Gly Val Arg Cys Pro Pro Ser1 5 10 15Ala Arg Ser Ser Gln Val Pro Thr Cys Cys Ala Gly Trp Arg Gln Gln20 25 30Gly Asp Glu Cys Gly Ile Ala Val Cys Glu Gly Asn Ser Thr Cys Ser35 40 45Glu Asn Glu Val Cys Val Arg Pro Gly Glu Cys Arg Cys Arg Hi s Gly50 55 60Tyr Phe Gly Ala Asn Cys Asp Thr Lys Cys Pro Arg Gln Phe Trp Gly65 70 75 80Pro Asp Cys Lys Glu Leu Cys Ser Cys His Pro His Gly Gln Cys Glu85 90 95Asp Val Thr Gly Gln Cys Thr Cys His Ala Arg Arg Trp Gly Ala Arg100 105 110Cys Glu His Ala Cys Gln Cys Gln His Gly Thr Cys His Pro Arg Ser115 120 125Gly Ala Cys Arg Cys Glu Ser Gly Trp Trp Gly Ala Gln Cys Ala Ser130 135 140Ala Cys Tyr Cys Ser Ala Thr Ser Arg Cys Asp Pro Gln Thr Gly Ala145 150 155 160Cys Leu Cys His Ala Gly Trp Trp Gly Arg Ser Cys Asn Asn Gln Cys165 170 175Ala Cys Asn Ser Ser Pro Cys Glu Gln Gln Ser Gly Arg Cys Gln Cys180 185 190Arg Glu Arg Thr Phe Gly Ala Arg Cys Asp Arg Tyr Cys Gln Cys Phe195 200 205Arg Gly Arg Cys His Pro Val Asp Gly Thr Cys Ala Cys Glu Pro Gly210 215 220Tyr Arg Gly Lys Tyr Cys Arg Glu Pro Cys Pro Ala Gly Phe Tyr Gly225 230 235 240Leu Gly Cys Arg Arg Arg Cys Gly Gln Cys Lys Gly Gln Gln Pro Cys245 250 255Thr Val Ala Glu Gly Arg Cys Leu Thr Cys Glu Pro Gly Trp Asn Gly260 265 270Thr Lys Cys Asp Gln Pro Cys Ala Thr Gly Phe Tyr Gly Glu Gly Cys275 280 285Ser His Arg Cys Pro Pro Cys Arg Asp Gly His Ala Cys Asn His Val290 295 300Thr Gly Lys Cys Thr Arg Cys Asn Ala Gly Trp Ile Gly Asp Arg Cys305 310 315 320Glu Thr Lys Cys Ser Asn Gly Thr Tyr Gly Glu Asp Cys Ala Phe Val325 330 335Cys Ala Asp Cys Gly Ser Gly His Cys Asp Phe Gln Ser Gly Arg Cys340 345 350Leu Cys Ser Pro Gly Val His Gly Pro His Cys Asn Val Thr Cys Pro355 360 365Pro Gly Leu His Gly Ala Asp Cys Ala Gln Ala Cys Ser Cys His Glu370 375 380Asp Thr Cys Asp Pro Val Thr Gly Ala Cys His Leu Glu Thr Asn Gln385 390 395 400Arg Lys Gly Val Met Gly Ala Gly Ala Leu Leu Val Leu Leu Val Cys405 410 415Leu Leu Leu Ser Leu Leu Gly Cys Cys Cys Ala Cys Arg Gly Lys Asp420 425 430Pro Thr Arg Arg Pro Arg Pro Arg Arg Glu Leu Ser Leu Gly Arg Lys435 440 445Lys Ala Pro His Arg Leu Cys Gly Arg Phe Ser Arg Ile Ser Met Lys450 455 460Leu Pro Arg Ile Pro Leu Arg Arg Gln Lys Leu Pro Lys Val Val Val465 470 475 480Ala His His Asp Leu Asp Asn Thr Leu Asn Cys Ser Phe Leu Glu Pro485 490 495Pro Ser Gly Leu Glu Gln Pro Ser Pro Ser Trp Ser Ser Arg Ala Ser500 505 510Phe Ser Ser Phe Asp Thr Thr Asp Glu Gly Pro Val Tyr Cys Val Pro515 520 525His Glu Glu Ala Pro Ala Glu Ser Arg Asp Pro Glu Val Pro Thr Val530 535 540Pro Ala Glu Ala Pro Ala Pro Ser Pro Val Pro Leu Thr Thr Pro Ala545 550 555 560Ser Ala Glu Glu Ala Ile Pro Leu Pro Ala Ser Ser Asp Ser Glu Arg565 570 575Ser Ala Ser Ser Val Glu Gly Pro Gly Gly Ala Leu Tyr Ala Arg Val580 585 590Ala Arg Arg Glu Ala Arg Pro Ala Arg Ala Arg Gly Glu Ile Gly Gly595 600 605Leu Ser Leu Ser Pro Ser Pro Glu Arg Arg Lys Pro Pro Pro Pro Asp610 615 620Pro Ala Thr Lys Pro Lys Val Ser Trp Ile His Gly Lys His Ser Ala625 630 635 640Ala Ala Ala Gly Arg Ala Pro Ser Pro Pro Pro Pro Gly Ser Glu Ala645 650 655Ala Pro Ser Pro Ser Lys Arg Lys Arg Thr Pro Ser Asp Lys Ser Ala660 665 670His Thr Val Glu His Gly Ser Pro Arg Thr Arg Asp Pro Thr Pro Arg675 680 685Pro Pro Gly Leu Pro Glu Glu Ala Thr Ala Leu Ala Ala Pro Ser Pro690 695 700Pro Arg Ala Arg Ala Arg Ala Ala Pro Arg Pro Leu Gly Ala His Gly705 710 715 720Arg Arg Arg Ser Pro Ala Lys Arg Ala Glu Ala Ala Ser Met Leu Ala725 730 735Ala Asp Val Arg Gly Lys Thr Arg Ser Leu Gly Arg Ala Glu Val Ala740 745 750Leu Gly Ala Gln Gly Pro Arg Glu Lys Pro Ala Pro Pro Gln Lys Ala755 760 765Lys Arg Ser Val Pro Pro Ala Ser Pro Ala Arg Ala Pro Pro Ala Thr770 775 780Glu Thr Pro Gly Pro Glu Lys Ala Ala Thr Asp Leu Pro Ala Pro Glu785 790 795 800Thr Pro Arg Lys Lys Thr Pro Ile Gln Lys Pro Pro Arg Lys Lys Ser805 810 815Arg Glu Ala Ala Gly Glu Leu Gly Arg Ala Gly Ala Pro Thr Leu820 825 830<210>86<211>871<212>PRT<213>人(Homo sapiens)<400>86Asx Met Glu Gly Ala Gly Pro Arg Gly Ala Gly Pro Ala Arg Arg Arg1 5 10 15Gly Ala Gly Gly Pro Pro Ser Pro Leu Leu Pro Ser Leu Leu Leu Leu20 25 30Leu Leu Leu Trp Met Leu Pro Asp Thr Val Ala Pro Gln Glu Leu Asn35 40 45Pro Arg Gly Arg Asn Val Cys Arg Ala Pro Gly Ser Gln Val Pro Thr50 55 60Cys Cys Ala Gly Trp Arg Gln Gln Gly Asp Glu Cys Gly Ile Ala Val65 70 75 80Cys Glu Gly Asn Ser Thr Cys Ser Glu Asn Glu Val Cys Val Arg Pro85 90 95Gly Glu Cys Arg Cys Arg His Gly Tyr Phe Gly Ala Asn Cys Asp Thr100 105 110Lys Cys Pro Arg Gln Phe Trp Gly Pro Asp Cys Lys Glu Leu Cys Ser115 120 125Cys His Pro His Gly Gln Cys Glu Asp Val Thr Gly Gln Cys Thr Cys130 135 140His Ala Arg Arg Trp Gly Ala Arg Cys Glu His Ala Cys Gln Cys Gln145 150 155 160His Gly Thr Cys His Pro Arg Ser Gly Ala Cys Arg Cys Glu Ser Gly165 170 175Trp Trp Gly Ala Gln Cys Ala Ser Ala Cys Tyr Cys Ser Ala Thr Ser180 185 190Arg Cys Asp Pro Gln Thr Gly Ala Cys Leu Cys His Ala Gly Trp Trp195 200 205Gly Arg Ser Cys Asn Asn Gln Cys Ala Cys Asn Ser Ser Pro Cys Glu210 215 220Gln Gln Ser Gly Arg Cys Gln Cys Arg Glu Arg Thr Phe Gly Ala Arg225 230 235 240Cys Asp Arg Tyr Cys Gln Cys Phe Arg Gly Arg Cys His Pro Val Asp245 250 255Gly Thr Cys Ala Cys Glu Pro Gly Tyr Arg Gly Lys Tyr Cys Arg Glu260 265 270Pro Cys Pro Ala Gly Phe Tyr Gly Leu Gly Cys Arg Arg Arg Cys Gly275 280 285Gln Cys Lys Gly Gln Gln Pro Cys Thr Val Ala Glu Gly Arg Cys Leu290 295 300Thr Cys Glu Pro Gly Trp Asn Gly Thr Lys Cys Asp Gln Pro Cys Ala305 310 315 320Thr Gly Phe Tyr Gly Glu Gly Cys Ser His Arg Cys Pro Pro Cys Arg325 330 335Asp Gly His Ala Cys Asn His Val Thr Gly Lys Cys Thr Arg Cys Asn340 345 350Ala Gly Trp Ile Gly Asp Arg Cys Glu Thr Lys Cys Ser Asn Gly Thr355 360 365Tyr Gly Glu Asp Cys Ala Phe Val Cys Ala Asp Cys Gly Ser Gly His370 375 380Cys Asp Phe Gln Ser Gly Arg Cys Leu Cys Ser Pro Gly Val His Gly385 390 395 400Pro His Cys Asn Val Thr Cys Pro Pro Gly Leu His Gly Ala Asp Cys405 410 415Ala Gln Ala Cys Ser Cys His Glu Asp Thr Cys Asp Pro Val Thr Gly420 425 430Ala Cys His Leu Glu Thr Asn Gln Arg Lys Gly Val Met Gly Ala Gly435 440 445Ala Leu Leu Val Leu Leu Val Cys Leu Leu Leu Ser Leu Leu Gly Cys450 455 460Cys Cys Ala Cys Arg Gly Lys Asp Pro Thr Arg Arg Pro Arg Pro Arg465 470 475 480Arg Glu Leu Ser Leu Gly Arg Lys Lys Ala Pro His Arg Leu Cys Gly485 490 495Arg Phe Ser Arg Ile Ser Met Lys Leu Pro Arg Ile Pro Leu Arg Arg500 505 510Gln Lys Leu Pro Lys Val Val Val Ala His His Asp Leu Asp Asn Thr515 520 525Leu Asn Cys Ser Phe Leu Glu Pro Pro Ser Gly Leu Glu Gln Pro Ser530 535 540Pro Ser Trp Ser Ser Arg Ala Ser Phe Ser Ser Phe Asp Thr Thr Asp545 550 555 560Glu Gly Pro Val Tyr Cys Val Pro His Glu Glu Ala Pro Ala Glu Ser565 570 575Arg Asp Pro Glu Val Pro Thr Val Pro Ala Glu Ala Pro Ala Pro Ser580 585 590Pro Val Pro Leu Thr Thr Pro Ala Ser Ala Glu Glu Ala Ile Pro Leu595 600 605Pro Ala Ser Ser Asp Ser Glu Arg Ser Ala Ser Ser Val Glu Gly Pro610 615 620Gly Gly Ala Leu Tyr Ala Arg Val Ala Arg Arg Glu Ala Arg Pro Ala625 630 635 640Arg Ala Arg Gly Glu Ile Gly Gly Leu Ser Leu Ser Pro Ser Pro Glu645 650 655Arg Arg Lys Pro Pro Pro Pro Asp Pro Ala Thr Lys Pro Lys Val Ser660 665 670Trp Ile His Gly Lys His Ser Ala Ala Ala Ala Gly Arg Ala Pro Ser675 680 685Pro Pro Pro Pro Gly Ser Glu Ala Ala Pro Ser Pro Ser Lys Arg Lys690 695 700Arg Thr Pro Ser Asp Lys Ser Ala His Thr Val Glu His Gly Ser Pro705 710 715 720Arg Thr Arg Asp Pro Thr Pro Arg Pro Pro Gly Leu Pro Glu Glu Ala725 730 735Thr Ala Leu Ala Ala Pro Ser Pro Pro Arg Ala Arg Ala Arg Ala Ala740 745 750Pro Arg Pro Leu Gly Ala His Gly Arg Arg Arg Ser Pro Ala Lys Arg755 760 765Ala Glu Ala Ala Ser Met Leu Ala Ala Asp Val Arg Gly Lys Thr Arg770 775 780Ser Leu Gly Arg Ala Glu Val Ala Leu Gly Ala Gln Gly Pro Arg Glu785 790 795 800Lys Pro Ala Pro Pro Gln Lys Ala Lys Arg Ser Val Pro Pro Ala Ser805 810 815Pro Ala Arg Ala Pro Pro Ala Thr Glu Thr Pro Gly Pro Glu Lys Ala820 825 830Ala Thr Asp Leu Pro Ala Pro Glu Thr Pro Arg Lys Lys Thr Pro Ile835 840 845Gln Lys Pro Pro Arg Lys Lys Ser Arg Glu Ala Ala Gly Glu Leu Gly850 855 860Arg Ala Gly Ala Pro Thr Leu865 870<210>87<211>134<212>PRT<213>人(Homo sapiens)<400>87Ile Asp Cys Arg Ala Glu Gln Gly Arg Thr Pro Leu Met Val Ala Val1 5 10 15Gly Leu Pro Asp Pro Ala Leu Arg Ala Arg Phe Val Arg Leu Leu Leu20 25 30Glu Gln Gly Ala Ala Val Asn Leu Arg Asp Glu Arg Gly Arg Thr Ala35 40 45Leu Ser Leu Ala Cys Glu Arg Gly His Leu Asp Ala Val Gln Leu Leu50 55 60Val Gln Phe Ser Gly Asp Pro Glu Ala Ala Asp Ser Ala Gly Asn Ser65 70 75 80Pro Val Met Trp Ala Ala Ala Cys Gly His Gly Ala Val Leu Glu Phe85 90 95Leu Val Arg Ser Phe Arg Arg Leu Gly Leu Arg Leu Asp Arg Thr Asn100 105 110Arg Ala Gly Leu Thr Ala Leu Gln Leu Ala Ala Ala Arg Gly His Gly115 120 125Thr Cys Val Gln Ala Leu130<210>88<211>324<212>PRT<213>人(Homo sapiens)<400>88Met Leu Lys Pro Lys Asp Leu Cys Pro Arg Ala Gly Thr Arg Thr Phe1 5 10 15Leu Glu Ala Met Gln Ala Gly Lys Val His Leu Ala Arg Phe Val Leu20 25 30Asp Ala Leu Asp Arg Ser Ile Ile Asp Cys Arg Ala Glu Gln Gly Arg35 40 45Thr Pro Leu Met Val Ala Val Gly Leu Pro Asp Pro Ala Leu Arg Ala50 55 60Arg Phe Val Arg Leu Leu Leu Glu Gln Gly Ala Ala Val Asn Leu Arg65 70 75 80Asp Glu Arg Gly Arg Thr Ala Leu Ser Leu Ala Cys Glu Arg Gly His85 90 95Leu Asp Ala Val Gln Leu Leu Val Gln Phe Ser Gly Asp Pro Glu Ala100 105 110Ala Asp Ser Ala Gly Asn Ser Pro Val Met Trp Ala Ala Ala Cys Gly115 120 125His Gly Ala Val Leu Glu Phe Leu Val Arg Ser Phe Arg Arg Leu Gly130 135 140Leu Arg Leu Asp Arg Thr Asn Arg Ala Gly Leu Thr Ala Leu Gln Leu145 150 155 160Ala Ala Ala Arg Gly His Gly Thr Ser Ala Gly Gly His Gly Gly Glu165 170 175Ala Gly Ser Ala Gly Lys Asn Ser Gly Arg His Arg Ala Gln Gly Ser180 185 190Glu Arg Pro Glu Leu Gly Arg Ser Met Ser Leu Ala Leu Gly Ala Val195 200 205Thr Glu Glu Glu Ala Ala Arg Leu Arg Ala Gly Ala Leu Met Ala Leu210 215 220Pro Asn Ser Pro Gln Ser Ser Gly Thr Gly Arg Trp Arg Ser Gln Glu225 230 235 240Val Leu Glu Gly Ala Pro Pro Thr Leu Ala Gln Ala Pro Ile Gly Leu245 250 255Ser Pro His Pro Glu Gly Gly Pro Gly Ser Gly Arg Leu Gly Leu Arg260 265 270Arg Arg Ser Thr Ala Pro Asp Ile Pro Ser Leu Val Gly Glu Ala Pro275 280 285Gly Pro Glu Ser Gly Pro Glu Leu Glu Ala Asn Ala Leu Ser Val Ser290 295 300Val Pro Gly Pro Asn Pro Trp Gln Ala Gly Thr Glu Ala Val Val Leu305 310 315 320Arg Ala Gln Arg
权利要求
1.一种分离的多肽,该多肽选自(a)一种分离的多肽,由包含表I所列的一种序列的多核苷酸编码;(b)一种分离的多肽,包含表I所列的一种多肽序列;和(c)表I所列的一种基因的多肽序列。
2.一种分离的多核苷酸,该多核苷酸选自(a)一种分离的多核苷酸,其包含表I所列的一种多核苷酸序列;(b)表I所列的一种基因的分离的多核苷酸;(c)一种分离的多核苷酸,其包含编码表I所列的一种多肽的多核苷酸序列;(d)一种分离的多核苷酸,编码表I所列的一种多肽;(e)一种多核苷酸,该多核苷酸是(a)到(d)的多核苷酸的RNA等价物;或者与上述分离的多核苷酸互补的多核苷酸序列。
3.一种表达载体,其包含多核苷酸,当所述表达载体出现在相容性宿主细胞中时,该多核苷酸能够产生权利要求1的多肽。
4.一种制备重组宿主细胞的方法,其中包括下述步骤将包含能产生权利要求1中所述多肽的多核苷酸的表达载体导入细胞,从而使得所述宿主细胞在合适的培养条件下产生所述的多肽。
5.一种用权利要求4所述方法制备而成的重组宿主细胞。
6.一种膜,其为表达所述多肽的权利要求5所述重组宿主细胞的膜。
7.一种制备多肽的方法,其中包括将权利要求5中所述宿主细胞培养在足以制备出所述多肽的条件下,然后从所述培养中回收所述多肽。
全文摘要
本发明公开了表I中所列基因的多肽和多核苷酸,以及用重组技术制备所述多肽的方法。本发明还公开了在诊断试验中利用表I所列基因的多肽和多核苷酸的方法。
文档编号A61K38/00GK1474869SQ01818830
公开日2004年2月11日 申请日期2001年9月13日 优先权日2000年9月13日
发明者潘卡杰·阿加沃尔, 约翰·P·戈格斯韦尔, 赖英塔, 谢尔比·A·马滕森, 兰德尔·F·史密斯, 杰伊·C·斯特鲁姆, 谢青, A 马滕森, F 史密斯, C 斯特鲁姆, P 戈格斯韦尔, 潘卡杰 阿加沃尔 申请人:史密丝克莱恩比彻姆公司, 史密丝克莱比奇曼公司, 葛兰素集团有限公司