新型化合物的制作方法

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该多肽的多核苷酸，本发明还涉及它们在诊断中的应用，以及它们在鉴定有潜在治疗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相连(下文往往统称为分泌蛋白或分泌多肽)。
背景技术：
由于“功能基因组”，即以基因组或基因为基础的高流通量(highthroughput)生物学的出现，使得药物开发方法现正经历一场重大变革。以鉴定基因或基因产物作治疗靶标为手段的方法迅速取代了原来以“定位克隆”为基础的方法。一种表型，即一种生物功能或遗传疾病被鉴定出来后，接着就根据其遗传图谱位置回溯到负责基因(responsible gene)。
功能基因组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，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。需要不断对其他基因及其有关的蛋白/多肽进行鉴定和定性以作为药物开发的靶标。
那些天然分泌到血液、淋巴或其他体液中，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。原因在于该目标可以相对容易地将治疗蛋白靶向其作用位置(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，即蛇毒液中的毒素侵入细胞的机制外)。因此，将蛋白治疗物靶入细胞就面临着巨大困难。
分泌型及膜结合蛋白(membrane-associated protein)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、过氧化物歧化酶、剪接体蛋白、7TM(跨膜蛋白)蛋白也称为G-蛋白偶联受体、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蛋白、消化酶)、脱氧核糖核酸酶I、等。
FDA或外国机构承认治疗作用的分泌型或膜结合蛋白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 by Genentech)、hyaulorindase(Wydase by Wyeth-Ayerst)，α链球菌脱氧核糖核酸酶(Pulmozyme\by Genentech)，Chymodiactin(chymopapain by Knoll)，糖脑苷酶(Ceredase by Genzyme)，链激酶(Kabikinase by Pharmacia)(Streptase by Astra)等。这表明分泌型及膜结合蛋白质作为治疗靶标已有确证的历史。显然，需要对其他能够预防、减缓或纠正功能紊乱或疾病的分泌型及膜结合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、结肠癌及其他恶性肿瘤、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、精神发育或性发育障碍、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中列出的特定多肽及基因的多核苷酸，包括制备其的重组材料和方法。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、功能或代谢异常而引发的疾病、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与每个所附序列公开的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。
发明描述第一方面，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序列的多核苷酸编码的分离多肽，本发明中提到序列表中所列多核苷酸或多肽时，要参考序列表部分的序列列表；(b)一种分离多肽，该多肽包括与序列表中多肽序列具有至少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)序列表中列出的多肽序列；以及(f)一种分离多肽，该多肽具有或包括与序列表所列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。
本发明所述多肽是表II中基因家族的成员。因此根据表III和V中的理由，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，本发明所述多肽具有表I中基因的至少一种生物学活性。
本发明所述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。所述多肽可以是从标准多肽通过添加、缺失及取代变化而来，这些变化可以是保守或非保守的，或其任何组合。具体优选变体为这样的多肽，其中，例如，以任一组合插入、取代或缺失50～30、30～20、20～10、10～5、5～3、3～2、2～1个氨基酸。
本发明所述多肽的优选片段包括这样的分离多肽，该分离多肽包括其中含有来自序列表所列氨基酸序列的至少30、50或100个连续氨基酸的氨基酸序列，或者这样的分离多肽，该分离多肽包括其中含有将序列表所列氨基酸序列截短或缺失至少30、50或100个连续氨基酸的氨基酸序列。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。另外优选的片段是在动物体，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所述多肽片段制备本发明中相应的全长多肽；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，或者在重组过程中用来保持稳定的一段额外的氨基酸序列。
本发明所述多肽可以任何适当的方式制备，例如可以分离自天然来源的材料，分离自含表达系统(见下文)的基因工程宿主细胞，或者化学合成，例如使用自动肽合成仪，或者上述方法的组合。制备所述多肽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多核苷酸；(c)一种分离多核苷酸，该多核苷酸与序列表中列出的多核苷酸之间具有至少95％，96％，97％，98％，或99％的同一性；(d)序列表中列出的分离多核苷酸；(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)一种分离多核苷酸，其中包含编码序列表中多肽的多核苷酸序列；(g)一种分离的多核苷酸，其具有如下核苷酸序列所述序列编码的多肽与序列表中多肽序列之间具有至少95％，96％，97％，98％，或99％的同一性；(h)一种分离多核苷酸，该多核苷酸编码序列表中的多肽；(i)一种分离多核苷酸，该多核苷酸具有或包含与序列表所列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段分离的多核苷酸，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至少15、30、50或100个来自序列表中所列序列的连续核苷酸；或者所述分离的多核苷酸包括如下序列所述序列具有序列表中序列截短或缺失了至少30、50或100个连续核苷酸的序列。
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变体，包括含1个或多个单个核苷酸多态性(SNPs)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多肽变体的多核苷酸即所述多肽变体中包含序列表中的氨基酸序列，并且该氨基酸序列中以任一组合取代、删除或添加了50～30、30～20、20～10、10～5、5～3、3～2、2～1或1个氨基酸残基的多肽变体。
另一方面，本发明提供了本发明所述DNA序列的RNA转录物的多核苷酸。因此，本发明提供了具有下述特征的RNA多核苷酸(a)其中包括编码序列表中多肽的DNA序列的RNA转录物；(b)其本身为编码序列表中多肽的DNA序列的RNA转录物；(c)其中包括序列表中DNA序列的RNA转录物；或者(d)其本身是序列表中DNA序列的RNA转录物；以及与其互补的RNA多核苷酸。
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编码序列相同，或者它也可以是序列表中序列之外的序列，由于遗传密码的丰余性(简并性)，这些序列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中基因家族的其他蛋白相关，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期望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，或者可以用公知或商业化技术合成。
当将本发明所述多核苷酸用于重组生产本发明所述多肽时，所述多核苷酸可以包括成熟多肽的编码序列本身，或者与其他编码序列位于同一阅读框的成熟多肽的编码序列，例如编码前导或分泌序列、前-、原-、前原-蛋白序列、或其他融合肽部分的序列。例如，有助于融合多肽纯化的标记序列可以被编码。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，以及见Gentz等，Proc Natl AcadSci USA(1989)86821-824一文中的描述，或者为一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所述多肽的全长cDNA及基因组克隆，以及可以用来分离其他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)的其他基因的cDNA及基因组克隆(包括编码人源平行进化同源物(paralogs)的基因以及其他物种来源的直向同源物(orthologs)及平行进化同源物的基因)。优选的探针及引物通常包括至少15个核苷酸，优选地，至少30个核苷酸以及可以具有至少50个，如果不是至少100个核苷酸的话。具体优选探针为30～50个核苷酸。具体优选的引物为20～25个核苷酸。
编码本发明所述多肽的多核苷酸，包括来自其他物种的同系物，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(pH7.6)，5xDenhardt′s溶液、10％葡聚糖硫酸酯、以及20mg/ml变性剪切后的鲑鱼精DNA；然后在65℃下用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，多数情况下，分离的cDNA序列是不完整的，因此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”(多聚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合成过程中不能完成对mRNA模板的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)。该技术近来的改进，以Marathon(商标名)技术(Clontech Laboratories Inc.)为代表，例如已经大大简化了较长cDNA的筛选。在Marathon(商标名)技术中，cDNA由提取自选择组织的mRNA制备而得到，并且在每个末端都连接上“衔接头(adaptor)”序列。然后，结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，也就是说，设计在扩增产物内部退火的引物(通常一个为衔接头特异性引物，该引物与衔接头序列的3′端再退火，另一引物为基因特异性引物，该引物与已知基因序列的5′端再退火)。然后，用DNA测序仪分析该反应产物，通过下述方法构建全长cDNA即将产物与现有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通常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所述多肽。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 MolecularBiology(1986)and Sambrook et al.(ibis)。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和草地夜蛾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。
大量的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、嗜菌体、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，以及来源其组合的载体，例如源自质粒及嗜菌体遗传元件的载体，例如粘粒及嗜菌粒。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。
如果本发明所述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，那么就回收培养基以回收及纯化多肽。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所述多肽，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。
本发明所述多肽可以用作诊断试剂，检测相关基因中的突变。突变形式的基因可以通过cDNA或基因组序列的序列表中的多核苷酸来鉴定，且其与功能紊乱相关。本发明将提供一诊断工具，该诊断工具可以增加，或确定，疾病或疾病易感性的诊断，这些疾病由基因的低表达、过表达或变化的时空表达引起。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的方法进行酶扩增，或者用其他扩增技术。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或者插入。通过将扩增DNA与标记后的表1中基因的核苷酸序列杂交检测点突变。用RNA酶消化或熔解温度的差异从错配的双螺旋体中区分出完全匹配的序列。还可以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)检测DNA序列的差异。还可以用核酸酶保护试验检测出特定位点上的序列变化，所述方法例如RNA酶及S1保护或者化学切割方法(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，并且可以用来发现分子遗传学中的大量问题，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他文献。
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。多核苷酸数量的表达减少或增加可以用本领域熟知的任一方法在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印迹法及其他杂交方法。分析技术还可以用于测定蛋白水平，例如本发明所述多肽在来自宿主的样本中的含量，这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，其中包括(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)抗本发明所述多肽的抗体，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，具体为本发明所述疾病。
本发明所述多核苷酸序列对于染色体定位研究很有价值。将序列表中序列特异性地靶向，且杂交到单个人源染色体特定位点上。在本发明的染色体上对相关序列作图是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点上，就可以在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 Johns HopkinsUniversity 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.，andGoodfellow，P.，(1994)一种构建全基因组放射杂交图谱的方法，NatureGenetics 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 radiation hybrid 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中的每一个都包括保存在仓鼠背景(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，表示目的基因的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。通过检测编码多肽的mRNA，所述研究可以确定本发明所述多核苷酸的表达模式，这样可以通过检测编码肽的mRNA为组织中所编码的多肽的表达模式提供启示。所用的技术为本领域熟知，包括对排列在载网上的克隆的原位杂交技术，例如cDNA微阵列杂交(Schena et al，Science，270，467-470，1995 andShalon et al，Genome Res，6，639-645，1996)以及核苷酸扩增技术如PCR。优选方法使用Perkin Elmer公司提供的TAQMAN(商标名)技术。这些试验的结果可以为器官中多肽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，所述基因具有多肽编码的潜在或调节性突变方面的改变)所编码的mRNA的表达模式间的对比研究，可以为本发明所述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、空间或单纯量上的变化。
本发明另一方面还涉及抗体。本发明所述多肽或其片段，或表达它们的细胞，都可以用作制备抗体的免疫原，以制备针对本发明所述多肽的免疫特异性抗体。“免疫特异性”一词是指所述抗体与本发明所述多肽间的亲和力明显大于其与现有技术中其他相关多肽间的亲和力。
抗本发明所述多肽的抗体可以通过常规方法向动物，优选非人动物，施用多肽或含表位片段、或细胞获得。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 CancerTherapy，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所述多肽的单链抗体。另外，转基因鼠，或其他生物，包括其他哺乳动物，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。抗本发明所述多肽的抗体也尤其可以用来治疗本发明所述疾病。
本发明所述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，该方法包括用本发明所述多肽接种哺乳动物，使所述哺乳动物足以产生抗体和/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所述多肽，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包裹在颗粒中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。由于多肽可以在胃中消化，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张(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他本领域已知系统。剂量要根据疫苗的比活性来确定，根据常规经验也可以容易地确定。
本发明所述多肽具有1种或多种与1种或多种病理状态有关的生物功能，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)Chapter5(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。替换地，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，所述方法使用适于带有多肽细胞的检测系统。通常在存在已知激动剂的情况下测定活性抑制剂，观察候选化合物存在时激动剂的活化效果。另外，筛选方法可以简单地包括将候选化合物与含本发明所述多肽的溶液混合，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。
本发明所述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部分和表I中基因的多肽形成的融合蛋白，如上所述，也可用于高流通量筛选试验，来鉴定本发明所述多肽的拮抗剂(see D.Bennett et al.，J Mol Recognition，852-58(1995)；and K.Johansonet 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，检测所加入的化合物对细胞中mRNA及多肽的产量的影响。例如，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连接型多肽的水平。用该方法能从适当操作后的细胞或组织中筛选出可抑制或增加多肽产量的试剂(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所述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，其中所述多肽用放射性同位素(例如，碘125)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，以及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。其他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。完成该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，可以是所述多肽的底物，受体，酶等，例如配体片段、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。其他有用的转基因动物为所谓的“敲除(knock-out)”动物，其中本发明所述多肽的且被细胞中内源DNA序列编码的动物直向进化同源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。转基因动物技术还赋予一完整的动物表达-克隆系统，其中导入的基因被表达生成大量本发明所述多肽。
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)表达本发明所述多肽的重组细胞；(c)表达本发明所述多肽的细胞膜；或者(d)抗本发明所述多肽的抗体；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的产物或其他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，那么就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、基因操作或其他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。
“分泌蛋白的活性或者分泌多肽的活性”或者“分泌蛋白的生物活性或者分泌多肽的生物活性”是指所述分泌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。
“分泌蛋白基因”是指包含了任一附着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，DNA为单链和双链区的混合体，单链及双链RNA，以及由单链和双链区形成的RNA混合体，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及双链区的混合体。此外，“多核苷酸”是指三链区，包含RNA或DNA或者同时包含二者。术语“多核苷酸”还包括含1个或多个修饰碱基的DNA或RNA以及为稳定或其他原因对骨架修饰后的DNAs或RNA。“修饰”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、酶促或代谢方式修饰的形式，以及以病毒及细胞为特征的化学形式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(即肽等排物(isostere))彼此相连的氨基酸的任一多肽。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种基因编码氨基酸外的氨基酸。“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和羧基末端。应该理解的是同一类修饰可以同等程度或不同程度出现在特定多肽的数个位点。另外，特定的多肽可以包括多种类型的修饰。多肽可以是分支状的(遍在蛋白化的结果)，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。所述修饰包括乙酰化、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、共价连接磷脂酸肌醇(phosphotidylinositol)、交联、环化、形成二硫键、去甲基化、生成共价交联、生成胱氨酸、生成焦谷氨酸、甲酰化、γ-羧化、糖基化、GPI锚定形成、羟基化、碘化、甲基化、豆蔻酰化、氧化、蛋白酶处理、磷酸化、异戊二烯化、外消旋化、硒代化(selenoylation)、磺化、转运-RNA介导的蛋白添加氨基酸如精氨酸化，以及遍在蛋白化(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 CovalentModification of Proteins，B.C.Johnson，Ed.，Academic Press，New York，1983；Seifter et al.，“Analysis for protein modifications andnonprotein cofactors”，Meth Enzymol，182，626-646，1990，and Rattanetal.，“Protein SynthesisPosttranslational Modifications andAging”，Ann NY Acad Sci，663，48-62，1992)。
多肽序列“片段”是指比参考序列短但是基本保留了与参考多肽同样的生物功能或活性的多肽序列。多核苷酸序列“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，但是基本保留了参考多核苷酸或参考多肽的特性。多核苷酸的常见变体在核苷酸序列上不同于参考的多核苷酸。变体核苷酸序列的改变可能导致也可能不导致由所述参考多核苷酸编码的多肽氨基酸序列的变化。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，改变是有限度的从而使参考多肽的序列与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任一组合的1个或多个取代、插入、缺失而在氨基酸序列上不同。取代或插入的氨基酸残基可以是也可以不是遗传密码子编码的氨基酸残基。常见的保守取代包括Gly，Ala；Val，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，或者也可以是天然生成的但不为人所知的变体。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的2个或多个备选形式基因中的一种形式的基因。
“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单个核苷酸位置上核苷酸的可变性的发生。SNP可发生于基因组的一基因内或基因间区中。SNPs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。其中的一普通引物用来与待分析的多态性反相互补。该普通引物从多态性碱基起为50-1500个碱基。另外两个(或多个)引物除了最后的3’碱基为与构成多态性的2个(或多个)等位基因之一匹配而摆动(wobble)外是相同的。然后在样本DNA上进行两个(或多个)PCR反应，每个PCR反应都使用上述普通引物和1个等位特异性引物。
本发明中的“剪接变体”是指由这样的RNA分子制备得到的cDNA分子，所述RNA分子最初从同一基因组的DNA序列转录而来，但是其经过了可选择性的RNA剪接。可选择性的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，这样就会制备出不只1个的mRNA分子，其中的每一个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精确对应，或两多核苷酸序列之间核苷酸与核苷酸的精确对应。
“％同一性”-对于不完全对应的序列，可以测定“％同一性”。通常，为得到序列间最大相关程度要将待比较的两序列对齐。这其中包括为提高对齐程度在其中的1个序列插入或者在两个序列中都插入“间隙”。可以在所比序列全长范围内测定％同一性(称为整体对齐)，这特别适用于长度相等或非常近似的序列，或者也可以在较短的确定长度的序列的范围内测定(称为局部对齐)，这更适用于不等长序列。
“相似性”是对两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，不仅将确切对应的计算在内(如同一性的计算)，而且还要把所比序列中不确切对应的计算在内，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”，然后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，version 9.1(Devereux J et al，Nucleic Acids Res，12，387-395，1984，available from Genetics ComputerGroup，Madison，Wisconsin，USA)中的程序，例如程序BESTFIT和GAP，可用来测定两核苷酸序列间的％同一性以及两多肽序列间的％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多核苷酸或两多肽序列，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将两序列对齐，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，在全长序列上对齐。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齐时测定％同一性和相似性。
用于测定序列间同一性和/或相似性的其他程序也为本领域所已知，例如BLAST程序家族(Altschul S F et al，J Mol Biol，215，403-410，1990，Altschul S F et al，Nucleic Acids Res.，25389-3402，1997，availablefrom the National Center for Biotechnology Information(NCBI)，Bethesda，Maryland，USA and accessible through the home page of theNCBI at www.ncbi.nlm.nih.gov)和FASTA(Pearson W R，Methods inEnzymology，183，63-99，1990；Pearson W R and Lipman D J，Proc NatAcad Sci USA，85，2444-2448，1988，available as part of the WisconsinSequence Analysis Package)。
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程序测定多核苷酸或多肽查询序列与多核苷酸或多肽标准序列之间的％同一性，其中将所述查询序列与所述参考序列最优地对齐，并将程序的参数值设为如上缺省值。
“同一性指数”是指序列相关程度的测量，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，除了候选多核苷酸序列内平均每100个核苷酸中有5个与参考序列不同。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序列5′或3′末端或者两末端之间的任一位置，可以单个核苷酸的形式散布在参考序列的核苷酸中或者也可以1个或多个连续核苷酸成组的方式出现在参考序列内。换句话说，为了得到一与参考序列间同一性指数为0.95的多核苷酸序列，可以对参考序列的核苷酸平均每100个中的5个缺失、替换或插入，或其任一组合，如上文所述。必要时同样可采用其他同一性指数，例如0.96，0.97，0.98和0.99。
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，除了候选多肽序列内平均每100个氨基酸中有5个与参考序列不同。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序列的氨基或羧基末端或者两末端之间的任一位置，可以单个氨基酸的形式散布在参考序列的氨基酸中或者也可以1个或多个连续氨基酸成组的方式出现在参考序列内。换句话说，为了得到一与参考序列间同一性指数为0.95的多肽序列，可以对参考序列的氨基酸平均每100个中的5个缺失、取代或插入，或其任一组合，如上文所述。必要时同样采用其他同一性指数，例如0.96，0.97，0.98和0.99。
特定数目核苷酸或氨基酸差异间的相关程度及同一性指数可以表述为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，以及其中当xa和I的乘积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”是本领域的一广义词汇，意指一与参考序列间有很高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上述的测定同一性和/或相似性的方法对相关程度定量。属于这一广义词汇的有“直向进化同源物”及“平行进化同源物”。“直向进化同源物”是指另一物种中与所述多核苷酸或多肽功能等价的多核苷酸或多肽。“平行进化同源物”是指属于功能类似的同一物种中的多核苷酸或多肽。
“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II(续)
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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；seeSchmittgen T.D.et al.，Analytical Biochemistry 285194-204，2000)以及从各种人组织中制备的人cDNA测定基因mRNA的组织特异性的定量表达模式。使用序列表中的第一个核酸序列为每个基因设计基因特异性PCR引物。结果表示为每种组织1ng mRNA汇集物中检测到的每一特定基因的mRNA的拷贝数。对每一组织RNA都进行两次mRNA平行测量。
基因名称sbg237163脂肪酶
基因名称sbg251170CEAa
在每种基因的第一个表中，显示了对各种人组织中鉴定基因(gene ofidentification(GOI))mRNA的两次重复检测结果(第2列和第3列)。表中显示了各种组织RNA中两次重复检测的平均GOI mRNA拷贝数(第4列)。检测了各种组织RNA中18S rRNA的平均值(第5列)并用以标准化。为使每种组织具有相同的18S rRNA的50ng的量，50ng除以检测到的各种组织的18S rRNA的量(第5列)，计算标准化系数(第6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7列)。
倍数变化显示在每种基因的第二个表中，该表仅对疾病组织(其有正常的对照物)进行了计算。在倍数变化列中没有对照物的所有标本显示有空白。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，任何正常标本后没有倍数变化数值。对于成对的肿瘤患者(结肠，肺和乳腺)，每种肿瘤与其特定的正常对照物相比较。如果不存在吻合的正常/疾病患者对，那么每种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，在获得Alzheimer脑的同一患者中正常脑是不适用的。在进行倍数变化的检测中，应用3个正常脑标本和4个Alzheimer脑标本。将3个正常标本进行平均，每个Alzheimer标本再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)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人免疫缺陷病毒HSV单纯疱疹病毒HPV人乳头瘤病毒基因名称sbg389686WNT15a该基因在脑和树突细胞中高表达。脑表达可能是由于神经胶质细胞存在表达。RA和OA滑膜和树突细胞中该基因的表达提示该种蛋白可能在这些疾病中起作用。在缺血和扩张的心脏中该蛋白的下调提示替换该蛋白可能有治疗作用。
基因名称sbg389686WNT15a
基因名称sbg236015脂肪酶在中性粒细胞和嗜酸性粒细胞中该基因的高表达提示其免疫系统的功能。
在RA和OA滑膜和1/3OA骨标本中也可见该基因的表达。这提示236015参与RA和OA。其在皮肤中高表达同时在中性粒细胞和嗜酸性粒细胞中表达提示其可能参与皮肤的免疫病理过程，即嗜酸性粒细胞增多，牛皮癣和湿疹。自在嗜酸性粒细胞中该基因的表达也提示其参与过敏反应。在中性粒细胞的该基因的表达提示其在抗感染中的作用。
基因名称sbg236015脂肪酶
基因名称sbg417005层粘连蛋白该基因在腺样组织(adenoid)，扁桃腺和B细胞中表达同时在RA/OA标本和哮喘肺(1/4)中确有表达提示其与这些疾病有关。在脑中高表达并且在阿尔茨海默氏病中过表达提示其在AD中的作用。在HSV感染细胞中其表达下调提示潜在的宿主细胞因素。在结肠和肺正常/肿瘤对中表达，但在正常组织中无确定的表达提示免疫细胞的浸润(infiltrates)。

基因名称sbg417005层粘连蛋白
基因名称sbg425649激酶a其在嗜中性粒细胞和嗜酸性粒细胞中高表达提示其在免疫系统中的功能如参与过敏反应和抗感染。其在T细胞中表达较低。在2/3的OA骨标本中表达提示其在OA中的作用。其在直肠和骨骼肌中高表达，但其中的作用尚属未知。
基因名称sbg425649激酶a
基因名称sbg419582原钙粘着蛋白其存在脑特异性表达。其与阿尔茨海默氏病并无相关性。在RA和OA滑膜中低表达但在免疫细胞中无确定的表达。在心脏疾病中其表达略微上调。在肺肿瘤(1/4)和乳腺肿瘤(1/4)中过表达。
基因名称sbg419582原钙粘着蛋白
基因名称sbg453915TECTORINa其总体表达很低。在女性生殖组织中的表达提示了其是由这些组织类型分泌的一种蛋白。
基因名称sbg453915TECTORINa
基因名称SBh385630antiinflam在腺样组织，扁桃腺和T细胞中的表达提示其在免疫系统中的作用。在GI组织中的表达提示其在消化系统中的作用和在GI疾病如IBD中的潜在作用。在肺肿瘤(1/4)和结肠肿瘤(1/4)中的过表达提示其在肺和结肠肿瘤中的作用。在缺血性和扩张性心脏标本中表达增加提示其在心血管疾病(与心脏肥大一致的疾病)中的作用。其在全脑中表达，而不是只局限在下丘脑，小脑和皮质。
基因名称SBh385630antiinflam
基因名称sbg471005nAChR
其在免疫细胞中表达，在OA和RA滑膜中有确定的表达提示其在该病中的作用。
其在全脑中表达，但不存在于皮质，小脑或下丘脑中提示其在脑中局限性的表达。

基因名称sbg471005nAChR
基因名称sbg442445PROa其在B细胞中高表达和在其它类型免疫细胞中表达提示其在免疫系统中的功能。在RA和OA中有确定的表达提示其在该病中的作用。在感染有HIV的细胞中其表达增加2倍提示其可能成为HIV感染的标志物。在除皮质或小脑外的全脑中表达提示其在脑中是局限性表达。
基因名称sbg442445PROa
基因名称sbg456548CytoRa其在腺样组织/扁桃腺和树突细胞中高表达。在刺激后的骨髓中过表达。综合起来，这些数据提示其在免疫功能中的作用。在胃肠道中的表达提示其在胃肠道(GI)系统疾病诸如IBD，Chron’s病等疾病中的潜在作用。
基因名称sbg456548CytoRa
基因名称sbg442358PROa其在多种类型免疫细胞和刺激后的骨髓细胞和胸腺中高表达提示其在免疫系统中的功能。在乳腺肿瘤(1/4)中过表达。在RA和OA中表达和在免疫细胞中的确定表达提示其在这些疾病中的作用。在心脏疾病中的过表达提示其在心血管疾病中的作用。在HSV感染细胞中表达下调提示可能的宿主细胞因素。
基因名称sbg442358PROa
表V.其他以特异性组织中mRNA表达为基础的疾病
序列表<110> 史密丝克莱恩比彻姆公司(SMITHKLINE BEECHAM CORPORATION)史密斯克莱·比奇曼公司(SMITHKLINE BEECHAM p.l.c.)葛兰素基团公司(GLAXO GROUP LTD.)<120> 新型化合物<130> GP50029<140> 待定<141> 2001-06-22<150> 60/213，161<151> 2000-06-22<150> 60/213，156<151> 2000-06-22<160> 44<170> FastSEQ for Windows Version 4.0<210> 1<211> 1383<212> DNA<213> 人(Homo sapiens)<400> 1atgcttggaa tttggattgt tgcattcttg ttctttggca catcaagagg aaaagaagtt 60tgctatgaaa ggttagggtg tttcaaagat ggtttaccat ggaccaggac tttctcaaca 120gagttggtag gtttaccctg gtctccagag aagataaaca ctcgtttcct gctctacact 180atacacaatc ccaatgccta tcaggagatc agtgcggtta attcttcaac tatccaagcc 240tcatattttg gaacagacaa gatcacccgt atcaacatag ctggatggaa aacagatggc 300aaatggcaga gagacatgtg caatgtgttg ctacagctgg aagatataaa ttgcattaat 360ttagattgga tcaacggttc acgggaatac atccatgctg taaacaatct ccgtgttgtt 420ggtgctgagg tggcttattt tattgatgtt ctcatgaaaa aatttgaata ttccccttct 480aaagtgcact tgattggcca cagcttggga gcacacctgg ctggggaagc tgggtcaagg 540ataccaggcc ttggaagaat aactgggttg gacccagctg ggccattttt ccacaacact 600ccaaaggaag tcaggctaga cccctcggat gccaactttg ttgacgttat tcatacaaat 660gcagctcgca tcctctttga gcttggtgtt ggaaccattg atgcttgtgg tcatcttgac 720ttttacccaa atggagggaa gcacatgcca ggatgtgaag acttaattac acctttactg 780aaatttaact tcaatgctta caaaaaagaa atggcttcct tctttgactg taaccatgcc 840cgaagttatc aattttatgc tgaaagcatt cttaatcctg atgcatttat tgcttatcct 900tgtagatcct acacatcttt taaagcaggt acatgtgtag gatgtgcaga tttgttacat 960aggatagata agataggaag tcatacttcc catgtgtttt taaccctttc tctccctttc 1020cttcttgttt ccttatatct aggttggagg cacaaattgt ctgttaaact cagtggaagc 1080gaagtcactc aaggaactgt ctttcttcgt gtaggcgggg cagttaggaa aactggggag 1140tttgccattg tcagtggaaa acttgagcca ggcatgactt acacaaaatt aatcgatgca 1200gatgttaacg ttggaaacat tacaagtgtt cagttcatct ggaaaaaaca tttgtttgaa 1260gattctcaga ataagttggg agcagaaatg gtgataaata catctgggaa atatggatat 1320aaatctacct tctgtagcca agacattatg ggacctaata ttctccagaa cctgaaacca 1380tgc 1383<210> 2<211> 927<212> DNA<213> 人(Homo sapiens)<400> 2atgccgttcc tgcagctgaa agggagagca acacctccat cctggagaca cgatagccgc 60tcacttgttc acctgctgga cggcaaggag ggcgtgtggg acaccacggg ctatgcctta 120gggagcagag aatcattgaa tcctgacatg gggattggtg acccacatgg acacagcact 180gtccacacca gggaagcagg cactgcctgt ccattacagc ttctaggtgc tcgggaggcc 240agtctgctgg cctgtgggat ctgccaggcc tctggccaaa tcttcatcac ccaaaccctg 300gggatcaagg gatatcggac tgtcgtggcc ctggataagg tccctgagga tgttcaggaa 360tacagctggt actggggtgc aaacgacagc gcaggaaaca tgattatcag ccacaaaccg 420cccagtgccc agcagcctgg gcccatgtac actggcaggg agagagtgaa cagagaaggc 480agcctgttga tcaggccgac tgcattaaat gacacgggaa actacactgt tcgggtggtt 540gcaggcaatg agacccaaag agcaaccggc tggctggagg ttctagatgg gcccgactat 600gtgctgctga ggagcaatcc tgatgatttc aacggcattg tgacagctga gatcggctcc 660caagtggaaa tggagtgtat ctgctattcc ttcctggatc tcaagtacca ctggatccac 720aatggctccc tcctgaactt ctcagatgca aagatgaacc tctcgagtct tgcctgggag 780cagatgggcc gttaccgatg cactgtggag aaccccgtga cacagctgat catgtacatg 840gacgtcagga tccaggcccc ccatgagtgc agcagctccc ctccaggctc atgctttgca 900catctccctg cctccatgcc ctgctag 927<210> 3<211> 1374<212> DNA<213> 人(Homo sapiens)<400> 3atggaccttt ccagacccag atggagcctg tggaggaggg tcttcctcat ggccagtctg 60ctggcctgtg ggatctgcca ggcctctggc caaatcttca tcacccaaac cctggggatc 120aagggatatc ggactgtcgt ggccctggat aaggtccctg aggatgttca ggaatacagc 180tggtactggg gtgcaaacga cagcgcagga aacatgatta tcagccacaa accgcccagt 240gcccagcagc ctgggcccat gtacactggc agggagagag tgaacagaga aggcagcctg 300ttgatcaggc cgactgcatt aaatgacacg ggaaactaca ctgttcgggt ggttgcaggc 360aatgagaccc aaagagcaac cggctggctg gaggttctag agttgggaag caatctgggc 420atctccgtca atgccagctc cctggtggag aacatggatt ctgtggctgc tgactgcctc 480acaaatgtca ccaacatcac gtggtatgtg aatgatgtgc ctacctctag tagtgaccgg 540atgacaattt ccccagacgg caagaccctc gtcatcctca gggtcagccg ctatgacaga 600acaattcagt gcatgataga gagtttccca gagatctttc agagaagtga acgcatctct 660ctgactgtgg cctatgggcc cgactatgtg ctgctgagga gcaatcctga tgatttcaac 720ggcattgtga cagctgagat cggctcccaa gtggaaatgg agtgtatctg ctattccttc 780ctggatctca agtaccactg gatccacaat ggctccctcc tgaacttctc agatgcaaag 840atgaacctct cgagtcttgc ctgggagcag atgggccgtt accgatgcac tgtggagaac 900cccgtgacac agctgatcat gtacatggac gtcaggatcc aggcccccca tgagtgtcct 960cttccttcag ggatcttacc tgttgtccac agagatttct ccatctcagg atccatggtg 1020atgttcctca tcatgctgac agtgctgggt ggcgtttaca tctgtggagt cctgatccat 1080gctctgatca accactactc aatcaggtgc cctcattgct ctgggacaag ggtgggatgt 1140tggctggggg ctgggactca ggagccagcc ctccctccag aggggaagca gagccagaag 1200gggagggata agccaggaac taggttgtca gggatcatct ggggcagaca gatcagcccc 1260caggacctga agctgatggg agcaagagag ggtttagagt cggccatggt tctaaatagc 1320tgtggggttt cttctagcaa cttcccttct ctttgtgttt ataagggata ttaa 1374<210> 4<211> 2115<212> DNA<213> 人(Homo sapiens)<400> 4atgctccatg atgggttgac tgcacctgat gggtgtggaa tctacagcct gaccgggcgg 60gaagtcctga cgcccttccc aggattgggc actgcggcag ccccggcaca gggcggggcc 120cacctgaagc agtgtgacct gctgaagctg tcccggcggc agaagcagct ctgccggagg 180gagcccggcc tggctgagac cctgagggat gctgcgcacc tcggcctgct tgagtgccag 240tttcagttcc ggcatgagcg ctggaactgt agcctggagg gcaggatggg cctgctcaag 300agaggcttca aagagacagc tttcctgtac gcggtgtcct ctgccgccct cacccacacc 360ctggcccggg cctgcagcgc tgggcgcatg gagcgctgca cctgtgatga ctctccgggg 420ctggagagcc ggcaggcctg gcagtggggc gtgtgcggtg acaacctcaa gtacagcacc 480aagtttctga gcaacttcct ggggtccaag agaggaaaca aggacctgcg ggcacgggca 540gacgcccaca atacccacgt gggcatcaag gctgtgaaga gtggcctcag gaccacgtgt 600aagtgccatg gcgtatcagg ctcctgtgcc gtgcgcacct gctggaagca gctctccccg 660ttccgtgaga cgggccaggt gctgaaactg cgctatgact cggctgtcaa ggtgtccagt 720gccaccaatg aggccttggg ccgcctagag ctgtgggccc ctgccaggca gggcagcctc 780accaaaggcc tggccccaag gtctggggac ctggtgtaca tggaggactc acccagcttc 840tgccggccca gcaagtactc acctggcaca gcaggtaggg tgtgctcccg ggaggccagc 900tgcagcagcc tgtgctgcgg gcggggctat gacacccaga gccgcctggt ggccttctcc 960tgccactgcc aggtgcagtg gtgctgctac gtggagtgcc agcaatgtgt gcaggaggag 1020cttgtgtaca cctgcaagca ctagatgggc cctgtggggt tcccgaggca gtgccaggga 1080gccttctttg agagcagccc tgggcagacc agggcccgcc tgaccgggcg ggaagtcctg 1140acgcccttcc caggattggg cactgcggca gccccggcac agggcggggc ccacctgaag 1200cagtgtgacc tgctgaagct gtcccggcgg cagaagcagc tctgccggag ggagcccggc 1260ctggctgaga ccctgaggga tgctgcgcac ctcggcctgc ttgagtgcca gtttcagttc 1320cggcatgagc gctggaactg tagcctggag ggcaggatgg gcctgctcaa gagaggcttc 1380aaagagacag ctttcctgta cgcggtgtcc tctgccgccc tcacccacac cctggcccgg 1440gcctgcagcg ctgggcgcat ggagcgctgc acctgtgatg actctccggg gctggagagc 1500cggcaggcct ggcagtgggg cgtgtgcggt gacaacctca agtacagcac caagtttctg 1560agcaacttcc tggggtccaa gagaggaaac aaggacctgc gggcacgggc agacgcccac 1620aatacccacg tgggcatcaa ggctgtgaag agtggcctca ggaccacgtg taagtgccat 1680ggcgtatcag gctcctgtgc cgtgcgcacc tgctggaagc agctctcccc gttccgtgag 1740acgggccagg tgctgaaact gcgctatgac tcggctgtca aggtgtccag tgccaccaat 1800gaggccttgg gccgcctaga gctgtgggcc cctgccaggc agggcagcct caccaaaggc 1860ctggccccaa ggtctgggga cctggtgtac atggaggact cacccagctt ctgccggccc 1920agcaagtact cacctggcac agcaggtagg gtgtgctccc gggaggccag ctgcagcagc 1980ctgtgctgcg ggcggggcta tgacacccag agccgcctgg tggccttctc ctgccactgc 2040caggtgcagt ggtgctgcta cgtggagtgc cagcaatgtg tgcaggagga gcttgtgtac 2100acctgcaagc actag 2115<210> 5<211> 1086<212> DNA<213> 人(Homo sapiens)<400> 5atgaagcccc tgaggaggcc ccttcccttc atttgcccct caccaccatc cccaaggctc 60acctgtctcc ctcctctcgc tctctctagc ctgaccgggc gggaagtcct gacgcccttc 120ccaggattgg gcactgcggc agccccggca cagggcgggg cccacctgaa gcagtgtgac 180ctgctgaagc tgtcccggcg gcagaagcag ctctgccgga gggagcccgg cctggctgag 240accctgaggg atgctgcgca cctcggcctg cttgagtgcc agtttcagtt ccggcatgag 300cgctggaact gtagcctgga gggcaggatg ggcctgctca agagaggctt caaagagaca 360gctttcctgt acgcggtgtc ctctgccgcc ctcacccaca ccctggcccg ggcctgcagc 420gctgggcgca tggagcgctg cacctgtgat gactctccgg ggctggagag ccggcaggcc 480tggcagtggg gcgtgtgcgg tgacaacctc aagtacagca ccaagtttct gagcaacttc 540ctggggtcca agagaggaaa caaggacctg cgggcacggg cagacgccca caatacccac 600gtgggcatca aggctgtgaa gagtggcctc aggaccacgt gtaagtgcca tggcgtatca 660ggctcctgtg ccgtgcgcac ctgctggaag cagctctccc cgttccgtga gacgggccag 720gtgctgaaac tgcgctatga ctcggctgtc aaggtgtcca gtgccaccaa tgaggccttg 780ggccgcctag agctgtgggc ccctgccagg cagggcagcc tcaccaaagg cctggcccca 840aggtctgggg acctggtgta catggaggac tcacccagct tctgccggcc cagcaagtac 900tcacctggca cagcaggtag ggtgtgctcc cgggaggcca gctgcagcag cctgtgctgc 960gggcggggct atgacaccca gagccgcctg gtggccttct cctgccactg ccaggtgcag 1020tggtgctgct acgtggagtg ccagcaatgt gtgcaggagg agcttgtgta cacctgcaag 1080cactag1086<210> 6<211> 1098<212> DNA<213> 人(Homo sapiens)<400> 6atgtggctgc ttttaacaac aacttgtttg atctgtggaa ctttaaatgc tggtggattc 60cttgatttgg aaaatgaagt gaatcctgag gtgtggatga atactagtga aatcatcatc 120tacaatggct accccagtga agagtatgaa gtcaccactg aagatgggta tatactcctt 180gtcaacagaa ttccttatgg gcgaacacat gctaggagca cagcagatgc aggttatgat 240gtatggatgg gaaacagtcg gggaaacact tggtcaagaa gacacaaaac actctcagag 300acagatgaga aattctgggc ctttagtttt gatgaaatgg ccaaatatga tctcccagga 360gtaatagact tcattgtaaa taaaactggt caggagaaat tgtatttcat tggacattca 420cttggcacta caatagggtt tgtagccttt tccaccatgc ctgaactggc acaaagaatc 480aaaatgaatt ttgccttggg tcctacgatc tcattcaaat atcccacggg catttttacc 540aggttttttc tacttccaaa ttccataatc aaggctgttt ttggtaccaa aggtttcttt 600ttagaagata agaaaacgaa gatagcttct accaaaatct gcaacaataa gatactctgg 660ttgatatgta gcgaatttat gtccttatgg gctggatcca acaagaaaaa tatgaatcag 720agtcgaatgg atgtgtatat gtcacatgct cccactggtt catcagtaca caacattctg 780catataaaac agctttacca ctctgatgaa ttcagagctt atgactgggg aaatgacgct 840gataatatga aacattacaa tcagagtcat ccccctatat atgacctgac tgccatgaaa 900gtgcctactg ctatttgggc tggtggacat gatgtcctcg taacacccca ggatgtggcc 960aggatactcc ctcaaatcaa gagtcttcat tactttaagc tattgccaga ttggaaccac 1020tttgattttg tctggggcct cgatgcccct caacggatgt acagtgaaat catagcttta 1080atgaaggcat attcctaa 1098<210> 7<211> 1194<212> DNA<213> 人(Homo sapiens)<400> 7atgtggcagc ttttagcagc agcatgctgg atgcttcttc ttggatctat gtatggttat 60gacaagaaag gaaacaatgc aaaccctgaa gctaatatga atattagcca gattatttct 120tactggggtt atccttatga agagtatgat gttacaacaa aagatggtta tatccttgga 180atttatagga ttccacatgg aagaggatgc ccagggagga cagctccaaa gcctgctgtg 240tatttgcagc atggcttaat tgcatctgcc agtaactgga tttgcaacct gcccaacaac 300agtttggctt tccttctggc agatagtggt tatgacgtgt ggttggggaa cagccgagga 360aacacttggt ccagaaaaca ccttaaattg tcaccgaaat caccggaata ctgggccttc 420agtttggatg agatggctaa atatgacctt ccagccacaa tcaattttat catagagaaa 480actggacaga agcgactcta ctacgtgggc cactcacaag gcaccaccat agcttttata 540gcattttcta caaacccaga actggctaaa aagattaaga tattttttgc actggctcca 600gttgtcacag ttaaatacac ccaaagtcct atgaaaaaac taacaaccct ttccaggcga 660gtagttaagg tgttgtttgg tgacaaaatg ttccaccctc atacattgtt tgaccaattc 720attgccacca aagtgtgcaa tcgaaagcta ttccgtcgta tttgcagcaa cttcctattt 780actctgagtg gatttgatcc gcaaaactta aatatgagtc gcttggatgt ttatttgtca 840cacaatcctg cgggaacatc tgttcagaat atgctgcact gggctcagct ttaccactct 900gatgaattca gagcttatga ctggggaaat gacgctgata atatgaaaca ttacaatcag 960agtcatcccc ctatatatga cctgactgcc atgaaagtgc ctactgctat ttgggctggt 1020ggacatgatg tcctcgtaac accccaggat gtggccagga tactccctca aatcaagagt 1080cttcattact ttaagctatt gccagattgg aaccactttg attttgtctg gggcctcgat 1140gcccctcaac ggatgtacag tgaaatcata gctttaatga aggcatattc ctaa 1194<210> 8<211> 11118<212> DNA<213> 人(Homo sapiens)<400> 8atggcgaagc ggctctgcgc ggggagcgca ctgtgtgttc gcggcccccg gggccccgcg 60ccgctgctgc tggtcgggct ggcgctgctg ggcgcggcgc gggcgcggga ggaggcgggc 120ggcggcttca gcctgcaccc gccctacttc aacctggccg agggcgcccg catcgccgcc 180tccgcgacct gcggagagga ggccccggcg cgcggctccc cgcgccccac cgaggacctt 240tactgcaagc tggtaggggg ccccgtggcc ggcggcgacc ccaaccagac catccggggc 300cagtactgtg acatctgcac ggctgccaac agcaacaagg cacaccccgc gagcaatgcc 360atcgatggca cggagcgctg gtggcagagt ccaccgctgt cccgcggcct ggagtacaac 420gaggtcaacg tcaccctgga cctgggccag gtcttccacg tggcctacgt cctcatcaag 480tttgccaact caccccggcc ggacctctgg gtgctggagc ggtccatgga cttcggccgc 540acctaccagc cctggcagtt ctttgcctcc tccaagaggg actgtctgga gcggttcggg 600ccacagacgc tggagcgcat cacacgggac gacgcggcca tctgcaccac cgagtactca 660cgcatcgtgc ccctggagaa cggagagatc gtggtgtccc tggtgaacgg acgtccgggc 720gccatgaatt tctcctactc gccgctgcta cgtgagttca ccaaggccac caacgtccgc 780ctgcgcttcc tgcgtaccaa cacgctgctg ggccatctca tggggaaggc gctgcgggac 840cccacggtca cccgccggta ttattacagc atcaaggata tcagcatcgg aggccgctgt 900gtctgccacg gccacgcgga tgcctgcgat gccaaagacc ccacggaccc gttcaggctg 960cagtgcacct gccagcacaa cacctgcggg ggcacctgcg accgctgctg ccccggcttc 1020aatcagcagc cgtggaagcc tgcgactgcc aacagtgcca acgagtgcca gtcctgtaac 1080tgctacggcc atgccaccga ctgttactac gaccctgagg tggaccggcg ccgcgccagc 1140cagagcctgg atggcaccta tcagggtggg ggtgtctgta tcgactgcca gcaccacacc 1200accggcgtca actgtgagcg ctgcctgccc ggcttctacc gctctcccaa ccaccctctc 1260gactcgcccc acgtctgccg ccgctgcaac tgcgagtccg acttcacgga tggcacctgc 1320gaggacctga cgggtcgatg ctactgccgg cccaacttct ctggggagcg gtgtgacgtg 1380tgtgccgagg gcttcacggg cttcccaagc tgctacccga cgccctcgtc ctccaatgac 1440accagggagc aggtgctgcc agccggccag attgtgaatt gtgactgcag cgcggcaggg 1500acccagggca acgcctgccg gaaggaccca agggtgggac gctgtctgtg caaacccaac 1560ttccaaggca cccattgtga gctctgcgcg ccagggttct acggccccgg ctgccagccc 1620tgccagtgtt ccagccctgg agtggccgat gaccgctgtg accctgacac aggccagtgc 1680aggtgccgag tgggcttcga gggggccaca tgtgatcgct gtgcccccgg ctactttcac 1740ttccctctct gccagttgtg tggctgcagc cctgcaggaa ccttgcccga gggctgcgat 1800gaggccggcc gctgcctatg ccagcctgag tttgctggac ctcattgtga ccggtgccgc 1860cctggctacc atggtttccc caactgccaa gcatgcacct gcgaccctcg gggagccctg 1920gaccagctct gtggggcggg aggtttgtgc cgctgccgcc ccggctacac aggcactgcc 1980tgccaggaat gcagccccgg ctttcacggc ttccccagct gtgtcccctg ccactgctct 2040gctgaaggct ccctgcacgc agcctgtgac ccccggagtg ggcagtgcag ctgccggccc 2100cgtgtgacgg ggctgcggtg tgacacatgt gtgcccggtg cctacaactt cccctactgc 2160gaagctggct cttgccaccc tgccggtctg gccccagtgg atcctgccct tcctgaggca 2220caggttccct gtatgtgccg ggctcacgtg gaggggccga gctgtgaccg ctgcaaacct 2280gggttctggg gactgagccc cagcaacccc gagggctgta cccgctgcag ctgcgacctc 2340aggggcacac tgggtggagt tgctgagtgc cagccgggca ccggccagtg cttctgcaag 2400ccccacgtgt gcggccaggc ctgcgcgtcc tgcaaggatg gcttctttgg actggatcag 2460gctgactatt ttggctgccg cagctgccgg tgtgacattg gcggtgcact gggccagagc 2520tgtgaaccga ggacgggcgt ctgccggtgc cgccccaaca cccagggccc cacctgcagc 2580gagcctgcga gggaccacta cctcccggac ctgcaccacc tgcgcctgga gctggaggag 2640gctgccacac ctgagggtca cgccgtgcgc tttggcttca accccctcga gttcgagaac 2700ttcagctgga ggggctacgc gcagatggca cctgtccagc ccaggatcgt ggccaggctg 2760aacctgacct cccctgacct tttctggctc gtcttccgat acgtcaaccg gggggccatg 2820agtgtgagcg ggcgggtctc tgtgcgagag gagggcaggt cggccacctg cgccaactgc 2880acagcacaga gtcagcccgt ggccttccca cccagcacgg agcctgcctt catcaccgtg 2940ccccagaggg gcttcggaga gccctttgtg ctgaaccctg gcacctgggc cctgcgtgtg 3000gaggccgaag gggtgctcct ggactacgtg gttctgctgc ctagcgcata ctacgaggcg 3060gcgctcctgc agctgcgggt gactgaggcc tgcacatacc gtccctctgc ccagcagtct 3120ggcgacaact gcctcctcta cacacacctc cccctggatg gcttcccctc ggccgccggg 3180ctggaggccc tgtgtcgcca ggacaacagc ctgccccggc cctgccccac ggagcagctc 3240agcccgtcgc acccgccact gatcacctgc acgggcagtg atgtggacgt ccagcttcaa 3300gtggcagtgc cacagccagg ccgctatgcc ctagtggtgg agtacgccaa tgaggatgcc 3360cgccaggagg tgggcgtggc cgtgcacacc ccacagcggg ccccccagca ggggctgctc 3420tccctgcacc cctgcctgta cagcaccctg tgccggggca ctgcccggga tacccaggac 3480cacctggctg tcttccacct ggactcggag gccagcgtga ggctcacagc cgaacaggca 3540cgcttcttcc tgcacggggt cactctggtg cccattgagg agttcagccc ggagttcgtg 3600gagccccggg tcagctgcat cagcagccac ggcgcctttg gccccaacag tgccgcctgt 3660ctgccctcgc gcttcccaaa gccgccccag cccatcatcc tcagggactg ccaggtgatc 3720ccgctgccgc ccggcctccc gctgacccac gcgcaggatc tcactccagc catgtcccca 3780gctggacccc gacctcggcc ccccaccgct gtggaccctg atgcagagcc caccctgctg 3840cgtgagcccc aggccaccgt ggtcttcacc acccatgtgc ccacgctggg ccgctatgcc 3900ttcctgctgc acggctacca gccagcccac cccaccttcc ccgtggaagt cctcatcaac 3960gccggccgcg tgtggcaggg ccacgccaac gccagcttct gtccacatgg ctacggctgc 4020cgcaccctgg tggtgtgtga gggccaggcc ctgctggacg tgacccacag cgagctcact 4080gtgaccgtgc gtgtgcccaa gggccggtgg ctctggctgg attatgtact cgtggtccct 4140gagaacgtct acagctttgg ctacctccgg gaggagcccc tggataaatc ctatgacttc 4200atcagccact gcgcagccca gggctaccac atcagcccca gcagctcatc cctgttctgc 4260cgaaacgctg ctgcttccct ctccctcttc tataacaacg gagcccgtcc atgtggctgc 4320cacgaagtag gtgctacagg ccccacgtgt gagcccttcg ggggccagtg tccctgccat 4380gcccatgtca ttggccgtga ctgctcccgc tgtgccaccg gatactgggg cttccccaac 4440tgcaggccct gtgactgcgg tgcccgcctc tgtgacgagc tcacgggcca gtgcatctgc 4500ccgccacgca ccatcccgcc cgactgcctg ctgtgccagc cccagacctt tggctgccac 4560cccctggtcg gctgtgagga gtgtaactgc tcagggcccg gcatccagga gctcacagac 4620cctacctgtg acacagacag cggccagtgc aagtgcagac ccaacgtgac tgggcgccgc 4680tgtgatacct gctctccggg cttccatggc tacccccgct gccgcccctg tgactgtcac 4740gaggcgggca ctgcgcctgg cgtgtgtgac cccctcacag ggcagtgcta ctgtaaggag 4800aacgtgcagg gccccaaatg tgaccagtgc agccttggga ccttctcact ggatgctgcc 4860aaccccaaag gttgcacccg ctgcttctgc tttggggcca cggagcgctg ccggagctcg 4920tcctacaccc gccaggagtt cgtggatatg gagggatggg tgctgctgag cactgaccgg 4980caggtggtgc cccacgagcg gcagccaggg acggagatgc tccgtgcaga cctgcggcac 5040gtgcctgagg ctgtgcccga ggctttcccc gagctgtact ggcaggcccc accctcctac 5100ctgggggacc gggtgtcatc ctacggtggg accctccgtt atgaactgca ctcagagacc 5160cagcggggag atgtctttgt ccccatggag agcaggccgg atgtggtgct gcagggcaac 5220cagatgagca tcacattcct ggagccggca taccccacgc ctggccacgt tcaccgtggg 5280cagctgcagc tggtggaggg gaacttccgg catacggaga cgcgcaacac tgtgtcccgc 5340gaggagctca tgatggtgct ggccagcctg gagcagctgc agatccgtgc cctcttctca 5400cagatctcct cggctgtctt cctgcgcagg gtggcactgg aggtggccag cccagcaggc 5460cagggggccc tggccagcaa tgtggagctg tgcctgtgcc ccgccagcta ccggggggac 5520tcatgccagg aatgtgcccc cggcttctat cgggacgtca aaggtctctt cctgggccga 5580tgtgtccctt gtcagtgcca tggacactca gaccgctgcc tccctggctc tggcgtctgt 5640gtggactgcc agcacaacac cgaaggggcc cactgtgagc gctgccaggc tggcttcgtg 5700agcagcaggg acgaccccag cgccccctgt gtcagctgcc cctgccccct ctcagtgcct 5760tccaacaact tcgccgaggg ctgtgtcctg cgaggcggcc gcacccagtg cctctgcaaa 5820cctggttatg caggtgcctc ctgcgagcgg tgtgcgcccg gattctttgg gaacccactg 5880gtgctgggca gctcctgcca gccatgcgac tgcagcggca acggtgaccc caacttgctc 5940ttcagcgact gcgaccccct gacgggcgcc tgccgtggct gcctgcgcca caccactggg 6000ccccgctgcg agatctgtgc ccccggcttc tacggcaacg ccctgctgcc cggcaactgc 6060acccggtgcg actgtacccc atgtgggaca gaggcctgcg acccccacag cgggcactgc 6120ctgtgcaagg cgggcgtgac tgggcggcgc tgtgaccgct gccaggaggg acattttggt 6180ttcgatggct gcgggggctg ccgcccgtgt gcttgtggac cggccgccga gggctccgag 6240tgccaccccc agagcggaca gtgccactgc cgaccaggga ccatgggacc ccagtgccgc 6300gagtgtgccc ctggctactg ggggctccct gagcagggct gcaggcgctg ccagtgccct 6360gggggccgct gtgaccctca cacgggccgc tgcaactgcc ccccggggct cagcggggag 6420cgctgcgaca cctgcagcca gcagcatcag gtgcctgttc caggcgggcc tgtgggccac 6480agcatccact gtgaagtgtg tgaccactgt gtggtcctgc tcctggatga cctggaacgg 6540gccggcgccc tcctccccgc cattcacgag caactgcgtg gcatcaatgc cagctccatg 6600gcctgggccc gtctgcacag gctgaacgcc tccatcgctg acctgcagag ccagctccgg 6660agccccctgg gcccccgcca tgagacggca cagcagctgg aggtgctgga gcagcagagc 6720acaagcctcg ggcaggacgc acggcggcta ggcggccagg caggagcccc aagacccccc 6780agggccccgg gaggctttca cctgtaccag gcgagccaat tgctggccgg caccgaggcc 6840acactgggcc atgcgaagac gctgttggcg gccatccggg ctgtggaccg caccctgagc 6900gagctcatgt cccagacggg ccacctgggg ctggccaatg cctcggctcc atcaggtgag 6960cagctgctcc ggacactggc cgaggtggag cggctgctct gggagatgcg ggcccgggac 7020ctgggggccc cgcaggcagc agctgaggct gagttggctg cagcacagag attgctggcc 7080cgggtgcagg agcagctgag cagcctctgg gaggagaacc aggcactggc cacacaaacc 7140cgcgaccggc tggcccagca cgaggccggc ctcatggacc tgcgagaggc tttgaaccgg 7200gcagtggacg ccacacggga ggcccaggag ctcaacagcc gcaaccagga gcgcctggag 7260gaagccctgc aaaggaagca ggagctgtcc cgggacaatg ccaccctgca ggccactctg 7320catgcggcta gggacaccct ggccagcgtc ttcagattgc tgcacagcct ggaccaggct 7380aaggaggagc tggagcgcct cgccgccagc ctggatgggg ctcggacccc actgctgcag 7440aggatgcaga ccttctcccc ggcgggcagc aagctgcgtc tagtggaggc cgccgaggcc 7500cacgcacagc agctgggcca gctggcactc aatctgtcca gcatcatcct ggacgtcaac 7560caggaccgcc tcacccagag ggccatcgag gcctccaacg cctacagccg catcctgcag 7620gccgtgcagg ctgccgagga tgctgctggc caggccctgc agcaggcgga ccacacgtgg 7680gcgacggtgg tgcggcaggg cctggtggac cgagcccagc agctcctggc caacagcact 7740gcactagaag aggccatgct ccaggaacag cagaggctgg gccttgtgtg ggctgccctc 7800cagggtgcca ggacccagct ccgagatgtc cgggccaaga aggaccagct ggaggcgcac 7860atccaggcgg cgcaggccat gcttgccatg gacacagacg agacaagcaa gaagatcgca 7920catgccaagg ctgtggctgc tgaagcccag gacaccgcca cccgtgtgca gtcccagctg 7980caggccatgc aggagaatgt ggagcggtgg cagggccagt acgagggcct gcggggccag 8040gacctgggcc aggcagtgct tgacgcaggc cactcagtgt ccaccctgga gaagacgctg 8100ccccagctgc tggccaagct gagcatcctg gagaaccgtg gggtgcacaa cgccagcctg 8160gccctgtccg ccagcattgg ccgcgtgcga gagctcattg cccaggcccg gggggctgcc 8220agtaaggtca aggtgcccat gaagttcaac gggcgctcag gggtgcagct gcgcacccca 8280cgggatcttg ccgaccttgc tgcctacact gccctcaagt tctacctgca gggcccagag 8340cctgagcctg ggcagggtac cgaggatcgc tttgtgatgt acatgggcag ccgccaggcc 8400actggggact acatgggtgt gtctctgcgt gacaagaagg tgcactgggt gtatcagctg 8460ggtgaggcgg gccctgcagt cctaagcatc gatgaggaca ttggggagca gttcgcagct 8520gtcagcctgg acaggactct ccagtttggc cacatgtccg tcacagtgga gagacagatg 8580atccaggaaa ccaagggtga cacggtggcc cctggggcag aggggctgct caacctgcgg 8640ccagacgact tcgtcttcta cgtcgggggg taccccagta ccttcacgcc ccctcccctg 8700cttcgcttcc ccggctaccg gggctgcatc gagatggaca cgctgaatga ggaggtggtc 8760agcctctaca acttcgagag gaccttccag ctggacacgg ctgtggacag gccttgtgcc 8820cgctccaagt cgaccgggga cccgtggctc acggacggct cctacctgga cggcaccggc 8880ttcgcccgca tcagcttcga cagtcagatc agcaccacca agcgcttcga gcaggagctg 8940cggctcgtgt cctacagcgg ggtgctcttc ttcctgaagc agcagagcca gttcctgtgc 9000ttggccgtgc aagaaggcag cctcgtgctg ttgtatgact ttggggctgg cctgaaaaag 9060gccgtcccac tgcagccccc accgcccctg acctcggcca gcaaggcgat ccaggtgttc 9120ctgctggggg gcagccgcaa gcgtgtgctg gtgcgtgtgg agcgggccac ggtgtacagc 9180gtggagcagg acaatgatct ggagctggcc gacgcctact acctgggggg cgtgccgccc 9240gaccagctgc ccccgagcct gcgacggctc ttccccaccg gaggctcagt ccgtggctgc 9300gtcaaaggca tcaaggccct gggcaagtat gtggacctca agcggctgaa cacgacaggc 9360gtgagcgccg gctgcaccgc cgacctgctg gtggggcgcg ccatgacttt ccatggccac 9420ggcttccttc gcctggcgct ctcgaacgtg gcaccgctca ctggcaacgt ctactccggc 9480ttcggcttcc acagcgccca ggacagtgcc ctgctctact accgggcgtc cccggatggg 9540ctatgccagg tgtccctgca gcagggccgt gtgagcctac agctcctgag gactgaagtg 9600aaaactcaag cgggcttcgc cgatggtgcc ccccattacg tcgccttcta cagcaatgcc 9660acgggagtct ggctgtatgt cgatgaccag ctccagcaga tgaagcccca ccggggacca 9720ccccccgagc tccagccgca gcctgagggg cccccgaggc tcctcctggg aggcctgcct 9780gagtctggca ccatttacaa cttcagtggc tgcatcagca acgtcttcgt gcagcggctc 9840ctgggcccac agcgcgtatt tgatctgcag cagaacctgg gcagcgtcaa tgtgagcacg 9900ggctgtgcac ccgccctgca agcccagacc ccgggcctgg ggcctagagg actgcaggcc 9960accgcccgga aggcctcccg ccgcagccgt cagcccgccc ggcatcctgc ctgcatgctg 10020cccccacacc tcaggaccac ccgagactcc taccagtttg ggggttccct gtccagtcac 10080ctggagtttg tgggcatcct ggcccgacat aggaactggc ccagtctctc catgcacgtc 10140ctcccgcgaa gctcccgagg cctcctcctc ttcactgccc gtctgaggcc cggcagcccc 10200tccctggcgc tcttcctgag caatggccac ttcgttgcac agatggaagg cctcgggact 10260cggctccgcg cccagagccg ccagcgctcc cggcctggcc gctggcacaa ggtctccgtg 10320cgctgggaga agaaccggat cctgctggtg acggacgggg cccgggcctg gagccaggag 10380gggccgcacc ggcagcacca gggggcagag cacccccagc cccacaccct ctttgtgggc 10440ggcctcccgg ccagcagcca cagctccaaa cttccggtga ccgtcgggtt cagcggctgt 10500gtgaagagac tgaggctgca cgggaggccc ctgggggccc ccacacggat ggcaggggtc 10560acaccctgca tcttgggccc cctggaggcg ggcctgttct tcccaggcag cgggggagtt 10620atcactttag acctcccagg agctacactg cctgatgtgg gcctggaact ggaggtgcgg 10680cccctggcag tcaccggact gatcttccac ttgggccagg cccggacgcc cccctacttg 10740cagttgcagg tgaccgagaa gcaagtcctg ctgcgggcgg atgacggagc aggggagttc 10800tccacgtcag tgacccgccc ctcagtgctg tgtgatggcc agtggcaccg gctagcggtg 10860atgaaaagcg ggaatgtgct ccggctggag gtggacgcgc agagcaacca caccgtgggc 10920cccttgctgg cggctgcagc tggtgcccca gcccctctgt acctcggggg cctgcctgag 10980cccatggccg tgcagccctg gccccccgcc tactgcggct gcatgaggag gctggcggtg 11040aaccggtccc ccgtcgccat gactcgctct gtggaggtcc acggggcagt gggggccagt 11100ggctgcccag ccgcctag 11118<210> 9<211> 11091<212> DNA<213> 人(Homo sapiens)<400> 9atggcgaagc ggctctgcgc ggggagcgca ctgtgtgttc gcggcccccg gggccccgcg 60ccgctgctgc tggtcgggct ggcgctgctg ggcgcggcgc gggcgcggga ggaggcgggc 120ggcggcttca gcctgcaccc gccctacttc aacctggccg agggcgcccg catcgccgcc 180tccgcgacct gcggagagga ggccccggcg cgcggctccc cgcgccccac cgaggacctt 240tactgcaagc tggtaggggg ccccgtggcc ggcggcgacc ccaaccagac catccggggc 300cagtactgtg acatctgcac ggctgccaac agcaacaagg cacaccccgc gagcaatgcc 360atcgatggca cggagcgctg gtggcagagt ccaccgctgt cccgcggcct ggagtacaac 420gaggtcaacg tcaccctgga cctgggccag gtcttccacg tggcctacgt cctcatcaag 480tttgccaact caccccggcc ggacctctgg gtgctggagc ggtccatgga cttcggccgc 540acctaccagc cctggcagtt ctttgcctcc tccaagaggg actgtctgga gcggttcggg 600ccacagacgc tggagcgcat cacacgggac gacgcggcca tctgcaccac cgagtactca 660cgcatcgtgc ccctggagaa cggagagatc gtggtgtccc tggtgaacgg acgtccgggc 720gccatgaatt tctcctactc gccgctgcta cgtgagttca ccaaggccac caacgtccgc 780ctgcgcttcc tgcgtaccaa cacgctgctg ggccatctca tggggaaggc gctgcgggac 840cccacggtca cccgccggta ttattacagc atcaaggata tcagcatcgg aggccgctgt 900gtctgccacg gccacgcgga tgcctgcgat gccaaagacc ccacggaccc gttcaggctg 960cagtgcacct gccagcacaa cacctgcggg ggcacctgcg accgctgctg ccccggcttc 1020aatcagcagc cgtggaagcc tgcgactgcc aacagtgcca acgagtgcca gtcctgtaac 1080tgctacggcc atgccaccga ctgttactac gaccctgagg tggaccggcg ccgcgccagc 1140cagagcctgg atggcaccta tcagggtggg ggtgtctgta tcgactgcca gcaccacacc 1200accggcgtca actgtgagcg ctgcctgccc ggcttctacc gctctcccaa ccaccctctc 1260gactcgcccc acgtctgccg ccgctgcaac tgcgagtccg acttcacgga tggcacctgc 1320gaggacctga cgggtcgatg ctactgccgg cccaacttct ctggggagcg gtgtgacgtg 1380tgtgccgagg gcttcacggg cttcccaagc tgctacccga cgccctcgtc ctccaatgac 1440accagggagc aggtgctgcc agccggccag attgtgaatt gtgactgcag cgcggcaggg 1500acccagggca acgcctgccg gaaggaccca agggtgggac gctgtctgtg caaacccaac 1560ttccaaggca cccattgtga gctctgcgcg ccagggttct acggccccgg ctgccagccc 1620tgccagtgtt ccagccctgg agtggccgat gaccgctgtg accctgacac aggccagtgc 1680aggtgccgag tgggcttcga gggggccaca tgtgatcgct gtgcccccgg ctactttcac 1740ttccctctct gccagttgtg tggctgcagc cctgcaggaa ccttgcccga gggctgcgat 1800gaggccggcc gctgcctatg ccagcctgag tttgctggac ctcattgtga ccggtgccgc 1860cctggctacc atggtttccc caactgccaa gcatgcacct gcgaccctcg gggagccctg 1920gaccagctct gtggggcggg aggtttgtgc cgctgccgcc ccggctacac aggcactgcc 1980tgccaggaat gcagccccgg ctttcacggc ttccccagct gtgtcccctg ccactgctct 2040gctgaaggct ccctgcacgc agcctgtgac ccccggagtg ggcagtgcag ctgccggccc 2100cgtgtgacgg ggctgcggtg tgacacatgt gtgcccggtg cctacaactt cccctactgc 2160gaagctggct cttgccaccc tgccggtctg gccccagtgg atcctgccct tcctgaggca 2220caggttccct gtatgtgccg ggctcacgtg gaggggccga gctgtgaccg ctgcaaacct 2280gggttctggg gactgagccc cagcaacccc gagggctgta cccgctgcag ctgcgacctc 2340aggggcacac tgggtggagt tgctgagtgc cagccgggca ccggccagtg cttctgcaag 2400ccccacgtgt gcggccaggc ctgcgcgtcc tgcaaggatg gcttctttgg actggatcag 2460gctgactatt ttggctgccg cagctgccgg tgtgacattg gcggtgcact gggccagagc 2520tgtgaaccga ggacgggcgt ctgccggtgc cgccccaaca cccagggccc cacctgcagc 2580gagcctgcga gggaccacta cctcccggac ctgcaccacc tgcgcctgga gctggaggag 2640gctgccacac ctgagggtca cgccgtgcgc tttggcttca accccctcga gttcgagaac 2700ttcagctgga ggggctacgc gcagatggca cctgtccagc ccaggatcgt ggccaggctg 2760aacctgacct cccctgacct tttctggctc gtcttccgat acgtcaaccg gggggccatg 2820agtgtgagcg ggcgggtctc tgtgcgagag gagggcaggt cggccacctg cgccaactgc 2880acagcacaga gtcagcccgt ggccttccca cccagcacgg agcctgcctt catcaccgtg 2940ccccagaggg gcttcggaga gccctttgtg ctgaaccctg gcacctgggc cctgcgtgtg 3000gaggccgaag gggtgctcct ggactacgtg gttctgctgc ctagcgcata ctacgaggcg 3060gcgctcctgc agctgcgggt gactgaggcc tgcacatacc gtccctctgc ccagcagtct 3120ggcgacaact gcctcctcta cacacacctc cccctggatg gcttcccctc ggccgccggg 3180ctggaggccc tgtgtcgcca ggacaacagc ctgccccggc cctgccccac ggagcagctc 3240agcccgtcgc acccgccact gatcacctgc acgggcagtg atgtggacgt ccagcttcaa 3300gtggcagtgc cacagccagg ccgctatgcc ctagtggtgg agtacgccaa tgaggatgcc 3360cgccaggagg tgggcgtggc cgtgcacacc ccacagcggg ccccccagca ggggctgctc 3420tccctgcacc cctgcctgta cagcaccctg tgccggggca ctgcccggga tacccaggac 3480cacctggctg tcttccacct ggactcggag gccagcgtga ggctcacagc cgaacaggca 3540cgcttcttcc tgcacggggt cactctggtg cccattgagg agttcagccc ggagttcgtg 3600gagccccggg tcagctgcat cagcagccac ggcgcctttg gccccaacag tgccgcctgt 3660ctgccctcgc gcttcccaaa gccgccccag cccatcatcc tcagggactg ccaggtgatc 3720ccgctgccgc ccggcctccc gctgacccac gcgcaggatc tcactccagc catgtcccca 3780gctggacccc gacctcggcc ccccaccgct gtggaccctg atgcagagcc caccctgctg 3840cgtgagcccc aggccaccgt ggtcttcacc acccatgtgc ccacgctggg ccgctatgcc 3900ttcctgctgc acggctacca gccagcccac cccaccttcc ccgtggaagt cctcatcaac 3960gccggccgcg tgtggcaggg ccacgccaac gccagcttct gtccacatgg ctacggctgc 4020cgcaccctgg tggtgtgtga gggccaggcc ctgctggacg tgacccacag cgagctcact 4080gtgaccgtgc gtgtgcccaa gggccggtgg ctctggctgg attatgtact cgtggtccct 4140gagaacgtct acagctttgg ctacctccgg gaggagcccc tggataaatc ctatgacttc 4200atcagccact gcgcagccca gggctaccac atcagcccca gcagctcatc cctgttctgc 4260cgaaacgctg ctgcttccct ctccctcttc tataacaacg gagcccgtcc atgtggctgc 4320cacgaagtag gtgctacagg ccccacgtgt gagcccttcg ggggccagtg tccctgccat 4380gcccatgtca ttggccgtga ctgctcccgc tgtgccaccg gatactgggg cttccccaac 4440tgcaggccct gtgactgcgg tgcccgcctc tgtgacgagc tcacgggcca gtgcatctgc 4500ccgccacgca ccatcccgcc cgactgcctg ctgtgccagc cccagacctt tggctgccac 4560cccctggtcg gctgtgagga gtgtaactgc tcagggcccg gcatccagga gctcacagac 4620cctacctgtg acacagacag cggccagtgc aagtgcagac ccaacgtgac tgggcgccgc 4680tgtgatacct gctctccggg cttccatggc tacccccgct gccgcccctg tgactgtcac 4740gaggcgggca ctgcgcctgg cgtgtgtgac cccctcacag ggcagtgcta ctgtaaggag 4800aacgtgcagg gccccaaatg tgaccagtgc agccttggga ccttctcact ggatgctgcc 4860aaccccaaag gttgcacccg ctgcttctgc tttggggcca cggagcgctg ccggagctcg 4920tcctacaccc gccaggagtt cgtggatatg gagggatggg tgctgctgag cactgaccgg 4980caggtggtgc cccacgagcg gcagccaggg acggagatgc tccgtgcaga cctgcggcac 5040gtgcctgagg ctgtgcccga ggctttcccc gagctgtact ggcaggcccc accctcctac 5100ctgggggacc gggtgtcatc ctacggtggg accctccgtt atgaactgca ctcagagacc 5160cagcggggag atgtctttgt ccccatggag agcaggccgg atgtggtgct gcagggcaac 5220cagatgagca tcacattcct ggagccggca taccccacgc ctggccacgt tcaccgtggg 5280cagctgcagc tggtggaggg gaacttccgg catacggaga cgcgcaacac tgtgtcccgc 5340gaggagctca tgatggtgct ggccagcctg gagcagctgc agatccgtgc cctcttctca 5400cagatctcct cggctgtctt cctgcgcagg gtggcactgg aggtggccag cccagcaggc 5460cagggggccc tggccagcaa tgtggagctg tgcctgtgcc ccgccagcta ccggggggac 5520tcatgccagg aatgtgcccc cggcttctat cgggacgtca aaggtctctt cctgggccga 5580tgtgtccctt gtcagtgcca tggacactca gaccgctgcc tccctggctc tggcgtctgt 5640gtggactgcc agcacaacac cgaaggggcc cactgtgagc gctgccaggc tggcttcgtg 5700agcagcaggg acgaccccag cgccccctgt gtcagctgcc cctgccccct ctcagtgcct 5760tccaacaact tcgccgaggg ctgtgtcctg cgaggcggcc gcacccagtg cctctgcaaa 5820cctggttatg caggtgcctc ctgcgagcgg tgtgcgcccg gattctttgg gaacccactg 5880gtgctgggca gctcctgcca gccatgcgac tgcagcggca acggtgaccc caacttgctc 5940ttcagcgact gcgaccccct gacgggcgcc tgccgtggct gcctgcgcca caccactggg 6000ccccgctgcg agatctgtgc ccccggcttc tacggcaacg ccctgctgcc cggcaactgc 6060acccggtgcg actgtacccc atgtgggaca gaggcctgcg acccccacag cgggcactgc 6120ctgtgcaagg cgggcgtgac tgggcggcgc tgtgaccgct gccaggaggg acattttggt 6180ttcgatggct gcgggggctg ccgcccgtgt gcttgtggac cggccgccga gggctccgag 6240tgccaccccc agagcggaca gtgccactgc cgaccaggga ccatgggacc ccagtgccgc 6300gagtgtgccc ctggctactg ggggctccct gagcagggct gcaggcgctg ccagtgccct 6360gggggccgct gtgaccctca cacgggccgc tgcaactgcc ccccggggct cagcggggag 6420cgctgcgaca cctgcagcca gcagcatcag gtgcctgttc caggcgggcc tgtgggccac 6480agcatccact gtgaagtgtg tgaccactgt gtggtcctgc tcctggatga cctggaacgg 6540gccggcgccc tcctccccgc cattcacgag caactgcgtg gcatcaatgc cagctccatg 6600gcctgggccc gtctgcacag gctgaacgcc tccatcgctg acctgcagag ccagctccgg 6660agccccctgg gcccccgcca tgagacggca cagcagctgg aggtgctgga gcagcagagc 6720acaagcctcg ggcaggacgc acggcggcta ggcggccagg cagccgtggg gacccgagac 6780caggcgagcc aattgctggc cggcaccgag gccacactgg gccatgcgaa gacgctgttg 6840gcggccatcc gggctgtgga ccgcaccctg agcgagctca tgtcccagac gggccacctg 6900gggctggcca atgcctcggc tccatcaggt gagcagctgc tccggacact ggccgaggtg 6960gagcggctgc tctgggagat gcgggcccgg gacctggggg ccccgcaggc agcagctgag 7020gctgagttgg ctgcagcaca gagattgctg gcccgggtgc aggagcagct gagcagcctc 7080tgggaggaga accaggcact ggccacacaa acccgcgacc ggctggccca gcacgaggcc 7140ggcctcatgg acctgcgaga ggctttgaac cgggcagtgg acgccacacg ggaggcccag 7200gagctcaaca gccgcaacca ggagcgcctg gaggaagccc tgcaaaggaa gcaggagctg 7260tcccgggaca atgccaccct gcaggccact ctgcatgcgg ctagggacac cctggccagc 7320gtcttcagat tgctgcacag cctggaccag gctaaggagg agctggagcg cctcgccgcc 7380agcctggatg gggctcggac cccactgctg cagaggatgc agaccttctc cccggcgggc 7440agcaagctgc gtctagtgga ggccgccgag gcccacgcac agcagctggg ccagctggca 7500ctcaatctgt ccagcatcat cctggacgtc aaccaggacc gcctcaccca gagggccatc 7560gaggcctcca acgcctacag ccgcatcctg caggccgtgc aggctgccga ggatgctgct 7620ggccaggccc tgcagcaggc ggaccacacg tgggcgacgg tggtgcggca gggcctggtg 7680gaccgagccc agcagctcct ggccaacagc actgcactag aagaggccat gctccaggaa 7740cagcagaggc tgggccttgt gtgggctgcc ctccagggtg ccaggaccca gctccgagat 7800gtccgggcca agaaggacca gctggaggcg cacatccagg cggcgcaggc catgcttgcc 7860atggacacag acgagacaag caagaagatc gcacatgcca aggctgtggc tgctgaagcc 7920caggacaccg ccacccgtgt gcagtcccag ctgcaggcca tgcaggagaa tgtggagcgg 7980tggcagggcc agtacgaggg cctgcggggc caggacctgg gccaggcagt gcttgacgca 8040ggccactcag tgtccaccct ggagaagacg ctgccccagc tgctggccaa gctgagcatc 8100ctggagaacc gtggggtgca caacgccagc ctggccctgt ccgccagcat tggccgcgtg 8160cgagagctca ttgcccaggc ccggggggct gccagtaagg tcaaggtgcc catgaagttc 8220aacgggcgct caggggtgca gctgcgcacc ccacgggatc ttgccgacct tgctgcctac 8280actgccctca agttctacct gcagggccca gagcctgagc ctgggcaggg taccgaggat 8340cgctttgtga tgtacatggg cagccgccag gccactgggg actacatggg tgtgtctctg 8400cgtgacaaga aggtgcactg ggtgtatcag ctgggtgagg cgggccctgc agtcctaagc 8460atcgatgagg acattgggga gcagttcgca gctgtcagcc tggacaggac tctccagttt 8520ggccacatgt ccgtcacagt ggagagacag atgatccagg aaaccaaggg tgacacggtg 8580gcccctgggg cagaggggct gctcaacctg cggccagacg acttcgtctt ctacgtcggg 8640gggtacccca gtaccttcac gccccctccc ctgcttcgct tccccggcta ccggggctgc 8700atcgagatgg acacgctgaa tgaggaggtg gtcagcctct acaacttcga gaggaccttc 8760cagctggaca cggctgtgga caggccttgt gcccgctcca agtcgaccgg ggacccgtgg 8820ctcacggacg gctcctacct ggacggcacc ggcttcgccc gcatcagctt cgacagtcag 8880atcagcacca ccaagcgctt cgagcaggag ctgcggctcg tgtcctacag cggggtgctc 8940ttcttcctga agcagcagag ccagttcctg tgcttggccg tgcaagaagg cagcctcgtg 9000ctgttgtatg actttggggc tggcctgaaa aaggccgtcc cactgcagcc cccaccgccc 9060ctgacctcgg ccagcaaggc gatccaggtg ttcctgctgg ggggcagccg caagcgtgtg 9120ctggtgcgtg tggagcgggc cacggtgtac agcgtggagc aggacaatga tctggagctg 9180gccgacgcct actacctggg gggcgtgccg cccgaccagc tgcccccgag cctgcgacgg 9240ctcttcccca ccggaggctc agtccgtggc tgcgtcaaag gcatcaaggc cctgggcaag 9300tatgtggacc tcaagcggct gaacacgaca ggcgtgagcg ccggctgcac cgccgacctg 9360ctggtggggc gcgccatgac tttccatggc cacggcttcc ttcgcctggc gctctcgaac 9420gtggcaccgc tcactggcaa cgtctactcc ggcttcggct tccacagcgc ccaggacagt 9480gccctgctct actaccgggc gtccccggat gggctatgcc aggtgtccct gcagcagggc 9540cgtgtgagcc tacagctcct gaggactgaa gtgaaaactc aagcgggctt cgccgatggt 9600gccccccatt acgtcgcctt ctacagcaat gccacgggag tctggctgta tgtcgatgac 9660cagctccagc agatgaagcc ccaccgggga ccaccccccg agctccagcc gcagcctgag 9720gggcccccga ggctcctcct gggaggcctg cctgagtctg gcaccattta caacttcagt 9780ggctgcatca gcaacgtctt cgtgcagcgg ctcctgggcc cacagcgcgt atttgatctg 9840cagcagaacc tgggcagcgt caatgtgagc acgggctgtg cacccgccct gcaagcccag 9900accccgggcc tggggcctag aggactgcag gccaccgccc ggaaggcctc ccgccgcagc 9960cgtcagcccg cccggcatcc tgcctgcatg ctgcccccac acctcaggac cacccgagac 10020tcctaccagt ttgggggttc cctgtccagt cacctggagt ttgtgggcat cctggcccga 10080cataggaact ggcccagtct ctccatgcac gtcctcccgc gaagctcccg aggcctcctc 10140ctcttcactg cccgtctgag gcccggcagc ccctccctgg cgctcttcct gagcaatggc 10200cacttcgttg cacagatgga aggcctcggg actcggctcc gcgcccagag ccgccagcgc 10260tcccggcctg gccgctggca caaggtctcc gtgcgctggg agaagaaccg gatcctgctg 10320gtgacggacg gggcccgggc ctggagccag gaggggccgc accggcagca ccagggggca 10380gagcaccccc agccccacac cctctttgtg ggcggcctcc cggccagcag ccacagctcc 10440aaacttccgg tgaccgtcgg gttcagcggc tgtgtgaaga gactgaggct gcacgggagg 10500cccctggggg cccccacacg gatggcaggg gtcacaccct gcatcttggg ccccctggag 10560gcgggcctgt tcttcccagg cagcggggga gttatcactt tagacctccc aggagctaca 10620ctgcctgatg tgggcctgga actggaggtg cggcccctgg cagtcaccgg actgatcttc 10680cacttgggcc aggcccggac gcccccctac ttgcagttgc aggtgaccga gaagcaagtc 10740ctgctgcggg cggatgacgg agcaggggag ttctccacgt cagtgacccg cccctcagtg 10800ctgtgtgatg gccagtggca ccggctagcg gtgatgaaaa gcgggaatgt gctccggctg 10860gaggtggacg cgcagagcaa ccacaccgtg ggccccttgc tggcggctgc agctggtgcc 10920ccagcccctc tgtacctcgg gggcctgcct gagcccatgg ccgtgcagcc ctggcccccc 10980gcctactgcg gctgcatgag gaggctggcg gtgaaccggt cccccgtcgc catgactcgc 11040tctgtggagg tccacggggc agtgggggcc agtggctgcc cagccgccta g 11091<210> 10<211> 1014<212> DNA<213> 人(Homo sapiens)<400> 10atgacaaaca acagcggctc caaagccgaa ctcgttgtgg gagggaaata caaactggtg 60cggaagatcg ggtctggctc ctttggagac gtttatctgg gcatcaccac caccaacggc 120gaggacgtag cagtgaagct ggaatctcag aaggtcaagc acccccagtt gctgtatgag 180agcaaactct acacgattct tcaaggtggg gttggcatcc cccacatgca ctggtatggt 240caggaaaaag acaacaatgt gctagtcatg gaccttctgg gacccagcct cgaagacctc 300tttaatttct gttcaagaag gttcaccatg aaaactgtac ttatgttagc cgaccagatg 360atcagcagaa ttgaatacgt gcatacaaag aattttctac accgagacat taaaccagat 420aacttcctga tgggtactgg gcgtcactgt aataagttgt tccttattga ttttggtttg 480gccaaaaagt acagagacaa caggaccagg caacacatac cgtacagaga agataaacac 540ctcattggca ctgtccgata tgccagcatc aatgcacatc ttggtattga gcagagccgc 600cgagatgaca tggaatcctt aggctacgtt ttcatgtatt ttaatagaac cagcctgccg 660tggcaaggac taagggctat gacaaaaaaa caaaaatatg aaaagattag tgagaagaag 720atgtccaccc ctgttgaagt tttatgtaag gggtttcctg cagaattcgc catgtacttg 780aactactgtc gtgggctgcg ctttgaggaa gtcccagatt acatgtatct gaggcagcta 840ttccgcattc ttttcaggac cctgaaccac caatatgact acacatttga ttggacgatg 900ttaaagcaga aagcagcaca gcaggcagcc tcttccagtg ggcagggtca gcaggcccaa 960acccagacag gcaagcaaac tgaaaaaaac aagaataatg tgaaagataa ctaa 1014<210> 11<211> 2667<212> DNA<213> 人(Homo sapiens)<400> 11atggagtcgc tcctgctgcc ggtgctgctg ctgctggcca tactgtggac gcaggctgcc 60gccctcatta atctcaagta ctcggtagaa gaggagcagc gcgccgggac ggtgattgcc 120aacgtggcca aagacgcgcg agaggcgggc ttcgcgctgg acccccggca ggcttcagcc 180tttcgcgtgg tgtccaactc ggctccacac ctagtggaca tcaatcccag ctctggcctg 240ctggtcacca agcagaagat tgaccgtgat ctgctgtgcc gccagagccc caagtgcatc 300atctcgctcg aggtcatgtc cagctcaatg gaaatctgcg tgataaaggt ggagatcaag 360gacctgaacg acaatgcgcc cagtttcccg gcagcacaga tcgagctgga gatctcggag 420gcagccagcc ctggcacgcg catcccgctg gacagcgctt acgatccaga ctcaggaagc 480tttggcgtgc agacttacga gctcacgccc aacgagctgt tcggcctgga gatcaagacg 540cgcggcgacg gctcccgctt tgccgaactc gtggtggaaa agagcctgga ccgcgagacg 600cagtcgcact acagcttccg aatcactgcg ctagacggtg gcgacccgcc gcgcctgggc 660accgttggcc ttagtatcaa ggtgaccgac tccaatgaca acaacccggt gtttagcgag 720tccacctacg cggtgagcgt gccagaaaac tcgcctccca acacacccgt catccgcctc 780aacgccagcg atccagacga gggcaccaac ggccaggtgg tctactcctt ctatggctac 840gtcaacgacc gcacgcgcga gctctttcag atcgacccgc acagtggcct ggtcactgtc 900actggcgctt tagactacga agaggggcac gtgtacgaac tggacgtgca ggctaaggac 960ttggggccca attccatccc ggcacactgc aaggtcaccg tcagcgtgct ggacaccaat 1020gacaatccgc cggtcatcaa cctgctgtca gtcaacagtg agcttgtgga ggtcagcgag 1080agcgcccccc cgggctacgt gatcgccttg gtgcgggtgt ctgatcgcga ctcaggcctc 1140aatggacgtg tgcagtgccg tttgctgggc aatgtgccct ttcgactgca ggaatatgag 1200agcttctcca ctattctggt ggacggacgg ctggaccgcg agcagcacga ccaatacaac 1260ctcacaattc aggcacgcga cggcggcgtg cccatgctgc agagtgccaa gtcctttacc 1320gtgctcatca ctgacgaaaa tgacaaccac ccgcactttt ccaagcccta ctaccaggtc 1380attgtgcagg agaacaacac gcctggcgcc tatctgctct ctgtgtctgc tcgcgacccc 1440gacctgggtc tcaacggcag tgtctcctac cagatcgtgc cgtcgcaggt gcgggacatg 1500cctgtcttca cctatgtctc catcaatccc aactcaggcg acatctacgc gctgcgatcc 1560tttaaccacg agcagaccaa ggcgttcgaa ttcaaggtgc tggccaagga cggcggcctt 1620ccctcactgc aaagcaacgc tacggtgcgg gtcatcatcc tcgacgtcaa cgacaacacc 1680ccggtcatca cagccccacc tctgattaac ggcactgccg aggtctacat accccgcaac 1740tctggcatag gctacctggt gactgttgtc aaggcagaag actacgatga gggcgaaaat 1800ggccgagtca cctacgacat gaccgagggc gaccgcggct tctttgaaat agaccaggtc 1860aatggcgaag tcagaaccac ccgcaccttc ggggagagct ccaagtcctc ctatgagctt 1920atcgtggtgg ctcacgacca cggcaagaca tctctctctg cctctgctct cgtcctaatc 1980tacttgtccc ctgctctcga tgcccaagag tcaatgggct ctgtgaactt gtccttgatt 2040ttcattattg ccctgggctc cattgcgggc atcctctttg taactatgat cttcgtggca 2100atcaagtgca agcgagacaa caaagagatc cggacctaca actgcagtaa ttgtttaacc 2160atcacttgtc tcctcggctg ttttataaaa ggacaaaaca gcaagtgtct gcattgcatc 2220tcggtttctc ccattagcga ggagcaagac aaaaagacag aggagaaagt gagcctaagg 2280ggaaagagaa ttgctgagta ctcctatggg catcaaaaga aatcaagcaa gaagaaaaaa 2340atcagtaaga atgacatccg cctggtaccc cgggatgtgg aggagacaga caagatgaac 2400gttgtcagtt gctcttccct gacctcctcc ctcaactatt ttgactacca ccagcagacg 2460ctgcccctgg gctgccgccg ctctgagagc actttcctga atgtggagaa ccagaatacc 2520cgcaacacca gtgctaacca catctaccat cactctttca acagccaggg gccccagcag 2580cctgacctga ttatcaacgg tgtgcctctg cctgaggtga gtgcagctaa gtggctctgt 2640gaggttctcc caggtctcct tctttag 2667<210> 12<211> 2568<212> DNA<213> 人(Homo sapiens)<400> 12atggagtcgc tcctgctgcc ggtgctgctg ctgctggcca tactgtggac gcaggctgcc 60gccctcatta atctcaagta ctcggtagaa gaggagcagc gcgccgggac ggtgattgcc 120aacgtggcca aagacgcgcg agaggcgggc ttcgcgctgg acccccggca ggcttcagcc 180tttcgcgtgg tgtccaactc ggctccacac ctagtggaca tcaatcccag ctctggcctg 240ctggtcacca agcagaagat tgaccgtgat ctgctgtgcc gccagagccc caagtgcatc 300atctcgctcg aggtcatgtc cagctcaatg gaaatctgcg tgataaaggt ggagatcaag 360gacctgaacg acaatgcgcc cagtttcccg gcagcacaga tcgagctgga gatctcggag 420gcagccagcc ctggcacgcg catcccgctg gacagcgctt acgatccaga ctcaggaagc 480tttggcgtgc agacttacga gctcacgccc aacgagctgt tcggcctgga gatcaagacg 540cgcggcgacg gctcccgctt tgccgaactc gtggtggaaa agagcctgga ccgcgagacg 600cagtcgcact acagcttccg aatcactgcg ctagacggtg gcgacccgcc gcgcctgggc 660accgttggcc ttagtatcaa ggtgaccgac tccaatgaca acaacccggt gtttagcgag 720tccacctacg cggtgagcgt gccagaaaac tcgcctccca acacacccgt catccgcctc 780aacgccagcg atccagacga gggcaccaac ggccaggtgg tctactcctt ctatggctac 840gtcaacgacc gcacgcgcga gctctttcag atcgacccgc acagtggcct ggtcactgtc 900actggcgctt tagactacga agaggggcac gtgtacgaac tggacgtgca ggctaaggac 960ttggggccca attccatccc ggcacactgc aaggtcaccg tcagcgtgct ggacaccaat 1020gacaatccgc cggtcatcaa cctgctgtca gtcaacagtg agcttgtgga ggtcagcgag 1080agcgcccccc cgggctacgt gatcgccttg gtgcgggtgt ctgatcgcga ctcaggcctc 1140aatggacgtg tgcagtgccg tttgctgggc aatgtgccct ttcgactgca ggaatatgag 1200agcttctcca ctattctggt ggacggacgg ctggaccgcg agcagcacga ccaatacaac 1260ctcacaattc aggcacgcga cggcggcgtg cccatgctgc agagtgccaa gtcctttacc 1320gtgctcatca ctgacgaaaa tgacaaccac ccgcactttt ccaagcccta ctaccaggtc 1380attgtgcagg agaacaacac gcctggcgcc tatctgctct ctgtgtctgc tcgcgacccc 1440gacctgggtc tcaacggcag tgtctcctac cagatcgtgc cgtcgcaggt gcgggacatg 1500cctgtcttca cctatgtctc catcaatccc aactcaggcg acatctacgc gctgcgatcc 1560tttaaccacg agcagaccaa ggcgttcgaa ttcaaggtgc tggccaagga cggcggcctt 1620ccctcactgc aaagcaacgc tacggtgcgg gtcatcatcc tcgacgtcaa cgacaacacc 1680ccggtcatca cagccccacc tctgattaac ggcactgccg aggtctacat accccgcaac 1740tctggcatag gctacctggt gactgttgtc aaggcagaag actacgatga gggcgaaaat 1800ggccgagtca cctacgacat gaccgagggc gaccgcggct tctttgaaat agaccaggtc 1860aatggcgaag tcagaaccac ccgcaccttc ggggagagct ccaagtcctc ctatgagctt 1920atcgtggtgg ctcacgacca cggcaagaca tctctctctg cctctgctct cgtcctaatc 1980tacttgtccc ctgctctcga tgcccaagag tcaatgggct ctgtgaactt gtccttgatt 2040ttcattattg ccctgggctc cattgcgggc atcctctttg taactatgat cttcgtggca 2100atcaagtgca agcgagacaa caaagagatc cggacctaca actgcagaat tgctgagtac 2160tcctatgggc atcaaaagaa atcaagcaag aagaaaaaaa tcagtaagaa tgacatccgc 2220ctggtacccc gggatgtgga ggagacagac aagatgaacg ttgtcagttg ctcttccctg 2280acctcctccc tcaactattt tgactaccac cagcagacgc tgcccctggg ctgccgccgc 2340tctgagagca ctttcctgaa tgtggagaac cagaataccc gcaacaccag tgctaaccac 2400atctaccatc actctttcaa cagccagggg ccccagcagc ctgacctgat tatcaacggt 2460gtgcctctgc ctgagactga aaactattct tttgactcca actacgtgaa tagccgagcc 2520catttaatca agaggtatgt tggtttgctt gcttattgct gcaactaa 2568<210> 13<211> 990<212> DNA<213> 人(Homo sapiens)<400> 13atggtgacga aggcctttgt cttgttggcc atctttgcag aagcctctgc aaaatcgtgt 60gctccaaata aagcagatgt cattcttgtg ttttgctatc ccaaaaccat catcaccaaa 120atccccgagt gtccctatgg atgggaagtt catcagctgg ccctcggagg gctgtgttac 180aatggggtcc acgaaggagg ttactaccaa tttgtgatcc cagatttatc acctaaaaac 240aagtcctatt gtggaaccca gtctgagtac aagccaccta tctatcactt ctacagtcac 300atcgtttcca atgacaccac agtgattgta aaaaaccagc ctgtcaacta ctccttctcc 360tgcacctacc actccaccta cttggtgaac caggctgcct ttgaccagag agtggccact 420gttcacgtga agaacgggag catgggcaca tttgagagcc aactgtctct caacttctac 480actaatgcca agttctccat caagaaagaa gctccctttg tcctggaggc atccgaaatc 540ggttcagatc tgtttgcagg agtggaagcc aaagggttaa gcattaggtt taaagtggtc 600ttgaacagct gttgggccac cccctcggct gacttcatgt atcccttgca gtggcagctg 660atcaacaagg gctgccccac ggatgaaacc gtcctcgtgc atgagaatgg gagagatcac 720agggcaacct tccaattcaa tgctttccgg ttccagaaca tccccaaact ctccaaggtg 780tggttacact gtgagacgtt catctgcgac agtgagaaac tctcctgccc agtgacctgc 840gataaacgga agcgcctcct gcgagaccag accgggggag tcctggtcgt ggagctctcc 900ctgcggagca ggggattttc cagtctctat agcttctcag atgttctcca ccacctcatc 960atgatgttgg ggatttgtgc cgtgttatag 990<210> 14<211> 699<212> DNA<213> 人(Homo sapiens)<400> 14atgctctaca caaggaaaaa cctgacctgc gcacaaacca tcaactcctc agcttttggg 60aacttgaatg tgaccaagaa aaccaccttc attgtccatg gattcaggcc aacaggctcc 120cctcctgttt ggatggatga cttagtaaag ggtttgctct ctgttgaaga catgaacgta 180gttgttgttg attggaatcg aggagctaca actttaatat atacccatgc ctctagtaag 240accagaaaag tagccatggt cttgaaggaa tttattgacc agatgttggc agaaggagct 300tctcttgatg acatttacat gatcggagta agtctaggag cccacatatc tgggtttgtt 360ggagagatgt acgatggatg gctggggaga attacaggcc tcgaccctgc aggcccttta 420ttcaacggga aacctcacca agacagatta gatcccagtg atgcgcagtt tgttgatgtc 480atccattccg acactgatgg taacgctcct ttccttgtgg cactgggcta caaggagcca 540ttaggaaaca tagacttcta cccaaatgga ggattggatc aacctggctg ccccaaaaca 600atattgggag gaaatgttaa ggaaatgata caggcttcct atatcttttt ccttaaaaac 660gactctatgg acttaagttc accgaaggaa gtggaatga699<210> 15<211> 1359<212> DNA<213> 人(Homo sapiens)<400> 15atgttgagat tctacttatt catcagtttg ttgtgcttgt caagatcaga cgcagaagaa 60acatgtcctt cattcaccag gctgagcttt cacagtgcag tggttggtac gggactaaat 120gtgaggctga tgctctacac aaggaaaaac ctgacctgcg cacaaaccat caactcctca 180gcttttggga acttgaatgt gaccaagaaa accaccttca ttgtccatgg attcaggcca 240acaggctccc ctcctgtttg gatggatgac ttagtaaagg gtttgctctc tgttgaagac 300atgaacgtag ttgttgttga ttggaatcga ggagctacaa ctttaatata tacccatgcc 360tctagtaaga ccagaaaagt agccatggtc ttgaaggaat ttattgacca gatgttggca 420gaaggagctt ctcttgatga catttacatg atcggagtaa gtctaggagc ccacatatct 480gggtttgttg gagagatgta cgatggatgg ctggggagaa ttacaggcct cgaccctgca 540ggccctttat tcaacgggaa acctcaccaa gacagattag atcccagtga tgcgcagttt 600gttgatgtca tccattccga cactgatgca ctgggctaca aggagccatt aggaaacata 660gacttctacc caaatggagg attggatcaa cctggctgcc ccaaaacaat attgggagga 720tttcagtatt ttaaatgtga ccaccagagg tctgtatacc tgtacctgtc ttccctgaga 780gagagctgca ccatcactgc gtatccctgt gactcctacc aggattatag gaatggcaag 840tgtgtcagct gcggcacgtc acaaaaagag tcctgtcccc ttctgggcta ttatgctgat 900aattggaaag accatctaag ggggaaagat cctccaatga cgaaggcatt ctttgacaca 960gctgaggaga gcccattctg catgtatcat tactttgtgg atattataac atgggacaag 1020aatgtaagaa gaggggacat taccatcaaa ttgagagaca aagctggaaa cacccacaga 1080tccaaaatca tcagtaatga acccaccaca tttcagaaat atcaccaagt gagtctactt 1140gcaagattta atcaagatct ggataaagtg gctgcaattt ccttgatgtt ctctacagga 1200tctctaatag gcccaaggta caagctcagg attctccgaa tgaagttaag gtcccttgcc 1260catccggaga ggcctcagct gtgtcggtat gatcttgtcc tgatggaaaa cgttgaaaca 1320gtcttccaac ctattctttg cccagagttg cagttgtaa1359<210> 16<211> 1353<212> DNA<213> 人(Homo sapiens)<400> 16atggggctcc ggagccacca cctcagcctg ggccttctgc ttctgtttct actccctgca 60gagtgcctgg gagctgaggg ccggctggct ctcaagctgt tccgtgacct ctttgccaac 120tacacaagtg ccctgagacc tgtggcagac acagaccaga ctctgaatgt gaccctggag 180gtgacactgt cccagatcat cgacatggat gaacggaacc aggtgctgac cctgtatctg 240tggatacggc aggagtggac agatgcctac ctacgatggg accccaatgc ctatggtggc 300ctggatgcca tccgcatccc cagcagtctt gtgtggcggc cagacatcgt actctataac 360aaagccgacg cgcagcctcc aggttccgcc agcaccaacg tggtcctgcg ccacgatggc 420gccgtgcgct gggacgcgcc ggccatcacg cgcagctcgt gccgcgtgga tgtagcagcc 480ttcccgttcg acgcccagca ctgcggcctg acgttcggct cctggactca cggcgggcac 540caactggatg tgcggccgcg cggcgctgca gccagcctgg cggacttcgt ggagaacgtg 600gagtggcgcg tgctgggcat gccggcgcgg cggcgcgtgc tcacctacgg ctgctgctcc 660gagccctacc ccgacgtcac cttcacgctg ctgctgcgcc gccgcgccgc cgcctacgtg 720tgcaacctgc tgctgccctg cgtgctcatc tcgctgcttg cgccgctcgc cttccacctg 780cctgccgact caggcgagaa ggtgtcgctg ggcgtcaccg tgctgctggc gctcaccgtc 840ttccagttgc tgctggccga gagcatgcca ccggccgaga gcgtgccgct catcgggaag 900tactacatgg ccactatgac catggtcaca ttctcaacag cactcaccat ccttatcatg 960aacctgcatt actgtggtcc cagtgtccgc ccagtgccag cctgggctag ggccctcctg 1020ctgggacacc tggcacgggg cctgtgcgtg cgggaaagag gggagccctg tgggcagtcc 1080aggccacctg agttatctcc tagcccccag tcgcctgaag gaggggctgg ccccccagcg 1140ggcccttgcc acgagccacg atgtctgtgc cgccaggaag ccctactgca ccacgtagcc 1200accattgcca ataccttccg cagccaccga gctgcccagc gctgccatga ggactggaag 1260cgcctggccc gtgtgatgga ccgcttcttc ctggccatct tcttctccat ggccctggtc 1320atgagcctcc tggtgctggt gcaggccctg tga 1353<210> 17<211> 768<212> DNA<213> 人(Homo sapiens)<400> 17atggttaagg gtgagaaagg ccccaagggc aagaagatca ccctcaaggt ggccaggaat 60tgcatcaaaa tcacttttga tgggaaaaag cgccttgact tgagcaagat gggaattacc 120accttcccca agtgtattct gcgccttagt gacatggacg agctggacct tagccggaat 180cttatcagga agatccctga ctccatctcc aagttccaga acctccggtg gctggacctg 240cacagcaact acatagacaa gctgcctgag tccattggcc agatgaccag cctgctctac 300ctcaacgtca gcaacaaccg gctgaccagc aacgggctgc ccgtggagct gaagcaactc 360aagaacatcc gcgctgtgaa cctaggcttg aaccacctgg acagcgtgcc caccacactg 420ggggccctga aggagctcca cgaggtaggg ctccatgaca acctactgaa caacatcccc 480gtgagcatct ccaagctccc caagctgaaa aagctcaaca taaagcggaa cccctttcca 540aagccaggtg agtcggaaat attcatagac tccatcagga ggctggagaa cttgtatgtt 600gtggaggaga aggatctgtg tgcggcttgc ctgagaaaat gccaaaacgc ccgggacaac 660ctgaatagaa tcaagaacat ggccacgacg acaccgagaa agaccatctt tcccaatctg 720atctcaccca attccatggc caaggactcc tgggaagact ggaggtga 768<210> 18<211> 645<212> DNA<213> 人(Homo sapiens)<400> 18atgcaggcag gaactcagtc aacgcatgag tctctgaagc ctcagagggt acaatttcag 60tcccgaaatt ttcacaacat tttgcaatgg cagcctggga gggcacttac tggcaacagc 120agtgtctatt ttgtgcagta caaaatatat ggacagagac aatggaaaaa taaagaagac 180tgttggggta ctcaagaact ctcttgtgac cttaccagtg aaacctcaga catacaggaa 240ccttattacg ggagggtgag ggcggcctcg gctgggagct actcagaatg gagcatgacg 300ccgcggttca ctccctggtg ggaaacaaaa atagatcctc cagtcatgaa tataacccaa 360gtcaatggct ctttgttggt aattctccat gctccaaatt taccatatag ataccaaaag 420gaaaaaaatg tatctataga agattactat gaactactat accgagtttt tataattaac 480aattcactag aaaaggagca aaaggtttat gaaggggctc acagagcggt tgaaattgaa 540gctctaacac cacactccag ctactgtgta gtggctgaaa tatatcagcc catgttagac 600agaagaagtc agagaagtga agagagatgt gtggaaattc catga 645<210> 19<211> 696<212> DNA<213> 人(Homo sapiens)<400> 19atgatgccta aacattgctt tctaggcttc ctcatcagtt tcttccttac tggtgtagca 60ggaactcagt caacgcatga gtctctgaag cctcagaggg tacaatttca gtcccgaaat 120tttcacaaca ttttgcaatg gcagcctggg agggcactta ctggcaacag cagtgtctat 180tttgtgcagt acaaaatata tggacagaga caatggaaaa ataaagaaga ctgttggggt 240actcaagaac tctcttgtga ccttaccagt gaaacctcag acatacagga accttattac 300gggagggtga gggcggcctc ggctgggagc tactcagaat ggagcatgac gccgcggttc 360actccctggt gggaaacaaa aatagatcct ccagtcatga atataaccca agtcaatggc 420tctttgttgg taattctcca tgctccaaat ttaccatata gataccaaaa ggaaaaaaat 480gtatctatag aagattacta tgaactacta taccgagttt ttataattaa caattcacta 540gaaaaggagc aaaaggttta tgaaggggct cacagagcgg ttgaaattga agctctaaca 600ccacactcca gctactgtgt agtggctgaa atatatcagc ccatgttaga cagaagaagt 660cagagaagtg aagagagatg tgtggaaatt ccatga 696<210> 20<211> 792<212> DNA<213> 人(Homo sapiens)<400> 20atgatgccta aacattgctt tctaggcttc ctcatcagtt tcttccttac tggtgtagca 60ggaactcagt caacgcatga gtctctgaag cctcagaggg tacaatttca gtcccgaaat 120tttcacaaca ttttgcaatg gcagcctggg agggcactta ctggcaacag cagtgtctat 180tttgtgcagt acaaaatcat gttctcatgc agcatgaaaa gctctcacca gaagccaagt 240ggatgctggc agcacatttc ttgtaacttc ccaggctgca gaacattggc taaatatgga 300cagagacaat ggaaaaataa agaagactgt tggggtactc aagaactctc ttgtgacctt 360accagtgaaa cctcagacat acaggaacct tattacggga gggtgagggc ggcctcggct 420gggagctact cagaatggag catgacgccg cggttcactc cctggtggga aacaaaaata 480gatcctccag tcatgaatat aacccaagtc aatggctctt tgttggtaat tctccatgct 540ccaaatttac catatagata ccaaaaggaa aaaaatgtat ctatagaaga ttactatgaa 600ctactatacc gagtttttat aattaacaat tcactagaaa aggagcaaaa ggtttatgaa 660ggggctcaca gagcggttga aattgaagct ctaacaccac actccagcta ctgtgtagtg 720gctgaaatat atcagcccat gttagacaga agaagtcaga gaagtgaaga gagatgtgtg 780gaaattccat ga 792<210> 21<211> 780<212> DNA<213> 人(Homo sapiens)<400> 21atgtatgtat tatctccagt ggaatttata attctacaac ttttatttat tcaggccatt 60tccagcagtt taaaaggttt cctttcagct atgagactgg ctcatagagg ctgtaatgtt 120gatacaccag tttcaacgct cacaccagtg aagacttcag aatttgaaaa ctttaaaact 180aaaatggtta tcacatccaa aaaagactat cctctaagta agaattttcc atattccttg 240gaacatcttc agacttctta ctgtgggctt gtccgagttg atatgcgtat gctttgctta 300aaaagcctta ggaaattaga cttgagtcac aaccatataa aaaagcttcc agctacaatt 360ggagacctca tacaccttca agaacttaac ctgaatgaca atcacttgga gtcatttagt 420gtagccttgt gtcattctac actccagaag tcacttcgga gtttggacct cagcaagaac 480aaaatcaagg cactccctgt gcagttttgc cagctccagg aacttaagaa tttaaaactt 540gacgataatg aattgattca atttccttgc aagataggac aactaataaa ccttcgcttt 600ttgtcagcag ctcgaaataa gcttccattt ttgcctagtg aatttagaaa tttatccctt 660gaatacttgg atctttttgg aaatactttt gaacaaccaa aagtccttcc agtaataaag 720ctgcaagcac cattaacttt attggaatct tctgcacgaa ccatattaca taataggtaa 780<210> 22<211> 1251<212> DNA<213> 人(Homo sapiens)<400> 22atgaagctac actgtgaggt ggaggtgatc agccggcact tgcccgcctt ggggcttagg 60aaccggggca agggcgtccg agccgtgttg agcctctgtc agcagacttc caggagtcag 120ccgccggtcc gagccttcct gctcatctcc accctgaagg acaagcgcgg gacccgctat 180gagctaaggg agaacattga gcaattcttc accaaatttg tagatgaggg gaaagccact 240gttcggttaa aggagcctcc tgtggatatc tgtctaagta aggccatttc cagcagttta 300aaaggtttcc tttcagctat gagactggct catagaggct gtaatgttga tacaccagtt 360tcaacgctca caccagtgaa gacttcagaa tttgaaaact ttaaaactaa aatggttatc 420acatccaaaa aagactatcc tctaagtaag aattttccat attccttgga acatcttcag 480acttcttact gtgggcttgt ccgagttgat atgcgtatgc tttgcttaaa aagccttagg 540aaattagact tgagtcacaa ccatataaaa aagcttccag ctacaattgg agacctcata 600caccttcaag aacttaacct gaatgacaat cacttggagt catttagtgt agccttgtgt 660cattctacac tccagaagtc acttcggagt ttggacctca gcaagaacaa aatcaaggca 720ctccctgtgc agttttgcca gctccaggaa cttaagaatt taaaacttga cgataatgaa 780ttgattcaat ttccttgcaa gataggacaa ctaataaacc ttcgcttttt gtcagcagct 840cgaaataagc ttccattttt gcctagtgaa tttagaaatt tatcccttga atacttggat 900ctttttggaa atacttttga acaaccaaaa gtccttccag taataaagct gcaagcacca 960ttaactttat tggaatcttc tgcacgaacc atattacata ataggaatag gattccatat 1020ggctctcata tcattccatt ccatctctgc caagatttgg ataccgcaaa aatttgtgtt 1080tgtggaagat tctgtctgaa ctctttcatt caaggaacta ctaccatgaa tctgcattct 1140gttgcccaca ctgtggtctt agtagataat ttgggtggta ctgaagcacc tattatctct 1200tatttctgtt ctctaggctg ttatgttaat tcctctgata tgttaaagta a 1251<210> 23<211> 461<212> PRT<213> 人(Homo sapiens)<400> 23Met Leu Gly Ile Trp Ile Val Ala Phe Leu Phe Phe Gly Thr Ser Arg1 5 10 15Gly Lys Glu Val Cys Tyr Glu Arg Leu Gly Cys Phe Lys Asp Gly Leu20 25 30Pro Trp Thr Arg Thr Phe Ser Thr Glu Leu Val Gly Leu Pro Trp Ser35 40 45Pro Glu Lys Ile Asn Thr Arg Phe Leu Leu Tyr Thr Ile His Asn Pro50 55 60Asn Ala Tyr Gln Glu Ile Ser Ala Val Asn Ser Ser Thr Ile Gln Ala65 70 75 80Ser Tyr Phe Gly Thr Asp Lys Ile Thr Arg Ile Asn Ile Ala Gly Trp85 90 95Lys Thr Asp Gly Lys Trp Gln Arg Asp Met Cys Asn Val Leu Leu Gln100 105 110Leu Glu Asp Ile Asn Cys Ile Asn Leu Asp Trp Ile Asn Gly Ser Arg115 120 125Glu Tyr Ile His Ala Val Asn Asn Leu Arg Val Val Gly Ala Glu Val130 135 140Ala Tyr Phe Ile Asp Val Leu Met Lys Lys Phe Glu Tyr Ser Pro Ser145 150 155 160Lys Val His Leu Ile Gly His Ser Leu Gly Ala His Leu Ala Gly Glu165 170 175Ala Gly Ser Arg Ile Pro Gly Leu Gly Arg Ile Thr Gly Leu Asp Pro180 185 190Ala Gly Pro Phe Phe His Asn Thr Pro Lys Glu Val Arg Leu Asp Pro195 200 205Ser Asp Ala Asn Phe Val Asp Val Ile His Thr Asn Ala Ala Arg Ile210 215 220Leu Phe Glu Leu Gly Val Gly Thr Ile Asp Ala Cys Gly His Leu Asp225 230 235 240Phe Tyr Pro Asn Gly Gly Lys His Met Pro Gly Cys Glu Asp Leu Ile245 250 255Thr Pro Leu Leu Lys Phe Asn Phe Asn Ala Tyr Lys Lys Glu Met Ala260 265 270Ser Phe Phe Asp Cys Asn His Ala Arg Ser Tyr Gln Phe Tyr Ala Glu275 280 285Ser Ile Leu Asn Pro Asp Ala Phe Ile Ala Tyr Pro Cys Arg Ser Tyr290 295 300Thr Ser Phe Lys Ala Gly Thr Cys Val Gly Cys Ala Asp Leu Leu His305 310 315 320Arg Ile Asp Lys Ile Gly Ser His Thr Ser His Val Phe Leu Thr Leu325 330 335Ser Leu Pro Phe Leu Leu Val Ser Leu Tyr Leu Gly Trp Arg His Lys340 345 350Leu Ser Val Lys Leu Ser Gly Ser Glu Val Thr Gln Gly Thr Val Phe355 360 365Leu Arg Val Gly Gly Ala Val Arg Lys Thr Gly Glu Phe Ala Ile Val370 375 380Ser Gly Lys Leu Glu Pro Gly Met Thr Tyr Thr Lys Leu Ile Asp Ala385 390 395 400Asp Val Asn Val Gly Asn Ile Thr Ser Val Gln Phe Ile Trp Lys Lys405 410 415His Leu Phe Glu Asp Ser Gln Asn Lys Leu Gly Ala Glu Met Val Ile420 425 430Asn Thr Ser Gly Lys Tyr Gly Tyr Lys Ser Thr Phe Cys Ser Gln Asp435 440 445Ile Met Gly Pro Asn Ile Leu Gln Asn Leu Lys Pro Cys450 455 460<210> 24<211> 308<212> PRT<213> 人(Homo sapiens)<400> 24Met Pro Phe Leu Gln Leu Lys Gly Arg Ala Thr Pro Pro Ser Trp Arg1 5 10 15His Asp Ser Arg Ser Leu Val His Leu Leu Asp Gly Lys Glu Gly Val20 25 30Trp Asp Thr Thr Gly Tyr Ala Leu Gly Ser Arg Glu Ser Leu Asn Pro35 40 45Asp Met Gly Ile Gly Asp Pro His Gly His Ser Thr Val His Thr Arg50 55 60Glu Ala Gly Thr Ala Cys Pro Leu Gln Leu Leu Gly Ala Arg Glu Ala65 70 75 80Ser Leu Leu Ala Cys Gly Ile Cys Gln Ala Ser Gly Gln Ile Phe Ile85 90 95Thr Gln Thr Leu Gly Ile Lys Gly Tyr Arg Thr Val Val Ala Leu Asp100 105 110Lys Val Pro Glu Asp Val Gln Glu Tyr Ser Trp Tyr Trp Gly Ala Asn115 120 125Asp Ser Ala Gly Asn Met Ile Ile Ser His Lys Pro Pro Ser Ala Gln130 135 140Gln Pro Gly Pro Met Tyr Thr Gly Arg Glu Arg Val Asn Arg Glu Gly145 150 155 160Ser Leu Leu Ile Arg Pro Thr Ala Leu Asn Asp Thr Gly Asn Tyr Thr
165 170 175Val Arg Val Val Ala Gly Asn Glu Thr Gln Arg Ala Thr Gly Trp Leu180 185 190Glu Val Leu Asp Gly Pro Asp Tyr Val Leu Leu Arg Ser Asn Pro Asp195 200 205Asp Phe Asn Gly Ile Val Thr Ala Glu Ile Gly Ser Gln Val Glu Met210 215 220Glu Cys Ile Cys Tyr Ser Phe Leu Asp Leu Lys Tyr His Trp Ile His225 230 235 240Asn Gly Ser Leu Leu Asn Phe Ser Asp Ala Lys Met Asn Leu Ser Ser245 250 255Leu Ala Trp Glu Gln Met Gly Arg Tyr Arg Cys Thr Val Glu Asn Pro260 265 270Val Thr Gln Leu Ile Met Tyr Met Asp Val Arg Ile Gln Ala Pro His275 280 285Glu Cys Ser Ser Ser Pro Pro Gly Ser Cys Phe Ala His Leu Pro Ala290 295 300Ser Met Pro Cys305<210> 25<211> 457<212> PRT<213> 人(Homo sapiens)<400> 25Met Asp Leu Ser Arg Pro Arg Trp Ser Leu Trp Arg Arg Val Phe Leu1 5 10 15Met Ala Ser Leu Leu Ala Cys Gly Ile Cys Gln Ala Ser Gly Gln Ile20 25 30Phe Ile Thr Gln Thr Leu Gly Ile Lys Gly Tyr Arg Thr Val Val Ala35 40 45Leu Asp Lys Val Pro Glu Asp Val Gln Glu Tyr Ser Trp Tyr Trp Gly50 55 60Ala Asn Asp Ser Ala Gly Asn Met Ile Ile Ser His Lys Pro Pro Ser65 70 75 80Ala Gln Gln Pro Gly Pro Met Tyr Thr Gly Arg Glu Arg Val Asn Arg85 90 95Glu Gly Ser Leu Leu Ile Arg Pro Thr Ala Leu Asn Asp Thr Gly Asn100 105 110Tyr Thr Val Arg Val Val Ala Gly Asn Glu Thr Gln Arg Ala Thr Gly115 120 125Trp Leu Glu Val Leu Glu Leu Gly Ser Asn Leu Gly Ile Ser Val Asn130 135 140Ala Ser Ser Leu Val Glu Asn Met Asp Ser Val Ala Ala Asp Cys Leu145 150 155 160Thr Asn Val Thr Asn Ile Thr Trp Tyr Val Asn Asp Val Pro Thr Ser165 170 175Ser Ser Asp Arg Met Thr Ile Ser Pro Asp Gly Lys Thr Leu Val Ile180 185 190Leu Arg Val Ser Arg Tyr Asp Arg Thr Ile Gln Cys Met Ile Glu Ser195 200 205Phe Pro Glu Ile Phe Gln Arg Ser Glu Arg Ile Ser Leu Thr Val Ala210 215 220Tyr Gly Pro Asp Tyr Val Leu Leu Arg Ser Asn Pro Asp Asp Phe Asn225 230 235 240Gly Ile Val Thr Ala Glu Ile Gly Ser Gln Val Glu Met Glu Cys Ile245 250 255Cys Tyr Ser Phe Leu Asp Leu Lys Tyr His Trp Ile His Asn Gly Ser260 265 270Leu Leu Asn Phe Ser Asp Ala Lys Met Asn Leu Ser Ser Leu Ala Trp275 280 285Glu Gln Met Gly Arg Tyr Arg Cys Thr Val Glu Asn Pro Val Thr Gln290 295 300Leu Ile Met Tyr Met Asp Val Arg Ile Gln Ala Pro His Glu Cys Pro305 310 315 320Leu Pro Ser Gly Ile Leu Pro Val Val His Arg Asp Phe Ser Ile Ser325 330 335Gly Ser Met Val Met Phe Leu Ile Met Leu Thr Val Leu Gly Gly Val340 345 350Tyr Ile Cys Gly Val Leu Ile His Ala Leu Ile Asn His Tyr Ser Ile355 360 365Arg Cys Pro His Cys Ser Gly Thr Arg Val Gly Cys Trp Leu Gly Ala370 375 380Gly Thr Gln Glu Pro Ala Leu Pro Pro Glu Gly Lys Gln Ser Gln Lys385 390 395 400Gly Arg Asp Lys Pro Gly Thr Arg Leu Ser Gly Ile Ile Trp Gly Arg405 410 415Gln Ile Ser Pro Gln Asp Leu Lys Leu Met Gly Ala Arg Glu Gly Leu420 425 430Glu Ser Ala Met Val Leu Asn Ser Cys Gly Val Ser Ser Ser Asn Phe435 440 445Pro Ser Leu Cys Val Tyr Lys Gly Tyr450 455<210> 26<211> 704<212> PRT<213> 人(Homo sapiens)<400> 26Met Leu His Asp Gly Leu Thr Ala Pro Asp Gly Cys Gly Ile Tyr Ser1 5 10 15Leu Thr Gly Arg Glu Val Leu Thr Pro Phe Pro Gly Leu Gly Thr Ala20 25 30Ala Ala Pro Ala Gln Gly Gly Ala His Leu Lys Gln Cys Asp Leu Leu35 40 45Lys Leu Ser Arg Arg Gln Lys Gln Leu Cys Arg Arg Glu Pro Gly Leu50 55 60Ala Glu Thr Leu Arg Asp Ala Ala His Leu Gly Leu Leu Glu Cys Gln65 70 75 80Phe Gln Phe Arg His Glu Arg Trp Asn Cys Ser Leu Glu Gly Arg Met85 90 95Gly Leu Leu Lys Arg Gly Phe Lys Glu Thr Ala Phe Leu Tyr Ala Val100 105 110Ser Ser Ala Ala Leu Thr His Thr Leu Ala Arg Ala Cys Ser Ala Gly115 120 125Arg Met Glu Arg Cys Thr Cys Asp Asp Ser Pro Gly Leu Glu Ser Arg130 135 140Gln Ala Trp Gln Trp Gly Val Cys Gly Asp Asn Leu Lys Tyr Ser Thr145 150 155 160Lys Phe Leu Ser Asn Phe Leu Gly Ser Lys Arg Gly Asn Lys Asp Leu165 170 175Arg Ala Arg Ala Asp Ala His Asn Thr His Val Gly Ile Lys Ala Val180 185 190Lys Ser Gly Leu Arg Thr Thr Cys Lys Cys His Gly Val Ser Gly Ser195 200 205Cys Ala Val Arg Thr Cys Trp Lys Gln Leu Ser Pro Phe Arg Glu Thr210 215 220Gly Gln Val Leu Lys Leu Arg Tyr Asp Ser Ala Val Lys Val Ser Ser225 230 235 240Ala Thr Asn Glu Ala Leu Gly Arg Leu Glu Leu Trp Ala Pro Ala Arg245 250 255Gln Gly Ser Leu Thr Lys Gly Leu Ala Pro Arg Ser Gly Asp Leu Val260 265 270Tyr Met Glu Asp Ser Pro Ser Phe Cys Arg Pro Ser Lys Tyr Ser Pro275 280 285Gly Thr Ala Gly Arg Val Cys Ser Arg Glu Ala Ser Cys Ser Ser Leu290 295 300Cys Cys Gly Arg Gly Tyr Asp Thr Gln Ser Arg Leu Val Ala Phe Ser305 310 315 320Cys His Cys Gln Val Gln Trp Cys Cys Tyr Val Glu Cys Gln Gln Cys325 330 335Val Gln Glu Glu Leu Val Tyr Thr Cys Lys His Ala Met Gly Pro Val340 345 350Gly Phe Pro Arg Gln Cys Gln Gly Ala Phe Phe Glu Ser Ser Pro Gly355 360 365Gln Thr Arg Ala Arg Leu Thr Gly Arg Glu Val Leu Thr Pro Phe Pro370 375 380Gly Leu Gly Thr Ala Ala Ala Pro Ala Gln Gly Gly Ala His Leu Lys385 390 395 400Gln Cys Asp Leu Leu Lys Leu Ser Arg Arg Gln Lys Gln Leu Cys Arg405 410 415Arg Glu Pro Gly Leu Ala Glu Thr Leu Arg Asp Ala Ala His Leu Gly420 425 430Leu Leu Glu Cys Gln Phe Gln Phe Arg His Glu Arg Trp Asn Cys Ser435 440 445Leu Glu Gly Arg Met Gly Leu Leu Lys Arg Gly Phe Lys Glu Thr Ala450 455 460Phe Leu Tyr Ala Val Ser Ser Ala Ala Leu Thr His Thr Leu Ala Arg465 470 475 480Ala Cys Ser Ala Gly Arg Met Glu Arg Cys Thr Cys Asp Asp Ser Pro485 490 495Gly Leu Glu Ser Arg Gln Ala Trp Gln Trp Gly Val Cys Gly Asp Asn500 505 510Leu Lys Tyr Ser Thr Lys Phe Leu Ser Asn Phe Leu Gly Ser Lys Arg515 520 525Gly Asn Lys Asp Leu Arg Ala Arg Ala Asp Ala His Asn Thr His Val530 535 540Gly Ile Lys Ala Val Lys Ser Gly Leu Arg Thr Thr Cys Lys Cys His545 550 555 560Gly Val Ser Gly Ser Cys Ala Val Arg Thr Cys Trp Lys Gln Leu Ser565 570 575Pro Phe Arg Glu Thr Gly Gln Val Leu Lys Leu Arg Tyr Asp Ser Ala580 585 590Val Lys Val Ser Ser Ala Thr Asn Glu Ala Leu Gly Arg Leu Glu Leu595 600 605Trp Ala Pro Ala Arg Gln Gly Ser Leu Thr Lys Gly Leu Ala Pro Arg610 615 620Ser Gly Asp Leu Val Tyr Met Glu Asp Ser Pro Ser Phe Cys Arg Pro625 630 635 640Ser Lys Tyr Ser Pro Gly Thr Ala Gly Arg Val Cys Ser Arg Glu Ala645 650 655Ser Cys Ser Ser Leu Cys Cys Gly Arg Gly Tyr Asp Thr Gln Ser Arg660 665 670Leu Val Ala Phe Ser Cys His Cys Gln Val Gln Trp Cys Cys Tyr Val675 680 685Glu Cys Gln Gln Cys Val Gln Glu Glu Leu Val Tyr Thr Cys Lys His690 695 700<210> 27<211> 361<212> PRT<213> 人(Homo sapiens)<400> 27Met Lys Pro Leu Arg Arg Pro Leu Pro Phe Ile Cys Pro Ser Pro Pro1 5 10 15Ser Pro Arg Leu Thr Cys Leu Pro Pro Leu Ala Leu Ser Ser Leu Thr20 25 30Gly Arg Glu Val Leu Thr Pro Phe Pro Gly Leu Gly Thr Ala Ala Ala35 40 45Pro Ala Gln Gly Gly Ala His Leu Lys Gln Cys Asp Leu Leu Lys Leu50 55 60Ser Arg Arg Gln Lys Gln Leu Cys Arg Arg Glu Pro Gly Leu Ala Glu65 70 75 80Thr Leu Arg Asp Ala Ala His Leu Gly Leu Leu Glu Cys Gln Phe Gln85 90 95Phe Arg His Glu Arg Trp Asn Cys Ser Leu Glu Gly Arg Met Gly Leu100 105 110Leu Lys Arg Gly Phe Lys Glu Thr Ala Phe Leu Tyr Ala Val Ser Ser115 120 125Ala Ala Leu Thr His Thr Leu Ala Arg Ala Cys Ser Ala Gly Arg Met130 135 140Glu Arg Cys Thr Cys Asp Asp Ser Pro Gly Leu Glu Ser Arg Gln Ala145 150 155 160Trp Gln Trp Gly Val Cys Gly Asp Asn Leu Lys Tyr Ser Thr Lys Phe165 170 175Leu Ser Asn Phe Leu Gly Ser Lys Arg Gly Asn Lys Asp Leu Arg Ala180 185 190Arg Ala Asp Ala His Asn Thr His Val Gly Ile Lys Ala Val Lys Ser195 200 205Gly Leu Arg Thr Thr Cys Lys Cys His Gly Val Ser Gly Ser Cys Ala210 215 220Val Arg Thr Cys Trp Lys Gln Leu Ser Pro Phe Arg Glu Thr Gly Gln225 230 235 240Val Leu Lys Leu Arg Tyr Asp Ser Ala Val Lys Val Ser Ser Ala Thr245 250 255Asn Glu Ala Leu Gly Arg Leu Glu Leu Trp Ala Pro Ala Arg Gln Gly260 265 270Ser Leu Thr Lys Gly Leu Ala Pro Arg Ser Gly Asp Leu Val Tyr Met275 280 285Glu Asp Ser Pro Ser Phe Cys Arg Pro Ser Lys Tyr Ser Pro Gly Thr290 295 300Ala Gly Arg Val Cys Ser Arg Glu Ala Ser Cys Ser Ser Leu Cys Cys305 310 315 320Gly Arg Gly Tyr Asp Thr Gln Ser Arg Leu Val Ala Phe Ser Cys His325 330 335Cys Gln Val Gln Trp Cys Cys Tyr Val Glu Cys Gln Gln Cys Val Gln340 345 350Glu Glu Leu Val Tyr Thr Cys Lys His355 360<210> 28<211> 365<212> PRT<213> 人(Homo sapiens)<400> 28Met Trp Leu Leu Leu Thr Thr Thr Cys Leu Ile Cys Gly Thr Leu Asn1 5 10 15Ala Gly Gly Phe Leu Asp Leu Glu Asn Glu Val Asn Pro Glu Val Trp20 25 30Met Asn Thr Ser Glu Ile Ile Ile Tyr Asn Gly Tyr Pro Ser Glu Glu35 40 45Tyr Glu Val Thr Thr Glu Asp Gly Tyr Ile Leu Leu Val Asn Arg Ile50 55 60Pro Tyr Gly Arg Thr His Ala Arg Ser Thr Ala Asp Ala Gly Tyr Asp65 70 75 80Val Trp Met Gly Asn Ser Arg Gly Asn Thr Trp Ser Arg Arg His Lys85 90 95Thr Leu Ser Glu Thr Asp Glu Lys Phe Trp Ala Phe Ser Phe Asp Glu100 105 110Met Ala Lys Tyr Asp Leu Pro Gly Val Ile Asp Phe Ile Val Asn Lys115 120 125Thr Gly Gln Glu Lys Leu Tyr Phe Ile Gly His Ser Leu Gly Thr Thr130 135 140Ile Gly Phe Val Ala Phe Ser Thr Met Pro Glu Leu Ala Gln Arg Ile145 150 155 160Lys Met Asn Phe Ala Leu Gly Pro Thr Ile Ser Phe Lys Tyr Pro Thr165 170 175Gly Ile Phe Thr Arg Phe Phe Leu Leu Pro Asn Ser Ile Ile Lys Ala180 185 190Val Phe Gly Thr Lys Gly Phe Phe Leu Glu Asp Lys Lys Thr Lys Ile195 200 205Ala Ser Thr Lys Ile Cys Asn Asn Lys Ile Leu Trp Leu Ile Cys Ser210 215 220Glu Phe Met Ser Leu Trp Ala Gly Ser Asn Lys Lys Asn Met Asn Gln225 230 235 240Ser Arg Met Asp Val Tyr Met Ser His Ala Pro Thr Gly Ser Ser Val245 250 255His Asn Ile Leu His Ile Lys Gln Leu Tyr His Ser Asp Glu Phe Arg260 265 270Ala Tyr Asp Trp Gly Asn Asp Ala Asp Asn Met Lys His Tyr Asn Gln275 280 285Ser His Pro Pro Ile Tyr Asp Leu Thr Ala Met Lys Val Pro Thr Ala290 295 300Ile Trp Ala Gly Gly His Asp Val Leu Val Thr Pro Gln Asp Val Ala305 310 315 320Arg Ile Leu Pro Gln Ile Lys Ser Leu His Tyr Phe Lys Leu Leu Pro325 330 335Asp Trp Asn His Phe Asp Phe Val Trp Gly Leu Asp Ala Pro Gln Arg340 345 350Met Tyr Ser Glu Ile Ile Ala Leu Met Lys Ala Tyr Ser355 360 365<210> 29<211> 397<212> PRT<213> 人(Homo sapiens)<400> 29Met Trp Gln Leu Leu Ala Ala Ala Cys Trp Met Leu Leu Leu Gly Ser1 5 10 15Met Tyr Gly Tyr Asp Lys Lys Gly Asn Asn Ala Asn Pro Glu Ala Asn20 25 30Met Asn Ile Ser Gln Ile Ile Ser Tyr Trp Gly Tyr Pro Tyr Glu Glu35 40 45Tyr Asp Val Thr Thr Lys Asp Gly Tyr Ile Leu Gly Ile Tyr Arg Ile50 55 60Pro His Gly Arg Gly Cys Pro Gly Arg Thr Ala Pro Lys Pro Ala Val65 70 75 80Tyr Leu Gln His Gly Leu Ile Ala Ser Ala Ser Asn Trp Ile Cys Asn85 90 95Leu Pro Asn Asn Ser Leu Ala Phe Leu Leu Ala Asp Ser Gly Tyr Asp100 105 110Val Trp Leu Gly Asn Ser Arg Gly Asn Thr Trp Ser Arg Lys His Leu115 120 125Lys Leu Ser Pro Lys Ser Pro Glu Tyr Trp Ala Phe Ser Leu Asp Glu
130 135 140Met Ala Lys Tyr Asp Leu Pro Ala Thr Ile Asn Phe Ile Ile Glu Lys145 150 155 160Thr Gly Gln Lys Arg Leu Tyr Tyr Val Gly His Ser Gln Gly Thr Thr165 170 175Ile Ala Phe Ile Ala Phe Ser Thr Asn Pro Glu Leu Ala Lys Lys Ile180 185 190Lys Ile Phe Phe Ala Leu Ala Pro Val Val Thr Val Lys Tyr Thr Gln195 200 205Ser Pro Met Lys Lys Leu Thr Thr Leu Ser Arg Arg Val Val Lys Val210 215 220Leu Phe Gly Asp Lys Met Phe His Pro His Thr Leu Phe Asp Gln Phe225 230 235 240Ile Ala Thr Lys Val Cys Asn Arg Lys Leu Phe Arg Arg Ile Cys Ser245 250 255Asn Phe Leu Phe Thr Leu Ser Gly Phe Asp Pro Gln Asn Leu Asn Met260 265 270Ser Arg Leu Asp Val Tyr Leu Ser His Asn Pro Ala Gly Thr Ser Val275 280 285Gln Asn Met Leu His Trp Ala Gln Leu Tyr His Ser Asp Glu Phe Arg290 295 300Ala Tyr Asp Trp Gly Asn Asp Ala Asp Asn Met Lys His Tyr Asn Gln305 310 315 320Ser His Pro Pro Ile Tyr Asp Leu Thr Ala Met Lys Val Pro Thr Ala325 330 335Ile Trp Ala Gly Gly His Asp Val Leu Val Thr Pro Gln Asp Val Ala340 345 350Arg Ile Leu Pro Gln Ile Lys Ser Leu His Tyr Phe Lys Leu Leu Pro355 360 365Asp Trp Asn His Phe Asp Phe Val Trp Gly Leu Asp Ala Pro Gln Arg370 375 380Met Tyr Ser Glu Ile Ile Ala Leu Met Lys Ala Tyr Ser385 390 395<210> 30<211> 3705<212> PRT<213> 人(Homo sapiens)<400> 30Met Ala Lys Arg Leu Cys Ala Gly Ser Ala Leu Cys Val Arg Gly Pro1 5 10 15Arg Gly Pro Ala Pro Leu Leu Leu Val Gly Leu Ala Leu Leu Gly Ala20 25 30Ala Arg Ala Arg Glu Glu Ala Gly Gly Gly Phe Ser Leu His Pro Pro35 40 45Tyr Phe Asn Leu Ala Glu Gly Ala Arg Ile Ala Ala Ser Ala Thr Cys50 55 60Gly Glu Glu Ala Pro Ala Arg Gly Ser Pro Arg Pro Thr Glu Asp Leu65 70 75 80Tyr Cys Lys Leu Val Gly Gly Pro Val Ala Gly Gly Asp Pro Asn Gln85 90 95Thr Ile Arg Gly Gln Tyr Cys Asp Ile Cys Thr Ala Ala Asn Ser Asn100 105 110Lys Ala His Pro Ala Ser Asn Ala Ile Asp Gly Thr Glu Arg Trp Trp115 120 125Gln Ser Pro Pro Leu Ser Arg Gly Leu Glu Tyr Asn Glu Val Asn Val130 135 140Thr Leu Asp Leu Gly Gln Val Phe His Val Ala Tyr Val Leu Ile Lys145 150 155 160Phe Ala Asn Ser Pro Arg Pro Asp Leu Trp Val Leu Glu Arg Ser Met165 170 175Asp Phe Gly Arg Thr Tyr Gln Pro Trp Gln Phe Phe Ala Ser Ser Lys180 185 190Arg Asp Cys Leu Glu Arg Phe Gly Pro Gln Thr Leu Glu Arg Ile Thr195 200 205Arg Asp Asp Ala Ala Ile Cys Thr Thr Glu Tyr Ser Arg Ile Val Pro210 215 220Leu Glu Asn Gly Glu Ile Val Val Ser Leu Val Asn Gly Arg Pro Gly225 230 235 240Ala Met Asn Phe Ser Tyr Ser Pro Leu Leu Arg Glu Phe Thr Lys Ala245 250 255Thr Asn Val Arg Leu Arg Phe Leu Arg Thr Asn Thr Leu Leu Gly His260 265 270Leu Met Gly Lys Ala Leu Arg Asp Pro Thr Val Thr Arg Arg Tyr Tyr275 280 285Tyr Ser Ile Lys Asp Ile Ser Ile Gly Gly Arg Cys Val Cys His Gly290 295 300His Ala Asp Ala Cys Asp Ala Lys Asp Pro Thr Asp Pro Phe Arg Leu305 310 315 320Gln Cys Thr Cys Gln His Asn Thr Cys Gly Gly Thr Cys Asp Arg Cys325 330 335Cys Pro Gly Phe Asn Gln Gln Pro Trp Lys Pro Ala Thr Ala Asn Ser340 345 350Ala Asn Glu Cys Gln Ser Cys Asn Cys Tyr Gly His Ala Thr Asp Cys355 360 365Tyr Tyr Asp Pro Glu Val Asp Arg Arg Arg Ala Ser Gln Ser Leu Asp370 375 380Gly Thr Tyr Gln Gly Gly Gly Val Cys Ile Asp Cys Gln His His Thr385 390 395 400Thr Gly Val Asn Cys Glu Arg Cys Leu Pro Gly Phe Tyr Arg Ser Pro405 410 415Asn His Pro Leu Asp Ser Pro His Val Cys Arg Arg Cys Asn Cys Glu420 425 430Ser Asp Phe Thr Asp Gly Thr Cys Glu Asp Leu Thr Gly Arg Cys Tyr435 440 445Cys Arg Pro Asn Phe Ser Gly Glu Arg Cys Asp Val Cys Ala Glu Gly450 455 460Phe Thr Gly Phe Pro Ser Cys Tyr Pro Thr Pro Ser Ser Ser Asn Asp465 470 475 480Thr Arg Glu Gln Val Leu Pro Ala Gly Gln Ile Val Asn Cys Asp Cys485 490 495Ser Ala Ala Gly Thr Gln Gly Asn Ala Cys Arg Lys Asp Pro Arg Val500 505 510Gly Arg Cys Leu Cys Lys Pro Asn Phe Gln Gly Thr His Cys Glu Leu515 520 525Cys Ala Pro Gly Phe Tyr Gly Pro Gly Cys Gln Pro Cys Gln Cys Ser530 535 540Ser Pro Gly Val Ala Asp Asp Arg Cys Asp Pro Asp Thr Gly Gln Cys545 550 555 560Arg Cys Arg Val Gly Phe Glu Gly Ala Thr Cys Asp Arg Cys Ala Pro565 570 575Gly Tyr Phe His Phe Pro Leu Cys Gln Leu Cys Gly Cys Ser Pro Ala580 585 590Gly Thr Leu Pro Glu Gly Cys Asp Glu Ala Gly Arg Cys Leu Cys Gln595 600 605Pro Glu Phe Ala Gly Pro His Cys Asp Arg Cys Arg Pro Gly Tyr His610 615 620Gly Phe Pro Asn Cys Gln Ala Cys Thr Cys Asp Pro Arg Gly Ala Leu625 630 635 640Asp Gln Leu Cys Gly Ala Gly Gly Leu Cys Arg Cys Arg Pro Gly Tyr645 650 655Thr Gly Thr Ala Cys Gln Glu Cys Ser Pro Gly Phe His Gly Phe Pro660 665 670Ser Cys Val Pro Cys His Cys Ser Ala Glu Gly Ser Leu His Ala Ala
675 680 685Cys Asp Pro Arg Ser Gly Gln Cys Ser Cys Arg Pro Arg Val Thr Gly690 695 700Leu Arg Cys Asp Thr Cys Val Pro Gly Ala Tyr Asn Phe Pro Tyr Cys705 710 715 720Glu Ala Gly Ser Cys His Pro Ala Gly Leu Ala Pro Val Asp Pro Ala725 730 735Leu Pro Glu Ala Gln Val Pro Cys Met Cys Arg Ala His Val Glu Gly740 745 750Pro Ser Cys Asp Arg Cys Lys Pro Gly Phe Trp Gly Leu Ser Pro Ser755 760 765Asn Pro Glu Gly Cys Thr Arg Cys Ser Cys Asp Leu Arg Gly Thr Leu770 775 780Gly Gly Val Ala Glu Cys Gln Pro Gly Thr Gly Gln Cys Phe Cys Lys785 790 795 800Pro His Val Cys Gly Gln Ala Cys Ala Ser Cys Lys Asp Gly Phe Phe805 810 815Gly Leu Asp Gln Ala Asp Tyr Phe Gly Cys Arg Ser Cys Arg Cys Asp820 825 830Ile Gly Gly Ala Leu Gly Gln Ser Cys Glu Pro Arg Thr Gly Val Cys835 840 845Arg Cys Arg Pro Asn Thr Gln Gly Pro Thr Cys Ser Glu Pro Ala Arg850 855 860Asp His Tyr Leu Pro Asp Leu His His Leu Arg Leu Glu Leu Glu Glu865 870 875 880Ala Ala Thr Pro Glu Gly His Ala Val Arg Phe Gly Phe Asn Pro Leu885 890 895Glu Phe Glu Asn Phe Ser Trp Arg Gly Tyr Ala Gln Met Ala Pro Val900 905 910Gln Pro Arg Ile Val Ala Arg Leu Asn Leu Thr Ser Pro Asp Leu Phe915 920 925Trp Leu Val Phe Arg Tyr Val Asn Arg Gly Ala Met Ser Val Ser Gly930 935 940Arg Val Ser Val Arg Glu Glu Gly Arg Ser Ala Thr Cys Ala Asn Cys945 950 955 960Thr Ala Gln Ser Gln Pro Val Ala Phe Pro Pro Ser Thr Glu Pro Ala965 970 975Phe Ile Thr Val Pro Gln Arg Gly Phe Gly Glu Pro Phe Val Leu Asn980 985 990Pro Gly Thr Trp Ala Leu Arg Val Glu Ala Glu Gly Val Leu Leu Asp995 10001005Tyr Val Val Leu Leu Pro Ser Ala Tyr Tyr Glu Ala Ala Leu Leu Gln101010151020Leu Arg Val Thr Glu Ala Cys Thr Tyr Arg Pro Ser Ala Gln Gln Ser1025103010351040Gly Asp Asn Cys Leu Leu Tyr Thr His Leu Pro Leu Asp Gly Phe Pro104510501055Ser Ala Ala Gly Leu Glu Ala Leu Cys Arg Gln Asp Asn Ser Leu Pro106010651070Arg Pro Cys Pro Thr Glu Gln Leu Ser Pro Ser His Pro Pro Leu Ile107510801085Thr Cys Thr Gly Ser Asp Val Asp Val Gln Leu Gln Val Ala Val Pro109010951100Gln Pro Gly Arg Tyr Ala Leu Val Val Glu Tyr Ala Asn Glu Asp Ala1105111011151120Arg Gln Glu Val Gly Val Ala Val His Thr Pro Gln Arg Ala Pro Gln112511301135Gln Gly Leu Leu Ser Leu His Pro Cys Leu Tyr Ser Thr Leu Cys Arg114011451150Gly Thr Ala Arg Asp Thr Gln Asp His Leu Ala Val Phe His Leu Asp115511601165Ser Glu Ala Ser Val Arg Leu Thr Ala Glu Gln Ala Arg Phe Phe Leu117011751180His Gly Val Thr Leu Val Pro Ile Glu Glu Phe Ser Pro Glu Phe Val1185119011951200Glu Pro Arg Val Ser Cys Ile Ser Ser His Gly Ala Phe Gly Pro Asn120512101215Ser Ala Ala Cys Leu Pro Ser Arg Phe Pro Lys Pro Pro Gln Pro Ile122012251230Ile Leu Arg Asp Cys Gln Val Ile Pro Leu Pro Pro Gly Leu Pro Leu123512401245Thr His Ala Gln Asp Leu Thr Pro Ala Met Ser Pro Ala Gly Pro Arg125012551260Pro Arg Pro Pro Thr Ala Val Asp Pro Asp Ala Glu Pro Thr Leu Leu1265127012751280Arg Glu Pro Gln Ala Thr Val Val Phe Thr Thr His Val Pro Thr Leu128512901295Gly Arg Tyr Ala Phe Leu Leu His Gly Tyr Gln Pro Ala His Pro Thr130013051310Phe Pro Val Glu Val Leu Ile Asn Ala Gly Arg Val Trp Gln Gly His131513201325Ala Asn Ala Ser Phe Cys Pro His Gly Tyr Gly Cys Arg Thr Leu Val133013351340Val Cys Glu Gly Gln Ala Leu Leu Asp Val Thr His Ser Glu Leu Thr1345135013551360Val Thr Val Arg Val Pro Lys Gly Arg Trp Leu Trp Leu Asp Tyr Val136513701375Leu Val Val Pro Glu Asn Val Tyr Ser Phe Gly Tyr Leu Arg Glu Glu138013851390Pro Leu Asp Lys Ser Tyr Asp Phe Ile Ser His Cys Ala Ala Gln Gly139514001405Tyr His Ile Ser Pro Ser Ser Ser Ser Leu Phe Cys Arg Asn Ala Ala141014151420Ala Ser Leu Ser Leu Phe Tyr Asn Asn Gly Ala Arg Pro Cys Gly Cys1425143014351440His Glu Val Gly Ala Thr Gly Pro Thr Cys Glu Pro Phe Gly Gly Gln144514501455Cys Pro Cys His Ala His Val Ile Gly Arg Asp Cys Ser Arg Cys Ala146014651470Thr Gly Tyr Trp Gly Phe Pro Asn Cys Arg Pro Cys Asp Cys Gly Ala147514801485Arg Leu Cys Asp Glu Leu Thr Gly Gln Cys Ile Cys Pro Pro Arg Thr149014951500Ile Pro Pro Asp Cys Leu Leu Cys Gln Pro Gln Thr Phe Gly Cys His1505151015151520Pro Leu Val Gly Cys Glu Glu Cys Asn Cys Ser Gly Pro Gly Ile Gln152515301535Glu Leu Thr Asp Pro Thr Cys Asp Thr Asp Ser Gly Gln Cys Lys Cys154015451550Arg Pro Asn Val Thr Gly Arg Arg Cys Asp Thr Cys Ser Pro Gly Phe155515601565His Gly Tyr Pro Arg Cys Arg Pro Cys Asp Cys His Glu Ala Gly Thr157015751580Ala Pro Gly Val Cys Asp Pro Leu Thr Gly Gln Cys Tyr Cys Lys Glu1585159015951600Asn Val Gln Gly Pro Lys Cys Asp Gln Cys Ser Leu Gly Thr Phe Ser160516101615Leu Asp Ala Ala Asn Pro Lys Gly Cys Thr Arg Cys Phe Cys Phe Gly162016251630Ala Thr Glu Arg Cys Arg Ser Ser Ser Tyr Thr Arg Gln Glu Phe Val163516401645Asp Met Glu Gly Trp Val Leu Leu Ser Thr Asp Arg Gln Val Val Pro165016551660His Glu Arg Gln Pro Gly Thr Glu Met Leu Arg Ala Asp Leu Arg His1665167016751680Val Pro Glu Ala Val Pro Glu Ala Phe Pro Glu Leu Tyr Trp Gln Ala
168516901695Pro Pro Ser Tyr Leu Gly Asp Arg Val Ser Ser Tyr Gly Gly Thr Leu170017051710Arg Tyr Glu Leu His Ser Glu Thr Gln Arg Gly Asp Val Phe Val Pro171517201725Met Glu Ser Arg Pro Asp Val Val Leu Gln Gly Asn Gln Met Ser Ile173017351740Thr Phe Leu Glu Pro Ala Tyr Pro Thr Pro Gly His Val His Arg Gly1745175017551760Gln Leu Gln Leu Val Glu Gly Asn Phe Arg His Thr Glu Thr Arg Asn176517701775Thr Val Ser Arg Glu Glu Leu Met Met Val Leu Ala Ser Leu Glu Gln178017851790Leu Gln Ile Arg Ala Leu Phe Ser Gln Ile Ser Ser Ala Val Phe Leu179518001805Arg Arg Val Ala Leu Glu Val Ala Ser Pro Ala Gly Gln Gly Ala Leu181018151820Ala Ser Asn Val Glu Leu Cys Leu Cys Pro Ala Ser Tyr Arg Gly Asp1825183018351840Ser Cys Gln Glu Cys Ala Pro Gly Phe Tyr Arg Asp Val Lys Gly Leu184518501855Phe Leu Gly Arg Cys Val Pro Cys Gln Cys His Gly His Ser Asp Arg186018651870Cys Leu Pro Gly Ser Gly Val Cys Val Asp Cys Gln His Asn Thr Glu187518801885Gly Ala His Cys Glu Arg Cys Gln Ala Gly Phe Val Ser Ser Arg Asp189018951900Asp Pro Ser Ala Pro Cys Val Ser Cys Pro Cys Pro Leu Ser Val Pro1905191019151920Ser Asn Asn Phe Ala Glu Gly Cys Val Leu Arg Gly Gly Arg Thr Gln192519301935Cys Leu Cys Lys Pro Gly Tyr Ala Gly Ala Ser Cys Glu Arg Cys Ala194019451950Pro Gly Phe Phe Gly Asn Pro Leu Val Leu Gly Ser Ser Cys Gln Pro195519601965Cys Asp Cys Ser Gly Asn Gly Asp Pro Asn Leu Leu Phe Ser Asp Cys197019751980Asp Pro Leu Thr Gly Ala Cys Arg Gly Cys Leu Arg His Thr Thr Gly1985199019952000Pro Arg Cys Glu Ile Cys Ala Pro Gly Phe Tyr Gly Asn Ala Leu Leu200520102015Pro Gly Asn Cys Thr Arg Cys Asp Cys Thr Pro Cys Gly Thr Glu Ala202020252030Cys Asp Pro His Ser Gly His Cys Leu Cys Lys Ala Gly Val Thr Gly203520402045Arg Arg Cys Asp Arg Cys Gln Glu Gly His Phe Gly Phe Asp Gly Cys205020552060Gly Gly Cys Arg Pro Cys Ala Cys Gly Pro Ala Ala Glu Gly Ser Glu2065207020752080Cys His Pro Gln Ser Gly Gln Cys His Cys Arg Pro Gly Thr Met Gly208520902095Pro Gln Cys Arg Glu Cys Ala Pro Gly Tyr Trp Gly Leu Pro Glu Gln210021052110Gly Cys Arg Arg Cys Gln Cys Pro Gly Gly Arg Cys Asp Pro His Thr211521202125Gly Arg Cys Asn Cys Pro Pro Gly Leu Ser Gly Glu Arg Cys Asp Thr213021352140Cys Ser Gln Gln His Gln Val Pro Val Pro Gly Gly Pro Val Gly His2145215021552160Ser Ile His Cys Glu Val Cys Asp His Cys Val Val Leu Leu Leu Asp216521702175Asp Leu Glu Arg Ala Gly Ala Leu Leu Pro Ala Ile His Glu Gln Leu
218021852190Arg Gly Ile Asn Ala Ser Ser Met Ala Trp Ala Arg Leu His Arg Leu219522002205Asn Ala Ser Ile Ala Asp Leu Gln Ser Gln Leu Arg Ser Pro Leu Gly221022152220Pro Arg His Glu Thr Ala Gln Gln Leu Glu Val Leu Glu Gln Gln Ser2225223022352240Thr Ser Leu Gly Gln Asp Ala Arg Arg Leu Gly Gly Gln Ala Gly Ala224522502255Pro Arg Pro Pro Arg Ala Pro Gly Gly Phe His Leu Tyr Gln Ala Ser226022652270Gln Leu Leu Ala Gly Thr Glu Ala Thr Leu Gly His Ala Lys Thr Leu227522802285Leu Ala Ala Ile Arg Ala Val Asp Arg Thr Leu Ser Glu Leu Met Ser229022952300Gln Thr Gly His Leu Gly Leu Ala Asn Ala Ser Ala Pro Ser Gly Glu2305231023152320Gln Leu Leu Arg Thr Leu Ala Glu Val Glu Arg Leu Leu Trp Glu Met232523302335Arg Ala Arg Asp Leu Gly Ala Pro Gln Ala Ala Ala Glu Ala Glu Leu234023452350Ala Ala Ala Gln Arg Leu Leu Ala Arg Val Gln Glu Gln Leu Ser Ser235523602365Leu Trp Glu Glu Asn Gln Ala Leu Ala Thr Gln Thr Arg Asp Arg Leu237023752380Ala Gln His Glu Ala Gly Leu Met Asp Leu Arg Glu Ala Leu Asn Arg2385239023952400Ala Val Asp Ala Thr Arg Glu Ala Gln Glu Leu Asn Ser Arg Asn Gln240524102415Glu Arg Leu Glu Glu Ala Leu Gln Arg Lys Gln Glu Leu Ser Arg Asp242024252430Asn Ala Thr Leu Gln Ala Thr Leu His Ala Ala Arg Asp Thr Leu Ala243524402445Ser Val Phe Arg Leu Leu His Ser Leu Asp Gln Ala Lys Glu Glu Leu245024552460Glu Arg Leu Ala Ala Ser Leu Asp Gly Ala Arg Thr Pro Leu Leu Gln2465247024752480Arg Met Gln Thr Phe Ser Pro Ala Gly Ser Lys Leu Arg Leu Val Glu24852490 2495Ala Ala Glu Ala His Ala Gln Gln Leu Gly Gln Leu Ala Leu Asn Leu250025052510Ser Ser Ile Ile Leu Asp Val Asn Gln Asp Arg Leu Thr Gln Arg Ala251525202525Ile Glu Ala Ser Asn Ala Tyr Ser Arg Ile Leu Gln Ala Val Gln Ala253025352540Ala Glu Asp Ala Ala Gly Gln Ala Leu Gln Gln Ala Asp His Thr Trp2545255025552560Ala Thr Val Val Arg Gln Gly Leu Val Asp Arg Ala Gln Gln Leu Leu256525702575Ala Asn Ser Thr Ala Leu Glu Glu Ala Met Leu Gln Glu Gln Gln Arg258025852590Leu Gly Leu Val Trp Ala Ala Leu Gln Gly Ala Arg Thr Gln Leu Arg259526002605Asp Val Arg Ala Lys Lys Asp Gln Leu Glu Ala His Ile Gln Ala Ala261026152620Gln Ala Met Leu Ala Met Asp Thr Asp Glu Thr Ser Lys Lys Ile Ala2625263026352640His Ala Lys Ala Val Ala Ala Glu Ala Gln Asp Thr Ala Thr Arg Val264526502655Gln Ser Gln Leu Gln Ala Met Gln Glu Asn Val Glu Arg Trp Gln Gly266026652670Gln Tyr Glu Gly Leu Arg Gly Gln Asp Leu Gly Gln Ala Val Leu Asp
267526802685Ala Gly His Ser Val Ser Thr Leu Glu Lys Thr Leu Pro Gln Leu Leu269026952700Ala Lys Leu Ser Ile Leu Glu Asn Arg Gly Val His Asn Ala Ser Leu2705271027152720Ala Leu Ser Ala Ser Ile Gly Arg Val Arg Glu Leu Ile Ala Gln Ala272527302735Arg Gly Ala Ala Ser Lys Val Lys Val Pro Met Lys Phe Asn Gly Arg274027452750Ser Gly Val Gln Leu Arg Thr Pro Arg Asp Leu Ala Asp Leu Ala Ala275527602765Tyr Thr Ala Leu Lys Phe Tyr Leu Gln Gly Pro Glu Pro Glu Pro Gly277027752780Gln Gly Thr Glu Asp Arg Phe Val Met Tyr Met Gly Ser Arg Gln Ala2785279027952800Thr Gly Asp Tyr Met Gly Val Ser Leu Arg Asp Lys Lys Val His Trp280528102815Val Tyr Gln Leu Gly Glu Ala Gly Pro Ala Val Leu Ser Ile Asp Glu282028252830Asp Ile Gly Glu Gln Phe Ala Ala Val Ser Leu Asp Arg Thr Leu Gln283528402845Phe Gly His Met Ser Val Thr Val Glu Arg Gln Met Ile Gln Glu Thr285028552860Lys Gly Asp Thr Val Ala Pro Gly Ala Glu Gly Leu Leu Asn Leu Arg2865287028752880Pro Asp Asp Phe Val Phe Tyr Val Gly Gly Tyr Pro Ser Thr Phe Thr2885 2890 2895Pro Pro Pro Leu Leu Arg Phe Pro Gly Tyr Arg Gly Cys Ile Glu Met290029052910Asp Thr Leu Asn Glu Glu Val Val Ser Leu Tyr Asn Phe Glu Arg Thr2915 2920 2925Phe Gln Leu Asp Thr Ala Val Asp Arg Pro Cys Ala Arg Ser Lys Ser293029352940Thr Gly Asp Pro Trp Leu Thr Asp Gly Ser Tyr Leu Asp Gly Thr Gly2945295029552960Phe Ala Arg Ile Ser Phe Asp Ser Gln Ile Ser Thr Thr Lys Arg Phe296529702975Glu Gln Glu Leu Arg Leu Val Ser Tyr Ser Gly Val Leu Phe Phe Leu298029852990Lys Gln Gln Ser Gln Phe Leu Cys Leu Ala Val Gln Glu Gly Ser Leu299530003005Val Leu Leu Tyr Asp Phe Gly Ala Gly Leu Lys Lys Ala Val Pro Leu301030153020Gln Pro Pro Pro Pro Leu Thr Ser Ala Ser Lys Ala Ile Gln Val Phe3025303030353040Leu Leu Gly Gly Ser Arg Lys Arg Val Leu Val Arg Val Glu Arg Ala304530503055Thr Val Tyr Ser Val Glu Gln Asp Asn Asp Leu Glu Leu Ala Asp Ala306030653070Tyr Tyr Leu Gly Gly Val Pro Pro Asp Gln Leu Pro Pro Ser Leu Arg307530803085Arg Leu Phe Pro Thr Gly Gly Ser Val Arg Gly Cys Val Lys Gly Ile309030953100Lys Ala Leu Gly Lys Tyr Val Asp Leu Lys Arg Leu Asn Thr Thr Gly3105311031153120Val Ser Ala Gly Cys Thr Ala Asp Leu Leu Val Gly Arg Ala Met Thr312531303135Phe His Gly His Gly Phe Leu Arg Leu Ala Leu Ser Asn Val Ala Pro314031453150Leu Thr Gly Asn Val Tyr Ser Gly Phe Gly Phe His Ser Ala Gln Asp315531603165Ser Ala Leu Leu Tyr Tyr Arg Ala Ser Pro Asp Gly Leu Cys Gln Val317031753180Ser Leu Gln Gln Gly Arg Val Ser Leu Gln Leu Leu Arg Thr Glu Val3185319031953200Lys Thr Gln Ala Gly Phe Ala Asp Gly Ala Pro His Tyr Val Ala Phe320532103215Tyr Ser Asn Ala Thr Gly Val Trp Leu Tyr Val Asp Asp Gln Leu Gln322032253230Gln Met Lys Pro His Arg Gly Pro Pro Pro Glu Leu Gln Pro Gln Pro323532403245Glu Gly Pro Pro Arg Leu Leu Leu Gly Gly Leu Pro Glu Ser Gly Thr325032553260Ile Tyr Asn Phe Ser Gly Cys Ile Ser Asn Val Phe Val Gln Arg Leu3265327032753280Leu Gly Pro Gln Arg Val Phe Asp Leu Gln Gln Asn Leu Gly Ser Val328532903295Asn Val Ser Thr Gly Cys Ala Pro Ala Leu Gln Ala Gln Thr Pro Gly330033053310Leu Gly Pro Arg Gly Leu Gln Ala Thr Ala Arg Lys Ala Ser Arg Arg331533203325Ser Arg Gln Pro Ala Arg His Pro Ala Cys Met Leu Pro Pro His Leu333033353340Arg Thr Thr Arg Asp Ser Tyr Gln Phe Gly Gly Ser Leu Ser Ser His3345335033553360Leu Glu Phe Val Gly Ile Leu Ala Arg His Arg Asn Trp Pro Ser Leu336533703375Ser Met His Val Leu Pro Arg Ser Ser Arg Gly Leu Leu Leu Phe Thr338033853390Ala Arg Leu Arg Pro Gly Ser Pro Ser Leu Ala Leu Phe Leu Ser Asn339534003405Gly His Phe Val Ala Gln Met Glu Gly Leu Gly Thr Arg Leu Arg Ala341034153420Gln Ser Arg Gln Arg Ser Arg Pro Gly Arg Trp His Lys Val Ser Val3425343034353440Arg Trp Glu Lys Asn Arg Ile Leu Leu Val Thr Asp Gly Ala Arg Ala344534503455Trp Ser Gln Glu Gly Pro His Arg Gln His Gln Gly Ala Glu His Pro346034653470Gln Pro His Thr Leu Phe Val Gly Gly Leu Pro Ala Ser Ser His Ser347534803485Ser Lys Leu Pro Val Thr Val Gly Phe Ser Gly Cys Val Lys Arg Leu349034953500Arg Leu His Gly Arg Pro Leu Gly Ala Pro Thr Arg Met Ala Gly Val3505351035153520Thr Pro Cys Ile Leu Gly Pro Leu Glu Ala Gly Leu Phe Phe Pro Gly352535303535Ser Gly Gly Val Ile Thr Leu Asp Leu Pro Gly Ala Thr Leu Pro Asp354035453550Val Gly Leu Glu Leu Glu Val Arg Pro Leu Ala Val Thr Gly Leu Ile355535603565Phe His Leu Gly Gln Ala Arg Thr Pro Pro Tyr Leu Gln Leu Gln Val357035753580Thr Glu Lys Gln Val Leu Leu Arg Ala Asp Asp Gly Ala Gly Glu Phe3585359035953600Ser Thr Ser Val Thr Arg Pro Ser Val Leu Cys Asp Gly Gln Trp His360536103615Arg Leu Ala Val Met Lys Ser Gly Asn Val Leu Arg Leu Glu Val Asp362036253630Ala Gln Ser Asn His Thr Val Gly Pro Leu Leu Ala Ala Ala Ala Gly363536403645Ala Pro Ala Pro Leu Tyr Leu Gly Gly Leu Pro Glu Pro Met Ala Val365036553660Gln Pro Trp Pro Pro Ala Tyr Cys Gly Cys Met Arg Arg Leu Ala Val3665 3670 36753680Asn Arg Ser Pro Val Ala Met Thr Arg Ser Val Glu Val His Gly Ala
36853690 3695Val Gly Ala Ser Gly Cys Pro Ala Ala37003705<210> 31<211> 3696<212> PRT<213> 人(Homo sapiens)<400> 31Met Ala Lys Arg Leu Cys Ala Gly Ser Ala Leu Cys Val Arg Gly Pro1 5 10 15Arg Gly Pro Ala Pro Leu Leu Leu Val Gly Leu Ala Leu Leu Gly Ala20 25 30Ala Arg Ala Arg Glu Glu Ala Gly Gly Gly Phe Ser Leu His Pro Pro35 40 45Tyr Phe Asn Leu Ala Glu Gly Ala Arg Ile Ala Ala Ser Ala Thr Cys50 55 60Gly Glu Glu Ala Pro Ala Arg Gly Ser Pro Arg Pro Thr Glu Asp Leu65 70 75 80Tyr Cys Lys Leu Val Gly Gly Pro Val Ala Gly Gly Asp Pro Asn Gln85 90 95Thr Ile Arg Gly Gln Tyr Cys Asp Ile Cys Thr Ala Ala Asn Ser Asn100 105 110Lys Ala His Pro Ala Ser Asn Ala Ile Asp Gly Thr Glu Arg Trp Trp115 120 125Gln Ser Pro Pro Leu Ser Arg Gly Leu Glu Tyr Asn Glu Val Asn Val130 135 140Thr Leu Asp Leu Gly Gln Val Phe His Val Ala Tyr Val Leu Ile Lys145 150 155 160Phe Ala Asn Ser Pro Arg Pro Asp Leu Trp Val Leu Glu Arg Ser Met165 170 175Asp Phe Gly Arg Thr Tyr Gln Pro Trp Gln Phe Phe Ala Ser Ser Lys180 185 190Arg Asp Cys Leu Glu Arg Phe Gly Pro Gln Thr Leu Glu Arg Ile Thr195 200 205Arg Asp Asp Ala Ala Ile Cys Thr Thr Glu Tyr Ser Arg Ile Val Pro210 215 220Leu Glu Asn Gly Glu Ile Val Val Ser Leu Val Asn Gly Arg Pro Gly225 230 235 240Ala Met Asn Phe Ser Tyr Ser Pro Leu Leu Arg Glu Phe Thr Lys Ala245 250 255Thr Asn Val Arg Leu Arg Phe Leu Arg Thr Asn Thr Leu Leu Gly His260 265 270Leu Met Gly Lys Ala Leu Arg Asp Pro Thr Val Thr Arg Arg Tyr Tyr275 280 285Tyr Ser Ile Lys Asp Ile Ser Ile Gly Gly Arg Cys Val Cys His Gly290 295 300His Ala Asp Ala Cys Asp Ala Lys Asp Pro Thr Asp Pro Phe Arg Leu305 310 315 320Gln Cys Thr Cys Gln His Asn Thr Cys Gly Gly Thr Cys Asp Arg Cys325 330 335Cys Pro Gly Phe Asn Gln Gln Pro Trp Lys Pro Ala Thr Ala Asn Ser340 345 350Ala Asn Glu Cys Gln Ser Cys Asn Cys Tyr Gly His Ala Thr Asp Cys355 360 365Tyr Tyr Asp Pro Glu Val Asp Arg Arg Arg Ala Ser Gln Ser Leu Asp370 375 380Gly Thr Tyr Gln Gly Gly Gly Val Cys Ile Asp Cys Gln His His Thr385 390 395 400Thr Gly Val Asn Cys Glu Arg Cys Leu Pro Gly Phe Tyr Arg Ser Pro405 410 415Asn His Pro Leu Asp Ser Pro His Val Cys Arg Arg Cys Asn Cys Glu420 425 430Ser Asp Phe Thr Asp Gly Thr Cys Glu Asp Leu Thr Gly Arg Cys Tyr435 440 445Cys Arg Pro Asn Phe Ser Gly Glu Arg Cys Asp Val Cys Ala Glu Gly450 455 460Phe Thr Gly Phe Pro Ser Cys Tyr Pro Thr Pro Ser Ser Ser Asn Asp465 470 475 480Thr Arg Glu Gln Val Leu Pro Ala Gly Gln Ile Val Asn Cys Asp Cys485 490 495Ser Ala Ala Gly Thr Gln Gly Asn Ala Cys Arg Lys Asp Pro Arg Val500 505 510Gly Arg Cys Leu Cys Lys Pro Asn Phe Gln Gly Thr His Cys Glu Leu515 520 525Cys Ala Pro Gly Phe Tyr Gly Pro Gly Cys Gln Pro Cys Gln Cys Ser530 535 540Ser Pro Gly Val Ala Asp Asp Arg Cys Asp Pro Asp Thr Gly Gln Cys545 550 555 560Arg Cys Arg Val Gly Phe Glu Gly Ala Thr Cys Asp Arg Cys Ala Pro565 570 575Gly Tyr Phe His Phe Pro Leu Cys Gln Leu Cys Gly Cys Ser Pro Ala580 585 590Gly Thr Leu Pro Glu Gly Cys Asp Glu Ala Gly Arg Cys Leu Cys Gln595 600 605Pro Glu Phe Ala Gly Pro His Cys Asp Arg Cys Arg Pro Gly Tyr His610 615 620Gly Phe Pro Asn Cys Gln Ala Cys Thr Cys Asp Pro Arg Gly Ala Leu625 630 635 640Asp Gln Leu Cys Gly Ala Gly Gly Leu Cys Arg Cys Arg Pro Gly Tyr645 650 655Thr Gly Thr Ala Cys Gln Glu Cys Ser Pro Gly Phe His Gly Phe Pro660 665 670Ser Cys Val Pro Cys His Cys Ser Ala Glu Gly Ser Leu His Ala Ala675 680 685Cys Asp Pro Arg Ser Gly Gln Cys Ser Cys Arg Pro Arg Val Thr Gly690 695 700Leu Arg Cys Asp Thr Cys Val Pro Gly Ala Tyr Asn Phe Pro Tyr Cys705 710 715 720Glu Ala Gly Ser Cys His Pro Ala Gly Leu Ala Pro Val Asp Pro Ala725 730 735Leu Pro Glu Ala Gln Val Pro Cys Met Cys Arg Ala His Val Glu Gly740 745 750Pro Ser Cys Asp Arg Cys Lys Pro Gly Phe Trp Gly Leu Ser Pro Ser755 760 765Asn Pro Glu Gly Cys Thr Arg Cys Ser Cys Asp Leu Arg Gly Thr Leu770 775 780Gly Gly Val Ala Glu Cys Gln Pro Gly Thr Gly Gln Cys Phe Cys Lys785 790 795 800Pro His Val Cys Gly Gln Ala Cys Ala Ser Cys Lys Asp Gly Phe Phe805 810 815Gly Leu Asp Gln Ala Asp Tyr Phe Gly Cys Arg Ser Cys Arg Cys Asp820 825 830Ile Gly Gly Ala Leu Gly Gln Ser Cys Glu Pro Arg Thr Gly Val Cys835 840 845Arg Cys Arg Pro Asn Thr Gln Gly Pro Thr Cys Ser Glu Pro Ala Arg850 855 860Asp His Tyr Leu Pro Asp Leu His His Leu Arg Leu Glu Leu Glu Glu865 870 875 880Ala Ala Thr Pro Glu Gly His Ala Val Arg Phe Gly Phe Asn Pro Leu885 890 895Glu Phe Glu Asn Phe Ser Trp Arg Gly Tyr Ala Gln Met Ala Pro Val900 905 910Gln Pro Arg Ile Val Ala Arg Leu Asn Leu Thr Ser Pro Asp Leu Phe
915 920 925Trp Leu Val Phe Arg Tyr Val Asn Arg Gly Ala Met Ser Val Ser Gly930 935 940Arg Val Ser Val Arg Glu Glu Gly Arg Ser Ala Thr Cys Ala Asn Cys945 950 955 960Thr Ala Gln Ser Gln Pro Val Ala Phe Pro Pro Ser Thr Glu Pro Ala965 970 975Phe Ile Thr Val Pro Gln Arg Gly Phe Gly Glu Pro Phe Val Leu Asn980 985 990Pro Gly Thr Trp Ala Leu Arg Val Glu Ala Glu Gly Val Leu Leu Asp995 10001005Tyr Val Val Leu Leu Pro Ser Ala Tyr Tyr Glu Ala Ala Leu Leu Gln101010151020Leu Arg Val Thr Glu Ala Cys Thr Tyr Arg Pro Ser Ala Gln Gln Ser1025103010351040Gly Asp Asn Cys Leu Leu Tyr Thr His Leu Pro Leu Asp Gly Phe Pro104510501055Ser Ala Ala Gly Leu Glu Ala Leu Cys Arg Gln Asp Asn Ser Leu Pro106010651070Arg Pro Cys Pro Thr Glu Gln Leu Ser Pro Ser His Pro Pro Leu Ile107510801085Thr Cys Thr Gly Ser Asp Val Asp Val Gln Leu Gln Val Ala Val Pro109010951100Gln Pro Gly Arg Tyr Ala Leu Val Val Glu Tyr Ala Asn Glu Asp Ala1105111011151120Arg Gln Glu Val Gly Val Ala Val His Thr Pro Gln Arg Ala Pro Gln112511301135Gln Gly Leu Leu Ser Leu His Pro Cys Leu Tyr Ser Thr Leu Cys Arg114011451150Gly Thr Ala Arg Asp Thr Gln Asp His Leu Ala Val Phe His Leu Asp115511601165Ser Glu Ala Ser Val Arg Leu Thr Ala Glu Gln Ala Arg Phe Phe Leu117011751180His Gly Val Thr Leu Val Pro Ile Glu Glu Phe Ser Pro Glu Phe Val1185119011951200Glu Pro Arg Val Ser Cys Ile Ser Ser His Gly Ala Phe Gly Pro Asn120512101215Ser Ala Ala Cys Leu Pro Ser Arg Phe Pro Lys Pro Pro Gln Pro Ile122012251230Ile Leu Arg Asp Cys Gln Val Ile Pro Leu Pro Pro Gly Leu Pro Leu123512401245Thr His Ala Gln Asp Leu Thr Pro Ala Met Ser Pro Ala Gly Pro Arg125012551260Pro Arg Pro Pro Thr Ala Val Asp Pro Asp Ala Glu Pro Thr Leu Leu1265127012751280Arg Glu Pro Gln Ala Thr Val Val Phe Thr Thr His Val Pro Thr Leu128512901295Gly Arg Tyr Ala Phe Leu Leu His Gly Tyr Gln Pro Ala His Pro Thr130013051310Phe Pro Val Glu Val Leu Ile Asn Ala Gly Arg Val Trp Gln Gly His131513201325Ala Asn Ala Ser Phe Cys Pro His Gly Tyr Gly Cys Arg Thr Leu Val133013351340Val Cys Glu Gly Gln Ala Leu Leu Asp Val Thr His Ser Glu Leu Thr1345135013551360Val Thr Val Arg Val Pro Lys Gly Arg Trp Leu Trp Leu Asp Tyr Val136513701375Leu Val Val Pro Glu Asn Val Tyr Ser Phe Gly Tyr Leu Arg Glu Glu138013851390Pro Leu Asp Lys Ser Tyr Asp Phe Ile Ser His Cys Ala Ala Gln Gly139514001405Tyr His Ile Ser Pro Ser Ser Ser Ser Leu Phe Cys Arg Asn Ala Ala141014151420Ala Ser Leu Ser Leu Phe Tyr Asn Asn Gly Ala Arg Pro Cys Gly Cys1425143014351440His Glu Val Gly Ala Thr Gly Pro Thr Cys Glu Pro Phe Gly Gly Gln144514501455Cys Pro Cys His Ala His Val Ile Gly Arg Asp Cys Ser Arg Cys Ala146014651470Thr Gly Tyr Trp Gly Phe Pro Asn Cys Arg Pro Cys Asp Cys Gly Ala147514801485Arg Leu Cys Asp Glu Leu Thr Gly Gln Cys Ile Cys Pro Pro Arg Thr149014951500Ile Pro Pro Asp Cys Leu Leu Cys Gln Pro Gln Thr Phe Gly Cys His1505151015151520Pro Leu Val Gly Cys Glu Glu Cys Asn Cys Ser Gly Pro Gly Ile Gln152515301535Glu Leu Thr Asp Pro Thr Cys Asp Thr Asp Ser Gly Gln Cys Lys Cys154015451550Arg Pro Asn Val Thr Gly Arg Arg Cys Asp Thr Cys Ser Pro Gly Phe155515601565His Gly Tyr Pro Arg Cys Arg Pro Cys Asp Cys His Glu Ala Gly Thr157015751580Ala Pro Gly Val Cys Asp Pro Leu Thr Gly Gln Cys Tyr Cys Lys Glu1585159015951600Asn Val Gln Gly Pro Lys Cys Asp Gln Cys Ser Leu Gly Thr Phe Ser160516101615Leu Asp Ala Ala Asn Pro Lys Gly Cys Thr Arg Cys Phe Cys Phe Gly162016251630Ala Thr Glu Arg Cys Arg Ser Ser Ser Tyr Thr Arg Gln Glu Phe Val163516401645Asp Met Glu Gly Trp Val Leu Leu Ser Thr Asp Arg Gln Val Val Pro165016551660His Glu Arg Gln Pro Gly Thr Glu Met Leu Arg Ala Asp Leu Arg His1665167016751680Val Pro Glu Ala Val Pro Glu Ala Phe Pro Glu Leu Tyr Trp Gln Ala168516901695Pro Pro Ser Tyr Leu Gly Asp Arg Val Ser Ser Tyr Gly Gly Thr Leu170017051710Arg Tyr Glu Leu His Ser Glu Thr Gln Arg Gly Asp Val Phe Val Pro171517201725Met Glu Ser Arg Pro Asp Val Val Leu Gln Gly Asn Gln Met Ser Ile173017351740Thr Phe Leu Glu Pro Ala Tyr Pro Thr Pro Gly His Val His Arg Gly1745175017551760Gln Leu Gln Leu Val Glu Gly Asn Phe Arg His Thr Glu Thr Arg Asn176517701775Thr Val Ser Arg Glu Glu Leu Met Met Val Leu Ala Ser Leu Glu Gln178017851790Leu Gln Ile Arg Ala Leu Phe Ser Gln Ile Ser Ser Ala Val Phe Leu179518001805Arg Arg Val Ala Leu Glu Val Ala Ser Pro Ala Gly Gln Gly Ala Leu181018151820Ala Ser Asn Val Glu Leu Cys Leu Cys Pro Ala Ser Tyr Arg Gly Asp1825183018351840Ser Cys Gln Glu Cys Ala Pro Gly Phe Tyr Arg Asp Val Lys Gly Leu184518501855Phe Leu Gly Arg Cys Val Pro Cys Gln Cys His Gly His Ser Asp Arg186018651870Cys Leu Pro Gly Ser Gly Val Cys Val Asp Cys Gln His Asn Thr Glu187518801885Gly Ala His Cys Glu Arg Cys Gln Ala Gly Phe Val Ser Ser Arg Asp189018951900Asp Pro Ser Ala Pro Cys Val Ser Cys Pro Cys Pro Leu Ser Val Pro1905191019151920Ser Asn Asn Phe Ala Glu Gly Cys Val Leu Arg Gly Gly Arg Thr Gln192519301935Cys Leu Cys Lys Pro Gly Tyr Ala Gly Ala Ser Cys Glu Arg Cys Ala194019451950Pro Gly Phe Phe Gly Asn Pro Leu Val Leu Gly Ser Ser Cys Gln Pro19551960 1965Cys Asp Cys Ser Gly Asn Gly Asp Pro Asn Leu Leu Phe Ser Asp Cys197019751980Asp Pro Leu Thr Gly Ala Cys Arg Gly Cys Leu Arg His Thr Thr Gly1985199019952000Pro Arg Cys Glu Ile Cys Ala Pro Gly Phe Tyr Gly Asn Ala Leu Leu200520102015Pro Gly Asn Cys Thr Arg Cys Asp Cys Thr Pro Cys Gly Thr Glu Ala202020252030Cys Asp Pro His Ser Gly His Cys Leu Cys Lys Ala Gly Val Thr Gly203520402045Arg Arg Cys Asp Arg Cys Gln Glu Gly His Phe Gly Phe Asp Gly Cys205020552060Gly Gly Cys Arg Pro Cys Ala Cys Gly Pro Ala Ala Glu Gly Ser Glu2065207020752080Cys His Pro Gln Ser Gly Gln Cys His Cys Arg Pro Gly Thr Met Gly208520902095Pro Gln Cys Arg Glu Cys Ala Pro Gly Tyr Trp Gly Leu Pro Glu Gln210021052110Gly Cys Arg Arg Cys Gln Cys Pro Gly Gly Arg Cys Asp Pro His Thr211521202125Gly Arg Cys Asn Cys Pro Pro Gly Leu Ser Gly Glu Arg Cys Asp Thr213021352140Cys Ser Gln Gln His Gln Val Pro Val Pro Gly Gly Pro Val Gly His2145215021552160Ser Ile His Cys Glu Val Cys Asp His Cys Val Val Leu Leu Leu Asp216521702175Asp Leu Glu Arg Ala Gly Ala Leu Leu Pro Ala Ile His Glu Gln Leu218021852190Arg Gly Ile Asn Ala Ser Ser Met Ala Trp Ala Arg Leu His Arg Leu219522002205Asn Ala Ser Ile Ala Asp Leu Gln Ser Gln Leu Arg Ser Pro Leu Gly221022152220Pro Arg His Glu Thr Ala Gln Gln Leu Glu Val Leu Glu Gln Gln Ser2225223022352240Thr Ser Leu Gly Gln Asp Ala Arg Arg Leu Gly Gly Gln Ala Ala Val224522502255Gly Thr Arg Asp Gln Ala Ser Gln Leu Leu Ala Gly Thr Glu Ala Thr226022652270Leu Gly His Ala Lys Thr Leu Leu Ala Ala Ile Arg Ala Val Asp Arg227522802285Thr Leu Ser Glu Leu Met Ser Gln Thr Gly His Leu Gly Leu Ala Asn229022952300Ala Ser Ala Pro Ser Gly Glu Gln Leu Leu Arg Thr Leu Ala Glu Val2305231023152320Glu Arg Leu Leu Trp Glu Met Arg Ala Arg Asp Leu Gly Ala Pro Gln232523302335Ala Ala Ala Glu Ala Glu Leu Ala Ala Ala Gln Arg Leu Leu Ala Arg234023452350Val Gln Glu Gln Leu Ser Ser Leu Trp Glu Glu Asn Gln Ala Leu Ala235523602365Thr Gln Thr Arg Asp Arg Leu Ala Gln His Glu Ala Gly Leu Met Asp237023752380Leu Arg Glu Ala Leu Asn Arg Ala Val Asp Ala Thr Arg Glu Ala Gln2385239023952400Glu Leu Asn Ser Arg Asn Gln Glu Arg Leu Glu Glu Ala Leu Gln Arg240524102415Lys Gln Glu Leu Ser Arg Asp Asn Ala Thr Leu Gln Ala Thr Leu His242024252430Ala Ala Arg Asp Thr Leu Ala Ser Val Phe Arg Leu Leu His Ser Leu243524402445Asp Gln Ala Lys Glu Glu Leu Glu Arg Leu Ala Ala Ser Leu Asp Gly245024552460Ala Arg Thr Pro Leu Leu Gln Arg Met Gln Thr Phe Ser Pro Ala Gly2465247024752480Ser Lys Leu Arg Leu Val Glu Ala Ala Glu Ala His Ala Gln Gln Leu248524902495Gly Gln Leu Ala Leu Asn Leu Ser Ser Ile Ile Leu Asp Val Asn Gln250025052510Asp Arg Leu Thr Gln Arg Ala Ile Glu Ala Ser Asn Ala Tyr Ser Arg251525202525Ile Leu Gln Ala Val Gln Ala Ala Glu Asp Ala Ala Gly Gln Ala Leu253025352540Gln Gln Ala Asp His Thr Trp Ala Thr Val Val Arg Gln Gly Leu Val2545255025552560Asp Arg Ala Gln Gln Leu Leu Ala Asn Ser Thr Ala Leu Glu Glu Ala256525702575Met Leu Gln Glu Gln Gln Arg Leu Gly Leu Val Trp Ala Ala Leu Gln258025852590Gly Ala Arg Thr Gln Leu Arg Asp Val Arg Ala Lys Lys Asp Gln Leu259526002605Glu Ala His Ile Gln Ala Ala Gln Ala Met Leu Ala Met Asp Thr Asp261026152620Glu Thr Ser Lys Lys Ile Ala His Ala Lys Ala Val Ala Ala Glu Ala2625263026352640Gln Asp Thr Ala Thr Arg Val Gln Ser Gln Leu Gln Ala Met Gln Glu264526502655Asn Val Glu Arg Trp Gln Gly Gln Tyr Glu Gly Leu Arg Gly Gln Asp266026652670Leu Gly Gln Ala Val Leu Asp Ala Gly His Ser Val Ser Thr Leu Glu267526802685Lys Thr Leu Pro Gln Leu Leu Ala Lys Leu Ser Ile Leu Glu Asn Arg269026952700Gly Val His Asn Ala Ser Leu Ala Leu Ser Ala Ser Ile Gly Arg Val2705271027152720Arg Glu Leu Ile Ala Gln Ala Arg Gly Ala Ala Ser Lys Val Lys Val272527302735Pro Met Lys Phe Asn Gly Arg Ser Gly Val Gln Leu Arg Thr Pro Arg274027452750Asp Leu Ala Asp Leu Ala Ala Tyr Thr Ala Leu Lys Phe Tyr Leu Gln275527602765Gly Pro Glu Pro Glu Pro Gly Gln Gly Thr Glu Asp Arg Phe Val Met277027752780Tyr Met Gly Ser Arg Gln Ala Thr Gly Asp Tyr Met Gly Val Ser Leu2785279027952800Arg Asp Lys Lys Val His Trp Val Tyr Gln Leu Gly Glu Ala Gly Pro280528102815Ala Val Leu Ser Ile Asp Glu Asp Ile Gly Glu Gln Phe Ala Ala Val282028252830Ser Leu Asp Arg Thr Leu Gln Phe Gly His Met Ser Val Thr Val Glu283528402845Arg Gln Met Ile Gln Glu Thr Lys Gly Asp Thr Val Ala Pro Gly Ala285028552860Glu Gly Leu Leu Asn Leu Arg Pro Asp Asp Phe Val Phe Tyr Val Gly2865287028752880Gly Tyr Pro Ser Thr Phe Thr Pro Pro Pro Leu Leu Arg Phe Pro Gly288528902895Tyr Arg Gly Cys Ile Glu Met Asp Thr Leu Asn Glu Glu Val Val Ser290029052910Leu Tyr Asn Phe Glu Arg Thr Phe Gln Leu Asp Thr Ala Val Asp Arg
291529202925Pro Cys Ala Arg Ser Lys Ser Thr Gly Asp Pro Trp Leu Thr Asp Gly293029352940Ser Tyr Leu Asp Gly Thr Gly Phe Ala Arg Ile Ser Phe Asp Ser Gln2945295029552960Ile Ser Thr Thr Lys Arg Phe Glu Gln Glu Leu Arg Leu Val Ser Tyr296529702975Ser Gly Va1 Leu Phe Phe Leu Lys Gln Gln Ser Gln Phe Leu Cys Leu298029852990Ala Val Gln Glu Gly Ser Leu Val Leu Leu Tyr Asp Phe Gly Ala Gly299530003005Leu Lys Lys Ala Val Pro Leu Gln Pro Pro Pro Pro Leu Thr Ser Ala301030153020Ser Lys Ala Ile Gln Val Phe Leu Leu Gly Gly Ser Arg Lys Arg Val3025303030353040Leu Val Arg Val Glu Arg Ala Thr Val Tyr Ser Val Glu Gln Asp Asn304530503055Asp Leu Glu Leu Ala Asp Ala Tyr Tyr Leu Gly Gly Val Pro Pro Asp306030653070Gln Leu Pro Pro Ser Leu Arg Arg Leu Phe Pro Thr Gly Gly Ser Val307530803085Arg Gly Cys Val Lys Gly Ile Lys Ala Leu Gly Lys Tyr Val Asp Leu309030953100Lys Arg Leu Asn Thr Thr Gly Val Ser Ala Gly Cys Thr Ala Asp Leu3105311031153120Leu Val Gly Arg Ala Met Thr Phe His Gly His Gly Phe Leu Arg Leu312531303135Ala Leu Ser Asn Val Ala Pro Leu Thr Gly Asn Val Tyr Ser Gly Phe314031453150Gly Phe His Ser Ala Gln Asp Ser Ala Leu Leu Tyr Tyr Arg Ala Ser315531603165Pro Asp Gly Leu Cys Gln Val Ser Leu Gln Gln Gly Arg Val Ser Leu317031753180Gln Leu Leu Arg Thr Glu Val Lys Thr Gln Ala Gly Phe Ala Asp Gly3185319031953200Ala Pro His Tyr Val Ala Phe Tyr Ser Asn Ala Thr Gly Val Trp Leu320532103215Tyr Val Asp Asp Gln Leu Gln Gln Met Lys Pro His Arg Gly Pro Pro322032253230Pro Glu Leu Gln Pro Gln Pro Glu Gly Pro Pro Arg Leu Leu Leu Gly323532403245Gly Leu Pro Glu Ser Gly Thr Ile Tyr Asn Phe Ser Gly Cys Ile Ser325032553260Asn Val Phe Val Gln Arg Leu Leu Gly Pro Gln Arg Val Phe Asp Leu3265327032753280Gln Gln Asn Leu Gly Ser Val Asn Val Ser Thr Gly Cys Ala Pro Ala328532903295Leu Gln Ala Gln Thr Pro Gly Leu Gly Pro Arg Gly Leu Gln Ala Thr330033053310Ala Arg Lys Ala Ser Arg Arg Ser Arg Gln Pro Ala Arg His Pro Ala331533203325Cys Met Leu Pro Pro His Leu Arg Thr Thr Arg Asp Ser Tyr Gln Phe333033353340Gly Gly Ser Leu Ser Ser His Leu Glu Phe Val Gly Ile Leu Ala Arg3345335033553360His Arg Asn Trp Pro Ser Leu Ser Met His Val Leu Pro Arg Ser Ser336533703375Arg Gly Leu Leu Leu Phe Thr Ala Arg Leu Arg Pro Gly Ser Pro Ser338033853390Leu Ala Leu Phe Leu Ser Asn Gly His Phe Val Ala Gln Met Glu Gly339534003405Leu Gly Thr Arg Leu Arg Ala Gln Ser Arg Gln Arg Ser Arg Pro Gly341034153420Arg Trp His Lys Val Ser Val Arg Trp Glu Lys Asn Arg Ile Leu Leu3425343034353440Val Thr Asp Gly Ala Arg Ala Trp Ser Gln Glu Gly Pro His Arg Gln344534503455His Gln Gly Ala Glu His Pro Gln Pro His Thr Leu Phe Val Gly Gly346034653470Leu Pro Ala Ser Ser His Ser Ser Lys Leu Pro Val Thr Val Gly Phe347534803485Ser Gly Cys Val Lys Arg Leu Arg Leu His Gly Arg Pro Leu Gly Ala349034953500Pro Thr Arg Met Ala Gly Val Thr Pro Cys Ile Leu Gly Pro Leu Glu3505351035153520Ala Gly Leu Phe Phe Pro Gly Ser Gly Gly Val Ile Thr Leu Asp Leu352535303535Pro Gly Ala Thr Leu Pro Asp Val Gly Leu Glu Leu Glu Val Arg Pro354035453550Leu Ala Val Thr Gly Leu Ile Phe His Leu Gly Gln Ala Arg Thr Pro355535603565Pro Tyr Leu Gln Leu Gln Val Thr Glu Lys Gln Val Leu Leu Arg Ala357035753580Asp Asp Gly Ala Gly Glu Phe Ser Thr Ser Val Thr Arg Pro Ser Val3585359035953600Leu Cys Asp Gly Gln Trp His Arg Leu Ala Val Met Lys Ser Gly Asn360536103615Val Leu Arg Leu Glu Val Asp Ala Gln Ser Asn His Thr Val Gly Pro362036253630Leu Leu Ala Ala Ala Ala Gly Ala Pro Ala Pro Leu Tyr Leu Gly Gly363536403645Leu Pro Glu Pro Met Ala Val Gln Pro Trp Pro Pro Ala Tyr Cys Gly365036553660Cys Met Arg Arg Leu Ala Val Asn Arg Ser Pro Val Ala Met Thr Arg3665367036753680Ser Val Glu Val His Gly Ala Val Gly Ala Ser Gly Cys Pro Ala Ala368536903695<210> 32<211> 337<212> PRT<213> 人(Homo sapiens)<400> 32Met Thr Asn Asn Ser Gly Ser Lys Ala Glu Leu Val Val Gly Gly Lys1 5 10 15Tyr Lys Leu Val Arg Lys Ile Gly Ser Gly Ser Phe Gly Asp Val Tyr20 25 30Leu Gly Ile Thr Thr Thr Asn Gly Glu Asp Val Ala Val Lys Leu Glu35 40 45Ser Gln Lys Val Lys His Pro Gln Leu Leu Tyr Glu Ser Lys Leu Tyr50 55 60Thr Ile Leu Gln Gly Gly Val Gly Ile Pro His Met His Trp Tyr Gly65 70 75 80Gln Glu Lys Asp Asn Asn Val Leu Val Met Asp Leu Leu Gly Pro Ser85 90 95Leu Glu Asp Leu Phe Asn Phe Cys Ser Arg Arg Phe Thr Met Lys Thr100 105 110Val Leu Met Leu Ala Asp Gln Met Ile Ser Arg Ile Glu Tyr Val His115 120 125Thr Lys Asn Phe Leu His Arg Asp Ile Lys Pro Asp Asn Phe Leu Met130 135 140Gly Thr Gly Arg His Cys Asn Lys Leu Phe Leu Ile Asp Phe Gly Leu145 150 155 160Ala Lys Lys Tyr Arg Asp Asn Arg Thr Arg Gln His Ile Pro Tyr Arg
165 170 175Glu Asp Lys His Leu Ile Gly Thr Val Arg Tyr Ala Ser Ile Asn Ala180 185 190His Leu Gly Ile Glu Gln Ser Arg Arg Asp Asp Met Glu Ser Leu Gly195 200 205Tyr Val Phe Met Tyr Phe Asn Arg Thr Ser Leu Pro Trp Gln Gly Leu210 215 220Arg Ala Met Thr Lys Lys Gln Lys Tyr Glu Lys Ile Ser Glu Lys Lys225 230 235 240Met Ser Thr Pro Val Glu Val Leu Cys Lys Gly Phe Pro Ala Glu Phe245 250 255Ala Met Tyr Leu Asn Tyr Cys Arg Gly Leu Arg Phe Glu Glu Val Pro260 265 270Asp Tyr Met Tyr Leu Arg Gln Leu Phe Arg Ile Leu Phe Arg Thr Leu275 280 285Asn His Gln Tyr Asp Tyr Thr Phe Asp Trp Thr Met Leu Lys Gln Lys290 295 300Ala Ala Gln Gln Ala Ala Ser Ser Ser Gly Gln Gly Gln Gln Ala Gln305 310 315 320Thr Gln Thr Gly Lys Gln Thr Glu Lys Asn Lys Asn Asn Val Lys Asp325 330 335Asn<210> 33<211> 888<212> PRT<213> 人(Homo sapiens)<400> 33Met Glu Ser Leu Leu Leu Pro Val Leu Leu Leu Leu Ala Ile Leu Trp1 5 10 15Thr Gln Ala Ala Ala Leu Ile Asn Leu Lys Tyr Ser Val Glu Glu Glu20 25 30Gln Arg Ala Gly Thr Val Ile Ala Asn Val Ala Lys Asp Ala Arg Glu35 40 45Ala Gly Phe Ala Leu Asp Pro Arg Gln Ala Ser Ala Phe Arg Val Val50 55 60Ser Asn Ser Ala Pro His Leu Val Asp Ile Asn Pro Ser Ser Gly Leu65 70 75 80Leu Val Thr Lys Gln Lys Ile Asp Arg Asp Leu Leu Cys Arg Gln Ser85 90 95Pro Lys Cys Ile Ile Ser Leu Glu Val Met Ser Ser Ser Met Glu Ile100 105 110Cys Val Ile Lys Val Glu Ile Lys Asp Leu Asn Asp Asn Ala Pro Ser115 120 125Phe Pro Ala Ala Gln Ile Glu Leu Glu Ile Ser Glu Ala Ala Ser Pro130 135 140Gly Thr Arg Ile Pro Leu Asp Ser Ala Tyr Asp Pro Asp Ser Gly Ser145 150 155 160Phe Gly Val Gln Thr Tyr Glu Leu Thr Pro Asn Glu Leu Phe Gly Leu165 170 175Glu Ile Lys Thr Arg Gly Asp Gly Ser Arg Phe Ala Glu Leu Val Val180 185 190Glu Lys Ser Leu Asp Arg Glu Thr Gln Ser His Tyr Ser Phe Arg Ile195 200 205Thr Ala Leu Asp Gly Gly Asp Pro Pro Arg Leu Gly Thr Val Gly Leu210 215 220Ser Ile Lys Val Thr Asp Ser Asn Asp Asn Asn Pro Val Phe Ser Glu225 230 235 240Ser Thr Tyr Ala Val Ser Val Pro Glu Asn Ser Pro Pro Asn Thr Pro
245 250 255Val Ile Arg Leu Asn Ala Ser Asp Pro Asp Glu Gly Thr Asn Gly Gln260 265 270Val Val Tyr Ser Phe Tyr Gly Tyr Val Asn Asp Arg Thr Arg Glu Leu275 280 285Phe Gln Ile Asp Pro His Ser Gly Leu Val Thr Val Thr Gly Ala Leu290 295 300Asp Tyr Glu Glu Gly His Val Tyr Glu Leu Asp Val Gln Ala Lys Asp305 310 315 320Leu Gly Pro Asn Ser Ile Pro Ala His Cys Lys Val Thr Val Ser Val325 330 335Leu Asp Thr Asn Asp Asn Pro Pro Val Ile Asn Leu Leu Ser Val Asn340 345 350Ser Glu Leu Val Glu Val Ser Glu Ser Ala Pro Pro Gly Tyr Val Ile355 360 365Ala Leu Val Arg Val Ser Asp Arg Asp Ser Gly Leu Asn Gly Arg Val370 375 380Gln Cys Arg Leu Leu Gly Asn Val Pro Phe Arg Leu Gln Glu Tyr Glu385 390 395 400Ser Phe Ser Thr Ile Leu Val Asp Gly Arg Leu Asp Arg Glu Gln His405 410 415Asp Gln Tyr Asn Leu Thr Ile Gln Ala Arg Asp Gly Gly Val Pro Met420 425 430Leu Gln Ser Ala Lys Ser Phe Thr Val Leu Ile Thr Asp Glu Asn Asp435 440 445Asn His Pro His Phe Ser Lys Pro Tyr Tyr Gln Val Ile Val Gln Glu450 455 460Asn Asn Thr Pro Gly Ala Tyr Leu Leu Ser Val Ser Ala Arg Asp Pro465 470 475 480Asp Leu Gly Leu Asn Gly Ser Val Ser Tyr Gln Ile Val Pro Ser Gln485 490 495Val Arg Asp Met Pro Val Phe Thr Tyr Val Ser Ile Asn Pro Asn Ser500 505 510Gly Asp Ile Tyr Ala Leu Arg Ser Phe Asn His Glu Gln Thr Lys Ala515 520 525Phe Glu Phe Lys Val Leu Ala Lys Asp Gly Gly Leu Pro Ser Leu Gln530 535 540Ser Asn Ala Thr Val Arg Val Ile Ile Leu Asp Val Asn Asp Asn Thr545 550 555 560Pro Val Ile Thr Ala Pro Pro Leu Ile Asn Gly Thr Ala Glu Val Tyr565 570 575Ile Pro Arg Asn Ser Gly Ile Gly Tyr Leu Val Thr Val Val Lys Ala580 585 590Glu Asp Tyr Asp Glu Gly Glu Asn Gly Arg Val Thr Tyr Asp Met Thr595 600 605Glu Gly Asp Arg Gly Phe Phe Glu Ile Asp Gln Val Asn Gly Glu Val610 615 620Arg Thr Thr Arg Thr Phe Gly Glu Ser Ser Lys Ser Ser Tyr Glu Leu625 630 635 640Ile Val Val Ala His Asp His Gly Lys Thr Ser Leu Ser Ala Ser Ala645 650 655Leu Val Leu Ile Tyr Leu Ser Pro Ala Leu Asp Ala Gln Glu Ser Met660 665 670Gly Ser Val Asn Leu Ser Leu Ile Phe Ile Ile Ala Leu Gly Ser Ile675 680 685Ala Gly Ile Leu Phe Val Thr Met Ile Phe Val Ala Ile Lys Cys Lys690 695 700Arg Asp Asn Lys Glu Ile Arg Thr Tyr Asn Cys Ser Asn Cys Leu Thr705 710 715 720Ile Thr Cys Leu Leu Gly Cys Phe Ile Lys Gly Gln Asn Ser Lys Cys725 730 735Leu His Cys Ile Ser Val Ser Pro Ile Ser Glu Glu Gln Asp Lys Lys740 745 750Thr Glu Glu Lys Val Ser Leu Arg Gly Lys Arg Ile Ala Glu Tyr Ser755 760765Tyr Gly His Gln Lys Lys Ser Ser Lys Lys Lys Lys Ile Ser Lys Asn770 775 780Asp Ile Arg Leu Val Pro Arg Asp Val Glu Glu Thr Asp Lys Met Asn785 790 795 800Val Val Ser Cys Ser Ser Leu Thr Ser Ser Leu Asn Tyr Phe Asp Tyr805 810 815His Gln Gln Thr Leu Pro Leu Gly Cys Arg Arg Ser Glu Ser Thr Phe820 825 830Leu Asn Val Glu Asn Gln Asn Thr Arg Asn Thr Ser Ala Asn His Ile835 840 845Tyr His His Ser Phe Asn Ser Gln Gly Pro Gln Gln Pro Asp Leu Ile850 855 860Ile Asn Gly Val Pro Leu Pro Glu Val Ser Ala Ala Lys Trp Leu Cys865 870 875 880Glu Val Leu Pro Gly Leu Leu Leu885<210> 34<211> 855<212> PRT<213> 人(Homo sapiens)<400> 34Met Glu Ser Leu Leu Leu Pro Val Leu Leu Leu Leu Ala Ile Leu Trp1 5 10 15Thr Gln Ala Ala Ala Leu Ile Asn Leu Lys Tyr Ser Val Glu Glu Glu20 25 30Gln Arg Ala Gly Thr Val Ile Ala Asn Val Ala Lys Asp Ala Arg Glu35 40 45Ala Gly Phe Ala Leu Asp Pro Arg Gln Ala Ser Ala Phe Arg Val Val50 55 60Ser Asn Ser Ala Pro His Leu Val Asp Ile Asn Pro Ser Ser Gly Leu65 70 75 80Leu Val Thr Lys Gln Lys Ile Asp Arg Asp Leu Leu Cys Arg Gln Ser85 90 95Pro Lys Cys Ile Ile Ser Leu Glu Val Met Ser Ser Ser Met Glu Ile100 105 110Cys Val Ile Lys Val Glu Ile Lys Asp Leu Asn Asp Asn Ala Pro Ser115 120 125Phe Pro Ala Ala Gln Ile Glu Leu Glu Ile Ser Glu Ala Ala Ser Pro130 135 140Gly Thr Arg Ile Pro Leu Asp Ser Ala Tyr Asp Pro Asp Ser Gly Ser145 150 155 160Phe Gly Val Gln Thr Tyr Glu Leu Thr Pro Asn Glu Leu Phe Gly Leu165 170 175Glu Ile Lys Thr Arg Gly Asp Gly Ser Arg Phe Ala Glu Leu Val Val180 185 190Glu Lys Ser Leu Asp Arg Glu Thr Gln Ser His Tyr Ser Phe Arg Ile195 200 205Thr Ala Leu Asp Gly Gly Asp Pro Pro Arg Leu Gly Thr Val Gly Leu210 215 220Ser Ile Lys Val Thr Asp Ser Asn Asp Asn Asn Pro Val Phe Ser Glu225 230 235 240Ser Thr Tyr Ala Val Ser Val Pro Glu Asn Ser Pro Pro Asn Thr Pro245 250 255Val Ile Arg Leu Asn Ala Ser Asp Pro Asp Glu Gly Thr Asn Gly Gln260 265 270Val Val Tyr Ser Phe Tyr Gly Tyr Val Asn Asp Arg Thr Arg Glu Leu275 280 285Phe Gln Ile Asp Pro His Ser Gly Leu Val Thr Val Thr Gly Ala Leu
290 295 300Asp Tyr Glu Glu Gly His Val Tyr Glu Leu Asp Val Gln Ala Lys Asp305 310 315 320Leu Gly Pro Asn Ser Ile Pro Ala His Cys Lys Val Thr Val Ser Val325 330 335Leu Asp Thr Asn Asp Asn Pro Pro Val Ile Asn Leu Leu Ser Val Asn340 345 350Ser Glu Leu Val Glu Val Ser Glu Ser Ala Pro Pro Gly Tyr Val Ile355 360 365Ala Leu Val Arg Val Ser Asp Arg Asp Ser Gly Leu Asn Gly Arg Val370 375 380Gln Cys Arg Leu Leu Gly Asn Val Pro Phe Arg Leu Gln Glu Tyr Glu385 390 395 400Ser Phe Ser Thr Ile Leu Val Asp Gly Arg Leu Asp Arg Glu Gln His405 410 415Asp Gln Tyr Asn Leu Thr Ile Gln Ala Arg Asp Gly Gly Val Pro Met420 425 430Leu Gln Ser Ala Lys Ser Phe Thr Val Leu Ile Thr Asp Glu Asn Asp435 440 445Asn His Pro His Phe Ser Lys Pro Tyr Tyr Gln Val Ile Val Gln Glu450 455 460Asn Asn Thr Pro Gly Ala Tyr Leu Leu Ser Val Ser Ala Arg Asp Pro465 470 475 480Asp Leu Gly Leu Asn Gly Ser Val Ser Tyr Gln Ile Val Pro Ser Gln485 490 495Val Arg Asp Met Pro Val Phe Thr Tyr Val Ser Ile Ash Pro Asn Ser500 505 510Gly Asp Ile Tyr Ala Leu Arg Ser Phe Asn His Glu Gln Thr Lys Ala515 520 525Phe Glu Phe Lys Val Leu Ala Lys Asp Gly Gly Leu Pro Ser Leu Gln530 535 540Ser Asn Ala Thr Val Arg Val Ile Ile Leu Asp Val Asn Asp Asn Thr545 550 555 560Pro Val Ile Thr Ala Pro Pro Leu Ile Asn Gly Thr Ala Glu Val Tyr565 570 575Ile Pro Arg Asn Ser Gly Ile Gly Tyr Leu Val Thr Val Val Lys Ala580 585 590Glu Asp Tyr Asp Glu Gly Glu Asn Gly Arg Val Thr Tyr Asp Met Thr595 600 605Glu Gly Asp Arg Gly Phe Phe Glu Ile Asp Gln Val Asn Gly Glu Val610 615 620Arg Thr Thr Arg Thr Phe Gly Glu Ser Ser Lys Ser Ser Tyr Glu Leu625 630 635 640Ile Val Val Ala His Asp His Gly Lys Thr Ser Leu Ser Ala Ser Ala645 650 655Leu Val Leu Ile Tyr Leu Ser Pro Ala Leu Asp Ala Gln Glu Ser Met660 665 670Gly Ser Val Asn Leu Ser Leu Ile Phe Ile Ile Ala Leu Gly Ser Ile675 680 685Ala Gly Ile Leu Phe Val Thr Met Ile Phe Val Ala Ile Lys Cys Lys690 695 700Arg Asp Asn Lys Glu Ile Arg Thr Tyr Asn Cys Arg Ile Ala Glu Tyr705 710 715 720Ser Tyr Gly His Gln Lys Lys Ser Ser Lys Lys Lys Lys Ile Ser Lys725 730 735Asn Asp Ile Arg Leu Val Pro Arg Asp Val Glu Glu Thr Asp Lys Met740 745 750Asn Val Val Ser Cys Ser Ser Leu Thr Ser Ser Leu Asn Tyr Phe Asp755 760 765Tyr His Gln Gln Thr Leu Pro Leu Gly Cys Arg Arg Ser Glu Ser Thr770 775 780Phe Leu Asn Val Glu Asn Gln Asn Thr Arg Asn Thr Ser Ala Asn His785 790 795 800Ile Tyr His His Ser Phe Asn Ser Gln Gly Pro Gln Gln Pro Asp Leu805 810 815Ile Ile Asn Gly Val Pro Leu Pro Glu Thr Glu Asn Tyr Ser Phe Asp820 825 830Ser Asn Tyr Val Asn Ser Arg Ala His Leu Ile Lys Arg Tyr Val Gly835 840 845Leu Leu Ala Tyr Cys Cys Asn850 855<210> 35<211> 329<212> PRT<213> 人(Homo sapiens)<400> 35Met Val Thr Lys Ala Phe Val Leu Leu Ala Ile Phe Ala Glu Ala Ser1 5 10 15Ala Lys Ser Cys Ala Pro Asn Lys Ala Asp Val Ile Leu Val Phe Cys20 25 30Tyr Pro Lys Thr Ile Ile Thr Lys Ile Pro Glu Cys Pro Tyr Gly Trp35 40 45Glu Val His Gln Leu Ala Leu Gly Gly Leu Cys Tyr Asn Gly Val His50 55 60Glu Gly Gly Tyr Tyr Gln Phe Val Ile Pro Asp Leu Ser Pro Lys Asn65 70 75 80Lys Ser Tyr Cys Gly Thr Gln Ser Glu Tyr Lys Pro Pro Ile Tyr His85 90 95Phe Tyr Ser His Ile Val Ser Asn Asp Thr Thr Val Ile Val Lys Asn100 105 110Gln Pro Val Asn Tyr Ser Phe Ser Cys Thr Tyr His Ser Thr Tyr Leu115 120 125Val Asn Gln Ala Ala Phe Asp Gln Arg Val Ala Thr Val His Val Lys130 135 140Asn Gly Ser Met Gly Thr Phe Glu Ser Gln Leu Ser Leu Asn Phe Tyr145 150 155 160Thr Asn Ala Lys Phe Ser Ile Lys Lys Glu Ala Pro Phe Val Leu Glu165 170 175Ala Ser Glu Ile Gly Ser Asp Leu Phe Ala Gly Val Glu Ala Lys Gly180 185 190Leu Ser Ile Arg Phe Lys Val Val Leu Asn Ser Cys Trp Ala Thr Pro195 200 205Ser Ala Asp Phe Met Tyr Pro Leu Gln Trp Gln Leu Ile Asn Lys Gly210 215 220Cys Pro Thr Asp Glu Thr Val Leu Val His Glu Asn Gly Arg Asp His225 230 235 240Arg Ala Thr Phe Gln Phe Asn Ala Phe Arg Phe Gln Asn Ile Pro Lys245 250 255Leu Ser Lys Val Trp Leu His Cys Glu Thr Phe Ile Cys Asp Ser Glu260 265 270Lys Leu Ser Cys Pro Val Thr Cys Asp Lys Arg Lys Arg Leu Leu Arg275 280 285Asp Gln Thr Gly Gly Val Leu Val Val Glu Leu Ser Leu Arg Ser Arg290 295 300Gly Phe Ser Ser Leu Tyr Ser Phe Ser Asp Val Leu His His Leu Ile305 310 315 320Met Met Leu Gly Ile Cys Ala Val Leu325<210> 36<211> 232<212> PRT<213> 人(Homo sapiens)<400> 36Met Leu Tyr Thr Arg Lys Asn Leu Thr Cys Ala Gln Thr Ile Asn Ser1 5 10 15Ser Ala Phe Gly Asn Leu Asn Val Thr Lys Lys Thr Thr Phe Ile Val20 25 30His Gly Phe Arg Pro Thr Gly Ser Pro Pro Val Trp Met Asp Asp Leu35 40 45Val Lys Gly Leu Leu Ser Val Glu Asp Met Asn Val Val Val Val Asp50 55 60Trp Asn Arg Gly Ala Thr Thr Leu Ile Tyr Thr His Ala Ser Ser Lys65 70 75 80Thr Arg Lys Val Ala Met Val Leu Lys Glu Phe Ile Asp Gln Met Leu85 90 95Ala Glu Gly Ala Ser Leu Asp Asp Ile Tyr Met Ile Gly Val Ser Leu100 105 110Gly Ala His Ile Ser Gly Phe Val Gly Glu Met Tyr Asp Gly Trp Leu115 120 125Gly Arg Ile Thr Gly Leu Asp Pro Ala Gly Pro Leu Phe Asn Gly Lys130 135 140Pro His Gln Asp Arg Leu Asp Pro Ser Asp Ala Gln Phe Val Asp Val145 150 155 160Ile His Ser Asp Thr Asp Gly Asn Ala Pro Phe Leu Val Ala Leu Gly165 170 175Tyr Lys Glu Pro Leu Gly Asn Ile Asp Phe Tyr Pro Asn Gly Gly Leu180 185 190Asp Gln Pro Gly Cys Pro Lys Thr Ile Leu Gly Gly Asn Val Lys Glu195 200 205Met Ile Gln Ala Ser Tyr Ile Phe Phe Leu Lys Asn Asp Ser Met Asp210 215 220Leu Ser Ser Pro Lys Glu Val Glu225 230<210> 37<211> 452<212> PRT<213> 人(Homo sapiens)<400> 37Met Leu Arg Phe Tyr Leu Phe Ile Ser Leu Leu Cys Leu Ser Arg Ser1 5 10 15Asp Ala Glu Glu Thr Cys Pro Ser Phe Thr Arg Leu Ser Phe His Ser20 25 30Ala Val Val Gly Thr Gly Leu Asn Val Arg Leu Met Leu Tyr Thr Arg35 40 45Lys Asn Leu Thr Cys Ala Gln Thr Ile Asn Ser Ser Ala Phe Gly Asn50 55 60Leu Asn Val Thr Lys Lys Thr Thr Phe Ile Val His Gly Phe Arg Pro65 70 75 80Thr Gly Ser Pro Pro Val Trp Met Asp Asp Leu Val Lys Gly Leu Leu85 90 95Ser Val Glu Asp Met Asn Val Val Val Val Asp Trp Asn Arg Gly Ala100 105 110Thr Thr Leu Ile Tyr Thr His Ala Ser Ser Lys Thr Arg Lys Val Ala115 120 125Met Val Leu Lys Glu Phe Ile Asp Gln Met Leu Ala Glu Gly Ala Ser130 135 140Leu Asp Asp Ile Tyr Met Ile Gly Val Ser Leu Gly Ala His Ile Ser145 150 155 160Gly Phe Val Gly Glu Met Tyr Asp Gly Trp Leu Gly Arg Ile Thr Gly165 170 175Leu Asp Pro Ala Gly Pro Leu Phe Asn Gly Lys Pro His Gln Asp Arg180 185 190Leu Asp Pro Ser Asp Ala Gln Phe Val Asp Val Ile His Ser Asp Thr195 200 205Asp Ala Leu Gly Tyr Lys Glu Pro Leu Gly Asn Ile Asp Phe Tyr Pro210 215 220Asn Gly Gly Leu Asp Gln Pro Gly Cys Pro Lys Thr Ile Leu Gly Gly225 230 235 240Phe Gln Tyr Phe Lys Cys Asp His Gln Arg Ser Val Tyr Leu Tyr Leu245 250 255Ser Ser Leu Arg Glu Ser Cys Thr Ile Thr Ala Tyr Pro Cys Asp Ser260 265 270Tyr Gln Asp Tyr Arg Asn Gly Lys Cys Val Ser Cys Gly Thr Ser Gln275 280 285Lys Glu Ser Cys Pro Leu Leu Gly Tyr Tyr Ala Asp Asn Trp Lys Asp290 295 300His Leu Arg Gly Lys Asp Pro Pro Met Thr Lys Ala Phe Phe Asp Thr305 310 315 320Ala Glu Glu Ser Pro Phe Cys Met Tyr His Tyr Phe Val Asp Ile Ile325 330 335Thr Trp Asp Lys Asn Val Arg Arg Gly Asp Ile Thr Ile Lys Leu Arg340 345 350Asp Lys Ala Gly Asn Thr His Arg Ser Lys Ile Ile Ser Asn Glu Pro355 360 365Thr Thr Phe Gln Lys Tyr His Gln Val Ser Leu Leu Ala Arg Phe Asn370 375 380Gln Asp Leu Asp Lys Val Ala Ala Ile Ser Leu Met Phe Ser Thr Gly385 390 395 400Ser Leu Ile Gly Pro Arg Tyr Lys Leu Arg Ile Leu Arg Met Lys Leu405 410 415Arg Ser Leu Ala His Pro Glu Arg Pro Gln Leu Cys Arg Tyr Asp Leu420 425 430Val Leu Met Glu Asn Val Glu Thr Val Phe Gln Pro Ile Leu Cys Pro435 440 445Glu Leu Gln Leu450<210> 38<211> 450<212> PRT<213> 人(Homo sapiens)<400> 38Met Gly Leu Arg Ser His His Leu Ser Leu Gly Leu Leu Leu Leu Phe1 5 10 15Leu Leu Pro Ala Glu Cys Leu Gly Ala Glu Gly Arg Leu Ala Leu Lys20 25 30Leu Phe Arg Asp Leu Phe Ala Asn Tyr Thr Ser Ala Leu Arg Pro Val35 40 45Ala Asp Thr Asp Gln Thr Leu Asn Val Thr Leu Glu Val Thr Leu Ser50 55 60Gln Ile Ile Asp Met Asp Glu Arg Asn Gln Val Leu Thr Leu Tyr Leu65 70 75 80Trp Ile Arg Gln Glu Trp Thr Asp Ala Tyr Leu Arg Trp Asp Pro Asn85 90 95Ala Tyr Gly Gly Leu Asp Ala Ile Arg Ile Pro Ser Ser Leu Val Trp100 105 110Arg Pro Asp Ile Val Leu Tyr Asn Lys Ala Asp Ala Gln Pro Pro Gly115 120 125Ser Ala Ser Thr Asn Val Val Leu Arg His Asp Gly Ala Val Arg Trp130 135 140Asp Ala Pro Ala Ile Thr Arg Ser Ser Cys Arg Val Asp Val Ala Ala145 150 155 160Phe Pro Phe Asp Ala Gln His Cys Gly Leu Thr Phe Gly Ser Trp Thr165 170 175His Gly Gly His Gln Leu Asp Val Arg Pro Arg Gly Ala Ala Ala Ser180 185 190Leu Ala Asp Phe Val Glu Asn Val Glu Trp Arg Val Leu Gly Met Pro195 200 205Ala Arg Arg Arg Val Leu Thr Tyr Gly Cys Cys Ser Glu Pro Tyr Pro210 215 220Asp Val Thr Phe Thr Leu Leu Leu Arg Arg Arg Ala Ala Ala Tyr Val225 230 235 240Cys Asn Leu Leu Leu Pro Cys Val Leu Ile Ser Leu Leu Ala Pro Leu245 250 255Ala Phe His Leu Pro Ala Asp Ser Gly Glu Lys Val Ser Leu Gly Val260 265 270Thr Val Leu Leu Ala Leu Thr Val Phe Gln Leu Leu Leu Ala Glu Ser275 280 285Met Pro Pro Ala Glu Ser Val Pro Leu Ile Gly Lys Tyr Tyr Met Ala290 295 300Thr Met Thr Met Val Thr Phe Ser Thr Ala Leu Thr Ile Leu Ile Mer305 310 315 320Asn Leu His Tyr Cys Gly Pro Ser Val Arg Pro Val Pro Ala Trp Ala325 330 335Arg Ala Leu Leu Leu Gly His Leu Ala Arg Gly Leu Cys Val Arg Glu340 345 350Arg Gly Glu Pro Cys Gly Gln Ser Arg Pro Pro Glu Leu Ser Pro Ser355 360 365Pro Gln Ser Pro Glu Gly Gly Ala Gly Pro Pro Ala Gly Pro Cys His370 375 380Glu Pro Arg Cys Leu Cys Arg Gln Glu Ala Leu Leu His His Val Ala385 390 395 400Thr Ile Ala Asn Thr Phe Arg Ser His Arg Ala Ala Gln Arg Cys His405 410 415Glu Asp Trp Lys Arg Leu Ala Arg Val Met Asp Arg Phe Phe Leu Ala420 425 430Ile Phe Phe Ser Met Ala Leu Val Met Ser Leu Leu Val Leu Val Gln435 440 445Ala Leu450<210> 39<211> 255<212> PRT<213> 人(Homo sapiens)<400> 39Met Val Lys Gly Glu Lys Gly Pro Lys Gly Lys Lys Ile Thr Leu Lys1 5 10 15Val Ala Arg Asn Cys Ile Lys Ile Thr Phe Asp Gly Lys Lys Arg Leu20 25 30Asp Leu Ser Lys Met Gly Ile Thr Thr Phe Pro Lys Cys Ile Leu Arg35 40 45Leu Ser Asp Met Asp Glu Leu Asp Leu Ser Arg Asn Leu Ile Arg Lys50 55 60Ile Pro Asp Ser Ile Ser Lys Phe Gln Asn Leu Arg Trp Leu Asp Leu65 70 75 80His Ser Asn Tyr Ile Asp Lys Leu Pro Glu Ser Ile Gly Gln Met Thr85 90 95Ser Leu Leu Tyr Leu Asn Val Ser Asn Asn Arg Leu Thr Ser Asn Gly100 105 110Leu Pro Val Glu Leu Lys Gln Leu Lys Asn Ile Arg Ala Val Asn Leu
115 120 125Gly Leu Asn His Leu Asp Ser Val Pro Thr Thr Leu Gly Ala Leu Lys130 135 140Glu Leu His Glu Val Gly Leu His Asp Asn Leu Leu Asn Asn Ile Pro145 150 155 160Val Ser Ile Ser Lys Leu Pro Lys Leu Lys Lys Leu Asn Ile Lys Arg165 170 175Asn Pro Phe Pro Lys Pro Gly Glu Ser Glu Ile Phe Ile Asp Ser Ile180 185 190Arg Arg Leu Glu Asn Leu Tyr Val Val Glu Glu Lys Asp Leu Cys Ala195 200 205Ala Cys Leu Arg Lys Cys Gln Asn Ala Arg Asp Asn Leu Asn Arg Ile210 215 220Lys Asn Met Ala Thr Thr Thr Pro Arg Lys Thr Ile Phe Pro Asn Leu225 230 235 240Ile Ser Pro Asn Ser Met Ala Lys Asp Ser Trp Glu Asp Trp Arg245 250 255<210> 40<211> 214<212> PRT<213> 人(Homo sapiens)<400> 40Met Gln Ala Gly Thr Gln Ser Thr His Glu Ser Leu Lys Pro Gln Arg1 5 10 15Val Gln Phe Gln Ser Arg Asn Phe His Asn Ile Leu Gln Trp Gln Pro20 25 30Gly Arg Ala Leu Thr Gly Asn Ser Ser Val Tyr Phe Val Gln Tyr Lys35 40 45Ile Tyr Gly Gln Arg Gln Trp Lys Asn Lys Glu Asp Cys Trp Gly Thr50 55 60Gln Glu Leu Ser Cys Asp Leu Thr Ser Glu Thr Ser Asp Ile Gln Glu65 70 75 80Pro Tyr Tyr Gly Arg Val Arg Ala Ala Ser Ala Gly Ser Tyr Ser Glu85 90 95Trp Ser Met Thr Pro Arg Phe Thr Pro Trp Trp Glu Thr Lys Ile Asp100 105 110Pro Pro Val Met Asn Ile Thr Gln Val Asn Gly Ser Leu Leu Val Ile115 120 125Leu His Ala Pro Asn Leu Pro Tyr Arg Tyr Gln Lys Glu Lys Asn Val130 135 140Ser Ile Glu Asp Tyr Tyr Glu Leu Leu Tyr Arg Val Phe Ile Ile Asn145 150 155 160Asn Ser Leu Glu Lys Glu Gln Lys Val Tyr Glu Gly Ala His Arg Ala165 170 175Val Glu Ile Glu Ala Leu Thr Pro His Ser Ser Tyr Cys Val Val Ala180 185 190Glu Ile Tyr Gln Pro Met Leu Asp Arg Arg Ser Gln Arg Ser Glu Glu195 200 205Arg Cys Val Glu Ile Pro210<210> 41<211> 231<212> PRT<213> 人(Homo sapiens)<400> 41Met Met Pro Lys His Cys Phe Leu Gly Phe Leu Ile Ser Phe Phe Leu1 5 10 15Thr Gly Val Ala Gly Thr Gln Ser Thr His Glu Ser Leu Lys Pro Gln20 25 30Arg Val Gln Phe Gln Ser Arg Asn Phe His Asn Ile Leu Gln Trp Gln35 40 45Pro Gly Arg Ala Leu Thr Gly Asn Ser Ser Val Tyr Phe Val Gln Tyr50 55 60Lys Ile Tyr Gly Gln Arg Gln Trp Lys Asn Lys Glu Asp Cys Trp Gly65 70 75 80Thr Gln Glu Leu Ser Cys Asp Leu Thr Ser Glu Thr Ser Asp Ile Gln85 90 95Glu Pro Tyr Tyr Gly Arg Val Arg Ala Ala Ser Ala Gly Ser Tyr Ser100 105 110Glu Trp Ser Met Thr Pro Arg Phe Thr Pro Trp Trp Glu Thr Lys Ile115 120 125Asp Pro Pro Val Met Asn Ile Thr Gln Val Asn Gly Ser Leu Leu Val130 135 140Ile Leu His Ala Pro Asn Leu Pro Tyr Arg Tyr Gln Lys Glu Lys Asn145 150 155 160Val Ser Ile Glu Asp Tyr Tyr Glu Leu Leu Tyr Arg Val Phe Ile Ile165 170 175Asn Asn Ser Leu Glu Lys Glu Gln Lys Val Tyr Glu Gly Ala His Arg180 185 190Ala Val Glu Ile Glu Ala Leu Thr Pro His Ser Ser Tyr Cys Val Val195 200 205Ala Glu Ile Tyr Gln Pro Met Leu Asp Arg Arg Ser Gln Arg Ser Glu210 215 220Glu Arg Cys Val Glu Ile Pro225 230<210> 42<211> 263<212> PRT<213> 人(Homo sapiens)<400> 42Met Met Pro Lys His Cys Phe Leu Gly Phe Leu Ile Ser Phe Phe Leu1 5 10 15Thr Gly Val Ala Gly Thr Gln Ser Thr His Glu Ser Leu Lys Pro Gln20 25 30Arg Val Gln Phe Gln Ser Arg Asn Phe His Asn Ile Leu Gln Trp Gln35 40 45Pro Gly Arg Ala Leu Thr Gly Asn Ser Ser Val Tyr Phe Val Gln Tyr50 55 60Lys Ile Met Phe Ser Cys Ser Met Lys Ser Ser His Gln Lys Pro Ser65 70 75 80Gly Cys Trp Gln His Ile Ser Cys Asn Phe Pro Gly Cys Arg Thr Leu85 90 95Ala Lys Tyr Gly Gln Arg Gln Trp Lys Asn Lys Glu Asp Cys Trp Gly100 105 110Thr Gln Glu Leu Ser Cys Asp Leu Thr Ser Glu Thr Ser Asp Ile Gln115 120 125Glu Pro Tyr Tyr Gly Arg Val Arg Ala Ala Ser Ala Gly Ser Tyr Ser130 135 140Glu Trp Ser Met Thr Pro Arg Phe Thr Pro Trp Trp Glu Thr Lys Ile145 150 155 160Asp Pro Pro Val Met Asn Ile Thr Gln Val Asn Gly Ser Leu Leu Val165 170 175Ile Leu His Ala Pro Asn Leu Pro Tyr Arg Tyr Gln Lys Glu Lys Asn180 185 190Val Ser Ile Glu Asp Tyr Tyr Glu Leu Leu Tyr Arg Val Phe Ile Ile195 200 205Asn Asn Ser Leu Glu Lys Glu Gln Lys Val Tyr Glu Gly Ala His Arg
210 215 220Ala Val Glu Ile Glu Ala Leu Thr Pro His Ser Ser Tyr Cys Val Val225 230 235 240Ala Glu Ile Tyr Gln Pro Met Leu Asp Arg Arg Ser Gln Arg Ser Glu245 250 255Glu Arg Cys Val Glu Ile Pro260<210> 43<211> 259<212> PRT<213> 人(Homo sapiens)<400> 43Met Tyr Val Leu Ser Pro Val Glu Phe Ile Ile Leu Gln Leu Leu Phe1 5 10 15Ile Gln Ala Ile Ser Ser Ser Leu Lys Gly Phe Leu Ser Ala Met Arg20 25 30Leu Ala His Arg Gly Cys Asn Val Asp Thr Pro Val Ser Thr Leu Thr35 40 45Pro Val Lys Thr Ser Glu Phe Glu Asn Phe Lys Thr Lys Met Val Ile50 55 60Thr Ser Lys Lys Asp Tyr Pro Leu Ser Lys Asn Phe Pro Tyr Ser Leu65 70 75 80Glu His Leu Gln Thr Ser Tyr Cys Gly Leu Val Arg Val Asp Met Arg85 90 95Met Leu Cys Leu Lys Ser Leu Arg Lys Leu Asp Leu Ser His Asn His100 105 110Ile Lys Lys Leu Pro Ala Thr Ile Gly Asp Leu Ile His Leu Gln Glu115 120 125Leu Asn Leu Asn Asp Asn His Leu Glu Ser Phe Ser Val Ala Leu Cys130 135 140His Ser Thr Leu Gln Lys Ser Leu Arg Ser Leu Asp Leu Ser Lys Asn145 150 155 160Lys Ile Lys Ala Leu Pro Val Gln Phe Cys Gln Leu Gln Glu Leu Lys165 170 175Asn Leu Lys Leu Asp Asp Asn Glu Leu Ile Gln Phe Pro Cys Lys Ile180 185 190Gly Gln Leu Ile Asn Leu Arg Phe Leu Ser Ala Ala Arg Asn Lys Leu195 200 205Pro Phe Leu Pro Ser Glu Phe Arg Asn Leu Ser Leu Glu Tyr Leu Asp210 215 220Leu Phe Gly Asn Thr Phe Glu Gln Pro Lys Val Leu Pro Val Ile Lys225 230 235 240Leu Gln Ala Pro Leu Thr Leu Leu Glu Ser Ser Ala Arg Thr Ile Leu245 250 255His Asn Arg<210> 44<211> 416<212> PRT<213> 人(Homo sapiens)<400> 44Met Lys Leu His Cys Glu Val Glu Val Ile Ser Arg His Leu Pro Ala1 5 10 15Leu Gly Leu Arg Asn Arg Gly Lys Gly Val Arg Ala Val Leu Ser Leu20 25 30Cys Gln Gln Thr Ser Arg Ser Gln Pro Pro Val Arg Ala Phe Leu Leu35 40 45Ile Ser Thr Leu Lys Asp Lys Arg Gly Thr Arg Tyr Glu Leu Arg Glu50 55 60Asn Ile Glu Gln Phe Phe Thr Lys Phe Val Asp Glu Gly Lys Ala Thr65 70 75 80Val Arg Leu Lys Glu Pro Pro Val Asp Ile Cys Leu Ser Lys Ala Ile85 90 95Ser Ser Ser Leu Lys Gly Phe Leu Ser Ala Met Arg Leu Ala His Arg100 105 110Gly Cys Asn Val Asp Thr Pro Val Ser Thr Leu Thr Pro Val Lys Thr115 120 125Ser Glu Phe Glu Asn Phe Lys Thr Lys Met Val Ile Thr Ser Lys Lys130 135 140Asp Tyr Pro Leu Ser Lys Asn Phe Pro Tyr Ser Leu Glu His Leu Gln145 150 155 160Thr Ser Tyr Cys Gly Leu Val Arg Val Asp Met Arg Met Leu Cys Leu165 170 175Lys Ser Leu Arg Lys Leu Asp Leu Ser His Asn His Ile Lys Lys Leu180 185 190Pro Ala Thr Ile Gly Asp Leu Ile His Leu Gln Glu Leu Asn Leu Asn195 200 205Asp Asn His Leu Glu Ser Phe Ser Val Ala Leu Cys His Ser Thr Leu210 215 220Gln Lys Ser Leu Arg Ser Leu Asp Leu Ser Lys Asn Lys Ile Lys Ala225 230 235 240Leu Pro Val Gln Phe Cys Gln Leu Gln Glu Leu Lys Asn Leu Lys Leu245 250 255Asp Asp Asn Glu Leu Ile Gln Phe Pro Cys Lys Ile Gly Gln Leu Ile260 265 270Asn Leu Arg Phe Leu Ser Ala Ala Arg Asn Lys Leu Pro Phe Leu Pro275 280 285Ser Glu Phe Arg Asn Leu Ser Leu Glu Tyr Leu Asp Leu Phe Gly Asn290 295 300Thr Phe Glu Gln Pro Lys Val Leu Pro Val Ile Lys Leu Gln Ala Pro305 310 315 320Leu Thr Leu Leu Glu Ser Ser Ala Arg Thr Ile Leu His Asn Arg Asn325 330 335Arg Ile Pro Tyr Gly Ser His Ile Ile Pro Phe His Leu Cys Gln Asp340 345 350Leu Asp Thr Ala Lys Ile Cys Val Cys Gly Arg Phe Cys Leu Asn Ser355 360 365Phe Ile Gln Gly Thr Thr Thr Met Asn Leu His Ser Val Ala His Thr370 375 380Val Val Leu Val Asp Asn Leu Gly Gly Thr Glu Ala Pro Ile Ile Ser385 390 395 400Tyr Phe Cys Ser Leu Gly Cys Tyr Val Asn Ser Ser Asp Met Leu Lys405 410 41权利要求
1.一种分离的多肽，该多肽选自(a)一种分离的由多核苷酸编码的多肽，所述多核苷酸包含表I中一种序列；(b)包含表I中一种多肽序列的分离的多肽；和(c)表I中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中一种多核苷酸序列；(b)表I中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中一种多肽的多核苷酸序列；(d)编码表I中多肽的分离的多核苷酸；(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，该多核苷酸在所述表达载体出现在相容性宿主细胞中时能够生成权利要求1中所述的多肽。
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生成权利要求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生成所述的多肽。
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.表达所述多肽的权利要求5中所述宿主细胞的膜。
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，然后从培养基中回收所述多肽。
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。本发明还公开了所列基因的多肽和多核苷酸用于诊断试验的方法。
文档编号C07K14/47GK1444599SQ01813575
公开日2003年9月24日 申请日期2001年6月22日 优先权日2000年6月22日
发明者潘卡杰·阿加沃尔, 约翰·P·科格斯韦尔, 卡伦·S·卡布尼克, 赖英塔, 谢尔比·A·马滕森, 保罗·R·默多克, 兰德尔F·史密斯, 杰伊·C·斯特鲁姆, 向朝英, 谢青, 萨菲亚·K·里兹维 申请人:史密丝克莱恩比彻姆公司, 史密斯克莱·比奇曼公司, 葛兰素集团有限公司