CN117460532A - 用于癌的治疗和/或预防的药品 - Google Patents

用于癌的治疗和/或预防的药品 Download PDF

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CN117460532A
CN117460532A CN202280041252.1A CN202280041252A CN117460532A CN 117460532 A CN117460532 A CN 117460532A CN 202280041252 A CN202280041252 A CN 202280041252A CN 117460532 A CN117460532 A CN 117460532A
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冈野文义
赤泽大辅
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Toray Industries Inc
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Abstract

特征在于一起包含或各自分开地组合包含与CAPRIN‑1蛋白质具有免疫反应性的抗体或其片段、和拓扑异构酶I抑制剂的药品,作为用于癌的治疗和/或预防的药品是有用的。

Description

用于癌的治疗和/或预防的药品
技术领域
本发明涉及使用了针对CAPRIN-1蛋白质的抗体或其片段和拓扑异构酶I抑制剂的用于癌的治疗和/或预防的药品。
背景技术
以癌细胞上的特异抗原蛋白质为靶标的各种抗体药物由于其癌特异性,而作为副作用少的癌治疗药被应用于癌治疗。例如,多种实体癌的细胞膜表面表达细胞质增殖相关蛋白1(Cytoplasmic-activation and proliferation-associateed protein 1,CAPRIN-1),已知针对该CAPRIN-1蛋白质的抗体有望作为癌的治疗和/或预防用药物用途(专利文献1)。
近年来,临床上为了提高癌治疗药的有效性,已经使用将多种癌治疗药联合使用的治疗法作为标准的治疗法。例如,针对大肠癌联合使用伊立替康、亚叶酸(folinic acid)和5-氟尿嘧啶的治疗法,针对乳癌组合阿霉素和环磷酰胺的治疗法、或组合紫杉醇、曲妥珠单抗和帕妥珠单抗的治疗法,针对胃癌使用顺铂和5-氟尿嘧啶等多种抗癌剂进行治疗已经成为一般方法。对于以抗CAPRIN-1抗体作为有效成分的癌治疗药,已经通过与化疗剂联合使用而确认了优异的癌治疗效果(专利文献2)。但是,利用化疗剂彼此的组合的癌的治疗并不对所应用的全部癌有效,另外,虽然有时累加地提高治疗效果,但协同地大幅提高治疗效果的为数较少。
作为联合使用多种癌治疗药的癌治疗法的一个具体例,可列举嘧啶系的药剂(例如,吉西他滨)与卡铂的联合使用。吉西他滨与卡铂的联合使用也被称为CBDCA+GEM,尝试了针对非小细胞肺癌、复发了的晚期渐进性的卵巢癌、膀胱癌、乳癌、或尿路上皮癌等的治疗。卵巢癌容易转移到腹腔内、淋巴结、肝脏或肺,特别进展到III期、IV期的卵巢癌是首次治疗后2年以内复发的情况超过50%的恶性度极高的癌。针对以这样的卵巢癌为原发的转移癌使用吉西他滨与卡铂的联合使用疗法(GC),但对于从首次化疗结束到复发的间期PFI(Platinum-Free interval)为6个月以上的患者(所谓铂类制剂敏感性的患者)复发后的治疗的奏效率为40%以上,与此相对,对于从化疗结束到复发的间期PFI小于6个月的患者(所谓铂类制剂非敏感性的患者)复发后的治疗的奏效率为10%以下,预后极差(非专利文献2)。作为针对铂类制剂敏感性的卵巢癌患者的强化疗法,承认了对吉西他滨、卡铂添加贝伐珠单抗的3剂联合使用疗法(GC-BEV),但在该3剂联合使用的临床试验OCEANS中,得到了与GC相比,GC-BEV显著地延长了无恶化生存期PFS(Progression-free Survival),但全生存期OS的中值无显著性差异这样的结果(非专利文献3)。
另一方面,对于铂类制剂非敏感性的患者,卡铂等铂类制剂在指南上不能使用,要选择其他治疗法。例如,作为紫杉烷类药剂的紫杉醇、多西他赛、作为蒽环素类药剂的阿霉素及其脂质体制剂、以及作为拓扑异构酶抑制剂的依托泊苷、拓扑替康等化疗剂被承认,但虽然验证了各种施与方案,但其奏效率为10~30%,得不到满意的效果(非专利文献4~7)。
近年来,针对铂类制剂非敏感性的患者,对各种化疗剂添加作为血管新生抑制剂的贝伐珠单抗的联合使用疗法被承认。在验证了贝伐珠单抗对化疗剂的追加效果的临床试验AURELIA中,PFS相对于单剂化疗的三四个月,贝伐珠单抗的联合使用显著地延长到六七个月,但关于OS未见显著性差异,没有获得延命效果(非专利文献8)。
现有技术文献
专利文献
专利文献1:WO2010/016526号
专利文献2:WO2011/096535号
非专利文献
非专利文献1:J Clin Oncol,2012,30,1879-1887
非专利文献2:Crit Rev Oncol Hematοl,2007,64,129-138
非专利文献3:J Clin Oncol,2012,30,2039-2045
非专利文献4:J Clin Oncol,1998,16,405-410
非专利文献5:J Clin Oncol,2001,19,3312-3322
非专利文献6:J Clin Oncol,2003,21,2843-2848
非专利文献7:J Clin Oncol,2008,26,890-896
非专利文献8:J Clin Oncol,2014,32,1302-1308
发明内容
发明要解决的课题
本发明的目的是提供用于治疗和/或预防在细胞表面特异性地表达CAPRIN-1蛋白质的癌的药品。
用于解决课题的手段
本发明人进行深入研究的结果发现,与癌细胞具有免疫反应性的针对CAPRIN-1蛋白质的抗体或其片段与拓扑异构酶I抑制剂的联合使用(combination)与各自的单剂治疗相比发挥极强的抗肿瘤效果,该抗肿瘤效果是使肿瘤退缩的协同效果,以及该效果比与其他拓扑异构酶抑制剂的联合使用效果显著高,从而完成了本发明。
具体地,本发明具有以下(1)~(14)的特征。
(1)用于癌的治疗和/或预防的药品,其特征在于,一起包含或各自分开地组合包含:与CAPRIN-1蛋白质具有免疫反应性的抗体或其片段、和拓扑异构酶I抑制剂。
(2)根据(1)所述的药品,所述拓扑异构酶I抑制剂是拓扑替康或伊立替康。
(3)根据(1)或(2)所述的药品,所述抗体或其片段与CAPRIN-1蛋白质具有免疫反应性,所述CAPRIN-1蛋白质具有序列号2~30中任一偶数序列号所示的氨基酸序列、或与该氨基酸序列有80%以上的序列同一性的氨基酸序列。
(4)根据(1)~(3)的任一项所述的药品,所述抗体或其片段与在癌细胞表面上存在的CAPRIN-1蛋白质的细胞外区域具有免疫反应性。
(5)根据(1)~(4)的任一项所述的药品,所述抗体或其片段与CAPRIN-1蛋白质的部分多肽具有免疫反应性,所述CAPRIN-1蛋白质的部分多肽具有序列号31~35、296~299、308、309的任一项所示的氨基酸序列、或与该氨基酸序列有80%以上的序列同一性的氨基酸序列。
(6)根据(1)~(5)的任一项所述的药品,所述抗体是单克隆抗体或多克隆抗体。
(7)根据(1)~(6)的任一项所述的药品,所述抗体或其片段是以下(A)~(M)的任一者,
(A)包含重链可变区和轻链可变区、且与CAPRIN-1蛋白质具有免疫反应性的抗体或其片段,所述重链可变区包含序列号36所示的互补决定区CDR1、序列号37所示的互补决定区CDR2、和序列号38所示的互补决定区CDR3,所述轻链可变区包含序列号40所示的互补决定区CDR1、序列号41所示的互补决定区CDR2、和序列号42所示的互补决定区CDR3;
(B)包含重链可变区和轻链可变区、且与CAPRIN-1蛋白质具有免疫反应性的抗体或其片段,所述重链可变区包含序列号44所示的互补决定区CDR1、序列号45所示的互补决定区CDR2、和序列号46所示的互补决定区CDR3,所述轻链可变区包含序列号48所示的互补决定区CDR1、序列号49所示的互补决定区CDR2、和序列号50所示的互补决定区CDR3;
(C)包含重链可变区和轻链可变区、且与CAPRIN-1蛋白质具有免疫反应性的抗体或其片段,所述重链可变区包含序列号52所示的互补决定区CDR1、序列号53所示的互补决定区CDR2、和序列号54所示的互补决定区CDR3,所述轻链可变区包含序列号56所示的互补决定区CDR1、序列号57所示的互补决定区CDR2、和序列号58所示的互补决定区CDR3;
(D)包含重链可变区和轻链可变区、且与CAPRIN-1蛋白质具有免疫反应性的抗体或其片段,所述重链可变区包含序列号60所示的互补决定区CDR1、序列号61所示的互补决定区CDR2、和序列号62所示的互补决定区CDR3,所述轻链可变区包含序列号64所示的互补决定区CDR1、序列号65所示的互补决定区CDR2、和序列号66所示的互补决定区CDR3;
(E)包含重链可变区和轻链可变区、且与CAPRIN-1蛋白质具有免疫反应性的抗体或其片段,所述重链可变区包含序列号170所示的互补决定区CDR1、序列号171所示的互补决定区CDR2、和序列号172所示的互补决定区CDR3,所述轻链可变区包含序列号173所示的互补决定区CDR1、序列号174所示的互补决定区CDR2、和序列号175所示的互补决定区CDR3;
(F)包含重链可变区和轻链可变区、且与CAPRIN-1蛋白质具有免疫反应性的抗体或其片段,所述重链可变区包含序列号176所示的互补决定区CDR1、序列号177所示的互补决定区CDR2、和序列号178所示的互补决定区CDR3,所述轻链可变区包含序列号179所示的互补决定区CDR1、序列号180所示的互补决定区CDR2、和序列号181所示的互补决定区CDR3;
(G)包含重链可变区和轻链可变区、且与CAPRIN-1蛋白质具有免疫反应性的抗体或其片段,所述重链可变区包含序列号182所示的互补决定区CDR1、序列号183所示的互补决定区CDR2、和序列号184所示的互补决定区CDR3,所述轻链可变区包含序列号185所示的互补决定区CDR1、序列号186所示的互补决定区CDR2、和序列号187所示的互补决定区CDR3;
(H)包含重链可变区和轻链可变区、且与CAPRIN-1蛋白质具有免疫反应性的抗体或其片段,所述重链可变区包含序列号188所示的互补决定区CDR1、序列号189所示的互补决定区CDR2、和序列号190所示的互补决定区CDR3,所述轻链可变区包含序列号191所示的互补决定区CDR1、序列号192所示的互补决定区CDR2、和序列号193所示的互补决定区CDR3;
(I)包含重链可变区和轻链可变区、且与CAPRIN-1蛋白质具有免疫反应性的抗体或其片段,所述重链可变区包含序列号146所示的互补决定区CDR1、序列号147所示的互补决定区CDR2、和序列号148所示的互补决定区CDR3,所述轻链可变区包含序列号149所示的互补决定区CDR1、序列号150所示的互补决定区CDR2、和序列号151所示的互补决定区CDR3;
(J)包含重链可变区和轻链可变区、且与CAPRIN-1蛋白质具有免疫反应性的抗体或其片段,所述重链可变区包含序列号272所示的互补决定区CDR1、序列号273所示的互补决定区CDR2、和序列号274所示的互补决定区CDR3,所述轻链可变区包含序列号275所示的互补决定区CDR1、序列号276所示的互补决定区CDR2、和序列号277所示的互补决定区CDR3;
(K)包含重链可变区和轻链可变区、且与CAPRIN-1蛋白质具有免疫反应性的抗体或其片段,所述重链可变区包含序列号290所示的互补决定区CDR1、序列号291所示的互补决定区CDR2、和序列号292所示的互补决定区CDR3,所述轻链可变区包含序列号293所示的互补决定区CDR1、序列号294所示的互补决定区CDR2、和序列号295所示的互补决定区CDR3;
(L)包含重链可变区和轻链可变区、且与CAPRIN-1蛋白质具有免疫反应性的抗体或其片段,所述重链可变区包含序列号301所示的互补决定区CDR1、序列号302所示的互补决定区CDR2、和序列号303所示的互补决定区CDR3,所述轻链可变区包含序列号305所示的互补决定区CDR1、序列号306所示的互补决定区CDR2、和序列号307所示的互补决定区CDR3;
(M)包含重链可变区和轻链可变区、且与CAPRIN-1蛋白质具有免疫反应性的抗体或其片段,所述重链可变区包含序列号134所示的互补决定区CDR1、序列号135所示的互补决定区CDR2、和序列号136所示的互补决定区CDR3,所述轻链可变区包含序列号137所示的互补决定区CDR1、序列号138所示的互补决定区CDR2、和序列号139所示的互补决定区CDR3。
(8)根据(1)~(7)的任一项所述的药品,所述抗体或其片段是以下(a)~(al)的任一者,
(a)重链可变区包含序列号39的氨基酸序列、且轻链可变区包含序列号43的氨基酸序列的抗体或其片段;
(b)重链可变区包含序列号47的氨基酸序列、且轻链可变区包含序列号51的氨基酸序列的抗体或其片段;
(c)重链可变区包含序列号55的氨基酸序列、且轻链可变区包含序列号59的氨基酸序列的抗体或其片段;
(d)重链可变区包含序列号63的氨基酸序列、且轻链可变区包含序列号67的氨基酸序列的抗体或其片段;
(e)重链可变区包含序列号68的氨基酸序列、且轻链可变区包含序列号69的氨基酸序列的抗体或其片段;
(f)重链可变区包含序列号70的氨基酸序列、且轻链可变区包含序列号71的氨基酸序列的抗体或其片段;
(g)重链可变区包含序列号72的氨基酸序列、且轻链可变区包含序列号73的氨基酸序列的抗体或其片段;
(h)重链可变区包含序列号74的氨基酸序列、且轻链可变区包含序列号75的氨基酸序列的抗体或其片段;
(i)重链可变区包含序列号76的氨基酸序列、且轻链可变区包含序列号77的氨基酸序列的抗体或其片段;
(j)重链可变区包含序列号78的氨基酸序列、且轻链可变区包含序列号79的氨基酸序列的抗体或其片段;
(k)重链可变区包含序列号80的氨基酸序列、且轻链可变区包含序列号81的氨基酸序列的抗体或其片段;
(l)重链可变区包含序列号82的氨基酸序列、且轻链可变区包含序列号83的氨基酸序列的抗体或其片段;
(m)重链可变区包含序列号84的氨基酸序列、且轻链可变区包含序列号85的氨基酸序列的抗体或其片段;
(n)重链可变区包含序列号86的氨基酸序列、且轻链可变区包含序列号87的氨基酸序列的抗体或其片段;
(o)重链可变区包含序列号88的氨基酸序列、且轻链可变区包含序列号89的氨基酸序列的抗体或其片段;
(p)重链可变区包含序列号90的氨基酸序列、且轻链可变区包含序列号91的氨基酸序列的抗体或其片段;
(q)重链可变区包含序列号92的氨基酸序列、且轻链可变区包含序列号93的氨基酸序列的抗体或其片段;
(r)重链可变区包含序列号94的氨基酸序列、且轻链可变区包含序列号95的氨基酸序列的抗体或其片段;
(s)重链可变区包含序列号96的氨基酸序列、且轻链可变区包含序列号97的氨基酸序列的抗体或其片段;
(t)重链可变区包含序列号98的氨基酸序列、且轻链可变区包含序列号99的氨基酸序列的抗体或其片段;
(u)重链可变区包含序列号100的氨基酸序列、且轻链可变区包含序列号101的氨基酸序列的抗体或其片段;
(v)重链可变区包含序列号102的氨基酸序列、且轻链可变区包含序列号103的氨基酸序列的抗体或其片段;
(w)重链可变区包含序列号104的氨基酸序列、且轻链可变区包含序列号105的氨基酸序列的抗体或其片段;
(x)重链可变区包含序列号106的氨基酸序列、且轻链可变区包含序列号107的氨基酸序列的抗体或其片段;
(y)重链可变区包含序列号108的氨基酸序列、且轻链可变区包含序列号109的氨基酸序列的抗体或其片段;
(z)重链可变区包含序列号110的氨基酸序列、且轻链可变区包含序列号111的氨基酸序列的抗体或其片段;
(aa)重链可变区包含序列号112的氨基酸序列、且轻链可变区包含序列号113的氨基酸序列的抗体或其片段;
(ab)重链可变区包含序列号114的氨基酸序列、且轻链可变区包含序列号115的氨基酸序列的抗体或其片段;
(ac)重链可变区包含序列号116的氨基酸序列、且轻链可变区包含序列号117的氨基酸序列的抗体或其片段;
(ad)重链可变区包含序列号118的氨基酸序列、且轻链可变区包含序列号119的氨基酸序列的抗体或其片段;
(ae)重链可变区包含序列号120的氨基酸序列、且轻链可变区包含序列号121的氨基酸序列的抗体或其片段;
(af)重链可变区包含序列号122的氨基酸序列、且轻链可变区包含序列号123的氨基酸序列的抗体或其片段;
(ag)重链可变区包含序列号124的氨基酸序列、且轻链可变区包含序列号125的氨基酸序列的抗体或其片段;
(ah)重链可变区包含序列号126的氨基酸序列、且轻链可变区包含序列号127的氨基酸序列的抗体或其片段;
(ai)重链可变区包含序列号128的氨基酸序列、且轻链可变区包含序列号129的氨基酸序列的抗体或其片段;
(aj)重链可变区包含序列号130的氨基酸序列、且轻链可变区包含序列号131的氨基酸序列的抗体或其片段;
(ak)重链可变区包含序列号132的氨基酸序列、且轻链可变区包含序列号133的氨基酸序列的抗体或其片段;
(al)重链可变区包含序列号300的氨基酸序列、且轻链可变区包含序列号304的氨基酸序列的抗体或其片段。
(9)根据(1)~(8)的任一项所述的药品,所述抗体是人抗体、人源化抗体、嵌合抗体或单链抗体。
(10)根据(1)~(9)的任一项所述的药品,所述癌是在细胞膜表面表达CAPRIN-1蛋白质的癌。
(11)根据(1)~(10)的任一项所述的药品,所述癌是卵巢癌、胆管癌、乳癌、肾癌、胰癌、大肠癌、黑素瘤、肺癌、肾细胞癌、霍奇金淋巴瘤、头颈癌、胃癌、间皮癌、结肠/直肠癌、食道癌、食管胃结合部癌、肝细胞癌、胶质母细胞瘤、尿路上皮癌、膀胱癌、子宫癌、原发性中枢神经系统淋巴瘤、原发性睾丸淋巴瘤、胆道癌、脑肿瘤、前列腺癌、白血病、淋巴瘤、肝癌、肉瘤、纤维肉瘤、肥大细胞瘤、肾上腺皮质癌、尤因肉瘤、多发性骨髓瘤、睾丸癌、甲状腺癌、基底细胞癌、佩吉特病或皮肤癌。
(12)癌的治疗和/或预防用药物组合物的药效增强剂,所述癌的治疗和/或预防用药物组合物以与CAPRIN-1蛋白质具有免疫反应性的抗体或其片段作为有效成分,所述药效增强剂以拓扑异构酶I抑制剂作为有效成分。
(13)癌的治疗和/或预防用药物组合物的药效增强剂,所述癌的治疗和/或预防用药物组合物以拓扑异构酶I抑制剂作为有效成分,所述药效增强剂以与CAPRIN-1蛋白质具有免疫反应性的抗体或其片段作为有效成分。
(14)用于癌的治疗和/或预防的方法,其特征在于,将与CAPRIN-1蛋白质具有免疫反应性的抗体或其片段、和拓扑异构酶I抑制剂一起或各自分开地施与受检者。
发明的效果
本发明所涉及的针对CAPRIN-1蛋白质的抗体或其片段与拓扑异构酶I抑制剂的联合使用,与针对CAPRIN-1蛋白质的抗体或其片段单独以及拓扑异构酶I抑制剂单独相比发挥强的抗肿瘤效果。进而本发明所涉及的针对CAPRIN-1蛋白质的抗体或其片段与拓扑异构酶I抑制剂的联合使用,与其他拓扑异构酶抑制剂与针对CAPRIN-1蛋白质的抗体的联合使用相比显示强的抗肿瘤效果。因此针对CAPRIN-1蛋白质的抗体或其片段与拓扑异构酶I抑制剂的联合使用对癌的治疗、预防有效。
附图说明
图1是显示抗CAPRIN-1抗体与拓扑替康的联合使用对移植了表达CAPRIN-1的人癌细胞株BT474的NOD-SCID小鼠的抗肿瘤效果的图。参考编号1显示代替药物而施与PBS时的小鼠的肿瘤的大小,参考编号2显示施与拓扑替康低用量(3mg/kg)时的小鼠的肿瘤的大小,参考编号3显示施与拓扑替康高用量(10mg/kg)时的小鼠的肿瘤的大小,参考编号4显示施与抗CAPRIN-1抗体时的小鼠的肿瘤的大小,参考编号5显示联合施与抗CAPRIN-1抗体与拓扑替康低用量(3mg/kg)时的小鼠的肿瘤的大小,参考编号6显示联合施与抗CAPRIN-1抗体与拓扑替康高用量(10mg/kg)时的小鼠的肿瘤的大小。
图2是显示抗CAPRIN-1抗体与依托泊苷的联合使用对移植了表达CAPRIN-1的人癌细胞株BT474的NOD-SCID小鼠的抗肿瘤效果的图。参考编号7显示代替药物而施与PBS时的小鼠的肿瘤的大小,参考编号8显示施与依托泊苷低用量(5mg/kg)时的小鼠的肿瘤的大小,参考编号9显示施与依托泊苷高用量(15mg/kg)时的小鼠的肿瘤的大小,参考编号10显示施与抗CAPRIN-1抗体时的小鼠的肿瘤的大小,参考编号11显示联合施与抗CAPRIN-1抗体与依托泊苷低用量(5mg/kg)时的小鼠的肿瘤的大小,参考编号12显示联合施与抗CAPRIN-1抗体与依托泊苷高用量(15mg/kg)时的小鼠的肿瘤的大小。
具体实施方式
本发明中使用的针对CAPRIN-1蛋白质的抗体或其片段(以下,将它们总称为“抗CAPRIN-1抗体”)与拓扑异构酶I抑制剂的联合使用所产生的抗肿瘤活性如后所述,通过在生物体内调查对荷癌动物的肿瘤增殖的抑制来评价。
本说明书中,“联合使用”或“组合”是指将抗CAPRIN-1抗体与拓扑异构酶I抑制剂向同一生物体同时或设置规定的间隔作为各自独立的有效成分进行施与。其间隔可以是同时施与,也可以是30分钟后、或1小时后、3小时后、6小时后、12小时后、1天后、3天后、5天后、7天后、2周后、3周后、4周后。当抗CAPRIN-1抗体或拓扑异构酶I抑制剂在生物体内显示其活性时,可施与任一方。另外,可以先施与抗CAPRIN-1抗体,也可以先施与拓扑异构酶I抑制剂。
本发明所涉及的抗CAPRIN-1抗体可以是单克隆抗体或多克隆抗体,优选为单克隆抗体,只要本发明的抗体能够发挥抗肿瘤活性,就可以是任何种类的抗体,抗体是重组抗体、人抗体、人源化抗体、嵌合抗体、非人动物抗体。
另外,本发明中作为癌的治疗和/或预防的对象的受试者是人、宠物、家畜类、竞技用动物等哺乳动物,优选的受试者是人。
以下对于本发明所涉及的抗CAPRIN-1抗体、拓扑异构酶I抑制剂、包含它们作为有效成分的药品以及癌的治疗和/或预防方法进行说明。
<抗CAPRIN-1抗体>
作为与本发明中使用的抗CAPRIN-1抗体具有免疫反应性的抗原的具体例的、具有序列号2~30中的偶数序列号的任一项所示的氨基酸序列的CAPRIN-1蛋白质中,序列号6、8、10、12和14所示的氨基酸序列是犬的CAPRIN-1蛋白质的氨基酸序列,序列号2和4所示的氨基酸序列是人的CAPRIN-1蛋白质的氨基酸序列,序列号16所示的氨基酸序列是牛的CAPRIN-1蛋白质的氨基酸序列,序列号18所示的氨基酸序列是马的CAPRIN-1蛋白质的氨基酸序列,序列号20~28所示的氨基酸序列是小鼠的CAPRIN-1蛋白质的氨基酸序列,序列号30所示的氨基酸序列是鸡的CAPRIN-1蛋白质的氨基酸序列。
另外,本发明中使用的抗CAPRIN-1抗体也可以是与相对于所述序列号2~30中的偶数序列号的任一项所示的氨基酸序列有80%以上、优选为90%以上、更优选为95%以上、进一步优选为99%以上的序列同一性的CAPRIN-1蛋白质的变异体有免疫反应性的抗体。这里,“%序列同一性”是将2个序列在导入间隙或不导入间隙的情况下以形成最大的类似度(或一致度)的方式比对(排列)时,相同氨基酸(或碱基)相对于氨基酸(或碱基)的总数的百分比(%)。
本发明中抗CAPRIN-1抗体是指与CAPRIN-1蛋白质的全长或其片段具有免疫反应性的抗体或其片段。这里,“免疫反应性”是指在生物体内抗体与CAPRIN-1蛋白质或其部分多肽结合的特性。
本发明中使用的抗CAPRIN-1抗体可以是单克隆抗体或多克隆抗体。
与CAPRIN-1蛋白质的全长或其片段具有免疫反应性的多克隆抗体(抗CAPRIN-1多克隆抗体)可以通过例如将天然的CAPRIN-1蛋白质、或与GST等的融合蛋白质、或其部分肽免疫小鼠、产生人抗体的小鼠、大鼠、兔、鸡等,获得血清。将所得的血清通过例如硫酸铵沉淀、蛋白A、蛋白G、DEAE离子交换柱、偶联了CAPRIN-1蛋白质或部分肽的亲和柱等而获得。
关于上述免疫中使用的CAPRIN-1蛋白质的全长或其片段,CAPRIN-1及其同源物的碱基序列和氨基酸序列例如可以通过登录GenBank(美国NCBI),利用BLAST、FASTA等算法(Karlin and Altschul,Proc.Natl.Acad.Sci.USA,90:5873-5877,1993;Altschul etal.,Nucleic Acids Res.25:3389-3402,1997)来得到。另外,其CAPRIN-1蛋白质的制作方法可以通过参照WO2014/012479获得,也可以使用表达CAPRIN-1蛋白质的细胞等。
与CAPRIN-1蛋白质的全长或其片段具有免疫反应性的单克隆抗体(抗CAPRIN-1单克隆抗体)例如可以通过将表达CAPRIN-1的乳癌细胞SK-BR-3、CAPRIN-1蛋白质的全长或其片段等施与小鼠进行免疫,将从该小鼠分离的脾脏细胞与骨髓瘤细胞,从所得的融合细胞(杂交瘤)选择产生抗CAPRIN-1单克隆抗体的克隆,从而获得。由所选择的杂交瘤产生的抗体可以通过与前述的多克隆抗体的纯化方法同样的方法获得。
本发明中使用的抗体包含人抗体、人源化抗体、嵌合抗体、非人动物抗体。
人抗体可以将感染了EB病毒的人淋巴细胞用蛋白质、蛋白质表达细胞或其溶解物致敏,使致敏淋巴细胞与来源于人的U266细胞等骨髓瘤细胞进行细胞融合,从融合细胞获得与CAPRIN-1蛋白质的全长或其片段具有免疫反应性的抗体。
人源化抗体是也称为重构(reshaped)人抗体的改变抗体。人源化抗体通过将来源于免疫动物的抗体的互补决定区移植到人抗体的互补性决定区中来构建。作为其一般方法的基因重组方法也是广为人知的技术。具体来说,通过PCR法,由以末端部具有重叠部分的方式制作的数个寡核苷酸,由其合成以将例如小鼠抗体、兔抗体的互补决定区与人抗体的框架区连接的方式设计的DNA序列。将所得的DNA与编码人抗体恒定区的DNA连接,接着整合到表达载体中,将其导入宿主而使其产生,从而得到人源化抗体(参照欧洲专利申请公开第EP239400号、国际公开号WO96/02576)。介由互补决定区连接的人抗体的框架区可以选择使互补性决定区形成良好的抗原结合部位的框架区。根据需要,也可以替换抗体的可变区中的框架区的氨基酸,以使重构人抗体的互补性决定区形成适当的抗原结合部位(Sato K.etal.,Cancer Research 1993,53:851-856)。另外,也可以替换为来源于各种人抗体的框架区(参照WO99/51743)。
抗体通常是至少包含2条重链和2条轻链的杂多聚体糖蛋白质。抗体由2条相同的轻链和2条相同的重链构成。重链在一端具有重链可变区,几个恒定区与其相连。轻链在一端具有轻链可变区,几个恒定区与其相连。可变区显示被称为互补决定区(CDR)的特定可变区,对抗体赋予结合特异性。可变区中相对保守的部分被称为框架区(FR)。完整的重链和轻链的可变区包含分别由3个CDR(CDR1~CDR3)连接而成的4个FR。
此外,来源于人的重链和轻链的恒定区和可变区的序列可以从例如NCBI(美国:GenBank、UniGene等)获得,例如,人IgG1的重链恒定区可以参照登记号J00228的序列,人IgG2的重链恒定区可以参照登记号J00230的序列,人轻链κ恒定区可以参照登记号V00557、X64135、X64133等的序列,人轻链λ恒定区可以参照登记号X64132、X64134等的序列。
嵌合抗体是将来源于不同动物的序列组合而制作的抗体,例如,包含小鼠抗体的重链可变区和轻链可变区以及人抗体的重链可变区和轻链可变区的恒定区的抗体等。嵌合抗体的制作可以使用公知的方法进行,例如可以通过将编码抗体V区的DNA与编码人抗体C区的DNA连接,将其整合到表达载体中并导入宿主,而使其产生,从而得到。
非人动物抗体可以按照公知的方法使致敏抗原免疫动物,作为一般的方法,通过将致敏抗原注射到小鼠等的动物的腹腔内或皮内或皮下来获得。注射致敏抗原时,可以与以CFA(弗氏完全佐剂)为代表的各种佐剂适量混合而对动物多次施与。免疫动物,确认了血清中含有抗CAPRIN-1抗体之后获得血清,如前所述,通过硫酸铵沉淀、蛋白A、蛋白G、DEAE离子交换柱、偶联了CAPRIN-1蛋白质或部分肽的亲和柱等而获得。另外,在从非人动物获得单克隆抗体时,可以通过从免疫后的动物采集免疫细胞,与骨髓瘤细胞进行细胞融合来获得。所述免疫细胞与骨髓瘤细胞的细胞融合可以依照公知的方法进行(参照Kohler,G.andMilstein,C.Methods Enzymol.(1981)73,3-46)。
本发明中使用的抗体也可以作为从杂交瘤克隆抗体基因,整合到适当的载体中,将其导入宿主,使用基因重组技术使其产生的基因重组型抗体获得(参照Carl,A.K.Borrebaeck,James,W.Larrick,THERAPEUTIC MONOCLONAL ANTIBODIES,Published inthe United Kingdom by MACMILLAN PUBLISHERS LTD,1990)。
本发明中使用的抗CAPRIN-1抗体可以是将可变区(例如FR)、恒定区中的氨基酸替换成其他氨基酸而得的抗体。氨基酸替换为1或多个、例如小于15个、小于10个、8个以下、6个以下、5个以下、4个以下、3个以下、或2个以下的氨基酸、优选为1~9个氨基酸的替换,替换后的抗体应当是与未替换抗体相比,对抗原特异地结合的性质、与抗原的结合亲和性为同等或其以上,对人应用时不发生排斥反应的抗体。氨基酸替换期望是保守的氨基酸替换,这是电荷、侧链、极性、芳香族性等性质类似的氨基酸间的替换。性质类似的氨基酸例如可以分类为碱性氨基酸(精氨酸、赖氨酸、组氨酸)、酸性氨基酸(天冬氨酸、谷氨酸)、无电荷极性氨基酸(甘氨酸、天冬酰胺、谷氨酰胺、丝氨酸、苏氨酸、半胱氨酸、酪氨酸)、无极性氨基酸(亮氨酸、异亮氨酸、丙氨酸、缬氨酸、脯氨酸、苯丙氨酸、色氨酸、蛋氨酸)、支链氨基酸(苏氨酸、缬氨酸、异亮氨酸)、芳香族氨基酸(苯丙氨酸、酪氨酸、色氨酸、组氨酸)等。
本发明中使用的抗CAPRIN-1抗体与癌细胞表面上的CAPRIN-1蛋白质的结合亲和性越高,则越能期待更强的抗肿瘤效果。期望结合常数(亲和常数)Ka(kon/koff)优选为至少107M-1、至少108M-1、至少5×108M-1、至少109M-1、至少5×109M-1、至少1010M-1、至少5×1010M-1、至少1011M-1、至少5×1011M-1、至少1012M-1、或至少1013M-1
本发明中使用的抗CAPRIN-1抗体可以被化学修饰,作为这样的抗体修饰物,可列举例如,与聚乙二醇(PEG)、抗肿瘤性化合物(例如,下述例示的抗肿瘤剂)等各种分子结合的抗体。在本发明的抗体修饰物中,不限定结合的物质。为了得到这样的抗体修饰物,可以通过对所得的抗体实施化学修饰来得到。这些方法在本领域已经被确立。本发明中使用的抗CAPRIN-1抗体通过将抗体的重链恒定区的氨基酸替换1个、2个或数个,或除去与结合于重链恒定区的N-糖苷键糖链中的N-乙酰葡糖胺结合的岩藻糖,能够提高抗CAPRIN-1抗体对效应细胞的结合力。上述可以是单独的氨基酸替换,另外,也可以是与结合了岩藻糖的抗体的组合物。
将重链恒定区的氨基酸替换了1个、2个或数个的抗体可以参照例如WO2004/063351、WO2011/120135、美国专利8388955、WO2011/005481、美国专利6737056、WO2005/063351来制作。
除去了重链恒定区中的N-糖苷键糖链中的N-乙酰葡糖胺所附带的岩藻糖的抗体或产生该抗体的细胞,可以参照美国专利6602684号、欧洲专利1914244、美国专利7579170来制作。除去了与结合于重链恒定区的N-糖苷键糖链中的N-乙酰葡糖胺结合的岩藻糖的抗体和结合了岩藻糖的抗体的组合物或产生该组合物的细胞,可以参照例如美国专利8642292号来制作。
本发明中使用的抗CAPRIN-1多克隆抗体、抗CAPRIN-1单克隆抗体、抗体的制作方法、纯化方法以及用于免疫的CAPRIN-1蛋白质或其部分多肽的制作方法可以参照WO2010/016526、WO2011/096517、WO2011/096528、WO2011/096519、WO2011/096533、WO2011/096534、WO2011/096535、WO2013/018886、WO2013/018894、WO2013/018892、WO2013/018891、WO2013/018889、WO2013/018883、WO2013/125636、WO2013/125654、WO2013/125630、WO2013/125640、WO2013/147169、WO2013/147176以及WO2015/020212获得。
作为本发明中的抗CAPRIN-1抗体的具体例,可列举前述的WO2010/016526、WO2011/096517、WO2011/096528、WO2011/096519、WO2011/096533、WO2011/096534、WO2011/096535、WO2013/018886、WO2013/018894、WO2013/018892、WO2013/018891、WO2013/018889、WO2013/018883、WO2013/125636、WO2013/125654、WO2013/125630、WO2013/125640、WO2013/147169、WO2013/147176以及WO2015/020212中记载的抗CAPRIN-1抗体,但作为优选的抗CAPRIN-1抗体可列举以下抗体。
与具有序列号2或序列号4所示的氨基酸序列或相对于该氨基酸序列的序列同一性为80%以上(优选为85%以上、更优选为90%以上、进一步优选为95%以上、更进一步优选为99%以上)的氨基酸序列的CAPRIN-1蛋白质的部分多肽具有免疫反应性的抗体或其片段。
与具有序列号31所示的氨基酸序列或相对于该氨基酸序列的序列同一性为80%以上(优选为85%以上、更优选为90%以上、进一步优选为95%以上)的氨基酸序列的CAPRIN-1蛋白质的部分多肽具有免疫反应性的抗体或其片段。优选为含有包含序列号36、37和38的互补决定区(分别为CDR1、CDR2和CDR3)的重链可变区、和包含序列号40、41和42的互补决定区(分别为CDR1、CDR2和CDR3)的轻链可变区,且与CAPRIN-1蛋白质具有免疫反应性的抗体或其片段;或者含有包含序列号140、141和142的互补决定区(分别为CDR1、CDR2和CDR3)的重链可变区、和包含序列号143、144和145的互补决定区(分别为CDR1、CDR2和CDR3)的轻链可变区,且与CAPRIN-1蛋白质具有免疫反应性的抗体或其片段;或者含有包含序列号164、165和166的互补决定区(分别为CDR1、CDR2和CDR3)的重链可变区、和包含序列号167、168和169的互补决定区(分别为CDR1、CDR2和CDR3)的轻链可变区,且与CAPRIN-1蛋白质具有免疫反应性的抗体或其片段。更优选为重链可变区包含序列号39的氨基酸序列、且轻链可变区包含序列号43的氨基酸序列的抗体或其片段;或者重链可变区包含序列号70的氨基酸序列、且轻链可变区包含序列号71的氨基酸序列的抗体或其片段;或者重链可变区包含序列号78的氨基酸序列、且轻链可变区包含序列号79的氨基酸序列的抗体或其片段。
与具有序列号33所示的氨基酸序列或相对于该氨基酸序列的序列同一性为80%以上(优选为85%以上、更优选为90%以上、进一步优选为95%以上)的氨基酸序列的CAPRIN-1蛋白质的部分多肽具有免疫反应性的抗体或其片段。优选为含有包含序列号60、61和62的互补决定区(分别为CDR1、CDR2和CDR3)的重链可变区、和包含序列号64、65和66的互补决定区(分别为CDR1、CDR2和CDR3)的轻链可变区,且与CAPRIN-1蛋白质具有免疫反应性的抗体或其片段。更优选为重链可变区包含序列号63的氨基酸序列、且轻链可变区包含序列号67的氨基酸序列的抗体或其片段。
与具有序列号32所示的氨基酸序列或相对于该氨基酸序列的序列同一性为80%以上(优选为85%以上、更优选为90%以上、进一步优选为95%以上)的氨基酸序列的CAPRIN-1蛋白质的部分多肽具有免疫反应性的抗体或其片段。优选为含有包含序列号52、53和54的互补决定区(分别为CDR1、CDR2和CDR3)的重链可变区、和包含序列号56、57和58的互补决定区(分别为CDR1、CDR2和CDR3)的轻链可变区,且与CAPRIN-1蛋白质具有免疫反应性的抗体或其片段。更优选为重链可变区包含序列号55的氨基酸序列、且轻链可变区包含序列号59的氨基酸序列的抗体或其片段。
与具有序列号34所示的氨基酸序列或相对于该氨基酸序列的序列同一性为80%以上(优选为85%以上、更优选为90%以上、进一步优选为95%以上)的氨基酸序列的CAPRIN-1蛋白质的部分多肽具有免疫反应性的抗体或其片段。优选为含有包含序列号170、171和172的互补决定区(分别为CDR1、CDR2和CDR3)的重链可变区、和包含序列号173、174和175的互补决定区(分别为CDR1、CDR2和CDR3)的轻链可变区,且与CAPRIN-1蛋白质具有免疫反应性的抗体或其片段;或者含有包含序列号176、177和178的互补决定区(分别为CDR1、CDR2和CDR3)的重链可变区、和包含序列号179、180和181的互补决定区(分别为CDR1、CDR2和CDR3)的轻链可变区,且与CAPRIN-1蛋白质具有免疫反应性的抗体或其片段。更优选为重链可变区包含序列号80的氨基酸序列、且轻链可变区包含序列号81的氨基酸序列的抗体或其片段;或者重链可变区包含序列号82的氨基酸序列、且轻链可变区包含序列号83的氨基酸序列的抗体或其片段。
与具有序列号35所示的氨基酸序列或相对于该氨基酸序列的序列同一性为80%以上(优选为85%以上、更优选为90%以上、进一步优选为95%以上)的氨基酸序列的CAPRIN-1蛋白质的部分多肽具有免疫反应性的抗体或其片段。优选为含有包含序列号182、183和184的互补决定区(分别为CDR1、CDR2和CDR3)的重链可变区、和包含序列号185、186和187的互补决定区(分别为CDR1、CDR2和CDR3)的轻链可变区,且与CAPRIN-1蛋白质具有免疫反应性的抗体或其片段;或者含有包含序列号188、189和190的互补决定区(分别为CDR1、CDR2和CDR3)的重链可变区、和包含序列号191、192和193的互补决定区(分别为CDR1、CDR2和CDR3)的轻链可变区,且与CAPRIN-1蛋白质具有免疫反应性的抗体或其片段。更优选为重链可变区包含序列号84的氨基酸序列、且轻链可变区包含序列号85的氨基酸序列的抗体或其片段;或者重链可变区包含序列号86的氨基酸序列、且轻链可变区包含序列号87的氨基酸序列的抗体或其片段。
含有包含序列号44、45和46的互补决定区(分别为CDR1、CDR2和CDR3)的重链可变区、和包含序列号48、49和50的互补决定区(分别为CDR1、CDR2和CDR3)的轻链可变区,且与CAPRIN-1蛋白质具有免疫反应性的抗体或其片段。优选为重链可变区包含序列号47的氨基酸序列、且轻链可变区包含序列号51的氨基酸序列的抗体或其片段。
与具有序列号296所示的氨基酸序列或相对于该氨基酸序列的序列同一性为80%以上(优选为85%以上、更优选为90%以上、进一步优选为95%以上)的氨基酸序列的CAPRIN-1蛋白质的部分多肽具有免疫反应性的抗体或其片段。优选为含有包含序列号146、147和148的互补决定区(分别为CDR1、CDR2和CDR3)的重链可变区、和包含序列号149、150和151的互补决定区(分别为CDR1、CDR2和CDR3)的轻链可变区,且与CAPRIN-1蛋白质具有免疫反应性的抗体或其片段。更优选为重链可变区包含序列号72的氨基酸序列、且轻链可变区包含序列号73的氨基酸序列的抗体或其片段。
与具有序列号297所示的氨基酸序列或相对于该氨基酸序列的序列同一性为80%以上(优选为85%以上、更优选为90%以上、进一步优选为95%以上)的氨基酸序列的CAPRIN-1蛋白质的部分多肽具有免疫反应性的抗体或其片段。优选为含有包含序列号272、273和274的互补决定区(分别为CDR1、CDR2和CDR3)的重链可变区、和包含序列号275、276和277的互补决定区(分别为CDR1、CDR2和CDR3)的轻链可变区,且与CAPRIN-1蛋白质具有免疫反应性的抗体或其片段。更优选为重链可变区包含序列号114的氨基酸序列、且轻链可变区包含序列号115的氨基酸序列的抗体或其片段。
与具有序列号298所示的氨基酸序列或相对于该氨基酸序列的序列同一性为80%以上(优选为85%以上、更优选为90%以上、进一步优选为95%以上)的氨基酸序列的CAPRIN-1蛋白质的部分多肽具有免疫反应性的抗体或其片段。优选为含有包含序列号290、291和292的互补决定区(分别为CDR1、CDR2和CDR3)的重链可变区、和包含序列号293、294和295的互补决定区(分别为CDR1、CDR2和CDR3)的轻链可变区,且与CAPRIN-1蛋白质具有免疫反应性的抗体或其片段。更优选为重链可变区包含序列号120的氨基酸序列、且轻链可变区包含序列号121的氨基酸序列的抗体或其片段。
与具有序列号299所示的氨基酸序列或相对于该氨基酸序列的序列同一性为80%以上(优选为85%以上、更优选为90%以上、进一步优选为95%以上)的氨基酸序列的CAPRIN-1蛋白质的部分多肽具有免疫反应性的抗体或其片段。优选为含有包含序列号301、302和303的互补决定区(分别为CDR1、CDR2和CDR3)的重链可变区、和包含序列号305、306和307的互补决定区(分别为CDR1、CDR2和CDR3)的轻链可变区,且与CAPRIN-1蛋白质具有免疫反应性的抗体或其片段。更优选为重链可变区包含序列号300的氨基酸序列、且轻链可变区包含序列号304的氨基酸序列的抗体或其片段。
与具有序列号308所示的氨基酸序列或相对于该氨基酸序列的序列同一性为80%以上(优选为85%以上、更优选为90%以上、进一步优选为95%以上)的氨基酸序列的CAPRIN-1蛋白质的部分多肽具有免疫反应性的抗体或其片段。优选为含有包含序列号134、135和136的互补决定区(分别为CDR1、CDR2和CDR3)的重链可变区、和包含序列号137、138和139的互补决定区(分别为CDR1、CDR2和CDR3)的轻链可变区,且与CAPRIN-1蛋白质具有免疫反应性的抗体或其片段。更优选为重链可变区包含序列号68的氨基酸序列、且轻链可变区包含序列号69的氨基酸序列的抗体或其片段。
与具有序列号309所示的氨基酸序列或相对于该氨基酸序列的序列同一性为80%以上(优选为85%以上、更优选为90%以上、进一步优选为95%以上)的氨基酸序列的CAPRIN-1蛋白质的部分多肽具有免疫反应性的抗体或其片段。优选为含有包含序列号134、135和136的互补决定区(分别为CDR1、CDR2和CDR3)的重链可变区、和包含序列号137、138和139的互补决定区(分别为CDR1、CDR2和CDR3)的轻链可变区,且与CAPRIN-1蛋白质具有免疫反应性的抗体或其片段。更优选为重链可变区包含序列号68的氨基酸序列、且轻链可变区包含序列号69的氨基酸序列的抗体或其片段。
另外,还优选使用以下的抗CAPRIN-1抗体。
重链可变区包含序列号68的氨基酸序列、且轻链可变区包含序列号69的氨基酸序列的抗体或其片段。
重链可变区包含序列号70的氨基酸序列、且轻链可变区包含序列号71的氨基酸序列的抗体或其片段。
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在后述的实施例中,通过将针对CAPRIN-1蛋白质的全长、在癌细胞的细胞膜表面表达的区域的部分多肽的上述多克隆抗体或单克隆抗体与拓扑异构酶I抑制剂组合,在荷癌生物体内确认了其强的抗肿瘤效果。
<拓扑异构酶I抑制剂>
拓扑异构酶I抑制剂选择性地结合与DNA形成复合体的I型拓扑异构酶而使其结构稳定化,引起DNA螺旋结构的解旋阻碍和DNA的片段化,细胞分裂停止而诱导细胞死亡。为了将拓扑异构酶I抑制剂施与生物体,可以包含适当的等渗剂或pH或适当的剂型。作为拓扑异构酶I抑制剂的具体例为拓扑替康(Nogitecan)或伊立替康。拓扑异构酶I抑制剂可以通过本领域技术人员公知的手法进行化学合成而获得。
<拓扑替康>
拓扑替康是作为由喜树的树皮提取出的天然物的喜树碱的半合成衍生物,是用CAS号123948-87-8(水合物为119413-54-6)表示的分子量约421.4的I型拓扑异构酶抑制剂。此外,本说明书中仅称为“拓扑替康”的情况下,只要不特别说明,就包含拓扑替康盐酸盐和拓扑替康盐酸盐水合物。拓扑替康盐酸盐的IUPAC名为(S)-10-[(二甲基氨基)甲基]-4-乙基-4,9-二羟基-1H-吡喃并[3’,4’:6,7]中氮茚并[1,2-b]-喹啉-3,14(4H,12H)-二酮单盐酸盐,作为其他的表述,用Nogitecan hydrochloride(Nogitecan盐酸盐)表示。作为以拓扑替康盐酸盐为有效成分的药品,“Hycamtin(注册商标)”、“Potactasol(注册商标)”上市,在本发明中利用拓扑替康时可以适当利用这些药品。
<伊立替康>
本发明所涉及的伊立替康是用CAS号100286-90-6(水合物为136572-09-3)表示的分子量约586.678的I型拓扑异构酶抑制剂。此外,本说明书中仅称为“伊立替康”的情况下,只要不特别说明,就包含伊立替康盐酸盐和伊立替康盐酸盐水合物。作为以伊立替康盐酸盐为有效成分的药品,“Campto(注册商标)”、“Topotecin”(注册商标)、“Onivyde(注册商标)”等上市,在本发明中利用伊立替康时可以适当利用这些药品。
<其他抗肿瘤剂>
作为本发明的药品的有效成分,在不阻碍作为本发明的药品的效果的范围内,除了所述抗CAPRIN-1抗体和任意的拓扑异构酶I抑制剂之外,还可以包含文献等中公知的抗肿瘤剂。作为公知的抗肿瘤剂不特别限制,作为具体例,包含紫杉醇、多柔比星、柔红霉素、环磷酰胺、甲氨蝶呤、5-氟尿嘧啶、噻替哌、白消安、英丙舒凡、哌泊舒凡、benzodopa、卡波醌、meturedopa、uredopa、六甲蜜胺(altretamine)、三亚乙基三聚氰胺、三亚乙基磷酰胺、三亚乙基硫代磷酰胺(triethilenethiophosphoramide)、三羟甲基三聚氰胺(trimethylolomelamine)、布拉他辛、布拉他辛酮、苔藓虫素、海绵多聚乙酰(callystatin)、cryptophycin1、cryptophycin8、海兔毒素(dolastatin)、倍癌霉素(duocarmycin)、艾榴塞洛素(eleutherobin)、水鬼蕉碱(pancratistatin)、匍枝珊瑚醇(sarcodictyin)、spongistatin、苯丁酸氮芥、萘氮芥(chlornaphazine)、氯磷酰胺(cholophosphamide)、雌莫司汀、异环磷酰胺、甲氮芥、盐酸甲氧氮芥、美法仑、新氮芥(novembichin)、苯芥胆甾醇(phenesterine)、泼尼莫司汀(prednimustine)、曲磷胺(trofosfamide)、乌拉莫司汀、卡莫司汀、氯乙链脲菌素(chlorozotocin)、福莫司汀(fotemustine)、洛莫司汀、尼莫司汀、雷莫司汀、卡奇霉素(calicheamicin)、达内霉素(dynemicin)、氯屈膦酸、埃斯培拉霉素(esperamicin)、阿克拉霉素、放线菌素、安曲霉素(authramycin)、重氮丝氨酸、博来霉素、放线菌素C(cactinomycin)、卡柔比星(carabicin)、洋红霉素、嗜癌菌素(carzinophilin)、色霉素、更生霉素、detorbicin、6-重氮基-5-氧代-L-正亮氨酸、阿霉素(adriamycin)、表柔比星、依索比星、伊达比星、麻西罗霉素(marcellomycin)、丝裂霉素C、霉酚酸(mycophenolic acid)、诺加霉素(nogalamycin)、橄榄霉素(olivomycins)、培洛霉素、甲基丝裂霉素(potfiromycin)、嘌呤霉素、三铁阿霉素(quelamycin)、罗多比星(rodorubicin)、链黑菌素、链佐星、杀结核菌素(tubercidin)、乌苯美司、净司他丁(zinostatin)、佐柔比星(zorubicin)、二甲叶酸(denopterin)、蝶罗呤(pteropterin)、三甲曲沙(trimetrexate)、氟达拉滨(fludarabine)、6-巯嘌呤、硫咪嘌呤、硫鸟嘌呤、安西他滨、阿扎胞苷(azacitidine)、6-氮杂尿苷(azauridine)、卡莫氟、阿糖胞苷、二脱氧尿苷、去氧氟尿苷、依诺他滨(enocitabine)、氟尿苷(floxuridine);雄激素类、例如卡普睾酮(calusterone)、屈他雄酮丙酸酯、环硫雄醇、美雄烷、睾内酮(testolactone)、氨鲁米特、米托坦、曲洛司坦、亚叶酸(frolinic acid)、醋葡醛内酯、醛磷酰胺糖苷、氨基乙酰丙酸、恩尿嘧啶(eniluracil)、安吖啶(amsacrine)、阿莫司汀(bestrabucil)、比生群(bisantrene)、依达曲沙(edatraxate)、defofamine、秋水仙胺(demecolcine)、地吖醌(diaziquone)、依氟鸟氨酸(elfornithine)、依利醋铵(elliptinium)、埃博霉素(epothilone)、依托格鲁(etoglucid)、香茹多糖、氯尼达明(lonidamine)、美登素(maytansine)、安丝菌素(ansamitocine)、米托胍腙(mitoguazone)、米托蒽醌、mopidanmol、二胺硝吖啶nitraerine、喷司他丁、蛋氨氮芥(phenamet)、吡柔比星、洛索蒽醌(losoxantrone)、足叶草酸(podophyllinic acid)、2-乙基酰肼、甲苄肼、雷佐生(razoxane)、根瘤菌素(rhizoxin)、西佐喃、锗螺胺(spirogermanium)、细交链孢菌酮酸(tenuazonic acid)、三乙撑亚胺苯醌(triaziquone)、杆孢菌素(roridine)A、蛇形菌素(anguidine)、聚氨酯、长春地辛、达卡巴嗪、甘露醇氮芥(mannomustine)、二溴甘露醇、二溴卫矛醇(mitolactol)、哌泊溴烷(pipobroman)、gacytosine、多西他赛、瘤可宁、吉西他滨(gemcitabine)、6-硫鸟嘌呤、巯嘌呤、顺铂、奥沙利铂、卡波铂、长春碱、足叶乙甙、异环磷酰胺、米托葸醌、长春新碱、长春瑞滨、诺消灵(novantrone)、替尼泊苷、依达曲沙(edatrexate)、道诺霉素、氨蝶呤、希罗达(xeloda)、伊班膦酸盐(ibandronate)、二氟甲基鸟氨酸(DMFO)、视黄酸、卡培他滨(capecitabine)、以及它们的药学上可接受的盐或衍生物。
<本发明的抗肿瘤效果>
本发明的抗CAPRIN-1抗体与拓扑异构酶I抑制剂的组合在体内(in vivo)具有细胞毒活性。由此本发明的抗肿瘤效果可以通过调查对癌的细胞毒活性而获知。细胞毒活性可以通过对具有癌的生物体施与抗CAPRIN-1和拓扑异构酶I抑制剂,测量施与后的肿瘤的大小,经时地调查癌的大小来评价。另外,本发明的抗肿瘤效果也可以通过调查生存率来评价。另外,也可以通过调查细胞因子或趋化因子的产生能来评价。本发明中由抗CAPRIN-1抗体与拓扑异构酶I抑制剂的组合产生的抗肿瘤效果进一步可以通过调查癌的预防、转移的预防或复发的预防来获知。
本发明中使用的抗CAPRIN-1抗体与癌细胞表面上的CAPRIN-1蛋白质的结合亲和性越高,越可以期待更强的抗肿瘤效果。期望结合常数(亲和常数)Ka(kon/koff)优选为至少107M-1、至少108M-1、至少5×108M-1、至少109M-1、至少5×109M-1、至少1010M-1、至少5×1010M-1、至少1011M-1、至少5×1011M-1、至少1012M-1、或至少1013M-1
本发明中使用的抗CAPRIN-1抗体与CAPRIN-1结合的能力可以利用使用了例如ELISA法、蛋白质印迹法、免疫荧光和流式细胞仪法等的结合检验来特定。
本发明中的抗CAPRIN-1抗体与拓扑异构酶I抑制剂的组合向癌生物体内的施与如前所述与单独的抗CAPRIN-1抗体相比抗肿瘤效果增强,其增强率优选为30%以上、更优选为40%以上、进一步优选为50%以上、进一步更优选为55%以上、进一步更优选为60%以上、进一步更优选为65%以上、最优选为70%以上。本发明中的抗CAPRIN-1抗体与拓扑异构酶I抑制剂的组合施与相对于抗CAPRIN-1抗体单独施与的抗肿瘤效果的增强率,可以通过分别将有效量在相同条件下施与荷癌小鼠,比较施与开始后第7天以后的肿瘤体积来计算。
<用于癌的治疗和/或预防的药品>
本发明的药品以癌的治疗和/或预防为目的。成为本发明的药品的靶标的癌,只要是表达CAPRIN-1蛋白质的癌(细胞)就没有特别限定。
本说明书中使用的“治疗”是指基于前述的抗肿瘤效果的癌的治疗。另外,本说明书中使用的“预防”不仅指癌的发生的预防,还指癌的转移或复发的预防。
本说明书中使用的“肿瘤”和“癌”这样的术语是指恶性新生物,可以互换使用。
作为在本发明中成为对象的癌,只要是在细胞膜表面上表达CAPRIN-1蛋白质的癌就可以是任何癌。优选为卵巢癌、胆管癌、乳癌、肾癌、胰癌、大肠癌、黑素瘤(包括术后的黑素瘤)、肺癌(包括非小细胞肺癌、小细胞肺癌)、肾细胞癌、霍奇金淋巴瘤、头颈癌、胃癌、间皮癌(包括恶性胸膜间皮瘤)、结肠/直肠癌(例如具有MSI-high的结肠/直肠癌)、食道癌、食管胃结合部癌、肝细胞癌、胶质母细胞瘤、尿路上皮癌、膀胱癌、子宫癌(包括子宫颈癌、子宫体癌)、原发性中枢神经系统淋巴瘤、原发性睾丸淋巴瘤、胆道癌、脑肿瘤、前列腺癌、白血病、淋巴瘤、肝癌、肉瘤、纤维肉瘤、肥大细胞瘤、肾上腺皮质癌、尤因肉瘤、多发性骨髓瘤、睾丸癌、甲状腺癌、基底细胞癌、佩吉特病或皮肤癌。另外,上述这些癌可以是原发癌、转移性癌、转移了的癌或复发了的癌、术后的癌、或不能切除的癌。此外,黑素瘤经常与恶性黑素瘤或恶性黑色素瘤(malignant melanoma)同义地使用。
此外,作为在本发明中成为对象的癌,可列举对已知的治疗法具有耐性的癌。具有耐性的癌可以是具有任何治疗历史的患者来源的癌,不特别限定,例如,对于有利用铂类制剂或5-FU的治疗史的患者来源的癌,是施与后具有耐性的癌、转移了的癌或复发了的癌。
所述癌更具体地包含例如,鲍温病、黑色素瘤、鳞状细胞癌、乳房外佩吉特病、蕈样真菌病、Sezary综合征、皮肤T/NK细胞淋巴瘤、仅皮肤有病变的T细胞白血病/淋巴瘤、皮肤B细胞淋巴瘤(惰性组)、皮肤T细胞淋巴乳腺癌、复合型乳腺癌、乳腺恶性混合肿瘤、乳管内乳头状腺癌、肺腺癌、鳞状细胞癌、小细胞癌、大细胞癌、作为神经上皮组织性肿瘤的神经胶质瘤、成胶质细胞瘤、成神经细胞瘤、室管膜瘤、神经元肿瘤、胎儿型的神经外胚层肿瘤、神经鞘瘤、纤维神经瘤、脑脊膜瘤、慢性淋巴细胞白血病、淋巴瘤、消化道淋巴瘤、消化器官淋巴瘤、小~中细胞型淋巴瘤、盲肠癌、升结肠癌、降结肠癌、横结肠癌、乙状结肠癌、直肠癌、卵巢上皮癌、胚细胞瘤、间质细胞瘤、胰管癌、浸润性胰管癌、胰癌的腺癌、腺泡细胞癌、腺扁平上皮癌、巨细胞瘤、胰管内乳头粘液性肿瘤、粘液性囊腺癌、胰母细胞瘤、胰头细胞瘤、Frants肿瘤、浆液性囊腺癌、固体乳头状癌、胃泌素瘤、胰高血糖素瘤、胰岛素瘤、多发性内分泌腺瘤综合症1(Wermer综合症)、非功能性胰岛细胞瘤、生长激素抑制素瘤、VIP产生瘤、子宫颈癌、子宫体癌、纤维肉瘤、骨·关节肉瘤、尤文肉瘤、肾母细胞瘤(Wilms’tumor)、肝母细胞瘤、软组织肉瘤、急性白血病、慢性白血病、脊髓肿瘤、软组织恶性肿瘤、畸胎癌肿瘤、头颈癌包括下咽癌、中咽癌、舌癌、上咽癌、口腔癌、口唇癌、鼻窦癌、喉癌、肾盂输尿管癌、膀胱癌、尿道癌、精巢肿瘤、恶性胸膜间皮瘤、恶性骨肿瘤、子宫体癌(术后的化疗、转移复发时化疗)、儿童恶性实体肿瘤(横纹肌肉瘤、成神经细胞瘤、肝母细胞瘤、成神经细胞瘤、肾母细胞瘤、视网膜母细胞瘤、中枢神经系统胚胎细胞肿瘤、尤文肉瘤家族肿瘤)、浆液性肿瘤(包括浆液性边界恶性肿瘤(SBT))、粘液性肿瘤、表层上皮性边界恶性肿瘤、间质性边界恶性肿瘤等,但不限于这些。另外包含以上述癌为原发的能够触诊的癌、存在于皮下的癌、存在于皮内的癌、浅表性的癌、存在于真皮的癌或存在于非实体器官的癌、渐进性的癌。另外包含以上述癌为原发、通过转移或复发而能够触诊的癌、存在于皮下的癌、存在于皮内的癌、浅表性的癌、存在于真皮的癌或存在于非实体器官的癌。
另外,成为对象的优选的受试者(患者)是哺乳动物,例如是包含灵长类、宠物、家畜类、竞技用动物等的哺乳动物,特别优选是人、犬和猫。
本发明的药品可以利用本领域技术人员公知的方法进行制剂化。本发明的药品可以以例如在水或除水以外的药学上容许的液体中的无菌性溶液、或悬浮液剂的注射剂的形式非经口地使用。在本发明的药品中,也可以对每种制剂或药物组合物将其有效成分(抗CAPRIN-1抗体和拓扑异构酶I抑制剂)与例如与药理学上容许的载体或介质、具体来说为灭菌水、生理盐水、等渗液、缓冲剂(缓冲液等)、植物油、油性油、氧化防止剂、助溶剂、乳化剂、悬浮剂、表面活性剂、稳定剂、芳香剂、赋形剂、结合剂等适当组合,优选可以通过以一般认为的制药实施所要求的单位用量方式与它们混和来进行制剂化。这些制剂中的有效成分量,是可得到所指示的范围的适当的用量那样的量。
用于注射的无菌组合物可以使用注射用蒸馏水这样的媒介物,按照通常的制剂实施来处方。作为注射用的水溶液,可以列举例如,生理盐水、含有葡萄糖和/或其他辅助剂、例如D-山梨糖醇、D-甘露糖、D-甘露醇、氯化钠的等渗液,也可以与适当的溶解助剂、例如醇、具体为乙醇、多元醇例如丙二醇、聚乙二醇、非离子性表面活性剂例如聚山梨醇酯80(TM)、HCO-60联合使用。作为油性液可以列举芝麻油、大豆油,其也可以与作为溶解助剂的苯甲酸苄酯、苄醇联合使用。另外,还可以与缓冲剂例如磷酸盐缓冲液、乙酸钠缓冲液、镇痛剂例如盐酸普鲁卡因、稳定剂例如苄醇、苯酚、抗氧化剂配合。制备的注射液通常填充到适当的安瓿中即可。
施与为经口或非经口,优选非经口施与,具体来说,可以列举注射剂型、经鼻施与剂型、经肺施与剂型、经皮施与型等。作为注射剂型的例子,可以通过例如静脉内注射、肌肉内注射、腹腔内注射、皮下注射、肿瘤内注射等全身或局部性地施与。作为经皮施与型的例子,例如为被称为涂布剂或外用药的剂型。作为外用药,可列举固体制剂、液剂、喷雾剂、软膏剂、乳膏剂、或凝胶剂。
另外,可以根据患者的年龄、体重、性别、症状等选择适当的施与方法。作为含有抗CAPRIN-1抗体和拓扑异构酶I抑制剂的至少一者的药物组合物的施与量,以各有效成分的量记,例如,可以在一次每1kg体重为0.0001mg至1000mg的范围中选择。或者例如可以在每个患者0.001~100000mg/个体的范围、或例如患者的每1kg体重1mg至30mg中选择施与量,但未必限于这些数值。施与量、施与方法根据患者的体重、年龄、性别、症状等不同而变化,只要是本领域技术人员就可以适当选择。
<施与方法>
利用本发明的用于癌的治疗和/或预防的药品的癌的治疗和/或预防,除了作为前述的药品施与之外,包含各种形式。例如,本发明的药品的各有效成分可以同时或按顺序逐个施与。作为具体例,可以以到约3周的时间间隔内、即在从施与第1有效成分之后开始到约3周施与第2有效成分。此时,可以接着外科处置之后而实施,也可以在第1药剂与第2药剂的施与之间实施外科处置。另外,可以将本发明的癌的治疗和/或预防剂按照多个施与循环进行施与。例如,在实施本发明的癌的治疗和/或预防剂的各有效成分的同时施与的情况下,将包含双方的有效成分的药物组合物以约2天至约3周为1循环进行施与。然后,按照负责的医师的判断,根据需要可以将该治疗循环重复。同样地在计划按照顺序的处方时,分别将各个药剂的施与期间调整为相同期间。循环之间的间隔可以在0~2个月变化。本发明的癌的治疗和/或预防剂的各有效成分的施与量可以与药物组合物中的各有效成分的施与量同样地设定。
<制药试剂盒>
本发明的癌的治疗和/或预防用的药品可以是制药试剂盒的形态。制药试剂盒是指在治疗和/或预防癌的方法中,用于将有效成分以单个的药物组合物的形态使用的包,该包包含用于施与各有效成分的使用说明书。制药试剂盒中包含的癌的治疗和/或预防用的上述药物组合物的各有效成分,可以是以能够将各有效成分一起或分别施与的方式分别如上所述制剂化而成的药物组合物的形态。另外,制药试剂盒为了能够将各有效成分按照上述施与方法施与,包含对于1次或多次的用量为充分的量的有效成分。
基于上面具体说明的内容,本发明进一步提供包括将本发明的上述药品施与怀疑具有癌的受检者的用于癌的治疗和/或预防的方法。另外,在其实施方式中,上述药品所含的抗体或其片段和抗肿瘤剂可以同时或分别施与上述受检者。
实施例
以下,基于实施例具体地说明本发明,但本发明的范围不受这些具体例限制。
(实施例1)抗CAPRIN-1抗体的制作
本发明中使用与CAPRIN-1蛋白质具有免疫反应性的抗CAPRIN-1抗体,使用如下制作的抗体。
(多克隆抗体)
将按照WO2010/016526的实施例3制作的人CAPRIN-1重组蛋白质1mg与等体积的氟氏不完全佐剂(IFA)溶液混合,将其每隔2周在兔的皮下进行施与,共施与4次。然后采集血液,获得包含多克隆抗体的抗血清。进一步将该抗血清使用蛋白G载体(GEヘルスケアバイオサイエンス社制)纯化,替换为PBS(-),得到针对CAPRIN-1蛋白质的多克隆抗体(抗CAPRIN-1多克隆抗体#1)。
(单克隆抗体)
将按照WO2010/016526的实施例3制作的人CAPRIN-1重组蛋白质100μg与等量的MPL+TDM佐剂(シグマ社制)混合,将此作为每1只小鼠的抗原溶液。将抗原溶液施与到6周龄的Balb/c小鼠(日本SLC社制)的腹腔内后,每1周进一步进行施与3次和24次,从而完成免疫。从最后的免疫起3天后摘出的各自的脾脏用灭菌后的2枚载玻片夹持磨碎,将使用PBS(-)(日水社制)洗涤、以1500rpm离心10分钟并除去上清的操作重复3次,获得脾脏细胞。将所得的脾脏细胞与小鼠骨髓瘤细胞SP2/0(从ATCC购入)以10:1的比率混和,在其中加入将加温至37℃的包含10%FBS的RPMI1640培养基200μL和PEG1500(ベーリンガー社制)800μL混合而制备的PEG溶液,并静置5分钟,从而进行细胞融合。以1700转/分钟离心5分钟,除去上清,然后用加入了2%当量的Gibco社制的HAT溶液的含15%FBS的RPMI1640培养基(HAT选择培养基)150ml悬浮细胞,以96孔板(ヌンク社制)的每1孔各100μl接种于15块板中。以7天、37℃、5%CO2的条件培养,从而得到脾脏细胞与骨髓瘤细胞融合而成的杂交瘤。以由制作的杂交瘤所产生的抗体的对CAPRIN-1蛋白质的结合亲和性为指标筛选杂交瘤。将CAPRIN-1蛋白质溶液1μg/ml在96孔板每1孔中添加100μL,在4℃静置18小时。将各孔用PBS-T洗涤3次后,在每1孔中添加0.5%牛血清白蛋白(BSA)溶液(シグマ社制)400μL,在室温静置3小时。除去溶液,对每1孔用400μL的PBS-T洗涤孔3次后,在每1孔中添加上述所得的杂交瘤的各培养上清100μL,在室温静置2小时。用PBS-T洗涤各孔3次后,在每1孔中添加用PBS稀释至5000倍的HRP标记抗小鼠IgG(H+L)抗体(インビトロジェン社制)100μL,在室温静置1小时。用PBS-T洗涤孔3次后,在每1孔中添加TMB底物溶液(Thermo社制)100μl,并静置15~30分钟,从而进行显色反应。显色后,在每1孔中添加1N硫酸100μl使反应停止,使用吸光度计测定450nm和595nm的吸光度值。其结果是,筛选出了多个产生吸光度值高的抗体的杂交瘤。将筛选出的杂交瘤以96孔板每1孔0.5个的方式添加到板中进行培养。1周后,观察到在孔中形成单个集落的杂交瘤。将这些孔的细胞进行进一步培养,以由克隆化的杂交瘤产生的抗体对CAPRIN-1蛋白质的结合亲和性为指标筛选杂交瘤。将CAPRIN-1蛋白质溶液1μg/ml在96孔板的每1孔中添加100μL,在4℃静置18小时。用PBS-T洗涤各孔3次后,在每1孔中添加0.5%BSA溶液400μL,并在室温静置3小时。除去溶液,对每1孔用400μL的PBS-T洗涤孔3次后,在每1孔中添加上述所得的杂交瘤的各培养上清100μL,在室温静置2小时。用PBS-T洗涤各孔3次后,在每1孔中添加用PBS稀释至5000倍的HRP标记抗小鼠IgG(H+L)抗体(インビトロジェン社制)100μL并在室温静置1小时。用PBS-T洗涤孔3次后,在每1孔中添加TMB底物溶液(Thermo社制)100μL,并静置15~30分钟,从而进行显色反应。显色后,在每1孔中添加1N硫酸100μL使反应停止,使用吸光度计测定450nm和595nm的吸光度值。其结果是,得到了多个对CAPRIN-1蛋白质显示反应性的小鼠单克隆抗体。
进而通过流式细胞仪法确认对人癌细胞的反应性,所述人癌细胞是已经确认了在细胞膜表面表达CAPRIN-1蛋白质的细胞。作为阴性对照使用不与所述癌细胞显示反应性的小鼠IgG对照抗体。确认的结果是,对所述癌细胞,得到了数个与小鼠IgG对照抗体相比荧光强度强、与在细胞膜表面表达CAPRIN-1的上述癌细胞的细胞膜表面强烈地反应的单克隆抗体。从中作为与CAPRIN-1蛋白质显示反应性的单克隆抗体,筛选出了作为WO2013/125630中记载的针对CAPRIN-1的单克隆抗体的所述(ab)的包含序列号114所示的重链可变区的氨基酸序列、和序列号115所示的轻链可变区的氨基酸序列的抗体。
特定上述筛选出的抗体的重链可变区的CDR1~3,以能够表达框架区包含人抗体的序列的重链可变区的方式设计碱基序列,将其插入到已经插入有人IgG1的重链恒定区的哺乳类表达用载体中。同样地,特定轻链可变区的CDR1~3,以能够表达框架区包含人抗体的序列的轻链可变区的方式设计碱基序列,将其插入到已经插入有人IgG1的轻链恒定区的哺乳类表达用载体中。将上述2种重组表达载体按照常规方法导入哺乳类细胞,获得包含针对CAPRIN-1的人源化单克隆抗体#1(人源化抗体#1)的培养上清。
将所得的包含人源化抗CAPRIN-1单克隆抗体#1的培养上清按照常规方法使用Hitrap Protein A SepharoseFF(GEヘルスケア社制)进行纯化,替换成PBS(-),用0.22μm的过滤器(ミリポア社制)进行过滤,从而制备。
上述抗CAPRIN-1抗体对CAPRIN-1蛋白质的特异反应性通过将CAPRIN-1蛋白质在平板上固相化使用ELISA法进行检测来确认。
此外,使用上述抗CAPRIN-1抗体通过流式细胞仪法调查与未进行细胞膜的透过处理的癌细胞的反应性,从而如以下实施例所示,确认了CAPRIN-1的一部分在癌细胞的细胞膜表面表达。
通过流式细胞仪法确认了,对作为确认了CAPRIN-1的基因的表达的人癌细胞的乳癌细胞(BT-474)、大肠癌细胞(HT-29)、肺癌细胞(QG56、H1650)、胃癌细胞(NCI-N87)、子宫癌细胞(HEC-1-A)、前列腺癌细胞(22Rv1)、胰脏癌细胞(Panc10.5)、肝脏癌细胞(Hep3B)、卵巢癌细胞(SKOV3)、肾癌细胞(Caki-2)、脑肿瘤细胞(U-87MG)、膀胱癌细胞(T24)、食道癌细胞(OE33)、白血病细胞(OCI-AML5)、淋巴瘤细胞(Ramos)、胆囊癌细胞(TGBC14TKB)、纤维肉瘤细胞(HT-1080)、黑素瘤细胞(G-361)、确认了CAPRIN-1的基因的表达的小鼠肾癌细胞(Renca)、小鼠乳癌细胞(4T1)的任意癌细胞,人源化抗体#1都比对作为阴性对照的癌细胞不显示反应性的人IgG对照抗体以及兔IgG抗体荧光强度强,确认了与CAPRIN-1表达的上述癌细胞的细胞膜表面强烈地反应.
同样地,对于WO2010/016526、WO2011/096517、WO2011/096528、WO2011/096519、WO2011/096533、WO2011/096534、WO2011/096535、WO2013/018886、WO2013/018894、WO2013/018892、WO2013/018891、WO2013/018889、WO2013/018883、WO2013/125636、WO2013/125654、WO2013/125640、WO2013/147169、WO2013/147176以及WO2015/020212中记载的所述(a)~(aa)和(ac)~(al)的各抗CAPRIN-1抗体,也同样地确认了与上述癌细胞膜表面强烈地反应。
(实施例2)由抗CAPRIN-1抗体与拓扑替康的联合使用产生的抗肿瘤效果
对于实施例1中制作的抗CAPRIN-1抗体(抗CAPRIN-1人源化抗体#1)与拓扑替康的联合使用产生的荷癌小鼠生物体内的抗肿瘤效果进行评价。
具体地,使用将表达CAPRIN-1蛋白质的人来源的癌细胞移植到皮下而得的NOD-SCID小鼠,研究本发明中的由抗CAPRIN-1抗体与拓扑替康的联合使用产生的抗肿瘤效果。对每1只小鼠,将2×107个人乳癌细胞BT474与Matrigel(基质胶)(SIGMA)混合而移植到皮下,使其成长到肿瘤为约154~155mm3,从而制作荷癌小鼠。BT474在细胞膜表面表达CAPRIN-1蛋白质,是确认了实施例1中制作的抗CAPRIN-1抗体与位于细胞膜表面的CAPRIN-1的一部分反应的癌细胞。分别对8只上述荷癌小鼠的尾静脉各以10mg/kg施与实施例1中制作的抗CAPRIN-1抗体,一周各施与1次,共计施与4次。对相同的小鼠,每4天各施与低用量(3mg/kg)或高用量(10mg/kg)的拓扑替康1次,共计施与4次。
作为比较对照组,对荷癌小鼠将与上述相同的抗CAPRIN-1抗体以等量一周施与各1次。进而作为比较对照组,对别的荷癌小鼠个体将低用量(3mg/kg)或高用量(10mg/kg)的拓扑替康以同样的施与间隔进行施与。进而将无治疗组的荷癌小鼠作为阴性对照。开始施与后,经时地使用游标卡尺测量荷癌小鼠的癌的大小,肿瘤体积按照常规方法,通过算式:(癌的长径的长度)×(癌的短径的长度)2×0.5对每个个体计算出施与组的平均值。
评价的结果是,在药剂施与结束约2周后(荷癌后第56天),在以阴性对照的肿瘤体积为100%时,作为比较对象组的实施例1中制作的抗CAPRIN-1人源化抗体#1施与组的肿瘤体积为38%,拓扑替康低用量施与组中为33%,以及拓扑替康高用量施与组中为16%,肿瘤体积比施与开始时增大。另一方面,联合施与了实施例1中制作的人源化抗体#1和拓扑替康低用量的组的肿瘤体积为6%,以及联合施与了实施例1中制作的人源化抗体#1和拓扑替康高用量的组的肿瘤体积为0%(在全部个体中肿瘤退缩),比施与开始时缩小。
同样地确认了,对于WO2010/016526、WO2011/096517、WO2011/096528、WO2011/096519、WO2011/096533、WO2011/096534、WO2011/096535、WO2013/018886、WO2013/018894、WO2013/018892、WO2013/018891、WO2013/018889、WO2013/018883、WO2013/125636、WO2013/125654、WO2013/125640、WO2013/147169、WO2013/147176以及WO2015/020212记载的所述(a)~(aa)和(ac)~(al)的各抗CAPRIN-1抗体,通过组合拓扑替康而施与,从而与单独施与抗CAPRIN-1抗体的情况、以及单独施与拓扑替康的情况相比,具有显著强的抗肿瘤效果。
本评价的结果显示,通过组合施与抗CAPRIN-1抗体与拓扑替康,与单独施与抗CAPRIN-1抗体的情况、以及单独施与拓扑替康的情况相比,具有显著强的抗肿瘤效果。
(比较例1)由抗CAPRIN-1抗体与其他拓扑异构酶抑制剂的联合使用产生的抗肿瘤效果
接着,对于实施例1中制作的抗CAPRIN-1抗体(抗CAPRIN-1人源化抗体#1)与作为不同于拓扑替康的别的拓扑异构酶抑制剂(拓扑异构酶II抑制剂)的依托泊苷的联合使用产生的荷癌小鼠生物体内的抗肿瘤效果进行评价。
具体地,使用将表达CAPRIN-1蛋白质的人来源的癌细胞移植到皮下而得的NOD-SCID小鼠,研究由抗CAPRIN-1抗体与依托泊苷的联合使用产生的抗肿瘤效果。对每1只小鼠,将2×107个人乳癌细胞BT474与Matrigel(基质胶)(SIGMA)混合而移植到皮下,使其成长到肿瘤为约190~192mm3,从而制作荷癌小鼠。BT474在细胞膜表面表达CAPRIN-1蛋白质,是确认了实施例1中制作的抗CAPRIN-1抗体与位于细胞膜表面的CAPRIN-1的一部分反应的癌细胞。分别对8只上述荷癌小鼠的尾静脉各以10mg/kg施与实施例1中制作的抗CAPRIN-1抗体,一周各施与1次,共计施与4次。对相同的小鼠,每4天各施与低用量(5mg/kg)或高用量(15mg/kg)的依托泊苷1次,共计施与4次。
作为比较对照组,对荷癌小鼠将与上述相同的抗CAPRIN-1抗体以等量一周施与各1次。进而作为比较对照组,对别的荷癌小鼠个体将低用量(5mg/kg)或高用量(15mg/kg)的依托泊苷以同样的施与间隔进行施与。进而将无治疗组的荷癌小鼠作为阴性对照。开始施与后,经时地使用游标卡尺测量荷癌小鼠的癌的大小,肿瘤体积按照常规方法,通过算式:(癌的长径的长度)×(癌的短径的长度)2×0.5对每个个体计算出施与组的平均值。
评价的结果是,在药剂施与结束约2周后(荷癌后第55天),在以阴性对照的肿瘤体积为100%时,作为比较对象组的实施例1中制作的抗CAPRIN-1人源化抗体#1施与组的肿瘤体积为35%,依托泊苷低用量施与组中为92%,依托泊苷高用量施与组中为79%,联合施与了实施例1中制作的人源化抗体#1和依托泊苷低用量的组的肿瘤体积为18%,以及联合施与了实施例1中制作的人源化抗体#1和依托泊苷高用量的组的肿瘤体积为30%,在任意处置组中肿瘤体积比施与开始时增大。
与实施例2所示的由与拓扑替康的联合使用产生的抗肿瘤效果的评价结果相比,组合针对CAPRIN-1的抗体与依托泊苷而处置的情况下的抗肿瘤效果低,显示了在组合针对CAPRIN-1的抗体与作为拓扑异构酶I抑制剂的拓扑替康而处置的情况下,具有显著强的协同的抗肿瘤效果。
序列表
<110> 东丽株式会社
<120> 东丽株式会社
<130> 21B0436
<160> 309
<170> PatentIn 版本 3.5
<210> 1
<211> 5562
<212> DNA
<213> 人(Homo sapiens)
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<222> (190)..(2319)
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tattgtctca ttctgacttc atggagaatt aatcccacct ttaagcaaag gctactaagt 3849
taatggtatt ttctgtgcag aaattaaatt ttattttcag catttagccc aggaattctt 3909
ccagtaggtg ctcagctatt taaaaacaaa actattctca aacattcatc attagacaac 3969
tggagttttt gctggttttg taacctacca aaatggatag gctgttgaac attccacatt 4029
caaaagtttt gtagggtggt gggaaatggg ggatcttcaa tgtttatttt aaaataaaat 4089
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catctgcctg ggatgtacca caaccatatg ttacctgtat cttaggggaa tggataaaat 4269
atttgtggtt tactgggtaa tccctagatg atgtatgctt gcagtcctat ataaaactaa 4329
atttgctatc tgtgtagaaa ataatttcat gacatttaca atcaggactg aagtaagttc 4389
ttcacacagt gacctctgaa tcagtttcag agaagggatg ggggagaaaa tgccttctag 4449
gttttgaact tctatgcatt agtgcagatg ttgtgaatgt gtaaaggtgt tcatagtttg 4509
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tatttttaaa ggggtgcctc attatggggc agagaacttt tcaataagtc tcattaagat 4689
ctgaatcttg gttctaagca ttctgtataa tatgtgattg cttgtcctag ctgcagaagg 4749
ccttttgttt ggtcaaatgc atattttagc agagtttcaa ggaaatgatt gtcacacatg 4809
tcactgtagc ctcttggtgt agcaagctca catacaaaat acttttgtat atgcataata 4869
taaatcatct catgtggata tgaaacttct tttttaaaac ttaaaaaggt agaatgttat 4929
tgattacctt gattagggca gttttatttc cagatcctaa taattcctaa aaaatatgga 4989
aaagtttttt ttcaatcatt gtaccttgat attaaaacaa atatccttta agtatttcta 5049
atcagttagc ttctacagtt cttttgtctc cttttatatg cagctcttac gtgggagact 5109
tttccactta aaggagacat agaatgtgtg cttattctca gaaggttcat taactgaggt 5169
gatgagttaa caactagttg agcagtcagc ttcctaagtg ttttaggaca tttgttcatt 5229
atattttccg tcatataact agaggaagtg gaatgcagat aagtgccgaa ttcaaaccct 5289
tcattttatg tttaagctcc tgaatctgca ttccacttgg gttgttttta agcattctaa 5349
attttagttg attataagtt agatttcaca gaatcagtat tgcccttgat cttgtccttt 5409
ttatggagtt aacggggagg aagacccctc aggaaaacga aagtaaattg ttaaggctca 5469
tcttcatacc tttttccatt ttgaatccta caaaaatact gcaaaagact agtgaatgtt 5529
taaaattaca ctagattaaa taatatgaaa gtc 5562
<210> 2
<211> 709
<212> PRT
<213> 人(Homo sapiens)
<400> 2
Met Pro Ser Ala Thr Ser His Ser Gly Ser Gly Ser Lys Ser Ser Gly
1 5 10 15
Pro Pro Pro Pro Ser Gly Ser Ser Gly Ser Glu Ala Ala Ala Gly Ala
20 25 30
Gly Ala Ala Ala Pro Ala Ser Gln His Pro Ala Thr Gly Thr Gly Ala
35 40 45
Val Gln Thr Glu Ala Met Lys Gln Ile Leu Gly Val Ile Asp Lys Lys
50 55 60
Leu Arg Asn Leu Glu Lys Lys Lys Gly Lys Leu Asp Asp Tyr Gln Glu
65 70 75 80
Arg Met Asn Lys Gly Glu Arg Leu Asn Gln Asp Gln Leu Asp Ala Val
85 90 95
Ser Lys Tyr Gln Glu Val Thr Asn Asn Leu Glu Phe Ala Lys Glu Leu
100 105 110
Gln Arg Ser Phe Met Ala Leu Ser Gln Asp Ile Gln Lys Thr Ile Lys
115 120 125
Lys Thr Ala Arg Arg Glu Gln Leu Met Arg Glu Glu Ala Glu Gln Lys
130 135 140
Arg Leu Lys Thr Val Leu Glu Leu Gln Tyr Val Leu Asp Lys Leu Gly
145 150 155 160
Asp Asp Glu Val Arg Thr Asp Leu Lys Gln Gly Leu Asn Gly Val Pro
165 170 175
Ile Leu Ser Glu Glu Glu Leu Ser Leu Leu Asp Glu Phe Tyr Lys Leu
180 185 190
Val Asp Pro Glu Arg Asp Met Ser Leu Arg Leu Asn Glu Gln Tyr Glu
195 200 205
His Ala Ser Ile His Leu Trp Asp Leu Leu Glu Gly Lys Glu Lys Pro
210 215 220
Val Cys Gly Thr Thr Tyr Lys Val Leu Lys Glu Ile Val Glu Arg Val
225 230 235 240
Phe Gln Ser Asn Tyr Phe Asp Ser Thr His Asn His Gln Asn Gly Leu
245 250 255
Cys Glu Glu Glu Glu Ala Ala Ser Ala Pro Ala Val Glu Asp Gln Val
260 265 270
Pro Glu Ala Glu Pro Glu Pro Ala Glu Glu Tyr Thr Glu Gln Ser Glu
275 280 285
Val Glu Ser Thr Glu Tyr Val Asn Arg Gln Phe Met Ala Glu Thr Gln
290 295 300
Phe Thr Ser Gly Glu Lys Glu Gln Val Asp Glu Trp Thr Val Glu Thr
305 310 315 320
Val Glu Val Val Asn Ser Leu Gln Gln Gln Pro Gln Ala Ala Ser Pro
325 330 335
Ser Val Pro Glu Pro His Ser Leu Thr Pro Val Ala Gln Ala Asp Pro
340 345 350
Leu Val Arg Arg Gln Arg Val Gln Asp Leu Met Ala Gln Met Gln Gly
355 360 365
Pro Tyr Asn Phe Ile Gln Asp Ser Met Leu Asp Phe Glu Asn Gln Thr
370 375 380
Leu Asp Pro Ala Ile Val Ser Ala Gln Pro Met Asn Pro Thr Gln Asn
385 390 395 400
Met Asp Met Pro Gln Leu Val Cys Pro Pro Val His Ser Glu Ser Arg
405 410 415
Leu Ala Gln Pro Asn Gln Val Pro Val Gln Pro Glu Ala Thr Gln Val
420 425 430
Pro Leu Val Ser Ser Thr Ser Glu Gly Tyr Thr Ala Ser Gln Pro Leu
435 440 445
Tyr Gln Pro Ser His Ala Thr Glu Gln Arg Pro Gln Lys Glu Pro Ile
450 455 460
Asp Gln Ile Gln Ala Thr Ile Ser Leu Asn Thr Asp Gln Thr Thr Ala
465 470 475 480
Ser Ser Ser Leu Pro Ala Ala Ser Gln Pro Gln Val Phe Gln Ala Gly
485 490 495
Thr Ser Lys Pro Leu His Ser Ser Gly Ile Asn Val Asn Ala Ala Pro
500 505 510
Phe Gln Ser Met Gln Thr Val Phe Asn Met Asn Ala Pro Val Pro Pro
515 520 525
Val Asn Glu Pro Glu Thr Leu Lys Gln Gln Asn Gln Tyr Gln Ala Ser
530 535 540
Tyr Asn Gln Ser Phe Ser Ser Gln Pro His Gln Val Glu Gln Thr Glu
545 550 555 560
Leu Gln Gln Glu Gln Leu Gln Thr Val Val Gly Thr Tyr His Gly Ser
565 570 575
Pro Asp Gln Ser His Gln Val Thr Gly Asn His Gln Gln Pro Pro Gln
580 585 590
Gln Asn Thr Gly Phe Pro Arg Ser Asn Gln Pro Tyr Tyr Asn Ser Arg
595 600 605
Gly Val Ser Arg Gly Gly Ser Arg Gly Ala Arg Gly Leu Met Asn Gly
610 615 620
Tyr Arg Gly Pro Ala Asn Gly Phe Arg Gly Gly Tyr Asp Gly Tyr Arg
625 630 635 640
Pro Ser Phe Ser Asn Thr Pro Asn Ser Gly Tyr Thr Gln Ser Gln Phe
645 650 655
Ser Ala Pro Arg Asp Tyr Ser Gly Tyr Gln Arg Asp Gly Tyr Gln Gln
660 665 670
Asn Phe Lys Arg Gly Ser Gly Gln Ser Gly Pro Arg Gly Ala Pro Arg
675 680 685
Gly Arg Gly Gly Pro Pro Arg Pro Asn Arg Gly Met Pro Gln Met Asn
690 695 700
Thr Gln Gln Val Asn
705
<210> 3
<211> 3553
<212> DNA
<213> 人(Homo sapiens)
<220>
<221> CDS
<222> (190)..(2274)
<400> 3
cagagggctg ctggctggct aagtccctcc cgctcccggc tctcgcctca ctaggagcgg 60
ctctcggtgc agcgggacag ggcgaagcgg cctgcgccca cggagcgcgc gacactgccc 120
ggaagggacc gccacccttg ccccctcagc tgcccactcg tgatttccag cggcctccgc 180
gcgcgcacg atg ccc tcg gcc acc agc cac agc ggg agc ggc agc aag tcg 231
Met Pro Ser Ala Thr Ser His Ser Gly Ser Gly Ser Lys Ser
1 5 10
tcc gga ccg cca ccg ccg tcg ggt tcc tcc ggg agt gag gcg gcc gcg 279
Ser Gly Pro Pro Pro Pro Ser Gly Ser Ser Gly Ser Glu Ala Ala Ala
15 20 25 30
gga gcc ggg gcc gcc gcg ccg gct tct cag cac ccc gca acc ggc acc 327
Gly Ala Gly Ala Ala Ala Pro Ala Ser Gln His Pro Ala Thr Gly Thr
35 40 45
ggc gct gtc cag acc gag gcc atg aag cag att ctc ggg gtg atc gac 375
Gly Ala Val Gln Thr Glu Ala Met Lys Gln Ile Leu Gly Val Ile Asp
50 55 60
aag aaa ctt cgg aac ctg gag aag aaa aag ggt aag ctt gat gat tac 423
Lys Lys Leu Arg Asn Leu Glu Lys Lys Lys Gly Lys Leu Asp Asp Tyr
65 70 75
cag gaa cga atg aac aaa ggg gaa agg ctt aat caa gat cag ctg gat 471
Gln Glu Arg Met Asn Lys Gly Glu Arg Leu Asn Gln Asp Gln Leu Asp
80 85 90
gcc gtt tct aag tac cag gaa gtc aca aat aat ttg gag ttt gca aaa 519
Ala Val Ser Lys Tyr Gln Glu Val Thr Asn Asn Leu Glu Phe Ala Lys
95 100 105 110
gaa tta cag agg agt ttc atg gca cta agt caa gat att cag aaa aca 567
Glu Leu Gln Arg Ser Phe Met Ala Leu Ser Gln Asp Ile Gln Lys Thr
115 120 125
ata aag aag aca gca cgt cgg gag cag ctt atg aga gaa gaa gct gaa 615
Ile Lys Lys Thr Ala Arg Arg Glu Gln Leu Met Arg Glu Glu Ala Glu
130 135 140
cag aaa cgt tta aaa act gta ctt gag cta cag tat gtt ttg gac aaa 663
Gln Lys Arg Leu Lys Thr Val Leu Glu Leu Gln Tyr Val Leu Asp Lys
145 150 155
ttg gga gat gat gaa gtg cgg act gac ctg aaa caa ggt ttg aat gga 711
Leu Gly Asp Asp Glu Val Arg Thr Asp Leu Lys Gln Gly Leu Asn Gly
160 165 170
gtg cca ata ttg tcc gaa gag gag ttg tca ttg ttg gat gaa ttc tat 759
Val Pro Ile Leu Ser Glu Glu Glu Leu Ser Leu Leu Asp Glu Phe Tyr
175 180 185 190
aag cta gta gac cct gaa cgg gac atg agc ttg agg ttg aat gaa cag 807
Lys Leu Val Asp Pro Glu Arg Asp Met Ser Leu Arg Leu Asn Glu Gln
195 200 205
tat gaa cat gcc tcc att cac ctg tgg gac ctg ctg gaa ggg aag gaa 855
Tyr Glu His Ala Ser Ile His Leu Trp Asp Leu Leu Glu Gly Lys Glu
210 215 220
aaa cct gta tgt gga acc acc tat aaa gtt cta aag gaa att gtt gag 903
Lys Pro Val Cys Gly Thr Thr Tyr Lys Val Leu Lys Glu Ile Val Glu
225 230 235
cgt gtt ttt cag tca aac tac ttt gac agc acc cac aac cac cag aat 951
Arg Val Phe Gln Ser Asn Tyr Phe Asp Ser Thr His Asn His Gln Asn
240 245 250
ggg ctg tgt gag gaa gaa gag gca gcc tca gca cct gca gtt gaa gac 999
Gly Leu Cys Glu Glu Glu Glu Ala Ala Ser Ala Pro Ala Val Glu Asp
255 260 265 270
cag gta cct gaa gct gaa cct gag cca gca gaa gag tac act gag caa 1047
Gln Val Pro Glu Ala Glu Pro Glu Pro Ala Glu Glu Tyr Thr Glu Gln
275 280 285
agt gaa gtt gaa tca aca gag tat gta aat aga cag ttc atg gca gaa 1095
Ser Glu Val Glu Ser Thr Glu Tyr Val Asn Arg Gln Phe Met Ala Glu
290 295 300
aca cag ttc acc agt ggt gaa aag gag cag gta gat gag tgg aca gtt 1143
Thr Gln Phe Thr Ser Gly Glu Lys Glu Gln Val Asp Glu Trp Thr Val
305 310 315
gaa acg gtt gag gtg gta aat tca ctc cag cag caa cct cag gct gca 1191
Glu Thr Val Glu Val Val Asn Ser Leu Gln Gln Gln Pro Gln Ala Ala
320 325 330
tcc cct tca gta cca gag ccc cac tct ttg act cca gtg gct cag gca 1239
Ser Pro Ser Val Pro Glu Pro His Ser Leu Thr Pro Val Ala Gln Ala
335 340 345 350
gat ccc ctt gtg aga aga cag cga gta caa gac ctt atg gca caa atg 1287
Asp Pro Leu Val Arg Arg Gln Arg Val Gln Asp Leu Met Ala Gln Met
355 360 365
cag ggt ccc tat aat ttc ata cag gat tca atg ctg gat ttt gaa aat 1335
Gln Gly Pro Tyr Asn Phe Ile Gln Asp Ser Met Leu Asp Phe Glu Asn
370 375 380
cag aca ctt gat cct gcc att gta tct gca cag cct atg aat cca aca 1383
Gln Thr Leu Asp Pro Ala Ile Val Ser Ala Gln Pro Met Asn Pro Thr
385 390 395
caa aac atg gac atg ccc cag ctg gtt tgc cct cca gtt cat tct gaa 1431
Gln Asn Met Asp Met Pro Gln Leu Val Cys Pro Pro Val His Ser Glu
400 405 410
tct aga ctt gct cag cct aat caa gtt cct gta caa cca gaa gcg aca 1479
Ser Arg Leu Ala Gln Pro Asn Gln Val Pro Val Gln Pro Glu Ala Thr
415 420 425 430
cag gtt cct ttg gta tca tcc aca agt gag ggg tac aca gca tct caa 1527
Gln Val Pro Leu Val Ser Ser Thr Ser Glu Gly Tyr Thr Ala Ser Gln
435 440 445
ccc ttg tac cag cct tct cat gct aca gag caa cga cca cag aag gaa 1575
Pro Leu Tyr Gln Pro Ser His Ala Thr Glu Gln Arg Pro Gln Lys Glu
450 455 460
cca att gat cag att cag gca aca atc tct tta aat aca gac cag act 1623
Pro Ile Asp Gln Ile Gln Ala Thr Ile Ser Leu Asn Thr Asp Gln Thr
465 470 475
aca gca tca tca tcc ctt cct gct gcg tct cag cct caa gta ttt cag 1671
Thr Ala Ser Ser Ser Leu Pro Ala Ala Ser Gln Pro Gln Val Phe Gln
480 485 490
gct ggg aca agc aaa cct tta cat agc agt gga atc aat gta aat gca 1719
Ala Gly Thr Ser Lys Pro Leu His Ser Ser Gly Ile Asn Val Asn Ala
495 500 505 510
gct cca ttc caa tcc atg caa acg gtg ttc aat atg aat gcc cca gtt 1767
Ala Pro Phe Gln Ser Met Gln Thr Val Phe Asn Met Asn Ala Pro Val
515 520 525
cct cct gtt aat gaa cca gaa act tta aaa cag caa aat cag tac cag 1815
Pro Pro Val Asn Glu Pro Glu Thr Leu Lys Gln Gln Asn Gln Tyr Gln
530 535 540
gcc agt tat aac cag agc ttt tct agt cag cct cac caa gta gaa caa 1863
Ala Ser Tyr Asn Gln Ser Phe Ser Ser Gln Pro His Gln Val Glu Gln
545 550 555
aca gag ctt cag caa gaa cag ctt caa aca gtg gtt ggc act tac cat 1911
Thr Glu Leu Gln Gln Glu Gln Leu Gln Thr Val Val Gly Thr Tyr His
560 565 570
ggt tcc cca gac cag tcc cat caa gtg act ggt aac cac cag cag cct 1959
Gly Ser Pro Asp Gln Ser His Gln Val Thr Gly Asn His Gln Gln Pro
575 580 585 590
cct cag cag aac act gga ttt cca cgt agc aat cag ccc tat tac aat 2007
Pro Gln Gln Asn Thr Gly Phe Pro Arg Ser Asn Gln Pro Tyr Tyr Asn
595 600 605
agt cgt ggt gtg tct cgt gga ggc tcc cgt ggt gct aga ggc ttg atg 2055
Ser Arg Gly Val Ser Arg Gly Gly Ser Arg Gly Ala Arg Gly Leu Met
610 615 620
aat gga tac cgg ggc cct gcc aat gga ttc aga gga gga tat gat ggt 2103
Asn Gly Tyr Arg Gly Pro Ala Asn Gly Phe Arg Gly Gly Tyr Asp Gly
625 630 635
tac cgc cct tca ttc tct aac act cca aac agt ggt tat aca cag tct 2151
Tyr Arg Pro Ser Phe Ser Asn Thr Pro Asn Ser Gly Tyr Thr Gln Ser
640 645 650
cag ttc agt gct ccc cgg gat tac tct ggc tat caa cgg gat gga tat 2199
Gln Phe Ser Ala Pro Arg Asp Tyr Ser Gly Tyr Gln Arg Asp Gly Tyr
655 660 665 670
cag cag aat ttc aag cga ggc tct ggg cag agt gga cca cgg gga gcc 2247
Gln Gln Asn Phe Lys Arg Gly Ser Gly Gln Ser Gly Pro Arg Gly Ala
675 680 685
cca cga ggt aat att ttg tgg tgg tga tcctagctcc taagtggagc 2294
Pro Arg Gly Asn Ile Leu Trp Trp
690
ttctgttctg gccttggaag agctgttaat agtctgcatg ttaggaatac atttatcctt 2354
tccagacttg ttgctaggga ttaaatgaaa tgctctgttt ctaaaactta atcttggacc 2414
caaattttaa tttttgaatg atttaatttt ccctgttact atataaactg tcttgaaaac 2474
tagaacatat tctcttctca gaaaaagtgt ttttccaact gaaaattatt tttcaggtcc 2534
taaaacctgc taaatgtttt taggaagtac ttactgaaac atttttgtaa gacatttttg 2594
gaatgagatt gaacatttat ataaatttat tattcctctt tcattttttt gaaacatgcc 2654
tattatattt tagggccaga caccctttaa tggccggata agccatagtt aacatttaga 2714
gaaccattta gaagtgatag aactaatgga atttgcaatg ccttttggac ctctattagt 2774
gatataaata tcaagttatt tctgactttt aaacaaaact cccaaattcc taacttattg 2834
agctatactt aaaaaaaatt acaggtttag agagtttttt gtttttcttt tactgttgga 2894
aaactacttc ccattttggc aggaagttaa cctatttaac aattagagct agcatttcat 2954
gtagtctgaa attctaaatg gttctctgat ttgagggagg ttaaacatca aacaggtttc 3014
ctctattggc cataacatgt ataaaatgtg tgttaaggag gaattacaac gtactttgat 3074
ttgaatacta gtagaaactg gccaggaaaa aggtacattt ttctaaaaat taatggatca 3134
cttgggaatt actgacttga ctagaagtat caaaggatgt ttgcatgtga atgtgggtta 3194
tgttctttcc caccttgtag catattcgat gaaagttgag ttaactgata gctaaaaatc 3254
tgttttaaca gcatgtaaaa agttatttta tctgttaaaa gtcattatac agttttgaat 3314
gttatgtagt ttctttttaa cagtttaggt aataaggtct gttttcattc tggtgctttt 3374
attaattttg atagtatgat gttacttact actgaaatgt aagctagagt gtacactaga 3434
atgtaagctc catgagagca ggtaccttgt ctgtcttctc tgctgtatct attcccaacg 3494
cttgatgatg gtgcctggca catagtaggc actcaataaa tatttgttga atgaatgaa 3553
<210> 4
<211> 694
<212> PRT
<213> 人(Homo sapiens)
<400> 4
Met Pro Ser Ala Thr Ser His Ser Gly Ser Gly Ser Lys Ser Ser Gly
1 5 10 15
Pro Pro Pro Pro Ser Gly Ser Ser Gly Ser Glu Ala Ala Ala Gly Ala
20 25 30
Gly Ala Ala Ala Pro Ala Ser Gln His Pro Ala Thr Gly Thr Gly Ala
35 40 45
Val Gln Thr Glu Ala Met Lys Gln Ile Leu Gly Val Ile Asp Lys Lys
50 55 60
Leu Arg Asn Leu Glu Lys Lys Lys Gly Lys Leu Asp Asp Tyr Gln Glu
65 70 75 80
Arg Met Asn Lys Gly Glu Arg Leu Asn Gln Asp Gln Leu Asp Ala Val
85 90 95
Ser Lys Tyr Gln Glu Val Thr Asn Asn Leu Glu Phe Ala Lys Glu Leu
100 105 110
Gln Arg Ser Phe Met Ala Leu Ser Gln Asp Ile Gln Lys Thr Ile Lys
115 120 125
Lys Thr Ala Arg Arg Glu Gln Leu Met Arg Glu Glu Ala Glu Gln Lys
130 135 140
Arg Leu Lys Thr Val Leu Glu Leu Gln Tyr Val Leu Asp Lys Leu Gly
145 150 155 160
Asp Asp Glu Val Arg Thr Asp Leu Lys Gln Gly Leu Asn Gly Val Pro
165 170 175
Ile Leu Ser Glu Glu Glu Leu Ser Leu Leu Asp Glu Phe Tyr Lys Leu
180 185 190
Val Asp Pro Glu Arg Asp Met Ser Leu Arg Leu Asn Glu Gln Tyr Glu
195 200 205
His Ala Ser Ile His Leu Trp Asp Leu Leu Glu Gly Lys Glu Lys Pro
210 215 220
Val Cys Gly Thr Thr Tyr Lys Val Leu Lys Glu Ile Val Glu Arg Val
225 230 235 240
Phe Gln Ser Asn Tyr Phe Asp Ser Thr His Asn His Gln Asn Gly Leu
245 250 255
Cys Glu Glu Glu Glu Ala Ala Ser Ala Pro Ala Val Glu Asp Gln Val
260 265 270
Pro Glu Ala Glu Pro Glu Pro Ala Glu Glu Tyr Thr Glu Gln Ser Glu
275 280 285
Val Glu Ser Thr Glu Tyr Val Asn Arg Gln Phe Met Ala Glu Thr Gln
290 295 300
Phe Thr Ser Gly Glu Lys Glu Gln Val Asp Glu Trp Thr Val Glu Thr
305 310 315 320
Val Glu Val Val Asn Ser Leu Gln Gln Gln Pro Gln Ala Ala Ser Pro
325 330 335
Ser Val Pro Glu Pro His Ser Leu Thr Pro Val Ala Gln Ala Asp Pro
340 345 350
Leu Val Arg Arg Gln Arg Val Gln Asp Leu Met Ala Gln Met Gln Gly
355 360 365
Pro Tyr Asn Phe Ile Gln Asp Ser Met Leu Asp Phe Glu Asn Gln Thr
370 375 380
Leu Asp Pro Ala Ile Val Ser Ala Gln Pro Met Asn Pro Thr Gln Asn
385 390 395 400
Met Asp Met Pro Gln Leu Val Cys Pro Pro Val His Ser Glu Ser Arg
405 410 415
Leu Ala Gln Pro Asn Gln Val Pro Val Gln Pro Glu Ala Thr Gln Val
420 425 430
Pro Leu Val Ser Ser Thr Ser Glu Gly Tyr Thr Ala Ser Gln Pro Leu
435 440 445
Tyr Gln Pro Ser His Ala Thr Glu Gln Arg Pro Gln Lys Glu Pro Ile
450 455 460
Asp Gln Ile Gln Ala Thr Ile Ser Leu Asn Thr Asp Gln Thr Thr Ala
465 470 475 480
Ser Ser Ser Leu Pro Ala Ala Ser Gln Pro Gln Val Phe Gln Ala Gly
485 490 495
Thr Ser Lys Pro Leu His Ser Ser Gly Ile Asn Val Asn Ala Ala Pro
500 505 510
Phe Gln Ser Met Gln Thr Val Phe Asn Met Asn Ala Pro Val Pro Pro
515 520 525
Val Asn Glu Pro Glu Thr Leu Lys Gln Gln Asn Gln Tyr Gln Ala Ser
530 535 540
Tyr Asn Gln Ser Phe Ser Ser Gln Pro His Gln Val Glu Gln Thr Glu
545 550 555 560
Leu Gln Gln Glu Gln Leu Gln Thr Val Val Gly Thr Tyr His Gly Ser
565 570 575
Pro Asp Gln Ser His Gln Val Thr Gly Asn His Gln Gln Pro Pro Gln
580 585 590
Gln Asn Thr Gly Phe Pro Arg Ser Asn Gln Pro Tyr Tyr Asn Ser Arg
595 600 605
Gly Val Ser Arg Gly Gly Ser Arg Gly Ala Arg Gly Leu Met Asn Gly
610 615 620
Tyr Arg Gly Pro Ala Asn Gly Phe Arg Gly Gly Tyr Asp Gly Tyr Arg
625 630 635 640
Pro Ser Phe Ser Asn Thr Pro Asn Ser Gly Tyr Thr Gln Ser Gln Phe
645 650 655
Ser Ala Pro Arg Asp Tyr Ser Gly Tyr Gln Arg Asp Gly Tyr Gln Gln
660 665 670
Asn Phe Lys Arg Gly Ser Gly Gln Ser Gly Pro Arg Gly Ala Pro Arg
675 680 685
Gly Asn Ile Leu Trp Trp
690
<210> 5
<211> 1605
<212> DNA
<213> 犬(Canis familiaris)
<220>
<221> CDS
<222> (46)..(1392)
<400> 5
gtcacaaata acttggagtt tgcaaaagaa ttacagagga gtttc atg gca tta agt 57
Met Ala Leu Ser
1
caa gat att cag aaa aca ata aag aag act gca cgt cgg gag cag ctt 105
Gln Asp Ile Gln Lys Thr Ile Lys Lys Thr Ala Arg Arg Glu Gln Leu
5 10 15 20
atg aga gag gaa gcg gaa caa aaa cgt tta aaa act gta ctt gag ctc 153
Met Arg Glu Glu Ala Glu Gln Lys Arg Leu Lys Thr Val Leu Glu Leu
25 30 35
cag tat gtt ttg gac aaa ttg gga gat gat gaa gtg aga act gac ctg 201
Gln Tyr Val Leu Asp Lys Leu Gly Asp Asp Glu Val Arg Thr Asp Leu
40 45 50
aag caa ggt ttg aat gga gtg cca ata ttg tct gaa gaa gaa ttg tcg 249
Lys Gln Gly Leu Asn Gly Val Pro Ile Leu Ser Glu Glu Glu Leu Ser
55 60 65
ttg ttg gat gaa ttc tac aaa tta gca gac cct gaa cgg gac atg agc 297
Leu Leu Asp Glu Phe Tyr Lys Leu Ala Asp Pro Glu Arg Asp Met Ser
70 75 80
ttg agg ttg aat gag cag tat gaa cat gct tcc att cac ctg tgg gac 345
Leu Arg Leu Asn Glu Gln Tyr Glu His Ala Ser Ile His Leu Trp Asp
85 90 95 100
ttg ctg gaa gga aag gaa aag tct gta tgt gga aca acc tat aaa gca 393
Leu Leu Glu Gly Lys Glu Lys Ser Val Cys Gly Thr Thr Tyr Lys Ala
105 110 115
cta aag gaa att gtt gag cgt gtt ttc cag tca aat tac ttt gac agc 441
Leu Lys Glu Ile Val Glu Arg Val Phe Gln Ser Asn Tyr Phe Asp Ser
120 125 130
act cac aac cac cag aat ggg cta tgt gag gaa gaa gag gca gcc tca 489
Thr His Asn His Gln Asn Gly Leu Cys Glu Glu Glu Glu Ala Ala Ser
135 140 145
gca cct aca gtt gaa gac cag gta gct gaa gct gag cct gag cca gca 537
Ala Pro Thr Val Glu Asp Gln Val Ala Glu Ala Glu Pro Glu Pro Ala
150 155 160
gaa gaa tac act gaa caa agt gaa gtt gaa tca aca gag tat gta aat 585
Glu Glu Tyr Thr Glu Gln Ser Glu Val Glu Ser Thr Glu Tyr Val Asn
165 170 175 180
aga caa ttt atg gca gaa aca cag ttc agc agt ggt gaa aag gag cag 633
Arg Gln Phe Met Ala Glu Thr Gln Phe Ser Ser Gly Glu Lys Glu Gln
185 190 195
gta gat gag tgg acg gtc gaa aca gtg gag gtg gtg aat tca ctc cag 681
Val Asp Glu Trp Thr Val Glu Thr Val Glu Val Val Asn Ser Leu Gln
200 205 210
cag caa cct cag gct gcg tct cct tca gta cca gag ccc cac tct ttg 729
Gln Gln Pro Gln Ala Ala Ser Pro Ser Val Pro Glu Pro His Ser Leu
215 220 225
act ccg gtg gct cag gca gat ccc ctt gtg aga aga cag cga gtc cag 777
Thr Pro Val Ala Gln Ala Asp Pro Leu Val Arg Arg Gln Arg Val Gln
230 235 240
gac ctt atg gcg cag atg cag ggg ccc tat aat ttc ata cag gat tca 825
Asp Leu Met Ala Gln Met Gln Gly Pro Tyr Asn Phe Ile Gln Asp Ser
245 250 255 260
atg ctg gat ttt gaa aac cag aca ctc gat cct gcc att gta tct gca 873
Met Leu Asp Phe Glu Asn Gln Thr Leu Asp Pro Ala Ile Val Ser Ala
265 270 275
cag cct atg aat ccg aca caa aac atg gac atg ccc cag ctg gtt tgc 921
Gln Pro Met Asn Pro Thr Gln Asn Met Asp Met Pro Gln Leu Val Cys
280 285 290
cct cca gtt cat tct gaa tct aga ctt gct caa cct aat caa gtt cct 969
Pro Pro Val His Ser Glu Ser Arg Leu Ala Gln Pro Asn Gln Val Pro
295 300 305
gta caa cca gaa gct aca cag gtt cct ttg gtt tca tcc aca agt gag 1017
Val Gln Pro Glu Ala Thr Gln Val Pro Leu Val Ser Ser Thr Ser Glu
310 315 320
ggg tat aca gca tct caa ccc ttg tac cag cct tct cat gct aca gag 1065
Gly Tyr Thr Ala Ser Gln Pro Leu Tyr Gln Pro Ser His Ala Thr Glu
325 330 335 340
caa cga cca caa aag gaa cca att gac cag att cag gca aca atc tct 1113
Gln Arg Pro Gln Lys Glu Pro Ile Asp Gln Ile Gln Ala Thr Ile Ser
345 350 355
tta aat aca gac cag act aca gcg tca tca tcc ctt ccg gct gct tct 1161
Leu Asn Thr Asp Gln Thr Thr Ala Ser Ser Ser Leu Pro Ala Ala Ser
360 365 370
cag cct cag gta ttc cag gct ggg aca agc aaa cca tta cat agc agt 1209
Gln Pro Gln Val Phe Gln Ala Gly Thr Ser Lys Pro Leu His Ser Ser
375 380 385
gga atc aat gta aat gca gct cca ttc caa tcc atg caa acg gtg ttc 1257
Gly Ile Asn Val Asn Ala Ala Pro Phe Gln Ser Met Gln Thr Val Phe
390 395 400
aat atg aat gcc cca gtt cct cct gtt aat gaa cca gaa act ttg aaa 1305
Asn Met Asn Ala Pro Val Pro Pro Val Asn Glu Pro Glu Thr Leu Lys
405 410 415 420
caa caa aat cag tac cag gcc agt tat aac cag agc ttt tct agt cag 1353
Gln Gln Asn Gln Tyr Gln Ala Ser Tyr Asn Gln Ser Phe Ser Ser Gln
425 430 435
cct cac caa gta gaa caa aca gag gga tgc cgc aaa tga acactcagca 1402
Pro His Gln Val Glu Gln Thr Glu Gly Cys Arg Lys
440 445
agtgaattaa tctgattcac aggattatgt ttaaacgcca aaaacacact ggccagtgta 1462
ccataatatg ttaccagaag agttattatc tatttgttct ccctttcagg aaacttattg 1522
taaagggact gttttcatcc cataaagaca ggactacaat tgtcagcttt atattacctg 1582
gaaaaaaaaa aaaaaaaaaa aaa 1605
<210> 6
<211> 448
<212> PRT
<213> 犬(Canis familiaris)
<400> 6
Met Ala Leu Ser Gln Asp Ile Gln Lys Thr Ile Lys Lys Thr Ala Arg
1 5 10 15
Arg Glu Gln Leu Met Arg Glu Glu Ala Glu Gln Lys Arg Leu Lys Thr
20 25 30
Val Leu Glu Leu Gln Tyr Val Leu Asp Lys Leu Gly Asp Asp Glu Val
35 40 45
Arg Thr Asp Leu Lys Gln Gly Leu Asn Gly Val Pro Ile Leu Ser Glu
50 55 60
Glu Glu Leu Ser Leu Leu Asp Glu Phe Tyr Lys Leu Ala Asp Pro Glu
65 70 75 80
Arg Asp Met Ser Leu Arg Leu Asn Glu Gln Tyr Glu His Ala Ser Ile
85 90 95
His Leu Trp Asp Leu Leu Glu Gly Lys Glu Lys Ser Val Cys Gly Thr
100 105 110
Thr Tyr Lys Ala Leu Lys Glu Ile Val Glu Arg Val Phe Gln Ser Asn
115 120 125
Tyr Phe Asp Ser Thr His Asn His Gln Asn Gly Leu Cys Glu Glu Glu
130 135 140
Glu Ala Ala Ser Ala Pro Thr Val Glu Asp Gln Val Ala Glu Ala Glu
145 150 155 160
Pro Glu Pro Ala Glu Glu Tyr Thr Glu Gln Ser Glu Val Glu Ser Thr
165 170 175
Glu Tyr Val Asn Arg Gln Phe Met Ala Glu Thr Gln Phe Ser Ser Gly
180 185 190
Glu Lys Glu Gln Val Asp Glu Trp Thr Val Glu Thr Val Glu Val Val
195 200 205
Asn Ser Leu Gln Gln Gln Pro Gln Ala Ala Ser Pro Ser Val Pro Glu
210 215 220
Pro His Ser Leu Thr Pro Val Ala Gln Ala Asp Pro Leu Val Arg Arg
225 230 235 240
Gln Arg Val Gln Asp Leu Met Ala Gln Met Gln Gly Pro Tyr Asn Phe
245 250 255
Ile Gln Asp Ser Met Leu Asp Phe Glu Asn Gln Thr Leu Asp Pro Ala
260 265 270
Ile Val Ser Ala Gln Pro Met Asn Pro Thr Gln Asn Met Asp Met Pro
275 280 285
Gln Leu Val Cys Pro Pro Val His Ser Glu Ser Arg Leu Ala Gln Pro
290 295 300
Asn Gln Val Pro Val Gln Pro Glu Ala Thr Gln Val Pro Leu Val Ser
305 310 315 320
Ser Thr Ser Glu Gly Tyr Thr Ala Ser Gln Pro Leu Tyr Gln Pro Ser
325 330 335
His Ala Thr Glu Gln Arg Pro Gln Lys Glu Pro Ile Asp Gln Ile Gln
340 345 350
Ala Thr Ile Ser Leu Asn Thr Asp Gln Thr Thr Ala Ser Ser Ser Leu
355 360 365
Pro Ala Ala Ser Gln Pro Gln Val Phe Gln Ala Gly Thr Ser Lys Pro
370 375 380
Leu His Ser Ser Gly Ile Asn Val Asn Ala Ala Pro Phe Gln Ser Met
385 390 395 400
Gln Thr Val Phe Asn Met Asn Ala Pro Val Pro Pro Val Asn Glu Pro
405 410 415
Glu Thr Leu Lys Gln Gln Asn Gln Tyr Gln Ala Ser Tyr Asn Gln Ser
420 425 430
Phe Ser Ser Gln Pro His Gln Val Glu Gln Thr Glu Gly Cys Arg Lys
435 440 445
<210> 7
<211> 4154
<212> DNA
<213> 犬(Canis familiaris)
<220>
<221> CDS
<222> (1)..(2154)
<400> 7
atg ccg tcg gcc acc agc ctc agc gga agc ggc agc aag tcg tcg ggc 48
Met Pro Ser Ala Thr Ser Leu Ser Gly Ser Gly Ser Lys Ser Ser Gly
1 5 10 15
ccg ccg ccc ccg tcg ggt tcc tcc ggg agc gag gcg gcg gcg gcg gcg 96
Pro Pro Pro Pro Ser Gly Ser Ser Gly Ser Glu Ala Ala Ala Ala Ala
20 25 30
ggg gcg gcg ggg gcg gcg ggg gcc ggg gcg gct gcg ccc gcc tcc cag 144
Gly Ala Ala Gly Ala Ala Gly Ala Gly Ala Ala Ala Pro Ala Ser Gln
35 40 45
cac ccc gcg acc ggc acc ggc gct gtc cag acc gag gcc atg aag cag 192
His Pro Ala Thr Gly Thr Gly Ala Val Gln Thr Glu Ala Met Lys Gln
50 55 60
atc ctc ggg gtg atc gac aag aaa ctc cgg aac ctg gag aag aaa aag 240
Ile Leu Gly Val Ile Asp Lys Lys Leu Arg Asn Leu Glu Lys Lys Lys
65 70 75 80
ggc aag ctt gat gat tac cag gaa cga atg aac aaa ggg gaa agg ctt 288
Gly Lys Leu Asp Asp Tyr Gln Glu Arg Met Asn Lys Gly Glu Arg Leu
85 90 95
aat caa gat cag ctg gat gcc gta tct aag tac cag gaa gtc aca aat 336
Asn Gln Asp Gln Leu Asp Ala Val Ser Lys Tyr Gln Glu Val Thr Asn
100 105 110
aac ttg gag ttt gca aaa gaa tta cag agg agt ttc atg gca tta agt 384
Asn Leu Glu Phe Ala Lys Glu Leu Gln Arg Ser Phe Met Ala Leu Ser
115 120 125
caa gat att cag aaa aca ata aag aag act gca cgt cgg gag cag ctt 432
Gln Asp Ile Gln Lys Thr Ile Lys Lys Thr Ala Arg Arg Glu Gln Leu
130 135 140
atg aga gag gaa gcg gaa caa aaa cgt tta aaa act gta ctt gag ctc 480
Met Arg Glu Glu Ala Glu Gln Lys Arg Leu Lys Thr Val Leu Glu Leu
145 150 155 160
cag tat gtt ttg gac aaa ttg gga gat gat gaa gtg aga act gac ctg 528
Gln Tyr Val Leu Asp Lys Leu Gly Asp Asp Glu Val Arg Thr Asp Leu
165 170 175
aag caa ggt ttg aat gga gtg cca ata ttg tct gaa gaa gaa ttg tcg 576
Lys Gln Gly Leu Asn Gly Val Pro Ile Leu Ser Glu Glu Glu Leu Ser
180 185 190
ttg ttg gat gaa ttc tac aaa tta gca gac cct gaa cgg gac atg agc 624
Leu Leu Asp Glu Phe Tyr Lys Leu Ala Asp Pro Glu Arg Asp Met Ser
195 200 205
ttg agg ttg aat gag cag tat gaa cat gct tcc att cac ctg tgg gac 672
Leu Arg Leu Asn Glu Gln Tyr Glu His Ala Ser Ile His Leu Trp Asp
210 215 220
ttg ctg gaa gga aag gaa aag tct gta tgt gga aca acc tat aaa gca 720
Leu Leu Glu Gly Lys Glu Lys Ser Val Cys Gly Thr Thr Tyr Lys Ala
225 230 235 240
cta aag gaa att gtt gag cgt gtt ttc cag tca aat tac ttt gac agc 768
Leu Lys Glu Ile Val Glu Arg Val Phe Gln Ser Asn Tyr Phe Asp Ser
245 250 255
act cac aac cac cag aat ggg cta tgt gag gaa gaa gag gca gcc tca 816
Thr His Asn His Gln Asn Gly Leu Cys Glu Glu Glu Glu Ala Ala Ser
260 265 270
gca cct aca gtt gaa gac cag gta gct gaa gct gag cct gag cca gca 864
Ala Pro Thr Val Glu Asp Gln Val Ala Glu Ala Glu Pro Glu Pro Ala
275 280 285
gaa gaa tac act gaa caa agt gaa gtt gaa tca aca gag tat gta aat 912
Glu Glu Tyr Thr Glu Gln Ser Glu Val Glu Ser Thr Glu Tyr Val Asn
290 295 300
aga caa ttt atg gca gaa aca cag ttc agc agt ggt gaa aag gag cag 960
Arg Gln Phe Met Ala Glu Thr Gln Phe Ser Ser Gly Glu Lys Glu Gln
305 310 315 320
gta gat gag tgg acg gtc gaa aca gtg gag gtg gtg aat tca ctc cag 1008
Val Asp Glu Trp Thr Val Glu Thr Val Glu Val Val Asn Ser Leu Gln
325 330 335
cag caa cct cag gct gcg tct cct tca gta cca gag ccc cac tct ttg 1056
Gln Gln Pro Gln Ala Ala Ser Pro Ser Val Pro Glu Pro His Ser Leu
340 345 350
act ccg gtg gct cag gca gat ccc ctt gtg aga aga cag cga gtc cag 1104
Thr Pro Val Ala Gln Ala Asp Pro Leu Val Arg Arg Gln Arg Val Gln
355 360 365
gac ctt atg gcg cag atg cag ggg ccc tat aat ttc ata cag gat tca 1152
Asp Leu Met Ala Gln Met Gln Gly Pro Tyr Asn Phe Ile Gln Asp Ser
370 375 380
atg ctg gat ttt gaa aac cag aca ctc gat cct gcc att gta tct gca 1200
Met Leu Asp Phe Glu Asn Gln Thr Leu Asp Pro Ala Ile Val Ser Ala
385 390 395 400
cag cct atg aat ccg aca caa aac atg gac atg ccc cag ctg gtt tgc 1248
Gln Pro Met Asn Pro Thr Gln Asn Met Asp Met Pro Gln Leu Val Cys
405 410 415
cct cca gtt cat tct gaa tct aga ctt gct caa cct aat caa gtt cct 1296
Pro Pro Val His Ser Glu Ser Arg Leu Ala Gln Pro Asn Gln Val Pro
420 425 430
gta caa cca gaa gct aca cag gtt cct ttg gtt tca tcc aca agt gag 1344
Val Gln Pro Glu Ala Thr Gln Val Pro Leu Val Ser Ser Thr Ser Glu
435 440 445
ggg tat aca gca tct caa ccc ttg tac cag cct tct cat gct aca gag 1392
Gly Tyr Thr Ala Ser Gln Pro Leu Tyr Gln Pro Ser His Ala Thr Glu
450 455 460
caa cga cca caa aag gaa cca att gac cag att cag gca aca atc tct 1440
Gln Arg Pro Gln Lys Glu Pro Ile Asp Gln Ile Gln Ala Thr Ile Ser
465 470 475 480
tta aat aca gac cag act aca gcg tca tca tcc ctt ccg gct gct tct 1488
Leu Asn Thr Asp Gln Thr Thr Ala Ser Ser Ser Leu Pro Ala Ala Ser
485 490 495
cag cct cag gta ttc cag gct ggg aca agc aaa cca tta cat agc agt 1536
Gln Pro Gln Val Phe Gln Ala Gly Thr Ser Lys Pro Leu His Ser Ser
500 505 510
gga atc aat gta aat gca gct cca ttc caa tcc atg caa acg gtg ttc 1584
Gly Ile Asn Val Asn Ala Ala Pro Phe Gln Ser Met Gln Thr Val Phe
515 520 525
aat atg aat gcc cca gtt cct cct gtt aat gaa cca gaa act ttg aaa 1632
Asn Met Asn Ala Pro Val Pro Pro Val Asn Glu Pro Glu Thr Leu Lys
530 535 540
caa caa aat cag tac cag gcc agt tat aac cag agc ttt tct agt cag 1680
Gln Gln Asn Gln Tyr Gln Ala Ser Tyr Asn Gln Ser Phe Ser Ser Gln
545 550 555 560
cct cac caa gta gaa caa aca gac ctt cag caa gaa cag ctt caa aca 1728
Pro His Gln Val Glu Gln Thr Asp Leu Gln Gln Glu Gln Leu Gln Thr
565 570 575
gtg gtt ggc act tac cat ggt tcc cag gac cag ccc cac caa gtg act 1776
Val Val Gly Thr Tyr His Gly Ser Gln Asp Gln Pro His Gln Val Thr
580 585 590
ggt aac cat cag cag cct ccc cag cag aac act gga ttt cca cgt agc 1824
Gly Asn His Gln Gln Pro Pro Gln Gln Asn Thr Gly Phe Pro Arg Ser
595 600 605
agt cag ccc tat tac aat agt cgt ggt gtg tct cgt ggt ggt tcc cgt 1872
Ser Gln Pro Tyr Tyr Asn Ser Arg Gly Val Ser Arg Gly Gly Ser Arg
610 615 620
ggt gct aga ggc tta atg aat gga tac agg ggc cct gcc aat gga ttc 1920
Gly Ala Arg Gly Leu Met Asn Gly Tyr Arg Gly Pro Ala Asn Gly Phe
625 630 635 640
aga gga gga tat gat ggt tac cgc cct tca ttc tct aac act cca aac 1968
Arg Gly Gly Tyr Asp Gly Tyr Arg Pro Ser Phe Ser Asn Thr Pro Asn
645 650 655
agt ggt tat aca cag tct cag ttc agt gct ccc cgg gac tac tct ggc 2016
Ser Gly Tyr Thr Gln Ser Gln Phe Ser Ala Pro Arg Asp Tyr Ser Gly
660 665 670
tat cag cgg gat gga tat cag cag aat ttc aag cga ggc tct ggg cag 2064
Tyr Gln Arg Asp Gly Tyr Gln Gln Asn Phe Lys Arg Gly Ser Gly Gln
675 680 685
agt gga cca cgg gga gcc cca cga ggt cgt gga ggg ccc cca aga ccc 2112
Ser Gly Pro Arg Gly Ala Pro Arg Gly Arg Gly Gly Pro Pro Arg Pro
690 695 700
aac aga ggg atg ccg caa atg aac act cag caa gtg aat taa 2154
Asn Arg Gly Met Pro Gln Met Asn Thr Gln Gln Val Asn
705 710 715
tctgattcac aggattatgt ttaaacgcca aaaacacact ggccagtgta ccataatatg 2214
ttaccagaag agttattatc tatttgttct ccctttcagg aaacttattg taaagggact 2274
gttttcatcc cataaagaca ggactacaat tgtcagcttt atattacctg gatatggaag 2334
gaaactattt ttattctgca tgttcttcct aagcgtcatc ttgagccttg cacatgatac 2394
tcagattcct cacccttgct taggagtaaa acataataca ctttacaggg tgatatctcc 2454
atagttattt gaagtggctt ggaaaaagca agattaactt ctgacattgg ataaaaatca 2514
acaaatcagc cctagagtta ttcaaatggt aattgacaaa aactaaaata tttcccttcg 2574
agaaggagtg gaatgtggtt tggcagaaca actgcatttc acagcttttc cggttaaatt 2634
ggagcactaa acgtttagat gcataccaaa ttatgcatgg gcccttaata taaaaggctg 2694
gctaccagct ttgacacagc actattcatc ctctggccaa acaactgtgg ttaaacaaca 2754
catgtaaatt gctttttaac agctgatact ataataagac aaagccaaaa tgcaaaaatt 2814
gggctttgat tggcactttt tgaaaaatat gcaacaaata tgggatgtaa tctggatggc 2874
cgcttctgta cttaatgtga agtatttaga tacctttttg aacacttaac agtttcttct 2934
gacaatgact tttgtaagga ttggtactat ctatcattcc ttataatgta cattgtctgt 2994
cactaatcct cagatcttgc tgtattgtca cctaaattgg tacaggtact gatgaaaata 3054
tctaatggat aatcataaca ctcttggtca catgtttttc ctgcagcctg aaggttttta 3114
aaagaaaaag atatcaaatg cctgctgcta ccaccctttt aaattgctat cttttgaaaa 3174
gcaccagtat gtgttttaga ttgatttccc tattttaggg aaatgacaga cagtagtttc 3234
agttctgatg gtataagcaa aacaaataaa acatgtttat aaaagttgta tcttgaaaca 3294
ctggtgttca acagctagca gcttatgtgg ttcaccccat gcattgttag tgtttcagat 3354
tttatggtta tctccagcag ctgtttctgt agtacttgca tttatctttt gtctaaccct 3414
aatattctca cggaggcatt tatattcaaa gtggtgatcc cttcacttag acgcataggg 3474
agagtcacaa gtttgatgaa gaggacagtg tagtaattta tatgctgttg gaatttgtgc 3534
tagcagtttg agcactagtt ctgtgtgcct atgaacttaa tgctgcttgt catattccac 3594
tttgacttca tggagaatta atcccatcta ctcagcaaag gctatactaa tactaagtta 3654
atggtatttt ctgtgcagaa attgaatttt gttttattag catttagcta aggaattttt 3714
ccagtaggtg ctcagctact aaagaaaaac aaaaacaaga cacaaaacta ttctcaaaca 3774
ttcattgtta gacaactgga gtttttgctg gttttgtaac ctactaaaat ggataggctg 3834
ttgaacattc cacattcaaa agttttttgt agggtggtgg ggaagggggg gtgtcttcaa 3894
tgtttatttt aaaataaaat aagttcttga cttttctcat gtgtggttgt ggtacatcat 3954
attggaaggg ttatctgttt acttttgcaa atgagtattt ctcttgctag cacctcccgt 4014
tgtgcgcttt aaatgacatc tgcctgggat gtaccacaac catatgttag ctgtatttta 4074
tggggaatag ataaaatatt cgtggtttat tgggtaatcc ctagatgtgt atgcttacaa 4134
tcctatatat aaaactaaat 4154
<210> 8
<211> 717
<212> PRT
<213> 犬(Canis familiaris)
<400> 8
Met Pro Ser Ala Thr Ser Leu Ser Gly Ser Gly Ser Lys Ser Ser Gly
1 5 10 15
Pro Pro Pro Pro Ser Gly Ser Ser Gly Ser Glu Ala Ala Ala Ala Ala
20 25 30
Gly Ala Ala Gly Ala Ala Gly Ala Gly Ala Ala Ala Pro Ala Ser Gln
35 40 45
His Pro Ala Thr Gly Thr Gly Ala Val Gln Thr Glu Ala Met Lys Gln
50 55 60
Ile Leu Gly Val Ile Asp Lys Lys Leu Arg Asn Leu Glu Lys Lys Lys
65 70 75 80
Gly Lys Leu Asp Asp Tyr Gln Glu Arg Met Asn Lys Gly Glu Arg Leu
85 90 95
Asn Gln Asp Gln Leu Asp Ala Val Ser Lys Tyr Gln Glu Val Thr Asn
100 105 110
Asn Leu Glu Phe Ala Lys Glu Leu Gln Arg Ser Phe Met Ala Leu Ser
115 120 125
Gln Asp Ile Gln Lys Thr Ile Lys Lys Thr Ala Arg Arg Glu Gln Leu
130 135 140
Met Arg Glu Glu Ala Glu Gln Lys Arg Leu Lys Thr Val Leu Glu Leu
145 150 155 160
Gln Tyr Val Leu Asp Lys Leu Gly Asp Asp Glu Val Arg Thr Asp Leu
165 170 175
Lys Gln Gly Leu Asn Gly Val Pro Ile Leu Ser Glu Glu Glu Leu Ser
180 185 190
Leu Leu Asp Glu Phe Tyr Lys Leu Ala Asp Pro Glu Arg Asp Met Ser
195 200 205
Leu Arg Leu Asn Glu Gln Tyr Glu His Ala Ser Ile His Leu Trp Asp
210 215 220
Leu Leu Glu Gly Lys Glu Lys Ser Val Cys Gly Thr Thr Tyr Lys Ala
225 230 235 240
Leu Lys Glu Ile Val Glu Arg Val Phe Gln Ser Asn Tyr Phe Asp Ser
245 250 255
Thr His Asn His Gln Asn Gly Leu Cys Glu Glu Glu Glu Ala Ala Ser
260 265 270
Ala Pro Thr Val Glu Asp Gln Val Ala Glu Ala Glu Pro Glu Pro Ala
275 280 285
Glu Glu Tyr Thr Glu Gln Ser Glu Val Glu Ser Thr Glu Tyr Val Asn
290 295 300
Arg Gln Phe Met Ala Glu Thr Gln Phe Ser Ser Gly Glu Lys Glu Gln
305 310 315 320
Val Asp Glu Trp Thr Val Glu Thr Val Glu Val Val Asn Ser Leu Gln
325 330 335
Gln Gln Pro Gln Ala Ala Ser Pro Ser Val Pro Glu Pro His Ser Leu
340 345 350
Thr Pro Val Ala Gln Ala Asp Pro Leu Val Arg Arg Gln Arg Val Gln
355 360 365
Asp Leu Met Ala Gln Met Gln Gly Pro Tyr Asn Phe Ile Gln Asp Ser
370 375 380
Met Leu Asp Phe Glu Asn Gln Thr Leu Asp Pro Ala Ile Val Ser Ala
385 390 395 400
Gln Pro Met Asn Pro Thr Gln Asn Met Asp Met Pro Gln Leu Val Cys
405 410 415
Pro Pro Val His Ser Glu Ser Arg Leu Ala Gln Pro Asn Gln Val Pro
420 425 430
Val Gln Pro Glu Ala Thr Gln Val Pro Leu Val Ser Ser Thr Ser Glu
435 440 445
Gly Tyr Thr Ala Ser Gln Pro Leu Tyr Gln Pro Ser His Ala Thr Glu
450 455 460
Gln Arg Pro Gln Lys Glu Pro Ile Asp Gln Ile Gln Ala Thr Ile Ser
465 470 475 480
Leu Asn Thr Asp Gln Thr Thr Ala Ser Ser Ser Leu Pro Ala Ala Ser
485 490 495
Gln Pro Gln Val Phe Gln Ala Gly Thr Ser Lys Pro Leu His Ser Ser
500 505 510
Gly Ile Asn Val Asn Ala Ala Pro Phe Gln Ser Met Gln Thr Val Phe
515 520 525
Asn Met Asn Ala Pro Val Pro Pro Val Asn Glu Pro Glu Thr Leu Lys
530 535 540
Gln Gln Asn Gln Tyr Gln Ala Ser Tyr Asn Gln Ser Phe Ser Ser Gln
545 550 555 560
Pro His Gln Val Glu Gln Thr Asp Leu Gln Gln Glu Gln Leu Gln Thr
565 570 575
Val Val Gly Thr Tyr His Gly Ser Gln Asp Gln Pro His Gln Val Thr
580 585 590
Gly Asn His Gln Gln Pro Pro Gln Gln Asn Thr Gly Phe Pro Arg Ser
595 600 605
Ser Gln Pro Tyr Tyr Asn Ser Arg Gly Val Ser Arg Gly Gly Ser Arg
610 615 620
Gly Ala Arg Gly Leu Met Asn Gly Tyr Arg Gly Pro Ala Asn Gly Phe
625 630 635 640
Arg Gly Gly Tyr Asp Gly Tyr Arg Pro Ser Phe Ser Asn Thr Pro Asn
645 650 655
Ser Gly Tyr Thr Gln Ser Gln Phe Ser Ala Pro Arg Asp Tyr Ser Gly
660 665 670
Tyr Gln Arg Asp Gly Tyr Gln Gln Asn Phe Lys Arg Gly Ser Gly Gln
675 680 685
Ser Gly Pro Arg Gly Ala Pro Arg Gly Arg Gly Gly Pro Pro Arg Pro
690 695 700
Asn Arg Gly Met Pro Gln Met Asn Thr Gln Gln Val Asn
705 710 715
<210> 9
<211> 4939
<212> DNA
<213> 犬(Canis familiaris)
<220>
<221> CDS
<222> (1)..(2109)
<400> 9
atg ccg tcg gcc acc agc ctc agc gga agc ggc agc aag tcg tcg ggc 48
Met Pro Ser Ala Thr Ser Leu Ser Gly Ser Gly Ser Lys Ser Ser Gly
1 5 10 15
ccg ccg ccc ccg tcg ggt tcc tcc ggg agc gag gcg gcg gcg gcg gcg 96
Pro Pro Pro Pro Ser Gly Ser Ser Gly Ser Glu Ala Ala Ala Ala Ala
20 25 30
ggg gcg gcg ggg gcg gcg ggg gcc ggg gcg gct gcg ccc gcc tcc cag 144
Gly Ala Ala Gly Ala Ala Gly Ala Gly Ala Ala Ala Pro Ala Ser Gln
35 40 45
cac ccc gcg acc ggc acc ggc gct gtc cag acc gag gcc atg aag cag 192
His Pro Ala Thr Gly Thr Gly Ala Val Gln Thr Glu Ala Met Lys Gln
50 55 60
atc ctc ggg gtg atc gac aag aaa ctc cgg aac ctg gag aag aaa aag 240
Ile Leu Gly Val Ile Asp Lys Lys Leu Arg Asn Leu Glu Lys Lys Lys
65 70 75 80
ggc aag ctt gat gat tac cag gaa cga atg aac aaa ggg gaa agg ctt 288
Gly Lys Leu Asp Asp Tyr Gln Glu Arg Met Asn Lys Gly Glu Arg Leu
85 90 95
aat caa gat cag ctg gat gcc gta tct aag tac cag gaa gtc aca aat 336
Asn Gln Asp Gln Leu Asp Ala Val Ser Lys Tyr Gln Glu Val Thr Asn
100 105 110
aac ttg gag ttt gca aaa gaa tta cag agg agt ttc atg gca tta agt 384
Asn Leu Glu Phe Ala Lys Glu Leu Gln Arg Ser Phe Met Ala Leu Ser
115 120 125
caa gat att cag aaa aca ata aag aag act gca cgt cgg gag cag ctt 432
Gln Asp Ile Gln Lys Thr Ile Lys Lys Thr Ala Arg Arg Glu Gln Leu
130 135 140
atg aga gag gaa gcg gaa caa aaa cgt tta aaa act gta ctt gag ctc 480
Met Arg Glu Glu Ala Glu Gln Lys Arg Leu Lys Thr Val Leu Glu Leu
145 150 155 160
cag tat gtt ttg gac aaa ttg gga gat gat gaa gtg aga act gac ctg 528
Gln Tyr Val Leu Asp Lys Leu Gly Asp Asp Glu Val Arg Thr Asp Leu
165 170 175
aag caa ggt ttg aat gga gtg cca ata ttg tct gaa gaa gaa ttg tcg 576
Lys Gln Gly Leu Asn Gly Val Pro Ile Leu Ser Glu Glu Glu Leu Ser
180 185 190
ttg ttg gat gaa ttc tac aaa tta gca gac cct gaa cgg gac atg agc 624
Leu Leu Asp Glu Phe Tyr Lys Leu Ala Asp Pro Glu Arg Asp Met Ser
195 200 205
ttg agg ttg aat gag cag tat gaa cat gct tcc att cac ctg tgg gac 672
Leu Arg Leu Asn Glu Gln Tyr Glu His Ala Ser Ile His Leu Trp Asp
210 215 220
ttg ctg gaa gga aag gaa aag tct gta tgt gga aca acc tat aaa gca 720
Leu Leu Glu Gly Lys Glu Lys Ser Val Cys Gly Thr Thr Tyr Lys Ala
225 230 235 240
cta aag gaa att gtt gag cgt gtt ttc cag tca aat tac ttt gac agc 768
Leu Lys Glu Ile Val Glu Arg Val Phe Gln Ser Asn Tyr Phe Asp Ser
245 250 255
act cac aac cac cag aat ggg cta tgt gag gaa gaa gag gca gcc tca 816
Thr His Asn His Gln Asn Gly Leu Cys Glu Glu Glu Glu Ala Ala Ser
260 265 270
gca cct aca gtt gaa gac cag gta gct gaa gct gag cct gag cca gca 864
Ala Pro Thr Val Glu Asp Gln Val Ala Glu Ala Glu Pro Glu Pro Ala
275 280 285
gaa gaa tac act gaa caa agt gaa gtt gaa tca aca gag tat gta aat 912
Glu Glu Tyr Thr Glu Gln Ser Glu Val Glu Ser Thr Glu Tyr Val Asn
290 295 300
aga caa ttt atg gca gaa aca cag ttc agc agt ggt gaa aag gag cag 960
Arg Gln Phe Met Ala Glu Thr Gln Phe Ser Ser Gly Glu Lys Glu Gln
305 310 315 320
gta gat gag tgg acg gtc gaa aca gtg gag gtg gtg aat tca ctc cag 1008
Val Asp Glu Trp Thr Val Glu Thr Val Glu Val Val Asn Ser Leu Gln
325 330 335
cag caa cct cag gct gcg tct cct tca gta cca gag ccc cac tct ttg 1056
Gln Gln Pro Gln Ala Ala Ser Pro Ser Val Pro Glu Pro His Ser Leu
340 345 350
act ccg gtg gct cag gca gat ccc ctt gtg aga aga cag cga gtc cag 1104
Thr Pro Val Ala Gln Ala Asp Pro Leu Val Arg Arg Gln Arg Val Gln
355 360 365
gac ctt atg gcg cag atg cag ggg ccc tat aat ttc ata cag gat tca 1152
Asp Leu Met Ala Gln Met Gln Gly Pro Tyr Asn Phe Ile Gln Asp Ser
370 375 380
atg ctg gat ttt gaa aac cag aca ctc gat cct gcc att gta tct gca 1200
Met Leu Asp Phe Glu Asn Gln Thr Leu Asp Pro Ala Ile Val Ser Ala
385 390 395 400
cag cct atg aat ccg aca caa aac atg gac atg ccc cag ctg gtt tgc 1248
Gln Pro Met Asn Pro Thr Gln Asn Met Asp Met Pro Gln Leu Val Cys
405 410 415
cct cca gtt cat tct gaa tct aga ctt gct caa cct aat caa gtt cct 1296
Pro Pro Val His Ser Glu Ser Arg Leu Ala Gln Pro Asn Gln Val Pro
420 425 430
gta caa cca gaa gct aca cag gtt cct ttg gtt tca tcc aca agt gag 1344
Val Gln Pro Glu Ala Thr Gln Val Pro Leu Val Ser Ser Thr Ser Glu
435 440 445
ggg tat aca gca tct caa ccc ttg tac cag cct tct cat gct aca gag 1392
Gly Tyr Thr Ala Ser Gln Pro Leu Tyr Gln Pro Ser His Ala Thr Glu
450 455 460
caa cga cca caa aag gaa cca att gac cag att cag gca aca atc tct 1440
Gln Arg Pro Gln Lys Glu Pro Ile Asp Gln Ile Gln Ala Thr Ile Ser
465 470 475 480
tta aat aca gac cag act aca gcg tca tca tcc ctt ccg gct gct tct 1488
Leu Asn Thr Asp Gln Thr Thr Ala Ser Ser Ser Leu Pro Ala Ala Ser
485 490 495
cag cct cag gta ttc cag gct ggg aca agc aaa cca tta cat agc agt 1536
Gln Pro Gln Val Phe Gln Ala Gly Thr Ser Lys Pro Leu His Ser Ser
500 505 510
gga atc aat gta aat gca gct cca ttc caa tcc atg caa acg gtg ttc 1584
Gly Ile Asn Val Asn Ala Ala Pro Phe Gln Ser Met Gln Thr Val Phe
515 520 525
aat atg aat gcc cca gtt cct cct gtt aat gaa cca gaa act ttg aaa 1632
Asn Met Asn Ala Pro Val Pro Pro Val Asn Glu Pro Glu Thr Leu Lys
530 535 540
caa caa aat cag tac cag gcc agt tat aac cag agc ttt tct agt cag 1680
Gln Gln Asn Gln Tyr Gln Ala Ser Tyr Asn Gln Ser Phe Ser Ser Gln
545 550 555 560
cct cac caa gta gaa caa aca gac ctt cag caa gaa cag ctt caa aca 1728
Pro His Gln Val Glu Gln Thr Asp Leu Gln Gln Glu Gln Leu Gln Thr
565 570 575
gtg gtt ggc act tac cat ggt tcc cag gac cag ccc cac caa gtg act 1776
Val Val Gly Thr Tyr His Gly Ser Gln Asp Gln Pro His Gln Val Thr
580 585 590
ggt aac cat cag cag cct ccc cag cag aac act gga ttt cca cgt agc 1824
Gly Asn His Gln Gln Pro Pro Gln Gln Asn Thr Gly Phe Pro Arg Ser
595 600 605
agt cag ccc tat tac aat agt cgt ggt gtg tct cgt ggt ggt tcc cgt 1872
Ser Gln Pro Tyr Tyr Asn Ser Arg Gly Val Ser Arg Gly Gly Ser Arg
610 615 620
ggt gct aga ggc tta atg aat gga tac agg ggc cct gcc aat gga ttc 1920
Gly Ala Arg Gly Leu Met Asn Gly Tyr Arg Gly Pro Ala Asn Gly Phe
625 630 635 640
aga gga gga tat gat ggt tac cgc cct tca ttc tct aac act cca aac 1968
Arg Gly Gly Tyr Asp Gly Tyr Arg Pro Ser Phe Ser Asn Thr Pro Asn
645 650 655
agt ggt tat aca cag tct cag ttc agt gct ccc cgg gac tac tct ggc 2016
Ser Gly Tyr Thr Gln Ser Gln Phe Ser Ala Pro Arg Asp Tyr Ser Gly
660 665 670
tat cag cgg gat gga tat cag cag aat ttc aag cga ggc tct ggg cag 2064
Tyr Gln Arg Asp Gly Tyr Gln Gln Asn Phe Lys Arg Gly Ser Gly Gln
675 680 685
agt gga cca cgg gga gcc cca cga ggt aat att ttg tgg tgg tga 2109
Ser Gly Pro Arg Gly Ala Pro Arg Gly Asn Ile Leu Trp Trp
690 695 700
tcctagctcc taagtggagc ttctgttctg gccttggaag agctgttcca tagtctgcat 2169
gtaggttaca tgttaggaat acatttatca ttaccagact tgttgctagg gattaaatga 2229
aatgctctgt ttctaaaact tctcttgaac ccaaatttaa ttttttgaat gactttccct 2289
gttactatat aaattgtctt gaaaactaga acatttctcc tcctcagaaa aagtgttttt 2349
ccaactgcaa attatttttc aggtcctaaa acctgctaaa tgtttttagg aagtacttac 2409
tgaaacattt ttgtaagaca tttttggaat gagattgaac atttatataa atttattatt 2469
attcctcttt catttttgaa catgcatatt atattttagg gtcagaaatc ctttaatggc 2529
caaataagcc atagttacat ttagagaacc atttagaagt gatagaacta actgaaattt 2589
caatgccttt ggatcattaa tagcgatata aatttcaaat tgtttctgac ttttaaataa 2649
aacatccaaa atcctaacta acttcctgaa ctatatttaa aaattacagg tttaaggagt 2709
ttctggtttt ttttctctta ccataggaaa actgtttcct gtttggccag gaagtcaacc 2769
tgtgtaataa ttagaagtag catttcatat gatctgaagt tctaaatggt tctctgattt 2829
aagggaagtt aaattgaata ggtttcctct agttattggc cataacatgt ataaaatgta 2889
tattaaggag gaatacaaag tactttgatt tcaatgctag tagaaactgg ccagcaaaaa 2949
ggtgcatttt atttttaaat taatggatca cttgggaatt actgacttga agtatcaaag 3009
gatatttgca tgtgaatgtg ggttatgttc tttctcacct tgtagcatat tctatgaaag 3069
ttgagttgac tggtagctaa aaatctgttt taacagcatg taaaaagtta ttttatctgt 3129
tacaagtcat tatacaattt tgaatgttat gtagtttctt tttaacagtt taggtaacaa 3189
ggtctgtttt tcattctggt gcttttatta attttgatag tatgatgtta cttactactg 3249
aaatgtaagc tagagtgtac actagaatgt aagctccatg agagcaggta ccttgtctgt 3309
cttcactgct gtatctattt ccaacgcctg atgacagtgc ctgacacata gtaggcactc 3369
aataaatact tgttgaatga atgaatgaat gagtactggt ggaatactcc attagctcta 3429
ctcttctttt agctagagaa catgagcaaa tttgcgcatg acaacttcca ggacaggtga 3489
acactgaaga attgacctct taaacctaat aatgtggtga caagctgccc acatgcttct 3549
tgacttcaga tgaaaatctg cttgaaggca aagcaaataa tatttgaaag aaaaaccaaa 3609
tgccattttt gtcttctagg tcgtggaggg cccccaagac ccaacagagg gatgccgcaa 3669
atgaacactc agcaagtgaa ttaatctgat tcacaggatt atgtttaaac gccaaaaaca 3729
cactggccag tgtaccataa tatgttacca gaagagttat tatctatttg ttctcccttt 3789
caggaaactt attgtaaagg gactgttttc atcccataaa gacaggacta caattgtcag 3849
ctttatatta cctggatatg gaaggaaact atttttattc tgcatgttct tcctaagcgt 3909
catcttgagc cttgcacatg atactcagat tcctcaccct tgcttaggag taaaacataa 3969
tacactttac agggtgatat ctccatagtt atttgaagtg gcttggaaaa agcaagatta 4029
acttctgaca ttggataaaa atcaacaaat cagccctaga gttattcaaa tggtaattga 4089
caaaaactaa aatatttccc ttcgagaagg agtggaatgt ggtttggcag aacaactgca 4149
tttcacagct tttccggtta aattggagca ctaaacgttt agatgcatac caaattatgc 4209
atgggccctt aatataaaag gctggctacc agctttgaca cagcactatt catcctctgg 4269
ccaaacaact gtggttaaac aacacatgta aattgctttt taacagctga tactataata 4329
agacaaagcc aaaatgcaaa aattgggctt tgattggcac tttttgaaaa atatgcaaca 4389
aatatgggat gtaatctgga tggccgcttc tgtacttaat gtgaagtatt tagatacctt 4449
tttgaacact taacagtttc ttctgacaat gacttttgta aggattggta ctatctatca 4509
ttccttataa tgtacattgt ctgtcactaa tcctcagatc ttgctgtatt gtcacctaaa 4569
ttggtacagg tactgatgaa aatatctaat ggataatcat aacactcttg gtcacatgtt 4629
tttcctgcag cctgaaggtt tttaaaagaa aaagatatca aatgcctgct gctaccaccc 4689
ttttaaattg ctatcttttg aaaagcacca gtatgtgttt tagattgatt tccctatttt 4749
agggaaatga cagacagtag tttcagttct gatggtataa gcaaaacaaa taaaacatgt 4809
ttataaaagt tgtatcttga aacactggtg ttcaacagct agcagcttat gtggttcacc 4869
ccatgcattg ttagtgtttc agattttatg gttatctcca gcagctgttt ctgtagtact 4929
tgcatttatc 4939
<210> 10
<211> 702
<212> PRT
<213> 犬(Canis familiaris)
<400> 10
Met Pro Ser Ala Thr Ser Leu Ser Gly Ser Gly Ser Lys Ser Ser Gly
1 5 10 15
Pro Pro Pro Pro Ser Gly Ser Ser Gly Ser Glu Ala Ala Ala Ala Ala
20 25 30
Gly Ala Ala Gly Ala Ala Gly Ala Gly Ala Ala Ala Pro Ala Ser Gln
35 40 45
His Pro Ala Thr Gly Thr Gly Ala Val Gln Thr Glu Ala Met Lys Gln
50 55 60
Ile Leu Gly Val Ile Asp Lys Lys Leu Arg Asn Leu Glu Lys Lys Lys
65 70 75 80
Gly Lys Leu Asp Asp Tyr Gln Glu Arg Met Asn Lys Gly Glu Arg Leu
85 90 95
Asn Gln Asp Gln Leu Asp Ala Val Ser Lys Tyr Gln Glu Val Thr Asn
100 105 110
Asn Leu Glu Phe Ala Lys Glu Leu Gln Arg Ser Phe Met Ala Leu Ser
115 120 125
Gln Asp Ile Gln Lys Thr Ile Lys Lys Thr Ala Arg Arg Glu Gln Leu
130 135 140
Met Arg Glu Glu Ala Glu Gln Lys Arg Leu Lys Thr Val Leu Glu Leu
145 150 155 160
Gln Tyr Val Leu Asp Lys Leu Gly Asp Asp Glu Val Arg Thr Asp Leu
165 170 175
Lys Gln Gly Leu Asn Gly Val Pro Ile Leu Ser Glu Glu Glu Leu Ser
180 185 190
Leu Leu Asp Glu Phe Tyr Lys Leu Ala Asp Pro Glu Arg Asp Met Ser
195 200 205
Leu Arg Leu Asn Glu Gln Tyr Glu His Ala Ser Ile His Leu Trp Asp
210 215 220
Leu Leu Glu Gly Lys Glu Lys Ser Val Cys Gly Thr Thr Tyr Lys Ala
225 230 235 240
Leu Lys Glu Ile Val Glu Arg Val Phe Gln Ser Asn Tyr Phe Asp Ser
245 250 255
Thr His Asn His Gln Asn Gly Leu Cys Glu Glu Glu Glu Ala Ala Ser
260 265 270
Ala Pro Thr Val Glu Asp Gln Val Ala Glu Ala Glu Pro Glu Pro Ala
275 280 285
Glu Glu Tyr Thr Glu Gln Ser Glu Val Glu Ser Thr Glu Tyr Val Asn
290 295 300
Arg Gln Phe Met Ala Glu Thr Gln Phe Ser Ser Gly Glu Lys Glu Gln
305 310 315 320
Val Asp Glu Trp Thr Val Glu Thr Val Glu Val Val Asn Ser Leu Gln
325 330 335
Gln Gln Pro Gln Ala Ala Ser Pro Ser Val Pro Glu Pro His Ser Leu
340 345 350
Thr Pro Val Ala Gln Ala Asp Pro Leu Val Arg Arg Gln Arg Val Gln
355 360 365
Asp Leu Met Ala Gln Met Gln Gly Pro Tyr Asn Phe Ile Gln Asp Ser
370 375 380
Met Leu Asp Phe Glu Asn Gln Thr Leu Asp Pro Ala Ile Val Ser Ala
385 390 395 400
Gln Pro Met Asn Pro Thr Gln Asn Met Asp Met Pro Gln Leu Val Cys
405 410 415
Pro Pro Val His Ser Glu Ser Arg Leu Ala Gln Pro Asn Gln Val Pro
420 425 430
Val Gln Pro Glu Ala Thr Gln Val Pro Leu Val Ser Ser Thr Ser Glu
435 440 445
Gly Tyr Thr Ala Ser Gln Pro Leu Tyr Gln Pro Ser His Ala Thr Glu
450 455 460
Gln Arg Pro Gln Lys Glu Pro Ile Asp Gln Ile Gln Ala Thr Ile Ser
465 470 475 480
Leu Asn Thr Asp Gln Thr Thr Ala Ser Ser Ser Leu Pro Ala Ala Ser
485 490 495
Gln Pro Gln Val Phe Gln Ala Gly Thr Ser Lys Pro Leu His Ser Ser
500 505 510
Gly Ile Asn Val Asn Ala Ala Pro Phe Gln Ser Met Gln Thr Val Phe
515 520 525
Asn Met Asn Ala Pro Val Pro Pro Val Asn Glu Pro Glu Thr Leu Lys
530 535 540
Gln Gln Asn Gln Tyr Gln Ala Ser Tyr Asn Gln Ser Phe Ser Ser Gln
545 550 555 560
Pro His Gln Val Glu Gln Thr Asp Leu Gln Gln Glu Gln Leu Gln Thr
565 570 575
Val Val Gly Thr Tyr His Gly Ser Gln Asp Gln Pro His Gln Val Thr
580 585 590
Gly Asn His Gln Gln Pro Pro Gln Gln Asn Thr Gly Phe Pro Arg Ser
595 600 605
Ser Gln Pro Tyr Tyr Asn Ser Arg Gly Val Ser Arg Gly Gly Ser Arg
610 615 620
Gly Ala Arg Gly Leu Met Asn Gly Tyr Arg Gly Pro Ala Asn Gly Phe
625 630 635 640
Arg Gly Gly Tyr Asp Gly Tyr Arg Pro Ser Phe Ser Asn Thr Pro Asn
645 650 655
Ser Gly Tyr Thr Gln Ser Gln Phe Ser Ala Pro Arg Asp Tyr Ser Gly
660 665 670
Tyr Gln Arg Asp Gly Tyr Gln Gln Asn Phe Lys Arg Gly Ser Gly Gln
675 680 685
Ser Gly Pro Arg Gly Ala Pro Arg Gly Asn Ile Leu Trp Trp
690 695 700
<210> 11
<211> 3306
<212> DNA
<213> 犬(Canis familiaris)
<220>
<221> CDS
<222> (1)..(2040)
<400> 11
atg ccg tcg gcc acc agc ctc agc gga agc ggc agc aag tcg tcg ggc 48
Met Pro Ser Ala Thr Ser Leu Ser Gly Ser Gly Ser Lys Ser Ser Gly
1 5 10 15
ccg ccg ccc ccg tcg ggt tcc tcc ggg agc gag gcg gcg gcg gcg gcg 96
Pro Pro Pro Pro Ser Gly Ser Ser Gly Ser Glu Ala Ala Ala Ala Ala
20 25 30
ggg gcg gcg ggg gcg gcg ggg gcc ggg gcg gct gcg ccc gcc tcc cag 144
Gly Ala Ala Gly Ala Ala Gly Ala Gly Ala Ala Ala Pro Ala Ser Gln
35 40 45
cac ccc gcg acc ggc acc ggc gct gtc cag acc gag gcc atg aag cag 192
His Pro Ala Thr Gly Thr Gly Ala Val Gln Thr Glu Ala Met Lys Gln
50 55 60
atc ctc ggg gtg atc gac aag aaa ctc cgg aac ctg gag aag aaa aag 240
Ile Leu Gly Val Ile Asp Lys Lys Leu Arg Asn Leu Glu Lys Lys Lys
65 70 75 80
ggc aag ctt gat gat tac cag gaa cga atg aac aaa ggg gaa agg ctt 288
Gly Lys Leu Asp Asp Tyr Gln Glu Arg Met Asn Lys Gly Glu Arg Leu
85 90 95
aat caa gat cag ctg gat gcc gta tct aag tac cag gaa gtc aca aat 336
Asn Gln Asp Gln Leu Asp Ala Val Ser Lys Tyr Gln Glu Val Thr Asn
100 105 110
aac ttg gag ttt gca aaa gaa tta cag agg agt ttc atg gca tta agt 384
Asn Leu Glu Phe Ala Lys Glu Leu Gln Arg Ser Phe Met Ala Leu Ser
115 120 125
caa gat att cag aaa aca ata aag aag act gca cgt cgg gag cag ctt 432
Gln Asp Ile Gln Lys Thr Ile Lys Lys Thr Ala Arg Arg Glu Gln Leu
130 135 140
atg aga gag gaa gcg gaa caa aaa cgt tta aaa act gta ctt gag ctc 480
Met Arg Glu Glu Ala Glu Gln Lys Arg Leu Lys Thr Val Leu Glu Leu
145 150 155 160
cag tat gtt ttg gac aaa ttg gga gat gat gaa gtg aga act gac ctg 528
Gln Tyr Val Leu Asp Lys Leu Gly Asp Asp Glu Val Arg Thr Asp Leu
165 170 175
aag caa ggt ttg aat gga gtg cca ata ttg tct gaa gaa gaa ttg tcg 576
Lys Gln Gly Leu Asn Gly Val Pro Ile Leu Ser Glu Glu Glu Leu Ser
180 185 190
ttg ttg gat gaa ttc tac aaa tta gca gac cct gaa cgg gac atg agc 624
Leu Leu Asp Glu Phe Tyr Lys Leu Ala Asp Pro Glu Arg Asp Met Ser
195 200 205
ttg agg ttg aat gag cag tat gaa cat gct tcc att cac ctg tgg gac 672
Leu Arg Leu Asn Glu Gln Tyr Glu His Ala Ser Ile His Leu Trp Asp
210 215 220
ttg ctg gaa gga aag gaa aag tct gta tgt gga aca acc tat aaa gca 720
Leu Leu Glu Gly Lys Glu Lys Ser Val Cys Gly Thr Thr Tyr Lys Ala
225 230 235 240
cta aag gaa att gtt gag cgt gtt ttc cag tca aat tac ttt gac agc 768
Leu Lys Glu Ile Val Glu Arg Val Phe Gln Ser Asn Tyr Phe Asp Ser
245 250 255
act cac aac cac cag aat ggg cta tgt gag gaa gaa gag gca gcc tca 816
Thr His Asn His Gln Asn Gly Leu Cys Glu Glu Glu Glu Ala Ala Ser
260 265 270
gca cct aca gtt gaa gac cag gta gct gaa gct gag cct gag cca gca 864
Ala Pro Thr Val Glu Asp Gln Val Ala Glu Ala Glu Pro Glu Pro Ala
275 280 285
gaa gaa tac act gaa caa agt gaa gtt gaa tca aca gag tat gta aat 912
Glu Glu Tyr Thr Glu Gln Ser Glu Val Glu Ser Thr Glu Tyr Val Asn
290 295 300
aga caa ttt atg gca gaa aca cag ttc agc agt ggt gaa aag gag cag 960
Arg Gln Phe Met Ala Glu Thr Gln Phe Ser Ser Gly Glu Lys Glu Gln
305 310 315 320
gta gat gag tgg acg gtc gaa aca gtg gag gtg gtg aat tca ctc cag 1008
Val Asp Glu Trp Thr Val Glu Thr Val Glu Val Val Asn Ser Leu Gln
325 330 335
cag caa cct cag gct gcg tct cct tca gta cca gag ccc cac tct ttg 1056
Gln Gln Pro Gln Ala Ala Ser Pro Ser Val Pro Glu Pro His Ser Leu
340 345 350
act ccg gtg gct cag gca gat ccc ctt gtg aga aga cag cga gtc cag 1104
Thr Pro Val Ala Gln Ala Asp Pro Leu Val Arg Arg Gln Arg Val Gln
355 360 365
gac ctt atg gcg cag atg cag ggg ccc tat aat ttc ata cag gat tca 1152
Asp Leu Met Ala Gln Met Gln Gly Pro Tyr Asn Phe Ile Gln Asp Ser
370 375 380
atg ctg gat ttt gaa aac cag aca ctc gat cct gcc att gta tct gca 1200
Met Leu Asp Phe Glu Asn Gln Thr Leu Asp Pro Ala Ile Val Ser Ala
385 390 395 400
cag cct atg aat ccg aca caa aac atg gac atg ccc cag ctg gtt tgc 1248
Gln Pro Met Asn Pro Thr Gln Asn Met Asp Met Pro Gln Leu Val Cys
405 410 415
cct cca gtt cat tct gaa tct aga ctt gct caa cct aat caa gtt cct 1296
Pro Pro Val His Ser Glu Ser Arg Leu Ala Gln Pro Asn Gln Val Pro
420 425 430
gta caa cca gaa gct aca cag gtt cct ttg gtt tca tcc aca agt gag 1344
Val Gln Pro Glu Ala Thr Gln Val Pro Leu Val Ser Ser Thr Ser Glu
435 440 445
ggg tat aca gca tct caa ccc ttg tac cag cct tct cat gct aca gag 1392
Gly Tyr Thr Ala Ser Gln Pro Leu Tyr Gln Pro Ser His Ala Thr Glu
450 455 460
caa cga cca caa aag gaa cca att gac cag att cag gca aca atc tct 1440
Gln Arg Pro Gln Lys Glu Pro Ile Asp Gln Ile Gln Ala Thr Ile Ser
465 470 475 480
tta aat aca gac cag act aca gcg tca tca tcc ctt ccg gct gct tct 1488
Leu Asn Thr Asp Gln Thr Thr Ala Ser Ser Ser Leu Pro Ala Ala Ser
485 490 495
cag cct cag gta ttc cag gct ggg aca agc aaa cca tta cat agc agt 1536
Gln Pro Gln Val Phe Gln Ala Gly Thr Ser Lys Pro Leu His Ser Ser
500 505 510
gga atc aat gta aat gca gct cca ttc caa tcc atg caa acg gtg ttc 1584
Gly Ile Asn Val Asn Ala Ala Pro Phe Gln Ser Met Gln Thr Val Phe
515 520 525
aat atg aat gcc cca gtt cct cct gtt aat gaa cca gaa act ttg aaa 1632
Asn Met Asn Ala Pro Val Pro Pro Val Asn Glu Pro Glu Thr Leu Lys
530 535 540
caa caa aat cag tac cag gcc agt tat aac cag agc ttt tct agt cag 1680
Gln Gln Asn Gln Tyr Gln Ala Ser Tyr Asn Gln Ser Phe Ser Ser Gln
545 550 555 560
cct cac caa gta gaa caa aca gac ctt cag caa gaa cag ctt caa aca 1728
Pro His Gln Val Glu Gln Thr Asp Leu Gln Gln Glu Gln Leu Gln Thr
565 570 575
gtg gtt ggc act tac cat ggt tcc cag gac cag ccc cac caa gtg act 1776
Val Val Gly Thr Tyr His Gly Ser Gln Asp Gln Pro His Gln Val Thr
580 585 590
ggt aac cat cag cag cct ccc cag cag aac act gga ttt cca cgt agc 1824
Gly Asn His Gln Gln Pro Pro Gln Gln Asn Thr Gly Phe Pro Arg Ser
595 600 605
agt cag ccc tat tac aat agt cgt ggt gtg tct cgt ggt ggt tcc cgt 1872
Ser Gln Pro Tyr Tyr Asn Ser Arg Gly Val Ser Arg Gly Gly Ser Arg
610 615 620
ggt gct aga ggc tta atg aat gga tac agg ggc cct gcc aat gga ttc 1920
Gly Ala Arg Gly Leu Met Asn Gly Tyr Arg Gly Pro Ala Asn Gly Phe
625 630 635 640
aga gga gga tat gat ggt tac cgc cct tca ttc tct aac act cca aac 1968
Arg Gly Gly Tyr Asp Gly Tyr Arg Pro Ser Phe Ser Asn Thr Pro Asn
645 650 655
agt ggt tat aca cag tct cag ttc agt gct ccc cgg gac tac tct ggc 2016
Ser Gly Tyr Thr Gln Ser Gln Phe Ser Ala Pro Arg Asp Tyr Ser Gly
660 665 670
tat cag cgg gga tgc cgc aaa tga acactcagca agtgaattaa tctgattcac 2070
Tyr Gln Arg Gly Cys Arg Lys
675
aggattatgt ttaaacgcca aaaacacact ggccagtgta ccataatatg ttaccagaag 2130
agttattatc tatttgttct ccctttcagg aaacttattg taaagggact gttttcatcc 2190
cataaagaca ggactacaat tgtcagcttt atattacctg gatatggaag gaaactattt 2250
ttattctgca tgttcttcct aagcgtcatc ttgagccttg cacatgatac tcagattcct 2310
cacccttgct taggagtaaa acataataca ctttacaggg tgatatctcc atagttattt 2370
gaagtggctt ggaaaaagca agattaactt ctgacattgg ataaaaatca acaaatcagc 2430
cctagagtta ttcaaatggt aattgacaaa aactaaaata tttcccttcg agaaggagtg 2490
gaatgtggtt tggcagaaca actgcatttc acagcttttc cggttaaatt ggagcactaa 2550
acgtttagat gcataccaaa ttatgcatgg gcccttaata taaaaggctg gctaccagct 2610
ttgacacagc actattcatc ctctggccaa acaactgtgg ttaaacaaca catgtaaatt 2670
gctttttaac agctgatact ataataagac aaagccaaaa tgcaaaaatt gggctttgat 2730
tggcactttt tgaaaaatat gcaacaaata tgggatgtaa tctggatggc cgcttctgta 2790
cttaatgtga agtatttaga tacctttttg aacacttaac agtttcttct gacaatgact 2850
tttgtaagga ttggtactat ctatcattcc ttataatgta cattgtctgt cactaatcct 2910
cagatcttgc tgtattgtca cctaaattgg tacaggtact gatgaaaata tctaatggat 2970
aatcataaca ctcttggtca catgtttttc ctgcagcctg aaggttttta aaagaaaaag 3030
atatcaaatg cctgctgcta ccaccctttt aaattgctat cttttgaaaa gcaccagtat 3090
gtgttttaga ttgatttccc tattttaggg aaatgacaga cagtagtttc agttctgatg 3150
gtataagcaa aacaaataaa acatgtttat aaaagttgta tcttgaaaca ctggtgttca 3210
acagctagca gcttatgtgg ttcaccccat gcattgttag tgtttcagat tttatggtta 3270
tctccagcag ctgtttctgt agtacttgca tttatc 3306
<210> 12
<211> 679
<212> PRT
<213> 犬(Canis familiaris)
<400> 12
Met Pro Ser Ala Thr Ser Leu Ser Gly Ser Gly Ser Lys Ser Ser Gly
1 5 10 15
Pro Pro Pro Pro Ser Gly Ser Ser Gly Ser Glu Ala Ala Ala Ala Ala
20 25 30
Gly Ala Ala Gly Ala Ala Gly Ala Gly Ala Ala Ala Pro Ala Ser Gln
35 40 45
His Pro Ala Thr Gly Thr Gly Ala Val Gln Thr Glu Ala Met Lys Gln
50 55 60
Ile Leu Gly Val Ile Asp Lys Lys Leu Arg Asn Leu Glu Lys Lys Lys
65 70 75 80
Gly Lys Leu Asp Asp Tyr Gln Glu Arg Met Asn Lys Gly Glu Arg Leu
85 90 95
Asn Gln Asp Gln Leu Asp Ala Val Ser Lys Tyr Gln Glu Val Thr Asn
100 105 110
Asn Leu Glu Phe Ala Lys Glu Leu Gln Arg Ser Phe Met Ala Leu Ser
115 120 125
Gln Asp Ile Gln Lys Thr Ile Lys Lys Thr Ala Arg Arg Glu Gln Leu
130 135 140
Met Arg Glu Glu Ala Glu Gln Lys Arg Leu Lys Thr Val Leu Glu Leu
145 150 155 160
Gln Tyr Val Leu Asp Lys Leu Gly Asp Asp Glu Val Arg Thr Asp Leu
165 170 175
Lys Gln Gly Leu Asn Gly Val Pro Ile Leu Ser Glu Glu Glu Leu Ser
180 185 190
Leu Leu Asp Glu Phe Tyr Lys Leu Ala Asp Pro Glu Arg Asp Met Ser
195 200 205
Leu Arg Leu Asn Glu Gln Tyr Glu His Ala Ser Ile His Leu Trp Asp
210 215 220
Leu Leu Glu Gly Lys Glu Lys Ser Val Cys Gly Thr Thr Tyr Lys Ala
225 230 235 240
Leu Lys Glu Ile Val Glu Arg Val Phe Gln Ser Asn Tyr Phe Asp Ser
245 250 255
Thr His Asn His Gln Asn Gly Leu Cys Glu Glu Glu Glu Ala Ala Ser
260 265 270
Ala Pro Thr Val Glu Asp Gln Val Ala Glu Ala Glu Pro Glu Pro Ala
275 280 285
Glu Glu Tyr Thr Glu Gln Ser Glu Val Glu Ser Thr Glu Tyr Val Asn
290 295 300
Arg Gln Phe Met Ala Glu Thr Gln Phe Ser Ser Gly Glu Lys Glu Gln
305 310 315 320
Val Asp Glu Trp Thr Val Glu Thr Val Glu Val Val Asn Ser Leu Gln
325 330 335
Gln Gln Pro Gln Ala Ala Ser Pro Ser Val Pro Glu Pro His Ser Leu
340 345 350
Thr Pro Val Ala Gln Ala Asp Pro Leu Val Arg Arg Gln Arg Val Gln
355 360 365
Asp Leu Met Ala Gln Met Gln Gly Pro Tyr Asn Phe Ile Gln Asp Ser
370 375 380
Met Leu Asp Phe Glu Asn Gln Thr Leu Asp Pro Ala Ile Val Ser Ala
385 390 395 400
Gln Pro Met Asn Pro Thr Gln Asn Met Asp Met Pro Gln Leu Val Cys
405 410 415
Pro Pro Val His Ser Glu Ser Arg Leu Ala Gln Pro Asn Gln Val Pro
420 425 430
Val Gln Pro Glu Ala Thr Gln Val Pro Leu Val Ser Ser Thr Ser Glu
435 440 445
Gly Tyr Thr Ala Ser Gln Pro Leu Tyr Gln Pro Ser His Ala Thr Glu
450 455 460
Gln Arg Pro Gln Lys Glu Pro Ile Asp Gln Ile Gln Ala Thr Ile Ser
465 470 475 480
Leu Asn Thr Asp Gln Thr Thr Ala Ser Ser Ser Leu Pro Ala Ala Ser
485 490 495
Gln Pro Gln Val Phe Gln Ala Gly Thr Ser Lys Pro Leu His Ser Ser
500 505 510
Gly Ile Asn Val Asn Ala Ala Pro Phe Gln Ser Met Gln Thr Val Phe
515 520 525
Asn Met Asn Ala Pro Val Pro Pro Val Asn Glu Pro Glu Thr Leu Lys
530 535 540
Gln Gln Asn Gln Tyr Gln Ala Ser Tyr Asn Gln Ser Phe Ser Ser Gln
545 550 555 560
Pro His Gln Val Glu Gln Thr Asp Leu Gln Gln Glu Gln Leu Gln Thr
565 570 575
Val Val Gly Thr Tyr His Gly Ser Gln Asp Gln Pro His Gln Val Thr
580 585 590
Gly Asn His Gln Gln Pro Pro Gln Gln Asn Thr Gly Phe Pro Arg Ser
595 600 605
Ser Gln Pro Tyr Tyr Asn Ser Arg Gly Val Ser Arg Gly Gly Ser Arg
610 615 620
Gly Ala Arg Gly Leu Met Asn Gly Tyr Arg Gly Pro Ala Asn Gly Phe
625 630 635 640
Arg Gly Gly Tyr Asp Gly Tyr Arg Pro Ser Phe Ser Asn Thr Pro Asn
645 650 655
Ser Gly Tyr Thr Gln Ser Gln Phe Ser Ala Pro Arg Asp Tyr Ser Gly
660 665 670
Tyr Gln Arg Gly Cys Arg Lys
675
<210> 13
<211> 2281
<212> DNA
<213> 犬(Canis familiaris)
<220>
<221> CDS
<222> (1)..(2154)
<400> 13
atg ccg tcg gcc acc agc ctc agc gga agc ggc agc aag tcg tcg ggc 48
Met Pro Ser Ala Thr Ser Leu Ser Gly Ser Gly Ser Lys Ser Ser Gly
1 5 10 15
ccg ccg ccc ccg tcg ggt tcc tcc ggg agc gag gcg gcg gcg gcg gcg 96
Pro Pro Pro Pro Ser Gly Ser Ser Gly Ser Glu Ala Ala Ala Ala Ala
20 25 30
ggg gcg gcg ggg gcg gcg ggg gcc ggg gcg gct gcg ccc gcc tcc cag 144
Gly Ala Ala Gly Ala Ala Gly Ala Gly Ala Ala Ala Pro Ala Ser Gln
35 40 45
cac ccc gcg acc ggc acc ggc gct gtc cag acc gag gcc atg aag cag 192
His Pro Ala Thr Gly Thr Gly Ala Val Gln Thr Glu Ala Met Lys Gln
50 55 60
atc ctc ggg gtg atc gac aag aaa ctc cgg aac ctg gag aag aaa aag 240
Ile Leu Gly Val Ile Asp Lys Lys Leu Arg Asn Leu Glu Lys Lys Lys
65 70 75 80
ggc aag ctt gat gat tac cag gaa cga atg aac aaa ggg gaa agg ctt 288
Gly Lys Leu Asp Asp Tyr Gln Glu Arg Met Asn Lys Gly Glu Arg Leu
85 90 95
aat caa gat cag ctg gat gcc gta tct aag tac cag gaa gtc aca aat 336
Asn Gln Asp Gln Leu Asp Ala Val Ser Lys Tyr Gln Glu Val Thr Asn
100 105 110
aac ttg gag ttt gca aaa gaa tta cag agg agt ttc atg gca tta agt 384
Asn Leu Glu Phe Ala Lys Glu Leu Gln Arg Ser Phe Met Ala Leu Ser
115 120 125
caa gat att cag aaa aca ata aag aag act gca cgt cgg gag cag ctt 432
Gln Asp Ile Gln Lys Thr Ile Lys Lys Thr Ala Arg Arg Glu Gln Leu
130 135 140
atg aga gag gaa gcg gaa caa aaa cgt tta aaa act gta ctt gag ctc 480
Met Arg Glu Glu Ala Glu Gln Lys Arg Leu Lys Thr Val Leu Glu Leu
145 150 155 160
cag tat gtt ttg gac aaa ttg gga gat gat gaa gtg aga act gac ctg 528
Gln Tyr Val Leu Asp Lys Leu Gly Asp Asp Glu Val Arg Thr Asp Leu
165 170 175
aag caa ggt ttg aat gga gtg cca ata ttg tct gaa gaa gaa ttg tcg 576
Lys Gln Gly Leu Asn Gly Val Pro Ile Leu Ser Glu Glu Glu Leu Ser
180 185 190
ttg ttg gat gaa ttc tac aaa tta gca gac cct gaa cgg gac atg agc 624
Leu Leu Asp Glu Phe Tyr Lys Leu Ala Asp Pro Glu Arg Asp Met Ser
195 200 205
ttg agg ttg aat gag cag tat gaa cat gct tcc att cac ctg tgg gac 672
Leu Arg Leu Asn Glu Gln Tyr Glu His Ala Ser Ile His Leu Trp Asp
210 215 220
ttg ctg gaa gga aag gaa aag tct gta tgt gga aca acc tat aaa gca 720
Leu Leu Glu Gly Lys Glu Lys Ser Val Cys Gly Thr Thr Tyr Lys Ala
225 230 235 240
cta aag gaa att gtt gag cgt gtt ttc cag tca aat tac ttt gac agc 768
Leu Lys Glu Ile Val Glu Arg Val Phe Gln Ser Asn Tyr Phe Asp Ser
245 250 255
act cac aac cac cag aat ggg cta tgt gag gaa gaa gag gca gcc tca 816
Thr His Asn His Gln Asn Gly Leu Cys Glu Glu Glu Glu Ala Ala Ser
260 265 270
gca cct aca gtt gaa gac cag gta gct gaa gct gag cct gag cca gca 864
Ala Pro Thr Val Glu Asp Gln Val Ala Glu Ala Glu Pro Glu Pro Ala
275 280 285
gaa gaa tac act gaa caa agt gaa gtt gaa tca aca gag tat gta aat 912
Glu Glu Tyr Thr Glu Gln Ser Glu Val Glu Ser Thr Glu Tyr Val Asn
290 295 300
aga caa ttt atg gca gaa aca cag ttc agc agt ggt gaa aag gag cag 960
Arg Gln Phe Met Ala Glu Thr Gln Phe Ser Ser Gly Glu Lys Glu Gln
305 310 315 320
gta gat gag tgg acg gtc gaa aca gtg gag gtg gtg aat tca ctc cag 1008
Val Asp Glu Trp Thr Val Glu Thr Val Glu Val Val Asn Ser Leu Gln
325 330 335
cag caa cct cag gct gcg tct cct tca gta cca gag ccc cac tct ttg 1056
Gln Gln Pro Gln Ala Ala Ser Pro Ser Val Pro Glu Pro His Ser Leu
340 345 350
act ccg gtg gct cag gca gat ccc ctt gtg aga aga cag cga gtc cag 1104
Thr Pro Val Ala Gln Ala Asp Pro Leu Val Arg Arg Gln Arg Val Gln
355 360 365
gac ctt atg gcg cag atg cag ggg ccc tat aat ttc ata cag gat tca 1152
Asp Leu Met Ala Gln Met Gln Gly Pro Tyr Asn Phe Ile Gln Asp Ser
370 375 380
atg ctg gat ttt gaa aac cag aca ctc gat cct gcc att gta tct gca 1200
Met Leu Asp Phe Glu Asn Gln Thr Leu Asp Pro Ala Ile Val Ser Ala
385 390 395 400
cag cct atg aat ccg aca caa aac atg gac atg ccc cag ctg gtt tgc 1248
Gln Pro Met Asn Pro Thr Gln Asn Met Asp Met Pro Gln Leu Val Cys
405 410 415
cct cca gtt cat tct gaa tct aga ctt gct caa cct aat caa gtt cct 1296
Pro Pro Val His Ser Glu Ser Arg Leu Ala Gln Pro Asn Gln Val Pro
420 425 430
gta caa cca gaa gct aca cag gtt cct ttg gtt tca tcc aca agt gag 1344
Val Gln Pro Glu Ala Thr Gln Val Pro Leu Val Ser Ser Thr Ser Glu
435 440 445
ggg tat aca gca tct caa ccc ttg tac cag cct tct cat gct aca gag 1392
Gly Tyr Thr Ala Ser Gln Pro Leu Tyr Gln Pro Ser His Ala Thr Glu
450 455 460
caa cga cca caa aag gaa cca att gac cag att cag gca aca atc tct 1440
Gln Arg Pro Gln Lys Glu Pro Ile Asp Gln Ile Gln Ala Thr Ile Ser
465 470 475 480
tta aat aca gac cag act aca gcg tca tca tcc ctt ccg gct gct tct 1488
Leu Asn Thr Asp Gln Thr Thr Ala Ser Ser Ser Leu Pro Ala Ala Ser
485 490 495
cag cct cag gta ttc cag gct ggg aca agc aaa cca tta cat agc agt 1536
Gln Pro Gln Val Phe Gln Ala Gly Thr Ser Lys Pro Leu His Ser Ser
500 505 510
gga atc aat gta aat gca gct cca ttc caa tcc atg caa acg gtg ttc 1584
Gly Ile Asn Val Asn Ala Ala Pro Phe Gln Ser Met Gln Thr Val Phe
515 520 525
aat atg aat gcc cca gtt cct cct gtt aat gaa cca gaa act ttg aaa 1632
Asn Met Asn Ala Pro Val Pro Pro Val Asn Glu Pro Glu Thr Leu Lys
530 535 540
caa caa aat cag tac cag gcc agt tat aac cag agc ttt tct agt cag 1680
Gln Gln Asn Gln Tyr Gln Ala Ser Tyr Asn Gln Ser Phe Ser Ser Gln
545 550 555 560
cct cac caa gta gaa caa aca gac ctt cag caa gaa cag ctt caa aca 1728
Pro His Gln Val Glu Gln Thr Asp Leu Gln Gln Glu Gln Leu Gln Thr
565 570 575
gtg gtt ggc act tac cat ggt tcc cag gac cag ccc cac caa gtg act 1776
Val Val Gly Thr Tyr His Gly Ser Gln Asp Gln Pro His Gln Val Thr
580 585 590
ggt aac cat cag cag cct ccc cag cag aac act gga ttt cca cgt agc 1824
Gly Asn His Gln Gln Pro Pro Gln Gln Asn Thr Gly Phe Pro Arg Ser
595 600 605
agt cag ccc tat tac aat agt cgt ggt gtg tct cgt ggt ggt tcc cgt 1872
Ser Gln Pro Tyr Tyr Asn Ser Arg Gly Val Ser Arg Gly Gly Ser Arg
610 615 620
ggt gct aga ggc tta atg aat gga tac agg ggc cct gcc aat gga ttc 1920
Gly Ala Arg Gly Leu Met Asn Gly Tyr Arg Gly Pro Ala Asn Gly Phe
625 630 635 640
aga gga gga tat gat ggt tac cgc cct tca ttc tct aac act cca aac 1968
Arg Gly Gly Tyr Asp Gly Tyr Arg Pro Ser Phe Ser Asn Thr Pro Asn
645 650 655
agt ggt tat aca cag tct cag ttc agt gct ccc cgg gac tac tct ggc 2016
Ser Gly Tyr Thr Gln Ser Gln Phe Ser Ala Pro Arg Asp Tyr Ser Gly
660 665 670
tat cag cgg gat gga tat cag cag aat ttc aag cga ggc tct ggg cag 2064
Tyr Gln Arg Asp Gly Tyr Gln Gln Asn Phe Lys Arg Gly Ser Gly Gln
675 680 685
agt gga cca cgg gga gcc cca cga ggt cgt gga ggg ccc cca aga ccc 2112
Ser Gly Pro Arg Gly Ala Pro Arg Gly Arg Gly Gly Pro Pro Arg Pro
690 695 700
aac aga ggg atg ccg caa atg aac act cag caa gtg aat taa 2154
Asn Arg Gly Met Pro Gln Met Asn Thr Gln Gln Val Asn
705 710 715
tctgattcac aggattatgt ttaaacgcca aaaacacact ggccagtgta ccataatatg 2214
ttaccagaag agttattatc tatttggact gttttcatcc cataaagaca ggactacaat 2274
tgtcagc 2281
<210> 14
<211> 717
<212> PRT
<213> 犬(Canis familiaris)
<400> 14
Met Pro Ser Ala Thr Ser Leu Ser Gly Ser Gly Ser Lys Ser Ser Gly
1 5 10 15
Pro Pro Pro Pro Ser Gly Ser Ser Gly Ser Glu Ala Ala Ala Ala Ala
20 25 30
Gly Ala Ala Gly Ala Ala Gly Ala Gly Ala Ala Ala Pro Ala Ser Gln
35 40 45
His Pro Ala Thr Gly Thr Gly Ala Val Gln Thr Glu Ala Met Lys Gln
50 55 60
Ile Leu Gly Val Ile Asp Lys Lys Leu Arg Asn Leu Glu Lys Lys Lys
65 70 75 80
Gly Lys Leu Asp Asp Tyr Gln Glu Arg Met Asn Lys Gly Glu Arg Leu
85 90 95
Asn Gln Asp Gln Leu Asp Ala Val Ser Lys Tyr Gln Glu Val Thr Asn
100 105 110
Asn Leu Glu Phe Ala Lys Glu Leu Gln Arg Ser Phe Met Ala Leu Ser
115 120 125
Gln Asp Ile Gln Lys Thr Ile Lys Lys Thr Ala Arg Arg Glu Gln Leu
130 135 140
Met Arg Glu Glu Ala Glu Gln Lys Arg Leu Lys Thr Val Leu Glu Leu
145 150 155 160
Gln Tyr Val Leu Asp Lys Leu Gly Asp Asp Glu Val Arg Thr Asp Leu
165 170 175
Lys Gln Gly Leu Asn Gly Val Pro Ile Leu Ser Glu Glu Glu Leu Ser
180 185 190
Leu Leu Asp Glu Phe Tyr Lys Leu Ala Asp Pro Glu Arg Asp Met Ser
195 200 205
Leu Arg Leu Asn Glu Gln Tyr Glu His Ala Ser Ile His Leu Trp Asp
210 215 220
Leu Leu Glu Gly Lys Glu Lys Ser Val Cys Gly Thr Thr Tyr Lys Ala
225 230 235 240
Leu Lys Glu Ile Val Glu Arg Val Phe Gln Ser Asn Tyr Phe Asp Ser
245 250 255
Thr His Asn His Gln Asn Gly Leu Cys Glu Glu Glu Glu Ala Ala Ser
260 265 270
Ala Pro Thr Val Glu Asp Gln Val Ala Glu Ala Glu Pro Glu Pro Ala
275 280 285
Glu Glu Tyr Thr Glu Gln Ser Glu Val Glu Ser Thr Glu Tyr Val Asn
290 295 300
Arg Gln Phe Met Ala Glu Thr Gln Phe Ser Ser Gly Glu Lys Glu Gln
305 310 315 320
Val Asp Glu Trp Thr Val Glu Thr Val Glu Val Val Asn Ser Leu Gln
325 330 335
Gln Gln Pro Gln Ala Ala Ser Pro Ser Val Pro Glu Pro His Ser Leu
340 345 350
Thr Pro Val Ala Gln Ala Asp Pro Leu Val Arg Arg Gln Arg Val Gln
355 360 365
Asp Leu Met Ala Gln Met Gln Gly Pro Tyr Asn Phe Ile Gln Asp Ser
370 375 380
Met Leu Asp Phe Glu Asn Gln Thr Leu Asp Pro Ala Ile Val Ser Ala
385 390 395 400
Gln Pro Met Asn Pro Thr Gln Asn Met Asp Met Pro Gln Leu Val Cys
405 410 415
Pro Pro Val His Ser Glu Ser Arg Leu Ala Gln Pro Asn Gln Val Pro
420 425 430
Val Gln Pro Glu Ala Thr Gln Val Pro Leu Val Ser Ser Thr Ser Glu
435 440 445
Gly Tyr Thr Ala Ser Gln Pro Leu Tyr Gln Pro Ser His Ala Thr Glu
450 455 460
Gln Arg Pro Gln Lys Glu Pro Ile Asp Gln Ile Gln Ala Thr Ile Ser
465 470 475 480
Leu Asn Thr Asp Gln Thr Thr Ala Ser Ser Ser Leu Pro Ala Ala Ser
485 490 495
Gln Pro Gln Val Phe Gln Ala Gly Thr Ser Lys Pro Leu His Ser Ser
500 505 510
Gly Ile Asn Val Asn Ala Ala Pro Phe Gln Ser Met Gln Thr Val Phe
515 520 525
Asn Met Asn Ala Pro Val Pro Pro Val Asn Glu Pro Glu Thr Leu Lys
530 535 540
Gln Gln Asn Gln Tyr Gln Ala Ser Tyr Asn Gln Ser Phe Ser Ser Gln
545 550 555 560
Pro His Gln Val Glu Gln Thr Asp Leu Gln Gln Glu Gln Leu Gln Thr
565 570 575
Val Val Gly Thr Tyr His Gly Ser Gln Asp Gln Pro His Gln Val Thr
580 585 590
Gly Asn His Gln Gln Pro Pro Gln Gln Asn Thr Gly Phe Pro Arg Ser
595 600 605
Ser Gln Pro Tyr Tyr Asn Ser Arg Gly Val Ser Arg Gly Gly Ser Arg
610 615 620
Gly Ala Arg Gly Leu Met Asn Gly Tyr Arg Gly Pro Ala Asn Gly Phe
625 630 635 640
Arg Gly Gly Tyr Asp Gly Tyr Arg Pro Ser Phe Ser Asn Thr Pro Asn
645 650 655
Ser Gly Tyr Thr Gln Ser Gln Phe Ser Ala Pro Arg Asp Tyr Ser Gly
660 665 670
Tyr Gln Arg Asp Gly Tyr Gln Gln Asn Phe Lys Arg Gly Ser Gly Gln
675 680 685
Ser Gly Pro Arg Gly Ala Pro Arg Gly Arg Gly Gly Pro Pro Arg Pro
690 695 700
Asn Arg Gly Met Pro Gln Met Asn Thr Gln Gln Val Asn
705 710 715
<210> 15
<211> 3386
<212> DNA
<213> 牛(Bos taurus)
<220>
<221> CDS
<222> (82)..(2208)
<400> 15
cgcgtctcgc cccgtccacc gattgactcg ccgctcttgt ccttcctccc gctctttctt 60
ctctcccctt acggtttcaa g atg cct tcg gcc acc agc cac agc gga agc 111
Met Pro Ser Ala Thr Ser His Ser Gly Ser
1 5 10
ggc agc aag tcg tcc gga ccg cca ccg ccg tcg ggt tcc tcc ggg aat 159
Gly Ser Lys Ser Ser Gly Pro Pro Pro Pro Ser Gly Ser Ser Gly Asn
15 20 25
gag gcg ggg gcc ggg gcc gcc gcg ccg gct tcc caa cac ccc atg acc 207
Glu Ala Gly Ala Gly Ala Ala Ala Pro Ala Ser Gln His Pro Met Thr
30 35 40
ggc acc ggg gct gtc cag acc gag gcc atg aag cag att ctc ggg gtg 255
Gly Thr Gly Ala Val Gln Thr Glu Ala Met Lys Gln Ile Leu Gly Val
45 50 55
atc gac aag aaa ctt cgg aac ctg gag aag aaa aag ggc aag ctt gat 303
Ile Asp Lys Lys Leu Arg Asn Leu Glu Lys Lys Lys Gly Lys Leu Asp
60 65 70
gat tat cag gaa cga atg aac aaa ggg gaa agg ctt aat caa gat cag 351
Asp Tyr Gln Glu Arg Met Asn Lys Gly Glu Arg Leu Asn Gln Asp Gln
75 80 85 90
ctg gat gcc gtg tct aag tac cag gaa gtc aca aat aac ttg gag ttt 399
Leu Asp Ala Val Ser Lys Tyr Gln Glu Val Thr Asn Asn Leu Glu Phe
95 100 105
gca aaa gaa tta cag agg agt ttc atg gca tta agc caa gat att cag 447
Ala Lys Glu Leu Gln Arg Ser Phe Met Ala Leu Ser Gln Asp Ile Gln
110 115 120
aaa aca ata aag aag aca gca cgt cgg gag cag ctt atg aga gag gaa 495
Lys Thr Ile Lys Lys Thr Ala Arg Arg Glu Gln Leu Met Arg Glu Glu
125 130 135
gct gaa cag aaa cgt tta aaa aca gta ctt gag ctg cag tat gtt ttg 543
Ala Glu Gln Lys Arg Leu Lys Thr Val Leu Glu Leu Gln Tyr Val Leu
140 145 150
gac aaa cta gga gat gat gaa gtg aga act gac ctg aag caa ggt ttg 591
Asp Lys Leu Gly Asp Asp Glu Val Arg Thr Asp Leu Lys Gln Gly Leu
155 160 165 170
aat gga gtg cca ata ttg tct gaa gag gag ttg tcg ttg tta gat gag 639
Asn Gly Val Pro Ile Leu Ser Glu Glu Glu Leu Ser Leu Leu Asp Glu
175 180 185
ttc tac aaa tta gca gac cct gaa cga gac atg agc ttg agg ttg aat 687
Phe Tyr Lys Leu Ala Asp Pro Glu Arg Asp Met Ser Leu Arg Leu Asn
190 195 200
gag cag tat gaa cat gcc tcc att cac ctg tgg gac ttg ctg gaa gga 735
Glu Gln Tyr Glu His Ala Ser Ile His Leu Trp Asp Leu Leu Glu Gly
205 210 215
aag gaa aaa cct gta tgt gga aca act tat aaa gct cta aag gaa att 783
Lys Glu Lys Pro Val Cys Gly Thr Thr Tyr Lys Ala Leu Lys Glu Ile
220 225 230
gtt gag cgt gtt ttc cag tca aac tac ttt gac agc acc cac aac cac 831
Val Glu Arg Val Phe Gln Ser Asn Tyr Phe Asp Ser Thr His Asn His
235 240 245 250
cag aat ggt ctg tgt gag gaa gag gag gca gcc tca gca cct aca gtt 879
Gln Asn Gly Leu Cys Glu Glu Glu Glu Ala Ala Ser Ala Pro Thr Val
255 260 265
gaa gac cag gca gct gaa gct gaa cct gag cca gtg gaa gaa tat act 927
Glu Asp Gln Ala Ala Glu Ala Glu Pro Glu Pro Val Glu Glu Tyr Thr
270 275 280
gaa caa aat gag gtt gaa tca aca gag tat gta aat aga caa ttt atg 975
Glu Gln Asn Glu Val Glu Ser Thr Glu Tyr Val Asn Arg Gln Phe Met
285 290 295
gca gaa aca cag ttc agc agt ggt gaa aag gag cag gta gat gat tgg 1023
Ala Glu Thr Gln Phe Ser Ser Gly Glu Lys Glu Gln Val Asp Asp Trp
300 305 310
aca gtt gaa aca gtt gag gtg gta aat tca ctc cag cag caa cct cag 1071
Thr Val Glu Thr Val Glu Val Val Asn Ser Leu Gln Gln Gln Pro Gln
315 320 325 330
gct gca tct cct tca gta cca gaa ccc cac tct ttg acc cca gtg gct 1119
Ala Ala Ser Pro Ser Val Pro Glu Pro His Ser Leu Thr Pro Val Ala
335 340 345
caa gcc gat ccc ctc gtg aga aga cag cga gta cag gac ctt atg gca 1167
Gln Ala Asp Pro Leu Val Arg Arg Gln Arg Val Gln Asp Leu Met Ala
350 355 360
caa atg cag ggg ccc tat aat ttc ata cag gat tca atg ttg gat ttt 1215
Gln Met Gln Gly Pro Tyr Asn Phe Ile Gln Asp Ser Met Leu Asp Phe
365 370 375
gaa aac cag aca ctt gat cct gcc att gta tct gca cag ccg atg aat 1263
Glu Asn Gln Thr Leu Asp Pro Ala Ile Val Ser Ala Gln Pro Met Asn
380 385 390
cca gca cag aac atg gac ata ccc cag ctg gtt tgc cct cca gtt cat 1311
Pro Ala Gln Asn Met Asp Ile Pro Gln Leu Val Cys Pro Pro Val His
395 400 405 410
tct gaa tct aga ctt gct caa cct aat caa gtt tct gta cag cca gaa 1359
Ser Glu Ser Arg Leu Ala Gln Pro Asn Gln Val Ser Val Gln Pro Glu
415 420 425
gct aca cag gtt cct ttg gtt tca tcc aca agt gag gga tat aca gca 1407
Ala Thr Gln Val Pro Leu Val Ser Ser Thr Ser Glu Gly Tyr Thr Ala
430 435 440
tct caa ccc ttg tac caa cct tct cat gct act gac caa cga cca caa 1455
Ser Gln Pro Leu Tyr Gln Pro Ser His Ala Thr Asp Gln Arg Pro Gln
445 450 455
aag gaa ccg att gat cag att cag gcg acg atc tct tta aat aca gac 1503
Lys Glu Pro Ile Asp Gln Ile Gln Ala Thr Ile Ser Leu Asn Thr Asp
460 465 470
cag act aca gca tca tca tcc ctt cct gct gct tct cag cct caa gtg 1551
Gln Thr Thr Ala Ser Ser Ser Leu Pro Ala Ala Ser Gln Pro Gln Val
475 480 485 490
ttc cag gct ggg aca agc aaa cct tta cat agc agt gga atc aat gta 1599
Phe Gln Ala Gly Thr Ser Lys Pro Leu His Ser Ser Gly Ile Asn Val
495 500 505
aat gca gct cca ttc caa tcc atg caa acg gta ttc aat atg aat gcc 1647
Asn Ala Ala Pro Phe Gln Ser Met Gln Thr Val Phe Asn Met Asn Ala
510 515 520
cca gtt cct cct gtt aat gaa cca gaa act tta aaa cag caa aat cag 1695
Pro Val Pro Pro Val Asn Glu Pro Glu Thr Leu Lys Gln Gln Asn Gln
525 530 535
tac cag gcc agt tac aac cag agc ttt tcc agt cag cct cac caa gta 1743
Tyr Gln Ala Ser Tyr Asn Gln Ser Phe Ser Ser Gln Pro His Gln Val
540 545 550
gaa caa aca gag ctt cag caa gaa cag ctt caa aca gtg gtt ggc act 1791
Glu Gln Thr Glu Leu Gln Gln Glu Gln Leu Gln Thr Val Val Gly Thr
555 560 565 570
tat cat ggt tct cag gac cag ccc cat caa gtg act ggt aac cac cag 1839
Tyr His Gly Ser Gln Asp Gln Pro His Gln Val Thr Gly Asn His Gln
575 580 585
cag cct cct cag cag aac act gga ttt cca cgt agc aat cag ccc tat 1887
Gln Pro Pro Gln Gln Asn Thr Gly Phe Pro Arg Ser Asn Gln Pro Tyr
590 595 600
tac aac agt cgt ggt gtg tct cgt gga ggt tcc cgt ggt gct aga ggc 1935
Tyr Asn Ser Arg Gly Val Ser Arg Gly Gly Ser Arg Gly Ala Arg Gly
605 610 615
ttg atg aat gga tac aga gga cct gct aat gga ttc aga gga gga tat 1983
Leu Met Asn Gly Tyr Arg Gly Pro Ala Asn Gly Phe Arg Gly Gly Tyr
620 625 630
gat ggt tac cgc cct tca ttc tct act aac act cca aac agt ggt tat 2031
Asp Gly Tyr Arg Pro Ser Phe Ser Thr Asn Thr Pro Asn Ser Gly Tyr
635 640 645 650
aca caa tct caa ttc agt gct ccc cgg gac tac tct ggc tat cag cgg 2079
Thr Gln Ser Gln Phe Ser Ala Pro Arg Asp Tyr Ser Gly Tyr Gln Arg
655 660 665
gat gga tat cag cag aat ttc aag cga ggc tct ggg cag agt gga cca 2127
Asp Gly Tyr Gln Gln Asn Phe Lys Arg Gly Ser Gly Gln Ser Gly Pro
670 675 680
cgg gga gcc cca cga ggt cgt gga ggg ccc cca aga ccc aac aga ggg 2175
Arg Gly Ala Pro Arg Gly Arg Gly Gly Pro Pro Arg Pro Asn Arg Gly
685 690 695
atg ccg caa atg aac act cag caa gtg aat taa tctgattcac aggattatgt 2228
Met Pro Gln Met Asn Thr Gln Gln Val Asn
700 705
ttaatcgcca aaaacacact ggccagtgta ccataatatg ttaccagaag agttattatc 2288
tatttgttct ccctttcagg aaacttattg taaagggact gttttcatcc cataaagaca 2348
ggactacaat tgtcagcttt atattacctg gatatggaag gaaactattt ttactctgca 2408
tgttctgtcc taagcgtcat cttgagcctt gcacatgata ctcagattcc tcacccttgc 2468
ttaggagtaa aacataatat actttaatgg ggtgatatct ccatagttat ttgaagtggc 2528
ttggataaag caagactgac ttctgacatt ggataaaatc tacaaatcag ccctagagtc 2588
attcagtggt aactgacaaa actaaaatat ttcccttgaa aggaagatgg aaggagtgga 2648
gtgtggtttg gcagaacaac tgcatttcac agcttttcca cttaaattgg agcactgaac 2708
atttagatgc ataccgaatt atgcatgggc cctaatcaca cagacaaggc tggtgccagc 2768
cttaggcttg acacggcagt gttcaccctc tggccagacg actgtggttc aagacacatg 2828
taaattgctt tttaacagct gatactgtat aagacaaagc caaaatgcaa aattaggctt 2888
tgattggcac ttttcgaaaa atatgcaaca attaagggat ataatctgga tggccgcttc 2948
tgtacttaat gtgaaatatt tagatacctt tcaaacactt aacagtttct ttgacaatga 3008
gttttgtaag gattggtagt aaatatcatt ccttatgacg tacattgtct gtcactaatc 3068
cttggatctt gctgtattgt cacctaaatt ggtacaggta ctgatgaaaa tctaatggat 3128
aatcataaca ctcttggtta catgtttttc ctgcagcctg aaagttttta taagaaaaag 3188
acatcaaatg cctgctgctg ccaccctttt aaattgctat cttttgaaaa gcaccagtat 3248
gtgttttaga ttgatttccc tattttaggg aaatgacagt cagtagtttc acttctgatg 3308
gtataagcaa acaaataaaa catgtttata aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 3368
aaaaaaaaaa aaaaaaaa 3386
<210> 16
<211> 708
<212> PRT
<213> 牛(Bos taurus)
<400> 16
Met Pro Ser Ala Thr Ser His Ser Gly Ser Gly Ser Lys Ser Ser Gly
1 5 10 15
Pro Pro Pro Pro Ser Gly Ser Ser Gly Asn Glu Ala Gly Ala Gly Ala
20 25 30
Ala Ala Pro Ala Ser Gln His Pro Met Thr Gly Thr Gly Ala Val Gln
35 40 45
Thr Glu Ala Met Lys Gln Ile Leu Gly Val Ile Asp Lys Lys Leu Arg
50 55 60
Asn Leu Glu Lys Lys Lys Gly Lys Leu Asp Asp Tyr Gln Glu Arg Met
65 70 75 80
Asn Lys Gly Glu Arg Leu Asn Gln Asp Gln Leu Asp Ala Val Ser Lys
85 90 95
Tyr Gln Glu Val Thr Asn Asn Leu Glu Phe Ala Lys Glu Leu Gln Arg
100 105 110
Ser Phe Met Ala Leu Ser Gln Asp Ile Gln Lys Thr Ile Lys Lys Thr
115 120 125
Ala Arg Arg Glu Gln Leu Met Arg Glu Glu Ala Glu Gln Lys Arg Leu
130 135 140
Lys Thr Val Leu Glu Leu Gln Tyr Val Leu Asp Lys Leu Gly Asp Asp
145 150 155 160
Glu Val Arg Thr Asp Leu Lys Gln Gly Leu Asn Gly Val Pro Ile Leu
165 170 175
Ser Glu Glu Glu Leu Ser Leu Leu Asp Glu Phe Tyr Lys Leu Ala Asp
180 185 190
Pro Glu Arg Asp Met Ser Leu Arg Leu Asn Glu Gln Tyr Glu His Ala
195 200 205
Ser Ile His Leu Trp Asp Leu Leu Glu Gly Lys Glu Lys Pro Val Cys
210 215 220
Gly Thr Thr Tyr Lys Ala Leu Lys Glu Ile Val Glu Arg Val Phe Gln
225 230 235 240
Ser Asn Tyr Phe Asp Ser Thr His Asn His Gln Asn Gly Leu Cys Glu
245 250 255
Glu Glu Glu Ala Ala Ser Ala Pro Thr Val Glu Asp Gln Ala Ala Glu
260 265 270
Ala Glu Pro Glu Pro Val Glu Glu Tyr Thr Glu Gln Asn Glu Val Glu
275 280 285
Ser Thr Glu Tyr Val Asn Arg Gln Phe Met Ala Glu Thr Gln Phe Ser
290 295 300
Ser Gly Glu Lys Glu Gln Val Asp Asp Trp Thr Val Glu Thr Val Glu
305 310 315 320
Val Val Asn Ser Leu Gln Gln Gln Pro Gln Ala Ala Ser Pro Ser Val
325 330 335
Pro Glu Pro His Ser Leu Thr Pro Val Ala Gln Ala Asp Pro Leu Val
340 345 350
Arg Arg Gln Arg Val Gln Asp Leu Met Ala Gln Met Gln Gly Pro Tyr
355 360 365
Asn Phe Ile Gln Asp Ser Met Leu Asp Phe Glu Asn Gln Thr Leu Asp
370 375 380
Pro Ala Ile Val Ser Ala Gln Pro Met Asn Pro Ala Gln Asn Met Asp
385 390 395 400
Ile Pro Gln Leu Val Cys Pro Pro Val His Ser Glu Ser Arg Leu Ala
405 410 415
Gln Pro Asn Gln Val Ser Val Gln Pro Glu Ala Thr Gln Val Pro Leu
420 425 430
Val Ser Ser Thr Ser Glu Gly Tyr Thr Ala Ser Gln Pro Leu Tyr Gln
435 440 445
Pro Ser His Ala Thr Asp Gln Arg Pro Gln Lys Glu Pro Ile Asp Gln
450 455 460
Ile Gln Ala Thr Ile Ser Leu Asn Thr Asp Gln Thr Thr Ala Ser Ser
465 470 475 480
Ser Leu Pro Ala Ala Ser Gln Pro Gln Val Phe Gln Ala Gly Thr Ser
485 490 495
Lys Pro Leu His Ser Ser Gly Ile Asn Val Asn Ala Ala Pro Phe Gln
500 505 510
Ser Met Gln Thr Val Phe Asn Met Asn Ala Pro Val Pro Pro Val Asn
515 520 525
Glu Pro Glu Thr Leu Lys Gln Gln Asn Gln Tyr Gln Ala Ser Tyr Asn
530 535 540
Gln Ser Phe Ser Ser Gln Pro His Gln Val Glu Gln Thr Glu Leu Gln
545 550 555 560
Gln Glu Gln Leu Gln Thr Val Val Gly Thr Tyr His Gly Ser Gln Asp
565 570 575
Gln Pro His Gln Val Thr Gly Asn His Gln Gln Pro Pro Gln Gln Asn
580 585 590
Thr Gly Phe Pro Arg Ser Asn Gln Pro Tyr Tyr Asn Ser Arg Gly Val
595 600 605
Ser Arg Gly Gly Ser Arg Gly Ala Arg Gly Leu Met Asn Gly Tyr Arg
610 615 620
Gly Pro Ala Asn Gly Phe Arg Gly Gly Tyr Asp Gly Tyr Arg Pro Ser
625 630 635 640
Phe Ser Thr Asn Thr Pro Asn Ser Gly Tyr Thr Gln Ser Gln Phe Ser
645 650 655
Ala Pro Arg Asp Tyr Ser Gly Tyr Gln Arg Asp Gly Tyr Gln Gln Asn
660 665 670
Phe Lys Arg Gly Ser Gly Gln Ser Gly Pro Arg Gly Ala Pro Arg Gly
675 680 685
Arg Gly Gly Pro Pro Arg Pro Asn Arg Gly Met Pro Gln Met Asn Thr
690 695 700
Gln Gln Val Asn
705
<210> 17
<211> 3150
<212> DNA
<213> 马(Equus caballus)
<220>
<221> CDS
<222> (1)..(1917)
<400> 17
atg gag ggc aag ctc gat gat tac caa gag cga atg aac aaa gga gaa 48
Met Glu Gly Lys Leu Asp Asp Tyr Gln Glu Arg Met Asn Lys Gly Glu
1 5 10 15
agg ctt aat cag gat cag ctg gat gct gtg tct aag tac cag gaa gtc 96
Arg Leu Asn Gln Asp Gln Leu Asp Ala Val Ser Lys Tyr Gln Glu Val
20 25 30
aca aat aac ttg gag ttt gcg aaa gaa ttg cag agg agt ttc atg gcg 144
Thr Asn Asn Leu Glu Phe Ala Lys Glu Leu Gln Arg Ser Phe Met Ala
35 40 45
ttg agt cag gat att cag aaa aca ata aag aag acg gca cgt cgg gag 192
Leu Ser Gln Asp Ile Gln Lys Thr Ile Lys Lys Thr Ala Arg Arg Glu
50 55 60
cag ctt atg aga gaa gaa gct gaa cag aaa cgt tta aaa act gta ctt 240
Gln Leu Met Arg Glu Glu Ala Glu Gln Lys Arg Leu Lys Thr Val Leu
65 70 75 80
gag ctg cag tat gtt ttg gac aaa ttg gga gat gaa gaa gtg cga act 288
Glu Leu Gln Tyr Val Leu Asp Lys Leu Gly Asp Glu Glu Val Arg Thr
85 90 95
gac ctg aaa caa ggt ttg aat gga gtg cca ata ctc tct gaa gaa gag 336
Asp Leu Lys Gln Gly Leu Asn Gly Val Pro Ile Leu Ser Glu Glu Glu
100 105 110
ttg tcg ctg ttg gat gag ttc tac aag tta gca gac cct gta cgg gac 384
Leu Ser Leu Leu Asp Glu Phe Tyr Lys Leu Ala Asp Pro Val Arg Asp
115 120 125
atg agc ttg agg ttg aat gag cag tat gag cat gcc tcc att cac ctg 432
Met Ser Leu Arg Leu Asn Glu Gln Tyr Glu His Ala Ser Ile His Leu
130 135 140
tgg gac ttg ctg gaa ggg aag gaa aaa tct gtc tgt gga aca acc tat 480
Trp Asp Leu Leu Glu Gly Lys Glu Lys Ser Val Cys Gly Thr Thr Tyr
145 150 155 160
aaa gct ctg agg gaa att gtt gag cgt gtt ttc cag tcc aac tac ttt 528
Lys Ala Leu Arg Glu Ile Val Glu Arg Val Phe Gln Ser Asn Tyr Phe
165 170 175
gac agc acc cac aac cac cag aat ggg ctc tgt gag gag gaa gag gct 576
Asp Ser Thr His Asn His Gln Asn Gly Leu Cys Glu Glu Glu Glu Ala
180 185 190
acc tca gct cca aca gct gaa gac cag gga gct gaa gct gaa cct gag 624
Thr Ser Ala Pro Thr Ala Glu Asp Gln Gly Ala Glu Ala Glu Pro Glu
195 200 205
cca gca gaa gaa tac act gaa caa agt gaa gtt gaa tca aca gag tat 672
Pro Ala Glu Glu Tyr Thr Glu Gln Ser Glu Val Glu Ser Thr Glu Tyr
210 215 220
gta aat aga cag ttt atg gca gaa gcg cag ttc agt ggt gag aag gag 720
Val Asn Arg Gln Phe Met Ala Glu Ala Gln Phe Ser Gly Glu Lys Glu
225 230 235 240
cag gtg gat gag tgg aca gtc gag acg gtc gag gtg gta aat tca ctc 768
Gln Val Asp Glu Trp Thr Val Glu Thr Val Glu Val Val Asn Ser Leu
245 250 255
cag cag caa cct cag gct gca tct cct tca gta ccg gag ccc cac tct 816
Gln Gln Gln Pro Gln Ala Ala Ser Pro Ser Val Pro Glu Pro His Ser
260 265 270
ttg act cca gtg gct cag gca gat ccc ctt gtg aga aga cag cga gta 864
Leu Thr Pro Val Ala Gln Ala Asp Pro Leu Val Arg Arg Gln Arg Val
275 280 285
cag gac ctt atg gcg caa atg cag ggg ccc tat aat ttc ata cag gat 912
Gln Asp Leu Met Ala Gln Met Gln Gly Pro Tyr Asn Phe Ile Gln Asp
290 295 300
tca atg ctg gat ttt gaa aac cag aca ctt gat cct gcc att gta tct 960
Ser Met Leu Asp Phe Glu Asn Gln Thr Leu Asp Pro Ala Ile Val Ser
305 310 315 320
gca cag cct atg aat cca gca cag aat atg gac atg ccc cag ctg gtt 1008
Ala Gln Pro Met Asn Pro Ala Gln Asn Met Asp Met Pro Gln Leu Val
325 330 335
tgc cct cca gtt cat gct gaa tct aga ctt gct caa cct aat caa gtt 1056
Cys Pro Pro Val His Ala Glu Ser Arg Leu Ala Gln Pro Asn Gln Val
340 345 350
cct gta caa cca gaa gct aca cag gtt cct ttg gtt tca tcc aca agt 1104
Pro Val Gln Pro Glu Ala Thr Gln Val Pro Leu Val Ser Ser Thr Ser
355 360 365
gag ggg tat aca gca tct cag ccc ttg tac cag cct tct cat gct aca 1152
Glu Gly Tyr Thr Ala Ser Gln Pro Leu Tyr Gln Pro Ser His Ala Thr
370 375 380
gag caa cga ccg caa aag gaa ccg act gac cag atc cag gca aca atc 1200
Glu Gln Arg Pro Gln Lys Glu Pro Thr Asp Gln Ile Gln Ala Thr Ile
385 390 395 400
tct tta aat aca gac cag act aca gca tca tca tcc ctt cct gct gct 1248
Ser Leu Asn Thr Asp Gln Thr Thr Ala Ser Ser Ser Leu Pro Ala Ala
405 410 415
tct cag cct cag gtg ttc cag gct ggg aca agc aaa cct tta cac agc 1296
Ser Gln Pro Gln Val Phe Gln Ala Gly Thr Ser Lys Pro Leu His Ser
420 425 430
agt ggg atc aat gta aat gca gcg cca ttc cag tcc atg caa acg gtg 1344
Ser Gly Ile Asn Val Asn Ala Ala Pro Phe Gln Ser Met Gln Thr Val
435 440 445
ttc aac atg aat gcc ccg gtt cct cct gtt aat gaa cca gaa act tta 1392
Phe Asn Met Asn Ala Pro Val Pro Pro Val Asn Glu Pro Glu Thr Leu
450 455 460
aaa cag caa aat cag tac cag gcc agc tat aac cag agc ttt tcc agt 1440
Lys Gln Gln Asn Gln Tyr Gln Ala Ser Tyr Asn Gln Ser Phe Ser Ser
465 470 475 480
ccg cct cac caa gta gag cag aca gag ctt ccg caa gag cag ctt cag 1488
Pro Pro His Gln Val Glu Gln Thr Glu Leu Pro Gln Glu Gln Leu Gln
485 490 495
acg gtg gtt ggt act tac cat gct tcc caa gac cag ccc cat caa gtg 1536
Thr Val Val Gly Thr Tyr His Ala Ser Gln Asp Gln Pro His Gln Val
500 505 510
acc ggt aac cac cag cag cct ccc cag cag aac act ggg ttt cca cgt 1584
Thr Gly Asn His Gln Gln Pro Pro Gln Gln Asn Thr Gly Phe Pro Arg
515 520 525
agc agt cag ccc tat tac aac agt cgt ggt gtg tct cgt gga ggc tcc 1632
Ser Ser Gln Pro Tyr Tyr Asn Ser Arg Gly Val Ser Arg Gly Gly Ser
530 535 540
cgt ggt gct aga ggc ttg atg aat gga tac agg ggc cct gcc aat gga 1680
Arg Gly Ala Arg Gly Leu Met Asn Gly Tyr Arg Gly Pro Ala Asn Gly
545 550 555 560
ttc aga gga gga tat gat ggt tac cgc cct tcg ttc tct aac act cca 1728
Phe Arg Gly Gly Tyr Asp Gly Tyr Arg Pro Ser Phe Ser Asn Thr Pro
565 570 575
aac agc ggt tac aca cag tct cag ttc agt gct ccc cgg gac tac tct 1776
Asn Ser Gly Tyr Thr Gln Ser Gln Phe Ser Ala Pro Arg Asp Tyr Ser
580 585 590
ggc tat cag cgg gat gga tat cag cag aat ttc aag cga ggc tct ggg 1824
Gly Tyr Gln Arg Asp Gly Tyr Gln Gln Asn Phe Lys Arg Gly Ser Gly
595 600 605
cag agt gga ccc cgg gga gcc cca cga ggt cgt gga ggg ccc cca aga 1872
Gln Ser Gly Pro Arg Gly Ala Pro Arg Gly Arg Gly Gly Pro Pro Arg
610 615 620
ccc aac aga ggg atg ccg caa atg aac act cag caa gtg aat taa 1917
Pro Asn Arg Gly Met Pro Gln Met Asn Thr Gln Gln Val Asn
625 630 635
tctgattcac aggattatct ttaatcgcca aaacacactg gccagtgtac cataatatgt 1977
taccagaaga gttattatct atttgttctc cctttcagga aacttattgt aaagggactg 2037
ttttcatccc ataaagacag gactacagtt gtcagcttta tattacctgg atatggaagg 2097
aaactatttt tactctgcat gttctgtcct aagcgtcatc ttgagccttg cacatgatac 2157
tcagattcct ttcccttgct taggagtaaa acataatata ctttatgggg tgataatatc 2217
tccatagtta tttgaagtgg cttggaaaaa gcaagattga cttttgacat tggataaaat 2277
ctacaaatca gccctagagt ttcatggtca ttcacaaaac taaaatattt cccttgaaag 2337
gaagatggaa ggactggagt gtggtttggc agaacaactg catttcacag cttttcctat 2397
taaattggag cactgaatgt taaatgcata ccaaattatg catgggccct taatcacaca 2457
tacatggcta ccagctttga cacagcacta ttcatcctct ggccaaacga ctgtggttaa 2517
aaacacgtgt aaattgcttt ttaacagctg atactgtaaa agacaaagct aaaatgcaaa 2577
attaggcttt cattggcact tttcgaaaaa tatgcaacaa atttgggatg taatctggat 2637
ggccacttct gtacttaatg tgaagtattt agataccttt ttgaacactt aacagtttct 2697
tcgacaatga cttttgtaag gattggtagt atatatcatt ccttatgaca tacattgtct 2757
gttgctaatc cttggatctt gctgtattgt cacctaaatt ggtacaggta ctgatgaaaa 2817
tctctcatgg ataaacctaa cactcttcgt cacatgtttt tcctgcagcc tgaaggtttt 2877
taaaaggaaa agatatcaaa tgcctgctgc taccaccctt ttaaattgct atcttttgaa 2937
aagcaccagt atgtgttttt agattgattt ccctatttta gggaaatgac agtcagtagt 2997
ttcagttctg atggtataag caaagcaaat aaaacgtgtt tataaaagtt gtatcttgaa 3057
acactggtgt tcaacagcta gcagcttctg tggttcaccc cctgccttgt tagtgttacc 3117
catttatggt tatctccagc agcaatttct cta 3150
<210> 18
<211> 638
<212> PRT
<213> 马(Equus caballus)
<400> 18
Met Glu Gly Lys Leu Asp Asp Tyr Gln Glu Arg Met Asn Lys Gly Glu
1 5 10 15
Arg Leu Asn Gln Asp Gln Leu Asp Ala Val Ser Lys Tyr Gln Glu Val
20 25 30
Thr Asn Asn Leu Glu Phe Ala Lys Glu Leu Gln Arg Ser Phe Met Ala
35 40 45
Leu Ser Gln Asp Ile Gln Lys Thr Ile Lys Lys Thr Ala Arg Arg Glu
50 55 60
Gln Leu Met Arg Glu Glu Ala Glu Gln Lys Arg Leu Lys Thr Val Leu
65 70 75 80
Glu Leu Gln Tyr Val Leu Asp Lys Leu Gly Asp Glu Glu Val Arg Thr
85 90 95
Asp Leu Lys Gln Gly Leu Asn Gly Val Pro Ile Leu Ser Glu Glu Glu
100 105 110
Leu Ser Leu Leu Asp Glu Phe Tyr Lys Leu Ala Asp Pro Val Arg Asp
115 120 125
Met Ser Leu Arg Leu Asn Glu Gln Tyr Glu His Ala Ser Ile His Leu
130 135 140
Trp Asp Leu Leu Glu Gly Lys Glu Lys Ser Val Cys Gly Thr Thr Tyr
145 150 155 160
Lys Ala Leu Arg Glu Ile Val Glu Arg Val Phe Gln Ser Asn Tyr Phe
165 170 175
Asp Ser Thr His Asn His Gln Asn Gly Leu Cys Glu Glu Glu Glu Ala
180 185 190
Thr Ser Ala Pro Thr Ala Glu Asp Gln Gly Ala Glu Ala Glu Pro Glu
195 200 205
Pro Ala Glu Glu Tyr Thr Glu Gln Ser Glu Val Glu Ser Thr Glu Tyr
210 215 220
Val Asn Arg Gln Phe Met Ala Glu Ala Gln Phe Ser Gly Glu Lys Glu
225 230 235 240
Gln Val Asp Glu Trp Thr Val Glu Thr Val Glu Val Val Asn Ser Leu
245 250 255
Gln Gln Gln Pro Gln Ala Ala Ser Pro Ser Val Pro Glu Pro His Ser
260 265 270
Leu Thr Pro Val Ala Gln Ala Asp Pro Leu Val Arg Arg Gln Arg Val
275 280 285
Gln Asp Leu Met Ala Gln Met Gln Gly Pro Tyr Asn Phe Ile Gln Asp
290 295 300
Ser Met Leu Asp Phe Glu Asn Gln Thr Leu Asp Pro Ala Ile Val Ser
305 310 315 320
Ala Gln Pro Met Asn Pro Ala Gln Asn Met Asp Met Pro Gln Leu Val
325 330 335
Cys Pro Pro Val His Ala Glu Ser Arg Leu Ala Gln Pro Asn Gln Val
340 345 350
Pro Val Gln Pro Glu Ala Thr Gln Val Pro Leu Val Ser Ser Thr Ser
355 360 365
Glu Gly Tyr Thr Ala Ser Gln Pro Leu Tyr Gln Pro Ser His Ala Thr
370 375 380
Glu Gln Arg Pro Gln Lys Glu Pro Thr Asp Gln Ile Gln Ala Thr Ile
385 390 395 400
Ser Leu Asn Thr Asp Gln Thr Thr Ala Ser Ser Ser Leu Pro Ala Ala
405 410 415
Ser Gln Pro Gln Val Phe Gln Ala Gly Thr Ser Lys Pro Leu His Ser
420 425 430
Ser Gly Ile Asn Val Asn Ala Ala Pro Phe Gln Ser Met Gln Thr Val
435 440 445
Phe Asn Met Asn Ala Pro Val Pro Pro Val Asn Glu Pro Glu Thr Leu
450 455 460
Lys Gln Gln Asn Gln Tyr Gln Ala Ser Tyr Asn Gln Ser Phe Ser Ser
465 470 475 480
Pro Pro His Gln Val Glu Gln Thr Glu Leu Pro Gln Glu Gln Leu Gln
485 490 495
Thr Val Val Gly Thr Tyr His Ala Ser Gln Asp Gln Pro His Gln Val
500 505 510
Thr Gly Asn His Gln Gln Pro Pro Gln Gln Asn Thr Gly Phe Pro Arg
515 520 525
Ser Ser Gln Pro Tyr Tyr Asn Ser Arg Gly Val Ser Arg Gly Gly Ser
530 535 540
Arg Gly Ala Arg Gly Leu Met Asn Gly Tyr Arg Gly Pro Ala Asn Gly
545 550 555 560
Phe Arg Gly Gly Tyr Asp Gly Tyr Arg Pro Ser Phe Ser Asn Thr Pro
565 570 575
Asn Ser Gly Tyr Thr Gln Ser Gln Phe Ser Ala Pro Arg Asp Tyr Ser
580 585 590
Gly Tyr Gln Arg Asp Gly Tyr Gln Gln Asn Phe Lys Arg Gly Ser Gly
595 600 605
Gln Ser Gly Pro Arg Gly Ala Pro Arg Gly Arg Gly Gly Pro Pro Arg
610 615 620
Pro Asn Arg Gly Met Pro Gln Met Asn Thr Gln Gln Val Asn
625 630 635
<210> 19
<211> 6181
<212> DNA
<213> 小鼠(Mus musculus)
<220>
<221> CDS
<222> (179)..(2302)
<400> 19
gctggctggc taagtccctc ccgcgccggc tcttgtccca ctaggagcag ctcagagccg 60
cggggacagg gcgaagcggc ctgcgcccac ggagcgcacg tctctgttct caacgcagca 120
ccacccttgc ccccctcggc tgcccactcc agacgtccag cggctccgcg cgcgcacg 178
atg ccc tcg gcc acc agc cac agc gga agc ggc agc aaa tcg tcg gga 226
Met Pro Ser Ala Thr Ser His Ser Gly Ser Gly Ser Lys Ser Ser Gly
1 5 10 15
ccg ccg ccg ccg tcc ggt tcc tcc ggg agt gag gcg gcg gcc ggg gca 274
Pro Pro Pro Pro Ser Gly Ser Ser Gly Ser Glu Ala Ala Ala Gly Ala
20 25 30
gct gcg ccg gct tct cag cat ccg gca acc ggc acc ggc gcc gtc cag 322
Ala Ala Pro Ala Ser Gln His Pro Ala Thr Gly Thr Gly Ala Val Gln
35 40 45
acc gag gcc atg aag cag att ctc ggc gta atc gac aag aaa ctt cgg 370
Thr Glu Ala Met Lys Gln Ile Leu Gly Val Ile Asp Lys Lys Leu Arg
50 55 60
aac ctg gag aag aaa aag ggt aaa ctt gat gat tac cag gaa cga atg 418
Asn Leu Glu Lys Lys Lys Gly Lys Leu Asp Asp Tyr Gln Glu Arg Met
65 70 75 80
aat aaa ggg gaa agg ctc aat caa gac cag ctg gat gcc gta tct aag 466
Asn Lys Gly Glu Arg Leu Asn Gln Asp Gln Leu Asp Ala Val Ser Lys
85 90 95
tac cag gaa gtc aca aat aat ttg gag ttt gca aag gaa tta cag agg 514
Tyr Gln Glu Val Thr Asn Asn Leu Glu Phe Ala Lys Glu Leu Gln Arg
100 105 110
agt ttc atg gca tta agt caa gat att cag aaa aca ata aag aag aca 562
Ser Phe Met Ala Leu Ser Gln Asp Ile Gln Lys Thr Ile Lys Lys Thr
115 120 125
gca cgt cgg gaa cag ctt atg aga gaa gaa gca gaa cag aag cgc tta 610
Ala Arg Arg Glu Gln Leu Met Arg Glu Glu Ala Glu Gln Lys Arg Leu
130 135 140
aaa act gta ctt gag tta cag tat gta ttg gat aag ctg gga gat gat 658
Lys Thr Val Leu Glu Leu Gln Tyr Val Leu Asp Lys Leu Gly Asp Asp
145 150 155 160
gat gtg aga aca gat ctg aaa caa ggt ttg agt gga gtg cca ata ttg 706
Asp Val Arg Thr Asp Leu Lys Gln Gly Leu Ser Gly Val Pro Ile Leu
165 170 175
tct gag gag gag ttg tca ttg ctg gat gag ttc tac aag ctc gta gat 754
Ser Glu Glu Glu Leu Ser Leu Leu Asp Glu Phe Tyr Lys Leu Val Asp
180 185 190
cct gag cgt gac atg agt tta agg tta aat gag cag tat gaa cat gcc 802
Pro Glu Arg Asp Met Ser Leu Arg Leu Asn Glu Gln Tyr Glu His Ala
195 200 205
tca att cac ttg tgg gat ttg ctg gaa ggg aaa gaa aag cct gtg tgt 850
Ser Ile His Leu Trp Asp Leu Leu Glu Gly Lys Glu Lys Pro Val Cys
210 215 220
gga aca acc tat aaa gct cta aag gaa att gtt gag cgt gtt ttc cag 898
Gly Thr Thr Tyr Lys Ala Leu Lys Glu Ile Val Glu Arg Val Phe Gln
225 230 235 240
tca aac tac ttt gat agc act cac aat cat caa aat ggg ttg tgt gag 946
Ser Asn Tyr Phe Asp Ser Thr His Asn His Gln Asn Gly Leu Cys Glu
245 250 255
gag gaa gag gcg gct tca gcg ccc aca gtg gag gac cag gta gct gaa 994
Glu Glu Glu Ala Ala Ser Ala Pro Thr Val Glu Asp Gln Val Ala Glu
260 265 270
gct gaa cct gag cca gcg gaa gaa tac aca gag caa agt gag gtt gaa 1042
Ala Glu Pro Glu Pro Ala Glu Glu Tyr Thr Glu Gln Ser Glu Val Glu
275 280 285
tca aca gag tat gtc aat agg cag ttc atg gca gaa aca cag ttc agc 1090
Ser Thr Glu Tyr Val Asn Arg Gln Phe Met Ala Glu Thr Gln Phe Ser
290 295 300
agt ggt gag aag gag caa gtg gat gag tgg aca gtt gaa aca gtt gag 1138
Ser Gly Glu Lys Glu Gln Val Asp Glu Trp Thr Val Glu Thr Val Glu
305 310 315 320
gtt gta aac tca ctc cag cag caa cct cag gct gcg tcc cct tca gtc 1186
Val Val Asn Ser Leu Gln Gln Gln Pro Gln Ala Ala Ser Pro Ser Val
325 330 335
cca gag ccc cac tct ttg act cca gtg gct cag tca gat cca ctt gtg 1234
Pro Glu Pro His Ser Leu Thr Pro Val Ala Gln Ser Asp Pro Leu Val
340 345 350
aga agg cag cgt gta caa gat ctt atg gca caa atg caa ggg ccc tat 1282
Arg Arg Gln Arg Val Gln Asp Leu Met Ala Gln Met Gln Gly Pro Tyr
355 360 365
aat ttc ata cag gat tca atg ttg gat ttt gaa aat cag acg ctt gat 1330
Asn Phe Ile Gln Asp Ser Met Leu Asp Phe Glu Asn Gln Thr Leu Asp
370 375 380
cct gcc att gta tcc gca cag cct atg aac cct acc cag aac atg gat 1378
Pro Ala Ile Val Ser Ala Gln Pro Met Asn Pro Thr Gln Asn Met Asp
385 390 395 400
atg cct cag ctg gtt tgc cct cag gtt cat tct gaa tct aga ctt gcc 1426
Met Pro Gln Leu Val Cys Pro Gln Val His Ser Glu Ser Arg Leu Ala
405 410 415
caa tct aat caa gtt cct gta caa cca gaa gcc aca cag gtt cct ttg 1474
Gln Ser Asn Gln Val Pro Val Gln Pro Glu Ala Thr Gln Val Pro Leu
420 425 430
gtt tca tcc aca agt gag ggg tat aca gca tct cag ccc ttg tac cag 1522
Val Ser Ser Thr Ser Glu Gly Tyr Thr Ala Ser Gln Pro Leu Tyr Gln
435 440 445
cca tct cat gct acg gag cag cgg ccg cag aaa gag cca atg gat cag 1570
Pro Ser His Ala Thr Glu Gln Arg Pro Gln Lys Glu Pro Met Asp Gln
450 455 460
att cag gca aca ata tct ttg aat aca gac cag act aca gca tcc tca 1618
Ile Gln Ala Thr Ile Ser Leu Asn Thr Asp Gln Thr Thr Ala Ser Ser
465 470 475 480
tcc ctt cct gct gct tct cag cct caa gtg ttc cag gct ggg aca agt 1666
Ser Leu Pro Ala Ala Ser Gln Pro Gln Val Phe Gln Ala Gly Thr Ser
485 490 495
aaa cct ttg cac agc agt gga atc aat gta aat gca gct cca ttc cag 1714
Lys Pro Leu His Ser Ser Gly Ile Asn Val Asn Ala Ala Pro Phe Gln
500 505 510
tcc atg caa acg gtg ttc aat atg aat gct cca gtc cct cct gct aat 1762
Ser Met Gln Thr Val Phe Asn Met Asn Ala Pro Val Pro Pro Ala Asn
515 520 525
gaa cca gaa acg tta aaa caa cag agt cag tac cag gcc act tat aac 1810
Glu Pro Glu Thr Leu Lys Gln Gln Ser Gln Tyr Gln Ala Thr Tyr Asn
530 535 540
cag agt ttt tcc agt cag cct cac caa gtg gaa caa aca gag ctt caa 1858
Gln Ser Phe Ser Ser Gln Pro His Gln Val Glu Gln Thr Glu Leu Gln
545 550 555 560
caa gac caa ctg caa acg gtg gtt ggc act tac cat gga tcc cag gac 1906
Gln Asp Gln Leu Gln Thr Val Val Gly Thr Tyr His Gly Ser Gln Asp
565 570 575
cag cct cat caa gtg cct ggt aac cac cag caa ccc cca cag cag aac 1954
Gln Pro His Gln Val Pro Gly Asn His Gln Gln Pro Pro Gln Gln Asn
580 585 590
act ggc ttt cca cgt agc agt cag cct tat tac aac agt cgt ggg gta 2002
Thr Gly Phe Pro Arg Ser Ser Gln Pro Tyr Tyr Asn Ser Arg Gly Val
595 600 605
tct cga gga ggg tct cgt ggt gcc aga ggc ttg atg aat gga tac agg 2050
Ser Arg Gly Gly Ser Arg Gly Ala Arg Gly Leu Met Asn Gly Tyr Arg
610 615 620
ggc cct gcc aat gga ttt aga gga gga tat gat ggt tac cgc cct tca 2098
Gly Pro Ala Asn Gly Phe Arg Gly Gly Tyr Asp Gly Tyr Arg Pro Ser
625 630 635 640
ttc tcg aac act cca aac agt ggt tat tca cag tct cag ttc act gct 2146
Phe Ser Asn Thr Pro Asn Ser Gly Tyr Ser Gln Ser Gln Phe Thr Ala
645 650 655
ccc cgg gac tac tct ggt tac cag cgg gat gga tat cag cag aat ttc 2194
Pro Arg Asp Tyr Ser Gly Tyr Gln Arg Asp Gly Tyr Gln Gln Asn Phe
660 665 670
aag cga ggc tct ggg cag agt gga cca cgg gga gcc cca cga ggt cgt 2242
Lys Arg Gly Ser Gly Gln Ser Gly Pro Arg Gly Ala Pro Arg Gly Arg
675 680 685
gga ggg ccc cca aga ccc aac aga ggg atg ccg caa atg aac act cag 2290
Gly Gly Pro Pro Arg Pro Asn Arg Gly Met Pro Gln Met Asn Thr Gln
690 695 700
caa gtg aat taa tgtgatacac aggattatgt ttaatcgcca aaaacacact 2342
Gln Val Asn
705
ggccagtgta ccataatatg ttaccagaag agttattatc tatttgttct ccctttcagg 2402
aaacttattg taaagggact gttttcatcc cataaagaca ggactgcaat tgtcagcttt 2462
acattacctg gatatggaag gaaactattt ttattctgca tgttctgtcc taagcgtcat 2522
cttgagcctt gcacacaata caatactcag attcctcacc cttgcttagg agtaaaacat 2582
tatatactta tggggtgata atatctccat agttagttga agtggcttgg aaaaaaaatg 2642
caagattgaa tttttgacct tggataaaat ctacaatcag ccctagaact attcagtggt 2702
aattgacaaa gttaaagcat tttctttgaa aggaagatgg aaggagtgga gtgtggttta 2762
gcaaaactgc atttcatagc tttcccatta aattggagca ccgacagatt aaaagcatac 2822
caaattatgc atgggtcctt actcacacaa gtgaggctgg ctaccagcct tgacatagca 2882
ctcactagtc ttctggccaa acgactgtga ttaaaacaca tgtaaattgc tctttagtag 2942
tggatactgt gtaagacaaa gccaaattgc aaatcaggct ttgattggct cttctggaaa 3002
atatgcatca aatatggggg ataatctgga tgggctgctg ctgtgctcaa tgtgaactat 3062
ttagatacct ttggaacact taacagtttc tctgaacaat gacttacatg gggattggtc 3122
ctgtttgtca ttcctcacca taattgcatt gtcatcacta atccttggat cttgctgtat 3182
tgttactcaa attggtaata ggtactgatg gaaatcgcta atggatggat aatcataaca 3242
cttttggtca catgttttct cctgcagcct gaaagttctt aaagaaaaag atatcaaatg 3302
cctgctgcta ccaccctttt aaattgctat ctttagaaaa gcaccggtat gtgttttaga 3362
ttcatttccc tgttttaggg aaatgacagg cagtagtttc agttctgatg gcaaaacaaa 3422
taaaaacatg tttctaaaag ttgtatcttg aaacactggt gttcaacagc tagcagctaa 3482
agtaattcaa cccatgcatt gctagtgtca cagcctttgg ttatgtctag tagctgtttc 3542
tgaagtattt tcatttatct tttgtcaaat ttaaccctgt ttgaattctc tcctttcctc 3602
aaggagacac ttatgttcaa agtgttgatt ctttgcctta ggtgcataga gagtagacag 3662
tttggagatg gaaaggttag cagtgactta gccatatgtt ctgtgttgga atttgtgcta 3722
gcagtttgag cactagctct gcgtgcctat gaactgaatg ctgcttgtcc cattccattt 3782
tatgtcatgg agaaataatt ccacttggta acacaaaggc taagttaatg ttattttctg 3842
tacagaaatt aaattttact tttagccttt tgtaaacttt tttttttttt ttccaagccg 3902
gtatcagcta ctcaaaacaa ttctcagata ttcatcatta gacaactgga gtttttgctg 3962
gttttgtagc ctactaaaac tgctgaggct gttgaacatt ccacattcaa aagttttgta 4022
gggtggtgga taatggggaa gcttcaatgt ttattttaaa ataaataaaa taagttcttg 4082
acttttctca tgtgtggtta tggtacatca tattggaagg gttatctgtt tacttttgcc 4142
aagactattt tgccagcacc tacacttgtg tgctttaaaa gacaactacc tgggatgtac 4202
cacaaccata tgttaattgt attttattgg gatggataaa atgtttgtgg tttattggat 4262
aatccctaga tggtgtgtta cgtgtgtaga atataatttt atgatagtaa gaaagcaaaa 4322
ttgaagaaaa taagtttagt attgaatttg agttctgaag tgaattcagg gaatgtctca 4382
cgtttcgggc ttctacccaa agtgtagggc agaaggtgta aaagttgttt gtagtttgac 4442
ttgtttattt tttaagttgc ttattccttt caacagcaac atatcattag ctgtcattct 4502
accattgcag ttctagtgag ttttaacgtc tgcattcaag actgttttaa aagcaacctc 4562
actggacaga gaactgctaa agtcttttcc ttaagatctg agtctttgtt actcagtatc 4622
ttctataata tgcaaatgct tgtctagagg cagaagacct tttgtttggt caagtgtgta 4682
ttttaccaga gtacagggaa ctgatggtcc tacatgtctc ttagtgtagt aagactataa 4742
aatcttttgt acatgcacaa ttcacagtat gtttagatac cacgtgtata atgccccccc 4802
ctcccccagg tagcatgcca ttgatgactt tttgcttagg gccattttat taccagggcc 4862
ttaatattcc taaaaagatg attttttttc atcctttctc ctcttttgat cattgtatct 4922
tgatattaaa aacatgacct tccaatgatt gtagtaaatt aacttctata gttcttttgt 4982
ctctatatgt attcatatat atgctattgt atagagactt caaggagaca tggagatgca 5042
tgcttattct caggttcatt cactaaggtg cttggcagac aaccagtttc taagtgcaga 5102
atgtagttaa gcagcttcat atatgtgcca ggcaatttgt tttgttaaat tttcatctac 5162
ttaaggaaat agggtattgt agcttaggct gatcataccc ttcatttcaa ccttaagctc 5222
tcaacctgca tccatccgac ttgagctatt aagtacttta gttttatcga gtataagtta 5282
acagaaaaag taaattaagc tttgccttta ctattttgaa tttatataca ttctggaaaa 5342
acttagaaac tgttgtatat ttcattagat taaattatat gaaaatgtga ttgtttatag 5402
caaagcctgt gagttgcata caccctaagg aaaactcctt aagtgctcct tgaagagaga 5462
agaaacaatt ctgggtctgg tctttttaag aacaaagcta gactactgta tgttagcact 5522
gtacattaat agtctgttgt gaagcttgag cagtttcctg catagccttg atccttcacc 5582
gttggcattg aaaatagcag tatccctgat gtacttaaaa cttaaagtca ggttttggta 5642
tatttatttg taagtcttaa tttcctctaa atactatatc tctttagcga gacaacctga 5702
aatttattag cacatttggg tatctcttgc ttggcattat ggccagtgtt aactattcag 5762
tggtgaaaaa attacccctc aagacactgg agtgacccca gatgtgtgta gtaagtggca 5822
tggttcaact gtgtggttaa tgataaatat atgacttagt cggtatgatc tggaaagact 5882
tgattgaaag ataattcagc tgacataagg atgagtgagg agtggcaaac tggataaaag 5942
agtcaagaga cctgtattcc agtgactcct gttttgttta agcattagca agatctgtct 6002
ggggaaactg gatagggcag ttttcttcca tgtttagttt ttgtctcaac atttggaagc 6062
tattgaaggt tttaaaatgg tgtgtattgt ttttttttgg ggggggggtg gccagaatag 6122
tgggtcatct aataaaactg ccatttaaaa gatcaaaaaa aaaaaaaaaa aaaaaaaaa 6181
<210> 20
<211> 707
<212> PRT
<213> 小鼠(Mus musculus)
<400> 20
Met Pro Ser Ala Thr Ser His Ser Gly Ser Gly Ser Lys Ser Ser Gly
1 5 10 15
Pro Pro Pro Pro Ser Gly Ser Ser Gly Ser Glu Ala Ala Ala Gly Ala
20 25 30
Ala Ala Pro Ala Ser Gln His Pro Ala Thr Gly Thr Gly Ala Val Gln
35 40 45
Thr Glu Ala Met Lys Gln Ile Leu Gly Val Ile Asp Lys Lys Leu Arg
50 55 60
Asn Leu Glu Lys Lys Lys Gly Lys Leu Asp Asp Tyr Gln Glu Arg Met
65 70 75 80
Asn Lys Gly Glu Arg Leu Asn Gln Asp Gln Leu Asp Ala Val Ser Lys
85 90 95
Tyr Gln Glu Val Thr Asn Asn Leu Glu Phe Ala Lys Glu Leu Gln Arg
100 105 110
Ser Phe Met Ala Leu Ser Gln Asp Ile Gln Lys Thr Ile Lys Lys Thr
115 120 125
Ala Arg Arg Glu Gln Leu Met Arg Glu Glu Ala Glu Gln Lys Arg Leu
130 135 140
Lys Thr Val Leu Glu Leu Gln Tyr Val Leu Asp Lys Leu Gly Asp Asp
145 150 155 160
Asp Val Arg Thr Asp Leu Lys Gln Gly Leu Ser Gly Val Pro Ile Leu
165 170 175
Ser Glu Glu Glu Leu Ser Leu Leu Asp Glu Phe Tyr Lys Leu Val Asp
180 185 190
Pro Glu Arg Asp Met Ser Leu Arg Leu Asn Glu Gln Tyr Glu His Ala
195 200 205
Ser Ile His Leu Trp Asp Leu Leu Glu Gly Lys Glu Lys Pro Val Cys
210 215 220
Gly Thr Thr Tyr Lys Ala Leu Lys Glu Ile Val Glu Arg Val Phe Gln
225 230 235 240
Ser Asn Tyr Phe Asp Ser Thr His Asn His Gln Asn Gly Leu Cys Glu
245 250 255
Glu Glu Glu Ala Ala Ser Ala Pro Thr Val Glu Asp Gln Val Ala Glu
260 265 270
Ala Glu Pro Glu Pro Ala Glu Glu Tyr Thr Glu Gln Ser Glu Val Glu
275 280 285
Ser Thr Glu Tyr Val Asn Arg Gln Phe Met Ala Glu Thr Gln Phe Ser
290 295 300
Ser Gly Glu Lys Glu Gln Val Asp Glu Trp Thr Val Glu Thr Val Glu
305 310 315 320
Val Val Asn Ser Leu Gln Gln Gln Pro Gln Ala Ala Ser Pro Ser Val
325 330 335
Pro Glu Pro His Ser Leu Thr Pro Val Ala Gln Ser Asp Pro Leu Val
340 345 350
Arg Arg Gln Arg Val Gln Asp Leu Met Ala Gln Met Gln Gly Pro Tyr
355 360 365
Asn Phe Ile Gln Asp Ser Met Leu Asp Phe Glu Asn Gln Thr Leu Asp
370 375 380
Pro Ala Ile Val Ser Ala Gln Pro Met Asn Pro Thr Gln Asn Met Asp
385 390 395 400
Met Pro Gln Leu Val Cys Pro Gln Val His Ser Glu Ser Arg Leu Ala
405 410 415
Gln Ser Asn Gln Val Pro Val Gln Pro Glu Ala Thr Gln Val Pro Leu
420 425 430
Val Ser Ser Thr Ser Glu Gly Tyr Thr Ala Ser Gln Pro Leu Tyr Gln
435 440 445
Pro Ser His Ala Thr Glu Gln Arg Pro Gln Lys Glu Pro Met Asp Gln
450 455 460
Ile Gln Ala Thr Ile Ser Leu Asn Thr Asp Gln Thr Thr Ala Ser Ser
465 470 475 480
Ser Leu Pro Ala Ala Ser Gln Pro Gln Val Phe Gln Ala Gly Thr Ser
485 490 495
Lys Pro Leu His Ser Ser Gly Ile Asn Val Asn Ala Ala Pro Phe Gln
500 505 510
Ser Met Gln Thr Val Phe Asn Met Asn Ala Pro Val Pro Pro Ala Asn
515 520 525
Glu Pro Glu Thr Leu Lys Gln Gln Ser Gln Tyr Gln Ala Thr Tyr Asn
530 535 540
Gln Ser Phe Ser Ser Gln Pro His Gln Val Glu Gln Thr Glu Leu Gln
545 550 555 560
Gln Asp Gln Leu Gln Thr Val Val Gly Thr Tyr His Gly Ser Gln Asp
565 570 575
Gln Pro His Gln Val Pro Gly Asn His Gln Gln Pro Pro Gln Gln Asn
580 585 590
Thr Gly Phe Pro Arg Ser Ser Gln Pro Tyr Tyr Asn Ser Arg Gly Val
595 600 605
Ser Arg Gly Gly Ser Arg Gly Ala Arg Gly Leu Met Asn Gly Tyr Arg
610 615 620
Gly Pro Ala Asn Gly Phe Arg Gly Gly Tyr Asp Gly Tyr Arg Pro Ser
625 630 635 640
Phe Ser Asn Thr Pro Asn Ser Gly Tyr Ser Gln Ser Gln Phe Thr Ala
645 650 655
Pro Arg Asp Tyr Ser Gly Tyr Gln Arg Asp Gly Tyr Gln Gln Asn Phe
660 665 670
Lys Arg Gly Ser Gly Gln Ser Gly Pro Arg Gly Ala Pro Arg Gly Arg
675 680 685
Gly Gly Pro Pro Arg Pro Asn Arg Gly Met Pro Gln Met Asn Thr Gln
690 695 700
Gln Val Asn
705
<210> 21
<211> 6141
<212> DNA
<213> 小鼠(Mus musculus)
<220>
<221> CDS
<222> (139)..(2262)
<400> 21
cccaccgcgc gcgcgcgtag ccgcctgccc gcccgcccgc tgcgcgtttt gtcccgcgtc 60
tctccccgtc cgtctcctga cttgctggtc ttgtccttcc ctcccgcttt tttcctctcc 120
tctcttctcg gtctaaag atg ccc tcg gcc acc agc cac agc gga agc ggc 171
Met Pro Ser Ala Thr Ser His Ser Gly Ser Gly
1 5 10
agc aaa tcg tcg gga ccg ccg ccg ccg tcc ggt tcc tcc ggg agt gag 219
Ser Lys Ser Ser Gly Pro Pro Pro Pro Ser Gly Ser Ser Gly Ser Glu
15 20 25
gcg gcg gcc ggg gca gct gcg ccg gct tct cag cat ccg gca acc ggc 267
Ala Ala Ala Gly Ala Ala Ala Pro Ala Ser Gln His Pro Ala Thr Gly
30 35 40
acc ggc gcc gtc cag acc gag gcc atg aag cag att ctc ggc gta atc 315
Thr Gly Ala Val Gln Thr Glu Ala Met Lys Gln Ile Leu Gly Val Ile
45 50 55
gac aag aaa ctt cgg aac ctg gag aag aaa aag ggt aaa ctt gat gat 363
Asp Lys Lys Leu Arg Asn Leu Glu Lys Lys Lys Gly Lys Leu Asp Asp
60 65 70 75
tac cag gaa cga atg aat aaa ggg gaa agg ctc aat caa gac cag ctg 411
Tyr Gln Glu Arg Met Asn Lys Gly Glu Arg Leu Asn Gln Asp Gln Leu
80 85 90
gat gcc gta tct aag tac cag gaa gtc aca aat aat ttg gag ttt gca 459
Asp Ala Val Ser Lys Tyr Gln Glu Val Thr Asn Asn Leu Glu Phe Ala
95 100 105
aag gaa tta cag agg agt ttc atg gca tta agt caa gat att cag aaa 507
Lys Glu Leu Gln Arg Ser Phe Met Ala Leu Ser Gln Asp Ile Gln Lys
110 115 120
aca ata aag aag aca gca cgt cgg gaa cag ctt atg aga gaa gaa gca 555
Thr Ile Lys Lys Thr Ala Arg Arg Glu Gln Leu Met Arg Glu Glu Ala
125 130 135
gaa cag aag cgc tta aaa act gta ctt gag tta cag tat gta ttg gat 603
Glu Gln Lys Arg Leu Lys Thr Val Leu Glu Leu Gln Tyr Val Leu Asp
140 145 150 155
aag ctg gga gat gat gat gtg aga aca gat ctg aaa caa ggt ttg agt 651
Lys Leu Gly Asp Asp Asp Val Arg Thr Asp Leu Lys Gln Gly Leu Ser
160 165 170
gga gtg cca ata ttg tct gag gag gag ttg tca ttg ctg gat gag ttc 699
Gly Val Pro Ile Leu Ser Glu Glu Glu Leu Ser Leu Leu Asp Glu Phe
175 180 185
tac aag ctc gta gat cct gag cgt gac atg agt tta agg tta aat gag 747
Tyr Lys Leu Val Asp Pro Glu Arg Asp Met Ser Leu Arg Leu Asn Glu
190 195 200
cag tat gaa cat gcc tca att cac ttg tgg gat ttg ctg gaa ggg aaa 795
Gln Tyr Glu His Ala Ser Ile His Leu Trp Asp Leu Leu Glu Gly Lys
205 210 215
gaa aag cct gtg tgt gga aca acc tat aaa gct cta aag gaa att gtt 843
Glu Lys Pro Val Cys Gly Thr Thr Tyr Lys Ala Leu Lys Glu Ile Val
220 225 230 235
gag cgt gtt ttc cag tca aac tac ttt gat agc act cac aat cat caa 891
Glu Arg Val Phe Gln Ser Asn Tyr Phe Asp Ser Thr His Asn His Gln
240 245 250
aat ggg ttg tgt gag gag gaa gag gcg gct tca gcg ccc aca gtg gag 939
Asn Gly Leu Cys Glu Glu Glu Glu Ala Ala Ser Ala Pro Thr Val Glu
255 260 265
gac cag gta gct gaa gct gaa cct gag cca gcg gaa gaa tac aca gag 987
Asp Gln Val Ala Glu Ala Glu Pro Glu Pro Ala Glu Glu Tyr Thr Glu
270 275 280
caa agt gag gtt gaa tca aca gag tat gtc aat agg cag ttc atg gca 1035
Gln Ser Glu Val Glu Ser Thr Glu Tyr Val Asn Arg Gln Phe Met Ala
285 290 295
gaa aca cag ttc agc agt ggt gag aag gag caa gtg gat gag tgg aca 1083
Glu Thr Gln Phe Ser Ser Gly Glu Lys Glu Gln Val Asp Glu Trp Thr
300 305 310 315
gtt gaa aca gtt gag gtt gta aac tca ctc cag cag caa cct cag gct 1131
Val Glu Thr Val Glu Val Val Asn Ser Leu Gln Gln Gln Pro Gln Ala
320 325 330
gcg tcc cct tca gtc cca gag ccc cac tct ttg act cca gtg gct cag 1179
Ala Ser Pro Ser Val Pro Glu Pro His Ser Leu Thr Pro Val Ala Gln
335 340 345
tca gat cca ctt gtg aga agg cag cgt gta caa gat ctt atg gca caa 1227
Ser Asp Pro Leu Val Arg Arg Gln Arg Val Gln Asp Leu Met Ala Gln
350 355 360
atg caa ggg ccc tat aat ttc ata cag gat tca atg ttg gat ttt gaa 1275
Met Gln Gly Pro Tyr Asn Phe Ile Gln Asp Ser Met Leu Asp Phe Glu
365 370 375
aat cag acg ctt gat cct gcc att gta tcc gca cag cct atg aac cct 1323
Asn Gln Thr Leu Asp Pro Ala Ile Val Ser Ala Gln Pro Met Asn Pro
380 385 390 395
acc cag aac atg gat atg cct cag ctg gtt tgc cct cag gtt cat tct 1371
Thr Gln Asn Met Asp Met Pro Gln Leu Val Cys Pro Gln Val His Ser
400 405 410
gaa tct aga ctt gcc caa tct aat caa gtt cct gta caa cca gaa gcc 1419
Glu Ser Arg Leu Ala Gln Ser Asn Gln Val Pro Val Gln Pro Glu Ala
415 420 425
aca cag gtt cct ttg gtt tca tcc aca agt gag ggg tat aca gca tct 1467
Thr Gln Val Pro Leu Val Ser Ser Thr Ser Glu Gly Tyr Thr Ala Ser
430 435 440
cag ccc ttg tac cag cca tct cat gct acg gag cag cgg ccg cag aaa 1515
Gln Pro Leu Tyr Gln Pro Ser His Ala Thr Glu Gln Arg Pro Gln Lys
445 450 455
gag cca atg gat cag att cag gca aca ata tct ttg aat aca gac cag 1563
Glu Pro Met Asp Gln Ile Gln Ala Thr Ile Ser Leu Asn Thr Asp Gln
460 465 470 475
act aca gca tcc tca tcc ctt cct gct gct tct cag cct caa gtg ttc 1611
Thr Thr Ala Ser Ser Ser Leu Pro Ala Ala Ser Gln Pro Gln Val Phe
480 485 490
cag gct ggg aca agt aaa cct ttg cac agc agt gga atc aat gta aat 1659
Gln Ala Gly Thr Ser Lys Pro Leu His Ser Ser Gly Ile Asn Val Asn
495 500 505
gca gct cca ttc cag tcc atg caa acg gtg ttc aat atg aat gct cca 1707
Ala Ala Pro Phe Gln Ser Met Gln Thr Val Phe Asn Met Asn Ala Pro
510 515 520
gtc cct cct gct aat gaa cca gaa acg tta aaa caa cag agt cag tac 1755
Val Pro Pro Ala Asn Glu Pro Glu Thr Leu Lys Gln Gln Ser Gln Tyr
525 530 535
cag gcc act tat aac cag agt ttt tcc agt cag cct cac caa gtg gaa 1803
Gln Ala Thr Tyr Asn Gln Ser Phe Ser Ser Gln Pro His Gln Val Glu
540 545 550 555
caa aca gag ctt caa caa gac caa ctg caa acg gtg gtt ggc act tac 1851
Gln Thr Glu Leu Gln Gln Asp Gln Leu Gln Thr Val Val Gly Thr Tyr
560 565 570
cat gga tcc cag gac cag cct cat caa gtg cct ggt aac cac cag caa 1899
His Gly Ser Gln Asp Gln Pro His Gln Val Pro Gly Asn His Gln Gln
575 580 585
ccc cca cag cag aac act ggc ttt cca cgt agc agt cag cct tat tac 1947
Pro Pro Gln Gln Asn Thr Gly Phe Pro Arg Ser Ser Gln Pro Tyr Tyr
590 595 600
aac agt cgt ggg gta tct cga gga ggg tct cgt ggt gcc aga ggc ttg 1995
Asn Ser Arg Gly Val Ser Arg Gly Gly Ser Arg Gly Ala Arg Gly Leu
605 610 615
atg aat gga tac agg ggc cct gcc aat gga ttt aga gga gga tat gat 2043
Met Asn Gly Tyr Arg Gly Pro Ala Asn Gly Phe Arg Gly Gly Tyr Asp
620 625 630 635
ggt tac cgc cct tca ttc tcg aac act cca aac agt ggt tat tca cag 2091
Gly Tyr Arg Pro Ser Phe Ser Asn Thr Pro Asn Ser Gly Tyr Ser Gln
640 645 650
tct cag ttc act gct ccc cgg gac tac tct ggt tac cag cgg gat gga 2139
Ser Gln Phe Thr Ala Pro Arg Asp Tyr Ser Gly Tyr Gln Arg Asp Gly
655 660 665
tat cag cag aat ttc aag cga ggc tct ggg cag agt gga cca cgg gga 2187
Tyr Gln Gln Asn Phe Lys Arg Gly Ser Gly Gln Ser Gly Pro Arg Gly
670 675 680
gcc cca cga ggt cgt gga ggg ccc cca aga ccc aac aga ggg atg ccg 2235
Ala Pro Arg Gly Arg Gly Gly Pro Pro Arg Pro Asn Arg Gly Met Pro
685 690 695
caa atg aac act cag caa gtg aat taa tgtgatacac aggattatgt 2282
Gln Met Asn Thr Gln Gln Val Asn
700 705
ttaatcgcca aaaacacact ggccagtgta ccataatatg ttaccagaag agttattatc 2342
tatttgttct ccctttcagg aaacttattg taaagggact gttttcatcc cataaagaca 2402
ggactgcaat tgtcagcttt acattacctg gatatggaag gaaactattt ttattctgca 2462
tgttctgtcc taagcgtcat cttgagcctt gcacacaata caatactcag attcctcacc 2522
cttgcttagg agtaaaacat tatatactta tggggtgata atatctccat agttagttga 2582
agtggcttgg aaaaaaaatg caagattgaa tttttgacct tggataaaat ctacaatcag 2642
ccctagaact attcagtggt aattgacaaa gttaaagcat tttctttgaa aggaagatgg 2702
aaggagtgga gtgtggttta gcaaaactgc atttcatagc tttcccatta aattggagca 2762
ccgacagatt aaaagcatac caaattatgc atgggtcctt actcacacaa gtgaggctgg 2822
ctaccagcct tgacatagca ctcactagtc ttctggccaa acgactgtga ttaaaacaca 2882
tgtaaattgc tctttagtag tggatactgt gtaagacaaa gccaaattgc aaatcaggct 2942
ttgattggct cttctggaaa atatgcatca aatatggggg ataatctgga tgggctgctg 3002
ctgtgctcaa tgtgaactat ttagatacct ttggaacact taacagtttc tctgaacaat 3062
gacttacatg gggattggtc ctgtttgtca ttcctcacca taattgcatt gtcatcacta 3122
atccttggat cttgctgtat tgttactcaa attggtaata ggtactgatg gaaatcgcta 3182
atggatggat aatcataaca cttttggtca catgttttct cctgcagcct gaaagttctt 3242
aaagaaaaag atatcaaatg cctgctgcta ccaccctttt aaattgctat ctttagaaaa 3302
gcaccggtat gtgttttaga ttcatttccc tgttttaggg aaatgacagg cagtagtttc 3362
agttctgatg gcaaaacaaa taaaaacatg tttctaaaag ttgtatcttg aaacactggt 3422
gttcaacagc tagcagctaa agtaattcaa cccatgcatt gctagtgtca cagcctttgg 3482
ttatgtctag tagctgtttc tgaagtattt tcatttatct tttgtcaaat ttaaccctgt 3542
ttgaattctc tcctttcctc aaggagacac ttatgttcaa agtgttgatt ctttgcctta 3602
ggtgcataga gagtagacag tttggagatg gaaaggttag cagtgactta gccatatgtt 3662
ctgtgttgga atttgtgcta gcagtttgag cactagctct gcgtgcctat gaactgaatg 3722
ctgcttgtcc cattccattt tatgtcatgg agaaataatt ccacttggta acacaaaggc 3782
taagttaatg ttattttctg tacagaaatt aaattttact tttagccttt tgtaaacttt 3842
tttttttttt ttccaagccg gtatcagcta ctcaaaacaa ttctcagata ttcatcatta 3902
gacaactgga gtttttgctg gttttgtagc ctactaaaac tgctgaggct gttgaacatt 3962
ccacattcaa aagttttgta gggtggtgga taatggggaa gcttcaatgt ttattttaaa 4022
ataaataaaa taagttcttg acttttctca tgtgtggtta tggtacatca tattggaagg 4082
gttatctgtt tacttttgcc aagactattt tgccagcacc tacacttgtg tgctttaaaa 4142
gacaactacc tgggatgtac cacaaccata tgttaattgt attttattgg gatggataaa 4202
atgtttgtgg tttattggat aatccctaga tggtgtgtta cgtgtgtaga atataatttt 4262
atgatagtaa gaaagcaaaa ttgaagaaaa taagtttagt attgaatttg agttctgaag 4322
tgaattcagg gaatgtctca cgtttcgggc ttctacccaa agtgtagggc agaaggtgta 4382
aaagttgttt gtagtttgac ttgtttattt tttaagttgc ttattccttt caacagcaac 4442
atatcattag ctgtcattct accattgcag ttctagtgag ttttaacgtc tgcattcaag 4502
actgttttaa aagcaacctc actggacaga gaactgctaa agtcttttcc ttaagatctg 4562
agtctttgtt actcagtatc ttctataata tgcaaatgct tgtctagagg cagaagacct 4622
tttgtttggt caagtgtgta ttttaccaga gtacagggaa ctgatggtcc tacatgtctc 4682
ttagtgtagt aagactataa aatcttttgt acatgcacaa ttcacagtat gtttagatac 4742
cacgtgtata atgccccccc ctcccccagg tagcatgcca ttgatgactt tttgcttagg 4802
gccattttat taccagggcc ttaatattcc taaaaagatg attttttttc atcctttctc 4862
ctcttttgat cattgtatct tgatattaaa aacatgacct tccaatgatt gtagtaaatt 4922
aacttctata gttcttttgt ctctatatgt attcatatat atgctattgt atagagactt 4982
caaggagaca tggagatgca tgcttattct caggttcatt cactaaggtg cttggcagac 5042
aaccagtttc taagtgcaga atgtagttaa gcagcttcat atatgtgcca ggcaatttgt 5102
tttgttaaat tttcatctac ttaaggaaat agggtattgt agcttaggct gatcataccc 5162
ttcatttcaa ccttaagctc tcaacctgca tccatccgac ttgagctatt aagtacttta 5222
gttttatcga gtataagtta acagaaaaag taaattaagc tttgccttta ctattttgaa 5282
tttatataca ttctggaaaa acttagaaac tgttgtatat ttcattagat taaattatat 5342
gaaaatgtga ttgtttatag caaagcctgt gagttgcata caccctaagg aaaactcctt 5402
aagtgctcct tgaagagaga agaaacaatt ctgggtctgg tctttttaag aacaaagcta 5462
gactactgta tgttagcact gtacattaat agtctgttgt gaagcttgag cagtttcctg 5522
catagccttg atccttcacc gttggcattg aaaatagcag tatccctgat gtacttaaaa 5582
cttaaagtca ggttttggta tatttatttg taagtcttaa tttcctctaa atactatatc 5642
tctttagcga gacaacctga aatttattag cacatttggg tatctcttgc ttggcattat 5702
ggccagtgtt aactattcag tggtgaaaaa attacccctc aagacactgg agtgacccca 5762
gatgtgtgta gtaagtggca tggttcaact gtgtggttaa tgataaatat atgacttagt 5822
cggtatgatc tggaaagact tgattgaaag ataattcagc tgacataagg atgagtgagg 5882
agtggcaaac tggataaaag agtcaagaga cctgtattcc agtgactcct gttttgttta 5942
agcattagca agatctgtct ggggaaactg gatagggcag ttttcttcca tgtttagttt 6002
ttgtctcaac atttggaagc tattgaaggt tttaaaatgg tgtgtattgt ttttttttgg 6062
ggggggggtg gccagaatag tgggtcatct aataaaactg ccatttaaaa gatcaaaaaa 6122
aaaaaaaaaa aaaaaaaaa 6141
<210> 22
<211> 707
<212> PRT
<213> 小鼠(Mus musculus)
<400> 22
Met Pro Ser Ala Thr Ser His Ser Gly Ser Gly Ser Lys Ser Ser Gly
1 5 10 15
Pro Pro Pro Pro Ser Gly Ser Ser Gly Ser Glu Ala Ala Ala Gly Ala
20 25 30
Ala Ala Pro Ala Ser Gln His Pro Ala Thr Gly Thr Gly Ala Val Gln
35 40 45
Thr Glu Ala Met Lys Gln Ile Leu Gly Val Ile Asp Lys Lys Leu Arg
50 55 60
Asn Leu Glu Lys Lys Lys Gly Lys Leu Asp Asp Tyr Gln Glu Arg Met
65 70 75 80
Asn Lys Gly Glu Arg Leu Asn Gln Asp Gln Leu Asp Ala Val Ser Lys
85 90 95
Tyr Gln Glu Val Thr Asn Asn Leu Glu Phe Ala Lys Glu Leu Gln Arg
100 105 110
Ser Phe Met Ala Leu Ser Gln Asp Ile Gln Lys Thr Ile Lys Lys Thr
115 120 125
Ala Arg Arg Glu Gln Leu Met Arg Glu Glu Ala Glu Gln Lys Arg Leu
130 135 140
Lys Thr Val Leu Glu Leu Gln Tyr Val Leu Asp Lys Leu Gly Asp Asp
145 150 155 160
Asp Val Arg Thr Asp Leu Lys Gln Gly Leu Ser Gly Val Pro Ile Leu
165 170 175
Ser Glu Glu Glu Leu Ser Leu Leu Asp Glu Phe Tyr Lys Leu Val Asp
180 185 190
Pro Glu Arg Asp Met Ser Leu Arg Leu Asn Glu Gln Tyr Glu His Ala
195 200 205
Ser Ile His Leu Trp Asp Leu Leu Glu Gly Lys Glu Lys Pro Val Cys
210 215 220
Gly Thr Thr Tyr Lys Ala Leu Lys Glu Ile Val Glu Arg Val Phe Gln
225 230 235 240
Ser Asn Tyr Phe Asp Ser Thr His Asn His Gln Asn Gly Leu Cys Glu
245 250 255
Glu Glu Glu Ala Ala Ser Ala Pro Thr Val Glu Asp Gln Val Ala Glu
260 265 270
Ala Glu Pro Glu Pro Ala Glu Glu Tyr Thr Glu Gln Ser Glu Val Glu
275 280 285
Ser Thr Glu Tyr Val Asn Arg Gln Phe Met Ala Glu Thr Gln Phe Ser
290 295 300
Ser Gly Glu Lys Glu Gln Val Asp Glu Trp Thr Val Glu Thr Val Glu
305 310 315 320
Val Val Asn Ser Leu Gln Gln Gln Pro Gln Ala Ala Ser Pro Ser Val
325 330 335
Pro Glu Pro His Ser Leu Thr Pro Val Ala Gln Ser Asp Pro Leu Val
340 345 350
Arg Arg Gln Arg Val Gln Asp Leu Met Ala Gln Met Gln Gly Pro Tyr
355 360 365
Asn Phe Ile Gln Asp Ser Met Leu Asp Phe Glu Asn Gln Thr Leu Asp
370 375 380
Pro Ala Ile Val Ser Ala Gln Pro Met Asn Pro Thr Gln Asn Met Asp
385 390 395 400
Met Pro Gln Leu Val Cys Pro Gln Val His Ser Glu Ser Arg Leu Ala
405 410 415
Gln Ser Asn Gln Val Pro Val Gln Pro Glu Ala Thr Gln Val Pro Leu
420 425 430
Val Ser Ser Thr Ser Glu Gly Tyr Thr Ala Ser Gln Pro Leu Tyr Gln
435 440 445
Pro Ser His Ala Thr Glu Gln Arg Pro Gln Lys Glu Pro Met Asp Gln
450 455 460
Ile Gln Ala Thr Ile Ser Leu Asn Thr Asp Gln Thr Thr Ala Ser Ser
465 470 475 480
Ser Leu Pro Ala Ala Ser Gln Pro Gln Val Phe Gln Ala Gly Thr Ser
485 490 495
Lys Pro Leu His Ser Ser Gly Ile Asn Val Asn Ala Ala Pro Phe Gln
500 505 510
Ser Met Gln Thr Val Phe Asn Met Asn Ala Pro Val Pro Pro Ala Asn
515 520 525
Glu Pro Glu Thr Leu Lys Gln Gln Ser Gln Tyr Gln Ala Thr Tyr Asn
530 535 540
Gln Ser Phe Ser Ser Gln Pro His Gln Val Glu Gln Thr Glu Leu Gln
545 550 555 560
Gln Asp Gln Leu Gln Thr Val Val Gly Thr Tyr His Gly Ser Gln Asp
565 570 575
Gln Pro His Gln Val Pro Gly Asn His Gln Gln Pro Pro Gln Gln Asn
580 585 590
Thr Gly Phe Pro Arg Ser Ser Gln Pro Tyr Tyr Asn Ser Arg Gly Val
595 600 605
Ser Arg Gly Gly Ser Arg Gly Ala Arg Gly Leu Met Asn Gly Tyr Arg
610 615 620
Gly Pro Ala Asn Gly Phe Arg Gly Gly Tyr Asp Gly Tyr Arg Pro Ser
625 630 635 640
Phe Ser Asn Thr Pro Asn Ser Gly Tyr Ser Gln Ser Gln Phe Thr Ala
645 650 655
Pro Arg Asp Tyr Ser Gly Tyr Gln Arg Asp Gly Tyr Gln Gln Asn Phe
660 665 670
Lys Arg Gly Ser Gly Gln Ser Gly Pro Arg Gly Ala Pro Arg Gly Arg
675 680 685
Gly Gly Pro Pro Arg Pro Asn Arg Gly Met Pro Gln Met Asn Thr Gln
690 695 700
Gln Val Asn
705
<210> 23
<211> 6114
<212> DNA
<213> 小鼠(Mus musculus)
<220>
<221> CDS
<222> (139)..(2235)
<400> 23
cccaccgcgc gcgcgcgtag ccgcctgccc gcccgcccgc tgcgcgtttt gtcccgcgtc 60
tctccccgtc cgtctcctga cttgctggtc ttgtccttcc ctcccgcttt tttcctctcc 120
tctcttctcg gtctaaag atg ccc tcg gcc acc agc cac agc gga agc ggc 171
Met Pro Ser Ala Thr Ser His Ser Gly Ser Gly
1 5 10
agc aaa tcg tcg gga ccg ccg ccg ccg tcc ggt tcc tcc ggg agt gag 219
Ser Lys Ser Ser Gly Pro Pro Pro Pro Ser Gly Ser Ser Gly Ser Glu
15 20 25
gcg gcg gcc ggg gca gct gcg ccg gct tct cag cat ccg gca acc ggc 267
Ala Ala Ala Gly Ala Ala Ala Pro Ala Ser Gln His Pro Ala Thr Gly
30 35 40
acc ggc gcc gtc cag acc gag gcc atg aag cag att ctc ggc gta atc 315
Thr Gly Ala Val Gln Thr Glu Ala Met Lys Gln Ile Leu Gly Val Ile
45 50 55
gac aag aaa ctt cgg aac ctg gag aag aaa aag ggt aaa ctt gat gat 363
Asp Lys Lys Leu Arg Asn Leu Glu Lys Lys Lys Gly Lys Leu Asp Asp
60 65 70 75
tac cag gaa cga atg aat aaa ggg gaa agg ctc aat caa gac cag ctg 411
Tyr Gln Glu Arg Met Asn Lys Gly Glu Arg Leu Asn Gln Asp Gln Leu
80 85 90
gat gcc gta tct aag tac cag gaa gtc aca aat aat ttg gag ttt gca 459
Asp Ala Val Ser Lys Tyr Gln Glu Val Thr Asn Asn Leu Glu Phe Ala
95 100 105
aag gaa tta cag agg agt ttc atg gca tta agt caa gat att cag aaa 507
Lys Glu Leu Gln Arg Ser Phe Met Ala Leu Ser Gln Asp Ile Gln Lys
110 115 120
aca ata aag aag aca gca cgt cgg gaa cag ctt atg aga gaa gaa gca 555
Thr Ile Lys Lys Thr Ala Arg Arg Glu Gln Leu Met Arg Glu Glu Ala
125 130 135
gaa cag aag cgc tta aaa act gta ctt gag tta cag tat gta ttg gat 603
Glu Gln Lys Arg Leu Lys Thr Val Leu Glu Leu Gln Tyr Val Leu Asp
140 145 150 155
aag ctg gga gat gat gat gtg aga aca gat ctg aaa caa ggt ttg agt 651
Lys Leu Gly Asp Asp Asp Val Arg Thr Asp Leu Lys Gln Gly Leu Ser
160 165 170
gga gtg cca ata ttg tct gag gag gag ttg tca ttg ctg gat gag ttc 699
Gly Val Pro Ile Leu Ser Glu Glu Glu Leu Ser Leu Leu Asp Glu Phe
175 180 185
tac aag ctc gta gat cct gag cgt gac atg agt tta agg tta aat gag 747
Tyr Lys Leu Val Asp Pro Glu Arg Asp Met Ser Leu Arg Leu Asn Glu
190 195 200
cag tat gaa cat gcc tca att cac ttg tgg gat ttg ctg gaa ggg aaa 795
Gln Tyr Glu His Ala Ser Ile His Leu Trp Asp Leu Leu Glu Gly Lys
205 210 215
gaa aag cct gtg tgt gga aca acc tat aaa gct cta aag gaa att gtt 843
Glu Lys Pro Val Cys Gly Thr Thr Tyr Lys Ala Leu Lys Glu Ile Val
220 225 230 235
gag cgt gtt ttc cag tca aac tac ttt gat agc act cac aat cat caa 891
Glu Arg Val Phe Gln Ser Asn Tyr Phe Asp Ser Thr His Asn His Gln
240 245 250
aat ggg ttg tgt gag gag gaa gag gcg gct tca gcg ccc aca gtg gag 939
Asn Gly Leu Cys Glu Glu Glu Glu Ala Ala Ser Ala Pro Thr Val Glu
255 260 265
gac cag gta gct gaa gct gaa cct gag cca gcg gaa gaa tac aca gag 987
Asp Gln Val Ala Glu Ala Glu Pro Glu Pro Ala Glu Glu Tyr Thr Glu
270 275 280
caa agt gag gtt gaa tca aca gag tat gtc aat agg cag ttc atg gca 1035
Gln Ser Glu Val Glu Ser Thr Glu Tyr Val Asn Arg Gln Phe Met Ala
285 290 295
gaa aca cag ttc agc agt ggt gag aag gag caa gtg gat gag tgg aca 1083
Glu Thr Gln Phe Ser Ser Gly Glu Lys Glu Gln Val Asp Glu Trp Thr
300 305 310 315
gtt gaa aca gtt gag gtt gta aac tca ctc cag cag caa cct cag gct 1131
Val Glu Thr Val Glu Val Val Asn Ser Leu Gln Gln Gln Pro Gln Ala
320 325 330
gcg tcc cct tca gtc cca gag ccc cac tct ttg act cca gtg gct cag 1179
Ala Ser Pro Ser Val Pro Glu Pro His Ser Leu Thr Pro Val Ala Gln
335 340 345
tca gat cca ctt gtg aga agg cag cgt gta caa gat ctt atg gca caa 1227
Ser Asp Pro Leu Val Arg Arg Gln Arg Val Gln Asp Leu Met Ala Gln
350 355 360
atg caa ggg ccc tat aat ttc ata cag acg ctt gat cct gcc att gta 1275
Met Gln Gly Pro Tyr Asn Phe Ile Gln Thr Leu Asp Pro Ala Ile Val
365 370 375
tcc gca cag cct atg aac cct acc cag aac atg gat atg cct cag ctg 1323
Ser Ala Gln Pro Met Asn Pro Thr Gln Asn Met Asp Met Pro Gln Leu
380 385 390 395
gtt tgc cct cag gtt cat tct gaa tct aga ctt gcc caa tct aat caa 1371
Val Cys Pro Gln Val His Ser Glu Ser Arg Leu Ala Gln Ser Asn Gln
400 405 410
gtt cct gta caa cca gaa gcc aca cag gtt cct ttg gtt tca tcc aca 1419
Val Pro Val Gln Pro Glu Ala Thr Gln Val Pro Leu Val Ser Ser Thr
415 420 425
agt gag ggg tat aca gca tct cag ccc ttg tac cag cca tct cat gct 1467
Ser Glu Gly Tyr Thr Ala Ser Gln Pro Leu Tyr Gln Pro Ser His Ala
430 435 440
acg gag cag cgg ccg cag aaa gag cca atg gat cag att cag gca aca 1515
Thr Glu Gln Arg Pro Gln Lys Glu Pro Met Asp Gln Ile Gln Ala Thr
445 450 455
ata tct ttg aat aca gac cag act aca gca tcc tca tcc ctt cct gct 1563
Ile Ser Leu Asn Thr Asp Gln Thr Thr Ala Ser Ser Ser Leu Pro Ala
460 465 470 475
gct tct cag cct caa gtg ttc cag gct ggg aca agt aaa cct ttg cac 1611
Ala Ser Gln Pro Gln Val Phe Gln Ala Gly Thr Ser Lys Pro Leu His
480 485 490
agc agt gga atc aat gta aat gca gct cca ttc cag tcc atg caa acg 1659
Ser Ser Gly Ile Asn Val Asn Ala Ala Pro Phe Gln Ser Met Gln Thr
495 500 505
gtg ttc aat atg aat gct cca gtc cct cct gct aat gaa cca gaa acg 1707
Val Phe Asn Met Asn Ala Pro Val Pro Pro Ala Asn Glu Pro Glu Thr
510 515 520
tta aaa caa cag agt cag tac cag gcc act tat aac cag agt ttt tcc 1755
Leu Lys Gln Gln Ser Gln Tyr Gln Ala Thr Tyr Asn Gln Ser Phe Ser
525 530 535
agt cag cct cac caa gtg gaa caa aca gag ctt caa caa gac caa ctg 1803
Ser Gln Pro His Gln Val Glu Gln Thr Glu Leu Gln Gln Asp Gln Leu
540 545 550 555
caa acg gtg gtt ggc act tac cat gga tcc cag gac cag cct cat caa 1851
Gln Thr Val Val Gly Thr Tyr His Gly Ser Gln Asp Gln Pro His Gln
560 565 570
gtg cct ggt aac cac cag caa ccc cca cag cag aac act ggc ttt cca 1899
Val Pro Gly Asn His Gln Gln Pro Pro Gln Gln Asn Thr Gly Phe Pro
575 580 585
cgt agc agt cag cct tat tac aac agt cgt ggg gta tct cga gga ggg 1947
Arg Ser Ser Gln Pro Tyr Tyr Asn Ser Arg Gly Val Ser Arg Gly Gly
590 595 600
tct cgt ggt gcc aga ggc ttg atg aat gga tac agg ggc cct gcc aat 1995
Ser Arg Gly Ala Arg Gly Leu Met Asn Gly Tyr Arg Gly Pro Ala Asn
605 610 615
gga ttt aga gga gga tat gat ggt tac cgc cct tca ttc tcg aac act 2043
Gly Phe Arg Gly Gly Tyr Asp Gly Tyr Arg Pro Ser Phe Ser Asn Thr
620 625 630 635
cca aac agt ggt tat tca cag tct cag ttc act gct ccc cgg gac tac 2091
Pro Asn Ser Gly Tyr Ser Gln Ser Gln Phe Thr Ala Pro Arg Asp Tyr
640 645 650
tct ggt tac cag cgg gat gga tat cag cag aat ttc aag cga ggc tct 2139
Ser Gly Tyr Gln Arg Asp Gly Tyr Gln Gln Asn Phe Lys Arg Gly Ser
655 660 665
ggg cag agt gga cca cgg gga gcc cca cga ggt cgt gga ggg ccc cca 2187
Gly Gln Ser Gly Pro Arg Gly Ala Pro Arg Gly Arg Gly Gly Pro Pro
670 675 680
aga ccc aac aga ggg atg ccg caa atg aac act cag caa gtg aat taa 2235
Arg Pro Asn Arg Gly Met Pro Gln Met Asn Thr Gln Gln Val Asn
685 690 695
tgtgatacac aggattatgt ttaatcgcca aaaacacact ggccagtgta ccataatatg 2295
ttaccagaag agttattatc tatttgttct ccctttcagg aaacttattg taaagggact 2355
gttttcatcc cataaagaca ggactgcaat tgtcagcttt acattacctg gatatggaag 2415
gaaactattt ttattctgca tgttctgtcc taagcgtcat cttgagcctt gcacacaata 2475
caatactcag attcctcacc cttgcttagg agtaaaacat tatatactta tggggtgata 2535
atatctccat agttagttga agtggcttgg aaaaaaaatg caagattgaa tttttgacct 2595
tggataaaat ctacaatcag ccctagaact attcagtggt aattgacaaa gttaaagcat 2655
tttctttgaa aggaagatgg aaggagtgga gtgtggttta gcaaaactgc atttcatagc 2715
tttcccatta aattggagca ccgacagatt aaaagcatac caaattatgc atgggtcctt 2775
actcacacaa gtgaggctgg ctaccagcct tgacatagca ctcactagtc ttctggccaa 2835
acgactgtga ttaaaacaca tgtaaattgc tctttagtag tggatactgt gtaagacaaa 2895
gccaaattgc aaatcaggct ttgattggct cttctggaaa atatgcatca aatatggggg 2955
ataatctgga tgggctgctg ctgtgctcaa tgtgaactat ttagatacct ttggaacact 3015
taacagtttc tctgaacaat gacttacatg gggattggtc ctgtttgtca ttcctcacca 3075
taattgcatt gtcatcacta atccttggat cttgctgtat tgttactcaa attggtaata 3135
ggtactgatg gaaatcgcta atggatggat aatcataaca cttttggtca catgttttct 3195
cctgcagcct gaaagttctt aaagaaaaag atatcaaatg cctgctgcta ccaccctttt 3255
aaattgctat ctttagaaaa gcaccggtat gtgttttaga ttcatttccc tgttttaggg 3315
aaatgacagg cagtagtttc agttctgatg gcaaaacaaa taaaaacatg tttctaaaag 3375
ttgtatcttg aaacactggt gttcaacagc tagcagctaa agtaattcaa cccatgcatt 3435
gctagtgtca cagcctttgg ttatgtctag tagctgtttc tgaagtattt tcatttatct 3495
tttgtcaaat ttaaccctgt ttgaattctc tcctttcctc aaggagacac ttatgttcaa 3555
agtgttgatt ctttgcctta ggtgcataga gagtagacag tttggagatg gaaaggttag 3615
cagtgactta gccatatgtt ctgtgttgga atttgtgcta gcagtttgag cactagctct 3675
gcgtgcctat gaactgaatg ctgcttgtcc cattccattt tatgtcatgg agaaataatt 3735
ccacttggta acacaaaggc taagttaatg ttattttctg tacagaaatt aaattttact 3795
tttagccttt tgtaaacttt tttttttttt ttccaagccg gtatcagcta ctcaaaacaa 3855
ttctcagata ttcatcatta gacaactgga gtttttgctg gttttgtagc ctactaaaac 3915
tgctgaggct gttgaacatt ccacattcaa aagttttgta gggtggtgga taatggggaa 3975
gcttcaatgt ttattttaaa ataaataaaa taagttcttg acttttctca tgtgtggtta 4035
tggtacatca tattggaagg gttatctgtt tacttttgcc aagactattt tgccagcacc 4095
tacacttgtg tgctttaaaa gacaactacc tgggatgtac cacaaccata tgttaattgt 4155
attttattgg gatggataaa atgtttgtgg tttattggat aatccctaga tggtgtgtta 4215
cgtgtgtaga atataatttt atgatagtaa gaaagcaaaa ttgaagaaaa taagtttagt 4275
attgaatttg agttctgaag tgaattcagg gaatgtctca cgtttcgggc ttctacccaa 4335
agtgtagggc agaaggtgta aaagttgttt gtagtttgac ttgtttattt tttaagttgc 4395
ttattccttt caacagcaac atatcattag ctgtcattct accattgcag ttctagtgag 4455
ttttaacgtc tgcattcaag actgttttaa aagcaacctc actggacaga gaactgctaa 4515
agtcttttcc ttaagatctg agtctttgtt actcagtatc ttctataata tgcaaatgct 4575
tgtctagagg cagaagacct tttgtttggt caagtgtgta ttttaccaga gtacagggaa 4635
ctgatggtcc tacatgtctc ttagtgtagt aagactataa aatcttttgt acatgcacaa 4695
ttcacagtat gtttagatac cacgtgtata atgccccccc ctcccccagg tagcatgcca 4755
ttgatgactt tttgcttagg gccattttat taccagggcc ttaatattcc taaaaagatg 4815
attttttttc atcctttctc ctcttttgat cattgtatct tgatattaaa aacatgacct 4875
tccaatgatt gtagtaaatt aacttctata gttcttttgt ctctatatgt attcatatat 4935
atgctattgt atagagactt caaggagaca tggagatgca tgcttattct caggttcatt 4995
cactaaggtg cttggcagac aaccagtttc taagtgcaga atgtagttaa gcagcttcat 5055
atatgtgcca ggcaatttgt tttgttaaat tttcatctac ttaaggaaat agggtattgt 5115
agcttaggct gatcataccc ttcatttcaa ccttaagctc tcaacctgca tccatccgac 5175
ttgagctatt aagtacttta gttttatcga gtataagtta acagaaaaag taaattaagc 5235
tttgccttta ctattttgaa tttatataca ttctggaaaa acttagaaac tgttgtatat 5295
ttcattagat taaattatat gaaaatgtga ttgtttatag caaagcctgt gagttgcata 5355
caccctaagg aaaactcctt aagtgctcct tgaagagaga agaaacaatt ctgggtctgg 5415
tctttttaag aacaaagcta gactactgta tgttagcact gtacattaat agtctgttgt 5475
gaagcttgag cagtttcctg catagccttg atccttcacc gttggcattg aaaatagcag 5535
tatccctgat gtacttaaaa cttaaagtca ggttttggta tatttatttg taagtcttaa 5595
tttcctctaa atactatatc tctttagcga gacaacctga aatttattag cacatttggg 5655
tatctcttgc ttggcattat ggccagtgtt aactattcag tggtgaaaaa attacccctc 5715
aagacactgg agtgacccca gatgtgtgta gtaagtggca tggttcaact gtgtggttaa 5775
tgataaatat atgacttagt cggtatgatc tggaaagact tgattgaaag ataattcagc 5835
tgacataagg atgagtgagg agtggcaaac tggataaaag agtcaagaga cctgtattcc 5895
agtgactcct gttttgttta agcattagca agatctgtct ggggaaactg gatagggcag 5955
ttttcttcca tgtttagttt ttgtctcaac atttggaagc tattgaaggt tttaaaatgg 6015
tgtgtattgt ttttttttgg ggggggggtg gccagaatag tgggtcatct aataaaactg 6075
ccatttaaaa gatcaaaaaa aaaaaaaaaa aaaaaaaaa 6114
<210> 24
<211> 698
<212> PRT
<213> 小鼠(Mus musculus)
<400> 24
Met Pro Ser Ala Thr Ser His Ser Gly Ser Gly Ser Lys Ser Ser Gly
1 5 10 15
Pro Pro Pro Pro Ser Gly Ser Ser Gly Ser Glu Ala Ala Ala Gly Ala
20 25 30
Ala Ala Pro Ala Ser Gln His Pro Ala Thr Gly Thr Gly Ala Val Gln
35 40 45
Thr Glu Ala Met Lys Gln Ile Leu Gly Val Ile Asp Lys Lys Leu Arg
50 55 60
Asn Leu Glu Lys Lys Lys Gly Lys Leu Asp Asp Tyr Gln Glu Arg Met
65 70 75 80
Asn Lys Gly Glu Arg Leu Asn Gln Asp Gln Leu Asp Ala Val Ser Lys
85 90 95
Tyr Gln Glu Val Thr Asn Asn Leu Glu Phe Ala Lys Glu Leu Gln Arg
100 105 110
Ser Phe Met Ala Leu Ser Gln Asp Ile Gln Lys Thr Ile Lys Lys Thr
115 120 125
Ala Arg Arg Glu Gln Leu Met Arg Glu Glu Ala Glu Gln Lys Arg Leu
130 135 140
Lys Thr Val Leu Glu Leu Gln Tyr Val Leu Asp Lys Leu Gly Asp Asp
145 150 155 160
Asp Val Arg Thr Asp Leu Lys Gln Gly Leu Ser Gly Val Pro Ile Leu
165 170 175
Ser Glu Glu Glu Leu Ser Leu Leu Asp Glu Phe Tyr Lys Leu Val Asp
180 185 190
Pro Glu Arg Asp Met Ser Leu Arg Leu Asn Glu Gln Tyr Glu His Ala
195 200 205
Ser Ile His Leu Trp Asp Leu Leu Glu Gly Lys Glu Lys Pro Val Cys
210 215 220
Gly Thr Thr Tyr Lys Ala Leu Lys Glu Ile Val Glu Arg Val Phe Gln
225 230 235 240
Ser Asn Tyr Phe Asp Ser Thr His Asn His Gln Asn Gly Leu Cys Glu
245 250 255
Glu Glu Glu Ala Ala Ser Ala Pro Thr Val Glu Asp Gln Val Ala Glu
260 265 270
Ala Glu Pro Glu Pro Ala Glu Glu Tyr Thr Glu Gln Ser Glu Val Glu
275 280 285
Ser Thr Glu Tyr Val Asn Arg Gln Phe Met Ala Glu Thr Gln Phe Ser
290 295 300
Ser Gly Glu Lys Glu Gln Val Asp Glu Trp Thr Val Glu Thr Val Glu
305 310 315 320
Val Val Asn Ser Leu Gln Gln Gln Pro Gln Ala Ala Ser Pro Ser Val
325 330 335
Pro Glu Pro His Ser Leu Thr Pro Val Ala Gln Ser Asp Pro Leu Val
340 345 350
Arg Arg Gln Arg Val Gln Asp Leu Met Ala Gln Met Gln Gly Pro Tyr
355 360 365
Asn Phe Ile Gln Thr Leu Asp Pro Ala Ile Val Ser Ala Gln Pro Met
370 375 380
Asn Pro Thr Gln Asn Met Asp Met Pro Gln Leu Val Cys Pro Gln Val
385 390 395 400
His Ser Glu Ser Arg Leu Ala Gln Ser Asn Gln Val Pro Val Gln Pro
405 410 415
Glu Ala Thr Gln Val Pro Leu Val Ser Ser Thr Ser Glu Gly Tyr Thr
420 425 430
Ala Ser Gln Pro Leu Tyr Gln Pro Ser His Ala Thr Glu Gln Arg Pro
435 440 445
Gln Lys Glu Pro Met Asp Gln Ile Gln Ala Thr Ile Ser Leu Asn Thr
450 455 460
Asp Gln Thr Thr Ala Ser Ser Ser Leu Pro Ala Ala Ser Gln Pro Gln
465 470 475 480
Val Phe Gln Ala Gly Thr Ser Lys Pro Leu His Ser Ser Gly Ile Asn
485 490 495
Val Asn Ala Ala Pro Phe Gln Ser Met Gln Thr Val Phe Asn Met Asn
500 505 510
Ala Pro Val Pro Pro Ala Asn Glu Pro Glu Thr Leu Lys Gln Gln Ser
515 520 525
Gln Tyr Gln Ala Thr Tyr Asn Gln Ser Phe Ser Ser Gln Pro His Gln
530 535 540
Val Glu Gln Thr Glu Leu Gln Gln Asp Gln Leu Gln Thr Val Val Gly
545 550 555 560
Thr Tyr His Gly Ser Gln Asp Gln Pro His Gln Val Pro Gly Asn His
565 570 575
Gln Gln Pro Pro Gln Gln Asn Thr Gly Phe Pro Arg Ser Ser Gln Pro
580 585 590
Tyr Tyr Asn Ser Arg Gly Val Ser Arg Gly Gly Ser Arg Gly Ala Arg
595 600 605
Gly Leu Met Asn Gly Tyr Arg Gly Pro Ala Asn Gly Phe Arg Gly Gly
610 615 620
Tyr Asp Gly Tyr Arg Pro Ser Phe Ser Asn Thr Pro Asn Ser Gly Tyr
625 630 635 640
Ser Gln Ser Gln Phe Thr Ala Pro Arg Asp Tyr Ser Gly Tyr Gln Arg
645 650 655
Asp Gly Tyr Gln Gln Asn Phe Lys Arg Gly Ser Gly Gln Ser Gly Pro
660 665 670
Arg Gly Ala Pro Arg Gly Arg Gly Gly Pro Pro Arg Pro Asn Arg Gly
675 680 685
Met Pro Gln Met Asn Thr Gln Gln Val Asn
690 695
<210> 25
<211> 3548
<212> DNA
<213> 小鼠(Mus musculus)
<220>
<221> CDS
<222> (179)..(2257)
<400> 25
gctggctggc taagtccctc ccgcgccggc tcttgtccca ctaggagcag ctcagagccg 60
cggggacagg gcgaagcggc ctgcgcccac ggagcgcacg tctctgttct caacgcagca 120
ccacccttgc ccccctcggc tgcccactcc agacgtccag cggctccgcg cgcgcacg 178
atg ccc tcg gcc acc agc cac agc gga agc ggc agc aaa tcg tcg gga 226
Met Pro Ser Ala Thr Ser His Ser Gly Ser Gly Ser Lys Ser Ser Gly
1 5 10 15
ccg ccg ccg ccg tcc ggt tcc tcc ggg agt gag gcg gcg gcc ggg gca 274
Pro Pro Pro Pro Ser Gly Ser Ser Gly Ser Glu Ala Ala Ala Gly Ala
20 25 30
gct gcg ccg gct tct cag cat ccg gca acc ggc acc ggc gcc gtc cag 322
Ala Ala Pro Ala Ser Gln His Pro Ala Thr Gly Thr Gly Ala Val Gln
35 40 45
acc gag gcc atg aag cag att ctc ggc gta atc gac aag aaa ctt cgg 370
Thr Glu Ala Met Lys Gln Ile Leu Gly Val Ile Asp Lys Lys Leu Arg
50 55 60
aac ctg gag aag aaa aag ggt aaa ctt gat gat tac cag gaa cga atg 418
Asn Leu Glu Lys Lys Lys Gly Lys Leu Asp Asp Tyr Gln Glu Arg Met
65 70 75 80
aat aaa ggg gaa agg ctc aat caa gac cag ctg gat gcc gta tct aag 466
Asn Lys Gly Glu Arg Leu Asn Gln Asp Gln Leu Asp Ala Val Ser Lys
85 90 95
tac cag gaa gtc aca aat aat ttg gag ttt gca aag gaa tta cag agg 514
Tyr Gln Glu Val Thr Asn Asn Leu Glu Phe Ala Lys Glu Leu Gln Arg
100 105 110
agt ttc atg gca tta agt caa gat att cag aaa aca ata aag aag aca 562
Ser Phe Met Ala Leu Ser Gln Asp Ile Gln Lys Thr Ile Lys Lys Thr
115 120 125
gca cgt cgg gaa cag ctt atg aga gaa gaa gca gaa cag aag cgc tta 610
Ala Arg Arg Glu Gln Leu Met Arg Glu Glu Ala Glu Gln Lys Arg Leu
130 135 140
aaa act gta ctt gag tta cag tat gta ttg gat aag ctg gga gat gat 658
Lys Thr Val Leu Glu Leu Gln Tyr Val Leu Asp Lys Leu Gly Asp Asp
145 150 155 160
gat gtg aga aca gat ctg aaa caa ggt ttg agt gga gtg cca ata ttg 706
Asp Val Arg Thr Asp Leu Lys Gln Gly Leu Ser Gly Val Pro Ile Leu
165 170 175
tct gag gag gag ttg tca ttg ctg gat gag ttc tac aag ctc gta gat 754
Ser Glu Glu Glu Leu Ser Leu Leu Asp Glu Phe Tyr Lys Leu Val Asp
180 185 190
cct gag cgt gac atg agt tta agg tta aat gag cag tat gaa cat gcc 802
Pro Glu Arg Asp Met Ser Leu Arg Leu Asn Glu Gln Tyr Glu His Ala
195 200 205
tca att cac ttg tgg gat ttg ctg gaa ggg aaa gaa aag cct gtg tgt 850
Ser Ile His Leu Trp Asp Leu Leu Glu Gly Lys Glu Lys Pro Val Cys
210 215 220
gga aca acc tat aaa gct cta aag gaa att gtt gag cgt gtt ttc cag 898
Gly Thr Thr Tyr Lys Ala Leu Lys Glu Ile Val Glu Arg Val Phe Gln
225 230 235 240
tca aac tac ttt gat agc act cac aat cat caa aat ggg ttg tgt gag 946
Ser Asn Tyr Phe Asp Ser Thr His Asn His Gln Asn Gly Leu Cys Glu
245 250 255
gag gaa gag gcg gct tca gcg ccc aca gtg gag gac cag gta gct gaa 994
Glu Glu Glu Ala Ala Ser Ala Pro Thr Val Glu Asp Gln Val Ala Glu
260 265 270
gct gaa cct gag cca gcg gaa gaa tac aca gag caa agt gag gtt gaa 1042
Ala Glu Pro Glu Pro Ala Glu Glu Tyr Thr Glu Gln Ser Glu Val Glu
275 280 285
tca aca gag tat gtc aat agg cag ttc atg gca gaa aca cag ttc agc 1090
Ser Thr Glu Tyr Val Asn Arg Gln Phe Met Ala Glu Thr Gln Phe Ser
290 295 300
agt ggt gag aag gag caa gtg gat gag tgg aca gtt gaa aca gtt gag 1138
Ser Gly Glu Lys Glu Gln Val Asp Glu Trp Thr Val Glu Thr Val Glu
305 310 315 320
gtt gta aac tca ctc cag cag caa cct cag gct gcg tcc cct tca gtc 1186
Val Val Asn Ser Leu Gln Gln Gln Pro Gln Ala Ala Ser Pro Ser Val
325 330 335
cca gag ccc cac tct ttg act cca gtg gct cag tca gat cca ctt gtg 1234
Pro Glu Pro His Ser Leu Thr Pro Val Ala Gln Ser Asp Pro Leu Val
340 345 350
aga agg cag cgt gta caa gat ctt atg gca caa atg caa ggg ccc tat 1282
Arg Arg Gln Arg Val Gln Asp Leu Met Ala Gln Met Gln Gly Pro Tyr
355 360 365
aat ttc ata cag gat tca atg ttg gat ttt gaa aat cag acg ctt gat 1330
Asn Phe Ile Gln Asp Ser Met Leu Asp Phe Glu Asn Gln Thr Leu Asp
370 375 380
cct gcc att gta tcc gca cag cct atg aac cct acc cag aac atg gat 1378
Pro Ala Ile Val Ser Ala Gln Pro Met Asn Pro Thr Gln Asn Met Asp
385 390 395 400
atg cct cag ctg gtt tgc cct cag gtt cat tct gaa tct aga ctt gcc 1426
Met Pro Gln Leu Val Cys Pro Gln Val His Ser Glu Ser Arg Leu Ala
405 410 415
caa tct aat caa gtt cct gta caa cca gaa gcc aca cag gtt cct ttg 1474
Gln Ser Asn Gln Val Pro Val Gln Pro Glu Ala Thr Gln Val Pro Leu
420 425 430
gtt tca tcc aca agt gag ggg tat aca gca tct cag ccc ttg tac cag 1522
Val Ser Ser Thr Ser Glu Gly Tyr Thr Ala Ser Gln Pro Leu Tyr Gln
435 440 445
cca tct cat gct acg gag cag cgg ccg cag aaa gag cca atg gat cag 1570
Pro Ser His Ala Thr Glu Gln Arg Pro Gln Lys Glu Pro Met Asp Gln
450 455 460
att cag gca aca ata tct ttg aat aca gac cag act aca gca tcc tca 1618
Ile Gln Ala Thr Ile Ser Leu Asn Thr Asp Gln Thr Thr Ala Ser Ser
465 470 475 480
tcc ctt cct gct gct tct cag cct caa gtg ttc cag gct ggg aca agt 1666
Ser Leu Pro Ala Ala Ser Gln Pro Gln Val Phe Gln Ala Gly Thr Ser
485 490 495
aaa cct ttg cac agc agt gga atc aat gta aat gca gct cca ttc cag 1714
Lys Pro Leu His Ser Ser Gly Ile Asn Val Asn Ala Ala Pro Phe Gln
500 505 510
tcc atg caa acg gtg ttc aat atg aat gct cca gtc cct cct gct aat 1762
Ser Met Gln Thr Val Phe Asn Met Asn Ala Pro Val Pro Pro Ala Asn
515 520 525
gaa cca gaa acg tta aaa caa cag agt cag tac cag gcc act tat aac 1810
Glu Pro Glu Thr Leu Lys Gln Gln Ser Gln Tyr Gln Ala Thr Tyr Asn
530 535 540
cag agt ttt tcc agt cag cct cac caa gtg gaa caa aca gag ctt caa 1858
Gln Ser Phe Ser Ser Gln Pro His Gln Val Glu Gln Thr Glu Leu Gln
545 550 555 560
caa gac caa ctg caa acg gtg gtt ggc act tac cat gga tcc cag gac 1906
Gln Asp Gln Leu Gln Thr Val Val Gly Thr Tyr His Gly Ser Gln Asp
565 570 575
cag cct cat caa gtg cct ggt aac cac cag caa ccc cca cag cag aac 1954
Gln Pro His Gln Val Pro Gly Asn His Gln Gln Pro Pro Gln Gln Asn
580 585 590
act ggc ttt cca cgt agc agt cag cct tat tac aac agt cgt ggg gta 2002
Thr Gly Phe Pro Arg Ser Ser Gln Pro Tyr Tyr Asn Ser Arg Gly Val
595 600 605
tct cga gga ggg tct cgt ggt gcc aga ggc ttg atg aat gga tac agg 2050
Ser Arg Gly Gly Ser Arg Gly Ala Arg Gly Leu Met Asn Gly Tyr Arg
610 615 620
ggc cct gcc aat gga ttt aga gga gga tat gat ggt tac cgc cct tca 2098
Gly Pro Ala Asn Gly Phe Arg Gly Gly Tyr Asp Gly Tyr Arg Pro Ser
625 630 635 640
ttc tcg aac act cca aac agt ggt tat tca cag tct cag ttc act gct 2146
Phe Ser Asn Thr Pro Asn Ser Gly Tyr Ser Gln Ser Gln Phe Thr Ala
645 650 655
ccc cgg gac tac tct ggt tac cag cgg gat gga tat cag cag aat ttc 2194
Pro Arg Asp Tyr Ser Gly Tyr Gln Arg Asp Gly Tyr Gln Gln Asn Phe
660 665 670
aag cga ggc tct ggg cag agt gga cca cgg gga gcc cca cga ggt aat 2242
Lys Arg Gly Ser Gly Gln Ser Gly Pro Arg Gly Ala Pro Arg Gly Asn
675 680 685
ata ttg tgg tgg tga tcctagctcc tatgtggagc ttctgttctg gccttggaag 2297
Ile Leu Trp Trp
690
aactgttcat agtccgcatg taggttacat gttaggaata catttatctt ttccagactt 2357
gttgctaaag attaaatgaa atgctctgtt tctaaaattt catcttgaat ccaaatttta 2417
atttttgaat gactttccct gctgttgtct tcaaaatcag aacattttct ctgcctcaga 2477
aaagcgtttt tccaactgga aatttatttt tcaggtctta aaacctgcta aatgttttta 2537
ggaagtacct actgaaactt tttgtaagac atttttggaa cgagcttgaa catttatata 2597
aatttattac cctctttgat ttttgaaaca tgcatattat atttaggctg agaagccctt 2657
caaatggcca gataagccac agttttagct agagaaccat ttagaattga cataactaat 2717
ctaaacttga acacttttag gaccaatgtt agtgttctaa ataccaacat atttctgatg 2777
tttaaacaga tctcccaaat tcttaggacc ttgatgtcat taaaatttag aatgacaagc 2837
ttaagaggct ttagtttcat ttgtttttca agtaatgaaa aataatttct tacatgggca 2897
gatagttaat ttgttgaaca attacaggta gcatttcatg taatctgatg ttctaaatgg 2957
ttctcttatt gaaggaggtt aaagaattag gtttcttaca gtttttggct ggccatgaca 3017
tgtataaaat gtatattaag gaggaattat aaagtacttt aatttgaatg ctagtggcaa 3077
ttgatcatta agaaagtact ttaaagcaaa aggttaatgg gtcatctggg aaaaatactg 3137
aagtatcaaa ggtatttgca tgtgaatgtg ggttatgttc ttctatccca ccttgtagca 3197
tattctatga aagttgagtt aaatgatagc taaaatatct gtttcaacag catgtaaaaa 3257
gttattttaa ctgttacaag tcattataca attttgaatg ttctgtagtt tctttttaac 3317
agtttaggta caaaggtctg ttttcattct ggtgcttttt attaattttg atagtatgat 3377
gtcacttcct attgaaatgt aagctagcgt gtaccttaga atgtgagctc catgagagca 3437
ggtaccttgt ttgtcttcac tgctgtatct attcccaacg cctcatgaca gtgcctggca 3497
catagtaggc actcaataaa tacttgttga atgaatgaaa aaaaaaaaaa a 3548
<210> 26
<211> 692
<212> PRT
<213> 小鼠(Mus musculus)
<400> 26
Met Pro Ser Ala Thr Ser His Ser Gly Ser Gly Ser Lys Ser Ser Gly
1 5 10 15
Pro Pro Pro Pro Ser Gly Ser Ser Gly Ser Glu Ala Ala Ala Gly Ala
20 25 30
Ala Ala Pro Ala Ser Gln His Pro Ala Thr Gly Thr Gly Ala Val Gln
35 40 45
Thr Glu Ala Met Lys Gln Ile Leu Gly Val Ile Asp Lys Lys Leu Arg
50 55 60
Asn Leu Glu Lys Lys Lys Gly Lys Leu Asp Asp Tyr Gln Glu Arg Met
65 70 75 80
Asn Lys Gly Glu Arg Leu Asn Gln Asp Gln Leu Asp Ala Val Ser Lys
85 90 95
Tyr Gln Glu Val Thr Asn Asn Leu Glu Phe Ala Lys Glu Leu Gln Arg
100 105 110
Ser Phe Met Ala Leu Ser Gln Asp Ile Gln Lys Thr Ile Lys Lys Thr
115 120 125
Ala Arg Arg Glu Gln Leu Met Arg Glu Glu Ala Glu Gln Lys Arg Leu
130 135 140
Lys Thr Val Leu Glu Leu Gln Tyr Val Leu Asp Lys Leu Gly Asp Asp
145 150 155 160
Asp Val Arg Thr Asp Leu Lys Gln Gly Leu Ser Gly Val Pro Ile Leu
165 170 175
Ser Glu Glu Glu Leu Ser Leu Leu Asp Glu Phe Tyr Lys Leu Val Asp
180 185 190
Pro Glu Arg Asp Met Ser Leu Arg Leu Asn Glu Gln Tyr Glu His Ala
195 200 205
Ser Ile His Leu Trp Asp Leu Leu Glu Gly Lys Glu Lys Pro Val Cys
210 215 220
Gly Thr Thr Tyr Lys Ala Leu Lys Glu Ile Val Glu Arg Val Phe Gln
225 230 235 240
Ser Asn Tyr Phe Asp Ser Thr His Asn His Gln Asn Gly Leu Cys Glu
245 250 255
Glu Glu Glu Ala Ala Ser Ala Pro Thr Val Glu Asp Gln Val Ala Glu
260 265 270
Ala Glu Pro Glu Pro Ala Glu Glu Tyr Thr Glu Gln Ser Glu Val Glu
275 280 285
Ser Thr Glu Tyr Val Asn Arg Gln Phe Met Ala Glu Thr Gln Phe Ser
290 295 300
Ser Gly Glu Lys Glu Gln Val Asp Glu Trp Thr Val Glu Thr Val Glu
305 310 315 320
Val Val Asn Ser Leu Gln Gln Gln Pro Gln Ala Ala Ser Pro Ser Val
325 330 335
Pro Glu Pro His Ser Leu Thr Pro Val Ala Gln Ser Asp Pro Leu Val
340 345 350
Arg Arg Gln Arg Val Gln Asp Leu Met Ala Gln Met Gln Gly Pro Tyr
355 360 365
Asn Phe Ile Gln Asp Ser Met Leu Asp Phe Glu Asn Gln Thr Leu Asp
370 375 380
Pro Ala Ile Val Ser Ala Gln Pro Met Asn Pro Thr Gln Asn Met Asp
385 390 395 400
Met Pro Gln Leu Val Cys Pro Gln Val His Ser Glu Ser Arg Leu Ala
405 410 415
Gln Ser Asn Gln Val Pro Val Gln Pro Glu Ala Thr Gln Val Pro Leu
420 425 430
Val Ser Ser Thr Ser Glu Gly Tyr Thr Ala Ser Gln Pro Leu Tyr Gln
435 440 445
Pro Ser His Ala Thr Glu Gln Arg Pro Gln Lys Glu Pro Met Asp Gln
450 455 460
Ile Gln Ala Thr Ile Ser Leu Asn Thr Asp Gln Thr Thr Ala Ser Ser
465 470 475 480
Ser Leu Pro Ala Ala Ser Gln Pro Gln Val Phe Gln Ala Gly Thr Ser
485 490 495
Lys Pro Leu His Ser Ser Gly Ile Asn Val Asn Ala Ala Pro Phe Gln
500 505 510
Ser Met Gln Thr Val Phe Asn Met Asn Ala Pro Val Pro Pro Ala Asn
515 520 525
Glu Pro Glu Thr Leu Lys Gln Gln Ser Gln Tyr Gln Ala Thr Tyr Asn
530 535 540
Gln Ser Phe Ser Ser Gln Pro His Gln Val Glu Gln Thr Glu Leu Gln
545 550 555 560
Gln Asp Gln Leu Gln Thr Val Val Gly Thr Tyr His Gly Ser Gln Asp
565 570 575
Gln Pro His Gln Val Pro Gly Asn His Gln Gln Pro Pro Gln Gln Asn
580 585 590
Thr Gly Phe Pro Arg Ser Ser Gln Pro Tyr Tyr Asn Ser Arg Gly Val
595 600 605
Ser Arg Gly Gly Ser Arg Gly Ala Arg Gly Leu Met Asn Gly Tyr Arg
610 615 620
Gly Pro Ala Asn Gly Phe Arg Gly Gly Tyr Asp Gly Tyr Arg Pro Ser
625 630 635 640
Phe Ser Asn Thr Pro Asn Ser Gly Tyr Ser Gln Ser Gln Phe Thr Ala
645 650 655
Pro Arg Asp Tyr Ser Gly Tyr Gln Arg Asp Gly Tyr Gln Gln Asn Phe
660 665 670
Lys Arg Gly Ser Gly Gln Ser Gly Pro Arg Gly Ala Pro Arg Gly Asn
675 680 685
Ile Leu Trp Trp
690
<210> 27
<211> 3508
<212> DNA
<213> 小鼠(Mus musculus)
<220>
<221> CDS
<222> (139)..(2217)
<400> 27
cccaccgcgc gcgcgcgtag ccgcctgccc gcccgcccgc tgcgcgtttt gtcccgcgtc 60
tctccccgtc cgtctcctga cttgctggtc ttgtccttcc ctcccgcttt tttcctctcc 120
tctcttctcg gtctaaag atg ccc tcg gcc acc agc cac agc gga agc ggc 171
Met Pro Ser Ala Thr Ser His Ser Gly Ser Gly
1 5 10
agc aaa tcg tcg gga ccg ccg ccg ccg tcc ggt tcc tcc ggg agt gag 219
Ser Lys Ser Ser Gly Pro Pro Pro Pro Ser Gly Ser Ser Gly Ser Glu
15 20 25
gcg gcg gcc ggg gca gct gcg ccg gct tct cag cat ccg gca acc ggc 267
Ala Ala Ala Gly Ala Ala Ala Pro Ala Ser Gln His Pro Ala Thr Gly
30 35 40
acc ggc gcc gtc cag acc gag gcc atg aag cag att ctc ggc gta atc 315
Thr Gly Ala Val Gln Thr Glu Ala Met Lys Gln Ile Leu Gly Val Ile
45 50 55
gac aag aaa ctt cgg aac ctg gag aag aaa aag ggt aaa ctt gat gat 363
Asp Lys Lys Leu Arg Asn Leu Glu Lys Lys Lys Gly Lys Leu Asp Asp
60 65 70 75
tac cag gaa cga atg aat aaa ggg gaa agg ctc aat caa gac cag ctg 411
Tyr Gln Glu Arg Met Asn Lys Gly Glu Arg Leu Asn Gln Asp Gln Leu
80 85 90
gat gcc gta tct aag tac cag gaa gtc aca aat aat ttg gag ttt gca 459
Asp Ala Val Ser Lys Tyr Gln Glu Val Thr Asn Asn Leu Glu Phe Ala
95 100 105
aag gaa tta cag agg agt ttc atg gca tta agt caa gat att cag aaa 507
Lys Glu Leu Gln Arg Ser Phe Met Ala Leu Ser Gln Asp Ile Gln Lys
110 115 120
aca ata aag aag aca gca cgt cgg gaa cag ctt atg aga gaa gaa gca 555
Thr Ile Lys Lys Thr Ala Arg Arg Glu Gln Leu Met Arg Glu Glu Ala
125 130 135
gaa cag aag cgc tta aaa act gta ctt gag tta cag tat gta ttg gat 603
Glu Gln Lys Arg Leu Lys Thr Val Leu Glu Leu Gln Tyr Val Leu Asp
140 145 150 155
aag ctg gga gat gat gat gtg aga aca gat ctg aaa caa ggt ttg agt 651
Lys Leu Gly Asp Asp Asp Val Arg Thr Asp Leu Lys Gln Gly Leu Ser
160 165 170
gga gtg cca ata ttg tct gag gag gag ttg tca ttg ctg gat gag ttc 699
Gly Val Pro Ile Leu Ser Glu Glu Glu Leu Ser Leu Leu Asp Glu Phe
175 180 185
tac aag ctc gta gat cct gag cgt gac atg agt tta agg tta aat gag 747
Tyr Lys Leu Val Asp Pro Glu Arg Asp Met Ser Leu Arg Leu Asn Glu
190 195 200
cag tat gaa cat gcc tca att cac ttg tgg gat ttg ctg gaa ggg aaa 795
Gln Tyr Glu His Ala Ser Ile His Leu Trp Asp Leu Leu Glu Gly Lys
205 210 215
gaa aag cct gtg tgt gga aca acc tat aaa gct cta aag gaa att gtt 843
Glu Lys Pro Val Cys Gly Thr Thr Tyr Lys Ala Leu Lys Glu Ile Val
220 225 230 235
gag cgt gtt ttc cag tca aac tac ttt gat agc act cac aat cat caa 891
Glu Arg Val Phe Gln Ser Asn Tyr Phe Asp Ser Thr His Asn His Gln
240 245 250
aat ggg ttg tgt gag gag gaa gag gcg gct tca gcg ccc aca gtg gag 939
Asn Gly Leu Cys Glu Glu Glu Glu Ala Ala Ser Ala Pro Thr Val Glu
255 260 265
gac cag gta gct gaa gct gaa cct gag cca gcg gaa gaa tac aca gag 987
Asp Gln Val Ala Glu Ala Glu Pro Glu Pro Ala Glu Glu Tyr Thr Glu
270 275 280
caa agt gag gtt gaa tca aca gag tat gtc aat agg cag ttc atg gca 1035
Gln Ser Glu Val Glu Ser Thr Glu Tyr Val Asn Arg Gln Phe Met Ala
285 290 295
gaa aca cag ttc agc agt ggt gag aag gag caa gtg gat gag tgg aca 1083
Glu Thr Gln Phe Ser Ser Gly Glu Lys Glu Gln Val Asp Glu Trp Thr
300 305 310 315
gtt gaa aca gtt gag gtt gta aac tca ctc cag cag caa cct cag gct 1131
Val Glu Thr Val Glu Val Val Asn Ser Leu Gln Gln Gln Pro Gln Ala
320 325 330
gcg tcc cct tca gtc cca gag ccc cac tct ttg act cca gtg gct cag 1179
Ala Ser Pro Ser Val Pro Glu Pro His Ser Leu Thr Pro Val Ala Gln
335 340 345
tca gat cca ctt gtg aga agg cag cgt gta caa gat ctt atg gca caa 1227
Ser Asp Pro Leu Val Arg Arg Gln Arg Val Gln Asp Leu Met Ala Gln
350 355 360
atg caa ggg ccc tat aat ttc ata cag gat tca atg ttg gat ttt gaa 1275
Met Gln Gly Pro Tyr Asn Phe Ile Gln Asp Ser Met Leu Asp Phe Glu
365 370 375
aat cag acg ctt gat cct gcc att gta tcc gca cag cct atg aac cct 1323
Asn Gln Thr Leu Asp Pro Ala Ile Val Ser Ala Gln Pro Met Asn Pro
380 385 390 395
acc cag aac atg gat atg cct cag ctg gtt tgc cct cag gtt cat tct 1371
Thr Gln Asn Met Asp Met Pro Gln Leu Val Cys Pro Gln Val His Ser
400 405 410
gaa tct aga ctt gcc caa tct aat caa gtt cct gta caa cca gaa gcc 1419
Glu Ser Arg Leu Ala Gln Ser Asn Gln Val Pro Val Gln Pro Glu Ala
415 420 425
aca cag gtt cct ttg gtt tca tcc aca agt gag ggg tat aca gca tct 1467
Thr Gln Val Pro Leu Val Ser Ser Thr Ser Glu Gly Tyr Thr Ala Ser
430 435 440
cag ccc ttg tac cag cca tct cat gct acg gag cag cgg ccg cag aaa 1515
Gln Pro Leu Tyr Gln Pro Ser His Ala Thr Glu Gln Arg Pro Gln Lys
445 450 455
gag cca atg gat cag att cag gca aca ata tct ttg aat aca gac cag 1563
Glu Pro Met Asp Gln Ile Gln Ala Thr Ile Ser Leu Asn Thr Asp Gln
460 465 470 475
act aca gca tcc tca tcc ctt cct gct gct tct cag cct caa gtg ttc 1611
Thr Thr Ala Ser Ser Ser Leu Pro Ala Ala Ser Gln Pro Gln Val Phe
480 485 490
cag gct ggg aca agt aaa cct ttg cac agc agt gga atc aat gta aat 1659
Gln Ala Gly Thr Ser Lys Pro Leu His Ser Ser Gly Ile Asn Val Asn
495 500 505
gca gct cca ttc cag tcc atg caa acg gtg ttc aat atg aat gct cca 1707
Ala Ala Pro Phe Gln Ser Met Gln Thr Val Phe Asn Met Asn Ala Pro
510 515 520
gtc cct cct gct aat gaa cca gaa acg tta aaa caa cag agt cag tac 1755
Val Pro Pro Ala Asn Glu Pro Glu Thr Leu Lys Gln Gln Ser Gln Tyr
525 530 535
cag gcc act tat aac cag agt ttt tcc agt cag cct cac caa gtg gaa 1803
Gln Ala Thr Tyr Asn Gln Ser Phe Ser Ser Gln Pro His Gln Val Glu
540 545 550 555
caa aca gag ctt caa caa gac caa ctg caa acg gtg gtt ggc act tac 1851
Gln Thr Glu Leu Gln Gln Asp Gln Leu Gln Thr Val Val Gly Thr Tyr
560 565 570
cat gga tcc cag gac cag cct cat caa gtg cct ggt aac cac cag caa 1899
His Gly Ser Gln Asp Gln Pro His Gln Val Pro Gly Asn His Gln Gln
575 580 585
ccc cca cag cag aac act ggc ttt cca cgt agc agt cag cct tat tac 1947
Pro Pro Gln Gln Asn Thr Gly Phe Pro Arg Ser Ser Gln Pro Tyr Tyr
590 595 600
aac agt cgt ggg gta tct cga gga ggg tct cgt ggt gcc aga ggc ttg 1995
Asn Ser Arg Gly Val Ser Arg Gly Gly Ser Arg Gly Ala Arg Gly Leu
605 610 615
atg aat gga tac agg ggc cct gcc aat gga ttt aga gga gga tat gat 2043
Met Asn Gly Tyr Arg Gly Pro Ala Asn Gly Phe Arg Gly Gly Tyr Asp
620 625 630 635
ggt tac cgc cct tca ttc tcg aac act cca aac agt ggt tat tca cag 2091
Gly Tyr Arg Pro Ser Phe Ser Asn Thr Pro Asn Ser Gly Tyr Ser Gln
640 645 650
tct cag ttc act gct ccc cgg gac tac tct ggt tac cag cgg gat gga 2139
Ser Gln Phe Thr Ala Pro Arg Asp Tyr Ser Gly Tyr Gln Arg Asp Gly
655 660 665
tat cag cag aat ttc aag cga ggc tct ggg cag agt gga cca cgg gga 2187
Tyr Gln Gln Asn Phe Lys Arg Gly Ser Gly Gln Ser Gly Pro Arg Gly
670 675 680
gcc cca cga ggt aat ata ttg tgg tgg tga tcctagctcc tatgtggagc 2237
Ala Pro Arg Gly Asn Ile Leu Trp Trp
685 690
ttctgttctg gccttggaag aactgttcat agtccgcatg taggttacat gttaggaata 2297
catttatctt ttccagactt gttgctaaag attaaatgaa atgctctgtt tctaaaattt 2357
catcttgaat ccaaatttta atttttgaat gactttccct gctgttgtct tcaaaatcag 2417
aacattttct ctgcctcaga aaagcgtttt tccaactgga aatttatttt tcaggtctta 2477
aaacctgcta aatgttttta ggaagtacct actgaaactt tttgtaagac atttttggaa 2537
cgagcttgaa catttatata aatttattac cctctttgat ttttgaaaca tgcatattat 2597
atttaggctg agaagccctt caaatggcca gataagccac agttttagct agagaaccat 2657
ttagaattga cataactaat ctaaacttga acacttttag gaccaatgtt agtgttctaa 2717
ataccaacat atttctgatg tttaaacaga tctcccaaat tcttaggacc ttgatgtcat 2777
taaaatttag aatgacaagc ttaagaggct ttagtttcat ttgtttttca agtaatgaaa 2837
aataatttct tacatgggca gatagttaat ttgttgaaca attacaggta gcatttcatg 2897
taatctgatg ttctaaatgg ttctcttatt gaaggaggtt aaagaattag gtttcttaca 2957
gtttttggct ggccatgaca tgtataaaat gtatattaag gaggaattat aaagtacttt 3017
aatttgaatg ctagtggcaa ttgatcatta agaaagtact ttaaagcaaa aggttaatgg 3077
gtcatctggg aaaaatactg aagtatcaaa ggtatttgca tgtgaatgtg ggttatgttc 3137
ttctatccca ccttgtagca tattctatga aagttgagtt aaatgatagc taaaatatct 3197
gtttcaacag catgtaaaaa gttattttaa ctgttacaag tcattataca attttgaatg 3257
ttctgtagtt tctttttaac agtttaggta caaaggtctg ttttcattct ggtgcttttt 3317
attaattttg atagtatgat gtcacttcct attgaaatgt aagctagcgt gtaccttaga 3377
atgtgagctc catgagagca ggtaccttgt ttgtcttcac tgctgtatct attcccaacg 3437
cctcatgaca gtgcctggca catagtaggc actcaataaa tacttgttga atgaatgaaa 3497
aaaaaaaaaa a 3508
<210> 28
<211> 692
<212> PRT
<213> 小鼠(Mus musculus)
<400> 28
Met Pro Ser Ala Thr Ser His Ser Gly Ser Gly Ser Lys Ser Ser Gly
1 5 10 15
Pro Pro Pro Pro Ser Gly Ser Ser Gly Ser Glu Ala Ala Ala Gly Ala
20 25 30
Ala Ala Pro Ala Ser Gln His Pro Ala Thr Gly Thr Gly Ala Val Gln
35 40 45
Thr Glu Ala Met Lys Gln Ile Leu Gly Val Ile Asp Lys Lys Leu Arg
50 55 60
Asn Leu Glu Lys Lys Lys Gly Lys Leu Asp Asp Tyr Gln Glu Arg Met
65 70 75 80
Asn Lys Gly Glu Arg Leu Asn Gln Asp Gln Leu Asp Ala Val Ser Lys
85 90 95
Tyr Gln Glu Val Thr Asn Asn Leu Glu Phe Ala Lys Glu Leu Gln Arg
100 105 110
Ser Phe Met Ala Leu Ser Gln Asp Ile Gln Lys Thr Ile Lys Lys Thr
115 120 125
Ala Arg Arg Glu Gln Leu Met Arg Glu Glu Ala Glu Gln Lys Arg Leu
130 135 140
Lys Thr Val Leu Glu Leu Gln Tyr Val Leu Asp Lys Leu Gly Asp Asp
145 150 155 160
Asp Val Arg Thr Asp Leu Lys Gln Gly Leu Ser Gly Val Pro Ile Leu
165 170 175
Ser Glu Glu Glu Leu Ser Leu Leu Asp Glu Phe Tyr Lys Leu Val Asp
180 185 190
Pro Glu Arg Asp Met Ser Leu Arg Leu Asn Glu Gln Tyr Glu His Ala
195 200 205
Ser Ile His Leu Trp Asp Leu Leu Glu Gly Lys Glu Lys Pro Val Cys
210 215 220
Gly Thr Thr Tyr Lys Ala Leu Lys Glu Ile Val Glu Arg Val Phe Gln
225 230 235 240
Ser Asn Tyr Phe Asp Ser Thr His Asn His Gln Asn Gly Leu Cys Glu
245 250 255
Glu Glu Glu Ala Ala Ser Ala Pro Thr Val Glu Asp Gln Val Ala Glu
260 265 270
Ala Glu Pro Glu Pro Ala Glu Glu Tyr Thr Glu Gln Ser Glu Val Glu
275 280 285
Ser Thr Glu Tyr Val Asn Arg Gln Phe Met Ala Glu Thr Gln Phe Ser
290 295 300
Ser Gly Glu Lys Glu Gln Val Asp Glu Trp Thr Val Glu Thr Val Glu
305 310 315 320
Val Val Asn Ser Leu Gln Gln Gln Pro Gln Ala Ala Ser Pro Ser Val
325 330 335
Pro Glu Pro His Ser Leu Thr Pro Val Ala Gln Ser Asp Pro Leu Val
340 345 350
Arg Arg Gln Arg Val Gln Asp Leu Met Ala Gln Met Gln Gly Pro Tyr
355 360 365
Asn Phe Ile Gln Asp Ser Met Leu Asp Phe Glu Asn Gln Thr Leu Asp
370 375 380
Pro Ala Ile Val Ser Ala Gln Pro Met Asn Pro Thr Gln Asn Met Asp
385 390 395 400
Met Pro Gln Leu Val Cys Pro Gln Val His Ser Glu Ser Arg Leu Ala
405 410 415
Gln Ser Asn Gln Val Pro Val Gln Pro Glu Ala Thr Gln Val Pro Leu
420 425 430
Val Ser Ser Thr Ser Glu Gly Tyr Thr Ala Ser Gln Pro Leu Tyr Gln
435 440 445
Pro Ser His Ala Thr Glu Gln Arg Pro Gln Lys Glu Pro Met Asp Gln
450 455 460
Ile Gln Ala Thr Ile Ser Leu Asn Thr Asp Gln Thr Thr Ala Ser Ser
465 470 475 480
Ser Leu Pro Ala Ala Ser Gln Pro Gln Val Phe Gln Ala Gly Thr Ser
485 490 495
Lys Pro Leu His Ser Ser Gly Ile Asn Val Asn Ala Ala Pro Phe Gln
500 505 510
Ser Met Gln Thr Val Phe Asn Met Asn Ala Pro Val Pro Pro Ala Asn
515 520 525
Glu Pro Glu Thr Leu Lys Gln Gln Ser Gln Tyr Gln Ala Thr Tyr Asn
530 535 540
Gln Ser Phe Ser Ser Gln Pro His Gln Val Glu Gln Thr Glu Leu Gln
545 550 555 560
Gln Asp Gln Leu Gln Thr Val Val Gly Thr Tyr His Gly Ser Gln Asp
565 570 575
Gln Pro His Gln Val Pro Gly Asn His Gln Gln Pro Pro Gln Gln Asn
580 585 590
Thr Gly Phe Pro Arg Ser Ser Gln Pro Tyr Tyr Asn Ser Arg Gly Val
595 600 605
Ser Arg Gly Gly Ser Arg Gly Ala Arg Gly Leu Met Asn Gly Tyr Arg
610 615 620
Gly Pro Ala Asn Gly Phe Arg Gly Gly Tyr Asp Gly Tyr Arg Pro Ser
625 630 635 640
Phe Ser Asn Thr Pro Asn Ser Gly Tyr Ser Gln Ser Gln Phe Thr Ala
645 650 655
Pro Arg Asp Tyr Ser Gly Tyr Gln Arg Asp Gly Tyr Gln Gln Asn Phe
660 665 670
Lys Arg Gly Ser Gly Gln Ser Gly Pro Arg Gly Ala Pro Arg Gly Asn
675 680 685
Ile Leu Trp Trp
690
<210> 29
<211> 2109
<212> DNA
<213> 鸡(Gallus gallus)
<220>
<221> CDS
<222> (1)..(2109)
<400> 29
atg ccc tcg gct acc aac ggc acc atg gcg agc agc agc ggg aag gcg 48
Met Pro Ser Ala Thr Asn Gly Thr Met Ala Ser Ser Ser Gly Lys Ala
1 5 10 15
ggc ccg ggc ggc aac gag cag gcc ccg gcg gcg gca gcg gcg gcc ccg 96
Gly Pro Gly Gly Asn Glu Gln Ala Pro Ala Ala Ala Ala Ala Ala Pro
20 25 30
cag gcg tcg ggc ggc agc atc acc tcg gtt cag acc gag gcc atg aag 144
Gln Ala Ser Gly Gly Ser Ile Thr Ser Val Gln Thr Glu Ala Met Lys
35 40 45
cag atc ttg gga gtg atc gac aaa aag ctc cgc aac ctc gag aag aaa 192
Gln Ile Leu Gly Val Ile Asp Lys Lys Leu Arg Asn Leu Glu Lys Lys
50 55 60
aag agc aaa ctt gac gat tac cag gaa cga atg aac aag ggg gaa cgt 240
Lys Ser Lys Leu Asp Asp Tyr Gln Glu Arg Met Asn Lys Gly Glu Arg
65 70 75 80
cta aat caa gat caa ctg gat gca gtg tca aaa tac cag gaa gtg aca 288
Leu Asn Gln Asp Gln Leu Asp Ala Val Ser Lys Tyr Gln Glu Val Thr
85 90 95
aat aac ctg gaa ttc gct aaa gaa ctg cag agg agc ttt atg gca ctg 336
Asn Asn Leu Glu Phe Ala Lys Glu Leu Gln Arg Ser Phe Met Ala Leu
100 105 110
agc caa gat atc cag aaa aca ata aaa aag acg gct cgc agg gag cag 384
Ser Gln Asp Ile Gln Lys Thr Ile Lys Lys Thr Ala Arg Arg Glu Gln
115 120 125
ctg atg aga gaa gag gct gag cag aag cgt tta aag act gtg cta gag 432
Leu Met Arg Glu Glu Ala Glu Gln Lys Arg Leu Lys Thr Val Leu Glu
130 135 140
ctg cag ttc att ttg gac aag ttg ggt gac gat gaa gtg cgc agt gac 480
Leu Gln Phe Ile Leu Asp Lys Leu Gly Asp Asp Glu Val Arg Ser Asp
145 150 155 160
ttg aaa caa gga tca aat gga gta ccg gta ctg aca gag gag gaa ctg 528
Leu Lys Gln Gly Ser Asn Gly Val Pro Val Leu Thr Glu Glu Glu Leu
165 170 175
aca atg ctg gat gaa ttt tac aag cta gtt tac cct gaa agg gac atg 576
Thr Met Leu Asp Glu Phe Tyr Lys Leu Val Tyr Pro Glu Arg Asp Met
180 185 190
aac atg agg ttg aat gag cag tat gag caa gca tct gtt cac ctg tgg 624
Asn Met Arg Leu Asn Glu Gln Tyr Glu Gln Ala Ser Val His Leu Trp
195 200 205
gac tta ctg gaa ggg aag gaa aaa ccc gtt tgt gga aca acc tat aaa 672
Asp Leu Leu Glu Gly Lys Glu Lys Pro Val Cys Gly Thr Thr Tyr Lys
210 215 220
gcc ctg aag gag gtt gtt gaa cgt att ctt caa act agt tac ttt gat 720
Ala Leu Lys Glu Val Val Glu Arg Ile Leu Gln Thr Ser Tyr Phe Asp
225 230 235 240
agc acc cat aac cat cag aac ggg tta tgt gag gaa gaa gag gca gca 768
Ser Thr His Asn His Gln Asn Gly Leu Cys Glu Glu Glu Glu Ala Ala
245 250 255
ccc aca cct gca gta gaa gac act gta gca gaa gct gag cct gat cca 816
Pro Thr Pro Ala Val Glu Asp Thr Val Ala Glu Ala Glu Pro Asp Pro
260 265 270
gca gaa gaa ttt act gaa cct act gaa gtt gaa tcg act gag tat gta 864
Ala Glu Glu Phe Thr Glu Pro Thr Glu Val Glu Ser Thr Glu Tyr Val
275 280 285
aac aga caa ttc atg gca gag act cag ttc agc agt agt gag aag gaa 912
Asn Arg Gln Phe Met Ala Glu Thr Gln Phe Ser Ser Ser Glu Lys Glu
290 295 300
cag gta gat gag tgg aca gtt gaa acg gtt gag gtt gta aat tca ctg 960
Gln Val Asp Glu Trp Thr Val Glu Thr Val Glu Val Val Asn Ser Leu
305 310 315 320
cag caa caa aca caa gct aca tct cct cca gtt cct gaa cct cat aca 1008
Gln Gln Gln Thr Gln Ala Thr Ser Pro Pro Val Pro Glu Pro His Thr
325 330 335
ctc act act gtg gct caa gca gat cct ctt gtt aga aga cag aga gta 1056
Leu Thr Thr Val Ala Gln Ala Asp Pro Leu Val Arg Arg Gln Arg Val
340 345 350
cag gac ctt atg gcc cag atg cag ggt cca tat aac ttc atg cag gac 1104
Gln Asp Leu Met Ala Gln Met Gln Gly Pro Tyr Asn Phe Met Gln Asp
355 360 365
tct atg ctg gag ttt gag aac cag aca ctt gat cct gcc att gta tct 1152
Ser Met Leu Glu Phe Glu Asn Gln Thr Leu Asp Pro Ala Ile Val Ser
370 375 380
gca cag ccc atg aat cca gca cag aat ttg gac atg ccg caa atg gtc 1200
Ala Gln Pro Met Asn Pro Ala Gln Asn Leu Asp Met Pro Gln Met Val
385 390 395 400
tgc cct cca gtt cat act gag tca aga ctt gcc cag cct aat caa gtt 1248
Cys Pro Pro Val His Thr Glu Ser Arg Leu Ala Gln Pro Asn Gln Val
405 410 415
cct gtg caa cca gaa gct acg cag gtt ccc ttg gtt tca tct aca agt 1296
Pro Val Gln Pro Glu Ala Thr Gln Val Pro Leu Val Ser Ser Thr Ser
420 425 430
gag gga tat aca gcc tcc cag ccc atg tat cag cct tct cat acc aca 1344
Glu Gly Tyr Thr Ala Ser Gln Pro Met Tyr Gln Pro Ser His Thr Thr
435 440 445
gag caa cgg cca cag aag gaa tcc att gac cag att cag gct tca atg 1392
Glu Gln Arg Pro Gln Lys Glu Ser Ile Asp Gln Ile Gln Ala Ser Met
450 455 460
tca ctg aat gca gac cag acc ccg tca tca tca tca ctt ccc act gca 1440
Ser Leu Asn Ala Asp Gln Thr Pro Ser Ser Ser Ser Leu Pro Thr Ala
465 470 475 480
tcc cag ccg caa gtt ttc caa gct gga tct agc aaa cct ttg cat agc 1488
Ser Gln Pro Gln Val Phe Gln Ala Gly Ser Ser Lys Pro Leu His Ser
485 490 495
agc gga atc aat gtt aat gca gct cca ttc caa tcc atg caa aca gta 1536
Ser Gly Ile Asn Val Asn Ala Ala Pro Phe Gln Ser Met Gln Thr Val
500 505 510
ttc aac atg aat gca cct gtt cct cct gtt aat gag cca gaa gcc ctt 1584
Phe Asn Met Asn Ala Pro Val Pro Pro Val Asn Glu Pro Glu Ala Leu
515 520 525
aag caa caa aat cag tac cag gcc agt tac aac cag agt ttc tcc aat 1632
Lys Gln Gln Asn Gln Tyr Gln Ala Ser Tyr Asn Gln Ser Phe Ser Asn
530 535 540
cag cca cac caa gta gaa caa tca gat ctt cag caa gaa cag ctc cag 1680
Gln Pro His Gln Val Glu Gln Ser Asp Leu Gln Gln Glu Gln Leu Gln
545 550 555 560
aca gtg gtt ggt act tac cat ggt tct ccg gac cag acc cat caa gtg 1728
Thr Val Val Gly Thr Tyr His Gly Ser Pro Asp Gln Thr His Gln Val
565 570 575
gca gga aac cac cag caa cct ccc cag cag aat act gga ttt cca cgc 1776
Ala Gly Asn His Gln Gln Pro Pro Gln Gln Asn Thr Gly Phe Pro Arg
580 585 590
aac agt cag cct tat tac aac agt cgg gga gtg tct cgt ggt gga tca 1824
Asn Ser Gln Pro Tyr Tyr Asn Ser Arg Gly Val Ser Arg Gly Gly Ser
595 600 605
cgt ggg act cgt gga ttg atg aat ggt tac agg gga cct gca aat gga 1872
Arg Gly Thr Arg Gly Leu Met Asn Gly Tyr Arg Gly Pro Ala Asn Gly
610 615 620
ttt aga gga gga tat gat ggc tac cgt cct tca ttt tcc aac act ccg 1920
Phe Arg Gly Gly Tyr Asp Gly Tyr Arg Pro Ser Phe Ser Asn Thr Pro
625 630 635 640
aac agt ggt tac acg cag ccc caa ttt aat gct cct cga gat tat tca 1968
Asn Ser Gly Tyr Thr Gln Pro Gln Phe Asn Ala Pro Arg Asp Tyr Ser
645 650 655
aac tac cag cgg gat gga tat cag cag aac ttc aaa cgt ggt tct gga 2016
Asn Tyr Gln Arg Asp Gly Tyr Gln Gln Asn Phe Lys Arg Gly Ser Gly
660 665 670
caa agt ggg cct cgg gga gct cct cga ggt cgt gga ggg ccc cca aga 2064
Gln Ser Gly Pro Arg Gly Ala Pro Arg Gly Arg Gly Gly Pro Pro Arg
675 680 685
cca aac aga ggg atg cct caa atg aac gct cag caa gtg aat taa 2109
Pro Asn Arg Gly Met Pro Gln Met Asn Ala Gln Gln Val Asn
690 695 700
<210> 30
<211> 702
<212> PRT
<213> 鸡(Gallus gallus)
<400> 30
Met Pro Ser Ala Thr Asn Gly Thr Met Ala Ser Ser Ser Gly Lys Ala
1 5 10 15
Gly Pro Gly Gly Asn Glu Gln Ala Pro Ala Ala Ala Ala Ala Ala Pro
20 25 30
Gln Ala Ser Gly Gly Ser Ile Thr Ser Val Gln Thr Glu Ala Met Lys
35 40 45
Gln Ile Leu Gly Val Ile Asp Lys Lys Leu Arg Asn Leu Glu Lys Lys
50 55 60
Lys Ser Lys Leu Asp Asp Tyr Gln Glu Arg Met Asn Lys Gly Glu Arg
65 70 75 80
Leu Asn Gln Asp Gln Leu Asp Ala Val Ser Lys Tyr Gln Glu Val Thr
85 90 95
Asn Asn Leu Glu Phe Ala Lys Glu Leu Gln Arg Ser Phe Met Ala Leu
100 105 110
Ser Gln Asp Ile Gln Lys Thr Ile Lys Lys Thr Ala Arg Arg Glu Gln
115 120 125
Leu Met Arg Glu Glu Ala Glu Gln Lys Arg Leu Lys Thr Val Leu Glu
130 135 140
Leu Gln Phe Ile Leu Asp Lys Leu Gly Asp Asp Glu Val Arg Ser Asp
145 150 155 160
Leu Lys Gln Gly Ser Asn Gly Val Pro Val Leu Thr Glu Glu Glu Leu
165 170 175
Thr Met Leu Asp Glu Phe Tyr Lys Leu Val Tyr Pro Glu Arg Asp Met
180 185 190
Asn Met Arg Leu Asn Glu Gln Tyr Glu Gln Ala Ser Val His Leu Trp
195 200 205
Asp Leu Leu Glu Gly Lys Glu Lys Pro Val Cys Gly Thr Thr Tyr Lys
210 215 220
Ala Leu Lys Glu Val Val Glu Arg Ile Leu Gln Thr Ser Tyr Phe Asp
225 230 235 240
Ser Thr His Asn His Gln Asn Gly Leu Cys Glu Glu Glu Glu Ala Ala
245 250 255
Pro Thr Pro Ala Val Glu Asp Thr Val Ala Glu Ala Glu Pro Asp Pro
260 265 270
Ala Glu Glu Phe Thr Glu Pro Thr Glu Val Glu Ser Thr Glu Tyr Val
275 280 285
Asn Arg Gln Phe Met Ala Glu Thr Gln Phe Ser Ser Ser Glu Lys Glu
290 295 300
Gln Val Asp Glu Trp Thr Val Glu Thr Val Glu Val Val Asn Ser Leu
305 310 315 320
Gln Gln Gln Thr Gln Ala Thr Ser Pro Pro Val Pro Glu Pro His Thr
325 330 335
Leu Thr Thr Val Ala Gln Ala Asp Pro Leu Val Arg Arg Gln Arg Val
340 345 350
Gln Asp Leu Met Ala Gln Met Gln Gly Pro Tyr Asn Phe Met Gln Asp
355 360 365
Ser Met Leu Glu Phe Glu Asn Gln Thr Leu Asp Pro Ala Ile Val Ser
370 375 380
Ala Gln Pro Met Asn Pro Ala Gln Asn Leu Asp Met Pro Gln Met Val
385 390 395 400
Cys Pro Pro Val His Thr Glu Ser Arg Leu Ala Gln Pro Asn Gln Val
405 410 415
Pro Val Gln Pro Glu Ala Thr Gln Val Pro Leu Val Ser Ser Thr Ser
420 425 430
Glu Gly Tyr Thr Ala Ser Gln Pro Met Tyr Gln Pro Ser His Thr Thr
435 440 445
Glu Gln Arg Pro Gln Lys Glu Ser Ile Asp Gln Ile Gln Ala Ser Met
450 455 460
Ser Leu Asn Ala Asp Gln Thr Pro Ser Ser Ser Ser Leu Pro Thr Ala
465 470 475 480
Ser Gln Pro Gln Val Phe Gln Ala Gly Ser Ser Lys Pro Leu His Ser
485 490 495
Ser Gly Ile Asn Val Asn Ala Ala Pro Phe Gln Ser Met Gln Thr Val
500 505 510
Phe Asn Met Asn Ala Pro Val Pro Pro Val Asn Glu Pro Glu Ala Leu
515 520 525
Lys Gln Gln Asn Gln Tyr Gln Ala Ser Tyr Asn Gln Ser Phe Ser Asn
530 535 540
Gln Pro His Gln Val Glu Gln Ser Asp Leu Gln Gln Glu Gln Leu Gln
545 550 555 560
Thr Val Val Gly Thr Tyr His Gly Ser Pro Asp Gln Thr His Gln Val
565 570 575
Ala Gly Asn His Gln Gln Pro Pro Gln Gln Asn Thr Gly Phe Pro Arg
580 585 590
Asn Ser Gln Pro Tyr Tyr Asn Ser Arg Gly Val Ser Arg Gly Gly Ser
595 600 605
Arg Gly Thr Arg Gly Leu Met Asn Gly Tyr Arg Gly Pro Ala Asn Gly
610 615 620
Phe Arg Gly Gly Tyr Asp Gly Tyr Arg Pro Ser Phe Ser Asn Thr Pro
625 630 635 640
Asn Ser Gly Tyr Thr Gln Pro Gln Phe Asn Ala Pro Arg Asp Tyr Ser
645 650 655
Asn Tyr Gln Arg Asp Gly Tyr Gln Gln Asn Phe Lys Arg Gly Ser Gly
660 665 670
Gln Ser Gly Pro Arg Gly Ala Pro Arg Gly Arg Gly Gly Pro Pro Arg
675 680 685
Pro Asn Arg Gly Met Pro Gln Met Asn Ala Gln Gln Val Asn
690 695 700
<210> 31
<211> 63
<212> PRT
<213> 人(Homo sapiens)
<400> 31
Glu Glu Tyr Thr Glu Gln Ser Glu Val Glu Ser Thr Glu Tyr Val Asn
1 5 10 15
Arg Gln Phe Met Ala Glu Thr Gln Phe Thr Ser Gly Glu Lys Glu Gln
20 25 30
Val Asp Glu Trp Thr Val Glu Thr Val Glu Val Val Asn Ser Leu Gln
35 40 45
Gln Gln Pro Gln Ala Ala Ser Pro Ser Val Pro Glu Pro His Ser
50 55 60
<210> 32
<211> 18
<212> PRT
<213> 人(Homo sapiens)
<400> 32
Val Phe Asn Met Asn Ala Pro Val Pro Pro Val Asn Glu Pro Glu Thr
1 5 10 15
Leu Lys
<210> 33
<211> 16
<212> PRT
<213> 人(Homo sapiens)
<400> 33
Ala Thr Gln Val Pro Leu Val Ser Ser Thr Ser Glu Gly Tyr Thr Ala
1 5 10 15
<210> 34
<211> 25
<212> PRT
<213> 人(Homo sapiens)
<400> 34
Gln Ile Leu Gly Val Ile Asp Lys Lys Leu Arg Asn Leu Glu Lys Lys
1 5 10 15
Lys Gly Lys Leu Asp Asp Tyr Gln Glu
20 25
<210> 35
<211> 23
<212> PRT
<213> 人(Homo sapiens)
<400> 35
Pro Arg Gly Arg Gly Gly Pro Pro Arg Pro Asn Arg Gly Met Pro Gln
1 5 10 15
Met Asn Thr Gln Gln Val Asn
20
<210> 36
<211> 5
<212> PRT
<213> 鸡(Gallus gallus)
<400> 36
Ser Tyr Gln Met Asn
1 5
<210> 37
<211> 17
<212> PRT
<213> 鸡(Gallus gallus)
<400> 37
Ala Ile Asn Lys Phe Gly Asn Ser Thr Gly His Gly Ala Ala Val Lys
1 5 10 15
Gly
<210> 38
<211> 19
<212> PRT
<213> 鸡(Gallus gallus)
<400> 38
His Ala Tyr Gly Tyr Cys Gly Ser Gly Thr Trp Cys Ala Ala Gly Glu
1 5 10 15
Ile Asp Ala
<210> 39
<211> 128
<212> PRT
<213> 鸡(Gallus gallus)
<400> 39
Ala Val Thr Leu Asp Glu Ser Gly Gly Gly Leu Gln Met Ser Arg Gly
1 5 10 15
Gly Leu Ser Leu Val Cys Lys Ala Ser Gly Phe Asp Phe Ser Ser Tyr
20 25 30
Gln Met Asn Trp Ile Arg Gln Ala Pro Gly Lys Gly Leu Glu Phe Val
35 40 45
Ala Ala Ile Asn Lys Phe Gly Asn Ser Thr Gly His Gly Ala Ala Val
50 55 60
Lys Gly Arg Val Thr Ile Ser Arg Asp Asn Gly Gln Ser Thr Val Arg
65 70 75 80
Leu Gln Leu Asn Asn Leu Arg Ala Glu Asp Thr Ala Ile Tyr Phe Cys
85 90 95
Thr Lys His Ala Tyr Gly Tyr Cys Gly Ser Gly Thr Trp Cys Ala Ala
100 105 110
Gly Glu Ile Asp Ala Trp Gly His Gly Thr Glu Val Ile Val Ser Ser
115 120 125
<210> 40
<211> 9
<212> PRT
<213> 鸡(Gallus gallus)
<400> 40
Ser Gly Gly Gly Ser Tyr Ser Tyr Gly
1 5
<210> 41
<211> 7
<212> PRT
<213> 鸡(Gallus gallus)
<400> 41
Asn Asn Lys Arg Pro Ser Asp
1 5
<210> 42
<211> 10
<212> PRT
<213> 鸡(Gallus gallus)
<400> 42
Ser Gly Asp Ser Thr Asp Thr Ala Val Phe
1 5 10
<210> 43
<211> 108
<212> PRT
<213> 鸡(Gallus gallus)
<400> 43
Gln Ala Ala Ser Thr Gln Pro Ser Ser Val Ser Ala Asn Pro Gly Glu
1 5 10 15
Thr Val Glu Ile Thr Cys Ser Gly Gly Gly Ser Tyr Ser Tyr Gly Trp
20 25 30
Phe Gln Gln Lys Ser Pro Gly Ser Ala Pro Val Thr Val Ile Tyr Tyr
35 40 45
Asn Asn Lys Arg Pro Ser Asp Ile Pro Ser Arg Phe Ser Gly Ser Lys
50 55 60
Ser Gly Ser Thr Gly Thr Leu Thr Ile Thr Gly Val Gln Ala Asp Asp
65 70 75 80
Glu Ala Val Tyr Tyr Cys Gly Ser Gly Asp Ser Thr Asp Thr Ala Val
85 90 95
Phe Gly Ala Gly Thr Thr Leu Thr Val Leu Gly Gln
100 105
<210> 44
<211> 5
<212> PRT
<213> 兔(Rabbit)
<400> 44
Ser His Ser Leu Gly
1 5
<210> 45
<211> 16
<212> PRT
<213> 兔(Rabbit)
<400> 45
Asp Ile Arg Ser Gly Gly Ser Ala Tyr Tyr Ala Asn Trp Ala Lys Gly
1 5 10 15
<210> 46
<211> 13
<212> PRT
<213> 兔(Rabbit)
<400> 46
Thr Asn Gly Pro Ser Asp Leu Thr Asn Arg Leu Asp Leu
1 5 10
<210> 47
<211> 121
<212> PRT
<213> 人(Homo sapiens)
<400> 47
Glu Gln Ser Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Leu Ser Ser His
20 25 30
Ser Leu Gly Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Asp Ile Arg Ser Gly Gly Ser Ala Tyr Tyr Ala Asn Trp Ala Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Thr
85 90 95
Arg Thr Asn Gly Pro Ser Asp Leu Thr Asn Arg Leu Asp Leu Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 48
<211> 13
<212> PRT
<213> 兔(Rabbit)
<400> 48
Gln Ala Ser Gln Ser Leu Tyr Asn Asn Glu Asn Leu Ala
1 5 10
<210> 49
<211> 7
<212> PRT
<213> 兔(Rabbit)
<400> 49
Gly Ala Ser Thr Leu Ala Ser
1 5
<210> 50
<211> 13
<212> PRT
<213> 兔(Rabbit)
<400> 50
Leu Gly Glu Phe Ser Cys Gly Ser Ala Asp Cys Phe Ala
1 5 10
<210> 51
<211> 112
<212> PRT
<213> 人(Homo sapiens)
<400> 51
Gln Val Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp
1 5 10 15
Arg Val Thr Ile Asn Cys Gln Ala Ser Gln Ser Leu Tyr Asn Asn Glu
20 25 30
Asn Leu Ala Trp Phe Gln Gln Lys Pro Gly Lys Val Pro Lys Arg Leu
35 40 45
Ile Tyr Gly Ala Ser Thr Leu Ala Ser Gly Val Ser Ser Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln
65 70 75 80
Cys Glu Asp Phe Ala Ile Tyr Tyr Cys Leu Gly Glu Phe Ser Cys Gly
85 90 95
Ser Ala Asp Cys Phe Ala Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105 110
<210> 52
<211> 4
<212> PRT
<213> 鸡(Gallus gallus)
<400> 52
Phe Asp Met Gly
1
<210> 53
<211> 17
<212> PRT
<213> 鸡(Gallus gallus)
<400> 53
Gln Ile Asn Asp Ala Gly Ser Arg Thr Trp Tyr Ala Thr Ala Val Lys
1 5 10 15
Gly
<210> 54
<211> 12
<212> PRT
<213> 鸡(Gallus gallus)
<400> 54
Gly Ser Gly Tyr Val Gly Ala Gly Ala Ile Asp Ala
1 5 10
<210> 55
<211> 120
<212> PRT
<213> 鸡(Gallus gallus)
<400> 55
Ala Val Thr Leu Asp Glu Ser Gly Gly Gly Leu Gln Thr Pro Gly Gly
1 5 10 15
Gly Leu Ser Leu Val Cys Lys Ala Ser Gly Phe Thr Phe Ser Ser Phe
20 25 30
Asp Met Gly Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Phe Val
35 40 45
Ala Gln Ile Asn Asp Ala Gly Ser Arg Thr Trp Tyr Ala Thr Ala Val
50 55 60
Lys Gly Arg Ala Thr Ile Ser Arg Asp Asn Gly Gln Thr Thr Val Arg
65 70 75 80
Leu Gln Leu Asn Asn Leu Arg Ala Glu Asp Thr Gly Thr Tyr Tyr Cys
85 90 95
Thr Arg Gly Ser Gly Tyr Val Gly Ala Gly Ala Ile Asp Ala Trp Gly
100 105 110
His Gly Thr Glu Val Ile Val Ser
115 120
<210> 56
<211> 8
<212> PRT
<213> 鸡(Gallus gallus)
<400> 56
Ser Gly Gly Ser Gly Tyr Tyr Gly
1 5
<210> 57
<211> 7
<212> PRT
<213> 鸡(Gallus gallus)
<400> 57
Asn Asp Lys Arg Pro Ser Asp
1 5
<210> 58
<211> 10
<212> PRT
<213> 鸡(Gallus gallus)
<400> 58
Arg Tyr Asp Ser Thr Asp Ser Gly Ile Phe
1 5 10
<210> 59
<211> 105
<212> PRT
<213> 鸡(Gallus gallus)
<400> 59
Ala Ala Leu Thr Gln Pro Ser Ser Val Ser Ala Asn Pro Gly Glu Thr
1 5 10 15
Val Lys Ile Thr Cys Ser Gly Gly Ser Gly Tyr Tyr Gly Trp Tyr Gln
20 25 30
Gln Gln Lys Ser Pro Gly Ser Ala Pro Val Thr Val Ile Tyr Gln Asn
35 40 45
Asp Lys Arg Pro Ser Asp Ile Pro Ser Arg Phe Ser Gly Ser Gly Ser
50 55 60
Gly Ser Thr Asn Thr Leu Thr Ile Thr Gly Val Gln Ala Glu Asp Glu
65 70 75 80
Ala Val Tyr Phe Cys Gly Arg Tyr Asp Ser Thr Asp Ser Gly Ile Phe
85 90 95
Gly Ala Gly Thr Thr Leu Thr Val Leu
100 105
<210> 60
<211> 6
<212> PRT
<213> 兔(Oryctolagus cuniculus)
<400> 60
Gly Ser Tyr Tyr Met Ser
1 5
<210> 61
<211> 17
<212> PRT
<213> 兔(Oryctolagus cuniculus)
<400> 61
Tyr Ile Tyr Ile Gly Asp Gly Val Thr Ala Tyr Ala Asn Trp Ala Lys
1 5 10 15
Gly
<210> 62
<211> 4
<212> PRT
<213> 兔(Oryctolagus cuniculus)
<400> 62
Gly Asn Lys Leu
1
<210> 63
<211> 112
<212> PRT
<213> 兔(Oryctolagus cuniculus)
<400> 63
Gln Ser Leu Glu Glu Ser Gly Gly Asp Leu Val Lys Pro Gly Ala Ser
1 5 10 15
Leu Thr Leu Thr Cys Thr Ala Ser Gly Phe Ser Phe Ser Gly Ser Tyr
20 25 30
Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Ala Tyr Ile Tyr Ile Gly Asp Gly Val Thr Ala Tyr Ala Asn Trp Ala
50 55 60
Lys Gly Arg Phe Thr Ile Ser Lys Ala Ser Ser Thr Thr Val Thr Leu
65 70 75 80
Gln Met Thr Ser Leu Thr Ala Ala Asp Thr Ala Thr Tyr Phe Cys Ala
85 90 95
Arg Gly Asn Lys Leu Trp Gly Pro Gly Thr Leu Val Thr Val Ser Ser
100 105 110
<210> 64
<211> 11
<212> PRT
<213> 兔(Oryctolagus cuniculus)
<400> 64
Gln Ala Ser Gln Ser Ile Ser Ser Tyr Leu Ala
1 5 10
<210> 65
<211> 7
<212> PRT
<213> 兔(Oryctolagus cuniculus)
<400> 65
Asp Ala Ser Asn Leu Asp Ser
1 5
<210> 66
<211> 14
<212> PRT
<213> 兔(Oryctolagus cuniculus)
<400> 66
Gln Cys Thr Ala Val Ser Ser Ala Thr Ile Tyr Gly Asn Ala
1 5 10
<210> 67
<211> 112
<212> PRT
<213> 兔(Oryctolagus cuniculus)
<400> 67
Asp Val Val Met Thr Gln Thr Pro Ala Ser Val Glu Ala Ala Val Gly
1 5 10 15
Gly Thr Val Thr Ile Lys Cys Gln Ala Ser Gln Ser Ile Ser Ser Tyr
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Arg Leu Ile
35 40 45
Tyr Asp Ala Ser Asn Leu Asp Ser Gly Val Pro Ser Arg Phe Lys Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Ile Thr Ile Ser Asp Leu Glu Cys
65 70 75 80
Ala Asp Ala Ala Thr Tyr Tyr Cys Gln Cys Thr Ala Val Ser Ser Ala
85 90 95
Thr Ile Tyr Gly Asn Ala Phe Gly Gly Gly Thr Glu Val Val Val Lys
100 105 110
<210> 68
<211> 127
<212> PRT
<213> 鸡(Gallus gallus)
<400> 68
Ala Val Thr Leu Asp Glu Ser Gly Gly Gly Leu Gln Thr Pro Gly Gly
1 5 10 15
Ala Leu Ser Leu Val Cys Lys Ala Ser Gly Phe Thr Phe Ser Gly Tyr
20 25 30
Asp Met Leu Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ala Gly Ile Gly Ser Thr Gly Gly Gly Thr Asp Tyr Gly Ala Ala Val
50 55 60
Lys Gly Arg Ala Thr Ile Ser Arg Asp Asn Gly Gln Ser Thr Val Arg
65 70 75 80
Leu Gln Leu Asn Asn Leu Arg Ala Glu Asp Thr Ala Thr Tyr Tyr Cys
85 90 95
Ala Lys Val Ala Gly Gly Cys Asn Ser Gly Tyr Cys Arg Asp Ser Pro
100 105 110
Gly Ser Ile Asp Ala Trp Gly His Gly Thr Glu Val Ile Val Ser
115 120 125
<210> 69
<211> 107
<212> PRT
<213> 鸡(Gallus gallus)
<400> 69
Ala Val Thr Gln Gln Pro Ala Ser Val Ser Ala Asn Pro Gly Glu Thr
1 5 10 15
Val Lys Ile Thr Cys Ser Gly Gly Gly Ser Arg Asn Tyr Tyr Gly Trp
20 25 30
Tyr Gln Gln Lys Ser Pro Gly Ser Val Pro Val Thr Val Ile Tyr Tyr
35 40 45
Asp Asp Gln Arg Pro Ser Asn Ile Pro Ser Arg Phe Ser Gly Ala Leu
50 55 60
Ser Gly Ser Thr Ser Thr Leu Thr Ile Thr Gly Val Gln Ala Asp Asp
65 70 75 80
Glu Ala Val Tyr Phe Cys Gly Ser Ala Asp Ser Asn Thr Tyr Glu Gly
85 90 95
Ser Phe Gly Ala Gly Thr Thr Leu Thr Val Leu
100 105
<210> 70
<211> 148
<212> PRT
<213> 小鼠(Mus musculus)
<400> 70
Met Glu Trp Ser Gly Val Phe Ile Phe Leu Leu Ser Gly Thr Ala Gly
1 5 10 15
Val Leu Ser Glu Val Gln Leu His Gln Phe Gly Ala Glu Leu Val Lys
20 25 30
Pro Gly Ala Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe
35 40 45
Thr Asp Tyr Asn Met Asp Trp Val Lys Gln Ser His Gly Lys Ser Leu
50 55 60
Glu Trp Ile Gly Asp Ile Asn Pro Asn Tyr Asp Ser Thr Ser Tyr Asn
65 70 75 80
Gln Lys Phe Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser
85 90 95
Thr Ala Tyr Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Ser Arg Ser Tyr Asp Tyr Glu Gly Phe Ala Tyr
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala Ala Lys Thr Thr Pro
130 135 140
Pro Ser Val Tyr
145
<210> 71
<211> 105
<212> PRT
<213> 小鼠(Mus musculus)
<400> 71
Gly Leu Phe Cys Ser Val Glu Arg Cys His Tyr Gln Leu Gln Ser Ser
1 5 10 15
Gln Asn Leu Leu Ser Ile Val Asn Arg Tyr His Tyr Met Ser Gly Asn
20 25 30
Pro Pro Lys Leu Leu Val Tyr Pro Ala Leu Leu Ile Tyr Glu Ala Ser
35 40 45
Ile Thr Lys Ser Cys Val Pro Asp Arg Phe Thr Arg Ser Gly Ser Gly
50 55 60
Thr Asn Phe Thr Leu Thr Ile Asn Phe Val His Ala Asp Asp Leu Ile
65 70 75 80
Phe Tyr Tyr Cys Gln His Asn Arg Gly Ser Phe Leu Pro Ser Ser Ser
85 90 95
Val Gln Val Pro Arg Arg Arg Ser Asn
100 105
<210> 72
<211> 109
<212> PRT
<213> 小鼠(Mus musculus)
<400> 72
Pro Arg Ala Ser Leu Gly Val Ser Glu Thr Leu Leu Cys Thr Ser Gly
1 5 10 15
Phe Thr Phe Thr Asp Tyr Tyr Met Ser Trp Val Arg Gln Pro Pro Gly
20 25 30
Lys Ala Leu Glu Trp Leu Gly Phe Ile Arg Asn Lys Ala Asn Gly Tyr
35 40 45
Thr Thr Glu Tyr Ser Ala Ser Val Lys Gly Arg Phe Thr Ile Ser Arg
50 55 60
Asp Asn Ser Gln Ser Ile Leu Tyr Leu Gln Met Asn Thr Leu Arg Ala
65 70 75 80
Glu Asp Ser Ala Thr Tyr Tyr Cys Ala Arg Ala Asn Trp Ala Phe Asp
85 90 95
Tyr Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Lys
100 105
<210> 73
<211> 94
<212> PRT
<213> 小鼠(Mus musculus)
<400> 73
Ser Gly Asp Arg Val Ser Leu Ser Cys Arg Ala Ser Gln Ser Ile Ser
1 5 10 15
Asn Tyr Leu His Trp Tyr Gln Gln Lys Ser His Glu Ser Pro Arg Leu
20 25 30
Leu Ile Lys Tyr Ala Ser Gln Ser Ile Ser Gly Ile Pro Ser Arg Phe
35 40 45
Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Ser Ile Asn Ser Val
50 55 60
Glu Thr Glu Asp Phe Gly Met Tyr Phe Cys Gln Gln Ser Asn Ser Trp
65 70 75 80
Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Gln
85 90
<210> 74
<211> 118
<212> PRT
<213> 小鼠(Mus musculus)
<400> 74
Ala Ala Glu Leu Val Arg Pro Gly Thr Ser Val Lys Val Ser Cys Lys
1 5 10 15
Ala Ser Gly Tyr Ala Phe Thr Asn Tyr Leu Ile Val Trp Ile Lys Gln
20 25 30
Arg Pro Gly Gln Gly Leu Glu Trp Ile Gly Val Ile Ser Pro Gly Ser
35 40 45
Gly Gly Thr Asn Tyr Asn Glu Lys Phe Lys Gly Lys Ala Ile Leu Thr
50 55 60
Ala Asp Lys Ser Ser Ser Thr Ala Tyr Met Gln Leu Ser Ser Leu Thr
65 70 75 80
Ser Asp Glu Phe Ala Val Tyr Phe Cys Ala Arg Glu Lys Ile Tyr Asp
85 90 95
Asp Tyr Tyr Glu Gly Tyr Phe Asp Val Trp Gly Ala Gly Pro Arg His
100 105 110
Leu Leu Ala Ser Leu Ser
115
<210> 75
<211> 107
<212> PRT
<213> 小鼠(Mus musculus)
<400> 75
Gly Thr Arg Cys Asp Ile Arg Leu Thr Gln Thr Thr Ser Ser Leu Ser
1 5 10 15
Ala Ser Leu Gly Asp Arg Val Thr Ile Ser Cys Ser Ala Ser Leu Gly
20 25 30
Ile Gly Asn Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Val
35 40 45
Lys Leu Leu Ile Tyr Tyr Thr Ser Asn Leu His Ser Gly Val Pro Ser
50 55 60
Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Ser
65 70 75 80
Asn Leu Glu Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln His Tyr Ser
85 90 95
Lys Leu Pro Leu Thr Phe Gly Ala Gly Pro Ser
100 105
<210> 76
<211> 113
<212> PRT
<213> 小鼠(Mus musculus)
<400> 76
Gly Ala Glu Leu Val Arg Ser Gly Ala Ser Val Lys Met Ser Cys Lys
1 5 10 15
Ala Ser Gly Tyr Ser Phe Thr Asp Tyr Asn Met Tyr Trp Val Lys Gln
20 25 30
Thr Pro Gly Gln Gly Leu Glu Trp Ile Gly Tyr Ile Tyr Pro Gly Asn
35 40 45
Gly Gly Thr Asn Tyr Asn Gln Lys Phe Lys Gly Lys Ala Thr Leu Thr
50 55 60
Ala Asp Thr Ser Ser Ser Thr Ala Tyr Met Gln Ile Ser Ser Leu Thr
65 70 75 80
Ser Glu Asp Ser Ala Val Tyr Phe Cys Ala Arg Asp Tyr Asp Asp Gly
85 90 95
Gly Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Thr Val Thr Val Ser
100 105 110
Ser
<210> 77
<211> 117
<212> PRT
<213> 小鼠(Mus musculus)
<400> 77
Leu Leu Leu Trp Leu Thr Gly Ala Arg Cys Asp Ile Gln Met Thr Gln
1 5 10 15
Ser Pro Ala Ser Leu Ser Ala Ser Val Gly Glu Thr Val Thr Ile Thr
20 25 30
Cys Arg Ala Ser Gly Asn Ile His Asn Tyr Leu Thr Trp Tyr Gln Gln
35 40 45
Lys Gln Gly Lys Ser Pro Gln Leu Leu Val Tyr Asn Ala Lys Thr Leu
50 55 60
Ala Asp Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Gln
65 70 75 80
Tyr Ser Leu Lys Ile Asn Arg Leu Gln Pro Glu Asp Phe Gly Ser Tyr
85 90 95
Tyr Cys Gln His Phe Trp Asn Ile Pro Trp Thr Phe Gly Gly Gly Thr
100 105 110
Lys Leu Asn Ser Arg
115
<210> 78
<211> 114
<212> PRT
<213> 小鼠(Mus musculus)
<400> 78
Asp Ala Glu Leu Val Lys Pro Gly Ala Ser Val Lys Ile Ser Cys Lys
1 5 10 15
Ala Ser Gly Tyr Thr Phe Thr Asp His Ser Ile His Trp Val Gln Gln
20 25 30
Lys Pro Glu Gln Gly Leu Glu Trp Ile Gly Tyr Ile Ser Pro Gly Asn
35 40 45
Gly Asn Ile Lys Tyr Asn Glu Lys Phe Lys Gly Lys Ala Thr Leu Thr
50 55 60
Ala Asp Lys Ser Ser Ser Thr Ala Tyr Met Gln Leu Asn Ser Leu Thr
65 70 75 80
Ser Glu Asp Ser Ala Val Tyr Phe Cys Lys Arg Ser Leu Gly Arg Gly
85 90 95
Gly Pro Tyr Tyr Phe Asp Tyr Trp Gly Gln Gly Thr Thr Val Thr Val
100 105 110
Ser Ser
<210> 79
<211> 108
<212> PRT
<213> 小鼠(Mus musculus)
<400> 79
Asp Ile Val Leu Thr Gln Ala Ala Pro Ser Leu Pro Val Thr Pro Gly
1 5 10 15
Glu Ser Val Ser Ile Ser Cys Arg Ser Ser Lys Ser Leu Leu His Ser
20 25 30
Asn Gly Asn Thr Tyr Leu Tyr Trp Phe Leu Gln Arg Pro Gly Gln Ser
35 40 45
Pro Gln Leu Leu Ile Tyr Arg Met Ser Asn Leu Ala Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Ala Phe Thr Leu Arg Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln His
85 90 95
Arg Glu Tyr Pro Val Thr Phe Gly Ser Gly Pro Asn
100 105
<210> 80
<211> 111
<212> PRT
<213> 小鼠(Mus musculus)
<400> 80
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Met Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Ile Ser Cys Lys Ala Thr Gly Tyr Thr Phe Ser Ser Tyr
20 25 30
Trp Ile Glu Trp Val Lys Gln Arg Pro Gly His Gly Leu Glu Trp Ile
35 40 45
Gly Glu Ile Leu Pro Gly Ser Gly Ser Thr Asn Tyr Asn Glu Lys Phe
50 55 60
Lys Gly Lys Ala Thr Phe Thr Ala Asp Thr Ser Ser Asn Thr Ala Tyr
65 70 75 80
Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Ser Tyr Tyr Trp Tyr Phe Asp Val Trp Ala Gln Asp His Val
100 105 110
<210> 81
<211> 109
<212> PRT
<213> 小鼠(Mus musculus)
<400> 81
Ile Val Met Thr Gln Ala Ala Phe Ser Asn Pro Val Thr Leu Gly Thr
1 5 10 15
Ser Ala Ser Ile Ser Cys Arg Ser Ser Lys Asn Leu Leu His Ser Asn
20 25 30
Gly Ile Thr Tyr Leu Tyr Trp Tyr Leu Gln Arg Pro Gly Gln Ser Pro
35 40 45
Gln Leu Leu Ile Tyr Arg Val Ser Asn Leu Ala Ser Gly Val Pro Asn
50 55 60
Arg Phe Ser Gly Ser Glu Ser Gly Thr Asp Phe Thr Leu Arg Ile Ser
65 70 75 80
Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Ala Gln Leu Leu
85 90 95
Glu Leu Pro Tyr Thr Ser Glu Gly Thr Lys Arg Trp Glu
100 105
<210> 82
<211> 109
<212> PRT
<213> 小鼠(Mus musculus)
<400> 82
Gly Gly Gly Leu Val Lys Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala
1 5 10 15
Ala Ser Gly Phe Ala Phe Ser Ser Tyr Asp Met Ser Trp Ile Arg Gln
20 25 30
Thr Pro Glu Lys Arg Leu Glu Trp Val Ala Tyr Ile Ser Ser Gly Ala
35 40 45
Gly Ser Thr Tyr Tyr Pro Asp Thr Val Lys Gly Arg Phe Thr Val Ser
50 55 60
Arg Asp Asn Ala Lys Asn Thr Leu Tyr Leu Gln Met Ser Ser Leu Lys
65 70 75 80
Ser Glu Asp Thr Ala Met Tyr Tyr Cys Ala Arg His Phe Tyr Arg Phe
85 90 95
Asp Tyr Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser
100 105
<210> 83
<211> 113
<212> PRT
<213> 小鼠(Mus musculus)
<400> 83
Leu Leu Leu Cys Val Ser Gly Ala Pro Gly Ser Ile Val Met Thr Gln
1 5 10 15
Thr Pro Lys Phe Leu Leu Val Ser Ala Gly Asp Arg Ile Thr Ile Thr
20 25 30
Cys Lys Ala Ser Gln Ser Val Ser Asn Asp Val Ala Trp Tyr Gln Gln
35 40 45
Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile Tyr Tyr Ala Ser Asn Arg
50 55 60
Tyr Thr Gly Val Pro Asp Arg Phe Thr Gly Ser Gly Tyr Gly Thr Asp
65 70 75 80
Phe Thr Phe Thr Ile Ser Thr Val Gln Ala Glu Asp Leu Ala Val Tyr
85 90 95
Phe Cys Gln Gln Asp Asp Arg Phe Pro Leu Thr Phe Gly Ala Gly Pro
100 105 110
Ser
<210> 84
<211> 112
<212> PRT
<213> 小鼠(Mus musculus)
<400> 84
Gln Ile Gln Leu Val Gln Ser Gly Pro Glu Leu Lys Lys Pro Gly Glu
1 5 10 15
Thr Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr
20 25 30
Gly Met Asn Trp Val Lys Gln Ala Pro Gly Lys Gly Leu Lys Trp Met
35 40 45
Gly Trp Ile Asn Thr Tyr Thr Gly Glu Pro Thr Tyr Ala Asp Asp Phe
50 55 60
Lys Gly Arg Phe Ala Phe Ser Leu Glu Thr Ser Ala Ser Thr Ala Tyr
65 70 75 80
Leu Gln Ile Asn Asn Leu Lys Asn Glu Asp Thr Ala Thr Tyr Phe Cys
85 90 95
Ala Thr Gly Ala Trp Phe Ala Tyr Trp Ala Lys Asp Ser Ser Arg His
100 105 110
<210> 85
<211> 107
<212> PRT
<213> 小鼠(Mus musculus)
<400> 85
Gly Val Glu Gly Asp Ile Val Met Thr Gln Ser His Lys Phe Met Ser
1 5 10 15
Thr Ser Val Gly Asp Arg Val Ser Ile Thr Cys Lys Ala Ser Gln Asp
20 25 30
Val Gly Thr Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro
35 40 45
Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Asp
50 55 60
Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser
65 70 75 80
Asn Val Gln Ser Glu Asp Leu Ala Asp Tyr Phe Cys Gln Gln Tyr Ser
85 90 95
Ser Tyr Pro Leu Thr Phe Gly Ala Gly Pro Ser
100 105
<210> 86
<211> 118
<212> PRT
<213> 小鼠(Mus musculus)
<400> 86
Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Met Lys Val Ser Cys Val
1 5 10 15
Ala Ser Gly Phe Ser Phe Ile Asp Phe Trp Met Asn Trp Val Arg Gln
20 25 30
Ser Pro Glu Lys Gly Leu Glu Trp Val Ala Glu Ile Arg Leu Lys Ser
35 40 45
Asn Asn Tyr Ala Thr His Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr
50 55 60
Ile Ser Arg Asp Asp Ser Lys Ser Ser Val Tyr Leu Gln Met Asn Asn
65 70 75 80
Leu Arg Pro Glu Asp Thr Gly Ile Tyr Tyr Cys Thr Ser Leu Phe Tyr
85 90 95
Tyr Tyr Asp Gly Thr Ser Gly Phe Ala Tyr Trp Gly Gln Gly Thr Thr
100 105 110
Val Thr Val Leu Leu Lys
115
<210> 87
<211> 109
<212> PRT
<213> 小鼠(Mus musculus)
<400> 87
Asp Ile Val Met Thr Gln Ser Pro Ser Ser Leu Thr Val Thr Ala Gly
1 5 10 15
Glu Lys Val Thr Met His Cys Lys Ser Ser Gln Ser Leu Leu Asn Ser
20 25 30
Gly Asp Gln Lys Asn Tyr Leu Thr Trp Tyr Gln Gln Lys Pro Gly Gln
35 40 45
Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val
50 55 60
Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
65 70 75 80
Ile Ser Ser Val Gln Ala Glu Asp Leu Ala Val Tyr Tyr Cys Gln Asn
85 90 95
Asp Tyr Asp Tyr Pro Leu Thr Phe Gly Ala Gly Pro Ser
100 105
<210> 88
<211> 148
<212> PRT
<213> 小鼠(Mus musculus)
<400> 88
Met Glu Trp Ser Gly Val Phe Ile Phe Leu Leu Ser Gly Thr Ala Gly
1 5 10 15
Val Leu Ser Glu Val Gln Leu His Gln Phe Gly Ala Glu Leu Val Lys
20 25 30
Pro Gly Ala Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe
35 40 45
Thr Asp Tyr Asn Met Asp Trp Val Lys Gln Ser His Gly Lys Ser Leu
50 55 60
Glu Trp Ile Gly Asp Ile Asn Pro Asn Tyr Asp Ser Thr Ser Tyr Asn
65 70 75 80
Gln Lys Phe Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser
85 90 95
Thr Ala Tyr Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Ser Arg Ser Tyr Asp Tyr Glu Gly Phe Ala Tyr
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala Ala Lys Thr Thr Pro
130 135 140
Pro Ser Val Tyr
145
<210> 89
<211> 139
<212> PRT
<213> 小鼠(Mus musculus)
<400> 89
Met Ser Val Leu Thr Gln Val Leu Gly Leu Leu Leu Leu Trp Leu Thr
1 5 10 15
Gly Ala Arg Cys Asp Ile Gln Met Thr Gln Ser Pro Ala Ser Leu Ser
20 25 30
Ala Ser Val Gly Glu Thr Val Thr Ile Thr Cys Arg Ala Ser Gly Asn
35 40 45
Ile His Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Gln Gly Lys Ser Pro
50 55 60
Gln Leu Leu Val Tyr Asn Ala Lys Thr Leu Ala Asp Gly Val Pro Ser
65 70 75 80
Arg Phe Ser Gly Ser Gly Ser Gly Thr Gln Tyr Ser Leu Lys Ile Asn
85 90 95
Ser Leu Gln Pro Glu Asp Phe Gly Ser Tyr Tyr Cys Gln His Phe Trp
100 105 110
Ser Thr Leu Thr Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys Arg Ala
115 120 125
Asp Ala Ala Pro Thr Val Ser Asn Pro Tyr Asp
130 135
<210> 90
<211> 100
<212> PRT
<213> 小鼠(Mus musculus)
<400> 90
Asp Ile Leu Gln Ala Ser Gly Tyr Ser Phe Thr Gly Tyr Thr Met Asn
1 5 10 15
Trp Val Lys Gln Ser His Gly Lys Asn Leu Glu Trp Ile Gly Leu Ile
20 25 30
Asn Pro Tyr Asn Gly Gly Thr Ser Tyr Asn Gln Lys Phe Lys Gly Lys
35 40 45
Ala Thr Leu Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr Met Glu Leu
50 55 60
Leu Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys Ala Arg Trp
65 70 75 80
Gly Val Trp Ser Ala Met Asp Tyr Trp Gly Gln Gly Thr Thr Val Thr
85 90 95
Val Ser Ser Lys
100
<210> 91
<211> 90
<212> PRT
<213> 小鼠(Mus musculus)
<400> 91
Asp Arg Val Ser Ile Thr Cys Lys Ala Ser Gln Asn Val Arg Thr Ala
1 5 10 15
Val Ala Trp Tyr Gln Gln Lys Pro Arg Gln Ser Pro Lys Ala Leu Ile
20 25 30
Tyr Leu Ala Ser Asn Arg Asp Thr Gly Leu Pro Asp Arg Phe Pro Gly
35 40 45
Arg Gly Ser Gly Thr Asp Phe Thr Leu Asn Ile Thr Asn Val Gln Ser
50 55 60
Glu Asp Leu Glu Asp Tyr Phe Cys Leu Gln His Cys Asn Tyr Pro Asn
65 70 75 80
Glu Phe Arg Gly Cys Thr Lys Val Pro Ile
85 90
<210> 92
<211> 116
<212> PRT
<213> 小鼠(Mus musculus)
<400> 92
Leu Gln Glu Ser Gly Ala Glu Leu Ala Arg Pro Gly Ala Ser Val Lys
1 5 10 15
Leu Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr Trp Met Gln
20 25 30
Trp Val Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile Gly Ala Ile
35 40 45
Tyr Pro Gly Asp Gly Asp Thr Arg Tyr Thr Gln Lys Phe Lys Gly Lys
50 55 60
Ala Thr Leu Thr Ala Asp Lys Ser Ser Ser Thr Ala Tyr Met Gln Leu
65 70 75 80
Ser Ser Leu Ala Ser Glu Asp Ser Ala Val Tyr Tyr Cys Ala Arg Gly
85 90 95
Glu Tyr Gly Asn Tyr Phe Ala Tyr Trp Gly Gln Gly Thr Thr Val Thr
100 105 110
Val Ser Ser Asn
115
<210> 93
<211> 100
<212> PRT
<213> 小鼠(Mus musculus)
<400> 93
Thr Ser Asp Ala Ser Leu Gly Glu Arg Val Thr Ile Thr Cys Lys Ala
1 5 10 15
Ser Gln Asp Ile Asn Ser Tyr Leu Ser Trp Phe Gln Gln Lys Pro Gly
20 25 30
Lys Ser Pro Lys Thr Leu Ile Tyr Arg Ala Asn Arg Leu Val Asp Gly
35 40 45
Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Gln Asp Tyr Ser Leu
50 55 60
Thr Ile Ser Ser Leu Glu Tyr Glu Asp Met Gly Ile Tyr Tyr Cys Leu
65 70 75 80
Gln Tyr Asp Glu Phe Pro Leu Thr Phe Gly Gly Gly Thr Lys Leu Glu
85 90 95
Ile Lys Gln Lys
100
<210> 94
<211> 108
<212> PRT
<213> 小鼠(Mus musculus)
<400> 94
Ala Trp Leu Ser Gln Leu Ser Cys Thr Ala Ser Gly Phe Asn Ile Lys
1 5 10 15
Asp Thr Tyr Met His Trp Val Lys Gln Arg Pro Glu Gln Gly Leu Glu
20 25 30
Trp Ile Gly Arg Ile Asp Pro Ala Asn Gly Asn Thr Lys Tyr Asp Pro
35 40 45
Lys Phe Gln Gly Lys Ala Thr Ile Thr Ala Asp Thr Ser Ser Asn Thr
50 55 60
Ala Tyr Leu Gln Leu Ser Ser Leu Thr Ser Glu Asp Thr Ala Val Tyr
65 70 75 80
Tyr Cys Ala Arg Pro Ile His Tyr Tyr Tyr Gly Ser Ser Leu Ala Tyr
85 90 95
Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Lys
100 105
<210> 95
<211> 104
<212> PRT
<213> 小鼠(Mus musculus)
<400> 95
Glu Phe His Ala Val Ser Leu Gly Gln Arg Ala Thr Ile Ser Cys Arg
1 5 10 15
Ala Ser Glu Ser Val Asp Ser Tyr Gly Asn Ser Phe Met His Trp Tyr
20 25 30
Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Arg Ala Ser
35 40 45
Asn Leu Glu Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Arg
50 55 60
Thr Asp Phe Thr Leu Thr Ile Asn Pro Val Glu Ala Asp Asp Val Ala
65 70 75 80
Thr Tyr Tyr Cys Gln Gln Ser Asn Glu Asp Pro Gly Arg Ser Glu Val
85 90 95
Val Pro Ser Trp Arg Ser Asn Lys
100
<210> 96
<211> 109
<212> PRT
<213> 小鼠(Mus musculus)
<400> 96
Pro Arg Ala Ser Leu Gly Val Ser Glu Thr Leu Leu Cys Thr Ser Gly
1 5 10 15
Phe Thr Phe Thr Asp Tyr Tyr Met Ser Trp Val Arg Gln Pro Pro Gly
20 25 30
Lys Ala Leu Glu Trp Leu Gly Phe Ile Arg Asn Lys Ala Asn Gly Tyr
35 40 45
Thr Thr Glu Tyr Ser Ala Ser Val Lys Gly Arg Phe Thr Ile Ser Arg
50 55 60
Asp Asn Ser Gln Ser Ile Leu Tyr Leu Gln Met Asn Thr Leu Arg Ala
65 70 75 80
Glu Asp Ser Ala Thr Tyr Tyr Cys Ala Arg Ala Asn Trp Ala Phe Asp
85 90 95
Tyr Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Lys
100 105
<210> 97
<211> 94
<212> PRT
<213> 小鼠(Mus musculus)
<400> 97
Ser Gly Asp Arg Val Ser Leu Ser Cys Arg Ala Ser Gln Ser Ile Ser
1 5 10 15
Asn Tyr Leu His Trp Tyr Gln Gln Lys Ser His Glu Ser Pro Arg Leu
20 25 30
Leu Ile Lys Tyr Ala Ser Gln Ser Ile Ser Gly Ile Pro Ser Arg Phe
35 40 45
Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Ser Ile Asn Ser Val
50 55 60
Glu Thr Glu Asp Phe Gly Met Tyr Phe Cys Gln Gln Ser Asn Ser Trp
65 70 75 80
Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Gln
85 90
<210> 98
<211> 111
<212> PRT
<213> 小鼠(Mus musculus)
<400> 98
Pro Ala Cys Leu Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Thr Ser
1 5 10 15
Gly Phe Thr Phe Thr Asp Tyr Tyr Met Ser Trp Val Arg Gln Pro Pro
20 25 30
Gly Lys Ala Leu Glu Trp Leu Gly Phe Ile Arg Asn Lys Ala Asn Gly
35 40 45
Tyr Thr Thr Glu Tyr Ser Ala Ser Val Lys Gly Arg Phe Thr Ile Ser
50 55 60
Arg Asp Asn Ser Gln Ser Ile Leu Tyr Leu Gln Met Asn Thr Leu Arg
65 70 75 80
Ala Glu Asp Ser Ala Thr Tyr Tyr Cys Ala Arg Ala Pro Leu Leu Tyr
85 90 95
Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Thr Val Thr Val Ser
100 105 110
<210> 99
<211> 102
<212> PRT
<213> 小鼠(Mus musculus)
<400> 99
Arg Leu Pro Phe Tyr Ser Leu Glu Gln Arg Ala Thr Ile Ser Tyr Arg
1 5 10 15
Ala Ser Lys Asn Val Ser Thr Ser Gly Tyr Ser Tyr Met His Trp Asn
20 25 30
Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Leu Val Ser
35 40 45
Asn Leu Glu Ser Gly Val Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly
50 55 60
Thr Asp Phe Thr Leu Asn Ile His Pro Val Glu Glu Glu Asp Ala Ala
65 70 75 80
Thr Tyr Tyr Cys Gln His Ile Arg Glu Leu Thr Arg Ser Glu Leu Val
85 90 95
Pro Ser Trp Lys Ser Asn
100
<210> 100
<211> 101
<212> PRT
<213> 小鼠(Mus musculus)
<400> 100
Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr Trp Met His
1 5 10 15
Trp Val Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile Gly Met Ile
20 25 30
Asp Pro Ser Asn Ser Glu Thr Arg Leu Asn Gln Lys Phe Lys Asp Lys
35 40 45
Ala Thr Leu Asn Val Asp Lys Ser Ser Asn Thr Ala Tyr Met Gln Leu
50 55 60
Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys Ala Arg Gly
65 70 75 80
Leu Arg His Tyr Trp Tyr Phe Asp Val Trp Gly Gln Gly Thr Thr Val
85 90 95
Thr Val Ser Ser Lys
100
<210> 101
<211> 99
<212> PRT
<213> 小鼠(Mus musculus)
<400> 101
Thr Ile Leu Trp Arg Glu Gly Pro Phe Ser Tyr Arg Ala Ser Lys Ser
1 5 10 15
Val Ser Thr Ser Gly Tyr Ser Tyr Met His Trp Asn Gln Gln Lys Pro
20 25 30
Gly Gln Pro Pro Arg Leu Leu Ile Tyr Leu Val Ser Asn Leu Glu Ser
35 40 45
Gly Val Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr
50 55 60
Leu Asn Ile His Pro Val Glu Glu Glu Asp Ala Ala Thr Tyr Tyr Cys
65 70 75 80
Gln His Ile Arg Glu Leu Thr Arg Ser Glu Glu Val Pro Ser Trp Arg
85 90 95
Ser Asn Lys
<210> 102
<211> 110
<212> PRT
<213> 小鼠(Mus musculus)
<400> 102
Gly Gly Gly Leu Val Lys Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala
1 5 10 15
Ala Ser Gly Phe Thr Phe Ser Ser Tyr Gly Met Ser Trp Val Arg Gln
20 25 30
Thr Pro Glu Lys Arg Leu Glu Trp Val Ala Thr Ile Ser Ser Gly Gly
35 40 45
Ser Tyr Thr Tyr Tyr Pro Asp Ser Val Lys Gly Arg Phe Thr Ile Ser
50 55 60
Arg Asp Asn Ala Lys Asn Thr Leu Tyr Leu Gln Met Ser Ser Leu Arg
65 70 75 80
Ser Glu Asp Thr Ala Met Tyr Tyr Cys Ala Ser Leu Ala Ser Tyr Tyr
85 90 95
Phe Asp Tyr Trp Gly Gln Gly Thr Thr Leu Thr Val Ser Ser
100 105 110
<210> 103
<211> 113
<212> PRT
<213> 小鼠(Mus musculus)
<400> 103
Gly Ala Arg Cys Asp Val Gln Met Ile Gln Ser Pro Ser Ser Leu Ser
1 5 10 15
Ala Ser Leu Gly Asp Ile Val Thr Met Thr Cys Gln Ala Ser Gln Gly
20 25 30
Thr Ser Ile Asn Leu Asn Trp Phe Gln Gln Lys Pro Gly Lys Ala Pro
35 40 45
Lys Leu Leu Ile Tyr Gly Ala Ser Ser Leu Glu Asp Gly Val Pro Ser
50 55 60
Arg Phe Ser Gly Ser Cys Phe Gly Thr Asp Phe Thr Leu Thr Ile Ser
65 70 75 80
Ser Leu Glu Asp Glu Asp Met Ala Thr Tyr Phe Cys Leu Gln His Ser
85 90 95
Tyr Leu Pro Pro Leu Thr Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys
100 105 110
Arg
<210> 104
<211> 111
<212> PRT
<213> 小鼠(Mus musculus)
<400> 104
Gly Pro Gly Leu Val Gln Pro Ser Gln Ser Leu Ser Ile Thr Cys Thr
1 5 10 15
Val Ser Gly Phe Ser Leu Thr Thr Tyr Asp Leu His Trp Val Arg Gln
20 25 30
Ser Pro Gly Lys Gly Leu Glu Trp Leu Gly Val Ile Trp Ser Gly Gly
35 40 45
Ser Thr Asp Tyr Asn Ala Ala Phe Ile Ser Arg Leu Ser Ile Ser Lys
50 55 60
Asp Asn Ser Lys Ser Gln Val Phe Phe Lys Met Asn Ser Leu Gln Ala
65 70 75 80
Asn Asp Thr Ala Ile Tyr Tyr Cys Ala Arg Asn Tyr Gly Tyr Ser Ala
85 90 95
Trp Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala
100 105 110
<210> 105
<211> 118
<212> PRT
<213> 小鼠(Mus musculus)
<400> 105
Pro Ala Ser Ser Ser Asp Val Leu Met Thr Gln Thr Pro Leu Ser Leu
1 5 10 15
Pro Val Ser Leu Gly Asp Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln
20 25 30
Ser Ile Val His Ser Asn Gly Asn Thr Tyr Leu Glu Trp Tyr Leu Gln
35 40 45
Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile Tyr Lys Val Ser Asn Arg
50 55 60
Phe Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp
65 70 75 80
Phe Thr Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr
85 90 95
Tyr Cys Phe Gln Gly Ser His Val Pro Leu Thr Phe Gly Ala Gly Thr
100 105 110
Lys Leu Glu Leu Lys Arg
115
<210> 106
<211> 114
<212> PRT
<213> 小鼠(Mus musculus)
<400> 106
Gly Phe Glu Leu Lys Lys Pro Gly Glu Thr Val Lys Ile Ser Cys Lys
1 5 10 15
Ala Ser Gly Tyr Thr Phe Thr Ala Tyr Ser Met His Trp Val Lys Gln
20 25 30
Thr Pro Gly Lys Gly Leu Lys Trp Leu Gly Trp Ile Asn Thr Glu Thr
35 40 45
Gly Glu Pro Thr Tyr Thr Asp Asp Phe Lys Gly Arg Phe Thr Phe Ser
50 55 60
Leu Glu Thr Ser Ala Arg Ile Ala Tyr Leu Gln Ile Asn Asp Leu Lys
65 70 75 80
Asn Glu Asp Thr Ala Thr Tyr Phe Cys Ala Arg Arg Ile Tyr Tyr Phe
85 90 95
Gly Arg Gly Gly Phe Asp Tyr Trp Gly Gln Gly Thr Thr Val Thr Val
100 105 110
Ser Ser
<210> 107
<211> 118
<212> PRT
<213> 小鼠(Mus musculus)
<400> 107
Pro Ala Ser Ser Ser Asp Val Leu Met Thr Gln Thr Pro Leu Ser Leu
1 5 10 15
Pro Val Arg Leu Gly Asp Gln Ser Ser Ile Ser Cys Arg Ser Ser Gln
20 25 30
Ser Ile Val His Ser Asn Gly Asn Thr Tyr Leu Glu Trp Tyr Leu Gln
35 40 45
Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile Tyr Lys Val Ser Asn Arg
50 55 60
Phe Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp
65 70 75 80
Phe Thr Leu Lys Ile Ser Arg Val Glu Pro Glu Asp Leu Gly Val Tyr
85 90 95
Tyr Cys Phe Gln Gly Ser His Val Pro Tyr Thr Ser Glu Gly Asp Gln
100 105 110
Ala Glu Ile Lys Leu Ala
115
<210> 108
<211> 114
<212> PRT
<213> 小鼠(Mus musculus)
<400> 108
Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Met Arg Leu Ser Cys Val
1 5 10 15
Ala Ser Gly Phe Thr Phe Ser Asn Ser Trp Phe Asn Trp Val Arg Gln
20 25 30
Ser Pro Glu Lys Gly Leu Glu Trp Val Ala Glu Ile Arg Leu Thr Ser
35 40 45
Asp Asn Tyr Ala Ile Tyr Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr
50 55 60
Ile Ser Arg Asp Asp Ser Lys Ser Ser Val Tyr Leu Gln Met Asn Asn
65 70 75 80
Leu Arg Ala Glu Asp Thr Gly Ile Tyr Tyr Cys Thr Arg Pro Glu Thr
85 90 95
Ala Arg Ala Thr Phe Ala Tyr Trp Gly Gln Gly Thr Thr Val Thr Val
100 105 110
Ser Ser
<210> 109
<211> 118
<212> PRT
<213> 小鼠(Mus musculus)
<400> 109
Pro Ala Ser Thr Ser Asp Val Leu Met Thr Gln Thr Pro Leu Ser Leu
1 5 10 15
Pro Val Ser Leu Gly Asp Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln
20 25 30
Ser Ile Val His Ser Asn Gly Asn Thr Tyr Leu Glu Trp Tyr Leu Gln
35 40 45
Lys Pro Gly Gln Ser Pro Lys Val Leu Ile Tyr Lys Val Phe Asn Arg
50 55 60
Phe Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp
65 70 75 80
Phe Thr Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr
85 90 95
Tyr Cys Phe Gln Gly Ser His Val Pro Arg Thr Phe Gly Gly Gly Thr
100 105 110
Lys Leu Asn Gln Thr Gly
115
<210> 110
<211> 111
<212> PRT
<213> 小鼠(Mus musculus)
<400> 110
Gly Pro Asp Leu Val Lys Pro Gly Ala Ser Val Lys Ile Ser Cys Lys
1 5 10 15
Ala Ser Gly Tyr Ser Phe Thr Ala Tyr Tyr Met His Trp Val Lys Gln
20 25 30
Ser His Gly Lys Ser Leu Glu Trp Ile Gly Arg Val Asn Pro Asn Asn
35 40 45
Gly Gly Thr Thr Tyr Asn Gln Lys Phe Lys Gly Lys Ala Ile Leu Thr
50 55 60
Val Asp Lys Ser Ser Ser Thr Ala Tyr Met Glu Leu Arg Ser Leu Thr
65 70 75 80
Phe Glu Asp Ser Ala Val Tyr Tyr Cys Ala Arg Arg Ile Tyr Tyr Gly
85 90 95
Tyr Phe Asp Tyr Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser
100 105 110
<210> 111
<211> 104
<212> PRT
<213> 小鼠(Mus musculus)
<400> 111
Ala Phe Phe Ala Val Ser Leu Gly Gln Arg Ala Thr Ile Ser Cys Lys
1 5 10 15
Ala Ser Gln Ser Val Asp Tyr Asp Gly Asp Ser Tyr Met Asn Trp Tyr
20 25 30
Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Val Ala Ser
35 40 45
Asn Leu Glu Ser Gly Val Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly
50 55 60
Thr Asp Phe Thr Leu Asn Ile His Pro Val Glu Glu Glu Asp Ala Ala
65 70 75 80
Thr Tyr Tyr Cys Gln Gln Ser Asn Glu Asp Pro Tyr Thr Phe Gly Gly
85 90 95
Gly Thr Lys Leu Glu Ile Lys Gln
100
<210> 112
<211> 106
<212> PRT
<213> 小鼠(Mus musculus)
<400> 112
Gly Ala Glu Leu Val Lys Pro Gly Ala Ser Val Lys Leu Ser Cys Thr
1 5 10 15
Ala Ser Gly Leu Asn Ile Arg Asp Ile Tyr Met His Trp Val Lys Gln
20 25 30
Arg Pro Glu Gln Gly Leu Glu Trp Ile Gly Lys Ile Asp Pro Ala Asn
35 40 45
Gly Asn Thr Lys Tyr Asp Pro Lys Phe Gln Gly Lys Ala Thr Ile Thr
50 55 60
Ala Asp Thr Ser Ser Asn Thr Ala Tyr Val Gln Leu Ser Ser Leu Thr
65 70 75 80
Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly Thr Gly Asp Tyr Trp
85 90 95
Gly Gln Gly Thr Thr Val Thr Val Ser Ser
100 105
<210> 113
<211> 112
<212> PRT
<213> 小鼠(Mus musculus)
<400> 113
Gly Thr Cys Gly Asp Ile Val Met Ser Gln Ser Pro Ser Ser Leu Ala
1 5 10 15
Val Ser Ala Gly Glu Lys Val Thr Met Ser Cys Lys Ser Ser Gln Ser
20 25 30
Leu Leu Asn Ser Arg Thr Arg Lys Asn Tyr Leu Ala Trp Val Gln His
35 40 45
Lys Pro Gly Gln Ser Pro Arg Leu Leu Ile Tyr Trp Ala Ser Thr Arg
50 55 60
Glu Ser Gly Val Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp
65 70 75 80
Phe Thr Leu Thr Ile Ser Ser Val Gln Ala Glu Asp Leu Ala Val Tyr
85 90 95
Tyr Cys Arg Gln Ser Tyr Asn Leu Val Thr Phe Gly Ala Gly Pro Ser
100 105 110
<210> 114
<211> 112
<212> PRT
<213> 小鼠(Mus musculus)
<400> 114
Gly Pro Glu Leu Val Lys Pro Gly Ala Ser Val Lys Met Ser Cys Lys
1 5 10 15
Ala Ser Gly Tyr Thr Phe Thr Ser Tyr Val Met His Trp Val Lys Gln
20 25 30
Lys Pro Gly Gln Gly Leu Glu Trp Ile Gly Tyr Ile Asn Pro Tyr Asn
35 40 45
Asp Gly Thr Lys Tyr Asn Glu Lys Phe Lys Gly Lys Ala Thr Leu Thr
50 55 60
Ser Asp Lys Ser Ser Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Thr
65 70 75 80
Ser Glu Asp Ser Ala Val Tyr Tyr Cys Ala Arg Arg Tyr Tyr Tyr Gly
85 90 95
Ser Ser Gly Gly Tyr Phe Asp Val Trp Ala Gln Asp His Val Arg Thr
100 105 110
<210> 115
<211> 108
<212> PRT
<213> 小鼠(Mus musculus)
<400> 115
Asp Val Gln Ile Thr Gln Ser Pro Ser Tyr Leu Ala Ala Ser Pro Gly
1 5 10 15
Glu Thr Ile Thr Ile Asn Cys Arg Ala Ser Lys Ser Ile Ser Lys Tyr
20 25 30
Leu Ala Trp Tyr Gln Glu Lys Pro Gly Lys Thr Asn Lys Leu Leu Ile
35 40 45
Tyr Ser Gly Ser Thr Leu Gln Ser Gly Ile Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro
65 70 75 80
Glu Asp Phe Ala Met Tyr Tyr Cys Gln Gln His Asn Glu Tyr Pro Tyr
85 90 95
Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg
100 105
<210> 116
<211> 113
<212> PRT
<213> 小鼠(Mus musculus)
<400> 116
Gly Pro Glu Leu Val Lys Pro Gly Ala Ser Val Lys Ile Ser Cys Lys
1 5 10 15
Ala Ser Gly Tyr Ser Phe Thr Gly Tyr Phe Met Asn Trp Val Met Gln
20 25 30
Ser His Gly Lys Ser Leu Glu Trp Ile Gly Arg Ile Asn Pro Tyr Asn
35 40 45
Gly Asp Thr Phe Tyr Asn Gln Lys Phe Lys Gly Lys Ala Thr Leu Thr
50 55 60
Val Asp Lys Ser Ser Ser Thr Ala His Met Glu Leu Arg Ser Leu Ala
65 70 75 80
Ser Glu Asp Ser Ala Val Tyr Tyr Cys Ala Arg Arg Ile His Tyr Tyr
85 90 95
Tyr Gly Ser Ser Tyr Tyr Ala Met Asp Tyr Trp Gly Gln Glu Pro His
100 105 110
His
<210> 117
<211> 108
<212> PRT
<213> 小鼠(Mus musculus)
<400> 117
Asp Val Gln Ile Thr Gln Ser Pro Ser Tyr Leu Ala Ala Ser Pro Gly
1 5 10 15
Glu Thr Ile Thr Ile Asn Cys Arg Ala Ser Lys Ser Ile Ser Lys Tyr
20 25 30
Leu Ala Trp Tyr Gln Glu Lys Pro Gly Lys Thr Asn Lys Leu Leu Ile
35 40 45
Tyr Ser Gly Ser Thr Leu Gln Ser Gly Ile Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro
65 70 75 80
Glu Asp Phe Ala Met Tyr Tyr Cys Gln Gln His Asn Glu Tyr Pro Trp
85 90 95
Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg
100 105
<210> 118
<211> 113
<212> PRT
<213> 小鼠(Mus musculus)
<400> 118
Gly Ala Gly Leu Val Lys Pro Gly Ala Ser Val Lys Leu Ser Cys Lys
1 5 10 15
Ala Ser Gly Tyr Thr Phe Thr Glu Tyr Ile Ile His Trp Val Lys Gln
20 25 30
Arg Ser Gly Gln Gly Leu Glu Trp Ile Gly Trp Phe Tyr Pro Gly Ser
35 40 45
Gly Ser Ile Lys Tyr Asn Glu Lys Phe Lys Asp Lys Ala Thr Leu Thr
50 55 60
Ala Asp Lys Ser Ser Ser Thr Val Tyr Met Glu Leu Ser Arg Leu Thr
65 70 75 80
Ser Glu Asp Ser Ala Val Tyr Phe Cys Ala Arg His Glu Val Tyr Tyr
85 90 95
Asp Tyr Asp Lys Ser Met Leu Trp Thr Thr Gly Val Lys Asn Leu Ile
100 105 110
Arg
<210> 119
<211> 108
<212> PRT
<213> 小鼠(Mus musculus)
<400> 119
Ser Pro Ser Ser Leu Ala Val Ser Val Gly Glu Lys Val Thr Met Ser
1 5 10 15
Cys Lys Ser Ser Gln Ser Leu Leu Tyr Ser Ser Asn Gln Lys Asn Tyr
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile
35 40 45
Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Thr Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Val Lys Ala
65 70 75 80
Glu Asp Leu Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Tyr Pro Tyr
85 90 95
Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg
100 105
<210> 120
<211> 113
<212> PRT
<213> 小鼠(Mus musculus)
<400> 120
Gly Ala Glu Leu Val Arg Pro Gly Thr Ser Val Lys Val Ser Cys Lys
1 5 10 15
Ala Ser Val Tyr Ala Phe Thr Asn Tyr Leu Ile Glu Trp Val Lys Gln
20 25 30
Arg Pro Gly Gln Gly Leu Glu Trp Ile Gly Val Ile Asn Pro Lys Ser
35 40 45
Gly Gly Thr Lys Tyr Asn Glu Lys Phe Arg Gly Lys Ala Thr Leu Thr
50 55 60
Ala Asp Lys Ser Ser Ser Thr Ala Tyr Met Gln Leu Ser Ser Leu Thr
65 70 75 80
Ser Gly Asp Ser Ala Val Tyr Phe Cys Ala Ile Thr Gly Thr Asp Tyr
85 90 95
Trp Gly Gln Gly Thr Thr Leu Thr Val Ser Ser Ala Lys Thr Thr Pro
100 105 110
Pro
<210> 121
<211> 113
<212> PRT
<213> 小鼠(Mus musculus)
<400> 121
Gln Gly Thr Arg Cys Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu
1 5 10 15
Ser Ala Ser Leu Gly Asp Arg Val Thr Ile Ser Cys Ser Ala Ser Gln
20 25 30
Gly Ile Asn Asn Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr
35 40 45
Val Lys Leu Leu Ile Tyr Tyr Thr Ser Ser Leu Arg Ser Gly Val Pro
50 55 60
Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile
65 70 75 80
Ser Asn Leu Glu Pro Glu Asp Val Ala Thr Tyr Tyr Cys Gln Gln Tyr
85 90 95
Ser Lys Leu Pro Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg
<210> 122
<211> 121
<212> PRT
<213> 人(Homo sapiens)
<400> 122
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Leu Ser Ser His
20 25 30
Ser Leu Gly Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Asp Ile Arg Ser Gly Gly Ser Ala Tyr Tyr Ala Asn Trp Ala Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Thr
85 90 95
Arg Thr Asn Gly Pro Ser Asp Leu Thr Asn Arg Leu Asp Leu Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 123
<211> 112
<212> PRT
<213> 人(Homo sapiens)
<400> 123
Gln Val Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp
1 5 10 15
Arg Val Thr Ile Asn Cys Gln Ala Ser Gln Ser Leu Tyr Asn Asn Glu
20 25 30
Asn Leu Ala Trp Phe Gln Gln Lys Pro Gly Lys Val Pro Lys Arg Leu
35 40 45
Ile Tyr Gly Ala Ser Thr Leu Ala Ser Gly Val Ser Ser Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln
65 70 75 80
Cys Glu Asp Phe Ala Ile Tyr Tyr Cys Leu Gly Glu Phe Ser Cys Gly
85 90 95
Ser Ala Asp Cys Phe Ala Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105 110
<210> 124
<211> 121
<212> PRT
<213> 人(Homo sapiens)
<400> 124
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Leu Ser Ser His
20 25 30
Ser Leu Gly Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Asp Ile Arg Ser Gly Gly Ser Ala Tyr Tyr Ala Asn Trp Ala Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Phe Cys Thr
85 90 95
Arg Thr Asn Gly Pro Ser Asp Leu Thr Asn Arg Leu Asp Leu Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 125
<211> 112
<212> PRT
<213> 人(Homo sapiens)
<400> 125
Gln Val Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp
1 5 10 15
Arg Val Thr Ile Asn Cys Gln Ala Ser Gln Ser Leu Tyr Asn Asn Glu
20 25 30
Asn Leu Ala Trp Phe Gln Gln Lys Pro Gly Lys Val Pro Lys Arg Leu
35 40 45
Ile Tyr Gly Ala Ser Thr Leu Ala Ser Gly Val Ser Ser Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln
65 70 75 80
Cys Glu Asp Phe Ala Ile Tyr Tyr Cys Leu Gly Glu Phe Ser Cys Gly
85 90 95
Ser Ala Asp Cys Phe Ala Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105 110
<210> 126
<211> 121
<212> PRT
<213> 人(Homo sapiens)
<400> 126
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Leu Ser Ser His
20 25 30
Ser Leu Gly Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Asp Ile Arg Ser Gly Gly Ser Ala Tyr Tyr Ala Asn Trp Ala Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Thr
85 90 95
Arg Thr Asn Gly Pro Ser Asp Leu Thr Asn Arg Leu Asp Leu Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 127
<211> 113
<212> PRT
<213> 人(Homo sapiens)
<400> 127
Glu Gln Val Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Asn Cys Gln Ala Ser Gln Ser Leu Tyr Asn Asn
20 25 30
Glu Asn Leu Ala Trp Phe Gln Gln Lys Pro Gly Lys Val Pro Lys Arg
35 40 45
Leu Ile Tyr Gly Ala Ser Thr Leu Ala Ser Gly Val Ser Ser Arg Phe
50 55 60
Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Asn Leu
65 70 75 80
Gln Pro Glu Asp Phe Ala Ile Tyr Tyr Cys Leu Gly Glu Phe Ser Cys
85 90 95
Gly Ser Ala Asp Cys Phe Ala Phe Gly Gly Gly Thr Lys Val Glu Ile
100 105 110
Lys
<210> 128
<211> 121
<212> PRT
<213> 人(Homo sapiens)
<400> 128
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Leu Ser Ser His
20 25 30
Ser Leu Gly Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Asp Ile Arg Ser Gly Gly Ser Ala Tyr Tyr Ala Asn Trp Ala Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Phe Cys Thr
85 90 95
Arg Thr Asn Gly Pro Ser Asp Leu Thr Asn Arg Leu Asp Leu Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 129
<211> 113
<212> PRT
<213> 人(Homo sapiens)
<400> 129
Glu Ile Val Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Asn Cys Gln Ala Ser Gln Ser Leu Tyr Asn Asn
20 25 30
Glu Asn Leu Ala Trp Phe Gln Gln Lys Pro Gly Lys Val Pro Lys Arg
35 40 45
Leu Ile Tyr Gly Ala Ser Thr Leu Ala Ser Gly Val Ser Ser Arg Phe
50 55 60
Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Asn Leu
65 70 75 80
Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Leu Gly Glu Phe Ser Cys
85 90 95
Gly Ser Ala Asp Cys Phe Ala Phe Gly Gly Gly Thr Lys Val Glu Ile
100 105 110
Lys
<210> 130
<211> 121
<212> PRT
<213> 人(Homo sapiens)
<400> 130
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Leu Ser Ser His
20 25 30
Ser Leu Gly Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Asp Ile Arg Ser Gly Gly Ser Ala Tyr Tyr Ala Asn Trp Ala Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Thr
85 90 95
Arg Thr Asn Gly Pro Ser Asp Leu Thr Asn Arg Leu Asp Leu Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 131
<211> 113
<212> PRT
<213> 人(Homo sapiens)
<400> 131
Glu Ile Val Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Asn Cys Gln Ala Ser Gln Ser Leu Tyr Asn Asn
20 25 30
Glu Asn Leu Ala Trp Phe Gln Gln Lys Pro Gly Lys Val Pro Lys Arg
35 40 45
Leu Ile Tyr Gly Ala Ser Thr Leu Ala Ser Gly Val Ser Ser Arg Phe
50 55 60
Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Asn Leu
65 70 75 80
Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Leu Gly Glu Phe Ser Cys
85 90 95
Gly Ser Ala Asp Cys Phe Ala Phe Gly Gly Gly Thr Lys Val Glu Ile
100 105 110
Lys
<210> 132
<211> 121
<212> PRT
<213> 人(Homo sapiens)
<400> 132
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Leu Ser Ser His
20 25 30
Ser Leu Gly Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Asp Ile Arg Ser Gly Gly Ser Ala Tyr Tyr Ala Asn Trp Ala Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Phe Cys Thr
85 90 95
Arg Thr Asn Gly Pro Ser Asp Leu Thr Asn Arg Leu Asp Leu Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 133
<211> 113
<212> PRT
<213> 人(Homo sapiens)
<400> 133
Glu Gln Val Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Asn Cys Gln Ala Ser Gln Ser Leu Tyr Asn Asn
20 25 30
Glu Asn Leu Ala Trp Phe Gln Gln Lys Pro Gly Lys Val Pro Lys Arg
35 40 45
Leu Ile Tyr Gly Ala Ser Thr Leu Ala Ser Gly Val Ser Ser Arg Phe
50 55 60
Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Asn Leu
65 70 75 80
Gln Pro Glu Asp Phe Ala Ile Tyr Tyr Cys Leu Gly Glu Phe Ser Cys
85 90 95
Gly Ser Ala Asp Cys Phe Ala Phe Gly Gly Gly Thr Lys Val Glu Ile
100 105 110
Lys
<210> 134
<211> 5
<212> PRT
<213> 鸡(Gallus gallus)
<400> 134
Gly Tyr Asp Met Leu
1 5
<210> 135
<211> 17
<212> PRT
<213> 鸡(Gallus gallus)
<400> 135
Gly Ile Gly Ser Thr Gly Gly Gly Thr Asp Tyr Gly Ala Ala Val Lys
1 5 10 15
Gly
<210> 136
<211> 19
<212> PRT
<213> 鸡(Gallus gallus)
<400> 136
Val Ala Gly Gly Cys Asn Ser Gly Tyr Cys Arg Asp Ser Pro Gly Ser
1 5 10 15
Ile Asp Ala
<210> 137
<211> 10
<212> PRT
<213> 鸡(Gallus gallus)
<400> 137
Ser Gly Gly Gly Ser Arg Asn Tyr Tyr Gly
1 5 10
<210> 138
<211> 7
<212> PRT
<213> 鸡(Gallus gallus)
<400> 138
Asp Asp Gln Arg Pro Ser Asn
1 5
<210> 139
<211> 11
<212> PRT
<213> 鸡(Gallus gallus)
<400> 139
Ser Ala Asp Ser Asn Thr Tyr Glu Gly Ser Phe
1 5 10
<210> 140
<211> 5
<212> PRT
<213> 小鼠(Mus musculus)
<400> 140
Asp Tyr Asn Met Asp
1 5
<210> 141
<211> 17
<212> PRT
<213> 小鼠(Mus musculus)
<400> 141
Asp Ile Asn Pro Asn Tyr Asp Ser Thr Ser Tyr Asn Gln Lys Phe Lys
1 5 10 15
Gly
<210> 142
<211> 11
<212> PRT
<213> 小鼠(Mus musculus)
<400> 142
Ser Arg Ser Tyr Asp Tyr Glu Gly Phe Ala Tyr
1 5 10
<210> 143
<211> 11
<212> PRT
<213> 小鼠(Mus musculus)
<400> 143
Leu Ser Ile Val Asn Arg Tyr His Tyr Met Ser
1 5 10
<210> 144
<211> 6
<212> PRT
<213> 小鼠(Mus musculus)
<400> 144
Glu Ala Ser Ile Thr Lys
1 5
<210> 145
<211> 9
<212> PRT
<213> 小鼠(Mus musculus)
<400> 145
Gln His Asn Arg Gly Ser Phe Leu Pro
1 5
<210> 146
<211> 5
<212> PRT
<213> 小鼠(Mus musculus)
<400> 146
Asp Tyr Tyr Met Ser
1 5
<210> 147
<211> 17
<212> PRT
<213> 小鼠(Mus musculus)
<400> 147
Arg Asn Lys Ala Asn Gly Tyr Thr Thr Glu Tyr Ser Ala Ser Val Lys
1 5 10 15
Gly
<210> 148
<211> 9
<212> PRT
<213> 小鼠(Mus musculus)
<400> 148
Ala Arg Ala Asn Trp Ala Phe Asp Tyr
1 5
<210> 149
<211> 11
<212> PRT
<213> 小鼠(Mus musculus)
<400> 149
Arg Ala Ser Gln Ser Ile Ser Asn Tyr Leu His
1 5 10
<210> 150
<211> 7
<212> PRT
<213> 小鼠(Mus musculus)
<400> 150
Tyr Ala Ser Gln Ser Ile Ser
1 5
<210> 151
<211> 7
<212> PRT
<213> 小鼠(Mus musculus)
<400> 151
Tyr Ala Ser Gln Ser Ile Ser
1 5
<210> 152
<211> 5
<212> PRT
<213> 小鼠(Mus musculus)
<400> 152
Asn Tyr Leu Ile Val
1 5
<210> 153
<211> 17
<212> PRT
<213> 小鼠(Mus musculus)
<400> 153
Val Ile Ser Pro Gly Ser Gly Gly Thr Asn Tyr Asn Glu Lys Phe Lys
1 5 10 15
Gly
<210> 154
<211> 11
<212> PRT
<213> 小鼠(Mus musculus)
<400> 154
Glu Lys Ile Tyr Asp Asp Tyr Tyr Glu Gly Tyr
1 5 10
<210> 155
<211> 15
<212> PRT
<213> 小鼠(Mus musculus)
<400> 155
Thr Ile Ser Cys Ser Ala Ser Leu Gly Ile Gly Asn Tyr Leu Asn
1 5 10 15
<210> 156
<211> 7
<212> PRT
<213> 小鼠(Mus musculus)
<400> 156
Thr Ser Asn Leu His Ser Gly
1 5
<210> 157
<211> 9
<212> PRT
<213> 小鼠(Mus musculus)
<400> 157
His Tyr Ser Lys Leu Pro Leu Thr Phe
1 5
<210> 158
<211> 5
<212> PRT
<213> 小鼠(Mus musculus)
<400> 158
Asp Tyr Asn Met Tyr
1 5
<210> 159
<211> 17
<212> PRT
<213> 小鼠(Mus musculus)
<400> 159
Tyr Ile Tyr Pro Gly Asn Gly Gly Thr Asn Tyr Asn Gln Lys Phe Lys
1 5 10 15
Gly
<210> 160
<211> 11
<212> PRT
<213> 小鼠(Mus musculus)
<400> 160
Asp Tyr Asp Asp Gly Gly Tyr Ala Met Asp Tyr
1 5 10
<210> 161
<211> 15
<212> PRT
<213> 小鼠(Mus musculus)
<400> 161
Ser Val Gly Glu Thr Val Thr Ile Thr Cys Arg Ala Ser Gly Asn
1 5 10 15
<210> 162
<211> 7
<212> PRT
<213> 小鼠(Mus musculus)
<400> 162
Asn Ala Lys Thr Leu Ala Asp
1 5
<210> 163
<211> 9
<212> PRT
<213> 小鼠(Mus musculus)
<400> 163
Gln His Phe Trp Asn Ile Pro Trp Thr
1 5
<210> 164
<211> 5
<212> PRT
<213> 小鼠(Mus musculus)
<400> 164
Asp His Ser Ile His
1 5
<210> 165
<211> 17
<212> PRT
<213> 小鼠(Mus musculus)
<400> 165
Tyr Ile Ser Pro Gly Asn Gly Asn Ile Lys Tyr Asn Glu Lys Phe Lys
1 5 10 15
Gly
<210> 166
<211> 12
<212> PRT
<213> 小鼠(Mus musculus)
<400> 166
Ser Leu Gly Arg Gly Gly Pro Tyr Tyr Phe Asp Tyr
1 5 10
<210> 167
<211> 16
<212> PRT
<213> 小鼠(Mus musculus)
<400> 167
Arg Ser Ser Lys Ser Leu Leu His Ser Asn Gly Asn Thr Tyr Leu Tyr
1 5 10 15
<210> 168
<211> 7
<212> PRT
<213> 小鼠(Mus musculus)
<400> 168
Arg Met Ser Asn Leu Ala Ser
1 5
<210> 169
<211> 9
<212> PRT
<213> 小鼠(Mus musculus)
<400> 169
Met Gln His Arg Glu Tyr Pro Val Thr
1 5
<210> 170
<211> 5
<212> PRT
<213> 小鼠(Mus musculus)
<400> 170
Ser Tyr Trp Ile Glu
1 5
<210> 171
<211> 17
<212> PRT
<213> 小鼠(Mus musculus)
<400> 171
Glu Ile Leu Pro Gly Ser Gly Ser Thr Asn Tyr Asn Glu Lys Phe Lys
1 5 10 15
Gly
<210> 172
<211> 11
<212> PRT
<213> 小鼠(Mus musculus)
<400> 172
Tyr Tyr Trp Tyr Phe Asp Val Trp Ala Gln Asp
1 5 10
<210> 173
<211> 15
<212> PRT
<213> 小鼠(Mus musculus)
<400> 173
Ser Ser Lys Asn Leu Leu His Ser Asn Gly Ile Thr Tyr Leu Tyr
1 5 10 15
<210> 174
<211> 7
<212> PRT
<213> 小鼠(Mus musculus)
<400> 174
Arg Val Ser Asn Leu Ala Ser
1 5
<210> 175
<211> 9
<212> PRT
<213> 小鼠(Mus musculus)
<400> 175
Ala Gln Leu Leu Glu Leu Pro Tyr Thr
1 5
<210> 176
<211> 5
<212> PRT
<213> 小鼠(Mus musculus)
<400> 176
Ser Tyr Asp Met Ser
1 5
<210> 177
<211> 17
<212> PRT
<213> 小鼠(Mus musculus)
<400> 177
Tyr Ile Ser Ser Gly Ala Gly Ser Thr Tyr Tyr Pro Asp Thr Val Lys
1 5 10 15
Gly
<210> 178
<211> 11
<212> PRT
<213> 小鼠(Mus musculus)
<400> 178
His Phe Tyr Arg Phe Asp Tyr Trp Gly Gln Gly
1 5 10
<210> 179
<211> 15
<212> PRT
<213> 小鼠(Mus musculus)
<400> 179
Ser Ala Gly Asp Arg Ile Thr Ile Thr Cys Lys Ala Ser Gln Ser
1 5 10 15
<210> 180
<211> 7
<212> PRT
<213> 小鼠(Mus musculus)
<400> 180
Tyr Ala Ser Asn Arg Tyr Thr
1 5
<210> 181
<211> 9
<212> PRT
<213> 小鼠(Mus musculus)
<400> 181
Gln Gln Asp Asp Arg Phe Pro Leu Thr
1 5
<210> 182
<211> 5
<212> PRT
<213> 小鼠(Mus musculus)
<400> 182
Asn Tyr Gly Met Asn
1 5
<210> 183
<211> 17
<212> PRT
<213> 小鼠(Mus musculus)
<400> 183
Trp Ile Asn Thr Tyr Thr Gly Glu Pro Thr Tyr Ala Asp Asp Phe Lys
1 5 10 15
Gly
<210> 184
<211> 11
<212> PRT
<213> 小鼠(Mus musculus)
<400> 184
Gly Ala Trp Phe Ala Tyr Trp Ala Lys Asp Ser
1 5 10
<210> 185
<211> 15
<212> PRT
<213> 小鼠(Mus musculus)
<400> 185
Ser Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Thr Ala Val Ala
1 5 10 15
<210> 186
<211> 7
<212> PRT
<213> 小鼠(Mus musculus)
<400> 186
Trp Ala Ser Thr Arg His Thr
1 5
<210> 187
<211> 9
<212> PRT
<213> 小鼠(Mus musculus)
<400> 187
Gln Gln Tyr Ser Ser Tyr Pro Leu Thr
1 5
<210> 188
<211> 5
<212> PRT
<213> 小鼠(Mus musculus)
<400> 188
Asp Phe Trp Met Asn
1 5
<210> 189
<211> 19
<212> PRT
<213> 小鼠(Mus musculus)
<400> 189
Glu Ile Arg Leu Lys Ser Asn Asn Tyr Ala Thr His Tyr Ala Glu Ser
1 5 10 15
Val Lys Gly
<210> 190
<211> 13
<212> PRT
<213> 小鼠(Mus musculus)
<400> 190
Leu Phe Tyr Tyr Tyr Asp Gly Thr Ser Gly Phe Ala Tyr
1 5 10
<210> 191
<211> 17
<212> PRT
<213> 小鼠(Mus musculus)
<400> 191
Lys Ser Ser Gln Ser Leu Leu Asn Ser Gly Asp Gln Lys Asn Tyr Leu
1 5 10 15
Thr
<210> 192
<211> 7
<212> PRT
<213> 小鼠(Mus musculus)
<400> 192
Trp Ala Ser Thr Arg Glu Ser
1 5
<210> 193
<211> 9
<212> PRT
<213> 小鼠(Mus musculus)
<400> 193
Gln Asn Asp Tyr Asp Tyr Pro Leu Thr
1 5
<210> 194
<211> 5
<212> PRT
<213> 小鼠(Mus musculus)
<400> 194
Asp Tyr Asn Met Asp
1 5
<210> 195
<211> 17
<212> PRT
<213> 小鼠(Mus musculus)
<400> 195
Asp Ile Asn Pro Asn Tyr Asp Ser Thr Ser Tyr Asn Gln Lys Phe Lys
1 5 10 15
Gly
<210> 196
<211> 11
<212> PRT
<213> 小鼠(Mus musculus)
<400> 196
Ser Arg Ser Tyr Asp Tyr Glu Gly Phe Ala Tyr
1 5 10
<210> 197
<211> 11
<212> PRT
<213> 小鼠(Mus musculus)
<400> 197
Arg Ala Ser Gly Asn Ile His Asn Tyr Leu Ala
1 5 10
<210> 198
<211> 7
<212> PRT
<213> 小鼠(Mus musculus)
<400> 198
Asn Ala Lys Thr Leu Ala Asp
1 5
<210> 199
<211> 8
<212> PRT
<213> 小鼠(Mus musculus)
<400> 199
Gln His Phe Trp Ser Thr Leu Thr
1 5
<210> 200
<211> 5
<212> PRT
<213> 小鼠(Mus musculus)
<400> 200
Gly Tyr Thr Met Asn
1 5
<210> 201
<211> 16
<212> PRT
<213> 小鼠(Mus musculus)
<400> 201
Asn Pro Tyr Asn Gly Gly Thr Ser Tyr Asn Gln Lys Phe Lys Gly Lys
1 5 10 15
<210> 202
<211> 9
<212> PRT
<213> 小鼠(Mus musculus)
<400> 202
Trp Gly Val Trp Ser Ala Met Asp Tyr
1 5
<210> 203
<211> 11
<212> PRT
<213> 小鼠(Mus musculus)
<400> 203
Lys Ala Ser Gln Asn Val Arg Thr Ala Val Ala
1 5 10
<210> 204
<211> 7
<212> PRT
<213> 小鼠(Mus musculus)
<400> 204
Leu Ala Ser Asn Arg Asp Thr
1 5
<210> 205
<211> 9
<212> PRT
<213> 小鼠(Mus musculus)
<400> 205
Leu Gln His Cys Asn Tyr Pro Asn Glu
1 5
<210> 206
<211> 5
<212> PRT
<213> 小鼠(Mus musculus)
<400> 206
Ser Tyr Trp Met Gln
1 5
<210> 207
<211> 17
<212> PRT
<213> 小鼠(Mus musculus)
<400> 207
Ala Ile Tyr Pro Gly Asp Gly Asp Thr Arg Tyr Thr Gln Lys Phe Lys
1 5 10 15
Gly
<210> 208
<211> 11
<212> PRT
<213> 小鼠(Mus musculus)
<400> 208
Ala Arg Gly Glu Tyr Gly Asn Tyr Phe Ala Tyr
1 5 10
<210> 209
<211> 11
<212> PRT
<213> 小鼠(Mus musculus)
<400> 209
Lys Ala Ser Gln Asp Ile Asn Ser Tyr Leu Ser
1 5 10
<210> 210
<211> 7
<212> PRT
<213> 小鼠(Mus musculus)
<400> 210
Arg Ala Asn Arg Leu Val Asp
1 5
<210> 211
<211> 9
<212> PRT
<213> 小鼠(Mus musculus)
<400> 211
Leu Gln Tyr Asp Glu Phe Pro Leu Thr
1 5
<210> 212
<211> 5
<212> PRT
<213> 小鼠(Mus musculus)
<400> 212
Asp Thr Tyr Met His
1 5
<210> 213
<211> 17
<212> PRT
<213> 小鼠(Mus musculus)
<400> 213
Arg Ile Asp Pro Ala Asn Gly Asn Thr Lys Tyr Asp Pro Lys Phe Gln
1 5 10 15
Gly
<210> 214
<211> 14
<212> PRT
<213> 小鼠(Mus musculus)
<400> 214
Ala Arg Pro Ile His Tyr Tyr Tyr Gly Ser Ser Leu Ala Tyr
1 5 10
<210> 215
<211> 11
<212> PRT
<213> 小鼠(Mus musculus)
<400> 215
Ser Val Asp Ser Tyr Gly Asn Ser Phe Met His
1 5 10
<210> 216
<211> 7
<212> PRT
<213> 小鼠(Mus musculus)
<400> 216
Arg Ala Ser Asn Leu Glu Ser
1 5
<210> 217
<211> 9
<212> PRT
<213> 小鼠(Mus musculus)
<400> 217
Gln Gln Ser Asn Glu Asp Pro Gly Arg
1 5
<210> 218
<211> 5
<212> PRT
<213> 小鼠(Mus musculus)
<400> 218
Asp Tyr Tyr Met Ser
1 5
<210> 219
<211> 17
<212> PRT
<213> 小鼠(Mus musculus)
<400> 219
Arg Asn Lys Ala Asn Gly Tyr Thr Thr Glu Tyr Ser Ala Ser Val Lys
1 5 10 15
Gly
<210> 220
<211> 9
<212> PRT
<213> 小鼠(Mus musculus)
<400> 220
Ala Arg Ala Asn Trp Ala Phe Asp Tyr
1 5
<210> 221
<211> 11
<212> PRT
<213> 小鼠(Mus musculus)
<400> 221
Arg Ala Ser Gln Ser Ile Ser Asn Tyr Leu His
1 5 10
<210> 222
<211> 7
<212> PRT
<213> 小鼠(Mus musculus)
<400> 222
Tyr Ala Ser Gln Ser Ile Ser
1 5
<210> 223
<211> 9
<212> PRT
<213> 小鼠(Mus musculus)
<400> 223
Gln Gln Ser Asn Ser Trp Pro Tyr Thr
1 5
<210> 224
<211> 5
<212> PRT
<213> 小鼠(Mus musculus)
<400> 224
Asp Tyr Tyr Met Ser
1 5
<210> 225
<211> 17
<212> PRT
<213> 小鼠(Mus musculus)
<400> 225
Arg Asn Lys Ala Asn Gly Tyr Thr Thr Glu Tyr Ser Ala Ser Val Lys
1 5 10 15
Gly
<210> 226
<211> 12
<212> PRT
<213> 小鼠(Mus musculus)
<400> 226
Ala Arg Ala Pro Leu Leu Tyr Tyr Ala Met Asp Tyr
1 5 10
<210> 227
<211> 11
<212> PRT
<213> 小鼠(Mus musculus)
<400> 227
Asn Val Ser Thr Ser Gly Tyr Ser Tyr Met His
1 5 10
<210> 228
<211> 7
<212> PRT
<213> 小鼠(Mus musculus)
<400> 228
Leu Val Ser Asn Leu Glu Ser
1 5
<210> 229
<211> 8
<212> PRT
<213> 小鼠(Mus musculus)
<400> 229
Gln His Ile Arg Glu Leu Thr Arg
1 5
<210> 230
<211> 5
<212> PRT
<213> 小鼠(Mus musculus)
<400> 230
Ser Tyr Trp Met His
1 5
<210> 231
<211> 17
<212> PRT
<213> 小鼠(Mus musculus)
<400> 231
Met Ile Asp Pro Ser Asn Ser Glu Thr Arg Leu Asn Gln Lys Phe Lys
1 5 10 15
Asp
<210> 232
<211> 12
<212> PRT
<213> 小鼠(Mus musculus)
<400> 232
Ala Arg Gly Leu Arg His Tyr Trp Tyr Phe Asp Val
1 5 10
<210> 233
<211> 11
<212> PRT
<213> 小鼠(Mus musculus)
<400> 233
Ser Val Ser Thr Ser Gly Tyr Ser Tyr Met His
1 5 10
<210> 234
<211> 7
<212> PRT
<213> 小鼠(Mus musculus)
<400> 234
Leu Val Ser Asn Leu Glu Ser
1 5
<210> 235
<211> 9
<212> PRT
<213> 小鼠(Mus musculus)
<400> 235
Gln His Ile Arg Glu Leu Thr Arg Ser
1 5
<210> 236
<211> 5
<212> PRT
<213> 小鼠(Mus musculus)
<400> 236
Ser Tyr Gly Met Ser
1 5
<210> 237
<211> 14
<212> PRT
<213> 小鼠(Mus musculus)
<400> 237
Trp Val Arg Gln Thr Pro Glu Lys Arg Leu Glu Trp Val Ala
1 5 10
<210> 238
<211> 11
<212> PRT
<213> 小鼠(Mus musculus)
<400> 238
Leu Ala Ser Tyr Tyr Phe Asp Tyr Trp Gly Gln
1 5 10
<210> 239
<211> 15
<212> PRT
<213> 小鼠(Mus musculus)
<400> 239
Thr Met Thr Cys Gln Ala Ser Gln Gly Thr Ser Ile Asn Leu Asn
1 5 10 15
<210> 240
<211> 7
<212> PRT
<213> 小鼠(Mus musculus)
<400> 240
Gly Ala Ser Ser Leu Glu Asp
1 5
<210> 241
<211> 11
<212> PRT
<213> 小鼠(Mus musculus)
<400> 241
Leu Gln His Ser Tyr Leu Pro Pro Leu Thr Phe
1 5 10
<210> 242
<211> 5
<212> PRT
<213> 小鼠(Mus musculus)
<400> 242
Thr Tyr Asp Leu His
1 5
<210> 243
<211> 16
<212> PRT
<213> 小鼠(Mus musculus)
<400> 243
Val Ile Trp Ser Gly Gly Ser Thr Asp Tyr Asn Ala Ala Phe Ile Ser
1 5 10 15
<210> 244
<211> 11
<212> PRT
<213> 小鼠(Mus musculus)
<400> 244
Asn Tyr Gly Tyr Ser Ala Trp Phe Ala Tyr Trp
1 5 10
<210> 245
<211> 15
<212> PRT
<213> 小鼠(Mus musculus)
<400> 245
Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Ile Val His Ser Asn
1 5 10 15
<210> 246
<211> 7
<212> PRT
<213> 小鼠(Mus musculus)
<400> 246
Lys Val Ser Asn Arg Phe Ser
1 5
<210> 247
<211> 9
<212> PRT
<213> 小鼠(Mus musculus)
<400> 247
Phe Gln Gly Ser His Val Pro Leu Thr
1 5
<210> 248
<211> 5
<212> PRT
<213> 小鼠(Mus musculus)
<400> 248
Ala Tyr Ser Met His
1 5
<210> 249
<211> 17
<212> PRT
<213> 小鼠(Mus musculus)
<400> 249
Trp Ile Asn Thr Glu Thr Gly Glu Pro Thr Tyr Thr Asp Asp Phe Lys
1 5 10 15
Gly
<210> 250
<211> 11
<212> PRT
<213> 小鼠(Mus musculus)
<400> 250
Arg Ile Tyr Tyr Phe Gly Arg Gly Gly Phe Asp
1 5 10
<210> 251
<211> 15
<212> PRT
<213> 小鼠(Mus musculus)
<400> 251
Ser Ser Ile Ser Cys Arg Ser Ser Gln Ser Ile Val His Ser Asn
1 5 10 15
<210> 252
<211> 7
<212> PRT
<213> 小鼠(Mus musculus)
<400> 252
Lys Val Ser Asn Arg Phe Ser
1 5
<210> 253
<211> 9
<212> PRT
<213> 小鼠(Mus musculus)
<400> 253
Phe Gln Gly Ser His Val Pro Tyr Thr
1 5
<210> 254
<211> 5
<212> PRT
<213> 小鼠(Mus musculus)
<400> 254
Asn Ser Trp Phe Asn
1 5
<210> 255
<211> 19
<212> PRT
<213> 小鼠(Mus musculus)
<400> 255
Glu Ile Arg Leu Thr Ser Asp Asn Tyr Ala Ile Tyr Tyr Ala Glu Ser
1 5 10 15
Val Lys Gly
<210> 256
<211> 11
<212> PRT
<213> 小鼠(Mus musculus)
<400> 256
Pro Glu Thr Ala Arg Ala Thr Phe Ala Tyr Trp
1 5 10
<210> 257
<211> 15
<212> PRT
<213> 小鼠(Mus musculus)
<400> 257
Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Ile Val His Ser Asn
1 5 10 15
<210> 258
<211> 7
<212> PRT
<213> 小鼠(Mus musculus)
<400> 258
Lys Val Phe Asn Arg Phe Ser
1 5
<210> 259
<211> 9
<212> PRT
<213> 小鼠(Mus musculus)
<400> 259
Phe Gln Gly Ser His Val Pro Arg Thr
1 5
<210> 260
<211> 5
<212> PRT
<213> 小鼠(Mus musculus)
<400> 260
Ala Tyr Tyr Met His
1 5
<210> 261
<211> 17
<212> PRT
<213> 小鼠(Mus musculus)
<400> 261
Arg Val Asn Pro Asn Asn Gly Gly Thr Thr Tyr Asn Gln Lys Phe Lys
1 5 10 15
Gly
<210> 262
<211> 11
<212> PRT
<213> 小鼠(Mus musculus)
<400> 262
Arg Ile Tyr Tyr Gly Tyr Phe Asp Tyr Trp Gly
1 5 10
<210> 263
<211> 15
<212> PRT
<213> 小鼠(Mus musculus)
<400> 263
Lys Ala Ser Gln Ser Val Asp Tyr Asp Gly Asp Ser Tyr Met Asn
1 5 10 15
<210> 264
<211> 7
<212> PRT
<213> 小鼠(Mus musculus)
<400> 264
Val Ala Ser Asn Leu Glu Ser
1 5
<210> 265
<211> 9
<212> PRT
<213> 小鼠(Mus musculus)
<400> 265
Gln Gln Ser Asn Glu Asp Pro Tyr Thr
1 5
<210> 266
<211> 4
<212> PRT
<213> 小鼠(Mus musculus)
<400> 266
Asp Ile Tyr Met
1
<210> 267
<211> 17
<212> PRT
<213> 小鼠(Mus musculus)
<400> 267
Lys Ile Asp Pro Ala Asn Gly Asn Thr Lys Tyr Asp Pro Lys Phe Gln
1 5 10 15
Gly
<210> 268
<211> 11
<212> PRT
<213> 小鼠(Mus musculus)
<400> 268
Thr Gly Asp Tyr Trp Gly Gln Gly Thr Thr Val
1 5 10
<210> 269
<211> 15
<212> PRT
<213> 小鼠(Mus musculus)
<400> 269
Thr Met Ser Cys Lys Ser Ser Gln Ser Leu Leu Asn Ser Arg Thr
1 5 10 15
<210> 270
<211> 7
<212> PRT
<213> 小鼠(Mus musculus)
<400> 270
Trp Ala Ser Thr Arg Glu Ser
1 5
<210> 271
<211> 9
<212> PRT
<213> 小鼠(Mus musculus)
<400> 271
Arg Gln Ser Tyr Asn Leu Val Thr Phe
1 5
<210> 272
<211> 5
<212> PRT
<213> 小鼠(Mus musculus)
<400> 272
Ser Tyr Val Met His
1 5
<210> 273
<211> 17
<212> PRT
<213> 小鼠(Mus musculus)
<400> 273
Tyr Ile Asn Pro Tyr Asn Asp Gly Thr Lys Tyr Asn Glu Lys Phe Lys
1 5 10 15
Gly
<210> 274
<211> 11
<212> PRT
<213> 小鼠(Mus musculus)
<400> 274
Arg Tyr Tyr Tyr Gly Ser Ser Gly Gly Tyr Phe
1 5 10
<210> 275
<211> 15
<212> PRT
<213> 小鼠(Mus musculus)
<400> 275
Arg Ala Ser Lys Ser Ile Ser Lys Tyr Leu Ala Trp Tyr Gln Glu
1 5 10 15
<210> 276
<211> 7
<212> PRT
<213> 小鼠(Mus musculus)
<400> 276
Ser Gly Ser Thr Leu Gln Ser
1 5
<210> 277
<211> 9
<212> PRT
<213> 小鼠(Mus musculus)
<400> 277
Gln Gln His Asn Glu Tyr Pro Tyr Thr
1 5
<210> 278
<211> 5
<212> PRT
<213> 小鼠(Mus musculus)
<400> 278
Gly Tyr Phe Met Asn
1 5
<210> 279
<211> 17
<212> PRT
<213> 小鼠(Mus musculus)
<400> 279
Arg Ile Asn Pro Tyr Asn Gly Asp Thr Phe Tyr Asn Gln Lys Phe Lys
1 5 10 15
Gly
<210> 280
<211> 11
<212> PRT
<213> 小鼠(Mus musculus)
<400> 280
Arg Ile His Tyr Tyr Tyr Gly Ser Ser Tyr Tyr
1 5 10
<210> 281
<211> 15
<212> PRT
<213> 小鼠(Mus musculus)
<400> 281
Arg Ala Ser Lys Ser Ile Ser Lys Tyr Leu Ala Trp Tyr Gln Glu
1 5 10 15
<210> 282
<211> 7
<212> PRT
<213> 小鼠(Mus musculus)
<400> 282
Ser Gly Ser Thr Leu Gln Ser
1 5
<210> 283
<211> 9
<212> PRT
<213> 小鼠(Mus musculus)
<400> 283
Gln Gln His Asn Glu Tyr Pro Trp Thr
1 5
<210> 284
<211> 5
<212> PRT
<213> 小鼠(Mus musculus)
<400> 284
Glu Tyr Ile Ile His
1 5
<210> 285
<211> 17
<212> PRT
<213> 小鼠(Mus musculus)
<400> 285
Trp Phe Tyr Pro Gly Ser Gly Ser Ile Lys Tyr Asn Glu Lys Phe Lys
1 5 10 15
Asp
<210> 286
<211> 11
<212> PRT
<213> 小鼠(Mus musculus)
<400> 286
His Glu Val Tyr Tyr Asp Tyr Asp Lys Ser Met
1 5 10
<210> 287
<211> 15
<212> PRT
<213> 小鼠(Mus musculus)
<400> 287
Leu Tyr Ser Ser Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln
1 5 10 15
<210> 288
<211> 7
<212> PRT
<213> 小鼠(Mus musculus)
<400> 288
Trp Ala Ser Thr Arg Glu Ser
1 5
<210> 289
<211> 9
<212> PRT
<213> 小鼠(Mus musculus)
<400> 289
Gln Gln Tyr Tyr Ser Tyr Pro Tyr Thr
1 5
<210> 290
<211> 5
<212> PRT
<213> 小鼠(Mus musculus)
<400> 290
Asn Tyr Leu Ile Glu
1 5
<210> 291
<211> 19
<212> PRT
<213> 小鼠(Mus musculus)
<400> 291
Val Ile Asn Pro Lys Ser Gly Gly Thr Lys Tyr Asn Glu Lys Phe Arg
1 5 10 15
Gly Lys Ala
<210> 292
<211> 11
<212> PRT
<213> 小鼠(Mus musculus)
<400> 292
Thr Gly Thr Asp Tyr Trp Gly Gln Gly Thr Thr
1 5 10
<210> 293
<211> 10
<212> PRT
<213> 小鼠(Mus musculus)
<400> 293
Val Thr Ile Ser Cys Ser Ala Ser Gln Gly
1 5 10
<210> 294
<211> 7
<212> PRT
<213> 小鼠(Mus musculus)
<400> 294
Tyr Thr Ser Ser Leu Arg Ser
1 5
<210> 295
<211> 9
<212> PRT
<213> 小鼠(Mus musculus)
<400> 295
Gln Gln Tyr Ser Lys Leu Pro Arg Thr
1 5
<210> 296
<211> 12
<212> PRT
<213> 人(Homo sapiens)
<400> 296
Phe Thr Ser Gly Glu Lys Glu Gln Val Asp Glu Trp
1 5 10
<210> 297
<211> 16
<212> PRT
<213> 人(Homo sapiens)
<400> 297
Ala Glu Gln Lys Arg Leu Lys Thr Val Leu Glu Leu Gln Tyr Val Leu
1 5 10 15
<210> 298
<211> 16
<212> PRT
<213> 人(Homo sapiens)
<400> 298
Val Glu Arg Val Phe Gln Ser Asn Tyr Phe Asp Ser Thr His Asn His
1 5 10 15
<210> 299
<211> 16
<212> PRT
<213> 人(Homo sapiens)
<400> 299
Phe Gln Ser Met Gln Thr Val Phe Asn Met Asn Ala Pro Val Pro Pro
1 5 10 15
<210> 300
<211> 5
<212> PRT
<213> 小鼠(Mus musculus)
<400> 300
Thr Asn Ala Met Asn
1 5
<210> 301
<211> 17
<212> PRT
<213> 小鼠(Mus musculus)
<400> 301
Arg Ile Arg Ser Lys Ser Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser
1 5 10 15
Val
<210> 302
<211> 11
<212> PRT
<213> 小鼠(Mus musculus)
<400> 302
Asp Trp Asp Gly Phe Leu Tyr Phe Asp Tyr Trp
1 5 10
<210> 303
<211> 112
<212> PRT
<213> 小鼠(Mus musculus)
<400> 303
Gly Gly Gly Leu Val Gln Pro Lys Gly Ser Leu Lys Leu Ser Cys Ala
1 5 10 15
Ala Ser Gly Phe Thr Phe Asn Thr Asn Ala Met Asn Trp Val Arg Gln
20 25 30
Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Ser
35 40 45
Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys Asp Arg Phe Thr
50 55 60
Ile Ser Arg Asp Asp Ser Gln Ser Met Leu Tyr Leu Gln Met Asn Asn
65 70 75 80
Leu Lys Thr Glu Asp Thr Ala Met Tyr Tyr Cys Val Arg Asp Trp Asp
85 90 95
Gly Phe Leu Tyr Phe Asp Tyr Trp Ala Lys His His Leu Thr Leu Phe
100 105 110
<210> 304
<211> 15
<212> PRT
<213> 小鼠(Mus musculus)
<400> 304
Ser Val Ser Thr Ser Gly Tyr Ser Tyr Met His Trp Asn Gln Gln
1 5 10 15
<210> 305
<211> 7
<212> PRT
<213> 小鼠(Mus musculus)
<400> 305
Leu Val Ser Asn Leu Glu Ser
1 5
<210> 306
<211> 9
<212> PRT
<213> 小鼠(Mus musculus)
<400> 306
Gln His Ile Arg Glu Leu Thr Arg Ser
1 5
<210> 307
<211> 104
<212> PRT
<213> 小鼠(Mus musculus)
<400> 307
Thr Gln Ser Pro Ala Ser Leu Ala Val Ser Leu Gly Gln Arg Ala Thr
1 5 10 15
Ile Ser Tyr Arg Ala Ser Lys Ser Val Ser Thr Ser Gly Tyr Ser Tyr
20 25 30
Met His Trp Asn Gln Gln Lys Pro Gly Gln Pro Pro Arg Leu Leu Ile
35 40 45
Tyr Leu Val Ser Asn Leu Glu Ser Gly Val Pro Ala Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Asn Ile His Pro Val Glu Glu
65 70 75 80
Glu Asp Ala Ala Thr Tyr Tyr Cys Gln His Ile Arg Glu Leu Thr Arg
85 90 95
Ser Glu Gly Gly Pro Ser Trp Lys
100
<210> 308
<211> 14
<212> PRT
<213> 人(Homo sapiens)
<400> 308
Pro Pro Val Asn Glu Pro Glu Thr Leu Lys Gln Gln Asn Gln
1 5 10
<210> 309
<211> 12
<212> PRT
<213> 人(Homo sapiens)
<400> 309
Glu Thr Leu Lys Gln Gln Asn Gln Tyr Gln Ala Ser
1 5 10

Claims (14)

1.用于癌的治疗和/或预防的药品,其特征在于,一起包含或各自分开地组合包含:与CAPRIN-1蛋白质具有免疫反应性的抗体或其片段、和拓扑异构酶I抑制剂。
2.根据权利要求1所述的药品,所述拓扑异构酶I抑制剂是拓扑替康或伊立替康。
3.根据权利要求1或2所述的药品,所述抗体或其片段与CAPRIN-1蛋白质具有免疫反应性,所述CAPRIN-1蛋白质具有序列号2~30中任一偶数序列号所示的氨基酸序列、或与该氨基酸序列有80%以上的序列同一性的氨基酸序列。
4.根据权利要求1~3的任一项所述的药品,所述抗体或其片段与在癌细胞表面上存在的CAPRIN-1蛋白质的细胞外区域具有免疫反应性。
5.根据权利要求1~4的任一项所述的药品,所述抗体或其片段与CAPRIN-1蛋白质的部分多肽具有免疫反应性,所述CAPRIN-1蛋白质的部分多肽具有序列号31~35、296~299、308、309的任一项所示的氨基酸序列、或与该氨基酸序列有80%以上的序列同一性的氨基酸序列。
6.根据权利要求1~5的任一项所述的药品,所述抗体是单克隆抗体或多克隆抗体。
7.根据权利要求1~6的任一项所述的药品,所述抗体或其片段是以下(A)~(M)的任一者,
(A)包含重链可变区和轻链可变区、且与CAPRIN-1蛋白质具有免疫反应性的抗体或其片段,所述重链可变区包含序列号36所示的互补决定区CDR1、序列号37所示的互补决定区CDR2、和序列号38所示的互补决定区CDR3,所述轻链可变区包含序列号40所示的互补决定区CDR1、序列号41所示的互补决定区CDR2、和序列号42所示的互补决定区CDR3;
(B)包含重链可变区和轻链可变区、且与CAPRIN-1蛋白质具有免疫反应性的抗体或其片段,所述重链可变区包含序列号44所示的互补决定区CDR1、序列号45所示的互补决定区CDR2、和序列号46所示的互补决定区CDR3,所述轻链可变区包含序列号48所示的互补决定区CDR1、序列号49所示的互补决定区CDR2、和序列号50所示的互补决定区CDR3;
(C)包含重链可变区和轻链可变区、且与CAPRIN-1蛋白质具有免疫反应性的抗体或其片段,所述重链可变区包含序列号52所示的互补决定区CDR1、序列号53所示的互补决定区CDR2、和序列号54所示的互补决定区CDR3,所述轻链可变区包含序列号56所示的互补决定区CDR1、序列号57所示的互补决定区CDR2、和序列号58所示的互补决定区CDR3;
(D)包含重链可变区和轻链可变区、且与CAPRIN-1蛋白质具有免疫反应性的抗体或其片段,所述重链可变区包含序列号60所示的互补决定区CDR1、序列号61所示的互补决定区CDR2、和序列号62所示的互补决定区CDR3,所述轻链可变区包含序列号64所示的互补决定区CDR1、序列号65所示的互补决定区CDR2、和序列号66所示的互补决定区CDR3;
(E)包含重链可变区和轻链可变区、且与CAPRIN-1蛋白质具有免疫反应性的抗体或其片段,所述重链可变区包含序列号170所示的互补决定区CDR1、序列号171所示的互补决定区CDR2、和序列号172所示的互补决定区CDR3,所述轻链可变区包含序列号173所示的互补决定区CDR1、序列号174所示的互补决定区CDR2、和序列号175所示的互补决定区CDR3;
(F)包含重链可变区和轻链可变区、且与CAPRIN-1蛋白质具有免疫反应性的抗体或其片段,所述重链可变区包含序列号176所示的互补决定区CDR1、序列号177所示的互补决定区CDR2、和序列号178所示的互补决定区CDR3,所述轻链可变区包含序列号179所示的互补决定区CDR1、序列号180所示的互补决定区CDR2、和序列号181所示的互补决定区CDR3;
(G)包含重链可变区和轻链可变区、且与CAPRIN-1蛋白质具有免疫反应性的抗体或其片段,所述重链可变区包含序列号182所示的互补决定区CDR1、序列号183所示的互补决定区CDR2、和序列号184所示的互补决定区CDR3,所述轻链可变区包含序列号185所示的互补决定区CDR1、序列号186所示的互补决定区CDR2、和序列号187所示的互补决定区CDR3;
(H)包含重链可变区和轻链可变区、且与CAPRIN-1蛋白质具有免疫反应性的抗体或其片段,所述重链可变区包含序列号188所示的互补决定区CDR1、序列号189所示的互补决定区CDR2、和序列号190所示的互补决定区CDR3,所述轻链可变区包含序列号191所示的互补决定区CDR1、序列号192所示的互补决定区CDR2、和序列号193所示的互补决定区CDR3;
(I)包含重链可变区和轻链可变区、且与CAPRIN-1蛋白质具有免疫反应性的抗体或其片段,所述重链可变区包含序列号146所示的互补决定区CDR1、序列号147所示的互补决定区CDR2、和序列号148所示的互补决定区CDR3,所述轻链可变区包含序列号149所示的互补决定区CDR1、序列号150所示的互补决定区CDR2、和序列号151所示的互补决定区CDR3;
(J)包含重链可变区和轻链可变区、且与CAPRIN-1蛋白质具有免疫反应性的抗体或其片段,所述重链可变区包含序列号272所示的互补决定区CDR1、序列号273所示的互补决定区CDR2、和序列号274所示的互补决定区CDR3,所述轻链可变区包含序列号275所示的互补决定区CDR1、序列号276所示的互补决定区CDR2、和序列号277所示的互补决定区CDR3;
(K)包含重链可变区和轻链可变区、且与CAPRIN-1蛋白质具有免疫反应性的抗体或其片段,所述重链可变区包含序列号290所示的互补决定区CDR1、序列号291所示的互补决定区CDR2、和序列号292所示的互补决定区CDR3,所述轻链可变区包含序列号293所示的互补决定区CDR1、序列号294所示的互补决定区CDR2、和序列号295所示的互补决定区CDR3;
(L)包含重链可变区和轻链可变区、且与CAPRIN-1蛋白质具有免疫反应性的抗体或其片段,所述重链可变区包含序列号301所示的互补决定区CDR1、序列号302所示的互补决定区CDR2、和序列号303所示的互补决定区CDR3,所述轻链可变区包含序列号305所示的互补决定区CDR1、序列号306所示的互补决定区CDR2、和序列号307所示的互补决定区CDR3;
(M)包含重链可变区和轻链可变区、且与CAPRIN-1蛋白质具有免疫反应性的抗体或其片段,所述重链可变区包含序列号134所示的互补决定区CDR1、序列号135所示的互补决定区CDR2、和序列号136所示的互补决定区CDR3,所述轻链可变区包含序列号137所示的互补决定区CDR1、序列号138所示的互补决定区CDR2、和序列号139所示的互补决定区CDR3。
8.根据权利要求1~7的任一项所述的药品,所述抗体或其片段是以下(a)~(al)的任一者,
(a)重链可变区包含序列号39的氨基酸序列、且轻链可变区包含序列号43的氨基酸序列的抗体或其片段;
(b)重链可变区包含序列号47的氨基酸序列、且轻链可变区包含序列号51的氨基酸序列的抗体或其片段;
(c)重链可变区包含序列号55的氨基酸序列、且轻链可变区包含序列号59的氨基酸序列的抗体或其片段;
(d)重链可变区包含序列号63的氨基酸序列、且轻链可变区包含序列号67的氨基酸序列的抗体或其片段;
(e)重链可变区包含序列号68的氨基酸序列、且轻链可变区包含序列号69的氨基酸序列的抗体或其片段;
(f)重链可变区包含序列号70的氨基酸序列、且轻链可变区包含序列号71的氨基酸序列的抗体或其片段;
(g)重链可变区包含序列号72的氨基酸序列、且轻链可变区包含序列号73的氨基酸序列的抗体或其片段;
(h)重链可变区包含序列号74的氨基酸序列、且轻链可变区包含序列号75的氨基酸序列的抗体或其片段;
(i)重链可变区包含序列号76的氨基酸序列、且轻链可变区包含序列号77的氨基酸序列的抗体或其片段;
(j)重链可变区包含序列号78的氨基酸序列、且轻链可变区包含序列号79的氨基酸序列的抗体或其片段;
(k)重链可变区包含序列号80的氨基酸序列、且轻链可变区包含序列号81的氨基酸序列的抗体或其片段;
(l)重链可变区包含序列号82的氨基酸序列、且轻链可变区包含序列号83的氨基酸序列的抗体或其片段;
(m)重链可变区包含序列号84的氨基酸序列、且轻链可变区包含序列号85的氨基酸序列的抗体或其片段;
(n)重链可变区包含序列号86的氨基酸序列、且轻链可变区包含序列号87的氨基酸序列的抗体或其片段;
(o)重链可变区包含序列号88的氨基酸序列、且轻链可变区包含序列号89的氨基酸序列的抗体或其片段;
(p)重链可变区包含序列号90的氨基酸序列、且轻链可变区包含序列号91的氨基酸序列的抗体或其片段;
(q)重链可变区包含序列号92的氨基酸序列、且轻链可变区包含序列号93的氨基酸序列的抗体或其片段;
(r)重链可变区包含序列号94的氨基酸序列、且轻链可变区包含序列号95的氨基酸序列的抗体或其片段;
(s)重链可变区包含序列号96的氨基酸序列、且轻链可变区包含序列号97的氨基酸序列的抗体或其片段;
(t)重链可变区包含序列号98的氨基酸序列、且轻链可变区包含序列号99的氨基酸序列的抗体或其片段;
(u)重链可变区包含序列号100的氨基酸序列、且轻链可变区包含序列号101的氨基酸序列的抗体或其片段;
(v)重链可变区包含序列号102的氨基酸序列、且轻链可变区包含序列号103的氨基酸序列的抗体或其片段;
(w)重链可变区包含序列号104的氨基酸序列、且轻链可变区包含序列号105的氨基酸序列的抗体或其片段;
(x)重链可变区包含序列号106的氨基酸序列、且轻链可变区包含序列号107的氨基酸序列的抗体或其片段;
(y)重链可变区包含序列号108的氨基酸序列、且轻链可变区包含序列号109的氨基酸序列的抗体或其片段;
(z)重链可变区包含序列号110的氨基酸序列、且轻链可变区包含序列号111的氨基酸序列的抗体或其片段;
(aa)重链可变区包含序列号112的氨基酸序列、且轻链可变区包含序列号113的氨基酸序列的抗体或其片段;
(ab)重链可变区包含序列号114的氨基酸序列、且轻链可变区包含序列号115的氨基酸序列的抗体或其片段;
(ac)重链可变区包含序列号116的氨基酸序列、且轻链可变区包含序列号117的氨基酸序列的抗体或其片段;
(ad)重链可变区包含序列号118的氨基酸序列、且轻链可变区包含序列号119的氨基酸序列的抗体或其片段;
(ae)重链可变区包含序列号120的氨基酸序列、且轻链可变区包含序列号121的氨基酸序列的抗体或其片段;
(af)重链可变区包含序列号122的氨基酸序列、且轻链可变区包含序列号123的氨基酸序列的抗体或其片段;
(ag)重链可变区包含序列号124的氨基酸序列、且轻链可变区包含序列号125的氨基酸序列的抗体或其片段;
(ah)重链可变区包含序列号126的氨基酸序列、且轻链可变区包含序列号127的氨基酸序列的抗体或其片段;
(ai)重链可变区包含序列号128的氨基酸序列、且轻链可变区包含序列号129的氨基酸序列的抗体或其片段;
(aj)重链可变区包含序列号130的氨基酸序列、且轻链可变区包含序列号131的氨基酸序列的抗体或其片段;
(ak)重链可变区包含序列号132的氨基酸序列、且轻链可变区包含序列号133的氨基酸序列的抗体或其片段;
(al)重链可变区包含序列号300的氨基酸序列、且轻链可变区包含序列号304的氨基酸序列的抗体或其片段。
9.根据权利要求1~8的任一项所述的药品,所述抗体是人抗体、人源化抗体、嵌合抗体或单链抗体。
10.根据权利要求1~9的任一项所述的药品,所述癌是在细胞膜表面表达CAPRIN-1蛋白质的癌。
11.根据权利要求1~10的任一项所述的药品,所述癌是卵巢癌、胆管癌、乳癌、肾癌、胰癌、大肠癌、黑素瘤、肺癌、肾细胞癌、霍奇金淋巴瘤、头颈癌、胃癌、间皮癌、结肠/直肠癌、食道癌、食管胃结合部癌、肝细胞癌、胶质母细胞瘤、尿路上皮癌、膀胱癌、子宫癌、原发性中枢神经系统淋巴瘤、原发性睾丸淋巴瘤、胆道癌、脑肿瘤、前列腺癌、白血病、淋巴瘤、肝癌、肉瘤、纤维肉瘤、肥大细胞瘤、肾上腺皮质癌、尤因肉瘤、多发性骨髓瘤、睾丸癌、甲状腺癌、基底细胞癌、佩吉特病或皮肤癌。
12.癌的治疗和/或预防用药物组合物的药效增强剂,所述癌的治疗和/或预防用药物组合物以与CAPRIN-1蛋白质具有免疫反应性的抗体或其片段作为有效成分,所述药效增强剂以拓扑异构酶I抑制剂作为有效成分。
13.癌的治疗和/或预防用药物组合物的药效增强剂,所述癌的治疗和/或预防用药物组合物以拓扑异构酶I抑制剂作为有效成分,所述药效增强剂以与CAPRIN-1蛋白质具有免疫反应性的抗体或其片段作为有效成分。
14.用于癌的治疗和/或预防的方法,其特征在于,将与CAPRIN-1蛋白质具有免疫反应性的抗体或其片段、和拓扑异构酶I抑制剂一起或各自分开地施与受检者。
CN202280041252.1A 2021-06-23 2022-06-22 用于癌的治疗和/或预防的药品 Pending CN117460532A (zh)

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