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CN107126560A - 通过使用抗骨硬化蛋白抗体治疗牙槽骨流失的方法 - Google Patents

通过使用抗骨硬化蛋白抗体治疗牙槽骨流失的方法 Download PDF

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CN107126560A
CN107126560A CN201710477474.9A CN201710477474A CN107126560A CN 107126560 A CN107126560 A CN 107126560A CN 201710477474 A CN201710477474 A CN 201710477474A CN 107126560 A CN107126560 A CN 107126560A
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柯华珠
刘敏
W·V·格兰诺拜尔
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University of Michigan Ann Arbor
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Abstract

本发明涉及一种通过使用抗骨硬化蛋白抗体治疗牙槽骨流失的方法。具体而言,本发明提供一种治疗牙槽骨流失的方法,所述方法包括向有需要的受试者施用骨硬化蛋白抑制剂。

Description

通过使用抗骨硬化蛋白抗体治疗牙槽骨流失的方法
本申请是申请号为201280064888.4、申请日为2012年12月11日、发明名称为“通过使用抗骨硬化蛋白抗体治疗牙槽骨流失的方法”的发明专利申请的分案申请。
相关申请的交叉引用
本申请要求2011年12月28曰提交的美国临时申请第61/580,964号的优先权益。所述优先权申请的公开内容以全文引用的方式并入本文中。
发明技术领域
本发明总体上涉及使用骨硬化蛋白抑制剂治疗牙槽骨流失的方法。
以电子方式提交的材料的引入并入
以全文引用的方式并入的是与此同时提交且鉴别如下的计算机可读核苷酸/氨基酸序列表:ASCII(文本)文件名称“46570_SeqListing.txt”,805,989个字节,2012年12月7曰创建。
以引用方式并入
以下申请特此以全文引用的方式并入:2006年4月25曰提交的美国专利申请第11/410,540号,其要求2006年4月17曰提交的美国临时专利申请第60/792,645号、2006年3月13日提交的美国临时专利申请第60/782,244号、2006年2月24日提交的美国临时专利申请第60/776,847号以及2005年5月3日提交的美国临时专利申请第60/677,583号的优先权;以及2006年4月25日提交的美国专利申请第11/411,003号(以美国专利第7,592,429号颁布),其要求2006年4月17日提交的美国临时专利申请第60/792,645号、2006年3月13日提交的美国临时专利申请第60/782,244号、2006年2月24日提交的美国临时专利申请第60/776,847号以及2005年5月3日提交的美国临时专利申请第60/677,583号的优先权。以下申请特此也以引用的方式并入:2008年9月17日提交的美国专利申请第12/212,327号,其要求2007年9月17日提交的美国临时专利申请第60/973,024号的优先权;以及2010年6月29日提交的美国专利申请第12/811,171号,其根据美国法典第35篇371条为2008年12月15日提交的国际专利申请第PCT/US08/86864号的美国国家阶段申请,其要求2007年12月14日提交的美国临时专利申请第61/013,917号的优先权。
背景技术
已知牙周感染和牙龈发炎为牙周疾病的主要原因。两者皆为慢性发炎性疾病,且随着其进展,牙周组织损坏且牙槽骨因在一些状况下引起牙齿支撑物损失的骨吸收而减少。另外,牙槽骨可能因由外科治疗引起的穿孔或所进展的龋齿的顶端病变而变得缺损。
发明内容
本发明是针对使用骨硬化蛋白抑制剂来增强牙槽骨的方法。在一方面,本文描述一种治疗受试者牙槽骨流失的方法,所述方法包括施用有效减小牙骨质-牙轴质接面与牙槽骨嵴之间的距离的量的骨硬化蛋白抑制剂(例如抗骨硬化蛋白抗体或抗体片段),剂量任选地为每周约5mg至约1,000mg。在一个实施方案中,在整个治疗期内,每周两次施用骨硬化蛋白抑制剂。在另一实施方案中,在整个治疗期内,每周一次施用骨硬化蛋白抑制剂。
治疗期可为至少约1周、2周、3周、4周、5周、6周、7周、8周、9周、10周、11周、12周、3个月、13周、14周、15周、16周、4个月、17周、18周、19周、20周、5个月、21周、22周、23周、24周、6个月、25周、26周、27周、28周、7个月、29周、30周、31周或更长(例如8个月、9个月、10个月、11个月、1年、15个月、18个月或更长)。在一些实施方案中,治疗期为约6-12周。在一些实施方案中,治疗期为4-12周或约1-3个月。在一些实施方案中,治疗期为约12-20周或约3-5个月。在一些实施方案中,治疗期为约20-32周或约5-8个月。在一些实施方案中,治疗期为约24-36周或约6-9个月。在一些实施方案中,治疗期至多为约28周。在一些实施方案中,治疗期为约1年。在一些或任何实施方案中,治疗期至多为约18个月。
在一些或任何实施方案中,截至治疗开始后六周,与治疗前距离相比,牙骨质-牙轴质接面与牙槽骨嵴之间的距离减小了至少10%(例如至少10%、至少20%、至少30%、至少40%、至少50%、至少60%、至少70%、至少80%、至少90%或更多)。在一些或任何实施方案中,截至治疗开始后六周,与对照受试者(即不接受骨硬化蛋白抑制剂治疗的晚期牙周病受试者)相比,牙骨质-牙轴质接面与牙槽骨嵴之间的距离减小了至少10%(例如至少10%、至少20%、至少30%、至少40%、至少50%、至少60%、至少70%、至少80%、至少90%或更多)。在一些实施方案中,截至治疗开始后六周,牙骨质-牙轴质接面与牙槽骨嵴之间的距离恢复至疾病前状态。在一些实施方案中,截至治疗开始后六周,牙骨质-牙轴质接面与牙槽骨嵴之间的距离小于或等于约2mm(例如约2mm、约1.9mm、约1.8mm、约1.7mm、约1.6mm、约1.5mm、约1.4mm、约1.3mm、约1.2mm、约1.1mm或约1mm)。
在一些或任何实施方案中,截至治疗开始后六周,与治疗前牙槽骨高度相比,牙槽骨高度增加了至少10%(例如至少10%、至少20%、至少30%、至少40%、至少50%、至少60%、至少70%、至少80%、至少90%或更多)。在一些或任何实施方案中,截至治疗开始后六周,与对照受试者(即不接受骨硬化蛋白抑制剂治疗的晚期牙周病受试者)相比,牙槽骨高度增加了至少10%(例如至少10%、至少20%、至少30%、至少40%、至少50%、至少60%、至少70%、至少80%、至少90%或更多)。在一些实施方案中,截至治疗开始后六周,牙槽骨高度恢复至牙槽骨高度的疾病前状态。
在一些或任何实施方案中,截至治疗开始后六周,与治疗前牙槽骨高度相比或与对照受试者(即不接受骨硬化蛋白抑制剂治疗的晚期牙周病受试者)相比,牙槽骨高度增加了至少0.1mm(例如至少约0.1mm、约0.2mm、约0.3mm、约0.4mm、约0.5mm、约0.6mm、约0.7mm、约0.8mm、约0.9mm、约1mm、约1.5mm、约2mm、约2.5mm、约3mm、约3.5mm、约4mm、约4.5mm、约5mm、约5.5mm、约6mm、约6.5mm、约7mm、约7.5mm、约8mm、约8.5mm、约9mm、约9.5或约10mm)或更多。
在一些或任何实施方案中,截至治疗开始后六周,与治疗前牙槽骨密度相比或与对照受试者(即不接受骨硬化蛋白抑制剂治疗的晚期牙周病受试者)相比,牙槽骨密度增加了至少10%(例如至少10%、至少20%、至少30%、至少40%、至少50%、至少60%、至少70%、至少80%、至少90%或更多)。在一些实施方案中,截至治疗开始后六周,牙槽骨密度恢复至疾病前状态。
在一些或任何实施方案中,截至治疗开始后六周,与治疗前牙槽骨体积分数(BVF)相比或与对照受试者(即不接受骨硬化蛋白抑制剂治疗的晚期牙周病受试者)相比,牙槽BVF增加了至少10%(例如至少10%、至少20%、至少30%、至少40%、至少50%、至少60%、至少70%、至少80%、至少90%或更多)。
在一些或任何实施方案中,本文所述的方法可以进一步包括在施用骨硬化蛋白抑制剂(例如抗骨硬化蛋白抗体或抗体片段)之前测量牙槽骨的骨骼矿物密度以鉴别需要用骨硬化蛋白抑制剂治疗的受试者。牙槽骨密度测量值小于约750亨斯菲尔德单位(Hounsfield Unit)(例如为约750HU、约700HU、约650HU、约600HU、约550HU、约500HU、约450HU、约400HU或更小)的受试者被鉴别为需要用抗骨硬化蛋白抗体或抗体片段治疗的受试者。
本文所述的方法治疗的牙槽骨流失包括但不限于与以下状况相关的牙槽骨流失:牙周炎(例如晚期牙周病)、牙齿损失、拔牙、戴假牙、口腔外科、骨髓炎、放射性骨坏死、发育畸形(例如出生时缺陷,如牙齿、面颅骨或颌的缺失部分)、窦不足、未对准、或外伤(例如牙齿撕脱或颌骨折)。在一些实施方案中,欲治疗的受试者患有晚期牙周炎。
在一些实施方案中,牙槽骨流失因去除含有肿瘤(例如良性肿瘤)的骨骼部分而产生。示例性良性骨肿瘤包括但不限于骨瘤、骨样骨瘤、骨母细胞瘤、骨软骨瘤、内生软骨瘤、软骨粘液样纤维瘤、动脉瘤样骨囊肿、单房性骨囊肿、骨纤维性发育异常及骨骼巨细胞瘤。
在一些或任何实施方案中,施用骨硬化蛋白抑制剂(例如抗骨硬化蛋白抗体或抗体片段),并且组合使用支持骨骼的再生长的材料,所述材料如骨移植物、骨粉、骨碎片、去矿化骨基质、骨骼支架、修复体、金属稳定剂或骨骼支架物质,包括一或多种聚合物、陶瓷、牙骨质及基于磷酸钙的骨骼移植物取代物。本领域中已知所述材料的许多变化形式。
在一些或任何实施方案中,所述方法包括在施用骨硬化蛋白抑制剂(例如抗骨硬化蛋白抗体或抗体片段)之前向受试者施用用于治疗牙周病的标准护理疗法。例如,在一些实施方案中,用于治疗牙周病的标准护理疗法为治疗剂,包括但不限于和/或化学改性的四环素-3(CMT-3)。在一些实施方案中,标准护理疗法包括口冲洗法和/或刮牙术以及受试者感染区域的牙龈上和/或牙龈下清创术(例如去除微生物牙菌斑和牙垢)。在一些实施方案中,标准护理包括在施用骨硬化蛋白抑制剂之前进行口冲洗法和/或刮牙术以及感染区域清创术与Periostat和/或CMT-3的组合。在一些实施方案中,所述方法包括与施用骨硬化蛋白抑制剂并行施用标准护理疗法。在其它实施方案中,标准护理疗法相继施用。例如,标准护理疗法可在向受试者施用骨硬化蛋白抑制剂之前1天、2天、3天、4天、5天、6天、1周、2周、3周、4周、6周、8周、10周、12周或更长时间来施用。在优选实施方案中,在施用骨硬化蛋白抑制剂之前,受试者的牙周病进展减缓、停止或逆转。
在一些或任何实施方案中,所述方法进一步包含施用抗生素,如选自由以下组成的组的抗生素:阿莫西林(amoxicillin)、盐酸四环素、多西环素(doxycycline)、米诺霉素、阿奇霉素(azithromycin)、罗红霉素、莫西沙星(moxifloxacin)、环丙沙星以及甲硝哒唑。在一些实施方案中,所述方法包括在向受试者施用骨硬化蛋白抑制剂之前或施用之后向受试者施用抗生素。在其它实施方案中,所述方法包括与施用骨硬化蛋白抑制剂并行向受试者施用抗生素。
在一些或任何实施方案中,所述方法进一步包括施用第二骨骼增强治疗剂以治疗骨骼矿物密度减小或骨折。本领域中已知许多此类型的治疗剂。在一些实施方案中,骨骼增强治疗剂选自由以下各物组成的组:抗再吸收药物、成骨剂、雌激素受体调节剂(包括但不限于雷诺昔芬(raloxifene)、巴多昔芬(bazedoxifene)以及拉索昔芬(lasofoxifene))以及对破骨细胞具有抑制作用的药物。在一些实施方案中,第二骨骼增强剂选自由以下组成的组:双膦酸盐(包括但不限于阿仑膦酸钠(alendronate sodium;)、利塞膦酸盐(risedronate)、伊班膦酸钠(ibandronate sodium;)以及唑来膦酸(zoledronic acid;))、雌激素或雌激素类似物、钙来源、替勃龙(Tibolone)、降钙素、骨化三醇以及激素替代疗法。在一些实施方案中,第二骨骼增强剂包括但不限于副甲状腺素(PTH)或其肽片段、PTH相关蛋白质(PTHrp)、骨骼形态发生蛋白、成骨素、NaF、PGE2激动剂、士他汀(statin)、抗DKK1抗体或抑制剂、抗RANK配体(RANKL)抗体(例如)或RANKL抑制剂、雷奈酸锶(strontium ranelate)、维生素D、或维生素D衍生物或其模拟物。在一些实施方案中,第二骨骼增强剂为(特立帕肽(Teriparatide)或重组人副甲状腺素类似物(1-34))或(副甲状腺素)。在一些或任何实施方案中,骨骼增强剂为
在一些实施方案中,与骨硬化蛋白抑制剂(例如,持续治疗期内一段时间)并行施用第二骨骼增强剂。在其它实施方案中,一旦骨硬化蛋白抑制剂治疗期结束,就施用第二骨骼增强剂持续一段时间(即,持续一段维持期)。在此类实施方案中,施用第二骨骼增强剂持续约1周至约5年的一段维持期。
所述方法可以进一步包括随后施用一或多个有效维持骨骼矿物密度的量的骨硬化蛋白抑制剂,维持期任选地为在治疗期结束后至少约12周、6个月、1年、2年、3年、4年、5年或更长时间(例如受试者一生)。
牙周病治疗计划还可包括积极治疗完成后的支持性跟踪疗法。支持性跟踪疗法包括但不限于机械清创术、口腔卫生增强(例如定期专业清洁、日常刷洗及清牙垢)以及施用抗生素。
在任何本文公开的实施方案中,骨硬化蛋白抑制剂任选地为骨硬化蛋白结合剂(例如抗骨硬化蛋白抗体或抗体片段)。尤其涵盖美国专利公布号2007/0110747中所公开的骨硬化蛋白结合剂在本文公开的任何方法中的使用或用于制备根据本文公开的任何方法施用的药剂的用途。一个或多个剂量的骨硬化蛋白抑制剂以可有效治疗牙槽骨流失的一定量和一段时间来施用。在不同实施方案中,每周向受试者(例如人受试者)施用包含约50毫克至约1,000毫克骨硬化蛋白抑制剂的一个或多个剂量。例如,骨硬化蛋白抑制剂(例如抗骨硬化蛋白抗体或抗体片段)的剂量可包含至少约5mg、15mg、25mg、50mg、约60mg、约70mg、约80mg、约90mg、约100mg、约120mg、约150mg、约200mg、约240mg、约250mg、约280mg、约300mg、约350mg、约400mg、约420mg、约450mg、约500mg、约550mg、约600mg、约650mg、约700mg、约750mg、约800mg、约850mg、约900mg、约950mg或高达约1,000mg的骨硬化蛋白抑制剂。还涵盖任何和所有这些终点之间的范围,例如约50mg至约80mg、约70mg至约140mg、约75mg至约100mg、约100mg至约150mg、约140mg至约210mg、或约150mg至约200mg、或约280至约410mg。剂量以任何间隔施用,如一周多次(例如每周两次或三次)、每周一次、每两周一次、每三周一次,或每四周一次。在一些或任何实施方案中,每周两次施用约120mg至约210mg范围内的剂量的骨硬化蛋白抑制剂(例如抗骨硬化蛋白抗体或抗体片段)。在一些或任何实施方案中,每周两次施用约140mg的剂量的骨硬化蛋白抑制剂(例如抗骨硬化蛋白抗体或抗体片段)。
在一些实施方案中,所述一或多个剂量的骨硬化蛋白抑制剂可以包含每公斤体重约0.1与约50毫克之间(例如约5与约50毫克之间)、或约1至约100毫克(mg/kg)的骨硬化蛋白抑制剂。例如,骨硬化蛋白抑制剂(例如抗骨硬化蛋白抗体或抗体片段)的剂量可以包含至少约0.1mg/kg、0.5mg/kg、1mg/kg、约2mg/kg、约3mg/kg、约4mg/kg、约5mg/kg、约6mg/kg、约7mg/kg、约8mg/kg、约9mg/kg、约10mg/kg、约20mg/kg、约25mg/kg、约26mg/kg、约27mg/kg、约28mg/kg、约29mg/kg、约30mg/kg、约31mg/kg、约32mg/kg、约33mg/kg、约34mg/kg、约35mg/kg、约36mg/kg、约37mg/kg、约38mg/kg、约39mg/kg、约40mg/kg、约41mg/kg、约42mg/kg、约43mg/kg、约44mg/kg、约45mg/kg、约46mg/kg、约47mg/kg、约48mg/kg、或约49mg/kg、或约50mg/kg、约55mg/kg、约60mg/kg、约65mg/kg、约70mg/kg、约75mg/kg、约80mg/kg、约85mg/kg、约90mg/kg、约95mg/kg、或高达约100mg/kg。还涵盖任何和所有这些终点之间的范围,例如约1mg/kg至约3mg/kg、约1mg/kg至约5mg/kg、约1mg/kg至约10mg/kg、约1mg/kg至约20mg/kg、约1mg/kg至约40mg/kg、约5mg/kg至约30mg/kg、或约5mg/kg至约20mg/kg。
本文还描述有效量的抗骨硬化蛋白抑制剂用于治疗受试者牙槽骨流失的用途,所述抗骨硬化蛋白抑制剂是例如按上述任何量,如每周约50mg至约1,000mg,其中在一段治疗期内进行骨硬化蛋白结合剂的一次或多次施用,所述治疗期持续至少1周、2周、3周、4周、5周、6周、7周、8周、9周、10周、11周、12周、3个月、13周、14周、15周、16周、4个月、17周、18周、19周、20周、5个月、21周、22周、23周、24周、6个月、25周、26周、27周、28周、7个月、29周、30周、31周或更长时间(例如8个月、9个月、10个月、11个月、1年、15个月、18个月或更长时间)。
在一些或任何实施方案中,皮下施用骨硬化蛋白抑制剂。在其它实施方案中,对受试者颌局部施用骨硬化蛋白抑制剂。在一些或任何实施方案中,对受试者的患病牙龈区域局部施用骨硬化蛋白抑制剂。在一些或任何实施方案中,对受试者牙周袋施用骨硬化蛋白抑制剂。
骨硬化蛋白抑制剂(例如抗骨硬化蛋白抗体或抗体片段)还可用于制备使用本文所述的任何给药和/或时机方案施用给牙槽骨流失受试者的药剂。因此,本发明还涵盖根据本文所述的任何给药和/或时机方案使用的骨硬化蛋白抑制剂。任选地,骨硬化蛋白抑制剂存在于容器中,如单次剂量或多次剂量小瓶或注射器。本发明包括一种包含抗骨硬化蛋白抗体或其片段以及根据本文所述的任何给药和/或时机方案施用抗体或其片段以治疗牙槽骨流失的说明书的容器。
在不同实施方案中,骨硬化蛋白抑制剂为骨硬化蛋白结合剂,例如抗骨硬化蛋白抗体或抗体片段。任选地,所述抗骨硬化蛋白抗体或抗体片段交叉封闭以下抗体中至少一者与骨硬化蛋白的结合:Ab-A、Ab-B、Ab-C、Ab-D、Ab-1、Ab-2、Ab-3、Ab-4、Ab-5、Ab-6、Ab-7、Ab-8、Ab-9、Ab-10、Ab-11、Ab-12、Ab-13、Ab-14、Ab-15、Ab-16、Ab-17、Ab-18、Ab-19、Ab-20、Ab-21、Ab-22、Ab-23以及Ab-24,和/或被以下抗体中至少一者交叉封闭与骨硬化蛋白的结合:Ab-A、Ab-B、Ab-C、Ab-D、Ab-1、Ab-2、Ab-3、Ab-4、Ab-5、Ab-6、Ab-7、Ab-8、Ab-9、Ab-10、Ab-11、Ab-12、Ab-13、Ab-14、Ab-15、Ab-16、Ab-17、Ab-18、Ab-19、Ab-20、Ab-21、Ab-22、Ab-23以及Ab-24。
在一些实施方案中,所述抗骨硬化蛋白抗体包含SEQ ID NO:245的CDR-H1、SEQ IDNO:246的CDR-H2、SEQ ID NO:247的CDR-H3、SEQ ID NO:78的CDR-L1、SEQ ID NO:79的CDR-L2、以及SEQ ID NO:80的CDR-L3。
在一个实施方案中,所述抗骨硬化蛋白抗体包含含SEQ ID NO:378的重链以及含SEQ ID NO:376的轻链。在另一实施方案中,抗骨硬化蛋白抗体具有SEQ ID NO:145或SEQID NO:392的重链以及SEQ ID NO:141的轻链。
在另一实施方案中,抗骨硬化蛋白抗体包含国际专利公布号WO2008/115732的SEQID NO:20-25的CDR(SEQ ID NO:416-421)、国际专利公布号WO 2008/115732的SEQ ID NO:26-31的CDR(SEQ ID NO:422-427)、国际专利公布号WO 2008/115732的SEQ ID NO:32-37的CDR(SEQ ID NO:428-433)或国际专利公布号WO 2009/047356的SEQ ID NO:4、15、26、37、48以及59的CDR(分别为SEQ ID NO:443、454、465、476、487以及498)。在另一实施方案中,抗骨硬化蛋白抗体包含国际专利公布号WO 2010/130830的SEQ ID NO:135-143、153-161或171-179中的至少一者的氨基酸序列(分别为SEQ ID NO:745-753、763-771、781-789)。
还涵盖包含本文所述的抗骨硬化蛋白抗体(或抗体片段)的牙齿植入物、基质、凝胶剂以及伤口敷料。在一些实施方案中,牙齿植入物、基质、凝胶剂以及伤口敷料用抗骨硬化蛋白抗体(或抗体片段)涂布。在其它实施方案中,抗骨硬化蛋白抗体(或抗体片段)与本文所述的载体一起配制且施加至目标区域(即受试者的患病牙龈区域或患病牙周袋),任选地在施加牙齿植入物、基质或伤口敷料之前(或之后)。抗骨硬化蛋白抗体(或抗体片段)可通过本领域已知的任何方式施加。在一些实施方案中,在施加牙齿植入物、基质或伤口敷料之前,通过皮下注射向目标区域施用骨硬化蛋白抗体(或抗体片段)。在其它实施方案中,在施加牙齿植入物、基质或伤口敷料之前,通过刷涂或以其它方式涂布受感染区域向受感染区域施用骨硬化蛋白抗体(或抗体片段)。
另外,尤其涵盖抗骨硬化蛋白抗体(或抗体片段)在本文公开的任何方法中的用途或用于制备根据本文公开的任何方法施用的药剂的用途。在此方面,本发明包括一种用于在治疗受试者牙槽骨流失的方法中使用的抗骨硬化蛋白抗体,所述方法包括施用有效减小牙骨质-牙轴质接面与牙槽骨嵴之间的距离的量的抗骨硬化蛋白抗体(或抗体片段),剂量任选地为每周约5mg至约1,000mg。
本发明还包括抗骨硬化蛋白抗体(或抗体片段)的用途,其用于制备供治疗受试者牙槽骨流失用的药剂,其量有效减小牙骨质-牙轴质接面与牙槽骨嵴之间的距离,其中所述抗骨硬化蛋白抗体(或抗体片段)的剂量任选地为每周约5mg至约1,000mg。
上述概述不意欲限定本发明的每个方面,并且在其它部分(如详述)中描述了其它方面。整个文件意欲作为统一的公开内容联系起来,且应理解涵盖本文所述的特征的所有组合,即使特征的组合未能在此文件的同一句子或段落或部分中找到。就本发明的用“一(a或an)”描述或要求的方面来说,应理解除非上下文明显地需要更具限制性的含义,否则这些术语意指“一个或多个”。除非上下文明显地需要其它意思,否则术语“或”应理解涵盖替代性项目或联合项目。如果本发明的方面描述为“包含”特征,则还涵盖实施方案“由所述特征组成”或“基本上由所述特征组成”。
附图说明
图1为列出本文所述的不同抗骨硬化蛋白抗体的氨基酸序列和氨基酸序列的序列标识符的图表。序列标识符指同时提交的序列表中所提供的氨基酸序列。氨基酸序列还阐述于美国专利公布号2007/0110747或国际专利公布号WO 2008/115732、WO 2009/047356或WO 2010/130830中,所述公布特此以引用的方式并入。
图2A和2B为描绘实验牙周炎期间全身性施用抗骨硬化蛋白抗体对骨骼体积分数(图2A)和骨骼矿物密度(图2B)的作用(2周及4周研究终点时进行测量)的曲线。
图3A和3B为描绘实验牙周炎诱发之后全身性施用抗骨硬化蛋白抗体对骨骼体积分数(图3A)和骨骼矿物密度(图3B)的作用(4周、7周以及10周研究终点时进行测量)的曲线。
图4A和4C为描绘实验牙周炎诱发后施用抗骨硬化蛋白抗体对牙骨质-牙轴质接面与骨骼嵴之间的距离的作用(图4A)以及7周(图4B)和10周(图4C)时上颌第二磨牙的位点特异性测量的曲线。
发明详述
本发明至少部分地基于如下发现:骨硬化蛋白抑制剂可治疗与例如牙周病相关的牙槽骨流失。在此方面,本发明提供一种治疗牙槽骨流失的方法。所述方法包括在治疗期期间以有效减小牙骨质-牙轴质接面与牙槽骨嵴之间的距离的量向受试者(例如哺乳动物,如人)施用一个或多个剂量的骨硬化蛋白抑制剂,如骨硬化蛋白结合剂(例如抗骨硬化蛋白抗体或抗体片段)。本发明的材料和方法优于现有疗法,所述现有疗法的治疗功效依赖于侵袭性手术方法(例如骨移植物)来将受试者牙槽骨恢复至疾病前状况(例如高度和/或密度和/或三维骨骼质量)。
通过本文所述的方法治疗的牙槽骨流失包括但不限于与以下状况相关的牙槽骨流失:牙周炎、牙齿损失、拔牙、戴假牙、口腔外科、骨髓炎、放射性骨坏死、发育畸形(例如出生时缺陷,如牙齿、面颅骨或颌的缺失部分)、窦不足、未对准、或外伤(例如牙齿撕脱或颌骨折)。在一些实施方案中,欲治疗的受试者患有晚期牙周炎。
如本文所用的术语“牙周病”意欲涵盖一系列临床病状。牙周病的临床诊断基于视觉和放射照相评价牙周组织并且基于牙齿与牙龈之间的间隙的测量。在人中,这些间隙的深度通常为1-3mm,并且在支撑结缔组织与骨骼损失时加深。在综合临床检查期间,在每个牙齿周围的不同位置(例如4-6个位置)处测量袋深度和组织支撑物,并且记录牙菌斑、牙垢、牙龈出血以及分泌液的量。牙齿放射照相通常用于评估牙齿骨骼支撑物的量。
牙周病的严重性通常基于由牙骨质-牙轴质接面或顶边缘测量的临床附着损失(CAL),且可被视为轻度(1-2mm)、中度(3-4mm)、或重度(≥5mm)。术语“临床附着损失”(CAL)是指牙骨质-牙轴质接面(即顶边缘)至顶端牙龈缘的距离(以毫米测量)。牙周病的特征也可在于袋探测深度,其中轻度疾病的特征在于牙周袋探测深度为约4-5mm,中度疾病的特征在于袋探测深度为约6-7mm,并且重度疾病的特征在于袋探测深度为约≥8mm。术语牙周的“袋探测深度”(PPD)是指牙骨质-牙轴质接面(即顶边缘)至牙槽骨嵴的距离(以毫米测量)。PPD与CAL测量用牙周探针在各牙齿周围的不同部位(例如近中颊部位或中颊部位)进行。其提供牙周病严重性的度量。或者,PPD与CAL可获自具有一些解剖学标志的标准数字放射照相。
牙周病包括但不限于牙菌斑诱发及非牙菌斑诱发的牙龈疾病;慢性牙周炎(分类为轻度(1-2mm CAL)、中度(3-4mm CAL)、或重度(≥5mm)系统化或局部化牵涉;侵袭性牙周炎(分类为(1-2mm CAL)、中度(3-4mm CAL)、或重度(≥5mm)系统化或局部化牵涉);作为与血液学病症和遗传性病症相关的全身性疾病的表现的牙周炎;坏死性牙周疾病,包括坏死溃疡性牙龈炎和坏死性溃疡性牙周炎;牙周组织脓肿(包括牙龈、牙周和冠周脓肿);与牙髓病变相关的牙周炎;以及发育或后天性畸形和病症,例如改变或易感染牙菌斑诱发的牙龈疾病或牙周炎的局部化牙齿相关因子、牙齿周围的粘膜牙龈畸形和病状、以及缺齿脊和咬合面外伤的病状。所有这些病状可局限于一个或几个特定牙齿或更系统化(即牵涉>30%的部位)。
如本文所用的术语“晚期牙周病”是指呈现CAL≥5mm或牙周PPD≥8mm的受试者。牙龈回缩、牙齿移动、活动性以及化脓为通常与归因于牙槽骨进行性破坏的晚期牙周病相关的病征。
在一些实施方案中,牙槽骨流失因移除含有良性肿瘤的骨骼部分而产生。示例性良性骨肿瘤包括但不限于骨瘤、骨样骨瘤、骨母细胞瘤、骨软骨瘤、内生软骨瘤、软骨粘液样纤维瘤、动脉瘤样骨囊肿、单腔骨囊肿、骨纤维性发育异常以及骨骼巨细胞瘤。
施用骨硬化蛋白抑制剂增加牙槽骨的一或多个参数(例如牙槽骨高度、牙槽骨质量、牙槽骨密度、牙槽骨体积、牙槽骨矿物含量以及改善的牙齿稳定性中的一或多个)。在此方面,“治疗”牙槽骨流失包括例如牙槽骨高度、牙槽骨质量以及牙槽骨密度的任何增加以及牙槽骨修复的加速。类似地,“治疗”牙槽骨流失包括调节牙槽骨修复的程度超出(即大于)未施用骨硬化蛋白抑制剂的受试者(即对照受试者)(例如哺乳动物,如人)中所经历的牙槽骨修复的程度。牙槽骨修复通过例如与治疗之前的此类参数相比,牙槽骨高度增加、牙槽骨体积增加、牙槽骨矿物含量和密度增加、牙齿稳定性增加或受感染区域的患者使用改善来证明。牙槽骨的任何一或多个参数的增加可为测量参数完全或部分回复至例如(a)基线程度(例如在疾病发作之前的程度),(b)本领域中所用的规范化数据库或临床标准中所提供的值,或(c)对侧的功能程度(例如完全或部分地回复至例如受试者非患病牙槽骨的功能能力)。在一些情况中,增加可为超出基线程度的改善。需要时,施用一或多个剂量的骨硬化蛋白抑制剂的受试者的测量参数可与未施用骨硬化蛋白抑制剂的呈现牙槽骨流失的其它受试者(任选地年龄和性别匹配)的相同参数进行比较以进一步分析本文所述的方法的功效。
牙槽骨参数(例如牙槽骨高度、牙槽骨质量和/或牙槽骨密度)可以使用放射照相术(例如放射照相吸光光度法)、单一和/或双重能量X射线吸光光度法、定量计算机断层摄影术(QCT)、超声波扫描术、放射照相术(例如放射照相吸光光度法)以及磁共振成像来测量。在一些实施方案中,牙槽骨流失的量通过牙周袋探测深度测量来鉴别及/或定量。
在一些实施方案中,截至治疗开始后六周,施用骨硬化蛋白抑制剂(例如抗骨硬化蛋白抗体或抗体片段)的剂量和时间段有效使牙骨质-牙轴质接面与牙槽骨嵴之间的距离与治疗前距离或对照受试者(即未接受骨硬化蛋白抑制剂治疗的具有类似疾病病况的受试者)相比减小了至少10%(例如至少10%、至少20%、至少30%、至少40%、至少50%、至少60%、至少70%、至少80%、至少90%或更多)。在一些实施方案中,截至治疗开始后六周,牙骨质-牙轴质接面与牙槽骨嵴之间的距离恢复至疾病前状态。在一些实施方案中,截至治疗开始后六周,牙骨质-牙轴质接面与牙槽骨嵴之间的距离小于或等于约2mm(例如约2mm、约1.9mm、约1.8mm、约1.7mm、约1.6mm、约1.5mm、约1.4mm、约1.3mm、约1.2mm、约1.1mm或约1mm)。在一些或任何实施方案中,截至治疗开始后六周,牙骨质-牙轴质接面与牙槽骨嵴之间的距离与受试者口中的非患病区域(例如邻接或对侧牙齿)中的距离可比。
在一些实施方案中,截至治疗开始后六周,施用骨硬化蛋白抑制剂(例如抗骨硬化蛋白抗体或抗体片段)的剂量和时间段有效使牙槽骨高度与治疗前牙槽骨高度或对照受试者(即未接受骨硬化蛋白抑制剂治疗的晚期牙周病受试者)相比增加了至少10%(例如至少10%、至少20%、至少30%、至少40%、至少50%、至少60%、至少70%、至少80%、至少90%或更多)。在一些实施方案中,截至治疗开始后六周,牙槽骨高度恢复至牙槽骨高度的疾病前状态。在一些实施方案中,截至治疗开始后六周,与治疗前牙槽骨高度相比,牙槽骨高度增加了至少0.1mm(例如至少约0.1mm、约0.2mm、约0.3mm、约0.4mm、约0.5mm、约0.6mm、约0.7mm、约0.8mm、约0.9mm、约1mm、约1.5mm、约2mm、约2.5mm、约3mm、约3.5mm、约4mm、约4.5mm、约5mm、约5.5mm、约6mm、约6.5mm、约7mm、约7.5mm、约8mm、约8.5mm、约9mm、约9.5或约10mm)或更多。在一些或任何实施方案中,截至治疗开始后六周,牙槽骨高度与受试者口中的非患病区域(例如邻接或对侧牙齿)中的距离可比。
在一些实施方案中,截至治疗开始后六周,施用骨硬化蛋白抑制剂(例如抗骨硬化蛋白抗体或抗体片段)的剂量和时间段有效使牙槽骨密度与治疗前牙槽骨密度或对照受试者(即未接受骨硬化蛋白抑制剂治疗的晚期牙周病受试者)相比增加了至少10%(例如至少10%、至少20%、至少30%、至少40%、至少50%、至少60%、至少70%、至少80%、至少90%或更多)。在一些实施方案中,截至治疗开始后六周,牙槽骨密度恢复至疾病前状态牙槽骨密度(例如受试者口中的非患病牙龈区域的可比密度)。在人中,骨骼矿物密度通常使用双重x射线吸收测量法(DXA)在临床上测定。其它技术包括定量计算机断层摄影术(QCT)、超声波扫描术、单一能量x射线吸光测定法(SXA)、磁共振成像、放射照相术以及放射照相吸光测定法。除超声波扫描术以外,美国医药协会注意到BMD技术典型地包括使用x射线且基于辐射衰减取决于辐射路径中组织的厚度和组成的原理。所述技术通常包括将结果与规范化数据库作比较。
适用于评估成功的骨硬化蛋白抑制剂治疗的另一参数为牙槽骨体积分数(BVF)。如本文所用的术语“骨骼体积分数”是指每单位体积骨骼样品的矿化骨骼体积(BV/TV,%)且可例如通过微计算机断层摄影术(micro-CT)测量。在一些或任何实施方案中,截至治疗开始后六周,与治疗前牙槽骨BVF相比或与对照受试者(即不接受骨硬化蛋白抑制剂治疗的晚期牙周病受试者)相比,牙槽骨BVF增加了至少10%(例如至少10%、至少20%、至少30%、至少40%、至少50%、至少60%、至少70%、至少80%、至少90%或更多)。在一些或任何实施方案中,截至治疗开始后六周,牙槽骨BVF与受试者口中的非患病区域(例如邻接或对侧牙齿)中的牙槽骨BVF可比。
牙槽骨高度、牙槽骨质量、牙槽骨密度以及牙槽骨体积分数中的一个或多个的增加和/或牙骨质-牙轴质接面与骨骼嵴之间的距离减小(或任何其它牙槽骨参数的改进)可在最初施用骨硬化蛋白抑制剂后1周、2周、3周、4周、5周、6周、7周、8周、9周、10周或更长时间时确定。或者,牙槽骨高度、牙槽骨质量、牙槽骨体积分数以及牙槽骨密度中任一个或多个的增加(和/或牙骨质-牙轴质接面与骨骼嵴之间的距离减小)可在治疗期结束后确定(例如治疗期结束后1周、2周、3周、4周、5周、6周、7周、8周、9周、10周、11周、12周、13周、14周、15周、16周、5个月、6个月、7个月、8个月、9个月、10个月、11个月或1年)。在一个方面,所述方法减少建立牙槽骨高度、牙槽骨质量、牙槽骨密度及/或牙槽骨体积分数的所需程度和/或牙骨质-牙轴质接面与骨骼嵴之间的距离减小所需的时间量,与未接受骨硬化蛋白抑制剂的年龄和性别匹配患者相比,例如本文所述的牙槽骨高度、牙槽骨质量或牙槽骨密度和/或牙槽骨体积分数和/或牙骨质-牙轴质接面与骨骼嵴之间的距离的任何增加%,从而减少受试者恢复时间。例如,在一个实施方案中,与未接受骨硬化蛋白抑制剂的受试者相比,骨硬化蛋白抑制剂使增加牙槽骨高度、牙槽骨质量、牙槽骨密度和/或牙槽骨体积分数和/或减小牙骨质-牙轴质接面与骨骼嵴之间的距离所需的时间量减少了至少约10%(例如至少约20%、至少约25%、至少约30%、至少约35%、至少约40%、至少约45%、或至少约50%)。
指示牙槽骨增强的功能性生活质量参数包括但不限于牙齿损失风险减小;牙龈出血减少、牙周袋深度减小、牙龈组织附着程度增加、发音改善;味觉改善;食用某些食品的能力增加;张力减小;进食改善及刺激性减小。如本文所述施用一个或多个剂量的骨硬化蛋白抑制剂在测试的患者群体中以统计学上显著的方式加速与牙槽骨流失相关的功能性生活质量参数的改进。
在一些实施方案中,在一段治疗期时程内对人施用一或多个剂量的骨硬化蛋白抑制剂(如骨硬化蛋白结合剂)(例如抗骨硬化蛋白抗体或抗体片段),所述治疗期包含1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24、25、26、27、28、29、31周、8个月、9个月、10个月、11个月、1年、18个月或更长时间。“治疗期”在施用第一剂量的骨硬化蛋白抑制剂(例如抗骨硬化蛋白抗体或抗体片段)时开始且在施用最后剂量的骨硬化蛋白抑制剂之后结束。涵盖在治疗期期间施用骨硬化蛋白抑制剂任何次数。例如,在治疗期内,为受试者提供骨硬化蛋白抑制剂的1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20个剂量或施用。在一个实施方案中,治疗期包含至少6周。在一些实施方案中,治疗期持续至少28周。在其它实施方案中,治疗期持续至少1年。或者或另外,治疗期持续至多18个月。实际上,在至多18个月、少于1年、至多8个月、至多28周或至多20周的治疗或治疗期内可以进行一或多次施用包含骨硬化蛋白抑制剂的医药组合物。在一个实施方案中,治疗期为约28周且与具有牙槽骨流失的未治疗的受试者相比,牙槽骨参数,如(但不限于)牙槽骨高度、牙槽骨质量、牙槽骨体积分数以及牙槽骨密度显著改善。
施用促进、增强或加速牙槽骨修复的量的骨硬化蛋白结合剂(例如抗骨硬化蛋白抗体或抗体片段)。在任何实施方案中,骨硬化蛋白抑制剂可施用给受试者(例如人受试者),其量为每周约5毫克至约1,000毫克骨硬化蛋白抑制剂。例如,骨硬化蛋白抑制剂(例如抗骨硬化蛋白抗体或抗体片段)的量可包含至少约5mg、15mg、25mg、50mg、约60mg、约70mg、约80mg、约90mg、约100mg、约120mg、约140mg、约150mg、约170mg、约180mg、约200mg、约210mg、约240mg、约250mg、约270mg、约280mg、约300mg、约350mg、约400mg、约420mg、约450mg、约500mg、约550mg、约600mg、约650mg、约700mg、约750mg、约800mg、约850mg、约900mg、约950mg或高达约1,000mg骨硬化蛋白抑制剂。还涵盖任何和所有这些终点之间的范围,例如约50mg至约80mg、约70mg至约140mg、约70mg至约210mg、约75mg至约100mg、约100mg至约150mg、约120mg至约270mg、约140mg至约210mg、或约150mg至约200mg、或约280至约410mg。剂量以任何间隔施用,如一周多次(例如每周两次或三次)、每周一次、每两周一次、每三周一次、或每四周一次。在一些或任何实施方案中,每周两次施用约120mg至约210mg范围内的剂量的骨硬化蛋白抑制剂(例如抗骨硬化蛋白抗体或抗体片段)。在一些或任何实施方案中,每周两次施用约140mg剂量的骨硬化蛋白抑制剂(例如抗骨硬化蛋白抗体或抗体片段)。在一些或任何实施方案中,治疗期为12周,并且在治疗期的第2周、第6周以及第12周施用骨硬化蛋白,剂量任选地为约140mg。本文所述的任何剂量可以作为分次剂量施用。例如,140mg剂量的骨硬化蛋白抑制剂可在牙科医生诊视期间以两次70mg骨硬化蛋白抑制剂的注射液或7次20mg骨硬化蛋白抑制剂的注射液施用。
在一些实施方案中,向受试者(例如哺乳动物,如人)施用的骨硬化蛋白结合剂的剂量范围可为约0.1mg/kg至约100mg/kg体重或约10mg/kg至约50mg/kg体重。例如,骨硬化蛋白抑制剂(例如骨硬化蛋白结合剂)的剂量范围可为约0.1mg/kg、约0.5mg/kg、约1mg/kg、约2mg/kg、约3mg/kg、约4mg/kg、约5mg/kg、约6mg/kg、约7mg/kg、约8mg/kg、约9mg/kg、约10mg/kg、约20mg/kg、约25mg/kg、约26mg/kg、约27mg/kg、约28mg/kg、约29mg/kg、约30mg/kg、约31mg/kg、约32mg/kg、约33mg/kg、约34mg/kg、约35mg/kg、约36mg/kg、约37mg/kg、约38mg/kg、约39mg/kg、约40mg/kg、约41mg/kg、约42mg/kg、约43mg/kg、约44mg/kg、约45mg/kg、约46mg/kg、约47mg/kg、约48mg/kg、约49mg/kg、或约50mg/kg、约55mg/kg、约60mg/kg、约65mg/kg、约70mg/kg、约75mg/kg、约80mg/kg、约85mg/kg、约90mg/kg、或约95mg/kg、高达约100mg/kg体重。
另外,有利的可能是施用多次剂量的骨硬化蛋白结合剂或各剂量的施用隔开,这取决于针对特定患者而选择的治疗方案。例如,骨硬化蛋白抑制剂的剂量可每四周一次、每三周一次、每两周一次、每周一次或一周多次(例如每周两次、每周三次、每周四次或更多次)施用,这取决于疾病状态的严重性、患者的年龄和身体健康以及其类似因素。
在一些实施方案中,受试者任选地患有选自由晚期牙周病、软骨发育不全、经绝后骨质流失、口骨质流失、颌骨坏死以及与老化相关的颌骨流失组成的组的骨骼相关病症。受试者任选地正经受或已经受口或上颌面手术。
在一些实施方案中,受试者任选地患有选自由以下组成的组的继发性病状:幼年型佩吉特氏病(juvenile Paget's disease)、肢骨纹状肥大、代谢骨骼疾病、肥大细胞增多症、镰刀型细胞贫血症/疾病、器官移植相关骨质流失、肾移植相关骨质流失、全身性红斑狼疮、强直性脊椎炎、癞痫症、幼年型关节炎皮疹、地中海贫血、粘多糖症、法布里疾病(FabryDisease)、托纳综合症(Turner Syndrome)、唐氏综合症(Down Syndrome)、克兰菲特尔综合症(Klinefelter Syndrome)、麻疯病、帕瑟氏疾病(Perthe's disease)、青春特发性疹柱侧凸、婴儿的发作多系统发炎性疾病、威彻斯特综合症(Winchester Syndrome)、曼克斯疾病(Menkes Disease)、威尔逊氏疾病(Wilson's Disease)、局部缺血骨骼疾病(如雷卡佩氏病(Legg-Calve-Perthes disease)和区域性迁移骨质疏松症)、贫血状态、由类固醇引起的病状、糖皮质激素诱发的骨质流失、肝素诱发的骨质流失、骨髓病症、坏血病、营养不良、钙缺乏症、骨质疏松症、骨质减少、酒精中毒、慢性肝病、经绝后状态、慢性发炎性病状、类风湿性关节炎、发炎性肠疾病、溃疡性结肠炎、发炎性结肠炎、克罗恩氏病(Crohn's disease)、月经过少、经闭、怀孕、糖尿病、甲状腺机能亢进、甲状腺病症、甲状旁腺病症、库欣氏病(Cushing's disease)、肢端肥大症、性腺低能症、固定化或废弃、反射性交感神经营养不良综合症、区域性骨质疏松症、骨软化、与关节移位相关的骨质流失、HIV相关骨质流失、与生长激素损失相关骨质流失、与囊肿性纤维化相关骨质流失、化学疗法相关的骨质流失、肿瘤诱发的骨质流失、癌症相关的骨质流失、激素易消融骨质流失、多发性骨髓瘤、药物诱发的骨质流失、神经性厌食、疾病相关面骨损失、疾病相关颅骨损失、疾病相关颌骨质流失、疾病相关颅骨骨质流失、与老化相关骨质流失、与老化相关面骨损失、与老化相关颅骨损失、锁骨颅骨发育不全、软骨发育不良、纤维性结构不良、高雪氏病(Gaucher's Disease)、血磷酸盐过少佝偻病、马氏综合症(Marfan's syndrome)、多发性遗传性外生骨疣、多发性神经纤维瘤、成骨不全、骨硬化病、脆弱性骨硬化、巩膜病变、假关节、化脓性骨髓炎、牙周病、抗癞痫药物诱发的骨质流失、原发性和继发性甲状旁腺机能亢进、家族性甲状旁腺机能亢进综合症、失重诱发的骨质流失、男性骨质疏松症、骨关节炎、肾病性骨营养不良、骨骼渗透性病症、与老化相关颅骨骨质流失、以及与航天飞行相关的骨质流失。
在一些实施方案中,受试者任选地患有(或已患有)癌症。术语“癌症”是指与不受控制的细胞增殖、无限制的细胞生长、以及降低的细胞死亡/细胞凋亡相关的增殖病症。癌症包括但不限于乳癌、前列腺癌、肺癌、肾癌、甲状腺癌、黑色素瘤、滤泡性淋巴瘤、p53突变癌、以及激素依赖性肿瘤,包括但不限于结肠癌、心脏肿瘤、胰腺癌、成视网膜细胞瘤、成胶质细胞瘤、肠癌、睾丸癌、胃癌、神经母细胞瘤、粘液瘤、肌瘤、淋巴瘤、内皮瘤、骨母细胞瘤、破骨细胞瘤、骨肉瘤、软骨肉瘤、腺瘤、卡波西氏肉瘤(Kaposi's sarcoma)、卵巢癌、白血病(包括急性白血病(例如急性淋巴球性白血病、急性髓细胞性白血病,包括成髓细胞、前髓细胞、粒单核细胞、单核细胞以及红白血病)和慢性白血病(例如慢性髓细胞(粒细胞)白血病以及慢性淋巴细胞白血病)、骨髓发育不良综合症真性红细胞增多症、淋巴瘤(例如霍奇金氏病和非霍奇金氏病)、多发性骨髓瘤、万达斯曲姆氏巨球蛋白血症(Waldenstrom'smacroglobulinemia)、重链疾病,以及实体肿瘤包括但不限于肉瘤和癌瘤,如纤维肉瘤、粘液肉瘤、脂肪肉瘤、骨肉瘤、脊索瘤、血管肉瘤、内皮肉瘤、淋巴管肉瘤、淋巴管内皮肉瘤、滑膜瘤、间皮瘤、尤因氏肿瘤(Ewing's tumor)、平滑肌肉瘤、横纹肌肉瘤、鳞状细胞癌瘤、基底细胞癌、腺癌、汗腺癌、皮脂腺癌、乳头状癌瘤、乳头状腺癌、囊腺癌、髓性癌、支气管癌、肾细胞癌、肝瘤、胆管癌、绒膜癌、精原细胞瘤、胚胎癌、威姆氏肿瘤(Wilm's tumor)、子宫颈癌、小细胞肺癌、膀胱癌、上皮癌、神经胶质瘤、星形细胞瘤、成神经管细胞瘤、颅咽管瘤、室管膜瘤、松果体瘤、成血管细胞瘤、听神经瘤、少枝胶质瘤以及脑膜瘤(menangioma)。术语“转移”和“癌转移”本文互换使用来指癌细胞扩散至其它组织的能力。例如,“转移至骨骼”是指某些类型的癌症转移至骨骼的能力,所述类型的癌症包括但不限于乳腺、前列腺、肺、肾、甲状腺以及黑色素瘤。
本文所述的方法还适用于其它形式的牙周病,包括与以下全身性病症相关的牙周病:如心血管疾病、中风、肺病、发炎性疾病以及全身性红斑狼疮;与以下代谢障碍相关的牙周病:如糖尿病;以及与与例如绝经期相关的激素变化相关的牙周病。使用某些药物(如抗惊厥药、钙离子通道封闭剂以及环孢素)也可升高牙龈增生或牙周病风险,包括由例如HIV引起的免疫系统病症的某些血液学病症也如此。尤其涵盖用本文所述的骨硬化蛋白抑制剂治疗患有上述病症或有风险患上述病症的受试者。
在一些实施方案中,受试者任选地患有溶骨病症。如本文所用的术语“溶骨病症”是指由破骨细胞活性增加引起的任何病状,破骨细胞为造成骨吸收的细胞。术语“骨质溶解”和“溶骨骨质流失”互换使用来指破骨细胞介导的骨吸收或与溶骨病症相关的骨质流失。溶骨病症发生在具有发展溶骨病症倾向的受试者中,或其发生在患有因刺激破骨细胞活性而导致或促成溶骨病症的疾病的受试者中。在一些实施方案中,溶骨病症为溶骨骨质流失。在其它实施方案中,溶骨病症为癌症转移诱发的溶骨骨质流失。在其它实施方案中,溶骨病症为代谢骨骼疾病,包括但不限于内分泌病(例如皮质醇过多症、性腺低能症、原发性或继发性甲状旁腺功能亢进、以及甲状腺机能亢进);营养缺乏,包括但不限于佝偻病、骨软化、坏血病以及营养不良;骨质疏松症;药物使用,包括糖皮质激素(糖皮质激素诱发的骨质疏松症)、肝素以及酒精;慢性疾病,包括吸收不良综合症;慢性肾衰竭,包括肾病性骨营养不良;慢性肝病,包括肝骨营养不良;遗传性疾病,包括成骨不全和高胱氨酸尿症;以及与关节炎、类风湿性关节炎、牛皮癣关节炎、纤维性结构不良、牙周病以及佩吉特氏病相关的骨骼发炎。
术语“转移诱发的溶骨骨质流失”和“癌症转移诱发的溶骨骨质流失”本文互换使用来指由癌细胞转移至骨骼产生的骨质溶解或溶骨骨质流失。术语“癌症转移诱发的破骨细胞活化”本文用来指已转移至骨骼的癌细胞诱发破骨细胞活化的能力。
本文所述的方法包括施用一定量的“骨硬化蛋白抑制剂”。如本文所用的术语“骨硬化蛋白抑制剂”意指抑制骨上的骨硬化蛋白的生物活性的任何分子,如由以下各项的变化所测量:骨骼矿化、骨骼密度、骨骼高度、对骨母细胞和/或破骨细胞的作用、骨形成标记物、骨吸收标记物、骨母细胞活性标记物和/或破骨细胞活性标记物。此类抑制剂可通过结合骨硬化蛋白或其受体或结合搭配物来起作用。这个类别中的抑制剂包括“骨硬化蛋白结合剂”,例如像抗体或基于肽的分子。“骨硬化蛋白抑制剂”还指结合骨硬化蛋白并且抑制其活性的任选地分子量小于约1000道尔顿的小有机化学化合物。抑制剂或者可通过抑制骨硬化蛋白的表达起作用。这一类别中的抑制剂包括结合骨硬化蛋白DNA或mRNA且抑制骨硬化蛋白表达的多核苷酸或寡核苷酸,包括但不限于反义寡核苷酸、抑制性RNA、DNA酶(脱氧核糖酶)、核糖酶、适体或抑制骨硬化蛋白表达的其医药学上可接受的盐。
“骨硬化蛋白结合剂”结合骨硬化蛋白或其一部分以便封闭或减弱人骨硬化蛋白与一种或多种配体的结合。骨硬化蛋白,SOST基因的产物,不存在于硬化性骨化病中,硬化性骨化病为一种特征在于骨骼过度生长和强密度骨的骨骼疾病(Brunkow等人,Am.J.Hum.Genet.,68:577-589(2001);Balemans等人,Hum.Mol.Genet.,10:537-543(2001))。人骨硬化蛋白的氨基酸序列由Brunkow等人报告且以SEQ ID NO:1公开于美国专利公布号20070110747(所述专利公布的骨硬化蛋白结合剂的描述和序列表全部并入)。重组人骨硬化蛋白/SOST可购自R&D Systems(Minneapolis,Minn.,USA;2006目录号1406-ST-025)。另外,重组小鼠骨硬化蛋白/SOST可购自R&D Systems(Minneapolis,Minn.,USA;2006目录号1589-ST-025)。研究级骨硬化蛋白结合单克隆抗体可购自R&D Systems(Minneapolis,Minn.,USA;小鼠单克隆:2006目录号MAB1406;大鼠单克隆:2006目录号MAB1589)。美国专利号6,395,511和6,803,453以及美国专利公布号20040009535和20050106683总体上涉及抗骨硬化蛋白抗体。适合用于本发明的上下文的骨硬化蛋白结合剂的实例还描述于美国专利公布号20070110747和20070072797中,所述公布特此以引用的方式并入。关于产生骨硬化蛋白结合剂的材料和方法的另外的信息可见于美国专利公布号20040158045(特此以引用的方式并入)。
本发明的骨硬化蛋白结合剂优选为抗体。术语“抗体”是指完整抗体或其结合片段。抗体可包含完全抗体(免疫球蛋白)分子(包括具有全长重链和/或轻链的多克隆、单克隆、嵌合、人源化和/或人形式),或包含其抗原结合片段。抗体片段包括F(ab')2、Fab、Fab'、Fv、Fc以及Fd片段,并且可并入单结构域抗体(例如奈米抗体)、单链抗体、最大抗体、微型抗体、内抗体、双抗体、三抗体、四抗体、v-NAR以及bis-scFv(参见例如Hollinger和Hudson,Nature Biotechnology,23(9):1126-1136(2005))。抗体多肽,包括纤连蛋白多肽单抗体,也公开于美国专利号6,703,199中。其它抗体多肽公开于美国专利公布号20050238646中。美国专利号6,395,511和6,803,453以及美国专利公布号20040009535和20050106683(其抗骨硬化蛋白抗体的公开内容以引用的方式全部并入)总体上涉及抗骨硬化蛋白抗体。人骨硬化蛋白的氨基酸序列阐述于序列表的SEQ ID NO:1中且以美国专利公布号20070110747的SEQ ID NO:1提供(所述专利公布的骨硬化蛋白和骨硬化蛋白结合剂的描述和序列表全部并入)。关于产生抗骨硬化蛋白抗体的材料和方法的另外信息可见于美国专利公布号20040158045(特此以引用的方式全部并入)。
抗体片段可为合成或基因工程化蛋白质。例如,抗体片段包括由轻链可变区组成的分离的片段、由重链和轻链可变区组成的“Fv”片段,以及轻链与重链可变区经由肽连接子连接的重组单链多肽分子(scFv蛋白质)。
抗体片段的另一形式为包含抗体的一个或多个互补决定区(CDR)的肽。CDR(还称为“最小识别单位”或“高变区”)通过例如构筑编码所关注的CDR的多核苷酸获得。此类多核苷酸例如通过利用聚合酶链反应使用抗体产生细胞的mRNA作为模板合成可变区来制备(参见例如Larrick等人,Methods:A Companion to Methods in Enzymology,2:106(1991);Courtenay-Luck,“Genetic Manipulation of Monoclonal Antibodies”,见MonoclonalAntibodies Production,Engineering and Clinical Application,Ritter等人(编),第166页,Cambridge University Press(1995);以及Ward等人,“Genetic Manipulation andExpression of Antibodies”,见Monoclonal Antibodies:Principles andApplications,Birch等人(编),第137页,Wiley-Liss,Inc.(1995))。
抗骨硬化蛋白抗体可结合SEQ ID NO:1的骨硬化蛋白或其天然存在的变异体,亲和力(Kd)为小于或等于1x10-7M、小于或等于1x10-8M、小于或等于1x10-9M、小于或等于1x10-10M、小于或等于1x10-11M、或小于或等于1x10-12M。亲和力利用多种技术测定,所述技术的一个实例为亲和力ELISA分析。在不同的实施方案中,亲和力通过BIAcore测定来测定。在不同的实施方案中,亲和力通过动力学方法测定。在不同的实施方案中,亲和力通过平衡/溶液法测定。美国专利公布号20070110747含有适于测定抗体对骨硬化蛋白的亲和力(Kd)的亲和力测定的其它描述。
在一些或任何实施方案中,抗骨硬化蛋白抗体或抗体片段结合包含SEQ ID NO:1中所述的氨基酸序列的骨硬化蛋白多肽,并结合S EQ ID NO:6(CGPARLLPNAIGRGKWWRPSGPDFRC;对应于S EQ ID NO:1的氨基酸86-111)的序列。或者或另外,抗骨硬化蛋白抗体结合包含SEQ ID NO:1的氨基酸57-146的骨硬化蛋白多肽。或者或另外,抗骨硬化蛋白抗体结合包含SEQ ID NO:1的氨基酸89-103和/或SEQ ID NO:1的氨基酸137-151的骨硬化蛋白多肽。或者或另外,抗骨硬化蛋白抗体结合包含SEQ ID NO:1中所述的氨基酸序列的骨硬化蛋白多肽并且结合SEQ ID NO:1内的以下中至少一者的序列:SEQID NO:2(DVSEYSCRELHFTR;对应于SEQ ID NO:1的氨基酸51-64)、SEQ ID NO:3(SAKPVTELVCSGQCGPAR;对应于SEQ ID NO:1的氨基酸73-90)、SEQ ID NO:4(WWRPSGPDFRCIPDRYR;对应于SEQ ID NO:1的氨基酸101-117);SEQ ID NO:5(LVASCKCKRLTR;对应于SEQ ID NO:1的氨基酸 138-149)、SEQ ID NO:70(SAKPVTELVCSGQC;对应于SEQ ID NO:1的氨基酸73-86)、SEQID NO:71(LVASCKC;对应于SEQ ID NO:1的氨基酸138-144)、SEQ ID NO:72(C1RE LHFTR;对应于SEQ ID NO:1的氨基酸57-64)、或SEQ ID NO:73(CIPDRYR;对应于SEQ ID NO:1的氨基酸111-117)。例如,在一个方面,抗骨硬化蛋白抗体结合包含SEQ ID NO:2-5(和/或S EQ IDNO:70-73)(任选地呈其天然三维构形)的SEQ ID NO:1的骨硬化蛋白的亚区。任选地,抗骨硬化蛋白抗体结合由SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID N O:6、SEQ ID NO:70、SEQ ID NO:71、SEQ ID NO:72或SEQ ID NO:73中的一个或多个组成的肽(例如由SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4以及SEQ ID NO:5组成的肽或由SE Q IDNO:70、SEQ ID NO:71、SEQ ID NO:72以及SEQ ID N O:73组成的肽)。
在一些或任何实施方案中,抗骨硬化蛋白抗体结合具有SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4以及SEQ ID NO:5的氨基酸序列的骨硬化蛋白多肽,其中SEQ ID NO:2与4在参考SEQ ID NO:1的氨基酸位置57和111处通过二硫键连接,并且SEQ ID NO:3与5通过以下中的至少一者连接:(a)在参考SEQ ID NO:1的氨基酸位置82和142处的二硫键,以及(b)在参考SEQ ID NO:1的氨基酸位置86和144处的二硫键;所述多肽可保留SEQ ID NO:1的人骨硬化蛋白的相应多肽区的三级结构。或者或另外,骨硬化蛋白结合剂(例如抗骨硬化蛋白抗体)结合具有SEQ ID NO:70、SEQ ID NO:71、SEQ ID NO:72以及SEQ ID NO:73的氨基酸序列的多肽,其中SEQ ID NO:72与73在参考SEQ ID NO:1的氨基酸位置57和111处通过二硫键连接,并且SEQ ID NO:70与71通过以下中的至少一者连接:(a)在参考SEQ ID NO:1的氨基酸位置82和142处的二硫键,以及(b)在参考SEQ ID NO:1的氨基酸位置86和144处的二硫键。
任选地,抗骨硬化蛋白抗体结合基本上由SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4以及SEQ ID NO:5的氨基酸序列组成的肽,其中SEQ ID NO:2与4在参考SEQ ID NO:1的氨基酸位置57和111处通过二硫键连接,并且SEQ ID NO:3与5通过以下中的至少一者连接:(a)在参考SEQ ID NO:1的氨基酸位置82和142处的二硫键,以及(b)在参考SEQ ID NO:1的氨基酸位置86和144处的二硫键。
任选地,抗骨硬化蛋白抗体结合基本上由SEQ ID NO:1的多截断人骨硬化蛋白组成的多肽,其中(a)所述多肽无SEQ ID NO:1的氨基酸1-50、65-72、91-100、118-137以及150-190,或(b)所述多肽无SEQ ID NO:1的氨基酸1-56、65-72、87-110、118-137以及145-190。
在一些或任何实施方案中,抗骨硬化蛋白抗体结合具有SEQ ID NO:70、SEQ IDNO:71、SEQ ID NO:72以及SEQ ID NO:73的氨基酸序列的多肽,其中SEQ ID NO:72与73在参考SEQ ID NO:1的氨基酸位置57和111处通过二硫键连接,并且SEQ ID NO:70与71通过以下中的至少一者连接:(a)在参考SEQ ID NO:1的氨基酸位置82和142处的二硫键,以及(b)在参考SEQ ID NO:1的氨基酸位置86和144处的二硫键。
在一些或任何实施方案中,多肽保多留SEQ ID NO:l的人骨硬化蛋白的相应肽区的三级结构。
在一些或任何实施方案中,抗骨硬化蛋白抗体结合:
(i)人骨硬化蛋白的包含SEQ ID NO:1的51-64、73-90、101-117以及138-149的一部分,其中所述部分具有以下至少一者、至少两者或所有三者:
(a)氨基酸57与111之间的二硫键;
(b)氨基酸82与142之间的二硫键;以及
(c)氨基酸86与144之间的二硫键;或
(ii)人骨硬化蛋白的包含SEQ ID NO:1的57-64、73-86、111-117以及138-144的一部分,其中所述部分具有以下至少一者、至少两者或所有三者:
(a)氨基酸57与111之间的二硫键;
(b)氨基酸82与142之间的二硫键;以及
(c)氨基酸86与144之间的二硫键。
在一些或任何实施方案中,抗骨硬化蛋白抗体还结合SEQ ID NO:6的表位。
本文所述的方法中使用的抗骨硬化蛋白抗体优选在美国专利公布号2007/0110747中所述的基于细胞的测定中和/或在美国专利公布号20070110747中所述的体内分析中调节骨硬化蛋白功能,和/或结合美国专利公布号2007/0110747中所述的一个或多个表位和/或交叉封闭美国专利公布号2007/0110747中所述的抗体中的一个的结合和/或通过美国专利公布号2007/0110747中所述的抗体中的一个交叉封闭结合骨硬化蛋白(其表征抗骨硬化蛋白抗体的测定的描述以引用的方式全部并入)。
在不同的方面,当与每孔的骨硬化蛋白摩尔数相比,每孔存在少于6倍过量的摩尔数的骨硬化蛋白结合位点时,在基于MC3T3细胞的矿化测定中,所述抗骨硬化蛋白抗体能够中和人骨硬化蛋白。使用培养物中的骨母细胞谱系细胞(原代细胞或细胞系)矿化作为骨形成的体外模型。示例性基于细胞的矿化测定描述于美国专利公布号20070110747的例如实施例8(特此以引用的方式并入)中。MC3T3-E1细胞(Sudo等人,J.Cell Biol.,96:191-198(1983))和原始细胞系的亚克隆在分化剂存在下生长之后可形成培养物中的矿物。此类亚克隆包括MC3T3-E1-BF(Smith等人,J.Biol.Chem.,275:19992-20001(2000))。对于MC3T3-E1-BF亚克隆以及原始MC3T3-E1细胞,骨硬化蛋白可抑制一个或多个导致且包括矿物沉积的一系列事件(即骨硬化蛋白抑制矿化)。能够中和骨硬化蛋白抑制活性的抗骨硬化蛋白抗体允许培养物在骨硬化蛋白存在下矿化,以致例如磷酸钙(作为钙加以测量)沉积与仅骨硬化蛋白(即无抗体)治疗组中所测量的钙量相比统计上显着增加。
当以测定特定抗骨硬化蛋白抗体(或其它骨硬化蛋白抑制剂)是否可以中和骨硬化蛋白为目标进行测定时,测定中所用的骨硬化蛋白的量理想地为与无骨硬化蛋白组中所测量的钙量相比,在仅骨硬化蛋白组中引起统计上显著的至少70%的磷酸钙(作为钙加以测量)沉积减少的骨硬化蛋白的最低量。抗骨硬化蛋白中和抗体定义为与仅骨硬化蛋白(即无抗体)治疗组中测量的钙量相比引起磷酸钙(作为钙加以测量)沉积统计上显著增加的抗体。为测定抗骨硬化蛋白抗体是中和性的还是非中和性的,用于测定中的抗骨硬化蛋白抗体的量需要使得,与每孔骨硬化蛋白摩尔数相比每孔骨硬化蛋白结合位点的摩尔数为过量的。取决于抗体效能而定,可能需要的倍数过量可为24、18、12、6、3或1.5,并且所属领域的技术人员熟悉测试超过一个浓度的结合剂(抗体)的常规实践。例如,当与每孔的骨硬化蛋白摩尔数相比,每孔存在少于六倍过量的摩尔数的骨硬化蛋白结合位点时,极有效的抗骨硬化蛋白中和抗体将中和骨硬化蛋白。不太有效的抗骨硬化蛋白中和抗体将仅在12、18或24倍过量下中和骨硬化蛋白。
在基于细胞的分析如骨骼特异性碱性磷酸酶测定(例如国际专利公布号WO 2008/115732和美国专利7,744,874(基于细胞的测定和抗骨硬化蛋白抗体的描述以引用的方式全文并入本文中)中描述的骨骼特异性碱性磷酸酶测定)中,抗骨硬化蛋白抗体中和人骨硬化蛋白的IC50任选地为100nM或更小,或75nM或更小,或50nM或更小,或25nM或更小。骨骼特异性碱性磷酸酶测定基于骨硬化蛋白降低多潜能鼠类细胞系C2C12中BMP-4和Wnt3a刺激的碱性磷酸酶含量的能力。根据WO 2008/115732,中和抗骨硬化蛋白抗体在此测定中介导碱性磷酸酶活性的剂量依赖性增加。基于细胞的测定的示例性方案提供于实施例1中。
或者或另外,在HEK293细胞系中在基于细胞的Wnt信号传导测定如国际专利公布号WO 2009/047356中描述的STF报告基因的牵涉Wnt1介导诱发的Wnt测定(基于细胞的测定和抗骨硬化蛋白抗体的论述以引用的方式并入)中,抗骨硬化蛋白抗体中和人骨硬化蛋白的IC50为100nM或更小(例如75nM或更小,或50nM或更小)。或者或另外,在MC3T3细胞中的BMP2诱发的矿化测定如描述于例如国际专利公布号WO 2009/047356中的矿化测定中,抗骨硬化蛋白抗体中和人骨硬化蛋白的IC50为500nM或更小(例如250nM或更小、150nM或更小、100nM或更小、或50nM或更小)。示例性方案提供于实例1中。
适合用于本发明的上下文的抗骨硬化蛋白抗体的实例描述于美国专利公布号2007/0110747和2007/0072797中,所述公布特此以引用的方式并入。在本发明的一个实施方案中,抗骨硬化蛋白抗体交叉封闭至少一种以下抗体与骨硬化蛋白结合:Ab-A、Ab-B、Ab-C、Ab-D、Ab-1、Ab-2、Ab-3、Ab-4、Ab-5、Ab-6、Ab-7、Ab-8、Ab-9、Ab-10、Ab-11、Ab-12、Ab-13、Ab-14、Ab-15、Ab-16、Ab-17、Ab-18、Ab-19、Ab-20、Ab-21、Ab-22、Ab-23以及Ab-24(全部描述于美国专利公布号20070110747中)。或者或另外,抗骨硬化蛋白抗体被至少一种以下抗体交叉封闭与骨硬化蛋白的结合:Ab-A、Ab-B、Ab-C、Ab-D、Ab-1、Ab-2、Ab-3、Ab-4、Ab-5、Ab-6、Ab-7、Ab-8、Ab-9、Ab-10、Ab-11、Ab-12、Ab-13、Ab-14、Ab-15、Ab-16、Ab-17、Ab-18、Ab-19、Ab-20、Ab-21、Ab-22、Ab-23以及Ab-24(全部描述于美国专利公布号20070110747中)。术语“交叉封闭(cross-block、cross-blocked以及cross-blocking)”本文互换使用以意指抗体干扰其它抗体与骨硬化蛋白的结合的能力。抗体能够干扰另一者与骨硬化蛋白结合的程度且因此是否可认为其交叉封闭可使用竞争结合测定来确定。在本发明的一些方面,交叉封闭抗体或其片段使参考抗体的硬化蛋白结合减少了约40%至约100%、如约60%至约100%、尤其70%至100%、且更尤其80%至100%。检测交叉封闭的尤其适合的定量测定使用利用表面等离子体共振技术测量相互作用程度的Biacore机器。另一适合的定量交叉封闭测定使用基于ELISA的方法测量抗体之间结合骨硬化蛋白的竞争。
在一些或任何实施方案中,抗骨硬化蛋白抗体交叉封闭包含全长重链和轻链的免疫球蛋白与SEQ ID NO:1的骨硬化蛋白的结合和/或被包含全长重链和轻链的免疫球蛋白交叉封闭与SEQ ID NO:1的骨硬化蛋白的结合,其中所述包含全长重链和轻链的免疫球蛋白包含本文公开的CDR序列,如以下三组CDR序列中的一者:a)SEQ ID NO:284的CDR-L1、SEQID NO:285的CDR-L2、SEQ ID NO:286的CDR-L3、SEQ ID NO:296的CDR-H1、SEQ ID NO:297的CDR-H2、以及SEQ ID NO:298的CDR-H3;b)SEQ ID NO:48的CDR-L1、SEQ ID NO:49的CDR-L2、SEQ ID NO:50的CDR-L3、SEQ ID NO:45的CDR-H1、SEQ ID NO:46的CDR-H2、以及SEQ ID NO:47的CDR-H3;或c)SEQ ID NO:42的CDR-L1、SEQ ID NO:43的CDR-L2、SEQ ID NO:44的CDR-L3、SEQ ID NO:39的CDR-H1、SEQ ID NO:40的CDR-H2、以及SEQ ID NO:41的CDR-H3。或者或另外,抗骨硬化蛋白抗体交叉封闭包含全长重链和轻链的免疫球蛋白与SEQ ID NO:1的骨硬化蛋白的结合和/或被包含全长重链和轻链的免疫球蛋白交叉封闭与SEQ ID NO:1的骨硬化蛋白的结合,其中所述包含全长重链和轻链的免疫球蛋白包含以下CDR:SEQ ID NO:245的CDR-H1、SEQ ID NO:246的CDR-H2、SEQ ID NO:247的CDR-H3、SEQ ID NO:78的CDR-L1、SEQ ID NO:79的CDR-L2以及SEQ ID NO:80的CDR-L3。
或者或另外,抗骨硬化蛋白抗体交叉封闭包含全长重链和轻链的免疫球蛋白与SEQ ID NO:1的骨硬化蛋白的结合和/或被包含全长重链和轻链的免疫球蛋白交叉阻断与SEQ ID NO:1的骨硬化蛋白的结合,其中所述包含全长重链和轻链的免疫球蛋白包含以下CDR:SEQ ID NO:269的CDR-H1、SEQ ID NO:270的CDR-H2、SEQ ID NO:271的CDR-H3、SEQ IDNO:239的CDR-L1、SEQ ID NO:240的CDR-L2以及SEQ ID NO:241的CDR-L3。
适合的抗骨硬化蛋白抗体和其片段的实例包括具有本文特定公开且美国专利公布号20070110747中所公开的CDR-H1、CDR-H2、CDR-H3、CDR-L1、CDR-L2以及CDR-L3中的一或多个的抗体和抗体片段。CDR-H1、CDR-H2、CDR-H3、CDR-L1、CDR-L2以及CDR-L3的区中的至少一者可具有至少一个氨基酸取代,其限制条件为抗体保留未经取代的CDR的结合特异性。示例性抗骨硬化蛋白抗体包括但不限于美国专利公布号20070110747的Ab-A、Ab-B、Ab-C、Ab-D、Ab-1、Ab-2、Ab-3、Ab-4、Ab-5、Ab-6、Ab-7、Ab-8、Ab-9、Ab-10、Ab-11、Ab-12、Ab-13、Ab-14、Ab-15、Ab-16、Ab-17、Ab-18、Ab-19、Ab-20、Ab-21、Ab-22、Ab-23以及Ab-24。
另外,抗骨硬化蛋白抗体可包含至少一个与选自以下的CDR具有至少75%一致性(例如100%一致性)的CDR序列:SEQ ID NO:39、40、41、42、43、44、45、46、47、48、49、50、51、52、53、54、55、56、57、58、59、60、61、62、78、79、80、81、99、100、101、102、103、104、105、106、107、108、109、110、111、112、113、114、115、116、237、238、239、240、241、242、243、244、245、246、247、248、249、250、251、252、253、254、255、256、257、258、259、260、261、262、263、264、265、266、267、268、269、270、271、272、273、274、275、276、277、278、279、280、281、282、283、284、285、286、287、288、289、290、291、292、293、294、295、296、297、298、351、352、353、358、359以及360,其提供于序列表中且公开于美国专利公布号20070110747中。抗骨硬化蛋白抗体优选包含至少一个与选自以下的CDR具有至少75%一致性的CDR序列:SEQ ID NO:245、246、247、78、79、80、269、270、271、239、240以及241,其全部提供于序列表中且描述于美国专利公布号20070110747中。如美国专利公布号20070110747所述,抗骨硬化蛋白抗体可包含:a)SEQ ID NO:54、55以及56的CDR序列和SEQ ID NO:51、52以及53的CDR序列;b)SEQ IDNO:60、61以及62的CDR序列和SEQ ID NO:57、58以及59的CDR序列;c)SEQ ID NO:48、49以及50的CDR序列和SEQ ID NO:45、46以及47的CDR序列;d)SEQ ID NO:42、43以及44的CDR序列和SEQ ID NO:39、40以及41的CDR序列;e)SEQ ID NO:275、276以及277的CDR序列和SEQ IDNO:287、288以及289的CDR序列;f)SEQ ID NO:278、279以及280的CDR序列和SEQ ID NO:290、291以及292的CDR序列;g)SEQ ID NO:78、79以及80的CDR序列和SEQ ID NO:245、246以及247的CDR序列;h)SEQ ID NO:81、99以及100的CDR序列和SEQ ID NO:248、249以及250的CDR序列;i)SEQ ID NO:101、102以及103的CDR序列和SEQ ID NO:251、252以及253的CDR序列;j)SEQ ID NO:104、105以及106的CDR序列和SEQ ID NO:254、255以及256的CDR序列;k)SEQ ID NO:107、108以及109的CDR序列和SEQ ID NO:257、258以及259的CDR序列;l)SEQ IDNO:110、111以及112的CDR序列和SEQ ID NO:260、261以及262的CDR序列;m)SEQ ID NO:281、282以及283的CDR序列和SEQ ID NO:293、294以及295的CDR序列;n)SEQ ID NO:113、114以及115的CDR序列和SEQ ID NO:263、264以及265的CDR序列;o)SEQ ID NO:284、285以及286的CDR序列和SEQ ID NO:296、297以及298的CDR序列;p)SEQ ID NO:116、237以及238的CDR序列和SEQ ID NO:266、267以及268的CDR序列;q)SEQ ID NO:239、240以及241的CDR序列和SEQ ID NO:269、270以及271的CDR序列;)SEQ ID NO:242、243以及244的CDR序列以及SEQ ID NO:272、273以及274的CDR序列;或s)SEQ ID NO:351、352以及353的CDR序列和SEQ ID NO:358、359以及360的CDR序列。
抗骨硬化蛋白抗体可包含至少一个与选自以下的CDR具有至少75%一致性(例如100%一致性)的CDR序列:CDR-H1、CDR-H2、CDR-H3、CDR-L1、CDR-L2以及CDR-L3,其中CDR-H1具有SEQ ID NO:245中给出的序列,CDR-H2具有SEQ ID NO:246中给出的序列,CDR-H3具有SEQ ID NO:247中给出的序列,CDR-L1具有SEQ ID NO:78中给出的序列,CDR-L2具有SEQ IDNO:79中给出的序列,并且CDR-L3具有SEQ ID NO:80中给出的序列,全部提供于序列表中并且描述于美国专利公布号20070110747中。在不同的方面,抗骨硬化蛋白抗体包含两个CDR或六个CDR。任选地,抗骨硬化蛋白抗体包含含有SEQ ID NO:378的重链(例如两个重链)的全部或一部分以及含有SEQ ID NO 376的轻链(例如两个轻链)的全部或一部分。
抗骨硬化蛋白抗体可包含至少一个与选自以下的CDR具有至少75%一致性(例如100%一致性)的CDR序列:CDR-H1、CDR-H2、CDR-H3、CDR-L1、CDR-L2以及CDR-L3,其中CDR-H1具有SEQ ID NO:269中给出的序列,CDR-H2具有SEQ ID NO:270中给出的序列,CDR-H3具有SEQ IDNO:271中给出的序列,CDR-L1具有SEQ ID NO:239中给出的序列,CDR-L2具有SEQ IDNO:240中给出的序列,并且CDR-L3具有SEQ ID NO 241中给出的序列,全部提供于序列表中并且描述于美国专利公布号20070110747中。在不同的方面,抗骨硬化蛋白抗体包含至少两个CDR或六个CDR。任选地,抗骨硬化蛋白抗体包含含有SEQ ID NO:366的重链(例如两个重链)的全部或一部分以及含有SEQ ID NO 364的轻链(例如两个轻链)的全部或一部分.
或者,抗骨硬化蛋白抗体可具有重链,所述重链包含CDR的H1、H2以及H3并且包含具有SEQ ID NO:137、145或392中所提供的序列或其变体的多肽,其中CDR分别与SEQ IDNO:245、246以及247具有至少75%一致性(例如100%一致性);以及轻链,所述轻链包含CDR的L1、L2及L3并且包含具有SEQ ID NO:133或141中所提供的序列或其变体的多肽,其中CDR分别与SEQ ID NO:78、79以及80具有至少75%一致性(例如100%一致性)(如美国专利公布号20070110747中所述)。
抗骨硬化蛋白抗体可具有重链,所述重链包含CDR的H1、H2以及H3并且包含具有SEQ ID NO:335、331、345或396中所提供的序列或任何上述者的变体的多肽,其中CDR分别与SEQ ID NO:269、270以及271具有至少75%一致性(例如100%一致性);以及轻链,所述轻链包含CDR的L1、L2以及L3并且包含具有SEQ ID NO:334或341中所提供的序列或任何上述者的变体的多肽,其中CDR分别与SEQ ID NO:239、240以及241具有至少75%一致性(例如100%一致性)(如美国专利公布号20070110747中所述)。涵盖重链与轻链序列的所有组合(例如包含SEQ ID NO:335的重链和包含SEQ ID NO:334的轻链;包含SEQ ID NO:331的重链和包含SEQ ID NO:334或341的轻链;以及包含SEQ ID NO:345或396的重链和包含SEQ IDNO:341的轻链)。
或者,抗骨硬化蛋白抗体具有包含具有SEQ ID NO:137中提供的序列的多肽的重链、以及包含具有SEQ ID NO:133中提供的序列的多肽的轻链;包含具有SEQ ID NO:145或392中提供的序列的多肽的重链、以及包含具有SEQ ID NO:141中提供的序列的多肽的轻链;包含具有SEQ ID NO:335中提供的序列的多肽的重链、以及包含具有SEQ ID NO:334中提供的序列的多肽的轻链;包含具有SEQ ID NO:331中提供的序列的多肽的重链、以及包含具有SEQ ID NO:341中提供的序列的多肽的轻链;包含具有SEQ ID NO:345或396中提供的序列的多肽的重链、以及包含具有SEQ ID NO:341中提供的序列的多肽的轻链(如美国专利公布号20070110747中所述)。
抗骨硬化蛋白抗体的实例还包括但不限于国际专利公布号WO2008/092894、WO2008/115732、WO 2009/056634、WO 2009/047356、WO 2010/100200、WO 2010/100179、WO2010/115932以及WO2010/130830中所公开的抗骨硬化蛋白抗体(各以引用的方式全部并入本文中),如包含国际专利公布号WO 2008/115732的SEQ ID NO:20-25(本文中的SEQ IDNO:416-421)的CDR的抗骨硬化蛋白抗体、包含国际专利公布号WO 2008/115732的SEQ IDNO:26-31(本文中的SEQ ID NO:422-427)的CDR的抗骨硬化蛋白抗体、包含国际专利公布号WO 2008/115732的SEQ ID NO:32-37(本文中的SEQ ID NO:428-433)的CDR的抗骨硬化蛋白抗体、包含国际专利公布号WO2009/047356的SEQ ID NO:4、15、26、37、48以及59(分别为本文中的SEQ ID NO:443、454、465、476、487以及498)的CDR的抗骨硬化蛋白抗体、或包含国际专利公布号WO 2010/130830的SEQ ID NO:135-143、153-161、或171-179中的至少一者(分别为本文中的SEQ ID NO:745-753、763-771、781-789)的氨基酸序列的抗骨硬化蛋白抗体。
或者,本文所述的方法包括施用除抗骨硬化蛋白抗体以外的骨硬化蛋白抑制剂。此类药剂可对SOST或骨硬化蛋白直接或间接起作用。涵盖用于本文所述的方法的骨硬化蛋白抑制剂包括美国专利公布号2003/0229041(特此整个公开内容以引用的方式并入,尤其着重地描述了骨硬化蛋白抑制剂)中所述的骨硬化蛋白抑制剂。例如,适用于调节SOST表达和骨硬化蛋白活性的药剂包括但不限于类固醇(如对应于美国专利公布号2003/0229041的式1的那些)、生物碱、萜类化合物、类肽以及合成化学物质。在一些实施方案中,SOST拮抗剂或激动剂可结合糖皮质激素受体。例如,地塞米松倾向于消除BMP-4和BMP-6对SOST表达的刺激作用。其它化学实体,包括糖皮质激素类似物、胆盐(如对应于美国专利公布号2003/0229041的式3的那些)以及前列腺素(如对应于美国专利公布号2003/0229041的式2的那些)也调节骨骼形态发生蛋白对SOST表达的作用,且涵盖使用于本文所述的方法中。
可根据本文所述的方法使用的骨硬化蛋白表达抑制剂包括但不限于抑制核酸,包括其药学上可接受的盐,例如钠盐。在一些实施方案中,如本文别处描述的抑制核酸选自由以下组成的组:反义寡核苷酸、核糖酶、外部引导序列(EGS)寡核苷酸、siRNA化合物、单链或双链RNA干扰(RNAi)化合物如siRNA化合物、修饰的碱基/锁定核酸(LNA)、拮抗分子(antagomir)、肽核酸(PNA)、以及与目标核酸的至少一部分杂交且调节其功能的其它寡聚化合物或寡核苷酸模拟剂。在一些实施方案中,抑制剂核酸为单链或双链的。在一些实施方案中,抑制核酸为反义寡核苷酸、修饰的碱基/锁定核酸(LNA)、肽核酸(PNA)、阿拉伯糖核酸(ANA)(如例如PCT公布号WO 99/67378中所述);2'-氟-D-阿拉伯糖核酸(FANA)(如例如Lon等人,Biochem.,41:3457-3467,2002以及Min等人,Bioorg.Med.Chem.Lett.,12:2651-2654,2002中所描述;其公开内容以全文引用的方式并入本文中);磷二酰胺吗啉代寡聚物(PMO)(例如Iverson,Curr.Opin.Mol.Ther.,3:235-238,2001;以及Wang等人,J.GeneMed.,12:354-364,2010中所描述;其公开内容以引用的方式全部并入本文中);乙烯桥联核酸(如例如国际专利公布号WO 2005/042777;Morita等人,Nucleic Acid Res.,增刊1:241-242,2001;Surono等人,Hum.Gene Ther.,15:749-757,2004;Koizumi,Curr.Opin.Mol.Ther.,8:144-149,2006;以及Horie等人,Nucleic Acids Symp.Ser(Oxf),49:171-172,2005中所描述;其公开内容以引用的方式全部并入本文中);2'-O,4'-C-乙烯桥联核酸、核糖酶、外部引导序列(EGS)寡核苷酸、微RNA(miRNA)、小的临时RNA(stRNA)、以及单链或双链RNA干扰(RNAi)化合物或siRNA。在一些实施方案中,抑制核酸包含至少一个核苷酸和/或核苷修饰(例如具有修饰的骨架或修饰的糖部分的寡聚核酸)。
用于本文所述的方法中的特定骨硬化蛋白抑制剂(例如抗骨硬化蛋白抗体或抗体片段)的活性可以多种方式测量,包括上述用于检测骨骼矿物含量或骨骼密度增加的方法。骨硬化蛋白抑制剂调节骨骼质量的能力可由体重或利用其它方法计算(参见Guinness-Hey,Metab.Bone Dis.Relat.Res.,5:177-181(1984))。本领域中使用动物和特定的动物模型测试医药组合物和方法对例如骨质流失、骨吸收、骨形成、骨骼强度或骨矿化参数的作用。此类模型的实例包括切除卵巢的大鼠模型(Kalu,Bone and Mineral,15:175-192(1991);Frost以及Jee,Bone and Mineral,18:227-236(1992);以及Jee以及Yao,J.Musculoskel.Neuron.Interact.,1:193-207(2001))。本文所述的测量骨硬化蛋白结合剂活性的方法还可用于测定其它骨硬化蛋白抑制剂的功效。
或者,可基于调节骨骼标记物含量的能力选择骨硬化蛋白抑制剂。骨骼标记物为骨骼重塑过程中产生的产物且由骨骼、骨母细胞和/或破骨细胞释放。骨吸收和/或骨形成“标记物”含量的波动暗示骨骼重塑/塑造的变化。国际骨质疏松症基金会(IOF)推荐使用骨骼标记物监测骨骼密度疗法(参见例如Delmas等人,Osteoporos Int.,增刊.6:S2-17(2000),以引用的方式并入本文中)。指示骨吸收(或破骨细胞活性)的标记物包括例如C-端肽(例如1型胶原蛋白的C末端端肽(CTX)或血清交联的C-端肽)、N-端肽(1型胶原蛋白的N末端端肽(NTX))、脱氧吡啶啉(DPD)、吡啶啉、尿羟脯氨酸、半乳糖羟赖氨酸、以及酒石酸盐抗性酸性磷酸酶(例如血清酒石酸盐抗性酸性磷酸酶同功异型物5b)。骨形成/矿化标记物包括但不限于骨骼特异性碱性磷酸酶(BSAP)、I型原胶原的N末端和C末端延伸释放的肽(P1NP、PICP)、以及骨钙素(OstCa)。数种试剂盒可自商业上购得用于检测并且定量临床样品(如尿和血液)中的标记物。
施用途径
骨硬化蛋白抑制剂优选以可包含载体、赋形剂或稀释剂的生理学上可接受(例如医药)组合物形式施用给受试者。应了解,本文所述的骨硬化蛋白抑制剂(例如抗骨硬化蛋白抗体或抗体片段)可用于制备使用本文公开的任何剂量和/或时机方案施用的药剂。医药组合物和治疗方法公开于美国专利公布号20050106683和2007/110747中,其以引用的方式并入本文中。“生理学上可接受”指分子实体和组合物在施用给人时并不产生过敏性或类似的不良反应。另外,施用给受试者的组合物可以含有超过一种骨硬化蛋白抑制剂(例如两种抗骨硬化蛋白抗体、或骨硬化蛋白结合剂以及合成的化学骨硬化蛋白抑制剂)或骨硬化蛋白抑制剂与一或多种具有不同作用机制的治疗剂组合。
适用于多种施用途径的组合物和制剂的研发在本领域中为熟知的且讨论于美国专利公布号2007/0110747中,施用途径包括例如皮下、经口、胃肠外、静脉内、鼻内以及肌肉内施用。例如,在某些环境中,希望皮下、胃肠外、静脉内、肌肉内或甚至腹膜内递送包含骨硬化蛋白结合剂的医药组合物。此类方法对所属领域的技术人员为熟知的,其中一些进一步描述于例如美国专利号5,543,158、5,641,515以及5,399,363中。适于可注射用途的说明性医药形式包括无菌水溶液或分散液和临时制备无菌可注射溶液或分散液的无菌散剂(例如参见美国专利号5,466,468)。在所有情况下,所述形式必须为无菌的且必须为达到存在可容易注射性(即,无过度粘性以防穿过注射器)的程度的流体。
在一个方面,骨硬化蛋白抑制剂(例如抗骨硬化蛋白抗体或抗体片段)全身性施用。在一个实施方案中,对于水溶液形式的胃肠外施用,所述溶液必要时应合适地缓冲,且所述液体稀释剂首先用足够生理盐水或葡萄糖变得等张。这些特定水溶液尤其适于静脉内、肌肉内、皮下以及腹膜内施用。例如,一个剂量可溶解于1ml等张的NaCl溶液,且添加至1000ml皮下灌注流体或注射在建议的输注部位(参见例如Remington's PharmaceuticalSciences,第15版,Mack Pub.Co.,Easton,PA,第1035-1038页和第1570-1580页)。剂量和施用频率的一些变化可取决于所治疗受试者的病状;患者的年龄、身高、体重以及总体健康状况;以及任何副作用的存在而发生。另外,包含骨硬化蛋白结合剂的医药组合物可连同提供关于使用此类医药组合物的说明书的包装材料一起而置放在容器(例如小瓶或预填充注射器)内。一般来说,此类说明书将包括有形的表达,所述表达描述试剂浓度,并且在某些实施方案内,描述可能为复原医药组合物所必需的赋形剂成分或稀释剂(例如水、生理盐水或PBS)的相对量。
在另一方面,局部施用给受试者骨硬化蛋白抑制剂。在一些或任何实施方案中,骨硬化蛋白抑制剂(例如抗骨硬化蛋白抗体或抗体片段)根据疾病而施用至患病牙龈、骨骼或牙齿区域。在此方面,骨硬化蛋白抑制剂(例如抗骨硬化蛋白抗体或抗体片段)任选地通过例如含有骨硬化蛋白抑制剂以及适当载体的注射器直接注射至牙龈组织中和/或施用于牙周袋。
对于局部施用方面(如直接皮下注射骨硬化蛋白抑制剂至受试者的患病牙龈区域或患病牙周袋中),骨硬化蛋白抑制剂任选地以约0.1mg至约20mg的量施用给受试者。在一些实施方案中,骨硬化蛋白抑制剂直接施用至受感染区域,施用量为约0.1mg、0.5mg、1mg、2mg、3mg、4mg、5mg、6mg、7mg、8mg、9mg、10mg、11mg、12mg、13mg、14mg、15mg、16mg、17mg、18mg、19或约20mg。剂量以任何间隔施用,如每周多次(例如每周两次或三次)、每周一次、每两周一次、每三周一次、或每四周一次。在一些或任何实施方案中,每周两次施用约0.1mg至约20mg范围内的剂量的骨硬化蛋白抑制剂(例如抗骨硬化蛋白抗体或抗体片段)。抑制剂的量任选地沿受感染区域的片区以分次剂量施用,例如利用多个注射液。
在一些或任何实施方案中,骨硬化蛋白抑制剂(例如抗骨硬化蛋白抗体或抗体片段)并入凝胶、网状物、基质或胶原蛋白海绵中,嵌入牙齿植入物或骨移植物中,或涂布在植入物上。植入物可为受试者的自身牙齿(例如因外伤而丢失)的再植入或假体植入物(由例如塑料、陶瓷、金属制成或如WO 2004/074464中所述由干细胞制成)。
术语“网状物”意指呈任何形式的任何材料,包括例如打结、编织(braided)、挤出、冲压、编结、编织(woven)、非编织或其它形式,且可包括具有实质上规则和/或不规则图案的材料。可使用非编织网状物的实例,包括电纺材料(关于制备电纺奈米纤维材料的评论,参见Zheng-Ming Huang等人,Composites Science and Technology,2003,63:2223-2253)。网状物可为但不限于交联纤维网状物、奈米纤维网状物、网状物织物、生物可降解的聚合物网状物或任何上述者的组合。网状物可为不可降解的、可降解的或生物可降解的。可降解的网状物可为可经由非生物方式(例如水解或光解作用)降解的网状物。在不同的实施方案中,生物可降解的网状物为可由生物系统通过细胞或消化酶作用或经由生物分子氧化而分解的一类网状物。
用于经口递送抗体的示例性凝胶制剂物描述于WO2010/1004179中,其公开内容以引用的方式并入本文中。在一些实施方案中,凝胶为由合成或天然起源的高分子量生物相容的弹性聚合物制成的水凝胶。水凝胶的合乎要求的性质为在人体内快速响应机械应力、尤其剪切和荷载的能力。涵盖获自天然来源的水凝胶,因为其对于体内应用更可能为生物可降解的且生物相容的。适合的水凝胶包括天然水凝胶,例如像明胶;胶原蛋白;丝;弹性蛋白;纤维蛋白以及多糖衍生的聚合物;葡甘露聚糖凝胶;透明质酸;多糖,如交联的含羧基的多糖,或其组合。合成的水凝胶包括但不限于由聚乙烯醇形成的那些;丙烯酰胺,如聚丙烯酸和聚(丙烯睛-丙烯酸);聚氨基甲酸酯;聚乙二醇(例如PEG 3350、PEG 4500、PEG 8000);硅酮;聚烯烃,如聚异丁烯和聚异戊二烯;硅酮与聚氨基甲酸酯的共聚物;氯丁橡胶;丁腈橡胶;硫化橡胶;聚(N-乙烯基-2-吡咯烷酮);丙烯酸酯,如聚(甲基丙烯酸2-羟基乙酯)和丙烯酸酯与N-乙烯基咯烷酮的共聚物;N-乙烯基内酰胺;聚丙烯腈或其组合。水凝胶材料可进一步按需要交联以提供进一步强度。不同类型的聚氨基甲酸酯的实例包括热塑性或热固性聚氨基甲酸酯、脂族或芳族聚氨基甲酸酯、聚醚型氨基甲酸酯、聚碳酸酯-氨基甲酸酯或硅酮聚醚-氨基甲酸酯、或其组合。
在不同的实施方案中,不是直接将骨硬化蛋白抑制剂混合于凝胶中,而是将装载骨硬化蛋白抑制剂的微球体分散在凝胶内。在一个实施方案中,微球体提供骨硬化蛋白抑制剂的持续释放。在又一个实施方案中,生物可降解的凝胶阻止微球体释放骨硬化蛋白抑制剂;微球体因此在其自凝胶释放之前并不释放骨硬化蛋白抑制剂。例如,凝胶可布署在靶组织部位(例如牙槽嵴)周围。
本发明还涵盖使用粘附凝胶剂以限制骨硬化蛋白抑制剂的分散。凝胶剂可布署于例如牙周袋、牙齿、牙槽骨中或布署于周围的牙龈组织中。
在一些或任何实施方案中,骨硬化蛋白抑制剂配制成糊状物、药膏、蜡、洗剂、冲洗液、有/无增积剂的干燥散剂以及本领域已知的局部施用的不同的其它形式。骨硬化蛋白抑制剂还可以散剂或喷洒溶液或漱口溶液形式局部递送。或者,骨硬化蛋白抑制剂并入伤口敷料、护垫、纱布、或施加于所关注的患病区域(例如患病牙龈区域或牙周袋)的其它装置,所述骨硬化蛋白抑制剂自所述装置转移至所关注的患病区域。
组合疗法
通过组合两种或两种以上靶向相同病原体或生物化学路径的药剂的病理学治疗相对于单独使用治疗上有关的剂量的各药剂有时产生更高的功效和减小的副作用。在一些情况下,药物组合的功效相加(组合的功效近似等于各药物单独作用的总和),但在其它情况下,作用可为协同的(组合功效大于单独给予的各药物的作用的总和)。如本文所使用,术语“组合疗法”意指两种化合物可以同时的方式(例如并行)递送,或其中一种化合物首先施用,接着例如相继施用第二药剂。所要结果可为剂量接受者中一或多种症状的主观减轻或客观可识别的改善。
在一些实施方案中,施用骨硬化蛋白抑制剂(例如抗骨硬化蛋白抗体或抗体片段)与使用支持骨骼再生长的材料组合,所述材料如骨移植物、骨粉、骨碎片、去矿化骨基质、骨骼支架、修复体、金属稳定剂或骨骼支架物质,其包含一或多种聚合物、陶瓷、牙骨质以及基于磷酸钙的骨骼移植物取代物。本领域中已知此类材料的许多变体。
在一些或任何实施方案中,本文所述的方法或用途包括在施用骨硬化蛋白抑制剂(例如抗骨硬化蛋白抗体或抗体片段)之前向受试者施用治疗牙周病的标准护理疗法。例如,在一些实施方案中,治疗牙周病的标准护理疗法为选自由和/或化学改性的四环素-3(CMT-3)组成的组的治疗剂。在一些实施方案中,标准护理疗法包含受试者感染区域的口冲洗法和/或刮牙术以及牙龈上及/或牙龈下清创术(例如移除微生物牙菌斑及牙垢)。在一些实施方案中,标准护理包含在施用骨硬化蛋白抑制剂之前进行口冲洗法和/或刮牙术以及感染区域清创术与Periostat和/或CMT-3的组合。在一些实施方案中,所述方法包括施用标准护理疗法并行施用骨硬化蛋白抑制剂。在其它实施方案中,标准护理疗法相继施用。例如,标准护理疗法可在施用给受试者骨硬化蛋白抑制剂之前1天、2天、3天、4天、5天、6天、1周、2周、3周、4周、6周、8周、10周、12周或更长时间来施用。在优选实施方案中,在施用骨硬化蛋白抑制剂之前,受试者的牙周病进展减缓、停止或逆转。
在一些或任何实施方案中,本文所述的方法或用途进一步包含施用抗生素,如选自由以下组成的组的抗生素:阿莫西林、盐酸四环素、多西环素、米诺霉素、阿奇霉素、罗红霉素、莫西沙星、环丙沙星以及甲硝哒唑。在一些实施方案中,所述方法或用途包含在施用给受试者骨硬化蛋白抑制剂之前施用给受试者抗生素。在其它实施方案中,所述方法或用途包含与施用骨硬化蛋白抑制剂并行施用给受试者抗生素。
在一些实施方案中,施用骨硬化蛋白抑制剂(例如抗骨硬化蛋白抗体或抗体片段)以及适用于治疗骨骼矿物密度减小或骨骼缺陷的第二骨骼增强治疗剂。在一些实施方案中,骨骼增强治疗剂选自由以下组成的组:抗再吸收药物、成骨剂、雌激素受体调节剂(包括但不限于雷诺昔芬、巴多昔芬以及拉索昔芬)以及对破骨细胞具有抑制作用的药物。在一些实施方案中,第二骨骼增强剂选自由以下组成的组:双膦酸盐(包括但不限于阿仑膦酸钠()、利塞膦酸盐、伊班膦酸钠以及唑来膦酸);雌激素或雌激素类似物;抗RANK配体(RANKL)抗体(例如)或RANKL抑制剂;维生素D或维生素D衍生物或其模拟物;钙来源、替勃龙、降钙素、骨化三醇;以及激素代替疗法。在一些实施方案中,第二骨骼增强剂包括但不限于副甲状腺素(PTH)或其肽片段、PTH相关蛋白质(PTHrp)、骨骼形态发生蛋白、成骨素、NaF、PGE2激动剂、士他汀、雷奈酸锶、抗DKK1抗体或抑制剂。在一些实施方案中,第二骨骼增强剂为(特立帕肽)、
在不同实施方案中,牙周病治疗计划包括在骨硬化蛋白抑制剂积极治疗之后进行定期支持性跟踪疗法。在一些实施方案中,本文所述的方法或用途任选地包含进行选自由机械清创术、口腔卫生增强(例如定期专业清洁(即每6个月)、日常刷洗以及清牙垢)以及施用抗生素组成的组的支援性跟踪疗法。
在一些实施方案中,采用本文所述的骨硬化蛋白抑制剂的组合疗法可在施用另外的一种或多种治疗剂(例如抗生素或第二骨骼增强剂)之前或之后,间隔范围为数分钟至数周。例如,分开的模态在彼此的约24小时内、例如在彼此的约6-12小时内或在彼此的约1-2小时内或在彼此的约10-30分钟内施用。在一些情况下,可能希望显著延长治疗期,其中不同模态的各自施用之间间流逝数天(2、3、4、5、6或7天)至数周(1、2、3、4、5、6、7或8周)。尤其涵盖组合疗法的一种或两种药剂/疗法的重复治疗。
维持治疗方案
还涵盖在维持方案中使用第二骨骼增强剂和/或骨硬化蛋白抑制剂以例如预防或减缓牙槽骨的一或多个以下参数的损失:骨骼矿物密度、牙槽骨高度、牙槽骨质量、牙槽骨体积以及牙槽骨矿物含量。在此方面,本文所述的方法或用途任选地包含施用有效维持骨骼矿物密度、牙槽骨高度、牙槽骨质量、牙槽骨体积以及牙槽骨矿物含量的一或多个量的第二骨骼增强剂,维持期为骨硬化蛋白抗体治疗期结束后约1周至约5年。例如,在一些实施方案中,本文所述的方法或用途包含施用给受试者第二骨骼增强剂持续的维持期为约至少约1周、2周、3周、4周、5周、6周、7周、8周、9周、10周、11周、12周、3个月、13周、14周、15周、16周、4个月、17周、18周、19周、20周、5个月、21周、22周、23周、24周、6个月、25周、26周、27周、28周、7个月、29周、30周、31周或更长时间(例如8个月、9个月、10个月、11个月、1年、15个月、18个月、2年、3年、4年、5年或更长时间(例如受试者一生)。在一些实施方案中,维持期为约6-12周。在一些实施方案中,维持期为约4-12周或约1-3个月。在一些实施方案中,维持期为约12-20周或约3-5个月。在一些实施方案中,维持期为约20-32周或约5-8个月。在一些实施方案中,维持期为约24-36周或约6-9个月。在一些实施方案中,维持期为约1年、约2年、约3年、约4年、约5年或更长时间。“维持”牙槽骨包括维持接受骨硬化蛋白抑制剂治疗的受试者所经受的类似水平的牙槽骨参数。
类似地,本文所述的方法或用途任选地包含随后施用对骨骼矿物密度、牙槽骨高度、牙槽骨质量、牙槽骨体积以及牙槽骨矿物含量有效的一或多个量的骨硬化蛋白抑制剂,维持期为治疗期结束后至少约至少约1周、2周、3周、4周、5周、6周、7周、8周、9周、10周、11周、12周、3个月、13周、14周、15周、16周、4个月、17周、18周、19周、20周、5个月、21周、22周、23周、24周、6个月、1年、2年、3年、4年、5年或更长时间(例如受试者一生)。在一些实施方案中,维持期为约6-12周。在一些实施方案中,维持期为约4-12周或约1-3个月。在一些实施方案中,维持期为约12-20周或约3-5个月。在一些实施方案中,维持期为约20-32周或约5-8个月。在一些实施方案中,维持期为约24-36周或约6-9个月。在一些实施方案中,维持期为约1年、约2年、约3年、约4年、约5年或更长时间。
试剂盒
包含骨硬化蛋白抑制剂(例如抗骨硬化蛋白抗体或抗体片段)的医药组合物可连同提供关于使用此类医药组合物的说明书的包装材料一起置放在容器(例如小瓶或注射器)内。一般来说,此类说明书将包括有形表达,所述表达描述骨硬化蛋白抑制剂浓度,以及在某些实施方案内,描述可能为复原医药组合物所必需的赋形剂成分或稀释剂(例如水、生理盐水或PBS)的相对量。
本发明在下列实施例中进一步描述。以下实施例仅用于说明本发明,且无论如何不旨在限制本发明的范围。
实施例
实施例1
本实施例描述适用于表征抗骨硬化蛋白抗体的中和活性的不同的基于细胞的中和测定。
基于MC3T3细胞的矿化测定-使用抗坏血酸和B-甘油磷酸盐诱发MC3T3-E1-BF细胞分化,从而导致矿物沉积。一种示例性筛选方案在96孔格式中包括在第1天接种细胞,接着在12天时间内,更换7次培养基,大多数矿物沉积在最后18小时内发生。矿物沉积的具体时间和程度可以部分地取决于所使用的特定血清批号而变化。如细胞培养实验领域中一般所熟知,对照实验将允许虑及所述变量。对于统计分析(使用MS Excel和JMP),可依次使用单向ANOVA和杜氏比较(Dunnett's comparison)来确定组之间的差异。当P值小于0.05(P<0.05)时,数据集的组平均值被视为显著不同。
用于MC3T3-E1-BF细胞扩增的细胞培养如下进行。细胞培养在37℃和5%CO2下进行。出于筛选骨硬化蛋白中和抗体的目的,可产生细胞库。通过在37℃水浴中搅动,解冻一小瓶冷冻的MC3T3-E1-BF细胞。将解冻的细胞投入50ml试管中的10ml扩增培养基(α-MEM/10%FBS/PenStrepGlu)中,且平缓地离心5分钟。随后使细胞再悬浮于4mlα-MEM/10%FBS/PenStrepGlu中。在使用台盼蓝和血球计确定细胞数目之后,将1x106个细胞接种于在一个T175烧瓶中的50mlα-MEM/10%FBS/PenStrepGlu培养基中。
当此继代融合(约7天)时,用胰蛋白酶/EDTA(0.05%胰蛋白酶;0.53mM EDTA)使细胞进行胰蛋白酶处理,平缓地离心5分钟,并且随后再悬浮于5mlα-MEM/10%FBS/PenStrepGlu中。在使用台盼蓝和血球计确定细胞数目之后,接种细胞,每一个T175烧瓶将1x106个细胞接种于50mlα-MEM/10%FBS/PenStrepGlu培养基中。用于接种的T175烧瓶的数目此时取决于可利用的总细胞数目和将用于下一继代所要的烧瓶数目。
当此继代融合(约3-4天)时,用胰蛋白酶/EDTA(0.05%胰蛋白酶;0.53mM EDTA)使细胞进行胰蛋白酶处理,平缓地离心5分钟,并且随后再悬浮于5mlα-MEM/10%FBS/PenStrepGlu中。在使用台盼蓝和血球计确定细胞数目之后,接种细胞,每一个T175烧瓶将1x106个细胞接种于50mlα-MEM/10%FBS/PenStrepGlu培养基中。用于接种的T175烧瓶的数目此时取决于可利用的总细胞数目和将用于下一继代所要的烧瓶数目。
当此继代融合(约3-4天)时,用胰蛋白酶/EDTA(0.05%胰蛋白酶;0.53mM EDTA)使细胞进行胰蛋白酶处理,平缓地离心5分钟,并且随后再悬浮于5mlα-MEM/10%FBS/PenStrepGlu中。在使用台盼蓝和血球计确定细胞数目之后,接种细胞,每一个T175烧瓶将1x106个细胞接种于50mlα-MEM/10%FBS/PenStrepGlu培养基中。用于接种的T175烧瓶的数目此时取决于可利用的总细胞数目和将用于下一继代所要的烧瓶数目。以1-2x106个活细胞/ml在90%FBS/10%DMSO中冷冻额外的细胞。
当此继代融合(约3-4天)时,用胰蛋白酶/EDTA(0.05%胰蛋白酶;0.53mM EDTA)使细胞进行胰蛋白酶处理,平缓地离心5分钟,并且随后再悬浮于5mlα-MEM/10%FBS/PenStrepGlu中。在使用台盼蓝和血球计确定细胞数目之后,以1-2x106个活细胞/ml在90%FBS/10%DMSO中冷冻细胞。此“最后继代”的冷冻细胞为用于筛选测定的继代。
用于矿化MC3T3-E1-BF细胞的细胞培养如下进行。细胞培养在37℃和5%CO2下进行。在矿化细胞培养物程序期间,需要将温度和CO2波动%最小化。通过在37℃水浴中搅动,解冻适当数目的如上所述制备的“最后继代”小瓶。将解冻的细胞投入50ml试管中的10ml扩增培养基(α-MEM/10%FBS/PenStrepGlu)中,并且平缓地离心5分钟。随后使细胞再悬浮于4mlα-MEM/10%FBS/PenStrepGlu中。在使用台盼蓝和血球计确定细胞数目之后,在胶原蛋白I涂布的96孔板上,将每孔2500个细胞接种于200微升扩增培养基中(Becton DickinsonLabware,目录号354407)。
示例性细胞培养程序如下。指示接种细胞起始日为星期三。如果使用所述周中的不同的一天作为用于接种细胞的起始日,则所述日将触发如下文指示的整个方法期间移除和添加培养基的日程。例如,如果在星期二接种细胞,则不应在第一个星期五和星期六,也不应在第二个星期五和星期六,移除和添加培养基。在星期二起始情况下,应在最后的星期日制备板用于钙测定。在星期三接种细胞,2500个细胞接种于200μl扩增培养基中。在星期四,移除所有扩增培养基且添加200μl分化培养基。在星期五,移除100μl培养基且添加100μl新鲜的分化培养基。在星期一,移除100μl培养基且添加100μl新鲜的分化培养基。在星期二,移除100μl培养基且添加100μl新鲜的分化培养基。在星期三,移除100μl培养基且添加100μl新鲜的分化培养基。在星期四,移除100μl培养基且添加100μl新鲜的分化培养基。在星期五,移除100μl培养基且添加100μl新鲜的分化培养基。在下一个星期一,如下制备板用于钙测定:用10mM Tris,HCl(pH 7-8)洗涤板一次。在通风橱下作业,每孔添加200μl 0.5NHCl。随后在-80℃下冷冻板。恰好在测量钙之前,冷冻-解冻板两次,并且随后使用多通道吸移管湿磨来分散板的内容物。随后在4℃下使板的内容物沉降30分钟,此时移除适量上清液以使用市售钙试剂盒测量钙。示例性且非限制性试剂盒为钙(CPC)Liquicolor,目录号0150-250,Stanbio Laboratory,Boerne,TX。
在此基于细胞的测定中,骨硬化蛋白抑制导致且包括矿物沉积的一系列事件中的一个或多个(即骨硬化蛋白抑制矿化)。因此,在特定细胞培养实验中包括骨硬化蛋白的实验中,在第一个星期四起始和此后的每个饲喂日,向培养基中添加重组骨硬化蛋白。在测试抗骨硬化蛋白抗体中和骨硬化蛋白的能力,即通过中和骨硬化蛋白抑制矿化的能力来允许矿化的情况下,在第一个星期四起始和此后的每个饲喂日,向培养基中添加抗体。在37℃下在分化培养基中与重组骨硬化蛋白一起预孵育抗体45-60分钟,且随后使用所述培养基饲喂细胞。
上述为针对MC3T3-E1-BF细胞的12天矿化方案。原始MC3T3-E1细胞的矿化受重组骨硬化蛋白抑制,并且使用抗骨硬化蛋白中和抗体,例如包含SEQ ID NO:245-247和78-80的CDR的抗骨硬化蛋白抗体封闭这种抑制。基于细胞的中和测定进一步描述于美国专利公布号7,592,429的例如实施例8处(特此其基于细胞的中和测定的描述以引用的方式并入)。
骨骼特异性碱性磷酸酶酸测定-示例性骨骼特异性碱性磷酶酸测定描述于国际专利公布号WO 2008/115732和美国专利号7,744,874(特此其基于细胞的中和测定的描述以引用的方式并入)。示例性方案如下。在96孔组织培养板的补充有5%胎牛血清的MEM培养基中按3000-5000个细胞/孔接种C2C12细胞(ATCC,CRL 1772)。在37℃下在5%CO2中孵育板隔夜。在0.5X Wnt3a调节培养基(如WO 2008/115732中所述制备)中稀释抗体至不同的最终浓度。自接种的细胞移除培养基,且添加预混合的抗体-BMP4-骨硬化蛋白溶液(人或猕猴)(150μl),得到30μg/ml至0.5μg/ml的抗体最终浓度,25ng/ml的最终BMP-4浓度,1.0μg/ml的最终骨硬化蛋白蛋白质浓度,且调节培养基为0.5X浓度。随后在37℃下在5%CO2中孵育板72小时。自细胞移除培养基,用PBS洗涤一次,且在-80℃与37℃之间交替冷冻和解冻三次。通过添加碱性磷酸酶底物(1-步PNPP,Pierce#37621)(150μl/孔)测量碱性磷酸酶活性。在室温下孵育细胞板60分钟,此时在405nm下测量光密度(OD)以确定碱性磷酸酶活性。可以使用例如具S型4参数拟合方程的SigmaPlot Regression Wizard进行IC50计算。
BMP2诱发的MC3T3细胞矿化测定-MC3T3细胞中的示例性BMP2诱发的矿化测定描述于国际专利公布号WO 2009/047356(特此其基于细胞的中和测定的描述以引用的方式并入)。简单地说,将MC3T31b细胞接种于96孔板的100μl测定培养基(无G418的维持培养基)中(例如6x103个细胞/孔或2x103个细胞/孔)并孵育三天达到融合。改变测定培养基,且添加欲测试的化合物与10mM b-甘油磷酸盐和50μM抗坏血酸。在添加至细胞中之前,在室温下在独立板上预孵育骨硬化蛋白和候选抗体两小时。在施加骨硬化蛋白-抗体混合物之前,向测定96孔板中施加2.1或2.8nM BMP-2(R&D Systems,目录号355-BM-010)。孵育细胞14天。在孵育结束时,用200μl PBS/孔洗涤细胞两次,向各孔中添加50μl 0.5M HCl,且在-20℃下冷冻板至少24小时。在室温下解冻板2小时以供测试。将十10μl各孔转移至新板中,且暴露于钙工作溶液(1:5)(200μl)。在5-30分钟孵育期之后,在微板读取器上在595nm下测量光密度。根据标准曲线将吸光度转换成钙的微克数,从而测定BMP-2诱发的矿化的程度。
基于细胞的wnt信号传导测定-采用上顶边(super top flash;STF)报告蛋白的示例性基于细胞的信号传导测定描述于国际专利公布号WO 2009/047356中。用以下对HEK293细胞进行转染:对于对照孔,pcDNA3+(480ng);SuperTopFlash(STF)(20ng);以及phRL-CMV(0.5ng),并且对于Wnt1处理孔,pcDNA-wnt1(20ng);pcDNA3+(460ng);SuperTopFlash(STF)(20ng);以及phRL-CMV(0.5ng)。将质粒与稀释于50μl中的1.6μlLipofectamine 2000混合,且在施加至细胞之前在室温下孵育30分钟。一旦施加,在37℃下在5%CO2中孵育细胞5小时。
将抗体与SOST一起预混合以生成一系列稀释液。各稀释液制备1ml培养基,并且在移除转染混合物后,向各孔中添加450μl。细胞与抗体-SOST混合物一起孵育18-20小时。孵育结束时,移除培养基,且向溶解细胞中添加300μl 1X被动溶解缓冲液(Promega,目录号E194A)。随后使用Dual-Glo荧光素酶系统(Promega,目录号E2940)和30μl溶解产物一式两份测量荧光素酶活性。典型地,使用30μl Dual-Glo荧光素酶(荧火虫荧光素酶;对于STF)和30μl Dual-Glo Stop与Glo(海肾荧光素酶;对于转染效率对照)底物。用Mithras LB940仪器(Berthold Technologies)测量发光信号。计算荧火虫与海肾荧光素酶的比率。通过将无SOST的Wnt1值设定为1来表示最终结果。测定的另外的细节提供于国际专利公布号WO2009/047356中。
实施例2—
以下实施例说明骨硬化蛋白抑制剂,即抗骨硬化蛋白单克隆抗体(Scl-Ab)在大鼠牙周病模型中增强牙槽骨修复的能力。
大鼠牙周炎模型:通过如先前所述的结扎置放,在大鼠中诱发实验牙周病(Jin Q等人,2007.J Periodontol 78:1300-1308;Graves,DT等人,2008.J Clin Periodontol35:89-105;其公开内容以引用的方式全部并入本文中)。简单地说,用氯胺酮和噻榛(83/17比率)使雄性Sprague Dawley大鼠(体重约300-350g,Harlan Laboratory,IN)麻醉。随后环绕位于小颚的一侧的磨牙的颈部分(恰在牙龈上方)固定棉缝合线(3.0)以允许进行正常咀嚼。每周评估结扎三次,自顶端平缓地移入牙龈缝中以确保龈下位置,且必要时更换。
微电脑断层(μCT)扫描和分析:在指定时间点,处死大鼠。解剖小颚且置放于10%中性缓冲福尔马林中48-72小时。在70%乙醇中通过锥形射束微CT系统(GE HealthcareBioSciences)扫描固定的未去矿化大鼠小颚。线性且测定体积的分析是基于先前开发的方法(Park CH等人,2007.J Periodontol 78:273-281)。简单地说,扫描各上颌试样,且使用μCT系统在18×18×18-μm三维像素下重建。使用三维(3-D)体积观测器和分析软件(Microview Analysis,GE Healthcare)作为3-D与2-D可视化和定量的工具。通过测量上颌第二磨牙的自牙骨质-牙轴质接面(CEJ)至牙槽骨嵴(ABC)的距离鉴别垂直的线性骨质流失。就体积分析而论,使用第一磨牙的最近中根(m-M1)、第三磨牙的最远中根(d-M3)、分叉的顶盖、M1-M3的根尖作为评估上颌牙槽骨的可重现的标志。在前视图(coronal view)上以规则间距(平均值,8个数据切片)绘制二维感兴趣区域(ROI)且重建为3-D结构以定量体积参数、骨骼体积分数(BVF)以及骨骼矿物密度(BMD;mg/cc)。
统计分析:使用GraphPad Prism(V.5.01)进行统计分析。通过单向方差分析(ANOVA)与Tukey多重比较事后检验在统计上评估线性且测定体积的骨骼测量的组之间的差异。数据以平均值+SE报告,且显著性水平设定为P≤0.05。
研究设计:使10至12周龄雄性Sprague-Dawley(SD)大鼠经受通过如上所述的结扎置放而诱发的实验牙周炎。在一个研究模式中,在结扎置放前三天,用生理盐水媒介物或Scl-Ab(剂量水平为25mg/kg)皮下注射动物(n=10只/组)一次。在结扎置放之后立即用生理盐水媒介物或Scl-Ab处理结扎的动物或其正常完整对照。通过每周皮下注射两次给予Scl-Ab(剂量水平为25mg/kg)和其媒介物对照。分别在疾病诱发后两周和四周进行验尸。
在另一研究模式中,结扎诱发的实验牙周炎四周后,移除结扎后立即开始处理。用生理盐水媒介物或Scl-Ab(剂量水平为25mg/kg)每周皮下注射患实验牙周炎的动物(n=10只/组)或其正常完整对照两次。处理在疾病诱发停止后持续三周或六周,总研究持续时间为7周或10周。在Scl-Ab施用之前每周进行体重测量直至研究结束为止。分别在疾病诱发后七周和十周进行验尸。收集全血(用于血清测定)、小颚以及股骨。研究由密歇根大学(University of Michigan)的机构动物护理与使用委员会(Institution Animal Careand Use Committee)批准。
结果
上颌牙槽骨:图2和图3中阐述支持牙槽骨体积和密度的微CT测量。在整个研究过程(两周和四周)中置放结扎的研究模式中,与处理开始后两周和四周接受媒介物注射液的正常完整动物相比,正常完整动物组中的全身性Scl-Ab施用在骨骼体积分数(BVF)与骨骼矿物密度(BMD)方面均产生统计上显著增加。此外,接受全身性Scl-Ab注射液的结扎诱发的牙周病组显示BVF和BMD(虽然统计上不显著)值与两周和四周时间点接受媒介物注射液的疾病组相比增加(图2A和图2B)。
在置放后四周和处理开始前立即移除结扎的研究模式中,与正常完整动物组相比,实验牙周炎组中在疾病诱发期期间BVF和BMD显示在统计上显著减小。在疾病诱发停止后三周内,媒介物处理组中BVF和BMD反弹并且随后稳定直至研究结束为止。与接受媒介物注射液的动物组相比,实验牙周炎诱发后接受Scl-Ab处理的结扎动物在六周处理阶段始终展示改善的骨骼修复(即骨骼体积和密度值更高)。最重要的是,在处理六周后,BVF和BMD在用Scl-Ab处理的动物中比在媒介物处理的动物组中在统计上更高。此外,在10周研究结束时,骨骼体积分数和骨骼密度在Scl-Ab处理的疾病动物与媒介物处理的正常完整动物之间未发现统计性差异,表明Scl-Ab可有助于在牙周病后使牙槽骨再生至健康正常水平。
线性骨骼测量:牙槽骨高度是用微CT评估自第二磨牙的骨骼嵴至牙骨质-牙轴质接面测量(图4)。在置放后四周和处理开始前立即移除结扎的研究模式中,scl-Ab施用显示对线性骨骼修复(即增加牙槽骨高度)有一定作用。处理三周后,在结扎的第二磨牙部位,在Scl-Ab处理与媒介物组之间未观察到线性骨骼测量统计显着性。然而,在处理后六周时间点时,Scl-Ab处理显示线性骨骼修复增加,其中在结扎的第二磨牙部位处在媒介物和Scl-Ab处理组与媒介物组之间统计上显著差异明显(图4A至图4C)。
实验牙周炎诱发后六周全身性施用Scl-Ab与媒介物处理相比产生统计上更高的BVF和BMD值,以及与正常完整组相比统计上类似的骨骼测量。因此,如由BVF和BMD所测量,全身性Scl-Ab施用促使牙槽骨再生。Scl-Ab可有希望成为增强和/或加速口骨再生的治疗剂。
虽然本发明已在着重强调优选实施方案的情况下予以描述,但是显然所属领域的技术人员可使用优选化合物和方法的变化形式,并且预期本发明可以与本文具体描述的方式不同的方式来实践。因此,本发明包括如下文权利要求书所限定的本发明精神和范围内内所涵盖的所有修改。
序列表
<110> Li等人
<120> 用于治疗骨隙缺陷的方法
<130> 31173/46570
<160> 809
<170> PatentIn版本3.5
<210> 1
<211> 190
<212> PRT
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Gln Gly Trp Gln Ala Phe Lys Asn Asp Ala Thr Glu Ile Ile Pro Glu
1 5 10 15
Leu Gly Glu Tyr Pro Glu Pro Pro Pro Glu Leu Glu Asn Asn Lys Thr
20 25 30
Met Asn Arg Ala Glu Asn Gly Gly Arg Pro Pro His His Pro Phe Glu
35 40 45
Thr Lys Asp Val Ser Glu Tyr Ser Cys Arg Glu Leu His Phe Thr Arg
50 55 60
Tyr Val Thr Asp Gly Pro Cys Arg Ser Ala Lys Pro Val Thr Glu Leu
65 70 75 80
Val Cys Ser Gly Gln Cys Gly Pro Ala Arg Leu Leu Pro Asn Ala Ile
85 90 95
Gly Arg Gly Lys Trp Trp Arg Pro Ser Gly Pro Asp Phe Arg Cys Ile
100 105 110
Pro Asp Arg Tyr Arg Ala Gln Arg Val Gln Leu Leu Cys Pro Gly Gly
115 120 125
Glu Ala Pro Arg Ala Arg Lys Val Arg Leu Val Ala Ser Cys Lys Cys
130 135 140
Lys Arg Leu Thr Arg Phe His Asn Gln Ser Glu Leu Lys Asp Phe Gly
145 150 155 160
Thr Glu Ala Ala Arg Pro Gln Lys Gly Arg Lys Pro Arg Pro Arg Ala
165 170 175
Arg Ser Ala Lys Ala Asn Gln Ala Glu Leu Glu Asn Ala Tyr
180 185 190
<210> 2
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<212> PRT
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Asp Val Ser Glu Tyr Ser Cys Arg Glu Leu His Phe Thr Arg
1 5 10
<210> 3
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<212> PRT
<213> 智人
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Ser Ala Lys Pro Val Thr Glu Leu Val Cys Ser Gly Gln Cys Gly Pro
1 5 10 15
<210> 4
<211> 17
<212> PRT
<213> 智人
<400> 4
Trp Trp Arg Pro Ser Gly Pro Asp Phe Arg Cys Ile Pro Asp Arg Tyr
1 5 10 15
Arg
<210> 5
<211> 12
<212> PRT
<213> 智人
<400> 5
Leu Val Ala Ser Cys Lys Cys Lys Arg Leu Thr Arg
1 5 10
<210> 6
<211> 26
<212> PRT
<213> 智人
<400> 6
Cys Gly Pro Ala Arg Leu Leu Pro Asn Ala Ile Gly Arg Gly Lys Trp
1 5 10 15
Trp Arg Pro Ser Gly Pro Asp Phe Arg Cys
20 25
<210> 7
<211> 214
<212> PRT
<213> 家鼷鼠
<400> 7
Asp Val Gln Met Ile Gln Ser Pro Ser Ser Leu Ser Ala Ser Leu Gly
1 5 10 15
Asp Ile Val Thr Met Thr Cys Gln Ala Ser Gln Gly Thr Ser Ile Asn
20 25 30
Leu Asn Trp Phe Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Gly Ser Ser Asn Leu Glu Asp Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Arg Tyr Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Asp
65 70 75 80
Glu Asp Leu Ala Thr Tyr Phe Cys Leu Gln His Ser Tyr Leu Pro Tyr
85 90 95
Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Ala Asp Ala Ala
100 105 110
Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln Leu Thr Ser Gly
115 120 125
Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr Pro Lys Asp Ile
130 135 140
Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln Asn Gly Val Leu
145 150 155 160
Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr Tyr Ser Met Ser
165 170 175
Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg His Asn Ser Tyr
180 185 190
Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro Ile Val Lys Ser
195 200 205
Phe Asn Arg Asn Glu Cys
210
<210> 8
<211> 645
<212> DNA
<213> 家鼷鼠
<400> 8
gatgtccaga tgattcagtc tccatcctcc ctgtctgcat ctttgggaga catagtcacc 60
atgacttgcc aggcaagtca gggcactagc attaatttaa actggtttca gcaaaaacca 120
gggaaggctc ctaagctcct gatctatggt tcaagcaact tggaagatgg ggtcccatca 180
aggttcagtg gcagtagata tgggacagat ttcactctca ccatcagcag cctggaggat 240
gaagatctgg caacttattt ctgtctacaa catagttatc tcccgtacac gttcggaggg 300
gggaccaagc tggaaataaa acgggctgat gctgcaccaa ctgtatccat cttcccacca 360
tccagtgagc agttaacatc tggaggtgcc tcagtcgtgt gcttcttgaa caacttctac 420
cccaaagaca tcaatgtcaa gtggaagatt gatggcagtg aacgacaaaa tggcgtcctg 480
aacagttgga ctgatcagga cagcaaagac agcacctaca gcatgagcag caccctcacg 540
ttgaccaagg acgagtatga acgacataac agctatacct gtgaggccac tcacaagaca 600
tcaacttcac ccattgtcaa gagcttcaac aggaatgagt gttag 645
<210> 9
<211> 236
<212> PRT
<213> 家鼷鼠
<400> 9
Met Asn Thr Arg Ala Pro Ala Glu Phe Leu Gly Phe Leu Leu Leu Trp
1 5 10 15
Phe Leu Gly Ala Arg Cys Asp Val Gln Met Ile Gln Ser Pro Ser Ser
20 25 30
Leu Ser Ala Ser Leu Gly Asp Ile Val Thr Met Thr Cys Gln Ala Ser
35 40 45
Gln Gly Thr Ser Ile Asn Leu Asn Trp Phe Gln Gln Lys Pro Gly Lys
50 55 60
Ala Pro Lys Leu Leu Ile Tyr Gly Ser Ser Asn Leu Glu Asp Gly Val
65 70 75 80
Pro Ser Arg Phe Ser Gly Ser Arg Tyr Gly Thr Asp Phe Thr Leu Thr
85 90 95
Ile Ser Ser Leu Glu Asp Glu Asp Leu Ala Thr Tyr Phe Cys Leu Gln
100 105 110
His Ser Tyr Leu Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile
115 120 125
Lys Arg Ala Asp Ala Ala Pro Thr Val Ser Ile Phe Pro Pro Ser Ser
130 135 140
Glu Gln Leu Thr Ser Gly Gly Ala Ser Val Val Cys Phe Leu Asn Asn
145 150 155 160
Phe Tyr Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly Ser Glu
165 170 175
Arg Gln Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp
180 185 190
Ser Thr Tyr Ser Met Ser Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr
195 200 205
Glu Arg His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr
210 215 220
Ser Pro Ile Val Lys Ser Phe Asn Arg Asn Glu Cys
225 230 235
<210> 10
<211> 711
<212> DNA
<213> 家鼷鼠
<400> 10
atgaacacga gggcccctgc tgagttcctt gggttcctgt tgctctggtt tttaggtgcc 60
agatgtgatg tccagatgat tcagtctcca tcctccctgt ctgcatcttt gggagacata 120
gtcaccatga cttgccaggc aagtcagggc actagcatta atttaaactg gtttcagcaa 180
aaaccaggga aggctcctaa gctcctgatc tatggttcaa gcaacttgga agatggggtc 240
ccatcaaggt tcagtggcag tagatatggg acagatttca ctctcaccat cagcagcctg 300
gaggatgaag atctggcaac ttatttctgt ctacaacata gttatctccc gtacacgttc 360
ggagggggga ccaagctgga aataaaacgg gctgatgctg caccaactgt atccatcttc 420
ccaccatcca gtgagcagtt aacatctgga ggtgcctcag tcgtgtgctt cttgaacaac 480
ttctacccca aagacatcaa tgtcaagtgg aagattgatg gcagtgaacg acaaaatggc 540
gtcctgaaca gttggactga tcaggacagc aaagacagca cctacagcat gagcagcacc 600
ctcacgttga ccaaggacga gtatgaacga cataacagct atacctgtga ggccactcac 660
aagacatcaa cttcacccat tgtcaagagc ttcaacagga atgagtgtta g 711
<210> 11
<211> 443
<212> PRT
<213> 家鼷鼠
<400> 11
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Thr Pro Gly Ala
1 5 10 15
Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp His
20 25 30
Tyr Met Ser Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile
35 40 45
Gly Asp Ile Asn Pro Tyr Ser Gly Glu Thr Thr Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Thr Ala Thr Leu Thr Val Asp Lys Ser Ser Ser Ile Ala Tyr
65 70 75 80
Met Glu Ile Arg Gly Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Asp Tyr Asp Ala Ser Pro Phe Ala Tyr Trp Gly Gln Gly
100 105 110
Thr Leu Val Thr Val Ser Ala Ala Lys Thr Thr Pro Pro Ser Val Tyr
115 120 125
Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr Asn Ser Met Val Thr Leu
130 135 140
Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val Thr Val Thr Trp
145 150 155 160
Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr Phe Pro Ala Val Leu
165 170 175
Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr Val Pro Ser Ser
180 185 190
Thr Trp Pro Ser Glu Thr Val Thr Cys Asn Val Ala His Pro Ala Ser
195 200 205
Ser Thr Lys Val Asp Lys Lys Ile Val Pro Arg Asp Cys Gly Cys Lys
210 215 220
Pro Cys Ile Cys Thr Val Pro Glu Val Ser Ser Val Phe Ile Phe Pro
225 230 235 240
Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro Lys Val Thr
245 250 255
Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu Val Gln Phe Ser
260 265 270
Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr Gln Pro Arg
275 280 285
Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser Glu Leu Pro Ile
290 295 300
Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg Val Asn
305 310 315 320
Ser Pro Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys
325 330 335
Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro Lys Glu
340 345 350
Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile Thr Asp Phe
355 360 365
Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly Gln Pro Ala
370 375 380
Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr Asp Gly Ser Tyr
385 390 395 400
Phe Ile Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn Trp Glu Ala Gly
405 410 415
Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His Asn His His
420 425 430
Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys
435 440
<210> 12
<211> 1332
<212> DNA
<213> 家鼷鼠
<400> 12
gaggtccagc tgcaacagtc tggacctgaa ctggtgacgc ctggggcttc agtgaagata 60
tcttgtaagg cttctggata cacattcact gaccactaca tgagctgggt gaagcagagt 120
catggaaaaa gccttgagtg gattggagat attaatccct attctggtga aactacctac 180
aaccagaagt tcaagggcac ggccacattg actgtagaca agtcttccag tatagcctac 240
atggagatcc gcggcctgac atctgaggac tctgcagtct attactgtgc aagagatgat 300
tacgacgcct ctccgtttgc ttactggggc caagggactc tggtcactgt ctctgcagcc 360
aaaacgacac ccccatctgt ctatccactg gcccctggat ctgctgccca aactaactcc 420
atggtgaccc tgggatgcct ggtcaagggc tatttccctg agccagtgac agtgacctgg 480
aactctggat ccctgtccag cggtgtgcac accttcccag ctgtcctgca gtctgacctc 540
tacactctga gcagctcagt gactgtcccc tccagcacct ggcccagcga gaccgtcacc 600
tgcaacgttg cccacccggc cagcagcacc aaggtggaca agaaaattgt gcccagggat 660
tgtggttgta agccttgcat atgtacagtc ccagaagtat catctgtctt catcttcccc 720
ccaaagccca aggatgtgct caccattact ctgactccta aggtcacgtg tgttgtggta 780
gacatcagca aggatgatcc cgaggtccag ttcagctggt ttgtagatga tgtggaggtg 840
cacacagctc agacgcaacc ccgggaggag cagttcaaca gcactttccg ctcagtcagt 900
gaacttccca tcatgcacca ggactggctc aatggcaagg agttcaaatg cagggtcaac 960
agtccagctt tccctgcccc catcgagaaa accatctcca aaaccaaagg cagaccgaag 1020
gctccacagg tgtacaccat tccacctccc aaggagcaga tggccaagga taaagtcagt 1080
ctgacctgca tgataacaga cttcttccct gaagacatta ctgtggagtg gcagtggaat 1140
gggcagccag cggagaacta caagaacact cagcccatca tggacacaga tggctcttac 1200
ttcatctaca gcaagctcaa tgtgcagaag agcaactggg aggcaggaaa tactttcacc 1260
tgctctgtgt tacatgaggg cctgcacaac caccatactg agaagagcct ctcccactct 1320
cctggtaaat ga 1332
<210> 13
<211> 462
<212> PRT
<213> 家鼷鼠
<400> 13
Met Arg Cys Arg Trp Ile Phe Leu Phe Leu Leu Ser Gly Thr Ala Gly
1 5 10 15
Val Leu Ser Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Thr
20 25 30
Pro Gly Ala Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe
35 40 45
Thr Asp His Tyr Met Ser Trp Val Lys Gln Ser His Gly Lys Ser Leu
50 55 60
Glu Trp Ile Gly Asp Ile Asn Pro Tyr Ser Gly Glu Thr Thr Tyr Asn
65 70 75 80
Gln Lys Phe Lys Gly Thr Ala Thr Leu Thr Val Asp Lys Ser Ser Ser
85 90 95
Ile Ala Tyr Met Glu Ile Arg Gly Leu Thr Ser Glu Asp Ser Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Asp Asp Tyr Asp Ala Ser Pro Phe Ala Tyr Trp
115 120 125
Gly Gln Gly Thr Leu Val Thr Val Ser Ala Ala Lys Thr Thr Pro Pro
130 135 140
Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr Asn Ser Met
145 150 155 160
Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val Thr
165 170 175
Val Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr Phe Pro
180 185 190
Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr Val
195 200 205
Pro Ser Ser Thr Trp Pro Ser Glu Thr Val Thr Cys Asn Val Ala His
210 215 220
Pro Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val Pro Arg Asp Cys
225 230 235 240
Gly Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser Ser Val Phe
245 250 255
Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro
260 265 270
Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu Val
275 280 285
Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr
290 295 300
Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser Glu
305 310 315 320
Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys
325 330 335
Arg Val Asn Ser Pro Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile Ser
340 345 350
Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro
355 360 365
Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile
370 375 380
Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly
385 390 395 400
Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr Asp
405 410 415
Gly Ser Tyr Phe Ile Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn Trp
420 425 430
Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His
435 440 445
Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys
450 455 460
<210> 14
<211> 1389
<212> DNA
<213> 家鼷鼠
<400> 14
atgagatgca ggtggatctt tctctttctc ctgtcaggaa ctgcaggtgt cctctctgag 60
gtccagctgc aacagtctgg acctgaactg gtgacgcctg gggcttcagt gaagatatct 120
tgtaaggctt ctggatacac attcactgac cactacatga gctgggtgaa gcagagtcat 180
ggaaaaagcc ttgagtggat tggagatatt aatccctatt ctggtgaaac tacctacaac 240
cagaagttca agggcacggc cacattgact gtagacaagt cttccagtat agcctacatg 300
gagatccgcg gcctgacatc tgaggactct gcagtctatt actgtgcaag agatgattac 360
gacgcctctc cgtttgctta ctggggccaa gggactctgg tcactgtctc tgcagccaaa 420
acgacacccc catctgtcta tccactggcc cctggatctg ctgcccaaac taactccatg 480
gtgaccctgg gatgcctggt caagggctat ttccctgagc cagtgacagt gacctggaac 540
tctggatccc tgtccagcgg tgtgcacacc ttcccagctg tcctgcagtc tgacctctac 600
actctgagca gctcagtgac tgtcccctcc agcacctggc ccagcgagac cgtcacctgc 660
aacgttgccc acccggccag cagcaccaag gtggacaaga aaattgtgcc cagggattgt 720
ggttgtaagc cttgcatatg tacagtccca gaagtatcat ctgtcttcat cttcccccca 780
aagcccaagg atgtgctcac cattactctg actcctaagg tcacgtgtgt tgtggtagac 840
atcagcaagg atgatcccga ggtccagttc agctggtttg tagatgatgt ggaggtgcac 900
acagctcaga cgcaaccccg ggaggagcag ttcaacagca ctttccgctc agtcagtgaa 960
cttcccatca tgcaccagga ctggctcaat ggcaaggagt tcaaatgcag ggtcaacagt 1020
ccagctttcc ctgcccccat cgagaaaacc atctccaaaa ccaaaggcag accgaaggct 1080
ccacaggtgt acaccattcc acctcccaag gagcagatgg ccaaggataa agtcagtctg 1140
acctgcatga taacagactt cttccctgaa gacattactg tggagtggca gtggaatggg 1200
cagccagcgg agaactacaa gaacactcag cccatcatgg acacagatgg ctcttacttc 1260
atctacagca agctcaatgt gcagaagagc aactgggagg caggaaatac tttcacctgc 1320
tctgtgttac atgagggcct gcacaaccac catactgaga agagcctctc ccactctcct 1380
ggtaaatga 1389
<210> 15
<211> 218
<212> PRT
<213> 家鼷鼠
<400> 15
Asp Ile Val Leu Thr Gln Ser Pro Ala Ser Leu Thr Val Ser Leu Gly
1 5 10 15
Leu Arg Ala Thr Ile Ser Cys Lys Ala Ser Gln Ser Val Asp Tyr Asp
20 25 30
Gly Asp Ser Tyr Met Asn Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro
35 40 45
Lys Leu Leu Ile Tyr Ala Ala Ser Asn Leu Glu Ser Gly Ile Pro Ala
50 55 60
Arg Phe Ser Gly Asn Gly Ser Gly Thr Asp Phe Thr Leu Asn Ile His
65 70 75 80
Pro Val Glu Glu Glu Asp Ala Val Thr Tyr Tyr Cys Gln Gln Ser Asn
85 90 95
Glu Asp Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg
100 105 110
Ala Asp Ala Ala Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln
115 120 125
Leu Thr Ser Gly Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr
130 135 140
Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln
145 150 155 160
Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr
165 170 175
Tyr Ser Met Ser Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg
180 185 190
His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro
195 200 205
Ile Val Lys Ser Phe Asn Arg Asn Glu Cys
210 215
<210> 16
<211> 657
<212> DNA
<213> 家鼷鼠
<400> 16
gacattgtgc tgacccaatc tccagcttct ttgactgtgt ctctaggcct gagggccacc 60
atctcctgca aggccagcca aagtgttgat tatgatggtg atagttatat gaactggtac 120
cagcagaaac caggacagcc acccaaactc ctcatctatg ctgcatccaa tctagaatct 180
gggatcccag ccaggtttag tggcaatggg tctgggacag acttcaccct caacatccat 240
cctgtggagg aggaggatgc tgtaacctat tactgtcaac aaagtaatga ggatccgtgg 300
acgttcggtg gaggcaccaa gctggaaatc aaacgggctg atgctgcacc aactgtatcc 360
atcttcccac catccagtga gcagttaaca tctggaggtg cctcagtcgt gtgcttcttg 420
aacaacttct accccaaaga catcaatgtc aagtggaaga ttgatggcag tgaacgacaa 480
aatggcgtcc tgaacagttg gactgatcag gacagcaaag acagcaccta cagcatgagc 540
agcaccctca cgttgaccaa ggacgagtat gaacgacata acagctatac ctgtgaggcc 600
actcacaaga catcaacttc acccattgtc aagagcttca acaggaatga gtgttag 657
<210> 17
<211> 238
<212> PRT
<213> 家鼷鼠
<400> 17
Met Glu Thr Asp Thr Ile Leu Leu Trp Val Leu Leu Leu Trp Val Pro
1 5 10 15
Gly Ser Thr Gly Asp Ile Val Leu Thr Gln Ser Pro Ala Ser Leu Thr
20 25 30
Val Ser Leu Gly Leu Arg Ala Thr Ile Ser Cys Lys Ala Ser Gln Ser
35 40 45
Val Asp Tyr Asp Gly Asp Ser Tyr Met Asn Trp Tyr Gln Gln Lys Pro
50 55 60
Gly Gln Pro Pro Lys Leu Leu Ile Tyr Ala Ala Ser Asn Leu Glu Ser
65 70 75 80
Gly Ile Pro Ala Arg Phe Ser Gly Asn Gly Ser Gly Thr Asp Phe Thr
85 90 95
Leu Asn Ile His Pro Val Glu Glu Glu Asp Ala Val Thr Tyr Tyr Cys
100 105 110
Gln Gln Ser Asn Glu Asp Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu
115 120 125
Glu Ile Lys Arg Ala Asp Ala Ala Pro Thr Val Ser Ile Phe Pro Pro
130 135 140
Ser Ser Glu Gln Leu Thr Ser Gly Gly Ala Ser Val Val Cys Phe Leu
145 150 155 160
Asn Asn Phe Tyr Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly
165 170 175
Ser Glu Arg Gln Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser
180 185 190
Lys Asp Ser Thr Tyr Ser Met Ser Ser Thr Leu Thr Leu Thr Lys Asp
195 200 205
Glu Tyr Glu Arg His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr
210 215 220
Ser Thr Ser Pro Ile Val Lys Ser Phe Asn Arg Asn Glu Cys
225 230 235
<210> 18
<211> 717
<212> DNA
<213> 家鼷鼠
<400> 18
atggagacag acacaatcct gctatgggtg ctgctgctct gggttccagg ctccactggt 60
gacattgtgc tgacccaatc tccagcttct ttgactgtgt ctctaggcct gagggccacc 120
atctcctgca aggccagcca aagtgttgat tatgatggtg atagttatat gaactggtac 180
cagcagaaac caggacagcc acccaaactc ctcatctatg ctgcatccaa tctagaatct 240
gggatcccag ccaggtttag tggcaatggg tctgggacag acttcaccct caacatccat 300
cctgtggagg aggaggatgc tgtaacctat tactgtcaac aaagtaatga ggatccgtgg 360
acgttcggtg gaggcaccaa gctggaaatc aaacgggctg atgctgcacc aactgtatcc 420
atcttcccac catccagtga gcagttaaca tctggaggtg cctcagtcgt gtgcttcttg 480
aacaacttct accccaaaga catcaatgtc aagtggaaga ttgatggcag tgaacgacaa 540
aatggcgtcc tgaacagttg gactgatcag gacagcaaag acagcaccta cagcatgagc 600
agcaccctca cgttgaccaa ggacgagtat gaacgacata acagctatac ctgtgaggcc 660
actcacaaga catcaacttc acccattgtc aagagcttca acaggaatga gtgttag 717
<210> 19
<211> 449
<212> PRT
<213> 家鼷鼠
<400> 19
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Thr
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Cys
20 25 30
Tyr Met Asn Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile
35 40 45
Gly Asp Ile Asn Pro Phe Asn Gly Gly Thr Thr Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Gln Leu Asn Ser Leu Thr Ser Asp Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Ser His Tyr Tyr Phe Asp Gly Arg Val Pro Trp Asp Ala Met
100 105 110
Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr Val Ser Ser Ala Lys Thr
115 120 125
Thr Pro Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr
130 135 140
Asn Ser Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu
145 150 155 160
Pro Val Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His
165 170 175
Thr Phe Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser
180 185 190
Val Thr Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val Thr Cys Asn
195 200 205
Val Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val Pro
210 215 220
Arg Asp Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser
225 230 235 240
Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr
245 250 255
Leu Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp Asp
260 265 270
Pro Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His Thr
275 280 285
Ala Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser
290 295 300
Val Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu
305 310 315 320
Phe Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys
325 330 335
Thr Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr
340 345 350
Ile Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr
355 360 365
Cys Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln
370 375 380
Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met
385 390 395 400
Asp Thr Asp Gly Ser Tyr Phe Ile Tyr Ser Lys Leu Asn Val Gln Lys
405 410 415
Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu
420 425 430
Gly Leu His Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro Gly
435 440 445
Lys
<210> 20
<211> 1350
<212> DNA
<213> 家鼷鼠
<400> 20
gaggtccagc tgcaacaatc tggacctgag ctggtgaagc ctgggacttc agtgaagatg 60
tcctgtaagg cttctggata cacattcact gactgctaca tgaactgggt gaagcagagc 120
catgggaaga gccttgaatg gattggagat attaatcctt tcaacggtgg tactacctac 180
aaccagaagt tcaagggcaa ggccacattg actgtagaca aatcctccag cacagcctac 240
atgcagctca acagcctgac atctgacgac tctgcagtct attactgtgc aagatcccat 300
tattacttcg atggtagagt cccttgggat gctatggact actggggtca aggaacctca 360
gtcaccgtct cctcagccaa aacgacaccc ccatctgtct atccactggc ccctggatct 420
gctgcccaaa ctaactccat ggtgaccctg ggatgcctgg tcaagggcta tttccctgag 480
ccagtgacag tgacctggaa ctctggatcc ctgtccagcg gtgtgcacac cttcccagct 540
gtcctgcagt ctgacctcta cactctgagc agctcagtga ctgtcccctc cagcacctgg 600
cccagcgaga ccgtcacctg caacgttgcc cacccggcca gcagcaccaa ggtggacaag 660
aaaattgtgc ccagggattg tggttgtaag ccttgcatat gtacagtccc agaagtatca 720
tctgtcttca tcttcccccc aaagcccaag gatgtgctca ccattactct gactcctaag 780
gtcacgtgtg ttgtggtaga catcagcaag gatgatcccg aggtccagtt cagctggttt 840
gtagatgatg tggaggtgca cacagctcag acgcaacccc gggaggagca gttcaacagc 900
actttccgct cagtcagtga acttcccatc atgcaccagg actggctcaa tggcaaggag 960
ttcaaatgca gggtcaacag tgcagctttc cctgccccca tcgagaaaac catctccaaa 1020
accaaaggca gaccgaaggc tccacaggtg tacaccattc cacctcccaa ggagcagatg 1080
gccaaggata aagtcagtct gacctgcatg ataacagact tcttccctga agacattact 1140
gtggagtggc agtggaatgg gcagccagcg gagaactaca agaacactca gcccatcatg 1200
gacacagatg gctcttactt catctacagc aagctcaatg tgcagaagag caactgggag 1260
gcaggaaata ctttcacctg ctctgtgtta catgagggcc tgcacaacca ccatactgag 1320
aagagcctct cccactctcc tggtaaatga 1350
<210> 21
<211> 468
<212> PRT
<213> 家鼷鼠
<400> 21
Met Gly Trp Asn Trp Ile Phe Leu Phe Leu Leu Ser Gly Thr Ala Gly
1 5 10 15
Val Tyr Ser Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys
20 25 30
Pro Gly Thr Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe
35 40 45
Thr Asp Cys Tyr Met Asn Trp Val Lys Gln Ser His Gly Lys Ser Leu
50 55 60
Glu Trp Ile Gly Asp Ile Asn Pro Phe Asn Gly Gly Thr Thr 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 Gln Leu Asn Ser Leu Thr Ser Asp Asp Ser Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Ser His Tyr Tyr Phe Asp Gly Arg Val Pro Trp
115 120 125
Asp Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr Val Ser Ser
130 135 140
Ala Lys Thr Thr Pro Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala
145 150 155 160
Ala Gln Thr Asn Ser Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr
165 170 175
Phe Pro Glu Pro Val Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser
180 185 190
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu
195 200 205
Ser Ser Ser Val Thr Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val
210 215 220
Thr Cys Asn Val Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys
225 230 235 240
Ile Val Pro Arg Asp Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro
245 250 255
Glu Val Ser Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu
260 265 270
Thr Ile Thr Leu Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser
275 280 285
Lys Asp Asp Pro Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu
290 295 300
Val His Thr Ala Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr
305 310 315 320
Phe Arg Ser Val Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn
325 330 335
Gly Lys Glu Phe Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro
340 345 350
Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln
355 360 365
Val Tyr Thr Ile Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val
370 375 380
Ser Leu Thr Cys Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val
385 390 395 400
Glu Trp Gln Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln
405 410 415
Pro Ile Met Asp Thr Asp Gly Ser Tyr Phe Ile Tyr Ser Lys Leu Asn
420 425 430
Val Gln Lys Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val
435 440 445
Leu His Glu Gly Leu His Asn His His Thr Glu Lys Ser Leu Ser His
450 455 460
Ser Pro Gly Lys
465
<210> 22
<211> 1407
<212> DNA
<213> 家鼷鼠
<400> 22
atgggatgga actggatctt tctcttcctc ttgtcaggaa ctgcaggtgt ctactctgag 60
gtccagctgc aacaatctgg acctgagctg gtgaagcctg ggacttcagt gaagatgtcc 120
tgtaaggctt ctggatacac attcactgac tgctacatga actgggtgaa gcagagccat 180
gggaagagcc ttgaatggat tggagatatt aatcctttca acggtggtac tacctacaac 240
cagaagttca agggcaaggc cacattgact gtagacaaat cctccagcac agcctacatg 300
cagctcaaca gcctgacatc tgacgactct gcagtctatt actgtgcaag atcccattat 360
tacttcgatg gtagagtccc ttgggatgct atggactact ggggtcaagg aacctcagtc 420
accgtctcct cagccaaaac gacaccccca tctgtctatc cactggcccc tggatctgct 480
gcccaaacta actccatggt gaccctggga tgcctggtca agggctattt ccctgagcca 540
gtgacagtga cctggaactc tggatccctg tccagcggtg tgcacacctt cccagctgtc 600
ctgcagtctg acctctacac tctgagcagc tcagtgactg tcccctccag cacctggccc 660
agcgagaccg tcacctgcaa cgttgcccac ccggccagca gcaccaaggt ggacaagaaa 720
attgtgccca gggattgtgg ttgtaagcct tgcatatgta cagtcccaga agtatcatct 780
gtcttcatct tccccccaaa gcccaaggat gtgctcacca ttactctgac tcctaaggtc 840
acgtgtgttg tggtagacat cagcaaggat gatcccgagg tccagttcag ctggtttgta 900
gatgatgtgg aggtgcacac agctcagacg caaccccggg aggagcagtt caacagcact 960
ttccgctcag tcagtgaact tcccatcatg caccaggact ggctcaatgg caaggagttc 1020
aaatgcaggg tcaacagtgc agctttccct gcccccatcg agaaaaccat ctccaaaacc 1080
aaaggcagac cgaaggctcc acaggtgtac accattccac ctcccaagga gcagatggcc 1140
aaggataaag tcagtctgac ctgcatgata acagacttct tccctgaaga cattactgtg 1200
gagtggcagt ggaatgggca gccagcggag aactacaaga acactcagcc catcatggac 1260
acagatggct cttacttcat ctacagcaag ctcaatgtgc agaagagcaa ctgggaggca 1320
ggaaatactt tcacctgctc tgtgttacat gagggcctgc acaaccacca tactgagaag 1380
agcctctccc actctcctgg taaatga 1407
<210> 23
<211> 217
<212> PRT
<213> 人工序列
<220>
<223> 合成多肽
<220>
<221> MISC_FEATURE
<223> 兔-小鼠嵌合体
<400> 23
Ala Gln Val Leu Thr Gln Thr Pro Ala Ser Val Ser Ala Ala Val Gly
1 5 10 15
Gly Thr Val Thr Ile Asn Cys Gln Ser Ser Gln Ser Val Tyr Asp Asn
20 25 30
Asn Trp Leu Ala Trp Phe Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu
35 40 45
Leu Ile Tyr Asp Ala Ser Asp Leu Ala Ser Gly Val Pro Ser Arg Phe
50 55 60
Ser Gly Ser Gly Ser Gly Thr Gln Phe Thr Leu Thr Ile Ser Gly Val
65 70 75 80
Gln Cys Ala Asp Ala Ala Thr Tyr Tyr Cys Gln Gly Ala Tyr Asn Asp
85 90 95
Val Ile Tyr Ala Phe Gly Gly Gly Thr Glu Val Val Val Lys Arg Thr
100 105 110
Asp Ala Ala Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln Leu
115 120 125
Thr Ser Gly Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr Pro
130 135 140
Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln Asn
145 150 155 160
Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr Tyr
165 170 175
Ser Met Ser Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg His
180 185 190
Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro Ile
195 200 205
Val Lys Ser Phe Asn Arg Asn Glu Cys
210 215
<210> 24
<211> 654
<212> DNA
<213> 人工序列
<220>
<223> 合成多核苷酸
<220>
<221> misc_feature
<223> 兔-小鼠嵌合体
<400> 24
gcgcaagtgc tgacccagac tccagcctcc gtgtctgcag ctgtgggagg cacagtcacc 60
atcaattgcc agtccagtca gagtgtttat gataacaact ggttagcctg gtttcagcag 120
aaaccagggc agcctcccaa gctcctgatt tatgatgcat ccgatctggc atctggggtc 180
ccatcgcggt tcagtggcag tggatctggg acacagttca ctctcaccat cagcggcgtg 240
cagtgtgccg atgctgccac ttactactgt caaggcgctt ataatgatgt tatttatgct 300
ttcggcggag ggaccgaggt ggtggtcaaa cgtacggatg ctgcaccaac tgtatccatc 360
ttcccaccat ccagtgagca gttaacatct ggaggtgcct cagtcgtgtg cttcttgaac 420
aacttctacc ccaaagacat caatgtcaag tggaagattg atggcagtga acgacaaaat 480
ggcgtcctga acagttggac tgatcaggac agcaaagaca gcacctacag catgagcagc 540
accctcacgt tgaccaagga cgagtatgaa cgacataaca gctatacctg tgaggccact 600
cacaagacat caacttcacc cattgtcaag agcttcaaca ggaatgagtg ttag 654
<210> 25
<211> 239
<212> PRT
<213> 人工序列
<220>
<223> 合成多肽
<220>
<221> MISC_FEATURE
<223> 兔-小鼠嵌合体
<400> 25
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Thr Phe Ala Gln Val Leu Thr Gln Thr Pro Ala Ser
20 25 30
Val Ser Ala Ala Val Gly Gly Thr Val Thr Ile Asn Cys Gln Ser Ser
35 40 45
Gln Ser Val Tyr Asp Asn Asn Trp Leu Ala Trp Phe Gln Gln Lys Pro
50 55 60
Gly Gln Pro Pro Lys Leu Leu Ile Tyr Asp Ala Ser Asp Leu Ala Ser
65 70 75 80
Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Gln Phe Thr
85 90 95
Leu Thr Ile Ser Gly Val Gln Cys Ala Asp Ala Ala Thr Tyr Tyr Cys
100 105 110
Gln Gly Ala Tyr Asn Asp Val Ile Tyr Ala Phe Gly Gly Gly Thr Glu
115 120 125
Val Val Val Lys Arg Thr Asp Ala Ala Pro Thr Val Ser Ile Phe Pro
130 135 140
Pro Ser Ser Glu Gln Leu Thr Ser Gly Gly Ala Ser Val Val Cys Phe
145 150 155 160
Leu Asn Asn Phe Tyr Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp
165 170 175
Gly Ser Glu Arg Gln Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp
180 185 190
Ser Lys Asp Ser Thr Tyr Ser Met Ser Ser Thr Leu Thr Leu Thr Lys
195 200 205
Asp Glu Tyr Glu Arg His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys
210 215 220
Thr Ser Thr Ser Pro Ile Val Lys Ser Phe Asn Arg Asn Glu Cys
225 230 235
<210> 26
<211> 720
<212> DNA
<213> 人工序列
<220>
<223> 合成多核苷酸
<220>
<221> misc_feature
<223> 兔-小鼠嵌合体
<400> 26
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
acatttgcgc aagtgctgac ccagactcca gcctccgtgt ctgcagctgt gggaggcaca 120
gtcaccatca attgccagtc cagtcagagt gtttatgata acaactggtt agcctggttt 180
cagcagaaac cagggcagcc tcccaagctc ctgatttatg atgcatccga tctggcatct 240
ggggtcccat cgcggttcag tggcagtgga tctgggacac agttcactct caccatcagc 300
ggcgtgcagt gtgccgatgc tgccacttac tactgtcaag gcgcttataa tgatgttatt 360
tatgctttcg gcggagggac cgaggtggtg gtcaaacgta cggatgctgc accaactgta 420
tccatcttcc caccatccag tgagcagtta acatctggag gtgcctcagt cgtgtgcttc 480
ttgaacaact tctaccccaa agacatcaat gtcaagtgga agattgatgg cagtgaacga 540
caaaatggcg tcctgaacag ttggactgat caggacagca aagacagcac ctacagcatg 600
agcagcaccc tcacgttgac caaggacgag tatgaacgac ataacagcta tacctgtgag 660
gccactcaca agacatcaac ttcacccatt gtcaagagct tcaacaggaa tgagtgttag 720
<210> 27
<211> 433
<212> PRT
<213> 人工序列
<220>
<223> 合成多肽
<220>
<221> MISC_FEATURE
<223> 人源化抗体
<400> 27
Gln Ser Leu Glu Glu Ser Gly Gly Arg Leu Val Thr Pro Gly Thr Pro
1 5 10 15
Leu Thr Leu Thr Cys Thr Ala Ser Gly Phe Ser Leu Ser Ser Tyr Trp
20 25 30
Met Asn Trp Val Arg Gln Ala Pro Gly Glu Gly Leu Glu Trp Ile Gly
35 40 45
Thr Ile Asp Ser Gly Gly Arg Thr Asp Tyr Ala Ser Trp Ala Lys Gly
50 55 60
Arg Phe Thr Ile Ser Arg Thr Ser Thr Thr Met Asp Leu Lys Met Thr
65 70 75 80
Ser Leu Thr Thr Gly Asp Thr Ala Arg Tyr Phe Cys Ala Arg Asn Trp
85 90 95
Asn Leu Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr
100 105 110
Lys Gly Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr
115 120 125
Asn Ser Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu
130 135 140
Pro Val Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His
145 150 155 160
Thr Phe Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser
165 170 175
Val Thr Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val Thr Cys Asn
180 185 190
Val Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val Pro
195 200 205
Arg Asp Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser
210 215 220
Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr
225 230 235 240
Leu Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp Asp
245 250 255
Pro Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His Thr
260 265 270
Ala Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser
275 280 285
Val Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu
290 295 300
Phe Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys
305 310 315 320
Thr Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr
325 330 335
Ile Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr
340 345 350
Cys Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln
355 360 365
Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met
370 375 380
Asn Thr Asn Gly Ser Tyr Phe Val Tyr Ser Lys Leu Asn Val Gln Lys
385 390 395 400
Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu
405 410 415
Gly Leu His Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro Gly
420 425 430
Lys
<210> 28
<211> 1302
<212> DNA
<213> 人工序列
<220>
<223> 合成多核苷酸
<220>
<221> misc_feature
<223> 人源化抗体
<400> 28
cagtcgctgg aggagtccgg gggtcgcctg gtcacgcctg ggacacccct gacactcacc 60
tgcacagcct ctggattctc cctcagtagt tattggatga actgggtccg ccaggctcca 120
ggggaggggc tggaatggat cggaaccatt gattctggtg gtaggacgga ctacgcgagc 180
tgggcaaaag gccgattcac catctccaga acctcgacta cgatggatct gaaaatgacc 240
agtctgacga ccggggacac ggcccgttat ttctgtgcca gaaattggaa cttgtggggc 300
caaggcaccc tcgtcaccgt ctcgagcgct tctacaaagg gcccatctgt ctatccactg 360
gcccctggat ctgctgccca aactaactcc atggtgaccc tgggatgcct ggtcaagggc 420
tatttccctg agccagtgac agtgacctgg aactctggat ccctgtccag cggtgtgcac 480
accttcccag ctgtcctgca gtctgacctc tacactctga gcagctcagt gactgtcccc 540
tccagcacct ggcccagcga gaccgtcacc tgcaacgttg cccacccggc cagcagcacc 600
aaggtggaca agaaaattgt gcccagggat tgtggttgta agccttgcat atgtacagtc 660
ccagaagtat catctgtctt catcttcccc ccaaagccca aggatgtgct caccattact 720
ctgactccta aggtcacgtg tgttgtggta gacatcagca aggatgatcc cgaggtccag 780
ttcagctggt ttgtagatga tgtggaggtg cacacagctc agacgcaacc ccgggaggag 840
cagttcaaca gcactttccg ctcagtcagt gaacttccca tcatgcacca ggactggctc 900
aatggcaagg agttcaaatg cagggtcaac agtgcagctt tccctgcccc catcgagaaa 960
accatctcca aaaccaaagg cagaccgaag gctccacagg tgtacaccat tccacctccc 1020
aaggagcaga tggccaagga taaagtcagt ctgacctgca tgataacaga cttcttccct 1080
gaagacatta ctgtggagtg gcagtggaat gggcagccag cggagaacta caagaacact 1140
cagcccatca tggacacaga tggctcttac ttcgtctaca gcaagctcaa tgtgcagaag 1200
agcaactggg aggcaggaaa tactttcacc tgctctgtgt tacatgaggg cctgcacaac 1260
caccatactg agaagagcct ctcccactct cctggtaaat ga 1302
<210> 29
<211> 452
<212> PRT
<213> 人工序列
<220>
<223> 合成多肽
<220>
<221> MISC_FEATURE
<223> 人源化抗体
<400> 29
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val His Cys Gln Ser Leu Glu Glu Ser Gly Gly Arg Leu Val Thr Pro
20 25 30
Gly Thr Pro Leu Thr Leu Thr Cys Thr Ala Ser Gly Phe Ser Leu Ser
35 40 45
Ser Tyr Trp Met Asn Trp Val Arg Gln Ala Pro Gly Glu Gly Leu Glu
50 55 60
Trp Ile Gly Thr Ile Asp Ser Gly Gly Arg Thr Asp Tyr Ala Ser Trp
65 70 75 80
Ala Lys Gly Arg Phe Thr Ile Ser Arg Thr Ser Thr Thr Met Asp Leu
85 90 95
Lys Met Thr Ser Leu Thr Thr Gly Asp Thr Ala Arg Tyr Phe Cys Ala
100 105 110
Arg Asn Trp Asn Leu Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120 125
Ala Ser Thr Lys Gly Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala
130 135 140
Ala Gln Thr Asn Ser Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr
145 150 155 160
Phe Pro Glu Pro Val Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser
165 170 175
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu
180 185 190
Ser Ser Ser Val Thr Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val
195 200 205
Thr Cys Asn Val Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys
210 215 220
Ile Val Pro Arg Asp Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro
225 230 235 240
Glu Val Ser Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu
245 250 255
Thr Ile Thr Leu Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser
260 265 270
Lys Asp Asp Pro Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu
275 280 285
Val His Thr Ala Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr
290 295 300
Phe Arg Ser Val Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn
305 310 315 320
Gly Lys Glu Phe Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro
325 330 335
Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln
340 345 350
Val Tyr Thr Ile Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val
355 360 365
Ser Leu Thr Cys Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val
370 375 380
Glu Trp Gln Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln
385 390 395 400
Pro Ile Met Asn Thr Asn Gly Ser Tyr Phe Val Tyr Ser Lys Leu Asn
405 410 415
Val Gln Lys Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val
420 425 430
Leu His Glu Gly Leu His Asn His His Thr Glu Lys Ser Leu Ser His
435 440 445
Ser Pro Gly Lys
450
<210> 30
<211> 1359
<212> DNA
<213> 人工序列
<220>
<223> 合成多核苷酸
<220>
<221> misc_feature
<223> 人源化抗体
<400> 30
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccactgtcag 60
tcgctggagg agtccggggg tcgcctggtc acgcctggga cacccctgac actcacctgc 120
acagcctctg gattctccct cagtagttat tggatgaact gggtccgcca ggctccaggg 180
gaggggctgg aatggatcgg aaccattgat tctggtggta ggacggacta cgcgagctgg 240
gcaaaaggcc gattcaccat ctccagaacc tcgactacga tggatctgaa aatgaccagt 300
ctgacgaccg gggacacggc ccgttatttc tgtgccagaa attggaactt gtggggccaa 360
ggcaccctcg tcaccgtctc gagcgcttct acaaagggcc catctgtcta tccactggcc 420
cctggatctg ctgcccaaac taactccatg gtgaccctgg gatgcctggt caagggctat 480
ttccctgagc cagtgacagt gacctggaac tctggatccc tgtccagcgg tgtgcacacc 540
ttcccagctg tcctgcagtc tgacctctac actctgagca gctcagtgac tgtcccctcc 600
agcacctggc ccagcgagac cgtcacctgc aacgttgccc acccggccag cagcaccaag 660
gtggacaaga aaattgtgcc cagggattgt ggttgtaagc cttgcatatg tacagtccca 720
gaagtatcat ctgtcttcat cttcccccca aagcccaagg atgtgctcac cattactctg 780
actcctaagg tcacgtgtgt tgtggtagac atcagcaagg atgatcccga ggtccagttc 840
agctggtttg tagatgatgt ggaggtgcac acagctcaga cgcaaccccg ggaggagcag 900
ttcaacagca ctttccgctc agtcagtgaa cttcccatca tgcaccagga ctggctcaat 960
ggcaaggagt tcaaatgcag ggtcaacagt gcagctttcc ctgcccccat cgagaaaacc 1020
atctccaaaa ccaaaggcag accgaaggct ccacaggtgt acaccattcc acctcccaag 1080
gagcagatgg ccaaggataa agtcagtctg acctgcatga taacagactt cttccctgaa 1140
gacattactg tggagtggca gtggaatggg cagccagcgg agaactacaa gaacactcag 1200
cccatcatgg acacagatgg ctcttacttc gtctacagca agctcaatgt gcagaagagc 1260
aactgggagg caggaaatac tttcacctgc tctgtgttac atgagggcct gcacaaccac 1320
catactgaga agagcctctc ccactctcct ggtaaatga 1359
<210> 31
<211> 213
<212> PRT
<213> 家鼷鼠
<400> 31
Gln Ile Val Leu Thr Gln Ser Pro Thr Ile Val Ser Ala Ser Pro Gly
1 5 10 15
Glu Lys Val Thr Leu Ile Cys Ser Ala Ser Ser Ser Val Ser Phe Val
20 25 30
Asp Trp Phe Gln Gln Lys Pro Gly Thr Ser Pro Lys Arg Trp Ile Tyr
35 40 45
Arg Thr Ser Asn Leu Gly Phe Gly Val Pro Ala Arg Phe Ser Gly Gly
50 55 60
Gly Ser Gly Thr Ser His Ser Leu Thr Ile Ser Arg Met Glu Ala Glu
65 70 75 80
Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Arg Ser Thr Tyr Pro Pro Thr
85 90 95
Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys Arg Ala Asp Ala Ala Pro
100 105 110
Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln Leu Thr Ser Gly Gly
115 120 125
Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr Pro Lys Asp Ile Asn
130 135 140
Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln Asn Gly Val Leu Asn
145 150 155 160
Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr Tyr Ser Met Ser Ser
165 170 175
Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg His Asn Ser Tyr Thr
180 185 190
Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro Ile Val Lys Ser Phe
195 200 205
Asn Arg Asn Glu Cys
210
<210> 32
<211> 642
<212> DNA
<213> 家鼷鼠
<400> 32
caaattgttc tcacccagtc tccaacaatc gtgtctgcat ctccagggga gaaggtcacc 60
ctaatctgca gtgccagttc aagtgtaagt ttcgtggact ggttccagca gaagccaggc 120
acttctccca aacgctggat ttacagaaca tccaacctgg gttttggagt ccctgctcgc 180
ttcagtggcg gtggatctgg gacctctcac tctctcacaa tcagccgaat ggaggctgaa 240
gatgctgcca cttattactg ccagcaaagg agtacttacc cacccacgtt cggtgctggg 300
accaagctgg aactgaaacg ggctgatgct gcaccaactg tatccatctt cccaccatcc 360
agtgagcagt taacatctgg aggtgcctca gtcgtgtgct tcttgaacaa cttctacccc 420
aaagacatca atgtcaagtg gaagattgat ggcagtgaac gacaaaatgg cgtcctgaac 480
agttggactg atcaggacag caaagacagc acctacagca tgagcagcac cctcacgttg 540
accaaggacg agtatgaacg acataacagc tatacctgtg aggccactca caagacatca 600
acttcaccca ttgtcaagag cttcaacagg aatgagtgtt ag 642
<210> 33
<211> 235
<212> PRT
<213> 家鼷鼠
<400> 33
Met His Phe Gln Val Gln Ile Phe Ser Phe Leu Leu Ile Ser Ala Ser
1 5 10 15
Val Ile Val Ser Arg Gly Gln Ile Val Leu Thr Gln Ser Pro Thr Ile
20 25 30
Val Ser Ala Ser Pro Gly Glu Lys Val Thr Leu Ile Cys Ser Ala Ser
35 40 45
Ser Ser Val Ser Phe Val Asp Trp Phe Gln Gln Lys Pro Gly Thr Ser
50 55 60
Pro Lys Arg Trp Ile Tyr Arg Thr Ser Asn Leu Gly Phe Gly Val Pro
65 70 75 80
Ala Arg Phe Ser Gly Gly Gly Ser Gly Thr Ser His Ser Leu Thr Ile
85 90 95
Ser Arg Met Glu Ala Glu Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Arg
100 105 110
Ser Thr Tyr Pro Pro Thr Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys
115 120 125
Arg Ala Asp Ala Ala Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu
130 135 140
Gln Leu Thr Ser Gly Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe
145 150 155 160
Tyr Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg
165 170 175
Gln Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser
180 185 190
Thr Tyr Ser Met Ser Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu
195 200 205
Arg His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser
210 215 220
Pro Ile Val Lys Ser Phe Asn Arg Asn Glu Cys
225 230 235
<210> 34
<211> 708
<212> DNA
<213> 家鼷鼠
<400> 34
atgcattttc aagtgcagat tttcagcttc ctgctaatca gtgcctcagt catagtgtcc 60
agagggcaaa ttgttctcac ccagtctcca acaatcgtgt ctgcatctcc aggggagaag 120
gtcaccctaa tctgcagtgc cagttcaagt gtaagtttcg tggactggtt ccagcagaag 180
ccaggcactt ctcccaaacg ctggatttac agaacatcca acctgggttt tggagtccct 240
gctcgcttca gtggcggtgg atctgggacc tctcactctc tcacaatcag ccgaatggag 300
gctgaagatg ctgccactta ttactgccag caaaggagta cttacccacc cacgttcggt 360
gctgggacca agctggaact gaaacgggct gatgctgcac caactgtatc catcttccca 420
ccatccagtg agcagttaac atctggaggt gcctcagtcg tgtgcttctt gaacaacttc 480
taccccaaag acatcaatgt caagtggaag attgatggca gtgaacgaca aaatggcgtc 540
ctgaacagtt ggactgatca ggacagcaaa gacagcacct acagcatgag cagcaccctc 600
acgttgacca aggacgagta tgaacgacat aacagctata cctgtgaggc cactcacaag 660
acatcaactt cacccattgt caagagcttc aacaggaatg agtgttag 708
<210> 35
<211> 449
<212> PRT
<213> 家鼷鼠
<400> 35
Gln Val Thr Leu Lys Glu Ser Gly Pro Gly Ile Leu Gln Pro Ser Gln
1 5 10 15
Thr Leu Ser Leu Thr Cys Ser Phe Ser Gly Phe Ser Leu Ser Thr Ser
20 25 30
Gly Met Gly Val Gly Trp Ile Arg His Pro Ser Gly Lys Asn Leu Glu
35 40 45
Trp Leu Ala His Ile Trp Trp Asp Asp Val Lys Arg Tyr Asn Pro Val
50 55 60
Leu Lys Ser Arg Leu Thr Ile Ser Lys Asp Thr Ser Asn Ser Gln Val
65 70 75 80
Phe Leu Lys Ile Ala Asn Val Asp Thr Ala Asp Thr Ala Thr Tyr Tyr
85 90 95
Cys Ala Arg Ile Glu Asp Phe Asp Tyr Asp Glu Glu Tyr Tyr Ala Met
100 105 110
Asp Tyr Trp Gly Gln Gly Thr Ser Val Ile Val Ser Ser Ala Lys Thr
115 120 125
Thr Pro Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr
130 135 140
Asn Ser Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu
145 150 155 160
Pro Val Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His
165 170 175
Thr Phe Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser
180 185 190
Val Thr Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val Thr Cys Asn
195 200 205
Val Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val Pro
210 215 220
Arg Asp Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser
225 230 235 240
Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr
245 250 255
Leu Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp Asp
260 265 270
Pro Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His Thr
275 280 285
Ala Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser
290 295 300
Val Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu
305 310 315 320
Phe Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys
325 330 335
Thr Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr
340 345 350
Ile Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr
355 360 365
Cys Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln
370 375 380
Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met
385 390 395 400
Asp Thr Asp Gly Ser Tyr Phe Val Tyr Ser Lys Leu Asn Val Gln Lys
405 410 415
Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu
420 425 430
Gly Leu His Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro Gly
435 440 445
Lys
<210> 36
<211> 1350
<212> DNA
<213> 家鼷鼠
<400> 36
caggttactc tgaaagagtc tggccctggg atattgcagc cctcccagac cctcagtctg 60
acttgttctt tctctgggtt ttcactgagc acttctggta tgggtgtagg ctggattcgt 120
cacccatcag ggaagaatct ggagtggctg gcacacattt ggtgggatga tgtcaagcgc 180
tataacccag tcctgaagag ccgactgact atctccaagg atacctccaa cagccaggta 240
ttcctcaaga tcgccaatgt ggacactgca gatactgcca catactactg tgctcgaata 300
gaggactttg attacgacga ggagtattat gctatggact actggggtca aggaacctca 360
gtcatcgtct cctcagccaa aacgacaccc ccatctgtct atccactggc ccctggatct 420
gctgcccaaa ctaactccat ggtgaccctg ggatgcctgg tcaagggcta tttccctgag 480
ccagtgacag tgacctggaa ctctggatcc ctgtccagcg gtgtgcacac cttcccagct 540
gtcctgcagt ctgacctcta cactctgagc agctcagtga ctgtcccctc cagcacctgg 600
cccagcgaga ccgtcacctg caacgttgcc cacccggcca gcagcaccaa ggtggacaag 660
aaaattgtgc ccagggattg tggttgtaag ccttgcatat gtacagtccc agaagtatca 720
tctgtcttca tcttcccccc aaagcccaag gatgtgctca ccattactct gactcctaag 780
gtcacgtgtg ttgtggtaga catcagcaag gatgatcccg aggtccagtt cagctggttt 840
gtagatgatg tggaggtgca cacagctcag acgcaacccc gggaggagca gttcaacagc 900
actttccgct cagtcagtga acttcccatc atgcaccagg actggctcaa tggcaaggag 960
ttcaaatgca gggtcaacag tgcagctttc cctgccccca tcgagaaaac catctccaaa 1020
accaaaggca gaccgaaggc tccacaggtg tacaccattc cacctcccaa ggagcagatg 1080
gccaaggata aagtcagtct gacctgcatg ataacagact tcttccctga agacattact 1140
gtggagtggc agtggaatgg gcagccagcg gagaactaca agaacactca gcccatcatg 1200
gacacagatg gctcttactt cgtctacagc aagctcaatg tgcagaagag caactgggag 1260
gcaggaaata ctttcacctg ctctgtgtta catgagggcc tgcacaacca ccatactgag 1320
aagagcctct cccactctcc tggtaaatga 1350
<210> 37
<211> 468
<212> PRT
<213> 家鼷鼠
<400> 37
Met Gly Arg Leu Thr Ser Ser Phe Leu Leu Leu Ile Val Pro Ala Tyr
1 5 10 15
Val Leu Ser Gln Val Thr Leu Lys Glu Ser Gly Pro Gly Ile Leu Gln
20 25 30
Pro Ser Gln Thr Leu Ser Leu Thr Cys Ser Phe Ser Gly Phe Ser Leu
35 40 45
Ser Thr Ser Gly Met Gly Val Gly Trp Ile Arg His Pro Ser Gly Lys
50 55 60
Asn Leu Glu Trp Leu Ala His Ile Trp Trp Asp Asp Val Lys Arg Tyr
65 70 75 80
Asn Pro Val Leu Lys Ser Arg Leu Thr Ile Ser Lys Asp Thr Ser Asn
85 90 95
Ser Gln Val Phe Leu Lys Ile Ala Asn Val Asp Thr Ala Asp Thr Ala
100 105 110
Thr Tyr Tyr Cys Ala Arg Ile Glu Asp Phe Asp Tyr Asp Glu Glu Tyr
115 120 125
Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser Val Ile Val Ser Ser
130 135 140
Ala Lys Thr Thr Pro Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala
145 150 155 160
Ala Gln Thr Asn Ser Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr
165 170 175
Phe Pro Glu Pro Val Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser
180 185 190
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu
195 200 205
Ser Ser Ser Val Thr Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val
210 215 220
Thr Cys Asn Val Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys
225 230 235 240
Ile Val Pro Arg Asp Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro
245 250 255
Glu Val Ser Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu
260 265 270
Thr Ile Thr Leu Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser
275 280 285
Lys Asp Asp Pro Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu
290 295 300
Val His Thr Ala Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr
305 310 315 320
Phe Arg Ser Val Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn
325 330 335
Gly Lys Glu Phe Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro
340 345 350
Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln
355 360 365
Val Tyr Thr Ile Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val
370 375 380
Ser Leu Thr Cys Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val
385 390 395 400
Glu Trp Gln Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln
405 410 415
Pro Ile Met Asp Thr Asp Gly Ser Tyr Phe Val Tyr Ser Lys Leu Asn
420 425 430
Val Gln Lys Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val
435 440 445
Leu His Glu Gly Leu His Asn His His Thr Glu Lys Ser Leu Ser His
450 455 460
Ser Pro Gly Lys
465
<210> 38
<211> 1407
<212> DNA
<213> 家鼷鼠
<400> 38
atgggcaggc ttacttcttc attcctgcta ctgattgtcc ctgcatatgt cctgtcccag 60
gttactctga aagagtctgg ccctgggata ttgcagccct cccagaccct cagtctgact 120
tgttctttct ctgggttttc actgagcact tctggtatgg gtgtaggctg gattcgtcac 180
ccatcaggga agaatctgga gtggctggca cacatttggt gggatgatgt caagcgctat 240
aacccagtcc tgaagagccg actgactatc tccaaggata cctccaacag ccaggtattc 300
ctcaagatcg ccaatgtgga cactgcagat actgccacat actactgtgc tcgaatagag 360
gactttgatt acgacgagga gtattatgct atggactact ggggtcaagg aacctcagtc 420
atcgtctcct cagccaaaac gacaccccca tctgtctatc cactggcccc tggatctgct 480
gcccaaacta actccatggt gaccctggga tgcctggtca agggctattt ccctgagcca 540
gtgacagtga cctggaactc tggatccctg tccagcggtg tgcacacctt cccagctgtc 600
ctgcagtctg acctctacac tctgagcagc tcagtgactg tcccctccag cacctggccc 660
agcgagaccg tcacctgcaa cgttgcccac ccggccagca gcaccaaggt ggacaagaaa 720
attgtgccca gggattgtgg ttgtaagcct tgcatatgta cagtcccaga agtatcatct 780
gtcttcatct tccccccaaa gcccaaggat gtgctcacca ttactctgac tcctaaggtc 840
acgtgtgttg tggtagacat cagcaaggat gatcccgagg tccagttcag ctggtttgta 900
gatgatgtgg aggtgcacac agctcagacg caaccccggg aggagcagtt caacagcact 960
ttccgctcag tcagtgaact tcccatcatg caccaggact ggctcaatgg caaggagttc 1020
aaatgcaggg tcaacagtgc agctttccct gcccccatcg agaaaaccat ctccaaaacc 1080
aaaggcagac cgaaggctcc acaggtgtac accattccac ctcccaagga gcagatggcc 1140
aaggataaag tcagtctgac ctgcatgata acagacttct tccctgaaga cattactgtg 1200
gagtggcagt ggaatgggca gccagcggag aactacaaga acactcagcc catcatggac 1260
acagatggct cttacttcgt ctacagcaag ctcaatgtgc agaagagcaa ctgggaggca 1320
ggaaatactt tcacctgctc tgtgttacat gagggcctgc acaaccacca tactgagaag 1380
agcctctccc actctcctgg taaatga 1407
<210> 39
<211> 5
<212> PRT
<213> 家鼷鼠
<400> 39
Asp His Tyr Met Ser
1 5
<210> 40
<211> 17
<212> PRT
<213> 家鼷鼠
<400> 40
Asp Ile Asn Pro Tyr Ser Gly Glu Thr Thr Tyr Asn Gln Lys Phe Lys
1 5 10 15
Gly
<210> 41
<211> 10
<212> PRT
<213> 家鼷鼠
<400> 41
Asp Asp Tyr Asp Ala Ser Pro Phe Ala Tyr
1 5 10
<210> 42
<211> 11
<212> PRT
<213> 家鼷鼠
<400> 42
Gln Ala Ser Gln Gly Thr Ser Ile Asn Leu Asn
1 5 10
<210> 43
<211> 7
<212> PRT
<213> 家鼷鼠
<400> 43
Gly Ser Ser Asn Leu Glu Asp
1 5
<210> 44
<211> 9
<212> PRT
<213> 家鼷鼠
<400> 44
Leu Gln His Ser Tyr Leu Pro Tyr Thr
1 5
<210> 45
<211> 5
<212> PRT
<213> 家鼷鼠
<400> 45
Asp Cys Tyr Met Asn
1 5
<210> 46
<211> 17
<212> PRT
<213> 家鼷鼠
<400> 46
Asp Ile Asn Pro Phe Asn Gly Gly Thr Thr Tyr Asn Gln Lys Phe Lys
1 5 10 15
Gly
<210> 47
<211> 16
<212> PRT
<213> 家鼷鼠
<400> 47
Ser His Tyr Tyr Phe Asp Gly Arg Val Pro Trp Asp Ala Met Asp Tyr
1 5 10 15
<210> 48
<211> 15
<212> PRT
<213> 家鼷鼠
<400> 48
Lys Ala Ser Gln Ser Val Asp Tyr Asp Gly Asp Ser Tyr Met Asn
1 5 10 15
<210> 49
<211> 7
<212> PRT
<213> 家鼷鼠
<400> 49
Ala Ala Ser Asn Leu Glu Ser
1 5
<210> 50
<211> 9
<212> PRT
<213> 家鼷鼠
<400> 50
Gln Gln Ser Asn Glu Asp Pro Trp Thr
1 5
<210> 51
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 合成多肽
<220>
<221> MISC_FEATURE
<223> 兔-小鼠嵌合体
<400> 51
Ser Tyr Trp Met Asn
1 5
<210> 52
<211> 16
<212> PRT
<213> 人工序列
<220>
<223> 合成多肽
<220>
<221> MISC_FEATURE
<223> 兔-小鼠嵌合体
<400> 52
Thr Ile Asp Ser Gly Gly Arg Thr Asp Tyr Ala Ser Trp Ala Lys Gly
1 5 10 15
<210> 53
<211> 4
<212> PRT
<213> 人工序列
<220>
<223> 兔-小鼠嵌合体
<400> 53
Asn Trp Asn Leu
1
<210> 54
<211> 13
<212> PRT
<213> 人工序列
<220>
<223> 合成多肽
<220>
<221> MISC_FEATURE
<223> 兔-小鼠嵌合体
<400> 54
Gln Ser Ser Gln Ser Val Tyr Asp Asn Asn Trp Leu Ala
1 5 10
<210> 55
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 合成多肽
<220>
<221> MISC_FEATURE
<223> 兔-小鼠嵌合体
<400> 55
Asp Ala Ser Asp Leu Ala Ser
1 5
<210> 56
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 合成多肽
<220>
<221> MISC_FEATURE
<223> 兔-小鼠嵌合体
<400> 56
Gln Gly Ala Tyr Asn Asp Val Ile Tyr Ala
1 5 10
<210> 57
<211> 7
<212> PRT
<213> 家鼷鼠
<400> 57
Thr Ser Gly Met Gly Val Gly
1 5
<210> 58
<211> 16
<212> PRT
<213> 家鼷鼠
<400> 58
His Ile Trp Trp Asp Asp Val Lys Arg Tyr Asn Pro Val Leu Lys Ser
1 5 10 15
<210> 59
<211> 14
<212> PRT
<213> 家鼷鼠
<400> 59
Glu Asp Phe Asp Tyr Asp Glu Glu Tyr Tyr Ala Met Asp Tyr
1 5 10
<210> 60
<211> 10
<212> PRT
<213> 家鼷鼠
<400> 60
Ser Ala Ser Ser Ser Val Ser Phe Val Asp
1 5 10
<210> 61
<211> 7
<212> PRT
<213> 家鼷鼠
<400> 61
Arg Thr Ser Asn Leu Gly Phe
1 5
<210> 62
<211> 9
<212> PRT
<213> 家鼷鼠
<400> 62
Gln Gln Arg Ser Thr Tyr Pro Pro Thr
1 5
<210> 63
<211> 20
<212> PRT
<213> 智人
<400> 63
Cys Gly Pro Ala Arg Leu Leu Pro Asn Ala Ile Gly Arg Gly Lys Trp
1 5 10 15
Trp Arg Pro Ser
20
<210> 64
<211> 20
<212> PRT
<213> 智人
<400> 64
Gly Pro Ala Arg Leu Leu Pro Asn Ala Ile Gly Arg Gly Lys Trp Trp
1 5 10 15
Arg Pro Ser Gly
20
<210> 65
<211> 20
<212> PRT
<213> 智人
<400> 65
Pro Ala Arg Leu Leu Pro Asn Ala Ile Gly Arg Gly Lys Trp Trp Arg
1 5 10 15
Pro Ser Gly Pro
20
<210> 66
<211> 20
<212> PRT
<213> 智人
<400> 66
Ala Arg Leu Leu Pro Asn Ala Ile Gly Arg Gly Lys Trp Trp Arg Pro
1 5 10 15
Ser Gly Pro Asp
20
<210> 67
<211> 20
<212> PRT
<213> 智人
<400> 67
Arg Leu Leu Pro Asn Ala Ile Gly Arg Gly Lys Trp Trp Arg Pro Ser
1 5 10 15
Gly Pro Asp Phe
20
<210> 68
<211> 20
<212> PRT
<213> 智人
<400> 68
Leu Leu Pro Asn Ala Ile Gly Arg Gly Lys Trp Trp Arg Pro Ser Gly
1 5 10 15
Pro Asp Phe Arg
20
<210> 69
<211> 20
<212> PRT
<213> 智人
<400> 69
Leu Pro Asn Ala Ile Gly Arg Gly Lys Trp Trp Arg Pro Ser Gly Pro
1 5 10 15
Asp Phe Arg Cys
20
<210> 70
<211> 14
<212> PRT
<213> 智人
<400> 70
Ser Ala Lys Pro Val Thr Glu Leu Val Cys Ser Gly Gln Cys
1 5 10
<210> 71
<211> 7
<212> PRT
<213> 智人
<400> 71
Leu Val Ala Ser Cys Lys Cys
1 5
<210> 72
<211> 8
<212> PRT
<213> 智人
<400> 72
Cys Arg Glu Leu His Phe Thr Arg
1 5
<210> 73
<211> 7
<212> PRT
<213> 智人
<400> 73
Cys Ile Pro Asp Arg Tyr Arg
1 5
<210> 74
<211> 399
<212> DNA
<213> 人工序列
<220>
<223> 合成多核苷酸
<220>
<221> misc_feature
<223> 人源化抗体序列
<400> 74
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
acatttgctc aagttctgac ccagagtcca agcagtctct ccgccagcgt aggcgatcgt 120
gtgactatta cctgtcaatc tagtcagagc gtgtatgata acaattggct ggcgtggtac 180
cagcaaaaac cgggcaaagc cccgaagctg ctcatctatg acgcgtccga tctggctagc 240
ggtgtgccaa gccgtttcag tggcagtggc agcggtactg actttaccct cacaatttcg 300
tctctccagc cggaagattt cgccacttac tattgtcaag gtgcttacaa cgatgtgatt 360
tatgccttcg gtcagggcac taaagtagaa atcaaacgt 399
<210> 75
<211> 133
<212> PRT
<213> 人工序列
<220>
<223> 合成多肽
<220>
<221> MISC_FEATURE
<223> 人源化抗体序列
<400> 75
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Thr Phe Ala Gln Val Leu Thr Gln Ser Pro Ser Ser
20 25 30
Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Gln Ser Ser
35 40 45
Gln Ser Val Tyr Asp Asn Asn Trp Leu Ala Trp Tyr Gln Gln Lys Pro
50 55 60
Gly Lys Ala Pro Lys Leu Leu Ile Tyr Asp Ala Ser Asp Leu Ala Ser
65 70 75 80
Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr
85 90 95
Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys
100 105 110
Gln Gly Ala Tyr Asn Asp Val Ile Tyr Ala Phe Gly Gln Gly Thr Lys
115 120 125
Val Glu Ile Lys Arg
130
<210> 76
<211> 393
<212> DNA
<213> 人工序列
<220>
<223> 合成多核苷酸
<220>
<221> misc_feature
<223> 人源化抗体序列
<400> 76
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccactgtgag 60
gtgcagctgt tggagtctgg aggcgggctt gtccagcctg gagggagcct gcgtctctct 120
tgtgcagcaa gcggcttcag cttatcctct tactggatga attgggtgcg gcaggcacct 180
gggaagggcc tggagtgggt gggcaccatt gattccggag gccgtacaga ctacgcgtct 240
tgggcaaagg gccgtttcac catttcccgc gacaactcca aaaataccat gtacctccag 300
atgaactctc tccgcgcaga ggacacagca cgttattact gtgcacgcaa ctggaatctg 360
tggggtcaag gtactcttgt aacagtctcg agc 393
<210> 77
<211> 131
<212> PRT
<213> 人工序列
<220>
<223> 合成多肽
<220>
<221> MISC_FEATURE
<223> 人源化抗体序列
<400> 77
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val His Cys Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln
20 25 30
Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Leu
35 40 45
Ser Ser Tyr Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Glu Trp Val Gly Thr Ile Asp Ser Gly Gly Arg Thr Asp Tyr Ala Ser
65 70 75 80
Trp Ala Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr
85 90 95
Met Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Arg Tyr
100 105 110
Tyr Cys Ala Arg Asn Trp Asn Leu Trp Gly Gln Gly Thr Leu Val Thr
115 120 125
Val Ser Ser
130
<210> 78
<211> 11
<212> PRT
<213> 家鼷鼠
<400> 78
Arg Ala Ser Gln Asp Ile Ser Asn Tyr Leu Asn
1 5 10
<210> 79
<211> 7
<212> PRT
<213> 家鼷鼠
<400> 79
Tyr Thr Ser Arg Leu Leu Ser
1 5
<210> 80
<211> 9
<212> PRT
<213> 家鼷鼠
<400> 80
Gln Gln Gly Asp Thr Leu Pro Tyr Thr
1 5
<210> 81
<211> 11
<212> PRT
<213> 家鼷鼠
<400> 81
Arg Ala Ser Gln Asp Ile Ser Asn Tyr Leu Asn
1 5 10
<210> 82
<211> 24
<212> PRT
<213> 沟鼠
<400> 82
Gln Gly Trp Gln Ala Phe Lys Asn Asp Ala Thr Glu Ile Ile Pro Gly
1 5 10 15
Leu Arg Glu Tyr Pro Glu Pro Pro
20
<210> 83
<211> 20
<212> PRT
<213> 沟鼠
<400> 83
Thr Glu Ile Ile Pro Gly Leu Arg Glu Tyr Pro Glu Pro Pro Gln Glu
1 5 10 15
Leu Glu Asn Asn
20
<210> 84
<211> 20
<212> PRT
<213> 沟鼠
<400> 84
Pro Glu Pro Pro Gln Glu Leu Glu Asn Asn Gln Thr Met Asn Arg Ala
1 5 10 15
Glu Asn Gly Gly
20
<210> 85
<211> 20
<212> PRT
<213> 沟鼠
<400> 85
Glu Asn Gly Gly Arg Pro Pro His His Pro Tyr Asp Thr Lys Asp Val
1 5 10 15
Ser Glu Tyr Ser
20
<210> 86
<211> 14
<212> PRT
<213> 沟鼠
<400> 86
Cys Arg Glu Leu His Tyr Thr Arg Phe Val Thr Asp Gly Pro
1 5 10
<210> 87
<211> 25
<212> PRT
<213> 沟鼠
<400> 87
Cys Arg Glu Leu His Tyr Thr Arg Phe Val Thr Asp Gly Pro Ser Arg
1 5 10 15
Ser Ala Lys Pro Val Thr Glu Leu Val
20 25
<210> 88
<211> 23
<212> PRT
<213> 沟鼠
<400> 88
Cys Arg Ser Ala Lys Pro Val Thr Glu Leu Val Ser Ser Gly Gln Ser
1 5 10 15
Gly Pro Arg Ala Arg Leu Leu
20
<210> 89
<211> 25
<212> PRT
<213> 沟鼠
<400> 89
Cys Gly Pro Ala Arg Leu Leu Pro Asn Ala Ile Gly Arg Val Lys Trp
1 5 10 15
Trp Arg Pro Asn Gly Pro Asp Phe Arg
20 25
<210> 90
<211> 20
<212> PRT
<213> 沟鼠
<400> 90
Arg Ala Gln Arg Val Gln Leu Leu Cys Pro Gly Gly Ala Ala Pro Arg
1 5 10 15
Ser Arg Lys Val
20
<210> 91
<211> 16
<212> PRT
<213> 沟鼠
<400> 91
Pro Gly Gly Ala Ala Pro Arg Ser Arg Lys Val Arg Leu Val Ala Ser
1 5 10 15
<210> 92
<211> 23
<212> PRT
<213> 沟鼠
<400> 92
Lys Arg Leu Thr Arg Phe His Asn Gln Ser Glu Leu Lys Asp Phe Gly
1 5 10 15
Pro Glu Thr Ala Arg Pro Gln
20
<210> 93
<211> 16
<212> PRT
<213> 沟鼠
<400> 93
Ile Pro Asp Arg Tyr Ala Gln Arg Val Gln Leu Leu Ser Pro Gly Gly
1 5 10 15
<210> 94
<211> 24
<212> PRT
<213> 沟鼠
<400> 94
Ser Glu Leu Lys Asp Phe Gly Pro Glu Thr Ala Arg Pro Gln Lys Gly
1 5 10 15
Arg Lys Pro Arg Pro Arg Ala Arg
20
<210> 95
<211> 23
<212> PRT
<213> 沟鼠
<400> 95
Lys Gly Arg Lys Pro Arg Pro Arg Ala Arg Gly Ala Lys Ala Asn Gln
1 5 10 15
Ala Glu Leu Glu Asn Ala Tyr
20
<210> 96
<211> 18
<212> PRT
<213> 沟鼠
<400> 96
Pro Asn Ala Ile Gly Arg Val Lys Trp Trp Arg Pro Asn Gly Pro Asp
1 5 10 15
Phe Arg
<210> 97
<211> 22
<212> PRT
<213> 沟鼠
<400> 97
Lys Trp Trp Arg Pro Asn Gly Pro Asp Phe Arg Cys Ile Pro Asp Arg
1 5 10 15
Tyr Arg Ala Gln Arg Val
20
<210> 98
<211> 213
<212> PRT
<213> 沟鼠
<400> 98
Met Gln Leu Ser Leu Ala Pro Cys Leu Ala Cys Leu Leu Val His Ala
1 5 10 15
Ala Phe Val Ala Val Glu Ser Gln Gly Trp Gln Ala Phe Lys Asn Asp
20 25 30
Ala Thr Glu Ile Ile Pro Gly Leu Arg Glu Tyr Pro Glu Pro Pro Gln
35 40 45
Glu Leu Glu Asn Asn Gln Thr Met Asn Arg Ala Glu Asn Gly Gly Arg
50 55 60
Pro Pro His His Pro Tyr Asp Thr Lys Asp Val Ser Glu Tyr Ser Cys
65 70 75 80
Arg Glu Leu His Tyr Thr Arg Phe Val Thr Asp Gly Pro Cys Arg Ser
85 90 95
Ala Lys Pro Val Thr Glu Leu Val Cys Ser Gly Gln Cys Gly Pro Ala
100 105 110
Arg Leu Leu Pro Asn Ala Ile Gly Arg Val Lys Trp Trp Arg Pro Asn
115 120 125
Gly Pro Asp Phe Arg Cys Ile Pro Asp Arg Tyr Arg Ala Gln Arg Val
130 135 140
Gln Leu Leu Cys Pro Gly Gly Ala Ala Pro Arg Ser Arg Lys Val Arg
145 150 155 160
Leu Val Ala Ser Cys Lys Cys Lys Arg Leu Thr Arg Phe His Asn Gln
165 170 175
Ser Glu Leu Lys Asp Phe Gly Pro Glu Thr Ala Arg Pro Gln Lys Gly
180 185 190
Arg Lys Pro Arg Pro Arg Ala Arg Gly Ala Lys Ala Asn Gln Ala Glu
195 200 205
Leu Glu Asn Ala Tyr
210
<210> 99
<211> 7
<212> PRT
<213> 家鼷鼠
<400> 99
Tyr Thr Ser Arg Leu His Ser
1 5
<210> 100
<211> 9
<212> PRT
<213> 家鼷鼠
<400> 100
Gln Gln Gly Asp Thr Leu Pro Tyr Thr
1 5
<210> 101
<211> 11
<212> PRT
<213> 家鼷鼠
<400> 101
Arg Ala Ser Gln Val Ile Thr Asn Tyr Leu Tyr
1 5 10
<210> 102
<211> 7
<212> PRT
<213> 家鼷鼠
<400> 102
Tyr Thr Ser Arg Leu His Ser
1 5
<210> 103
<211> 9
<212> PRT
<213> 家鼷鼠
<400> 103
Gln Gln Gly Asp Thr Leu Pro Tyr Thr
1 5
<210> 104
<211> 11
<212> PRT
<213> 家鼷鼠
<400> 104
Arg Ala Ser Gln Asp Ile Ser Asn Tyr Leu Asn
1 5 10
<210> 105
<211> 7
<212> PRT
<213> 家鼷鼠
<400> 105
Tyr Thr Ser Arg Leu Leu Ser
1 5
<210> 106
<211> 9
<212> PRT
<213> 家鼷鼠
<400> 106
Gln Gln Gly Asp Thr Leu Pro Tyr Thr
1 5
<210> 107
<211> 11
<212> PRT
<213> 家鼷鼠
<400> 107
Arg Ala Ser Gln Asp Ile Ser Asn Tyr Leu Asn
1 5 10
<210> 108
<211> 7
<212> PRT
<213> 家鼷鼠
<400> 108
Tyr Thr Ser Arg Leu Phe Ser
1 5
<210> 109
<211> 9
<212> PRT
<213> 家鼷鼠
<400> 109
Gln Gln Gly Asp Thr Leu Pro Tyr Thr
1 5
<210> 110
<211> 11
<212> PRT
<213> 家鼷鼠
<400> 110
Arg Ala Ser Gln Asp Ile Ser Asn Tyr Leu Asn
1 5 10
<210> 111
<211> 7
<212> PRT
<213> 家鼷鼠
<400> 111
Tyr Thr Ser Arg Leu Leu Ser
1 5
<210> 112
<211> 9
<212> PRT
<213> 家鼷鼠
<400> 112
Gln Gln Gly Asp Thr Leu Pro Tyr Thr
1 5
<210> 113
<211> 11
<212> PRT
<213> 家鼷鼠
<400> 113
Arg Ala Ser Gln Asp Ile Ser Asn Tyr Leu Asn
1 5 10
<210> 114
<211> 7
<212> PRT
<213> 家鼷鼠
<400> 114
Tyr Thr Ser Thr Leu Gln Ser
1 5
<210> 115
<211> 9
<212> PRT
<213> 家鼷鼠
<400> 115
Gln Gln Gly Asp Thr Leu Pro Tyr Thr
1 5
<210> 116
<211> 12
<212> PRT
<213> 家鼷鼠
<400> 116
Ser Val Ser Ser Ser Ile Ser Ser Ser Asn Leu His
1 5 10
<210> 117
<211> 213
<212> PRT
<213> 家鼷鼠
<400> 117
Gln Ile Val Leu Ser Gln Ser Pro Ala Ile Leu Ser Thr Ser Pro Gly
1 5 10 15
Glu Lys Val Thr Met Thr Cys Arg Ala Ser Ser Ser Val Tyr Tyr Met
20 25 30
His Trp Tyr Gln Gln Lys Pro Gly Ser Ser Pro Lys Pro Trp Ile Tyr
35 40 45
Ala Thr Ser Asn Leu Ala Ser Gly Val Pro Val Arg Phe Ser Gly Ser
50 55 60
Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile Thr Arg Val Glu Ala Glu
65 70 75 80
Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Trp Ser Ser Asp Pro Leu Thr
85 90 95
Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys Arg Ala Asp Ala Ala Pro
100 105 110
Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln Leu Thr Ser Gly Gly
115 120 125
Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr Pro Lys Asp Ile Asn
130 135 140
Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln Asn Gly Val Leu Asn
145 150 155 160
Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr Tyr Ser Met Ser Ser
165 170 175
Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg His Asn Ser Tyr Thr
180 185 190
Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro Ile Val Lys Ser Phe
195 200 205
Asn Arg Asn Glu Cys
210
<210> 118
<211> 642
<212> DNA
<213> 家鼷鼠
<400> 118
caaattgttc tctcccagtc tccagcaatc ctgtctacat ctccagggga gaaggtcaca 60
atgacttgca gggccagctc aagtgtatat tacatgcact ggtaccagca gaagccagga 120
tcctccccca aaccctggat ttatgccaca tccaacctgg cttctggagt ccctgttcgc 180
ttcagtggca gtgggtctgg gacctcttac tctctcacaa tcaccagagt ggaggctgaa 240
gatgctgcca cttattactg ccagcagtgg agtagtgacc cactcacgtt cggtgctggg 300
accaagctgg agctgaaacg ggctgatgct gcaccaactg tatccatctt cccaccatcc 360
agtgagcagt taacatctgg aggtgcctca gtcgtgtgct tcttgaacaa cttctacccc 420
aaagacatca atgtcaagtg gaagattgat ggcagtgaac gacaaaatgg cgtcctgaac 480
agttggactg atcaggacag caaagacagc acctacagca tgagcagcac cctcacgttg 540
accaaggacg agtatgaacg acataacagc tatacctgtg aggccactca caagacatca 600
acttcaccca ttgtcaagag cttcaacagg aatgagtgtt ag 642
<210> 119
<211> 235
<212> PRT
<213> 家鼷鼠
<400> 119
Met Asp Phe Gln Val Gln Ile Phe Ser Phe Leu Leu Ile Ser Ala Ser
1 5 10 15
Val Ile Met Ser Arg Gly Gln Ile Val Leu Ser Gln Ser Pro Ala Ile
20 25 30
Leu Ser Thr Ser Pro Gly Glu Lys Val Thr Met Thr Cys Arg Ala Ser
35 40 45
Ser Ser Val Tyr Tyr Met His Trp Tyr Gln Gln Lys Pro Gly Ser Ser
50 55 60
Pro Lys Pro Trp Ile Tyr Ala Thr Ser Asn Leu Ala Ser Gly Val Pro
65 70 75 80
Val Arg Phe Ser Gly Ser Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile
85 90 95
Thr Arg Val Glu Ala Glu Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Trp
100 105 110
Ser Ser Asp Pro Leu Thr Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys
115 120 125
Arg Ala Asp Ala Ala Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu
130 135 140
Gln Leu Thr Ser Gly Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe
145 150 155 160
Tyr Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg
165 170 175
Gln Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser
180 185 190
Thr Tyr Ser Met Ser Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu
195 200 205
Arg His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser
210 215 220
Pro Ile Val Lys Ser Phe Asn Arg Asn Glu Cys
225 230 235
<210> 120
<211> 708
<212> DNA
<213> 家鼷鼠
<400> 120
atggattttc aagtgcagat tttcagcttc ctgctaatca gtgcttcagt cattatgtcc 60
aggggacaaa ttgttctctc ccagtctcca gcaatcctgt ctacatctcc aggggagaag 120
gtcacaatga cttgcagggc cagctcaagt gtatattaca tgcactggta ccagcagaag 180
ccaggatcct cccccaaacc ctggatttat gccacatcca acctggcttc tggagtccct 240
gttcgcttca gtggcagtgg gtctgggacc tcttactctc tcacaatcac cagagtggag 300
gctgaagatg ctgccactta ttactgccag cagtggagta gtgacccact cacgttcggt 360
gctgggacca agctggagct gaaacgggct gatgctgcac caactgtatc catcttccca 420
ccatccagtg agcagttaac atctggaggt gcctcagtcg tgtgcttctt gaacaacttc 480
taccccaaag acatcaatgt caagtggaag attgatggca gtgaacgaca aaatggcgtc 540
ctgaacagtt ggactgatca ggacagcaaa gacagcacct acagcatgag cagcaccctc 600
acgttgacca aggacgagta tgaacgacat aacagctata cctgtgaggc cactcacaag 660
acatcaactt cacccattgt caagagcttc aacaggaatg agtgttag 708
<210> 121
<211> 445
<212> PRT
<213> 家鼷鼠
<400> 121
Glu Val Gln Val Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Leu Ser Cys Thr Ala Ser Gly Phe Asn Ile Lys Asp Tyr
20 25 30
Phe Ile His Trp Val Lys Gln Arg Pro Glu Gln Gly Leu Glu Trp Ile
35 40 45
Gly Arg Leu Asp Pro Glu Asp Gly Glu Ser Asp Tyr Ala Pro Lys Phe
50 55 60
Gln Asp Lys Ala Ile Met Thr Ala Asp Thr Ser Ser Asn Thr Ala Tyr
65 70 75 80
Leu Gln Leu Arg Ser Leu Thr Ser Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Glu Arg Glu Asp Tyr Asp Gly Thr Tyr Thr Phe Phe Pro Tyr Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ala Ala Lys Thr Thr Pro Pro Ser
115 120 125
Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr Asn Ser Met Val
130 135 140
Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val Thr Val
145 150 155 160
Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr Phe Pro Ala
165 170 175
Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr Val Pro
180 185 190
Ser Ser Thr Trp Pro Ser Glu Thr Val Thr Cys Asn Val Ala His Pro
195 200 205
Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val Pro Arg Asp Cys Gly
210 215 220
Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser Ser Val Phe Ile
225 230 235 240
Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro Lys
245 250 255
Val Thr Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu Val Gln
260 265 270
Phe Ser Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr Gln
275 280 285
Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser Glu Leu
290 295 300
Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg
305 310 315 320
Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys
325 330 335
Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro
340 345 350
Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile Thr
355 360 365
Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly Gln
370 375 380
Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr Asp Gly
385 390 395 400
Ser Tyr Phe Ile Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn Trp Glu
405 410 415
Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His Asn
420 425 430
His His Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys
435 440 445
<210> 122
<211> 1338
<212> DNA
<213> 家鼷鼠
<400> 122
gaggttcagg tgcagcagtc tgggccagaa cttgtgaagc caggggcctc agtcaagttg 60
tcctgcacag cttctggctt caacattaaa gactacttta tacactgggt gaagcagagg 120
cctgaacagg gcctggagtg gattggaagg cttgatcctg aggatggtga aagtgattat 180
gccccgaagt tccaggacaa ggccattatg acagcagaca catcatccaa cacagcctat 240
cttcagctca gaagcctgac atctgaggac actgccatct attattgtga gagagaggac 300
tacgatggta cctacacctt ttttccttac tggggccaag ggactctggt cactgtctct 360
gcagccaaaa cgacaccccc atctgtctat ccactggccc ctggatctgc tgcccaaact 420
aactccatgg tgaccctggg atgcctggtc aagggctatt tccctgagcc agtgacagtg 480
acctggaact ctggatccct gtccagcggt gtgcacacct tcccagctgt cctgcagtct 540
gacctctaca ctctgagcag ctcagtgact gtcccctcca gcacctggcc cagcgagacc 600
gtcacctgca acgttgccca cccggccagc agcaccaagg tggacaagaa aattgtgccc 660
agggattgtg gttgtaagcc ttgcatatgt acagtcccag aagtatcatc tgtcttcatc 720
ttccccccaa agcccaagga tgtgctcacc attactctga ctcctaaggt cacgtgtgtt 780
gtggtagaca tcagcaagga tgatcccgag gtccagttca gctggtttgt agatgatgtg 840
gaggtgcaca cagctcagac gcaaccccgg gaggagcagt tcaacagcac tttccgctca 900
gtcagtgaac ttcccatcat gcaccaggac tggctcaatg gcaaggagtt caaatgcagg 960
gtcaacagtg cagctttccc tgcccccatc gagaaaacca tctccaaaac caaaggcaga 1020
ccgaaggctc cacaggtgta caccattcca cctcccaagg agcagatggc caaggataaa 1080
gtcagtctga cctgcatgat aacagacttc ttccctgaag acattactgt ggagtggcag 1140
tggaatgggc agccagcgga gaactacaag aacactcagc ccatcatgga cacagatggc 1200
tcttacttca tctacagcaa gctcaatgtg cagaagagca actgggaggc aggaaatact 1260
ttcacctgct ctgtgttaca tgagggcctg cacaaccacc atactgagaa gagcctctcc 1320
cactctcctg gtaaatga 1338
<210> 123
<211> 464
<212> PRT
<213> 家鼷鼠
<400> 123
Met Lys Cys Ser Trp Val Ile Phe Phe Leu Met Ala Val Val Thr Gly
1 5 10 15
Val Asn Ser Glu Val Gln Val Gln Gln Ser Gly Pro Glu Leu Val Lys
20 25 30
Pro Gly Ala Ser Val Lys Leu Ser Cys Thr Ala Ser Gly Phe Asn Ile
35 40 45
Lys Asp Tyr Phe Ile His Trp Val Lys Gln Arg Pro Glu Gln Gly Leu
50 55 60
Glu Trp Ile Gly Arg Leu Asp Pro Glu Asp Gly Glu Ser Asp Tyr Ala
65 70 75 80
Pro Lys Phe Gln Asp Lys Ala Ile Met Thr Ala Asp Thr Ser Ser Asn
85 90 95
Thr Ala Tyr Leu Gln Leu Arg Ser Leu Thr Ser Glu Asp Thr Ala Ile
100 105 110
Tyr Tyr Cys Glu Arg Glu Asp Tyr Asp Gly Thr Tyr Thr Phe Phe Pro
115 120 125
Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala Ala Lys Thr Thr
130 135 140
Pro Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr Asn
145 150 155 160
Ser Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro
165 170 175
Val Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr
180 185 190
Phe Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val
195 200 205
Thr Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val Thr Cys Asn Val
210 215 220
Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val Pro Arg
225 230 235 240
Asp Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser Ser
245 250 255
Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu
260 265 270
Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro
275 280 285
Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His Thr Ala
290 295 300
Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val
305 310 315 320
Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe
325 330 335
Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr
340 345 350
Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile
355 360 365
Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys
370 375 380
Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp
385 390 395 400
Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp
405 410 415
Thr Asp Gly Ser Tyr Phe Ile Tyr Ser Lys Leu Asn Val Gln Lys Ser
420 425 430
Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly
435 440 445
Leu His Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys
450 455 460
<210> 124
<211> 1395
<212> DNA
<213> 家鼷鼠
<400> 124
atgaaatgca gctgggtcat cttcttcctg atggcagtgg ttacaggggt caattcagag 60
gttcaggtgc agcagtctgg gccagaactt gtgaagccag gggcctcagt caagttgtcc 120
tgcacagctt ctggcttcaa cattaaagac tactttatac actgggtgaa gcagaggcct 180
gaacagggcc tggagtggat tggaaggctt gatcctgagg atggtgaaag tgattatgcc 240
ccgaagttcc aggacaaggc cattatgaca gcagacacat catccaacac agcctatctt 300
cagctcagaa gcctgacatc tgaggacact gccatctatt attgtgagag agaggactac 360
gatggtacct acaccttttt tccttactgg ggccaaggga ctctggtcac tgtctctgca 420
gccaaaacga cacccccatc tgtctatcca ctggcccctg gatctgctgc ccaaactaac 480
tccatggtga ccctgggatg cctggtcaag ggctatttcc ctgagccagt gacagtgacc 540
tggaactctg gatccctgtc cagcggtgtg cacaccttcc cagctgtcct gcagtctgac 600
ctctacactc tgagcagctc agtgactgtc ccctccagca cctggcccag cgagaccgtc 660
acctgcaacg ttgcccaccc ggccagcagc accaaggtgg acaagaaaat tgtgcccagg 720
gattgtggtt gtaagccttg catatgtaca gtcccagaag tatcatctgt cttcatcttc 780
cccccaaagc ccaaggatgt gctcaccatt actctgactc ctaaggtcac gtgtgttgtg 840
gtagacatca gcaaggatga tcccgaggtc cagttcagct ggtttgtaga tgatgtggag 900
gtgcacacag ctcagacgca accccgggag gagcagttca acagcacttt ccgctcagtc 960
agtgaacttc ccatcatgca ccaggactgg ctcaatggca aggagttcaa atgcagggtc 1020
aacagtgcag ctttccctgc ccccatcgag aaaaccatct ccaaaaccaa aggcagaccg 1080
aaggctccac aggtgtacac cattccacct cccaaggagc agatggccaa ggataaagtc 1140
agtctgacct gcatgataac agacttcttc cctgaagaca ttactgtgga gtggcagtgg 1200
aatgggcagc cagcggagaa ctacaagaac actcagccca tcatggacac agatggctct 1260
tacttcatct acagcaagct caatgtgcag aagagcaact gggaggcagg aaatactttc 1320
acctgctctg tgttacatga gggcctgcac aaccaccata ctgagaagag cctctcccac 1380
tctcctggta aatga 1395
<210> 125
<211> 215
<212> PRT
<213> 家鼷鼠
<400> 125
Glu Ile Val Leu Thr Gln Ser Pro Ala Leu Met Ala Ala Ser Pro Gly
1 5 10 15
Glu Lys Val Thr Ile Thr Cys Ser Val Ser Ser Thr Ile Ser Ser Asn
20 25 30
His Leu His Trp Phe Gln Gln Lys Ser Asp Thr Ser Pro Lys Pro Trp
35 40 45
Ile Tyr Gly Thr Ser Asn Leu Ala Ser Gly Val Pro Val Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile Ser Ser Met Glu
65 70 75 80
Ala Glu Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Trp Ser Ser Tyr Pro
85 90 95
Leu Thr Phe Gly Ala Gly Thr Lys Leu Glu Leu Arg Arg Ala Asp Ala
100 105 110
Ala Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln Leu Thr Ser
115 120 125
Gly Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr Pro Lys Asp
130 135 140
Ile Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln Asn Gly Val
145 150 155 160
Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr Tyr Ser Met
165 170 175
Ser Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg His Asn Ser
180 185 190
Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro Ile Val Lys
195 200 205
Ser Phe Asn Arg Asn Glu Cys
210 215
<210> 126
<211> 648
<212> DNA
<213> 家鼷鼠
<400> 126
gaaattgtgc tcacccagtc tccagcactc atggctgcat ctccggggga gaaggtcacc 60
atcacctgca gtgtcagttc aactataagt tccaaccact tgcactggtt ccagcagaag 120
tcagacacct cccccaaacc ctggatttat ggcacatcca acctggcttc tggagtccct 180
gttcgcttca gtggcagtgg atctgggacc tcttattctc tcacaatcag cagcatggag 240
gctgaggatg ctgccactta ttactgtcaa cagtggagta gttacccact cacgttcggc 300
gctgggacca agctggagct gagacgggct gatgctgcac caactgtatc catcttccca 360
ccatccagtg agcagttaac atctggaggt gcctcagtcg tgtgcttctt gaacaacttc 420
taccccaaag acatcaatgt caagtggaag attgatggca gtgaacgaca aaatggcgtc 480
ctgaacagtt ggactgatca ggacagcaaa gacagcacct acagcatgag cagcaccctc 540
acgttgacca aggacgagta tgaacgacat aacagctata cctgtgaggc cactcacaag 600
acatcaactt cacccattgt caagagcttc aacaggaatg agtgttag 648
<210> 127
<211> 237
<212> PRT
<213> 家鼷鼠
<400> 127
Met Asp Phe His Val Gln Ile Phe Ser Phe Met Leu Ile Ser Val Thr
1 5 10 15
Val Ile Leu Ser Ser Gly Glu Ile Val Leu Thr Gln Ser Pro Ala Leu
20 25 30
Met Ala Ala Ser Pro Gly Glu Lys Val Thr Ile Thr Cys Ser Val Ser
35 40 45
Ser Thr Ile Ser Ser Asn His Leu His Trp Phe Gln Gln Lys Ser Asp
50 55 60
Thr Ser Pro Lys Pro Trp Ile Tyr Gly Thr Ser Asn Leu Ala Ser Gly
65 70 75 80
Val Pro Val Arg Phe Ser Gly Ser Gly Ser Gly Thr Ser Tyr Ser Leu
85 90 95
Thr Ile Ser Ser Met Glu Ala Glu Asp Ala Ala Thr Tyr Tyr Cys Gln
100 105 110
Gln Trp Ser Ser Tyr Pro Leu Thr Phe Gly Ala Gly Thr Lys Leu Glu
115 120 125
Leu Arg Arg Ala Asp Ala Ala Pro Thr Val Ser Ile Phe Pro Pro Ser
130 135 140
Ser Glu Gln Leu Thr Ser Gly Gly Ala Ser Val Val Cys Phe Leu Asn
145 150 155 160
Asn Phe Tyr Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly Ser
165 170 175
Glu Arg Gln Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys
180 185 190
Asp Ser Thr Tyr Ser Met Ser Ser Thr Leu Thr Leu Thr Lys Asp Glu
195 200 205
Tyr Glu Arg His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr Ser
210 215 220
Thr Ser Pro Ile Val Lys Ser Phe Asn Arg Asn Glu Cys
225 230 235
<210> 128
<211> 714
<212> DNA
<213> 家鼷鼠
<400> 128
atggattttc atgtgcagat tttcagcttc atgctaatca gtgtcacagt cattttgtcc 60
agtggagaaa ttgtgctcac ccagtctcca gcactcatgg ctgcatctcc gggggagaag 120
gtcaccatca cctgcagtgt cagttcaact ataagttcca accacttgca ctggttccag 180
cagaagtcag acacctcccc caaaccctgg atttatggca catccaacct ggcttctgga 240
gtccctgttc gcttcagtgg cagtggatct gggacctctt attctctcac aatcagcagc 300
atggaggctg aggatgctgc cacttattac tgtcaacagt ggagtagtta cccactcacg 360
ttcggcgctg ggaccaagct ggagctgaga cgggctgatg ctgcaccaac tgtatccatc 420
ttcccaccat ccagtgagca gttaacatct ggaggtgcct cagtcgtgtg cttcttgaac 480
aacttctacc ccaaagacat caatgtcaag tggaagattg atggcagtga acgacaaaat 540
ggcgtcctga acagttggac tgatcaggac agcaaagaca gcacctacag catgagcagc 600
accctcacgt tgaccaagga cgagtatgaa cgacataaca gctatacctg tgaggccact 660
cacaagacat caacttcacc cattgtcaag agcttcaaca ggaatgagtg ttag 714
<210> 129
<211> 449
<212> PRT
<213> 家鼷鼠
<400> 129
Glu Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Leu Val Lys Leu Ser Cys Thr Ala Ser Asp Phe Asn Ile Lys Asp Phe
20 25 30
Tyr Leu His Trp Met Arg Gln Arg Pro Glu Gln Gly Leu Asp Trp Ile
35 40 45
Gly Arg Ile Asp Pro Glu Asn Gly Asp Thr Leu Tyr Asp Pro Lys Phe
50 55 60
Gln Asp Lys Ala Thr Leu Thr Thr Asp Thr Ser Ser Asn Thr Ala Tyr
65 70 75 80
Leu Gln Leu Ser Gly Leu Thr Ser Glu Thr Thr Ala Val Tyr Tyr Cys
85 90 95
Ser Arg Glu Ala Asp Tyr Phe His Asp Gly Thr Ser Tyr Trp Tyr Phe
100 105 110
Asp Val Trp Gly Ala Gly Thr Thr Ile Thr Val Ser Ser Ala Lys Thr
115 120 125
Thr Pro Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr
130 135 140
Asn Ser Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu
145 150 155 160
Pro Val Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His
165 170 175
Thr Phe Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser
180 185 190
Val Thr Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val Thr Cys Asn
195 200 205
Val Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val Pro
210 215 220
Arg Asp Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser
225 230 235 240
Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr
245 250 255
Leu Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp Asp
260 265 270
Pro Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His Thr
275 280 285
Ala Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser
290 295 300
Val Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu
305 310 315 320
Phe Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys
325 330 335
Thr Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr
340 345 350
Ile Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr
355 360 365
Cys Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln
370 375 380
Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met
385 390 395 400
Asp Thr Asp Gly Ser Tyr Phe Ile Tyr Ser Lys Leu Asn Val Gln Lys
405 410 415
Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu
420 425 430
Gly Leu His Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro Gly
435 440 445
Lys
<210> 130
<211> 1350
<212> DNA
<213> 家鼷鼠
<400> 130
gaggttcagc tgcagcagtc tggggctgaa cttgtgaggc caggggcctt agtcaagttg 60
tcctgcacag cttctgactt caacattaaa gacttctatc tacactggat gaggcagcgg 120
cctgaacagg gcctggactg gattggaagg attgatcctg agaatggtga tactttatat 180
gacccgaagt tccaggacaa ggccactctt acaacagaca catcctccaa cacagcctac 240
ctgcagctca gcggcctgac atctgagacc actgccgtct attactgttc tagagaggcg 300
gattatttcc acgatggtac ctcctactgg tacttcgatg tctggggcgc agggaccaca 360
atcaccgtct cctcagccaa aacgacaccc ccatctgtct atccactggc ccctggatct 420
gctgcccaaa ctaactccat ggtgaccctg ggatgcctgg tcaagggcta tttccctgag 480
ccagtgacag tgacctggaa ctctggatcc ctgtccagcg gtgtgcacac cttcccagct 540
gtcctgcagt ctgacctcta cactctgagc agctcagtga ctgtcccctc cagcacctgg 600
cccagcgaga ccgtcacctg caacgttgcc cacccggcca gcagcaccaa ggtggacaag 660
aaaattgtgc ccagggattg tggttgtaag ccttgcatat gtacagtccc agaagtatca 720
tctgtcttca tcttcccccc aaagcccaag gatgtgctca ccattactct gactcctaag 780
gtcacgtgtg ttgtggtaga catcagcaag gatgatcccg aggtccagtt cagctggttt 840
gtagatgatg tggaggtgca cacagctcag acgcaacccc gggaggagca gttcaacagc 900
actttccgct cagtcagtga acttcccatc atgcaccagg actggctcaa tggcaaggag 960
ttcaaatgca gggtcaacag tgcagctttc cctgccccca tcgagaaaac catctccaaa 1020
accaaaggca gaccgaaggc tccacaggtg tacaccattc cacctcccaa ggagcagatg 1080
gccaaggata aagtcagtct gacctgcatg ataacagact tcttccctga agacattact 1140
gtggagtggc agtggaatgg gcagccagcg gagaactaca agaacactca gcccatcatg 1200
gacacagatg gctcttactt catctacagc aagctcaatg tgcagaagag caactgggag 1260
gcaggaaata ctttcacctg ctctgtgtta catgagggcc tgcacaacca ccatactgag 1320
aagagcctct cccactctcc tggtaaatga 1350
<210> 131
<211> 468
<212> PRT
<213> 家鼷鼠
<400> 131
Met Lys Cys Ser Trp Val Ile Phe Phe Leu Met Ala Val Val Thr Gly
1 5 10 15
Val Asn Ser Glu Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg
20 25 30
Pro Gly Ala Leu Val Lys Leu Ser Cys Thr Ala Ser Asp Phe Asn Ile
35 40 45
Lys Asp Phe Tyr Leu His Trp Met Arg Gln Arg Pro Glu Gln Gly Leu
50 55 60
Asp Trp Ile Gly Arg Ile Asp Pro Glu Asn Gly Asp Thr Leu Tyr Asp
65 70 75 80
Pro Lys Phe Gln Asp Lys Ala Thr Leu Thr Thr Asp Thr Ser Ser Asn
85 90 95
Thr Ala Tyr Leu Gln Leu Ser Gly Leu Thr Ser Glu Thr Thr Ala Val
100 105 110
Tyr Tyr Cys Ser Arg Glu Ala Asp Tyr Phe His Asp Gly Thr Ser Tyr
115 120 125
Trp Tyr Phe Asp Val Trp Gly Ala Gly Thr Thr Ile Thr Val Ser Ser
130 135 140
Ala Lys Thr Thr Pro Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala
145 150 155 160
Ala Gln Thr Asn Ser Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr
165 170 175
Phe Pro Glu Pro Val Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser
180 185 190
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu
195 200 205
Ser Ser Ser Val Thr Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val
210 215 220
Thr Cys Asn Val Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys
225 230 235 240
Ile Val Pro Arg Asp Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro
245 250 255
Glu Val Ser Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu
260 265 270
Thr Ile Thr Leu Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser
275 280 285
Lys Asp Asp Pro Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu
290 295 300
Val His Thr Ala Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr
305 310 315 320
Phe Arg Ser Val Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn
325 330 335
Gly Lys Glu Phe Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro
340 345 350
Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln
355 360 365
Val Tyr Thr Ile Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val
370 375 380
Ser Leu Thr Cys Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val
385 390 395 400
Glu Trp Gln Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln
405 410 415
Pro Ile Met Asp Thr Asp Gly Ser Tyr Phe Ile Tyr Ser Lys Leu Asn
420 425 430
Val Gln Lys Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val
435 440 445
Leu His Glu Gly Leu His Asn His His Thr Glu Lys Ser Leu Ser His
450 455 460
Ser Pro Gly Lys
465
<210> 132
<211> 1407
<212> DNA
<213> 家鼷鼠
<400> 132
atgaaatgca gctgggtcat cttcttcctg atggcagtgg ttacaggggt caattcagag 60
gttcagctgc agcagtctgg ggctgaactt gtgaggccag gggccttagt caagttgtcc 120
tgcacagctt ctgacttcaa cattaaagac ttctatctac actggatgag gcagcggcct 180
gaacagggcc tggactggat tggaaggatt gatcctgaga atggtgatac tttatatgac 240
ccgaagttcc aggacaaggc cactcttaca acagacacat cctccaacac agcctacctg 300
cagctcagcg gcctgacatc tgagaccact gccgtctatt actgttctag agaggcggat 360
tatttccacg atggtacctc ctactggtac ttcgatgtct ggggcgcagg gaccacaatc 420
accgtctcct cagccaaaac gacaccccca tctgtctatc cactggcccc tggatctgct 480
gcccaaacta actccatggt gaccctggga tgcctggtca agggctattt ccctgagcca 540
gtgacagtga cctggaactc tggatccctg tccagcggtg tgcacacctt cccagctgtc 600
ctgcagtctg acctctacac tctgagcagc tcagtgactg tcccctccag cacctggccc 660
agcgagaccg tcacctgcaa cgttgcccac ccggccagca gcaccaaggt ggacaagaaa 720
attgtgccca gggattgtgg ttgtaagcct tgcatatgta cagtcccaga agtatcatct 780
gtcttcatct tccccccaaa gcccaaggat gtgctcacca ttactctgac tcctaaggtc 840
acgtgtgttg tggtagacat cagcaaggat gatcccgagg tccagttcag ctggtttgta 900
gatgatgtgg aggtgcacac agctcagacg caaccccggg aggagcagtt caacagcact 960
ttccgctcag tcagtgaact tcccatcatg caccaggact ggctcaatgg caaggagttc 1020
aaatgcaggg tcaacagtgc agctttccct gcccccatcg agaaaaccat ctccaaaacc 1080
aaaggcagac cgaaggctcc acaggtgtac accattccac ctcccaagga gcagatggcc 1140
aaggataaag tcagtctgac ctgcatgata acagacttct tccctgaaga cattactgtg 1200
gagtggcagt ggaatgggca gccagcggag aactacaaga acactcagcc catcatggac 1260
acagatggct cttacttcat ctacagcaag ctcaatgtgc agaagagcaa ctgggaggca 1320
ggaaatactt tcacctgctc tgtgttacat gagggcctgc acaaccacca tactgagaag 1380
agcctctccc actctcctgg taaatga 1407
<210> 133
<211> 214
<212> PRT
<213> 家鼷鼠
<400> 133
Asp Ile Gln Met Thr Gln Ile Thr Ser Ser Leu Ser Ala Ser Leu Gly
1 5 10 15
Asp Arg Val Ser Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Asn Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Phe Lys Leu Leu Ile
35 40 45
Phe Tyr Thr Ser Arg Leu Leu Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Tyr Asn Leu Glu Gln
65 70 75 80
Glu Asp Phe Ala Thr Tyr Phe Cys Gln Gln Gly Asp Thr Leu Pro Tyr
85 90 95
Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Ala Asp Ala Ala
100 105 110
Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln Leu Thr Ser Gly
115 120 125
Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr Pro Lys Asp Ile
130 135 140
Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln Asn Gly Val Leu
145 150 155 160
Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr Tyr Ser Met Ser
165 170 175
Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg His Asn Ser Tyr
180 185 190
Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro Ile Val Lys Ser
195 200 205
Phe Asn Arg Asn Glu Cys
210
<210> 134
<211> 645
<212> DNA
<213> 家鼷鼠
<400> 134
gatatccaga tgacacagat tacatcctcc ctgtctgcct ctctgggaga cagggtctcc 60
atcagttgca gggcaagtca agacattagc aattatttaa actggtatca gcagaaacca 120
gatggaactt ttaaactcct tatcttctac acatcaagat tactctcagg agtcccatca 180
aggttcagtg gcagtgggtc tggaacagat tattctctca ccatttacaa cctggagcaa 240
gaagattttg ccacttactt ttgccaacag ggagatacgc ttccgtacac tttcggaggg 300
gggaccaagc tggaaataaa acgggctgat gctgcaccaa ctgtatccat cttcccacca 360
tccagtgagc agttaacatc tggaggtgcc tcagtcgtgt gcttcttgaa caacttctac 420
cccaaagaca tcaatgtcaa gtggaagatt gatggcagtg aacgacaaaa tggcgtcctg 480
aacagttgga ctgatcagga cagcaaagac agcacctaca gcatgagcag caccctcacg 540
ttgaccaagg acgagtatga acgacataac agctatacct gtgaggccac tcacaagaca 600
tcaacttcac ccattgtcaa gagcttcaac aggaatgagt gttag 645
<210> 135
<211> 234
<212> PRT
<213> 家鼷鼠
<400> 135
Met Met Ser Ser Ala Gln Phe Leu Gly Leu Leu Leu Leu Cys Phe Gln
1 5 10 15
Gly Thr Arg Cys Asp Ile Gln Met Thr Gln Ile Thr Ser Ser Leu Ser
20 25 30
Ala Ser Leu Gly Asp Arg Val Ser Ile Ser Cys Arg Ala Ser Gln Asp
35 40 45
Ile Ser Asn Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Phe
50 55 60
Lys Leu Leu Ile Phe Tyr Thr Ser Arg Leu Leu Ser Gly Val Pro Ser
65 70 75 80
Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Tyr
85 90 95
Asn Leu Glu Gln Glu Asp Phe Ala Thr Tyr Phe Cys Gln Gln Gly Asp
100 105 110
Thr Leu Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
Ala Asp Ala Ala Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln
130 135 140
Leu Thr Ser Gly Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr
145 150 155 160
Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln
165 170 175
Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr
180 185 190
Tyr Ser Met Ser Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg
195 200 205
His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro
210 215 220
Ile Val Lys Ser Phe Asn Arg Asn Glu Cys
225 230
<210> 136
<211> 705
<212> DNA
<213> 家鼷鼠
<400> 136
atgatgtcct ctgctcagtt ccttggtctc ctgttgctct gttttcaagg taccagatgt 60
gatatccaga tgacacagat tacatcctcc ctgtctgcct ctctgggaga cagggtctcc 120
atcagttgca gggcaagtca agacattagc aattatttaa actggtatca gcagaaacca 180
gatggaactt ttaaactcct tatcttctac acatcaagat tactctcagg agtcccatca 240
aggttcagtg gcagtgggtc tggaacagat tattctctca ccatttacaa cctggagcaa 300
gaagattttg ccacttactt ttgccaacag ggagatacgc ttccgtacac tttcggaggg 360
gggaccaagc tggaaataaa acgggctgat gctgcaccaa ctgtatccat cttcccacca 420
tccagtgagc agttaacatc tggaggtgcc tcagtcgtgt gcttcttgaa caacttctac 480
cccaaagaca tcaatgtcaa gtggaagatt gatggcagtg aacgacaaaa tggcgtcctg 540
aacagttgga ctgatcagga cagcaaagac agcacctaca gcatgagcag caccctcacg 600
ttgaccaagg acgagtatga acgacataac agctatacct gtgaggccac tcacaagaca 660
tcaacttcac ccattgtcaa gagcttcaac aggaatgagt gttag 705
<210> 137
<211> 447
<212> PRT
<213> 家鼷鼠
<400> 137
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Met Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Asn Met His Trp Val Lys Gln Asn Gln Gly Lys Thr Leu Glu Trp Ile
35 40 45
Gly Glu Ile Asn Pro Asn Ser Gly Gly Ala Gly Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Thr Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Leu Gly Tyr Asp Asp Ile Tyr Asp Asp Trp Tyr Phe Asp Val
100 105 110
Trp Gly Ala Gly Thr Thr Val Thr Val Ser Ser Ala Lys Thr Thr Pro
115 120 125
Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr Asn Ser
130 135 140
Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val
145 150 155 160
Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr Phe
165 170 175
Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr
180 185 190
Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val Thr Cys Asn Val Ala
195 200 205
His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val Pro Arg Asp
210 215 220
Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser Ser Val
225 230 235 240
Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr
245 250 255
Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu
260 265 270
Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln
275 280 285
Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser
290 295 300
Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys
305 310 315 320
Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile
325 330 335
Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro
340 345 350
Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met
355 360 365
Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn
370 375 380
Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr
385 390 395 400
Asp Gly Ser Tyr Phe Ile Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn
405 410 415
Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu
420 425 430
His Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys
435 440 445
<210> 138
<211> 1344
<212> DNA
<213> 家鼷鼠
<400> 138
gaggtccaac tgcaacagtc tggacctgaa ctaatgaagc ctggggcttc agtgaagatg 60
tcctgcaagg cttctggata tacattcact gactacaaca tgcactgggt gaagcagaac 120
caaggaaaga ccctagagtg gataggagaa attaatccta acagtggtgg tgctggctac 180
aaccagaagt tcaagggcaa ggccacattg actgtagaca agtcctccac cacagcctac 240
atggagctcc gcagcctgac atctgaggac tctgcagtct attactgtgc aagattgggc 300
tacgatgata tctacgacga ctggtacttc gatgtctggg gcgcagggac cacggtcacc 360
gtctcctcag ccaaaacgac acccccatct gtctatccac tggcccctgg atctgctgcc 420
caaactaact ccatggtgac cctgggatgc ctggtcaagg gctatttccc tgagccagtg 480
acagtgacct ggaactctgg atccctgtcc agcggtgtgc acaccttccc agctgtcctg 540
cagtctgacc tctacactct gagcagctca gtgactgtcc cctccagcac ctggcccagc 600
gagaccgtca cctgcaacgt tgcccacccg gccagcagca ccaaggtgga caagaaaatt 660
gtgcccaggg attgtggttg taagccttgc atatgtacag tcccagaagt atcatctgtc 720
ttcatcttcc ccccaaagcc caaggatgtg ctcaccatta ctctgactcc taaggtcacg 780
tgtgttgtgg tagacatcag caaggatgat cccgaggtcc agttcagctg gtttgtagat 840
gatgtggagg tgcacacagc tcagacgcaa ccccgggagg agcagttcaa cagcactttc 900
cgctcagtca gtgaacttcc catcatgcac caggactggc tcaatggcaa ggagttcaaa 960
tgcagggtca acagtgcagc tttccctgcc cccatcgaga aaaccatctc caaaaccaaa 1020
ggcagaccga aggctccaca ggtgtacacc attccacctc ccaaggagca gatggccaag 1080
gataaagtca gtctgacctg catgataaca gacttcttcc ctgaagacat tactgtggag 1140
tggcagtgga atgggcagcc agcggagaac tacaagaaca ctcagcccat catggacaca 1200
gatggctctt acttcatcta cagcaagctc aatgtgcaga agagcaactg ggaggcagga 1260
aatactttca cctgctctgt gttacatgag ggcctgcaca accaccatac tgagaagagc 1320
ctctcccact ctcctggtaa atga 1344
<210> 139
<211> 466
<212> PRT
<213> 家鼷鼠
<400> 139
Met Gly Trp Ser Trp Thr Phe Leu Phe Leu Leu Ser Gly Thr Ala Gly
1 5 10 15
Val Leu Ser Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Met Lys
20 25 30
Pro Gly Ala Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe
35 40 45
Thr Asp Tyr Asn Met His Trp Val Lys Gln Asn Gln Gly Lys Thr Leu
50 55 60
Glu Trp Ile Gly Glu Ile Asn Pro Asn Ser Gly Gly Ala Gly Tyr Asn
65 70 75 80
Gln Lys Phe Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Thr
85 90 95
Thr Ala Tyr Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Leu Gly Tyr Asp Asp Ile Tyr Asp Asp Trp Tyr
115 120 125
Phe Asp Val Trp Gly Ala Gly Thr Thr Val Thr Val Ser Ser Ala Lys
130 135 140
Thr Thr Pro Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln
145 150 155 160
Thr Asn Ser Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro
165 170 175
Glu Pro Val Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val
180 185 190
His Thr Phe Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser
195 200 205
Ser Val Thr Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val Thr Cys
210 215 220
Asn Val Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val
225 230 235 240
Pro Arg Asp Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val
245 250 255
Ser Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile
260 265 270
Thr Leu Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp
275 280 285
Asp Pro Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His
290 295 300
Thr Ala Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg
305 310 315 320
Ser Val Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys
325 330 335
Glu Phe Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu
340 345 350
Lys Thr Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr
355 360 365
Thr Ile Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu
370 375 380
Thr Cys Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp
385 390 395 400
Gln Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile
405 410 415
Met Asp Thr Asp Gly Ser Tyr Phe Ile Tyr Ser Lys Leu Asn Val Gln
420 425 430
Lys Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His
435 440 445
Glu Gly Leu His Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro
450 455 460
Gly Lys
465
<210> 140
<211> 1401
<212> DNA
<213> 家鼷鼠
<400> 140
atgggatgga gctggacctt tctcttcctc ctgtcaggaa ctgcaggtgt cctctctgag 60
gtccaactgc aacagtctgg acctgaacta atgaagcctg gggcttcagt gaagatgtcc 120
tgcaaggctt ctggatatac attcactgac tacaacatgc actgggtgaa gcagaaccaa 180
ggaaagaccc tagagtggat aggagaaatt aatcctaaca gtggtggtgc tggctacaac 240
cagaagttca agggcaaggc cacattgact gtagacaagt cctccaccac agcctacatg 300
gagctccgca gcctgacatc tgaggactct gcagtctatt actgtgcaag attgggctac 360
gatgatatct acgacgactg gtacttcgat gtctggggcg cagggaccac ggtcaccgtc 420
tcctcagcca aaacgacacc cccatctgtc tatccactgg cccctggatc tgctgcccaa 480
actaactcca tggtgaccct gggatgcctg gtcaagggct atttccctga gccagtgaca 540
gtgacctgga actctggatc cctgtccagc ggtgtgcaca ccttcccagc tgtcctgcag 600
tctgacctct acactctgag cagctcagtg actgtcccct ccagcacctg gcccagcgag 660
accgtcacct gcaacgttgc ccacccggcc agcagcacca aggtggacaa gaaaattgtg 720
cccagggatt gtggttgtaa gccttgcata tgtacagtcc cagaagtatc atctgtcttc 780
atcttccccc caaagcccaa ggatgtgctc accattactc tgactcctaa ggtcacgtgt 840
gttgtggtag acatcagcaa ggatgatccc gaggtccagt tcagctggtt tgtagatgat 900
gtggaggtgc acacagctca gacgcaaccc cgggaggagc agttcaacag cactttccgc 960
tcagtcagtg aacttcccat catgcaccag gactggctca atggcaagga gttcaaatgc 1020
agggtcaaca gtgcagcttt ccctgccccc atcgagaaaa ccatctccaa aaccaaaggc 1080
agaccgaagg ctccacaggt gtacaccatt ccacctccca aggagcagat ggccaaggat 1140
aaagtcagtc tgacctgcat gataacagac ttcttccctg aagacattac tgtggagtgg 1200
cagtggaatg ggcagccagc ggagaactac aagaacactc agcccatcat ggacacagat 1260
ggctcttact tcatctacag caagctcaat gtgcagaaga gcaactggga ggcaggaaat 1320
actttcacct gctctgtgtt acatgagggc ctgcacaacc accatactga gaagagcctc 1380
tcccactctc ctggtaaatg a 1401
<210> 141
<211> 214
<212> PRT
<213> 人工序列
<220>
<223> 合成多肽
<220>
<221> MISC_FEATURE
<223> 人源化抗体序列
<400> 141
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Ser Asn Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Tyr Thr Ser Arg Leu Leu Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Asp Thr Leu Pro Tyr
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala
100 105 110
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly
115 120 125
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala
130 135 140
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
180 185 190
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser
195 200 205
Phe Asn Arg Gly Glu Cys
210
<210> 142
<211> 642
<212> DNA
<213> 人工序列
<220>
<223> 合成多核苷酸
<220>
<221> misc_feature
<223> 人源化抗体序列
<400> 142
gacatccaga tgacccagtc tccatcctcc ctctccgcat ccgtaggcga ccgcgtaacc 60
ataacatgta gagcatctca agatatttcc aactatttga attggtacca acaaaaaccc 120
ggcaaagcac ctaaactcct catttactat acatcaagac tcctctccgg cgttccatca 180
cgattctcag gctccggctc cggcacagat ttcacactca ctatttcctc cctccaacca 240
gaagattttg caacctatta ctgtcaacaa ggcgatacac tcccatacac attcggcggc 300
ggcacaaaag ttgaaattaa acgtacggtg gctgcaccat ctgtcttcat cttcccgcca 360
tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 420
cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 480
gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 540
ctgagcaaag cagactacga gaaacacaaa gtctacgcct gcgaagtcac ccatcagggc 600
ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gt 642
<210> 143
<211> 236
<212> PRT
<213> 人工序列
<220>
<223> 合成多肽
<220>
<221> MISC_FEATURE
<223> 人源化抗体序列
<400> 143
Met Asp Met Arg Val Pro Ala Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Arg Gly Ala Arg Cys Asp Ile Gln Met Thr Gln Ser Pro Ser Ser
20 25 30
Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser
35 40 45
Gln Asp Ile Ser Asn Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys
50 55 60
Ala Pro Lys Leu Leu Ile Tyr Tyr Thr Ser Arg Leu Leu Ser Gly Val
65 70 75 80
Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
85 90 95
Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln
100 105 110
Gly Asp Thr Leu Pro Tyr Thr Phe Gly Gly Gly Thr Lys Val Glu Ile
115 120 125
Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp
130 135 140
Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn
145 150 155 160
Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu
165 170 175
Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp
180 185 190
Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr
195 200 205
Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser
210 215 220
Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
225 230 235
<210> 144
<211> 708
<212> DNA
<213> 人工序列
<220>
<223> 合成多核苷酸
<220>
<221> misc_feature
<223> 人源化抗体序列
<400> 144
atggacatga gggtccccgc tcagctcctg gggctcctgc tactctggct ccgaggtgcc 60
agatgtgaca tccagatgac ccagtctcca tcctccctct ccgcatccgt aggcgaccgc 120
gtaaccataa catgtagagc atctcaagat atttccaact atttgaattg gtaccaacaa 180
aaacccggca aagcacctaa actcctcatt tactatacat caagactcct ctccggcgtt 240
ccatcacgat tctcaggctc cggctccggc acagatttca cactcactat ttcctccctc 300
caaccagaag attttgcaac ctattactgt caacaaggcg atacactccc atacacattc 360
ggcggcggca caaaagttga aattaaacgt acggtggctg caccatctgt cttcatcttc 420
ccgccatctg atgagcagtt gaaatctgga actgcctctg ttgtgtgcct gctgaataac 480
ttctatccca gagaggccaa agtacagtgg aaggtggata acgccctcca atcgggtaac 540
tcccaggaga gtgtcacaga gcaggacagc aaggacagca cctacagcct cagcagcacc 600
ctgacgctga gcaaagcaga ctacgagaaa cacaaagtct acgcctgcga agtcacccat 660
cagggcctga gctcgcccgt cacaaagagc ttcaacaggg gagagtgt 708
<210> 145
<211> 449
<212> PRT
<213> 人工序列
<220>
<223> 合成多肽
<220>
<221> MISC_FEATURE
<223> 人源化抗体序列
<400> 145
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Asn Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Glu Ile Asn Pro Asn Ser Gly Gly Ala Gly Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Leu Gly Tyr Asp Asp Ile Tyr Asp Asp Trp Tyr Phe Asp Val
100 105 110
Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly
115 120 125
Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser
130 135 140
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
145 150 155 160
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
165 170 175
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
180 185 190
Thr Val Pro Ser Ser Asn Phe Gly Thr Gln Thr Tyr Thr Cys Asn Val
195 200 205
Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Thr Val Glu Arg Lys
210 215 220
Cys Cys Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro
225 230 235 240
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
245 250 255
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
260 265 270
Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
275 280 285
Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Val
290 295 300
Val Ser Val Leu Thr Val Val His Gln Asp Trp Leu Asn Gly Lys Glu
305 310 315 320
Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu Lys
325 330 335
Thr Ile Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr
340 345 350
Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr
355 360 365
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu
370 375 380
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Met Leu
385 390 395 400
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys
405 410 415
Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu
420 425 430
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
435 440 445
Lys
<210> 146
<211> 1347
<212> DNA
<213> 人工序列
<220>
<223> 合成多核苷酸
<220>
<221> misc_feature
<223> 人源化抗体序列
<400> 146
gaggtgcagc tggtgcagag cggcgccgag gtaaaaaaac caggagcaag cgttaaagtt 60
tcttgtaaag caagcggata tacatttaca gattacaaca tgcattgggt aagacaagcg 120
ccaggacaag gattggaatg gatgggcgaa attaacccta atagtggagg agcaggctac 180
aatcaaaaat tcaaagggag agttacaatg acaacagaca caagcacttc aacagcatat 240
atggaactgc gatcacttag aagcgacgat acagctgtat actattgcgc acgacttggg 300
tatgatgata tatatgatga ctggtatttc gatgtttggg gccagggaac aacagttacc 360
gtctctagtg cctccaccaa gggcccatcg gtcttccccc tggcgccctg ctccaggagc 420
acctccgaga gcacagcggc cctgggctgc ctggtcaagg actacttccc cgaaccggtg 480
acggtgtcgt ggaactcagg cgctctgacc agcggcgtgc acaccttccc agctgtccta 540
cagtcctcag gactctactc cctcagcagc gtggtgaccg tgccctccag caacttcggc 600
acccagacct acacctgcaa cgtagatcac aagcccagca acaccaaggt ggacaagaca 660
gttgagcgca aatgttgtgt cgagtgccca ccgtgcccag caccacctgt ggcaggaccg 720
tcagtcttcc tcttcccccc aaaacccaag gacaccctca tgatctcccg gacccctgag 780
gtcacgtgcg tggtggtgga cgtgagccac gaagaccccg aggtccagtt caactggtac 840
gtggacggcg tggaggtgca taatgccaag acaaagccac gggaggagca gttcaacagc 900
acgttccgtg tggtcagcgt cctcaccgtt gtgcaccagg actggctgaa cggcaaggag 960
tacaagtgca aggtctccaa caaaggcctc ccagccccca tcgagaaaac catctccaaa 1020
accaaagggc agccccgaga accacaggtg tacaccctgc ccccatcccg ggaggagatg 1080
accaagaacc aggtcagcct gacctgcctg gtcaaaggct tctaccccag cgacatcgcc 1140
gtggagtggg agagcaatgg gcagccggag aacaactaca agaccacacc tcccatgctg 1200
gactccgacg gctccttctt cctctacagc aagctcaccg tggacaagag caggtggcag 1260
caggggaacg tcttctcatg ctccgtgatg catgaggctc tgcacaacca ctacacgcag 1320
aagagcctct ccctgtctcc gggtaaa 1347
<210> 147
<211> 468
<212> PRT
<213> 人工序列
<220>
<223> 合成多肽
<220>
<221> MISC_FEATURE
<223> 人源化抗体序列
<400> 147
Met Asp Trp Thr Trp Arg Ile Leu Phe Leu Val Ala Ala Ala Thr Gly
1 5 10 15
Ala His Ser Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys
20 25 30
Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe
35 40 45
Thr Asp Tyr Asn Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu
50 55 60
Glu Trp Met Gly Glu Ile Asn Pro Asn Ser Gly Gly Ala Gly Tyr Asn
65 70 75 80
Gln Lys Phe Lys Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser
85 90 95
Thr Ala Tyr Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Leu Gly Tyr Asp Asp Ile Tyr Asp Asp Trp Tyr
115 120 125
Phe Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ser
130 135 140
Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr
145 150 155 160
Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro
165 170 175
Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val
180 185 190
His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser
195 200 205
Ser Val Val Thr Val Pro Ser Ser Asn Phe Gly Thr Gln Thr Tyr Thr
210 215 220
Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Thr Val
225 230 235 240
Glu Arg Lys Cys Cys Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val
245 250 255
Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
260 265 270
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
275 280 285
His Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu
290 295 300
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr
305 310 315 320
Phe Arg Val Val Ser Val Leu Thr Val Val His Gln Asp Trp Leu Asn
325 330 335
Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ala Pro
340 345 350
Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln
355 360 365
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
370 375 380
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
385 390 395 400
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
405 410 415
Pro Met Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
420 425 430
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
435 440 445
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
450 455 460
Ser Pro Gly Lys
465
<210> 148
<211> 1404
<212> DNA
<213> 家鼷鼠
<400> 148
atggactgga cctggaggat cctcttcttg gtggcagcag ccacaggagc ccactccgag 60
gtgcagctgg tgcagagcgg cgccgaggta aaaaaaccag gagcaagcgt taaagtttct 120
tgtaaagcaa gcggatatac atttacagat tacaacatgc attgggtaag acaagcgcca 180
ggacaaggat tggaatggat gggcgaaatt aaccctaata gtggaggagc aggctacaat 240
caaaaattca aagggagagt tacaatgaca acagacacaa gcacttcaac agcatatatg 300
gaactgcgat cacttagaag cgacgataca gctgtatact attgcgcacg acttgggtat 360
gatgatatat atgatgactg gtatttcgat gtttggggcc agggaacaac agttaccgtc 420
tctagtgcct ccaccaaggg cccatcggtc ttccccctgg cgccctgctc caggagcacc 480
tccgagagca cagcggccct gggctgcctg gtcaaggact acttccccga accggtgacg 540
gtgtcgtgga actcaggcgc tctgaccagc ggcgtgcaca ccttcccagc tgtcctacag 600
tcctcaggac tctactccct cagcagcgtg gtgaccgtgc cctccagcaa cttcggcacc 660
cagacctaca cctgcaacgt agatcacaag cccagcaaca ccaaggtgga caagacagtt 720
gagcgcaaat gttgtgtcga gtgcccaccg tgcccagcac cacctgtggc aggaccgtca 780
gtcttcctct tccccccaaa acccaaggac accctcatga tctcccggac ccctgaggtc 840
acgtgcgtgg tggtggacgt gagccacgaa gaccccgagg tccagttcaa ctggtacgtg 900
gacggcgtgg aggtgcataa tgccaagaca aagccacggg aggagcagtt caacagcacg 960
ttccgtgtgg tcagcgtcct caccgttgtg caccaggact ggctgaacgg caaggagtac 1020
aagtgcaagg tctccaacaa aggcctccca gcccccatcg agaaaaccat ctccaaaacc 1080
aaagggcagc cccgagaacc acaggtgtac accctgcccc catcccggga ggagatgacc 1140
aagaaccagg tcagcctgac ctgcctggtc aaaggcttct accccagcga catcgccgtg 1200
gagtgggaga gcaatgggca gccggagaac aactacaaga ccacacctcc catgctggac 1260
tccgacggct ccttcttcct ctacagcaag ctcaccgtgg acaagagcag gtggcagcag 1320
gggaacgtct tctcatgctc cgtgatgcat gaggctctgc acaaccacta cacgcagaag 1380
agcctctccc tgtctccggg taaa 1404
<210> 149
<211> 214
<212> PRT
<213> 家鼷鼠
<400> 149
Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser Ala Ser Leu Gly
1 5 10 15
Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Asn Tyr
20 25 30
Leu Asn Trp Phe Gln Gln Lys Pro Asp Gly Thr Leu Lys Leu Leu Ile
35 40 45
Phe Tyr Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Ser Asn Leu Glu Gln
65 70 75 80
Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Gly Asp Thr Leu Pro Tyr
85 90 95
Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Arg Arg Ala Asp Ala Ala
100 105 110
Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln Leu Thr Ser Gly
115 120 125
Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr Pro Lys Asp Ile
130 135 140
Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln Asn Gly Val Leu
145 150 155 160
Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr Tyr Ser Met Ser
165 170 175
Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg His Asn Ser Tyr
180 185 190
Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro Ile Val Lys Ser
195 200 205
Phe Asn Arg Asn Glu Cys
210
<210> 150
<211> 645
<212> DNA
<213> 家鼷鼠
<400> 150
gatatccaga tgacacagac tacatcctcc ctgtctgcct ctctgggaga cagagtcacc 60
atcagttgca gggcaagtca ggacattagc aattatttaa actggtttca gcagaaacca 120
gatggaactc ttaaactcct gatcttctac acatcaagat tacactcagg agttccatca 180
aggttcagtg gcagtgggtc tggaacagat tattctctca ccattagcaa cctggagcaa 240
gaagatattg ccacttactt ttgccaacag ggtgatacgc ttccgtacac gttcgggggg 300
gggaccaagc tggaaataag acgggctgat gctgcaccaa ctgtatccat cttcccacca 360
tccagtgagc agttaacatc tggaggtgcc tcagtcgtgt gcttcttgaa caacttctac 420
cccaaagaca tcaatgtcaa gtggaagatt gatggcagtg aacgacaaaa tggcgtcctg 480
aacagttgga ctgatcagga cagcaaagac agcacctaca gcatgagcag caccctcacg 540
ttgaccaagg acgagtatga acgacataac agctatacct gtgaggccac tcacaagaca 600
tcaacttcac ccattgtcaa gagcttcaac aggaatgagt gttag 645
<210> 151
<211> 234
<212> PRT
<213> 家鼷鼠
<400> 151
Met Met Ser Ser Ala Gln Phe Leu Gly Leu Leu Leu Leu Cys Phe Gln
1 5 10 15
Gly Thr Arg Cys Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser
20 25 30
Ala Ser Leu Gly Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln Asp
35 40 45
Ile Ser Asn Tyr Leu Asn Trp Phe Gln Gln Lys Pro Asp Gly Thr Leu
50 55 60
Lys Leu Leu Ile Phe Tyr Thr Ser Arg Leu His Ser Gly Val Pro Ser
65 70 75 80
Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Ser
85 90 95
Asn Leu Glu Gln Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Gly Asp
100 105 110
Thr Leu Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Arg Arg
115 120 125
Ala Asp Ala Ala Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln
130 135 140
Leu Thr Ser Gly Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr
145 150 155 160
Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln
165 170 175
Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr
180 185 190
Tyr Ser Met Ser Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg
195 200 205
His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro
210 215 220
Ile Val Lys Ser Phe Asn Arg Asn Glu Cys
225 230
<210> 152
<211> 705
<212> DNA
<213> 家鼷鼠
<400> 152
atgatgtcct ctgctcagtt ccttggtctc ctgttgctct gttttcaagg taccagatgt 60
gatatccaga tgacacagac tacatcctcc ctgtctgcct ctctgggaga cagagtcacc 120
atcagttgca gggcaagtca ggacattagc aattatttaa actggtttca gcagaaacca 180
gatggaactc ttaaactcct gatcttctac acatcaagat tacactcagg agttccatca 240
aggttcagtg gcagtgggtc tggaacagat tattctctca ccattagcaa cctggagcaa 300
gaagatattg ccacttactt ttgccaacag ggtgatacgc ttccgtacac gttcgggggg 360
gggaccaagc tggaaataag acgggctgat gctgcaccaa ctgtatccat cttcccacca 420
tccagtgagc agttaacatc tggaggtgcc tcagtcgtgt gcttcttgaa caacttctac 480
cccaaagaca tcaatgtcaa gtggaagatt gatggcagtg aacgacaaaa tggcgtcctg 540
aacagttgga ctgatcagga cagcaaagac agcacctaca gcatgagcag caccctcacg 600
ttgaccaagg acgagtatga acgacataac agctatacct gtgaggccac tcacaagaca 660
tcaacttcac ccattgtcaa gagcttcaac aggaatgagt gttag 705
<210> 153
<211> 447
<212> PRT
<213> 家鼷鼠
<400> 153
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Met Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Asn Met His Trp Val Lys Gln Asn Gln Gly Lys Ser Leu Glu Trp Ile
35 40 45
Gly Glu Ile Asn Pro Asn Ser Gly Gly Ser Gly Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Leu Val Tyr Asp Gly Ser Tyr Glu Asp Trp Tyr Phe Asp Val
100 105 110
Trp Gly Ala Gly Thr Thr Val Thr Val Ser Ser Ala Lys Thr Thr Pro
115 120 125
Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr Asn Ser
130 135 140
Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val
145 150 155 160
Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr Phe
165 170 175
Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr
180 185 190
Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val Thr Cys Asn Val Ala
195 200 205
His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val Pro Arg Asp
210 215 220
Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser Ser Val
225 230 235 240
Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr
245 250 255
Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu
260 265 270
Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln
275 280 285
Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser
290 295 300
Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys
305 310 315 320
Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile
325 330 335
Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro
340 345 350
Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met
355 360 365
Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn
370 375 380
Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr
385 390 395 400
Asp Gly Ser Tyr Phe Ile Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn
405 410 415
Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu
420 425 430
His Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys
435 440 445
<210> 154
<211> 1344
<212> DNA
<213> 家鼷鼠
<400> 154
gaggtccagc tgcaacagtc tggacctgaa ctaatgaagc ctggggcttc agtgaagatg 60
tcctgcaagg cttctggata cacattcact gactacaaca tgcactgggt gaaacagaac 120
caaggaaaga gcctagagtg gataggagaa attaatccta acagtggtgg tagtggctac 180
aaccaaaagt tcaaaggcaa ggccacattg actgtagaca agtcttccag cacagcctac 240
atggagctcc gcagcctgac atctgaggac tctgcagtct attactgtgc aagattggtc 300
tacgatggca gctacgagga ctggtacttc gatgtctggg gcgcagggac cacggtcacc 360
gtctcctcag ccaaaacgac acccccatct gtctatccac tggcccctgg atctgctgcc 420
caaactaact ccatggtgac cctgggatgc ctggtcaagg gctatttccc tgagccagtg 480
acagtgacct ggaactctgg atccctgtcc agcggtgtgc acaccttccc agctgtcctg 540
cagtctgacc tctacactct gagcagctca gtgactgtcc cctccagcac ctggcccagc 600
gagaccgtca cctgcaacgt tgcccacccg gccagcagca ccaaggtgga caagaaaatt 660
gtgcccaggg attgtggttg taagccttgc atatgtacag tcccagaagt atcatctgtc 720
ttcatcttcc ccccaaagcc caaggatgtg ctcaccatta ctctgactcc taaggtcacg 780
tgtgttgtgg tagacatcag caaggatgat cccgaggtcc agttcagctg gtttgtagat 840
gatgtggagg tgcacacagc tcagacgcaa ccccgggagg agcagttcaa cagcactttc 900
cgctcagtca gtgaacttcc catcatgcac caggactggc tcaatggcaa ggagttcaaa 960
tgcagggtca acagtgcagc tttccctgcc cccatcgaga aaaccatctc caaaaccaaa 1020
ggcagaccga aggctccaca ggtgtacacc attccacctc ccaaggagca gatggccaag 1080
gataaagtca gtctgacctg catgataaca gacttcttcc ctgaagacat tactgtggag 1140
tggcagtgga atgggcagcc agcggagaac tacaagaaca ctcagcccat catggacaca 1200
gatggctctt acttcatcta cagcaagctc aatgtgcaga agagcaactg ggaggcagga 1260
aatactttca cctgctctgt gttacatgag ggcctgcaca accaccatac tgagaagagc 1320
ctctcccact ctcctggtaa atga 1344
<210> 155
<211> 466
<212> PRT
<213> 家鼷鼠
<400> 155
Met Gly Trp Ser Trp Thr Phe Leu Phe Leu Leu Ser Gly Thr Ala Gly
1 5 10 15
Val Leu Ser Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Met Lys
20 25 30
Pro Gly Ala Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe
35 40 45
Thr Asp Tyr Asn Met His Trp Val Lys Gln Asn Gln Gly Lys Ser Leu
50 55 60
Glu Trp Ile Gly Glu Ile Asn Pro Asn Ser Gly Gly Ser Gly 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 Ser Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Leu Val Tyr Asp Gly Ser Tyr Glu Asp Trp Tyr
115 120 125
Phe Asp Val Trp Gly Ala Gly Thr Thr Val Thr Val Ser Ser Ala Lys
130 135 140
Thr Thr Pro Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln
145 150 155 160
Thr Asn Ser Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro
165 170 175
Glu Pro Val Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val
180 185 190
His Thr Phe Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser
195 200 205
Ser Val Thr Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val Thr Cys
210 215 220
Asn Val Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val
225 230 235 240
Pro Arg Asp Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val
245 250 255
Ser Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile
260 265 270
Thr Leu Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp
275 280 285
Asp Pro Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His
290 295 300
Thr Ala Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg
305 310 315 320
Ser Val Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys
325 330 335
Glu Phe Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu
340 345 350
Lys Thr Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr
355 360 365
Thr Ile Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu
370 375 380
Thr Cys Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp
385 390 395 400
Gln Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile
405 410 415
Met Asp Thr Asp Gly Ser Tyr Phe Ile Tyr Ser Lys Leu Asn Val Gln
420 425 430
Lys Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His
435 440 445
Glu Gly Leu His Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro
450 455 460
Gly Lys
465
<210> 156
<211> 1401
<212> DNA
<213> 家鼷鼠
<400> 156
atgggatgga gctggacctt tctcttcctc ctgtcaggaa ctgcaggtgt cctctctgag 60
gtccagctgc aacagtctgg acctgaacta atgaagcctg gggcttcagt gaagatgtcc 120
tgcaaggctt ctggatacac attcactgac tacaacatgc actgggtgaa acagaaccaa 180
ggaaagagcc tagagtggat aggagaaatt aatcctaaca gtggtggtag tggctacaac 240
caaaagttca aaggcaaggc cacattgact gtagacaagt cttccagcac agcctacatg 300
gagctccgca gcctgacatc tgaggactct gcagtctatt actgtgcaag attggtctac 360
gatggcagct acgaggactg gtacttcgat gtctggggcg cagggaccac ggtcaccgtc 420
tcctcagcca aaacgacacc cccatctgtc tatccactgg cccctggatc tgctgcccaa 480
actaactcca tggtgaccct gggatgcctg gtcaagggct atttccctga gccagtgaca 540
gtgacctgga actctggatc cctgtccagc ggtgtgcaca ccttcccagc tgtcctgcag 600
tctgacctct acactctgag cagctcagtg actgtcccct ccagcacctg gcccagcgag 660
accgtcacct gcaacgttgc ccacccggcc agcagcacca aggtggacaa gaaaattgtg 720
cccagggatt gtggttgtaa gccttgcata tgtacagtcc cagaagtatc atctgtcttc 780
atcttccccc caaagcccaa ggatgtgctc accattactc tgactcctaa ggtcacgtgt 840
gttgtggtag acatcagcaa ggatgatccc gaggtccagt tcagctggtt tgtagatgat 900
gtggaggtgc acacagctca gacgcaaccc cgggaggagc agttcaacag cactttccgc 960
tcagtcagtg aacttcccat catgcaccag gactggctca atggcaagga gttcaaatgc 1020
agggtcaaca gtgcagcttt ccctgccccc atcgagaaaa ccatctccaa aaccaaaggc 1080
agaccgaagg ctccacaggt gtacaccatt ccacctccca aggagcagat ggccaaggat 1140
aaagtcagtc tgacctgcat gataacagac ttcttccctg aagacattac tgtggagtgg 1200
cagtggaatg ggcagccagc ggagaactac aagaacactc agcccatcat ggacacagat 1260
ggctcttact tcatctacag caagctcaat gtgcagaaga gcaactggga ggcaggaaat 1320
actttcacct gctctgtgtt acatgagggc ctgcacaacc accatactga gaagagcctc 1380
tcccactctc ctggtaaatg a 1401
<210> 157
<211> 214
<212> PRT
<213> 家鼷鼠
<400> 157
Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser Ala Ser Leu Gly
1 5 10 15
Asp Arg Val Thr Ile Cys Cys Arg Ala Ser Gln Val Ile Thr Asn Tyr
20 25 30
Leu Tyr Trp Tyr Gln Gln Lys Pro Asp Gly Thr Phe Lys Leu Leu Ile
35 40 45
Tyr Tyr Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Ser Asn Leu Glu Gln
65 70 75 80
Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Gly Asp Thr Leu Pro Tyr
85 90 95
Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Ala Asp Ala Ala
100 105 110
Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln Leu Thr Ser Gly
115 120 125
Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr Pro Lys Asp Ile
130 135 140
Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln Asn Gly Val Leu
145 150 155 160
Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr Tyr Ser Met Ser
165 170 175
Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg His Asn Ser Tyr
180 185 190
Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro Ile Val Lys Ser
195 200 205
Phe Asn Arg Asn Glu Cys
210
<210> 158
<211> 642
<212> DNA
<213> 家鼷鼠
<400> 158
gatatccaga tgacacagac tacatcctcc ctgtctgcct ctctgggaga cagagtcacc 60
atctgttgca gggcaagtca ggtcattacc aattatttat actggtatca gcagaaacca 120
gatggaactt ttaaactcct gatctactac acatcaagat tacactcagg agtcccatca 180
aggttcagtg gcagtgggtc tggaacagat tattctctca ccattagcaa cctggaacag 240
gaagatattg ccacttactt ttgccaacag ggtgatacgc ttccgtacac gttcggaggg 300
gggaccaagc tggaaataaa acgggctgat gctgcaccaa ctgtatccat cttcccacca 360
tccagtgagc agttaacatc tggaggtgcc tcagtcgtgt gcttcttgaa caacttctac 420
cccaaagaca tcaatgtcaa gtggaagatt gatggcagtg aacgacaaaa tggcgtcctg 480
aacagttgga ctgatcagga cagcaaagac agcacctaca gcatgagcag caccctcacg 540
ttgaccaagg acgagtatga acgacataac agctatacct gtgaggccac tcacaagaca 600
tcaacttcac ccattgtcaa gagcttcaac aggaatgagt gt 642
<210> 159
<211> 234
<212> PRT
<213> 家鼷鼠
<400> 159
Met Met Ser Ser Ala Gln Phe Leu Gly Leu Leu Leu Leu Cys Phe Gln
1 5 10 15
Gly Thr Arg Cys Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser
20 25 30
Ala Ser Leu Gly Asp Arg Val Thr Ile Cys Cys Arg Ala Ser Gln Val
35 40 45
Ile Thr Asn Tyr Leu Tyr Trp Tyr Gln Gln Lys Pro Asp Gly Thr Phe
50 55 60
Lys Leu Leu Ile Tyr Tyr Thr Ser Arg Leu His Ser Gly Val Pro Ser
65 70 75 80
Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Ser
85 90 95
Asn Leu Glu Gln Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Gly Asp
100 105 110
Thr Leu Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
Ala Asp Ala Ala Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln
130 135 140
Leu Thr Ser Gly Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr
145 150 155 160
Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln
165 170 175
Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr
180 185 190
Tyr Ser Met Ser Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg
195 200 205
His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro
210 215 220
Ile Val Lys Ser Phe Asn Arg Asn Glu Cys
225 230
<210> 160
<211> 702
<212> DNA
<213> 家鼷鼠
<400> 160
atgatgtcct ctgctcagtt ccttggtctc ctgttgctct gttttcaagg taccagatgt 60
gatatccaga tgacacagac tacatcctcc ctgtctgcct ctctgggaga cagagtcacc 120
atctgttgca gggcaagtca ggtcattacc aattatttat actggtatca gcagaaacca 180
gatggaactt ttaaactcct gatctactac acatcaagat tacactcagg agtcccatca 240
aggttcagtg gcagtgggtc tggaacagat tattctctca ccattagcaa cctggaacag 300
gaagatattg ccacttactt ttgccaacag ggtgatacgc ttccgtacac gttcggaggg 360
gggaccaagc tggaaataaa acgggctgat gctgcaccaa ctgtatccat cttcccacca 420
tccagtgagc agttaacatc tggaggtgcc tcagtcgtgt gcttcttgaa caacttctac 480
cccaaagaca tcaatgtcaa gtggaagatt gatggcagtg aacgacaaaa tggcgtcctg 540
aacagttgga ctgatcagga cagcaaagac agcacctaca gcatgagcag caccctcacg 600
ttgaccaagg acgagtatga acgacataac agctatacct gtgaggccac tcacaagaca 660
tcaacttcac ccattgtcaa gagcttcaac aggaatgagt gt 702
<210> 161
<211> 447
<212> PRT
<213> 家鼷鼠
<400> 161
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Met Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Asn Met His Trp Met Lys Gln Asn Gln Gly Lys Ser Leu Glu Trp Ile
35 40 45
Gly Glu Ile Asn Pro Asn Ser Gly Gly Ala Gly Tyr Asn Gln Gln Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Arg Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Leu Gly Tyr Val Gly Asn Tyr Glu Asp Trp Tyr Phe Asp Val
100 105 110
Trp Gly Ala Gly Thr Thr Val Thr Val Ser Ser Ala Lys Thr Thr Pro
115 120 125
Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr Asn Ser
130 135 140
Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val
145 150 155 160
Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr Phe
165 170 175
Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr
180 185 190
Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val Thr Cys Asn Val Ala
195 200 205
His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val Pro Arg Asp
210 215 220
Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser Ser Val
225 230 235 240
Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr
245 250 255
Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu
260 265 270
Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln
275 280 285
Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser
290 295 300
Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys
305 310 315 320
Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile
325 330 335
Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro
340 345 350
Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met
355 360 365
Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn
370 375 380
Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr
385 390 395 400
Asp Gly Ser Tyr Phe Ile Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn
405 410 415
Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu
420 425 430
His Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys
435 440 445
<210> 162
<211> 1341
<212> DNA
<213> 家鼷鼠
<400> 162
gaggtccagc tgcaacagtc tggacctgaa ctaatgaagc ctggggcttc agtgaagatg 60
tcctgcaagg cttctggata cacattcact gactacaaca tgcactggat gaagcagaac 120
caaggaaaga gcctagaatg gataggagaa attaatccta acagtggtgg tgctggctac 180
aaccagcagt tcaaaggcaa ggccacattg actgtagaca agtcctccag gacagcctac 240
atggagctcc gcagcctgac atctgaggac tctgcagtct attactgtgc aagattgggc 300
tacgttggta attacgagga ctggtacttc gatgtctggg gcgcagggac cacggtcacc 360
gtctcctcag ccaaaacgac acccccatct gtctatccac tggcccctgg atctgctgcc 420
caaactaact ccatggtgac cctgggatgc ctggtcaagg gctatttccc tgagccagtg 480
acagtgacct ggaactctgg atccctgtcc agcggtgtgc acaccttccc agctgtcctg 540
cagtctgacc tctacactct gagcagctca gtgactgtcc cctccagcac ctggcccagc 600
gagaccgtca cctgcaacgt tgcccacccg gccagcagca ccaaggtgga caagaaaatt 660
gtgcccaggg attgtggttg taagccttgc atatgtacag tcccagaagt atcatctgtc 720
ttcatcttcc ccccaaagcc caaggatgtg ctcaccatta ctctgactcc taaggtcacg 780
tgtgttgtgg tagacatcag caaggatgat cccgaggtcc agttcagctg gtttgtagat 840
gatgtggagg tgcacacagc tcagacgcaa ccccgggagg agcagttcaa cagcactttc 900
cgctcagtca gtgaacttcc catcatgcac caggactggc tcaatggcaa ggagttcaaa 960
tgcagggtca acagtgcagc tttccctgcc cccatcgaga aaaccatctc caaaaccaaa 1020
ggcagaccga aggctccaca ggtgtacacc attccacctc ccaaggagca gatggccaag 1080
gataaagtca gtctgacctg catgataaca gacttcttcc ctgaagacat tactgtggag 1140
tggcagtgga atgggcagcc agcggagaac tacaagaaca ctcagcccat catggacaca 1200
gatggctctt acttcatcta cagcaagctc aatgtgcaga agagcaactg ggaggcagga 1260
aatactttca cctgctctgt gttacatgag ggcctgcaca accaccatac tgagaagagc 1320
ctctcccact ctcctggtaa a 1341
<210> 163
<211> 466
<212> PRT
<213> 家鼷鼠
<400> 163
Met Gly Trp Ser Trp Thr Phe Leu Phe Leu Leu Ser Gly Thr Ala Gly
1 5 10 15
Val Leu Ser Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Met Lys
20 25 30
Pro Gly Ala Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe
35 40 45
Thr Asp Tyr Asn Met His Trp Met Lys Gln Asn Gln Gly Lys Ser Leu
50 55 60
Glu Trp Ile Gly Glu Ile Asn Pro Asn Ser Gly Gly Ala Gly Tyr Asn
65 70 75 80
Gln Gln Phe Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Arg
85 90 95
Thr Ala Tyr Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Leu Gly Tyr Val Gly Asn Tyr Glu Asp Trp Tyr
115 120 125
Phe Asp Val Trp Gly Ala Gly Thr Thr Val Thr Val Ser Ser Ala Lys
130 135 140
Thr Thr Pro Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln
145 150 155 160
Thr Asn Ser Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro
165 170 175
Glu Pro Val Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val
180 185 190
His Thr Phe Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser
195 200 205
Ser Val Thr Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val Thr Cys
210 215 220
Asn Val Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val
225 230 235 240
Pro Arg Asp Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val
245 250 255
Ser Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile
260 265 270
Thr Leu Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp
275 280 285
Asp Pro Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His
290 295 300
Thr Ala Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg
305 310 315 320
Ser Val Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys
325 330 335
Glu Phe Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu
340 345 350
Lys Thr Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr
355 360 365
Thr Ile Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu
370 375 380
Thr Cys Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp
385 390 395 400
Gln Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile
405 410 415
Met Asp Thr Asp Gly Ser Tyr Phe Ile Tyr Ser Lys Leu Asn Val Gln
420 425 430
Lys Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His
435 440 445
Glu Gly Leu His Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro
450 455 460
Gly Lys
465
<210> 164
<211> 1398
<212> DNA
<213> 家鼷鼠
<400> 164
atgggatgga gctggacctt tctcttcctc ctgtcaggaa ctgcaggtgt cctctctgag 60
gtccagctgc aacagtctgg acctgaacta atgaagcctg gggcttcagt gaagatgtcc 120
tgcaaggctt ctggatacac attcactgac tacaacatgc actggatgaa gcagaaccaa 180
ggaaagagcc tagaatggat aggagaaatt aatcctaaca gtggtggtgc tggctacaac 240
cagcagttca aaggcaaggc cacattgact gtagacaagt cctccaggac agcctacatg 300
gagctccgca gcctgacatc tgaggactct gcagtctatt actgtgcaag attgggctac 360
gttggtaatt acgaggactg gtacttcgat gtctggggcg cagggaccac ggtcaccgtc 420
tcctcagcca aaacgacacc cccatctgtc tatccactgg cccctggatc tgctgcccaa 480
actaactcca tggtgaccct gggatgcctg gtcaagggct atttccctga gccagtgaca 540
gtgacctgga actctggatc cctgtccagc ggtgtgcaca ccttcccagc tgtcctgcag 600
tctgacctct acactctgag cagctcagtg actgtcccct ccagcacctg gcccagcgag 660
accgtcacct gcaacgttgc ccacccggcc agcagcacca aggtggacaa gaaaattgtg 720
cccagggatt gtggttgtaa gccttgcata tgtacagtcc cagaagtatc atctgtcttc 780
atcttccccc caaagcccaa ggatgtgctc accattactc tgactcctaa ggtcacgtgt 840
gttgtggtag acatcagcaa ggatgatccc gaggtccagt tcagctggtt tgtagatgat 900
gtggaggtgc acacagctca gacgcaaccc cgggaggagc agttcaacag cactttccgc 960
tcagtcagtg aacttcccat catgcaccag gactggctca atggcaagga gttcaaatgc 1020
agggtcaaca gtgcagcttt ccctgccccc atcgagaaaa ccatctccaa aaccaaaggc 1080
agaccgaagg ctccacaggt gtacaccatt ccacctccca aggagcagat ggccaaggat 1140
aaagtcagtc tgacctgcat gataacagac ttcttccctg aagacattac tgtggagtgg 1200
cagtggaatg ggcagccagc ggagaactac aagaacactc agcccatcat ggacacagat 1260
ggctcttact tcatctacag caagctcaat gtgcagaaga gcaactggga ggcaggaaat 1320
actttcacct gctctgtgtt acatgagggc ctgcacaacc accatactga gaagagcctc 1380
tcccactctc ctggtaaa 1398
<210> 165
<211> 214
<212> PRT
<213> 家鼷鼠
<400> 165
Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser Ala Ser Leu Gly
1 5 10 15
Asp Arg Val Ser Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Asn Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Phe Lys Leu Leu Ile
35 40 45
Phe Tyr Thr Ser Arg Leu Leu Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Tyr Asn Leu Glu Gln
65 70 75 80
Glu Asp Phe Ala Thr Tyr Phe Cys Gln Gln Gly Asp Thr Leu Pro Tyr
85 90 95
Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Ala Asp Ala Ala
100 105 110
Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln Leu Thr Ser Gly
115 120 125
Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr Pro Lys Asp Ile
130 135 140
Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln Asn Gly Val Leu
145 150 155 160
Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr Tyr Ser Met Ser
165 170 175
Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg His Asn Ser Tyr
180 185 190
Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro Ile Val Lys Ser
195 200 205
Phe Asn Arg Asn Glu Cys
210
<210> 166
<211> 645
<212> DNA
<213> 家鼷鼠
<400> 166
gatatccaga tgacacagac tacatcctcc ctgtctgcct ctctgggaga cagggtctcc 60
atcagttgca gggcaagtca agacattagc aattatttaa actggtatca gcagaaacca 120
gatggaactt ttaaactcct tatcttctac acatcaagat tactctcagg agtcccatca 180
aggttcagtg gcagtgggtc tggaacagat tattctctca ccatttacaa cctggagcaa 240
gaagattttg ccacttactt ttgccaacag ggagatacgc ttccgtacac tttcggaggg 300
gggaccaaac tggaaataaa acgggctgat gctgcaccaa ctgtatccat cttcccacca 360
tccagtgagc agttaacatc tggaggtgcc tcagtcgtgt gcttcttgaa caacttctac 420
cccaaagaca tcaatgtcaa gtggaagatt gatggcagtg aacgacaaaa tggcgtcctg 480
aacagttgga ctgatcagga cagcaaagac agcacctaca gcatgagcag caccctcacg 540
ttgaccaagg acgagtatga acgacataac agctatacct gtgaggccac tcacaagaca 600
tcaacttcac ccattgtcaa gagcttcaac aggaatgagt gttag 645
<210> 167
<211> 234
<212> PRT
<213> 家鼷鼠
<400> 167
Met Met Ser Ser Ala Gln Phe Leu Gly Leu Leu Leu Leu Cys Phe Gln
1 5 10 15
Gly Thr Arg Cys Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser
20 25 30
Ala Ser Leu Gly Asp Arg Val Ser Ile Ser Cys Arg Ala Ser Gln Asp
35 40 45
Ile Ser Asn Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Phe
50 55 60
Lys Leu Leu Ile Phe Tyr Thr Ser Arg Leu Leu Ser Gly Val Pro Ser
65 70 75 80
Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Tyr
85 90 95
Asn Leu Glu Gln Glu Asp Phe Ala Thr Tyr Phe Cys Gln Gln Gly Asp
100 105 110
Thr Leu Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
Ala Asp Ala Ala Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln
130 135 140
Leu Thr Ser Gly Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr
145 150 155 160
Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln
165 170 175
Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr
180 185 190
Tyr Ser Met Ser Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg
195 200 205
His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro
210 215 220
Ile Val Lys Ser Phe Asn Arg Asn Glu Cys
225 230
<210> 168
<211> 705
<212> DNA
<213> 家鼷鼠
<400> 168
atgatgtcct ctgctcagtt ccttggtctc ctgttgctct gttttcaagg taccagatgt 60
gatatccaga tgacacagac tacatcctcc ctgtctgcct ctctgggaga cagggtctcc 120
atcagttgca gggcaagtca agacattagc aattatttaa actggtatca gcagaaacca 180
gatggaactt ttaaactcct tatcttctac acatcaagat tactctcagg agtcccatca 240
aggttcagtg gcagtgggtc tggaacagat tattctctca ccatttacaa cctggagcaa 300
gaagattttg ccacttactt ttgccaacag ggagatacgc ttccgtacac tttcggaggg 360
gggaccaaac tggaaataaa acgggctgat gctgcaccaa ctgtatccat cttcccacca 420
tccagtgagc agttaacatc tggaggtgcc tcagtcgtgt gcttcttgaa caacttctac 480
cccaaagaca tcaatgtcaa gtggaagatt gatggcagtg aacgacaaaa tggcgtcctg 540
aacagttgga ctgatcagga cagcaaagac agcacctaca gcatgagcag caccctcacg 600
ttgaccaagg acgagtatga acgacataac agctatacct gtgaggccac tcacaagaca 660
tcaacttcac ccattgtcaa gagcttcaac aggaatgagt gttag 705
<210> 169
<211> 447
<212> PRT
<213> 家鼷鼠
<400> 169
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Met Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Asn Met His Trp Val Lys Gln Asn Gln Gly Lys Thr Leu Asp Trp Ile
35 40 45
Gly Glu Ile Asn Pro Asn Ser Gly Gly Ala Gly Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Thr Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Leu Gly Tyr Asp Asp Ile Tyr Asp Asp Trp Tyr Phe Asp Val
100 105 110
Trp Gly Ala Gly Thr Thr Val Thr Val Ser Ser Ala Lys Thr Thr Pro
115 120 125
Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr Asn Ser
130 135 140
Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val
145 150 155 160
Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr Phe
165 170 175
Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr
180 185 190
Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val Thr Cys Asn Val Ala
195 200 205
His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val Pro Arg Asp
210 215 220
Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser Ser Val
225 230 235 240
Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr
245 250 255
Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu
260 265 270
Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln
275 280 285
Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser
290 295 300
Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys
305 310 315 320
Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile
325 330 335
Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro
340 345 350
Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met
355 360 365
Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn
370 375 380
Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr
385 390 395 400
Asp Gly Ser Tyr Phe Ile Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn
405 410 415
Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu
420 425 430
His Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys
435 440 445
<210> 170
<211> 1344
<212> DNA
<213> 家鼷鼠
<400> 170
gaggtccaac tgcaacagtc tggacctgaa ctaatgaagc ctggggcttc agtgaagatg 60
tcctgcaagg cttctggata tacattcact gactacaaca tgcactgggt gaagcagaac 120
caaggaaaga ccctagactg gataggagaa attaatccta acagtggtgg tgctggctac 180
aaccagaagt tcaagggcaa ggccacattg actgtagaca agtcctccac cacagcctac 240
atggagctcc gcagcctgac atctgaggac tctgcagtct attactgtgc aagattgggc 300
tacgatgata tctacgacga ctggtacttc gatgtctggg gcgcagggac cacggtcacc 360
gtctcctcag ccaaaacgac acccccatct gtctatccac tggcccctgg atctgctgcc 420
caaactaact ccatggtgac cctgggatgc ctggtcaagg gctatttccc tgagccagtg 480
acagtgacct ggaactctgg atccctgtcc agcggtgtgc acaccttccc agctgtcctg 540
cagtctgacc tctacactct gagcagctca gtgactgtcc cctccagcac ctggcccagc 600
gagaccgtca cctgcaacgt tgcccacccg gccagcagca ccaaggtgga caagaaaatt 660
gtgcccaggg attgtggttg taagccttgc atatgtacag tcccagaagt atcatctgtc 720
ttcatcttcc ccccaaagcc caaggatgtg ctcaccatta ctctgactcc taaggtcacg 780
tgtgttgtgg tagacatcag caaggatgat cccgaggtcc agttcagctg gtttgtagat 840
gatgtggagg tgcacacagc tcagacgcaa ccccgggagg agcagttcaa cagcactttc 900
cgctcagtca gtgaacttcc catcatgcac caggactggc tcaatggcaa ggagttcaaa 960
tgcagggtca acagtgcagc tttccctgcc cccatcgaga aaaccatctc caaaaccaaa 1020
ggcagaccga aggctccaca ggtgtacacc attccacctc ccaaggagca gatggccaag 1080
gataaagtca gtctgacctg catgataaca gacttcttcc ctgaagacat tactgtggag 1140
tggcagtgga atgggcagcc agcggagaac tacaagaaca ctcagcccat catggacaca 1200
gatggctctt acttcatcta cagcaagctc aatgtgcaga agagcaactg ggaggcagga 1260
aatactttca cctgctctgt gttacatgag ggcctgcaca accaccatac tgagaagagc 1320
ctctcccact ctcctggtaa atga 1344
<210> 171
<211> 466
<212> PRT
<213> 家鼷鼠
<400> 171
Met Gly Trp Ser Trp Thr Phe Leu Phe Leu Leu Ser Gly Thr Ala Gly
1 5 10 15
Val Leu Ser Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Met Lys
20 25 30
Pro Gly Ala Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe
35 40 45
Thr Asp Tyr Asn Met His Trp Val Lys Gln Asn Gln Gly Lys Thr Leu
50 55 60
Asp Trp Ile Gly Glu Ile Asn Pro Asn Ser Gly Gly Ala Gly Tyr Asn
65 70 75 80
Gln Lys Phe Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Thr
85 90 95
Thr Ala Tyr Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Leu Gly Tyr Asp Asp Ile Tyr Asp Asp Trp Tyr
115 120 125
Phe Asp Val Trp Gly Ala Gly Thr Thr Val Thr Val Ser Ser Ala Lys
130 135 140
Thr Thr Pro Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln
145 150 155 160
Thr Asn Ser Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro
165 170 175
Glu Pro Val Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val
180 185 190
His Thr Phe Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser
195 200 205
Ser Val Thr Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val Thr Cys
210 215 220
Asn Val Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val
225 230 235 240
Pro Arg Asp Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val
245 250 255
Ser Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile
260 265 270
Thr Leu Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp
275 280 285
Asp Pro Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His
290 295 300
Thr Ala Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg
305 310 315 320
Ser Val Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys
325 330 335
Glu Phe Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu
340 345 350
Lys Thr Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr
355 360 365
Thr Ile Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu
370 375 380
Thr Cys Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp
385 390 395 400
Gln Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile
405 410 415
Met Asp Thr Asp Gly Ser Tyr Phe Ile Tyr Ser Lys Leu Asn Val Gln
420 425 430
Lys Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His
435 440 445
Glu Gly Leu His Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro
450 455 460
Gly Lys
465
<210> 172
<211> 1401
<212> DNA
<213> 家鼷鼠
<400> 172
atgggatgga gctggacctt tctcttcctc ctgtcaggaa ctgcaggtgt cctctctgag 60
gtccaactgc aacagtctgg acctgaacta atgaagcctg gggcttcagt gaagatgtcc 120
tgcaaggctt ctggatatac attcactgac tacaacatgc actgggtgaa gcagaaccaa 180
ggaaagaccc tagactggat aggagaaatt aatcctaaca gtggtggtgc tggctacaac 240
cagaagttca agggcaaggc cacattgact gtagacaagt cctccaccac agcctacatg 300
gagctccgca gcctgacatc tgaggactct gcagtctatt actgtgcaag attgggctac 360
gatgatatct acgacgactg gtacttcgat gtctggggcg cagggaccac ggtcaccgtc 420
tcctcagcca aaacgacacc cccatctgtc tatccactgg cccctggatc tgctgcccaa 480
actaactcca tggtgaccct gggatgcctg gtcaagggct atttccctga gccagtgaca 540
gtgacctgga actctggatc cctgtccagc ggtgtgcaca ccttcccagc tgtcctgcag 600
tctgacctct acactctgag cagctcagtg actgtcccct ccagcacctg gcccagcgag 660
accgtcacct gcaacgttgc ccacccggcc agcagcacca aggtggacaa gaaaattgtg 720
cccagggatt gtggttgtaa gccttgcata tgtacagtcc cagaagtatc atctgtcttc 780
atcttccccc caaagcccaa ggatgtgctc accattactc tgactcctaa ggtcacgtgt 840
gttgtggtag acatcagcaa ggatgatccc gaggtccagt tcagctggtt tgtagatgat 900
gtggaggtgc acacagctca gacgcaaccc cgggaggagc agttcaacag cactttccgc 960
tcagtcagtg aacttcccat catgcaccag gactggctca atggcaagga gttcaaatgc 1020
agggtcaaca gtgcagcttt ccctgccccc atcgagaaaa ccatctccaa aaccaaaggc 1080
agaccgaagg ctccacaggt gtacaccatt ccacctccca aggagcagat ggccaaggat 1140
aaagtcagtc tgacctgcat gataacagac ttcttccctg aagacattac tgtggagtgg 1200
cagtggaatg ggcagccagc ggagaactac aagaacactc agcccatcat ggacacagat 1260
ggctcttact tcatctacag caagctcaat gtgcagaaga gcaactggga ggcaggaaat 1320
actttcacct gctctgtgtt acatgagggc ctgcacaacc accatactga gaagagcctc 1380
tcccactctc ctggtaaatg a 1401
<210> 173
<211> 214
<212> PRT
<213> 家鼷鼠
<400> 173
Asp Ile Gln Met Thr Gln Ile Thr Ser Ser Leu Ser Ala Ser Leu Gly
1 5 10 15
Asp Arg Val Ser Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Asn Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Phe Lys Leu Leu Ile
35 40 45
Phe Tyr Thr Ser Arg Leu Phe Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Tyr Asn Leu Glu Gln
65 70 75 80
Glu Asp Phe Ala Thr Tyr Phe Cys Gln Gln Gly Asp Thr Leu Pro Tyr
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Ala Asp Ala Ala
100 105 110
Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln Leu Thr Ser Gly
115 120 125
Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr Pro Lys Asp Ile
130 135 140
Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln Asn Gly Val Leu
145 150 155 160
Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr Tyr Ser Met Ser
165 170 175
Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg His Asn Ser Tyr
180 185 190
Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro Ile Val Lys Ser
195 200 205
Phe Asn Arg Asn Glu Cys
210
<210> 174
<211> 642
<212> DNA
<213> 家鼷鼠
<400> 174
gatatccaga tgacacagat tacatcctcc ctgtctgcct ctctgggaga cagggtctcc 60
atcagttgca gggcaagtca agacattagc aattatttaa attggtatca gcagaaacca 120
gatggaactt ttaaactcct tatcttctac acatcaagat tattttcagg agtcccatca 180
aggttcagtg gcagtgggtc tggaacagat tattctctca ccatttacaa cctggagcaa 240
gaagattttg ccacttactt ttgccaacag ggagatacgc ttccgtacac tttcggaggg 300
gggaccaagg tggaaataaa acgggctgat gctgcaccaa ctgtatccat cttcccacca 360
tccagtgagc agttaacatc tggaggtgcc tcagtcgtgt gcttcttgaa caacttctac 420
cccaaagaca tcaatgtcaa gtggaagatt gatggcagtg aacgacaaaa tggcgtcctg 480
aacagttgga ctgatcagga cagcaaagac agcacctaca gcatgagcag caccctcacg 540
ttgaccaagg acgagtatga acgacataac agctatacct gtgaggccac tcacaagaca 600
tcaacttcac ccattgtcaa gagcttcaac aggaatgagt gt 642
<210> 175
<211> 234
<212> PRT
<213> 家鼷鼠
<400> 175
Met Met Ser Ser Ala Gln Phe Leu Gly Leu Leu Leu Leu Cys Phe Gln
1 5 10 15
Gly Thr Arg Cys Asp Ile Gln Met Thr Gln Ile Thr Ser Ser Leu Ser
20 25 30
Ala Ser Leu Gly Asp Arg Val Ser Ile Ser Cys Arg Ala Ser Gln Asp
35 40 45
Ile Ser Asn Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Phe
50 55 60
Lys Leu Leu Ile Phe Tyr Thr Ser Arg Leu Phe Ser Gly Val Pro Ser
65 70 75 80
Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Tyr
85 90 95
Asn Leu Glu Gln Glu Asp Phe Ala Thr Tyr Phe Cys Gln Gln Gly Asp
100 105 110
Thr Leu Pro Tyr Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
115 120 125
Ala Asp Ala Ala Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln
130 135 140
Leu Thr Ser Gly Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr
145 150 155 160
Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln
165 170 175
Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr
180 185 190
Tyr Ser Met Ser Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg
195 200 205
His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro
210 215 220
Ile Val Lys Ser Phe Asn Arg Asn Glu Cys
225 230
<210> 176
<211> 702
<212> DNA
<213> 家鼷鼠
<400> 176
atgatgtcct ctgctcagtt ccttggtctc ctgttgctct gttttcaagg taccagatgt 60
gatatccaga tgacacagat tacatcctcc ctgtctgcct ctctgggaga cagggtctcc 120
atcagttgca gggcaagtca agacattagc aattatttaa attggtatca gcagaaacca 180
gatggaactt ttaaactcct tatcttctac acatcaagat tattttcagg agtcccatca 240
aggttcagtg gcagtgggtc tggaacagat tattctctca ccatttacaa cctggagcaa 300
gaagattttg ccacttactt ttgccaacag ggagatacgc ttccgtacac tttcggaggg 360
gggaccaagg tggaaataaa acgggctgat gctgcaccaa ctgtatccat cttcccacca 420
tccagtgagc agttaacatc tggaggtgcc tcagtcgtgt gcttcttgaa caacttctac 480
cccaaagaca tcaatgtcaa gtggaagatt gatggcagtg aacgacaaaa tggcgtcctg 540
aacagttgga ctgatcagga cagcaaagac agcacctaca gcatgagcag caccctcacg 600
ttgaccaagg acgagtatga acgacataac agctatacct gtgaggccac tcacaagaca 660
tcaacttcac ccattgtcaa gagcttcaac aggaatgagt gt 702
<210> 177
<211> 450
<212> PRT
<213> 家鼷鼠
<400> 177
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Met Lys Pro Gly Thr
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Asn Met His Trp Val Lys Gln Thr Gln Gly Lys Thr Leu Glu Trp Ile
35 40 45
Gly Glu Ile Asn Pro Asn Ser Gly Gly Ala Gly Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Thr Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Lys Leu Gly Tyr Asp Asp Ile Tyr Asp Asp Trp Tyr Phe Asp Val
100 105 110
Trp Gly Ala Gly Thr Thr Val Thr Val Ser Ser Ala Lys Thr Thr Ala
115 120 125
Pro Ser Val Tyr Pro Leu Ala Pro Val Cys Gly Asp Thr Thr Gly Ser
130 135 140
Ser Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val
145 150 155 160
Thr Leu Thr Trp Asn Ser Gly Ser Leu Ser Ser Asp Val His Thr Phe
165 170 175
Pro Ala Leu Leu Gln Ser Gly Leu Tyr Thr Leu Ser Ser Ser Val Thr
180 185 190
Val Thr Thr Trp Pro Ser Gln Thr Ile Thr Cys Asn Val Ala His Pro
195 200 205
Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Glu Pro Arg Gly Ser Pro
210 215 220
Thr His Lys Pro Cys Pro Pro Cys Pro Ala Pro Asn Leu Leu Gly Gly
225 230 235 240
Pro Ser Val Phe Ile Phe Pro Pro Lys Ile Lys Asp Val Leu Met Ile
245 250 255
Ser Leu Ser Pro Met Val Thr Cys Val Val Val Asp Val Ser Glu Asp
260 265 270
Asp Pro Asp Val His Val Ser Trp Phe Val Asn Asn Val Glu Val His
275 280 285
Thr Ala Gln Thr Gln Thr His Arg Glu Asp Tyr Asn Ser Thr Ile Arg
290 295 300
Val Val Ser Ala Leu Pro Ile Gln His Gln Asp Trp Met Ser Gly Lys
305 310 315 320
Glu Phe Lys Cys Lys Val Asn Asn Lys Ala Leu Pro Ala Pro Ile Glu
325 330 335
Arg Thr Ile Ser Lys Pro Lys Gly Pro Val Arg Ala Pro Gln Val Tyr
340 345 350
Val Leu Pro Pro Pro Glu Glu Glu Met Thr Lys Lys Gln Val Thr Leu
355 360 365
Thr Cys Met Ile Thr Asp Phe Met Pro Glu Asp Ile Tyr Val Glu Trp
370 375 380
Thr Asn Asn Gly Gln Thr Glu Leu Asn Tyr Lys Asn Thr Glu Pro Val
385 390 395 400
Leu Asp Ser Asp Gly Ser Tyr Phe Met Tyr Ser Lys Leu Arg Val Glu
405 410 415
Lys Lys Asn Trp Val Glu Arg Asn Ser Tyr Ser Cys Ser Val Val His
420 425 430
Glu Gly Leu His Asn His His Thr Thr Lys Ser Phe Ser Arg Thr Pro
435 440 445
Gly Lys
450
<210> 178
<211> 1350
<212> DNA
<213> 家鼷鼠
<400> 178
gaggtccaac tgcaacagtc tggacctgaa ctaatgaagc ctgggacttc agtgaagatg 60
tcctgcaagg cttctggata tacattcact gactacaaca tgcactgggt gaagcagacc 120
caaggaaaga ccctagagtg gataggagaa attaatccta acagtggtgg tgctggctac 180
aaccagaagt tcaagggcaa ggccacattg actgtagaca agtcctccac cacagcctac 240
atggagctcc gcagcctgac atctgaggac tctgcagtct attactgtgc aaaattgggc 300
tacgatgata tctacgacga ctggtatttc gatgtctggg gcgcagggac cacggtcacc 360
gtctcctcag ccaaaacaac agccccatcg gtctatccac tggcccctgt gtgtggagat 420
acaactggct cctcggtgac tctaggatgc ctggtcaagg gttatttccc tgagccagtg 480
accttgacct ggaactctgg atccctgtcc agtgatgtgc acaccttccc agctctcctg 540
cagtctggcc tctacaccct cagcagctca gtgactgtaa ccacctggcc cagccagacc 600
atcacctgca atgtggccca cccggcaagc agcaccaaag tggacaagaa aattgagccc 660
agagggtccc caacacataa accctgtcct ccatgcccag ctcctaacct cttgggtgga 720
ccatccgtct tcatcttccc tccaaagatc aaggatgtac tcatgatctc cctgagcccc 780
atggtcacgt gtgtggtggt ggatgtgagc gaggatgacc cagatgtcca tgtcagctgg 840
ttcgtgaaca acgtggaagt acacacagct cagacacaaa cccatagaga ggattacaac 900
agtactatcc gggtggtcag tgccctcccc atccagcacc aggactggat gagtggcaag 960
gagttcaaat gcaaggtcaa caacaaagcc ctcccagcgc ccatcgagag aaccatctca 1020
aaacccaaag ggccagtaag agctccacag gtatatgtct tgcctccacc agaagaagag 1080
atgactaaga aacaggtcac tctgacctgc atgatcacag acttcatgcc tgaagacatt 1140
tacgtggagt ggaccaacaa cgggcaaaca gagctaaact acaagaacac tgaaccagtc 1200
ctggactctg atggttctta cttcatgtac agcaagctga gagtggaaaa gaagaactgg 1260
gtggaaagaa atagctactc ctgttcagtg gtccacgagg gtctgcacaa tcaccacacg 1320
actaagagct tctcccggac tccgggtaaa 1350
<210> 179
<211> 469
<212> PRT
<213> 家鼷鼠
<400> 179
Met Gly Trp Ser Trp Thr Phe Leu Phe Leu Leu Ser Gly Thr Ala Gly
1 5 10 15
Val Leu Ser Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Met Lys
20 25 30
Pro Gly Thr Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe
35 40 45
Thr Asp Tyr Asn Met His Trp Val Lys Gln Thr Gln Gly Lys Thr Leu
50 55 60
Glu Trp Ile Gly Glu Ile Asn Pro Asn Ser Gly Gly Ala Gly Tyr Asn
65 70 75 80
Gln Lys Phe Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Thr
85 90 95
Thr Ala Tyr Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val
100 105 110
Tyr Tyr Cys Ala Lys Leu Gly Tyr Asp Asp Ile Tyr Asp Asp Trp Tyr
115 120 125
Phe Asp Val Trp Gly Ala Gly Thr Thr Val Thr Val Ser Ser Ala Lys
130 135 140
Thr Thr Ala Pro Ser Val Tyr Pro Leu Ala Pro Val Cys Gly Asp Thr
145 150 155 160
Thr Gly Ser Ser Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro
165 170 175
Glu Pro Val Thr Leu Thr Trp Asn Ser Gly Ser Leu Ser Ser Asp Val
180 185 190
His Thr Phe Pro Ala Leu Leu Gln Ser Gly Leu Tyr Thr Leu Ser Ser
195 200 205
Ser Val Thr Val Thr Thr Trp Pro Ser Gln Thr Ile Thr Cys Asn Val
210 215 220
Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Glu Pro Arg
225 230 235 240
Gly Ser Pro Thr His Lys Pro Cys Pro Pro Cys Pro Ala Pro Asn Leu
245 250 255
Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Ile Lys Asp Val
260 265 270
Leu Met Ile Ser Leu Ser Pro Met Val Thr Cys Val Val Val Asp Val
275 280 285
Ser Glu Asp Asp Pro Asp Val His Val Ser Trp Phe Val Asn Asn Val
290 295 300
Glu Val His Thr Ala Gln Thr Gln Thr His Arg Glu Asp Tyr Asn Ser
305 310 315 320
Thr Ile Arg Val Val Ser Ala Leu Pro Ile Gln His Gln Asp Trp Met
325 330 335
Ser Gly Lys Glu Phe Lys Cys Lys Val Asn Asn Lys Ala Leu Pro Ala
340 345 350
Pro Ile Glu Arg Thr Ile Ser Lys Pro Lys Gly Pro Val Arg Ala Pro
355 360 365
Gln Val Tyr Val Leu Pro Pro Pro Glu Glu Glu Met Thr Lys Lys Gln
370 375 380
Val Thr Leu Thr Cys Met Ile Thr Asp Phe Met Pro Glu Asp Ile Tyr
385 390 395 400
Val Glu Trp Thr Asn Asn Gly Gln Thr Glu Leu Asn Tyr Lys Asn Thr
405 410 415
Glu Pro Val Leu Asp Ser Asp Gly Ser Tyr Phe Met Tyr Ser Lys Leu
420 425 430
Arg Val Glu Lys Lys Asn Trp Val Glu Arg Asn Ser Tyr Ser Cys Ser
435 440 445
Val Val His Glu Gly Leu His Asn His His Thr Thr Lys Ser Phe Ser
450 455 460
Arg Thr Pro Gly Lys
465
<210> 180
<211> 1407
<212> DNA
<213> 家鼷鼠
<400> 180
atgggatgga gctggacctt tctcttcctc ctgtcaggaa ctgcaggtgt cctctctgag 60
gtccaactgc aacagtctgg acctgaacta atgaagcctg ggacttcagt gaagatgtcc 120
tgcaaggctt ctggatatac attcactgac tacaacatgc actgggtgaa gcagacccaa 180
ggaaagaccc tagagtggat aggagaaatt aatcctaaca gtggtggtgc tggctacaac 240
cagaagttca agggcaaggc cacattgact gtagacaagt cctccaccac agcctacatg 300
gagctccgca gcctgacatc tgaggactct gcagtctatt actgtgcaaa attgggctac 360
gatgatatct acgacgactg gtatttcgat gtctggggcg cagggaccac ggtcaccgtc 420
tcctcagcca aaacaacagc cccatcggtc tatccactgg cccctgtgtg tggagataca 480
actggctcct cggtgactct aggatgcctg gtcaagggtt atttccctga gccagtgacc 540
ttgacctgga actctggatc cctgtccagt gatgtgcaca ccttcccagc tctcctgcag 600
tctggcctct acaccctcag cagctcagtg actgtaacca cctggcccag ccagaccatc 660
acctgcaatg tggcccaccc ggcaagcagc accaaagtgg acaagaaaat tgagcccaga 720
gggtccccaa cacataaacc ctgtcctcca tgcccagctc ctaacctctt gggtggacca 780
tccgtcttca tcttccctcc aaagatcaag gatgtactca tgatctccct gagccccatg 840
gtcacgtgtg tggtggtgga tgtgagcgag gatgacccag atgtccatgt cagctggttc 900
gtgaacaacg tggaagtaca cacagctcag acacaaaccc atagagagga ttacaacagt 960
actatccggg tggtcagtgc cctccccatc cagcaccagg actggatgag tggcaaggag 1020
ttcaaatgca aggtcaacaa caaagccctc ccagcgccca tcgagagaac catctcaaaa 1080
cccaaagggc cagtaagagc tccacaggta tatgtcttgc ctccaccaga agaagagatg 1140
actaagaaac aggtcactct gacctgcatg atcacagact tcatgcctga agacatttac 1200
gtggagtgga ccaacaacgg gcaaacagag ctaaactaca agaacactga accagtcctg 1260
gactctgatg gttcttactt catgtacagc aagctgagag tggaaaagaa gaactgggtg 1320
gaaagaaata gctactcctg ttcagtggtc cacgagggtc tgcacaatca ccacacgact 1380
aagagcttct cccggactcc gggtaaa 1407
<210> 181
<211> 214
<212> PRT
<213> 家鼷鼠
<400> 181
Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser Ala Ser Leu Gly
1 5 10 15
Asp Arg Val Ser Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Asn Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Phe Lys Leu Leu Ile
35 40 45
Phe Tyr Thr Ser Arg Leu Leu Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Tyr Asn Leu Glu Gln
65 70 75 80
Glu Asp Phe Ala Thr Tyr Phe Cys Gln Gln Gly Asp Thr Leu Pro Tyr
85 90 95
Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Ala Asp Ala Ala
100 105 110
Pro Thr Val Ser Ile Phe Pro Leu Ser Ser Glu Gln Leu Thr Ser Gly
115 120 125
Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr Pro Lys Asp Ile
130 135 140
Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln Asn Gly Val Leu
145 150 155 160
Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr Tyr Ser Met Ser
165 170 175
Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg His Asn Ser Tyr
180 185 190
Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro Ile Val Lys Ser
195 200 205
Phe Asn Arg Asn Glu Cys
210
<210> 182
<211> 645
<212> DNA
<213> 家鼷鼠
<400> 182
gatatccaga tgacacagac tacatcctcc ctgtctgcct ctctgggaga cagggtctcc 60
atcagttgca gggcaagtca agacattagc aattatttaa actggtatca gcagaaacca 120
gatggaactt ttaaactcct tatcttctac acatcaagat tactctcagg agtcccatca 180
aggttcagtg gcagtgggtc tggaacagat tattctctca ccatttacaa cctggagcaa 240
gaagattttg ccacttactt ttgccaacag ggagatacgc ttccgtacac tttcggaggg 300
gggaccaaac tggaaataaa acgggctgat gctgcaccaa ctgtatccat cttcccacta 360
tccagtgagc agttaacatc tggaggtgcc tcagtcgtgt gcttcttgaa caacttctac 420
cccaaagaca tcaatgtcaa gtggaagatt gatggcagtg aacgacaaaa tggcgtcctg 480
aacagttgga ctgatcagga cagcaaagac agcacctaca gcatgagcag caccctcacg 540
ttgaccaagg acgagtatga acgacataac agctatacct gtgaggccac tcacaagaca 600
tcaacttcac ccattgtcaa gagcttcaac aggaatgagt gttag 645
<210> 183
<211> 234
<212> PRT
<213> 家鼷鼠
<400> 183
Met Met Ser Ser Ala Gln Phe Leu Gly Leu Leu Leu Leu Cys Phe Gln
1 5 10 15
Gly Thr Arg Cys Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser
20 25 30
Ala Ser Leu Gly Asp Arg Val Ser Ile Ser Cys Arg Ala Ser Gln Asp
35 40 45
Ile Ser Asn Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Phe
50 55 60
Lys Leu Leu Ile Phe Tyr Thr Ser Arg Leu Leu Ser Gly Val Pro Ser
65 70 75 80
Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Tyr
85 90 95
Asn Leu Glu Gln Glu Asp Phe Ala Thr Tyr Phe Cys Gln Gln Gly Asp
100 105 110
Thr Leu Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
Ala Asp Ala Ala Pro Thr Val Ser Ile Phe Pro Leu Ser Ser Glu Gln
130 135 140
Leu Thr Ser Gly Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr
145 150 155 160
Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln
165 170 175
Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr
180 185 190
Tyr Ser Met Ser Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg
195 200 205
His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro
210 215 220
Ile Val Lys Ser Phe Asn Arg Asn Glu Cys
225 230
<210> 184
<211> 705
<212> DNA
<213> 家鼷鼠
<400> 184
atgatgtcct ctgctcagtt ccttggtctc ctgttgctct gttttcaagg taccagatgt 60
gatatccaga tgacacagac tacatcctcc ctgtctgcct ctctgggaga cagggtctcc 120
atcagttgca gggcaagtca agacattagc aattatttaa actggtatca gcagaaacca 180
gatggaactt ttaaactcct tatcttctac acatcaagat tactctcagg agtcccatca 240
aggttcagtg gcagtgggtc tggaacagat tattctctca ccatttacaa cctggagcaa 300
gaagattttg ccacttactt ttgccaacag ggagatacgc ttccgtacac tttcggaggg 360
gggaccaaac tggaaataaa acgggctgat gctgcaccaa ctgtatccat cttcccacta 420
tccagtgagc agttaacatc tggaggtgcc tcagtcgtgt gcttcttgaa caacttctac 480
cccaaagaca tcaatgtcaa gtggaagatt gatggcagtg aacgacaaaa tggcgtcctg 540
aacagttgga ctgatcagga cagcaaagac agcacctaca gcatgagcag caccctcacg 600
ttgaccaagg acgagtatga acgacataac agctatacct gtgaggccac tcacaagaca 660
tcaacttcac ccattgtcaa gagcttcaac aggaatgagt gttag 705
<210> 185
<211> 447
<212> PRT
<213> 家鼷鼠
<400> 185
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Met Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Asn Met His Trp Val Lys Gln Asn Gln Gly Lys Thr Leu Glu Trp Ile
35 40 45
Gly Glu Ile Asn Pro Asn Ser Gly Gly Ala Gly Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Thr Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Leu Gly Tyr Asp Asp Ile Tyr Asp Asp Trp Tyr Phe Asp Val
100 105 110
Trp Gly Ala Gly Thr Thr Val Thr Val Ser Ser Ala Lys Thr Thr Pro
115 120 125
Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr Asn Ser
130 135 140
Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val
145 150 155 160
Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr Phe
165 170 175
Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr
180 185 190
Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val Thr Cys Asn Val Ala
195 200 205
His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val Pro Arg Asp
210 215 220
Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser Ser Val
225 230 235 240
Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr
245 250 255
Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu
260 265 270
Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln
275 280 285
Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser
290 295 300
Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys
305 310 315 320
Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile
325 330 335
Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro
340 345 350
Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met
355 360 365
Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn
370 375 380
Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr
385 390 395 400
Asp Gly Ser Tyr Phe Ile Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn
405 410 415
Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu
420 425 430
His Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys
435 440 445
<210> 186
<211> 1344
<212> DNA
<213> 家鼷鼠
<400> 186
gaggtccaac tgcaacagtc tggacctgaa ctaatgaagc ctggggcttc agtgaagatg 60
tcctgcaagg cttctggata tacattcact gactacaaca tgcactgggt gaagcagaac 120
caaggaaaga ccctagaatg gataggagaa attaatccta acagtggtgg tgctggctac 180
aaccagaagt tcaagggcaa ggccacattg actgtagaca agtcctccac cacagcctac 240
atggagctcc gcagcctgac atctgaggac tctgcagtct attactgtgc aagattgggc 300
tacgatgata tctacgacga ctggtacttc gatgtctggg gcgcagggac cacggtcacc 360
gtctcctcag ccaaaacgac acccccatct gtctatccac tggcccctgg atctgctgcc 420
caaactaact ccatggtgac cctgggatgc ctggtcaagg gctatttccc tgagccagtg 480
acagtgacct ggaactctgg atccctgtcc agcggtgtgc acaccttccc agctgtcctg 540
cagtctgacc tctacactct gagcagctca gtgactgtcc cctccagcac ctggcccagc 600
gagaccgtca cctgcaacgt tgcccacccg gccagcagca ccaaggtgga caagaaaatt 660
gtgcccaggg attgtggttg taagccttgc atatgtacag tcccagaagt atcatctgtc 720
ttcatcttcc ccccaaagcc caaggatgtg ctcaccatta ctctgactcc taaggtcacg 780
tgtgttgtgg tagacatcag caaggatgat cccgaggtcc agttcagctg gtttgtagat 840
gatgtggagg tgcacacagc tcagacgcaa ccccgggagg agcagttcaa cagcactttc 900
cgctcagtca gtgaacttcc catcatgcac caggactggc tcaatggcaa ggagttcaaa 960
tgcagggtca acagtgcagc tttccctgcc cccatcgaga aaaccatctc caaaaccaaa 1020
ggcagaccga aggctccaca ggtgtacacc attccacctc ccaaggagca gatggccaag 1080
gataaagtca gtctgacctg catgataaca gacttcttcc ctgaagacat tactgtggag 1140
tggcagtgga atgggcagcc agcggagaac tacaagaaca ctcagcccat catggacaca 1200
gatggctctt acttcatcta cagcaagctc aatgtgcaga agagcaactg ggaggcagga 1260
aatactttca cctgctctgt gttacatgag ggcctgcaca accaccatac tgagaagagc 1320
ctctcccact ctcctggtaa atga 1344
<210> 187
<211> 466
<212> PRT
<213> 家鼷鼠
<400> 187
Met Gly Trp Ser Trp Thr Phe Leu Phe Leu Leu Ser Gly Thr Ala Gly
1 5 10 15
Val Leu Ser Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Met Lys
20 25 30
Pro Gly Ala Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe
35 40 45
Thr Asp Tyr Asn Met His Trp Val Lys Gln Asn Gln Gly Lys Thr Leu
50 55 60
Glu Trp Ile Gly Glu Ile Asn Pro Asn Ser Gly Gly Ala Gly Tyr Asn
65 70 75 80
Gln Lys Phe Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Thr
85 90 95
Thr Ala Tyr Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Leu Gly Tyr Asp Asp Ile Tyr Asp Asp Trp Tyr
115 120 125
Phe Asp Val Trp Gly Ala Gly Thr Thr Val Thr Val Ser Ser Ala Lys
130 135 140
Thr Thr Pro Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln
145 150 155 160
Thr Asn Ser Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro
165 170 175
Glu Pro Val Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val
180 185 190
His Thr Phe Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser
195 200 205
Ser Val Thr Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val Thr Cys
210 215 220
Asn Val Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val
225 230 235 240
Pro Arg Asp Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val
245 250 255
Ser Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile
260 265 270
Thr Leu Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp
275 280 285
Asp Pro Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His
290 295 300
Thr Ala Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg
305 310 315 320
Ser Val Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys
325 330 335
Glu Phe Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu
340 345 350
Lys Thr Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr
355 360 365
Thr Ile Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu
370 375 380
Thr Cys Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp
385 390 395 400
Gln Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile
405 410 415
Met Asp Thr Asp Gly Ser Tyr Phe Ile Tyr Ser Lys Leu Asn Val Gln
420 425 430
Lys Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His
435 440 445
Glu Gly Leu His Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro
450 455 460
Gly Lys
465
<210> 188
<211> 1401
<212> DNA
<213> 家鼷鼠
<400> 188
atgggatgga gctggacctt tctcttcctc ctgtcaggaa ctgcaggtgt cctctctgag 60
gtccaactgc aacagtctgg acctgaacta atgaagcctg gggcttcagt gaagatgtcc 120
tgcaaggctt ctggatatac attcactgac tacaacatgc actgggtgaa gcagaaccaa 180
ggaaagaccc tagaatggat aggagaaatt aatcctaaca gtggtggtgc tggctacaac 240
cagaagttca agggcaaggc cacattgact gtagacaagt cctccaccac agcctacatg 300
gagctccgca gcctgacatc tgaggactct gcagtctatt actgtgcaag attgggctac 360
gatgatatct acgacgactg gtacttcgat gtctggggcg cagggaccac ggtcaccgtc 420
tcctcagcca aaacgacacc cccatctgtc tatccactgg cccctggatc tgctgcccaa 480
actaactcca tggtgaccct gggatgcctg gtcaagggct atttccctga gccagtgaca 540
gtgacctgga actctggatc cctgtccagc ggtgtgcaca ccttcccagc tgtcctgcag 600
tctgacctct acactctgag cagctcagtg actgtcccct ccagcacctg gcccagcgag 660
accgtcacct gcaacgttgc ccacccggcc agcagcacca aggtggacaa gaaaattgtg 720
cccagggatt gtggttgtaa gccttgcata tgtacagtcc cagaagtatc atctgtcttc 780
atcttccccc caaagcccaa ggatgtgctc accattactc tgactcctaa ggtcacgtgt 840
gttgtggtag acatcagcaa ggatgatccc gaggtccagt tcagctggtt tgtagatgat 900
gtggaggtgc acacagctca gacgcaaccc cgggaggagc agttcaacag cactttccgc 960
tcagtcagtg aacttcccat catgcaccag gactggctca atggcaagga gttcaaatgc 1020
agggtcaaca gtgcagcttt ccctgccccc atcgagaaaa ccatctccaa aaccaaaggc 1080
agaccgaagg ctccacaggt gtacaccatt ccacctccca aggagcagat ggccaaggat 1140
aaagtcagtc tgacctgcat gataacagac ttcttccctg aagacattac tgtggagtgg 1200
cagtggaatg ggcagccagc ggagaactac aagaacactc agcccatcat ggacacagat 1260
ggctcttact tcatctacag caagctcaat gtgcagaaga gcaactggga ggcaggaaat 1320
actttcacct gctctgtgtt acatgagggc ctgcacaacc accatactga gaagagcctc 1380
tcccactctc ctggtaaatg a 1401
<210> 189
<211> 213
<212> PRT
<213> 家鼷鼠
<400> 189
Gln Ile Val Leu Ser Gln Ser Pro Ala Phe Leu Ser Val Ser Pro Gly
1 5 10 15
Asp Lys Val Thr Met Thr Cys Arg Ala Ser Ser Ser Ile Ser Tyr Ile
20 25 30
His Trp Phe Gln Gln Lys Pro Gly Ser Ser Pro Arg Ser Trp Ile Tyr
35 40 45
Ala Thr Ser Asn Leu Ala Ser Gly Val Pro Gly Arg Phe Ser Gly Ser
50 55 60
Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile Ser Arg Val Glu Ala Glu
65 70 75 80
Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Trp Ser Ser Asp Pro Leu Thr
85 90 95
Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys Arg Ala Asp Ala Ala Pro
100 105 110
Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln Leu Thr Ser Gly Gly
115 120 125
Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr Pro Lys Asp Ile Asn
130 135 140
Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln Asn Gly Val Leu Asn
145 150 155 160
Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr Tyr Ser Met Ser Ser
165 170 175
Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg His Asn Ser Tyr Thr
180 185 190
Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro Ile Val Lys Ser Phe
195 200 205
Asn Arg Asn Glu Cys
210
<210> 190
<211> 642
<212> DNA
<213> 家鼷鼠
<400> 190
caaattgttc tctcccagtc tccagcattc ctgtctgtat ctccagggga taaggtcaca 60
atgacttgca gggccagctc aagtataagt tacatacact ggtttcagca gaagccagga 120
tcctccccca gatcctggat ttatgccaca tccaacctgg cttctggagt ccctggtcgc 180
ttcagtggca gtgggtctgg gacctcttac tctctcacaa tcagcagagt ggaggctgag 240
gatgctgcca cttattactg ccagcagtgg agtagtgacc cactcacgtt cggtgctggg 300
accaagctgg agctgaaacg ggctgatgct gcaccaactg tatccatctt cccaccatcc 360
agtgagcagt taacatctgg aggtgcctca gtcgtgtgct tcttgaacaa cttctacccc 420
aaagacatca atgtcaagtg gaagattgat ggcagtgaac gacaaaatgg cgtcctgaac 480
agttggactg atcaggacag caaagacagc acctacagca tgagcagcac cctcacgttg 540
accaaggacg agtatgaacg acataacagc tatacctgtg aggccactca caagacatca 600
acttcaccca ttgtcaagag cttcaacagg aatgagtgtt ag 642
<210> 191
<211> 235
<212> PRT
<213> 家鼷鼠
<400> 191
Met Asp Phe Gln Val Gln Ile Phe Ser Phe Leu Leu Ile Ser Ala Ser
1 5 10 15
Val Ile Met Ser Arg Gly Gln Ile Val Leu Ser Gln Ser Pro Ala Phe
20 25 30
Leu Ser Val Ser Pro Gly Asp Lys Val Thr Met Thr Cys Arg Ala Ser
35 40 45
Ser Ser Ile Ser Tyr Ile His Trp Phe Gln Gln Lys Pro Gly Ser Ser
50 55 60
Pro Arg Ser Trp Ile Tyr Ala Thr Ser Asn Leu Ala Ser Gly Val Pro
65 70 75 80
Gly Arg Phe Ser Gly Ser Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile
85 90 95
Ser Arg Val Glu Ala Glu Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Trp
100 105 110
Ser Ser Asp Pro Leu Thr Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys
115 120 125
Arg Ala Asp Ala Ala Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu
130 135 140
Gln Leu Thr Ser Gly Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe
145 150 155 160
Tyr Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg
165 170 175
Gln Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser
180 185 190
Thr Tyr Ser Met Ser Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu
195 200 205
Arg His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser
210 215 220
Pro Ile Val Lys Ser Phe Asn Arg Asn Glu Cys
225 230 235
<210> 192
<211> 708
<212> DNA
<213> 家鼷鼠
<400> 192
atggattttc aagtgcagat tttcagcttc ctgctaatca gtgcttcagt cataatgtcc 60
agaggacaaa ttgttctctc ccagtctcca gcattcctgt ctgtatctcc aggggataag 120
gtcacaatga cttgcagggc cagctcaagt ataagttaca tacactggtt tcagcagaag 180
ccaggatcct cccccagatc ctggatttat gccacatcca acctggcttc tggagtccct 240
ggtcgcttca gtggcagtgg gtctgggacc tcttactctc tcacaatcag cagagtggag 300
gctgaggatg ctgccactta ttactgccag cagtggagta gtgacccact cacgttcggt 360
gctgggacca agctggagct gaaacgggct gatgctgcac caactgtatc catcttccca 420
ccatccagtg agcagttaac atctggaggt gcctcagtcg tgtgcttctt gaacaacttc 480
taccccaaag acatcaatgt caagtggaag attgatggca gtgaacgaca aaatggcgtc 540
ctgaacagtt ggactgatca ggacagcaaa gacagcacct acagcatgag cagcaccctc 600
acgttgacca aggacgagta tgaacgacat aacagctata cctgtgaggc cactcacaag 660
acatcaactt cacccattgt caagagcttc aacaggaatg agtgttag 708
<210> 193
<211> 445
<212> PRT
<213> 家鼷鼠
<400> 193
Glu Val Gln Leu Gln Gln Ser Gly Ala Asp Leu Val Gln Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Thr Ala Ser Gly Phe Asp Ile Lys Asp Tyr
20 25 30
Tyr Ile His Trp Met Lys Gln Arg Pro Asp Gln Gly Leu Glu Trp Ile
35 40 45
Gly Arg Val Asp Pro Asp Asn Gly Glu Thr Glu Phe Ala Pro Lys Phe
50 55 60
Pro Gly Lys Ala Thr Phe Thr Thr Asp Thr Ser Ser Asn Thr Ala Tyr
65 70 75 80
Leu Gln Leu Arg Gly Leu Thr Ser Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Gly Arg Glu Asp Tyr Asp Gly Thr Tyr Thr Trp Phe Pro Tyr Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ala Ala Lys Thr Thr Pro Pro Ser
115 120 125
Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr Asn Ser Met Val
130 135 140
Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val Thr Val
145 150 155 160
Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr Phe Pro Ala
165 170 175
Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr Val Pro
180 185 190
Ser Ser Thr Trp Pro Ser Glu Thr Val Thr Cys Asn Val Ala His Pro
195 200 205
Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val Pro Arg Asp Cys Gly
210 215 220
Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser Ser Val Phe Ile
225 230 235 240
Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro Lys
245 250 255
Val Thr Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu Val Gln
260 265 270
Phe Ser Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr Gln
275 280 285
Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser Glu Leu
290 295 300
Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg
305 310 315 320
Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys
325 330 335
Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro
340 345 350
Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile Thr
355 360 365
Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly Gln
370 375 380
Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr Asp Gly
385 390 395 400
Ser Tyr Phe Ile Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn Trp Glu
405 410 415
Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His Asn
420 425 430
His His Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys
435 440 445
<210> 194
<211> 1338
<212> DNA
<213> 家鼷鼠
<400> 194
gaagttcagc tgcaacagtc tggggcagac cttgtgcagc caggggcctc agtcaaggtg 60
tcctgcacag cttctggctt cgacattaag gactactata tacactggat gaaacagagg 120
cctgaccagg gcctggagtg gattggaagg gttgatcctg acaatggtga gactgaattt 180
gccccgaagt tcccgggcaa ggccactttt acaacagaca catcctccaa cacagcctac 240
ctacaactca gaggcctgac atctgaggac actgccatct attactgtgg gagagaagac 300
tacgatggta cctacacctg gtttccttat tggggccaag ggactctggt cactgtctct 360
gcagccaaaa cgacaccccc atctgtctat ccactggccc ctggatctgc tgcccaaact 420
aactccatgg tgaccctggg atgcctggtc aagggctatt tccctgagcc agtgacagtg 480
acctggaact ctggatccct gtccagcggt gtgcacacct tcccagctgt cctgcagtct 540
gacctctaca ctctgagcag ctcagtgact gtcccctcca gcacctggcc cagcgagacc 600
gtcacctgca acgttgccca cccggccagc agcaccaagg tggacaagaa aattgtgccc 660
agggattgtg gttgtaagcc ttgcatatgt acagtcccag aagtatcatc tgtcttcatc 720
ttccccccaa agcccaagga tgtgctcacc attactctga ctcctaaggt cacgtgtgtt 780
gtggtagaca tcagcaagga tgatcccgag gtccagttca gctggtttgt agatgatgtg 840
gaggtgcaca cagctcagac gcaaccccgg gaggagcagt tcaacagcac tttccgctca 900
gtcagtgaac ttcccatcat gcaccaggac tggctcaatg gcaaggagtt caaatgcagg 960
gtcaacagtg cagctttccc tgcccccatc gagaaaacca tctccaaaac caaaggcaga 1020
ccgaaggctc cacaggtgta caccattcca cctcccaagg agcagatggc caaggataaa 1080
gtcagtctga cctgcatgat aacagacttc ttccctgaag acattactgt ggagtggcag 1140
tggaatgggc agccagcgga gaactacaag aacactcagc ccatcatgga cacagatggc 1200
tcttacttca tctacagcaa gctcaatgtg cagaagagca actgggaggc aggaaatact 1260
ttcacctgct ctgtgttaca tgagggcctg cacaaccacc atactgagaa gagcctctcc 1320
cactctcctg gtaaatga 1338
<210> 195
<211> 464
<212> PRT
<213> 家鼷鼠
<400> 195
Met Lys Cys Ser Trp Val Ile Phe Phe Leu Met Ala Val Val Thr Gly
1 5 10 15
Val Asn Ser Glu Val Gln Leu Gln Gln Ser Gly Ala Asp Leu Val Gln
20 25 30
Pro Gly Ala Ser Val Lys Val Ser Cys Thr Ala Ser Gly Phe Asp Ile
35 40 45
Lys Asp Tyr Tyr Ile His Trp Met Lys Gln Arg Pro Asp Gln Gly Leu
50 55 60
Glu Trp Ile Gly Arg Val Asp Pro Asp Asn Gly Glu Thr Glu Phe Ala
65 70 75 80
Pro Lys Phe Pro Gly Lys Ala Thr Phe Thr Thr Asp Thr Ser Ser Asn
85 90 95
Thr Ala Tyr Leu Gln Leu Arg Gly Leu Thr Ser Glu Asp Thr Ala Ile
100 105 110
Tyr Tyr Cys Gly Arg Glu Asp Tyr Asp Gly Thr Tyr Thr Trp Phe Pro
115 120 125
Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala Ala Lys Thr Thr
130 135 140
Pro Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr Asn
145 150 155 160
Ser Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro
165 170 175
Val Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr
180 185 190
Phe Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val
195 200 205
Thr Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val Thr Cys Asn Val
210 215 220
Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val Pro Arg
225 230 235 240
Asp Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser Ser
245 250 255
Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu
260 265 270
Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro
275 280 285
Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His Thr Ala
290 295 300
Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val
305 310 315 320
Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe
325 330 335
Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr
340 345 350
Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile
355 360 365
Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys
370 375 380
Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp
385 390 395 400
Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp
405 410 415
Thr Asp Gly Ser Tyr Phe Ile Tyr Ser Lys Leu Asn Val Gln Lys Ser
420 425 430
Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly
435 440 445
Leu His Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys
450 455 460
<210> 196
<211> 1395
<212> DNA
<213> 家鼷鼠
<400> 196
atgaaatgca gctgggtcat cttcttcctg atggcagtgg ttacaggggt caattcagaa 60
gttcagctgc aacagtctgg ggcagacctt gtgcagccag gggcctcagt caaggtgtcc 120
tgcacagctt ctggcttcga cattaaggac tactatatac actggatgaa acagaggcct 180
gaccagggcc tggagtggat tggaagggtt gatcctgaca atggtgagac tgaatttgcc 240
ccgaagttcc cgggcaaggc cacttttaca acagacacat cctccaacac agcctaccta 300
caactcagag gcctgacatc tgaggacact gccatctatt actgtgggag agaagactac 360
gatggtacct acacctggtt tccttattgg ggccaaggga ctctggtcac tgtctctgca 420
gccaaaacga cacccccatc tgtctatcca ctggcccctg gatctgctgc ccaaactaac 480
tccatggtga ccctgggatg cctggtcaag ggctatttcc ctgagccagt gacagtgacc 540
tggaactctg gatccctgtc cagcggtgtg cacaccttcc cagctgtcct gcagtctgac 600
ctctacactc tgagcagctc agtgactgtc ccctccagca cctggcccag cgagaccgtc 660
acctgcaacg ttgcccaccc ggccagcagc accaaggtgg acaagaaaat tgtgcccagg 720
gattgtggtt gtaagccttg catatgtaca gtcccagaag tatcatctgt cttcatcttc 780
cccccaaagc ccaaggatgt gctcaccatt actctgactc ctaaggtcac gtgtgttgtg 840
gtagacatca gcaaggatga tcccgaggtc cagttcagct ggtttgtaga tgatgtggag 900
gtgcacacag ctcagacgca accccgggag gagcagttca acagcacttt ccgctcagtc 960
agtgaacttc ccatcatgca ccaggactgg ctcaatggca aggagttcaa atgcagggtc 1020
aacagtgcag ctttccctgc ccccatcgag aaaaccatct ccaaaaccaa aggcagaccg 1080
aaggctccac aggtgtacac cattccacct cccaaggagc agatggccaa ggataaagtc 1140
agtctgacct gcatgataac agacttcttc cctgaagaca ttactgtgga gtggcagtgg 1200
aatgggcagc cagcggagaa ctacaagaac actcagccca tcatggacac agatggctct 1260
tacttcatct acagcaagct caatgtgcag aagagcaact gggaggcagg aaatactttc 1320
acctgctctg tgttacatga gggcctgcac aaccaccata ctgagaagag cctctcccac 1380
tctcctggta aatga 1395
<210> 197
<211> 214
<212> PRT
<213> 家鼷鼠
<400> 197
Asp Leu Gln Met Thr Gln Thr Thr Ser Ser Leu Ser Ala Ser Leu Gly
1 5 10 15
Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Asn Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Val Lys Leu Leu Ile
35 40 45
Phe Tyr Thr Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asn Tyr Ser Leu Thr Ile Thr Asn Leu Glu Gln
65 70 75 80
Asp Asp Ala Ala Thr Tyr Phe Cys Gln Gln Gly Asp Thr Leu Pro Tyr
85 90 95
Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Ala Asp Ala Ala
100 105 110
Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln Leu Thr Ser Gly
115 120 125
Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr Pro Lys Asp Ile
130 135 140
Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln Asn Gly Val Leu
145 150 155 160
Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr Tyr Ser Met Ser
165 170 175
Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg His Asn Ser Tyr
180 185 190
Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro Ile Val Lys Ser
195 200 205
Phe Asn Arg Asn Glu Cys
210
<210> 198
<211> 645
<212> DNA
<213> 家鼷鼠
<400> 198
gatctccaga tgacacagac tacttcctcc ctgtctgcct ctctgggaga cagagtcacc 60
atcagttgca gggcaagtca ggacattagc aattatttaa actggtatca gcagaaacca 120
gatggaactg ttaagctcct gatcttctac acatcaacat tacagtcagg agtcccatcg 180
aggttcagtg gcagtgggtc tggaacaaat tattctctca ccattaccaa cctggagcaa 240
gatgatgctg ccacttactt ttgccaacag ggtgatacgc ttccgtacac gttcggaggg 300
gggaccaagc tggaaataaa acgggctgat gctgcaccaa ctgtatccat cttcccacca 360
tccagtgagc agttaacatc tggaggtgcc tcagtcgtgt gcttcttgaa caacttctac 420
cccaaagaca tcaatgtcaa gtggaagatt gatggcagtg aacgacaaaa tggcgtcctg 480
aacagttgga ctgatcagga cagcaaagac agcacctaca gcatgagcag caccctcacg 540
ttgaccaagg acgagtatga acgacataac agctatacct gtgaggccac tcacaagaca 600
tcaacttcac ccattgtcaa gagcttcaac aggaatgagt gttag 645
<210> 199
<211> 234
<212> PRT
<213> 家鼷鼠
<400> 199
Met Met Ser Ser Ala Gln Phe Leu Gly Leu Leu Leu Leu Cys Phe Gln
1 5 10 15
Gly Ser Arg Cys Asp Leu Gln Met Thr Gln Thr Thr Ser Ser Leu Ser
20 25 30
Ala Ser Leu Gly Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln Asp
35 40 45
Ile Ser Asn Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Val
50 55 60
Lys Leu Leu Ile Phe Tyr Thr Ser Thr Leu Gln Ser Gly Val Pro Ser
65 70 75 80
Arg Phe Ser Gly Ser Gly Ser Gly Thr Asn Tyr Ser Leu Thr Ile Thr
85 90 95
Asn Leu Glu Gln Asp Asp Ala Ala Thr Tyr Phe Cys Gln Gln Gly Asp
100 105 110
Thr Leu Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
Ala Asp Ala Ala Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln
130 135 140
Leu Thr Ser Gly Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr
145 150 155 160
Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln
165 170 175
Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr
180 185 190
Tyr Ser Met Ser Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg
195 200 205
His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro
210 215 220
Ile Val Lys Ser Phe Asn Arg Asn Glu Cys
225 230
<210> 200
<211> 705
<212> DNA
<213> 家鼷鼠
<400> 200
atgatgtcct ctgctcagtt ccttggtctc ctgttgctct gttttcaagg ttccagatgt 60
gatctccaga tgacacagac tacttcctcc ctgtctgcct ctctgggaga cagagtcacc 120
atcagttgca gggcaagtca ggacattagc aattatttaa actggtatca gcagaaacca 180
gatggaactg ttaagctcct gatcttctac acatcaacat tacagtcagg agtcccatcg 240
aggttcagtg gcagtgggtc tggaacaaat tattctctca ccattaccaa cctggagcaa 300
gatgatgctg ccacttactt ttgccaacag ggtgatacgc ttccgtacac gttcggaggg 360
gggaccaagc tggaaataaa acgggctgat gctgcaccaa ctgtatccat cttcccacca 420
tccagtgagc agttaacatc tggaggtgcc tcagtcgtgt gcttcttgaa caacttctac 480
cccaaagaca tcaatgtcaa gtggaagatt gatggcagtg aacgacaaaa tggcgtcctg 540
aacagttgga ctgatcagga cagcaaagac agcacctaca gcatgagcag caccctcacg 600
ttgaccaagg acgagtatga acgacataac agctatacct gtgaggccac tcacaagaca 660
tcaacttcac ccattgtcaa gagcttcaac aggaatgagt gttag 705
<210> 201
<211> 447
<212> PRT
<213> 家鼷鼠
<400> 201
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Met Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Asn Met His Trp Met Lys Gln Asn Gln Gly Lys Ser Leu Glu Trp Ile
35 40 45
Gly Glu Ile Asn Pro Asn Ser Gly Gly Ser Gly Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Leu Gly Tyr Tyr Gly Asn Tyr Glu Asp Trp Tyr Phe Asp Val
100 105 110
Trp Gly Ala Gly Thr Thr Val Thr Val Ser Ser Ala Lys Thr Thr Pro
115 120 125
Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr Asn Ser
130 135 140
Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val
145 150 155 160
Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr Phe
165 170 175
Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr
180 185 190
Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val Thr Cys Asn Val Ala
195 200 205
His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val Pro Arg Asp
210 215 220
Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser Ser Val
225 230 235 240
Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr
245 250 255
Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu
260 265 270
Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln
275 280 285
Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser
290 295 300
Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys
305 310 315 320
Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile
325 330 335
Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro
340 345 350
Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met
355 360 365
Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn
370 375 380
Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr
385 390 395 400
Asp Gly Ser Tyr Phe Ile Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn
405 410 415
Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu
420 425 430
His Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys
435 440 445
<210> 202
<211> 1344
<212> DNA
<213> 家鼷鼠
<400> 202
gaggtccagt tgcaacagtc tggacctgaa ctaatgaagc ctggggcttc agtgaagatg 60
tcctgcaagg cttctggata cacattcact gactacaaca tgcactggat gaagcagaac 120
caaggaaaga gcctagagtg gataggagag attaatccta acagtggtgg ttctggttac 180
aaccagaagt tcaaaggcaa ggccacattg actgtagaca agtcctccag cacagcctac 240
atggagctcc gcagcctgac atctgaggac tctgcagtct attactgtgc aagattgggc 300
tactatggta actacgagga ctggtatttc gatgtctggg gcgcagggac cacggtcacc 360
gtctcctctg ccaaaacgac acccccatct gtctatccac tggcccctgg atctgctgcc 420
caaactaact ccatggtgac cctgggatgc ctggtcaagg gctatttccc tgagccagtg 480
acagtgacct ggaactctgg atccctgtcc agcggtgtgc acaccttccc agctgtcctg 540
cagtctgacc tctacactct gagcagctca gtgactgtcc cctccagcac ctggcccagc 600
gagaccgtca cctgcaacgt tgcccacccg gccagcagca ccaaggtgga caagaaaatt 660
gtgcccaggg attgtggttg taagccttgc atatgtacag tcccagaagt atcatctgtc 720
ttcatcttcc ccccaaagcc caaggatgtg ctcaccatta ctctgactcc taaggtcacg 780
tgtgttgtgg tagacatcag caaggatgat cccgaggtcc agttcagctg gtttgtagat 840
gatgtggagg tgcacacagc tcagacgcaa ccccgggagg agcagttcaa cagcactttc 900
cgctcagtca gtgaacttcc catcatgcac caggactggc tcaatggcaa ggagttcaaa 960
tgcagggtca acagtgcagc tttccctgcc cccatcgaga aaaccatctc caaaaccaaa 1020
ggcagaccga aggctccaca ggtgtacacc attccacctc ccaaggagca gatggccaag 1080
gataaagtca gtctgacctg catgataaca gacttcttcc ctgaagacat tactgtggag 1140
tggcagtgga atgggcagcc agcggagaac tacaagaaca ctcagcccat catggacaca 1200
gatggctctt acttcatcta cagcaagctc aatgtgcaga agagcaactg ggaggcagga 1260
aatactttca cctgctctgt gttacatgag ggcctgcaca accaccatac tgagaagagc 1320
ctctcccact ctcctggtaa atga 1344
<210> 203
<211> 466
<212> PRT
<213> 家鼷鼠
<400> 203
Met Gly Trp Ser Trp Thr Phe Leu Phe Leu Leu Ser Gly Thr Ser Gly
1 5 10 15
Val Leu Ser Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Met Lys
20 25 30
Pro Gly Ala Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe
35 40 45
Thr Asp Tyr Asn Met His Trp Met Lys Gln Asn Gln Gly Lys Ser Leu
50 55 60
Glu Trp Ile Gly Glu Ile Asn Pro Asn Ser Gly Gly Ser Gly 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 Ser Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Leu Gly Tyr Tyr Gly Asn Tyr Glu Asp Trp Tyr
115 120 125
Phe Asp Val Trp Gly Ala Gly Thr Thr Val Thr Val Ser Ser Ala Lys
130 135 140
Thr Thr Pro Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln
145 150 155 160
Thr Asn Ser Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro
165 170 175
Glu Pro Val Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val
180 185 190
His Thr Phe Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser
195 200 205
Ser Val Thr Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val Thr Cys
210 215 220
Asn Val Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val
225 230 235 240
Pro Arg Asp Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val
245 250 255
Ser Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile
260 265 270
Thr Leu Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp
275 280 285
Asp Pro Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His
290 295 300
Thr Ala Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg
305 310 315 320
Ser Val Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys
325 330 335
Glu Phe Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu
340 345 350
Lys Thr Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr
355 360 365
Thr Ile Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu
370 375 380
Thr Cys Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp
385 390 395 400
Gln Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile
405 410 415
Met Asp Thr Asp Gly Ser Tyr Phe Ile Tyr Ser Lys Leu Asn Val Gln
420 425 430
Lys Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His
435 440 445
Glu Gly Leu His Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro
450 455 460
Gly Lys
465
<210> 204
<211> 1401
<212> DNA
<213> 家鼷鼠
<400> 204
atgggatgga gctggacctt tctcttcctc ctgtcaggaa cttcgggtgt cctctctgag 60
gtccagttgc aacagtctgg acctgaacta atgaagcctg gggcttcagt gaagatgtcc 120
tgcaaggctt ctggatacac attcactgac tacaacatgc actggatgaa gcagaaccaa 180
ggaaagagcc tagagtggat aggagagatt aatcctaaca gtggtggttc tggttacaac 240
cagaagttca aaggcaaggc cacattgact gtagacaagt cctccagcac agcctacatg 300
gagctccgca gcctgacatc tgaggactct gcagtctatt actgtgcaag attgggctac 360
tatggtaact acgaggactg gtatttcgat gtctggggcg cagggaccac ggtcaccgtc 420
tcctctgcca aaacgacacc cccatctgtc tatccactgg cccctggatc tgctgcccaa 480
actaactcca tggtgaccct gggatgcctg gtcaagggct atttccctga gccagtgaca 540
gtgacctgga actctggatc cctgtccagc ggtgtgcaca ccttcccagc tgtcctgcag 600
tctgacctct acactctgag cagctcagtg actgtcccct ccagcacctg gcccagcgag 660
accgtcacct gcaacgttgc ccacccggcc agcagcacca aggtggacaa gaaaattgtg 720
cccagggatt gtggttgtaa gccttgcata tgtacagtcc cagaagtatc atctgtcttc 780
atcttccccc caaagcccaa ggatgtgctc accattactc tgactcctaa ggtcacgtgt 840
gttgtggtag acatcagcaa ggatgatccc gaggtccagt tcagctggtt tgtagatgat 900
gtggaggtgc acacagctca gacgcaaccc cgggaggagc agttcaacag cactttccgc 960
tcagtcagtg aacttcccat catgcaccag gactggctca atggcaagga gttcaaatgc 1020
agggtcaaca gtgcagcttt ccctgccccc atcgagaaaa ccatctccaa aaccaaaggc 1080
agaccgaagg ctccacaggt gtacaccatt ccacctccca aggagcagat ggccaaggat 1140
aaagtcagtc tgacctgcat gataacagac ttcttccctg aagacattac tgtggagtgg 1200
cagtggaatg ggcagccagc ggagaactac aagaacactc agcccatcat ggacacagat 1260
ggctcttact tcatctacag caagctcaat gtgcagaaga gcaactggga ggcaggaaat 1320
actttcacct gctctgtgtt acatgagggc ctgcacaacc accatactga gaagagcctc 1380
tcccactctc ctggtaaatg a 1401
<210> 205
<211> 215
<212> PRT
<213> 家鼷鼠
<400> 205
Gln Ile Val Leu Thr Gln Ser Pro Ala Ile Met Ser Ala Ser Pro Gly
1 5 10 15
Glu Lys Val Thr Met Thr Cys Arg Ala Ser Ser Ser Val Thr Ser Ser
20 25 30
Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Ser Ser Pro Lys Leu Trp
35 40 45
Ile Tyr Ser Thr Ser Asn Leu Ala Ser Gly Val Pro Ala Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile Ser Ser Val Glu
65 70 75 80
Ala Glu Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Tyr Asp Phe Phe Pro
85 90 95
Ser Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Ala Asp Ala
100 105 110
Ala Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln Leu Thr Ser
115 120 125
Gly Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr Pro Lys Asp
130 135 140
Ile Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln Asn Gly Val
145 150 155 160
Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr Tyr Ser Met
165 170 175
Ser Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg His Asn Ser
180 185 190
Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro Ile Val Lys
195 200 205
Ser Phe Asn Arg Asn Glu Cys
210 215
<210> 206
<211> 645
<212> DNA
<213> 家鼷鼠
<400> 206
cagattgttc tcacccagtc tccagcaatc atgtctgcat ctccagggga gaaggtcacc 60
atgacctgca gggccagctc aagtgtaact tccagttact tgaactggta ccagcagaag 120
ccaggatctt cccccaaact ctggatttat agcacatcca acctggcttc aggagtccca 180
gctcgcttca gtggcagtgg gtctgggacc tcttactctc tcacaatcag cagtgtggag 240
gctgaggatg ctgccactta ttactgccag cagtatgatt ttttcccatc gacgttcggt 300
ggaggcacca agctggaaat caagcgggct gatgctgcac caactgtatc catcttccca 360
ccatccagtg agcagttaac atctggaggt gcctcagtcg tgtgcttctt gaacaacttc 420
taccccaaag acatcaatgt caagtggaag attgatggca gtgaacgaca aaatggcgtc 480
ctgaacagtt ggactgatca ggacagcaaa gacagcacct acagcatgag cagcaccctc 540
acgttgacca aggacgagta tgaacgacat aacagctata cctgtgaggc cactcacaag 600
acatcaactt cacccatcgt caagagcttc aacaggaatg agtgt 645
<210> 207
<211> 237
<212> PRT
<213> 家鼷鼠
<400> 207
Met Asp Ser Gln Val Gln Ile Phe Ser Phe Leu Leu Ile Ser Ala Leu
1 5 10 15
Val Lys Met Ser Arg Gly Gln Ile Val Leu Thr Gln Ser Pro Ala Ile
20 25 30
Met Ser Ala Ser Pro Gly Glu Lys Val Thr Met Thr Cys Arg Ala Ser
35 40 45
Ser Ser Val Thr Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly
50 55 60
Ser Ser Pro Lys Leu Trp Ile Tyr Ser Thr Ser Asn Leu Ala Ser Gly
65 70 75 80
Val Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Ser Tyr Ser Leu
85 90 95
Thr Ile Ser Ser Val Glu Ala Glu Asp Ala Ala Thr Tyr Tyr Cys Gln
100 105 110
Gln Tyr Asp Phe Phe Pro Ser Thr Phe Gly Gly Gly Thr Lys Leu Glu
115 120 125
Ile Lys Arg Ala Asp Ala Ala Pro Thr Val Ser Ile Phe Pro Pro Ser
130 135 140
Ser Glu Gln Leu Thr Ser Gly Gly Ala Ser Val Val Cys Phe Leu Asn
145 150 155 160
Asn Phe Tyr Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly Ser
165 170 175
Glu Arg Gln Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys
180 185 190
Asp Ser Thr Tyr Ser Met Ser Ser Thr Leu Thr Leu Thr Lys Asp Glu
195 200 205
Tyr Glu Arg His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr Ser
210 215 220
Thr Ser Pro Ile Val Lys Ser Phe Asn Arg Asn Glu Cys
225 230 235
<210> 208
<211> 711
<212> DNA
<213> 家鼷鼠
<400> 208
atggattctc aagtgcagat tttcagcttc cttctaatca gtgccttagt caaaatgtcc 60
agaggacaga ttgttctcac ccagtctcca gcaatcatgt ctgcatctcc aggggagaag 120
gtcaccatga cctgcagggc cagctcaagt gtaacttcca gttacttgaa ctggtaccag 180
cagaagccag gatcttcccc caaactctgg atttatagca catccaacct ggcttcagga 240
gtcccagctc gcttcagtgg cagtgggtct gggacctctt actctctcac aatcagcagt 300
gtggaggctg aggatgctgc cacttattac tgccagcagt atgatttttt cccatcgacg 360
ttcggtggag gcaccaagct ggaaatcaag cgggctgatg ctgcaccaac tgtatccatc 420
ttcccaccat ccagtgagca gttaacatct ggaggtgcct cagtcgtgtg cttcttgaac 480
aacttctacc ccaaagacat caatgtcaag tggaagattg atggcagtga acgacaaaat 540
ggcgtcctga acagttggac tgatcaggac agcaaagaca gcacctacag catgagcagc 600
accctcacgt tgaccaagga cgagtatgaa cgacataaca gctatacctg tgaggccact 660
cacaagacat caacttcacc catcgtcaag agcttcaaca ggaatgagtg t 711
<210> 209
<211> 445
<212> PRT
<213> 家鼷鼠
<400> 209
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Tyr Met Asn Trp Val Lys Gln Ser His Gly Glu Ser Leu Glu Trp Ile
35 40 45
Gly Asp Ile Asn Pro Tyr Asn Asp Asp Thr Thr Tyr Asn His Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Asn Thr Ala Tyr
65 70 75 80
Met Gln Leu Asn Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Thr Ala Val Ile Thr Thr Asn Ala Met Asp Tyr Trp Gly
100 105 110
Gln Gly Thr Ser Val Thr Val Ser Ser Ala Lys Thr Thr Pro Pro Ser
115 120 125
Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr Asn Ser Met Val
130 135 140
Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val Thr Val
145 150 155 160
Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr Phe Pro Ala
165 170 175
Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr Val Pro
180 185 190
Ser Ser Thr Trp Pro Ser Glu Thr Val Thr Cys Asn Val Ala His Pro
195 200 205
Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val Pro Arg Asp Cys Gly
210 215 220
Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser Ser Val Phe Ile
225 230 235 240
Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro Lys
245 250 255
Val Thr Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu Val Gln
260 265 270
Phe Ser Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr Gln
275 280 285
Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser Glu Leu
290 295 300
Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg
305 310 315 320
Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys
325 330 335
Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro
340 345 350
Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile Thr
355 360 365
Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly Gln
370 375 380
Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr Asp Gly
385 390 395 400
Ser Tyr Phe Ile Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn Trp Glu
405 410 415
Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His Asn
420 425 430
His His Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys
435 440 445
<210> 210
<211> 1335
<212> DNA
<213> 家鼷鼠
<400> 210
gaggtccagc tgcaacaatc tggacctgag ctggtgaagc ctggggcttc agtgaagatg 60
tcctgtaagg cttctggata cacattcact gactactaca tgaactgggt gaagcagagc 120
catggagaga gccttgagtg gattggagat attaatcctt acaacgatga tactacctac 180
aaccacaagt tcaagggcaa ggccacattg actgtagaca aatcctccaa cacagcctac 240
atgcagctca acagcctgac atctgaggac tctgcagtct attactgtgc aagagagacg 300
gccgttatta ctacgaatgc tatggactac tggggtcaag gaacctcagt caccgtctcc 360
tcagccaaaa cgacaccccc atctgtctat ccactggccc ctggatctgc tgcccaaact 420
aactccatgg tgaccctggg atgcctggtc aagggctatt tccctgagcc agtgacagtg 480
acctggaact ctggatccct gtccagcggt gtgcacacct tcccagctgt cctgcagtct 540
gacctctaca ctctgagcag ctcagtgact gtcccctcca gcacctggcc cagcgagacc 600
gtcacctgca acgttgccca cccggccagc agcaccaagg tggacaagaa aattgtgccc 660
agggattgtg gttgtaagcc ttgcatatgt acagtcccag aagtatcatc tgtcttcatc 720
ttccccccaa agcccaagga tgtgctcacc attactctga ctcctaaggt cacgtgtgtt 780
gtggtagaca tcagcaagga tgatcccgag gtccagttca gctggtttgt agatgatgtg 840
gaggtgcaca cagctcagac gcaaccccgg gaggagcagt tcaacagcac tttccgctca 900
gtcagtgaac ttcccatcat gcaccaggac tggctcaatg gcaaggagtt caaatgcagg 960
gtcaacagtg cagctttccc tgcccccatc gagaaaacca tctccaaaac caaaggcaga 1020
ccgaaggctc cacaggtgta caccattcca cctcccaagg agcagatggc caaggataaa 1080
gtcagtctga cctgcatgat aacagacttc ttccctgaag acattactgt ggagtggcag 1140
tggaatgggc agccagcgga gaactacaag aacactcagc ccatcatgga cacagatggc 1200
tcttacttca tctacagcaa gctcaatgtg cagaagagca actgggaggc aggaaatact 1260
ttcacctgct ctgtgttaca tgagggcctg cacaaccacc atactgagaa gagcctctcc 1320
cactctcctg gtaaa 1335
<210> 211
<211> 464
<212> PRT
<213> 家鼷鼠
<400> 211
Met Gly Trp Asn Trp Ile Phe Leu Phe Leu Leu Ser Gly Thr Ala Gly
1 5 10 15
Val Tyr Ser Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys
20 25 30
Pro Gly Ala Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe
35 40 45
Thr Asp Tyr Tyr Met Asn Trp Val Lys Gln Ser His Gly Glu Ser Leu
50 55 60
Glu Trp Ile Gly Asp Ile Asn Pro Tyr Asn Asp Asp Thr Thr Tyr Asn
65 70 75 80
His Lys Phe Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Asn
85 90 95
Thr Ala Tyr Met Gln Leu Asn Ser Leu Thr Ser Glu Asp Ser Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Glu Thr Ala Val Ile Thr Thr Asn Ala Met Asp
115 120 125
Tyr Trp Gly Gln Gly Thr Ser Val Thr Val Ser Ser Ala Lys Thr Thr
130 135 140
Pro Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr Asn
145 150 155 160
Ser Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro
165 170 175
Val Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr
180 185 190
Phe Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val
195 200 205
Thr Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val Thr Cys Asn Val
210 215 220
Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val Pro Arg
225 230 235 240
Asp Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser Ser
245 250 255
Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu
260 265 270
Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro
275 280 285
Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His Thr Ala
290 295 300
Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val
305 310 315 320
Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe
325 330 335
Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr
340 345 350
Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile
355 360 365
Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys
370 375 380
Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp
385 390 395 400
Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp
405 410 415
Thr Asp Gly Ser Tyr Phe Ile Tyr Ser Lys Leu Asn Val Gln Lys Ser
420 425 430
Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly
435 440 445
Leu His Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys
450 455 460
<210> 212
<211> 1392
<212> DNA
<213> 家鼷鼠
<400> 212
atgggatgga actggatctt tctcttcctc ttgtcaggaa ctgcaggtgt ctactctgag 60
gtccagctgc aacaatctgg acctgagctg gtgaagcctg gggcttcagt gaagatgtcc 120
tgtaaggctt ctggatacac attcactgac tactacatga actgggtgaa gcagagccat 180
ggagagagcc ttgagtggat tggagatatt aatccttaca acgatgatac tacctacaac 240
cacaagttca agggcaaggc cacattgact gtagacaaat cctccaacac agcctacatg 300
cagctcaaca gcctgacatc tgaggactct gcagtctatt actgtgcaag agagacggcc 360
gttattacta cgaatgctat ggactactgg ggtcaaggaa cctcagtcac cgtctcctca 420
gccaaaacga cacccccatc tgtctatcca ctggcccctg gatctgctgc ccaaactaac 480
tccatggtga ccctgggatg cctggtcaag ggctatttcc ctgagccagt gacagtgacc 540
tggaactctg gatccctgtc cagcggtgtg cacaccttcc cagctgtcct gcagtctgac 600
ctctacactc tgagcagctc agtgactgtc ccctccagca cctggcccag cgagaccgtc 660
acctgcaacg ttgcccaccc ggccagcagc accaaggtgg acaagaaaat tgtgcccagg 720
gattgtggtt gtaagccttg catatgtaca gtcccagaag tatcatctgt cttcatcttc 780
cccccaaagc ccaaggatgt gctcaccatt actctgactc ctaaggtcac gtgtgttgtg 840
gtagacatca gcaaggatga tcccgaggtc cagttcagct ggtttgtaga tgatgtggag 900
gtgcacacag ctcagacgca accccgggag gagcagttca acagcacttt ccgctcagtc 960
agtgaacttc ccatcatgca ccaggactgg ctcaatggca aggagttcaa atgcagggtc 1020
aacagtgcag ctttccctgc ccccatcgag aaaaccatct ccaaaaccaa aggcagaccg 1080
aaggctccac aggtgtacac cattccacct cccaaggagc agatggccaa ggataaagtc 1140
agtctgacct gcatgataac agacttcttc cctgaagaca ttactgtgga gtggcagtgg 1200
aatgggcagc cagcggagaa ctacaagaac actcagccca tcatggacac agatggctct 1260
tacttcatct acagcaagct caatgtgcag aagagcaact gggaggcagg aaatactttc 1320
acctgctctg tgttacatga gggcctgcac aaccaccata ctgagaagag cctctcccac 1380
tctcctggta aa 1392
<210> 213
<211> 215
<212> PRT
<213> 人工序列
<220>
<223> 合成多肽
<220>
<221> MISC_FEATURE
<223> 人源化抗体序列
<400> 213
Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Ser Ser Val Thr Ser Ser
20 25 30
Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu
35 40 45
Ile Tyr Ser Thr Ser Asn Leu Ala Ser Gly Val Pro 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
Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Asp Phe Phe Pro
85 90 95
Ser Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala
100 105 110
Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser
115 120 125
Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu
130 135 140
Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser
145 150 155 160
Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu
165 170 175
Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val
180 185 190
Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys
195 200 205
Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 214
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成多核苷酸
<220>
<221> misc_feature
<223> 人源化抗体序列
<400> 214
gacatccagc tgacccagag ccccagcttc ctttccgcat ccgttggtga ccgagtaaca 60
atcacatgcc gcgcctcatc ttcagttaca tcttcttatc ttaattggta tcaacaaaaa 120
ccaggaaaag cacctaaact tcttatatac tctacatcta atctcgcatc aggagttccc 180
tctcgatttt caggatctgg atcaggcaca gaatttacac ttactatatc atcactccaa 240
ccagaagact tcgccactta ttactgccaa caatacgatt tttttccaag cacattcgga 300
ggaggtacaa aagtagaaat caagcgtacg gtggctgcac catctgtctt catcttcccg 360
ccatctgatg agcagttgaa atctggaact gcctctgttg tgtgcctgct gaataacttc 420
tatcccagag aggccaaagt acagtggaag gtggataacg ccctccaatc gggtaactcc 480
caggagagtg tcacagagca ggacagcaag gacagcacct acagcctcag cagcaccctg 540
acgctgagca aagcagacta cgagaaacac aaagtctacg cctgcgaagt cacccatcag 600
ggcctgagct cgcccgtcac aaagagcttc aacaggggag agtgt 645
<210> 215
<211> 237
<212> PRT
<213> 人工序列
<220>
<223> 合成多肽
<220>
<221> MISC_FEATURE
<223> 人源化抗体序列
<400> 215
Met Asp Met Arg Val Pro Ala Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Arg Cys Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe
20 25 30
Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser
35 40 45
Ser Ser Val Thr Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly
50 55 60
Lys Ala Pro Lys Leu Leu Ile Tyr Ser Thr Ser Asn Leu Ala Ser Gly
65 70 75 80
Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu
85 90 95
Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln
100 105 110
Gln Tyr Asp Phe Phe Pro Ser Thr Phe Gly Gly Gly Thr Lys Val Glu
115 120 125
Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser
130 135 140
Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn
145 150 155 160
Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala
165 170 175
Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys
180 185 190
Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp
195 200 205
Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu
210 215 220
Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
225 230 235
<210> 216
<211> 711
<212> DNA
<213> 人工序列
<220>
<223> 合成多核苷酸
<220>
<221> misc_feature
<223> 人源化抗体序列
<400> 216
atggacatga gggtccccgc tcagctcctg gggctcctgc tactctggct cccaggtgcc 60
agatgtgaca tccagctgac ccagagcccc agcttccttt ccgcatccgt tggtgaccga 120
gtaacaatca catgccgcgc ctcatcttca gttacatctt cttatcttaa ttggtatcaa 180
caaaaaccag gaaaagcacc taaacttctt atatactcta catctaatct cgcatcagga 240
gttccctctc gattttcagg atctggatca ggcacagaat ttacacttac tatatcatca 300
ctccaaccag aagacttcgc cacttattac tgccaacaat acgatttttt tccaagcaca 360
ttcggaggag gtacaaaagt agaaatcaag cgtacggtgg ctgcaccatc tgtcttcatc 420
ttcccgccat ctgatgagca gttgaaatct ggaactgcct ctgttgtgtg cctgctgaat 480
aacttctatc ccagagaggc caaagtacag tggaaggtgg ataacgccct ccaatcgggt 540
aactcccagg agagtgtcac agagcaggac agcaaggaca gcacctacag cctcagcagc 600
accctgacgc tgagcaaagc agactacgag aaacacaaag tctacgcctg cgaagtcacc 660
catcagggcc tgagctcgcc cgtcacaaag agcttcaaca ggggagagtg t 711
<210> 217
<211> 447
<212> PRT
<213> 人工序列
<220>
<223> 合成多肽
<220>
<221> MISC_FEATURE
<223> 人源化抗体序列
<400> 217
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Tyr Met Asn Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Met
35 40 45
Gly Asp Ile Asn Pro Tyr Asn Asp Asp Thr Thr Tyr Asn His Lys Phe
50 55 60
Lys Gly Arg Val Thr Ile Thr Arg Asp Thr Ser Ala Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Thr Ala Val Ile Thr Thr Asn Ala Met Asp Tyr Trp Gly
100 105 110
Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser
115 120 125
Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala
130 135 140
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val
145 150 155 160
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala
165 170 175
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val
180 185 190
Pro Ser Ser Asn Phe Gly Thr Gln Thr Tyr Thr Cys Asn Val Asp His
195 200 205
Lys Pro Ser Asn Thr Lys Val Asp Lys Thr Val Glu Arg Lys Cys Cys
210 215 220
Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val
225 230 235 240
Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr
245 250 255
Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu
260 265 270
Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys
275 280 285
Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Val Val Ser
290 295 300
Val Leu Thr Val Val His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys
305 310 315 320
Cys Lys Val Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu Lys Thr Ile
325 330 335
Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro
340 345 350
Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu
355 360 365
Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn
370 375 380
Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Met Leu Asp Ser
385 390 395 400
Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg
405 410 415
Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu
420 425 430
His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440 445
<210> 218
<211> 1341
<212> DNA
<213> 人工序列
<220>
<223> 合成多核苷酸
<220>
<221> misc_feature
<223> 人源化抗体序列
<400> 218
gaggtgcagc tggtgcagag cggcgccgag gtcaagaaac ctggagcaag cgtaaaggtt 60
agttgcaaag catctggata cacatttacc gactactaca tgaattgggt acgacaagcc 120
cctggacaaa gacttgaatg gatgggagac attaaccctt ataacgacga cactacatac 180
aatcataaat ttaaaggaag agttacaatt acaagagata catccgcatc aaccgcctat 240
atggaacttt cctcattgag atctgaagac actgctgttt attactgtgc aagagaaact 300
gccgttatta ctactaacgc tatggattac tggggtcaag gaaccactgt taccgtctct 360
agtgcctcca ccaagggccc atcggtcttc cccctggcgc cctgctccag gagcacctcc 420
gagagcacag cggccctggg ctgcctggtc aaggactact tccccgaacc ggtgacggtg 480
tcgtggaact caggcgctct gaccagcggc gtgcacacct tcccagctgt cctacagtcc 540
tcaggactct actccctcag cagcgtggtg accgtgccct ccagcaactt cggcacccag 600
acctacacct gcaacgtaga tcacaagccc agcaacacca aggtggacaa gacagttgag 660
cgcaaatgtt gtgtcgagtg cccaccgtgc ccagcaccac ctgtggcagg accgtcagtc 720
ttcctcttcc ccccaaaacc caaggacacc ctcatgatct cccggacccc tgaggtcacg 780
tgcgtggtgg tggacgtgag ccacgaagac cccgaggtcc agttcaactg gtacgtggac 840
ggcgtggagg tgcataatgc caagacaaag ccacgggagg agcagttcaa cagcacgttc 900
cgtgtggtca gcgtcctcac cgttgtgcac caggactggc tgaacggcaa ggagtacaag 960
tgcaaggtct ccaacaaagg cctcccagcc cccatcgaga aaaccatctc caaaaccaaa 1020
gggcagcccc gagaaccaca ggtgtacacc ctgcccccat cccgggagga gatgaccaag 1080
aaccaggtca gcctgacctg cctggtcaaa ggcttctacc ccagcgacat cgccgtggag 1140
tgggagagca atgggcagcc ggagaacaac tacaagacca cacctcccat gctggactcc 1200
gacggctcct tcttcctcta cagcaagctc accgtggaca agagcaggtg gcagcagggg 1260
aacgtcttct catgctccgt gatgcatgag gctctgcaca accactacac gcagaagagc 1320
ctctccctgt ctccgggtaa a 1341
<210> 219
<211> 466
<212> PRT
<213> 人工序列
<220>
<223> 合成多肽
<220>
<221> MISC_FEATURE
<223> 人源化抗体序列
<400> 219
Met Asp Trp Thr Trp Arg Ile Leu Phe Leu Val Ala Ala Ala Thr Gly
1 5 10 15
Ala His Ser Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys
20 25 30
Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe
35 40 45
Thr Asp Tyr Tyr Met Asn Trp Val Arg Gln Ala Pro Gly Gln Arg Leu
50 55 60
Glu Trp Met Gly Asp Ile Asn Pro Tyr Asn Asp Asp Thr Thr Tyr Asn
65 70 75 80
His Lys Phe Lys Gly Arg Val Thr Ile Thr Arg Asp Thr Ser Ala Ser
85 90 95
Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Glu Thr Ala Val Ile Thr Thr Asn Ala Met Asp
115 120 125
Tyr Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys
130 135 140
Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu
145 150 155 160
Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro
165 170 175
Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr
180 185 190
Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val
195 200 205
Val Thr Val Pro Ser Ser Asn Phe Gly Thr Gln Thr Tyr Thr Cys Asn
210 215 220
Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Thr Val Glu Arg
225 230 235 240
Lys Cys Cys Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly
245 250 255
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
260 265 270
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
275 280 285
Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
290 295 300
Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg
305 310 315 320
Val Val Ser Val Leu Thr Val Val His Gln Asp Trp Leu Asn Gly Lys
325 330 335
Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu
340 345 350
Lys Thr Ile Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
355 360 365
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
370 375 380
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
385 390 395 400
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Met
405 410 415
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
420 425 430
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
435 440 445
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
450 455 460
Gly Lys
465
<210> 220
<211> 1398
<212> DNA
<213> 人工序列
<220>
<223> 合成多核苷酸
<220>
<221> misc_feature
<223> 人源化抗体序列
<400> 220
atggactgga cctggaggat cctcttcttg gtggcagcag ccacaggagc ccactccgag 60
gtgcagctgg tgcagagcgg cgccgaggtc aagaaacctg gagcaagcgt aaaggttagt 120
tgcaaagcat ctggatacac atttaccgac tactacatga attgggtacg acaagcccct 180
ggacaaagac ttgaatggat gggagacatt aacccttata acgacgacac tacatacaat 240
cataaattta aaggaagagt tacaattaca agagatacat ccgcatcaac cgcctatatg 300
gaactttcct cattgagatc tgaagacact gctgtttatt actgtgcaag agaaactgcc 360
gttattacta ctaacgctat ggattactgg ggtcaaggaa ccactgttac cgtctctagt 420
gcctccacca agggcccatc ggtcttcccc ctggcgccct gctccaggag cacctccgag 480
agcacagcgg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg 540
tggaactcag gcgctctgac cagcggcgtg cacaccttcc cagctgtcct acagtcctca 600
ggactctact ccctcagcag cgtggtgacc gtgccctcca gcaacttcgg cacccagacc 660
tacacctgca acgtagatca caagcccagc aacaccaagg tggacaagac agttgagcgc 720
aaatgttgtg tcgagtgccc accgtgccca gcaccacctg tggcaggacc gtcagtcttc 780
ctcttccccc caaaacccaa ggacaccctc atgatctccc ggacccctga ggtcacgtgc 840
gtggtggtgg acgtgagcca cgaagacccc gaggtccagt tcaactggta cgtggacggc 900
gtggaggtgc ataatgccaa gacaaagcca cgggaggagc agttcaacag cacgttccgt 960
gtggtcagcg tcctcaccgt tgtgcaccag gactggctga acggcaagga gtacaagtgc 1020
aaggtctcca acaaaggcct cccagccccc atcgagaaaa ccatctccaa aaccaaaggg 1080
cagccccgag aaccacaggt gtacaccctg cccccatccc gggaggagat gaccaagaac 1140
caggtcagcc tgacctgcct ggtcaaaggc ttctacccca gcgacatcgc cgtggagtgg 1200
gagagcaatg ggcagccgga gaacaactac aagaccacac ctcccatgct ggactccgac 1260
ggctccttct tcctctacag caagctcacc gtggacaaga gcaggtggca gcaggggaac 1320
gtcttctcat gctccgtgat gcatgaggct ctgcacaacc actacacgca gaagagcctc 1380
tccctgtctc cgggtaaa 1398
<210> 221
<211> 215
<212> PRT
<213> 人工序列
<220>
<223> 合成多肽
<220>
<221> MISC_FEATURE
<223> 人源化抗体序列
<400> 221
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Ser Val Ser Ser Thr Ile Ser Ser Asn
20 25 30
His Leu His Trp Phe Gln Gln Lys Pro Gly Lys Ala Pro Lys Ser Leu
35 40 45
Ile Tyr Gly Thr Ser Asn Leu Ala Ser Gly Val Pro Ser Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln
65 70 75 80
Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Trp Ser Ser Tyr Pro
85 90 95
Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala
100 105 110
Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser
115 120 125
Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu
130 135 140
Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser
145 150 155 160
Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu
165 170 175
Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val
180 185 190
Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys
195 200 205
Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 222
<211> 645
<212> DNA
<213> 人工序列
<220>
<223> 合成多核苷酸
<220>
<221> misc_feature
<223> 人源化抗体序列
<400> 222
gacatccaga tgacccagtc tccatcctcc ctctcagcat ccgtaggcga tagagttaca 60
ataacatgca gcgtatcatc aactatatca tcaaatcatc ttcattggtt ccaacagaaa 120
cccggcaaag cacctaaatc acttatatac ggcacatcaa atctcgcatc aggcgttcct 180
tcaagatttt caggctctgg ctcaggcacc gactttactc ttacaatatc ctccctccaa 240
cccgaagact tcgcaaccta ttactgtcaa caatggtcct catatccact cacatttggc 300
ggcggcacaa aagtagaaat taaacgtacg gtggctgcac catctgtctt catcttcccg 360
ccatctgatg agcagttgaa atctggaact gcctctgttg tgtgcctgct gaataacttc 420
tatcccagag aggccaaagt acagtggaag gtggataacg ccctccaatc gggtaactcc 480
caggagagtg tcacagagca ggacagcaag gacagcacct acagcctcag cagcaccctg 540
acgctgagca aagcagacta cgagaaacac aaagtctacg cctgcgaagt cacccatcag 600
ggcctgagct cgcccgtcac aaagagcttc aacaggggag agtgt 645
<210> 223
<211> 237
<212> PRT
<213> 人工序列
<220>
<223> 合成多肽
<220>
<221> MISC_FEATURE
<223> 人源化抗体序列
<400> 223
Met Asp Met Arg Val Pro Ala Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Arg Gly Ala Arg Cys Asp Ile Gln Met Thr Gln Ser Pro Ser Ser
20 25 30
Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Ser Val Ser
35 40 45
Ser Thr Ile Ser Ser Asn His Leu His Trp Phe Gln Gln Lys Pro Gly
50 55 60
Lys Ala Pro Lys Ser Leu Ile Tyr Gly Thr Ser Asn Leu Ala Ser Gly
65 70 75 80
Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu
85 90 95
Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln
100 105 110
Gln Trp Ser Ser Tyr Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu
115 120 125
Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser
130 135 140
Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn
145 150 155 160
Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala
165 170 175
Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys
180 185 190
Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp
195 200 205
Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu
210 215 220
Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
225 230 235
<210> 224
<211> 711
<212> DNA
<213> 人工序列
<220>
<223> 合成多核苷酸
<220>
<221> misc_feature
<223> 人源化抗体序列
<400> 224
atggacatga gggtccccgc tcagctcctg gggctcctgc tactctggct ccgaggtgcc 60
agatgtgaca tccagatgac ccagtctcca tcctccctct cagcatccgt aggcgataga 120
gttacaataa catgcagcgt atcatcaact atatcatcaa atcatcttca ttggttccaa 180
cagaaacccg gcaaagcacc taaatcactt atatacggca catcaaatct cgcatcaggc 240
gttccttcaa gattttcagg ctctggctca ggcaccgact ttactcttac aatatcctcc 300
ctccaacccg aagacttcgc aacctattac tgtcaacaat ggtcctcata tccactcaca 360
tttggcggcg gcacaaaagt agaaattaaa cgtacggtgg ctgcaccatc tgtcttcatc 420
ttcccgccat ctgatgagca gttgaaatct ggaactgcct ctgttgtgtg cctgctgaat 480
aacttctatc ccagagaggc caaagtacag tggaaggtgg ataacgccct ccaatcgggt 540
aactcccagg agagtgtcac agagcaggac agcaaggaca gcacctacag cctcagcagc 600
accctgacgc tgagcaaagc agactacgag aaacacaaag tctacgcctg cgaagtcacc 660
catcagggcc tgagctcgcc cgtcacaaag agcttcaaca ggggagagtg t 711
<210> 225
<211> 451
<212> PRT
<213> 人工序列
<220>
<223> 合成多肽
<220>
<221> MISC_FEATURE
<223> 人源化抗体序列
<400> 225
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Asp Phe Asn Ile Lys Asp Phe
20 25 30
Tyr Leu His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Arg Ile Asp Pro Glu Asn Gly Asp Thr Leu Tyr Asp Pro Lys Phe
50 55 60
Gln Asp Lys Val Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Ala Asp Tyr Phe His Asp Gly Thr Ser Tyr Trp Tyr Phe
100 105 110
Asp Val Trp Gly Arg Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr
115 120 125
Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser
130 135 140
Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu
145 150 155 160
Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His
165 170 175
Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser
180 185 190
Val Val Thr Val Pro Ser Ser Asn Phe Gly Thr Gln Thr Tyr Thr Cys
195 200 205
Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Thr Val Glu
210 215 220
Arg Lys Cys Cys Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val Ala
225 230 235 240
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
245 250 255
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
260 265 270
Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val
275 280 285
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe
290 295 300
Arg Val Val Ser Val Leu Thr Val Val His Gln Asp Trp Leu Asn Gly
305 310 315 320
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ala Pro Ile
325 330 335
Glu Lys Thr Ile Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln Val
340 345 350
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
355 360 365
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
370 375 380
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
385 390 395 400
Met Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
405 410 415
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
420 425 430
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
435 440 445
Pro Gly Lys
450
<210> 226
<211> 1353
<212> DNA
<213> 人工序列
<220>
<223> 合成多核苷酸
<400> 226
gaggtgcagc tggtgcagtc tggggctgag gtgaagaagc ctggggcctc agtgaaggtc 60
tcctgcaagg cttctgactt caacattaaa gacttctatc tacactgggt gcgacaggcc 120
cctggacaag ggcttgagtg gattggaagg attgatcctg agaatggtga tactttatat 180
gacccgaagt tccaggacaa ggtcaccatg accacagaca cgtccaccag cacagcctac 240
atggagctga ggagcctgag atctgacgac acggccgtgt attactgtgc gagagaggcg 300
gattatttcc acgatggtac ctcctactgg tacttcgatg tctggggccg tggcaccctg 360
gtcaccgtct ctagtgcctc caccaagggc ccatcggtct tccccctggc gccctgctcc 420
aggagcacct ccgagagcac agcggccctg ggctgcctgg tcaaggacta cttccccgaa 480
ccggtgacgg tgtcgtggaa ctcaggcgct ctgaccagcg gcgtgcacac cttcccagct 540
gtcctacagt cctcaggact ctactccctc agcagcgtgg tgaccgtgcc ctccagcaac 600
ttcggcaccc agacctacac ctgcaacgta gatcacaagc ccagcaacac caaggtggac 660
aagacagttg agcgcaaatg ttgtgtcgag tgcccaccgt gcccagcacc acctgtggca 720
ggaccgtcag tcttcctctt ccccccaaaa cccaaggaca ccctcatgat ctcccggacc 780
cctgaggtca cgtgcgtggt ggtggacgtg agccacgaag accccgaggt ccagttcaac 840
tggtacgtgg acggcgtgga ggtgcataat gccaagacaa agccacggga ggagcagttc 900
aacagcacgt tccgtgtggt cagcgtcctc accgttgtgc accaggactg gctgaacggc 960
aaggagtaca agtgcaaggt ctccaacaaa ggcctcccag cccccatcga gaaaaccatc 1020
tccaaaacca aagggcagcc ccgagaacca caggtgtaca ccctgccccc atcccgggag 1080
gagatgacca agaaccaggt cagcctgacc tgcctggtca aaggcttcta ccccagcgac 1140
atcgccgtgg agtgggagag caatgggcag ccggagaaca actacaagac cacacctccc 1200
atgctggact ccgacggctc cttcttcctc tacagcaagc tcaccgtgga caagagcagg 1260
tggcagcagg ggaacgtctt ctcatgctcc gtgatgcatg aggctctgca caaccactac 1320
acgcagaaga gcctctccct gtctccgggt aaa 1353
<210> 227
<211> 470
<212> PRT
<213> 人工序列
<220>
<223> 合成多肽
<220>
<221> MISC_FEATURE
<223> 人源化抗体序列
<400> 227
Met Asp Trp Thr Trp Arg Ile Leu Phe Leu Val Ala Ala Ala Thr Gly
1 5 10 15
Ala His Ser Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys
20 25 30
Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Asp Phe Asn Ile
35 40 45
Lys Asp Phe Tyr Leu His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu
50 55 60
Glu Trp Ile Gly Arg Ile Asp Pro Glu Asn Gly Asp Thr Leu Tyr Asp
65 70 75 80
Pro Lys Phe Gln Asp Lys Val Thr Met Thr Thr Asp Thr Ser Thr Ser
85 90 95
Thr Ala Tyr Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Glu Ala Asp Tyr Phe His Asp Gly Thr Ser Tyr
115 120 125
Trp Tyr Phe Asp Val Trp Gly Arg Gly Thr Leu Val Thr Val Ser Ser
130 135 140
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg
145 150 155 160
Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
165 170 175
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
180 185 190
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
195 200 205
Leu Ser Ser Val Val Thr Val Pro Ser Ser Asn Phe Gly Thr Gln Thr
210 215 220
Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys
225 230 235 240
Thr Val Glu Arg Lys Cys Cys Val Glu Cys Pro Pro Cys Pro Ala Pro
245 250 255
Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp
260 265 270
Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp
275 280 285
Val Ser His Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly
290 295 300
Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn
305 310 315 320
Ser Thr Phe Arg Val Val Ser Val Leu Thr Val Val His Gln Asp Trp
325 330 335
Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro
340 345 350
Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Gln Pro Arg Glu
355 360 365
Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn
370 375 380
Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile
385 390 395 400
Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr
405 410 415
Thr Pro Pro Met Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys
420 425 430
Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys
435 440 445
Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu
450 455 460
Ser Leu Ser Pro Gly Lys
465 470
<210> 228
<211> 1410
<212> DNA
<213> 人工序列
<220>
<223> 合成多核苷酸
<220>
<221> misc_feature
<223> 人源化抗体序列
<400> 228
atggactgga cctggaggat cctcttcttg gtggcagcag ccacaggagc ccactccgag 60
gtgcagctgg tgcagtctgg ggctgaggtg aagaagcctg gggcctcagt gaaggtctcc 120
tgcaaggctt ctgacttcaa cattaaagac ttctatctac actgggtgcg acaggcccct 180
ggacaagggc ttgagtggat tggaaggatt gatcctgaga atggtgatac tttatatgac 240
ccgaagttcc aggacaaggt caccatgacc acagacacgt ccaccagcac agcctacatg 300
gagctgagga gcctgagatc tgacgacacg gccgtgtatt actgtgcgag agaggcggat 360
tatttccacg atggtacctc ctactggtac ttcgatgtct ggggccgtgg caccctggtc 420
accgtctcta gtgcctccac caagggccca tcggtcttcc ccctggcgcc ctgctccagg 480
agcacctccg agagcacagc ggccctgggc tgcctggtca aggactactt ccccgaaccg 540
gtgacggtgt cgtggaactc aggcgctctg accagcggcg tgcacacctt cccagctgtc 600
ctacagtcct caggactcta ctccctcagc agcgtggtga ccgtgccctc cagcaacttc 660
ggcacccaga cctacacctg caacgtagat cacaagccca gcaacaccaa ggtggacaag 720
acagttgagc gcaaatgttg tgtcgagtgc ccaccgtgcc cagcaccacc tgtggcagga 780
ccgtcagtct tcctcttccc cccaaaaccc aaggacaccc tcatgatctc ccggacccct 840
gaggtcacgt gcgtggtggt ggacgtgagc cacgaagacc ccgaggtcca gttcaactgg 900
tacgtggacg gcgtggaggt gcataatgcc aagacaaagc cacgggagga gcagttcaac 960
agcacgttcc gtgtggtcag cgtcctcacc gttgtgcacc aggactggct gaacggcaag 1020
gagtacaagt gcaaggtctc caacaaaggc ctcccagccc ccatcgagaa aaccatctcc 1080
aaaaccaaag ggcagccccg agaaccacag gtgtacaccc tgcccccatc ccgggaggag 1140
atgaccaaga accaggtcag cctgacctgc ctggtcaaag gcttctaccc cagcgacatc 1200
gccgtggagt gggagagcaa tgggcagccg gagaacaact acaagaccac acctcccatg 1260
ctggactccg acggctcctt cttcctctac agcaagctca ccgtggacaa gagcaggtgg 1320
cagcagggga acgtcttctc atgctccgtg atgcatgagg ctctgcacaa ccactacacg 1380
cagaagagcc tctccctgtc tccgggtaaa 1410
<210> 229
<211> 213
<212> PRT
<213> 人工序列
<220>
<223> 合成多肽
<220>
<221> MISC_FEATURE
<223> 人源化抗体序列
<400> 229
Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Ser Ser Ile Ser Tyr Ile
20 25 30
His Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr
35 40 45
Ala Thr Ser Asn Leu Ala Ser Gly Val Pro Ser Arg Phe Ser Gly Ser
50 55 60
Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu
65 70 75 80
Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Trp Ser Ser Asp Pro Leu Thr
85 90 95
Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro
100 105 110
Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr
115 120 125
Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys
130 135 140
Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu
145 150 155 160
Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser
165 170 175
Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala
180 185 190
Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe
195 200 205
Asn Arg Gly Glu Cys
210
<210> 230
<211> 639
<212> DNA
<213> 人工序列
<220>
<223> 合成多核苷酸
<220>
<221> misc_feature
<223> 人源化抗体序列
<400> 230
gacatccagt tgacccagtc tccatccttc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgca gggccagctc aagtataagt tacatacact ggtatcagca aaaaccaggg 120
aaagccccta agctcctgat ctatgccaca tccaacctgg cttctggggt cccatcaagg 180
ttcagcggca gtggatctgg gacagaattc actctcacaa tcagcagcct gcagcctgaa 240
gattttgcaa cttattactg tcagcagtgg agtagtgacc cactcacgtt cggcggaggg 300
accaaggtgg agatcaaacg tacggtggct gcaccatctg tcttcatctt cccgccatct 360
gatgagcagt tgaaatctgg aactgcctct gttgtgtgcc tgctgaataa cttctatccc 420
agagaggcca aagtacagtg gaaggtggat aacgccctcc aatcgggtaa ctcccaggag 480
agtgtcacag agcaggacag caaggacagc acctacagcc tcagcagcac cctgacgctg 540
agcaaagcag actacgagaa acacaaagtc tacgcctgcg aagtcaccca tcagggcctg 600
agctcgcccg tcacaaagag cttcaacagg ggagagtgt 639
<210> 231
<211> 235
<212> PRT
<213> 人工序列
<220>
<223> 合成多肽
<220>
<221> MISC_FEATURE
<223> 人源化抗体序列
<400> 231
Met Asp Met Arg Val Pro Ala Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Arg Cys Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe
20 25 30
Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser
35 40 45
Ser Ser Ile Ser Tyr Ile His Trp Tyr Gln Gln Lys Pro Gly Lys Ala
50 55 60
Pro Lys Leu Leu Ile Tyr Ala Thr Ser Asn Leu Ala Ser Gly Val Pro
65 70 75 80
Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile
85 90 95
Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Trp
100 105 110
Ser Ser Asp Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
115 120 125
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
130 135 140
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
145 150 155 160
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
165 170 175
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
180 185 190
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
195 200 205
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
210 215 220
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
225 230 235
<210> 232
<211> 705
<212> DNA
<213> 人工序列
<220>
<223> 合成多核苷酸
<220>
<221> misc_feature
<223> 人源化抗体序列
<400> 232
atggacatga gggtccccgc tcagctcctg gggctcctgc tgctctggct cccaggtgcc 60
agatgtgaca tccagttgac ccagtctcca tccttcctgt ctgcatctgt aggagacaga 120
gtcaccatca cttgcagggc cagctcaagt ataagttaca tacactggta tcagcaaaaa 180
ccagggaaag cccctaagct cctgatctat gccacatcca acctggcttc tggggtccca 240
tcaaggttca gcggcagtgg atctgggaca gaattcactc tcacaatcag cagcctgcag 300
cctgaagatt ttgcaactta ttactgtcag cagtggagta gtgacccact cacgttcggc 360
ggagggacca aggtggagat caaacgtacg gtggctgcac catctgtctt catcttcccg 420
ccatctgatg agcagttgaa atctggaact gcctctgttg tgtgcctgct gaataacttc 480
tatcccagag aggccaaagt acagtggaag gtggataacg ccctccaatc gggtaactcc 540
caggagagtg tcacagagca ggacagcaag gacagcacct acagcctcag cagcaccctg 600
acgctgagca aagcagacta cgagaaacac aaagtctacg cctgcgaagt cacccatcag 660
ggcctgagct cgcccgtcac aaagagcttc aacaggggag agtgt 705
<210> 233
<211> 447
<212> PRT
<213> 人工序列
<220>
<223> 合成多肽
<220>
<221> MISC_FEATURE
<223> 人源化抗体序列
<400> 233
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Phe Asp Ile Lys Asp Tyr
20 25 30
Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Arg Val Asp Pro Asp Asn Gly Glu Thr Glu Phe Ala Pro Lys Phe
50 55 60
Pro Gly Lys Val Thr Met Thr Thr Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Asp Tyr Asp Gly Thr Tyr Thr Trp Phe Pro Tyr Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser
115 120 125
Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala
130 135 140
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val
145 150 155 160
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala
165 170 175
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val
180 185 190
Pro Ser Ser Asn Phe Gly Thr Gln Thr Tyr Thr Cys Asn Val Asp His
195 200 205
Lys Pro Ser Asn Thr Lys Val Asp Lys Thr Val Glu Arg Lys Cys Cys
210 215 220
Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val
225 230 235 240
Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr
245 250 255
Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu
260 265 270
Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys
275 280 285
Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Val Val Ser
290 295 300
Val Leu Thr Val Val His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys
305 310 315 320
Cys Lys Val Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu Lys Thr Ile
325 330 335
Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro
340 345 350
Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu
355 360 365
Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn
370 375 380
Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Met Leu Asp Ser
385 390 395 400
Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg
405 410 415
Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu
420 425 430
His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440 445
<210> 234
<211> 1341
<212> DNA
<213> 人工序列
<220>
<223> 合成多核苷酸
<220>
<221> misc_feature
<223> 人源化抗体序列
<400> 234
gaggtgcagc tggtgcagtc tggggctgag gtgaagaagc ctggggcctc agtgaaggtc 60
tcctgcaagg cttctggatt cgacattaag gactactata tacactgggt gcgacaggcc 120
cctggacaag ggcttgagtg gatcggaagg gttgatcctg acaatggtga gactgaattt 180
gccccgaagt tcccgggcaa ggtcaccatg accacagaca cgtccatcag cacagcctac 240
atggagctga gcaggctgag atctgacgac acggccgtgt attactgtgc gagagaagac 300
tacgatggta cctacacctg gtttccttat tggggccaag ggactctggt caccgtctct 360
agtgcctcca ccaagggccc atcggtcttc cccctggcgc cctgctccag gagcacctcc 420
gagagcacag cggccctggg ctgcctggtc aaggactact tccccgaacc ggtgacggtg 480
tcgtggaact caggcgctct gaccagcggc gtgcacacct tcccagctgt cctacagtcc 540
tcaggactct actccctcag cagcgtggtg accgtgccct ccagcaactt cggcacccag 600
acctacacct gcaacgtaga tcacaagccc agcaacacca aggtggacaa gacagttgag 660
cgcaaatgtt gtgtcgagtg cccaccgtgc ccagcaccac ctgtggcagg accgtcagtc 720
ttcctcttcc ccccaaaacc caaggacacc ctcatgatct cccggacccc tgaggtcacg 780
tgcgtggtgg tggacgtgag ccacgaagac cccgaggtcc agttcaactg gtacgtggac 840
ggcgtggagg tgcataatgc caagacaaag ccacgggagg agcagttcaa cagcacgttc 900
cgtgtggtca gcgtcctcac cgttgtgcac caggactggc tgaacggcaa ggagtacaag 960
tgcaaggtct ccaacaaagg cctcccagcc cccatcgaga aaaccatctc caaaaccaaa 1020
gggcagcccc gagaaccaca ggtgtacacc ctgcccccat cccgggagga gatgaccaag 1080
aaccaggtca gcctgacctg cctggtcaaa ggcttctacc ccagcgacat cgccgtggag 1140
tgggagagca atgggcagcc ggagaacaac tacaagacca cacctcccat gctggactcc 1200
gacggctcct tcttcctcta cagcaagctc accgtggaca agagcaggtg gcagcagggg 1260
aacgtcttct catgctccgt gatgcatgag gctctgcaca accactacac gcagaagagc 1320
ctctccctgt ctccgggtaa a 1341
<210> 235
<211> 466
<212> PRT
<213> 人工序列
<220>
<223> 合成多肽
<220>
<221> MISC_FEATURE
<223> 人源化抗体序列
<400> 235
Met Asp Trp Thr Trp Arg Ile Leu Phe Leu Val Ala Ala Ala Thr Gly
1 5 10 15
Ala His Ser Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys
20 25 30
Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Phe Asp Ile
35 40 45
Lys Asp Tyr Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu
50 55 60
Glu Trp Ile Gly Arg Val Asp Pro Asp Asn Gly Glu Thr Glu Phe Ala
65 70 75 80
Pro Lys Phe Pro Gly Lys Val Thr Met Thr Thr Asp Thr Ser Ile Ser
85 90 95
Thr Ala Tyr Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Glu Asp Tyr Asp Gly Thr Tyr Thr Trp Phe Pro
115 120 125
Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys
130 135 140
Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu
145 150 155 160
Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro
165 170 175
Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr
180 185 190
Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val
195 200 205
Val Thr Val Pro Ser Ser Asn Phe Gly Thr Gln Thr Tyr Thr Cys Asn
210 215 220
Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Thr Val Glu Arg
225 230 235 240
Lys Cys Cys Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly
245 250 255
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
260 265 270
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
275 280 285
Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
290 295 300
Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg
305 310 315 320
Val Val Ser Val Leu Thr Val Val His Gln Asp Trp Leu Asn Gly Lys
325 330 335
Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu
340 345 350
Lys Thr Ile Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
355 360 365
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
370 375 380
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
385 390 395 400
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Met
405 410 415
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
420 425 430
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
435 440 445
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
450 455 460
Gly Lys
465
<210> 236
<211> 1398
<212> DNA
<213> 人工序列
<220>
<223> 合成多核苷酸
<220>
<221> misc_feature
<223> 人源化抗体序列
<400> 236
atggactgga cctggaggat cctcttcttg gtggcagcag ccacaggagc ccactccgag 60
gtgcagctgg tgcagtctgg ggctgaggtg aagaagcctg gggcctcagt gaaggtctcc 120
tgcaaggctt ctggattcga cattaaggac tactatatac actgggtgcg acaggcccct 180
ggacaagggc ttgagtggat cggaagggtt gatcctgaca atggtgagac tgaatttgcc 240
ccgaagttcc cgggcaaggt caccatgacc acagacacgt ccatcagcac agcctacatg 300
gagctgagca ggctgagatc tgacgacacg gccgtgtatt actgtgcgag agaagactac 360
gatggtacct acacctggtt tccttattgg ggccaaggga ctctggtcac cgtctctagt 420
gcctccacca agggcccatc ggtcttcccc ctggcgccct gctccaggag cacctccgag 480
agcacagcgg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg 540
tggaactcag gcgctctgac cagcggcgtg cacaccttcc cagctgtcct acagtcctca 600
ggactctact ccctcagcag cgtggtgacc gtgccctcca gcaacttcgg cacccagacc 660
tacacctgca acgtagatca caagcccagc aacaccaagg tggacaagac agttgagcgc 720
aaatgttgtg tcgagtgccc accgtgccca gcaccacctg tggcaggacc gtcagtcttc 780
ctcttccccc caaaacccaa ggacaccctc atgatctccc ggacccctga ggtcacgtgc 840
gtggtggtgg acgtgagcca cgaagacccc gaggtccagt tcaactggta cgtggacggc 900
gtggaggtgc ataatgccaa gacaaagcca cgggaggagc agttcaacag cacgttccgt 960
gtggtcagcg tcctcaccgt tgtgcaccag gactggctga acggcaagga gtacaagtgc 1020
aaggtctcca acaaaggcct cccagccccc atcgagaaaa ccatctccaa aaccaaaggg 1080
cagccccgag aaccacaggt gtacaccctg cccccatccc gggaggagat gaccaagaac 1140
caggtcagcc tgacctgcct ggtcaaaggc ttctacccca gcgacatcgc cgtggagtgg 1200
gagagcaatg ggcagccgga gaacaactac aagaccacac ctcccatgct ggactccgac 1260
ggctccttct tcctctacag caagctcacc gtggacaaga gcaggtggca gcaggggaac 1320
gtcttctcat gctccgtgat gcatgaggct ctgcacaacc actacacgca gaagagcctc 1380
tccctgtctc cgggtaaa 1398
<210> 237
<211> 7
<212> PRT
<213> 家鼷鼠
<400> 237
Gly Thr Ser Asn Leu Ala Ser
1 5
<210> 238
<211> 8
<212> PRT
<213> 家鼷鼠
<400> 238
Gln Gln Trp Thr Thr Thr Tyr Thr
1 5
<210> 239
<211> 11
<212> PRT
<213> 家鼷鼠
<400> 239
Arg Ala Ser Gln Asp Ile Ser Ser Tyr Leu Asn
1 5 10
<210> 240
<211> 7
<212> PRT
<213> 家鼷鼠
<400> 240
Ser Thr Ser Arg Leu Asn Ser
1 5
<210> 241
<211> 8
<212> PRT
<213> 家鼷鼠
<400> 241
Gln Gln Asp Ile Lys His Pro Thr
1 5
<210> 242
<211> 11
<212> PRT
<213> 家鼷鼠
<400> 242
Lys Ala Ser Gln Asp Val Phe Thr Ala Val Ala
1 5 10
<210> 243
<211> 7
<212> PRT
<213> 家鼷鼠
<400> 243
Trp Ala Ser Thr Arg His Thr
1 5
<210> 244
<211> 9
<212> PRT
<213> 家鼷鼠
<400> 244
Gln Gln Tyr Ser Ser Tyr Pro Leu Thr
1 5
<210> 245
<211> 5
<212> PRT
<213> 家鼷鼠
<400> 245
Asp Tyr Asn Met His
1 5
<210> 246
<211> 17
<212> PRT
<213> 家鼷鼠
<400> 246
Glu Ile Asn Pro Asn Ser Gly Gly Ala Gly Tyr Asn Gln Lys Phe Lys
1 5 10 15
Gly
<210> 247
<211> 14
<212> PRT
<213> 家鼷鼠
<400> 247
Leu Gly Tyr Asp Asp Ile Tyr Asp Asp Trp Tyr Phe Asp Val
1 5 10
<210> 248
<211> 5
<212> PRT
<213> 家鼷鼠
<400> 248
Asp Tyr Asn Met His
1 5
<210> 249
<211> 17
<212> PRT
<213> 家鼷鼠
<400> 249
Glu Ile Asn Pro Asn Ser Gly Gly Ser Gly Tyr Asn Gln Lys Phe Lys
1 5 10 15
Gly
<210> 250
<211> 14
<212> PRT
<213> 家鼷鼠
<400> 250
Leu Val Tyr Asp Gly Ser Tyr Glu Asp Trp Tyr Phe Asp Val
1 5 10
<210> 251
<211> 5
<212> PRT
<213> 家鼷鼠
<400> 251
Asp Tyr Asn Met His
1 5
<210> 252
<211> 17
<212> PRT
<213> 家鼷鼠
<400> 252
Glu Ile Asn Pro Asn Ser Gly Gly Ala Gly Tyr Asn Gln Gln Phe Lys
1 5 10 15
Gly
<210> 253
<211> 14
<212> PRT
<213> 家鼷鼠
<400> 253
Leu Gly Tyr Val Gly Asn Tyr Glu Asp Trp Tyr Phe Asp Val
1 5 10
<210> 254
<211> 5
<212> PRT
<213> 家鼷鼠
<400> 254
Asp Tyr Asn Met His
1 5
<210> 255
<211> 17
<212> PRT
<213> 家鼷鼠
<400> 255
Glu Ile Asn Pro Asn Ser Gly Gly Ala Gly Tyr Asn Gln Lys Phe Lys
1 5 10 15
Gly
<210> 256
<211> 14
<212> PRT
<213> 家鼷鼠
<400> 256
Leu Gly Tyr Asp Asp Ile Tyr Asp Asp Trp Tyr Phe Asp Val
1 5 10
<210> 257
<211> 5
<212> PRT
<213> 家鼷鼠
<400> 257
Asp Tyr Asn Met His
1 5
<210> 258
<211> 17
<212> PRT
<213> 家鼷鼠
<400> 258
Glu Ile Asn Pro Asn Ser Gly Gly Ala Gly Tyr Asn Gln Lys Phe Lys
1 5 10 15
Gly
<210> 259
<211> 14
<212> PRT
<213> 家鼷鼠
<400> 259
Leu Gly Tyr Asp Asp Ile Tyr Asp Asp Trp Tyr Phe Asp Val
1 5 10
<210> 260
<211> 5
<212> PRT
<213> 家鼷鼠
<400> 260
Asp Tyr Asn Met His
1 5
<210> 261
<211> 17
<212> PRT
<213> 家鼷鼠
<400> 261
Glu Ile Asn Pro Asn Ser Gly Gly Ala Gly Tyr Asn Gln Lys Phe Lys
1 5 10 15
Gly
<210> 262
<211> 14
<212> PRT
<213> 家鼷鼠
<400> 262
Leu Gly Tyr Asp Asp Ile Tyr Asp Asp Trp Tyr Phe Asp Val
1 5 10
<210> 263
<211> 5
<212> PRT
<213> 家鼷鼠
<400> 263
Asp Tyr Asn Met His
1 5
<210> 264
<211> 17
<212> PRT
<213> 家鼷鼠
<400> 264
Glu Ile Asn Pro Asn Ser Gly Gly Ser Gly Tyr Asn Gln Lys Phe Lys
1 5 10 15
Gly
<210> 265
<211> 14
<212> PRT
<213> 家鼷鼠
<400> 265
Leu Gly Tyr Tyr Gly Asn Tyr Glu Asp Trp Tyr Phe Asp Val
1 5 10
<210> 266
<211> 5
<212> PRT
<213> 家鼷鼠
<400> 266
Asp Tyr Tyr Ile His
1 5
<210> 267
<211> 17
<212> PRT
<213> 家鼷鼠
<400> 267
Arg Ile Asp Pro Asp Asn Gly Glu Ser Thr Tyr Val Pro Lys Phe Gln
1 5 10 15
Gly
<210> 268
<211> 13
<212> PRT
<213> 家鼷鼠
<400> 268
Glu Gly Leu Asp Tyr Gly Asp Tyr Tyr Ala Val Asp Tyr
1 5 10
<210> 269
<211> 5
<212> PRT
<213> 家鼷鼠
<400> 269
Asp Tyr Ile Met His
1 5
<210> 270
<211> 17
<212> PRT
<213> 家鼷鼠
<400> 270
Tyr Ile Asn Pro Tyr Asn Asp Asp Thr Glu Tyr Asn Glu Lys Phe Lys
1 5 10 15
Gly
<210> 271
<211> 11
<212> PRT
<213> 家鼷鼠
<400> 271
Ser Ile Tyr Tyr Tyr Asp Ala Pro Phe Ala Tyr
1 5 10
<210> 272
<211> 5
<212> PRT
<213> 家鼷鼠
<400> 272
Asp Tyr Tyr Met His
1 5
<210> 273
<211> 17
<212> PRT
<213> 家鼷鼠
<400> 273
Arg Ile Asp Pro Glu Asn Gly Asp Ile Ile Tyr Asp Pro Lys Phe Gln
1 5 10 15
Gly
<210> 274
<211> 10
<212> PRT
<213> 家鼷鼠
<400> 274
Asp Ala Gly Asp Pro Ala Trp Phe Thr Tyr
1 5 10
<210> 275
<211> 10
<212> PRT
<213> 家鼷鼠
<400> 275
Arg Ala Ser Ser Ser Val Tyr Tyr Met His
1 5 10
<210> 276
<211> 7
<212> PRT
<213> 家鼷鼠
<400> 276
Ala Thr Ser Asn Leu Ala Ser
1 5
<210> 277
<211> 9
<212> PRT
<213> 家鼷鼠
<400> 277
Gln Gln Trp Ser Ser Asp Pro Leu Thr
1 5
<210> 278
<211> 12
<212> PRT
<213> 家鼷鼠
<400> 278
Ser Val Ser Ser Thr Ile Ser Ser Asn His Leu His
1 5 10
<210> 279
<211> 7
<212> PRT
<213> 家鼷鼠
<400> 279
Gly Thr Ser Asn Leu Ala Ser
1 5
<210> 280
<211> 9
<212> PRT
<213> 家鼷鼠
<400> 280
Gln Gln Trp Ser Ser Tyr Pro Leu Thr
1 5
<210> 281
<211> 10
<212> PRT
<213> 家鼷鼠
<400> 281
Arg Ala Ser Ser Ser Ile Ser Tyr Ile His
1 5 10
<210> 282
<211> 7
<212> PRT
<213> 家鼷鼠
<400> 282
Ala Thr Ser Asn Leu Ala Ser
1 5
<210> 283
<211> 9
<212> PRT
<213> 家鼷鼠
<400> 283
Gln Gln Trp Ser Ser Asp Pro Leu Thr
1 5
<210> 284
<211> 12
<212> PRT
<213> 家鼷鼠
<400> 284
Arg Ala Ser Ser Ser Val Thr Ser Ser Tyr Leu Asn
1 5 10
<210> 285
<211> 7
<212> PRT
<213> 家鼷鼠
<400> 285
Ser Thr Ser Asn Leu Ala Ser
1 5
<210> 286
<211> 9
<212> PRT
<213> 家鼷鼠
<400> 286
Gln Gln Tyr Asp Phe Phe Pro Ser Thr
1 5
<210> 287
<211> 5
<212> PRT
<213> 家鼷鼠
<400> 287
Asp Tyr Phe Ile His
1 5
<210> 288
<211> 17
<212> PRT
<213> 家鼷鼠
<400> 288
Arg Leu Asp Pro Glu Asp Gly Glu Ser Asp Tyr Ala Pro Lys Phe Gln
1 5 10 15
Asp
<210> 289
<211> 12
<212> PRT
<213> 家鼷鼠
<400> 289
Glu Asp Tyr Asp Gly Thr Tyr Thr Phe Phe Pro Tyr
1 5 10
<210> 290
<211> 5
<212> PRT
<213> 家鼷鼠
<400> 290
Asp Phe Tyr Leu His
1 5
<210> 291
<211> 17
<212> PRT
<213> 家鼷鼠
<400> 291
Arg Ile Asp Pro Glu Asn Gly Asp Thr Leu Tyr Asp Pro Lys Phe Gln
1 5 10 15
Asp
<210> 292
<211> 16
<212> PRT
<213> 家鼷鼠
<400> 292
Glu Ala Asp Tyr Phe His Asp Gly Thr Ser Tyr Trp Tyr Phe Asp Val
1 5 10 15
<210> 293
<211> 5
<212> PRT
<213> 家鼷鼠
<400> 293
Asp Tyr Tyr Ile His
1 5
<210> 294
<211> 17
<212> PRT
<213> 家鼷鼠
<400> 294
Arg Val Asp Pro Asp Asn Gly Glu Thr Glu Phe Ala Pro Lys Phe Pro
1 5 10 15
Gly
<210> 295
<211> 12
<212> PRT
<213> 家鼷鼠
<400> 295
Glu Asp Tyr Asp Gly Thr Tyr Thr Trp Phe Pro Tyr
1 5 10
<210> 296
<211> 5
<212> PRT
<213> 家鼷鼠
<400> 296
Asp Tyr Tyr Met Asn
1 5
<210> 297
<211> 17
<212> PRT
<213> 家鼷鼠
<400> 297
Asp Ile Asn Pro Tyr Asn Asp Asp Thr Thr Tyr Asn His Lys Phe Lys
1 5 10 15
Gly
<210> 298
<211> 11
<212> PRT
<213> 家鼷鼠
<400> 298
Glu Thr Ala Val Ile Thr Thr Asn Ala Met Asp
1 5 10
<210> 299
<211> 130
<212> PRT
<213> 家鼷鼠
<400> 299
Met Asp Phe Gln Val Gln Ile Phe Ser Phe Met Leu Ile Ser Val Thr
1 5 10 15
Val Ile Leu Ser Ser Gly Glu Ile Val Leu Thr Gln Ser Pro Ala Leu
20 25 30
Met Ala Ala Ser Pro Gly Glu Lys Val Thr Ile Thr Cys Ser Val Ser
35 40 45
Ser Ser Ile Ser Ser Ser Asn Leu His Trp Ser Gln Gln Lys Ser Gly
50 55 60
Thr Ser Pro Lys Leu Trp Ile Tyr Gly Thr Ser Asn Leu Ala Ser Gly
65 70 75 80
Val Pro Val Arg Phe Ser Gly Ser Gly Ser Gly Thr Ser Tyr Ser Leu
85 90 95
Thr Ile Ser Ser Met Glu Ala Glu Asp Ala Ala Thr Tyr Tyr Cys Gln
100 105 110
Gln Trp Thr Thr Thr Tyr Thr Phe Gly Ser Gly Thr Lys Leu Glu Leu
115 120 125
Lys Arg
130
<210> 300
<211> 390
<212> DNA
<213> 家鼷鼠
<400> 300
atggattttc aggtgcagat tttcagcttc atgctaatca gtgtcacagt catattgtcc 60
agtggagaaa ttgtgctcac ccagtctcca gcactcatgg ctgcatctcc aggggagaag 120
gtcaccatca cctgcagtgt cagctcgagt ataagttcca gcaacttaca ctggtcccag 180
cagaagtcag gaacctcccc caaactctgg atttatggca catccaacct tgcttctgga 240
gtccctgttc gcttcagtgg cagtggatct gggacctctt attctctcac aatcagcagc 300
atggaggctg aagatgctgc cacttattac tgtcaacagt ggactactac gtatacgttc 360
ggatcgggga ccaagctgga gctgaaacgt 390
<210> 301
<211> 141
<212> PRT
<213> 家鼷鼠
<400> 301
Met Gly Trp Asn Trp Ile Ile Phe Phe Leu Met Ala Val Val Thr Gly
1 5 10 15
Val Asn Ser Glu Val Gln Leu Arg Gln Ser Gly Ala Asp Leu Val Lys
20 25 30
Pro Gly Ala Ser Val Lys Leu Ser Cys Thr Ala Ser Gly Phe Asn Ile
35 40 45
Lys Asp Tyr Tyr Ile His Trp Val Lys Gln Arg Pro Glu Gln Gly Leu
50 55 60
Glu Trp Ile Gly Arg Ile Asp Pro Asp Asn Gly Glu Ser Thr Tyr Val
65 70 75 80
Pro Lys Phe Gln Gly Lys Ala Thr Ile Thr Ala Asp Thr Ser Ser Asn
85 90 95
Thr Ala Tyr Leu Gln Leu Arg Ser Leu Thr Ser Glu Asp Thr Ala Ile
100 105 110
Tyr Tyr Cys Gly Arg Glu Gly Leu Asp Tyr Gly Asp Tyr Tyr Ala Val
115 120 125
Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr Val Ser Ser
130 135 140
<210> 302
<211> 423
<212> DNA
<213> 家鼷鼠
<400> 302
atgggatgga actggatcat cttcttcctg atggcagtgg ttacaggggt caattcagag 60
gtgcagttgc ggcagtctgg ggcagacctt gtgaagccag gggcctcagt caagttgtcc 120
tgcacagctt ctggcttcaa cattaaagac tactatatac actgggtgaa gcagaggcct 180
gaacagggcc tggagtggat tggaaggatt gatcctgata atggtgaaag tacatatgtc 240
ccgaagttcc agggcaaggc cactataaca gcagacacat catccaacac agcctaccta 300
caactcagaa gcctgacatc tgaggacact gccatctatt attgtgggag agaggggctc 360
gactatggtg actactatgc tgtggactac tggggtcaag gaacctcggt cacagtctcg 420
agc 423
<210> 303
<211> 130
<212> PRT
<213> 人工序列
<220>
<223> 合成多肽
<220>
<221> MISC_FEATURE
<223> 人源化抗体序列
<400> 303
Met Asp Met Arg Val Pro Ala Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Arg Cys Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe
20 25 30
Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Ser Val Ser
35 40 45
Ser Ser Ile Ser Ser Ser Asn Leu His Trp Tyr Gln Gln Lys Pro Gly
50 55 60
Lys Ala Pro Lys Leu Leu Ile Tyr Gly Thr Ser Asn Leu Ala Ser Gly
65 70 75 80
Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu
85 90 95
Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln
100 105 110
Gln Trp Thr Thr Thr Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile
115 120 125
Lys Arg
130
<210> 304
<211> 390
<212> DNA
<213> 人工序列
<220>
<223> 合成多核苷酸
<220>
<221> misc_feature
<223> 人源化抗体序列
<400> 304
atggatatgc gcgtgccggc gcagctgctg ggcctgctgc tgctgtggct gccgggcgcg 60
cgctgcgata ttcagctgac ccagagcccg agctttctga gcgcgagcgt gggcgatcgc 120
gtgaccatta cctgcagcgt gagcagcagc attagcagca gcaacctgca ttggtatcag 180
cagaaaccgg gcaaagcgcc gaaactgctg atttatggca ccagcaacct ggcgagcggc 240
gtgccgagcc gctttagcgg cagcggcagc ggcaccgaat ttaccctgac cattagcagc 300
ctgcagccgg aagattttgc gacctattat tgccagcagt ggaccaccac ctataccttt 360
ggccagggca ccaaactgga aattaaacgt 390
<210> 305
<211> 141
<212> PRT
<213> 人工序列
<220>
<223> 合成多肽
<220>
<221> MISC_FEATURE
<223> 人源化抗体序列
<400> 305
Met Asp Trp Thr Trp Ser Ile Leu Phe Leu Val Ala Ala Pro Thr Gly
1 5 10 15
Ala His Ser Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys
20 25 30
Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Phe Asn Ile
35 40 45
Lys Asp Tyr Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu
50 55 60
Glu Trp Met Gly Arg Ile Asp Pro Asp Asn Gly Glu Ser Thr Tyr Val
65 70 75 80
Pro Lys Phe Gln Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser
85 90 95
Thr Ala Tyr Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Glu Gly Leu Asp Tyr Gly Asp Tyr Tyr Ala Val
115 120 125
Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135 140
<210> 306
<211> 423
<212> DNA
<213> 人工序列
<220>
<223> 合成多核苷酸
<220>
<221> misc_feature
<223> 人源化抗体序列
<400> 306
atggattgga cctggagcat tctgtttctg gtggcggcgc cgaccggcgc gcatagcgaa 60
gtgcagctgg tgcagagcgg cgcggaagtg aaaaaaccgg gcgcgagcgt gaaagtgagc 120
tgcaaagcga gcggctttaa cattaaagat tattatattc attgggtgcg ccaggcgccg 180
ggccagggcc tggaatggat gggccgcatt gatccggata acggcgaaag cacctatgtg 240
ccgaaatttc agggccgcgt gaccatgacc accgatacca gcaccagcac cgcgtatatg 300
gaactgcgca gcctgcgcag cgatgatacc gcggtgtatt attgcgcgcg cgaaggcctg 360
gattatggcg attattatgc ggtggattat tggggccagg gcaccctggt gaccgtctcg 420
agc 423
<210> 307
<211> 127
<212> PRT
<213> 人工序列
<220>
<223> 合成多肽
<220>
<221> MISC_FEATURE
<223> 人源化抗体序列
<400> 307
Met Met Ser Ser Ala Gln Phe Leu Gly Leu Leu Leu Leu Cys Phe Gln
1 5 10 15
Gly Thr Arg Cys Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser
20 25 30
Ala Ser Leu Gly Asp Arg Val Asn Ile Ser Cys Arg Ala Ser Gln Asp
35 40 45
Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Val
50 55 60
Lys Leu Leu Ile Tyr Ser Thr Ser Arg Leu Asn Ser Gly Val Pro Ser
65 70 75 80
Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Ser
85 90 95
Asn Leu Ala Gln Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Asp Ile
100 105 110
Lys His Pro Thr Phe Gly Gly Gly Thr Lys Leu Glu Leu Lys Arg
115 120 125
<210> 308
<211> 381
<212> DNA
<213> 家鼷鼠
<400> 308
atgatgtcct ctgctcagtt ccttggtctc ctgttgctct gttttcaagg taccagatgt 60
gatatccaga tgacacagac tacatcctcc ctgtctgcct ctctgggaga cagagtcaac 120
atcagctgca gggcaagtca ggacattagc agttatttaa actggtatca gcagaaacca 180
gatggaactg ttaaactcct gatctactcc acatcaagat taaactcagg agtcccatca 240
aggttcagtg gcagtgggtc tgggacagat tattctctca ctattagcaa cctggcacaa 300
gaagatattg ccacttactt ttgccaacag gatattaagc atccgacgtt cggtggaggc 360
accaagttgg agctgaaacg t 381
<210> 309
<211> 139
<212> PRT
<213> 家鼷鼠
<400> 309
Met Glu Trp Ile Trp Ile Phe Leu Phe Leu Leu Ser Gly Thr Ala Gly
1 5 10 15
Val His Ser Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys
20 25 30
Pro Gly Ala Ser Val Lys Met Ser Cys Lys Ala Ser Gly Phe Thr Phe
35 40 45
Thr Asp Tyr Ile Met His Trp Val Lys Gln Lys Pro Gly Gln Gly Leu
50 55 60
Glu Trp Ile Gly Tyr Ile Asn Pro Tyr Asn Asp Asp Thr Glu Tyr Asn
65 70 75 80
Glu Lys Phe Lys Gly Lys Ala Thr Leu Thr Ser Asp Lys Ser Ser Ser
85 90 95
Thr Ala Tyr Met Asp Leu Ser Ser Leu Thr Ser Glu Gly Ser Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Ser Ile Tyr Tyr Tyr Asp Ala Pro Phe Ala Tyr
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 310
<211> 417
<212> DNA
<213> 家鼷鼠
<400> 310
atggaatgga tctggatatt tctcttcctc ctgtcaggaa ctgcaggtgt ccactctgag 60
gtccagctgc agcagtctgg acctgagctg gtaaagcctg gggcttcagt gaagatgtcc 120
tgcaaggctt ctgggttcac attcactgac tacattatgc actgggtgaa gcagaagcct 180
gggcagggcc ttgagtggat tggatatatt aatccttaca atgatgatac tgaatacaat 240
gagaagttca aaggcaaggc cacactgact tcagacaaat cctccagcac agcctacatg 300
gatctcagca gtctgacctc tgagggctct gcggtctatt actgtgcaag atcgatttat 360
tactacgatg ccccgtttgc ttactggggc caagggactc tggtcacagt ctcgagc 417
<210> 311
<211> 127
<212> PRT
<213> 人工序列
<220>
<223> 合成多肽
<220>
<221> MISC_FEATURE
<223> 人源化抗体序列
<400> 311
Met Met Ser Ser Ala Gln Phe Leu Gly Leu Leu Leu Leu Cys Phe Gln
1 5 10 15
Gly Thr Arg Cys Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser
20 25 30
Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp
35 40 45
Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro
50 55 60
Lys Leu Leu Ile Tyr Ser Thr Ser Arg Leu Asn Ser Gly Val Pro Ser
65 70 75 80
Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser
85 90 95
Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Asp Ile
100 105 110
Lys His Pro Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg
115 120 125
<210> 312
<211> 381
<212> DNA
<213> 人工序列
<220>
<223> 合成多核苷酸
<220>
<221> misc_feature
<223> 人源化抗体序列
<400> 312
atgatgtcct ctgctcagtt ccttggtctc ctgttgctct gttttcaagg taccagatgt 60
gatatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggtga ccgtgtcacc 120
atcacttgcc gcgcaagtca ggatattagc agctatttaa attggtatca gcagaaacca 180
gggaaagccc ctaagctcct gatctattct acttcccgtt tgaatagtgg ggtcccatca 240
cgcttcagtg gcagtggctc tgggacagat ttcactctca ccatcagcag tctgcaacct 300
gaagattttg caacttacta ctgtcaacag gatattaaac accctacgtt cggtcaaggc 360
accaaggtgg agatcaaacg t 381
<210> 313
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成多肽
<220>
<221> MISC_FEATURE
<223> 人源化抗体序列
<400> 313
Met Glu Trp Ile Trp Ile Phe Leu Phe Leu Leu Ser Gly Thr Ala Gly
1 5 10 15
Val His Ser Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys
20 25 30
Pro Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly Phe Thr Phe
35 40 45
Thr Asp Tyr Ile Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu
50 55 60
Glu Trp Met Gly Tyr Ile Asn Pro Tyr Asn Asp Asp Thr Glu Tyr Asn
65 70 75 80
Glu Lys Phe Lys Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser
85 90 95
Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Ser Ile Tyr Tyr Tyr Asp Ala Pro Phe Ala Tyr
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 314
<211> 107
<212> PRT
<213> 家鼷鼠
<400> 314
Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser Ala Ser Leu Gly
1 5 10 15
Asp Arg Val Asn Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Ser Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Val Lys Leu Leu Ile
35 40 45
Tyr Ser Thr Ser Arg Leu Asn Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Ser Asn Leu Ala Gln
65 70 75 80
Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Asp Ile Lys His Pro Thr
85 90 95
Phe Gly Gly Gly Thr Lys Leu Glu Leu Lys Arg
100 105
<210> 315
<211> 128
<212> PRT
<213> 家鼷鼠
<400> 315
Met Lys Ser Gln Thr Gln Val Phe Val Tyr Met Leu Leu Trp Leu Ser
1 5 10 15
Gly Val Glu Gly Asp Ile Val Met Thr Gln Ser His Lys Phe Met Ser
20 25 30
Thr Ser Val Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp
35 40 45
Val Phe Thr Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro
50 55 60
Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Asp
65 70 75 80
Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser
85 90 95
Asn Val Gln Ser Glu Asp Leu Ala Asp Tyr Phe Cys Gln Gln Tyr Ser
100 105 110
Ser Tyr Pro Leu Thr Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys Arg
115 120 125
<210> 316
<211> 381
<212> DNA
<213> 家鼷鼠
<400> 316
atgaagtcac agacccaggt ctttgtatac atgttgctgt ggttgtctgg tgttgaagga 60
gacattgtga tgacccagtc tcacaaattc atgtccacgt cagtaggaga cagggtcacc 120
atcacctgca aggccagtca ggatgtcttt actgctgtag cctggtatca acagaaacca 180
ggacaatctc ctaaactact gatttactgg gcatccaccc ggcacactgg agtccctgat 240
cgcttcacag gcagtggatc tgggacagat ttcactctca ccattagcaa tgtgcagtct 300
gaagacttgg cagattattt ctgtcaacaa tatagcagct atcctctcac gttcggtgct 360
gggaccaagt tggagctgaa a 381
<210> 317
<211> 138
<212> PRT
<213> 家鼷鼠
<400> 317
Met Gly Trp Asn Trp Ile Ile Phe Phe Leu Met Ala Val Val Thr Gly
1 5 10 15
Val Asn Ser Glu Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg
20 25 30
Pro Gly Ala Leu Val Lys Leu Ser Cys Lys Ala Ser Gly Phe Asn Ile
35 40 45
Lys Asp Tyr Tyr Met His Trp Val Lys Gln Arg Pro Glu Gln Gly Leu
50 55 60
Glu Trp Ile Gly Arg Ile Asp Pro Glu Asn Gly Asp Ile Ile Tyr Asp
65 70 75 80
Pro Lys Phe Gln Gly Lys Ala Ser Ile Thr Thr Asp Thr Ser Ser Asn
85 90 95
Thr Ala Tyr Leu Gln Leu Ser Ser Leu Thr Ser Glu Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Ala Tyr Asp Ala Gly Asp Pro Ala Trp Phe Thr Tyr Trp
115 120 125
Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 318
<211> 411
<212> DNA
<213> 家鼷鼠
<400> 318
atgggatgga actggatcat cttcttcctg atggcagtgg ttacaggggt caattcagag 60
gttcagctgc agcagtctgg ggctgagctt gtgaggccag gggccttagt caagttgtcc 120
tgcaaagctt ctggcttcaa tattaaagac tactatatgc actgggtgaa gcagaggcct 180
gaacagggcc tggagtggat tggaaggatt gatcctgaga atggtgatat tatatatgac 240
ccgaagttcc agggcaaggc cagtataaca acagacacat cctccaacac agcctacctg 300
cagctcagca gcctgacgtc tgaggacact gccgtctatt actgtgctta cgatgctggt 360
gaccccgcct ggtttactta ctggggccaa gggactctgg tcaccgtctc g 411
<210> 319
<211> 130
<212> PRT
<213> 家鼷鼠
<400> 319
Met Asp Met Arg Val Pro Ala Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Arg Gly Ala Arg Cys Asp Ile Gln Met Thr Gln Ser Pro Ser Ser
20 25 30
Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser
35 40 45
Gln Asp Val Phe Thr Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys
50 55 60
Ala Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg His Thr Gly Val
65 70 75 80
Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
85 90 95
Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln
100 105 110
Tyr Ser Ser Tyr Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile
115 120 125
Lys Arg
130
<210> 320
<211> 390
<212> DNA
<213> 家鼷鼠
<400> 320
atggatatgc gcgtgccggc gcagctgctg ggcctgctgc tgctgtggct gcgcggcgcg 60
cgctgcgata tccagatgac ccagagcccg agcagcctga gcgcgagcgt gggcgatcgc 120
gtgaccatta cctgcaaagc gagccaggat gtgtttaccg cggtggcgtg gtatcagcag 180
aaaccgggca aagcgccgaa actgctgatt tattgggcga gcacccgcca taccggcgtg 240
ccgagtcgct ttagcggcag cggcagcggc accgatttta ccctgaccat tagcagcctg 300
cagccggaag attttgcgac ctattattgc cagcagtata gcagctatcc gctgaccttt 360
ggcggcggca ccaaagtgga aattaaacgt 390
<210> 321
<211> 138
<212> PRT
<213> 人工序列
<220>
<223> 合成多肽
<220>
<221> MISC_FEATURE
<223> 人源化抗体序列
<400> 321
Met Asp Trp Thr Trp Ser Ile Leu Phe Leu Val Ala Ala Pro Thr Gly
1 5 10 15
Ala His Ser Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys
20 25 30
Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Phe Asn Ile
35 40 45
Lys Asp Tyr Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu
50 55 60
Glu Trp Ile Gly Arg Ile Asp Pro Glu Asn Gly Asp Ile Ile Tyr Asp
65 70 75 80
Pro Lys Phe Gln Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser
85 90 95
Thr Ala Tyr Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Ala Tyr Asp Ala Gly Asp Pro Ala Trp Phe Thr Tyr Trp
115 120 125
Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 322
<211> 414
<212> DNA
<213> 人工序列
<220>
<223> 合成多核苷酸
<220>
<221> misc_feature
<223> 人源化抗体序列
<400> 322
atggattgga cctggagcat tctgtttctg gtggcggcgc cgaccggcgc gcatagcgaa 60
gtgcagctgg tgcagagcgg cgcggaagtg aaaaaaccgg gcgcgagcgt gaaagtgagc 120
tgcaaagcga gcggctttaa cattaaagat tattatatgc attgggtgcg ccaggcgccg 180
ggccagggcc tggaatggat cggccgcatt gatccggaaa acggcgatat tatttatgat 240
ccgaaatttc agggccgcgt gaccatgacc accgatacca gcaccagcac cgcgtatatg 300
gaactgcgca gcctgcgcag cgatgatacc gcggtgtatt attgcgcgta tgatgcgggc 360
gatccggcgt ggtttaccta ttggggccag ggcaccctgg tgaccgtctc gagc 414
<210> 323
<211> 106
<212> PRT
<213> 家鼷鼠
<400> 323
Thr Asp Ala Ala Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln
1 5 10 15
Leu Thr Ser Gly Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr
20 25 30
Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln
35 40 45
Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr
50 55 60
Tyr Ser Met Ser Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg
65 70 75 80
His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro
85 90 95
Ile Val Lys Ser Phe Asn Arg Asn Glu Cys
100 105
<210> 324
<211> 320
<212> PRT
<213> 家鼷鼠
<400> 324
Ala Lys Thr Thr Pro Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala
1 5 10 15
Ala Gln Thr Asn Ser Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser
35 40 45
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu
50 55 60
Ser Ser Ser Val Thr Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val
65 70 75 80
Thr Cys Asn Val Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys
85 90 95
Ile Val Pro Arg Asp Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro
100 105 110
Glu Val Ser Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu
115 120 125
Thr Ile Thr Leu Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser
130 135 140
Lys Asp Asp Pro Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu
145 150 155 160
Val His Thr Ala Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr
165 170 175
Phe Arg Ser Val Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn
180 185 190
Gly Lys Glu Phe Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro
195 200 205
Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln
210 215 220
Val Tyr Thr Ile Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val
225 230 235 240
Ser Leu Thr Cys Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val
245 250 255
Glu Trp Gln Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln
260 265 270
Pro Ile Met Asp Thr Asp Gly Ser Tyr Phe Val Tyr Ser Lys Leu Asn
275 280 285
Val Gln Lys Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val
290 295 300
Leu His Glu Gly Leu His Asn His His Thr Glu Lys Ser Leu Ser His
305 310 315 320
<210> 325
<211> 106
<212> PRT
<213> 智人
<400> 325
Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln
1 5 10 15
Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr
20 25 30
Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser
35 40 45
Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr
50 55 60
Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys
65 70 75 80
His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro
85 90 95
Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
100 105
<210> 326
<211> 327
<212> PRT
<213> 智人
<400> 326
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg
1 5 10 15
Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr
65 70 75 80
Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys
85 90 95
Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro
100 105 110
Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
115 120 125
Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val
130 135 140
Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp
145 150 155 160
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe
165 170 175
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp
180 185 190
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu
195 200 205
Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg
210 215 220
Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys
225 230 235 240
Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp
245 250 255
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys
260 265 270
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser
275 280 285
Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser
290 295 300
Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser
305 310 315 320
Leu Ser Leu Ser Leu Gly Lys
325
<210> 327
<211> 120
<212> PRT
<213> 家鼷鼠
<400> 327
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Phe Thr Phe Thr Asp Tyr
20 25 30
Ile Met His Trp Val Lys Gln Lys Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Tyr Asn Asp Asp Thr Glu Tyr Asn Glu Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Ser Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Asp Leu Ser Ser Leu Thr Ser Glu Gly Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Ser Ile Tyr Tyr Tyr Asp Ala Pro Phe Ala Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 328
<211> 120
<212> PRT
<213> 家鼷鼠
<400> 328
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Phe Thr Phe Thr Asp Tyr
20 25 30
Ile Met His Trp Val Lys Gln Lys Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Tyr Asn Asp Asp Thr Glu Tyr Asn Glu Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Ser Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Asp Leu Ser Ser Leu Thr Ser Glu Gly Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Ser Ile Tyr Tyr Tyr Asp Ala Pro Phe Ala Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 329
<211> 120
<212> PRT
<213> 家鼷鼠
<400> 329
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Phe Thr Phe Thr Asp Tyr
20 25 30
Ile Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Tyr Ile Asn Pro Tyr Asn Asp Asp Thr Glu Tyr Asn Glu Lys Phe
50 55 60
Lys Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Ser Ile Tyr Tyr Tyr Asp Ala Pro Phe Ala Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 330
<211> 226
<212> PRT
<213> 家鼷鼠
<400> 330
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Phe Thr Phe Thr Asp Tyr
20 25 30
Ile Met His Trp Val Lys Gln Lys Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Tyr Asn Asp Asp Thr Glu Tyr Asn Glu Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Ser Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Asp Leu Ser Ser Leu Thr Ser Glu Gly Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Ser Ile Tyr Tyr Tyr Asp Ala Pro Phe Ala Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Thr Val Ala Ala Pro Ser Val Phe
115 120 125
Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val
130 135 140
Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp
145 150 155 160
Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr
165 170 175
Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr
180 185 190
Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val
195 200 205
Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly
210 215 220
Glu Cys
225
<210> 331
<211> 447
<212> PRT
<213> 家鼷鼠
<400> 331
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Phe Thr Phe Thr Asp Tyr
20 25 30
Ile Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Tyr Ile Asn Pro Tyr Asn Asp Asp Thr Glu Tyr Asn Glu Lys Phe
50 55 60
Lys Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Ser Ile Tyr Tyr Tyr Asp Ala Pro Phe Ala Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro
210 215 220
Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val
225 230 235 240
Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr
245 250 255
Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu
260 265 270
Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys
275 280 285
Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser
290 295 300
Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys
305 310 315 320
Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile
325 330 335
Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro
340 345 350
Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu
355 360 365
Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn
370 375 380
Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser
385 390 395 400
Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg
405 410 415
Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu
420 425 430
His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys
435 440 445
<210> 332
<211> 107
<212> PRT
<213> 家鼷鼠
<400> 332
Asp Ile Gln Met Thr Gln Ile Thr Ser Ser Leu Ser Ala Ser Leu Gly
1 5 10 15
Asp Arg Val Ser Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Asn Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Phe Lys Leu Leu Ile
35 40 45
Phe Tyr Thr Ser Arg Leu Leu Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Tyr Asn Leu Glu Gln
65 70 75 80
Glu Asp Phe Ala Thr Tyr Phe Cys Gln Gln Gly Asp Thr Leu Pro Tyr
85 90 95
Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 333
<211> 324
<212> PRT
<213> 家鼷鼠
<400> 333
Ala Lys Thr Thr Pro Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala
1 5 10 15
Ala Gln Thr Asn Ser Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser
35 40 45
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu
50 55 60
Ser Ser Ser Val Thr Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val
65 70 75 80
Thr Cys Asn Val Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys
85 90 95
Ile Val Pro Arg Asp Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro
100 105 110
Glu Val Ser Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu
115 120 125
Thr Ile Thr Leu Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser
130 135 140
Lys Asp Asp Pro Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu
145 150 155 160
Val His Thr Ala Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr
165 170 175
Phe Arg Ser Val Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn
180 185 190
Gly Lys Glu Phe Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro
195 200 205
Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln
210 215 220
Val Tyr Thr Ile Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val
225 230 235 240
Ser Leu Thr Cys Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val
245 250 255
Glu Trp Gln Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln
260 265 270
Pro Ile Met Asp Thr Asp Gly Ser Tyr Phe Ile Tyr Ser Lys Leu Asn
275 280 285
Val Gln Lys Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val
290 295 300
Leu His Glu Gly Leu His Asn His His Thr Glu Lys Ser Leu Ser His
305 310 315 320
Ser Pro Gly Lys
<210> 334
<211> 213
<212> PRT
<213> 家鼷鼠
<400> 334
Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser Ala Ser Leu Gly
1 5 10 15
Asp Arg Val Asn Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Ser Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Val Lys Leu Leu Ile
35 40 45
Tyr Ser Thr Ser Arg Leu Asn Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Ser Asn Leu Ala Gln
65 70 75 80
Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Asp Ile Lys His Pro Thr
85 90 95
Phe Gly Gly Gly Thr Lys Leu Glu Leu Lys Arg Thr Asp Ala Ala Pro
100 105 110
Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln Leu Thr Ser Gly Gly
115 120 125
Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr Pro Lys Asp Ile Asn
130 135 140
Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln Asn Gly Val Leu Asn
145 150 155 160
Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr Tyr Ser Met Ser Ser
165 170 175
Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg His Asn Ser Tyr Thr
180 185 190
Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro Ile Val Lys Ser Phe
195 200 205
Asn Arg Asn Glu Cys
210
<210> 335
<211> 444
<212> PRT
<213> 家鼷鼠
<400> 335
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Phe Thr Phe Thr Asp Tyr
20 25 30
Ile Met His Trp Val Lys Gln Lys Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Tyr Asn Asp Asp Thr Glu Tyr Asn Glu Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Ser Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Asp Leu Ser Ser Leu Thr Ser Glu Gly Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Ser Ile Tyr Tyr Tyr Asp Ala Pro Phe Ala Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Lys Thr Thr Pro Pro Ser Val
115 120 125
Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr Asn Ser Met Val Thr
130 135 140
Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val Thr Val Thr
145 150 155 160
Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr Val Pro Ser
180 185 190
Ser Thr Trp Pro Ser Glu Thr Val Thr Cys Asn Val Ala His Pro Ala
195 200 205
Ser Ser Thr Lys Val Asp Lys Lys Ile Val Pro Arg Asp Cys Gly Cys
210 215 220
Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser Ser Val Phe Ile Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro Lys Val
245 250 255
Thr Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu Val Gln Phe
260 265 270
Ser Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr Gln Pro
275 280 285
Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser Glu Leu Pro
290 295 300
Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg Val
305 310 315 320
Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr
325 330 335
Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro Lys
340 345 350
Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile Thr Asp
355 360 365
Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly Gln Pro
370 375 380
Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr Asp Gly Ser
385 390 395 400
Tyr Phe Val Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn Trp Glu Ala
405 410 415
Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His Asn His
420 425 430
His Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys
435 440
<210> 336
<211> 108
<212> PRT
<213> 家鼷鼠
<400> 336
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Phe Thr Ala
20 25 30
Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Ser Ser Tyr Pro Leu
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
100 105
<210> 337
<211> 324
<212> DNA
<213> 家鼷鼠
<400> 337
gatatccaga tgacccagag cccgagcagc ctgagcgcga gcgtgggcga tcgcgtgacc 60
attacctgca aagcgagcca ggatgtgttt accgcggtgg cgtggtatca gcagaaaccg 120
ggcaaagcgc cgaaactgct gatttattgg gcgagcaccc gccataccgg cgtgccgagt 180
cgctttagcg gcagcggcag cggcaccgat tttaccctga ccattagcag cctgcagccg 240
gaagattttg cgacctatta ttgccagcag tatagcagct atccgctgac ctttggcggc 300
ggcaccaaag tggaaattaa acgt 324
<210> 338
<211> 119
<212> PRT
<213> 家鼷鼠
<400> 338
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Phe Asn Ile Lys Asp Tyr
20 25 30
Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Arg Ile Asp Pro Glu Asn Gly Asp Ile Ile Tyr Asp Pro Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Tyr Asp Ala Gly Asp Pro Ala Trp Phe Thr Tyr Trp Gly Gln Gly
100 105 110
Thr Leu Val Thr Val Ser Ser
115
<210> 339
<211> 357
<212> DNA
<213> 家鼷鼠
<400> 339
gaagtgcagc tggtgcagag cggcgcggaa gtgaaaaaac cgggcgcgag cgtgaaagtg 60
agctgcaaag cgagcggctt taacattaaa gattattata tgcattgggt gcgccaggcg 120
ccgggccagg gcctggaatg gatcggccgc attgatccgg aaaacggcga tattatttat 180
gatccgaaat ttcagggccg cgtgaccatg accaccgata ccagcaccag caccgcgtat 240
atggaactgc gcagcctgcg cagcgatgat accgcggtgt attattgcgc gtatgatgcg 300
ggcgatccgg cgtggtttac ctattggggc cagggcaccc tggtgaccgt ctcgagc 357
<210> 340
<211> 1395
<212> DNA
<213> 家鼷鼠
<400> 340
atggactgga cctggaggat cctcttcttg gtggcagcag ccacaggagc ccactccgag 60
gtgcagctgg tgcagtctgg ggctgaggtg aagaagcctg ggtcctcggt gaaggtctcc 120
tgcaaggctt ctggttttac cttcaccgac tatattatgc actgggtgcg tcaggcccct 180
ggtcaagggc ttgagtggat gggctatatc aacccttata atgatgacac cgaatacaac 240
gagaagttca agggccgtgt cacgattacc gcggacaaat ccacgagcac agcctacatg 300
gagctgagca gcctgcgctc tgaggacacg gccgtgtatt actgtgcgcg ttcgatttat 360
tactacgatg ccccgtttgc ttactggggc caagggactc tggtcaccgt ctctagtgcc 420
tccaccaagg gcccatcggt cttccccctg gcgccctgct ccaggagcac ctccgagagc 480
acagcggccc tgggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg 540
aactcaggcg ctctgaccag cggcgtgcac accttcccag ctgtcctaca gtcctcagga 600
ctctactccc tcagcagcgt ggtgaccgtg ccctccagca acttcggcac ccagacctac 660
acctgcaacg tagatcacaa gcccagcaac accaaggtgg acaagacagt tgagcgcaaa 720
tgttgtgtcg agtgcccacc gtgcccagca ccacctgtgg caggaccgtc agtcttcctc 780
ttccccccaa aacccaagga caccctcatg atctcccgga cccctgaggt cacgtgcgtg 840
gtggtggacg tgagccacga agaccccgag gtccagttca actggtacgt ggacggcgtg 900
gaggtgcata atgccaagac aaagccacgg gaggagcagt tcaacagcac gttccgtgtg 960
gtcagcgtcc tcaccgttgt gcaccaggac tggctgaacg gcaaggagta caagtgcaag 1020
gtctccaaca aaggcctccc agcccccatc gagaaaacca tctccaaaac caaagggcag 1080
ccccgagaac cacaggtgta caccctgccc ccatcccggg aggagatgac caagaaccag 1140
gtcagcctga cctgcctggt caaaggcttc taccccagcg acatcgccgt ggagtgggag 1200
agcaatgggc agccggagaa caactacaag accacacctc ccatgctgga ctccgacggc 1260
tccttcttcc tctacagcaa gctcaccgtg gacaagagca ggtggcagca ggggaacgtc 1320
ttctcatgct ccgtgatgca tgaggctctg cacaaccact acacgcagaa gagcctctcc 1380
ctgtctccgg gtaaa 1395
<210> 341
<211> 213
<212> PRT
<213> 家鼷鼠
<400> 341
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Ser Ser Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Ser Thr Ser Arg Leu Asn Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Asp Ile Lys His Pro Thr
85 90 95
Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro
100 105 110
Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr
115 120 125
Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys
130 135 140
Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu
145 150 155 160
Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser
165 170 175
Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala
180 185 190
Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe
195 200 205
Asn Arg Gly Glu Cys
210
<210> 342
<211> 639
<212> DNA
<213> 家鼷鼠
<400> 342
gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggtga ccgtgtcacc 60
atcacttgcc gcgcaagtca ggatattagc agctatttaa attggtatca gcagaaacca 120
gggaaagccc ctaagctcct gatctattct acttcccgtt tgaatagtgg ggtcccatca 180
cgcttcagtg gcagtggctc tgggacagat ttcactctca ccatcagcag tctgcaacct 240
gaagattttg caacttacta ctgtcaacag gatattaaac accctacgtt cggtcaaggc 300
accaaggtgg agatcaaacg tacggtggct gcaccatctg tcttcatctt cccgccatct 360
gatgagcagt tgaaatctgg aactgcctct gttgtgtgcc tgctgaataa cttctatccc 420
agagaggcca aagtacagtg gaaggtggat aacgccctcc aatcgggtaa ctcccaggag 480
agtgtcacag agcaggacag caaggacagc acctacagcc tcagcagcac cctgacgctg 540
agcaaagcag actacgagaa acacaaagtc tacgcctgcg aagtcaccca tcagggcctg 600
agctcgcccg tcacaaagag cttcaacagg ggagagtgt 639
<210> 343
<211> 235
<212> PRT
<213> 家鼷鼠
<400> 343
Met Asp Met Arg Val Pro Ala Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Arg Gly Ala Arg Cys Asp Ile Gln Met Thr Gln Ser Pro Ser Ser
20 25 30
Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser
35 40 45
Gln Asp Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys
50 55 60
Ala Pro Lys Leu Leu Ile Tyr Ser Thr Ser Arg Leu Asn Ser Gly Val
65 70 75 80
Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
85 90 95
Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln
100 105 110
Asp Ile Lys His Pro Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
115 120 125
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
130 135 140
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
145 150 155 160
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
165 170 175
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
180 185 190
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
195 200 205
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
210 215 220
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
225 230 235
<210> 344
<211> 705
<212> DNA
<213> 家鼷鼠
<400> 344
atggacatga gggtgcccgc tcagctcctg gggctcctgc tgctgtggct gagaggtgcc 60
agatgtgaca tccagatgac ccagtctcca tcctccctgt ctgcatctgt aggtgaccgt 120
gtcaccatca cttgccgcgc aagtcaggat attagcagct atttaaattg gtatcagcag 180
aaaccaggga aagcccctaa gctcctgatc tattctactt cccgtttgaa tagtggggtc 240
ccatcacgct tcagtggcag tggctctggg acagatttca ctctcaccat cagcagtctg 300
caacctgaag attttgcaac ttactactgt caacaggata ttaaacaccc tacgttcggt 360
caaggcacca aggtggagat caaacgtacg gtggctgcac catctgtctt catcttcccg 420
ccatctgatg agcagttgaa atctggaact gcctctgttg tgtgcctgct gaataacttc 480
tatcccagag aggccaaagt acagtggaag gtggataacg ccctccaatc gggtaactcc 540
caggagagtg tcacagagca ggacagcaag gacagcacct acagcctcag cagcaccctg 600
acgctgagca aagcagacta cgagaaacac aaagtctacg cctgcgaagt cacccatcag 660
ggcctgagct cgcccgtcac aaagagcttc aacaggggag agtgt 705
<210> 345
<211> 446
<212> PRT
<213> 家鼷鼠
<400> 345
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Phe Thr Phe Thr Asp Tyr
20 25 30
Ile Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Tyr Ile Asn Pro Tyr Asn Asp Asp Thr Glu Tyr Asn Glu Lys Phe
50 55 60
Lys Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Ser Ile Tyr Tyr Tyr Asp Ala Pro Phe Ala Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Asn Phe Gly Thr Gln Thr Tyr Thr Cys Asn Val Asp His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Thr Val Glu Arg Lys Cys Cys Val
210 215 220
Glu Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe
225 230 235 240
Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro
245 250 255
Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val
260 265 270
Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr
275 280 285
Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Val Val Ser Val
290 295 300
Leu Thr Val Val His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys
305 310 315 320
Lys Val Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser
325 330 335
Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro
340 345 350
Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val
355 360 365
Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly
370 375 380
Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Met Leu Asp Ser Asp
385 390 395 400
Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp
405 410 415
Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His
420 425 430
Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440 445
<210> 346
<211> 1338
<212> DNA
<213> 家鼷鼠
<400> 346
gaggtgcagc tggtgcagtc tggggctgag gtgaagaagc ctgggtcctc ggtgaaggtc 60
tcctgcaagg cttctggttt taccttcacc gactatatta tgcactgggt gcgtcaggcc 120
cctggtcaag ggcttgagtg gatgggctat atcaaccctt ataatgatga caccgaatac 180
aacgagaagt tcaagggccg tgtcacgatt accgcggaca aatccacgag cacagcctac 240
atggagctga gcagcctgcg ctctgaggac acggccgtgt attactgtgc gcgttcgatt 300
tattactacg atgccccgtt tgcttactgg ggccaaggga ctctggtcac cgtctctagt 360
gcctccacca agggcccatc ggtcttcccc ctggcgccct gctccaggag cacctccgag 420
agcacagcgg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg 480
tggaactcag gcgctctgac cagcggcgtg cacaccttcc cagctgtcct acagtcctca 540
ggactctact ccctcagcag cgtggtgacc gtgccctcca gcaacttcgg cacccagacc 600
tacacctgca acgtagatca caagcccagc aacaccaagg tggacaagac agttgagcgc 660
aaatgttgtg tcgagtgccc accgtgccca gcaccacctg tggcaggacc gtcagtcttc 720
ctcttccccc caaaacccaa ggacaccctc atgatctccc ggacccctga ggtcacgtgc 780
gtggtggtgg acgtgagcca cgaagacccc gaggtccagt tcaactggta cgtggacggc 840
gtggaggtgc ataatgccaa gacaaagcca cgggaggagc agttcaacag cacgttccgt 900
gtggtcagcg tcctcaccgt tgtgcaccag gactggctga acggcaagga gtacaagtgc 960
aaggtctcca acaaaggcct cccagccccc atcgagaaaa ccatctccaa aaccaaaggg 1020
cagccccgag aaccacaggt gtacaccctg cccccatccc gggaggagat gaccaagaac 1080
caggtcagcc tgacctgcct ggtcaaaggc ttctacccca gcgacatcgc cgtggagtgg 1140
gagagcaatg ggcagccgga gaacaactac aagaccacac ctcccatgct ggactccgac 1200
ggctccttct tcctctacag caagctcacc gtggacaaga gcaggtggca gcaggggaac 1260
gtcttctcat gctccgtgat gcatgaggct ctgcacaacc actacacgca gaagagcctc 1320
tccctgtctc cgggtaaa 1338
<210> 347
<211> 465
<212> PRT
<213> 家鼷鼠
<400> 347
Met Asp Trp Thr Trp Arg Ile Leu Phe Leu Val Ala Ala Ala Thr Gly
1 5 10 15
Ala His Ser Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys
20 25 30
Pro Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly Phe Thr Phe
35 40 45
Thr Asp Tyr Ile Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu
50 55 60
Glu Trp Met Gly Tyr Ile Asn Pro Tyr Asn Asp Asp Thr Glu Tyr Asn
65 70 75 80
Glu Lys Phe Lys Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser
85 90 95
Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Ser Ile Tyr Tyr Tyr Asp Ala Pro Phe Ala Tyr
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
130 135 140
Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser
145 150 155 160
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
165 170 175
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
180 185 190
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
195 200 205
Thr Val Pro Ser Ser Asn Phe Gly Thr Gln Thr Tyr Thr Cys Asn Val
210 215 220
Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Thr Val Glu Arg Lys
225 230 235 240
Cys Cys Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro
245 250 255
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
260 265 270
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
275 280 285
Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
290 295 300
Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Val
305 310 315 320
Val Ser Val Leu Thr Val Val His Gln Asp Trp Leu Asn Gly Lys Glu
325 330 335
Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu Lys
340 345 350
Thr Ile Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr
355 360 365
Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr
370 375 380
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu
385 390 395 400
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Met Leu
405 410 415
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys
420 425 430
Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu
435 440 445
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
450 455 460
Lys
465
<210> 348
<211> 1395
<212> DNA
<213> 家鼷鼠
<400> 348
atggactgga cctggaggat cctcttcttg gtggcagcag ccacaggagc ccactccgag 60
gtgcagctgg tgcagtctgg ggctgaggtg aagaagcctg ggtcctcggt gaaggtctcc 120
tgcaaggctt ctggttttac cttcaccgac tatattatgc actgggtgcg tcaggcccct 180
ggtcaagggc ttgagtggat gggctatatc aacccttata atgatgacac cgaatacaac 240
gagaagttca agggccgtgt cacgattacc gcggacaaat ccacgagcac agcctacatg 300
gagctgagca gcctgcgctc tgaggacacg gccgtgtatt actgtgcgcg ttcgatttat 360
tactacgatg ccccgtttgc ttactggggc caagggactc tggtcaccgt ctctagtgcc 420
tccaccaagg gcccatcggt cttccccctg gcgccctgct ccaggagcac ctccgagagc 480
acagcggccc tgggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg 540
aactcaggcg ctctgaccag cggcgtgcac accttcccag ctgtcctaca gtcctcagga 600
ctctactccc tcagcagcgt ggtgaccgtg ccctccagca acttcggcac ccagacctac 660
acctgcaacg tagatcacaa gcccagcaac accaaggtgg acaagacagt tgagcgcaaa 720
tgttgtgtcg agtgcccacc gtgcccagca ccacctgtgg caggaccgtc agtcttcctc 780
ttccccccaa aacccaagga caccctcatg atctcccgga cccctgaggt cacgtgcgtg 840
gtggtggacg tgagccacga agaccccgag gtccagttca actggtacgt ggacggcgtg 900
gaggtgcata atgccaagac aaagccacgg gaggagcagt tcaacagcac gttccgtgtg 960
gtcagcgtcc tcaccgttgt gcaccaggac tggctgaacg gcaaggagta caagtgcaag 1020
gtctccaaca aaggcctccc agcccccatc gagaaaacca tctccaaaac caaagggcag 1080
ccccgagaac cacaggtgta caccctgccc ccatcccggg aggagatgac caagaaccag 1140
gtcagcctga cctgcctggt caaaggcttc taccccagcg acatcgccgt ggagtgggag 1200
agcaatgggc agccggagaa caactacaag accacacctc ccatgctgga ctccgacggc 1260
tccttcttcc tctacagcaa gctcaccgtg gacaagagca ggtggcagca ggggaacgtc 1320
ttctcatgct ccgtgatgca tgaggctctg cacaaccact acacgcagaa gagcctctcc 1380
ctgtctccgg gtaaa 1395
<210> 349
<211> 417
<212> DNA
<213> 家鼷鼠
<400> 349
atggaatgga tctggatatt tctcttcctc ctgtcaggaa ctgcaggtgt ccactctgag 60
gtgcagctgg tgcagtctgg ggctgaggtg aagaagcctg ggtcctcggt gaaggtctcc 120
tgcaaggctt ctggttttac cttcaccgac tatattatgc actgggtgcg tcaggcccct 180
ggtcaagggc ttgagtggat gggctatatc aacccttata atgatgacac cgaatacaac 240
gagaagttca agggccgtgt cacgattacc gcggacaaat ccacgagcac agcctacatg 300
gagctgagca gcctgcgctc tgaggacacg gccgtgtatt actgtgcgcg ttcgatttat 360
tactacgatg ccccgtttgc ttactggggc caagggactc tggtcacagt ctcgagc 417
<210> 350
<211> 218
<212> PRT
<213> 家鼷鼠
<400> 350
Asp Ile Val Leu Thr Gln Ser Pro Ala Ser Leu Ala Val Ser Leu Gly
1 5 10 15
Gln Arg Ala Thr Ile Ala Cys Lys Ala Ser Gln Ser Val Asp Tyr Asp
20 25 30
Gly Thr Ser Tyr Met Asn Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro
35 40 45
Lys Leu Leu Ile Tyr Ala Ala Ser Asn Leu Glu Ser Glu Ile Pro Ala
50 55 60
Arg Phe Ser Gly Thr Gly Ser Gly Thr Asp Phe Thr Leu Asn Ile His
65 70 75 80
Pro Val Glu Glu Glu Asp Ile Thr Thr Tyr Tyr Cys Gln Gln Ser Asn
85 90 95
Glu Asp Pro Phe Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg
100 105 110
Ala Asp Ala Ala Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln
115 120 125
Leu Thr Ser Gly Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr
130 135 140
Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln
145 150 155 160
Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr
165 170 175
Tyr Ser Met Ser Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg
180 185 190
His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro
195 200 205
Ile Val Lys Ser Phe Asn Arg Asn Glu Cys
210 215
<210> 351
<211> 15
<212> PRT
<213> 家鼷鼠
<400> 351
Lys Ala Ser Gln Ser Val Asp Tyr Asp Gly Thr Ser Tyr Met Asn
1 5 10 15
<210> 352
<211> 7
<212> PRT
<213> 家鼷鼠
<400> 352
Ala Ala Ser Asn Leu Glu Ser
1 5
<210> 353
<211> 9
<212> PRT
<213> 家鼷鼠
<400> 353
Gln Gln Ser Asn Glu Asp Pro Phe Thr
1 5
<210> 354
<211> 657
<212> DNA
<213> 家鼷鼠
<400> 354
gacattgtgt tgacccagtc tccagcttct ttggctgtgt ctctagggca gagggccacc 60
atcgcctgca aggccagcca aagtgttgat tatgatggta ctagttatat gaattggtac 120
caacagaaac caggacagcc acccaaactc ctcatctatg ctgcatccaa tctagaatct 180
gagatcccag ccaggtttag tggcactggg tctgggacag acttcaccct caacatccat 240
cctgtggagg aggaggatat cacaacctat tactgtcagc aaagtaatga ggatccgttc 300
acgttcggag gggggaccaa gttggaaata aaacgggctg atgctgcacc aactgtatcc 360
atcttcccac catccagtga gcagttaaca tctggaggtg cctcagtcgt gtgcttcttg 420
aacaacttct accccaaaga catcaatgtc aagtggaaga ttgatggcag tgaacgacaa 480
aatggcgtcc tgaacagttg gactgatcag gacagcaaag acagcaccta cagcatgagc 540
agcaccctca cgttgaccaa ggacgagtat gaacgacata acagctatac ctgtgaggcc 600
actcacaaga catcaacttc acccattgtc aagagcttca acaggaatga gtgttag 657
<210> 355
<211> 238
<212> PRT
<213> 家鼷鼠
<400> 355
Met Glu Thr Asp Thr Ile Leu Leu Trp Val Leu Leu Leu Trp Val Pro
1 5 10 15
Gly Ser Thr Gly Asp Ile Val Leu Thr Gln Ser Pro Ala Ser Leu Ala
20 25 30
Val Ser Leu Gly Gln Arg Ala Thr Ile Ala Cys Lys Ala Ser Gln Ser
35 40 45
Val Asp Tyr Asp Gly Thr Ser Tyr Met Asn Trp Tyr Gln Gln Lys Pro
50 55 60
Gly Gln Pro Pro Lys Leu Leu Ile Tyr Ala Ala Ser Asn Leu Glu Ser
65 70 75 80
Glu Ile Pro Ala Arg Phe Ser Gly Thr Gly Ser Gly Thr Asp Phe Thr
85 90 95
Leu Asn Ile His Pro Val Glu Glu Glu Asp Ile Thr Thr Tyr Tyr Cys
100 105 110
Gln Gln Ser Asn Glu Asp Pro Phe Thr Phe Gly Gly Gly Thr Lys Leu
115 120 125
Glu Ile Lys Arg Ala Asp Ala Ala Pro Thr Val Ser Ile Phe Pro Pro
130 135 140
Ser Ser Glu Gln Leu Thr Ser Gly Gly Ala Ser Val Val Cys Phe Leu
145 150 155 160
Asn Asn Phe Tyr Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly
165 170 175
Ser Glu Arg Gln Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser
180 185 190
Lys Asp Ser Thr Tyr Ser Met Ser Ser Thr Leu Thr Leu Thr Lys Asp
195 200 205
Glu Tyr Glu Arg His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr
210 215 220
Ser Thr Ser Pro Ile Val Lys Ser Phe Asn Arg Asn Glu Cys
225 230 235
<210> 356
<211> 717
<212> DNA
<213> 家鼷鼠
<400> 356
atggagacag acacaatcct gctatgggtg ctgctgctct gggttccagg ctccactggt 60
gacattgtgt tgacccagtc tccagcttct ttggctgtgt ctctagggca gagggccacc 120
atcgcctgca aggccagcca aagtgttgat tatgatggta ctagttatat gaattggtac 180
caacagaaac caggacagcc acccaaactc ctcatctatg ctgcatccaa tctagaatct 240
gagatcccag ccaggtttag tggcactggg tctgggacag acttcaccct caacatccat 300
cctgtggagg aggaggatat cacaacctat tactgtcagc aaagtaatga ggatccgttc 360
acgttcggag gggggaccaa gttggaaata aaacgggctg atgctgcacc aactgtatcc 420
atcttcccac catccagtga gcagttaaca tctggaggtg cctcagtcgt gtgcttcttg 480
aacaacttct accccaaaga catcaatgtc aagtggaaga ttgatggcag tgaacgacaa 540
aatggcgtcc tgaacagttg gactgatcag gacagcaaag acagcaccta cagcatgagc 600
agcaccctca cgttgaccaa ggacgagtat gaacgacata acagctatac ctgtgaggcc 660
actcacaaga catcaacttc acccattgtc aagagcttca acaggaatga gtgttag 717
<210> 357
<211> 442
<212> PRT
<213> 家鼷鼠
<400> 357
Gln Val Gln Leu Gln Gln Pro Gly Thr Glu Leu Val Arg Pro Gly Thr
1 5 10 15
Ser Val Lys Leu Ser Cys Lys Ala Ser Gly Tyr Ile Phe Thr Thr Tyr
20 25 30
Trp Met Asn Trp Val Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Met Ile His Pro Ser Ala Ser Glu Ile Arg Leu Asp Gln Lys Phe
50 55 60
Lys Asp Lys Ala Thr Leu Thr Leu Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met His Leu Ser Gly Pro Thr Ser Val Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Ser Gly Glu Trp Gly Ser Met Asp Tyr Trp Gly Gln Gly Thr
100 105 110
Ser Val Thr Val Ser Ser Ala Lys Thr Thr Pro Pro Ser Val Tyr Pro
115 120 125
Leu Ala Pro Gly Ser Ala Ala Gln Thr Asn Ser Met Val Thr Leu Gly
130 135 140
Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val Thr Val Thr Trp Asn
145 150 155 160
Ser Gly Ser Leu Ser Ser Gly Val His Thr Phe Pro Ala Val Leu Gln
165 170 175
Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr Val Pro Ser Ser Thr
180 185 190
Trp Pro Ser Glu Thr Val Thr Cys Asn Val Ala His Pro Ala Ser Ser
195 200 205
Thr Lys Val Asp Lys Lys Ile Val Pro Arg Asp Cys Gly Cys Lys Pro
210 215 220
Cys Ile Cys Thr Val Pro Glu Val Ser Ser Val Phe Ile Phe Pro Pro
225 230 235 240
Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro Lys Val Thr Cys
245 250 255
Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu Val Gln Phe Ser Trp
260 265 270
Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr Gln Pro Arg Glu
275 280 285
Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser Glu Leu Pro Ile Met
290 295 300
His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg Val Asn Ser
305 310 315 320
Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly
325 330 335
Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro Lys Glu Gln
340 345 350
Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile Thr Asp Phe Phe
355 360 365
Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly Gln Pro Ala Glu
370 375 380
Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr Asp Gly Ser Tyr Phe
385 390 395 400
Ile Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn Trp Glu Ala Gly Asn
405 410 415
Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His Asn His His Thr
420 425 430
Glu Lys Ser Leu Ser His Ser Pro Gly Lys
435 440
<210> 358
<211> 5
<212> PRT
<213> 家鼷鼠
<400> 358
Thr Tyr Trp Met Asn
1 5
<210> 359
<211> 17
<212> PRT
<213> 家鼷鼠
<400> 359
Met Ile His Pro Ser Ala Ser Glu Ile Arg Leu Asp Gln Lys Phe Lys
1 5 10 15
Asp
<210> 360
<211> 9
<212> PRT
<213> 家鼷鼠
<400> 360
Ser Gly Glu Trp Gly Ser Met Asp Tyr
1 5
<210> 361
<211> 1329
<212> DNA
<213> 家鼷鼠
<400> 361
caggtccaac tacagcagcc tgggactgag ctggtgaggc ctggaacttc agtgaagttg 60
tcctgtaagg cttctggcta catcttcacc acctactgga tgaactgggt gaaacagagg 120
cctggacaag gccttgagtg gattggcatg attcatcctt ccgcaagtga aattaggttg 180
gatcagaaat tcaaggacaa ggccacattg actcttgaca aatcctccag cacagcctat 240
atgcacctca gcggcccgac atctgtggat tctgcggtct attactgtgc aagatcaggg 300
gaatgggggt ctatggacta ctggggtcaa ggaacctcag tcaccgtctc ctcagccaaa 360
acgacacccc catctgtcta tccactggcc cctggatctg ctgcccaaac taactccatg 420
gtgaccctgg gatgcctggt caagggctat ttccctgagc cagtgacagt gacctggaac 480
tctggatccc tgtccagcgg tgtgcacacc ttcccagctg tcctgcagtc tgacctctac 540
actctgagca gctcagtgac tgtcccctcc agcacctggc ccagcgagac cgtcacctgc 600
aacgttgccc acccggccag cagcaccaag gtggacaaga aaattgtgcc cagggattgt 660
ggttgtaagc cttgcatatg tacagtccca gaagtatcat ctgtcttcat cttcccccca 720
aagcccaagg atgtgctcac cattactctg actcctaagg tcacgtgtgt tgtggtagac 780
atcagcaagg atgatcccga ggtccagttc agctggtttg tagatgatgt ggaggtgcac 840
acagctcaga cgcaaccccg ggaggagcag ttcaacagca ctttccgctc agtcagtgaa 900
cttcccatca tgcaccagga ctggctcaat ggcaaggagt tcaaatgcag ggtcaacagt 960
gcagctttcc ctgcccccat cgagaaaacc atctccaaaa ccaaaggcag accgaaggct 1020
ccacaggtgt acaccattcc acctcccaag gagcagatgg ccaaggataa agtcagtctg 1080
acctgcatga taacagactt cttccctgaa gacattactg tggagtggca gtggaatggg 1140
cagccagcgg agaactacaa gaacactcag cccatcatgg acacagatgg ctcttacttc 1200
atctacagca agctcaatgt gcagaagagc aactgggagg caggaaatac tttcacctgc 1260
tctgtgttac atgagggcct gcacaaccac catactgaga agagcctctc ccactctcct 1320
ggtaaatga 1329
<210> 362
<211> 461
<212> PRT
<213> 家鼷鼠
<400> 362
Met Gly Trp Ser Ser Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Gly
1 5 10 15
Val His Ser Gln Val Gln Leu Gln Gln Pro Gly Thr Glu Leu Val Arg
20 25 30
Pro Gly Thr Ser Val Lys Leu Ser Cys Lys Ala Ser Gly Tyr Ile Phe
35 40 45
Thr Thr Tyr Trp Met Asn Trp Val Lys Gln Arg Pro Gly Gln Gly Leu
50 55 60
Glu Trp Ile Gly Met Ile His Pro Ser Ala Ser Glu Ile Arg Leu Asp
65 70 75 80
Gln Lys Phe Lys Asp Lys Ala Thr Leu Thr Leu Asp Lys Ser Ser Ser
85 90 95
Thr Ala Tyr Met His Leu Ser Gly Pro Thr Ser Val Asp Ser Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Ser Gly Glu Trp Gly Ser Met Asp Tyr Trp Gly
115 120 125
Gln Gly Thr Ser Val Thr Val Ser Ser Ala Lys Thr Thr Pro Pro Ser
130 135 140
Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr Asn Ser Met Val
145 150 155 160
Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val Thr Val
165 170 175
Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr Phe Pro Ala
180 185 190
Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr Val Pro
195 200 205
Ser Ser Thr Trp Pro Ser Glu Thr Val Thr Cys Asn Val Ala His Pro
210 215 220
Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val Pro Arg Asp Cys Gly
225 230 235 240
Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser Ser Val Phe Ile
245 250 255
Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro Lys
260 265 270
Val Thr Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu Val Gln
275 280 285
Phe Ser Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr Gln
290 295 300
Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser Glu Leu
305 310 315 320
Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg
325 330 335
Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys
340 345 350
Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro
355 360 365
Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile Thr
370 375 380
Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly Gln
385 390 395 400
Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr Asp Gly
405 410 415
Ser Tyr Phe Ile Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn Trp Glu
420 425 430
Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His Asn
435 440 445
His His Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys
450 455 460
<210> 363
<211> 1386
<212> DNA
<213> 家鼷鼠
<400> 363
atgggatgga gctctatcat cctcttcttg gtagcaacag ctacaggtgt ccactcccag 60
gtccaactac agcagcctgg gactgagctg gtgaggcctg gaacttcagt gaagttgtcc 120
tgtaaggctt ctggctacat cttcaccacc tactggatga actgggtgaa acagaggcct 180
ggacaaggcc ttgagtggat tggcatgatt catccttccg caagtgaaat taggttggat 240
cagaaattca aggacaaggc cacattgact cttgacaaat cctccagcac agcctatatg 300
cacctcagcg gcccgacatc tgtggattct gcggtctatt actgtgcaag atcaggggaa 360
tgggggtcta tggactactg gggtcaagga acctcagtca ccgtctcctc agccaaaacg 420
acacccccat ctgtctatcc actggcccct ggatctgctg cccaaactaa ctccatggtg 480
accctgggat gcctggtcaa gggctatttc cctgagccag tgacagtgac ctggaactct 540
ggatccctgt ccagcggtgt gcacaccttc ccagctgtcc tgcagtctga cctctacact 600
ctgagcagct cagtgactgt cccctccagc acctggccca gcgagaccgt cacctgcaac 660
gttgcccacc cggccagcag caccaaggtg gacaagaaaa ttgtgcccag ggattgtggt 720
tgtaagcctt gcatatgtac agtcccagaa gtatcatctg tcttcatctt ccccccaaag 780
cccaaggatg tgctcaccat tactctgact cctaaggtca cgtgtgttgt ggtagacatc 840
agcaaggatg atcccgaggt ccagttcagc tggtttgtag atgatgtgga ggtgcacaca 900
gctcagacgc aaccccggga ggagcagttc aacagcactt tccgctcagt cagtgaactt 960
cccatcatgc accaggactg gctcaatggc aaggagttca aatgcagggt caacagtgca 1020
gctttccctg cccccatcga gaaaaccatc tccaaaacca aaggcagacc gaaggctcca 1080
caggtgtaca ccattccacc tcccaaggag cagatggcca aggataaagt cagtctgacc 1140
tgcatgataa cagacttctt ccctgaagac attactgtgg agtggcagtg gaatgggcag 1200
ccagcggaga actacaagaa cactcagccc atcatggaca cagatggctc ttacttcatc 1260
tacagcaagc tcaatgtgca gaagagcaac tgggaggcag gaaatacttt cacctgctct 1320
gtgttacatg agggcctgca caaccaccat actgagaaga gcctctccca ctctcctggt 1380
aaatga 1386
<210> 364
<211> 106
<212> PRT
<213> 家鼷鼠
<400> 364
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Ser Ser Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Ser Thr Ser Arg Leu Asn Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Asp Ile Lys His Pro Thr
85 90 95
Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 365
<211> 318
<212> DNA
<213> 家鼷鼠
<400> 365
gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggtga ccgtgtcacc 60
atcacttgcc gcgcaagtca ggatattagc agctatttaa attggtatca gcagaaacca 120
gggaaagccc ctaagctcct gatctattct acttcccgtt tgaatagtgg ggtcccatca 180
cgcttcagtg gcagtggctc tgggacagat ttcactctca ccatcagcag tctgcaacct 240
gaagattttg caacttacta ctgtcaacag gatattaaac accctacgtt cggtcaaggc 300
accaaggtgg agatcaaa 318
<210> 366
<211> 120
<212> PRT
<213> 家鼷鼠
<400> 366
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Phe Thr Phe Thr Asp Tyr
20 25 30
Ile Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Tyr Ile Asn Pro Tyr Asn Asp Asp Thr Glu Tyr Asn Glu Lys Phe
50 55 60
Lys Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Ser Ile Tyr Tyr Tyr Asp Ala Pro Phe Ala Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 367
<211> 360
<212> DNA
<213> 家鼷鼠
<400> 367
gaggtgcagc tggtgcagtc tggggctgag gtgaagaagc ctgggtcctc ggtgaaggtc 60
tcctgcaagg cttctggttt taccttcacc gactatatta tgcactgggt gcgtcaggcc 120
cctggtcaag ggcttgagtg gatgggctat atcaaccctt ataatgatga caccgaatac 180
aacgagaagt tcaagggccg tgtcacgatt accgcggaca aatccacgag cacagcctac 240
atggagctga gcagcctgcg ctctgaggac acggccgtgt attactgtgc gcgttcgatt 300
tattactacg atgccccgtt tgcttactgg ggccaaggga ctctggtcac cgtctctagt 360
<210> 368
<211> 108
<212> PRT
<213> 家鼷鼠
<400> 368
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Phe Thr Ala
20 25 30
Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Ser Ser Tyr Pro Leu
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
100 105
<210> 369
<211> 324
<212> DNA
<213> 家鼷鼠
<400> 369
gatatccaga tgacccagag cccgagcagc ctgagcgcga gcgtgggcga tcgcgtgacc 60
attacctgca aagcgagcca ggatgtgttt accgcggtgg cgtggtatca gcagaaaccg 120
ggcaaagcgc cgaaactgct gatttattgg gcgagcaccc gccataccgg cgtgccgagt 180
cgctttagcg gcagcggcag cggcaccgat tttaccctga ccattagcag cctgcagccg 240
gaagattttg cgacctatta ttgccagcag tatagcagct atccgctgac ctttggcggc 300
ggcaccaaag tggaaattaa acgt 324
<210> 370
<211> 119
<212> PRT
<213> 家鼷鼠
<400> 370
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Phe Asn Ile Lys Asp Tyr
20 25 30
Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Arg Ile Asp Pro Glu Asn Gly Asp Ile Ile Tyr Asp Pro Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Tyr Asp Ala Gly Asp Pro Ala Trp Phe Thr Tyr Trp Gly Gln Gly
100 105 110
Thr Leu Val Thr Val Ser Ser
115
<210> 371
<211> 357
<212> DNA
<213> 家鼷鼠
<400> 371
gaagtgcagc tggtgcagag cggcgcggaa gtgaaaaaac cgggcgcgag cgtgaaagtg 60
agctgcaaag cgagcggctt taacattaaa gattattata tgcattgggt gcgccaggcg 120
ccgggccagg gcctggaatg gatcggccgc attgatccgg aaaacggcga tattatttat 180
gatccgaaat ttcagggccg cgtgaccatg accaccgata ccagcaccag caccgcgtat 240
atggaactgc gcagcctgcg cagcgatgat accgcggtgt attattgcgc gtatgatgcg 300
ggcgatccgg cgtggtttac ctattggggc cagggcaccc tggtgaccgt ctcgagc 357
<210> 372
<211> 108
<212> PRT
<213> 家鼷鼠
<400> 372
Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Ser Val Ser Ser Ser Ile Ser Ser Ser
20 25 30
Asn Leu His Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu
35 40 45
Ile Tyr Gly Thr Ser Asn Leu Ala Ser Gly Val Pro 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
Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Trp Thr Thr Thr Tyr
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg
100 105
<210> 373
<211> 324
<212> DNA
<213> 家鼷鼠
<400> 373
gatattcagc tgacccagag cccgagcttt ctgagcgcga gcgtgggcga tcgcgtgacc 60
attacctgca gcgtgagcag cagcattagc agcagcaacc tgcattggta tcagcagaaa 120
ccgggcaaag cgccgaaact gctgatttat ggcaccagca acctggcgag cggcgtgccg 180
agccgcttta gcggcagcgg cagcggcacc gaatttaccc tgaccattag cagcctgcag 240
ccggaagatt ttgcgaccta ttattgccag cagtggacca ccacctatac ctttggccag 300
ggcaccaaac tggaaattaa acgt 324
<210> 374
<211> 122
<212> PRT
<213> 家鼷鼠
<400> 374
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Phe Asn Ile Lys Asp Tyr
20 25 30
Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Arg Ile Asp Pro Asp Asn Gly Glu Ser Thr Tyr Val Pro Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Gly Leu Asp Tyr Gly Asp Tyr Tyr Ala Val Asp Tyr Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 375
<211> 366
<212> DNA
<213> 家鼷鼠
<400> 375
gaagtgcagc tggtgcagag cggcgcggaa gtgaaaaaac cgggcgcgag cgtgaaagtg 60
agctgcaaag cgagcggctt taacattaaa gattattata ttcattgggt gcgccaggcg 120
ccgggccagg gcctggaatg gatgggccgc attgatccgg ataacggcga aagcacctat 180
gtgccgaaat ttcagggccg cgtgaccatg accaccgata ccagcaccag caccgcgtat 240
atggaactgc gcagcctgcg cagcgatgat accgcggtgt attattgcgc gcgcgaaggc 300
ctggattatg gcgattatta tgcggtggat tattggggcc agggcaccct ggtgaccgtc 360
tcgagc 366
<210> 376
<211> 107
<212> PRT
<213> 家鼷鼠
<400> 376
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Ser Asn Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Tyr Thr Ser Arg Leu Leu Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Asp Thr Leu Pro Tyr
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105
<210> 377
<211> 321
<212> DNA
<213> 家鼷鼠
<400> 377
gacatccaga tgacccagtc tccatcctcc ctctccgcat ccgtaggcga ccgcgtaacc 60
ataacatgta gagcatctca agatatttcc aactatttga attggtacca acaaaaaccc 120
ggcaaagcac ctaaactcct catttactat acatcaagac tcctctccgg cgttccatca 180
cgattctcag gctccggctc cggcacagat ttcacactca ctatttcctc cctccaacca 240
gaagattttg caacctatta ctgtcaacaa ggcgatacac tcccatacac attcggcggc 300
ggcacaaaag ttgaaattaa a 321
<210> 378
<211> 123
<212> PRT
<213> 家鼷鼠
<400> 378
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Asn Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Glu Ile Asn Pro Asn Ser Gly Gly Ala Gly Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Leu Gly Tyr Asp Asp Ile Tyr Asp Asp Trp Tyr Phe Asp Val
100 105 110
Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 379
<211> 369
<212> DNA
<213> 家鼷鼠
<400> 379
gaggtgcagc tggtgcagag cggcgccgag gtaaaaaaac caggagcaag cgttaaagtt 60
tcttgtaaag caagcggata tacatttaca gattacaaca tgcattgggt aagacaagcg 120
ccaggacaag gattggaatg gatgggcgaa attaacccta atagtggagg agcaggctac 180
aatcaaaaat tcaaagggag agttacaatg acaacagaca caagcacttc aacagcatat 240
atggaactgc gatcacttag aagcgacgat acagctgtat actattgcgc acgacttggg 300
tatgatgata tatatgatga ctggtatttc gatgtttggg gccagggaac aacagttacc 360
gtctctagt 369
<210> 380
<211> 108
<212> PRT
<213> 家鼷鼠
<400> 380
Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Ser Ser Val Thr Ser Ser
20 25 30
Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu
35 40 45
Ile Tyr Ser Thr Ser Asn Leu Ala Ser Gly Val Pro 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
Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Asp Phe Phe Pro
85 90 95
Ser Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105
<210> 381
<211> 324
<212> DNA
<213> 家鼷鼠
<400> 381
gacatccagc tgacccagag ccccagcttc ctttccgcat ccgttggtga ccgagtaaca 60
atcacatgcc gcgcctcatc ttcagttaca tcttcttatc ttaattggta tcaacaaaaa 120
ccaggaaaag cacctaaact tcttatatac tctacatcta atctcgcatc aggagttccc 180
tctcgatttt caggatctgg atcaggcaca gaatttacac ttactatatc atcactccaa 240
ccagaagact tcgccactta ttactgccaa caatacgatt tttttccaag cacattcgga 300
ggaggtacaa aagtagaaat caag 324
<210> 382
<211> 121
<212> PRT
<213> 家鼷鼠
<400> 382
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Tyr Met Asn Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Met
35 40 45
Gly Asp Ile Asn Pro Tyr Asn Asp Asp Thr Thr Tyr Asn His Lys Phe
50 55 60
Lys Gly Arg Val Thr Ile Thr Arg Asp Thr Ser Ala Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Thr Ala Val Ile Thr Thr Asn Ala Met Asp Tyr Trp Gly
100 105 110
Gln Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 383
<211> 363
<212> DNA
<213> 家鼷鼠
<400> 383
gaggtgcagc tggtgcagag cggcgccgag gtcaagaaac ctggagcaag cgtaaaggtt 60
agttgcaaag catctggata cacatttacc gactactaca tgaattgggt acgacaagcc 120
cctggacaaa gacttgaatg gatgggagac attaaccctt ataacgacga cactacatac 180
aatcataaat ttaaaggaag agttacaatt acaagagata catccgcatc aaccgcctat 240
atggaacttt cctcattgag atctgaagac actgctgttt attactgtgc aagagaaact 300
gccgttatta ctactaacgc tatggattac tggggtcaag gaaccactgt taccgtctct 360
agt 363
<210> 384
<211> 108
<212> PRT
<213> 家鼷鼠
<400> 384
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Ser Val Ser Ser Thr Ile Ser Ser Asn
20 25 30
His Leu His Trp Phe Gln Gln Lys Pro Gly Lys Ala Pro Lys Ser Leu
35 40 45
Ile Tyr Gly Thr Ser Asn Leu Ala Ser Gly Val Pro Ser Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln
65 70 75 80
Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Trp Ser Ser Tyr Pro
85 90 95
Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105
<210> 385
<211> 324
<212> DNA
<213> 家鼷鼠
<400> 385
gacatccaga tgacccagtc tccatcctcc ctctcagcat ccgtaggcga tagagttaca 60
ataacatgca gcgtatcatc aactatatca tcaaatcatc ttcattggtt ccaacagaaa 120
cccggcaaag cacctaaatc acttatatac ggcacatcaa atctcgcatc aggcgttcct 180
tcaagatttt caggctctgg ctcaggcacc gactttactc ttacaatatc ctccctccaa 240
cccgaagact tcgcaaccta ttactgtcaa caatggtcct catatccact cacatttggc 300
ggcggcacaa aagtagaaat taaa 324
<210> 386
<211> 125
<212> PRT
<213> 家鼷鼠
<400> 386
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Asp Phe Asn Ile Lys Asp Phe
20 25 30
Tyr Leu His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Arg Ile Asp Pro Glu Asn Gly Asp Thr Leu Tyr Asp Pro Lys Phe
50 55 60
Gln Asp Lys Val Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Ala Asp Tyr Phe His Asp Gly Thr Ser Tyr Trp Tyr Phe
100 105 110
Asp Val Trp Gly Arg Gly Thr Leu Val Thr Val Ser Ser
115 120 125
<210> 387
<211> 375
<212> DNA
<213> 家鼷鼠
<400> 387
gaggtgcagc tggtgcagtc tggggctgag gtgaagaagc ctggggcctc agtgaaggtc 60
tcctgcaagg cttctgactt caacattaaa gacttctatc tacactgggt gcgacaggcc 120
cctggacaag ggcttgagtg gattggaagg attgatcctg agaatggtga tactttatat 180
gacccgaagt tccaggacaa ggtcaccatg accacagaca cgtccaccag cacagcctac 240
atggagctga ggagcctgag atctgacgac acggccgtgt attactgtgc gagagaggcg 300
gattatttcc acgatggtac ctcctactgg tacttcgatg tctggggccg tggcaccctg 360
gtcaccgtct ctagt 375
<210> 388
<211> 106
<212> PRT
<213> 家鼷鼠
<400> 388
Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Ser Ser Ile Ser Tyr Ile
20 25 30
His Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr
35 40 45
Ala Thr Ser Asn Leu Ala Ser Gly Val Pro Ser Arg Phe Ser Gly Ser
50 55 60
Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu
65 70 75 80
Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Trp Ser Ser Asp Pro Leu Thr
85 90 95
Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105
<210> 389
<211> 318
<212> DNA
<213> 家鼷鼠
<400> 389
gacatccagt tgacccagtc tccatccttc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgca gggccagctc aagtataagt tacatacact ggtatcagca aaaaccaggg 120
aaagccccta agctcctgat ctatgccaca tccaacctgg cttctggggt cccatcaagg 180
ttcagcggca gtggatctgg gacagaattc actctcacaa tcagcagcct gcagcctgaa 240
gattttgcaa cttattactg tcagcagtgg agtagtgacc cactcacgtt cggcggaggg 300
accaaggtgg agatcaaa 318
<210> 390
<211> 121
<212> PRT
<213> 家鼷鼠
<400> 390
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Phe Asp Ile Lys Asp Tyr
20 25 30
Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Arg Val Asp Pro Asp Asn Gly Glu Thr Glu Phe Ala Pro Lys Phe
50 55 60
Pro Gly Lys Val Thr Met Thr Thr Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Asp Tyr Asp Gly Thr Tyr Thr Trp Phe Pro Tyr Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 391
<211> 363
<212> DNA
<213> 家鼷鼠
<400> 391
gaggtgcagc tggtgcagtc tggggctgag gtgaagaagc ctggggcctc agtgaaggtc 60
tcctgcaagg cttctggatt cgacattaag gactactata tacactgggt gcgacaggcc 120
cctggacaag ggcttgagtg gatcggaagg gttgatcctg acaatggtga gactgaattt 180
gccccgaagt tcccgggcaa ggtcaccatg accacagaca cgtccatcag cacagcctac 240
atggagctga gcaggctgag atctgacgac acggccgtgt attactgtgc gagagaagac 300
tacgatggta cctacacctg gtttccttat tggggccaag ggactctggt caccgtctct 360
agt 363
<210> 392
<211> 448
<212> PRT
<213> 人工序列
<220>
<223> 合成多肽
<220>
<221> MISC_FEATURE
<223> 人源化抗体序列
<400> 392
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Asn Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Glu Ile Asn Pro Asn Ser Gly Gly Ala Gly Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Leu Gly Tyr Asp Asp Ile Tyr Asp Asp Trp Tyr Phe Asp Val
100 105 110
Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly
115 120 125
Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser
130 135 140
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
145 150 155 160
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
165 170 175
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
180 185 190
Thr Val Pro Ser Ser Asn Phe Gly Thr Gln Thr Tyr Thr Cys Asn Val
195 200 205
Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Thr Val Glu Arg Lys
210 215 220
Cys Cys Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro
225 230 235 240
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
245 250 255
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
260 265 270
Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
275 280 285
Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Val
290 295 300
Val Ser Val Leu Thr Val Val His Gln Asp Trp Leu Asn Gly Lys Glu
305 310 315 320
Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu Lys
325 330 335
Thr Ile Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr
340 345 350
Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr
355 360 365
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu
370 375 380
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Met Leu
385 390 395 400
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys
405 410 415
Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu
420 425 430
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
435 440 445
<210> 393
<211> 446
<212> PRT
<213> 人工序列
<220>
<223> 合成多肽
<220>
<221> MISC_FEATURE
<223> 人源化抗体序列
<400> 393
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Tyr Met Asn Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Met
35 40 45
Gly Asp Ile Asn Pro Tyr Asn Asp Asp Thr Thr Tyr Asn His Lys Phe
50 55 60
Lys Gly Arg Val Thr Ile Thr Arg Asp Thr Ser Ala Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Thr Ala Val Ile Thr Thr Asn Ala Met Asp Tyr Trp Gly
100 105 110
Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser
115 120 125
Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala
130 135 140
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val
145 150 155 160
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala
165 170 175
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val
180 185 190
Pro Ser Ser Asn Phe Gly Thr Gln Thr Tyr Thr Cys Asn Val Asp His
195 200 205
Lys Pro Ser Asn Thr Lys Val Asp Lys Thr Val Glu Arg Lys Cys Cys
210 215 220
Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val
225 230 235 240
Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr
245 250 255
Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu
260 265 270
Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys
275 280 285
Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Val Val Ser
290 295 300
Val Leu Thr Val Val His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys
305 310 315 320
Cys Lys Val Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu Lys Thr Ile
325 330 335
Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro
340 345 350
Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu
355 360 365
Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn
370 375 380
Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Met Leu Asp Ser
385 390 395 400
Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg
405 410 415
Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu
420 425 430
His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
435 440 445
<210> 394
<211> 450
<212> PRT
<213> 人工序列
<220>
<223> 合成多肽
<220>
<221> MISC_FEATURE
<223> 人源化抗体序列
<400> 394
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Asp Phe Asn Ile Lys Asp Phe
20 25 30
Tyr Leu His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Arg Ile Asp Pro Glu Asn Gly Asp Thr Leu Tyr Asp Pro Lys Phe
50 55 60
Gln Asp Lys Val Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Ala Asp Tyr Phe His Asp Gly Thr Ser Tyr Trp Tyr Phe
100 105 110
Asp Val Trp Gly Arg Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr
115 120 125
Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser
130 135 140
Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu
145 150 155 160
Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His
165 170 175
Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser
180 185 190
Val Val Thr Val Pro Ser Ser Asn Phe Gly Thr Gln Thr Tyr Thr Cys
195 200 205
Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Thr Val Glu
210 215 220
Arg Lys Cys Cys Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val Ala
225 230 235 240
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
245 250 255
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
260 265 270
Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val
275 280 285
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe
290 295 300
Arg Val Val Ser Val Leu Thr Val Val His Gln Asp Trp Leu Asn Gly
305 310 315 320
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ala Pro Ile
325 330 335
Glu Lys Thr Ile Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln Val
340 345 350
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
355 360 365
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
370 375 380
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
385 390 395 400
Met Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
405 410 415
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
420 425 430
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
435 440 445
Pro Gly
450
<210> 395
<211> 446
<212> PRT
<213> 人工序列
<220>
<223> 合成多肽
<220>
<221> MISC_FEATURE
<223> 人源化抗体序列
<400> 395
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Phe Asp Ile Lys Asp Tyr
20 25 30
Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Arg Val Asp Pro Asp Asn Gly Glu Thr Glu Phe Ala Pro Lys Phe
50 55 60
Pro Gly Lys Val Thr Met Thr Thr Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Asp Tyr Asp Gly Thr Tyr Thr Trp Phe Pro Tyr Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser
115 120 125
Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala
130 135 140
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val
145 150 155 160
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala
165 170 175
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val
180 185 190
Pro Ser Ser Asn Phe Gly Thr Gln Thr Tyr Thr Cys Asn Val Asp His
195 200 205
Lys Pro Ser Asn Thr Lys Val Asp Lys Thr Val Glu Arg Lys Cys Cys
210 215 220
Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val
225 230 235 240
Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr
245 250 255
Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu
260 265 270
Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys
275 280 285
Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Val Val Ser
290 295 300
Val Leu Thr Val Val His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys
305 310 315 320
Cys Lys Val Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu Lys Thr Ile
325 330 335
Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro
340 345 350
Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu
355 360 365
Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn
370 375 380
Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Met Leu Asp Ser
385 390 395 400
Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg
405 410 415
Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu
420 425 430
His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
435 440 445
<210> 396
<211> 445
<212> PRT
<213> 人工序列
<220>
<223> 合成多肽
<220>
<221> MISC_FEATURE
<223> 人源化抗体序列
<400> 396
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Phe Thr Phe Thr Asp Tyr
20 25 30
Ile Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Tyr Ile Asn Pro Tyr Asn Asp Asp Thr Glu Tyr Asn Glu Lys Phe
50 55 60
Lys Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Ser Ile Tyr Tyr Tyr Asp Ala Pro Phe Ala Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Asn Phe Gly Thr Gln Thr Tyr Thr Cys Asn Val Asp His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Thr Val Glu Arg Lys Cys Cys Val
210 215 220
Glu Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe
225 230 235 240
Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro
245 250 255
Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val
260 265 270
Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr
275 280 285
Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Val Val Ser Val
290 295 300
Leu Thr Val Val His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys
305 310 315 320
Lys Val Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser
325 330 335
Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro
340 345 350
Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val
355 360 365
Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly
370 375 380
Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Met Leu Asp Ser Asp
385 390 395 400
Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp
405 410 415
Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His
420 425 430
Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
435 440 445
<210> 397
<211> 213
<212> PRT
<213> 智人
<400> 397
Met Gln Leu Pro Leu Ala Leu Cys Leu Val Cys Leu Leu Val His Thr
1 5 10 15
Ala Phe Arg Val Val Glu Gly Gln Gly Trp Gln Ala Phe Lys Asn Asp
20 25 30
Ala Thr Glu Ile Ile Pro Glu Leu Gly Glu Tyr Pro Glu Pro Pro Pro
35 40 45
Glu Leu Glu Asn Asn Lys Thr Met Asn Arg Ala Glu Asn Gly Gly Arg
50 55 60
Pro Pro His His Pro Phe Glu Thr Lys Asp Val Ser Glu Tyr Ser Cys
65 70 75 80
Arg Glu Leu His Phe Thr Arg Tyr Val Thr Asp Gly Pro Cys Arg Ser
85 90 95
Ala Lys Pro Val Thr Glu Leu Val Cys Ser Gly Gln Cys Gly Pro Ala
100 105 110
Arg Leu Leu Pro Asn Ala Ile Gly Arg Gly Lys Trp Trp Arg Pro Ser
115 120 125
Gly Pro Asp Phe Arg Cys Ile Pro Asp Arg Tyr Arg Ala Gln Arg Val
130 135 140
Gln Leu Leu Cys Pro Gly Gly Glu Ala Pro Arg Ala Arg Lys Val Arg
145 150 155 160
Leu Val Ala Ser Cys Lys Cys Lys Arg Leu Thr Arg Phe His Asn Gln
165 170 175
Ser Glu Leu Lys Asp Phe Gly Thr Glu Ala Ala Arg Pro Gln Lys Gly
180 185 190
Arg Lys Pro Arg Pro Arg Ala Arg Ser Ala Lys Ala Asn Gln Ala Glu
195 200 205
Leu Glu Asn Ala Tyr
210
<210> 398
<211> 444
<212> PRT
<213> 人工
<220>
<223> 杂项构筑体
<400> 398
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Phe Leu Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Thr Ile Tyr Pro Tyr His Asp Gly Thr Thr Tyr Ser Gln Lys Phe
50 55 60
Lys Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Glu Glu Asp Gly Gln Phe Asp Tyr Trp Gly Gln Gly Thr
100 105 110
Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro
115 120 125
Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly
130 135 140
Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn
145 150 155 160
Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln
165 170 175
Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser
180 185 190
Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser
195 200 205
Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys
210 215 220
Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val Phe Leu
225 230 235 240
Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu
245 250 255
Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln
260 265 270
Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys
275 280 285
Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu
290 295 300
Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys
305 310 315 320
Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys
325 330 335
Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser
340 345 350
Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys
355 360 365
Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln
370 375 380
Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly
385 390 395 400
Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln
405 410 415
Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn
420 425 430
His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly
435 440
<210> 399
<211> 444
<212> PRT
<213> 人工
<220>
<223> 杂项构筑体
<400> 399
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Val Ser Gly Phe Pro Ile Lys Asp Thr
20 25 30
Phe Gln His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Trp Ser Asp Pro Glu Ile Gly Asp Thr Glu Tyr Ala Ser Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Glu Asp Thr Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Thr Gly Asp Thr Thr Tyr Lys Phe Asp Phe Trp Gly Gln Gly Thr
100 105 110
Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro
115 120 125
Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly
130 135 140
Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn
145 150 155 160
Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln
165 170 175
Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser
180 185 190
Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser
195 200 205
Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys
210 215 220
Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val Phe Leu
225 230 235 240
Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu
245 250 255
Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln
260 265 270
Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys
275 280 285
Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu
290 295 300
Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys
305 310 315 320
Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys
325 330 335
Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser
340 345 350
Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys
355 360 365
Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln
370 375 380
Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly
385 390 395 400
Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln
405 410 415
Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn
420 425 430
His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly
435 440
<210> 400
<211> 450
<212> PRT
<213> 人工
<220>
<223> 杂项构筑体
<400> 400
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu
1 5 10 15
Ser Leu Lys Ile Ser Cys Lys Gly Ser Asp Phe Glu Ile Lys Asp Tyr
20 25 30
Tyr Ile His Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Gln Ile Asp Ala Glu Asp Gly Glu Thr Glu Tyr Ala Pro Arg Phe
50 55 60
Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys
85 90 95
Ala Arg Glu Gly Tyr Tyr Tyr Asp Gly Arg Asp Tyr Trp Tyr Phe Asp
100 105 110
Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys
115 120 125
Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu
130 135 140
Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro
145 150 155 160
Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr
165 170 175
Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val
180 185 190
Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn
195 200 205
Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser
210 215 220
Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly
225 230 235 240
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
245 250 255
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln
260 265 270
Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val
275 280 285
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr
290 295 300
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
305 310 315 320
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile
325 330 335
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
340 345 350
Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser
355 360 365
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
370 375 380
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
385 390 395 400
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val
405 410 415
Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met
420 425 430
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
435 440 445
Leu Gly
450
<210> 401
<211> 214
<212> PRT
<213> 人工
<220>
<223> 杂项构筑体
<400> 401
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Ser Ala Ser Gln Gly Ile Gln Trp Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Tyr Thr Ser Ser Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln His Ser Lys Leu Pro Arg
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala
100 105 110
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly
115 120 125
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala
130 135 140
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
180 185 190
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser
195 200 205
Phe Asn Arg Gly Glu Cys
210
<210> 402
<211> 214
<212> PRT
<213> 人工
<220>
<223> 杂项构筑体
<400> 402
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val His Thr Ala
20 25 30
Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Trp Ala Ser Thr Arg Trp Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Ser Asp Tyr Pro Trp
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala
100 105 110
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly
115 120 125
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala
130 135 140
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
180 185 190
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser
195 200 205
Phe Asn Arg Gly Glu Cys
210
<210> 403
<211> 213
<212> PRT
<213> 人工
<220>
<223> 杂项构筑体
<400> 403
Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Ser Ala Ser Ser Ser Val Ser Tyr Ile
20 25 30
His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr
35 40 45
Ser Thr Ser Glu Leu Ala Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser
50 55 60
Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro Glu
65 70 75 80
Asp Phe Ala Val Tyr Tyr Cys Gln Gln Leu Ser His Leu Pro Leu Thr
85 90 95
Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro
100 105 110
Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr
115 120 125
Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys
130 135 140
Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu
145 150 155 160
Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser
165 170 175
Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala
180 185 190
Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe
195 200 205
Asn Arg Gly Glu Cys
210
<210> 404
<211> 1332
<212> DNA
<213> 人工
<220>
<223> 杂项构筑体
<400> 404
caggtgcagc tggtgcagtc tggggctgag gtgaagaagc ctgggtcctc agtgaaggtt 60
tcctgcaagg catctggata cacattcact gactactttc tgaactgggt gcgacaggcc 120
cctggacaag ggcttgagtg gatgggaact atttatcctt accatgatgg tactacctac 180
tctcagaagt tcaagggcag agtcaccatt accgcggaca aatccacgag cacagcctac 240
atggagctga gcagcctgag atctgaggac acggccgtgt attactgtgc gagagaggaa 300
gaggatggtc agttcgacta ctggggccaa ggaaccacgg tcaccgtctc ctcagcctcc 360
accaagggcc catcggtctt cccgctagcg ccctgctcca ggagcacctc cgagagcaca 420
gccgccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac 480
tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctcaggactc 540
tactccctca gcagcgtggt gaccgtgccc tccagcagct tgggcacgaa gacctacacc 600
tgcaacgtag atcacaagcc cagcaacacc aaggtggaca agagagttga gtccaaatat 660
ggtcccccat gcccaccctg cccagcacct gagttcctgg ggggaccatc agtcttcctg 720
ttccccccaa aacccaagga cactctcatg atctcccgga cccctgaggt cacgtgcgtg 780
gtggtggacg tgagccagga agaccccgag gtccagttca actggtacgt ggatggcgtg 840
gaggtgcata atgccaagac aaagccgcgg gaggagcagt tcaacagcac gtaccgtgtg 900
gtcagcgtcc tcaccgtcct gcaccaggac tggctgaacg gcaaggagta caagtgcaag 960
gtctccaaca aaggcctccc gtcctccatc gagaaaacca tctccaaagc caaagggcag 1020
ccccgagagc cacaggtgta caccctgccc ccatcccagg aggagatgac caagaaccag 1080
gtcagcctga cctgcctggt caaaggcttc taccccagcg acatcgccgt ggagtgggaa 1140
agcaatgggc agccggagaa caactacaag accacgcctc ccgtgctgga ctccgacggc 1200
tccttcttcc tctacagcag gctaaccgtg gacaagagca ggtggcagga ggggaatgtc 1260
ttctcatgct ccgtgatgca tgaggctctg cacaaccact acacacagaa gagcctctcc 1320
ctgtctctgg gt 1332
<210> 405
<211> 1332
<212> DNA
<213> 人工
<220>
<223> 杂项构筑体
<400> 405
caggttcagc tggtgcagtc tggggctgag gtgaagaagc ctggggcctc agtgaaggtc 60
tcctgcaagg tttccggctt ccccattaag gacacctttc agcactgggt gcgacaggct 120
cctggaaaag ggcttgagtg gatgggatgg agcgatcctg agatcggtga tactgaatat 180
gcctcgaagt tccagggcag agtcaccatg accgaggaca catctacaga cacagcctac 240
atggagctga gcagcctgag atctgaggac acggccgtgt attactgtgc aacaggcgac 300
accacataca agtttgactt ctgggggcaa gggaccacgg tcaccgtctc ctcagcctcc 360
accaagggcc catcggtctt cccgctagcg ccctgctcca ggagcacctc cgagagcaca 420
gccgccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac 480
tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctcaggactc 540
tactccctca gcagcgtggt gaccgtgccc tccagcagct tgggcacgaa gacctacacc 600
tgcaacgtag atcacaagcc cagcaacacc aaggtggaca agagagttga gtccaaatat 660
ggtcccccat gcccaccctg cccagcacct gagttcctgg ggggaccatc agtcttcctg 720
ttccccccaa aacccaagga cactctcatg atctcccgga cccctgaggt cacgtgcgtg 780
gtggtggacg tgagccagga agaccccgag gtccagttca actggtacgt ggatggcgtg 840
gaggtgcata atgccaagac aaagccgcgg gaggagcagt tcaacagcac gtaccgtgtg 900
gtcagcgtcc tcaccgtcct gcaccaggac tggctgaacg gcaaggagta caagtgcaag 960
gtctccaaca aaggcctccc gtcctccatc gagaaaacca tctccaaagc caaagggcag 1020
ccccgagagc cacaggtgta caccctgccc ccatcccagg aggagatgac caagaaccag 1080
gtcagcctga cctgcctggt caaaggcttc taccccagcg acatcgccgt ggagtgggaa 1140
agcaatgggc agccggagaa caactacaag accacgcctc ccgtgctgga ctccgacggc 1200
tccttcttcc tctacagcag gctaaccgtg gacaagagca ggtggcagga ggggaatgtc 1260
ttctcatgct ccgtgatgca tgaggctctg cacaaccact acacacagaa gagcctctcc 1320
ctgtctctgg gt 1332
<210> 406
<211> 1350
<212> DNA
<213> 人工
<220>
<223> 杂项构筑体
<400> 406
gaggtgcagc tggtgcagtc tggagcagag gtgaaaaagc ccggggagtc tctgaagatc 60
tcctgtaagg gttctgactt cgagattaaa gactactata tacattgggt gcgccagatg 120
cccgggaaag gcctggagtg gatggggcag attgatgctg aggatggtga aactgaatat 180
gccccgaggt tccagggcca ggtcaccatc tcagccgaca agtccatcag caccgcctac 240
ctgcagtgga gcagcctgaa ggcctcggac accgccatgt attactgtgc gagagagggt 300
tattactacg atgggcgcga ctactggtac ttcgatgtct ggggccaagg gaccacggtc 360
accgtctcct cagcctccac caagggccca tcggtcttcc cgctagcgcc ctgctccagg 420
agcacctccg agagcacagc cgccctgggc tgcctggtca aggactactt ccccgaaccg 480
gtgacggtgt cgtggaactc aggcgccctg accagcggcg tgcacacctt cccggctgtc 540
ctacagtcct caggactcta ctccctcagc agcgtggtga ccgtgccctc cagcagcttg 600
ggcacgaaga cctacacctg caacgtagat cacaagccca gcaacaccaa ggtggacaag 660
agagttgagt ccaaatatgg tcccccatgc ccaccctgcc cagcacctga gttcctgggg 720
ggaccatcag tcttcctgtt ccccccaaaa cccaaggaca ctctcatgat ctcccggacc 780
cctgaggtca cgtgcgtggt ggtggacgtg agccaggaag accccgaggt ccagttcaac 840
tggtacgtgg atggcgtgga ggtgcataat gccaagacaa agccgcggga ggagcagttc 900
aacagcacgt accgtgtggt cagcgtcctc accgtcctgc accaggactg gctgaacggc 960
aaggagtaca agtgcaaggt ctccaacaaa ggcctcccgt cctccatcga gaaaaccatc 1020
tccaaagcca aagggcagcc ccgagagcca caggtgtaca ccctgccccc atcccaggag 1080
gagatgacca agaaccaggt cagcctgacc tgcctggtca aaggcttcta ccccagcgac 1140
atcgccgtgg agtgggaaag caatgggcag ccggagaaca actacaagac cacgcctccc 1200
gtgctggact ccgacggctc cttcttcctc tacagcaggc taaccgtgga caagagcagg 1260
tggcaggagg ggaatgtctt ctcatgctcc gtgatgcatg aggctctgca caaccactac 1320
acacagaaga gcctctccct gtctctgggt 1350
<210> 407
<211> 642
<212> DNA
<213> 人工
<220>
<223> 杂项构筑体
<400> 407
gacatccaga tgacccagtc tccatcctct ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgca gtgcaagtca gggcattcag tggtatttaa actggtatca gcagaaacca 120
gggaaagccc ctaagctcct gatctattac acatcaagtt tacactcagg ggtcccatca 180
aggttcagtg gcagtggatc tgggacagat ttcactctca ccatcagcag tctgcaacct 240
gaagattttg caacttacta ctgtcagcag catagtaaac ttcctcggac gttcggcgga 300
gggaccaagg tggagatcaa acggactgtg gctgcaccat ctgtcttcat cttcccgcca 360
tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 420
cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 480
gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 540
ctgagcaaag cagactacga gaaacacaaa gtctacgcct gcgaagtcac ccatcagggc 600
ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gc 642
<210> 408
<211> 642
<212> DNA
<213> 人工
<220>
<223> 杂项构筑体
<400> 408
gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgca aggccagtca ggatgtgcac actgctgtag cctggtatca gcagaaacca 120
gggaaagccc ctaagctcct gatctattgg gcatccaccc ggtggactgg agtcccatca 180
aggttcagtg gcagtggatc tgggacagat ttcactctca ccatcagcag tctgcaacct 240
gaagattttg caacttacta ctgtcagcaa tatagcgatt atccgtggac gttcggcgga 300
gggaccaagg tggagatcaa acggactgtg gctgcaccat ctgtcttcat cttcccgcca 360
tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 420
cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 480
gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 540
ctgagcaaag cagactacga gaaacacaaa gtctacgcct gcgaagtcac ccatcagggc 600
ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gc 642
<210> 409
<211> 639
<212> DNA
<213> 人工
<220>
<223> 杂项构筑体
<400> 409
gaaattgtgt tgacacagtc tccagccacc ctgtctttgt ctccagggga aagagccacc 60
ctctcctgca gtgccagctc aagtgtaagt tacatccact ggtaccaaca gaaacctggc 120
caggctccca ggctcctcat ctatagcaca tccgagctgg cttctggcat cccagccagg 180
ttcagtggca gtgggtctgg gacagacttc actctcacca tcagcagcct agagcctgaa 240
gattttgcag tttattactg tcagcagctt agtcatctcc cgctcacgtt cggcggaggg 300
accaaggtgg agatcaaacg aactgtggct gcaccatctg tcttcatctt cccgccatct 360
gatgagcagt tgaaatctgg aactgcctct gttgtgtgcc tgctgaataa cttctatccc 420
agagaggcca aagtacagtg gaaggtggat aacgccctcc aatcgggtaa ctcccaggag 480
agtgtcacag agcaggacag caaggacagc acctacagcc tcagcagcac cctgacgctg 540
agcaaagcag actacgagaa acacaaagtc tacgcctgcg aagtcaccca tcagggcctg 600
agctcgcccg tcacaaagag cttcaacagg ggagagtgc 639
<210> 410
<211> 118
<212> PRT
<213> 人工
<220>
<223> 杂项构筑体
<400> 410
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Phe Leu Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Thr Ile Tyr Pro Tyr His Asp Gly Thr Thr Tyr Ser Gln Lys Phe
50 55 60
Lys Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Glu Glu Asp Gly Gln Phe Asp Tyr Trp Gly Gln Gly Thr
100 105 110
Thr Val Thr Val Ser Ser
115
<210> 411
<211> 118
<212> PRT
<213> 人工
<220>
<223> 杂项构筑体
<400> 411
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Val Ser Gly Phe Pro Ile Lys Asp Thr
20 25 30
Phe Gln His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Trp Ser Asp Pro Glu Ile Gly Asp Thr Glu Tyr Ala Ser Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Glu Asp Thr Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Thr Gly Asp Thr Thr Tyr Lys Phe Asp Phe Trp Gly Gln Gly Thr
100 105 110
Thr Val Thr Val Ser Ser
115
<210> 412
<211> 124
<212> PRT
<213> 人工
<220>
<223> 杂项构筑体
<400> 412
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu
1 5 10 15
Ser Leu Lys Ile Ser Cys Lys Gly Ser Asp Phe Glu Ile Lys Asp Tyr
20 25 30
Tyr Ile His Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Gln Ile Asp Ala Glu Asp Gly Glu Thr Glu Tyr Ala Pro Arg Phe
50 55 60
Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys
85 90 95
Ala Arg Glu Gly Tyr Tyr Tyr Asp Gly Arg Asp Tyr Trp Tyr Phe Asp
100 105 110
Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 413
<211> 107
<212> PRT
<213> 人工
<220>
<223> 杂项构筑体
<400> 413
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Ser Ala Ser Gln Gly Ile Gln Trp Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Tyr Thr Ser Ser Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln His Ser Lys Leu Pro Arg
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105
<210> 414
<211> 107
<212> PRT
<213> 人工
<220>
<223> 杂项构筑体
<400> 414
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val His Thr Ala
20 25 30
Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Trp Ala Ser Thr Arg Trp Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Ser Asp Tyr Pro Trp
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105
<210> 415
<211> 106
<212> PRT
<213> 人工
<220>
<223> 杂项构筑体
<400> 415
Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Ser Ala Ser Ser Ser Val Ser Tyr Ile
20 25 30
His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr
35 40 45
Ser Thr Ser Glu Leu Ala Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser
50 55 60
Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro Glu
65 70 75 80
Asp Phe Ala Val Tyr Tyr Cys Gln Gln Leu Ser His Leu Pro Leu Thr
85 90 95
Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105
<210> 416
<211> 10
<212> PRT
<213> 人工
<220>
<223> 杂项构筑体
<400> 416
Gly Tyr Thr Phe Thr Asp Tyr Phe Leu Asn
1 5 10
<210> 417
<211> 17
<212> PRT
<213> 人工
<220>
<223> 杂项构筑体
<400> 417
Thr Ile Tyr Pro Tyr His Asp Gly Thr Thr Tyr Ser Gln Lys Phe Lys
1 5 10 15
Gly
<210> 418
<211> 9
<212> PRT
<213> 人工
<220>
<223> 杂项构筑体
<400> 418
Glu Glu Glu Asp Gly Gln Phe Asp Tyr
1 5
<210> 419
<211> 11
<212> PRT
<213> 人工
<220>
<223> 杂项构筑体
<400> 419
Ser Ala Ser Gln Gly Ile Gln Trp Tyr Leu Asn
1 5 10
<210> 420
<211> 7
<212> PRT
<213> 人工
<220>
<223> 杂项构筑体
<400> 420
Tyr Thr Ser Ser Leu His Ser
1 5
<210> 421
<211> 9
<212> PRT
<213> 人工
<220>
<223> 杂项构筑体
<400> 421
Gln Gln His Ser Lys Leu Pro Arg Thr
1 5
<210> 422
<211> 10
<212> PRT
<213> 人工
<220>
<223> 杂项构筑体
<400> 422
Gly Phe Pro Ile Lys Asp Thr Phe Gln His
1 5 10
<210> 423
<211> 17
<212> PRT
<213> 人工
<220>
<223> 杂项构筑体
<400> 423
Trp Ser Asp Pro Glu Ile Gly Asp Thr Glu Tyr Ala Ser Lys Phe Gln
1 5 10 15
Gly
<210> 424
<211> 9
<212> PRT
<213> 人工
<220>
<223> 杂项构筑体
<400> 424
Gly Asp Thr Thr Tyr Lys Phe Asp Phe
1 5
<210> 425
<211> 11
<212> PRT
<213> 人工
<220>
<223> 杂项构筑体
<400> 425
Lys Ala Ser Gln Asp Val His Thr Ala Val Ala
1 5 10
<210> 426
<211> 7
<212> PRT
<213> 人工
<220>
<223> 杂项构筑体
<400> 426
Trp Ala Ser Thr Arg Trp Thr
1 5
<210> 427
<211> 9
<212> PRT
<213> 人工
<220>
<223> 杂项构筑体
<400> 427
Gln Gln Tyr Ser Asp Tyr Pro Trp Thr
1 5
<210> 428
<211> 10
<212> PRT
<213> 人工
<220>
<223> 杂项构筑体
<400> 428
Asp Phe Glu Ile Lys Asp Tyr Tyr Ile His
1 5 10
<210> 429
<211> 17
<212> PRT
<213> 人工
<220>
<223> 杂项构筑体
<400> 429
Gln Ile Asp Ala Glu Asp Gly Glu Thr Glu Tyr Ala Pro Arg Phe Gln
1 5 10 15
Gly
<210> 430
<211> 17
<212> PRT
<213> 人工
<220>
<223> 杂项构筑体
<400> 430
Gln Ile Asp Ala Glu Asp Gly Glu Thr Glu Tyr Ala Pro Arg Phe Gln
1 5 10 15
Gly
<210> 431
<211> 17
<212> PRT
<213> 人工
<220>
<223> 杂项构筑体
<400> 431
Gln Ile Asp Ala Glu Asp Gly Glu Thr Glu Tyr Ala Pro Arg Phe Gln
1 5 10 15
Gly
<210> 432
<211> 7
<212> PRT
<213> 人工
<220>
<223> 杂项构筑体
<400> 432
Ser Thr Ser Glu Leu Ala Ser
1 5
<210> 433
<211> 9
<212> PRT
<213> 人工
<220>
<223> 杂项构筑体
<400> 433
Gln Gln Leu Ser His Leu Pro Leu Thr
1 5
<210> 434
<211> 322
<212> PRT
<213> 人工
<220>
<223> 杂项构筑体
<400> 434
Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu
1 5 10 15
Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro
20 25 30
Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr
35 40 45
Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val
50 55 60
Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn
65 70 75 80
Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser
85 90 95
Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly
100 105 110
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
115 120 125
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln
130 135 140
Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val
145 150 155 160
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr
165 170 175
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
180 185 190
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile
195 200 205
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
210 215 220
Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser
225 230 235 240
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
245 250 255
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
260 265 270
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val
275 280 285
Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met
290 295 300
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
305 310 315 320
Leu Gly
<210> 435
<211> 970
<212> DNA
<213> 人工
<220>
<223> 杂项构筑体
<400> 435
ggcccatcgg tcttcccgct agcgccctgc tccaggagca cctccgagag cacagccgcc 60
ctgggctgcc tggtcaagga ctacttcccc gaaccggtga cggtgtcgtg gaactcaggc 120
gccctgacca gcggcgtgca caccttcccg gctgtcctac agtcctcagg actctactcc 180
gctcagcagc gtggtgaccg tgccctccag cagcttgggc acgaagacct acacctgcaa 240
cgtagatcac aagcccagca acaccaaggt ggacaagaga gttgagtcca aatatggtcc 300
cccatgccca ccctgcccag cacctgagtt cctgggggga ccatcagtct tcctgttccc 360
cccaaaaccc aaggacactc tcatgatctc ccggacccct gaggtcacgt gcgtggtggt 420
ggacgtgagc caggaagacc ccgaggtcca gttcaactgg tacgtggatg gcgtggaggt 480
gcataatgcc aagacaaagc cgcgggagga gcagttcaac agcacgtacc gtgtggtcag 540
cgtcctcacc gtcctgcacc aggactggct gaacggcaag gagtacaagt gcaaggtctc 600
caacaaaggc ctcccgtcct ccatcgagaa aaccatctcc aaagccaaag ggcagccccg 660
agagccacag gtgtacaccc tgcccccatc ccaggaggag atgaccaaga accaggtcag 720
cctgacctgc ctggtcaaag gcttctaccc cagcgacatc gccgtggagt gggaaagcaa 780
tgggcagccg gagaacaact acaagaccac gcctcccgtg ctggactccg acggctcctt 840
cttcctctac agcaggctaa ccgtggacaa gagcaggtgg caggagggga atgtcttctc 900
atgctccgtg atgcatgagg ctctgcacaa ccactacaca cagaagagcc tctccctgtc 960
tctgggttga 970
<210> 436
<211> 444
<212> PRT
<213> 人工
<220>
<223> 杂项构筑体
<400> 436
Glu Val Gln Leu Gln Gln Ser Val Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Lys Leu Ser Cys Thr Ala Ser Gly Phe Asn Ile Lys Ser Thr
20 25 30
Phe Met His Trp Val Lys Gln Arg Pro Asp Gln Gly Leu Glu Trp Ile
35 40 45
Gly Trp Ile Asp Pro Glu Asn Gly Asp Thr Glu Tyr Ala Ser Lys Phe
50 55 60
Gln Gly Lys Ala Thr Met Thr Ala Asp Thr Ser Ser Asn Thr Ala Tyr
65 70 75 80
Leu Gln Leu Ser Ser Leu Thr Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Thr Gly Glu Ser Asn Tyr Asp Phe Asp Phe Trp Gly Leu Gly Thr
100 105 110
Thr Leu Thr Val Ser Ser Ala Lys Thr Thr Pro Pro Ser Val Tyr Pro
115 120 125
Leu Ala Pro Gly Thr Ala Leu Lys Ser Asn Ser Met Val Thr Leu Gly
130 135 140
Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val Thr Val Thr Trp Asn
145 150 155 160
Ser Gly Ala Leu Ser Ser Gly Val His Thr Phe Pro Ala Val Leu Gln
165 170 175
Ser Gly Leu Tyr Thr Leu Thr Ser Ser Val Thr Val Pro Ser Ser Thr
180 185 190
Trp Pro Ser Gln Thr Val Thr Cys Asn Val Ala His Pro Ala Ser Ser
195 200 205
Thr Lys Val Asp Lys Lys Ile Val Pro Arg Asn Cys Gly Gly Asp Cys
210 215 220
Lys Pro Cys Ile Cys Thr Gly Ser Glu Val Ser Ser Val Phe Ile Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro Lys Val
245 250 255
Thr Cys Val Val Val Asp Ile Ser Gln Asp Asp Pro Glu Val His Phe
260 265 270
Ser Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr Arg Pro
275 280 285
Pro Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser Glu Leu Pro
290 295 300
Ile Leu His Gln Asp Trp Leu Asn Gly Arg Thr Phe Arg Cys Lys Val
305 310 315 320
Thr Ser Ala Ala Phe Pro Ser Pro Ile Glu Lys Thr Ile Ser Lys Pro
325 330 335
Glu Gly Arg Thr Gln Val Pro His Val Tyr Thr Met Ser Pro Thr Lys
340 345 350
Glu Glu Met Thr Gln Asn Glu Val Ser Ile Thr Cys Met Val Lys Gly
355 360 365
Phe Tyr Pro Pro Asp Ile Tyr Val Glu Trp Gln Met Asn Gly Gln Pro
370 375 380
Gln Glu Asn Tyr Lys Asn Thr Pro Pro Thr Met Asp Thr Asp Gly Ser
385 390 395 400
Tyr Phe Leu Tyr Ser Lys Leu Asn Val Lys Lys Glu Lys Trp Gln Gln
405 410 415
Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His Asn His
420 425 430
His Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys
435 440
<210> 437
<211> 214
<212> PRT
<213> 人工
<220>
<223> 杂项构筑体
<400> 437
Asp Ile Val Met Thr Gln Ser His Lys Phe Met Ser Thr Ser Val Gly
1 5 10 15
Asp Arg Val Ser Ile Thr Cys Lys Ala Ser Gln Asp Val Ser Thr Ala
20 25 30
Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile
35 40 45
Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Asp Arg Phe Thr Gly
50 55 60
Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Asp Val Gln Ser
65 70 75 80
Glu Asp Leu Ala Asp Tyr Phe Cys Gln Gln Tyr Ser Asn Tyr Pro Trp
85 90 95
Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Ala Asp Ala Ala
100 105 110
Pro Thr Val Ser Ile Phe Pro Pro Ser Thr Glu Gln Leu Ala Thr Gly
115 120 125
Gly Ala Ser Val Val Cys Leu Met Asn Asn Phe Tyr Pro Arg Asp Ile
130 135 140
Ser Val Lys Trp Lys Ile Asp Gly Thr Glu Arg Arg Asp Gly Val Leu
145 150 155 160
Asp Ser Val Thr Asp Gln Asp Ser Lys Asp Ser Thr Tyr Ser Met Ser
165 170 175
Ser Thr Leu Ser Leu Ser Lys Ala Asp Tyr Glu Ser His Asn Leu Tyr
180 185 190
Thr Cys Glu Val Val His Lys Thr Ser Ser Ser Pro Val Val Lys Ser
195 200 205
Phe Asn Arg Asn Glu Cys
210
<210> 438
<211> 450
<212> PRT
<213> 人工
<220>
<223> 杂项构筑体
<400> 438
Glu Val Gln Leu Gln Gln Ser Gly Ala Glu His Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Leu Ser Cys Thr Ala Ser Asp Phe Asn Ile Lys Asp Tyr
20 25 30
Tyr Ile His Trp Val Lys Gln Arg Thr Ala Gln Gly Leu Glu Trp Ile
35 40 45
Gly Arg Ile Asp Pro Glu Asp Gly Glu Thr Glu Tyr Ala Pro Arg Phe
50 55 60
Gln Gly Lys Ala Thr Ile Ile Ala Asp Thr Ser Ser Asn Thr Ala Tyr
65 70 75 80
Leu Gln Leu Ser Ser Leu Thr Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Gly Tyr Tyr Tyr Asp Ser Arg Asp Tyr Trp Tyr Phe Asp
100 105 110
Val Trp Gly Thr Gly Thr Thr Val Thr Val Ser Ser Ala Lys Thr Thr
115 120 125
Pro Pro Ser Val Tyr Pro Leu Ala Pro Gly Thr Ala Leu Lys Ser Asn
130 135 140
Ser Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro
145 150 155 160
Val Thr Val Thr Trp Asn Ser Gly Ala Leu Ser Ser Gly Val His Thr
165 170 175
Phe Pro Ala Val Leu Gln Ser Gly Leu Tyr Thr Leu Thr Ser Ser Val
180 185 190
Thr Val Pro Ser Ser Thr Trp Pro Ser Gln Thr Val Thr Cys Asn Val
195 200 205
Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val Pro Arg
210 215 220
Asn Cys Gly Gly Asp Cys Lys Pro Cys Ile Cys Thr Gly Ser Glu Val
225 230 235 240
Ser Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile
245 250 255
Thr Leu Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Gln Asp
260 265 270
Asp Pro Glu Val His Phe Ser Trp Phe Val Asp Asp Val Glu Val His
275 280 285
Thr Ala Gln Thr Arg Pro Pro Glu Glu Gln Phe Asn Ser Thr Phe Arg
290 295 300
Ser Val Ser Glu Leu Pro Ile Leu His Gln Asp Trp Leu Asn Gly Arg
305 310 315 320
Thr Phe Arg Cys Lys Val Thr Ser Ala Ala Phe Pro Ser Pro Ile Glu
325 330 335
Lys Thr Ile Ser Lys Pro Glu Gly Arg Thr Gln Val Pro His Val Tyr
340 345 350
Thr Met Ser Pro Thr Lys Glu Glu Met Thr Gln Asn Glu Val Ser Ile
355 360 365
Thr Cys Met Val Lys Gly Phe Tyr Pro Pro Asp Ile Tyr Val Glu Trp
370 375 380
Gln Met Asn Gly Gln Pro Gln Glu Asn Tyr Lys Asn Thr Pro Pro Thr
385 390 395 400
Met Asp Thr Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Asn Val Lys
405 410 415
Lys Glu Lys Trp Gln Gln Gly Asn Thr Phe Thr Cys Ser Val Leu His
420 425 430
Glu Gly Leu His Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro
435 440 445
Gly Lys
450
<210> 439
<211> 213
<212> PRT
<213> 人工
<220>
<223> 杂项构筑体
<400> 439
Glu Ile Val Leu Thr Gln Ser Pro Ala Leu Met Ser Ala Ser Pro Gly
1 5 10 15
Glu Lys Val Thr Met Thr Cys Ser Ala Ser Ser Ser Val Ser Tyr Met
20 25 30
His Trp Phe Gln Gln Lys Pro Gly Thr Ser Pro Lys Leu Trp Ile Tyr
35 40 45
Ser Thr Ser Asn Leu Ala Ser Gly Val Pro Ala Arg Phe Ser Gly Ser
50 55 60
Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile Ser Ser Met Glu Ala Glu
65 70 75 80
Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Trp Ser Ser Asn Pro Leu Thr
85 90 95
Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys Arg Ala Asp Ala Ala Pro
100 105 110
Thr Val Ser Ile Phe Pro Pro Ser Thr Glu Gln Leu Ala Thr Gly Gly
115 120 125
Ala Ser Val Val Cys Leu Met Asn Asn Phe Tyr Pro Arg Asp Ile Ser
130 135 140
Val Lys Trp Lys Ile Asp Gly Thr Glu Arg Arg Asp Gly Val Leu Asp
145 150 155 160
Ser Val Thr Asp Gln Asp Ser Lys Asp Ser Thr Tyr Ser Met Ser Ser
165 170 175
Thr Leu Ser Leu Ser Lys Ala Asp Tyr Glu Ser His Asn Leu Tyr Thr
180 185 190
Cys Glu Val Val His Lys Thr Ser Ser Ser Pro Val Val Lys Ser Phe
195 200 205
Asn Arg Asn Glu Cys
210
<210> 440
<211> 10
<212> PRT
<213> 智人
<400> 440
Gly Phe Thr Phe Ser Ser Tyr Val Met Asn
1 5 10
<210> 441
<211> 10
<212> PRT
<213> 智人
<400> 441
Gly Phe Thr Phe Arg Ser His Trp Leu Ser
1 5 10
<210> 442
<211> 10
<212> PRT
<213> 智人
<400> 442
Gly Phe Thr Phe Ser Ser Tyr Val Met Asn
1 5 10
<210> 443
<211> 10
<212> PRT
<213> 智人
<400> 443
Gly Phe Thr Phe Arg Ser His Trp Leu Ser
1 5 10
<210> 444
<211> 10
<212> PRT
<213> 智人
<400> 444
Gly Phe Thr Phe Arg Ser His Trp Leu Ser
1 5 10
<210> 445
<211> 10
<212> PRT
<213> 智人
<400> 445
Gly Phe Thr Phe Arg Ser His Trp Leu Ser
1 5 10
<210> 446
<211> 10
<212> PRT
<213> 智人
<400> 446
Gly Phe Thr Phe Arg Ser His Trp Leu Ser
1 5 10
<210> 447
<211> 10
<212> PRT
<213> 智人
<400> 447
Gly Phe Thr Phe Arg Ser His Trp Leu Ser
1 5 10
<210> 448
<211> 10
<212> PRT
<213> 智人
<400> 448
Gly Phe Thr Phe Arg Ser His Trp Leu Ser
1 5 10
<210> 449
<211> 10
<212> PRT
<213> 智人
<400> 449
Gly Phe Thr Phe Arg Ser His Trp Leu Ser
1 5 10
<210> 450
<211> 10
<212> PRT
<213> 智人
<400> 450
Gly Phe Thr Phe Arg Ser His Trp Leu Ser
1 5 10
<210> 451
<211> 20
<212> PRT
<213> 智人
<400> 451
Trp Val Ser Phe Ile Ser Gly Asp Ser Ser Asn Thr Tyr Tyr Ala Asp
1 5 10 15
Ser Val Lys Gly
20
<210> 452
<211> 20
<212> PRT
<213> 智人
<400> 452
Trp Val Ser Asn Ile Asn Tyr Asp Gly Ser Ser Thr Tyr Tyr Ala Asp
1 5 10 15
Ser Val Lys Gly
20
<210> 453
<211> 20
<212> PRT
<213> 智人
<400> 453
Trp Val Ser Phe Ile Ser Gly Asp Ser Ser Asn Thr Tyr Tyr Ala Asp
1 5 10 15
Ser Val Lys Gly
20
<210> 454
<211> 20
<212> PRT
<213> 智人
<400> 454
Trp Val Ser Asn Ile Asn Tyr Asp Gly Ser Ser Thr Tyr Tyr Ala Asp
1 5 10 15
Ser Val Lys Gly
20
<210> 455
<211> 19
<212> PRT
<213> 智人
<400> 455
Trp Val Ser Val Thr Gly Val His Gly Asp Thr Tyr Tyr Ala Asp Ser
1 5 10 15
Val Lys Gly
<210> 456
<211> 19
<212> PRT
<213> 智人
<400> 456
Trp Val Ser Val Ile Gly Asn Trp Gly Asp Thr Tyr Tyr Ala Asp Ser
1 5 10 15
Val Lys Gly
<210> 457
<211> 19
<212> PRT
<213> 智人
<400> 457
Trp Val Ser Val Thr Thr His Gln Gly Tyr Thr Tyr Tyr Ala Asp Ser
1 5 10 15
Val Lys Gly
<210> 458
<211> 19
<212> PRT
<213> 智人
<400> 458
Trp Val Ser Ala Thr Asn Arg Tyr Gly Tyr Thr Tyr Tyr Ala Asp Ser
1 5 10 15
Val Lys Gly
<210> 459
<211> 20
<212> PRT
<213> 智人
<400> 459
Trp Val Ser Asn Ile Asn Tyr Asp Gly Ser Ser Thr Tyr Tyr Ala Asp
1 5 10 15
Ser Val Lys Gly
20
<210> 460
<211> 19
<212> PRT
<213> 智人
<400> 460
Trp Val Ser Val Ile Thr Pro Tyr Gly Asp Thr Tyr Tyr Ala Asp Ser
1 5 10 15
Val Lys Gly
<210> 461
<211> 19
<212> PRT
<213> 智人
<400> 461
Trp Val Ser Val Ile Thr Pro Tyr Gly Asp Thr Tyr Tyr Ala Asp Ser
1 5 10 15
Val Lys Gly
<210> 462
<211> 15
<212> PRT
<213> 智人
<400> 462
Thr Phe Met His Gly His Leu Gly Gly Gly Leu Ser Met Asp Phe
1 5 10 15
<210> 463
<211> 8
<212> PRT
<213> 智人
<400> 463
Asp Thr Tyr Leu His Phe Asp Tyr
1 5
<210> 464
<211> 15
<212> PRT
<213> 智人
<400> 464
Thr Phe Met His Gly His Leu Gly Gly Gly Leu Ser Met Asp Phe
1 5 10 15
<210> 465
<211> 8
<212> PRT
<213> 智人
<400> 465
Asp Thr Tyr Leu His Phe Asp Tyr
1 5
<210> 466
<211> 8
<212> PRT
<213> 智人
<400> 466
Asp Thr Tyr Leu His Phe Asp Tyr
1 5
<210> 467
<211> 8
<212> PRT
<213> 智人
<400> 467
Asp Thr Tyr Leu His Phe Asp Tyr
1 5
<210> 468
<211> 8
<212> PRT
<213> 智人
<400> 468
Asp Thr Tyr Leu His Phe Asp Tyr
1 5
<210> 469
<211> 8
<212> PRT
<213> 智人
<400> 469
Asp Thr Tyr Leu His Phe Asp Tyr
1 5
<210> 470
<211> 8
<212> PRT
<213> 智人
<400> 470
Asp Thr Tyr Leu His Phe Asp Tyr
1 5
<210> 471
<211> 8
<212> PRT
<213> 智人
<400> 471
Asp Thr Tyr Leu His Phe Asp Tyr
1 5
<210> 472
<211> 8
<212> PRT
<213> 智人
<400> 472
Asp Thr Tyr Leu His Phe Asp Tyr
1 5
<210> 473
<211> 11
<212> PRT
<213> 智人
<400> 473
Ser Gly Asp Asn Ile Gly Ser Phe Tyr Val His
1 5 10
<210> 474
<211> 20
<212> PRT
<213> 智人
<400> 474
Trp Val Ser Asn Ile Asn Tyr Asp Gly Ser Ser Thr Tyr Tyr Ala Asp
1 5 10 15
Ser Val Lys Gly
20
<210> 475
<211> 20
<212> PRT
<213> 智人
<400> 475
Trp Val Ser Asn Ile Asn Tyr Asp Gly Ser Ser Thr Tyr Tyr Ala Asp
1 5 10 15
Ser Val Lys Gly
20
<210> 476
<211> 11
<212> PRT
<213> 智人
<400> 476
Ser Gly Asp Asn Ile Gly Ser Phe Tyr Val His
1 5 10
<210> 477
<211> 14
<212> PRT
<213> 智人
<400> 477
Thr Gly Thr Ser Ser Asp Val Gly Asp Ile Asn Asp Val Ser
1 5 10
<210> 478
<211> 14
<212> PRT
<213> 智人
<400> 478
Thr Gly Thr Ser Ser Asp Val Gly Asp Ile Asn Asp Val Ser
1 5 10
<210> 479
<211> 14
<212> PRT
<213> 智人
<400> 479
Thr Gly Thr Ser Ser Asp Val Gly Asp Ile Asn Asp Val Ser
1 5 10
<210> 480
<211> 14
<212> PRT
<213> 智人
<400> 480
Thr Gly Thr Ser Ser Asp Val Gly Asp Ile Asn Asp Val Ser
1 5 10
<210> 481
<211> 14
<212> PRT
<213> 智人
<400> 481
Thr Gly Thr Ser Ser Asp Val Gly Asp Ile Asn Asp Val Ser
1 5 10
<210> 482
<211> 14
<212> PRT
<213> 智人
<400> 482
Thr Gly Thr Ser Ser Asp Val Gly Asp Ile Asn Asp Val Ser
1 5 10
<210> 483
<211> 14
<212> PRT
<213> 智人
<400> 483
Thr Gly Thr Ser Ser Asp Val Gly Asp Ile Asn Asp Val Ser
1 5 10
<210> 484
<211> 11
<212> PRT
<213> 智人
<400> 484
Leu Val Ile Tyr Asp Asp Asn Asn Arg Pro Ser
1 5 10
<210> 485
<211> 11
<212> PRT
<213> 智人
<400> 485
Leu Met Ile Tyr Asp Val Asn Asn Arg Pro Ser
1 5 10
<210> 486
<211> 11
<212> PRT
<213> 智人
<400> 486
Leu Val Ile Tyr Asp Asp Asn Asn Arg Pro Ser
1 5 10
<210> 487
<211> 11
<212> PRT
<213> 智人
<400> 487
Leu Met Ile Tyr Asp Val Asn Asn Arg Pro Ser
1 5 10
<210> 488
<211> 11
<212> PRT
<213> 智人
<400> 488
Leu Met Ile Tyr Asp Val Asn Asn Arg Pro Ser
1 5 10
<210> 489
<211> 11
<212> PRT
<213> 智人
<400> 489
Leu Met Ile Tyr Asp Val Asn Asn Arg Pro Ser
1 5 10
<210> 490
<211> 11
<212> PRT
<213> 智人
<400> 490
Leu Met Ile Tyr Asp Val Asn Asn Arg Pro Ser
1 5 10
<210> 491
<211> 11
<212> PRT
<213> 智人
<400> 491
Leu Met Ile Tyr Asp Val Asn Asn Arg Pro Ser
1 5 10
<210> 492
<211> 11
<212> PRT
<213> 智人
<400> 492
Leu Met Ile Tyr Asp Val Asn Asn Arg Pro Ser
1 5 10
<210> 493
<211> 11
<212> PRT
<213> 智人
<400> 493
Leu Met Ile Tyr Asp Val Asn Asn Arg Pro Ser
1 5 10
<210> 494
<211> 11
<212> PRT
<213> 智人
<400> 494
Leu Met Ile Tyr Asp Val Asn Asn Arg Pro Ser
1 5 10
<210> 495
<211> 10
<212> PRT
<213> 智人
<400> 495
Gly Ser Trp Ala Gly Ser Ser Gly Ser Tyr
1 5 10
<210> 496
<211> 10
<212> PRT
<213> 智人
<400> 496
Ser Ser Tyr Gly Glu Ser Leu Thr Ser Tyr
1 5 10
<210> 497
<211> 10
<212> PRT
<213> 智人
<400> 497
Ala Ser Trp Thr Gly Val Glu Pro Asp Tyr
1 5 10
<210> 498
<211> 10
<212> PRT
<213> 智人
<400> 498
Gln Ser Tyr Ala Gly Ser Tyr Leu Ser Glu
1 5 10
<210> 499
<211> 10
<212> PRT
<213> 智人
<400> 499
Ser Ser Tyr Gly Glu Ser Leu Thr Ser Tyr
1 5 10
<210> 500
<211> 10
<212> PRT
<213> 智人
<400> 500
Ser Ser Tyr Gly Glu Ser Leu Thr Ser Tyr
1 5 10
<210> 501
<211> 10
<212> PRT
<213> 智人
<400> 501
Ser Ser Tyr Gly Glu Ser Leu Thr Ser Tyr
1 5 10
<210> 502
<211> 10
<212> PRT
<213> 智人
<400> 502
Ser Ser Tyr Gly Glu Ser Leu Thr Ser Tyr
1 5 10
<210> 503
<211> 10
<212> PRT
<213> 智人
<400> 503
Ser Thr Tyr Asp Gly Pro Gly Leu Ser Glu
1 5 10
<210> 504
<211> 10
<212> PRT
<213> 智人
<400> 504
Ser Ser Tyr Gly Glu Ser Leu Thr Ser Tyr
1 5 10
<210> 505
<211> 10
<212> PRT
<213> 智人
<400> 505
Ser Ser Tyr Gly Glu Ser Leu Thr Ser Tyr
1 5 10
<210> 506
<211> 124
<212> PRT
<213> 智人
<400> 506
Gln 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 Thr Phe Ser Ser Tyr
20 25 30
Val Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Phe Ile Ser Gly Asp Ser Ser Asn Thr Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Thr Phe Met His Gly His Leu Gly Gly Gly Leu Ser Met Asp
100 105 110
Phe Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 507
<211> 117
<212> PRT
<213> 智人
<400> 507
Gln 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 Thr Phe Arg Ser His
20 25 30
Trp Leu Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Asn Ile Asn Tyr Asp Gly Ser Ser Thr Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Thr Tyr Leu His Phe Asp Tyr Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ser
115
<210> 508
<211> 124
<212> PRT
<213> 智人
<400> 508
Gln 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 Thr Phe Ser Ser Tyr
20 25 30
Val Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Phe Ile Ser Gly Asp Ser Ser Asn Thr Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Thr Phe Met His Gly His Leu Gly Gly Gly Leu Ser Met Asp
100 105 110
Phe Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 509
<211> 117
<212> PRT
<213> 智人
<400> 509
Gln 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 Thr Phe Arg Ser His
20 25 30
Trp Leu Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Asn Ile Asn Tyr Asp Gly Ser Ser Thr Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Thr Tyr Leu His Phe Asp Tyr Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ser
115
<210> 510
<211> 116
<212> PRT
<213> 智人
<400> 510
Gln 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 Thr Phe Arg Ser His
20 25 30
Trp Leu Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Val Thr Gly Val His Gly Asp Thr Tyr Tyr Ala Asp Ser Val 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 Ala
85 90 95
Arg Asp Thr Tyr Leu His Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser
115
<210> 511
<211> 116
<212> PRT
<213> 智人
<400> 511
Gln 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 Thr Phe Arg Ser His
20 25 30
Trp Leu Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Val Ile Gly Asn Trp Gly Asp Thr Tyr Tyr Ala Asp Ser Val 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 Ala
85 90 95
Arg Asp Thr Tyr Leu His Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser
115
<210> 512
<211> 116
<212> PRT
<213> 智人
<400> 512
Gln 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 Thr Phe Arg Ser His
20 25 30
Trp Leu Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Val Thr Thr His Gln Gly Tyr Thr Tyr Tyr Ala Asp Ser Val 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 Ala
85 90 95
Arg Asp Thr Tyr Leu His Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser
115
<210> 513
<211> 116
<212> PRT
<213> 智人
<400> 513
Gln 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 Thr Phe Arg Ser His
20 25 30
Trp Leu Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Ala Thr Asn Arg Tyr Gly Tyr Thr Tyr Tyr Ala Asp Ser Val 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 Ala
85 90 95
Arg Asp Thr Tyr Leu His Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser
115
<210> 514
<211> 117
<212> PRT
<213> 智人
<400> 514
Gln 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 Thr Phe Arg Ser His
20 25 30
Trp Leu Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Asn Ile Asn Tyr Asp Gly Ser Ser Thr Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Thr Tyr Leu His Phe Asp Tyr Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ser
115
<210> 515
<211> 116
<212> PRT
<213> 智人
<400> 515
Gln 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 Thr Phe Arg Ser His
20 25 30
Trp Leu Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Val Ile Thr Pro Tyr Gly Asp Thr Tyr Tyr Ala Asp Ser Val 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 Ala
85 90 95
Arg Asp Thr Tyr Leu His Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser
115
<210> 516
<211> 116
<212> PRT
<213> 智人
<400> 516
Gln 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 Thr Phe Arg Ser His
20 25 30
Trp Leu Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Val Ile Thr Pro Tyr Gly Asp Thr Tyr Tyr Ala Asp Ser Val 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 Ala
85 90 95
Arg Asp Thr Tyr Leu His Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser
115
<210> 517
<211> 110
<212> PRT
<213> 智人
<400> 517
Asp Ile Glu Leu Thr Gln Pro Pro Ser Val Ser Val Ala Pro Gly Gln
1 5 10 15
Thr Ala Arg Ile Ser Cys Ser Gly Asp Asn Ile Gly Ser Phe Tyr Val
20 25 30
His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile Tyr
35 40 45
Asp Asp Asn Asn Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser
50 55 60
Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Gly Thr Gln Ala Glu
65 70 75 80
Asp Glu Ala Asp Tyr Tyr Cys Gly Ser Trp Ala Gly Ser Ser Gly Ser
85 90 95
Tyr Val Phe Gly Gly Arg Thr Lys Leu Thr Val Leu Gly Gln
100 105 110
<210> 518
<211> 113
<212> PRT
<213> 智人
<400> 518
Asp Ile Ala Leu Thr Gln Pro Ala Ser Val Ser Gly Ser Pro Gly Gln
1 5 10 15
Ser Ile Thr Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly Asp Ile
20 25 30
Asn Asp Val Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu
35 40 45
Met Ile Tyr Asp Val Asn Asn Arg Pro Ser Gly Val Ser Asn Arg Phe
50 55 60
Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr Ile Ser Gly Leu
65 70 75 80
Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Gly Glu Ser
85 90 95
Leu Thr Ser Tyr Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly
100 105 110
Gln
<210> 519
<211> 110
<212> PRT
<213> 智人
<400> 519
Asp Ile Glu Leu Thr Gln Pro Pro Ser Val Ser Val Ala Pro Gly Gln
1 5 10 15
Thr Ala Arg Ile Ser Cys Ser Gly Asp Asn Ile Gly Ser Phe Tyr Val
20 25 30
His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile Tyr
35 40 45
Asp Asp Asn Asn Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser
50 55 60
Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Gly Thr Gln Ala Glu
65 70 75 80
Asp Glu Ala Asp Tyr Tyr Cys Ala Ser Trp Thr Gly Val Glu Pro Asp
85 90 95
Tyr Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln
100 105 110
<210> 520
<211> 113
<212> PRT
<213> 智人
<400> 520
Asp Ile Ala Leu Thr Gln Pro Ala Ser Val Ser Gly Ser Pro Gly Gln
1 5 10 15
Ser Ile Thr Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly Asp Ile
20 25 30
Asn Asp Val Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu
35 40 45
Met Ile Tyr Asp Val Asn Asn Arg Pro Ser Gly Val Ser Asn Arg Phe
50 55 60
Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr Ile Ser Gly Leu
65 70 75 80
Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Gln Ser Tyr Ala Gly Ser
85 90 95
Tyr Leu Ser Glu Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly
100 105 110
Gln
<210> 521
<211> 113
<212> PRT
<213> 智人
<400> 521
Asp Ile Ala Leu Thr Gln Pro Ala Ser Val Ser Gly Ser Pro Gly Gln
1 5 10 15
Ser Ile Thr Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly Asp Ile
20 25 30
Asn Asp Val Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu
35 40 45
Met Ile Tyr Asp Val Asn Asn Arg Pro Ser Gly Val Ser Asn Arg Phe
50 55 60
Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr Ile Ser Gly Leu
65 70 75 80
Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Gly Glu Ser
85 90 95
Leu Thr Ser Tyr Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly
100 105 110
Gln
<210> 522
<211> 113
<212> PRT
<213> 智人
<400> 522
Asp Ile Ala Leu Thr Gln Pro Ala Ser Val Ser Gly Ser Pro Gly Gln
1 5 10 15
Ser Ile Thr Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly Asp Ile
20 25 30
Asn Asp Val Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu
35 40 45
Met Ile Tyr Asp Val Asn Asn Arg Pro Ser Gly Val Ser Asn Arg Phe
50 55 60
Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr Ile Ser Gly Leu
65 70 75 80
Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Gly Glu Ser
85 90 95
Leu Thr Ser Tyr Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly
100 105 110
Gln
<210> 523
<211> 113
<212> PRT
<213> 智人
<400> 523
Asp Ile Ala Leu Thr Gln Pro Ala Ser Val Ser Gly Ser Pro Gly Gln
1 5 10 15
Ser Ile Thr Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly Asp Ile
20 25 30
Asn Asp Val Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu
35 40 45
Met Ile Tyr Asp Val Asn Asn Arg Pro Ser Gly Val Ser Asn Arg Phe
50 55 60
Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr Ile Ser Gly Leu
65 70 75 80
Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Gly Glu Ser
85 90 95
Leu Thr Ser Tyr Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly
100 105 110
Gln
<210> 524
<211> 113
<212> PRT
<213> 智人
<400> 524
Asp Ile Ala Leu Thr Gln Pro Ala Ser Val Ser Gly Ser Pro Gly Gln
1 5 10 15
Ser Ile Thr Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly Asp Ile
20 25 30
Asn Asp Val Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu
35 40 45
Met Ile Tyr Asp Val Asn Asn Arg Pro Ser Gly Val Ser Asn Arg Phe
50 55 60
Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr Ile Ser Gly Leu
65 70 75 80
Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Gly Glu Ser
85 90 95
Leu Thr Ser Tyr Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly
100 105 110
Gln
<210> 525
<211> 113
<212> PRT
<213> 智人
<400> 525
Asp Ile Ala Leu Thr Gln Pro Ala Ser Val Ser Gly Ser Pro Gly Gln
1 5 10 15
Ser Ile Thr Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly Asp Ile
20 25 30
Asn Asp Val Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu
35 40 45
Met Ile Tyr Asp Val Asn Asn Arg Pro Ser Gly Val Ser Asn Arg Phe
50 55 60
Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr Ile Ser Gly Leu
65 70 75 80
Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Thr Tyr Asp Gly Pro
85 90 95
Gly Leu Ser Glu Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly
100 105 110
Gln
<210> 526
<211> 113
<212> PRT
<213> 智人
<400> 526
Asp Ile Ala Leu Thr Gln Pro Ala Ser Val Ser Gly Ser Pro Gly Gln
1 5 10 15
Ser Ile Thr Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly Asp Ile
20 25 30
Asn Asp Val Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu
35 40 45
Met Ile Tyr Asp Val Asn Asn Arg Pro Ser Gly Val Ser Asn Arg Phe
50 55 60
Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr Ile Ser Gly Leu
65 70 75 80
Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Gly Glu Ser
85 90 95
Leu Thr Ser Tyr Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly
100 105 110
Gln
<210> 527
<211> 113
<212> PRT
<213> 智人
<400> 527
Asp Ile Ala Leu Thr Gln Pro Ala Ser Val Ser Gly Ser Pro Gly Gln
1 5 10 15
Ser Ile Thr Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly Asp Ile
20 25 30
Asn Asp Val Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu
35 40 45
Met Ile Tyr Asp Val Asn Asn Arg Pro Ser Gly Val Ser Asn Arg Phe
50 55 60
Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr Ile Ser Gly Leu
65 70 75 80
Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Thr Tyr Asp Gly Pro
85 90 95
Gly Leu Ser Glu Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly
100 105 110
Gln
<210> 528
<211> 372
<212> DNA
<213> 智人
<400> 528
caggtgcaat tggtggaaag cggcggcggc ctggtgcaac cgggcggcag cctgcgtctg 60
agctgcgcgg cctccggatt taccttttct tcttatgtta tgaattgggt gcgccaagcc 120
cctgggaagg gtctcgagtg ggtgagcttt atctctggtg attctagcaa tacctattat 180
gcggatagcg tgaaaggccg ttttaccatt tcacgtgata attcgaaaaa caccctgtat 240
ctgcaaatga acagcctgcg tgcggaagat acggccgtgt attattgcgc gcgtactttt 300
atgcatggtc atcttggtgg tggtctttct atggattttt ggggccaagg caccctggtg 360
acggttagct ca 372
<210> 529
<211> 350
<212> DNA
<213> 智人
<400> 529
caggtgcaat tggtggaaag cggcggcggc ctggtgcaac cgggcggcag cctgcgtcta 60
gctgcgcggc ctccggattt acctttcgtt ctcattggct ttcttgggtg cgccaagccc 120
ctgggaaggg tctcgagtgg gtgagcaata tcaattatga tggtagctct acctattatg 180
cggatagcgt gaaaggccgt tttaccattt cacgtgataa ttcgaaaaac accctgtatc 240
tgcaaatgaa cagcctgcgt gcggaagata cggccgtgta ttattgcgcg cgtgatactt 300
atcttcattt tgattattgg ggccaaggca ccctggtgac ggttagctca 350
<210> 530
<211> 372
<212> DNA
<213> 智人
<400> 530
caggtgcaat tggtggaaag cggcggcggc ctggtgcaac cgggcggcag cctgcgtctg 60
agctgcgcgg cctccggatt taccttttct tcttatgtta tgaattgggt gcgccaagcc 120
cctgggaagg gtctcgagtg ggtgagcttt atctctggtg attctagcaa tacctattat 180
gcggatagcg tgaaaggccg ttttaccatt tcacgtgata attcgaaaaa caccctgtat 240
ctgcaaatga acagcctgcg tgcggaagat acggccgtgt attattgcgc gcgtactttt 300
atgcatggtc atcttggtgg tggtctttct atggattttt ggggccaagg caccctggtg 360
acggttagct ca 372
<210> 531
<211> 351
<212> DNA
<213> 智人
<400> 531
caggtgcaat tggtggaaag cggcggcggc ctggtgcaac cgggcggcag cctgcgtctg 60
agctgcgcgg cctccggatt tacctttcgt tctcattggc tttcttgggt gcgccaagcc 120
cctgggaagg gtctcgagtg ggtgagcaat atcaattatg atggtagctc tacctattat 180
gcggatagcg tgaaaggccg ttttaccatt tcacgtgata attcgaaaaa caccctgtat 240
ctgcaaatga acagcctgcg tgcggaagat acggccgtgt attattgcgc gcgtgatact 300
tatcttcatt ttgattattg gggccaaggc accctggtga cggttagctc a 351
<210> 532
<211> 348
<212> DNA
<213> 智人
<400> 532
caggtgcaat tggtggaaag cggcggcggc ctggtgcaac cgggcggcag cctgcgtctg 60
agctgcgcgg cctccggatt tacctttcgt tctcattggc tttcttgggt gcgccaagcc 120
cctgggaagg gtctcgagtg ggtgagcgtt actggtgttc atggtgatac ttattatgct 180
gattctgtta agggtcgttt taccatttca cgtgataatt cgaaaaacac cctgtatctg 240
caaatgaaca gcctgcgtgc ggaagatacg gccgtgtatt attgcgcgcg tgatacttat 300
cttcattttg attattgggg ccaaggcacc ctggtgacgg ttagctca 348
<210> 533
<211> 348
<212> DNA
<213> 智人
<400> 533
caggtgcaat tggtggaaag cggcggcggc ctggtgcaac cgggcggcag cctgcgtctg 60
agctgcgcgg cctccggatt tacctttcgt tctcattggc tttcttgggt gcgccaagcc 120
cctgggaagg gtctcgagtg ggtgagcgtt attggtaatt ggggtgatac ttattatgct 180
gattctgtta agggtcgttt taccatttca cgtgataatt cgaaaaacac cctgtatctg 240
caaatgaaca gcctgcgtgc ggaagatacg gccgtgtatt attgcgcgcg tgatacttat 300
cttcattttg attattgggg ccaaggcacc ctggtgacgg ttagctca 348
<210> 534
<211> 348
<212> DNA
<213> 智人
<400> 534
caggtgcaat tggtggaaag cggcggcggc ctggtgcaac cgggcggcag cctgcgtctg 60
agctgcgcgg cctccggatt tacctttcgt tctcattggc tttcttgggt gcgccaagcc 120
cctgggaagg gtctcgagtg ggtgagcgtt actactcatc agggttatac ttattatgct 180
gattctgtta agggtcgttt taccatttca cgtgataatt cgaaaaacac cctgtatctg 240
caaatgaaca gcctgcgtgc ggaagatacg gccgtgtatt attgcgcgcg tgatacttat 300
cttcattttg attattgggg ccaaggcacc ctggtgacgg ttagctca 348
<210> 535
<211> 348
<212> DNA
<213> 智人
<400> 535
caggtgcaat tggtggaaag cggcggcggc ctggtgcaac cgggcggcag cctgcgtctg 60
agctgcgcgg cctccggatt tacctttcgt tctcattggc tttcttgggt gcgccaagcc 120
cctgggaagg gtctcgagtg ggtgagcgct actaatcgtt atggttatac ttattatgct 180
gattctgtta agggtcgttt taccatttca cgtgataatt cgaaaaacac cctgtatctg 240
caaatgaaca gcctgcgtgc ggaagatacg gccgtgtatt attgcgcgcg tgatacttat 300
cttcattttg attattgggg ccaaggcacc ctggtgacgg ttagctca 348
<210> 536
<211> 351
<212> DNA
<213> 智人
<400> 536
caggtgcaat tggtggaaag cggcggcggc ctggtgcaac cgggcggcag cctgcgtctg 60
agctgcgcgg cctccggatt tacctttcgt tctcattggc tttcttgggt gcgccaagcc 120
cctgggaagg gtctcgagtg ggtgagcaat atcaattatg atggtagctc tacctattat 180
gcggatagcg tgaaaggccg ttttaccatt tcacgtgata attcgaaaaa caccctgtat 240
ctgcaaatga acagcctgcg tgcggaagat acggccgtgt attattgcgc gcgtgatact 300
tatcttcatt ttgattattg gggccaaggc accctggtga cggttagctc a 351
<210> 537
<211> 348
<212> DNA
<213> 智人
<400> 537
caggtgcaat tggtggaaag cggcggcggc ctggtgcaac cgggcggcag cctgcgtctg 60
agctgcgcgg cctccggatt tacctttcgt tctcattggc tttcttgggt gcgccaagcc 120
cctgggaagg gtctcgagtg ggtgagcgtt attactcctt atggtgatac ttattatgct 180
gattctgtta agggtcgttt taccatttca cgtgataatt cgaaaaacac cctgtatctg 240
caaatgaaca gcctgcgtgc ggaagatacg gccgtgtatt attgcgcgcg tgatacttat 300
cttcattttg attattgggg ccaaggcacc ctggtgacgg ttagctca 348
<210> 538
<211> 348
<212> DNA
<213> 智人
<400> 538
caggtgcaat tggtggaaag cggcggcggc ctggtgcaac cgggcggcag cctgcgtctg 60
agctgcgcgg cctccggatt tacctttcgt tctcattggc tttcttgggt gcgccaagcc 120
cctgggaagg gtctcgagtg ggtgagcgtt attactcctt atggtgatac ttattatgct 180
gattctgtta agggtcgttt taccatttca cgtgataatt cgaaaaacac cctgtatctg 240
caaatgaaca gcctgcgtgc ggaagatacg gccgtgtatt attgcgcgcg tgatacttat 300
cttcattttg attattgggg ccaaggcacc ctggtgacgg ttagctca 348
<210> 539
<211> 330
<212> DNA
<213> 智人
<400> 539
gatatcgaac tgacccagcc gccttcagtg agcgttgcac caggtcagac cgcgcgtatc 60
tcgtgtagcg gcgataatat tggttctttt tatgttcatt ggtaccagca gaaacccggg 120
caggcgccag ttcttgtgat ttatgatgat aataatcgtc cctcaggcat cccggaacgc 180
tttagcggat ccaacagcgg caacaccgcg accctgacca ttagcggcac tcaggcggaa 240
gacgaagcgg attattattg cggttcttgg gctggttctt ctggttctta tgtgtttggc 300
ggccgcacga agttaaccgt tcttggccag 330
<210> 540
<211> 339
<212> DNA
<213> 智人
<400> 540
gatatcgcac tgacccagcc agcttcagtg agcggctcac caggtcagag cattaccatc 60
tcgtgtacgg gtactagcag cgatgttggt gatattaatg atgtgtcttg gtaccagcag 120
catcccggga aggcgccgaa acttatgatt tatgatgtta ataatcgtcc ctcaggcgtg 180
agcaaccgtt ttagcggatc caaaagcggc aacaccgcga gcctgaccat tagcggcctg 240
caagcggaag acgaagcgga ttattattgc tcttcttatg gtgagtctct tacttcttat 300
gtgtttggcg gcggcacgaa gttaaccgtt cttggccag 339
<210> 541
<211> 330
<212> DNA
<213> 智人
<400> 541
gatatcgaac tgacccagcc gccttcagtg agcgttgcac caggtcagac cgcgcgtatc 60
tcgtgtagcg gcgataatat tggttctttt tatgttcatt ggtaccagca gaaacccggg 120
caggcgccag ttcttgtgat ttatgatgat aataatcgtc cctcaggcat cccggaacgc 180
tttagcggat ccaacagcgg caacaccgcg accctgacca ttagcggcac tcaggcggaa 240
gacgaagcgg attattattg cgcttcttgg actggtgttg agcctgatta tgtgtttggc 300
ggcggcacga agttaaccgt tcttggccag 330
<210> 542
<211> 339
<212> DNA
<213> 智人
<400> 542
gatatcgcac tgacccagcc agcttcagtg agcggctcac caggtcagag cattaccatc 60
tcgtgtacgg gtactagcag cgatgttggt gatattaatg atgtgtcttg gtaccagcag 120
catcccggga aggcgccgaa acttatgatt tatgatgtta ataatcgtcc ctcaggcgtg 180
agcaaccgtt ttagcggatc caaaagcggc aacaccgcga gcctgaccat tagcggcctg 240
caagcggaag acgaagcgga ttattattgc cagtcttatg ctggttctta tctttctgag 300
gtgtttggcg gcggcacgaa gttaaccgtt cttggccag 339
<210> 543
<211> 339
<212> DNA
<213> 智人
<400> 543
gatatcgcac tgacccagcc agcttcagtg agcggctcac caggtcagag cattaccatc 60
tcgtgtacgg gtactagcag cgatgttggt gatattaatg atgtgtcttg gtaccagcag 120
catcccggga aggcgccgaa acttatgatt tatgatgtta ataatcgtcc ctcaggcgtg 180
agcaaccgtt ttagcggatc caaaagcggc aacaccgcga gcctgaccat tagcggcctg 240
caagcggaag acgaagcgga ttattattgc tcttcttatg gtgagtctct tacttcttat 300
gtgtttggcg gcggcacgaa gttaaccgtt cttggccag 339
<210> 544
<211> 339
<212> DNA
<213> 智人
<400> 544
gatatcgcac tgacccagcc agcttcagtg agcggctcac caggtcagag cattaccatc 60
tcgtgtacgg gtactagcag cgatgttggt gatattaatg atgtgtcttg gtaccagcag 120
catcccggga aggcgccgaa acttatgatt tatgatgtta ataatcgtcc ctcaggcgtg 180
agcaaccgtt ttagcggatc caaaagcggc aacaccgcga gcctgaccat tagcggcctg 240
caagcggaag acgaagcgga ttattattgc tcttcttatg gtgagtctct tacttcttat 300
gtgtttggcg gcggcacgaa gttaaccgtt cttggccag 339
<210> 545
<211> 339
<212> DNA
<213> 智人
<400> 545
gatatcgcac tgacccagcc agcttcagtg agcggctcac caggtcagag cattaccatc 60
tcgtgtacgg gtactagcag cgatgttggt gatattaatg atgtgtcttg gtaccagcag 120
catcccggga aggcgccgaa acttatgatt tatgatgtta ataatcgtcc ctcaggcgtg 180
agcaaccgtt ttagcggatc caaaagcggc aacaccgcga gcctgaccat tagcggcctg 240
caagcggaag acgaagcgga ttattattgc tcttcttatg gtgagtctct tacttcttat 300
gtgtttggcg gcggcacgaa gttaaccgtt cttggccag 339
<210> 546
<211> 339
<212> DNA
<213> 智人
<400> 546
gatatcgcac tgacccagcc agcttcagtg agcggctcac caggtcagag cattaccatc 60
tcgtgtacgg gtactagcag cgatgttggt gatattaatg atgtgtcttg gtaccagcag 120
catcccggga aggcgccgaa acttatgatt tatgatgtta ataatcgtcc ctcaggcgtg 180
agcaaccgtt ttagcggatc caaaagcggc aacaccgcga gcctgaccat tagcggcctg 240
caagcggaag acgaagcgga ttattattgc tcttcttatg gtgagtctct tacttcttat 300
gtgtttggcg gcggcacgaa gttaaccgtt cttggccag 339
<210> 547
<211> 339
<212> DNA
<213> 智人
<400> 547
gatatcgcac tgacccagcc agcttcagtg agcggctcac caggtcagag cattaccatc 60
tcgtgtacgg gtactagcag cgatgttggt gatattaatg atgtgtcttg gtaccagcag 120
catcccggga aggcgccgaa acttatgatt tatgatgtta ataatcgtcc ctcaggcgtg 180
agcaaccgtt ttagcggatc caaaagcggc aacaccgcga gcctgaccat tagcggcctg 240
caagcggaag acgaagcgga ttattattgc tctacttatg atggtcctgg tctttctgag 300
gtgtttggcg gcggcacgaa gttaaccgtt cttggccag 339
<210> 548
<211> 339
<212> DNA
<213> 智人
<400> 548
gatatcgcac tgacccagcc agcttcagtg agcggctcac caggtcagag cattaccatc 60
tcgtgtacgg gtactagcag cgatgttggt gatattaatg atgtgtcttg gtaccagcag 120
catcccggga aggcgccgaa acttatgatt tatgatgtta ataatcgtcc ctcaggcgtg 180
agcaaccgtt ttagcggatc caaaagcggc aacaccgcga gcctgaccat tagcggcctg 240
caagcggaag acgaagcgga ttattattgc tcttcttatg gtgagtctct tacttcttat 300
gtgtttggcg gcggcacgaa gttaaccgtt cttggccag 339
<210> 549
<211> 339
<212> DNA
<213> 智人
<400> 549
gatatcgcac tgacccagcc agcttcagtg agcggctcac caggtcagag cattaccatc 60
tcgtgtacgg gtactagcag cgatgttggt gatattaatg atgtgtcttg gtaccagcag 120
catcccggga aggcgccgaa acttatgatt tatgatgtta ataatcgtcc ctcaggcgtg 180
agcaaccgtt ttagcggatc caaaagcggc aacaccgcga gcctgaccat tagcggcctg 240
caagcggaag acgaagcgga ttattattgc tctacttatg atggtcctgg tctttctgag 300
gtgtttggcg gcggcacgaa gttaaccgtt cttggccag 339
<210> 550
<211> 469
<212> PRT
<213> 智人
<400> 550
Met Ala Trp Val Trp Thr Leu Pro Phe Leu Met Ala Ala Ala Gln Ser
1 5 10 15
Val Gln Ala Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln
20 25 30
Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe
35 40 45
Ser Ser Tyr Val Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Glu Trp Val Ser Phe Ile Ser Gly Asp Ser Ser Asn Thr Tyr Tyr Ala
65 70 75 80
Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn
85 90 95
Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Thr Phe Met His Gly His Leu Gly Gly Gly Leu
115 120 125
Ser Met Asp Phe Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala
130 135 140
Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser
145 150 155 160
Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe
165 170 175
Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly
180 185 190
Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu
195 200 205
Ser Ser Val Val Thr Val Pro Ser Ser Asn Phe Gly Thr Gln Thr Tyr
210 215 220
Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Thr
225 230 235 240
Val Glu Arg Lys Cys Cys Val Glu Cys Pro Pro Cys Pro Ala Pro Pro
245 250 255
Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
260 265 270
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
275 280 285
Ser His Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val
290 295 300
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser
305 310 315 320
Thr Phe Arg Val Val Ser Val Leu Thr Val Val His Gln Asp Trp Leu
325 330 335
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ala
340 345 350
Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro
355 360 365
Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln
370 375 380
Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
385 390 395 400
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
405 410 415
Pro Pro Met Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu
420 425 430
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser
435 440 445
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
450 455 460
Leu Ser Pro Gly Lys
465
<210> 551
<211> 462
<212> PRT
<213> 智人
<400> 551
Met Ala Trp Val Trp Thr Leu Pro Phe Leu Met Ala Ala Ala Gln Ser
1 5 10 15
Val Gln Ala Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln
20 25 30
Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe
35 40 45
Arg Ser His Trp Leu Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Glu Trp Val Ser Asn Ile Asn Tyr Asp Gly Ser Ser Thr Tyr Tyr Ala
65 70 75 80
Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn
85 90 95
Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Asp Thr Tyr Leu His Phe Asp Tyr Trp Gly Gln
115 120 125
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
130 135 140
Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala
145 150 155 160
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
165 170 175
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
180 185 190
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
195 200 205
Ser Ser Asn Phe Gly Thr Gln Thr Tyr Thr Cys Asn Val Asp His Lys
210 215 220
Pro Ser Asn Thr Lys Val Asp Lys Thr Val Glu Arg Lys Cys Cys Val
225 230 235 240
Glu Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe
245 250 255
Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro
260 265 270
Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val
275 280 285
Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr
290 295 300
Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Val Val Ser Val
305 310 315 320
Leu Thr Val Val His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys
325 330 335
Lys Val Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser
340 345 350
Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro
355 360 365
Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val
370 375 380
Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly
385 390 395 400
Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Met Leu Asp Ser Asp
405 410 415
Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp
420 425 430
Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His
435 440 445
Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
450 455 460
<210> 552
<211> 469
<212> PRT
<213> 智人
<400> 552
Met Ala Trp Val Trp Thr Leu Pro Phe Leu Met Ala Ala Ala Gln Ser
1 5 10 15
Val Gln Ala Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln
20 25 30
Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe
35 40 45
Ser Ser Tyr Val Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Glu Trp Val Ser Phe Ile Ser Gly Asp Ser Ser Asn Thr Tyr Tyr Ala
65 70 75 80
Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn
85 90 95
Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Thr Phe Met His Gly His Leu Gly Gly Gly Leu
115 120 125
Ser Met Asp Phe Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala
130 135 140
Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser
145 150 155 160
Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe
165 170 175
Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly
180 185 190
Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu
195 200 205
Ser Ser Val Val Thr Val Pro Ser Ser Asn Phe Gly Thr Gln Thr Tyr
210 215 220
Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Thr
225 230 235 240
Val Glu Arg Lys Cys Cys Val Glu Cys Pro Pro Cys Pro Ala Pro Pro
245 250 255
Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
260 265 270
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
275 280 285
Ser His Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val
290 295 300
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser
305 310 315 320
Thr Phe Arg Val Val Ser Val Leu Thr Val Val His Gln Asp Trp Leu
325 330 335
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ala
340 345 350
Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro
355 360 365
Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln
370 375 380
Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
385 390 395 400
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
405 410 415
Pro Pro Met Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu
420 425 430
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser
435 440 445
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
450 455 460
Leu Ser Pro Gly Lys
465
<210> 553
<211> 462
<212> PRT
<213> 智人
<400> 553
Met Ala Trp Val Trp Thr Leu Pro Phe Leu Met Ala Ala Ala Gln Ser
1 5 10 15
Val Gln Ala Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln
20 25 30
Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe
35 40 45
Arg Ser His Trp Leu Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Glu Trp Val Ser Asn Ile Asn Tyr Asp Gly Ser Ser Thr Tyr Tyr Ala
65 70 75 80
Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn
85 90 95
Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Asp Thr Tyr Leu His Phe Asp Tyr Trp Gly Gln
115 120 125
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
130 135 140
Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala
145 150 155 160
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
165 170 175
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
180 185 190
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
195 200 205
Ser Ser Asn Phe Gly Thr Gln Thr Tyr Thr Cys Asn Val Asp His Lys
210 215 220
Pro Ser Asn Thr Lys Val Asp Lys Thr Val Glu Arg Lys Cys Cys Val
225 230 235 240
Glu Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe
245 250 255
Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro
260 265 270
Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val
275 280 285
Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr
290 295 300
Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Val Val Ser Val
305 310 315 320
Leu Thr Val Val His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys
325 330 335
Lys Val Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser
340 345 350
Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro
355 360 365
Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val
370 375 380
Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly
385 390 395 400
Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Met Leu Asp Ser Asp
405 410 415
Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp
420 425 430
Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His
435 440 445
Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
450 455 460
<210> 554
<211> 461
<212> PRT
<213> 智人
<400> 554
Met Ala Trp Val Trp Thr Leu Pro Phe Leu Met Ala Ala Ala Gln Ser
1 5 10 15
Val Gln Ala Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln
20 25 30
Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe
35 40 45
Arg Ser His Trp Leu Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Glu Trp Val Ser Val Thr Gly Val His Gly Asp Thr Tyr Tyr Ala Asp
65 70 75 80
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr
85 90 95
Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
100 105 110
Tyr Cys Ala Arg Asp Thr Tyr Leu His Phe Asp Tyr Trp Gly Gln Gly
115 120 125
Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
130 135 140
Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu
145 150 155 160
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
165 170 175
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
180 185 190
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
195 200 205
Ser Asn Phe Gly Thr Gln Thr Tyr Thr Cys Asn Val Asp His Lys Pro
210 215 220
Ser Asn Thr Lys Val Asp Lys Thr Val Glu Arg Lys Cys Cys Val Glu
225 230 235 240
Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu
245 250 255
Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu
260 265 270
Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Gln
275 280 285
Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys
290 295 300
Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Val Val Ser Val Leu
305 310 315 320
Thr Val Val His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys
325 330 335
Val Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys
340 345 350
Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser
355 360 365
Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys
370 375 380
Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln
385 390 395 400
Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Met Leu Asp Ser Asp Gly
405 410 415
Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln
420 425 430
Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn
435 440 445
His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
450 455 460
<210> 555
<211> 461
<212> PRT
<213> 智人
<400> 555
Met Ala Trp Val Trp Thr Leu Pro Phe Leu Met Ala Ala Ala Gln Ser
1 5 10 15
Val Gln Ala Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln
20 25 30
Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe
35 40 45
Arg Ser His Trp Leu Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Glu Trp Val Ser Val Ile Gly Asn Trp Gly Asp Thr Tyr Tyr Ala Asp
65 70 75 80
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr
85 90 95
Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
100 105 110
Tyr Cys Ala Arg Asp Thr Tyr Leu His Phe Asp Tyr Trp Gly Gln Gly
115 120 125
Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
130 135 140
Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu
145 150 155 160
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
165 170 175
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
180 185 190
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
195 200 205
Ser Asn Phe Gly Thr Gln Thr Tyr Thr Cys Asn Val Asp His Lys Pro
210 215 220
Ser Asn Thr Lys Val Asp Lys Thr Val Glu Arg Lys Cys Cys Val Glu
225 230 235 240
Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu
245 250 255
Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu
260 265 270
Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Gln
275 280 285
Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys
290 295 300
Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Val Val Ser Val Leu
305 310 315 320
Thr Val Val His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys
325 330 335
Val Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys
340 345 350
Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser
355 360 365
Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys
370 375 380
Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln
385 390 395 400
Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Met Leu Asp Ser Asp Gly
405 410 415
Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln
420 425 430
Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn
435 440 445
His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
450 455 460
<210> 556
<211> 461
<212> PRT
<213> 智人
<400> 556
Met Ala Trp Val Trp Thr Leu Pro Phe Leu Met Ala Ala Ala Gln Ser
1 5 10 15
Val Gln Ala Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln
20 25 30
Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe
35 40 45
Arg Ser His Trp Leu Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Glu Trp Val Ser Val Thr Thr His Gln Gly Tyr Thr Tyr Tyr Ala Asp
65 70 75 80
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr
85 90 95
Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
100 105 110
Tyr Cys Ala Arg Asp Thr Tyr Leu His Phe Asp Tyr Trp Gly Gln Gly
115 120 125
Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
130 135 140
Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu
145 150 155 160
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
165 170 175
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
180 185 190
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
195 200 205
Ser Asn Phe Gly Thr Gln Thr Tyr Thr Cys Asn Val Asp His Lys Pro
210 215 220
Ser Asn Thr Lys Val Asp Lys Thr Val Glu Arg Lys Cys Cys Val Glu
225 230 235 240
Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu
245 250 255
Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu
260 265 270
Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Gln
275 280 285
Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys
290 295 300
Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Val Val Ser Val Leu
305 310 315 320
Thr Val Val His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys
325 330 335
Val Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys
340 345 350
Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser
355 360 365
Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys
370 375 380
Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln
385 390 395 400
Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Met Leu Asp Ser Asp Gly
405 410 415
Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln
420 425 430
Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn
435 440 445
His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
450 455 460
<210> 557
<211> 465
<212> PRT
<213> 智人
<400> 557
Met Lys His Leu Trp Phe Phe Leu Leu Leu Val Ala Ala Pro Arg Trp
1 5 10 15
Val Leu Ser Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln
20 25 30
Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe
35 40 45
Arg Ser His Trp Leu Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Glu Trp Val Ser Ala Thr Asn Arg Tyr Gly Tyr Thr Tyr Tyr Ala Asp
65 70 75 80
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr
85 90 95
Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
100 105 110
Tyr Cys Ala Arg Asp Thr Tyr Leu His Phe Asp Tyr Trp Gly Gln Gly
115 120 125
Thr Leu Val Thr Val Ser Ser Ala Lys Thr Thr Ala Pro Ser Val Tyr
130 135 140
Pro Leu Ala Pro Val Cys Gly Asp Thr Thr Gly Ser Ser Val Thr Leu
145 150 155 160
Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val Thr Leu Thr Trp
165 170 175
Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr Phe Pro Ala Val Leu
180 185 190
Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr Val Thr Ser Ser
195 200 205
Thr Trp Pro Ser Gln Ser Ile Thr Cys Asn Val Ala His Pro Ala Ser
210 215 220
Ser Thr Lys Val Asp Lys Lys Ile Glu Pro Arg Gly Pro Thr Ile Lys
225 230 235 240
Pro Cys Pro Pro Cys Lys Cys Pro Ala Pro Asn Leu Leu Gly Gly Pro
245 250 255
Ser Val Phe Ile Phe Pro Pro Lys Ile Lys Asp Val Leu Met Ile Ser
260 265 270
Leu Ser Pro Ile Val Thr Cys Val Val Val Asp Val Ser Glu Asp Asp
275 280 285
Pro Asp Val Gln Ile Ser Trp Phe Val Asn Asn Val Glu Val His Thr
290 295 300
Ala Gln Thr Gln Thr His Arg Glu Asp Tyr Asn Ser Thr Leu Arg Val
305 310 315 320
Val Ser Ala Leu Pro Ile Gln His Gln Asp Trp Met Ser Gly Lys Glu
325 330 335
Phe Lys Cys Lys Val Asn Asn Lys Asp Leu Pro Ala Pro Ile Glu Arg
340 345 350
Thr Ile Ser Lys Pro Lys Gly Ser Val Arg Ala Pro Gln Val Tyr Val
355 360 365
Leu Pro Pro Pro Glu Glu Glu Met Thr Lys Lys Gln Val Thr Leu Thr
370 375 380
Cys Met Val Thr Asp Phe Met Pro Glu Asp Ile Tyr Val Glu Trp Thr
385 390 395 400
Asn Asn Gly Lys Thr Glu Leu Asn Tyr Lys Asn Thr Glu Pro Val Leu
405 410 415
Asp Ser Asp Gly Ser Tyr Phe Met Tyr Ser Lys Leu Arg Val Glu Lys
420 425 430
Lys Asn Trp Val Glu Arg Asn Ser Tyr Ser Cys Ser Val Val His Glu
435 440 445
Gly Leu His Asn His His Thr Thr Lys Ser Phe Ser Arg Thr Pro Gly
450 455 460
Lys
465
<210> 558
<211> 462
<212> PRT
<213> 智人
<400> 558
Met Ala Trp Val Trp Thr Leu Pro Phe Leu Met Ala Ala Ala Gln Ser
1 5 10 15
Val Gln Ala Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln
20 25 30
Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe
35 40 45
Arg Ser His Trp Leu Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Glu Trp Val Ser Asn Ile Asn Tyr Asp Gly Ser Ser Thr Tyr Tyr Ala
65 70 75 80
Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn
85 90 95
Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Ala Arg Asp Thr Tyr Leu His Phe Asp Tyr Trp Gly Gln
115 120 125
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
130 135 140
Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala
145 150 155 160
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
165 170 175
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
180 185 190
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
195 200 205
Ser Ser Asn Phe Gly Thr Gln Thr Tyr Thr Cys Asn Val Asp His Lys
210 215 220
Pro Ser Asn Thr Lys Val Asp Lys Thr Val Glu Arg Lys Cys Cys Val
225 230 235 240
Glu Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe
245 250 255
Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro
260 265 270
Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val
275 280 285
Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr
290 295 300
Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Val Val Ser Val
305 310 315 320
Leu Thr Val Val His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys
325 330 335
Lys Val Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser
340 345 350
Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro
355 360 365
Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val
370 375 380
Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly
385 390 395 400
Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Met Leu Asp Ser Asp
405 410 415
Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp
420 425 430
Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His
435 440 445
Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
450 455 460
<210> 559
<211> 461
<212> PRT
<213> 智人
<400> 559
Met Ala Trp Val Trp Thr Leu Pro Phe Leu Met Ala Ala Ala Gln Ser
1 5 10 15
Val Gln Ala Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln
20 25 30
Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe
35 40 45
Arg Ser His Trp Leu Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Glu Trp Val Ser Val Ile Thr Pro Tyr Gly Asp Thr Tyr Tyr Ala Asp
65 70 75 80
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr
85 90 95
Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
100 105 110
Tyr Cys Ala Arg Asp Thr Tyr Leu His Phe Asp Tyr Trp Gly Gln Gly
115 120 125
Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
130 135 140
Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu
145 150 155 160
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
165 170 175
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
180 185 190
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
195 200 205
Ser Asn Phe Gly Thr Gln Thr Tyr Thr Cys Asn Val Asp His Lys Pro
210 215 220
Ser Asn Thr Lys Val Asp Lys Thr Val Glu Arg Lys Cys Cys Val Glu
225 230 235 240
Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu
245 250 255
Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu
260 265 270
Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Gln
275 280 285
Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys
290 295 300
Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Val Val Ser Val Leu
305 310 315 320
Thr Val Val His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys
325 330 335
Val Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys
340 345 350
Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser
355 360 365
Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys
370 375 380
Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln
385 390 395 400
Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Met Leu Asp Ser Asp Gly
405 410 415
Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln
420 425 430
Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn
435 440 445
His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
450 455 460
<210> 560
<211> 461
<212> PRT
<213> 智人
<400> 560
Met Ala Trp Val Trp Thr Leu Pro Phe Leu Met Ala Ala Ala Gln Ser
1 5 10 15
Val Gln Ala Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln
20 25 30
Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe
35 40 45
Arg Ser His Trp Leu Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Glu Trp Val Ser Val Ile Thr Pro Tyr Gly Asp Thr Tyr Tyr Ala Asp
65 70 75 80
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr
85 90 95
Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
100 105 110
Tyr Cys Ala Arg Asp Thr Tyr Leu His Phe Asp Tyr Trp Gly Gln Gly
115 120 125
Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
130 135 140
Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu
145 150 155 160
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
165 170 175
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
180 185 190
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
195 200 205
Ser Asn Phe Gly Thr Gln Thr Tyr Thr Cys Asn Val Asp His Lys Pro
210 215 220
Ser Asn Thr Lys Val Asp Lys Thr Val Glu Arg Lys Cys Cys Val Glu
225 230 235 240
Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu
245 250 255
Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu
260 265 270
Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Gln
275 280 285
Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys
290 295 300
Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Val Val Ser Val Leu
305 310 315 320
Thr Val Val His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys
325 330 335
Val Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys
340 345 350
Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser
355 360 365
Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys
370 375 380
Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln
385 390 395 400
Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Met Leu Asp Ser Asp Gly
405 410 415
Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln
420 425 430
Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn
435 440 445
His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
450 455 460
<210> 561
<211> 130
<212> PRT
<213> 智人
<400> 561
Met Ser Val Leu Thr Gln Val Leu Ala Leu Leu Leu Leu Trp Leu Thr
1 5 10 15
Gly Thr Arg Cys Asp Ile Glu Leu Thr Gln Pro Pro Ser Val Ser Val
20 25 30
Ala Pro Gly Gln Thr Ala Arg Ile Ser Cys Ser Gly Asp Asn Ile Gly
35 40 45
Ser Phe Tyr Val His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val
50 55 60
Leu Val Ile Tyr Asp Asp Asn Asn Arg Pro Ser Gly Ile Pro Glu Arg
65 70 75 80
Phe Ser Gly Ser Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Gly
85 90 95
Thr Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Gly Ser Trp Ala Gly
100 105 110
Ser Ser Gly Ser Tyr Val Phe Gly Gly Arg Thr Lys Leu Thr Val Leu
115 120 125
Gly Gln
130
<210> 562
<211> 237
<212> PRT
<213> 智人
<400> 562
Met Ser Val Leu Thr Gln Val Leu Ala Leu Leu Leu Leu Trp Leu Thr
1 5 10 15
Gly Thr Arg Cys Asp Ile Ala Leu Thr Gln Pro Ala Ser Val Ser Gly
20 25 30
Ser Pro Gly Gln Ser Ile Thr Ile Ser Cys Thr Gly Thr Ser Ser Asp
35 40 45
Val Gly Asp Ile Asn Asp Val Ser Trp Tyr Gln Gln His Pro Gly Lys
50 55 60
Ala Pro Lys Leu Met Ile Tyr Asp Val Asn Asn Arg Pro Ser Gly Val
65 70 75 80
Ser Asn Arg Phe Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr
85 90 95
Ile Ser Gly Leu Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser
100 105 110
Tyr Gly Glu Ser Leu Thr Ser Tyr Val Phe Gly Gly Gly Thr Lys Leu
115 120 125
Thr Val Leu Gly Gln Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro
130 135 140
Pro Ser Ser Glu Glu Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu
145 150 155 160
Ile Ser Asp Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp
165 170 175
Ser Ser Pro Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gln
180 185 190
Ser Asn Asn Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu
195 200 205
Gln Trp Lys Ser His Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly
210 215 220
Ser Thr Val Glu Lys Thr Val Ala Pro Thr Glu Cys Ser
225 230 235
<210> 563
<211> 234
<212> PRT
<213> 智人
<400> 563
Met Ser Val Leu Thr Gln Val Leu Ala Leu Leu Leu Leu Trp Leu Thr
1 5 10 15
Gly Thr Arg Cys Asp Ile Glu Leu Thr Gln Pro Pro Ser Val Ser Val
20 25 30
Ala Pro Gly Gln Thr Ala Arg Ile Ser Cys Ser Gly Asp Asn Ile Gly
35 40 45
Ser Phe Tyr Val His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val
50 55 60
Leu Val Ile Tyr Asp Asp Asn Asn Arg Pro Ser Gly Ile Pro Glu Arg
65 70 75 80
Phe Ser Gly Ser Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Gly
85 90 95
Thr Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Ser Trp Thr Gly
100 105 110
Val Glu Pro Asp Tyr Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
115 120 125
Gly Gln Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro Pro Ser Ser
130 135 140
Glu Glu Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp
145 150 155 160
Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Ser Ser Pro
165 170 175
Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn
180 185 190
Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys
195 200 205
Ser His Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val
210 215 220
Glu Lys Thr Val Ala Pro Thr Glu Cys Ser
225 230
<210> 564
<211> 237
<212> PRT
<213> 智人
<400> 564
Met Ser Val Leu Thr Gln Val Leu Ala Leu Leu Leu Leu Trp Leu Thr
1 5 10 15
Gly Thr Arg Cys Asp Ile Ala Leu Thr Gln Pro Ala Ser Val Ser Gly
20 25 30
Ser Pro Gly Gln Ser Ile Thr Ile Ser Cys Thr Gly Thr Ser Ser Asp
35 40 45
Val Gly Asp Ile Asn Asp Val Ser Trp Tyr Gln Gln His Pro Gly Lys
50 55 60
Ala Pro Lys Leu Met Ile Tyr Asp Val Asn Asn Arg Pro Ser Gly Val
65 70 75 80
Ser Asn Arg Phe Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr
85 90 95
Ile Ser Gly Leu Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Gln Ser
100 105 110
Tyr Ala Gly Ser Tyr Leu Ser Glu Val Phe Gly Gly Gly Thr Lys Leu
115 120 125
Thr Val Leu Gly Gln Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro
130 135 140
Pro Ser Ser Glu Glu Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu
145 150 155 160
Ile Ser Asp Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp
165 170 175
Ser Ser Pro Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gln
180 185 190
Ser Asn Asn Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu
195 200 205
Gln Trp Lys Ser His Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly
210 215 220
Ser Thr Val Glu Lys Thr Val Ala Pro Thr Glu Cys Ser
225 230 235
<210> 565
<211> 237
<212> PRT
<213> 智人
<400> 565
Met Ser Val Leu Thr Gln Val Leu Ala Leu Leu Leu Leu Trp Leu Thr
1 5 10 15
Gly Thr Arg Cys Asp Ile Ala Leu Thr Gln Pro Ala Ser Val Ser Gly
20 25 30
Ser Pro Gly Gln Ser Ile Thr Ile Ser Cys Thr Gly Thr Ser Ser Asp
35 40 45
Val Gly Asp Ile Asn Asp Val Ser Trp Tyr Gln Gln His Pro Gly Lys
50 55 60
Ala Pro Lys Leu Met Ile Tyr Asp Val Asn Asn Arg Pro Ser Gly Val
65 70 75 80
Ser Asn Arg Phe Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr
85 90 95
Ile Ser Gly Leu Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser
100 105 110
Tyr Gly Glu Ser Leu Thr Ser Tyr Val Phe Gly Gly Gly Thr Lys Leu
115 120 125
Thr Val Leu Gly Gln Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro
130 135 140
Pro Ser Ser Glu Glu Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu
145 150 155 160
Ile Ser Asp Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp
165 170 175
Ser Ser Pro Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gln
180 185 190
Ser Asn Asn Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu
195 200 205
Gln Trp Lys Ser His Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly
210 215 220
Ser Thr Val Glu Lys Thr Val Ala Pro Thr Glu Cys Ser
225 230 235
<210> 566
<211> 237
<212> PRT
<213> 智人
<400> 566
Met Ser Val Leu Thr Gln Val Leu Ala Leu Leu Leu Leu Trp Leu Thr
1 5 10 15
Gly Thr Arg Cys Asp Ile Ala Leu Thr Gln Pro Ala Ser Val Ser Gly
20 25 30
Ser Pro Gly Gln Ser Ile Thr Ile Ser Cys Thr Gly Thr Ser Ser Asp
35 40 45
Val Gly Asp Ile Asn Asp Val Ser Trp Tyr Gln Gln His Pro Gly Lys
50 55 60
Ala Pro Lys Leu Met Ile Tyr Asp Val Asn Asn Arg Pro Ser Gly Val
65 70 75 80
Ser Asn Arg Phe Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr
85 90 95
Ile Ser Gly Leu Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser
100 105 110
Tyr Gly Glu Ser Leu Thr Ser Tyr Val Phe Gly Gly Gly Thr Lys Leu
115 120 125
Thr Val Leu Gly Gln Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro
130 135 140
Pro Ser Ser Glu Glu Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu
145 150 155 160
Ile Ser Asp Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp
165 170 175
Ser Ser Pro Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gln
180 185 190
Ser Asn Asn Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu
195 200 205
Gln Trp Lys Ser His Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly
210 215 220
Ser Thr Val Glu Lys Thr Val Ala Pro Thr Glu Cys Ser
225 230 235
<210> 567
<211> 237
<212> PRT
<213> 智人
<400> 567
Met Ser Val Leu Thr Gln Val Leu Ala Leu Leu Leu Leu Trp Leu Thr
1 5 10 15
Gly Thr Arg Cys Asp Ile Ala Leu Thr Gln Pro Ala Ser Val Ser Gly
20 25 30
Ser Pro Gly Gln Ser Ile Thr Ile Ser Cys Thr Gly Thr Ser Ser Asp
35 40 45
Val Gly Asp Ile Asn Asp Val Ser Trp Tyr Gln Gln His Pro Gly Lys
50 55 60
Ala Pro Lys Leu Met Ile Tyr Asp Val Asn Asn Arg Pro Ser Gly Val
65 70 75 80
Ser Asn Arg Phe Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr
85 90 95
Ile Ser Gly Leu Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser
100 105 110
Tyr Gly Glu Ser Leu Thr Ser Tyr Val Phe Gly Gly Gly Thr Lys Leu
115 120 125
Thr Val Leu Gly Gln Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro
130 135 140
Pro Ser Ser Glu Glu Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu
145 150 155 160
Ile Ser Asp Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp
165 170 175
Ser Ser Pro Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gln
180 185 190
Ser Asn Asn Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu
195 200 205
Gln Trp Lys Ser His Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly
210 215 220
Ser Thr Val Glu Lys Thr Val Ala Pro Thr Glu Cys Ser
225 230 235
<210> 568
<211> 237
<212> PRT
<213> 智人
<400> 568
Met Ser Val Leu Thr Gln Val Leu Ala Leu Leu Leu Leu Trp Leu Thr
1 5 10 15
Gly Thr Arg Cys Asp Ile Ala Leu Thr Gln Pro Ala Ser Val Ser Gly
20 25 30
Ser Pro Gly Gln Ser Ile Thr Ile Ser Cys Thr Gly Thr Ser Ser Asp
35 40 45
Val Gly Asp Ile Asn Asp Val Ser Trp Tyr Gln Gln His Pro Gly Lys
50 55 60
Ala Pro Lys Leu Met Ile Tyr Asp Val Asn Asn Arg Pro Ser Gly Val
65 70 75 80
Ser Asn Arg Phe Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr
85 90 95
Ile Ser Gly Leu Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser
100 105 110
Tyr Gly Glu Ser Leu Thr Ser Tyr Val Phe Gly Gly Gly Thr Lys Leu
115 120 125
Thr Val Leu Gly Gln Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro
130 135 140
Pro Ser Ser Glu Glu Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu
145 150 155 160
Ile Ser Asp Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp
165 170 175
Ser Ser Pro Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gln
180 185 190
Ser Asn Asn Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu
195 200 205
Gln Trp Lys Ser His Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly
210 215 220
Ser Thr Val Glu Lys Thr Val Ala Pro Thr Glu Cys Ser
225 230 235
<210> 569
<211> 237
<212> PRT
<213> 智人
<400> 569
Met Ser Val Leu Thr Gln Val Leu Ala Leu Leu Leu Leu Trp Leu Thr
1 5 10 15
Gly Thr Arg Cys Asp Ile Ala Leu Thr Gln Pro Ala Ser Val Ser Gly
20 25 30
Ser Pro Gly Gln Ser Ile Thr Ile Ser Cys Thr Gly Thr Ser Ser Asp
35 40 45
Val Gly Asp Ile Asn Asp Val Ser Trp Tyr Gln Gln His Pro Gly Lys
50 55 60
Ala Pro Lys Leu Met Ile Tyr Asp Val Asn Asn Arg Pro Ser Gly Val
65 70 75 80
Ser Asn Arg Phe Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr
85 90 95
Ile Ser Gly Leu Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Thr
100 105 110
Tyr Asp Gly Pro Gly Leu Ser Glu Val Phe Gly Gly Gly Thr Lys Leu
115 120 125
Thr Val Leu Gly Gln Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro
130 135 140
Pro Ser Ser Glu Glu Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu
145 150 155 160
Ile Ser Asp Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp
165 170 175
Ser Ser Pro Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gln
180 185 190
Ser Asn Asn Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu
195 200 205
Gln Trp Lys Ser His Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly
210 215 220
Ser Thr Val Glu Lys Thr Val Ala Pro Thr Glu Cys Ser
225 230 235
<210> 570
<211> 237
<212> PRT
<213> 智人
<400> 570
Met Ser Val Leu Thr Gln Val Leu Ala Leu Leu Leu Leu Trp Leu Thr
1 5 10 15
Gly Thr Arg Cys Asp Ile Ala Leu Thr Gln Pro Ala Ser Val Ser Gly
20 25 30
Ser Pro Gly Gln Ser Ile Thr Ile Ser Cys Thr Gly Thr Ser Ser Asp
35 40 45
Val Gly Asp Ile Asn Asp Val Ser Trp Tyr Gln Gln His Pro Gly Lys
50 55 60
Ala Pro Lys Leu Met Ile Tyr Asp Val Asn Asn Arg Pro Ser Gly Val
65 70 75 80
Ser Asn Arg Phe Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr
85 90 95
Ile Ser Gly Leu Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser
100 105 110
Tyr Gly Glu Ser Leu Thr Ser Tyr Val Phe Gly Gly Gly Thr Lys Leu
115 120 125
Thr Val Leu Gly Gln Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro
130 135 140
Pro Ser Ser Glu Glu Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu
145 150 155 160
Ile Ser Asp Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp
165 170 175
Ser Ser Pro Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gln
180 185 190
Ser Asn Asn Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu
195 200 205
Gln Trp Lys Ser His Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly
210 215 220
Ser Thr Val Glu Lys Thr Val Ala Pro Thr Glu Cys Ser
225 230 235
<210> 571
<211> 237
<212> PRT
<213> 智人
<400> 571
Met Ser Val Leu Thr Gln Val Leu Ala Leu Leu Leu Leu Trp Leu Thr
1 5 10 15
Gly Thr Arg Cys Asp Ile Ala Leu Thr Gln Pro Ala Ser Val Ser Gly
20 25 30
Ser Pro Gly Gln Ser Ile Thr Ile Ser Cys Thr Gly Thr Ser Ser Asp
35 40 45
Val Gly Asp Ile Asn Asp Val Ser Trp Tyr Gln Gln His Pro Gly Lys
50 55 60
Ala Pro Lys Leu Met Ile Tyr Asp Val Asn Asn Arg Pro Ser Gly Val
65 70 75 80
Ser Asn Arg Phe Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr
85 90 95
Ile Ser Gly Leu Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Thr
100 105 110
Tyr Asp Gly Pro Gly Leu Ser Glu Val Phe Gly Gly Gly Thr Lys Leu
115 120 125
Thr Val Leu Gly Gln Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro
130 135 140
Pro Ser Ser Glu Glu Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu
145 150 155 160
Ile Ser Asp Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp
165 170 175
Ser Ser Pro Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gln
180 185 190
Ser Asn Asn Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu
195 200 205
Gln Trp Lys Ser His Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly
210 215 220
Ser Thr Val Glu Lys Thr Val Ala Pro Thr Glu Cys Ser
225 230 235
<210> 572
<211> 1410
<212> DNA
<213> 智人
<400> 572
atggcttggg tgtggacctt gccattcctg atggcagctg cccaaagcgt gcaggcccag 60
gtgcagctgg tcgagtctgg cggcggactg gtgcagcctg gcggcagcct gagactgagc 120
tgcgccgcca gcggcttcac cttcagcagc tacgtgatga actgggtgcg gcaggcccct 180
ggcaagggcc tggagtgggt gtccttcatc agcggcgaca gcagcaacac ctactacgcc 240
gacagcgtga agggccggtt caccatcagc cgggacaaca gcaagaacac cctgtacctg 300
cagatgaaca gcctgcgggc cgaggacacc gccgtgtact actgcgcccg gaccttcatg 360
cacggccacc tgggcggagg actgagcatg gatttctggg gccagggcac cctggtcacc 420
gtctcctcag cttccaccaa gggcccatcc gtcttccccc tggcgccctg ctccaggagc 480
acctccgaga gcacagcggc cctgggctgc ctggtcaagg actacttccc cgaaccggtg 540
acggtgtcgt ggaactcagg cgctctgacc agcggcgtgc acaccttccc agctgtccta 600
cagtcctcag gactctactc cctcagcagc gtggtgacag tgccctccag caacttcggc 660
acccagacct acacctgcaa cgtagatcac aagcccagca acaccaaggt ggacaagaca 720
gttgagcgca aatgttgtgt cgagtgccca ccgtgcccag caccacctgt ggcaggaccg 780
tcagtcttcc tcttcccccc aaaacccaag gacaccctca tgatctcccg gacccctgag 840
gtcacgtgcg tggtggtgga cgtgagccac gaagaccccg aggtccagtt caactggtac 900
gtggacggcg tggaggtgca taatgccaag acaaagccac gggaggagca gttcaacagc 960
acgttccgtg tggtcagcgt cctcaccgtt gtgcaccagg actggctgaa cggcaaggag 1020
tacaagtgca aggtctccaa caaaggcctc ccagccccca tcgagaaaac catctccaaa 1080
accaaagggc agccccgaga accacaggtg tacaccctgc ccccatcccg ggaggagatg 1140
accaagaacc aggtcagcct gacctgcctg gtcaaaggct tctaccccag cgacatcgcc 1200
gtggagtggg agagcaatgg gcagccggag aacaactaca agaccacacc tcccatgctg 1260
gactccgacg gctccttctt cctctacagc aagctcaccg tggacaagag caggtggcag 1320
caggggaacg tcttctcatg ctccgtgatg catgaggctc tgcacaacca ctacacgcag 1380
aagagcctct ccctgtctcc gggtaaatga 1410
<210> 573
<211> 1389
<212> DNA
<213> 智人
<400> 573
atggcttggg tgtggacctt gccattcctg atggcagctg cccaaggtgt ccaggcccag 60
gtgcagctgg tcgagagcgg cggagggctg gtgcagcctg gcggcagcct gagactgagc 120
tgcgccgcca gcggcttcac cttcagaagc cactggctgt cctgggtgcg gcaggcccct 180
ggcaagggcc tggaatgggt gtccaacatc aactacgacg gcagcagcac ctactacgcc 240
gacagcgtga agggccggtt caccatcagc cgggacaaca gcaagaacac cctgtacctg 300
cagatgaaca gcctgcgggc cgaggacacc gccgtgtact actgcgccag ggacacctac 360
ctgcacttcg actactgggg ccagggcacc ctggtcaccg tctcctcagc ttccaccaag 420
ggcccatccg tcttccccct ggcgccctgc tccaggagca cctccgagag cacagcggcc 480
ctgggctgcc tggtcaagga ctacttcccc gaaccggtga cggtgtcgtg gaactcaggc 540
gctctgacca gcggcgtgca caccttccca gctgtcctac agtcctcagg actctactcc 600
ctcagcagcg tggtgacagt gccctccagc aacttcggca cccagaccta cacctgcaac 660
gtagatcaca agcccagcaa caccaaggtg gacaagacag ttgagcgcaa atgttgtgtc 720
gagtgcccac cgtgcccagc accacctgtg gcaggaccgt cagtcttcct cttcccccca 780
aaacccaagg acaccctcat gatctcccgg acccctgagg tcacgtgcgt ggtggtggac 840
gtgagccacg aagaccccga ggtccagttc aactggtacg tggacggcgt ggaggtgcat 900
aatgccaaga caaagccacg ggaggagcag ttcaacagca cgttccgtgt ggtcagcgtc 960
ctcaccgttg tgcaccagga ctggctgaac ggcaaggagt acaagtgcaa ggtctccaac 1020
aaaggcctcc cagcccccat cgagaaaacc atctccaaaa ccaaagggca gccccgagaa 1080
ccacaggtgt acaccctgcc cccatcccgg gaggagatga ccaagaacca ggtcagcctg 1140
acctgcctgg tcaaaggctt ctaccccagc gacatcgccg tggagtggga gagcaatggg 1200
cagccggaga acaactacaa gaccacacct cccatgctgg actccgacgg ctccttcttc 1260
ctctacagca agctcaccgt ggacaagagc aggtggcagc aggggaacgt cttctcatgc 1320
tccgtgatgc atgaggctct gcacaaccac tacacgcaga agagcctctc cctgtctccg 1380
ggtaaatga 1389
<210> 574
<211> 1410
<212> DNA
<213> 智人
<400> 574
atggcttggg tgtggacctt gccattcctg atggcagctg cccaaagcgt gcaggcccag 60
gtgcagctgg tcgagtctgg cggcggactg gtgcagcctg gcggcagcct gagactgagc 120
tgcgccgcca gcggcttcac cttcagcagc tacgtgatga actgggtgcg gcaggcccct 180
ggcaagggcc tggagtgggt gtccttcatc agcggcgaca gcagcaacac ctactacgcc 240
gacagcgtga agggccggtt caccatcagc cgggacaaca gcaagaacac cctgtacctg 300
cagatgaaca gcctgcgggc cgaggacacc gccgtgtact actgcgcccg gaccttcatg 360
cacggccacc tgggcggagg actgagcatg gatttctggg gccagggcac cctggtcacc 420
gtctcctcag cttccaccaa gggcccatcc gtcttccccc tggcgccctg ctccaggagc 480
acctccgaga gcacagcggc cctgggctgc ctggtcaagg actacttccc cgaaccggtg 540
acggtgtcgt ggaactcagg cgctctgacc agcggcgtgc acaccttccc agctgtccta 600
cagtcctcag gactctactc cctcagcagc gtggtgacag tgccctccag caacttcggc 660
acccagacct acacctgcaa cgtagatcac aagcccagca acaccaaggt ggacaagaca 720
gttgagcgca aatgttgtgt cgagtgccca ccgtgcccag caccacctgt ggcaggaccg 780
tcagtcttcc tcttcccccc aaaacccaag gacaccctca tgatctcccg gacccctgag 840
gtcacgtgcg tggtggtgga cgtgagccac gaagaccccg aggtccagtt caactggtac 900
gtggacggcg tggaggtgca taatgccaag acaaagccac gggaggagca gttcaacagc 960
acgttccgtg tggtcagcgt cctcaccgtt gtgcaccagg actggctgaa cggcaaggag 1020
tacaagtgca aggtctccaa caaaggcctc ccagccccca tcgagaaaac catctccaaa 1080
accaaagggc agccccgaga accacaggtg tacaccctgc ccccatcccg ggaggagatg 1140
accaagaacc aggtcagcct gacctgcctg gtcaaaggct tctaccccag cgacatcgcc 1200
gtggagtggg agagcaatgg gcagccggag aacaactaca agaccacacc tcccatgctg 1260
gactccgacg gctccttctt cctctacagc aagctcaccg tggacaagag caggtggcag 1320
caggggaacg tcttctcatg ctccgtgatg catgaggctc tgcacaacca ctacacgcag 1380
aagagcctct ccctgtctcc gggtaaatga 1410
<210> 575
<211> 1389
<212> DNA
<213> 智人
<400> 575
atggcttggg tgtggacctt gccattcctg atggcagctg cccaaggtgt ccaggcccag 60
gtgcagctgg tcgagagcgg cggagggctg gtgcagcctg gcggcagcct gagactgagc 120
tgcgccgcca gcggcttcac cttcagaagc cactggctgt cctgggtgcg gcaggcccct 180
ggcaagggcc tggaatgggt gtccaacatc aactacgacg gcagcagcac ctactacgcc 240
gacagcgtga agggccggtt caccatcagc cgggacaaca gcaagaacac cctgtacctg 300
cagatgaaca gcctgcgggc cgaggacacc gccgtgtact actgcgccag ggacacctac 360
ctgcacttcg actactgggg ccagggcacc ctggtcaccg tctcctcagc ttccaccaag 420
ggcccatccg tcttccccct ggcgccctgc tccaggagca cctccgagag cacagcggcc 480
ctgggctgcc tggtcaagga ctacttcccc gaaccggtga cggtgtcgtg gaactcaggc 540
gctctgacca gcggcgtgca caccttccca gctgtcctac agtcctcagg actctactcc 600
ctcagcagcg tggtgacagt gccctccagc aacttcggca cccagaccta cacctgcaac 660
gtagatcaca agcccagcaa caccaaggtg gacaagacag ttgagcgcaa atgttgtgtc 720
gagtgcccac cgtgcccagc accacctgtg gcaggaccgt cagtcttcct cttcccccca 780
aaacccaagg acaccctcat gatctcccgg acccctgagg tcacgtgcgt ggtggtggac 840
gtgagccacg aagaccccga ggtccagttc aactggtacg tggacggcgt ggaggtgcat 900
aatgccaaga caaagccacg ggaggagcag ttcaacagca cgttccgtgt ggtcagcgtc 960
ctcaccgttg tgcaccagga ctggctgaac ggcaaggagt acaagtgcaa ggtctccaac 1020
aaaggcctcc cagcccccat cgagaaaacc atctccaaaa ccaaagggca gccccgagaa 1080
ccacaggtgt acaccctgcc cccatcccgg gaggagatga ccaagaacca ggtcagcctg 1140
acctgcctgg tcaaaggctt ctaccccaga gacatcgccg tggagtggga gagcaatggg 1200
cagccggaga acaactacaa gaccacacct cccatgctgg actccgacgg ctccttcttc 1260
ctctacagca agctcaccgt ggacaagagc aggtggcagc aggggaacgt cttctcatgc 1320
tccgtgatgc atgaggctct gcacaaccac tacacgcaga agagcctctc cctgtctccg 1380
ggtaaatga 1389
<210> 576
<211> 1386
<212> DNA
<213> 智人
<400> 576
atggcttggg tgtggacctt gccattcctg atggcagctg cccaaagtgt ccaggcccag 60
gtgcagctgg tcgagagcgg cggagggctg gtgcagcctg gcggcagcct gagactgagc 120
tgcgccgcca gcggcttcac cttcagaagc cactggctgt cctgggtgcg gcaggcccct 180
ggcaagggcc tggaatgggt gtccgtgacc ggcgtgcacg gcgacaccta ctacgccgac 240
agcgtgaagg gccggttcac catcagccgg gacaacagca agaacaccct gtacctgcag 300
atgaacagcc tgcgggccga ggacaccgcc gtgtactact gcgccaggga cacctacctg 360
cacttcgact actggggcca gggcaccctg gtcaccgtct cctcagcttc caccaagggc 420
ccatccgtct tccccctggc gccctgctcc aggagcacct ccgagagcac agcggccctg 480
ggctgcctgg tcaaggacta cttccccgaa ccggtgacgg tgtcgtggaa ctcaggcgct 540
ctgaccagcg gcgtgcacac cttcccagct gtcctacagt cctcaggact ctactccctc 600
agcagcgtgg tgacagtgcc ctccagcaac ttcggcaccc agacctacac ctgcaacgta 660
gatcacaagc ccagcaacac caaggtggac aagacagttg agcgcaaatg ttgtgtcgag 720
tgcccaccgt gcccagcacc acctgtggca ggaccgtcag tcttcctctt ccccccaaaa 780
cccaaggaca ccctcatgat ctcccggacc cctgaggtca cgtgcgtggt ggtggacgtg 840
agccacgaag accccgaggt ccagttcaac tggtacgtgg acggcgtgga ggtgcataat 900
gccaagacaa agccacggga ggagcagttc aacagcacgt tccgtgtggt cagcgtcctc 960
accgttgtgc accaggactg gctgaacggc aaggagtaca agtgcaaggt ctccaacaaa 1020
ggcctcccag cccccatcga gaaaaccatc tccaaaacca aagggcagcc ccgagaacca 1080
caggtgtaca ccctgccccc atcccgggag gagatgacca agaaccaggt cagcctgacc 1140
tgcctggtca aaggcttcta ccccagcgac atcgccgtgg agtgggagag caatgggcag 1200
ccggagaaca actacaagac cacacctccc atgctggact ccgacggctc cttcttcctc 1260
tacagcaagc tcaccgtgga caagagcagg tggcagcagg ggaacgtctt ctcatgctcc 1320
gtgatgcatg aggctctgca caaccactac acgcagaaga gcctctccct gtctccgggt 1380
aaatga 1386
<210> 577
<211> 1386
<212> DNA
<213> 智人
<400> 577
atggcttggg tgtggacctt gccattcctg atggcagctg cccaaagtgt ccaggcccag 60
gtgcagctgg tcgagagcgg cggagggctg gtgcagcctg gcggcagcct gagactgagc 120
tgcgccgcca gcggcttcac cttcagaagc cactggctgt cctgggtgcg gcaggcccct 180
ggcaagggcc tggaatgggt gtccgtgatc ggcaactggg gcgacaccta ctacgccgac 240
agcgtgaagg gccggttcac catcagccgg gacaacagca agaacaccct gtacctgcag 300
atgaacagcc tgcgggccga ggacaccgcc gtgtactact gcgccaggga cacctacctg 360
cacttcgact actggggcca gggcaccctg gtcaccgtct cctcagcttc caccaagggc 420
ccatccgtct tccccctggc gccctgctcc aggagcacct ccgagagcac agcggccctg 480
ggctgcctgg tcaaggacta cttccccgaa ccggtgacgg tgtcgtggaa ctcaggcgct 540
ctgaccagcg gcgtgcacac cttcccagct gtcctacagt cctcaggact ctactccctc 600
agcagcgtgg tgacagtgcc ctccagcaac ttcggcaccc agacctacac ctgcaacgta 660
gatcacaagc ccagcaacac caaggtggac aagacagttg agcgcaaatg ttgtgtcgag 720
tgcccaccgt gcccagcacc acctgtggca ggaccgtcag tcttcctctt ccccccaaaa 780
cccaaggaca ccctcatgat ctcccggacc cctgaggtca cgtgcgtggt ggtggacgtg 840
agccacgaag accccgaggt ccagttcaac tggtacgtgg acggcgtgga ggtgcataat 900
gccaagacaa agccacggga ggagcagttc aacagcacgt tccgtgtggt cagcgtcctc 960
accgttgtgc accaggactg gctgaacggc aaggagtaca agtgcaaggt ctccaacaaa 1020
ggcctcccag cccccatcga gaaaaccatc tccaaaacca aagggcagcc ccgagaacca 1080
caggtgtaca ccctgccccc atcccgggag gagatgacca agaaccaggt cagcctgacc 1140
tgcctggtca aaggcttcta ccccagcgac atcgccgtgg agtgggagag caatgggcag 1200
ccggagaaca actacaagac cacacctccc atgctggact ccgacggctc cttcttcctc 1260
tacagcaagc tcaccgtgga caagagcagg tggcagcagg ggaacgtctt ctcatgctcc 1320
gtgatgcatg aggctctgca caaccactac acgcagaaga gcctctccct gtctccgggt 1380
aaatga 1386
<210> 578
<211> 1386
<212> DNA
<213> 智人
<400> 578
atggcttggg tgtggacctt gccattcctg atggcagctg cccaaagtgt ccaggcccag 60
gtgcagctgg tcgagagcgg cggagggctg gtgcagcctg gcggcagcct gagactgagc 120
tgcgccgcca gcggcttcac cttcagaagc cactggctgt cctgggtgcg gcaggcccct 180
ggcaagggcc tggaatgggt gtccgtgacc acccaccagg gctacaccta ctacgccgac 240
agcgtgaagg gccggttcac catcagccgg gacaacagca agaacaccct gtacctgcag 300
atgaacagcc tgcgggccga ggacaccgcc gtgtactact gcgccaggga cacctacctg 360
cacttcgact actggggcca gggcaccctg gtcaccgtct cctcagcttc caccaagggc 420
ccatccgtct tccccctggc gccctgctcc aggagcacct ccgagagcac agcggccctg 480
ggctgcctgg tcaaggacta cttccccgaa ccggtgacgg tgtcgtggaa ctcaggcgct 540
ctgaccagcg gcgtgcacac cttcccagct gtcctacagt cctcaggact ctactccctc 600
agcagcgtgg tgacagtgcc ctccagcaac ttcggcaccc agacctacac ctgcaacgta 660
gatcacaagc ccagcaacac caaggtggac aagacagttg agcgcaaatg ttgtgtcgag 720
tgcccaccgt gcccagcacc acctgtggca ggaccgtcag tcttcctctt ccccccaaaa 780
cccaaggaca ccctcatgat ctcccggacc cctgaggtca cgtgcgtggt ggtggacgtg 840
agccacgaag accccgaggt ccagttcaac tggtacgtgg acggcgtgga ggtgcataat 900
gccaagacaa agccacggga ggagcagttc aacagcacgt tccgtgtggt cagcgtcctc 960
accgttgtgc accaggactg gctgaacggc aaggagtaca agtgcaaggt ctccaacaaa 1020
ggcctcccag cccccatcga gaaaaccatc tccaaaacca aagggcagcc ccgagaacca 1080
caggtgtaca ccctgccccc atcccgggag gagatgacca agaaccaggt cagcctgacc 1140
tgcctggtca aaggcttcta ccccagcgac atcgccgtgg agtgggagag caatgggcag 1200
ccggagaaca actacaagac cacacctccc atgctggact ccgacggctc cttcttcctc 1260
tacagcaagc tcaccgtgga caagagcagg tggcagcagg ggaacgtctt ctcatgctcc 1320
gtgatgcatg aggctctgca caaccactac acgcagaaga gcctctccct gtctccgggt 1380
aaatga 1386
<210> 579
<211> 1386
<212> DNA
<213> 智人
<400> 579
atggcttggg tgtggacctt gccattcctg atggcagctg cccaaagtgt ccaggcccag 60
gtgcagctgg tcgagagcgg cggagggctg gtgcagcctg gcggcagcct gagactgagc 120
tgcgccgcca gcggcttcac cttcagaagc cactggctgt cctgggtgcg gcaggcccct 180
ggcaagggcc tggaatgggt gtccgccacc aacagatacg gctacaccta ctacgccgac 240
agcgtgaagg gccggttcac catcagccgg gacaacagca agaacaccct gtacctgcag 300
atgaacagcc tgcgggccga ggacaccgcc gtgtactact gcgccaggga cacctacctg 360
cacttcgact actggggcca gggcaccctg gtcaccgtct cctcagcttc caccaagggc 420
ccatccgtct tccccctggc gccctgctcc aggagcacct ccgagagcac agcggccctg 480
ggctgcctgg tcaaggacta cttccccgaa ccggtgacgg tgtcgtggaa ctcaggcgct 540
ctgaccagcg gcgtgcacac cttcccagct gtcctacagt cctcaggact ctactccctc 600
agcagcgtgg tgacagtgcc ctccagcaac ttcggcaccc agacctacac ctgcaacgta 660
gatcacaagc ccagcaacac caaggtggac aagacagttg agcgcaaatg ttgtgtcgag 720
tgcccaccgt gcccagcacc acctgtggca ggaccgtcag tcttcctctt ccccccaaaa 780
cccaaggaca ccctcatgat ctcccggacc cctgaggtca cgtgcgtggt ggtggacgtg 840
agccacgaag accccgaggt ccagttcaac tggtacgtgg acggcgtgga ggtgcataat 900
gccaagacaa agccacggga ggagcagttc aacagcacgt tccgtgtggt cagcgtcctc 960
accgttgtgc accaggactg gctgaacggc aaggagtaca agtgcaaggt ctccaacaaa 1020
ggcctcccag cccccatcga gaaaaccatc tccaaaacca aagggcagcc ccgagaacca 1080
caggtgtaca ccctgccccc atcccgggag gagatgacca agaaccaggt cagcctgacc 1140
tgcctggtca aaggcttcta ccccagcgac atcgccgtgg agtgggagag caatgggcag 1200
ccggagaaca actacaagac cacacctccc atgctggact ccgacggctc cttcttcctc 1260
tacagcaagc tcaccgtgga caagagcagg tggcagcagg ggaacgtctt ctcatgctcc 1320
gtgatgcatg aggctctgca caaccactac acgcagaaga gcctctccct gtctccgggt 1380
aaatga 1386
<210> 580
<211> 1389
<212> DNA
<213> 智人
<400> 580
atggcttggg tgtggacctt gccattcctg atggcagctg cccaaggtgt ccaggcccag 60
gtgcagctgg tcgagagcgg cggagggctg gtgcagcctg gcggcagcct gagactgagc 120
tgcgccgcca gcggcttcac cttcagaagc cactggctgt cctgggtgcg gcaggcccct 180
ggcaagggcc tggaatgggt gtccaacatc aactacgacg gcagcagcac ctactacgcc 240
gacagcgtga agggccggtt caccatcagc cgggacaaca gcaagaacac cctgtacctg 300
cagatgaaca gcctgcgggc cgaggacacc gccgtgtact actgcgccag ggacacctac 360
ctgcacttcg actactgggg ccagggcacc ctggtcaccg tctcctcagc ttccaccaag 420
ggcccatccg tcttccccct ggcgccctgc tccaggagca cctccgagag cacagcggcc 480
ctgggctgcc tggtcaagga ctacttcccc gaaccggtga cggtgtcgtg gaactcaggc 540
gctctgacca gcggcgtgca caccttccca gctgtcctac agtcctcagg actctactcc 600
ctcagcagcg tggtgacagt gccctccagc aacttcggca cccagaccta cacctgcaac 660
gtagatcaca agcccagcaa caccaaggtg gacaagacag ttgagcgcaa atgttgtgtc 720
gagtgcccac cgtgcccagc accacctgtg gcaggaccgt cagtcttcct cttcccccca 780
aaacccaagg acaccctcat gatctcccgg acccctgagg tcacgtgcgt ggtggtggac 840
gtgagccacg aagaccccga ggtccagttc aactggtacg tggacggcgt ggaggtgcat 900
aatgccaaga caaagccacg ggaggagcag ttcaacagca cgttccgtgt ggtcagcgtc 960
ctcaccgttg tgcaccagga ctggctgaac ggcaaggagt acaagtgcaa ggtctccaac 1020
aaaggcctcc cagcccccat cgagaaaacc atctccaaaa ccaaagggca gccccgagaa 1080
ccacaggtgt acaccctgcc cccatcccgg gaggagatga ccaagaacca ggtcagcctg 1140
acctgcctgg tcaaaggctt ctaccccagc gacatcgccg tggagtggga gagcaatggg 1200
cagccggaga acaactacaa gaccacacct cccatgctgg actccgacgg ctccttcttc 1260
ctctacagca agctcaccgt ggacaagagc aggtggcagc aggggaacgt cttctcatgc 1320
tccgtgatgc atgaggctct gcacaaccac tacacgcaga agagcctctc cctgtctccg 1380
ggtaaatga 1389
<210> 581
<211> 1386
<212> DNA
<213> 智人
<400> 581
atggcttggg tgtggacctt gccattcctg atggcagctg cccaaagtgt ccaggcccag 60
gtgcagctgg tcgagagcgg cggagggctg gtgcagcctg gcggcagcct gagactgagc 120
tgcgccgcca gcggcttcac cttcagaagc cactggctgt cctgggtgcg gcaggcccct 180
ggcaagggcc tggaatgggt gtccgtgatc accccctacg gcgacaccta ctacgccgac 240
agcgtgaagg gccggttcac catcagccgg gacaacagca agaacaccct gtacctgcag 300
atgaacagcc tgcgggccga ggacaccgcc gtgtactact gcgccaggga cacctacctg 360
cacttcgact actggggcca gggcaccctg gtcaccgtct cctcagcttc caccaagggc 420
ccatccgtct tccccctggc gccctgctcc aggagcacct ccgagagcac agcggccctg 480
ggctgcctgg tcaaggacta cttccccgaa ccggtgacgg tgtcgtggaa ctcaggcgct 540
ctgaccagcg gcgtgcacac cttcccagct gtcctacagt cctcaggact ctactccctc 600
agcagcgtgg tgacagtgcc ctccagcaac ttcggcaccc agacctacac ctgcaacgta 660
gatcacaagc ccagcaacac caaggtggac aagacagttg agcgcaaatg ttgtgtcgag 720
tgcccaccgt gcccagcacc acctgtggca ggaccgtcag tcttcctctt ccccccaaaa 780
cccaaggaca ccctcatgat ctcccggacc cctgaggtca cgtgcgtggt ggtggacgtg 840
agccacgaag accccgaggt ccagttcaac tggtacgtgg acggcgtgga ggtgcataat 900
gccaagacaa agccacggga ggagcagttc aacagcacgt tccgtgtggt cagcgtcctc 960
accgttgtgc accaggactg gctgaacggc aaggagtaca agtgcaaggt ctccaacaaa 1020
ggcctcccag cccccatcga gaaaaccatc tccaaaacca aagggcagcc ccgagaacca 1080
caggtgtaca ccctgccccc atcccgggag gagatgacca agaaccaggt cagcctgacc 1140
tgcctggtca aaggcttcta ccccagcgac atcgccgtgg agtgggagag caatgggcag 1200
ccggagaaca actacaagac cacacctccc atgctggact ccgacggctc cttcttcctc 1260
tacagcaagc tcaccgtgga caagagcagg tggcagcagg ggaacgtctt ctcatgctcc 1320
gtgatgcatg aggctctgca caaccactac acgcagaaga gcctctccct gtctccgggt 1380
aaatga 1386
<210> 582
<211> 1386
<212> DNA
<213> 智人
<400> 582
atggcttggg tgtggacctt gccattcctg atggcagctg cccaaagtgt ccaggcccag 60
gtgcagctgg tcgagagcgg cggagggctg gtgcagcctg gcggcagcct gagactgagc 120
tgcgccgcca gcggcttcac cttcagaagc cactggctgt cctgggtgcg gcaggcccct 180
ggcaagggcc tggaatgggt gtccgtgatc accccctacg gcgacaccta ctacgccgac 240
agcgtgaagg gccggttcac catcagccgg gacaacagca agaacaccct gtacctgcag 300
atgaacagcc tgcgggccga ggacaccgcc gtgtactact gcgccaggga cacctacctg 360
cacttcgact actggggcca gggcaccctg gtcaccgtct cctcagcttc caccaagggc 420
ccatccgtct tccccctggc gccctgctcc aggagcacct ccgagagcac agcggccctg 480
ggctgcctgg tcaaggacta cttccccgaa ccggtgacgg tgtcgtggaa ctcaggcgct 540
ctgaccagcg gcgtgcacac cttcccagct gtcctacagt cctcaggact ctactccctc 600
agcagcgtgg tgacagtgcc ctccagcaac ttcggcaccc agacctacac ctgcaacgta 660
gatcacaagc ccagcaacac caaggtggac aagacagttg agcgcaaatg ttgtgtcgag 720
tgcccaccgt gcccagcacc acctgtggca ggaccgtcag tcttcctctt ccccccaaaa 780
cccaaggaca ccctcatgat ctcccggacc cctgaggtca cgtgcgtggt ggtggacgtg 840
agccacgaag accccgaggt ccagttcaac tggtacgtgg acggcgtgga ggtgcataat 900
gccaagacaa agccacggga ggagcagttc aacagcacgt tccgtgtggt cagcgtcctc 960
accgttgtgc accaggactg gctgaacggc aaggagtaca agtgcaaggt ctccaacaaa 1020
ggcctcccag cccccatcga gaaaaccatc tccaaaacca aagggcagcc ccgagaacca 1080
caggtgtaca ccctgccccc atcccgggag gagatgacca agaaccaggt cagcctgacc 1140
tgcctggtca aaggcttcta ccccagcgac atcgccgtgg agtgggagag caatgggcag 1200
ccggagaaca actacaagac cacacctccc atgctggact ccgacggctc cttcttcctc 1260
tacagcaagc tcaccgtgga caagagcagg tggcagcagg ggaacgtctt ctcatgctcc 1320
gtgatgcatg aggctctgca caaccactac acgcagaaga gcctctccct gtctccgggt 1380
aaatga 1386
<210> 583
<211> 393
<212> DNA
<213> 智人
<400> 583
atgaaaaaga cagctatcgc gattgcagtg gcactggctg gtttcgctac cgtagcgcag 60
gccgatatcg aactgaccca gccgccttca gtgagcgttg caccaggtca gaccgcgcgt 120
atctcgtgta gcggcgataa tattggttct ttttatgttc attggtacca gcagaaaccc 180
gggcaggcgc cagttcttgt gatttatgat gataataatc gtccctcagg catcccggaa 240
cgctttagcg gatccaacag cggcaacacc gcgaccctga ccattagcgg cactcaggcg 300
gaagacgaag cggattatta ttgcggttct tgggctggtt cttctggttc ttatgtgttt 360
ggcggccgca cgaagttaac cgttcttggc cag 393
<210> 584
<211> 714
<212> DNA
<213> 智人
<400> 584
atgagtgtgc tcactcaggt cctggcgttg ctgctgctgt ggcttacagg tacgcgttgc 60
gacatcgccc tgacccagcc cgccagcgtg agcggcagcc ctggccagag catcaccatc 120
agctgcaccg gcaccagcag cgacgtgggc gacatcaacg acgtgagctg gtatcagcag 180
caccccggca aggcccccaa gctgatgatc tacgacgtga acaaccggcc cagcggcgtg 240
agcaaccggt tcagcggcag caagagcggc aacaccgcca gcctgaccat cagcggcctc 300
caggccgagg acgaggccga ctactactgc agcagctacg gcgagagcct gaccagctac 360
gtgtttggcg gcggaaccaa gcttaccgtc ctaggtcagc ccaaggctgc cccctcggtc 420
actctgttcc cgccctcctc tgaggagctt caagccaaca aggccacact ggtgtgtctc 480
ataagtgact tctacccggg agccgtgaca gtggcctgga aggcagatag cagccccgtc 540
aaggcgggag tggagacaac cacaccctcc aaacaaagca acaacaagta cgcggccagc 600
agctatctga gcctgacgcc tgagcagtgg aagtcccaca gaagctacag ctgccaggtc 660
acgcatgaag ggagcaccgt ggaaaagaca gtggccccta cagaatgttc atag 714
<210> 585
<211> 705
<212> DNA
<213> 智人
<400> 585
atgagtgtgc tcactcaggt cctggcgttg ctgctgctgt ggcttacagg tacgcgttgc 60
gacatcgagc tgacccagcc ccccagcgtg agcgtggccc ctggccagac cgcccggatc 120
agctgcagcg gcgacaacat cggcagcttc tacgtgcact ggtatcagca gaagcccggc 180
caggcccccg tgctggtgat ctacgacgac aacaaccggc ccagcggcat ccccgagcgg 240
ttcagcggca gcaacagcgg caacaccgcc accctgacca tcagcggcac ccaggccgag 300
gacgaggccg actactactg cgccagctgg accggcgtgg agcccgacta cgtgtttggc 360
ggcggaacaa agcttaccgt cctaggtcag cccaaggctg ccccctcggt cactctgttc 420
ccgccctcct ctgaggagct tcaagccaac aaggccacac tggtgtgtct cataagtgac 480
ttctacccgg gagccgtgac agtggcctgg aaggcagata gcagccccgt caaggcggga 540
gtggagacaa ccacaccctc caaacaaagc aacaacaagt acgcggccag cagctatctg 600
agcctgacgc ctgagcagtg gaagtcccac agaagctaca gctgccaggt cacgcatgaa 660
gggagcaccg tggaaaagac agtggcccct acagaatgtt catag 705
<210> 586
<211> 714
<212> DNA
<213> 智人
<400> 586
atgagtgtgc tcactcaggt cctggcgttg ctgctgctgt ggcttacagg tacgcgttgc 60
gacatcgccc tgacccagcc cgccagcgtg agcggcagcc ctggccagag catcaccatc 120
agctgcaccg gcaccagcag cgacgtgggc gacatcaacg acgtgagctg gtatcagcag 180
caccccggca aggcccccaa gctgatgatc tacgacgtga acaaccggcc cagcggcgtg 240
agcaaccggt tcagcggcag caagagcggc aacaccgcca gcctgaccat cagcggcctc 300
caggccgagg acgaggccga ctactactgc cagagctacg ccggcagcta cctgagcgag 360
gtgttcggcg gagggaccaa gcttaccgtc ctaggtcagc ccaaggctgc cccctcggtc 420
actctgttcc cgccctcctc tgaggagctt caagccaaca aggccacact ggtgtgtctc 480
ataagtgact tctacccggg agccgtgaca gtggcctgga aggcagatag cagccccgtc 540
aaggcgggag tggagacaac cacaccctcc aaacaaagca acaacaagta cgcggccagc 600
agctatctga gcctgacgcc tgagcagtgg aagtcccaca gaagctacag ctgccaggtc 660
acgcatgaag ggagcaccgt ggaaaagaca gtggccccta cagaatgttc atag 714
<210> 587
<211> 714
<212> DNA
<213> 智人
<400> 587
atgagtgtgc tcactcaggt cctggcgttg ctgctgctgt ggcttacagg tacgcgttgc 60
gacatcgccc tgacccagcc cgccagcgtg agcggcagcc ctggccagag catcaccatc 120
agctgcaccg gcaccagcag cgacgtgggc gacatcaacg acgtgagctg gtatcagcag 180
caccccggca aggcccccaa gctgatgatc tacgacgtga acaaccggcc cagcggcgtg 240
agcaaccggt tcagcggcag caagagcggc aacaccgcca gcctgaccat cagcggcctc 300
caggccgagg acgaggccga ctactactgc agcagctacg gcgagagcct gaccagctac 360
gtgtttggcg gcggaaccaa gcttaccgtc ctaggtcagc ccaaggctgc cccctcggtc 420
actctgttcc cgccctcctc tgaggagctt caagccaaca aggccacact ggtgtgtctc 480
ataagtgact tctacccggg agccgtgaca gtggcctgga aggcagatag cagccccgtc 540
aaggcgggag tggagacaac cacaccctcc aaacaaagca acaacaagta cgcggccagc 600
agctatctga gcctgacgcc tgagcagtgg aagtcccaca gaagctacag ctgccaggtc 660
acgcatgaag ggagcaccgt ggaaaagaca gtggccccta cagaatgttc atag 714
<210> 588
<211> 714
<212> DNA
<213> 智人
<400> 588
atgagtgtgc tcactcaggt cctggcgttg ctgctgctgt ggcttacagg tacgcgttgc 60
gacatcgccc tgacccagcc cgccagcgtg agcggcagcc ctggccagag catcaccatc 120
agctgcaccg gcaccagcag cgacgtgggc gacatcaacg acgtgagctg gtatcagcag 180
caccccggca aggcccccaa gctgatgatc tacgacgtga acaaccggcc cagcggcgtg 240
agcaaccggt tcagcggcag caagagcggc aacaccgcca gcctgaccat cagcggcctc 300
caggccgagg acgaggccga ctactactgc agcagctacg gcgagagcct gaccagctac 360
gtgtttggcg gcggaaccaa gcttaccgtc ctaggtcagc ccaaggctgc cccctcggtc 420
actctgttcc cgccctcctc tgaggagctt caagccaaca aggccacact ggtgtgtctc 480
ataagtgact tctacccggg agccgtgaca gtggcctgga aggcagatag cagccccgtc 540
aaggcgggag tggagacaac cacaccctcc aaacaaagca acaacaagta cgcggccagc 600
agctatctga gcctgacgcc tgagcagtgg aagtcccaca gaagctacag ctgccaggtc 660
acgcatgaag ggagcaccgt ggaaaagaca gtggccccta cagaatgttc atag 714
<210> 589
<211> 714
<212> DNA
<213> 智人
<400> 589
atgagtgtgc tcactcaggt cctggcgttg ctgctgctgt ggcttacagg tacgcgttgc 60
gacatcgccc tgacccagcc cgccagcgtg agcggcagcc ctggccagag catcaccatc 120
agctgcaccg gcaccagcag cgacgtgggc gacatcaacg acgtgagctg gtatcagcag 180
caccccggca aggcccccaa gctgatgatc tacgacgtga acaaccggcc cagcggcgtg 240
agcaaccggt tcagcggcag caagagcggc aacaccgcca gcctgaccat cagcggcctc 300
caggccgagg acgaggccga ctactactgc agcagctacg gcgagagcct gaccagctac 360
gtgtttggcg gcggaaccaa gcttaccgtc ctaggtcagc ccaaggctgc cccctcggtc 420
actctgttcc cgccctcctc tgaggagctt caagccaaca aggccacact ggtgtgtctc 480
ataagtgact tctacccggg agccgtgaca gtggcctgga aggcagatag cagccccgtc 540
aaggcgggag tggagacaac cacaccctcc aaacaaagca acaacaagta cgcggccagc 600
agctatctga gcctgacgcc tgagcagtgg aagtcccaca gaagctacag ctgccaggtc 660
acgcatgaag ggagcaccgt ggaaaagaca gtggccccta cagaatgttc atag 714
<210> 590
<211> 714
<212> DNA
<213> 智人
<400> 590
atgagtgtgc tcactcaggt cctggcgttg ctgctgctgt ggcttacagg tacgcgttgc 60
gacatcgccc tgacccagcc cgccagcgtg agcggcagcc ctggccagag catcaccatc 120
agctgcaccg gcaccagcag cgacgtgggc gacatcaacg acgtgagctg gtatcagcag 180
caccccggca aggcccccaa gctgatgatc tacgacgtga acaaccggcc cagcggcgtg 240
agcaaccggt tcagcggcag caagagcggc aacaccgcca gcctgaccat cagcggcctc 300
caggccgagg acgaggccga ctactactgc agcagctacg gcgagagcct gaccagctac 360
gtgtttggcg gcggaaccaa gcttaccgtc ctaggtcagc ccaaggctgc cccctcggtc 420
actctgttcc cgccctcctc tgaggagctt caagccaaca aggccacact ggtgtgtctc 480
ataagtgact tctacccggg agccgtgaca gtggcctgga aggcagatag cagccccgtc 540
aaggcgggag tggagacaac cacaccctcc aaacaaagca acaacaagta cgcggccagc 600
agctatctga gcctgacgcc tgagcagtgg aagtcccaca gaagctacag ctgccaggtc 660
acgcatgaag ggagcaccgt ggaaaagaca gtggccccta cagaatgttc atag 714
<210> 591
<211> 714
<212> DNA
<213> 智人
<400> 591
atgagtgtgc tcactcaggt cctggcgttg ctgctgctgt ggcttacagg tacgcgttgc 60
gacatcgccc tgacccagcc cgccagcgtg agcggcagcc ctggccagag catcaccatc 120
agctgcaccg gcaccagcag cgacgtgggc gacatcaacg acgtgagctg gtatcagcag 180
caccccggca aggcccccaa gctgatgatc tacgacgtga acaaccggcc cagcggcgtg 240
agcaaccggt tcagcggcag caagagcggc aacaccgcca gcctgaccat cagcggcctc 300
caggccgagg acgaggccga ctactactgc agcacctacg acggccctgg cctgagcgag 360
gtgttcggcg gagggaccaa gcttaccgtc ctaggtcagc ccaaggctgc cccctcggtc 420
actctgttcc cgccctcctc tgaggagctt caagccaaca aggccacact ggtgtgtctc 480
ataagtgact tctacccggg agccgtgaca gtggcctgga aggcagatag cagccccgtc 540
aaggcgggag tggagacaac cacaccctcc aaacaaagca acaacaagta cgcggccagc 600
agctatctga gcctgacgcc tgagcagtgg aagtcccaca gaagctacag ctgccaggtc 660
acgcatgaag ggagcaccgt ggaaaagaca gtggccccta cagaatgttc atag 714
<210> 592
<211> 714
<212> DNA
<213> 智人
<400> 592
atgagtgtgc tcactcaggt cctggcgttg ctgctgctgt ggcttacagg tacgcgttgc 60
gacatcgccc tgacccagcc cgccagcgtg agcggcagcc ctggccagag catcaccatc 120
agctgcaccg gcaccagcag cgacgtgggc gacatcaacg acgtgagctg gtatcagcag 180
caccccggca aggcccccaa gctgatgatc tacgacgtga acaaccggcc cagcggcgtg 240
agcaaccggt tcagcggcag caagagcggc aacaccgcca gcctgaccat cagcggcctc 300
caggccgagg acgaggccga ctactactgc agcacctacg acggccctgg cctgagcgag 360
gtgttcggcg gagggaccaa gcttaccgtc ctaggtcagc ccaaggctgc cccctcggtc 420
actctgttcc cgccctcctc tgaggagctt caagccaaca aggccacact ggtgtgtctc 480
ataagtgact tctacccggg agccgtgaca gtggcctgga aggcagatag cagccccgtc 540
aaggcgggag tggagacaac cacaccctcc aaacaaagca acaacaagta cgcggccagc 600
agctatctga gcctgacgcc tgagcagtgg aagtcccaca gaagctacag ctgccaggtc 660
acgcatgaag ggagcaccgt ggaaaagaca gtggccccta cagaatgttc atag 714
<210> 593
<211> 714
<212> DNA
<213> 智人
<400> 593
atgagtgtgc tcactcaggt cctggcgttg ctgctgctgt ggcttacagg tacgcgttgc 60
gacatcgccc tgacccagcc cgccagcgtg agcggcagcc ctggccagag catcaccatc 120
agctgcaccg gcaccagcag cgacgtgggc gacatcaacg acgtgagctg gtatcagcag 180
caccccggca aggcccccaa gctgatgatc tacgacgtga acaaccggcc cagcggcgtg 240
agcaaccggt tcagcggcag caagagcggc aacaccgcca gcctgaccat cagcggcctc 300
caggccgagg acgaggccga ctactactgc agcacctacg acggccctgg cctgagcgag 360
gtgttcggcg gagggaccaa gcttaccgtc ctaggtcagc ccaaggctgc cccctcggtc 420
actctgttcc cgccctcctc tgaggagctt caagccaaca aggccacact ggtgtgtctc 480
ataagtgact tctacccggg agccgtgaca gtggcctgga aggcagatag cagccccgtc 540
aaggcgggag tggagacaac cacaccctcc aaacaaagca acaacaagta cgcggccagc 600
agctatctga gcctgacgcc tgagcagtgg aagtcccaca gaagctacag ctgccaggtc 660
acgcatgaag ggagcaccgt ggaaaagaca gtggccccta cagaatgttc atag 714
<210> 594
<211> 213
<212> PRT
<213> 智人
<400> 594
Met Gln Leu Pro Leu Ala Leu Cys Leu Val Cys Leu Leu Val His Thr
1 5 10 15
Ala Phe Arg Val Val Glu Gly Gln Gly Trp Gln Ala Phe Lys Asn Asp
20 25 30
Ala Thr Glu Ile Ile Pro Glu Leu Gly Glu Tyr Pro Glu Pro Pro Pro
35 40 45
Glu Leu Glu Asn Asn Lys Thr Met Asn Arg Ala Glu Asn Gly Gly Arg
50 55 60
Pro Pro His His Pro Phe Glu Thr Lys Asp Val Ser Glu Tyr Ser Cys
65 70 75 80
Arg Glu Leu His Phe Thr Arg Tyr Val Thr Asp Gly Pro Cys Arg Ser
85 90 95
Ala Lys Pro Val Thr Glu Leu Val Cys Ser Gly Gln Cys Gly Pro Ala
100 105 110
Arg Leu Leu Pro Asn Ala Ile Gly Arg Gly Lys Trp Trp Arg Pro Ser
115 120 125
Gly Pro Asp Phe Arg Cys Ile Pro Asp Arg Tyr Arg Ala Gln Arg Val
130 135 140
Gln Leu Leu Cys Pro Gly Gly Glu Ala Pro Arg Ala Arg Lys Val Arg
145 150 155 160
Leu Val Ala Ser Cys Lys Cys Lys Arg Leu Thr Arg Phe His Asn Gln
165 170 175
Ser Glu Leu Lys Asp Phe Gly Thr Glu Ala Ala Arg Pro Gln Lys Gly
180 185 190
Arg Lys Pro Arg Pro Arg Ala Arg Ser Ala Lys Ala Asn Gln Ala Glu
195 200 205
Leu Glu Asn Ala Tyr
210
<210> 595
<211> 14
<212> PRT
<213> 智人
<400> 595
Ala Arg Leu Leu Asn Ala Ile Gly Arg Gly Lys Trp Trp Arg
1 5 10
<210> 596
<211> 15
<212> PRT
<213> 智人
<400> 596
Arg Leu Val Ala Ser Cys Lys Cys Lys Arg Leu Thr Arg Phe His
1 5 10 15
<210> 597
<211> 13
<212> PRT
<213> 智人
<400> 597
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
1 5 10
<210> 598
<211> 19
<212> PRT
<213> 智人
<400> 598
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
1 5 10 15
Gly Gly Gly
<210> 599
<211> 21
<212> DNA
<213> 人工
<220>
<223> siRNA
<400> 599
taaattatca taaagtccta a 21
<210> 600
<211> 21
<212> DNA
<213> 人工
<220>
<223> siRNA
<400> 600
aggactttat gataatttat t 21
<210> 601
<211> 21
<212> DNA
<213> 人工
<220>
<223> siRNA
<400> 601
atagtggtta aataactcca g 21
<210> 602
<211> 21
<212> DNA
<213> 人工
<220>
<223> siRNA
<400> 602
ggagttattt aaccactatt t 21
<210> 603
<211> 21
<212> DNA
<213> 人工
<220>
<223> siRNA
<400> 603
taaattctcg tgatgtgcca t 21
<210> 604
<211> 21
<212> DNA
<213> 人工
<220>
<223> siRNA
<400> 604
ggcacatcac gagaatttat t 21
<210> 605
<211> 21
<212> DNA
<213> 人工
<220>
<223> siRNA
<400> 605
tttcttatag cacagctggt t 21
<210> 606
<211> 21
<212> DNA
<213> 人工
<220>
<223> siRNA
<400> 606
ccagctgtgc tataagaaat t 21
<210> 607
<211> 21
<212> DNA
<213> 人工
<220>
<223> siRNA
<400> 607
tagacctttc catccacgct g 21
<210> 608
<211> 21
<212> DNA
<213> 人工
<220>
<223> siRNA
<400> 608
gcgtggatgg aaaggtctat t 21
<210> 609
<211> 29
<212> DNA
<213> 人工
<220>
<223> siRNA
<400> 609
atgcagctcc cactggccct gtgtcttgt 29
<210> 610
<211> 30
<212> DNA
<213> 人工
<220>
<223> siRNA
<400> 610
aatcaggccg agctggagaa cgcctactag 30
<210> 611
<211> 102
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体
<220>
<221> misc_feature
<222> (31)..(35)
<223> CDR
<220>
<221> misc_feature
<222> (31)..(35)
<223> aa为任何氨基酸
<220>
<221> misc_feature
<222> (50)..(54)
<223> CDR
<220>
<221> misc_feature
<222> (50)..(54)
<223> Xaa为任何氨基酸
<220>
<221> misc_feature
<222> (87)..(91)
<223> CDR
<220>
<221> misc_feature
<222> (87)..(91)
<223> Xaa为任何氨基酸
<400> 611
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 Ile Pro Phe Ser Xaa Xaa
20 25 30
Xaa Xaa Xaa Trp Phe Arg Gln Ala Pro Gly Lys Gln Arg Asp Ser Val
35 40 45
Ala Xaa Xaa Xaa Xaa Xaa Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys
50 55 60
Asn Thr Val Tyr Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala
65 70 75 80
Val Tyr Arg Cys Tyr Phe Xaa Xaa Xaa Xaa Xaa Trp Gly Gln Gly Thr
85 90 95
Gln Val Thr Val Ser Ser
100
<210> 612
<211> 102
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体
<220>
<221> misc_feature
<222> (31)..(35)
<223> CDR
<220>
<221> misc_feature
<222> (31)..(35)
<223> Xaa为任何氨基酸
<220>
<221> misc_feature
<222> (50)..(54)
<223> CDR
<220>
<221> misc_feature
<222> (50)..(54)
<223> Xaa为任何氨基酸
<220>
<221> misc_feature
<222> (87)..(91)
<223> CDR
<220>
<221> misc_feature
<222> (87)..(91)
<223> Xaa为任何氨基酸
<400> 612
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Val Gly Ser Gly Arg Thr Phe Ser Xaa Xaa
20 25 30
Xaa Xaa Xaa Trp Phe Arg Leu Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ala Xaa Xaa Xaa Xaa Xaa Arg Phe Thr Ile Ser Arg Asp Thr Ala Ser
50 55 60
Asn Arg Gly Tyr Leu His Met Asn Asn Leu Thr Pro Glu Asp Thr Ala
65 70 75 80
Val Tyr Tyr Cys Ala Ala Xaa Xaa Xaa Xaa Xaa Trp Gly Gln Gly Thr
85 90 95
Gln Val Thr Val Ser Ser
100
<210> 613
<211> 102
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体
<220>
<221> misc_feature
<222> (31)..(35)
<223> CDR
<220>
<221> misc_feature
<222> (31)..(35)
<223> Xaa为任何氨基酸
<220>
<221> misc_feature
<222> (50)..(54)
<223> CDR
<220>
<221> misc_feature
<222> (50)..(54)
<223> Xaa为任何氨基酸
<220>
<221> misc_feature
<222> (87)..(91)
<223> CDR
<220>
<221> misc_feature
<222> (87)..(91)
<223> Xaa为任何氨基酸
<400> 613
Ala Val Gln Leu Val Asp Ser Gly Gly Gly Leu Val Gln Ala Gly Asp
1 5 10 15
Ser Leu Lys Leu Ser Cys Ala Leu Thr Gly Gly Ala Phe Thr Xaa Xaa
20 25 30
Xaa Xaa Xaa Trp Phe Arg Gln Thr Pro Gly Arg Glu Arg Glu Phe Val
35 40 45
Ala Xaa Xaa Xaa Xaa Xaa Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys
50 55 60
Asn Met Val Tyr Leu Arg Met Asn Ser Leu Ile Pro Glu Asp Ala Ala
65 70 75 80
Val Tyr Ser Cys Ala Ala Xaa Xaa Xaa Xaa Xaa Trp Gly Gln Gly Thr
85 90 95
Leu Val Thr Val Ser Ser
100
<210> 614
<211> 102
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体
<220>
<221> misc_feature
<222> (31)..(35)
<223> CDR
<220>
<221> misc_feature
<222> (31)..(35)
<223> Xaa为任何氨基酸
<220>
<221> misc_feature
<222> (50)..(54)
<223> CDR
<220>
<221> misc_feature
<222> (50)..(54)
<223> Xaa为任何氨基酸
<220>
<221> misc_feature
<222> (87)..(91)
<223> CDR
<220>
<221> misc_feature
<222> (87)..(91)
<223> Xaa为任何氨基酸
<400> 614
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Glu Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Thr Ala Ser Glu Ser Pro Phe Arg Xaa Xaa
20 25 30
Xaa Xaa Xaa Trp Phe Arg Gln Thr Ser Gly Gln Glu Arg Glu Phe Val
35 40 45
Ala Xaa Xaa Xaa Xaa Xaa Arg Phe Thr Ile Ser Arg Asp Asp Ala Lys
50 55 60
Asn Thr Val Trp Leu His Gly Ser Thr Leu Lys Pro Glu Asp Thr Ala
65 70 75 80
Val Tyr Tyr Cys Ala Ala Xaa Xaa Xaa Xaa Xaa Trp Gly Gln Gly Thr
85 90 95
Gln Val Thr Val Ser Ser
100
<210> 615
<211> 102
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体
<220>
<221> misc_feature
<222> (31)..(35)
<223> CDR
<220>
<221> misc_feature
<222> (31)..(35)
<223> Xaa为任何氨基酸
<220>
<221> misc_feature
<222> (50)..(54)
<223> CDR
<220>
<221> misc_feature
<222> (50)..(54)
<223> Xaa为任何氨基酸
<220>
<221> misc_feature
<222> (87)..(91)
<223> CDR
<220>
<221> misc_feature
<222> (87)..(91)
<223> Xaa为任何氨基酸
<400> 615
Ala Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Gly Gly Gly
1 5 10 15
Ser Leu Arg Leu Ala Cys Ala Ala Ser Glu Arg Ile Phe Asp Xaa Xaa
20 25 30
Xaa Xaa Xaa Trp Tyr Arg Gln Gly Pro Gly Asn Glu Arg Glu Leu Val
35 40 45
Ala Xaa Xaa Xaa Xaa Xaa Arg Phe Thr Ile Ser Met Asp Tyr Thr Lys
50 55 60
Gln Thr Val Tyr Leu His Met Asn Ser Leu Arg Pro Glu Asp Thr Gly
65 70 75 80
Leu Tyr Tyr Cys Lys Ile Xaa Xaa Xaa Xaa Xaa Trp Gly Gln Gly Thr
85 90 95
Gln Val Thr Val Ser Ser
100
<210> 616
<211> 102
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体
<220>
<221> misc_feature
<222> (31)..(35)
<223> CDR
<220>
<221> misc_feature
<222> (31)..(35)
<223> Xaa为任何氨基酸
<220>
<221> misc_feature
<222> (50)..(54)
<223> CDR
<220>
<221> misc_feature
<222> (50)..(54)
<223> Xaa为任何氨基酸
<220>
<221> misc_feature
<222> (87)..(91)
<223> CDR
<220>
<221> misc_feature
<222> (87)..(91)
<223> Xaa为任何氨基酸
<400> 616
Asp Val Lys Phe Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Val Ala Ser Gly Phe Asn Phe Asp Xaa Xaa
20 25 30
Xaa Xaa Xaa Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Glu Val
35 40 45
Ala Xaa Xaa Xaa Xaa Xaa Arg Phe Thr Ile Ser Ser Glu Lys Asp Lys
50 55 60
Asn Ser Val Tyr Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala
65 70 75 80
Leu Tyr Ile Cys Ala Gly Xaa Xaa Xaa Xaa Xaa Trp Gly Arg Gly Thr
85 90 95
Gln Val Thr Val Ser Ser
100
<210> 617
<211> 102
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体
<220>
<221> misc_feature
<222> (31)..(35)
<223> CDR
<220>
<221> misc_feature
<222> (31)..(35)
<223> Xaa为任何氨基酸
<220>
<221> misc_feature
<222> (50)..(54)
<223> CDR
<220>
<221> misc_feature
<222> (50)..(54)
<223> Xaa为任何氨基酸
<220>
<221> misc_feature
<222> (87)..(91)
<223> CDR
<220>
<221> misc_feature
<222> (87)..(91)
<223> Xaa为任何氨基酸
<400> 617
Gln Val Arg Leu Ala Glu Ser Gly Gly Gly Leu Val Gln Ser Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Val Ala Ser Gly Ser Thr Tyr Thr Xaa Xaa
20 25 30
Xaa Xaa Xaa Trp Tyr Arg Gln Tyr Pro Gly Lys Gln Arg Ala Leu Val
35 40 45
Ala Xaa Xaa Xaa Xaa Xaa Arg Phe Thr Ile Ala Arg Asp Ser Thr Lys
50 55 60
Asp Thr Phe Cys Leu Gln Met Asn Asn Leu Lys Pro Glu Asp Thr Ala
65 70 75 80
Val Tyr Tyr Cys Tyr Ala Xaa Xaa Xaa Xaa Xaa Trp Gly Gln Gly Thr
85 90 95
Gln Val Thr Val Ser Ser
100
<210> 618
<211> 102
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体
<220>
<221> misc_feature
<222> (31)..(35)
<223> CDR
<220>
<221> misc_feature
<222> (31)..(35)
<223> Xaa为任何氨基酸
<220>
<221> misc_feature
<222> (50)..(54)
<223> CDR
<220>
<221> misc_feature
<222> (50)..(54)
<223> Xaa为任何氨基酸
<220>
<221> misc_feature
<222> (87)..(91)
<223> CDR
<220>
<221> misc_feature
<222> (87)..(91)
<223> Xaa为任何氨基酸
<400> 618
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Ser Asp Xaa Xaa
20 25 30
Xaa Xaa Xaa Trp Phe Arg Gln Ala Pro Gly Lys Pro Arg Glu Gly Val
35 40 45
Ser Xaa Xaa Xaa Xaa Xaa Arg Phe Thr Ile Ser Thr Asp Asn Ala Lys
50 55 60
Asn Thr Val His Leu Leu Met Asn Arg Val Asn Ala Glu Asp Thr Ala
65 70 75 80
Leu Tyr Tyr Cys Ala Val Xaa Xaa Xaa Xaa Xaa Trp Gly Arg Gly Thr
85 90 95
Arg Val Thr Val Ser Ser
100
<210> 619
<211> 102
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体
<220>
<221> misc_feature
<222> (31)..(35)
<223> CDR
<220>
<221> misc_feature
<222> (31)..(35)
<223> Xaa为任何氨基酸
<220>
<221> misc_feature
<222> (50)..(54)
<223> CDR
<220>
<221> misc_feature
<222> (50)..(54)
<223> Xaa为任何氨基酸
<220>
<221> misc_feature
<222> (87)..(91)
<223> CDR
<220>
<221> misc_feature
<222> (87)..(91)
<223> Xaa为任何氨基酸
<400> 619
Gln 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 Gln Ala Ser Gly Asp Ile Ser Thr Xaa Xaa
20 25 30
Xaa Xaa Xaa Trp Tyr Arg Gln Val Pro Gly Lys Leu Arg Glu Phe Val
35 40 45
Ala Xaa Xaa Xaa Xaa Xaa Arg Phe Thr Ile Ser Gly Asp Asn Ala Lys
50 55 60
Arg Ala Ile Tyr Leu Gln Met Asn Asn Leu Lys Pro Asp Asp Thr Ala
65 70 75 80
Val Tyr Tyr Cys Asn Arg Xaa Xaa Xaa Xaa Xaa Trp Gly Gln Gly Thr
85 90 95
Gln Val Thr Val Ser Pro
100
<210> 620
<211> 102
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体
<220>
<221> misc_feature
<222> (31)..(35)
<223> CDR
<220>
<221> misc_feature
<222> (31)..(35)
<223> Xaa为任何氨基酸
<220>
<221> misc_feature
<222> (50)..(54)
<223> CDR
<220>
<221> misc_feature
<222> (50)..(54)
<223> Xaa为任何氨基酸
<220>
<221> misc_feature
<222> (87)..(91)
<223> CDR
<220>
<221> misc_feature
<222> (87)..(91)
<223> Xaa为任何氨基酸
<400> 620
Gln Val Pro Val Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Asp
1 5 10 15
Ser Leu Arg Leu Phe Cys Ala Val Pro Ser Phe Thr Ser Thr Xaa Xaa
20 25 30
Xaa Xaa Xaa Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ala Xaa Xaa Xaa Xaa Xaa Arg Phe Thr Ile Ser Arg Asn Ala Thr Lys
50 55 60
Asn Thr Leu Thr Leu Arg Met Asp Ser Leu Lys Pro Glu Asp Thr Ala
65 70 75 80
Val Tyr Tyr Cys Ala Ala Xaa Xaa Xaa Xaa Xaa Trp Gly Gln Gly Thr
85 90 95
Gln Val Thr Val Ser Ser
100
<210> 621
<211> 102
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体
<220>
<221> misc_feature
<222> (31)..(35)
<223> CDR
<220>
<221> misc_feature
<222> (31)..(35)
<223> Xaa为任何氨基酸
<220>
<221> misc_feature
<222> (50)..(54)
<223> CDR
<220>
<221> misc_feature
<222> (50)..(54)
<223> Xaa为任何氨基酸
<220>
<221> misc_feature
<222> (87)..(91)
<223> CDR
<220>
<221> misc_feature
<222> (87)..(91)
<223> Xaa为任何氨基酸
<400> 621
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Asp
1 5 10 15
Ser Leu Arg Leu Phe Cys Thr Val Ser Gly Gly Thr Ala Ser Xaa Xaa
20 25 30
Xaa Xaa Xaa Trp Phe Arg Gln Ala Pro Gly Glu Lys Arg Glu Phe Val
35 40 45
Ala Xaa Xaa Xaa Xaa Xaa Arg Phe Thr Ile Ala Arg Glu Asn Ala Gly
50 55 60
Asn Met Val Tyr Leu Gln Met Asn Asn Leu Lys Pro Asp Asp Thr Ala
65 70 75 80
Leu Tyr Thr Cys Ala Ala Xaa Xaa Xaa Xaa Xaa Trp Gly Arg Gly Thr
85 90 95
Gln Val Thr Val Ser Ser
100
<210> 622
<211> 102
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体
<220>
<221> misc_feature
<222> (31)..(35)
<223> CDR
<220>
<221> misc_feature
<222> (31)..(35)
<223> Xaa为任何氨基酸
<220>
<221> misc_feature
<222> (50)..(54)
<223> CDR
<220>
<221> misc_feature
<222> (50)..(54)
<223> Xaa为任何氨基酸
<220>
<221> misc_feature
<222> (87)..(91)
<223> CDR
<220>
<221> misc_feature
<222> (87)..(91)
<223> Xaa为任何氨基酸
<400> 622
Ala Val Gln Leu Val Glu Ser Gly Gly Asp Ser Val Gln Pro Gly Asp
1 5 10 15
Ser Gln Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Asn Ser Xaa Xaa
20 25 30
Xaa Xaa Xaa Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Val Phe Leu
35 40 45
Ala Xaa Xaa Xaa Xaa Xaa Arg Phe Thr Ile Ser Arg Asp Ser Ala Lys
50 55 60
Asn Met Met Tyr Leu Gln Met Asn Asn Leu Lys Pro Gln Asp Thr Ala
65 70 75 80
Val Tyr Tyr Cys Ala Ala Xaa Xaa Xaa Xaa Xaa Trp Gly Gln Gly Thr
85 90 95
Gln Val Thr Val Ser Ser
100
<210> 623
<211> 102
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体
<220>
<221> misc_feature
<222> (31)..(35)
<223> CDR
<220>
<221> misc_feature
<222> (31)..(35)
<223> Xaa为任何氨基酸
<220>
<221> misc_feature
<222> (50)..(54)
<223> CDR
<220>
<221> misc_feature
<222> (50)..(54)
<223> Xaa为任何氨基酸
<220>
<221> misc_feature
<222> (87)..(91)
<223> CDR
<220>
<221> misc_feature
<222> (87)..(91)
<223> Xaa为任何氨基酸
<400> 623
Ala Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Val Val Ser Gly Leu Thr Ser Ser Xaa Xaa
20 25 30
Xaa Xaa Xaa Trp Phe Arg Gln Thr Pro Trp Gln Glu Arg Asp Phe Val
35 40 45
Ala Xaa Xaa Xaa Xaa Xaa Arg Phe Thr Ile Ser Arg Asp Asn Tyr Lys
50 55 60
Asp Thr Val Leu Leu Glu Met Asn Phe Leu Lys Pro Glu Asp Thr Ala
65 70 75 80
Ile Tyr Tyr Cys Ala Ala Xaa Xaa Xaa Xaa Xaa Trp Gly Gln Gly Thr
85 90 95
Gln Val Thr Val Ser Ser
100
<210> 624
<211> 102
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体
<220>
<221> misc_feature
<222> (31)..(35)
<223> CDR
<220>
<221> misc_feature
<222> (31)..(35)
<223> Xaa为任何氨基酸
<220>
<221> misc_feature
<222> (50)..(54)
<223> CDR
<220>
<221> misc_feature
<222> (50)..(54)
<223> Xaa为任何氨基酸
<220>
<221> misc_feature
<222> (87)..(91)
<223> CDR
<220>
<221> misc_feature
<222> (87)..(91)
<223> Xaa为任何氨基酸
<400> 624
Ala Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Ala
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Thr Ser Thr Arg Thr Leu Asp Xaa Xaa
20 25 30
Xaa Xaa Xaa Trp Phe Arg Gln Ala Pro Gly Arg Asp Arg Glu Phe Val
35 40 45
Ala Xaa Xaa Xaa Xaa Xaa Arg Phe Thr Val Ser Arg Asp Ser Ala Glu
50 55 60
Asn Thr Val Ala Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala
65 70 75 80
Val Tyr Tyr Cys Ala Ala Xaa Xaa Xaa Xaa Xaa Trp Gly Gln Gly Thr
85 90 95
Arg Val Thr Val Ser Ser
100
<210> 625
<211> 102
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体
<220>
<221> misc_feature
<222> (31)..(35)
<223> CDR
<220>
<221> misc_feature
<222> (31)..(35)
<223> Xaa为任何氨基酸
<220>
<221> misc_feature
<222> (50)..(54)
<223> CDR
<220>
<221> misc_feature
<222> (50)..(54)
<223> Xaa为任何氨基酸
<220>
<221> misc_feature
<222> (87)..(91)
<223> CDR
<220>
<221> misc_feature
<222> (87)..(91)
<223> Xaa为任何氨基酸
<400> 625
Gln 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 Thr Val Ser Arg Leu Thr Ala His Xaa Xaa
20 25 30
Xaa Xaa Xaa Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Ala Val
35 40 45
Ser Xaa Xaa Xaa Xaa Xaa Arg Phe Thr Ile Ser Arg Asp Tyr Ala Gly
50 55 60
Asn Thr Ala Phe Leu Gln Met Asp Ser Leu Lys Pro Glu Asp Thr Gly
65 70 75 80
Val Tyr Tyr Cys Ala Thr Xaa Xaa Xaa Xaa Xaa Trp Gly Gln Gly Thr
85 90 95
Gln Val Thr Val Ser Ser
100
<210> 626
<211> 102
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体
<220>
<221> misc_feature
<222> (31)..(35)
<223> CDR
<220>
<221> misc_feature
<222> (31)..(35)
<223> Xaa为任何氨基酸
<220>
<221> misc_feature
<222> (50)..(54)
<223> CDR
<220>
<221> misc_feature
<222> (50)..(54)
<223> Xaa为任何氨基酸
<220>
<221> misc_feature
<222> (87)..(91)
<223> CDR
<220>
<221> misc_feature
<222> (87)..(91)
<223> Xaa为任何氨基酸
<400> 626
Glu Val Gln Leu Val Glu Ser Gly Gly Glu Leu Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Lys Leu Ser Cys Thr Ala Ser Gly Arg Asn Phe Val Xaa Xaa
20 25 30
Xaa Xaa Xaa Trp Phe Arg Arg Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ala Xaa Xaa Xaa Xaa Xaa Arg Phe Thr Val Ser Arg Asp Asn Gly Lys
50 55 60
Asn Thr Ala Tyr Leu Arg Met Asn Ser Leu Lys Pro Glu Asp Thr Ala
65 70 75 80
Asp Tyr Tyr Cys Ala Val Xaa Xaa Xaa Xaa Xaa Leu Gly Ser Gly Thr
85 90 95
Gln Val Thr Val Ser Ser
100
<210> 627
<211> 102
<212> PRT
<213> 人工序列
<220>
<223> GLEW类纳米体
<220>
<221> misc_feature
<222> (31)..(35)
<223> CDR
<220>
<221> misc_feature
<222> (31)..(35)
<223> Xaa为任何氨基酸
<220>
<221> misc_feature
<222> (50)..(54)
<223> CDR
<220>
<221> misc_feature
<222> (50)..(54)
<223> Xaa为任何氨基酸
<220>
<221> misc_feature
<222> (87)..(91)
<223> CDR
<220>
<221> misc_feature
<222> (87)..(91)
<223> Xaa为任何氨基酸
<400> 627
Ala 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 Thr Phe Ser Xaa Xaa
20 25 30
Xaa Xaa Xaa Trp Val Arg Gln Ala Pro Gly Lys Val Leu Glu Trp Val
35 40 45
Ser Xaa Xaa Xaa Xaa Xaa Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys
50 55 60
Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala
65 70 75 80
Val Tyr Tyr Cys Val Lys Xaa Xaa Xaa Xaa Xaa Gly Ser Gln Gly Thr
85 90 95
Gln Val Thr Val Ser Ser
100
<210> 628
<211> 102
<212> PRT
<213> 人工序列
<220>
<223> GLEW类纳米体
<220>
<221> misc_feature
<222> (31)..(35)
<223> CDR
<220>
<221> misc_feature
<222> (31)..(35)
<223> Xaa为任何氨基酸
<220>
<221> misc_feature
<222> (50)..(54)
<223> CDR
<220>
<221> misc_feature
<222> (50)..(54)
<223> Xaa为任何氨基酸
<220>
<221> misc_feature
<222> (87)..(91)
<223> CDR
<220>
<221> misc_feature
<222> (87)..(91)
<223> Xaa为任何氨基酸
<400> 628
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 Val Cys Val Ser Ser Gly Cys Thr Xaa Xaa
20 25 30
Xaa Xaa Xaa Trp Val Arg Gln Ala Pro Gly Lys Ala Glu Glu Trp Val
35 40 45
Ser Xaa Xaa Xaa Xaa Xaa Arg Phe Lys Ile Ser Arg Asp Asn Ala Lys
50 55 60
Lys Thr Leu Tyr Leu Gln Met Asn Ser Leu Gly Pro Glu Asp Thr Ala
65 70 75 80
Met Tyr Tyr Cys Gln Arg Xaa Xaa Xaa Xaa Xaa Arg Gly Gln Gly Thr
85 90 95
Gln Val Thr Val Ser Ser
100
<210> 629
<211> 102
<212> PRT
<213> 人工序列
<220>
<223> GLEW类纳米体
<220>
<221> misc_feature
<222> (31)..(35)
<223> CDR
<220>
<221> misc_feature
<222> (31)..(35)
<223> Xaa为任何氨基酸
<220>
<221> misc_feature
<222> (50)..(54)
<223> CDR
<220>
<221> misc_feature
<222> (50)..(54)
<223> Xaa为任何氨基酸
<220>
<221> misc_feature
<222> (87)..(91)
<223> CDR
<220>
<221> misc_feature
<222> (87)..(91)
<223> Xaa为任何氨基酸
<400> 629
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Ala Leu Pro Gly Gly
1 5 10 15
Ser Leu Thr Leu Ser Cys Val Phe Ser Gly Ser Thr Phe Ser Xaa Xaa
20 25 30
Xaa Xaa Xaa Trp Val Arg His Thr Pro Gly Lys Ala Glu Glu Trp Val
35 40 45
Ser Xaa Xaa Xaa Xaa Xaa Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys
50 55 60
Asn Thr Leu Tyr Leu Glu Met Asn Ser Leu Ser Pro Glu Asp Thr Ala
65 70 75 80
Met Tyr Tyr Cys Gly Arg Xaa Xaa Xaa Xaa Xaa Arg Ser Lys Gly Ile
85 90 95
Gln Val Thr Val Ser Ser
100
<210> 630
<211> 102
<212> PRT
<213> 人工序列
<220>
<223> P,R,S 103类纳米体
<220>
<221> misc_feature
<222> (31)..(35)
<223> CDR
<220>
<221> misc_feature
<222> (31)..(35)
<223> Xaa为任何氨基酸
<220>
<221> misc_feature
<222> (50)..(54)
<223> CDR
<220>
<221> misc_feature
<222> (50)..(54)
<223> Xaa为任何氨基酸
<220>
<221> misc_feature
<222> (87)..(91)
<223> CDR
<220>
<221> misc_feature
<222> (87)..(91)
<223> Xaa为任何氨基酸
<400> 630
Ala Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Arg Thr Phe Ser Xaa Xaa
20 25 30
Xaa Xaa Xaa Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ala Xaa Xaa Xaa Xaa Xaa Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys
50 55 60
Asn Thr Val Tyr Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala
65 70 75 80
Val Tyr Tyr Cys Ala Ala Xaa Xaa Xaa Xaa Xaa Arg Gly Gln Gly Thr
85 90 95
Gln Val Thr Val Ser Ser
100
<210> 631
<211> 102
<212> PRT
<213> 人工序列
<220>
<223> P,R,S 103类纳米体
<220>
<221> misc_feature
<222> (31)..(35)
<223> CDR
<220>
<221> misc_feature
<222> (31)..(35)
<223> Xaa为任何氨基酸
<220>
<221> misc_feature
<222> (50)..(54)
<223> CDR
<220>
<221> misc_feature
<222> (50)..(54)
<223> Xaa为任何氨基酸
<220>
<221> misc_feature
<222> (87)..(91)
<223> CDR
<220>
<221> misc_feature
<222> (87)..(91)
<223> Xaa为任何氨基酸
<400> 631
Asp Val Gln Leu Val Glu Ser Gly Gly Asp Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Phe Asp Xaa Xaa
20 25 30
Xaa Xaa Xaa Trp Leu Arg Gln Thr Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Gly Xaa Xaa Xaa Xaa Xaa Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys
50 55 60
Asn Met Leu Tyr Leu His Leu Asn Asn Leu Lys Ser Glu Asp Thr Ala
65 70 75 80
Val Tyr Tyr Cys Arg Arg Xaa Xaa Xaa Xaa Xaa Leu Gly Gln Gly Thr
85 90 95
Gln Val Thr Val Ser Ser
100
<210> 632
<211> 102
<212> PRT
<213> 人工序列
<220>
<223> P,R,S 103类纳米体
<220>
<221> misc_feature
<222> (31)..(35)
<223> CDR
<220>
<221> misc_feature
<222> (31)..(35)
<223> Xaa为任何氨基酸
<220>
<221> misc_feature
<222> (50)..(54)
<223> CDR
<220>
<221> misc_feature
<222> (50)..(54)
<223> Xaa为任何氨基酸
<220>
<221> misc_feature
<222> (87)..(91)
<223> CDR
<220>
<221> misc_feature
<222> (87)..(91)
<223> Xaa为任何氨基酸
<400> 632
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 Val Cys Val Ser Ser Gly Cys Thr Xaa Xaa
20 25 30
Xaa Xaa Xaa Trp Val Arg Gln Ala Pro Gly Lys Ala Glu Glu Trp Val
35 40 45
Ser Xaa Xaa Xaa Xaa Xaa Arg Phe Lys Ile Ser Arg Asp Asn Ala Lys
50 55 60
Lys Thr Leu Tyr Leu Gln Met Asn Ser Leu Gly Pro Glu Asp Thr Ala
65 70 75 80
Met Tyr Tyr Cys Gln Arg Xaa Xaa Xaa Xaa Xaa Arg Gly Gln Gly Thr
85 90 95
Gln Val Thr Val Ser Ser
100
<210> 633
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体FW1序列
<400> 633
Gln Val Gln Arg Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Ser
20 25 30
<210> 634
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体FW1序列
<400> 634
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Thr Gly Asp
1 5 10 15
Ser Leu Ser Leu Ser Cys Ser Ala Ser Gly Arg Thr Phe Ser
20 25 30
<210> 635
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体FW1序列
<400> 635
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Asp
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Thr Gly Arg Ala Phe Gly
20 25 30
<210> 636
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体FW1序列
<400> 636
Ala Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Glu
1 5 10 15
Ser Leu Gly Leu Ser Cys Val Ala Ser Gly Arg Asp Phe Val
20 25 30
<210> 637
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体FW1序列
<400> 637
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Glu Val Leu Gly Arg Thr Ala Gly
20 25 30
<210> 638
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体FW1序列
<400> 638
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Trp Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Glu Thr Ile Leu Ser
20 25 30
<210> 639
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体FW1序列
<400> 639
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Thr Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Asn Leu Ser Cys Val Ala Ser Gly Asn Thr Phe Asn
20 25 30
<210> 640
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体FW1序列
<400> 640
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Ala Gln Pro Gly Gly
1 5 10 15
Ser Leu Gln Leu Ser Cys Ser Ala Pro Gly Phe Thr Leu Asp
20 25 30
<210> 641
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体FW1序列
<400> 641
Ala Gln Glu Leu Glu Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Arg Thr Phe Asn
20 25 30
<210> 642
<211> 22
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体FW1序列
<400> 642
Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu
1 5 10 15
Ser Cys Ala Ala Ser Gly
20
<210> 643
<211> 22
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体FW1序列
<400> 643
Val Asp Ser Gly Gly Gly Leu Val Gln Ala Gly Asp Ser Leu Lys Leu
1 5 10 15
Ser Cys Ala Leu Thr Gly
20
<210> 644
<211> 22
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体FW1序列
<400> 644
Val Asp Ser Gly Gly Gly Leu Val Gln Ala Gly Asp Ser Leu Arg Leu
1 5 10 15
Ser Cys Ala Ala Ser Gly
20
<210> 645
<211> 22
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体FW1序列
<400> 645
Val Asp Ser Gly Gly Gly Leu Val Glu Ala Gly Gly Ser Leu Arg Leu
1 5 10 15
Ser Cys Gln Val Ser Glu
20
<210> 646
<211> 22
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体FW1序列
<400> 646
Gln Asp Ser Gly Gly Gly Ser Val Gln Ala Gly Gly Ser Leu Lys Leu
1 5 10 15
Ser Cys Ala Ala Ser Gly
20
<210> 647
<211> 22
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体FW1序列
<400> 647
Val Gln Ser Gly Gly Arg Leu Val Gln Ala Gly Asp Ser Leu Arg Leu
1 5 10 15
Ser Cys Ala Ala Ser Glu
20
<210> 648
<211> 22
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体FW1序列
<400> 648
Val Glu Ser Gly Gly Thr Leu Val Gln Ser Gly Asp Ser Leu Lys Leu
1 5 10 15
Ser Cys Ala Ser Ser Thr
20
<210> 649
<211> 22
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体FW1序列
<400> 649
Met Glu Ser Gly Gly Asp Ser Val Gln Ser Gly Gly Ser Leu Thr Leu
1 5 10 15
Ser Cys Val Ala Ser Gly
20
<210> 650
<211> 22
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体FW1序列
<400> 650
Gln Ala Ser Gly Gly Gly Leu Val Gln Ala Gly Gly Ser Leu Arg Leu
1 5 10 15
Ser Cys Ser Ala Ser Val
20
<210> 651
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体FW2序列
<400> 651
Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ala
1 5 10
<210> 652
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体FW2序列
<400> 652
Trp Phe Arg Gln Thr Pro Gly Arg Glu Arg Glu Phe Val Ala
1 5 10
<210> 653
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体FW2序列
<400> 653
Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Met Val Ala
1 5 10
<210> 654
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体FW2序列
<400> 654
Trp Tyr Arg Gln Gly Pro Gly Lys Gln Arg Glu Leu Val Ala
1 5 10
<210> 655
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体FW2序列
<400> 655
Trp Ile Arg Gln Ala Pro Gly Lys Glu Arg Glu Gly Val Ser
1 5 10
<210> 656
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体FW2序列
<400> 656
Trp Phe Arg Glu Ala Pro Gly Lys Glu Arg Glu Gly Ile Ser
1 5 10
<210> 657
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体FW2序列
<400> 657
Trp Tyr Arg Gln Ala Pro Gly Lys Glu Arg Asp Leu Val Ala
1 5 10
<210> 658
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体FW2序列
<400> 658
Trp Phe Arg Gln Ala Pro Gly Lys Gln Arg Glu Glu Val Ser
1 5 10
<210> 659
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体FW2序列
<400> 659
Trp Phe Arg Gln Pro Pro Gly Lys Val Arg Glu Phe Val Gly
1 5 10
<210> 660
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体FW3序列
<400> 660
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Tyr Leu Gln
1 5 10 15
Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr Arg Cys Tyr Phe
20 25 30
<210> 661
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体FW3序列
<400> 661
Arg Phe Ala Ile Ser Arg Asp Asn Asn Lys Asn Thr Gly Tyr Leu Gln
1 5 10 15
Met Asn Ser Leu Glu Pro Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala
20 25 30
<210> 662
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体FW3序列
<400> 662
Arg Phe Thr Val Ala Arg Asn Asn Ala Lys Asn Thr Val Asn Leu Glu
1 5 10 15
Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala
20 25 30
<210> 663
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体FW3序列
<400> 663
Arg Phe Thr Ile Ser Arg Asp Ile Ala Lys Asn Thr Val Asp Leu Leu
1 5 10 15
Met Asn Asn Leu Glu Pro Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala
20 25 30
<210> 664
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体FW3序列
<400> 664
Arg Leu Thr Ile Ser Arg Asp Asn Ala Val Asp Thr Met Tyr Leu Gln
1 5 10 15
Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala
20 25 30
<210> 665
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体FW3序列
<400> 665
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Tyr Leu Gln
1 5 10 15
Met Asp Asn Val Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala
20 25 30
<210> 666
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体FW3序列
<400> 666
Arg Phe Thr Ile Ser Lys Asp Ser Gly Lys Asn Thr Val Tyr Leu Gln
1 5 10 15
Met Thr Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr
20 25 30
<210> 667
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体FW3序列
<400> 667
Arg Phe Thr Ile Ser Arg Asp Ser Ala Lys Asn Met Met Tyr Leu Gln
1 5 10 15
Met Asn Asn Leu Lys Pro Gln Asp Thr Ala Val Tyr Tyr Cys Ala Ala
20 25 30
<210> 668
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体FW3序列
<400> 668
Arg Phe Thr Ile Ser Arg Glu Asn Asp Lys Ser Thr Val Tyr Leu Gln
1 5 10 15
Leu Asn Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala
20 25 30
<210> 669
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体FW3序列
<400> 669
Arg Phe Thr Ile Ser Arg Asp Tyr Ala Gly Asn Thr Ala Tyr Leu Gln
1 5 10 15
Met Asn Ser Leu Lys Pro Glu Asp Thr Gly Val Tyr Tyr Cys Ala Thr
20 25 30
<210> 670
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体FW4序列
<400> 670
Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser
1 5 10
<210> 671
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体FW4序列
<400> 671
Trp Gly Lys Gly Thr Leu Val Thr Val Ser Ser
1 5 10
<210> 672
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体FW4序列
<400> 672
Arg Gly Gln Gly Thr Arg Val Thr Val Ser Ser
1 5 10
<210> 673
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> KERE类纳米体FW4序列
<400> 673
Trp Gly Leu Gly Thr Gln Val Thr Ile Ser Ser
1 5 10
<210> 674
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> GLEW类纳米体FW1序列
<400> 674
Gln 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 Thr Phe Ser
20 25 30
<210> 675
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> GLEW类纳米体FW1序列
<400> 675
Glu Val His Leu Val Glu Ser Gly Gly Gly Leu Val Arg Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Phe Gly Phe Ile Phe Lys
20 25 30
<210> 676
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> GLEW类纳米体FW1序列
<400> 676
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Leu Ala Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Val Ala Ser Gly Phe Thr Phe Ser
20 25 30
<210> 677
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> GLEW类纳米体FW1序列
<400> 677
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 Val Cys Val Ser Ser Gly Cys Thr
20 25 30
<210> 678
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> GLEW类纳米体FW1序列
<400> 678
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Ala Leu Pro Gly Gly
1 5 10 15
Ser Leu Thr Leu Ser Cys Val Phe Ser Gly Ser Thr Phe Ser
20 25 30
<210> 679
<211> 22
<212> PRT
<213> 人工序列
<220>
<223> GLEW类纳米体FW1序列
<400> 679
Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu
1 5 10 15
Ser Cys Ala Ala Ser Gly
20
<210> 680
<211> 22
<212> PRT
<213> 人工序列
<220>
<223> GLEW类纳米体FW1序列
<400> 680
Glu Glu Ser Gly Gly Gly Leu Ala Gln Pro Gly Gly Ser Leu Arg Leu
1 5 10 15
Ser Cys Val Ala Ser Gly
20
<210> 681
<211> 22
<212> PRT
<213> 人工序列
<220>
<223> GLEW类纳米体FW1序列
<400> 681
Val Glu Ser Gly Gly Gly Leu Ala Leu Pro Gly Gly Ser Leu Thr Leu
1 5 10 15
Ser Cys Val Phe Ser Gly
20
<210> 682
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> GLEW类纳米体FW2序列
<400> 682
Trp Val Arg Gln Ala Pro Gly Lys Val Leu Glu Trp Val Ser
1 5 10
<210> 683
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> GLEW类纳米体FW2序列
<400> 683
Trp Val Arg Arg Pro Pro Gly Lys Gly Leu Glu Trp Val Ser
1 5 10
<210> 684
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> GLEW类纳米体FW2序列
<400> 684
Trp Val Arg Gln Ala Pro Gly Met Gly Leu Glu Trp Val Ser
1 5 10
<210> 685
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> GLEW类纳米体FW2序列
<400> 685
Trp Val Arg Gln Ala Pro Gly Lys Glu Pro Glu Trp Val Ser
1 5 10
<210> 686
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> GLEW类纳米体FW2序列
<400> 686
Trp Val Arg Gln Ala Pro Gly Lys Asp Gln Glu Trp Val Ser
1 5 10
<210> 687
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> GLEW类纳米体FW2序列
<400> 687
Trp Val Arg Gln Ala Pro Gly Lys Ala Glu Glu Trp Val Ser
1 5 10
<210> 688
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> GLEW类纳米体FW2序列
<400> 688
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala
1 5 10
<210> 689
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> GLEW类纳米体FW2序列
<400> 689
Trp Val Arg Gln Ala Pro Gly Arg Ala Thr Glu Trp Val Ser
1 5 10
<210> 690
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> GLEW类纳米体FW3序列
<400> 690
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr Leu Gln
1 5 10 15
Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr Tyr Cys Val Lys
20 25 30
<210> 691
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> GLEW类纳米体FW3序列
<400> 691
Arg Phe Thr Ile Ser Arg Asp Asn Ala Arg Asn Thr Leu Tyr Leu Gln
1 5 10 15
Met Asp Ser Leu Ile Pro Glu Asp Thr Ala Leu Tyr Tyr Cys Ala Arg
20 25 30
<210> 692
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> GLEW类纳米体FW3序列
<400> 692
Arg Phe Thr Ser Ser Arg Asp Asn Ala Lys Ser Thr Leu Tyr Leu Gln
1 5 10 15
Met Asn Asp Leu Lys Pro Glu Asp Thr Ala Leu Tyr Tyr Cys Ala Arg
20 25 30
<210> 693
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> GLEW类纳米体FW3序列
<400> 693
Arg Phe Ile Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr Leu Gln
1 5 10 15
Met Asn Ser Leu Gly Pro Glu Asp Thr Ala Met Tyr Tyr Cys Gln Arg
20 25 30
<210> 694
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> GLEW类纳米体FW3序列
<400> 694
Arg Phe Thr Ala Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr Leu Gln
1 5 10 15
Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Arg Tyr Tyr Cys Ala Arg
20 25 30
<210> 695
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> GLEW类纳米体FW3序列
<400> 695
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr Leu Gln
1 5 10 15
Met Asp Asp Leu Gln Ser Glu Asp Thr Ala Met Tyr Tyr Cys Gly Arg
20 25 30
<210> 696
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> GLEW类纳米体FW4序列
<400> 696
Gly Ser Gln Gly Thr Gln Val Thr Val Ser Ser
1 5 10
<210> 697
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> GLEW类纳米体FW4序列
<400> 697
Leu Arg Gly Gly Thr Gln Val Thr Val Ser Ser
1 5 10
<210> 698
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> GLEW类纳米体FW4序列
<400> 698
Arg Gly Gln Gly Thr Leu Val Thr Val Ser Ser
1 5 10
<210> 699
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> GLEW类纳米体FW4序列
<400> 699
Arg Ser Arg Gly Ile Gln Val Thr Val Ser Ser
1 5 10
<210> 700
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> GLEW类纳米体FW4序列
<400> 700
Trp Gly Lys Gly Thr Gln Val Thr Val Ser Ser
1 5 10
<210> 701
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> GLEW类纳米体FW4序列
<400> 701
Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser
1 5 10
<210> 702
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> P,R,S 103类纳米体FW1序列
<400> 702
Ala Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Arg Thr Phe Ser
20 25 30
<210> 703
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> P,R,S 103类纳米体FW1序列
<400> 703
Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Met Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asp Phe Gly
20 25 30
<210> 704
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> P,R,S 103类纳米体FW1序列
<400> 704
Glu Val His Leu Val Glu Ser Gly Gly Gly Leu Val Arg Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Phe Gly Phe Ile Phe Lys
20 25 30
<210> 705
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> P,R,S 103类纳米体FW1序列
<400> 705
Gln Val Gln Leu Ala Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Lys Leu Ser Cys Ala Ala Ser Arg Thr Ile Val Ser
20 25 30
<210> 706
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> P,R,S 103类纳米体FW1序列
<400> 706
Gln Glu His Leu Val Glu Ser Gly Gly Gly Leu Val Asp Ile Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Glu Arg Ile Phe Ser
20 25 30
<210> 707
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> P,R,S 103类纳米体FW1序列
<400> 707
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Leu Ala Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Val Ala Ser Gly Phe Thr Phe Ser
20 25 30
<210> 708
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> P,R,S 103类纳米体FW1序列
<400> 708
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 Val Cys Val Ser Ser Gly Cys Thr
20 25 30
<210> 709
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> P,R,S 103类纳米体FW1序列
<400> 709
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Ala Leu Pro Gly Gly
1 5 10 15
Ser Leu Thr Leu Ser Cys Val Phe Ser Gly Ser Thr Phe Ser
20 25 30
<210> 710
<211> 22
<212> PRT
<213> 人工序列
<220>
<223> P,R,S 103类纳米体FW1序列
<400> 710
Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly Ser Leu Arg Leu
1 5 10 15
Ser Cys Ala Ala Ser Gly
20
<210> 711
<211> 22
<212> PRT
<213> 人工序列
<220>
<223> P,R,S 103类纳米体FW1序列
<400> 711
Ala Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu
1 5 10 15
Ser Cys Ala Ala Ser Arg
20
<210> 712
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> P,R,S 103类纳米体FW2序列
<400> 712
Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ala
1 5 10
<210> 713
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> P,R,S 103类纳米体FW2序列
<400> 713
Trp Val Arg Gln Ala Pro Gly Lys Val Leu Glu Trp Val Ser
1 5 10
<210> 714
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> P,R,S 103类纳米体FW2序列
<400> 714
Trp Val Arg Arg Pro Pro Gly Lys Gly Leu Glu Trp Val Ser
1 5 10
<210> 715
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> P,R,S 103类纳米体FW2序列
<400> 715
Trp Ile Arg Gln Ala Pro Gly Lys Glu Arg Glu Gly Val Ser
1 5 10
<210> 716
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> P,R,S 103类纳米体FW2序列
<400> 716
Trp Val Arg Gln Tyr Pro Gly Lys Glu Pro Glu Trp Val Ser
1 5 10
<210> 717
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> P,R,S 103类纳米体FW2序列
<400> 717
Trp Phe Arg Gln Pro Pro Gly Lys Glu His Glu Phe Val Ala
1 5 10
<210> 718
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> P,R,S 103类纳米体FW2序列
<400> 718
Trp Tyr Arg Gln Ala Pro Gly Lys Arg Thr Glu Leu Val Ala
1 5 10
<210> 719
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> P,R,S 103类纳米体FW2序列
<400> 719
Trp Leu Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Val Ser
1 5 10
<210> 720
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> P,R,S 103类纳米体FW2序列
<400> 720
Trp Leu Arg Gln Thr Pro Gly Lys Gly Leu Glu Trp Val Gly
1 5 10
<210> 721
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> P,R,S 103类纳米体FW2序列
<400> 721
Trp Val Arg Gln Ala Pro Gly Lys Ala Glu Glu Phe Val Ser
1 5 10
<210> 722
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> P,R,S 103类纳米体FW3序列
<400> 722
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Tyr Leu Gln
1 5 10 15
Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala
20 25 30
<210> 723
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> P,R,S 103类纳米体FW3序列
<400> 723
Arg Phe Thr Ile Ser Arg Asp Asn Ala Arg Asn Thr Leu Tyr Leu Gln
1 5 10 15
Met Asp Ser Leu Ile Pro Glu Asp Thr Ala Leu Tyr Tyr Cys Ala Arg
20 25 30
<210> 724
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> P,R,S 103类纳米体FW3序列
<400> 724
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Glu Met Tyr Leu Gln
1 5 10 15
Met Asn Asn Leu Lys Thr Glu Asp Thr Gly Val Tyr Trp Cys Gly Ala
20 25 30
<210> 725
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> P,R,S 103类纳米体FW3序列
<400> 725
Arg Phe Thr Ile Ser Ser Asp Ser Asn Arg Asn Met Ile Tyr Leu Gln
1 5 10 15
Met Asn Asn Leu Lys Pro Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala
20 25 30
<210> 726
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> P,R,S 103类纳米体FW3序列
<400> 726
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Met Leu Tyr Leu His
1 5 10 15
Leu Asn Asn Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys Arg Arg
20 25 30
<210> 727
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> P,R,S 103类纳米体FW3序列
<400> 727
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Lys Thr Val Tyr Leu Arg
1 5 10 15
Leu Asn Ser Leu Asn Pro Glu Asp Thr Ala Val Tyr Ser Cys Asn Leu
20 25 30
<210> 728
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> P,R,S 103类纳米体FW3序列
<400> 728
Arg Phe Lys Ile Ser Arg Asp Asn Ala Lys Lys Thr Leu Tyr Leu Gln
1 5 10 15
Met Asn Ser Leu Gly Pro Glu Asp Thr Ala Met Tyr Tyr Cys Gln Arg
20 25 30
<210> 729
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> P,R,S 103类纳米体FW3序列
<400> 729
Arg Phe Thr Val Ser Arg Asp Asn Gly Lys Asn Thr Ala Tyr Leu Arg
1 5 10 15
Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Asp Tyr Tyr Cys Ala Val
20 25 30
<210> 730
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> P,R,S 103类纳米体FW4序列
<400> 730
Arg Gly Gln Gly Thr Gln Val Thr Val Ser Ser
1 5 10
<210> 731
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> P,R,S 103类纳米体FW4序列
<400> 731
Leu Arg Gly Gly Thr Gln Val Thr Val Ser Ser
1 5 10
<210> 732
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> P,R,S 103类纳米体FW4序列
<400> 732
Gly Asn Lys Gly Thr Leu Val Thr Val Ser Ser
1 5 10
<210> 733
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> P,R,S 103类纳米体FW4序列
<400> 733
Ser Ser Pro Gly Thr Gln Val Thr Val Ser Ser
1 5 10
<210> 734
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> P,R,S 103类纳米体FW4序列
<400> 734
Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser
1 5 10
<210> 735
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> P,R,S 103类纳米体FW4序列
<400> 735
Arg Ser Arg Gly Ile Gln Val Thr Val Ser Ser
1 5 10
<210> 736
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> FR1序列
<400> 736
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 Ser Ile Phe Ser
20 25 30
<210> 737
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> FR1序列
<400> 737
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Asp
1 5 10 15
Ser Leu Arg Leu Ser Cys Thr Ala Thr Gly Arg Thr Ser Ser
20 25 30
<210> 738
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> FR1序列
<400> 738
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Thr Ser Gly Phe Thr Phe Ser
20 25 30
<210> 739
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> FR1序列
<400> 739
Lys Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Arg Thr Phe Ser
20 25 30
<210> 740
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> FR1序列
<400> 740
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Asp
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Thr Gly Arg Thr Ser Ser
20 25 30
<210> 741
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> FR1序列
<400> 741
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Val Ala Ser Gly Arg Thr Leu Arg
20 25 30
<210> 742
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> FR1序列
<400> 742
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Phe Ser
20 25 30
<210> 743
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> FR1序列
<400> 743
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Leu Thr Phe Asn
20 25 30
<210> 744
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> FR1序列
<400> 744
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Asp
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Thr Gly Arg Thr Ser Ser
20 25 30
<210> 745
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> CDR序列
<400> 745
Asp Asn Val Met Gly
1 5
<210> 746
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> CDR序列
<400> 746
Ile Tyr Asn Met Asp
1 5
<210> 747
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> CDR序列
<400> 747
Arg Phe Asp Met Ser
1 5
<210> 748
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> CDR序列
<400> 748
Ser Tyr Phe Met Gly
1 5
<210> 749
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> CDR序列
<400> 749
Ile Tyr Asn Met Asp
1 5
<210> 750
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> CDR序列
<400> 750
Arg Tyr Val Thr Gly
1 5
<210> 751
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> CDR序列
<400> 751
Ser Phe Val Ile Gly
1 5
<210> 752
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> CDR序列
<400> 752
Gln Tyr Thr Ile Thr
1 5
<210> 753
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> CDR序列
<400> 753
Ile Tyr Asn Met Asp
1 5
<210> 754
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> FR2序列
<400> 754
Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val Ala
1 5 10
<210> 755
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> FR2序列
<400> 755
Trp Phe Arg Gln Thr Pro Gly Lys Glu Arg Glu Leu Ile Ala
1 5 10
<210> 756
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> FR2序列
<400> 756
Trp Phe Arg Gln Ala Pro Gly Lys Gln Arg Glu Phe Ile Ala
1 5 10
<210> 757
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> FR2序列
<400> 757
Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Val Val Ala
1 5 10
<210> 758
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> FR2序列
<400> 758
Trp Phe Leu Gln Ala Pro Gly Lys Glu Arg Glu Leu Ile Ala
1 5 10
<210> 759
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> FR2序列
<400> 759
Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Val Val Ala
1 5 10
<210> 760
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> FR2序列
<400> 760
Trp Phe Arg Gln Ala Pro Gly Lys Gln Arg Glu Val Val Ala
1 5 10
<210> 761
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> FR2序列
<400> 761
Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ala
1 5 10
<210> 762
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> FR2序列
<400> 762
Trp Phe Arg Gln Gly Ser Gly Lys Gly Arg Glu Leu Ile Ala
1 5 10
<210> 763
<211> 16
<212> PRT
<213> 人工序列
<220>
<223> CDR序列
<400> 763
Thr Ile Trp Ser Ser Gly His Thr Asn Tyr Ala Asp Ser Val Lys Gly
1 5 10 15
<210> 764
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> CDR序列
<400> 764
Arg Leu Trp Trp Arg Ser Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys
1 5 10 15
Gly
<210> 765
<211> 16
<212> PRT
<213> 人工序列
<220>
<223> CDR序列
<400> 765
Thr Ile Phe Ser Gly Gly Asp Thr Asp Tyr Ile Asp Ser Val Lys Gly
1 5 10 15
<210> 766
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> CDR序列
<400> 766
Thr Ile Arg Trp Ser Asp Gly Ser Thr Tyr Tyr Glu Asp Ser Val Lys
1 5 10 15
Gly
<210> 767
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> CDR序列
<400> 767
Arg Ile Trp Trp Arg Ser Gly Ala Thr Tyr Tyr Ala Asp Ser Val Lys
1 5 10 15
Gly
<210> 768
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> CDR序列
<400> 768
Ser Ile Ser Trp Ser Gly Glu Ser Thr Tyr Tyr Ala Asp Ser Val Lys
1 5 10 15
Gly
<210> 769
<211> 16
<212> PRT
<213> 人工序列
<220>
<223> CDR序列
<400> 769
Ser Ile Thr Ser Gly Gly Ser Thr Tyr Tyr Glu Asp Ser Gly Lys Gly
1 5 10 15
<210> 770
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> CDR序列
<400> 770
Ala Val Ser Trp Ser Gly Ser Ser Glu Ser Val Ser Asn Ser Val Lys
1 5 10 15
Gly
<210> 771
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> CDR序列
<400> 771
Arg Ile Trp Trp Arg Ser Gly Glu Thr Tyr Tyr Ala Asp Ser Val Lys
1 5 10 15
Gly
<210> 772
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> FR3序列
<400> 772
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Tyr Leu Gln
1 5 10 15
Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr Tyr Cys Asn Leu
20 25 30
<210> 773
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> FR3序列
<400> 773
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Tyr Leu Gln
1 5 10 15
Met Asn Ser Leu Lys Pro Glu Asp Thr Ser Val Tyr Ile Cys Thr Ala
20 25 30
<210> 774
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> FR3序列
<400> 774
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Tyr Leu Gln
1 5 10 15
Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr Tyr Cys Cys Pro
20 25 30
<210> 775
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> FR3序列
<400> 775
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Tyr Leu Gln
1 5 10 15
Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala
20 25 30
<210> 776
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> FR3序列
<400> 776
Arg Phe Thr Ile Ser Arg Gly Asn Ala Lys Asn Thr Val Tyr Leu Gln
1 5 10 15
Met Asn Ser Leu Lys Pro Glu Asp Thr Gly Val Tyr His Cys Thr Ala
20 25 30
<210> 777
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> FR3序列
<400> 777
Arg Phe Ala Ile Ser Arg Asp Asn Ala Lys Asn Ala Val Tyr Leu Gln
1 5 10 15
Met Asn Ser Leu Asn Leu Glu Asp Thr Gly Val Tyr Tyr Cys Ala Glu
20 25 30
<210> 778
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> FR3序列
<400> 778
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Arg Val Tyr Leu Gln
1 5 10 15
Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala
20 25 30
<210> 779
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> FR3序列
<400> 779
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Ala Tyr Leu Ala
1 5 10 15
Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala
20 25 30
<210> 780
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> FR3序列
<400> 780
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Tyr Leu Gln
1 5 10 15
Met Asn Ser Leu Lys Pro Glu Asp Thr Asn Val Tyr His Cys Ala Ala
20 25 30
<210> 781
<211> 12
<212> PRT
<213> 人工序列
<220>
<223> CDR序列
<400> 781
Gly Thr Ile Val Thr Gly Thr Trp Arg Ser Asp Tyr
1 5 10
<210> 782
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> CDR序列
<400> 782
Gly Asp Thr Gly Gly Ala Ala Tyr Gly Tyr
1 5 10
<210> 783
<211> 6
<212> PRT
<213> 人工序列
<220>
<223> CDR序列
<400> 783
Leu Gly Ile Glu Tyr Ala
1 5
<210> 784
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> CDR序列
<400> 784
Ala Lys Gly Ile Gly Val Tyr Gly Tyr
1 5
<210> 785
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> CDR序列
<400> 785
Gly Val Thr Gly Gly Ala Ala Tyr Gly Tyr
1 5 10
<210> 786
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> CDR序列
<400> 786
Ala Glu Leu Pro Gly Thr Tyr Asp Tyr
1 5
<210> 787
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> CDR序列
<400> 787
Ala Glu Pro Ala Gly Val Tyr Asp Val
1 5
<210> 788
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> CDR序列
<400> 788
Asp Arg Arg Gly Leu Ala Ser Thr Arg Ala Ala Asp Tyr Asp Tyr
1 5 10 15
<210> 789
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> CDR序列
<400> 789
Gly Asp Thr Gly Gly Ala Ser Tyr Gly Tyr
1 5 10
<210> 790
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> FR4序列
<400> 790
Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser
1 5 10
<210> 791
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> FR4序列
<400> 791
Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser
1 5 10
<210> 792
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> FR4序列
<400> 792
Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser
1 5 10
<210> 793
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> FR4序列
<400> 793
Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser
1 5 10
<210> 794
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> FR4序列
<400> 794
Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser
1 5 10
<210> 795
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> FR4序列
<400> 795
Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser
1 5 10
<210> 796
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> FR4序列
<400> 796
Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser
1 5 10
<210> 797
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> FR4序列
<400> 797
Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser
1 5 10
<210> 798
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> FR4序列
<400> 798
Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser
1 5 10
<210> 799
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 纳米体
<400> 799
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 Ser Ile Phe Ser Asp Asn
20 25 30
Val Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val
35 40 45
Ala Thr Ile Trp Ser Ser Gly His Thr Asn Tyr Ala Asp Ser Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr Tyr Cys Asn
85 90 95
Leu Gly Thr Ile Val Thr Gly Thr Trp Arg Ser Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Gln Val Thr Val Ser Ser
115 120
<210> 800
<211> 119
<212> PRT
<213> 人工序列
<220>
<223> 纳米体
<400> 800
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Asp
1 5 10 15
Ser Leu Arg Leu Ser Cys Thr Ala Thr Gly Arg Thr Ser Ser Ile Tyr
20 25 30
Asn Met Asp Trp Phe Arg Gln Thr Pro Gly Lys Glu Arg Glu Leu Ile
35 40 45
Ala Arg Leu Trp Trp Arg Ser Gly Ser Thr Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ser Val Tyr Ile Cys
85 90 95
Thr Ala Gly Asp Thr Gly Gly Ala Ala Tyr Gly Tyr Trp Gly Gln Gly
100 105 110
Thr Gln Val Thr Val Ser Ser
115
<210> 801
<211> 114
<212> PRT
<213> 人工序列
<220>
<223> 纳米体
<400> 801
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Thr Ser Gly Phe Thr Phe Ser Arg Phe
20 25 30
Asp Met Ser Trp Phe Arg Gln Ala Pro Gly Lys Gln Arg Glu Phe Ile
35 40 45
Ala Thr Ile Phe Ser Gly Gly Asp Thr Asp Tyr Ile Asp Ser Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr Tyr Cys Cys
85 90 95
Pro Leu Gly Ile Glu Tyr Ala Trp Gly Gln Gly Thr Gln Val Thr Val
100 105 110
Ser Ser
<210> 802
<211> 118
<212> PRT
<213> 人工序列
<220>
<223> 纳米体
<400> 802
Lys Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Arg Thr Phe Ser Ser Tyr
20 25 30
Phe Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Val Val
35 40 45
Ala Thr Ile Arg Trp Ser Asp Gly Ser Thr Tyr Tyr Glu Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Ala Lys Gly Ile Gly Val Tyr Gly Tyr Trp Gly Gln Gly Thr
100 105 110
Gln Val Thr Val Ser Ser
115
<210> 803
<211> 119
<212> PRT
<213> 人工序列
<220>
<223> 纳米体
<400> 803
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Asp
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Thr Gly Arg Thr Ser Ser Ile Tyr
20 25 30
Asn Met Asp Trp Phe Leu Gln Ala Pro Gly Lys Glu Arg Glu Leu Ile
35 40 45
Ala Arg Ile Trp Trp Arg Ser Gly Ala Thr Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Gly Asn Ala Lys Asn Thr Val Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Gly Val Tyr His Cys
85 90 95
Thr Ala Gly Val Thr Gly Gly Ala Ala Tyr Gly Tyr Trp Gly Gln Gly
100 105 110
Thr Gln Val Thr Val Ser Ser
115
<210> 804
<211> 118
<212> PRT
<213> 人工序列
<220>
<223> 纳米体
<400> 804
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Val Ala Ser Gly Arg Thr Leu Arg Arg Tyr
20 25 30
Val Thr Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Val Val
35 40 45
Ala Ser Ile Ser Trp Ser Gly Glu Ser Thr Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Ala Ile Ser Arg Asp Asn Ala Lys Asn Ala Val Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Asn Leu Glu Asp Thr Gly Val Tyr Tyr Cys
85 90 95
Ala Glu Ala Glu Leu Pro Gly Thr Tyr Asp Tyr Trp Gly Gln Gly Thr
100 105 110
Gln Val Thr Val Ser Ser
115
<210> 805
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 纳米体
<400> 805
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Phe Ser Ser Phe
20 25 30
Val Ile Gly Trp Phe Arg Gln Ala Pro Gly Lys Gln Arg Glu Val Val
35 40 45
Ala Ser Ile Thr Ser Gly Gly Ser Thr Tyr Tyr Glu Asp Ser Gly Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Arg Val Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Ala
85 90 95
Ala Ala Glu Pro Ala Gly Val Tyr Asp Val Trp Gly Gln Gly Thr Gln
100 105 110
Val Thr Val Ser Ser
115
<210> 806
<211> 124
<212> PRT
<213> 人工序列
<220>
<223> 纳米体
<400> 806
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Leu Thr Phe Asn Gln Tyr
20 25 30
Thr Ile Thr Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ala Ala Val Ser Trp Ser Gly Ser Ser Glu Ser Val Ser Asn Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Ala Tyr
65 70 75 80
Leu Ala Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Asp Arg Arg Gly Leu Ala Ser Thr Arg Ala Ala Asp Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser
115 120
<210> 807
<211> 119
<212> PRT
<213> 人工序列
<220>
<223> 纳米体
<400> 807
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Asp
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Thr Gly Arg Thr Ser Ser Ile Tyr
20 25 30
Asn Met Asp Trp Phe Arg Gln Gly Ser Gly Lys Gly Arg Glu Leu Ile
35 40 45
Ala Arg Ile Trp Trp Arg Ser Gly Glu Thr Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Asn Val Tyr His Cys
85 90 95
Ala Ala Gly Asp Thr Gly Gly Ala Ser Tyr Gly Tyr Trp Gly Gln Gly
100 105 110
Thr Gln Val Thr Val Ser Ser
115
<210> 808
<211> 213
<212> PRT
<213> 智人
<400> 808
Met Gln Leu Pro Leu Ala Leu Cys Leu Val Cys Leu Leu Val His Thr
1 5 10 15
Ala Phe Arg Val Val Glu Gly Gln Gly Trp Gln Ala Phe Lys Asn Asp
20 25 30
Ala Thr Glu Ile Ile Pro Glu Leu Gly Glu Tyr Pro Glu Pro Pro Pro
35 40 45
Glu Leu Glu Asn Asn Lys Thr Met Asn Arg Ala Glu Asn Gly Gly Arg
50 55 60
Pro Pro His His Pro Phe Glu Thr Lys Asp Val Ser Glu Tyr Ser Cys
65 70 75 80
Arg Glu Leu His Phe Thr Arg Tyr Val Thr Asp Gly Pro Cys Arg Ser
85 90 95
Ala Lys Pro Val Thr Glu Leu Val Cys Ser Gly Gln Cys Gly Pro Ala
100 105 110
Arg Leu Leu Pro Asn Ala Ile Gly Arg Gly Lys Trp Trp Arg Pro Ser
115 120 125
Gly Pro Asp Phe Arg Cys Ile Pro Asp Arg Tyr Arg Ala Gln Thr Val
130 135 140
Gln Leu Leu Cys Pro Gly Gly Glu Ala Pro Arg Ala Arg Lys Val Arg
145 150 155 160
Leu Val Ala Ser Cys Lys Cys Lys Arg Leu Thr Arg Phe His Asn Gln
165 170 175
Ser Glu Leu Lys Asp Phe Gly Thr Glu Ala Ala Arg Pro Gln Lys Gly
180 185 190
Arg Lys Pro Arg Pro Arg Ala Arg Ser Ala Lys Ala Asn Gln Ala Glu
195 200 205
Leu Glu Asn Ala Tyr
210
<210> 809
<211> 213
<212> PRT
<213> 人工序列
<220>
<223> 重组骨硬化蛋白
<400> 809
Met Pro Leu Leu Leu Leu Leu Pro Leu Leu Trp Ala Gly Ala Leu Ala
1 5 10 15
His His His His His His His Gln Gly Trp Gln Ala Phe Lys Asn Asp
20 25 30
Ala Thr Glu Ile Ile Pro Glu Leu Gly Glu Tyr Pro Glu Pro Pro Pro
35 40 45
Glu Leu Glu Asn Asn Lys Thr Met Asn Arg Ala Glu Asn Gly Gly Arg
50 55 60
Pro Pro His His Pro Phe Glu Thr Lys Asp Val Ser Glu Tyr Ser Cys
65 70 75 80
Arg Glu Leu His Phe Thr Arg Tyr Val Thr Asp Gly Pro Cys Arg Ser
85 90 95
Ala Lys Pro Val Thr Glu Leu Val Cys Ser Gly Gln Cys Gly Pro Ala
100 105 110
Arg Leu Leu Pro Asn Ala Ile Gly Arg Gly Lys Trp Trp Arg Pro Ser
115 120 125
Gly Pro Asp Phe Arg Cys Ile Pro Asp Arg Tyr Arg Ala Gln Arg Val
130 135 140
Gln Leu Leu Cys Pro Gly Gly Glu Ala Pro Arg Ala Arg Lys Val Arg
145 150 155 160
Leu Val Ala Ser Cys Lys Cys Lys Arg Leu Thr Arg Phe His Asn Gln
165 170 175
Ser Glu Leu Lys Asp Phe Gly Thr Glu Ala Ala Arg Pro Gln Lys Gly
180 185 190
Arg Lys Pro Arg Pro Arg Ala Arg Ser Ala Lys Ala Asn Gln Ala Glu
195 200 205
Leu Glu Asn Ala Tyr
210

Claims (32)

1.一种治疗受试者牙槽骨流失的方法,所述方法包括向所述受试者施用有效减小牙骨质-牙轴质接面与牙槽骨嵴之间的距离的量的抗骨硬化蛋白抗体,剂量为每周约5mg至约1,000mg。
2.如权利要求1所述的方法,其中截至治疗开始后六周,所述牙骨质-牙轴质接面与所述牙槽骨嵴之间的距离与治疗前距离相比减小了至少10%。
3.如权利要求1所述的方法,其中截至治疗开始后六周,牙槽骨高度与治疗前牙槽骨高度相比增加了至少10%。
4.如权利要求1所述的方法,其中截至治疗开始后六周,所述受试者的牙槽骨高度与治疗前牙槽骨高度相比增加了至少1mm。
5.如权利要求1所述的方法,其中截至治疗开始后六周,所述受试者的牙槽骨密度与治疗前牙槽骨密度相比增加了至少10%。
6.如权利要求1所述的方法,其中截至治疗开始后六周,牙槽骨体积分数与治疗前骨骼体积分数相比增加了至少10%。
7.如权利要求1所述的方法,其中所述抗体的施用量为约120-270mg。
8.如权利要求1所述的方法,其中所述抗骨硬化蛋白抗体每周施用两次。
9.如权利要求1所述的方法,其中所述抗骨硬化蛋白抗体局部地施用至所述受试者的患病牙龈区或患病牙周袋。
10.如权利要求1至9中任一项所述的方法,其中所述方法包括在施用所述抗骨硬化蛋白抗体之前,施用选自由或化学改性的四环素-3(CMT-3)组成的组的护理标准护理治疗剂。
11.如权利要求1至10中任一项所述的方法,其进一步包括施用选自由副甲状腺素、特立帕肽(teriparatide)、双膦酸盐、RANKL抗体以及DKK-1抗体组成的组的第二骨骼增强治疗剂。
12.如权利要求10所述的方法,其中所述第二骨骼增强治疗剂是在使用所述抗骨硬化蛋白抗体的治疗期结束之后施用。
13.如权利要求1所述的方法,其任选地包括施用足以维持牙槽骨的量的所述抗骨硬化蛋白抗体持续第二段时间。
14.如权利要1至13中任一项所述的方法,其中所述抗骨硬化蛋白抗体为包含重链和轻链的免疫球蛋白。
15.如权利要求1至13中任一项所述的方法,其中所述抗骨硬化蛋白抗体为对SEQ IDNO:1的骨硬化蛋白显示小于或等于1x10-9M的结合亲和力的抗体或其片段。
16.如权利要求1至15中任一项所述的方法,其中当与每孔的骨硬化蛋白摩尔数相比,每孔存在少于六倍过量的摩尔数的骨硬化蛋白结合位点时,在基于MC3T3细胞的矿化分析中,所述抗骨硬化蛋白抗体中和人骨硬化蛋白。
17.如权利要求1至13中任一项所述的方法,其中所述抗骨硬化蛋白抗体交叉封闭以下抗体中至少一者与骨硬化蛋白的结合:Ab-A、Ab-B、Ab-C、Ab-D、Ab-1、Ab-2、Ab-3、Ab-4、Ab-5、Ab-6、Ab-7、Ab-8、Ab-9、Ab-10、Ab-11、Ab-12、Ab-13、Ab-14、Ab-15、Ab-16、Ab-17、Ab-18、Ab-19、Ab-20、Ab-21、Ab-22、Ab-23以及Ab-24,和/或被以下抗体中至少一者交叉封闭与骨硬化蛋白的结合:Ab-A、Ab-B、Ab-C、Ab-D、Ab-1、Ab-2、Ab-3、Ab-4、Ab-5、Ab-6、Ab-7、Ab-8、Ab-9、Ab-10、Ab-11、Ab-12、Ab-13、Ab-14、Ab-15、Ab-16、Ab-17、Ab-18、Ab-19、Ab-20、Ab-21、Ab-22、Ab-23以及Ab-24。
18.如权利要求1至13中任一项所述的方法,其中所述抗骨硬化蛋白抗体包含SEQ IDNO:245的CDR-H1、SEQ ID NO:246的CDR-H2、SEQ ID NO:247的CDR-H3、SEQ ID NO:78的CDR-L1、SEQ ID NO:79的CDR-L2,以及SEQ ID NO:80的CDR-L3。
19.如权利要求18所述的方法,其中抗骨硬化蛋白抗体包含含有SEQ ID NO:378的重链以及含有SEQ ID NO 376的轻链。
20.一种包含抗骨硬化蛋白抗体的牙齿植入物,所述抗骨硬化蛋白抗体结合至包含SEQID NO:1中所阐明的氨基酸序列的骨硬化蛋肽多,其中所述抗骨硬化蛋白抗体对SEQ IDNO:1的骨硬化蛋白显示小于或等于1x10-9M的结合亲和力。
21.一种包含抗骨硬化蛋白抗体的凝胶或基质,所述抗骨硬化蛋白抗体结合至包含SEQID NO:1中所阐明的氨基酸序列的骨硬化蛋肽多,其中所述抗骨硬化蛋白抗体对SEQ IDNO:1的骨硬化蛋白显示小于或等于1x10-9M的结合亲和力。
22.一种抗骨硬化蛋白抗体,其用于在治疗受试者牙槽骨流失的方法中使用,所述方法包括施用有效减小牙骨质-牙轴质接面与牙槽骨嵴之间的距离的量的抗骨硬化蛋白抗体,剂量任选地为每周约5mg至约1,000mg。
23.根据权利要求22所述的抗骨硬化蛋白抗体,其中所述治疗牙槽骨流失的方法进一步包括施用选自由副甲状腺素、特立帕肽、双膦酸盐、RANKL抗体及DKK-1抗体组成的组的第二骨骼增强治疗剂。
24.根据权利要求23所述的抗骨硬化蛋白抗体,其中所述第二骨骼增强治疗剂是在使用所述抗骨硬化蛋白抗体的治疗期结束之后施用。
25.根据权利要求22所述的抗骨硬化蛋白抗体,其中所述治疗牙槽骨流失的方法任选地进一步包括施用足以维持牙槽骨的量的所述抗骨硬化蛋白抗体持续第二段时间。
26.如权利要求22至25中任一项所述的抗骨硬化蛋白抗体,其中所述抗骨硬化蛋白抗体为包含重链和轻链的免疫球蛋白。
27.如权利要求22至26中任一项所述的抗骨硬化蛋白抗体,其中所述抗骨硬化蛋白抗体为对SEQ ID NO:1的骨硬化蛋白显示小于或等于1x10-9M的结合亲和力的抗体或其片段。
28.如权利要求22至27中任一项所述的抗骨硬化蛋白抗体,其中当与每孔的骨硬化蛋白摩尔数相比,每孔存在少于六倍过量的摩尔数的骨硬化蛋白结合位点时,在基于MC3T3细胞的矿化分析中,所述抗骨硬化蛋白抗体中和人骨硬化蛋白。
29.如权利要求22至28中任一项所述的抗骨硬化蛋白抗体,其中所述抗骨硬化蛋白抗体交叉封闭以下抗体中至少一者与骨硬化蛋白的结合:Ab-A、Ab-B、Ab-C、Ab-D、Ab-1、Ab-2、Ab-3、Ab-4、Ab-5、Ab-6、Ab-7、Ab-8、Ab-9、Ab-10、Ab-11、Ab-12、Ab-13、Ab-14、Ab-15、Ab-16、Ab-17、Ab-18、Ab-19、Ab-20、Ab-21、Ab-22、Ab-23以及Ab-24,和/或被以下抗体中至少一者交叉封闭与骨硬化蛋白的结合:Ab-A、Ab-B、Ab-C、Ab-D、Ab-1、Ab-2、Ab-3、Ab-4、Ab-5、Ab-6、Ab-7、Ab-8、Ab-9、Ab-10、Ab-11、Ab-12、Ab-13、Ab-14、Ab-15、Ab-16、Ab-17、Ab-18、Ab-19、Ab-20、Ab-21、Ab-22、Ab-23以及Ab-24。
30.如权利要求22至29中任一项所述的抗骨硬化蛋白抗体,其中所述抗骨硬化蛋白抗体包含SEQ ID NO:245的CDR-H1、SEQ ID NO:246的CDR-H2、SEQ ID NO:247的CDR-H3、SEQID NO:78的CDR-L1、SEQ ID NO:79的CDR-L2,以及SEQ ID NO:80的CDR-L3。
31.如权利要求30所述的抗骨硬化蛋白抗体,其中抗骨硬化蛋白抗体包含含有SEQ IDNO:378的重链及含有SEQ ID NO 376的轻链。
32.一种抗骨硬化蛋白抗体的用途,其用于制备供治疗受试者牙槽骨流失的药剂,其用量有效减小牙骨质-牙轴质接面与牙槽骨嵴之间的距离,其中所述抗骨硬化蛋白抗体的剂量任选地为每周约5mg至约1,000mg。
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