体内递送成骨诱导性制剂的聚合物包裹物的制作方法

专利名称：体内递送成骨诱导性制剂的聚合物包裹物的制作方法
技术领域：
本发明涉及一种聚合物包裹物(polymeric wrap)，它被设计成能够覆盖矫形外科装置并在体内对植入附近的组织提供成骨诱导性制剂。可在植入装置之前或在将装置植入患者的同时将聚合物包裹物施加于矫形外科装置。在本发明的一个实施方式中，以覆盖矫形装置外部形状的预成形组合物的形式提供包裹物。在本发明另一个实施方式中，聚合物包裹物包括多个聚合物层或由多个聚合物层构成，各个聚合物层包含不同的成骨诱导剂和/或不同浓度的成骨诱导剂。或者，聚合物包裹物的多个聚合物层具有不同的降解速率，从而以由特定聚合物的降解速率所指定的不同速率释放成骨诱导剂。
背景技术：
在美国，每年要对需要生物医学植入物的患者进行数以千计的植入手术。例如，仅在美国每年就进行了168,000例以上的全髋关节置换手术。Shindle，M.等，BioMechanics，11(2)22-32(2004)。
不幸的是，每年有许多植入外科手术需要修复手术来校正植入装置发生的缺陷。例如，如Croci等关于骨肿瘤的分段切除术的论述，骨肿瘤切除术后患者存活率的增加导致更需要进行植入装置的修复手术，而过去由于不成功的肿瘤控制不常出现上述结果。Croci等，Rev.Hosp.Clin.Fac.Med.S.Paulo，55(5)169-176(2000)。
设计成能够将成骨诱导剂递送至肌骨骼植入装置附近的装置尤其适用于初次手术和修复手术，用于防止植入装置附近骨质溶解的发生。这种性质的装置也可用于避免以后进行修复手术。设计成能够将成骨诱导剂递送至肌骨骼植入物附近的装置尤其适用于诸如以下手术的初次手术和修复手术肱骨元件柄(stem)的肩关节手术；肱骨和尺骨元件柄的肘关节手术；尺骨元件柄的腕关节手术；与髋臼杯(acetabular cup)植入物相关和与接骨螺钉相关的股骨柄的髋关节手术；股骨柄、股骨元件关节背侧、胫骨柄、胫骨盘下侧以及髌骨背侧的膝关节手术；以及全肩、全髋和全膝置换术。
发明概述因此，本领域仍然需要与矫形装置一起植入并提供成骨诱导性制剂以立即方式或在延长的时间范围内速释或缓释的成骨诱导性制剂。申请人在本文中描述了生物医学植入物装置的优选覆盖物(covering)，能够满足本领域对在矫形外科植入物装置植入部位附近提供成骨诱导性制剂的覆盖物的需要。
本发明的一个实施方式提供了一种聚合物包裹物，它包含至少两个可生物降解的聚合物片层，其中，所述至少两个可生物降解的聚合物片层相互结合，所述多层聚合物包裹物还包含至少一种成骨诱导性制剂。
本发明另一个实施方式提供了一种预防或治疗植入患者发生溶骨性病变的方法，该方法包括将含有成骨诱导性制剂的聚合物包裹物植入所述患者中。本发明另一个实施方式包括含有上述聚合物包裹物的成套工具。
通过阅读下面的详细说明，本领域技术人员容易明白本发明实施方式的这些和其它特征。
附图简要说明

图1A-B显示了一种施用于股骨柄植入物的聚合物包裹物。如图1A所示，将包裹物设计成套筒，以在植入之前覆盖矫形外科装置的外表面。如图1B所示，植入之前包裹物贴合在矫形外科装置的外部。
图2A-B显示了一种被设计成覆盖髋臼杯暴露面的聚合物包裹物。如图1A所示，将包裹物设计成髋臼杯形状。如图1B所示，植入之前聚合物包裹物基本上覆盖髋臼杯的外部。包裹物可任选地被有助于将该髋臼杯固定于内源性骨的物品穿刺，例如设计用于固定植入物的骨或其它螺钉。
优选实施方式的详细描述为了促进对本发明的理解，现在将参考优选实施方式并用具体语言来描述这些实施方式。本文所用的术语仅仅是为了描述具体实施方式
，而不旨在限制本发明的范围。除非文中清楚地另有说明，本说明书通篇所用单数形式“一种”、“一个”和“这个”包括复数涵义。因此，例如，“一个植入物”包括多个植入物以及单个植入物，“一种成骨诱导剂”表示一种或多种诱导剂以及本领域技术人员已知的等价形式，等等。
除非另有说明，本文所用的所有科技术语具有与本发明所属领域技术人员通常所理解相同的含义。虽然可使用类似于或等价于本文所述的任何方法和材料来实施或测试本发明，但现在将描述优选的方法、装置和材料。本文提及的所有出版物的引用是为了描述和说明出版物中报道的并且可与本发明联用的各种植入物、成骨诱导剂和其它部件。所有这些都不应解释为承认本发明没有居于这些现有技术的内容之前的新颖性。
如本文所用，“可生物利用的”指在患者体内提供成骨诱导剂时，所述成骨诱导剂能够保留生物活性。保留生物活性表示与植入之前的成骨诱导剂活性相比，成骨诱导剂保留至少25％，优选至少50％，更优选至少75％，最优选至少95％或更多的成骨诱导剂活性。
如本文所用，“成熟多肽”指多肽的翻译后加工形式。例如，宿主表达系统中表达后，成熟多肽可缺少一个或多个信号肽、前肽原和前肽结构域。生物领域技术人员明白信号肽、前肽原和前肽结构域的含义。
如本文所用，“速释”表示在相当短的时间内提供成骨诱导性制剂的本发明制剂。
如本文所用，“缓释”指被设计成在延长的时间范围内以可生物利用的形式提供相对恒定浓度的成骨诱导性制剂的本发明制剂。
如本文所用，“可生物降解的”指体内应用期间降解的聚合物。在本发明的一个实施方式中，聚合物降解产生聚合物单体亚单元。
如本文所用，“聚合物包裹物”指包括一个或多个聚合物层、或者由一个或多个聚合物层构成的片层，各个聚合物层任选地包含一种或多种成骨诱导剂，其中，所述成骨诱导剂以类似或不同的浓度存在于多个聚合物层中。如果聚合物包裹物包含多个聚合物层或由多个聚合物层构成，多个聚合物层可分别产生并组合，以形成聚合物包裹物。
如本文所用，“矫形外科装置”指经外科手术引入患者的任何生物医学植入物，可设计成与骨骼系统或身体关节联合起作用。
本发明实施方式包括聚合物包裹物，多层聚合物包裹物优选包含至少两个可生物降解的聚合物片层。所述至少两个可生物降解的聚合物片层优选相互结合，所述多层聚合物包裹物还包含至少一种成骨诱导性制剂。
本发明成骨诱导性制剂优选包含一种或多种诱导内源性骨、或与内源性骨相关的组织如结缔组织和血管组织生长的成骨诱导剂。此外，提供用于抑制骨再吸收的成骨诱导剂。成骨诱导性制剂包含成骨诱导剂，例如一种或多种骨形态发生蛋白(BMP)、一种或多种结缔组织生长因子(CTGF)、一种或多种血管内皮生长因子(VEGF)、护骨蛋白(OPG)、Periostin以及一种或多种转化生长因子-β(TGF-β)多核苷酸和多肽。聚合物包裹物中提供的成骨诱导剂是可生物利用的形式，它是速释或缓释制剂的组成成分。
在本发明的一个实施方式中，聚合物包裹物包含可生物降解的聚合物，它基于含成骨诱导性制剂的可生物降解的聚合物的降解速率释放成骨诱导性制剂。本发明还提供了预防和治疗患者矫形外科植入物附近溶骨性病变形成的方法。本发明也提供了增加植入部位周围组织生长的方法。
本发明包括聚合物包裹物，其包含能促进内源性骨、结缔组织和血管组织生长以及防止骨再吸收的成骨诱导性制剂。本发明中使用的成骨诱导性制剂包含一种或多种成骨诱导剂。成骨诱导性制剂可掺入形成聚合物包裹物的聚合物组合物中。或者，可在植入之前将成骨诱导性制剂施加在聚合物包裹物的外表面上。
在本发明的一个实施方式中，将聚合物包裹物中使用的成骨诱导性制剂与缓释聚合物混合，并模塑成预成形固体聚合物包裹物。可采用模具形成固体聚合物包裹物，过程是将液体聚合物加入到模具中，然后将聚合物溶液固化或固定形成预成形聚合物片层。优选地，可通过增加聚合物的抗生物降解性，例如通过引入或增加可生物降解的聚合物组合物中所含生物稳定聚合物的百分比来操纵成骨诱导剂从聚合物包裹物缓慢释放的持续时间。
在本发明另一优选实施方式中，聚合物包裹物由在植入之前单独施加在矫形外科装置上的任选预成形的一层或多层聚合物组成。所述在植入之前施加在矫形外科装置上的一层或多层可用于形成与矫形外科装置一起植入的多层聚合物包裹物。任选地，配制多层包裹物的各个聚合物层，使其具有不同的降解特征。使用具有不同降解速率的多层聚合物包裹物使本领域技术人员能够构建具有定制降解特征的聚合物包裹物。
例如，如果患者在初始相需要大剂量成骨诱导剂并在延长的时间段内需要持续浓度的成骨诱导剂，则可将多层包裹物配制成在具有高生物降解速率的聚合物外层中含有高浓度成骨诱导剂，从而在开始时释放高浓度成骨诱导剂，以及含有成骨诱导剂和低降解速率的一个或多个聚合物内层。或者，如果确定患者将受益于延长的成骨诱导剂释放持续时间，可将多层聚合物包裹物配制成任选地含有成骨诱导剂的一个或多个可生物降解的聚合物外层和含有体内生物降解速率降低的成骨诱导剂的一个或多个可生物降解的聚合物内层。这样，聚合物包裹物可提供相对持续的成骨诱导剂来源。所述多层聚合物包裹物可包含引入聚合物包裹物的成骨诱导性制剂中的一种或多种成骨诱导剂。
在本发明另一个实施方式中，多层聚合物包裹物包含至少一种成骨诱导剂或由至少一种成骨诱导剂组成，它们在这个聚合物包裹物的各个聚合物层中浓度不同。例如，多层可生物降解的聚合物包裹物的一个或多个内层可包含较高浓度的成骨诱导剂，而可生物降解的聚合物包裹物的一个或多个外层可包含较低浓度的成骨诱导剂。在该实施方式中，浓度平稳增加的成骨诱导剂被引入患者体内。或者，当成骨诱导剂在体内随着时间推移活性降低时，含较高浓度成骨诱导剂的聚合物包裹物内层将有助于补偿内层内层中一种或多种成骨诱导剂的活性降低，从而在可生物降解的聚合物包裹物的整个使用寿命期间提供相对恒定浓度的成骨诱导剂(活性方面)。换言之，多层聚合物包裹物内层中较高浓度的成骨诱导剂可补偿可生物利用的活性成骨诱导剂随时间推移的浓度降低。
本发明另一方面涉及掺入聚合物包裹物中的成骨诱导性制剂。成骨诱导性制剂优选包含一种或多种成骨诱导剂，并提供作为速释或缓释制剂的一种或多种可生物利用形式的试剂。成骨诱导性制剂还任选地包含一种或多种以下成分抗生素、载体、骨髓抽吸物、骨髓浓缩物、脱矿物质骨基质、免疫抑制剂、提高等张性(isotonicity)和化学稳定性的试剂、以及一种或多种(包括所有)所述成分的组合。
本发明实施方式的成骨诱导性制剂可以是速释制剂或缓释制剂。植入外科领域技术人员能根据诸如年龄和身体活动水平等因素确定患者适合速释制剂或是缓释制剂。因此，本发明成骨诱导性制剂可以是速释制剂、缓释制剂或二者兼有。
代表性的速释制剂是液体制剂，它包含施加在聚合物包裹物表面的至少一种成骨诱导剂。液体制剂提供可生物利用形式的成骨诱导剂，以液体制剂的流体性质如在植入部位的扩散速率、内源性流体的影响等确定的速率释放。合适的液体制剂的例子包含水、盐水或不会诱导宿主免疫反应的其它可接受的流体介质。
本发明速释制剂提供在相当短的时间内释放的成骨诱导性制剂，虽然诸如体液亲近性(proximity)、制剂组成等因素将影响成骨诱导性从制剂的释放时间。但是，速释制剂被设计成不能在延长的时间段内保留一种或多种成骨诱导剂，并且通常缺少作为速释制剂的组成成分的可生物降解的聚合物。
在本发明另一个实施方式中，成骨诱导性制剂可以是缓释制剂，它在延长的时间范围内提供可生物利用形式的成骨诱导性制剂。缓释制剂的释放持续时间由制剂的性质和上述其它因素如体液亲近性、以及制剂施用密度、含成骨诱导性制剂的可生物降解聚合物的降解速率和其它因素决定。然而，缓释制剂被设计成可在延长的时间范围内提供可生物利用形式的浓度相对恒定的制剂中的成骨诱导剂。聚合物包裹物中使用的可生物降解的缓释聚合物是本领域已知的，包括但不限于聚丙交酯、聚乙交酯、聚己酸内酯、聚酐、聚酰胺、聚氨酯、聚酯酰胺、聚原酸酯、聚二烷酮、聚缩醛、聚缩酮、聚碳酸酯、聚原碳酸酯、聚膦腈、聚羟基丁酸酯、聚羟基戊酸酯、聚亚烷基草酸酯、聚亚烷基琥珀酸酯、聚(苹果酸)、聚(氨基酸)、聚乙烯吡咯烷酮、聚乙二醇、聚羟基纤维素、壳多糖、壳聚糖、聚(L-乳酸)、聚(丙交酯-共-乙交酯)、聚(羟基丁酸酯-共-戊酸酯)以及上述材料的共聚物、三聚物、或者它们的组合或混合物。可生物降解聚合物的释放特征还可通过掺入能够影响聚合物组合物生物降解速率的生物稳定聚合物进行调整。可掺入可生物降解聚合物从而影响生物降解速率的生物稳定聚合物包括但不限于硅氧烷、聚酯、乙烯基均聚物和共聚物、丙烯酸酯均聚物和共聚物、聚醚以及纤维素类。
可生物降解的聚合物可以是固体形式的聚合物或者可以是施加后在适当时间内固化的液体聚合物。合适的液体聚合物制剂包括但不限于诸如美国专利5,744,153、4,938,763、5,278,201和5,278,202中所述的聚合物组合物，它们的全部内容参考包括在此。这些专利描述了能够用作控释药物组合物或用作植入物的液体聚合物组合物。该液体预聚物具有至少一个可聚合的烯键式不饱和基团(例如，丙烯酸-酯-封端的预聚物)。若采用固化剂，通常在临用前将固化剂加入到组合物中。在固化或固定预聚物之前将成骨诱导剂加入到液体预聚物中。引入固化剂之后，预聚物在短时间内保持液体状态。然后，混合物固化形成固体组合物。可将液体聚合物组合物以液体形式给予患者，然后在引入部位固化或固定形成固体聚合物涂覆组合物。或者，可将液体聚合物注入预成形模具中以形成聚合物包裹物，在植入患者之前预成形以贴合在矫形外科装置的外形上。考虑了聚合物的可生物降解形式，也考虑了能够影响聚合物生物降解速率的可生物降解聚合物和生物稳定聚合物的混合物。
本发明成骨诱导性制剂还考虑使用在延长的时间段内保持成骨诱导剂稳定性的水性或非水性肽制剂。用于长期稳定成骨诱导剂的水性和非水性制剂的非限制性例子包括美国专利5,916,582、5,932,547和5,981,489提供的制剂，它们各自的内容参考包括在此。
将一定量液体缓释聚合物组合物例如通过喷雾、涂抹或喷溅分配到聚合物包裹物上，给予后液体制剂固化形成缓释制剂。
在本发明另一个实施方式中，用于体内递送成骨诱导性制剂的液体组合物包含成骨诱导剂与不溶于水的生物相容性聚合物的偶联物，所得聚合物活性物质偶联物在生物相容性溶剂中溶解形成液体聚合物体系。此外，液体聚合物体系还可包含不与成骨诱导剂偶联的不溶于水的生物相容性聚合物。在本发明的一个实施方式中，这些液体组合物可以液体形式引入对象体内。然后，液体组合物在原位固化或凝固成控释植入物，其中成骨诱导剂偶联于固体基质聚合物。
可以在成骨诱导性制剂中作为分离的多肽或多核苷酸给予本发明实施方式的成骨诱导剂。分离的成骨诱导剂的多核苷酸组成包括但不限于骨形态发生蛋白(BMP)、血管内皮生长因子(VEGF)、结缔组织生长因子(CTGF)、护骨蛋白、Periostin和转化生长因子β(TGF-β)多核苷酸。成骨诱导剂的多核苷酸组成包括但不限于携带编码感兴趣成骨诱导性多肽的多核苷酸的基因治疗载体。基因治疗方法需要可操作地连接或结合于启动子和靶组织表达成骨诱导性多肽所需的任何其它遗传元件的编码成骨诱导性多肽的多核苷酸。这些基因疗法和递送技术是本领域已知的，例如参见国际公开号WO90/11092，其内容参考包括在此。合适的基因治疗载体包括但不限于，不整合入宿主基因组的基因治疗载体。或者，合适的基因治疗载体包括但不限于，整合入宿主基因组的基因治疗载体。
在一个实施方式中，以质粒制剂的形式递送本发明多核苷酸。质粒DNA或RNA制剂指不含辅助、促进或有助于进入细胞的任何递送运载体的编码成骨诱导性多肽的序列，包括病毒序列、病毒颗粒、脂质体制剂、lipofectin或沉淀剂等。任选地，本发明基因治疗组合物可以脂质体制剂和lipofectin制剂的形式递送，这些制剂可通过本领域技术人员熟知的方法制备。一般方法参见，例如美国专利5,593,972、5,589,466和5,580,859，其内容参考包括在此。
基因治疗载体还包括合适的腺病毒载体，包括但不限于Kozarsky和Wilson，Curr.Opin.Genet.Devel.，3499-503(1993)；Rosenfeld等，Cell，68143-155(1992)；Engelhardt等，Human Genet.Ther.，4759-769(1993)；Yang等，Nature Genet.，7362-369(1994)；Wilson等，Nature，365691-692(1993)；和美国专利5,652,224所述的载体，其内容参考包括在此。
分离的成骨诱导剂的多肽组成包括但不限于分离的骨形态发生蛋白(BMP)、血管内皮生长因子(VEGF)、结缔组织生长因子(CTGF)、护骨蛋白、Periostin和转化生长因子β(TGF-β)多肽。成骨诱导剂的多肽组成包括但不限于分离的全长蛋白质、蛋白质片段或变体。在本发明一个优选的实施方式中，成骨诱导剂多肽片段包含分离的全长多肽的前肽形式或由其构成。在本发明一个尤其优选的实施方式中，成骨诱导剂的多肽片段包含分离的全长多肽的成熟形式或由其构成。还优选编码成骨诱导剂的前肽和成熟多肽的多核苷酸。
本发明成骨诱导剂的变体包括但不限于设计成在体内增加成骨诱导剂活性持续时间的蛋白质变体。变体成骨诱导剂的优选实施方式包括但不限于偶联于聚乙二醇(PEG)部分以增加其体内半衰期(也称为聚乙二醇化)的全长蛋白质或其片段。聚乙二醇化多肽的方法是本领域众所周知的(例如，参见美国专利6,552,170和欧洲专利0,401,384，作为制备聚乙二醇化多肽的方法的例子)。
在本发明另一个实施方式中，提供的成骨诱导剂是成骨诱导性制剂中的融合蛋白。在一个实施方式中，成骨诱导剂是具有人IgG的Fc部分的融合蛋白。在本发明另一个实施方式中，本发明成骨诱导剂是异源二聚体或同源二聚体或多聚体。优选的融合蛋白的例子包括但不限于成熟成骨诱导性多肽和人免疫球蛋白G(IgG)的Fc部分的配体融合物。制备融合蛋白和编码其的构建物的方法本领域众所周知的。
包含在成骨诱导性制剂中的本发明成骨诱导剂是无菌的。在一个非限制性方法中，例如通过滤过除菌滤膜(例如，0.2微米膜或滤器)可容易地实现灭菌。
在本发明的一个实施方式中，提供的聚合物包裹物在包裹物内不包含成骨诱导性制剂。在本发明该实施方式中，在将包裹物植入患者之前将成骨诱导性制剂引入聚合物包裹物的表面。或者，将成骨诱导性制剂加到多层聚合物包裹物的可生物降解的聚合物片层之间。在这种情况下，通常将成骨诱导剂加入具有无菌入口的容器中，例如具有可用皮下注射针刺穿的塞子的静脉输液袋或瓶。在一个实施方式中，将成骨诱导剂和制备的成骨诱导性制剂以水溶液或以可重建冻干制剂的形式储存在独立的容器中，例如密封安瓿或小瓶。作为冻干制剂的一个例子，在10毫升小瓶中加入5毫升过滤除菌的1％(w/v)成骨诱导剂水溶液，然后冻干所得混合物。在以合适的溶液形式施加之前，通过重建冻干试剂制备成骨诱导剂，与制备的成骨诱导性制剂混合后，在植入患者之前或同时施加在聚合物包裹物的表面或施加在多层聚合物包裹物的聚合物层之间。通过将聚合物包裹物浸入成骨诱导性制剂中，将成骨诱导性制剂喷涂在聚合物包裹物的表面上，或通过任何其它施加方式来完成施加。
本领域技术人员将理解，成骨诱导剂的浓度可根据所需的成骨诱导长度或程度而变化。类似地，本领域技术人员将理解，可通过操纵含缓释制剂的组成，例如调节缓释聚合物中生物稳定聚合物的百分比，来调节缓释持续时间。
提供可用于形成体内递送成骨诱导剂的聚合物片层的液体组合物的方法是将活性物质与不溶于水的生物相容性聚合物偶联并将所得聚合物-活性物质偶联物溶解在生物相容性溶剂中，形成类似于美国专利4,938,763、5,278,201和5,278,202中所述的液体聚合物体系。不溶于水的生物相容性聚合物可以是上述专利中所述的聚合物或相关共聚物。此外，液体聚合物体系还可包含没有偶联活性物质的不溶于水的生物相容性聚合物。在本发明的一个实施方式中，这些液体组合物可以液体形式引入对象体内。然后在原位固化或凝固液体组合物以形成控释植入物，其中活性物质偶联于固体基质聚合物。
本发明成骨诱导性制剂任选地还可任选地包含脱矿物质骨基质组合物(后文中称为“DBM”组合物)、骨髓抽吸物、骨髓浓缩物、或这些物质的组合或排列。制备DBM的方法是本领域众所周知的，DBM可根据O′Leary等(美国专利5,073,373)的内容获得，或者(例如)以AlloGro从供应商如AlloSource(Centennial，CO)购得。获得骨髓抽吸物的方法及有利于提取骨髓抽吸物的装置是本领域众所周知的，例如参见Turkel等的美国专利5,257,632。
本发明成骨诱导性制剂任选地还包含可与成骨诱导剂一起给予的抗生素。如Vehmeyer等所述，由于引入了来自活体供者的受污染的同种异体移植物组织，存在发生细菌污染的可能性。Vehmeyer，SB等，Acta Orthop Scand.，73(2)165-169(2002)。本发明抗生素也可与成骨诱导性制剂共同给予以防止植入手术期间引入患者的专性病原体或机会病原体感染。
本发明成骨诱导性制剂中使用的抗生素包括但不限于阿莫西林、β-内酰胺酶、氨基糖苷类、β-内酰胺(糖肽)、克林霉素、氯霉素、头孢菌素、环丙沙星、红霉素、氟喹诺酮类、大环内酯类、甲硝唑、青霉素类、喹诺酮类、雷帕霉素、利福平、链霉素、磺胺、四环素类、甲氧苄啶、甲氧苄啶-磺胺甲唑和万古霉素。此外，由于医院感染或进行外科手术的场所的其它特异性因素，植入外科领域技术人员或进行植入手术的场所的管理者偏爱引入一种或多种上述抗生素。因此，本发明还考虑，本发明成骨诱导性制剂中可包含一种或多种本文所述抗生素以及一种或多种这些抗生素的任意组合。
本发明成骨诱导性制剂任选地还包含免疫抑制剂，尤其是将同种异体移植物组合物给予患者的情况下。可与本发明成骨诱导性制剂联合给予的合适的免疫抑制剂包括但不限于类固醇、环孢霉素、环孢霉素类似物、环磷酰胺、甲基泼尼松、泼尼松、硫唑嘌呤、FK-506、15-脱氧精胍菌素、以及通过抑制效应T细胞功能起作用的其它免疫抑制剂。可与本发明成骨诱导性制剂联合给予的其它免疫抑制剂包括但不限于泼尼松龙、甲氨蝶呤、沙利度胺、甲氧沙林、雷帕霉素、来氟米特、咪唑立宾(布累迪宁TM)、布喹那、脱氧精胍菌素和azaspirane(SKF105685)、Orthoclone OKTTM3(莫罗单抗-CD3)、SandimmuneTM、NeoralTM、SangdyaTM(环孢霉素)、PrografTM(FK506、他克莫司)、CellceptTM(麦考酚酸吗乙酯，其活性代谢物是麦考酚酸)、ImuranTM(硫唑嘌呤)、糖皮质激素、肾上腺皮质类固醇如DeltasoneTM(泼尼松)和HydeltrasolTM(泼尼松龙)、FolexTM和MexateTM(甲氨蝶呤)、Oxsoralen-UltraTM(甲氧沙林)和RapamuenTM(西罗莫司)。
本发明成骨诱导性制剂任选地还包含，运载体如水、盐水、林格溶液、磷酸钙基载体或右旋糖溶液。本文中也可使用非水性运载体如非挥发性油和油酸乙酯，以及脂质体。
在本发明的一个实施方式中，胶原可用作载体或作为用作递送成骨诱导性制剂的聚合物包裹物的基质。在本发明另一个实施方式中，将胶原与糖胺聚糖联合用作成骨诱导性制剂的载体，如美国专利5,922,356所述，其内容参考包括在此。制剂中糖胺聚糖的含量优选小于40％的制剂重量，更优选1-10重量％。胶原优选占20-95％的制剂重量，更优选40-60重量％。
任何胶原均可用作成骨诱导性制剂的载体。可用作载体的合适的胶原的例子包括但不限于I型人胶原、II型人胶原、III型人胶原、IV型人胶原、V型人胶原、VI型人胶原、VII型人胶原、VIII型人胶原、IX型人胶原、X型人胶原、XI型人胶原、XII型人胶原、XIII型人胶原、XIV型人胶原、XV型人胶原、XVI型人胶原、XVII型人胶原、XVIII型人胶原、XIX型人胶原、XXI型人胶原、XXII人胶原型、XXIII型人胶原、XXIV型人胶原、XXV型人胶原、XXVI型人胶原、XXVII型人胶原和XXVIII人胶原型以及它们的组合。可用于本发明的胶原载体还包含任何上述胶原类型的异源和同源三聚体或由其构成。在本发明一个优选的实施方式中，胶原载体包含I型人胶原、II型人胶原和III型人胶原的异源或同源三聚体或其组合，或者由其构成。
在本发明另一个实施方式中，上述胶原基本上组成了聚合物包裹物。例如，形成聚合物包裹物的胶原掺入了包含一种或多种成骨诱导剂的成骨诱导性制剂。将含有至少一种成骨诱导剂的胶原包裹物引入患者，植入时包裹物基本上覆盖矫形外科装置。植入后，胶原包裹物释放含有成骨诱导剂的成骨诱导性制剂。有用的胶原包裹物的例子包括但不限于胶原片层和牛源性重组胶原片层。在本发明另一个实施方式中，胶原包裹物被一种或多种可生物降解的聚合物层所覆盖，从而形成不同的多层聚合物片材。
用作聚合物包裹物载体的胶原可以是人或非人源性的，重组或非重组的。在本发明一个优选的实施方式中，用作载体的胶原是重组胶原。制备重组胶原的方法是本领域已知的，例如，利用诸如美国专利5,895,833(转基因生产)，J.Myllyharju等，Biotechnology of Extracellular Matrix，353-357(2000)(在巴斯德毕赤酵母中产生重组人I-III型(production of recombinant human types I-III inPichia pastoris))，Wong Po Foo，C.等，Adv.Drug Del.Rev.，541131-1143(2002)，或Toman，P.D.等，J.Biol.Chem.，275(30)23303-23309(2001)等所述的重组方法，上述文献的内容参考包括在此。或者，例如从FibroGen(San Francisco，California)购得重组人胶原类型。
本发明成骨诱导性制剂还任选地包含提高等张性和化学稳定性的物质。这些物质在所用剂量和浓度下对患者无毒，并包括缓冲剂，例如磷酸盐、柠檬酸盐、琥珀酸盐、醋酸以及其它有机酸或其盐；抗氧化剂，例如抗坏血酸；小分子量(小于约10个残基)多肽，例如多聚精氨酸或三肽；蛋白质，例如血清白蛋白、明胶或免疫球蛋白类；氨基酸，例如甘氨酸、谷氨酸、天冬氨酸或精氨酸；单糖、二糖和其它碳水化合物，包括纤维素或其衍生物、葡萄糖、甘露糖或糊精；螯合剂，例如EDTA；糖醇，例如甘露醇或山梨糖醇；抗衡离子，例如钠；和/或非离子型表面活性剂如聚山梨酯、泊洛沙姆或PEG。
本发明成骨诱导性制剂还包含分离的成骨诱导剂。分离的成骨诱导剂可促进内源性骨生长，或有助于防止植入物周围骨组织被破骨细胞再吸收。本发明分离的成骨诱导剂是多肽或多核苷酸形式。本发明分离的成骨诱导剂包括全长蛋白质及其片段、以及本文所提供的分离的成骨诱导剂的多肽变体或突变体。
在本发明另一个实施方式中，成骨诱导剂多肽是异源二聚体或同源二聚体，以及多聚体或其组合。
重组表达的蛋白质可以是天然形式、截短类似物、突变蛋白、融合蛋白、以及能够诱导骨、软骨或其它类型的组织形成的其它构建形式，如体外或离体生物测定和体内植入哺乳动物(包括人)所显示的那样。
本发明还考虑使用与本文提供的分离的成骨诱导剂多核苷酸和多肽具有至少95％同源、更优选97％、甚至更优选99％同源的多核苷酸和多肽。典型的成骨诱导性制剂包含在pH约3-8下，浓度约为0.1-100毫克/毫升、优选1-10毫克/毫升的分离的成骨诱导剂。
在本发明一个实施方式中，分离的成骨诱导剂包含骨形态发生蛋白(“BMP”)家族成员的一种或多种多核苷酸或多肽。BMP是一类认为对内源性骨组织具有成骨诱导活性或促进生长活性的蛋白质。BMP家族已知成员包括但不限于BMP-1、BMP-2、BMP-3、BMP-4、BMP-5、BMP-6、BMP-7、BMP-8、BMP-9、BMP-10、BMP-11、BMP-12、BMP-13、BMP-15、BMP-16、BMP-17和BMP-18。
可用作分离的成骨诱导剂的BMP包括但不限于以下BMP对应于SEQ ID NO1、SEQ ID NO2、SEQ ID NO3和SEQ ID NO4的BMP-1多核苷酸和多肽，以及成熟BMP-1多肽和编码它的多核苷酸；对应于SEQ ID NO5和SEQ ID NO66的BMP-2多核苷酸和多肽，以及成熟BMP-2多肽和编码它的多核苷酸；对应于SEQ ID NO7和SEQ ID NO8的BMP-3多核苷酸和多肽，以及成熟BMP-3多肽和编码它的多核苷酸；对应于SEQ ID NO9和SEQ ID NO10的BMP-4多核苷酸和多肽，以及成熟BMP-4多肽和编码它的多核苷酸；对应于SEQ ID NO11、SEQ ID NO12、SEQ ID NO13和SEQ ID NO14的BMP-5多核苷酸和多肽，以及成熟BMP-5多肽和编码它的多核苷酸；对应于SEQ ID NO15、SEQ ID NO16、SEQ ID NO17和SEQ ID NO18的BMP-6多核苷酸和多肽，以及成熟BMP-6多肽和编码它的多核苷酸；对应于SEQ ID NO19、SEQ ID NO20、SEQ ID NO21和SEQ ID NO22的BMP-7多核苷酸和多肽，以及成熟BMP-7多肽和编码它的多核苷酸；对应于SEQ ID NO23、SEQ ID NO24、SEQ ID NO25和SEQ ID NO26的BMP-8多核苷酸和多肽，以及成熟BMP-8多肽和编码它的多核苷酸；对应于SEQ ID NO27和SEQ ID NO28的BMP-9多核苷酸和多肽，以及成熟BMP-9多肽和编码它的多核苷酸；
对应于SEQ ID NO29、SEQ ID NO30、SEQ ID NO31和SEQ ID NO32的BMP-10多核苷酸和多肽，以及成熟BMP-10多肽和编码它的多核苷酸；对应于SEQ ID NO33和SEQ ID NO34的BMP-11多核苷酸和多肽，以及成熟BMP-11多肽和编码它的多核苷酸；对应于SEQ ID NO35和SEQ ID NO36的BMP-12多核苷酸和多肽，以及成熟BMP-12多肽和编码它的多核苷酸；对应于SEQ ID NO37和SEQ ID NO38的BMP-13多核苷酸和多肽，以及成熟BMP-13多肽和编码它的多核苷酸；对应于SEQ ID NO39、SEQ ID NO40、SEQ ID NO41和SEQ ID NO42的BMP-15多核苷酸和多肽，以及成熟BMP-15多肽和编码它的多核苷酸；对应于SEQ ID NO43、SEQ ID NO44、SEQ ID NO45和SEQ ID NO46的BMP-16多核苷酸和多肽，以及成熟BMP-16多肽和编码它的多核苷酸；对应于SEQ ID NO47和SEQ ID NO48的BMP-17多核苷酸和多肽，以及成熟BMP-17多肽和编码它的多核苷酸；和对应于SEQ ID NO49和SEQ ID NO50的BMP-18多核苷酸和多肽，以及成熟BMP-18多肽和编码它的多核苷酸。
用作本发明成骨诱导剂的BMP包括或由以下一种或多种物质构成BMP-1；BMP-2；BMP-3；BMP-4；BMP-5；BMP-6；BMP-7；BMP-8；BMP-9；BMP-10；BMP-11；BMP-12；BMP-13；BMP-15；BMP-16；BMP-17；和BMP-18；以及一种或多种这些BMP、包括全长BMP或其片段的任意组合，，或者它们的组合，它可以是多肽形式或是编码所有所述BMP的多肽片段的多核苷酸形式。分离的BMP成骨诱导剂可以多核苷酸、多肽或两者组合的形式给予。
在本发明一个尤其优选的实施方式中，分离的成骨诱导剂包括或由BMP-2多核苷酸或多肽或其成熟片段构成。
在本发明另一个实施方式中，分离的成骨诱导剂包含破骨细胞生成抑制剂，以抑制植入物植入部位周围的骨组织被破骨细胞再吸收。
破骨细胞和破骨细胞生成抑制剂包括但不限于对应于SEQ ID NO51、SEQ ID NO52、SEQ ID NO53和SEQ ID NO54的护骨蛋白多核苷酸和多肽，以及成熟护骨蛋白多肽和编码它的多核苷酸。护骨蛋白是TNF-受体超家族的成员，是用作骨再吸收负调节物的成骨细胞分泌的诱杀受体。这种蛋白特异性结合于其配体，即护骨蛋白配体(TNFSF11/OPGL)，它们都是破骨细胞形成的关键性细胞外调节物。
破骨细胞生成抑制剂还包括但不限于化合物如二膦酸盐(bisphosphonate)、5-脂肪氧合酶抑制剂如美国专利5,534,524和6,455,541所述(其内容参考包括在此)，杂环化合物如美国专利5,658,935所述(其内容参考包括在此)，2，4-二氧代咪唑烷和咪唑烷衍生物如美国专利5,397,796和5,554,594所述(其内容参考包括在此)，磺胺衍生物如美国专利6,313,119所述(其内容参考包括在此)，和酰基胍化合物如美国专利6,492,356所述(其内容参考包括在此)。
在本发明另一个实施方式中，分离的成骨诱导剂包括结缔组织生长因子(“CTGF”)家族成员的一种或多种多核苷酸或多肽。CTGF是一类认为对结缔组织具有生长促进活性的蛋白质。已知的CTGF家族成员包括但不限于CTGF-1、CTGF-2和CTGF-4。
可用作分离的成骨诱导剂的CTGF包括但不限于以下CTGF对应于SEQ ID NO55、SEQ ID NO56、SEQ ID NO57和SEQ ID NO58的CTGF-1多核苷酸和多肽，以及成熟CTGF-1多肽和编码它的多核苷酸。
对应于SEQ ID NO59和SEQ ID NO60的CTGF-2多核苷酸和多肽，以及成熟CTGF-2多肽和编码它的多核苷酸。
对应于SEQ ID NO61和SEQ ID NO62的CTGF-4多核苷酸和多肽，以及成熟CTGF-4多肽和编码它的多核苷酸。
在本发明另一个实施方式中，分离的成骨诱导剂包括血管内皮生长因子(“VEGF”)家族成员的一种或多种多核苷酸或多肽。VEGF是一类认为对血管组织具有生长促进活性的蛋白质。已知的VEGF家族成员包括但不限于VEGF-A、VEGF-B、VEGF-C、VEGF-D和VEGF-E。
可用作成骨诱导剂的VEGF包括但不限于以下VEGF对应于SEQ ID NO63和SEQ ID NO64的VEGF-A多核苷酸和多肽，以及成熟VEGF-A多肽和编码它的多核苷酸。
对应于SEQ ID NO65和SEQ ID NO66的VEGF-B多核苷酸和多肽，以及成熟VEGF-B多肽和编码它的多核苷酸。
对应于SEQ ID NO67和SEQ ID NO68的VEGF-C多核苷酸和多肽，以及成熟VEGF-C多肽和编码它的多核苷酸。
对应于SEQ ID NO69和SEQ ID NO70的VEGF-D多核苷酸和多肽，以及成熟VEGF-D多肽和编码它的多核苷酸。
对应于SEQ ID NO71和SEQ ID NO72的VEGF-E多核苷酸和多肽，以及成熟VEGF-E多肽和编码它的多核苷酸。
在本发明另一个实施方式中，分离的成骨诱导剂包括转化生长因子β基因(“TGF-β”)的一种或多种多核苷酸或多肽。TGF-β是一类认为对多种组织包括结缔组织具有生长促进活性的蛋白质。已知的TGF-β家族成员包括但不限于TGF-β-1、TGF-β-2和TGF-β-3。
可用作分离的成骨诱导剂的TGF-β包括但不限于以下TGF-β对应于SEQ ID NO73、SEQ ID NO74、SEQ ID NO75和SEQ ID NO76的TGF-β-1多核苷酸和多肽，以及成熟TGF-β-1多肽和编码它的多核苷酸。
对应于SEQ ID NO77、SEQ ID NO78、SEQ ID NO79和SEQ ID NO80的TGF-β-2多核苷酸和多肽，以及成熟TGF-β-2多肽和编码它的多核苷酸。
对应于SEQ ID NO81和SEQ ID NO82的TGF-β-3多核苷酸和多肽，以及成熟TGF-β-3多肽和编码它的多核苷酸。
在本发明另一个实施方式中，分离的成骨诱导剂包括促进骨接合(adhesion)的多核苷酸和多肽，例如认为在骨形成中起接合分子作用的Periostin多核苷酸和多肽。
骨接合促进剂包括但不限于对应于SEQ ID NO83和SEQ ID NO84的Periostin多核苷酸和多肽，以及成熟Periostin多肽和编码它的多核苷酸。
在本发明另一个实施方式中，分离的成骨诱导剂包括以下任一蛋白家族中的一个或多个成员骨形态发生蛋白(BMP)、结缔组织生长因子(CTGF)、血管内皮生长因子(VEGF)、护骨蛋白或任何其它破骨细胞生成抑制剂、Periostin和转化生长因子-β(TGF-β)、以及这些成骨诱导剂的任意组合。
用于制备聚合物包裹物的聚合物包括能够形成生物学上可接受的可生物降解薄膜的任何聚合物。本发明聚合物包裹物包括一个或多个可生物降解的聚合物层，其中，所述可生物降解的聚合物层在聚合物层中任选地包含成骨诱导性制剂。在本发明的一个实施方式中，多层聚合物包裹物的制备过程如下合成含有一种或多种成骨诱导剂作为成骨诱导性制剂组分的至少两个独立的聚合物层；然后，例如通过将一个聚合物层铺在另外一层或多层上合并所述至少两个独立的聚合物层，形成多层聚合物包裹物。任选地，使用少量可生物降解的粘固剂或其它生物相容性粘合剂作为所述至少两个独立的聚合物层之间的粘合剂。
在本发明另一个实施方式中，在将下一聚合物层叠加到多层聚合物包裹物上之前，将成骨诱导性制剂施加到可生物降解的聚合物层的表面上。在该实施方式中，包含的成骨诱导性制剂是聚合物包裹物的至少两个独立的聚合物层之间的液体层。一旦一个或多个聚合物层降解，成骨诱导性制剂从聚合物包裹物中释放，以生物活性形式存在。
也可通过以下过程产生聚合物包裹物制备液体形式(预聚物)的一个或多个聚合物层并与成骨诱导性制剂混合，将预聚物液体施加到预成形模具中，固化或固定液体预聚物，形成预先形成贴合在矫形外科装置外形上的预成形聚合物包裹物。在该实施方式中，在植入患者之前或同时将预成形聚合物包裹物围绕在矫形外科装置的外形上。
在本发明一个可选的实施方式中，通过制备各个独立的可生物降解聚合物层来产生预成形多层聚合物包裹物，设计在植入患者之前将预成形层围绕在矫形外科装置的外形上。在该可选的实施方式中，将成骨诱导性制剂以液体制剂的形式施加在独立的预成形聚合物层之间。根据多层聚合物包裹物中独立的可生物降解聚合物外层的体内降解速率，从多层聚合物包裹物中释放生物活性形式的成骨诱导性制剂。
本发明还涉及含有本发明成骨诱导性多核苷酸的载体、宿主细胞、以及通过重组技术制备成骨诱导性多肽。载体可以是例如噬菌体、质粒、病毒或逆转录病毒载体。逆转录病毒载体可具有复制能力或是复制缺陷的。在后一种情况下，通常只有在补偿性宿主细胞中才发生病毒增殖。
多核苷酸可连接于含有可选标记的载体在宿主中增殖。通常，将质粒载体引入沉淀物如磷酸钙沉淀物，或与带电脂质形成复合物。若载体是病毒，可使用合适的包装细胞株进行体外包装，然后转导入宿主细胞。有用的载体包括但不限于质粒、噬菌体、昆虫和动物细胞载体、逆转录病毒、粘粒、以及其它单链和双链病毒。
多核苷酸插入物应可操作地连接于合适的启动子，例如噬菌体λPL启动子，大肠杆菌(E.Coli)lac、trp、phoA和tac启动子，SV40早期和晚期启动子以及逆转录病毒LTR的启动子等。其它合适的启动子是本领域技术人员已知的。表达构建物还包括转录起始位点、转录终止位点；复制序列起点、以及转录区中用于翻译的核糖体结合位点。构建物表达的转录物的编码部分优选包括开始处的翻译起始密码子和适当地位于待翻译多肽末端的终止密码子(UAA、UGA或UAG)。
表达构建物可还包含以下序列，例如增强子序列、有效RNA加工信号如剪接和聚腺苷酸化信号、提高翻译效率的序列以及增加蛋白质分泌的序列。
制备成骨诱导剂如重组蛋白或蛋白片段的表达系统和方法是本领域众所周知的。例如，采用细菌、昆虫或哺乳动物表达系统来制备重组蛋白或其片段的方法是本领域众所周知的(例如参见“分子生物技术重组DNA的原理和应用”(Molecular BiotechnologyPrinciples and Applications of Recombinant DNA)，B.R.Glick、J.Pasternak和M.M.Bendig，Genetic Engineering，7，第91-127页(1988)，关于重组蛋白制备的讨论)。
表达载体优选包括至少一个可选择标记。所述标记包括二氢叶酸还原酶、G418或新霉素。
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ccgaggtcat cacctcccag tacaacaaca tgcgcgtgga gttcaagtcc gacaacaccg 2100tgtccaaaaa gggcttcaag gcccacttct tctcagaaaa gaggccagct ctgcagcccc 2160ctcggggacg cccccaccag ctcaaattcc gagtgcagaa aagaaaccgg accccccagt 2220gaggcctgcc aggcctcccg gaccccttgt tactcaggaa cctcaccttg gacggaatgg 2280gatgggggct tcggtgccca ccaacccccc acctccactc tgccattccg gcccacctcc 2340ctctggccgg acagaactgg tgctctcttc tccccactgt gcccgtccgc ggaccgggga 2400cccttccccg tgccctaccc cctcccattt tgatggtgtc tgtgacattt cctgttgtga 2460agtaaaagag ggacccctgc gtcctgc 2487<210>2<211>730<212>PRT<213>智人(Homo sapiens)<400>2Met Pro Gly Val Ala Arg Leu Pro Leu Leu Leu Gly Leu Leu Leu Leu1 5 10 15Pro Arg Pro Gly Arg Pro Leu Asp Leu Ala Asp Tyr Thr Tyr Asp Leu20 25 30Ala Glu Glu Asp Asp Ser Glu Pro Leu Asn Tyr Lys Asp Pro Cys Lys35 40 45Ala Ala Ala Phe Leu Gly Asp Ile Ala Leu Asp Glu Glu Asp Leu Arg50 55 60Ala Phe Gln Val Gln Gln Ala Val Asp Leu Arg Arg His Thr Ala Arg65 70 75 80Lys Ser Ser Ile Lys Ala Ala Val Pro Gly Asn Thr Ser Thr Pro Ser85 90 95Cys Gln Ser Thr Asn Gly Gln Pro Gln Arg Gly Ala Cys Gly Arg Trp100 105 110Arg Gly Arg Ser Arg Ser Arg Arg Ala Ala Thr Ser Arg Pro Glu Arg115 120 125Val Trp Pro Asp Gly Val Ile Pro Phe Val Ile Gly Gly Asn Phe Thr130 135 140Gly Ser Gln Arg Ala Val Phe Arg Gln Ala Met Arg His Trp Glu Lys145 150 155 160His Thr Cys Val Thr Phe Leu Glu Arg Thr Asp Glu Asp Ser Tyr Ile165 170 175Val Phe Thr Tyr Arg Pro Cys Gly Cys Cys Ser Tyr Val Gly Arg Arg180 185 190Gly Gly Gly Pro Gln Ala Ile Ser Ile Gly Lys Asn Cys Asp Lys Phe
195 200 205Gly Ile Val Val His Glu Leu Gly His Val Val Gly Phe Trp His Glu210 215 220His Thr Arg Pro Asp Arg Asp Arg His Val Ser Ile Val Arg Glu Asn225 230 235 240Ile Gln Pro Gly Gln Glu Tyr Asn Phe Leu Lys Met Glu Pro Gln Glu245 250 255Val Glu Ser Leu Gly Glu Thr Tyr Asp Phe Asp Ser Ile Met His Tyr260 265 270Ala Arg Asn Thr Phe Ser Arg Gly Ile Phe Leu Asp Thr Ile Val Pro275 280 285Lys Tyr Glu Val Asn Gly Val Lys Pro Pro Ile Gly Gln Arg Thr Arg290 295 300Leu Ser Lys Gly Asp Ile Ala Gln Ala Arg Lys Leu Tyr Lys Cys Pro305 310 315 320Ala Cys Gly Glu Thr Leu Gln Asp Ser Thr Gly Asn Phe Ser Ser Pro325 330 335Glu Tyr Pro Asn Gly Tyr Ser Ala His Met His Cys Val Trp Arg Ile340 345 350Ser Val Thr Pro Gly Glu Lys Ile Ile Leu Asn Phe Thr Ser Leu Asp355 360 365Leu Tyr Arg Ser Arg Leu Cys Trp Tyr Asp Tyr Val Glu Val Arg Asp370 375 380Gly Phe Trp Arg Lys Ala Pro Leu Arg Gly Arg Phe Cys Gly Ser Lys385 390 395 400Leu Pro Glu Pro Ile Val Ser Thr Asp Ser Arg Leu Trp Val Glu Phe405 410 415Arg Ser Ser Ser Asn Trp Val Gly Lys Gly Phe Phe Ala Val Tyr Glu420 425 430Ala Ile Cys Gly Gly Asp Val Lys Lys Asp Tyr Gly His Ile Gln Ser435 440 445Pro Asn Tyr Pro Asp Asp Tyr Arg Pro Ser Lys Val Cys Ile Trp Arg450 455 460Ile Gln Val Ser Glu Gly Phe His Val Gly Leu Thr Phe Gln Ser Phe465 470 475 480
Glu Ile Glu Arg His Asp Ser Cys Ala Tyr Asp Tyr Leu Glu Val Arg485 490 495Asp Gly His Ser Glu Ser Ser Thr Leu Ile Gly Arg Tyr Cys Gly Tyr500 505 510Glu Lys Pro Asp Asp Ile Lys Ser Thr Ser Ser Arg Leu Trp Leu Lys515 520 525Phe Val Ser Asp Gly Ser Ile Asn Lys Ala Gly Phe Ala Val Asn Phe530 535 540Phe Lys Glu Val Asp Glu Cys Ser Arg Pro Asn Arg Gly Gly Cys Glu545 550 555 560Gln Arg Cys Leu Asn Thr Leu Gly Ser Tyr Lys Cys Ser Cys Asp Pro565 570 575Gly Tyr Glu Leu Ala Pro Asp Lys Arg Arg Cys Glu Ala Ala Cys Gly580 585 590Gly Phe Leu Thr Lys Leu Asn Gly Ser Ile Thr Ser Pro Gly Trp Pro595 600 605Lys Glu Tyr Pro Pro Asn Lys Asn Cys Ile Trp Gln Leu Val Ala Pro610 615 620Thr Gln Tyr Arg Ile Ser Leu Gln Phe Asp Phe Phe Glu Thr Glu Gly625 630 635 640Asn Asp Val Cys Lys Tyr Asp Phe Val Glu Val Arg Ser Gly Leu Thr645 650 655Ala Asp Ser Lys Leu His Gly Lys Phe Cys Gly Ser Glu Lys Pro Glu660 665 670Val Ile Thr Ser Gln Tyr Asn Asn Met Arg Val Glu Phe Lys Ser Asp675 680 685Asn Thr Val Ser Lys Lys Gly Phe Lys Ala His Phe Phe Ser Glu Lys690 695 700Arg Pro Ala Leu Gln Pro Pro Arg Gly Arg Pro His Gln Leu Lys Phe705 710 715 720Arg Val Gln Lys Arg Asn Arg Thr Pro Gln725 730<210>3<211>1821
<212>DNA<213>智人(Homo sapiens)<400>3tcccgaccag agcgtgtgtg gcccgatggg gtcatcccct ttgtcattgg gggaaacttc 60actggtagcc agagggcagt cttccggcag gccatgaggc actgggagaa gcacacctgt120gtcaccttcc tggagcgcac tgacgaggac agctatattg tgttcaccta tcgaccttgc180gggtgctgct cctacgtggg tcgccgcggc gggggccccc aggccatctc catcggcaag240aactgtgaca agttcggcat tgtggtccac gagctgggcc acgtcgtcgg cttctggcac300gaacacactc ggccagaccg ggaccgccac gtttccatcg ttcgtgagaa catccagcca360gggcaggagt ataacttcct gaagatggag cctcaggagg tggagtccct gggggagacc420tatgacttcg acagcatcat gcattacgct cggaacacat tctccagggg catcttcctg480gataccattg tccccaagta tgaggtgaac ggggtgaaac ctcccattgg ccaaaggaca540cggctcagca agggggacat tgcccaagcc cgcaagcttt acaagtgccc agcctgtgga600gagaccctgc aagacagcac aggcaacttc tcctcccctg aataccccaa tggctactct660gctcacatgc actgcgtgtg gcgcatctct gtcacacccg gggagaagat catcctgaac720ttcacgtccc tggacctgta ccgcagccgc ctgtgctggt acgactatgt ggaggtccga780gatggcttct ggaggaaggc gcccctccga ggccgcttct gcgggtccaa actccctgag840cctatcgtct ccactgacag ccgcctctgg gttgaattcc gcagcagcag caattgggtt900ggaaagggct tctttgcagt ctacgaagcc atctgcgggg gtgatgtgaa aaaggactat960ggccacattc aatcgcccaa ctacccagac gattaccggc ccagcaaagt ctgcatctgg 1020cggatccagg tgtctgaggg cttccacgtg ggcctcacat tccagtcctt tgagattgag 1080cgccacgaca gctgtgccta cgactatctg gaggtgcgcg acgggcacag tgagagcagc 1140accctcatcg ggcgctactg tggctatgag aagcctgatg acatcaagag cacgtccagc 1200cgcctctggc tcaagttcgt ctctgacggg tccattaaca aagcgggctt tgccgtcaac 1260tttttcaaag aggtggacga gtgctctcgg cccaaccgcg ggggctgtga gcagcggtgc 1320ctcaacaccc tgggcagcta caagtgcagc tgtgaccccg ggtacgagct ggccccagac 1380aagcgccgct gtgaggctgc ttgtggcgga ttcctcacca agctcaacgg ctccatcacc 1440agcccgggct ggcccaagga gtaccccccc aacaagaact gcatctggca gctggtggcc 1500cccacccagt accgcatctc cctgcagttt gacttctttg agacagaggg caatgatgtg 1560tgcaagtacg acttcgtgga ggtgcgcagt ggactcacag ctgactccaa gctgcatggc 1620aagttctgtg gttctgagaa gcccgaggtc atcacctccc agtacaacaa catgcgcgtg 1680gagttcaagt ccgacaacac cgtgtccaaa aagggcttca aggcccactt cttctcagaa 1740aagaggccag ctctgcagcc ccctcgggga cgcccccacc agctcaaatt ccgagtgcag 1800aaaagaaacc ggacccccca g 1821<210>4<21l>610<212>PRT<213>智人(Homo sapiens)<400>4Ala Ala Thr Ser Arg Pro Glu Arg Val Trp Pro Asp Gly Val Ile Pro1 5 10 15Phe Val Ile Gly Gly Asn Phe Thr Gly Ser Gln Arg Ala Val Phe Arg20 25 30Gln Ala Met Arg His Trp Glu Lys His Thr Cys Val Thr Phe Leu Glu35 40 45
Arg Thr Asp Glu Asp Ser Tyr Ile Val Phe Thr Tyr Arg Pro Cys Gly50 55 60Cys Cys Ser Tyr Val Gly Arg Arg Gly Gly Gly Pro Gln Ala Ile Ser65 70 75 80Ile Gly Lys Asn Cys Asp Lys Phe Gly Ile Val Val His Glu Leu Gly85 90 95His Val Val Gly Phe Trp His Glu His Thr Arg Pro Asp Arg Asp Arg100 105 110His Val Ser Ile Val Arg Glu Asn Ile Gln Pro Gly Gln Glu Tyr Asn115 120 125Phe Leu Lys Met Glu Pro Gln Glu Val Glu Ser Leu Gly Glu Thr Tyr130 135 140Asp Phe Asp Ser Ile Met His Tyr Ala Arg Asn Thr Phe Ser Arg Gly145 150 155 160Ile Phe Leu Asp Thr Ile Val Pro Lys Tyr Glu Val Asn Gly Val Lys165 170 175Pro Pro Ile Gly Gln Arg Thr Arg Leu Ser Lys Gly Asp Ile Ala Gln180 185 190Ala Arg Lys Leu Tyr Lys Cys Pro Ala Cys Gly Glu Thr Leu Gln Asp195 200 205Ser Thr Gly Asn Phe Ser Ser Pro Glu Tyr Pro Asn Gly Tyr Ser Ala210 215 220His Met His Cys Val Trp Arg Ile Ser Val Thr Pro Gly Glu Lys Ile225 230 235 240Ile Leu Asn Phe Thr Ser Leu Asp Leu Tyr Arg Ser Arg Leu Cys Trp245 250 255Tyr Asp Tyr Val Glu Val Arg Asp Gly Phe Trp Arg Lys Ala Pro Leu260 265 270Arg Gly Arg Phe Cys Gly Ser Lys Leu Pro Glu Pro Ile Val Ser Thr275 280 285Asp Ser Arg Leu Trp Val Glu Phe Arg Ser Ser Ser Asn Trp Val Gly290 295 300Lys Gly Phe Phe Ala Val Tyr Glu Ala Ile Cys Gly Gly Asp Val Lys305 310 315 320Lys Asp Tyr Gly His Ile Gln Ser Pro Asn Tyr Pro Asp Asp Tyr Arg
325 330 335Pro Ser Lys Val Cys Ile Trp Arg Ile Gln Val Ser Glu Gly Phe His340 345 350Val Gly Leu Thr Phe Gln Ser Phe Glu Ile Glu Arg His Asp Ser Cys355 360 365Ala Tyr Asp Tyr Leu Glu Val Arg Asp Gly His Ser Glu Ser Ser Thr370 375 380Leu Ile Gly Arg Tyr Cys Gly Tyr Glu Lys Pro Asp Asp Ile Lys Ser385 390 395 400Thr Ser Ser Arg Leu Trp Leu Lys Phe Val Ser Asp Gly Ser Ile Asn405 410 415Lys Ala Gly Phe Ala Val Asn Phe Phe Lys Glu Val Asp Glu Cys Ser420 425 430Arg Pro Asn Arg Gly Gly Cys Glu Gln Arg Cys Leu Asn Thr Leu Gly435 440 445Ser Tyr Lys Cys Ser Cys Asp Pro Gly Tyr Glu Leu Ala Pro Asp Lys450 455 460Arg Arg Cys Glu Ala Ala Cys Gly Gly Phe Leu Thr Lys Leu Asn Gly465 470 475 480Ser Ile Thr Ser Pro Gly Trp Pro Lys Glu Tyr Pro Pro Asn Lys Asn485 490 495Cys Ile Trp Gln Leu Val Ala Pro Thr Gln Tyr Arg Ile Ser Leu Gln500 505 510Phe Asp Phe Phe Glu Thr Glu Gly Asn Asp Val Cys Lys Tyr Asp Phe515 520 525Val Glu Val Arg Ser Gly Leu Thr Ala Asp Ser Lys Leu His Gly Lys530 535 540Phe Cys Gly Ser Glu Lys Pro Glu Val Ile Thr Ser Gln Tyr Asn Asn545 550 555 560Met Arg Val Glu Phe Lys Ser Asp Asn Thr Val Ser Lys Lys Gly Phe565 570 575Lys Ala His Phe Phe Ser Glu Lys Arg Pro Ala Leu Gln Pro Pro Arg580 585 590Gly Arg Pro His Gln Leu Lys Phe Arg Val Gln Lys Arg Asn Arg Thr595 600 605
Pro Gln610<210>5<211>1547<212>DNA<213>智人(Homo sapiens)<400>5ggggacttct tgaacttgca gggagaataa cttgcgcacc ccactttgcg ccggtgcctt 60tgccccagcg gagcctgctt cgccatctcc gagccccacc gcccctccac tcctcggcct120tgcccgacac tgagacgctg ttcccagcgt gaaaagagag actgcgcggc cggcacccgg180gagaaggagg aggcaaagaa aaggaacgga cattcggtcc ttgcgccagg tcctttgacc240agagtttttc catgtggacg ctctttcaat ggacgtgtcc ccgcgtgctt cttagacgga300ctgcggtctc ctaaaggtcg accatggtgg ccgggacccg ctgtcttcta gcgttgctgc360ttccccaggt cctcctgggc ggcgcggctg gcctcgttcc ggagctgggc cgcaggaagt420tcgcggcggc gtcgtcgggc cgcccctcat cccagccctc tgacgaggtc ctgagcgagt480tcgagttgcg gctgctcagc atgttcggcc tgaaacagag acccaccccc agcagggacg540ccgtggtgcc cccctacatg ctagacctgt atcgcaggca ctcaggtcag ccgggctcac600ccgccccaga ccaccggttg gagagggcag ccagccgagc caacactgtg cgcagcttcc660accatgaaga atctttggaa gaactaccag aaacgagtgg gaaaacaacc cggagattct720tctttaattt aagttctatc cccacggagg agtttatcac ctcagcagag cttcaggttt780tccgagaaca gatgcaagat gctttaggaa acaatagcag tttccatcac cgaattaata840tttatgaaat cataaaacct gcaacagcca actcgaaatt ccccgtgacc agacttttgg900acaccaggtt ggtgaatcag aatgcaagca ggtgggaaag ttttgatgtc acccccgctg960tgatgcggtg gactgcacag ggacacgcca accatggatt cgtggtggaa gtggcccact 1020tggaggagaa acaaggtgtc tccaagagac atgttaggat aagcaggtct ttgcaccaag 1080atgaacacag ctggtcacag ataaggccat tgctagtaac ttttggccat gatggaaaag 1140ggcatcctct ccacaaaaga gaaaaacgtc aagccaaaca caaacagcgg aaacgcctta 1200agtccagctg taagagacac cctttgtacg tggacttcag tgacgtgggg tggaatgact 1260ggattgtggc tcccccgggg tatcacgcct tttactgcca cggagaatgc ccttttcctc 1320tggctgatca tctgaactcc actaatcatg ccattgttca gacgttggtc aactctgtta 1380actctaagat tcctaaggca tgctgtgtcc cgacagaact cagtgctatc tcgatgctgt 1440accttgacga gaatgaaaag gttgtattaa agaactatca ggacatggtt gtggagggtt 1500gtgggtgtcg ctagtacagc aaaattaaat acataaatat atatata 1547<210>6<211>396<212>PRT<213>智人(Homo sapiens)<400>6Met Val Ala Gly Thr Arg Cys Leu Leu Ala Leu Leu Leu Pro Gln Val1 5 10 15Leu Leu Gly Gly Ala Ala Gly Leu Val Pro Glu Leu Gly Arg Arg Lys20 25 30Phe Ala Ala Ala Ser Ser Gly Arg Pro Ser Ser Gln Pro Ser Asp Glu35 40 45
Val Leu Ser Glu Phe Glu Leu Arg Leu Leu Ser Met Phe Gly Leu Lys50 55 60Gln Arg Pro Thr Pro Ser Arg Asp Ala Val Val Pro Pro Tyr Met Leu65 70 75 80Asp Leu Tyr Arg Arg His Ser Gly Gln Pro Gly Ser Pro Ala Pro Asp85 90 95His Arg Leu Glu Arg Ala Ala Ser Arg Ala Asn Thr Val Arg Ser Phe100 105 110His His Glu Glu Ser Leu Glu Glu Leu Pro Glu Thr Ser Gly Lys Thr115 120 125Thr Arg Arg Phe Phe Phe Asn Leu Ser Ser Ile Pro Thr Glu Glu Phe130 135 140Ile Thr Ser Ala Glu Leu Gln Val Phe Arg Glu Gln Met Gln Asp Ala145 150 155 160Leu Gly Asn Asn Ser Ser Phe His His Arg Ile Asn Ile Tyr Glu Ile165 170 175Ile Lys Pro Ala Thr Ala Asn Ser Lys Phe Pro Val Thr Arg Leu Leu180 185 190Asp Thr Arg Leu Val Asn Gln Asn Ala Ser Arg Trp Glu Ser Phe Asp195 200 205Val Thr Pro Ala Val Met Arg Trp Thr Ala Gln Gly His Ala Asn His210 215 220Gly Phe Val Val Glu Val Ala His Leu Glu Glu Lys Gln Gly Val Ser225 230 235 240Lys Arg His Val Arg Ile Ser Arg Ser Leu His Gln Asp Glu His Ser245 250 255Trp Ser Gln Ile Arg Pro Leu Leu Val Thr Phe Gly His Asp Gly Lys260 265 270Gly His Pro Leu His Lys Arg Glu Lys Arg Gln Ala Lys His Lys Gln275 280 285Arg Lys Arg Leu Lys Ser Ser Cys Lys Arg His Pro Leu Tyr Val Asp290 295 300Phe Ser Asp Val Gly Trp Asn Asp Trp Ile Val Ala Pro Pro Gly Tyr305 310 315 320
His Ala Phe Tyr Cys His Gly Glu Cys Pro Phe Pro Leu Ala Asp His325 330 335Leu Asn Ser Thr Asn His Ala Ile Val Gln Thr Leu Val Asn Ser Val340 345 350Asn Ser Lys Ile Pro Lys Ala Cys Cys Val Pro Thr Glu Leu Ser Ala355 360 365Ile Ser Met Leu Tyr Leu Asp Glu Asn Glu Lys Val Val Leu Lys Asn370 375 380Tyr Gln Asp Met Val Val Glu Gly Cys Gly Cys Arg385 390 395<210>7<211>1794<212>DNA<213>智人(Homo sapiens)<400>7agatcttgaa aacacccggg ccacacacgc cgcgacccac agctctttct cagcgttgga 60gtggagacgg cgcccgcagc gccctgcgcg ggtgaggtcc gcgcagctgc tggggaagag120cccacctgtc aggctgcgct gggtcagcgc agcaagtggg gctggccgct atctcgctgc180acccggccgc gtcccgggct ccgtgcgccc tcgccccagc tggtttggag ttcaaccctc240ggctccgccg ccggctcctt gcgccttcgg agtgtcccgc agcgacgccg ggagccgacg300cgccgcgcgg gtacctagcc atggctgggg cgagcaggct gctgtttctg tggctgggct360gcttctgcgt gagcctggcg cagggagaga gaccgaagcc acctttcccg gagctccgca420aagctgtgcc aggtgaccgc acggcaggtg ctggcccgga ctccgagctg gagccgcaag480acaaggtctc tgaacacatg ctgcggctct atgacaggta cagcacggtc caggcggccc540ggacaccggg ctccctggag ggaggctcgg agccctggcg ccctcggctc ctgcgcgaag600gcaacacggt tcgcagcttt cgggcggcag cagcagaaac tcttgaaaga aaaggactgt660atatcttcaa tctgacatcg ctaaccaagt ctgaaaacat tttgtctgcc acactgtatt720tctgtattgg agagctagga aacatcagcc tgagttgtcc agtgtctgga ggatgctccc780atcatgctca gaggaaacac attcagattg atctttctgc atggaccctc aaattcagca840gaaaccaaag tcaactcctt ggccatctgt cagtggatat ggccaaatct catcgagata900ttatgtcctg gctgtctaaa gatatcactc aattcttgag gaaggccaaa gaaaaagaag960agttcctcat aggatttaac attacgtcca agggacgcca gctgccaaag aggaggttac 1020cttttccaga gccttatatc ttggtatatg ccaatgatgc cgccatttct gagccagaaa 1080gtgtggtatc aagcttacag ggacaccgga attttcccac tggaactgtt cccaaatggg 1140atagccacat cagagctgcc ctttccattg agcggaggaa gaagcgctct actgggctct 1200tgctgcctct gcagaacaac gagcttcctg gggcagaata ccagtataaa aaggatgagg 1260tgtgggagga gagaaagcct tacaagaccc ttcaggctca ggcccctgaa aagagtaaga 1320ataaaaagaa acagagaaag gggcctcatc ggaagagcca gaggctccaa tttgatgagc 1380agaccctgaa aaaggcaagg agaaagcagt ggattgaacc tcggaattgc gccaggagat 1440acctcaaggt agactttgca gatattggct ggagtgaatg gattatctcc cccaagtcct 1500ttgatgccta ttattgctct ggagcatgcc agttccccat gccaaagtct ttgaagccat 1560caaatcatgc taccatccag agtatagtga gagctgtggg ggtcgttcct gggattcctg 1620agccttgctg tgtaccagaa aagatgtcct cactcagtat tttattcttt gatgaaaata 1680agaatgtagt gcttaaagta taccctaaca tgacagtaga gtcttgcgct tgcagataac 1740ctggcaaaga actcatttga atgcttaatt caatctctag agtcgacgga attc 1794
<210>8<211>472<212>PRT<213>智人(Homo sapiens)<400>8Met Ala Gly Ala Ser Arg Leu Leu Phe Leu Trp Leu Gly Cys Phe Cys1 5 10 15Val Ser Leu Ala Gln Gly Glu Arg Pro Lys Pro Pro Phe Pro Glu Leu20 25 30Arg Lys Ala Val Pro Gly Asp Arg Thr Ala Gly Ala Gly Pro Asp Ser35 40 45Glu Leu Glu Pro Gln Asp Lys Val Ser Glu His Met Leu Arg Leu Tyr50 55 60Asp Arg Tyr Ser Thr Val Gln Ala Ala Arg Thr Pro Gly Ser Leu Glu65 70 75 80Gly Gly Ser Glu Pro Trp Arg Pro Arg Leu Leu Arg Glu Gly Asn Thr85 90 95Val Arg Ser Phe Arg Ala Ala Ala Ala Glu Thr Leu Glu Arg Lys Gly100 105 110Leu Tyr Ile Phe Asn Leu Thr Ser Leu Thr Lys Ser Glu Asn Ile Leu115 120 125Ser Ala Thr Leu Tyr Phe Cys Ile Gly Glu Leu Gly Asn Ile Ser Leu130 135 140Ser Cys Pro Val Ser Gly Gly Cys Ser His His Ala Gln Arg Lys His145 150 155 160Ile Gln Ile Asp Leu Ser Ala Trp Thr Leu Lys Phe Ser Arg Asn Gln165 170 175Ser Gln Leu Leu Gly His Leu Ser Val Asp Met Ala Lys Ser His Arg180 185 190Asp Ile Met Ser Trp Leu Ser Lys Asp Ile Thr Gln Phe Leu Arg Lys195 200 205Ala Lys Glu Lys Glu Glu Phe Leu Ile Gly Phe Asn Ile Thr Ser Lys210 215 220Gly Arg Gln Leu Pro Lys Arg Arg Leu Pro Phe Pro Glu Pro Tyr Ile225 230 235 240Leu Val Tyr Ala Asn Asp Ala Ala Ile Ser Glu Pro Glu Ser Val Val
245 250 255Ser Ser Leu Gln Gly His Arg Asn Phe Pro Thr Gly Thr Val Pro Lys260 265 270Trp Asp Ser His Ile Arg Ala Ala Leu Ser Ile Glu Arg Arg Lys Lys275 280 285Arg Ser Thr Gly Leu Leu Leu Pro Leu Gln Asn Asn Glu Leu Pro Gly290 295 300Ala Glu Tyr Gln Tyr Lys Lys Asp Glu Val Trp Glu Glu Arg Lys Pro305 310 315 320Tyr Lys Thr Leu Gln Ala Gln Ala Pro Glu Lys Ser Lys Asn Lys Lys325 330 335Lys Gln Arg Lys Gly Pro His Arg Lys Ser Gln Arg Leu Gln Phe Asp340 345 350Glu Gln Thr Leu Lys Lys Ala Arg Arg Lys Gln Trp Ile Glu Pro Arg355 360 365Asn Cys Ala Arg Arg Tyr Leu Lys Val Asp Phe Ala Asp Ile Gly Trp370 375 380Ser Glu Trp Ile Ile Ser Pro Lys Ser Phe Asp Ala Tyr Tyr Cys Ser385 390 395 400Gly Ala Cys Gln Phe Pro Met Pro Lys Ser Leu Lys Pro Ser Asn His405 410 415Ala Thr Ile Gln Ser Ile Val Arg Ala Val Gly Val Val Pro Gly Ile420 425 430Pro Glu Pro Cys Cys Val Pro Glu Lys Met Ser Ser Leu Ser Ile Leu435 440 445Phe Phe Asp Glu Asn Lys Asn Val Val Leu Lys Val Tyr Pro Asn Met450 455 460Thr Val Glu Ser Cys Ala Cys Arg465 470<210>9<211>1999<212>DNA<213>智人(Homo sapiens)<400>9gagggagggg ccgccgggga agaggaggag gaaggaaaga aagaaagcga gggagggaaa 60gaggaggaag gaagatgcga gaaggcagag gaggagggag ggagggaagg agcgcggagc120
ccggcccgga agctaggtga gtgtggcatc cgagctgagg gacgcgagcc tgagacgccg 180ctgctgctcc ggctgagtat ctagcttgtc tccccgatgg gattcccgtc caagctatct 240cgagcctgca gcgccacagt ccccggccct cgcccaggtt cactgcaacc gttcagaggt 300ccccaggagc tgctgctggc gagcccgcta ctgcagggac ctatggagcc attccgtagt 360gccatcccga gcaacgcact gctgcagctt ccctgagcct ttccagcaag tttgttcaag 420attggctgtc aagaatcatg gactgttatt atatgccttg ttttctgtca agacaccatg 480attcctggta accgaatgct gatggtcgtt ttattatgcc aagtcctgct aggaggcgcg 540agccatgcta gtttgatacc tgagacgggg aagaaaaaag tcgccgagat tcagggccac 600gcgggaggac gccgctcagg gcagagccat gagctcctgc gggacttcga ggcgacactt 660ctgcagatgt ttgggctgcg ccgccgcccg cagcctagca agagtgccgt cattccggac 720tacatgcggg atctttaccg gcttcagtct ggggaggagg aggaagagca gatccacagc 780actggtcttg agtatcctga gcgcccggcc agccgggcca acaccgtgag gagcttccac 840cacgaagaac atctggagaa catcccaggg accagtgaaa actctgcttt tcgtttcctc 900tttaacctca gcagcatccc tgagaacgag gcgatctcct ctgcagagct tcggctcttc 960cgggagcagg tggaccaggg ccctgattgg gaaaggggct tccaccgtat aaacatttat 1020gaggttatga agcccccagc agaagtggtg cctgggcacc tcatcacacg actactggac 1080acgagactgg tccaccacaa tgtgacacgg tgggaaactt ttgatgtgag ccctgcggtc 1140cttcgctgga cccgggagaa gcagccaaac tatgggctag ccattgaggt gactcacctc 1200catcagactc ggacccacca gggccagcat gtcaggatta gccgatcgtt acctcaaggg 1260agtgggaatt gggcccagct ccggcccctc ctggtcacct ttggccatga tggccggggc 1320catgccttga cccgacgccg gagggccaag cgtagcccta agcatcactc acagcgggcc 1380aggaagaaga ataagaactg ccggcgccac tcgctctatg tggacttcag cgatgtgggc 1440tggaatgact ggattgtggc cccaccaggc taccaggcct tctactgcca tggggactgc 1500ccctttccac tggctgacca cctcaactca accaaccatg ccattgtgca gaccctggtc 1560aattctgtca attccagtat ccccaaagcc tgttgtgtgc ccactgaact gagtgccatc 1620tccatgctgt acctggatga gtatgataag gtggtactga aaaattatca ggagatggta 1680gtagagggat gtgggtgccg ctgagatcag gcagtccttg aggatagaca gatatacaca 1740ccacacacac acaccacata caccacacac acacgttccc atccactcac ccacacacta 1800cacagactgc ttccttatag ctggactttt atttaaaaaa aaaaaaaaaa aaatggaaaa 1860aatccctaaa cattcacctt gaccttattt atgactttac gtgcaaatgt tttgaccata 1920ttgatcatat attttgacaa aatatattta taactacgta ttaaaagaaa aaaataaaat 1980gagtcattat tttaaaggt 1999<210>10<211>408<212>PRT<213>智人(Homo sapiens)<400>10Met Ile Pro Gly Asn Arg Met Leu Met Val Val Leu Leu Cys Gln Val1 5 10 15Leu Leu Gly Gly Ala Ser His Ala Ser Leu Ile Pro Glu Thr Gly Lys20 25 30Lys Lys Val Ala Glu Ile Gln Gly His Ala Gly Gly Arg Arg Ser Gly35 40 45Gln Ser His Glu Leu Leu Arg Asp Phe Glu Ala Thr Leu Leu Gln Met50 55 60Phe Gly Leu Arg Arg Arg Pro Gln Pro Ser Lys Ser Ala Val Ile Pro
65 70 75 80Asp Tyr Met Arg Asp Leu Tyr Arg Leu Gln Ser Gly Glu Glu Glu Glu85 90 95Glu Gln Ile His Ser Thr Gly Leu Glu Tyr Pro Glu Arg Pro Ala Ser100 105 110Arg Ala Asn Thr Val Arg Ser Phe His His Glu Glu His Leu Glu Asn115 120 125Ile Pro Gly Thr Ser Glu Asn Ser Ala Phe Arg Phe Leu Phe Asn Leu130 135 140Ser Ser Ile Pro Glu Asn Glu Ala Ile Ser Ser Ala Glu Leu Arg Leu145 150 155 160Phe Arg Glu Gln Val Asp Gln Gly Pro Asp Trp Glu Arg Gly Phe His165 170 175Arg Ile Asn Ile Tyr Glu Val Met Lys Pro Pro Ala Glu Val Val Pro180 185 190Gly His Leu Ile Thr Arg Leu Leu Asp Thr Arg Leu Val His His Asn195 200 205Val Thr Arg Trp Glu Thr Phe Asp Val Ser Pro Ala Val Leu Arg Trp210 215 220Thr Arg Glu Lys Gln Pro Asn Tyr Gly Leu Ala Ile Glu Val Thr His225 230 235 240Leu His Gln Thr Arg Thr His Gln Gly Gln His Val Arg Ile Ser Arg245 250 255Ser Leu Pro Gln Gly Ser Gly Asn Trp Ala Gln Leu Arg Pro Leu Leu260 265 270Val Thr Phe Gly His Asp Gly Arg Gly His Ala Leu Thr Arg Arg Arg275 280 285Arg Ala Lys Arg Ser Pro Lys His His Ser Gln Arg Ala Arg Lys Lys290 295 300Asn Lys Asn Cys Arg Arg His Ser Leu Tyr Val Asp Phe Ser Asp Val305 310 315 320Gly Trp Asn Asp Trp Ile Val Ala Pro Pro Gly Tyr Gln Ala Phe Tyr325 330 335Cys His Gly Asp Cys Pro Phe Pro Leu Ala Asp His Leu Asn Ser Thr340 345 350
Asn His Ala Ile Val Gln Thr Leu Val Asn Ser Val Asn Ser Ser Ile355 360 365Pro Lys Ala Cys Cys Val Pro Thr Glu Leu Ser Ala Ile Ser Met Leu370 375 380Tyr Leu Asp Glu Tyr Asp Lys Val Val Leu Lys Asn Tyr Gln Glu Met385 390 395 400Val Val Glu Gly Cys Gly Cys Arg405<210>11<211>2207<212>DNA<213>智人(Homo sapiens)<400>11ctcttgaaga gggctggtat atttgtgcct gctggaggtg gaattaacag taagaaggag 60aaagggattg aatggactta caggaaggat ttcaagtaaa ttcagggaaa cacatttact120tgaatagtac aacctagagt attattttac actaagacga cacaaaagat gttaaagtta180tcaccaagct gccggacaga tatatattcc aacaccaagg tgcagatcag catagatctg240tgattcagaa atcaggattt gttttggaaa gagctcaagg gttgagaaga actcaaaagc300aagtgaagat tactttggga actacagttt atcagaagat caacttttgc taattcaaat360accaaaggcc tgattatcat aaattcatat aggaatgcat aggtcatctg atcaaataat420attagccgtc ttctgctaca tcaatgcagc aaaaactctt aacaactgtg gataattgga480aatctgagtt tcagctttct tagaaataac tactcttgac atattccaaa atatttaaaa540taggacagga aaatcggtga ggatgttgtg ctcagaaatg tcactgtcat gaaaaatagg600taaatttgtt ttttcagcta ctgggaaact gtacctccta gaaccttagg tttttttttt660ttttaagagg acaagaagga ctaaaaatat caacttttgc ttttggacaa aaatgcatct720gactgtattt ttacttaagg gtattgtggg tttcctctgg agctgctggg ttctagtggg780ttatgcaaaa ggaggtttgg gagacaatca tgttcactcc agttttattt atagaagact840acggaaccac gaaagacggg aaatacaaag ggaaattctc tctatcttgg gtttgcctca900cagacccaga ccattttcac ctggaaaaca agcgtcctct gcacctctct ttatgctgga960tctctacaat gccatgacca atgaagaaaa tcctgaagag tcggagtact cagtaagggc 1020atccttggca gaagagacca gaggggcaag aaagggatac ccagcctctc ccaatgggta 1080tcctcgtcgc atacagttat ctcggacgac tcctctgacc acccagagtc ctcctctagc 1140cagcctccat gataccaact ttctgaatga tgctgacatg gtcatgagct ttgtcaactt 1200agttgaaaga gacaaggatt tttctcacca gcgaaggcat tacaaagaat ttcgatttga 1260tcttacccaa attcctcatg gagaggcagt gacagcagct gaattccgga tatacaagga 1320ccggagcaac aaccgatttg aaaatgaaac aattaagatt agcatatatc aaatcatcaa 1380ggaatacaca aatagggatg cagatctgtt cttgttagac acaagaaagg cccaagcttt 1440agatgtgggt tggcttgtct ttgatatcac tgtgaccagc aatcattggg tgattaatcc 1500ccagaataat ttgggcttac agctctgtgc agaaacaggg gatggacgca gtatcaacgt 1560aaaatctgct ggtcttgtgg gaagacaggg acctcagtca aaacaaccat tcatggtggc 1620cttcttcaag gcgagtgagg tacttcttcg atccgtgaga gcagccaaca aacgaaaaaa 1680tcaaaaccgc aataaatcca gctctcatca ggactcctcc agaatgtcca gtgttggaga 1740ttataacaca agtgagcaaa aacaagcctg taagaagcac gaactctatg tgagcttccg 1800ggatctggga tggcaggact ggattatagc accagaagga tacgctgcat tttattgtga 1860tggagaatgt tcttttccac ttaacgccca tatgaatgcc accaaccacg ctatagttca 1920gactctggtt catctgatgt ttcctgacca cgtaccaaag ccttgttgtg ctccaaccaa 1980
attaaatgcc atctctgttc tgtactttga tgacagctcc aatgtcattt tgaaaaaata 2040tagaaatatg gtagtacgct catgtggctg ccactaatat taaataatat tgataataac 2100aaaaagatct gtattaaggt ttatggctgc aataaaaagc atactttcag acaaacgggg 2160aatttcctaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaa2207<210>12<211>454<212>PRT<213>智人(Homo sapiens)<400>12Met His Leu Thr Val Phe Leu Leu Lys Gly Ile Val Gly Phe Leu Trp1 5 10 15Ser Cys Trp Val Leu Val Gly Tyr Ala Lys Gly Gly Leu Gly Asp Asn20 25 30His Val His Ser Ser Phe Ile Tyr Arg Arg Leu Arg Asn His Glu Arg35 40 45Arg Glu Ile Gln Arg Glu Ile Leu Ser Ile Leu Gly Leu Pro His Arg50 55 60Pro Arg Pro Phe Ser Pro Gly Lys Gln Ala Ser Ser Ala Pro Leu Phe65 70 75 80Met Leu Asp Leu Tyr Asn Ala Met Thr Asn Glu Glu Asn Pro Glu Glu85 90 95Ser Glu Tyr Ser Val Arg Ala Ser Leu Ala Glu Glu Thr Arg Gly Ala100 105 110Arg Lys Gly Tyr Pro Ala Ser Pro Asn Gly Tyr Pro Arg Arg Ile Gln115 120 125Leu Ser Arg Thr Thr Pro Leu Thr Thr Gln Ser Pro Pro Leu Ala Ser130 135 140Leu His Asp Thr Asn Phe Leu Asn Asp Ala Asp Met Val Met Ser Phe145 150 155 160Val Asn Leu Val Glu Arg Asp Lys Asp Phe Ser His Gln Arg Arg His165 170 175Tyr Lys Glu Phe Arg Phe Asp Leu Thr Gln Ile Pro His Gly Glu Ala180 185 190Val Thr Ala Ala Glu Phe Arg Ile Tyr Lys Asp Arg Ser Asn Asn Arg195 200 205Phe Glu Asn Glu Thr Ile Lys Ile Ser Ile Tyr Gln Ile Ile Lys Glu210 215 220
Tyr Thr Asn Arg Asp Ala Asp Leu Phe Leu Leu Asp Thr Arg Lys Ala225 230 235 240Gln Ala Leu Asp Val Gly Trp Leu Val Phe Asp Ile Thr Val Thr Ser245 250 255Asn His Trp Val Ile Asn Pro Gln Asn Asn Leu Gly Leu Gln Leu Cys260 265 270Ala Glu Thr Gly Asp Gly Arg Ser Ile Asn Val Lys Ser Ala Gly Leu275 280 285Val Gly Arg Gln Gly Pro Gln Ser Lys Gln Pro Phe Met Val Ala Phe290 295 300Phe Lys Ala Ser Glu Val Leu Leu Arg Ser Val Arg Ala Ala Asn Lys305 310 315 320Arg Lys Asn Gln Asn Arg Asn Lys Ser Ser Ser His Gln Asp Ser Ser325 330 335Arg Met Ser Ser Val Gly Asp Tyr Asn Thr Ser Glu Gln Lys Gln Ala340 345 350Cys Lys Lys His Glu Leu Tyr Val Ser Phe Arg Asp Leu Gly Trp Gln355 360 365Asp Trp Ile Ile Ala Pro Glu Gly Tyr Ala Ala Phe Tyr Cys Asp Gly370 375 380Glu Cys Ser Phe Pro Leu Asn Ala His Met Asn Ala Thr Asn His Ala385 390 395 400Ile Val Gln Thr Leu Val His Leu Met Phe Pro Asp His Val Pro Lys405 410 415Pro Cys Cys Ala Pro Thr Lys Leu Asn Ala Ile Ser Val Leu Tyr Phe420 425 430Asp Asp Ser Ser Asn Val Ile Leu Lys Lys Tyr Arg Asn Met Val Val435 440 445Arg Ser Cys Gly Cys His450<210>13<211>396<212>DNA<213>智人(Homo sapiens)<400>13
aatcaaaacc gcaataaatc cagctctcat caggactcct ccagaatgtc cagtgttgga60gattataaca caagtgagca aaaacaagcc tgtaagaagc acgaactcta tgtgagcttc 120cgggatctgg gatggcagga ctggattata gcaccagaag gatacgctgc attttattgt 180gatggagaat gttcttttcc acttaacgcc catatgaatg ccaccaacca cgctatagtt 240cagactctgg ttcatctgat gtttcctgac cacgtaccaa agccttgttg tgctccaacc 300aaattaaatg ccatctctgt tctgtacttt gatgacagct ccaatgtcat tttgaaaaaa 360tatagaaata tggtagtacg ctcatgtggc tgccac 396<210>14<211>132<212>PRT<213>智人(Homo sapiens)<400>14Asn Gln Asn Arg Asn Lys Ser Ser Ser His Gln Asp Ser Ser Arg Met1 5 10 15Ser Set Val Gly Asp Tyr Asn Thr Ser Glu Gln Lys Gln Ala Cys Lys20 25 30Lys His Glu Leu Tyr Val Ser Phe Arg Asp Leu Gly Trp Gln Asp Trp35 40 45Ile Ile Ala Pro Glu Gly Tyr Ala Ala Phe Tyr Cys Asp Gly Glu Cys50 55 60Ser Phe Pro Leu Asn Ala His Met Asn Ala Thr Asn His Ala Ile Val65 70 75 80Gln Thr Leu Val His Leu Met Phe Pro Asp His Val Pro Lys Pro Cys85 90 95Cys Ala Pro Thr Lys Leu Asn Ala Ile Ser Val Leu Tyr Phe Asp Asp100 105 110Ser Ser Asn Val Ile Leu Lys Lys Tyr Arg Asn Met Val Val Arg Ser115 120 125Cys Gly Cys His130<210>15<211>2943<212>DNA<213>智人(Homo sapiens)<400>15gcaactgggg gcgccccgga cgaccatgag agataaggac tgagggccag gaaggggaag 60cgagcccgcc gagaggtggc ggggactgct cacgccaagg gccacagcgg ccgcgctccg120gcctcgctcc gccgctccac gcctcgcggg atccgcgggg gcagcccggc cgggcgggga180tgccggggct ggggcggagg gcgcagtggc tgtgctggtg gtgggggctg ctgtgcagct240gctgcgggcc cccgccgctg cggccgccct tgcccgctgc cgcggccgcc gccgccgggg300
ggcagctgct gggggacggc gggagccccg gccgcacgga gcagccgccg ccgtcgccgc360agtcctcctc gggcttcctg taccggcggc tcaagacgca ggagaagcgg gagatgcaga420aggagatctt gtcggtgctg gggctcccgc accggccccg gcccctgcac ggcctccaac480agccgcagcc cccggcgctc cggcagcagg aggagcagca gcagcagcag cagctgcctc540gcggagagcc ccctcccggg cgactgaagt ccgcgcccct cttcatgctg gatctgtaca600acgccctgtc cgccgacaac gacgaggacg gggcgtcgga gggggagagg cagcagtcct660ggccccacga agcagccagc tcgtcccagc gtcggcagcc gcccccgggc gccgcgcacc720cgctcaaccg caagagcctt ctggcccccg gatctggcag cggcggcgcg tccccactga780ccagcgcgca ggacagcgcc ttcctcaacg acgcggacat ggtcatgagc tttgtgaacc840tggtggagta cgacaaggag ttctcccctc gtcagcgaca ccacaaagag ttcaagttca900acttatccca gattcctgag ggtgaggtgg tgacggctgc agaattccgc atctacaagg960actgtgttat ggggagtttt aaaaaccaaa cttttcttat cagcatttat caagtcttac 1020aggagcatca gcacagagac tctgacctgt ttttgttgga cacccgtgta gtatgggcct 1080cagaagaagg ctggctggaa tttgacatca cggccactag caatctgtgg gttgtgactc 1140cacagcataa catggggctt cagctgagcg tggtgacaag ggatggagtc cacgtccacc 1200cccgagccgc aggcctggtg ggcagagacg gcccttacga taagcagccc ttcatggtgg 1260ctttcttcaa agtgagtgag gtccacgtgc gcaccaccag gtcagcctcc agccggcgcc 1320gacaacagag tcgtaatcgc tctacccagt cccaggacgt ggcgcgggtc tccagtgctt 1380cagattacaa cagcagtgaa ttgaaaacag cctgcaggaa gcatgagctg tatgtgagtt 1440tccaagacct gggatggcag gactggatca ttgcacccaa gggctatgct gccaattact 1500gtgatggaga atgctccttc ccactcaacg cacacatgaa tgcaaccaac cacgcgattg 1560tgcagacctt ggttcacctt atgaaccccg agtatgtccc caaaccgtgc tgtgcgccaa 1620ctaagctaaa tgccatctcg gttctttact ttgatgacaa ctccaatgtc attctgaaaa 1680aatacaggaa tatggttgta agagcttgtg gatgccacta actcgaaacc agatgctggg 1740gacacacatt ctgccttgga ttcctagatt acatctgcct taaaaaaaca cggaagcaca 1800gttggaggtg ggacgatgag actttgaaac tatctcatgc cagtgcctta ttacccagga 1860agattttaaa ggacctcatt aataatttgc tcacttggta aatgacgtga gtagttgttg 1920gtctgtagca agctgagttt ggatgtctgt agcataaggt ctggtaactg cagaaacata 1980accgtgaagc tcttcctacc ctcctccccc aaaaacccac caaaattagt tttagctgta 2040gatcaagcta tttggggtgt ttgttagtaa atagggaaaa taatctcaaa ggagttaaat 2100gtattcttgg ctaaaggatc agctggttca gtactgtcta tcaaaggtag attttacaga 2160gaacagaaat cggggaagtg gggggaacgc ctctgttcag ttcattccca gaagtccaca 2220ggacgcacag cccaggccac agccagggct ccacggggcg cccttgtctc agtcattgct 2280gttgtatgtt cgtgctggag ttttgttggt gtgaaaatac acttatttca gccaaaacat 2340accatttcta cacctcaatc ctccatttgc tgtactcttt gctagtacca aaagtagact 2400gattacactg aggtgaggct acaaggggtg tgtaaccgtg taacacgtga aggcagtgct 2460cacctcttct ttaccagaac ggttctttga ccagcacatt aacttctgga ctgccggctc 2520tagtaccttt tcagtaaagt ggttctctgc ctttttacta tacagcatac cacgccacag 2580ggttagaacc aacgaagaaa ataaaatgag ggtgcccagc ttataagaat ggtgttaggg 2640ggatgagcat gctgtttatg aacggaaatc atgatttccc tgtagaaagt gaggctcaga 2700ttaaatttta gaatattttc taaatgtctt tttcacaatc atgtgactgg gaaggcaatt 2760tcatactaaa ctgattaaat aatacattta taatctacaa ctgtttgcac ttacagcttt 2820ttttgtaaat ataaactata atttattgtc tattttatat ctgttttgct gtggcgttgg 2880ggggggggcc gggcttttgg gggggggggt ttgtttgggg ggtgtcgtgg tgtgggcggg 2940cgg 2943<210>16<211>513<212>PRT<213>智人(Homo sapiens)<400>16
Met Pro Gly Leu Gly Arg Arg Ala Gln Trp Leu Cys Trp Trp Trp Gly1 5 10 15Leu Leu Cys Ser Cys Cys Gly Pro Pro Pro Leu Arg Pro Pro Leu Pro20 25 30Ala Ala Ala Ala Ala Ala Ala Gly Gly Gln Leu Leu Gly Asp Gly Gly35 40 45Ser Pro Gly Arg Thr Glu Gln Pro Pro Pro Ser Pro Gln Ser Ser Ser50 55 60Gly Phe Leu Tyr Arg Arg Leu Lys Thr Gln Glu Lys Arg Glu Met Gln65 70 75 80Lys Glu Ile Leu Ser Val Leu Gly Leu Pro His Arg Pro Arg Pro Leu85 90 95His Gly Leu Gln Gln Pro Gln Pro Pro Ala Leu Arg Gln Gln Glu Glu100 105 110Gln Gln Gln Gln Gln Gln Leu Pro Arg Gly Glu Pro Pro Pro Gly Arg115 120 125Leu Lys Ser Ala Pro Leu Phe Met Leu Asp Leu Tyr Asn Ala Leu Ser130 135 140Ala Asp Asn Asp Glu Asp Gly Ala Ser Glu Gly Glu Arg Gln Gln Ser145 150 155 160Trp Pro His Glu Ala Ala Ser Ser Ser Gln Arg Arg Gln Pro Pro Pro165 170 175Gly Ala Ala His Pro Leu Asn Arg Lys Ser Leu Leu Ala Pro Gly Ser180 185 190Gly Ser Gly Gly Ala Ser Pro Leu Thr Ser Ala Gln Asp Ser Ala Phe195 200 205Leu Asn Asp Ala Asp Met Val Met Ser Phe Val Asn Leu Val Glu Tyr210 215 220Asp Lys Glu Phe Ser Pro Arg Gln Arg His His Lys Glu Phe Lys Phe225 230 235 240Asn Leu Ser Gln Ile Pro Glu Gly Glu Val Val Thr Ala Ala Glu Phe245 250 255Arg Ile Tyr Lys Asp Cys Val Met Gly Ser Phe Lys Asn Gln Thr Phe260 265 270Leu Ile Ser Ile Tyr Gln Val Leu Gln Glu His Gln His Arg Asp Ser
275 280 285Asp Leu Phe Leu Leu Asp Thr Arg Val Val Trp Ala Ser Glu Glu Gly290 295 300Trp Leu Glu Phe Asp Ile Thr Ala Thr Ser Asn Leu Trp Val Val Thr305 310 315 320Pro Gln His Asn Met Gly Leu Gln Leu Ser Val Val Thr Arg Asp Gly325 330 335Val His Val His Pro Arg Ala Ala Gly Leu Val Gly Arg Asp Gly Pro340 345 350Tyr Asp Lys Gln Pro Phe Met Val Ala Phe Phe Lys Val Ser Glu Val355 360 365His Val Arg Thr Thr Arg Ser Ala Ser Ser Arg Arg Arg Gln Gln Ser370 375 380Arg Asn Arg Ser Thr Gln Ser Gln Asp Val Ala Arg Val Ser Ser Ala385 390 395 400Ser Asp Tyr Asn Ser Ser Glu Leu Lys Thr Ala Cys Arg Lys His Glu405 410 415Leu Tyr Val Ser Phe Gln Asp Leu Gly Trp Gln Asp Trp Ile Ile Ala420 425 430Pro Lys Gly Tyr Ala Ala Asn Tyr Cys Asp Gly Glu Cys Ser Phe Pro435 440 445Leu Asn Ala His Met Asn Ala Thr Asn His Ala Ile Val Gln Thr Leu450 455 460Val His Leu Met Asn Pro Glu Tyr Val Pro Lys Pro Cys Cys Ala Pro465 470 475 480Thr Lys Leu Asn Ala Ile Ser Val Leu Tyr Phe Asp Asp Asn Ser Asn485 490 495Val Ile Leu Lys Lys Tyr Arg Asn Met Val Val Arg Ala Cys Gly Cys500 505 510His<210>17<211>420<212>DNA<213>智人(Homo sapiens)<400>17
aggtcagcct ccagccggcg ccgacaacag agtcgtaatc gctctaccca gtcccaggac60gtggcgcggg tctccagtgc ttcagattac aacagcagtg aattgaaaac agcctgcagg 120aagcatgagc tgtatgtgag tttccaagac ctgggatggc aggactggat cattgcaccc 180aagggctatg ctgccaatta ctgtgatgga gaatgctcct tcccactcaa cgcacacatg 240aatgcaacca accacgcgat tgtgcagacc ttggttcacc ttatgaaccc cgagtatgtc 300cccaaaccgt gctgtgcgcc aactaagcta aatgccatct cggttcttta ctttgatgac 360aactccaatg tcattctgaa aaaatacagg aatatggttg taagagcttg tggatgccac 420<210>18<211>140<212>PRT<213>智人(Homo sapiens)<400>18Arg Ser Ala Ser Ser Arg Arg Arg Gln Gln Ser Arg Asn Arg Ser Thr1 5 10 15Gln Ser Gln Asp Val Ala Arg Val Ser Ser Ala Ser Asp Tyr Asn Ser20 25 30Ser Glu Leu Lys Thr Ala Cys Arg Lys His Glu Leu Tyr Val Ser Phe35 40 45Gln Asp Leu Gly Trp Gln Asp Trp Ile Ile Ala Pro Lys Gly Tyr Ala50 55 60Ala Asn Tyr Cys Asp Gly Glu Cys Ser Phe Pro Leu Asn Ala His Met65 70 75 80Asn Ala Thr Asn His Ala Ile Val Gln Thr Leu Val His Leu Met Asn85 90 95Pro Glu Tyr Val Pro Lys Pro Cys Cys Ala Pro Thr Lys Leu Asn Ala100 105 110Ile Ser Val Leu Tyr Phe Asp Asp Asn Ser Asn Val Ile Leu Lys Lys115 120 125Tyr Arg Asn Met Val Val Arg Ala Cys Gly Cys His130 135 140<210>19<211>1878<212>DNA<213>智人(Homo sapiens)<400>19gggcgcagcg gggcccgtct gcagcaagtg accgacggcc gggacggccg cctgccccct60ctgccacctg gggcggtgcg ggcccggagc ccggagcccg ggtagcgcgt agagccggcg 120cgatgcacgt gcgctcactg cgagctgcgg cgccgcacag cttcgtggcg ctctgggcac 180ccctgttcct gctgcgctcc gccctggccg acttcagcct ggacaacgag gtgcactcga 240
gcttcatcca ccggcgcctc cgcagccagg agcggcggga gatgcagcgc gagatcctct 300ccattttggg cttgccccac cgcccgcgcc cgcacctcca gggcaagcac aactcggcac 360ccatgttcat gctggacctg tacaacgcca tggcggtgga ggagggcggc gggcccggcg 420gccagggctt ctcctacccc tacaaggccg tcttcagtac ccagggcccc cctctggcca 480gcctgcaaga tagccatttc ctcaccgacg ccgacatggt catgagcttc gtcaacctcg 540tggaacatga caaggaattc ttccacccac gctaccacca tcgagagttc cggtttgatc 600tttccaagat cccagaaggg gaagctgtca cggcagccga attccggatc tacaaggact 660acatccggga acgcttcgac aatgagacgt tccggatcag cgtttatcag gtgctccagg 720agcacttggg cagggaatcg gatctcttcc tgctcgacag ccgtaccctc tgggcctcgg 780aggagggctg gctggtgttt gacatcacag ccaccagcaa ccactgggtg gtcaatccgc 840ggcacaacct gggcctgcag ctctcggtgg agacgctgga tgggcagagc atcaacccca 900agttggcggg cctgattggg cggcacgggc cccagaacaa gcagcccttc atggtggctt 960tcttcaaggc cacggaggtc cacttccgca gcatccggtc cacggggagc aaacagcgca 1020gccagaaccg ctccaagacg cccaagaacc aggaagccct gcggatggcc aacgtggcag 1080agaacagcag cagcgaccag aggcaggcct gtaagaagca cgagctgtat gtcagcttcc 1140gagacctggg ctggcaggac tggatcatcg cgcctgaagg ctacgccgcc tactactgtg 1200agggggagtg tgccttccct ctgaactcct acatgaacgc caccaaccac gccatcgtgc 1260agacgctggt ccacttcatc aacccggaaa cggtgcccaa gccctgctgt gcgcccacgc 1320agctcaatgc catctccgtc ctctacttcg atgacagctc caacgtcatc ctgaagaaat 1380acagaaacat ggtggtccgg gcctgtggct gccactagct cctccgagaa ttcagaccct 1440ttggggccaa gtttttctgg atcctccatt gctcgccttg gccaggaacc agcagaccaa 1500ctgccttttg tgagaccttc ccctccctat ccccaacttt aaaggtgtga gagtattagg 1560aaacatgagc agcatatggc ttttgatcag tttttcagtg gcagcatcca atgaacaaga 1620tcctacaagc tgtgcaggca aaacctagca ggaaaaaaaa acaacgcata aagaaaaatg 1680gccgggccag gtcattggct gggaagtctc agccatgcac ggactcgttt ccagaggtaa 1740ttatgagcgc ctaccagcca ggccacccag ccgtgggagg aagggggcgt ggcaaggggt 1800gggcacattg gtgtctgtgc gaaaggaaaa ttgacccgga agttcctgta ataaatgtca 1860caataaaacg aatgaatg1878<210>20<211>431<212>PRT<213>智人(Homo sapiens)<400>20Met His Val Arg Ser Leu Arg Ala Ala Ala Pro His Ser Phe Val Ala1 5 10 15Leu Trp Ala Pro Leu Phe Leu Leu Arg Ser Ala Leu Ala Asp Phe Ser20 25 30Leu Asp Asn Glu Val His Ser Ser Phe Ile His Arg Arg Leu Arg Ser35 40 45Gln Glu Arg Arg Glu Met Gln Arg Glu Ile Leu Ser Ile Leu Gly Leu50 55 60Pro His Arg Pro Arg Pro His Leu Gln Gly Lys His Asn Ser Ala Pro65 70 75 80Met Phe Met Leu Asp Leu Tyr Asn Ala Met Ala Val Glu Glu Gly Gly85 90 95
Gly Pro Gly Gly Gln Gly Phe Ser Tyr Pro Tyr Lys Ala Val Phe Ser100 105 110Thr Gln Gly Pro Pro Leu Ala Ser Leu Gln Asp Ser His Phe Leu Thr115 120 125Asp Ala Asp Met Val Met Ser Phe Val Asn Leu Val Glu His Asp Lys130 135 140Glu Phe Phe His Pro Arg Tyr His His Arg Glu Phe Arg Phe Asp Leu145 150 155 160Ser Lys Ile Pro Glu Gly Glu Ala Val Thr Ala Ala Glu Phe Arg Ile165 170 175Tyr Lys Asp Tyr Ile Arg Glu Arg Phe Asp Asn Glu Thr Phe Arg Ile180 185 190Ser Val Tyr Gln Val Leu Gln Glu His Leu Gly Arg Glu Ser Asp Leu195 200 205Phe Leu Leu Asp Ser Arg Thr Leu Trp Ala Ser Glu Glu Gly Trp Leu210 215 220Val Phe Asp Ile Thr Ala Thr Ser Asn His Trp Val Val Asn Pro Arg225 230 235 240His Asn Leu Gly Leu Gln Leu Ser Val Glu Thr Leu Asp Gly Gln Ser245 250 255Ile Asn Pro Lys Leu Ala Gly Leu Ile Gly Arg His Gly Pro Gln Asn260 265 270Lys Gln Pro Phe Met Val Ala Phe Phe Lys Ala Thr Glu Val His Phe275 280 285Arg Ser Ile Arg Ser Thr Gly Ser Lys Gln Arg Ser Gln Asn Arg Ser290 295 300Lys Thr Pro Lys Asn Gln Glu Ala Leu Arg Met Ala Asn Val Ala Glu305 310 315 320Asn Ser Ser Ser Asp Gln Arg Gln Ala Cys Lys Lys His Glu Leu Tyr325 330 335Val Ser Phe Arg Asp Leu Gly Trp Gln Asp Trp Ile Ile Ala Pro Glu340 345 350Gly Tyr Ala Ala Tyr Tyr Cys Glu Gly Glu Cys Ala Phe Pro Leu Asn355 360 365
Ser Tyr Met Asn Ala Thr Asn His Ala Ile Val Gln Thr Leu Val His370 375 380Phe Ile Asn Pro Glu Thr Val Pro Lys Pro Cys Cys Ala Pro Thr Gln385 390 395 400Leu Asn Ala Ile Ser Val Leu Tyr Phe Asp Asp Ser Ser Asn Val Ile405 410 415Leu Lys Lys Tyr Arg Asn Met Val Val Arg Ala Cys Gly Cys His420 425 430<210>21<211>417<212>DNA<213>智人(Homo sapiens)<400>21tccacgggga gcaaacagcg cagccagaac cgctccaaga cgcccaagaa ccaggaagcc 60ctgcggatgg ccaacgtggc agagaacagc agcagcgacc agaggcaggc ctgtaagaag120cacgagctgt atgtcagctt ccgagacctg ggctggcagg actggatcat cgcgcctgaa180ggctacgccg cctactactg tgagggggag tgtgccttcc ctctgaactc ctacatgaac240gccaccaacc acgccatcgt gcagacgctg gtccacttca tcaacccgga aacggtgccc300aagccctgct gtgcgcccac gcagctcaat gccatctccg tcctctactt cgatgacagc360tccaacgtca tcctgaagaa atacagaaac atggtggtcc gggcctgtgg ctgccac 417<210>22<21l>139<212>PRT<213>智人(Homo sapiens)<400>22Ser Thr Gly Ser Lys Gln Arg Ser Gln Asn Arg Ser Lys Thr Pro Lys1 5 10 15Asn Gln Glu Ala Leu Arg Met Ala Asn Val Ala Glu Asn Ser Ser Ser20 25 30Asp Gln Arg Gln Ala Cys Lys Lys His Glu Leu Tyr Val Ser Phe Arg35 40 45Asp Leu Gly Trp Gln Asp Trp Ile Ile Ala Pro Glu Gly Tyr Ala Ala50 55 60Tyr Tyr Cys Glu Gly Glu Cys Ala Phe Pro Leu Asn Ser Tyr Met Asn65 70 75 80Ala Thr Asn His Ala Ile Val Gln Thr Leu Val His Phe Ile Asn Pro85 90 95Glu Thr Val Pro Lys Pro Cys Cys Ala Pro Thr Gln Leu Asn Ala Ile100 105 110
Ser Val Leu Tyr Phe Asp Asp Ser Ser Asn Val Ile Leu Lys Lys Tyr115 120 125Arg Asn Met Val Val Arg Ala Cys Gly Cys His130 135<210>23<211>3536<212>DNA<213>智人(Homo sapiens)<400>23ccgcccgtcc cgccccgccc cgccgcccgc cgcccgccga gcccagcctc cttgccgtcg60gggcgtcccc aggccctggg tcggccgcgg agccgatgcg cgcccgctga gcgccccagc 120tgagcgcccc cggcctgcca tgaccgcgct ccccggcccg ctctggctcc tgggcctggc 180gctatgcgcg ctgggcgggg gcggccccgg cctgcgaccc ccgcccggct gtccccagcg 240acgtctgggc gcgcgcgagc gccgggacgt gcagcgcgag atcctggcgg tgctcgggct 300gcctgggcgg ccccggcccc gcgcgccacc cgccgcctcc cggctgcccg cgtccgcgcc 360gctcttcatg ctggacctgt accacgccat ggccggcgac gacgacgagg acggcgcgcc 420cgcggagcgg cgcctgggcc gcgccgacct ggtcatgagc ttcgttaaca tggtggagcg 480agaccgtgcc ctgggccacc aggagcccca ttggaaggag ttccgctttg acctgaccca 540gatcccggct ggggaggcgg tcacagctgc ggagttccgg atttacaagg tgcccagcat 600ccacctgctc aacaggaccc tccacgtcag catgttccag gtggtccagg agcagtccaa 660cagggagtct gacttgttct ttttggatct tcagacgctc cgagctggag acgagggctg 720gctggtgctg gatgtcacag cagccagtga ctgctggttg ctgaagcgtc acaaggacct 780gggactccgc ctctatgtgg agactgagga cgggcacagc gtggatcctg gcctggccgg 840cctgctgggt caacgggccc cacgctccca acagcctttc gtggtcactt tcttcagggc 900cagtccgagt cccatccgca cccctcgggc agtgaggcca ctgaggagga ggcagccgaa 960gaaaagcaac gagctgccgc aggccaaccg actcccaggg atctttgatg acgtccacgg 1020ctcccacggc cggcaggtct gccgtcggca cgagctctac gtcagcttcc aggacctcgg 1080ctggctggac tgggtcatcg ctccccaagg ctactcggcc tattactgtg agggggagtg 1140ctccttccca ctggactcct gcatgaatgc caccaaccac gccatcctgc agtccctggt 1200gcacctgatg atgccagacg cagtccccaa ggcgtgctgt gcacccacca agctgagcgc 1260cacctctgtg ctctactatg acagcagcaa caatgtcatc ctgcgcaagc accgcaacat 1320ggtggtcaag gcctgcggct gccactgagt ccacccgccc ggcccagctg cagccaccct 1380tctcatctgg atcgggcccc tcagaagcag gaaaccctca aacccagcca gaccccaggc 1440cggggcattg ccagggagga ccctcacaac cacgtacatg accctttctc cttcatgcca 1500ggctcctatg ctccccttgc cctgccaggc atttgtgtga ctgtcctgtt tccagcccag 1560gtggtctcaa tcatcaggca gtgttctacc caaatgcaaa cgcctctccc ggaggcatgt 1620cctggctggt tctttggggt tggcacagaa gtcctgtctg aggtcctatc catgcccctt 1680actggctcag gtcgtgagat agatgtggaa tgacctgaga ggcacctgga gcccactgtt 1740ggccaccttg agctcttcac catccatcac agggtgtggt gtgtgtagtc agggtctggt 1800tggctcccca ttgcctgccc gaggtgcaag gtggggtata aaactggata acccctgaag 1860tattgtatat tcatggatct gaagcactga tccactggtc acaggtagac atgtggagtc 1920aactcaagaa aaagctgagt gaacagcatg atttagggct aaagccaatg gcatttatct 1980tcccttgtct tcctgctttg catttgcctc tgccatctag gaaagacatg taagagcatg 2040gacattttac tttggagaaa cagaaaaatc ttggggcttc caattgaccc atctatctgc 2100caccatgttg ccccaccagg agctcagctc tgtggagttt tccctttgct gagcaagcat 2160gtggttgcat tgggtggccc aggatgacaa tgcacagcac agatgccatc atttcccttt 2220cccctctgaa tggcagacat cagtaatcaa tctggaatgt ttttcttcca aatctgagtg 2280gaattttcaa atgatcagca cagccactgc caacagatat gatgtaaagt gaaacctggt 2340
tgccatcttc tgccatgctg aggagcagtc catccctgcc cgagcatgta tcggcaacat 2400gggcagcctg tgaccgggtc tggggcgagg ccaggggcca tcaaaaacag gctgatcacc 2460aaagtcagtg tcaccctgga tgcccagcag ccctgtcctg tgtcttgggc ctgtgagtca 2520aagaaaaggt ccttttcagg gagtgacaag tagtaattag gctgagttgg gtggagaggt 2580ttgtctcagc ctctgctgtt ctcggaaact gctgttctcc ttggagcagc cactgggagt 2640tggagtgttt atttgatttc tgacttgcta agcctgtaat ttacctgctg gaatagacag 2700agtccagctg cccaaaccgt gtcattaaaa gcagatcctg cgcccgcccc atccacaggc 2760acagcccggc agagtggttc cacctcccca tgggcccaag gatgcgcctc tctggagttc 2820acgtgctgca cccccaggga ggggcctggg gaaagctggt ccagcagcag gggtggaggc 2880tggggccaca ctgcgggaca gcagcccctc cacctggacc agggagggcc tccatgtgca 2940agcgcagagg aagagaccct cccatgtacg caaagggcag ccccaggctg tctggaagtt 3000ggagaattcc ctatcagcac agggatctca gctctggcct ggaggtgaag agacctgcct 3060tgtaggtggc ttccttatct gcgcctccat tttctatctg cactttttga tctccaaaca 3120accttcagcc aaagaatctg tctaccaact cctcatagtg agccagaagc agcctcataa 3180ccctgaatgt ggggctctgg tggctgtcac gaagcagagt tggcacataa catggaacct 3240ggccaggcat ggtggctcac acctataacc ccagcacttt gggaggccaa ggcaggcaga 3300tcacctgaag tcaggagttc aagaccatcc tggccaacac agtgaaaccc catctgtact 3360aaaaatacaa gattacctgg gcatggtggt gcatgcctat aatcccagct actcaggagg 3420ctgaggcaga attgcttgaa cctgggaggt ggaggttgca gtgagcagag atcacaacat 3480tgcacttcag cctggtgaca tgagcaaaac tgttgtctca acaaaatgaa attatg 3536<210>24<211>402<212>PRT<213>智人(Homo sapiens)<400>24Met Thr Ala Leu Pro Gly Pro Leu Trp Leu Leu Gly Leu Ala Leu Cys1 5 10 15Ala Leu Gly Gly Gly Gly Pro Gly Leu Arg Pro Pro Pro Gly Cys Pro20 25 30Gln Arg Arg Leu Gly Ala Arg Glu Arg Arg Asp Val Gln Arg Glu Ile35 40 45Leu Ala Val Leu Gly Leu Pro Gly Arg Pro Arg Pro Arg Ala Pro Pro50 55 60Ala Ala Ser Arg Leu Pro Ala Ser Ala Pro Leu Phe Met Leu Asp Leu65 70 75 80Tyr His Ala Met Ala Gly Asp Asp Asp Glu Asp Gly Ala Pro Ala Glu85 90 95Arg Arg Leu Gly Arg Ala Asp Leu Val Met Ser Phe Val Asn Met Val100 105 110Glu Arg Asp Arg Ala Leu Gly His Gln Glu Pro His Trp Lys Glu Phe115 120 125Arg Phe Asp Leu Thr Gln Ile Pro Ala Gly Glu Ala Val Thr Ala Ala
130 135 140Glu Phe Arg Ile Tyr Lys Val Pro Ser Ile His Leu Leu Asn Arg Thr145 150 155 160Leu His Val Ser Met Phe Gln Val Val Gln Glu Gln Ser Asn Arg Glu165 170 175Ser Asp Leu Phe Phe Leu Asp Leu Gln Thr Leu Arg Ala Gly Asp Glu180 185 190Gly Trp Leu Val Leu Asp Val Thr Ala Ala Ser Asp Cys Trp Leu Leu195 200 205Lys Arg His Lys Asp Leu Gly Leu Arg Leu Tyr Val Glu Thr Glu Asp210 215 220Gly His Ser Val Asp Pro Gly Leu Ala Gly Leu Leu Gly Gln Arg Ala225 230 235 240Pro Arg Ser Gln Gln Pro Phe Val Val Thr Phe Phe Arg Ala Ser Pro245 250 255Ser Pro Ile Arg Thr Pro Arg Ala Val Arg Pro Leu Arg Arg Arg Gln260 265 270Pro Lys Lys Ser Asn Glu Leu Pro Gln Ala Asn Arg Leu Pro Gly Ile275 280 285Phe Asp Asp Val His Gly Ser His Gly Arg Gln Val Cys Arg Arg His290 295 300Glu Leu Tyr Val Ser Phe Gln Asp Leu Gly Trp Leu Asp Trp Val Ile305 310 315 320Ala Pro Gln Gly Tyr Ser Ala Tyr Tyr Cys Glu Gly Glu Cys Ser Phe325 330 335Pro Leu Asp Ser Cys Met Asn Ala Thr Asn His Ala Ile Leu Gln Ser340 345 350Leu Val His Leu Met Met Pro Asp Ala Val Pro Lys Ala Cys Cys Ala355 360 365Pro Thr Lys Leu Ser Ala Thr Ser Val Leu Tyr Tyr Asp Ser Ser Asn370 375 380Asn Val Ile Leu Arg Lys His Arg Asn Met Val Val Lys Ala Cys Gly385 390 395 400Cys His
<210>25<211>417<212>DNA<213>智人(Homo sapiens)<400>25gcagtgaggc cactgaggag gaggcagccg aagaaaagca acgagctgcc gcaggccaac 60cgactcccag ggatctttga tgacgtccac ggctcccacg gccggcaggt ctgccgtcgg 120cacgagctct acgtcagctt ccaggacctc ggctggctgg actgggtcat cgctccccaa 180ggctactcgg cctattactg tgagggggag tgctccttcc cactggactc ctgcatgaat 240gccaccaacc acgccatcct gcagtccctg gtgcacctga tgatgccaga cgcagtcccc 300aaggcgtgct gtgcacccac caagctgagc gccacctctg tgctctacta tgacagcagc 360aacaatgtca tcctgcgcaa gcaccgcaac atggtggtca aggcctgcgg ctgccac 417<210>26<211>139<212>PRT<213>智人(Homo sapiens)<400>26Ala Val Arg Pro Leu Arg Arg Arg Gln Pro Lys Lys Ser Asn Glu Leu1 5 10 15Pro Gln Ala Asn Arg Leu Pro Gly Ile Phe Asp Asp Val His Gly Ser20 25 30His Gly Arg Gln Val Cys Arg Arg His Glu Leu Tyr Val Ser Phe Gln35 40 45Asp Leu Gly Trp Leu Asp Trp Val Ile Ala Pro Gln Gly Tyr Ser Ala50 55 60Tyr Tyr Cys Glu Gly Glu Cys Ser Phe Pro Leu Asp Ser Cys Met Asn65 70 75 80Ala Thr Asn His Ala Ile Leu Gln Ser Leu Val His Leu Met Met Pro85 90 95Asp Ala Val Pro Lys Ala Cys Cys Ala Pro Thr Lys Leu Ser Ala Thr100 105 110Ser Val Leu Tyr Tyr Asp Ser Ser Asn Asn Val Ile Leu Arg Lys His115 120 125Arg Asn Met Val Val Lys Ala Cys Gly Cys His130 135<210>27<211>1942<212>DNA<213>智人(Homo sapiens)
<400>27cggtccagcc cggcagcggg tgagagtggg tgctggccag gacggttcct tcagagcaaa 60cagcagggag atgccggccc gctccttccc agctcctccc cgtgcccgct aacacagcac120ggccgcctgc agtctcctct ctgggtgatt gcgcgggcct aagatgtgtc ctggggcact180gtgggtggcc ctgcccctgc tgtccctgct ggctggctcc ctacagggga agccactgca240gagctgggga cgagggtctg ctgggggaaa cgcccacagc ccactggggg tgcctggagg300tgggctgcct gagcacacct tcaacctgaa gatgtttctg gagaacgtga aggtggattt360cctgcgcagc cttaacctga gtggggtccc ttcgcaggac aaaaccaggg tggagccgcc420gcagtacatg attgacctgt acaacaggta cacgtccgat aagtcgacta cgccagcgtc480caacattgtg cggagcttca gcatggaaga tgccatctcc ataactgcca cagaggactt540ccccttccag aagcacatct tgctcttcaa catctccatt cctaggcatg agcagatcac600cagagctgag ctccgactct atgtctcctg tcaaaatcac gtggacccct ctcatgacct660gaaaggaagc gtggtcattt atgatgttct ggatggaaca gatgcctggg atagtgctac720agagaccaag accttcctgg tgtcccagga cattcaggat gagggctggg agaccttgga780agtgtccagc gccgtgaagc gctgggtccg gtccgactcc accaagagca aaaataagct840ggaagtgact gtggagagcc acaggaaggg ctgcgacacg ctggacatca gtgtcccccc900aggttccaga aacctgccct tctttgttgt cttctccaat gaccacagca gtgggaccaa960ggagaccagg ctggagctga gggagatgat cagccatgaa caagagagcg tgctcaagaa 1020gctgtccaag gacggctcca cagaggcagg tgagagcagt cacgaggagg acacggatgg 1080ccacgtggct gcggggtcga ctttagccag gcggaaaagg agcgccgggg ctggcagcca 1140ctgtcaaaag acctccctgc gggtaaactt cgaggacatc ggctgggaca gctggatcat 1200tgcacccaag gagtatgaag cctacgagtg taagggcggc tgcttcttcc ccttggctga 1260cgatgtgacg ccgacgaaac acgctatcgt gcagaccctg gtgcatctca agttccccac 1320aaaggtgggc aaggcctgct gtgtgcccac caaactgagc cccatctccg tcctctacaa 1380ggatgacatg ggggtgccca ccctcaagta ccattacgag ggcatgagcg tggcagagtg 1440tgggtgcagg tagtatctgc ctgcggggct ggggaggcag gccaaagggg ctccacatga 1500gaggtcctgc atgcccctgg gcacaacaag gactgattca atctgcatgc cagcctggag 1560gaggaaaggg agcctgctct ccctccccac accccaccca aagcatacac cgctgagctc 1620aactgccagg gaaggctaag gaaatgggga tttgagcaca acaggaaagc ctgggagggt 1680tgttgggatg caaggaggtg atgaaaagga gacaggggga aaaataatcc atagtcagca 1740gaaaacaaca gcagtgagcc agaggagcac aggcgggcag gtcactgcag agactgatgg 1800aagttagaga ggtggaggag gccagctcgc tccaaaaccc ttggggagta gagggaagga 1860gcaggccgcg tgtcacaccc atcattgtat gttatttccc acaacccagt tggaggggca 1920tggcttccaa tttagagacc cg1942<210>28<211>429<212>PRT<213>智人(Homo sapiens)<400>28Met Cys Pro Gly Ala Leu Trp Val Ala Leu Pro Leu Leu Ser Leu Leu1 5 10 15Ala Gly Ser Leu Gln Gly Lys Pro Leu Gln Ser Trp Gly Arg Gly Ser20 25 30Ala Gly Gly Asn Ala His Ser Pro Leu Gly Val Pro Gly Gly Gly Leu35 40 45Pro Glu His Thr Phe Asn Leu Lys Met Phe Leu Glu Asn Val Lys Val
50 55 60Asp Phe Leu Arg Ser Leu Asn Leu Ser Gly Val Pro Ser Gln Asp Lys65 70 75 80Thr Arg Val Glu Pro Pro Gln Tyr Met Ile Asp Leu Tyr Asn Arg Tyr85 90 95Thr Ser Asp Lys Ser Thr Thr Pro Ala Ser Asn Ile Val Arg Ser Phe100 105 110Ser Met Glu Asp Ala Ile Ser Ile Thr Ala Thr Glu Asp Phe Pro Phe115 120 125Gln Lys His Ile Leu Leu Phe Asn Ile Ser Ile Pro Arg His Glu Gln130 135 140Ile Thr Arg Ala Glu Leu Arg Leu Tyr Val Ser Cys Gln Asn His Val145 150 155 160Asp Pro Ser His Asp Leu Lys Gly Ser Val Val Ile Tyr Asp Val Leu165 170 175Asp Gly Thr Asp Ala Trp Asp Ser Ala Thr Glu Thr Lys Thr Phe Leu180 185 190Val Ser Gln Asp Ile Gln Asp Glu Gly Trp Glu Thr Leu Glu Val Ser195 200 205Ser Ala Val Lys Arg Trp Val Arg Ser Asp Ser Thr Lys Ser Lys Asn210 215 220Lys Leu Glu Val Thr Val Glu Ser His Arg Lys Gly Cys Asp Thr Leu225 230 235 240Asp Ile Ser Val Pro Pro Gly Ser Arg Asn Leu Pro Phe Phe Val Val245 250 255Phe Ser Asn Asp His Ser Ser Gly Thr Lys Glu Thr Arg Leu Glu Leu260 265 270Arg Glu Met Ile Ser His Glu Gln Glu Ser Val Leu Lys Lys Leu Ser275 280 285Lys Asp Gly Ser Thr Glu Ala Gly Glu Ser Ser His Glu Glu Asp Thr290 295 300Asp Gly His Val Ala Ala Gly Ser Thr Leu Ala Arg Arg Lys Arg Ser305 310 315 320Ala Gly Ala Gly Ser His Cys Gln Lys Thr Ser Leu Arg Val Asn Phe325 330 335
Glu Asp Ile Gly Trp Asp Ser Trp Ile Ile Ala Pro Lys Glu Tyr Glu340 345 350Ala Tyr Glu Cys Lys Gly Gly Cys Phe Phe Pro Leu Ala Asp Asp Val355 360 365Thr Pro Thr Lys His Ala Ile Val Gln Thr Leu Val His Leu Lys Phe370 375 380Pro Thr Lys Val Gly Lys Ala Cys Cys Val Pro Thr Lys Leu Ser Pro385 390 395 400Ile Ser Val Leu Tyr Lys Asp Asp Met Gly Val Pro Thr Leu Lys Tyr405 410 415His Tyr Glu Gly Met Ser Val Ala Glu Cys Gly Cys Arg420 425<210>29<211>1584<212>DNA<213>智人(Homo sapiens)<400>29ggggagagga agagtggtag ggggagggag agagagagga agagtttcca aacttgtctc 60cagtgacagg agacatttac gttccacaag ataaaactgc cacttagagc ccagggaagc120taaaccttcc tggcttggcc taggagctcg agcggagtca tgggctctct ggtcctgaca180ctgtgcgctc ttttctgcct ggcagcttac ttggtttctg gcagccccat catgaaccta240gagcagtctc ctctggaaga agatatgtcc ctctttggtg atgttttctc agagcaagac300ggtgtcgact ttaacacact gctccagagc atgaaggatg agtttcttaa gacactaaac360ctctctgaca tccccacgca ggattcagcc aaggtggacc caccagagta catgttggaa420ctctacaaca aatttgcaac agatcggacc tccatgccct ctgccaacat cattaggagt480ttcaagaatg aagatctgtt ttcccagccg gtcagtttta atgggctccg aaaatacccc540ctcctcttca atgtgtccat tcctcaccat gaagaggtca tcatggctga acttaggcta600tacacactgg tgcaaaggga tcgtatgata tacgatggag tagaccggaa aattaccatt660tttgaagtgc tggagagcaa aggggataat gagggagaaa gaaacatgct ggtcttggtg720tctggggaga tatatggaac caacagtgag tgggagactt ttgatgtcac agatgccatc780agacgttggc aaaagtcagg ctcatccacc caccagctgg aggtccacat tgagagcaaa840cacgatgaag ctgaggatgc cagcagtgga cggctagaaa tagataccag tgcccagaat900aagcataacc ctttgctcat cgtgttttct gatgaccaaa gcagtgacaa ggagaggaag960gaggaactga atgaaatgat ttcccatgag caacttccag agctggacaa cttgggcctg 1020gatagctttt ccagtggacc tggggaagag gctttgttgc agatgagatc aaacatcatc 1080tatgactcca ctgcccgaat cagaaggaac gccaaaggaa actactgtaa gaggaccccg 1140ctctacatcg acttcaagga gattgggtgg gactcctgga tcatcgctcc gcctggatac 1200gaagcctatg aatgccgtgg tgtttgtaac taccccctgg cagagcatct cacacccaca 1260aagcatgcaa ttatccaggc cttggtccac ctcaagaatt cccagaaagc ttccaaagcc 1320tgctgtgtgc ccacaaagct agagcccatc tccatcctct atttagacaa aggcgtcgtc 1380acctacaagt ttaaatacga aggcatggcc gtctccgaat gtggctgtag atagaagaag 1440agtcctatgg cttatttaat aactgtaaat gtgtatattt ggtgttccta tttaatgaga 1500ttatttaata agggtgtaca gtaatagagg cttgctgcct tcaggaaatg gacaggtcag 1560tttgttgtag gaaatgcata tttt 1584
<210>30<211>424<212>PRT<213>智人(Homo sapiens)<400>30Met Gly Ser Leu Val Leu Thr Leu Cys Ala Leu Phe Cys Leu Ala Ala1 5 10 15Tyr Leu Val Ser Gly Ser Pro Ile Met Asn Leu Glu Gln Ser Pro Leu20 25 30Glu Glu Asp Met Ser Leu Phe Gly Asp Val Phe Ser Glu Gln Asp Gly35 40 45Val Asp Phe Asn Thr Leu Leu Gln Ser Met Lys Asp Glu Phe Leu Lys50 55 60Thr Leu Asn Leu Ser Asp Ile Pro Thr Gln Asp Ser Ala Lys Val Asp65 70 75 80Pro Pro Glu Tyr Met Leu Glu Leu Tyr Asn Lys Phe Ala Thr Asp Arg85 90 95Thr Ser Met Pro Ser Ala Asn Ile Ile Arg Ser Phe Lys Asn Glu Asp100 105 110Leu Phe Ser Gln Pro Val Ser Phe Asn Gly Leu Arg Lys Tyr Pro Leu115 120 125Leu Phe Asn Val Ser Ile Pro His His Glu Glu Val Ile Met Ala Glu130 135 140Leu Arg Leu Tyr Thr Leu Val Gln Arg Asp Arg Met Ile Tyr Asp Gly145 150 155 160Val Asp Arg Lys Ile Thr Ile Phe Glu Val Leu Glu Ser Lys Gly Asp165 170 175Asn Glu Gly Glu Arg Asn Met Leu Val Leu Val Ser Gly Glu Ile Tyr180 185 190Gly Thr Asn Ser Glu Trp Glu Thr Phe Asp Val Thr Asp Ala Ile Arg195 200 205Arg Trp Gln Lys Ser Gly Ser Ser Thr His Gln Leu Glu Val His Ile210 215 220Glu Ser Lys His Asp Glu Ala Glu Asp Ala Ser Ser Gly Arg Leu Glu225 230 235 240
Ile Asp Thr Ser Ala Gln Asn Lys His Asn Pro Leu Leu Ile Val Phe245 250 255Ser Asp Asp Gln Ser Ser Asp Lys Glu Arg Lys Glu Glu Leu Asn Glu260 265 270Met Ile Ser His Glu Gln Leu Pro Glu Leu Asp Asn Leu Gly Leu Asp275 280 285Ser Phe Ser Ser Gly Pro Gly Glu Glu Ala Leu Leu Gln Met Arg Ser290 295 300Asn Ile Ile Tyr Asp Ser Thr Ala Arg Ile Arg Arg Asn Ala Lys Gly305 310 315 320Asn Tyr Cys Lys Arg Thr Pro Leu Tyr Ile Asp Phe Lys Glu Ile Gly325 330 335Trp Asp Ser Trp Ile Ile Ala Pro Pro Gly Tyr Glu Ala Tyr Glu Cys340 345 350Arg Gly Val Cys Asn Tyr Pro Leu Ala Glu His Leu Thr Pro Thr Lys355 360 365His Ala Ile Ile Gln Ala Leu Val His Leu Lys Asn Ser Gln Lys Ala370 375 380Ser Lys Ala Cys Cys Val Pro Thr Lys Leu Glu Pro Ile Ser Ile Leu385 390 395 400Tyr Leu Asp Lys Gly Val Val Thr Tyr Lys Phe Lys Tyr Glu Gly Met405 410 415Ala Val Ser Glu Cys Gly Cys Arg420<210>31<211>324<212>DNA<213>智人(Homo sapiens)<400>31aacgccaaag gaaactactg taagaggacc ccgctctaca tcgacttcaa ggagattggg 60tgggactcct ggatcatcgc tccgcctgga tacgaagcct atgaatgccg tggtgtttgt120aactaccccc tggcagagca tctcacaccc acaaagcatg caattatcca ggccttggtc180cacctcaaga attcccagaa agcttccaaa gcctgctgtg tgcccacaaa gctagagccc240atctccatcc tctatttaga caaaggcgtc gtcacctaca agtttaaata cgaaggcatg300gccgtctccg aatgtggctg taga 324<210>32<211>108<212>PRT
<213>智人(Homo sapiens)<400>32Asn Ala Lys Gly Asn Tyr Cys Lys Arg Thr Pro Leu Tyr Ile Asp Phe1 5 10 15Lys Glu Ile Gly Trp Asp Ser Trp Ile Ile Ala Pro Pro Gly Tyr Glu20 25 30Ala Tyr Glu Cys Arg Gly Val Cys Asn Tyr Pro Leu Ala Glu His Leu35 40 45Thr Pro Thr Lys His Ala Ile Ile Gln Ala Leu Val His Leu Lys Asn50 55 60Ser Gln Lys Ala Ser Lys Ala Cys Cys Val Pro Thr Lys Leu Glu Pro65 70 75 80Ile Ser Ile Leu Tyr Leu Asp Lys Gly Val Val Thr Tyr Lys Phe Lys85 90 95Tyr Glu Gly Met Ala Val Ser Glu Cys Gly Cys Arg100 105<210>33<211>1443<212>DNA<213>智人(Homo sapiens)<400>33tctccgcccc ccagtacctc cctcccctcc cctccagcat ggtgctcgcg gccccgctgc 60tgctgggctt cctgctcctc gccctggagc tgcggccccg gggggaggcg gccgagggcc120ccgcggcggc ggcggcggcg gcggcggcgg cggcagcggc gggggtcggg ggggagcgct180ccagccggcc agccccgtcc gtggcgcccg agccggacgg ctgccccgtg tgcgtttggc240ggcagcacag ccgcgagctg cgcctagaga gcatcaagtc gcagatcttg agcaaactgc300ggctcaagga ggcgcccaac atcagccgcg aggtggtgaa gcagctgctg cccaaggcgc360cgccgctgca gcagatcctg gacctacacg acttccaggg cgacgcgctg cagcccgagg420acttcctgga ggaggacgag taccacgcca ccaccgagac cgtcattagc atggcccagg480agacggaccc agcagtacag acagatggca gccctctctg ctgccatttt cacttcagcc540ccaaggtgat gttcacaaag gtactgaagg cccagctgtg ggtgtaccta cggcctgtac600cccgcccagc cacagtctac ctgcagatct tgcgactaaa acccctaact ggggaaggga660ccgcaggggg agggggcgga ggccggcgtc acatccgtat ccgctcactg aagattgagc720tgcactcacg ctcaggccat tggcagagca tcgacttcaa gcaagtgcta cacagctggt780tccgccagcc acagagcaac tggggcatcg agatcaacgc ctttgatccc agtggcacag840acctggctgt cacctccctg gggccgggag ccgaggggct gcatccattc atggagcttc900gagtcctaga gaacacaaaa cgttcccggc ggaacctggg tctggactgc gacgagcact960caagcgagtc ccgctgctgc cgatatcccc tcacagtgga ctttgaggct ttcggctggg 1020actggatcat cgcacctaag cgctacaagg ccaactactg ctccggccag tgcgagtaca 1080tgttcatgca aaaatatccg catacccatt tggtgcagca ggccaatcca agaggctctg 1140ctgggccctg ttgtaccccc accaagatgt ccccaatcaa catgctctac ttcaatgaca 1200agcagcagat tatctacggc aagatccctg gcatggtggt ggatcgctgt ggctgctctt 1260aaggtggggg atagaggatg cctcccccac agaccctacc ccaagacccc tagccctgcc 1320
cccatccccc caagccctag agctccctcc actcttcccg cgaacatcac accgttcccc 1380gaccaagccg tgtgcaatac aacagaggga ggcaggtggg aattgagggt gaggggtttg 1440ggg1443<210>34<211>407<212>PRT<213>智人(Homo sapiens)<400>34Met Val Leu Ala Ala Pro Leu Leu Leu Gly Phe Leu Leu Leu Ala Leu1 5 10 15Glu Leu Arg Pro Arg Gly Glu Ala Ala Glu Gly Pro Ala Ala Ala Ala20 25 30Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Val Gly Gly Glu Arg Ser35 40 45Ser Arg Pro Ala Pro Ser Val Ala Pro Glu Pro Asp Gly Cys Pro Val50 55 60Cys Val Trp Arg Gln His Ser Arg Glu Leu Arg Leu Glu Ser Ile Lys65 70 75 80Ser Gln Ile Leu Ser Lys Leu Arg Leu Lys Glu Ala Pro Asn Ile Ser85 90 95Arg Glu Val Val Lys Gln Leu Leu Pro Lys Ala Pro Pro Leu Gln Gln100 105 110Ile Leu Asp Leu His Asp Phe Gln Gly Asp Ala Leu Gln Pro Glu Asp115 120 125Phe Leu Glu Glu Asp Glu Tyr His Ala Thr Thr Glu Thr Val Ile Ser130 135 140Met Ala Gln Glu Thr Asp Pro Ala Val Gln Thr Asp Gly Ser Pro Leu145 150 155 160Cys Cys His Phe His Phe Ser Pro Lys Val Met Phe Thr Lys Val Leu165 170 175Lys Ala Gln Leu Trp Val Tyr Leu Arg Pro Val Pro Arg Pro Ala Thr180 185 190Val Tyr Leu Gln Ile Leu Arg Leu Lys Pro Leu Thr Gly Glu Gly Thr195 200 205Ala Gly Gly Gly Gly Gly Gly Arg Arg His Ile Arg Ile Arg Ser Leu210 215 220
Lys Ile Glu Leu His Ser Arg Ser Gly His Trp Gln Ser Ile Asp Phe225 230 235 240Lys Gln Val Leu His Ser Trp Phe Arg Gln Pro Gln Ser Asn Trp Gly245 250 255Ile Glu Ile Asn Ala Phe Asp Pro Ser Gly Thr Asp Leu Ala Val Thr260 265 270Ser Leu Gly Pro Gly Ala Glu Gly Leu His Pro Phe Met Glu Leu Arg275 280 285Val Leu Glu Asn Thr Lys Arg Ser Arg Arg Asn Leu Gly Leu Asp Cys290 295 300Asp Glu His Ser Ser Glu Ser Arg Cys Cys Arg Tyr Pro Leu Thr Val305 310 315 320Asp Phe Glu Ala Phe Gly Trp Asp Trp Ile Ile Ala Pro Lys Arg Tyr325 330 335Lys Ala Asn Tyr Cys Ser Gly Gln Cys Glu Tyr Met Phe Met Gln Lys340 345 350Tyr Pro His Thr His Leu Val Gln Gln Ala Asn Pro Arg Gly Ser Ala355 360 365Gly Pro Cys Cys Thr Pro Thr Lys Met Ser Pro Ile Asn Met Leu Tyr370 375 380Phe Asn Asp Lys Gln Gln Ile Ile Tyr Gly Lys Ile Pro Gly Met Val385 390 395 400Val Asp Arg Cys Gly Cys Ser405<210>35<211>1456<212>DNA<213>智人(Homo sapiens)<400>35cccggagcca cggagcccgc gccgcccgcc cgcccggccc acggagccca tggacctgag 60cgccgccgcc gcgctgtgcc tttggctgct gagcgcctgc cgcccccgcg acgggctgga120agcggccgcc gtgctgcgag cggcgggggc tgggccggtc cggagcccag ggggcggcgg180cggcggcggc ggcggcggcg gcggcgggcg gactcttgcc caggctgcgg gcgccgcggc240tgtcccggcc gccgcggttc cccgggcccg cgccgcgcgc cgcgccgcgg gctccggctt300caggaacggc tcggtggtgc cgcaccactt catgatgtcg ctttaccgga gcctggccgg360gagggctccg gccggggcag ccgctgtctc cgcctcgggc catggtcgcg cggacacgat420caccggcttc acagaccagg cgacccaaga cgaatcggca gccgaaacag gccagagctt480cctgttcgac gtgtccagcc ttaacgacgc agacgaggtg gtgggtgccg agctgcgcgt540gctgcgccgg ggatctccag agtcgggccc aggcagctgg acttctccgc cgttgctgct600
gctgtccacg tgcccgggcg ccgcccgagc gccacgcctg ctgtactcgc gggcagctga 660gcccctagtc ggtcagcgct gggaggcgtt cgacgtggcg gacgccatga ggcgccaccg 720tcgtgaaccg cgcccccccc gcgcgttctg cctcttgctg cgcgcagtgg caggcccggt 780gccgagcccg ttggcactgc ggcgactggg cttcggctgg ccgggcggag ggggctctgc 840ggcagaggag cgcgcggtgc tagtcgtctc ctcccgcacg cagaggaaag agagcttatt 900ccgggagatc cgcgcccagg cccgcgcgct cggggccgct ctggcctcag agccgctgcc 960cgacccagga accggcaccg cgtcgccaag ggcagtcatt ggcggccgca gacggaggag 1020gacggcgttg gccgggacgc ggacagcgca gggcagcggc gggggcgcgg gccggggcca 1080cgggcgcagg ggccggagcc gctgcagccg caagccgttg cacgtggact tcaaggagct 1140cggctgggac gactggatca tcgcgccgct ggactacgag gcgtaccact gcgagggcct 1200ttgcgacttc cctttgcgtt cgcacctcga gcccaccaac catgccatca ttcagacgct 1260gctcaactcc atggcaccag acgcggcgcc ggcctcctgc tgtgtgccag cgcgcctcag 1320ccccatcagc atcctctaca tcgacgccgc caacaacgtt gtctacaagc aatacgagga 1380catggtggtg gaggcctgcg gctgcaggta gcgcgcgggc cggggagggg gcagccacgc 1440ggccgaggat ccccag 1456<210>36<211>453<212>PRT<213>智人(Homo sapiens)<400>36Met Asp Leu Ser Ala Ala Ala Ala Leu Cys Leu Trp Leu Leu Ser Ala1 5 10 15Cys Arg Pro Arg Asp Gly Leu Glu Ala Ala Ala Val Leu Arg Ala Ala20 25 30Gly Ala Gly Pro Val Arg Ser Pro Gly Gly Gly Gly Gly Gly Gly Gly35 40 45Gly Gly Gly Gly Gly Arg Thr Leu Ala Gln Ala Ala Gly Ala Ala Ala50 55 60Val Pro Ala Ala Ala Val Pro Arg Ala Arg Ala Ala Arg Arg Ala Ala65 70 75 80Gly Ser Gly Phe Arg Asn Gly Ser Val Val Pro His His Phe Met Met85 90 95Ser Leu Tyr Arg Ser Leu Ala Gly Arg Ala Pro Ala Gly Ala Ala Ala100 105 110Val Ser Ala Ser Gly His Gly Arg Ala Asp Thr Ile Thr Gly Phe Thr115 120 125Asp Gln Ala Thr Gln Asp Glu Ser Ala Ala Glu Thr Gly Gln Ser Phe130 135 140Leu Phe Asp Val Ser Ser Leu Asn Asp Ala Asp Glu Val Val Gly Ala145 150 155 160
Glu Leu Arg Val Leu Arg Arg Gly Ser Pro Glu Ser Gly Pro Gly Ser165 170 175Trp Thr Ser Pro Pro Leu Leu Leu Leu Ser Thr Cys Pro Gly Ala Ala180 185 190Arg Ala Pro Arg Leu Leu Tyr Ser Arg Ala Ala Glu Pro Leu Val Gly195 200 205Gln Arg Trp Glu Ala Phe Asp Val Ala Asp Ala Met Arg Arg His Arg210 215 220Arg Glu Pro Arg Pro Pro Arg Ala Phe Cys Leu Leu Leu Arg Ala Val225 230 235 240Ala Gly Pro Val Pro Ser Pro Leu Ala Leu Arg Arg Leu Gly Phe Gly245 250 255Trp Pro Gly Gly Gly Gly Ser Ala Ala Glu Glu Arg Ala Val Leu Val260 265 270Val Ser Ser Arg Thr Gln Arg Lys Glu Ser Leu Phe Arg Glu Ile Arg275 280 285Ala Gln Ala Arg Ala Leu Gly Ala Ala Leu Ala Ser Glu Pro Leu Pro290 295 300Asp Pro Gly Thr Gly Thr Ala Ser Pro Arg Ala Val Ile Gly Gly Arg305 310 315 320Arg Arg Arg Arg Thr Ala Leu Ala Gly Thr Arg Thr Ala Gln Gly Ser325 330 335Gly Gly Gly Ala Gly Arg Gly His Gly Arg Arg Gly Arg Ser Arg Cys340 345 350Ser Arg Lys Pro Leu His Val Asp Phe Lys Glu Leu Gly Trp Asp Asp355 360 365Trp Ile Ile Ala Pro Leu Asp Tyr Glu Ala Tyr His Cys Glu Gly Leu370 375 380Cys Asp Phe Pro Leu Arg Ser His Leu Glu Pro Thr Asn His Ala Ile385 390 395 400Ile Gln Thr Leu Leu Asn Ser Met Ala Pro Asp Ala Ala Pro Ala Ser405 410 415Cys Cys Val Pro Ala Arg Leu Ser Pro Ile Ser Ile Leu Tyr Ile Asp420 425 430Ala Ala Asn Asn Val Val Tyr Lys Gln Tyr Glu Asp Met Val Val Glu
435 440 445Ala Cys Gly Cys Arg450<210>37<211>4561<212>DNA<213>智人(Homo sapiens)<400>37atggatactc ccagggtcct gctctcggcc gtcttcctca tcagttttct gtgggatttg 60cccggtttcc agcaggcttc catctcatcc tcctcgtcgt ccgccgagct gggttccacc 120aagggcatgc gaagccgcaa ggaaggcaag atgcagcggg cgccgcgcga cagtgacgcg 180ggccgggagg gccaggaacc acagccgcgg cctcaggacg aaccccgggc tcagcagccc 240cgggcgcagg agccgccagg caggggtccg cgcgtggtgc cccacgagta catgctgtca 300atctacagga cttactccat cgctgagaag ctgggcatca atgccagctt tttccagtct 360tccaagtcgg ctaatacgat caccagcttt gtagacaggg gactagcctc cccaccccca 420tccccgccac tgcgctgtat gcccccgatc ctggagatag aggagggatt gcatgtgcac 480ccagtctggg gaggcctctg ttcccgagcc aaggcctcca gactagcagg accgagatcc 540acaagtaccg ctacaacccc ggaatgcggt ggagggctgg ggatgcgagc ggtccacagc 600gggaggagac gctgcatgac cacccggaca gcatcttcaa aggcgctgtc tcctccgcgt 660ctccgggttc tcagaaaatg cgaagaaagg cagttcgttg actgggaagg cgccttcgtg 720gaggacctgg ttgctcccct gggctcccgg gtgacttacc ggtcgacagt gcagggaagg 780ccgcccctag ccaacccccc agagacaaaa ggagtttcct taaagcgcct tggagctcct 840gataggactg gccctgtggt cagatcgtgc ccccacaaaa ggacaccaaa gtggggaaag 900aaacgaatcc ttaggcctct cagggctgca ctgccagcca gggagtcatt tgggttagca 960caagggctgt cactggcctt gacccctgca gaagaggaaa cctgcaagaa gggctggatc1020cttgatgtgg ctggggtgga ggtcatctgt tcacctggca ctgtgggagg gacagcagtg1080gtgacagggc ctcacaggac tgagaagaat cgggatgatg agcacctttc ctccactcac1140ttctggaatc ttgtggagag aagtggacca caaggactga agtccagaga actggatttc1200aaaggaagtc aagagaagga cagctgccag gaaacgaaga taagccctaa tccagcaatt1260gtaactggaa atgtttatat gtctaatgtt cagcaaacac cgttaacaga ggtcagcagg1320cagcaggcaa agtgtcttca gggtaacagt gcatggtgtt gtattcactc cccaggttgg1380atgcctcctc tgagctattt ctgtgatgca ggtttagaca ggttggggca tgtgcgtaag1440agtgaaccag ccagtgctac ggtcagcccc gagtacaaac tgggtgtggc agaggctcca1500gagccagtgc ccccgggcta catctggact gacgatctct cgcacactcc tctccggaga1560cagaagtatt tgtttgatgt gtccatgctc tcagacaaag aagagctggt gggcgcggag1620ctgcggctct ttcgccaggc gccctcagcg ccctgggggc caccagccgg gccgctccac1680gtgcagctct tcccttgcct ttcgccccta ctgctggacg cgcggaccct ggacccgcag1740ggggcgccgc cggccggctg ggaagtcttc gacgtgtggc agggcctgcg ccaccagccc1800tggaagcagc tgtgcttgga gctgcgggcc gcatggggcg agctggacgc cggggaggcc1860gaggcgcgcg cgcggggacc ccagcaaccg ccgcccccgg acctgcggag tctgggcttc1920ggccggaggg tgcggcctcc ccaggagcgg gccctgctgg tggtattcac cagatcccag1980cgcaagaacc tgttcgcaga gatgcgcgag cagctgggct cggccgaggc tgcgggcccg2040ggcgcgggcg ccgaggggtc gtggccgccg ccgtcgggcg ccccggatgc caggccttgg2100ctgccctcgc ccggccgccg gcggcggcgc acggccttcg ccagtcgcca tggcaagcgg2160cacggcaaga agtccaggct acgctgcagc aagaagcccc tgcacgtgaa cttcaaggag2220ctgggctggg acgactggat tatcgcgccc ctggagtacg aggcctatca ctgcgagggt2280gtatgcgact tcccgctgcg ctcgcacctg gagcccacca accacgccat catccagacg2340ctgatgaact ccatggaccc cggctccacc ccgcccagct gctgcgtgcc caccaaattg2400actcccatca gcattctata catcgacgcg ggcaataatg tggtctacaa gcagtacgag2460
gacatggtgg tggagtcgtg cggctgcagg tagcggtgcc tttcccgccg ccttggcccg 2520gaaccaaggt gggccaaggt ccgccttgca ggggaggcct ggctgcagag aggcggagga 2580ggaagctggc gctgggggag gctgagggtg agggaacagc ctggatgtga gagccggtgg 2640gagagaaggg agcgcagcct tcccagtaac ttctacctgc cagcccagag ggaaatatgg 2700attttcacac cttgcctggc caccctggaa aaacaagcca aggaggattt cttttgttct 2760gttttctctc tctctctctc tctctctctc tctctctctc tctctctctc tattactgtg 2820gctttggatt tccttatgtg tcttacaggc tttgatagaa ggggagggga ggagagatgc 2880atacccgttt ctcaactgct ccatggattg aaaaaataac agtttaaaaa gggaaacaat 2940gtgggaggaa gaatcaccgt tgacgcatct tgatttggtt ggtttttaca tgtgtaaaga 3000aggtggggtc tctggccatg tcatagccca tgtcttgtgc cctcccacac agaaagtgtt 3060agatagggaa attggcaaaa agaatagtta agtcaggaat ggtcctgcct atagaagagc 3120tttgagagag gtgggcccac gggtgcccct ctcacccatt tgtgtactct gtgagtttac 3180cagctctgcc ctggcctctt tcggtaccag gaactggcaa ccttcatctc actcctgagg 3240gcccaggtct ctgccttcat tgttgctttt tctggtgggg gcaaggggag ctggtatgga 3300tggaatgaca agaattagtc caaatggaac cccttgaagg ataatgagaa accacaaggc 3360ctgcctctga ctggggctga cacggaggtg cattagccca ggctggaggt agcccaccca 3420aatgcccttt ctgattctaa ttgatttctt tcaacagaat ttgccaaaat tcagacatgc 3480acttctaagg ggaaggtgat tttccagttc aaaaaaatgg gcaggagtgg ggaacaaaac 3540aattaacgta agagctacaa aggagggaaa aggaaccaag aagtagaagg agtcccatca 3600ggagggaaga tggtgggcct cagggaggat ggggatcaag ggacaggcca ggagccagga 3660gtggggaagg gagggatgaa aggggacaca agtccctgtc tctgaagttt ctttaaaatc 3720tgagttccct cccctctctt tgacattcct gaaagattac cagccagcaa tagcccaggg 3780ctcccccaaa agaattggtt cagattgtaa ttatcagtta ggcaatgttt ttaaaactta 3840gtaatgagaa actgtgaaaa gagccaagtg ttacattgag cttggggtgg gagatgggga 3900acaggcagtg aggaaggaga caggggtgga attcgtcttc tgggaggaag ctggagagag 3960cacagtgaaa ttgaaatacc cattcccaga tagtcaaaaa catgaacttt cccccagcct 4020gcaccagtat tgttttcaaa cattgcccat gagtaggccc tttgaagagt tagcttcctc 4080ctcatctttg actataaaat tgtttaatca atggaatttg taccagcctt ttaaaaagtt 4140ttagtttttc ctaagtgatt ttgctctctt ccaatctaaa cctgttgctt gtttggttca 4200gagaactaca aactgtcaaa gaaagggtgg ggatgataag aaatgctaat ataaaaatgc 4260taagtgaaaa aaagacttgg ccaggagaaa taatttaaaa tgcacatttg ctttggatgc 4320actgttgttc tgttaaggct gtatatattt gtttatttaa ggtgactgaa agtgcaaaga 4380ggaaatggac agcatgcaat tcatcctaat gtacaaaacg ttatatgcac tcaaatgtta 4440taatttctaa tatttttaaa gtttatattc gagttgtaca aagttaagca ttaatcagat 4500atttcatttt ttcataatgt taccattttc ttaaatatta ttacaaaatt ttaagtctgt 4560c 4561<210>38<211>830<212>PRT<213>智人(Homo sapiens)<400>38Met Asp Thr Pro Arg Val Leu Leu Ser Ala Val Phe Leu Ile Ser Phe1 5 10 15Leu Trp Asp Leu Pro Gly Phe Gln Gln Ala Ser Ile Ser Ser Ser Ser20 25 30Ser Ser Ala Glu Leu Gly Ser Thr Lys Gly Met Arg Ser Arg Lys Glu35 40 45
Gly Lys Met Gln Arg Ala Pro Arg Asp Ser Asp Ala Gly Arg Glu Gly50 55 60Gln Glu Pro Gln Pro Arg Pro Gln Asp Glu Pro Arg Ala Gln Gln Pro65 70 75 80Arg Ala Gln Glu Pro Pro Gly Arg Gly Pro Arg Val Val Pro His Glu85 90 95Tyr Met Leu Ser Ile Tyr Arg Thr Tyr Ser Ile Ala Glu Lys Leu Gly100 105 110Ile Asn Ala Ser Phe Phe Gln Ser Ser Lys Ser Ala Asn Thr Ile Thr115 120 125Ser Phe Val Asp Arg Gly Leu Ala Ser Pro Pro Pro Ser Pro Pro Leu130 135 140Arg Cys Met Pro Pro Ile Leu Glu Ile Glu Glu Gly Leu His Val His145 150 155 160Pro Val Trp Gly Gly Leu Cys Ser Arg Ala Lys Ala Ser Arg Leu Ala165 170 175Gly Pro Arg Ser Thr Ser Thr Ala Thr Thr Pro Glu Cys Gly Gly Gly180 185 190Leu Gly Met Arg Ala Val His Ser Gly Arg Arg Arg Cys Met Thr Thr195 200 205Arg Thr Ala Ser Ser Lys Ala Leu Ser Pro Pro Arg Leu Arg Val Leu210 215 220Arg Lys Cys Glu Glu Arg Gln Phe Val Asp Trp Glu Gly Ala Phe Val225 230 235 240Glu Asp Leu Val Ala Pro Leu Gly Ser Arg Val Thr Tyr Arg Ser Thr245 250 255Val Gln Gly Arg Pro Pro Leu Ala Asn Pro Pro Glu Thr Lys Gly Val260 265 270Ser Leu Lys Arg Leu Gly Ala Pro Asp Arg Thr Gly Pro Val Val Arg275 280 285Ser Cys Pro His Lys Arg Thr Pro Lys Trp Gly Lys Lys Arg Ile Leu290 295 300Arg Pro Leu Arg Ala Ala Leu Pro Ala Arg Glu Ser Phe Gly Leu Ala305 310 315 320Gln Gly Leu Ser Leu Ala Leu Thr Pro Ala Glu Glu Glu Thr Cys Lys
325 330 335Lys Gly Trp Ile Leu Asp Val Ala Gly Val Glu Val Ile Cys Ser Pro340 345 350Gly Thr Val Gly Gly Thr Ala Val Val Thr Gly Pro His Arg Thr Glu355 360 365Lys Asn Arg Asp Asp Glu His Leu Ser Ser Thr His Phe Trp Asn Leu370 375 380Val Glu Arg Ser Gly Pro Gln Gly Leu Lys Ser Arg Glu Leu Asp Phe385 390 395 400Lys Gly Ser Gln Glu Lys Asp Ser Cys Gln Glu Thr Lys Ile Ser Pro405 410 415Asn Pro Ala Ile Val Thr Gly Asn Val Tyr Met Ser Asn Val Gln Gln420 425 430Thr Pro Leu Thr Glu Val Ser Arg Gln Gln Ala Lys Cys Leu Gln Gly435 440 445Asn Ser Ala Trp Cys Cys Ile His Ser Pro Gly Trp Met Pro Pro Leu450 455 460Ser Tyr Phe Cys Asp Ala Gly Leu Asp Arg Leu Gly His Val Arg Lys465 470 475 480Ser Glu Pro Ala Ser Ala Thr Val Ser Pro Glu Tyr Lys Leu Gly Val485 490 495Ala Glu Ala Pro Glu Pro Val Pro Pro Gly Tyr Ile Trp Thr Asp Asp500 505 510Leu Ser His Thr Pro Leu Arg Arg Gln Lys Tyr Leu Phe Asp Val Ser515 520 525Met Leu Ser Asp Lys Glu Glu Leu Val Gly Ala Glu Leu Arg Leu Phe530 535 540Arg Gln Ala Pro Ser Ala Pro Trp Gly Pro Pro Ala Gly Pro Leu His545 550 555 560Val Gln Leu Phe Pro Cys Leu Ser Pro Leu Leu Leu Asp Ala Arg Thr565 570 575Leu Asp Pro Gln Gly Ala Pro Pro Ala Gly Trp Glu Val Phe Asp Val580 585 590Trp Gln Gly Leu Arg His Gln Pro Trp Lys Gln Leu Cys Leu Glu Leu595 600 605
Arg Ala Ala Trp Gly Glu Leu Asp Ala Gly Glu Ala Glu Ala Arg Ala610 615 620Arg Gly Pro Gln Gln Pro Pro Pro Pro Asp Leu Arg Ser Leu Gly Phe625 630 635 640Gly Arg Arg Val Arg Pro Pro Gln Glu Arg Ala Leu Leu Val Val Phe645 650 655Thr Arg Ser Gln Arg Lys Asn Leu Phe Ala Glu Met Arg Glu Gln Leu660 665 670Gly Ser Ala Glu Ala Ala Gly Pro Gly Ala Gly Ala Glu Gly Ser Trp675 680 685Pro Pro Pro Ser Gly Ala Pro Asp Ala Arg Pro Trp Leu Pro Ser Pro690 695 700Gly Arg Arg Arg Arg Arg Thr Ala Phe Ala Ser Arg His Gly Lys Arg705 710 715 720His Gly Lys Lys Ser Arg Leu Arg Cys Ser Lys Lys Pro Leu His Val725 730 735Asn Phe Lys Glu Leu Gly Trp Asp Asp Trp Ile Ile Ala Pro Leu Glu740 745 750Tyr Glu Ala Tyr His Cys Glu Gly Val Cys Asp Phe Pro Leu Arg Ser755 760 765His Leu Glu Pro Thr Asn His Ala Ile Ile Gln Thr Leu Met Asn Ser770 775 780Met Asp Pro Gly Ser Thr Pro Pro Ser Cys Cys Val Pro Thr Lys Leu785 790 795 800Thr Pro Ile Ser Ile Leu Tyr Ile Asp Ala Gly Asn Asn Val Val Tyr805 810 815Lys Gln Tyr Glu Asp Met Val Val Glu Ser Cys Gly Cys Arg820 825 830<210>39<211>1179<212>DNA<213>智人(Homo sapiens)<400>39atggtcctcc tcagtattct tagaattctt tttctttgtg aactcgtgct tttcatggaa 60cacagggccc aaatggcaga aggagggcag tcctctattg cccttctggc tgaggcccct120actttgcccc tgattgagga gctgctagaa gaatcccctg gcgaacagcc aaggaagccc180
cggctcctag ggcattcact gcggtacatg ctggagttgt accggcgttc agctgactcg240catgggcacc ctagagagaa ccgcaccatt ggggccacca tggtgaggct ggtgaagccc300ttgaccagtg tggcaaggcc tcacagaggt acctggcata tacagatcct gggctttcct360ctcagaccaa accgaggact ataccaacta gttagagcca ctgtggttta ccgccatcat420ctccaactaa ctcgcttcaa tctctcctgc catgtggagc cctgggtgca gaaaaaccca480accaaccact tcccttcctc agaaggagat tcctcaaaac cttccctgat gtctaacgct540tggaaagaga tggatatcac acaacttgtt cagcaaaggt tctggaataa caagggacac600aggatcctac gactccgttt tatgtgtcag cagcaaaaag atagtggtgg tcttgagctc660tggcatggca cttcatcctt ggacattgcc ttcttgttac tctatttcaa tgatactcat720aaaagcattc ggaaggctaa atttcttccc aggggcatgg aggagttcat ggaaagggaa780tctcttctcc ggagaacccg acaagcagat ggtatctcag ctgaggttac tgcctcttcc840tcaaaacata gcgggcctga aaataaccag tgttccctcc accctttcca aatcagcttc900cgccagctgg gttgggatca ctggatcatt gctccccctt tctacacccc aaactactgt960aaaggaactt gtctccgagt actacgcgat ggtctcaatt cccccaatca cgccattatt 1020cagaacctta tcaatcagtt ggtggaccag agtgtccccc ggccctcctg tgtcccgtat 1080aagtatgttc caattagtgt ccttatgatt gaggcaaatg ggagtatttt gtacaaggag 1140tatgagggta tgattgctga gtcttgtaca tgcagatga 1179<210>40<21l>392<212>PRT<213>智人(Homo sapiens)<400>40Met Val Leu Leu Ser Ile Leu Arg Ile Leu Phe Leu Cys Glu Leu Val1 5 10 15Leu Phe Met Glu His Arg Ala Gln Met Ala Glu Gly Gly Gln Ser Ser20 25 30Ile Ala Leu Leu Ala Glu Ala Pro Thr Leu Pro Leu Ile Glu Glu Leu35 40 45Leu Glu Glu Ser Pro Gly Glu Gln Pro Arg Lys Pro Arg Leu Leu Gly50 55 60His Ser Leu Arg Tyr Met Leu Glu Leu Tyr Arg Arg Ser Ala Asp Ser65 70 75 80His Gly His Pro Arg Glu Asn Arg Thr Ile Gly Ala Thr Met Val Arg85 90 95Leu Val Lys Pro Leu Thr Ser Val Ala Arg Pro His Arg Gly Thr Trp100 105 110His Ile Gln Ile Leu Gly Phe Pro Leu Arg Pro Asn Arg Gly Leu Tyr115 120 125Gln Leu Val Arg Ala Thr Val Val Tyr Arg His His Leu Gln Leu Thr130 135 140Arg Phe Asn Leu Ser Cys His Val Glu Pro Trp Val Gln Lys Asn Pro
145 150 155 160Thr Asn His Phe Pro Ser Ser Glu Gly Asp Ser Ser Lys Pro Ser Leu165 170 175Met Ser Asn Ala Trp Lys Glu Met Asp Ile Thr Gln Leu Val Gln Gln180 185 190Arg Phe Trp Asn Asn Lys Gly His Arg Ile Leu Arg Leu Arg Phe Met195 200 205Cys Gln Gln Gln Lys Asp Ser Gly Gly Leu Glu Leu Trp His Gly Thr210 215 220Ser Ser Leu Asp Ile Ala Phe Leu Leu Leu Tyr Phe Asn Asp Thr His225 230 235 240Lys Ser Ile Arg Lys Ala Lys Phe Leu Pro Arg Gly Met Glu Glu Phe245 250 255Met Glu Arg Glu Ser Leu Leu Arg Arg Thr Arg Gln Ala Asp Gly Ile260 265 270Ser Ala Glu Val Thr Ala Ser Ser Ser Lys His Ser Gly Pro Glu Asn275 280 285Asn Gln Cys Ser Leu His Pro Phe Gln Ile Ser Phe Arg Gln Leu Gly290 295 300Trp Asp His Trp Ile Ile Ala Pro Pro Phe Tyr Thr Pro Asn Tyr Cys305 310 315 320Lys Gly Thr Cys Leu Arg Val Leu Arg Asp Gly Leu Asn Ser Pro Asn325 330 335His Ala Ile Ile Gln Asn Leu Ile Asn Gln Leu Val Asp Gln Ser Val340 345 350Pro Arg Pro Ser Cys Val Pro Tyr Lys Tyr Val Pro Ile Ser Val Leu355 360 365Met Ile Glu Ala Asn Gly Ser Ile Leu Tyr Lys Glu Tyr Glu Gly Met370 375 380Ile Ala Glu Ser Cys Thr Cys Arg385 390<210>41<211>375<212>DNA<213>智人(Homo sapiens)
<400>41caagcagatg gtatctcagc tgaggttact gcctcttcct caaaacatag cgggcctgaa 60aataaccagt gttccctcca ccctttccaa atcagcttcc gccagctggg ttgggatcac 120tggatcattg ctcccccttt ctacacccca aactactgta aaggaacttg tctccgagta 180ctacgcgatg gtctcaattc ccccaatcac gccattattc agaaccttat caatcagttg 240gtggaccaga gtgtcccccg gccctcctgt gtcccgtata agtatgttcc aattagtgtc 300cttatgattg aggcaaatgg gagtattttg tacaaggagt atgagggtat gattgctgag 360tcttgtacat gcaga 375<210>42<211>125<212>PRT<213>智人(Homo sapiens)<400>42Gln Ala Asp Gly Ile Ser Ala Glu Val Thr Ala Ser Ser Ser Lys His1 5 10 15Ser Gly Pro Glu Asn Asn Gln Cys Ser Leu His Pro Phe Gln Ile Ser20 25 30Phe Arg Gln Leu Gly Trp Asp His Trp Ile Ile Ala Pro Pro Phe Tyr35 40 45Thr Pro Asn Tyr Cys Lys Gly Thr Cys Leu Arg Val Leu Arg Asp Gly50 55 60Leu Asn Ser Pro Asn His Ala Ile Ile Gln Asn Leu Ile Asn Gln Leu65 70 75 80Val Asp Gln Ser Val Pro Arg Pro Ser Cys Val Pro Tyr Lys Tyr Val85 90 95Pro Ile Ser Val Leu Met Ile Glu Ala Asn Gly Ser Ile Leu Tyr Lys100 105 110Glu Tyr Glu Gly Met Ile Ala Glu Ser Cys Thr Cys Arg115 120 125<210>43<211>1744<212>DNA<213>智人(Homo sapiens)<400>43atgcacgccc actgcctgcc cttccttctg cacgcctggt gggccctact ccaggcgggt60gctgcgacgg tggccactgc gctcctgcgt acgcgggggc agccctcgtc gccatcccct 120ctggcgtaca tgctgagcct ctaccgcgac ccgctgccga gggcagacat catccgcagc 180ctacaggcag aagatgtggc agtggatggg cagaactgga cgtttgcttt tgacttctcc 240ttcctgagcc aacaagagga tctggcatgg gctgagctcc ggctgcagct gtccagccct 300gtggacctcc ccactgaggg ctcacttgcc attgagattt tccaccagcc aaagcccgac 360acagagcagg cttcagacag ctgcttagag cggtttcaga tggacctatt cactgtcact 420
ttgtcccagg tcaccttttc cttgggcagc atggttttgg aggtgaccag gcctctctcc480aagtggctga agcgccctgg ggccctggag aagcagatgt ccagggtagc tggagagtgc540tggccgcggc cccccacacc gcctgccacc aatgtgctcc ttatgctcta ctccaacctc600tcgcaggagc agaggcagct gggtgggtcc accttgctgt gggaagccga gagctcctgg660cgggcccagg agggacagct gtcctgggag tggggcaaga ggcaccgtcg acatcacttg720ccagacagaa gtcaactgtg tcggaaggtc aagttccagg tggacttcaa cctgatcgga780tggggctcct ggatcatcta ccccaagcag tacaacgcct atcgctgtga gggcgagtgt840cctaatcctg ttggggagga gtttcatccg accaaccatg catacatcca gagtctgctg900aaacgttacc agccccaccg agtcccttcc acttgttgtg ccccagtgaa gaccaagccg960c tgagcatgc tgtatgtgga taatggcaga gtgctcctag atcaccataa agacatgatc 1020gtggaagaat gtgggtgcct ctgatgacat cctggaggga gactggattt gcctgcactc 1080tggaaggctg ggaaactcct ggaagacatg ataaccatct aatccagtaa ggagaaacag 1140agaggggcaa agttgctctg cccaccagaa ctgaagagga ggggctgccc actctgtaaa 1200tgaagggctc agtggagtct ggccaagcac agaggctgct gtcaggaaga gggaggaaga 1260agcctgtgca gggggctggc tggatgttct ctttactgaa aagacagtgg caaggaaaag 1320cacaagtgca tgagttcttt actggatttt ttaaaaacct gtgaaccccc cgaaactgta 1380tgtgaaagtt gagacatatg tgcatgtatt ttggaggtgg gatgaagtca cctatagctt 1440tcatgtattc tccaaagtag tctgtgtgtg acctgtcccc ctccccaaag attaaggatc 1500actgtataga ttaaaaagag tccgtcaatc tcattgcctc aggctgggtt gggggagccc 1560cacagctttc tggctggcca gtggcaatct actggccttg tccagaggct cactggagtg 1620gttctctgct aatgagctgt acaacaataa agccattgtc tagttaaaaa aaaaaaaaaa 1680aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1740aaaa1744<210>44<211>347<212>PRT<213>智人(Homo sapiens)<400>44Met His Ala His Cys Leu Pro Phe Leu Leu His Ala Trp Trp Ala Leu1 5 10 15Leu Gln Ala Gly Ala Ala Thr Val Ala Thr Ala Leu Leu Arg Thr Arg20 25 30Gly Gln Pro Ser Ser Pro Ser Pro Leu Ala Tyr Met Leu Ser Leu Tyr35 40 45Arg Asp Pro Leu Pro Arg Ala Asp Ile Ile Arg Ser Leu Gln Ala Glu50 55 60Asp Val Ala Val Asp Gly Gln Asn Trp Thr Phe Ala Phe Asp Phe Ser65 70 75 80Phe Leu Ser Gln Gln Glu Asp Leu Ala Trp Ala Glu Leu Arg Leu Gln85 90 95Leu Ser Ser Pro Val Asp Leu Pro Thr Glu Gly Ser Leu Ala Ile Glu100 105 110Ile Phe His Gln Pro Lys Pro Asp Thr Glu Gln Ala Ser Asp Ser Cys
115 120 125Leu Glu Arg Phe Gln Met Asp Leu Phe Thr Val Thr Leu Ser Gln Val130 135 140Thr Phe Ser Leu Gly Ser Met Val Leu Glu Val Thr Arg Pro Leu Ser145 150 155 160Lys Trp Leu Lys Arg Pro Gly Ala Leu Glu Lys Gln Met Ser Arg Val165 170 175Ala Gly Glu Cys Trp Pro Arg Pro Pro Thr Pro Pro Ala Thr Asn Val180 185 190Leu Leu Met Leu Tyr Ser Asn Leu Ser Gln Glu Gln Arg Gln Leu Gly195 200 205Gly Ser Thr Leu Leu Trp Glu Ala Glu Ser Ser Trp Arg Ala Gln Glu210 215 220Gly Gln Leu Ser Trp Glu Trp Gly Lys Arg His Arg Arg His His Leu225 230 235 240Pro Asp Arg Ser Gln Leu Cys Arg Lys Val Lys Phe Gln Val Asp Phe245 250 255Asn Leu Ile Gly Trp Gly Ser Trp Ile Ile Tyr Pro Lys Gln Tyr Asn260 265 270Ala Tyr Arg Cys Glu Gly Glu Cys Pro Asn Pro Val Gly Glu Glu Phe275 280 285His Pro Thr Asn His Ala Tyr Ile Gln Ser Leu Leu Lys Arg Tyr Gln290 295 300Pro His Arg Val Pro Ser Thr Cys Cys Ala Pro Val Lys Thr Lys Pro305 310 315 320Leu Ser Met Leu Tyr Val Asp Asn Gly Arg Val Leu Leu Asp His His325 330 335Lys Asp Met Ile Val Glu Glu Cys Gly Cys Leu340 345<210>45<211>504<212>DNA<213>智人(Homo sapiens)<400>45tggccgcggc cccccacacc gcctgccacc aatgtgctcc ttatgctcta ctccaacctc 60tcgcaggagc agaggcagct gggtgggtcc accttgctgt gggaagccga gagctcctgg120
cgggcccagg agggacagct gtcctgggag tggggcaaga ggcaccgtcg acatcacttg180ccagacagaa gtcaactgtg tcggaaggtc aagttccagg tggacttcaa cctgatcgga240tggggctcct ggatcatcta ccccaagcag tacaacgcct atcgctgtga gggcgagtgt300cctaatcctg ttggggagga gtttcatccg accaaccatg catacatcca gagtctgctg360aaacgttacc agccccaccg agtcccttcc acttgttgtg ccccagtgaa gaccaagccg420ctgagcatgc tgtatgtgga taatggcaga gtgctcctag atcaccataa agacatgatc480gtggaagaat gtgggtgcct ctga 504<210>46<211>167<212>PRT<213>智人(Homo sapiens)<400>46Trp Pro Arg Pro Pro Thr Pro Pro Ala Thr Asn Val Leu Leu Met Leu1 5 10 15Tyr Ser Asn Leu Ser Gln Glu Gln Arg Gln Leu Gly Gly Ser Thr Leu20 25 30Leu Trp Glu Ala Glu Ser Ser Trp Arg Ala Gln Glu Gly Gln Leu Ser35 40 45Trp Glu Trp Gly Lys Arg His Arg Arg His His Leu Pro Asp Arg Ser50 55 60Gln Leu Cys Arg Lys Val Lys Phe Gln Val Asp Phe Asn Leu Ile Gly65 70 75 80Trp Gly Ser Trp Ile Ile Tyr Pro Lys Gln Tyr Asn Ala Tyr Arg Cys85 90 95Glu Gly Glu Cys Pro Asn Pro Val Gly Glu Glu Phe His Pro Thr Asn100 105 110His Ala Tyr Ile Gln Ser Leu Leu Lys Arg Tyr Gln Pro His Arg Val115 120 125Pro Ser Thr Cys Cys Ala Pro Val Lys Thr Lys Pro Leu Ser Met Leu130 135 140Tyr Val Asp Asn Gly Arg Val Leu Leu Asp His His Lys Asp Met Ile145 150 155 160Val Glu Glu Cys Gly Cys Leu165<210>47<211>1101<212>DNA<213>智人(Homo sapiens)
<400>47atgcagcccc tgtggctctg ctgggcactc tgggtgttgc ccctggccag ccccggggcc60gccctgaccg gggagcagct cctgggcagc ctgctgcggc agctgcagct caaagaggtg 120cccaccctgg acagggccga catggaggag ctggtcatcc ccacccacgt gagggcccag 180tacgtggccc tgctgcagcg cagccacggg gaccgctccc gcggaaagag gttcagccag 240agcttccgag aggtggccgg caggttcctg gcgttggagg ccagcacaca cctgctggtg 300ttcggcatgg agcagcggct gccgcccaac agcgagctgg tgcaggccgt gctgcggctc 360ttccaggagc cggtccccaa ggccgcgctg cacaggcacg ggcggctgtc cccgcgcagc 420gcccgggccc gggtgaccgt cgagtggctg cgcgtccgcg acgacggctc caaccgcacc 480tccctcatcg actccaggct ggtgtccgtc cacgagagcg gctggaaggc cttcgacgtg 540accgaggccg tgaacttctg gcagcagctg agccggcccc ggcagccgct gctgctacag 600gtgtcggtgc agagggagca tctgggcccg ctggcgtccg gcgcccacaa gctggtccgc 660tttgcctcgc agggggcgcc agccgggctt ggggagcccc agctggagct gcacaccctg 720gaccttgggg actatggagc tcagggcgac tgtgaccctg aagcaccaat gaccgagggc 780acccgctgct gccgccagga gatgtacatt gacctgcagg ggatgaagtg ggccgagaac 840tgggtgctgg agcccccggg cttcctggct tatgagtgtg tgggcacctg ccggcagccc 900ccggaggccc tggccttcaa gtggccgttt ctggggcctc gacagtgcat cgcctcggag 960actgcctcgc tgcccatgat cgtcagcatc aaggagggag gcaggaccag gccccaggtg 1020gtcagcctgc ccaacatgag ggtgcagaag tgcagctgtg cctcggatgg tgcgctcgtg 1080ccaaggaggc tccagccata g1101<210>48<211>366<212>PRT<213>智人(Homo sapiens)<400>48Met Gln Pro Leu Trp Leu Cys Trp Ala Leu Trp Val Leu Pro Leu Ala1 5 10 15Ser Pro Gly Ala Ala Leu Thr Gly Glu Gln Leu Leu Gly Ser Leu Leu20 25 30Arg Gln Leu Gln Leu Lys Glu Val Pro Thr Leu Asp Arg Ala Asp Met35 40 45Glu Glu Leu Val Ile Pro Thr His Val Arg Ala Gln Tyr Val Ala Leu50 55 60Leu Gln Arg Ser His Gly Asp Arg Ser Arg Gly Lys Arg Phe Ser Gln65 70 75 80Ser Phe Arg Glu Val Ala Gly Arg Phe Leu Ala Leu Glu Ala Ser Thr85 90 95His Leu Leu Val Phe Gly Met Glu Gln Arg Leu Pro Pro Asn Ser Glu100 105 110Leu Val Gln Ala Val Leu Arg Leu Phe Gln Glu Pro Val Pro Lys Ala115 120 125Ala Leu His Arg His Gly Arg Leu Ser Pro Arg Ser Ala Arg Ala Arg
130 135 140Val Thr Val Glu Trp Leu Arg Val Arg Asp Asp Gly Ser Asn Arg Thr145 150 155 160Ser Leu Ile Asp Ser Arg Leu Val Ser Val His Glu Ser Gly Trp Lys165 170 175Ala Phe Asp Val Thr Glu Ala Val Asn Phe Trp Gln Gln Leu Ser Arg180 185 190Pro Arg Gln Pro Leu Leu Leu Gln Val Ser Val Gln Arg Glu His Leu195 200 205Gly Pro Leu Ala Ser Gly Ala His Lys Leu Val Arg Phe Ala Ser Gln210 215 220Gly Ala Pro Ala Gly Leu Gly Glu Pro Gln Leu Glu Leu His Thr Leu225 230 235 240Asp Leu Gly Asp Tyr Gly Ala Gln Gly Asp Cys Asp Pro Glu Ala Pro245 250 255Met Thr Glu Gly Thr Arg Cys Cys Arg Gln Glu Met Tyr Ile Asp Leu260 265 270Gln Gly Met Lys Trp Ala Glu Asn Trp Val Leu Glu Pro Pro Gly Phe275 280 285Leu Ala Tyr Glu Cys Val Gly Thr Cys Arg Gln Pro Pro Glu Ala Leu290 295 300Ala Phe Lys Trp Pro Phe Leu Gly Pro Arg Gln Cys Ile Ala Ser Glu305 310 315 320Thr Ala Ser Leu Pro Met Ile Val Ser Ile Lys Glu Gly Gly Arg Thr325 330 335Arg Pro Gln Val Val Ser Leu Pro Asn Met Arg Val Gln Lys Cys Ser340 345 350Cys Ala Ser Asp Gly Ala Leu Val Pro Arg Arg Leu Gln Pro355 360 365<210>49<211>1098<212>DNA<213>智人(Homo sapiens)<400>49atgtggcccc tgtggctctg ctgggcactc tgggtgctgc ccctggctgg ccccggggcg60gccctgaccg aggagcagct cctgggcagc ctgctgcggc agctgcagct cagcgaggtg 120
cccgtactgg acagggccga catggagaag ctggtcatcc ccgcccacgt gagggcccag180tatgtagtcc tgctgcggcg cagccacggg gaccgctccc gcggaaagag gttcagccag240agcttccgag aggtggccgg caggttcctg gcgtcggagg ccagcacaca cctgctggtg300ttcggcatgg agcagcggct gccgcccaac agcgagctgg tgcaggccgt gctgcggctc360ttccaggagc cggtccccaa ggccgcgctg cacaggcacg ggcggctgtc cccgcgcagc420gcccaggccc gggtgaccgt cgagtggctg cgcgtccgcg acgacggctc caaccgcacc480tccctcatcg actccaggct ggtgtccgtc cacgagagcg gctggaaggc cttcgacgtg540accgaggccg tgaacttctg gcagcagctg agccggcccc ggcagccgct gctgctacag600gtgtcggtgc agagggagca tctgggcccg ctggcgtccg gcgcccacaa gctggtccgc660tttgcctcgc agggggcgcc agccgggctt ggggagcccc agctggagct gcacaccctg720gacctcaggg actatggagc tcagggcgac tgtgaccctg aagcaccaat gaccgagggc780acccgctgct gccgccagga gatgtacatt gacctgcagg ggatgaagtg ggccaagaac840tgggtgctgg agcccccggg cttcctggct tacgagtgtg tgggcacctg ccagcagccc900ccggaggccc tggccttcaa ttggccattt ctggggccgc gacagtgtat cgcctcggag960actgcctcgc tgcccatgat cgtcagcatc aaggagggag gcaggaggcc ccaggtggtc 1020agcctgccca acatgagggt gcagaagtgc agctgtgcct cggatggggc gctcgtgcca 1080aggaggctcc agccatag 1098<210>50<211>365<212>PRT<213>智人(Homo sapiens)<400>50Met Trp Pro Leu Trp Leu Cys Trp Ala Leu Trp Val Leu Pro Leu Ala1 5 10 15Gly Pro Gly Ala Ala Leu Thr Glu Glu Gln Leu Leu Gly Ser Leu Leu20 25 30Arg Gln Leu Gln Leu Ser Glu Val Pro Val Leu Asp Arg Ala Asp Met35 40 45Glu Lys Leu Val Ile Pro Ala His Val Arg Ala Gln Tyr Val Val Leu50 55 60Leu Arg Arg Ser His Gly Asp Arg Ser Arg Gly Lys Arg Phe Ser Gln65 70 75 80Ser Phe Arg Glu Val Ala Gly Arg Phe Leu Ala Ser Glu Ala Ser Thr85 90 95His Leu Leu Val Phe Gly Met Glu Gln Arg Leu Pro Pro Asn Ser Glu100 105 110Leu Val Gln Ala Val Leu Arg Leu Phe Gln Glu Pro Val Pro Lys Ala115 120 125Ala Leu His Arg His Gly Arg Leu Ser Pro Arg Ser Ala Gln Ala Arg130 135 140Val Thr Val Glu Trp Leu Arg Val Arg Asp Asp Gly Ser Asn Arg Thr
145 150 155 160Ser Leu Ile Asp Ser Arg Leu Val Ser Val His Glu Ser Gly Trp Lys165 170 175Ala Phe Asp Val Thr Glu Ala Val Asn Phe Trp Gln Gln Leu Ser Arg180 185 190Pro Arg Gln Pro Leu Leu Leu Gln Val Ser Val Gln Arg Glu His Leu195 200 205Gly Pro Leu Ala Ser Gly Ala His Lys Leu Val Arg Phe Ala Ser Gln210 215 220Gly Ala Pro Ala Gly Leu Gly Glu Pro Gln Leu Glu Leu His Thr Leu225 230 235 240Asp Leu Arg Asp Tyr Gly Ala Gln Gly Asp Cys Asp Pro Glu Ala Pro245 250 255Met Thr Glu Gly Thr Arg Cys Cys Arg Gln Glu Met Tyr Ile Asp Leu260 265 270Gln Gly Met Lys Trp Ala Lys Asn Trp Val Leu Glu Pro Pro Gly Phe275 280 285Leu Ala Tyr Glu Cys Val Gly Thr Cys Gln Gln Pro Pro Glu Ala Leu290 295 300Ala Phe Asn Trp Pro Phe Leu Gly Pro Arg Gln Cys Ile Ala Ser Glu305 310 315 320Thr Ala Ser Leu Pro Met Ile Val Ser Ile Lys Glu Gly Gly Arg Arg325 330 335Pro Gln Val Val Ser Leu Pro Asn Met Arg Val Gln Lys Cys Ser Cys340 345 350Ala Ser Asp Gly Ala Leu Val Pro Arg Arg Leu Gln Pro355 360 365<210>51<211>2291<212>DNA<213>智人(Homo sapiens)<400>51ctttccgccc cagccctgaa agcgttaacc ctggagcttt ctgcacaccc cccgaccgct 60cccgcccaag cttcctaaaa aagaaaggtg caaagtttgg tccaggatag aaaaatgact120gatcaaaggc aggcgatact tcctgttgcc gggacgctat atataacgtg atgagcgcac180gggctgcgga gacgcaccgg agcgctcgcc cagccgccgc ctccaagccc ctgaggtttc240cggggaccac aatgaacaag ttgctgtgct gcgcgctcgt gtttctggac atctccatta300
agtggaccac ccaggaaacg tttcctccaa agtaccttca ttatgacgaa gaaacctctc360atcagctgtt gtgtgacaaa tgtcctcctg gtacctacct aaaacaacac tgtacagcaa420agtggaagac cgtgtgcgcc ccttgccctg accactacta cacagacagc tggcacacca480gtgacgagtg tctatactgc agccccgtgt gcaaggagct gcagtacgtc aagcaggagt540gcaatcgcac ccacaaccgc gtgtgcgaat gcaaggaagg gcgctacctt gagatagagt600tctgcttgaa acataggagc tgccctcctg gatttggagt ggtgcaagct ggaaccccag660agcgaaatac agtttgcaaa agatgtccag atgggttctt ctcaaatgag acgtcatcta720aagcaccctg tagaaaacac acaaattgca gtgtctttgg tctcctgcta actcagaaag780gaaatgcaac acacgacaac atatgttccg gaaacagtga atcaactcaa aaatgtggaa840tagatgttac cctgtgtgag gaggcattct tcaggtttgc tgttcctaca aagtttacgc900ctaactggct tagtgtcttg gtagacaatt tgcctggcac caaagtaaac gcagagagtg960tagagaggat aaaacggcaa cacagctcac aagaacagac tttccagctg ctgaagttat 1020ggaaacatca aaacaaagac caagatatag tcaagaagat catccaagat attgacctct 1080gtgaaaacag cgtgcagcgg cacattggac atgctaacct caccttcgag cagcttcgta 1140gcttgatgga aagcttaccg ggaaagaaag tgggagcaga agacattgaa aaaacaataa 1200aggcatgcaa acccagtgac cagatcctga agctgctcag tttgtggcga ataaaaaatg 1260gcgaccaaga caccttgaag ggcctaatgc acgcactaaa gcactcaaag acgtaccact 1320ttcccaaaac tgtcactcag agtctaaaga agaccatcag gttccttcac agcttcacaa 1380tgtacaaatt gtatcagaag ttatttttag aaatgatagg taaccaggtc caatcagtaa 1440aaataagctg cttataactg gaaatggcca ttgagctgtt tcctcacaat tggcgagatc 1500ccatggatga gtaaactgtt tctcaggcac ttgaggcttt cagtgatatc tttctcatta 1560ccagtgacta attttgccac agggtactaa aagaaactat gatgtggaga aaggactaac 1620atctcctcca ataaacccca aatggttaat ccaactgtca gatctggatc gttatctact 1680gactatattt tcccttatta ctgcttgcag taattcaact ggaaattaaa aaaaaaaaac 1740tagactccat tgtgccttac taaatatggg aatgtctaac ttaaatagct ttgagatttc 1800agctatgcta gaggctttta ttagaaagcc atattttttt ctgtaaaagt tactaatata 1860tctgtaacac tattacagta ttgctattta tattcattca gatataagat ttgtacatat 1920tatcatccta taaagaaacg gtatgactta attttagaaa gaaaattata ttctgtttat 1980tatgacaaat gaaagagaaa atatatattt ttaatggaaa gtttgtagca tttttctaat 2040aggtactgcc atatttttct gtgtggagta tttttataat tttatctgta taagctgtaa 2100tatcatttta tagaaaatgc attatttagt caattgttta atgttggaaa acatatgaaa 2160tataaattat ctgaatatta gatgctctga gaaattgaat gtaccttatt taaaagattt 2220tatggtttta taactatata aatgacatta ttaaagtttt caaattattt tttaaaaaaa 2280aaaaaaaaaa a2291<210>52<211>401<212>PRT<213>智人(Homo sapiens)<400>52Met Asn Lys Leu Leu Cys Cys Ala Leu Val Phe Leu Asp Ile Ser Ile1 5 10 15Lys Trp Thr Thr Gln Glu Thr Phe Pro Pro Lys Tyr Leu His Tyr Asp20 25 30Glu Glu Thr Ser His Gln Leu Leu Cys Asp Lys Cys Pro Pro Gly Thr35 40 45Tyr Leu Lys Gln His Cys Thr Ala Lys Trp Lys Thr Val Cys Ala Pro50 55 60
Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His Thr Ser Asp Glu Cys65 70 75 80Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu Gln Tyr Val Lys Gln Glu85 90 95Cys Asn Arg Thr His Asn Arg Val Cys Glu Cys Lys Glu Gly Arg Tyr100 105 110Leu Glu Ile Glu Phe Cys Leu Lys His Arg Ser Cys Pro Pro Gly Phe115 120 125Gly Val Val Gln Ala Gly Thr Pro Glu Arg Asn Thr Val Cys Lys Arg130 135 140Cys Pro Asp Gly Phe Phe Ser Asn Glu Thr Ser Ser Lys Ala Pro Cys145 150 155 160Arg Lys His Thr Asn Cys Ser Val Phe Gly Leu Leu Leu Thr Gln Lys165 170 175Gly Asn Ala Thr His Asp Asn Ile Cys Ser Gly Asn Ser Glu Ser Thr180 185 190Gln Lys Cys Gly Ile Asp Val Thr Leu Cys Glu Glu Ala Phe Phe Arg195 200 205Phe Ala Val Pro Thr Lys Phe Thr Pro Asn Trp Leu Ser Val Leu Val210 215 220Asp Asn Leu Pro Gly Thr Lys Val Asn Ala Glu Ser Val Glu Arg Ile225 230 235 240Lys Arg Gln His Ser Ser Gln Glu Gln Thr Phe Gln Leu Leu Lys Leu245 250 255Trp Lys His Gln Asn Lys Asp Gln Asp Ile Val Lys Lys Ile Ile Gln260 265 270Asp Ile Asp Leu Cys Glu Asn Ser Val Gln Arg His Ile Gly His Ala275 280 285Asn Leu Thr Phe Glu Gln Leu Arg Ser Leu Met Glu Ser Leu Pro Gly290 295 300Lys Lys Val Gly Ala Glu Asp Ile Glu Lys Thr Ile Lys Ala Cys Lys305 310 315 320Pro Ser Asp Gln Ile Leu Lys Leu Leu Ser Leu Trp Arg Ile Lys Asn325 330 335
Gly Asp Gln Asp Thr Leu Lys Gly Leu Met His Ala Leu Lys His Ser340 345 350Lys Thr Tyr His Phe Pro Lys Thr Val Thr Gln Ser Leu Lys Lys Thr355 360 365Ile Arg Phe Leu His Ser Phe Thr Met Tyr Lys Leu Tyr Gln Lys Leu370 375 380Phe Leu Glu Met Ile Gly Asn Gln Val Gln Ser Val Lys Ile Ser Cys385 390 395 400Leu<210>53<211>1014<212>DNA<213>智人(Homo sapiens)<400>53ccttgccctg accactacta cacagacagc tggcacacca gtgacgagtg tctatactgc 60agccccgtgt gcaaggagct gcagtacgtc aagcaggagt gcaatcgcac ccacaaccgc120gtgtgcgaat gcaaggaagg gcgctacctt gagatagagt tctgcttgaa acataggagc180tgccctcctg gatttggagt ggtgcaagct ggaaccccag agcgaaatac agtttgcaaa240agatgtccag atgggttctt ctcaaatgag acgtcatcta aagcaccctg tagaaaacac300acaaattgca gtgtctttgg tctcctgcta actcagaaag gaaatgcaac acacgacaac360atatgttccg gaaacagtga atcaactcaa aaatgtggaa tagatgttac cctgtgtgag420gaggcattct tcaggtttgc tgttcctaca aagtttacgc ctaactggct tagtgtcttg480gtagacaatt tgcctggcac caaagtaaac gcagagagtg tagagaggat aaaacggcaa540cacagctcac aagaacagac tttccagctg ctgaagttat ggaaacatca aaacaaagac600caagatatag tcaagaagat catccaagat attgacctct gtgaaaacag cgtgcagcgg660cacattggac atgctaacct caccttcgag cagcttcgta gcttgatgga aagcttaccg720ggaaagaaag tgggagcaga agacattgaa aaaacaataa aggcatgcaa acccagtgac780cagatcctga agctgctcag tttgtggcga ataaaaaatg gcgaccaaga caccttgaag840ggcctaatgc acgcactaaa gcactcaaag acgtaccact ttcccaaaac tgtcactcag900agtctaaaga agaccatcag gttccttcac agcttcacaa tgtacaaatt gtatcagaag960ttatttttag aaatgatagg taaccaggtc caatcagtaa aaataagctg ctta 1014<210>54<211>338<212>PRT<213>智人(Homo sapiens)<400>54Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His Thr Ser Asp Glu1 5 10 15Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu Gln Tyr Val Lys Gln20 25 30Glu Cys Asn Arg Thr His Asn Arg Val Cys Glu Cys Lys Glu Gly Arg
35 40 45Tyr Leu Glu Ile Glu Phe Cys Leu Lys His Arg Ser Cys Pro Pro Gly50 55 60Phe Gly Val Val Gln Ala Gly Thr Pro Glu Arg Asn Thr Val Cys Lys65 70 75 80Arg Cys Pro Asp Gly Phe Phe Ser Asn Glu Thr Ser Ser Lys Ala Pro85 90 95Cys Arg Lys His Thr Asn Cys Ser Val Phe Gly Leu Leu Leu Thr Gln100 105 110Lys Gly Asn Ala Thr His Asp Asn Ile Cys Ser Gly Asn Ser Glu Ser115 120 125Thr Gln Lys Cys Gly Ile Asp Val Thr Leu Cys Glu Glu Ala Phe Phe130 135 140Arg Phe Ala Val Pro Thr Lys Phe Thr Pro Asn Trp Leu Ser Val Leu145 150 155 160Val Asp Asn Leu Pro Gly Thr Lys Val Asn Ala Glu Ser Val Glu Arg165 170 175Ile Lys Arg Gln His Ser Ser Gln Glu Gln Thr Phe Gln Leu Leu Lys180 185 190Leu Trp Lys His Gln Asn Lys Asp Gln Asp Ile Val Lys Lys Ile Ile195 200 205Gln Asp Ile Asp Leu Cys Glu Asn Ser Val Gln Arg His Ile Gly His210 215 220Ala Asn Leu Thr Phe Glu Gln Leu Arg Ser Leu Met Glu Ser Leu Pro225 230 235 240Gly Lys Lys Val Gly Ala Glu Asp Ile Glu Lys Thr Ile Lys Ala Cys245 250 255Lys Pro Ser Asp Gln Ile Leu Lys Leu Leu Ser Leu Trp Arg Ile Lys260 265 270Asn Gly Asp Gln Asp Thr Leu Lys Gly Leu Met His Ala Leu Lys His275 280 285Ser Lys Thr Tyr His Phe Pro Lys Thr Val Thr Gln Ser Leu Lys Lys290 295 300Thr Ile Arg Phe Leu His Ser Phe Thr Met Tyr Lys Leu Tyr Gln Lys305 310 315 320
Leu Phe Leu Glu Met Ile Gly Asn Gln Val Gln Ser Val Lys Ile Ser325 330 335Cys Leu<210>55<211>2312<212>DNA<213>智人(Homo sapiens)<400>55tccagtgacg gagccgcccg gccgacagcc ccgagacgac agcccggcgc gtcccggtcc 60ccacctccga ccaccgccag cgctccaggc cccgcgctcc ccgctcgccg ccaccgcgcc120ctccgctccg cccgcagtgc caaccatgac cgccgccagt atgggccccg tccgcgtcgc180cttcgtggtc ctcctcgccc tctgcagccg gccggccgtc ggccagaact gcagcgggcc240gtgccggtgc ccggacgagc cggcgccgcg ctgcccggcg ggcgtgagcc tcgtgctgga300cggctgcggc tgctgccgcg tctgcgccaa gcagctgggc gagctgtgca ccgagcgcga360cccctgcgac ccgcacaagg gcctcttctg tgacttcggc tccccggcca accgcaagat420cggcgtgtgc accgccaaag atggtgctcc ctgcatcttc ggtggtacgg tgtaccgcag480cggagagtcc ttccagagca gctgcaagta ccagtgcacg tgcctggacg gggcggtggg540ctgcatgccc ctgtgcagca tggacgttcg tctgcccagc cctgactgcc ccttcccgag600gagggtcaag ctgcccggga aatgctgcga ggagtgggtg tgtgacgagc ccaaggacca660aaccgtggtt gggcctgccc tcgcggctta ccgactggaa gacacgtttg gcccagaccc720aactatgatt agagccaact gcctggtcca gaccacagag tggagcgcct gttccaagac780ctgtgggatg ggcatctcca cccgggttac caatgacaac gcctcctgca ggctagagaa840gcagagccgc ctgtgcatgg tcaggccttg cgaagctgac ctggaagaga acattaagaa900gggcaaaaag tgcatccgta ctcccaaaat ctccaagcct atcaagtttg agctttctgg960ctgcaccagc atgaagacat accgagctaa attctgtgga gtatgtaccg acggccgatg 1020ctgcaccccc cacagaacca ccaccctgcc ggtggagttc aagtgccctg acggcgaggt 1080catgaagaag aacatgatgt tcatcaagac ctgtgcctgc cattacaact gtcccggaga 1140caatgacatc tttgaatcgc tgtactacag gaagatgtac ggagacatgg catgaagcca 1200gagagtgaga gacattaact cattagactg gaacttgaac tgattcacat ctcatttttc 1260cgtaaaaatg atttcagtag cacaagttat ttaaatctgt ttttctaact gggggaaaag 1320attcccaccc aattcaaaac attgtgccat gtcaaacaaa tagtctatct tccccagaca 1380ctggtttgaa gaatgttaag acttgacagt ggaactacat tagtacacag caccagaatg 1440tatattaagg tgtggcttta ggagcagtgg gagggtacca gcagaaaggt tagtatcatc 1500agatagctct tatacgagta atatgcctgc tatttgaagt gtaattgaga aggaaaattt 1560tagcgtgctc actgacctgc ctgtagcccc agtgacagct aggatgtgca ttctccagcc 1620atcaagagac tgagtcaagt tgttccttaa gtcagaacag cagactcagc tctgacattc 1680tgattcgaat gacactgttc aggaatcgga atcctgtcga ttagactgga cagcttgtgg 1740caagtgaatt tcctgtaaca agccagattt tttaaaattt atattgtaaa tattgtgtgt 1800gtgtgtgtgt gtgtatatat atatatatat gtacagttat ctaagttaat ttaaagttgt 1860ttgtgccttt ttatttttgt ttttaatgct ttgatatttc aatgttagcc tcaatttctg 1920aacaccatag gtagaatgta aagcttgtct gatcgttcaa agcatgaaat ggatacttat 1980atggaaattc tctcagatag aatgacagtc cgtcaaaaca gattgtttgc aaaggggagg 2040catcagtgtc cttggcaggc tgatttctag gtaggaaatg tggtagctca cgctcacttt 2100taatgaacaa atggccttta ttaaaaactg agtgactcta tatagctgat cagttttttc 2160acctggaagc atttgtttct actttgatat gactgttttt cggacagttt atttgttgag 2220agtgtgacca aaagttacat gtttgcacct ttctagttga aaataaagta tattttttct 2280aaaaaaaaaa aaaaacgaca gcaacggaat tc 2312
<210>56<211>349<212>PRT<213>智人(Homo sapiens)<400>56Met Thr Ala Ala Ser Met Gly Pro Val Arg Val Ala Phe Val Val Leu1 5 10 15Leu Ala Leu Cys Ser Arg Pro Ala Val Gly Gln Asn Cys Ser Gly Pro20 25 30Cys Arg Cys Pro Asp Glu Pro Ala Pro Arg Cys Pro Ala Gly Val Ser35 40 45Leu Val Leu Asp Gly Cys Gly Cys Cys Arg Val Cys Ala Lys Gln Leu50 55 60Gly Glu Leu Cys Thr Glu Arg Asp Pro Cys Asp Pro His Lys Gly Leu65 70 75 80Phe Cys Asp Phe Gly Ser Pro Ala Asn Arg Lys Ile Gly Val Cys Thr85 90 95Ala Lys Asp Gly Ala Pro Cys Ile Phe Gly Gly Thr Val Tyr Arg Ser100 105 110Gly Glu Ser Phe Gln Ser Ser Cys Lys Tyr Gln Cys Thr Cys Leu Asp115 120 125Gly Ala Val Gly Cys Met Pro Leu Cys Ser Met Asp Val Arg Leu Pro130 135 140Ser Pro Asp Cys Pro Phe Pro Arg Arg Val Lys Leu Pro Gly Lys Cys145 150 155 160Cys Glu Glu Trp Val Cys Asp Glu Pro Lys Asp Gln Thr Val Val Gly165 170 175Pro Ala Leu Ala Ala Tyr Arg Leu Glu Asp Thr Phe Gly Pro Asp Pro180 185 190Thr Met Ile Arg Ala Asn Cys Leu Val Gln Thr Thr Glu Trp Ser Ala195 200 205Cys Ser Lys Thr Cys Gly Met Gly Ile Ser Thr Arg Val Thr Asn Asp210 215 220Asn Ala Ser Cys Arg Leu Glu Lys Gln Ser Arg Leu Cys Met Val Arg225 230 235 240
Pro Cys Glu Ala Asp Leu Glu Glu Asn Ile Lys Lys Gly Lys Lys Cys245 250 255Ile Arg Thr Pro Lys Ile Ser Lys Pro Ile Lys Phe Glu Leu Ser Gly260 265 270Cys Thr Ser Met Lys Thr Tyr Arg Ala Lys Phe Cys Gly Val Cys Thr275 280 285Asp Gly Arg Cys Cys Thr Pro His Arg Thr Thr Thr Leu Pro Val Glu290 295 300Phe Lys Cys Pro Asp Gly Glu Val Met Lys Lys Asn Met Met Phe Ile305 310 315 320Lys Thr Cys Ala Cys His Tyr Asn Cys Pro Gly Asp Asn Asp Ile Phe325 330 335Glu Ser Leu Tyr Tyr Arg Lys Met Tyr Gly Asp Met Ala340 345<210>57<211>1069<212>DNA<213>智人(Homo sapiens)<400>57cagaactgca gcgggccgtg ccggtgcccg gacgagccgg cgccgcgctg cccggcgggc60gtgagcctcg tgctggacgg ctgcggctgc tgccgcgtct gcgccaagca gctgggcgag 120ctgtgcaccg agcgcgaccc ctgcgacccg cacaagggcc tcttctgtga cttcggctcc 180ccggccaacc gcaagatcgg cgtgtgcacc gccaaagatg gtgctccctg catcttcggt 240ggtacggtgt accgcagcgg agagtccttc cagagcagct gcaagtacca gtgcacgtgc 300ctggacgggg cggtgggctg catgcccctg tgcagcatgg acgttcgtct gcccagccct 360gactgcccct tcccgaggag ggtcaagctg cccgggaaat gctgcgagga gtgggtgtgt 420gacgagccca aggaccaaac cgtggttggg cctgccctcg cggcttaccg actggaagac 480acgtttggcc cagacccaac tatgattaga gccaactgcc tggtccagac cacagagtgg 540agcgcctgtt ccaagacctg tgggatgggc atctccaccc gggttaccaa tgacaacgcc 600tcctgcaggc tagagaagca gagccgcctg tgcatggtca ggccttgcga agctgacctg 660gaagagaaca ttaagaaggg caaaaagtgc atccgtactc ccaaaatctc caagcctatc 720aagtttgagc tttctggctg caccagcatg aagacatacc gagctaaatt ctgtggagta 780tgtaccgacg gccgatgctg caccccccac agaaccacca ccctgccggt ggagttcaag 840tgccctgacg gcgaggtcat gaagaagaac atgatgttca tcaagacctg tgcctgccat 900tacaactgtc ccggagacaa tgacatcttt gaatcgctgt actacaggaa gatgtacgga 960gacatggcat gaagccagag agtgagagac attaactcat tagactggaa cttgaactga 1020ttcacatctc atttttccgt aaaaatgatt tcagtagcac aagttattt 1069<210>58<211>323<212>PRT<213>智人(Homo sapiens)<400>58
Gln Asn Cys Ser Gly Pro Cys Arg Cys Pro Asp Glu Pro Ala Pro Arg1 5 10 15Cys Pro Ala Gly Val Ser Leu Val Leu Asp Gly Cys Gly Cys Cys Arg20 25 30Val Cys Ala Lys Gln Leu Gly Glu Leu Cys Thr Glu Arg Asp Pro Cys35 40 45Asp Pro His Lys Gly Leu Phe Cys Asp Phe Gly Ser Pro Ala Asn Arg50 55 60Lys Ile Gly Val Cys Thr Ala Lys Asp Gly Ala Pro Cys Ile Phe Gly65 70 75 80Gly Thr Val Tyr Arg Ser Gly Glu Ser Phe Gln Ser Ser Cys Lys Tyr85 90 95Gln Cys Thr Cys Leu Asp Gly Ala Val Gly Cys Met Pro Leu Cys Ser100 105 110Met Asp Val Arg Leu Pro Ser Pro Asp Cys Pro Phe Pro Arg Arg Val115 120 125Lys Leu Pro Gly Lys Cys Cys Glu Glu Trp Val Cys Asp Glu Pro Lys130 135 140Asp Gln Thr Val Val Gly Pro Ala Leu Ala Ala Tyr Arg Leu Glu Asp145 150 155 160Thr Phe Gly Pro Asp Pro Thr Met Ile Arg Ala Asn Cys Leu Val Gln165 170 175Thr Thr Glu Trp Ser Ala Cys Ser Lys Thr Cys Gly Met Gly Ile Ser180 185 190Thr Arg Val Thr Asn Asp Asn Ala Ser Cys Arg Leu Glu Lys Gln Ser195 200 205Arg Leu Cys Met Val Arg Pro Cys Glu Ala Asp Leu Glu Glu Asn Ile210 215 220Lys Lys Gly Lys Lys Cys Ile Arg Thr Pro Lys Ile Ser Lys Pro Ile225 230 235 240Lys Phe Glu Leu Ser Gly Cys Thr Ser Met Lys Thr Tyr Arg Ala Lys245 250 255Phe Cys Gly Val Cys Thr Asp Gly Arg Cys Cys Thr Pro His Arg Thr260 265 270Thr Thr Leu Pro Val Glu Phe Lys Cys Pro Asp Gly Glu Val Met Lys
275 280 285Lys Asn Met Met Phe Ile Lys Thr Cys Ala Cys His Tyr Asn Cys Pro290 295 300Gly Asp Asn Asp Ile Phe Glu Ser Leu Tyr Tyr Arg Lys Met Tyr Gly305 310 315 320Asp Met Ala<210>59<211>1985<212>DNA<213>智人(Homo sapiens)<400>59gagcgaaaga cgcccgcccg ccgcccagcc ctcgcctccc tgcccaccgg gcccaccgcg 60ccgccacccc gaccccgctg cgcacggcct gtccgctgca caccagcttg ttggcgtctt120cgtcgccgcg ctcgccccgg gctactcctg cgcgccacaa tgagctcccg catcgccagg180gcgctcgcct tagtcgtcac ccttctccac ttgaccaggc tggcgctctc cacctgcccc240gctgcctgcc actgccccct ggaggcgccc aagtgcgcgc cgggagtcgg gctggtccgg300gacggctgcg gctgctgtaa ggtctgcgcc aagcagctca acgaggactg cagcaaaacg360cagccctgcg accacaccaa ggggctggaa tgcaacttcg gcgccagctc caccgctctg420aaggggatct gcagagctca gtcagagggc agaccctgtg aatataactc cagaatctac480caaaacgggg aaagtttcca gcccaactgt aaacatcagt gcacatgtat tgatggcgcc540gtgggctgca ttcctctgtg tccccaagaa ctatctctcc ccaacttggg ctgtcccaac600cctcggctgg tcaaagttac cgggcagtgc tgcgaggagt gggtctgtga cgaggatagt660atcaaggacc ccatggagga ccaggacggc ctccttggca aggagctggg attcgatgcc720tccgaggtgg agttgacgag aaacaatgaa ttgattgcag ttggaaaagg cagctcactg780aagcggctcc ctgtttttgg aatggagcct cgcatcctat acaacccttt acaaggccag840aaatgtattg ttcaaacaac ttcatggtcc cagtgctcaa agacctgtgg aactggtatc900tccacacgag ttaccaatga caaccctgag tgccgccttg tgaaagaaac ccggatttgt960gaggtgcggc cttgtggaca gccagtgtac agcagcctga aaaagggcaa gaaatgcagc 1020aagaccaaga aatcccccga accagtcagg tttacttacg ctggatgttt gagtgtgaag 1080aaataccggc ccaagtactg cggttcctgc gtggacggcc gatgctgcac gccccagctg 1140accaggactg tgaagatgcg gttccgctgc gaagatgggg agacattttc caagaacgtc 1200atgatgatcc agtcctgcaa atgcaactac aactgcccgc atgccaatga agcagcgttt 1260cccttctaca ggctgttcaa tgacattcac aaatttaggg actaaatgct acctgggttt 1320ccagggcaca cctagacaaa caagggagaa gagtgtcaga atcagaatca tggagaaaat 1380gggcgggggt ggtgtgggtg atgggactca ttgtagaaag gaagccttgc tcattcttga 1440ggagcattaa ggtatttcga aactgccaag ggtgctggtg cggatggaca ctaatgcagc 1500cacgattgga gaatactttg cttcatagta ttggagcaca tgttactgct tcattttgga 1560gcttgtggag ttgatgactt tctgttttct gtttgtaaat tatttgctaa gcatattttc 1620tctaggcttt tttccttttg gggttctaca gtcgtaaaag agataataag attagttgga 1680cagtttaaag cttttattcg tcctttgaca aaagtaaatg ggagggcatt ccatcccttc 1740ctgaaggggg acactccatg agtgtctgtg agaggcagct atctgcactc taaactgcaa 1800acagaaatca ggtgttttaa gactgaatgt tttatttatc aaaatgtagc ttttggggag 1860ggaggggaaa tgtaatactg gaataatttg taaatgattt taattttata ttcagtgaaa 1920agattttatt tatggaatta accatttaat aaagaaatat ttacctaata aaaaaaaaaa 1980aaaaa 1985
<210>60<211>381<212>PRT<213>智人(Homo sapiens)<400>60Met Ser Ser Arg Ile Ala Arg Ala Leu Ala Leu Val Val Thr Leu Leu1 5 10 15His Leu Thr Arg Leu Ala Leu Ser Thr Cys Pro Ala Ala Cys His Cys20 25 30Pro Leu Glu Ala Pro Lys Cys Ala Pro Gly Val Gly Leu Val Arg Asp35 40 45Gly Cys Gly Cys Cys Lys Val Cys Ala Lys Gln Leu Asn Glu Asp Cys50 55 60Ser Lys Thr Gln Pro Cys Asp His Thr Lys Gly Leu Glu Cys Asn Phe65 70 75 80Gly Ala Ser Ser Thr Ala Leu Lys Gly Ile Cys Arg Ala Gln Ser Glu85 90 95Gly Arg Pro Cys Glu Tyr Asn Ser Arg Ile Tyr Gln Asn Gly Glu Ser100 105 110Phe Gln Pro Asn Cys Lys His Gln Cys Thr Cys Ile Asp Gly Ala Val115 120 125Gly Cys Ile Pro Leu Cys Pro Gln Glu Leu Ser Leu Pro Asn Leu Gly130 135 140Cys Pro Asn Pro Arg Leu Val Lys Val Thr Gly Gln Cys Cys Glu Glu145 150 155 160Trp Val Cys Asp Glu Asp Ser Ile Lys Asp Pro Met Glu Asp Gln Asp165 170 175Gly Leu Leu Gly Lys Glu Leu Gly Phe Asp Ala Ser Glu Val Glu Leu180 185 190Thr Arg Asn Asn Glu Leu Ile Ala Val Gly Lys Gly Ser Ser Leu Lys195 200 205Arg Leu Pro Val Phe Gly Met Glu Pro Arg Ile Leu Tyr Asn Pro Leu210 215 220Gln Gly Gln Lys Cys Ile Val Gln Thr Thr Ser Trp Ser Gln Cys Ser225 230 235 240Lys Thr Cys Gly Thr Gly Ile Ser Thr Arg Val Thr Asn Asp Asn Pro
245 250 255Glu Cys Arg Leu Val Lys Glu Thr Arg Ile Cys Glu Val Arg Pro Cys260 265 270Gly Gln Pro Val Tyr Ser Ser Leu Lys Lys Gly Lys Lys Cys Ser Lys275 280 285Thr Lys Lys Ser Pro Glu Pro Val Arg Phe Thr Tyr Ala Gly Cys Leu290 295 300Ser Val Lys Lys Tyr Arg Pro Lys Tyr Cys Gly Ser Cys Val Asp Gly305 310 315 320Arg Cys Cys Thr Pro Gln Leu Thr Arg Thr Val Lys Met Arg Phe Arg325 330 335Cys Glu Asp Gly Glu Thr Phe Ser Lys Asn Val Met Met Ile Gln Ser340 345 350Cys Lys Cys Asn Tyr Asn Cys Pro His Ala Asn Glu Ala Ala Phe Pro355 360 365Phe Tyr Arg Leu Phe Asn Asp Ile His Lys Phe Arg Asp370 375 380<210>61<211>2830<212>DNA<213>智人(Homo sapiens)<400>61cccacgcgtc cgctgggccc agctcccccg agaggtggtc ggatcctctg ggctgctcgg60tcgatgcctg tgccactgac gtccaggcat gaggtggttc ctgccctgga cgctggcagc 120agtgacagca gcagccgcca gcaccgtcct ggccacggcc ctctctccag cccctacgac 180catggacttt actccagctc cactggagga cacctcctca cgcccccaat tctgcaagtg 240gccatgtgag tgcccgccat ccccaccccg ctgcccgctg ggggtcagcc tcatcacaga 300tggctgtgag tgctgtaaga tgtgcgctca gcagcttggg gacaactgca cggaggctgc 360catctgtgac ccccaccggg gcctctactg tgactacagc ggggaccgcc cgaggtacgc 420aataggagtg tgtgcacagg tggtcggtgt gggctgcgtc ctggatgggg tgcgctacaa 480caacggccag tccttccagc ctaactgcaa gtacaactgc acgtgcatcg acggcgcggt 540gggctgcaca ccactgtgcc tccgagtgcg ccccccgcgt ctctggtgcc cccacccgcg 600gcgcgtgagc atacctggcc actgctgtga gcagtgggta tgtgaggacg acgccaagag 660gccacgcaag accgcacccc gtgacacagg agccttcgat gctgtgggtg aggtggaggc 720atggcacagg aactgcatag cctacacaag cccctggagc ccttgctcca ccagctgcgg 780cctgggggtc tccactcgga tctccaatgt taacgcccag tgctggcctg agcaagagag 840ccgcctctgc aacttgcggc catgcgatgt ggacatccat acactcatta aggcagggaa 900gaagtgtctg gctgtgtacc agccagaggc atccatgaac ttcacacttg cgggctgcat 960cagcacacgc tcctatcaac ccaagtactg tggagtttgc atggacaata ggtgctgcat 1020cccctacaag tctaagacta tcgacgtgtc cttccagtgt cctgatgggc ttggcttctc 1080ccgccaggtc ctatggatta atgcctgctt ctgtaacctg agctgtagga atcccaatga 1140catctttgct gacttggaat cctaccctga cttctcagaa attgccaact aggcaggcac 1200
aaatcttggg tcttggggac taacccaatg cctgtgaagc agtcagccct tatggccaat1260aacttttcac caatgagcct tagttaccct gatctggacc cttggcctcc atttctgtct1320ctaaccattc aaatgacgcc tgatggtgct gctcaggccc atgctatgag ttttctcctt1380gatatcattc agcatctact ctaaagaaaa atgcctgtct ctagctgttc tggactacac1440ccaagcctga tccagccttt ccaagtcact agaagtcctg ctggatcttg cctaaatccc1500aagaaatgga atcaggtaga cttttaatat cactaatttc ttctttagat gccaaaccac1560aagactcttt gggtccattc agatgaatag atggaatttg gaacaataga ataatctatt1620atttggagcc tgccaagagg tactgtaatg ggtaattctg acgtcagcgc accaaaacta1680tcctgattcc aaatatgtat gcacctcaag gtcatcaaac atttgccaag tgagttgaat1740agttgcttaa ttttgatttt taatggaaag ttgtatccat taacctgggc attgttgagg1800ttaagtttct cttcacccct acactgtgaa gggtacagat taggtttgtc ccagtcagaa1860ataaaatttg ataaacattc ctgttgatgg gaaaagcccc cagttaatac tccagagaca1920gggaaaggtc agcccatttc agaaggacca attgactctc acactgaatc agctgctgac1980tggcagggct ttgggcagtt ggccaggctc ttccttgaat cttctccctt gtcctgcttg2040ggttcatagg aattggtaag gcctctggac tggcctgtct ggcccctgag agtggtgccc2100tggaacactc ctctactctt acagagcctt gagagaccca gctgcagacc atgccagacc2160cactgaaatg accaagacag gttcaggtag gggtgtgggt caaaccaaga agtgggtgcc2220cttggtagca gcctggggtg acctctagag ctggaggctg tgggactcca ggggcccccg2280tgttcaggac acatctattg cagagactca tttcacagcc tttcgttctg ctgaccaaat2340ggccagtttt ctggtaggaa gatggaggtt taccagttgt ttagaaacag aaatagactt2400aataaaggtt taaagctgaa gaggttgaag ctaaaaggaa aaggttgttg ttaatgaata2460tcaggctatt atttattgta ttaggaaaat ataatattta ctgttagaat tcttttattt2520agggcctttt ctgtgccaga cattgctctc agtgctttgc atgtattagc tcactgaatc2580ttcacgacaa tgttgagaag ttcccattat tatttctgtt cttacaaatg tgaaacggaa2640gctcatagag gtgagaaaac tcaaccagag tcacccagtt ggtgactggg aaagttagga2700ttcagatcga aattggactg tctttataac ccatattttc cccctgtttt tagagcttcc2760aaatgtgtca gaataggaaa acattgcaat aaatggcttg attttttaaa aaaaaaaaaa2820aaaaaaaaaa 2830<210>62<211>367<212>PRT<213>智人(Homo sapiens)<400>62Met Arg Trp Phe Leu Pro Trp Thr Leu Ala Ala Val Thr Ala Ala Ala1 5 10 15Ala Ser Thr Val Leu Ala Thr Ala Leu Ser Pro Ala Pro Thr Thr Met20 25 30Asp Phe Thr Pro Ala Pro Leu Glu Asp Thr Ser Ser Arg Pro Gln Phe35 40 45Cys Lys Trp Pro Cys Glu Cys Pro Pro Ser Pro Pro Arg Cys Pro Leu50 55 60Gly Val Ser Leu Ile Thr Asp Gly Cys Glu Cys Cys Lys Met Cys Ala65 70 75 80Gln Gln Leu Gly Asp Asn Cys Thr Glu Ala Ala Ile Cys Asp Pro His85 90 95
Arg Gly Leu Tyr Cys Asp Tyr Ser Gly Asp Arg Pro Arg Tyr Ala Ile100 105 110Gly Val Cys Ala Gln Val Val Gly Val Gly Cys Val Leu Asp Gly Val115 120 125Arg Tyr Asn Asn Gly Gln Ser Phe Gln Pro Asn Cys Lys Tyr Asn Cys130 135 140Thr Cys Ile Asp Gly Ala Val Gly Cys Thr Pro Leu Cys Leu Arg Val145 150 155 160Arg Pro Pro Arg Leu Trp Cys Pro His Pro Arg Arg Val Ser Ile Pro165 170 175Gly His Cys Cys Glu Gln Trp Val Cys Glu Asp Asp Ala Lys Arg Pro180 185 190Arg Lys Thr Ala Pro Arg Asp Thr Gly Ala Phe Asp Ala Val Gly Glu195 200 205Val Glu Ala Trp His Arg Asn Cys Ile Ala Tyr Thr Ser Pro Trp Ser210 215 220Pro Cys Ser Thr Ser Cys Gly Leu Gly Val Ser Thr Arg Ile Ser Asn225 230 235 240Val Asn Ala Gln Cys Trp Pro Glu Gln Glu Ser Arg Leu Cys Asn Leu245 250 255Arg Pro Cys Asp Val Asp Ile His Thr Leu Ile Lys Ala Gly Lys Lys260 265 270Cys Leu Ala Val Tyr Gln Pro Glu Ala Ser Met Asn Phe Thr Leu Ala275 280 285Gly Cys Ile Ser Thr Arg Ser Tyr Gln Pro Lys Tyr Cys Gly Val Cys290 295 300Met Asp Asn Arg Cys Cys Ile Pro Tyr Lys Ser Lys Thr Ile Asp Val305 310 315 320Ser Phe Gln Cys Pro Asp Gly Leu Gly Phe Ser Arg Gln Val Leu Trp325 330 335Ile Asn Ala Cys Phe Cys Asn Leu Ser Cys Arg Asn Pro Asn Asp Ile340 345 350Phe Ala Asp Leu Glu Ser Tyr Pro Asp Phe Ser Glu Ile Ala Asn355 360 365
<210>63<211>1723<212>DNA<213>智人(Homo sapiens)<400>63tcgcggaggc ttggggcagc cgggtagctc ggaggtcgtg gcgctggggg ctagcaccag60cgctctgtcg ggaggcgcag cggttaggtg gaccggtcag cggactcacc ggccagggcg 120ctcggtgctg gaatttgata ttcattgatc cgggttttat ccctcttctt ttttcttaaa 180catttttttt taaaactgta ttgtttctcg ttttaattta tttttgcttg ccattcccca 240cttgaatcgg gccgacggct tggggagatt gctctacttc cccaaatcac tgtggatttt 300ggaaaccagc agaaagagga aagaggtagc aagagctcca gagagaagtc gaggaagaga 360gagacggggt cagagagagc gcgcgggcgt gcgagcagcg aaagcgacag gggcaaagtg 420agtgacctgc ttttgggggt gaccgccgga gcgcggcgtg agccctcccc cttgggatcc 480cgcagctgac cagtcgcgct gacggacaga cagacagaca ccgcccccag ccccagctac 540cacctcctcc ccggccggcg gcggacagtg gacgcggcgg cgagccgcgg gcaggggccg 600gagcccgcgc ccggaggcgg ggtggagggg gtcggggctc gcggcgtcgc actgaaactt 660ttcgtccaac ttctgggctg ttctcgcttc ggaggagccg tggtccgcgc gggggaagcc 720gagccgagcg gagccgcgag aagtgctagc tcgggccggg aggagccgca gccggaggag 780ggggaggagg aagaagagaa ggaagaggag agggggccgc agtggcgact cggcgctcgg 840aagccgggct catggacggg tgaggcggcg gtgtgcgcag acagtgctcc agccgcgcgc 900gctccccagg ccctggcccg ggcctcgggc cggggaggaa gagtagctcg ccgaggcgcc 960gaggagagcg ggccgcccca cagcccgagc cggagaggga gcgcgagccg cgccggcccc 1020ggtcgggcct ccgaaaccat gaactttctg ctgtcttggg tgcattggag ccttgccttg 1080ctgctctacc tccaccatgc caagtggtcc caggctgcac ccatggcaga aggaggaggg 1140cagaatcatc acgaagtggt gaagttcatg gatgtctatc agcgcagcta ctgccatcca 1200atcgagaccc tggtggacat cttccaggag taccctgatg agatcgagta catcttcaag 1260ccatcctgtg tgcccctgat gcgatgcggg ggctgctgca atgacgaggg cctggagtgt 1320gtgcccactg aggagtccaa catcaccatg cagattatgc ggatcaaacc tcaccaaggc 1380cagcacatag gagagatgag cttcctacag cacaacaaat gtgaatgcag accaaagaaa 1440gatagagcaa gacaagaaaa aaaatcagtt cgaggaaagg gaaaggggca aaaacgaaag 1500cgcaagaaat cccggtataa gtcctggagc gttccctgtg ggccttgctc agagcggaga 1560aagcatttgt ttgtacaaga tccgcagacg tgtaaatgtt cctgcaaaaa cacagactcg 1620cgttgcaagg cgaggcagct tgagttaaac gaacgtactt gcagatgtga caagccgagg 1680cggtgagccg ggcaggagga aggagcctcc ctcagggttt cgg1723<210>64<211>215<212>PRT<213>智人(Homo sapiens)<400>64Met Asn Phe Leu Leu Ser Trp Val His Trp Ser Leu Ala Leu Leu Leu1 5 10 15Tyr Leu His His Ala Lys Trp Ser Gln Ala Ala Pro Met Ala Glu Gly20 25 30Gly Gly Gln Asn His His Glu Val Val Lys Phe Met Asp Val Tyr Gln35 40 45Arg Ser Tyr Cys His Pro Ile Glu Thr Leu Val Asp Ile Phe Gln Glu
50 55 60Tyr Pro Asp Glu Ile Glu Tyr Ile Phe Lys Pro Ser Cys Val Pro Leu65 70 75 80Met Arg Cys Gly Gly Cys Cys Asn Asp Glu Gly Leu Glu Cys Val Pro85 90 95Thr Glu Glu Ser Asn Ile Thr Met Gln Ile Met Arg Ile Lys Pro His100 105 110Gln Gly Gln His Ile Gly Glu Met Ser Phe Leu Gln His Asn Lys Cys115 120 125Glu Cys Arg Pro Lys Lys Asp Arg Ala Arg Gln Glu Lys Lys Ser Val130 135 140Arg Gly Lys Gly Lys Gly Gln Lys Arg Lys Arg Lys Lys Ser Arg Tyr145 150 155 160Lys Ser Trp Ser Val Pro Cys Gly Pro Cys Ser Glu Arg Arg Lys His165 170 175Leu Phe Val Gln Asp Pro Gln Thr Cys Lys Cys Ser Cys Lys Asn Thr180 185 190Asp Ser Arg Cys Lys Ala Arg Gln Leu Glu Leu Asn Glu Arg Thr Cys195 200 205Arg Cys Asp Lys Pro Arg Arg210 215<210>65<211>1172<212>DNA<213>智人(Homo sapiens)<400>65gcgatgcggg cgcccccggc gggcggcccc ggcgggcacc atgagccctc tgctccgccg60cctgctgctc gccgcactcc tgcagctggc ccccgcccag gcccctgtct cccagcctga 120tgcccctggc caccagagga aagtggtgtc atggatagat gtgtatactc gcgctacctg 180ccagccccgg gaggtggtgg tgcccttgac tgtggagctc atgggcaccg tggccaaaca 240gctggtgccc agctgcgtga ctgtgcagcg ctgtggtggc tgctgccctg acgatggcct 300ggagtgtgtg cccactgggc agcaccaagt ccggatgcag atcctcatga tccggtaccc 360gagcagtcag ctgggggaga tgtccctgga agaacacagc cagtgtgaat gcagacctaa 420aaaaaaggac agtgctgtga agccagacag ggctgccact ccccaccacc gtccccagcc 480ccgttctgtt ccgggctggg actctgcccc cggagcaccc tccccagctg acatcaccca 540tcccactcca gccccaggcc cctctgccca cgctgcaccc agcaccacca gcgccctgac 600ccccggacct gccgctgccg ctgccgacgc cgcagcttcc tccgttgcca agggcggggc 660ttagagctca acccagacac ctgcaggtgc cggaagctgc gaaggtgaca catggctttt 720cagactcagc agggtgactt gcctcagagg ctatatccca gtgggggaac aaagaggagc 780ctggtaaaaa acagccaagc ccccaagacc tcagcccagg cagaagctgc tctaggacct 840
gggcctctca gagggctctt ctgccatccc ttgtctccct gaggccatca tcaaacagga 900cagagttgga agaggagact gggaggcagc aagaggggtc acataccagc tcaggggaga 960atggagtact gtctcagttt ctaaccactc tgtgcaagta agcatcttac aactggctct 1020tcctcccctc actaagaaga cccaaacctc tgcataatgg gatttgggct ttggtacaag 1080aactgtgacc cccaaccctg ataaaagaga tggaaggaaa aaaaaaaaaa aaaaaaaaaa 1140aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aa1172<210>66<211>207<212>PRT<213>智人(Homo sapiens)<400>66Met Ser Pro Leu Leu Arg Arg Leu Leu Leu Ala Ala Leu Leu Gln Leu1 5 10 15Ala Pro Ala Gln Ala Pro Val Ser Gln Pro Asp Ala Pro Gly His Gln20 25 30Arg Lys Val Val Ser Trp Ile Asp Val Tyr Thr Arg Ala Thr Cys Gln35 40 45Pro Arg Glu Val Val Val Pro Leu Thr Val Glu Leu Met Gly Thr Val50 55 60Ala Lys Gln Leu Val Pro Ser Cys Val Thr Val Gln Arg Cys Gly Gly65 70 75 80Cys Cys Pro Asp Asp Gly Leu Glu Cys Val Pro Thr Gly Gln His Gln85 90 95Val Arg Met Gln Ile Leu Met Ile Arg Tyr Pro Ser Ser Gln Leu Gly100 105 110Glu Met Ser Leu Glu Glu His Ser Gln Cys Glu Cys Arg Pro Lys Lys115 120 125Lys Asp Ser Ala Val Lys Pro Asp Arg Ala Ala Thr Pro His His Arg130 135 140Pro Gln Pro Arg Ser Val Pro Gly Trp Asp Ser Ala Pro Gly Ala Pro145 150 155 160Ser Pro Ala Asp Ile Thr His Pro Thr Pro Ala Pro Gly Pro Ser Ala165 170 175His Ala Ala Pro Ser Thr Thr Ser Ala Leu Thr Pro Gly Pro Ala Ala180 185 190Ala Ala Ala Asp Ala Ala Ala Ser Ser Val Ala Lys Gly Gly Ala195 200 205
<210>67<211>2076<212>DNA<213>智人(Homo sapiens)<400>67cggggaaggg gagggaggag ggggacgagg gctctggcgg gtttggaggg gctgaacatc 60gcggggtgtt ctggtgtccc ccgccccgcc tctccaaaaa gctacaccga cgcggaccgc 120ggcggcgtcc tccctcgccc tcgcttcacc tcgcgggctc cgaatgcggg gagctcggat 180gtccggtttc ctgtgaggct tttacctgac acccgccgcc tttccccggc actggctggg 240agggcgccct gcaaagttgg gaacgcggag ccccggaccc gctcccgccg cctccggctc 300gcccaggggg ggtcgccggg aggagcccgg gggagaggga ccaggagggg cccgcggcct 360cgcaggggcg cccgcgcccc cacccctgcc cccgccagcg gaccggtccc ccacccccgg 420tccttccacc atgcacttgc tgggcttctt ctctgtggcg tgttctctgc tcgccgctgc 480gctgctcccg ggtcctcgcg aggcgcccgc cgccgccgcc gccttcgagt ccggactcga 540cctctcggac gcggagcccg acgcgggcga ggccacggct tatgcaagca aagatctgga 600ggagcagtta cggtctgtgt ccagtgtaga tgaactcatg actgtactct acccagaata 660ttggaaaatg tacaagtgtc agctaaggaa aggaggctgg caacataaca gagaacaggc 720caacctcaac tcaaggacag aagagactat aaaatttgct gcagcacatt ataatacaga 780gatcttgaaa agtattgata atgagtggag aaagactcaa tgcatgccac gggaggtgtg 840tatagatgtg gggaaggagt ttggagtcgc gacaaacacc ttctttaaac ctccatgtgt 900gtccgtctac agatgtgggg gttgctgcaa tagtgagggg ctgcagtgca tgaacaccag 960cacgagctac ctcagcaaga cgttatttga aattacagtg cctctctctc aaggccccaa1020accagtaaca atcagttttg ccaatcacac ttcctgccga tgcatgtcta aactggatgt1080ttacagacaa gttcattcca ttattagacg ttccctgcca gcaacactac cacagtgtca1140ggcagcgaac aagacctgcc ccaccaatta catgtggaat aatcacatct gcagatgcct1200ggctcaggaa gattttatgt tttcctcgga tgctggagat gactcaacag atggattcca1260tgacatctgt ggaccaaaca aggagctgga tgaagagacc tgtcagtgtg tctgcagagc1320ggggcttcgg cctgccagct gtggacccca caaagaacta gacagaaact catgccagtg1380tgtctgtaaa aacaaactct tccccagcca atgtggggcc aaccgagaat ttgatgaaaa1440cacatgccag tgtgtatgta aaagaacctg ccccagaaat caacccctaa atcctggaaa1500atgtgcctgt gaatgtacag aaagtccaca gaaatgcttg ttaaaaggaa agaagttcca1560ccaccaaaca tgcagctgtt acagacggcc atgtacgaac cgccagaagg cttgtgagcc1620aggattttca tatagtgaag aagtgtgtcg ttgtgtccct tcatattgga aaagaccaca1680aatgagctaa gattgtactg ttttccagtt catcgatttt ctattatgga aaactgtgtt1740gccacagtag aactgtctgt gaacagagag acccttgtgg gtccatgcta acaaagacaa1800aagtctgtct ttcctgaacc atgtggataa ctttacagaa atggactgga gctcatctgc1860aaaaggcctc ttgtaaagac tggttttctg ccaatgacca aacagccaag attttcctct1920tgtgatttct ttaaaagaat gactatataa tttatttcca ctaaaaatat tgtttctgca1980ttcattttta tagcaacaac aattggtaaa actcactgtg atcaatattt ttatatcatg2040caaaatatgt ttaaaataaa atgaaaattg tattat 2076<210>68<211>419<212>PRT<213>智人(Homo sapiens)<400>68Met His Leu Leu Gly Phe Phe Ser Val Ala Cys Ser Leu Leu Ala Ala1 5 10 15Ala Leu Leu Pro Gly Pro Arg Glu Ala Pro Ala Ala Ala Ala Ala Phe
20 25 30Glu Ser Gly Leu Asp Leu Ser Asp Ala Glu Pro Asp Ala Gly Glu Ala35 40 45Thr Ala Tyr Ala Ser Lys Asp Leu Glu Glu Gln Leu Arg Ser Val Ser50 55 60Ser Val Asp Glu Leu Met Thr Val Leu Tyr Pro Glu Tyr Trp Lys Met65 70 75 80Tyr Lys Cys Gln Leu Arg Lys Gly Gly Trp Gln His Asn Arg Glu Gln85 90 95Ala Asn Leu Asn Ser Arg Thr Glu Glu Thr Ile Lys Phe Ala Ala Ala100 105 110His Tyr Asn Thr Glu Ile Leu Lys Ser Ile Asp Asn Glu Trp Arg Lys115 120 125Thr Gln Cys Met Pro Arg Glu Val Cys Ile Asp Val Gly Lys Glu Phe130 135 140Gly Val Ala Thr Asn Thr Phe Phe Lys Pro Pro Cys Val Ser Val Tyr145 150 155 160Arg Cys Gly Gly Cys Cys Asn Ser Glu Gly Leu Gln Cys Met Asn Thr165 170 175Ser Thr Ser Tyr Leu Ser Lys Thr Leu Phe Glu Ile Thr Val Pro Leu180 185 190Ser Gln Gly Pro Lys Pro Val Thr Ile Ser Phe Ala Asn His Thr Ser195 200 205Cys Arg Cys Met Ser Lys Leu Asp Val Tyr Arg Gln Val His Ser Ile210 215 220Ile Arg Arg Ser Leu Pro Ala Thr Leu Pro Gln Cys Gln Ala Ala Asn225 230 235 240Lys Thr Cys Pro Thr Asn Tyr Met Trp Asn Asn His Ile Cys Arg Cys245 250 255Leu Ala Gln Glu Asp Phe Met Phe Ser Ser Asp Ala Gly Asp Asp Ser260 265 270Thr Asp Gly Phe His Asp Ile Cys Gly Pro Asn Lys Glu Leu Asp Glu275 280 285Glu Thr Cys Gln Cys Val Cys Arg Ala Gly Leu Arg Pro Ala Ser Cys290 295 300
Gly Pro His Lys Glu Leu Asp Arg Asn Ser Cys Gln Cys Val Cys Lys305 310 315 320Asn Lys Leu Phe Pro Ser Gln Cys Gly Ala Asn Arg Glu Phe Asp Glu325 330 335Asn Thr Cys Gln Cys Val Cys Lys Arg Thr Cys Pro Arg Asn Gln Pro340 345 350Leu Asn Pro Gly Lys Cys Ala Cys Glu Cys Thr Glu Ser Pro Gln Lys355 360 365Cys Leu Leu Lys Gly Lys Lys Phe His His Gln Thr Cys Ser Cys Tyr370 375 380Arg Arg Pro Cys Thr Asn Arg Gln Lys Ala Cys Glu Pro Gly Phe Ser385 390 395 400Tyr Ser Glu Glu Val Cys Arg Cys Val Pro Ser Tyr Trp Lys Arg Pro405 410 415Gln Met Ser<210>69<211>2029<212>DNA<213>智人(Homo sapiens)<400>69gttgggttcc agctttctgt agctgtaagc attggtggcc acaccacctc cttacaaagc 60aactagaacc tgcggcatac attggagaga tttttttaat tttctggaca tgaagtaaat120ttagagtgct ttctaatttc aggtagaaga catgtccacc ttctgattat ttttggagaa180cattttgatt tttttcatct ctctctcccc acccctaaga ttgtgcaaaa aaagcgtacc240ttgcctaatt gaaataattt cattggattt tgatcagaac tgattatttg gttttctgtg300tgaagttttg aggtttcaaa ctttccttct ggagaatgcc ttttgaaaca attttctcta360gctgcctgat gtcaactgct tagtaatcag tggatattga aatattcaaa atgtacagag420agtgggtagt ggtgaatgtt ttcatgatgt tgtacgtcca gctggtgcag ggctccagta480atgaacatgg accagtgaag cgatcatctc agtccacatt ggaacgatct gaacagcaga540tcagggctgc ttctagtttg gaggaactac ttcgaattac tcactctgag gactggaagc600tgtggagatg caggctgagg ctcaaaagtt ttaccagtat ggactctcgc tcagcatccc660atcggtccac taggtttgcg gcaactttct atgacattga aacactaaaa gttatagatg720aagaatggca aagaactcag tgcagcccta gagaaacgtg cgtggaggtg gccagtgagc780tggggaagag taccaacaca ttcttcaagc ccccttgtgt gaacgtgttc cgatgtggtg840gctgttgcaa tgaagagagc cttatctgta tgaacaccag cacctcgtac atttccaaac900agctctttga gatatcagtg cctttgacat cagtacctga attagtgcct gttaaagttg960ccaatcatac aggttgtaag tgcttgccaa cagccccccg ccatccatac tcaattatca 1020gaagatccat ccagatccct gaagaagatc gctgttccca ttccaagaaa ctctgtccta 1080ttgacatgct atgggatagc aacaaatgta aatgtgtttt gcaggaggaa aatccacttg 1140ctggaacaga agaccactct catctccagg aaccagctct ctgtgggcca cacatgatgt 1200ttgacgaaga tcgttgcgag tgtgtctgta aaacaccatg tcccaaagat ctaatccagc 1260
accccaaaaa ctgcagttgc tttgagtgca aagaaagtct ggagacctgc tgccagaagc1320acaagctatt tcacccagac acctgcagct gtgaggacag atgccccttt cataccagac1380catgtgcaag tggcaaaaca gcatgtgcaa agcattgccg ctttccaaag gagaaaaggg1440ctgcccaggg gccccacagc cgaaagaatc cttgattcag cgttccaagt tccccatccc1500tgtcattttt aacagcatgc tgctttgcca agttgctgtc actgtttttt tcccaggtgt1560taaaaaaaaa atccatttta cacagcacca cagtgaatcc agaccaacct tccattcaca1620ccagctaagg agtccctggt tcattgatgg atgtcttcta gctgcagatg cctctgcgca1680ccaaggaatg gagaggaggg gacccatgta atccttttgt ttagttttgt ttttgttttt1740tggtgaatga gaaaggtgtg ctggtcatgg aatggcaggt gtcatatgac tgattactca1800gagcagatga ggaaaactgt agtctctgag tcctttgcta atcgcaactc ttgtgaatta1860ttctgattct tttttatgca gaatttgatt cgtatgatca gtactgactt tctgattact1920gtccagctta tagtcttcca gtttaatgaa ctaccatctg atgtttcata tttaagtgta1980tttaaagaaa ataaacacca ttattcaagc caaaaaaaaa aaaaaaaaa2029<210>70<211>354<212>PRT<213>智人(Homo sapiens)<400>70Met Tyr Arg Glu Trp Val Val Val Asn Val Phe Met Met Leu Tyr Val1 5 10 15Gln Leu Val Gln Gly Ser Ser Asn Glu His Gly Pro Val Lys Arg Ser20 25 30Ser Gln Ser Thr Leu Glu Arg Ser Glu Gln Gln Ile Arg Ala Ala Ser35 40 45Ser Leu Glu Glu Leu Leu Arg Ile Thr His Ser Glu Asp Trp Lys Leu50 55 60Trp Arg Cys Arg Leu Arg Leu Lys Ser Phe Thr Ser Met Asp Ser Arg65 70 75 80Ser Ala Ser His Arg Ser Thr Arg Phe Ala Ala Thr Phe Tyr Asp Ile85 90 95Glu Thr Leu Lys Val Ile Asp Glu Glu Trp Gln Arg Thr Gln Cys Ser100 105 110Pro Arg Glu Thr Cys Val Glu Val Ala Ser Glu Leu Gly Lys Ser Thr115 120 125Asn Thr Phe Phe Lys Pro Pro Cys Val Asn Val Phe Arg Cys Gly Gly130 135 140Cys Cys Asn Glu Glu Ser Leu Ile Cys Met Asn Thr Ser Thr Ser Tyr145 150 155 160Ile Ser Lys Gln Leu Phe Glu Ile Ser Val Pro Leu Thr Ser Val Pro165 170 175
Glu Leu Val Pro Val Lys Val Ala Asn His Thr Gly Cys Lys Cys Leu180 185 190Pro Thr Ala Pro Arg His Pro Tyr Ser Ile Ile Arg Arg Ser Ile Gln195 200 205Ile Pro Glu Glu Asp Arg Cys Ser His Ser Lys Lys Leu Cys Pro Ile210 215 220Asp Met Leu Trp Asp Ser Asn Lys Cys Lys Cys Val Leu Gln Glu Glu225 230 235 240Asn Pro Leu Ala Gly Thr Glu Asp His Ser His Leu Gln Glu Pro Ala245 250 255Leu Cys Gly Pro His Met Met Phe Asp Glu Asp Arg Cys Glu Cys Val260 265 270Cys Lys Thr Pro Cys Pro Lys Asp Leu Ile Gln His Pro Lys Asn Cys275 280 285Ser Cys Phe Glu Cys Lys Glu Ser Leu Glu Thr Cys Cys Gln Lys His290 295 300Lys Leu Phe His Pro Asp Thr Cys Ser Cys Glu Asp Arg Cys Pro Phe305 310 315 320His Thr Arg Pro Cys Ala Ser Gly Lys Thr Ala Cys Ala Lys His Cys325 330 335Arg Phe Pro Lys Glu Lys Arg Ala Ala Gln Gly Pro His Ser Arg Lys340 345 350Asn Pro<210>71<211>2825<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(2689)..(2689)<223>n是a，c，g或t<400>71gacgcgtggg cggacgcgtg ggctggttca ggtccaggtt ttgctttgat ccttttcaaa 60aactggagac acagaagagg gctctaggaa aaagttttgg atgggattat gtggaaacta120ccctgcgatt ctctgctgcc agagcaggct cggcgcttcc accccagtgc agccttcccc180
tggcggtggt gaaagagact cgggagtcgc tgcttccaaa gtgcccgccg tgagtgagct 240ctcaccccag tcagccaaat gagcctcttc gggcttctcc tgctgacatc tgccctggcc 300ggccagagac aggggactca ggcggaatcc aacctgagta gtaaattcca gttttccagc 360aacaaggaac agaacggagt acaagatcct cagcatgaga gaattattac tgtgtctact 420aatggaagta ttcacagccc aaggtttcct catacttatc caagaaatac ggtcttggta 480tggagattag tagcagtaga ggaaaatgta tggatacaac ttacgtttga tgaaagattt 540gggcttgaag acccagaaga tgacatatgc aagtatgatt ttgtagaagt tgaggaaccc 600agtgatggaa ctatattagg gcgctggtgt ggttctggta ctgtaccagg aaaacagatt 660tctaaaggaa atcaaattag gataagattt gtatctgatg aatattttcc ttctgaacca 720gggttctgca tccactacaa cattgtcatg ccacaattca cagaagctgt gagtccttca 780gtgctacccc cttcagcttt gccactggac ctgcttaata atgctataac tgcctttagt 840accttggaag accttattcg atatcttgaa ccagagagat ggcagttgga cttagaagat 900ctatataggc caacttggca acttcttggc aaggcttttg tttttggaag aaaatccaga 960gtggtggatc tgaaccttct aacagaggag gtaagattat acagctgcac acctcgtaac1020ttctcagtgt ccataaggga agaactaaag agaaccgata ccattttctg gccaggttgt1080ctcctggtta aacgctgtgg tgggaactgt gcctgttgtc tccacaattg caatgaatgt1140caatgtgtcc caagcaaagt tactaaaaaa taccacgagg tccttcagtt gagaccaaag1200accggtgtca ggggattgca caaatcactc accgacgtgg ccctggagca ccatgaggag1260tgtgactgtg tgtgcagagg gagcacagga ggatagccgc atcaccacca gcagctcttg1320cccagagctg tgcagtgcag tggctgattc tattagagaa cgtatgcgtt atctccatcc1380ttaatctcag ttgtttgctt caaggacctt tcatcttcag gatttacagt gcattctgaa1440agaggagaca tcaaacagaa ttaggagttg tgcaacagct cttttgagag gaggcctaaa1500ggacaggaga aaaggtcttc aatcgtggaa agaaaattaa atgttgtatt aaatagatca1560ccagctagtt tcagagttac catgtacgta ttccactagc tgggttctgt atttcagttc1620tttcgatacg gcttagggta atgtcagtac aggaaaaaaa ctgtgcaagt gagcacctga1680ttccgttgcc ttgcttaact ctaaagctcc atgtcctgggcctaaaatcg tataaaatct 1740ggattttttt tttttttttt gctcatattc acatatgtaa accagaacat tctatgtact1800acaaacctgg tttttaaaaa ggaactatgt tgctatgaat taaacttgtg tcatgctgat1860aggacagact ggatttttca tatttcttat taaaatttct gccatttaga agaagagaac1920tacattcatg gtttggaaga gataaacctg aaaagaagag tggccttatc ttcactttat1980cgataagtca gtttatttgt ttcattgtgt acatttttat attctccttt tgacattata2040actgttggct tttctaatct tgttaaatat atctattttt accaaaggta tttaatattc2100ttttttatga caacttagat caactatttt tagcttggta aatttttcta aacacaattg2160ttatagccag aggaacaaag atgatataaa atattgttgc tctgacaaaa atacatgtat2220ttcattctcg tatggtgcta gagttagatt aatctgcatt ttaaaaaact gaattggaat2280agaattggta agttgcaaag actttttgaa aataattaaa ttatcatatc ttccattcct2340gttattggag atgaaaataa aaagcaactt atgaaagtag acattcagat ccagccatta2400ctaacctatt ccttttttgg ggaaatctga gcctagctca gaaaaacata aagcaccttg2460aaaaagactt ggcagcttcc tgataaagcg tgctgtgctg tgcagtagga acacatccta2520tttattgtga tgttgtggtt ttattatctt aaactctgtt ccatacactt gtataaatac2580atggatattt ttatgtacag aagtatgtct cttaaccagt tcacttattg tactctggca2640atttaaaaga aaatcagtaa aatattttgc ttgtaaaatg cttaatatng tgcctaggtt2700atgtggtgac tatttgaatc aaaaatgtat tgaatcatca aataaaagaa tgtggctatt2760ttggggagaa aattaaaaaa aaaaaaaaaa aaaaaggttt agggataaca gggtaatgcg2820gccgc2825<210>72<211>345<212>PRT<213>智人(Homo sapiens)<400>72
Met Ser Leu Phe Gly Leu Leu Leu Leu Thr Ser Ala Leu Ala Gly Gln1 5 10 15Arg Gln Gly Thr Gln Ala Glu Ser Asn Leu Ser Ser Lys Phe Gln Phe20 25 30Ser Ser Asn Lys Glu Gln Asn Gly Val Gln Asp Pro Gln His Glu Arg35 40 45Ile Ile Thr Val Ser Thr Asn Gly Ser Ile His Ser Pro Arg Phe Pro50 55 60His Thr Tyr Pro Arg Asn Thr Val Leu Val Trp Arg Leu Val Ala Val65 70 75 80Glu Glu Asn Val Trp Ile Gln Leu Thr Phe Asp Glu Arg Phe Gly Leu85 90 95Glu Asp Pro Glu Asp Asp Ile Cys Lys Tyr Asp Phe Val Glu Val Glu100 105 110Glu Pro Ser Asp Gly Thr Ile Leu Gly Arg Trp Cys Gly Ser Gly Thr115 120 125Val Pro Gly Lys Gln Ile Ser Lys Gly Asn Gln Ile Arg Ile Arg Phe130 135 140Val Ser Asp Glu Tyr Phe Pro Ser Glu Pro Gly Phe Cys Ile His Tyr145 150 155 160Asn Ile Val Met Pro Gln Phe Thr Glu Ala Val Ser Pro Ser Val Leu165 170 175Pro Pro Ser Ala Leu Pro Leu Asp Leu Leu Asn Asn Ala Ile Thr Ala180 185 190Phe Ser Thr Leu Glu Asp Leu Ile Arg Tyr Leu Glu Pro Glu Arg Trp195 200 205Gln Leu Asp Leu Glu Asp Leu Tyr Arg Pro Thr Trp Gln Leu Leu Gly210 215 220Lys Ala Phe Val Phe Gly Arg Lys Ser Arg Val Val Asp Leu Asn Leu225 230 235 240Leu Thr Glu Glu Val Arg Leu Tyr Ser Cys Thr Pro Arg Asn Phe Ser245 250 255Val Ser Ile Arg Glu Glu Leu Lys Arg Thr Asp Thr Ile Phe Trp Pro260 265 270Gly Cys Leu Leu Val Lys Arg Cys Gly Gly Asn Cys Ala Cys Cys Leu
275 280 285His Asn Cys Asn Glu Cys Gln Cys Val Pro Ser Lys Val Thr Lys Lys290 295 300Tyr His Glu Val Leu Gln Leu Arg Pro Lys Thr Gly Val Arg Gly Leu305 310 315 320His Lys Ser Leu Thr Asp Val Ala Leu Glu His His Glu Glu Cys Asp325 330 335Cys Val Cys Arg Gly Ser Thr Gly Gly340 345<210>73<211>2745<212>DNA<213>智人(Homo sapiens)<400>73acctccctcc gcggagcagc cagacagcga gggccccggc cgggggcagg ggggacgccc 60cgtccggggc accccccccg gctctgagcc gcccgcgggg ccggcctcgg cccggagcgg120aggaaggagt cgccgaggag cagcctgagg ccccagagtc tgagacgagc cgccgccgcc180cccgccactg cggggaggag ggggaggagg agcgggagga gggacgagct ggtcgggaga240agaggaaaaa aacttttgag acttttccgt tgccgctggg agccggaggc gcggggacct300cttggcgcga cgctgccccg cgaggaggca ggacttgggg accccagacc gcctcccttt360gccgccgggg acgcttgctc cctccctgcc ccctacacgg cgtccctcag gcgcccccat420tccggaccag ccctcgggag tcgccgaccc ggcctcccgc aaagactttt ccccagacct480cgggcgcacc ccctgcacgc cgccttcatc cccggcctgt ctcctgagcc cccgcgcatc540ctagaccctt tctcctccag gagacggatc tctctccgac ctgccacaga tcccctattc600aagaccaccc accttctggt accagatcgc gcccatctag gttatttccg tgggatactg660agacaccccc ggtccaagcc tcccctccac cactgcgccc ttctccctga ggagcctcag720ctttccctcg aggccctcct accttttgcc gggagacccc cagcccctgc aggggcgggg780cctccccacc acaccagccc tgttcgcgct ctcggcagtg ccggggggcg ccgcctcccc840catgccgccc tccgggctgc ggctgctgcc gctgctgcta ccgctgctgt ggctactggt900gctgacgcct ggcccgccgg ccgcgggact atccacctgc aagactatcg acatggagct960ggtgaagcgg aagcgcatcg aggccatccg cggccagatc ctgtccaagc tgcggctcgc 1020cagccccccg agccaggggg aggtgccgcc cggcccgctg cccgaggccg tgctcgccct 1080gtacaacagc acccgcgacc gggtggccgg ggagagtgca gaaccggagc ccgagcctga 1140ggccgactac tacgccaagg aggtcacccg cgtgctaatg gtggaaaccc acaacgaaat 1200ctatgacaag ttcaagcaga gtacacacag catatatatg ttcttcaaca catcagagct 1260ccgagaagcg gtacctgaac ccgtgttgct ctcccgggca gagctgcgtc tgctgaggag 1320gctcaagtta aaagtggagc agcacgtgga gctgtaccag aaatacagca acaattcctg 1380gcgatacctc agcaaccggc tgctggcacc cagcgactcg ccagagtggt tatcttttga 1440tgtcaccgga gttgtgcggc agtggttgag ccgtggaggg gaaattgagg gctttcgcct 1500tagcgcccac tgctcctgtg acagcaggga taacacactg caagtggaca tcaacgggtt 1560cactaccggc cgccgaggtg acctggccac cattcatggc atgaaccggc ctttcctgct 1620tctcatggcc accccgctgg agagggccca gcatctgcaa agctcccggc accgccgagc 1680cctggacacc aactattgct tcagctccac ggagaagaac tgctgcgtgc ggcagctgta 1740cattgacttc cgcaaggacc tcggctggaa gtggatccac gagcccaagg gctaccatgc 1800caacttctgc ctcgggccct gcccctacat ttggagcctg gacacgcagt acagcaaggt 1860cctggccctg tacaaccagc ataacccggg cgcctcggcg gcgccgtgct gcgtgccgca 1920
ggcgctggag ccgctgccca tcgtgtacta cgtgggccgc aagcccaagg tggagcagct 1980gtccaacatg atcgtgcgct cctgcaagtg cagctgaggt cccgccccgc cccgccccgc 2040cccggcaggc ccggccccac cccgccccgc ccccgctgcc ttgcccatgg gggctgtatt 2100taaggacacc gtgccccaag cccacctggg gccccattaa agatggagag aggactgcgg 2160atctctgtgt cattgggcgc ctgcctgggg tctccatccc tgacgttccc ccactcccac 2220tccctctctc tccctctctg cctcctcctg cctgtctgca ctattccttt gcccggcatc 2280aaggcacagg ggaccagtgg ggaacactac tgtagttaga tctatttatt gagcaccttg 2340ggcactgttg aagtgcctta cattaatgaa ctcattcagt caccatagca acactctgag 2400atggcaggga ctctgataac acccatttta aaggttgagg aaacaagccc agagaggtta 2460agggaggagt tcctgcccac caggaacctg ctttagtggg ggatagtgaa gaagacaata 2520aaagatagta gttcaggcca ggcggggtgc tcacgcctgt aatcctagca cttttgggag 2580gcagagatgg gaggatactt gaatccaggc atttgagacc agcctgggta acatagtgag 2640accctatctc tacaaaacac ttttaaaaaa tgtacacctg tggtcccagc tactctggag 2700gctaaggtgg gaggatcact tgatcctggg aggtcaaggc tgcag 2745<210>74<211>391<212>PRT<213>智人(Homo sapiens)<400>74Met Pro Pro Ser Gly Leu Arg Leu Leu Pro Leu Leu Leu Pro Leu Leu1 5 10 15Trp Leu Leu Val Leu Thr Pro Gly Pro Pro Ala Ala Gly Leu Ser Thr20 25 30Cys Lys Thr Ile Asp Met Glu Leu Val Lys Arg Lys Arg Ile Glu Ala35 40 45Ile Arg Gly Gln Ile Leu Ser Lys Leu Arg Leu Ala Ser Pro Pro Ser50 55 60Gln Gly Glu Val Pro Pro Gly Pro Leu Pro Glu Ala Val Leu Ala Leu65 70 75 80Tyr Asn Ser Thr Arg Asp Arg Val Ala Gly Glu Ser Ala Glu Pro Glu85 90 95Pro Glu Pro Glu Ala Asp Tyr Tyr Ala Lys Glu Val Thr Arg Val Leu100 105 110Met Val Glu Thr His Asn Glu Ile Tyr Asp Lys Phe Lys Gln Ser Thr115 120 125His Ser Ile Tyr Met Phe Phe Asn Thr Ser Glu Leu Arg Glu Ala Val130 135 140Pro Glu Pro Val Leu Leu Ser Arg Ala Glu Leu Arg Leu Leu Arg Arg145 150 155 160Leu Lys Leu Lys Val Glu Gln His Val Glu Leu Tyr Gln Lys Tyr Ser
165 170 175Asn Asn Ser Trp Arg Tyr Leu Ser Asn Arg Leu Leu Ala Pro Ser Asp180 185 190Ser Pro Glu Trp Leu Ser Phe Asp Val Thr Gly Val Val Arg Gln Trp195 200 205Leu Ser Arg Gly Gly Glu Ile Glu Gly Phe Arg Leu Ser Ala His Cys210 215 220Ser Cys Asp Ser Arg Asp Asn Thr Leu Gln Val Asp Ile Asn Gly Phe225 230 235 240Thr Thr Gly Arg Arg Gly Asp Leu Ala Thr Ile His Gly Met Asn Arg245 250 255Pro Phe Leu Leu Leu Met Ala Thr Pro Leu Glu Arg Ala Gln His Leu260 265 270Gln Ser Ser Arg His Arg Arg Ala Leu Asp Thr Asn Tyr Cys Phe Ser275 280 285Ser Thr Glu Lys Asn Cys Cys Val Arg Gln Leu Tyr Ile Asp Phe Arg290 295 300Lys Asp Leu Gly Trp Lys Trp Ile His Glu Pro Lys Gly Tyr His Ala305 310 315 320Asn Phe Cys Leu Gly Pro Cys Pro Tyr Ile Trp Ser Leu Asp Thr Gln325 330 335Tyr Ser Lys Val Leu Ala Leu Tyr Asn Gln His Asn Pro Gly Ala Ser340 345 350Ala Ala Pro Cys Cys Val Pro Gln Ala Leu Glu Pro Leu Pro Ile Val355 360 365Tyr Tyr Val Gly Arg Lys Pro Lys Val Glu Gln Leu Ser Asn Met Ile370 375 380Val Arg Ser Cys Lys Cys Ser385 390<210>75<211>336<212>DNA<213>智人(Homo sapiens)<400>75gccctggaca ccaactattg cttcagctcc acggagaaga actgctgcgt gcggcagctg 60tacattgact tccgcaagga cctcggctgg aagtggatcc acgagcccaa gggctaccat120
gccaacttct gcctcgggcc ctgcccctac atttggagcc tggacacgca gtacagcaag 180gtcctggccc tgtacaacca gcataacccg ggcgcctcgg cggcgccgtg ctgcgtgccg 240caggcgctgg agccgctgcc catcgtgtac tacgtgggcc gcaagcccaa ggtggagcag 300ctgtccaaca tgatcgtgcg ctcctgcaag tgcagc 336<210>76<211>112<212>PRT<213>智人(Homo sapiens)<400>76Ala Leu Asp Thr Asn Tyr Cys Phe Ser Ser Thr Glu Lys Asn Cys Cys1 5 10 15Val Arg Gln Leu Tyr Ile Asp Phe Arg Lys Asp Leu Gly Trp Lys Trp20 25 30Ile His Glu Pro Lys Gly Tyr His Ala Asn Phe Cys Leu Gly Pro Cys35 40 45Pro Tyr Ile Trp Ser Leu Asp Thr Gln Tyr Ser Lys Val Leu Ala Leu50 55 60Tyr Asn Gln His Asn Pro Gly Ala Ser Ala Ala Pro Cys Cys Val Pro65 70 75 80Gln Ala Leu Glu Pro Leu Pro Ile Val Tyr Tyr Val Gly Arg Lys Pro85 90 95Lys Val Glu Gln Leu Ser Asn Met Ile Val Arg Ser Cys Lys Cys Ser100 105 110<210>77<211>1695<212>DNA<213>智人(Homo sapiens)<400>77caagcaggat acgtttttct gttgggcatt gactagattg tttgcaaaag tttcgcatca 60aaaacaaaca acaacaacaa aaaaccaaac aactctcctt gatctatact ttgagaattg120ttgatttctt tttttttatt ctgactttta aaaacaactt ttttttccac ttttttaaaa180aatgcactac tgtgtgctga gcgcttttct gatcctgcat ctggtcacgg tcgcgctcag240cctgtctacc tgcagcacac tcgatatgga ccagttcatg cgcaagagga tcgaggcgat300ccgcgggcag atcctgagca agctgaagct caccagtccc ccagaagact atcctgagcc360cgaggaagtc cccccggagg tgatttccat ctacaacagc accagggact tgctccagga420gaaggcgagc cggagggcgg ccgcctgcga gcgcgagagg agcgacgaag agtactacgc480caaggaggtt tacaaaatag acatgccgcc cttcttcccc tccgaaaatg ccatcccgcc540cactttctac agaccctact tcagaattgt tcgatttgac gtctcagcaa tggagaagaa600tgcttccaat ttggtgaaag cagagttcag agtctttcgt ttgcagaacc caaaagccag660agtgcctgaa caacggattg agctatatca gattctcaag tccaaagatt taacatctcc720aacccagcgc tacatcgaca gcaaagttgt gaaaacaaga gcagaaggcg aatggctctc780cttcgatgta actgatgctg ttcatgaatg gcttcaccat aaagacagga acctgggatt840
taaaataagc ttacactgtc cctgctgcac ttttgtacca tctaataatt acatcatccc 900aaataaaagt gaagaactag aagcaagatt tgcaggtatt gatggcacct ccacatatac 960cagtggtgat cagaaaacta taaagtccac taggaaaaaa aacagtggga agaccccaca 1020tctcctgcta atgttattgc cctcctacag acttgagtca caacagacca accggcggaa 1080gaagcgtgct ttggatgcgg cctattgctt tagaaatgtg caggataatt gctgcctacg 1140tccactttac attgatttca agagggatct agggtggaaa tggatacacg aacccaaagg 1200gtacaatgcc aacttctgtg ctggagcatg cccgtattta tggagttcag acactcagca 1260cagcagggtc ctgagcttat ataataccat aaatccagaa gcatctgctt ctccttgctg 1320cgtgtcccaa gatttagaac ctctaaccat tctctactac attggcaaaa cacccaagat 1380tgaacagctt tctaatatga ttgtaaagtc ttgcaaatgc agctaaaatt cttggaaaag 1440tggcaagacc aaaatgacaa tgatgatgat aatgatgatg acgacgacaa cgatgatgct 1500tgtaacaaga aaacataaga gagccttggt tcatcagtgt taaaaaattt ttgaaaaggc 1560ggtactagtt cagacacttt ggaagtttgt gttctgtttg ttaaaactgg catctgacac 1620aaaaaaagtt gaaggcctta ttctacattt cacctacttt gtaagtgaga gagacaagaa 1680gcaaattttt ttaaa 1695<210>78<211>414<212>PRT<213>智人(Homo sapiens)<400>78Met His Tyr Cys Val Leu Ser Ala Phe Leu Ile Leu His Leu Val Thr1 5 10 15Val Ala Leu Ser Leu Ser Thr Cys Ser Thr Leu Asp Met Asp Gln Phe20 25 30Met Arg Lys Arg Ile Glu Ala Ile Arg Gly Gln Ile Leu Ser Lys Leu35 40 45Lys Leu Thr Ser Pro Pro Glu Asp Tyr Pro Glu Pro Glu Glu Val Pro50 55 60Pro Glu Val Ile Ser Ile Tyr Asn Ser Thr Arg Asp Leu Leu Gln Glu65 70 75 80Lys Ala Ser Arg Arg Ala Ala Ala Cys Glu Arg Glu Arg Ser Asp Glu85 90 95Glu Tyr Tyr Ala Lys Glu Val Tyr Lys Ile Asp Met Pro Pro Phe Phe100 105 110Pro Ser Glu Asn Ala Ile Pro Pro Thr Phe Tyr Arg Pro Tyr Phe Arg115 120 125Ile Val Arg Phe Asp Val Ser Ala Met Glu Lys Asn Ala Ser Asn Leu130 135 140Val Lys Ala Glu Phe Arg Val Phe Arg Leu Gln Asn Pro Lys Ala Arg145 150 155 160
Val Pro Glu Gln Arg Ile Glu Leu Tyr Gln Ile Leu Lys Ser Lys Asp165 170 175Leu Thr Ser Pro Thr Gln Arg Tyr Ile Asp Ser Lys Val Val Lys Thr180 185 190Arg Ala Glu Gly Glu Trp Leu Ser Phe Asp Val Thr Asp Ala Val His195 200 205Glu Trp Leu His His Lys Asp Arg Asn Leu Gly Phe Lys Ile Ser Leu210 215 220His Cys Pro Cys Cys Thr Phe Val Pro Ser Asn Asn Tyr Ile Ile Pro225 230 235 240Ash Lys Ser Glu Glu Leu Glu Ala Arg Phe Ala Gly Ile Asp Gly Thr245 250 255Ser Thr Tyr Thr Ser Gly Asp Gln Lys Thr Ile Lys Ser Thr Arg Lys260 265 270Lys Asn Ser Gly Lys Thr Pro His Leu Leu Leu Met Leu Leu Pro Ser275 280 285Tyr Arg Leu Glu Ser Gln Gln Thr Asn Arg Arg Lys Lys Arg Ala Leu290 295 300Asp Ala Ala Tyr Cys Phe Arg Asn Val Gln Asp Asn Cys Cys Leu Arg305 310 315 320Pro Leu Tyr Ile Asp Phe Lys Arg Asp Leu Gly Trp Lys Trp Ile His325 330 335Glu Pro Lys Gly Tyr Asn Ala Asn Phe Cys Ala Gly Ala Cys Pro Tyr340 345 350Leu Trp Ser Ser Asp Thr Gln His Ser Arg Val Leu Ser Leu Tyr Asn355 360 365Thr Ile Asn Pro Glu Ala Ser Ala Ser Pro Cys Cys Val Ser Gln Asp370 375 380Leu Glu Pro Leu Thr Ile Leu Tyr Tyr Ile Gly Lys Thr Pro Lys Ile385 390 395 400Glu Gln Leu Ser Asn Met Ile Val Lys Ser Cys Lys Cys Ser405 410<210>79<211>336<212>DNA<213>智人(Homo sapiens)
<400>79gctttggatg cggcctattg ctttagaaat gtgcaggata attgctgcct acgtccactt 60tacattgatt tcaagaggga tctagggtgg aaatggatac acgaacccaa agggtacaat120gccaacttct gtgctggagc atgcccgtat ttatggagtt cagacactca gcacagcagg180gtcctgagct tatataatac cataaatcca gaagcatctg cttctccttg ctgcgtgtcc240caagatttag aacctctaac cattctctac tacattggca aaacacccaa gattgaacag300ctttctaata tgattgtaaa gtcttgcaaa tgcagc 336<210>80<211>112<212>PRT<213>智人(Homo sapiens)<400>80Ala Leu Asp Ala Ala Tyr Cys Phe Arg Asn Val Gln Asp Asn Cys Cys1 5 10 15Leu Arg Pro Leu Tyr Ile Asp Phe Lys Arg Asp Leu Gly Trp Lys Trp20 25 30Ile His Glu Pro Lys Gly Tyr Asn Ala Asn Phe Cys Ala Gly Ala Cys35 40 45Pro Tyr Leu Trp Ser Ser Asp Thr Gln His Ser Arg Val Leu Ser Leu50 55 60Tyr Asn Thr Ile Asn Pro Glu Ala Ser Ala Ser Pro Cys Cys Val Ser65 70 75 80Gln Asp Leu Glu Pro Leu Thr Ile Leu Tyr Tyr Ile Gly Lys Thr Pro85 90 95Lys Ile Glu Gln Leu Ser Asn Met Ile Val Lys Ser Cys Lys Cys Ser100 105 110<210>81<211>2574<212>DNA<213>智人(Homo sapiens)<400>81cctgtttaga cacatggaca acaatcccag cgctacaagg cacacagtcc gcttcttcgt 60cctcagggtt gccagcgctt cctggaagtc ctgaagctct cgcagtgcag tgagttcatg120caccttcttg ccaagcctca gtctttggga tctggggagg ccgcctggtt ttcctccctc180cttctgcacg tctgctgggg tctcttcctc tccaggcctt gccgtccccc tggcctctct240tcccagctca cacatgaaga tgcacttgca aagggctctg gtggtcctgg ccctgctgaa300ctttgccacg gtcagcctct ctctgtccac ttgcaccacc ttggacttcg gccacatcaa360gaagaagagg gtggaagcca ttaggggaca gatcttgagc aagctcaggc tcaccagccc420ccctgagcca acggtgatga cccacgtccc ctatcaggtc ctggcccttt acaacagcac480ccgggagctg ctggaggaga tgcatgggga gagggaggaa ggctgcaccc aggaaaacac540cgagtcggaa tactatgcca aagaaatcca taaattcgac atgatccagg ggctggcgga600
gcacaacgaa ctggctgtct gccctaaagg aattacctcc aaggttttcc gcttcaatgt 660gtcctcagtg gagaaaaata gaaccaacct attccgagca gaattccggg tcttgcgggt 720gcccaacccc agctctaagc ggaatgagca gaggatcgag ctcttccaga tccttcggcc 780agatgagcac attgccaaac agcgctatat cggtggcaag aatctgccca cacggggcac 840tgccgagtgg ctgtcctttg atgtcactga cactgtgcgt gagtggctgt tgagaagaga 900gtccaactta ggtctagaaa tcagcattca ctgtccatgt cacacctttc agcccaatgg 960agatatcctg gaaaacattc acgaggtgat ggaaatcaaa ttcaaaggcg tggacaatga 1020ggatgaccat ggccgtggag atctggggcg cctcaagaag cagaaggatc accacaaccc 1080tcatctaatc ctcatgatga ttcccccaca ccggctcgac aacccgggcc aggggggtca 1140gaggaagaag cgggctttgg acaccaatta ctgcttccgc aacttggagg agaactgctg 1200tgtgcgcccc ctctacattg acttccgaca ggatctgggc tggaagtggg tccatgaacc 1260taagggctac tatgccaact tctgctcagg cccttgccca tacctccgca gtgcagacac 1320aacccacagc acggtgctgg gactgtacaa cactctgaac cctgaagcat ctgcctcgcc 1380ttgctgcgtg ccccaggacc tggagcccct gaccatcctg tactatgttg ggaggacccc 1440caaagtggag cagctctcca acatggtggt gaagtcttgt aaatgtagct gagaccccac 1500gtgcgacaga gagaggggag agagaaccac cactgcctga ctgcccgctc ctcgggaaac 1560acacaagcaa caaacctcac tgagaggcct ggagcccaca accttcggct ccgggcaaat 1620ggctgagatg gaggtttcct tttggaacat ttctttcttg ctggctctga gaatcacggt 1680ggtaaagaaa gtgtgggttt ggttagagga aggctgaact cttcagaaca cacagacttt 1740ctgtgacgca gacagagggg atggggatag aggaaaggga tggtaagttg agatgttgtg 1800tggcaatggg atttgggcta ccctaaaggg agaaggaagg gcagagaatg gctgggtcag 1860ggccagactg gaagacactt cagatctgag gttggatttg ctcattgctg taccacatct 1920gctctaggga atctggatta tgttatacaa ggcaagcatt ttttttttta aagacaggtt 1980acgaagacaa agtcccagaa ttgtatctca tactgtctgg gattaagggc aaatctatta 2040cttttgcaaa ctgtcctcta catcaattaa catcgtgggt cactacaggg agaaaatcca 2100ggtcatgcag ttcctggccc atcaactgta ttgggccttt tggatatgct gaacgcagaa 2160gaaagggtgg aaatcaaccc tctcctgtct gccctctggg tccctcctct cacctctccc 2220tcgatcatat ttccccttgg acacttggtt agacgccttc caggtcagga tgcacatttc 2280tggattgtgg ttccatgcag ccttggggca ttatgggtct tcccccactt cccctccaag 2340accctgtgtt catttggtgt tcctggaagc aggtgctaca acatgtgagg cattcgggga 2400agctgcacat gtgccacaca gtgacttggc cccagacgca tagactgagg tataaagaca 2460agtatgaata ttactctcaa aatctttgta taaataaata tttttggggc atcctggatg 2520atttcatctt ctggaatatt gtttctagaa cagtaaaagc cttattctaa ggtg2574<210>82<21l>412<212>PRT<213>智人(Homo sapiens)<400>82Met Lys Met His Leu Gln Arg Ala Leu Val Val Leu Ala Leu Leu Asn1 5 10 15Phe Ala Thr Val Ser Leu Ser Leu Ser Thr Cys Thr Thr Leu Asp Phe20 25 30Gly His Ile Lys Lys Lys Arg Val Glu Ala Ile Arg Gly Gln Ile Leu35 40 45Ser Lys Leu Arg Leu Thr Ser Pro Pro Glu Pro Thr Val Met Thr His50 55 60
Val Pro Tyr Gln Val Leu Ala Leu Tyr Asn Ser Thr Arg Glu Leu Leu65 70 75 80Glu Glu Met His Gly Glu Arg Glu Glu Gly Cys Thr Gln Glu Asn Thr85 90 95Glu Ser Glu Tyr Tyr Ala Lys Glu Ile His Lys Phe Asp Met Ile Gln100 105 110Gly Leu Ala Glu His Asn Glu Leu Ala Val Cys Pro Lys Gly Ile Thr115 120 125Ser Lys Val Phe Arg Phe Asn Val Ser Ser Val Glu Lys Asn Arg Thr130 135 140Asn Leu Phe Arg Ala Glu Phe Arg Val Leu Arg Val Pro Asn Pro Ser145 150 155 160Ser Lys Arg Asn Glu Gln Arg Ile Glu Leu Phe Gln Ile Leu Arg Pro165 170 175Asp Glu His Ile Ala Lys Gln Arg Tyr Ile Gly Gly Lys Asn Leu Pro180 185 190Thr Arg Gly Thr Ala Glu Trp Leu Ser Phe Asp Val Thr Asp Thr Val195 200 205Arg Glu Trp Leu Leu Arg Arg Glu Ser Asn Leu Gly Leu Glu Ile Ser210 215 220Ile His Cys Pro Cys His Thr Phe Gln Pro Asn Gly Asp Ile Leu Glu225 230 235 240Asn Ile His Glu Val Met Glu Ile Lys Phe Lys Gly Val Asp Asn Glu245 250 255Asp Asp His Gly Arg Gly Asp Leu Gly Arg Leu Lys Lys Gln Lys Asp260 265 270His His Asn Pro His Leu Ile Leu Met Met Ile Pro Pro His Arg Leu275 280 285Asp Asn Pro Gly Gln Gly Gly Gln Arg Lys Lys Arg Ala Leu Asp Thr290 295 300Asn Tyr Cys Phe Arg Asn Leu Glu Glu Asn Cys Cys Val Arg Pro Leu305 310 315 320Tyr Ile Asp Phe Arg Gln Asp Leu Gly Trp Lys Trp Val His Glu Pro325 330 335Lys Gly Tyr Tyr Ala Asn Phe Cys Ser Gly Pro Cys Pro Tyr Leu Arg
340 345 350Ser Ala Asp Thr Thr His Ser Thr Val Leu Gly Leu Tyr Asn Thr Leu355 360 365Asn Pro Glu Ala Ser Ala Ser Pro Cys Cys Val Pro Gln Asp Leu Glu370 375 380Pro Leu Thr Ile Leu Tyr Tyr Val Gly Arg Thr Pro Lys Val Glu Gln385 390 395 400Leu Ser Asn Met Val Val Lys Ser Cys Lys Cys Ser405 410<210>83<211>3213<212>DNA<213>智人(Homo sapiens)<400>83agagactcaa gatgattccc tttttaccca tgttttctct actattgctg cttattgtta 60accctataaa cgccaacaat cattatgaca agatcttggc tcatagtcgt atcaggggtc120gggaccaagg cccaaatgtc tgtgcccttc aacagatttt gggcaccaaa aagaaatact180tcagcacttg taagaactgg tataaaaagt ccatctgtgg acagaaaacg actgttttat240atgaatgttg ccctggttat atgagaatgg aaggaatgaa aggctgccca gcagttttgc300ccattgacca tgtttatggc actctgggca tcgtgggagc caccacaacg cagcgctatt360ctgacgcctc aaaactgagg gaggagatcg agggaaaggg atccttcact tactttgcac420cgagtaatga ggcttgggac aacttggatt ctgatatccg tagaggtttg gagagcaacg480tgaatgttga attactgaat gctttacata gtcacatgat taataagaga atgttgacca540aggacttaaa aaatggcatg attattcctt caatgtataa caatttgggg cttttcatta600accattatcc taatggggtt gtcactgtta attgtgctcg aatcatccat gggaaccaga660ttgcaacaaa tggtgttgtc catgtcattg accgtgtgct tacacaaatt ggtacctcaa720ttcaagactt cattgaagca gaagatgacc tttcatcttt tagagcagct gccatcacat780cggacatatt ggaggccctt ggaagagacg gtcacttcac actctttgct cccaccaatg840aggcttttga gaaacttcca cgaggtgtcc tagaaaggtt catgggagac aaagtggctt900ccgaagctct tatgaagtac cacatcttaa atactctcca gtgttctgag tctattatgg960gaggagcagt ctttgagacg ctggaaggaa atacaattga gataggatgt gacggtgaca 1020gtataacagt aaatggaatc aaaatggtga acaaaaagga tattgtgaca aataatggtg 1080tgatccattt gattgatcag gtcctaattc ctgattctgc caaacaagtt attgagctgg 1140ctggaaaaca gcaaaccacc ttcacggatc ttgtggccca attaggcttg gcatctgctc 1200tgaggccaga tggagaatac actttgctgg cacctgtgaa taatgcattt tctgatgata 1260ctctcagcat ggttcagcgc ctccttaaat taattctgca gaatcacata ttgaaagtaa 1320aagttggcct taatgagctt tacaacgggc aaatactgga aaccatcgga ggcaaacagc 1380tcagagtctt cgtatatcgt acagctgtct gcattgaaaa ttcatgcatg gagaaaggga 1440gtaagcaagg gagaaacggt gcgattcaca tattccgcga gatcatcaag ccagcagaga 1500aatccctcca tgaaaagtta aaacaagata agcgctttag caccttcctc agcctacttg 1560aagctgcaga cttgaaagag ctcctgacac aacctggaga ctggacatta tttgtgccaa 1620ccaatgatgc ttttaaggga atgactagtg aagaaaaaga aattctgata cgggacaaaa 1680atgctcttca aaacatcatt ctttatcacc tgacaccagg agttttcatt ggaaaaggat 1740ttgaacctgg tgttactaac attttaaaga ccacacaagg aagcaaaatc tttctgaaag 1800aagtaaatga tacacttctg gtgaatgaat tgaaatcaaa agaatctgac atcatgacaa 1860caaatggtgt aattcatgtt gtagataaac tcctctatcc agcagacaca cctgttggaa 1920
atgatcaact gctggaaata cttaataaat taatcaaata catccaaatt aagtttgttc 1980gtggtagcac cttcaaagaa atccccgtga ctgtctatac aactaaaatt ataaccaaag 2040ttgtggaacc aaaaattaaa gtgattgaag gcagtcttca gcctattatc aaaactgaag 2100gacccacact aacaaaagtc aaaattgaag gtgaacctga attcagactg attaaagaag 2160gtgaaacaat aactgaagtg atccatggag agccaattat taaaaaatac accaaaatca 2220ttgatggagt gcctgtggaa ataactgaaa aagagacacg agaagaacga atcattacag 2280gtcctgaaat aaaatacact aggatttcta ctggaggtgg agaaacagaa gaaactctga 2340agaaattgtt acaagaagag gtcaccaagg tcaccaaatt cattgaaggt ggtgatggtc 2400atttatttga agatgaagaa attaaaagac tgcttcaggg agacacaccc gtgaggaagt 2460tgcaagccaa caaaaaagtt caaggttcta gaagacgatt aagggaaggt cgttctcagt 2520gaaaatccaa aaaccagaaa aaaatgttta tacaacccta agtcaataac ctgaccttag 2580aaaattgtga gagccaagtt gacttcagga actgaaacat cagcacaaag aagcaatcat 2640caaataattc tgaacacaaa tttaatattt ttttttctga atgagaaaca tgagggaaat 2700tgtggagtta gcctcctgtg gtaaaggaat tgaagaaaat ataacacctt acaccctttt 2760tcatcttgac attaaaagtt ctggctaact ttggaatcca ttagagaaaa atccttgtca 2820ccagattcat tacaattcaa atcgaagagt tgtgaactgt tatcccattg aaaagaccga 2880gccttgtatg tatgttatgg atacataaaa tgcacgcaag ccattatctc tccatgggaa 2940gctaagttat aaaaataggt gcttggtgta caaaactttt tatatcaaaa ggctttgcac 3000atttctatat gagtgggttt actggtaaat tatgttattt tttacaacta attttgtact 3060ctcagaatgt ttgtcatatg cttcttgcaa tgcatatttt ttaatctcaa acgtttcaat 3120aaaaccattt ttcagatata aagagaatta cttcaaattg agtaattcag aaaaactcaa 3180gatttaagtt aaaaagtggt ttggacttgg gaa 3213<210>84<211>836<212>PRT<213>智人(Homo sapiens)<400>84Met Ile Pro Phe Leu Pro Met Phe Ser Leu Leu Leu Leu Leu Ile Val1 5 10 15Asn Pro Ile Asn Ala Asn Asn His Tyr Asp Lys Ile Leu Ala His Ser20 25 30Arg Ile Arg Gly Arg Asp Gln Gly Pro Asn Val Cys Ala Leu Gln Gln35 40 45Ile Leu Gly Thr Lys Lys Lys Tyr Phe Ser Thr Cys Lys Asn Trp Tyr50 55 60Lys Lys Ser Ile Cys Gly Gln Lys Thr Thr Val Leu Tyr Glu Cys Cys65 70 75 80Pro Gly Tyr Met Arg Met Glu Gly Met Lys Gly Cys Pro Ala Val Leu85 90 95Pro Ile Asp His Val Tyr Gly Thr Leu Gly Ile Val Gly Ala Thr Thr100 105 110Thr Gln Arg Tyr Ser Asp Ala Ser Lys Leu Arg Glu Glu Ile Glu Gly115 120 125
Lys Gly Ser Phe Thr Tyr Phe Ala Pro Ser Asn Glu Ala Trp Asp Asn130 135 140Leu Asp Ser Asp Ile Arg Arg Gly Leu Glu Ser Asn Val Asn Val Glu145 150 155 160Leu Leu Asn Ala Leu His Ser His Met Ile Asn Lys Arg Met Leu Thr165 170 175Lys Asp Leu Lys Asn Gly Met Ile Ile Pro Ser Met Tyr Asn Asn Leu180 185 190Gly Leu Phe Ile Asn His Tyr Pro Asn Gly Val Val Thr Val Asn Cys195 200 205Ala Arg Ile Ile His Gly Asn Gln Ile Ala Thr Asn Gly Val Val His210 215 220Val Ile Asp Arg Val Leu Thr Gln Ile Gly Thr Ser Ile Gln Asp Phe225 230 235 240Ile Glu Ala Glu Asp Asp Leu Ser Ser Phe Arg Ala Ala Ala Ile Thr245 250 255Ser Asp Ile Leu Glu Ala Leu Gly Arg Asp Gly His Phe Thr Leu Phe260 265 270Ala Pro Thr Asn Glu Ala Phe Glu Lys Leu Pro Arg Gly Val Leu Glu275 280 285Arg Phe Met Gly Asp Lys Val Ala Ser Glu Ala Leu Met Lys Tyr His290 295 300Ile Leu Asn Thr Leu Gln Cys Ser Glu Ser Ile Met Gly Gly Ala Val305 310 315 320Phe Glu Thr Leu Glu Gly Asn Thr Ile Glu Ile Gly Cys Asp Gly Asp325 330 335Ser Ile Thr Val Asn Gly Ile Lys Met Val Asn Lys Lys Asp Ile Val340 345 350Thr Asn Asn Gly Val Ile His Leu Ile Asp Gln Val Leu Ile Pro Asp355 360 365Ser Ala Lys Gln Val Ile Glu Leu Ala Gly Lys Gln Gln Thr Thr Phe370 375 380Thr Asp Leu Val Ala Gln Leu Gly Leu Ala Ser Ala Leu Arg Pro Asp385 390 395 400
Gly Glu Tyr Thr Leu Leu Ala Pro Val Asn Asn Ala Phe Ser Asp Asp405 410 415Thr Leu Ser Met Val Gln Arg Leu Leu Lys Leu Ile Leu Gln Asn His420 425 430Ile Leu Lys Val Lys Val Gly Leu Asn Glu Leu Tyr Asn Gly Gln Ile435 440 445Leu Glu Thr Ile Gly Gly Lys Gln Leu Arg Val Phe Val Tyr Arg Thr450 455 460Ala Val Cys Ile Glu Asn Ser Cys Met Glu Lys Gly Ser Lys Gln Gly465 470 475 480Arg Asn Gly Ala Ile His Ile Phe Arg Glu Ile Ile Lys Pro Ala Glu485 490 495Lys Ser Leu His Glu Lys Leu Lys Gln Asp Lys Arg Phe Ser Thr Phe500 505 510Leu Ser Leu Leu Glu Ala Ala Asp Leu Lys Glu Leu Leu Thr Gln Pro515 520 525Gly Asp Trp Thr Leu Phe Val Pro Thr Asn Asp Ala Phe Lys Gly Met530 535 540Thr Ser Glu Glu Lys Glu Ile Leu Ile Arg Asp Lys Asn Ala Leu Gln545 550 555 560Asn Ile Ile Leu Tyr His Leu Thr Pro Gly Val Phe Ile Gly Lys Gly565 570 575Phe Glu Pro Gly Val Thr Asn Ile Leu Lys Thr Thr Gln Gly Ser Lys580 585 590Ile Phe Leu Lys Glu Val Asn Asp Thr Leu Leu Val Asn Glu Leu Lys595 600 605Ser Lys Glu Ser Asp Ile Met Thr Thr Asn Gly Val Ile His Val Val610 615 620Asp Lys Leu Leu Tyr Pro Ala Asp Thr Pro Val Gly Asn Asp Gln Leu625 630 635 640Leu Glu Ile Leu Asn Lys Leu Ile Lys Tyr Ile Gln Ile Lys Phe Val645 650 655Arg Gly Ser Thr Phe Lys Glu Ile Pro Val Thr Val Tyr Thr Thr Lys660 665 670Ile Ile Thr Lys Val Val Glu Pro Lys Ile Lys Val Ile Glu Gly Ser
675 680 685Leu Gln Pro Ile Ile Lys Thr Glu Gly Pro Thr Leu Thr Lys Val Lys690 695 700Ile Glu Gly Glu Pro Glu Phe Arg Leu Ile Lys Glu Gly Glu Thr Ile705 710 715 720Thr Glu Val Ile His Gly Glu Pro Ile Ile Lys Lys Tyr Thr Lys Ile725 730 735Ile Asp Gly Val Pro Val Glu Ile Thr Glu Lys Glu Thr Arg Glu Glu740 745 750Arg Ile Ile Thr Gly Pro Glu Ile Lys Tyr Thr Arg Ile Ser Thr Gly755 760 765Gly Gly Glu Thr Glu Glu Thr Leu Lys Lys Leu Leu Gln Glu Glu Val770 775 780Thr Lys Val Thr Lys Phe Ile Glu Gly Gly Asp Gly His Leu Phe Glu785 790 795 800Asp Glu Glu Ile Lys Arg Leu Leu Gln Gly Asp Thr Pro Val Arg Lys805 810 815Leu Gln Ala Asn Lys Lys Val Gln Gly Ser Arg Arg Arg Leu Arg Glu820 825 830Gly Arg Ser Gln83权利要求
1.一种多层聚合物包裹物，它包括至少两个可生物降解的聚合物片层，其中，所述至少两个可生物降解的聚合物片层相互结合，所述多层聚合物包裹物还包含至少一种成骨诱导性制剂。
2.如权利要求1所述的多层聚合物包裹物，其特征在于，所述至少一种成骨诱导性制剂包含在至少一个可生物降解的聚合物片层中。
3.如权利要求1所述的多层聚合物包裹物，其特征在于，所述至少一种成骨诱导性制剂包含在至少两个可生物降解的聚合物片层之间。
4.如权利要求1所述的多层聚合物包裹物，其特征在于，所述成骨诱导性制剂还包含一种或多种成骨诱导剂。
5.如权利要求4所述的多层聚合物包裹物，其特征在于，所述一种或多种成骨诱导剂包括BMP-2。
6.如权利要求4所述的多层聚合物包裹物，其特征在于，所述一种或多种成骨诱导剂选自BMP-1、BMP-2、BMP-3、BMP-4、BMP-5、BMP-6、BMP-7、BMP-8、BMP-9、BMP-10、BMP-11、BMP-12、BMP-13、BMP-15、BMP-16、BMP-17、BMP-18或其任意组合。
7.如权利要求4所述的多层聚合物包裹物，其特征在于，所述一种或多种成骨诱导剂选自CTGF-1、CTGF-2、CGTF-3、CTGF-4或其任意组合。
8.如权利要求4所述的多层聚合物包裹物，其特征在于，所述一种或多种成骨诱导剂选自VEGF-A、VEGF-B、VEGF-C、VEGF-D、VEGF-E或其任意组合。
9.如权利要求4所述的多层聚合物包裹物，其特征在于，所述一种或多种成骨诱导剂是护骨蛋白。
10.如权利要求4所述的多层聚合物包裹物，其特征在于，所述一种或多种成骨诱导剂选自TGF-β-1、TGF-β-2、TGF-β-3或其任意组合。
11.如权利要求4所述的多层聚合物包裹物，其特征在于，所述一种或多种成骨诱导剂选自一种或多种BMP、一种或多种VEGF、一种或多种CTGF、护骨蛋白、一种或多种TGF-β或其任意组合。
12.如权利要求4所述的多层聚合物包裹物，其特征在于，所述一种或多种成骨诱导剂以治疗性多核苷酸的形式提供。
13.如权利要求4所述的多层聚合物包裹物，其特征在于，所述一种或多种成骨诱导剂以治疗性多肽的形式提供。
14.如权利要求13所述的多层聚合物包裹物，其特征在于，所述治疗性多肽以成熟多肽的形式给予。
15.如权利要求1所述的多层聚合物包裹物，其特征在于，所述成骨诱导性制剂包括缓释制剂。
16.如权利要求4所述的多层聚合物包裹物，其特征在于，所述成骨诱导性制剂还包含一种或多种抗生素。
17.如权利要求4所述的多层聚合物包裹物，其特征在于，所述成骨诱导性制剂还包含脱矿物质骨基质。
18.如权利要求4所述的多层聚合物包裹物，其特征在于，所述成骨诱导性制剂还包含骨髓抽吸物。
19.如权利要求4所述的多层聚合物包裹物，其特征在于，所述成骨诱导性制剂还包含骨髓浓缩物。
20.如权利要求4所述的多层聚合物包裹物，其特征在于，所述成骨诱导性制剂还包含一种或多种免疫抑制剂。
21.如权利要求4所述的多层聚合物包裹物，其特征在于，所述成骨诱导性制剂还包含载体。
22.如权利要求21所述的多层聚合物包裹物，其特征在于，所述载体是胶原。
23.如权利要求22所述的多层聚合物包裹物，其特征在于，所述胶原是重组产生的胶原。
24.一种成套工具，它包括含有成骨诱导剂的用于植入的多层聚合物包裹物。
25.如权利要求24所述的成套工具，其特征在于，所述多层聚合物包裹物包含成骨诱导性制剂。
26.如权利要求1所述的多层聚合物包裹物，其特征在于，所述至少两个可生物降解的聚合物片层各自包含含有至少一种成骨诱导剂的至少一种成骨诱导性制剂。
27.如权利要求26所述的多层聚合物包裹物，其特征在于，所述至少两个可生物降解的聚合物片层在成骨诱导性制剂中包含至少一种不同的成骨诱导剂。
28.如权利要求26所述的多层聚合物包裹物，其特征在于，所述至少两个可生物降解的聚合物片层在成骨诱导性制剂中包含不同浓度的至少一种成骨诱导剂。
29.一种包含至少一个可生物降解的聚合物片层的聚合物包裹物，其中，所述至少一个可生物降解的聚合物片层还包含至少一种成熟BMP多肽和至少一种成熟护骨蛋白多肽。
30.一种包含至少一个可生物降解的聚合物片层的聚合物包裹物，其中，所述至少一个可生物降解的聚合物片层还包含至少一种编码成熟BMP多肽的多核苷酸和至少一种编码成熟护骨蛋白多肽的多核苷酸。
全文摘要
本申请描述了一种包含一种或多种成骨诱导性制剂的聚合物包裹物，其中，所述成骨诱导性制剂各自包含一种或多种成骨诱导剂。在一个实施方式中，成骨诱导性制剂包含在可生物降解的聚合物片层中。在本发明另一个实施方式中，聚合物包裹物包括至少两个或多个独立的可生物降解聚合物片层或层，其任选地包含含有至少一种成骨诱导剂的成骨诱导性制剂。成骨诱导性制剂可以是速释或缓释制剂。该方法还涉及预防和治疗植入矫形外科装置或其它植入物后形成的溶骨性病变。
文档编号A61L27/54GK101068509SQ200580036296
公开日2007年11月7日 申请日期2005年8月31日 优先权日2004年9月1日
发明者J·C·塞尔布赛克 申请人:华沙整形外科股份有限公司