CN1420929A - 非内源性组成型活化的已知g蛋白偶联受体 - Google Patents
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Abstract
本专利申请文件所公开的发明涉及跨膜受体,具体地讲,涉及其内源配体已知的人G蛋白偶联受体(“已知GPCRs”),更具体地是涉及用于筛选实验的已知GPCRs的突变(非内源)形式,最优选所述筛选实验用于直接识别作为反激动剂,激动剂和部分激动剂的候选化合物。
Description
本专利申请要求了2000年4月7日美国专利和商标局受理的美国临时申请号US60/195747的优先权;本专利申请涉及1998年10月13日美国专利和商标局序列号为US09/170496的专利申请,各在此全文引用作为参考。发明领域
本专利申请文件所公开的发明涉及跨膜受体,具体地讲,涉及内源配体已被鉴定的人G蛋白偶联的受体(“已知的GPCR”),特别涉及已被改变从而具有或增强受体的组成型活性的已知GPCR。优选将该被改变的GPCR用于直接识别有可能作为受体激动剂、反激动剂或部分激动剂而用做治疗剂的候选化合物。发明背景
尽管在人体内有很多种类的受体,但到目前为止最丰富和最与治疗有关的是G蛋白偶联受体(GPCR或GPCRs)。据估计,在人类基因组内有大约100,000个基因,它们中的大约2%即2000个基因被估计用来编码GPCRs。包括GPCRs在内,其内源配体已被认识的受体被称为“已知”受体,内源配体尚不知晓的受体被称为“孤儿”受体。GPCRs代表着药物产品开发的一个重要领域:60%的处方药物开发自100个已知GPCRs中的大约20个。
GPCRs都具有一个相同的基元(motif)。所有这些受体具有七个由22到24个疏水氨基酸组成的序列,它们组成七个α螺旋,每个α螺旋都跨过膜(每个跨度都以数字表示,例如,跨膜-1(TM-1)、跨膜-2(TM-2)等)。跨膜螺旋通过氨基酸链连接,在细胞膜的外部即“细胞外”一边的氨基酸链在跨膜-2和跨膜-3、跨膜-4和跨膜-5、跨膜-6和跨膜-7之间(这些分别被称为“细胞外”区1、2和3(EC-1、EC-2和EC-3))。在细胞膜内部即“细胞内”一边,跨膜螺旋也通过氨基酸链进行连接,这些氨基酸链分别在跨膜-1和跨膜-2、跨膜-3和跨膜-4、跨膜-5和跨膜-6之间(这些分别被称为“细胞内”区1、2和3(IC-1、IC-2和IC-3))。受体的“羧基”(“C”)端是在细胞内的区域,受体的“氨基”(“N”)端在细胞外的区域。
一般来说,当内源配体与受体结合时(经常被称为受体的“活化”),细胞内区域的构象发生变化,以容许细胞内区域和细胞内“G-蛋白”进行偶联。据报道,GPCR对于G蛋白而言是“混杂的”,也就是说,GPCR可与不只一个G蛋白相互作用。参见,Kenakin,T.,43,生命科学(Life Sciences)1095(1988)。尽管存在其他G蛋白,但当前已被识别的G蛋白是Gq、Gs、Gi和Go。内源配体活化的GPCR与G-蛋白的偶联引发一个信号级联过程(被称为“信号传导”)。在通常情形下,信号传导最终导致细胞活化或细胞抑制。据认为,受体的IC-3环与羧基端都和G蛋白相互作用。
在生理条件下,GPCR存在于细胞膜上,并在“非活化”状态和“活化”状态这两种不同构象之间保持平衡。在非活性状态下的受体不能与细胞内信号传导途径相偶联以产生生物学反应。受体构象向活性状态的转变就使它与传导途径相偶联(通过G-蛋白)并产生生物学反应。
可通过内源配体或化合物如药物将受体稳定在其活性状态。近来的发现提供了除内源配体或药物之外能够促进和稳定受体到活性状态构象的方法,这包括但不限于对受体的氨基酸序列的修饰。这些方法通过模仿与受体结合的内源配体的作用来有效地稳定活性状态的受体。通过如此的配体非依赖性方法形成的稳定作用被称为“组成型受体活化”。
传统的配体依赖性筛选旨在通过非直接鉴定拮抗该配体对受体作用的化合物,以排除配体诱导的受体活化。但是这种化合物(有时被成为中性拮抗剂)通常不会影响受体不依赖配体的活性,或受体的过分活性,以及因这种过分活性所产生的异常细胞应答。由于传统的中性拮抗剂不封闭这些受体异常的不依赖配体的活性,从而这一点有关越来越多的一些疾病,如在下表所示的疾病,所述疾病与过分活性的GPCR有关联。
背景技术表1
发明概述
| 疾病 | 过分活性的GPCR |
| 精神分裂症 | 5-HT2A,D2 |
| 抑郁症 | 5-HT2A |
| 甲状腺功能亢进 | 促甲状腺素 |
| 哮喘 | 血管紧张肽AT1A |
| 黑素瘤 | 腺苷A1 |
| 色素性视网膜炎 | MC-1 |
| 色素性视网膜炎 | 视紫红质受体 |
这里公开的是内源性已知GPCR的非内源形式及其应用。附图说明
图1:提供了非内源TSHR-A623I(“信号增强子”)和一种内源靶受体共转染的比较性分析结果,在这一情况下利用腺苷酸环化酶实验,对GPR24(“GPR24wt”)和非内源性组成型活化的靶受体GPR24(“T255K”,“T255K/T257R”,“24-IC3-SST2”,“C305Y”,“P271L”,“W269C”,“W269F”,“W269L”,“F265I”,“I261Q”和“D140N”)这二者与非内源TSHR-A623I的共转染进行比较。该实验涉及添加TSH和MCH,其分别是TSHR和GPR24的内源配体。
图2:提供了利用腺苷酸环化酶实验对非内源信号增强子TSHR-A623I(有或无TSH)和非内源靶受体GPR5(“GPR5wt”)的共转染,与非内源组成型活化的靶受体GPR5(“V224K”)和非内源TSHR-A623I(有或无TSH)的共转染的比较性分析结果。
图3A-3E提供了利用8XCRE-Luc报道质粒,对CMV,非内源性组成型活化的GPCRs的比较所检测的信号结果的图示。
图4描述了几种非内源性GPC24与该受体的内源受体形式相比所产生的IP3。
图5图示了基于膜的环AMP分析的结果,其提供了TSHR-A263K:融合蛋白的组成型信号和一个对照载体(pCMV)的比较性结果。详细说明
本科学文献涉及受体并采用一些术语来描述对受体具有不同作用的配体。为了清楚和前后一致,在本发明文献中将由始至终使用下列定义。在这些定义与这些词语的其他定义冲突时,选择下列定义:
激动剂意味着激活细胞内反应的物质(例如,配体、候选化合物),此时它们结合受体或促进GTP与膜结合。
在此应用的氨基酸缩写列于下表:
表A
丙氨酸 ALA A
精氨酸 ARG R
天冬酰胺 ASN N
天冬氨酸 ASP D
半胱氨酸 CYS C
谷氨酸 GLU E
谷氨酰胺 GLN Q
甘氨酸 GLY G
组氨酸 HIS H
异亮氨酸 ILE I
亮氨酸 LEU L
赖氨酸 LYS K
蛋氨酸 MET M
苯丙氨酸 PHE F
脯氨酸 PRO P
丝氨酸 SER S
苏氨酸 THR T
色氨酸 TRP W
酪氨酸 TYR Y
缬氨酸 VAL V
部分激动剂意味着这样的物质(例如,配体、候选化合物),它们与受体结合时,激活细胞内反应或者促进GTP与膜结合的程度低于激动剂。
拮抗剂意味着这样的物质(例如,配体、候选化合物),它和激动剂在同一位点与受体竞争性地结合,但不激活由受体的活性形式引起的细胞内反应,并可因此抑制由激动剂或部分激动剂促进的细胞内反应。拮抗剂在没有激动剂或部分激动剂的情形下并不削弱基本细胞内反应。
候选化合物在本公开的发明中,指将经受筛选技术检验的小分子(例如但不限于化学化合物)。
组合物是指至少包含一种成分的材料;“药物组合物”即是组合物的一个例子。
化合物效应意味着化合物抑制或者刺激受体功能的能力的量度,它与受体结合亲和力相对。测定化合物效应的典型方法在本专利申请的实施例部分中进一步公开。
密码子是指三个一组的核苷酸(或与核苷酸相当的词),核苷酸通常由一个核苷(腺苷(A)、鸟苷(G)、胞苷(C)、尿苷(U)和胸苷(T))偶联一个磷酸酯基团组成,翻译时密码子编码氨基酸。
组成型活化的受体意味着易受组成型受体活化的受体。组成型活化的受体可以是内源的也可以是非内源的。
组成型受体活化意味着不利用它的内源配体或其化学等价物与受体结合的方法而使在活性状态下的受体稳定。
接触意味着把至少两部分放在一起,无论是在体外系统还是在体内系统中。
直接识别或被直接识别,与术语“候选化合物”相联系,意味着筛选针对组成型活化的受体、优选针对组成型活化的受体、最优选针对组成型活化的G蛋白偶联的细胞表面受体的候选化合物,并且评估该化合物的化合物效应。本术语在任何情形下都不应被解释或被理解为被包括或包括术语“非直接地识别”或“非直接地被识别”。
内源意味着由哺乳动物天然产生的物质。例如但却不限于,有关术语“受体”的内源是指由哺乳动物(例如但不限于,人)或病毒天然产生的受体。相反,术语“非内源”在本文中意味着不是由哺乳动物(例如但不限于人)或病毒天然产生的。例如但不限于这种受体,其在内源形式下并非组成型活化,但当对之进行操作而其组成型活化,这种受体被最优选地指称为“非内源性组成型活化的受体”,这两个用语都可被用来描述“体内”和“体外”系统。例如,在筛选过程中,内源的或非内源的受体可被用于体外筛选系统,这也只作为例证而不是限制。作为进一步的例子而不是限制,当操作哺乳动物的基因组以包括非内源组成型活化受体时,可以通过体内系统筛选候选化合物。
在本文的上下文中,“G蛋白偶联受体融合蛋白”和“GPCR融合蛋白”各指包含内源性组成型活化的GPCR或非内源性组成型活化的GPCR的非内源蛋白与至少一个G蛋白的融合,该G蛋白最优选是G蛋白的α亚基(它是与GTP结合的亚基),其中G蛋白的类型优选是天然情况下与内源性GPCR偶联的G蛋白的类型。例如(但不限于),在内源状态,如果G蛋白“Gsα”是与GPCR偶联的主要G蛋白,基于这一具体GPCR的GPCR融合蛋白就是包含与Gsα融合的GPCR的非内源蛋白;在某些情况下,正如下文将要描述的那样,非主要G蛋白也可以和GPCR融合。G蛋白与组成型活化的GPCR的C末端可直接融合,也可在其两者之间存在间隔子。
宿主细胞意味着能在其中插入质粒和/或载体的细胞。在原核宿主细胞情形下,当宿主细胞复制时质粒典型地以自主分子方式复制(在一般情况下,质粒在复制后被分离出来以被引入真核宿主细胞中);在真核宿主细胞情形下,质粒被整合进宿主细胞的细胞DNA中,因而,当真核细胞复制时,质粒复制。为在此公开的本发明的目的,宿主细胞优选是真核细胞,更优选是哺乳动物细胞,最优选地是从Hek-293、Hek-293T和COS-7细胞中选择出来的细胞。
非直接地识别或非直接地被识别意味着发现药物的传统方法,该方法涉及对内源受体特异的内源配体的识别、筛选针对受体的候选化合物、确定那些干扰或竞争配体-受体相互作用的化合物、检测化合物对至少一个与活化受体相关的第二信使途径影响的效率。
抑制,与用语“应答”相联系,意味着在化合物存在时应答被降低或阻止,这正好与该化合物不存在时相反。
反激动剂意味着这样的物质(例如,配体、候选化合物),它们与受体的内源形式或受体的组成型活化形式结合,并且将由受体的活性形式引发的基本细胞内反应抑制到正常基础水平以下,该活性水平是在没有激动剂或部分激动剂的情况下观察的,或者它们降低GTP与膜的结合。与在没有反激动剂情况下的基本反应相比,基本细胞内反应在反激动剂的存在下优选被抑制至少30%、更优选至少50%、最优选至少75%。。
已知受体意味着其特异的内源配体已被识别的内源受体。
配体意味着对内源的天然受体有特异性的内源的天然分子。
关于内源受体的核苷酸和/或氨基酸序列的突变意味着这些内源序列的特定改造,从而使内源的非组成型活化受体的突变型能造成受体的组成型活化。对于特定序列的等价物,人受体的后续突变型被认为是人受体的首次突变的等价物,如果(a)后续突变型受体的组成型活化水平与受体的首次突变所表明的在本质上一样;和(b)在后续突变型受体和受体的首次突变之间的序列同源性的百分数是至少80%,更优选地是至少90%,最优选地是至少95%。在理想的情况下,考虑到在此公开的用于进行组成型活化的最优选的盒包括在内源和非内源型GPCR之间发生变化的单一氨基酸和/或密码子,序列同源性的百分数应是至少98%。
非孤儿受体是指特异于天然存在的内源配体的天然存在的内源分子,其中配体与受体的结合使胞内信号途经得以活化。
孤儿受体意味着这样的内源受体,其特异的内源配体尚未被识别或尚未知。
药物组合物意味着包括至少一种活性成分的组合物,借助此活性成分可以研究该组合物在哺乳动物(例如但不限于人体)中特定的效果。本领域的那些普通技术人员将能够理解和正确评价那些适于确定活性成分是否具有基于技术人员需要的预期效果的技术。
质粒意味着载体和cDNA的结合体。一般,为cDNA复制和/或表达蛋白质的目的将质粒引进宿主细胞。
刺激,与术语“应答”相联系,意味着当一种化合物存在时比当它不存在时应答增强。
针对cDNA的载体意味着能够将至少一个cDNA掺入其中且能导入到宿主细胞中的环形DNA。
下面部分的顺序安排是为了表达效果,而不能被解释为对下面的公开或权利要求的限制。A.引言
本专利文件中公开的组成型活化形式的已知G蛋白偶联的受体可根据本领域技术人员所熟知的定点突变的方法制备。用于对侯选化合物直接识别的组成型活化的受体优选通过在细胞内环中特定位置,更优选在细胞内环3(IC3)的区域内,突变该受体而实现。这种突变可能产生一种组成型活化的非内源受体,这通过该受体功能活性的增加,例如第二信使活性水平的增加而得以证实。尽管可使用标准的定点诱变的方法,优选在普通转让的审查未决的US09/170496(在此引用作为参考)中说明的方法。
下表B列出了被转变为其非内源形式的已知的内源GPCR,其相应的G蛋白和内源配体。
表B
| 已知GPCR | G蛋白 | 内源配体 |
| 5HT-1A | Gi | 5-羟色胺 |
| 5HT-1B | Gi | 5-羟色胺 |
| 5HT-1D | Gi | 5-羟色胺 |
| 5HT-1E | Gi | 5-羟色胺 |
| 5HT-1F | Gi | 5-羟色胺 |
| 5HT-2B | Gi | 5-羟色胺 |
| 5HT-4A | N/I | 5-羟色胺 |
| 5HT-4B | N/I | 5-羟色胺 |
| 5HT-4C | N/I | 5-羟色胺 |
| 5HT-4D | N/I | 5-羟色胺 |
| 5HT-4E | N/I | 5-羟色胺 |
| 5HT-5A | 未知 | 5-羟色胺 |
| 5HT-6 | Gs | 5-羟色胺 |
| 5HT-7 | Gs | 5-羟色胺 |
| A VPR1 A | Gq | 精氨酸升压素 |
| A VPR1 B | Gq | 精氨酸升压素 |
| A VPR2 | Gs | 精氨酸升压素 |
| BBR3 | Gq | 铃蟾肽 |
| BDKR1 | Gq | 缓激肽 |
| BDKR2 | Gq | 缓激肽 |
| C3a | N/I | 过敏毒素 |
| C5a | N/I | 过敏毒素 |
| CB1 | Gi | 大麻苷 |
| CB2 | Gi | 大麻苷 |
| CCR2b | Gi | 单核细胞趋化蛋白(MCP) |
| CCR3 | Gi | Eotaxin,白细胞诱素-1,RANTES,MCP |
| CCR5 | Gi | MIP-1α,MIP-1β,RANTES |
| CCR8 | Gi | I-309,TARC,MIP-1β |
| CCR9 | N/I | 胸腺表达的趋化因子(TECK) |
| CRFR1 | Gs | 促肾上腺皮质激素释放因子 |
| CXCR4 | Gi | SDF1 |
| 多巴胺D1 | Gs | 多巴胺 |
| 多巴胺D2 | Gi | 多巴胺 |
| 多巴胺D3 | Gi | 多巴胺 |
| 多巴胺D5 | Gs | 多巴胺 |
| ETA | Gq | 内皮缩血管肽 |
| ETB | Gq | 内皮缩血管肽 |
| FPR1 | N/I | 甲酰肽 |
| FPRL1 | N/I | 甲酰肽 |
| GALR1 | Gi | 甘丙肽 |
| GALR2 | Gi/Gq | 甘丙肽 |
| GIP | N/I | 胃抑制性多肽 |
| mGluR1 | Gq | 谷氨酸 |
| GPR5 | N/I | 单C基元(SMC-1) |
| GPR24(已知为MCH或SLC-1) | Gi/Gq | 黑素浓缩激素 |
| GRPR | Gq | 胃泌素 |
| M1 | Gq | 乙酰胆碱 |
| M2 | Gi | 乙酰胆碱 |
| M3 | Gq | 乙酰胆碱 |
| M4 | Gi | 乙酰胆碱 |
| M5 | Gq | 乙酰胆碱 |
| MC3 | Gs | Melanocortin |
| NK1R | Gq | 物质P |
| NK2R | Gq | 神经激肽A |
| NK3R | Gq | 神经激肽B |
| NMBR | Gq | 神经调节肽B |
| NPY5 | Gi | 神经肽Y |
| NTSR1 | Gq | 神经降压素 |
| NTSR2 | Gq | 神经降压素 |
| OPRD | Gi | 鸦片样物质 |
| OPRL1 | Gi | 鸦片样物质 |
| OPRK | Gi | 鸦片样物质 |
| OPRM | Gi | 鸦片样物质 |
| OPRM1A | Gi | 鸦片样物质 |
| OX1R | N/I | Orexin |
| OX2R | N/I | Orexin |
| PACAP | Gs | 垂体腺苷酸环化酶活化肽 |
| PAF | N/I | 血小板活化因子 |
| PGE EP1 | N/I | 前列腺素 |
| PGE EP2 | Gs | 前列腺素 |
| PGE EP4 | N/I | 前列腺素 |
| PTHR1 | N/I | 甲状旁腺激素 |
| PTHR2 | N/I | 甲状旁腺激素 |
| SCTR | Gs | 促胰液素 |
| SST1 | Gi | 促生长抑制素 |
| SST2 | Gi | 促生长抑制素 |
| SST3 | Gi | 促生长抑制素 |
| SST4 | Gi | 促生长抑制素 |
| SST5 | Gi | 促生长抑制素 |
| TSHR | Gs | 甲状腺刺激激素 |
| VIPR | Gs | 血管活性肠肽 |
| VIPR2 | Gs | 血管活性肠肽 |
注:N/I指未指出。B.受体筛选
筛选对应于此处公开的已知GPCR的非内源组成型活化形式的候选化合物,可直接识别在这个细胞表面受体上起作用的候选化合物,而不需要使用受体的内源配体。通过确定此处公开的已知GPCR的内源形式在体内表达和/或过表达的区域,有可能确定与该受体表达或过表达关联的相关疾病/紊乱;这种方法在本专利申请文件中得以公开。
下表C列出了在体内表达和/或过表达的已知的GPCR和组织。列出的参考文献对这种组织表达提供支持。
表C
| 已知GPCRs | 表达部位 | 参考文献 |
| 5HT-1A | N/I | N/I |
| 5HT-1B | 纹状体 | Striatum Jin,H.等,267(9)J Biol Chem 5735(1992) |
| 5HT-1D | 大脑皮质 | Weinshank,R.L.等,89(8)Proc Natl Acad Sci USA3630(1992) |
| 5HT-1E | N/I | N/I |
| 5HT-1F | 脑 | Adham,N.等,90 Proc Natl Acad Sci USA 408(1993) |
| 5HT-2B | 各种组织,包括脑 | Kursar,J.D.,46(2 Mol Brain Pharmacol 227(1994) |
| 5HT-4A | 脑,肠和内腔 | Blondel,O.等,70 J Nerochem 2252(1998) |
| 5HT-4B | 脑,肠和内腔 | Blondel,O.等,70 J Nerochem 2252(1998) |
| 5HT-4C | 脑,肠和内腔 | Blondel,O.,70 J Nerochem 2252(1998) |
| 5HT-4D | 肠 | Blondel,O.等,70 J Neurochem 2252(1998) |
| 5HT-4E | 脑 | Claeysen,S.等,55(5)Mol Pharmacol 910(1999) |
| 5HT-5A | 脑 | Rees,S.等,355(3)FEBS Lett 242(1994) |
| 5HT-6 | 尾状核 | Kohen,R.等,66(1)J Neurochem 47(1996) |
| 5HT-7 | 脑,冠状动脉 | Bard,J.A.等,268(31)J Biol Chem 23422(1993) |
| AVPR1A | N/I | N/I |
| AVPR1B | 垂体 | Sugimoto,T.等,269(43)J.Biol.Chem 27088(1994) |
| AVPR2 | 肺,肾 | Fay,M.J.等,17(3)Peptides 477(1996) |
| BBR3 | 睾丸,肺肿瘤 | Fathi,Z.等,268(8)J.Biol.Chem.5979(1993) |
| BDKR1 | N/I | N/I |
| BDKR2 | N/I | N/I |
| C3a | 肺,脾,卵巢,胎盘,小肠和脑 | Ames,R.等,271(34)J.Biol.Chem 20231(1996) |
| C5a | N/I | N/I |
| CB1 | 脑 | Gerard,C.M.等,279 Biochem J.129(1991) |
| CB2 | 脾,巨嗜细胞 | Munro,S.等,365(6441)Nature 61(1993) |
| CCR2b | N/I | N/I |
| CCR3 | 子宫内膜 | Zhang,J.等,62(2)Biol Reprod 404(2000) |
| CCR5 | 胸腺,脾 | Raport,C.J.等,271(29)J Biol Chem 17161(1996) |
| CCR8 | 胸腺,脾和淋巴结 | Napolitano M.等,Fomm nodes(Geneva)1999 OctDec;9(4):315-24 |
| CCR9 | 胸腺 | Zaballos,A等,162(10)J.Immunol 5671(1999) |
| CRFR1 | 脑,垂体 | Perrin,M.H.等,133(6)Endocrinology 3058(1993) |
| CXCR4 | 结肠表皮细胞 | Jordan,N.J.等,104(8)J Clin Invest 1061(1999) |
| 多巴胺D1 | 尾状核,核子叶及嗅结节 | Dearry,A.等,347 Nature 72(1990) |
| 多巴胺D2 | 视网膜 | Dearry,A.等,11(5)Cell Mol.Neurobiol.437(1991) |
| 多巴胺D3 | 脑 | Schmauss,C.等,90(19)Proc Natl Acad Sci USA8942(1993) |
| 多巴胺D5 | 脑 | Sunahara,R.K.等,350(6319)Nature 614(1991) |
| ETA | 胎盘,子宫,睾丸,肾上腺 | Adachi,M.等,180(3)Biochem Biophys ResCommun 1265(1991) |
| ETB | N/I | N/I |
| FPR1 | N/I | N/I |
| FPRL1 | N/I | N/I |
| GALR1 | 下丘脑核,室旁核,视上核 | Gundlach,A.L.等,863 Ann NY Acad Sci 241(1998) |
| GALR2 | 海马,下丘脑,腺垂体 | Fatli,Z.等,51 Mol BrainRes 49(1997) |
| GIP | N/I | N/I |
| mGluR1 | 脑 | Stephan,D.等,35(12)Neuropharmacology 1649(1996) |
| GPR5 | 白细胞 | Shan,L.等,268(3)Biochem Biophys Res Commun938(2000) |
| GPR24(也被称为MCH或SLC-1) | 前脑,海马 | Kolakowki LF Jr.等,398(2-3)FEBS Lett 253(1996) |
| GRPR | 肺癌细胞 | Corjay,M.H等,266 J Biol Chem 18771(1991) |
| M1 | 心脏,胰脏和神经原细胞系 | Peralta,E.G.等,Embo J.cell lines 6(13)3923(1987) |
| M2 | 心脏,胰脏和神经原细胞系 | Peralta,E.G.等,Embo J.cell lines 6(13)3923(1987) |
| M3 | 心脏,胰脏和神经原细胞系 | Peralta,E.G.等,Embo J.cell lines 6(13)3923(1987) |
| M4 | 心脏,胰脏和神经原细胞系 | Peralta,E.G.等,Embo J.cell lines 6(13)3923(1987) |
| M5 | 脑 | Bonner,T.I.等,Neuron 1(5),403(1988) |
| MC3 | 脑,胎盘,肠 | Gantz I.等,268(11)J Biol Chem 8246(1993) |
| NK1R | 脊索,肺 | Taked,Y.等,179(3)Biochem Biophys Res Commun1232(1991) |
| NK2R | N/I | N/I |
| NK3R | N/I | N/I |
| NMBR | 肺癌细胞 | Corjay,M.H.等,266 J Biol Chem 18771(1991) |
| NPY5 | 下丘脑 | Gerald,C.等,382 Nature 168(1996) |
| NTSR1 | 脑,小肠 | Vita,N.等,17(1-2)FEBS Lett 139(1993) |
| NTSR2 | N/I | N/I |
| OPRD | 外周血淋巴细胞 | Wick,M.J.等,64(1)J.lymphocytes Neuroimmunol29(1996) |
| OPRL1 | N/I | N/I |
| OPRK | 胎盘,脑 | Manson,E.等,202(3)BiochemBiophys ResCommun 1431(1994) |
| OPRM | N/I | N/I |
| OPRM1A | N/I | N/I |
| OX1R | 下丘脑 | Sakurai T.等,92 Cell 573(1998) |
| OX2R | 下丘脑 | Sakurai T.等,92 Cell 573(1998) |
| PACAP | 脑 | Ogi,K.等,196(3)Biochem Biophys Res Commun1511(1993) |
| PAF | N/I | N/I |
| PGE EP1 | 肾脏 | Watabe,A.等,268(27)J Biol Chem 20175(1993) |
| PGE EP2 | 小肠 | Bastien,L.等,269(16)J.Biol.Chem 11873(1994) |
| PGE EP4 | N/I | N/I |
| PTHR1 | 骨,肾脏 | Schipani,E.等,132(5)Endocrinology 2157(1993) |
| PTHR2 | 脑,胰脏 | Usdin,T.B.等,270(26)J.Biol Chem 15455(1995) |
| SCIR | 胰脏,小肠 | Chow,B.K.,212(1)BiochemBiophys Res Commun204(1995) |
| SST1 | 空肠,胃 | Yamada Y.等,89 Proc Natl Acad Sci USA 251(1992) |
| SST2 | 小脑,肾脏 | Yamada Y.等,89 Proc Natl Acad Sci USA 251(1992) |
| SST3 | 脑,胰岛 | Yamada Y.等,6 Mol Endocrinol 2136(1992) |
| SST4 | 胎儿,成人脑,肺 | Rohser L.等,90(9)ProC Natl Acad Sci USA4146(1993) |
| SST5 | 垂体 | Panetta R.等,45(3)mol Pharmacol 417(1994) |
| TSHR | 后眼眶组织,突眼性甲状腺 | Feliciello A.et al 342 Lancet 337(1993) |
| VIPR | 肺 | Sreedharan,S.P.等,193(2)Biochem Biophys ResCommun 546(1993) |
| VIPR2 | 骨骼肌 | Adamou,J.E.等,209(2)Biochem Biophys ResCommun 385(1995) |
注:N/I指未指出。
制造可以证明是组成型表达的公开的已知GPCR的非内源形式,优选基于其与位于GPCR的TM6内部的脯氨酸残基的距离,这一算法规则公开在普通转让的审查未决的美国专利申请09/170496中,该申请引入此文作参考。该算法规则不是依据传统的序列比对来预测,而是依据与上述TM6脯氨酸残基的特定距离。通过使距该残基(估计位于受体的IC3区)16个氨基酸残基处的氨基酸残基发生突变,最好是突变为赖氨酸,可以获得这种活化。其他氨基酸也可用于这种突变,但优选赖氨酸残基。D.疾病/紊乱的识别和/或选择
正如下文将要详细描述的,用本发明的方法可识别针对非内源性组成型活化的GPCR的最优选的小分子化学化合物形式的反激动剂,部分激动剂和激动剂。这种化合物是治疗与这些受体有关的疾病的药物探索中先导调节物的理想候选者。在没有使用这种受体的内源配体的情况下,可直接识别这种化合物针对GPCR的能力,从而有可能开发药物组合物。
优选,当尚不清楚一种受体与何种疾病相关时,该已知GPCR的DNA序列被用来制作探针,用于进行(a)针对组织-mRNA的斑点印迹和/或(b)组织样品中所述受体表达的RT-PCR识别。在组织或疾病组织中受体的存在,或者与正常组织相比在疾病组织中受体的浓度提高,可被优选地用来识别治疗方法(包括但不限于)与那种疾病的关联。用这种方法也可很好地把受体定位于器官的区域。基于受体定位于其中的特定组织的已知功能,可推导出受体推定的功能性作用。E.候选化合物的筛选1.一般的GPCR筛选测定技术
当一种G蛋白受体变为组成型活化时,它与G蛋白(例如,Gq、Gs、Gi、Gz、Go)偶联并刺激GTP与G蛋白结合。接着,借助受体在正常情况下失活,G蛋白作为GTP酶慢慢地把GTP水解为GDP,然而,组成型活化的受体继续把GDP转化为GTP。GTP不可水解的类似物[35S]GTPγS,可用来监测与表达组成型活化受体与膜的结合。据报道,[35S]GTPγS可用来监测在配体存在或不存在的情形下G蛋白与膜的偶联。在本领域中著名和可行的其他例证中有此种监测的一个例证,它由Traynor和Nahorski在1995年所报道。本测定系统的一个优选的应用是为了初步筛选候选化合物,因为本系统对所有蛋白-偶联受体一般可行,而不考虑与受体的细胞内结构域相互作用的特定的G蛋白。2.特定的GPCR筛选测定技术
一旦应用“一般”G蛋白偶联的受体测定方法(即筛选是激动剂、部分激动剂或反激动剂的化合物的方法)识别出候选化合物,优选进一步筛选以确认该化合物与该受体位点相互作用。例如,应用“一般”测定方法识别的化合物可能不与受体结合,但可能仅仅从细胞内结构域与G蛋白“解偶联”。a.Gs,Gz和Gi
Gs刺激腺苷酸环化酶。另一方面,Gi(和Gz和Go)抑制该酶。腺苷酸环化酶催化ATP向cAMP的转化;因此,与Gs蛋白偶联的组成型活化的GPCRs与升高的细胞内cAMP水平相关联。在另一方面,与Gi(和Gz或Go)蛋白偶联的组成型活化的GPCRs与降低的细胞内cAMP水平相关联。一般情况参见“突触传导的非直接机制(IndirectMechanisms of Synaptic Transmission)”,第8章,
从神经到大脑(From Neuron To Brain)(第三版),Nichols,J.G.等编,Sinauer Associates,Inc.(1992)。因此,检测cAMP的方法可被用来确定一个侯选化合物是否是受体的如反激动剂(即能降低cAMP水平的化合物)等。可以利用本领域已知的测定cAMP的多种方法;最优选的方法依赖于在基于ELISA的方法中应用抗-cAMP的抗体。可被应用的另一类测定方法是一种第二信使报告基因系统测定法。基因上的启动子驱动由一个特别的基因所编码的蛋白质的表达。环AMP通过以下步骤促进基因的表达,即它响应促进cAMP的DNA结合蛋白或转录因子(CREB)的结合,接着转录因子在被称为cAMP效应元件的特别位点与启动子结合并驱动基因表达。报告基因系统可被构建为具有一个启动子,该启动子在报告基因(例如β-半乳糖苷酶或荧光素酶)的前面含有多个cAMP效应元件。因而,一个被组成型活化的连接Gs的受体引起cAMP的积累,cAMP接着激活该基因和报告蛋白质的表达。如β-半乳糖苷酶或荧光素酶等的报告蛋白质可用标准生化方法检测到(Chen等,1995)。b.Go和Gq
Go和Gq与磷脂酶C的活化相联系,磷脂酶C随后水解磷酸酯PIP2,并释放两种细胞内信使:二酰甘油(DAG)和肌醇-1,4,5-三磷酸酯(IP3)。IP3增加的积累与Gq-和Go-关联的受体相关联。一般情况参见“突触传导的非直接机制(Indirect Mechanisms of SynapticTransmission)”,第8章,从神经到大脑(
From Neuron To Brain)(第三版),Nichols,J.G.等编,Sinauer Associates,Inc.(1992)。测定IP3积累的方法可被用来确定一个候选化合物是否是例如针对Gq-或Go-关联受体等的反激动剂(即能降低IP3水平的化合物)。Gq关联受体也可用AP1报告基因测定方法来检测,因为Gq依赖的磷脂酶C引起含有AP1元件的基因活化;因而,活化的Gq关联受体将导致这种基因的表达增高,而其反激动剂将导致这种表达降低,激动剂将导致这种表达升高。进行这样的测定的商业方法是可以使用的。3.基于配体的确认实验
利用上述技术(或相当的技术)直接识别的侯选化合物接着最优选再利用一种基于配体的确认实验来证实,例如实施例8的方案中所公开的那种。这一步的重点在于该侯选化合物是通过直接识别;后续的确认(如有,使用内源配体)仅仅用来证实这种直接识别的侯选化合物靶向该受体。
例如,血清素拮抗剂(sumatriptan)是5-HT1B和5-HT1D受体的众所周知的激动剂,而naltrindole是OPM1D受体的众所周知的拮抗剂。相应的,可使用激动剂(sumatriptan)和/或拮抗剂(naltrindole)竞争性结合实验来证实,用不依赖配体的筛选技术(相应地分别包含非内源性组成型活化的5-HT1B或5-HT1D,和非内源性组成型活化的OPM1D)确定直接识别的那些侯选化合物,被用做确认的目的。本领域技术人员有能力选择用于基于配体的确认实验的技术。4.GPCR融合蛋白
非内源性组成型活化的GPCR用于筛选候选化合物,直接识别反激动剂、激动剂和部分激动剂,提出了一个有意思的筛选难题,确切地说,在没有内源配体结合的情况下,受体仍有活性。因此,为了区分存在或不存在候选化合物时的非内源受体,这种区分的目的是要了解这种化合物是否是所述受体的反激动剂、激动剂、部分激动剂或对该受体根本没有影响,优选的方法就是加强这种差异,一个优选的方法是使用GPCR融合蛋白。
一般来讲,应用上述公开的分析技术(还有其它的技术)一旦确定非内源GPCR为组成型活化,就可能确定与该内源GPCR偶联的优势G蛋白。G蛋白与GPCR的偶联提供了可评估的信号途径。因为最优选使用哺乳动物表达系统进行筛选,可期望在这个系统中有内源G蛋白存在。确切来说,非内源组成型活化的GPCR在这个系统中持续产生信号。从这点上,优选使信号得到加强,从而在例如受体的反激动剂存在时,很可能更方便地区分与反激动剂接触的不同受体,特别是在筛选的整个过程中。
GPCR融合蛋白的作用是增加G蛋白与非内源GPCR偶联的效应,GPCR融合蛋白优选用于筛选非内源组成型活化的GPCR,因为这种方法增强信号,因此最优选使用这样的筛选技术。重要的是有助于产生很大的“信噪”比,这种大信噪比对筛选此文公开的候选化合物是优选的。
用于GPCR融合蛋白表达的构建体的构建技术是本领域普通技术人员所熟悉。商业可得的表达载体和系统为实验者提供了各种可以满足特殊需要的方法。这种GPCR融合蛋白构建体重要的衡量标准,就是内源GPCR序列与G蛋白序列都符合读框(优选内源GPCR的序列位于G蛋白序列上游),并且必须去除或替代GPCR的“终止”密码子,以便根据GPCR的表达,也能表达G蛋白。GPCR可以直接连到G蛋白上,或在两者之间存在间隔残基(最好不超过12个,虽然本领域的普通技术人员可以很方便得知这一数字)。优选使用间隔子(基于方便),其中不使用的限制位点将在表达中有效地作为间隔子。最优选,在制造GPCR融合蛋白构建体之前首先确认与非内源GPCR偶联的G蛋白。因为只有很少的G蛋白已被识别,所以优选包含G蛋白序列(即通用G蛋白构建体)的构建体可在其中插入内源GPCR序列;这样可有效地大规模筛选大量具有不同序列的内源GPCRs。F.靶Gi偶联的GPCR和信号增强子Gs偶联的GPCR的共转染(基于cAMP的分析)
已知Gi偶联的受体抑制腺苷酸环化酶,并因此降低cAMP的产量,这导致难以评估cAMP的水平。检测作为受体(其活化时主要偶联Gi)组成型活化指示的cAMP产量降低的有效技术,可以通过将偶联GPCR的Gi与一个信号增强子(如在激活时主要偶联Gs的非内源性组成型活化受体,如以下公布的TSHR-A623I)共转染得以实现(此技术在本文中用偶联Gi受体GPR24举例说明)。显然,Gs偶联受体的组成型活化可基于cAMP产量的增加而确定。Gi偶联受体的组成型活化导致cAMP的产量降低。因此,这种共转染的方法意在有效地利用这些“相反”的效果。例如,非内源性组成型活化的Gs偶联受体(“信号增强子”)和内源性Gi偶联受体(“靶受体”)共转染提供了基本的cAMP信号(即,尽管Gi偶联的受体降低cAMP的水平,但这种“降低”的效果与组成型活化的Gs偶联的信号增强子所导致的cAMP水平的显著增加相关联)。从而,通过将信号增强子与组成型活化的靶受体共转染,由于Gi靶的活性增加(即,降低cAMP水平),预计cAMP将进一步降低(相对于基本水平)。
因此利用基于cAMP的分析对侯选化合物进行分析是可能的,但有两个限制性条件:首先,相对于Gi偶联的靶受体,可产生“相反”的效应,即,Gi偶联靶受体的反激动剂将增加可测定的cAMP信号,而Gi偶联靶受体的激动剂将降低该信号;第二,很显然,利用这种方法直接识别的侯选化合物应单独地评估,以确保其对信号增强受体无靶向作用(在针对共转染受体的筛选之前或以后进行)。G.药物化学
在一般但并非经常的情况下,对候选化合物直接识别优于通过组合化学技术产生的化合物联合使用,其中随机制备几千种化合物用于此分析。如此筛选的结果一般将是具有独特中心结构的化合物;其后,优选将这些化合物围绕着一种或多种优选的中心结构进行另外的化学修饰,以进一步加强其药用性质。这样的技术在该领域中是已知的,并不需要在本专利文件中详细描述。H.药物组合物
为进一步开发而选择出的候选化合物可应用本领域周知的技术制剂成药物组合物。适宜的可药用载体在本领域中是可得的;例如,参见Remington’s Pharmaceuctical Sciences,第16版,1980,MackPublishing Co.(Oslo等编)。I.其他应用
尽管本文公开的非内源的已知GPCRs的一个优选的用途是为了直接识别作为反激动剂、激动剂或部分激动剂(优选地作为药物使用)的候选化合物,已知GPCRs的这些形式也可被用于研究之用。例如,带有GPCRs的体外或体内系统可被用来阐释和理解这些受体在正常和患病的人体状况中的作用,也可理解当它应用于理解信号级联反应时组成型活化的作用。这些非内源性已知GPCR的价值由于其独特的特点使其作为研究工具的用途被强化,已知非内源GPCR受体可被用来理解这些受体在人体中的作用,即使在其内源配体被识别之前。所公开受体的其他应用对于本领域的技术人员将是明显的,特别是当他们阅读了本申请文件之后。实施例
下面提供的实施例,目的是要阐明而不是限制本发明。特异的核酸序列和氨基酸序列在此公开时,本领域的普通技术人员能够对这些序列进行较小的修饰,并且得到与下面报告的相同或基本相似的结果。使用或了解一个又一个序列框(如从大鼠的受体到人的受体或从人的受体A到人的受体B)的传统方式一般是基于序列对比技术,通过把序列排列对比来尽量确定共同的区域。此处公开的突变方法不依赖于这种方式,而是基于算法规则和与位于GPCR的TM6区中保守脯氨酸残基相隔的位置距离。一但这种方式确定,相信本领域的普通技术人员能够进行较小修饰以便得到与此处公开的基本相同的结果(如,组成型活化)。这些修饰被认为均在本公开的范围内。实施例1已知内源性GPCR的制备A通过标准PCR表达
以特定cDNA做模板并用有缓冲系统的rTth聚合酶(PerkinElmer)进行PCR,该缓冲液系统由生产商提供,各引物0.25μM,4种核苷酸各0.2mM。
用相应的限制性位点消化所产生的PCR片段,将其克隆于pCMV表达载体中。之后确定并证实核酸和氨基酸序列。参见下表D:
表D
B通过其他替代方法表达1、AVPR1A
| 受体识别 | 模板 | 循环条件分(’)/秒(”) | 5’引物(SEQ.ID.NO)和限制性位点 | 3’引物(SEQ.ID.NO)和限制性位点 |
| 5HT-1A | 基因组DNA | 94℃1’60℃1’72℃1’30” | CGGAAGCTTAGCCATGGATGTGCTCAGCCCTGGTCA(1);HindIII | CCGGAATTCCTGGCGGCAGAAGTTACACTTTAATG(2);EcoRI |
| 5HT-1B | 基因组DNA | 94℃1’60℃1’72℃1’30” | TCCAAGCTTGGGGCGAGGAGAGCCATGGAGGA(3);HindIII | GGCGAATTCACTTGTGCACTTAAAACGTATCAGTT(4);EcoRI |
| 5HT-1D | 基因组DNA | 94℃1’60℃1’72℃1’30” | ATCTACCATGTCCCCACTGAACCAGTCAGC(5) | ATAGAATTCGGAGGCCTTCCGGAAAGGGACAA(6);EcoRI |
| 5HT-1E | 基因组DNA | 94℃1’60℃1’72℃2’30” | CCACAGTGTCGACTGAAACAAGGGAAACATGAAC(7);SalII | CAGTATGCTCTCGGCATCTAATGAG(8) |
| 5HT-1F | 基因组DNA | 94℃1’60℃1’72℃2’10” | ATCACCATGGATTTCTTAAATTCATCTGATC(9) | TTAGGATCCACATCGACATCGCACAAGCTTTTG(10);BamHI |
| 5HT-2B | 子宫cDNA | 94℃1’60℃1’72℃1’30” | GAAAAGCTTGCCATGGCTCTCTCTTACAGAGTGTCTG(11);HindIII | GTTGGATCCTACATAACTAACTTGCTCTTCAGTTT(12);BamHI |
| 5HT-4A | 脑cDNA | 94℃1’60℃1’72℃1’30” | ATCACCATGGACAAACTTGATGCTAATGTGAG(13) | CCTGAATTCGAAGCATGATTCCAGGGATTCTGG(14);EcoRI |
| 5HT-4B | 脑cDNA | 94℃1’60℃1’72℃1’30” | ATCACCATGGACAAACTTGATGCTAATGTGAG(15) | AGGGAATTCAGTGTCACTGGGCTGAGCAGCCAC(16);EcoRI |
| 5HT-4C | 脑cDNA | 94℃1’60℃1’72℃1’30” | ATCACCATGGACAAACTTGATGCTAATGTGAG(17) | TTGGAATTCGGATGGTTTGGTCAATCTTCTCTTC(18);EcoRI |
| 5HT-4D | 5HT-4E DNA | 94℃1’60℃1’72℃2” | ATCACCATGGACAAACTTGATGCTAATGTGAG(19) | AGGGAATTCAAATCTTAGTACATGTGTGGATCCATTAAT(20);EcoRI |
| 5HT-4E | 脑cDNA | 94℃1’60℃1’72℃1’15” | ATCACCATGGACAAACTTGATGCTAATGTGAG(21) | TCAGAATTCGACAGGAACTGGTCTATTGCAGAA(22);EcoRI |
| 5HT-5A | 脑cDNA | 94℃1’60℃1’72℃2’10” | CCTAAGCTTGCCATGGATTTACCAGTGAACCTAACCTCC(23);HindIII | TCTGAATTCGTGTTGCCTAGAAAAGAAGTTCTTGA(24);EcoRI |
| 5HT-6 | 参见以下的替代方法 | 参见以下的替代方法 | 参见以下的替代方法 | 参见以下的替代方法 |
| 5HT-7 | 脑cDNA | 94℃1’72C2” | AGCGGAATTCGGCGGCGCGATGATGGACGTT(25);EcoRI | TTTCGGATCCATTGTTCTGCTTTCAATCAT(26);BamHI |
| A VPR1A | 参见以下的替代方法 | 参见以下的替代方法 | 参见以下的替代方法 | 参见以下的替代方法 |
| A VPR1A变体 | 参见以下的替代方法 | 参见以下的替代方法 | 参见以下的替代方法 | 参见以下的替代方法 |
| A VPR1B | 参见以下的替代方法 | 参见以下的替代方法 | 参见以下的替代方法 | 参见以下的替代方法 |
| A VPR2 | IMAGE 301449 | Pfu PCR94℃1’63℃1’72℃2” | CAGGAATTCAGAACACCTGCCCCAGCCCCAC(27);EcoRI | AGCGGATCCCGATGAAGTGTCCTTGGCCAGGGA(28);BamHI |
| BBR3 | 子宫cDNA | 94℃1’56℃1’72℃1’20” | ACAGAATTCAGAAGAAATGGCTCAAAGGCA(29);EcoRI | CATGGATCCTTGAAAAGCTAGAAACTGTCC(30);BamHI |
| BDKR1 | IMAGE1472696 | Pfu PCR94℃1’65℃1’72℃2” | TGTAAGCTTCAGGTCACTGTGCATGGCATCATC(31);HindIII | GCTGGATCCATTCCGCCAGAAAAGTTGGAAGATTTC(32);BamHI |
| BDKR2 | IMAGE1682455 | Pfu PCR94℃1’65℃1’72℃2” | ACTAAGCTTCCAAATGTTCTCTCCCTGGAAGATA(33);HindIII | GTTGAATTCCTGTCTGCTCCCTGCCCAGTCCTG(34);EcoRI |
| C3a | 基因组DNA | 94℃1’65℃1’72℃1’30” | CAGAAGCTTAGCAATGGCGTCTTTCTCTGCTG(35);HindIII | ACAGGATCCCACAGTTGTACTATTTCTTTCTGAAATG(36);BamHI |
| C5a | 胸腺 | 94℃1’65℃1’72℃1’10” | GGGAAGCTTAGGAGACCAGAACATGAACTCCTTC(37);HindIII | TGTGAATTCCACTGCCTGGGTCTTCTGGGCCAT(38);EcoRI |
| CB1 | EST01536 | Pfu PCR94℃1’65℃1’72℃2’30” | GGGAAGCTTTCTCAGTCATTTTGAGCTCAGCC(39);HindIII | TCAGAATTCCAGAGCCTCGGCAGACGTGTCTGT(40);EcoRI |
| CB2 | IMAGE1301708 | Pfu PCR94℃1’60℃1’72℃2” | CAAAAGCTTCTAGACAAGCTCAGTGGAAT℃TGA(41);HindIII | GCCGAATTCGCAATCAGAGAGGTCTAGATCTCTG(42);EcoRI |
| CCR2b | 基因组DNA | 94℃1’60℃1’72℃1’10” | GACAAGCTTCCCCAGTACATCCACAACATGC(43);HindIII | CTCGGATCCTAAACCAGCCGAGACTTCCTGCTC(44);BamHI |
| CCR3 | 基因组DNA | 94℃1’60℃1’72℃1’10” | ATCGCCATGACAACCTCACTAGATACAGTTGAG(45) | TCTGAATTCAAACACAATAGAGAGTTCCGGCTC(46);EcoRI |
| CCR5 | 基因组DNA | 94℃1’62℃1’72℃1’10” | GCAAAGCTTGGAACAAGATGGATTATCAAGTGTC(47);HindIII | TCCGGATCCCAAGCCCACAGATATTTCCTGCTC(48);BamHI |
| CCR8 | 基因组DNA | 94℃1’60℃1’72℃1’10” | TGAAAGCTTCCCGCTGCCTTGATGGATTATAC(49);HindIII | TGAGAATTCCAAAATGTAGTCTACGCTGGAGGAA(50);EcoRI |
| CCR9 | 基因组DNA | 94℃1’60℃1’72℃1’10” | ATCACCATGACACCCACAGACTTCACAAGCCCTATTCCTAACATGGCTGATGACTATGG(51) | GACGAATTCGAGGGAGAGTGCTCCTGAGGTTGT(52);EcoRI |
| CRFR1 | 垂体cDNA | 94℃1’65℃1’72℃1’20” | ATCACCATGGGAGGGCACCCGCAGCTCCGT(53) | CGGGAATTCGACTGCTGTGGACTGCTTGATGCT(54);EcoRI |
| CXCR4 | 基因组DNA | 94℃1’65℃72℃1’ | ATCACCATGGAGGGGATCAGTATATACACTTCAGATAACTACACCGAGGAAATG(55) | TCTGAATTCGCTGGAGTGAAAACTTGAAGACTCAG(56);EcoRI |
| 多巴胺D1 | 参见以下替代方法 | 参见以下替代方法 | 参见以下替代方法 | 参见以下替代方法 |
| 多巴胺D2 | 参见以下替代方法 | 参见以下替代方法 | 参见以下替代方法 | 参见以下替代方法 |
| 多巴胺D3 | 脑cDNA | 94℃1’62℃1’20”72℃1’20” | AAGAAGCTTGGCATCACGCACCTCCTCTGG(57);HindIII | GGCTCTAGAAATGGGTACAAAGAGTGTT(58)XbaI |
| 多巴胺D5 | 基因组DNA | 参见以下替代方法 | 参见以下替代方法 | 参见以下替代方法 |
| ETA | 参见以下替代方法 | 参见以下替代方法 | 参见以下替代方法 | 参见以下替代方法 |
| ETB | IMAGE1086987 | Pfu PCR94℃1’60℃1’72℃2’20” | CGGAAGCTTCTGGAGCAGGTAGCAGCATG(59);HindIII | CTTGGATCCAGATGAGCTGTATTTATTACTGGAACG(60);BamHI |
| FPR1 | IMAGE2153284 | 94℃1’63℃1’72℃2’30” | ATCACCATGGAGACAAATTCCTCTCTCCCC(61) | CCCGAATTCCTTTGCCTGTAACTCCACCTCTGC(62);EcoRI |
| FPRL1 | 基因组DNA | 94℃1’65℃1’72℃1’10” | GCAAAGCTTGCTGCTGGCAAGATGGAAACCAAC(63);HindIII | CCAGAATTCCATTGCCTGTAACTCAGTCTCTGC(64);EcoRI |
| GALR1 | 胃cDNA | 94℃1’60℃1’20”72℃1’20” | CCGGAATTCGCCGGGACAGCCCCGCGGGCC(65);EcoRI | GCAGGATCCTTATCACACATGAGTACAATTGGT(66);BamHI |
| GALR2 | 海马cDNA | 94℃1’62℃1’20”72℃1’20” | GGCGAATTCGGGGTCAGCGGCACCATGAACG(67);EcoRI | GTGGGATCCCAGCGCGCCCGCTAAGTGCT(68);BamHI |
| GIP | 脑cDNA | 94℃1’65℃1’72℃1’30” | CAGAAGCTTCGCCGCCCTCACGATGACTAC(69);HindIII | CGCGAATTCGCAGTAACTTTCCAACTCCCGGCT(70);EcoRI |
| mGluR1 | 参见以下替代方法 | 参见以下替代方法 | 参见以下替代方法 | 参见以下替代方法 |
| GPR5 | 基因组DNA | 94℃1’64℃1’72℃1’30” | TATGAATTCAGATGCTCTAAACGTCCCTGC(71);EcoRI | TCCGGATCCACCTGCACCTGCGCCTGCACC(72);BamHI |
| GPR24(也被称为MCH或SLC-1) | 参见以下替代方法 | 参见以下替代方法 | 参见以下替代方法 | 参见以下替代方法 |
| GRpR | 胃cDNA | 94℃1’56℃1’20”65℃1’20” | AGGAAGCTTTTAGGTGGGAAAAAAAATCTA(73);HindIII | CCGGAATTCAAGGGGCAAAATCAAGGGTCAA(74);EcoRI |
| M1 | 基因组DNA | 94℃1’60℃1’72℃1’50” | GCCAAGGTTAGCCACCATGAACACTTCAGCCC(75);HindIII | GGAGAATTCGCATTGGCGGGAGGGAGTGCGGTG(76);EcoRI |
| M2 | 基因组DNA | 94℃1’60℃1’72℃1’50” | ATCACCATGAATAACTCAACAAACTCCTCTAAC(77) | GATGAATTCCCTTGTAGCGCCTATGTTCTTATA(78);EcoRI |
| M3 | 基因组DNA | 94℃1’60℃1’72℃1’50” | ATCACCATGACCTTGCACAATAACAGTACAAC(79) | CTCGAAATTCCAAGGCCTGCTCGGGTGCGCGCT(80);EcoRI |
| M4 | 基因组DNA | 94℃1’60℃1’72℃1’50” | ATCACCATGGCCAACTTCACACCTGTCAA(81) | GCCGAATTCCCTGGCAGTGCCGATGTTCCGATA(82);EcoRI |
| M5 | 基因组DNA | 94℃1’60℃1’72℃1’50” | ATCACCATGGAAGGGCATTCTTACCACAAT(83) | GACGGATCCGGGTAGCTTGCTGTTCCCCTGCCA(84);BamHI |
| MC3 | 基因组DNA | 94℃1’54℃1’30”72℃1’20” | CAGGAATTCTGACAGCAATGAATGCTTCGT(85);EcoRI | AATGGATCCTATCCCAAGTTCATGCCGTTGCAG(86);BamHI |
| NK1R | 脑cDNA | 94℃1’65℃1’72℃1’50” | AGTAAGCTTTACGCCTAGCTTCGAAATGGAT(87);HindIII | TGTGAATTCGGAGAGCACATTGGAGGAGAAGCT(88);EcoRI |
| NK2R | 子宫cDNA | 94℃1’65℃1’72℃1’50” | TCCAAGCTTAGAAGCAGCCATGGGGACCTGTGACA(89);HindIII | AACGAATTCAATTTCAACATGAGTTTTGGTGGGGG(90);EcoRI |
| NK3R | 脑cDNA | 94℃1’65℃1’20”72℃1’20” | ATCTGCAGACCGGTGGCGATGGCACT(91) | ATGGGATCCAGAATATTCATCCACAGAGGTATAGG(92);BamHI |
| NMBR | 脑cDNA | 94℃1’65℃1’20”72℃1’20” | TGAGAATTCCAGCGGACTCTGCTGGAAAGGA(93);EcoRI | GTTGGATCCAGGTAGTGAGTTGAATGGCCA(94);BamHI |
| NPY5 | 基因组DNA | 94℃1’54℃1’30”72℃1’20” | GGAAAGCTTCAAGAAAGACTATAATATGGAT(95);HindIII | GGAGGATCCAGTGAGAATTATTACATATGAAG(96);BamHI |
| NTSR1 | 参见以下替代方法 | 参见以下替代方法 | 参见以下替代方法 | 参见以下替代方法 |
| NTSR2 | 参见以下替代方法 | 参见以下替代方法 | 参见以下替代方法 | 参见以下替代方法 |
| OPRD | 脑cDNA | 94℃1’65℃1’72℃1’15” | CGGAAGCTTGCAGCCATGGAACCGGCCCCCTCC(97);HindIII | GCCGAATTCGGCGGCAGCGCCACCGCCGGGACC(98);EcoRI |
| OPRL1 | 脑cDNA | 94℃1’65℃1’72℃1’15” | AGTAAGCTTGCAGGGCAGTGGCATGGAGCCC(99);HindIII | GCCGAATTCTGCGGGCCGCGGTACCGTCTCAGA(100);EcoRI |
| OPRK | 脑cDNA | 94℃1’65℃1’72℃1’15” | TTTAAGCTTGCAGCACTCACCATGGAATCCCCGAT(101);HindIII | CTACTGGTTTATTCATCCCATCGATGTC(102); |
| OPRM | 参见以下替代方法 | 参见以下替代方法 | 参见以下替代方法 | 参见以下替代方法 |
| OPRM1A | 参见以下替代方法 | 参见以下替代方法 | 参见以下替代方法 | 参见以下替代方法 |
| OX1R | 参见以下替代方法 | 参见以下替代方法 | 参见以下替代方法 | 参见以下替代方法 |
| OX2R | 脑cDNA | 94℃1’65℃1’72℃1’20” | ACCAAGCTTGAGCCCGTGATGTCCGGCACC(103);HindIII | CAGGGATCCTTGTCATATGAATAAATATT(104);BamHI |
| PACAP | 胎儿脑cDNA | 94℃1’65℃1’72℃1’30” | AGTAAGCTTGGCCAAGAAGTGTCATGGCTGGTG(105);HindIII | CATGAATTCGGTGGCCAGATTGTCAGCAGGGAG(106);EcoRI |
| PAF | 基因组DNA | 94℃1’63℃1’72℃2’30” | CTGAAGCTTCCAGCCCACAGCAATGGAGCCA(107);HindIII | CAGGAATTCATTTTTGAGGGGAATTGCCAGGGATCTG(108);EcoRI |
| PGEEP1 | cDNA克隆 | Pfu PCR94℃1’63℃1’72℃2’30” | ATCGCCATGAGCCCTTGCGGGCCCCTCAA(109) | TTGGAATTCGAAGTGGCTGAGGCCGCTGTGCCG(110);EcoRI |
| PGEEP2 | 胸腺cDNA | 94℃1’63℃1’72℃2’30” | GCAAAGCTTTTCCAGGCACCCCACCATGGGC(111);HindIII | CTGGAATTCAAGGTCAGCCTGTTTACTGGCATC(112);EcoRI |
| PGEEP4 | cDNA克隆 | Pfu PCR94℃1’60℃1’72℃2’30” | ATCATCATGTCCACTCCCGGGGTCAAT(113) | TGCGAATTCTATACATTTTTCTGATAAGTTCAGTGTT(114);EcoRI |
| PTHR1 | 参见以下替代方法 | 参见以下替代方法 | 参见以下替代方法 | 参见以下替代方法 |
| PTHR2 | 脑cDNA | 94℃1’65℃1’72℃1’50” | CTGAAGCTTCCTACAGCCGTTCCGGGCATG 115);HindIII | CGAGAACATCCTCAGTTTCTCCTTGG(116) |
| SCTR | 小肠 | 94℃1’65℃1’72℃1’45” | GGGAAGCTTGCGGGCACCATGCGTCCCCACCT(117);HindIII | AGCGAATTCGATGATGCTGGTCCTGCAGGTGCC(118);EcoRI |
| SST1 | 基因组DNA | 94℃1’65℃1’20”72℃1’20” | GCCGAATTCAGCTGGGATGTTCCCCAATGGC(119);EcoRI | CAGGGATCCTGCGTGGCCCGGGCTCAGAGCG(120);BamHI |
| SST2 | 参见以下替代方法 | 参见以下替代方法 | 参见以下替代方法 | 参见以下替代方法 |
| SST3 | 基因组DNA | 94℃1’65℃1’20”72℃1’20” | ACGGAATTCCCCTCAGCCATGGACATGCTTC(121);EcoRI | TGG3GATCCCCAGGCCCCTACAGGTAGCTG(122);BamHI |
| SST4 | 基因组DNA | 94℃1’65℃1’20”72℃1’20” | GCCGAATTCAGCTGCCCTGCGCCGGCACCCC(123);EcoRI | GAGGGATCCACGCAGGGTGGGTAGGGGAAGG(124);BamHI |
| SST5 | 基因组DNA | 94℃1’65℃1’20”72℃1’20” | TCTAAGCTTGCAGAGCCTGACGCACCCCAG(125);HindIII | CCTGAATTCCTGGGGGTGACACGGGGCCGCC(126);EcoRI |
| TSHR | 基因组DNA | 94℃1’65℃1’72℃2’30” | GGCGAATTCGGAGGATGGAGAAATAGCCCC(127);EcoRI | GTAGGATCCCCTACCATTGTGAGTAGTGTA(128);BamHI |
| VIPR | 肺cDNA | 94℃1’65℃1’72℃1’30” | CCGAAGCTTCAGGGCAGACCATGCGCCCGCCA(129);HindIII | TGGGAATTCGACCAGGGAGACTTCGGCTTGGAA(130);EcoRI |
| VIPR2 | 脑cDNA | 94℃1’65℃1’72℃1’30” | GCTAAGCTTGCCATGCGGACGCTGCTGCCTCCCGCG(131);HindIII | GTGGAATTCGATGACCGAGGTCTCCGTTTGCAG(132);EcoRI |
使用一模板和有缓冲系统的rTth聚合酶(Perkin Elmer)进行PCR,获得内源的人AVPR1A,缓冲液系统由生产商提供,各引物0.25μM,4种核苷酸各0.2mM。循环条件为30次循环的94℃1分钟,64℃1分钟,72℃1分钟30秒。用基因组DNA为模板,和用以下引物对:5’-ATCACCATGCGTCTCTCCGCCGGTCCCGA-3’(SEQ.ID.NO.:133)和5’-TTGTTCACCTCGATCATGGAGAAGA-3’(SEQ.ID.NO.:134)可获得5’PCR片段。使用IMAGE 1055179作为模板,用pfu聚合酶(Stratagene)及以下引物对:5’-CGCAGTACTTCGTCTTCTCCATGA-3’(SEQ.ID.NO.:135)和5’-CAAGAATTCAGTTGAAACAGGAATGAATTTGATGG-3’(SEQ.ID.NO.:136),可获得3’PCR片段。3’PCR片段的循环条件是:30次循环的94℃1分钟,60℃和72℃为1.5分钟。然后使用该5’和3’PCR片段作为共模板,SEQ.ID.NO.:133和SEQ.ID.NO.:136做引物,使用pfu聚合酶以获得全长cDNA。各PCR反应的循环条件是30次循环的94℃1分钟,65℃和72℃为2分10秒。
用EcoRI限制性位点消化所产生的PCR片段,将其克隆于EcoRIpCMV表达载体中。之后测定并证实核苷酸和氨基酸序列。2、AVPR1A变体
使用一模板和有缓冲系统的rTth聚合酶(Perkin Elmer)进行PCR,获得内源的人AVPR1A变体,缓冲液系统由生产商提供,各引物0.25μM,4种核苷酸各0.2mM。循环条件为30次循环的94℃1分钟,64℃1分钟,72℃1.5分钟。用基因组DNA为模板,SEQ.ID.NO.:133和SEQ.ID.NO.:134做引物,可获得5’PCR片段。使用IMAGE 1542469作为模板,SEQ.ID.NO.:136和5’-ACAGAATTCTCCAGTTCTCATTTTCTTATCCGTAC-3’(SEQ.ID.NO.:137)作为引物,用pfu聚合酶(Stratagene)可获得3’PCR片段。3’PCR片段的循环条件是:30次循环的94℃1分钟,65℃1分钟,72℃1.5分钟。然后使用该5’和3’PCR片段作为共模板,SEQ.ID.NO.:133和SEQ.ID.NO.:136做引物,使用pfu聚合酶以获得全长cDNA。各PCR反应的循环条件是30次循环的94℃1分钟,65℃1分钟,72℃2分10秒。
用EcoRI限制性位点消化所产生的PCR片段,将其克隆于EcoRIpCMV表达载体中。之后测定并证实核苷酸和氨基酸序列。3、AVPR1B
使用一模板和有缓冲系统的rTth聚合酶(Perkin Elmer)进行PCR,获得内源的人AVPR1B,缓冲液系统由生产商提供,各引物0.25μM,4种核苷酸各0.2mM。两个循环的PCR均采用以下循环条件:30次循环的94℃1分钟,65℃1分钟,72℃2秒。第一循环的PCR用垂体DNA为模板,包含HindIII位点的5’PCR引物,其序列为5’-GCAAAGCTTGCTCATGGATTCTGGGCCTCT-3’(SEQ.ID.NO.:138)。3’PCR引物包含EcoRI位点,序列为5’-TCTGAATTCAAAGATGATGGTCTCAGCGGTGCC-3’(SEQ.ID.NO.:139)。第二循环的PCR用垂体DNA为模板,5’PCR引物包含HindIII位点,序列为:5’-GCAAAGCTTGCTCATGGATTCTGGGCCTCTGTCCC-3’(SEQ.ID.NO.:140),以及3’PCR引物包含EcoRI位点,序列为5’-TCTGAATTCAAAGATGATGGTCTCAGCGGTGCCTTCCC-3’(SEQ.ID.NO.:141)。
用HindIII和EcoRI限制性位点消化所产生的PCR片段,并将其克隆于HindIII-EcoRI pCMV表达载体中。之后测定并证实核苷酸和氨基酸序列。4、5HT6
使用一模板和有缓冲系统的rTth聚合酶(Perkin Elmer)进行PCR,获得内源的人5HT6受体,缓冲液系统由生产商提供,各引物0.25μM,4种核苷酸各0.2mM。两个循环的PCR均采用以下循环条件:30次循环的94℃1分钟,60℃1分钟,72℃1分45秒。第一循环的PCR用尾状核DNA为模板,5’PCR引物包含HindIII位点,序列为5’-CATAAGCTTTCCCGCCACCCTATCACT-3’(SEQ.ID.NO.:142),以及3’PCR引物包含EcoRI位点,序列为5’-ACTGAATTCTGCTCAATCCAGCTCCCCA-3’(SEQ.ID.NO.:143)。第二循环的PCR也用尾状核DNA为模板,5’PCR引物包含EcoRV位点,序列为:5’-CCTCGGATATCATGGTCCCAGAGCCGGGCCC-3’(SEQ.ID.NO.:144),以及3’PCR引物包含XbaI位点,序列为5’-CAGCTCTAGATTGGCCAGCCCCAAGCCCGGGT-3’(SEQ.ID.NO.:145)。
之后测定并证实核苷酸和氨基酸序列。5、多巴胺D1
多巴胺D1是从来自美国典型培养物保藏中心(ATCC)的全长cDNA克隆中亚克隆得到的。6、多巴胺D2
多巴胺D2是从来自美国典型培养物保藏中心(ATCC)的全长cDNA克隆中亚克隆得到的。7、多巴胺D5
为了获得多巴胺D5,使用基因组cDAN为模板和有缓冲系统的rTth聚合酶(Perkin Elmer)进行PCR,缓冲液系统由生产商提供,各引物0.25μM,4种核苷酸各0.2mM。
得到的多巴胺D5在其编码区内不含有内含子。但是,多巴胺D5受体包含两个假基因,其编码区中有8bp的移码插入片段。为了避免这两个假基因,将该移码插入片段的5’和3’的DNA片段各从基因组DNA扩增。该5’PCR片段利用以下引物对得到:
5’-CCTGAATTCCAGCCCGAAATGCTGCCGCCAG-3’(SEQ.ID.NO.:146;有义)和
5’-GGTCCACGCTGATGACGCACAGGTTC-3’(SEQ.ID.NO.:147;反义),并且3’PCR引物利用以下引物对获得:5’-GAACCTGTGCGTCATCAGCGTGGACC-3’(SEQ.ID.NO.:148;有义)和5’-TGCGGATCCATGAGGGGGTTTCTTAATG-3’(SEQ.ID.NO.:149;反义)进行扩增。然后将5’和3’PCR片段用做共模板,以获得全长的cDNA,使用pfu聚合酶和SEQ.ID.NO.:146和SEQ.ID.NO.:149作为引物。各PCR反应的循环条件是30次循环的94℃1分钟,64℃2分钟30秒,72℃1分30秒。
用HindIII和EcoRI限制性位点消化所产生的PCR片段,将其克隆于HindIII-EcoRI pCMV表达载体中。之后测定并证实核苷酸和氨基酸序列。8、ETA
为了获得内源性人ETA,使用一模板和有缓冲系统的rTth聚合酶(Perkin Elmer)进行PCR,缓冲液系统由生产商提供,各引物0.25μM,4种核苷酸各0.2mM。循环条件是:30次循环的94℃1分钟,65℃1分钟,72℃2秒。包含HindIII位点的5’PCR片段是利用基因组DNA为模板,和以下引物对获得的:
5’-CGGAAGCTTCTGGAGCAGGTAGCAGCATG-3’(SEQ.ID.NO.:150)和5’-TGGGCAATAGTTGTTGCATTGAGCCA-3’(SEQ.ID.NO.:151)。包含BamHI位点的3’PCR片段通过pfu聚合酶(Strategene),用IMAGE 666747为模板,和用以下引物对获得:5’-CTAATTTGGTCCTACCCAGCAATGGC-3’(SEQ.ID.NO.:152)和5’-CTTGGATCCAGATGAGCTGTATTTATTACTGGAACG-3’(SEQ.ID.NO.:153)。
3’PCR反应的循环条件是:30次循环的94℃1分钟,64℃1分钟,72℃2秒。然后使用该5’和3’PCR片段作为共模板,使用pfu聚合酶(Stratagene),和以下引物:
5’-AATAAGCTTCAAGATGGAAACCCTTTGCCTCAG-3’(SEQ.ID.NO.:154)和5’-CGTTCATGCTGTCCTTATGGCTGCTC-3’(SEQ.ID.NO.:155)从而获得全长的cDNA。为得到该全长克隆体,PCR循环条件是30次循环的94℃1分钟,65℃1分钟,72℃2分10秒。
用EcoRI限制性位点消化所产生的PCR片段,将其克隆于EcoRIpCMV表达载体中。之后测定并证实核苷酸和氨基酸序列。9、mGluR1
为了得到内源性人mGluR1,使用一模板和有缓冲系统的rTth聚合酶(Perkin Elmer)进行PCR,缓冲液系统由生产商提供,各引物0.25μM,4种核苷酸各0.2mM。PCR第一循环条件是:30次循环的94℃1分钟,65℃1分钟,72℃1分50秒。包含SalI位点的5’PCR片段是利用海马DNA为模板,和用以下引物对:
5’-GCAGGCTGTCGACCTCGTCCTCACCACCATGGTC-3’(SEQ.ID.NO.:156)和
5’-AATGGGCTCACAGCCTGTTAGATCTGCATTGGGCCAC-3’(SEQ.ID.NO.:157)获得的。
中间PCR片段利用基因组DNA为模板获得的,其循环条件是:30次循环的94℃1分钟,65℃1分钟,72℃1分50秒,和使用以下引物对:5’-TAACAGGCTGTGAGCCCATTCCTGTGCG-3’(SEQ.ID.NO.:158)和
5’-TTAGAATTCGCATTCCCTGCCCCTGCCTTCTTTC-3’(SEQ.ID.NO.:159)。
包含BamHI位点的3’PCR片段是利用基因组DNA为模板,和以下引物对:
5’-TGCGAATTCTAATGGCAAGTCTGTGTCATGGTC-3’(SEQ.ID.NO.:160)和
5’-TCCGGATCCCAGGGTGGAAGAGCTTTGCTTGTA-3’(SEQ.ID.NO.:161)获得的。3’PCR反应的循环条件是:30次循环的94℃1分钟,65℃1分钟,72℃1分15秒。
用SalI和BamHI限制性位点消化所产生的PCR片段,将其克隆于SalI-BamHI pCMV表达载体中。之后测定并证实核苷酸和氨基酸序列。10、GPR24(也被称为MCH或SLC-1)
内源性人GPR24通过使用基因组DNA为模板及有缓冲系统的rTth聚合酶(Perkin Elmer)进行PCR而获得,缓冲液系统由生产商提供,各引物0.25μM,4种核苷酸各0.2mM。循环条件是:30次循环的94℃1分钟,56℃1分钟,72℃1分20秒。包含HindIII位点的5’PCR引物,序列为:
5’-GTGAAGCTTGCCTCTGGTGCCTGCAGGAGG-3’(SEQ.ID.NO.:162),以及包含EcoRI位点的3’PCR引物,序列为:5’-GCAGAATTCCCGGTGGCGTGTTGTGGTGCCC-3’(SEQ.ID.NO.:163)。
该1.3kb的PCR片段用HindIII和EcoRI消化,然后克隆于CMVp表达载体的HindIII-EcoRI位点。后来由Lakaye等所做的克隆实验显示,在该基因的编码区内有一个内含子。因此,该cDNA的5’末端通过使用Clontech的marathon-ready海马cDNA为模板,按照供应商建议的循环条件,进行5’RACE PCR而获得。第一循环和第二循环PCR的5’RACE PCR如下:
5’-CATGAGCTGGTGGATCATGAAGGG-3’(SEQ.ID.NO.:164)和5’-ATGAAGGGCATGCCCAGGAGAAAG-3’(SEQ.ID.NO.:165)。
之后测定并证实核苷酸和氨基酸序列。11、NTSR1
内源性人NTSR1使用一模板和有缓冲系统的rTth聚合酶(PerkinElmer)进行PCR而获得,缓冲液系统由生产商提供,各引物0.25μM,4种核苷酸各0.2mM。循环条件是:30次循环的94℃1分钟,60℃1分钟,72℃1分10秒。包含HindIII位点的5’PCR片段是利用基因组DNA为模板,和用以下引物对:
5’-CCCAAGCTTCCAGCCCCGGAGGCGCCGGAC-3’(SEQ.ID.NO.:166)和
5’-TGAAGGTGTTGACCTGTATGACGACCTTGACGGTGGG-3’(SEQ.ID.NO.:167)获得的。包含EcoRI位点的3’PCR片段是利用脑cDNA为模板,和用以下引物对:
5’-GGTCGTCATACAGGTCAACACCTTCATGTCCTTCATA-3’(SEQ.ID.NO.:168)和
5’-CACGAATTCGTACAGCGTCTCGCGGGTGGCATT-3’(SEQ.ID.NO.:169)获得的。3’PCR反应的循环条件是:30次循环的94℃1分钟,60℃1分钟,72℃1分10秒。然后使用该5’和3’PCR片段作为共模板,使用pfu聚合酶(Stratagene),和引物:5’-ATCACCATGCGCCTCAACAGCTCCGC-3’(SEQ.ID.NO.:170)和SEQ.ID.NO.:169,从而获得全长的cDNA。各PCR循环条件是30次循环的94℃1分钟,65℃1分钟,72℃2分10秒。
用HindIII和EcoRI限制性位点消化所产生的PCR片段,将其克隆于HindIII-EcoRI pCMV表达载体中。之后测定并证实核苷酸和氨基酸序列。12、NTSR2
内源性人NTSR2使用一模板和有缓冲系统的rTth聚合酶(PerkinElmer)进行PCR而获得,缓冲液系统由生产商提供,各引物0.25μM,4种核苷酸各0.2mM。循环条件是:30次循环的94℃1分钟,65℃1分钟,72℃1分15秒。5’PCR片段是利用IMAGE 1537523为模板,和用以下引物对:
5’-ATCACCATGGAAACCAGCAGCCCGCGGC-3’(SEQ.ID.NO.:171)和5’-CGGGGTAGAAGTGGACGGCACTTGGG-3’(SEQ.ID.NO.:172)获得的。包含EcoRI位点的3’PCR片段是利用尾状核cDNA为模板,和以下引物对:5’-GCTCCCAAGTGCCGTCCACTTCTACC-3’(SEQ.ID.NO.:173)和
5’-TTAGAATTCGGTCCGGGTTTCTGGGGGATCC-3’(SEQ.ID.NO.:174)获得的。3’PCR反应的循环条件是:30次循环的94℃1分钟,60℃1分钟,72℃1分20秒。然后使用该5’和3’PCR片段作为共模板,使用pfu聚合酶(Stratagene),和引物SEQ.ID.NO.:171和SEQ.ID.NO.:174,从而获得全长的cDNA。该全长克隆的PCR循环条件是30次循环的94℃1分钟,60℃1分钟,72℃2分10秒。
用EcoRI限制性位点消化所产生的PCR片段,将其克隆于EcoRIpCMV表达载体中。之后测定并证实核苷酸和氨基酸序列。13、OPRM1
内源性人OPRM1使用一模板和有缓冲系统的rTth聚合酶(PerkinElmer)进行PCR而获得,缓冲液系统由生产商提供,各引物0.25μM,4种核苷酸各0.2mM。包含HindIII位点的5’PCR片段是利用基因组DNA为模板,以下引物对:
5’-CCCAAGCTTCAGTACCATGGACAGCAGCGCTGCC-3’(SEQ.ID.NO.:175)和
5’-CATCTTGGTGTATCTGACAATCACATACATGACCAGGAA-3’(SEQ.ID.NO.:176)获得的。
中间PCR片段利用基因组DNA为模板获得,循环条件是:30次循环的94℃1分钟,60℃1分钟,72℃40秒,和用以下引物对:5’-GTATGTGATTGTCAGATACACCAAGATGAAGACTGCCAC-3’(SEQ.ID.NO.:177)和
5’-TACAATCTATGGAACCTTGCCTGTATTTTGTTGTAGCCA-3’(SEQ.ID.NO.:178)。3’PCR片段是利用脑cDNA为模板,以下引物对:
5’-CAAAATACAGGCAAGGTTCCATAGATTGTACACTAACAT-3’(SEQ.ID.NO.:179)和
5’-CGGGCAACGGAGCAGTTTCTGCTTCAG-3’(SEQ.ID.NO.:180)获得的。3’PCR反应的循环条件是:30次循环的94℃1分钟,63℃1分钟,72℃1分15秒。
5’PCR片段和中间PCR片段被用做模板,使用pfu聚合酶(Stratagene),以及引物对SEQ.ID.NO.:175和SEQ.ID.NO.:178,获得OPRM1的5’区到中部区(“5’-中部PCR片段”),循环条件如下:30次循环的94℃1分钟,63℃1分钟,72℃1分15秒。
然后将5’-中部PCR片段和3’PCR片段作为模板,使用pfu聚合酶(Stratagene),以及引物SEQ.ID.NO.:175和SEQ.ID.NO.:180,获得全长cDNA。该全长PCR反应的循环条件如下:30次循环的94℃1分钟,65℃1分钟,72℃1分15秒。
用HindIII限制性位点消化所产生的PCR片段,将其克隆于HindIIIpCMV表达载体中。之后测定并证实核苷酸和氨基酸序列。14、OPRM1A
内源性人OPRM1A使用一模板和有缓冲系统的rTth聚合酶(Perkin Elmer)进行PCR而获得,缓冲液系统由生产商提供,各引物0.25μM,4种核苷酸各0.2mM。循环条件是30次循环的94℃1分钟,65℃1分钟,72℃40秒。包含HindIII位点的5’PCR片段是利用基因组DNA为模板,以引物SEQ.ID.NO.:175和SEQ.ID.NO.:176获得的。
中间PCR片段利用基因组DNA为模板,以引物SEQ.ID.NO.:177和SEQ.ID.NO.:178获得的,其循环条件是:30次循环的94℃1分钟,60℃1分钟,72℃40秒。
3’PCR片段是利用基因组DNA为模板,以引物SEQ.ID.NO.:179和SEQ.ID.NO.:180获得的。3’PCR反应的循环条件是:30次循环的94℃1分钟,60℃1分钟,72℃1分30秒。
5’PCR片段和中间PCR片段被用做共模板,使用pfu聚合酶(Stratagene),以及引物SEQ.ID.NO.:175和SEQ.ID.NO.:178,获得OPRM1A的5’区到中部区(“5’-中部PCR片段”),循环条件如下:30次循环的94℃1分钟,63℃1分钟,72℃1分15秒。
然后将5’-中部PCR片段和3’PCR片段作为共模板,使用pfu聚合酶(Stratagene),以及引物SEQ.ID.NO.:175和SEQ.ID.NO.:180,获得全长cDNA。循环条件如下:30次循环的94℃1分钟,65℃1分钟,72℃1分15秒。
用HindIII限制性位点消化所产生的PCR片段,将其克隆于HindIIIpCMV表达载体中。之后测定并证实核苷酸和氨基酸序列。15、OX1R
OX1R EST克隆40608是一种全长的cDNA克隆。但其包含一个4bp移码插入片段。为了去除该插入片段,该移码插入的5’和3’片段各用EST克隆40608为模板和两个引物对进行PCR获得。包含EcoRI位点的5’引物对如下
5’-ATGGAATTCTGCTGCAGCGGCTCCTGAGCTC-3’(SEQ.ID.NO.:181;有义)和
5’-ACGGACACAGCCTGTAGATAGGGGATGACCTTGCAG-3’(SEQ.ID.NO.:182;反义),包含一个BamHI位点的3’引物对如下5’-ATCCCCTATCTACAGGCTGTGTCCGTGTCAGTGGCAG-3’(SEQ.ID.NO.:183;有义)和
5’-GGAGGATCCAGGGCAGCCCTCGCTCAGGGC-3’(SEQ.ID.NO.:184;反义)。然后使用5’和3’PCR片段作为共模板,以SEQ.ID.NO.:181和SEQ.ID.NO.:184为引物得到全长cDNA。各PCR反应的循环条件是:30次循环的94℃1分钟,65℃2分30秒,72℃1分30秒。
用EcoRI和BamHI限制性位点消化所产生的PCR片段,将其克隆于EcoRI-BamHI pCMV表达载体中。之后测定并证实核苷酸和氨基酸序列。16、PTHR1
内源性人PTHR1使用一模板和有缓冲系统的rTth聚合酶(PerkinElmer)进行PCR而获得,缓冲液系统由生产商提供。循环条件是:30次循环的94℃1分钟,65℃1分钟,72℃1分30秒。包含HindIII位点的5’PCR片段是利用肾cDNA为模板,和以下引物对:5’-CGCAAGCTTAGGCGGTGGCGATGGGGACCGCC-3’(SEQ.ID.NO.:185)和5’-GGATGTGGTCCCATTCCGGCAGACAG-3’(SEQ.ID.NO.:186)获得的。包含EcoRI位点的3’PCR片段是使用pfuPCR(Stratagene)和IMAGE 1624048为模板,以及以下引物对:5’-AGGAGGCACCCACTGGCAGCAGGTA-3’(SEQ.ID.NO.:187)和
5’-GCCGAATTCCATGACTGTCTCCCACTCTTCCTG-3’(SEQ.ID.NO.:188)获得的。3’PCR反应的循环条件是:30次循环的94℃1分钟,65℃1分钟,72℃1分30秒。然后使用5’和3’PCR片段作为共模板,以SEQ.ID.NO.:185和SEQ.ID.NO.:188为引物,pfu聚合酶(Stratagene)扩增全长cDNA。全长克隆的PCR循环条件是:30次循环的94℃1分钟,65℃1分钟,72℃3秒。
用HindIII和EcoRI限制性位点消化所产生的PCR片段,将其克隆于HindIII-EcoRI pCMV表达载体中。之后测定并证实核苷酸和氨基酸序列。17、SST2
SST2是通过将EST 06818亚克隆于pCMV载体中获得的。
下表E显示了以上公开的内源受体可能位于的GenBank接入号,以及提供其所述内源核酸和氨基酸序列。
表E
实施例2制备非内源性的已知GPCR的变体A、定点诱变
| 受体识别 | GenBank接入号 |
| 5HT-1A | X13556 |
| 5HT-1B | D10995 |
| 5HT-1D | M81589 |
| 5HT-1E | M91467 |
| 5HT-1F | L04962 |
| 5HT-2B | X77307 |
| 5HT-4A | Y08756 |
| 5HT-4B | Y12505 |
| 5HT-4C | Y12506 |
| 5HT-4D | Y12507 |
| 5HT-4E | AJ011371 |
| 5HT-5A | X81411 |
| 5HT-6 | L41147 |
| 5HT-7 | L21195 |
| A VPR1A | AF030625 |
| A VPR1B | D31833 |
| A VPR2 | NM_000054 |
| BBR3 | X76498 |
| BDKR1 | AJ238044 |
| BDKR2 | NM_000623 |
| C3a | U62027 |
| C5a | M62505 |
| CB1 | X54937 |
| CB2 | X74328 |
| CCR2b | U03882 |
| CCR3 | U28694 |
| CCR5 | U54994 |
| CCR8 | U45983 |
| CCR9 | AJ132337 |
| CRFR1 | L23332 |
| CXCR4 | AJ224869 |
| 多巴胺D1 | X55758 |
| 多巴胺D2 | S62137 |
| 多巴胺D3 | U32499 |
| 多巴胺D5 | M67439 |
| ETA | X61950 |
| ETB | L06623 |
| FPR1 | M60627 |
| FPRL1 | M76672 |
| GALR1 | L34339 |
| GALR2 | AF040630 |
| GALR3 | AF073799 |
| GIP | U39231 |
| mGluR1 | L76627 |
| GPR5 | L36149 |
| GPR24(也被称为MCH或SLC-1) | U71092 |
| GRPR | M73481 |
| M1 | X15263 |
| M2 | X15264 |
| M3 | X15266 |
| M4 | X15265 |
| M5 | M80333 |
| MC3 | L06155 |
| NK1R | M74290 |
| NK2R | M57414 |
| NK3R | M89473 |
| NMBR | M73482 |
| NPY5 | U94320 |
| NTSR1 | X70070 |
| NTSR2 | Y10148 |
| OPRD | U07882 |
| OPRL1 | X77130 |
| OPRK | U11053 |
| OPRM | L25119 |
| OPRM1A | L25119 |
| OX1R | AF041243 |
| OX2R | AF041245 |
| PACAP | D17516 |
| PAF | S56396 |
| PGE EP1 | L22647 |
| PGE EP2 | U19487 |
| PGE EP4 | NM_000958 |
| PTHR1 | L04308 |
| PTHR2 | U25128 |
| SCTR | U28281 |
| SST1 | M81829 |
| SST2 | M81830 |
| SST3 | M96738 |
| SST4 | D16826 |
| SST5 | D16827 |
| TSHR | AF035261 |
| VIPR | L13288 |
| VIPR2 | X95097 |
相信本领域的普通技术人员有能力选择用于核酸序列突变的技术。下面提供的就是用于制造以上所公开的几种人GPCR非内源形式的方法。下面公开的突变是基于算法规则方法,由此第16位氨基酸(位于GPCR的IC3区域)由保守的脯氨酸残基(位于GPCR的TM6区域,接近TM6/IC3交界处)发生突变,最优选突变为赖氨酸残基。
本实施例2的多数实施例中,使用以上公开的算法以识别被突变的氨基酸残基。然而以下公开的几种GPCR使用了一种经修饰的算法(如CRFR1,GIP,mGluR1,GPR24,PTHR1,PTHR2,SCTR,TSHR,VIPR和VIPR2)。这种经修饰的方法主要关注保守的脯氨酸残基(也定位于GPCR的TM6区,接近TM6/IC3交接点),其中该脯氨酸上游的第5个氨基酸通常但不总是苏氨酸残基。对于这些受体,其内源的第5个氨基酸残基是突变的,最优选突变为一个脯氨酸残基。
也可使用其他突变方法(如mGluR1,GPR24和TSHR),相信本领域的普通技术人员有能力选择用于核酸序列突变的技术。重要的是该突变导致组成型活化的受体,基于本文公开的测定组成型活化的多种方式,可在其中使用常规的分析方法。
非内源性已知GPCR的制备优选通过使用Transformer Sited-DirectedTM诱变试剂盒(Stratagene,按商家说明)或QuikeChangeSited-DirectedTM诱变试剂盒(Clontech)。优选使用内源性GPCR为模板,使用两个诱变引物,最优选用赖氨酸诱变寡核苷酸和选择标记寡核苷酸(SEQ.ID.NO.:252,包含在Stratagenen试剂盒中)。为方便起见,引入该已知GPCR的密码子突变和相应的寡核苷酸以标准形式标出(表F):
表F
B、突变的替代方法1、mGluR1
| 受体识别 | 密码子突变 | 5’-3’方向(有义)(SEQ.ID.NO.)突变被下划线 | 5’-3’方向(反义)(SEQ.ID.NO.) |
| 5HT-1A | V343K | CGAGAGAGGAAGACA AAGAAGACGCTGGGCAT(189) | ATGCCCAGCGTCTT CT TTGTCTTCCTCTCTCG(190) |
| 5HT-1B | T313K | GGGAGCGCAAAGCC AAGAAGACCCTAGGGATC(191) | GATCCCTAGGGTCTT C TTGGCTTTGCGCTCCC(192) |
| 5HT-1D | T300K | CGAGAAAGGAAAGCC AAGAAAATCCTGGGCATCATTC(193) | GAATGATGCCCAGGATTTT CTTGGCTTTCCTTTCTCG(194) |
| 5HT-1E | A290K | AGGGAACGGAAGGCA AAACGCATCCTGGGGCT(195) | AGCCCCAGGATGCGTTTTGCCTTCCGTTCCCT(196) |
| 5HT-1F | A292K | CAAGAGAACGGAAAGCA AAGACTACCCTGGGATTAATC(197) | GATTAATCCCAGGGTAGT CTTTGCTTTCCGTTCTCTTG(198) |
| 5HT-2B | S323K | AACGAACAGAGAGCC AAAAAGGTCCTAGGGATTG(199) | CAATCCCTAGGACCTTTTTGGCTCTCTGTTCGTT(200) |
| 5HT-4A | A258K | GGACAGAGACCAAAGCA AAGAAGACCCTGTGCATC(201) | GATGCACAGGGTCTTCTTTGCTTTGGTCTCTGTCC(202) |
| 5HT-4B | A258K | GGACAGAGACCAAAGCA AAGAAGACCCTGTGCATC(203) | GATGCACAGGGTCTTCTTTGCTTTGGTCTCTGTCC(204) |
| 5HT-4C | A258K | GGACAGAGACCAAAGCA AAGAAGACCCTGTGCATC(205) | GATGCACAGGGTCTTCTTTGCTTTGGTCTCTGTCC(206) |
| 5HT-4D | A258K | GGACAGAGACCAAAGCA AAGAAGACCCTGTGCATC(207) | GATGCACAGGGTCTTCTTTGCTTTGGTCTCTGTCC(208) |
| 5HT-4E | A258K | GGACAGAGACCAAAGCA AAGAAGACCCTGTGCATC(209) | GATGCACAGGGTCTTCTTTGCTTTGGTCTCTGTCC(210) |
| 5HT-5A | A284K | AAGGAGCAGCGGGCC AAGCTCATGGTGGGCATC(211) | GATGCCCACCATGAGCTTGGCCCGCTGCTCCTT(212) |
| 5HT-6 | S267K | CTGAAGGCC AAGCTTACGCTGGGCATCCTGCTGGGCA(213) | ATGCCCAGCGTAAGCTTGGC CTTCAGGGCCTTCCTGCT(214) |
| 5HT-7 | A326K | GAACAGAAAGCAAAGACCACCCTGGGGATCATCGT(215) | CCCAGGGTGGTCTTTGCTTTCTGTTCTCGCTTAAA(216) |
| A VPR1A | V290K | GCCAAGATCCGCACGAAG AAGATGACTTTTGTGATCG(217) | CGATCACAAAAGTCAT CTTCTTCGTGCGGATCTTGGC(218) |
| A VPR1B | V280K | GGCCAAGATCCGAACAAAG AAGATGACCTTTGTCATC(219) | CGATGACAAAGGTCAT CTTCTTTGTTCGGATCTTGG CC(220) |
| A VPR2 | V270K | GCTGTGGCCAAGACT AAGAGGATGACGCTAGTG(221) | CACTAGCGTCATCCT C TTAGTCTTGGCCACAGC(222) |
| BBR3 | 270K | CGAAAGAGAATTAAAAGAACGGTATTGGTGTTG(223) | AATACCGTTCT TTTAATTCTCTTTCGGGATTC(224) |
| BDKR1 | T249K | GCCGCAAGGATAGCAAGACC AAAGCGCTGATCCTCAC(225) | GTGAGGATCAGCG CT TTGGTCTTGCTATCCTTGCGGC(226) |
| BDKR2 | T269K | CGGAGAGGAGGGCC AAGGTGCTAGTCCTGGT(227) | ACCAGGACTAGCAC C TTGGCCCTCCTCTCCG(228) |
| C3a | F376K | CGCCAAGTCTCAGAGCAAAACC AAGCGAGTGGCCGTGGTG(229) | CACCACGGCCACTCGCTTGGTTTTGCTCTGAGACTTGGCG(230) |
| C5a | L241K | CGGTCCACCAAGACA AAGAAGGTGGTGGTGGCA(231) | TGCCACCACCACCTT C TTTGTCTTGGTGGACCG(232) |
| CB1 | A342K | CGCATGGACATTAGGTTA AAGAAGACCCTGGTCCTGA(233) | TCAGGACCAGGGTCTT CTTTAACCTAATGTCCATGCG(234) |
| CB2 | A244K | GGCTGGATGTGAGGTTG AAGAAGACCCTAGGGCTAGTG(235) | CACTAGCCCTAGGGTCTT CTTCAACCTCACATCCAGCC(236) |
| CCR2b | V242K | GAAGAGGCATAGGGC AAAGAGAGTCATCTTCACC(237) | GGTGAAGATGACT CT CTTTGCCCTATGCCTCTTC(238) |
| CCR3 | I238K | GTAAAAAAAAGTACAAGGCC AAGCGGCTCATTTTTGTCATC(239) | GATGACAAAAATGAGCCG CTTGGCCTTGTACTTTTTTTTAC(240) |
| CCR5 | V234K | GAAGAGGCACAGGGCT AAGAGGCTTATCTTCACCATC(241) | GATGGTGAAGATAAGCCT CTTAGCCCTGTGCCTCTTC(242) |
| CCR8 | I237K | CCACAACAAGACCAAGGCC AAGAGGTTGGTGCTCATTGTGG(243) | CCACAATGAGCACCAACCT CTTGGCCTTGGTCTTGTTGTGG(244) |
| CCR9 | L253K | TCCAAGCACAAAGCC AAAAAAGTGACCATCACTGTCC(245) | GGACAGTGATGGTCACTTTT TTGGCTTTGTGCTTGGA(246) |
| CRFR1 | T316P | GAAGGCTGTGAAAGCC CCTCTGGTGCTGCTGC(247) | GCAGCAGCACCAG AG GGGCTTTCACAGCCTTC(248) |
| CXCR4 | L238K | AGAAGCGCAAGGCCAAG AAGACCACAGTCATCCTCA(249) | TGAGGATGACTGTGGTCTT CTTGGCCTTGCGCTTCT(250) |
| 多巴胺D1 | L271K | GAGAAACTAAAGTC AAGAAGACTCTGTG(251) | CTCCTTCGGTCCTCCTATCGTTGTCAGAAGT(252) |
| 多巴胺D2 | T372K | GAGAAGAAAGCCAATCAGATGCTCGCC(253) | GGCGAGCATCTGAGTGGCTTTCTTCTC(254) |
| 多巴胺D3 | T328K | GAGAAGAAGGC A AAACAAATGGTGGCC(255) | GGCCACCATTTGTTTTGCCTTCTTCTC(256) |
| 多巴胺D5 | L295K | AAGAAGGAGACCAAAGTT AAAAAGACCCTGTCG(257) | CGACAGGGTCTT TTTAACTTTGGTCTCCTTCTT(258) |
| ETA | A305K | CAGCGTCGAGAAGTG AAAAAAACAGTTTTCTGCTTGGTTGTA(259) | TACAACCAAGCAGAAAACTGTTTT TTTCACTTCTCGACGCTG(260) |
| ETB | A322K | CAGAGACGGGAAGTG AAGAAAACCGTCTTTTGCCTGG(261) | CCAGGCAAAAGACGGTTTT CTTCACTTCCCGTCTCTG(262) |
| FPR1 | L240K | AAGTCCAGTCGTCCC AAACGGGTCCTCTCCTT(263) | AAGGAGAGGACCCG T TTGGGACGACTGGACTT(264) |
| FPRL1 | L240K | AAATCCAGCCGTCCC AAACGGGTCCTCACTGC(265) | GCAGTGAGGACCCG T TTGGGACGGCTGGATTT(266) |
| GALR1 | A246K | CCAAGAAAAAGACT AAACAGACAGTTCTGG(267) | CTCCTTCGGTCCTCCTATCGTTGTCAGAAGT(252) |
| GALR2 | T235K | GCCAAGCGCAAGGTG AAACGCATGATCCTC(268) | GAGGATCATGCG TTTCACCTTGCGCTTGGCG(269) |
| GIP | T343P | AGGCTGGCTCGCTCC CCGCTGACGCTGGTGC(270) | GCACCAGCGTCAG CG GGGAGCGAGCCAGCCT(271) |
| MGluR1 | 3’缺失 | 参见下述替代方法 | 参见下述替代方法 |
| GPR5 | V224K | CGGCGCCACCGCACG AAAAAGCTCATCTTC(272) | CTCCTTCGGTCCTCCTATCGTTGTCAGAAGT(252) |
| GPR24(也被称为MCH或SLC-1) | T255KT255K/T257R24-IC3-SST2C305YP271LW269CW269FW269LF265II261QD140N | 参见下述替代方法 | 参见下述替代方法 |
| GRPR | A263K | GGAAGCGACTT A AGAAGACAGTGCTGGTGTTT(273) | CAGCACTGTCTT CTTAAGTCGCTTCCGGGATTC(274) |
| M1 | A364K | AAGGAGAAGAAGGCG AAACGGACCCTGAGTGCC(275) | GGCACTCAGGGTCCGTTTCGCCTTCTTCTCCTT(276) |
| M2 | T386K | CCGGGAAAAGAAAGTC AAGAGGACAATCTTGGCT(277) | AGCCAAGATTGTCCTCTTGACTTTCTTTTCCCGG(278) |
| M3 | A490K | GGTCAAGGAGAAGAAAGCG AAACAGACCCTCAGTGCG(279) | CGCACTGAGGGTCTGTTTCGCTTTCTTCTCCTTGACC(280) |
| M4 | T399K | GGGAGCGCAAAGTG AAACGAACGATCTTTGCC(281) | GGCAAAGATCGTTCGTTTCACTTTGCGCTCCC(282) |
| M5 | A441K | GTCAAAGAGAGGAAAGC AAAACAGACACTGAGTGCC(283) | GGCACTCAGTGTCTG T TTTGCTTTCCTCTCTTTGAC(284) |
| MC3 | A241K | GCAACACTCATGTATGAAGGGG AAAGTCACCATCACC(285) | CTCCTTCGGTCCTCCTATCGTTGTCAGAAGT(252) |
| NK1R | V247K | GCCAAGCGCAAGGTG AAGAAAATGATGATTGTC(286) | GACAATCATCATTTT C TTCACCTTGCGCTTGGC(287) |
| NK2R | V249K | GCCAAGAAGAAGTTT AAGAAGACCATGGTGCT(288) | AGCACCATGGTCTT CT TAAACTTCTTCTTGGC(289) |
| NK3R | V298K | GGCCAAAAGAAAGGTT AAGAAAATGATGATTATTG(290) | CAATAATCATCATTTTCTTAACCTTTCTTTTGGCC(291) |
| NMBR | A265K | CACGGAAACGCCTG AAAAAAATTGTGCTTG(292) | CAAGCACAATTTT TTTCAGGCGTTTCCGTG(293) |
| NPY5 | F367K | GAATAAAAAAGAGATCACG AAGTGTTAAGTACAGACTGACC(294) | GGTCAGTCTGTA CTTAACACTTCGTGATCTCTTTTTTAT(295) |
| NTSR1 | V302K | GCCCTGCGGCACGGC AAGCGCGTCCTACGTGC(296) | GCACGTAGGACGCG C TTGCCGTGCCGCAGGGC(297) |
| NTSR2 | V269K | AGCCTCCAGCGCAGCAAGCAGGTTCTCAGAGCC(298) | GGCTCTGAGAACCTGCTTGCTGCGCTGGAGGCT(299) |
| OPRD | T260K | GCCTGCGGCGCATC AAGCGCATGGTGCTGGT(300) | ACCAGCACCATGCG C TTGATGCGCCGCAGGC(301) |
| OPRL1 | T262K | ACCTGCGGCGCATC AAGCGGCTGGTGCTGGTG(302) | CACCAGCACCAGCCGCTTGATGCGCCGCAGGT(303) |
| OPRK | T273K | ACCTGCGTAGGATC AAGAGACTGGTCCTGGTG(304) | CACCAGGACCAGTCTCTTGATCCTACGCAGGT(305) |
| OPRM | T281K | GGGAATCTTCGAAGGATC AAGAGGATGGTGCTGGTG(306) | CACCAGCACCATCCTCTTGATCCTTCGAAGATTCC(307) |
| OPRM1A | T281K | GGGAATCTTCGAAGGATC AAGAGGATGGTGCTGGTG(308) | CACCAGCACCATCCTCTTGATCCTTCGAAGATTCC(309) |
| OX1R | A297K | CGGAGGAAGAC A AAAAAGATGCTGATGG(310) | CCATCAGCATCTT TTTTGTCTTCCTCCG(311) |
| OX2R | A303K | CCAGAAGGAAAACA AAACGGATGTTGATG(312) | CTCCTTCGGTCCTCCTATCGTTGTCAGAAGT(252) |
| PACAP | T355K | CGACTGGCCCGGTCC CCCCTGCTGCTCATCC(313) | GGATGAGCAGCAG GG GGGACCGGGCCAGTCG(314) |
| PAF | L231K | GTCAAGCGCCGGGCG AAGTGGATGGTGTGCAC(315) | GTGCACACCATCCA C TTCGCCCGGCGCTTGAC(316) |
| PGE EP1 | V296K | CACGACGTGGAGATG AAGGGCCAGCTTGTCGG(317) | CCGACAAGCTGGCC C TTCATCTCCACGTCGTG(318) |
| PGE EP2 | L263K | GAGGAGACGGACCAC AAGATTCTCCTGGCTATCATG(319) | CATGATAGCCAGGAGAAT CTTGTGGTCCGTCTCCTC(320) |
| PGE EP4 | V271K | GCCGAGATCCAGATG AAGATCTTACTCATTGCCACC(321) | GGTGGCAATGAGTAAGAT CTTCATCTGGATCTCGGC(322) |
| PTHR1 | T410P | GGAAGCTGCTCAAATCCCCGCTGGTGCTCATGC(323) | GCATGAGCACCAGCGGGGATTTGAGCAGCTTCC(324) |
| PTHR2 | T365P | GGAAACTGGCCAAATCG CCACTGGTCCTGGTCC(325) | GGACCAGGACCAG TG GCGATTTGGCCAGTTTCC(326) |
| SCTR | T344P | CGCCTGGCCAGGTCC CCTCTCCTGCTGATCC(327) | GGATCAGCAGGAG AG GGGACCTGGCCAGGCG(328) |
| SST1 | T270K | CGAGCGCAAGATC AAATTAATGGTGATGG(329) | CTCCTTCGGTCCTCCTATCGTTGTCAGAAGT(252) |
| SST2 | T255K | AGAAGAAGGTC A AACGAATGGTGTCCATCGTG(330) | GGACACCATTCG TTTGACCTTCTTCTCAGACT(331) |
| SST3 | T256K | GAACGCAGGGTCAAGCGCATGGTGGTGGCC(332) | CTCCTTCGGTCCTCCTATCGTTGTCAGAAGT(252) |
| SST4 | T258K | CGGAGAAGAAAATCA AAAGGCTGGTGCTG(333) | CTCCTTCGGTCCTCCTATCGTTGTCAGAAGT(252) |
| SST5 | T247K | TCGGAGCGAAAGGTG AAGCGCATGGTGTTGGTGGT(334) | ACCATGCG CTTCACCTTTCGCTCCGAGCGCCGCCG(335) |
| TSHR | V509AD619GA623IA623KC672YD619G/A623KV509A/C672YV509A/A623K/C672Y | 参见下述替代方法 | 参见下述替代方法 |
| VIPR | T343P | AGGCTAGCCAGGTCC CCACTCCTGCTGATCC(336) | GGATCAGCAGGAG TG GGGACCTGGCTAGCCT(337) |
| VIPR2 | T330P | AGGCTGGCCAAGTCCC CGCTCCTGCTTATCC(338) | GGATAAGCAGGAG CG GGGACTTGGCCAGCCT(339) |
非内源性人mGluR1受体变体的制备是通过将3’末端的细胞内区域的一部分缺失而实现的。这种内源性人mGluR1使用一模板和有缓冲系统的rTth聚合酶(Perkin Elmer)进行PCR而获得,缓冲液系统由生产商提供。第一轮PCR的循环条件如下:30次循环的94℃1分钟,65℃1分钟,72℃1分50秒。包含SalI位点的5’PCR片段是利用海马DNA为模板,和以下引物对
5’-GCAGGCTGTCGACCTCGTCCTCACCACCATGGTC-3’(SEQ.ID.NO.:340)和
5’-AATGGGCTCACAGCCTGTTAGATCTGCATTGGGCCAC-3’(SEQ.ID.NO.:341)获得的。
中间PCR片段利用基因组DNA为模板获得,循环条件是:30次循环的94℃1分钟,65℃1分钟,72℃1分50秒,引物对为:5’-GCAGGCTGTCGACCTCGTCCTCACCACCATGGTC-3’(SEQ.ID.NO.:342)和
5’-AATGGGCTCACAGCCTGTTAGATCTGCATTGGGCCAC-3’(SEQ.ID.NO.:343)。
3’PCR片段是利用内源mGluR1克隆体为共模板,用pfu聚合酶获得全长cDNA。该PCR反应的循环条件是:30次循环的94℃1分钟,65℃2分30秒,72℃1分30秒,引物对为:5’-TGCGAATTCTAATGGCAAGTCTGTGTCATGGTC-3’(SEQ.ID.NO.:344)和
5’-TGCGGATCCTCTTCGGAAGATGTTGAGGAAAGTG-3’(SEQ.ID.NO.:345)(核酸序列参见SEQ.ID.NO.:346,氨基酸序列参见SEQ.ID.NO.:347)。2、GPR24(MCH或SLC-1)
非内源性人GPR24受体变体的制备是通过制造以下突变而实现的:T255K突变(核酸序列参见SEQ.ID.NO.:350,氨基酸序列参见SEQ.ID.NO.:351),T255K/T257R突变(核酸序列参见SEQ.ID.NO.:354,氨基酸序列参见SEQ.ID.NO.:355),24-IC3-SST3突变(核酸序列参见SEQ.ID.NO.:358,氨基酸序列参见SEQ.ID.NO.:359),C305Y突变(核酸序列参见SEQ.ID.NO.:362,氨基酸序列参见SEQ.ID.NO.:363),P271L突变(核酸序列参见SEQ.ID.NO.:366,氨基酸序列参见SEQ.ID.NO.:367),W269C突变(核酸序列参见SEQ.ID.NO.:370,氨基酸序列参见SEQ.ID.NO.:371),W269F突变(核酸序列参见SEQ.ID.NO.:374,氨基酸序列参见SEQ.ID.NO.:375),W269L突变(核酸序列参见SEQ.ID.NO.:378,氨基酸序列参见SEQ.ID.NO.:379),F265I突变(核酸序列参见SEQ.ID.NO.:382,氨基酸序列参见SEQ.ID.NO.:383),I261Q突变(核酸序列参见SEQ.ID.NO.:386,氨基酸序列参见SEQ.ID.NO.:387),和D140N突变(核酸序列参见SEQ.ID.NO.:390,氨基酸序列参见SEQ.ID.NO.:391)。A、T255K突变
非内源性人GPR24受体变体是通过制造一个T255K突变而实现的(核酸序列参见SEQ.ID.NO.:350,氨基酸序列参见SEQ.ID.NO.:351)。按商家说明用Transformer Sited-DirectedTM诱变试剂盒(Clontech)进行诱变。使用的PCR有义诱变引物序列如下:5’-AGAGGGTG
AAACGCACAGCCATCGCCATCTG-3’(SEQ.ID.NO.:348),反义引物(选择标记)序列如下:
5’-CTCCTTCGGTCCTCCTATCGTTGTCAGAAGT-3’(SEQ.ID.NO.:349)。
内源性GPR24 cDNA被用做模板。B、T255K/T257R突变
非内源性人GPR24受体变体是通过制造一个T255K/T257R突变而实现的(核酸序列参见SEQ.ID.NO.:354,氨基酸序列参见SEQ.ID.NO.:355)。按商家说明用QuickChange Sited-DirectedTM诱变试剂盒(Stratagene)进行诱变。使用的PCR有义诱变引物序列如下:5’-AGAGGGTG
AAACGCAGAGCCATCGCCATCTG-3’(SEQ.ID.NO.:352),反义引物序列如下:
5’-CAGATGGCGATGGC
TCTGCG
TTTCACCCTCT-3’(SEQ.ID.NO.:353)。
内源性GPR24 cDNA被用做模板。C、24-IC3-SST2突变
非内源性人GPR24受体的变体是通过制造一个24-IC3-SST2突变而实现的(核酸序列参见SEQ.ID.NO.:358,氨基酸序列参见SEQ.ID.NO.:359)。Blast的结果显示GPR24对SST2有最高的序列同源性。因此,用SST2的IC3环替代GPR24的IC3环,以确定这种嵌合体是否可表现组成型活性。
包含GPR24 IC3的BamHI-BstEII片段用包含SST2 IC3的合成寡核苷酸片段替代。使用的PCR有义诱变引物序列如下:5’-GATCCTGCAGAAGGTGAAGTCCTCTGGAATCCGAGTGGGCTCCTCTAAGAGGAAGAAGTCTGAGAAGAAG-3’(SEQ.ID.NO.:356),反义引物序列如下:
5’-GTGACCTTCTTCTCAGACTTCTTCCTCTTAGAGGAGCCCACTCGGATTCCAGAGGACTTCACCTTCTGCAG-3’(SEQ.ID.NO.:357)。
内源性GPR24 cDNA被用做模板。D、C305Y突变
非内源性人GPR24受体的变体是通过制造一个C305Y突变而实现的(核酸序列参见SEQ.ID.NO.:362,氨基酸序列参见SEQ.ID.NO.:363)。按商家说明用QuickChange Sited-DirectedTM诱变试剂盒(Stratagene)进行诱变。使用的PCR有义诱变引物序列如下:5’-GGCTATGCCAACAGC
TACCTCAACCCCTTTGTG-3’(SEQ.ID.NO.:360),反义引物序列如下:
5’-CACAAAGGGGTTGAG
GTAGCTGTTGGCATAGCC-3’(SEQ.ID.NO.:361)。
内源性GPR24 cDNA被用做模板。E、P271L突变
非内源性人GPR24受体的变体是通过制造一个P271L突变而实现的(核酸序列参见SEQ.ID.NO.:366,氨基酸序列参见SEQ.ID.NO.:367)。按商家说明用QuickChange Sited-DirectedTM诱变试剂盒(Stratagene)进行诱变。使用的PCR有义诱变引物序列如下:5’-TTGTGTGCTGGGCA
CTCTACTATGTGCTACAGC-3’(SEQ.ID.NO.:364),反义引物序列如下:
5’-GCTGTAGCACATAGTA
GAGTGCCCAGCACACAA-3’(SEQ.ID.NO.:365)。
内源性GPR24 cDNA被用做模板。F、W269C突变
非内源性人GPR24受体的变体是通过制造一个W269C突变而实现的(核酸序列参见SEQ.ID.NO.:370,氨基酸序列参见SEQ.ID.NO.:371)。按商家说明用QuickChange Sited-DirectedTM诱变试剂盒(Stratagene)进行诱变。使用的PCR有义诱变引物序列如下:5’-GGTCTTCTTTGTGTGC
TGCGCACCCTACTATGTG-3’(SEQ.ID.NO.:368),反义引物序列如下:
5’-CACATAGTAGGGTGC
GCAGCACACAAAGAAGACC-3’(SEQ.ID.NO.:369)。
内源性GPR24 cDNA被用做模板。G、W269F突变
非内源性人GPR24受体的变体是通过制造一个W269F突变而实现的(核酸序列参见SEQ.ID.NO.:374,氨基酸序列参见SEQ.ID.NO.:375)。按商家说明用QuickChange Sited-DirectedTM诱变试剂盒(Stratagene)进行诱变。使用的PCR有义诱变引物序列如下:5’-GGTCTTCTTTGTGTGC
TTCGCACCCTACTATGTG-3’(SEQ.ID.NO.:372),反义引物序列如下:
5’-CACATAGTAGGGTGC
GAAGCACACAAAGAAGACC-3’(SEQ.ID.NO.:373)。
内源性GPR24 cDNA被用做模板。H、W269L突变
非内源性人GPR24受体的变体是通过制造一个W269L突变而实现的(核酸序列参见SEQ.ID.NO.:378,氨基酸序列参见SEQ.ID.NO.:379)。按商家说明用QuickChange Sited-DirectedTM诱变试剂盒(Stratagene)进行诱变。使用的PCR有义诱变引物序列如下:5’-GGTCTTCTTTGTGTGC
TTGGCACCCTACTATGTG-3’(SEQ.ID.NO.:376),反义引物序列如下:
5’-CACATAGTAGGGTGC
CAAGCACACAAAGAAGACC-3’(SE Q.ID.NO.:377)。
内源性GPR24 cDNA被用做模板。I、F265I突变
非内源性人GPR24受体的变体是通过制造一个F265I突变而实现的(核酸序列参见SEQ.ID.NO.:382,氨基酸序列参见SEQ.ID.NO.:383)。按商家说明用QuickChange Sited-DirectedTM诱变试剂盒(Stratagene)进行诱变。使用的PCR有义诱变引物序列如下:5’-GCCATCTGTCTGGTC
ATCTTTGTGTGCTGGG-3’(SEQ.ID.NO.:380),反义引物序列如下:
5’-CCCAGCACACAAA
GATGACCAGACAGATGGC-3’(SEQ.ID.NO.:381)。
内源性GPR24 cDNA被用做模板。J、I261Q突变
非内源性人GPR24受体的变体是通过制造一个I261Q突变而实现的(核酸序列参见SEQ.ID.NO.:386,氨基酸序列参见SEQ.ID.NO.:387)。按商家说明用QuickChange Sited-DirectedTM诱变试剂盒(Stratagene)进行诱变。使用的PCR有义诱变引物序列如下:5’-CGCACAGCCATCGCC
CAGTGTCTGGTCTTCTTTGTG-3’(SEQ.ID.NO.:384),反义引物序列如下:
5’-CACAAAGAAGACCAGACA
CTGGGCGATGGCTGTGCG-3’(SEQ.ID.NO.:385)。
内源性GPR24 cDNA被用做模板。K、D140N突变
非内源性人GPR24受体的变体是通过制造一个D140N突变而实现的(核酸序列参见SEQ.ID.NO.:390,氨基酸序列参见SEQ.ID.NO.:391)。按商家说明用QuikChange Sited-DiTectedTM诱变试剂盒(Stratagene)进行诱变。使用的PCR有义诱变引物序列如下:5’-ACCGCCATGGCCATT
AACGCGTACCTGGCCACT-3’(SEQ.ID.NO.:388),反义引物序列如下:
5’-AGTGGCCAGGTAGCG
GTTAATGGCCATGGCGGT-3’(SEQ.ID.NO.:389)。
内源性GPR24 cDNA被用做模板。3、TSHR
非内源性人TSHR受体是通过制造以下突变而实现:V509A突变(核酸序列参见SEQ.ID.NO.:394,氨基酸序列参见SEQ.ID.NO.:395),D619G突变(核酸序列参见SEQ.ID.NO.:398,氨基酸序列参见SEQ.ID.NO.:399),A623I突变(核酸序列参见SEQ.ID.NO.:402,氨基酸序列参见SEQ.ID.NO.:403),A623K突变(核酸序列参见SEQ.ID.NO.:406,氨基酸序列参见SEQ.ID.NO.:407),C672Y突变(核酸序列参见SEQ.ID.NO.:410,氨基酸序列参见SEQ.ID.NO.:411),D619G/A623K突变(核酸序列参见SEQ.ID.NO.:414,氨基酸序列参见SEQ.ID.NO.:415),V509A/C672Y突变(核酸序列参见SEQ.ID.NO.:418,氨基酸序列参见SEQ.ID.NO.:419)和V509A/A623K/C672Y突变(核酸序列参见SEQ.ID.NO.:422,氨基酸序列参见SEQ.ID.NO.:423)。A、V509A突变
非内源性人TSHR受体的变体是通过制造一个V509A突变而实现的(核酸序列参见SEQ.ID.NO.:394,氨基酸序列参见SEQ.ID.NO.:395)。按商家说明用QuikChange Sited-DirectedTM诱变试剂盒(Stratagene)进行诱变。使用的PCR有义诱变引物序列如下:5’-CAAGCGAGTTATCG
GCATATACGCTGACGGTC-3’(SEQ.ID.NO.:392),反义引物序列如下:
5’-GACCGTCAGCGTATA
TGCCGATAACTCGCTTG-3’(SEQ.ID.NO.:393)。
内源性TSHR cDNA被用做模板。这种V509A突变体可通过在突变位点附近AccI位点的缺失而与其内源形式区分开。B、D619G突变
非内源性人TSHR受体的变体是通过制造一个D619G突变而实现的(核酸序列参见SEQ.ID.NO.:398,氨基酸序列参见SEQ.ID.NO.:399)。按商家说明用QuikChange Sited-DirectedTM诱变试剂盒(Stratagene)进行诱变。使用的PCR有义诱变引物序列如下:5’-ACCCAGGGGACAAA
GGTACCAAAATTGCCAA-3’(SEQ.ID.NO.:396),反义引物(选择标记)序列如下:5’-TTGGCAATTTTGGT
ACCTTTGTCCCCTGGGT-3’(SEQ.ID.NO.:397)。
内源性TSHR cDNA被用做模板。这种D619G突变体可通过在突变位点附近KpnI位点的出现而与其内源形式区分开。C、A623I突变
非内源性人TSHR受体的变体是通过制造一个A623I突变而实现的(核酸序列参见SEQ.ID.NO.:402,氨基酸序列参见SEQ.ID.NO.:403)。按商家说明用QuikChange Sited-DirectedTM诱变试剂盒(Stratagene)进行诱变。使用的PCR有义诱变引物序列如下:5’-AAAGATACCAAAATT
ATCAAGAGGATGGCTGT-3’(SEQ.ID.NO.:400),反义引物序列如下:
5’-ACAGCCATCCTCTT
GATAATTTTGGTATCTTT-3’(SEQ.ID.NO.:401)。
内源性TSHR cDNA被用做模板。这种A623I突变体可通过在突变位点附近BstXI位点的缺失而与其内源形式区分开。D、A623K突变
非内源性人TSHR受体的变体是通过制造一个A623K突变而实现的(核酸序列参见SEQ.ID.NO.:406,氨基酸序列参见SEQ.ID.NO.:407)。按商家说明用QuikChange Sited-DirectedTM诱变试剂盒(Stratagene)进行诱变。使用的PCR有义诱变引物序列如下:5’-AAAGATACCAAAATT
AAGAAGAGGATGGCTGTG-3’(SEQ.ID.NO.:404),反义引物序列如下:
5’-CACAGCCATCCTCTT
CTTAATTTTGGTATCTTT-3’(SEQ.ID.NO.:405)。
内源性TSHR cDNA被用做模板。这种A623K突变体可通过在突变位点附近BstXI位点的缺失而与其内源形式区分开。E、C672Y突变
非内源性人TSHR受体的变体是通过制造一个C672Y突变而实现的(核酸序列参见SEQ.ID.NO.:410,氨基酸序列参见SEQ.ID.NO.:411)。按商家说明用QuikChange Sited-DirectedTM诱变试剂盒(Stratagene)进行诱变。使用的PCR有义诱变引物序列如下:5’-CTATCCACTTAACTCG
TACGCCAATCCATTCCTC-3’(SEQ.ID.NO.:408),反义引物序列如下:
5’-GAGGAATGGATTGGC
GTACGAGTTAAGTGGATGA-3’(SEQ.ID.NO.:409)。
内源性TSHR cDNA被用做模板。这种C672Y突变体可通过在突变位点附近BsiWI位点的存在而与其内源形式区分开。F、D619G/A623K突变
非内源性人TSHR受体是通过制造一个D619G/A623K突变而实现的(核酸序列参见SEQ.ID.NO.:414,氨基酸序列参见SEQ.ID.NO.:415)。按商家说明用QuikChange Sited-DirectedTM诱变试剂盒(Stratagene)进行诱变。使用的PCR有义诱变引物序列如下:5’-ACCCAGGGGACAAA
GGTACCAAAATT
AAGAAGAGGATGGCTGTG-3’(SEQ.ID.NO.:412),反义引物序列如下:5’-CACAGCCATCCTCTT
CTTAATTTTGGT
ACCTTTGTCCCCTGGGT-3’(SEQ.ID.NO.:413)。
内源性TSHR cDNA的D619G形式被用做模板。这种D619G/A623K突变体可通过在D619G突变位点附近KpnI位点的出现和在A623K突变位点附近BstXI位点的缺失而与其内源形式区分开。G、V509A/C672Y突变
非内源性人TSHR受体的变体是通过制造一个V509A/C672Y突变而实现的(核酸序列参见SEQ.ID.NO.:418,氨基酸序列参见SEQ.ID.NO.:419)。按商家说明用QuikChange Sited-DirectedTM诱变试剂盒(Stratagene)进行诱变。使用的V509A有义诱变引物序列如下:5’-CAAGCGAGTTATCGGCATATACGCTGACGGTC-3’(SEQ.ID.NO.:416),C672Y反义引物序列如下:
5’-GAGGAATGGATTGGCGTACGAGTTAAGTGGATAG-3’(SEQ.ID.NO.:417)。
内源性TSHR cDNA被用做模板。这种A509A/C672Y突变体可通过在V509A突变位点附近AccI位点的缺失和在C672Y突变位点附近BsiWI位点的出现而与其内源形式区分开。H、V509A/A623K/C672Y突变
非内源性人TSHR受体的变体是通过制造一个V509A/A623K/C672Y突变而实现的(核酸序列参见SEQ.ID.NO.:422,氨基酸序列参见SEQ.ID.NO.:423)。按商家说明用QuikChange Sited-DirectedTM诱变试剂盒(Stratagene)进行诱变。使用的A623K有义诱变引物序列如下:5’-AAAGATACCAAAATTAAGAAGAGGATGGCTGTG-3’(SEQ.ID.NO.:420),A623K反义引物(选择标记)序列如下:5’-CACAGCCATCCTCTTCTTAATTTTGGTATCTTT-3’(SEQ.ID.NO.:421)。
TSHR cDNA的内源性V509A/C672Y突变体被用做模板。这种V509A/A623K/C672Y突变体可通过在V509A突变位点附近AccI位点的缺失、A623K突变位点附近BstXI的缺失以及在C672Y突变位点附近BsiWI位点的出现而与其内源形式区分开。
然后可对这些非内源的人GPCR进行测序,衍生出并经证实的核苷酸和氨基酸序列列于本专利文件所附的“序列表”中,如下表G所总结的:
表G
| 突变的GPCR | 核酸序列 | 氨基酸序列 |
| 5HT-1AV343K | SEQ.ID.NO.:424 | SEQ.ID.NO.:425 |
| 5HT-1BT313K | SEQ.ID.NO.:426 | SEQ.ID.NO.:427 |
| 5HT-1DT300K | SEQ.ID.NO.:428 | SEQ.ID.NO.:429 |
| 5HT-1EA290K | SEQ.ID.NO.:430 | SEQ.ID.NO.:431 |
| 5HT-1FA292K | SEQ.ID.NO.:432 | SEQ.ID.NO.:433 |
| 5HT-2BS323K | SEQ.ID.NO.:434 | SEQ.ID.NO.:435 |
| 5HT-4AA258K | SEQ.ID.NO.:436 | SEQ.ID.NO.:437 |
| 5HT-4BA258K | SEQ.ID.NO.:438 | SE Q.ID.NO.:439 |
| 5HT-4CA258K | SEQ.ID.NO.:440 | SEQ.ID.NO.:441 |
| 5HT-4DA258K | SEQ.ID.NO.:442 | SEQ.ID.NO.:443 |
| 5HT-4EA258K | SEQ.ID.NO.:444 | SEQ.ID.NO.:445 |
| 5HT-5AA284K | SEQ.ID.NO.:446 | SEQ.ID.NO.:447 |
| 5HT-6S267K | SEQ.ID.NO.:448 | SEQ.ID.NO.:449 |
| 5HT-7A326K | SEQ.ID.NO.:450 | SE Q.ID.NO.:451 |
| A VPR1AV290K | SEQ.ID.NO.:452 | SE Q.ID.NO.:453 |
| A VPR1BV280K | SEQ.ID.NO.:454 | SEQ.ID.NO.:455 |
| A VPR2V270K | SEQ.ID.NO.:456 | SEQ.ID.NO.:457 |
| BBR3A270K | SEQ.ID.NO.:458 | SEQ.ID.NO.:459 |
| BDKR1T249K | SEQ.ID.NO.:460 | SEQ.ID.NO.:461 |
| BDKR2T269K | SEQ.ID.NO.:462 | SEQ.ID.NO.:463 |
| C3aF376K | SEQ.ID.NO.:464 | SEQ.ID.NO.:465 |
| C5aL241K | SEQ.ID.NO.:466 | SEQ.ID.NO.:467 |
| CB1A342K | SEQ.ID.NO.:468 | SEQ.ID.NO.:469 |
| CB2A244K | SEQ.ID.NO.:470 | SEQ.ID.NO.:471 |
| CCR2bV242K | SEQ.ID.NO.:472 | SEQ.IID.NO.:473 |
| CCR3I238K | SEQ.ID.NO.:474 | SEQ.ID.NO.:475 |
| CCR5V234K | SEQ.ID.NO.:476 | SEQ.ID.NO.:477 |
| CCR8I237K | SEQ.ID.NO.:478 | SEQ.ID.NO.:479 |
| CCR9L253K | SEQ.ID.NO.:480 | SEQ.ID.NO.:481 |
| CRFR1T316P | SEQ.ID.NO.:482 | SEQ.ID.NO.:483 |
| CXCR4L238K | SEQ.ID.NO.:484 | SEQ.ID.NO.:485 |
| 多巴胺D1L271K | SEQ.ID.NO.:486 | SEQ.ID.NO.:487 |
| 多巴胺D2T372K | SEQ.ID.NO.:488 | SEQ.ID.NO.:489 |
| 多巴胺D3T328K | SEQ.ID.NO.:490 | SEQ.ID.NO.:491 |
| 多巴胺D5L295K | SEQ.ID.NO.:492 | SEQ.ID.NO.:493 |
| ETAA305K | SEQ.ID.NO.:494 | SEQ.ID.NO.:495 |
| ETBA322K | SEQ.ID.NO.:496 | SEQ.ID.NO.:497 |
| FPR1L240K | SEQ.ID.NO.:498 | SEQ.ID.NO.:499 |
| FPRL1L240K | SEQ.ID.NO.:500 | SEQ.ID.NO.:501 |
| GALR1A246K | SEQ.ID.NO.:502 | SEQ.ID.NO.:503 |
| GALR2T235K | SEQ.ID.NO.:504 | SEQ.ID.NO.:505 |
| GIPT343P | SEQ.ID.NO.:506 | SEQ.ID.NO.:507 |
| mGluR13’缺失 | SEQ.ID.NO.:346 | SEQ.ID.NO.:347 |
| GPR5V244K | SEQ.ID.NO.:508 | SEQ.ID.NO.:509 |
| GPR24(也被称为MCH或SLC-1) | SEQ.ID.NO.:350SEQ.ID.NO.:354SEQ.ID.NO.:358SEQ.ID.NO.:362SEQ.ID.NO.:366SEQ.ID.NO.:370SEQ.ID.NO.:374SEQ.ID.NO.:378SEQ.ID.NO.:382SEQ.ID.NO.:386SEQ.ID.NO.:390 | SEQ.ID.NO.:351SEQ.ID.NO.:355SEQ.ID.NO.:359SEQ.ID.NO.:363SEQ.ID.NO.:367SEQ.ID.NO.:371SEQ.ID.NO.:375SEQ.ID.NO.:379SEQ.ID.NO.:383SEQ.ID.NO.:387SEQ.ID.NO.:391 |
| T255KT255K/T257R24-IC3-SST2C305YP271LW269CW269FW269LF265II261QD140N | ||
| GRPRA263K | SEQ.ID.NO.:510 | SEQ.ID.NO.:511 |
| M1A364K | SEQ.ID.NO.:512 | SEQ.ID.NO.:513 |
| M2T386K | SEQ.ID.NO.:514 | SEQ.ID.NO.:515 |
| M3A490K | SEQ.ID.NO.:516 | SEQ.ID.NO.:517 |
| M4T399K | SEQ.ID.NO.:518 | SEQ.ID.NO.:519 |
| M5A441K | SEQ.ID.NO.:520 | SEQ.ID.NO.:521 |
| MC3A241K | SEQ.ID.NO.:522 | SEQ.ID.NO.:523 |
| NK1RV247K | SEQ.ID.NO.:524 | SEQ.ID.NO.:525 |
| NK2R | SEQ.ID.NO.:526 | SEQ.ID.NO.:527 |
| V249K | ||
| NK3RV298K | SEQ.ID.NO.:528 | SEQ.ID.NO.:529 |
| NMBRA265K | SEQ.ID.NO.:530 | SEQ.ID.NO.:531 |
| NPY5A297K | SEQ.ID.NO.:532 | SEQ.ID.NO.:533 |
| NTSR1V302K | SEQ.ID.NO.:534 | SEQ.ID.NO.:535 |
| NTSR2V269K | SEQ.ID.NO.:536 | SEQ.ID.NO.:537 |
| OPRDT260K | SEQ.ID.NO.:538 | SEQ.ID.NO.:539 |
| OPRL1T262K | SEQ.ID.NO.:540 | SEQ.ID.NO.:541 |
| OPRKT273K | SEQ.ID.NO.:542 | SEQ.ID.NO.:543 |
| OPRMT281K | SEQ.ID.NO.:544 | SEQ.ID.NO.:545 |
| OPRM1AT281K | SEQ.ID.NO.:546 | SEQ.ID.NO.:547 |
| OX1RF367K | SEQ.ID.NO.:548 | SEQ.ID.NO.:549 |
| OX2RA297K | SEQ.ID.NO.:550 | SEQ.ID.NO.:551 |
| PACAPT355K | SEQ.ID.NO.:552 | SEQ.ID.NO.:553 |
| PAFL231K | SEQ.ID.NO.:554 | SEQ.ID.NO.:555 |
| PGE EP1V296K | SEQ.ID.NO.:556 | SEQ.ID.NO.:557 |
| PGE EP2L263K | SEQ.ID.NO.:558 | SEQ.ID.NO.:559 |
| PGE EP4V271K | SEQ.ID.NO.:560 | SEQ.ID.NO.:561 |
| PTHR1T410P | SEQ.ID.NO.:562 | SEQ.ID.NO.:563 |
| PTHR2T365P | SEQ.ID.NO.:564 | SEQ.ID.NO.:565 |
| SCTR | SEQ.ID.NO.:566 | SEQ.ID.NO.:567 |
| T344P | ||
| SST1T290K | SEQ.ID.NO.:568 | SEQ.ID.NO.:569 |
| SST2T255K | SEQ.ID.NO.:570 | SEQ.ID.NO.:571 |
| SST3T256K | SEQ.ID.NO.:572 | SEQ.ID.NO.:573 |
| SST4T258K | SEQ.ID.NO.:574 | SEQ.ID.NO.:575 |
| SST5T247K | SEQ.ID.NO.:576 | SEQ.ID.NO.:577 |
| TSHR | SEQ.ID.NO.:394SEQ.ID.NO.:398SEQ.ID.NO.:402SEQ.ID.NO.:406SEQ.ID.NO.:410SEQ.ID.NO.:414SEQ.ID.NO.:418SEQ.ID.NO.:422 | SEQ.ID.NO.:395SEQ.ID.NO.:399SEQ.ID.NO.:403SEQ.ID.NO.:407SEQ.ID.NO.:411SEQ.ID.NO.:415SEQ.ID.NO.:419SEQ.ID.NO.:423 |
| V509AD619GA623IA623KC672YD619G/A623KV509A/C672YV509A/A623K/C672Y | ||
| VIPRT343P | SEQ.ID.NO.:578 | SEQ.ID.NO.:579 |
| VIPR2T330P | SEQ.ID.NO.:580 | SEQ.ID.NO.:581 |
可对已知GPCRs的这些非内源形式的组成型活性进行评估。实施例3受体表达
尽管在本领域中有多种细胞可用于蛋白质的表达,但最优选应用的是哺乳动物细胞。据预测,其基本原因是实用性,即例如表达GPCR的酵母细胞的应用,有可能把一种非哺乳动物细胞引入到程序中,此细胞可能不(其实,对于酵母来说,是不)包括偶联受体、遗传机制和分泌途径,而这些是经过进化用于哺乳动物系统的。因此,在非哺乳动物细胞中得到的结果,尽管是可能有用的,但并不如从哺乳动物细胞中得到的结果优选。在哺乳动物细胞中,COS-7、Hek-293和Hek-293T细胞是特别优选的,尽管应用的特定哺乳动物细胞是根据技术人员的特别需要。以下的方法用于指定的受体,也可用于本文所公开的其他受体。
第一天,将2×104个Hek-293T细胞铺平板。第二天,准备两支试管(比例是每板用于一支试管):通过混合20μg DNA(例如pCMV载体、带有受体cDNA的pCMV载体,等)在1.2ml无血清的DMEM(IrvineScientific,Irvine,CA)来制备试管A;通过混合120μl lipofectamine(Gibco BRL)在1.2ml无血清DMEM中制备试管B。把试管A和B互倾混合(几次),然后在室温下孵育30-45分钟。该混合物被称为“转染混合物”。铺板的Hek-293T细胞用1XPBS洗涤,然后加入10ml无血清的DMEM。把2.4ml转染混合物加入到细胞中去,然后在37℃/5%CO2下温育4小时。接着通过抽吸移去转染混合物,然后加入25ml的DMEM/10%胎牛血清。接着细胞在37℃/5%CO2温育。72小时后收获细胞并用来进行分析。实施例4测定非内源GPCRs组成型活性的试验
多种方法可用来评估非内源人GPCRs的组成型活性,下面的举例是说明性的;本领域的普通技术人员有能力决定那些是他们所需最有益的技术。1.细胞膜结合试验:[35S]GTPγS试验
当G蛋白偶联受体处于活性状态,这或者是其与配体结合的结果或者作为其组成型活化的结果,该受体与G蛋白偶联并刺激GDP的释放和其后GTP与G蛋白的结合。G蛋白-受体复合物的α亚基作为GTP酶并慢慢地水解GTP为GDP,在此点受体通常发生失活。组成型活化受体继续把GDP转化为GTP。不可水解的GTP类似物[35S]GTPγS,可被用来展示[35S]GTPγS与表达组成型活化受体的膜的增强的结合。应用[35S]GTPγS结合测定组成型活化的优点是:(a)它对所有G蛋白偶联受体是普遍适用的;(b)它邻近细胞膜表面,在此处较少可能拣到影响细胞内级联反应的分子。
此试验利用G蛋白偶联受体刺激[35S]GTPγS,使其与表达相关受体的细胞膜结合的能力。因此本测定可用于直接识别法去筛选针对已知并且是组成型活化的G蛋白偶联受体的候选化合物。本测定是通用的,并可用于针对所有G蛋白偶联受体的药物发现。
[35S]GTPγS试验:在20mM HEPES、1至大约20mM的MgCl2(尽管20mM是优选的,但这个剂量可针对结果的最优化进行调整)、pH7.4、与0.3和1.2nM之间的[35S]GTPγS(尽管1.2是优选的,但这个剂量可针对结果的最优进行调整)、以及12.5到75μg膜蛋白(例如,表达该受体的COS-7细胞;尽管75μg是优选的,本剂量可为最优化进行调整)和1μM GDP(这个剂量可针对结果的最优化进行改造)结合的缓冲液中温育一小时。接着加入麦胚凝集素小珠(25μl,Amersham),混合物在室温下再温育30分钟,然后试管在1500×g、室温下离心5分钟,并在闪烁计数器上记数。
已发现了一种花费较低但同样适用的替代方法,其也满足大规模筛选的需要。Flash PlateTM和WallacTM scintistrips可用来构成一种高流通量的[35S]GTPγS结合实验。此外,利用这一技术,该实验可用于已知GPCR在监测[35S]GTPγS结合效率的同时,检测含氚配体与该受体的结合。这可能因为Wallac beta计数器可转换能量窗以观察氚和35S-标记的探针。该试验也可用于检测其他类型的源于受体活化的膜活化事件。例如,该分析可用于监测多种受体(包括蛋白偶联的和酪氨酸激酶受体)的32P磷酸化。当膜离心于孔底,该结合的[35S]GTPγS或32P磷酸化的受体将活化覆盖于孔上的闪烁剂。Scintistrips(Wallac)被用于显示该原理。此外,该实验也可利用放射性标记的配体用于检测结合于受体上的配体。同样,当这种放射性标记结合的配体离心于孔底时,该闪烁标记临近放射性标记的配体,导致活化和检测。2.基于膜的cAMP
设计用来进行基于细胞测定的Flash PlateTM腺苷酸环化酶试剂盒(New England Nuclear;目录号SMP004A)被改进以应用于未加工的胞浆膜。闪烁板的孔含有闪烁剂包被层,其中含有识别cAMP的特异抗体。在孔中产生的cAMP通过直接和放射性cAMP示踪物竞争与cAMP抗体结合而被定量。下面是测量在表达受体的膜上cAMP水平变化的主要程序。
在转染后大约3天收集转染的细胞。通过将含20mM HEPES,pH7.4和10mM MgCl2的缓冲液中悬浮的细胞均质化,制备膜。均质化是使用Brinkman PolytronTM在冰上进行约10秒钟。产生的匀浆在4℃,49000×g离心15分钟。然后将所产生的沉淀悬浮于包含20mMHEPES,pH7.4和0.1mM EDTA的缓冲液中,匀浆10秒,然后在4℃,49000×g离心15分钟。所产生的粒状沉淀在使用前储存于-80℃。检测当天,该膜的沉淀在室温下缓慢融化,重新悬浮于包含20mM HEPES,Ph7.4和10mM MgCl2(尽管优选此处列出的值,其仍可最佳化)的缓冲液中,使蛋白终浓度为0.60mg/ml(重新悬浮的膜放置于冰上备用)。
按照制造商的指示制备和维持cAMP标准品和检测缓冲液(含有加入到11ml检测缓冲液的2μCi示踪物[125I cAMP(100μl)])。为筛选用的分析缓冲液被新鲜制备,它包含20mM HEPES,pH7.4,10mMMgCl2,20mM(Sigma),0.1单位/ml肌酸磷酸激酶,50μl GTP(Sigma)和0.2mM ATP(Sigma);分析用缓冲液可在冰上贮存备用。该试验是首先加入50μl试验缓冲液,接着在NEN Flash平板上加入50μl膜悬浮液。所产生的实验混合物在室温培养60分钟,然后加入100μl检测缓冲液。培养板接着再温育2-4小时,然后用Wallac MicroBetaTM闪烁计数器记数。cAMP/孔的数值从标准cAMP曲线外推,该曲线包括在每个测定板之内。3.Gi偶联靶GPCRs的基于细胞的cAMP
TSHR是一种Gs偶联的GPCR,当活化时引起cAMP的累积。将氨基酸残基623突变(即,将丙氨酸残基变为异亮氨酸残基)可使TSHR组成型活化。其核酸序列参见SEQ ID NO:402,其氨基酸序列参见SEQ ID NO:403。预期Gi偶联受体抑制腺苷酸环化酶,并因此降低cAMP的水平,从而使cAMP水平的评估有难度。检测作为组成型活化Gi偶联受体指示的cAMP产量的降低,一种有效手段是通过共转染来实现的,最优选的,是通过以非内源的组成型活化TSHR(TSHR-A623I)(或一个内源组成型活化的Gs偶联受体)为“信号增强子”,和Gi偶联的靶GPCR共转染,确定cAMP的基准水平。在产生非内源性Gi偶联受体后,此非内源的靶GPCR与信号增强子共转染,并用做筛选的材料。在使用cAMP分析时,我们将利用这一方法有效地产生信号;该方法优选地用于针对Gi偶联受体的侯选化合物的直接识别。要注意的是,对于Gi偶联GPCR,使用该方法时,该靶GPCR的反激动剂会增加cAMP信号,而激动剂会降低cAMP信号。
第一天,Hek-293和Hek-293T细胞以每孔2×104个细胞的密度植于板上。第二天,准备两支试管(比例是每板用于一支试管):通过混合2μg的转染到哺乳动物细胞的各受体DNA,总量为4μg的DNA(例如pCMV载体;带有突变THSR的pCMV载体(TSHR-A623I);TSHR-A623I和GPR24等)在1.2ml无血清的DMEM(Irvine Scientific,Irvine,CA)来制备试管A;通过在1.2ml无血清DMEM中混合120μllipofectamine(Gibco BRL)制备试管B。把试管A和B互倾混合(几次),然后在室温下温育30-45分钟。混合物被称为“转染混合物”。植入的Hep-293细胞用1XPBS洗涤,然后加入10ml无血清的DMEM。把2.4ml转染混合物加入到细胞中去,然后在37℃/5%CO2下温育4小时。接着通过抽吸移去转染混合物,然后加入25ml的DMEM/10%胎牛血清。接着细胞在37℃/5%CO2温育。24小时后收获细胞并用来进行分析。
设计用来进行基于细胞的试验的Flash PlateTM腺苷酸环化酶试剂盒(New England Nuclear;目录号SMP004A),经过改进以应用于未加工的胞浆膜。闪烁板的孔含有闪烁剂包被层,其中含有识别cAMP的特异抗体。在孔中产生的cAMP通过放射性cAMP示踪物与cAMP抗体的直接竞争的结合而被定量。下面是测量在表达受体的全细胞中cAMP水平变化程序的主要程序。
在瞬时转染后大约24小时收获转染的细胞,小心抽吸培养液并弃去。向其中轻缓加入10ml PBS,接着小心地抽吸。每板加入1ml Sigma细胞分散缓冲液和3ml PBS。吸出细胞,将收获的细胞悬液加入50毫升的锥型离心管,然后在室温于1100rpm离心5分钟。以适当量的PBS小心地重悬细胞沉淀(每板约3ml)。用血细胞计数器计数,并用PBS调整到适当的细胞数量(最终的浓度约为每孔50μl)。
按照制造商的指示制备和维持cAMP标准品和检测缓冲液(含有1μCi示踪物[125I cAMP(50μl)]的11ml检测缓冲液)。为筛选用的分析缓冲液被新鲜制备,它含有50μl刺激缓冲液,3μl的实验化合物(终试验浓度为12μM)和50μl的细胞;试验缓冲液可在冰上贮存备用。该试验首先在合适的孔中加入50μl cAMP标准,接着加入50μl PBSA到孔H-11和H-12。在所有的孔内加入50μl刺激缓冲液。使用可分散3μl化合物溶液的针具将选定的化合物(如TSH,10nM MCH,MCH/TSH)加入适当的孔中,实验化合物的终浓度为12μM,实验总体积为100μl。然后将细胞加入孔中,室温培养60分钟,然后在每孔中加入100μl含示踪cAMP的检测缓冲液(Detection Mix)。培养板接着再温育2小时,然后用Wallac MicroBetaTM闪烁计数器记数。将cAMP/孔的数值从标准cAMP曲线外推,该曲线包括在每个测定板之内。
图1表明用TSHR-A623I(存在TSH)和非内源性组成型活化的GPR24(“24-IC3-SST2”)共转染的细胞中cAMP的产量(每孔262.266pmol cAMP),比TSHR-A623I和内源性GPR24(“GPR24 wt”)共转染的细胞中cAMP的产量(每孔336.50293pmol cAMP)降低22%。TSHR-A623I与非内源性组成型活化的GPR24(“I261Q”)的共转染与“GPR24wt”相比,在cAMP的产量上有27%的降低。这种cAMP产量的降低表明非内源性的GPR24(“I261Q”)是组成型活化的。因此,通过增加cAMP信号而影响GPR24受体的侯选化合物是反激动剂,而GPR24的激动剂将降低cAMP信号。基于图1所示数据,当用于TSHR(利用cAMP实验的组成型活化的共转染方法)时,24-IC3-SST2和I261Q是最优选的GPR24的非内源形式。
图2表明用TSHR-A623I(存在TSH)和非内源性组成型活化的GPR5(“V224K”)共转染的细胞中cAMP的产量(每孔23.5pmolcAMP),比TSHR-A623I和内源性GPR5(“GPR5wt”)共转染的cAMP的产量(每孔58.79pmol cAMP)降低60%。TSHR-A623I和“V225K”的共转染与TSHR-A623I和“GPR5wt”的共转染分别比pCMV和TSHR-A623I的共转染(每孔106.75pmol cAMP)在cAMP的产量上有78%和45%的降低。如上所述,cAMP产量的降低表明组成型活化的GPR5。因此,优选的侯选化合物(即,反激动剂)将可能结合Gi偶联的受体以增加活化信号。
优选,并且也在前述指明的,为了确定小分子侯选化合物是否靶向Gi偶联的靶受体,如TSHR-A623I,这种直接识别的侯选化合物优选在该靶受体不存在的条件下针对信号增强子进行筛选。C.基于报告基因的测定1.CRE-Luc报告基因测定(Gs相关的受体)
检测Gs刺激的一个方法是基于转录因子CREB的已知特性,该CREB以cAMP依赖的方式被活化。使用PathDetectTM CREB反报道基因(trans-Reporting)系统(Stratagene,分类号219010),按商家说明分析293或293T细胞内Gs偶联的活性。用上述系统中的质粒组分和用哺乳动物转染试剂盒(Stratagene,分类号200285)中编码内源或突变受体的指定的表达质粒按商家说明转染细胞。简而言之:每个试剂盒将400ng pFR-Luc(包含Gal4识别序列的荧光素酶报道基因质粒),40ng pFA2-CREB(包含Gal4 DNA-结合结构域的Gal4-CREB融合蛋白),80ng pCMV-受体表达质粒(包含受体)和20ng CMV-SEAP(分泌型碱性磷酸酶表达质粒;检测碱性磷酸酶在转染细胞介质中的活性,以控制不同样品之间转染效率的差异)组合于磷酸钙沉淀中。将沉淀的一半等分于96孔平板中的3个孔内,保持细胞过夜,第二天早晨用新鲜培养基替换。转染48小时后,对细胞进行处理和试验,如对于荧光素酶活性的试验。2、8XCRE-Luc报道基因试验
HEK-293T细胞以每孔3×104个细胞的密度植于96孔板上,第二天按商家说明用脂质转染胺(Lipofectamine)试剂(BRL)进行转染。每6孔转染制备DNA/脂质混合物如下:100μl DMEM中的260ng质粒DNA温和地与100μl DMEM中的2μl脂质混和(260ng以下组成质粒DNA:200ng 8×CRE-Luc报道基因质粒(参见以下及图1关于该质粒部分的图示),50ng包含内源受体或非内源受体的pCMV,或单独的pCMV,以及10ng GPRS表达质粒(GPRS在pcDNA3(Invitrogen)中))。8XCRE-Luc报道基因质粒的制备如下:在pβgal基本载体(Clontech)的BglV-HindIII位点克隆大鼠促生长抑制素的启动子(-71/+51)获得的SRIF-β-gal载体,8拷贝的cAMP效应元件通过PCR由腺病毒模板AdpCF126CCRE8获得(参见,7人基因疗法(Human Gene Therapy)1883(1996)),将之克隆到SRIF-β-gal载体的Kpn-BglV位点中,产生8XCRE-β-gal报告载体。用荧光素酶基因取代8XCRE-β-gal报告载体中的β-半乳糖苷酶基因,产生8XCRE-Lus报告质粒,所述荧光素酶基因由pGL-3基本载体(Promega)的HindIII-BamHI位点获得。室温下放置30分钟后,DNA/脂质混合物用400μl DMEM稀释,每孔加入100μl稀释的混合物,在细胞培养箱中培养4小时后每孔中加入100μl含10%FCS的DMEM,第二天转染的细胞每孔换成200μl含10%FCS的DMEM,8小时后,用PBS清洗一次,各样品孔改为100μl不含酚红的DMEM。次日用LucLiteTM报告基因分析试剂盒(Packard),按商家说明和在1450 MicroBetaTM闪烁发光计数器(Wallac)上读数测定荧光素酶活性。
图3A表示非内源性组成型活化的人多巴胺D1受体的活性(189270相对光单位)与内源性多巴胺D1受体的活性(70622相对光单位)相比有63%的增加。
图3B表示相对于其各自的内源性GPCR变体,非内源性组成型活化的人OPRM(一种Gi偶联的受体,参见实施例4(3))变体的活性有43%的降低,非内源性组成型活化的人5-HT1A(一种Gi偶联的受体,参见实施例4(3))的活性有53%的降低,非内源性组成型活化的人5-HT1B的活性有91%的增加,以及非内源性组成型活化的人5-HT2B的活性有20%的增加。
图3C表示相对于其各自的内源性GPCR变体,非内源性组成型活化的人CCR3的活性有29%的增加,非内源性组成型活化的人NTSR1变体的活性有41%的增加,非内源性组成型活化的人CB2变体的活性有51%的增加,以及非内源性组成型活化的人CXCR4变体(一种Gi偶联的受体,参见实施例4(3))的活性有40%的降低。
图3D表示相对于其各自的内源性GPCR,非内源性组成型活化的人PTHR1变体的活性有75%的增加,非内源性组成型活化的人PTHR2变体的活性有74%的增加,非内源性组成型活化的人SCTR变体的活性有56%的增加,非内源性组成型活化的人PACAP变体的活性有96%的增加,非内源性组成型活化的人VIPR1变体的活性有88%的增加,以及非内源性组成型活化的人VIPR2变体的活性有91%的增加。
图3E表示相对于其各自的内源性GPCR,非内源性组成型活化的人NTSR1变体的活性有51%的增加,非内源性组成型活化的人M1变体的活性有31%的降低,非内源性组成型活化的人M2变体的活性有19%的降低,非内源性组成型活化的人M3变体的活性有32%的增加,非内源性组成型活化的人M4变体的活性有33%的降低,非内源性组成型活化的人M5变体的活性有17%的降低,以及非内源性组成型活化的人5-HT1D变体的活性有60%的增加。并指明M2、M4和5-HT1D是Gi偶联的,NTSR1、M1、M3和M5是Gq偶联的。3.AP1报告基因试验(Gq偶联的受体)
测定Gq刺激依赖的方法依赖于Gq依赖的磷脂酶C已知的特性,即它可引起在其启动子中含AP1元件的基因活化。按照上述CREB报告基因测定所说的程序,使用PathdetectTM AP-1 cis-Reporting System(Stratagene,Catalogue#219073),其中只是将磷酸钙沉淀的组分改为410ng pAP1-Luc、80ng pCMV-受体表达质粒和20ng CMV-SEAP。4.SRF-Luc报告基因试验(Gq偶联受体)
检测Gq刺激的一个方法凭借Gq依赖性磷脂酶C的已知特性,其引起启动子中含血清应答因子的基因活化。PathdetectTM SRF-Luc报告系统(Stratagene)可用来分析Gq偶联的活性,比如在COS7细胞中的活性。应用Mammalian TransfectionTM试剂盒(Stratagene,Catalogue#200285),用该系统中各种质粒组分及标明的编码内源或非内源GPCR的表达质粒,按商家说明转染细胞。简单地讲,410ng SRF-Luc、80ngpCMV受体表达质粒和20ng CMV-SEAP(分泌碱性磷酸酶的表达质粒;测定转染细胞培养基中碱性磷酸酶活性以控制样品间转染效率的差别),依各个商家的说明与磷酸钙沉淀组合。一半的沉淀物等量地分配到96孔板的3个孔中,使细胞在无血清培养基中保持24小时。按说明书要求,在最后5个小时细胞与1μM血管紧张素一起培养,然后溶解细胞,使用LucLiteTM试剂盒(Packard,cat#6016911)和“Trilax1450 Microbeta”液体闪烁发光计数器(Wallac),按各个商家的说明分析荧光素酶活性,数据用GraphPad PrismTM 2.0a软件分析(GraphPadSoftware Inc.)。5.胞内IP3积累试验(Gq相关受体)
在第一天,含有该受体(内源的和/或非内源的)的细胞被接种于24孔培养板上,一般是1×105细胞/孔(虽然该数还可最佳化)。在第二天转染细胞,首先混合在50μl/孔无血清DMEM中的0.25μg DNA和在50μl/孔无血清DMEM中的2μl脂质转染胺。轻轻地混合溶液并在室温下温育15-30分钟。用0.5ml PBS洗涤细胞,把400μl无血清培养基与转染培养基混合并加到细胞中。然后在37℃/5%CO2下温育细胞3-4小时,再移去转染培养基,替换为1mL/孔常规培养基。在第三天,用3H-肌醇标记细胞。简短地说,移去培养基,细胞用0.5ml PBS洗涤,接着加入0.5ml/孔无肌醇/无血清培养基(GIBCO BRL)和0.25μCi3H-肌醇/孔,在37℃/5%CO2下温育细胞16-18小时。在第四天,用0.5mlPBS洗涤细胞,加入0.45ml试验培养基,其中含有无肌醇/无血清培养基10μM巴吉林10mM氯化锂或0.4ml试验培养基和50μl 10×ketaserin(ket),以得到10μM的终浓度。然后在37℃温育细胞30分钟。用0.5ml PBS洗涤细胞,加入200μl/孔新鲜的/冰冷的终止液(1MKOH、18mM硼酸钠、3.8mM EDTA)。该溶液在冰上放置5-10分钟或直到细胞被溶解,然后用200μl新鲜的/冰冷的中和液(7.5%HCl)中和。然后把溶解物转移到1.5ml离心管中,每管加入1ml/氯仿/甲醇(1∶2)。然后使溶液涡旋15秒钟,把上层相加至Biorad AG1-X8TM阴离子交换树脂(100-200目)。首先,树脂以1∶1.25W/V的比例用水洗涤,向柱中加载0.9ml的上层相溶液。用10mL 5mM肌醇和10ml 5mM的硼酸钠/60mM甲酸钠洗涤柱子。肌醇三磷酸酯被洗提入闪烁管中,其中含有10ml闪烁混合液,它有2ml 0.1M甲酸/1M甲酸铵。通过用10ml 0.1M甲酸/3M甲酸铵洗涤和用H2O洗涤两次来再生交换柱,柱子贮存在4℃的水中。
图4代表了IP3实验中的两个优选的非内源性组成型活化的实例GPR24,24-IC3-SST2和I261Q的变体。当与内源形式的GPR24(“GPR24wt”)相比,24-IC3-SST2表现IP3积累的27%的增加,而I261Q表现约32%的增加。实施例6GPCR融合蛋白的制备
组成型活化的GPCR-G蛋白融合构建体的设计如下完成:建造大鼠G蛋白Gsα(长式;ltoch,H.等,83 PNAS 3776(1986))的5′和3′端,使之包括HindIII(5′-AAGCTT-3′)序列。正确的序列(包括HindIII的侧翼序列)确认之后,通过利用该载体的HindIII限制性位点进行亚克隆,将所述完整的序列插入pcDNA3.1(-)(Invitrogen,cat.no.V795-20)。亚克隆进入pcDNA3.1(-)之后,确认Gsα序列的正确方向,然后证实在HindIII序列上带有大鼠Gsα基因的该经修饰的pcDNA3.1(-),该载体现在可用作“通用的”Gsα蛋白载体。pcDNA3.1(-)载在HindIII位点的上游含有多种已知的限制性位点,这样能够有利地提供在Gs蛋白上游插入内源组成型活化GPCR的编码序列的能力。可以应用同样的方法创造其他“通用的”G蛋白载体,当然,可以应用其他可买到的或本领域技术人员已知的专用载体----重要的标准是GPCR序列处于G蛋白序列的上游并与G蛋白序列符合读框。1、TSHR-Gsα融合蛋白a、制备TSHR的稳定的细胞系
约1.2到1.3×107 HEK-293细胞铺板于15cm组织培养平板。在包含10%胎牛血清和1%丙酮酸钠,L-谷氨酰胺和抗生素的DME高葡萄糖培养基中生长。铺板后24小时293细胞达到约80%的汇合度时,细胞用12μg DNA转染。该12μg DNA与60μl的脂质转染胺和2mL无血清的DME高葡萄糖培养基组合。从平板中吸去培养基,用无血清的培养基洗涤平板一次。将该DNA,脂质转染胺以及培养基的混合物与10mL无血清培养基一同加入平板。37℃培养4-5小时后,吸去该培养基,加入25mL含血清的培养基。转染24小时后,再一次吸去培养基,加入新鲜的含血清培养基。转染48小时后,吸去培养基,加入包含终浓度为500μg/mL的遗传霉素(G418药物)的含血清培养基。所述转染细胞用含G418抗性基因的阳性转染细胞进行选择。随着选择的发生,每4-5天换一次培养基。在选择中,细胞生长到稳定状态,或分裂以便进行稳定的克隆选择。b、TSHR(A623K)融合蛋白
TSHR-Gsα融合蛋白构建体如下制备:为内源性组成型活化和非内源性组成型活化的TSHR设计的引物如下:
5′-gatc[TCTAGA]ATGAGGCCGGCGGACTTGCTGC-3′-(SEQ.ID.NO.:582;有义)
5′-gcta[GATATC]CGCAAAACCGTTTGCATATACTC-3′-(SEQ.ID.NO.:583,反义)
小写的核苷酸作为间隔子包含在内源TSHR和G蛋白之间的限制性位点前。有义和反义引物分别包含了XbaI和EcorV限制性位点。
然后应用PCR得到各个受体序列,用于上面公开的Gsα通用载体融合,各使用以下程序:100ng用于TSHR(A623K)的cDNA加到不同的管中,其中各管含有每个引物(有义和反义)2μl,3μl 10mMdNTPs,10μl 10×TaqPlusTM精确缓冲液,1μl TaqPlusTM精确聚合酶(Stratagene:#600211),及80μl水。用于TSHR的反应温度和循环时间如下:初始变性步骤在94℃下进行5分钟,然后进行一个94℃30秒;55℃30秒;72℃2分钟的循环。最后的延伸时间是72℃下进行10分钟。PCR产物走1%琼脂糖凝胶,然后纯化(数据未显示)。纯化产物用XbaI和EcorV(New England Biolabs)消化,所需的插入片段经分离纯化,连接到Gs通用载体的各个限制性位点。转化后分离阳性克隆并用限制性酶酶切确认;用Hek-293细胞按下述程序实现表达。对TSHR:Gs融合蛋白的每个阳性克隆进行测序并使其可用于直接鉴别候选化合物。(核苷酸序列见SEQ.ID.NO.:588,氨基酸序列见SEQ.ID.NO.:589)。
TSHR(A623K)的非内源形式定位于大鼠G蛋白Gsα的上游(即从第1位到第2292位核苷酸;参见SEQ.ID.NO.:586,氨基酸残基是从第1位到第764位;参见SEQ.ID.NO.:587)。TSHR(A623K)可直接连接于G蛋白上,或者其可通过二者间的间隔残基相连。对于TSHR,在非内源性GPCR和G蛋白Gsα的起始密码子之间有24个氨基酸残基(等于72个核苷酸)。因此,该Gs蛋白位于核苷酸第2365位到3549位之间(参见SEQ.ID.NO.:586),和位于氨基酸残基第789位到第1183位之间(参见SEQ.ID.NO.:587)。本领域熟练技术人员有能力选择构建GPCR融合蛋白的技术,其中G蛋白融合于目的GPCR的3’末端。
用实施例4(2)中所述方法,分析(稳定GPCR并筛选侯选化合物,如实施例6所述)并证实了GPCR融合蛋白的组成型活化。图5中证实了TSHR(A623K)-Gαs融合蛋白与对照载体(pCMV)相比cAMP有87%的增加。2、GPR24-Giα融合蛋白
GPR24-Giα融合蛋白构建体如下制备:为内源性组成型活化和非内源性组成型活化的GPR24设计的引物如下:
5′-GTGAAGCTTGCCCGGGCAGGATGGACCTGG-3′(SEQ.ID.NO.:584;有义)5′-ATCTAGAGGTGCCTTTGCTTTCTG-3′-(SEQ.ID.NO.:585,反义)。有义和反义引物分别包含了KB4和XbaI限制性位点。
然后应用PCR得到用于与上面公开的Giα通用载体中的融合的各个受体序列,各PCR使用以下程序:100ng用于GPR24的cDNA加到不同的管中,其中各管含有每个引物(有义和反义)2μl,3μl 10mMdNTPs,10μl 10×TaqPlusTM精确缓冲液,1μl TaqPlusTM精确聚合酶(Stratagene:#600211),及80μl水。用于GPR24的反应温度和循环时间如下:初始变性步骤在94℃下进行5分钟,然后进行94℃30秒;55℃30秒;72℃2分钟的循环。最后的延伸时间是72℃下进行10分钟。PCR产物走1%琼脂糖凝胶,然后纯化(数据未显示),纯化产物用KB4和XbaI(New England Biolabs)消化,所需的插入片段经分离纯化连接到Gi通用载体中的各个限制性位点。转化后分离阳性克隆并用限制性酶酶切确认;用Hek-293细胞按下述程序实现表达。对GPR24:Gi一融合蛋白的每个阳性克隆进行测序并用于直接鉴别候选化合物。(核苷酸序列见SEQ.ID.NO.:590,氨基酸序列见SEQ.ID.NO.:591)。
GPR24的非内源形式定位于G蛋白Gi的上游,即从第1位核苷酸到第1059位(参见SEQ.ID.NO.:588),氨基酸残基是从第1位到第353位(参见SEQ.ID.NO.:589)。对于GPR24,在内源性(或非内源性)GPCR和G蛋白Giα的起始密码子之间有2个氨基酸残基(等于6个核苷酸)。因此,该Gi蛋白位于核苷酸第1066位到2133位之间(参见SEQ.ID.NO.:588),和位于氨基酸残基第356位到第711位之间(参见SEQ.ID.NO.:589)。本领域熟练技术人员有能力选择构建GPCR融合蛋白的技术,其中G蛋白融合于目的GPCR的3’末端。
尽管以上说明Gi偶联的受体(如GPR24)可与共转染的方法联合使用,其是在基于cAMP实验背景,并基于Gi对于cAMP水平的影响而预测的。但对于其他类型的实验,如基于GTP的实验,这种共转染的方法不是必须的。因此,对于如基于GTP实验之类的实验,优选GPCR融合蛋白方法,对于基于GTP的GPR24实验,优选GPR24:Gi融合蛋白。实施例6方案:用[35S]GTPγS直接识别反激动剂和激动剂
尽管内源性GPCRs可用于直接筛选作为,如反激动剂的侯选化合物,由于一些仍未知的原因,实验内的差异可能变的很大。因此,优选用非内源性组成型活化的GPCR用于上述GPCR融合蛋白。我们可以确定在使用这种蛋白时,实验内的差异显著地稳定并且其中获得了有效的信噪比。这种有利的结果使能够更有效地识别侯选化合物。因此,优选在直接识别中使用GPCR融合蛋白,并且使用时利用以下实验方案。1.膜制备
包含目的非内源性组成型活化的GPCR融合蛋白的膜和用于直接识别作为反激动剂、激动剂或部分激动剂的候选化合物的膜,优选按如下步骤制备:a.材料
“膜提取缓冲液”由20mM HEPES和10mM EDTA(pH7.4)组成;“膜清洗缓冲液”由20mM HEPES和0.1mM EDTA组成,pH7.4;“结合缓冲液”由20mM HEPES、100mM NaCl及10mM MgCl2组成,pH7.4。b.步骤
整个过程中所有材料均置于冰上。首先,将培养基从汇合的单层细胞中吸去,随后用10ml冷的PBS清洗,随后吸掉,这之后将5ml膜提取缓冲液加到提取细胞上,随后将细胞提取物转移到50ml离心管中(4℃下20,000rpm离心17分钟),这之后吸出上清液,将沉淀重悬于30ml膜清洗缓冲液,随后4℃下20,000rpm离心17分钟,然后吸出上清液,沉淀重悬于结合缓冲液中,然后用Brinkman polytronTM均化器进行均化(15-20秒剧烈振动直到所有材料处悬浮状态),此处称之为“膜蛋白”。2.Bradford蛋白分析
均化以后,这些膜的蛋白浓度用Bradford蛋白试验测定(蛋白可以稀释成大约1.5mg/ml,等份分装和冷冻(-80℃)备用;冷冻状态下,所用规程如下:分析的当天,将冷冻的膜蛋白室温下溶化,随后用polytron以大约12×1000rpm涡旋振荡均化5~10秒;请注意,对于多次制备,不同制备物的均化之间应该彻底洗净均化器)。a.材料
结合缓冲液(如上);Bradford染色试剂,Bradford蛋白标准物,按商家说明使用(Biorad,cat.no.500-0006)。b.步骤
准备两个试管,一个含有膜,一个作为“空白”对照。每管装入800μl结合缓冲液,之后将10μl Bradford蛋白标准物(1mg/ml)加到每个试管中,然后10μl膜蛋白只加到一个试管中(空白管中不加),这之后将200μl Bradford染色试剂加到每个试管中,随后每个试管经涡旋振荡。5分钟后,试管再次涡旋振荡,将其中的材料转移到比色杯中,然后比色杯用CECIL 3041分光光度计在595波长下读数。3.直接识别试验a.材料
GDP缓冲液由37.5ml结合缓冲液和2mg GDP(Sigma,cat.no.G.7127)组成,随后用结合缓冲液作一系列稀释以得到0.2μM GDP(每孔中GDP的终浓度为0.1μM GDP);每孔中含有候选化合物,终体积为200μl,其中有100μl GDP缓冲液(终浓度0.1μM GDP),50μl悬浮于结合缓冲液中的膜蛋白,及50μl溶于结合缓冲液中的[35S]GTPγS(0.6nM)(每10ml结合缓冲液2.5μl[35S]GTPγS)。b.步骤
候选化合物优选用96-孔板筛选(可以在-80℃冷冻)。将膜蛋白(或带有除了GPCR融合蛋白的表达载体的膜,作为对照)简单地均化至悬浮状态,然后用上述的Bradford蛋白试验确定蛋白浓度。然后膜蛋白(和对照)用结合缓冲液稀释成0.25mg/ml(最终试验浓度,12.5μg/孔),这之后,100μl GDP缓冲液加到Wallac ScintistripTM(Wallac)的每个样品孔中。然后用5μl针具将5μl候选化合物转移到这些样品孔中(即5μl在200μl总分析体积中为1∶40比例,因而候选化合物最终的筛选浓度为10μM)。再有,为避免污染,每次转移步骤后,针具应在包括水(1X),乙醇(1X)和水(2X)的储液器中清洗三次,----将多余液体在每次清洗后从针具上甩掉,用纸和纸巾干燥。这之后50μl膜蛋白加到每个样品孔中(对照样品孔含有不带GPCR融合蛋白的膜),室温下预温育5-10分钟。这之后,50μl结合缓冲液中的[35S]GTPγS(0.6nM)加到每个样品孔中,随后室温下于摇床上温育60分钟(再有,本实施例中,培养板用金属箔盖住)。然后将板以4000RPM 22℃下旋转15分钟终止试验,然后用8道支管吸净板,用板盖盖住,最后板用设置在“Prot.#37”档(依各商家说明)的Wallac 1450读数。实施例7方案:确认实验
如上所述用独立实验方法以提供对直接识别的侯选化合物的确认,然后优选利用一种确认方法。在这种情况下,该优选的确认方法是基于环化酶的试验。
优选应用经改进的Flash PlateTM腺苷酸环化酶试剂盒(NewEngland;Cat.no.SMP004A),按下面的规程证实直接识别的候选化合物作为非内源性组成型活化的GPCR的反激动剂和激动剂。
转染后大约三天收集转染细胞。在含有20mM HEPES(pH7.4)和l0mM MgCl2的缓冲液中,通过将悬浮的细胞均化来制备膜。用Brinkman PolytronTM在冰上进行均化大约10秒,产生的匀浆4℃下49,000×g离心15分钟,然后产生的沉淀重悬于含有20mM HEPES(pH7.4)和0.1mM EDTA的缓冲液中,均化10秒,随后4℃下49,000×g离心15分钟,产生的沉淀在-80℃保存备用。直接识别筛选当天,将膜沉淀于室温下缓慢融化,并重悬于含有20mM HEPES(pH7.4)和10mM MgCl2的缓冲液中,产生0.6mg/ml的最终蛋白浓度(重悬的膜置于冰上备用)。
cAMP标准物和测定缓冲液(2μCi示踪物[125I cAMP(100μl)]加到11ml测定缓冲液中),根据商家说明制备并保管。制备新鲜的试验缓冲液用于筛选,其中包含20mM HEPES(pH7.4),10mM MgCl2,20mM磷酸肌酸(Sigma),0.1单位/ml肌酸磷酸激酶(Sigma),50μM GTP(Sigma),及0.2mM ATP(Sigma);试验缓冲液可在冰上保存备用。
优选将以上识别的候选化合物(如冷冻,室温下融化)加到96孔板的样品孔中(3μl/孔,12μM的试验终浓度),与40μl膜蛋白(30μg/孔)和50μl试验缓冲液合在一起。然后将该混合物在室温下温育30分钟,同时轻轻摇动。
温育完成后,100μl测定缓冲液加到每个样品孔中,随后温育2~24小时,然后板在Wallac MicroBetaTM读板器中用“Prot.#31”档计数(依各商家说明操作)。实施例8基于配体的确认实验
由转染的Hek-293细胞(参见实施例3),通过在20mM HEPES和10mM EDTA(pH7.4)中均化,然后49,000×g离心15分钟来制备膜。将沉淀重新悬浮于20mM HEPES和0.1mM EDTA(pH7.4)中,用Polytron匀浆器(Brinkman)以5000rpm均化10秒,49,000×g离心15分钟。最终产生的沉淀重新悬浮于20mM HEPES和10mM EDTA(pH7.4)中,用Polytron匀浆器(Brinkman)以5000rpm均化10秒。
基于配体的确认实验在96孔板中以200μl体积的三份进行重复试验。使用试验缓冲液(20mM HEPES和10mM MgCl2,pH7.4)稀释膜,氚化的反激动剂和/或激动剂以及该受体的内源性配体(用于定义非特异性结合)。最终的实验浓度将包含1nM氚化的反激动剂和/或激动剂,50μg膜蛋白(包含受体)和100μm内源性配体。激动剂实验在37℃孵育1小时,而反激动剂实验在室温孵育1小时。使用Skatron细胞收集器,用冰冷的结合缓冲液快速滤过Wallac Filtermat Type B而终止实验。用Wallac 1205 BetaPlate计数器测定其放射活性。
此方法仅用来理解直接识别的侯选化合物对于配体结合的影响。如本领域技术人员所能理解的,这些直接识别的侯选化合物可能是别构调节物(即,影响受体的功能活性但不抑制内源配体与该受体结合的化合物)。别构调节剂包括反激动剂,部分激动剂和激动剂。
本专利申请文件中提到的每个专利文件,包括未决的和相关的专利申请,除非有特别说明,均以其全文引入本申请作参考。本领域的专业技术人员所能想到的本发明的修改和扩展均在以上公开以及以下的权利要求范围之内。
虽然本领域的普通技术人员可以得到许多不同的载体为内源和非内源性已知GPCRs的目的使用,但优选用pCMV载体。按照国际承认用于专利程序的微生物保存布达佩斯条约,该载体于1998年10月13日保存在美国典型培养物保藏中心(American Type CultureCollection)(ATCC)(University Blvd,Manassas,VA20110-2209USA)。其DNA经ATCC测定并得到确认。ATCC为pCMV给出了下列保藏号ATCC#203351。
序列表<110>阿瑞那制药公司(Arena Pharmaceuticals,Inc.)<120>非内源性组成型活化的已知G蛋白偶联受体(Non-Endogenous,ConstitutivelyActivated G Protein-Coupled Receptors)<130>AREN0394<150>60/195,747<151>2000-04-07<150>PCT/US01/11098<151>2001-04-05<160>589<170>PatentIn version 3.1<210>1<211>36<212>DNA<213>智人(Homo sapiens)<400>1cggaagctta gccatggatg tgctcagccc tggtca 36<210>2<211>34<212>DNA<213>智人(Homo sapiens)<400>2ccggaattcc tggcggcaga agttacactt aatg 34<210>3<211>32<212>DNA<213>智人(Homo sapiens)<400>3tccaagcttg gggcgaggag agccatggag ga 32<210>4<211>35<212>DNA<213>智人(Homo sapiens)<400>4ggcgaattca cttgtgcact taaaacgtat cagtt 35<210>5<211>30<212>DNA<213>智人(Homo sapiens)<400>5atctaccatg tccccactga accagtcagc 30<210>6<211>32<212>DNA<213>智人(Homo sapiens)<400>6atagaattcg gaggccttcc ggaaagggac aa 32<210>7<211>34<212>DNA<213>智人(Homo sapiens)<400>7ccacagtgtc gactgaaaca agggaaacat gaac 34<210>8<211>25<212>DNA<213>智人(Homo sapiens)<400>8cagtatgctc tcggcatcta atgag 25<210>9<211>31<212>DNA<213>智人(Homo sapiens)<400>9atcaccatgg atttcttaaa ttcatctgat c 31<210>10<211>33<212>DNA<213>智人(Homo sapiens)<400>10ttaggatcca catcgacatc gcacaagctt ttg 33<210>11<211>37<212>DNA<213>智人(Homo sapiens)<400>11gaaaagcttg ccatggctct ctcttacaga gtgtctg 37<210>12<211>35<212>DNA<213>智人(Homo sapiens)<400>12gttggatcct acataactaa cttgctcttc agttt 35<210>13<211>32<212>DNA<213>智人(Homo sapiens)<400>13atcaccatgg acaaacttga tgctaatgtg ag 32<210>14<211>33<212>DNA<213>智人(Homo sapiens)<400>14cctgaattcg aagcatgatt ccagggattc tgg 33<210>15<211>32<212>DNA<213>智人(Homo sapiens)<400>15atcaccatgg acaaacttga tgctaatgtg ag 32<210>16<211>33<212>DNA<213>智人(Homo sapiens)<400>16agggaattca gtgtcactgg gctgagcagc cac 33<210>17<211>32<212>DNA<213>智人(Homo sapiens)<400>17atcaccatgg acaaacttga tgctaatgtg ag 32<210>18<211>34<212>DNA<213>智人(Homo sapiens)<400>18ttggaattcg gatggtttgg tcaatcttct cttc 34<210>19<211>32<212>DNA<213>智人(Homo sapiens)<400>19atcaccatgg acaaacttga tgctaatgtg ag 32<210>20<211>39<212>DNA<213>智人(Homo sapiens)<400>20agggaattca aatcttagta catgtgtgga tccattaat 39<210>21<211>32<212>DNA<213>智人(Homo sapiens)<400>21atcaccatgg acaaacttga tgctaatgtg ag 32<210>22<211>33<212>DNA<213>智人(Homo sapiens)<400>22tcagaattcg acaggaactg gtctattgca gaa 33<210>23<211>39<212>DNA<213>智人(Homo sapiens)<400>23cctaagcttg ccatggattt accagtgaac ctaacctcc 39<210>24<211>35<212>DNA<213>智人(Homo sapiens)<400>24tctgaattcg tgttgcctag aaaagaagtt cttga 35<210>25<211>31<212>DNA<213>智人(Homo sapiens)<400>25agcggaattc ggcggcgcga tgatggacgt t 31<210>26<211>30<212>DNA<213>智人(Homo sapiens)<400>26tttcggatcc attgttctgc tttcaatcat 30<210>27<211>31<212>DNA<213>智人(Homo sapiens)<400>27caggaattca gaacacctgc cccagcccca c 31<210>28<211>33<212>DNA<213>智人(Homo sapiens)<400>28agcggatccc gatgaagtgt ccttggccag gga 33<210>29<211>30<212>DNA<213>智人(Homo sapiens)<400>29acagaattca gaagaaatgg ctcaaaggca 30<210>30<211>30<212>DNA<213>智人(Homo sapiens)<400>30catggatcct tgaaaagcta gaaactgtcc 30<210>31<211>33<212>DNA<213>智人(Homo sapiens)<400>31tgtaagcttc aggtcactgt gcatggcatc atc 33<210>32<211>36<212>DNA<213>智人(Homo sapiens)<400>32gctggatcca ttccgccaga aaagttggaa gatttc 36<210>33<211>34<212>DNA<213>智人(Homo sapiens)<400>33actaagcttc caaatgttct ctccctggaa gata 34<210>34<211>33<212>DNA<213>智人(Homo sapiens)<400>34gttgaattcc tgtctgctcc ctgcccagtc ctg 33<210>35<211>32<212>DNA<213>智人(Homo sapiens)<400>35cagaagctta gcaatggcgt ctttctctgc tg 32<210>36<211>37<212>DNA<213>智人(Homo sapiens)<400>36acaggatccc acagttgtac tatttctttc tgaaatg 37<210>37<211>34<212>DNA<213>智人(Homo sapiens)<400>37gggaagctta ggagaccaga acatgaactc cttc 34<210>38<211>33<212>DNA<213>智人(Homo sapiens)<400>38tgtgaattcc actgcctggg tcttctgggc cat 33<210>39<211>32<212>DNA<213>智人(Homo sapiens)<400>39gggaagcttt ctcagtcatt ttgagctcag cc 32<210>40<211>33<212>DNA<213>智人(Homo sapiens)<400>40tcagaattcc agagcctcgg cagacgtgtc tgt 33<210>41<211>33<212>DNA<213>智人(Homo sapiens)<400>41caaaagcttc tagacaagct cagtggaatc tga 33<210>42<211>34<212>DNA<213>智人(Homo sapiens)<400>42gccgaattcg caatcagaga ggtctagatc tctg 34<210>43<211>31<212>DNA<213>智人(Homo sapiens)<400>43gacaagcttc cccagtacat ccacaacatg c 31<210>44<211>33<212>DNA<213>智人(Homo sapiens)<400>44ctcggatcct aaaccagccg agacttcctg ctc 33<210>45<211>33<212>DNA<213>智人(Homo sapiens)<400>45atcgccatga caacctcact agatacagtt gag 33<210>46<211>33<212>DNA<213>智人(Homo sapiens)<400>46tctgaattca aacacaatag agagttccgg ctc 33<210>47<211>34<212>DNA<213>智人(Homo sapiens)<400>47gcaaagcttg gaacaagatg gattatcaag tgtc 34<210>48<211>33<212>DNA<213>智人(Homo sapiens)<400>48tccggatccc aagcccacag atatttcctg ctc 33<210>49<211>32<212>DNA<213>智人(Homo sapiens)<400>49tgaaagcttc ccgctgcctt gatggattat ac 32<210>50<211>34<212>DNA<213>智人(Homo sapiens)<400>50tgagaattcc aaaatgtagt ctacgctgga ggaa 34<210>51<211>59<212>DNA<213>智人(Homo sapiens)<400>51atcaccatga cacccacaga cttcacaagc cctattccta acatggctga tgactatgg 59<210>52<211>33<212>DNA<213>智人(Homo sapiens)<400>52gacgaattcg agggagagtg ctcctgaggt tgt 33<210>53<211>30<212>DNA<213>智人(Homo sapiens)<400>53atcaccatgg gagggcaccc gcagctccgt 30<210>54<211>33<212>DNA<213>智人(Homo sapiens)<400>54cgggaattcg actgctgtgg actgcttgat gct 33<210>55<211>54<212>DNA<213>智人(Homo sapiens)<400>55atcaccatgg aggggatcag tatatacact tcagataact acaccgagga aatg 54<210>56<211>35<212>DNA<213>智人(Homo sapiens)<400>56tctgaattcg ctggagtgaa aacttgaaga ctcag 35<210>57<211>30<212>DNA<213>智人(Homo sapiens)<400>57aagaagcttg gcatcacgca cctcctctgg 30<210>58<211>28<212>DNA<213>智人(Homo sapiens)<400>58ggctctagaa atgggtacaa agagtgtt 28<210>59<211>29<212>DNA<213>智人(Homo sapiens)<400>59cggaagcttc tggagcaggt agcagcatg 29<210>60<211>36<212>DNA<213>智人(Homo sapiens)<400>60cttggatcca gatgagctgt atttattact ggaacg 36<210>61<211>30<212>DNA<213>智人(Homo sapiens)<400>61atcaccatgg agacaaattc ctctctcccc 30<210>62<211>33<212>DNA<213>智人(Homo sapiens)<400>62cccgaattcc tttgcctgta actccacctc tgc 33<210>63<211>33<212>DNA<213>智人(Homo sapiens)<400>63gcaaagcttg ctgctggcaa gatggaaacc aac 33<210>64<211>33<212>DNA<213>智人(Homo sapiens)<400>64ccagaattcc attgcctgta actcagtctc tgc 33<210>65<211>30<212>DNA<213>智人(Homo sapiens)<400>65ccggaattcg ccgggacagc cccgcgggcc 30<210>66<211>33<212>DNA<213>智人(Homo sapiens)<400>66gcaggatcct tatcacacat gagtacaatt ggt 33<210>67<211>31<212>DNA<213>智人(Homo sapiens)<400>67ggcgaattcg gggtcagcgg caccatgaac g 31<210>68<211>29<212>DNA<213>智人(Homo sapiens)<400>68gtgggatccc agcgcgcccg ctaagtgct 29<210>69<211>30<212>DNA<213>智人(Homo sapiens)<400>69cagaagcttc gccgccctca cgatgactac 30<210>70<211>33<212>DNA<213>智人(Homo sapiens)<400>70cgcgaattcg cagtaacttt ccaactcccg gct 33<210>71<211>30<212>DNA<213>智人(Homo sapiens)<400>71tatgaattca gatgctctaa acgtccctgc 30<210>72<211>30<212>DNA<213>智人(Homo sapiens)<400>72tccggatcca cctgcacctg cgcctgcacc 30<210>73<211>30<212>DNA<213>智人(Homo sapiens)<400>73aggaagcttt taggtgggaa aaaaaatcta 30<210>74<211>31<212>DNA<213>智人(Homo sapiens)<400>74ccggaattca aggggcaaaa tcaagggtca a 31<210>75<211>32<212>DNA<213>智人(Homo sapiens)<400>75gccaaggtta gccaccatga acacttcagc cc 32<210>76<211>33<212>DNA<213>智人(Homo sapiens)<400>76ggagaattcg cattggcggg agggagtgcg gtg 33<210>77<211>33<212>DNA<213>智人(Homo sapiens)<400>77atcaccatga ataactcaac aaactcctct aac 33<210>78<211>33<212>DNA<213>智人(Homo sapiens)<400>78gatgaattcc cttgtagcgc ctatgttctt ata 33<210>79<211>32<212>DNA<213>智人(Homo sapiens)<400>79atcaccatga ccttgcacaa taacagtaca ac 32<210>80<211>33<212>DNA<213>智人(Homo sapiens)<400>80ctcgaaattc caaggcctgc tcgggtgcgc gct 33<210>81<211>29<212>DNA<213>智人(Homo sapiens)<400>81atcaccatgg ccaacttcac acctgtcaa 29<210>82<211>33<212>DNA<213>智人(Homo sapiens)<400>82gccgaattcc ctggcagtgc cgatgttccg ata 33<210>83<211>30<212>DNA<213>智人(Homo sapiens)<400>83atcaccatgg aaggggattc ttaccacaat 30<210>84<211>33<212>DNA<213>智人(Homo sapiens)<400>84gacggatccg ggtagcttgc tgttcccctg cca 33<210>85<211>30<212>DNA<213>智人(Homo sapiens)<400>85caggaattct gacagcaatg aatgcttcgt 30<210>86<211>33<212>DNA<213>智人(Homo sapiens)<400>86aatggatcct atcccaagtt catgccgttg cag 33<210>87<211>31<212>DNA<213>智人(Homo sapiens)<400>87agtaagcttt acgcctagct tcgaaatgga t 31<210>88<211>33<212>DNA<213>智人(Homo sapiens)<400>88tgtgaattcg gagagcacat tggaggagaa gct 33<210>89<211>35<212>DNA<213>智人(Homo sapiens)<400>89tccaagctta gaagcagcca tggggacctg tgaca 35<210>90<211>35<212>DNA<213>智人(Homo sapiens)<400>90aacgaattca atttcaacat gagttttggt ggggg 35<210>91<211>27<212>DNA<213>智人(Homo sapiens)<400>91atctgcagac cggtggcgat ggccact 27<210>92<211>35<212>DNA<213>智人(Homo sapiens)<400>92atgggatcca gaatattcat ccacagaggt atagg 35<210>93<211>31<212>DNA<213>智人(Homo sapiens)<400>93tgagaattcc agcggactct gctggaaagg a 31<210>94<211>30<212>DNA<213>智人(Homo sapiens)<400>94gttggatcca ggtagtgagt tgaatggcca 30<210>95<211>31<212>DNA<213>智人(Homo sapiens)<400>95ggaaagcttc aagaaagact ataatatgga t 31<210>96<211>32<212>DNA<213>智人(Homo sapiens)<400>96ggaggatcca gtgagaatta ttacatatga ag 32<210>97<211>33<212>DNA<213>智人(Homo sapiens)<400>97cggaagcttg cagccatgga accggccccc tcc 33<210>98<211>33<212>DNA<213>智人(Homo sapiens)<400>98gccgaattcg gcggcagcgc caccgccggg acc 33<210>99<211>31<212>DNA<213>智人(Homo sapiens)<400>99agtaagcttg cagggcagtg gcatggagcc c 31<210>100<211>33<212>DNA<213>智人(Homo sapiens)<400>100gccgaattct gcgggccgcg gtaccgtctc aga 33<210>101<211>35<212>DNA<213>智人(Homo sapiens)<400>101tttaagcttg cagcactcac catggaatcc ccgat 35<210>102<211>28<212>DNA<213>智人(Homo sapiens)<400>102ctactggttt attcatccca tcgatgtc 28<210>103<211>30<212>DNA<213>智人(Homo sapiens)<400>103accaagcttg agcccgtgat gtccggcacc 30<210>104<211>29<212>DNA<213>智人(Homo sapiens)<400>104cagggatcct tgtcatatga ataaatatt 29<210>105<211>33<212>DNA<213>智人(Homo sapiens)<400>105agtaagcttg gccaagaagt gtcatggctg gtg 33<210>106<211>33<212>DNA<213>智人(Homo sapiens)<400>106catgaattcg gtggccagat tgtcagcagg gag 33<210>107<211>31<212>DNA<213>智人(Homo sapiens)<400>107ctgaagcttc cagcccacag caatggagcc a 31<210>108<211>36<212>DNA<213>智人(Homo sapiens)<400>108caggaattca tttttgaggg aattgccagg gatctg 36<210>109<211>29<212>DNA<213>智人(Homo sapiens)<400>109atcgccatga gcccttgcgg gcccctcaa 29<210>110<211>33<212>DNA<213>智人(Homo sapiens)<400>110ttggaattcg aagtggctga ggccgctgtg ccg 33<210>111<211>31<212>DNA<213>智人(Homo sapiens)<400>111gcaaagcttt tccaggcacc ccaccatggg c 31<210>112<211>33<212>DNA<213>智人(Homo sapiens)<400>112ctggaattca aggtcagcct gtttactggc atc 33<210>113<211>27<212>DNA<213>智人(Homo sapiens)<400>113atcatcatgt ccactcccgg ggtcaat 27<210>114<211>37<212>DNA<213>智人(Homo sapiens)<400>114tgcgaattct atacattttt ctgataagtt cagtgtt 37<210>115<211>30<212>DNA<213>智人(Homo sapiens)<400>115ctgaagcttc ctacagccgt tccgggcatg 30<210>116<211>26<212>DNA<213>智人(Homo sapiens)<400>116cgagaacatc ctcagtttct ccttgg 26<210>117<211>32<212>DNA<213>智人(Homo sapiens)<400>117gggaagcttg cgggcaccat gcgtccccac ct 32<210>118<211>33<212>DNA<213>智人(Homo sapiens)<400>118agcgaattcg atgatgctgg tcctgcaggt gcc 33<210>119<211>31<212>DNA<213>智人(Homo sapiens)<400>119gccgaattca gctgggatgt tccccaatgg c 31<210>120<211>31<212>DNA<213>智人(Homo sapiens)<400>120cagggatcct gcgtggcccg ggctcagagc g 31<210>121<211>31<212>DNA<213>智人(Homo sapiens)<400>121acggaattcc cctcagccat ggacatgctt c 31<210>122<211>29<212>DNA<213>智人(Homo sapiens)<400>122tgggatcccc aggcccctac aggtagctg 29<210>123<211>31<212>DNA<213>智人(Homo sapiens)<400>123gccgaattca gctgccctgc gccggcaccc c 31<210>124<211>31<212>DNA<213>智人(Homo sapiens)<400>124gagggatcca cgcagggtgg gtaggggaag g 31<210>125<211>30<212>DNA<213>智人(Homo sapiens)<400>125tctaagcttg cagagcctga cgcaccccag 30<210>126<211>31<212>DNA<213>智人(Homo sapiens)<400>126cctgaattcc tgggggtgac acggggccgc c 31<210>127<211>30<212>DNA<213>智人(Homo sapiens)<400>127ggcgaattcg gaggatggag aaatagcccc 30<210>128<211>30<212>DNA<213>智人(Homo sapiens)<400>128gtaggatccc ctaccattgt gagtagtgta 30<210>129<211>32<212>DNA<213>智人(Homo sapiens)<400>129ccgaagcttc agggcagacc atgcgcccgc ca 32<210>130<211>33<212>DNA<213>智人(Homo sapiens)<400>130tgggaattcg accagggaga cttcggcttg gaa 33<210>131<211>36<212>DNA<213>智人(Homo sapiens)<400>131gctaagcttg ccatgcggac gctgctgcct cccgcg 36<210>132<211>33<212>DNA<213>智人(Homo sapiens)<400>132gtggaattcg atgaccgagg tctccgtttg cag 33<210>133<211>29<212>DNA<213>智人(Homo sapiens)<400>133atcaccatgc gtctctccgc cggtcccga 29<210>134<211>25<212>DNA<213>智人(Homo sapiens)<400>134ttgttcacct cgatcatgga gaaga 25<210>135<211>24<212>DNA<213>智人(Homo sapiens)<400>135cgcagtactt cgtcttctcc atga 24<210>136<211>35<212>DNA<213>智人(Homo sapiens)<400>136caagaattca gttgaaacag gaatgaattt gatgg 35<210>137<211>35<212>DNA<213>智人(Homo sapiens)<400>137acagaattct ccagttctca ttttcttatc cgtac 35<210>138<211>30<212>DNA<213>智人(Homo sapiens)<400>138gcaaagcttg ctcatggatt ctgggcctct 30<210>139<211>33<212>DNA<213>智人(Homo sapiens)<400>139tctgaattca aagatgatgg tctcagcggt gcc 33<210>140<211>35<212>DNA<213>智人(Homo sapiens)<400>140caagaattca gttgaaacag gaatgaattt gatgg 35<210>141<211>37<212>DNA<213>智人(Homo sapiens)<400>141gccaagatcc gcacgaagaa gatgactttt gtgatcg 37<210>142<211>27<212>DNA<213>智人(Homo sapiens)<400>142cataagcttt cccgccaccc tatcact 27<210>143<211>28<212>DNA<213>智人(Homo sapiens)<400>143actgaattct gctcaatcca gctcccca 28<210>144<211>31<212>DNA<213>智人(Homo sapiens)<400>144cctcggatat catggtccca gagccgggcc c 31<210>145<211>32<212>DNA<213>智人(Homo sapiens)<400>145cagctctaga ttggccagcc ccaagcccgg gt 32<210>146<211>31<212>DNA<213>智人(Homo sapiens)<400>146cctgaattcc agcccgaaat gctgccgcca g 31<210>147<211>26<212>DNA<213>智人(Homo sapiens)<400>147ggtccacgct gatgacgcac aggttc 26<210>148<211>26<212>DNA<213>智人(Homo sapiens)<400>148gaacctgtgc gtcatcagcg tggacc 26<210>149<211>28<212>DNA<213>智人(Homo sapiens)<400>149tgcggatcca tgagggggtt tcttaatg 28<210>150<211>29<212>DNA<213>智人(Homo sapiens)<400>150cggaagcttc tggagcaggt agcagcatg 29<210>151<211>25<212>DNA<213>智人(Homo sapiens)<400>151tgggcaatag ttgtgcattg agcca 25<210>152<211>26<212>DNA<213>智人(Homo sapiens)<400>152ctaatttggt cctacccagc aatggc 26<210>153<211>36<212>DNA<213>智人(Homo sapiens)<400>153cttggatcca gatgagctgt atttattact ggaacg 36<210>154<211>33<212>DNA<213>智人(Homo sapiens)<400>154aataagcttc aagatggaaa ccctttgcct cag 33<210>155<211>26<212>DNA<213>智人(Homo sapiens)<400>155cgttcatgct gtccttatgg ctgctc 26<210>156<211>34<212>DNA<213>智人(Homo sapiens)<400>156gcaggctgtc gacctcgtcc tcaccaccat ggtc 34<210>157<211>37<212>DNA<213>智人(Homo sapiens)<400>157aatgggctca cagcctgtta gatctgcatt gggccac 37<210>158<211>28<212>DNA<213>智人(Homo sapiens)<400>158taacaggctg tgagcccatt cctgtgcg 28<210>159<211>34<212>DNA<213>智人(Homo sapiens)<400>159ttagaattcg cattccctgc ccctgccttc tttc 34<210>160<211>33<212>DNA<213>智人(Homo sapiens)<400>160tgcgaattct aatggcaagt ctgtgteatg gtc 33<210>161<211>33<212>DNA<213>智人(Homo sapiens)<400>161tccggatccc agggtggaag agctttgctt gta 33<210>162<211>30<212>DNA<213>智人(Homo sapiens)<400>162gtgaagcttg cctctggtgc ctgcaggagg 30<210>163<211>31<212>DNA<213>智人(Homo sapiens)<400>163gcagaattcc cggtggcgtg ttgtggtgcc c 31<210>164<211>24<212>DNA<213>智人(Homo sapiens)<400>164catgagctgg tggatcatga aggg 24<210>165<211>24<212>DNA<213>智人(Homo sapiens)<400>165atgaagggca tgcccaggag aaag 24<210>166<211>30<212>DNA<213>智人(Homo sapiens)<400>166cccaagcttc cagccccgga ggcgccggac 30<210>167<211>37<212>DNA<213>智人(Homo sapiens)<400>167tgaaggtgtt gacctgtatg acgaccttga cggtggg 37<210>168<211>37<212>DNA<213>智人(Homo sapiens)<400>168ggtcgtcata caggtcaaca ccttcatgtc cttcata 37<210>169<211>33<212>DNA<213>智人(Homo sapiens)<400>169cacgaattcg tacagcgtct cgcgggtggc att 33<210>170<211>26<212>DNA<213>智人(Homo sapiens)<400>170atcaccatgc gcctcaacag ctccgc 26<210>171<211>30<212>DNA<213>智人(Homo sapiens)<400>171cccaagcttc cagccccgga ggcgccggac 30<210>172<211>37<212>DNA<213>智人(Homo sapiens)<400>172tgaaggtgtt gacctgtatg acgaccttga cggtggg 37<210>173<211>37<212>DNA<213>智人(Homo sapiens)<400>173ggtcgtcata caggtcaaca ccttcatgtc cttcata 37<210>174<211>33<212>DNA<213>智人(Homo sapiens)<400>174cacgaattcg tacagcgtct cgcgggtggc att 33<210>175<211>34<212>DNA<213>智人(Homo sapiens)<400>175cccaagcttc agtaccatgg acagcagcgc tgcc 34<210>176<211>39<212>DNA<213>智人(Homo sapiens)<400>176catcttggtg tatctgacaa tcacatacat gaccaggaa 39<210>177<211>39<212>DNA<213>智人(Homo sapiens)<400>177gtatgtgatt gtcagataca ccaagatgaa gactgccac 39<210>178<211>39<212>DNA<213>智人(Homo sapiens)<400>178tacaatctat ggaaccttgc ctgtattttg ttgtagcca 39<210>179<211>39<212>DNA<213>智人(Homo sapiens)<400>179caaaatacag gcaaggttcc atagattgta cactaacat 39<210>180<211>27<212>DNA<213>智人(Homo sapiens)<400>180cgggcaacgg agcagtttct gcttcag 27<210>181<211>31<212>DNA<213>智人(Homo sapiens)<400>181atggaattct gctgcagcgg ctcctgagct c 31<210>182<211>36<212>DNA<213>智人(Homo sapiens)<400>182acggacacag cctgtagata ggggatgacc ttgcag 36<210>183<211>37<212>DNA<213>智人(Homo sapiens)<400>183atcccctatc tacaggctgt gtccgtgtca gtggcag 37<210>184<211>30<212>DNA<213>智人(Homo sapiens)<400>184ggaggatcca gggcagccct cgctcagggc 30<210>185<211>32<212>DNA<213>智人(Homo sapiens)<400>185cgcaagctta ggcggtggcg atggggaccg cc 32<210>186<211>26<212>DNA<213>智人(Homo sapiens)<400>186ggatgtggtc ccattccggc agacag 26<210>187<211>25<212>DNA<213>智人(Homo sapiens)<400>187aggaggcacc cactggcagc aggta 25<210>188<211>33<212>DNA<213>智人(Homo sapiens)<400>188gccgaattcc atgactgtct cccactcttc ctg 33<210>189<211>32<212>DNA<213>智人(Homo sapiens)<400>189cgagagagga agacaaagaa gacgctgggc at 32<210>190<211>32<212>DNA<213>智人(Homo sapiens)<400>190atgcccagcg tcttctttgt cttcctctct cg 32<210>191<211>32<212>DNA<213>智人(Homo sapiens)<400>191gggagcgcaa agccaagaag accctaggga tc 32<210>192<211>32<212>DNA<213>智人(Homo sapiens)<400>192gatccctagg gtcttcttgg ctttgcgctc cc 32<210>193<211>37<212>DNA<213>智人(Homo sapiens)<400>193cgagaaagga aagccaagaa aatcctgggc atcattc 37<210>194<211>37<212>DNA<213>智人(Homo sapiens)<400>194gaatgatgcc caggattttc ttggctttcc tttctcg 37<210>195<211>32<212>DNA<213>智人(Homo sapiens)<400>195agggaacgga aggcaaaacg catcctgggg ct 32<210>196<211>32<212>DNA<213>智人(Homo sapiens)<400>196agccccagga tgcgttttgc cttccgttcc ct 32<210>197<211>38<212>DNA<213>智人(Homo sapiens)<400>197caagagaacg gaaagcaaag actaccctgg gattaatc 38<210>198<211>38<212>DNA<213>智人(Homo sapiens)<400>198gattaatccc agggtagtct ttgctttccg ttctcttg 38<210>199<211>34<212>DNA<213>智人(Homo sapiens)<400>199aacgaacaga gagccaaaaa ggtcctaggg attg 34<210>200<211>34<212>DNA<213>智人(Homo sapiens)<400>200caatccctag gacctttttg gctctctgtt cgtt 34<210>201<211>35<212>DNA<213>智人(Homo sapiens)<400>201ggacagagac caaagcaaag aagaccctgt gcatc 35<210>202<211>35<212>DNA<213>智人(Homo sapiens)<400>202gatgcacagg gtcttctttg ctttggtctc tgtcc 35<210>203<211>35<212>DNA<213>智人(Homo sapiens)<400>203ggacagagac caaagcaaag aagaccctgt gcatc 35<210>204<211>35<212>DNA<213>智人(Homo sapiens)<400>204gatgcacagg gtcttctttg ctttggtctc tgtcc 35<210>205<211>35<212>DNA<213>智人(Homo sapiens)<400>205ggacagagac caaagcaaag aagaccctgt gcatc 35<210>206<211>35<212>DNA<213>智人(Homo sapiens)<400>206gatgcacagg gtcttctttg ctttggtctc tgtcc 35<210>207<211>35<212>DNA<213>智人(Homo sapiens)<400>207ggacagagac caaagcaaag aagaccctgt gcatc 35<210>208<211>35<212>DNA<213>智人(Homo sapiens)<400>208gatgcacagg gtcttctttg ctttggtctc tgtcc 35<210>209<211>35<212>DNA<213>智人(Homo sapiens)<400>209ggacagagac caaagcaaag aagaccctgt gcatc 35<210>210<211>35<212>DNA<213>智人(Homo sapiens)<400>210gatgcacagg gtcttctttg ctttggtctc tgtcc 35<210>211<211>33<212>DNA<213>智人(Homo sapiens)<400>211aaggagcagc gggccaagct catggtgggc atc 33<210>212<211>33<212>DNA<213>智人(Homo sapiens)<400>212gatgcccacc atgagcttgg cccgctgctc ctt 33<210>213<211>37<212>DNA<213>智人(Homo sapiens)<400>213ctgaaggcca agcttacgct gggcatcctg ctgggca 37<210>214<211>38<212>DNA<213>智人(Homo sapiens)<400>214atgcccagcg taagcttggc cttcagggcc ttcctgct 38<210>215<211>35<212>DNA<213>智人(Homo sapiens)<400>215gaacagaaag caaagaccac cctggggatc atcgt 35<210>216<211>35<212>DNA<213>智人(Homo sapiens)<400>216cccagggtgg tctttgcttt ctgttctcgc ttaaa 35<210>217<211>37<212>DNA<213>智人(Homo sapiens)<400>217gccaagatcc gcacgaagaa gatgactttt gtgatcg 37<210>218<211>37<212>DNA<213>智人(Homo sapiens)<400>218cgatcacaaa agtcatcttc ttcgtgcgga tcttggc 37<210>219<211>37<212>DNA<213>智人(Homo sapiens)<400>219ggccaagatc cgaacaaaga agatgacctt tgtcatc 37<210>220<211>38<212>DNA<213>智人(Homo sapiens)<400>220cgatgacaaa ggtcatcttc tttgttcgga tcttggcc 38<210>221<211>33<212>DNA<213>智人(Homo sapiens)<400>221gctgtggcca agactaagag gatgacgcta gtg 33<210>222<211>33<212>DNA<213>智人(Homo sapiens)<400>222cactagcgtc atcctcttag tcttggccac agc 33<210>223<211>33<212>DNA<213>智人(Homo sapiens)<400>223cgaaagagaa ttaaaagaac ggtattggtg ttg 33<210>224<211>32<212>DNA<213>智人(Homo sapiens)<400>224aataccgttc ttttaattct ctttcgggat tc 32<210>225<211>37<212>DNA<213>智人(Homo sapiens)<400>225gccgcaagga tagcaagacc aaagcgctga tcctcac 37<210>226<211>37<212>DNA<213>智人(Homo sapiens)<400>226gtgaggatca gcgctttggt cttgctatcc ttgcggc 37<210>227<211>31<212>DNA<213>智人(Homo sapiens)<400>227cggagaggag ggccaaggtg ctagtcctgg t 31<210>228<211>31<212>DNA<213>智人(Homo sapiens)<400>228accaggacta gcaccttggc cctcctctcc g 31<210>229<211>40<212>DNA<213>智人(Homo sapiens)<400>229cgccaagtct cagagcaaaa ccaagcgagt ggccgtggtg 40<210>230<211>40<212>DNA<213>智人(Homo sapiens)<400>230caccacggcc actcgcttgg ttttgctctg agacttggcg 40<210>231<211>33<212>DNA<213>智人(Homo sapiens)<400>231cggtccacca agacaaagaa ggtggtggtg gca 33<210>232<211>33<212>DNA<213>智人(Homo sapiens)<400>232tgccaccacc accttctttg tcttggtgga ccg 33<210>233<211>37<212>DNA<213>智人(Homo sapiens)<400>233cgcatggaca ttaggttaaa gaagaccctg gtcctga 37<210>234<211>37<212>DNA<213>智人(Homo sapiens)<400>234tcaggaccag ggtcttcttt aacctaatgt ccatgcg 37<210>235<211>38<212>DNA<213>智人(Homo sapiens)<400>235ggctggatgt gaggttgaag aagaccctag ggctagtg 38<210>236<211>38<212>DNA<213>智人(Homo sapiens)<400>236cactagccct agggtcttct tcaacctcac atccagcc 38<210>237<211>34<212>DNA<213>智人(Homo sapiens)<400>237gaagaggcat agggcaaaga gagtcatctt cacc 34<210>238<211>34<212>DNA<213>智人(Homo sapiens)<400>238ggtgaagatg actctctttg ccctatgcct cttc 34<210>239<211>41<212>DNA<213>智人(Homo sapiens)<400>239gtaaaaaaaa gtacaaggcc aagcggctca tttttgtcat c 41<210>240<211>41<212>DNA<213>智人(Homo sapiens)<400>240gatgacaaaa atgagccgct tggccttgta ctttttttta c 41<210>241<211>37<212>DNA<213>智人(Homo sapiens)<400>241gaagaggcac agggctaaga ggcttatctt caccatc 37<210>242<211>37<212>DNA<213>智人(Homo sapiens)<400>242gatggtgaag ataagcctct tagccctgtg cctcttc 37<210>243<211>41<212>DNA<213>智人(Homo sapiens)<400>243ccacaacaag accaaggcca agaggttggt gctcattgtg g 41<210>244<211>41<212>DNA<213>智人(Homo sapiens)<400>244ccacaatgag caccaacctc ttggccttgg tcttgttgtg g 41<210>245<211>37<212>DNA<213>智人(Homo sapiens)<400>245tccaagcaca aagccaaaaa agtgaccatc actgtcc 37<210>246<211>37<212>DNA<213>智人(Homo sapiens)<400>246ggacagtgat ggtcactttt ttggctttgt gcttgga 37<210>247<211>32<212>DNA<213>智人(Homo sapiens)<400>247gaaggctgtg aaagcccctc tggtgctgct gc 32<210>248<211>32<212>DNA<213>智人(Homo sapiens)<400>248gcagcagcac cagaggggct ttcacagcct tc 32<210>249<211>36<212>DNA<213>智人(Homo sapiens)<400>249agaagcgcaa ggccaagaag accacagtca tcctca 36<210>250<211>36<212>DNA<213>智人(Homo sapiens)<400>250tgaggatgac tgtggtcttc ttggccttgc gcttct 36<210>251<211>28<212>DNA<213>智人(Homo sapiens)<400>251gagaaactaa agtcaagaag actctgtg 28<210>252<211>31<212>DNA<213>智人(Homo sapiens)<400>252ctccttcggt cctcctatcg ttgtcagaag t 31<210>253<211>27<212>DNA<213>智人(Homo sapiens)<400>253gagaagaaag ccaatcagat gctcgcc 27<210>254<211>27<212>DNA<213>智人(Homo sapiens)<400>254ggcgagcatc tgagtggctt tcttctc 27<210>255<211>27<212>DNA<213>智人(Homo sapiens)<400>255gagaagaagg caaaacaaat ggtggcc 27<210>256<211>27<212>DNA<213>智人(Homo sapiens)<400>256ggccaccatt tgttttgcct tcttctc 27<210>257<211>33<212>DNA<213>智人(Homo sapiens)<400>257aagaaggaga ccaaagttaa aaagaccctg tcg 33<210>258<211>33<212>DNA<213>智人(Homo sapiens)<400>258cgacagggtc tttttaactt tggtctcctt ctt 33<210>259<211>42<212>DNA<213>智人(Homo sapiens)<400>259cagcgtcgag aagtgaaaaa aacagttttc tgcttggttg ta 42<210>260<211>42<212>DNA<213>智人(Homo sapiens)<400>260tacaaccaag cagaaaactg tttttttcac ttctcgacgc tg 42<210>261<211>37<212>DNA<213>智人(Homo sapiens)<400>261cagagacggg aagtgaagaa aaccgtcttt tgcctgg 37<210>262<211>37<212>DNA<213>智人(Homo sapiens)<400>262ccaggcaaaa gacggttttc ttcacttccc gtctctg 37<210>263<211>32<212>DNA<213>智人(Homo sapiens)<400>263aaatccagcc gtcccaaacg ggtcctcact gc 32<210>264<211>32<212>DNA<213>智人(Homo sapiens)<400>264gcagtgagga cccgtttggg acggctggat tt 32<210>265<211>32<212>DNA<213>智人(Homo sapiens)<400>265aaatccagcc gtcccaaacg ggtcctcact gc 32<210>266<211>32<212>DNA<213>智人(Homo sapiens)<400>266gcagtgagga cccgtttggg acggctggat tt 32<210>267<211>30<212>DNA<213>智人(Homo sapiens)<400>267ccaagaaaaa gactaaacag acagttctgg 30<210>268<211>30<212>DNA<213>智人(Homo sapiens)<400>268gccaagcgca aggtgaaacg catgatcctc 30<210>269<211>31<212>DNA<213>智人(Homo sapiens)<400>269gaggatcatg cgtttcacct tgcgcttggc g 31<210>270<211>31<212>DNA<213>智人(Homo sapiens)<400>270aggctggctc gctccccgct gacgctggtg c 31<210>271<211>31<212>DNA<213>智人(Homo sapiens)<400>271gcaccagcgt cagcggggag cgagccagcc t 31<210>272<211>30<212>DNA<213>智人(Homo sapiens)<400>272cggcgccacc gcacgaaaaa gctcatcttc 30<210>273<211>32<212>DNA<213>智人(Homo sapiens)<400>273ggaagcgact taagaagaca gtgctggtgt tt 32<210>274<211>33<212>DNA<213>智人(Homo sapiens)<400>274cagcactgtc ttcttaagtc gcttccggga ttc 33<210>275<211>33<212>DNA<213>智人(Homo sapiens)<400>275aaggagaaga aggcgaaacg gaccctgagt gcc 33<210>276<211>33<212>DNA<213>智人(Homo sapiens)<400>276ggcactcagg gtccgtttcg ccttcttctc ctt 33<210>277<211>34<212>DNA<213>智人(Homo sapiens)<400>277ccgggaaaag aaagtcaaga ggacaatctt ggct 34<210>278<211>34<212>DNA<213>智人(Homo sapiens)<400>278agccaagatt gtcctcttga ctttcttttc ccgg 34<210>279<211>37<212>DNA<213>智人(Homo sapiens)<400>279ggtcaaggag aagaaagcga aacagaccct cagtgcg 37<210>280<211>37<212>DNA<213>智人(Homo sapiens)<400>280cgcactgagg gtctgtttcg ctttcttctc cttgacc 37<210>281<211>32<212>DNA<213>智人(Homo sapiens)<400>281gggagcgcaa agtgaaacga acgatctttg cc 32<210>282<211>32<212>DNA<213>智人(Homo sapiens)<400>282ggcaaagatc gttcgtttca ctttgcgctc cc 32<210>283<211>36<212>DNA<213>智人(Homo sapiens)<400>283gtcaaagaga ggaaagcaaa acagacactg agtgcc 36<210>284<211>36<212>DNA<213>智人(Homo sapiens)<400>284ggcactcagt gtctgttttg ctttcctctc tttgac 36<210>285<211>37<212>DNA<213>智人(Homo sapiens)<400>285gcaacactca tgtatgaagg ggaaagtcac catcacc 37<210>286<211>33<212>DNA<213>智人(Homo sapiens)<400>286gccaagcgca aggtgaagaa aatgatgatt gtc 33<210>287<211>33<212>DNA<213>智人(Homo sapiens)<400>287gacaatcatc attttcttca ccttgcgctt ggc 33<210>288<211>32<212>DNA<213>智人(Homo sapiens)<400>288gccaagaaga agtttaagaa gaccatggtg ct 32<210>289<211>32<212>DNA<213>智人(Homo sapiens)<400>289agcaccatgg tcttcttaaa cttcttcttg gc 32<210>290<211>35<212>DNA<213>智人(Homo sapiens)<400>290ggccaaaaga aaggttaaga aaatgatgat tattg 35<210>291<211>35<212>DNA<213>智人(Homo sapiens)<400>291caataatcat cattttctta acctttcttt tggcc 35<210>292<211>30<212>DNA<213>智人(Homo sapiens)<400>292cacggaaacg cctgaaaaaa attgtgcttg 30<210>293<211>30<212>DNA<213>智人(Homo sapiens)<400>293caagcacaat ttttttcagg cgtttccgtg 30<210>294<211>41<212>DNA<213>智人(Homo sapiens)<400>294gaataaaaaa gagatcacga agtgttaagt acagactgac c 41<210>295<211>39<212>DNA<213>智人(Homo sapiens)<400>295ggtcagtctg tacttaacac ttcgtgatct cttttttat 39<210>296<211>32<212>DNA<213>智人(Homo sapiens)<400>296gccctgcggc acggcaagcg cgtcctacgt gc 32<210>297<211>32<212>DNA<213>智人(Homo sapiens)<400>297gcacgtagga cgcgcttgcc gtgccgcagg gc 32<210>298<211>33<212>DNA<213>智人(Homo sapiens)<400>298agcctccagc gcagcaagca ggttctcaga gcc 33<210>299<211>33<212>DNA<213>智人(Homo sapiens)<400>299ggctctgaga acctgcttgc tgcgctggag gct 33<210>300<211>31<212>DNA<213>智人(Homo sapiens)<400>300gcctgcggcg catcaagcgc atggtgctgg t 31<210>301<211>31<212>DNA<213>智人(Homo sapiens)<400>301accagcacca tgcgcttgat gcgccgcagg c 31<210>302<211>32<212>DNA<213>智人(Homo sapiens)<400>302acctgcggcg catcaagcgg ctggtgctgg tg 32<210>303<211>32<212>DNA<213>智人(Homo sapiens)<400>303caccagcacc agccgcttga tgcgccgcag gt 32<210>304<211>32<212>DNA<213>智人(Homo sapiens)<400>304acctgcgtag gatcaagaga ctggtcctgg tg 32<210>305<211>32<212>DNA<213>智人(Homo sapiens)<400>305caccaggacc agtctcttga tcctacgcag gt 32<210>306<211>36<212>DNA<213>智人(Homo sapiens)<400>306gggaatcttc gaaggatcaa gaggatggtg ctggtg 36<210>307<211>35<212>DNA<213>智人(Homo sapiens)<400>307caccagcacc atcctcttga tccttcgaag attcc 35<210>308<211>27<212>DNA<213>智人(Homo sapiens)<400>308cgagactgcg tacctgatga ttagttc 27<210>309<211>36<212>DNA<213>智人(Homo sapiens)<400>309gggaatcttc gaaggatcaa gaggatggtg ctggtg 36<210>310<211>28<212>DNA<213>智人(Homo sapiens)<400>310cggaggaaga caaaaaagat gctgatgg 28<210>311<211>28<212>DNA<213>智人(Homo sapiens)<400>311ccatcagcat cttttttgtc ttcctccg 28<210>312<211>29<212>DNA<213>智人(Homo sapiens)<400>312ccagaaggaa aacaaaacgg atgttgatg 29<210>313<211>31<212>DNA<213>智人(Homo sapiens)<400>313cgactggccc ggtcccccct gctgctcatc c 31<210>314<211>31<212>DNA<213>智人(Homo sapiens)<400>314ggatgagcag caggggggac cgggccagtc g 31<210>315<211>32<212>DNA<213>智人(Homo sapiens)<400>315gtcaagcgcc gggcgaagtg gatggtgtgc ac 32<210>316<211>32<212>DNA<213>智人(Homo sapiens)<400>316gtgcacacca tccacttcgc ccggcgcttg ac 32<210>317<211>32<212>DNA<213>智人(Homo sapiens)<400>317cacgacgtgg agatgaaggg ccagcttgtc gg 32<210>318<211>32<212>DNA<213>智人(Homo sapiens)<400>318ccgacaagct ggcccttcat ctccacgtcg tg 32<210>319<211>36<212>DNA<213>智人(Homo sapiens)<400>319gaggagacgg accacaagat tctcctggct atcatg 36<210>320<211>36<212>DNA<213>智人(Homo sapiens)<400>320catgatagcc aggagaatct tgtggtccgt ctcctc 36<210>321<211>36<212>DNA<213>智人(Homo sapiens)<400>321gccgagatcc agatgaagat cttactcatt gccacc 36<210>322<211>36<212>DNA<213>智人(Homo sapiens)<400>322ggtggcaatg agtaagatct tcatctggat ctcggc 36<210>323<211>33<212>DNA<213>智人(Homo sapiens)<400>323ggaagctgct caaatccccg ctggtgctca tgc 33<210>324<211>33<212>DNA<213>智人(Homo sapiens)<400>324gcatgagcac cagcggggat ttgagcagct tcc 33<210>325<211>33<212>DNA<213>智人(Homo sapiens)<400>325ggaaactggc caaatcgcca ctggtcctgg tcc 33<210>326<211>33<212>DNA<213>智人(Homo sapiens)<400>326ggaccaggac cagtggcgat ttggccagtt tcc 33<210>327<211>31<212>DNA<213>智人(Homo sapiens)<400>327cgcctggcca ggtcccctct cctgctgatc c 31<210>328<211>31<212>DNA<213>智人(Homo sapiens)<400>328ggatcagcag gagaggggac ctggccaggc g 31<210>329<211>29<212>DNA<213>智人(Homo sapiens)<400>329cgagcgcaag atcaaattaa tggtgatgg 29<210>330<211>32<212>DNA<213>智人(Homo sapiens)<400>330agaagaaggt caaacgaatg gtgtccatcg tg 32<210>331<211>32<212>DNA<213>智人(Homo sapiens)<400>331ggacaccatt cgtttgacct tcttctcaga ct 32<210>332<211>30<212>DNA<213>智人(Homo sapiens)<400>332gaacgcaggg tcaagcgcat ggtggtggcc 30<210>333<211>29<212>DNA<213>智人(Homo sapiens)<400>333cggagaagaa aatcaaaagg ctggtgctg 29<210>334<211>35<212>DNA<213>智人(Homo sapiens)<400>334tcggagcgaa aggtgaagcg catggtgttg gtggt 35<210>335<211>35<212>DNA<213>智人(Homo sapiens)<400>335accatgcgct tcacctttcg ctccgagcgc cgccg 35<210>336<211>31<212>DNA<213>智人(Homo sapiens)<400>336aggctagcca ggtccccact cctgctgatc c 31<210>337<211>31<212>DNA<213>智人(Homo sapiens)<400>337ggatcagcag gagtggggac ctggctagcc t 31<210>338<211>31<212>DNA<213>智人(Homo sapiens)<400>338aggctggcca agtccccgct cctgcttatc c 31<210>339<211>31<212>DNA<213>智人(Homo sapiens)<400>339ggataagcag gagcggggac ttggccagcc t 31<210>340<211>34<212>DNA<213>智人(Homo sapiens)<400>340gcaggctgtc gacctcgtcc tcaccaccat ggtc 34<210>341<211>37<212>DNA<213>智人(Homo sapiens)<400>341aatgggctca cagcctgtta gatctgcatt gggccac 37<210>342<211>28<212>DNA<213>智人(Homo sapiens)<400>342taacaggctg tgagcccatt cctgtgcg 28<210>343<211>34<212>DNA<213>智人(Homo sapiens)<400>343ttagaattcg cattccctgc ccctgccttc tttc 34<210>344<211>33<212>DNA<213>智人(Homo sapiens)<400>344tgcgaattct aatggcaagt ctgtgtcatg gtc 33<210>345<211>34<212>DNA<213>智人(Homo sapiens)<400>345tgcggatcct cttcggaaga tgttgaggaa agtg 34<210>346<211>2634<212>DNA<213>智人(Homo sapiens)<400>346atggtcgggc tccttttgtt ttttttccca gcgatctttt tggaggtgtc ccttctcccc 60agaagccccg gcaggaaagt gttgctggca ggagcgtcgt ctcagcgctc ggtggccaga 120atggacggag atgtcatcat tggagccctc ttctcagtcc atcaccagcc tccggccgag 180aaagtgcccg agaggaagtg tggggagatc agggagcagt atggcatcca gagggtggag 240gccatgttcc acacgttgga taagatcaac gcggacccgg tcctcctgcc caacatcacc 300ctgggcagtg agatccggga ctcctgctgg cactcttccg tggctctgga acagagcatt 360gagttcatta gggactctct gatttccatt cgagatgaga aggatgggat caaccggtgt 420ctgcctgacg gccagtccct ccccccaggc aggactaaga agcccattgc gggagtgatc 480ggtcccggct ccagctctgt agccattcaa gtgcagaacc tgctccagct cttcgacatc 540ccccagatcg cttattcagc cacaagcatc gacctgagtg acaaaacttt gtacaaatac 600ttcctgaggg ttgtcccttc tgacactttg caggcaaggg ccatgcttga catagtcaaa 660cgttacaatt ggacctatgt ctctgcagtc cacacggaag ggaattatgg ggagagcgga 720atggacgctt tcaaagagct ggctgcccag gaaggcctct gtatcgccca ttctgacaaa 780atctacagca acgctgggga gaagagcttt gaccgactct tgcgcaaact ccgagagagg 840cttcccaagg ctagagtggt ggtctgcttc tgtgaaggca tgacagtgcg aggactcctg 900agcgccatgc ggcgccttgg cgtcgtgggc gagttctcac tcattggaag tgatggatgg 960gcagacagag atgaagtcat tgaaggttat gaggtggaag ccaacggggg aatcacgata 1020aagctgcagt ctccagaggt caggtcattt gatgattatt tcctgaaact gaggctggac 1080actaacacga ggaatccctg gttccctgag ttctggcaac atcggttcca gtgccgcctt 1140ccaggacacc ttctggaaaa tcccaacttt aaacgaatct gcacaggcaa tgaaagctta 1200gaagaaaact atgtccagga cagtaagatg gggtttgtca tcaatgccat ctatgccatg 1260gcacatgggc tgcagaacat gcaccatgcc ctctgccctg gccacgtggg cctctgcgat 1320gccatgaagc ccatcgacgg cagcaagctg ctggacttcc tcatcaagtc ctcattcatt 1380ggagtatctg gagaggaggt gtggtttgat gagaaaggag acgctcctgg aaggtatgat 1440atcatgaatc tgcagtacac tgaagctaat cgctatgact atgtgcacgt tggaacctgg 1500catgaaggag tgctgaacat tgatgattac aaaatccaga tgaacaagag tggagtggtg 1560cggtctgtgt gcagtgagcc ttgcttaaag ggccagatta aggttatacg gaaaggagaa 1620gtgagctgct gctggatttg cacggcctgc aaagagaatg aatatgtgca agatgagttc 1680acctgcaaag cttgtgactt gggatggtgg cccaatgcag atctaacagg ctgtgagccc 1740attcctgtgc gctatcttga gtggagcaac atcgaatcca ttatagccat cgccttttca 1800tgcctgggaa tccttgttac cttgtttgtc accctaatct ttgtactgta ccgggacaca 1860ccagtggtca aatcctccag tcgggagctc tgctacatca tcctagctgg catcttcctt 1920ggttatgtgt gcccattcac tctcattgcc aaacctacta ccacctcctg ctacctccag 1980cgcctcttgg ttggcctctc ctctgcgatg tgctactctg ctttagtgac taaaaccaat 2040cgtattgcac gcatcctggc tggcagcaag aagaagatct gcacccggaa gcccaggttc 2100atgagtgcct gggctcaggt gatcattgcc tcaattctga ttagtgtgca actaaccctg 2160gtggtaaccc tgatcatcat ggaaccccct atgcccattc tgtcctaccc aagtatcaag 2220gaagtctacc ttatctgcaa taccagcaac ctgggtgtgg tggccccttt gggctacaat 2280ggactcctca tcatgagctg tacctactat gccttcaaga cccgcaacgt gcccgccaac 2340ttcaacgagg ccaaatatat cgcgttcacc atgtacacca cctgtatcat ctggctagct 2400tttgtgccca tttactttgg gagcaactac aagatcatca caacttgctt tgcagtgagt 2460ctcagtgtaa cagtggctct ggggtgcatg ttcactccca agatgtacat cattattgcc 2520aagcctgaga ggaatgtccg cagtgccttc accacctctg atgttgtccg catgcatgtt 2580ggcgatggca agctgccctg ccgctccaac actttcctca acatcttccg aaga 2634<210>347<211>878<212>PRT<213>智人(Homo sapiens)<400>347Met Val Gly Leu Leu Leu Phe Phe Phe Pro Ala Ile Phe Leu Glu Val1 5 10 15Ser Leu Leu Pro Arg Ser Pro Gly Arg Lys Val Leu Leu Ala Gly Ala
20 25 30Ser Ser Gln Arg Ser Val Ala Arg Met Asp Gly Asp Val Ile Ile Gly
35 40 45Ala Leu Phe Ser Val His His Gln Pro Pro Ala Glu Lys Val Pro Glu
50 55 60Arg Lys Cys Gly Glu Ile Arg Glu Gln Tyr Gly Ile Gln Arg Val Glu65 70 75 80Ala Met Phe His Thr Leu Asp Lys Ile Asn Ala Asp Pro Val Leu Leu
85 90 95Pro Asn Ile Thr Leu Gly Ser Glu Ile Arg Asp Ser Cys Trp His Ser
100 105 110Ser Val Ala Leu Glu Gln Ser Ile Glu Phe Ile Arg Asp Ser Leu Ile
115 120 125Ser Ile Arg Asp Glu Lys Asp Gly Ile Asn Arg Cys Leu Pro Asp Gly
130 135 140Gln Ser Leu Pro Pro Gly Arg Thr Lys Lys Pro Ile Ala Gly Val Ile145 150 155 160Gly Pro Gly Ser Ser Ser Val Ala Ile Gln Val Gln Asn Leu Leu Gln
165 170 175Leu Phe Asp Ile Pro Gln Ile Ala Tyr Ser Ala Thr Ser Ile Asp Leu
180 185 190Ser Asp Lys Thr Leu Tyr Lys Tyr Phe Leu Arg Val Val Pro Ser Asp
195 200 205Thr Leu Gln Ala Arg Ala Met Leu Asp Ile Val Lys Arg Tyr Asn Trp
210 215 220Thr Tyr Val Ser Ala Val His Thr Glu Gly Asn Tyr Gly Glu Ser Gly225 230 235 240Met Asp Ala Phe Lys Glu Leu Ala Ala Gln Glu Gly Leu Cys Ile Ala
245 250 255His Ser Asp Lys Ile Tyr Ser Asn Ala Gly Glu Lys Ser Phe Asp Arg
260 265 270Leu Leu Arg Lys Leu Arg Glu Arg Leu Pro Lys Ala Arg Val Val Val
275 280 285Cys Phe Cys Glu Gly Met Thr Val Arg Gly Leu Leu Ser Ala Met Arg
290 295 300Arg Leu Gly Val Val Gly Glu Phe Ser Leu Ile Gly Ser Asp Gly Trp305 310 315 320Ala Asp Arg Asp Glu Val Ile Glu Gly Tyr Glu Val Glu Ala Asn Gly
325 330 335Gly Ile Thr Ile Lys Leu Gln Ser Pro Glu Val Arg Ser Phe Asp Asp
340 345 350Tyr Phe Leu Lys Leu Arg Leu Asp Thr Asn Thr Arg Asn Pro Trp Phe
355 360 365Pro Glu Phe Trp Gln His Arg Phe Gln Cys Arg Leu Pro Gly His Leu
370 375 380Leu Glu Asn Pro Asn Phe Lys Arg Ile Cys Thr Gly Asn Glu Ser Leu385 390 395 400Glu Glu Asn Tyr Val Gln Asp Ser Lys Met Gly Phe Val Ile Asn Ala
405 410 415Ile Tyr Ala Met Ala His Gly Leu Gln Asn Met His His Ala Leu Cys
420 425 430Pro Gly His Val Gly Leu Cys Asp Ala Met Lys Pro Ile Asp Gly Ser
435 440 445Lys Leu Leu Asp Phe Leu Ile Lys Ser Ser Phe Ile Gly Val Ser Gly
450 455 460Glu Glu Val Trp Phe Asp Glu Lys Gly Asp Ala Pro Gly Arg Tyr Asp465 470 475 480Ile Met Asn Leu Gln Tyr Thr Glu Ala Asn Arg Tyr Asp Tyr Val His
485 490 495Val Gly Thr Trp His Glu Gly Val Leu Asn Ile Asp Asp Tyr Lys Ile
500 505 510Gln Met Asn Lys Ser Gly Val Val Arg Ser Val Cys Ser Glu Pro Cys
515 520 525Leu Lys Gly Gln Ile Lys Val Ile Arg Lys Gly Glu Val Ser Cys Cys
530 535 540Trp Ile Cys Thr Ala Cys Lys Glu Asn Glu Tyr Val Gln Asp Glu Phe545 550 555 560Thr Cys Lys Ala Cys Asp Leu Gly Trp Trp Pro Asn Ala Asp Leu Thr
565 570 575Gly Cys Glu Pro Ile Pro Val Arg Tyr Leu Glu Trp Ser Asn Ile Glu
580 585 590Ser Ile Ile Ala Ile Ala Phe Ser Cys Leu Gly Ile Leu Val Thr Leu
595 600 605Phe Val Thr Leu Ile Phe Val Leu Tyr Arg Asp Thr Pro Val Val Lys
610 615 620Ser Ser Ser Arg Glu Leu Cys Tyr Ile Ile Leu Ala Gly Ile Phe Leu625 630 635 640Gly Tyr Val Cys Pro Phe Thr Leu Ile Ala Lys Pro Thr Thr Thr Ser
645 650 655Cys Tyr Leu Gln Arg Leu Leu Val Gly Leu Ser Ser Ala Met Cys Tyr
660 665 670Ser Ala Leu Val Thr Lys Thr Asn Arg Ile Ala Arg Ile Leu Ala Gly
675 680 685Ser Lys Lys Lys Ile Cys Thr Arg Lys Pro Arg Phe Met Ser Ala Trp
690 695 700Ala Gln Val Ile Ile Ala Ser Ile Leu Ile Ser Val Gln Leu Thr Leu705 710 715 720Val Val Thr Leu Ile Ile Met Glu Pro Pro Met Pro Ile Leu Ser Tyr
725 730 735Pro Ser Ile Lys Glu Val Tyr Leu Ile Cys Asn Thr Ser Asn Leu Gly
740 745 750Val Val Ala Pro Leu Gly Tyr Asn Gly Leu Leu Ile Met Ser Cys Thr
755 760 765Tyr Tyr Ala Phe Lys Thr Arg Asn Val Pro Ala Asn Phe Asn Glu Ala
770 775 780Lys Tyr Ile Ala Phe Thr Met Tyr Thr Thr Cys Ile Ile Trp Leu Ala785 790 795 800Phe Val Pro Ile Tyr Phe Gly Ser Asn Tyr Lys Ile Ile Thr Thr Cys
805 810 815Phe Ala Val Ser Leu Ser Val Thr Val Ala Leu Gly Cys Met Phe Thr
820 825 830Pro Lys Met Tyr Ile Ile Ile Ala Lys Pro Glu Arg Asn ValArg Ser
835 840 845Ala Phe Thr Thr Ser Asp Val Val Arg Met His Val Gly Asp Gly Lys
850 855 860Leu Pro Cys Arg Ser Asn Thr Phe Leu Asn Ile Phe Arg Arg865 870 875<210>348<211>31<212>DNA<213>智人(Homo sapiens)<400>348agagggtgaa acgcacagcc atcgccatct g 31<210>349<211>31<212>DNA<213>智人(Homo sapiens)<400>349ctccttcggt cctcctatcg ttgtcagaag t 31<210>350<211>1062<212>DNA<213>智人(Homo sapiens)<400>350atggacctgg aagcctcgct gctgcccact ggtcccaatg ccagcaacac ctctgatggc 60cccgataacc tcacttcggc aggatcacct cctcgcacgg ggagcatctc ctacatcaac 120atcatcatgc cttcggtgtt cggcaccatc tgcctcctgg gcatcatcgg gaactccacg 180gtcatcttcg cggtcgtgaa gaagtccaag ctgcactggt gcaacaacgt ccccgacatc 240ttcatcatca acctctcggt agtagatctc ctctttctcc tgggcatgcc cttcatgatc 300caccagctca tgggcaatgg ggtgtggcac tttggggaga ccatgtgcac cctcatcacg 360gccatggatg ccaatagtca gttcaccagc acctacatcc tgaccgccat ggccattgac 420cgctacctgg ccactgtcca ccccatctct tccacgaagt tccggaagcc ctctgtggcc 480accctggtga tctgcctcct gtgggccctc tccttcatca gcatcacccc tgtgtggctg 540tatgccagac tcatcccctt cccaggaggt gcagtgggct gcggcatacg cctgcccaac 600ccagacactg acctctactg gttcaccctg taccagtttt tcctggcctt tgccctgcct 660tttgtggtca tcacagccgc atacgtgagg atcctgcagc gcatgacgtc ctcagtggcc 720cccgcctccc agcgcagcat ccggctgcgg acaaagaggg tgaaacgcac agccatcgcc 780atctgtctgg tcttctttgt gtgctgggca ccctactatg tgctacagct gacccagttg 840tccatcagcc gcccgaccct cacctttgtc tacttataca atgcggccat cagcttgggc 900tatgccaaca gctgcctcaa cccctttgtg tacatcgtgc tctgtgagac gttccgcaaa 960cgcttggtcc tgtcggtgaa gcctgcagcc caggggcagc ttcgcgctgt cagcaacgct 1020cagacggctg acgaggagag gacagaaagc aaaggcacct ga 1062<210>351<211>353<212>PRT<213>智人(Homo sapiens)<400>351Met Asp Leu Glu Ala Ser Leu Leu Pro Thr Gly Pro Asn Ala Ser Asn1 5 10 15Thr Ser Asp Gly Pro Asp Asn Leu Thr Ser Ala Gly Ser Pro Pro Arg
20 25 30Thr Gly Ser Ile Ser Tyr Ile Asn Ile Ile Met Pro Ser Val Phe Gly
35 40 45Thr Ile Cys Leu Leu Gly Ile Ile Gly Asn Ser Thr Val Ile Phe Ala
50 55 60Val Val Lys Lys Ser Lys Leu His Trp Cys Asn Asn Val Pro Asp Ile65 70 75 80Phe Ile Ile Asn Leu Ser Val Val Asp Leu Leu Phe Leu Leu Gly Met
85 90 95Pro Phe Met Ile His Gln Leu Met Gly Asn Gly Val Trp His Phe Gly
100 105 110Glu Thr Met Cys Thr Leu Ile Thr Ala Met Asp Ala Asn Ser Gln Phe
115 120 125Thr Ser Thr Tyr Ile Leu Thr Ala Met Ala Ile Asp Arg Tyr Leu Ala
130 135 140Thr Val His Pro Ile Ser Ser Thr Lys Phe Arg Lys Pro Ser Val Ala145 150 155 160Thr Leu Val Ile Cys Leu Leu Trp Ala Leu Ser Phe Ile Ser Ile Thr
165 170 175Pro Val Trp Leu Tyr Ala Arg Leu Ile Pro Phe Pro Gly Gly Ala Val
180 185 190Gly Cys Gly Ile Arg Leu Pro Asn Pro Asp Thr Asp Leu Tyr Trp Phe
195 200 205Thr Leu Tyr Gln Phe Phe Leu Ala Phe Ala Leu Pro Phe Val Val Ile
210 215 220Thr Ala Ala Tyr Val Arg Ile Leu Gln Arg Met Thr Ser Ser Val Ala225 230 235 240Pro Ala Ser Gln Arg Ser Ile Arg Leu Arg Thr Lys Arg Val Lys Arg
245 250 255Thr Ala Ile Ala Ile Cys Leu Val Phe Phe Val Cys Trp Ala Pro Tyr
260 265 270Tyr Val Leu Gln Leu Thr Gln Leu Ser Ile Ser Arg Pro Thr Leu Thr
275 280 285Phe Val Tyr Leu Tyr Asn Ala Ala Ile Ser Leu Gly Tyr Ala Asn Ser
290 295 300Cys Leu Asn Pro Phe Val Tyr Ile Val Leu Cys Glu Thr Phe Arg Lys305 310 315 320Arg Leu Val Leu Ser Val Lys Pro Ala Ala Gln Gly Gln Leu Arg Ala
325 330 335Val Ser Asn Ala Gln Thr Ala Asp Glu Glu Arg Thr Glu Ser Lys Gly
340 345 350Thr<210>352<211>31<212>DNA<213>智人(Homo sapiens)<400>352agagggtgaa acgcagagcc atcgccatct g 31<210>353<211>31<212>DNA<213>智人(Homo sapiens)<400>353cagatggcga tggctctgcg tttcaccctc t 31<210>354<211>1062<212>DNA<213>智人(Homo sapiens)<400>354atggacctgg aagcctcgct gctgcccact ggtcccaatg ccagcaacac ctctgatggc 60cccgataacc tcacttcggc aggatcacct cctcgcacgg ggagcatctc ctacatcaac 120atcatcatgc cttcggtgtt cggcaccatc tgcctcctgg gcatcatcgg gaactccacg 180gtcatcttcg cggtcgtgaa gaagtccaag ctgcactggt gcaacaacgt ccccgacatc 240ttcatcatca acctctcggt agtagatctc ctctttctcc tgggcatgcc cttcatgatc 300caccagctca tgggcaatgg ggtgtggcac tttggggaga ccatgtgcac cctcatcacg 360gccatggatg ccaatagtca gttcaccagc acctacatcc tgaccgccat ggccattgac 420cgctacctgg ccactgtcca ccccatctct tccacgaagt tccggaagcc ctctgtggcc 480accctggtga tctgcctcct gtgggccctc tccttcatca gcatcacccc tgtgtggctg 540tatgccagac tcatcccctt cccaggaggt gcagtgggct gcggcatacg cctgcccaac 600ccagacactg acctctactg gttcaccctg taccagtttt tcctggcctt tgccctgcct 660tttgtggtca tcacagccgc atacgtgagg atcctgcagc gcatgacgtc ctcagtggcc 720cccgcctccc agcgcagcat ccggctgcgg acaaagaggg tgaaacgcca ggccatcgcc 780atctgtctgg tcttctttgt gtgctgggca ccctactatg tgctacagct gacccagttg 840tccatcagcc gcccgaccct cacctttgtc tacttataca atgcggccat cagcttgggc 900tatgccaaca gctgcctcaa cccctttgtg tacatcgtgc tctgtgagac gttccgcaaa 960cgcttggtcc tgtcggtgaa gcctgcagcc caggggcagc ttcgcgctgt cagcaacgct 1020cagacggctg acgaggagag gacagaaagc aaaggcacct ga 1062<210>355<211>353<212>PRT<213>智人(Homo sapiens)<400>355Met Asp Leu Glu Ala Ser Leu Leu Pro Thr Gly Pro Asn Ala Ser Asn1 5 10 15Thr Ser Asp Gly Pro Asp Asn Leu Thr Ser Ala Gly Ser Pro Pro Arg
20 25 30Thr Gly Ser Ile Ser Tyr Ile Asn Ile Ile Met Pro Ser Val Phc Gly
35 40 45Thr Ile Cys Leu Leu Gly Ile Ile Gly Asn Ser Thr Val Ile Phe Ala
50 55 60Val Val Lys Lys Ser Lys Leu His Trp Cys Asn Asn Val Pro Asp Ile65 70 75 80Phe Ile Ile Asn Leu Ser Val Val Asp Leu Leu Phe Leu Leu Gly Met
85 90 95Pro Phe Met Ile His Gln Leu Met Gly Asn Gly Val Trp His Phe Gly
100 105 110Glu Thr Met Cys Thr Leu Ile Thr Ala Met Asp Ala Asn Ser Gln Phe
115 120 125Thr Ser Thr Tyr Ile Leu Thr Ala Met Ala Ile Asp Arg Tyr Leu Ala
130 135 140Thr Val His Pro Ile Ser Ser Thr Lys Phe Arg Lys Pro Ser Val Ala145 150 155 160Thr Leu Val Ile Cys Leu Leu Trp Ala Leu Ser Phe Ile Ser Ile Thr
165 170 175Pro Val Trp Leu Tyr Ala Arg Leu Ile Pro Phe Pro Gly Gly Ala Val
180 185 190Gly Cys Gly Ile Arg Leu Pro Asn Pro Asp Thr Asp Leu Tyr Trp Phe
195 200 205Thr Leu Tyr Gln Phe Phe Leu Ala Phe Ala Leu Pro Phe Val Val Ile
210 215 220Thr Ala Ala Tyr Val Arg Ile Leu Gln Arg Met Thr Ser Ser Val Ala225 230 235 240Pro Ala Ser Gln Arg Ser Ile Arg Leu Arg Thr Lys Arg Val Lys Arg
245 250 255Lys Ala Ile Ala Ile Cys Leu Val Phe Phe Val Cys Trp Ala Pro Tyr
260 265 270Tyr Val Leu Gln Leu Thr Gln Leu Ser Ile Ser Arg Pro Thr Leu Thr
275 280 285Phe Val Tyr Leu Tyr Asn Ala Ala Ile Ser Leu Gly Tyr Ala Asn Ser
290 295 300Cys Leu Asn Pro Phe Val Tyr Ile Val Leu Cys Glu Thr Phe Arg Lys305 310 315 320Arg Leu Val Leu Ser Val Lys Pro Ala Ala Gln Gly Gln Leu Arg Ala
325 330 335Val Ser Asn Ala Gln Thr Ala Asp Glu Glu Arg Thr Glu Ser Lys Gly
340 345 350Thr<210>356<211>70<212>DNA<213>智人(Homo sapiens)<400>356gatcctgcag aaggtgaagt cctctggaat ccgagtgggc tcctctaaga ggaagaagtc 60tgagaagaag 70<210>357<211>71<212>DNA<213>智人(Homo sapiens)<400>357gtgaccttct tctcagactt cttcctctta gaggagccca ctcggattcc agaggacttc 60accttctgca g 71<210>358<211>1349<212>DNA<213>智人(Homo sapiens)<400>358atggacctgg aagcctcgct gctgcccact ggtcccaatg ccagcaacac ctctgatggc 60cccgataacc tcacttcggc aggatcacct cctcgcacgg ggagcatctc ctacatcaac 120atcatcatgc cttcggtgtt cggcaccatc tgcctcctgg gcatcatcgg gaactccacg 180gtcatcttcg cggtcgtgaa gaagtccaag ctgcactggt gcaacaacgt ccccgacatc 240ttcatcatca acctctcggt agtagatctc ctctttctcc tgggcatgcc cttcatgatc 300caccagctca tgggcaatgg ggtgtggcac tttggggaga ccatgtgcac cctcatcacg 360gccatggatg ccaatagtca gttcaccagc acctacatcc tgaccgccat ggccattgac 420cgctacctgg ccactgtcca ccccatctct tccacgaagt tccggaagcc ctctgtggcc 480accctggtga tctgcctcct gtgggccctc tccttcatca gcatcacccc tgtgtggctg 540tatgccagac tcatcccctt cccaggaggt gcagtgggct gcggcatacg cctgcccaac 600ccagacactg acctctactg gttcaccctg taccagtttt tcctggcctt tgccctgcct 660tttgtggtca tcacagccgc atacgtgagg atcctgcaga aggtgaagtc ctctggaatc 720cgagtgggct cctctaagag gaagaagtct gagaagaagg tcacccgcac agccatcgcc 780atctgtctgg tcttctttgt gtgctgggca ccctactatg tgctacagct gacccagttg 840tccatcagcc gcccgaccct cacctttgtc tacttataca atgcggccat cagcttgggc 900tatgccaaca gctgcctcaa cccctttgtg tacatcgtgc tctgtgagac gttccgcaaa 960cgcttggtcc tgtcggtgaa gcctgcagcc caggggcagc ttcgcgctgt cagcaacgct 1020cagacggctg acgaggagag gacagaaagc aaaggcacct gatacttccc ctgccaccct 1080gcacacctcc aagtcagggc accacaacac gccaccggga gagatgctga gaaaaaccca 1140agaccgctcg ggaaatgcag gaaggccggg ttgtgagggg ttgttgcaat gaaataaata 1200cattccatgg gctcacacgt tgctggggag gcctggagtc aggtttgggg ttttcagata 1260tcagaaatcc cttgggggag caggatgaga cctttggata gaacagaagc tgagcaagag 1320aacatgttgg tttggataac cggttgcac 1349<210>359<211>446<212>PRT<213>智人(Homo sapiens)<400>359Met Asp Leu Glu Ala Ser Leu Leu Pro Thr Gly Pro Asn Ala Ser Asn1 5 l0 15Thr Ser Asp Gly Pro Asp Asn Leu Thr Ser Ala Gly Ser Pro Pro Arg
20 25 30Thr Gly Ser Ile Ser Tyr Ile Asn Ile Ile Met Pro Ser Val Phe Gly
35 40 45Thr Ile Cys Leu Leu Gly Ile Ile Gly Asn Ser Thr Val Ile Phe Ala
50 55 60Val Val Lys Lys Ser Lys Leu His Trp Cys Asn Asn Val Pro Asp Ile65 70 75 80Phe Ile Ile Asn Leu Ser Val Val Asp Leu Leu Phe Leu Leu Gly Met
85 90 95Pro Phe Met Ile His Gln Leu Met Gly Asn Gly Val Trp His Phe Gly
100 105 110Glu Thr Met Cys Thr Leu Ile Thr Ala Met Asp Ala Asn Ser Gln Phe
115 120 125Thr Ser Thr Tyr Ile Leu Thr Ala Met Ala Ile Asp Arg Tyr Leu Ala
130 135 140Thr Val His Pro Ile Ser Ser Thr Lys Phe Arg Lys Pro Ser Val Ala145 150 155 160Thr Leu Val Ile Cys Leu Leu Trp Ala Leu Ser Phe Ile Ser Ile Thr
165 170 175Pro Val Trp Leu Tyr Ala Arg Leu Ile Pro Phe Pro Gly Gly Ala Val
180 185 190Gly Cys Gly Ile Arg Leu Pro Asn Pro Asp Thr Asp Leu Tyr Trp Phe
195 200 205Thr Leu Tyr Gln Phe Phe Leu Ala Phe Ala Leu Pro Phe Val Val Ile
210 215 220Thr Ala Ala Tyr Val Arg Ile Leu Gln Lys Val Lys Ser Ser Gly Ile225 230 235 240Arg Val Gly Ser Ser Lys Arg Lys Lys Ser Glu Lys Lys Val Thr Arg
245 250 255Thr Ala Ile Ala Ile Cys Leu Val Phe Phe Val Cys Trp Ala Pro Tyr
260 265 270Tyr Val Leu Gln Leu Thr Gln Leu Ser Ile Ser Arg Pro Thr Leu Thr
275 280 285Phe Val Tyr Leu Tyr Asn Ala Ala Ile Ser Leu Gly Tyr Ala Asn Ser
290 295 300Cys Leu Asn Pro Phe Val Tyr Ile Val Leu Cys Glu Thr Phe Arg Lys305 310 315 320Arg Leu Val Leu Ser Val Lys Pro Ala Ala Gln Gly Gln Leu Arg Ala
325 330 335Val Ser Asn Ala Gln Thr Ala Asp Glu Glu Arg Thr Glu Ser Lys Gly
340 345 350Thr Tyr Phe Pro Cys His Pro Ala His Leu Gln Val Arg Ala Pro Gln
355 360 365His Ala Thr Gly Arg Asp Ala Glu Lys Asn Pro Arg Pro Leu Gly Lys
370 375 380Cys Arg Lys Ala Gly Leu Gly Val Val Ala Met Lys Ile His Ser Met385 390 395 400Gly Ser His Val Ala Gly Glu Ala Trp Ser Gln Val Trp Gly Phe Gln
405 410 415Ile Ser Glu Ile Pro Trp Gly Ser Arg Met Arg Pro Leu Asp Arg Thr
420 425 430Glu Ala Glu Gln Glu Asn Met Leu Val Trp Ile Thr Gly Cys
435 440 445<210>360<211>33<212>DNA<213>智人(Homo sapiens)<400>360ggctatgcca acagctacct caaccccttt gtg 33<210>361<211>33<212>DNA<213>智人(Homo sapiens)<400>361cacaaagggg ttgaggtagc tgttggcata gcc 33<210>362<211>1062<212>DNA<213>智人(Homo sapiens)<400>362atggacctgg aagcctcgct gctgcccact ggtcccaatg ccagcaacac ctctgatggc 60cccgataacc tcacttcggc aggatcacct cctcgcacgg ggagcatctc ctacatcaac 120atcatcatgc cttcggtgtt cggcaccatc tgcctcctgg gcatcatcgg gaactccacg 180gtcatcttcg cggtcgtgaa gaagtccaag ctgcactggt gcaacaacgt ccccgacatc 240ttcatcatca acctctcggt agtagatctc ctctttctcc tgggcatgcc cttcatgatc 300caccagctca tgggcaatgg ggtgtggcac tttggggaga ccatgtgcac cctcatcacg 360gccatggatg ccaatagtca gttcaccagc acctacatcc tgaccgccat ggccattgac 420cgctacctgg ccactgtcca ccccatctct tccacgaagt tccggaagcc ctctgtggcc 480accctggtga tctgcctcct gtgggccctc tccttcatca gcatcacccc tgtgtggctg 540tatgccagac tcatcccctt cccaggaggt gcagtgggct gcggcatacg cctgcccaac 600ccagacactg acctctactg gttcaccctg taccagtttt tcctggcctt tgccctgcct 660tttgtggtca tcacagccgc atacgtgagg atcctgcagc gcatgacgtc ctcagtggcc 720cccgcctccc agcgcagcat ccggctgcgg acaaagaggg tgacccgcac agccatcgcc 780atctgtctgg tcttctttgt gtgctgggca ccctactatg tgctacagct gacccagttg 840tccatcagcc gcccgaccct cacctttgtc tacttataca atgcggccat cagcttgggc 900tatgccaaca gctacctcaa cccctttgtg tacatcgtgc tctgtgagac gttccgcaaa 960cgcttggtcc tgtcggtgaa gcctgcagcc caggggcagc ttcgcgctgt cagcaacgct 1020cagacggctg acgaggagag gacagaaagc aaaggcacct ga 1062<210>363<211>353<212>PRT<213>智人(Homo sapiens)<400>363Met Asp Leu Glu Ala Ser Leu Leu Pro Thr Gly Pro Asn Ala Ser Asn1 5 10 15Thr Ser Asp Gly Pro Asp Asn Leu Thr Ser Ala Gly Ser Pro Pro Arg
20 25 30Thr Gly Ser Ile Ser Tyr Ile Asn Ile Ile Met Pro Ser Val Phe Gly
35 40 45Thr Ile Cys Leu Leu Gly Ile Ile Gly Asn Ser Thr Val Ile Phe Ala
50 55 60Val Val Lys Lys Ser Lys Leu His Trp Cys Asn Asn Val Pro Asp Ile65 70 75 80Phe Ile Ile Asn Leu Ser Val Val Asp Leu Leu Phe Leu Leu Gly Met
85 90 95Pro Phe Met Ile His Gln Leu Met Gly Asn Gly Val Trp His Phe Gly
100 105 110Glu Thr Met Cys Thr Leu Ile Thr Ala Met Asp Ala Asn Ser Gln Phe
115 120 125Thr Ser Thr Tyr Ile Leu Thr Ala Met Ala Ile Asp Arg Tyr Leu Ala
130 135 140Thr Val His Pro Ile Ser Ser Thr Lys Phe Arg Lys Pro Ser Val Ala145 150 155 160Thr Leu Val Ile Cys Leu Leu Trp Ala Leu Ser Phe Ile Ser Ile Thr
165 170 175Pro Val Trp Leu Tyr Ala Arg Leu Ile Pro Phe Pro Gly Gly Ala Val
180 185 190Gly Cys Gly Ile Arg Leu Pro Asn Pro Asp Thr Asp Leu Tyr Trp Phe
195 200 205Thr Leu Tyr Gln Phe Phe Leu Ala Phe Ala Leu Pro Phe Val Val Ile
210 215 220Thr Ala Ala Tyr Val Arg Ile Leu Gln Arg Met Thr Ser Ser Val Ala225 230 235 240Pro Ala Ser Gln Arg Ser Ile Arg Leu Arg Thr Lys Arg Val Thr Arg
245 250 255Thr Ala Ile Ala Ile Cys Leu Val Phe Phe Val Cys Trp Ala Pro Tyr
260 265 270Tyr Val Leu Gln Leu Thr Gln Leu Ser Ile Ser Arg Pro Thr Leu Thr
275 280 285Phe Val Tyr Leu Tyr Asn Ala Ala Ile Ser Leu Gly Tyr Ala Asn Ser
290 295 300Tyr Leu Asn Pro Phe Val Tyr Ile Val Leu Cys Glu Thr Phe Arg Lys305 310 315 320Arg Leu Val Leu Ser Val Lys Pro Ala Ala Gln Gly Gln Leu Arg Ala
325 330 335Val Ser Asn Ala Gln Thr Ala Asp Glu Glu Arg Thr Glu Ser Lys Gly
340 345 350Thr<210>364<211>33<212>DNA<213>智人(Homo sapiens)<400>364ttgtgtgctg ggcactctac tatgtgctac agc 33<210>365<211>33<212>DNA<213>智人(Homo sapiens)<400>365gctgtagcac atagtagagt gcccagcaca caa 33<210>366<211>1062<212>DNA<213>智人(Homo sapiens)<400>366atggacctgg aagcctcgct gctgcccact ggtcccaatg ccagcaacac ctctgatggc 60cccgataacc tcacttcggc aggatcacct cctcgcacgg ggagcatctc ctacatcaac 120atcatcatgc cttcggtgtt cggcaccatc tgcctcctgg gcatcatcgg gaactccacg 180gtcatcttcg cggtcgtgaa gaagtccaag ctgcactggt gcaacaacgt ccccgacatc 240ttcatcatca acctctcggt agtagatctc ctctttctcc tgggcatgcc cttcatgatc 300caccagctca tgggcaatgg ggtgtggcac tttggggaga ccatgtgcac cctcatcacg 360gccatggatg ccaatagtca gttcaccagc acctacatcc tgaccgccat ggccattgac 420cgctacctgg ccactgtcca ccccatctct tccacgaagt tccggaagcc ctctgtggcc 480accctggtga tctgcctcct gtgggccctc tccttcatca gcatcacccc tgtgtggctg 540tatgccagac tcatcccctt cccaggaggt gcagtgggct gcggcatacg cctgcccaac 600ccagacactg acctctactg gttcaccctg taccagtttt tcctggcctt tgccctgcct 660tttgtggtca tcacagccgc atacgtgagg atcctgcagc gcatgacgtc ctcagtggcc 720cccgcctccc agcgcagcat ccggctgcgg acaaagaggg tgacccgcac agccatcgcc 780atctgtctgg tcttctttgt gtgctgggca ctctactatg tgctacagct gacccagttg 840tccatcagcc gcccgaccct cacctttgtc tacttataca atgcggccat cagcttgggc 900tatgccaaca gctgcctcaa cccctttgtg tacatcgtgc tctgtgagac gttccgcaaa 960cgcttggtcc tgtcggtgaa gcctgcagcc caggggcagc ttcgcgctgt cagcaacgct 1020cagacggctg acgaggagag gacagaaagc aaaggcacct ga 1062<210>367<211>353<212>PRT<213>智人(Homo sapiens)<400>367Met Asp Leu Glu Ala Ser Leu Leu Pro Thr Gly Pro Asn Ala Ser Asn1 5 10 15Thr Ser Asp Gly Pro Asp Asn Leu Thr Ser Ala Gly Ser Pro Pro Arg
20 25 30Thr Gly Ser Ile Ser Tyr Ile Asn Ile Ile Met Pro Ser Val Phe Gly
35 40 45Thr Ile Cys Leu Leu Gly Ile Ile Gly Asn Ser Thr Val Ile Phe Ala
50 55 60Val Val Lys Lys Ser Lys Leu His Trp Cys Asn Asn Val Pro Asp Ile65 70 75 80Phe Ile Ile Asn Leu Ser Val Val Asp Leu Leu Phe Leu Leu Gly Met
85 90 95Pro Phe Met Ile His Gln Leu Met Gly Asn Gly Val Trp His Phe Gly
100 105 110Glu Thr Met Cys Thr Leu Ile Thr Ala Met Asp Ala Asn Ser Gln Phe
115 120 125Thr Ser Thr Tyr Ile Leu Thr Ala Met Ala Ile Asp Arg Tyr Leu Ala
130 135 140Thr Val His Pro Ile Ser Ser Thr Lys Phe Arg Lys Pro Ser Val Ala145 150 155 160Thr Leu Val Ile Cys Leu Leu Trp Ala Leu Ser Phe Ile Ser Ile Thr
165 170 175Pro Val Trp Leu Tyr Ala Arg Leu Ile Pro Phe Pro Gly Gly Ala Val
180 185 190Gly Cys Gly Ile Arg Leu Pro Asn Pro Asp Thr Asp Leu Tyr Trp Phe
195 200 205Thr Leu Tyr Gln Phe Phe Leu Ala Phe Ala Leu Pro Phe Val Val Ile
210 215 220Thr Ala Ala Tyr Val Arg Ile Leu Gln Arg Met Thr Ser Ser Val Ala225 230 235 240Pro Ala Ser Gln Arg Ser Ile Arg Leu Arg Thr Lys Arg Val Thr Arg
245 250 255Thr Ala Ile Ala Ile Cys Leu Val Phe Phe Val Cys Trp Ala Leu Tyr
260 265 270Tyr Val Leu Gln Leu Thr Gln Leu Ser Ile Ser Arg Pro Thr Leu Thr
275 280 285Phe Val Tyr Leu Tyr Asn Ala Ala Ile Ser Leu Gly Tyr Ala Asn Ser
290 295 300Cys Leu Asn Pro Phe Val Tyr Ile Val Leu Cys Glu Thr Phe Arg Lys305 310 315 320Arg Leu Val Leu Ser Val Lys Pro Ala Ala Gln Gly Gln Leu Arg Ala
325 330 335Val Ser Asn Ala Gln Thr Ala Asp Glu Glu Arg Thr Glu Ser Lys Gly
340 345 350Thr<210>368<211>34<212>DNA<213>智人(Homo sapiens)<400>368ggtcttcttt gtgtgctgcg caccctacta tgtg 34<210>369<211>34<212>DNA<213>智人(Homo sapiens)<400>369cacatagtag ggtgcgcagc acacaaagaa gacc 34<210>370<211>1062<212>DNA<213>智人(Homo sapiens)<400>370atggacctgg aagcctcgct gctgcccact ggtcccaatg ccagcaacac ctctgatggc 60cccgataacc tcacttcggc aggatcacct cctcgcacgg ggagcatctc ctacatcaac 120atcatcatgc cttcggtgtt cggcaccatc tgcctcctgg gcatcatcgg gaactccacg 180gtcatcttcg cggtcgtgaa gaagtccaag ctgcactggt gcaacaacgt ccccgacatc 240ttcatcatca acctctcggt agtagatctc ctctttctcc tgggcatgcc cttcatgatc 300caccagctca tgggcaatgg ggtgtggcac tttggggaga ccatgtgcac cctcatcacg 360gccatggatg ccaatagtca gttcaccagc acctacatcc tgaccgccat ggccattgac 420cgctacctgg ccactgtcca ccccatctct tccacgaagt tccggaagcc ctctgtggcc 480accctggtga tctgcctcct gtgggccctc tccttcatca gcatcacccc tgtgtggctg 540tatgccagac tcatcccctt cccaggaggt gcagtgggct gcggcatacg cctgcccaac 600ccagacactg acctctactg gttcaccctg taccagtttt tcctggcctt tgccctgcct 660tttgtggtca tcacagccgc atacgtgagg atcctgcagc gcatgacgtc ctcagtggcc 720cccgcctccc agcgcagcat ccggctgcgg acaaagaggg tgacccgcac agccatcgcc 780atctgtctgg tcttctttgt gtgctgcgca ccctactatg tgctacagct gacccagttg 840tccatcagcc gcccgaccct cacctttgtc tacttataca atgcggccat cagcttgggc 900tatgccaaca gctgcctcaa cccctttgtg tacatcgtgc tctgtgagac gttccgcaaa 960cgcttggtcc tgtcggtgaa gcctgcagcc caggggcagc ttcgcgctgt cagcaacgct 1020cagacggctg acgaggagag gacagaaagc aaaggcacct ga 1062<210>371<211>353<212>PRT<213>智人(Homo sapiens)<400>371Met Asp Leu Glu Ala Ser Leu Leu Pro Thr Gly Pro Asn Ala Ser Asn1 5 10 15Thr Ser Asp Gly Pro Asp Asn Leu Thr Ser Ala Gly Ser Pro Pro Arg
20 25 30Thr Gly Ser Ile Ser Tyr Ile Asn Ile Ile Met Pro Ser Val Phe Gly
35 40 45Thr Ile Cys Leu Leu Gly Ile Ile Gly Asn Ser Thr Val Ile Phe Ala
50 55 60Val Val Lys Lys Ser Lys Leu His Trp Cys Asn Asn Val Pro Asp Ile65 70 75 80Phe Ile Ile Asn Leu Ser Val Val Asp Leu Leu Phe Leu Leu Gly Met
85 90 95Pro Phe Met Ile His Gln Leu Met Gly Asn Gly Val Trp His Phe Gly
100 105 110Glu Thr Met Cys Thr Leu Ile Thr Ala Met Asp Ala Asn Ser Gln Phe
115 120 125Thr Ser Thr Tyr Ile Leu Thr Ala Met Ala Ile Asp Arg Tyr Leu Ala
130 135 140Thr Val His Pro Ile Ser Ser Thr Lys Phe Arg Lys Pro Ser Val Ala145 150 155 160Thr Leu Val Ile Cys Leu Leu Trp Ala Leu Ser Phe Ile Ser Ile Thr
165 170 175Pro Val Trp Leu Tyr Ala Arg Leu Ile Pro Phe Pro Gly Gly Ala Val
180 185 190Gly Cys Gly Ile Arg Leu Pro Asn Pro Asp Thr Asp Leu Tyr Trp Phe
195 200 205Thr Leu Tyr Gln Phe Phe Leu Ala Phe Ala Leu Pro Phe Val Val Ile
210 215 220Thr Ala Ala Tyr Val Arg Ile Leu Gln Arg Met Thr Ser Ser Val Ala225 230 235 240Pro Ala Ser Gln Arg Ser Ile Arg Leu Arg Thr Lys Arg Val Thr Arg
245 250 255Thr Ala Ile Ala Ile Cys Leu Val Phe Phe Val Cys Cys Ala Pro Tyr
260 265 270Tyr Val Leu Gln Leu Thr Gln Leu Ser Ile Ser Arg Pro Thr Leu Thr
275 280 285Phe Val Tyr Leu Tyr Asn Ala Ala Ile Ser Leu Gly Tyr Ala Asn Ser
290 295 300Cys Leu Asn Pro Phe Val Tyr Ile Val Leu Cys Glu Thr Phe Arg Lys305 310 315 320Arg Leu Val Leu Ser Val Lys Pro Ala Ala Gln Gly Gln Leu Arg Ala
325 330 335Val Ser Asn Ala Gln Thr Ala Asp Glu Glu Arg Thr Glu Ser Lys Gly
340 345 350Thr<210>372<211>34<212>DNA<213>智人(Homo sapiens)<400>372ggtcttcttt gtgtgcttcg caccctacta tgtg 34<210>373<211>34<212>DNA<213>智人(Homo sapiens)<400>373cacatagtag ggtgcgaagc acacaaagaa gacc 34<210>374<211>1062<212>DNA<213>智人(Homo sapiens)<400>374atggacctgg aagcctcgct gctgcccact ggtcccaatg ccagcaacac ctctgatggc 60cccgataacc tcacttcggc aggatcacct cctcgcacgg ggagcatctc ctacatcaac 120atcatcatgc cttcggtgtt cggcaccatc tgcctcctgg gcatcatcgg gaactccacg 180gtcatcttcg cggtcgtgaa gaagtccaag ctgcactggt gcaacaacgt ccccgacatc 240ttcatcatca acctctcggt agtagatctc ctctttctcc tgggcatgcc cttcatgatc 300caccagctca tgggcaatgg ggtgtggcac tttggggaga ccatgtgcac cctcatcacg 360gccatggatg ccaatagtca gttcaccagc acctacatcc tgaccgccat ggccattgac 420cgctacctgg ccactgtcca ccccatctct tccacgaagt tccggaagcc ctctgtggcc 480accctggtga tctgcctcct gtgggccctc tccttcatca gcatcacccc tgtgtggctg 540tatgccagac tcatcccctt cccaggaggt gcagtgggct gcggcatacg cctgcccaac 600ccagacactg acctctactg gttcaccctg taccagtttt tcctggcctt tgccctgcct 660tttgtggtca tcacagccgc atacgtgagg atcctgcagc gcatgacgtc ctcagtggcc 720cccgcctccc agcgcagcat ccggctgcgg acaaagaggg tgacccgcac agccatcgcc 780atctgtctgg tcttctttgt gtgcttcgca ccctactatg tgctacagct gacccagttg 840tccatcagcc gcccgaccct cacctttgtc tacttataca atgcggccat cagcttgggc 900tatgccaaca gctgcctcaa cccctttgtg tacatcgtgc tctgtgagac gttccgcaaa 960cgcttggtcc tgtcggtgaa gcctgcagcc caggggcagc ttcgcgctgt cagcaacgct 1020cagacggctg acgaggagag gacagaaagc aaaggcacct ga 1062<210>375<211>353<212>PRT<213>智人(Homo sapiens)<400>375Met Asp Leu Glu Ala Ser Leu Leu Pro Thr Gly Pro Asn Ala Ser Asn1 5 10 15Thr Ser Asp Gly Pro Asp Asn Leu Thr Ser Ala Gly Ser Pro Pro Arg
20 25 30Thr Gly Ser Ile Ser Tyr Ile Asn Ile Ile Met Pro Ser Val Phe Gly
35 40 45Thr Ile Cys Leu Leu Gly Ile Ile Gly Asn Ser Thr Val Ile Phe Ala
50 55 60Val Val Lys Lys Ser Lys Leu His Trp Cys Asn Asn Val Pro Asp Ile65 70 75 80Phe Ile Ile Asn Leu Ser Val Val Asp Leu Leu Phe Leu Leu Gly Met
85 90 95Pro Phe Met Ile His Gln Leu Met Gly Asn Gly Val Trp His Phe Gly
100 105 110Glu Thr Met Cys Thr Leu Ile Thr Ala Met Asp Ala Asn Ser Gln Phe
115 120 125Thr Ser Thr Tyr Ile Leu Thr Ala Met Ala Ile Asp Arg Tyr Leu Ala
130 135 140Thr Val His Pro Ile Ser Ser Thr Lys Phe Arg Lys Pro Ser Val Ala145 150 155 160Thr Leu Val Ile Cys Leu Leu Trp Ala Leu Ser Phe Ile Ser Ile Thr
165 170 175Pro Val Trp Leu Tyr Ala Arg Leu Ile Pro Phe Pro Gly Gly Ala Val
180 185 190Gly Cys Gly Ile Arg Leu Pro Asn Pro Asp Thr Asp Leu Tyr Trp Phe
195 200 205Thr Leu Tyr Gln Phe Phe Leu Ala Phe Ala Leu Pro Phe Val Val Ile
210 215 220Thr Ala Ala Tyr Val Arg Ile Leu Gln Arg Met Thr Ser Ser Val Ala225 230 235 240Pro Ala Ser Gln Arg Ser Ile Arg Leu Arg Thr Lys Arg Val Thr Arg
245 250 255Thr Ala Ile Ala Ile Cys Leu Val Phe Phe Val Cys Phe Ala Pro Tyr
260 265 270Tyr Val Leu Gln Leu Thr Gln Leu Ser Ile Ser Arg Pro Thr Leu Thr
275 280 285Phe Val Tyr Leu Tyr Asn Ala Ala Ile Ser Leu Gly Tyr Ala Asn Ser
290 295 300Cys Leu Asn Pro Phe Val Tyr Ile Val Leu Cys Glu Thr Phe Arg Lys305 310 315 320Arg Leu Val Leu Ser Val Lys Pro Ala Ala Gln Gly Gln Leu Arg Ala
325 330 335Val Ser Asn Ala Gln Thr Ala Asp Glu Glu Arg Thr Glu Ser Lys Gly
340 345 350Thr<210>376<211>34<212>DNA<213>智人(Homo sapiens)<400>376ggtcttcttt gtgtgcttgg caccctacta tgtg 34<210>377<211>34<212>DNA<213>智人(Homo sapiens)<400>377cacatagtag ggtgccaagc acacaaagaa gacc 34<210>378<211>1062<212>DNA<213>智人(Homo sapiens)<400>378atggacctgg aagcctcgct gctgcccact ggtcccaatg ccagcaacac ctctgatggc 60cccgataacc tcacttcggc aggatcacct cctcgcacgg ggagcatctc ctacatcaac 120atcatcatgc cttcggtgtt cggcaccatc tgcctcctgg gcatcatcgg gaactccacg 180gtcatcttcg cggtcgtgaa gaagtccaag ctgcactggt gcaacaacgt ccccgacatc 240ttcatcatca acctctcggt agtagatctc ctctttctcc tgggcatgcc cttcatgatc 300caccagctca tgggcaatgg ggtgtggcac tttggggaga ccatgtgcac cctcatcacg 360gccatggatg ccaatagtca gttcaccagc acctacatcc tgaccgccat ggccattgac 420cgctacctgg ccactgtcca ccccatctct tccacgaagt tccggaagcc ctctgtggcc 480accctggtga tctgcctcct gtgggccctc tccttcatca gcatcacccc tgtgtggctg 540tatgccagac tcatcccctt cccaggaggt gcagtgggct gcggcatacg cctgcccaac 600ccagacactg acctctactg gttcaccctg taccagtttt tcctggcctt tgccctgcct 660tttgtggtca tcacagccgc atacgtgagg atcctgcagc gcatgacgtc ctcagtggcc 720cccgcctccc agcgcagcat ccggctgcgg acaaagaggg tgacccgcac agccatcgcc 780atctgtctgg tcttctttgt gtgcttggca ccctactatg tgctacagct gacccagttg 840tccatcagcc gcccgaccct cacctttgtc tacttataca atgcggccat cagcttgggc 900tatgccaaca gctgcctcaa cccctttgtg tacatcgtgc tctgtgagac gttccgcaaa 960cgcttggtcc tgtcggtgaa gcctgcagcc caggggcagc ttcgcgctgt cagcaacgct 1020cagacggctg acgaggagag gacagaaagc aaaggcacct ga 1062<210>379<211>353<212>PRT<213>智人(Homo sapiens)<400>379Met Asp Leu Glu Ala Ser Leu Leu Pro Thr Gly Pro Asn Ala Ser Asn1 5 10 15Thr Ser Asp Gly Pro Asp Asn Leu Thr Ser Ala Gly Ser Pro Pro Arg
20 25 30Thr Gly Ser Ile Ser Tyr Ile Asn Ile Ile Met Pro Ser Val Phe Gly
35 40 45Thr Ile Cys Leu Leu Gly Ile Ile Gly Asn Ser Thr Val Ile Phe Ala
50 55 60Val Val Lys Lys Ser Lys Leu His Trp Cys Asn Asn Val Pro Asp Ile65 70 75 80Phe Ile Ile Asn Leu Ser Val Val Asp Leu Leu Phe Leu Leu Gly Met
85 90 95Pro Phe Met Ile His Gln Leu Met Gly Asn Gly Val Trp His Phe Gly
100 105 110Glu Thr Met Cys Thr Leu Ile Thr Ala Met Asp Ala Asn Ser Gln Phe
115 120 125Thr Ser Thr Tyr Ile Leu Thr Ala Met Ala Ile Asp Arg Tyr Leu Ala
130 135 140Thr Val His Pro Ile Ser Ser Thr Lys Phe Arg Lys Pro Ser Val Ala145 150 155 160Thr Leu Val Ile Cys Leu Leu Trp Ala Leu Ser Phe Ile Ser Ile Thr
165 170 175Pro Val Trp Leu Tyr Ala Arg Leu Ile Pro Phe Pro Gly Gly Ala Val
180 185 190Gly Cys Gly Ile Arg Leu Pro Asn Pro Asp Thr Asp Leu Tyr Trp Phe
195 200 205Thr Leu Tyr Gln Phe Phe Leu Ala Phe Ala Leu Pro Phe Val Val Ile
210 215 220Thr Ala Ala Tyr Val Arg Ile Leu Gln Arg Met Thr Ser Ser Val Ala225 230 235 240Pro Ala Ser Gln Arg Ser Ile Arg Leu Arg Thr Lys Arg Val Thr Arg
245 250 255Thr Ala Ile Ala Ile Cys Leu Val Phe Phe Val Cys Leu Ala Pro Tyr
260 265 270Tyr Val Leu Gln Leu Thr Gln Leu Ser Ile Ser Arg Pro Thr Leu Thr
275 280 285Phe Val Tyr Leu Tyr Asn Ala Ala Ile Ser Leu Gly Tyr Ala Asn Ser
290 295 300Cys Leu Asn Pro Phe Val Tyr Ile Val Leu Cys Glu Thr Phe Arg Lys305 310 315 320Arg Leu Val Leu Ser Val Lys Pro Ala Ala Gln Gly Gln Leu Arg Ala
325 330 335Val Ser Asn Ala Gln Thr Ala Asp Glu Glu Arg Thr Glu Ser Lys Gly
340 345 350Thr<210>380<211>31<212>DNA<213>智人(Homo sapiens)<400>380gccatctgtc tggtcatctt tgtgtgctgg g 31<210>381<211>31<212>DNA<213>智人(Homo sapiens)<400>381cccagcacac aaagatgacc agacagatgg c 31<210>382<211>1062<212>DNA<213>智人(Homo sapiens)<400>382atggacctgg aagcctcgct gctgcccact ggtcccaatg ccagcaacac ctctgatggc 60cccgataacc tcacttcggc aggatcacct cctcgcacgg ggagcatctc ctacatcaac 120atcatcatgc cttcggtgtt cggcaccatc tgcctcctgg gcatcatcgg gaactccacg 180gtcatcttcg cggtcgtgaa gaagtccaag ctgcactggt gcaacaacgt ccccgacatc 240ttcatcatca acctctcggt agtagatctc ctctttctcc tgggcatgcc cttcatgatc 300caccagctca tgggcaatgg ggtgtggcac tttggggaga ccatgtgcac cctcatcacg 360gccatggatg ccaatagtca gttcaccagc acctacatcc tgaccgccat ggccattgac 420cgctacctgg ccactgtcca ccccatctct tccacgaagt tccggaagcc ctctgtggcc 480accctggtga tctgcctcct gtgggccctc tccttcatca gcatcacccc tgtgtggctg 540tatgccagac tcatcccctt cccaggaggt gcagtgggct gcggcatacg cctgcccaac 600ccagacactg acctctactg gttcaccctg taccagtttt tcctggcctt tgccctgcct 660tttgtggtca tcacagccgc atacgtgagg atcctgcagc gcatgacgtc ctcagtggcc 720cccgcctccc agcgcagcat ccggctgcgg acaaagaggg tgacccgcac agccatcgcc 780atctgtctgg tcatctttgt gtgctgggca ccctactatg tgctacagct gacccagttg 840tccatcagcc gcccgaccct cacctttgtc tacttataca atgcggccat cagcttgggc 900tatgccaaca gctgcctcaa cccctttgtg tacatcgtgc tctgtgagac gttccgcaaa 960cgcttggtcc tgtcggtgaa gcctgcagcc caggggcagc ttcgcgctgt cagcaacgct 1020cagacggctg acgaggagag gacagaaagc aaaggcacct ga 1062<210>383<211>353<212>PRT<213>智人(Homo sapiens)<400>383Met Asp Leu Glu Ala Ser Leu Leu Pro Thr Gly Pro Asn Ala Ser Asn1 5 10 15Thr Ser Asp Gly Pro Asp Asn Leu Thr Ser Ala Gly Ser Pro Pro Arg
20 25 30Thr Gly Ser Ile Ser Tyr Ile Asn Ile Ile Met Pro Ser Val Phe Gly
35 40 45Thr Ile Cys Leu Leu Gly Ile Ile Gly Asn Ser Thr Val Ile Phe Ala
50 55 60Val Val Lys Lys Ser Lys Leu His Trp Cys Asn Asn Val Pro Asp Ile65 70 75 80Phe Ile Ile Asn Leu Ser Val Val Asp Leu Leu Phe Leu Leu Gly Met
85 90 95Pro Phe Met Ile His Gln Leu Met Gly Asn Gly Val Trp His Phe Gly
100 105 110Glu Thr Met Cys Thr Leu Ile Thr Ala Met Asp Ala Asn Ser Gln Phe
115 120 125Thr Ser Thr Tyr Ile Leu Thr Ala Met Ala Ile Asp Arg Tyr Leu Ala
130 135 140Thr Val His Pro Ile Ser Ser Thr Lys Phe Arg Lys Pro Ser Val Ala145 150 155 160Thr Leu Val Ile Cys Leu Leu Trp Ala Leu Ser Phe Ile Ser Ile Thr
165 170 175Pro Val Trp Leu Tyr Ala Arg Leu Ile Pro Phe Pro Gly Gly Ala Val
180 185 190Gly Cys Gly Ile Arg Leu Pro Asn Pro Asp Thr Asp Leu Tyr Trp Phe
195 200 205Thr Leu Tyr Gln Phe Phe Leu Ala Phe Ala Leu Pro Phe Val Val Ile
210 215 220Thr Ala Ala Tyr Val Arg Ile Leu Gln Arg Met Thr Ser Ser Val Ala225 230 235 240Pro Ala Ser Gln Arg Ser Ile Arg Leu Arg Thr Lys Arg Val Thr Arg
245 250 255Thr Ala Ile Ala Ile Cys Leu Val Ile Phe Val Cys Trp Ala Pro Tyr
260 265 270Tyr Val Leu Gln Leu Thr Gln Leu Ser Ile Ser Arg Pro Thr Leu Thr
275 280 285Phe Val Tyr Leu Tyr Asn Ala Ala Ile Ser Leu Gly Tyr Ala Asn Ser
290 295 300Cys Leu Asn Pro Phe Val Tyr Ile Val Leu Cys Glu Thr Phe Arg Lys305 310 315 320Arg Leu Val Leu Ser Val Lys Pro Ala Ala Gln Gly Gln Leu Arg Ala
325 330 335Val Ser Asn Ala Gln Thr Ala Asp Glu Glu Arg Thr Glu Ser Lys Gly
340 345 350Thr<210>384<211>36<212>DNA<213>智人(Homo sapiens)<400>384cgcacagcca tcgcccagtg tctggtcttc tttgtg 36<210>385<211>36<212>DNA<213>智人(Homo sapiens)<400>385cacaaagaag accagacact gggcgatggc tgtgcg 36<210>386<211>1062<212>DNA<213>智人(Homo sapiens)<400>386atggacctgg aagcctcgct gctgcccact ggtcccaatg ccagcaacac ctctgatggc 60cccgataacc tcacttcggc aggatcacct cctcgcacgg ggagcatctc ctacatcaac 120atcatcatgc cttcggtgtt cggcaccatc tgcctcctgg gcatcatcgg gaactccacg 180gtcatcttcg cggtcgtgaa gaagtccaag ctgcactggt gcaacaacgt ccccgacatc 240ttcatcatca acctctcggt agtagatctc ctctttctcc tgggcatgcc cttcatgatc 300caccagctca tgggcaatgg ggtgtggcac tttggggaga ccatgtgcac cctcatcacg 360gccatggatg ccaatagtca gttcaccagc acctacatcc tgaccgccat ggccattgac 420cgctacctgg ccactgtcca ccccatctct tccacgaagt tccggaagcc ctctgtggcc 480accctggtga tctgcctcct gtgggccctc tccttcatca gcatcacccc tgtgtggctg 540tatgccagac tcatcccctt cccaggaggt gcagtgggct gcggcatacg cctgcccaac 600ccagacactg acctctactg gttcaccctg taccagtttt tcctggcctt tgccctgcct 660tttgtggtca tcacagccgc atacgtgagg atcctgcagc gcatgacgtc ctcagtggcc 720cccgcctccc agcgcagcat ccggctgcgg acaaagaggg tgacccgcac agccatcgcc 780cagtgtctgg tcttctttgt gtgctgggca ccctactatg tgctacagct gacccagttg 840tccatcagcc gcccgaccct cacctttgtc tacttataca atgcggccat cagcttgggc 900tatgccaaca gctgcctcaa cccctttgtg tacatcgtgc tctgtgagac gttccgcaaa 960cgcttggtcc tgtcggtgaa gcctgcagcc caggggcagc ttcgcgctgt cagcaacgct 1020cagacggctg acgaggagag gacagaaagc aaaggcacct ga 1062<210>387<211>353<212>PRT<213>智人(Homo sapiens)<400>387Met Asp Leu Glu Ala Ser Leu Leu Pro Thr Gly Pro Asn Ala Ser Asn1 5 10 15Thr Ser Asp Gly Pro Asp Asn Leu Thr Ser Ala Gly Ser Pro Pro Arg
20 25 30Thr Gly Ser Ile Ser Tyr Ile Asn Ile Ile Met Pro Ser Val Phe Gly
35 40 45Thr Ile Cys Leu Leu Gly Ile Ile Gly Asn Ser Thr Val Ile Phe Ala
50 55 60Val Val Lys Lys Ser Lys Leu His Trp Cys Asn Asn Val Pro Asp Ile65 70 75 80Phe Ile Ile Asn Leu Ser Val Val Asp Leu Leu Phe Leu Leu Gly Met
85 90 95Pro Phe Met Ile His Gln Leu Met Gly Asn Gly Val Trp His Phe Gly
100 105 110Glu Thr Met Cys Thr Leu Ile Thr Ala Met Asp Ala Asn Ser Gln Phe
115 120 125Thr Ser Thr Tyr Ile Leu Thr Ala Met Ala Ile Asp Arg Tyr Leu Ala
130 135 140Thr Val His Pro Ile Ser Ser Thr Lys Phe Arg Lys Pro Ser Val Ala145 150 155 160Thr Leu Val Ile Cys Leu Leu Trp Ala Leu Ser Phe Ile Ser Ile Thr
165 170 175Pro Val Trp Leu Tyr Ala Arg Leu Ile Pro Phe Pro Gly Gly Ala Val
180 185 190Gly Cys Gly Ile Arg Leu Pro Asn Pro Asp Thr Asp Leu Tyr Trp Phe
195 200 205Thr Leu Tyr Gln Phe Phe Leu Ala Phe Ala Leu Pro Phe Val Val Ile
210 215 220Thr Ala Ala Tyr Val Arg Ile Leu Gln Arg Met Thr Ser Ser Val Ala225 230 235 240Pro Ala Ser Gln Arg Ser Ile Arg Leu Arg Thr Lys Arg Val Thr Arg
245 250 255Thr Ala Ile Ala Gln Cys Leu Val Phe Phe Val Cys Trp Ala Pro Tyr
260 265 270Tyr Val Leu Gln Leu Thr Gln Leu Ser Ile Ser Arg Pro Thr Leu Thr
275 280 285Phe Val Tyr Leu Tyr Asn Ala Ala Ile Ser Leu Gly Tyr Ala Asn Ser
290 295 300Cys Leu Asn Pro Phe Val Tyr Ile Val Leu Cys Glu Thr Phe Arg Lys305 310 315 320Arg Leu Val Leu Ser Val Lys Pro Ala Ala Gln Gly Gln Leu Arg Ala
325 330 335Val Ser Asn Ala Gln Thr Ala Asp Glu Glu Arg Thr Glu Ser Lys Gly
340 345 350Thr<210>388<211>33<212>DNA<213>智人(Homo sapiens)<400>388accgccatgg ccattaacgc gtacctggcc act 33<210>389<211>33<212>DNA<213>智人(Homo sapiens)<400>389agtggccagg tagcggttaa tggccatggc ggt 33<210>390<211>1062<212>DNA<213>智人(Homo sapiens)<400>390atggacctgg aagcctcgct gctgcccact ggtcccaatg ccagcaacac ctctgatggc 60cccgataacc tcacttcggc aggatcacct cctcgcacgg ggagcatctc ctacatcaac 120atcatcatgc cttcggtgtt cggcaccatc tgcctcctgg gcatcatcgg gaactccacg 180gtcatcttcg cggtcgtgaa gaagtccaag ctgcactggt gcaacaacgt ccccgacatc 240ttcatcatca acctctcggt agtagatctc ctctttctcc tgggcatgcc cttcatgatc 300caccagctca tgggcaatgg ggtgtggcac tttggggaga ccatgtgcac cctcatcacg 360gccatggatg ccaatagtca gttcaccagc acctacatcc tgaccgccat ggccattaac 420cgctacctgg ccactgtcca ccccatctct tccacgaagt tccggaagcc ctctgtggcc 480accctggtga tctgcctcct gtgggccctc tccttcatca gcatcacccc tgtgtggctg 540tatgccagac tcatcccctt cccaggaggt gcagtgggct gcggcatacg cctgcccaac 600ccagacactg acctctactg gttcaccctg taccagtttt tcctggcctt tgccctgcct 660tttgtggtca tcacagccgc atacgtgagg atcctgcagc gcatgacgtc ctcagtggcc 720cccgcctccc agcgcagcat ccggctgcgg acaaagaggg tgacccgcac agccatcgcc 780atctgtctgg tcttctttgt gtgctgggca ccctactatg tgctacagct gacccagttg 840tccatcagcc gcccgaccct cacctttgtc tacttataca atgcggccat cagcttgggc 900tatgccaaca gctgcctcaa cccctttgtg tacatcgtgc tctgtgagac gttccgcaaa 960cgcttggtcc tgtcggtgaa gcctgcagcc caggggcagc ttcgcgctgt cagcaacgct 1020cagacggctg acgaggagag gacagaaagc aaaggcacct ga 1062<210>391<211>353<212>PRT<213>智人(Homo sapiens)<400>391Met Asp Leu Glu Ala Ser Leu Leu Pro Thr Gly Pro Asn Ala Ser Asn1 5 10 15Thr Ser Asp Gly Pro Asp Asn Leu Thr Ser Ala Gly Ser Pro Pro Arg
20 25 30Thr Gly Ser Ile Ser Tyr Ile Asn Ile Ile Met Pro Ser Val Phe Gly
35 40 45Thr Ile Cys Leu Leu Gly Ile Ile Gly Asn Ser Thr Val Ile Phe Ala
50 55 60Val Val Lys Lys Ser Lys Leu His Trp Cys Asn Asn Val Pro Asp Ile65 70 75 80Phe Ile Ile Asn Leu Ser Val Val Asp Leu Leu Phe Leu Leu Gly Met
85 90 95Pro Phe Met Ile His Gln Leu Met Gly Asn Gly Val Trp His Phe Gly
100 105 110Glu Thr Met Cys Thr Leu Ile Thr Ala Met Asp Ala Asn Ser Gln Phe
115 120 125Thr Ser Thr Tyr Ile Leu Thr Ala Met Ala Ile Asn Arg Tyr Leu Ala
130 135 140Thr Val His Pro Ile Ser Ser Thr Lys Phe Arg Lys Pro Ser Val Ala145 150 155 160Thr Leu Val Ile Cys Leu Leu Trp Ala Leu Ser Phe Ile Ser Ile Thr
165 170 175Pro Val Trp Leu Tyr Ala Arg Leu Ile Pro Phe Pro Gly Gly Ala Val
180 185 190Gly Cys Gly Ile Arg Leu Pro Asn Pro Asp Thr Asp Leu Tyr Trp Phe
195 200 205Thr Leu Tyr Gln Phe Phe Leu Ala Phe Ala Leu Pro Phe Val Val Ile
210 215 220Thr Ala Ala Tyr Val Arg Ile Leu Gln Arg Met Thr Ser Ser Val Ala225 230 235 240Pro Ala Ser Gln Arg Ser Ile Arg Leu Arg Thr Lys Arg Val Thr Arg
245 250 255Thr Ala Ile Ala Ile Cys Leu Val Phe Phe Val Cys Trp Ala Pro Tyr
260 265 270Tyr Val Leu Gln Leu Thr Gln Leu Ser Ile Ser Arg Pro Thr Leu Thr
275 280 285Phe Val Tyr Leu Tyr Asn Ala Ala Ile Ser Leu Gly Tyr Ala Asn Ser
290 295 300Cys Leu Asn Pro Phe Val Tyr Ile Val Leu Cys Glu Thr Phe Arg Lys305 310 315 320Arg Leu Val Leu Ser Val Lys Pro Ala Ala Gln Gly Gln Leu Arg Ala
325 330 335Val Ser Asn Ala Gln Thr Ala Asp Glu Glu Arg Thr Glu Ser Lys Gly
340 345 350Thr<210>392<211>32<212>DNA<213>智人(Homo sapiens)<400>392caagcgagtt atcggcatat acgctgacgg tc 32<210>393<211>32<212>DNA<213>智人(Homo sapiens)<400>393gaccgtcagc gtatatgccg ataactcgct tg 32<210>394<211>2292<212>DNA<213>智人(Homo sapiens)<400>394atgaggccgg cggacttgct gcagctggtg ctgctgctcg acctgcccag ggacctgggc 60ggaatggggt gttcgtctcc accctgcgag tgccatcagg aggaggactt cagagtcacc 120tgcaaggata ttcaacgcat ccccagctta ccgcccagta cgcagactct gaagcttatt 180gagactcacc tgagaactat tccaagtcat gcattttcta atctgcccaa tatttccaga 240atctacgtat ctatagatgt gactctgcag cagctggaat cacactcctt ctacaatttg 300agtaaagtga ctcacataga aattcggaat accaggaact taacttacat agaccctgat 360gccctcaaag agctccccct cctaaagttc cttggcattt tcaacactgg acttaaaatg 420ttccctgacc tgaccaaagt ttattccact gatatattct ttatacttga aattacagac 480aacccttaca tgacgtcaat ccctgtgaat gcttttcagg gactatgcaa tgaaaccttg 540acactgaagc tgtacaacaa cggctttact tcagtccaag gatatgcttt caatgggaca 600aagctggatg ctgtttacct aaacaagaat aaatacctga cagttattga caaagatgca 660tttggaggag tatacagtgg accaagcttg ctggacgtgt ctcaaaccag tgtcactgcc 720cttccatcca aaggcctgga gcacctgaag gaactgatag caagaaacac ctggactctt 780aagaaacttc cactttcctt gagtttcctt cacctcacac gggctgacct ttcttaccca 840agccactgct gtgcctttaa gaatcagaag aaaatcagag gaatccttga gtccttgatg 900tgtaatgaga gcagtatgca gagcttgcgc cagagaaaat ctgtgaatgc cttgaatagc 960cccctccacc aggaatatga agagaatctg ggtgacagca ttgttgggta caaggaaaag 1020tccaagttcc aggatactca taacaacgct cattattacg tcttctttga agaacaagag 1080gatgagatca ttggttttgg ccaggagctc aaaaaccccc aggaagagac tctacaagct 1140tttgacagcc attatgacta caccatatgt ggggacagtg aagacatggt gtgtaccccc 1200aagtccgatg agttcaaccc gtgtgaagac ataatgggct acaagttcct gagaattgtg 1260gtgtggttcg ttagtctgct ggctctcctg ggcaatgtct ttgtcctgct tattctcctc 1320accagccact acaaactgaa cgtcccccgc tttctcatgt gcaacctggc ctttgcggat 1380ttctgcatgg ggatgtacct gctcctcatc gcctctgtag acctctacac tcactctgag 1440tactacaacc atgccatcga ctggcagaca ggccctgggt gcaacacggc tggtttcttc 1500actgtctttg caagcgagtt atcggtgcat acgctgacgg tcatcaccct ggagcgctgg 1560tatgccatca ccttcgccat gcgcctggac cggaagatcc gcctcaggca cgcatgtgcc 1620atcatggttg ggggctgggt ttgctgcttc cttctcgccc tgcttccttt ggtgggaata 1680agtagctatg ccaaagtcag tatctgcctg cccatggaca ccgagacccc tcttgctctg 1740gcatatattg tttttgttct gacgctcaac atagttgcct tcgtcatcgt ctgctgctgt 1800tatgtgaaga tctacatcac agtccgaaat ccgcagtaca acccagggga caaagatacc 1860aaaattgcca agaggatggc tgtgttgatc ttcaccgact tcatatgcat ggccccaatc 1920tcattctatg ctctgtcagc aattctgaac aagcctctca tcactgttag caactccaaa 1980atcttgctgg tactcttcta tccacttaac tcctgtgcca atccattcct ctatgctatt 2040ttcaccaagg ccttccagag ggatgtgttc atcctactca gcaagtttgg catctgtaaa 2100cgccaggctc aggcataccg ggggcagagg gttcctccaa agaacagcac tgatattcag 2160gttcaaaagg ttacccacga gatgaggcag ggtctccaca acatggaaga tgtctatgaa 2220ctgattgaaa agtcccatct aaccccaaag aagcaaggcc aaatctcaga agagtatatg 2280caaacggttt tg 2292<210>395<211>764<212>PRT<213>智人(Homo sapiens)<400>395Met Arg Pro Ala Asp Leu Leu Gln Leu Val Leu Leu Leu Asp Leu Pro1 5 10 15Arg Asp Leu Gly Gly Met Gly Cys Ser Ser Pro Pro Cys Glu Cys His
20 25 30Gln Glu Glu Asp Phe Arg Val Thr Cys Lys Asp Ile Gln Arg Ile Pro
35 40 45Ser Leu Pro Pro Ser Thr Gln Thr Leu Lys Leu Ile Glu Thr His Leu
50 55 60Arg Thr Ile Pro Ser His Ala Phe Ser Asn Leu Pro Asn Ile Ser Arg65 70 75 80Ile Tyr Val Ser Ile Asp Val Thr Leu Gln Gln Leu Glu Ser His Ser
85 90 95Phe Tyr Asn Leu Ser Lys Val Thr His Ile Glu Ile Arg Asn Thr Arg
100 105 110Asn Leu Thr Tyr Ile Asp Pro Asp Ala Leu Lys Glu Leu Pro Leu Leu
115 120 125Lys Phe Leu Gly Ile Phe Asn Thr Gly Leu Lys Met Phe Pro Asp Leu
130 135 140Thr Lys Val Tyr Ser Thr Asp Ile Phe Phe Ile Leu Glu Ile Thr Asp145 150 155 160Asn Pro Tyr Met Thr Ser Ile Pro Val Asn Ala Phe Gln Gly Leu Cys
165 170 175Asn Glu Thr Leu Thr Leu Lys Leu Tyr Asn Asn Gly Phe Thr Ser Val
180 185 190Gln Gly Tyr Ala Phe Asn Gly Thr Lys Leu Asp Ala Val Tyr Leu Asn
195 200 205Lys Asn Lys Tyr Leu Thr Val Ile Asp Lys Asp Ala Phe Gly Gly Val
210 215 220Tyr Ser Gly Pro Ser Leu Leu Asp Val Ser Gln Thr Ser Val Thr Ala225 230 235 240Leu Pro Ser Lys Gly Leu Glu His Leu Lys Glu Leu Ile Ala Arg Asn
245 250 255Thr Trp Thr Leu Lys Lys Leu Pro Leu Ser Leu Ser Phe Leu His Leu
260 265 270Thr Arg Ala Asp Leu Ser Tyr Pro Ser His Cys Cys Ala Phe Lys Asn
275 280 285Gln Lys Lys Ile Arg Gly Ile Leu Glu Ser Leu Met Cys Asn Glu Ser
290 295 300Ser Met Gln Ser Leu Arg Gln Arg Lys Ser Val Asn Ala Leu Asn Ser305 310 315 320Pro Leu His Gln Glu Tyr Glu Glu Asn Leu Gly Asp Ser Ile Val Gly
325 330 335Tyr Lys Glu Lys Ser Lys Phe Gln Asp Thr His Asn Asn Ala His Tyr
340 345 350Tyr Val Phe Phe Glu Glu Gln Glu Asp Glu Ile Ile Gly Phe Gly Gln
355 360 365Glu Leu Lys Asn Pro Gln Glu Glu Thr Leu Gln Ala Phe Asp Ser His
370 375 380Tyr Asp Tyr Thr Ile Cys Gly Asp Ser Glu Asp Met Val Cys Thr Pro385 390 395 400Lys Ser Asp Glu Phe Asn Pro Cys Glu Asp Ile Met Gly Tyr Lys Phe
405 410 415Leu Arg Ile Val Val Trp Phe Val Ser Leu Leu Ala Leu Leu Gly Asn
420 425 430Val Phe Val Leu Leu Ile Leu Leu Thr Ser His Tyr Lys Leu Asn Val
435 440 445Pro Arg Phe Leu Met Cys Asn Leu Ala Phe Ala Asp Phe Cys Met Gly
450 455 460Met Tyr Leu Leu Leu Ile Ala Ser Val Asp Leu Tyr Thr His Ser Glu465 470 475 480Tyr Tyr Asn His Ala Ile Asp Trp Gln Thr Gly Pro Gly Cys Asn Thr
485 490 495Ala Gly Phe Phe Thr Val Phe Ala Ser Glu Leu Ser Ala Tyr Thr Leu
500 505 510Thr Val Ile Thr Leu Glu Arg Trp Tyr Ala Ile Thr Phe Ala Met Arg
515 520 525Leu Asp Arg Lys Ile Arg Leu Arg His Ala Cys Ala Ile Met Val Gly
530 535 540Gly Trp Val Cys Cys Phe Leu Leu Ala Leu Leu Pro Leu Val Gly Ile545 550 555 560Ser Ser Tyr Ala Lys Val Ser Ile Cys Leu Pro Met Asp Thr Glu Thr
565 570 575Pro Leu Ala Leu Ala Tyr Ile Val Phe Val Leu Thr Leu Asn Ile Val
580 585 590Ala Phe Val Ile Val Cys Cys Cys Tyr Val Lys Ile Tyr Ile Thr Val
595 600 605Arg Asn Pro Gln Tyr Asn Pro Gly Asp Lys Asp Thr Lys Ile Ala Lys
610 615 620Arg Met Ala Val Leu Ile Phe Thr Asp Phe Ile Cys Met Ala Pro Ile625 630 635 640Ser Phe Tyr Ala Leu Ser Ala Ile Leu Asn Lys Pro Leu Ile Thr Val
645 650 655Ser Asn Ser Lys Ile Leu Leu Val Leu Phe Tyr Pro Leu Asn Ser Cys
660 665 670Ala Asn Pro Phe Leu Tyr Ala Ile Phe Thr Lys Ala Phe Gln Arg Asp
675 680 685Val Phe Ile Leu Leu Ser Lys Phe Gly Ile Cys Lys Arg Gln Ala Gln
690 695 700Ala Tyr Arg Gly Gln Arg Val Pro Pro Lys Asn Ser Thr Asp Ile Gln705 710 715 720Val Gln Lys Val Thr His Glu Met Arg Gln Gly Leu His Asn Met Glu
725 730 735Asp Val Tyr Glu Leu Ile Glu Lys Ser His Leu Thr Pro Lys Lys Gln
740 745 750Gly Gln Ile Ser Glu Glu Tyr Met Gln Thr Val Leu
755 760<210>396<211>31<212>DNA<213>智人(Homo sapiens)<400>396acccagggga caaaggtacc aaaattgcca a 31<210>397<211>31<212>DNA<213>智人(Homo sapiens)<400>397ttggcaattt tggtaccttt gtcccctggg t 31<210>398<211>2292<212>DNA<213>智人(Homo sapiens)<400>398atgaggccgg cggacttgct gcagctggtg ctgctgctcg acctgcccag ggacctgggc 60ggaatggggt gttcgtctcc accctgcgag tgccatcagg aggaggactt cagagtcacc 120tgcaaggata ttcaacgcat ccccagctta ccgcccagta cgcagactct gaagcttatt 180gagactcacc tgagaactat tccaagtcat gcattttcta atctgcccaa tatttccaga 240atctacgtat ctatagatgt gactctgcag cagctggaat cacactcctt ctacaatttg 300agtaaagtga ctcacataga aattcggaat accaggaact taacttacat agaccctgat 360gccctcaaag agctccccct cctaaagttc cttggcattt tcaacactgg acttaaaatg 420ttccctgacc tgaccaaagt ttattccact gatatattct ttatacttga aattacagac 480aacccttaca tgacgtcaat ccctgtgaat gcttttcagg gactatgcaa tgaaaccttg 540acactgaagc tgtacaacaa cggctttact tcagtccaag gatatgcttt caatgggaca 600aagctggatg ctgtttacct aaacaagaat aaatacctga cagttattga caaagatgca 660tttggaggag tatacagtgg accaagcttg ctggacgtgt ctcaaaccag tgtcactgcc 720cttccatcca aaggcctgga gcacctgaag gaactgatag caagaaacac ctggactctt 780aagaaacttc cactttcctt gagtttcctt cacctcacac gggctgacct ttcttaccca 840agccactgct gtgcctttaa gaatcagaag aaaatcagag gaatccttga gtccttgatg 900tgtaatgaga gcagtatgca gagcttgcgc cagagaaaat ctgtgaatgc cttgaatagc 960cccctccacc aggaatatga agagaatctg ggtgacagca ttgttgggta caaggaaaag 1020tccaagttcc aggatactca taacaacgct cattattacg tcttctttga agaacaagag 1080gatgagatca ttggttttgg ccaggagctc aaaaaccccc aggaagagac tctacaagct 1140tttgacagcc attatgacta caccatatgt ggggacagtg aagacatggt gtgtaccccc 1200aagtccgatg agttcaaccc gtgtgaagac ataatgggct acaagttcct gagaattgtg 1260gtgtggttcg ttagtctgct ggctctcctg ggcaatgtct ttgtcctgct tattctcctc 1320accagccact acaaactgaa cgtcccccgc tttctcatgt gcaacctggc ctttgcggat 1380ttctgcatgg ggatgtacct gctcctcatc gcctctgtag acctctacac tcactctgag 1440tactacaacc atgccatcga ctggcagaca ggccctgggt gcaacacggc tggtttcttc 1500actgtctttg caagcgagtt atcggtgtat acgctgacgg tcatcaccct ggagcgctgg 1560tatgccatca ccttcgccat gcgcctggac cggaagatcc gcctcaggca cgcatgtgcc 1620atcatggttg ggggctgggt ttgctgcttc cttctcgccc tgcttccttt ggtgggaata 1680agtagctatg ccaaagtcag tatctgcctg cccatggaca ccgagacccc tcttgctctg 1740gcatatattg tttttgttct gacgctcaac atagttgcct tcgtcatcgt ctgctgctgt 1800tatgtgaaga tctacatcac agtccgaaat ccgcagtaca acccagggga caaaggtacc 1860aaaattgcca agaggatggc tgtgttgatc ttcaccgact tcatatgcat ggccccaatc 1920tcattctatg ctctgtcagc aattctgaac aagcctctca tcactgttag caactccaaa 1980atcttgctgg tactcttcta tccacttaac tcctgtgcca atccattcct ctatgctatt 2040ttcaccaagg ccttccagag ggatgtgttc atcctactca gcaagtttgg catctgtaaa 2100cgccaggctc aggcataccg ggggcagagg gttcctccaa agaacagcac tgatattcag 2160gttcaaaagg ttacccacga gatgaggcag ggtctccaca acatggaaga tgtctatgaa 2220ctgattgaaa agtcccatct aaccccaaag aagcaaggcc aaatctcaga agagtatatg 2280caaacggttt tg 2292<210>399<211>764<212>PRT<213>智人(Homo sapiens)<400>399Met Arg Pro Ala Asp Leu Leu Gln Leu Val Leu Leu Leu Asp Leu Pro1 5 10 15Arg Asp Leu Gly Gly Met Gly Cys Ser Ser Pro Pro Cys Glu Cys His
20 25 30Gln Glu Glu Asp Phe Arg Val Thr Cys Lys Asp Ile Gln Arg Ile Pro
35 40 45Ser Leu Pro Pro Ser Thr Gln Thr Leu Lys Leu Ile Glu Thr His Leu
50 55 60Arg Thr Ile Pro Ser His Ala Phe Ser Asn Leu Pro Asn Ile Ser Arg65 70 75 80Ile Tyr Val Ser Ile Asp Val Thr Leu Gln Gln Leu Glu Ser His Ser
85 90 95Phe Tyr Asn Leu Ser Lys Val Thr His Ile Glu Ile Arg Asn Thr Arg
100 105 110Asn Leu Thr Tyr Ile Asp Pro Asp Ala Leu Lys Glu Leu Pro Leu Leu
115 120 125Lys Phe Leu Gly Ile Phe Asn Thr Gly Leu Lys Met Phe Pro Asp Leu
130 135 140Thr Lys Val Tyr Ser Thr Asp Ile Phe Phe Ile Leu Glu Ile Thr Asp145 150 155 160Asn Pro Tyr Met Thr Ser Ile Pro Val Asn Ala Phe Gln Gly Leu Cys
165 170 175Asn Glu Thr Leu Thr Leu Lys Leu Tyr Asn Asn Gly Phe Thr Ser Val
180 185 190Gln Gly Tyr Ala Phe Asn Gly Thr Lys Leu Asp Ala Val Tyr Leu Asn
195 200 205Lys Asn Lys Tyr Leu Thr Val Ile Asp Lys Asp Ala Phe Gly Gly Val
210 215 220Tyr Ser Gly Pro Ser Leu Leu Asp Val Ser Gln Thr Ser Val Thr Ala225 230 235 240Leu Pro Ser Lys Gly Leu Glu His Leu Lys Glu Leu Ile Ala Arg Asn
245 250 255Thr Trp Thr Leu Lys Lys Leu Pro Leu Ser Leu Ser Phe Leu His Leu
260 265 270Thr Arg Ala Asp Leu Ser Tyr Pro Ser His Cys Cys Ala Phe Lys Asn
275 280 285Gln Lys Lys Ile Arg Gly Ile Leu Glu Ser Leu Met Cys Asn Glu Ser
290 295 300Ser Met Gln Ser Leu Arg Gln Arg Lys Ser Val Asn Ala Leu Asn Ser305 310 315 320Pro Leu His Gln Glu Tyr Glu Glu Asn Leu Gly Asp Ser Ile Val Gly
325 330 335Tyr Lys Glu Lys Ser Lys Phe Gln Asp Thr His Asn Asn Ala His Tyr
340 345 350Tyr Val Phe Phe Glu Glu Gln Glu Asp Glu Ile Ile Gly Phe Gly Gln
355 360 365Glu Leu Lys Asn Pro Gln Glu Glu Thr Leu Gln Ala Phe Asp Ser His
370 375 380Tyr Asp Tyr Thr Ile Cys Gly Asp Ser Glu Asp Met Val Cys Thr Pro385 390 395 400Lys Ser Asp Glu Phe Asn Pro Cys Glu Asp Ile Met Gly Tyr Lys Phe
405 410 415Leu Arg Ile Val Val Trp Phe Val Ser Leu Leu Ala Leu Leu Gly Asn
420 425 430Val Phe Val Leu Leu Ile Leu Leu Thr Ser His Tyr Lys Leu Asn Val
435 440 445Pro Arg Phe Leu Met Cys Asn Leu Ala Phe Ala Asp Phe Cys Met Gly
450 455 460Met Tyr Leu Leu Leu Ile Ala Ser Val Asp Leu Tyr Thr His Ser Glu465 470 475 480Tyr Tyr Asn His Ala Ile Asp Trp Gln Thr Gly Pro Gly Cys Asn Thr
485 490 495Ala Gly Phe Phe Thr Val Phe Ala Ser Glu Leu Ser Val Tyr Thr Leu
500 505 510Thr Val Ile Thr Leu Glu Arg Trp Tyr Ala Ile Thr Phe Ala Met Arg
515 520 525Leu Asp Arg Lys Ile Arg Leu Arg His Ala Cys Ala Ile Met Val Gly
530 535 540Gly Trp Val Cys Cys Phe Leu Leu Ala Leu Leu Pro Leu Val Gly Ile545 550 555 560Ser Ser Tyr Ala Lys Val Ser Ile Cys Leu Pro Met Asp Thr Glu Thr
565 570 575Pro Leu Ala Leu Ala Tyr Ile Val Phe Val Leu Thr Leu Asn Ile Val
580 585 590Ala Phe Val Ile Val Cys Cys Cys Tyr Val Lys Ile Tyr Ile Thr Val
595 600 605Arg Asn Pro Gln Tyr Asn Pro Gly Asp Lys Gly Thr Lys Ile Ala Lys
610 615 620Arg Met Ala Val Leu Ile Phe Thr Asp Phe Ile Cys Met Ala Pro Ile625 630 635 640Ser Phe Tyr Ala Leu Ser Ala Ile Leu Asn Lys Pro Leu Ile Thr Val
645 650 655Ser Asn Ser Lys Ile Leu Leu Val Leu Phe Tyr Pro Leu Asn Ser Cys
660 665 670Ala Asn Pro Phe Leu Tyr Ala Ile Phe Thr Lys Ala Phe Gln Arg Asp
675 680 685Val Phe Ile Leu Leu Ser Lys Phe Gly Ile Cys Lys Arg Gln Ala Gln
690 695 700Ala Tyr Arg Gly Gln Arg Val Pro Pro Lys Asn Ser Thr Asp Ile Gln705 710 715 720Val Gln Lys Val Thr His Glu Met Arg Gln Gly Leu His Asn Met Glu
725 730 735Asp Val Tyr Glu Leu Ile Glu Lys Ser His Leu Thr Pro Lys Lys Gln
740 745 750Gly Gln Ile Ser Glu Glu Tyr Met Gln Thr Val Leu
755 760<210>400<211>32<212>DNA<213>智人(Homo sapiens)<400>400aaagatacca aaattatcaa gaggatggct gt 32<210>401<211>32<212>DNA<213>智人(Homo sapiens)<400>401acagccatcc tcttgataat tttggtatct tt 32<210>402<211>2292<212>DNA<213>智人(Homo sapiens)<400>402atgaggccgg cggacttgct gcagctggtg ctgctgctcg acctgcccag ggacctgggc 60ggaatggggt gttcgtctcc accctgcgag tgccatcagg aggaggactt cagagtcacc 120tgcaaggata ttcaacgcat ccccagctta ccgcccagta cgcagactct gaagcttatt 180gagactcacc tgagaactat tccaagtcat gcattttcta atctgcccaa tatttccaga 240atctacgtat ctatagatgt gactctgcag cagctggaat cacactcctt ctacaatttg 300agtaaagtga ctcacataga aattcggaat accaggaact taacttacat agaccctgat 360gccctcaaag agctccccct cctaaagttc cttggcattt tcaacactgg acttaaaatg 420ttccctgacc tgaccaaagt ttattccact gatatattct ttatacttga aattacagac 480aacccttaca tgacgtcaat ccctgtgaat gcttttcagg gactatgcaa tgaaaccttg 540acactgaagc tgtacaacaa cggctttact tcagtccaag gatatgcttt caatgggaca 600aagctggatg ctgtttacct aaacaagaat aaatacctga cagttattga caaagatgca 660tttggaggag tatacagtgg accaagcttg ctggacgtgt ctcaaaccag tgtcactgcc 720cttccatcca aaggcctgga gcacctgaag gaactgatag caagaaacac ctggactctt 780aagaaacttc cactttcctt gagtttcctt cacctcacac gggctgacct ttcttaccca 840agccactgct gtgcctttaa gaatcagaag aaaatcagag gaatccttga gtccttgatg 900tgtaatgaga gcagtatgca gagcttgcgc cagagaaaat ctgtgaatgc cttgaatagc 960cccctccacc aggaatatga agagaatctg ggtgacagca ttgttgggta caaggaaaag 1020tccaagttcc aggatactca taacaacgct cattattacg tcttctttga agaacaagag 1080gatgagatca ttggttttgg ccaggagctc aaaaaccccc aggaagagac tctacaagct 1140tttgacagcc attatgacta caccatatgt ggggacagtg aagacatggt gtgtaccccc 1200aagtccgatg agttcaaccc gtgtgaagac ataatgggct acaagttcct gagaattgtg 1260gtgtggttcg ttagtctgct ggctctcctg ggcaatgtct ttgtcctgct tattctcctc 1320accagccact acaaactgaa cgtcccccgc tttctcatgt gcaacctggc ctttgcggat 1380ttctgcatgg ggatgtacct gctcctcatc gcctctgtag acctctacac tcactctgag 1440tactacaacc atgccatcga ctggcagaca ggccctgggt gcaacacggc tggtttcttc 1500actgtctttg caagcgagtt atcggtgtat acgctgacgg tcatcaccct ggagcgctgg 1560tatgccatca ccttcgccat gcgcctggac cggaagatcc gcctcaggca cgcatgtgcc 1620atcatggttg ggggctgggt ttgctgcttc cttctcgccc tgcttccttt ggtgggaata 1680agtagctatg ccaaagtcag tatctgcctg cccatggaca ccgagacccc tcttgctctg 1740gcatatattg tttttgttct gacgctcaac atagttgcct tcgtcatcgt ctgctgctgt 1800tatgtgaaga tctacatcac agtccgaaat ccgcagtaca acccagggga caaagatacc 1860aaaattatca agaggatggc tgtgttgatc ttcaccgact tcatatgcat ggccccaatc 1920tcattctatg ctctgtcagc aattctgaac aagcctctca tcactgttag caactccaaa 1980atcttgctgg tactcttcta tccacttaac tcctgtgcca atccattcct ctatgctatt 2040ttcaccaagg ccttccagag ggatgtgttc atcctactca gcaagtttgg catctgtaaa 2100cgccaggctc aggcataccg ggggcagagg gttcctccaa agaacagcac tgatattcag 2160gttcaaaagg ttacccacga gatgaggcag ggtctccaca acatggaaga tgtctatgaa 2220ctgattgaaa agtcccatct aaccccaaag aagcaaggcc aaatctcaga agagtatatg 2280caaacggttt tg 2292<210>403<211>764<212>PRT<213>智人(Homo sapiens)<400>403Met Arg Pro Ala Asp Leu Leu Gln Leu Val Leu Leu Leu Asp Leu Pro1 5 10 15Arg Asp Leu Gly Gly Met Gly Cys Ser Ser Pro Pro Cys Glu Cys His
20 25 30Gln Glu Glu Asp Phe Arg Val Thr Cys Lys Asp Ile Gln Arg Ile Pro
35 40 45Ser Leu Pro Pro Ser Thr Gln Thr Leu Lys Leu Ile Glu Thr His Leu
50 55 60Arg Thr Ile Pro Ser His Ala Phe Ser Asn Leu Pro Asn Ile Ser Arg65 70 75 80Ile Tyr Val Ser Ile Asp Val Thr Leu Gln Gln Leu Glu Ser His Ser
85 90 95Phe Tyr Asn Leu Ser Lys Val Thr His Ile Glu Ile Arg Asn Thr Arg
100 105 110Asn Leu Thr Tyr Ile Asp Pro Asp Ala Leu Lys Glu Leu Pro Leu Leu
115 120 125Lys Phe Leu Gly Ile Phe Asn Thr Gly Leu Lys Met Phe Pro Asp Leu
130 135 140Thr Lys Val Tyr Ser Thr Asp Ile Phe Phe Ile Leu Glu Ile Thr Asp145 150 155 160Asn Pro Tyr Met Thr Ser Ile Pro Val Asn Ala Phe Gln Gly Leu Cys
165 170 175Asn Glu Thr Leu Thr Leu Lys Leu Tyr Asn Asn Gly Phe Thr Ser Val
180 185 190Gln Gly Tyr Ala Phe Asn Gly Thr Lys Leu Asp Ala Val Tyr Leu Asn
195 200 205Lys Asn Lys Tyr Leu Thr Val Ile Asp Lys Asp Ala Phe Gly Gly Val
210 215 220Tyr Ser Gly Pro Ser Leu Leu Asp Val Ser Gln Thr Ser Val Thr Ala225 230 235 240Leu Pro Ser Lys Gly Leu Glu His Leu Lys Glu Leu Ile Ala Arg Asn
245 250 255Thr Trp Thr Leu Lys Lys Leu Pro Leu Ser Leu Ser Phe Leu His Leu
260 265 270Thr Arg Ala Asp Leu Ser Tyr Pro Ser His Cys Cys Ala Phe Lys Asn
275 280 285Gln Lys Lys Ile Arg Gly Ile Leu Glu Ser Leu Met Cys Asn Glu Ser
290 295 300Ser Met Gln Ser Leu Arg Gln Arg Lys Ser Val Asn Ala Leu Asn Ser305 310 315 320Pro Leu His Gln Glu Tyr Glu Glu Asn Leu Gly Asp Ser Ile Val Gly
325 330 335Tyr Lys Glu Lys Ser Lys Phe Gln Asp Thr His Asn Asn Ala His Tyr
340 345 350Tyr Val Phe Phe Glu Glu Gln Glu Asp Glu Ile Ile Gly Phe Gly Gln
355 360 365Glu Leu Lys Asn Pro Gln Glu Glu Thr Leu Gln Ala Phe Asp Ser His
370 375 380Tyr Asp Tyr Thr Ile Cys Gly Asp Ser Glu Asp Met Val Cys Thr Pro385 390 395 400Lys Ser Asp Glu Phe Asn Pro Cys Glu Asp Ile Met Gly Tyr Lys Phe
405 410 415Leu Arg Ile Val Val Trp Phe Val Ser Leu Leu Ala Leu Leu Gly Asn
420 425 430Val Phe Val Leu Leu Ile Leu Leu Thr Ser His Tyr Lys Leu Asn Val
435 440 445Pro Arg Phe Leu Met Cys Asn Leu Ala Phe Ala Asp Phe Cys Met Gly
450 455 460Met Tyr Leu Leu Leu Ile Ala Ser Val Asp Leu Tyr Thr His Ser Glu465 470 475 480Tyr Tyr Asn His Ala Ile Asp Trp Gln Thr Gly Pro Gly Cys Asn Thr
485 490 495Ala Gly Phe Phe Thr Val Phe Ala Ser Glu Leu Ser Val Tyr Thr Leu
500 505 510Thr Val Ile Thr Leu Glu Arg Trp Tyr Ala Ile Thr Phe Ala Met Arg
515 520 525Leu Asp Arg Lys Ile Arg Leu Arg His Ala Cys Ala Ile Met Val Gly
530 535 540Gly Trp Val Cys Cys Phe Leu Leu Ala Leu Leu Pro Leu Val Gly Ile545 550 555 560Ser Ser Tyr Ala Lys Val Ser Ile Cys Leu Pro Met Asp Thr Glu Thr
565 570 575Pro Leu Ala Leu Ala Tyr Ile Val Phe Val Leu Thr Leu Asn Ile Val
580 585 590Ala Phe Val Ile Val Cys Cys Cys Tyr Val Lys Ile Tyr Ile Thr Val
595 600 605Arg Asn Pro Gln Tyr Asn Pro Gly Asp Lys Asp Thr Lys Ile Ile Lys
610 615 620Arg Met Ala Val Leu Ile Phe Thr Asp Phe Ile Cys Met Ala Pro Ile625 630 635 640Ser Phe Tyr Ala Leu Ser Ala Ile Leu Asn Lys Pro Leu Ile Thr Val
645 650 655Ser Asn Ser Lys Ile Leu Leu Val Leu Phe Tyr Pro Leu Asn Ser Cys
660 665 670Ala Asn Pro Phe Leu Tyr Ala Ile Phe Thr Lys Ala Phe Gln Arg Asp
675 680 685Val Phe Ile Leu Leu Ser Lys Phe Gly Ile Cys Lys Arg Gln Ala Gln
690 695 700Ala Tyr Arg Gly Gln Arg Val Pro Pro Lys Asn Ser Thr Asp Ile Gln705 710 715 720Val Gln Lys Val Thr His Glu Met Arg Gln Gly Leu His Asn Met Glu
725 730 735Asp Val Tyr Glu Leu Ile Glu Lys Ser His Leu Thr Pro Lys Lys Gln
740 745 750Gly Gln Ile Ser Glu Glu Tyr Met Gln Thr Val Leu
755 760<210>404<211>33<212>DNA<213>智人(Homo sapiens)<400>404aaagatacca aaattaagaa gaggatggct gtg 33<210>405<211>33<212>DNA<213>智人(Homo sapiens)<400>405cacagccatc ctcttcttaa ttttggtatc ttt 33<210>406<211>2292<212>DNA<213>智人(Homo sapiens)<400>406atgaggccgg cggacttgct gcagctggtg ctgctgctcg acctgcccag ggacctgggc 60ggaatggggt gttcgtctcc accctgcgag tgccatcagg aggaggactt cagagtcacc 120tgcaaggata ttcaacgcat ccccagctta ccgcccagta cgcagactct gaagcttatt 180gagactcacc tgagaactat tccaagtcat gcattttcta atctgcccaa tatttccaga 240atctacgtat ctatagatgt gactctgcag cagctggaat cacactcctt ctacaatttg 300agtaaagtga ctcacataga aattcggaat accaggaact taacttacat agaccctgat 360gccctcaaag agctccccct cctaaagttc cttggcattt tcaacactgg acttaaaatg 420ttccctgacc tgaccaaagt ttattccact gatatattct ttatacttga aattacagac 480aacccttaca tgacgtcaat ccctgtgaat gcttttcagg gactatgcaa tgaaaccttg 540acactgaagc tgtacaacaa cggctttact tcagtccaag gatatgcttt caatgggaca 600aagctggatg ctgtttacct aaacaagaat aaatacctga cagttattga caaagatgca 660tttggaggag tatacagtgg accaagcttg ctggacgtgt ctcaaaccag tgtcactgcc 720cttccatcca aaggcctgga gcacctgaag gaactgatag caagaaacac ctggactctt 780aagaaacttc cactttcctt gagtttcctt cacctcacac gggctgacct ttcttaccca 840agccactgct gtgcctttaa gaatcagaag aaaatcagag gaatccttga gtccttgatg 900tgtaatgaga gcagtatgca gagcttgcgc cagagaaaat ctgtgaatgc cttgaatagc 960cccctccacc aggaatatga agagaatctg ggtgacagca ttgttgggta caaggaaaag 1020tccaagttcc aggatactca taacaacgct cattattacg tcttctttga agaacaagag 1080gatgagatca ttggttttgg ccaggagctc aaaaaccccc aggaagagac tctacaagct 1140tttgacagcc attatgacta caccatatgt ggggacagtg aagacatggt gtgtaccccc 1200aagtccgatg agttcaaccc gtgtgaagac ataatgggct acaagttcct gagaattgtg 1260gtgtggttcg ttagtctgct ggctctcctg ggcaatgtct ttgtcctgct tattctcctc 1320accagccact acaaactgaa cgtcccccgc tttctcatgt gcaacctggc ctttgcggat 1380ttctgcatgg ggatgtacct gctcctcatc gcctctgtag acctctacac tcactctgag 1440tactacaacc atgccatcga ctggcagaca ggccctgggt gcaacacggc tggtttcttc 1500actgtctttg caagcgagtt atcggtgtat acgctgacgg tcatcaccct ggagcgctgg 1560tatgccatca ccttcgccat gcgcctggac cggaagatcc gcctcaggca cgcatgtgcc 1620atcatggttg ggggctgggt ttgctgcttc cttctcgccc tgcttccttt ggtgggaata 1680agtagctatg ccaaagtcag tatctgcctg cccatggaca ccgagacccc tcttgctctg 1740gcatatattg tttttgttct gacgctcaac atagttgcct tcgtcatcgt ctgctgctgt 1800tatgtgaaga tctacatcac agtccgaaat ccgcagtaca acccagggga caaagatacc 1860aaaattaaga agaggatggc tgtgttgatc ttcaccgact tcatatgcat ggccccaatc 1920tcattctatg ctctgtcagc aattctgaac aagcctctca tcactgttag caactccaaa 1980atcttgctgg tactcttcta tccacttaac tcctgtgcca atccattcct ctatgctatt 2040ttcaccaagg ccttccagag ggatgtgttc atcctactca gcaagtttgg catctgtaaa 2100cgccaggctc aggcataccg ggggcagagg gttcctccaa agaacagcac tgatattcag 2160gttcaaaagg ttacccacga gatgaggcag ggtctccaca acatggaaga tgtctatgaa 2220ctgattgaaa agtcccatct aaccccaaag aagcaaggcc aaatctcaga agagtatatg 2280caaacggttt tg 2292<210>407<211>764<212>PRT<213>智人(Homo sapiens)<400>407Met Arg Pro Ala Asp Leu Leu Gln Leu Val Leu Leu Leu Asp Leu Pro1 5 10 15Arg Asp Leu Gly Gly Met Gly Cys Ser Ser Pro Pro Cys Glu Cys His
20 25 30Gln Glu Glu Asp Phe Arg Val Thr Cys Lys Asp Ile Gln Arg Ile Pro
35 40 45Ser Leu Pro Pro Ser Thr Gln Thr Leu Lys Leu Ile Glu Thr His Leu
50 55 60Arg Thr Ile Pro Ser His Ala Phe Ser Asn Leu Pro Asn Ile Ser Arg65 70 75 80Ile Tyr Val Ser Ile Asp Val Thr Leu Gln Gln Leu Glu Ser His Ser
85 90 95Phe Tyr Asn Leu Ser Lys Val Thr His Ile Glu Ile Arg Asn Thr Arg
100 105 110Asn Leu Thr Tyr Ile Asp Pro Asp Ala Leu Lys Glu Leu Pro Leu Leu
115 120 125Lys Phe Leu Gly Ile Phe Asn Thr Gly Leu Lys Met Phe Pro Asp Leu
130 135 140Thr Lys Val Tyr Ser Thr Asp Ile Phe Phe Ile Leu Glu Ile Thr Asp145 150 155 160Asn Pro Tyr Met Thr Ser Ile Pro Val Asn Ala Phe Gln Gly Leu Cys
165 170 175Asn Glu Thr Leu Thr Leu Lys Leu Tyr Asn Asn Gly Phe Thr Ser Val
180 185 190Gln Gly Tyr Ala Phe Asn Gly Thr Lys Leu Asp Ala Val Tyr Leu Asn
195 200 205Lys Asn Lys Tyr Leu Thr Val Ile Asp Lys Asp Ala Phe Gly Gly Val
210 215 220Tyr Ser Gly Pro Ser Leu Leu Asp Val Ser Gln Thr Ser Val Thr Ala225 230 235 240Leu Pro Ser Lys Gly Leu Glu His Leu Lys Glu Leu Ile Ala Arg Asn
245 250 255Thr Trp Thr Leu Lys Lys Leu Pro Leu Ser Leu Ser Phe Leu His Leu
260 265 270Thr Arg Ala Asp Leu Ser Tyr Pro Ser His Cys Cys Ala Phe Lys Asn
275 280 285Gln Lys Lys Ile Arg Gly Ile Leu Glu Ser Leu Met Cys Asn Glu Ser
290 295 300Ser Met Gln Ser Leu Arg Gln Arg Lys Ser Val Asn Ala Leu Asn Ser305 310 315 320Pro Leu His Gln Glu Tyr Glu Glu Asn Leu Gly Asp Ser Ile Val Gly
325 330 335Tyr Lys Glu Lys Ser Lys Phe Gln Asp Thr His Asn Asn Ala His Tyr
340 345 350Tyr Val Phe Phe Glu Glu Gln Glu Asp Glu Ile Ile Gly Phe Gly Gln
355 360 365Glu Leu Lys Asn Pro Gln Glu Glu Thr Leu Gln Ala Phe Asp Ser His
370 375 380Tyr Asp Tyr Thr Ile Cys Gly Asp Ser Glu Asp Met Val Cys Thr Pro385 390 395 400Lys Ser Asp Glu Phe Asn Pro Cys Glu Asp Ile Met Gly Tyr Lys Phe
405 410 415Leu Arg Ile Val Val Trp Phe Val Ser Leu Leu Ala Leu Leu Gly Asn
420 425 430Val Phe Val Leu Leu Ile Leu Leu Thr Ser His Tyr Lys Leu Asn Val
435 440 445Pro Arg Phe Leu Met Cys Asn Leu Ala Phe Ala Asp Phe Cys Met Gly
450 455 460Met Tyr Leu Leu Leu Ile Ala Ser Val Asp Leu Tyr Thr His Ser Glu465 470 475 480Tyr Tyr Asn His Ala Ile Asp Trp Gln Thr Gly Pro Gly Cys Asn Thr
485 490 495Ala Gly Phe Phe Thr Val Phe Ala Ser Glu Leu Ser Val Tyr Thr Leu
500 505 510Thr Val Ile Thr Leu Glu Arg Trp Tyr Ala Ile Thr Phe Ala Met Arg
515 520 525Leu Asp Arg Lys Ile Arg Leu Arg His Ala Cys Ala Ile Met Val Gly
530 535 540Gly Trp Val Cys Cys Phe Leu Leu Ala Leu Leu Pro Leu Val Gly Ile545 550 555 560Ser Ser Tyr Ala Lys Val Ser Ile Cys Leu Pro Met Asp Thr Glu Thr
565 570 575Pro Leu Ala Leu Ala Tyr Ile Val Phe Val Leu Thr Leu Asn Ile Val
580 585 590Ala Phe Val Ile Val Cys Cys Cys Tyr Val Lys Ile Tyr Ile Thr Val
595 600 605Arg Asn Pro Gln Tyr Asn Pro Gly Asp Lys Asp Thr Lys Ile Lys Lys
610 615 620Arg Met Ala Val Leu Ile Phe Thr Asp Phe Ile Cys Met Ala Pro Ile625 630 635 640Ser Phe Tyr Ala Leu Ser Ala Ile Leu Asn Lys Pro Leu Ile Thr Val
645 650 655Ser Asn Ser Lys Ile Leu Leu Val Leu Phe Tyr Pro Leu Asn Ser Cys
660 665 670Ala Asn Pro Phe Leu Tyr Ala Ile Phe Thr Lys Ala Phe Gln Arg Asp
675 680 685Val Phe Ile Leu Leu Ser Lys Phe Gly Ile Cys Lys Arg Gln Ala Gln
690 695 700Ala Tyr Arg Gly Gln Arg Val Pro Pro Lys Asn Ser Thr Asp Ile Gln705 710 715 720Val Gln Lys Val Thr His Glu Met Arg Gln Gly Leu His Asn Met Glu
725 730 735Asp Val Tyr Glu Leu Ile Glu Lys Ser His Leu Thr Pro Lys Lys Gln
740 745 750Gly Gln Ile Ser Glu Glu Tyr Met Gln Thr Val Leu
755 760<210>408<211>34<212>DNA<213>智人(Homo sapiens)<400>408ctatccactt aactcgtacg ccaatccatt cctc 34<210>409<211>34<212>DNA<213>智人(Homo sapiens)<400>409gaggaatgga ttggcgtacg agttaagtgg atag 34<210>410<211>2292<212>DNA<213>智人(Homo sapiens)<400>410atgaggccgg cggacttgct gcagctggtg ctgctgctcg acctgcccag ggacctgggc 60ggaatggggt gttcgtctcc accctgcgag tgccatcagg aggaggactt cagagtcacc 120tgcaaggata ttcaacgcat ccccagctta ccgcccagta cgcagactct gaagcttatt 180gagactcacc tgagaactat tccaagtcat gcattttcta atctgcccaa tatttccaga 240atctacgtat ctatagatgt gactctgcag cagctggaat cacactcctt ctacaatttg 300agtaaagtga ctcacataga aattcggaat accaggaact taacttacat agaccctgat 360gccctcaaag agctccccct cctaaagttc cttggcattt tcaacactgg acttaaaatg 420ttccctgacc tgaccaaagt ttattccact gatatattct ttatacttga aattacagac 480aacccttaca tgacgtcaat ccctgtgaat gcttttcagg gactatgcaa tgaaaccttg 540acactgaagc tgtacaacaa cggctttact tcagtccaag gatatgcttt caatgggaca 600aagctggatg ctgtttacct aaacaagaat aaatacctga cagttattga caaagatgca 660tttggaggag tatacagtgg accaagcttg ctggacgtgt ctcaaaccag tgtcactgcc 720cttccatcca aaggcctgga gcacctgaag gaactgatag caagaaacac ctggactctt 780aagaaacttc cactttcctt gagtttcctt cacctcacac gggctgacct ttcttaccca 840agccactgct gtgcctttaa gaatcagaag aaaatcagag gaatccttga gtccttgatg 900tgtaatgaga gcagtatgca gagcttgcgc cagagaaaat ctgtgaatgc cttgaatagc 960cccctccacc aggaatatga agagaatctg ggtgacagca ttgttgggta caaggaaaag 1020tccaagttcc aggatactca taacaacgct cattattacg tcttctttga agaacaagag 1080gatgagatca ttggttttgg ccaggagctc aaaaaccccc aggaagagac tctacaagct 1140tttgacagcc attatgacta caccatatgt ggggacagtg aagacatggt gtgtaccccc 1200aagtccgatg agttcaaccc gtgtgaagac ataatgggct acaagttcct gagaattgtg 1260gtgtggttcg ttagtctgct ggctctcctg ggcaatgtct ttgtcctgct tattctcctc 1320accagccact acaaactgaa cgtcccccgc tttctcatgt gcaacctggc ctttgcggat 1380ttctgcatgg ggatgtacct gctcctcatc gcctctgtag acctctacac tcactctgag 1440tactacaacc atgccatcga ctggcagaca ggccctgggt gcaacacggc tggtttcttc 1500actgtctttg caagcgagtt atcggtgtat acgctgacgg tcatcaccct ggagcgctgg 1560tatgccatca ccttcgccat gcgcctggac cggaagatcc gcctcaggca cgcatgtgcc 1620atcatggttg ggggctgggt ttgctgcttc cttctcgccc tgcttccttt ggtgggaata 1680agtagctatg ccaaagtcag tatctgcctg cccatggaca ccgagacccc tcttgctctg 1740gcatatattg tttttgttct gacgctcaac atagttgcct tcgtcatcgt ctgctgctgt 1800tatgtgaaga tctacatcac agtccgaaat ccgcagtaca acccagggga caaagatacc 1860aaaattgcca agaggatggc tgtgttgatc ttcaccgact tcatatgcat ggccccaatc 1920tcattctatg ctctgtcagc aattctgaac aagcctctca tcactgttag caactccaaa 1980atcttgctgg tactcttcta tccacttaac tcctacgcca atccattcct ctatgctatt 2040ttcaccaagg ccttccagag ggatgtgttc atcctactca gcaagtttgg catctgtaaa 2100cgccaggctc aggcataccg ggggcagagg gttcctccaa agaacagcac tgatattcag 2160gttcaaaagg ttacccacga gatgaggcag ggtctccaca acatggaaga tgtctatgaa 2220ctgattgaaa agtcccatct aaccccaaag aagcaaggcc aaatctcaga agagtatatg 2280caaacggttt tg 2292<210>411<211>764<212>PRT<213>智人(Homo sapiens)<400>411Met Arg Pro Ala Asp Leu Leu Gln Leu Val Leu Leu Leu Asp Leu Pro1 5 10 15Arg Asp Leu Gly Gly Met Gly Cys Ser Ser Pro Pro Cys Glu Cys His
20 25 30Gln Glu Glu Asp Phe Arg Val Thr Cys Lys Asp Ile Gln Arg Ile Pro
35 40 45Ser Leu Pro Pro Ser Thr Gln Thr Leu Lys Leu Ile Glu Thr His Leu
50 55 60Arg Thr Ile Pro Ser His Ala Phe Ser Asn Leu Pro Asn Ile Ser Arg65 70 75 80Ile Tyr Val Ser Ile Asp Val Thr Leu Gln Gln Leu Glu Ser His Ser
85 90 95Phe Tyr Asn Leu Ser Lys Val Thr His Ile Glu Ile Arg Asn Thr Arg
100 105 110Asn Leu Thr Tyr Ile Asp Pro Asp Ala Leu Lys Glu Leu Pro Leu Leu
115 120 125Lys Phe Leu Gly Ile Phe Asn Thr Gly Leu Lys Met Phe Pro Asp Leu
130 135 140Thr Lys Val Tyr Ser Thr Asp Ile Phe Phe Ile Leu Glu Ile Thr Asp145 150 155 160Asn Pro Tyr Met Thr Ser Ile Pro Val Asn Ala Phe Gln Gly Leu Cys
165 170 175Asn Glu Thr Leu Thr Leu Lys Leu Tyr Asn Asn Gly Phe Thr Ser Val
180 185 190Gln Gly Tyr Ala Phe Asn Gly Thr Lys Leu Asp Ala Val Tyr Leu Asn
195 200 205Lys Asn Lys Tyr Leu Thr Val Ile Asp Lys Asp Ala Phe Gly Gly Val
210 215 220Tyr Ser Gly Pro Ser Leu Leu Asp Val Ser Gln Thr Ser Val Thr Ala225 230 235 240Leu Pro Ser Lys Gly Leu Glu His Leu Lys Glu Leu Ile Ala Arg Asn
245 250 255Thr Trp Thr Leu Lys Lys Leu Pro Leu Ser Leu Ser Phe Leu His Leu
260 265 270Thr Arg Ala Asp Leu Ser Tyr Pro Ser His Cys Cys Ala Phe Lys Asn
275 280 285Gln Lys Lys Ile Arg Gly Ile Leu Glu Ser Leu Met Cys Asn Glu Ser
290 295 300Ser Met Gln Ser Leu Arg Gln Arg Lys Ser Val Asn Ala Leu Asn Ser305 310 315 320Pro Leu His Gln Glu Tyr Glu Glu Asn Leu Gly Asp Ser Ile Val Gly
325 330 335Tyr Lys Glu Lys Ser Lys Phe Gln Asp Thr His Asn Asn Ala His Tyr
340 345 350Tyr Val Phe Phe Glu Glu Gln Glu Asp Glu Ile Ile Gly Phe Gly Gln
355 360 365Glu Leu Lys Asn Pro Gln Glu Glu Thr Leu Gln Ala Phe Asp Ser His
370 375 380Tyr Asp Tyr Thr Ile Cys Gly Asp Ser Glu Asp Met Val Cys Thr Pro385 390 395 400Lys Ser Asp Glu Phe Asn Pro Cys Glu Asp Ile Met Gly Tyr Lys Phe
405 410 415Leu Arg Ile Val Val Trp Phe Val Ser Leu Leu Ala Leu Leu Gly Asn
420 425 430Val Phe Val Leu Leu Ile Leu Leu Thr Ser His Tyr Lys Leu Asn Val
435 440 445Pro Arg Phe Leu Met Cys Asn Leu Ala Phe Ala Asp Phe Cys Met Gly
450 455 460Met Tyr Leu Leu Leu Ile Ala Ser Val Asp Leu Tyr Thr His Ser Glu465 470 475 480Tyr Tyr Asn His Ala Ile Asp Trp Gln Thr Gly Pro Gly Cys Asn Thr
485 490 495Ala Gly Phe Phe Thr Val Phe Ala Ser Glu Leu Ser Val Tyr Thr Leu
500 505 510Thr Val Ile Thr Leu Glu Arg Trp Tyr Ala Ile Thr Phe Ala Met Arg
515 520 525Leu Asp Arg Lys Ile Arg Leu Arg His Ala Cys Ala Ile Met Val Gly
530 535 540Gly Trp Val Cys Cys Phe Leu Leu Ala Leu Leu Pro Leu Val Gly Ile545 550 555 560Ser Ser Tyr Ala Lys Val Ser Ile Cys Leu Pro Met Asp Thr Glu Thr
565 570 575Pro Leu Ala Leu Ala Tyr Ile Val Phe Val Leu Thr Leu Asn Ile Val
580 585 590Ala Phe Val Ile Val Cys Cys Cys Tyr Val Lys Ile Tyr Ile Thr Val
595 600 605Arg Asn Pro Gln Tyr Asn Pro Gly Asp Lys Asp Thr Lys Ile Ala Lys
610 615 620Arg Met Ala Val Leu Ile Phe Thr Asp Phe Ile Cys Met Ala Pro Ile625 630 635 640Ser Phe Tyr Ala Leu Ser Ala Ile Leu Asn Lys Pro Leu Ile Thr Val
645 650 655Ser Asn Ser Lys Ile Leu Leu Val Leu Phe Tyr Pro Leu Asn Ser Tyr
660 665 670Ala Asn Pro Phe Leu Tyr Ala Ile Phe Thr Lys Ala Phe Gln Arg Asp
675 680 685Val Phe Ile Leu Leu Ser Lys Phe Gly Ile Cys Lys Arg Gln Ala Gln
690 695 700Ala Tyr Arg Gly Gln Arg Val Pro Pro Lys Asn Ser Thr Asp Ile Gln705 710 715 720Val Gln Lys Val Thr His Glu Met Arg Gln Gly Leu His Asn Met Glu
725 730 735Asp Val Tyr Glu Leu Ile Glu Lys Ser His Leu Thr Pro Lys Lys Gln
740 745 750Gly Gln Ile Ser Glu Glu Tyr Met Gln Thr Val Leu
755 760<210>412<211>44<212>DNA<213>智人(Homo sapiens)<400>412acccagggga caaaggtacc aaaattaaga agaggatggc tgtg 44<210>413<211>44<212>DNA<213>智人(Homo sapiens)<400>413cacagccatc ctcttcttaa ttttggtacc tttgtcccct gggt 44<210>414<211>2292<212>DNA<213>智人(Homo sapiens)<400>414atgaggccgg cggacttgct gcagctggtg ctgctgctcg acctgcccag ggacctgggc 60ggaatggggt gttcgtctcc accctgcgag tgccatcagg aggaggactt cagagtcacc 120tgcaaggata ttcaacgcat ccccagctta ccgcccagta cgcagactct gaagcttatt 180gagactcacc tgagaactat tccaagtcat gcattttcta atctgcccaa tatttccaga 240atctacgtat ctatagatgt gactctgcag cagctggaat cacactcctt ctacaatttg 300agtaaagtga ctcacataga aattcggaat accaggaact taacttacat agaccctgat 360gccctcaaag agctccccct cctaaagttc cttggcattt tcaacactgg acttaaaatg 420ttccctgacc tgaccaaagt ttattccact gatatattct ttatacttga aattacagac 480aacccttaca tgacgtcaat ccctgtgaat gcttttcagg gactatgcaa tgaaaccttg 540acactgaagc tgtacaacaa cggctttact tcagtccaag gatatgcttt caatgggaca 600aagctggatg ctgtttacct aaacaagaat aaatacctga cagttattga caaagatgca 660tttggaggag tatacagtgg accaagcttg ctggacgtgt ctcaaaccag tgtcactgcc 720cttccatcca aaggcctgga gcacctgaag gaactgatag caagaaacac ctggactctt 780aagaaacttc cactttcctt gagtttcctt cacctcacac gggctgacct ttcttaccca 840agccactgct gtgcctttaa gaatcagaag aaaatcagag gaatccttga gtccttgatg 900tgtaatgaga gcagtatgca gagcttgcgc cagagaaaat ctgtgaatgc cttgaatagc 960cccctccacc aggaatatga agagaatctg ggtgacagca ttgttgggta caaggaaaag 1020tccaagttcc aggatactca taacaacgct cattattacg tcttctttga agaacaagag 1080gatgagatca ttggttttgg ccaggagctc aaaaaccccc aggaagagac tctacaagct 1140tttgacagcc attatgacta caccatatgt ggggacagtg aagacatggt gtgtaccccc 1200aagtccgatg agttcaaccc gtgtgaagac ataatgggct acaagttcct gagaattgtg 1260gtgtggttcg ttagtctgct ggctctcctg ggcaatgtct ttgtcctgct tattctcctc 1320accagccact acaaactgaa cgtcccccgc tttctcatgt gcaacctggc ctttgcggat 1380ttctgcatgg ggatgtacct gctcctcatc gcctctgtag acctctacac tcactctgag 1440tactacaacc atgccatcga ctggcagaca ggccctgggt gcaacacggc tggtttcttc 1500actgtctttg caagcgagtt atcggtgtat acgctgacgg tcatcaccct ggagcgctgg 1560tatgccatca ccttcgccat gcgcctggac cggaagatcc gcctcaggca cgcatgtgcc 1620atcatggttg ggggctgggt ttgctgcttc cttctcgccc tgcttccttt ggtgggaata 1680agtagctatg ccaaagtcag tatctgcctg cccatggaca ccgagacccc tcttgctctg 1740gcatatattg tttttgttct gacgctcaac atagttgcct tcgtcatcgt ctgctgctgt 1800tatgtgaaga tctacatcac agtccgaaat ccgcagtaca acccagggga caaaggtacc 1860aaaattaaga agaggatggc tgtgttgatc ttcaccgact tcatatgcat ggccccaatc 1920tcattctatg ctctgtcagc aattctgaac aagcctctca tcactgttag caactccaaa 1980atcttgctgg tactcttcta tccacttaac tcctgtgcca atccattcct ctatgctatt 2040ttcaccaagg ccttccagag ggatgtgttc atcctactca gcaagtttgg catctgtaaa 2100cgccaggctc aggcataccg ggggcagagg gttcctccaa agaacagcac tgatattcag 2160gttcaaaagg ttacccacga gatgaggcag ggtctccaca acatggaaga tgtctatgaa 2220ctgattgaaa agtcccatct aaccccaaag aagcaaggcc aaatctcaga agagtatatg 2280caaacggttt tg 2292<210>415<211>764<212>PRT<213>智人(Homo sapiens)<400>415Met Arg Pro Ala Asp Leu Leu Gln Leu Val Leu Leu Leu Asp Leu Pro1 5 10 15Arg Asp Leu Gly Gly Met Gly Cys Ser Ser Pro Pro Cys Glu Cys His
20 25 30Gln Glu Glu Asp Phe Arg Val Thr Cys Lys Asp Ile Gln Arg Ile Pro
35 40 45Ser Leu Pro Pro Ser Thr Gln Thr Leu Lys Leu Ile Glu Thr His Leu
50 55 60Arg Thr Ile Pro Ser His Ala Phe Ser Asn Leu Pro Asn Ile Ser Arg65 70 75 80Ile Tyr Val Ser Ile Asp Val Thr Leu Gln Gln Leu Glu Ser His Ser
85 90 95Phe Tyr Asn Leu Ser Lys Val Thr His Ile Glu Ile Arg Asn Thr Arg
100 105 110Asn Leu Thr Tyr Ile Asp Pro Asp Ala Leu Lys Glu Leu Pro Leu Leu
115 120 125Lys Phe Leu Gly Ile Phe Asn Thr Gly Leu Lys Met Phe Pro Asp Leu
130 135 140Thr Lys Val Tyr Ser Thr Asp Ile Phe Phe Ile Leu Glu Ile Thr Asp145 150 155 160Asn Pro Tyr Met Thr Ser Ile Pro Val Asn Ala Phe Gln Gly Leu Cys
165 170 175Asn Glu Thr Leu Thr Leu Lys Leu Tyr Asn Asn Gly Phe Thr Ser Val
180 185 190Gln Gly Tyr Ala Phe Asn Gly Thr Lys Leu Asp Ala Val Tyr Leu Asn
195 200 205Lys Asn Lys Tyr Leu Thr Val Ile Asp Lys Asp Ala Phe Gly Gly Val
210 215 220Tyr Ser Gly Pro Ser Leu Leu Asp Val Ser Gln Thr Ser Val Thr Ala225 230 235 240Leu Pro Ser Lys Gly Leu Glu His Leu Lys Glu Leu Ile Ala Arg Asn
245 250 255Thr Trp Thr Leu Lys Lys Leu Pro Leu Ser Leu Ser Phe Leu His Leu
260 265 270Thr Arg Ala Asp Leu Ser Tyr Pro Ser His Cys Cys Ala Phe Lys Asn
275 280 285Gln Lys Lys Ile Arg Gly Ile Leu Glu Ser Leu Met Cys Asn Glu Ser
290 295 300Ser Met Gln Ser Leu Arg Gln Arg Lys Ser Val Asn Ala Leu Asn Ser305 310 315 320Pro Leu His Gln Glu Tyr Glu Glu Asn Leu Gly Asp Ser Ile Val Gly
325 330 335Tyr Lys Glu Lys Ser Lys Phe Gln Asp Thr His Asn Asn Ala His Tyr
340 345 350Tyr Val Phe Phe Glu Glu Gln Glu Asp Glu Ile Ile Gly Phe Gly Gln
355 360 365Glu Leu Lys Asn Pro Gln Glu Glu Thr Leu Gln Ala Phe Asp Ser His
370 375 380Tyr Asp Tyr Thr Ile Cys Gly Asp Ser Glu Asp Met Val Cys Thr Pro385 390 395 400Lys Ser Asp Glu Phe Asn Pro Cys Glu Asp Ile Met Gly Tyr Lys Phe
405 410 415Leu Arg Ile Val Val Trp Phe Val Ser Leu Leu Ala Leu Leu Gly Asn
420 425 430Val Phe Val Leu Leu Ile Leu Leu Thr Ser His Tyr Lys Leu Asn Val
435 440 445Pro Arg Phe Leu Met Cys Asn Leu Ala Phe Ala Asp Phe Cys Met Gly
450 455 460Met Tyr Leu Leu Leu Ile Ala Ser Val Asp Leu Tyr Thr His Ser Glu465 470 475 480Tyr Tyr Asn His Ala Ile Asp Trp Gln Thr Gly Pro Gly Cys Asn Thr
485 490 495Ala Gly Phe Phe Thr Val Phe Ala Ser Glu Leu Ser Val Tyr Thr Leu
500 505 510Thr Val Ile Thr Leu Glu Arg Trp Tyr Ala Ile Thr Phe Ala Met Arg
515 520 525Leu Asp Arg Lys Ile Arg Leu Arg His Ala Cys Ala Ile Met Val Gly
530 535 540Gly Trp Val Cys Cys Phe Leu Leu Ala Leu Leu Pro Leu Val Gly Ile545 550 555 560Ser Ser Tyr Ala Lys Val Ser Ile Cys Leu Pro Met Asp Thr Glu Thr
565 570 575Pro Leu Ala Leu Ala Tyr Ile Val Phe Val Leu Thr Leu Asn Ile Val
580 585 590Ala Phe Val Ile Val Cys Cys Cys Tyr Val Lys Ile Tyr Ile Thr Val
595 600 605Arg Asn Pro Gln Tyr Asn Pro Gly Asp Lys Gly Thr Lys Ile Lys Lys
610 615 620Arg Met Ala Val Leu Ile Phe Thr Asp Phe Ile Cys Met Ala Pro Ile625 630 635 640Ser Phe Tyr Ala Leu Ser Ala Ile Leu Asn Lys Pro Leu Ile Thr Val
645 650 655Ser Asn Ser Lys Ile Leu Leu Val Leu Phe Tyr Pro Leu Asn Ser Cys
660 665 670Ala Asn Pro Phe Leu Tyr Ala Ile Phe Thr Lys Ala Phe Gln Arg Asp
675 680 685Val Phe Ile Leu Leu Ser Lys Phe Gly Ile Cys Lys Arg Gln Ala Gln
690 695 700Ala Tyr Arg Gly Gln Arg Val Pro Pro Lys Asn Ser Thr Asp Ile Gln705 710 715 720Val Gln Lys Val Thr His Glu Met Arg Gln Gly Leu His Asn Met Glu
725 730 735Asp Val Tyr Glu Leu Ile Glu Lys Ser His Leu Thr Pro Lys Lys Gln
740 745 750Gly Gln Ile Ser Glu Glu Tyr Met Gln Thr Val Leu
755 760<210>416<211>32<212>DNA<213>智人(Homo sapiens)<400>416caagcgagtt atcggcatat acgctgacgg tc 32<210>417<211>34<212>DNA<213>智人(Homo sapiens)<400>417gaggaatgga ttggcgtacg agttaagtgg atag 34<210>418<211>2292<212>DNA<213>智人(Homo sapiens)<400>418atgaggccgg cggacttgct gcagctggtg ctgctgctcg acctgcccag ggacctgggc 60ggaatggggt gttcgtctcc accctgcgag tgccatcagg aggaggactt cagagtcacc 120tgcaaggata ttcaacgcat ccccagctta ccgcccagta cgcagactct gaagcttatt 180gagactcacc tgagaactat tccaagtcat gcattttcta atctgcccaa tatttccaga 240atctacgtat ctatagatgt gactctgcag cagctggaat cacactcctt ctacaatttg 300agtaaagtga ctcacataga aattcggaat accaggaact taacttacat agaccctgat 360gccctcaaag agctccccct cctaaagttc cttggcattt tcaacactgg acttaaaatg 420ttccctgacc tgaccaaagt ttattccact gatatattct ttatacttga aattacagac 480aacccttaca tgacgtcaat ccctgtgaat gcttttcagg gactatgcaa tgaaaccttg 540acactgaagc tgtacaacaa cggctttact tcagtccaag gatatgcttt caatgggaca 600aagctggatg ctgtttacct aaacaagaat aaatacctga cagttattga caaagatgca 660tttggaggag tatacagtgg accaagcttg ctggacgtgt ctcaaaccag tgtcactgcc 720cttccatcca aaggcctgga gcacctgaag gaactgatag caagaaacac ctggactctt 780aagaaacttc cactttcctt gagtttcctt cacctcacac gggctgacct ttcttaccca 840agccactgct gtgcctttaa gaatcagaag aaaatcagag gaatccttga gtccttgatg 900tgtaatgaga gcagtatgca gagcttgcgc cagagaaaat ctgtgaatgc cttgaatagc 960cccctccacc aggaatatga agagaatctg ggtgacagca ttgttgggta caaggaaaag 1020tccaagttcc aggatactca taacaacgct cattattacg tcttctttga agaacaagag 1080gatgagatca ttggttttgg ccaggagctc aaaaaccccc aggaagagac tctacaagct 1140tttgacagcc attatgacta caccatatgt ggggacagtg aagacatggt gtgtaccccc 1200aagtccgatg agttcaaccc gtgtgaagac ataatgggct acaagttcct gagaattgtg 1260gtgtggttcg ttagtctgct ggctctcctg ggcaatgtct ttgtcctgct tattctcctc 1320accagccact acaaactgaa cgtcccccgc tttctcatgt gcaacctggc ctttgcggat 1380ttctgcatgg ggatgtacct gctcctcatc gcctctgtag acctctacac tcactctgag 1440tactacaacc atgccatcga ctggcagaca ggccctgggt gcaacacggc tggtttcttc 1500actgtctttg caagcgagtt atcggtgcat acgctgacgg tcatcaccct ggagcgctgg 1560tatgccatca ccttcgccat gcgcctggac cggaagatcc gcctcaggca cgcatgtgcc 1620atcatggttg ggggctgggt ttgctgcttc cttctcgccc tgcttccttt ggtgggaata 1680agtagctatg ccaaagtcag tatctgcctg cccatggaca ccgagacccc tcttgctctg 1740gcatatattg tttttgttct gacgctcaac atagttgcct tcgtcatcgt ctgctgctgt 1800tatgtgaaga tctacatcac agtccgaaat ccgcagtaca acccagggga caaagatacc 1860aaaattgcca agaggatggc tgtgttgatc ttcaccgact tcatatgcat ggccccaatc 1920tcattctatg ctctgtcagc aattctgaac aagcctctca tcactgttag caactccaaa 1980atcttgctgg tactcttcta tccacttaac tcctacgcca atccattcct ctatgctatt 2040ttcaccaagg ccttccagag ggatgtgttc atcctactca gcaagtttgg catctgtaaa 2100cgccaggctc aggcataccg ggggcagagg gttcctccaa agaacagcac tgatattcag 2160gttcaaaagg ttacccacga gatgaggcag ggtctccaca acatggaaga tgtctatgaa 2220ctgattgaaa agtcccatct aaccccaaag aagcaaggcc aaatctcaga agagtatatg 2280caaacggttt tg 2292<210>419<211>764<212>PRT<213>智人(Homo sapiens)<400>419Met Arg Pro Ala Asp Leu Leu Gln Leu Val Leu Leu Leu Asp Leu Pro1 5 10 15Arg Asp Leu Gly Gly Met Gly Cys Ser Ser Pro Pro Cys Glu Cys His
20 25 30Gln Glu Glu Asp Phe Arg Val Thr Cys Lys Asp Ile Gln Arg Ile Pro
35 40 45Ser Leu Pro Pro Ser Thr Gln Thr Leu Lys Leu Ile Glu Thr His Leu
50 55 60Arg Thr Ile Pro Ser His Ala Phe Ser Asn Leu Pro Asn Ile Ser Arg65 70 75 80Ile Tyr Val Ser Ile Asp Val Thr Leu Gln Gln Leu Glu Ser His Ser
85 90 95Phe Tyr Asn Leu Ser Lys Val Thr His Ile Glu Ile Arg Asn Thr Arg
100 105 110Asn Leu Thr Tyr Ile Asp Pro Asp Ala Leu Lys Glu Leu Pro Leu Leu
115 120 125Lys Phe Leu Gly Ile Phe Asn Thr Gly Leu Lys Met Phe Pro Asp Leu
130 135 140Thr Lys Val Tyr Ser Thr Asp Ile Phe Phe Ile Leu Glu Ile Thr Asp145 150 155 160Asn Pro Tyr Met Thr Ser Ile Pro Val Asn Ala Phe Gln Gly Leu Cys
165 170 175Asn Glu Thr Leu Thr Leu Lys Leu Tyr Asn Asn Gly Phe Thr Ser Val
180 185 190Gln Gly Tyr Ala Phe Asn Gly Thr Lys Leu Asp Ala Val Tyr Leu Asn
195 200 205Lys Asn Lys Tyr Leu Thr Val Ile Asp Lys Asp Ala Phe Gly Gly Val
210 215 220Tyr Ser Gly Pro Ser Leu Leu Asp Val Ser Gln Thr Ser Val Thr Ala225 230 235 240Leu Pro Ser Lys Gly Leu Glu His Leu Lys Glu Leu Ile Ala Arg Asn
245 250 255Thr Trp Thr Leu Lys Lys Leu Pro Leu Ser Leu Ser Phe Leu His Leu
260 265 270Thr Arg Ala Asp Leu Ser Tyr Pro Ser His Cys Cys Ala Phe Lys Asn
275 280 285Gln Lys Lys Ile Arg Gly Ile Leu Glu Ser Leu Met Cys Asn Glu Ser
290 295 300Ser Met Gln Ser Leu Arg Gln Arg Lys Ser Val Asn Ala Leu Asn Ser305 310 315 320Pro Leu His Gln Glu Tyr Glu Glu Asn Leu Gly Asp Ser Ile Val Gly
325 330 335Tyr Lys Glu Lys Ser Lys Phe Gln Asp Thr His Asn Asn Ala His Tyr
340 345 350Tyr Val Phe Phe Glu Glu Gln Glu Asp Glu Ile Ile Gly Phe Gly Gln
355 360 365Glu Leu Lys Asn Pro Gln Glu Glu Thr Leu Gln Ala Phe Asp Ser His
370 375 380Tyr Asp Tyr Thr Ile Cys Gly Asp Ser Glu Asp Met Val Cys Thr Pro385 390 395 400Lys Ser Asp Glu Phe Asn Pro Cys Glu Asp Ile Met Gly Tyr Lys Phe
405 410 415Leu Arg Ile Val Val Trp Phe Val Ser Leu Leu Ala Leu Leu Gly Asn
420 425 430Val Phe Val Leu Leu Ile Leu Leu Thr Ser His Tyr Lys Leu Asn Val
435 440 445Pro Arg Phe Leu Met Cys Asn Leu Ala Phe Ala Asp Phe Cys Met Gly
450 455 460Met Tyr Leu Leu Leu Ile Ala Ser Val Asp Leu Tyr Thr His Ser Glu465 470 475 480Tyr Tyr Asn His Ala Ile Asp Trp Gln Thr Gly Pro Gly Cys Asn Thr
485 490 495Ala Gly Phe Phe Thr Val Phe Ala Ser Glu Leu Ser Ala Tyr Thr Leu
500 505 510Thr Val Ile Thr Leu Glu Arg Trp Tyr Ala Ile Thr Phe Ala Met Arg
515 520 525Leu Asp Arg Lys Ile Arg Leu Arg His Ala Cys Ala Ile Met Val Gly
530 535 540Gly Trp Val Cys Cys Phe Leu Leu Ala Leu Leu Pro Leu Val Gly Ile545 550 555 560Ser Ser Tyr Ala Lys Val Ser Ile Cys Leu Pro Met Asp Thr Glu Thr
565 570 575Pro Leu Ala Leu Ala Tyr Ile Val Phe Val Leu Thr Leu Asn Ile Val
580 585 590Ala Phe Val Ile Val Cys Cys Cys Tyr Val Lys Ile Tyr Ile Thr Val
595 600 605Arg Asn Pro Gln Tyr Asn Pro Gly Asp Lys Asp Thr Lys Ile Ala Lys
610 615 620Arg Met Ala Val Leu Ile Phe Thr Asp Phe Ile Cys Met Ala Pro Ile625 630 635 640Ser Phe Tyr Ala Leu Ser Ala Ile Leu Asn Lys Pro Leu Ile Thr Val
645 650 655Ser Asn Ser Lys Ile Leu Leu Val Leu Phe Tyr Pro Leu Asn Ser Tyr
660 665 670Ala Asn Pro Phe Leu Tyr Ala Ile Phe Thr Lys Ala Phe Gln Arg Asp
675 680 685Val Phe Ile Leu Leu Ser Lys Phe Gly Ile Cys Lys Arg Gln Ala Gln
690 695 700Ala Tyr Arg Gly Gln Arg Val Pro Pro Lys Asn Ser Thr Asp Ile Gln705 710 715 720Val Gln Lys Val Thr His Glu Met Arg Gln Gly Leu His Asn Met Glu
725 730 735Asp Val Tyr Glu Leu Ile Glu Lys Ser His Leu Thr Pro Lys Lys Gln
740 745 750Gly Gln Ile Ser Glu Glu Tyr Met Gln Thr Val Leu
755 760<210>420<211>33<212>DNA<213>智人(Homo sapiens)<400>420aaagatacca aaat taagaa gaggatggct gtg 33<210>421<211>33<212>DNA<213>智人(Homo sapiens)<400>421cacagccatc ctcttcttaa ttttggtatc ttt 33<210>422<211>2292<212>DNA<213>智人(Homo sapiens)<400>422atgaggccgg cggacttgct gcagctggtg ctgctgctcg acctgcccag ggacctgggc 60ggaatggggt gttcgtctcc accctgcgag tgccatcagg aggaggactt cagagtcacc 120tgcaaggata ttcaacgcat ccccagctta ccgcccagta cgcagactct gaagcttatt 180gagactcacc tgagaactat tccaagtcat gcattttcta atctgcccaa tatttccaga 240atctacgtat ctatagatgt gactctgcag cagctggaat cacactcctt ctacaatttg 300agtaaagtga ctcacataga aattcggaat accaggaact taacttacat agaccctgat 360gccctcaaag agctccccct cctaaagttc cttggcattt tcaacactgg acttaaaatg 420ttccctgacc tgaccaaagt ttattccact gatatattct ttatacttga aattacagac 480aacccttaca tgacgtcaat ccctgtgaat gcttttcagg gactatgcaa tgaaaccttg 540acactgaagc tgtacaacaa cggctttact tcagtccaag gatatgcttt caatgggaca 600aagctggatg ctgtttacct aaacaagaat aaatacctga cagttattga caaagatgca 660tttggaggag tatacagtgg accaagcttg ctggacgtgt ctcaaaccag tgtcactgcc 720cttccatcca aaggcctgga gcacctgaag gaactgatag caagaaacac ctggactctt 780aagaaacttc cactttcctt gagtttcctt cacctcacac gggctgacct ttcttaccca 840agccactgct gtgcctttaa gaatcagaag aaaatcagag gaatccttga gtccttgatg 900tgtaatgaga gcagtatgca gagcttgcgc cagagaaaat ctgtgaatgc cttgaatagc 960cccctccacc aggaatatga agagaatctg ggtgacagca ttgttgggta caaggaaaag 1020tccaagttcc aggatactca taacaacgct cattattacg tcttctttga agaacaagag 1080gatgagatca ttggttttgg ccaggagctc aaaaaccccc aggaagagac tctacaagct 1140tttgacagcc attatgacta caccatatgt ggggacagtg aagacatggt gtgtaccccc 1200aagtccgatg agttcaaccc gtgtgaagac ataatgggct acaagttcct gagaattgtg 1260gtgtggttcg ttagtctgct ggctctcctg ggcaatgtct ttgtcctgct tattctcctc 1320accagccact acaaactgaa cgtcccccgc tttctcatgt gcaacctggc ctttgcggat 1380ttctgcatgg ggatgtacct gctcctcatc gcctctgtag acctctacac tcactctgag 1440tactacaacc atgccatcga ctggcagaca ggccctgggt gcaacacggc tggtttcttc 1500actgtctttg caagcgagtt atcggtgcat acgctgacgg tcatcaccct ggagcgctgg 1560tatgccatca ccttcgccat gcgcctggac cggaagatcc gcctcaggca cgcatgtgcc 1620atcatggttg ggggctgggt ttgctgcttc cttctcgccc tgcttccttt ggtgggaata 1680agtagctatg ccaaagtcag tatctgcctg cccatggaca ccgagacccc tcttgctctg 1740gcatatattg tttttgttct gacgctcaac atagttgcct tcgtcatcgt ctgctgctgt 1800tatgtgaaga tctacatcac agtccgaaat ccgcagtaca acccagggga caaagatacc 1860aaaattaaga agaggatggc tgtgttgatc ttcaccgact tcatatgcat ggccccaatc 1920tcattctatg ctctgtcagc aattctgaac aagcctctca tcactgttag caactccaaa 1980atcttgctgg tactcttcta tccacttaac tcctacgcca atccattcct ctatgctatt 2040ttcaccaagg ccttccagag ggatgtgttc atcctactca gcaagtttgg catctgtaaa 2100cgccaggctc aggcataccg ggggcagagg gttcctccaa agaacagcac tgatattcag 2160gttcaaaagg ttacccacga gatgaggcag ggtctccaca acatggaaga tgtctatgaa 2220ctgattgaaa agtcccatct aaccccaaag aagcaaggcc aaatctcaga agagtatatg 2280caaacggttt tg 2292<210>423<211>764<212>PRT<213>智人(Homo sapiens)<400>423Met Arg Pro Ala Asp Leu Leu Gln Leu Val Leu Leu Leu Asp Leu Pro1 5 10 15Arg Asp Leu Gly Gly Met Gly Cys Ser Ser Pro Pro Cys Glu Cys His
20 25 30Gln Glu Glu Asp Phe Arg Val Thr Cys Lys Asp Ile Gln Arg Ile Pro
35 40 45Ser Leu Pro Pro Ser Thr Gln Thr Leu Lys Leu Ile Glu Thr His Leu
50 55 60Arg Thr Ile Pro Ser His Ala Phe Ser Asn Leu Pro Asn Ile Ser Arg65 70 75 80Ile Tyr Val Ser Ile Asp Val Thr Leu Gln Gln Leu Glu Ser His Ser
85 90 95Phe Tyr Asn Leu Ser Lys Val Thr His Ile Glu Ile Arg Asn Thr Arg
100 105 110Asn Leu Thr Tyr Ile Asp Pro Asp Ala Leu Lys Glu Leu Pro Leu Leu
115 120 125Lys Phe Leu Gly Ile Phe Asn Thr Gly Leu Lys Met Phe Pro Asp Leu
130 135 140Thr Lys Val Tyr Ser Thr Asp Ile Phe Phe Ile Leu Glu Ile Thr Asp145 150 155 160Asn Pro Tyr Met Thr Ser Ile Pro Val Asn Ala Phe Gln Gly Leu Cys
165 170 175Asn Glu Thr Leu Thr Leu Lys Leu Tyr Asn Asn Gly Phe Thr Ser Val
180 185 190Gln Gly Tyr Ala Phe Asn Gly Thr Lys Leu Asp Ala Val Tyr Leu Asn
195 200 205Lys Asn Lys Tyr Leu Thr Val Ile Asp Lys Asp Ala Phe Gly Gly Val
210 215 220Tyr Ser Gly Pro Ser Leu Leu Asp Val Ser Gln Thr Ser Val Thr Ala225 230 235 240Leu Pro Ser Lys Gly Leu Glu His Leu Lys Glu Leu Ile Ala Arg Asn
245 250 255Thr Trp Thr Leu Lys Lys Leu Pro Leu Ser Leu Ser Phe Leu His Leu
260 265 270Thr Arg Ala Asp Leu Ser Tyr Pro Ser His Cys Cys Ala Phe Lys Asn
275 280 285Gln Lys Lys Ile Arg Gly Ile Leu Glu Ser Leu Met Cys Asn Glu Ser
290 295 300Ser Met Gln Ser Leu Arg Gln Arg Lys Ser Val Asn Ala Leu Asn Ser305 310 315 320Pro Leu His Gln Glu Tyr Glu Glu Asn Leu Gly Asp Ser Ile Val Gly
325 330 335Tyr Lys Glu Lys Ser Lys Phe Gln Asp Thr His Asn Asn Ala His Tyr
340 345 350Tyr Val Phe Phe Glu Glu Gln Glu Asp Glu Ile Ile Gly Phe Gly Gln
355 360 365Glu Leu Lys Asn Pro Gln Glu Glu Thr Leu Gln Ala Phe Asp Ser His
370 375 380Tyr Asp Tyr Thr Ile Cys Gly Asp Ser Glu Asp Met Val Cys Thr Pro385 390 395 400Lys Ser Asp Glu Phe Asn Pro Cys Glu Asp Ile Met Gly Tyr Lys Phe
405 410 415Leu Arg Ile Val Val Trp Phe Val Ser Leu Leu Ala Leu Leu Gly Asn
420 425 430Val Phe Val Leu Leu Ile Leu Leu Thr Ser His Tyr Lys Leu Asn Val
435 440 445Pro Arg Phe Leu Met Cys Asn Leu Ala Phe Ala Asp Phe Cys Met Gly
450 455 460Met Tyr Leu Leu Leu Ile Ala Ser Val Asp Leu Tyr Thr His Ser Glu465 470 475 480Tyr Tyr Asn His Ala Ile Asp Trp Gln Thr Gly Pro Gly Cys Asn Thr
485 490 495Ala Gly Phe Phe Thr Val Phe Ala Ser Glu Leu Ser Ala Tyr Thr Leu
500 505 510Thr Val Ile Thr Leu Glu Arg Trp Tyr Ala Ile Thr Phe Ala Met Arg
515 520 525Leu Asp Arg Lys Ile Arg Leu Arg His Ala Cys Ala Ile Met Val Gly
530 535 540Gly Trp Val Cys Cys Phe Leu Leu Ala Leu Leu Pro Leu Val Gly Ile545 550 555 560Ser Ser Tyr Ala Lys Val Ser Ile Cys Leu Pro Met Asp Thr Glu Thr
565 570 575Pro Leu Ala Leu Ala Tyr Ile Val Phe Val Leu Thr Leu Asn Ile Val
580 585 590Ala Phe Val Ile Val Cys Cys Cys Tyr Val Lys Ile Tyr Ile Thr Val
595 600 605Arg Asn Pro Gln Tyr Asn Pro Gly Asp Lys Asp Thr Lys Ile Lys Lys
610 615 620Arg Met Ala Val Leu Ile Phe Thr Asp Phe Ile Cys Met Ala Pro Ile625 630 635 640Ser Phe Tyr Ala Leu Ser Ala Ile Leu Asn Lys Pro Leu Ile Thr Val
645 650 655Ser Asn Ser Lys Ile Leu Leu Val Leu Phe Tyr Pro Leu Asn Ser Tyr
660 665 670Ala Asn Pro Phe Leu Tyr Ala Ile Phe Thr Lys Ala Phe Gln Arg Asp
675 680 685Val Phe Ile Leu Leu Ser Lys Phe Gly Ile Cys Lys Arg Gln Ala Gln
690 695 700Ala Tyr Arg Gly Gln Arg Val Pro Pro Lys Asn Ser Thr Asp Ile Gln705 710 715 720Val Gln Lys Val Thr His Glu Met Arg Gln Gly Leu His Asn Met Glu
725 730 735Asp Val Tyr Glu Leu Ile Glu Lys Ser His Leu Thr Pro Lys Lys Gln
740 745 750Gly Gln Ile Ser Glu Glu Tyr Met Gln Thr Val Leu
755 760<210>424<211>1266<212>DNA<213>智人(Homo sapiens)<400>424atggatgtgc tcagccctgg tcagggcaac aacaccacat caccaccggc tccctttgag 60accggcggca acactactgg tatctccgac gtgaccgtca gctaccaagt gatcacctct 120ctgctgctgg gcacgctcat cttctgcgcg gtgctgggca atgcgtgcgt ggtggctgcc 180atcgccttgg agcgctccct gcagaacgtg gccaattatc ttattggctc tttggcggtc 240accgacctca tggtgtcggt gttggtgctg cccatggccg cgctgtatca ggtgctcaac 300aagtggacac tgggccaggt aacctgcgac ctgttcatcg ccctcgacgt gctgtgctgc 360acctcatcca tcttgcacct gtgcgccatc gcgctggaca ggtactgggc catcacggac 420cccatcgact acgtgaacaa gaggacgccc cggccgcgtg cgctcatctc gctcacttgg 480cttattggct tcctcatctc tatcccgccc atcctgggct ggcgcacccc ggaagaccgc 540tcggaccccg acgcatgcac cattagcaag gatcatggct acactatcta ttccaccttt 600ggagctttct acatcccgct gctgctcatg ctggttctct atgggcgcat attccgagct 660gcgcgcttcc gcatccgcaa gacggtcaaa aaggtggaga agaccggagc ggacacccgc 720catggagcat ctcccgcccc gcagcccaag aagagtgtga atggagagtc ggggagcagg 780aactggaggc tgggcgtgga gagcaaggct gggggtgctc tgtgcgccaa tggcgcggtg 840aggcaaggtg acgatggcgc cgccctggag gtgatcgagg tgcaccgagt gggcaactcc 900aaagagcact tgcctctgcc cagcgaggct ggtcctaccc cttgtgcccc cgcctctttc 960gagaggaaaa atgagcgcaa cgccgaggcg aagcgcaaga tggccctggc ccgagagagg 1020aagacaaaga agacgctggg catcatcatg ggcaccttca tcctctgctg gctgcccttc 1080ttcatcgtgg ctcttgttct gcccttctgc gagagcagct gccacatgcc caccctgttg 1140ggcgccataa tcaattggct gggctactcc aactctctgc ttaaccccgt catttacgca 1200tacttcaaca aggactttca aaacgcgttt aagaagatca ttaagtgtaa cttctgccgc 1260cagtga 1266<210>425<211>421<212>PRT<213>智人(Homo sapiens)<400>425Met Asp Val Leu Ser Pro Gly Gln Gly Asn Asn Thr Thr Ser Pro Pro1 5 10 15Ala Pro Phe Glu Thr Gly Gly Asn Thr Thr Gly Ile Ser Asp Val Thr
20 25 30Val Ser Tyr Gln Val Ile Thr Ser Leu Leu Leu Gly Thr Leu Ile Phe
35 40 45Cys Ala Val Leu Gly Asn Ala Cys Val Val Ala Ala Ile Ala Leu Glu
50 55 60Arg Ser Leu Gln Asn Val Ala Asn Tyr Leu Ile Gly Ser Leu Ala Val65 70 75 80Thr Asp Leu Met Val Ser Val Leu Val Leu Pro Met Ala Ala Leu Tyr
85 90 95Gln Val Leu Asn Lys Trp Thr Leu Gly Gln Val Thr Cys Asp Leu Phe
100 105 110Ile Ala Leu Asp Val Leu Cys Cys Thr Ser Ser Ile Leu His Leu Cys
115 120 125Ala Ile Ala Leu Asp Arg Tyr Trp Ala Ile Thr Asp Pro Ile Asp Tyr
130 135 140Val Asn Lys Arg Thr Pro Arg Pro Arg Ala Leu Ile Ser Leu Thr Trp145 150 155 160Leu Ile Gly Phe Leu Ile Ser Ile Pro Pro Ile Leu Gly Trp Arg Thr
165 170 175Pro Glu Asp Arg Ser Asp Pro Asp Ala Cys Thr Ile Ser Lys Asp His
180 185 190Gly Tyr Thr Ile Tyr Ser Thr Phe Gly Ala Phe Tyr Ile Pro Leu Leu
195 200 205Leu Met Leu Val Leu Tyr Gly Arg Ile Phe Arg Ala Ala Arg Phe Arg
210 215 220Ile Arg Lys Thr Val Lys Lys Val Glu Lys Thr Gly Ala Asp Thr Arg225 230 235 240His Gly Ala Ser Pro Ala Pro Gln Pro Lys Lys Ser Val Asn Gly Glu
245 250 255Ser Gly Ser Arg Asn Trp Arg Leu Gly Val Glu Ser Lys Ala Gly Gly
260 265 270Ala Leu Cys Ala Asn Gly Ala Val Arg Gln Gly Asp Asp Gly Ala Ala
275 280 285Leu Glu Val Ile Glu Val His Arg Val Gly Asn Ser Lys Glu His Leu
290 295 300Pro Leu Pro Ser Glu Ala Gly Pro Thr Pro Cys Ala Pro Ala Ser Phe305 310 315 320Glu Arg Lys Asn Glu Arg Asn Ala Glu Ala Lys Arg Lys Met Ala Leu
325 330 335Ala Arg Glu Arg Lys Thr Lys Lys Thr Leu Gly Ile Ile Met Gly Thr
340 345 350Phe Ile Leu Cys Trp Leu Pro Phe Phe Ile Val Ala Leu Val Leu Pro
355 360 365Phe Cys Glu Ser Ser Cys His Met Pro Thr Leu Leu Gly Ala Ile Ile
370 375 380Asn Trp Leu Gly Tyr Ser Asn Ser Leu Leu Asn Pro Val Ile Tyr Ala385 390 395 400Tyr Phe Asn Lys Asp Phe Gln Asn Ala Phe Lys Lys Ile Ile Lys Cys
405 410 415Asn Phe Cys Arg Gln
420<210>426<211>1173<212>DNA<213>智人(Homo sapiens)<400>426atggaggaac cgggtgctca gtgcgctcca ccgccgcccg cgggctccga gacctgggtt 60cctcaagcca acttatcctc tgctccctcc caaaactgca gcgccaagga ctacatttac 120caggactcca tctccctacc ctggaaagta ctgctggtta tgctattggc gctcatcacc 180ttggccacca cgctctccaa tgcctttgtg attgccacag tgtaccggac ccggaaactg 240cacaccccgg ctaactacct gatcgcctct ctggcagtca ccgacctgct tgtgtccatc 300ctggtgatgc ccatcagcac catgtacact gtcaccggcc gctggacact gggccaggtg 360gtctgtgact tctggctgtc gtcggacatc acttgttgca ctgcctccat cctgcacctc 420tgtgtcatcg ccctggaccg ctactgggcc atcacggacg ccgtggagta ctcagctaaa 480aggactccca agagggcggc ggtcatgatc gcgctggtgt gggtcttctc catctctatc 540tcgctgccgc ccttcttctg gcgtcaggct aaggccgaag aggaggtgtc ggaatgcgtg 600gtgaacaccg accacatcct ctacacggtc tactccacgg tgggtgcttt ctacttcccc 660accctgctcc tcatcgccct ctatggccgc atctacgtag aagcccgctc ccggattttg 720aaacagacgc ccaacaggac cggcaagcgc ttgacccgag cccagctgat aaccgactcc 780cccgggtcca cgtcctcggt cacctctatt aactcgcggg ttcccgacgt gcccagcgaa 840tccggatctc ctgtgtatgt gaaccaagtc aaagtgcgag tctccgacgc cctgctggaa 900aagaagaaac tcatggccgc tagggagcgc aaagccaaga agaccctagg gatcattttg 960ggagccttta ttgtgtgttg gctacccttc ttcatcatct ccctagtgat gcctatctgc 1020aaagatgcct gctggttcca cctagccatc tttgacttct tcacatggct gggctatctc 1080aactccctca tcaaccccat aatctatacc atgtccaatg aggactttaa acaagcattc 1140cataaactga tacgttttaa gtgcacaagt tga 1173<210>427<211>390<212>PRT<213>智人(Homo sapiens)<400>427Met Glu Glu Pro Gly Ala Gln Cys Ala Pro Pro Pro Pro Ala Gly Ser1 5 10 15Glu Thr Trp Val Pro Gln Ala Asn Leu Ser Ser Ala Pro Ser Gln Asn
20 25 30Cys Ser Ala Lys Asp Tyr Ile Tyr Gln Asp Ser Ile Ser Leu Pro Trp
35 40 45Lys Val Leu Leu Val Met Leu Leu Ala Leu Ile Thr Leu Ala Thr Thr
50 55 60Leu Ser Asn Ala Phe Val Ile Ala Thr Val Tyr Arg Thr Arg Lys Leu65 70 75 80His Thr Pro Ala Asn Tyr Leu Ile Ala Ser Leu Ala Val Thr Asp Leu
85 90 95Leu Val Ser Ile Leu Val Met Pro Ile Ser Thr Met Tyr Thr Val Thr
100 105 110Gly Arg Trp Thr Leu Gly Gln Val Val Cys Asp Phe Trp Leu Ser Ser
115 120 125Asp Ile Thr Cys Cys Thr Ala Ser Ile Leu His Leu Cys Val Ile Ala
130 135 140Leu Asp Arg Tyr Trp Ala Ile Thr Asp Ala Val Glu Tyr Ser Ala Lys145 150 155 160Arg Thr Pro Lys Arg Ala Ala Val Met Ile Ala Leu Val Trp Val Phe
165 170 175Ser Ile Ser Ile Ser Leu Pro Pro Phe Phe Trp Arg Gln Ala Lys Ala
180 185 190Glu Glu Glu Val Ser Glu Cys Val Val Asn Thr Asp His Ile Leu Tyr
195 200 205Thr Val Tyr Ser Thr Val Gly Ala Phe Tyr Phe Pro Thr Leu Leu Leu
210 215 220Ile Ala Leu Tyr Gly Arg Ile Tyr Val Glu Ala Arg Ser Arg Ile Leu225 230 235 240Lys Gln Thr Pro Asn Arg Thr Gly Lys Arg Leu Thr Arg Ala Gln Leu
245 250 255Ile Thr Asp Ser Pro Gly Ser Thr Ser Ser Val Thr Ser Ile Asn Ser
260 265 270Arg Val Pro Asp Val Pro Ser Glu Ser Gly Ser Pro Val Tyr Val Asn
275 280 285Gln Val Lys Val Arg Val Ser Asp Ala Leu Leu Glu Lys Lys Lys Leu
290 295 300Met Ala Ala Arg Glu Arg Lys Ala Lys Lys Thr Leu Gly Ile Ile Leu305 310 315 320Gly Ala Phe Ile Val Cys Trp Leu Pro Phe Phe Ile Ile Ser Leu Val
325 330 335Met Pro Ile Cys Lys Asp Ala Cys Trp Phe His Leu Ala Ile Phe Asp
340 345 350Phe Phe Thr Trp Leu Gly Tyr Leu Asn Ser Leu Ile Asn Pro Ile Ile
355 360 365Tyr Thr Met Ser Asn Glu Asp Phe Lys Gln Ala Phe His Lys Leu Ile
370 375 380Arg Phe Lys Cys Thr Ser385 390<210>428<211>1134<212>DNA<213>智人(Homo sapiens)<400>428atgtccccac tgaaccagtc agcagaaggc cttccccagg aggcctccaa cagatccctg 60aatgccacag aaacctcaga ggcttgggat cccaggaccc tccaggcgct caagatctcc 120cttgccgtgg tcctttccgt catcacactg gccacagtcc tctccaatgc ctttgtactc 180accaccatct tactcaccag gaagctccac acccctgcca actacctgat tggctccctg 240gccaccaccg acctcttggt ttccatcttg gtaatgccca tcagcatcgc ctataccatc 300acccacacct ggaactttgg ccaaatcttg tgtgacatct ggctgtcctc tgacatcacg 360tgctgcacag cctccatcct gcatctctgt gtcattgctc tggacaggta ctgggcaatc 420acagatgccc tggaatacag taaacgcagg acggctggcc acgcggccac catgatcgcc 480attgtctggg ccatctccat ctgcatctcc atccccccgc tcttctggcg gcaggccaag 540gcccaggagg agatgtcgga ctgtctggtg aacacctctc agatctccta caccatctac 600tccacctgtg gggccttcta cattccctcg gtgttgctca tcatcctata tggccggatc 660taccgggctg cccggaaccg catcctgaat ccaccctcac tctatgggaa gcgcttcacc 720acggcccacc tcatcacagg ctctgccggg tcctcgctct gctcgctcaa ctccagcctc 780catgaggggc actcgcactc ggctggctcc cctctctttt tcaaccacgt gaaaatcaag 840cttgctgaca gtgccctgga acgcaagagg atttctgctg ctcgagaaag gaaagccaag 900aaaatcctgg gcatcattct gggggccttt atcatctgct ggctgccctt cttcgtggtg 960tctctggtcc tccccatctg ccgggactcc tgctggatcc acccggcgct ctttgacttc 1020ttcacctggc taggctattt aaactccctc atcaatccaa taatctacac tgtgtttaat 1080gaagagtttc ggcaagcttt tcagaaaatt gtccctttcc ggaaggcctc ctag 1134<210>429<211>377<212>PRT<213>智人(Homo sapiens)<400>429Met Ser Pro Leu Asn Gln Ser Ala Glu Gly Leu Pro Gln Glu Ala Ser1 5 10 15Asn Arg Ser Leu Asn Ala Thr Glu Thr Ser Glu Ala Trp Asp Pro Arg
20 25 30Thr Leu Gln Ala Leu Lys Ile Ser Leu Ala Val Val Leu Ser Val Ile
35 40 45Thr Leu Ala Thr Val Leu Ser Asn Ala Phe Val Leu Thr Thr Ile Leu
50 55 60Leu Thr Arg Lys Leu His Thr Pro Ala Asn Tyr Leu Ile Gly Ser Leu65 70 75 80Ala Thr Thr Asp Leu Leu Val Ser Ile Leu Val Met Pro Ile Ser Ile
85 90 95Ala Tyr Thr Ile Thr His Thr Trp Asn Phe Gly Gln Ile Leu Cys Asp
100 105 110Ile Trp Leu Ser Ser Asp Ile Thr Cys Cys Thr Ala Ser Ile Leu His
115 120 125Leu Cys Val Ile Ala Leu Asp Arg Tyr Trp Ala Ile Thr Asp Ala Leu
130 135 140Glu Tyr Ser Lys Arg Arg Thr Ala Gly His Ala Ala Thr Met Ile Ala145 150 155 160Ile Val Trp Ala Ile Ser Ile Cys Ile Ser Ile Pro Pro Leu Phe Trp
165 170 175Arg Gln Ala Lys Ala Gln Glu Glu Met Ser Asp Cys Leu Val Asn Thr
180 185 190Ser Gln Ile Ser Tyr Thr Ile Tyr Ser Thr Cys Gly Ala Phe Tyr Ile
195 200 205Pro Ser Val Leu Leu Ile Ile Leu Tyr Gly Arg Ile Tyr Arg Ala Ala
210 215 220Arg Asn Arg Ile Leu Asn Pro Pro Ser Leu Tyr Gly Lys Arg Phe Thr225 230 235 240Thr Ala His Leu Ile Thr Gly Ser Ala Gly Ser Ser Leu Cys Ser Leu
245 250 255Asn Ser Ser Leu His Glu Gly His Ser His Ser Ala Gly Ser Pro Leu
260 265 270Phe Phe Asn His Val Lys Ile Lys Leu Ala Asp Ser Ala Leu Glu Arg
275 280 285Lys Arg Ile Ser Ala Ala Arg Glu Arg Lys Ala Lys Lys Ile Leu Gly
290 295 300Ile Ile Leu Gly Ala Phe Ile Ile Cys Trp Leu Pro Phe Phe Val Val305 310 315 320Ser Leu Val Leu Pro Ile Cys Arg Asp Ser Cys Trp Ile His Pro Ala
325 330 335Leu Phe Asp Phe Phe Thr Trp Leu Gly Tyr Leu Asn Ser Leu Ile Asn
340 345 350Pro Ile Ile Tyr Thr Val Phe Asn Glu Glu Phe Arg Gln Ala Phe Gln
355 360 365Lys Ile Val Pro Phe Arg Lys Ala Ser
370 375<210>430<211>1098<212>DNA<213>智人(Homo sapiens)<400>430atgaacatca caaactgtac cacagaggcc agcatggcta taagacccaa gaccatcact 60gagaagatgc tcatttgcat gactctggtg gtcatcacca ccctcaccac gttgctgaac 120ttggctgtga tcatggctat tggcaccacc aagaagctcc accagcctgc caactaccta 180atctgttctc tggccgtgac ggacctcctg gtggcagtgc tcgtcatgcc cctgagcatc 240atctacattg tcatggatcg ctggaagctt gggtacttcc tctgtgaggt gtggctgagt 300gtggacatga cctgctgcac ctgctccatc ctccacctct gtgtcattgc cctggacagg 360tactgggcca tcaccaatgc tattgaatac gccaggaaga ggacggccaa gagggccgcg 420ctgatgatcc ttaccgtctg gaccatctcc attttcatct ccatgccccc tctgttctgg 480agaagccacc gccgcctaag ccctccccct agtcagtgca ccatccagca cgaccatgtt 540atctacacca tttactccac gctgggtgcg ttttatatcc ccttgacttt gatactgatt 600ctctattacc ggatttacca cgcggccaag agcctttacc agaaaagggg atcaagtcgg 660cacttaagca acagaagcac agatagccag aattcttttg caagttgtaa acttacacag 720actttctgtg tgtctgactt ctccacctca gaccctacca cagagtttga aaagttccat 780gcctccatca ggatcccccc cttcgacaat gatctagatc acccaggaga acgtcagcag 840atctctagca ccagggaacg gaaggcaaaa cgcatcctgg ggctgattct gggtgcattc 900attttatcct ggctgccatt tttcatcaaa gagttgattg tgggtctgag catctacacc 960gtgtcctcgg aagtggccga ctttctgacg tggctcggtt atgtgaattc tctgatcaac 1020cctctgctct atacgagttt taatgaagac tttaagctgg cttttaaaaa gctcattaga 1080tgccgagagc atacttag 1098<210>431<211>365<212>PRT<213>智人(Homo sapiens)<400>43lMet Asn Ile Thr Asn Cys Thr Thr Glu Ala Ser Met Ala Ile Arg Prol 5 10 15Lys Thr Ile Thr Glu Lys Met Leu Ile Cys Met Thr Leu Val Val Ile
20 25 30Thr Thr Leu Thr Thr Leu Leu Asn Leu Ala Val Ile Met Ala Ile Gly
35 40 45Thr Thr Lys Lys Leu His Gln Pro Ala Asn Tyr Leu Ile Cys Ser Leu
50 55 60Ala Val Thr Asp Leu Leu Val Ala Val Leu Val Met Pro Leu Ser Ile65 70 75 80Ile Tyr Ile Val Met Asp Arg Trp Lys Leu Gly Tyr Phe Leu Cys Glu
85 90 95Val Trp Leu Ser Val Asp Met Thr Cys Cys Thr Cys Ser Ile Leu His
100 105 110Leu Cys Val Ile Ala Leu Asp Arg Tyr Trp Ala Ile Thr Asn Ala Ile
115 120 125Glu Tyr Ala Arg Lys Arg Thr Ala Lys Arg Ala Ala Leu Met Ile Leu
130 135 140Thr Val Trp Thr Ile Ser Ile Phe Ile Ser Met Pro Pro Leu Phe Trp145 150 155 160Arg Ser His Arg Arg Leu Ser Pro Pro Pro Ser Gln Cys Thr Ile Gln
165 170 175His Asp His Val Ile Tyr Thr Ile Tyr Ser Thr Leu Gly Ala Phe Tyr
180 185 190Ile Pro Leu Thr Leu Ile Leu Ile Leu Tyr Tyr Arg Ile Tyr His Ala
195 200 205Ala Lys Ser Leu Tyr Gln Lys Arg Gly Ser Ser Arg His Leu Ser Asn
210 215 220Arg Ser Thr Asp Ser Gln Asn Ser Phe Ala Ser Cys Lys Leu Thr Gln225 230 235 240Thr Phe Cys Val Ser Asp Phe Ser Thr Ser Asp Pro Thr Thr Glu Phe
245 250 255Glu Lys Phe His Ala Ser Ile Arg Ile Pro Pro Phe Asp Asn Asp Leu
260 265 270Asp His Pro Gly Glu Arg Gln Gln Ile Ser Ser Thr Arg Glu Arg Lys
275 280 285Ala Lys Arg Ile Leu Gly Leu Ile Leu Gly Ala Phe Ile Leu Ser Trp
290 295 300Leu Pro Phe Phe Ile Lys Glu Leu Ile Val Gly Leu Ser Ile Tyr Thr305 310 315 320Val Ser Ser Glu Val Ala Asp Phe Leu Thr Trp Leu Gly Tyr Val Asn
325 330 335Ser Leu Ile Asn Pro Leu Leu Tyr Thr Ser Phe Asn Glu Asp Phe Lys
340 345 350Leu Ala Phe Lys Lys Leu Ile Arg Cys Arg Glu His Thr
355 360 365<210>432<211>1101<212>DNA<213>智人(Homo sapiens)<400>432atggatttct taaattcatc tgatcaaaac ttgacctcag aggaactgtt aaacagaatg 60ccatccaaaa ttctggtgtc cctcactctg tctgggctgg cactgatgac aacaactatc 120aactcccttg tgatcgctgc aattattgtg acccggaagc tgcaccatcc agccaattat 180ttaatttgtt cccttgcagt cacagatttt cttgtggctg tcctggtgat gcccttcagc 240attgtgtata ttgtgagaga gagctggatt atggggcaag tggtctgtga catttggctg 300agtgttgaca ttacctgctg cacgtgctcc atcttgcatc tctcagctat agctttggat 360cggtatcgag caatcacaga tgctgttgag tatgccagga aaaggactcc aaagcatgct 420ggcattatga ttacaatagt ttggattata tctgttttta tctctatgcc tcctctattc 480tggaggcacc aaggaactag cagagatgat gaatgcatca tcaagcacga ccacattgtt 540tccaccattt actcaacatt tggagctttc tacatcccac tggcattgat tttgatcctt 600tactacaaaa tatatagagc agcaaagaca ttataccaca agagacaagc aagtaggatt 660gcaaaggagg aggtgaatgg ccaagtcctt ttggagagtg gtgagaaaag cactaaatca 720gtttccacat cctatgtact agaaaagtct ttatctgacc catcaacaga ctttgataaa 780attcatagca cagtgagaag tctcaggtct gaattcaagc atgagaaatc ttggagaagg 840caaaagatct caggtacaag agaacggaaa gcaaagacta ccctgggatt aatcttgggt 900gcatttgtaa tatgttggct tccttttttt gtaaaagaat tagttgttaa tgtctgtgac 960aaatgtaaaa tttctgaaga aatgtccaat tttttggcat ggcttgggta tctcaattcc 1020cttataaatc cactgattta cacaatcttt aatgaagact tcaagaaagc attccaaaag 1080cttgtgcgat gtcgatgtta g 1101<210>433<211>366<212>PRT<213>智人(Homo sapiens)<400>433Met Asp Phe Leu Asn Ser Ser Asp Gln Asn Leu Thr Ser Glu Glu Leu1 5 10 15Leu Asn Arg Met Pro Ser Lys Ile Leu Val Ser Leu Thr Leu Ser Gly
20 25 30Leu Ala Leu Met Thr Thr Thr Ile Asn Ser Leu Val Ile Ala Ala Ile
35 40 45Ile Val Thr Arg Lys Leu His His Pro Ala Asn Tyr Leu Ile Cys Ser
50 55 60Leu Ala Val Thr Asp Phe Leu Val Ala Val Leu Val Met Pro Phe Ser65 70 75 80Ile Val Tyr Ile Val Arg Glu Ser Trp Ile Met Gly Gln Val Val Cys
85 90 95Asp Ile Trp Leu Ser Val Asp Ile Thr Cys Cys Thr Cys Ser Ile Leu
100 105 110His Leu Ser Ala Ile Ala Leu Asp Arg Tyr Arg Ala Ile Thr Asp Ala
115 120 125Val Glu Tyr Ala Arg Lys Arg Thr Pro Lys His Ala Gly Ile Met Ile
130 135 140Thr Ile Val Trp Ile Ile Ser Val Phe Ile Ser Met Pro Pro Leu Phe145 150 155 160Trp Arg His Gln Gly Thr Ser Arg Asp Asp Glu Cys Ile Ile Lys His
165 170 175Asp His Ile Val Ser Thr Ile Tyr Ser Thr Phe Gly Ala Phe Tyr Ile
180 185 190Pro Leu Ala Leu Ile Leu Ile Leu Tyr Tyr Lys Ile Tyr Arg Ala Ala
195 200 205Lys Thr Leu Tyr His Lys Arg Gln Ala Ser Arg Ile Ala Lys Glu Glu
210 215 220Val Asn Gly Gln Val Leu Leu Glu Ser Gly Glu Lys Ser Thr Lys Ser225 230 235 240Val Ser Thr Ser Tyr Val Leu Glu Lys Ser Leu Ser Asp Pro Ser Thr
245 250 255Asp Phe Asp Lys Ile His Ser Thr Val Arg Ser Leu Arg Ser Glu Phe
260 265 270Lys His Glu Lys Ser Trp Arg Arg Gln Lys Ile Ser Gly Thr Arg Glu
275 280 285Arg Lys Ala Lys Thr Thr Leu Gly Leu Ile Leu Gly Ala Phe Val Ile
290 295 300Cys Trp Leu Pro Phe Phe Val Lys Glu Leu Val Val Asn Val Cys Asp305 310 315 320Lys Cys Lys Ile Ser Glu Glu Met Ser Asn Phe Leu Ala Trp Leu Gly
325 330 335Tyr Leu Asn Ser Leu Ile Asn Pro Leu Ile Tyr Thr Ile Phe Asn Glu
340 345 350Asp Phe Lys Lys Ala Phe Gln Lys Leu Val Arg Cys Arg Cys
355 360 365<210>434<211>1446<212>DNA<213>智人(Homo sapiens)<400>434atggctctct cttacagagt gtctgaactt caaagcacaa ttcctgagca cattttgcag 60agcacctttg ttcacgttat ctcttctaac tggtctggat tacagacaga atcaatacca 120gaggaaatga aacagattgt tgaggaacag ggaaataaac tgcactgggc agctcttctg 180atactcatgg tgataatacc cacaattggt ggaaataccc ttgttattct ggctgtttca 240ctggagaaga agctgcagta tgctactaat tactttctaa tgtccttggc ggtggctgat 300ttgctggttg gattgtttgt gatgccaatt gccctcttga caataatgtt tgaggctatg 360tggcccctcc cacttgttct atgtcctgcc tggttatttc ttgacgttct cttttcaacc 420gcatccatca tgcatctctg tgccatttca gtggatcgtt acatagccat caaaaagcca 480atccaggcca atcaatataa ctcacgggct acagcattca tcaagattac agtggtgtgg 540ttaatttcaa taggcattgc cattecagtc cctattaaag ggatagagac tgatgtggac 600aacccaaaca atatcacttg tgtgctgaca aaggaacgtt ttggcgattt catgctcttt 660ggctcactgg ctgccttctt cacacctctt gcaattatga ttgtcaccta ctttctcact 720atccatgctt tacagaagaa ggcttactta gtcaaaaaca agccacctca acgcctaaca 780tggttgactg tgtctacagt tttccaaagg gatgaaacac cttgctcgtc accggaaaag 840gtggcaatgc tggatggttc tcgaaaggac aaggctctgc ccaactcagg tgatgaaaca 900cttatgcgaa gaacatccac aattgggaaa aagtcagtgc agaccatttc caacgaacag 960agagccaaaa aggtcctagg gattgtgttt ttcctctttt tgcttatgtg gtgtcccttc 1020tttattacaa atataacttt agttttatgt gattcctgta accaaactac tctccaaatg 1080ctcctggaga tatttgtgtg gataggctat gtttcctcag gagtgaatcc tttggtctac 1140accctcttca ataagacatt tcgggatgca tttggccgat atatcacctg caattaccgg 1200gccacaaagt cagtaaaaac tctcagaaaa cgctccagta agatctactt ccggaatcca 1260atggcagaga actctaagtt tttcaagaaa catggaattc gaaatgggat taaccctgcc 1320atgtaccaga gtccaatgag gctccgaagt tcaaccattc agtcttcatc aatcattcta 1380ctagatacgc ttctcctcac tgaaaatgaa ggtgacaaaa ctgaagagca agttagttat 1440gtatag 1446<210>435<211>481<212>PRT<213>智人(Homo sapiens)<400>435Met Ala Leu Ser Tyr Arg Val Ser Glu Leu Gln Ser Thr Ile Pro Glu1 5 10 15His Ile Leu Gln Ser Thr Phe Val His Val Ile Ser Ser Asn Trp Ser
20 25 30Gly Leu Gln Thr Glu Ser Ile Pro Glu Glu Met Lys Gln Ile Val Glu
35 40 45Glu Gln Gly Asn Lys Leu His Trp Ala Ala Leu Leu Ile Leu Met Val
50 55 60Ile Ile Pro Thr Ile Gly Gly Asn Thr Leu Val Ile Leu Ala Val Ser65 70 75 80Leu Glu Lys Lys Leu Gln Tyr Ala Thr Asn Tyr Phe Leu Met Ser Leu
85 90 95Ala Val Ala Asp Leu Leu Val Gly Leu Phe Val Met Pro Ile Ala Leu
100 105 110Leu Thr Ile Met Phe Glu Ala Met Trp Pro Leu Pro Leu Val Leu Cys
115 120 125Pro Ala Trp Leu Phe Leu Asp Val Leu Phe Ser Thr Ala Ser Ile Met
130 135 140His Leu Cys Ala Ile Ser Val Asp Arg Tyr Ile Ala Ile Lys Lys Pro145 150 155 160Ile Gln Ala Asn Gln Tyr Asn Ser Arg Ala Thr Ala Phe Ile Lys Ile
165 170 175Thr Val Val Trp Leu Ile Ser Ile Gly Ile Ala Ile Pro Val Pro Ile
180 185 190Lys Gly Ile Glu Thr Asp Val Asp Asn Pro Asn Asn Ile Thr Cys Val
195 200 205Leu Thr Lys Glu Arg Phe Gly Asp Phe Met Leu Phe Gly Ser Leu Ala
210 215 220Ala Phe Phe Thr Pro Leu Ala Ile Met Ile Val Thr Tyr Phe Leu Thr225 230 235 240Ile His Ala Leu Gln Lys Lys Ala Tyr Leu Val Lys Asn Lys Pro Pro
245 250 255Gln Arg Leu Thr Trp Leu Thr Val Ser Thr Val Phe Gln Arg Asp Glu
260 265 270Thr Pro Cys Ser Ser Pro Glu Lys Val Ala Met Leu Asp Gly Ser Arg
275 280 285Lys Asp Lys Ala Leu Pro Asn Ser Gly Asp Glu Thr Leu Met Arg Arg
290 295 300Thr Ser Thr Ile Gly Lys Lys Ser Val Gln Thr Ile Ser Asn Glu Gln305 310 315 320Arg Ala Lys Lys Val Leu Gly Ile Val Phe Phe Leu Phe Leu Leu Met
325 330 335Trp Cys Pro Phe Phe Ile Thr Asn Ile Thr Leu Val Leu Cys Asp Ser
340 345 350Cys Asn Gln Thr Thr Leu Gln Met Leu Leu Glu Ile Phe Val Trp Ile
355 360 365Gly Tyr Val Ser Ser Gly Val Asn Pro Leu Val Tyr Thr Leu Phe Asn
370 375 380Lys Thr Phe Arg Asp Ala Phe Gly Arg Tyr Ile Thr Cys Asn Tyr Arg385 390 395 400Ala Thr Lys Ser Val Lys Thr Leu Arg Lys Arg Ser Ser Lys Ile Tyr
405 410 415Phe Arg Asn Pro Met Ala Glu Asn Ser Lys Phe Phe Lys Lys His Gly
420 425 430Ile Arg Asn Gly Ile Asn Pro Ala Met Tyr Gln Ser Pro Met Arg Leu
435 440 445Arg Ser Ser Thr Ile Gln Ser Ser Ser Ile Ile Leu Leu Asp Thr Leu
450 455 460Leu Leu Thr Glu Asn Glu Gly Asp Lys Thr Glu Glu Gln Val Ser Tyr465 470 475 480Val<210>436<211>387<212>PRT<213>智人(Homo sapiens)<400>436Met Asp Lys Leu Asp Ala Asn Val Ser Ser Glu Glu Gly Phe Gly Ser1 5 10 15Val Glu Lys Val Val Leu Leu Thr Phe Leu Ser Thr Val Ile Leu Met
20 25 30Ala Ile Leu Gly Asn Leu Leu Val Met Val Ala Val Cys Trp Asp Arg
35 40 45Gln Leu Arg Lys Ile Lys Thr Asn Tyr Phe Ile Val Ser Leu Ala Phe
50 55 60Ala Asp Leu Leu Val Ser Val Leu Val Met Pro Phe GIy Ala Ile Glu65 70 75 80Leu Val Gln Asp Ile Trp Ile Tyr Gly Glu Val Phe Cys Leu Val Arg
85 90 95Thr Ser Leu Asp Val Leu Leu Thr Thr Ala Ser Ile Phe His Leu Cys
100 105 110Cys Ile Ser Leu Asp Arg Tyr Tyr Ala Ile Cys Cys Gln Pro Leu Val
115 120 125Tyr Arg Asn Lys Met Thr Pro Leu Arg Ile Ala Leu Met Leu Gly Gly
130 135 140Cys Trp Val Ile Pro Thr Phe Ile Ser Phe Leu Pro Ile Met Gln Gly145 150 155 160Trp Asn Asn Ile Gly Ile Ile Asp Leu Ile Glu Lys Arg Lys Phe Asn
165 170 175Gln Asn Ser Asn Ser Thr Tyr Cys Val Phe Met Val Asn Lys Pro Tyr
180 185 190Ala Ile Thr Cys Ser Val Val Ala Phe Tyr Ile Pro Phe Leu Leu Met
195 200 205Val Leu Ala Tyr Tyr Arg Ile Tyr Val Thr Ala Lys Glu His Ala His
210 215 220Gln Ile Gln Met Leu Gln Arg Ala Gly Ala Ser Ser Glu Ser Arg Pro225 230 235 240Gln Ser Ala Asp Gln His Ser Thr His Arg Met Arg Thr Glu Thr Lys
245 250 255Ala Lys Lys Thr Leu Cys Ile Ile Met Gly Cys Phe Cys Leu Cys Trp
260 265 270Ala Pro Phe Phe Val Thr Asn Ile Val Asp Pro Phe Ile Asp Tyr Thr
275 280 285Val Pro Gly Gln Val Trp Thr Ala Phe Leu Trp Leu Gly Tyr Ile Asn
290 295 300Ser Gly Leu Asn Pro Phe Leu Tyr Ala Phe Leu Asn Lys Ser Phe Arg305 310 315 320Arg Ala Phe Leu Ile Ile Leu Cys Cys Asp Asp Glu Arg Tyr Arg Arg
325 330 335Pro Ser Ile Leu Gly Gln Thr Val Pro Cys Ser Thr Thr Thr Ile Asn
340 345 350Gly Ser Thr His Val Leu Arg Tyr Thr Val Leu His Arg Gly His His
355 360 365Gln Glu Leu Glu Lys Leu Pro Ile His Asn Asp Pro Glu Ser Leu Glu
370 375 380Ser Cys Phe385<210>437<211>1164<212>DNA<213>智人(Homo sapiens)<400>437atggacaaac ttgatgctaa tgtgagttct gaggagggtt tcgggtcagt ggagaaggtg 60gtgctgctca cgtttctctc gacggttatc ctgatggcca tcttggggaa cctgctggtg 120atggtggctg tgtgctggga caggcagctc aggaaaataa aaacaaatta tttcattgta 180tctcttgctt ttgcggatct gctggtttcg gtgctggtga tgccctttgg tgccattgag 240ctggttcaag acatctggat ttatggggag gtgttttgtc ttgttcggac atctctggac 300gtcctgctca caacggcatc gatttttcac ctgtgctgca tttctctgga taggtattac 360gccatctgct gccagccttt ggtctatagg aacaagatga cccctctgcg catcgcatta 420atgctgggag gctgctgggt catccccacg tttatttctt ttctccctat aatgcaaggc 480tggaataaca ttggcataat tgatttgata gaaaagagga agttcaacca gaactctaac 540tctacgtact gtgtcttcat ggtcaacaag ccctacgcca tcacctgctc tgtggtggcc 600ttctacatcc catttctcct catggtgctg gcctattacc gcatctatgt cacagctaag 660gagcatgccc atcagatcca gatgttacaa cgggcaggag cctcctccga gagcaggcct 720cagtcggcag accagcatag cactcatcgc atgaggacag agaccaaagc aaagaagacc 780ctgtgcatca tcatgggttg cttctgcctc tgctgggcac cattctttgt caccaatatt 840gtggatcctt tcatagacta cactgtccct gggcaggtgt ggactgcttt cctctggctc 900ggctatatca attccgggtt gaaccctttt ctctacgcct tcttgaataa gtcttttaga 960cgtgccttcc tcatcatcct ctgctgtgat gatgagcgct accgaagacc ttccattctg 1020ggccagactg tcccttgttc aaccacaacc attaatggat ccacacatgt actaaggtac 1080accgttctgc acaggggaca tcatcaggaa ctcgagaaac tgcccataca caatgaccca 1140gaatccctgg aatcatgctt ctga 1164<210>438<211>1167<212>DNA<213>智人(Homo sapiens)<400>438atggacaaac ttgatgctaa tgtgagttct gaggagggtt tcgggtcagt ggagaaggtg 60gtgctgctca cgtttctctc gacggttatc ctgatggcca tcttggggaa cctgctggtg 120atggtggctg tgtgctggga caggcagctc aggaaaataa aaacaaatta tttcattgta 180tctcttgctt ttgcggatct gctggtttcg gtgctggtga tgccctttgg tgccattgag 240ctggttcaag acatctggat ttatggggag gtgttttgtc ttgttcggac atctctggac 300gtcctgctca caacggcatc gatttttcac ctgtgctgca tttctctgga taggtattac 360gccatctgct gccagccttt ggtctatagg aacaagatga cccctctgcg catcgcatta 420atgctgggag gctgctgggt catccccacg tttatttctt ttctccctat aatgcaaggc 480tggaataaca ttggcataat tgatttgata gaaaagagga agttcaacca gaactctaac 540tctacgtact gtgtcttcat ggtcaacaag ccctacgcca tcacctgctc tgtggtggcc 600ttctacatcc catttctcct catggtgctg gcctattacc gcatctatgt cacagctaag 660gagcatgccc atcagatcca gatgttacaa cgggcaggag cctcctccga gagcaggcct 720cagtcggcag accagcatag cactcatcgc atgaggacag agaccaaagc aaagaagacc 780ctgtgcatca tcatgggttg cttctgcctc tgctgggcac cattctttgt caccaatatt 840gtggatcctt tcatagacta cactgtccct gggcaggtgt ggactgcttt cctctggctc 900ggctatatca attccgggtt gaaccctttt ctctacgcct tcttgaataa gtcttttaga 960cgtgccttcc tcatcatcct ctgctgtgat gatgagcgct accgaagacc ttccattctg 1020ggccagactg tcccttgttc aaccacaacc attaatggat ccacacatgt actaagggat 1080gcagtggagt gtggtggcca gtgggagagt cagtgtcacc cgccagcaac ttctcctttg 1140gtggctgctc agcccagtga cacttag 1167<210>439<211>388<212>PRT<213>智人(Homo sapiens)<400>439Met Asp Lys Leu Asp Ala Asn Val Ser Ser Glu Glu Gly Phe Gly Ser1 5 10 15Val Glu Lys Val Val Leu Leu Thr Phe Leu Ser Thr Val Ile Leu Met
20 25 30Ala Ile Leu Gly Asn Leu Leu Val Met Val Ala Val Cys Trp Asp Arg
35 40 45Gln Leu Arg Lys Ile Lys Thr Asn Tyr Phe Ile Val Ser Leu Ala Phe
50 55 60Ala Asp Leu Leu Val Ser Val Leu Val Met Pro Phe Gly Ala Ile Glu65 70 75 80Leu Val Gln Asp Ile Trp Ile Tyr Gly Glu Val Phe Cys Leu Val Arg
85 90 95Thr Ser Leu Asp Val Leu Leu Thr Thr Ala Ser Ile Phe His Leu Cys
100 105 110Cys Ile Ser Leu Asp Arg Tyr Tyr Ala Ile Cys Cys Gln Pro Leu Val
115 120 125Tyr Arg Asn Lys Met Thr Pro Leu Arg Ile Ala Leu Met Leu Gly Gly
130 135 140Cys Trp Val Ile Pro Thr Phe Ile Ser Phe Leu Pro Ile Met Gln Gly145 150 155 160Trp Asn Asn Ile Gly Ile Ile Asp Leu Ile Glu Lys Arg Lys Phe Asn
165 170 175Gln Asn Ser Asn Ser Thr Tyr Cys Val Phe Met Val Asn Lys Pro Tyr
180 185 190Ala Ile Thr Cys Ser Val Val Ala Phe Tyr Ile Pro Phe Leu Leu Met
195 200 205Val Leu Ala Tyr Tyr Arg Ile Tyr Val Thr Ala Lys Glu His Ala His
210 215 220Gln Ile Gln Met Leu Gln Arg Ala Gly Ala Ser Ser Glu Ser Arg Pro225 230 235 240Gln Ser Ala Asp Gln His Ser Thr His Arg Met Arg Thr Glu Thr Lys
245 250 255Ala Lys Lys Thr Leu Cys Ile Ile Met Gly Cys Phe Cys Leu Cys Trp
260 265 270Ala Pro Phe Phe Val Thr Asn Ile Val Asp Pro Phe Ile Asp Tyr Thr
275 280 285Val Pro Gly Gln Val Trp Thr Ala Phe Leu Trp Leu Gly Tyr Ile Asn
290 295 300Ser Gly Leu Asn Pro Phe Leu Tyr Ala Phe Leu Asn Lys Ser Phe Arg305 310 315 320Arg Ala Phe Leu Ile Ile Leu Cys Cys Asp Asp Glu Arg Tyr Arg Arg
325 330 335Pro Ser Ile Leu Gly Gln Thr Val Pro Cys Ser Thr Thr Thr Ile Asn
340 345 350Gly Ser Thr His Val Leu Arg Asp Ala Val Glu Cys Gly Gly Gln Trp
355 360 365Glu Ser Gln Cys His Pro Pro Ala Thr Ser Pro Leu Val Ala Ala Gln
370 375 380Pro Ser Asp Thr385<210>440<211>1152<212>DNA<213>智人(Homo sapiens)<400>440atggacaaac ttgatgctaa tgtgagttct gaggagggtt tcgggtcagt ggagaaggtg 60gtgctgctca cgtttctctc gacggttatc ctgatggcca tcttggggaa cctgctggtg 120atggtggctg tgtgctggga caggcagctc aggaaaataa aaacaaatta tttcattgta 180tctcttgctt ttgcggatct gctggtttcg gtgctggtga tgccctttgg tgccattgag 240ctggttcaag acatctggat ttatggggag gtgttttgtc ttgttcggac atctctggac 300gtcctgctca caacggcatc gatttttcac ctgtgctgca tttctctgga taggtattac 360gccatctgct gccagccttt ggtctatagg aacaagatga cccctctgcg catcgcatta 420atgctgggag gctgctgggt catccccacg tttatttctt ttctccctat aatgcaaggc 480tggaataaca ttggcataat tgatttgata gaaaagagga agttcaacca gaactctaac 540tctacgtact gtgtcttcat ggtcaacaag ccctacgcca tcacctgctc tgtggtggcc 600ttctacatcc catttctcct catggtgctg gcctattacc gcatctatgt cacagctaag 660gagcatgccc atcagatcca gatgttacaa cgggcaggag cctcctccga gagcaggcct 720cagtcggcag accagcatag cactcatcgc atgaggacag agaccaaagc aaagaagacc 780ctgtgcatca tcatgggttg cttctgcctc tgctgggcac cattctttgt caccaatatt 840gtggatcctt tcatagacta cactgtccct gggcaggtgt ggactgcttt cctctggctc 900ggctatatca attccgggtt gaaccctttt ctctacgcct tcttgaataa gtcttttaga 960cgtgccttcc tcatcatcct ctgctgtgat gatgagcgct accgaagacc ttccattctg 1020ggccagactg tcccttgttc aaccacaacc attaatggat ccacacatgt actaagttct 1080ggaactgaaa ccgacagaag aaactttgga ataaggaaga gaagattgac caaaccatcc 1140taatgccaaa aa 1152<210>441<211>380<212>PRT<213>智人(Homo sapiens)<400>441Met Asp Lys Leu Asp Ala Asn Val Ser Ser Glu Glu Gly Phe Gly Ser1 5 10 15Val Glu Lys Val Val Leu Leu Thr Phe Leu Ser Thr Val Ile Leu Met
20 25 30Ala Ile Leu Gly Asn Leu Leu Val Met Val Ala Val Cys Trp Asp Arg
35 40 45Gln Leu Arg Lys Ile Lys Thr Asn Tyr Phe Ile Val Ser Leu Ala Phe
50 55 60Ala Asp Leu Leu Val Ser Val Leu Val Met Pro Phe Gly Ala Ile Glu65 70 75 80Leu Val Gln Asp Ile Trp Ile Tyr Gly Glu Val Phe Cys Leu Val Arg
85 90 95Thr Ser Leu Asp Val Leu Leu Thr Thr Ala Ser Ile Phe His Leu Cys
100 105 110Cys Ile Ser Leu Asp Arg Tyr Tyr Ala Ile Cys Cys Gln Pro Leu Val
115 120 125Tyr Arg Asn Lys Met Thr Pro Leu Arg Ile Ala Leu Met Leu Gly Gly
130 135 140Cys Trp Val Ile Pro Thr Phe Ile Ser Phe Leu Pro Ile Met Gln Gly145 150 155 160Trp Asn Asn Ile Gly Ile Ile Asp Leu Ile Glu Lys Arg Lys Phe Asn
165 170 175Gln Asn Ser Asn Ser Thr Tyr Cys Val Phe Met Val Asn Lys Pro Tyr
180 185 190Ala Ile Thr Cys Ser Val Val Ala Phe Tyr Ile Pro Phe Leu Leu Met
195 200 205Val Leu Ala Tyr Tyr Arg Ile Tyr Val Thr Ala Lys Glu His Ala His
210 215 220Gln Ile Gln Met Leu Gln Arg Ala Gly Ala Ser Ser Glu Ser Arg Pro225 230 235 240Gln Ser Ala Asp Gln His Ser Thr His Arg Met Arg Thr Glu Thr Lys
245 250 255Ala Lys Lys Thr Leu Cys Ile Ile Met Gly Cys Phe Cys Leu Cys Trp
260 265 270Ala Pro Phe Phe Val Thr Asn Ile Val Asp Pro Phe Ile Asp Tyr Thr
275 280 285Val Pro Gly Gln Val Trp Thr Ala Phe Leu Trp Leu Gly Tyr Ile Asn
290 295 300Ser Gly Leu Asn Pro Phe Leu Tyr Ala Phe Leu Asn Lys Ser Phe Arg305 310 315 320Arg Ala Phe Leu Ile Ile Leu Cys Cys Asp Asp Glu Arg Tyr Arg Arg
325 330 335Pro Ser Ile Leu Gly Gln Thr Val Pro Cys Ser Thr Thr Thr Ile Asn
340 345 350Gly Ser Thr His Val Leu Ser Ser Gly Thr Glu Thr Asp Arg Arg Asn
355 360 365Phe Gly Ile Arg Lys Arg Arg Leu Thr Lys Pro Ser
370 375 380<210>442<211>1083<212>DNA<213>智人(Homo sapiens)<400>442atggacaaac ttgatgctaa tgtgagttct gaggagggtt tcgggtcagt ggagaaggtg 60gtgctgctca cgtttctctc gacggttatc ctgatggcca tcttggggaa cctgctggtg 120atggtggctg tgtgctggga caggcagctc aggaaaataa aaacaaatta tttcattgta 180tctcttgctt ttgcggatct gctggtttcg gtgctggtga tgccctttgg tgccattgag 240ctggttcaag acatctggat ttatggggag gtgttttgtc ttgttcggac atctctggac 300gtcctgctca caacggcatc gatttttcac ctgtgctgca tttctctgga taggtattac 360gccatctgct gccagccttt ggtctatagg aacaagatga cccctctgcg catcgcatta 420atgctgggag gctgctgggt catccccacg tttatttctt ttctccctat aatgcaaggc 480tggaataaca ttggcataat tgatttgata gaaaagagga agttcaacca gaactctaac 540tctacgtact gtgtcttcat ggtcaacaag ccctacgcca tcacctgctc tgtggtggcc 600ttctacatcc catttctcct catggtgctg gcctattacc gcatctatgt cacagctaag 660gagcatgccc atcagatcca gatgttacaa cgggcaggag cctcctccga gagcaggcct 720cagtcggcag accagcatag cactcatcgc atgaggacag agaccaaagc aaagaagacc 780ctgtgcatca tcatgggttg cttctgcctc tgctgggcac cattctttgt caccaatatt 840gtggatcctt tcatagacta cactgtccct gggcaggtgt ggactgcttt cctctggctc 900ggctatatca attccgggtt gaaccctttt ctctacgcct tcttgaataa gtcttttaga 960cgtgccttcc tcatcatcct ctgctgtgat gatgagcgct accgaagacc ttccattctg 1020ggccagactg tcccttgttc aaccacaacc attaatggat ccacacatgt actaagattt 1080tga 1083<210>443<211>360<212>PRT<213>智人(Homo sapiens)<400>443Met Asp Lys Leu Asp Ala Asn Val Ser Ser Glu Glu Gly Phe Gly Ser1 5 10 15Val Glu Lys Val Val Leu Leu Thr Phe Leu Ser Thr Val Ile Leu Met
20 25 30Ala Ile Leu Gly Asn Leu Leu Val Met Val Ala Val Cys Trp Asp Arg
35 40 45Gln Leu Arg Lys Ile Lys Thr Asn Tyr Phe Ile Val Ser Leu Ala Phe
50 55 60Ala Asp Leu Leu Val Ser Val Leu Val Met Pro Phe Gly Ala Ile Glu65 70 75 80Leu Val Gln Asp Ile Trp Ile Tyr Gly Glu Val Phe Cys Leu Val Arg
85 90 95Thr Ser Leu Asp Val Leu Leu Thr Thr Ala Ser Ile Phe His Leu Cys
100 105 110Cys Ile Ser Leu Asp Arg Tyr Tyr Ala Ile Cys Cys Gln Pro Leu Val
115 120 125Tyr Arg Asn Lys Met Thr Pro Leu Arg Ile Ala Leu Met Leu Gly Gly
130 135 140Cys Trp Val Ile Pro Thr Phe Ile Ser Phe Leu Pro Ile Met Gln Gly145 150 155 160Trp Asn Asn Ile Gly Ile Ile Asp Leu Ile Glu Lys Arg Lys Phe Asn
165 170 175Gln Asn Ser Asn Ser Thr Tyr Cys Val Phe Met Val Asn Lys Pro Tyr
180 185 190Ala Ile Thr Cys Ser Val Val Ala Phe Tyr Ile Pro Phe Leu Leu Met
195 200 205Val Leu Ala Tyr Tyr Arg Ile Tyr Val Thr Ala Lys Glu His Ala His
210 215 220Gln Ile Gln Met Leu Gln Arg Ala Gly Ala Ser Ser Glu Ser Arg Pro225 230 235 240Gln Ser Ala Asp Gln His Ser Thr His Arg Met Arg Thr Glu Thr Lys
245 250 255Ala Lys Lys Thr Leu Cys Ile Ile Met Gly Cys Phe Cys Leu Cys Trp
260 265 270Ala Pro Phe Phe Val Thr Asn Ile Val Asp Pro Phe Ile Asp Tyr Thr
275 280 285Val Pro Gly Gln Val Trp Thr Ala Phe Leu Trp Leu Gly Tyr Ile Asn
290 295 300Ser Gly Leu Asn Pro Phe Leu Tyr Ala Phe Leu Asn Lys Ser Phe Arg305 310 315 320Arg Ala Phe Leu Ile Ile Leu Cys Cys Asp Asp Glu Arg Tyr Arg Arg
325 330 335Pro Ser Ile Leu Gly Gln Thr Val Pro Cys Ser Thr Thr Thr Ile Asn
340 345 350Gly Ser Thr His Val Leu Arg Phe
355 360<210>444<211>1137<212>DNA<213>智人(Homo sapiens)<400>444atggacaaac ttgatgctaa tgtgagttct gaggagggtt tcgggtcagt ggagaaggtg 60gtgctgctca cgtttctctc gacggttatc ctgatggcca tcttggggaa cctgctggtg 120atggtggctg tgtgctggga caggcagctc aggaaaataa aaacaaatta tttcattgta 180tctcttgctt ttgcggatct gctggtttcg gtgctggtga tgccctttgg tgccattgag 240ctggttcaag acatctggat ttatggggag gtgttttgtc ttgttcggac atctctggac 300gtcctgctca caacggcatc gatttttcac ctgtgctgca tttctctgga taggtattac 360gccatctgct gccagccttt ggtctatagg aacaagatga cccctctgcg catcgcatta 420atgctgggag gctgctgggt catccccacg tttatttctt ttctccctat aatgcaaggc 480tggaataaca ttggcataat tgatttgata gaaaagagga agttcaacca gaactctaac 540tctacgtact gtgtcttcat ggtcaacaag ccctacgcca tcacctgctc tgtggtggcc 600ttctacatcc catttctcct catggtgctg gcctattacc gcatctatgt cacagctaag 660gagcatgccc atcagatcca gatgttacaa cgggcaggag cctcctccga gagcaggcct 720cagtcggcag accagcatag cactcatcgc atgaggacag agaccaaagc aaagaagacc 780ctgtgcatca tcatgggttg cttctgcctc tgctgggcac cattctttgt caccaatatt 840gtggatcctt tcatagacta cactgtccct gggcaggtgt ggactgcttt cctctggctc 900ggctatatca attccgggtt gaaccctttt ctctacgcct tcttgaataa gtcttttaga 960cgtgccttcc tcatcatcct ctgctgtgat gatgagcgct accgaagacc ttccattctg 1020ggccagactg tcccttgttc aaccacaacc attaatggat ccacacatgt actaagtggc 1080tgttcccctg tctccagctt cctcctgctc ttctgcaata gaccagttcc tgtctaa 1137<210>445<211>378<212>PRT<213>智人(Homo sapiens)<400>445Met Asp Lys Leu Asp Ala Asn Val Ser Ser Glu Glu Gly Phe Gly Ser1 5 10 15Val Glu Lys Val Val Leu Leu Thr Phe Leu Ser Thr Val Ile Leu Met
20 25 30Ala Ile Leu Gly Asn Leu Leu Val Met Val Ala Val Cys Trp Asp Arg
35 40 45Gln Leu Arg Lys Ile Lys Thr Asn Tyr Phe Ile Val Ser Leu Ala Phe
50 55 60Ala Asp Leu Leu Val Ser Val Leu Val Met Pro Phe Gly Ala Ile Glu65 70 75 80Leu Val Gln Asp Ile Trp Ile Tyr Gly Glu Val Phe Cys Leu Val Arg
85 90 95Thr Ser Leu Asp Val Leu Leu Thr Thr Ala Ser Ile Phe His Leu Cys
100 105 110Cys Ile Ser Leu Asp Arg Tyr Tyr Ala Ile Cys Cys Gln Pro Leu Val
115 120 125Tyr Arg Asn Lys Met Thr Pro Leu Arg Ile Ala Leu Met Leu Gly Gly
130 135 140Cys Trp Val Ile Pro Thr Phe Ile Ser Phe Leu Pro Ile Met Gln Gly145 150 155 160Trp Asn Asn Ile Gly Ile Ile Asp Leu Ile Glu Lys Arg Lys Phe Asn
165 170 175Gln Asn Ser Asn Ser Thr Tyr Cys Val Phe Met Val Asn Lys Pro Tyr
180 185 190Ala Ile Thr Cys Ser Val Val Ala Phe Tyr Ile Pro Phe Leu Leu Met
195 200 205Val Leu Ala Tyr Tyr Arg Ile Tyr Val Thr Ala Lys Glu His Ala His
210 215 220Gln Ile Gln Met Leu Gln Arg Ala Gly Ala Ser Ser Glu Ser Arg Pro225 230 235 240Gln Ser Ala Asp Gln His Ser Thr His Arg Met Arg Thr Glu Thr Lys
245 250 255Ala Lys Lys Thr Leu Cys Ile Ile Met Gly Cys Phe Cys Leu Cys Trp
260 265 270Ala Pro Phe Phe Val Thr Asn Ile Val Asp Pro Phe Ile Asp Tyr Thr
275 280 285Val Pro Gly Gln Val Trp Thr Ala Phe Leu Trp Leu Gly Tyr Ile Asn
290 295 300Ser Gly Leu Asn Pro Phe Leu Tyr Ala Phe Leu Asn Lys Ser Phe Arg305 310 315 320Arg Ala Phe Leu Ile Ile Leu Cys Cys Asp Asp Glu Arg Tyr Arg Arg
325 330 335Pro Ser Ile Leu Gly Gln Thr Val Pro Cys Ser Thr Thr Thr Ile Asn
340 345 350Gly Ser Thr His Val Leu Ser Gly Cys Ser Pro Val Ser Ser Phe Leu
355 360 365Leu Leu Phe Cys Asn Arg Pro Val Pro Val
370 375<210>446<211>1074<212>DNA<213>智人(Homo sapiens)<400>446atggatttac cagtgaacct aacctccttt tccctctcca ccccctcccc tttggagacc 60aaccacagcc tcggcaaaga cgacctgcgc cccagctcgc ccctgctctc ggtcttcgga 120gtgcttattc tcaccttgct gggctttctg gtggcggcga cgttcgcctg gaacctgctg 180gtgctggcga ccatcctccg tgtacgcacc ttccaccgcg tgccccacaa cctggtggca 240tccatggccg tctcggatgt cctggtggcc gcgctggtca tgccgctgag cctggtgcat 300gagctgtccg ggcgccgctg gcagctaggt cggaggctgt gccagctttg gatcgcgtgc 360gacgtgcttt gctgcacggc cagcatctgg aacgtgacgg ccatagccct ggaccgctac 420tggtccatca cgcgccacat ggaatacacg ctccgcaccc gcaagtgcgt ctccaacgtc 480atgatcgcgc tcacctgggc actctccgct gtcatctctc tggccccgct gctttttggc 540tggggagaga cgtactctga gggcagcgag gagtgccagg taagccgcga gccttcctac 600gccgtgttct ccaccgtagg cgccttctac ctgccgctct gtgtggtgct cttcgtgtac 660tggaagatct acaaggctgc caagttccgc gtgggctcca ggaagaccaa tagcgtctca 720cccatatccg aagctgtgga ggtgaaggac tctgccaaac agccccagat ggtgttcacg 780gtccgccacg ccaccgtcac cttccagcca gaaggggaca cgtggcggga gcagaaggag 840cagcgggcca agctcatggt gggcatcctc attggcgtgt tcgtgctctg ctggatcccc 900ttctttctca ccgagctcat cagtcccctc tgctcctgtg acatccccgc catctggaaa 960agcatcttcc tgtggcttgg ctactccaac tccttcttta accccctgat ctatacggct 1020ttcaacaaga actacaacag cgccttcaag aacttctttt ctaggcaaca ctga 1074<210>447<211>357<212>PRT<213>智人(Homo sapiens)<400>447Met Asp Leu Pro Val Asn Leu Thr Ser Phe Ser Leu Ser Thr Pro Ser1 5 10 15Pro Leu Glu Thr Asn His Ser Leu Gly Lys Asp Asp Leu Arg Pro Ser
20 25 30Ser Pro Leu Leu Ser Val Phe Gly Val Leu Ile Leu Thr Leu Leu Gly
35 40 45Phe Leu Val Ala Ala Thr Phe Ala Trp Asn Leu Leu Val Leu Ala Thr
50 55 60Ile Leu Arg Val Arg Thr Phe His Arg Val Pro His Asn Leu Val Ala65 70 75 80Ser Met Ala Val Ser Asp Val Leu Val Ala Ala Leu Val Met Pro Leu
85 90 95Ser Leu Val His Glu Leu Ser Gly Arg Arg Trp Gln Leu Gly Arg Arg
100 105 110Leu Cys Gln Leu Trp Ile Ala Cys Asp Val Leu Cys Cys Thr Ala Ser
115 120 125Ile Trp Asn Val Thr Ala Ile Ala Leu Asp Arg Tyr Trp Ser Ile Thr
130 135 140Arg His Met Glu Tyr Thr Leu Arg Thr Arg Lys Cys Val Ser Asn Val145 150 155 160Met Ile Ala Leu Thr Trp Ala Leu Ser Ala Val Ile Ser Leu Ala Pro
165 170 175Leu Leu Phe Gly Trp Gly Glu Thr Tyr Ser Glu Gly Ser Glu Glu Cys
180 185 190Gln Val Ser Arg Glu Pro Ser Tyr Ala Val Phe Ser Thr Val Gly Ala
195 200 205Phe Tyr Leu Pro Leu Cys Val Val Leu Phe Val Tyr Trp Lys Ile Tyr
210 215 220Lys Ala Ala Lys Phe Arg Val Gly Ser Arg Lys Thr Asn Ser Val Ser225 230 235 240Pro Ile Ser Glu Ala Val Glu Val Lys Asp Ser Ala Lys Gln Pro Gln
245 250 255Met Val Phe Thr Val Arg His Ala Thr Val Thr Phe Gln Pro Glu Gly
260 265 270Asp Thr Trp Arg Glu Gln Lys Glu Gln Arg Ala Lys Leu Met Val Gly
275 280 285Ile Leu Ile Gly Val Phe Val Leu Cys Trp Ile Pro Phe Phe Leu Thr
290 295 300Glu Leu Ile Ser Pro Leu Cys Ser Cys Asp Ile Pro Ala Ile Trp Lys305 310 315 320Ser Ile Phe Leu Trp Leu Gly Tyr Ser Asn Ser Phe Phe Asn Pro Leu
325 330 335Ile Tyr Thr Ala Phe Asn Lys Asn Tyr Asn Ser Ala Phe Lys Asn Phe
340 345 350Phe Ser Arg Gln His
355<210>448<211>1323<212>DNA<213>智人(Homo sapiens)<400>448atggtcccag agccgggccc aaccgccaat agcaccccgg cctggggggc agggccgccg 60tcggccccgg ggggcagcgg ctgggtggcg gccgcgctgt gcgtggtcat cgcgctgacg 120gcggcggcca actcgctgct gatcgcgctc atctgcactc agcccgcgct gcgcaacacg 180tccaacttct tcctggtgtc gctcttcacg tctgacctga tggtggggct ggtggtgatg 240ccgccggcca tgctgaacgc gctgtacggg cgctgggtgc tggcgcgcgg cctctgcctg 300ctctggaccg ccttcgacgt gatgtgctgc agcgcctcca tcctcaacct ctgcctcatc 360agcctggacc gctacctgct catcctctcg ccgctgcgct acaagctgcg catgacgccc 420ctgcgtgccc tggccctagt cctgggcgcc tggagcctcg ccgctctcgc ctccttcctg 480cccctgctgc tgggctggca cgagctgggc cacgcacggc cacccgtccc tggccagtgc 540cgcctgctgg ccagcctgcc ttttgtcctt gtggcgtcgg gcctcacctt cttcctgccc 600tcgggtgcca tatgcttcac ctactgcagg atcctgctag ctgcccgcaa gcaggccgtg 660caggtggcct ccctcaccac cggcatggcc agtcaggcct cggagacgct gcaggtgccc 720aggaccccac gcccaggggt ggagtctgct gacagcaggc gtctagccac gaagcacagc 780aggaaggccc tgaaggccaa gctgacgctg ggcatcctgc tgggcatgtt ctttgtgacc 840tggttgccct tctttgtggc caacatagtc caggccgtgt gcgactgcat ctccccaggc 900ctcttcgatg tcctcacatg gctgggttac tgtaacagca ccatgaaccc catcatctac 960ccactcttca tgcgggactt caagcgggcg ctgggcaggt tcctgccatg tccacgctgt 1020ccccgggagc gccaggccag cctggcctcg ccatcactgc gcacctctca cagcggcccc 1080cggcccggcc ttagcctaca gcaggtgctg ccgctgcccc tgccgccgga ctcagattcg 1140gactcagacg caggctcagg cggctcctcg ggcctgcggc tcacggccca gctgctgctt 1200cctggcgagg ccacccagga ccccccgctg cccaccaggg ccgctgccgc cgtcaatttc 1260ttcaacatcg accccgcgga gcccgagctg cggccgcatc cacttggcat ccccacgaac 1320tga 1323<210>449<211>440<212>PRT<213>智人(Homo sapiens)<400>449Met Val Pro Glu Pro Gly Pro Thr Ala Asn Ser Thr Pro Ala Trp Gly1 5 10 15Ala Gly Pro Pro Ser Ala Pro Gly Gly Ser Gly Trp Val Ala Ala Ala
20 25 30Leu Cys Val Val Ile Ala Leu Thr Ala Ala Ala Asn Ser Leu Leu Ile
35 40 45Ala Leu Ile Cys Thr Gln Pro Ala Leu Arg Asn Thr Ser Asn Phe Phe
50 55 60Leu Val Ser Leu Phe Thr Ser Asp Leu Met Val Gly Leu Val Val Met65 70 75 80Pro Pro Ala Met Leu Asn Ala Leu Tyr Gly Arg Trp Val Leu Ala Arg
85 90 95Gly Leu Cys Leu Leu Trp Thr Ala Phe Asp Val Met Cys Cys Ser Ala
100 105 110Ser Ile Leu Asn Leu Cys Leu Ile Ser Leu Asp Arg Tyr Leu Leu Ile
115 120 125Leu Ser Pro Leu Arg Tyr Lys Leu Arg Met Thr Pro Leu Arg Ala Leu
130 135 140Ala Leu Val Leu Gly Ala Trp Ser Leu Ala Ala Leu Ala Ser Phe Leu145 150 155 160Pro Leu Leu Leu Gly Trp His Glu Leu Gly His Ala Arg Pro Pro Val
165 170 175Pro Gly Gln Cys Arg Leu Leu Ala Ser Leu Pro Phe Val Leu Val Ala
180 185 190Ser Gly Leu Thr Phe Phe Leu Pro Ser Gly Ala Ile Cys Phe Thr Tyr
195 200 205Cys Arg Ile Leu Leu Ala Ala Arg Lys Gln Ala Val Gln Val Ala Ser
210 215 220Leu Thr Thr Gly Met Ala Ser Gln Ala Ser Glu Thr Leu Gln Val Pro225 230 235 240Arg Thr Pro Arg Pro Gly Val Glu Ser Ala Asp Ser Arg Arg Leu Ala
245 250 255Thr Lys His Ser Arg Lys Ala Leu Lys Ala Lys Leu Thr Leu Gly Ile
260 265 270Leu Leu Gly Met Phe Phe Val Thr Trp Leu Pro Phe Phe Val Ala Asn
275 280 285Ile Val Gln Ala Val Cys Asp Cys Ile Ser Pro Gly Leu Phe Asp Val
290 295 300Leu Thr Trp Leu Gly Tyr Cys Asn Ser Thr Met Asn Pro Ile Ile Tyr305 310 315 320Pro Leu Phe Met Arg Asp Phe Lys Arg Ala Leu Gly Arg Phe Leu Pro
325 330 335Cys Pro Arg Cys Pro Arg Glu Arg Gln Ala Ser Leu Ala Ser Pro Ser
340 345 350Leu Arg Thr Ser His Ser Gly Pro Arg Pro Gly Leu Ser Leu Gln Gln
355 360 365Val Leu Pro Leu Pro Leu Pro Pro Asp Ser Asp Ser Asp Ser Asp Ala
370 375 380Gly Ser Gly Gly Ser Ser Gly Leu Arg Leu Thr Ala Gln Leu Leu Leu385 390 395 400Pro Gly Glu Ala Thr Gln Asp Pro Pro Leu Pro Thr Arg Ala Ala Ala
405 410 415Ala Val Asn Phe Phe Asn Ile Asp Pro Ala Glu Pro Glu Leu Arg Pro
420 425 430His Pro Leu Gly Ile Pro Thr Asn
435 440<210>450<211>1379<212>DNA<213>智人(Homo sapiens)<400>450atgatggacg ttaacagcag cggccgcccg gacctctacg ggcacctccg ctctttcctt 60ctgccagaag tggggcgcgg gctgcccgac ttgagccccg acggtggcgc cgacccggtc 120gcgggctcct gggcgccgca cctgctgagc gaggtgacag ccagcccggc gcccacctgg 180gacgcgcccc cggacaatgc ctccggctgt ggggaacaga tcaactacgg cagagtcgag 240aaagttgtga tcggctccat cctgacgctc atcacgctgc tgacgatcgc gggcaactgc 300ctggtggtga tctccgtgtg cttcgtcaag aagctccgcc agccctccaa ctacctgatc 360gtgtccctgg cgctggccga cctctcggtg gctgtggcgg tcatgccctt cgtcagcgtc 420accgacctca tcgggggcaa gtggatcttt ggacactttt tctgtaatgt cttcatcgcc 480atggacgtca tgtgctgcac ggcctcgatc atgaccctgt gcgtgatcag cattgacagg 540taccttggga tcacaaggcc cctcacatac cctgtgaggc agaatgggaa atgcatggcg 600aagatgattc tctccgtctg gcttctctcc gcctccatca ccttacctcc actctttgga 660tgggctcaga atgtaaatga tgataaggtg tgcttgatca gccaggactt tggctatacg 720atttactcta ccgcagtggc attttatatc cccatgtccg tcatgctttt catgtactac 780cagatttaca aggctgccag gaagagtgct gccaaacaca agtttcctgg cttccctcga 840gtggagccag acagcgtcat cgccctgaat ggcatagtga agctccagaa ggaggtggaa 900gagtgtgcaa acctttcgag actcctcaag catgaaagga aaaacatctc catctttaag 960cgagaacaga aagcaaagac caccctgggg atcatcgtcg gggcctttac cgtgtgctgg 1020ctgccatttt tcctcctctc gacagccaga cccttcatct gtggcacttc ctgcagctgc 1080atcccactgt gggtggagag gacatttctg tggctaggct atgcaaactc tctcattaac 1140ccttttatat atgccttctt caaccgggac ctgaggacca cctatcgcag cctgctccag 1200tgccagtacc ggaatatcaa ccggaagctc tcagctgcag gcatgcatga agccctgaag 1260cttgctgaga ggccagagag acctgagttt gtgctacaaa atgctgacta ctgtagaaaa 1320aaaggtcatg attcatgatt gaaagcagaa caatggagag gaattcgata tcaagctta 1379<210>451<211>445<212>PRT<213>智人(Homo sapiens)<400>451Met Met Asp Val Asn Ser Ser Gly Arg Pro Asp Leu Tyr Gly His Leu1 5 10 15Arg Ser Phe Leu Leu Pro Glu Val Gly Arg Gly Leu Pro Asp Leu Ser
20 25 30Pro Asp Gly Gly Ala Asp Pro Val Ala Gly Ser Trp Ala Pro His Leu
35 40 45Leu Ser Glu Val Thr Ala Ser Pro Ala Pro Thr Trp Asp Ala Pro Pro
50 55 60Asp Asn Ala Ser Gly Cys Gly Glu Gln Ile Asn Tyr Gly Arg Val Glu65 70 75 80Lys Val Val Ile Gly Ser Ile Leu Thr Leu Ile Thr Leu Leu Thr Ile
85 90 95Ala Gly Asn Cys Leu Val Val Ile Ser Val Cys Phe Val Lys Lys Leu
100 105 110Arg Gln Pro Ser Asn Tyr Leu Ile Val Ser Leu Ala Leu Ala Asp Leu
115 120 125Ser Val Ala Val Ala Val Met Pro Phe Val Ser Val Thr Asp Leu Ile
130 135 140Gly Gly Lys Trp Ile Phe Gly His Phe Phe Cys Asn Val Phe Ile Ala145 150 155 160Met Asp Val Met Cys Cys Thr Ala Ser Ile Met Thr Leu Cys Val Ile
165 170 175Ser Ile Asp Arg Tyr Leu Gly Ile Thr Arg Pro Leu Thr Tyr Pro Val
180 185 190Arg Gln Asn Gly Lys Cys Met Ala Lys Met Ile Leu Ser Val Trp Leu
195 200 205Leu Ser Ala Ser Ile Thr Leu Pro Pro Leu Phe Gly Trp Ala Gln Asn
210 215 220Val Asn Asp Asp Lys Val Cys Leu Ile Ser Gln Asp Phe Gly Tyr Thr225 230 235 240Ile Tyr Ser Thr Ala Val Ala Phe Tyr Ile Pro Met Ser Val Met Leu
245 250 255Phe Met Tyr Tyr Gln Ile Tyr Lys Ala Ala Arg Lys Ser Ala Ala Lys
260 265 270His Lys Phe Pro Gly Phe Pro Arg Val Glu Pro Asp Ser Val Ile Ala
275 280 285Leu Asn Gly Ile Val Lys Leu Gln Lys Glu Val Glu Glu Cys Ala Asn
290 295 300Leu Ser Arg Leu Leu Lys His Glu Arg Lys Asn Ile Ser Ile Phe Lys305 310 315 320Arg Glu Gln Lys Ala Lys Thr Thr Leu Gly Ile Ile Val Gly Ala Phe
325 330 335Thr Val Cys Trp Leu Pro Phe Phe Leu Leu Ser Thr Ala Arg Pro Phe
340 345 350Ile Cys Gly Thr Ser Cys Ser Cys Ile Pro Leu Trp Val Glu Arg Thr
355 360 365Phe Leu Trp Leu Gly Tyr Ala Asn Ser Leu Ile Asn Pro Phe Ile Tyr
370 375 380Ala Phe Phe Asn Arg Asp Leu Arg Thr Thr Tyr Arg Ser Leu Leu Gln385 390 395 400Cys Gln Tyr Arg Asn Ile Asn Arg Lys Leu Ser Ala Ala Gly Met His
405 410 415Glu Ala Leu Lys Leu Ala Glu Arg Pro Glu Arg Pro Glu Phe Val Leu
420 425 430Gln Asn Ala Asp Tyr Cys Arg Lys Lys Gly His Asp Ser
435 440 445<210>452<211>1257<212>DNA<213>智人(Homo sapiens)<400>452atgcgtctct ccgccggtcc cgacgcgggg ccctcgggca actccagccc atggtggcct 60ctggccaccg gcgctggcaa cacaagccgg gaggccgaag ccctcgggga gggcaacggc 120ccaccgaggg acgtgcgcaa cgaggagctg gccaaactgg agatcgccgt gctggcggtg 180actttcgcgg tggccgtgct gggcaacagc agcgtactgc tggctctgca ccggacgccg 240cgcaagacgt cccgcatgca cctcttcatc cgacacctca gcctggccga cctggccgtg 300gcattcttcc aggtgctgcc gcaaatgtgc tgggacatca cctaccgctt ccgcggcccc 360gactggctgt gccgcgtggt gaagcacctg caggtgttcg gcatgtttgc gtcggcctac 420atgctggtag tcatgacagc cgaccgctac atcgcggtgt gccacccgct caagactctg 480caacagcccg cgcgccgctc gcgcctcatg atcgcggccg cctgggtgct gagcttcgtg 540ctgagcacgc cgcagtactt cgtcttctcc atgatcgagg tgaacaatgt caccaaggcc 600cgcgactgct gggccacctt catccagccc tggggttctc gtgcctacgt gacctggatg 660acgggcggca tctttgtggc gcccgtggtc atcttgggta cctgctacgg cttcatctgc 720tacaacatct ggtgcaacgt ccgcgggaag acggcgtcgc gccagagcaa gggtgcagag 780caagcgggtg tggccttcca aaaggggttc ctgctcgcac cctgtgtcag cagcgtgaag 840tccatttccc gggccaagat ccgcacgaag aagatgactt ttgtgatcgt gacggcttac 900atcgtctgct gggcgccttt cttcatcatc cagatgtggt ctgtctggga tcccatgtcc 960gtctggaccg aatcggaaaa ccctaccatc accatcactg cattactggg ttccttgaat 1020agctgctgta atccctggat atacatgttt tttagtggcc atctccttca agactgtgtt 1080caaagcttcc catgctgcca aaacatgaag gaaaaattca acaaagaaga tactgacagt 1140atgagcagaa gacagacttt ttattctaac aatcgaagcc caacaaacag tacgggtatg 1200tggaaggact cgcctaaatc ttccaagtcc atcaaattca ttcctgtttc aacttga 1257<210>453<211>418<212>PRT<213>智人(Homo sapiens)<400>453Met Arg Leu Ser Ala Gly Pro Asp Ala Gly Pro Ser Gly Asn Ser Ser1 5 10 15Pro Trp Trp Pro Leu Ala Thr Gly Ala Gly Asn Thr Ser Arg Glu Ala
20 25 30Glu Ala Leu Gly Glu Gly Asn Gly Pro Pro Arg Asp Val Arg Asn Glu
35 40 45Glu Leu Ala Lys Leu Glu Ile Ala Val Leu Ala Val Thr Phe Ala Val
50 55 60Ala Val Leu Gly Asn Ser Ser Val Leu Leu Ala Leu His Arg Thr Pro65 70 75 80Arg Lys Thr Ser Arg Met His Leu Phe Ile Arg His Leu Ser Leu Ala
85 90 95Asp Leu Ala Val Ala Phe Phe Gln Val Leu Pro Gln Met Cys Trp Asp
100 105 110Ile Thr Tyr Arg Phe Arg Gly Pro Asp Trp Leu Cys Arg Val Val Lys
115 120 125His Leu Gln Val Phe Gly Met Phe Ala Ser Ala Tyr Met Leu Val Val
130 135 140Met Thr Ala Asp Arg Tyr Ile Ala Val Cys His Pro Leu Lys Thr Leu145 150 155 160Gln Gln Pro Ala Arg Arg Ser Arg Leu Met Ile Ala Ala Ala Trp Val
165 170 175Leu Ser Phe Val Leu Ser Thr Pro Gln Tyr Phe Val Phe Ser Met Ile
180 185 190Glu Val Asn Asn Val Thr Lys Ala Arg Asp Cys Trp Ala Thr Phe Ile
195 200 205Gln Pro Trp Gly Ser Arg Ala Tyr Val Thr Trp Met Thr Gly Gly Ile
210 215 220Phe Val Ala Pro Val Val Ile Leu Gly Thr Cys Tyr Gly Phe Ile Cys225 230 235 240Tyr Asn Ile Trp Cys Asn Val Arg Gly Lys Thr Ala Ser Arg Gln Ser
245 250 255Lys Gly Ala Glu Gln Ala Gly Val Ala Phe Gln Lys Gly Phe Leu Leu
260 265 270Ala Pro Cys Val Ser Ser Val Lys Ser Ile Ser Arg Ala Lys Ile Arg
275 280 285Thr Lys Lys Met Thr Phe Val Ile Val Thr Ala Tyr Ile Val Cys Trp
290 295 300Ala Pro Phe Phe Ile Ile Gln Met Trp Ser Val Trp Asp Pro Met Ser305 310 315 320Val Trp Thr Glu Ser Glu Asn Pro Thr Ile Thr Ile Thr Ala Leu Leu
325 330 335Gly Ser Leu Asn Ser Cys Cys Asn Pro Trp Ile Tyr Met Phe Phe Ser
340 345 350Gly His Leu Leu Gln Asp Cys Val Gln Ser Phe Pro Cys Cys Gln Asn
355 360 365Met Lys Glu Lys Phe Asn Lys Glu Asp Thr Asp Ser Met Ser Arg Arg
370 375 380Gln Thr Phe Tyr Ser Asn Asn Arg Ser Pro Thr Asn Ser Thr Gly Met385 390 395 400Trp Lys Asp Ser Pro Lys Ser Ser Lys Ser Ile Lys Phe Ile Pro Val
405 410 415Ser Thr<210>454<211>1275<212>DNA<213>智人(Homo sapiens)<400>454atggattctg ggcctctgtg ggatgccaac cccacccctc ggggcaccct ctctgccccc 60aatgccacaa caccctggct gggccgggat gaggagctgg ccaaggtgga gatcggagtc 120ctggccactg tcctggtgct ggcgaccggg ggcaacctgg ctgtgctgct gaccctgggc 180cagctgggcc gcaagcgctc ccgcatgcac ctgttcgtgc tgcacttagc cctgacagac 240ctggccgtgg cgctcttcca ggtgctgcca cagctgctgt gggacatcac ctaccgcttc 300cagggccccg acctcctgtg cagggccgtc aagtacctgc aggtgctcag catgtttgcc 360tccacctaca tgctgctggc catgacgctg gaccgctacc tggctgtctg tcaccccctg 420cgcagcctcc agcagccagg ccagtccacc tacctgctca tcgctgctcc ctggctgctg 480gccgccatct tcagcctccc tcaagtcttc attttttccc tgcgggaggt gatccagggc 540tcaggggtgc tggactgctg ggcagacttc ggcttccctt gggggccacg ggcctacctc 600acctggacca ccctggctat cttcgttctg ccggtgacca tgctcacggc ctgctacagc 660ctcatctgcc atgagatctg taaaaaccta aaagtcaaga cacaggcctg gcgggtggga 720ggagggggct ggaggacttg ggacaggccc tcaccttcca ccttagctgc caccactcgg 780gggctgccat ctcgggtcag cagcatcaac accatctcac gggccaagat ccgaacaaag 840aagatgacct ttgtcatcgt gctggcctac atcgcttgct gggctccctt cttcagtgtc 900cagatgtggt ccgtgtggga caagaatgcc cctgatgaag attccaccaa tgtggctttc 960accatctcta tgcttttggg caacctcaac agctgctgca acccctggat ctacatgggc 1020ttcaacagcc acctgttacc gcggcccctg cgtcaccttg cctgctgtgg gggtccccag 1080cccaggatgc gccggcggct ctccgacggc agcctctcga gccgccacac cacgctgctg 1140acccgctcca gctgcccggc caccctcagc ctcagcctca gcctaaccct cagtgggagg 1200cccaggcctg aagagtcacc aagggacttg gagctggcag atggggaagg caccgctgag 1260accatcatct tttag 1275<210>455<211>424<212>PRT<213>智人(Homo sapiens)<400>455Met Asp Ser Gly Pro Leu Trp Asp Ala Asn Pro Thr Pro Arg Gly Thr1 5 10 15Leu Ser Ala Pro Asn Ala Thr Thr Pro Trp Leu Gly Arg Asp Glu Glu
20 25 30Leu Ala Lys Val Glu Ile Gly Val Leu Ala Thr Val Leu Val Leu Ala
35 40 45Thr Gly Gly Asn Leu Ala Val Leu Leu Thr Leu Gly Gln Leu Gly Arg
50 55 60Lys Arg Ser Arg Met His Leu Phe Val Leu His Leu Ala Leu Thr Asp65 70 75 80Leu Ala Val Ala Leu Phe Gln Val Leu Pro Gln Leu Leu Trp Asp Ile
85 90 95Thr Tyr Arg Phe Gln Gly Pro Asp Leu Leu Cys Arg Ala Val Lys Tyr
100 105 110Leu Gln Val Leu Ser Met Phe Ala Ser Thr Tyr Met Leu Leu Ala Met
115 120 125Thr Leu Asp Arg Tyr Leu Ala Val Cys His Pro Leu Arg Ser Leu Gln
130 135 140Gln Pro Gly Gln Ser Thr Tyr Leu Leu Ile Ala Ala Pro Trp Leu Leu145 150 155 160Ala Ala Ile Phe Ser Leu Pro Gln Val Phe Ile Phe Ser Leu Arg Glu
165 170 175Val Ile Gln Gly Ser Gly Val Leu Asp Cys Trp Ala Asp Phe Gly Phe
180 185 190Pro Trp Gly Pro Arg Ala Tyr Leu Thr Trp Thr Thr Leu Ala Ile Phe
195 200 205Val Leu Pro Val Thr Met Leu Thr Ala Cys Tyr Ser Leu Ile Cys His
210 215 220Glu Ile Cys Lys Asn Leu Lys Val Lys Thr Gln Ala Trp Arg Val Gly225 230 235 240Gly Gly Gly Trp Arg Thr Trp Asp Arg Pro Ser Pro Ser Thr Leu Ala
245 250 255Ala Thr Thr Arg Gly Leu Pro Ser Arg Val Ser Ser Ile Asn Thr Ile
260 265 270Ser Arg Ala Lys Ile Arg Thr Lys Lys Met Thr Phe Val Ile Val Leu
275 280 285Ala Tyr Ile Ala Cys Trp Ala Pro Phe Phe Ser Val Gln Met Trp Ser
290 295 300Val Trp Asp Lys Asn Ala Pro Asp Glu Asp Ser Thr Asn Val Ala Phe305 310 315 320Thr Ile Ser Met Leu Leu Gly Asn Leu Asn Ser Cys Cys Asn Pro Trp
325 330 335Ile Tyr Met Gly Phe Asn Ser His Leu Leu Pro Arg Pro Leu Arg His
340 345 350Leu Ala Cys Cys Gly Gly Pro Gln Pro Arg Met Arg Arg Arg Leu Ser
355 360 365Asp Gly Ser Leu Ser Ser Arg His Thr Thr Leu Leu Thr Arg Ser Ser
370 375 380Cys Pro Ala Thr Leu Ser Leu Ser Leu Ser Leu Thr Leu Ser Gly Arg385 390 395 400Pro Arg Pro Glu Glu Ser Pro Arg Asp Leu Glu Leu Ala Asp Gly Glu
405 410 415Gly Thr Ala Glu Thr Ile Ile Phe
420<210>456<211>1116<212>DNA<213>智人(Homo sapiens)<400>456atgctcatgg cgtccaccac ttccgctgtg cctgggcatc cctctctgcc cagcctgccc 60agcaacagca gccaggagag gccactggac acccgggacc cgctgctagc ccgggcggag 120ctggcgctgc tctccatagt ctttgtggct gtggccctga gcaatggcct ggtgctggcg 180gccctagctc ggcggggccg gcggggccac tgggcaccca tacacgtctt cattggccac 240ttgtgcctgg ccgacctggc cgtggctctg ttccaagtgc tgccccagct ggcctggaag 300gccaccgacc gcttccgtgg gccagatgcc ctgtgtcggg ccgtgaagta tctgcagatg 360gtgggcatgt atgcctcctc ctacatgatc ctggccatga cgctggaccg ccaccgtgcc 420atctgccgtc ccatgctggc gtaccgccat ggaagtgggg ctcactggaa ccggccggtg 480ctagtggctt gggccttctc gctccttctc agcctgcccc agctcttcat cttcgcccag 540cgcaacgtgg aaggtggcag cggggtcact gactgctggg cctgctttgc ggagccctgg 600ggccgtcgca cctatgtcac ctggattgcc ctgatggtgt tcgtggcacc taccctgggt 660atcgccgcct gccaggtgct catcttccgg gagattcatg ccagtctggt gccagggcca 720tcagagaggc ctggggggcg ccgcagggga cgccggacag gcagccccgg tgagggagcc 780cacgtgtcag cagctgtggc caagactaag aggatgacgc tagtgattgt ggtcgtctat 840gtgctgtgct gggcaccctt cttcctggtg cagctgtggg ccgcgtggga cccggaggca 900cctctggaag gggcgccctt tgtgctactc atgttgctgg ccagcctcaa cagctgcacc 960aacccctgga tctatgcatc tttcagcagc agcgtgtcct cagagctgcg aagcttgctc 1020tgctgtgccc ggggacgcac cccacccagc ctgggtcccc aagatgagtc ctgcaccacc 1080gccagctcct ccctggccaa ggacacttca tcgtga 1116<210>457<211>371<212>PRT<213>智人(Homo sapiens)<400>457Met Leu Met Ala Ser Thr Thr Ser Ala Val Pro Gly His Pro Ser Leu1 5 10 15Pro Ser Leu Pro Ser Asn Ser Ser Gln Glu Arg Pro Leu Asp Thr Arg
20 25 30Asp Pro Leu Leu Ala Arg Ala Glu Leu Ala Leu Leu Ser Ile Val Phe
35 40 45Val Ala Val Ala Leu Ser Asn Gly Leu Val Leu Ala Ala Leu Ala Arg
50 55 60Arg Gly Arg Arg Gly His Trp Ala Pro Ile His Val Phe Ile Gly His65 70 75 80Leu Cys Leu Ala Asp Leu Ala Val Ala Leu Phe Gln Val Leu Pro Gln
85 90 95Leu Ala Trp Lys Ala Thr Asp Arg Phe Arg Gly Pro Asp Ala Leu Cys
100 105 110Arg Ala Val Lys Tyr Leu Gln Met Val Gly Met Tyr Ala Ser Ser Tyr
115 120 125Met Ile Leu Ala Met Thr Leu Asp Arg His Arg Ala Ile Cys Arg Pro
130 135 140Met Leu Ala Tyr Arg His Gly Ser Gly Ala His Trp Asn Arg Pro Val145 150 155 160Leu Val Ala Trp Ala Phe Ser Leu Leu Leu Ser Leu Pro Gln Leu Phe
165 170 175Ile Phe Ala Gln Arg Asn Val Glu Gly Gly Ser Gly Val Thr Asp Cys
180 185 190Trp Ala Cys Phe Ala Glu Pro Trp Gly Arg Arg Thr Tyr Val Thr Trp
195 200 205Ile Ala Leu Met Val Phe Val Ala Pro Thr Leu Gly Ile Ala Ala Cys
210 215 220Gln Val Leu Ile Phe Arg Glu Ile His Ala Ser Leu Val Pro Gly Pro225 230 235 240Ser Glu Arg Pro Gly Gly Arg Arg Arg Gly Arg Arg Thr Gly Ser Pro
245 250 255Gly Glu Gly Ala His Val Ser Ala Ala Val Ala Lys Thr Lys Arg Met
260 265 270Thr Leu Val Ile Val Val Val Tyr Val Leu Cys Trp Ala Pro Phe Phe
275 280 285Leu Val Gln Leu Trp Ala Ala Trp Asp Pro Glu Ala Pro Leu Glu Gly
290 295 300Ala Pro Phe Val Leu Leu Met Leu Leu Ala Ser Leu Asn Ser Cys Thr305 310 315 320Asn Pro Trp Ile Tyr Ala Ser Phe Ser Ser Ser Val Ser Ser Glu Leu
325 330 335Arg Ser Leu Leu Cys Cys Ala Arg Gly Arg Thr Pro Pro Ser Leu Gly
340 345 350Pro Gln Asp Glu Ser Cys Thr Thr Ala Ser Ser Ser Leu Ala Lys Asp
355 360 365Thr Ser Ser
370<210>458<211>1200<212>DNA<213>智人(Homo sapiens)<400>458atggctcaaa ggcagcctca ctcacctaat cagactttaa tttcaatcac aaatgacaca 60gaatcatcaa gctctgtggt ttctaacgat aacacaaata aaggatggag cggggacaac 120tctccaggaa tagaagcatt gtgtgccatc tatattactt atgctgtgat catttcagtg 180ggcatccttg gaaatgctat tctcatcaaa gtctttttca agaccaaatc catgcaaaca 240gttccaaata ttttcatcac cagcctggct tttggagatc ttttacttct gctaacttgt 300gtgccagtgg atgcaactca ctaccttgca gaaggatggc tgttcggaag aattggttgt 360aaggtgctct ctttcatccg gctcacttct gttggtgtgt cagtgttcac attaacaatt 420ctcagcgctg acagatacaa ggcagttgtg aagccacttg agcgacagcc ctccaatgcc 480atcctgaaga cttgtgtaaa agctggctgc gtctggatcg tgtctatgat atttgctcta 540cctgaggcta tattttcaaa tgtatacact tttcgagatc ccaataaaaa tatgacattt 600gaatcatgta cctcttatcc tgtctctaag aagctcttgc aagaaataca ttctctgctg 660tgcttcttag tgttctacat tattccactc tctattatct ctgtctacta ttccttgatt 720gctaggaccc tttacaaaag caccctgaac atacctactg aggaacaaag ccatgcccgt 780aagcagattg aatcccgaaa gagaattaaa agaacggtat tggtgttggt ggctctgttt 840gccctctgct ggttgccaaa tcacctcctg tacctctacc attcattcac ttctcaaacc 900tatgtagacc cctctgccat gcatttcatt ttcaccattt tctctcgggt tttggctttc 960agcaattctt gcgtaaaccc ctttgctctc tactggctga gcaaaagctt ccagaagcat 1020tttaaagctc agttgttctg ttgcaaggcg gagcggcctg agcctcctgt tgctgacacc 1080tctcttacca ccctggctgt gatgggaacg gtcccgggca ctgggagcat acagatgtct 1140gaaattagtg tgacctcgtt cactgggtgt agtgtgaagc aggcagagga cagattctag 1200<210>459<211>399<212>PRT<213>智人(Homo sapiens)<400>459Met Ala Gln Arg Gln Pro His Ser Pro Asn Gln Thr Leu Ile Ser Ile1 5 10 15Thr Asn Asp Thr Glu Ser Ser Ser Ser Val Val Ser Asn Asp Asn Thr
20 25 30Asn Lys Gly Trp Ser Gly Asp Asn Ser Pro Gly Ile Glu Ala Leu Cys
35 40 45Ala Ile Tyr Ile Thr Tyr Ala Val Ile Ile Ser Val Gly Ile Leu Gly
50 55 60Asn Ala Ile Leu Ile Lys Val Phe Phe Lys Thr Lys Ser Met Gln Thr65 70 75 80Val Pro Asn Ile Phe Ile Thr Ser Leu Ala Phe Gly Asp Leu Leu Leu
85 90 95Leu Leu Thr Cys Val Pro Val Asp Ala Thr His Tyr Leu Ala Glu Gly
100 105 110Trp Leu Phe Gly Arg Ile Gly Cys Lys Val Leu Ser Phe Ile Arg Leu
115 120 125Thr Ser Val Gly Val Ser Val Phe Thr Leu Thr Ile Leu Ser Ala Asp
130 135 140Arg Tyr Lys Ala Val Val Lys Pro Leu Glu Arg Gln Pro Ser Asn Ala145 150 155 160Ile Leu Lys Thr Cys Val Lys Ala Gly Cys Val Trp Ile Val Ser Met
165 170 175Ile Phe Ala Leu Pro Glu Ala Ile Phe Ser Asn Val Tyr Thr Phe Arg
180 185 190Asp Pro Asn Lys Asn Met Thr Phe Glu Ser Cys Thr Ser Tyr Pro Val
195 200 205Ser Lys Lys Leu Leu Gln Glu Ile His Ser Leu Leu Cys Phe Leu Val
210 215 220Phe Tyr Ile Ile Pro Leu Ser Ile Ile Ser Val Tyr Tyr Ser Leu Ile225 230 235 240Ala Arg Thr Leu Tyr Lys Ser Thr Leu Asn Ile Pro Thr Glu Glu Gln
245 250 255Ser His Ala Arg Lys Gln Ile Glu Ser Arg Lys Arg Ile Lys Arg Thr
260 265 270Val Leu Val Leu Val Ala Leu Phe Ala Leu Cys Trp Leu Pro Asn His
275 280 285Leu Leu Tyr Leu Tyr His Ser Phe Thr Ser Gln Thr Tyr Val Asp Pro
290 295 300Ser Ala Met His Phe Ile Phe Thr Ile Phe Ser Arg Val Leu Ala Phe305 310 315 320Ser Asn Ser Cys Val Asn Pro Phe Ala Leu Tyr Trp Leu Ser Lys Ser
325 330 335Phe Gln Lys His Phe Lys Ala Gln Leu Phe Cys Cys Lys Ala Glu Arg
340 345 350Pro Glu Pro Pro Val Ala Asp Thr Ser Leu Thr Thr Leu Ala Val Met
355 360 365Gly Thr Val Pro Gly Thr Gly Ser Ile Gln Met Ser Glu Ile Ser Val
370 375 380Thr Ser Phe Thr Gly Cys Ser Val Lys Gln Ala Glu Asp Arg Phe385 390 395<210>460<211>1062<212>DNA<213>智人(Homo sapiens)<400>460atggcatcat cctggccccc tctagagctc caatcctcca accagagcca gctcttccct 60caaaatgcta cggcctgtga caatgctcca gaagcctggg acctgctgca cagagtgctg 120ccgacattta tcatctccat ctgtttcttc ggcctcctag ggaaccttLt tgtcctgttg 180gtcttcctcc tgccccggcg gcaactgaac gtggcagaaa tctacctggc caacctggca 240gcctctgatc tggtgtttgt cttgggcttg cccttctggg cagagaatat ctggaaccag 300tttaactggc ctttcggagc cctcctctgc cgtgtcatca acggggtcat caaggccaat 360ttgttcatca gcatcttcct ggtggtggcc atcagccagg accgctaccg cgtgctggtg 420caccctatgg ccagccggag gcagcagcgg cggaggcagg cccgggtcac ctgcgtgctc 480atctgggttg tggggggcct cttgagcatc cccacattcc tgctgcgatc catccaagcc 540gtcccagatc tgaacatcac cgcctgcatc ctgctcctcc cccatgaggc ctggcacttt 600gcaaggattg tggagttaaa tattctgggt ttcctcctac cactggctgc gatcgtcttc 660ttcaactacc acatcctggc ctccctgcga acgcgggagg aggtcagcag gacaaggtgc 720gggggccgca aggatagcaa gaccaaagcg ctgatcctca cgctcgtggt tgccttcctg 780gtctgctggg ccccttacca cttctttgcc ttcctggaat tcttattcca ggtgcaagca 840gtccgaggct gcttttggga ggacttcatt gacctgggcc tgcaattggc caacttcttt 900gccttcacta acagctccct gaatccagta atttatgtct ttgtgggccg gctcttcagg 960accaaggtct gggaacttta taaacaatgc acccctaaaa gtcttgctcc aatatcttca 1020tcccatagga aagaaatctt ccaacttttc tggcggaatt aa 1062<210>461<211>353<212>PRT<213>智人(Homo sapiens)<400>461Met Ala Ser Ser Trp Pro Pro Leu Glu Leu Gln Ser Ser Asn Gln Ser1 5 10 15Gln Leu Phe Pro Gln Asn Ala Thr Ala Cys Asp Asn Ala Pro Glu Ala
20 25 30Trp Asp Leu Leu His Arg Val Leu Pro Thr Phe Ile Ile Ser Ile Cys
35 40 45Phe Phe Gly Leu Leu Gly Asn Leu Phe Val Leu Leu Val Phe Leu Leu
50 55 60Pro Arg Arg Gln Leu Asn Val Ala Glu Ile Tyr Leu Ala Asn Leu Ala65 70 75 80Ala Ser Asp Leu Val Phe Val Leu Gly Leu Pro Phe Trp Ala Glu Asn
85 90 95Ile Trp Asn Gln Phe Asn Trp Pro Phe Gly Ala Leu Leu Cys Arg Val
100 105 110Ile Asn Gly Val Ile Lys Ala Asn Leu Phe Ile Ser Ile Phe Leu Val
115 120 125Val Ala Ile Ser Gln Asp Arg Tyr Arg Val Leu Val His Pro Met Ala
130 135 140Ser Arg Arg Gln Gln Arg Arg Arg Gln Ala Arg Val Thr Cys Val Leu145 150 155 160Ile Trp Val Val Gly Gly Leu Leu Ser Ile Pro Thr Phe Leu Leu Arg
165 170 175Ser Ile Gln Ala Val Pro Asp Leu Asn Ile Thr Ala Cys Ile Leu Leu
180 185 190Leu Pro His Glu Ala Trp His Phe Ala Arg Ile Val Glu Leu Asn Ile
195 200 205Leu Gly Phe Leu Leu Pro Leu Ala Ala Ile Val Phe Phe Asn Tyr His
210 215 220Ile Leu Ala Ser Leu Arg Thr Arg Glu Glu Val Ser Arg Thr Arg Cys225 230 235 240Gly Gly Arg Lys Asp Ser Lys Thr Lys Ala Leu Ile Leu Thr Leu Val
245 250 255Val Ala Phe Leu Val Cys Trp Ala Pro Tyr His Phe Phe Ala Phe Leu
260 265 270Glu Phe Leu Phe Gln Val Gln Ala Val Arg Gly Cys Phe Trp Glu Asp
275 280 285Phe Ile Asp Leu Gly Leu Gln Leu Ala Asn Phe Phe Ala Phe Thr Asn
290 295 300Ser Ser Leu Asn Pro Val Ile Tyr Val Phe Val Gly Arg Leu Phe Arg305 310 315 320Thr Lys Val Trp Glu Leu Tyr Lys Gln Cys Thr Pro Lys Ser Leu Ala
325 330 335Pro Ile Ser Ser Ser His Arg Lys Glu Ile Phe Gln Leu Phe Trp Arg
340 345 350Asn<210>462<211>1176<212>DNA<213>智人(Homo sapiens)<400>462atgttctctc cctggaagat atcaatgttt ctgtctgttc gtgaggactc cgtgcccacc 60acggcctctt tcagcgccga catgctcaat gtcaccttgc aagggcccac tcttaacggg 120acctttgccc agagcaaatg cccccaagtg gagtggctgg gctggctcaa caccatccag 180ccccccttcc tctgggtgct gttcgtgctg gccaccctag agaacatctt tgtcctcagc 240gtcttctgcc tgcacaagag cagctgcacg gtggcagaga tctacctggg gaacctggcc 300gcagcagacc tgatcctggc ctgcgggctg cccttctggg ccatcaccat ctccaacaac 360ttcgactggc tctttgggga gacgctctgc cgcgtggtga atgccattat ctccatgaac 420ctgtacagca gcatctgttt cctgatgctg gtgagcatcg accgctacct ggccctggtg 480aaaaccatgt ccatgggccg gatgcgcggc gtgcgctggg ccaagctcta cagcttggtg 540atctgggggt gtacgctgct cctgagctca cccatgctgg tgttccggac catgaaggag 600tacagcgatg agggccacaa cgtcaccgct tgtgtcatca gctacccatc cctcatctgg 660gaagtgttca ccaacatgct cctgaatgtc gtgggcttcc tgctgcccct gagtgtcatc 720accttctgca cgatgcagat catgcaggtg ctgcggaaca acgagatgca gaagttcaag 780gagatccaga cggagaggag ggccaaggtg ctagtcctgg ttgtgctgct gctattcatc 840atctgctggc tgcccttcca gatcagcacc ttcctggata cgctgcatcg cctcggcatc 900ctctccagct gccaggacga gcgcatcatc gatgtaatca cacagatcgc ctccttcatg 960gcctacagca acagctgcct caacccactg gtgtacgtga tcgtgggcaa gcgcttccga 1020aagaagtctt gggaggtgta ccagggagtg tgccagaaag ggggctgcag gtcagaaccc 1080attcagatgg agaactccat gggcacactg cggacctcca tctccgtgga acgccagatt 1140cacaaactgc aggactgggc agggagcaga cagtga 1176<210>463<211>391<212>PRT<213>智人(Homo sapiens)<400>463Met Phe Ser Pro Trp Lys Ile Ser Met Phe Leu Ser Val Arg Glu Asp1 5 10 15Ser Val Pro Thr Thr Ala Ser Phe Ser Ala Asp Met Leu Asn Val Thr
20 25 30Leu Gln Gly Pro Thr Leu Asn Gly Thr Phe Ala Gln Ser Lys Cys Pro
35 40 45Gln Val Glu Trp Leu Gly Trp Leu Asn Thr Ile Gln Pro Pro Phe Leu
50 55 60Trp Val Leu Phe Val Leu Ala Thr Leu Glu Asn Ile Phe Val Leu Ser65 70 75 80Val Phe Cys Leu His Lys Ser Ser Cys Thr Val Ala Glu Ile Tyr Leu
85 90 95Gly Asn Leu Ala Ala Ala Asp Leu Ile Leu Ala Cys Gly Leu Pro Phe
100 105 110Trp Ala Ile Thr Ile Ser Asn Asn Phe Asp Trp Leu Phe Gly Glu Thr
115 120 125Leu Cys Arg Val Val Asn Ala Ile Ile Ser Met Asn Leu Tyr Ser Ser
130 135 140Ile Cys Phe Leu Met Leu Val Ser Ile Asp Arg Tyr Leu Ala Leu Val145 150 155 160Lys Thr Met Ser Met Gly Arg Met Arg Gly Val Arg Trp Ala Lys Leu
165 170 175Tyr Ser Leu Val Ile Trp Gly Cys Thr Leu Leu Leu Ser Ser Pro Met
180 185 190Leu Val Phe Arg Thr Met Lys Glu Tyr Ser Asp Glu Gly His Asn Val
195 200 205Thr Ala Cys Val Ile Ser Tyr Pro Ser Leu Ile Trp Glu Val Phe Thr
210 215 220Asn Met Leu Leu Asn Val Val Gly Phe Leu Leu Pro Leu Ser Val Ile225 230 235 240Thr Phe Cys Thr Met Gln Ile Met Gln Val Leu Arg Asn Asn Glu Met
245 250 255Gln Lys Phe Lys Glu Ile Gln Thr Glu Arg Arg Ala Lys Val Leu Val
260 265 270Leu Val Val Leu Leu Leu Phe Ile Ile Cys Trp Leu Pro Phe Gln Ile
275 280 285Ser Thr Phe Leu Asp Thr Leu His Arg Leu Gly Ile Leu Ser Ser Cys
290 295 300Gln Asp Glu Arg Ile Ile Asp Val Ile Thr Gln Ile Ala Ser Phe Met305 310 315 320Ala Tyr Ser Asn Ser Cys Leu Asn Pro Leu Val Tyr Val Ile Val Gly
325 330 335Lys Arg Phe Arg Lys Lys Ser Trp Glu Val Tyr Gln Gly Val Cys Gln
340 345 350Lys Gly Gly Cys Arg Ser Glu Pro Ile Gln Met Glu Asn Ser Met Gly
355 360 365Thr Leu Arg Thr Ser Ile Ser Val Glu Arg Gln Ile His Lys Leu Gln
370 375 380Asp Trp Ala Gly Ser Arg Gln385 390<210>464<211>1449<212>DNA<213>智人(Homo sapiens)<400>464atggcgtctt tctctgctga gaccaattca actgacctac tctcacagcc atggaatgag 60cccccagtaa ttctctccat ggtcattctc agccttactt ttttactggg attgccaggc 120aatgggctgg tgctgtgggt ggctggcctg aagatgcagc ggacagtgaa cacaatttgg 180ttcctccacc tcaccttggc ggacctcctc tgctgcctct ccttgccctt ctcgctggct 240cacttggctc tccagggaca gtggccctac ggcaggttcc tatgcaagct catcccctcc 300atcattgtcc tcaacatgtt tgccagtgtc ttcctgctta ctgccattag cctggatcgc 360tgtcttgtgg tattcaagcc aatctggtgt cagaatcatc gcaatgtagg gatggcctgc 420tctatctgtg gatgtatctg ggtggtggct tgtgtgatgt gcattcctgt gttcgtgtac 480cgggaaatct tcactacaga caaccataat agatgtggct acaaatttgg tctctccagc 540tcattagatt atccagactt ttatggagat ccactagaaa acaggtctct tgaaaacatt 600gttcagccgc ctggagaaat gaatgatagg ttagatcctt cctctttcca aacaaatgat 660catccttgga cagtccccac tgtcttccaa cctcaaacat ttcaaagacc ttctgcagat 720tcactcccta ggggttctgc taggttaaca agtcaaaatc tgtattctaa tgtatttaaa 780cctgctgatg tggtctcacc taaaatcccc agtgggtttc ctattgaaga tcacgaaacc 840agcccactgg ataactctga tgcttttctc tctactcatt taaagctgtt ccctagcgct 900tctagcaatt ccttctacga gtctgagcta ccacaaggtt tccaggatta ttacaattta 960ggccaattca cagatgacga tcaagtgcca acacccctcg tggcaataac gatcactagg 1020ctagtggtgg gtttcctgct gccctctgtt atcatgatag cctgttacag cttcattgtc 1080ttccgaatgc aaaggggccg cttcgccaag tctcagagca aaaccaagcg agtggccgtg 1140gtggtggtgg ctgtctttct tgtctgctgg actccatacc acatttttgg agtcctgtca 1200ttgcttactg acccagaaac tcccttgggg aaaactctga tgtcctggga tcatgtatgc 1260attgctctag catctgccaa tagttgcttt aatcccttcc tttatgccct cttggggaaa 1320gattttagga agaaagcaag gcagtccatt cagggaattc tggaggcagc cttcagtgag 1380gagctcacac gttccaccca ctgtccctca aacaatgtca tttcagaaag aaatagtaca 1440actgtgtga 1449<210>465<211>482<212>PRT<213>智人(Homo sapiens)<400>465Met Ala Ser Phe Ser Ala Glu Thr Asn Ser Thr Asp Leu Leu Ser Gln1 5 10 15Pro Trp Asn Glu Pro Pro Val Ile Leu Ser Met Val Ile Leu Ser Leu
20 25 30Thr Phe Leu Leu Gly Leu Pro Gly Asn Gly Leu Val Leu Trp Val Ala
35 40 45Gly Leu Lys Met Gln Arg Thr Val Asn Thr Ile Trp Phe Leu His Leu
50 55 60Thr Leu Ala Asp Leu Leu Cys Cys Leu Ser Leu Pro Phe Ser Leu Ala65 70 75 80His Leu Ala Leu Gln Gly Gln Trp Pro Tyr Gly Arg Phe Leu Cys Lys
85 90 95Leu Ile Pro Ser Ile Ile Val Leu Asn Met Phe Ala Ser Val Phe Leu
100 105 110Leu Thr Ala Ile Ser Leu Asp Arg Cys Leu Val Val Phe Lys Pro Ile
115 120 125Trp Cys Gln Asn His Arg Asn Val Gly Met Ala Cys Ser Ile Cys Gly
130 135 140Cys Ile Trp Val Val Ala Cys Val Met Cys Ile Pro Val Phe Val Tyr145 150 155 160Arg Glu Ile Phe Thr Thr Asp Asn His Asn Arg Cys Gly Tyr Lys Phe
165 170 175Gly Leu Ser Ser Ser Leu Asp Tyr Pro Asp Phe Tyr Gly Asp Pro Leu
180 185 190Glu Asn Arg Ser Leu Glu Asn Ile Val Gln Pro Pro Gly Glu Met Asn
195 200 205Asp Arg Leu Asp Pro Ser Ser Phe Gln Thr Asn Asp His Pro Trp Thr
210 215 220Val Pro Thr Val Phe Gln Pro Gln Thr Phe Gln Arg Pro Ser Ala Asp225 230 235 240Ser Leu Pro Arg Gly Ser Ala Arg Leu Thr Ser Gln Asn Leu Tyr Ser
245 250 255Asn Val Phe Lys Pro Ala Asp Val Val Ser Pro Lys Ile Pro Ser Gly
260 265 270Phe Pro Ile Glu Asp His Glu Thr Ser Pro Leu Asp Asn Ser Asp Ala
275 280 285Phe Leu Ser Thr His Leu Lys Leu Phe Pro Ser Ala Ser Ser Asn Ser
290 295 300Phe Tyr Glu Ser Glu Leu Pro Gln Gly Phe Gln Asp Tyr Tyr Asn Leu305 310 315 320Gly Gln Phe Thr Asp Asp Asp Gln Val Pro Thr Pro Leu Val Ala Ile
325 330 335Thr Ile Thr Arg Leu Val Val Gly Phe Leu Leu Pro Ser Val Ile Met
340 345 350Ile Ala Cys Tyr Ser Phe Ile Val Phe Arg Met Gln Arg Gly Arg Phe
355 360 365Ala Lys Ser Gln Ser Lys Thr Lys Arg Val Ala Val Val Val Val Ala
370 375 380Val Phe Leu Val Cys Trp Thr Pro Tyr His Ile Phe Gly Val Leu Ser385 390 395 400Leu Leu Thr Asp Pro Glu Thr Pro Leu Gly Lys Thr Leu Met Ser Trp
405 410 415Asp His Val Cys Ile Ala Leu Ala Ser Ala Asn Ser Cys Phe Asn Pro
420 425 430Phe Leu Tyr Ala Leu Leu Gly Lys Asp Phe Arg Lys Lys Ala Arg Gln
435 440 445Ser Ile Gln Gly Ile Leu Glu Ala Ala Phe Ser Glu Glu Leu Thr Arg
450 455 460Ser Thr His Cys Pro Ser Asn Asn Val Ile Ser Glu Arg Asn Ser Thr465 470 475 480Thr Val<210>466<211>1053<212>DNA<213>智人(Homo sapiens)<400>466atgaactcct tcaattatac cacccctgat tatgggcact atgatgacaa ggataccctg 60gacctcaaca cccctgtgga taaaacttct aacacgctgc gtgttccaga catcctggcc 120ttggtcatct ttgcagtcgt cttcctggtg ggagtgctgg gcaatgccct ggtggtctgg 180gtgacggcat tcgaggccaa gcggaccatc aatgccatct ggttcctcaa cttggcggta 240gccgacttcc tctcctgcct ggcgctgccc atcttgttca cgtccattgt acagcatcac 300cactggccct ttggcggggc cgcctgcagc atcctgccct ccctcatcct gctcaacatg 360tacgccagca tcctgctcct ggccaccatc agcgccgacc gctttctgct ggtgtttaaa 420cccatctggt gccagaactt ccgaggggcc ggcttggcct ggatcgcctg tgccgtggct 480tggggtttag ccctgctgct gaccataccc tccttcctgt accgggtggt ccgggaggag 540tactttccac caaaggtgtt gtgtggcgtg gactacagcc acgacaaacg gcgggagcga 600gccgtggcca tcgtccggct ggtcctgggc ttcctgtggc ctctactcac gctcacgatt 660tgttacactt tcatcctgct ccggacgtgg agccgcaggg ccacgcggtc caccaagaca 720aagaaggtgg tggtggcagt ggtggccagt ttctttatct tctggttgcc ctaccaggtg 780acggggataa tgatgtcctt cctggagcca tcgtcaccca ccttcctgct gctgaataag 840ctggactccc tgtgtgtctc ctttgcctac atcaactgct gcatcaaccc catcatctac 900gtggtggccg gccagggctt ccagggccga ctgcggaaat ccctccccag cctcctccgg 960aacgtgttga ctgaagagtc cgtggttagg gagagcaagt cattcacgcg ctccacagtg 1020gacactatgg cccagaagac ccaggcagtg tag 1053<210>467<211>350<212>PRT<213>智人(Homo sapiens)<400>467Met Asn Ser Phe Asn Tyr Thr Thr Pro Asp Tyr Gly His Tyr Asp Asp1 5 10 15Lys Asp Thr Leu Asp Leu Asn Thr Pro Val Asp Lys Thr Ser Asn Thr
20 25 30Leu Arg Val Pro Asp Ile Leu Ala Leu Val Ile Phe Ala Val Val Phe
35 40 45Leu Val Gly Val Leu Gly Asn Ala Leu Val Val Trp Val Thr Ala Phe
50 55 60Glu Ala Lys Arg Thr Ile Asn Ala Ile Trp Phe Leu Asn Leu Ala Val65 70 75 80Ala Asp Phe Leu Ser Cys Leu Ala Leu Pro Ile Leu Phe Thr Ser Ile
85 90 95Val Gln His His His Trp Pro Phe Gly Gly Ala Ala Cys Ser Ile Leu
100 105 110Pro Ser Leu Ile Leu Leu Asn Met Tyr Ala Ser Ile Leu Leu Leu Ala
115 120 125Thr Ile Ser Ala Asp Arg Phe Leu Leu Val Phe Lys Pro Ile Trp Cys
130 135 140Gln Asn Phe Arg Gly Ala Gly Leu Ala Trp Ile Ala Cys Ala Val Ala145 150 155 160Trp Gly Leu Ala Leu Leu Leu Thr Ile Pro Ser Phe Leu Tyr Arg Val
165 170 175Val Arg Glu Glu Tyr Phe Pro Pro Lys Val Leu Cys Gly Val Asp Tyr
180 185 190Ser His Asp Lys Arg Arg Glu Arg Ala Val Ala Ile Val Arg Leu Val
195 200 205Leu Gly Phe Leu Trp Pro Leu Leu Thr Leu Thr Ile Cys Tyr Thr Phe
210 215 220Ile Leu Leu Arg Thr Trp Ser Arg Arg Ala Thr Arg Ser Thr Lys Thr225 230 235 240Lys Lys Val Val Val Ala Val Val Ala Ser Phe Phe Ile Phe Trp Leu
245 250 255Pro Tyr Gln Val Thr Gly Ile Met Met Ser Phe Leu Glu Pro Ser Ser
260 265 270Pro Thr Phe Leu Leu Leu Asn Lys Leu Asp Ser Leu Cys Val Ser Phe
275 280 285Ala Tyr Ile Asn Cys Cys Ile Asn Pro Ile Ile Tyr Val Val Ala Gly
290 295 300Gln Gly Phe Gln Gly Arg Leu Arg Lys Ser Leu Pro Ser Leu Leu Arg305 310 315 320Asn Val Leu Thr Glu Glu Ser Val Val Arg Glu Ser Lys Ser Phe Thr
325 330 335Arg Ser Thr Val Asp Thr Met Ala Gln Lys Thr Gln Ala Val
340 345 350<210>468<211>1419<212>DNA<213>智人(Homo sapiens)<400>468atgaagtcga tcctagatgg ccttgcagat accaccttcc gcaccatcac cactgacctc 60ctgtacgtgg gctcaaatga cattcagtac gaagacatca aaggtgacat ggcatccaaa 120ttagggtact tcccacagaa attcccttta acttccttta ggggaagtcc cttccaagag 180aagatgactg cgggagacaa cccccagcta gtcccagcag accaggtgaa cattacagaa 240ttttacaaca agtctctctc gtccttcaag gagaatgagg agaacatcca gtgtggggag 300aacttcatgg acatagagtg tttcatggtc ctgaacccca gccagcagct ggccattgca 360gtcctgtccc tcacgctggg caccttcacg gtcctggaga acctcctggt gctgtgcgtc 420atcctccact cccgcagcct ccgctgcagg ccttcctacc acttcatcgg cagcctggcg 480gtggcagacc tcctggggag tgtcattttt gtctacagct tcattgactt ccacgtgttc 540caccgcaaag atagccgcaa cgtgtttctg ttcaaactgg gtggggtcac ggcctccttc 600actgcctccg tgggcagcct gttcctcaca gccatcgaca ggtacatatc cattcacagg 660cccctggcct ataagaggat tgtcaccagg cccaaggccg tggtagcgtt ttgcctgatg 720tggaccatag ccattgtgat cgccgtgctg cctctcctgg gctggaactg cgagaaactg 780caatctgttt gctcagacat tttcccacac attgatgaaa cctacctgat gttctggatc 840ggggtcacca gcgtactgct tctgttcatc gtgtatgcgt acatgtatat tctctggaag 900gctcacagcc acgccgtccg catgattcag cgtggcaccc agaagagcat catcatccac 960acgtctgagg atgggaaggt acaggtgacc cggccagacc aagcccgcat ggacattagg 1020ttaaagaaga ccctggtcct gatcctggtg gtgttgatca tctgctgggg ccctctgctt 1080gcaatcatgg tgtatgatgt ctttgggaag atgaacaagc tcattaagac ggtgtttgca 1140ttctgcagta tgctctgcct gctgaactcc accgtgaacc ccatcatcta tgctctgagg 1200agtaaggacc tgcgacacgc tttccggagc atgtttccct cttgtgaagg cactgcgcag 1260cctctggata acagcatggg ggactcggac tgcctgcaca aacacgcaaa caatgcagcc 1320agtgttcaca gggccgcaga aagctgcatc aagagcacgg tcaagattgc caaggtaacc 1380atgtctgtgt ccacagacac gtctgccgag gctctgtga 1419<210>469<211>472<212>PRT<213>智人(Homo sapiens)<400>469Met Lys Ser Ile Leu Asp Gly Leu Ala Asp Thr Thr Phe Arg Thr Ile1 5 10 15Thr Thr Asp Leu Leu Tyr Val Gly Ser Asn Asp Ile Gln Tyr Glu Asp
20 25 30Ile Lys Gly Asp Met Ala Ser Lys Leu Gly Tyr Phe Pro Gln Lys Phe
35 40 45Pro Leu Thr Ser Phe Arg Gly Ser Pro Phe Gln Glu Lys Met Thr Ala
50 55 60Gly Asp Asn Pro Gln Leu Val Pro Ala Asp Gln Val Asn Ile Thr Glu65 70 75 80Phe Tyr Asn Lys Ser Leu Ser Ser Phe Lys Glu Asn Glu Glu Asn Ile
85 90 95Gln Cys Gly Glu Asn Phe Met Asp Ile Glu Cys Phe Met Val Leu Asn
100 105 110Pro Ser Gln Gln Leu Ala Ile Ala Val Leu Ser Leu Thr Leu Gly Thr
115 120 125Phe Thr Val Leu Glu Asn Leu Leu Val Leu Cys Val Ile Leu His Ser
130 135 140Arg Ser Leu Arg Cys Arg Pro Ser Tyr His Phe Ile Gly Ser Leu Ala145 150 155 160Val Ala Asp Leu Leu Gly Ser Val Ile Phe Val Tyr Ser Phe Ile Asp
165 170 175Phe His Val Phe His Arg Lys Asp Ser Arg Asn Val Phe Leu Phe Lys
180 185 190Leu Gly Gly Val Thr Ala Ser Phe Thr Ala Ser Val Gly Ser Leu Phe
195 200 205Leu Thr Ala Ile Asp Arg Tyr Ile Ser Ile His Arg Pro Leu Ala Tyr
210 215 220Lys Arg Ile Val Thr Arg Pro Lys Ala Val Val Ala Phe Cys Leu Met225 230 235 240Trp Thr Ile Ala Ile Val Ile Ala Val Leu Pro Leu Leu Gly Trp Asn
245 250 255Cys Glu Lys Leu Gln Ser Val Cys Ser Asp Ile Phe Pro His Ile Asp
260 265 270Glu Thr Tyr Leu Met Phe Trp Ile Gly Val Thr Ser Val Leu Leu Leu
275 280 285Phe Ile Val Tyr Ala Tyr Met Tyr Ile Leu Trp Lys Ala His Ser His
290 295 300Ala Val Arg Met Ile Gln Arg Gly Thr Gln Lys Ser Ile Ile Ile His305 310 315 320Thr Ser Glu Asp Gly Lys Val Gln Val Thr Arg Pro Asp Gln Ala Arg
325 330 335Met Asp Ile Arg Leu Lys Lys Thr Leu Val Leu Ile Leu Val Val Leu
340 345 350Ile Ile Cys Trp Gly Pro Leu Leu Ala Ile Met Val Tyr Asp Val Phe
355 360 365Gly Lys Met Asn Lys Leu Ile Lys Thr Val Phe Ala Phe Cys Ser Met
370 375 380Leu Cys Leu Leu Asn Ser Thr Val Asn Pro Ile Ile Tyr Ala Leu Arg385 390 395 400Ser Lys Asp Leu Arg His Ala Phe Arg Ser Met Phe Pro Ser Cys Glu
405 410 415Gly Thr Ala Gln Pro Leu Asp Asn Ser Met Gly Asp Ser Asp Cys Leu
420 425 430His Lys His Ala Asn Asn Ala Ala Ser Val His Arg Ala Ala Glu Ser
435 440 445Cys Ile Lys Ser Thr Val Lys Ile Ala Lys Val Thr Met Ser Val Ser
450 455 460Thr Asp Thr Ser Ala Glu Ala Leu465 470<210>470<211>1083<212>DNA<213>智人(Homo sapiens)<400>470atggaggaat gctgggtgac agagatagcc aatggctcca aggatggctt ggattccaac 60cctatgaagg attacatgat cctgagtggt ccccagaaga cagctgttgc tgtgttgtgc 120actcttctgg gcctgctaag tgccctggag aacgtggctg tgctctatct gatcctgtcc 180tcccaccaac tccgccggaa gccctcatac ctgttcattg gcagcttggc tggggctgac 240ttcctggcca gtgtggtctt tgcatgcagc tttgtgaatt tccatgtttt ccatggtgtg 300gattccaagg ctgtcttcct gctgaagatt ggcagcgtga ctatgacctt cacagcctct 360gtgggtagcc tcctgctgac cgccattgac cgatacctct gcctgcgcta tccaccttcc 420tacaaagctc tgctcacccg tggaagggca ctggtgaccc tgggcatcat gtgggtcctc 480tcagcactag tctcctacct gcccctcatg ggatggactt gctgtcccag gccctgctct 540gagcttttcc cactgatccc caatgactac ctgctgagct ggctcctgtt catcgccttc 600ctcttttccg gaatcatcta cacctatggg catgttctct ggaaggccca tcagcatgtg 660gccagcttgt ctggccacca ggacaggcag gtgccaggaa tggcccgaat gaggctggat 720gtgaggttga agaagaccct agggctagtg ttggctgtgc tcctcatctg ttggttccca 780gtgctggccc tcatggccca cagcctggcc actacgctca gtgaccaggt caagaaggcc 840tttgctttct gctccatgct gtgcctcatc aactccatgg tcaaccctgt catctatgct 900ctacggagtg gagagatccg ctcctctgcc catcactgcc tggctcactg gaagaagtgt 960gtgaggggcc ttgggtcaga ggcaaaagaa gaagccccga gatcctcagt caccgagaca 1020gaggctgatg ggaaaatcac tccgtggcca gattccagag atctagacct ctctgattgc 1080tga 1083<210>471<211>360<212>PRT<213>智人(Homo sapiens)<400>471Met Glu Glu Cys Trp Val Thr Glu Ile Ala Asn Gly Ser Lys Asp Gly1 5 10 15Leu Asp Ser Asn Pro Met Lys Asp Tyr Met Ile Leu Ser Gly Pro Gln
20 25 30Lys Thr Ala Val Ala Val Leu Cys Thr Leu Leu Gly Leu Leu Ser Ala
35 40 45Leu Glu Asn Val Ala Val Leu Tyr Leu Ile Leu Ser Ser His Gln Leu
50 55 60Arg Arg Lys Pro Ser Tyr Leu Phe Ile Gly Ser Leu Ala Gly Ala Asp65 70 75 80Phe Leu Ala Ser Val Val Phe Ala Cys Ser Phe Val Asn Phe His Val
85 90 95Phe His Gly Val Asp Ser Lys Ala Val Phe Leu Leu Lys Ile Gly Ser
100 105 110Val Thr Met Thr Phe Thr Ala Ser Val Gly Ser Leu Leu Leu Thr Ala
115 120 125Ile Asp Arg Tyr Leu Cys Leu Arg Tyr Pro Pro Ser Tyr Lys Ala Leu
130 135 140Leu Thr Arg Gly Arg Ala Leu Val Thr Leu Gly Ile Met Trp Val Leu145 150 155 160Ser Ala Leu Val Ser Tyr Leu Pro Leu Met Gly Trp Thr Cys Cys Pro
165 170 175Arg Pro Cys Ser Glu Leu Phe Pro Leu Ile Pro Asn Asp Tyr Leu Leu
180 185 190Ser Trp Leu Leu Phe Ile Ala Phe Leu Phe Ser Gly Ile Ile Tyr Thr
195 200 205Tyr Gly His Val Leu Trp Lys Ala His Gln His Val Ala Ser Leu Ser
210 215 220Gly His Gln Asp Arg Gln Val Pro Gly Met Ala Arg Met Arg Leu Asp225 230 235 240Val Arg Leu Lys Lys Thr Leu Gly Leu Val Leu Ala Val Leu Leu Ile
245 250 255Cys Trp Phe Pro Val Leu Ala Leu Met Ala His Ser Leu Ala Thr Thr
260 265 270Leu Ser Asp Gln Val Lys Lys Ala Phe Ala Phe Cys Ser Met Leu Cys
275 280 285Leu Ile Asn Ser Met Val Asn Pro Val Ile Tyr Ala Leu Arg Ser Gly
290 295 300Glu Ile Arg Ser Ser Ala His His Cys Leu Ala His Trp Lys Lys Cys305 310 315 320Val Arg Gly Leu Gly Ser Glu Ala Lys Glu Glu Ala Pro Arg Ser Ser
325 330 335Val Thr Glu Thr Glu Ala Asp Gly Lys Ile Thr Pro Trp Pro Asp Ser
340 345 350Arg Asp Leu Asp Leu Ser Asp Cys
355 360<210>472<211>1083<212>DNA<213>智人(Homo sapiens)<400>472atgctgtcca catctcgttc tcggtttatc agaaatacca acgagagcgg tgaagaagtc 60accacctttt ttgattatga ttacggtgct ccctgtcata aatttgacgt gaagcaaatt 120ggggcccaac tcctgcctcc gctctactcg ctggtgttca tctttggttt tgtgggcaac 180atgctggtcg tcctcatctt aataaactgc aaaaagctga agtgcttgac tgacatttac 240ctgctcaacc tggccatctc tgatctgctt tttcttatta ctctcccatt gtgggctcac 300tctgctgcaa atgagtgggt ctttgggaat gcaatgtgca aattattcac agggctgtat 360cacatcggtt attttggcgg aatcttcttc atcatcctcc tgacaatcga tagatacctg 420gctattgtcc atgctgtgtt tgctttaaaa gccaggacgg tcacctttgg ggtggtgaca 480agtgtgatca cctggttggt ggctgtgttt gcttctgtcc caggaatcat ctttactaaa 540tgccagaaag aagattctgt ttatgtctgt ggcccttatt ttccacgagg atggaataat 600ttccacacaa taatgaggaa cattttgggg ctggtcctgc cgctgctcat catggtcatc 660tgctactcgg gaatcctgaa aaccctgctt cggtgtcgaa acgagaagaa gaggcatagg 720gcaaagagag tcatcttcac catcatgatt gtttactttc tcttctggac tccctataac 780attgtcattc tcctgaacac cttccaggaa ttcttcggcc tgagtaactg tgaaagcacc 840agtcaactgg accaagccac gcaggtgaca gagactcttg ggatgactca ctgctgcatc 900aatcccatca tctatgcctt cgttggggag aagttcagaa ggtatctctc ggtgttcttc 960cgaaagcaca tcaccaagcg cttctgcaaa caatgtccag ttttctacag ggagacagtg 1020gatggagtga cttcaacaaa cacgccttcc actggggagc aggaagtctc ggctggttta 1080taa 1083<210>473<211>360<212>PRT<213>智人(Homo sapiens)<400>473Met Leu Ser Thr Ser Arg Ser Arg Phe Ile Arg Asn Thr Asn Glu Ser1 5 10 15Gly Glu Glu Val Thr Thr Phe Phe Asp Tyr Asp Tyr Gly Ala Pro Cys
20 25 30His Lys Phe Asp Val Lys Gln Ile Gly Ala Gln Leu Leu Pro Pro Leu
35 40 45Tyr Ser Leu Val Phe Ile Phe Gly Phe Val Gly Asn Met Leu Val Val
50 55 60Leu Ile Leu Ile Asn Cys Lys Lys Leu Lys Cys Leu Thr Asp Ile Tyr65 70 75 80Leu Leu Asn Leu Ala Ile Ser Asp Leu Leu Phe Leu Ile Thr Leu Pro
85 90 95Leu Trp Ala His Ser Ala Ala Asn Glu Trp Val Phe Gly Asn Ala Met
100 105 110Cys Lys Leu Phe Thr Gly Leu Tyr His Ile Gly Tyr Phe Gly Gly Ile
115 120 125Phe Phe Ile Ile Leu Leu Thr Ile Asp Arg Tyr Leu Ala Ile Val His
130 135 140Ala Val Phe Ala Leu Lys Ala Arg Thr Val Thr Phe Gly Val Val Thr145 150 155 160Ser Val Ile Thr Trp Leu Val Ala Val Phe Ala Ser Val Pro Gly Ile
165 170 175Ile Phe Thr Lys Cys Gln Lys Glu Asp Ser Val Tyr Val Cys Gly Pro
180 185 190Tyr Phe Pro Arg Gly Trp Asn Asn Phe His Thr Ile Met Arg Asn Ile
195 200 205Leu Gly Leu Val Leu Pro Leu Leu Ile Met Val Ile Cys Tyr Ser Gly
210 215 220Ile Leu Lys Thr Leu Leu Arg Cys Arg Asn Glu Lys Lys Arg His Arg225 230 235 240Ala Lys Arg Val Ile Phe Thr Ile Met Ile Val Tyr Phe Leu Phe Trp
245 250 255Thr Pro Tyr Asn Ile Val Ile Leu Leu Asn Thr Phe Gln Glu Phe Phe
260 265 270Gly Leu Ser Asn Cys Glu Ser Thr Ser Gln Leu Asp Gln Ala Thr Gln
275 280 285Val Thr Glu Thr Leu Gly Met Thr His Cys Cys Ile Asn Pro Ile Ile
290 295 300Tyr Ala Phe Val Gly Glu Lys Phe Arg Arg Tyr Leu Ser Val Phe Phe305 310 315 320Arg Lys His Ile Thr Lys Arg Phe Cys Lys Gln Cys Pro Val Phe Tyr
325 330 335Arg Glu Thr Val Asp Gly Val Thr Ser Thr Asn Thr Pro Ser Thr Gly
340 345 350Glu Gln Glu Val Ser Ala Gly Leu
355 360<210>474<211>1068<212>DNA<213>智人(Homo sapiens)<400>474atgacaacct cactagatac agttgagacc tttggtacca catcctacta tgatgacgtg 60ggcctgctct gtgaaaaagc tgataccaga gcactgatgg cccagtttgt gcccccgctg 120tactccctgg tgttcactgt gggcctcttg ggcaatgtgg tggtggtgat gatcctcata 180aaatacagga ggctccgaat tatgaccaac atctacctgc tcaacctggc catttcggac 240ctgctcttcc tcgtcaccct tccattctgg atccactatg tcagggggca taactgggtt 300tttggccatg gcatgtgtaa gctcctctca gggttttatc acacaggctt gtacagcgag 360atctttttca taatcctgct gacaatcgac aggtacctgg ccattgtcca tgctgtgttt 420gcccttcgag cccggactgt cacttttggt gtcatcacca gcatcgtcac ctggggcctg 480gcagtgctag cagctcttcc tgaatttatc ttctatgaga ctgaagagtt gtttgaagag 540actctttgca gtgctcttta cccagaggat acagtatata gctggaggca tttccacact 600ctgagaatga ccatcttctg tctcgttctc cctctgctcg ttatggccat ctgctacaca 660ggaatcatca aaacgctgct gaggtgcccc agtaaaaaaa agtacaaggc caagcggctc 720atttttgtca tcatggcggt gtttttcatt ttctggacac cctacaatgt ggctatcctt 780ctctcttcct atcaatccat cttatttgga aatgactgtg agcggagcaa gcatctggac 840ctggtcatgc tggtgacaga ggtgatcgcc tactcccact gctgcatgaa cccggtgatc 900tacgcctttg ttggagagag gttccggaag tacctgcgcc acttcttcca caggcacttg 960ctcatgcacc tgggcagata catcccattc cttcctagtg agaagctgga aagaaccagc 1020tctgtctctc catccacagc agagccggaa ctctctattg tgttttag 1068<210>475<211>355<212>PRT<213>智人(Homo sapiens)<400>475Met Thr Thr Ser Leu Asp Thr Val Glu Thr Phe Gly Thr Thr Ser Tyr1 5 10 15Tyr Asp Asp Val Gly Leu Leu Cys Glu Lys Ala Asp Thr Arg Ala Leu
20 25 30Met Ala Gln Phe Val Pro Pro Leu Tyr Ser Leu Val Phe Thr Val Gly
35 40 45Leu Leu Gly Asn Val Val Val Val Met Ile Leu Ile Lys Tyr Arg Arg
50 55 60Leu Arg Ile Met Thr Asn Ile Tyr Leu Leu Asn Leu Ala Ile Ser Asp65 70 75 80Leu Leu Phe Leu Val Thr Leu Pro Phe Trp Ile His Tyr Val Arg Gly
85 90 95His Asn Trp Val Phe Gly His Gly Met Cys Lys Leu Leu Ser Gly Phe
100 105 110Tyr His Thr Gly Leu Tyr Ser Glu Ile Phe Phe Ile Ile Leu Leu Thr
115 120 125Ile Asp Arg Tyr Leu Ala Ile Val His Ala Val Phe Ala Leu Arg Ala
130 135 140Arg Thr Val Thr Phe Gly Val Ile Thr Ser Ile Val Thr Trp Gly Leu145 150 155 160Ala Val Leu Ala Ala Leu Pro Glu Phe Ile Phe Tyr Glu Thr Glu Glu
165 170 175Leu Phe Glu Glu Thr Leu Cys Ser Ala Leu Tyr Pro Glu Asp Thr Val
180 185 190Tyr Ser Trp Arg His Phe His Thr Leu Arg Met Thr Ile Phe Cys Leu
195 200 205Val Leu Pro Leu Leu Val Met Ala Ile Cys Tyr Thr Gly Ile Ile Lys
210 215 220Thr Leu Leu Arg Cys Pro Ser Lys Lys Lys Tyr Lys Ala Lys Arg Leu225 230 235 240Ile Phe Val Ile Met Ala Val Phe Phe Ile Phe Trp Thr Pro Tyr Asn
245 250 255Val Ala Ile Leu Leu Ser Ser Tyr Gln Ser Ile Leu Phe Gly Asn Asp
260 265 270Cys Glu Arg Ser Lys His Leu Asp Leu Val Met Leu Val Thr Glu Val
275 280 285Ile Ala Tyr Ser His Cys Cys Met Asn Pro Val Ile Tyr Ala Phe Val
290 295 300Gly Glu Arg Phe Arg Lys Tyr Leu Arg His Phe Phe His Arg His Leu305 310 315 320Leu Met His Leu Gly Arg Tyr Ile Pro Phe Leu Pro Ser Glu Lys Leu
325 330 335Glu Arg Thr Ser Ser Val Ser Pro Ser Thr Ala Glu Pro Glu Leu Ser
340 345 350Ile Val Phe
355<210>476<211>1059<212>DNA<213>智人(Homo sapiens)<400>476atggattatc aagtgtcaag tccaatctat gacatcaatt attatacatc ggagccctgc 60caaaaaatca atgtgaagca aatcgcagcc cgcctcctgc ctccgctcta ctcactggtg 120ttcatctttg gttttgtggg caacatgctg gtcatcctca tcctgataaa ctgcaaaagg 180ctgaagagca tgactgacat ctacctgctc aacctggcca tctctgacct gtttttcctt 240cttactgtcc ccttctgggc tcactatgct gccgcccagt gggactttgg aaatacaatg 300tgtcaactct tgacagggct ctattttata ggcttcttct ctggaatctt cttcatcatc 360ctcctgacaa tcgataggta cctggctgtc gtccatgctg tgtttgcttt aaaagccagg 420acggtcacct ttggggtggt gacaagtgtg atcacttggg tggtggctgt gtttgcgtct 480ctcccaggaa tcatctttac cagatctcaa aaagaaggtc ttcattacac ctgcagctct 540cattttccat acagtcagta tcaattctgg aagaatttcc agacattaaa gatagtcatc 600ttggggctgg tcctgccgct gcttgtcatg gtcatctgct actcgggaat cctaaaaact 660ctgcttcggt gtcgaaatga gaagaagagg cacagggcta agaggcttat cttcaccatc 720atgattgttt attttctctt ctgggctccc tacaacattg tccttctcct gaacaccttc 780caggaattct ttggcctgaa taattgcagt agctctaaca ggttggacca agctatgcag 840gtgacagaga ctcttgggat gacgcactgc tgcatcaacc ccatcatcta tgcctttgtc 900ggggagaagt tcagaaacta cctcttagtc ttcttccaaa agcacattgc caaacgcttc 960tgcaaatgct gttctatttt ccagcaagag gctcccgagc gagcaagctc agtttacacc 1020cgatccactg gggagcagga aatatctgtg ggcttgtga 1059<210>477<211>352<212>PRT<213>智人(Homo sapiens)<400>477Met Asp Tyr Gln Val Ser Ser Pro Ile Tyr Asp Ile Asn Tyr Tyr Thr1 5 10 15Ser Glu Pro Cys Gln Lys Ile Asn Val Lys Gln Ile Ala Ala Arg Leu
20 25 30Leu Pro Pro Leu Tyr Ser Leu Val Phe Ile Phe Gly Phe Val Gly Asn
35 40 45Met Leu Val Ile Leu Ile Leu Ile Asn Cys Lys Arg Leu Lys Ser Met
50 55 60Thr Asp Ile Tyr Leu Leu Asn Leu Ala Ile Ser Asp Leu Phe Phe Leu65 70 75 80Leu Thr Val Pro Phe Trp Ala His Tyr Ala Ala Ala Gln Trp Asp Phe
85 90 95Gly Asn Thr Met Cys Gln Leu Leu Thr Gly Leu Tyr Phe Ile Gly Phe
100 105 110Phe Ser Gly Ile Phe Phe Ile Ile Leu Leu Thr Ile Asp Arg Tyr Leu
115 120 125Ala Val Val His Ala Val Phe Ala Leu Lys Ala Arg Thr Val Thr Phe
130 135 140Gly Val Val Thr Ser Val Ile Thr Trp Val Val Ala Val Phe Ala Ser145 150 155 160Leu Pro Gly Ile Ile Phe Thr Arg Ser Gln Lys Glu Gly Leu His Tyr
165 170 175Thr Cys Ser Ser His Phe Pro Tyr Ser Gln Tyr Gln Phe Trp Lys Asn
180 185 190Phe Gln Thr Leu Lys Ile Val Ile Leu Gly Leu Val Leu Pro Leu Leu
195 200 205Val Met Val Ile Cys Tyr Ser Gly Ile Leu Lys Thr Leu Leu Arg Cys
210 215 220Arg Asn Glu Lys Lys Arg His Arg Ala Lys Arg Leu Ile Phe Thr Ile225 230 235 240Met Ile Val Tyr Phe Leu Phe Trp Ala Pro Tyr Asn Ile Val Leu Leu
245 250 255Leu Asn Thr Phe Gln Glu Phe Phe Gly Leu Asn Asn Cys Ser Ser Ser
260 265 270Asn Arg Leu Asp Gln Ala Met Gln Val Thr Glu Thr Leu Gly Met Thr
275 280 285His Cys Cys Ile Asn Pro Ile Ile Tyr Ala Phe Val Gly Glu Lys Phe
290 295 300Arg Asn Tyr Leu Leu Val Phe Phe Gln Lys His Ile Ala Lys Arg Phe305 310 315 320Cys Lys Cys Cys Ser Ile Phe Gln Gln Glu Ala Pro Glu Arg Ala Ser
325 330 335Ser Val Tyr Thr Arg Ser Thr Gly Glu Gln Glu Ile Ser Val Gly Leu
340 345 350<210>478<211>1068<212>DNA<213>智人(Homo sapiens)<400>478atggattata cacttgacct cagtgtgaca acagtgaccg actactacta ccctgatatc 60ttctcaagcc cctgtgatgc ggaacttatt cagacaaatg gcaagttgct ccttgctgtc 120ttttattgcc tcctgtttgt attcagtctt ctgggaaaca gcctggtcat cctggtcctt 180gtggtctgca agaagctgag gagcatcaca gatgtatacc tcttgaacct ggccctgtct 240gacctgcttt ttgtcttctc cttccccttt cagacctact atctgctgga ccagtgggtg 300tttgggactg taatgtgcaa agtggtgtct ggcttttatt acattggctt ctacagcagc 360atgtttttca tcaccctcat gagtgtggac aggtacctgg ctgttgtcca tgccgtgtat 420gccctaaagg tgaggacgat caggatgggc acaacgctgt gcctggcagt atggctaacc 480gccattatgg ctaccatccc attgctagtg ttttaccaag tggcctctga agatggtgtt 540ctacagtgtt attcatttta caatcaacag actttgaagt ggaagatctt caccaacttc 600aaaatgaaca ttttaggctt gttgatccca ttcaccatct ttatgttctg ctacattaaa 660atcctgcacc agctgaagag gtgtcaaaac cacaacaaga ccaaggccaa gaggttggtg 720ctcattgtgg tcattgcatc tttacttttc tgggtcccat tcaacgtggt tcttttcctc 780acttccttgc acagtatgca catcttggat ggatgtagca taagccaaca gctgacttat 840gccacccatg tcacagaaat catttccttt actcactgct gtgtgaaccc tgttatctat 900gcttttgttg gggagaagtt caagaaacac ctctcagaaa tatttcagaa aagttgcagc 960caaatcttca actacctagg aagacaaatg cctagggaga gctgtgaaaa gtcatcatcc 1020tgccagcagc actcctcccg ttcctccagc gtagactaca ttttgtga 1068<210>479<211>355<212>PRT<213>智人(Homo sapiens)<400>479Met Asp Tyr Thr Leu Asp Leu Ser Val Thr Thr Val Thr Asp Tyr Tyr1 5 10 15Tyr Pro Asp Ile Phe Ser Ser Pro Cys Asp Ala Glu Leu Ile Gln Thr
20 25 30Asn Gly Lys Leu Leu Leu Ala Val Phe Tyr Cys Leu Leu Phe Val Phe
35 40 45Ser Leu Leu Gly Asn Ser Leu Val Ile Leu Val Leu Val Val Cys Lys
50 55 60Lys Leu Arg Ser Ile Thr Asp Val Tyr Leu Leu Asn Leu Ala Leu Ser65 70 75 80Asp Leu Leu Phe Val Phe Ser Phe Pro Phe Gln Thr Tyr Tyr Leu Leu
85 90 95Asp Gln Trp Val Phe Gly Thr Val Met Cys Lys Val Val Ser Gly Phe
100 105 110Tyr Tyr Ile Gly Phe Tyr Ser Ser Met Phe Phe Ile Thr Leu Met Ser
115 120 125Val Asp Arg Tyr Leu Ala Val Val His Ala Val Tyr Ala Leu Lys Val
130 135 140Arg Thr Ile Arg Met Gly Thr Thr Leu Cys Leu Ala Val Trp Leu Thr145 150 155 160Ala Ile Met Ala Thr Ile Pro Leu Leu Val Phe Tyr Gln Val Ala Ser
165 170 175Glu Asp Gly Val Leu Gln Cys Tyr Ser Phe Tyr Asn Gln Gln Thr Leu
180 185 190Lys Trp Lys Ile Phe Thr Asn Phe Lys Met Asn Ile Leu Gly Leu Leu
195 200 205Ile Pro Phe Thr Ile Phe Met Phe Cys Tyr Ile Lys Ile Leu His Gln
210 215 220Leu Lys Arg Cys Gln Asn His Asn Lys Thr Lys Ala Lys Arg Leu Val225 230 235 240Leu Ile Val Val Ile Ala Ser Leu Leu Phe Trp Val Pro Phe Asn Val
245 250 255Val Leu Phe Leu Thr Ser Leu His Ser Met His Ile Leu Asp Gly Cys
260 265 270Ser Ile Ser Gln Gln Leu Thr Tyr Ala Thr His Val Thr Glu Ile Ile
275 280 285Ser Phe Thr His Cys Cys Val Asn Pro Val Ile Tyr Ala Phe Val Gly
290 295 300Glu Lys Phe Lys Lys His Leu Ser Glu Ile Phe Gln Lys Ser Cys Ser305 310 315 320Gln Ile Phe Asn Tyr Leu Gly Arg Gln Met Pro Arg Glu Ser Cys Glu
325 330 335Lys Ser Ser Ser Cys Gln Gln His Ser Ser Arg Ser Ser Ser Val Asp
340 345 350Tyr Ile Leu
355<210>480<211>1110<212>DNA<213>智人(Homo sapiens)<400>480atgacaccca cagacttcac aagccctatt cctaacatgg ctgatgacta tggctctgaa 60tccacatctt ccatggaaga ctacgttaac ttcaacttca ctgacttcta ctgtgagaaa 120aacaatgtca ggcagtttgc gagccatttc ctcccaccct tgtactggct cgtgttcatc 180gtgggtgcct tgggcaacag tcttgttatc cttgtctact ggtactgcac aagagtgaag 240accatgaccg acatgttcct tttgaatttg gcaattgctg acctcctctt tcttgtcact 300cttcccttct gggccattgc tgctgctgac cagtggaagt tccagacctt catgtgcaag 360gtggtcaaca gcatgtacaa gatgaacttc tacagctgtg tgttgctgat catgtgcatc 420agcgtggaca ggtacattgc cattgcccag gccatgagag cacatacttg gagggagaaa 480aggcttttgt acagcaaaat ggtttgcttt accatctggg tattggcagc tgctctctgc 540atcccagaaa tcttatacag ccaaatcaag gaggaatccg gcattgctat ctgcaccatg 600gtttacccta gcgatgagag caccaaactg aagtcagctg tcttgaccct gaaggtcatt 660ctggggttct tccttccctt cgtggtcatg gcttgctgct ataccatcat cattcacacc 720ctgatacaag ccaagaagtc ttccaagcac aaagccaaaa aagtgaccat cactgtcctg 780accgtctttg tcttgtctca gtttccctac aactgcattt tgttggtgca gaccattgac 840gcctatgcca tgttcatctc caactgtgcc gtttccacca acattgacat ctgcttccag 900gtcacccaga ccatcgcctt cttccacagt tgcctgaacc ctgttctcta tgtttttgtg 960ggtgagagat tccgccggga tctcgtgaaa accctgaaga acttgggttg catcagccag 1020gcccagtggg tttcatttac aaggagagag ggaagcttga agctgtcgtc tatgttgctg 1080gagacaacct caggagcact ctccctctga 1110<210>481<211>369<212>PRT<213>智人(Homo sapiens)<400>481Met Thr Pro Thr Asp Phe Thr Ser Pro Ile Pro Asn Met Ala Asp Asp1 5 10 15Tyr Gly Ser Glu Ser Thr Ser Ser Met Glu Asp Tyr Val Asn Phe Asn
20 25 30Phe Thr Asp Phe Tyr Cys Glu Lys Asn Asn Val Arg Gln Phe Ala Ser
35 40 45His Phe Leu Pro Pro Leu Tyr Trp Leu Val Phe Ile Val Gly Ala Leu
50 55 60Gly Asn Ser Leu Val Ile Leu Val Tyr Trp Tyr Cys Thr Arg Val Lys65 70 75 80Thr Met Thr Asp Met Phe Leu Leu Asn Leu Ala Ile Ala Asp Leu Leu
85 90 95Phe Leu Val Thr Leu Pro Phe Trp Ala Ile Ala Ala Ala Asp Gln Trp
100 105 110Lys Phe Gln Thr Phe Met Cys Lys Val Val Asn Ser Met Tyr Lys Met
115 120 125Asn Phe Tyr Ser Cys Val Leu Leu Ile Met Cys Ile Ser Val Asp Arg
130 135 140Tyr Ile Ala Ile Ala Gln Ala Met Arg Ala His Thr Trp Arg Glu Lys145 150 155 160Arg Leu Leu Tyr Ser Lys Met Val Cys Phe Thr Ile Trp Val Leu Ala
165 170 175Ala Ala Leu Cys Ile Pro Glu Ile Leu Tyr Ser Gln Ile Lys Glu Glu
180 185 190Ser Gly Ile Ala Ile Cys Thr Met Val Tyr Pro Ser Asp Glu Ser Thr
195 200 205Lys Leu Lys Ser Ala Val Leu Thr Leu Lys Val Ile Leu Gly Phe Phe
210 215 220Leu Pro Phe Val Val Met Ala Cys Cys Tyr Thr Ile Ile Ile His Thr225 230 235 240Leu Ile Gln Ala Lys Lys Ser Ser Lys His Lys Ala Lys Lys Val Thr
245 250 255Ile Thr Val Leu Thr Val Phe Val Leu Ser Gln Phe Pro Tyr Asn Cys
260 265 270Ile Leu Leu Val Gln Thr Ile Asp Ala Tyr Ala Met Phe Ile Ser Asn
275 280 285Cys Ala Val Ser Thr Asn Ile Asp Ile Cys Phe Gln Val Thr Gln Thr
290 295 300Ile Ala Phe Phe His Ser Cys Leu Asn Pro Val Leu Tyr Val Phe Val305 310 315 320Gly Glu Arg Phe Arg Arg Asp Leu Val Lys Thr Leu Lys Asn Leu Gly
325 330 335Cys Ile Ser Gln Ala Gln Trp Val Ser Phe Thr Arg Arg Glu Gly Ser
340 345 350Leu Lys Leu Ser Ser Met Leu Leu Glu Thr Thr Ser Gly Ala Leu Ser
355 360 365Leu<210>482<211>1248<212>DNA<213>智人(Homo sapiens)<400>482atgggagggc acccgcagct ccgtctcgtc aaggcccttc tccttctggg gctgaacccc 60gtctctgcct ccctccagga ccagcactgc gagagcctgt ccctggccag caacatctca 120ggactgcagt gcaacgcatc cgtggacctc attggcacct gctggccccg cagccctgcg 180gggcagctag tggttcggcc ctgccctgcc tttttctatg gtgtccgcta caataccaca 240aacaatggct accgggagtg cctggccaat ggcagctggg ccgcccgcgt gaattactcc 300gagtgccagg agatcctcaa tgaggagaaa aaaagcaagg tgcactacca tgtcgcagtc 360atcatcaact acctgggcca ctgtatctcc ctggtggccc tcctggtggc ctttgtcctc 420tttctgcggc tcaggagcat ccggtgcctg cgaaacatca tccactggaa cctcatctcc 480gccttcatcc tgcgcaacgc cacctggttc gtggtccagc taaccatgag ccccgaggtc 540caccagagca acgtgggctg gtgcaggttg gtgacagccg cctacaacta cttccatgtg 600accaacttct tctggatgtt cggcgagggc tgctacctgc acacagccat cgtgctcacc 660tactccactg accggctgcg caaatggatg ttcatctgca ttggctgggg tgtgcccttc 720cccatcattg tggcctgggc cattgggaag ctgtactacg acaatgagaa gtgctggttt 780ggcaaaaggc ctggggtgta caccgactac atctaccagg gccccatgat cctggtcctg 840ctgatcaatt tcatcttcct tttcaacatc gtccgcatcc tcatgaccaa gctccgggca 900tccaccacgt ctgagaccat tcagtacagg aaggctgtga aagcccctct ggtgctgctg 960cccctcctgg gcatcaccta catgctgttc ttcgtcaatc ccggggagga tgaggtctcc 1020cgggtcgtct tcatctactt caactccttc ctggaatcct tccagggctt ctttgtgtct 1080gtgttctact gtttcctcaa tagtgaggtc cgttctgcca tccggaagag gtggcaccgg 1140tggcaggaca agcactcgat ccgtgcccga gtggcccgtg ccatgtccat ccccacctcc 1200ccaacccgtg tcagctttca cagcatcaag cagtccacag cagtctga 1248<210>483<211>415<212>PRT<213>智人(Homo sapiens)<400>483Met Gly Gly His Pro Gln Leu Arg Leu Val Lys Ala Leu Leu Leu Leu1 5 10 15Gly Leu Asn Pro Val Ser Ala Ser Leu Gln Asp Gln His Cys Glu Ser
20 25 30Leu Ser Leu Ala Ser Asn Ile Ser Gly Leu Gln Cys Asn Ala Ser Val
35 40 45Asp Leu Ile Gly Thr Cys Trp Pro Arg Ser Pro Ala Gly Gln Leu Val
50 55 60Val Arg Pro Cys Pro Ala Phe Phe Tyr Gly Val Arg Tyr Asn Thr Thr65 70 75 80Asn Asn Gly Tyr Arg Glu Cys Leu Ala Asn Gly Ser Trp Ala Ala Arg
85 90 95Val Asn Tyr Ser Glu Cys Gln Glu Ile Leu Asn Glu Glu Lys Lys Ser
100 105 ll0Lys Val His Tyr His Val Ala Val Ile Ile Asn Tyr Leu Gly His Cys
115 120 125Ile Ser Leu Val Ala Leu Leu Val Ala Phe Val Leu Phe Leu Arg Leu
130 135 140Arg Ser Ile Arg Cys Leu Arg Asn Ile Ile His Trp Asn Leu Ile Ser145 150 155 160Ala Phe Ile Leu Arg Asn Ala Thr Trp Phe Val Val Gln Leu Thr Met
165 170 175Ser Pro Glu Val His Gln Ser Asn Val Gly Trp Cys Arg Leu Val Thr
180 185 190Ala Ala Tyr Asn Tyr Phe His Val Thr Asn Phe Phe Trp Met Phe Gly
195 200 205Glu Gly Cys Tyr Leu His Thr Ala Ile Val Leu Thr Tyr Ser Thr Asp
210 215 220Arg Leu Arg Lys Trp Met Phe Ile Cys Ile Gly Trp Gly Val Pro Phe225 230 235 240Pro Ile Ile Val Ala Trp Ala Ile Gly Lys Leu Tyr Tyr Asp Asn Glu
245 250 255Lys Cys Trp Phe Gly Lys Arg Pro Gly Val Tyr Thr Asp Tyr Ile Tyr
260 265 270Gln Gly Pro Met Ile Leu Val Leu Leu Ile Asn Phe Ile Phe Leu Phe
275 280 285Asn Ile Val Arg Ile Leu Met Thr Lys Leu Arg Ala Ser Thr Thr Ser
290 295 300Glu Thr Ile Gln Tyr Arg Lys Ala Val Lys Ala Pro Leu Val Leu Leu305 310 315 320Pro Leu Leu Gly Ile Thr Tyr Met Leu Phe Phe Val Asn Pro Gly Glu
325 330 335Asp Glu Val Ser Arg Val Val Phe Ile Tyr Phe Asn Ser Phe Leu Glu
340 345 350Ser Phe Gln Gly Phe Phe Val Ser Val Phe Tyr Cys Phe Leu Asn Ser
355 360 365Glu Val Arg Ser Ala Ile Arg Lys Arg Trp His Arg Trp Gln Asp Lys
370 375 380His Ser Ile Arg Ala Arg Val Ala Arg Ala Met Ser Ile Pro Thr Ser385 390 395 400Pro Thr Arg Val Ser Phe His Ser Ile Lys Gln Ser Thr Ala Val
405 410 415<210>484<211>1059<212>DNA<213>智人(Homo sapiens)<400>484atggagggga tcagtatata cacttcagat aactacaccg aggaaatggg ctcaggggac 60tatgactcca tgaaggaacc ctgtttccgt gaagaaaatg ctaatttcaa taaaatcttc 120ctgcccacca tctactccat catcttctta actggcattg tgggcaatgg attggtcatc 180ctggtcatgg gttaccagaa gaaactgaga agcatgacgg acaagtacag gctgcacctg 240tcagtggccg acctcctctt tgtcatcacg cttcccttct gggcagttga tgccgtggca 300aactggtact ttgggaactt cctatgcaag gcagtccatg tcatctacac agtcaacctc 360tacagcagtg tcctcatcct ggccttcatc agtctggacc gctacctggc catcgtccac 420gccaccaaca gtcagaggcc aaggaagctg ttggctgaaa aggtggtcta tgttggcgtc 480tggatccctg ccctcctgct gactattccc gacttcatct ttgccaacgt cagtgaggca 540gatgacagat atatctgtga ccgcttctac cccaatgact tgtgggtggt tgtgttccag 600tttcagcaca tcatggttgg ccttatcctg cctggtattg tcatcctgtc ctgctattgc 660attatcatct ccaagctgtc acactccaag ggccaccaga agcgcaaggc caagaagacc 720acagtcatcc tcatcctggc tttcttcgcc tgttggctgc cttactacat tgggatcagc 780atcgactcct tcatcctcct ggaaatcatc aagcaagggt gtgagtttga gaacactgtg 840cacaagtgga tttccatcac cgaggcccta gctttcttcc actgttgtct gaaccccatc 900ctctatgctt tccttggagc caaatttaaa acctctgccc agcacgcact cacctctgtg 960agcagagggt ccagcctcaa gatcctctcc aaaggaaagc gaggtggaca ttcatctgtt 1020tccactgagt ctgagtcttc aagttttcac tccagctaa 1059<210>485<211>352<212>PRT<213>智人(Homo sapiens)<400>485Met Glu Gly Ile Ser Ile Tyr Thr Ser Asp Asn Tyr Thr Glu Glu Met1 5 10 15Gly Ser Gly Asp Tyr Asp Ser Met Lys Glu Pro Cys Phe Arg Glu Glu
20 25 30Asn Ala Asn Phe Asn Lys Ile Phe Leu Pro Thr Ile Tyr Ser Ile Ile
35 40 45Phe Leu Thr Gly Ile Val Gly Asn Gly Leu Val Ile Leu Val Met Gly
50 55 60Tyr Gln Lys Lys Leu Arg Ser Met Thr Asp Lys Tyr Arg Leu His Leu65 70 75 80Ser Val Ala Asp Leu Leu Phe Val Ile Thr Leu Pro Phe Trp Ala Val
85 90 95Asp Ala Val Ala Asn Trp Tyr Phe Gly Asn Phe Leu Cys Lys Ala Val
100 105 110His Val Ile Tyr Thr Val Asn Leu Tyr Ser Ser Val Leu Ile Leu Ala
115 120 125Phe Ile Ser Leu Asp Arg Tyr Leu Ala Ile Val His Ala Thr Asn Ser
130 135 140Gln Arg Pro Arg Lys Leu Leu Ala Glu Lys Val Val Tyr Val Gly Val145 150 155 160Trp Ile Pro Ala Leu Leu Leu Thr Ile Pro Asp Phe Ile Phe Ala Asn
165 170 175Val Ser Glu Ala Asp Asp Arg Tyr Ile Cys Asp Arg Phe Tyr Pro Asn
180 185 190Asp Leu Trp Val Val Val Phe Gln Phe Gln His Ile Met Val Gly Leu
195 200 205Ile Leu Pro Gly Ile Val Ile Leu Ser Cys Tyr Cys Ile Ile Ile Ser
210 215 220Lys Leu Ser His Ser Lys Gly His Gln Lys Arg Lys Ala Lys Lys Thr225 230 235 240Thr Val Ile Leu Ile Leu Ala Phe Phe Ala Cys Trp Leu Pro Tyr Tyr
245 250 255Ile Gly Ile Ser Ile Asp Ser Phe Ile Leu Leu Glu Ile Ile Lys Gln
260 265 270Gly Cys Glu Phe Glu Asn Thr Val His Lys Trp Ile Ser Ile Thr Glu
275 280 285Ala Leu Ala Phe Phe His Cys Cys Leu Asn Pro Ile Leu Tyr Ala Phe
290 295 300Leu Gly Ala Lys Phe Lys Thr Ser Ala Gln His Ala Leu Thr Ser Val305 310 315 320Ser Arg Gly Ser Ser Leu Lys Ile Leu Ser Lys Gly Lys Arg Gly Gly
325 330 335His Ser Ser Val Ser Thr Glu Ser Glu Ser Ser Ser Phe His Ser Ser
340 345 350<210>486<211>1341<212>DNA<213>智人(Homo sapiens)<400>486atgaggactc tgaacacctc tgccatggac gggactgggc tggtggtgga gagggacttc 60tctgttcgta tcctcactgc ctgtttcctg tcgctgctca tcctgtccac gctcctgggg 120aacacgctgg tctgtgctgc cgttatcagg ttccgacacc tgcggtccaa ggtgaccaac 180ttctttgtca tctccttggc tgtgtcagat ctcttggtgg ccgtcctggt catgccctgg 240aaggcagtgg ctgagattgc tggcttctgg ccctttgggt ccttctgtaa catctgggtg 300gcctttgaca tcatgtgctc cactgcatcc atcctcaacc tctgtgtgat cagcgtggac 360aggtattggg ctatctccag ccctttccgg tatgagagaa agatgacccc caaggcagcc 420ttcatcctga tcagtgtggc atggaccttg tctgtactca tctccttcat cccagtgcag 480ctcagctggc acaaggcaaa acccacaagc ccctctgatg gaaatgccac ttccctggct 540gagaccatag acaactgtga ctccagcctc agcaggacat atgccatctc atcctctgta 600ataagctttt acatccctgt ggccatcatg attgtcacct acaccaggat ctacaggatt 660gctcagaaac aaatacggcg cattgcggcc ttggagaggg cagcagtcca cgccaagaat 720tgccagacca ccacaggtaa tggaaagcct gtcgaatgtt ctcaaccgga aagttctttt 780aagatgtcct tcaaaagaga aactaaagtc aagaagactc tgtcggtgat catgggtgtg 840tttgtgtgct gttggctacc tttcttcatc ttgaactgca ttttgccctt ctgtgggtct 900ggggagacgc agcccttctg cattgattcc aacacctttg acgtgtttgt gtggtttggg 960tgggctaatt catccttgaa ccccatcatt tatgccttta atgctgattt tcggaaggca 1020ttttcaaccc tcttaggatg ctacagactt tgccctgcga cgaataatgc catagagacg 1080gtgagtatca ataacaatgg ggccgcgatg ttttccagcc atcatgagcc acgaggctcc 1140atctccaagg agtgcaatct ggtttacctg atcccacatg ctgtgggctc ctctgaggac 1200ctgaaaaagg aggaggcagc tggcatcgcc agacccttgg agaagctgtc cccagcccta 1260tcggtcatat tggactatga cactgacgtc tctctggaga agatccaacc catgacacaa 1320aacggtcagc acccaacctg a 1341<210>487<211>446<212>PRT<213>智人(Homo sapiens)<400>487Met Arg Thr Leu Asn Thr Ser Ala Met Asp Gly Thr Gly Leu Val Val1 5 10 15Glu Arg Asp Phe Ser Val Arg Ile Leu Thr Ala Cys Phe Leu Ser Leu
20 25 30Leu Ile Leu Ser Thr Leu Leu Gly Asn Thr Leu Val Cys Ala Ala Val
35 40 45Ile Arg Phe Arg His Leu Arg Ser Lys Val Thr Asn Phe Phe Val Ile
50 55 60Ser Leu Ala Val Ser Asp Leu Leu Val Ala Val Leu Val Met Pro Trp65 70 75 80Lys Ala Val Ala Glu Ile Ala Gly Phe Trp Pro Phe Gly Ser Phe Cys
85 90 95Asn Ile Trp Val Ala Phe Asp Ile Met Cys Ser Thr Ala Ser Ile Leu
100 105 110Asn Leu Cys Val Ile Ser Val Asp Arg Tyr Trp Ala Ile Ser Ser Pro
115 120 125Phe Arg Tyr Glu Arg Lys Met Thr Pro Lys Ala Ala Phe Ile Leu Ile
130 135 140Ser Val Ala Trp Thr Leu Ser Val Leu Ile Ser Phe Ile Pro Val Gln145 150 155 160Leu Ser Trp His Lys Ala Lys Pro Thr Ser Pro Ser Asp Gly Asn Ala
165 170 175Thr Ser Leu Ala Glu Thr Ile Asp Asn Cys Asp Ser Ser Leu Ser Arg
180 185 190Thr Tyr Ala Ile Ser Ser Ser Val Ile Ser Phe Tyr Ile Pro Val Ala
195 200 205Ile Met Ile Val Thr Tyr Thr Arg Ile Tyr Arg Ile Ala Gln Lys Gln
210 215 220Ile Arg Arg Ile Ala Ala Leu Glu Arg Ala Ala Val His Ala Lys Asn225 230 235 240Cys Gln Thr Thr Thr Gly Asn Gly Lys Pro Val Glu Cys Ser Gln Pro
245 250 255Glu Ser Ser Phe Lys Met Ser Phe Lys Arg Glu Thr Lys Val Lys Lys
260 265 270Thr Leu Ser Val Ile Met Gly Val Phe Val Cys Cys Trp Leu Pro Phe
275 280 285Phe Ile Leu Asn Cys Ile Leu Pro Phe Cys Gly Ser Gly Glu Thr Gln
290 295 300Pro Phe Cys Ile Asp Ser Asn Thr Phe Asp Val Phe Val Trp Phe Gly305 310 315 320Trp Ala Asn Ser Ser Leu Asn Pro Ile Ile Tyr Ala Phe Asn Ala Asp
325 330 335Phe Arg Lys Ala Phe Ser Thr Leu Leu Gly Cys Tyr Arg Leu Cys Pro
340 345 350Ala Thr Asn Asn Ala Ile Glu Thr Val Ser Ile Asn Asn Asn Gly Ala
355 360 365Ala Met Phe Ser Ser His His Glu Pro Arg Gly Ser Ile Ser Lys Glu
370 375 380Cys Asn Leu Val Tyr Leu Ile Pro His Ala Val Gly Ser Ser Glu Asp385 390 395 400Leu Lys Lys Glu Glu Ala Ala Gly Ile Ala Arg Pro Leu Glu Lys Leu
405 410 415Ser Pro Ala Leu Ser Val Ile Leu Asp Tyr Asp Thr Asp Val Ser Leu
420 425 430Glu Lys Ile Gln Pro Met Thr Gln Asn Gly Gln His Pro Thr
435 440 445<210>488<211>1332<212>DNA<213>智人(Homo sapiens)<400>488atggatccac tgaatctgtc ctggtatgat gatgatctgg agaggcagaa ctggagccgg 60cccttcaacg ggtcagacgg gaaggcggac agaccccact acaactacta tgccacacgg 120ctcaccctgc tcatcgctgt catcgtcttc ggcaacgtgc tggtgtgcat ggctgtgtcc 180cgcgagaagg cgctgcagac caccaccaac tacctgatcg tcagccttgc agtggccgac 240ctcctcgtcg ccacactggt catgccctgg gttgtctacc tggaggtggt aggtgagtgg 300aaattcagca ggattcactg tgacatcttc gtcactctgg acgtcatgat gtgcacggcg 360agcatcctga acttgtgtgc catcagcatc gacaggtaca cagctgtggc catgcccatg 420ctgtacaata cgcgctacag ctccaagcgc cgggtcaccg tcatgatctc catcgtctgg 480gtcctgtcct tcaccatctc ctgcccactc ctcttcggac tcaataacgc agaccagaac 540gagtgcatca ttgccaaccc ggccttcgtg gtctactcct ccatcgtctc cttctacgtg 600cccttcattg tcaccctgct ggtctacatc aagatctaca ttgtcctccg cagacgccgc 660aagcgagtca acaccaaacg cagcagccga gctttcaggg cccacctgag ggctccacta 720aagggcaact gtactcaccc cgaggacatg aaactctgca ccgttatcat gaagtctaat 780gggagtttcc cagtgaacag gcggagagta gaggctgccc ggcgagccca ggagctggag 840atggagatgc tctccagcac cagcccaccc gagaggaccc ggtacagccc catccctccc 900agccaccacc agctgactct ccccgacccg tcccaccatg gtctccacag cactcccgac 960agccccgcca aaccagagaa gaatgggcat gccaaagacc accccaagat tgccaagatc 1020tttgagatcc agaccatgcc caatggcaaa acccggacct ccctcaagac catgagccgt 1080aggaagctct cccagcagaa ggagaagaaa gccaatcaga tgctcgccat tgttctcggc 1140gtgttcatca tctgctggct gcccttcttc atcacacaca tcctgaacat acactgtgac 1200tgcaacatcc cgcctgtcct gtacagcgcc ttcacgtggc tgggctatgt caacagcgcc 1260gtgaacccca tcatctacac caccttcaac attgagttcc gcaaggcctt cctgaagatc 1320ctccactgct ga 1332<210>489<211>443<212>PRT<213>智人(Homo sapiens)<400>489Met Asp Pro Leu Asn Leu Ser Trp Tyr Asp Asp Asp Leu Glu Arg Gln1 5 10 15Asn Trp Ser Arg Pro Phe Asn Gly Ser Asp Gly Lys Ala Asp Arg Pro
20 25 30His Tyr Asn Tyr Tyr Ala Thr Arg Leu Thr Leu Leu Ile Ala Val Ile
35 40 45Val Phe Gly Asn Val Leu Val Cys Met Ala Val Ser Arg Glu Lys Ala
50 55 60Leu Gln Thr Thr Thr Asn Tyr Leu Ile Val Ser Leu Ala Val Ala Asp65 70 75 80Leu Leu Val Ala Thr Leu Val Met Pro Trp Val Val Tyr Leu Glu Val
85 90 95Val Gly Glu Trp Lys Phe Ser Arg Ile His Cys Asp Ile Phe Val Thr
100 105 110Leu Asp Val Met Met Cys Thr Ala Ser Ile Leu Asn Leu Cys Ala Ile
115 120 125Ser Ile Asp Arg Tyr Thr Ala Val Ala Met Pro Met Leu Tyr Asn Thr
130 135 140Arg Tyr Ser Ser Lys Arg Arg Val Thr Val Met Ile Ser Ile Val Trp145 150 155 160Val Leu Ser Phe Thr Ile Ser Cys Pro Leu Leu Phe Gly Leu Asn Asn
165 170 175Ala Asp Gln Asn Glu Cys Ile Ile Ala Asn Pro Ala Phe Val Val Tyr
180 185 190Ser Ser Ile Val Ser Phe Tyr Val Pro Phe Ile Val Thr Leu Leu Val
195 200 205Tyr Ile Lys Ile Tyr Ile Val Leu Arg Arg Arg Arg Lys Arg Val Asn
210 215 220Thr Lys Arg Ser Ser Arg Ala Phe Arg Ala His Leu Arg Ala Pro Leu225 230 235 240Lys Gly Asn Cys Thr His Pro Glu Asp Met Lys Leu Cys Thr Val Ile
245 250 255Met Lys Ser Asn Gly Ser Phe Pro Val Asn Arg Arg Arg Val Glu Ala
260 265 270Ala Arg Arg Ala Gln Glu Leu Glu Met Glu Met Leu Ser Ser Thr Ser
275 280 285Pro Pro Glu Arg Thr Arg Tyr Ser Pro Ile Pro Pro Ser His His Gln
290 295 300Leu Thr Leu Pro Asp Pro Ser His His Gly Leu His Ser Thr Pro Asp305 310 315 320Ser Pro Ala Lys Pro Glu Lys Asn Gly His Ala Lys Asp His Pro Lys
325 330 335Ile Ala Lys Ile Phe Glu Ile Gln Thr Met Pro Asn Gly Lys Thr Arg
340 345 350Thr Ser Leu Lys Thr Met Ser Arg Arg Lys Leu Ser Gln Gln Lys Glu
355 360 365Lys Lys Ala Lys Gln Met Leu Ala Ile Val Leu Gly Val Phe Ile Ile
370 375 380Cys Trp Leu Pro Phe Phe Ile Thr His Ile Leu Asn Ile His Cys Asp385 390 395 400Cys Asn Ile Pro Pro Val Leu Tyr Ser Ala Phe Thr Trp Leu Gly Tyr
405 410 415Val Asn Ser Ala Val Asn Pro Ile Ile Tyr Thr Thr Phe Asn Ile Glu
420 425 430Phe Arg Lys Ala Phe Leu Lys Ile Leu His Cys
435 440<210>490<211>1203<212>DNA<213>智人(Homo sapiens)<400>490atggcatctc tgagtcagct gagtagccac ctgaactaca cctgtggggc agagaactcc 60acaggtgcca gccaggcccg cccacatgcc tactatgccc tctcctactg cgcgctcatc 120ctggccatcg tcttcggcaa tggcctggtg tgcatggctg tgctgaagga gcgggccctg 180cagactacca ccaactactt agtagtgagc ctggctgtgg cagacttgct ggtggccacc 240ttggtgatgc cctgggtggt atacctggag gtgacaggtg gagtctggaa tttcagccgc 300atttgctgtg atgtttttgt caccctggat gtcatgatgt gtacagccag catccttaat 360ctctgtgcca tcagcataga caggtacact gcagtggtca tgcccgttca ctaccagcat 420ggcacgggac agagctcctg tcggcgcgtg gccctcatga tcacggccgt ctgggtactg 480gcctttgctg tgtcctgccc tcttctgttt ggctttaata ccacagggga ccccactgtc 540tgctccatct ccaaccctga ttttgtcatc tactcttcag tggtgtcctt ctacctgccc 600tttggagtga ctgtccttgt ctatgccaga atctatgtgg tgctgaaaca aaggagacgg 660aaaaggatcc tcactcgaca gaacagtcag tgcaacagtg tcaggcctgg cttcccccaa 720caaaccctct ctcctgaccc ggcacatctg gagctgaagc gttactacag catctgccag 780gacactgcct tgggtggacc aggcttccaa gaaagaggag gagagttgaa aagagaggag 840aagactcgga attccctgag tcccaccata gcgcccaagc tcagcttaga agttcgaaaa 900ctcagcaatg gcagattatc gacatctttg aagctggggc ccctgcaacc tcggggagtg 960ccacttcggg agaagaaggc aaaacaaatg gtggccattg tgcttggggc cttcattgtc 1020tgctggctgc ccttcttctt gacccatgtt ctcaataccc actgccagac atgccacgtg 1080tccccagagc tttacagtgc cacgacatgg ctgggctacg tgaatagcgc cctcaaccct 1140gtgatctata ccaccttcaa tatcgagttc cggaaagcct tcctcaagat cctgtcttgc 1200tga 1203<210>491<211>400<212>PRT<213>智人(Homo sapiens)<400>491Met Ala Ser Leu Ser Gln Leu Ser Ser His Leu Asn Tyr Thr Cys Gly1 5 10 15Ala Glu Asn Ser Thr Gly Ala Ser Gln Ala Arg Pro His Ala Tyr Tyr
20 25 30Ala Leu Ser Tyr Cys Ala Leu Ile Leu Ala Ile Val Phe Gly Asn Gly
35 40 45Leu Val Cys Met Ala Val Leu Lys Glu Arg Ala Leu Gln Thr Thr Thr
50 55 60Asn Tyr Leu Val Val Ser Leu Ala Val Ala Asp Leu Leu Val Ala Thr65 70 75 80Leu Val Met Pro Trp Val Val Tyr Leu Glu Val Thr Gly Gly Val Trp
85 90 95Asn Phe Ser Arg Ile Cys Cys Asp Val Phe Val Thr Leu Asp Val Met
100 105 110Met Cys Thr Ala Ser Ile Leu Asn Leu Cys Ala Ile Ser Ile Asp Arg
115 120 125Tyr Thr Ala Val Val Met Pro Val His Tyr Gln His Gly Thr Gly Gln
130 135 140Ser Ser Cys Arg Arg Val Ala Leu Met Ile Thr Ala Val Trp Val Leu145 150 155 160Ala Phe Ala Val Ser Cys Pro Leu Leu Phe Gly Phe Asn Thr Thr Gly
165 170 175Asp Pro Thr Val Cys Ser Ile Ser Asn Pro Asp Phe Val Ile Tyr Ser
180 185 190Ser Val Val Ser Phe Tyr Leu Pro Phe Gly Val Thr Val Leu Val Tyr
195 200 205Ala Arg Ile Tyr Val Val Leu Lys Gln Arg Arg Arg Lys Arg Ile Leu
210 215 220Thr Arg Gln Asn Ser Gln Cys Asn Ser Val Arg Pro Gly Phe Pro Gln225 230 235 240Gln Thr Leu Ser Pro Asp Pro Ala His Leu Glu Leu Lys Arg Tyr Tyr
245 250 255Ser Ile Cys Gln Asp Thr Ala Leu Gly Gly Pro Gly Phe Gln Glu Arg
260 265 270Gly Gly Glu Leu Lys Arg Glu Glu Lys Thr Arg Asn Ser Leu Ser Pro
275 280 285Thr Ile Ala Pro Lys Leu Ser Leu Glu Val Arg Lys Leu Ser Asn Gly
290 295 300Arg Leu Ser Thr Ser Leu Lys Leu Gly Pro Leu Gln Pro Arg Gly Val305 310 315 320Pro Leu Arg Glu Lys Lys Ala Lys Gln Met Val Ala Ile Val Leu Gly
325 330 335Ala Phe Ile Val Cys Trp Leu Pro Phe Phe Leu Thr His Val Leu Asn
340 345 350Thr His Cys Gln Thr Cys His Val Ser Pro Glu Leu Tyr Ser Ala Thr
355 360 365Thr Trp Leu Gly Tyr Val Asn Ser Ala Leu Asn Pro Val Ile Tyr Thr
370 375 380Thr Phe Asn Ile Glu Phe Arg Lys Ala Phe Leu Lys Ile Leu Ser Cys385 390 395 400<210>492<211>1434<212>DNA<213>智人(Homo sapiens)<400>492atgctgcegc caggcagcaa cggcaccgcg tacccggggc agttcgctct ataccagcag 60ctggcgcagg ggaacgccgt ggggggctcg gcgggggcac cgccactggg gccctcacag 120gtggtcaccg cctgcctgct gaccctactc atcatctgga ccctgctggg caacgtgctg 180gtgtgcgcag ccatcgtgcg gagccgccac ctgcgcgcca acatgaccaa cgtcttcatc 240gtgtctctgg ccgtgtctga ccttttcgtg gcgctgctgg tcatgccctg gaaggcagtc 300gccgaggtgg ccggttactg gccctttgga gcgttctgcg acgtctgggt ggccttcgac 360atcatgtgct ccactgcctc catcctgaac ctgtgcgtca tcagcgtgga ccgctactgg 420gccatctcca ggcccttccg ctacaagcgc aagatgactc agcgcatggc cttggtcatg 480gtcggcctgg catggacctt gtccatcctc atctccttca ttccggtcca gctcaactgg 540cacagggacc aggcggcctc ttggggcggg ctggacctgc caaacaacct ggccaactgg 600acgccctggg aggaggactt ttgggagccc gacgtgaatg cagagaactg tgactccagc 660ctgaatcgaa cctacgccat ctcttcctcg ctcatcagct tctacatccc cgttgccatc 720atgatcgtga cctacacgcg catctaccgc atcgcccagg tgcagatccg caggatttcc 780tccctggaga gggccgcaga gcacgcgcag agctgccgga gcagcgcagc ctgcgcgccc 840gacaccagcc tgcgcgcttc catcaagaag gagaccaagg ttaaaaagac cctgtcggtg 900atcatggggg tcttcgtgtg ttgctggctg cccttcttca tccttaactg catggtccct 960ttctgcagtg gacaccctga aggccctccg gccggcttcc cctgcgtcag tgagaccacc 1020ttcgacgtct tcgtctggtt cggctgggct aactcctcac tcaaccccgt catctatgcc 1080ttcaacgccg actttcagaa ggtgtttgcc cagctgctgg ggtgcagcca cttctgctcc 1140cgcacgccgg tggagacggt gaacatcagc aatgagctca tctcctacaa ccaagacatc 1200gtcttccaca aggaaatcgc agctgcctac atccacatga tgcccaacgc cgttaccccc 1260ggcaaccggg aggtggacaa cgacgaggag gagggtcctt tcgatcgcat gttccagatc 1320tatcagacgt ccccagatgg tgaccctgtt gctgagtctg tctgggagct ggactgcgag 1380ggggagattt ctttagacaa aataacacct ttcaccccga atggattcca ttaa 1434<210>493<211>477<212>PRT<213>智人(Homo sapiens)<400>493Met Leu Pro Pro Gly Ser Asn Gly Thr Ala Tyr Pro Gly Gln Phe Ala1 5 10 15Leu Tyr Gln Gln Leu Ala Gln Gly Asn Ala Val Gly Gly Ser Ala Gly
20 25 30Ala Pro Pro Leu Gly Pro Ser Gln Val Val Thr Ala Cys Leu Leu Thr
35 40 45Leu Leu Ile Ile Trp Thr Leu Leu Gly Asn Val Leu Val Cys Ala Ala
50 55 60Ile Val Arg Ser Arg His Leu Arg Ala Asn Met Thr Asn Val Phe Ile65 70 75 80Val Ser Leu Ala Val Ser Asp Leu Phe Val Ala Leu Leu Val Met Pro
85 90 95Trp Lys Ala Val Ala Glu Val Ala Gly Tyr Trp Pro Phe Gly Ala Phe
100 105 110Cys Asp Val Trp Val Ala Phe Asp Ile Met Cys Ser Thr Ala Ser Ile
115 120 125Leu Asn Leu Cys Val Ile Ser Val Asp Arg Tyr Trp Ala Ile Ser Arg
130 135 140Pro Phe Arg Tyr Lys Arg Lys Met Thr Gln Arg Met Ala Leu Val Met145 150 155 160Val Gly Leu Ala Trp Thr Leu Ser Ile Leu Ile Ser Phe Ile Pro Val
165 170 175Gln Leu Asn Trp His Arg Asp Gln Ala Ala Ser Trp Gly Gly Leu Asp
180 185 190Leu Pro Asn Asn Leu Ala Asn Trp Thr Pro Trp Glu Glu Asp Phe Trp
195 200 205Glu Pro Asp Val Asn Ala Glu Asn Cys Asp Ser Ser Leu Asn Arg Thr
210 215 220Tyr Ala Ile Ser Ser Ser Leu Ile Ser Phe Tyr Ile Pro Val Ala Ile225 230 235 240Met Ile Val Thr Tyr Thr Arg Ile Tyr Arg Ile Ala Gln Val Gln Ile
245 250 255Arg Arg Ile Ser Ser Leu Glu Arg Ala Ala Glu His Ala Gln Ser Cys
260 265 270Arg Ser Ser Ala Ala Cys Ala Pro Asp Thr Ser Leu Arg Ala Ser Ile
275 280 285Lys Lys Glu Thr Lys Val Lys Lys Thr Leu Ser Val Ile Met Gly Val
290 295 300Phe Val Cys Cys Trp Leu Pro Phe Phe Ile Leu Asn Cys Met Val Pro305 310 315 320Phe Cys Ser Gly His Pro Glu Gly Pro Pro Ala Gly Phe Pro Cys Val
325 330 335Ser Glu Thr Thr Phe Asp Val Phe Val Trp Phe Gly Trp Ala Asn Ser
340 345 350Ser Leu Asn Pro Val Ile Tyr Ala Phe Asn Ala Asp Phe Gln Lys Val
355 360 365Phe Ala Gln Leu Leu Gly Cys Ser His Phe Cys Ser Arg Thr Pro Val
370 375 380Glu Thr Val Asn Ile Ser Asn Glu Leu Ile Ser Tyr Asn Gln Asp Ile385 390 395 400Val Phe His Lys Glu Ile Ala Ala Ala Tyr Ile His Met Met Pro Asn
405 410 415Ala Val Thr Pro Gly Asn Arg Glu Val Asp Asn Asp Glu Glu Glu Gly
420 425 430Pro Phe Asp Arg Met Phe Gln Ile Tyr Gln Thr Ser Pro Asp Gly Asp
435 440 445Pro Val Ala Glu Ser Val Trp Glu Leu Asp Cys Glu Gly Glu Ile Ser
450 455 460Leu Asp Lys Ile Thr Pro Phe Thr Pro Asn Gly Phe His465 470 475<210>494<211>1284<212>DNA<213>智人(Homo sapiens)<400>494atggaaaccc tttgcctcag ggcatccttt tggctggcac tggttggatg tgtaatcagt 60gataatcctg agagatacag cacaaatcta agcaatcatg tggatgattt caccactttt 120cgtggcacag agctcagctt cctggttacc actcatcaac ccactaattt ggtcctaccc 180agcaatggct caatgcacaa ctattgccca cagcagacta aaattacttc agctttcaaa 240tacattaaca ctgtgatatc ttgtactatt ttcatcgtgg gaatggtggg gaatgcaact 300ctgctcagga tcatttacca gaacaaatgt atgaggaatg gccccaacgc gctgatagcc 360agtcttgccc ttggagacct tatctatgtg gtcattgatc tccctatcaa tgtatttaag 420ctgctggctg ggcgctggcc ttttgatcac aatgactttg gcgtatttct ttgcaagctg 480ttcccctttt tgcagaagtc ctcggtgggg atcaccgtcc tcaacctctg cgctcttagt 540gttgacaggt acagagcagt tgcctcctgg agtcgtgttc agggaattgg gattcctttg 600gtaactgcca ttgaaattgt ctccatctgg atcctgtcct ttatcctggc cattcctgaa 660gcgattggct tcgtcatggt accctttgaa tataggggtg aacagcataa aacctgtatg 720ctcaatgcca catcaaaatt catggagttc taccaagatg taaaggactg gtggctcttc 780gggttctatt tctgtatgcc cttggtgtgc actgcgatct tctacaccct catgacttgt 840gagatgttga acagaaggaa tggcagcttg agaattgccc tcagtgaaca tcttaagcag 900cgtcgagaag tgaaaaaaac agttttctgc ttggttgtaa tttttgctct ttgctggttc 960cctcttcact taagccgtat attgaagaaa actgtgtata acgaaatgga caagaaccga 1020tgtgaattac ttagtttctt actgctcatg gattacatcg gtattaactt ggcaaccatg 1080aattcatgta taaaccccat agctctgtat tttgtgagca agaaatttaa aaattgtttc 1140cagtcatgcc tctgctgctg ctgttaccag tccaaaagtc tgatgacctc ggtccccatg 1200aaeggaacaa gcatceagtg gaagaaccac gateaaaaca accacaacac agaccggagc 1260agccataagg acagcatgaa ctga 1284<210>495<211>427<212>PRT<213>智人(Homo sapiens)<400>495Met Glu Thr Leu Cys Leu Arg Ala Ser Phe Trp Leu Ala Leu Val Gly1 5 10 15Cys Val Ile Ser Asp Asn Pro Glu Arg Tyr Ser Thr Asn Leu Ser Asn
20 25 30His Val Asp Asp Phe Thr Thr Phe Arg Gly Thr Glu Leu Ser Phe Leu
35 40 45Val Thr Thr His Gln Pro Thr Asn Leu Val Leu Pro Ser Asn Gly Ser
50 55 60Met His Asn Tyr Cys Pro Gln Gln Thr Lys Ile Thr Ser Ala Phe Lys65 70 75 80Tyr Ile Asn Thr Val Ile Ser Cys Thr Ile Phe Ile Val Gly Met Val
85 90 95Gly Asn Ala Thr Leu Leu Arg Ile Ile Tyr Gln Asn Lys Cys Met Arg
100 105 110Asn Gly Pro Asn Ala Leu Ile Ala Ser Leu Ala Leu Gly Asp Leu Ile
115 120 125Tyr Val Val Ile Asp Leu Pro Ile Asn Val Phe Lys Leu Leu Ala Gly
130 135 140Arg Trp Pro Phe Asp His Asn Asp Phe Gly Val Phe Leu Cys Lys Leu145 150 155 160Phe Pro Phe Leu Gln Lys Ser Ser Val Gly Ile Thr Val Leu Asn Leu
165 170 175Cys Ala Leu Ser Val Asp Arg Tyr Arg Ala Val Ala Ser Trp Ser Arg
180 185 190Val Gln Gly Ile Gly Ile Pro Leu Val Thr Ala Ile Glu Ile Val Ser
195 200 205Ile Trp Ile Leu Ser Phe Ile Leu Ala Ile Pro Glu Ala Ile Gly Phe
210 215 220Val Met Val Pro Phe Glu Tyr Arg Gly Glu Gln His Lys Thr Cys Met225 230 235 240Leu Asn Ala Thr Ser Lys Phe Met Glu Phe Tyr Gln Asp Val Lys Asp
245 250 255Trp Trp Leu Phe Gly Phe Tyr Phe Cys Met Pro Leu Val Cys Thr Ala
260 265 270Ile Phe Tyr Thr Leu Met Thr Cys Glu Met Leu Asn Arg Arg Asn Gly
275 280 285Ser Leu Arg Ile Ala Leu Ser Glu His Leu Lys Gln Arg Arg Glu Val
290 295 300Lys Lys Thr Val Phe Cys Leu Val Val Ile Phe Ala Leu Cys Trp Phe305 310 315 320Pro Leu His Leu Ser Arg Ile Leu Lys Lys Thr Val Tyr Asn Glu Met
325 330 335Asp Lys Asn Arg Cys Glu Leu Leu Ser Phe Leu Leu Leu Met Asp Tyr
340 345 350Ile Gly Ile Asn Leu Ala Thr Met Asn Ser Cys Ile Asn Pro Ile Ala
355 360 365Leu Tyr Phe Val Ser Lys Lys Phe Lys Asn Cys Phe Gln Ser Cys Leu
370 375 380Cys Cys Cys Cys Tyr Gln Ser Lys Ser Leu Met Thr Ser Val Pro Met385 390 395 400Asn Gly Thr Ser Ile Gln Trp Lys Asn His Asp Gln Asn Asn His Asn
405 410 415Thr Asp Arg Ser Ser His Lys Asp Ser Met Asn
420 425<210>496<211>1329<212>DNA<213>智人(Homo sapiens)<400>496atgcagccgc ctccaagtct gtgcggacgc gccctggttg cgctggttct tgcctgcggc 60ctgtcgcgga tctggggaga ggagagaggc ttcccgcccg acagggccac tccgcttttg 120caaaccgcag agataatgac gccacccact aagaccttat ggcccaaggg ttccaacgcc 180agtctggcgc ggtcgttggc acctgcggag gtgcctaaag gagacaggac ggcaggatct 240ccgccacgca ccatctcccc tcccccgtgc caaggaccca tcgagatcaa ggagactttc 300aaatacatca acacggttgt gtcctgcctt gtgttcgtgc tggggatcat cgggaactcc 360acacttctga gaattatcta caagaacaag tgcatgcgaa acggtcccaa tatcttgatc 420gccagcttgg ctctgggaga cctgctgcac atcgtcattg acatccctat caatgtctac 480aagctgctgg cagaggactg gccatttgga gctgagatgt gtaagctggt gcctttcata 540cagaaagcct ccgtgggaat cactgtgctg agtctatgtg ctctgagtat tgacagatat 600cgagctgttg cttcttggag tagaattaaa ggaattgggg ttccaaaatg gacagcagta 660gaaattgttt tgatttgggt ggtctctgtg gttctggctg tccctgaagc cataggtttt 720gatataatta cgatggacta caaaggaagt tatctgcgaa tctgcttgct tcatcccgtt 780cagaagacag ctttcatgca gttttacaag acagcaaaag attggtggct gttcagtttc 840tatttctgct tgccattggc catcactgca tttttttata cactaatgac ctgtgaaatg 900ttgagaaaga aaagtggcat gcagattgct ttaaatgatc acctaaagca gagacgggaa 960gtgaagaaaa ccgtcttttg cctggtcctt gtctttgccc tctgctggct tccccttcac 1020ctcagcagga ttctgaagct cactctttat aatcagaatg atcccaatag atgtgaactt 1080ttgagctttc tgttggtatt ggactatatt ggtatcaaca tggcttcact gaattcctgc 1140attaacccaa ttgctctgta tttggtgagc aaaagattca aaaactgctt taagtcatgc 1200ttatgctgct ggtgccagtc atttgaagaa aaacagtcct tggaggaaaa gcagtcgtgc 1260ttaaagttca aagctaatga tcacggatat gacaacttcc gttccagtaa taaatacagc 1320tcatcttga 1329<210>497<211>442<212>PRT<213>智人(Homo sapiens)<400>497Met Gln Pro Pro Pro Ser Leu Cys Gly Arg Ala Leu Val Ala Leu Val1 5 10 15Leu Ala Cys Gly Leu Ser Arg Ile Trp Gly Glu Glu Arg Gly Phe Pro
20 25 30Pro Asp Arg Ala Thr Pro Leu Leu Gln Thr Ala Glu Ile Met Thr Pro
35 40 45Pro Thr Lys Thr Leu Trp Pro Lys Gly Ser Asn Ala Ser Leu Ala Arg
50 55 60Ser Leu Ala Pro Ala Glu Val Pro Lys Gly Asp Arg Thr Ala Gly Ser65 70 75 80Pro Pro Arg Thr Ile Ser Pro Pro Pro Cys Gln Gly Pro Ile Glu Ile
85 90 95Lys Glu Thr Phe Lys Tyr Ile Asn Thr Val Val Ser Cys Leu Val Phe
100 105 110Val Leu Gly Ile Ile Gly Asn Ser Thr Leu Leu Arg Ile Ile Tyr Lys
115 120 125Asn Lys Cys Met Arg Asn Gly Pro Asn Ile Leu Ile Ala Ser Leu Ala
130 135 140Leu Gly Asp Leu Leu His Ile Val Ile Asp Ile Pro Ile Asn Val Tyr145 150 155 160Lys Leu Leu Ala Glu Asp Trp Pro Phe Gly Ala Glu Met Cys Lys Leu
165 170 175Val Pro Phe Ile Gln Lys Ala Ser Val Gly Ile Thr Val Leu Ser Leu
180 185 190Cys Ala Leu Ser Ile Asp Arg Tyr Arg Ala Val Ala Ser Trp Ser Arg
195 200 205Ile Lys Gly Ile Gly Val Pro Lys Trp Thr Ala Val Glu Ile Val Leu
210 215 220Ile Trp Val Val Ser Val Val Leu Ala Val Pro Glu Ala Ile Gly Phe225 230 235 240Asp Ile Ile Thr Met Asp Tyr Lys Gly Ser Tyr Leu Arg Ile Cys Leu
245 250 255Leu His Pro Val Gln Lys Thr Ala Phe Met Gln Phe Tyr Lys Thr Ala
260 265 270Lys Asp Trp Trp Leu Phe Ser Phe Tyr Phe Cys Leu Pro Leu Ala Ile
275 280 285Thr Ala Phe Phe Tyr Thr Leu Met Thr Cys Glu Met Leu Arg Lys Lys
290 295 300Ser Gly Met Gln Ile Ala Leu Asn Asp His Leu Lys Gln Arg Arg Glu305 310 315 320Val Lys Lys Thr Val Phe Cys Leu Val Leu Val Phe Ala Leu Cys Trp
325 330 335Leu Pro Leu His Leu Ser Arg Ile Leu Lys Leu Thr Leu Tyr Asn Gln
340 345 350Asn Asp Pro Asn Arg Cys Glu Leu Leu Ser Phe Leu Leu Val Leu Asp
355 360 365Tyr Ile Gly Ile Asn Met Ala Ser Leu Asn Ser Cys Ile Asn Pro Ile
370 375 380Ala Leu Tyr Leu Val Ser Lys Arg Phe Lys Asn Cys Phe Lys Ser Cys385 390 395 400Leu Cys Cys Trp Cys Gln Ser Phe Glu Glu Lys Gln Ser Leu Glu Glu
405 410 415Lys Gln Ser Cys Leu Lys Phe Lys Ala Asn Asp His Gly Tyr Asp Asn
420 425 430Phe Arg Ser Ser Asn Lys Tyr Ser Ser Ser
435 440<210>498<211>1053<212>DNA<213>智人(Homo sapiens)<400>498atggagacaa attcctctct ccccacgaac atctctggag ggacacctgc tgtatctgct 60ggctatctct tcctggatat catcacttat ctggtatttg cagtcacctt tgtcctcggg 120gtcctgggca acgggcttgt gatctgggtg gctggattcc ggatgacaca cacagtcacc 180accatcagtt acctgaacct ggccgtggct gacttctgtt tcacctccac tttgccattc 240ttcatggtca ggaaggccat gggaggacat tggcctttcg gctggttcct gtgcaaattc 300gtctttacca tagtggacat caacttgttc ggaagtgtct tcctgatcgc cctcattgct 360ctggaccgct gtgtttgcgt cctgcatcca gtctggaccc agaaccaccg caccgtgagc 420ctggccaaga aggtgatcat tgggccctgg gtgatggctc tgctcctcac attgccagtt 480atcattcgtg tgactacagt acctggtaaa acggggacag tagcctgcac ttttaacttt 540tcgccctgga ccaacgaccc taaagagagg ataaatgtgg ccgttgccat gttgacggtg 600agaggcatca tccggttcat cattggcttc agcgcaccca tgtccatcgt tgctgtcagt 660tatgggctta ttgccaccaa gatccacaag caaggcttga ttaagtccag tcgtcccaaa 720cgggtcctct cctttgtcgc agcagccttt tttctctgct ggtccccata tcaggtggtg 780gcccttatag ccacagtcag aatccgtgag ttattgcaag gcatgtacaa agaaattggt 840attgcagtgg atgtgacaag tgccctggcc ttcttcaaca gctgcctcaa ccccatgctc 900tatgtcttca tgggccagga cttccgggag aggctgatcc acgcccttcc cgccagtctg 960gagagggccc tgaccgagga ctcaacccaa accagtgaca cagctaccaa ttctacttta 1020ccttctgcag aggtggagtt acaggcaaag tga 1053<210>499<211>350<212>PRT<213>智人(Homo sapiens)<400>499Met Glu Thr Asn Ser Ser Leu Pro Thr Asn Ile Ser Gly Gly Thr Pro1 5 10 15Ala Val Ser Ala Gly Tyr Leu Phe Leu Asp Ile Ile Thr Tyr Leu Val
20 25 30Phe Ala Val Thr Phe Val Leu Gly Val Leu Gly Asn Gly Leu Val Ile
35 40 45Trp Val Ala Gly Phe Arg Met Thr His Thr Val Thr Thr Ile Ser Tyr
50 55 60Leu Asn Leu Ala Val Ala Asp Phe Cys Phe Thr Ser Thr Leu Pro Phe65 70 75 80Phe Met Val Arg Lys Ala Met Gly Gly His Trp Pro Phe Gly Trp Phe
85 90 95Leu Cys Lys Phe Val Phe Thr Ile Val Asp Ile Asn Leu Phe Gly Ser
100 105 110Val Phe Leu Ile Ala Leu Ile Ala Leu Asp Arg Cys Val Cys Val Leu
115 120 125His Pro Val Trp Thr Gln Asn His Arg Thr Val Ser Leu Ala Lys Lys
130 135 140Val Ile Ile Gly Pro Trp Val Met Ala Leu Leu Leu Thr Leu Pro Val145 150 155 160Ile Ile Arg Val Thr Thr Val Pro Gly Lys Thr Gly Thr Val Ala Cys
165 170 175Thr Phe Asn Phe Ser Pro Trp Thr Asn Asp Pro Lys Glu Arg Ile Asn
180 185 190Val Ala Val Ala Met Leu Thr Val Arg Gly Ile Ile Arg Phe Ile Ile
195 200 205Gly Phe Ser Ala Pro Met Ser Ile Val Ala Val Ser Tyr Gly Leu Ile
210 215 220Ala Thr Lys Ile His Lys Gln Gly Leu Ile Lys Ser Ser Arg Pro Lys225 230 235 240Arg Val Leu Ser Phe Val Ala Ala Ala Phe Phe Leu Cys Trp Ser Pro
245 250 255Tyr Gln Val Val Ala Leu Ile Ala Thr Val Arg Ile Arg Glu Leu Leu
260 265 270Gln Gly Met Tyr Lys Glu Ile Gly Ile Ala Val Asp Val Thr Ser Ala
275 280 285Leu Ala Phe Phe Asn Ser Cys Leu Asn Pro Met Leu Tyr Val Phe Met
290 295 300Gly Gln Asp Phe Arg Glu Arg Leu Ile His Ala Leu Pro Ala Ser Leu305 310 315 320Glu Arg Ala Leu Thr Glu Asp Ser Thr Gln Thr Ser Asp Thr Ala Thr
325 330 335Asn Ser Thr Leu Pro Ser Ala Glu Val Glu Leu Gln Ala Lys
340 345 350<210>500<211>1056<212>DNA<213>智人(Homo sapiens)<400>500atggaaacca acttctccac tcctctgaat gaatatgaag aagtgtccta tgagtctgct 60ggctacactg ttctgcggat cctcccattg gtggtgcttg gggtcacctt tgtcctcggg 120gtcctgggca atgggcttgt gatctgggtg gctggattcc ggatgacacg cacagtcacc 180accatctgtt acctgaacct ggccctggct gacttttctt tcacggccac attaccattc 240ctcattgtct ccatggccat gggagaaaaa tggccttttg gctggttcct gtgtaagtta 300attcacatcg tggtggacat caacctcttt ggaagtgtct tcttgattgg tttcattgca 360ctggaccgct gcatttgtgt cctgcatcca gtctgggccc agaaccaccg cactgtgagt 420ctggccatga aggtgatcgt cggaccttgg attcttgctc tagtccttac cttgccagtt 480ttcctctttt tgactacagt aactattcca aatggggaca catactgtac tttcaacttt 540gcatcctggg gtggcacccc tgaggagagg ctgaaggtgg ccattaccat gctgacagcc 600agagggatta tccggtttgt cattggcttt agcttgccga tgtccattgt tgccatctgc 660tatgggctca ttgcagccaa gatccacaaa aagggcatga ttaaatccag ccgtcccaaa 720cgggtcctca ctgctgtggt ggcttctttc ttcatctgtt ggtttccctt tcaactggtt 780gcccttctgg gcaccgtctg gctcaaagag atgttgttct atggcaagta caaaatcatt 840gacatcctgg ttaacccaac gagctccctg gccttcttca acagctgcct caaccccatg 900ctttacgtct ttgtgggcca agacttccga gagagactga tccactccct gcccaccagt 960ctggagaggg ccctgtctga ggactcagcc ccaactaatg acacggctgc caattctgct 1020tcacctcctg cagagactga gttacaggca atgtga 1056<210>501<211>351<212>PRT<213>智人(Homo sapiens)<400>501Met Glu Thr Asn Phe Ser Thr Pro Leu Asn Glu Tyr Glu Glu Val Ser1 5 10 15Tyr Glu Ser Ala Gly Tyr Thr Val Leu Arg Ile Leu Pro Leu Val Val
20 25 30Leu Gly Val Thr Phe Val Leu Gly Val Leu Gly Asn Gly Leu Val Ile
35 40 45Trp Val Ala Gly Phe Arg Met Thr Arg Thr Val Thr Thr Ile Cys Tyr
50 55 60Leu Asn Leu Ala Leu Ala Asp Phe Ser Phe Thr Ala Thr Leu Pro Phe65 70 75 80Leu Ile Val Ser Met Ala Met Gly Glu Lys Trp Pro Phe Gly Trp Phe
85 90 95Leu Cys Lys Leu Ile His Ile Val Val Asp Ile Asn Leu Phe Gly Ser
100 105 110Val Phe Leu Ile Gly Phe Ile Ala Leu Asp Arg Cys Ile Cys Val Leu
115 120 125His Pro Val Trp Ala Gln Asn His Arg Thr Val Ser Leu Ala Met Lys
130 135 140Val Ile Val Gly Pro Trp Ile Leu Ala Leu Val Leu Thr Leu Pro Val145 150 155 160Phe Leu Phe Leu Thr Thr Val Thr Ile Pro Asn Gly Asp Thr Tyr Cys
165 170 175Thr Phe Asn Phe Ala Ser Trp Gly Gly Thr Pro Glu Glu Arg Leu Lys
180 185 190Val Ala Ile Thr Met Leu Thr Ala Arg Gly Ile Ile Arg Phe Val Ile
195 200 205Gly Phe Ser Leu Pro Met Ser Ile Val Ala Ile Cys Tyr Gly Leu Ile
210 215 220Ala Ala Lys Ile His Lys Lys Gly Met Ile Lys Ser Ser Arg Pro Lys225 230 235 240Arg Val Leu Thr Ala Val Val Ala Ser Phe Phe Ile Cys Trp Phe Pro
245 250 255Phe Gln Leu Val Ala Leu Leu Gly Thr Val Trp Leu Lys Glu Met Leu
260 265 270Phe Tyr Gly Lys Tyr Lys Ile Ile Asp Ile Leu Val Asn Pro Thr Ser
275 280 285Ser Leu Ala Phe Phe Asn Ser Cys Leu Asn Pro Met Leu Tyr Val Phe
290 295 300Val Gly Gln Asp Phe Arg Glu Arg Leu Ile His Ser Leu Pro Thr Ser305 310 315 320Leu Glu Arg Ala Leu Ser Glu Asp Ser Ala Pro Thr Asn Asp Thr Ala
325 330 335Ala Asn Ser Ala Ser Pro Pro Ala Glu Thr Glu Leu Gln Ala Met
340 345 350<210>502<211>1050<212>DNA<213>智人(Homo sapiens)<400>502atggagctgg cggtcgggaa cctcagcgag ggcaacgcga gctgtccgga gccccccgcc 60ccggagcccg ggccgctgtt cggcatcggc gtggagaact tcgtcacgct ggtggtgttc 120ggcctgatct tcgcgctggg cgtgctgggc aacagcctag tgatcaccgt gctggcgcgc 180agcaagccgg gcaagccgcg gagcaccacc aacctgttca tcctcaacct gagcatcgcc 240gacctggcct acctgctctt ctgcatcccc ttccaggcca ccgtgtacgc gctgcccacc 300tgggtgctgg gcgccttcat ctgcaagttc atccactact tcttcaccgt gtccatgctg 360gtgagcatct tcaccctggc cgcgatgtcc gtggaccgct acgtggccat cgtgcactcg 420cggcgctcct cctccctcag ggtgtcccgc aacgcgctgc tgggcgtggg ctgcatctgg 480gcgctgtcca ttgccatggc ctcgcccgtg gcctaccacc agggcctctt ccacccgcgc 540gccagcaacc agaccttctg ctgggagcag tggcccgacc ctcgccacaa gaaggcctac 600gtggtgtgca ccttcgtctt cggctacctg ctgccgctcc tgctcatctg cttctgctat 660gccaaggtcc ttaatcactt gcataaaaag ttgaagaaca tgtcaaagaa gtctgaagca 720tccaagaaaa agactaaaca gacagttctg gtggtggttg tggtgtttgg aatctcctgg 780ctgccgcacc acatcatcca tctctgggct gagtttggag ttttcccgct gacgccggct 840tccttcctct tcagaatcac cgcccactgc ctggcgtaca gcaattcctc cgtgaatcct 900atcatttatg catttctctc tgaaaatttc aggaaggcct ataaacaagt gttcaagtgt 960cacattcgca aagattcaca cctgagtgat actaaagaaa ataaaagtcg aatagacacc 1020ccaccatcaa ccaattgtac tcatgtgtga 1050<210>503<211>349<212>PRT<213>智人(Homo sapiens)<400>503Met Glu Leu Ala Val Gly Asn Leu Ser Glu Gly Asn Ala Ser Cys Pro1 5 10 15Glu Pro Pro Ala Pro Glu Pro Gly Pro Leu Phe Gly Ile Gly Val Glu
20 25 30Asn Phe Val Thr Leu Val Val Phe Gly Leu Ile Phe Ala Leu Gly Val
35 40 45Leu Gly Asn Ser Leu Val Ile Thr Val Leu Ala Arg Ser Lys Pro Gly
50 55 60Lys Pro Arg Ser Thr Thr Asn Leu Phe Ile Leu Asn Leu Ser Ile Ala65 70 75 80Asp Leu Ala Tyr Leu Leu Phe Cys Ile Pro Phe Gln Ala Thr Val Tyr
85 90 95Ala Leu Pro Thr Trp Val Leu Gly Ala Phe Ile Cys Lys Phe Ile His
100 105 110Tyr Phe Phe Thr Val Ser Met Leu Val Ser Ile Phe Thr Leu Ala Ala
115 120 125Met Ser Val Asp Arg Tyr Val Ala Ile Val His Ser Arg Arg Ser Ser
130 135 140Ser Leu Arg Val Ser Arg Asn Ala Leu Leu Gly Val Gly Cys Ile Trp145 150 155 160Ala Leu Ser Ile Ala Met Ala Ser Pro Val Ala Tyr His Gln Gly Leu
165 170 175Phe His Pro Arg Ala Ser Asn Gln Thr Phe Cys Trp Glu Gln Trp Pro
180 185 190Asp Pro Arg His Lys Lys Ala Tyr Val Val Cys Thr Phe Val Phe Gly
195 200 205Tyr Leu Leu Pro Leu Leu Leu Ile Cys Phe Cys Tyr Ala Lys Val Leu
210 215 220Asn His Leu His Lys Lys Leu Lys Asn Met Ser Lys Lys Ser Glu Ala225 230 235 240Ser Lys Lys Lys Thr Lys Gln Thr Val Leu Val Val Val Val Val Phe
245 250 255Gly Ile Ser Trp Leu Pro His His Ile Ile His Leu Trp Ala Glu Phe
260 265 270Gly Val Phe Pro Leu Thr Pro Ala Ser Phe Leu Phe Arg Ile Thr Ala
275 280 285His Cys Leu Ala Tyr Ser Asn Ser Ser Val Asn Pro Ile Ile Tyr Ala
290 295 300Phe Leu Ser Glu Asn Phe Arg Lys Ala Tyr Lys Gln Val Phe Lys Cys305 310 315 320His Ile Arg Lys Asp Ser His Leu Ser Asp Thr Lys Glu Asn Lys Ser
325 330 335Arg Ile Asp Thr Pro Pro Ser Thr Asn Cys Thr His Val
340 345<210>504<211>1164<212>DNA<213>智人(Homo sapiens)<400>504atgaacgtct cgggctgccc aggggccggg aacgcgagcc aggcgggcgg cgggggaggc 60tggcaccccg aggcggtcat cgtgcccctg ctcttcgcgc tcatcttcct cgtgggcacc 120gtgggcaaca cgctggtgct ggcggtgctg ctgcgcggcg gccaggcggt cagcactacc 180aacctgttca tccttaacct gggcgtggcc gacctgtgtt tcatcctgtg ctgcgtgccc 240ttccaggcca ccatctacac cctggacggc tgggtgttcg gctcgctgct gtgcaaggcg 300gtgcacttcc tcatcttcct caccatgcac gccagcagct tcacgctggc cgccgtctcc 360ctggacaggt atctggccat ccgctacccg ctgcactccc gcgagctgcg cacgcctcga 420aacgcgctgg cagccatcgg gctcatctgg gggctgtcgc tgctcttctc cgggccctac 480ctgagctact accgccagtc gcagctggcc aacctgaccg tgtgccatcc cgcgtggagc 540gcccctcgcc gccgcgccat ggacatctgc accttcgtct tcagctacct gcttcctgtg 600ctggttctcg gcctgaccta cgcgcgcacc ttgcgctacc tctggcgcgc cgtcgacccg 660gtggccgcgg gctcgggtgc ccggcgcgcc aagcgcaagg tgaaacgcat gatcctcatc 720gtggccgcgc tcttctgcct ctgctggatg ccccaccacg cgctcatcct ctgcgtgtgg 780ttcggccagt tcccgctcac gcgcgccact tatgcgcttc gcatcctctc gcacctggtc 840tcctacgcca actcctgcgt caaccccatc gtttacgcgc tggtctccaa gcacttccgc 900aaaggcttcc gcacgatctg cgcgggcctg ctgggccgtg ccccaggccg agcctcgggc 960cgtgtgtgcg ctgccgcgcg gggcacccac agtggcagcg tgttggagcg cgagtccagc 1020gacctgttgc acatgagcga ggcggcgggg gcccttcgtc cctgccccgg cgcttcccag 1080ccatgcatcc tcgagccctg tcctggcccg tcctggcagg gcccaaaggc aggcgacagc 1140atcctgacgg ttgatgtggc ctga 1164<210>505<211>387<212>PRT<213>智人(Homo sapiens)<400>505Met Asn Val Ser Gly Cys Pro Gly Ala Gly Asn Ala Ser Gln Ala Gly1 5 10 15Gly Gly Gly Gly Trp His Pro Glu Ala Val Ile Val Pro Leu Leu Phe
20 25 30Ala Leu Ile Phe Leu Val Gly Thr Val Gly Asn Thr Leu Val Leu Ala
35 40 45Val Leu Leu Arg Gly Gly Gln Ala Val Ser Thr Thr Asn Leu Phe Ile
50 55 60Leu Asn Leu Gly Val Ala Asp Leu Cys Phe Ile Leu Cys Cys Val Pro65 70 75 80Phe Gln Ala Thr Ile Tyr Thr Leu Asp Gly Trp Val Phe Gly Ser Leu
85 90 95Leu Cys Lys Ala Val His Phe Leu Ile Phe Leu Thr Met His Ala Ser
100 105 110Ser Phe Thr Leu Ala Ala Val Ser Leu Asp Arg Tyr Leu Ala Ile Arg
115 120 125Tyr Pro Leu His Ser Arg Glu Leu Arg Thr Pro Arg Asn Ala Leu Ala
130 135 140Ala Ile Gly Leu Ile Trp Gly Leu Ser Leu Leu Phe Ser Gly Pro Tyr145 150 155 160Leu Ser Tyr Tyr Arg Gln Ser Gln Leu Ala Asn Leu Thr Val Cys His
165 170 175Pro Ala Trp Ser Ala Pro Arg Arg Arg Ala Met Asp Ile Cys Thr Phe
180 185 190Val Phe Ser Tyr Leu Leu Pro Val Leu Val Leu Gly Leu Thr Tyr Ala
195 200 205Arg Thr Leu Arg Tyr Leu Trp Arg Ala Val Asp Pro Val Ala Ala Gly
210 215 220Ser Gly Ala Arg Arg Ala Lys Arg Lys Val Lys Arg Met Ile Leu Ile225 230 235 240Val Ala Ala Leu Phe Cys Leu Cys Trp Met Pro His His Ala Leu Ile
245 250 255Leu Cys Val Trp Phe Gly Gln Phe Pro Leu Thr Arg Ala Thr Tyr Ala
260 265 270Leu Arg Ile Leu Ser His Leu Val Ser Tyr Ala Asn Ser Cys Val Asn
275 280 285Pro Ile Val Tyr Ala Leu Val Ser Lys His Phe Arg Lys Gly Phe Arg
290 295 300Thr Ile Cys Ala Gly Leu Leu Gly Arg Ala Pro Gly Arg Ala Ser Gly305 310 315 320Arg Val Cys Ala Ala Ala Arg Gly Thr His Ser Gly Ser Val Leu Glu
325 330 335Arg Glu Ser Ser Asp Leu Leu His Met Ser Glu Ala Ala Gly Ala Leu
340 345 350Arg Pro Cys Pro Gly Ala Ser Gln Pro Cys Ile Leu Glu Pro Cys Pro
355 360 365Gly Pro Ser Trp Gln Gly Pro Lys Ala Gly Asp Ser Ile Leu Thr Val
370 375 380Asp Val Ala385<210>506<211>1401<212>DNA<213>智人(Homo sapiens)<400>506atgactacct ctccgatcct gcagctgctg ctgcggctct cactgtgcgg gctgctgctc 60cagagggcgg agacaggctc taaggggcag acggcggggg agctgtacca gcgctgggaa 120cggtaccgca gggagtgcca ggagaccttg gcagccgcgg aaccgccttc aggcctcgcc 180tgtaacgggt ccttcgatat gtacgtctgc tgggactatg ctgcacccaa tgccactgcc 240cgtgcgtcct gcccctggta cctgccctgg caccaccatg tggctgcagg tttcgtcctc 300cgccagtgtg gcagtgatgg ccaatgggga ctttggagag accatacaca atgtgagaac 360ccagagaaga atgaggcctt tctggaccaa aggctcatct tggagcggtt gcaggtcatg 420tacactgtcg gctactccct gtctctcgcc acactgctgc tagccctgct catcttgagt 480ttgttcaggc ggctacattg cactagaaac tatatccaca tcaacctgtt cacgtctttc 540atgctgcgag ctgcggccat tctcagccga gaccgtctgc tacctcgacc tggcccctac 600cttggggacc aggcccttgc gctgtggaac caggccctcg ctgcctgccg cacggcccag 660atcgtgaccc agtactgcgt gggtgccaac tacacgtggc tgctggtgga gggcgtctac 720ctgcacagtc tcctggtgct cgtgggaggc tccgaggagg gccacttccg ctactacctg 780ctcctcggct ggggggcccc cgcgcttttc gtcattccct gggtgatcgt caggtacctg 840tacgagaaca cgcagtgctg ggagcgcaac gaagtcaagg ccatttggtg gattatacgg 900acccccatcc tcatgaccat cttgattaat ttcctcattt ttatccgcat tcttggcatt 960ctcctgtcca agctgaggac acggcaaatg cgctgccggg attaccggct gaggctggct 1020cgctccccgc tgacgctggt gcccctgctg ggtgtccacg aggtggtgtt tgctcccgtg 1080acagaggaac aggcccgggg cgccctgcgc ttcgccaagc tcggctttga gatcttcctc 1140agctccttcc agggcttcct ggtcagcgtc ctctactgct tcatcaacaa ggaggtgcag 1200tcggagatcc gccgtggctg gcaccactgc cgcctgcgcc gcagcctggg cgaggagcaa 1260cgccagctcc cggagcgcgc cttccgggcc ctgccctccg gctccggccc gggcgaggtc 1320cccaccagcc gcggcttgtc ctcggggacc ctcccagggc ctgggaatga ggccagccgg 1380gagttggaaa gttactgcta g 1401<210>507<211>466<212>PRT<213>智人(Homo sapiens)<400>507Met Thr Thr Ser Pro Ile Leu Gln Leu Leu Leu Arg Leu Ser Leu Cys1 5 10 15Gly Leu Leu Leu Gln Arg Ala Glu Thr Gly Ser Lys Gly Gln Thr Ala
20 25 30Gly Glu Leu Tyr Gln Arg Trp Glu Arg Tyr Arg Arg Glu Cys Gln Glu
35 40 45Thr Leu Ala Ala Ala Glu Pro Pro Ser Gly Leu Ala Cys Asn Gly Ser
50 55 60Phe Asp Met Tyr Val Cys Trp Asp Tyr Ala Ala Pro Asn Ala Thr Ala65 70 75 80Arg Ala Ser Cys Pro Trp Tyr Leu Pro Trp His His His Val Ala Ala
85 90 95Gly Phe Val Leu Arg Gln Cys Gly Ser Asp Gly Gln Trp Gly Leu Trp
100 105 110Arg Asp His Thr Gln Cys Glu Asn Pro Glu Lys Asn Glu Ala Phe Leu
115 120 125Asp Gln Arg Leu Ile Leu Glu Arg Leu Gln Val Met Tyr Thr Val Gly
130 135 140Tyr Ser Leu Ser Leu Ala Thr Leu Leu Leu Ala Leu Leu Ile Leu Ser145 150 155 160Leu Phe Arg Arg Leu His Cys Thr Arg Asn Tyr Ile His Ile Asn Leu
165 170 175Phe Thr Ser Phe Met Leu Arg Ala Ala Ala Ile Leu Ser Arg Asp Arg
180 185 190Leu Leu Pro Arg Pro Gly Pro Tyr Leu Gly Asp Gln Ala Leu Ala Leu
195 200 205Trp Asn Gln Ala Leu Ala Ala Cys Arg Thr Ala Gln Ile Val Thr Gln
210 215 220Tyr Cys Val Gly Ala Asn Tyr Thr Trp Leu Leu Val Glu Gly Val Tyr225 230 235 240Leu His Ser Leu Leu Val Leu Val Gly Gly Ser Glu Glu Gly His Phe
245 250 255Arg Tyr Tyr Leu Leu Leu Gly Trp Gly Ala Pro Ala Leu Phe Val Ile
260 265 270Pro Trp Val Ile Val Arg Tyr Leu Tyr Glu Asn Thr Gln Cys Trp Glu
275 280 285Arg Asn Glu Val Lys Ala Ile Trp Trp Ile Ile Arg Thr Pro Ile Leu
290 295 300Met Thr Ile Leu Ile Asn Phe Leu Ile Phe Ile Arg Ile Leu Gly Ile305 310 315 320Leu Leu Ser Lys Leu Arg Thr Arg Gln Met Arg Cys Arg Asp Tyr Arg
325 330 335Leu Arg Leu Ala Arg Ser Pro Leu Thr Leu Val Pro Leu Leu Gly Val
340 345 350His Glu Val Val Phe Ala Pro Val Thr Glu Glu Gln Ala Arg Gly Ala
355 360 365Leu Arg Phe Ala Lys Leu Gly Phe Glu Ile Phe Leu Ser Ser Phe Gln
370 375 380Gly Phe Leu Val Ser Val Leu Tyr Cys Phe Ile Asn Lys Glu Val Gln385 390 395 400Ser Glu Ile Arg Arg Gly Trp His His Cys Arg Leu Arg Arg Ser Leu
405 410 415Gly Glu Glu Gln Arg Gln Leu Pro Glu Arg Ala Phe Arg Ala Leu Pro
420 425 430Ser Gly Ser Gly Pro Gly Glu Val Pro Thr Ser Arg Gly Leu Ser Ser
435 440 445Gly Thr Leu Pro Gly Pro Gly Asn Glu Ala Ser Arg Glu Leu Glu Ser
450 455 460Tyr Cys465<210>508<211>1002<212>DNA<213>智人(Homo sapiens)<400>508atggagtcct caggcaaccc agagagcacc accttttttt actatgacct tcagagccag 60ccgtgtgaga accaggcctg ggtctttgct accctcgcca ccactgtcct gtactgcctg 120gtgtttctcc tcagcctagt gggcaacagc ctggtcctgt gggtcctggt gaagtatgag 180agcctggagt ccctcaccaa catcttcatc ctcaacctgt gcctctcaga cctggtgttc 240gcctgcttgt tgcctgtgtg gatctcccca taccactggg gctgggtgct gggagacttc 300ctctgcaaac tcctcaatat gatcttctcc atcagcctct acagcagcat cttcttcctg 360accatcatga ccatccaccg ctacctgtcg gtagtgagcc ccctctccac cctgcgcgtc 420cccaccctcc gctgccgggt gctggtgacc atggctgtgt gggtagccag catcctgtcc 480tccatcctcg acaccatctt ccacaaggtg ctttcttcgg gctgtgatta ttccgaactc 540acgtggtacc tcacctccgt ctaccagcac aacctcttct tcctgctgtc cctggggatt 600atcctgttct gctacgtgga gatcctcagg accctgttcc gctcacgctc caagcggcgc 660caccgcacga aaaagctcat cttcgccatc gtggtggcct acttcctcag ctggggtccc 720tacaacttca ccctgtttct gcagacgctg tttcggaccc agatcatccg gagctgcgag 780gccaaacagc agctagaata cgccctgctc atctgccgca acctcgcctt ctcccactgc 840tgctttaacc cggtgctcta tgtcttcgtg ggggtcaagt tccgcacaca cctgaaacat 900gttctccggc agttctggtt ctgccggctg caggcaccca gcccagcctc gatcccccac 960tcccctggtg ccttcgccta tgagggcgcc tccttctact ga 1002<210>509<211>333<212>PRT<213>智人(Homo sapiens)<400>509Met Glu Ser Ser Gly Asn Pro Glu Ser Thr Thr Phe Phe Tyr Tyr Asp1 5 10 15Leu Gln Ser Gln Pro Cys Glu Asn Gln Ala Trp Val Phe Ala Thr Leu
20 25 30Ala Thr Thr Val Leu Tyr Cys Leu Val Phe Leu Leu Ser Leu Val Gly
35 40 45Asn Ser Leu Val Leu Trp Val Leu Val Lys Tyr Glu Ser Leu Glu Ser
50 55 60Leu Thr Asn Ile Phe Ile Leu Asn Leu Cys Leu Ser Asp Leu Val Phe65 70 75 80Ala Cys Leu Leu Pro Val Trp Ile Ser Pro Tyr His Trp Gly Trp Val
85 90 95Leu Gly Asp Phe Leu Cys Lys Leu Leu Asn Met Ile Phe Ser Ile Ser
100 105 110Leu Tyr Ser Ser Ile Phe Phe Leu Thr Ile Met Thr Ile His Arg Tyr
115 120 125Leu Ser Val Val Ser Pro Leu Ser Thr Leu Arg Val Pro Thr Leu Arg
130 135 140Cys Arg Val Leu Val Thr Met Ala Val Trp Val Ala Ser Ile Leu Ser145 150 155 160Ser Ile Leu Asp Thr Ile Phe His Lys Val Leu Ser Ser Gly Cys Asp
165 170 175Tyr Ser Glu Leu Thr Trp Tyr Leu Thr Ser Val Tyr Gln His Asn Leu
180 185 190Phe Phe Leu Leu Ser Leu Gly Ile Ile Leu Phe Cys Tyr Val Glu Ile
195 200 205Leu Arg Thr Leu Phe Arg Ser Arg Ser Lys Arg Arg His Arg Thr Lys
210 215 220Lys Leu Ile Phe Ala Ile Val Val Ala Tyr Phe Leu Ser Trp Gly Pro225 230 235 240Tyr Asn Phe Thr Leu Phe Leu Gln Thr Leu Phe Arg Thr Gln Ile Ile
245 250 255Arg Ser Cys Glu Ala Lys Gln Gln Leu Glu Tyr Ala Leu Leu Ile Cys
260 265 270Arg Asn Leu Ala Phe Ser His Cys Cys Phe Asn Pro Val Leu Tyr Val
275 280 285Phe Val Gly Val Lys Phe Arg Thr His Leu Lys His Val Leu Arg Gln
290 295 300Phe Trp Phe Cys Arg Leu Gln Ala Pro Ser Pro Ala Ser Ile Pro His305 310 315 320Ser Pro Gly Ala Phe Ala Tyr Glu Gly Ala Ser Phe Tyr
325 330<210>510<211>1155<212>DNA<213>智人(Homo sapiens)<400>510atggctctaa atgactgttt ccttctgaac ttggaggtgg accatttcat gcactgcaac 60atctccagtc acagtgcgga tctccccgtg aacgatgact ggtcccaccc ggggatcctc 120tatgtcatcc ctgcagttta tggggttatc attctgatag gcctcattgg caacatcact 180ttgatcaaga tcttctgtac agtcaagtcc atgcgaaacg ttccaaacct gttcatttcc 240agtctggctt tgggagacct gctcctccta ataacgtgtg ctccagtgga tgccagcagg 300tacctggctg acagatggct atttggcagg attggctgca aactgatccc ctttatacag 360cttacctctg ttggggtgtc tgtcttcaca ctcacggcgc tctcggcaga cagatacaaa 420gccattgtcc ggccaatgga tatccaggcc tcccatgccc tgatgaagat ctgcctcaaa 480gccgccttta tctggatcat ctccatgctg ctggccattc cagaggccgt gttttctgac 540ctccatccct tccatgagga aagcaccaac cagaccttca ttagctgtgc cccataccca 600cactctaatg agcttcaccc caaaatccat tctatggctt cctttctggt cttctacgtc 660atcccactgt cgatcatctc tgtttactac tacttcattg ctaaaaatct gatccagagt 720gcttacaatc ttcccgtgga agggaatata catgtcaaga agcagattga atcccggaag 780cgacttaaga agacagtgct ggtgtttgtg ggcctgttcg ccttctgctg gctccccaat 840catgtcatct acctgtaccg ctcctaccac tactctgagg tggacacctc catgctccac 900tttgtcacca gcatctgtgc ccgcctcctg gccttcacca actcctgcgt gaaccccttt 960gccctctacc tgctgagcaa gagtttcagg aaacagttca acactcagct gctctgttgc 1020cagcctggcc tgatcatccg gtctcacagc actggaagga gtacaacctg catgacctcc 1080ctcaagagta ccaacccctc cgtggccacc tttagcctca tcaatggaaa catctgtcac 1140gagcggtatg tctag 1155<210>511<211>384<212>PRT<213>智人(Homo sapiens)<400>511Met Ala Leu Asn Asp Cys Phe Leu Leu Asn Leu Glu Val Asp His Phe1 5 10 15Met His Cys Asn Ile Ser Ser His Ser Ala Asp Leu Pro Val Asn Asp
20 25 30Asp Trp Ser His Pro Gly Ile Leu Tyr Val Ile Pro Ala Val Tyr Gly
35 40 45Val Ile Ile Leu Ile Gly Leu Ile Gly Asn Ile Thr Leu Ile Lys Ile
50 55 60Phe Cys Thr Val Lys Ser Met Arg Asn Val Pro Asn Leu Phe Ile Ser65 70 75 80Ser Leu Ala Leu Gly Asp Leu Leu Leu Leu Ile Thr Cys Ala Pro Val
85 90 95Asp Ala Ser Arg Tyr Leu Ala Asp Arg Trp Leu Phe Gly Arg Ile Gly
100 105 110Cys Lys Leu Ile Pro Phe Ile Gln Leu Thr Ser Val Gly Val Ser Val
115 120 125Phe Thr Leu Thr Ala Leu Ser Ala Asp Arg Tyr Lys Ala Ile Val Arg
130 135 140Pro Met Asp Ile Gln Ala Ser His Ala Leu Met Lys Ile Cys Leu Lys145 150 155 160Ala Ala Phe Ile Trp Ile Ile Ser Met Leu Leu Ala Ile Pro Glu Ala
165 170 175Val Phe Ser Asp Leu His Pro Phe His Glu Glu Ser Thr Asn Gln Thr
180 185 190Phe Ile Ser Cys Ala Pro Tyr Pro His Ser Asn Glu Leu His Pro Lys
195 200 205Ile His Ser Met Ala Ser Phe Leu Val Phe Tyr Val Ile Pro Leu Ser
210 215 220Ile Ile Ser Val Tyr Tyr Tyr Phe Ile Ala Lys Asn Leu Ile Gln Ser225 230 235 240Ala Tyr Asn Leu Pro Val Glu Gly Asn Ile His Val Lys Lys Gln Ile
245 250 255Glu Ser Arg Lys Arg Leu Lys Lys Thr Val Leu Val Phe Val Gly Leu
260 265 270Phe Ala Phe Cys Trp Leu Pro Asn His Val Ile Tyr Leu Tyr Arg Ser
275 280 285Tyr His Tyr Ser Glu Val Asp Thr Ser Met Leu His Phe Val Thr Ser
290 295 300Ile Cys Ala Arg Leu Leu Ala Phe Thr Asn Ser Cys Val Asn Pro Phe305 310 315 320Ala Leu Tyr Leu Leu Ser Lys Ser Phe Arg Lys Gln Phe Asn Thr Gln
325 330 335Leu Leu Cys Cys Gln Pro Gly Leu Ile Ile Arg Ser His Ser Thr Gly
340 345 350Arg Ser Thr Thr Cys Met Thr Ser Leu Lys Ser Thr Asn Pro Ser Val
355 360 365Ala Thr Phe Ser Leu Ile Asn Gly Asn Ile Cys His Glu Arg Tyr Val
370 375 380<210>512<211>1422<212>DNA<213>智人(Homo sapiens)<400>512atgaacactt cagccccacc tgctgtcagc cccaacatca ccgtcctggc accaggaaag 60ggtccctggc aagtggcctt cattgggatc accacgggcc tcctgtcgct agccacagtg 120acaggcaacc tgctggtact catctctttc aaggtcaaca cggagctcaa gacagtcaat 180aactacttcc tgctgagcct ggcctgtgct gacctcatca tcggtacctt ctccatgaac 240ctctatacca cgtacctgct catgggccac tgggctctgg gcacgctggc ttgtgacctc 300tggctggccc tggactatgt ggccagcaat gcctccgtca tgaatctgct gctcatcagc 360tttgaccgct acttctccgt gactcggccc ctgagctacc gtgccaagcg cacaccccgc 420cgggcagctc tgatgatcgg cctggcctgg ctggtttcct ttgtgctctg ggccccagcc 480atcctcttct ggcagtacct ggtaggggag cggacgatgc tagctgggca gtgctacatc 540cagttcctct cccagcccat catcaccttt ggcacagcca tggctgcctt ctacctccct 600gtcacagtca tgtgcacgct ctactggcgc atctaccggg agacagagaa ccgagcacgg 660gagctggcag cccttcaggg ctccgagacg ccaggcaaag ggggtggcag cagcagcagc 720tcagagaggt ctcagccagg ggctgagggc tcaccagaga ctcctccagg ccgctgctgt 780cgctgctgcc gggcccccag gctgctgcag gcctacagct ggaaggaaga agaggaagag 840gacgaaggct ccatggagtc cctcacatcc tcagagggag aggagcctgg ctccgaagtg 900gtgatcaaga tgccaatggt ggaccccgag gcacaggccc ccaccaagca gcccccacgg 960agctccccaa atacagtcaa gaggccgact aagaaagggc gtgatcgagc tggcaagggc 1020cagaagcccc gtggaaagga gcagctggcc aagcggaaga ccttctcgct ggtcaaggag 1080aagaaggcga aacggaccct gagtgccatc ctcctggcct tcatcctcac ctggacaccg 1140tacaacatca tggtgctggt gtccaccttc tgcaaggact gtgttcccga gaccctgtgg 1200gagctgggct actggctgtg ctacgtcaac agcaccatca accccatgtg ctacgcactc 1260tgcaacaaag ccttccggga cacctttcgc ctgctgctgc tttgccgctg ggacaagaga 1320cgctggcgca agatccccaa gcgccctggc tccgtgcacc gcactccctc ccgccaatgc 1380tgatagtccc ctctcctgca tccctccacc ccagtccccg gg 1422<210>513<211>460<212>PRT<213>智人(Homo sapiens)<400>513Met Asn Thr Ser Ala Pro Pro Ala Val Ser Pro Asn Ile Thr Val Leu1 5 10 15Ala Pro Gly Lys Gly Pro Trp Gln Val Ala Phe Ile Gly Ile Thr Thr
20 25 30Gly Leu Leu Ser Leu Ala Thr Val Thr Gly Asn Leu Leu Val Leu Ile
35 40 45Ser Phe Lys Val Asn Thr Glu Leu Lys Thr Val Asn Asn Tyr Phe Leu
50 55 60Leu Ser Leu Ala Cys Ala Asp Leu Ile Ile Gly Thr Phe Ser Met Asn65 70 75 80Leu Tyr Thr Thr Tyr Leu Leu Met Gly His Trp Ala Leu Gly Thr Leu
85 90 95Ala Cys Asp Leu Trp Leu Ala Leu Asp Tyr Val Ala Ser Asn Ala Ser
100 105 110Val Met Asn Leu Leu Leu Ile Ser Phe Asp Arg Tyr Phe Ser Val Thr
115 120 125Arg Pro Leu Ser Tyr Arg Ala Lys Arg Thr Pro Arg Arg Ala Ala Leu
130 135 140Met Ile Gly Leu Ala Trp Leu Val Ser Phe Val Leu Trp Ala Pro Ala145 150 155 160Ile Leu Phe Trp Gln Tyr Leu Val Gly Glu Arg Thr Met Leu Ala Gly
165 170 175Gln Cys Tyr Ile Gln Phe Leu Ser Gln Pro Ile Ile Thr Phe Gly Thr
180 185 190Ala Met Ala Ala Phe Tyr Leu Pro Val Thr Val Met Cys Thr Leu Tyr
195 200 205Trp Arg Ile Tyr Arg Glu Thr Glu Asn Arg Ala Arg Glu Leu Ala Ala
210 215 220Leu Gln Gly Ser Glu Thr Pro Gly Lys Gly Gly Gly Ser Ser Ser Ser225 230 235 240Ser Glu Arg Ser Gln Pro Gly Ala Glu Gly Ser Pro Glu Thr Pro Pro
245 250 255Gly Arg Cys Cys Arg Cys Cys Arg Ala Pro Arg Leu Leu Gln Ala Tyr
260 265 270Ser Trp Lys Glu Glu Glu Glu Glu Asp Glu Gly Ser Met Glu Ser Leu
275 280 285Thr Ser Ser Glu Gly Glu Glu Pro Gly Ser Glu Val Val Ile Lys Met
290 295 300Pro Met Val Asp Pro Glu Ala Gln Ala Pro Thr Lys Gln Pro Pro Arg305 310 315 320Ser Ser Pro Asn Thr Val Lys Arg Pro Thr Lys Lys Gly Arg Asp Arg
325 330 335Ala Gly Lys Gly Gln Lys Pro Arg Gly Lys Glu Gln Leu Ala Lys Arg
340 345 350Lys Thr Phe Ser Leu Val Lys Glu Lys Lys Ala Lys Arg Thr Leu Ser
355 360 365Ala Ile Leu Leu Ala Phe Ile Leu Thr Trp Thr Pro Tyr Asn Ile Met
370 375 380Val Leu Val Ser Thr Phe Cys Lys Asp Cys Val Pro Glu Thr Leu Trp385 390 395 400Glu Leu Gly Tyr Trp Leu Cys Tyr Val Asn Ser Thr Ile Asn Pro Met
405 410 415Cys Tyr Ala Leu Cys Asn Lys Ala Phe Arg Asp Thr Phe Arg Leu Leu
420 425 430Leu Leu Cys Arg Trp Asp Lys Arg Arg Trp Arg Lys Ile Pro Lys Arg
435 440 445Pro Gly Ser Val His Arg Thr Pro Ser Arg Gln Cys
450 455 460<210>514<211>1401<212>DNA<213>智人(Homo sapiens)<400>514atgaataact caacaaactc ctctaacaat agcctggctc ttacaagtcc ttataagaca 60tttgaagtgg tgtttattgt cctggtggct ggatccctca gtttggtgac cattatcggg 120aacatcctag tcatggtttc cattaaagtc aaccgccacc tccagaccgt caacaattac 180tttttattca gcttggcctg tgctgacctt atcataggtg ttttctccat gaacttgtac 240accctctaca ctgtgattgg ttactggcct ttgggacctg tggtgtgtga cctttggcta 300gccctggact atgtggtcag caatgcctca gttatgaatc tgctcatcat cagctttgac 360aggtacttct gtgtcacaaa acctctgacc tacccagtca agcggaccac aaaaatggca 420ggtatgatga ttgcagctgc ctgggtcctc tctttcatcc tctgggctcc agccattctc 480ttctggcagt tcattgtagg ggtgagaact gtggaggatg gggagtgcta cattcagttt 540ttttccaatg ctgctgtcac ctttggtacg gctattgcag ccttctattt gccagtgatc 600atcatgactg tgctatattg gcacatatcc cgagccagca agagcaggat aaagaaggac 660aagaaggagc ctgttgccaa ccaagacccc gtttctccaa gtctggtaca aggaaggata 720gtgaagccaa acaataacaa catgcccagc agtgacgatg gcctggagca caacaaaatc 780cagaatggca aagcccccag ggatcctgtg actgaaaact gtgttcaggg agaggagaag 840gagagctcca atgactccac ctcagtcagt gctgttgcct ctaatatgag agatgatgaa 900ataacccagg atgaaaacac agtttccact tccctgggcc attccaaaga tgagaactct 960aagcaaacat gcatcagaat tggcaccaag accccaaaaa gtgactcatg taccccaact 1020aataccaccg tggaggtagt ggggtcttca ggtcagaatg gagatgaaaa gcagaatatt 1080gtagcccgca agattgtgaa gatgactaag cagcctgcaa aaaagaagcc tcctccttcc 1140cgggaaaaga aagtcaagag gacaatcttg gctattctgt tggctttcat catcacttgg 1200gccccataca atgtcatggt gctcattaac accttttgtg caccttgcat ccccaacact 1260gtgtggacaa ttggttactg gctttgttac atcaacagca ctatcaaccc tgcctgctat 1320gcactttgca atgccacctt caagaagacc tttaaacacc ttctcatgtg tcattataag 1380aacataggcg ctacaaggta a 1401<210>515<211>466<212>PRT<213>智人(Homo sapiens)<400>515Met Asn Asn Ser Thr Asn Ser Ser Asn Asn Ser Leu Ala Leu Thr Ser1 5 10 15Pro Tyr Lys Thr Phe Glu Val Val Phe Ile Val Leu Val Ala Gly Ser
20 25 30Leu Ser Leu Val Thr Ile Ile Gly Asn Ile Leu Val Met Val Ser Ile
35 40 45Lys Val Asn Arg His Leu Gln Thr Val Asn Asn Tyr Phe Leu Phe Ser
50 55 60Leu Ala Cys Ala Asp Leu Ile Ile Gly Val Phe Ser Met Asn Leu Tyr65 70 75 80Thr Leu Tyr Thr Val Ile Gly Tyr Trp Pro Leu Gly Pro Val Val Cys
85 90 95Asp Leu Trp Leu Ala Leu Asp Tyr Val Val Ser Asn Ala Ser Val Met
100 105 110Asn Leu Leu Ile Ile Ser Phe Asp Arg Tyr Phe Cys Val Thr Lys Pro
115 120 125Leu Thr Tyr Pro Val Lys Arg Thr Thr Lys Met Ala Gly Met Met Ile
130 135 140Ala Ala Ala Trp Val Leu Ser Phe Ile Leu Trp Ala Pro Ala Ile Leu145 150 155 160Phe Trp Gln Phe Ile Val Gly Val Arg Thr Val Glu Asp Gly Glu Cys
165 170 175Tyr Ile Gln Phe Phe Ser Asn Ala Ala Val Thr Phe Gly Thr Ala Ile
180 185 190Ala Ala Phe Tyr Leu Pro Val Ile Ile Met Thr Val Leu Tyr Trp His
195 200 205Ile Ser Arg Ala Ser Lys Ser Arg Ile Lys Lys Asp Lys Lys Glu Pro
210 215 220Val Ala Asn Gln Asp Pro Val Ser Pro Ser Leu Val Gln Gly Arg Ile225 230 235 240Val Lys Pro Asn Asn Asn Asn Met Pro Ser Ser Asp Asp Gly Leu Glu
245 250 255His Asn Lys Ile Gln Asn Gly Lys Ala Pro Arg Asp Pro Val Thr Glu
260 265 270Asn Cys Val Gln Gly Glu Glu Lys Glu Ser Ser Asn Asp Ser Thr Ser
275 280 285Val Ser Ala Val Ala Ser Asn Met Arg Asp Asp Glu Ile Thr Gln Asp
290 295 300Glu Asn Thr Val Ser Thr Ser Leu Gly His Ser Lys Asp Glu Asn Ser305 310 315 320Lys Gln Thr Cys Ile Arg Ile Gly Thr Lys Thr Pro Lys Ser Asp Ser
325 330 335Cys Thr Pro Thr Asn Thr Thr Val Glu Val Val Gly Ser Ser Gly Gln
340 345 350Asn Gly Asp Glu Lys Gln Asn Ile Val Ala Arg Lys Ile Val Lys Met
355 360 365Thr Lys Gln Pro Ala Lys Lys Lys Pro Pro Pro Ser Arg Glu Lys Lys
370 375 380Val Lys Arg Thr Ile Leu Ala Ile Leu Leu Ala Phe Ile Ile Thr Trp385 390 395 400Ala Pro Tyr Asn Val Met Val Leu Ile Asn Thr Phe Cys Ala Pro Cys
405 410 415Ile Pro Asn Thr Val Trp Thr Ile Gly Tyr Trp Leu Cys Tyr Ile Asn
420 425 430Ser Thr Ile Asn Pro Ala Cys Tyr Ala Leu Cys Asn Ala Thr Phe Lys
435 440 445Lys Thr Phe Lys His Leu Leu Met Cys His Tyr Lys Asn Ile Gly Ala
450 455 460Thr Arg465<210>516<211>1773<212>DNA<213>智人(Homo sapiens)<400>516atgaccttgc acaataacag tacaacctcg cctttgtttc caaacatcag ctcctcctgg 60atacacagcc cctccgatgc agggctgccc ccgggaaccg tcactcattt cggcagctac 120aatgtttctc gagcagctgg caatttctcc tctccagacg gtaccaccga tgaccctctg 180ggaggtcata ccgtctggca agtggtcttc atcgctttct taacgggcat cctggccttg 240gtgaccatca tcggcaacat cctggtaatt gtgtcattta aggtcaacaa gcagctgaag 300acggtcaaca actacttcct cttaagcctg gcctgtgccg atctgattat cggggtcatt 360tcaatgaatc tgtttacgac ctacatcatc atgaatcgat gggccttagg gaacttggcc 420tgtgacctct ggcttgccat tgactacgta gccagcaatg cctctgttat gaatcttctg 480gtcatcagct ttgacagata cttttccatc acgaggccgc tcacgtaccg agccaaacga 540acaacaaaga gagccggtgt gatgatcggt ctggcttggg tcatctcctt tgtcctttgg 600gctcctgcca tcttgttctg gcaatacttt gttggaaaga gaactgtgcc tccgggagag 660tgcttcattc agttcctcag tgagcccacc attacttttg gcacagccat cgctgctttt 720tatatgcctg tcaccattat gactatttta tactggagga tctataagga aactgaaaag 780cgtaccaaag agcttgctgg cctgcaagcc tctgggacag aggcagagac agaaaacttt 840gtccacccca cgggcagttc tcgaagctgc agcagttacg aacttcaaca gcaaagcatg 900aaacgctcca acaggaggaa gtatggccgc tgccacttct ggttcacaac caagagctgg 960aaacccagct ccgagcagat ggaccaagac cacagcagca gtgacagttg gaacaacaat 1020gatgctgctg cctccctgga gaactccgcc tcctccgacg aggaggacat tggctccgag 1080acgagagcca tctactccat cgtgctcaag cttccgggtc acagcaccat cctcaactcc 1140accaagttac cctcatcgga caacctgcag gtgcctgagg aggagctggg gatggtggac 1200ttggagagga aagccgacaa gctgcaggcc cagaagagcg tggacgatgg aggcagtttt 1260ccaaaaagct tctccaagct tcccatccag ctagagtcag ccgtggacac agctaagact 1320tctgacgtca actcctcagt gggtaagagc acggccactc tacctctgtc cttcaaggaa 1380gccactctgg ccaagaggtt tgctctgaag accagaagtc agatcactaa gcggaaaagg 1440atgtccctgg tcaaggagaa gaaagcgaaa cagaccctca gtgcgatctt gcttgccttc 1500atcatcactt ggaccccata caacatcatg gttctggtga acaccttttg tgacagctgc 1560atacccaaaa ccttttggaa tctgggctac tggctgtgct acatcaacag caccgtgaac 1620cccgtgtgct atgctctgtg caacaaaaca ttcagaacca ctttcaagat gctgctgctg 1680tgccagtgtg acaaaaaaaa gaggcgcaag cagcagtacc agcagagaca gtcggtcatt 1740tttcacaagc gcgcacccga gcaggccttg tag 1773<210>517<211>590<212>PRT<213>智人(Homo sapiens)<400>517Met Thr Leu His Asn Asn Ser Thr Thr Ser Pro Leu Phe Pro Asn Ile1 5 10 15Ser Ser Ser Trp Ile His Ser Pro Ser Asp Ala Gly Leu Pro Pro Gly
20 25 30Thr Val Thr His Phe Gly Ser Tyr Asn Val Ser Arg Ala Ala Gly Asn
35 40 45Phe Ser Ser Pro Asp Gly Thr Thr Asp Asp Pro Leu Gly Gly His Thr
50 55 60Val Trp Gln Val Val Phe Ile Ala Phe Leu Thr Gly Ile Leu Ala Leu65 70 75 80Val Thr Ile Ile Gly Asn Ile Leu Val Ile Val Ser Phe Lys Val Asn
85 90 95Lys Gln Leu Lys Thr Val Asn Asn Tyr Phe Leu Leu Ser Leu Ala Cys
100 105 110Ala Asp Leu Ile Ile Gly Val Ile Ser Met Asn Leu Phe Thr Thr Tyr
115 120 125Ile Ile Met Asn Arg Trp Ala Leu Gly Asn Leu Ala Cys Asp Leu Trp
130 135 140Leu Ala Ile Asp Tyr Val Ala Ser Asn Ala Ser Val Met Asn Leu Leu145 150 155 160Val Ite Ser Phe Asp Arg Tyr Phe Ser Ile Thr Arg Pro Leu Thr Tyr
165 170 175Arg Ala Lys Arg Thr Thr Lys Arg Ala Gly Val Met Ile Gly Leu Ala
180 185 190Trp Val Ile Ser Phe Val Leu Trp Ala Pro Ala Ile Leu Phe Trp Gln
195 200 205Tyr Phe Val Gly Lys Arg Thr Val Pro Pro Gly Glu Cys Phe Ile Gln
210 215 220Phe Leu Ser Glu Pro Thr Ile Thr Phe Gly Thr Ala Ile Ala Ala Phe225 230 235 240Tyr Met Pro Val Thr Ile Met Thr Ile Leu Tyr Trp Arg Ile Tyr Lys
245 250 255Glu Thr Glu Lys Arg Thr Lys Glu Leu Ala Gly Leu Gln Ala Ser Gly
260 265 270Thr Glu Ala Glu Thr Glu Asn Phe Val His Pro Thr Gly Ser Ser Arg
275 280 285Ser Cys Ser Ser Tyr Glu Leu Gln Gln Gln Ser Met Lys Arg Ser Asn
290 295 300Arg Arg Lys Tyr Gly Arg Cys His Phe Trp Phe Thr Thr Lys Ser Trp305 310 315 320Lys Pro Ser Ser Glu Gln Met Asp Gln Asp His Ser Ser Ser Asp Ser
325 330 335Trp Asn Asn Asn Asp Ala Ala Ala Ser Leu Glu Asn Ser Ala Ser Ser
340 345 350Asp Glu Glu Asp Ile Gly Ser Glu Thr Arg Ala Ile Tyr Ser Ile Val
355 360 365Leu Lys Leu Pro Gly His Ser Thr Ile Leu Asn Ser Thr Lys Leu Pro
370 375 380Ser Ser Asp Asn Leu Gln Val Pro Glu Glu Glu Leu Gly Met Val Asp385 390 395 400Leu Glu Arg Lys Ala Asp Lys Leu Gln Ala Gln Lys Ser Val Asp Asp
405 410 415Gly Gly Ser Phe Pro Lys Ser Phe Ser Lys Leu Pro Ile Gln Leu Glu
420 425 430Ser Ala Val Asp Thr Ala Lys Thr Ser Asp Val Asn Ser Ser Val Gly
435 440 445Lys Ser Thr Ala Thr Leu Pro Leu Ser Phe Lys Glu Ala Thr Leu Ala
450 455 460Lys Arg Phe Ala Leu Lys Thr Arg Ser Gln Ile Thr Lys Arg Lys Arg465 470 475 480Met Ser Leu Val Lys Glu Lys Lys Ala Lys Gln Thr Leu Ser Ala Ile
485 490 495Leu Leu Ala Phe Ile Ile Thr Trp Thr Pro Tyr Asn Ile Met Val Leu
500 505 510Val Asn Thr Phe Cys Asp Ser Cys Ile Pro Lys Thr Phe Trp Asn Leu
515 520 525Gly Tyr Trp Leu Cys Tyr Ile Asn Ser Thr Val Asn Pro Val Cys Tyr
530 535 540Ala Leu Cys Asn Lys Thr Phe Arg Thr Thr Phe Lys Met Leu Leu Leu545 550 555 560Cys Gln Cys Asp Lys Lys Lys Arg Arg Lys Gln Gln Tyr Gln Gln Arg
565 570 575Gln Ser Val Ile Phe His Lys Arg Ala Pro Glu Gln Ala Leu
580 585 590<210>518<211>1440<212>DNA<213>智人(Homo sapiens)<400>518atggccaact tcacacctgt caatggcagc tcgggcaatc agtccgtgcg cctggtcacg 60tcatcatccc acaatcgcta tgagacggtg gaaatggtct tcattgccac agtgacaggc 120tccctgagcc tggtgactgt cgtgggcaac atcctggtga tgctgtccat caaggtcaac 180aggcagctgc agacagtcaa caactacttc ctcttcagcc tggcgtgtgc tgatctcatc 240ataggcgcct tctccatgaa cctctacacc gtgtacatca tcaagggcta ctggcccctg 300ggcgccgtgg tctgcgacct gtggctggcc ctggactacg tggtgagcaa cgcctccgtc 360atgaaccttc tcatcatcag ctttgaccgc tacttctgcg tcaccaagcc tctcacctac 420cctgcccggc gcaccaccaa gatggcaggc ctcatgattg ctgctgcctg ggtactgtcc 480ttcgtgctct gggcgcctgc catcttgttc tggcagtttg tggtgggtaa gcggacggtg 540cccgacaacc agtgcttcat ccagttcctg tccaacccag cagtgacctt tggcacagcc 600attgctgcct tctacctgcc tgtggtcatc atgacggtgc tgtacatcca catctccctg 660gccagtcgca gccgagtcca caagcaccgg cccgagggcc cgaaggagaa gaaagccaag 720acgctggcct tcctcaagag cccactaatg aagcagagcg tcaagaagcc cccgcccggg 780gaggccgccc gggaggagct gcgcaatggc aagctggagg aggccccccc gccagcgctg 840ccaccgccac cgcgccccgt ggctgataag gacacttcca atgagtccag ctcaggcagt 900gccacccaga acaccaagga acgcccagcc acagagctgt ccaccacaga ggccaccacg 960cccgccatgc ccgcccctcc cctgcagccg cgggccctca acccagcctc cagatggtcc 1020aagatccaga ttgtgacgaa gcagacaggc aatgagtgtg tgacagccat tgagattgtg 1080cctgccacgc cggctggcat gcgccctgcg gccaacgtgg cccgcaagtt cgccagcatc 1140gctcgcaacc aggtgcgcaa gaagcggcag atggcggccc gggagcgcaa agtgaaacga 1200acgatctttg ccattctgct agccttcatc ctcacctgga cgccctacaa cgtcatggtc 1260ctggtgaaca ccttctgcca gagctgcatc cctgacacgg tgtggtccat tggctactgg 1320ctctgctacg tcaacagcac catcaaccct gcctgctatg ctctgtgcaa cgccaccttt 1380aaaaagacct tccggcacct gctgctgtgc cagtatcgga acatcggcac tgccaggtag 1440<210>519<211>479<212>PRT<213>智人(Homo sapiens)<400>519Met Ala Asn Phc Thr Pro Val Asn Gly Ser Ser Gly Asn Gln Ser Val1 5 10 15Arg Leu Val Thr Ser Ser Ser His Asn Arg Tyr Glu Thr Val Glu Met
20 25 30Val Phc Ile Ala Thr Val Thr Gly Ser Leu Ser Leu Val Thr Val Val
35 40 45Gly Asn Ile Leu Val Met Leu Ser Ile Lys Val Asn Arg Gln Leu Gln
50 55 60Thr Val Asn Asn Tyr Phe Leu Phe Ser Leu Ala Cys Ala Asp Leu Ile65 70 75 80Ile Gly Ala Phe Ser Met Asn Leu Tyr Thr Val Tyr Ile Ile Lys Gly
85 90 95Tyr Trp Pro Leu Gly Ala Val Val Cys Asp Leu Trp Leu Ala Leu Asp
100 105 110Tyr Val Val Ser Asn Ala Ser Val Met Asn Leu Leu Ile Ile Ser Phe
115 120 125Asp Arg Tyr Phe Cys Val Thr Lys Pro Leu Thr Tyr Pro Ala Arg Arg
130 135 140Thr Thr Lys Met Ala Gly Leu Met Ile Ala Ala Ala Trp Val Leu Ser145 150 155 160Phe Val Leu Trp Ala Pro Ala Ile Leu Phe Trp Gln Phe Val Val Gly
165 170 175Lys Arg Thr Val Pro Asp Asn Gln Cys Phe Ile Gln Phe Leu Ser Asn
180 185 190Pro Ala Val Thr Phe Gly Thr Ala Ile Ala Ala Phe Tyr Leu Pro Val
195 200 205Val Ile Met Thr Val Leu Tyr Ile His Ile Ser Leu Ala Ser Arg Ser
210 215 220Arg Val His Lys His Arg Pro Glu Gly Pro Lys Glu Lys Lys Ala Lys225 230 235 240Thr Leu Ala Phe Leu Lys Ser Pro Leu Met Lys Gln Ser Val Lys Lys
245 250 255Pro Pro Pro Gly Glu Ala Ala Arg Glu Glu Leu Arg Asn Gly Lys Leu
260 265 270Glu Glu Ala Pro Pro Pro Ala Leu Pro Pro Pro Pro Arg Pro Val Ala
275 280 285Asp Lys Asp Thr Ser Asn Glu Ser Ser Ser Gly Ser Ala Thr Gln Asn
290 295 300Thr Lys Glu Arg Pro Ala Thr Glu Leu Ser Thr Thr Glu Ala Thr Thr305 310 315 320Pro Ala Met Pro Ala Pro Pro Leu Gln Pro Arg Ala Leu Asn Pro Ala
325 330 335Ser Arg Trp Ser Lys Ile Gln Ile Val Thr Lys Gln Thr Gly Asn Glu
340 345 350Cys Val Thr Ala Ile Glu Ile Val Pro Ala Thr Pro Ala Gly Met Arg
355 360 365Pro Ala Ala Asn Val Ala Arg Lys Phe Ala Ser Ile Ala Arg Asn Gln
370 375 380Val Arg Lys Lys Arg Gln Met Ala Ala Arg Glu Arg Lys Val Lys Arg385 390 395 400Thr Ile Phe Ala Ile Leu Leu Ala Phe Ile Leu Thr Trp Thr Pro Tyr
405 410 415Asn Val Met Val Leu Val Asn Thr Phe Cys Gln Ser Cys Ile Pro Asp
420 425 430Thr Val Trp Ser Ile Gly Tyr Trp Leu Cys Tyr Val Asn Ser Thr Ile
435 440 445Asn Pro Ala Cys Tyr Ala Leu Cys Asn Ala Thr Phe Lys Lys Thr Phe
450 455 460Arg His Leu Leu Leu Cys Gln Tyr Arg Asn Ile Gly Thr Ala Arg465 470 475<210>520<211>1599<212>DNA<213>智人(Homo sapiens)<400>520atggaagggg attcttacca caatgcaacc accgtcaatg gcaccccagt aaatcaccag 60cctttggaac gccacaggtt gtgggaagtc atcaccattg cagctgtgac tgctgtggta 120agcctgatca ccattgtggg caatgtcttg gtcatgatct ccttcaaagt caacagccag 180ctcaagacag ttaacaacta ttacctgctc agcttagcct gtgcagatct catcattgga 240atcttctcca tgaacctcta caccacctac atcctcatgg gacgctgggc tctcgggagt 300ctggcttgtg acctttggct tgcactggac tacgtggcca gcaacgcttc tgtcatgaac 360cttctggtga tcagttttga ccgttacttt tccatcacaa gacccttgac atatcgggcc 420aagcgtactc cgaaaagggc tggcatcatg attggcttgg cctggctgat ctccttcatc 480ctctgggccc cagcaatcct ctgctggcag tacttggttg ggaagcggac agttccactg 540gatgagtgcc agatccagtt tctctctgag cccaccatca cttttggcac tgccattgct 600gccttctaca tccctgtttc tgtcatgacc atcctctact gtcgaatcta ccgggaaaca 660gagaagcgaa ccaaggacct ggctgacctc cagggttctg actctgtgac caaagctgag 720aagagaaagc cagctcatag ggctctgttc agatcctgct tgcgctgtcc tcgacccacc 780ctggcccagc gggaaaggaa ccaggcctcc tggtcatcct cccgcaggag cacctccacc 840actgggaagc catcccaagc cactggccca agcgccaatt gggccaaagc tgagcagctc 900accacctgta gcagctaccc ttcctcagag gatgaggaca agcccgccac tgaccctgtc 960ctccaagtgg tctacaagag tcagggtaag gaaagcccag gggaagaatt cagtgctgaa 1020gagactgagg aaacttttgt gaaagctgaa actgaaaaaa gtgactatga caccccaaac 1080taccttctgt ctccagcagc tgctcataga cccaagagtc agaaatgtgt ggcctataag 1140ttccgattgg tggtaaaagc tgacgggaac caggagacca acaatggctg tcacaaggtg 1200aaaatcatgc cctgcccctt cccagtggcc aaggaacctt caacgaaagg cctcaatccc 1260aaccccagcc atcaaatgac caaacgaaag agagtggtcc tagtcaaaga gaggaaagca 1320aaacagacac tgagtgccat tctcctggcc ttcatcatca catggacccc gtataacatc 1380atggtcctgg tttctacctt ctgtgacaag tgtgtcccag tcaccctgtg gcacttgggc 1440tattggttgt gctatgtcaa tagcactgtc aaccccatct gctatgccct ctgcaacaga 1500accttcagga agacctttaa gatgctgctt ctctgccgat ggaaaaagaa aaaagtggaa 1560gagaagttgt actggcaggg gaacagcaag ctaccctga 1599<210>521<211>532<212>PRT<213>智人(Homo sapiens)<400>521Met Glu Gly Asp Ser Tyr His Asn Ala Thr Thr Val Asn Gly Thr Pro1 5 10 15Val Asn His Gln Pro Leu Glu Arg His Arg Leu Trp Glu Val Ile Thr
20 25 30Ile Ala Ala Val Thr Ala Val Val Ser Leu Ile Thr Ile Val Gly Asn
35 40 45Val Leu Val Met Ile Ser Phe Lys Val Asn Ser Gln Leu Lys Thr Val
50 55 60Asn Asn Tyr Tyr Leu Leu Ser Leu Ala Cys Ala Asp Leu Ile Ile Gly65 70 75 80Ile Phe Ser Met Asn Leu Tyr Thr Thr Tyr Ile Leu Met Gly Arg Trp
85 90 95Ala Leu Gly Ser Leu Ala Cys Asp Leu Trp Leu Ala Leu Asp Tyr Val
100 105 110Ala Ser Asn Ala Ser Val Met Asn Leu Leu Val Ile Ser Phe Asp Arg
115 120 125Tyr Phe Ser Ile Thr Arg Pro Leu Thr Tyr Arg Ala Lys Arg Thr Pro
130 135 140Lys Arg Ala Gly Ile Met Ile Gly Leu Ala Trp Leu Ile Ser Phe Ile145 150 155 160Leu Trp Ala Pro Ala Ile Leu Cys Trp Gln Tyr Leu Val Gly Lys Arg
165 170 175Thr Val Pro Leu Asp Glu Cys Gln Ile Gln Phe Leu Ser Glu Pro Thr
180 185 190Ile Thr Phe Gly Thr Ala Ile Ala Ala Phe Tyr Ile Pro Val Ser Val
195 200 205Met Thr Ile Leu Tyr Cys Arg Ile Tyr Arg Glu Thr Glu Lys Arg Thr
210 215 220Lys Asp Leu Ala Asp Leu Gln Gly Ser Asp Ser Val Thr Lys Ala Glu225 230 235 240Lys Arg Lys Pro Ala His Arg Ala Leu Phe Arg Ser Cys Leu Arg Cys
245 250 255Pro Arg Pro Thr Leu Ala Gln Arg Glu Arg Asn Gln Ala Ser Trp Ser
260 265 270Ser Ser Arg Arg Ser Thr Ser Thr Thr Gly Lys Pro Ser Gln Ala Thr
275 280 285Gly Pro Ser Ala Asn Trp Ala Lys Ala Glu Gln Leu Thr Thr Cys Ser
290 295 300Ser Tyr Pro Ser Ser Glu Asp Glu Asp Lys Pro Ala Thr Asp Pro Val305 310 315 320Leu Gln Val Val Tyr Lys Ser Gln Gly Lys Glu Ser Pro Gly Glu Glu
325 330 335Phe Ser Ala Glu Glu Thr Glu Glu Thr Phe Val Lys Ala Glu Thr Glu
340 345 350Lys Ser Asp Tyr Asp Thr Pro Asn Tyr Leu Leu Ser Pro Ala Ala Ala
355 360 365His Arg Pro Lys Ser Gln Lys Cys Val Ala Tyr Lys Phe Arg Leu Val
370 375 380Val Lys Ala Asp Gly Asn Gln Glu Thr Asn Asn Gly Cys His Lys Val385 390 395 400Lys Ile Met Pro Cys Pro Phe Pro Val Ala Lys Glu Pro Ser Thr Lys
405 410 415Gly Leu Asn Pro Asn Pro Ser His Gln Met Thr Lys Arg Lys Arg Val
420 425 430Val Leu Val Lys Glu Arg Lys Ala Lys Gln Thr Leu Ser Ala Ile Leu
435 440 445Leu Ala Phe Ile Ile Thr Trp Thr Pro Tyr Asn Ile Met Val Leu Val
450 455 460Ser Thr Phe Cys Asp Lys Cys Val Pro Val Thr Leu Trp His Leu Gly465 470 475 480Tyr Trp Leu Cys Tyr Val Asn Ser Thr Val Asn Pro Ile Cys Tyr Ala
485 490 495Leu Cys Asn Arg Thr Phe Arg Lys Thr Phe Lys Met Leu Leu Leu Cys
500 505 510Arg Trp Lys Lys Lys Lys Val Glu Glu Lys Leu Tyr Trp Gln Gly Asn
515 520 525Ser Lys Leu Pro
530<210>522<21l>972<212>DNA<213>智人(Homo sapiens)<400>522atgaatgctt cgtgctgcct gccctctgtt cagccaacac tgcctaatgg ctcggagcac 60ctccaagccc ctttcttcag caaccagagc agcagcgcct tctgtgagca ggtcttcatc 120aagcccgaga ttttcctgtc tctgggcatc gtcagtctgc tggaaaacat cctggttatc 180ctggccgtgg tcaggaacgg caacctgcac tccccgatgt acttctttct ctgcagcctg 240gcggtggccg acatgctggt aagtgtgtcc aatgccctgg agaccatcat gatcgccatc 300gtccacagcg actacctgac cttcgaggac cagtttatcc agcacatgga caacatcttc 360gactccatga tctgcatctc cctggtggcc tccatctgca acctcctggc catcgccgtc 420gacaggtacg tcaccatctt ttacgcgctc cgctaccaca gcatcatgac cgtgaggaag 480gccctcacct tgatcgtggc catctgggtc tgctgcggcg tctgtggcgt ggtgttcatc 540gtctactcgg agagcaaaat ggtcattgtg tgcctcatca ccatgttctt cgccatgatg 600ctcctcatgg gcaccctcta cgtgcacatg ttcctctttg cgcggctgca cgtcaagcgc 660atagcagcac tgccacctgc cgacggggtg gccccacagc aacactcatg catgaagggg 720aaagtcacca tcaccattct cctgggcgtg ttcatcttct gctgggcccc cttcttcctc 780cacctggtcc tcatcatcac ctgccccacc aacccctact gcatctgcta cactgcccac 840ttcaacacct acctggtcct catcatgtgc aactccgtca tcgacccact catctacgct 900ttccggagcc tggaattgcg caacaccttt agggagattc tctgtggctg caacggcatg 960aacttgggat ag 972<210>523<211>323<212>PRT<213>智人(Homo sapiens)<400>523Met Asn Ala Ser Cys Cys Leu Pro Ser Val Gln Pro Thr Leu Pro Asn1 5 10 15Gly Ser Glu His Leu Gln Ala Pro Phe Phe Ser Asn Gln Ser Ser Ser
20 25 30Ala Phe Cys Glu Gln Val Phe Ile Lys Pro Glu Ile Phe Leu Ser Leu
35 40 45Gly Ile Val Ser Leu Leu Glu Asn Ile Leu Val Ile Leu Ala Val Val
50 55 60Arg Asn Gly Asn Leu His Ser Pro Met Tyr Phe Phe Leu Cys Ser Leu65 70 75 80Ala Val Ala Asp Met Leu Val Ser Val Ser Asn Ala Leu Glu Thr Ile
85 90 95Met Ile Ala Ile Val His Ser Asp Tyr Leu Thr Phe Glu Asp Gln Phe
100 105 110Ile Gln His Met Asp Asn Ile Phe Asp Ser Met Ile Cys Ile Ser Leu
115 120 125Val Ala Ser Ile Cys Asn Leu Leu Ala Ile Ala Val Asp Arg Tyr Val
130 135 140Thr Ile Phe Tyr Ala Leu Arg Tyr His Ser Ile Met Thr Val Arg Lys145 150 155 160Ala Leu Thr Leu Ile Val Ala Ile Trp Val Cys Cys Gly Val Cys Gly
165 170 175Val Val Phe Ile Val Tyr Ser Glu Ser Lys Met Val Ile Val Cys Leu
180 185 190Ile Thr Met Phe Phe Ala Met Met Leu Leu Met Gly Thr Leu Tyr Val
195 200 205His Met Phe Leu Phe Ala Arg Leu His Val Lys Arg Ile Ala Ala Leu
210 215 220Pro Pro Ala Asp Gly Val Ala Pro Gln Gln His Ser Cys Met Lys Gly225 230 235 240Lys Val Thr Ile Thr Ile Leu Leu Gly Val Phe Ile Phe Cys Trp Ala
245 250 255Pro Phe Phe Leu His Leu Val Leu Ile Ile Thr Cys Pro Thr Asn Pro
260 265 270Tyr Cys Ile Cys Tyr Thr Ala His Phe Asn Thr Tyr Leu Val Leu Ile
275 280 285Met Cys Asn Ser Val Ile Asp Pro Leu Ile Tyr Ala Phe Arg Ser Leu
290 295 300Glu Leu Arg Asn Thr Phe Arg Glu Ile Leu Cys Gly Cys Asn Gly Met305 310 315 320Asn Leu Gly<210>524<211>1224<212>DNA<213>智人(Homo sapiens)<400>524atggataacg tcctcccggt ggactcagac ctctccccaa acatctccac taacacctcg 60gaacccaatc agttcgtgca accagcctgg caaattgtcc tttgggcagc tgcctacacg 120gtcattgtgg tgacctctgt ggtgggcaac gtggtagtga tgtggatcat cttagcccac 180aaaagaatga ggacagtgac gaactatttt ctggtgaacc tggccttcgc ggaggcctcc 240atggctgcat tcaatacagt ggtgaacttc acctatgctg tccacaacga atggtactac 300ggcctgttct actgcaagtt ccacaacttc tttcccatcg ccgctgtctt cgccagtatc 360tactccatga cggctgtggc ctttgatagg tacatggcca tcatacatcc cctccagccc 420cggctgtcag ccacagccac caaagtggtc atctgtgtca tctgggtcct ggctctcctg 480ctggccttcc cccagggcta ctactcaacc acagagacca tgcccagcag agtcgtgtgc 540atgatcgaat ggccagagca tccgaacaag atttatgaga aagtgtacca catctgtgtg 600actgtgctga tctacttcct ccccctgctg gtgattggct atgcatacac cgtagtggga 660atcacactat gggccagtga gatccccggg gactcctctg accgctacca cgagcaagtc 720tctgccaagc gcaaggtgaa gaaaatgatg attgtcgtgg tgtgcacctt cgccatctgc 780tggctgccct tccacatctt cttcctcctg ccctacatca acccagatct ctacctgaag 840aagtttatcc agcaggtcta cctggccatc atgtggctgg ccatgagctc caccatgtac 900aaccccatca tctactgctg cctcaatgac aggttccgtc tgggcttcaa gcatgccttc 960cggtgctgcc ccttcatcag cgccggcgac tatgaggggc tggaaatgaa atccacccgg 1020tatctccaga cccagggcag tgtgtacaaa gtcagccgcc tggagaccac catctccaca 1080gtggtggggg cccacgagga ggagccagag gacggcccca aggccacacc ctcgtccctg 1140gacctgacct ccaactgctc ttcacgaagt gactccaaga ccatgacaga gagcttcagc 1200ttctcctcca atgtgctctc ctag 1224<210>525<211>407<212>PRT<213>智人(Homo sapiens)<400>525Met Asp Asn Val Leu Pro Val Asp Ser Asp Leu Ser Pro Asn Ile Ser1 5 10 15Thr Asn Thr Ser Glu Pro Asn Gln Phe Val Gln Pro Ala Trp Gln Ile
20 25 30Val Leu Trp Ala Ala Ala Tyr Thr Val Ile Val Val Thr Ser Val Val
35 40 45Gly Asn Val Val Val Met Trp Ile Ile Leu Ala His Lys Arg Met Arg
50 55 60Thr Val Thr Asn Tyr Phe Leu Val Asn Leu Ala Phe Ala Glu Ala Ser65 70 75 80Met Ala Ala Phe Asn Thr Val Val Asn Phe Thr Tyr Ala Val His Asn
85 90 95Glu Trp Tyr Tyr Gly Leu Phe Tyr Cys Lys Phe His Asn Phe Phe Pro
100 105 110Ile Ala Ala Val Phe Ala Ser Ile Tyr Ser Met Thr Ala Val Ala Phe
115 120 125Asp Arg Tyr Met Ala Ile Ile His Pro Leu Gln Pro Arg Leu Ser Ala
130 135 140Thr Ala Thr Lys Val Val Ile Cys Val Ile Trp Val Leu Ala Leu Leu145 150 155 160Leu Ala Phe Pro Gln Gly Tyr Tyr Ser Thr Thr Glu Thr Met Pro Ser
165 170 175Arg Val Val Cys Met Ile Glu Trp Pro Glu His Pro Asn Lys Ile Tyr
180 185 190Glu Lys Val Tyr His Ile Cys Val Thr Val Leu Ile Tyr Phe Leu Pro
195 200 205Leu Leu Val Ile Gly Tyr Ala Tyr Thr Val Val Gly Ile Thr Leu Trp
210 215 220Ala Ser Glu Ile Pro Gly Asp Ser Ser Asp Arg Tyr His Glu Gln Val225 230 235 240Ser Ala Lys Arg Lys Val Lys Lys Met Met Ile Val Val Val Cys Thr
245 250 255Phe Ala Ile Cys Trp Leu Pro Phe His Ile Phe Phe Leu Leu Pro Tyr
260 265 270Ile Asn Pro Asp Leu Tyr Leu Lys Lys Phe Ile Gln Gln Val Tyr Leu
275 280 285Ala Ile Met Trp Leu Ala Met Ser Ser Thr Met Tyr Asn Pro Ile Ile
290 295 300Tyr Cys Cys Leu Asn Asp Arg Phe Arg Leu Gly Phe Lys His Ala Phe305 310 315 320Arg Cys Cys Pro Phe Ile Ser Ala Gly Asp Tyr Glu Gly Leu Glu Met
325 330 335Lys Ser Thr Arg Tyr Leu Gln Thr Gln Gly Ser Val Tyr Lys Val Ser
340 345 350Arg Leu Glu Thr Thr Ile Ser Thr Val Val Gly Ala His Glu Glu Glu
355 360 365Pro Glu Asp Gly Pro Lys Ala Thr Pro Ser Ser Leu Asp Leu Thr Ser
370 375 380Asn Cys Ser Ser Arg Ser Asp Ser Lys Thr Met Thr Glu Ser Phe Ser385 390 395 400Phe Ser Ser Asn Val Leu Ser
405<210>526<211>1197<212>DNA<213>智人(Homo sapiens)<400>526atggggacct gtgacattgt gactgaagcc aatatctcat ctggccctga gagcaacacc 60acgggcatca cagccttctc catgcccagc tggcagctgg cactgtgggc accagcctac 120ctggccctgg tgctggtggc cgtgacgggt aatgccatcg tcatctggat catcctggcc 180catcggagga tgcgcacagt caccaactac ttcatcgtca atctggcgct ggctgacctc 240tgcatggctg ccttcaatgc cgccttcaac tttgtctatg ccagccacaa catctggtac 300tttggccgtg ccttctgcta cttccagaac ctcttcccca tcacagccat gtttgtcagc 360atctactcca tgaccgccat tgctgccgac aggtacatgg ccatcgtcca ccccttccag 420cctcggcttt cagctcccag caccaaggcg gttattgctg gcatctggct ggtggctctc 480gccctggcct cccctcagtg cttctactcc accgtcacca tggaccaggg tgccaccaag 540tgcgtggtgg cctggcccga agacagcggg ggcaagacgc tcctcctgta ccacctcgtg 600gtgatcgccc tcatctactt cctgccgctc gcggtgatgt ttgtagccta cagcgtcatc 660ggcctcacgc tctggaggcg cgcagtgccc ggacatcagg cgcacggtgc caacctccgc 720catctgcagg ccaagaagaa gtttaagaag accatggtgc tggtggtgct gacgtttgcc 780atctgctggc tgccctacca cctctacttc atcctgggca gcttccagga ggacatctac 840tgccacaagt tcatccagca agtctacctg gcactcttct ggttggccat gagctctacc 900atgtacaatc ccatcatcta ctgctgtctc aaccacaggt ttcgctctgg gttccggctt 960gccttccgct gctgcccatg ggtcacaccc accaaggaag ataagctcga gctgactccc 1020acgacctccc tctccacgag agtcaacagg tgtcacacta aggagacttt gttcatggct 1080ggggacacag ccccctccga ggctaccagt ggggaggcgg ggcgtcccca ggatggatca 1140gggctatggt ttgggtatgg tttgcttgcc cccaccaaaa ctcatgttga aatttga 1197<210>527<211>398<212>PRT<213>智人(Homo sapiens)<400>527Met Gly Thr Cys Asp Ile Val Thr Glu Ala Asn Ile Ser Ser Gly Pro1 5 10 15Glu Ser Asn Thr Thr Gly Ile Thr Ala Phe Ser Met Pro Ser Trp Gln
20 25 30Leu Ala Leu Trp Ala Pro Ala Tyr Leu Ala Leu Val Leu Val Ala Val
35 40 45Thr Gly Asn Ala Ile Val Ile Trp Ile Ile Leu Ala His Arg Arg Met
50 55 60Arg Thr Val Thr Asn Tyr Phe Ile Val Asn Leu Ala Leu Ala Asp Leu65 70 75 80Cys Met Ala Ala Phe Asn Ala Ala Phe Asn Phe Val Tyr Ala Ser His
85 90 95Asn Ile Trp Tyr Phe Gly Arg Ala Phe Cys Tyr Phe Gln Asn Leu Phe
100 105 110Pro Ile Thr Ala Met Phe Val Ser Ile Tyr Ser Met Thr Ala Ile Ala
115 120 125Ala Asp Arg Tyr Met Ala Ile Val His Pro Phe Gln Pro Arg Leu Ser
130 135 140Ala Pro Ser Thr Lys Ala Val Ile Ala Gly Ile Trp Leu Val Ala Leu145 150 155 160Ala Leu Ala Ser Pro Gln Cys Phe Tyr Ser Thr Val Thr Met Asp Gln
165 170 175Gly Ala Thr Lys Cys Val Val Ala Trp Pro Glu Asp Ser Gly Gly Lys
180 185 190Thr Leu Leu Leu Tyr His Leu Val Val Ile Ala Leu Ile Tyr Phe Leu
195 200 205Pro Leu Ala Val Met Phe Val Ala Tyr Ser Val Ile Gly Leu Thr Leu
210 215 220Trp Arg Arg Ala Val Pro Gly His Gln Ala His Gly Ala Asn Leu Arg225 230 235 240His Leu Gln Ala Lys Lys Lys Phe Lys Lys Thr Met Val Leu Val Val
245 250 255Leu Thr Phe Ala Ile Cys Trp Leu Pro Tyr His Leu Tyr Phe Ile Leu
260 265 270Gly Ser Phe Gln Glu Asp Ile Tyr Cys His Lys Phe Ile Gln Gln Val
275 280 285Tyr Leu Ala Leu Phe Trp Leu Ala Met Ser Ser Thr Met Tyr Asn Pro
290 295 300Ile Ile Tyr Cys Cys Leu Asn His Arg Phe Arg Ser Gly Phe Arg Leu305 310 315 320Ala Phe Arg Cys Cys Pro Trp Val Thr Pro Thr Lys Glu Asp Lys Leu
325 330 335Glu Leu Thr Pro Thr Thr Ser Leu Ser Thr Arg Val Asn Arg Cys His
340 345 350Thr Lys Glu Thr Leu Phe Met Ala Gly Asp Thr Ala Pro Ser Glu Ala
355 360 365Thr Ser Gly Glu Ala Gly Arg Pro Gln Asp Gly Ser Gly Leu Trp Phe
370 375 380Gly Tyr Gly Leu Leu Ala Pro Thr Lys Thr His Val Glu Ile385 390 395<210>528<211>1398<212>DNA<213>智人(Homo sapiens)<400>528atggccactc tcccagcagc agaaacctgg atagacgggg gtggaggcgt gggtgcagac 60gccgtgaacc tgaccgcctc gctagctgcc ggggcggcca cgggggcagt tgagactggg 120tggctgcaac tgctggacca agctggcaac ctctcctcct ccccttccgc gctgggactg 180cctgtggctt cccccgcgcc ctcccagccc tgggccaacc tcaccaacca gttcgtgcag 240ccgtcctggc gcatcgcgct ctggtccctg gcgtatggtg tggtggtggc agtggcagtt 300ttgggaaatc tcatcgtcat ctggatcatc ctggcccaca agcgcatgag gactgtcacc 360aactacttcc ttgtgaacct ggctttctcc gacgcctcca tggccgcctt caacacgttg 420gtcaatttca tctacgcgct tcatagcgag tggtactttg gcgccaacta ctgccgcttc 480cagaacttct ttcctatcac agctgtgttc gccagcatct actccatgac ggccattgcg 540gtggacaggt atatggctat tattgatccc ttgaaaccca gactgtctgc tacagcaacc 600aagattgtca ttggaagtat ttggattcta gcatttctac ttgccttccc tcagtgtctt 660tattccaaaa ccaaagtcat gccaggccgt actctctgct ttgtgcaatg gccagaaggt 720cccaaacaac atttcactta ccatattatc gtcattatac tggtgtactg tttcccattg 780ctcatcatgg gtattacata caccattgtt ggaattactc tctggggagg agaaatccca 840ggagatacct gtgacaagta tcatgagcag ctaaaggcca aaagaaaggt taagaaaatg 900atgattattg ttgtcatgac atttgctatc tgctggctgc cctatcatat ttacttcatt 960ctcactgcaa tctatcaaca actaaataga tggaaataca tccagcaggt ctacctggct 1020agcttttggc tggcaatgag ctcaaccatg tacaatccca tcatctactg ctgtctgaat 1080aaaagatttc gagctggctt caagagagca tttcgctggt gtcctttcat caaagtttcc 1140agctatgatg agctagagct caagaccacc aggtttcatc caaaccggca aagcagtatg 1200tacaccgtga ccagaatgga gtccatgaca gtcgtgtttg accccaacga tgcagacacc 1260accaggtcca gtcggaagaa aagagcaacg ccaagagacc caagtttcaa tggctgctct 1320cgcaggaatt ccaaatctgc ctccgccact tcaagtttca taagctcacc ctatacctct 1380gtggatgaat attcttaa 1398<210>529<211>465<212>PRT<213>智人(Homo sapiens)<400>529Met Ala Thr Leu Pro Ala Ala Glu Thr Trp Ile Asp Gly Gly Gly Gly1 5 10 15Val Gly Ala Asp Ala Val Asn Leu Thr Ala Ser Leu Ala Ala Gly Ala
20 25 30Ala Thr Gly Ala Val Glu Thr Gly Trp Leu Gln Leu Leu Asp Gln Ala
35 40 45Gly Asn Leu Ser Ser Ser Pro Ser Ala Leu Gly Leu Pro Val Ala Ser
50 55 60Pro Ala Pro Ser Gln Pro Trp Ala Asn Leu Thr Asn Gln Phe Val Gln65 70 75 80Pro Ser Trp Arg Ile Ala Leu Trp Ser Leu Ala Tyr Gly Val Val Val
85 90 95Ala Val Ala Val Leu Gly Asn Leu Ile Val Ile Trp Ile Ile Leu Ala
100 105 110His Lys Arg Met Arg Thr Val Thr Asn Tyr Phe Leu Val Asn Leu Ala
115 120 125Phe Ser Asp Ala Ser Met Ala Ala Phe Asn Thr Leu Val Asn Phe Ile
130 135 140Tyr Ala Leu His Ser Glu Trp Tyr Phe Gly Ala Asn Tyr Cys Arg Phe145 150 155 160Gln Asn Phe Phe Pro Ile Thr Ala Val Phe Ala Ser Ile Tyr Ser Met
165 170 175Thr Ala Ile Ala Val Asp Arg Tyr Met Ala Ile Ile Asp Pro Leu Lys
180 185 190Pro Arg Leu Ser Ala Thr Ala Thr Lys Ile Val Ile Gly Ser Ile Trp
195 200 205Ile Leu Ala Phe Leu Leu Ala Phe Pro Gln Cys Leu Tyr Ser Lys Thr
210 215 220Lys Val Met Pro Gly Arg Thr Leu Cys Phe Val Gln Trp Pro Glu Gly225 230 235 240Pro Lys Gln His Phe Thr Tyr His Ile Ile Val Ile Ile Leu Val Tyr
245 250 255Cys Phe Pro Leu Leu Ile Met Gly Ile Thr Tyr Thr Ile Val Gly Ile
260 265 270Thr Leu Trp Gly Gly Glu Ile Pro Gly Asp Thr Cys Asp Lys Tyr His
275 280 285Glu Gln Leu Lys Ala Lys Arg Lys Val Lys Lys Met Met Ile Ile Val
290 295 300Val Met Thr Phe Ala Ile Cys Trp Leu Pro Tyr His Ile Tyr Phe Ile305 310 315 320Leu Thr Ala Ile Tyr Gln Gln Leu Asn Arg Trp Lys Tyr Ile Gln Gln
325 330 335Val Tyr Leu Ala Ser Phe Trp Leu Ala Met Ser Ser Thr Met Tyr Asn
340 345 350Pro Ile Ile Tyr Cys Cys Leu Asn Lys Arg Phe Arg Ala Gly Phe Lys
355 360 365Arg Ala Phe Arg Trp Cys Pro Phe Ile Lys Val Ser Ser Tyr Asp Glu
370 375 380Leu Glu Leu Lys Thr Thr Arg Phe His Pro Asn Arg Gln Ser Ser Met385 390 395 400Tyr Thr Val Thr Arg Met Glu Ser Met Thr Val Val Phe Asp Pro Asn
405 410 415Asp Ala Asp Thr Thr Arg Ser Ser Arg Lys Lys Arg Ala Thr Pro Arg
420 425 430Asp Pro Ser Phe Asn Gly Cys Ser Arg Arg Asn Ser Lys Ser Ala Ser
435 440 445Ala Thr Ser Ser Phe Ile Ser Ser Pro Tyr Thr Ser Val Asp Glu Tyr
450 455 460Ser465<210>530<211>1173<212>DNA<213>智人(Homo sapiens)<400>530atgccctcta agtctctttc caacctctcg gtgaccaccg gcgcgaatga gagcggttcc 60gttcccgagg ggtgggaaag ggatttcctg ccggcctcgg acgggaccac cacggagttg 120gtgatccgct gtgtgatccc gtccctctac ctgctcatca tcaccgtggg cttgctgggc 180aacatcatgc tggtgaagat cttcatcacc aacagcgcca tgaggagcgt ccccaacatc 240ttcatctcta acctggcggc cggggacttg ctgctgctgc tcacctgcgt cccggtggac 300gcctcgcgct acttcttcga cgagtggatg tttggcaagg tgggctgcaa actgatccct 360gtcatccagc tcacttccgt gggggtttcc gtgttcactc tcactgccct cagcgcegac 420aggtacagag ccatcgttaa ccccatggac atgcagacgt caggggcatt gctgcggacc 480tgtgtgaagg ccatgggtat ctgggtggtc tccgtgttgc tggcagttcc cgaagcggtg 540ttttcagaag tggctcgcat cagtagcttg gataatagca gcttcacagc atgtatccca 600taccctcaaa cagatgaatt acatccaaag attcattcag tgctcatttt cttggtctat 660ttcctcatac cacttgctat tattagcatt tattattatc atattgcaaa gaccttaatt 720aaaagcgcac acaatcttcc tggagaatac aatgaacata ccaaaaaaca gatggaaaca 780cggaaacgcc tgaaaaaaat tgtgcttgtc tttgtgggct gtttcatctt ctgttggttt 840ccaaaccaca tcctttacat gtatcggtct ttcaactata atgagattga tccatctcta 900ggccacatga ttgtcacctt agttgcccgg gttctcagtt ttggcaattc ttgtgtcaac 960ccatttgctc tttacctact cagtgaaagc ttcaggaggc atttcaacag ccaactctgc 1020tgtgggagga agtcctatca agagagagga accagctacc tactcagctc ttcagcggtg 1080cgtatgacat ctctgaaaag caatgctaag aacatggtga ccaattctgt tttactaaat 1140gggcacagca tgaagcagga aatggcaatg tga 1173<210>531<211>390<212>PRT<213>智人(Homo sapiens)<400>531Met Pro Ser Lys Ser Leu Ser Asn Leu Ser Val Thr Thr Gly Ala Asn1 5 10 15Glu Ser Gly Ser Val Pro Glu Gly Trp Glu Arg Asp Phe Leu Pro Ala
20 25 30Ser Asp Gly Thr Thr Thr Glu Leu Val Ile Arg Cys Val Ile Pro Ser
35 40 45Leu Tyr Leu Leu Ile Ile Thr Val Gly Leu Leu Gly Asn Ile Met Leu
50 55 60Val Lys Ile Phe Ile Thr Asn Ser Ala Met Arg Ser Val Pro Asn Ile65 70 75 80Phe Ile Ser Asn Leu Ala Ala Gly Asp Leu Leu Leu Leu Leu Thr Cys
85 90 95Val Pro Val Asp Ala Ser Arg Tyr Phe Phe Asp Glu Trp Met Phe Gly
100 105 110Lys Val Gly Cys Lys Leu Ile Pro Val Ile Gln Leu Thr Ser Val Gly
115 120 125Val Ser Val Phe Thr Leu Thr Ala Leu Ser Ala Asp Arg Tyr Arg Ala
130 135 140Ile Val Asn Pro Met Asp Met Gln Thr Ser Gly Ala Leu Leu Arg Thr145 150 155 160Cys Val Lys Ala Met Gly Ile Trp Val Val Ser Val Leu Leu Ala Val
165 170 175Pro Glu Ala Val Phe Ser Glu Val Ala Arg Ile Ser Ser Leu Asp Asn
180 185 190Ser Ser Phe Thr Ala Cys Ile Pro Tyr Pro Gln Thr Asp Glu Leu His
195 200 205Pro Lys Ile His Ser Val Leu Ile Phe Leu Val Tyr Phe Leu Ile Pro
210 215 220Leu Ala Ile Ile Ser Ile Tyr Tyr Tyr His Ile Ala Lys Thr Leu Ile225 230 235 240Lys Ser Ala His Asn Leu Pro Gly Glu Tyr Asn Glu His Thr Lys Lys
245 250 255Gln Met Glu Thr Arg Lys Arg Leu Lys Lys Ile Val Leu Val Phe Val
260 265 270Gly Cys Phe Ile Phe Cys Trp Phe Pro Asn His Ile Leu Tyr Met Tyr
275 280 285Arg Ser Phe Asn Tyr Asn Glu Ile Asp Pro Ser Leu Gly His Met Ile
290 295 300Val Thr Leu Val Ala Arg Val Leu Ser Phe Gly Asn Ser Cys Val Asn305 310 315 320Pro Phe Ala Leu Tyr Leu Leu Ser Glu Ser Phe Arg Arg His Phe Asn
325 330 335Ser Gln Leu Cys Cys Gly Arg Lys Ser Tyr Gln Glu Arg Gly Thr Ser
340 345 350Tyr Leu Leu Ser Ser Ser Ala Val Arg Met Thr Ser Leu Lys Ser Asn
355 360 365Ala Lys Asn Met Val Thr Asn Ser Val Leu Leu Asn Gly His Ser Met
370 375 380Lys Gln Glu Met Ala Met385 390<210>532<211>1338<212>DNA<213>智人(Homo sapiens)<400>532atggatttag agctcgacga gtattataac aagacacttg ccacagagaa taatactgct 60gccactcgga attctgattt cccagtctgg gatgactata aaagcagtgt agatgactta 120cagtattttc tgattgggct ctatacattt gtaagtcttc ttggctttat ggggaatcta 180cttattttaa tggctctcat gaaaaagcgt aatcagaaga ctacggtaaa cttcctcata 240ggcaatctgg ccttttctga tatcttggtt gtgctgtttt gctcaccttt cacactgacg 300tctgtcttgc tggatcagtg gatgtttggc aaagtcatgt gccatattat gccttttctt 360caatgtgtgt cagttttggt ttcaacttta attttaatat caattgccat tgtcaggtat 420catatgataa aacatcccat atctaataat ttaacagcaa accatggcta ctttctgata 480gctactgtct ggacactagg ttttgccatc tgttctcccc ttccagtgtt tcacagtctt 540gtggaacttc aagaaacatt tggttcagca ttgctgagca gcaggtattt atgtgttgag 600tcatggccat ctgattcata cagaattgcc tttactatct ctttattgct agttcagtat 660attctgccct tagtttgtct tactgtaagt catacaagtg tctgcagaag tataagctgt 720ggattgtcca acaaagaaaa cagacttgaa gaaaatgaga tgatcaactt aactcttcat 780ccatccaaaa agagtgggcc tcaggtgaaa ctctctggca gccataaatg gagttattca 840ttcatcaaaa aacacagaag aagatatagc aagaagacag catgtgtgtt acctgctcca 900gaaagacctt ctcaagagaa ccactccaga atacttccag aaaactttgg ctctgtaaga 960agtcagctct cttcatccag taagttcata ccaggggtcc ccacttgctt tgagataaaa 1020cctgaagaaa attcagatgt tcatgaattg agagtaaaac gttctgttac aagaataaaa 1080aagagatctc gaagtgttaa gtacagactg accatactga tattagtatt tgctgttagt 1140tggatgccac tacacctttt ccatgtggta actgatttta atgacaatct tatttcaaat 1200aggcatttca agttggtgta ttgcatttgt catttgttgg gcatgatgtc ctgttgtctt 1260aatccaattc tatatgggtt tcttaataat gggattaaag ctgatttagt gtcccttata 1320cactgtcttc atatgtaa 1338<210>533<211>445<212>PRT<213>智人(Homo sapiens)<400>533Met Asp Leu Glu Leu Asp Glu Tyr Tyr Asn Lys Thr Leu Ala Thr Glu1 5 10 15Asn Asn Thr Ala Ala Thr Arg Asn Ser Asp Phe Pro Val Trp Asp Asp
20 25 30Tyr Lys Ser Ser Val Asp Asp Leu Gln Tyr Phe Leu Ile Gly Leu Tyr
35 40 45Thr Phe Val Ser Leu Leu Gly Phe Met Gly Asn Leu Leu Ile Leu Met
50 55 60Ala Leu Met Lys Lys Arg Asn Gln Lys Thr Thr Val Asn Phe Leu Ile65 70 75 80Gly Asn Leu Ala Phe Ser Asp Ile Leu Val Val Leu Phe Cys Ser Pro
85 90 95Phe Thr Leu Thr Ser Val Leu Leu Asp Gln Trp Met Phe Gly Lys Val
100 105 110Met Cys His Ile Met Pro Phe Leu Gln Cys Val Ser Val Leu Val Ser
115 120 125Thr Leu Ile Leu Ile Ser Ile Ala Ile Val Arg Tyr His Met Ile Lys
130 135 140His Pro Ile Ser Asn Asn Leu Thr Ala Asn His Gly Tyr Phe Leu Ile145 150 155 160Ala Thr Val Trp Thr Leu Gly Phe Ala Ile Cys Ser Pro Leu Pro Val
165 170 175Phe His Ser Leu Val Glu Leu Gln Glu Thr Phe Gly Ser Ala Leu Leu
180 185 190Ser Ser Arg Tyr Leu Cys Val Glu Ser Trp Pro Ser Asp Ser Tyr Arg
195 200 205Ile Ala Phe Thr Ile Ser Leu Leu Leu Val Gln Tyr Ile Leu Pro Leu
210 215 220Val Cys Leu Thr Val Ser His Thr Ser Val Cys Arg Ser Ile Ser Cys225 230 235 240Gly Leu Ser Asn Lys Glu Asn Arg Leu Glu Glu Asn Glu Met Ile Asn
245 250 255Leu Thr Leu His Pro Ser Lys Lys Ser Gly Pro Gln Val Lys Leu Ser
260 265 270Gly Ser His Lys Trp Ser Tyr Ser Phe Ile Lys Lys His Arg Arg Arg
275 280 285Tyr Ser Lys Lys Thr Ala Cys Val Leu Pro Ala Pro Glu Arg Pro Ser
290 295 300Gln Glu Asn His Ser Arg Ile Leu Pro Glu Asn Phe Gly Ser Val Arg305 310 315 320Ser Gln Leu Ser Ser Ser Ser Lys Phe Ile Pro Gly Val Pro Thr Cys
325 330 335Phe Glu Ile Lys Pro Glu Glu Asn Ser Asp Val His Glu Leu Arg Val
340 345 350Lys Arg Ser Val Thr Arg Ile Lys Lys Arg Ser Arg Ser Val Lys Tyr
355 360 365Arg Leu Thr Ile Leu Ile Leu Val Phe Ala Val Ser Trp Met Pro Leu
370 375 380His Leu Phe His Val Val Thr Asp Phe Asn Asp Asn Leu Ile Ser Asn385 390 395 400Arg His Phe Lys Leu Val Tyr Cys Ile Cys His Leu Leu Gly Met Met
405 410 415Ser Cys Cys Leu Asn Pro Ile Leu Tyr Gly Phe Leu Asn Asn Gly Ile
420 425 430Lys Ala Asp Leu Val Ser Leu Ile His Cys Leu His Met
435 440 445<210>534<211>1257<212>DNA<213>智人(Homo sapiens)<400>534atgcgcctca acagctccgc gccgggaacc ccgggcacgc cggccgccga ccccttccag 60cgggcgcagg ccggactgga ggaggcgctg ctggccccgg gcttcggcaa cgcttcgggc 120aacgcgtcgg agcgcgtcct ggcggcaccc agcagcgagc tggacgtgaa caccgacatc 180tactccaaag tgctggtgac cgccgtgtac ctggcgctct tcgtggtggg cacggtgggc 240aacacggtga cggcgttcac gctggcgcgg aagaagtcgc tgcagagcct gcagagcacg 300gtgcattacc acctgggcag cctggcgctg tccgacctgc tcaccctgct gctggccatg 360cccgtggagc tgtacaactt catctgggtg caccacccct gggccttcgg cgacgccggc 420tgccgcggct actacttcct gcgcgacgcc tgcacctacg ccacggccct caacgtggcc 480agcctgagtg tggagcgcta cctggccatc tgccacccct tcaaggccaa gaccctcatg 540tcccgaagcc gcaccaagaa gttcatcagc gccatctggc tcgcctcggc cctgctgacg 600gtgcctatgc tgttcaccat gggcgagcag aaccgcagcg ccgacggcca gcacgccggc 660ggcctggtgt gcacccccac catccacact gccaccgtca aggtcgtcat acaggtcaac 720accttcatgt ccttcatatt ccccatggtg gtcatctcgg tcctgaacac catcatcgcc 780aacaagctga ccgtcatggt acgccaggcg gccgagcagg gccaagtgtg cacggtcggg 840ggcgagcaca gcacattcag catggccatc gagcctggca gggtccaggc cctgcggcac 900ggcaagcgcg tcctacgtgc agtggtcatc gcctttgtgg tctgctggct gccctaccac 960gtgcggcgcc tcatgttctg ctacatctcg gatgagcagt ggactccgtt cctctatgac 1020ttctaccact acttctacat ggtgaccaac gcactcttct acgtcagctc caccatcaac 1080cccatcctgt acaacctcgt ctctgccaac ttccgccaca tcttcctggc cacactggcc 1140tgcctctgcc cggtgtggcg gcgcaggagg aagaggccag ccttctcgag gaaggccgac 1200agcgtgtcca gcaaccacac cctctccagc aatgccaccc gcgagacgct gtactag 1257<210>535<211>418<212>PRT<213>智人(Homo sapiens)<400>535Met Arg Leu Asn Ser Ser Ala Pro Gly Thr Pro Gly Thr Pro Ala Ala1 5 10 15Asp Pro Phe Gln Arg Ala Gln Ala Gly Leu Glu Glu Ala Leu Leu Ala
20 25 30Pro Gly Phe Gly Asn Ala Ser Gly Asn Ala Ser Glu Arg Val Leu Ala
35 40 45Ala Pro Ser Ser Glu Leu Asp Val Asn Thr Asp Ile Tyr Ser Lys Val
50 55 60Leu Val Thr Ala Val Tyr Leu Ala Leu Phe Val Val Gly Thr Val Gly65 70 75 80Asn Thr Val Thr Ala Phe Thr Leu Ala Arg Lys Lys Ser Leu Gln Ser
85 90 95Leu Gln Ser Thr Val His Tyr His Leu Gly Ser Leu Ala Leu Ser Asp
100 105 110Leu Leu Thr Leu Leu Leu Ala Met Pro Val Glu Leu Tyr Asn Phe Ile
115 120 125Trp Val His His Pro Trp Ala Phe Gly Asp Ala Gly Cys Arg Gly Tyr
130 135 140Tyr Phe Leu Arg Asp Ala Cys Thr Tyr Ala Thr Ala Leu Asn Val Ala145 150 155 160Ser Leu Ser Val Glu Arg Tyr Leu Ala Ile Cys His Pro Phe Lys Ala
165 170 175Lys Thr Leu Met Ser Arg Ser Arg Thr Lys Lys Phe Ile Ser Ala Ile
180 185 190Trp Leu Ala Ser Ala Leu Leu Thr Val Pro Met Leu Phe Thr Met Gly
195 200 205Glu Gln Asn Arg Ser Ala Asp Gly Gln His Ala Gly Gly Leu Val Cys
210 215 220Thr Pro Thr Ile His Thr Ala Thr Val Lys Val Val Ile Gln Val Asn225 230 235 240Thr Phe Met Ser Phe Ile Phe Pro Met Val Val Ile Ser Val Leu Asn
245 250 255Thr Ile Ile Ala Asn Lys Leu Thr Val Met Val Arg Gln Ala Ala Glu
260 265 270Gln Gly Gln Val Cys Thr Val Gly Gly Glu His Ser Thr Phe Ser Met
275 280 285Ala Ile Glu Pro Gly Arg Val Gln Ala Leu Arg His Gly Lys Arg Val
290 295 300Leu Arg Ala Val Val Ile Ala Phe Val Val Cys Trp Leu Pro Tyr His305 310 315 320Val Arg Arg Leu Met Phe Cys Tyr Ile Ser Asp Glu Gln Trp Thr Pro
325 330 335Phe Leu Tyr Asp Phe Tyr His Tyr Phe Tyr Met Val Thr Asn Ala Leu
340 345 350Phe Tyr Val Ser Ser Thr Ile Asn Pro Ile Leu Tyr Asn Leu Val Ser
355 360 365Ala Asn Phe Arg His Ile Phe Leu Ala Thr Leu Ala Cys Leu Cys Pro
370 375 380Val Trp Arg Arg Arg Arg Lys Arg Pro Ala Phe Ser Arg Lys Ala Asp385 390 395 400Ser Val Ser Ser Asn His Thr Leu Ser Ser Asn Ala Thr Arg Glu Thr
405 410 415Leu Tyr<210>536<211>1233<212>DNA<213>智人(Homo sapiens)<400>536atggaaacca gcagcccgcg gcccccgcgg cccagctcca acccggggct gagcctggac 60gcccggctgg gcgtggacac tcgcctctgg gccaaggtgc tgttcaccgc gctctacgca 120ctcatctggg cgctgggcgc ggcgggcaat gcgctgtccg tgcacgtggt gctgaaggcg 180cgggccgggc gcgcggggcg cctgcgccac cacgtgctca gcctggcgct cgcgggcctg 240ctgctgctgc tggtcggcgt gccggtggag ctctacagct tcgtgtggtt ccactacccc 300tgggtcttcg gcgacctggg ctgccgcggc tactacttcg tgcacgagct gtgcgcctac 360gccacggtgc tgagcgtggc aggcctgagc gccgagcgct gcctagccgt gtgccagccc 420ctgcgtgccc gcagcctgct gacgccacgc cggacccggt ggctggtggc gctctcgtgg 480gccgcctcgc tcggcctcgc cctgcccatg gccgtcatca tggggcagaa gcacgaactc 540gagacggcgg acggggagcc ggagcccgcc tcgcgagtgt gcacggtgct ggtgagccgc 600accgcgctcc aagtctttat ccaggtgaat gtgctggtgt ccttcgtgct ccccttggca 660ctaactgctt tcctgaatgg ggtcacagtg agccacctgc tggccctctg ctcccaagtg 720ccgtccactt ctaccccggg cagctccacc cccagccgcc tggagctgct gagtgaggag 780ggtctcctca gcttcatcgt atggaagaag acctttatcc agggaggcca ggtcagcctg 840gtgagacata aagacgtgcg ccggatccgc agcctccagc gcagcaagca ggttctcaga 900gccatcgtgg tcatgtatgt catctgctgg ctgccgtacc atgcccgcag gctcatgtac 960tgctacgtac ctgatgacgc gtggactgac ccactgtaca atttctacca ctacttctac 1020atggtgacca acacactttt ctacgtcagc tcagctgtga ctcctcttct ctacaacgcc 1080gtgtcctcct ccttcagaaa actcttcctg gaagccgtca gctccctgtg tggagagcac 1140caccccatga agcggttacc cccgaagccc cagagtccca ccctaatgga tacagcttca 1200ggctttgggg atcccccaga aacccggacc tga 1233<210>537<211>410<212>PRT<213>智人(Homo sapiens)<400>537Met Glu Thr Ser Ser Pro Arg Pro Pro Arg Pro Ser Ser Asn Pro Gly1 5 10 15Leu Ser Leu Asp Ala Arg Leu Gly Val Asp Thr Arg Leu Trp Ala Lys
20 25 30Val Leu Phe Thr Ala Leu Tyr Ala Leu Ile Trp Ala Leu Gly Ala Ala
35 40 45Gly Asn Ala Leu Ser Val His Val Val Leu Lys Ala Arg Ala Gly Arg
50 55 60Ala Gly Arg Leu Arg His His Val Leu Ser Leu Ala Leu Ala Gly Leu65 70 75 80Leu Leu Leu Leu Val Gly Val Pro Val Glu Leu Tyr Ser Phe Val Trp
85 90 95Phe His Tyr Pro Trp Val Phe Gly Asp Leu Gly Cys Arg Gly Tyr Tyr
100 105 110Phe Val His Glu Leu Cys Ala Tyr Ala Thr Val Leu Ser Val Ala Gly
115 120 125Leu Ser Ala Glu Arg Cys Leu Ala Val Cys Gln Pro Leu Arg Ala Arg
130 135 140Ser Leu Leu Thr Pro Arg Arg Thr Arg Trp Leu Val Ala Leu Ser Trp145 150 155 160Ala Ala Ser Leu Gly Leu Ala Leu Pro Met Ala Val Ile Met Gly Gln
165 170 175Lys His Glu Leu Glu Thr Ala Asp Gly Glu Pro Glu Pro Ala Ser Arg
180 185 190Val Cys Thr Val Leu Val Ser Arg Thr Ala Leu Gln Val Phe Ile Gln
195 200 205Val Asn Val Leu Val Ser Phe Val Leu Pro Leu Ala Leu Thr Ala Phe
210 215 220Leu Asn Gly Val Thr Val Ser His Leu Leu Ala Leu Cys Ser Gln Val225 230 235 240Pro Ser Thr Ser Thr Pro Gly Ser Ser Thr Pro Ser Arg Leu Glu Leu
245 250 255Leu Ser Glu Glu Gly Leu Leu Ser Phe Ile Val Trp Lys Lys Thr Phe
260 265 270Ile Gln Gly Gly Gln Val Ser Leu Val Arg His Lys Asp Val Arg Arg
275 280 285Ile Arg Ser Leu Gln Arg Ser Lys Gln Val Leu Arg Ala Ile Val Val
290 295 300Met Tyr Val Ile Cys Trp Leu Pro Tyr His Ala Arg Arg Leu Met Tyr305 310 315 320Cys Tyr Val Pro Asp Asp Ala Trp Thr Asp Pro Leu Tyr Asn Phe Tyr
325 330 335His Tyr Phe Tyr Met Val Thr Asn Thr Leu Phe Tyr Val Ser Ser Ala
340 345 350Val Thr Pro Leu Leu Tyr Asn Ala Val Ser Ser Ser Phe Arg Lys Leu
355 360 365Phe Leu Glu Ala Val Ser Ser Leu Cys Gly Glu His His Pro Met Lys
370 375 380Arg Leu Pro Pro Lys Pro Gln Ser Pro Thr Leu Met Asp Thr Ala Ser385 390 395 400Gly Phe Gly Asp Pro Pro Glu Thr Arg Thr
405 410<210>538<211>1119<212>DNA<213>智人(Homo sapiens)<400>538atggaaccgg ccccctccgc cggcgccgag ctgcagcccc cgctcttcgc caacgcctcg 60gacgcctacc ctagcgcctt ccccagcgct ggcgccaatg cgtcggggcc gccaggaccg 120gggagcgcct cgtccctcgc cctggcaatc gccatcaccg cgctctactc ggccgtgtgc 180gccgtggggc tgctgggcaa cgtgcttgtc atgttcggca tcgtccggta cactaagatg 240aagacggcca ccaacatcta catcttcaac ctggccttag ccgatgcgct ggccaccagc 300acgctgcctt tccagagtgc caagtacctg atggagacgt ggcccttcgg cgagctgctc 360tgcaaggctg tgctctccat cgactactac aatatgttca ccagcatctt cacgctcacc 420atgatgagtg ttgaccgcta catcgctgtc tgccaccctg tcaaggccct ggacttccgc 480acgcctgcca aggccaagct gatcaacatc tgtatctggg tcctggcctc aggcgttggc 540gtgcccatca tggtcatggc tgtgacccgt ccccgggacg gtgcagtggt gtgcatgctc 600cagttcccca gccccagctg gtactgggac acggtgacca agatctgcgt gttcctcttc 660gccttcgtgg tgcccatcct catcatcacc gtgtgctatg gcctcatgct gctgcgcctg 720cgcagtgtgc gcctgctgtc gggctccaag gagaaggacc gcagcctgcg gcgcatcaag 780cgcatggtgc tggtggttgt gggcgccttc gtggtgtgtt gggcgcccat ccacatcttc 840gtcatcgtct ggacgctggt ggacatcgac cggcgcgacc cgctggtggt ggctgcgctg 900cacctgtgca tcgcgctggg ctacgccaat agcagcctca accccgtgct ctacgctttc 960ctcgacgaga acttcaagcg ctgcttcegc cagctctgcc gcaagcectg cggcegccca 1020gaccccagca gcttcagccg gccccgcgaa gccacggccc gcgagcgtgt caccgcctgc 1080accccgtccg atggtcccgg cggtggccgt gccgcctga 1119<210>539<211>372<212>PRT<213>智人(Homo sapiens)<400>539Met Glu Pro Ala Pro Ser Ala Gly Ala Glu Leu Gln Pro Pro Leu Phe1 5 10 15Ala Asn Ala Ser Asp Ala Tyr Pro Ser Ala Phe Pro Ser Ala Gly Ala
20 25 30Asn Ala Ser Gly Pro Pro Gly Pro Gly Ser Ala Ser Ser Leu Ala Leu
35 40 45Ala Ile Ala Ile Thr Ala Leu Tyr Ser Ala Val Cys Ala Val Gly Leu
50 55 60Leu Gly Asn Val Leu Val Met Phe Gly Ile Val Arg Tyr Thr Lys Met65 70 75 80Lys Thr Ala Thr Asn Ile Tyr Ile Phe Asn Leu Ala Leu Ala Asp Ala
85 90 95Leu Ala Thr Ser Thr Leu Pro Phe Gln Ser Ala Lys Tyr Leu Met Glu
100 105 110Thr Trp Pro Phe Gly Glu Leu Leu Cys Lys Ala Val Leu Ser Ile Asp
115 120 125Tyr Tyr Asn Met Phe Thr Ser Ile Phe Thr Leu Thr Met Met Ser Val
130 135 140Asp Arg Tyr Ile Ala Val Cys His Pro Val Lys Ala Leu Asp Phe Arg145 150 155 160Thr Pro Ala Lys Ala Lys Leu Ile Asn Ile Cys Ile Trp Val Leu Ala
165 170 175Ser Gly Val Gly Val Pro Ile Met Val Met Ala Val Thr Arg Pro Arg
180 185 190Asp Gly Ala Val Val Cys Met Leu Gln Phe Pro Ser Pro Ser Trp Tyr
195 200 205Trp Asp Thr Val Thr Lys Ile Cys Val Phe Leu Phe Ala Phe Val Val
210 215 220Pro Ile Leu Ile Ile Thr Val Cys Tyr Gly Leu Met Leu Leu Arg Leu225 230 235 240Arg Ser Val Arg Leu Leu Ser Gly Ser Lys Glu Lys Asp Arg Ser Leu
245 250 255Arg Arg Ile Lys Arg Met Val Leu Val Val Val Gly Ala Phe Val Val
260 265 270Cys Trp Ala Pro Ile His Ile Phe Val Ile Val Trp Thr Leu Val Asp
275 280 285Ile Asp Arg Arg Asp Pro Leu Val Val Ala Ala Leu His Leu Cys Ile
290 295 300Ala Leu Gly Tyr Ala Asn Ser Ser Leu Asn Pro Val Leu Tyr Ala Phe305 310 315 320Leu Asp Glu Asn Phe Lys Arg Cys Phe Arg Gln Leu Cys Arg Lys Pro
325 330 335Cys Gly Arg Pro Asp Pro Ser Ser Phe Ser Arg Pro Arg Glu Ala Thr
340 345 350Ala Arg Glu Arg Val Thr Ala Cys Thr Pro Ser Asp Gly Pro Gly Gly
355 360 365Gly Arg Ala Ala
370<210>540<211>1113<212>DNA<213>智人(Homo sapiens)<400>540atggagcccc tcttccccgc gccgttctgg gaggttatct acggcagcca ccttcagggc 60aacctgtccc tcctgagccc caaccacagt ctgctgcccc cgcatctgct gctcaatgcc 120agccacggcg ccttcctgcc cctcgggctc aaggtcacca tcgtggggct ctacctggcc 180gtgtgtgtcg gagggctcct ggggaactgc cttgtcatgt acgtcatcct caggcacacc 240aaaatgaaga cagccaccaa tatttacatc tttaacctgg ccctggccga cactctggtc 300ctgctgacgc tgcccttcca gggcacggac atcctcctgg gcttctggcc gtttgggaat 360gcgctgtgca agacagtcat tgccattgac tactacaaca tgttcaccag caccttcacc 420ctaactgcca tgagtgtgga tcgctatgta gccatctgcc accccatccg tgccctcgac 480gtccgcacgt ccagcaaagc ccaggctgtc aatgtggcca tctgggccct ggcctctgtt 540gtcggtgttc ccgttgccat catgggctcg gcacaggtcg aggatgaaga gatcgagtgc 600ctggtggaga tccctacccc tcaggattac tggggcccgg tgtttgccat ctgcatcttc 660ctcttctcct tcatcgtccc cgtgctcgtc atctctgtct gctacagcct catgatccgg 720cggctccgtg gagtccgcct gctctcgggc tcccgagaga aggaccggaa cctgcggcgc 780atcaagcggc tggtgctggt ggtagtggct gtgttcgtgg gctgctggac gcctgtccag 840gtcttcgtgc tggcccaagg gctgggggtt cagccgagca gcgagactgc cgtggccatt 900ctgcgcttct gcacggccct gggctacgtc aacagctgcc tcaaccccat cctctacgcc 960ttcctggatg agaacttcaa ggcctgcttc cgcaagttct gctgtgcatc tgccctgcgc 1020cgggacgtgc aggtgtctga ccgcgtgcgc agcattgcca aggacgtggc cctggcctgc 1080aagacctctg agacggtacc gcggcccgca tga 1113<210>541<211>370<212>PRT<213>智人(Homo sapiens)<400>541Met Glu Pro Leu Phe Pro Ala Pro Phe Trp Glu Val Ile Tyr Gly Ser1 5 10 15His Leu Gln Gly Asn Leu Ser Leu Leu Ser Pro Asn His Ser Leu Leu
20 25 30Pro Pro His Leu Leu Leu Asn Ala Ser His Gly Ala Phe Leu Pro Leu
35 40 45Gly Leu Lys Val Thr Ile Val Gly Leu Tyr Leu Ala Val Cys Val Gly
50 55 60Gly Leu Leu Gly Asn Cys Leu Val Met Tyr Val Ile Leu Arg His Thr65 70 75 80Lys Met Lys Thr Ala Thr Asn Ile Tyr Ile Phe Asn Leu Ala Leu Ala
85 90 95Asp Thr Leu Val Leu Leu Thr Leu Pro Phe Gln Gly Thr Asp Ile Leu
100 105 110Leu Gly Phe Trp Pro Phe Gly Asn Ala Leu Cys Lys Thr Val Ile Ala
115 120 125Ile Asp Tyr Tyr Asn Met Phe Thr Ser Thr Phe Thr Leu Thr Ala Met
130 135 140Ser Val Asp Arg Tyr Val Ala Ile Cys His Pro Ile Arg Ala Leu Asp145 150 155 160Val Arg Thr Ser Ser Lys Ala Gln Ala Val Asn Val Ala Ile Trp Ala
165 170 175Leu Ala Ser Val Val Gly Val Pro Val Ala Ile Met Gly Ser Ala Gln
180 185 190Val Glu Asp Glu Glu Ile Glu Cys Leu Val Glu Ile Pro Thr Pro Gln
195 200 205Asp Tyr Trp Gly Pro Val Phe Ala Ile Cys Ile Phe Leu Phe Ser Phe
210 215 220Ile Val Pro Val Leu Val Ile Ser Val Cys Tyr Ser Leu Met Ile Arg225 230 235 240Arg Leu Arg Gly Val Arg Leu Leu Ser Gly Ser Arg Glu Lys Asp Arg
245 250 255Asn Leu Arg Arg Ile Lys Arg Leu Val Leu Val Val Val Ala Val Phe
260 265 270Val Gly Cys Trp Thr Pro Val Gln Val Phe Val Leu Ala Gln Gly Leu
275 280 285Gly Val Gln Pro Ser Ser Glu Thr Ala Val Ala Ile Leu Arg Phe Cys
290 295 300Thr Ala Leu Gly Tyr Val Asn Ser Cys Leu Asn Pro Ile Leu Tyr Ala305 310 315 320Phe Leu Asp Glu Asn Phe Lys Ala Cys Phe Arg Lys Phe Cys Cys Ala
325 330 335Ser Ala Leu Arg Arg Asp Val Gln Val Ser Asp Arg Val Arg Ser Ile
340 345 350Ala Lys Asp Val Ala Leu Ala Cys Lys Thr Ser Glu Thr Val Pro Arg
355 360 365Pro Ala
370<210>542<211>1143<212>DNA<213>智人(Homo sapiens)<400>542atggaatccc cgattcagat cttccgcggg gagcctggcc ctacctgcgc cccgagcgcc 60tgcctgcccc ccaacagcag cgcctggttt cccggctggg ccgagcccga cagcaacggc 120agcgccggct cggaggacgc gcagctggag cccgcgcaca tctccccggc catcccggtc 180atcatcacgg cggtctactc cgtagtgttc gtcgtgggct tggtgggcaa ctcgctggtc 240atgttcgtga tcatccgata cacaaagatg aagacagcaa ccaacattta catatttaac 300ctggctttgg cagatgcttt agttactaca accatgccct ttcagagtac ggtctacttg 360atgaattcct ggccttttgg ggatgtgctg tgcaagatag taatttccat tgattactac 420aacatgttca ccagcatctt caccttgacc atgatgagcg tggaccgcta cattgccgtg 480tgccaccccg tgaaggcttt ggacttccgc acacccttga aggcaaagat catcaatatc 540tgcatctggc tgctgtcgtc atctgttggc atctctgcaa tagtccttgg aggcaccaaa 600gtcagggaag acgtcgatgt cattgagtgc tccttgcagt tcccagatga tgactactcc 660tggtgggacc tcttcatgaa gatctgcgtc ttcatctttg ccttcgtgat ccctgtcctc 720atcatcatcg tctgctacac cctgatgatc ctgcgtctca agagcgtccg gctcctttct 780ggctcccgag agaaagatcg caacctgcgt aggatcaaga gactggtcct ggtggtggtg 840gcggttttcg tcgtctgctg gactcccatt cacatattca tcctggtgga ggctctgggg 900agcacctccc acagcacagc tgctctctcc agctattact tctgcatcgc cttaggctat 960accaacagta gcctgaatcc cattctctac gcctttcttg atgaaaactt caagcggtgt 1020ttccgggact tctgctttcc actgaagatg aggatggagc ggcagagcac tagcagagtc 1080cgaaatacag ttcaggatcc tgcttacctg agggacatcg atgggatgaa taaaccagta 1140tga 1143<210>543<211>380<212>PRT<213>智人(Homo sapiens)<400>543Met Glu Ser Pro Ile Gln Ile Phe Arg Gly Glu Pro Gly Pro Thr Cys1 5 10 15Ala Pro Ser Ala Cys Leu Pro Pro Asn Ser Ser Ala Trp Phe Pro Gly
20 25 30Trp Ala Glu Pro Asp Ser Asn Gly Ser Ala Gly Ser Glu Asp Ala Gln
35 40 45Leu Glu Pro Ala His Ile Ser Pro Ala Ile Pro Val Ile Ile Thr Ala
50 55 60Val Tyr Ser Val Val Phe Val Val Gly Leu Val Gly Asn Ser Leu Val65 70 75 80Met Phe Val Ile Ile Arg Tyr Thr Lys Met Lys Thr Ala Thr Asn Ile
85 90 95Tyr Ile Phe Asn Leu Ala Leu Ala Asp Ala Leu Val Thr Thr Thr Met
100 105 110Pro Phe Gln Ser Thr Val Tyr Leu Met Asn Ser Trp Pro Phe Gly Asp
115 120 125Val Leu Cys Lys Ile Val Ile Ser Ile Asp Tyr Tyr Asn Met Phe Thr
130 135 140Ser Ile Phe Thr Leu Thr Met Met Ser Val Asp Arg Tyr Ile Ala Val145 150 155 160Cys His Pro Val Lys Ala Leu Asp Phe Arg Thr Pro Leu Lys Ala Lys
165 170 175Ile Ile Asn Ile Cys Ile Trp Leu Leu Ser Ser Ser Val Gly Ile Ser
180 185 190Ala Ile Val Leu Gly Gly Thr Lys Val Arg Glu Asp Val Asp Val Ile
195 200 205Glu Cys Ser Leu Gln Phe Pro Asp Asp Asp Tyr Ser Trp Trp Asp Leu
210 215 220Phe Met Lys Ile Cys Val Phe Ile Phe Ala Phe Val Ile Pro Val Leu225 230 235 240Ile Ile Ile Val Cys Tyr Thr Leu Met Ile Leu Arg Leu Lys Ser Val
245 250 255Arg Leu Leu Ser Gly Ser Arg Glu Lys Asp Arg Asn Leu Arg Arg Ile
260 265 270Lys Arg Leu Val Leu Val Val Val Ala Val Phe Val Val Cys Trp Thr
275 280 285Pro Ile His Ile Phe Ile Leu Val Glu Ala Leu Gly Ser Thr Ser His
290 295 300Ser Thr Ala Ala Leu Ser Ser Tyr Tyr Phe Cys Ile Ala Leu Gly Tyr305 310 315 320Thr Asn Ser Ser Leu Asn Pro Ile Leu Tyr Ala Phe Leu Asp Glu Asn
325 330 335Phe Lys Arg Cys Phe Arg Asp Phe Cys Phe Pro Leu Lys Met Arg Met
340 345 350Glu Arg Gln Ser Thr Ser Arg Val Arg Asn Thr Val Gln Asp Pro Ala
355 360 365Tyr Leu Arg Asp Ile Asp Gly Met Asn Lys Pro Val
370 375 380<210>544<211>1203<212>DNA<213>智人(Homo sapiens)<400>544atggacagca gcgctgcccc cacgaacgcc agcaattgca ctgatgcctt ggcgtactca 60agttgctccc cagcacccag ccccggttcc tgggtcaact tgtcccactt agatggcaac 120ctgtccgacc catgcggtcc gaaccgcacc aacctgggcg ggagagacag cctgtgccct 180ccgaccggca gtccctccat gatcacggcc atcacgatca tggccctcta ctccatcgtg 240tgcgtggtgg ggctcttcgg aaacttcctg gtcatgtatg tgattgtcag atacaccaag 300atgaagactg ccaccaacat ctacattttc aaccttgctc tggcagatgc cttagccacc 360agtaccctgc ccttccagag tgtgaattac ctaatgggaa catggccatt tggaaccatc 420ctttgcaaga tagtgatctc catagattac tataacatgt tcaccagcat attcaccctc 480tgcaccatga gtgttgatcg atacattgca gtctgccacc ctgtcaaggc cttagatttc 540cgtactcccc gaaatgccaa aattatcaat gtctgcaact ggatcctctc ttcagccatt 600ggtcttcctg taatgttcat ggctacaaca aaatacaggc aaggttccat agattgtaca 660ctaacattct ctcatccaac ctggtactgg gaaaacctcg tgaagatctg tgttttcatc 720ttcgccttca ttatgccagt gctcatcatt accgtgtgct atggactgat gatcttgcgc 780ctcaagagtg tccgcatgct ctctggctcc aaagaaaagg acaggaatct tcgaaggatc 840aagaggatgg tgctggtggt ggtggctgtg ttcatcgtct gctggactcc cattcacatt 900tacgtcatca ttaaagcctt ggttacaatc ccagaaacta cgttccagac tgtttcttgg 960cacttctgca ttgctctagg ttacacaaac agctgcctca acccagtcct ttatgcattt 1020ctggatgaaa acttcaaacg atgcttcaga gagttctgta tcccaacctc ttccaacatt 1080gagcaacaaa actccactcg aattcgtcag aacactagag accacccctc cacggccaat 1140acagtggata gaactaatca tcagctagaa aatctggaag cagaaactgc tccgttgccc 1200taa 1203<210>545<211>400<212>PRT<213>智人(Homo sapiens)<400>545Met Asp Ser Ser Ala Ala Pro Thr Asn Ala Ser Asn Cys Thr Asp Ala1 5 10 15Leu Ala Tyr Ser Ser Cys Ser Pro Ala Pro Ser Pro Gly Ser Trp Val
20 25 30Asn Leu Ser His Leu Asp Gly Asn Leu Ser Asp Pro Cys Gly Pro Asn
35 40 45Arg Thr Asn Leu Gly Gly Arg Asp Ser Leu Cys Pro Pro Thr Gly Ser
50 55 60Pro Ser Met Ile Thr Ala Ile Thr Ile Met Ala Leu Tyr Ser Ile Val65 70 75 80Cys Val Val Gly Leu Phe Gly Asn Phe Leu Val Met Tyr Val Ile Val
85 90 95Arg Tyr Thr Lys Met Lys Thr Ala Thr Asn Ile Tyr Ile Phe Asn Leu
100 105 110Ala Leu Ala Asp Ala Leu Ala Thr Ser Thr Leu Pro Phe Gln Ser Val
115 120 125Asn Tyr Leu Met Gly Thr Trp Pro Phe Gly Thr Ile Leu Cys Lys Ile
130 135 140Val Ile Ser Ile Asp Tyr Tyr Asn Met Phe Thr Ser Ile Phe Thr Leu145 150 155 160Cys Thr Met Ser Val Asp Arg Tyr Ile Ala Val Cys His Pro Val Lys
165 170 175Ala Leu Asp Phe Arg Thr Pro Arg Asn Ala Lys Ile Ile Asn Val Cys
180 185 190Asn Trp Ile Leu Ser Ser Ala Ile Gly Leu Pro Val Met Phe Met Ala
195 200 205Thr Thr Lys Tyr Arg Gln Gly Ser Ile Asp Cys Thr Leu Thr Phe Ser
210 215 220His Pro Thr Trp Tyr Trp Glu Asn Leu Val Lys Ile Cys Val Phe Ile225 230 235 240Phe Ala Phe Ile Met Pro Val Leu Ile Ile Thr Val Cys Tyr Gly Leu
245 250 255Met Ile Leu Arg Leu Lys Ser Val Arg Met Leu Ser Gly Ser Lys Glu
260 265 270Lys Asp Arg Asn Leu Arg Arg Ile Lys Arg Met Val Leu Val Val Val
275 280 285Ala Val Phe Ile Val Cys Trp Thr Pro Ile His Ile Tyr Val Ile Ile
290 295 300Lys Ala Leu Val Thr Ile Pro Glu Thr Thr Phe Gln Thr Val Ser Trp305 310 315 320His Phe Cys Ile Ala Leu Gly Tyr Thr Asn Ser Cys Leu Asn Pro Val
325 330 335Leu Tyr Ala Phe Leu Asp Glu Asn Phe Lys Arg Cys Phe Arg Glu Phe
340 345 350Cys Ile Pro Thr Ser Ser Asn Ile Glu Gln Gln Asn Ser Thr Arg Ile
355 360 365Arg Gln Asn Thr Arg Asp His Pro Ser Thr Ala Asn Thr Val Asp Arg
370 375 380Thr Asn His Gln Leu Glu Asn Leu Glu Ala Glu Thr Ala Pro Leu Pro385 390 395 400<210>546<211>1182<212>DNA<213>智人(Homo sapiens)<400>546atggacagca gcgctgcccc cacgaacgcc agcaattgca ctgatgcctt ggcgtactca 60agttgctccc cagcacccag ccccggttcc tgggtcaact tgtcccactt agatggcaac 120ctgtccgacc catgcggtcc gaaccgcacc aacctgggcg ggagagacag cctgtgccct 180ccgaccggca gtccctccat gatcacggcc atcacgatca tggccctcta ctccatcgtg 240tgcgtggtgg ggctcttcgg aaacttcctg gtcatgtatg tgattgtcag atacaccaag 300atgaagactg ccaccaacat ctacattttc aaccttgctc tggcagatgc cttagccacc 360agtaccctgc ccttccagag tgtgaattac ctaatgggaa catggccatt tggaaccatc 420ctttgcaaga tagtgatctc catagattac tataacatgt tcaccagcat attcaccctc 480tgcaccatga gtgttgatcg atacattgca gtctgccacc ctgtcaaggc cttagatttc 540cgtactcccc gaaatgccaa aattatcaat gtctgcaact ggatcctctc ttcagccatt 600ggtcttcctg taatgttcat ggctacaaca aaatacaggc aaggttccat agattgtaca 660ctaacattct ctcatccaac ctggtactgg gaaaacctcg tgaagatctg tgttttcatc 720ttcgccttca ttatgccagt gctcatcatt accgtgtgct atggactgat gatcttgcgc 780ctcaagagtg tccgcatgct ctctggctcc aaagaaaagg acaggaatct tcgaaggatc 840aagaggatgg tgctggtggt ggtggctgtg ttcatcgtct gctggactcc cattcacatt 900tacgtcatca ttaaagcctt ggttacaatc ccagaaacta cgttccagac tgtttcttgg 960cacttctgca ttgctctagg ttacacaaac agctgcctca acccagtcct ttatgcattt 1020ctggatgaaa acttcaaacg atgcttcaga gagttctgta tcccaacctc ttccaacatt 1080gagcaacaaa actccactcg aattcgtcag aacactagag accacccctc cacggccaat 1140acagtggata gaactaatca tcagctagta cgcagtctct ag 1182<210>547<211>392<212>PRT<213>智人(Homo sapiens)<400>547Met Asp Ser Ser Ala Ala Pro Thr Asn Ala Ser Asn Cys Thr Asp Ala1 5 10 15Leu Ala Tyr Ser Ser Cys Ser Pro Ala Pro Ser Pro Gly Ser Trp Val
20 25 30Asn Leu Ser His Leu Asp Gly Asn Leu Ser Asp Pro Cys Gly Pro Asn
35 40 45Arg Thr Asn Leu Gly Gly Arg Asp Ser Leu Cys Pro Pro Thr Gly Ser
50 55 60Pro Ser Met Ile Thr Ala Ile Thr Ile Met Ala Leu Tyr Ser Ile Val65 70 75 80Cys Val Val Gly Leu Phe Gly Asn Phe Leu Val Met Tyr Val Ile Val
85 90 95Arg Tyr Thr Lys Met Lys Thr Ala Thr Asn Ile Tyr Ile Phe Asn Leu
100 105 110Ala Leu Ala Asp Ala Leu Ala Thr Ser Thr Leu Pro Phe Gln Ser Val
115 120 125Asn Tyr Leu Met Gly Thr Trp Pro Phe Gly Thr Ile Leu Cys Lys Ile
130 135 140Val Ile Ser Ile Asp Tyr Tyr Asn Met Phe Thr Ser Ile Phe Thr Leu145 150 155 160Cys Thr Met Ser Val Asp Arg Tyr Ile Ala Val Cys His Pro Val Lys
165 170 175Ala Leu Asp Phe Arg Thr Pro Arg Asn Ala Lys Ile Ile Asn Val Cys
180 185 190Asn Trp Ile Leu Ser Ser Ala Ile Gly Leu Pro Val Met Phe Met Ala
195 200 205Thr Thr Lys Tyr Arg Gln Gly Ser Ile Asp Cys Thr Leu Thr Phe Ser
210 215 220His Pro Thr Trp Tyr Trp Glu Asn Leu Val Lys Ile Cys Val Phe Ile225 230 235 240Phe Ala Phe Ile Met Pro Val Leu Ile Ile Thr Val Cys Tyr Gly Leu
245 250 255Met Ile Leu Arg Leu Lys Ser Val Arg Met Leu Ser Gly Ser Lys Glu
260 265 270Lys Asp Arg Asn Leu Arg Arg Ile Lys Arg Met Val Leu Val Val Val
275 280 285Ala Val Phe Ile Val Cys Trp Thr Pro Ile His Ile Tyr Val Ile Ile
290 295 300Lys Ala Leu Val Thr Ile Pro Glu Thr Thr Phe Gln Thr Val Ser Trp305 310 315 320His Phe Cys Ile Ala Leu Gly Tyr Thr Asn Ser Cys Leu Asn Pro Val
325 330 335Leu Tyr Ala Phe Leu Asp Glu Asn Phe Lys Arg Cys Phe Arg Glu Phe
340 345 350Cys Ile Pro Thr Ser Ser Asn Ile Glu Gln Gln Asn Ser Thr Arg Ile
355 360 365Arg Gln Asn Thr Arg Asp His Pro Ser Thr Ala Asn Thr Val Asp Arg
370 375 380Thr Asn His Gln Val Arg Ser Leu385 390<210>548<211>1278<212>DNA<213>智人(Homo sapiens)<400>548atggagccct cagccacccc aggggcccag atgggggtcc cccctggcag cagagagccg 60tcccctgtgc ctccagacta tgaagatgag tttctccgct atctgtggcg tgattatctg 120tacccaaaac agtatgagtg ggtcctcatc gcagcctatg tggctgtgtt cgtcgtggcc 180ctggtgggca acacgctggt ctgcctggcc gtgtggcgga accaccacat gaggacagtc 240accaactact tcattgtcaa cctgtccctg gctgacgttc tggtgactgc tatctgcctg 300ccggccagcc tgctggtgga catcactgag tcctggctgt tcggccatgc cctctgcaag 360gtcatcccct atctacaggc tgtgtccgtg tcagtggcag tgctaactct cagcttcatc 420gccctggacc gctggtatgc catctgccac ccactattgt tcaagagcac agcccggcgg 480gcccgtggct ccatcctggg catctgggct gtgtcgctgg ccatcatggt gccccaggct 540gcagtcatgg aatgcagcag tgtgctgcct gagctagcca accgcacacg gctcttctca 600gtctgtgatg aacgctgggc agatgacctc tatcccaaga tctaccacag ttgcttcttt 660attgtcacct acctggcccc actgggcctc atggccatgg cctatttcca gatattccgc 720aagctctggg gccgccagat ccccggcacc acctcagcac tggtgcggaa ctggaagcgc 780ccctcagacc agctggggga cctggagcag ggcctgagtg gagagcccca gccccggggc 840cgcgccttcc tggctgaagt gaagcagatg cgtgcacgga ggaagacaaa aaagatgctg 900atggtggtgc tgctggtctt cgccctctgc tacctgccca tcagcgtcct caatgtcctt 960aagagggtgt tcgggatgtt ccgccaagcc agtgaccgcg aagctgtcta cgcctgcttc 1020accttctccc actggctggt gtacgccaac agcgctgcca accccatcat ctacaacttc 1080ctcagtggca aattccggga gcagtttaag gctgccttct cctgctgcct gcctggcctg 1140ggtccctgcg gctctctgaa ggcccctagt ccccgctcct ctgccagcca caagtccttg 1200tccttgcaga gccgatgctc catctccaaa atctctgagc atgtggtgct caccagcgtc 1260accacagtgc tgccctga 1278<210>549<211>425<212>PRT<213>智人(Homo sapiens)<400>549Met Glu Pro Ser Ala Thr Pro Gly Ala Gln Met Gly Val Pro Pro Gly1 5 10 15Ser Arg Glu Pro Ser Pro Val Pro Pro Asp Tyr Glu Asp Glu Phe Leu
20 25 30Arg Tyr Leu Trp Arg Asp Tyr Leu Tyr Pro Lys Gln Tyr Glu Trp Val
35 40 45Leu Ile Ala Ala Tyr Val Ala Val Phe Val Val Ala Leu Val Gly Asn
50 55 60Thr Leu Val Cys Leu Ala Val Trp Arg Asn His His Met Arg Thr Val65 70 75 80Thr Asn Tyr Phe Ile Val Asn Leu Ser Leu Ala Asp Val Leu Val Thr
85 90 95Ala Ile Cys Leu Pro Ala Ser Leu Leu Val Asp Ile Thr Glu Ser Trp
100 105 110Leu Phe Gly His Ala Leu Cys Lys Val Ile Pro Tyr Leu Gln Ala Val
115 120 125Ser Val Ser Val Ala Val Leu Thr Leu Ser Phe Ile Ala Leu Asp Arg
130 135 140Trp Tyr Ala Ile Cys His Pro Leu Leu Phe Lys Ser Thr Ala Arg Arg145 150 155 160Ala Arg Gly Ser Ile Leu Gly Ile Trp Ala Val Ser Leu Ala Ile Met
165 170 175Val Pro Gln Ala Ala Val Met Glu Cys Ser Ser Val Leu Pro Glu Leu
180 185 190Ala Asn Arg Thr Arg Leu Phe Ser Val Cys Asp Glu Arg Trp Ala Asp
195 200 205Asp Leu Tyr Pro Lys Ile Tyr His Ser Cys Phe Phe Ile Val Thr Tyr
210 215 220Leu Ala Pro Leu Gly Leu Met Ala Met Ala Tyr Phe Gln Ile Phe Arg225 230 235 240Lys Leu Trp Gly Arg Gln Ile Pro Gly Thr Thr Ser Ala Leu Val Arg
245 250 255Asn Trp Lys Arg Pro Ser Asp Gln Leu Gly Asp Leu Glu Gln Gly Leu
260 265 270Ser Gly Glu Pro Gln Pro Arg Gly Arg Ala Phe Leu Ala Glu Val Lys
275 280 285Gln Met Arg Ala Arg Arg Lys Thr Lys Lys Met Leu Met Val Val Leu
290 295 300Leu Val Phe Ala Leu Cys Tyr Leu Pro Ile Ser Val Leu Asn Val Leu305 310 315 320Lys Arg Val Phe Gly Met Phe Arg Gln Ala Ser Asp Arg Glu Ala Val
325 330 335Tyr Ala Cys Phe Thr Phe Ser His Trp Leu Val Tyr Ala Asn Ser Ala
340 345 350Ala Asn Pro Ile Ile Tyr Asn Phe Leu Ser Gly Lys Phe Arg Glu Gln
355 360 365Phe Lys Ala Ala Phe Ser Cys Cys Leu Pro Gly Leu Gly Pro Cys Gly
370 375 380Ser Leu Lys Ala Pro Ser Pro Arg Ser Ser Ala Ser His Lys Ser Leu385 390 395 400Ser Leu Gln Ser Arg Cys Ser Ile Ser Lys Ile Ser Glu His Val Val
405 410 415Leu Thr Ser Val Thr Thr Val Leu Pro
420 425<210>550<211>1335<212>DNA<213>智人(Homo sapiens)<400>550atgtccggca ccaaattgga ggactccccc ccttgtcgca actggtcatc tgcttcggag 60ctgaatgaaa ctcaagagcc ctttttaaac cccaccgact atgacgacga ggaattcctg 120cggtacctgt ggagggaata cctgcacccg aaagaatatg agtgggtcct gatcgccggg 180tacatcatcg tgttcgtcgt ggctctcatt gggaacgtcc tggtttgtgt ggcagtgtgg 240aagaaccacc acatgaggac ggtaaccaac tacttcatag tcaatctttc tctggctgat 300gtgctcgtga ccatcacctg ccttccagcc acactggtcg tggatatcac tgagacctgg 360ttttttggac agtccctttg caaagtgatt ccttatctac agaccgtgtc ggtgtctgtg 420tctgtcctca cactgagctg tatcgccttg gatcggtggt atgcaatctg tcaccctttg 480atgtttaaga gcacagcaaa gcgggcccgt aacagcattg tcatcatctg gattgtctcc 540tgcattataa tgattcctca ggccatcgtc atggagtgca gcaccgtgtt cccaggctta 600gccaataaaa ccaccctctt tacggtgtgt gatgagcgct ggggtggtga aatttatccc 660aagatgtacc acatctgttt ctttctggtg acatacatgg caccactgtg tctcatggtg 720ttggcttatc tgcaaatatt tcgcaaactc tggtgtcgac agatccctgg aacatcatct 780gtagttcaga gaaaatggaa gcccctgcag cctgtttcac agcctcgagg gccaggacag 840ccaacgaagt cccggatgag cgctgtggcg gctgaaataa agcagatccg agccagaagg 900aaaacaaaac ggatgttgat ggttgtgctt ttggtatttg caatttgcta tctaccaatt 960agcatcctca atgtgctaaa gagagtattt gggatgtttg cccatactga agacagagag 1020actgtgtatg cctggtttac cttttcacac tggcttgtat atgccaatag tgctgcgaat 1080ccaattattt ataattttct cagtggaaaa tttcgagagg aatttaaagc tgcgttttct 1140tgctgttgcc ttggagttca ccatcgccag gaggatcggc tcaccagggg acgaactagc 1200acagagagcc ggaagtcctt gaccactcaa atcagcaact ttgataacat atcaaaactt 1260tctgagcaag ttgtgctcac tagcataagc acactcccag cagccaatgg agcaggacca 1320cttcaaaact ggtag 1335<210>551<211>444<212>PRT<213>智人(Homo sapiens)<400>551Met Ser Gly Thr Lys Leu Glu Asp Ser Pro Pro Cys Arg Asn Trp Ser1 5 10 15Ser Ala Ser Glu Leu Asn Glu Thr Gln Glu Pro Phe Leu Asn Pro Thr
20 25 30Asp Tyr Asp Asp Glu Glu Phe Leu Arg Tyr Leu Trp Arg Glu Tyr Leu
35 40 45His Pro Lys Glu Tyr Glu Trp Val Leu Ile Ala Gly Tyr Ile Ile Val
50 55 60Phe Val Val Ala Leu Ile Gly Asn Val Leu Val Cys Val Ala Val Trp65 70 75 80Lys Asn His His Met Arg Thr Val Thr Asn Tyr Phe Ile Val Asn Leu
85 90 95Ser Leu Ala Asp Val Leu Val Thr Ile Thr Cys Leu Pro Ala Thr Leu
100 105 110Val Val Asp Ile Thr Glu Thr Trp Phe Phe Gly Gln Ser Leu Cys Lys
115 120 125Val Ile Pro Tyr Leu Gln Thr Val Ser Val Ser Val Ser Val Leu Thr
130 135 140Leu Ser Cys Ile Ala Leu Asp Arg Trp Tyr Ala Ile Cys His Pro Leu145 150 155 160Met Phe Lys Ser Thr Ala Lys Arg Ala Arg Asn Ser Ile Val Ile Ile
165 170 175Trp Ile Val Ser Cys Ile Ile Met Ile Pro Gln Ala Ile Val Met Glu
180 185 190Cys Ser Thr Val Phe Pro Gly Leu Ala Asn Lys Thr Thr Leu Phe Thr
195 200 205Val Cys Asp Glu Arg Trp Gly Gly Glu Ile Tyr Pro Lys Met Tyr His
210 215 220Ile Cys Phe Phe Leu Val Thr Tyr Met Ala Pro Leu Cys Leu Met Val225 230 235 240Leu Ala Tyr Leu Gln Ile Phe Arg Lys Leu Trp Cys Arg Gln Ile Pro
245 250 255Gly Thr Ser Ser Val Val Gln Arg Lys Trp Lys Pro Leu Gln Pro Val
260 265 270Ser Gln Pro Arg Gly Pro Gly Gln Pro Thr Lys Ser Arg Met Ser Ala
275 280 285Val Ala Ala Glu Ile Lys Gln Ile Arg Ala Arg Arg Lys Thr Lys Arg
290 295 300Met Leu Met Val Val Leu Leu Val Phe Ala Ile Cys Tyr Leu Pro Ile305 310 315 320Ser Ile Leu Asn Val Leu Lys Arg Val Phe Gly Met Phe Ala His Thr
325 330 335Glu Asp Arg Glu Thr Val Tyr Ala Trp Phe Thr Phe Ser His Trp Leu
340 345 350Val Tyr Ala Asn Ser Ala Ala Asn Pro Ile Ile Tyr Asn Phe Leu Ser
355 360 365Gly Lys Phe Arg Glu Glu Phe Lys Ala Ala Phe Ser Cys Cys Cys Leu
370 375 380Gly Val His His Arg Gln Glu Asp Arg Leu Thr Arg Gly Arg Thr Ser385 390 395 400Thr Glu Ser Arg Lys Ser Leu Thr Thr Gln Ile Ser Asn Phe Asp Asn
405 410 415Ile Ser Lys Leu Ser Glu Gln Val Val Leu Thr Ser Ile Ser Thr Leu
420 425 430Pro Ala Ala Asn Gly Ala Gly Pro Leu Gln Asn Trp
435 440<210>552<211>1407<212>DNA<213>智人(Homo sapiens)<400>552atggctggtg tcgtgcacgt ttccctggct gctctcctcc tgctgcctat ggcccctgcc 60atgcattctg actgcatctt caagaaggag caagccatgt gcctggagaa gatccagagg 120gccaatgagc tgatgggctt caatgattcc tctccaggct gtcctgggat gtgggacaac 180atcacgtgtt ggaagcccgc ccatgtgggt gagatggtcc tggtcagctg ccctgagctc 240ttccgaatct tcaacccaga ccaagtctgg gagaccgaaa ccattggaga gtctgatttt 300ggtgacagta actccttaga tctctcagac atgggagtgg tgagccggaa ctgcacggag 360gatggctggt cggaaccctt ccctcattac tttgatgcct gtgggtttga tgaatatgaa 420tctgagactg gggaccagga ttattactac ctgtcagtga aggccctcta cacggttggc 480tacagcacat ccctcgtcac cctcaccact gccatggtca tcctttgtcg cttccggaag 540ctgcactgca cacgcaactt catccacatg aacctgtttg tgtcgttcat gctgagggcg 600atctccgtct tcatcaaaga ctggattctg tatgcggagc aggacagcaa ccactgcttc 660atctccactg tggaatgtaa ggccgtcatg gttttcttcc actactgtgt tgtgtccaac 720tacttctggc tgttcatcga gggcctgtac ctcttcactc tgctggtgga gaccttcttc 780cctgaaagga gatacttcta ctggtacacc atcattggct gggggacccc aactgtgtgt 840gtgacagtgt gggctacgct gagactctac tttgatgaca caggctgctg ggatatgaat 900gacagcacag ctctgtggtg ggtgatcaaa ggccctgtgg ttggctctat catggttaac 960tttgtgcttt ttattggcat tatcgtcatc cttgtgcaga aacttcagtc tccagacatg 1020ggaggcaatg agtccagcat ctacttgcga ctggcccggt cccccctgct gctcatccca 1080ctattcggaa tccactacac agtatttgcc ttctccccag agaatgtcag caaaagggaa 1140agactcgtgt ttgagctggg gctgggctcc ttccagggct ttgtggtggc tgttctctac 1200tgttttctga atggtgaggt acaagcggag atcaagcgaa aatggcgaag ctggaaggtg 1260aaccgttact tcgctgtgga cttcaagcac cgacacccgt ctctggccag cagtggggtg 1320aatgggggca cccagctctc catcctgagc aagagcagct cccaaatccg catgtctggc 1380ctccctgctg acaatctggc cacctga 1407<210>553<211>468<212>PRT<213>智人(Homo sapiens)<400>553Met Ala Gly Val Val His Val Ser Leu Ala Ala Leu Leu Leu Leu Pro1 5 10 15Met Ala Pro Ala Met His Ser Asp Cys Ile Phe Lys Lys Glu Gln Ala
20 25 30Met Cys Leu Glu Lys Ile Gln Arg Ala Asn Glu Leu Met Gly Phe Asn
35 40 45Asp Ser Ser Pro Gly Cys Pro Gly Met Trp Asp Asn Ile Thr Cys Trp
50 55 60Lys Pro Ala His Val Gly Glu Met Val Leu Val Ser Cys Pro Glu Leu65 70 75 80Phe Arg Ile Phe Asn Pro Asp Gln Val Trp Glu Thr Glu Thr Ile Gly
85 90 95Glu Ser Asp Phe Gly Asp Ser Asn Ser Leu Asp Leu Ser Asp Mer Gly
100 105 110Val Val Ser Arg Asn Cys Thr Glu Asp Gly Trp Ser Glu Pro Phe Pro
115 120 125His Tyr Phe Asp Ala Cys Gly Phe Asp Glu Tyr Glu Ser Glu Thr Gly
130 135 140Asp Gln Asp Tyr Tyr Tyr Leu Ser Val Lys Ala Leu Tyr Thr Val Gly145 150 155 160Tyr Ser Thr Ser Leu Val Thr Leu Thr Thr Ala Met Val Ile Leu Cys
165 170 175Arg Phe Arg Lys Leu His Cys Thr Arg Asn Phe Ile His Met Asn Leu
180 185 190Phe Val Ser Phe Met Leu Arg Ala Ile Ser Val Phe Ile Lys Asp Trp
195 200 205Ile Leu Tyr Ala Glu Gln Asp Ser Asn His Cys Phe Ile Ser Thr Val
210 215 220Glu Cys Lys Ala Val Met Val Phe Phe His Tyr Cys Val Val Ser Asn225 230 235 240Tyr Phe Trp Leu Phe Ile Glu Gly Leu Tyr Leu Phe Thr Leu Leu Val
245 250 255Glu Thr Phe Phe Pro Glu Arg Arg Tyr Phe Tyr Trp Tyr Thr Ile Ile
260 265 270Gly Trp Gly Thr Pro Thr Val Cys Val Thr Val Trp Ala Thr Leu Arg
275 280 285Leu Tyr Phe Asp Asp Thr Gly Cys Trp Asp Met Asn Asp Ser Thr Ala
290 295 300Leu Trp Trp Val Ile Lys Gly Pro Val Val Gly Ser Ile Met Val Asn305 310 315 320Phe Val Leu Phe Ile Gly Ile Ile Val Ile Leu Val Gln Lys Leu Gln
325 330 335Ser Pro Asp Met Gly Gly Asn Glu Ser Ser Ile Tyr Leu Arg Leu Ala
340 345 350Arg Ser Pro Leu Leu Leu Ile Pro Leu Phe Gly Ile His Tyr Thr Val
355 360 365Phe Ala Phe Ser Pro Glu Asn Val Ser Lys Arg Glu Arg Leu Val Phe
370 375 380Glu Leu Gly Leu Gly Ser Phe Gln Gly Phe Val Val Ala Val Leu Tyr385 390 395 400Cys Phe Leu Asn Gly Glu Val Gln Ala Glu Ile Lys Arg Lys Trp Arg
405 410 415Ser Trp Lys Val Asn Arg Tyr Phe Ala Val Asp Phe Lys His Arg His
420 425 430Pro Ser Leu Ala Ser Ser Gly Val Asn Gly Gly Thr Gln Leu Ser Ile
435 440 445Leu Ser Lys Ser Ser Ser Gln Ile Arg Met Ser Gly Leu Pro Ala Asp
450 455 460Asn Leu Ala Thr465<210>554<211>1029<212>DNA<213>智人(Homo sapiens)<400>554atggagccac atgactcctc ccacatggac tctgagttcc gatacactct cttcccgatt 60gtttacagca tcatctttgt gctcggggtc attgctaatg gctacgtgct gtgggtcttt 120gcccgcctgt acccttgcaa gaaattcaat gagataaaga tcttcatggt gaacctcacc 180atggcggaca tgctcttctt gatcaccctg ccactttgga ttgtctacta ccaaaaccag 240ggcaactgga tactccccaa attcctgtgc aacgtggctg gctgcctttt cttcatcaac 300acctactgct ctgtggcctt cctgggcgtc atcacttata accgcttcca ggcagtaact 360cggcccatca agactgctca ggccaacacc cgcaagcgtg gcatctcttt gtccttggtc 420atctgggtgg ccattgtggg agctgcatcc tacttcctca tcctggactc caccaacaca 480gtgcccgaca gtgctggctc aggcaacgtc actcgctgct ttgagcatta cgagaagggc 540agcgtgccag tcctcatcat ccacatcttc atcgtgttca gcttcttcct ggtcttcctc 600atcatcctct tctgcaacct ggtcatcatc cgtaccttgc tcatgcagcc ggtgcagcag 660cagcgcaacg ctgaagtcaa gcgccgggcg aagtggatgg tgtgcacggt cttggcggtg 720ttcatcatct gcttcgtgcc ccaccacgtg gtgcagctgc cctggaccct tgctgagctg 780ggcttccagg acagcaaatt ccaccaggcc attaatgatg cacatcaggt caccctctgc 840ctccttagca ccaactgtgt cttagaccct gttatctact gtttcctcac caagaagttc 900cgcaagcacc tcaccgaaaa gttctacagc atgcgcagta gccggaaatg ctcccgggcc 960accacggata cggtcactga agtggttgtg ccattcaacc agatccctgg caattccctc 1020aaaaattag 1029<210>555<211>342<212>PRT<213>智人(Homo sapiens)<400>555Met Glu Pro His Asp Ser Ser His Met Asp Ser Glu Phe Arg Tyr Thr1 5 10 15Leu Phe Pro Ile Val Tyr Ser Ile Ile Phe Val Leu Gly Val Ile Ala
20 25 30Asn Gly Tyr Val Leu Trp Val Phe Ala Arg Leu Tyr Pro Cys Lys Lys
35 40 45Phe Asn Glu Ile Lys Ile Phe Met Val Asn Leu Thr Met Ala Asp Met
50 55 60Leu Phe Leu Ile Thr Leu Pro Leu Trp Ile Val Tyr Tyr Gln Asn Gln65 70 75 80Gly Asn Trp Ile Leu Pro Lys Phe Leu Cys Asn Val Ala Gly Cys Leu
85 90 95Phe Phe Ile Asn Thr Tyr Cys Ser Val Ala Phe Leu Gly Val Ile Thr
100 105 110Tyr Asn Arg Phe Gln Ala Val Thr Arg Pro Ile Lys Thr Ala Gln Ala
115 120 125Asn Thr Arg Lys Arg Gly Ile Ser Leu Ser Leu Val Ile Trp Val Ala
130 135 140Ile Val Gly Ala Ala Ser Tyr Phe Leu Ile Leu Asp Ser Thr Asn Thr145 150 155 160Val Pro Asp Ser Ala Gly Ser Gly Asn Val Thr Arg Cys Phe Glu His
165 170 175Tyr Glu Lys Gly Ser Val Pro Val Leu Ile Ile His Ile Phe Ile Val
180 185 190Phe Ser Phe Phe Leu Val Phe Leu Ile Ile Leu Phe Cys Asn Leu Val
195 200 205Ile Ile Arg Thr Leu Leu Met Gln Pro Val Gln Gln Gln Arg Asn Ala
210 215 220Glu Val Lys Arg Arg Ala Lys Trp Met Val Cys Thr Val Leu Ala Val225 230 235 240Phe Ile Ile Cys Phe Val Pro His His Val Val Gln Leu Pro Trp Thr
245 250 255Leu Ala Glu Leu Gly Phe Gln Asp Ser Lys Phe His Gln Ala Ile Asn
260 265 270Asp Ala His Gln Val Thr Leu Cys Leu Leu Ser Thr Asn Cys Val Leu
275 280 285Asp Pro Val Ile Tyr Cys Phe Leu Thr Lys Lys Phe Arg Lys His Leu
290 295 300Thr Glu Lys Phe Tyr Ser Met Arg Ser Ser Arg Lys Cys Ser Arg Ala305 310 315 320Thr Thr Asp Thr Val Thr Glu Val Val Val Pro Phe Asn Gln Ile Pro
325 330 335Gly Asn Ser Leu Lys Asn
340<210>556<211>1209<212>DNA<213>智人(Homo sapiens)<400>556atgagccctt gcgggcccct caacctgagc ctggcgggcg aggcgaccac atgcgcggcg 60ccctgggtcc ccaacacgtc ggccgtgccg ccgtcgggcg cttcgcccgc gctgcccatc 120ttctccatga cgctgggcgc cgtgtccaac ctgctggcgc tggcgctgct ggcgcaggcc 180gcgggccgcc tgcgacgccg ccgctcggcc accaccttcc tgctgttcgt ggccagcctg 240ctggccaccg acctggcggg ccacgtgatc ccgggcgcgc tggtgctgcg tctgtacact 300gcggggcgcg ctccggccgg cggggcctgc cacttcctgg gcggctgcat ggtcttcttc 360ggcctgtgcc cgctgctgct gggctgtggc atggccgtgg agcgctgcgt gggcgtcacg 420cggccgctgc tccacgccgc gcgggtctcg gtcgcccgcg cgcgcctggc gctggccgcg 480gtggccgcgg tggccttggc cgtggcgctg ctgccgctgg cgcgcgtggg ccgctatgag 540ctgcagtacc cgggcacgtg gtgcttcatc ggcctgggtc ccccgggcgg ctggcgccag 600gcactgcttg ctggcctctt cgccagcctc ggcctggtcg cgctcctcgc cgcgctggtg 660tgcaacacgc tcagcggcct ggccctgcat cgcgcccgct ggcgacgccg ctcccgacgg 720cctcccccgg cctcaggccc cgacagccgg cgtcgctggg gggcgcacgg accccgctcg 780gcctccgcct cgtccgcctc gtccatcgct tcggcctcca ccttctttgg cggctctcgg 840agcagcggct cggcacgcag agctcgcgcc cacgacgtgg agatgaaggg ccagcttgtc 900ggtatcatgg tggtgtcgtg catctgctgg agcccaatgc tggtgttggt ggcgctggcc 960gtcggcggct ggagctctac ctccctgcag cggccactgt tcctggccgt gcgccttgcc 1020tcctggaacc agatcctgga cccttgggtg tacatcctac tgcgccaggc cgtgctgcgc 1080caactgcttc gcctcttgcc cccgagggcc ggagccaagg gcggccccgc ggggctgggc 1140ctaacaccga gcgcctggga ggccagctcg ctgcgcagct cccggcacag cggcctcagc 1200cacttctaa 1209<210>557<211>402<212>PRT<213>智人(Homo sapiens)<400>557Met Ser Pro Cys Gly Pro Leu Asn Leu Ser Leu Ala Gly Glu Ala Thr1 5 10 15Thr Cys Ala Ala Pro Trp Val Pro Asn Thr Ser Ala Val Pro Pro Ser
20 25 30Gly Ala Ser Pro Ala Leu Pro Ile Phe Ser Met Thr Leu Gly Ala Val
35 40 45Ser Asn Leu Leu Ala Leu Ala Leu Leu Ala Gln Ala Ala Gly Arg Leu
50 55 60Arg Arg Arg Arg Ser Ala Thr Thr Phe Leu Leu Phe Val Ala Ser Leu65 70 75 80Leu Ala Thr Asp Leu Ala Gly His Val Ile Pro Gly Ala Leu Val Leu
85 90 95Arg Leu Tyr Thr Ala Gly Arg Ala Pro Ala Gly Gly Ala Cys His Phe
100 105 110Leu Gly Gly Cys Met Val Phe Phe Gly Leu Cys Pro Leu Leu Leu Gly
115 120 125Cys Gly Met Ala Val Glu Arg Cys Val Gly Val Thr Arg Pro Leu Leu
130 135 140His Ala Ala Arg Val Ser Val Ala Arg Ala Arg Leu Ala Leu Ala Ala145 150 155 160Val Ala Ala Val Ala Leu Ala Val Ala Leu Leu Pro Leu Ala Arg Val
165 170 175Gly Arg Tyr Glu Leu Gln Tyr Pro Gly Thr Trp Cys Phe Ile Gly Leu
180 185 190Gly Pro Pro Gly Gly Trp Arg Gln Ala Leu Leu Ala Gly Leu Phe Ala
195 200 205Ser Leu Gly Leu Val Ala Leu Leu Ala Ala Leu Val Cys Asn Thr Leu
210 215 220Ser Gly Leu Ala Leu His Arg Ala Arg Trp Arg Arg Arg Ser Arg Arg225 230 235 240Pro Pro Pro Ala Ser Gly Pro Asp Ser Arg Arg Arg Trp Gly Ala His
245 250 255Gly Pro Arg Ser Ala Ser Ala Ser Ser Ala Ser Ser Ile Ala Ser Ala
260 265 270Ser Thr Phe Phe Gly Gly Ser Arg Ser Ser Gly Ser Ala Arg Arg Ala
275 280 285Arg Ala His Asp Val Glu Met Lys Gly Gln Leu Val Gly Ile Met Val
290 295 300Val Ser Cys Ile Cys Trp Ser Pro Met Leu Val Leu Val Ala Leu Ala305 310 315 320Val Gly Gly Trp Ser Ser Thr Ser Leu Gln Arg Pro Leu Phe Leu Ala
325 330 335Val Arg Leu Ala Ser Trp Asn Gln Ile Leu Asp Pro Trp Val Tyr Ile
340 345 350Leu Leu Arg Gln Ala Val Leu Arg Gln Leu Leu Arg Leu Leu Pro Pro
355 360 365Arg Ala Gly Ala Lys Gly Gly Pro Ala Gly Leu Gly Leu Thr Pro Ser
370 375 380Ala Trp Glu Ala Ser Ser Leu Arg Ser Ser Arg His Ser Gly Leu Ser385 390 395 400His Phe<210>558<211>1077<212>DNA<213>智人(Homo sapiens)<400>558atgggcaatg cctccaatga ctcccagtct gaggactgcg agacgcgaca gtggcttccc 60ccaggcgaaa gcccagccat cagctccgtc atgttctcgg ccggggtgct ggggaacctc 120atagcactgg cgctgctggc gcgccgctgg cggggggacg tggggtgcag cgccggccgc 180aggagctccc tctccttgtt ccacgtgctg gtgaccgagc tggtgttcac cgacctgctc 240gggacctgcc tcatcagccc agtggtactg gcttcgtacg cgcggaacca gaccctggtg 300gcactggcgc ccgagagccg cgcgtgcacc tacttcgctt tcgccatgac cttcttcagc 360ctggccacga tgctcatgct cttcgccatg gccctggagc gctacctctc gatcgggcac 420ccctacttct accagcgccg cgtctcggcc tccgggggcc tggccgtgct gcctgtcatc 480tatgcagtct ccctgctctt ctgctcgctg ccgctgctgg actatgggca gtacgtccag 540tactgccccg ggacctggtg cttcatccgg cacgggcgga ccgcttacct gcagctgtac 600gccaccctgc tgctgcttct cattgtctcg gtgctcgcct gcaacttcag tgtcattctc 660aacctcatcc gcatgcaccg ccgaagccgg agaagccgct gcggaccttc cctgggcagt 720ggccggggcg gccccggggc ccgcaggaga ggggaaaggg tgtccatggc ggaggagacg 780gaccacaaga ttctcctggc tatcatgacc atcaccttcg ccgtctgctc cttgcctttc 840acgatttttg catatatgaa tgaaacctct tcccgaaagg aaaaatggga cctccaagct 900cttaggtttt tatcaattaa ttcaataatt gacccttggg tctttgccat ccttaggcct 960cctgttctga gactaatgcg ttcagtcctc tgttgtcgga tttcattaag aacacaagat 1020gcaacacaaa cttcctgttc tacacagtca gatgccagta aacaggctga cctttga 1077<210>559<211>358<212>PRT<213>智人(Homo sapiens)<400>559Met Gly Asn Ala Ser Asn Asp Ser Gln Ser Glu Asp Cys Glu Thr Arg1 5 10 15Gln Trp Leu Pro Pro Gly Glu Ser Pro Ala Ile Ser Ser Val Met Phe
20 25 30Ser Ala Gly Val Leu Gly Asn Leu Ile Ala Leu Ala Leu Leu Ala Arg
35 40 45Arg Trp Arg Gly Asp Val Gly Cys Ser Ala Gly Arg Arg Ser Ser Leu
50 55 60Ser Leu Phe His Val Leu Val Thr Glu Leu Val Phe Thr Asp Leu Leu65 70 75 80Gly Thr Cys Leu Ile Ser Pro Val Val Leu Ala Ser Tyr Ala Arg Asn
85 90 95Gln Thr Leu Val Ala Leu Ala Pro Glu Ser Arg Ala Cys Thr Tyr Phe
100 105 110Ala Phe Ala Met Thr Phe Phe Ser Leu Ala Thr Met Leu Met Leu Phe
115 120 125Ala Met Ala Leu Glu Arg Tyr Leu Ser Ile Gly His Pro Tyr Phe Tyr
130 135 140Gln Arg Arg Val Ser Ala Ser Gly Gly Leu Ala Val Leu Pro Val Ile145 150 155 160Tyr Ala Val Ser Leu Leu Phe Cys Ser Leu Pro Leu Leu Asp Tyr Gly
165 170 175Gln Tyr Val Gln Tyr Cys Pro Gly Thr Trp Cys Phe Ile Arg His Gly
180 185 190Arg Thr Ala Tyr Leu Gln Leu Tyr Ala Thr Leu Leu Leu Leu Leu Ile
195 200 205Val Ser Val Leu Ala Cys Asn Phe Ser Val Ile Leu Asn Leu Ile Arg
210 215 220Met His Arg Arg Ser Arg Arg Ser Arg Cys Gly Pro Ser Leu Gly Ser225 230 235 240Gly Arg Gly Gly Pro Gly Ala Arg Arg Arg Gly Glu Arg Val Ser Met
245 250 255Ala Glu Glu Thr Asp His Lys Ile Leu Leu Ala Ile Met Thr Ile Thr
260 265 270Phe Ala Val Cys Ser Leu Pro Phe Thr Ile Phe Ala Tyr Met Asn Glu
275 280 285Thr Ser Ser Arg Lys Glu Lys Trp Asp Leu Gln Ala Leu Arg Phe Leu
290 295 300Ser Ile Asn Ser Ile Ile Asp Pro Trp Val Phe Ala Ile Leu Arg Pro305 310 315 320Pro Val Leu Arg Leu Met Arg Ser Val Leu Cys Cys Arg Ile Ser Leu
325 330 335Arg Thr Gln Asp Ala Thr Gln Thr Ser Cys Ser Thr Gln Ser Asp Ala
340 345 350Ser Lys Gln Ala Asp Leu
355<210>560<211>1467<212>DNA<213>智人(Homo sapiens)<400>560atgtccactc ccggggtcaa ttcgtccgcc tccttgagcc ccgaccggct gaacagccca 60gtgaccatcc cggcggtgat gttcatcttc ggggtggtgg gcaacctggt ggccatcgtg 120gtgctgtgca agtcgcgcaa ggagcagaag gagacgacct tctacacgct ggtatgtggg 180ctggctgtca ccgacctgtt gggcactttg ttggtgagcc cggtgaccat cgccacgtac 240atgaagggcc aatggcccgg gggccagccg ctgtgcgagt acagcacctt cattctgctc 300ttcttcagcc tgtccggcct cagcatcatc tgcgccatga gtgtcgagcg ctacctggcc 360atcaaccatg cctatttcta cagccactac gtggacaagc gattggcggg cctcacgctc 420tttgcagtct atgcgtccaa egtgctcttt tgcgcgctgc ccaacatggg tctcggtagc 480tcgcggctgc agtacccaga cacctggtgc ttcatcgact ggaccaccaa cgtgacggcg 540cacgccgcct actcctacat gtacgcgggc ttcagctcct tcctcattct cgccaccgtc 600ctctgcaacg tgcttgtgtg cggcgcgctg ctccgcatgc accgccagtt catgcgccgc 660acctcgctgg gcaccgagca gcaccacgcg gccgcggccg cctcggttgc ctcccggggc 720caccccgctg cctccccagc cttgccgcgc ctcagcgact ttcggcgccg ccggagcttc 780cgccgcatcg cgggcgccga gatccagatg aagatcttac tcattgccac ctccctggtg 840gtgctcatct gctccatccc gctcgtggtg cgagtattcg tcaaccagtt atatcagcca 900agtttggagc gagaagtcag taaaaatcca gatttgcagg ccatccgaat tgcttctgtg 960aaccccatcc tagacccctg gatatatatc ctcctgagaa agacagtgct cagtaaagca 1020atagagaaga tcaaatgcct cttctgccgc attggcgggt cccgcaggga gcgctccgga 1080cagcactgct cagacagtca aaggacatct tctgccatgt caggccactc tcgctccttc 1140atctcccggg agctgaagga gatcagcagt acatctcaga ccctcctgcc agacctctca 1200ctgccagacc tcagtgaaaa tggccttgga ggcaggaatt tgcttccagg tgtgcctggc 1260atgggcctgg cccaggaaga caccacctca ctgaggactt tgcgaatatc agagacctca 1320gactcttcac agggtcagga ctcagagagt gtcttactgg tggatgaggc tggtgggagc 1380ggcagggctg ggcctgcccc taaggggagc tccctgcaag tcacatttcc cagtgaaaca 1440ctgaacttat cagaaaaatg tatataa 1467<210>561<211>488<212>PRT<213>智人(Homo sapiens)<400>561Met Ser Thr Pro Gly Val Asn Ser Ser Ala Ser Leu Ser Pro Asp Arg1 5 10 15Leu Asn Ser Pro Val Thr Ile Pro Ala Val Met Phe Ile Phe Gly Val
20 25 30Val Gly Asn Leu Val Ala Ile Val Val Leu Cys Lys Ser Arg Lys Glu
35 40 45Gln Lys Glu Thr Thr Phe Tyr Thr Leu Val Cys Gly Leu Ala Val Thr
50 55 60Asp Leu Leu Gly Thr Leu Leu Val Ser Pro Val Thr Ile Ala Thr Tyr65 70 75 80Met Lys Gly Gln Trp Pro Gly Gly Gln Pro Leu Cys Glu Tyr Ser Thr
85 90 95Phe Ile Leu Leu Phe Phe Ser Leu Ser Gly Leu Ser Ile Ile Cys Ala
100 105 110Met Ser Val Glu Arg Tyr Leu Ala Ile Asn His Ala Tyr Phe Tyr Ser
115 120 125His Tyr Val Asp Lys Arg Leu Ala Gly Leu Thr Leu Phe Ala Val Tyr
130 135 140Ala Ser Asn Val Leu Phe Cys Ala Leu Pro Asn Met Gly Leu Gly Ser145 150 155 160Ser Arg Leu Gln Tyr Pro Asp Thr Trp Cys Phe Ile Asp Trp Thr Thr
165 170 175Asn Val Thr Ala His Ala Ala Tyr Ser Tyr Met Tyr Ala Gly Phe Ser
180 185 190Ser Phe Leu Ile Leu Ala Thr Val Leu Cys Asn Val Leu Val Cys Gly
195 200 205Ala Leu Leu Arg Met His Arg Gln Phe Met Arg Arg Thr Ser Leu Gly
210 215 220Thr Glu Gln His His Ala Ala Ala Ala Ala Ser Val Ala Ser Arg Gly225 230 235 240His Pro Ala Ala Ser Pro Ala Leu Pro Arg Leu Ser Asp Phe Arg Arg
245 250 255Arg Arg Ser Phe Arg Arg Ile Ala Gly Ala Glu Ile Gln Met Lys Ile
260 265 270Leu Leu Ile Ala Thr Ser Leu Val Val Leu Ile Cys Ser Ile Pro Leu
275 280 285Val Val Arg Val Phe Val Asn Gln Leu Tyr Gln Pro Ser Leu Glu Arg
290 295 300Glu Val Ser Lys Asn Pro Asp Leu Gln Ala Ile Arg Ile Ala Ser Val305 310 315 320Asn Pro Ile Leu Asp Pro Trp Ile Tyr Ile Leu Leu Arg Lys Thr Val
325 330 335Leu Ser Lys Ala Ile Glu Lys Ile Lys Cys Leu Phe Cys Arg Ile Gly
340 345 350Gly Ser Arg Arg Glu Arg Ser Gly Gln His Cys Ser Asp Ser Gln Arg
355 360 365Thr Ser Ser Ala Met Ser Gly His Ser Arg Ser Phe Ile Ser Arg Glu
370 375 380Leu Lys Glu Ile Ser Ser Thr Ser Gln Thr Leu Leu Pro Asp Leu Ser385 390 395 400Leu Pro Asp Leu Ser Glu Asn Gly Leu Gly Gly Arg Asn Leu Leu Pro
405 410 415Gly Val Pro Gly Met Gly Leu Ala Gln Glu Asp Thr Thr Ser Leu Arg
420 425 430Thr Leu Arg Ile Ser Glu Thr Ser Asp Ser Ser Gln Gly Gln Asp Ser
435 440 445Glu Ser Val Leu Leu Val Asp Glu Ala Gly Gly Ser Gly Arg Ala Gly
450 455 460Pro Ala Pro Lys Gly Ser Ser Leu Gln Val Thr Phe Pro Ser Glu Thr465 470 475 480Leu Asn Leu Ser Glu Lys Cys Ile
485<210>562<211>1782<212>DNA<213>智人(Homo sapiens)<400>562atggggaccg cccggatcgc acccggcctg gcgctcctgc tctgctgccc cgtgctcagc 60tccgcgtacg cgctggtgga tgcagatgac gtcatgacta aagaggaaca gatcttcctg 120ctgcaccgtg ctcaggccca gtgcgaaaaa cggctcaagg aggtcctgca gaggccagcc 180agcataatgg aatcagacaa gggatggaca tctgcgtcca catcagggaa gcccaggaaa 240gataaggcat ctgggaagct ctaccctgag tctgaggagg acaaggaggc acccactggc 300agcaggtacc gagggcgccc ctgtctgccg gaatgggacc acatcctgtg ctggccgctg 360ggggcaccag gtgaggtggt ggctgtgccc tgtccggact acatttatga cttcaatcac 420aaaggccatg cctaccgacg ctgtgaccgc aatggcagct gggagctggt gcctgggcac 480aacaggacgt gggccaacta cagcgagtgt gtcaaatttc tcaccaatga gactcgtgaa 540cgggaggtgt ttgaccgcct gggcatgatt tacaccgtgg gctactccgt gtccctggcg 600tccctcaccg tagctgtgct catcctggcc tactttaggc ggctgcactg cacgcgcaac 660tacatccaca tgcacctgtt cctgtccttc atgctgcgcg ccgtgagcat cttcgtcaag 720gacgctgtgc tctactctgg cgccacgctt gatgaggctg agcgcctcac cgaggaggag 780ctgcgcgcca tcgcccaggc gcccccgccg cctgccaccg ccgctgccgg ctacgcgggc 840tgcagggtgg ctgtgacctt cttcctttac ttcctggcca ccaactacta ctggattctg 900gtggaggggc tgtacctgca cagcctcatc ttcatggcct tcttctcaga gaagaagtac 960ctgtggggct tcacagtctt cggctggggt ctgcccgctg tcttcgtggc tgtgtgggtc 1020agtgtcagag ctaccctggc caacaccggg tgctgggact tgagctccgg gaacaaaaag 1080tggatcatcc aggtgcccat cctggcctcc attgtgctca acttcatcct cttcatcaat 1140atcgtccggg tgctcgccac caagctgcgg gagaccaacg ccggccggtg tgacacacgg 1200cagcagtacc ggaagctgct caaatccccg ctggtgctca tgcccctctt tggcgtccac 1260tacattgtct tcatggccac accatacacc gaggtctcag ggacgctctg gcaagtccag 1320atgcactatg agatgctctt caactccttc cagggatttt ttgtcgcaat catatactgt 1380ttctgcaatg gcgaggtaca agctgagatc aagaaatctt ggagccgctg gacactggca 1440ctggacttca agcgaaaggc acgcagcggg agcagcagct atagctacgg ccccatggtg 1500tcccacacaa gtgtgaccaa tgtcggcccc cgtgtgggac tcggcctgcc cctcagcccc 1560cgcctactgc ccactgccac caccaacggc caccctcagc tgcctggcca tgccaagcca 1620gggaccccag ccctggagac cctcgagacc acaccacctg ccatggctgc tcccaaggac 1680gatgggttcc tcaacggctc ctgctcaggc ctggacgagg aggcctctgg gcctgagcgg 1740ccacctgccc tgctacagga agagtgggag acagtcatgt ga 1782<210>563<211>593<212>PRT<213>智人(Homo sapiens)<400>563Met Gly Thr Ala Arg Ile Ala Pro Gly Leu Ala Leu Leu Leu Cys Cys1 5 10 15Pro Val Leu Ser Ser Ala Tyr Ala Leu Val Asp Ala Asp Asp Val Met
20 25 30Thr Lys Glu Glu Gln Ile Phe Leu Leu His Arg Ala Gln Ala Gln Cys
35 40 45Glu Lys Arg Leu Lys Glu Val Leu Gln Arg Pro Ala Ser Ile Met Glu
50 55 60Ser Asp Lys Gly Trp Thr Ser Ala Ser Thr Ser Gly Lys Pro Arg Lys65 70 75 80Asp Lys Ala Ser Gly Lys Leu Tyr Pro Glu Ser Glu Glu Asp Lys Glu
85 90 95Ala Pro Thr Gly Ser Arg Tyr Arg Gly Arg Pro Cys Leu Pro Glu Trp
100 105 110Asp His Ile Leu Cys Trp Pro Leu Gly Ala Pro Gly Glu Val Val Ala
115 120 125Val Pro Cys Pro Asp Tyr Ile Tyr Asp Phe Asn His Lys Gly His Ala
130 135 140Tyr Arg Arg Cys Asp Arg Asn Gly Ser Trp Glu Leu Val Pro Gly His145 150 155 160Asn Arg Thr Trp Ala Asn Tyr Ser Glu Cys Val Lys Phe Leu Thr Asn
165 170 175Glu Thr Arg Glu Arg Glu Val Phe Asp Arg Leu Gly Met Ile Tyr Thr
180 185 190Val Gly Tyr Ser Val Ser Leu Ala Ser Leu Thr Val Ala Val Leu Ile
195 200 205Leu Ala Tyr Phe Arg Arg Leu His Cys Thr Arg Asn Tyr Ile His Met
210 215 220His Leu Phe Leu Ser Phe Met Leu Arg Ala Val Ser Ile Phe Val Lys225 230 235 240Asp Ala Val Leu Tyr Ser Gly Ala Thr Leu Asp Glu Ala Glu Arg Leu
245 250 255Thr Glu Glu Glu Leu Arg Ala Ile Ala Gln Ala Pro Pro Pro Pro Ala
260 265 270Thr Ala Ala Ala Gly Tyr Ala Gly Cys Arg Val Ala Val Thr Phe Phe
275 280 285Leu Tyr Phe Leu Ala Thr Asn Tyr Tyr Trp Ile Leu Val Glu Gly Leu
290 295 300Tyr Leu His Ser Leu Ile Phe Met Ala Phe Phe Ser Glu Lys Lys Tyr305 310 315 320Leu Trp Gly Phe Thr Val Phe Gly Trp Gly Leu Pro Ala Val Phe Val
325 330 335Ala Val Trp Val Ser Val Arg Ala Thr Leu Ala Asn Thr Gly Cys Trp
340 345 350Asp Leu Ser Ser Gly Asn Lys Lys Trp Ile Ile Gln Val Pro Ile Leu
355 360 365Ala Ser Ile Val Leu Asn Phe Ile Leu Phe Ile Asn Ile Val Arg Val
370 375 380Leu Ala Thr Lys Leu Arg Glu Thr Asn Ala Gly Arg Cys Asp Thr Arg385 390 395 400Gln Gln Tyr Arg Lys Leu Leu Lys Ser Pro Leu Val Leu Met Pro Leu
405 410 415Phe Gly Val His Tyr Ile Val Phe Met Ala Thr Pro Tyr Thr Glu Val
420 425 430Ser Gly Thr Leu Trp Gln Val Gln Met His Tyr Glu Met Leu Phe Asn
435 440 445Ser Phe Gln Gly Phe Phe Val Ala Ile Ile Tyr Cys Phe Cys Asn Gly
450 455 460Glu Val Gln Ala Glu Ile Lys Lys Ser Trp Ser Arg Trp Thr Leu Ala465 470 475 480Leu Asp Phe Lys Arg Lys Ala Arg Ser Gly Ser Ser Ser Tyr Ser Tyr
485 490 495Gly Pro Met Val Ser His Thr Ser Val Thr Asn Val Gly Pro Arg Val
500 505 510Gly Leu Gly Leu Pro Leu Ser Pro Arg Leu Leu Pro Thr Ala Thr Thr
515 520 525Asn Gly His Pro Gln Leu Pro Gly His Ala Lys Pro Gly Thr Pro Ala
530 535 540Leu Glu Thr Leu Glu Thr Thr Pro Pro Ala Met Ala Ala Pro Lys Asp545 550 555 560Asp Gly Phe Leu Asn Gly Ser Cys Ser Gly Leu Asp Glu Glu Ala Ser
565 570 575Gly Pro Glu Arg Pro Pro Ala Leu Leu Gln Glu Glu Trp Glu Thr Val
580 585 590Met<210>564<211>1653<212>DNA<213>智人(Homo sapiens)<400>564atggccgggc tgggggcgtc gctccacgtc tggggttggc taatgctcgg cagctgcctc 60ctggccagag cccagctgga ttctgatggc accattacta tagaggagca gattgtcctt 120gtgctgaaag cgaaagtaca atgtgaactc aacatcacag ctcaactcca ggagggagaa 180ggtaattgtt tccctgaatg ggatggactc atttgttggc ccagaggaac agtggggaaa 240atatcggctg ttccatgccc tccttatatt tatgacttca accataaagg agttgctttc 300cgacactgta accccaatgg aacatgggat tttatgcaca gcttaaataa aacatgggcc 360aattattcag actgccttcg ctttctgcag ccagatatca gcataggaaa gcaagaattc 420tttgaacgcc tctatgtaat gtataccgtt ggctactcca tctcttttgg ttccttggct 480gtggctattc tcatcattgg ttacttcaga cgattgcatt gcactaggaa ctatatccac 540atgcacttat ttgtgtcttt catgctgaga gctacaagca tctttgtcaa agacagagta 600gtccatgctc acataggagt aaaggagctg gagtccctaa taatgcagga tgacccacaa 660aattccattg aggcaacttc tgtggacaaa tcacaatata tcgggtgcaa gattgctgtt 720gtgatgttta tttacttcct ggctacaaat tattattgga tcctggtgga aggtctctac 780ctgcataatc tcatctttgt ggctttcttt tcggacacca aatacctgtg gggcttcatc 840ttgataggct gggggtttcc agcagcattt gttgcagcat gggctgtggc acgagcaact 900ctggctgatg cgaggtgctg ggaacttagt gctggagaca tcaagtggat ttatcaagca 960ccgatcttag cagctattgg gctgaatttt attctgtttc tgaatacggt tagagttcta 1020gctaccaaaa tctgggagac caatgcagtt gggcatgaca caaggaagca atacaggaaa 1080ctggccaaat cgccactggt cctggtccta gtctttggag tgcattacat cgtgttcgta 1140tgcctgcctc actccttcac tgggctcggg tgggagatcc gcatgcactg tgagctcttc 1200ttcaactcct ttcagggttt ctttgtgtct atcatctact gctactgcaa tggagaggtt 1260caggcagagg tgaagaagat gtggagtcgg tggaatctct ccgtggactg gaaaaggaca 1320ccgccatgtg gcagccgcag atgcggctca gtgctcacca ccgtgacgca cagcaccagc 1380agccagtcac aggtggcggc cagcacacgc atggtgctta tctctggcaa agctgccaag 1440atcgccagca gacagcctga cagccacatc actttacctg gctatgtctg gagtaactca 1500gagcaggact gcctgccaca ctctttccac gaggagacca aggaagatag tgggaggcag 1560ggagatgata ttctaatgga gaagccttcc aggcctatgg aatctaaccc agacactgaa 1620ggatgccaag gagaaactga ggatgttctc tga 1653<210>565<211>550<212>PRT<213>智人(Homo sapiens)<400>565Met Ala Gly Leu Gly Ala Ser Leu His Val Trp Gly Trp Leu Met Leu1 5 10 15Gly Ser Cys Leu Leu Ala Arg Ala Gln Leu Asp Ser Asp Gly Thr Ile
20 25 30Thr Ile Glu Glu Gln Ile Val Leu Val Leu Lys Ala Lys Val Gln Cys
35 40 45Glu Leu Asn Ile Thr Ala Gln Leu Gln Glu Gly Glu Gly Asn Cys Phe
50 55 60Pro Glu Trp Asp Gly Leu Ile Cys Trp Pro Arg Gly Thr Val Gly Lys65 70 75 80Ile Ser Ala Val Pro Cys Pro Pro Tyr Ile Tyr Asp Phe Asn His Lys
85 90 95Gly Val Ala Phe Arg His Cys Asn Pro Asn Gly Thr Trp Asp Phe Met
100 105 110His Ser Leu Asn Lys Thr Trp Ala Asn Tyr Ser Asp Cys Leu Arg Phe
115 120 125Leu Gln Pro Asp Ile Ser Ile Gly Lys Gln Glu Phe Phe Glu Arg Leu
130 135 140Tyr Val Met Tyr Thr Val Gly Tyr Ser Ile Ser Phe Gly Ser Leu Ala145 150 155 160Val Ala Ile Leu Ile Ile Gly Tyr Phe Arg Arg Leu His Cys Thr Arg
165 170 175Asn Tyr Ile His Met His Leu Phe Val Ser Phe Met Leu Arg Ala Thr
180 185 190Ser Ile Phe Val Lys Asp Arg Val Val His Ala His Ile Gly Val Lys
195 200 205Glu Leu Glu Ser Leu Ile Met Gln Asp Asp Pro Gln Asn Ser Ile Glu
210 215 220Ala Thr Ser Val Asp Lys Ser Gln Tyr Ile Gly Cys Lys Ile Ala Val225 230 235 240Val Met Phe Ile Tyr Phe Leu Ala Thr Asn Tyr Tyr Trp Ile Leu Val
245 250 255Glu Gly Leu Tyr Leu His Asn Leu Ile Phe Val Ala Phe Phe Ser Asp
260 265 270Thr Lys Tyr Leu Trp Gly Phe Ile Leu Ile Gly Trp Gly Phe Pro Ala
275 280 285Ala Phe Val Ala Ala Trp Ala Val Ala Arg Ala Thr Leu Ala Asp Ala
290 295 300Arg Cys Trp Glu Leu Ser Ala Gly Asp Ile Lys Trp Ile Tyr Gln Ala305 310 315 320Pro Ile Leu Ala Ala Ile Gly Leu Asn Phe Ile Leu Phe Leu Asn Thr
325 330 335Val Arg Val Leu Ala Thr Lys Ile Trp Glu Thr Asn Ala Val Gly His
340 345 350Asp Thr Arg Lys Gln Tyr Arg Lys Leu Ala Lys Ser Pro Leu Val Leu
355 360 365Val Leu Val Phe Gly Val His Tyr Ile Val Phe Val Cys Leu Pro His
370 375 380Ser Phe Thr Gly Leu Gly Trp Glu Ile Arg Met His Cys Glu Leu Phe385 390 395 400Phe Asn Ser Phe Gln Gly Phe Phe Val Ser Ile Ile Tyr Cys Tyr Cys
405 410 415Asn Gly Glu Val Gln Ala Glu Val Lys Lys Met Trp Ser Arg Trp Asn
420 425 430Leu Ser Val Asp Trp Lys Arg Thr Pro Pro Cys Gly Ser Arg Arg Cys
435 440 445Gly Ser Val Leu Thr Thr Val Thr His Ser Thr Ser Ser Gln Ser Gln
450 455 460Val Ala Ala Ser Thr Arg Met Val Leu Ile Ser Gly Lys Ala Ala Lys465 470 475 480Ile Ala Ser Arg Gln Pro Asp Ser His Ile Thr Leu Pro Gly Tyr Val
485 490 495Trp Ser Asn Ser Glu Gln Asp Cys Leu Pro His Ser Phe His Glu Glu
500 505 510Thr Lys Glu Asp Ser Gly Arg Gln Gly Asp Asp Ile Leu Met Glu Lys
515 520 525Pro Ser Arg Pro Met Glu Ser Asn Pro Asp Thr Glu Gly Cys Gln Gly
530 535 540Glu Thr Glu Asp Val Leu545 550<210>566<211>1323<212>DNA<213>智人(Homo sapiens)<400>566atgcgtcccc acctgtcgcc gccgctgcag cagctactac tgccggtgct gctcgcctgc 60gccgcgcact cgactggagc ccttccccga ctatgtgacg tgctacaagt gctgtgggaa 120gagcaagacc agtgcctgca ggaactctcc agagagcaga caggagacct gggcacggag 180cagccagtgc caggttgtga ggggatgtgg gacaacataa gctgctggcc ctcttctgtg 240ccgggccgga tggtggaggt ggaatgcccg agattcctcc ggatgctcac cagcagaaat 300ggttccttgt tccgaaactg cacacaggat ggctggtcag aaaccttccc caggcctaat 360ctggcctgtg gcgttaatgt gaacgactct tccaacgaga agcggcactc ctacctgctg 420aagctgaaag tcatgtacac cgtgggctac agctcctccc tggtcatgct cctggtcgcc 480cttggcatcc tctgtgcttt ccggaggctc cactgcactc gcaactacat ccacatgcac 540ctgttcgtgt ccttcatcct tcgtgccctg tccaacttca tcaaggacgc cgtgctcttc 600tcctcagatg atgtcaccta ctgcgatccg cacagggcgg gctgcaagct ggtcatggtg 660ctgttccagt actgcatcat ggccaactac tcctggctgc tggtggaagg cctctacctt 720cacacactcc tcgccatctc cttcttctct gaaagaaagt acctccaggg atttgtggca 780ttcggatggg gttctccagc catttttgtt gctttgtggg ctattgccag acactttctg 840gaagatgttg ggtgctggga catcaatgcc aacgcatcca tctggtggat cattcgtggt 900cctgtgatcc tctccatcct gattaatttc atccttttca taaacattct aagaatcctg 960atgagaaaac ttagaaccca agaaacaaga ggaaatgaag tcagccatta taagcgcctg 1020gccaggtccc ctctcctgct gatccccctc tttggcatcc actacatcgt cttcgccttc 1080tccccagagg acgctatgga gatccagctg ttttttgaac tagcccttgg ctcattccag 1140ggactggtgg tggccgtcct ctactgcttc ctcaatgggg aggtgcagct ggaggttcag 1200aagaagtggc agcaatggca cctccgtgag ttcccactgc accccgtggc ctccttcagc 1260aacagcacca aggccagcca cttggagcag agccagggca cctgcaggac cagcatcatc 1320tga 1323<210>567<211>440<212>PRT<213>智人(Homo sapiens)<400>567Met Arg Pro His Leu Ser Pro Pro Leu Gln Gln Leu Leu Leu Pro Val1 5 10 15Leu Leu Ala Cys Ala Ala His Ser Thr Gly Ala Leu Pro Arg Leu Cys
20 25 30Asp Val Leu Gln Val Leu Trp Glu Glu Gln Asp Gln Cys Leu Gln Glu
35 40 45Leu Ser Arg Glu Gln Thr Gly Asp Leu Gly Thr Glu Gln Pro Val Pro
50 55 60Gly Cys Glu Gly Met Trp Asp Asn Ile Ser Cys Trp Pro Ser Ser Val65 70 75 80Pro Gly Arg Met Val Glu Val Glu Cys Pro Arg Phe Leu Arg Met Leu
85 90 95Thr Ser Arg Asn Gly Ser Leu Phe Arg Asn Cys Thr Gln Asp Gly Trp
100 105 110Ser Glu Thr Phe Pro Arg Pro Asn Leu Ala Cys Gly Val Asn Val Asn
115 120 125Asp Ser Ser Asn Glu Lys Arg His Ser Tyr Leu Leu Lys Leu Lys Val
130 135 140Met Tyr Thr Val Gly Tyr Ser Ser Ser Leu Val Met Leu Leu Val Ala145 150 155 160Leu Gly Ile Leu Cys Ala Phe Arg Arg Leu His Cys Thr Arg Asn Tyr
165 170 175Ile His Met His Leu Phe Val Ser Phe Ile Leu Arg Ala Leu Ser Asn
180 185 190Phe Ile Lys Asp Ala Val Leu Phe Ser Ser Asp Asp Val Thr Tyr Cys
195 200 205Asp Pro His Arg Ala Gly Cys Lys Leu Val Met Val Leu Phe Gln Tyr
210 215 220Cys Ile Met Ala Asn Tyr Ser Trp Leu Leu Val Glu Gly Leu Tyr Leu225 230 235 240His Thr Leu Leu Ala Ile Ser Phe Phe Ser Glu Arg Lys Tyr Leu Gln
245 250 255Gly Phe Val Ala Phe Gly Trp Gly Ser Pro Ala Ile Phe Val Ala Leu
260 265 270Trp Ala Ile Ala Arg His Phe Leu Glu Asp Val Gly Cys Trp Asp Ile
275 280 285Asn Ala Asn Ala Ser Ile Trp Trp Ile Ile Arg Gly Pro Val Ile Leu
290 295 300Ser Ile Leu Ile Asn Phe Ile Leu Phe Ile Asn Ile Leu Arg Ile Leu305 310 315 320Met Arg Lys Leu Arg Thr Gln Glu Thr Arg Gly Asn Glu Val Ser His
325 330 335Tyr Lys Arg Leu Ala Arg Ser Pro Leu Leu Leu Ile Pro Leu Phe Gly
340 345 350Ile His Tyr Ile Val Phe Ala Phe Ser Pro Glu Asp Ala Met Glu Ile
355 360 365Gln Leu Phe Phe Glu Leu Ala Leu Gly Ser Phe Gln Gly Leu Val Val
370 375 380Ala Val Leu Tyr Cys Phe Leu Asn Gly Glu Val Gln Leu Glu Val Gln385 390 395 400Lys Lys Trp Gln Gln Trp His Leu Arg Glu Phe Pro Leu His Pro Val
405 410 415Ala Ser Phe Ser Asn Ser Thr Lys Ala Ser His Leu Glu Gln Ser Gln
420 425 430Gly Thr Cys Arg Thr Ser Ile Ile
435 440<210>568<211>1176<212>DNA<213>智人(Homo sapiens)<400>568atgttcccca atggcaccgc ctcctctcct tcctcctctc ctagccccag cccgggcagc 60tgcggcgaag gcggcggcag caggggcccc ggggccggcg ctgcggacgg catggaggag 120ccagggcgaa atgcgtccca gaacgggacc ttgagcgagg gccagggcag cgccatcctg 180atctctttca tctactccgt ggtgtgcctg gtggggctgt gtgggaactc tatggtcatc 240tacgtgatcc tgcgctatgc caagatgaag acggccacca acatctacat cctaaatctg 300gccattgctg atgagctgct catgctcagc gtgcccttcc tagtcacctc cacgttgttg 360cgccactggc ccttcggtgc gctgctctgc cgcctcgtgc tcagcgtgga cgcggtcaac 420atgttcacca gcatctactg tctgactgtg ctcagcgtgg accgctacgt ggccgtggtg 480catcccatca aggcggcccg ctaccgccgg cccaccgtgg ccaaggtagt aaacctgggc 540gtgtgggtgc tatcgctgct cgtcatcctg cccatcgtgg tcttctctcg caccgcggcc 600aacagcgacg gcacggtggc ttgcaacatg ctcatgccag agcccgctca acgctggctg 660gtgggcttcg tgttgtacac atttctcatg ggcttcctgc tgcccgtggg ggctatctgc 720ctgtgctacg tgctcatcat tgctaagatg cgcatggtgg ccctcaaggc cggctggcag 780cagcgcaagc gctcggagcg caagatcaaa ttaatggtga tgatggtggt gatggtgttt 840gtcatctgct ggatgccttt ctacgtggtg cagctggtta acgtgtttgc tgagcaggac 900gacgccacgg tgagtcagct gtcggtcatc ctcggctatg ccaacagctg cgccaacccc 960atcctctatg gctttctctc agacaacttc aagcgctctt tccaacgcat cctatgcctc 1020agctggatgg acaacgccgc ggaggagccg gttgactatt acgccaccgc gctcaagagc 1080cgtgcctaca gtgtggaaga cttccaacct gagaacctgg agtccggcgg cgtcttccgt 1140aatggcacct gcacgtcccg gatcacgacg ctctga 1176<210>569<211>391<212>PRT<213>智人(Homo sapiens)<400>569Met Phe Pro Asn Gly Thr Ala Ser Ser Pro Ser Ser Ser Pro Ser Pro1 5 10 15Ser Pro Gly Ser Cys Gly Glu Gly Gly Gly Ser Arg Gly Pro Gly Ala
20 25 30Gly Ala Ala Asp Gly Met Glu Glu Pro Gly Arg Asn Ala Ser Gln Asn
35 40 45Gly Thr Leu Ser Glu Gly Gln Gly Ser Ala Ile Leu Ile Ser Phe Ile
50 55 60Tyr Ser Val Val Cys Leu Val Gly Leu Cys Gly Asn Ser Met Val Ile65 70 75 80Tyr Val Ile Leu Arg Tyr Ala Lys Met Lys Thr Ala Thr Asn Ile Tyr
85 90 95Ile Leu Asn Leu Ala Ile Ala Asp Glu Leu Leu Met Leu Ser Val Pro
100 105 110Phe Leu Val Thr Ser Thr Leu Leu Arg His Trp Pro Phe Gly Ala Leu
115 120 125Leu Cys Arg Leu Val Leu Ser Val Asp Ala Val Asn Met Phe Thr Ser
130 135 140Ile Tyr Cys Leu Thr Val Leu Ser Val Asp Arg Tyr Val Ala Val Val145 150 155 160His Pro Ile Lys Ala Ala Arg Tyr Arg Arg Pro Thr Val Ala Lys Val
165 170 175Val Asn Leu Gly Val Trp Val Leu Ser Leu Leu Val Ile Leu Pro Ile
180 185 190Val Val Phe Ser Arg Thr Ala Ala Asn Ser Asp Gly Thr Val Ala Cys
195 200 205Asn Met Leu Met Pro Glu Pro Ala Gln Arg Trp Leu Val Gly Phe Val
210 215 220Leu Tyr Thr Phe Leu Met Gly Phe Leu Leu Pro Val Gly Ala Ile Cys225 230 235 240Leu Cys Tyr Val Leu Ile Ile Ala Lys Met Arg Met Val Ala Leu Lys
245 250 255Ala Gly Trp Gln Gln Arg Lys Arg Ser Glu Arg Lys Ile Lys Leu Met
260 265 270Val Met Met Val Val Met Val Phe Val Ile Cys Trp Met Pro Phe Tyr
275 280 285Val Val Gln Leu Val Asn Val Phe Ala Glu Gln Asp Asp Ala Thr Val
290 295 300Ser Gln Leu Ser Val Ile Leu Gly Tyr Ala Asn Ser Cys Ala Asn Pro305 310 315 320Ile Leu Tyr Gly Phe Leu Ser Asp Asn Phe Lys Arg Ser Phe Gln Arg
325 330 335Ile Leu Cys Leu Ser Trp Met Asp Asn Ala Ala Glu Glu Pro Val Asp
340 345 350Tyr Tyr Ala Thr Ala Leu Lys Ser Arg Ala Tyr Ser Val Glu Asp Phe
355 360 365Gln Pro Glu Asn Leu Glu Ser Gly Gly Val Phe Arg Asn Gly Thr Cys
370 375 380Thr Ser Arg Ile Thr Thr Leu385 390<210>570<211>1110<212>DNA<213>智人(Homo sapiens)<400>570atggacatgg cggatgagcc actcaatgga agccacacat ggctatccat tccatttgac 60ctcaatggct ctgtggtgtc aaccaacacc tcaaaccaga cagagccgta ctatgacctg 120acaagcaatg cagtcctcac attcatctat tttgtggtct gcatcattgg gttgtgtggc 180aacacacttg tcatttatgt catcctccgc tatgccaaga tgaagaccat caccaacatt 240tacatcctca acctggccat cgcagatgag ctcttcatgc tgggtctgcc tttcttggct 300atgcaggtgg ctctggtcca ctggcccttt ggcaaggcca tttgccgggt ggtcatgact 360gtggatggca tcaatcagtt caccagcatc ttctgcctga cagtcatgag catcgaccga 420tacctggctg tggtccaccc catcaagtcg gccaagtgga ggagaccccg gacggccaag 480atgatcacca tggctgtgtg gggagtctct ctgctggtca tcttgcccat catgatatat 540gctgggctcc ggagcaacca gtgggggaga agcagctgca ccatcaactg gccaggtgaa 600tctggggctt ggtacacagg gttcatcatc tacactttca ttctggggtt cctggtaccc 660ctcaccatca tctgtctttg ctacctgttc attatcatca aggtgaagtc ctctggaatc 720cgagtgggct cctctaagag gaagaagtct gagaagaagg tcaaacgaat ggtgtccatc 780gtggtggctg tcttcatctt ctgctggctt cccttctaca tattcaacgt ttcttccgtc 840tccatggcca tcagccccac cccagccctt aaaggcatgt ttgactttgt ggtggtcctc 900acctatgcta acagctgtgc caaccctatc ctatatgcct tcttgtctga caacttcaag 960aagagcttcc agaatgtcct ctgcttggtc aaggtgagcg gcacagatga tggggagcgg 1020agtgacagta agcaggacaa atcccggctg aatgagacca cggagaccca gaggaccctc 1080ctcaatggag acctccaaac cagtatctga 1110<210>571<211>369<212>PRT<213>智人(Homo sapiens)<400>571Met Asp Met Ala Asp Glu Pro Leu Asn Gly Ser His Thr Trp Leu Ser1 5 10 15Ile Pro Phe Asp Leu Asn Gly Ser Val Val Ser Thr Asn Thr Ser Asn
20 25 30Gln Thr Glu Pro Tyr Tyr Asp Leu Thr Ser Asn Ala Val Leu Thr Phe
35 40 45Ile Tyr Phe Val Val Cys Ile Ile Gly Leu Cys Gly Asn Thr Leu Val
50 55 60Ile Tyr Val Ile Leu Arg Tyr Ala Lys Met Lys Thr Ile Thr Asn Ile65 70 75 80Tyr Ile Leu Asn Leu Ala Ile Ala Asp Glu Leu Phe Met Leu Gly Leu
85 90 95Pro Phe Leu Ala Met Gln Val Ala Leu Val His Trp Pro Phe Gly Lys
100 105 110Ala Ile Cys Arg Val Val Met Thr Val Asp Gly Ile Asn Gln Phe Thr
115 120 125Ser Ile Phe Cys Leu Thr Val Met Ser Ile Asp Arg Tyr Leu Ala Val
130 135 140Val His Pro Ile Lys Ser Ala Lys Trp Arg Arg Pro Arg Thr Ala Lys145 150 155 160Met Ile Thr Met Ala Val Trp Gly Val Ser Leu Leu Val Ile Leu Pro
165 170 175Ile Met Ile Tyr Ala Gly Leu Arg Ser Asn Gln Trp Gly Arg Ser Ser
180 185 190Cys Thr Ile Asn Trp Pro Gly Glu Ser Gly Ala Trp Tyr Thr Gly Phe
195 200 205Ile Ile Tyr Thr Phe Ile Leu Gly Phe Leu Val Pro Leu Thr Ile Ile
210 215 220Cys Leu Cys Tyr Leu Phe Ile Ile Ile Lys Val Lys Ser Ser Gly Ile225 230 235 240Arg Val Gly Ser Ser Lys Arg Lys Lys Ser Glu Lys Lys Val Lys Arg
245 250 255Met Val Ser Ile Val Val Ala Val Phe Ile Phe Cys Trp Leu Pro Phe
260 265 270Tyr Ile Phe Asn Val Ser Ser Val Ser Met Ala Ile Ser Pro Thr Pro
275 280 285Ala Leu Lys Gly Met Phe Asp Phe Val Val Val Leu Thr Tyr Ala Asn
290 295 300Ser Cys Ala Asn Pro Ile Leu Tyr Ala Phe Leu Ser Asp Asn Phe Lys305 310 315 320Lys Ser Phe Gln Asn Val Leu Cys Leu Val Lys Val Ser Gly Thr Asp
325 330 335Asp Gly Glu Arg Ser Asp Ser Lys Gln Asp Lys Ser Arg Leu Asn Glu
340 345 350Thr Thr Glu Thr Gln Arg Thr Leu Leu Asn Gly Asp Leu Gln Thr Ser
355 360 365Ile<210>572<211>1257<212>DNA<213>智人(Homo sapiens)<400>572atggacatgc ttcatccatc atcggtgtcc acgacctcag aacctgagaa tgcctcctcg 60gcctggcccc cagatgccac cctgggcaac gtgtcggcgg gcccaagccc ggcagggctg 120gccgtcagtg gcgttctgat ccccctggtc tacctggtgg tgtgcgtggt gggcctgctg 180ggtaactcgc tggtcatcta tgtggtcctg cggcacacgg ccagcccttc agtcaccaac 240gtctacatcc tcaacctggc gctggccgac gagctcttca tgctggggct gcccttcctg 300gccgcccaga acgccctgtc ctactggccc ttcggctccc tcatgtgccg cctggtcatg 360gcggtggatg gcatcaacca gttcaccagc atattctgcc tgactgtcat gagcgtggac 420cgctacctgg ccgtggtaca tcccacccgc tcggcccgct ggcgcacagc tccggtggcc 480cgcacggtca gcgcggctgt gtgggtggcc tcagccgtgg tggtgctgcc cgtggtggtc 540ttctcgggag tgccccgcgg catgagcacc tgccacatgc agtggcccga gccggcggcg 600gcctggcgag ccggcttcat catctacacg gccgcactgg gcttcttcgg gccgctgctg 660gtcatctgcc tctgctacct gctcatcgtg gtgaaggtgc gctcagctgg gcgccgggtg 720tgggcaccct cgtgccagcg gcgccggcgc tccgaacgca gggtcaagcg catggtggtg 780gccgtggtgg cgctcttcgt gctctgctgg atgcccttct acgtgctcaa catcgtcaac 840gtggtgtgcc cactgcccga ggagcctgcc ttctttgggc tctacttcct ggtggtggcg 900ctgccctatg ccaacagctg tgccaacccc atcctttatg gcttcctctc ctaccgcttc 960aagcagggct tccgcagggt cctgctgcgg ccctcccgcc gtgtgcgcag ccaggagccc 1020actgtggggc ccccggagaa gactgaggag gaggatgagg aggaggagga tggggaggag 1080agcagggagg ggggcaaggg gaaggagatg aacggccggg tcagccagat cacgcagcct 1140ggcaccagcg ggcaggagcg gccgcccagc agagtggcca gcaaggagca gcagctccta 1200ccccaagagg cttccactgg ggagaagtcc agcacgatgc gcatcagcta cctgtag 1257<210>573<211>418<212>PRT<213>智人(Homo sapiens)<400>573Met Asp Met Leu His Pro Ser Ser Val Ser Thr Thr Ser Glu Pro Glu1 5 10 15Asn Ala Ser Ser Ala Trp Pro Pro Asp Ala Thr Leu Gly Asn Val Ser
20 25 30Ala Gly Pro Ser Pro Ala Gly Leu Ala Val Ser Gly Val Leu Ile Pro
35 40 45Leu Val Tyr Leu Val Val Cys Val Val Gly Leu Leu Gly Asn Ser Leu
50 55 60Val Ile Tyr Val Val Leu Arg His Thr Ala Ser Pro Ser Val Thr Asn65 70 75 80Val Tyr Ile Leu Asn Leu Ala Leu Ala Asp Glu Leu Phe Met Leu Gly
85 90 95Leu Pro Phe Leu Ala Ala Gln Asn Ala Leu Ser Tyr Trp Pro Phe Gly
100 105 110Ser Leu Met Cys Arg Leu Val Met Ala Val Asp Gly Ile Asn Gln Phe
115 120 125Thr Ser Ile Phe Cys Leu Thr Val Met Ser Val Asp Arg Tyr Leu Ala
130 135 140Val Val His Pro Thr Arg Ser Ala Arg Trp Arg Thr Ala Pro Val Ala145 150 155 160Arg Thr Val Ser Ala Ala Val Trp Val Ala Ser Ala Val Val Val Leu
165 170 175Pro Val Val Val Phe Ser Gly Val Pro Arg Gly Met Ser Thr Cys His
180 185 190Met Gln Trp Pro Glu Pro Ala Ala Ala Trp Arg Ala Gly Phe Ile Ile
195 200 205Tyr Thr Ala Ala Leu Gly Phe Phe Gly Pro Leu Leu Val Ile Cys Leu
210 215 220Cys Tyr Leu Leu Ile Val Val Lys Val Arg Ser Ala Gly Arg Arg Val225 230 235 240Trp Ala Pro Ser Cys Gln Arg Arg Arg Arg Ser Glu Arg Arg Val Lys
245 250 255Arg Met Val Val Ala Val Val Ala Leu Phe Val Leu Cys Trp Met Pro
260 265 270Phe Tyr Val Leu Asn Ile Val Asn Val Val Cys Pro Leu Pro Glu Glu
275 280 285Pro Ala Phe Phe Gly Leu Tyr Phe Leu Val Val Ala Leu Pro Tyr Ala
290 295 300Asn Ser Cys Ala Asn Pro Ile Leu Tyr Gly Phe Leu Ser Tyr Arg Phe305 310 315 320Lys Gln Gly Phe Arg Arg Val Leu Leu Arg Pro Ser Arg Arg Val Arg
325 330 335Ser Gln Glu Pro Thr Val Gly Pro Pro Glu Lys Thr Glu Glu Glu Asp
340 345 350Glu Glu Glu Glu Asp Gly Glu Glu Ser Arg Glu Gly Gly Lys Gly Lys
355 360 365Glu Met Asn Gly Arg Val Ser Gln Ile Thr Gln Pro Gly Thr Ser Gly
370 375 380Gln Glu Arg Pro Pro Ser Arg Val Ala Ser Lys Glu Gln Gln Leu Leu385 390 395 400Pro Gln Glu Ala Ser Thr Gly Glu Lys Ser Ser Thr Met Arg Ile Ser
405 410 415Tyr Leu<210>574<211>1167<212>DNA<213>智人(Homo sapiens)<400>574atgagcgccc cctcgacgct gccccccggg ggcgaggaag ggctggggac ggcctggccc 60tctgcagcca atgccagtag cgctccggcg gaggcggagg aggcggtggc ggggcccggg 120gacgcgcggg cggcgggcat ggtcgctatc cagtgcatct acgcgctggt gtgcctggtg 180gggctggtgg gcaacgccct ggtcatcttc gtgatccttc gctacgccaa gatgaagacg 240gctaccaaca tctacctgct caacctggcc gtagccgacg agctcttcat gctgagcgtg 300cccttcgtgg cctcgtcggc cgccctgcgc cactggccct tcggctccgt gctgtgccgc 360gcggtgctca gcgtcgacgg cctcaacatg ttcaccagcg tcttctgtct caccgtgctc 420agcgtggacc gctacgtggc cgtggtgcac cctctgcgcg cggcgaccta ccggcggccc 480agcgtggcca agctcatcaa cctgggcgtg tggctggcat ccctgttggt cactctcccc 540atcgccatct tcgcagacac cagaccggct cgcggcggcc aggccgtggc ctgcaacctg 600cagtggccac acccggcctg gtcggcagtc ttcgtggtct acactttcct gctgggcttc 660ctgctgcccg tgctggccat tggcctgtgc tacctgctca tcgtgggcaa gatgcgcgcc 720gtggccctgc gcgctggctg gcagcagcgc aggcgctcgg agaagaaaat caaaaggctg 780gtgctgatgg tcgtggtcgt ctttgtgctc tgctggatgc ctttctacgt ggtgcagctg 840ctgaacctcg tcgtgaccag ccttgatgcc accgtcaacc acgtgtccct tatcctcagc 900tatgccaaca gctgcgccaa ccctattctc tatggcttcc tctccgacaa cttccgccga 960tccttccagc gggttctctg cctgcgctgc tgcctcctgg aaggtgctgg aggtgctgag 1020gaggagcccc tggactacta tgccactgct ctcaagagca aaggtggggc agggtgcatg 1080tgccccccac tcccctgcca gcaggaagcc ctgcaaccag aacccggccg caagcgcatc 1140cccctcacca ggaccaccac cttctga 1167<210>575<211>388<212>PRT<213>智人(Homo sapiens)<400>575Met Ser Ala Pro Ser Thr Leu Pro Pro Gly Gly Glu Glu Gly Leu Gly1 5 10 15Thr Ala Trp Pro Ser Ala Ala Asn Ala Ser Ser Ala Pro Ala Glu Ala
20 25 30Glu Glu Ala Val Ala Gly Pro Gly Asp Ala Arg Ala Ala Gly Met Val
35 40 45Ala Ile Gln Cys Ile Tyr Ala Leu Val Cys Leu Val Gly Leu Val Gly
50 55 60Asn Ala Leu Val Ile Phe Val Ile Leu Arg Tyr Ala Lys Met Lys Thr65 70 75 80Ala Thr Asn Ile Tyr Leu Leu Asn Leu Ala Val Ala Asp Glu Leu Phe
85 90 95Met Leu Ser Val Pro Phe Val Ala Ser Ser Ala Ala Leu Arg His Trp
100 105 110Pro Phe Gly Ser Val Leu Cys Arg Ala Val Leu Ser Val Asp Gly Leu
115 120 125Asn Met Phe Thr Ser Val Phe Cys Leu Thr Val Leu Ser Val Asp Arg
130 135 140Tyr Val Ala Val Val His Pro Leu Arg Ala Ala Thr Tyr Arg Arg Pro145 150 155 160Ser Val Ala Lys Leu Ile Asn Leu Gly Val Trp Leu Ala Ser Leu Leu
165 170 175Val Thr Leu Pro Ile Ala Ile Phe Ala Asp Thr Arg Pro Ala Arg Gly
180 185 190Gly Gln Ala Val Ala Cys Asn Leu Gln Trp Pro His Pro Ala Trp Ser
195 200 205Ala Val Phe Val Val Tyr Thr Phe Leu Leu Gly Phe Leu Leu Pro Val
210 215 220Leu Ala Ile Gly Leu Cys Tyr Leu Leu Ile Val Gly Lys Met Arg Ala225 230 235 240Val Ala Leu Arg Ala Gly Trp Gln Gln Arg Arg Arg Ser Glu Lys Lys
245 250 255Ile Lys Arg Leu Val Leu Met Val Val Val Val Phe Val Leu Cys Trp
260 265 270Met Pro Phe Tyr Val Val Gln Leu Leu Asn Leu Val Val Thr Ser Leu
275 280 285Asp Ala Thr Val Asn His Val Ser Leu Ile Leu Ser Tyr Ala Asn Ser
290 295 300Cys Ala Asn Pro Ile Leu Tyr Gly Phe Leu Ser Asp Asn Phe Arg Arg305 310 315 320Ser Phe Gln Arg Val Leu Cys Leu Arg Cys Cys Leu Leu Glu Gly Ala
325 330 335Gly Gly Ala Glu Glu Glu Pro Leu Asp Tyr Tyr Ala Thr Ala Leu Lys
340 345 350Ser Lys Gly Gly Ala Gly Cys Met Cys Pro Pro Leu Pro Cys Gln Gln
355 360 365Glu Ala Leu Gln Pro Glu Pro Gly Arg Lys Arg Ile Pro Leu Thr Arg
370 375 380Thr Thr Thr Phe385<210>576<211>1095<212>DNA<213>智人(Homo sapiens)<400>576atggagcccc tgttcccagc ctccacgccc agctggaacg cctcctcccc gggggctgcc 60tctggaggcg gtgacaacag gacgctggtg gggccggcgc cctcggcagg ggcccgggcg 120gtgctggtgc ccgtgctgta cctgctggtg tgtgcggccg ggctgggcgg gaacacgctg 180gtcatctacg tggtgctgcg cttcgccaag atgaagaccg tcaccaacat ctacattctc 240aacctggcag tggccgacgt cctgtacatg ctggggctgc ctttcctggc cacgcagaac 300gccgcgtcct tctggccctt cggccccgtc ctgtgccgcc tggtcatgac gctggacggc 360gtcaaccagt tcaccagtgt cttctgcctg acagtcatga gcgtggaccg ctacctggca 420gtggtgcacc cgctgagctc ggcccgctgg cgccgcccgc gtgtggccaa gctggcgagc 480gccgcggcct gggtcctgtc tctgtgcatg tcgctgccgc tcctggtgtt cgcggacgtg 540caggagggcg gtacctgcaa cgccagctgg ccggagcccg tggggctgtg gggcgccgtc 600ttcatcatct acacggccgt gctgggcttc ttcgcgccgc tgctggtcat ctgcctgtgc 660tacctgctca tcgtggtgaa ggtgagggcg gcgggcgtgc gcgtgggctg cgtgcggcgg 720cgctcggagc ggaaggtgaa gcgcatggtg ttggtggtgg tgctggtgtt tgcgggatgt 780tggctgccct tcttcaccgt caacatcgtc aacctggccg tggcgctgcc ccaggagccc 840gcctccgccg gcctctactt cttcgtggtc atcctctcct acgccaacag ctgtgccaac 900cccgtcctct acggcttcct ctctgacaac ttccgccaga gcttccagaa ggttctgtgc 960ctccgcaagg gctctggtgc caaggacgct gacgccacgg agccgcgtcc agacaggatc 1020cggcagcagc aggaggccac gccgcccgcg caccgcgccg cagccaacgg gcttatgcag 1080accagcaagc tgtga 1095<210>577<211>364<212>PRT<213>智人(Homo sapiens)<400>577Met Glu Pro Leu Phe Pro Ala Ser Thr Pro Ser Trp Asn Ala Ser Ser1 5 10 15Pro Gly Ala Ala Ser Gly Gly Gly Asp Asn Arg Thr Leu Val Gly Pro
20 25 30Ala Pro Ser Ala Gly Ala Arg Ala Val Leu Val Pro Val Leu Tyr Leu
35 40 45Leu Val Cys Ala Ala Gly Leu Gly Gly Asn Thr Leu Val Ile Tyr Val
50 55 60Val Leu Arg Phe Ala Lys Met Lys Thr Val Thr Asn Ile Tyr Ile Leu65 70 75 80Asn Leu Ala Val Ala Asp Val Leu Tyr Met Leu Gly Leu Pro Phe Leu
85 90 95Ala Thr Gln Asn Ala Ala Ser Phe Trp Pro Phe Gly Pro Val Leu Cys
100 105 110Arg Leu Val Met Thr Leu Asp Gly Val Asn Gln Phe Thr Ser Val Phe
115 120 125Cys Leu Thr Val Met Ser Val Asp Arg Tyr Leu Ala Val Val His Pro
130 135 140Leu Ser Ser Ala Arg Trp Arg Arg Pro Arg Val Ala Lys Leu Ala Ser145 150 155 160Ala Ala Ala Trp Val Leu Ser Leu Cys Met Ser Leu Pro Leu Leu Val
165 170 175Phe Ala Asp Val Gln Glu Gly Gly Thr Cys Asn Ala Ser Trp Pro Glu
180 185 190Pro Val Gly Leu Trp Gly Ala Val Phe Ile Ile Tyr Thr Ala Val Leu
195 200 205Gly Phe Phe Ala Pro Leu Leu Val Ile Cys Leu Cys Tyr Leu Leu Ile
210 215 220Val Val Lys Val Arg Ala Ala Gly Val Arg Val Gly Cys Val Arg Arg225 230 235 240Arg Ser Glu Arg Lys Val Lys Arg Met Val Leu Val Val Val Leu Val
245 250 255Phe Ala Gly Cys Trp Leu Pro Phe Phe Thr Val Asn Ile Val Asn Leu
260 265 270Ala Val Ala Leu Pro Gln Glu Pro Ala Ser Ala Gly Leu Tyr Phe Phe
275 280 285Val Val Ile Leu Ser Tyr Ala Asn Ser Cys Ala Asn Pro Val Leu Tyr
290 295 300Gly Phe Leu Ser Asp Asn Phe Arg Gln Ser Phe Gln Lys Val Leu Cys305 310 315 320Leu Arg Lys Gly Ser Gly Ala Lys Asp Ala Asp Ala Thr Glu Pro Arg
325 330 335Pro Asp Arg Ile Arg Gln Gln Gln Glu Ala Thr Pro Pro Ala His Arg
340 345 350Ala Ala Ala Asn Gly Leu Met Gln Thr Ser Lys Leu
355 360<210>578<211>1374<212>DNA<213>智人(Homo sapiens)<400>578atgcgcccgc caagtccgct gcccgcccgc tggctatgcg tgctggcagg cgccctcgcc 60tgggcccttg ggccggcggg cggccaggcg gccaggctgc aggaggagtg tgactatgtg 120cagatgatcg aggtgcagca caagcagtgc ctggaggagg cccagctgga gaatgagaca 180ataggctgca gcaagatgtg ggacaacctc acctgctggc cagccacccc tcggggccag 240gtagttgtct tggcctgtcc cctcatcttc aagctcttct cctccattca aggccgcaat 300gtaagccgca gctgcaccga cgaaggctgg acgcacctgg agcctggccc gtaccccatt 360gcctgtggtt tggatgacaa ggcagcgagt ttggatgagc agcagaccat gttctacggt 420tctgtgaaga ccggctacac catcggctac ggcctgtccc tcgccaccct tctggtcgcc 480acagctatcc tgagcctgtt caggaagctc cactgcacgc ggaactacat ccacatgcac 540ctcttcatat ccttcatcct gagggctgcc gctgtcttca tcaaagactt ggccctcttc 600gacagcgggg agtcggacca gtgctccgag ggctcggtgg gctgtaaggc agccatggtc 660tttttccaat attgtgtcat ggctaacttc ttctggctgc tggtggaggg cctctacctg 720tacaccctgc ttgccgtctc cttcttctct gagcggaagt acttctgggg gtacatactc 780atcggctggg gggtacccag cacattcacc atggtgtgga ccatcgccag gatccatttt 840gaggattatg ggtgctggga caccatcaac tcctcactgt ggtggatcat aaagggcccc 900atcctcacct ccatcttggt aaacttcatc ctgtttattt gcatcatccg aatcctgctt 960cagaaactgc ggcccccaga tatcaggaag agtgacagca gtccatactc aaggctagcc 1020aggtccccac tcctgctgat ccccctgttt ggagtacact acatcatgtt cgccttcttt 1080ccggacaatt ttaagcctga agtgaagatg gtctttgagc tcgtcgtggg gtctttccag 1140ggttttgtgg tggctatcct ctactgcttc ctcaatggtg aggtgcaggc ggagctgagg 1200cggaagtggc ggcgctggca cctgcagggc gtcctgggct ggaaccccaa ataccggcac 1260ccgtcgggag gcagcaacgg cgccacgtgc agcacgcagg tttccatgct gacccgcgtc 1320agcccaggtg cccgccgctc ctccagcttc caagccgaag tctccctggt ctga 1374<210>579<211>457<212>PRT<213>智人(Homo sapiens)<400>579Met Arg Pro Pro Ser Pro Leu Pro Ala Arg Trp Leu Cys Val Leu Ala1 5 10 15Gly Ala Leu Ala Trp Ala Leu Gly Pro Ala Gly Gly Gln Ala Ala Arg
20 25 30Leu Gln Glu Glu Cys Asp Tyr Val Gln Met Ile Glu Val Gln His Lys
35 40 45Gln Cys Leu Glu Glu Ala Gln Leu Glu Asn Glu Thr Ile Gly Cys Ser
50 55 60Lys Met Trp Asp Asn Leu Thr Cys Trp Pro Ala Thr Pro Arg Gly Gln65 70 75 80Val Val Val Leu Ala Cys Pro Leu Ile Phe Lys Leu Phe Ser Ser Ile
85 90 95Gln Gly Arg Asn Val Ser Arg Ser Cys Thr Asp Glu Gly Trp Thr His
100 105 110Leu Glu Pro Gly Pro Tyr Pro Ile Ala Cys Gly Leu Asp Asp Lys Ala
115 120 125Ala Ser Leu Asp Glu Gln Gln Thr Met Phe Tyr Gly Ser Val Lys Thr
130 135 140Gly Tyr Thr Ile Gly Tyr Gly Leu Ser Leu Ala Thr Leu Leu Val Ala145 150 155 160Thr Ala Ile Leu Ser Leu Phe Arg Lys Leu His Cys Thr Arg Asn Tyr
165 170 175Ile His Met His Leu Phe Ile Ser Phe Ile Leu Arg Ala Ala Ala Val
180 185 190Phe Ile Lys Asp Leu Ala Leu Phe Asp Ser Gly Glu Ser Asp Gln Cys
195 200 205Ser Glu Gly Ser Val Gly Cys Lys Ala Ala Met Val Phe Phe Gln Tyr
210 215 220Cys Val Met Ala Asn Phe Phe Trp Leu Leu Val Glu Gly Leu Tyr Leu225 230 235 240Tyr Thr Leu Leu Ala Val Ser Phe Phe Ser Glu Arg Lys Tyr Phe Trp
245 250 255Gly Tyr Ile Leu Ile Gly Trp Gly Val Pro Ser Thr Phe Thr Met Val
260 265 270Trp Thr Ile Ala Arg Ile His Phe Glu Asp Tyr Gly Cys Trp Asp Thr
275 280 285Ile Asn Ser Ser Leu Trp Trp Ile Ile Lys Gly Pro Ile Leu Thr Ser
290 295 300Ile Leu Val Asn Phe Ile Leu Phe Ile Cys Ile Ile Arg Ile Leu Leu305 310 315 320Gln Lys Leu Arg Pro Pro Asp Ile Arg Lys Ser Asp Ser Ser Pro Tyr
325 330 335Ser Arg Leu Ala Arg Ser Pro Leu Leu Leu Ile Pro Leu Phe Gly Val
340 345 350His Tyr Ile Met Phe Ala Phe Phe Pro Asp Asn Phe Lys Pro Glu Val
355 360 365Lys Met Val Phe Glu Leu Val Val Gly Ser Phe Gln Gly Phe Val Val
370 375 380Ala Ile Leu Tyr Cys Phe Leu Asn Gly Glu Val Gln Ala Glu Leu Arg385 390 395 400Arg Lys Trp Arg Arg Trp His Leu Gln Gly Val Leu Gly Trp Asn Pro
405 410 415Lys Tyr Arg His Pro Ser Gly Gly Ser Asn Gly Ala Thr Cys Ser Thr
420 425 430Gln Val Ser Met Leu Thr Arg Val Ser Pro Gly Ala Arg Arg Ser Ser
435 440 445Ser Phe Gln Ala Glu Val Ser Leu Val
450 455<210>580<211>1317<212>DNA<213>智人(Homo sapiens)<400>580atgcggacgc tgctgcctcc cgcgctgctg acctgctggc tgctcgcccc cgtgaacagc 60attcacccag aatgccgatt tcatctggaa atacaggagg aagaaacaaa atgtacagag 120cttctgaggt ctcaaacaga aaaacacaaa gcctgcagtg gegtctggga caacatcacg 180tgctggcggc ctgccaatgt gggagagacc gtcacggtgc cctgcccaaa agtcttcagc 240aatttttaca gcaaagcagg aaacataagc aaaaactgta cgagtgacgg atggtcagag 300acgttcccag atttcgtcga tgcctgtggc tacagcgacc cggaggatga gagcaagatc 360acgttttata ttctggtgaa ggccatttat accctgggct acagtgtctc tctgatgtct 420cttgcaacag gaagcataat tctgtgcctc ttcaggaagc tgcactgcac caggaattac 480atccacctga acctgttcct gtccttcatc ctgagagcca tctcagtgct ggtcaaggac 540gacgttctct actccagctc tggcacgttg cactgccctg accagccatc ctcctgggtg 600ggctgcaagc tgagcctggt cttcctgcag tactgcatca tggccaactt cttctggctg 660ctggtggagg ggctctacct ccacaccctc ctggtggcca tgctcccccc tagaaggtgc 720ttcctggcct acctcctgat cggatggggc ctccccaccg tctgcatcgg tgcatggact 780gcggccaggc tctacttaga agacaccggt tgctgggata caaacgacca cagtgtgccc 840tggtgggtca tacgaatacc gattttaatt tccatcatcg tcaattttgt ccttttcatt 900agtattatac gaattttgct gcagaagtta acatccccag atgtcggcgg caacgaccag 960tctcagtaca agaggctggc caagtccccg ctcctgctta tcccgctgtt cggcgtccac 1020tacatggtgt ttgccgtgtt tcccatcagc atctcctcca aataccagat actgtttgag 1080ctgtgcctcg ggtcgttcca gggcctggtg gtggccgtcc tctactgttt cctgaacagt 1140gaggtgcagt gcgagctgaa gcgaaaatgg cgaagccggt gcccgacccc gtccgcgagc 1200cgggattaca gggtctgcgg ttcctccttc tcccacaacg gctcggaggg cgccctgcag 1260ttccaccgcg cgtcccgagc ccagtccttc ctgcaaacgg agacctcggt catctag 1317<210>581<211>438<212>PRT<213>智人(Homo sapiens)<400>581Met Arg Thr Leu Leu Pro Pro Ala Leu Leu Thr Cys Trp Leu Leu Ala1 5 10 15Pro Val Asn Ser Ile His Pro Glu Cys Arg Phe His Leu Glu Ile Gln
20 25 30Glu Glu Glu Thr Lys Cys Thr Glu Leu Leu Arg Ser Gln Thr Glu Lys
35 40 45His Lys Ala Cys Ser Gly Val Trp Asp Asn Ile Thr Cys Trp Arg Pro
50 55 60Ala Asn Val Gly Glu Thr Val Thr Val Pro Cys Pro Lys Val Phe Ser65 70 75 80Asn Phe Tyr Ser Lys Ala Gly Asn Ile Ser Lys Asn Cys Thr Ser Asp
85 90 95Gly Trp Ser Glu Thr Phe Pro Asp Phe Val Asp Ala Cys Gly Tyr Ser
100 105 110Asp Pro Glu Asp Glu Ser Lys Ile Thr Phe Tyr Ile Leu Val Lys Ala
115 120 125Ile Tyr Thr Leu Gly Tyr Ser Val Ser Leu Met Ser Leu Ala Thr Gly
130 135 140Ser Ile Ile Leu Cys Leu Phe Arg Lys Leu His Cys Thr Arg Asn Tyr145 150 155 160Ile His Leu Asn Leu Phe Leu Ser Phe Ile Leu Arg Ala Ile Ser Val
165 170 175Leu Val Lys Asp Asp Val Leu Tyr Ser Ser Ser Gly Thr Leu His Cys
180 185 190Pro Asp Gln Pro Ser Ser Trp Val Gly Cys Lys Leu Ser Leu Val Phe
195 200 205Leu Gln Tyr Cys Ile Met Ala Asn Phe Phe Trp Leu Leu Val Glu Gly
210 215 220Leu Tyr Leu His Thr Leu Leu Val Ala Met Leu Pro Pro Arg Arg Cys225 230 235 240Phe Leu Ala Tyr Leu Leu Ile Gly Trp Gly Leu Pro Thr Val Cys Ile
245 250 255Gly Ala Trp Thr Ala Ala Arg Leu Tyr Leu Glu Asp Thr Gly Cys Trp
260 265 270Asp Thr Asn Asp His Ser Val Pro Trp Trp Val Ile Arg Ile Pro Ile
275 280 285Leu Ile Ser Ile Ile Val Asn Phe Val Leu Phe Ile Ser Ile Ile Arg
290 295 300Ile Leu Leu Gln Lys Leu Thr Ser Pro Asp Val Gly Gly Asn Asp Gln305 310 315 320Ser Gln Tyr Lys Arg Leu Ala Lys Ser Pro Leu Leu Leu Ile Pro Leu
325 330 335Phe Gly Val His Tyr Met Val Phe Ala Val Phe Pro Ile Ser Ile Ser
340 345 350Ser Lys Tyr Gln Ile Leu Phe Glu Leu Cys Leu Gly Ser Phe Gln Gly
355 360 365Leu Val Val Ala Val Leu Tyr Cys Phe Leu Asn Ser Glu Val Gln Cys
370 375 380Glu Leu Lys Arg Lys Trp Arg Ser Arg Cys Pro Thr Pro Ser Ala Ser385 390 395 400Arg Asp Tyr Arg Val Cys Gly Ser Ser Phe Ser His Asn Gly Ser Glu
405 410 415Gly Ala Leu Gln Phe His Arg Ala Ser Arg Ala Gln Ser Phe Leu Gln
420 425 430Thr Glu Thr Ser Val Ile
435<210>582<211>32<212>DNA<213>智人(Homo sapiens)<400>582gatctctaga atgaggccgg cggacttgct gc 32<210>583<211>33<212>DNA<213>智人(Homo sapiens)<400>583ctaggatatc cgcaaaaccg tttgcatata ctc 33<210>584<211>30<212>DNA<213>智人(Homo sapiens)<400>584gtgaagcttg cccgggcagg atggacctgg 30<210>585<211>24<212>DNA<213>智人(Homo sapiens)<400>585atctagaggt gcctttgctt tctg 24<210>586<211>3549<212>DNA<213>智人(Homo sapiens)<400>586atgaggccgg cggacttgct gcagctggtg ctgctgctcg acctgcccag ggacctgggc 60ggaatggggt gttcgtctcc accctgcgag tgccatcagg aggaggactt cagagtcacc 120tgcaaggata ttcaacgcat ccccagctta ccgcccagta cgcagactct gaagcttatt 180gagactcacc tgagaactat tccaagtcat gcattttcta atctgcccaa tatttccaga 240atctacgtat ctatagatgt gactctgcag cagctggaat cacactcctt ctacaatttg 300agtaaagtga ctcacataga aattcggaat accaggaact taacttacat agaccctgat 360gccctcaaag agctccccct ectaaagtcc ttggcatttt caaacactgg acttaaaatg 420ttccctgacc tgaccaaagt ttattccact gatatattct ttatacttga aattacagac 480aacccttaca tgaegtcaat ccctgtgaat gcttttcagg gactatgcaa tgaaaccttg 540acactgaagc tgtacaacaa tggctttact tcagtccaag gatatgattt ctttgggaca 600aagctggatg ctgtttacct aaacaagaat aaatacctga cagttattga caaagatgca 660tttggaggag tatacagtgg accaagcttg ctggacgtgt ctcaaaccag tgtcactgcc 720cttccatcca aaggcctgga gcacctgaag gaactgatag caagaaacag ctggactctt 780aagaaacttg cactttcctt gagtttcctt cacctcacac gggctgacct ttcttaccca 840agccactgct gtgcttttaa gaatcagaag aaaatcagag gaatccttga gtccttgatg 900tgtaatgaga gcagtatcga gacgttgcgc cagagaaaat ctgtgaatgc cttgaatagc 960cccctccacc aggaatatga agagaatctg ggtgacagca ttgttgggta caaggaaaag 1020tccaagttcc aggatactca taacaacgct cattattacg tcttctttga agaacaagag 1080gatgagatca ttggttttgg ccaggagctc aaaaaccccc aggaagagac tctacaagct 1140tttgacagcc attatgacta caccatatgt ggggacagtg aagacatggt gtgtaccccc 1200aagtccgatg agttcaaccc gtgtgaagac ataatgggct acaagttcct gagaattgtg 1260gtgtggttcg ttagtctgct ggctctcctg ggcaatgtct ttgtcctgct tattctcctc 1320accagccact acaaactgaa cgtcccccgc tttctcatgt gcaacctggc ctttgcggat 1380ttctgcatgg ggatgtacct gctcctcatc gcctctgtag acctctacac tcactctgag 1440tactacaacc atgccatcga ctggcagaca ggccctgggt gcaacacggc tggtttcttc 1500actgtctttg caagcgagtt atcggtgtat acgctgacgg tcatcaccct ggagcgctgg 1560tatgccatca ccttcgccat ggccctggac cggaagatcc gcctcaggca cgcatgtgcc 1620atcatggttg ggggctgggt ttgctgcttc cttctcgccc tgcttccttt ggtgggaata 1680agtagctatg ccaaagtcag tatctgcctg cccatggaca ccgagacccc tcttgctctg 1740gcatatattg tttttgttct gacgctcaac atagttgcct tcgtcatcgt ctgctgctgt 1800tatgtgaaga tctacatcac agtccgaaat ccgcagtaca acccagggga caaagatacc 1860aaaattaaga agaggatggc tgtgttgatc ttcaccgact tcacgtgcat ggccccaatc 1920tcattctatg ctgtgtcagc aattctgaac aagcctctca tcactgttag caactccaaa 1980atcttgctgg tactcttcta tccaattaac tcctgtgcca atccattcct ctatgctatt 2040ttcaccaagg ccttccagag ggatgtgttc atcctactca gcaagtttgg catctgtaaa 2100cgccaggctc aggcataccg ggggcagagg gttcctccaa agaacagcac tgatattcag 2160gttcaaaagg ttacccacga catgaggcag ggtctccaca acatggaaga tgtctatgaa 2220ctgattgaaa actcccatct aaccccaaag aagcaaggcc aaatctcaga agagtatatg 2280caaacggttt tggcgatatc tgcagaattc caccacactg gactagtgga tccgagctcg 2340gtaccaagct tgggctgcag gtcgatgggc tgcctcggca acagtaagac cgaggaccag 2400cgcaacgagg agaaggcgca gcgcgaggcc aacaaaaaga tcgagaagca gctgcagaag 2460gacaagcagg tctaccgggc cacgcaccgc ctgctgctgc tgggtgctgg agagtctggc 2520aaaagcacca ttgtgaagca gatgaggatc ctacatgtta atgggtttaa cggagagggc 2580ggcgaagagg acccgcaggc tgcaaggagc aacagcgatg gtgagaaggc caccaaagtg 2640caggacatca aaaacaacct gaaggaggcc attgaaacca ttgtggccgc catgagcaac 2700ctggtgcccc ccgtggagct ggccaaccct gagaaccagt tcagagtgga ctacattctg 2760agcgtgatga acgtgccaaa ctttgacttc ccacctgaat tctatgagca tgccaaggct 2820ctgtgggagg atgagggagt tcgtgcctgc tacgagcgct ccaacgagta ccagctgatc 2880gactgtgccc agtacttcct ggacaagatt gatgtgatca agcaggccga ctacgtgcca 2940agtgaccagg acctgcttcg ctgccgcgtc ctgacctctg gaatctttga gaccaagttc 3000caggtggaca aagtcaactt ccacatgttc gatgtgggcg gccagcgcga tgaacgccgc 3060aagtggatcc agtgcttcaa tgatgtgact gccatcatct tcgtggtggc cagcagcagc 3120tacaacatgg tcatccggga ggacaaccag accaaccgtc tgcaggaggc tctgaacctc 3180ttcaagagca tctggaacaa cagatggctg cgtaccatct ctgtgatcct cttcctcaac 3240aagcaagatc tgcttgctga gaaggtcctc gctgggaaat cgaagattga ggactacttt 3300ccagagttcg ctcgctacac cactcctgag gatgcgactc ccgagcccgg agaggaccca 3360cgcgtgaccc gggccaagta cttcatccgg gatgagtttc tgagaatcag cactgctagt 3420ggagatggac gtcactactg ctaccctcac tttacctgcg ccgtggacac tgagaacatc 3480cgccgtgtct tcaacgactg ccgtgacatc atccagcgca tgcatcttcg ccaatacgag 3540ctgctctaa 3549<210>587<21l>1181<212>PRT<213>智人(Homo sapiens)<400>587Met Arg Pro Ala Asp Leu Leu Gln Leu Val Leu Leu Leu Asp Leu Pro1 5 10 15Arg Asp Leu Gly Gly Met Gly Cys Ser Ser Pro Pro Cys Glu Cys His
20 25 30Gln Glu Glu Asp Phe Arg Val Thr Cys Lys Asp Ile Gln Arg Ile Pro
35 40 45Ser Leu Pro Pro Ser Thr Gln Thr Leu Lys Leu Ile Glu Thr His Leu
50 55 60Arg Thr Ile Pro Ser His Ala Phe Ser Asn Leu Pro Asn Ile Ser Arg65 70 75 80Ile Tyr Val Ser Ile Asp Val Thr Leu Gln Gln Leu Glu Ser His Ser
85 90 95Phe Tyr Asn Leu Ser Lys Val Thr His Ile Glu Ile Arg Asn Thr Arg
100 105 110Asn Leu Thr Tyr Ile Asp Pro Asp Ala Leu Lys Glu Leu Pro Leu Leu
115 120 125Lys Ser Leu Ala Phe Ser Asn Thr Gly Leu Lys Met Phe Pro Asp Leu
130 135 140Thr Lys Val Tyr Ser Thr Asp Ile Phe Phe Ile Leu Glu Ile Thr Asp145 150 155 160Asn Pro Tyr Met Thr Ser Ile Pro Val Asn Ala Phe Gln Gly Leu Cys
165 170 175Asn Glu Thr Leu Thr Leu Lys Leu Tyr Asn Asn Gly Phe Thr Ser Val
180 185 190Gln Gly Tyr Asp Phe Phe Gly Thr Lys Leu Asp Ala Val Tyr Leu Asn
195 200 205Lys Asn Lys Tyr Leu Thr Val Ile Asp Lys Asp Ala Phe Gly Gly Val
210 215 220Tyr Ser Gly Pro Ser Leu Leu Asp Val Ser Gln Thr Ser Val Thr Ala225 230 235 240Leu Pro Ser Lys Gly Leu Glu His Leu Lys Glu Leu Ile Ala Arg Asn
245 250 255Ser Trp Thr Leu Lys Lys Leu Ala Leu Ser Leu Ser Phe Leu His Leu
260 265 270Thr Arg Ala Asp Leu Ser Tyr Pro Ser His Cys Cys Ala Phe Lys Asn
275 280 285Gln Lys Lys Ile Arg Gly Ile Leu Glu Ser Leu Met Cys Asn Glu Ser
290 295 300Ser Ile Glu Thr Leu Arg Gln Arg Lys Ser Val Asn Ala Leu Asn Ser305 310 315 320Pro Leu His Gln Glu Tyr Glu Glu Asn Leu Gly Asp Ser Ile Val Gly
325 330 335Tyr Lys Glu Lys Ser Lys Phe Gln Asp Thr His Asn Asn Ala His Tyr
340 345 350Tyr Val Phe Phe Glu Glu Gln Glu Asp Glu Ile Ile Gly Phe Gly Gln
355 360 365Glu Leu Lys Asn Pro Gln Glu Glu Thr Leu Gln Ala Phe Asp Ser His
370 375 380Tyr Asp Tyr Thr Ile Cys Gly Asp Ser Glu Asp Met Val Cys Thr Pro385 390 395 400Lys Ser Asp Glu Phe Asn Pro Cys Glu Asp Ile Met Gly Tyr Lys Phe
405 410 415Leu Arg Ile Val Val Trp Phe Val Ser Leu Leu Ala Leu Leu Gly Asn
420 425 430Val Phe Val Leu Leu Ile Leu Leu Thr Ser His Tyr Lys Leu Asn Val
435 440 445Pro Arg Phe Leu Met Cys Asn Leu Ala Phe Ala Asp Phe Cys Met Gly
450 455 460Met Tyr Leu Leu Leu Ile Ala Ser Val Asp Leu Tyr Thr His Ser Glu465 470 475 480Tyr Tyr Asn His Ala Ile Asp Trp Gln Thr Gly Pro Gly Cys Asn Thr
485 490 495Ala Gly Phe Phe Thr Val Phe Ala Ser Glu Leu Ser Val Tyr Thr Leu
500 505 510Thr Val Ile Thr Leu Glu Arg Trp Tyr Ala Ile Thr Phe Ala Met Ala
515 520 525Leu Asp Arg Lys Ile Arg Leu Arg His Ala Cys Ala Ile Met Val Gly
530 535 540Gly Trp Val Cys Cys Phe Leu Leu Ala Leu Leu Pro Leu Val Gly Ile545 550 555 560Ser Ser Tyr Ala Lys Val Ser Ile Cys Leu Pro Met Asp Thr Glu Thr
565 570 575Pro Leu Ala Leu Ala Tyr Ile Val Phe Val Leu Thr Leu Asn Ile Val
580 585 590Ala Phe Val Ile Val Cys Cys Cys Tyr Val Lys Ile Tyr Ile Thr Val
595 600 605Arg Asn Pro His Asn Pro Gly Asp Lys Asp Thr Lys Ile Ala Lys Arg
610 615 620Met Ala Val Leu Ile Phe Thr Asp Phe Thr Cys Met Ala Pro Ile Ser625 630 635 640Phe Tyr Ala Val Ser Ala Ile Leu Asn Lys Pro Leu Ile Thr Val Ser
645 650 655Asn Ser Lys Ile Leu Leu Val Leu Phe Tyr Pro Ile Asn Ser Cys Ala
660 665 670Asn Pro Phe Leu Tyr Ala Ile Phe Thr Lys Ala Phe Gln Arg Asp Val
675 680 685Phe Ile Leu Leu Ser Lys Phe Gly Ile Cys Lys Arg Gln Ala Gln Ala
690 695 700Tyr Arg Gly Gln Arg Val Pro Pro Lys Asn Ser Thr Asp Ile Gln Val705 710 715 720Gln Lys Val Thr His Asp Met Arg Gln Gly Leu His Asn Met Glu Asp
725 730 735Val Tyr Glu Leu Ile Glu Asn Ser His Leu Thr Pro Lys Lys Gln Gly
740 745 750Gln Ile Ser Glu Glu Tyr Met Gln Thr Val Leu Ala Ile Ser Ala Glu
755 760 765Phe His His Thr Gly Leu Val Asp Pro Ser Ser Val Pro Ser Leu Gly
770 775 780Cys Arg Ser Met Gly Cys Leu Gly Asn Ser Lys Thr Glu Asp Gln Arg785 790 795 800Asn Glu Glu Lys Ala Gln Arg Glu Ala Asn Lys Lys Ile Glu Lys Gln
805 810 815Leu Gln Lys Asp Lys Gln Val Tyr Arg Ala Thr His Arg Leu Leu Leu
820 825 830Leu Gly Ala Gly Glu Ser Gly Lys Ser Thr Ile Val Lys Gln Met Arg
835 840 845Ile Leu His Val Asn Gly Phe Asn Gly Glu Gly Gly Glu Glu Asp Pro
850 855 860Gln Ala Ala Arg Ser Asn Ser Asp Gly Glu Lys Ala Thr Lys Val Gln865 870 875 880Asp Ile Lys Asn Asn Leu Lys Glu Ala Ile Glu Thr Ile Val Ala Ala
885 890 895Met Ser Asn Leu Val Pro Pro Val Glu Leu Ala Asn Pro Glu Asn Gln
900 905 910Phe Arg Val Asp Tyr Ile Leu Ser Val Met Asn Val Pro Asn Phe Asp
915 920 925Phe Pro Pro Glu Phe Tyr Glu His Ala Lys Ala Leu Trp Glu Asp Glu
930 935 940Gly Val Arg Ala Cys Tyr Glu Arg Ser Asn Glu Tyr Gln Leu Ile Asp945 950 955 960Cys Ala Gln Tyr Phe Leu Asp Lys Ile Asp Val Ile Lys Gln Ala Asp
965 970 975Tyr Val Pro Ser Asp Gln Asp Leu Leu Arg Cys Arg Val Leu Thr Ser
980 985 990Gly Ile Phe Glu Thr Lys Phe Gln Val Asp Lys Val Asn Phe His Met
995 1000 1005Phe Asp Val Gly Gly Gln Arg Asp Glu Arg Arg Lys Trp Ile Gln
1010 1015 1020Cys Phe Asn Asp Val Thr Ala Ile Ile Phe Val Val Ala Ser Ser
1025 1030 1035Ser Tyr Asn Met Val Ile Arg Glu Asp Asn Gln Thr Asn Arg Leu
1040 1045 1050Gln Glu Ala Leu Asn Leu Phe Lys Ser Ile Trp Asn Asn Arg Trp
1055 1060 1065Leu Arg Thr Ile Ser Val Ile Leu Phe Leu Asn Lys Gln Asp Leu
1070 1075 1080Leu Ala Glu Lys Val Leu Ala Gly Lys Ser Lys Ile Glu Asp Tyr
1085 1090 1095Phe Pro Glu Phe Ala Arg Tyr Thr Thr Pro Glu Asp Ala Thr Pro
1100 1105 1110Glu Pro Gly Glu Asp Pro Arg Val Thr Arg Ala Lys Tyr Phe Ile
1115 1120 1125Arg Asp Glu Phe Leu Arg Ile Ser Thr Ala Ser Gly Asp Gly Arg
1130 1135 1140His Tyr Cys Tyr Pro His Phe Thr Cys Ala Val Asp Thr Glu Asn
1145 1150 1155Ile Arg Arg Val Phe Asn Asp Cys Arg Asp Ile Ile Gln Arg Met
1160 1165 1170His Leu Arg Gln Tyr Glu Leu Leu
1175 1180<210>588<211>2133<212>DNA<213>智人(Homo sapiens)<400>588atggacctgg aagcctcgct gctgcccact ggtcccaatg ccagcaacac ctctgatggc 60cccgataacc tcacttcggc aggatcacct cctcgcacgg ggagcatctc ctacatcaac 120atcatcatgc cttcggtgtt cggcaccatc tgcctcctgg gcatcatcgg gaactccacg 180gtcatcttcg cggtcgtgaa gaagtccaag ctgcactggt gcaacaacgt ccccgacatc 240ttcatcatca acctctcggt agtagatctc ctctttctcc tgggcatgcc cttcatgatc 300caccagctca tgggcaatgg ggtgtggcac tttggggaga ccatgtgcac cctcatcacg 360gccatggatg ccaatagtca gttcaccagc acctacatcc tgaccgccat ggccattgac 420cgctacctgg ccactgtcca ccccatctct tccacgaagt tccggaagcc ctctgtggcc 480accctggtga tctgcctcct gtgggccctc tccttcatca gcatcacccc tgtgtggctg 540tatgccagac tcatcccctt cccaggaggt gcagtgggct gcggcatacg cctgcccaac 600ccagacactg acctctactg gttcaccctg taccagtttt tcctggcctt tgccctgcct 660tttgtggtca tcacagccgc atacgtgagg atcctgcagc gcatgacgtc ctcagtggcc 720cccgcctccc agcgcagcat ccggctgcgg acaaagaggg tgacccgcac agccatcgcc 780atctgtctgg tcttctttgt gtgctgggca ccctactatg tgctacagct gacccagttg 840tccatcagcc gcccgaccct cacctttgtc tacttataca atgcggccat cagcttgggc 900tatgccaaca gctgcctcaa cccctttgtg tacatcgtgc tctgtgagac gttccgcaaa 960cgcttggtcc tgtcggtgaa gcctgcagcc caggggcagc ttcgcgctgt cagcaacgct 1020cagacggctg acgaggagag gacagaaagc aaaggcacct ctagaatggg ctgcacactg 1080agcgctgagg acaaggcggc cgtggagcgc agcaagatga tcgaccgcaa cctccgggag 1140gacggagaga aggcagcgcg cgaggtcaag ctgctgctgc tgggtgctgg tgaatccggg 1200aagagcacaa ttgtgaagca gatgaaaatt atccacgagg ctggctactc agaggaagag 1260tgtaagcagt acaaagcagt ggtctacagc aacaccatcc agtccatcat tgccatcatt 1320agagccatgg ggagattgaa aatcgacttt ggagacgctg ctcgtgcgga tgatgctcgc 1380caactcttcg tgcttgctgg ggctgcagag gaaggcttta tgaccgcgga gctcgccggc 1440gtcataaaga gactgtggaa ggacagcggt gtgcaagcct gcttcaacag atcccgggag 1500taccagctga acgattcggc ggcgtactac ctgaatgact tggacagaat agcacaacca 1560aattacatcc caacccagca ggatgttctc agaactagag tgaaaacgac gggaattgtg 1620gaaacccact ttactttcaa agatcttcat tttaaaatgt ttgacgtggg aggccagaga 1680tcagagcgga agaagtggat tcactgcttt gaaggcgtga ctgccatcat cttctgtgtg 1740gccctgagtg actatgacct ggttcttgct gaggatgaag aaatgaaccg gatgcatgaa 1800agcatgaagc tgttcgatag catatgtaac aacaagtggt ttacggacac atccatcatc 1860cttttcctga acaagaagga cctcttcgaa gagaagatca aaaagagtcc cctcacgata 1920tgctatccag aatatgcagg ctcaaacaca tatgaagagg cggctgcgta tatccagtgt 1980cagtttgaag acctcaataa aaggaaggac acaaaggaaa tttacaccca cttcacttgc 2040gccacggata cgaagaatgt gcagtttgtg ttcgatgctg taacggacgt catcataaag 2100aataacctaa aagactgtgg tctcttctaa tct 2133<210>589<211>709<212>PRT<213>智人(Homo sapiens)<400>589Met Asp Leu Glu Ala Ser Leu Leu Pro Thr Gly Pro Asn Ala Ser Asn1 5 10 15Thr Ser Asp Gly Pro Asp Asn Leu Thr Ser Ala Gly Ser Pro Pro Arg
20 25 30Thr Gly Ser Ile Ser Tyr Ile Asn Ile Ile Met Pro Ser Val Phe Gly
35 40 45Thr Ile Cys Leu Leu Gly Ile Ile Gly Asn Ser Thr Val Ile Phe Ala
50 55 60Val Val Lys Lys Ser Lys Leu His Trp Cys Asn Asn Val Pro Asp Ile65 70 75 80Phe Ile Ile Asn Leu Ser Val Val Asp Leu Leu Phe Leu Leu Gly Met
85 90 95Pro Phe Met Ile His Gln Leu Met Gly Asn Gly Val Trp His Phe Gly
100 105 110Glu Thr Met Cys Thr Leu Ile Thr Ala Met Asp Ala Asn Ser Gln Phe
115 120 125Thr Ser Thr Tyr Ile Leu Thr Ala Met Ala Ile Asp Arg Tyr Leu Ala
130 135 140Thr Val His Pro Ile Ser Ser Thr Lys Phe Arg Lys Pro Ser Val Ala145 150 155 160Thr Leu Val Ile Cys Leu Leu Trp Ala Leu Ser Phe Ile Ser Ile Thr
165 170 175Pro Val Trp Leu Tyr Ala Arg Leu Ile Pro Phe Pro Gly Gly Ala Val
180 185 190Gly Cys Gly Ile Arg Leu Pro Asn Pro Asp Thr Asp Leu Tyr Trp Phe
195 200 205Thr Leu Tyr Gln Phe Phe Leu Ala Phe Ala Leu Pro Phe Val Val Ile
210 215 220Thr Ala Ala Tyr Val Arg Ile Leu Gln Arg Met Thr Ser Ser Val Ala225 230 235 240Pro Ala Ser Gln Arg Ser Ile Arg Leu Arg Thr Lys Arg Val Thr Arg
245 250 255Thr Ala Ile Ala Ile Cys Leu Val Phe Phe Val Cys Trp Ala Pro Tyr
260 265 270Tyr Val Leu Gln Leu Thr Gln Leu Ser Ile Ser Arg Pro Thr Leu Thr
275 280 285Phe Val Tyr Leu Tyr Asn Ala Ala Ile Ser Leu Gly Tyr Ala Asn Ser
290 295 300Cys Leu Asn Pro Phe Val Tyr Ile Val Leu Cys Glu Thr Phe Arg Lys305 310 315 320Arg Leu Val Leu Ser Val Lys Pro Ala Ala Gln Gly Gln Leu Arg Ala
325 330 335Val Ser Asn Ala Gln Thr Ala Asp Glu Glu Arg Thr Glu Ser Lys Gly
340 345 350Thr Ser Arg Met Gly Cys Thr Leu Ser Ala Glu Asp Lys Ala Ala Val
355 360 365Glu Arg Ser Lys Met Ile Asp Arg Asn Leu Arg Glu Asp Gly Glu Lys
370 375 380Ala Ala Arg Glu Val Lys Leu Leu Leu Leu Gly Ala Gly Glu Ser Gly385 390 395 400Lys Ser Thr Ile Val Lys Gln Met Lys Ile Ile His Glu Ala Gly Tyr
405 410 415Ser Glu Glu Glu Cys Lys Gln Tyr Lys Ala Val Val Tyr Ser Asn Thr
420 425 430Ile Gln Ser Ile Ile Ala Ile Ile Arg Ala Met Gly Arg Leu Lys Ile
435 440 445Asp Phe Gly Asp Ala Ala Arg Ala Asp Asp Ala Arg Gln Leu Phe Val
450 455 460Leu Ala Gly Ala Ala Glu Glu Gly Phe Met Thr Ala Glu Leu Ala Gly465 470 475 480Val Ile Lys Arg Leu Trp Lys Asp Ser Gly Val Gln Ala Cys Phe Asn
485 490 495Arg Ser Arg Glu Tyr Gln Leu Asn Asp Ser Ala Ala Tyr Tyr Leu Asn
500 505 510Asp Leu Asp Arg Ile Ala Gln Pro Asn Tyr Ile Pro Thr Gln Gln Asp
515 520 525Val Leu Arg Thr Arg Val Lys Thr Thr Gly Ile Val Glu Thr His Phe
530 535 540Thr Phe Lys Asp Leu His Phe Lys Met Phe Asp Val Gly Gly Gln Arg545 550 555 560Ser Glu Arg Lys Lys Trp Ile His Cys Phe Glu Gly Val Thr Ala Ile
565 570 575Ile Phe Cys Val Ala Leu Ser Asp Tyr Asp Leu Val Leu Ala Glu Asp
580 585 590Glu Glu Met Asn Arg Met His Glu Ser Met Lys Leu Phe Asp Ser Ile
595 600 605Cys Asn Asn Lys Trp Phe Thr Asp Thr Ser Ile Ile Leu Phe Leu Asn
610 615 620Lys Lys Asp Leu Phe Glu Glu Lys Ile Lys Lys Ser Pro Leu Thr Ile625 630 635 640Cys Tyr Pro Glu Tyr Ala Gly Ser Asn Thr Tyr Glu Glu Ala Ala Ala
645 650 655Tyr Ile Gln Cys Gln Phe Glu Asp Leu Asn Lys Arg Lys Asp Thr Lys
660 665 670Glu Ile Tyr Thr His Phe Thr Cys Ala Thr Asp Thr Lys Asn Val Gln
675 680 685Phe Val Phe Asp Ala Val Thr Asp Val Ile Ile Lys Asn Asn Leu Lys
690 695 700Asp Cys Gly Leu Phe705
Claims (102)
1.一种直接识别非内源化合物的方法,该化合物具有选自针对非内源性组成型活化的已知G蛋白偶联受体变体的反激动剂,部分激动剂和激动剂活性的化合物,所述受体包含跨膜-6区域和细胞内区域,所述方法包括以下步骤:
(a)选择具有特定氨基酸序列的已知GPCR的非内源形式,所述氨基酸序列选自:SEQ.ID.NO.:425;SEQ.ID.NO.:427;SEQ.ID.NO.:429;SEQ.ID.NO.:431;SEQ.ID.NO.:433;SEQ.ID.NO.:435;SEQ.ID.NO.:437;SEQ.ID.NO.:439;SEQ.ID.NO.:441;SEQ.ID.NO.:443;SEQ.ID.NO.:445;SEQ.ID.NO.:447;SEQ.ID.NO.:449;SEQ.ID.NO.:451;SEQ.ID.NO.:453;SEQ.ID.NO.:455;SEQ.ID.NO.:457;SEQ.ID.NO.:459;SEQ.ID.NO.:461;SEQ.ID.NO.:463;SEQ.ID.NO.:465;SEQ.ID.NO.:467;SEQ.ID.NO.:469;SEQ.ID.NO.:471;SEQ.ID.NO.:473;SEQ.ID.NO.:475;SEQ.ID.NO.:477;SEQ.ID.NO.:479;SEQ.ID.NO.:481;SEQ.ID.NO.:483;SEQ.ID.NO.:485;SEQ.ID.NO.:487;SEQ.ID.NO.:489;SEQ.ID.NO.:491;SEQ.ID.NO.:493;SEQ.ID.NO.:495;SEQ.ID.NO.:497;SEQ.ID.NO.:499;SEQ.ID.NO.:501;SEQ.ID.NO.:503;SEQ.ID.NO.:505;SEQ.ID.NO.:507;SEQ.ID.NO.:347;SEQ.ID.NO.:509;SEQ.ID.NO.:351;SEQ.ID.NO.:355;SEQ.ID.NO.:359;SEQ.ID.NO.:363;SEQ.ID.NO.:367;SEQ.ID.NO.:371;SEQ.ID.NO.:375;SEQ.ID.NO.:379;SEQ.ID.NO.:383;SEQ.ID.NO.:387;SEQ.ID.NO.:391;SEQ.ID.NO.:511;SEQ.ID.NO.:513;SEQ.ID.NO.:515;SEQ.ID.NO.:517;SEQ.ID.NO.:519;SEQ.ID.NO.:521;SEQ.ID.NO.:523;SEQ.ID.NO.:525;SEQ.ID.NO.:527;SEQ.ID.NO.:529;SEQ.ID.NO.:531;SEQ.ID.NO.:533;SEQ.ID.NO.:535;SEQ.ID.NO.:537;SEQ.ID.NO.:539;SEQ.ID.NO.:541;SEQ.ID.NO.:543;SEQ.ID.NO.:545;SEQ.ID.NO.:547;SEQ.ID.NO.:549;SEQ.ID.NO.:551;SEQ.ID.NO.:553;SEQ.ID.NO.:555;SEQ.ID.NO.:557;SEQ.ID.NO.:559;SEQ.ID.NO.:561;SEQ.ID.NO.:563;SEQ.ID.NO.:565;SEQ.ID.NO.:567;SEQ.ID.NO.:569;SEQ.ID.NO.:571;SEQ.ID.NO.:573;SEQ.ID.NO.:575;SEQ.ID.NO.:577;SEQ.ID.NO.:395;SEQ.ID.NO.:399;SEQ.ID.NO.:403;SEQ.ID.NO.:407;SEQ.ID.NO.:411;SEQ.ID.NO.:415;SEQ.ID.NO.:419;SEQ.ID.NO.:423;SEQ.ID.NO.:579和SEQ.ID.NO.:581;
(b)确认步骤(a)所选择的非内源性GPCR是组成型活化的;
(c)将非内源侯选化合物与步骤(b)的非内源性组成型活化的GPCR接触;和
(d)通过检测该化合物对于所接触受体的效率,确定作为反激动剂具有反激动剂活性或具有激动剂活性的所述非内源化合物是否是步骤(b)中所述受体的激动剂。
2.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:425序列的氨基酸序列。
3.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:427序列的氨基酸序列。
4.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:429序列的氨基酸序列。
5.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:431序列的氨基酸序列。
6.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:433序列的氨基酸序列。
7.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:435序列的氨基酸序列。
8.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:437序列的氨基酸序列。
9.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:439序列的氨基酸序列。
10.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:441序列的氨基酸序列。
11.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:443序列的氨基酸序列。
12.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:445序列的氨基酸序列。
13.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:447序列的氨基酸序列。
14.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:449序列的氨基酸序列。
15.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:451序列的氨基酸序列。
16.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:453序列的氨基酸序列。
17.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:455序列的氨基酸序列。
18.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:457序列的氨基酸序列。
19.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:459序列的氨基酸序列。
20.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:461序列的氨基酸序列。
21.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:463序列的氨基酸序列。
22.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:465序列的氨基酸序列。
23.权利要求1的方法,其中该非内源性GPCR是467。
24.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:469序列的氨基酸序列。
25.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:471序列的氨基酸序列。
26.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:473序列的氨基酸序列。
27.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:475序列的氨基酸序列。
28.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:477序列的氨基酸序列。
29.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:479序列的氨基酸序列。
30.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:481序列的氨基酸序列。
31.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:483序列的氨基酸序列。
32.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:485序列的氨基酸序列。
33.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:487序列的氨基酸序列。
34.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:489序列的氨基酸序列。
35.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:491序列的氨基酸序列。
36.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:493序列的氨基酸序列。
37.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:495序列的氨基酸序列。
38.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:497序列的氨基酸序列。
39.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:499序列的氨基酸序列。
40.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:501序列的氨基酸序列。
41.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:503序列的氨基酸序列。
42.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:505序列的氨基酸序列。
43.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:507序列的氨基酸序列。
44.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:347序列的氨基酸序列。
45.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:509序列的氨基酸序列。
46.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:351序列的氨基酸序列。
47.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:355序列的氨基酸序列。
48.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:359序列的氨基酸序列。
49.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:361序列的氨基酸序列。
50.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:367序列的氨基酸序列。
51.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:371序列的氨基酸序列。
52.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:375序列的氨基酸序列。
53.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:379序列的氨基酸序列。
54.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:383序列的氨基酸序列。
55.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:387序列的氨基酸序列。
56.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:391序列的氨基酸序列。
57.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:511序列的氨基酸序列。
58.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:513序列的氨基酸序列。
59.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:515序列的氨基酸序列。
60.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:517序列的氨基酸序列。
61.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:519序列的氨基酸序列。
62.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:521序列的氨基酸序列。
63.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:523序列的氨基酸序列。
64.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:525序列的氨基酸序列。
65.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:527序列的氨基酸序列。
66.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:529序列的氨基酸序列。
67.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:531序列的氨基酸序列。
68.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:533序列的氨基酸序列。
69.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:535序列的氨基酸序列。
70.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:537序列的氨基酸序列。
71.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:539序列的氨基酸序列。
72.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:541序列的氨基酸序列。
73.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:543序列的氨基酸序列。
74.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:545序列的氨基酸序列。
75.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:547序列的氨基酸序列。
76.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:549序列的氨基酸序列。
77.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:551序列的氨基酸序列。
78.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:553序列的氨基酸序列。
79.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:555序列的氨基酸序列。
80.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:557序列的氨基酸序列。
81.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:559序列的氨基酸序列。
82.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:561序列的氨基酸序列。
83.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:563序列的氨基酸序列。
84.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:565序列的氨基酸序列。
85.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:567序列的氨基酸序列。
86.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:569序列的氨基酸序列。
87.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:571序列的氨基酸序列。
88.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:573序列的氨基酸序列。
89.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:575序列的氨基酸序列。
90.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:577序列的氨基酸序列。
91.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:395序列的氨基酸序列。
92.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:399序列的氨基酸序列。
93.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:403序列的氨基酸序列。
94.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:407序列的氨基酸序列。
95.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:411序列的氨基酸序列。
96.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:415序列的氨基酸序列。
97.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:419序列的氨基酸序列。
98.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:423序列的氨基酸序列。
99.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:579序列的氨基酸序列。
100.权利要求1的方法,其中该步骤(b)中的非内源性GPCR是具有SEQ.ID.NO.:581序列的氨基酸序列。
101.权利要求1的方法,其进一步包含以下步骤:通过使用基于内源配体的实验,评估步骤(b)中非内源化合物对于步骤(a)中所述已知GPCR的非内源形式的已知GPCR的内源配体形式与所述已知GPCR结合的影响。
102.权利要求101的方法,其中所述非内源化合物是所述已知GPCR的一种别构调节剂。
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| CA2164966A1 (en) * | 1993-06-23 | 1995-01-05 | Wolfgang Sadee | Compositions and methods for anti-addictive narcotic analgesis activity screening and treatments |
| US5882944A (en) * | 1993-06-23 | 1999-03-16 | The Regents Of The University Of California | Methods for G protein coupled receptor activity screening |
| US6087115A (en) | 1997-01-22 | 2000-07-11 | Cornell Research Foundation, Inc. | Methods of identifying negative antagonists for G protein coupled receptors |
| AU6343998A (en) * | 1997-02-27 | 1998-09-18 | Christina C. Egan | Constitutively activated serotonin receptors |
| US6107324A (en) * | 1998-04-14 | 2000-08-22 | Arena Pharmaceuticals Inc. | 5-HT2A receptor inverse agonists |
| US6140509A (en) * | 1998-06-26 | 2000-10-31 | Arena Pharmaceuticals, Inc. | Non-endogenous, constitutively activated human serotonin receptors and small molecule modulators thereof |
| AU751080B2 (en) * | 1998-07-31 | 2002-08-08 | Arena Pharmaceuticals, Inc. | Endogenous constitutively activated G protein-coupled orphan receptors |
| US6358698B1 (en) * | 1998-10-07 | 2002-03-19 | Acadia Pharmacueticals Inc. | Methods of identifying inverse agonists of the serotonin 2A receptor |
| US6150393A (en) * | 1998-12-18 | 2000-11-21 | Arena Pharmaceuticals, Inc. | Small molecule modulators of non-endogenous, constitutively activated human serotonin receptors |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102276731A (zh) * | 2011-08-16 | 2011-12-14 | 北京大学 | 抑制可卡因诱发的高运动活性的多肽及其应用 |
| CN102276731B (zh) * | 2011-08-16 | 2013-03-27 | 北京大学 | 抑制可卡因诱发的高运动活性的多肽及其应用 |
| CN118406133A (zh) * | 2024-05-30 | 2024-07-30 | 徐州医科大学 | 一种多肽5-HT4R-peptide及其应用 |
| CN118406133B (zh) * | 2024-05-30 | 2025-02-28 | 徐州医科大学 | 一种多肽5-HT4R-peptide及其应用 |
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| CA2402392A1 (en) | 2001-10-18 |
| US20050019840A1 (en) | 2005-01-27 |
| WO2001077172A2 (en) | 2001-10-18 |
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| US7097969B2 (en) | 2006-08-29 |
| IL152136A0 (en) | 2003-05-29 |
| WO2001077172A3 (en) | 2003-01-30 |
| US20060183164A1 (en) | 2006-08-17 |
| AU2001249885A1 (en) | 2001-10-23 |
| US20030204073A1 (en) | 2003-10-30 |
| US7381522B2 (en) | 2008-06-03 |
| MXPA02009902A (es) | 2003-06-17 |
| EP1301594A2 (en) | 2003-04-16 |
| NZ521158A (en) | 2004-08-27 |
| JP2003532057A (ja) | 2003-10-28 |
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