人受体蛋白；相关的试剂和方法

专利名称：人受体蛋白；相关的试剂和方法
技术领域：
本发明涉及一些组合物及方法，用于影响哺乳动物的生理机能，包括形态发生或免疫系统功能。详细地说，本发明提供一些能够调节发育和/或免疫系统的核酸、蛋白及抗体。此外还公开这些物质的诊断性和治疗性应用。
背景技术：
DNA重组技术通常是指把来自源供体的遗传信息整合到载体中用于后续处理，如引入到宿主中，从而在新环境下复制和/或表达被转移的遗传信息的技术。这些遗传信息通常是以互补DNA(cDNA)的形式存在，这些cDNA来源于编码所需蛋白产物的信使RNA(mRNA)。载体通常是一种质粒，这种质粒能够整合cDNA，并随后在宿主中复制，在某些情况下还能够调控cDNA的表达，从而指导其编码产物在宿主中的合成。
此前已认识到哺乳动物免疫应答的基础是一系列复杂的细胞间相互作用，被称为“免疫网络”。近期的研究则使人们对该网络的内部工作方式有了新的理解。事实上，许多免疫应答都围绕着淋巴细胞、巨噬细胞、粒细胞和其他细胞之间的网状相互作用而产生，尽管对此还不完全了解，但免疫学家目前的普遍观点是，被称为淋巴因子、细胞因子或单核因子的可溶性蛋白在对这些细胞间相互作用的调控过程中发挥着关键的作用。因此，分离和鉴定细胞调节因子并研究其作用机理是一大热点，对这些知识的了解有助于显著改进免疫系统失调等众多医学异常疾病的诊断和治疗方法。
显然，淋巴因子可通过多种方式来调节细胞的活动。研究显示，这些淋巴因子可支持多能造血干细胞的增殖、生长和/或分化成大量祖细胞，这些祖细胞包括不同的细胞谱系，从而构成复杂的免疫系统。对正常的免疫应答而言，这些细胞组分之间的相互作用必须适当，并且要保持平衡。将淋巴因子与其他试剂一同给药时，不同的细胞谱系通常以不同的方式产生应答。
对免疫应答尤为重要的细胞谱系包括两类淋巴细胞产生和分泌免疫球蛋白(能够识别并结合异物从而实现其清除作用的蛋白)的B细胞，以及分泌淋巴因子并诱导或抑制B细胞和构成免疫网络的其他多种细胞(包括其他T细胞)的不同的T细胞亚类。这些淋巴细胞可与其他多种类型的细胞相互作用。
另一种重要的细胞谱系是肥大细胞(目前还未能在所有种类的哺乳动物中明确鉴定出此类细胞)，它是一种位于全身毛细血管附近的含有颗粒的结缔组织细胞。此类细胞在肺、皮肤以及胃肠道和泌尿生殖道中出现的浓度特别高。肥大细胞在变态反应相关性病症中起主要作用，尤其是在下述过敏反应中当特定抗原与结合在肥大细胞表面受体上的一类免疫球蛋白交联时，该肥大细胞可脱粒并释放介体，如组胺、5羟色胺、肝素和前列腺素，从而导致变态反应，如过敏反应。
一般而言，目前还无法在体外培养免疫系统细胞，这使进一步了解并治疗多种免疫功能障碍的研究受阻。免疫学家发现，利用T细胞及其他细胞的上清液可以对多种免疫系统细胞进行培养，这些上清液含有多种生长因子，包括多种淋巴因子。
白介素-1蛋白家族包括IL-1α、IL-1β、IL-1RA和最近发现的IL-1γ(也被命名为干扰素γ诱导因子，IGIF)。研究显示，相关的该基因家族可能具有广泛的生物学功能。参阅Dinarello(1994)FASEBJ.81314-1325；Dinarello(1991)Blood771627-1652；和Okamura，et al.(1995)Nature37888-91。
此外还有多种生长因子和调节因子可以调节形态发生的发展过程。包括，例如，通过与受体结合来产生信号的Toll配体，其结合的受体具有与IL-1受体相同的结构特性和作用机理。可参阅，例如，Lemaitre，et al.(1996)Cell86973-983；和Anderson(1996)Ann.Rev.Cell & Devel.Biol.12393-416。
由此可知，发现和开发新的可溶性蛋白及其受体，包括与淋巴因子类似的可溶性蛋白及其受体，将有助于开发新的疗法，以治疗那些直接或间接涉及诸如免疫系统和/或造血细胞发育、分化或功能的广泛的变性疾病或异常病症。特别是有些淋巴因子样分子可提高或加强其他淋巴因子的有利活性，发现并了解这些分子的新受体将会带来巨大利益。本发明将提供类似于白介素-1样成分的配体的一些新受体，以及相关的化合物及其用途。
附图简述

图1显示果蝇、新小杆线虫(Caenorabditis)和人DTLRs的蛋白结构比较及其与脊椎动物IL-1受体和植物抗病蛋白的关系示意图。图中将3种果蝇(Dm)DTLRs(Toll、18w和Mst ORF片段)(Morisatoand Anderson(1995)Ann.Rev.Genet.29371-399；Chiang andBeachy(1994)Mech.Develop.47225-239；Mitcham，et al.(1996)J.Biol.Chem.2715777-5783；和Eldon，et al.(1994)Develop.120885-899)与4种完整人(Hu)受体(DTLRs 1-4)和一种部分人(Hu)受体(DTLR5)进行排列比较。受体胞外域中被PRINTS标记(Attwood，et al.，(1997)Nucleic Acids Res.25212-217)的各LRRs均用方框标明；位于LRR阵列C末端或N末端侧翼的“顶部”及“底部”的Cys富集簇分别描绘成对立的半圆。与Toll和18w的784和977个氨基酸残基的延伸部分相比，DTLRs 1-5的胞外域较小(分别为558、570、690和652个氨基酸残基)，这主要是因为其内部Cys富集区域缺失。DmMst和HuDTLRs的不完全链(胞外域分别约为519和153个氨基酸残基)用虚线表示。在膜下标明的是DTLRs、IL-1型受体(IL-1Rs)、细胞内蛋白Myd88和烟草抗病基因N产物(DRgN)所共有的胞内信号组件。可参阅，例如，Hardiman，et al.(1996)Oncogene132467-2475和Rock.et al.(1998)Proc.Nat’l Acad.Sci.USA95588-。其他结构域还包括IL-1Rs中的Ig样组件三聚体(二硫键连接的环)；DRgN蛋白的特征是含有NTPase结构域(方框)，而Myd88具有一种死亡结构域(黑色椭圆)。
图2A-2C显示Toll样和IL-1样细胞因子受体以及两种趋异模块化蛋白的信号结构域保守结构模式。图2A-2B显示TH共有结构域的序列比对。DTLRs的标记方法与图1相同；人(Hu)或小鼠(Mo)IL-1家族受体(IL-1R 1-6)是按照前人的建议依次编号(Hardiman，et al.(1996)Oncogene132467-2475)；Myd88以及来自烟草(To)和亚麻L.usitatissimum(Lu)的序列分别代表较大的多结构域分子的C-端和N-端结构域。序列的无空位区(编号1-10)加框表示。有害的突变用三角标明，而将箭头所指部位的N-端截断会破坏人IL-1R1的生物活性(Heguy，et al.(1992)J.Biol.Chem.2672605-2609)。PHD(Rost and Sander(1994)Proteins1955-72)和DSC(Kingand Sternbery(1996)Protein Sci.52298-2310)二级结构预测结果中的α-螺旋(H)、β-链(E)或卷曲(L)均标出。氨基酸阴影图描述出化学性质类似的残基疏水性残基、酸性残基、碱性残基、Cys、芳香族残基、结构破坏性残基以及微小残基。IL-1Rs、DTLRs以及全排列(ALL)的序列分析图式均来自Consensus，严格度为75％。用于标明氨基酸亚类的符号为(详情见互联网站点)o，醇；1，脂肪族；·，任意氨基酸；a，芳香族；c，带电荷的；h，疏水性；-，负电性；p，极性；+，正电性；s，小；u，微小；t，转角样。图2C显示预测的TH β/α结构域折叠的拓扑结构图。平行β-折叠(β-链A-E用黄色三角标示)是从其C-末端观测；α-螺旋(标号1-5的圆圈)与β-链相联。链的联接处可位于前部(可见)或后部(隐藏)。位于β-折叠C-末端的保守带电残基用灰色标注(Asp)，或标成单独的黑色残基(Arg)(见正文)。
图3显示信号结构域超家族的进化。利用Neighbor-Joining方法(Thompson.et al.(1994)Nucleic Acids Res.224673-4680)可由图2A-2B的多重TH组件比对结果产生系统树。比对中标记了蛋白；提供的系统树是由TreeView产生。
图4A-4D描述人DTLR基因的FISH染色体作图。将用于定位的生物素标记DTLR cDNA探针与来自人淋巴细胞同步培养物的变性染色体杂交。FISH作图结果(左侧，图4A，DTLR2；4B，DTLR3；4C，DTLR4；4D，DTLR5)与染色体带的比对是将FISH信号与DAPI显带的染色体相叠加而完成的(中间图)。Heng and Tsui(1994)Meth.Molec.Biol.33109-122。分析结果被总结成染色体模式图的形式(右侧图)。
图5A-5F显示人DTLRs的mRNA印迹分析结果。用每道约含有2μgpoly(A)+RNA的多种人类组织印迹(He，心脏；Br，脑；P1，胎盘；Lu，肺；Li，肝脏；Mu，肌肉；Ki，肾；Pn，胰腺；Sp，脾；Th，胸腺；Pr，前列腺；Te，睾丸；Ov，卵巢；SI，小肠；Co，结肠；PBL，外周血淋巴细胞)和癌细胞系印迹(早幼粒细胞白血病，HL60；子宫颈癌，HELAS3；慢性髓细胞性白血病，K562；淋巴母细胞白血病，Molt4；结肠直肠腺癌，SW480；黑素瘤，G361；伯基特淋巴瘤；结肠直肠腺癌，SW480；肺癌，A549)与编码上述DTLR1(图5A-5C)、DTLR2(图5D)，DTLR3(图5E)和DTLR4(图5F)的放射性标记cDNAs杂交。利用增感屏使印迹于-70℃暴露于X射线胶片2天(图5A-5C)或1周(图5D-5F)。某些道中出现了一种0.3kB的反常核素；杂交实验排除了DTLR胞质片段的编码信息。
发明概述本发明涉及被命名为DTLR2、DTLR3、DTLR4、DTLR5、DTLR7、DTLR8、DTLR9和DTLR10的9种相关的哺乳动物新受体，如灵长类动物或人的DNAX Toll受体样分子结构，以及这些受体的生物活性。本发明包括这些多肽自身的编码核酸及其产生方法和用途。本发明所述核酸的部分特征是与文中附带的克隆化互补DNA(cDNA)序列具有同源性。在一些实施方案中，本发明提供一种物质组合物，该物质选自一种基本纯的或重组的DTLR2蛋白或肽，在其至少约12个氨基酸的长度上表现出与SEQ ID NO4的同一性；一种SEQ ID NO4的天然序列DTLR2；一种含有DTLR2序列的融合蛋白；一种基本纯的或重组的DTLR3蛋白或肽，在其至少约12个氨基酸的长度上表现出与SEQ IDNO6的同一性；一种SEQ ID NO6的天然序列DTLR3；一种含有DTLR3序列的融合蛋白；一种基本纯的或重组的DTLR4蛋白或肽，在其至少约12个氨基酸的长度上表现出与SEQ ID NO8的同一性；一种SEQ ID NO8的天然序列DTLR4；一种含有DTLR4序列的融合蛋白；一种基本纯的或重组的DTLR5蛋白或肽，在其至少约12个氨基酸的长度上表现出与SEQ ID NO10的同一性；一种SEQ ID NO10的天然序列DTLR5；一种含有DTLR5序列的融合蛋白；一种基本纯的或重组的DTLR6蛋白或肽，在其至少约12个氨基酸的长度上表现出与SEQ ID NO12、28或30的同一性；一种SEQ ID NO12、28或30的天然序列DTLR6；一种含有DTLR6序列的融合蛋白；一种基本纯的或重组的DTLR7蛋白或肽，在其至少约12个氨基酸的长度上表现出与SEQ ID NO16、18或37的同一性；一种SEQ ID NO16、18或37的天然序列DTLR7；一种含有DTLR7序列的融合蛋白；一种基本纯的或重组的DTLR8蛋白或肽，在其至少约12个氨基酸的长度上表现出与SEQ ID NO32或39的同一性；一种SEQ ID NO32或39的天然序列DTLR8；一种含有DTLR8序列的融合蛋白；一种基本纯的或重组的DTLR9蛋白或肽，在其至少约12个氨基酸的长度上表现出与SEQ ID NO22或41的同一性；一种SEQ ID NO22或41的天然序列DTLR9；一种含有DTLR9序列的融合蛋白；一种基本纯的或重组的DTLR10蛋白或肽，在其至少约12个氨基酸的长度上表现出与SEQID NO34、43或45的同一性；一种SEQ ID NO34、43或45的天然序列DTLR10；一种含有DTLR10序列的融合蛋白。优选的是这种基本纯的或分离的蛋白含有一段与DTLR2、DTLR3、DTLR4、DTLR5、DTLR6、DTLR7、DTLR8、DTLR9和DTLR10的相应部分表现出同一性的序列段，其中，所述同一性至少表现于约15个氨基酸；优选约19个氨基酸；更优选约25个氨基酸。在特别实施方案中，该物质组合物是DTLR2，它含有表2所示成熟序列；或缺乏翻译后修饰；是DTLR3，它含有表3所示成熟序列；或缺乏翻译后修饰；是DTLR4，它含有表4所示成熟序列；或缺乏翻译后修饰；是DTLR5，它含有表5所示成熟序列；或缺乏翻译后修饰；是DTLR6，它含有表6所示成熟序列；或缺乏翻译后修饰；是DTLR7，它含有表7所示成熟序列；或缺乏翻译后修饰；是DTLR8，它含有表8所示成熟序列；或缺乏翻译后修饰；是DTLR9，它含有表9所示成熟序列；或缺乏翻译后修饰；是DTLR10，它含有表10所示成熟序列；或缺乏翻译后修饰；该组合物还可以是一种蛋白或肽，这种蛋白或肽来源于一种选自哺乳动物的温血动物，包括灵长类动物，如人；至少含有SEQ ID NO4、6、26、10、12、28、30、16、18、32、22或34的一种多肽片段；带有多个具有所述同一性的片段；是DTLR2、DTLR3、DTLR4、DTLR5、DTLR6、DTLR7、DTLR8、DTLR9或DTLR10的一种天然等位变体；至少长约30个氨基酸；至少有两种对灵长类动物的DTLR2、DTLR3、DTLR4、DTLR5、DTLR6、DTLR7、DTLR8、DTLR9或DTLR10具有特异性的非重叠表位；在至少约35个氨基酸的长度上与灵长类动物的DTLR2、DTLR3、DTLR4、DTLR5、DTLR6、DTLR7、DTLR8、DTLR9或DTLR10表现出序列同一性；另外具有至少两种对灵长类动物的DTLR2、DTLR3、DTLR4、DTLR5、DTLR6、DTLR7、DTLR8、DTLR9或DTLR10具有特异性的非重叠表位；在至少约20个氨基酸的长度上与啮齿类动物的DTLR6表现出同一性；被糖基化；经天然糖基化作用后的分子量至少为100kD是一种合成多肽；附着于一种固体基质；与另一种化学部分偶联；是天然序列的一种5倍或5倍以下的取代物；或是天然序列的一种缺失变体或插入变体。
其他实施方案还包括一种组合物，该组合物含有一种无菌的DTLR2蛋白或肽；或DTLR2蛋白或肽以及一种载体，其中该载体是一种水性化合物，包括水、盐水和/或缓冲液；并且/或被配制用于口服给药、直肠给药、鼻部给药、局部给药或胃肠外给药；一种无菌的DTLR3蛋白或肽；或DTLR3蛋白或肽以及一种载体，其中该载体是一种水性化合物，包括水、盐水和/或缓冲液；并且/或被配制用于口服给药、直肠给药、鼻部给药、局部给药或胃肠外给药；一种无菌的DTLR4蛋白或肽；或DTLR4蛋白或肽以及一种载体，其中该载体是一种水性化合物，包括水、盐水和/或缓冲液；并且/或被配制用于口服给药、直肠给药、鼻部给药、局部给药或胃肠外给药；一种无菌的DTLR5蛋白或肽；或DTLR5蛋白或肽以及一种载体，其中该载体是一种水性化合物，包括水、盐水和/或缓冲液；并且/或被配制用于口服给药、直肠给药、鼻部给药、局部给药或胃肠外给药；一种无菌的DTLR6蛋白或肽；或DTLR6蛋白或肽以及一种载体，其中该载体是一种水性化合物，包括水、盐水和/或缓冲液；并且/或被配制用于口服给药、直肠给药、鼻部给药、局部给药或胃肠外给药；一种无菌的DTLR7蛋白或肽；或DTLR7蛋白或肽以及一种载体，其中该载体是一种水性化合物，包括水、盐水和/或缓冲液；并且/或被配制用于口服给药、直肠给药、鼻部给药、局部给药或胃肠外给药；一种无菌的DTLR8蛋白或肽；或DTLR8蛋白或肽以及一种载体，其中该载体是一种水性化合物，包括水、盐水和/或缓冲液；并且/或被配制用于口服给药、直肠给药、鼻部给药、局部给药或胃肠外给药；一种无菌的DTLR9蛋白或肽；或DTLR9蛋白或肽以及一种载体，其中该载体是一种水性化合物，包括水、盐水和/或缓冲液；并且/或被配制用于口服给药、直肠给药、鼻部给药、局部给药或胃肠外给药；一种无菌的DTLR10蛋白或肽；或DTLR10蛋白或肽以及一种载体，其中该载体是一种水性化合物，包括水、盐水和/或缓冲液；并且/或被配制用于口服给药、直肠给药、鼻部给药、局部给药或胃肠外给药。
在一些融合蛋白实施方案中，本发明提供一种融合蛋白，该融合蛋白含有包含表2、3、4、5、6、7、8、9或10的序列的成熟蛋白；一种检测标记或纯化标记，包括FLAG、His6或Ig序列；或另一种受体蛋白的序列。
在多种试剂盒实施方案中包括一种试剂盒，该试剂盒含有一种DTLR蛋白或多肽，以及装有该蛋白或多肽的一种隔室；和/或所述试剂盒中所含试剂的使用或处理说明书。结合化合物的实施方案包括那些含有一种抗体的抗原结合位点的化合物，这种抗体可特异性结合权利要求1的DTLR2、DTLR3、DTLR4、DTLR5、DTLR6、DTLR7、DTLR8、DTLR9或DTLR10蛋白，其中所述蛋白是一种灵长类动物蛋白；该结合化合物是一种Fv、Fab或Fab2片段；该结合化合物与另一种化学部分偶联；或所述抗体针对一种具有表2、3、4、5、6、7、8、9或10所示成熟多肽的肽序列；针对成熟的DTLR2、DTLR3、DTLR4、DTLR5、DTLR6、DTLR7、DTLR8、DTLR9或DTLR10；针对纯化的人DTLR2、DTLR3、DTLR4、DTLR5、DTLR6、DTLR7、DTLR8、DTLR9或DTLR10；经过免疫选择；是一种多克隆抗体；与变性的DTLR2、DTLR3、DTLR4、DTLR5、DTLR6、DTLR7、DTLR8、DTLR9或DTLR10结合；与抗原结合的Kd至少为30μM；附着于一种固体基质、包括珠或塑料膜；包含在一种无菌组合物中；或带有可检测标记，包括放射性标记或荧光标记。结合组合物试剂盒通常含有所述结合化合物，以及装有所述结合化合物的一种隔室；和/或所述试剂盒中所含试剂的使用或处理说明书。该试剂盒通常可以进行定量或定性分析。
本发明提供一些方法，如制备抗体的方法，该方法包括，用免疫原性剂量的一种灵长类动物DTLR2、DTLR 3、DTLR4、DTLR5、DTLR6、DTLR7、DTLR8、DTLR9或DTLR10对一种免疫系统进行免疫，从而使该抗体能够产生；或产生抗原抗体复合物的方法，该方法包括，使上述抗体与哺乳动物DTLR2、DTLR3、DTLR4、DTLR5、DTLR6、DTLR7、DTLR8、DTLR9或DTLR10蛋白相接触，从而使该复合物能够形成。
其他组合物还包括一种组合物，该组合物含有一种无菌的结合化合物，或这种结合化合物与一种载体，其中该载体是一种水性化合物，包括水、盐水和/或缓冲液；并且/或被配制用于口服给药、直肠给药、鼻部给药、局部给药或胃肠外给药。
核酸的实施方案包括编码DTLR 2-10蛋白或肽或融合蛋白的一种分离的或重组的核酸，其中，所述DTLR来源于一种哺乳动物；或所述核酸编码表2、3、4、5、6、7、8、9或10的一种抗原性肽序列；编码表2、3、4、5、6、7、8、9或10的多种抗原性肽序列；含有表2、3、4、5、6、7、8、9或10的至少17个连续核苷酸；与编码所述片段的天然cDNA至少约有80％的同一性；是一种表达载体；另含有一种复制起始点；来自一种天然来源；含有一种可检测标记；含有合成的核苷酸序列；小于6kb，优选小于3kb；来自一种哺乳动物，包括灵长类动物；含有一种天然的全长编码序列；是所述DTLR的编码基因的一种杂交探针；或是一种PCR引物、PCR产物或诱变引物。此外还提供含有这种重组核酸的细胞、组织或器官。该细胞优选为一种原核细胞；一种真核细胞；一种细菌细胞；一种酵母细胞；一种昆虫细胞；一种哺乳动物细胞；一种小鼠细胞；一种灵长类动物细胞；或一种人类细胞。提供的试剂盒含有这些核酸，以及装有该核酸的一种隔室；另装有灵长类动物DTLR2、DTLR3、DTLR4或DTLR5蛋白或多肽的一种隔室；和/或所述试剂盒中所含试剂的使用或处理说明书。该试剂盒通常可用于进行定性或定量分析。
其他实施方案还包括一种核酸，该核酸能够在30℃和盐浓度小于2M的洗涤条件下与SEQ ID NO3杂交；能够在30℃和盐浓度小于2M的洗涤条件下与SEQ ID NO5杂交；能够在30℃和盐浓度小于2M的洗涤条件下与SEQ ID NO7杂交；能够在30℃和盐浓度小于2M的洗涤条件下与SEQ ID NO9杂交；能够在30℃和盐浓度小于2M的洗涤条件下与SEQ ID NO11、13、27或29杂交；能够在30C和盐浓度小于2M的洗涤条件下与SEQ ID NO15、17或36杂交；能够在30℃和盐浓度小于2M的洗涤条件下与SEQ ID NO19、31或38杂交；能够在30℃和盐浓度小于2M的洗涤条件下与SEQ IDNO21或40杂交；能够在30℃和盐浓度小于2M的洗涤条件下与SEQ ID NO23、33、42或44杂交；在至少约30个核苷酸的片段上表现出与灵长类动物DTLR2的至少约85％的同一性；在至少约30个核苷酸的片段上表现出与灵长类动物DTLR3的至少约85％的同一性；在至少约30个核苷酸的片段上表现出与灵长类动物DTLR4的至少约85％的同一性；在至少约30个核苷酸的片段上表现出与灵长类动物DTLR5的至少约85％的同一性；该核酸优选具有这些性质，其中，洗涤条件为45℃和/或500mM的盐浓度；或所述同一性至少为90％，并且/或所述片段至少为55个核苷酸。
更优选的是洗涤条件为55℃和/或150mM的盐浓度；或所述同一性至少为95％，并且/或所述片段至少为75个核苷酸。
此外还提供一些产生配体受体复合物的方法，这些方法包括将基本纯的灵长类动物DTLR2、DTLR3、DTLR4、DTLR5、DTLR6、DTLR7、DTLR8、DTLR9或DTLR10，包括重组或合成产生的蛋白，与候选的Toll配体相接触；从而使所述复合物能够形成。
本发明还提供一种用于调节细胞或组织培养细胞的生理机能或发育的方法，该方法包括将所述细胞与哺乳动物DTLR2、DTLR3、DTLR4、DTLR5、DTLR6、DTLR7、DTLR8、DTLR9或DTLR10的一种激动剂或拮抗剂相接触。优选的是将pDC 2细胞与DTLR10的激动剂或拮抗剂相接触。
发明详述提纲I.概要II.活性III.核酸A.编码片段、序列、探针B.突变、嵌合体、融合体C.制备核酸D.含有核酸的载体、细胞IV.蛋白、肽A.片段、序列、免疫原、抗原B.突变蛋白C.激动剂/拮抗剂、功能等价物D.制备蛋白V.核酸、蛋白的制备A.合成B.重组
C.天然表源VI.抗体A.多克隆抗体B.单克隆抗体C.片段；KdD.抗独特型抗体E.杂交瘤细胞系VII.用于DTLRs 1-10定量的试剂盒及方法A.ELISAB.编码mRNA的测定C.定性/定量D.试剂盒VIII.治疗性组合物、方法A.联合组合物B.单位剂量C.给药方法IX.配体I.概要本发明提供具有特定结构和生物学性质的哺乳动物DNAX Toll样受体分子(DTLR)的氨基酸序列及DNA序列，本文的DTLR来源于灵长类动物。这些分子在文中分别被命名为DTLR2、DTLR3、DTLR4、DTLR5、DTLR6、DTLR7、DTLR8、DTLR9和DTLR10，从而使人Toll样受体家族成员的数量从1增加到10。编码这些分子的不同cDNAs均来自灵长类动物的cDNA序列库，例如人的cDNA序列库。其他灵长类动物或哺乳类动物的对应物也应考虑在内。
一些可使用的标准方法是来自，例如，Maniatis，et al.(1982)《分子克隆实验手册》，Cold Spring Harbor Laboratory，ColdSpring Harbor Press；Sambrook，et al.(1989)《分子克隆实验手册》，(第二版)vols.1-3，CSH Press，NY；Ausubel，et al.，《生物学》，Greene Publishing Associates，Brooklyn，NY；或Ausubel，et al.(1987及定期增刊)《最新分子生物学实验方法》，Greene/Wiley，New York的描述或其参考文献；这些内容均在此引入作为参考。
表1显示人DTLR1编码区的完整核苷酸序列(SEQ ID NO1)和相应的氨基酸序列(SEQ ID NO2)。还可参考Nomura，et al.(1994)DNA Res.127-35。表2显示人DTLR2编码区的完整核苷酸序列(SEQID NO3)和相应的氨基酸序列(SEQ ID NO4)。表3显示人DTLR3编码区的完整核苷酸序列(SEQ ID NO5)和相应的氨基酸序列(SEQID NO6)。表4显示人DTLR4编码区的完整核苷酸序列(SEQ ID NO7)和相应的氨基酸序列(SEQ ID NO8)；还可参考SEQ ID NO25和SEQ ID NO26。表5显示人DTLR5编码区的部分核苷酸序列(SEQID NO9)和相应的氨基酸序列(SEQ ID NO10)。表6显示人DTLR6编码区的完整核苷酸序列(SEQ ID NO11)和相应的氨基酸序列(SEQID NO12)，以及鼠DTLR6的部分序列(SEQ ID NO13、14、27、28、29和30)。表7显示人DTLR7编码区的部分核苷酸序列(SEQ IDNO15和17)和相应的氨基酸序列(SEQ ID NO16和18)；SEQ IDNO36和37则提供全长序列。表8显示人DTLR8编码区的部分核苷酸序列(SEQ ID NO19)和相应的氨基酸序列(SEQ ID NO20)，以及附加序列(SEQ ID NO31、32、38和39)。表9显示人DTLR9编码区的部分核苷酸序列(SEQ ID NO21)和相应的氨基酸序列(SEQID NO22)；还可参考SEQ ID NO40和41。表10显示人DTLR10编码区的部分核苷酸序列(SEQ ID NO23)和相应的氨基酸序列(SEQID NO24)，以及附加序列(SEQ ID NO33、34、42和43)和小鼠等啮齿动物的序列(SEQ ID NO35、44和45)。
表1诸如人等灵长类动物的DNAX Toll样受体1(DTLR1)的核苷酸序列和氨基酸序列(见SEQ ID NO1和2)。
ATG ACT AGC ATC TTC CAT TTT GCC ATT ATC TTC ATG TTA ATA CTT CAG 48Met Thr Ser Ile Phe His Phe Ala Ile Ile Phe Met Leu Ile Leu Gln-22 -20 -15 -10ATC AGA ATA CAA TTA TCT GAA GAA AGT GAA TTT TTA GTT GAT AGG TCA 96Ile Arg Ile Gln Leu Ser Glu Glu Ser Glu Phe Leu Val Asp Arg Ser-5 1 5 10AAA AAC GGT CTC ATC CAC GTT CCT AAA GAC CTA TCC CAG AAA ACA ACA144Lys Asn Gly Leu Ile His Val Pro Lys Asp Leu Ser Gln Lys Thr Thr15 20 25ATC TTA AAT ATA TCG CAA AAT TAT ATA TCT GAG CTT TGG ACT TCT GAC192Ile Leu Asn Ile Ser Gln Asn Tyr Ile Ser Glu Leu Trp Thr Ser Asp30 35 40ATC TTA TCA CTG TCA AAA CTG AGG ATT TTG ATA ATT TCT CAT AAT AGA240Ile Leu Ser Leu Ser Lys Leu Arg Ile Leu Ile Ile Ser His Asn Arg45 50 55ATC CAG TAT CTT GAT ATC AGT GTT TTC AAA TTC AAC CAG GAA TTG GAA288Ile Gln Tyr Leu Asp Ile Ser Val Phe Lys Phe Asn Gln Glu Leu Glu60 65 70TAC TTG GAT TTG TCC CAC AAC AAG TTG GTG AAG ATT TCT TGC CAC CCT336Tyr Leu Asp Leu Ser His Asn Lys Leu Val Lys Ile Ser Cys His Pro75 80 85 90ACT GTG AAC CTC AAG CAC TTG GAC CTG TCA TTT AAT GCA TTT GAT GCC384Thr Val Asn Leu Lys His Leu Asp Leu Ser Phe Asn Ala Phe Asp Ala95 100 105CTG CCT ATA TGC AAA GAG TTT GGC AAT ATG TCT CAA CTA AAA TTT CTG432Leu Pro Ile Cys Lys Glu Phe Gly Asn Met Ser Gln Leu Lys Phe Leu110 115 120GGG TTG AGC ACC ACA CAC TTA GAA AAA TCT AGT GTG CTG CCA ATT GCT480Gly Leu Ser Thr Thr His Leu Glu Lys Set Set val Leu Pro Ile Ala125 130 135CAT TTG AAT ATC AGC AAG GTC TTG CTG GTC TTA GGA GAG ACT TAT GGG528His Leu Asn Ile Set Lys Val Leu Leu Val Leu Gly Glu Thr Tyr Gly140 145 150GAA AAA GAA GAC CCT GAG GGC CTT CAA GAC TTT AAC ACT GAG AGT CTG576Glu Lys Glu Asp Pro Glu Gly Leu Gln Asp Phe Asn Thr Giu Set Leu155 160 165 170CAC ATT GTG TTC CCC ACA AAC AAA GAA TTC CAT TTT ATT TTG GAT GTG624His Ile Val Phe Pro Thr Asn Lys Glu Phe His Phe Ile Leu Asp Val175 180 185
TCA GTC AAG ACT GTA GCA AAT CTG GAA CTA TCT AAT ATC AAA TGT GTG 672Ser Val Lys Thr Val Ala Asn Leu Glu Leu Ser Asn Ile Lys Cys Val190 195 200CTA GAA GAT AAC AAA TGT TCT TAC TTC CTA AGT ATT CTG GCG AAA CTT 720Leu Glu Asp Asn Lys Cys Ser Tyr Phe Leu Ser Ile Leu Ala Lys Leu205 210 215CAA ACA AAT CCA AAG TTA TCA AGT CTT ACC TTA AAC AAC ATT GAA ACA 768Gln Thr Asn Pro Lys Leu Ser Ser Leu Thr Leu Asn Asn Ile Glu Thr220 225 230ACT TGG AAT TCT TTC ATT AGG ATC CTC CAA CTA GTT TGG CAT ACA ACT 816Thr Trp Asn Ser Phe Ile Arg Ile Leu Gln Leu Val Trp His Thr Thr235 240 245 250GTA TGG TAT TTC TCA ATT TCA AAC GTG AAG CTA CAG GGT CAG CTG GAC 864Val Trp Tyr Phe Ser Ile Ser Asn Val Lys Leu Gln Gly Gln Leu Asp255 260 265TTC AGA GAT TTT GAT TAT TCT GGC ACT TCC TTG AAG GCC TTG TCT ATA 912Phe Arg Asp Phe Asp Tyr Ser Gly Thr Ser Leu Lys Ala Leu Ser Ile270 275 280CAC CAA GTT GTC AGC GAT GTG TTC GGT TTT CCG CAA AGT TAT ATC TAT 960His Gln Val Val Ser Asp Val Phe Gly Phe Pro Gln Ser Tyr Ile Tyr285 290 295GAA ATC TTT TCG AAT ATG AAC ATC AAA AAT TTC ACA GTG TCT GGT ACA1008Glu Ile Phe Ser Asn Met Asn Ile Lys Asn Phe Thr Val Ser Gly Thr300 305 310CGC ATG GTC CAC ATG CTT TGC CCA TCC AAA ATT AGC CCG TTC CTG CAT1056Arg Met Val His Met Leu Cys Pro Ser Lys Ile Ser Pro Phe Leu His315 320 325 330TTG GAT TTT TCC AAT AAT CTC TTA ACA GAC ACG GTT TTT GAA AAT TGT1104Leu Asp Phe Ser Asn Asn Leu Leu Thr Asp Thr Val Phe Glu Asn Cys335 340 345GGG CAC CTT ACT GAG TTG GAG ACA CTT ATT TTA CAA ATG AAT CAA TTA1152Gly His Leu Thr Glu Leu Glu Thr Leu Ile Leu Gln Met Asn Gln Leu350 355 360AAA GAA CTT TCA AAA ATA GCT GAA ATG ACT ACA CAG ATG AAG TCT CTG1200Lys Glu Leu Ser Lys Ile Ala Glu Met Thr Thr Gln Met Lys Ser Leu365 370 375CAA CAA TTG GAT ATT AGC CAG AAT TCT GTA AGC TAT GAT GAA AAG AAA1248Gln Gln Leu Asp Ile Ser Gln Asn Ser Val Ser Tyr Asp Glu Lys Lys380 385 390GGA GAC TGT TCT TGG ACT AAA AGT TTA TTA AGT TTA AAT ATG TCT TCA1296Gly Asp Cys Ser Trp Thr Lys Ser Leu Leu Ser Leu Asn Met Ser Ser395 400 405 410
AAT ATA CTT ACT GAC ACT ATT TTC AGA TGT TTA CCT CCC AGG ATC AAG 1344Asn Ile Leu Thr Asp Thr Ile Phe Arg Cys Leu Pro Pro Arg Ile Lys415 420 425GTA CTT GAT CTT CAC AGC AAT AAA ATA AAG AGC ATT CCT AAA CAA GTC 1392Val Leu Asp Leu His Ser Asn Lys Ile Lys Ser Ile Pro Lys Gln Val430 435 440GTA AAA CTG GAA GCT TTG CAA GAA CTC AAT GTT GCT TTC AAT TCT TTA 1440Val Lys Leu Glu Ala Leu Gln Glu Leu Asn Val Ala Phe Asn Ser Leu445 450 455ACT GAC CTT CCT GGA TGT GGC AGC TTT AGC AGC CTT TCT GTA TTG ATC 1488Thr Asp Leu Pro Gly Cys Gly Ser Phe Ser Ser Leu Ser Val Leu Ile460 465 470ATT GAT CAC AAT TCA GTT TCC CAC CCA TCA GCT GAT TTC TTC CAG AGC 1536Ile Asp His Asn Ser Val Ser His Pro Ser Ala Asp Phe Phe Gln Ser475 480 485 490TGC CAG AAG ATG AGG TCA ATA AAA GCA GGG GAC AAT CCA TTC CAA TGT 1584Cys Gln Lys Met Arg Ser Ile Lys Ala Gly Asp Asn Pro Phe Gln Cys495 500 505ACC TGT GAG CTC GGA GAA TTT GTC AAA AAT ATA GAC CAA GTA TCA AGT 1632Thr Cys Glu Leu Gly Glu Phe Val Lys Asn Ile Asp Gln Val Ser Ser510 515 520GAA GTG TTA GAG GGC TGG CCT GAT TCT TAT AAG TGT GAC TAC CCG GAA 1680Glu Val Leu Glu Gly Trp Pro Asp Ser Tyr Lys Cys Asp Tyr Pro Glu525 530 535AGT TAT AGA GGA ACC CTA CTA AAG GAC TTT CAC ATG TCT GAA TTA TCC 1728Ser Tyr Arg Gly Thr Leu Leu Lys Asp Phe His Met Ser Glu Leu Ser540 545 550TGC AAC ATA ACT CTG CTG ATC GTC ACC ATC GTT GCC ACC ATG CTG GTG 1776Cys Asn Ile Thr Leu Leu Ile Val Thr Ile Val Ala Thr Met Leu Val555 560 565 570TTG GCT GTG ACT GTG ACC TCC CTC TGC ATC TAC TTG GAT CTG CCC TGG 1824Leu Ala Val Thr Val Thr Ser Leu Cys Ile Tyr Leu Asp Leu Pro Trp575 580 585TAT CTC AGG ATG GTG TGC CAG TGG ACC CAG ACC CGG CGC AGG GCC AGG 1872Tyr Leu Arg Met Val Cys Gln Trp Thr Gln Thr Arg Arg Arg Ala Arg590 595 600AAC ATA CCC TTA GAA GAA CTC CAA AGA AAT CTC CAG TTT CAT GCA TTT 1920Asn Ile Pro Leu Glu Glu Leu Gln Arg Asn Leu Gln Phe His Ala Phe605 610 615
ATT TCA TAT AGT GGG CAC GAT TCT TTC TGG GTG AAG AAT GAA TTA TTG 1968Ile Ser Tyr Ser Gly His Asp Ser Phe Trp Val Lys Asn Glu Leu Leu620 625 630CCA AAC CTA GAG AAA GAA GGT ATG CAG ATT TGC CTT CAT GAG AGA AAC 2016Pro Asn Leu Glu Lys Glu Gly Met Gln Ile Cys Leu His Glu Arg Asn635 640 645 650TTT GTT CCT GGC AAG AGC ATT GTG GAA AAT ATC ATC ACC TGC ATT GAG 2064Phe Val Pro Gly Lys Ser Ile Val Glu Asn Ile Ile Thr Cys Ile Glu655 660 665AAG AGT TAC AAG TCC ATC TTT GTT TTG TCT CCC AAC TTT GTC CAG AGT 2112Lys Ser Tyr Lys Ser Ile Phe Val Leu Ser Pro Asn Phe Val Gln Ser670 675 680GAA TGG TGC CAT TAT GAA CTC TAC TTT GCC CAT CAC AAT CTC TTT CAT 2160Glu Trp Cys His Tyr Glu Leu Tyr Phe Ala His His Asn Leu Phe His685 690 695GAA GGA TCT AAT AGC TTA ATC CTG ATC TTG CTG GAA CCC ATT CCG CAG 2208Glu Gly Ser Asn Ser Leu Ile Leu Ile Leu Leu Glu Pro Ile Pro Gln700 705 710TAC TCC ATT CCT AGC AGT TAT CAC AAG CTC AAA AGT CTC ATG GCC AGG 2256Tyr Ser Ile Pro Ser Ser Tyr His Lys Leu Lys Ser Leu Met Ala Arg715 720 725 730AGG ACT TAT TTG GAA TGG CCC AAG GAA AAG AGC AAA CGT GGC CTT TTT 2304Arg Thr Tyr Leu Glu Trp Pro Lys Glu Lys Ser Lys Arg Gly Leu Phe735 740 745TGG GCT AAC TTA AGG GCA GCC ATT AAT ATT AAG CTG ACA GAG CAA GCA 2352Trp Ala Asn Leu Arg Ala Ala Ile Asn Ile Lys Leu Thr Glu Gln Ala750 755 760AAG AAA TAGTCTAGA 2367Lys LysMTSIFHFAIIFMLILQIRIQLSEESEFLVDRSKNGLIHVPKDLSQKTTILNISQNYISELWTSDILSLSKLRILIISHNRIQYLDISVFKFNQELEYLDLSHNKLVKISCHPTVNLKHLDLSFNAFDALPICKEFGNMSQLKFLGLSTTHLEKSSVLPIAHLNISKVLLVLGETYGEKEDPEGLQDFNTESLHIVFPTNKEFHFILDVSVKTVANLELSNIKCVLEDNKCSYFLSILAKLQTNPKLSSLTLNNIETTWNSFIRILQLVWHTTVWYFSISNVKLQGQLDFRDFDYSGTSLKALSIHQVVSDVFGFPQSYIYEIFSNMNIKNFTVSGTRMVHMLCPSKISPFLHLDFSNNLLTDTVFENCGHLTELETLILQMNQLKELSKIAEMTTQMKSLQQLDISQNSVSYDEKKGDCSWTKSLLSLNMSSNILTDTIFRCLPPRIKVLDLHSNKIKSIPKQVVKLEALQELNVAFNSLTDLPGCGSFSSLSVLIIDHNSVSHPSADFFQSCQKMRSIKAGDNPFQCTCELGEFVKNIDQVSSEVLEGWPDSYKCDYPESYRGTLLKIFHMSELSCNITLLIVTIVATMLVLAVTVTSLCIYLDLPWYLRMVCQWTQTRRRARNIPLEELQRNLQFHAFISYSGHDSFWVKNELLPNLEKEGMQICLHERNFVPGKSIVENIITCIEKSYKSIFVLSPNFVQSEWCHYELYFAHHNLFHEGSNSLILILLEPIPQYSIPSSYHKLKSLMARRTYLEWPKEKSKRGLFWANLRAAINIKLTEQAKK
表2诸如人等灵长类动物的DNAX Toll样受体2(DTLR2)的核苷酸序列和氨基酸序列(见SEQ ID NO3和4)。
ATG CCA CAT ACT TTG TGG ATG GTG TGG GTC TTG GGG GTC ATC ATC AGC 48Met Pro His Thr Leu Trp Met Val Trp Val Leu Gly Val Ile Ile Ser-22 -20 -15 -10CTC TCC AAG GAA GAA TCC TCC AAT CAG GCT TCT CTG TCT TGT GAC CGC 96Leu Ser Lys Glu Glu Ser Ser Asn Gln Ala Ser Leu Ser Cys Asp Arg-5 1 5 10AAT GGT ATC TGC AAG GGC AGC TCA GGA TCT TTA AAC TCC ATT CCC TCA 144Asn Gly Ile Cys Lys Gly Ser Ser Gly Ser Leu Asn Ser Ile Pro Ser15 20 25GGG CTC ACA GAA GCT GTA AAA AGC CTT GAC CTG TCC AAC AAC AGG ATC 192Gly Leu Thr Glu Ala Val Lys Ser Leu Asp Leu Ser Asn Asn Arg Ile30 35 40ACC TAC ATT AGC AAC AGT GAC CTA CAG AGG TGT GTG AAC CTC CAG GCT 240Thr Tyr Ile Ser Asn Ser Asp Leu Gln Arg Cys Val Asn Leu Gln Ala45 50 55CTG GTG CTG ACA TCC AAT GGA ATT AAC ACA ATA GAG GAA GAT TCT TTT 288Leu Val Leu Thr Ser Asn Gly Ile Asn Thr Ile Glu Glu Asp Ser Phe60 65 70TCT TCC CTG GGC AGT CTT GAA CAT TTA GAC TTA TCC TAT AAT TAC TTA 336Ser Ser Leu Gly Ser Leu Glu His Leu Asp Leu Ser Tyr Asn Tyr Leu75 80 85 90TCT AAT TTA TCG TCT TCC TGG TTC AAG CCC CTT TCT TCT TTA ACA TTC 384Ser Asn Leu Ser Ser Ser Trp Phe Lys Pro Leu Ser Ser Leu Thr Phe95 100 105TTA AAC TTA CTG GGA AAT CCT TAC AAA ACC CTA GGG GAA ACA TCT CTT 432Leu Asn Leu Leu Gly Asn Pro Tyr Lys Thr Leu Gly Glu Thr Ser Leu110 115 120TTT TCT CAT CTC ACA AAA TTG CAA ATC CTG AGA GTG GGA AAT ATG GAC 480Phe Ser His Leu Thr Lys Leu Gln Ile Leu Arg Val Gly Asn Met Asp125 130 135ACC TTC ACT AAG ATT CAA AGA AAA GAT TTT GCT GGA CTT ACC TTC CTT 528Thr Phe Thr Lys Ile Gln Arg Lys Asp Phe Ala Gly Leu Thr Phe Leu140 145 150GAG GAA CTT GAG ATT GAT GCT TCA GAT CTA CAG AGC TAT GAG CCA AAA 576Glu Glu Leu Glu Ile Asp Ala Ser Asp Leu Gln Ser Tyr Glu Pro Lys155 160 165 170AGT TTG AAG TCA ATT CAG AAC GTA AGT CAT CTG ATC CTT CAT ATG AAG 624Ser Leu Lys Ser Ile Gln Asn Val Ser His Leu Ile Leu His Met Lys175 180 185
CAG CAT ATT TTA CTG CTG GAG ATT TTT GTA GAT GTT ACA AGT TCC GTG672Gln His Ile Leu Leu Leu Glu Ile Phe Val Asp Val Thr Ser Ser Val190 195 200GAA TGT TTG GAA CTG CGA GAT ACT GAT TTG GAC ACT TTC CAT TTT TCA720Glu Cys Leu Glu Leu Arg Asp Thr Asp Leu Asp Thr Phe His Phe Ser205 210 215GAA CTA TCC ACT GGT GAA ACA AAT TCA TTG ATT AAA AAG TTT ACA TTT768Glu Leu Ser Thr Gly Glu Thr Asn Ser Leu Ile Lys Lys Phe Thr Phe220 225 230AGA AAT GTG AAA ATC ACC GAT GAA AGT TTG TTT CAG GTT ATG AAA CTT816Arg Asn Val Lys Ile Thr Asp Glu Ser Leu Phe Gln Val Met Lys Leu235 240 245 250TTG AAT CAG ATT TCT GGA TTG TTA GAA TTA GAG TTT GAT GAC TGT ACC864Leu Asn Gln Ile Ser Gly Leu Leu Glu Leu Glu Phe Asp Asp Cys Thr255 260 265CTT AAT GGA GTT GGT AAT TTT AGA GCA TCT GAT AAT GAC AGA GTT ATA912Leu Asn Gly Val Gly Asn Phe Arg Ala Ser Asp Asn Asp Arg Val Ile270 275 280GAT CCA GGT AAA GTG GAA ACG TTA ACA ATC CGG AGG CTG CAT ATT CCA960Asp Pro Gly Lys Val Glu Thr Leu Thr Ile Arg Arg Leu His Ile Pro285 290 295AGG TTT TAC TTA TTT TAT GAT CTG AGC ACT TTA TAT TCA CTT ACA GAA 1008Arg Phe Tyr Leu Phe Tyr Asp Leu Ser Thr Leu Tyr Ser Leu Thr Glu300 305 310AGA GTT AAA AGA ATC ACA GTA GAA AAC AGT AAA GTT TTT CTG GTT CCT 1056Arg Val Lys Arg Ile Thr Val Glu Asn Ser Lys Val Phe Leu Val Pro315 320 325 330TGT TTA CTT TCA CAA CAT TTA AAA TCA TTA GAA TAC TTG GAT CTC AGT 1104Cys Leu Leu Ser Gln His Leu Lys Ser Leu Glu Tyr Leu Asp Leu Ser335 340 345GAA AAT TTG ATG GTT GAA GAA TAC TTG AAA AAT TCA GCC TGT GAG GAT 1152Glu Asn Leu Met Val Glu Glu Tyr Leu Lys Asn Ser Ala Cys Glu Asp350 355 360GCC TGG CCC TCT CTA CAA ACT TTA ATT TTA AGG CAA AAT CAT TTG GCA 1200Ala Trp Pro Ser Leu Gln Thr Leu Ile Leu Arg Gln Asn His Leu Ala365 370 375TCA TTG GAA AAA ACC GGA GAG ACT TTG CTC ACT CTG AAA AAC TTG ACT 1248Ser Leu Glu Lys Thr Gly Glu Thr Leu Leu Thr Leu Lys Asn Leu Thr380 385 390AAC ATT GAT ATC AGT AAG AAT AGT TTT CAT TCT ATG CCT GAA ACT TGT 1296Asn Ile Asp Ile Ser Lys Asn Ser Phe His Ser Met Pro Glu Thr Cys395 400 405 410
CAG TGG CCA GAA AAG ATG AAA TAT TTG AAC TTA TCC AGC ACA CGA ATA 1344Gln Trp Pro Glu Lys Met Lys Tyr Leu Asn Leu Ser Ser Thr Arg Ile415 420 425CAC AGT GTA ACA GGC TGC ATT CCC AAG ACA CTG GAA ATT TTA GAT GTT 1392His Ser Val Thr Gly Cys Ile Pro Lys Thr Leu Glu Ile Leu Asp Val430 435 440AGC AAC AAC AAT CTC AAT TTA TTT TCT TTG AAT TTG CCG CAA CTC AAA 1440Ser Asn Asn Asn Leu Asn Leu Phe Ser Leu Asn Leu Pro Gln Leu Lys445 450 455GAA CTT TAT ATT TCC AGA AAT AAG TTG ATG ACT CTA CCA GAT GCC TCC 1488Glu Leu Tyr Ile Ser Arg Asn Lys Leu Met Thr Leu Pro Asp Ala Ser460 465 470CTC TTA CCC ATG TTA CTA GTA TTG AAA ATC AGT AGG AAT GCA ATA ACT 1536Leu Leu Pro Met Leu Leu Val Leu Lys Ile Ser Arg Asn Ala Ile Thr475 480 485 490ACG TTT TCT AAG GAG CAA CTT GAC TCA TTT CAC ACA CTG AAG ACT TTG 1584Thr Phe Sar Lys Glu Gln Leu Asp Ser Phe His Thr Leu Lys Thr Leu495 500 505GAA GCT GGT GGC AAT AAC TTC ATT TGC TCC TGT GAA TTC CTC TCC TTC 1632Glu Ala Gly Gly Asn Asn Phe Ile Cys Ser Cys Glu Phe Leu Ser Phe510 515 520ACT CAG GAG CAG CAA GCA CTG GCC AAA GTC TTG ATT GAT TGG CCA GCA 1680Thr Gln Glu Gln Gln Ala Leu Ala Lys Val Leu Ile Asp Trp Pro Ala525 530 535AAT TAC CTG TGT GAC TCT CCA TCC CAT GTG CGT GGC CAG CAG GTT CAG 1728Asn Tyr Leu Cys Asp Ser Pro Ser His Val Arg Gly Gln Gln Val Gln540 545 550GAT GTC CGC CTC TCG GTG TCG GAA TGT CAC AGG ACA GCA CTG GTG TCT 1776Asp Val Arg Leu Ser Val Ser Glu Cys His Arg Thr Ala Leu val Ser555 560 565 570GGC ATG TGC TGT GCT CTG TTC CTG CTG ATC CTG CTC ACG GGG GTC CTG 1824Gly Met Cys Cys Ala Leu Phe Leu Leu Ile Leu Leu Thr Gly Val Leu575 580 585TGC CAC CGT TTC CAT GGC CTG TGG TAT ATG AAA ATG ATG TGG GCC TGG 1872Cys His Arg Phe His Gly Leu Trp Tyr Met Lys Met Met Trp Ala Trp590 595 600CTC CAG GCC AAA AGG AAG CCC AGG AAA GCT CCC AGC AGG AAC ATC TGC 1920Leu Gln Ala Lys Arg Lys Pro Arg Lys Ala Pro Ser Arg Asn Ile Cys605 610 615
TAT GAT GCA TTT GTT TCT TAC AGT GAG CGG GAT GCC TAC TGG GTG GAG 1968Tyr Asp Ala Phe Val Ser Tyr Ser Glu Arg Asp Ala Tyr Trp Val Glu620 625 630AAC CTT ATG GTC CAG GAG CTG GAG AAC TTC AAT CCC CCC TTC AAG TTG 2016Asn Leu Met Val Gln Glu Leu Glu Asn Phe Asn Pro Pro Phe Lys Leu635 640 645 650TGT CTT CAT AAG CGG GAC TTC ATT CCT GGC AAG TGG ATC ATT GAC AAT 2064Cys Leu His Lys Arg Asp Phe Ile Pro Gly Lys Trp Ile Ile Asp Asn655 660 665ATC ATT GAC TCC ATT GAA AAG AGC CAC AAA ACT GTC TTT GTG CTT TCT 2112Ile Ile Asp Ser Ile Glu Lys Ser His Lys Thr Val Phe Val Leu Ser670 675 680GAA AAC TTT GTG AAG AGT GAG TGG TGC AAG TAT GAA CTG GAC TTC TCC 2160Glu Asn Phe Val Lys Ser Glu Trp Cys Lys Tyr Glu Leu Asp Phe Ser685 690 695CAT TTC CGT CTT TTT GAA GAG AAC AAT GAT GCT GCC ATT CTC ATT CTT 2208His Phe Arg Leu Phe Glu Glu Asn Asn Asp Ala Ala Ile Leu Ile Leu700 705 710CTG GAG CCC ATT GAG AAA AAA GCC ATT CCC CAG CGC TTC TGC AAG CTG 2256Leu Glu Pro Ile Glu Lys Lys Ala Ile Pro Gln Arg Phe Cys Lys Leu715 720 725 730CGG AAG ATA ATG AAC ACC AAG ACC TAC CTG GAG TGG CCC ATG GAC GAG 2304Arg Lys Ile Met Asn Thr Lys Thr Tyr Leu Glu Trp Pro Met Asp Glu735 740 745GCT CAG CGG GAA GGA TTT TGG GTA AAT CTG AGA GCT GCG ATA AAG TCC 2352Ala Gln Arg Glu Gly Phe Trp Val Asn Leu Arg Ala Ala Ile Lys Ser750 755 760TAG 2355MPHTLWMVWVLGVIISLSKEESSNQASLSCDRNGICKGSSGSLNSIPSGLTEAVKSLDLSNNRITYISNSDLQRCVNLQALVLTSNGINTIEEDSFSSLGSLEHLDLSYNYLSNLSSSWFKPLSSLTFLNLLGNPYKTLGETSLFSHLTKLQILRVGNMDTFTKIQRKDFAGLTFLEELEIDASDLQSYEPKSLKSIQNVSHLILHMKQHILLLEIFVDVTSSVECLELRDTDLDTFHFSELSTGETNSLIKKFTFRNVKITDESLFQVMKLLNQISGLLELEFDDCTLNGVGNFRASDNDRVIDPGKVETLTIRRLHIPRFYLFYDLSTLYSLTEEVKRITVENSKVFLVPCLLSQHLKSLEYLDLSENLMVEEYLKNSACEDAWPSLQTLILRQNHLASLEKTGETLLTLKNLTNIDISKNSFHSMPETCQWPEKMKYLNLSSIRIHSVTGCIPKTLEILDVSNNNLNLFSLNLPQLKELYISRNKLMTLPDASLLPMLLVLKISRNAITTFSKEQLDSFHTLKTLEAGGNNFICSCEFLSFTQEQQALAKVLIDWPANYLCDSPSHVRGQQVQDVRLSVSECHRTALVSGMCCALFLLILLTGVLCHRFHGLWYMKMMWAWLQAKRKPRKAPSRNICYDAFVSYSERDAYWVENLMVQELENFNPPFKLCLHKRDFIPGKWIIDNIIDSIEKSHKTVFVLSENFVKSEWCKYELDFSHFRLFEENNDAAILILLEPIEKKAIPQRFCKLRKIMNTKTYLEWPMDEAQREGFWVNLRAAIKS
表3诸如人等灵长类动物的DNAX Toll样受体3(DTLR3)的核苷酸序列和氨基酸序列(见SEQ ID NO5和6)。
ATG AGA CAG ACT TTG CCT TGT ATC TAC TTT TGG GGG GGC CTT TTG CCC 48Met Arg Gln Thr Leu Pro Cys Ile Tyr Phe Trp Gly Gly Leu Leu Pro-21 -20 -15 -10TTT GGG ATG CTG TGT GCA TCC TCC ACC ACC AAG TGC ACT GTT AGC CAT 96Phe Gly Met Leu Cys Ala Ser Ser Thr Thr Lys Cys Thr Val Ser His-51 5 10GAA GTT GCT GAC TGC AGC CAC CTG AAG TTG ACT CAG GTA CCC GAT GAT 144Glu Val Ala Asp Cys Ser His Leu Lys Leu Thr Gln Val Pro Asp Asp15 20 25CTA CCC ACA AAC ATA ACA GTG TTG AAC CTT ACC CAT AAT CAA CTC AGA 192Leu Pro Thr Asn Ile Thr Val Leu Asn Leu Thr His Asn Gln Leu Arg30 35 40AGA TTA CCA GCC GCC AAC TTC ACA AGG TAT AGC CAG CTA ACT AGC TTG 240Arg Leu Pro Ala Ala Asn Phe Thr Arg Tyr Ser Gln Leu Thr Ser Leu45 50 55GAT GTA GGA TTT AAC ACC ATC TCA AAA CTG GAG CCA GAA TTG TGC CAG 288Asp Val Gly Phe Asn Thr Ile Ser Lys Leu Glu Pro Glu Leu Cys Gln60 65 70 75AAA CTT CCC ATG TTA AAA GTT TTG AAC CTC CAG CAC AAT GAG CTA TCT 336Lys Leu Pro Met Leu Lys Val Leu Asn Leu Gln His Asn Glu Leu Ser80 85 90CAA CTT TCT GAT AAA ACC TTT GCC TTC TGC ACG AAT TTG ACT GAA CTC 384Gln Leu Ser Asp Lys Thr Phe Ala Phe Cys Thr Asn Leu Thr Glu Leu95 100 105CAT CTC ATG TCC AAC TCA ATC CAG AAA ATT AAA AAT AAT CCC TTT GTC 432His Leu Met Ser Asn Ser Ile Gln Lys Ile Lys Asn Asn Pro Phe Val110 115 120AAG CAG AAG AAT TTA ATC ACA TTA GAT CTG TCT CAT AAT GGC TTG TCA 480Lys Gln Lys Asn Leu Ile Thr Leu Asp Leu Ser His Asn Gly Leu Ser125 130 135TCT ACA AAA TTA GGA ACT CAG GTT CAG CTG GAA AAT CTC CAA GAG CTT 528Ser Thr Lys Leu Gly Thr Gln Val Gln Leu Glu Asn Leu Gln Glu Leu140 145 150 155CTA TTA TCA AAC AAT AAA ATT CAA GCG CTA AAA AGT GAA GAA CTG GAT 576Leu Leu Ser Asn Asn Lys Ile Gln Ala Leu Lys Ser Glu Glu Leu Asp160 165 170ATC TTT GCC AAT TCA TCT TTA AAA AAA TTA GAG TTG TCA TCG AAT CAA 624Ile Phe Ala Asn Ser Ser Leu Lys Lys Leu Glu Leu Ser Ser Asn Gln175 180 185
ATT AAA GAG TTT TCT CCA GGG TGT TTT CAC GCA ATT GGA AGA TTA TTT 672Ile Lys Glu Phe Ser Pro Gly Cys Phe His Ala Ile Gly Arg Leu Phe190 195 200GGC CTC TTT CTG AAC AAT GTC CAG CTG GGT CCC AGC CTT ACA GAG AAG 720Gly Leu Phe Leu Asn Asn Val Gln Leu Gly Pro Ser Leu Thr Glu Lys205 210 215CTA TGT TTG GAA TTA GCA AAC ACA AGC ATT CGG AAT CTG TCT CTG AGT 768Leu Cys Leu Glu Leu Ala Asn Thr Ser Ile Arg Asn Leu Ser Leu Ser220 225 230 235AAC AGC CAG CTG TCC ACC ACC AGC AAT ACA ACT TTC TTG GGA CTA AAG 816Asn Ser Gln Leu Ser Thr Thr Ser Asn Thr Thr Phe Leu Gly Leu Lys240 245 250TGG ACA AAT CTC ACT ATG CTC GAT CTT TCC TAC AAC AAC TTA AAT GTG 864Trp Thr Asn Leu Thr Met Leu Asp Leu Ser Tyr Asn Asn Leu Asn Val255 260 265GTT GGT AAC GAT TCC TTT GCT TGG CTT CCA CAA CTA GAA TAT TTC TTC 912Val Gly Asn Asp Ser Phe Ala Trp Leu Pro Gln Leu Glu Tyr Phe Phe270 275 280CTA GAG TAT AAT AAT ATA CAG CAT TTG TTT TCT CAC TCT TTG CAC GGG 960Leu Glu Tyr Asn Asn Ile Gln His Leu Phe Ser His Ser Leu His Gly285 290 295CTT TTC AAT GTG AGG TAC CTG AAT TTG AAA CGG TCT TTT ACT AAA CAA 1008Leu Phe Asn Val Arg Tyr Leu Asn Leu Lys Arg Ser Phe Thr Lys Gln300 305 310 315AGT ATT TCC CTT GCC TCA CTC CCC AAG ATT GAT GAT TTT TCT TTT CAG 1056Ser Ile Ser Leu Ala Ser Leu Pro Lys Ile Asp Asp Phe Ser Phe Gln320 325 330TGG CTA AAA TGT TTG GAG CAC CTT AAC ATG GAA GAT AAT GAT ATT CCA 1104Trp Leu Lys Cys Leu Glu His Leu Asn Met Glu Asp Asn Asp Ile Pro335 340 345GGC ATA AAA AGC AAT ATG TTC ACA GGA TTG ATA AAC CTG AAA TAC TTA 1152Gly Ile Lys Ser Asn Met Phe Thr Gly Leu Ile Asn Leu Lys Tyr Leu350 355 360AGT CTA TCC AAC TCC TTT ACA AGT TTG CGA ACT TTG ACA AAT GAA ACA 1200Ser Leu Ser Asn Ser Phe Thr Ser Leu Arg Thr Leu Thr Asn Glu Thr365 370 375TTT GTA TGA CTT GCT CAT TCT CCC TTA CAC ATA CTC AAC CTA ACC AAG 1248Phe Val Ser Leu Ala His Ser Pro Leu His Ile Leu Asn Leu Thr Lys380 385 390 395AAT AAA ATC TCA AAA ATA GAG AGT GAT GCT TTC TCT TGG TTG GGC CAC 1296Asn Lys Ile Ser Lys Ile Glu Ser Asp Ala Phe Ser Trp Leu Gly His400 405 410
CTA GAA GTA CTT GAC CTG GGC CTT AAT GAA ATT GGG CAA GAA CTC ACA 1344Leu Glu Val Leu Asp Leu Gly Leu Asn Glu Ile Gly Gln Glu Leu Thr415 420 425GGC CAG GAA TGG AGA GGT CTA GAA AAT ATT TTC GAA ATC TAT CTT TCC 1392Gly Gln Glu Trp Arg Gly Leu Glu Asn Ile Phe Glu Ile Tyr Leu Ser430 435 440TAC AAC AAG TAC CTG CAG CTG ACT AGG AAC TCC TTT GCC TTG GTC CCA 1440Tyr Asn Lys Tyr Leu Gln Leu Thr Arg Asn Ser Phe Ala Leu Val Pro445 450 455AGC CTT CAA CGA CTG ATG CTC CGA AGG GTG GCC CTT AAA AAT GTG GAT 1488Ser Leu Gln Arg Leu Met Leu Arg Arg Val Ala Leu Lys Asn Val Asp460 465 470 475AGC TCT CCT TCA CCA TTC CAG CCT CTT CGT AAC TTG ACC ATT CTG GAT 1536Ser Ser Pro Ser Pro Phe Gln Pro Leu Arg Ash Leu Thr Ile Leu Asp480 485 490CTA AGC AAC AAC AAC ATA GCC AAC ATA AAT GAT GAC ATG TTG GAG GGT 1584Leu Ser Asn Asn Asn Ile Ala Asn Ile Asn Asp Asp Met Leu Glu Gly495 500 505CTT GAG AAA CTA GAA ATT CTC GAT TTG CAG CAT AAC AAC TTA GCA CGG 1632Leu Glu Lys Leu Glu Ile Leu Asp Leu Gln His Asn Asn Leu Ala Arg510 515 520CTC TGG AAA CAC GCA AAC CCT GGT GGT CCC ATT TAT TTC CTA AAG GGT 1680Leu Trp Lys His Ala Asn Pro Gly Gly Pro Ile Tyr Phe Leu Lys Gly525 530 535CTG TCT CAC CTC CAC ATC CTT AAC TTG GAG TCC AAC GGC TTT GAC GAG 1728Leu Ser His Leu His Ile Leu Asn Leu Glu Ser Asn Gly Phe Asp Glu540 545 550 555ATC CCA GTT GAG GTC TTC AAG GAT TTA TTT GAA CTA AAG ATC ATC GAT 1776Ile Pro Val Glu Val Phe Lys Asp Leu Phe Glu Leu Lys Ile Ile Asp560 555 570TTA GGA TTG AAT AAT TTA AAC ACA CTT CCA GCA TCT GTC TTT AAT AAT 1824Leu Gly Leu Asn Asn Leu Asn Thr Leu Pro Ala Ser Val Phe Asn Asn575 580 585CAG GTG TCT CTA AAG TCA TTG AAC CTT CAG AAG AAT CTC ATA ACA TCC 1872Gln Val Ser Leu Lys Ser Leu Asn Leu Gln Lys Asn Leu Ile Thr Ser590 595 600GTT GAG AAG AAG GTT TTC GGG CCA GCT TTC AGG AAC CTG ACT GAG TTA 1920Val Glu Lys Lys Val Phe Gly Pro Ala Phe Arg Asn Leu Thr Glu Leu605 610 615
GAT ATG CGC TTT AAT CCC TTT GAT TGC ACG TGT GAA AGT ATT GCC TGG 1968Asp Met Arg Phe Asn Pro Phe Asp Cys Thr Cys Glu Ser Ile Ala Trp620 625 630 635TTT GTT AAT TGG ATT AAC GAG ACC CAT ACC AAC ATC CCT GAG CTG TCA 2016Phe Val Asn Trp Ile Asn Glu Thr His Thr Asn Ile Pro Glu Leu Ser640 645 650AGC CAC TAC CTT TGC AAC ACT CCA CCT CAC TAT CAT GGG TTC CCA GTG 2064Ser His Tyr Leu Cys Asn Thr Pro Pro His Tyr His Gly Phe Pro Val655 660 665AGA CTT TTT GAT ACA TCA TCT TGC AAA GAC AGT GCC CCC TTT GAA CTC 2112Arg Leu Phe Asp Thr Ser Ser Cys Lys Asp Ser Ala Pro Phe Glu Leu670 675 680TTT TTC ATG ATC AAT ACC AGT ATC CTG TTG ATT TTT ATC TTT ATT GTA 2160Phe Phe Met Ile Asn Thr Ser Ile Leu Leu Ile Phe Ile Phe Ile Val685 690 695CTT CTC ATC CAC TTT GAG GGC TGG AGG ATA TCT TTT TAT TGG AAT GTT 2208Leu Leu Ile His Phe Glu Gly Trp Arg Ile Ser Phe Tyr Trp Asn Val700 705 710 715TCA GTA CAT CGA GTT CTT GGT TTC AAA GAA ATA GAC AGA CAG ACA GAA 2256Ser Val His Arg Val Leu Gly Phe Lys Glu Ile Asp Arg Gln Thr Glu720 725 730CAG TTT GAA TAT GCA GCA TAT ATA ATT CAT GCC TAT AAA GAT AAG GAT 2304Gln Phe Glu Tyr Ala Ala Tyr Ile Ile His Ala Tyr Lys Asp Lys Asp735 740 745TGG GTC TGG GAA CAT TTC TCT TCA ATG GAA AAG GAA GAC CAA TCT CTC 2352Trp Val Trp Glu His Phe Ser Ser Met Glu Lys Glu Asp Gln Ser Leu750 755 760AAA TTT TGT CTG GAA GAA AGG GAC TTT GAG GCG GGT GTT TTT GAA CTA 2400Lys Phe Cys Leu Glu Glu Arg Asp Phe Glu Ala Gly Val Phe Glu Leu765 770 775GAA GCA ATT GTT AAC AGC ATC AAA AGA AGC AGA AAA ATT ATT TTT GTT 2448Glu Ala Ile Val Asn Ser Ile Lys Arg Ser Arg Lys Ile Ile Phe Val780 785 790 795ATA ACA CAC CAT CTA TTA AAA GAC CCA TTA TGC AAA AGA TTC AAG GTA 2496Ile Thr His His Leu Leu Lys Asp Pro Leu Cys Lys Arg Phe Lys Val800 805 810CAT CAT GCA GTT CAA CAA GCT ATT GAA CAA AAT CTG GAT TCC ATT ATA 2544His His Ala Val Gln Gln Ala Ile Glu Gln Asn Leu Asp Ser Ile Ile815 820 825TTG GTT TTC CTT GAG GAG ATT CCA GAT TAT AAA CTG AAC CAT GCA CTC 2592Leu Val Phe Leu Glu Glu Ile Pro Asp Tyr Lys Leu Asn His Ala Leu830 835 840
TGT TTG CGA AGA GGA ATG TTT AAA TCT CAC TGC ATC TTG AAC TGG CCA 2640Cys Leu Arg Arg Gly Met Phe Lys Ser His Cys Ile Leu Asn Trp Pro845 850 855GTT CAG AAA GAA CGG ATA GGT GCC TTT CGT CAT AAA TTG CAA GTA GCA 2688Val Gln Lys Glu Arg Ile Gly Ala Phe Arg His Lys Leu Gln Val Ala860 865 870 875CTT GGA TCC AAA AAC TCT GTA CAT TAA 2715Leu Gly Ser Lys Asn Ser Val His880MRQTLPCIYFWGGLLPFGMLCASSTTKCTVSHEVADCSHLKLTQVPDDLPTNITVLNLTHNQLRRLPAANFTRYSQLTSLDVGFNTISKLEPELCQKLPMLKVLNLQHNELSQLSDKTFAFCTNLTELHLMSNSIQKIKNNPFVKQKNLITLDLSHMGLSSTKLGTQVQLENLQELLLSNNKIQALKSEELDIFANSSLKKLELSSNQIKEFSPGCFHAIGRLFGLFLNNVQLGPSLTEKLCLELANTSIRNLSLSNSQLSTTSNTTFLGLKWTNLTMLDLSYNNLNVVGNDSFAWLPQLEYFFLEYNNIQHLPSHSLHGLFNVRYLNLKRSFTKQSISLASLPKIDDFSFQWLKCLEHLNMEDNDIPGIKSNMFTGLINLKYLSLSNSFTSLRTLTNETFVSLAHSPLHILNLTKNKISKIESDAFSWLGHLEVLDLGLNEIGQELTGQEWRGLENIFEIYLSYNKYLQLTRNSFALVPSLQRLMLRRVALKNVDSSPSPFQPLRNLTILDLSNNNIANINDDMLEGLEKLEILDLQHNNLARLWKHANPGGPIYFLKGLSHLHILNLESNGFDEIPVEVFKDLFELKIIDLGLNNLNTLPASVFNNQVSLKSLNLQKNLITSVEKKVFGPAFRNLTELDMRFNPFDCTCESIAWFVNWINETHTNIPELSSHYLCNTPPHYHGFPVRLFDTSSCKDSAPFELFFMINTSILLIFIFIVLLIHFEGWRISFYWNVSVHRVLGFKEIDRQTEQFEYAAYIIHAYKDKDWVWEHFSSMEKEDQSLKFCLEERDPEAGVFELEAIVNSIKRSRKIIFVITHHLLKDPLCKRFKVHHAVQQAIEQNLDSIILVFLEEIPDYKLNHALCLRRGMFKSHCILNWPVQKERIGAFRHKLQVALGSKNSVH
表4诸如灵长类动物或人等哺乳动物的DNAX Toll样受体4(DTLR4)的核苷酸序列和氨基酸序列(见SEQ ID NO7和8)。
ATG GAG CTG AAT TTC TAC AAA ATC CCC GAC AAC CTC CCC TTC TCA ACC 48Met Glu Leu Asn Phe Tyr Lys Ile Pro Asp Asn Leu Pro Phe Ser Thr1 5 10 15AAG AAC CTG GAC CTG AGC TTT AAT CCC CTG AGG CAT TTA GGC AGC TAT 96Lys Asn Leu Asp Leu Ser Phe Asn Pro Leu Arg His Leu Gly Ser Tyr20 25 30AGC TTC TTC AGT TTC CCA GAA CTG CAG GTG CTG GAT TTA TCC AGG TGT 144Ser Phe Phe Ser Phe Pro Glu Leu Gln Val Leu Asp Leu Ser Arg Cys35 40 45GAA ATC CAG ACA ATT GAA GAT GGG GCA TAT CAG AGC CTA AGC CAC CTC 192Glu Ile Gln Thr Ile Glu Asp Gly Ala Tyr Gln Ser Leu Ser His Leu50 55 60TCT ACC TTA ATA TTG ACA GGA AAC CCC ATC CAG AGT TTA GCC CTG GGA 240Ser Thr Leu Ile Leu Thr Gly Asn Pro Ile Gln Ser Leu Ala Leu Gly65 70 75 80GCC TTT TCT GGA CTA TCA AGT TTA CAG AAG CTG GTG GCT GTG GAG ACA 288Ala Phe Ser Gly Leu Ser Ser Leu Gln Lys Leu Val Ala Val Glu Thr85 90 95AAT CTA GCA TCT CTA GAG AAC TTC CCC ATT GGA CAT CTC AAA ACT TTG 336Asn Leu Ala Ser Leu Glu Asn Phe Pro Ile Gly His Leu Lys Thr Leu100 105 110AAA GAA CTT AAT GTG GCT CAC AAT CTT ATC CAA TCT TTC AAA TTA CCT 384Lys Glu Leu Asn Val Ala His Asn Leu Ile Gln Ser Phe Lys Leu Pro115 120 125GAG TAT TTT TCT AAT CTG ACC AAT CTA GAG CAC TTG GAC CTT TCC AGC 432Glu Tyr Phe Ser Asn Leu Thr Asn Leu Glu His Leu Asp Leu Ser Ser130 135 140AAC AAG ATT CAA AGT ATT TAT TGC ACA GAC TTG CGG GTT CTA CAT CAA 480Asn Lys Ile Gln Ser Ile Tyr Cys Thr Asp Leu Arg Val Leu His Gln145 150 155 160ATG CCC CTA CTC AAT CTC TCT TTA GAC CTG TCC CTG AAC CCT ATG AAC 528Met Pro Leu Leu Asn Leu Ser Leu Asp Leu Ser Leu Asn Pro Met Asn165 170 175TTT ATC CAA CCA GGT GCA TTT AAA GAA ATT AGG CTT CAT AAG CTG ACT 576Phe Ile Gln Pro Gly Ala Phe Lys Glu Ile Arg Leu His Lys Leu Thr180 185 190TTA AGA AAT AAT TTT GAT AGT TTA AAT GTA ATG AAA ACT TGT ATT CAA 624Leu Arg Asn Asn Phe Asp Ser Leu Asn Val Met Lys Thr Cys Ile Gln195 200 205
GGT CTG GCT GGT TTA GAA GTC CAT CGT TTG GIT CTG GGA GAA TTT AGA672Gly Leu Ala Gly Leu Glu Val His Arg Leu Val Leu Gly Glu Phe Arg210 215 220AAT GAA GGA AAC TTG GAA AAG TTT GAC AAA TCT GCT CTA GAG GGC CTG720Asn Glu Gly Asn Lau Glu Lys Phe Asp Lys Ser Ala Leu Glu Gly Leu225 230 235 240TGC AAT TTG ACC ATT GAA GAA TTC CGA TTA GCA TAC TTA GAC TAC TAC768Cys Asn Leu Thr Ile Glu Glu Phe Arg Leu Ala Tyr Leu Asp Tyr Tyr245 250 255CTC GAT GAT ATT ATT GAC TTA TTT AAT TGT TTG ACA AAT GTT TCT TCA816Leu Asp Asp Ile Ile Asp Leu Phe Asn Cys Leu Thr Asn Val Ser Ser260 265 270TTT TCC CTG GTG AGT GTG ACT ATT GAA AGG GTA AAA GAC TTT TCT TAT864Phe Ser Leu Val Ser Val Thr Ile Glu Arg Val Lys Asp Phe Ser Tyr275 280 285AAT TTC GGA TGG CAA CAT TTA GAA TTA GTT AAC TGT AAA TTT GGA CAG912Asn Phe Gly Trp Gln His Leu Glu Leu Val Asn Cys Lys Phe Gly Gln290 295 300TTT CCC ACA TTG AAA CTC AAA TCT CTC AAA AGG CTT ACT TTC ACT TCC960Phe Pro Thr Leu Lys Leu Lys Ser Leu Lys Arg Leu Thr Phe Thr Ser305 310 315 320AAC AAA GGT GGG AAT GCT TTT TCA GAA GTT GAT CTA CCA AGC CTT GAG 1008Asn Lys Gly Gly Asn Ala Phe Ser Glu Val Asp Leu Pro Ser Leu Glu325 330 335TTT CTA GAT CTC AGT AGA AAT GGC TTG AGT TTC AAA GGT TGC TGT TCT 1056Phe Leu Asp Leu Ser Arg Asn Gly Leu Ser Phe Lys Gly Cys Cys Ser340 345 350CAA AGT GAT TTT GGG ACA ACC AGC CTA AAG TAT TTA GAT CTG AGC TTC 1104Gln Ser Asp Phe Gly Thr Thr Ser Leu Lys Tyr Leu Asp Leu Ser Phe355 360 365AAT GGT GTT ATT ACC ATG AGT TCA AAC TTC TTG GGC TTA GAA CAA CTA 1152Asn Gly Val Ile Thr Met Ser Ser Asn Phe Leu Gly Leu Glu Gln Leu370 375 380GAA CAT CTG GAT TTC CAG CAT TCC AAT TTG AAA CAA ATG AGT GAG TTT 1200Glu His Leu Asp Phe Gln His Ser Asn Leu Lys Gln Met Ser Glu Phe385 390 395 400TCA GTA TTC CTA TCA CTC AGA AAC CTC ATT TAC CTT GAC ATT TCT CAT 1248Ser Val Phe Leu Ser Leu Arg Asn Leu Ile Tyr Leu Asp Ile Ser His405 410 415ACT CAC ACC AGA GTT GCT TTC AAT GGC ATC TTC AAT GGC TTG TCC AGT 1296Thr His Thr Arg Val Ala Phe Asn Gly Ile Phe Asn Gly Leu Ser Ser420 426 430
CTC GAA GTC TTG AAA ATG GCT GGC AAT TCT TTC CAG GAA AAC TTC CTT1344Leu Glu Val Leu Lys Met Ala Gly Asn Ser Phe Gln Glu Asn Phe Leu435 440 445CCA GAT ATC TTC ACA GAG CTG AGA AAC TTG ACC TTC CTG GAC CTC TCT1392Pro Asp Ile Phe Thr Glu Leu Arg Asn Leu Thr Phe Leu Asp Leu Ser450 455 460CAG TGT CAA CTG GAG CAG TTG TCT CCA ACA GCA TTT AAC TCA CTC TCC1440Gln Cys Gln Leu Glu Gln Leu Ser Pro Thr Ala Phe Asn Ser Leu Ser465 470 475 480AGT CTT CAG GTA CTA AAT ATG AGC CAC AAC AAC TTC TTT TCA TTG GAT1488Ser Leu Gln Val Leu Asn Met Ser His Asn Asn Phe Phe Ser Leu Asp485 490 495ACG TTT CCT TAT AAG TGT CTG AAC TCC CTC CAG GTT CTT GAT TAC AGT1536Thr Phe Pro Tyr Lys Cys Leu Asn Ser Leu Gln Val Leu Asp Tyr Ser500 505 510CTC AAT CAC ATA ATG ACT TCC AAA AAA CAG GAA CTA CAG CAT TTT CCA1584Leu Asn His Ile Met Thr Ser Lys Lys Gln Glu Leu Gln His Phe Pro515 520 525AGT AGT CTA GCT TTC TTA AAT CTT ACT CAG AAT GAC TTT GCT TGT ACT1632Ser Ser Leu Ala Phe Leu Asn Leu Thr Gln Asn Asp Phe Ala Cys Thr530 535 540TGT GAA CAC CAG AGT TTC CTG CAA TGG ATC AAG GAC CAG AGG CAG CTC1680Cys Glu His Gln Ser Phe Leu Gln Trp Ile Lys Asp Gln Arg Gln Leu545 550 555 560TTG GTG GAA GTT GAA CGA ATG GAA TGT GCA ACA CCT TCA GAT AAG CAG1728Leu Val Glu Val Glu Arg Met Glu Cys Ala Thr Pro Ser Asp Lys Gln565 570 575GGC ATG CCT GTG CTG AGT TTG AAT ATC ACC TGT CAG ATG AAT AAG ACC1776Gly Met Pro Val Leu Ser Leu Asn Ile Thr Cys Gln Met Asn Lys Thr580 585 590ATC ATT GGT GTG TCG GTC CTC AGT GTG CTT GTA GTA TCT GTT GTA GCA1824Ile Ile Gly Val Ser Val Leu Ser Val Leu Val Val Ser Val Val Ala595 600 605GTT CTG GTC TAT AAG TTC TAT TTT CAC CTG ATG CTT CTT GCT GGC TGC1872Val Leu Val Tyr Lys Phe Tyr Phe His Leu Met Leu Leu Ala Gly Cys610 615 620ATA AAG TAT GGT AGA GGT GAA AAC ATC TAT GAT GCC TTT GTT ATC TAC1920Ile Lys Tyr Gly Arg Gly Glu Asn Ile Tyr Asp Ala Phe Val Ile Tyr625 630 635 640
TCA AGC CAG GAT GAG GAC TGG GTA AGG AAT GAG CTA GTA AAG AAT TTA 1968Ser Ser Gln Asp Glu Asp Trp Val Arg Asn Glu Leu Val Lys Asn Leu645 650 655GAA GAA GGG GTG CCT CCA TTT CAG CTC TGC CTT CAC TAC AGA GAC TTT 2016Glu Glu Gly Val Pro Pro Phe Gln Leu Cys Leu His Tyr Arg Asp Phe660 665 670ATT CCC GGT GTG GCC ATT GCT GCC AAC ATC ATC CAT GAA GGT TTC CAT 2064Ile Pro Gly Val Ala Ile Ala Ala Asn Ile Ile His Glu Gly Phe His675 680 685AAA AGC CGA AAG GTG ATT GTT GTG GTG TCC CAG CAC TTC ATC CAG AGC 2112Lys Ser Arg Lys Val Ile Val Val Val Ser Gln His Phe Ile Gln Ser690 695 700CGC TGG TGT ATC TTT GAA TAT GAG ATT GCT CAG ACC TGG CAG TTT CTG 2160Arg Trp Cys Ile Phe Glu Tyr Glu Ile Ala Gln Thr Trp Gln Phe Leu705 710 715 720AGC AGT CGT GCT GGT ATC ATC TTC ATT GTC CTG CAG AAG GTG GAG AAG 2208Ser Ser Arg Ala Gly Ile Ile Phe Ile Val Leu Gln Lys Val Glu Lys725 730 735ACC CTG CTC AGG CAG CAG GTG GAG CTG TAC CGC CTT CTC AGC AGG AAC 2256Thr Leu Leu Arg Gln Gln Val Glu Leu Tyr Arg Leu Leu Ser Arg Asn740 745 750ACT TAC CTG GAG TGG GAG GAC AGT GTC CTG GGG CGG CAC ATC TTC TGG 2304Thr Tyr Leu Glu Trp Glu Asp Ser Val Leu Gly Arg His Ile Phe Trp755 760 765AGA CGA CTC AGA AAA GCC CTG CTG GAT GGT AAA TCA TGG AAT CCA GAA 2352Arg Arg Leu Arg Lys Ala Leu Leu Asp Gly Lys Ser Trp Asn Pro Glu770 775 780GGA ACA GTG GGT ACA GGA TGC AAT TGG CAG GAA GCA ACA TCT ATC 2397Gly Thr Val Gly Thr Gly Cys Asn Trp Gln Glu Ala Thr Ser Ile785 790 795TGA 2400MELNFYKIPDNLPFSTKNLDLSFNPLRHLGSYSFFSFPELQVLDLSRCEIQTIEDGAYQSLSHLSTLILTGNPIQSLALGAFSGLSSLQKLVAVETNLASLENFPIGHLKTLKELNVAHNLIQSFKLPEYFSNLTNLEHLDLSSNKIQSIYCTDLRVLHQMPLLNLSLDLSLNPMNFIQPGAFKEIRLHKLTLRNNFDSLNVMKTCIQGLAGLEVHRLVLGEFRNEGNLEKFDKSALEGLCNLTIEEFRLAYLDYYLDDIIDLFNCLTNVSSFSLVSVTIERVKDESYNFGWQHLELVNCKFGQFPTLKLKSLKRLTFTSNKGGNAFSEVDLPSLEFLDLSRNGLSFKGCCSQSDFGTTSLKYLDLSFNGVITMSSNFLGLEQLEHLDFQHSNLKQMSEFSVFLSLRNLIYLDISHTHTRYAFNGIFNGLSSLEVLKMAGNSFQENFLPDIFTELRNLTFLDLSQCQLEQLSPTAFNSLSSLQVLNMSHNNFFSLDTFPYKCLNSLQVLDYSLNHIMTSKKQELQHFPSSLAFLNLTQNDFACTCEHQSFLQWIKDQRQLLVEVERMECATPSDKQGMPVLSLNITCQMNKTIIGVSVLSVLVVSVVAVLVYKFYFHLMLLAGCIKYGRGENIYDAFVIYSSQDEDWVRNELVKNLEEGVPPFQLCLHYRDFIPGVAIAANIIHEGFHKSRKVIVVVSQHFIQSRWCIFEYEIAQTWQFLSSRAGIIFIVLQKVEKTLLRQQVELYRLLSRNTYLEWEDSVLGRHIFWRRLRKALLDGKSWNPEGTVGTGCNWQEATSI
诸如人等灵长类动物的DTLR4的附加序列(SEQ ID NQ25和26)；注意用A表示的第81、3144、3205和3563位核苷酸的每个都可以是A、C、G或T；用G表叔的第3132、3532、3538和3553位核苷酸的每个都可以是G或T；用A表示的第3638位核苷酸可以是A或T；并且用C表示的第3677、3685和3736位核苷酸的每个都可以是A或CAAAATACTCC CTTGCCTCAA AAACTGCTCG GTCAAACGGT GATAGCAAAC CACGCATTCA 60CAGGGCCACT GCTGCTCACA AAACCAGTGA GGATGATGCC AGGATG ATG TCT GCC 115Met Ser Ala-22 -20TCG CGC CTG GCT GGG ACT CTG ATC CCA GCC ATG GCC TTC CTC TCC TGC163Ser Arg Leu Ala Gly Thr Leu Ile Pro Ala Met Ala Phe Leu Ser Cys-15 -10 -5GTG AGA CCA GAA AGC TGG GAG CCC TGC GTG GAG GTT CCT AAT ATT ACT211Val Arg Pro Glu Ser Trp Glu Pro Cys Val Glu Val Pro Asn Ile Thr1 5 10TAT CAA TGC ATG GAG CTG AAT TTC TAC AAA ATC CCC GAC AAC CTC CCC259Tyr Gln Cys Met Glu Leu Asn Phe Tyr Lys Ile Pro Asp Asn Leu Pro15 20 25TTC TCA ACC AAG AAC CTG GAC CTG AGC TTT AAT CCC CTG AGG CAT TTA307Phe Ser Thr Lys Asn Leu Asp Leu Ser Phe Asn Pro Leu Arg His Leu30 35 40 45GGC AGC TAT AGC TTC TTC AGT TTC CCA GAA CTG CAG GTG CTG GAT TTA355Gly Ser Tyr Ser Phe Phe Ser Phe Pro Glu Leu Gln Val Leu Asp Leu50 55 60TCC AGG TGT GAA ATC CAG ACA ATT GAA GAT GGG GCA TAT CAG AGC CTA403Ser Arg Cys Glu Ile Gln Thr Ile Glu Asp Gly Ala Tyr Gln Ser Leu65 70 75AGC CAC CTC TCT ACC TTA ATA TTG ACA GGA AAC CCC ATC CAG AGT TTA451Ser His Leu Ser Thr Leu Ile Leu Thr Gly Asn Pro Ile Gln Ser Leu80 85 90GCC CTG GGA GCC TTT TCT GGA CTA TCA AGT TTA CAG AAG CTG GTG GCT499Ala Leu Gly Ala Phe Ser Gly Leu Ser Ser Leu Gln Lys Leu Val Ala95 100 105GTG GAG ACA AAT CTA GCA TCT CTA GAG AAC TTC CCC ATT GGA CAT CTC547Val Glu Thr Asn Leu Ala Ser Leu Glu Asn Phe Pro Ile Gly His Leu110 115 220 125AAA ACT TTG AAA GAA CTT AAT GTG GCT CAC AAT CTT ATC CAA TCT TTC595Lys Thr Leu Lys Glu Leu Asn Val Ala His Asn Leu Ile Gln Ser Phe130 135 140AAA TTA CCT GAG TAT TTT TCT AAT CTG ACC AAT CTA GAG CAC TTG GAC643Lys Leu Pro Glu Tyr Phe Ser Asn Leu Thr Asn Leu Glu His Leu Asp145 150 155
CTT TCC AGC AAC AAG ATT CAA AGT ATT TAT TGC ACA GAC TTG CGG GTT691Leu Ser Ser Asn Lys Ile Gln Ser Ile Tyr Cys Thr Asp Leu Arg Val160 165 170CTA CAT CAA ATG CCC CTA CTC AAT CTC TCT TTA GAC CTG TCC CTG AAC739Leu His Gln Met Pro Leu Leu Asn Leu Ser Leu Asp Leu Ser Leu Asn175 180 185CCT ATG AAC TTT ATC CAA CCA GGT GCA TTT AAA GAA ATT AGG CTT CAT787Pro Met Asn Phe Ile Gln Pro Gly Ala Phe Lys Glu Ile Arg Leu His190 195 200 205AAG CTG ACT TTA AGA AAT AAT TTT GAT AGT TTA AAT GTA ATG AAA ACT835Lys Leu Thr Leu Arg Asn Asn Phe Asp Ser Leu Asn Val Met Lys Thr210 215 220TGT ATT CAA GGT CTG GCT GGT TTA GAA GTC CAT CGT TTG GTT CTG GGA883Cys Ile Gln Gly Leu Ala Gly Leu Glu Val His Arg Leu Val Leu Gly225 230 235GAA TTT AGA AAT GAA GGA AAC TTG GAA AAG TTT GAC AAA TCT GCT CTA931Glu Phe Arg Asn Glu Gly Asn Leu Glu Lys Phe Asp Lys Ser Ala Leu240 245 250GAG GGC CTG TGC AAT TTG ACC ATT GAA GAA TTC CGA TTA GCA TAC TTA979Glu Gly Leu Cys Asn Leu Thr Ile Glu Glu Phe Arg Leu Ala Tyr Leu255 260 265GAC TAC TAC CTC GAT GAT ATT ATT GAC TTA TTT AAT TGT TTG ACA AAT 1027Asp Tyr Tyr Leu Asp Asp Ile Ile Asp Leu Phe Asn Cys Leu Thr Asn270 275 280 285GTT TCT TCA TTT TCC CTG GTG AGT GTG ACT ATT GAA AGG GTA AAA GAC 1075Val Ser Ser Phe Ser Leu Val Ser Val Thr Ile Glu Arg Val Lys Asp290 295 300TTT TCT TAT AAT TTC GGA TGG CAA CAT TTA GAA TTA GTT AAC TGT AAA 1123Phe Ser Tyr Asn Phe Gly Trp Gln His Leu Glu Leu Val Asn Cys Lys305 310 315TTT GGA CAG TTT CCC ACA TTG AAA CTC AAA TCT CTC AAA AGG CTT ACT 1171Phe Gly Gln Phe Pro Thr Leu Lys Leu Lys Ser Leu Lys Arg Leu Thr320 325 330TTC ACT TCC AAC AAA GGT GGG AAT GCT TTT TCA GAA GTT GAT CTA CCA 1219Phe Thr Ser Asn Lys Gly Gly Asn Ala Phe Ser Glu Val Asp Leu Pro335 340 345AGC CTT GAG TTT CTA GAT CTC AGT AGA AAT GGC TTG AGT TTC AAA GGT 1267Ser Leu Glu Phe Leu Asp Leu Ser Arg Asn Gly Leu Ser Phe Lys Gly350 355 360 365
TGC TGT TCT CAA AGT GAT TTT GGG ACA ACC AGC CTA AAG TAT TTA GAT 1315Cys Cys Ser Gln Ser Asp Phe Gly Thr Thr Ser Leu Lys Tyr Leu Asp370 375 380CTG AGC TTC AAT GGT GTT ATT ACC ATG AGT TCA AAC TTC TTG GGC TTA 1363Leu Ser Phe Asn Gly Val Ile Thr Met Ser Ser Asn Phe Leu Gly Leu385 390 395GAA CAA CTA GAA CAT CTG GAT TTC CAG CAT TCC AAT TTG AAA CAA ATG 1411Glu Gln Leu Glu His Leu Asp Phe Gln His Ser Asn Leu Lys Gln Met400 405 410AGT GAG TTT TCA GTA TTC CTA TCA CTC AGA AAC CTC ATT TAC CTT GAC 1459Ser Glu Phe Ser Val Phe Leu Ser Leu Arg Asn Leu Ile Tyr Leu Asp415 420 425ATT TCT CAT ACT CAC ACC AGA GTT GCT TTC AAT GGC ATC TTC AAT GGC 1507Ile Ser His Thr His Thr Arg Val Als Phe Asn Gly Ile Phe Asn Gly430 435 440 445TTG TCC AGT CTC GAA GTC TTG AAA ATG GCT GGC AAT TCT TTC CAG GAA 1555Leu Ser Ser Leu Glu Val Leu Lys Met Ala Gly Asn Ser Phe Gln Glu450 455 460AAC TTC CTT CCA GAT ATC TTC ACA GAG CTG AGA AAC TTG ACC TTC CTG 1603Asn Phe Leu Pro Asp Ile Phe Thr Glu Leu Arg Asn Leu Thr Phe Leu465 470 475GAC CTC TCT CAG TGT CAA CTG GAG CAG TTG TCT CCA ACA GCA TTT AAC 1651Asp Leu Ser Gln Cys Gln Leu Glu Gln Leu Ser Pro Thr Ala Phe Asn480 485 490TCA CTC TCC AGT CTT CAG GTA CTA AAT ATG AGC CAC AAC AAC TTC TTT 1699Ser Leu Ser Ser Leu Gln Val Leu Asn Met Ser His Asn Asn Phe Phe495 500 505TCA TTG GAT ACG TTT CCT TAT AAG TGT CTG AAC TCC CTC CAG GTT CTT 1747Ser Leu Asp Thr Phe Pro Tyr Lys Cys Leu Asn Ser Leu Gln Val Leu510 515 520 525GAT TAC AGT CTC AAT CAC ATA ATG ACT TCC AAA AAA CAG GAA CTA CAG 1795Asp Tyr Ser Leu Asn His Ile Met Thr Ser Lys Lys Gln Glu Leu Gln530 535 540CAT TTT CCA AGT AGT CTA GCT TTC TTA AAT CTT ACT CAG AAT GAC TTT 1843His Phe Pro Ser Ser Leu Ala Phe Leu Asn Leu Thr Gln Asn Asp Phe545 550 555GCT TGT ACT TGT GAA CAC CAG AGT TTC CTG CAA TGG ATC AAG GAC CAG 1891Ala Cys Thr Cys Glu His Gln Ser Phe Leu Gln Trp Ile Lys Asp Gln560 565 570AGG CAG CTC TTG GTG GAA GTT GAA CGA ATG GAA TGT GCA ACA CCT TCA 1939Arg Gln Leu Leu Val Glu Val Glu Arg Met Glu Cys Ala Thr Pro Ser575 580 585
GAT AAG CAG GGC ATG CCT GTG CTG AGT TTG AAT ATC ACC TGT CAG ATG 1987Asp Lys Gln Gly Met Pro Val Leu Ser Leu Asn Ile Thr Cys Gln Met590 595 600 605AAT AAG ACC ATC ATT GGT GTG TCG GTC CTC AGT GTG CTT GTA GTA TCT 2035Asn Lys Thr Ile Ile Gly Val Ser Val Leu Ser Val Leu Val Val Ser610 615 620GTT GTA GCA GTT CTG GTC TAT AAG TTC TAT TTT CAC CTG ATG CTT CTT 2083Val Val Ala Val Leu Val Tyr Lys Phe Tyr Phe His Leu Met Leu Leu625 630 635GCT GGC TGC ATA AAG TAT GGT AGA GGT GAA AAC ATC TAT GAT GCC TTT 2131Ala Gly Cys Ile Lys Tyr Gly Arg Gly Glu Asn Ile Tyr Asp Ala Phe640 645 650GTT ATC TAC TCA AGC CAG GAT GAG GAC TGG GTA AGG AAT GAG CTA GTA 2179Val Ile Tyr Ser Ser Gln Asp Glu Asp Trp Val Arg Asn Glu Leu Val655 660 665AAG AAT TTA GAA GAA GGG GTG CCT CCA TTT CAG CTC TGC CTT CAC TAC 2227Lys Asn Leu Glu Glu Gly Val Pro Pro Phe Gln Leu Cys Leu His Tyr670 675 680 685AGA GAC TTT ATT CCC GGT GTG GCC ATT GCT GCC AAC ATC ATC CAT GAA 2275Arg Asp Phe Ile Pro Gly Val Ala Ile Ala Ala Asn Ile Ile His Glu690 695 700GGT TTC CAT AAA AGC CGA AAG GTG ATT GTT GTG GTG TCC CAG CAC TTC 2323Gly Phs His Lys Ser Arg Lys Val Ile Val Val Val Ser Gln His Phe705 710 715ATC CAG AGC CGC TGG TGT ATC TTT GAA TAT GAG ATT GCT CAG ACC TGG 2371Ile Gln Ser Arg Trp Cys Ile Phe Glu Tyr Glu Ile Ala Gln Thr Trp720 725 730CAG TTT CTG AGC AGT CGT GCT GGT ATC ATC TTC ATT GTC CTG CAG AAG 2419Gln Phe Leu Ser Ser Arg Ala Gly Ile Ile Phe Ile Val Leu Gln Lys735 740 745GTG GAG AAG ACC CTG CTC AGG CAG CAG GTG GAG CTG TAC CGC CTT CTC 2467Val Glu Lys Thr Leu Leu Arg Gln Gln Val Glu Leu Tyr Arg Leu Leu750 755 760 765AGC AGG AAC ACT TAC CTG GAG TGG GAG GAC AGT GTC CTG GGG CGG CAC 2515Ser Arg Asn Thr Tyr Leu Glu Trp Glu Asp Ser Val Leu Gly Arg His770 775 780ATC TTC TGG AGA CGA CTC AGA AAA GCC CTG CTG GAT GGT AAA TCA TGG 2563Ile Phe Trp Arg Arg Leu Arg Lys Ala Leu Leu Asp Gly Lys Ser Trp785 790 795
AAT CCA GAA GGA ACA GTG GGT ACA GGA TGC AAT TGG CAG GAA GCA ACA 2611Asn Pro Glu Gly Thr Val Gly Thr Gly Cys Asn Trp Gln Glu Ala Thr800 805 810TCT ATC TGAAGAGGAA AAATAAAAAC CTCCTGAGGC ATTTCTTGCC CAGCTGGGTC2667Ser Ile815CAACACTTGT TCAGTTAATA AGTATTAAAT GCTGCCACAT GTCAGGCCTT ATGCTAAGGG 2727TGAGTAATTC CATGGTGCAC TAGATATGCA GGGCTGCTAA TCTCAAGGAG CTTCCAGTGC 2787AGAGGGAATA AATGCTAGAC TAAAATACAG AGTCTTCCAG GTGGGCATTT CAACCAACTC 2847AGTCAAGGAA CCCATGACAA AGAAAGTCAT TTCAACTCTT ACCTCATCAA GTTGAATAAA 2907GACAGAGAAA ACAGAAAGAG ACATTGTTCT TTTCCTGAGT CTTTTGAATG GAAATTGTAT 2967TATGTTATAG CCATCATAAA ACCATTTTGG TAGTTTTGAC TGAACTGGGT GTTCACTTTT 3027TCCTTTTTGA TTGAATACAA TTTAAATTCT ACTTGATGAC TGCAGTCGTC AAGGGGCTCC 3087TGATGCAAGA TGCCCCTTCC ATTTTAAGTC TGTCTCCTTA CAGAGGTTAA AGTCTAATGG 3147CTAATTCCTA AGGAAACCTG ATTAACACAT GCTCACAACC ATCCTGGTCA TTCTCGAACA 3207TGTTCTATTT TTTAACTAAT CACCCCTGAT ATATTTTTAT TTTTATATAT CCAGTTTTCA 3267TTTTTTTACG TCTTGCCTAT AAGCTAATAT CATAAATAAG GTTGTTTAAG ACGTGCTTCA 3327AATATCCATA TTAACCACTA TTTTTCAAGG AAGTATGGAA AAGTACACTC TGTCACTTTG 3387TCACTCGATG TCATTCCAAA GTTATTGCCT ACTAAGTAAT GACTGTCATG AAAGCAGCAT 3447TGAAATAATT TGTTTAAAGG GGGCACTCTT TTAAACGGGA AGAAAATTTC CGCTTCCTGG 3507TCTTATCATG GACAATTTGG GCTAGAGGCA GGAAGGAAGT GGGATGACCT CAGGAAGTCA 3567CCTTTTCTTG ATTCCAGAAA CATATGGGCT GATAAACCCG GGGTGACCTC ATGAAATGAG 3627TTGCAGCAGA AGTTTATTTT TTTCAGAACA AGTGATGTTT GATGGACCTC TGAATCTCTT 3687TAGGGAGACA CAGATGGCTG GGATCCCTCC CCTGTACCCT TCTCACTGCC AGGAGAACTA 3747CGTGTGAAGG TATTCAAGGC AGGGAGTATA CATTGCTGTT TCCTGTTGGG CAATGCTCCT 3807TGACCACATT TTGGGAAGAG TGGATGTTAT CATTGAGAAA ACAATGTGTC TGGAATTAAT 3867GGGGTTCTTA TAAAGAAGGT TCCCAGAAAA GAATGTTCAT TCCAGCTTCT TCAGGAAACA 3927GGAACATTCA AGGAAAAGGA CAATCAGGAT GTCATCAGGG AAATGAAAAT AAAAACCACA 3987ATGAGATATC ACCTTATACC AGGTAGATGG CTACTATAAA AAAATGAAGT GTCATCAAGG 4047ATATAGAGAA ATTGGAACCC TTCTTCACTG CTGGAGGGAA TGGAAAATGG TGTAGCCGTT 4107
ATGAAAAACA GTACGGAGGT TTCTCAAAAA TTAAAAATAG AACTGCTATA TGATCCAGCA4167ATCTCACTTC TGTATATATA CCCAAAATAA TTGAAATCAG AATTTCAAGA AAATATTTAC4227ACTCCCATGT TCATTGTGGC ACTCTTCACA ATCACTGTTT CCAAAGTTAT GGAAACAACC4287CAAATTTCCA TTGGAAAATA AATGGACAAA GGAAATGTGC ATATAACGTA CAATGGGGAT4347ATTATTCAGC CTAAAAAAAG GGGGGATCCT GTTATTTATG ACAACATGAA TAAACCCGGA4407GGCCATTATG CTATGTAAAA TGAGCAAGTA ACAGAAAGAC AAATACTGCC TGATTTCATT4467TATATGAGGT TCTAAAATAG TCAAACTCAT AGAAGCAGAG AATAGAACAG TGGTTCCTAG4527GGAAAAGGAG GAAGGGAGAA ATGAGGAAAT AGGGAGTTGT CTAATTGGTA TAAAATTATA4587GTATGCAAGA TGAATTAGCT CTAAAGATCA GCTGTATAGC AGAGTTCGTA TAATGAACAA4647TACTGTATTA TGCACTTAAC ATTTTGTTAA GAGGGTACCT CTCATGTTAA GTGTTCTTAC4707CATATACATA TACACAAGGA AGCTTTTGGA GGTGATGGAT ATATTTATTA CCTTGATTGT4767GGTGATGGTT TGACAGGTAT GTGACTATGT CTAAACTCAT CAAATTGTAT ACATTAAATA4827TATGCAGTTT TATAATATCA AAAAAAAAAA AAAAAAAAAA 4865MSASRLAGTLIPAMAFLSCVRPESWEPCVEVPNITYQCMELNFYKIPDNLPFSTKNLDLSFNPLRHLGSYSFFSFPELQVLDLSRCEIQTIEDGAYQSLSHLSTLILTGNPIQSLALGAFSGLSSLQKLVAVETNLASLENFPIGHLKTLKELNVAHNLIQSFKLPEYFSNLTNLEHLDLSSNKIQSIYCTDLRVLHQMPLLNLSLDLSLNPMNFIQPGAFKEIRLHKLTLRNNFDSLNVMKTCIQGLAGLEVHRLVLGEFRNEGNLEKFDKSALEGLCNLTIEEFRLAYLDYYLDDIIDLFNCLTNVSSFSLVSVTIERVKDFSYNFGWQHLELVNCKFGQFPTLKLKSLKRLTFTSNKGGNAFSEVDLPSLEFLDLSRNGLSFKGCCSQSDFGTTSLKYLDLSFNGVITMSSNFLGLEQLEHLDFQHSNLKQMSEFSVFLSLRNLIYLDISHTHTRVAFNGIFNGLSSLEVLKMAGNSFQENFLPDIFTELRNLTFLDLSQCQLEQLSPTAFNSLSSLQVLNMSHNNFFSLDTFPYKCLNSLQVLDYSLNHIMTSKKQELQHFPSSLAFLNLTQNDFACTCEHQSFLQWIKDQRQLLVEVERMECATPSDKQGMPVLSLNITCQMNKTIIGVSVLSVLVVSVVAVLVYKFYEHLMLLAGCIKYGRGENIYDAFVIYSSQDEDWVRNELVKNLEEGVPPFQLCLHYRDFIPGVAIAANIIHEGFHKSRKVIVVVSQHFIQSRWCIFEYEIAQTWQFLSSRAGIIFIVLQKVEKTLLRQQVELYRLLSRNTYLEWEDSVLGRHIFWRRLRKALLDGKSWNPEGTVGTGCNWQEATSI
表5诸如灵长类动物或人等哺乳动物的DNAX Toll样受体5(DTLR5)的部分核苷酸序列和氨基酸序列(见SEQ ID NO9和10)。
TGT TGG GAT GTT TTT GAG GGA CTT TCT CAT CTT CAA GTT CTG TAT TTG 48Cys Trp Asp Val Phe Glu Gly Leu Ser His Leu Gln Val Leu Tyr Leu1 5 10 15AAT CAT AAC TAT CTT AAT TCC CTT CCA CCA GGA GTA TTT AGC CAT CTG 96Asn His Asn Tyr Leu Asn Ser Leu Pro Pro Gly Val Phe Ser His Leu20 25 30ACT GCA TTA AGG GGA CTA AGC CTC AAC TCC AAC AGG CTG ACA GTT CTT 144Thr Ala Leu Arg Gly Leu Ser Leu Asn Ser Asn Arg Leu Thr Val Leu35 40 45TCT CAC AAT GAT TTA CCT GCT AAT TTA GAG ATC CTG GAC ATA TCC AGG 192Ser His Asn Asp Leu Pro Ala Asn Leu Glu Ile Leu Asp Ile Ser Arg50 55 60AAC CAG CTC CTA GCT CCT AAT CCT GAT GTA TTT GTA TCA CTT AGT GTC 240Asn Gln Leu Leu Ala Pro Asn Pro Asp Val Phe Val Ser Leu Ser Val65 70 75 80TTG GAT ATA ACT CAT AAC AAG TTC ATT TGT GAA TGT GAA CTT AGC ACT 288Leu Asp Ile Thr His Asn Lys Phe Ile Cys Glu Cys Glu Leu Ser Thr85 90 95TTT ATC AAT TGG CTT AAT CAC ACC AAT GTC ACT ATA GCT GGG CCT CCT 336Phe Ile Asn Trp Leu Asn His Thr Asn Val Thr Ile Ala Gly Pro Pro100 105 110GCA GAC ATA TAT TGT GTG TAC CCT GAC TCG TTC TCT GGG GTT TCC CTC 384Ala Asp Ile Tyr Cys Val Tyr Pro Asp Ser Phe Ser Gly Val Ser Leu115 120 125TTC TCT CTT TCC ACG GAA GGT TGT GAT GAA GAG GAA GTC TTA AAG TCC 432Phe Ser Leu Ser Thr Glu Gly Cys Asp Glu Glu Glu Val Leu Lys Ser130 135 140CTA AAG TTC TCC CTT TTC ATT GTA TGC ACT GTC ACT CTG ACT CTG TTC 480Leu Lys Phe Ser Leu Phe Ile Val Cys Thr Val Thr Leu Thr Leu Phe145 150 155 160CTC ATG ACC ATC CTC ACA GTC ACA AAG TTC CGG GGC TTC TGT TTT ATC 528Leu Met Thr Ile Leu Thr Val Thr Lys Phe Arg Gly Phe Cys Phe Ile165 170 175TGT TAT AAG ACA GCC CAG AGA CTG GTG TTC AAG GAC CAT CCC CAG GGC 576Cys Tyr Lys Thr Ala Gln Arg Leu Val Phe Lys Asp His Pro Gln Gly180 185 190ACA GAA CCT GAT ATG TAC AAA TAT GAT GCC TAT TTG TGC TTC AGC AGC 624Thr Glu Pro Asp Met Tyr Lys Tyr Asp Ala Tyr Leu Cys Phe Ser Ser195 200 205
AAA GAC TTC ACA TGG GTG CAG AAT GCT TTG CTC AAA CAC CTG GAC ACT 672Lys Asp Phe Thr Trp Val Gln Asn Ala Leu Leu Lys His Leu Asp Thr210 215 220CAA TAC AGT GAC CAA AAC AGA TTC AAC CTG TGC TTT GAA GAA AGA GAC 720Gln Tyr Ser Asp Gln Asn Arg Phe Asn Leu Cys Phe Glu Glu Arg Asp225 230 235 240TTT GTC CCA GGA GAA AAC CGC ATT GCC AAT ATC CAG GAT GCC ATC TGG 768Phe Val Pro Gly Glu Asn Arg Ile Ala Asn Ile Gln Asp Ala Ile Trp245 250 255AAC AGT AGA AAG ATC GTT TGT CTT GTG AGC AGA CAC TTC CTT AGA GAT 816Asn Ser Arg Lys Ile Val Cys Leu Val Ser Arg His Phe Leu Arg Asp260 265 270GGC TGG TGC CTT GAA GCC TTC AGT TAT GCC CAG GGC AGG TGC TTA TCT 864Gly Trp Cys Leu Glu Ala Phe Ser Tyr Ala Gln Gly Arg Cys Leu Ser275 280 285GAC CTT AAC AGT GCT CTC ATC ATG GTG GTG GTT GGG TCC TTG TCC CAG 912Asp Leu Asn Ser Ala Leu Ile Met Val Val Val Gly Ser Leu Ser Gln290 295 300TAC CAG TTG ATG AAA CAT CAA TCC ATC AGA GGC TTT GTA CAG AAA CAG 960Tyr Gln Leu Met Lys His Gln Ser Ile Arg Gly Phe Val Gln Lys Gln305 310 315 320CAG TAT TTG AGG TGG CCT GAG GAT CTC CAG GAT GTT GGC TGG TTT CTT1008Gln Tyr Leu Arg Trp Pro Glu Asp Leu Gln Asp Val Gly Trp Phe Leu323 330 335CAT AAA CTC TCT CAA CAG ATA CTA AAG AAA GAA AAG GAA AAG AAG AAA1056His Lys Leu Ser Gln Gln Ile Leu Lys Lys Glu Lys Glu Lys Lys Lys340 345 350GAC AAT AAC ATT CCG TTG CAA ACT GTA GCA ACC ATC TCC TAATCAAAGG 1105Asp Asn Asn Ile Pro Leu Gln Thr Val Ala Thr Ile Ser355 360 365AGCAATTTCC AACTTATCTC AAGCCACAAA TAACTCTTCA CTTTGTATTT GCACCAAGTT 1165ATCATTTTGG GGTCCTCTCT GGAGGTTTTT TTTTTCTTTT TGCTACTATG AAAACAACAT 1225AAATCTCTCA ATTTTCGTAT CAAAAAAAAA AAAAAAAAAA TGGCGGCCGC 1275CWDVFEGLSHLQVLYLNHNYLNSLPPGVFSHLTALRGLSLNSNRLTVLSHNDLPANLEILDISRNQLLAPNPDVFVSLSVLDITHNKFICECELSTFINWLNHTNVTIAGPPADIYCVYPDSFSGVSLFSLSTEGCDEEEVLKSLKFSLFIVCTVTLTLFLMTILTVTKFRGFCFICYKTAQRLVFKDHPQGTEPDMYKYDAYLCESSKDFTWVQNALLKHLDTQYSDQNRFNLCFEERDFVPGENRIANIQDAIWNSRKIVCLVSRHFLRDGWCLEAFSYAQGRCLSDLNSALIMVVVGSLSQYQLMKHQSIRGFVQKQQYLRWPEDLQDVGWFLHKLSQQILKKEKEKKKDNNIPLQTVATIS
表6诸如灵长类动物或啮齿动物等哺乳动物的DNAX Toll样受体6(DTLR6)的核苷酸序列和氨基酸序列。SEQ ID NO11和l2来自人等灵长类动物；SEQ ID NO13和l4来自小鼠等啮齿动物。灵长类动物ATG TGG ACA CTG AAG AGA CTA ATT CTT ATC CTT TTT AAC ATA ATC CTA 48Met Trp Thr Leu Lys Arg Leu Ile Leu Ile Leu Phe Asn Ile Ile Leu-22 -20 -15 -10ATT TCC AAA CTC CTT GGG GCT AGA TGG TTT CCT AAA ACT CTG CCC TGT 96Ile Ser Lys Leu Leu Gly Ala Arg Trp Phe Pro Lys Thr Leu Pro Cys-5 1 5 10GAT GTC ACT CTG GAT GTT CCA AAG AAC CAT GTG ATC GTG GAC TGC ACA 144Asp Val Thr Leu Asp Val Pro Lys Asn His Val Ile Val Asp Cys Thr15 20 25GAC AAG CAT TTG ACA GAA ATT CCT GGA GGT ATT CCC ACG AAC ACC ACG 192Asp Lys His Leu Thr Glu Ile Pro Gly Gly Ile Pro Thr Asn Thr Thr30 35 40AAC CTC ACC CTC ACC ATT AAC CAC ATA CCA GAC ATC TCC CCA GCG TCC 240Asn Leu Thr Leu Thr Ile Asn His Ile Pro Asp Ile Ser Pro Ala Ser45 50 55TTT CAC AGA CTG GAC CAT CTG GTA GAG ATC GAT TTC AGA TGC AAC TGT 288Phe His Arg Leu Asp His Leu Val Glu Ile Asp Phe Arg Cys Asn Cys60 65 70GTA CCT ATT CCA CTG GGG TCA AAA AAC AAC ATG TGC ATC AAG AGG CTG 336Val Pro Ile Pro Leu Gly Ser Lys Asn Asn Met Cys Ile Lys Arg Leu75 80 85 90CAG ATT AAA CCC AGA AGC TTT AGT GGA CTC ACT TAT TTA AAA TCC CTT 384Gln Ile Lys Pro Arg Ser Phe Ser Gly Leu Thr Tyr Leu Lys Ser Leu95 100 105TAC CTG GAT GGA AAC CAG CTA CTA GAG ATA CCG CAG GGC CTC CCG CCT 432Tyr Leu Asp Gly Asn Gln Leu Leu Glu Ile Pro Gln Gly Leu Pro Pro110 115 120AGC TTA CAG CTT CTC AGC CTT GAG GCC AAC AAC ATC TTT TCC ATC AGA 480Ser Leu Gln Leu Leu Ser Leu Glu Ala Asn Asn Ile Phe Ser Ile Arg125 130 135AAA GAG AAT CTA ACA GAA CTG GCC AAC ATA GAA ATA CTC TAC CTG GGC 528Lys Glu Asn Leu Thr Glu Leu Ala Asn Ile Glu Ile Leu Tyr Leu Gly140 145 150CAA AAC TGT TAT TAT CGA AAT CCT TGT TAT GTT TCA TAT TCA ATA GAG 576Gln Asn Cys Tyr Tyr Arg Asn Pro Cys Tyr Val Ser Tyr Ser Ile Glu155 160 165 170
AAA GAT GCC TTC CTA AAC TTG ACA AAG TTA AAA GTG CTC TCC CTG AAA 624Lys Asp Ala Phe Leu Asn Leu Thr Lys Leu Lys Val Leu Ser Leu Lys175 180 185GAT AAC AAT GTC ACA GCC GTC CCT ACT GTT TTG CCA TCT ACT TTA ACA 672Asp Asn Asn Val Thr Ala Val Pro Thr Val Leu Pro Ser Thr Leu Thr190 195 200GAA CTA TAT CTC TAC AAC AAC ATG ATT GCA AAA ATC CAA GAA GAT GAT 720Glu Leu Tyr Leu Tyr Asn Asn Met Ile Ala Lys Ile Gln Glu Asp Asp205 210 215TTT AAT AAC CTC AAC CAA TTA CAA ATT CTT GAC CTA AGT GGA AAT TGC 768Phe Asn Asn Leu Asn Gln Leu Gln Ile Leu Asp Leu Ser Gly Asn Cys220 225 230CCT CGT TGT TAT AAT GCC CCA TTT CCT TGT GCG CCG TGT AAA AAT AAT 816Pro Arg Cys Tyr Asn Ala Pro Phe Pro Cys Ala Pro Cys Lys Asn Asn235 240 245 250TCT CCC CTA CAG ATC CCT GTA AAT GCT TTT GAT GCG CTG ACA GAA TTA 864Ser Pro Leu Gln Ile Pro Val Asn Ala Phe Asp Ala Leu Thr Glu Leu255 260 265AAA GTT TTA CGT CTA CAC AGT AAC TCT CTT CAG CAT GTG CCC CCA AGA 912Lys Val Leu Arg Leu His Ser Asn Ser Leu Gin His Val Pro Pro Arg270 275 280TGG TTT AAG AAC ATC AAC AAA CTC CAG GAA CTG GAT CTG TCC CAA AAC 960Trp Phe Lys Asn Ile Asn Lys Leu Gln Glu Leu Asp Leu Ser Gln Asn285 290 295TTC TTG GCC AAA GAA ATT GGG GAT GCT AAA TTT CTG CAT TTT CTC CCC1008Phe Leu Ala Lys Glu Ile Gly Asp Ala Lys Phe Leu His Phe Leu Pro300 305 310AGC CTC ATC CAA TTG GAT CTG TCT TTC AAT TTT GAA CTT CAG GTC TAT1056Ser Leu Ile Gln Leu Asp Leu Ser Phe Asn Phe Glu Leu Gln Val Tyr315 320 325 330CGT GCA TCT ATG AAT CTA TCA CAA GCA TTT TCT TCA CTG AAA AGC CTG1104Arg Ala Ser Met Asn Leu Ser Gln Ala Phe Ser Ser Leu Lys Ser Leu335 340 345AAA ATT CTG CGG ATC AGA GGA TAT GTC TTT AAA GAG TTG AAA AGC TTT1152Lys Ile Leu Arg Ile Arg Gly Tyr Val Phe Lys Glu Leu Lys Ser Phe350 355 360AAC CTC TCG CCA TTA CAT AAT CTT CAA AAT CTT GAA GTT CTT GAT CTT1200Asn Leu Ser Pro Leu His Asn Leu Gln Asn Leu Glu Val Leu Asp Leu365 370 375GGC ACT AAC TTT ATA AAA ATT GCT AAC CTC AGC ATG TTT AAA CAA TTT1248Gly Thr Asn Phe Ile Lys Ile Ala Asn Leu Ser Met Phe Lys Gln Phe380 385 390
AAA AGA CTG AAA GTC ATA GAT CTT TCA GTG AAT AAA ATA TCA CCT TCA 1296Lys Arg Leu Lys Val Ile Asp Leu Ser Val Asn Lys Ile Ser Pro Ser395 400 405 410GGA GAT TCA AGT GAA GTT GGC TTC TGC TCA AAT GCC AGA ACT TCT GTA 1344Gly Asp Ser Ser Glu Val Gly Phe Cys Ser Asn Ala Arg Thr Ser Val415 420 425GAA AGT TAT GAA CCC CAG GTC CTG GAA CAA TTA CAT TAT TTC AGA TAT 1392Glu Ser Tyr Glu Pro Gln Val Leu Glu Gln Leu His Tyr Phe Arg Tyr430 435 440GAT AAG TAT GCA AGG AGT TGC AGA TTC AAA AAC AAA GAG GCT TCT TTC 1440Asp Lys Tyr Ala Arg Ser Cys Arg Phe Lys Asn Lys Glu Ala Ser Phe445 450 455ATG TCT GTT AAT GAA AGC TGC TAC AAG TAT GGG CAG ACC TTG GAT CTA 1488Met Ser Val Asn Glu Ser Cys Tyr Lys Tyr Gly Gln Thr Leu Asp Leu460 465 470AGT AAA AAT AGT ATA TTT TTT GTC AAG TCC TCT GAT TTT CAG CAT CTT 1536Ser Lys Asn Ser Ile Phe Phe Val Lys Ser Ser Asp Phe Gln His Leu475 480 485 490TCT TTC CTC AAA TGC CTG AAT CTG TCA GGA AAT CTC ATT AGC CAA ACT 1584Ser Phe Leu Lys Cys Leu Asn Leu Ser Gly Asn Leu Ile Ser Gln Thr495 500 505CTT AAT GGC AGT GAA TTC CAA CCT TTA GCA GAG CTG AGA TAT TTG GAC 1632Leu Asn Gly Ser Glu Phe Gln Pro Leu Ala Glu Leu Arg Tyr Leu Asp510 515 520TTC TCC AAC AAC CGG CTT GAT TTA CTC CAT TCA ACA GCA TTT GAA GAG 1680Phe Ser Asn Asn Arg Leu Asp Leu Leu His Ser Thr Ala Phe Glu Glu525 530 535CTT CAC AAA CTG GAA GTT CTG GAT ATA AGC AGT AAT AGC CAT TAT TTT 1728Leu His Lys Leu Glu Val Leu Asp Ile Ser Ser Asn Ser His Tyr Phe540 545 550CAA TCA GAA GGA ATT ACT CAT ATG CTA AAC TTT ACC AAG AAC CTA AAG 1776Gln Ser Glu Gly Ile Thr His Mer Leu Asn Phe Thr Lys Asn Leu Lys555 560 565 570GTT CTG CAG AAA CTG ATG ATG AAC GAC AAT GAC ATC TCT TCC TCC ACC 1824Val Leu Gln Lys Leu Met Met Asn Asp Asn Asp Ile Ser Ser Ser Thr575 580 585AGC AGG ACC ATG GAG AGT GAG TCT CTT AGA ACT CTG GAA TTC AGA GGA 1872Ser Arg Thr Met Glu Ser Glu Ser Leu Arg Thr Leu Glu Phe Arg Gly590 595 600
AAT CAC TTA GAT GTT TTA TGG AGA GAA GGT GAT AAC AGA TAC TTA CAA1920Asn His Leu Asp Val Leu Trp Arg Glu Gly Asp Asn Arg Tyr Leu Gln605 610 615TTA TTC AAG AAT CTG CTA AAA TTA GAG GAA TTA GAC ATC TCT AAA AAT1968Leu Phe Lys Asn Leu Leu Lys Leu Glu Glu Leu Asp Ile Ser Lys Asn620 625 630TCC CTA AGT TTC TTG CCT TCT GGA GTT TTT GAT GGT ATG CCT CCA AAT2016Ser Leu Ser Phe Leu Pro Ser Gly Val Phe Asp Gly Met Pro Pro Asn635 640 645 650CTA AAG AAT CTC TCT TTG GCC AAA AAT GGG CTC AAA TCT TTC AGT TGG2064Leu Lys Asn Leu Ser Leu Ala Lys Asn Gly Leu Lys Ser Phe Ser Trp655 660 665AAG AAA CTC CAG TGT CTA AAG AAC CTG GAA ACT TTG GAC CTC AGC CAC2112Lys Lys Leu Gln Cys Leu Lys Asn Leu Glu Thr Leu Asp Leu Ser His670 675 680AAC CAA CTG ACC ACT GTC CCT GAG AGA TTA TCC AAC TGT TCC AGA AGC2160Asn Gln Leu Thr Thr Val Pro Glu Arg Leu Ser Asn Cys Ser Arg Ser685 690 695CTC AAG AAT CTG ATT CTT AAG AAT AAT CAA ATC AGG AGT CTG ACG AAG2208Leu Lys Asn Leu Ile Leu Lys Asn Asn Gln Ile Arg Ser Leu Thr Lys700 705 710TAT TTT CTA CAA GAT GCC TTC CAG TTG CGA TAT CTG GAT CTC AGC TCA2256Tyr Phe Leu Gln Asp Ala Phe Gln Leu Arg Tyr Leu Asp Leu Ser Ser715 720 725 730AAT AAA ATC CAG ATG ATC CAA AAG ACC AGC TTC CCA GAA AAT GTC CTC2304Asn Lys Ile Gln Met Ile Gln Lys Thr Ser Phe Pro Glu Asn Val Leu735 740 745AAC AAT CTG AAG ATG TTG CTT TTG CAT CAT AAT CGG TTT CTG TGC ACC2352Asn Asn Leu Lys Met Leu Leu Leu His His Asn Arg Phe Leu Cys Thr750 755 760TGT GAT GCT GTG TGG TTT GTC TGG TGG GTT AAC CAT ACG GAG GTG ACT2400Cys Asp Ala Val Trp Phe Val Trp Trp Val Asn His Thr Glu Val Thr765 770 775ATT CCT TAC CTG GCC ACA GAT GTG ACT TGT GTG GGG CCA GGA GCA CAC2448Ile Pro Tyr Leu Ala Thr Asp Val Thr Cys Val Gly Pro Gly Ala His780 785 790AAG GGC CAA AGT GTG ATC TCC CTG GAT CTG TAC ACC TGT GAG TTA GAT2496Lys Gly Gln Ser Val Ile Ser Leu Asp Leu Tyr Thr Cys Glu Leu Asp795 800 805 810CTG ACT AAC CTG ATT CTG TTC TCA CTT TCC ATA TCT GTA TCT CTC TTT2544Leu Thr Asn Leu Ile Leu Phe Ser Leu Ser Ile Ser Val Ser Leu Phe815 820 825
CTC ATG GTG ATG ATG ACA GCA AGT CAC CTC TAT TTC TGG GAT GTG TGG 2592Leu Met Val Met Met Thr Ala Ser His Leu Tyr Phe Trp Asp Val Trp830 835 840TAT ATT TAC CAT TTC TGT AAG GCC AAG ATA AAG GGG TAT CAG CGT CTA 2640Tyr Ile Tyr His Phe Cys Lys Ala Lys Ile Lys Gly Tyr Gln Arg Leu845 850 855ATA TCA CCA GAC TGT TGC TAT GAT GCT TTT ATT GTG TAT GAC ACT AAA 2688Ile Ser Pro Asp Cys Cys Tyr Asp Ala Phe Ile Val Tyr Asp Thr Lys860 865 870GAC CCA GCT GTG ACC GAG TGG GTT TTG GCT GAG CTG GTG GCC AAA CTG 2736Asp Pro Ala Val Thr Glu Trp Val Leu Ala Glu Leu Val Ala Lys Leu875 880 885 890GAA GAC CCA AGA GAG AAA CAT TTT AAT TTA TGT CTC GAG GAA AGG GAC 2784Glu Asp Pro Arg Glu Lys His Phe ASn Leu Cys Leu Glu Glu Arg Asp895 900 905TGG TTA CCA GGG CAG CCA GTT CTG GAA AAC CTT TCC CAG AGC ATA CAG 2832Trp Leu Pro Gly Gln Pro Val Leu Glu Asn Leu Ger Gln Ser Ile Gln910 915 920CTT AGC AAA AAG ACA GTG TTT GTG ATG ACA GAC AAG TAT GCA AAG ACT 2880Leu Ser Lys Lys Thr Val Phe Val Met Thr Asp Lys Tyr Ala Lys Thr925 930 935GAA AAT TTT AAG ATA GCA TTT TAC TTG TCC CAT CAG AGG CTC ATG GAT 2928Glu Asn Phe Lys Ile Ala Phe Tyr Leu Ser His Gln Arg Leu Met Asp940 945 950GAA AAA GTT GAT GTG ATT ATC TTG ATA TTT CTT GAG AAG CCC TTT CAG 2976Glu Lys Val Asp Val Ile Ile Leu Ile Phe Leu Glu Lys Pro Phe Gln955 960 965 970AAG TCC AAG TTC CTC CAG CTC CGG AAA AGG CTC TGT GGG AGT TCT GTC 3024Lys Ser Lys Phe Leu Gln Leu Arg Lys Arg Leu Cys Gly Ser Ser Val975 980 985CTT GAG TGG CCA ACA AAC CCG CAA GCT CAC CCA TAC TTC TGG CAG TGT 3072Leu Glu Trp Pro Thr Asn Pro Gln Ala His Pro Tyr Phe Trp Gln Cys990 995 1000CTA AAG AAC GCC CTG GCC ACA GAC AAT CAT GTG GCC TAT AGT CAG GTG 3120Leu Lys Asn Ala Leu Ala Thr Asp Asn His Val Ala Tyr Ser Gln Val100510101015TTC AAG GAA ACG GTC TAG 3138Phe Lys Glu Thr Val1020MWTLKRLILILFNIILISKLLGARWFPKTLPCDVTLDVPKNHVIVDCTDKHLTEIPGGIPTNTTNLTLTINHIPDISPASFHRLDHLVEIDFRCNCVPIPLGSKNNMCIKRLQIKPRSFSGLTYLKSLYLDGNQLLEIPQGLPPSLQL
LSLEANNIFSIRKENLTELANIEILYLGQNCYYRNPCYVSYSIEKDAFLNLTKLKVLSLKDNNVTAVPTVLPSTLTELYLYNNMIAKIQEDDFNNLNQLQILDLSGNCPRCYNAPFPCAPCKNNSPLQIPVNAFDALTELKVLRLHSNSLQHVPPRWFKNINKLQELDLSQNFLAKEIGDAKFLHFLPSLIQLDLSFNFELQVYRASMNLSQAFSSLKSLKILRIRGYVFKELKSFNLSPLHNLQNLEVLDLGTNFIKIANLSMFKQFKRLKVIDLSVNKISPSGDSSEVGFCSNARTSVESYEPQVLEQLHYFRYDKYARSCRFKNKEASFMSVNESCYKYGQTLDLSKNSIFFVKSSDFQHLSFLKCLNLSGNLISQTLNGSEFQPLAELRYLDFSNNRLDLLHSTAFEELHKLEVLDISSNSHYFQSEGITHMLNFTKNLKVLQKLMMNDNDISSSTSRTMESESLRTLEFRGNHLDVLWREGDNRYLQLFKNLLKLEELDISKNSLSFLPSGVFDGMPPNLKNLSLAKNGLKSFSWKKLQCLKNLETLDLSHNQLTTVPERLSNCSRSLKNLILKNNQIRSLTKYFLQDAFQLRYLDLSSNKIQMIQKTSFPENVLNNLKMLLLHHNRFLCTCDAVWFVWWVNHTEVTIPYLATDVTCVGPGAHKGQSVISLDLYTCELDLTNLILFSLSISVSLFLMVMMTASHLYFWDVWYIYHFCKAKIKGYQRLISPDCCYDAFIVYDTKDPAVTEWVLAELVAKLEDPREKHFNLCLEERDWLPGQPVLENLSQSIQLSKKTVFVMTDKYAKTENFKIAFYLSHQRLMDEKVDVIILIFLEKPFQKSKFLQLRKRLCGSSVLEWPTNPQAHPYFWQCLKNALATDNHVAYSQVFKETV
啮齿动物(SEQ ID NO13和14)CTT GGA AAA CCT CTT CAG AAG TCT AAG TTT CTT CAG CTC AGG AAG AGA 48Leu Gly Lys Pro Leu Gln Lys Ser Lys Phe Leu Gln Leu Arg Lys Arg1 5 10 15CTC TGC AGG AGC TCT GTC CTT GAG TGG CCT GCA AAT CCA CAG GCT CAC 96Leu Cys Arg Ser Ser Val Leu Glu Trp Pro Ala Asn Pro Gln Ala His20 25 30CCA TAC TTC TGG CAG TGC CTG AAA AAT GCC CTG ACC ACA GAC AAT CAT 144Pro Tyr Phe Trp Gln Cys Leu Lys Asn Ala Leu Thr Thr Asp Asn His35 40 45GTG GCT TAT AGT CAA ATG TTC AAG GAA ACA GTC TAG 180Val Ala Tyr Ser Gln Met Phe Lys Glu Thr Val50 55LGGKPLQKSKFLQLRKRLCRSSVLEWPANPQAHPYFWQCLKALTTDNHVAYSQMFKETV诸如小鼠等啮齿动物的附加序列上游(SEQ ID NO27和28)；用C表示的第186、196、217、276和300位核苷酸的每个都可以是A、C、G或TTCC TAT TCT ATG GAA AAA GAT GCT TTC CTA TTT ATG AGA AAT TTG AAG 48Ser Tyr Ser Met Glu Lys Asp Ala Phe Leu Phe Met Arg Asn Leu Lys1 5 10 15GTT CTC TCA CTA AAA GAT AAC AAT GTC ACA GCT GTC CCC ACC ACT TTG 96Val Leu Ser Leu Lys Asp Asn Asn Val Thr Ala Val Pro Thr Thr Leu20 25 30CCA CCT AAT TTA CTA GAG CTC TAT CTT TAT AAC AAT ATC ATT AAG AAA 144Pro Pro Asn Leu Leu Glu Leu Tyr Leu Tyr Asn Asn Ile Ile Lys Lys35 40 45ATC CAA GAA AAT GAT TTC AAT AAC CTC AAT GAG TTG CAA GTC CTT GAC 192Ile Gln Glu Asn Asp Phe Asn Asn Leu Asn Glu Leu Gln Val Leu Asp50 55 60CTA CGT GGA AAT TGC CCT CGA TGT CAT AAT GTC CCA TAT CCG TGT ACA 240Leu Arg Gly Asn Cys Pro Arg Cys His Asn Val Pro Tyr Pro Cys Thr65 70 75 80CCG TGT GAA AAT AAT TCC CCC TTA CAG ATC CAT GAC AAT GCT TTC AAT 288Pro Cys Glu Asn Asn Ser Pro Leu Gln Ile His Asp Asn Ala Phe Asn85 90 95TCA TCG ACA GAC 300Ser Ser Thr Asp100
SYSMEKDAFLFMRNLKVLSLKDNNVTAVPTTLPPNLLELYLYNNIIKKIQENDFNNLNELQXLDLXGNCPRCXNVPYPCTPCENNSPLQIHXNAFNSSTX下游(SEQ ID NO29和30)；用A表示的第1643位核苷酸可以是A或G；用C表示的第1664位核苷酸可以是A、C、G或T；用G表示的第1680和1735位核苷酸可以是G或T；用C表示的第1719位核苷酸可以是C或T；并且用A表示的第1727位核苷酸可以是A、G或TTCT CCA GAA ATT CCC TGG AAT TCC TTG CCT CCT GAG GTT TTT GAG GGT 48Ser Pro Glu Ile Pro Trp Asn Ser Leu Pro Pro Glu Val Phe Glu Gly1 5 10 15ATG CCG CCA AAT CTA AAG AAT CTC TCC TTG GCC AAA AAT GGG CTC AAA 96Met Pro Pro Asn Leu Lys Asn Leu Ser Leu Ala Lys Asn Gly Leu Lys20 25 30TCT TTC TTT TGG GAC AGA CTC CAG TTA CTG AAG CAT TTG GAA ATT TTG144Ser Phe Phe Trp Asp Arg Leu Gln Leu Leu Lys His Leu Glu Ile Leu35 40 45GAC CTC AGC CAT AAC CAG CTG ACA AAA GTA CCT GAG AGA TTG GCC AAC192Asp Leu Ser His Asn Gln Leu Thr Lys Val Pro Glu Arg Leu Ala Asn50 55 60TGT TCC AAA AGT CTC ACA ACA CTG ATT CTT AAG CAT AAT CAA ATC AGG240Cys Ser Lys Ser Leu Thr Thr Leu Ile Leu Lys His Asn Gln Ile Arg65 70 75 80CAA TTG ACA AAA TAT TTT CTA GAA GAT GCT TTG CAA TTG CGC TAT CTA288Gln Leu Thr Lys Tyr Phe Leu Glu Asp Ala Leu Gln Leu Arg Tyr Leu85 90 95GAC ATC AGT TCA AAT AAA ATC CAG GTC ATT CAG AAG ACT AGC TTC CCA336Asp Ile Ser Ser Asn Lys Ile Gln Val Ile Gln Lys Thr Ser Phe Pro100 105 110GAA AAT GTC CTC AAC AAT CTG GAG ATG TTG GTT TTA CAT CAC AAT CGC384Glu Asn Val Leu Asn Asn Leu Glu Met Leu Val Leu His His Asn Arg115 120 125TTT CTT TGC AAC TGT GAT GCT GTG TGG TTT GTC TGG TGG GTT AAC CAT432Phe Leu Cys Asn Cys Asp Ala Val Trp Phe Val Trp Trp Val Asn His130 135 140ACA GAT GTT ACT ATT CCA TAC CTG GCC ACT GAT GTG ACT TGT GTA GGT480Thr Asp Val Thr Ile Pro Tyr Leu Ala Thr Asp Val Thr Cys Val Gly145 150 155 160CCA GGA GCA CAC AAA GGT CAA AGT GTC ATA TCC CTT GAT CTG TAT ACG528Pro Gly Ala His Lys Gly Gln Ser Val Ile Ser Leu Asp Leu Tyr Thr165 170 175
TGT GAG TTA GAT CTC ACA AAC CTG ATT CTG TTC TCA GTT TCC ATA TCA576Cys Glu Leu Asp Leu Thr Asn Leu Ile Leu Phe Ser Val Ser Ile Ser180 185 190TCA GTC CTC TTT CTT ATG GTA GTT ATG ACA ACA AGT CAC CTC TTT TTC624Ser Val Leu Phe Leu Met Val Val Met Thr Thr Ser His Leu Phe Phe195 200 205TGG GAT ATG TGG TAC ATT TAT TAT TTT TGG AAA GCA AAG ATA AAG GGG672Trp Asp Met Trp Tyr Ile Tyr Tyr Phe Trp Lys Ala Lys Ile Lys Gly210 215 220TAT CCA GCA TCT GCA ATC CCA TGG AGT CCT TGT TAT GAT GCT TTT ATT720Tyr Pro Ala Ser Ala Ile Pro Trp Ser Pro Cys Tyr Asp Ala Phe Ile225 230 235 240GTG TAT GAC ACT AAA AAC TCA GCT GTG ACA GAA TGG GTT TTG CAG GAG768Val Tyr Asp Thr Lys Asn Ser Ala Val Thr Glu Trp Val Leu Gln Glu245 250 255CTG GTG GCA AAA TTG GAA GAT CCA AGA GAA AAA CAC TTC AAT TTG TGT816Leu Val Ala Lys Leu Glu Asp Pro Arg Glu Lys His Phe Asn Leu Cys260 265 270CTA GAA GAA AGA GAC TGG CTA CCA GGA CAG CCA GTT CTA GAA AAC CTT864Leu Glu Glu Arg Asp Trp Leu Pro Gly Gln Pro Val Leu Glu Asn Leu275 280 285TCC CAG AGC ATA CAG CTC AGC AAA AAG ACA GTG TTT GTG ATG ACA CAG912Ser Gln Ser Ile Gln Leu Ser Lys Lys Thr Val Phe val Met Thr Gln290 295 300AAA TAT GCT AAG ACT GAG AGT TTT AAG ATG GCA TTT TAT TTG TCT CAT960Lys Tyr Ala Lys Thr Glu Ser Phe Lys Met Ala Phe Tyr Leu Ser His305 310 315 320CAG AGG CTC CTG GAT GAA AAA GTG GAT GTG ATT ATC TTG ATA TTC TTG 1008Gln Arg Leu Leu Asp Glu Lys Val Asp Val Ile Ile Leu Ile Phe Leu325 330 335GAA AGA CCT CTT CAG AAG TCT AAG TTT CTT CAG CTC AGG AAG AGA CTC 1056Glu Arg Pro Leu Gln Lys Ser Lys Phe Leu Gln Leu Arg Lys Arg Leu340 345 350TGC AGG AGC TCT GTC CTT GAG TGG CCT GCA AAT CCA CAG GCT CAC CCA 1104Cys Arg Ser Ser Val Leu Glu Trp Pro Ala Asn Pro Gln Ala His Pro355 360 365TAC TTC TGG CAG TGC CTG AAA AAT GCC CTG ACC ACA GAC AAT CAT GTG 1152Tyr Phe Trp Gln Cys Leu Lys Asn Ala Leu Thr Thr Asp Asn His Val370 375 380GCT TAT AGT CAA ATG TTC AAG GAA ACA GTC TAGCTCTCTG AAGAATGTCA 1202Ala Tyr Ser Gln Mer Phe Lys Glu Thr Val385 390
CCACCTAGGA CATGCCTTGG TACCTGAAGT TTTCATAAAG GTTTCCATAA ATGAAGGTCT1262GAATTTTTCC TAACAGTTGT CATGGCTCAG ATTGGTGGGA AATCATCAAT ATATGGCTAA1322GAAATTAAGA AGGGGAGACT GATAGAAGAT AATTTCTTTC TTCATGTGCC ATGCTCAGTT1382AAATATTTCC CCTAGCTCAA ATCTGAAAAA CTGTGCCTAG GAGACAACAC AAGGCTTTGA1442TTTATCTGCA TACAATTGAT AAGAGCCACA CATCTGCCCT GAAGAAGTAC TAGTAGTTTT1502AGTAGTAGGG TAAAAATTAC ACAAGCTTTC TCTCTCTCTG ATACTGAACT GTACCAGAGT1562TCAATGAAAT AAAAGCCCAG AGAACTTCTC AGTAAATGGT TTCATTATCA TGTAGTATCC1622ACCATGCAAT ATGCCACAAA ACCGCTACTG GTACAGGACA GCTGGTAGCT GCTTCAAGGC1682CTCTTATCAT TTTCTTGGGG CCCATGGAGG GGTTCTCTGG GAAAAAGGGA AGGTTTTTTT1742TGGCCATCCA TGAA 1756SPEIPWNSLPPEVFEGMPPNLKNLSLAKNGLKSFFWDRLQLLKHLEILDLSHNQLTKVPERLANCSKSLTTLILKHNQIRQLTKYFLEDALQLRYLDISSNKIQVIQKTSFPENVLNNLEMLVLHHNRFLCNCDAVWFVWWVNHTDVTIPYLATDVTCVGPGAHKGQSVISLDLYTCELDLTNLILFSVSISSVLFLMVVMTTSHLFFWDMWYIYYFWKAKIKGYPASAIPWSPCYDAFIVYDTKNSAVTEWVLQELVAKLEDPREKHFNLCLEERDWLPGQPVLENLSQSIQLSKKTVFVMTQKYAKTESFKMAFYLSHQRLLDEKVDVIILIFLERPLQKSKFLQLRKRLCRSSVLEWPANPQAHPYFWQCLKNALTTDNHVAYSQMFKETV
表7诸如灵长类动物或人等哺乳动物的DNAX Toll样受体7(DTLR7)的核苷酸序列和氨基酸序列。
上游(SEQ ID NO15和16)G AAT TCC AGA CTT ATA AAC TTG AAA AAT CTC TAT TTG GCC TGG AAC 46Asn Ser Arg Leu Ile Asn Leu Lys Asn Leu Tyr Leu Ala Trp Asn1 5 10 15TGC TAT TTT AAC AAA GTT TGC GAG AAA ACT AAC ATA GAA GAT GGA GTA 94Cys Tyr Phe Asn Lys Val Cys Glu Lys Thr Asn Ile Glu Asp Gly Val20 25 30TTT GAA ACG CTG ACA AAT TTG GAG TTG CTA TCA CTA TCT TTC AAT TCT142Phe Glu Thr Leu Thr Asn Leu Glu Leu Leu Ser Leu Ser Phe Asn Ser35 40 45CTT TCA CAT GTG CCA CCC AAA CTG CCA AGC TCC CTA CGC AAA CTT TTT190Leu Ser His Val Pro Pro Lys Leu Pro Ser Ser Leu Arg Lys Leu Phe50 55 60CTG AGC AAC ACC CAG ATC AAA TAC ATT AGT GAA GAA GAT TTC AAG GGA238Leu Ser Asn Thr Gln Ile Lys Tyr Ile Ser Glu Glu Asp Phe Lys Gly65 70 75TTG ATA AAT TTA ACA TTA CTA GAT TTA AGC GGG AAC TGT CCG AGG TGC286Leu Ile Asn Leu Thr Leu Leu Asp Leu Ser Gly Asn Cys Pro Arg Cys80 85 90 95TTC AAT GCC CCA TTT CCA TGC GTG CCT TGT GAT GGT GGT GCT TCA ATT334Phe Asn Ala Pro Phe Pro Cys Val Pro Cys Asp Gly Gly Ala Ser Ile100 105 110AAT ATA GAT CGT TTT GCT TTT CAA AAC TTG ACC CAA CTT CGA TAC CTA382Asn Ile Asp Arg Phe Ala Phe Gln Asn Leu Thr Gln Leu Arg Tyr Leu115 120 125AAC CTC TCT AGC ACT TCC CTC AGG AAG ATT AAT GCT GCC TGG TTT AAA430Asn Leu Ser Ser Thr Ser Leu Arg Lys Ile Asn Ala Ala Trp Phe Lys130 135 140AAT ATG CCT CAT CTG AAG GTG CTG GAT CTT GAA TTC AAC TAT TTA GTG478Asn Met Pro His Leu Lys Val Leu Asp Leu Glu Phe Asn Tyr Leu Val145 150 155GGA GAA ATA GCC TCT GGG GCA TTT TTA ACG ATG CTG CCC CGC TTA GAA526Gly Glu Ile Ala Ser Gly Ala Phe Leu Thr Met Leu Pro Arg Leu Glu160 165 170 175ATA CTT GAC TTG TCT TTT AAC TAT ATA AAG GGG AGT TAT CCA CAG CAT574Ile Leu Asp Leu Ser Phe Asn Tyr Ile Lys Gly Ser Tyr Pro Gln His180 185 190
ATT AAT ATT TCC AGA AAC TTC TCT AAA CTT TTG TCT CTA CGG GCA TTG622I1e Asn Ile Ser Arg Asn Phe Ser Lys Leu Leu Ser Leu Arg Ala Leu195 200 205CAT TTA AGA GGT TAT GTG TTC CAG GAA CTC AGA GAA GAT GAT TTC CAG670His Leu Arg Gly Tyr Val Phe Gln Glu Leu Arg Glu Asp Asp Phe Gln210 215 220CCC CTG ATG CAG CTT CCA AAC TTA TCG ACT ATC AAC TTG GGT ATT AAT718Pro Leu Met Gln Leu Pro Asn Leu Ser Thr Ile Asn Leu Gly Ile Asn225 230 235TTT ATT AAG CAA ATC GAT TTC AAA CTT TTC CAA AAT TTC TCC AAT CEG766Phe Ile Lys Gln Ile Asp Phe Lys Leu Phe Gln Asn Phe Ser Asn Leu240 245 250 255GAA ATT ATT TAC TTG TCA GAA AAC AGA ATA TCA CCG TTG GTA AAA GAT814Glu Ile Ile Tyr Leu Ser Glu Asn Arg Ile Ser Pro Leu Val Lys Asp260 265 270ACC CGG CAG AGT TAT GCA AAT AGT TCC TCT TTT CAA CGT CAT ATC CGG862Thr Arg Gln Ser Tyr Ala Asn Ser Ser Ser Phe Gln Arg His Ile Arg275 280 285AAA CGA CGC TCA ACA GAT TTT GAG TTT GAC CCA CAT TCG AAC TTT TAT910Lys Arg Arg Ser Thr Asp Phe Glu Phe Asp Pro His Ser Asn Phe Tyr290 295 300CAT TTC ACC CGT CCT TTA ATA AAG CCA CAA TGT GCT GCT TAT GGA AAA958His Phe Thr Arg Pro Leu Ile Lys Pro Gln Cys Ala Ala Tyr Gly Lys305 310 315GCC TTA GAT TTA AGC CTC AAC AGT ATT TTC TT 990Ala Leu Asp Leu Ser Leu Asn Ser Ile Phe320 325NSRLINLKNLYLAWNCYFNKVCEKTNIEDGVFETLTNLELLSLSFNSLSHVPPKLPSSLRKLFLSNTQIKYISEEDFKGLINLTLLDLSGNCPRCFNAPFPCVPCDGGASINIDRFAFQNLTQLRYLNLSSTSLRKINAAWFKNMPHLKVLDLEFNYLVGEIASGAFLTMLPRLEILDLSFNYIKGSYPQHINISRNFSKLLSLRALHLRGYVFQELREDDFQPLMQLPNLSTINLGINFIKQIDFKLFQNFSNLEIIYLSENRISPLVKDTRQSYANSSSFQRHIRKRRSTDFEFDPHSNFYHFTRPLIKPQCAAYGKALDLSLNSIF下游(SEQ ID NO17和18)CAG TCT CTT TCC ACA TCC CAA ACT TTC TAT GAT GCT TAC ATT TCT TAT 48Gln Ser Leu Ser Thr Ser Gln Thr Phe Tyr Asp Ala Tyr Ile Ser Tyr1 5 10 15GAC ACC AAA GAT GCC TCT GTT ACT GAC TGG GTG ATA AAT GAG CTG CGC 96Asp Thr Lys Asp Ala Ser Val Thr Asp Trp Val Ile Asn Glu Leu Arg20 25 30
TAC CAC CTT GAA GAG AGC CGA GAC AAA AAC GTT CTC CTT TGT CTA GAG 144Tyr His Leu Glu Glu Ser Arg Asp Lys Asn Val Leu Leu Cys Leu Glu35 40 45GAG AGG GAT TGG GAC CCG GGA TTG GCC ATC ATC GAC AAC CTC ATG CAG 192Glu Arg Asp Trp Asp Pro Gly Leu Ala Ile Ile Asp Asn Leu Met Gln50 55 60AGC ATC AAC CAA AGC AAG AAA ACA GTA TTT GTT TTA ACC AAA AAA TAT 240Ser Ile Asn Gln Ser Lys Lys Thr Val Phe Val Leu Thr Lys Lys Tyr65 70 75 80GCA AAA AGC TGG AAC TTT AAA ACA GCT TTT TAC TTG GGC TTG CAG AGG 288Ala Lys Ser Trp Asn Phe Lys Thr Ala Phe Tyr Leu Gly Leu Gln Arg85 90 95CTA ATG GGT GAG AAC ATG GAT GTG ATT ATA TTT ATC CTG CTG GAG CCA 336Leu Met Gly Glu Asn Met Asp Val Ile Ile Phe Ile Leu Leu Glu Pro100 105 110GTG TTA CAG CAT TCT CCG TAT TTG AGG CTA CGG CAG CGG ATC TGT AAG 384Val Leu Gln His Ser Pro Tyr Leu Arg Leu Arg Gln Arg Ile Cys Lys115 120 125AGC TCC ATC CTC CAG TGG CCT GAC AAC CCG AAG GCA GAA AGG TTG TTT 432Ser Ser Ile Leu Gln Trp Pro Asp Asn Pro Lys Ala Glu Arg Leu Phe130 135 140TGG CAA ACT CTG AGA AAT GTG GTC TTG ACT GAA AAT GAT TCA CGG TAT 480Trp Gln Thr Leu Arg Asn Val Val Leu Thr Glu Asn Asp Ser Arg Tyr145 150 155 160AAC AAT ATG TAT GTC GAT TCC ATT AAG CAA TAC TAACTGACGT TAAGTCATGA 533Asn Asn Met Tyr Val Asp Ser Ile Lys Gln Tyr165 170TTTCGCGCCA TAATAAAGAT GCAAAGGAAT GACATTTCCG TATTAGTTAT CTATTGCTAC 593GGTAACCAAA TTACTCCCAA AAACCTTACG TCGGTTTCAA AACAACCACA TTCTGCTGGC 653CCCACAGTTT TTGAGGGTCA GGAGTCCAGG CCCAGCATAA CTGGGTCTTC TGCTTCAGGG 713TGTCTCCAGA GGCTGCAATG TAGGTGTTCA CCAGAGACAT AGGCATCACT GGGGTCACAC 773TCCATGTGGT TGTTTTCTGG ATTCAATTCC TCCTGGGCTA TTGGCCAAAG GCTATACTCA 833TGTAAGCCAT GCGAGCCTAT CCCACAACGG CAGCTTGCTT CATCAGAGCT AGCAAAAAAG 893AGAGGTTGCT AGCAAGATGA AGTCACAATC TTTTGTAATC GAATCAAAAA AGTGATATCT 953CATCACTTTG GCCATATTCT ATTTGTTAGA AGTAAACCAC AGGTCCCACC AGCTCCATGG1013GAGTGACCAC CTCAGTCCAG GGAAAACAGC TGAAGACCAA GATGGTGAGC TCTGATTGCT1073TCAGTTGGTC ATCAACTATT TTCCCTTGAC TGCTGTCCTG GGATGGCCGG CTATCTTGAT1133
GGATAGATTG TGAATATCAG GAGGCCAGGG ATCACTGTGG ACCATCTTAG CAGTTGACCT1193AACACATCTT CTTTTCAATA TCTAAGAACT TTTGCCACTG TGACTAATGG TCCTAATATT1253AAGCTGTTGT TTATATTTAT CATATATCTA TGGCTACATG GTTATATTAT GCTGTGGTTG1313CGTTCGGTTT TATTTACAGT TGCTTTTACA AATATTTGCT GTAACATTTG ACTTCTAAGG1373TTTAGATGCC ATTTAAGAAC TGAGATGGAT AGCTTTTAAA GCATCTTTTA CTTCTTACCA1433TTTTTTAAAA GTATGCAGCT AAATTCGAAG CTTTTGGTCT ATATTGTTAA TTGCCATTGC1493TGTAAATCTT AAAATGAATG AATAAAAATG TTTCATTTTA AAAAAAAAAA AAAAAAAAAA1553AAAA 1557QSLSTSQTFYDAYISYDTKDASVTDWVINELRYHLEESRDKNVLLCLEERDWDPGLAIIDNLMQSINQSKKTVFVLTKKYAKSWNFKTAFYLGLQRLMGENMDVIIFILLEPVLQHSPYLRLRQRICKSSILQWPDNPKAERLFWQTLRNVVLTENDSRYNNMYVDSIKQY诸如人等灵长类动物的DTLR7的其他序列(SEQ ID NO37和37)。
atg ctg acc tgc att ttc ctg cta ata tct ggt tcc tgt gag tta tgc 48Met Leu Thr Cys Ile Phe Leu Leu Ile Ser Gly Ser Cys Glu Leu Cys-15 -10 -5gcc gaa gaa aat ttt tct aga agc tat cct tgt gat gag aaa aag caa 96Ala Glu Glu Asn Phe Ser Arg Ser Tyr Pro Cys Asp Glu Lys Lys Gln-1 1 5 10 15aat gac rca gtt att gca gag tgc agc aat cgt cga cta cag gaa gtt 144Asn Asp Ser Val Ile Ala Glu Cys Ser Asn Arg Arg Leu Gln Glu Val20 25 30ccc caa acg gtg ggc aaa tat gtg aca gaa cta gac ctg tct gat aat 192Pro Gln Thr Val Gly Lys Tyr Val Thr Glu Leu Asp Leu Set Asp Asn35 40 45ttc atc aca cac ata acg aat gaa tca ttt caa ggg ctg caa aat ctc 240Phe Ile Thr His Ile Thr Asn Glu Ser Phe Gln Gly Leu Gln Asn Leu50 55 60act aaa ata aat cta aac cac aac ccc aat gta cag cac cag aac gga 288Thr Lys Ile Asn Leu Asn His Asn Pro Asn Val Gln His Gln Asn Gly65 70 75aat ccc ggt ata caa tca aat ggc ttg aat atc aca gac ggg gca ttc 336Asn Pro Gly Ile Gln Set Asn Gly Leu Asn Ile Thr Asp Gly Ala Phe80 85 90 95ctc aac cta aaa aac cta agg gag tta ctg ctt gaa gac aac cag tta 384Leu Asn Leu Lys Asn Leu Arg Glu Leu Leu Leu Glu Asp Asn Gln Leu100 105 110
ccc caa ata ccc tct ggt ttg cca gag tct ttg aca gaa ctt agt cta 432Pro Gln Ile Pro Ser Gly Leu Pro Glu Ser Leu Thr Glu Leu Ser Leu115 120 125att caa aac aat ata tac aac ata act aaa gag ggc att tca aga ctt 480Ile Gln Asn Asn Ile Tyr Asn Ile Thr Lys Glu Gly Ile Ser Arg Leu130 135 140ata aac ttg aaa aat ctc tat ttg gcc tgg aac tgc tat ttt aac aaa 528Ile Asn Leu Lys Asn Leu Tyr Leu Ala Trp Asn Cys Tyr Phe Asn Lys145 150 155gtt tgc gag aaa act aac ata gaa gat gga gta ttt gaa acg ctg aca 576Val Cys Glu Lys Thr Asn Ile Glu Asp Gly Val Phe Glu Thr Leu Thr160 165 170 175aat ttg gag ttg cta tca cta tct ttc aat tct ctt tca cat gtg cca 624Asn Leu Glu Leu Leu Ser Leu Ser Phe Asn Ser Leu Ser His Val Pro180 185 190ccc aaa ctg cca agc tcc cta cgc aaa ctt ttt ctg agc aac acc cag 672Pro Lys Leu Pro Ser Set Leu Arg Lys Leu Phe Leu Set Asn Thr Gln195 200 205atc aaa tac att agt gaa gaa gat ttc aag gga ttg ata aat tta aca 720Ile Lys Tyr Ile Ser Glu Glu Asp Phe Lys Gly Leu Ile Asn Leu Thr210 215 220tta cta gat tta agc ggg aac tgt ccg agg tgc ttc aat gcc cca ttt 768Leu Leu Asp Leu Ser Gly Asn Cys Pro Arg Cys Phe Asn Ala Pro Phe225 230 235cca tgc gtg cct tgt gat ggt ggt gct tca att aat ata gat cgt ttt 816Pro Cys Val Pro Cys Asp Gly Gly Ala Ser Ile Asn Ile Asp Arg Phe240 245 250 255gct ttt caa aac ttg acc caa ctt cga tac cta aac ctc tct agc act 864Ala Phe Gln Asn Leu Thr Gln Leu Arg Tyr Leu Asn Leu Ser Ser Thr260 265 270tcc ctc agg aag att aat gct gcc tgg ttt aaa aat atg cct cat ctg 912Ser Leu Arg Lys Ile Asn Ala Ala Trp Phe Lys Asn Met Pro His Leu275 280 285aag gtg ctg gat ctt gaa ttc aac tat tta gtg gga gaa ata gcc tct 960Lys Val Leu Asp Leu Glu Phe Asn Tyr Leu Val Gly Glu Ile Ala Ser290 295 300ggg gca ttt tta acg atg ctg ccc cgc tta gaa ata ctt gac ttg tct 1008Gly Ala Phe Leu Thr Met Leu Pro Arg Leu Glu Ile Leu Asp Leu Ser305 310 315ttt aac tat ata aag ggg agt tat cca cag cat att aat att tcc aga 1056Phe Asn Tyr Ile Lys Gly Ser Tyr Pro Gln His Ile Asn Ile Ser Arg320 325 330 335
aac ttc tct aaa ctt ttg tct cta cgg gca ttg cat tta aga ggt tat1104Asn Phe Ser Lys Leu Leu Ser Leu Arg Ala Leu His Leu Arg Gly Tyr340 345 350gtg ttc cag gaa ctc aga gaa gat gat ttc cag ccc ctg atg cag ctt1152Val Phe Gln Glu Leu Arg Glu Asp Asp Phe Gln Pro Leu Met Gln Leu355 360 365cca aac tta tcg act atc aac ttg ggt att aat ttt att aag caa atc1200Pro Asn Leu Ser Thr Ile Asn Leu Gly Ile Asn Phe Ile Lys Gln Ile370 375 380gat ttc aaa ctt ttc caa aat ttc tcc aat ctg gaa att att tac ttg1248Asp Phe Lys Leu Phe Gln Asn Phe Ser Asn Leu Glu Ile Ile Tyr Leu385 390 395tca gaa aac aga ata tca ccg ttg gta aaa gat acc cgg cag agt tat1296Ser Glu Asn Arg Ile Ser Pro Leu Val Lys Asp Thr Arg Gln Ser Tyr400 405 410 415gca aat agt tcc tct ttt caa cgt cat atc cgg aaa cga cgc tca aca1344Ala Asn Ser Ser Ser Phe Gln Arg His Ile Arg Lys Arg Arg Ser Thr420 425 430gat ttt gag ttt gac cca cat tcg aac ttt tat cat ttc acc cgt cct1392Asp Phe Glu Phe Asp Pro His Ser Asn Phe Tyr His Phe Thr Arg Pro435 440 445tta ata aag cca caa tgt gct gct tat gga aaa gcc tta gat tta agc1440Leu Ile Lys Pro Gln Cys Ala Ala Tyr Gly Lys Ala Leu Asp Leu Ser450 455 460ctc aac agt att ttc ttc att ggg cca aac caa ttt gaa aat ctt cct1488Leu Asn Ser Ile Phe Phe Ile Gly Pro Asn Gln Phe Glu Asn Leu Pro465 470 475gac att gcc tgt tta aat ctg tct gca aat agc aat gct caa gtg tta1536Asp Ile Ala Cys Leu Asn Leu Ser Ala Asn Ser Asn Ala Gln Val Leu480 485 490 495agt gga act gaa ttt tca gcc att cct cat gtc aaa tat ttg gat ttg1584Ser Gly Thr Glu Phe Ser Ala Ile Pro His Val Lys Tyr Leu Asp Leu500 505 510aca aac aat aga cta gac ttt gat aat gct agt gct ctt act gaa ttg1632Thr Asn Asn Arg Leu Asp Phe Asp Asn Ala Ser Ala Leu Thr Glu Leu515 520 525tcc gac ttg gaa gtt cta gat ctc agc tat aat tca cac tat ttc aga1680Ser Asp Leu Glu Val Leu Asp Leu Ser Tyr Asn Ser His Tyr Phe Arg530 535 540ata gca ggc gta aca cat cat cta gaa ttt att caa aat ttc aca aat1728Ile Ala Gly Val Thr His His Leu Glu Phe Ile Gln Asn Phe Thr Asn545 550 555cta aaa gtt tta aac ttg agc cac aac aac att tat act tta aca gat1776Leu Lys Val Leu Asn Leu Ser His Asn Asn Ile Tyr Thr Leu Thr Asp
560 565 570 575aag tat aac ctg gaa agc aag tcc ctg gta gaa tta gtt ttc agt ggc 1824Lys Tyr Asn Leu Glu Ser Lys Ser Leu Val Glu Leu Val Phe Ser Gly580 585 590aat cgc ctt gac att ttg tgg aat gat gat gac aac agg tat atc tcc 1872Asn Arg Leu Asp Ile Leu Trp Asn Asp Asp Asp Asn Arg Tyr Ile Ser595 600 605
att ttc aaa ggt ctc aag aat ctg aca cgt ctg gat tta tcc ctt aat 1920Ile Phe Lys Gly Leu Lys Asn Leu Thr Arg Leu Asp Leu Ser Leu Asn610 615 620agg ctc aag cac atc cca aat gaa gca ttc ctt aat ttg cca gcg agt 1968Arg Leu Lys His Ile Pro Asn Glu Ala Phe Leu Asn Leu Pro Ala Ser625 630 635ctc act gaa cta cat ata aat gat aat atg tta aag ttt ttt aac tgg 2016Leu Thr Glu Leu His Ile Asn Asp Asn Met Leu Lys Phe Phe Asn Trp640 645 650 655aca tta ctc cag cag ttt cct cgt ctc gag ttg ctt gac tta cgt gga 2064Thr Leu Leu Gln Gln Phe Pro Arg Leu Glu Leu Leu Asp Leu Arg Gly660 665 670aac aaa cta ctc ttt tta act gat agc cta tct gac ttt aca tct tcc 2112Asn Lys Leu Leu Phe Leu Thr Asp Ser Leu Ser Asp Phe Thr Ser Ser675 680 685ctt cgg aca ctg ctg ctg agt cat aac agg att tcc cac cta ccc tct 2160Leu Arg Thr Leu Leu Leu Ser His Asn Arg Ile Ser His Leu Pro Ser690 695 700ggc ttt ctt tct gaa gtc agt agt ctg aag cac ctc gat tta agt tcc 2208Gly Phe Leu Ser Glu Val Ser Ser Leu Lys His Leu Asp Leu Ser Ser705 710 715aat ctg cta aaa aca atm aac aaa tcc gca ctt gaa act aag acc acc 2256Asn Leu Leu Lys Thr Xaa Asn Lys Ser Ala Leu Glu Thr Lys Thr Thr720 725 730 735acc aaa tta tct atg ttg gaa cta cac gga aac ccc ttt gaa tgc acc 2304Thr Lys Leu Ser Met Leu Glu Leu His Gly Asn Pro Phe Glu Cys Thr740 745 750tgt gac att gga gat ttc cga aga tgg atg gat gaa cat ctg aat gtc 2352Cys Asp Ile Gly Asp Phe Arg Arg Trp Met Asp Glu His Leu Asn Val755 760 765aaa att ccc aga ctg gta gat gtc att tgt gcc agt cct ggg gat caa 2400Lys Ile Pro Arg Leu Val Asp Val Ile Cys Ala Ser Pro Gly Asp Gln770 775 780aga ggg aag agt att gtg agt ctg gag cta aca act tgt gtt tca gat 2448Arg Gly Lys Ser Ile Val Ser Leu Glu Leu Thr Thr Cys Val Ser Asp785 790 795gtc act gca gtg ata tta ttt ttc ttc acg ttc ttt atc acc acc atg 2496Val Thr Ala Val Ile Leu Phe Phe Phe Thr Phe Phe Ile Thr Thr Met800 805 810 815gtt atg ttg gct gcc ctg gct cac cat ttg ttt tac tgg gat gtt tgg 2544Val Met Leu Ala Ala Leu Ala His His Leu Phe Tyr Trp Asp Val Trp820 825 830
ttt ata tat aat gtg tgt tta gct aag tta aaa ggc tac agg tct ctt 2592Phe Ile Tyr Asn Val Cys Leu Ala Lys Leu Lys Gly Tyr Arg Ser Leu835 840 845tcc aca tcc caa act ttc tat gat gct tac att tct tat gac acc aaa 2640Ser Thr Ser Gln Thr Phe Tyr Asp Ala Tyr Ile Ser Tyr Asp Thr Lys850 855 860gat gcc tct gtt act gac tgg gtg ata aat gag ctg cgc tac cac ctt 2688Asp Ala Ser Val Thr Asp Trp Val Ile Asn Glu Leu Arg Tyr His Leu865 870 875gaa gag agc cga gac aaa aac gtt ctc ctt tgt cta gag gag agg gat 2736Glu Glu Ser Arg Asp Lys Asn Val Leu Leu Cys Leu Glu Glu Arg Asp880 885 890 895tgg gac ccg gga ttg gcc atc atc gac aac ctc atg cag agc atc aac 2784Trp Asp Pro Gly Leu Ala Ile Ile Asp Asn Leu Met Gln Set Ile Asn900 905 910caa agc aag aaa aca gta ttt gtt tta acc aaa aaa tat gca aaa agc 2832Gln Ser Lys Lys Thr Val Phe Val Leu Thr Lys Lys Tyr Ala Lys Ser915 920 925tgg aac ttt aaa aca gct ttt tac ttg gcc ttg cag agg cta atg ggt 2880Trp Asn Phe Lys Thr Ala Phe Tyr Leu Ala Leu Gln Arg Leu Met Gly930 935 940gag aac atg gat gtg att ata ttt atc ctg ctg gag cca gtg tta cag 2928Glu Asn Met Asp Val Ile Ile Phe Ile Leu Leu Glu Pro Val Leu Gln945 950 955cat tct ccg tat ttg agg cta cgg cag cgg atc tgt aag agc tcc atc 2976His Ser Pro Tyr Leu Arg Leu Arg Gln Arg Ile Cys Lys Set Set Ile960 965 970 975ctc cag tgg cct gac aac ccg aag gca gaa ggc ttg ttt tgg caa act 3024Leu Gln Trp Pro Asp Asn Pro Lys Ala Glu Gly Leu Phe Trp Gln Thr980 985 990ctg aga aat gtg gtc ttg act gaa aat gat tca cgg tat aac aat atg 3072Leu Arg Asn Val Val Leu Thr Glu Asn Asp Ser Arg Tyr Asn Asn Met995 10001005tat gtc gat tcc att aag caa tac taa 3099Tyr Val Asp Ser Ile Lys Gln Tyr1010 1015
MLTCIFLLISGSCELCAEENFSRSYPCDEKKQNDSVIAECSNRRLQEVPQTVGKYVTELDLSDNFITHITNESFQGLQNLTKINLNHNPNVQHQNGNPGIQSNGLNITDGAFLNLKNLRELLLEDNQLPQIPSGLPESLTELSLIQNNIYNITKEGISRLINLKNLYLAWNCYFNKVCEKTNIEDGVFETLTNLELLSLSFNSLSHVPPKLPSSLRKLFLSNTQIKYISEEDFKGLINLTLLDLSGNCPRCFNAPFPCVPCDGGASINIDRFAFQNLTQLRYLNLSSTSLRKINAAWFKNMPHLKVLDLEFNYLVGEIASGAFLTMLPRLEILDLSFNYIKGSYPQHINISRNFSKLLSLRALHLRGYVFQELREDDFQPLMQLPNLSTINLGINFIKQIDFKLFQNFSNLEIIYLSENRISPLVKDTRQSYANSSSFQRHIRKRRSTDFEFDPHSNFYHFTRPLIKPQCAAYGKALDLSLNSIFFIGPNQFENLPDIACLNLSANSNAQVLSGTEFSAIPHVKYLDLTNNRLDFDNASALTELSDLEVLDLSYNSHYFRIAGVTHHLEFIQNFTNLKVLNLSHNNIYTLTDKYNLESKSLVELVFSGNRLDILWNDDDNRYISIFKGLKNLTRLDLSLNRLKHIPNEAFLNLPASLTELHINDNMLKFFNWTLLQQFPRLELLDLRGNKLLFLTDSLSDFTSSLRTLLLSHNRISHLPSGFLSEVSSLKHLDLSSNLLKTINKSALETKTTTKLSMLELHGNPFECTCDIGDFRRWMDEHLNVKIPRLVDVICASPGDQRGKSIVSLELTTCVSDVTAVILFFFTFFITTMVMLAALAHHLFYWDVWFIYNVCLAKLKGYRSLSTSQTFYDAYISYDTKDASVTDWVINELRYHLEESRDKNVLLCLEERDWDPGLAIIDNLMQSINQSKKTVFVLTKKYAKSWNFKTAFYLALQRLMGENMDVIIFILLEPVLQHSPYLRLRQRICKSSILQWPDNPKAEGLFWQTLRNVVLTENDSRYNNMYVDSIKQY
表8诸如灵长类动物或人等哺乳动物的DNAX Toll样受体8(DTLR8)的部分核苷酸序列和氨基酸序列(见SEQ ID NO19和20)。
AAT GAA TTG ATC CCC AAT CTA GAG AAG GAA GAT GGT TCT ATC TTG ATT48Asn Glu Leu Ile Pro Asn Leu Glu Lys Glu Asp Gly Ser Ile Leu Ile1 5 10 15TGC CTT TAT GAA AGC TAC TTT GAC CCT GGC AAA AGC ATT AGT GAA AAT96Cys Leu Tyr Glu Ser Tyr Phe Asp Pro Gly Lys Ser Ile Ser Glu Asn20 25 30ATT GTA AGC TTC ATT GAG AAA AGC TAT AAG TCC ATC TTT GTT TTG TCC 144Ile Val Ser Phe Ile Glu Lys Ser Tyr Lys Ser Ile Phe Val Leu Ser35 40 45CCC AAC TTT GTC CAG AAT GAG TGG TGC CAT TAT GAA TTC TAC TTT GCC 192Pro Asn Phe Val Gln Asn Glu Trp Cys His Tyr Glu Phe Tyr Phe Ala50 55 60CAC CAC AAT CTC TTC CAT GAA AAT TCT GAT CAC ATA ATT CTT ATC TTA 240His His Asn Leu Phe His Glu Asn Ser Asp His Ile Ile Leu Ile Leu65 70 75 80CTG GAA CCC ATT CCA TTC TAT TGC ATT CCC ACC AGG TAT CAT AAA CTG 288Leu Glu Pro Ile Pro Phe Tyr Cys Ile Pro Thr Arg Tyr His Lys Leu85 90 95GAA GCT CTC CTG GAA AAA AAA GCA TAC TTG GAA TGG CCC AAG GAT AGG 336Glu Ala Leu Leu Glu Lys Lys Ala Tyr Leu Glu Trp Pro Lys Asp Arg100 105 110CGT AAA TGT GGG CTT TTC TGG GCA AAC CTT CGA GCT GCT GTT AAT GTT 384Arg Lys Cys Gly Leu Phe Trp Ala Asn Leu Arg Ala Ala Val Asn Val115 120 125AAT GTA TTA GCC ACC AGA GAA ATG TAT GAA CTG CAG ACA TTC ACA GAG 432Asn Val Leu Ala Thr Arg Glu Met Tyr Glu Leu Gln Thr Phe Thr Glu130 135 140TTA AAT GAA GAG TCT CGA GGT TCT ACA ATC TCT CTG ATG AGA ACA GAC 480Leu Asn Glu Glu Ser Arg Gly Ser Thr Ile Ser Leu Met Arg Thr Asp145 150 155 160TGT CTA TAAAATCCCA CAGTCCTTGG GAAGTTGGGG ACCACATACA CTGTTGGGAT536Cys LeuGTACATTGAT ACAACCTTTA TGATGGCAAT TTGACAATAT TTATTAAAAT AAAAAATGGT 596TATTCCCTTC AAAAAAAAAA AAAAAAAAAA AAA 629NELIPNLEKEDGSILICLYESYFDPGKSISENIVSFIEKSYKSIFVLSPNFVQNEWCHYEFYFAHHNLFHENSHIILILLEPIPFYCIPTRYHKLEALLEKKAYLEWPKDRRKCGLFWANLRAAVNVNVLATREMYELQTFTELNESRGSTISLMRTDCL
诸如人等灵长类动物的附加序列(SEQ ID NO31和32)；用C表示的第4和23位核苷酸可以是A、C、G或T；用C表示的第845位核苷酸可以是C或TC TCC GAT GCC AAG ATT CGG CAC CAG GCA TAT TCA GAG GTC ATG ATG 46Ser Asp Ala Lys Ile Arg His Gln Ala Tyr Ser Glu Val Met Met1 5 10 15GTT GGA TGG TCA GAT TCA TAC ACC TGT GAA TAC CCT TTA AAC CTA AGG 94Val Gly Trp Ser Asp Ser Tyr Thr Cys Glu Tyr Pro Leu Asn Leu Arg20 25 30GGA ACT AGG TTA AAA GAC GTT CAT CTC CAC GAA TTA TCT TGC AAC ACA142Gly Thr Arg Leu Lys Asp Val His Leu His Glu Leu Ser Cys Asn Thr35 40 45GCT CTG TTG ATT GTC ACC ATT GTG GTT ATT ATG CTA GTT CTG GGG TTG190Ala Leu Leu Ile Val Thr Ile Val Val Ile Met Leu Val Leu Gly Leu50 55 60GCT GTG GCC TTC TGC TGT CTC CAC TTT GAT CTG CCC TGG TAT CTC AGG238Ala Val Ala Phe Cys Cys Leu His Phe Asp Leu Pro Trp Tyr Leu Arg65 70 75ATG CTA GGT CAA TGC ACA CAA ACA TGG CAC AGG GTT AGG AAA ACA ACC286Met Leu Gly Gln Cys Thr Gln Thr Trp His Arg Val Arg Lys Thr Thr80 85 90 95CAA GAA CAA CTC AAG AGA AAT GTC CGA TTC CAC GCA TTT ATT TCA TAC334Gln Glu Gln Leu Lys Arg Asn Val Arg Phe His Ala Phe Ile Ser Tyr100 105 110AGT GAA CAT GAT TCT CTG TGG GTG AAG AAT GAA TTG ATC CCC AAT CTA382Ser Glu His Asp Ser Leu Trp Val Lys Asn Glu Leu Ile Pro Asn Leu115 120 125GAG AAG GAA GAT GGT TCT ATC TTG ATT TGC CTT TAT GAA AGC TAC TTT430Glu Lys Glu Asp Gly Ser Ile Leu Ile Cys Leu Tyr Glu Ser Tyr Phe130 135 140GAC CCT GGC AAA AGC ATT AGT GAA AAT ATT GTA AGC TTC ATT GAG AAA478Asp Pro Gly Lys Ser Ile Ser Glu Asn Ile Val Ser Phe Ile Glu Lys145 150 155AGC TAT AAG TCC ATC TTT GTT TTG TCT CCC AAC TTT GTC CAG AAT GAG526Ser Tyr Lys Ser Ile Phe Val Leu Ser Pro Asn Phe Val Gln Asn Glu160 165 170 175TGG TGC CAT TAT GAA TTC TAC TTT GCC CAC CAC AAT CTC TTC CAT GAA574Trp Cys His Tyr Glu Phe Tyr Phe Ala His His Asn Leu Phe His Glu180 185 190AAT TCT GAT CAC ATA ATT CTT ATC TTA CTG GAA CCC ATT CCA TTC TAT622Asn Ser Asp His Ile Ile Leu Ile Leu Leu Glu Pro Ile Pro Phe Tyr195 200 205
TGC ATT CCC ACC AGG TAT CAT AAA CTG GAA GCT CTC CTG GAA AAA AAA670Cys Ile Pro Thr Arg Tyr His Lys Leu Glu Ala Leu Leu Glu Lys Lys210 215 220GCA TAC TTG GAA TGG CCC AAG GAT AGG CGT AAA TGT GGG CTT TTC TGG718Ala Tyr Leu Glu Trp Pro Lys Asp Arg Arg Lys Cys Gly Leu Phe Trp225 230 235GCA AAC CTT CGA GCT GCT GTT AAT GTT AAT GTA TTA GCC ACC AGA GAA766Ala Asn Leu Arg Ala Ala Val Asn Val Asn Val Leu Ala Thr Arg Glu240 245 250 255ATG TAT GAA CTG CAG ACA TTC ACA GAG TTA AAT GAA GAG TCT CGA GGT814Met Tyr Glu Leu Gln Thr Phe Thr Glu Leu Asn Glu Glu Ser Arg Gly260 265 270TCT ACA ATC TCT CTG ATG AGA ACA GAC TGT CTA TAAAATCCCA CAGTCCTTGG 867Ser Thr Ile Ser Leu Met Arg Thr Asp Cys Leu275 280GAAGTTGGGG ACCACATACA CTGTTGGGAT GTACATTGAT ACAACCTTTA TGATGGCAAT 927TTGACAATAT TTATTAAAAT AAAAAATGGT TATTCCCTTC AAAAAAAAAA AAAAAAAAAA 987AAAAAAAAAA AA 999SDAKIRHQAYSEVMMVGWSDSYTCEYPLNLRGTRLKDVHLHELSCNTALLIVTIVVIMLVLGLAVAFCCLHFDKWYLRMLGQCTQTWHRVRKTTQEQLKRNVRFHAFISYSEHDSLWVKNELIPNLEKEDGSILICLYESYFDPGKSTENIVSFIEKSYKSIFVLSPNFVQNEWCHYEFYFAHHNLFHENSDHIILILLEPIPFYCIPTRYHKLEALLEKKALEWPKDRRKCGLFWANLRAAVNVNVLATREMYELQTFTELNEESRGSTISLMRTDCL诸如人等灵长类动物的DTLR8的其他序列(SEQ ID NO38和39)gaatcatcca cgcacctgca gctctgctga gagagtgcaa gccgtggggg ttttgagctc 60atcttcatca ttcatatgag gaaataagtg gtaaaatcct tggaaataca atg aga 116Met Argctc atc aga aac att tac ata ttt tgt agt att gtt atg aca gca gag164Leu Ile Arg Asn Ile Tyr Ile Phe Cys Ser Ile Val Met Thr Ala Glu-15 -10 -5ggt gat gct cca gag ctg cca gaa gaa agg gaa ctg atg acc aac tgc212Gly Asp Ala Pro Glu Leu Pro Glu Glu Arg Glu Leu Met Thr Asn Cys-1 1 5 10 15tcc aac atg tct cta aga aag gtt ccc gca gac ttg acc cca gcc aca260Ser Asn Met Ser Leu Arg Lys Val Pro Ala Asp Leu Thr Pro Ala Thr20 25 30acg aca ctg gat tta tcc tat aac ctc ctt ttt caa ctc cag agt tca308Thr Thr Leu Asp Leu Ser Tyr Asn Leu Leu Phe Gln Leu Gln Set Set35 40 45
gat ttt cat tct gtc tcc aaa ctg aga gtt ttg att cta tgc cat aac 356Asp Phe His Ser Val Ser Lys Leu Arg Val Leu Ile Leu Cys His Asn50 55 60aga att caa cag ctg gat ctc aaa acc ttt gaa ttc aac aag gag tta 404Arg Ile Gln Gln Leu Asp Leu Lys Thr Phe Glu Phe Asn Lys Glu Leu65 70 75aga tat tta gat ttg tct aat aac aga ctg aag agt gta act tgg tat 452Arg Tyr Leu Asp Leu Ser Asn Asn Arg Leu Lys Ser Val Thr Trp Tyr80 85 90 95tta ctg gca ggt ctc agg tat tta gat ctt tct ttt aat gac ttt gac 500Leu Leu Ala Gly Leu Arg Tyr Leu Asp Leu Ser Phe Asn Asp Phe Asp100 105 110acc atg cct atc tgt gag gaa gct ggc aac atg tca cac ctg gaa atc 548Thr Met Pro Ile Cys Glu Glu Ala Gly Asn Met Ser His Leu Glu Ile115 120 125cta ggt ttg agt ggg gca aaa ata caa aaa tca gat ttc cag aaa att 596Leu Gly Leu Ser Gly Ala Lys Ile Gln Lys Ser Asp Phe Gln Lys Ile130 135 140gct cat ctg cat cta aat act gtc ttc tta gga ttc aga act ctt cct 644Ala His Leu His Leu Asn Thr Val Phe Leu Gly Phe Arg Thr Leu Pro145 150 155cat tat gaa gaa ggt agc ctg ccc atc tta aac aca aca aaa ctg cac 692His Tyr Glu Glu Gly Ser Leu Pro Ile Leu Asn Thr Thr Lys Leu His160 165 170 175att gtt tta cca atg gac aca aat ttc tgg gtt ctt ttg cgt gat gga 740Ile Val Leu Pro Met Asp Thr Asn Phe Trp Val Leu Leu Arg Asp Gly180 185 190atc aag act tca aaa ata tta gaa atg aca aat ata gat ggc aaa agc 788Ile Lys Thr Ser Lys Ile Leu Glu Met Thr Asn Ile Asp Gly Lys Ser195 200 205caa ttt gta agt tat gaa atg caa cga aat ctt agt tta gaa aat gct 836Gln Phe Val Ser Tyr Glu Met Gln Arg Asn Leu Ser Leu Glu Asn Ala210 215 220aag aca tcg gtt cta ttg ctt aat aaa gtt gat tta ctc tgg gac gac 884Lys Thr Ser Val Leu Leu Leu Asn Lys Val Asp Leu Leu Trp Asp Asp225 230 235ctt ttc ctt atc tta caa ttt gtt tgg cat aca tca gtg gaa cac ttt 932Leu Phe Leu Ile Leu Gln Phe Val Trp His Thr Ser Val Glu His Phe240 245 250 255cag atc cga aat gtg act ttt ggt ggt aag gct tat ctt gac cac aat 980Gln Ile Arg Asn Val Thr Phe Gly Gly Lys Ala Tyr Leu Asp His Asn260 265 270
tca ttt gac tac tca aat act gta atg aga act ata aaa ttg gag cat 1028Ser Phe Asp Tyr Ser Asn Thr Val Met Arg Thr Ile Lys Leu Glu His275 280 285gta cat ttc aga gtg ttt tac att caa cag gat aaa atc tat ttg ctt 1076Val His Phe Arg Val Phe Tyr Ile Gln Gln Asp Lys Ile Tyr Leu Leu290 295 300ttg acc aaa atg gac ata gaa aac ctg aca ata tca aat gca caa atg 1124Leu Thr Lys Met Asp Ile Glu Asn Leu Thr Ile Set Asn Ala Gln Met305 310 315cca cac atg ctt ttc ccg aat tat cct acg aaa ttc caa tat tta aat 1172Pro His Met Leu Phe Pro Asn Tyr Pro Thr Lys Phe Gln Tyr Leu Asn320 325 330 335ttt gcc aat aat atc tta aca gac gag ttg ttt aaa aga act atc caa 1220Phe Ala Asn Asn Ile Leu Thr Asp Glu Leu Phe Lys Arg Thr Ile Gln340 345 350ctg cct cac ttg aaa act ctc att ttg aat ggc aat aaa ctg gag aca 1268Leu Pro His Leu Lys Thr Leu Ile Leu Asn Gly Asn Lys Leu Glu Thr355 360 365ctt tct tta gta agt tgc ttt gct aac aac aca ccc ttg gaa cac ttg 1316Leu Ser Leu Val Ser Cys Phe Ala Asn Asn Thr Pro Leu Glu His Leu370 375 380gat ctg agt caa aat cta tta caa cat aaa aat gat gaa aat tgc tca 1364Asp Leu Ser Gln Asn Leu Leu Gln His Lys Asn Asp Glu Asn Cys Ser385 390 395tgg cca gaa act gtg gtc aat atg aat ctg tca tac aat aaa ttg tct 1412Trp Pro Glu Thr Val Val Asn Met Asn Leu Ser Tyr Asn Lys Leu Ser400 405 410 415gat tct gtc ttc agg tgc ttg ccc aaa agt att caa ata ctt gac cta 1460Asp Ser Val Phe Arg Cys Leu Pro Lys Ser Ile Gln Ile Leu Asp Leu420 425 430aat aat aac caa atc caa act gta cct aaa gag act att cat ctg atg 1508Asn Asn Asn Gln Ile Gln Thr Val Pro Lys Glu Thr Ile His Leu Met435 440 445gcc tta cga gaa cta aat att gca ttt aat ttt cta act gat ctc cct 1556Ala Leu Arg Glu Leu Asn Ile Ala Phe Asn Phe Leu Thr Asp Leu Pro450 455 460gga tgc agt cat ttc agt aga ctt tca gtt ctg aac att gaa atg aac 1604Gly Cys Ser His Phe Ser Arg Leu Ser Val Leu Asn Ile Glu Met Asn465 470 475ttc att ctc agc cca tct ctg gat ttt gtt cag agc tgc cag gaa gtt 1652Phe Ile Leu Ser Pro Ser Leu Asp Phe Val Gln Ser Cys Gln Glu Val480 485 490 495
aaa act cta aat gcg gga aga aat cca ttc cgg tgt acc tgt gaa tta 1700Lys Thr Leu Asn Ala Gly Arg Asn Pro Phe Arg Cys Thr Cys Glu Leu500 505 510aaa aat ttc att cag ctt gaa aca tat tca gag gtc atg atg gtt gga 1748Lys Asn Phe Ile Gln Leu Glu Thr Tyr Ser Glu Val Met Met Val Gly515 520 525tgg tca gat tca tao acc tgt gaa tac cct tta aac cta agg gga act 1796Trp Ser Asp Ser Tyr Thr Cys Glu Tyr Pro Leu Asn Leu Arg Gly Thr530 535 540agg tta aaa gac gtt cat ctc cac gaa ttatct tgc aac aca gct ctg1844Arg Leu Lys Asp Val His Leu His Glu Leu Ser Cys Asn Thr Ala Leu545 550 555ttg att gtc acc att gtg gtt att atg cta gtt ctg ggg ttg gct gtg 1892Leu Ile Val Thr Ile Val Val Ile Met Leu Val Leu Gly Leu Ala Val560 565 570 575gcc ttc tgc tgt ctc cac ttt gat ctg ccc tgg tat ctc agg atg cta 1940Ala Phe Cys Cys Leu His Phe Asp Leu Pro Trp Tyr Leu Arg Met Leu580 585 590ggt caa tgc aca caa aca tgg cac agg gtt agg aaa aca acc caa gaa 1988Gly Gln Cys Thr Gln Thr Trp His Arg Val Arg Lys Thr Thr Gln Glu595 600 605caa ctc aag aga aat gtc cga ttc cac gca ttt att tca tac agt gaa 2036Gln Leu Lys Arg Asn Val Arg Phe His Ala Phe Ile Ser Tyr Ser Glu610 615 620cat gat tct ctg tgg gtg aag aat gaa ttg atc ccc aat cta gag aag 2084His Asp Ser Leu Trp Val Lys Asn Glu Leu Ile Pro Asn Leu Glu Lys625 630 635gaa gat ggt tct atc ttg att tgc ctt tat gaa agc tac ttt gac cct 2132Glu Asp Gly Ser Ile Leu Ile Cys Leu Tyr Glu Ser Tyr Phe Asp Pro640 645 650 655ggc aaa agc att agt gaa aat att gta agc ttc att gag aaa agc tat 2180Gly Lys Ser Ile Ser Glu Asn Ile Val Ser Phe Ile Glu Lys Ser Tyr660 665 670aag tcc atc ttt gtt ttg tct ccc aac ttt gtc cag aat gag tgg tgc 2228Lys Ser Ile Phe Val Leu Ser Pro Asn Phe Val Gln Asn Glu Trp Cys675 680 685cat tat gaa ttc tac ttt gcc cac cac aat ctc ttc cat gaa aat tct 2276His Tyr Glu Phe Tyr Phe Ala His His Asn Leu Phe His Glu Asn Ser690 695 700gat cat ata att ctt atc tta ctg gaa ccc att cca ttc tat tgc att 2324Asp His Ile Ile Leu Ile Leu Leu Glu Pro Ile Pro Phe Tyr Cys Ile705 710 715
ccc acc agg tat cat aaa ctg aaa gct ctc ctg gaa aaa aaa gca tac 2372Pro Thr Arg Tyr His Lys Leu Lys Ala Leu Leu Glu Lys Lys Ala Tyr720 725 730 735ttg gaa tgg ccc aag gat agg cgt aaa tgt ggg ctt ttc tgg gca aac 2420Leu Glu Trp Pro Lys Asp Arg Arg Lys Cys Gly Leu Phe Trp Ala Asn740 745 750ctt cga gct gct att aat gtt aat gta tta gcc acc aga gaa atg tat 2468Leu Arg Ala Ala Ile Asn Val Asn Val Leu Ala Thr Arg Glu Met Tyr755 760 765gaa ctg cag aca ttc aca gag tta aat gaa gag tct cga ggt tct aca 2516Glu Leu Gln Thr Phe Thr Glu Leu Asn Glu Glu Ser Arg Gly Ser Thr770 775 780atc tct ctg atg aga aca gat tgt cta taaaatccca cagtccttgg 2563Ile Ser Leu Met Arg Thr Asp Cys Leu785 790gaagttgggg accacataca ctgttgggat gtacattgat acaaccttta tgatggcaat 2623ttgacaatat ttattaaaat aaaaaatggt tattcccttc atatcagttt ctagaaggat 2683ttctaagaat gtatcctata gaaacacctt cacaagttta taagggctta tggaaaaagg 2743tgttcatccc aggattgttt ataatcatga aaaatgtggc caggtgcagt ggctcactct 2803tgtaatccca gcactatggg aggccaaggt gggtgaccca cgaggtcaag agatggagac 2863catcctggcc aacatggtga aaccctgtct ctactaaaaa tacaaaaatt agctgggcgt 2923gatggtgcac gcctgtagtc ccagctactt gggaggctga ggcaggagaa tcgcttgaac 2983ccgggaggtg gcagttgcag tgagctgaga tcgagccact gcactccagc ctggtgacag 3043agc 3046MRLIRNIYIFCSIVMTAEGDAPELPEERELMTNCSNMSLRKVPADLTPATTTLDLSYNLLFQLQSSDFHSVSKLRVLILCHNRIQQLDLKTFEFNKELRYLDLSNNRLKSVTWYLLAGLRYLDLSFNDFDTMPICEEAGNMSHLEILGLSGAKIQKSDFQKIAHLHLNTVFLGFRTLPHYEEGSLPILNTTKLHIVLPMDTNFWVLLRDGIKTSKILEMTNIDGKSQFVSYEMQRNLSLENAKTSVLLLNKVDLLWDDLFLILQFVWHTSVEHFQIRNVTFGGKAYLDHNSFDYSNTVMRTIKLEHVHFRVFYIQQDKIYLLLTKMDIENLTISNAQMPHMLFPNYPTKFQYLNFANNILTDELFKRTIQLPHLKTLILNGNKLETLSLVSCFANNTPLEHLDLSQNLLQHKNDENCSWPETVVNMNLSYNKLSDSVFRCLPKSIQILDLNNNQIQTVPKETIHLMALRELNIAFNFLTDLPGCSHFSRLSVLNIEMNFILSPSLDFVQSCQEVKTLNAGRNPFRCTCELKNFIQLETYSEVMMVGWSDSYTCEYPLNLRGTRLKDVHLHELSCNTALLIVTIVVIMLVLGLAVAFCCLHFDLPWYLRMLGQCTQTWHRVRKTTQEQLKRNVRFHAFISYSEHDSLWVKNELIPNLEKEDGSILICLYESYFDPGKSISENIVSFIEKSYKSIFVLSPNFVQNEWCHYEFYFAHHNLFHENSDHIILILLEPIPFYCIPTRYHKLKALLEKKAYLEWPKDRRKCGLFWANLRAAINVNVLATREMYELQTFTELNEESRGSTISLMRTDCL
表9诸如灵长类动物或人等哺乳动物的DNAX Toll样受体9(DTLR9)的部分核苷酸序列和氨基酸序列(见SEQ ID NO21和22)。
AAG AAC TCC AAA GAA AAC CTC CAG TTT CAT GCT TTT ATT TCA TAT AGT 48Lys Asn Ser Lys Glu Asn Leu Gln Phe His Ala Phe Ile Ser Tyr Ser1 5 10 15GAA CAT GAT TCT GCC TGG GTG AAA AGT GAA TTG GTA CCT TAC CTA GAA 96Glu His Asp Ser Ala Trp Val Lys Ser Glu Leu Val Pro Tyr Leu Glu20 25 30AAA GAA GAT ATA CAG ATT TGT CTT CAT GAG AGA AAC TTT GTC CCT GGC144Lys Glu Asp Ile Gln Ile Cys Leu His Glu Arg Asn Phe Val Pro Gly35 40 45AAG AGC ATT GTG GAA AAT ATC ATC AAC TGC ATT GAG AAG AGT TAC AAG192Lys Ser Ile Val Glu Asn Ile Ile Asn Cys Ile Glu Lys Ser Tyr Lys50 55 60TCC ATC TTT GTT TTG TCT CCC AAC TTT GTC CAG AGT GAG TGG TGC CAT240Ser Ile Phe Val Leu Ser Pro Asn Phe Val Gln Ser Glu Trp Cys His65 70 75 80TAC GAA CTC TAT TTT GCC CAT CAC AAT CTC TTT CAT GAA GGA TCT AAT288Tyr Glu Leu Tyr Phe Ala His His Asn Leu Phe His Glu Gly Ser Asn85 90 95AAC TTA ATC CTC ATC TTA CTG GAA CCC ATT CCA CAG AAC AGC ATT CCC336Asn Leu Ile Leu Ile Leu Leu Glu Pro Ile Pro Gln Asn Ser Ile Pro100 105 110AAC AAG TAC CAC AAG CTG AAG GCT CTC ATG ACG CAG CGG ACT TAT TTG384Asn Lys Tyr His Lys Leu Lys Ala Leu Met Thr Gln Arg Thr Tyr Leu115 120 125CAG TGG CCC AAG GAG AAA AGC AAA CGT GGG CTC TTT TGG GCT426Gln Trp Pro Lys Glu Lys Ser Lys Arg Gly Leu Phe Trp Ala130 135 140A 427KNSKENLQFHAFISYSEHDSAWVKSELVPYLEKEDIQICLHERNFVPGKSIVENIINCIEKSYKSIFVLSPNESEWCHYELYFAHHNLFHEGSNNLILILLEPIPQNSIPNKYHKLKALMTQRTYLQWPKEKSKRGLFWA
诸如人等灵长类动物的DTLR9的其他序列(SEQ ID NO40和41)aagaatttgg actcatatca agatgctctg aagaagaaca accctttagg atagccactg60caacatc atg acc aaa gac aaa gaa cct att gtt aaa agc ttc cat ttt 109Met Thr Lys Asp Lys Glu Pro Ile Val Lys Ser Phe His Phe-30 -25 -20gtt tgc ctt atg atc ata ata gtt gga acc aga atc cag ttc tcc gac 157Val Cys Leu Met Ile Ile Ile Val Gly Thr Arg Ile Gln Phe Ser Asp-15 -10 -5gga aat gaa ttt gca gta gac aag tca aaa aga ggt ctt att cat gtt 205Gly Asn Glu Phe Ala Val Asp Lys Ser Lys Arg Gly Leu Ile His Val-11 5 10 15cca aaa gac cta ccg ctg aaa acc aaa gtc tta gat atg tct cag aac 253Pro Lys Asp Leu Pro Leu Lys Thr Lys Val Leu Asp Met Ser Gln Asn20 25 30rac atc gct gag ctt cag gtc tct gac atg agc ttt cta tca gag ttg 301Tyr Ile Ala Glu Leu Gln Val Ser Asp Met Ser Phe Leu Ser Glu Leu35 40 45aca gtt ttg aga ctt tcc cat aac aga atc cag cta ctt gat tta agt 349Thr Val Leu Arg Leu Ser His Asn Arg Ile Gln Leu Leu Asp Leu Ser50 55 60gtt ttc aag ttc aac cag gat tta gaa tat ttg gat tta tct cat aat 397Val Phe Lys Phe Asn Gln Asp Leu Glu Tyr Leu Asp Leu Ser His Asn65 70 75cag ttg caa aag ata tcc tgc cat cct att gtg agt ttc agg cat tta 445Gln Leu Gln Lys Ile Ser Cys His Pro Ile Val Ser Phe Arg His Leu80 85 90 95gat ctc tca ttc aat gat ttc aag gcc ctg ccc atc tgt aag gaa ttt 493Asp Leu Ser Phe Asn Asp Phe Lys Ala Leu Pro Ile Cys Lys Glu Phe100 105 110ggc aac tta tca caa ctg aat ttc ttg gga ttg agt gct atg aag ctg 541Gly Asn Leu Ser Gln Leu Asn Phe Leu Gly Leu Ser Ala Met Lys Leu115 120 125caa aaa tta gat ttg ctg cca att gct cac ttg cat cta agt tat atc 589Gln Lys Leu Asp Leu Leu Pro Ile Ala His Leu His Leu Set Tyr Ile130 135 140ctt ctg gat tta aga aat tat tat ata aaa gaa aat gag aca gaa agt 637Leu Leu Asp Leu Arg Asn Tyr Tyr Ile Lys Glu Asn Glu Thr Glu Ser145 150 155cta caa att ctg aat gca aaa acc ctt cac ctt gtt ttt cac cca act 685Leu Gln Ile Leu Asn Ala Lys Thr Leu His Leu Val Phe His Pro Thr160 165 170 175
agt tta ttc gct atc caa gtg aac ata tca gtt aat act tta ggg tgc733Ser Leu Phe Ala Ile Gln Val Asn Ile Ser Val Asn Thr Leu Gly Cys180 185 190tta caa ctg act aat att aaa ttg aat gat gac aac tgt caa gtt ttc781Leu Gln Leu Thr Asn Ile Lys Leu Asn Asp Asp Asn Cys Gln Val Phe195 200 205att aaa ttt tta tca gaa ctc acc aga ggt cca acc tta ctg aat ttt829Ile Lys Phe Leu Ser Glu Leu Thr Arg Gly Pro Thr Leu Leu Asn Phe210 215 220acc ctc aac cac ata gaa acg act tgg aaa tgc ctg gtc aga gtc ttt877Thr Leu Asn His Ile Glu Thr Thr Trp Lys Cys Leu Val Arg Val Phe225 230 235caa ttt ctt tgg ccc aaa cct gtg gaa tat ctc aat att tac aat tta925Gln Phe Leu Trp Pro Lys Pro Val Glu Tyr Leu Asn Ile Tyr Asn Leu240 245 250 255aca ata att gaa agc att cgt gaa gaa gat ttt act tat tct aaa acg973Thr Ile Ile Glu Ser Ile Arg Glu Glu Asp Phe Thr Tyr Ser Lys Thr260 265 270aca ttg aaa gca ttg aca ata gaa cat atc acg aac caa gtt ttt ctg 1021Thr Leu Lys Ala Leu Thr Ile Glu His Ile Thr Asn Gln Val Phe Leu275 280 285ttt tca cag aca gct ttg tac acc gtg ttt tct gag atg aac att atg 1069Phe Ser Gln Thr Ala Leu Tyr Thr Val Phe Ser Glu Met Asn Ile Met290 295 300atg tta acc att tca gat aca cct ttt ata cac atg ctg tgt cct cat 1117Met Leu Thr Ile Ser Asp Thr Pro Phe Ile His Met Leu Cys Pro His305 310 315gca cca agc aca ttc aag ttt ttg aac ttt acc cag aac gtt ttc aca 1165Ala Pro Ser Thr Phe Lys Phe Leu Asn Phe Thr Gln Asn Val Phe Thr320 325 330 335gat agt att ttt gaa aaa tgt tcc acg tta gtt aaa ttg gag aca ctt 1213Asp Ser Ile Phe Glu Lys Cys Ser Thr Leu Val Lys Leu Glu Thr Leu340 345 350atc tta caa aag aat gga tta aaa gac ctt ttc aaa gta ggt ctc atg 1261Ile Leu Gln Lys Asn Gly Leu Lys Asp Leu Phe Lys Val Gly Leu Met355 360 365acg aag gat atg cct tct ttg gaa ata ctg gat gtt agc tgg aat tct 1309Thr Lys Asp Met Pro Ser Leu Glu Ile Leu Asp Val Ser Trp Asn Ser370 375 380ttg gaa tct ggt aga cat aaa gaa aac tgc act tgg gtt gag agt ata 1357Leu Glu Ser Gly Arg His Lys Glu Asn Cys Thr Trp Val Glu Ser Ile385 390 395
gtg gtg tta aat ttg tct tca aat atg ctt act gac tct gtt ttc aga 1405Val Val Leu Asn Leu Ser Ser Asn Met Leu Thr Asp Ser Val Phe Arg400 405 410 415tgt tta cct ccc agg atc aag gta ctt gat ctt cac agc aat aaa ata 1453Cys Leu Pro Pro Arg Ile Lys Val Leu Asp Leu His Ser Asn Lys Ile420 425 430aag agc gtt cct aaa caa gtc gta aaa ctg gaa gct ttg caa gaa ctc 1501Lys Ser Val Pro Lys Gln Val Val Lys Leu Glu Ala Leu Gln Glu Leu435 440 445aat gtt gct ttc aat tct tta act gac ctt cct gga tgt ggc agc ttt 1549Asn Val Ala Phe Asn Ser Leu Thr Asp Leu Pro Gly Cys Gly Ser Phe450 455 460agc agc ctt tct gta ttg atc att gat cac aat tca gtt tcc cac cca 1597Ser Ser Leu Ser Val Leu Ile Ile Asp His Asn Ser Val Ser His Pro465 470 475tcg gct gat ttc ttc cag agc tgc cag aag atg agg tca ata aaa gca 1645Ser Ala Asp Phe Phe Gln Ser Cys Gln Lys Met Arg Ser Ile Lys Ala480 485 490 495ggg gac aat cca ttc caa tgt acc tgt gag cta aga gaa ttt gtc aaa 1693Gly Asp Asn Pro Phe Gln Cys Thr Cys Glu Leu Arg Glu Phe Val Lys500 505 510aat ata gac caa gta tca agt gaa gtg tta gag ggc tgg cct gat tct 1741Asn Ile Asp Gln Val Ser Ser Glu Val Leu Glu Gly Trp Pro Asp Ser515 520 525tat aag tgt gac tac cca gaa agt tat aga gga agc cca cta aag gac 1789Tyr Lys Cys Asp Tyr Pro Glu Ser Tyr Arg Gly Ser Pro Leu Lys Asp530 535 540ttt cac atg tct gaa tta tcc tgc aac ata act ctg ctg atc gtc acc 1837Phe His Met Ser Glu Leu Ser Cys Asn Ile Thr Leu Leu Ile Val Thr545 550 555atc ggt gcc acc atg ctg gtg ttg gct gtg act gtg acc tcc ctc tgc 1885Ile Gly Ala Thr Met Leu Val Leu Ala Val Thr Val Thr Ser Leu Cys560 565 570 575atc tac ttg gat ctg ccc tgg tat ctc agg atg gtg tgc cag tgg acc 1933Ile Tyr Leu Asp Leu Pro Trp Tyr Leu Arg Met Val Cys Gln Trp Thr580 585 590cag act cgg cgc agg gcc agg aac ata ccc tta gaa gaa ctc caa aga 1981Gln Thr Arg Arg Arg Ala Arg Asn Ile Pro Leu Glu Glu Leu Gln Arg595 600 605aac ctc cag ttt cat gct ttt att tca tat agt gaa cat gat tct gcc 2029Asn Leu Gln Phe His Ala Phe Ile Ser Tyr Ser Glu His Asp Ser Ala610 615 620
tgg gtg aaa agt gaa ttg gta cct tac cta gaa aaa gaa gat ata cag 2077Trp Val Lys Ser Glu Leu Val Pro Tyr Leu Glu Lys Glu Asp Ile Gln625 630 635att tgt ctt cat gag agg aac ttt gtc cct ggc aag agc att gtg gaa 2125Ile Cys Leu His Glu Arg Asn Phe Val Pro Gly Lys Ser Ile Val Glu640 645 650 655aat atc atc aac tgc att gag aag agt tac aag tcc atc ttt gtt ttg 2173Asn Ile Ile Asn Cys Ile Glu Lys Ser Tyr Lys Ser Ile Phe Val Leu660 665 670tct ccc aac ttt gtc cag agt gag tgg tgc cat tac gaa ctc tat ttt 2221Ser Pro Asn Phe Val Gln Ser Glu Trp Cys His Tyr Glu Leu Tyr Phe675 680 685gcc cat cac aat ctc ttt cat gaa gga tct aat aac tta atc ctc atc 2269Ala His His Asn Leu Phe His Glu Gly Ser Asn Asn Leu Ile Leu Ile690 695 700tta ctg gaa ccc att cca cag aac agc att ccc aac aag tac cac aag 2317Leu Leu Glu Pro Ile Pro Gln Asn Ser Ile Pro Asn Lys Tyr His Lys705 710 715ctg aag gct ctc atg acg cag cgg act tat ttg cag tgg ccc aag gag 2365Leu Lys Ala Leu Met Thr Gln Arg Thr Tyr Leu Gln Trp Pro Lys Glu720 725 730 735aaa agc aaa cgt ggg ctc ttt tgg gct aac att aga gcc gct ttt aat 2413Lys Ser Lys Arg Gly Leu Phe Trp Ala Asn Ile Arg Ala Ala Phe Asn740 745 750atg aaa tta aca cta gtc act gaa aac aat gat gtg aaa tct 2455Met Lys Leu Thr Leu Val Thr Glu Asn Asn Asp Val Lys Ser755 760 765taaaaaaatt taggaaattc aacttaagaa accattattt acttggatga tggtgaatag 2515tacagtcgta agtnactgtc tggaggtgcc tccattatcc tcatgccttc aggaaagact 2575taacaaaaac aatgtttcat ctggggaact gagctaggcg gtgaggttag cctgccagtt 2635agagacagcc cagtctcttc tggtttaatc attatgtttc aaattgaaac agtctctttt 2695gagtaaatgc tcagtttttc agctcctctc cactctgctt tcccaaatgg attctgttgg 2755tgaag 2760
MTKDKEPIVKSFHFVCLMIIIVGTRIQFSDGNEFAVDKSKRGLIHVPKDLPLKTKVLDMSQNYIAELQVSDMSFLSELTVLRLSHNRIQLLDLSVFKFNQDLEYLDLSHNQLQKISCHPIVSFRHLDLSFNDFKALPICKEFGNLSQLNFLGLSAMKLQKLDLLPIAHLHLSYILLDLRNYYIKENRTESLQILNAKTLHLVFHPTSLFAIQVNISVNTLGCLQLTNIKLNDDNCQVFIKFLSELTRGPTLLNFTLNHIETTWKCLVRVFQFLWPKPVEYLNIYNLTIIESIREEDFTYSKTTLKALTIEHITNQVFLFSQTALYTVFSEMNIMMLTISDTPFIHMLCPHAPSTFKFLNFTQNVFTDSIFEKCSTLVKLETLILQKNGLKDLFKVGLMTKDMPSLEILDVSWNSLESGRHKENCTWVESIVVLNLSSMMLTDSVFRCLPPRIKVLDLHSNKIKSVPKQVVKLEALQELNVAFNSLTDLPGCGSFSSLSVLIIDHNSVSHPSADFFQSCQKMRSIKAGDNPFQCTCELREFVKNIDQVSSEVLEGWPDSYKCDYPESYRGSPLKDFHMSELSCNITLLIVTIGATMLVLAVTVTSLCIYLDLPWYLRMVCQWTQTRRRARNIPLEELQRNLQFHAFISYSEHDSAWVKSELVPYLEKEDIQICLHERNFVPGKSIVENIINCIEKSYKSIFVLSPNFVQSEWCHYELYFAHHNLFHEGSNNLILILLEPIPQNSIPNKYHKLKALMTQRTYLQWPKEKSKRGLFWANIRAAFNMKLTLVTENNDVKS
表10诸如灵长类动物或人等哺乳动物的DNAX Toll样受体10(DTLR10)的核苷酸序列和氨基酸序列(见SEQ ID NO23和24)。用A表示的第54、103和345位核苷酸的每个都可以是A或G；用G表示的第313位核苷酸可以是G或T；并且用C表示的第316、380、407和408位核苷酸的每个都可以是A、C、G或T。
GCT TCC ACC TGT GCC TGG CCT GGC TTC CCT GGC GGG GGC GGC AAA GTG 48Ala Ser Thr Cys Ala Trp Pro Gly Phe Pro Gly Gly Gly Gly Lys Val1 5 10 15GGC GAA ATG AGG ATG CCC TGC CCT ACG ATG CCT TCG TGG TCT TCG ACA 96Gly Glu Met Arg Met Pro Cys Pro Thr Mer Pro Ser Trp Ser Ser Thr20 25 30AAA CGC AGA GCG CAG TGG CAG ACT GGG TGT ACA ACG AGC TTC GGG GGC144Lys Arg Arg Ala Gln Trp Gln Thr Gly Cys Thr Thr Ser Phe Gly Gly35 40 45AGC TGG AGG AGT GCC GTG GGC GCT GGG CAC TCC GCC TGT GCC TGG AGG192Ser Trp Arg Ser Ala Val Gly Ala Gly His Ser Ala Cys Ala Trp Arg50 55 60AAC GCG ACT GGC TGC CTG GCA AAA CCC TCT TTG AGA ACC TGT GGG CCT240Asn Ala Thr Gly Cys Leu Ala Lys Pro Ser Leu Arg Thr Cys Gly Pro65 70 75 80CGG TCT ATG GCA GCC GCA AGA CGC TGT TTG TGC TGG CCC ACA CGG ACC288Arg Ser Met Ala Ala Ala Arg Arg Cys Leu Cys Trp Pro Thr Arg Thr85 90 95GGG TCA GTG GTC TCT TGC GCG CCA GTT CTC CTG CTG GCC CAG CAG CGC336Gly Ser Val Val Ser Cys Ala Pro Val Leu Leu Leu Ala Gln Gln Arg100 105 110CTG CTG GAA GAC CGC AAG GAC GTC GTG GTG CTG GTG ATC CTA ACG CCT384Leu Leu Glu Asp Arg Lys Asp Val Val Val Leu Val Ile Leu Thr Pro115 120 125GAC GGC CAA GCC TCC CGA CTA CCC GAT GCG CTG ACC AGC GCC TCT GCC432Asp Gly Gln Ala Ser Arg Leu Pro Asp Ala Leu Thr Ser Ala Ser Ala130 135 140GCC AGA GTG TCC TCC TCT GGC CCC ACC AGC CCA GTG GTC GCG CAG CTT480Ala Arg Val Ser Ser Ser Gly Pro Thr Ser Pro Val Val Ala Gln Leu145 150 155 160CTG AGG CCA GCA TGC ATG GCC CTG ACC AGG GAC AAC CAC CAC TTC TAT528Leu Arg Pro Ala Cys Mer Ala Leu Thr Arg Asp Asn His His Phe Tyr165 170 175AAC CGG AAC TTC TGC CAG GGA ACC CAC GGC CGA ATA GCC GTG AGC CGG576Asn Arg Asn Phe Cys Gln Gly Thr His Gly Arg Ile Ala Val Ser Arg180 185 190
AAT CCT GCA CGG TGC CAC CTC CAC ACA CAC CTA ACA TAT GCC TGC CTG 624Asn Pro Ala Arg Cys His Leu His Thr His Leu Thr Tyr Ala Cys Leu195 200 205ATC TGACCAACAC ATGCTCGCCA CCCTCACCAC ACACC 662IleASTCAWPGFPGGGGKVGEMRMPCPTMPSWSSTKRRAQWQTGCTTSFGGSWRSAVGAGHSACAWRNATGCLAKPSLRTCGPRSMAAARRCLCWPTRTGSVVSCAPVLLLAQQRLLEDRKDVVVLVILTPDGQASRLPDALTSASAARVSSSGPTSPVVAQLLRPACMALTRDNHHFYNRNFCQGTHGRIAVSRNPARCHLHTHLTYACLI诸如人等灵长类动物的DTLR10的附加序列(SEQ ID NO33和34)；用A表示的第854位核苷酸可以是A或T；并且用C表示的第1171和1172位核苷酸的每个都可以是A、C、G或TCTG CCT GCT GGC ACC CGG CTC CGG AGG CTG GAT GTC AGC TGC AAC AGC 48Leu Pro Ala Gly Thr Arg Leu Arg Arg Leu Asp Val Ser Cys Asn Ser1 5 10 15ATC AGC TTC GTG GCC CCC GGC TTC TTT TCC AAG GCC AAG GAG CTG CGA 96Ile Ser Phe Val Ala Pro Gly Phe Phe Ser Lys Ala Lys Glu Leu Arg20 25 30GAG CTC AAC CTT AGC GCC AAC GCC CTC AAG ACA GTG GAC CAC TCC TGG144Glu Leu Asn Leu Ser Ala Asn Ala Leu Lys Thr Val Asp His Ser Trp35 40 45TTT GGG CCC CTG GCG AGT GCC CTG CAA ATA CTA GAT GTA AGC GCC AAC192Phe Gly Pro Leu Ala Ser Ala Leu Gln Ile Leu Asp Val Ser Ala Asn50 55 60CCT CTG CAC TGC GCC TGT GGG GCG GCC TTT ATG GAC TTC CTG CTG GAG240Pro Leu His Cys Ala Cys Gly Ala Ala Phe Met Asp Phe Leu Leu Glu65 70 75 80GTG CAG GCT GCC GTG CCC GGT CTG CCC AGC CGG GTG AAG TGT GGC AGT288Val Gln Ala Ala Val Pro Gly Leu Pro Ser Arg Val Lys Cys Gly Ser85 90 95CCG GGC CAG CTC CAG GGC CTC AGC ATC TTT GCA CAG GAC CTG CGC CTC336Pro Gly Gln Leu Gln Gly Leu Ser Ile Phe Ala Gln Asp Leu Arg Leu100 105 110TGC CTG GAT GAG GCC CTC TCC TGG GAC TGT TTC GCC CTC TCG CTG CTG384Cys Leu Asp Glu Ala Leu Ser Trp Asp Cys Phe Ala Leu Ser Leu Leu115 120 125GCT GTG GCT CTG GGC CTG GGT GTG CCC ATG CTG CAT CAC CTC TGT GGC432Ala Val Ala Leu Gly Leu Gly Val Pro Met Leu His His Leu Cys Gly130 135 140TGG GAC CTC TGG TAC TGC TTC CAC CTG TGC CTG GCC TGG CTT CCC TGG480Trp Asp Leu Trp Tyr Cys Phe His Leu Cys Leu Ala Trp Leu Pro Trp145 150 155 160
CGG GGG CGG CAA AGT GGG CGA GAT GAG GAT GCC CTG CCC TAC GAT GCC528Arg Gly Arg Gln Ser Gly Arg Asp Glu Asp Ala Leu Pro Tyr Asp Ala165 170 175TTC GTG GTC TTC GAC AAA ACG CAG AGC GCA GTG GCA GAC TGG GTG TAC576Phe Val Val Phe Asp Lys Thr Gln Ser Ala Val Ala Asp Trp Val Tyr180 185 190AAC GAG CTT CGG GGG CAG CTG GAG GAG TGC CGT GGG CGC TGG GCA CTC624Asn Glu Leu Arg Gly Gln Leu Glu Glu Cys Arg Gly Arg Trp Ala Leu195 200 205CGC CTG TGC CTG GAG GAA CGC GAC TGG CTG CCT GGC AAA ACC CTC TTT672Arg Leu Cys Leu Glu Glu Arg Asp Trp Leu Pro Gly Lys Thr Leu Phe210 215 220GAG AAC CTG TGG GCC TCG GTC TAT GGC AGC CGC AAG ACG CTG TTT GTG720Glu Asn Leu Trp Ala Ser Val Tyr Gly Ser Arg Lys Thr Leu Phe Val225 230 235 240CTG GCC CAC ACG GAC CGG GTC AGT GGT CTC TTG CGC GCC AGC TTC CTG768Leu Ala His Thr Asp Arg Val Ser Gly Leu Leu Arg Ala Ser Phe Leu245 250 255CTG GCC CAG CAG CGC CTG CTG GAG GAC CGC AAG GAC GTC GTG GTG CTG816Leu Ala Gln Gln Arg Leu Leu Glu Asp Arg Lys Asp Val Val Val Leu260 265 270GTG ATC CTG AGC CCT GAC GGC CGC CGC TCC CGC TAC GAG CGG CTG CGC864Val Ile Leu Ser Pro Asp Gly Arg Arg Ser Arg Tyr Glu Arg Leu Arg275 280 285CAG CGC CTC TGC CGC CAG AGT GTC CTC CTC TGG CCC CAC CAG CCC AGT912Gln Arg Leu Cys Arg Gln Ser Val Leu Leu Trp Pro His Gln Pro Ser290 295 300GGT CAG CGC AGC TTC TGG GCC CAG CTG GGC ATG GCC CTG ACC AGG GAC960Gly Gln Arg Ser Phe Trp Ala Gln Leu Gly Met Ala Leu Thr Arg Asp305 310 315 320AAC CAC CAC TTC TAT AAC CGG AAC TTC TGC CAG GGA CCC ACG GCC GAA 1008Asn His His Phe Tyr Asn Arg Asn Phe Cys Gln Gly Pro Thr Ala Glu325 330 335TAGCCGTGAG CCGGAATCCT GCACGGTGCC ACCTCCACAC TCACCTCACC TCTGCCTGCC 1068TGGTCTGACC CTCCCCTGCT CGCCTCCCTC ACCCCACACC TGACACAGAG CAGGCACTCA 1128ATAAATGCTA CCGAAGGCTA AAAAAAAAAA AAAAAAAAAA AACCA 1173
LPAGTRLRRLDVSCNSISFVAPGFFSKAKELRELNLSANALKTVDHSWFGPLASALQILDVSANPLHCACGAAFMDFLLEVQAAVPGLPSRVKCGSPGQLQGLSIFAQDLRLCLDEALSWDCFALSLLAVALGLGVPMLHHLCGWDLWYCFHLCLAWLPWRGRQSGRDEDALPYDAFVVFDKTQSAVADWVYNELRGQLEECRGRWALRLCLEERDWLPGKTLFENLWASVYGSRKTLFVLAHTDRVSGLLRASFLLAQQRLLEDRKDVVVLVILSPDGRRSRY.RLRQRLCRQSVLLWPHQPSGQRSFWAQLGMALTRDNHHFYNRNFCQGPTAE诸如人等灵长类动物的DTLRl0的其他序列(SEQ ID NO42和43)atg ccc atg aag tgg agt ggg tgg agg tgg agc tgg ggg ccg gcc act48Met Pro Met Lys Trp Ser Gly Trp Arg Trp Ser Trp Gly Pro Ala Thr-45 -40 -35cac aca gcc ctc cca ccc cca cag ggt ttc tgc cgc agc gcc ctg cac96His Thr Ala Leu Pro Pro Pro Gln Gly Phe Cys Arg Ser Ala Leu His-30 -25 -20ccg ctg tct ctc ctg gtg cag gcc atc atg ctg gcc atg acc ctg gcc 144Pro Leu Ser Leu Leu Val Gln Ala Ile Met Leu Ala Met Thr Leu Ala-15 -10 -5 -1ctg ggt acc ttg cct gcc ttc cta ccc tgt gag ctc cag ccc cac ggc 192Leu Gly Thr Leu Pro Ala Phe Leu Pro Cys Glu Leu Gln Pro His Gly1 5 10 15ctg gtg aac tgc aac tgg ctg ttc ctg aag tct gtg ccc cac ttc tcc 240Leu Val Asn Cys Asn Trp Leu Phe Leu Lys Ser Val Pro His Phe Ser20 25 30atg gca gca ccc cgt ggc aat gtc acc agc ctt tcc ttg tcc tcc aac 288Met Ala Ala Pro Arg Gly Asn Val Thr Ser Leu Ser Leu Ser Ser Asn35 40 45cgc atc cac cac ctc cat gat tct gac ttt gcc cac ctg ccc agc ctg 336Arg Ile His His Leu His Asp Ser Asp Phe Ala His Leu Pro Ser Leu50 55 60cgg cat ctc aac ctc aag tgg aac tgc ccg ccg gtt ggc ctc agc ccc 384Arg His Leu Asn Leu Lys Trp Asn Cys Pro Pro Val Gly Leu Ser Pro65 70 75 80atg cac ttc ccc tgc cac atg acc atc gag ccc agc acc ttc ttg gct 432Met His Phe Pro Cys His Met Thr Ile Glu Pro Ser Thr Phe Leu Ala85 90 95gtg ccc acc ctg gaa gag cta aac ctg agc tac aac aac atc atg act 480Val Pro Thr Leu Glu Glu Leu Asn Leu Ser Tyr Asn Asn Ile Met Thr100 105 110gtg cct gcg ctg ccc aaa tcc ctc ata tcc ctg tcc ctc agc cat acc 528Val Pro Ala Leu Pro Lys Ser Leu Ile Ser Leu Ser Leu Ser His Thr115 120 125aac atc ctg atg cta gac tct gcc agc ctc gcc ggc ctg cat gcc ctg 576Asn Ile Leu Met Leu Asp Ser Ala Ser Leu Ala Gly Leu His Ala Leu130 135 140
cgc ttc cta ttc atg gac ggc aac tgt tat tac aag aac ccc tgc agg 624Arg Phe Leu Phe Met Asp Gly Asn Cys Tyr Tyr Lys Asn Pro Cys Arg145 150 155 160cag gca ctg gag gtg gcc ccg ggt gcc ctc ctt ggc ctg ggc aac ctc 672Gln Ala Leu Glu Val Ala Pro Gly Ala Leu Leu Gly Leu Gly Asn Leu165 170 175acc cac ctg tca ctc aag tac aac aac ctc act gtg gtg ccc cgc aac 720Thr His Leu Ser Leu Lys Tyr Asn Asn Leu Thr Val Val Pro Arg Asn180 185 190ctg cct tcc agc ctg gag tat ctg ctg ttg tcc tac aac cgc atc gtc 768Leu Pro Ser Ser Leu Glu Tyr Leu Leu Leu Ser Tyr Asn Arg Ile Val195 200 205aaa ctg gcg cct gag gac ctg gcc aat ctg acc gcc ctg cgt gtg ctc 816Lys Leu Ala Pro Glu Asp Leu Ala Asn Leu Thr Ala Leu Arg Val Leu210 215 220gat gtg ggc gga aat tgc cgc cgc tgc gac cac gct ccc aac ccc tgc 864Asp Val Gly Gly Asn Cys Arg Arg Cys Asp His Ala Pro Asn Pro Cys225 230 235 240atg gag tgc cct cgt cac ttc ccc cag cta cat ccc gat acc ttc agc 912Met Glu Cys Pro Arg His Phe Pro Gln Leu His Pro Asp Thr Phe Ser245 250 255cac ctg agc cgt ctt gaa ggc ctg gtg ttg aag gac agt tct ctc tcc 960His Leu Ser Arg Leu Glu Gly Leu Val Leu Lys Asp Ser Ser Leu Ser260 265 270tgg ctg aat gcc agt tgg ttc cgt ggg ctg gga aac ctc cga gtg ctg 1008Trp Leu Asn Ala Ser Trp Phe Arg Gly Leu Gly Asn Leu Arg Val Leu275 280 285gac ctg agt gag aac ttc ctc tac aaa tgc atc act aaa acc aag gcc 1056Asp Leu Ser Glu Asn Phe Leu Tyr Lys Cys Ile Thr Lys Thr Lys Ala290 295 300ttc cag ggc cta aca cag ctg cgc aag ctt aac ctg tcc ttc aat tac 1104Phe Gln Gly Leu Thr Gln Leu Arg Lys Leu Asn Leu Ser Phe Asn Tyr305 310 315 320caa aag agg gtg tcc ttt gcc cac ctg tct ctg gcc cct tcc ttc ggg 1152Gln Lys Arg Val Ser Phe Ala His Leu Ser Leu Ala Pro Ser Phe Gly325 330 335agc ctg gtc gcc ctg aag gag ctg gac atg cac ggc atc ttc ttc cgc 1200Ser Leu Val Ala Leu Lys Glu Leu Asp Met His Gly Ile Phe Phe Arg340 345 350tca ctc gat gag acc acg ctc cgg cca ctg gcc cgc ctg ccc atg ctc 1248Ser Leu Asp Glu Thr Thr Leu Arg Pro Leu Ala Arg Leu Pro Met Leu355 360 365
cag act ctg cgt ctg cag atg aac ttc atc aac cag gcc cag ctc ggc1296Gln Thr Leu Arg Leu Gln Met Asn Phe Ile Asn Gln Ala Gln Leu Gly370 375 380atc ttc agg gcc ttc cct ggc ctg cgc tac gtg gac ctg tcg gac aac1344Ile Phe Arg Ala Phc Pro Gly Leu Arg Tyr Val Asp Leu Ser Asp Asn385 390 395 400cgc atc agc gga gct tcg gag ctg aca gcc acc atg ggg gag gca gat1392Arg Ile Ser Gly Ala Ser Glu Leu Thr Ala Thr Met Gly Glu Ala Asp405 410 415gga ggg gag aag gtc tgg ctg cag cct ggg gac ctt gct ccg gcc cca1440Gly Gly Glu Lys Val Trp Leu Gln Pro Gly Asp Leu Ala Pro Ala Pro420 425 430gtg gac act ccc agc tct gaa gac ttc agg ccc aac tgc agc acc ctc1488Val Asp Thr Pro Ser Ser Glu Asp Phe Arg Pro Asn Cys Ser Thr Leu435 440 445aac ttc acc ttg gat ctg tca cgg aac aac ctg gtg acc gtg cag ccg1536Asn Phe Thr Leu Asp Leu Ser Arg Asn Asn Leu Val Thr Val Gln Pro450 455 460gag atg ttt gcc cag ctc tcg cac ctg cag tgc ctg cgc ctg agc cac1584Glu Met Phe Ala Gln Leu Ser His Leu Gln Cys Leu Arg Leu Ser His465 470 475 480aac tgc atc tcg cag gca gtc aat ggc tcc cag ttc ctg ccg ctg acc1632Asn Cys Ile Ser Gln Ala Val Asn Gly Ser Gln Phe Leu Pro Leu Thr485 490 495ggt ctg cag gtg cta gac ctg tcc cac aat aag ctg gac ctc tac cac1680Gly Leu Gln Val Leu Asp Leu Ser His Asn Lys Leu Asp Leu Tyr His500 505 510gag cac tca ttc acg gag cta cca cga ctg gag gcc ctg gac ctc agc1728Glu His Ser Phe Thr Glu Leu Pro Arg Leu Glu Ala Leu Asp Leu Ser515 520 525tac aac agc cag ccc ttt ggc atg cag ggc gtg ggc cac aac ttc agc1776Tyr Asn Ser Gln Pro Phe Gly Met Gln Gly Val Gly His Asn Phe Ser530 535 540ttc gtg gct cac ctg cgc acc ctg cgc cac ctc agc ctg gcc cac aac1824Phe Val Ala His Leu Arg Thr Leu Arg His Leu Ser Leu Ala His Asn545 550 555 560aac atc cac agc caa gtg tcc cag cag ctc tgc agt acg tcg ctg cgg1872Asn Ile His Ser Gln Val Ser Gln Gln Leu Cys Ser Thr Ser Leu Arg565 570 575gcc ctg gac ttc agc ggc aat gca ctg ggc cat atg tgg gcc gag gga1920Ala Leu Asp Phe Ser Gly Asn Ala Leu Gly His Met Trp Ala Glu Gly580 585 590
gac ctc tat ctg cac ttc ttc caa ggc ctg agc ggt ttg atc tgg ctg 1968Asp Leu Tyr Leu His Phe Phe Gln Gly Leu Ser Gly Leu Ile Trp Leu595 600 605gac ttg tcc cag aac cgc ctg cac acc ctc ctg ccc caa acc ctg cgc 2016Asp Leu Ser Gln Asn Arg Leu His Thr Leu Leu Pro Gln Thr Leu Arg610 615 620aac ctc ccc aag agc cta cag gtg ctg cgt ctc cgt gac aat tac ctg 2064Asn Leu Pro Lys Ser Leu Gln Val Leu Arg Leu Arg Asp Asn Tyr Leu625 630 635 640gcc ttc ttt aag tgg tgg agc ctc cac ttc ctg ccc aaa ctg gaa gtc 2112Ala Phe Phe Lys Trp Trp Ser Leu His Phe Leu Pro Lys Leu Glu Val645 650 655ctc gac ctg gca gga aac cag ctg aag gcc ctg acc aat ggc agc ctg 2160Leu Asp Leu Ala Gly Asn Gln Leu Lys Ala Leu Thr Asn Gly Ser Leu660 665 670cct gct ggc acc cgg ctc cgg agg ctg gat gtc agc tgc aac agc atc 2208Pro Ala Gly Thr Arg Leu Arg Arg Leu Asp Val Ser Cys Asn Ser Ile675 680 685agc ttc gtg gcc ccc ggc ttc ttt tcc aag gcc aag gag ctg cga gag 2256Ser Phe Val Ala Pro Gly Phe Phe Ser Lys Ala Lys Glu Leu Arg Glu690 695 700ctc aac ctt agc gcc aac gcc ctc aag aca gtg gac cac tcc tgg ttt 2304Leu Asn Leu Ser Ala Asn Ala Leu Lys Thr Val Asp His Ser Trp Phe705 710 715 720ggg ccc ctg gcg agt gcc ctg caa ata cta gat gta agc gcc aac cct 2352Gly Pro Leu Ala Ser Ala Leu Gln Ile Leu Asp Val Ser Ala Asn Pro725 730 735ctg cac tgc gcc tgt ggg gcg gcc ttt atg gac ttc ctg ctg gag gtg 2400Leu His Cys Ala Cys Gly Ala Ala Phe Met Asp Phe Leu Leu Glu Val740 745 750cag gct gcc gtg ccc ggt ctg ccc agc cgg gtg aag tgt ggc agt ccg 2448Gln Ala Ala Val Pro Gly Leu Pro Ser Arg Val Lys Cys Gly Ser Pro755 760 765ggc cag ctc cag ggc ctc agc atc ttt gca cag gac ctg cgc ctc tgc 2496Gly Gln Leu Gln Gly Leu Ser Ile Phe Ala Gln Asp Leu Arg Leu Cys770 775 780ctg gat gag gcc ctc tcc tgg gac tgt ttc gcc ctc tcg ctg ctg gct 2544Leu Asp Glu Ala Leu Ser Trp Asp Cys Phe Ala Leu Ser Leu Leu Ala785 790 795 800gtg gct ctg ggc ctg ggt gtg ccc atg ctg cat cac ctc tgt ggc tgg 2592Val Ala Leu Gly Leu Gly Val Pro Met Leu His His Leu Cys Gly Trp805 810 815
gac ctc tgg tac tgc ttc cac ctg tgc ctg gcc tgg ctt ccc tgg cgg2640Asp Leu Trp Tyr Cys Phe His Leu Cys Leu Ala Trp Leu Pro Trp Arg820 825 830ggg cgg caa agt ggg cga gat gag gat gcc ctg ccc tac gat gcc ttc2688Gly Arg Gln Ser Gly Arg Asp Glu Asp Ala Leu Pro Tyr Asp Ala Phe835 840 845gtg gtc ttc gac aaa acg cag agc gca gtg gca gac tgg gtg tac aac2736Val Val Phe Asp Lys Thr Gln Ser Ala Val Ala Asp Trp Val Tyr Asn850 855 860gag ctt cgg ggg cag ctg gag gag tgc cgt ggg cgc tgg gca ctc cgc2784Glu Leu Arg Gly Gln Leu Glu Glu Cys Arg Gly Arg Trp Ala Leu Arg865 870 875 880ctg tgc ctg gag gaa cgc gac tgg ctg cct ggc aaa acc ctc ttt gag2832Leu Cys Leu Glu Glu Arg Asp Trp Leu Pro Gly Lys Thr Leu Phe Glu885 890 895aac ctg tgg gcc tcg gtc tat ggc agc cgc aag acg ctg ttt gtg ctg2880Asn Leu Trp Ala Ser Val Tyr Gly Ser Arg Lys Thr Leu Phe Val Leu900 905 910gcc cac acg gac cgg gtc agt ggt ctc ttg cgc gcc agc ttc ctg ctg2928Ala His Thr Asp Arg Val Ser Gly Leu Leu Arg Ala Ser Phe Leu Leu915 920 925gcc cag cag cgc ctg ctg gag gac cgc aag gac gtc gtg gtg ctg gtg2976Ala Gln Gln Arg Leu Leu Glu Asp Arg Lys Asp Val Val Val Leu Val930 935 940atc ctg agc cct gac ggc cgc cgc tcc cgc tat gtg cgg ctg cgc cag3024Ile Leu Ser Pro Asp Gly Arg Arg Ser Arg Tyr Val Arg Leu Arg Gln945950 955 960cgc ctc tgc cgc cag agt gtc ctc ctc tgg ccc cac cag ccc agt ggt3072Arg Leu Cys Arg Gln Ser Val Leu Leu Trp Pro His Gln Pro Ser Gly965 970 975cag cgc agc ttc tgg gcc cag ctg ggc atg gcc ctg acc agg gac aac3120Gln Arg Ser Phe Trp Ala Gln Leu Gly Met Ala Leu Thr Arg Asp Asn980 985 990cac cac ttc tat aac cgg aac ttc tgc cag gga ccc acg gcc gaa tag3168His His Phe Tyr Asn Arg Asn Phe Cys Gln Gly Pro Thr Ala Glu99510001005
MPMKWSGWRWSWGPATHTALPPPQGFCRSALHPLSLLVQAIMLAMTLALGTLPAFLPCELQPHGLVNCNWLFLKSVPHFSMAAPRGNVTSLSLSSNRIHHLHDSDFAHLPSLRHLNLKWNCPPVGLSPMHFPCHMTIEPSTFLAVPTLEELNLSYNNIMTVPALPKSLISLSLSHTNILMLDSASLAGLHALRFLFMDGNCYYKNPCRQALEVAPGALLGLGNLTHLSLKYNNLTVVPRNLPSSLEYLLLSYNRIVKLAPEDLANLTALRVLDVGGNCRRCDHAPNPCMECPRHFPQLHPDTFSHLSRLEGLVLKDSSLSWLNASWFRGLGNLRVLDLSENFLYKCITKTKAFQGLTQLRKLNLSFNYQKRVSFAHLSLAPSFGSLVALKELDMHGIFFRSLDETTLRPLARLPMLQTLRLQMNFINQAQLGIFRAFPGLRYVDLSDNRISGASELTATMGEADGGEKVWLQPGDLAPAPVDTPSSEDFRPNCSTLNFTLDLSRNNLVTVQPEMFAQLSHLQCLRLSHNCISQAVNGSQFLPLTGLQVLDLSHNKLDLYHEHSFTELPRLEALDLSYNSQPFGMQGVGHNFSFVAHLRTLRHLSLAHNNIHSQVSQQLCSTSLRALDFSGNALGHMWAEGDLYLHFFQGLSGLIWLDLSQNRLHTLLPQTLRNLPKSLQVLRLRDNYLAFFKWWSLHFLPKLEVLDLAGNQLKALTNGSLPAGTRLRRLDVSCNSISFVAPGFFSKAKELRELNLSANALKTVDHSWFGPLASALQILDVSANPLHCACGAAFMDFLLEVQAAVPGLPSRVKCGSPGQLQGLSIFAQDLRLCLDEALSWDCFALSLLAVALGLGVPMLHHLCGWDLWYCFHLCLAWLPWRGRQSGRDEDALPYDAFVVFDKTQSAVADWVYNELRGQLEECRGRWALRLCLEERDWLPGKTLFENLWASVYGSRKTLFVLAHTDRVSGLLRASFLLAQQRLLEDRKDVVVLVILSPDGRRSRYVRLRQRLCRQSVLLWPHQPSGQRSFWAQLGMALTRDNHHFYNRNFCQGPTAE诸如小鼠等啮齿动物的DTLR10的部分核苷酸序列(SEQ ID NO35)TGGCCCACAC GGACCGCGTC AGTGGCCTCC TGCGCACCAG CTTCCTGCTG GCTCAGCAGC 60GCCTGTTGGA AGACCGCAAG GACGTGGTGG TGTTGGTGAT CCTGCGTCCG GATGCCCCAC 120CGTCCCGCTA TGTGCGACTG CGCCAGCGTC TCTGCCGCCA GAGTGTGCTC TTCTGGCCCC 180AGCGACCCAA CGGGCAGGGG GGCTTCTGGG CCCAGCTGAG TACAGCCCTG ACTAGGGACA 240ACCGCCACTT CTATAACCAG AACTTCTGCC GGGGACCTAC AGCAGAATAG CTCAGAGCAA 300CAGCTGGAAA CAGCTGCATC TTCATGTCTG GTTCCCGAGT TGCTCTGCCT GCCTTGCTCT 360GTCTTACTAC ACCGCTATTT GGCAAGTGCG CAATATATGC TACCAAGCCA CCAGGCCCAC 420GGAGCAAAGG TTGGCTGTAA AGGGTAGTTT TCTTCCCATG CATCTTTCAG GAGAGTGAAG 480ATAGACACCA AACCCAC497诸如小鼠等啮齿动物的DTLR10的其他序列(SEQ ID NO44和45)aac ctg tcc ttc aat tac cgc aag aag gta tcc ttt gcc cgc ctc cac 48Asn Leu Ser Phe Asn Tyr Arg Lys Lys Val Ser Phe Ala Arg Leu His1 5 10 15ctg gca agt tcc ttt aag aac ctg gtg tca ctg cag gag ctg aac atg 96Leu Ala Ser Ser Phe Lys Asn Leu Val Ser Leu Gln Glu Leu Asn Met20 25 30aac ggc atc ttc ttc cgc ttg ctc aac aag tac acg ctc aga tgg ctg 144Asn Gly Ile Phe Phe Arg Leu Leu Asn Lys Tyr Thr Leu Arg Trp Leu35 40 45gcc gat ctg ccc aaa ctc cac act ctg cat ctt caa atg aac ttc atc 192Ala Asp Leu Pro Lys Leu His Thr Leu His Leu Gln Met Asn Phe Ile50 55 60
aac cag gca cag ctc agc atc ttt ggt acc ttc cga gcc ctt cgc ttt240Asn Gln Ala Gln Leu Ser Ile Phe Gly Thr Phe Arg Ala Leu Arg Phe65 70 75 80gtg gac ttg tca gac aat cgc atc agt ggg cct tca acg ctg tca gaa288Val Asp Leu Ser Asp Asn Arg Ile Ser Gly Pro Ser Thr Leu Ser Glu85 90 95gcc acc cct gaa gag gca gat gat gca gag cag gag gag ctg ttg tct336Ala Thr Pro Glu Glu Ala Asp Asp Ala Glu Gln Glu Glu Leu Leu Ser100 105 110gcg gat cct cac cca gct ccg ctg agc acc cct gct tct aag aac ttc384Ala Asp Pro His Pro Ala Pro Leu Ser Thr Pro Ala Ser Lys Asn Phe115 120 125atg gac agg tgt aag aac ttc aag ttc aac atg gac ctg tct cgg aac432Met Asp Arg Cys Lys Asn Phe Lys Phe Asn Met Asp Leu Ser Arg Asn130 135 140aac ctg gtg act atc aca gca gag atg ttt gta aat ctc tca cgc ctc480Asn Leu Val Thr Ile Thr Ala Glu Met Phe Val Asn Leu Ser Arg Leu145 150 155 160cag tgt ctt agc ctg agc cac aac tca att gca cag gct gtc aat ggc528Gln Cys Leu Ser Leu Ser His Asn Ser Ile Ala Gln Ala Val Asn Gly165 170 175tct cag ttc ctg ccg ctg acc ggt ctg cag gtg cta gac ctg tcc cac576Ser Gln Phe Leu Pro Leu Thr Gly Leu Gln Val Leu Asp Leu Ser His180 185 190aat aag ctg gac ctc tac cac gag cac tca ttc acg gag cta cca cga624Asn Lys Leu Asp Leu Tyr His Glu His Ser Phe Thr Glu Leu Pro Arg195 200 205ctg gag gcc ctg gac ctc agc tac aac agc cag ccc ttt agc atg aag672Leu Glu Ala Leu Asp Leu Ser Tyr Asn Ser Gln Pro Phe Ser Met Lys210 215 220ggt ata ggc cac aat ttc agt ttt gtg acc cat ctg tcc atg cta cag720Gly Ile Gly His Asn Phe Ser Phe Val Thr His Leu Ser Met Leu Gln225 230 235 240agc ctt agc ctg gca cac aat gac att cat acc cgt gtg tcc tca cat768Ser Leu Ser Leu Ala His Asn Asp Ile His Thr Arg Val Ser Ser His245 250 255ctc aac agc aac tca gtg agg ttt ctt gac ttc agc ggc aac ggt atg816Leu Asn Ser Asn Ser Val Arg Phe Leu Asp Phe Ser Gly Asn Gly Met260 265 270ggc cgc atg tgg gat gag ggg ggc ctt tat ctc cat ttc ttc caa ggc864Gly Arg Met Trp Asp Glu Gly Gly Leu Tyr Leu His Phe Phe Gln Gly275 280 285
ctg agt ggc gtg ctg aag ctg gac ctg tct caa aat aac ctg cat atc912Leu Ser Gly Val Leu Lys Leu Asp Leu Ser Gln Asn Asn Leu His Ile290 295 300ctc cgg ccc cag aac ctt gac aac ctc ccc aag agc ctg aag ctg ctg960Leu Arg Pro Gln Asn Leu Asp Asn Leu Pro Lys Ser Leu Lys Leu Leu305 310 315 320agc ctc cga gac aac tac cta tct ttc ttt aac tgg acc agt ctg tcc 1008Ser Leu Arg Asp Asn Tyr Leu Ser Phe Phe Asn Trp Thr Ser Leu Ser325 330 335ttc cta ccc aac ctg gaa gtc cta gac ctg gca ggc aac cag cta aag 1056Phe Leu Pro Asn Leu Glu Val Leu Asp Leu Ala Gly Asn Gln Leu Lys340 345 350gcc ctg acc aat ggc acc ctg cct aat ggc acc ctc ctc cag aaa ctc 1104Ala Leu Thr Asn Gly Thr Leu Pro Asn Gly Thr Leu Leu Gln Lys Leu355 360 365gat gtc agt agc aac agt atc gtc tct gtg gcc ccc ggc ttc ttt tcc 1152Asp Val Ser Ser Asn Ser Ile Val Ser Val Ala Pro Gly Phe Phe Ser370 375 380aag gcc aag gag ctg cga gag ctc aac ctt agc gcc aac gcc ctc aag 1200Lys Ala Lys Glu Leu Arg Glu Leu Asn Leu Ser Ala Asn Ala Leu Lys385 390 395 400aca gtg gac cac tcc tgg ttt ggg ccc att gtg atg aac ctg aca gtt 1248Thr Val Asp His Ser Trp Phe Gly Pro Ile Val Met Asn Leu Thr Val405 410 415cta gac gtg aga agc aac cct ctg cac tgt gcc tgt ggg gca gcc ttc 1296Leu Asp Val Arg Ser Asn Pro Leu His Cys Ala Cys Gly Ala Ala Phe420 425 430gta gac tta ctg ttg gag gtg cag acc aag gtg cct ggc ctg gct aat 1344Val Asp Leu Leu Leu Glu Val Gln Thr Lys Val Pro Gly Leu Ala Asn435 440 445ggt gtg aag tgt ggc agc ccc ggc cag ctg cag ggc cgt agc atc ttc 1392Gly Val Lys Cys Gly Ser Pro Gly Gln Leu Gln Gly Arg Ser Ile Phe450 455 460gcg cag gac ctg cgg ctg tgc ctg gat gag gtc ctc tct tgg gac tgc 1440Ala Gln Asp Leu Arg Leu Cys Leu Asp Glu Val Leu Ser Trp Asp Cys465 470 475 480ttt ggc ctt tca ctc ttg gct gtg gcc gtg ggc atg gtg gtg cct ata 1488Phe Gly Leu Set Leu Leu Ala Val Ala Val Gly Met Val Val Pro Ile485 490 495ctg cac cat ctc tgc ggc tgg gac gtc tgg tac tgt ttt cat ctg tgc 1536Leu His His Leu Cys Gly Trp Asp Val Trp Tyr Cys Phe His Leu Cys500 505 510
ctg gca tgg cta cct ttg cta gcc cgc agc cga cgc agc gcc caa act1584Leu Ala Trp Leu Pro Leu Leu Ala Arg Ser Arg Arg Ser Ala Gln Thr515 520 525ctc cct tat gat gcc ttc gtg gtg ttc gat aag gca cag agc gca gtt1632Leu Pro Tyr Asp Ala Phe Val Val Phe Asp Lys Ala Gln Ser Ala Val530 535 540gcc gac tgg gtg tat aac gag ctg cgg gtg cgg ctg gag gag cgg cgc1680Ala Asp Trp Val Tyr Asn Glu Leu Arg Val Arg Leu Glu Glu Arg Arg545 550 555 560ggc cgc tgg gca ctc cgc ctg tgc ctg gag gac cga gat tgg ctg cct1728Gly Arg Trp Ala Leu Arg Leu Cys Leu Glu Asp Arg Asp Trp Leu Pro565 570 575ggc cag acg ctc ttc gag aac ctc tgg gct tcc atc tat ggg agc cgc1776Gly Gln Thr Leu Phe Glu Asn Leu Trp Ala Ser Ile Tyr Gly Ser Arg580 585 590aag act cta ttt gtg ctg gcc cac acg gac cgc gtc agt ggc ctc ctg1824Lys Thr Leu Phe Val Leu Ala His Thr Asp Arg Val Ser Gly Leu Leu595 600 605cgc acc agc ttc ctg ctg gct cag cag cgc ctg ttg gaa gac cgc aag1872Arg Thr Ser Phe Leu Leu Ala Gln Gln Arg Leu Leu Glu Asp Arg Lys610 615 620gac gtg gtg gtg ttg gtg atc ctg cgt ccg gat gcc cac cgc tcc cgc1920Asp Val Val Val Leu Val Ile Leu Arg Pro Asp Ala His Arg Ser Arg625 630 635 640tat gtg cga ctg cgc cag cgt ctc tgc cgc cag agt gtg ctc ttc tgg1968Tyr Val Arg Leu Arg Gln Arg Leu Cys Arg Gln Ser Val Leu Phe Trp645 650 655ccc cag cag ccc aac ggg cag ggg ggc ttc tgg gcc cag ctg agt aca2016Pro Gln Gln Pro Asn Gly Gln Gly Gly Phe Trp Ala Gln Leu Ser Thr660 665 670gcc ctg act agg gac aac cgc cac ttc tat aac cag aac ttc tgc cgg2064Ala Leu Thr Arg Asp Asn Arg His Phe Tyr Asn Gln Asn Phe Cys Arg675 680 685gga cct aca gca gaa tagctcagag caacagctgg aaacagctgc atcttcatgt2119Gly Pro Thr Ala Glu690ctggttcccg agttgctctg cctgccttgc tctgtcttac tacaccgcta tttggcaagt 2179gcgcaatata tgctaccaag ccaccaggcc cacggagcaa aggttggctg taaagggtag 2239ttttcttccc atgcatcttt caggagagtg aagatagaca ccaaacccac 2289
NLSFNYRKKVSFARLHLASSFKNLVSLQELNMNGIFFRLLNKYTLRWLADLPKLHTLHLQMNFINQAQLSIFGTFRALRFVDLSDNRISGPSTLSEATPEEADDAEQEELLSADPHPAPLSTPASKNFMDRCKNFKFNMDLSRNNLVTITAEMFVNLSRLQCLSLSHNSIAQAVNGSQFLPLTGLQVLDLSHNKLDLYHEHSFTELPRLEALDLSYNSQPFSMKGIGHNFSFVTHLSMLQSLSLAHNDIHTRVSSHLNSNSVRFLDFSGNGMGRMWDEGGLYLHFFQGLSGVLKLDLSQNNLHILRPQNLDNLPKSLKLLSLRDNYLSFFNWTSLSFLPNLEVLDLAGNQLKALTNGTLPNGTLLQKLDVSSNSIVSVAPGFFSKAKELRELNLSANALKTVDHSWFGPIVMNLTVLDVRSNPLHCACGAAFVDLLLEVQTKVPGLANGVKCGSPGQLQGRSIFAQDLRLCLDEVLSWDCFGLSLLAVAVGMVVPILHHLCGWDVWYCFHLCLAWLPLLARSRRSAQTLPYDAFVVFDKAQSAVADWVYNELRVRLEERRGRWALRLCLEDRDWLPGQTLFENLWASIYGSRKTLFVLAHTDRVSGLLRTSFLLAQQRLLEDRKDVVVLVILRPDAHRSRYVRLRQRLCRQSVLFWPQQPNGQGGFWAQLSTALTRDNRHFYNQNFCRGPTAE
表11人DTLRs胞内结构域的比较。DTLR1为SEQ ID NO2；DTLR2为SEQ ID NO4；DTLR3为SEQ ID NO6；DTLR4为SEQ ID NO8；DTLR5为SEQ ID NO10；DTLR6为SEQ ID NO12。在DTLRs中特别重要并且保守的残基，如特征性残基，对应于SEQ ID NO18的tyr10-tyr13残基；trp26残基；cys46残基；trp52残基；pro54-gly55残基；ser69残基；lys71残基；trp134-pro135残基；以及phe144-trp145残基。
DTLR1 QRNLQFHAFISYSGHD---SFWVKNELLPNLEKEG-----MQICLHERNFDTLR9 KENLQFHAFISYSEHD---SAWVKSELVPYLEKED-----IQICLHERNFDTLR8 ------------------------NELIPNLEKEDGS---ILICLYESYFDTLR2 SRNICYDAFVSYSERD---AYWVENLMVQELENFNPP---FKLCLHKRDFDTLR6 SPDCCYDAFIVYDTKDPAVTEWVLAELVAKLEDPREK--HFNLCLEERDWDTLR7 TSQTFYDAYISYDTKDASVTDWVINELRYHLEESRDK--NVLLCLEERDWDTLR10 EDALPYDAFVVFDKTXSAVADWVYNELRGQLEECRGRW-ALRLCLEERDWDTLR4 RGENIYDAFVIYSSQD---EDWVRNELVKNLEEGVPP---FQLCLHYRDFDTLR5 PDMYKYDAYLCFSSKD---FTWVQNALLKHLDTQYSDQNRFNLCFEERDFDTLR3 TEQFEYAAYIIHAYKD---KDWVWEHFSSMEKEDQS----LKFCLEERDF:.. :*::
DTLR1 VPGKSIVENIITC-IEKSYKSIFVLSPNFVQSEWCH-YELYFAHHNLFHEDTLR9 VPGKSIVENIINC-IEKSYKSIFVLSPNFVQSEWCH-YELYFAHHNLFHEDTLR8 DPGKSISENIVSF-IEKSYKSIFVLSPNFVQNEWCH-YEFYFAHHNLFHEDTLR2 IPGKWIIDNIIDS-IEKSHKTVFVLSENFVKSEWCK-YELDFSHFRLFEEDTLR6 LPGQPVLENLSQS-IQLSKKTVFVMTDKYAKTENFK-IAFYLSHQRLMDEDTLR7 DPGLAIIDNLMQS-INQSKKTVFVLTKKYAKSWNFK-TAFYLXLQRLMGEDTLR10 LPGKTLFENLWAS-VYGSRKTLFVLAHTDRVSGLLR-AIFLLAQQRLLE-DTLR4 IPGVAIAANIIHEGFHKSRKVIVVVSQHFIQSRWCI-FEYEIAQTWQFLSDTLR5 VPGENRIANIQDA-IWNSRKIVCLVSRHFLRDGWCL-EAFSYAQGRCLSDDTLR3 EAGVFELEAIVNS-IKRSRKIIFVITHHLLKDPLCKRFKVHHAVQQAIEQ.* :. * * : ::: :
DTLR1 GSNSLILILLEPIPQYSIPSSYHKLKSLMARRTYLEWPKEKSKRGLFWANDTLR9 GSNNLILILLEPIPQNSIPNKYHKLKALMTQRTYLQWPKEKSKRGLFWA-DTLR8 NSDHIILILLEPIPFYCIPTRYHKLEALLEKKAYLEWPKDRRKCGLFWANDTLR2 NNDAAILILLEPIEKKAIPQRFCKLRKIMNTKTYLEWPMDEAQREGFWVNDTLR6 KVDVIILIFLEKPFQK---SKFLQLRKRLCGSSVLEWPTNPQAHPYFWQCDTLR7 NMDVIIFILLEPVLQH---SPYLRLRQRICKSSILQWPDNPKAERLFWQTDTLR10 --------------------------------------------------DTLR4 SRAGIIFIVLQKVEKT-LLRQQVELYRLLSRNTYLEWEDSVLGRHIFWRRDTLR5 LNSALIMVVVGSLSQY-QLMKHQSIRGFVQKQQYLRWPEDLQDVGWFLHKDTLR3 NLDSIILVFLEEIPDYKLNHALCLRRGMFKSHCILNWPVQKERIGAFRHKDTLR1 LRAAINIKLTEQAKK--------------------------DTLR9 -----------------------------------------DTLR8 LRAAVNVNVLATREMYELQTFTELNEESRGSTISLMRTDCLDTLR2 LRAAIKS----------------------------------DTLR6 LKNALATDNHVAYSQVFKETV--------------------DTLR7 LXNVVLTENDSRYNNMYVDSIKQY-----------------DTLR10 -----------------------------------------DTLR4 LRKALLDGKSWNPEGTVGTGCNWQEATSI------------DTLR5 LSQQILKKEKEKKKDNNIPLQTVATIS--------------DTLR3 LQVALGSKNSVH-----------------------------
跨膜区约相当于灵长类动物DTLR7 SEQ ID NO37的802-818(791-823)；DTLR8 SEQ ID NO39的559-575(550-586)；DTLR9SEQ ID NO41的553-569(549-582)；DTLR10 SEQ ID NO43的796-810(790-814)；以及DTLR10 SEQ ID NO45的481-497(475-503)。
文中使用的术语DNAX Toll样受体2(DTLR2)是指包含一种具有或含有表2所示氨基酸序列的蛋白或肽段的蛋白质或其实质性片段。类似的关系也适用于DTLR3和表3；DTLR4和表4；DTLR5和表5；DTLR6和表6；DTLR7和表7；DTLR8和表8；DTLR9和表9；以及DTLR10和表10。诸如小鼠等啮齿动物的DTLR11序列是由，例如，EST AA739083提供；DTLR13序列是由EST AI019567提供；DTLR14序列是由ESTsAI390330和AA244663提供。
本发明还包括已提供序列的各种DTLR等位体的蛋白变体，如突变型蛋白激动剂或拮抗剂。这些激动剂或拮抗剂的序列差异一般约小于10％，因而常具有1-11倍(fold)取代，如2倍、3倍、5倍、7倍和其他倍取代。此外还包括所述蛋白的等位变体和其他变体，如天然多形性变体。该变体通常能够与其相应生物学受体高亲和力结合，如至少约100nM的亲和力，通常是高于约30nM的亲和力，优选的是高于约10nM的亲和力，更优选的是高于约3nM的亲和力。文中使用的该术语还涉及与所述哺乳动物蛋白相关的天然形式，例如其等位体、多形性变体和代谢变体。
本发明还包括一些具有与表2所示氨基酸序列基本相同的氨基酸序列的蛋白或肽。包括带有较少取代的序列变体，例如，优选的是少于约3-5个取代。类似的特性也适用于表3、4、5、6、7、8、9或10中提供的其他DTLR序列。
实质性多肽“片段”或“肽段”是指至少含有约8个氨基酸的氨基酸残基段，一般是至少10个氨基酸，更一般的是至少12个氨基酸，通常是至少14个氨基酸，更多的是至少16个氨基酸，典型的是至少18个氨基酸，更典型的是至少20个氨基酸，常见的是至少22个氨基酸，更常见的是至少24个氨基酸，优选的是至少26个氨基酸，更优选的是至少28个氨基酸，而在特别优选实施方案中是至少约30个或更多个氨基酸。不同蛋白的片段可以在适当长度的序列段上彼此进行序列比较。
氨基酸序列同源性或序列同一性的测定方法是优化残基匹配，如果必要，还可以在需要的地方引入空位。可参考，例如，Needleham，et a1.，(1970)J.Mol.Biol.48443-453；Sankoff，et al.，(1983)《时间扭曲、信息串编辑和大分子序列比较的理论与实践》第一章，Addison-Wesley，Reading，MA；和IntelliGenetics，Mountain View，CA的软件包；威斯康星大学遗传计算机组(GCG)，Madison，WI；以及NCBI(NIH)；其内容均在此引入作为参考。如果保守取代也被认为是匹配，则测定方法会有所改变。保守取代通常包括在下述分组内部进行的取代甘氨酸，丙氨酸；缬氨酸，异亮氨酸，亮氨酸；天冬氨酸，谷氨酸；天冬酰胺，谷氨酰胺；丝氨酸，苏氨酸；赖氨酸，精氨酸；和苯丙氨酸，酪氨酸。同源氨基酸序列应包括细胞因子序列的天然等位变体和种间变体。典型的同源蛋白或同源肽应该与表2、3、4、5、6、7、8、9或10所示氨基酸序列片段具有50-100％(若引入空位)至60-100％(若包括保守取代)的同源性。同源性测定值应至少约为70％，一般是至少76％，更一般的是至少81％，通常是至少85％，更多的是至少88％，典型的是至少90％，更典型的是至少92％，常见的是至少94％，更常见的是至少95％，优选的是至少96％，更优选的是至少97％，而在特别优选实施方案中是至少98％或更高。同源性程度会随比较片段的长度而有所改变。诸如等位变体等同源蛋白或同源肽应具有表2、3、4、5、6、7、8、9或10所述实施方案的大多数生物活性。通过氨基酸序列比较或核苷酸序列比较而获得的特别引人注意的区域是图2A-2B中标明的区块1-10的内部区域或块内区。
文中使用的术语“生物活性”是指通过相应配体对炎症反应、先天免疫和/或形态发生过程产生的影响，但不局限于此。举例来说，这些受体应能够象IL-1受体那样调节磷酸酶或磷酸化酶的活性，这些活性可通过标准方法来方便地测量。可参考，例如，Hardie，et al.(1995年版)《蛋白激酶手册》第I和第II卷，Academic Press，SanDiego，CA；Hanks，et al.(1991)Meth.Enzymol.20038-62；Hunter，et al.(1992)Cell 70375-388；Lewin(1990)Cell61743-752；Pines，et al.(1991)Cold Spring Harbor Symp.Quant.Biol.56449-463；以及Parker.et al.(1993)Nature363736-738。通过对配体结合的调节，这些受体可表现出非常类似于可调节酶的生物活性。但其周转率更接近于酶，而不是受体复合物。此外，诱导这种酶学活性所需占用的受体数量要少于大多数受体系统，其所需数量更接近于每个细胞数十个受体，相比之下，大多数受体都需要以每个细胞数千个受体的数量来进行触发。这些受体或其部分可作为磷酸标记酶，用来标记常规底物或特定底物。
诸如DTLR等受体的配体、激动剂、拮抗剂和类似物包括那些可以调节对Toll配体样蛋白的特征性细胞应答的分子，当该受体，例如，是一种天然受体或一种抗体时，则还包括那些具有配体-受体相互作用中的其他标准的结合竞争结构特性的分子。这些细胞应答的调节可能是通过不同Toll配体与细胞受体的结合来进行，这些细胞受体与I型或II型IL-1受体有关，但可能截然不同。可参考，例如，Belvinand Anderson(1996)Ann.Rev.Cell Dev.Biol.12393-416；Morisato and Anderson(1995)Ann.Rev.Genetics29371-3991和Hultmark(1994)Nature367116-117。
与此类似，配体可以是能够与所述受体或其类似物结合的天然配体分子，也可以是天然配体的功能类似物。这种功能类似物可以是结构被改变的配体，也可以是完全不相关但其分子形状能够与适当配体结合决定簇相互作用的分子。这些配体可作为激动剂，也可作为拮抗剂。可参考，例如，Goodman，et al.(1990年版)《Goodman &Gilman’s治疗的药学基础》，Pergamon Press，New York。
还可通过受体或抗体以及其他效应剂或配体的分子结构研究来进行合理的药物设计。效应剂可以是调节随配体结合而产生的其他功能的其他蛋白，也可以是通常情况下与受体相互作用的其他蛋白。测定哪些位点与其他特定蛋白相互作用的一种方法是进行物理结构测定，如X-射线晶体学或二维NMR技术。这些测定方法可以提供线索，以了解分子接触区由哪些氨基酸残基构成。有关蛋白质结构测定的详细描述，可参考，例如，Blundell and Johnson(1976)《蛋白质晶体学》Academic Press，New York，其内容在此引入作为参考。
II.活性
Toll样受体蛋白具有多种不同的生物活性，例如在磷酸代谢中能够将其添加至特定底物，也能够将其去除，这些底物一般为蛋白质。其结果通常是对炎症功能、其他先天性免疫应答或形态学作用进行调节。DTLR2、3、4、5、6、7、8、9或10蛋白与其他Toll样受体蛋白同源，但又各自存在结构上的差异。例如，人DTLR2基因编码序列可能与小鼠DTLR2的核苷酸编码序列具有约70％的同一性。在氨基酸水平上可能也具有适当的同一性。
DTLRs的生物活性涉及在底物上添加或去除磷酸基团，其方式通常具有特异性，但有时也以非特异性方式来进行。底物鉴定或酶活性条件的测定可采用标准方法，有关这些方法的描述，可参考，例如，Hardie，et al.(1995年版)《蛋白激酶手册》第I和第II卷，AcademicPress，San Diego，CA；Hanks，et al.1991)Meth.Enzymol.20038-62；Hunter，et al.(1992)Cell 70375-388；Lewin(1990)Cell61743-752；Pines，et al.(1991)Cold Spring Harbor Symp.Quant.Biol.56449-463；以及Parker，et al.(1993)Nature363736-738。
III.核酸本发明涉及分离的核酸或核酸片段的应用，这些核酸或核酸片段可以编码，例如，这些蛋白或其密切相关蛋白，也编码其片段，如编码相应的多肽，优选的是具有生物活性的多肽。此外，本发明还包括分离的或重组的DNA，该DNA编码那些单独具有或整体上具有各DTLRs的特征性序列的蛋白或多肽。该核酸通常能够在适当条件下与表2-10的一种核酸序列段杂交，但优选的是不与表1所示的相应片段杂交。上述生物活性蛋白或多肽可以是全长蛋白，也可以是片段，并且通常含有一段与表2-10所示序列高度同源的氨基酸序列。此外，本发明还包括分离的或重组的核酸或其片段的应用，这些核酸或其片段编码一些含有与DTLR2-10蛋白相同的片段的蛋白。这些分离的核酸可以在5’和3’侧翼区含有相应的调控序列，如启动子、增强子、poly-A附加信号和来源于天然基因的其他调控序列。
“分离的”核酸是指RNA、DNA或混聚物核酸基本上被纯化，例如与源物种中自然伴随天然序列的其他组分相分离，如核糖体、聚合酶和基因组侧翼序列。该术语包括与天然环境脱离的核酸序列，还包括经重组或克隆而与天然成分明显不同的DNA分离物，以及化学合成的类似物或由异源系统生物合成的类似物。基本纯的分子包括完全被纯化或基本上被纯化的分离分子。
分离的核酸通常是一种匀质的分子组合物，但在某些实施方案中也会含有异质成分，优选的是含有少量异质成分。该异质成分通常位于聚合物末端或对特定生物学功能或生物活性不重要的部分。
“重组”核酸一般是按照其产生方法或结构来定义的。根据其产生方法，重组核酸是指，例如，用核酸重组技术获得的产物，这些技术涉及，例如，对核苷酸序列进行人工干预。这种干预通常包括体外操作，但在某些情况下也包括更经典的动物育种技术。作为选择，制备重组核酸的方法也可以是将天然条件下彼此不连续的两种片段融合成一种序列，但重组核酸应排除天然产物，如自然状态下存在的天然突变体。因此，重组核酸包括由任一种非天然载体转化的细胞获得的产物，以及含有经任何寡核苷酸合成方法产生的序列的核酸。这种方法通常是将密码子替换成编码相同氨基酸或保守氨基酸的冗余密码子，同时引入或去除一种限制酶识别位点序列。作为选择，还可利用该方法将具有特定功能的核酸片段相融合，以产生一种不以常见的天然形式存在的单一遗传实体，该遗传实体具有所需的功能组合，如编码一种融合蛋白。这些人工操作一般是针对限制酶识别位点，但也可以设计引入其他位点特异性靶序列，如启动子、DNA复制位点、调节序列、控制序列或其他有用的特性。类似的概念也适用于重组体，如融合蛋白和多肽。此外还包括重复二聚体。此外还特别包括一些合成核酸，根据遗传密码冗余性，这些核酸可以编码与DTLR2-5片段相同的多肽，也编码由多种不同相关分子，如其他IL-1受体家族成员，获得的融合序列。
核酸的“片段”是指至少约17个核苷酸的连续序列段，一般是至少21个核苷酸，更一般的是至少25个核苷酸，普通的是至少30个核苷酸，更普通的是至少35个核苷酸，通常是至少39个核苷酸，更多的是至少45个核苷酸，典型的是至少50个核苷酸，更典型的是至少55个核苷酸，常见的是至少60个核苷酸，更常见的是至少66个核苷酸，优选的是至少72个核苷酸，更优选的是至少79个核苷酸，而在特别优选实施方案中是至少85个或更多个核苷酸。不同遗传序列的片段通常可以在适当长度的序列段上彼此进行比较，特别是诸如下述结构域等特定的片段。
编码DTLR2-10的核酸特别适用于鉴定那些编码自身或密切相关蛋白的基因、mRNA和cDNA，以及编码多形性变体、等位变体或其他遗传变体的DNAs，如来源于不同个体或相关物种的变体。这些筛选方法的优选探针是在不同多形性变体中保守的白介素区域，或含有缺乏特异性的核苷酸的区域，优选的则是全长或近似全长的区域。在其他情况下，多形性变体特异性序列会具有更大的作用。
本发明还包括含有与上述分离DNA相同或高度同源的核酸序列的重组核酸分子和片段。具体地说，这些序列通常与调控转录、翻译及DNA复制的DNA片段有效联接。这些附加片段通常能协助所需核酸片段的表达。
当同源核酸序列或高度同一的核酸序列彼此比较或与表2-10所示序列比较时，可表现出明显的相似性。核酸的同源性标准可采用该领域常用的通过序列比较获得同源性的方法，也可根据杂交条件来确定。下文将更详细地描述用于比较的杂交条件。
核酸序列比较中的基本相同是指，比较片段或其互补链在通过适当的核苷酸插入或缺失而实现优化排列后，其核苷酸的同一性至少约为60％，一般是至少66％，普通的是至少71％，通常是至少76％，更多的是至少80％，常见的是至少84％，更常见的是至少88％，典型的是至少91％，更典型的是至少约93％，优选的是至少约95％，更优选的是至少约96-98％或更高，而在特别实施方案中则高达约99％或更高，包括，例如，编码结构域的片段，如下文描述的片段。作为选择，基本相同还可以指片段能够在选择性杂交条件下与一种链或其互补链杂交，该链通常采用来源于表2-10的一种序列。典型的选择性杂交出现在至少约14个核苷酸的序列段具有至少约55％同源性的情况下，更典型的是具有至少约65％的同源性，优选的是具有至少约75％的同源性，更优选的是具有至少约90％的同源性。参考Kanehisa(1984)Nucl.AcidsRes.12203-213，其内容在此引入作为参考。进行上述同源性比较的序列段可以具有更长的长度，在某些实施方案中，该序列段至少长约17个核苷酸，一般是至少长约20个核苷酸，普通的是至少长约24个核苷酸，常见的是至少长约28个核苷酸，典型的是至少长约32个核苷酸，更典型的是至少长约40个核苷酸，优选的是至少长约50个核苷酸，更优选的是至少长约75-100个或更多个核苷酸。
在涉及杂交同源性的描述中，严格条件是指盐浓度、温度、有机溶剂以及杂交反应中受控制的其他典型参数的严格组合条件。常见的严格温度条件包括温度高于约30℃，更常见的是高于约37℃，典型的是高于约45℃，更典型的是高于约55℃，优选的是高于约65℃，更优选的是高于约70℃。普通的严格盐浓度条件是低于约500mM，常见的是低于约400mM，更常见的是低于约300mM，典型的是低于约200mM，优选的是低于约100mM，更优选的是低于约80mM，甚至低于约20mM。但与任何单个参数的测定值相比，参数的组合更加重要。可参考，例如，Wetmur and Dayidson(1968)J.Mol.Biol.31349-370，其内容在此引入作为参考。
作为选择，通常还可以将一种序列作为序列比较的参照序列，并将测试序列与其进行比较。当使用一种序列比较算法时，可以将测试序列和参照序列输入计算机，如果需要，还可以设定子序列坐标，并设定序列比较程序的参数。再根据设定的程序参数，由该序列比较算法计算出测试序列相对于参照序列的同一性百分率。
比较序列的最佳比对可以通过，例如，Smith and Waterman(1981)Adv.Appl.Math.2482的局部同源性算法、Needlman andWunsch(1970)J.Mol.Biol.48443的同源性比较算法、Pearsonand Lipman(1988)Proc.Nat’l Acad.Sci.USA852444的相似性搜索方法、这些算法的计算机程序(Wisconsin遗传学软件包中的GAP、BESTFIT、FASTA和TFASTA，Genetics Computer Group，575Science Dr.，Madison，WI)或通过目测来实现(通常可参考Ausubelet al.，见上文)。
例如，PILEUP就是一种有效的算法。它可以通过渐进的成对比较由一组相关序列产生多序列比对结果，以显示这些序列的关系和同一性百分率。PILEUP还可以绘制一种树状图，以显示用于产生比较结果的集簇关系。PILEUP采用的是Feng and Doolittle(1987)J.Mol.Evol.35351-360的一种简化的渐进比较方法。该方法与Higginsand Sharp(1989)CABIOS5151-153中描述的方法类似。该程序可以对300个序列进行比对，每个序列的最大长度为5,000个核苷酸或氨基酸。多序列比对的过程是先将两种最相似的序列进行成对比对，以产生这两种比对序列的簇。然后将该簇与下一个最相关序列或比对序列簇进行比对。两种序列簇的比对方法只是两种单独序列的成对比对方法的简单延伸。通过一系列的渐进性成对比对可以获得最终的比对结果。该程序的运行方法是指定特定的序列及其序列比较区域的氨基酸或核苷酸坐标，并设定程序参数。例如，可以将一种参照序列与其他测试序列进行比较，以利用下述参数来确定序列的同一性百分率默认的空位权重(3.00)、默认的空位长度权重(0.10)以及加权的末端空位。
另一种适用于计算序列同一性百分率和序列相似性百分率的算法实例是Altschul，et al.(1990)J.Mol.Biol.215403-410中描述的BLAST算法。从国家生物技术信息中心(httpwww.ncbi.nlm.nih.gov/)可以公开获得用于实现BLAST分析的软件。该算法包括，先确定高评分值的序列对(HSPs)，方法是在查询序列中确定长度为W的短字符串，该字符串与数据库序列中长度相同的字符串进行比较时能够符合或满足一些正评分阈值T。T是指邻近字符串评分阈值(Altschul，et al.，见上文)。将这些最初的邻近字符串采样结果作为起始点来进行搜索，以寻找含有这些字符串的更长的HSPs。然后将采样字符串沿每条序列进行双向延伸，只要累计比较评分值能够增加。采样字符串在每个方向上延伸的终止条件是累计比较评分值下降到比其达到的最大值低一定值X；由于一个或多个负评分值比较残基的累加而使累计评分值达到0或0以下；或到达任一序列的末端。BLAST算法的参数W、T和X确定了该算法的灵敏度和速度。BLAST程序的字符串长度(W)默认值为11，BLOSUM62评分矩阵(参考Henikoff and Henikoff(1989)Proc.Nat’l Acad.Sci.USA8910915)排列(B)默认值为50，期望值(E)默认值为10，M＝5，N＝4，并且是两条链均比较。
除计算序列的同一性百分率外，BLAST算法还可以对两种序列之间的相似性进行统计分析(可参考，例如，Karlin and Altschul(1993)Proc.Nat’l Acad.Sci.USA905873-5787)。BLAST算法提供的一种相似性度量方法是最小的总概率值(P(N))，它可作为一种指标来说明两种核苷酸或氨基酸序列之间偶然出现匹配的概率。例如，一种核酸被认为与参照序列相似的条件是，该测试核酸与参照核酸比较的最小总概率值小于约0.1，更优选的是小于约0.01，最优选的是小于约0.001。
如下文所述，两种多肽的核酸序列基本相同的另一种指标是，第一种核酸编码的多肽能够与第二种核酸编码的多肽发生免疫交叉反应。因此，一种多肽与另一种多肽基本相同的条件通常是，例如，两种肽只因保守取代而有所不同。如下文所述，两种核酸序列基本相同的另一指标是这两种分子能够在严格条件下彼此杂交。
通过核苷酸取代、核苷酸缺失、核苷酸插入以及核苷酸序列段的倒位可以很容易地对分离DNA进行修饰。这些修饰可以产生编码该蛋白或其衍生物的新DNA序列。这些修饰序列可用于产生突变蛋白(突变型蛋白质)，或用于促进不同物种的表达。表达的加强可能涉及基因扩增、转录增加、翻译增加以及其他机制。这些突变的DTLR样衍生物包括预定的或位点特异性的突变蛋白或其片段，包括由遗传密码简并性获得的沉寂突变。文中使用的“突变型DTLR”包括上述DTLR同源性定义范围内的多肽，以及具有一种通过缺失、取代或插入而与天然存在的其他DTLR样蛋白有所不同的氨基酸序列的多肽。具体地说，“位点特异性突变型DTLR”包括与表2-10的蛋白基本同源的蛋白，并且通常具有文中公开的形式的大多数生物活性或作用。
位点特异性突变位点是预先确定的，但并不要求突变体必须具有位点特异性。通过在基因中插入或去除氨基酸并使其表达可以实现哺乳动物DTLR的诱变。可以用取代、缺失、插入或其任意组合来获得最终的构建体。插入包括氨基或羧基末端的融合。可以对预定密码子进行随机诱变，再根据预期活性对表达的哺乳动物DTLR突变体进行筛选。对序列已知的DNA的预定位点进行置换突变的方法已为该领域所熟知，例如，可采用M13引物诱变方法。还可以参考Sambrook，etal.(1989)和Ausubel，et al.(1987及定期增刊)。
DNA中的突变通常不应该使编码序列脱离可读框，优选的是不会产生可杂交形成环袢或发夹等二级mRNA结构的互补区。
Beaucage and Carruthers(1981)Tetra.Letts.221859-1862中描述的亚磷酰胺法可用于产生适当的合成DNA片段。获得双链片段的方法通常是合成互补链并使链在适当条件下退火，或是将互补链与适当的引物序列混合并用DNA聚合酶来产生。
通常可以用聚合酶链反应(PCR)技术来实现诱变。作为选择，诱变引物法也是在预定位点产生特定突变的常用方法。可参考，例如，Innis，et al.(1990年版)《PCR方法及应用指南》Academic Press，San Diego，CA；和Dieffenbach and Dyeksler(1995年版)《PCR引物实验手册》Cold Spring Harbor Press，CSH，NY。
IV.蛋白、肽如上所述，本发明包括灵长类动物的DTLR2-10，如具有表2-10所示序列的DTLR2-10，以及上文描述的其他形式。此外还涉及等位变体和其他变体，包括，例如，将这些序列的某些部分与表位标记或功能结构域等其他部分相结合的融合蛋白。
本发明还提供一些重组蛋白，例如用啮齿动物的这些蛋白的片段产生的异源融合蛋白。异源融合蛋白是指自然条件下一般不会以这种方式融合的蛋白或蛋白片段的一种融合体。因此，DTLR与IL-1受体的融合产物是一种通过标准肽键将两种序列融合的连续蛋白分子，这种蛋白分子通常是作为单一的翻译产物而产生，并且具有每种来源肽的特性，如序列或抗原性。类似的概念也适用于异源核酸序列。
此外，还可以用IL-1受体或其他DTLRs等相关蛋白的类似的功能域或结构域来组合产生新构建体，这些相关蛋白包括物种变体。例如，可以将不同的新融合多肽或多肽片段之间的配体结合区或其他区域进行“交换”。可参考，例如，Cunningham，et al.(1989)Science2431330-1336；和O’Dowd.et al.(1988)J.Biol.Chem.26315985-15992，其内容均在此引入作为参考。因此，通过受体结合特性的功能性联接可以产生具有新特性组合的新嵌合多肽。例如，可以添加其他相关受体分子的配体结合区，也可以将其替换成该分子或相关蛋白的其他结构域。所得蛋白通常具有组合的功能和特性。例如，融合蛋白可含有一种能够使其局限于特定亚细胞器的定向结构域。
候选的融合配偶体及序列可选自不同的序列数据库，如GenBank，c/o IntelliGenetics，Mountain View，CA；和BCG，University ofWisconsin Biotechnology Computing Group，Madison，WI，其内容均在此引入作为参考。
本发明特别提供一些能够与Toll配体结合并且(或者)在信号转导中受影响的突变蛋白。人DTLR1-10与IL-1家族其他成员的结构比较可说明其具有保守的性质(残基)。例如可参考图3A。人DTLR序列与IL-1家族其他成员的比较结果显示出结构及功能上的多种共性。还可参考Bazan，et al.(1996)Nature379591；Lodi，et al.(1994)Science2631762-1766；Sayle and Milner-White(1995)TIBS20374-376；和Gronenberg，et al.(1991)ProteinEngineering4263-269。
IL-1α和IL-1β配体能够与作为初级受体的I型IL-1受体结合，继而该复合物能够与III型IL-1受体形成高亲和性受体复合物。这些受体亚基有可能是IL-1家族新成员的共用受体。
DTLR2-10序列的其他物种对应物中的类似变异，例如在对应区域中的类似变异，应能够产生与配体或底物相互作用的类似功能。特别优选的是用小鼠序列或人序列进行替换。反之，配体结合相互作用区以外的保守取代可以使大多数信号活性得以保留。
灵长类动物DTLR2-10的“衍生物”包括氨基酸序列突变体、糖基化变体、代谢衍生物以及与其他化学基团的共价结合物或聚集物。共价衍生物的制备方法可以是，例如，用该领域熟知的方法使功能基团与DTLR氨基酸侧链或N-或C-末端的基团进行联接。这些衍生物可包括羧基末端的或含羧基侧链残基的脂肪族酯类衍生物或酰胺类衍生物、含羟基残基的O-酰基衍生物，以及氨基末端氨基酸或赖氨酸或精氨酸等含氨基残基的N-酰基衍生物，但不局限于此。酰基可选自烷基基团，包括C3-C18标准烷基，因此形成的是烷酰芳酰类衍生物。
具体地说，糖基化衍生物包括，例如，通过在多肽合成及加工过程中或在进一步的加工过程中改变其糖基化模式而产生的糖基化衍生物。其实现的特别优选方法是将这种多肽暴露于由正常情况下能够进行这种加工的细胞获得的糖基化酶，如哺乳动物糖基化酶。还可以考虑去糖基化酶。此外还包括一级氨基酸序列相同但含有其他次要修饰的形式，包括磷酸化氨基酸残基，如磷酸酪氨酸、磷酸丝氨酸或磷酸苏氨酸。
主要的一组衍生物是这些受体或其片段与其他蛋白的共价偶联物。这些衍生物可以通过诸如N-末端或C-末端融合体的重组培养物来加以合成，也可以利用该领域已知的能够通过活性侧链基团与蛋白交联的制剂来合成。与交联制剂的优选衍生化位点是游离氨基、糖类基团，以及半胱氨酸残基。
此外还提供这些受体与其他同源或异源蛋白的融合多肽。同源多肽可以是不同受体的融合体，由此可以产生，例如，一种对多种不同Toll配体具有结合特异性的杂合蛋白，或一种对底物作用的特异性变宽或减弱的受体。也可以构建具有衍生蛋白组合特性或活性的异源融合体。典型的实例是萤光素酶等报告多肽与配体结合区等受体片段或受体结构域的融合体，这样可以很容易地检测特定配体的存在情况或定位。可参考，例如，Dull，et al.，美国专利4,859,609，其内容在此引入作为参考。其他基因融合配偶体包括谷胱甘肽-S-转移酶(GST)、细菌β-半乳糖苷酶、trpE、蛋白A、β-内酰胺酶、α-淀粉酶、乙醇脱氢酶和酵母α交配因子。可参考，例如，Godowski，et al.(1988)Science241812-816。
Beaucage and Carruthers(1981)Tetra.Letts.221859-1862中描述的亚磷酰胺法可用于产生适当的合成DNA片段。获得双链片段的方法通常是合成互补链并使链在适当条件下退火，或是将互补链与适当的引物序列混合并用DNA聚合酶来产生。
这些多肽还可以含有已被化学修饰的氨基酸残基，如磷酸化、磺化、生物素化，或被添加或去除了其他基团，特别是分子形状与磷酸基团类似的基团。一些实施方案中的修饰是有效的标记试剂或纯化目标，如亲和配体。
融合蛋白的制备一般可以通过核酸重组法或多肽合成法来实现。有关核酸操作及表达技术的综合描述，可参考，例如，Sambrook，etal.(1989)《分子克隆实验手册》(第二版)，Vols.1-3，Cold SpringHarbor Laboratory和Ausubel，et al.(1987年版及定期增刊)《最新分子生物学实验方法》，Greene/Wiley，New York；其内容均在此引入作为参考。有关多肽合成技术的描述，可参考，例如，Merrifield(1963)J.Amer.Chem.Soc.852149-2156；Merrifield(1986)Science232341-347；和Atherton，et al.(1989)《固相肽合成实验方法》，IRL Press，Oxford；其内容均在此引入作为参考。有关制备较长多肽的方法，还可以参考Dawson，et al.(1994)Science266776-779。
本发明还涉及除氨基酸序列变体或糖基化变体之外的其他DTLR2-10衍生物的应用。这些衍生物可包括与化学基团的共价结合物或聚集物。这些衍生物通常可分为3类(1)盐类衍生物，(2)侧链及末端残基的共价修饰物，以及(3)吸附复合物，例如吸附于细胞膜的复合物。这些共价衍生物或聚集物可作为免疫原，也可作为免疫测定法中的试剂，还可以作为诸如用于亲和纯化受体或抗体等其他结合分子的纯化方法中的试剂。举例来说，可以用该领域熟知的方法将Toll配体通过共价结合固定在一种固体支持物上，如固定在溴化氰活化的Sepharose上，也可以通过或不通过戊二醛交联将Toll配体吸附于聚烯烃表面，从而用于DTLR受体、抗体或其他类似分子的测定或纯化。还可以用一种可检测基团标记该配体，例如用氯胺T方法进行放射性碘标记，或与稀土螯合物共价结合，或与另一种荧光基团偶联，从而用于诊断测定。
本发明的DTLR可作为抗原，用于产生对该DTLR或其不同片段具有特异性的抗血清或抗体，例如能使其有别于其他IL-1受体家族成员。纯化的DTLR可用于筛选由包含该蛋白的混合制品免疫获得的单克隆抗体或抗原结合片段。术语“抗体”还特别包括天然抗体的抗原结合片段，如Fab、Fab2、Fv等。纯化的DTLR还可作为试剂，用于检测随表达水平提高而产生的抗体或导致产生抗内源受体抗体的免疫学病症。此外，还可以如下文所述，将DTLR片段作为免疫原用于产生本发明的抗体。例如，本发明涉及一些对表2-10所示氨基酸序列或其片段或多种同源肽具有结合亲和力或由其诱发产生的抗体。本发明还特别涉及一些对可能暴露或确实暴露于天然DTLR蛋白外表面的特定片段具有结合亲和力或由这些片段诱发产生的抗体。
抑制配体与受体结合的结果可能是通过竞争性抑制来阻断对该受体配体的生理学反应。因此，本发明的体外测定方法通常是采用抗体、这些抗体的抗原结合区，或与固相底物连接的片段。这些测定方法还可用于诊断测定配体结合区突变或修饰的影响，或诸如影响信号功能或酶功能的其他突变和修饰的作用。
本发明还涉及竞争性药物筛选测定法的应用，例如用受体的中和抗体或其片段来竞争测试化合物与配体或其他抗体的结合。由此可利用中和抗体或其片段来检测具有一种或多种受体结合位点的多肽的存在情况，还可用来占据受体上可能与配体结合的结合位点。
V.核酸及蛋白的制备编码蛋白或其片段的DNA的获得方法可以是化学合成、筛选cDNA库，或筛选由多种细胞系或组织样品制备的基因组库。天然序列的分离可采用标准的方法，诸如文中的表2-10提供了这些序列。其他物种的对应物的鉴定可采用杂交技术、或不同的PCR技术，并结合或采用搜索GenBank等序列数据库的方法。
该DNA可以在多种不同的宿主细胞中表达，以合成可继而用于，例如，产生多克隆抗体或单克隆抗体的全长受体或其片段；用于结合测定；用于构建并表达经过改造的配体结合区或激酶/磷酸酶结构域；并用于结构/功能研究。变体或片段的表达可以在适当表达载体转化或转染的宿主细胞中进行。除含有来自重组宿主的杂质之外，这些分子可以基本上不含其他蛋白杂质或细胞杂质，因而特别适合与一种药学容许的载体和/或稀释剂组合而作为药用组合物使用。该蛋白或其片段可作为与其他蛋白的融合体来加以表达。
表达载体通常是含有所需受体基因或其片段的自我复制型DNA或RNA构建体，其中的基因或其片段通常与一些能够被适当宿主细胞识别的适当遗传调控元件有效连接。这些调控元件能够在适当宿主内影响表达。为影响表达所必需的特定调控元件的类型取决于最终使用的宿主细胞。这些遗传调控元件通常可包含一种原核启动子系统或一种真核启动子表达调控系统，典型的则还包含一种转录启动子、一种可选的用于调控转录起始的操纵基因、用于提高mRNA表达水平的转录增强子、一种编码适当核糖体结合位点的序列，以及终止转录和翻译的序列。表达载体通常还可以包含一种复制起始点，以使该载体的复制不依赖于宿主细胞。
本发明的载体包括那些含有所述蛋白编码DNA或编码等效生物活性多肽的DNA片段的载体。这些DNA可以用病毒启动子来调控，也可以编码一种选择标记。本发明还涉及这些表达载体的应用，这些载体能够在原核或真核宿主中表达真核蛋白的编码cDNA，其中，所述载体与所述宿主相容，并且在所述载体中插入有真核受体的编码cDNA，从而使含有该载体的宿主在生长时能够表达所述cDNA。表达载体通常被设计成能够在其宿主细胞内稳定复制或扩增，从而极大地提高每个细胞中的所需基因总拷贝数。表达载体在宿主细胞内复制的能力并不总是必需具备的条件，例如，可以用不含能被宿主细胞识别的复制起始点的载体在多种宿主中实现该蛋白或其片段的瞬时表达。此外，还可以使用能通过重组将蛋白编码区或其片段整合到宿主DNA中的载体。
文中描述的载体包括质粒、病毒、细菌噬菌体、整合型DNA片段，以及能够使DNA片段整合到宿主基因组中的其他载体。表达载体是一些含有遗传调控元件的特化载体，这些调控元件可影响与其有效连接的基因的表达。质粒是最常用的载体，但该领域已了解或将要了解的其他所有功能等价载体都适合于在本发明中使用。可参考，例如，Pouwels，et al.(1985及增刊)《克隆载体实验手册》Elsevier，N.Y.和Rodriquez，et al.(eds.)《载体分子克隆载体及其应用概论》Buttersworth，Boston，1988，其内容均在此引入作为参考。
转化细胞是已被利用DNA重组技术构建的受体载体转化或转染的细胞，优选的是哺乳动物细胞。被转化的宿主细胞通常可表达所需蛋白或其片段，但如果是用于其DNA的克隆、扩增和操作，则这些转化细胞无需表达目的蛋白。本发明还涉及将转化细胞培养在营养培养基中，从而使所述受体能够聚集在细胞膜上。可以从培养物中回收目的蛋白，在某些情况下，也可以从培养基中回收目的蛋白。
就本发明而言，可以将功能上相关的核酸序列彼此有效连接。举例来说，可以将一种原序列或分泌型导肽与一种多肽的DNA有效连接，条件是这种这种原序列或分泌型导肽可作为原蛋白表达，或可参与将所述多肽引导至细胞膜，或可参与所述多肽的分泌。可以将一种启动子与编码序列有效连接，条件是这种启动子可调控该多肽的转录；还可以将核糖体结合位点与编码序列有效连接，条件是这种核糖体结合位点的定位能够使翻译得以进行。有效连接通常是指邻接并且可读框吻合，但有些遗传元件，如阻抑物基因，不与操纵子序列邻接，而只是与其连接并调控其表达。
适当的宿主细胞包括原核细胞、低等真核细胞和高等真核细胞。原核细胞包括革兰氏阴性生物和革兰氏阳性生物，如大肠杆菌和枯草芽孢杆菌。低等真核细胞包括酵母，如酿酒酵母和毕赤酵母，以及网柄菌属中的物种。高等真核细胞包括由动物细胞建立的组织培养细胞系，包括非哺乳动物来源的细胞，如昆虫细胞和鸟类细胞，还包括哺乳动物来源的细胞，如人、灵长类动物和啮齿动物的细胞。
原核宿主-载体系统包括多种用于不同物种的载体。文中使用的大肠杆菌及其载体一般包括用于其他原核细胞的等价载体。用于DNA扩增的典型载体是pBR322或其多种衍生物。用于表达受体或其片段的载体包括那些含有lac启动子(pUC系列)；trp启动子(pBR322-trp)；Ipp启动子(pIN系列)；λ-pP或pR启动子(pOTS)；或杂合启动子，如ptac(pDR540)，但不局限于此。可参考《载体分子克隆载体及其应用概论》(eds.Rodriquez and Denhardt)，Buttersworth，Boston，第10章，pp.205-236中的Brosius，et al.(1988)“采用λ-、trp-、lac-及Ipp-衍生启动子的表达载体”。
可以用含有DTLR系列的载体转化低等真核细胞，如酵母和网柄菌属细胞。就本发明而言，最常用的低等真核细胞宿主为面包酵母，即酿酒酵母。一般是将其作为典型的低等真核细胞，但也可以使用其他多种菌株和物种。酵母载体通常含有一种复制起始点(整合型除外)、一种选择基因、一种启动子、受体或其片段的编码DNA，以及翻译终止序列、多腺苷酸化序列和转录终止序列。适当的酵母表达载体可含有组成型启动子，如3-磷酸甘油酸激酶启动子和其他多种糖酵解酶基因启动子，也可含有诱导型启动子，如乙醇脱氢酶2启动子或金属硫蛋白启动子。适当的载体包括下述类型的衍生物自我复制的低拷贝型(如YRp-系列)、自我复制的高拷贝型(YEp-系列)；整合型(YIp-系列)或微小染色体(如YCp-系列)。
高等真核组织培养细胞一般是用于表达功能活性白介素蛋白的优选宿主细胞。原则上可以使用任何非脊椎动物或脊椎动物来源的高等真核组织培养细胞系，如昆虫杆状病毒表达系统。这些细胞的转化或转染以及增殖已成为常规的方法。可使用的细胞系实例包括HeLa细胞、中国仓鼠卵巢(CHO)细胞系、幼鼠肾(BRK)细胞系、昆虫细胞系、鸟类细胞系，以及猴(COS)细胞系。这些细胞系的表达载体通常含有一种复制起始点、一种启动子、一种翻译起始位点、RNA剪接位点(如果使用基因组DNA)、一种多腺苷酸化位点和一种转录终止位点。这些载体特别还可以包含一种选择基因或扩增基因。适当的表达载体可以是带有来源于诸如腺病毒、SV40、细小病毒、痘苗病毒或巨细胞病毒等的启动子的质粒、病毒或逆转录病毒。适当表达载体的典型实例包括pCDNA1；pCD，参考Okayama，et al.(1985)Mol.CellBiol.51136-1142；pMClneo PolyA，参考Thomas，et al.(1987)Cell51503-512；和杆状病毒载体，如pAC373或pAC610。
分泌型蛋白的可读框通常编码一种多肽，该多肽含有一种在其N端与信号肽共价连接的成熟产物或分泌产物。该信号肽在成熟多肽或活性多肽分泌之前被剪切。剪切位点可通过经验法则高度精确地加以预测，如von-Hei jne(1986)Nucleic Acids Research144683-4690，而信号肽的精确氨基酸组成似乎不对其功能起关键性作用，如Randall，et al.(1989)Science2431156-1159；Kaiser，et al.(1987)Science235312-317。
经常会希望在某种系统中以特定或规定的糖基化模式来表达这些多肽。在这种情况下，通常是获得由表达系统天然产生的糖基化模式。但也可以对这种模式进行修饰，方法是将多肽，如非糖基化形式的多肽，暴露于被引入到异源表达系统中的适当糖基化蛋白。例如，可以将一种或多种编码哺乳动物糖基化酶或其他糖基化酶的基因与受体基因进行共转化。利用这种方法可以在原核细胞或其他细胞内获得某些哺乳动物糖基化模式。
DTLR的来源可以是表达重组DTLR的真核或原核宿主，如上文描述的宿主。此外还可以是小鼠Swiss 3T3成纤维细胞等细胞系，但本发明还涉及其他哺乳动物细胞系，优选的则是来源于人的细胞系。
由于序列为已知，因而可通过传统的肽合成方法来制备灵长类动物DTLRs或其片段或衍生物。这些方法包括，例如，Stewart and Young(1984)《固相肽合成》，Pierce Chemical Co.，Rockford，IL；Bodanszky and Bodanszky(1984)《肽合成的实践方法》，Springer-Verlag，New York；和Bodanszky(1984)《肽合成原理》，Springer-Verlag，New York中描述的方法，其内容均在此引入作为参考。举例来说，可以使用叠氮法、酰基氯法、酸酐法、混合酐法、活化酯法(如对硝基苯酯、N-羟基琥珀酰亚胺基酯，或氰基甲酯)、碳化二亚胺唑法、氧化还原法，或二环己基碳二亚胺(DCCD)/附加剂法。上述方法可采用固相和液相合成。部分DTLR序列也可采用类似的技术。
根据上文描述的常用肽合成方法可以制备出适当的DTLR蛋白或其片段或衍生物，一般可通过所谓的逐步方式来进行，该方式包括将氨基酸按照序列逐个与末端氨基酸缩合，也可以用肽段与末端氨基酸结合。结合反应中不使用的氨基通常需加以保护，以避免在错误位置发生结合。
如果采用固相合成法，则可通过羧基将C-末端氨基酸结合于一种不溶性载体或支持物。不溶性载体要能够与活性羧基结合，除此之外并没有特别的限制。不溶性载体的实例包括卤甲基树脂，如氯甲基树脂或溴甲基树脂，羟甲基树脂、苯酚树脂、叔-烷氧基羰基肼化树脂，等等。
肽的逐步合成可通过氨基被保护的氨基酸的依次结合来实现，这种氨基酸的活性羧基能够与此前形成的肽或肽链上的活性氨基缩合。当合成了全部序列之后，可以使肽与不溶性载体分离，以获得所需的肽。有关这种固相方法的综合描述，可参考Merrifield，et al.(1963)J.Am.Chem.Soc.852149-2156，其内容在此引入作为参考。
利用肽分离方法可以从反应混合物中分离和纯化出已制备好的肽及其片段，例如可采用抽提、沉淀、电泳、不同形式的层析等方法。根据预期的应用，可以获得不同纯度的本发明所述受体。可以用下文公开的蛋白纯化技术来进行纯化，也可以用免疫吸附亲和层析方法中描述的抗体来进行纯化。免疫吸附亲和层析的实施方法是，先将抗体与固体支持物连接，再用连接的抗体与适当细胞的增溶裂解物、表达该受体的其他细胞的裂解物，或经过DNA技术处理而能够产生该蛋白的细胞的裂解物或上清液相接触，见下文。
一般而言，纯化蛋白的纯度至少约为40％，普通的是至少约50％，常见的是至少约60％，典型的是至少约70％，更典型的是至少约80％，优选的是至少约90％，更优选的是至少约95％，而在特别实施方案中是至少约97％-99％或更高。纯度一般是根据重量来计算，但也可以根据摩尔数来计算。可以根据需要采用不同的测定方法。
VI.抗体灵长类动物等不同哺乳动物的DTLR蛋白及其片段都可用于产生抗体，这些蛋白及其片段可以是自然界中存在的天然形式，也可以是重组形式，其区别在于天然受体的抗体更可能识别只以天然构象存在的表位。变性抗原的检测也具有应用价值，例如可用于蛋白印迹分析。此外还包括抗独特型抗体，这些抗体可作为天然受体或抗体的激动剂或拮抗剂使用。
优选的抗体应同时具备亲和性和选择性。通常是优选高亲和性，而选择性能够使抗体鉴别不同亚类的实施方案。具体地说，理想的是获得一些能够与，例如，不同特定组合的相关成员特征性结合但不与其他成员结合的抗体制剂。这些不同的亚类组合可以特异性地形式，例如，可利用免疫亲和、筛选等标准方法来产生或筛选这些试剂。
对蛋白的特定片段具有抗性的抗体，包括结合片段和单链型抗体，可通过将该片段与免疫原性蛋白的结合物对动物进行免疫的方法来产生。单克隆抗体可由分泌该抗体的细胞获得。可以根据与正常蛋白或缺陷型蛋白的结合能力对这些抗体进行筛选，也可以根据激动活性或拮抗活性进行筛选。这些单克隆抗体通常能够以至少约1mM的KD进行结合，更多的是至少约300μM，典型的是至少约100μM，更典型的是至少约30μM，优选的是至少约10μM，更优选的是至少约3μM或更低。
本发明的抗体，包括抗原结合片段，可具有明显的诊断或治疗价值。这些抗体可作为强拮抗剂与其受体结合，并抑制配体的结合或该受体引发生物学应答的能力，例如对其底物的作用。这些抗体还可作为非中和性抗体使用，并且可联接于毒素或放射性核素，使其能够与产生白介素的细胞或定位于白介素产生源的细胞相结合。
此外，还可以将这些抗体直接或通过连接物间接偶联于药物或其他治疗剂。
本发明的抗体还可用于诊断性应用。这些抗体可作为俘获抗体或非中和性抗体与受体结合，但不抑制配体或底物的结合。这些抗体可作为中和抗体用于竞争性结合测定。此外还可用于配体的检测或定量。这些抗体可作为试剂用于蛋白印迹分析，或用于相应蛋白的免疫重叠或免疫纯化。
由于融合的或共价联接的多肽可作为免疫原使用，因而可以将蛋白片段与其他物质相联接，特别是与多肽相联接。哺乳动物DTLR及其片段可以与多种免疫原融合或共价联接，如钥孔血兰素、牛血清白蛋白、破伤风类毒素，等等。有关多克隆抗血清制备方法的描述，可参考《微生物学》，Hoeber Medical Division，Harper and Row，1969；Landsteiner(1962)《血清反应的特异性》，Dover Publications，New York；和Williams，et al.(1967)《免疫学及免疫化学方法》，Vol.1，Academic Press，New York；其内容均在此引入作为参考。典型的方法涉及用一种抗原对动物进行超免疫。再于重复免疫短时间后收集动物血并分离γ球蛋白。
有时需要由多种哺乳动物宿主制备单克隆抗体，如小鼠、啮齿动物、灵长类动物、人，等等。有关这些单克隆抗体制备技术的描述，可参考，例如，Stites，et al.(eds.)《基础及临床免疫学》(第四版)，Lange Medical Publications，Los Altos，CA及其参考文献；Harlow and Lane(1988)《抗体实验手册》，CSH Press；Goding(1986)《单克隆抗体原理及实践》(第二版)Academic Press，NewYork；特别参考Kohler and Milstein(1975)Nature256495-497中讨论的一种产生单克隆抗体的方法。这些文献均在此引入作为参考。简单地说，该方法涉及用一种免疫原对动物进行注射。然后将动物处死并取其脾细胞，再将这些细胞与骨髓瘤细胞融合。所得的杂合细胞或“杂交瘤”能够在体外繁殖。然后对杂交瘤群体进行筛选，以分离出单克隆，每种克隆可分泌单一种类的抗免疫原抗体。由此获得的单种抗体是无限增殖的克隆化单个B细胞的产物，这些细胞是免疫动物在对免疫原性物质上的特定识别位点产生应答的过程中产生的。
其他适当技术则涉及在体外将淋巴细胞暴露于抗原性多肽，作为选择，还可以对噬菌体或其他载体中携带的抗体库进行筛选。可参考Huse，et al.(1989)“在λ噬菌体中产生大型免疫球蛋白组合库”，Science2461275-1781；和Ward.et al.(1989)Nature341544-546，其内容均在此引入作为参考。本发明的多肽和抗体可经过改造或不经改造加以使用，如嵌合抗体或人源化抗体。通常可以将多肽和抗体进行标记，方法是与一种提供可检测信号的底物共价或非共价结合。已知有多种标记和结合物可以使用，并且在科技文献和专利文献中有广泛的描述。适当的标记包括放射性核素、酶、底物、辅因子、抑制剂、荧光基团、化学发光基团、磁性颗粒，等等。讲述这些标记的使用方法的专利包括美国专利3,817,837；3,850,752；3,939,350；3,996,345；4,277,437；4,275,149；和4,366,241。此外还可以产生重组的或嵌合的免疫球蛋白，可参考Cabilly，美国专利4,816,567；也可以在转基因小鼠中产生，可参考Mendez，et al.(1997)Nature Genetics15146-156。这些文献均在此引入作为参考。
本发明的抗体还可用于DTLRs的亲和层析分离。在制备的层析柱中，可以将抗体连接于一种固体支持物，如琼脂糖、Sephadex等颗粒，然后使细胞裂解物过柱，洗涤，再用浓度递增的温和变性剂过柱，由此释放出纯化的蛋白。该蛋白可用于纯化抗体。
这些抗体还可用于在表达库中筛选特定的表达产物。该方法中使用的抗体通常带有一种标记基团，以便于通过抗体结合来检测抗原的存在情况。
用DTLR诱发的抗体还可用于产生抗独特型抗体。这些抗体可用于检测或诊断与该蛋白的表达有关或与表达该蛋白的细胞有关的多种免疫学病情。这些抗体还可作为配体的激动剂或拮抗剂使用，这些抗体可能是天然配体的竞争性抑制物，也可能是天然配体的替代物。
利用免疫测定法通常可检测出能够与一种抗体，例如用含有SEQID NO4、6、8、10、12、14、16、18、20、22或24所示氨基酸序列的一种特定免疫原诱发产生的抗体，发生特异性结合或特异性免疫反应的DTLR蛋白。该免疫测定法通常使用一种多克隆抗血清，例如用SEQ ID NO4、6、8、10、12、14、16、18、20、22或24的一种蛋白诱发产生的抗血清。这种抗血清经过筛选而对DTLR1等其他IL-1R家族成员具有低交叉反应性，优选的则是对相同物种的其他IL-1R家族成员具有低交叉反应性，在用于免疫测定之前，可通过免疫吸附来去除所有的交叉反应性。
为了产生用于免疫测定的抗血清，可以按文中所述分离出SEQ IDNO4、6、8、10、12、14、16、18、20、22或24的蛋白或其组合。例如，可以在哺乳动物细胞系中产生重组蛋白。用选定的蛋白对适当宿主进行免疫，例如对Balb/c等近交系小鼠进行免疫，免疫一般采用标准的佐剂，如弗氏佐剂，并使用标准的小鼠免疫方案(参考Harlowand Lane，见上文)。作为选择，按本文所示序列合成并与一种载体蛋白连接的合成肽也可作为免疫原使用。收集多克隆血清，并利用免疫测定法，例如将免疫原固定在固体支持物上的固相免疫测定法，对免疫原蛋白进行滴定。选择那些效价为104或更高的多克隆抗血清，并利用上文Harlow and Lane第570-573页中描述的竞争性结合免疫测定法检验这些抗血清对小鼠DTLRs或人DTLR1等其他IL-1R家族成员的交叉反应性。优选的是在该测定中至少将两种DTLR家族成员与人DTLR2-10中的一些蛋白协同检测。这些IL-1R家族成员可以是通过文中描述的标准分子生物学及蛋白化学技术产生并分离的重组蛋白。
交叉反应性的测定可采用竞争性结合免疫测定法。举例来说，可以将SEQ ID NO4、6、8、10、12、14、16、18、20、22和/或24的蛋白或其不同的片段固定在一种固体支持物上。测试反应中添加的蛋白可以对固定化抗原与抗血清的结合产生竞争作用。将上述蛋白对固定化蛋白与抗血清结合的竞争能力同SEQ ID NO4、6、8、10、12、14、16、18、20、22和/或24的蛋白进行比较。利用标准方法计算出上述蛋白的交叉反应性百分率。挑选并合并那些与每种上述蛋白的交叉反应性低于10％的抗血清。然后用上述蛋白对合并的抗血清进行免疫吸附，以去除交叉反应性抗体。
然后将免疫吸附的合并抗血清用于上文描述的竞争性结合免疫测定，以此将第二种蛋白与免疫原蛋白(如SEQ ID NO4、6、8、10、12、14、16、18、20、22和/或24的IL-1R样蛋白)进行比较。为了进行比较，可以在较宽的浓度范围内对这两种蛋白均进行检测，并确定每种蛋白在50％抑制固定化蛋白与抗血清结合时的必需量。如果第二种蛋白的必需量低于一种或多种选定蛋白的必需量的两倍，则可认为这第二种蛋白能够与免疫原诱发产生的抗体特异性结合。
应该了解的是，这些DTLR蛋白属于一种同源蛋白家族，迄今为止，该家族至少包括10种已确认的基因。对DTLR2-10等特定的基因产物而言，该术语不仅是指文中公开的氨基酸序列，而且还涉及属于等位变体、非等位变体或物种变体的其他蛋白。此外，该术语还包括非天然突变体，其突变的引入方法可以是利用单点突变等常规重组技术故意产生突变，也可以是将相应蛋白编码DNA的小段序列切除，还可以是替换成新氨基酸或添加新氨基酸。这些微小变体必须要基本保持原分子的免疫特性和/或生物活性。因此，这些变体包括能够与指定的天然IL-1R相关蛋白，如SEQ ID NO2、4、6、8、10、12、14、16、18、20、22或24中显示的DTLR蛋白，产生特异性免疫反应的蛋白。检测变体蛋白生物学特性的方法可以是，在适当细胞系中表达该蛋白，并检测对淋巴细胞的适当影响。被认为不重要的特定蛋白修饰包括用化学性质类似的氨基酸进行保守取代，这与上文有关整个IL-1R家族的描述相同。本发明所述蛋白的成分的确定方法可以是，将蛋白与DTLR2-10的蛋白进行优化比较，以及用文中描述的传统免疫测定法来检测免疫特性。
VII.试剂盒及定量方法本发明的天然IL-1R样分子和重组IL-1R样分子均特别适合于在试剂盒及测定方法中使用。举例来说，这些方法可用于结合活性筛选，如筛选这些蛋白的配体。近几年已发展了一些自动测定的方法，因而每年可对数万种化合物进行筛选。可参考，例如，BIOMEK自动化工作站，Beckman Insturments，Palo Alto，California和Fodor，et al.(1991)Science 251767-773，其内容均在此引入作为参考。后者描述的是利用多种在固相底物上合成的特定聚合物来进行结合测试的方法。本发明可用于获得大量处于活性状态的可溶性纯化DTLRs，这非常有利于建立一些适合筛选配体或激动剂/拮抗剂同源蛋白的测定方法。
可以将纯化的DTLR直接包被在平板上，以便于在上述的配体筛选技术中使用。也可以用这些蛋白的非中和性抗体作为俘获抗体，将相应的受体固定在固相载体上，从而应用于，例如，诊断领域。
本发明还涉及将DTLR2-10及其片段、肽和融合产物应用于多种诊断试剂盒及方法，以检测该蛋白或其配体的存在情况。此外，或作为选择，还可以在这些试剂盒及方法中引入这些分子的抗体。试剂盒通常会含有一种隔室，其中装有特定的DTLR肽段或基因段，或装有能够识别肽段或基因段的试剂。肽的识别试剂通常是一种受体或抗体，基因段的识别试剂通常是一种杂交探针。
用于检测诸如DTLR4等样品浓度的优选试剂盒通常含有已知对DTLR4具有结合亲和力的一种标记化合物，如配体或抗体，一种作为阳性对照的DTLR4源(天然的或重组的)，以及将结合标记化合物与游离标记化合物分离的一种工具，如用于固定测试样品中的DTLR4的一种固相载体。通常还提供装有试剂的隔室以及说明书。
对哺乳动物DTLR或其片段具有特异性的抗体，包括抗原结合片段，或受体片段可应用于诊断领域，以检测配体和/或其片段的水平是否提高。诊断测定可以是均质的(不需要将游离试剂与抗体-抗原复合物分离的步骤)，也可以是异质的(需要一个分离步骤)。目前已有多种商品化的测定方法，如放射免疫测定法(RIA)、酶联免疫吸附测定法(ELISA)、酶免疫测定法(EIA)、酶放大免疫测定技术(EMIT)、底物标记荧光免疫测定法(SLFIA)，等等。例如，未标记抗体的使用方法是用一种标记的二抗来识别这种抗DTLR4或其特定片段的抗体。此外，在文献中已对这些测定方法进行了广泛地论述。例如，可参考Harlow and Lane(1988)《抗体实验手册》，CSH.和Coligan(1991年版及定期增刊)《最新免疫学实验方法》Greene/Wiley，New York。
抗独特型抗体在作为DTLR4的激动剂或拮抗剂方面可能具有类似的用途。在适当情况下，这些抗体也可作为治疗剂使用。
通常可将用于诊断测定的试剂以试剂盒的形式提供，以便于优化测定的灵敏度。就本发明而言，可根据测定的性质来提供测定方法和标记物、该标记物可以是标记抗体或非标记抗体，也可以是标记的配体。试剂盒中通常还包含其他附加剂，如缓冲液、稳定剂、产生信号所需的物质，如酶底物，等等。优选的是该试剂盒中还包含正确使用的说明书，以及所含试剂在使用之后的处理说明书。该试剂盒通常含有一些用于装各种有效试剂的隔室，并且带有正确使用的说明书以及试剂的处理说明书。理想的是这些试剂以冻干粉末的形式提供，当进行测定时，可将这些试剂以适当的浓度重构于一种水性介质中。
用于诊断测定的上述组分不经改变即可使用，也可以用多种方法进行调整。例如，标记的方法可以是共价或非共价连接一种直接或间接提供可检测信号的基团。在所有这些测定方法中，可以对测试化合物、DTLR或其抗体进行直接标记，也可以进行间接标记。可用于直接标记的标记基团包括125I等放射性标记、过氧化物酶和碱性磷酸酶等酶类(美国专利3,645,090)，以及可通过荧光强度、波长偏移或荧光偏振来检测变化的荧光标记(美国专利3,940,475)。这两个专利均在此引入作为参考。可用于间接标记的方法包括将一种组分生物素化，然后与偶联了一种上述标记基团的抗生物素蛋白结合。
此外，还有多种将结合配体与游离配体分离的方法，作为选择，还有多种将结合化合物与游离化合物分离的方法。可以将DTLR固定在不同的基质上，然后进行洗涤。适当的基质包括ELISA平板等塑料制品、滤器和珠。将受体固定于基质的方法包括，但不局限于，直接粘连于塑料制品、使用一种俘获抗体、化学偶联法，以及生物素-抗生物素蛋白法。该方法的最后步骤涉及利用某些方法将抗体/抗原复合物沉淀，这些方法包括，例如，使用聚乙二醇等有机溶剂，或使用硫酸铵等盐类。其他适当的分离技术包括，但不局限于，Rattle，etal.(1984)Clin.Chem.30(9)1457-1461描述的荧光素抗体磁化颗粒法和美国专利4,659,678描述的双抗体磁化颗粒分离法，其内容均在此引入作为参考。
在文献中已广泛报导了将蛋白或片段与不同标记连接的方法，在此无需详细论述。许多方法涉及利用碳化二亚胺或活性酯上的活性羧基来形成肽键，或通过巯基与氯乙酰基等活性卤素的反应来形成硫醚，或利用马来酰亚胺等活性烯烃进行连接，等等。在这些应用领域中也可以使用融合蛋白。
作为诊断性应用的另一方面，本发明涉及来源于DTLR序列的寡核苷酸或多核苷酸序列的应用。这些序列可作为探针，用于检测可能患有免疫功能障碍的患者体内的相应DTLR水平。在文献中已对RNA及DNA核苷酸序列的制备方法、标记方法和优选长度进行了大量论述。寡核苷酸探针通常应含有至少约14个核苷酸，常见的是至少约18个核苷酸，而多核苷酸可含有多达数千个碱基。可使用的标记有许多种，最常用的是放射性核素，特别是32P。但也可以使用其他技术，例如可在多核苷酸中引入生物素修饰的核苷酸。然后可将生物素作为抗生物素蛋白或抗体的结合位点，这些抗生物素蛋白或抗体可带有不同的标记，如放射性核素、荧光剂、酶，等等。作为选择，还可以使用能够识别特定双链体的抗体，包括DNA双链体、RNA双链体、DNA-RNA杂合双链体，或DNA-蛋白双链体。继而可将这些抗体标记，并在所述双链体与一种表面结合的情况下进行测定，从而在该表面上形成双链体时能够对抗体与该双链体结合的情况进行检测。将探针应用于新反义RNA的实现方法可以是任意的常规技术，包括核酸杂交技术、加减筛选技术、重组探测技术、杂交体释放翻译技术(HRT)和杂交体中止翻译技术(HART)。此外还包括聚合酶链反应(PCR)等扩增技术。
此外还涉及可用于定性或定量检测其他标记的诊断试剂盒。诊断或预后结果可能取决于多种标记的组合指征。因此，这些试剂盒可用于组合标记的测定。可参考，例如，Viallet，et al.(1989)Progressin Growth Factor Res.189-97。
VIII.治疗性应用本发明提供一些具有显著的治疗应用价值的试剂。DTLRs(天然的或重组的)及其片段、突变型蛋白受体、抗体以及确实与这些受体和抗体具有结合亲和力的化合物都可用于治疗其配体的受体表现出异常表达的疾病。这些异常通常表现为免疫功能障碍。此外，本发明对多种与配体表达异常或异常触发配体应答有关的疾病或病症也具有显著的治疗应用价值。研究表明，Toll配体可参与形态发生，如背腹极性建立，以及免疫应答，特别是原发性先天应答。可参考，例如，Sun，et al.(1991)Eur.J.Biochem.196247-254；Hultmark(1994)Nature367116-117。
可以将重组DTLRs或其突变蛋白、激动剂、拮抗剂或抗体加以纯化，然后给药于患者。这些试剂可与其他活性成分，如药学容许的常规载体或稀释剂，以及不具有生理毒性的稳定剂和赋形剂联合用于治疗。这些联合制剂可以是无菌的，例如被过滤除菌，并可将其以剂量形式在剂量瓶中冻干或在稳定水性制剂中保存。本发明还涉及非补体结合性抗体及其结合片段的应用。
可利用DTLR或其片段进行配体筛选，以鉴定对受体具有结合亲和力的分子。随后可利用生物测定方法来检测是否假定配体具有阻断内源刺激活性的竞争性结合能力。由于受体片段可阻断配体活性，因而可作为阻断剂或拮抗剂使用。此外，具有内源刺激活性的化合物可以激活受体，从而可作为激动剂来刺激配体的活性，如信号诱发活性。本发明还涉及DTLR的拮抗剂抗体的治疗性应用。
有效治疗所需的试剂量取决于多种不同的因素，包括给药方法、目标部位、患者的生理状态，以及使用的其他药剂。因此，应该对治疗剂量进行滴定，以获得最佳的安全性和效力。通常可以将这些试剂的体外剂量作为指导来确定原位给药剂量。用动物来测试对特定疾病的治疗有效剂量的方法可以为人用剂量的确定提供进一步的预指标。有关其他多种注意事项的描述，可参考，例如，Gilman，et al.(1990年版)《Goodman & Gilman’s治疗的药学基础》，第8版，Pergamon Press；和《Remington药物科学》(最新版)，MackPublishing Co.，Easton，Penn.；其内容均在此引入作为参考。这些文献还描述了给药的方法，下文也将对此进行讨论，这些给药方法包括，例如，口服给药、静脉内给药、腹膜内给药、肌内给药、经皮肤扩散，等等。药学容许的载体包括水、盐水、缓冲液，以及MerckIndex，Merck & Co.，Rahway，New Jersey中描述的其他化合物。由于假定配体与其受体之间可能具有很高的结合亲和力或周转率，因而可首先预期低剂量的这些试剂就会有效。对信号通路的研究表明，极低剂量的配体即可产生影响。因此，在含有适当载体的条件下，通常可将剂量范围预定在1mM浓度以下，典型的是约在10μM浓度以下，常见的是约在100nM以下，优选的是约在10pM(皮摩尔)以下，最优选的是约在1fM(飞摩尔)以下。通常可以用缓释制剂或缓释装置来实现连续给药。
可以将DTLRs或其片段，抗体或其片段、拮抗剂和激动剂直接给药于待治疗的宿主，也可以根据化合物的大小，将其与卵白蛋白或血清白蛋白等运载蛋白偶联，然后进行给药。可以将治疗剂以任意的传统剂量形式进行给药。可以将活性成分单独给药，但优选的是将其作为药剂提供。药剂中至少含有一种上述的活性成分，并含有一种或多种相容性载体。每种载体都要与其他成分相容，并且不会对患者造成损伤，因而必须具有药学或生理相容性。这些药剂包括适用于口服给药、直肠给药、鼻部给药，或胃肠外(包括皮下、肌内、静脉内和皮内)给药的那些药剂。这些药剂可方便地以单位剂量形式提供，并且可利用制药领域中熟知的任意方法加以制备。可参考，例如，Gilman，et al.(1990年版)《Goodman & Gilman’s治疗的药学基础》，第8版，Pergamon Press；和《Remington药物科学》最新版)，Mack Publishing Co.，Easton，Penn.；Avis，et al.(1993年版)《药物剂型胃肠外给药法》Dekker，NY；Lieberman，et al.(1990年版)《药物剂型片剂》Dekker，NY；以及Lieberman，et al.(1990年版)《药物剂型分散体系》Dekker，NY。本发明的治疗方法可与其他治疗剂联合或结合使用，特别是其他IL-1家族成员的激动剂或拮抗剂。
IX.配体上文有关Toll配体的描述可提供鉴定配体的方法。该配体应能够以适当的高亲和力与相应受体特异性结合。有多种构建体可用于对受体进行标记，以检测其配体。例如，可以直接标记DTLR，也可将其融合于二次标记型标记物，如FLAG或其他表位标记等等，这些方法均可用于实现对受体的检测。检测的方法可以是组织学方法，如用于生化纯化的亲和法，也可以是标记或筛选表达克隆的方法。还可利用双杂交选择系统，由现有的DTLR序列获得适当的构建体。可参考，例如，Fields and Song(1989)Nature340245-246。
一般而言，有关DTLRs的描述可类似地应用于分别针对DTLR2、DTLR3、DTLR4、DTLR5、DTLR6、DTLR7、DTLR8、DTLR9和/或DTLR10试剂及组合物的特定实施方案。
参考下文的实施例可以更好地了解本发明的适用范围，但这些实施例不是要将本发明限制于特定的实施方案。
实施例I.常规方法一些标准方法是来自，例如，Manistis，et al.(1982)《分子克隆实验手册》Cold Spring Harbor Laboratory，Cold SpringHarbor Press；Sambrook，et al.(1989)《分子克隆实验手册》(第二版)，1-3卷，CSH Press，NY；Ausubel，et al.，《生物学》，Greene Publishing Associates，Brooklyn，NY；或Ausubel，et al.，(1987及增刊)《最新分子生物学实验方法》，Greene/Wiley，NewYork的描述或参考文献。蛋白纯化方法包括硫酸铵沉淀法、柱层析法、电泳法、离心法、结晶法，等等。可参考，例如，Ausubel，et al.，(1987及定期增刊)；Coligan，et al.，(1996年版及定期增刊)《最新蛋白质科学实验方法》Greene/Wiley，New York；Deutschet(1990)《酶学方法》，第182卷中的“蛋白质纯化指南”和该丛书中的其他部分；以及Pharmacia，Piscataway，N.J.或Bio-Rad，Richmond，CA等制造商为其蛋白纯化制品的使用提供的参考文献。利用重组技术可以实现与适当片段的融合，例如与FLAG序列或能够被蛋白酶去除的等价序列相融合。可参考，例如，Hochuli(1989)Chemische Industrie1269-70；Setlow(ed.)《遗传工程的原理和方法》1287-98，Plenum Press，N.Y.中的Hochuli(1990)“通过金属螯合吸附来纯化重组蛋白”；以及Crowe，et al.，(1992)《QIAexpress高水平表达和蛋白纯化系统》QUIAGEN，Inc.，Chatsworth，CA。
有关标准的免疫学技术和检测方法的描述可参考，例如，Hertzenberg，et al.(1996年版)《Weir’s实验免疫学手册》1-4卷，Blackwell Science；Coligan(1991)《最新免疫学实验方法》，Wiley/Greene，NY；以及《酶学方法》第70、73、74、84、92、93、108、116、121、132、150、162和163卷。
检测血管生物学活动的方法已为该领域所熟知。包括对肿瘤或其他组织中的血管发生和血管舒张活动进行检测，例如检测动脉平滑肌增殖(可参考，例如，Koyoma et al.(1996)Cell871069-1078)、单核细胞与血管上皮的粘联(参考McEvoy，et al.(1997)J.Exp.Med.1852069-2077)，等等。还可参考Ross(1993)Nature362801-809；Rekhter and Gordon(1995)Am.J.Pathol.147668-677；Thyberg，et al.(1990)Atherosclerosis10966-990；以及Gumbiner(1996)Cell84345-357。
有关神经细胞生物学活动检测方法的描述，可参考，例如，Wouterlood《神经科学实验方法》(1995年版)第10章，Elsevier；《神经科学方法》Academic Press；以及《神经学方法》Humana Press，Totowa，NJ。有关发育系统方法学的描述，可参考，例如，Meisami(ed.)《人类生长和发育生物学手册》CRC Press；和Chrispeels(ed.)《发育生物学中的分子技术和方法》Interscience。
计算机序列分析的实现可采用，例如，现有软件程序，包括由GCG(U.Wisconsin)和GenBank活动的程序。此外，还可以使用公共序列数据库，如GenBank、NCBI、EMBO的数据库和其他数据库。可利用这些生物信息学工具来预测跨膜基序和其他重要基序。
适用于IL-10受体的多种技术也可同样适用于DTLRs，如USSN08/110,683(IL-10受体)中的技术，其内容在此完全引入作为参考。
II.新的人类受体家族缩写DTLR，DNAX Toll-样受体；IL-1R，白介素-1受体；TH，Toll同源性；LRR，亮氨酸富集重复序列；EST，表达序列标记；STS，序列标记位点；FISH，荧光原位杂交。
果蝇Toll胞质区与人白介素-1(IL-1)受体之间的序列同源性的发现使人们确信这两种分子都可触发与Rel型转录因子核定位有关的信号通路。在昆虫和脊椎动物中，这种保守的信号机制控制着在进化上比较古老的免疫应答。本发明描述的是一类新的假定人受体的分子克隆方法，这些受体的蛋白结构无论是胞内段还是胞外段都与果蝇Toll十分相似。被命名为DTLRs 1-5的五种人Toll-样受体都可能是果蝇分子的直向同源体，因而可能是人类先天免疫力中未知的重要成分；令人感兴趣的是，DTLRs在脊椎动物中的进化保守性表明这些DTLRs具有另一种与Toll在果蝇胚胎背腹形成过程中的作用相类似的功能，即作为早期形态发生模式形成过程中的调节物。多组织mRNA印迹的结果说明，人DTLRs的表达模式有显著的不同。此外，荧光原位杂交和序列标记点数据库分析的结果表明，DTLR同源基因位于4号染色体(DTLRs 1、2和3)、9号染色体(DTLR4)和1号染色体(DTLR5)上。对参与比较的多种昆虫及人DTLRs、脊椎动物IL-1受体、MyD88因子和植物抗病蛋白的Toll同源域进行结构预测，由此可发现一种带有酸性活性位点的平行β/α折叠；值得注意的是，在广泛参与细菌感觉信息传导的一类反应调节因子中也发现了与其类似的结构。
在果蝇与人的普通胚胎形状和模式中已蕴含了使其产生显著形态差异的因素，但由这些因素引发的细胞复杂性却有很大不同。DeRobertis和Sasai(1996)Nature38037-40；和Arendt andNübler-Jung(1997)Mech.Develop.617-21。昆虫与脊椎动物在发育方向上的趋异性是由非常类似的信号通路决定的，这说明由不同基因库形成的蛋白网络和生化机制具有很强的保守性。Miklos andRubin(1996)Cell86521-529；和Chothia(1994)Develop.1994Suppl.，27-33。绘制这些调节通路的进化图的有效方法是通过种间蛋白序列和结构的比较来推断其可能的分子成分(和生物学功能)。Miklos and Rubin(1996)Cell86521-529；Chothia(1994)Develop.1994 Suppl.，27-33(3-5)；和Banfi，et al.(1996)Nature Genet.13167-174。
体轴的确立，无论是由先天不对称性导致还是由外界信号触发，都是胚胎发育过程中普遍的一个关键步骤。DeRobertis and Sasai(1996)Nature38037-40；和Arendt and Nübler-Jung(1997)Mech.Develop.617-21。目前已对背腹极性形成模型系统的系统发生原理和细胞机制给予了特别的关注。DeRobertis and Sasai(1996)Nature38037-40；和Arendt and Nübler-Jung(1997)Mech.Develop.617-21。通过对果蝇胚胎的研究，人们提出了一种典型的分子策略来解释这种转变，即少量基因的顺序作用使转录因子Dorsal形成腹侧化梯度。St.Johnston and NüssleinVolhard(1992)Cell68201-219；和Morisato and Anderson(1995)Ann.Rev.Genet.29371-399。
该信号通路的中心是跨膜受体Toll，该受体可与母体分泌的腹侧因子Sp_tzle结合，然后将信号传递到胞质侧结合的辅助分子Tube，并且激活Ser/Thr激酶Pelle，这种激酶对Dorsal与其抑制剂Cactus的解离具有催化作用，从而使Dorsal能够迁移至腹侧核(Morisatoand Anderson(1995)Ann.Rev.Genet.29371-399；和Belvin andAnderson(1996)Ann.Rev.Cell Develop.Biol.12393-416)。此外，成体果蝇中的Toll通路还可以对强抗菌因子的诱导进行调控(Lemaitre，et al.(1996)Cell86973-983)；在果蝇的免疫防御中，这种作用可加强与其机制类似的IL-1通路，在脊椎动物体内，IL-1通路控制着宿主的免疫应答和炎症反应。Belvin and Anderson(1996)Ann.Rey.Cell Develop.Biol.12393-416；和Wasserman(1993)Molec.Biol.Cell4767-771。IL-1受体中的Toll相关胞质区可指导Pelle样激酶IRAK的结合以及潜伏NF-κB/I-κB复合体的激活，该复合体相当于Dorsal与Cactus的结合体。Belvin andAnderson(1996)Ann.Rev.Cell Develop.Biol.12393-416；和Wasserman(1993)Molec.Biol.Cell4767-771。
本发明描述了四种被称为DTLRs 2-5的(按Chiang and Beachy(194)Mech.Develop.47225-239的命名)新的Toll样受体的克隆方法及分子特性，与脊椎动物IL-1受体相比，这些分子构成了一种与果蝇Toll同源体关系更密切的受体家族。DTLR的序列来源于人ESTs；这些cDNAs片段被用来绘制上述五种DTLRs在人类组织中的完整表达模式和同源基因的染色体定位图谱，以及缩小用于获得全长cDNA的cDNA库的选择范围。在其他研究成果的支持下(Banfi，etal.(1996)Nature Genet.13167-174；和Wang.et al.(1996)J.Biol.Chem.2714468-4476)，我们根据结构保守性和分子简约性组装了一种与果蝇的主要调节模式相对应的人类生物系统。此外还根据Toll同源(TH)结构域的推荐三级折叠结构提出了Toll信号通路的生物学机制，该结构域是DTLRs、IL-1受体大家族、哺乳动物MyD88因子和植物抗病蛋白的共有核心组件。Mitcham，et al.(1996)J.Biol.Chem.2715777-5783；和Hardiman，et al.(1996)Oncogene132467-2475。我们认为，参与昆虫、植物和动物的形态发生及原发免疫的信号通路(Belvin and Anderson(1996)Ann.Rev.Cell Develop.Biol.12393-416；和Wilson.et al.(1997)Curr.Biol.7175-178)可能来源于细菌的双组分通路。
计算机分析利用国家生物技术信息中心(NCBI)的BLAST服务器从EST数据库(dbEST)中获得与昆虫DTLRs相关的人序列(Altschul，et al.(1994)Nature Genet.6119-129)。利用基于模式和基于图形的更灵敏的方法(Bork and Gibson(1996)Meth.Enzymol.266163-184)分离出非冗余数据库中提供的脊椎动物蛋白和植物蛋白所共有的DTLR家族信号结构域。DTLR胞内区和胞外区序列的渐进性比对是利用ClustalW来完成(Thompson，et al.(1994)NucleicAcids Res.224673-4680)；此外还通过Neighbor-Joining算法用该程序计算出比对序列的分支等级(5000次自举重复保证了3个分组结果的可信度)。
用Consensus程序(网址http://www.bork.embl-heidelberg.de/Alignment/consensus.html)绘制出严格度不同的几种保守比较图。用PRINTS蛋白指纹库(http://www.biochem.ucl.ac.uk/bsm/dbbrowser/PRINTS/PRINTS.html)在DTLRs胞外区明确鉴别出大量的亮氨酸富集重复(LRRs)(Attwood，et al.(1997)NucleicAcids Res.25212-217)，其使用的是一种能够与不同LRRs的N-端和C-端特性灵活匹配的复合基序(PRINTS代码Leurichrpt)。用三态精确度大于72％的两种预测算法推导出胞内结构域比较结果的共有二级结构，以此来提高识别的效果(Fischer，et al.(1996)FASEBJ.10126-136)。神经网络程序PHD(Rost and Sander(1994)Proteins1955-72)和统计预测方法DSC(King and Sternberg(1996)Protein Sci.52298-2310)都可以通过网络服务器来实现(链接地址分别为http://www.embl-heidelberg.de/predictprotein/phd_pred.html和http://bonsai.lif.icnet.uk/bmm/dsc/dsc_read_align.html)。胞内区可以编码THD区，有关其论述，可参考，例如，Hardiman，etal.(1996)Oncogene132467-2475；和Rock，et al.(1998)Proc.Nat’l Acad.Sci.USA95588-593，其内容均在此引入作为参考。该结构域在将磷酸基团转移至底物的受体信号机制中具有十分重要的作用。
人DTLR全长cDNAs的克隆方法利用来源于Toll样Humrsc786序列(GenBank登录号D13637)(Nomura，et al.(1994)DNA Res.127-35)的PCR引物来探测由人红白血病TF-1细胞系获得的cDNA库(Kitamura，et al.(1989)Blood73375-380)，以产生DTLRl的cDNA序列。其余的DTLR序列则来自dbEST，通过Research Genetics(Huntsville，AL)从I.M.A.G.E.协会(Lennon，et al.(1996)Genomics33151-152)获得的相应EST克隆是Clone编号80633和117262(DTLR2)、144675(DTLR3)、202057(DTLR4)以及277229(DTLR5)。人DTLRs2-4的全长cDNAs的克隆方法是分别对λgt10噬菌体、成人肺、胎盘和胎儿肝脏的5’-Stretch Plus cDNA库(Clontech)进行DNA杂交筛选；DTLR5的序列来源于人多发性硬化症斑块的EST。对所有阳性克隆进行测序和序列比较，以确定每种DTLR的ORFsDTLR1(2366bp的克隆，ORF含有786个氨基酸)、DTLR2(2600bp的克隆，ORF含有784个氨基酸)、DTLR3(3029bp的克隆，ORF含有904个氨基酸)、DTLR4(3811bp的克隆，ORF含有879个氨基酸)，以及DTLR5(1275bp的克隆，ORF含有370个氨基酸)。DTLR6-10也使用类似的方法。与DTLR3和DTLR4杂交的探针的产生方法是分别以人胎盘(Stratagene)和成人肝(Clontech)的cDNA库为模板进行PCR；引物对来源于相应的EST序列。PCR反应采用的是T.aquaticusTaqplus DNA聚合酶(Stratagene)，其反应条件如下1x(94℃ 2分钟)，30x(55℃ 20秒；72℃ 30秒；94℃ 20秒)，1x(72℃8分钟)。用于DTLR2全长cDNA筛选的探针是通过第一个EST克隆(ID#80633)的EcoRI/XbaI酶切产生的一种900bp片段。
mRNA印迹和染色体定位每道含有约2μg poly(A)+RNA的人多种组织(Cat#1，2)及癌细胞系的印迹膜(Cat#7751-1)购自Clontech(Palo Alto，CA)。用于DTLRs1-4的探针是分离的全长cDNAs，用于DTLR5的探针是EST克隆(ID#277229)质粒的插入片段。简单地说，是通过Amersham的Rediprime随机引物标记试剂盒(RPN1633)用[α-32P]dATP对探针进行放射性标记。预杂交和杂交是在65℃和0.5M Na2HPO4、7％SDS、0.5M EDTA(pH 8.0)的条件下进行。所有严格洗涤的方法都是在65℃条件下先用2xSSC、0.1％SDS洗两次，每次40分钟，再用0.1xSSC、0.1％SDS洗20分钟。然后将印迹膜置于X-射线胶片(Kodak)上，并附加增感屏，使其于-70℃曝光。通过cDNA库印迹法(14)用选定的人DTLR克隆进行更详细的研究，以检测造血细胞亚类中这些基因的表达。
按照Heng and Tsui(1994)Meth.Molec.Biol.33109-122中描述的荧光原位杂交法(FISH)用不同的全长序列(DTLRs2-4)或部分序列(DTLR5)作为探针进行人染色体制图。这些分析均由SeeDNABiotech Inc.(Ontario，Canada)完成。利用网络服务器在人-鼠畸形同源数据库(http://www.hgmp.mrc.ac.uk/DHMHD/hum_chromel.html)中搜索与定位的DTLR基因有关的人类综合症(或位于同线基因位点的小鼠缺陷)。对DTLRs6-10也可采用类似的方法。昆虫及人DTLR胞外结构域的保守结构果蝇的Toll家族至少包括四种不同的基因产物参与果蝇胚胎背腹模式形成的典型受体Toll(Morisato and anderson(1995)Ann.Rev.Genet.29371-399)，第二种是同样参与胚胎早期发育的“18Wheeler”(18w)(Chiang and Beachy(1994)Mech.Develop.47225-239；Eldon，et al.(1994)Develop.120885-899)；另两种是由雄性特异性转录本(Mst)基因位点下游的不完整Toll样ORFs预测的受体或由“序列标记位点”(STS)Dm2245(GenBank号G01378)编码的受体(Mitcham，et al.(1996)J.Biol.Chem.2715777-5783)。Toll和18w的胞外区特征性地含有约24个氨基酸的不完整LRR基序(Chiang and Beachy(1994)Mech.Develop.47225-239；和Eldon，et al.(1994)Develop.120885-899)。相似LRRs的串接排列通常可形成不同细胞表面分子的粘联性触角，其通用三级结构可能与核糖核酸酶抑制剂的马蹄形折叠架相似，其中的17个LRRs表现为一种含有28个残基的重复β/α发卡状基序(Buchanan and Gay(1996)Prog.Biophys.Molec.Biol.651-44)。有人提出，蛇根碱受体多LRR胞外域与胱氨酸折叠簇糖蛋白激素的结合可能是通过弧形β折叠的凹面来进行(Kajava，et al.(1995)Structure3867-877)，Toll对Sp_tzle的特异性识别可能也符合该模型；令人感兴趣的是，Sp_tzle和果蝇孤配体Trunk中的半胱氨酸模式预示其具有类似的胱氨酸簇三级结构(Belvin andAnderson(1996)Ann.Rev.Cell Develop.Biol.12393-416；和Casanova，et al.(1995)Genes Develop.92539-2544)。
DTLRs1-4分别具有18、19、24和22个类似的LRR排列(DTLR5不完整链目前含有近膜端的4个LRRs)，序列及模式分析(Altschul，et al.(1994)Nature Genet.6119-129；和Bork and Bibson(1996)Meth.Enzymol.266162-184)的结果表明，与其关系最为密切的是分别含有22个和31个LRR的Toll胞外域和18w胞外域(Mst ORF片段含有16个LRRs)(图1)。Toll、18w和Mst ORF的胞外域都带有位置不同的一种约90个残基的半胱氨酸富集区(与膜边界的距离分别为4、6和2个LRRs)，与此明显不同的是，人DTLR链都不包含该区域。这些半胱氨酸簇均由“顶部”(使一个LRR终止)和“底部”(叠加在一个LRR之上)这两种不同的组件构成(Chiang andBeachy(1994)Mech.Develop.47225-239；Eldon，et al.(1994)Develop.120885-899；和Buchanan and Gay(1996)Prog.Biophys.Molec.Biol.651-44)；在果蝇和人的DTLRs中，“顶部”组件还作为保守的近膜间隔区重复出现(图1)。我们认为，当“顶部”与“底部”结合时，果蝇受体(和其他LRR蛋白)中灵活定位的半胱氨酸簇可形成一种具有配对末端的紧密组件，该组件可以在不改变DTLR胞外域总体折叠的情况下插入到任一对LRRs之间；在其他蛋白的结构中也含有类似的“突出”结构域(Russell(1994)Protein Engin.71407-1410)。
TH信号结构域的分子设计通过Toll受体与I型IL-1受体(IL-1R1)的序列比较发现了一种相似性较低的胞质结构域，据推测，这种约200个氨基酸的结构域可通过类似的Rel型转录因子来调节信号通路。Belvin and Aderson(1996)Ann.Rev.Cell Develop.Biol.12393-416；和(Belvinand Aderson(1996)Ann.Rev.Cell Develop.Biol.12393-416；和Wasserman(1993)Molec.Biol.Cell4767-771)。最近发现，该功能示意图还包括两种来源于烟草和亚麻的植物抗病蛋白，其特征是含有一种N-端TH组件，随后是核苷酸结合区(NTPase)和LRR区(Wilson，et al.(1997)Curr.Biol.7175-178)；相比之下，MyD88在TH链前端含有“死亡结构域”，这是一种细胞内髓样分化标记(Mitcham，et al.(1996)J.Biol.Chem.2715777-5783；和Hardiman，et al.(1996)Oncogene132467-2475)(图1)。新IL-1型受体包括附属信号分子IL-1R3、孤受体IL-1R4(也被称为ST2/Fit-1/T1)、IL-1R5(IL-1R相关蛋白)，以及IL-1R6(IL-lR相关蛋白-2)(Mitcham，et al.(1996)J.Biol.Chem.2715777-5783；Hardiman，et al.(1996)Oncogene132467-2475)。我们已利用新的人DTLR序列对TH共用组件进行了构象分析，并针对其进化路线提出了一种结构上的解释最小的TH结构域折叠是由10个含有128个氨基酸的保守序列区决组成；比较结果中的空位标明了序列和长度可变环的可能位置(图2A-2B)。
PHD(Rost and Sander(1994)Proteins1955-72)和DSC(Kingand Sternberg(1996)ProteinSci.52298-2310)是利用多种比较序列的保守和变异模式进行预测的两种算法，由这两种算法产生的TH信号组件结果非常明显，并且彼此吻合(图2A-2B)。每个区块都含有一种不连续的二级结构元件β链(标为A-E)与α螺旋(编号1-5)交替的模式是β/α类折叠的特征，即平行β-片层的两侧表面均带有α螺旋。据推测，疏水性β-链A、C和D构成了β-片层的“内部”板条结构，而较短的两亲性β-链B和E构成了独特的“边缘”部分(图2A-2B)。这种分配方式与核心β-片层中B-A-C-D-E的β链顺序相吻合(图2C)；折叠比较(“制图法”)及识别(“穿线法”)程序(Fischer，et al.(1996)FASEB J.10126-136)可明显地重现这种双缠绕β/α拓扑结构。对TH结构域的这种大概结构进行功能预测的结果十分令人惊奇，据多序列比较结果显示，许多保守的带电残基都位于β-折叠片的C-末端βA末端的Asp16残基(区块编号方案——图2A-2B)、βB之后的Arg39和Asp40、α3的第一个转角中的Glu75，以及βD-α4环中或βE之后的保守性较低的Glu/Asp残基(图2A-2B)。其他4个保守残基(Asp7残基、Glu28残基和Arg57-Arg/Lys58残基对)的位置与β片层的对侧N末端盐桥网络相容。其他DTLR实施方案的比较结果也表现出类似的特征，特别重要的是具有这些特征的肽段，如具有这些特征的20个氨基酸的序列段。
TH结构域的信号功能依赖于其结构的完整性。目前已对IL-1R1和Toll的TH组件内的失活突变或缺失进行了分类。Heguy，et al.(1992)J.Biol.Chem.2672605-2609；Croston，et al.(1995)J.Biol.Chem.27016514-16517；Schneider，et al.(1991)GenesDevelop.5797-807；Norris and Manley.(1992)Genes Develop.61654-1667；Norris and Manley(1995)Genes Develop.9358-369；和Norris and Manley(1996)Genes Develop.10862-872。与人DTLR1-5最小化TH结构域之后的延伸链(长度分别为8、0、6、22和18个残基)最相似的是长度为4个氨基酸残基的Mst ORF短“尾”。Toll和18w则带有不相关的102个残基和207个残基的尾(图2A-2B)，其作用可能是对融合的TH结构域的信号功能进行负调节。Norris and Manley(1995)Genes Develop.9358-369；和Norris and Manley(1996)Genes Develop.10862-872。
利用由多序列比较结构产生的系统树可以最好地阐明带有TH结构域的异种蛋白之间的进化关系(图3)。4个主要的分支将植物蛋白、MyD88因子、IL-1受体和Toll样分子分隔开来；最后一个分支将果蝇和人的DTLRs分组。
人DTLR基因的染色体分布为了研究人DTLR新基因家族的遗传连锁情况，我们通过FISH对5种基因中的4种进行了染色体基因位点制图(图4)。在此之前，DTLR1基因的图谱已通过人类基因组计划而确定STS数据库中具有Humrsc786 cDNA的基因位点(dbSTS登录号G06709，相当于STSWI-7804或SHGC-12827)(Nomura，et al.(1994)DNA Res.127-35)，它将该基因定位于第4号染色体约4p14的D4S1587-D42405标记之间(50-56cM)。这一定位最近已被FISH分析结果所证实。Taguchi，et al.(1996)Genomics32486-488。我们的这项工作将剩余DTLR基因的位点定位于染色体4q32(DTLR2)、4q35(DTLR3)、9q32-33(DTLR4)和1q33.3(DTLR5)。在此期间还产生了亲本DTLR2 EST(克隆编号80633)的STS(dbSTS登录号为T57791的STS SHGC-33147)，并根据我们的检测结果将其定位于第4号染色体4q32的D4S424-D4S1548标记之间(143-153cM)。
DTLR基因的差异表达Toll和18w在果蝇体内均表现出复杂的时空表达模式，说明二者在胚胎模式形成之外可能还具有其他功能。St.Johnston andNüsslein-Volhard(1992)Cell68201-219；Morisato and Anderson(1995)Ann.Rev.Genet.29371-399；Belvin and Anderson(1996)Ann.Rev.Cell Develop.Biol.1239 3-416；Lemaitre，et al.(1996)Cell86973-983；Chiang and Beachy(1994)Mech.Develop.47225-239；和Eldon，et al.(1994)Develop.120885-899。我们已检测了DTLR转录体的空间分布，方法是用放射性标记的DTLR cDNAs对不同的人类组织和癌细胞系进行mRNA印迹分析(图5)。结果表明，DTLR1以高于其他受体的水平被广泛表达。在卵巢和脾中分别存在DTLR1的3.0kB“短”转录体和8.0kB“长”转录体(图5，A和B面)，估计这是可变剪接的结果。癌细胞mRNA的结果图表明，伯基特淋巴瘤Raji细胞系中也存在明显的DTLR1过表达(图5，C面)。DTLR2 mRNA的表达没有DTLR1那么广泛，在肺中检测到的转录体为4.0kB，而心脏、脑和肌肉中明显含有4.4kB的转录体。DTLR3的组织分布模式与DTLR2类似(图5，E面)。此外，DTLR3的转录体主要有两种，长度分别为4.0和6.0kB，并且在胎盘和胰腺中的表达水平最高。相比之下，DTLR4和DTLR5的信使转录体似乎具有很强的组织特异性。只在胎盘中检测到DTLR4的一种转录体，长度约为7.0kB。在卵巢和外周血单核细胞中观测到一种很弱的DTLR5信号，长度为4.0kB。
进化上比较古老的调节系统的组分利用基因组比较方法可以重建信号通路的原始分子蓝图和趋异方向。Miklos and Rubin(1996)Cell86521-529；Chothia(1994)Develop.1994 Suppl.，27-33；Banfi，et al.(1996)J.Biol.Chem.2714468-4476。我们利用该推理方法鉴定出一种新的人类基因家族，该家族目前编码5种类似的受体，即DTLRs1-5，这些受体是以Toll为代表的果蝇基因家族的直向进化对应物(图1-3)。人与果蝇DTLRs的结构保守性，包括保守的LRR胞外结构域和胞内TH区块(图1)，提示果蝇体内与Toll偶联的稳健通路也存在于脊椎动物体内。最好的证据则来自一种重复通路多种IL-1系统及其受体融合TH结构域库、IRAK、NF-κB和I-κB同源物(Belvin and Anderson(1996)Ann.Rev.Cell Develop.Biol.12393-416；Wasserman(1993)Molec.Biol.Cell4767-771；Hardiman，et al.(1996)Oncogene132467-2475；和Cao，et al.(1996)Science2711128-1131)；此外还鉴定出一种Tube样因子。目前还不清楚DTLRs是否能够与IL-IR信号通路有效偶联，也不清楚使用一组平行蛋白是否可行。据推测，人DTLRs与IL-1受体的不同之处在于其LRR架可保持对Sp_tzle/Trunk相关胱氨酸簇因子的亲和力；目前已分离出一些适用于该模型的候选DTLR配体(被称为PENs)。
利用在信号通路中相互作用的蛋白折叠的保守性可以对信号转导的生化机制进行判断。Miklos and Rubin(1996)Cell86521-529；Chothia(1994)Develop.1994 Suppl.，27-33。目前的Toll信号通路示意图中包含一些通过其结构、作用或结果来严密定义的分子Pelle是一种Ser/Thr激酶(磷酸化)，Dorsal是一种NF-κB样转录因子(与DNA结合)，Cactus是一种锚蛋白重复抑制因子(与Dorsal结合，降解)。Belvin and Anderson(1996)Ann.Rev.Cell Develop.Biol.12393-416。相比之下，Toll TH结构域和Tube的功能仍不清楚。与其它细胞因子受体相同(Heldin(1995)Cell80213-223)，配体介导的Toll二聚体形成可能是一种触发事件Toll近膜区的游离半胱氨酸可用于产生组成型活性受体对(Schneider，et al.(1991)Genes Develop.5797-807)，而Torso-Toll嵌合受体是以二聚体的形式发挥信号功能(Galindo，et al.(1995)Develop.1212209-2218)；但Toll胞外域的严重截断或全部丧失可导致胞内域的信号作用出现混乱(Norris and Manley(1995)Genes Develop.9358-369；和Winans and Hashimoto(1995)Molec.Biol.Cell6587-596)，这使人联想起带有催化结构域的癌基因受体(Heldin(1995)Cell80213-223)。Tube位于膜上，它能够与Pelle的N端(死亡)结构域结合，并且被磷酸化，但是用双杂交分析方法未能检测到Toll-Tube或Toll-Pelle相互作用(Galindo，et al.(1995)Develop.1212209-2218；和Gtoβhans，et al.(1994)Nature372563-566)；该结果说明Toll TH结构域的构象“状态”可通过某种方式对因子募集产生影响。Norris and Manley(1996)Genes Develop.10862-872；和Galindo，et al.(1995)Develop.1212209-2218。
在这些繁杂的问题中，最重要的是Toll TH组件的结构特性。为解决这个问题，我们根据昆虫、植物、脊椎动物以及人DTLR的TH序列的进化多样性提取出该保守蛋白的最小化核心，并将其用于结构预测和折叠识别(图2)。明显预测出的(β/α)5TH结构域折叠带有不对称的酸性残基簇，这种拓扑结构与细菌双组分通路中的应答调节因子相同(Volz(1993)Biochemistry3211741-11753；和Parkinson(1993)Cell73857-871)(图2A-2C)。典型的趋化调节因子CheY能够与核心β-片层C-末端的“天冬氨酸袋”中的二价阳离子短暂结合；该阳离子可提供静电稳定性，并且有利于激活恒定Asp的磷酸化。Volz(1993)Biochemistry3211741-11753。TH结构域的酸性套也能够俘获阳离子，但激活作用和随后的信号作用则依赖于特异性结合一种负电基团阴离子配体可陷落于精密的氢键网络，并以此来克服结合位点的强负电位。Ledvina，et al.(1996)Proc.Natl.Acad.Sci.USA936786-6791。令人感兴趣的是，在Tube/Pelle复合物与Toll的组装过程或植物和脊椎动物的类似系统中，TH结构域可能不只是作为被动支架，而是能作为真正的构象引发物主动参与信号转导系统。Toll二聚体形成可以通过调节性受体尾来促进其暴露(Norris and Manley(1995)Genes Develop.9358-369；Norrisand Manley(1996)Genes Develop.10862-872)，或通过TH袋的小分子激活物来促进其结合，这可能是Tube/Pelle复合物有条件结合的原因。但细胞内的“游离”TH组件(Norris and Manley(1995)Genes Develop.9358-369；Winans and Hashimoto(1995)Molec.Biol.Cell6587-596)可通过激活和结合游离的Tube/Pelle复合物来发挥其CheY样引发物的催化作用。
形态发生受体和免疫防御昆虫与脊椎动物免疫系统之间的进化关系被记录在DNA中昆虫抗微生物因子编码基因的上游基序与已知能结合NF-κB转录因子的哺乳动物体急性期应答因子相似。Hultmark(1993)Trends Genet.9178-183。被细菌攻击后，Dorsal和两种Dorsal相关因子Dif及Relish都有助于诱导这些防御蛋白产生(Reichhart，et al.(1993)C.R.Acad.Sci.Paris3161218-1224；Ip，et al.(1993)Cell75753-763；和Dushay，et al.(1996)Proc.Natl.Acad.Sci.USA9310343-10347)；Toll或其他DTLRs可能会调节成体果蝇中的这些快速免疫应答(Lemaitre，et al.(1996)Cell86973-983；和Rosetto.et al.(1995)Biochem.Biophys.Res.Commun.209111-116)。这些类似于脊椎动物IL-1炎症反应的机制可以证明Toll信号通路的功能多样性，并且表明胚胎模式形成和先天免疫之间存在古老的协同性(Belvin and Anderson(1996)Ann.Rev.Cell Develop.Biol.12393-416；Lemaitre，et al.(1996)Cell86973-983；Wasserman(1993)Molec.Biol.Cell4767-771；Wilson，et al.(1997)Curt.Biol.7175-178；Hultmark(1993)Trends Genet.9178-183；Reichhart，et al.(1993)C.R.Acad.Sci.Paris3161218-1224；Ip，et al.(1993)Cell 75753-763；Dushay，etal.(1996)Proc.Natl.Acad.Sci.USA9310343-10347；Rosetto，et al.(1995)Biochem.Biophys.Res.Commun.209111-116；Medzhitov and Janeway(1997)Curr.Opin.Immunol.94-9；和Medzhitov and Janeway(1997)Curr.Opin.Immunol.94-9)。昆虫和人的DTLR蛋白具有更高的同源性，因而在替换与IL-1系统类似的纯免疫系统方面，其生物学功能的重叠性也更强，并且可以在脊椎动物胚胎的背腹形成或其他变化中借用一些潜在的调节分子。DeRobertis and Sasai(1996)Nature38037-40；和Arendt andNübler-Jung(1997)Mech.Develop.617-21。
最近发现的脊椎动物Wnt模式形成因子Frizzled受体也反映在本文描述的新兴但稳健的人类受体家族中。Wang，et al.(1996)J.Biol.Chem.2714468-4476。由于在早期发育过程中有其他多种细胞因子-受体系统发挥作用(Lemaire and Kodjabachian(1996)Trends Genet.12525-531)，因而致密胚胎与细长成体的不同细胞环境可能是导致类似信号通路及其扩散性引发物，如形态发生和免疫防御中的DTLR，在不同时间产生不同生物学效应的简单原因。对昆虫、植物和人的Toll相关系统而言(Hardiman，et al.(1996)Oncogene132467-2475；Wilson，et al.(1997)Curr.Biol.7175-178)，这些信号要经过调节性TH结构域，令人感兴趣的是，该TH结构域类似于细菌的转导系统(Parkinson(1993)Cell73857-871)。
具体地说，DTLR6具有使其成为该家族成员的结构特性。此外，该家族的成员可能涉及多种主要的发育疾病，并且可参与先天免疫系统的功能。详细地说，DTLR6定位于X染色体，其位置是用于研究主要发育异常疾病的热点。例如可参考Sanger中心人类X染色体网站http://www.sanger.ac.uk/HGP/ChrX/index.shtml；以及Baylor医学院人类基因组测序网站http://gc.bcm.tmc.edu8088/cgi-bin/seq/home。
保存的PAC的登录号为AC003046。该登录号包括两种PACs的序列RPC-164K3和RPC-263P4。这两种PAC序列定位于人染色体Xp22，在Baylor网站中是定位于STS标记DXS704和DXS7166之间。该区域是用于研究几种发育异常疾病的“热点”。
III.DTLR片段的PCR扩增选择两种适当的引物序列(见表1-10)。选择含有适当信息的mRNA样品，如能够表达特定基因的样品，进行RT-PCR以产生部分或全长cDNA。可参考，例如，Innis，et al.(1990年版)《PCR实验方法及应用指南》Academic Press，San Diego，CA和Dieffenbachand Dveksler(1995年版)《PCR引物实验手册》Cold Spring HarborPress，CSH，NY。由此来确定适用于在cDNA库中探测全长基因的序列。基因组中的DTLR6序列是连续的，其他DTLRs可能也是如此。因而对基因组DNA进行PCR可能会产生连续的全长序列，然后可以使用染色体步查法。作为选择，序列库中可含有与所述实施方案的某些部分相关的序列或其密切相关的形式，如可变剪接形式，等等。此外，还可以将表达克隆技术应用于cDNA库。
IV.DTLRs的组织分布目前已获得了这些DTLRs的每种编码基因的信息。参考图5A-5F。对其他细胞和组织的检测可采用适当的技术，如PCR、免疫测定、杂交，等等。组织和器官的cDNA制品可由Clontech，Mountain View，CA等公司购买。按文中所述对天然表达源进行检测的方法也同样适用。
DNA印迹分析用适当的限制酶对来源于灵长类动物扩增cDNA库的DNA(5μg)进行消化，以释放其插入序列，用1％琼脂糖凝胶进行电泳，然后转移到尼龙膜上(Schleicher and Schuell，Keene，NH)。
用于分离人mRNA的样品通常包括，例如外周血单核细胞(单核细胞、T细胞、NK细胞、粒细胞、B细胞)，静息型(T100)；外周血单核细胞，用抗CD3活化2、6、12小时后收集(T101)；T细胞，TH0克隆Mot 72，静息型(T102)；T细胞，TH0克隆Mot 72，用抗CD28和抗CD3活化3、6、12小时后收集(T103)；T细胞，TH0克隆Mot 72，用特定的肽无反应性处理2、7、12小时后收集(T104)；T细胞，TH1克隆HY06，静息型(T107)；T细胞，TH1克隆HY06，用抗CD28和抗CD3活化3、6、12小时后收集(T108)；T细胞，TH1克隆HY06，用特定的肽无反应性处理2、6、12小时后收集(T109)；T细胞，TH2克隆HY935，静息型(T110)；T细胞，TH2克隆HY935，用抗CD28和抗CD3活化2、7、12小时后收集(T111)；T细胞，在抗CD28、IL-4和抗IFN-γ中极化27天的CD4+CD45RO-T细胞，用抗CD3和抗CD28活化4小时至极化TH2(T116)；Jurkat和Hut78肿瘤T细胞系，静息型(T117)；T细胞克隆，合并的AD130.2、Tc783.12、Tc783.13、Tc783.58、Tc782.69，静息型(T118)；T细胞，随机γδT细胞克隆，静息型(T119)；脾细胞，静息型(B100)；脾细胞，用抗CD40和IL-4活化(B101)；EBV系B细胞，合并的WT49、RSB、JY、CVIR、721.221、RM3、HSY，静息型(B102)；JY系B细胞，用PMA和离子霉素活化1、6小时后收集(B103)；合并的NK20克隆，静息型(K100)；合并的NK20克隆，用PMA和离子霉素活化6小时(K101)；NKL克隆，来自LGL白血病患者的外周血，IL-2处理(K106)；NK细胞毒性克隆640-A30-1，静息型(K107)；TF1系造血细胞前体，用PMA和离子霉素活化1、6小时后收集(C100)；U937前单核细胞系，静息型(M100)；U937前单核细胞系，用PMA和离子霉素活化1、6小时后收集(M101)；净化的单核细胞，用LPS、IFNγ、抗IL-10活化1、2、6、12、24小时后收集(M102)；净化的单核细胞，用LPS、IFNγ、IL-10活化1、2、6、12、24小时后收集(M103)；净化的单核细胞，用LPS、IFNγ、抗IL-10活化4、16小时后收集(M106)；净化的单核细胞，用LPS、IFNγ、IL-10活化4、16小时后收集(M107)；净化的单核细胞，用LPS活化1小时(M108)；净化的单核细胞，用LPS活化6小时(M109)；DC 70％CD1a+，来自CD34+GM-CSF，TNFα处理12天，静息型(D101)；DC 70％CD1a+，来自CD34+GM-CSF，TNFα处理12天，用PMA和离子霉素活化1小时(D102)；DC 70％CD1a+，来自CD 34+GM-CSF，TNFα处理12天，用PMA和离子霉素活化6小时(D103)；DC 95％CD1a+，来自CD34+GM-CSF，TNFα处理12天后FACS分类，用PMA和离子霉素活化1、6小时后收集(D104)；DC 95％CD14+，不含CD34+GM-CSF，TNFα处理12天后FACS分类，用PMA和离子霉素活化1、6小时后收集(D105)；DC CD1a+CD86+，来自CD34+GM-CSF，TNFα处理12天后FACS分类，用PMA和离子霉素活化1、6小时后收集(D106)；来自单核细胞GM-CSF的DC，IL-4处理5天，静息型(D107)；来自单核细胞GM-CSF的DC，IL-4处理5天，静息型(D108)；来自单核细胞GM-CSF的DC，IL-4处理5天，用LPS活化4、16小时后收集(D109)；来自单核细胞GM-CSF的DC，IL-4处理5天，用TNFα、单核细胞上清液活化4、16小时后收集(D110)；平滑肌瘤L11良性肿瘤(X101)；正常子宫肌层M5(0115)；恶性平滑肌肉瘤GS1(X103)；MRC5系肺纤维母细胞瘤，用PMA和离子霉素活化1、6小时后收集(C101)；CHA系肾上皮癌细胞，用PMA和离子霉素活化1、6小时后收集(C102)；28周男性胎肾(0100)；28周男性胎肺(0101)；28周男性胎肝(0102)；28周男性胎心(0103)；28周男性胎脑(0104)；28周男性胎儿胆囊(0106)；28周男性胎儿小肠(0107)；28周男性胎儿脂肪组织(0108)；25周女性胎儿卵巢(0109)；25周女性胎儿子宫(0110)；28周男性胎儿睾丸(0111)；28周男性胎脾(0112)；28周成熟胎盘(0113)；以及发炎的扁桃体，来自12岁的个体(X100)。
用于分离小鼠mRNA的样品包括，例如静息的小鼠成纤维细胞L细胞系(C200)；BrafER(Braf与雌激素受体的融合体)转染的细胞，对照；T细胞，TH1极化(来自脾的Me114幼CD4+细胞，用IFN-γ和抗IL-4极化7天；T200)；T细胞，TH2极化(来自脾的Me114幼CD4+细胞，用IL-4和抗IFN-γ极化7天；T201)；T细胞，TH1高度极化(参考Openshaw，et al.(1995)J.Exp.Med.1821357-1367；用抗CI-3活化2、6、16小时后收集；T202)；T细胞，TH2高度极化(参考Openshaw，et al.(1995)J.Exp.Med.1821357-1367；用抗CD-3活化2、6、16小时后收集；T203)；CD44-CD25+前T细胞，从胸腺中分类获得(T204)；TH1 T细胞克隆D1.1，在最后一次抗原刺激之后静息3周(T205)；TH1 T细胞克隆D1.1，用10μg/mlConA刺激15小时(T206)；TH2 T细胞克隆CDC35，在最后一次抗原刺激之后静息3周(T207)；TH2 T细胞克隆CDC35，用10μg/mlConA刺激15小时(T208)；来自脾的Me114+幼T细胞，静息型(T209)；Me114+T细胞，用IFN-γ/IL12/抗IL-4极化6、12、24小时至TH1后收集(T210)；Me114+T细胞，用IL-4/抗IFN-γ极化6、13、24小时至TH2后收集(T211)；未经刺激的成熟B细胞白血病A20细胞系(B200)；未经刺激的CH12系B细胞(B201)；未经刺激的脾大B细胞(B202)；整个脾的B细胞，LPS活化(B203)；经三碘苯甲酰氨基葡糖富集的脾树突状细胞，静息型(D200)；骨髓树突状细胞，静息型(D201)；单核细胞RAW264.7细胞系，用LPS活化4小时(M200)；来自GM和M-CSF的骨髓巨噬细胞(M201)；巨噬细胞J774细胞系，静息型(M202)；巨噬细胞J774细胞系，用LPS和抗IL-10处理0.5、1、3、6、12小时后收集(M203)；巨噬细胞J774细胞系，用LPS和IL-10处理0.5、1、3、5、12小时后收集(M203)；气雾剂诱发的小鼠肺组织，Th2致敏，用气雾剂OVA诱发7、14、23小时后收集(参考Garlisi，et al.(1995)临床免疫学和免疫病理学，7575-83；X206)；日本圆线虫感染的肺组织(参考Coffman，etal.(1989)Science245308-310；X200)；正常的成熟全肺(0200)；全肺，rag-1(参考Schwarz，et al.(1993)Immunodeficiency4249-252；0205)；经IL-10处理的脾(参考Kuhn，et al.(1991)Cell 75263-274；X201)；正常的成熟全脾(0201)；全脾，rag-1(0207)；经IL-10处理的派尔集合淋巴结(0202)；正常的全派尔集合淋巴结(0210)；经IL-10处理的肠系膜淋巴结(X203)；正常的总肠系膜淋巴结(0211)；经IL-10处理的结肠(X203)；正常全结肠(0212)；NOD小鼠胰腺(参考Makino，et al.(1980)JikkenDobutsu291-13；X205)；全胸腺，rag-1(0208)；全肾，rag-1(0209)；全心脏，rag-1(0202)；全脑，rag-1(0203)；全睾丸，rag-1(0204)；全肝脏，rag-1(0206)；大鼠正常关节组织(0300)；和大鼠关节炎性关节组织(X300)。
检测发现，DTLR10能够在2型前树突状细胞(pDC2)中高水平表达。可参考，例如，Rissoan，et al.(1999)Science2831183-1186；和Siegal，et al.(1999)Science2841835-1837。但在单核细胞中不表达。DTLR10的局限性表达进一步表明其在宿主免疫防御中的受体作用。pDC 2细胞是天然的产干扰素细胞(NIPC)，它可以在对单纯疱疹病毒感染的应答过程中产生大量的IFNα。
V.DTLRs物种对应物的克隆方法可使用多种策略来获得这些DTLRs的物种对应物，优选的是来源于其他灵长类动物。一种方法是利用近亲物种的DNA特征进行杂交。它可作为对进化上相似的物种进行研究的有效中间步骤。另一种方法是使用特定的PCR引物，该方法的基础是要确定人类等特定物种的基因之间的相似部分或差异部分，如高度保守或非保守的多肽或核苷酸序列区域。作为选择，还可将抗体用于表达克隆化。
VI.哺乳动物DTLR蛋白的产生设计一种适当的融合构建体，如GST融合构建体，用于，例如，在大肠杆菌中表达。举例来说，可以构建一种小鼠IGIF pGex质粒，并将其转化到大肠杆菌中。将新转化的细胞培养在含有50μg/ml氨苄青霉素的LB培养基中，并用IPTG(Sigma，St.Louis，MO)进行诱导。诱导过夜，然后收集细菌，并分离出含有DTLR蛋白的沉淀。用2升TE缓冲液(50mM Tris-base pH8.0、10mM EDTA和2mMpefabloc)使沉淀匀浆。使该匀浆液3次穿过微量流化器(Microfluidics，Newton，MA)。用Sorval GS-3转头使流化上清13,000rpm离心1小时。将获得的含有DTLR蛋白的上清液过滤，并使其穿过在50mM Tris-base pH8.0中平衡的谷胱甘肽-SEPHAROSE柱。将含有DTLR-GST融合蛋白的组分合并，然后用凝血酶(EnzymeResearch Laboratories，Inc.，South Bend，IN)剪切。然后使剪切的合并物穿过50mM Tris-base平衡的Q-SEPHAROSE柱。将含有DTLR的组分合并，再用冷蒸馏水稀释，以降低其传导率，然后只需再次穿过新平衡的Q-Sepharose柱，或是接着再穿过一种免疫亲和抗体柱。将含有DTLR蛋白的组分合并，分装，并保存于-70℃冰箱。
DTLR1蛋白的CD谱比较结果说明该蛋白已正确折叠。可参考Hazuda，et al.(1969)J.Biol.Chem.2641689-1693。
VII.用DTLRs进行生物学测定生物学测定通常涉及蛋白的配体结合特性或受体的激酶/磷酸酶活性。与其他多种酶的作用相同，受体的这种活性通常是可逆的，并且可调节磷酸酶或磷酸化酶的活性，这些活性可通过标准方法来方便地检测。可参考，例如，Hardie，et al.(1995年版)《蛋白激酶手册》第I和第II卷，Academic Press，San Diego，CA；Hanks，etal.(1991)Meth.Enzymol.20038-62；Hunter，et al.(1992)Cell70375-388；Lewin(1990)Cell61743-752；Pines，et al.(1991)Cold Spring Harbor Symp.Quant.Biol.56449-463；和Parker，et al.(1993)Nature363736-738。
白介素1s家族包括一些可作为炎症疾病重要介体的分子。有关的综合论述，可参考Dinarello(1996)“白介素-1在疾病中的生物学基础”Blood872095-2147。有人认为，可能有多种Toll配体在疾病初期发挥着重要作用，特别是炎症反应初期。与IL-1家族有关的新蛋白的发现有助于鉴定那些可作为疾病初期主要成分的分子，并且有助于产生范围更广、疗效更高的治疗策略。
VIII.诸如DTLR4的特异性抗体的制备用纯化DTLR4等重组蛋白或稳定转染的NIH-3T3细胞对近交Ba1b/c小鼠进行腹膜内免疫。在适当时间点用附加或不加佐剂的蛋白对动物进行再次注射促升，以进一步刺激抗体的产生。收集血清，或收集脾中产生的杂交瘤细胞。
作为选择，还可以用该基因或其片段转化的内源性或外源性细胞对Balb/c小鼠进行免疫，也可以用分离的抗原富集膜对Ba1b/c小鼠进行免疫。在适当的时间收集血清，一般是在多次给药之后收集血清。为了产生免疫应答，可以用多种基因治疗技术来实现，例如，原位蛋白产生。
可以制备单克隆抗体。例如将脾细胞与适当的融合配偶体相融合，并利用标准方法在生长培养基中挑选杂交瘤细胞。利用诸如ELISA或其他测定方法筛选那些含有能够与所需DTLR结合的抗体的杂交瘤细胞上清液。还可以选择或制备能够特异性识别特定DTLR的抗体。
用于产生单克隆或多克隆抗体的另一种方法是将合成肽或纯化蛋白呈递至免疫系统。可参考，例如，Coligan(1991)《最新免疫学实验方法》Wiley/Greene；和Harlow and Lane(1989)《抗体实验手册》Cold Spring Harbor Press。在适当条件下，可以按上文所述对结合剂进行标记，如荧光标记等，也可以将结合剂固定在一种基质上，以便在淘选方法中使用。还可以将核酸引入动物体内的细胞，以产生用于诱导免疫应答的抗原。可参考，例如，Wang，et al.(1993)Proc.Nat’l.Acad.Sci.904156-4160；Barry，et al.(1994)BioTechniques 16616-619；和Xiang，et al.(1995)Immunity2129-135。
IX.诸如DTLR5的融合蛋白的产生用DTLR5可以制备多种融合构建体。可以将该基因部分与FLAG等表位标记相融合，也可以与一种双杂交系统构建体相融合。可参考，例如，Fields and Song(1989)Nature340245-246。
该表位标记可以在表达克隆化过程中使用，以便于利用抗-FLAG抗体来检测结合配偶体，如相应DTLR5的配体。也可以用双杂交系统来分离与DTLR5特异性结合的蛋白。
X.DTLRs的染色体制图制备铺展染色体。在用培养72小时并经植物凝集素刺激的淋巴细胞制备的铺展染色体上进行原位杂交。在最后7个小时的培养过程中添加5-溴脱氧尿嘧啶，以确保杂交后染色体能够良好地显带。
以B细胞总cDNA为模板，用引物扩增出适当的片段，如PCR片段，然后将该片段克隆到适当的载体中。利用3H缺口平移技术对该载体进行标记。按Mattei，et al.(1985)Hum.Genet.69327-331中的描述使标记探针与中期铺展染色体杂交。
用核径迹乳剂(KODAK NTB2)包被玻片，并使其曝光，例如，4℃曝光18天。为避免银颗粒在显带过程中移动，首先用Giemsa缓冲溶液对铺展染色体染色，并进行中期照相。然后用荧光染料-光解-Giemsa(FPG)法进行R-显带操作，中期照相，并进行分析。
作为选择，还可以按上文所述进行FISH。DTLR基因位于不同的染色体上。DTLR2和DTLR3定位于人类第4号染色体；DTLR4定位于人类第9号染色体，而DTLR5定位于人类第1号染色体。参考图4A-4D。
XI.结构活性关系利用标准的程序和分析方法来确定特定残基的关键程度。实施标准诱变分析的方法是，例如，在预定位点，如上文确定的位点，产生多种不同的变体，并评定这些变体的生物活性。利用该方法可以最终确定那些可以改变活性的位点，也可以针对特定的位置来确定那些被取代后能够保留、阻断或调节生物活性的残基。
作为选择，对天然变体进行分析的结果可以表明那些能够耐受天然突变的位点。这可以通过对个体或杂交品系或物种的种群变异分析来实现。对选定的个体样品进行分析的方法可以是，例如，PCR分析和测序。由此可以对种群多态性进行评定。
XI.DTLR配体的分离利用DTLR的结合特异性可将其作为特异性结合剂来鉴定其结合配偶体，这非常类似于使用。可以如上所述对结合剂进行标记，如荧光标记等，也可以将其固定在一种基质上，以便在淘选方法中使用。
该结合组合物可用于筛选由一种细胞系制备的表达库，该细胞系可以表达一种结合配偶体，即配体，优选的是与膜结合的配体。利用标准的染色技术对表面表达的配体进行检测或分类，或用淘选方法对表面表达转化细胞进行筛选。胞内表达的筛选可通过多种染色或免疫荧光方法来实现。还可参考McMahan，et al.(1991)EMBO J.102821-2832。
举例来说，第0天，用10ng/ml溶于PBS的纤连蛋白对双池玻片进行预包被，每池使用1ml，室温预包被30分钟。PBS洗涤一次。然后将COS细胞铺片，每池使用1.5ml生长培养基，其中含有2-3×105个细胞。37℃保温过夜。
第一天，制备含有66μg/ml DEAE-葡聚糖、66μM氯奎和4μg DNA的无血清DME溶液，每种样品制备0.5ml。每组样品制备一个阳性对照，如稀释度为1和1/200的DTLR-FLAG cDNA，并制备一个阴性对照。用无血清DME洗涤细胞。添加DNA溶液，并于37℃保温5小时。去除培养基，并添加0.5ml溶于DME的10％DMSO，作用2.5分钟。去除并用DME洗涤一次。添加1.5ml生长培养基并保温过夜。
第二天，改变培养基。第三天或第四天，固定细胞并染色。用Hank’s缓冲盐溶液(HBSS)将细胞洗涤两次，再用4％多聚甲醛(PFA)/葡糖将细胞固定5分钟。然后用HBSS将细胞洗涤三次。去除所有液体，然后将玻片保存于-80℃。按下述方法进行保温，每池使用0.5ml。添加含有32μl/ml 1M叠氮化钠的HBSS/皂角苷(0.1％)，保温20分钟。然后用HBSS/皂角苷将细胞洗涤一次。在细胞中添加适当的DTLR或DTLR/抗体复合物，保温30分钟。再用HBSS/皂角苷将细胞洗涤两次。在适当条件下可以先添加抗体并保温30分钟。再添加稀释度为1/200的二抗，如Vector抗小鼠抗体，并保温30分钟。制备ELISA溶液，如Vector Elite ABC辣根过氧化物酶溶液，并预保温30分钟。每2.5ml HBSS/皂角苷使用，例如，1滴溶液A(抗生物素蛋白)和1滴溶液B(生物素)。用HBSS/皂角苷将细胞洗涤两次。添加ABC HRP溶液并保温30分钟。用HBSS将细胞洗涤两次，第二次洗2分钟，以封闭细胞，然后添加Vector二氨基联苯胺(DAB)，保温5-10分钟。每5ml蒸馏水中添加2滴缓冲液、4滴DAB和2滴双氧水。仔细移去样品池，并将玻片置水中洗涤。空气干燥数分钟，然后添加1滴Crystal Mount和盖玻片。85-90℃烘焙5分钟。
鉴定阳性染色样品池，然后逐步进行亚克隆，以分离能够结合的单个基因。
作为选择，还可以用DTLR试剂来亲和纯化或分选能够表达假定配体的细胞。可参考，例如，Sambrool，et al.或Ausubel，et al.。
另一种策略是用淘选方法筛选与膜结合的受体。如上所述构建受体cDNA。可以将配体固定化，并用于固定表达细胞。可以用能够识别诸如DTLR融合构建体中的FLAG序列的适当抗体来进行固定，也可以利用由一抗产生的抗体来实现固定。通过循环筛选和扩增即可实现适当克隆的富集，并且最终分离出受体表达克隆。
还可以用哺乳动物DTLRs对噬菌体表达库进行筛选。利用适当的标记技术，如抗-FLAG抗体，可以特异性地标记适当克隆。
文中的所有引文均以相同的程度在此引入作为参考，其方式就如同每个出版物或专利申请都单独地特别指明被引入作为参考。
该领域的技术人员都了解，在不脱离本发明的精神和范围的情况下，本发明可以有多种修改和变化。文中描述的特定实施方案只作为实例加以提供，而本发明将局限于附属权利要求的条款，以及与这些权利要求的授权相同的整个范围；本发明并不局限于文中以实例方式提供的特定实施方案。
人类具有两种不同类型的树突状细胞(DC)前体。经GMCSF和IL-4培养之后的外周血单核细胞(pDC1)可形成未成熟的髓样DCs。经CD40配体(CD40L)刺激之后，这些未成熟细胞可变为成熟的髓样DCs(DC1)。经IL-3培养之后，来自血液或扁桃体的CD4+CD3-CD11c-浆细胞样细胞(pDC2)可形成不同类型的未成熟DC，经CD40L刺激后可分化为成熟的DCs(DC2)。Rissoan，et al.(1999)Science2831183-1186。
根据Siegal，et al.(1999)Science2841835-1837的描述，pDC2是“天然的产干扰素细胞”(IPC)。干扰素(IFNs)是抗病毒免疫应答中最重要的细胞因子。人类血液中的“天然产干扰素细胞”(NIPCs)可表达CD4和II-类主要组织相容性复合体蛋白，但由于这些细胞很稀少，并且会迅速凋亡，同时又缺乏同系标记物，所以至今还未能对其进行分离和进一步检测。本文的纯化NIPCs是CD4(+)CD11c-2型树突状细胞前体(pDC2s)，被微生物诱发后，该细胞能产生比其他血细胞多200-1000倍的IFN。因此，pDC2s是一类免疫系统效应细胞，它在抗病毒和抗肿瘤免疫应答中起着关键作用。这些细胞被认为是HIV感染患者内的重要细胞。
Toll-样受体(TLR)分子属于IL-1/Toll受体家族。目前已鉴定出TLR2和TLR4的配体，这些配体的功能与宿主对微生物抗原或损伤的免疫应答有关。Takeuchi，et al.(1999)Immunity11443-451；和Noshino，et al.(1999)J.Immunol.1623749-3752。TLRs的表达模式可能是限制性的。Muzio，et al.(2000)J.Immunol.1645998-6004。这些结果说明i)TLR10能够在pDC2s中高水平表达，并且其表达局限于pDC2s，以及ii)pDC2属于NIPC，TLR10可能在宿主先天免疫应答中起着重要作用。
序列表SEQ ID NO1提供灵长类动物的DTLR1核苷酸序列。
SEQ ID NO2提供灵长类动物的DTLR1多肽序列。
SEQ ID NO3提供灵长类动物的DTLR2核苷酸序列。
SEQ ID NO4提供灵长类动物的DTLR2多肽序列。
SEQ ID NO5提供灵长类动物的DTLR3核苷酸序列。
SEQ ID NO6提供灵长类动物的DTLR3多肽序列。
SEQ ID NO7提供灵长类动物的DTLR4核苷酸序列。
SEQ ID NO8提供灵长类动物的DTLR4多肽序列。
SEQ ID NO9提供灵长类动物的DTLR5核苷酸序列。
SEQ ID NO10提供灵长类动物的DTLR5多肽序列。
SEQ ID NO11提供灵长类动物的DTLR6核苷酸序列。
SEQ ID NO12提供灵长类动物的DTLR6多肽序列。
SEQ ID NO13提供啮齿类动物的DTLR6核苷酸序列。
SEQ ID NO14提供啮齿类动物的DTLR6多肽序列。
SEQ ID NO15提供灵长类动物的DTLR7核苷酸序列。
SEQ ID NO16提供灵长类动物的DTLR7多肽序列。
SEQ ID NO17提供灵长类动物的DTLR7核苷酸序列。
SEQ ID NO18提供灵长类动物的DTLR7多肽序列。
SEQ ID NO19提供灵长类动物的DTLR8核苷酸序列。
SEQ ID NO20提供灵长类动物的DTLR8多肽序列。
SEQ ID NO21提供灵长类动物的DTLR9核苷酸序列。
SEQ ID NO22提供灵长类动物的DTLR9多肽序列。
SEQ ID NO23提供灵长类动物的DTLR10核苷酸序列。
SEQ ID NO24提供灵长类动物的DTLR10多肽序列。
SEQ ID NO25提供灵长类动物的DTLR4核苷酸序列。
SEQ ID NO26提供灵长类动物的DTLR4多肽序列。
SEQ ID NO27提供啮齿类动物的DTLR6核苷酸序列。
SEQ ID NO28提供啮齿类动物的DTLR6多肽序列。
SEQ ID NO29提供啮齿类动物的DTLR6核苷酸序列。
SEQ ID NO30提供啮齿类动物的DTLR6多肽序列。
SEQ ID NO31提供灵长类动物的DTLR8核苷酸序列。
SEQ ID NO32提供灵长类动物的DTLR8多肽序列。
SEQ ID NO33提供灵长类动物的DTLR10核苷酸序列。
SEQ ID NO34提供灵长类动物的DTLR10多肽序列。
SEQ ID NO35提供啮齿类动物的DTLR10核苷酸序列。
SEQ ID NO36提供灵长类动物的DTLR7核苷酸序列。
SEQ ID NO37提供灵长类动物的DTLR7多肽序列。
SEQ ID NO38提供灵长类动物的DTLR8核苷酸序列。
SEQ ID NO39提供灵长类动物的DTLR8多肽序列。
SEQ ID NO40提供灵长类动物的DTLR9核苷酸序列。
SEQ ID NO41提供灵长类动物的DTLR9多肽序列。
SEQ ID NO42提供灵长类动物的DTLR10核苷酸序列。
SEQ ID NO43提供灵长类动物的DTLR10多肽序列。
SEQ ID NO42提供啮齿类动物的DTLR10核苷酸序列。
SEQ ID NO43提供啮齿类动物的DTLR10多肽序列。
<110>先灵公司
<120>人受体蛋白；相关的试剂和方法<130>DX0724XKP<140>
<141>
<160>45<170>PatentIn Ver.2.0<210>1<211>2367<212>DNA<213>未知<220>
<223>未知生物的说明灵长类动物；推测为人(Homo sapiens)<220>
<221>CDS<222>(1)..(2358)<220>
<221>mat肽<222>(67)..(2358)<400>1atg act agc atc ttc cat ttt gcc att atc ttc atg tta ata ctt cag 48Met Thr Ser Ile Phe His Phe Ala Ile Ile Phe Met Leu Ile Leu Gln-20 -15 -10atc aga ata caa tta tct gaa gaa agt gaa ttt tta gtt gat agg tca 96Ile Arg Ile Gln Leu Ser Glu Glu Ser Glu Phe Leu Val Asp Arg Ser-5 -1 1 5 10aaa aac ggt ctc atc cac gtt cct aaa gac cta tcc cag aaa aca aca144Lys Asn Gly Leu Ile His Val Pro Lys Asp Leu Ser Gln Lys Thr Thr15 20 25atc tta aat ata tcg caa aat tat ata tct gag ctt tgg act tct gac192Ile Leu Asn Ile Ser Gln Asn Tyr Ile Ser Glu Leu Trp Thr Ser Asp30 35 40atc tta tca ctg tca aaa ctg agg att ttg ata att tct cat aat aga240Ile Leu Ser Leu Ser Lys Leu Arg Ile Leu Ile Ile Ser His Asn Arg45 50 55atc cag tat ctt gat atc agt gtt ttc aaa ttc aac cag gaa ttg gaa288Ile Gln Tyr Leu Asp Ile Ser Val Phe Lys Phe Asn Gln Glu Leu Glu60 65 70tac ttg gat ttg tcc cac aac aag ttg gtg aag att tct tgc cac cct336Tyr Leu Asp Leu Ser His Asn Lys Leu Val Lys Ile Ser Cys His Pro75 80 85 90
act gtg aac ctc aag cac ttg gac ctg tca ttt aat gca ttt gat gcc384Thr Val Asn Leu Lys His Leu Asp Leu Ser Phe Asn Ala Phe Asp Ala95 100 105ctg cct ata tgc aaa gag ttt ggc aat atg tct caa cta aaa ttt ctg432Leu Pro Ile Cys Lys Glu Phe Gly Asn Met Ser Gln Leu Lys Phe Leu110 115 120ggg ttg agc acc aca cac tta gaa aaa tct agt gtg ctg cca att gct480Gly Leu Ser Thr Thr His Leu Glu Lys Ser Ser Val Leu Pro Ile Ala125 130 135cat ttg aat atc agc aag gtc ttg ctg gtc tta gga gag act tat ggg528His Leu Asn Ile Ser Lys Val Leu Leu Val Leu Gly Glu Thr Tyr Gly140 145 150gaa aaa gaa gac cct gag ggc ctt caa gac ttt aac act gag agt ctg576Glu Lys Glu Asp Pro Glu Gly Leu Gln Asp Phe Asn Thr Glu Ser Leu155 160 165 170cac att gtg ttc ccc aca aac aaa gaa ttc cat ttt att ttg gat gtg624His Ile Val Phe Pro Thr Asn Lys Glu Phe His Phe Ile Leu Asp Val175 180 185tca gtc aag act gta gca aat ctg gaa cta tct aat atc aaa tgt gtg672Ser Val Lys Thr Val Ala Asn Leu Glu Leu Ser Asn Ile Lys Cys Val190 195 200cta gaa gat aac aaa tgt tct tac ttc cta agt att ctg gcg aaa ctt720Leu Glu Asp Asn Lys Cys Ser Tyr Phe Leu Ser Ile Leu Ala Lys Leu205 210 215caa aca aat cca aag tta tca agt ctt acc tta aac aac att gaa aca768Gln Thr Asn Pro Lys Leu Ser Ser Leu Thr Leu Asn Asn Ile Glu Thr220 225 230act tgg aat tct ttc att agg atc ctc caa cta gtt tgg cat aca act816Thr Trp Asn Ser Phe Ile Arg Ile Leu Gln Leu Val Trp His Thr Thr235240 245 250gta tgg tat ttc tca att tca aac gtg aag cta cag ggt cag ctg gac864Val Trp Tyr Phe Ser Ile Ser Asn Val Lys Leu Gln Gly Gln Leu Asp255 260 265ttc aga gat ttt gat tat tct ggc act tcc ttg aag gcc ttg tct ata912Phe Arg Asp Phe Asp Tyr Ser Gly Thr Ser Leu Lys Ala Leu Ser Ile270 275 280cac caa gtt gtc agc gat gtg ttc ggt ttt ccg caa agt tat atc tat960His Gln Val Val Ser Asp Val Phe Gly Phe Pro Gln Ser Tyr Ile Tyr285 290 295gaa atc ttt tcg aat atg aac atc aaa aat ttc aca gtg tct ggt aca 1008Glu Ile Phe Ser Asn Met Asn Ile Lys Asn Phe Thr Val Ser Gly Thr300 305 310
cgc atg gtc cac atg ctt tgc cca tcc aaa att agc ccg ttc ctg cat1056Arg Met Val His Met Leu Cys Pro Ser Lys Ile Ser Pro Phe Leu His315 320 325 330ttg gat ttt tcc aat aat ctc tta aca gac acg gtt ttt gaa aat tgt1104Leu Asp Phe Ser Asn Asn Leu Leu Thr Asp Thr Val Phe Glu Asn Cys335 340345ggg cac ctt act gag ttg gag aca ctt att tta caa atg aat caa tta1152Gly His Leu Thr Glu Leu Glu Thr Leu Ile Leu Gln Met Asn Gln Leu350 355 360aaa gaa ctt tca aaa ata gct gaa atg act aca cag atg aag tct ctg1200Lys Glu Leu Ser Lys Ile Ala Glu Met Thr Thr Gln Met Lys Ser Leu365 370 375caa caa ttg gat att agc cag aat tct gta agc tat gat gaa aag aaa1248Gln Gln Leu Asp Ile Ser Gln Asn Ser Val Ser Tyr Asp Glu Lys Lys380 385 390gga gac tgt tct tgg act aaa agt tta tta agt tta aat atg tct tca1296Gly Asp Cys Ser Trp Thr Lys Ser Leu Leu Ser Leu Asn Met Ser Ser395 400 405 410aat ata ctt act gac act att ttc aga tgt tta cct ccc agg atc aag1344Asn Ile Leu Thr Asp Thr Ile Phe Arg Cys Leu Pro Pro Arg Ile Lys415 420 425gta ctt gat ctt cac agc aat aaa ata aag agc att cct aaa caa gtc1392Val Leu Asp Leu His Ser Asn Lys Ile Lys Ser Ile Pro Lys Gln Val430 435 440gta aaa ctg gaa gct ttg caa gaa ctc aat gtt gct ttc aat tct tta1440Val Lys Leu Glu Ala Leu Gln Glu Leu Asn Val Ala Phe Asn Ser Leu445 450 455act gac ctt cct gga tgt ggc agc ttt agc agc ctt tct gta ttg atc1488Thr Asp Leu Pro Gly Cys Gly Ser Phe Ser Ser Leu Ser Val Leu Ile460 465 470att gat cac aat tca gtt tcc cac cca tca gct gat ttc ttc cag agc1536Ile Asp His Asn Ser Val Ser His Pro Ser Ala Asp Phe Phe Gln Ser475 480 485 490tgc cag aag atg agg tca ata aaa gca ggg gac aat cca ttc caa tgt1584Cys Gln Lys Met Arg Ser Ile Lys Ala Gly Asp Asn Pro Phe Gln Cys495 500 505acc tgt gag ctc gga gaa ttt gtc aaa aat ata gac caa gta tca agt1632Thr Cys Glu Leu Gly Glu Phe Val Lys Asn Ile Asp Gln Val Ser Ser510 515 520gaa gtg tta gag ggc tgg cct gat tct tat aag tgt gac tac ccg gaa1680Glu Val Leu Glu Gly Trp Pro Asp Ser Tyr Lys Cys Asp Tyr Pro Glu525 530 535agt tat aga gga acc cta cta aag gac ttt cac atg tct gaa tta tcc1728
Ser Tyr Arg Gly Thr Leu Leu Lys Asp Phe His Met Ser Glu Leu Ser540 545 550tgc aac ata act ctg ctg atc gtc acc atc gtt gcc acc atg ctg gtg1776Cys Asn Ile Thr Leu Leu Ile Val Thr Ile Val Ala Thr Met Leu Val555 560 565 570ttg gct gtg act gtg acc tcc ctc tgc atc tac ttg gat ctg ccc tgg1824Leu Ala Val Thr Val Thr Ser Leu Cys Ile Tyr Leu Asp Leu Pro Trp575 580 585tat ctc agg atg gtg tgc cag tgg acc cag acc cgg cgc agg gcc agg1872Tyr Leu Arg Met Val Cys Gln Trp Thr Gln Thr Arg Arg Arg Ala Arg590 595 600aac ata ccc tta gaa gaa ctc caa aga aat ctc cag ttt cat gca ttt1920Asn Ile Pro Leu Glu Glu Leu Gln Arg Asn Leu Gln Phe His Ala Phe605 610 615att tca tat agt ggg cac gat tct ttc tgg gtg aag aat gaa tta ttg1968Ile Ser Tyr Ser Gly His Asp Ser Phe Trp Val Lys Asn Glu Leu Leu620 625 630cca aac cta gag aaa gaa ggt atg cag att tgc ctt cat gag aga aac2016Pro Asn Leu Glu Lys Glu Gly Met Gln Ile Cys Leu His Glu Arg Asn635 640 645 650ttt gtt cct ggc aag agc att gtg gaa aat atc atc acc tgc att gag2064Phe Val Pro Gly Lys Ser Ile Val Glu Asn Ile Ile Thr Cys Ile Glu655 660 665aag agt tac aag tcc arc ttt gtt ttg tct ccc aac ttt gtc cag agt2112Lys Ser Tyr Lys Ser Ile Phe Val Leu Ser Pro Asn Phe Val Gln Ser670 675 680gaa tgg tgc cat tat gaa ctc tac ttt gcc cat cac aat ctc ttt cat2160Glu Trp Cys His Tyr Glu Leu Tyr Phe Ala His His Asn Leu Phe His685 690 695gaa gga tct aat agc tta atc ctg atc ttg ctg gaa ccc att ccg cag2208Glu Gly Ser Asn Ser Leu Ile Leu Ile Leu Leu Glu Pro Ile Pro Gln700 705 710tac tcc att cct agc agt tat cac aag ctc aaa agt ctc atg gcc agg2256Tyr Ser Ile Pro Ser Ser Tyr His Lys Leu Lys Ser Leu Met Ala Arg715 720 725 730agg act tat ttg gaa tgg ccc aag gaa aag agc aaa cgt ggc ctt ttt2304Arg Thr Tyr Leu Glu Trp Pro Lys Glu Lys Ser Lys Arg Gly Leu Phe735 740 745tgg gct aac tta agg gca gcc att aat att aag ctg aca gag caa gca2352Trp Ala Asn Leu Arg Ala Ala Ile Asn Ile Lys Leu Thr Glu Gln Ala750 755 760aag aaa tagtctaga 2367Lys Lys
<210>2<211>786<212>PRT<213>未知<400>2Met Thr Ser Ile Phe His Phe Ala Ile Ile Phe Met Leu Ile Leu Gln-20 -15 -10Ile Arg Ile Gln Leu Ser Glu Glu Ser Glu Phe Leu Val Asp Arg Ser-5 -1 1 5 10Lys Asn Gly Leu Ile His Val Pro Lys Asp Leu Ser Gln Lys Thr Thr15 20 25Ile Leu Asn Ile Ser Gln Asn Tyr Ile Ser Glu Leu Trp Thr Ser Asp30 35 40Ile Leu Ser Leu Ser Lys Leu Arg Ile Leu Ile Ile Ser His Asn Arg45 50 55Ile Gln Tyr Leu Asp Ile Ser Val Phe Lys Phe Asn Gln Glu Leu Glu60 65 70Tyr Leu Asp Leu Ser His Asn Lys Leu Val Lys Ile Ser Cys His Pro75 80 85 90Thr Val Asn Leu Lys His Leu Asp Leu Ser Phe Asn Ala Phe Asp Ala95 100 105Leu Pro Ile Cys Lys Glu Phe Gly Asn Met Ser Gln Leu Lys Phe Leu110 115 120Gly Leu Ser Thr Thr His Leu Glu Lys Ser Ser Val Leu Pro Ile Ala125 130 135His Leu Asn Ile Ser Lys Val Leu Leu Val Leu Gly Glu Thr Tyr Gly140 145 150Glu Lys Glu Asp Pro Glu Gly Leu Gln Asp Phe Asn Thr Glu Ser Leu155 160 165 170His Ile Val Phe Pro Thr Asn Lys Glu Phe His Phe Ile Leu Asp Val175 180 185Ser Val Lys Thr Val Ala Asn Leu Glu Leu Ser Asn Ile Lys Cys Val190 195 200Leu Glu Asp Asn Lys Cys Ser Tyr Phe Leu Ser Ile Leu Ala Lys Leu205 210 215Gln Thr Asn Pro Lys Leu Ser Ser Leu Thr Leu Asn Asn Ile Glu Thr220 225 230Thr Trp Asn Ser Phe Ile Arg Ile Leu Gln Leu Val Trp His Thr Thr
235 240 245 250Val Trp Tyr Phe Ser Ile Ser Asn Val Lys Leu Gln Gly Gln Leu Asp255 260 265Phe Arg Asp Phe Asp Tyr Ser Gly Thr Ser Leu Lys Ala Leu Ser Ile270 275 280His Gln Val Val Ser Asp Val Phe Gly Phe Pro Gln Ser Tyr Ile Tyr285 290 295Glu Ile Phe Ser Asn Met Asn Ile Lys Asn Phe Thr Val Ser Gly Thr300 305 310Arg Met Val His Met Leu Cys Pro Ser Lys Ile Ser Pro Phe Leu His315 320 325 330Leu Asp Phe Ser Asn Asn Leu Leu Thr Asp Thr Val Phe Glu Asn Cys335 340 345Gly His Leu Thr Glu Leu Glu Thr Leu Ile Leu Gln Met Asn Gln Leu350 355 360Lys Glu Leu Ser Lys Ile Ala Glu Met Thr Thr Gln Met Lys Ser Leu365 370 375Gln Gln Leu Asp Ile Ser Gln Asn Ser Val Ser Tyr Asp Glu Lys Lys380 385 390Gly Asp Cys Ser Trp Thr Lys Ser Leu Leu Ser Leu Asn Met Ser Ser395 400 405 410Asn Ile Leu Thr Asp Thr Ile Phe Arg Cys Leu Pro Pro Arg Ile Lys415 420 425Val Leu Asp Leu His Ser Asn Lys Ile Lys Ser Ile Pro Lys Gln Val430 435 440Val Lys Leu Glu Ala Leu Gln Glu Leu Asn Val Ala Phe Asn Ser Leu445 450 455Thr Asp Leu Pro Gly Cys Gly Ser Phe Ser Ser Leu Ser Val Leu Ile460 465 470Ile Asp His Asn Ser Val Ser His Pro Ser Ala Asp Phe Phe Gln Ser475 480 485 490Cys Gln Lys Met Arg Ser Ile Lys Ala Gly Asp Asn Pro Phe Gln Cys495 500 505Thr Cys Glu Leu Gly Glu Phe Val Lys Asn Ile Asp Gln Val Ser Ser510 515 520Glu Val Leu Glu Gly Trp Pro Asp Ser Tyr Lys Cys Asp Tyr Pro Glu525 530 535Ser Tyr Arg Gly Thr Leu Leu Lys Asp Phe His Met Ser Glu Leu Ser
540 545 550Cys Asn Ile Thr Leu Leu Ile Val Thr Ile Val Ala Thr Met Leu Val555 560 565 570Leu Ala Val Thr Val Thr Ser Leu Cys Ile Tyr Leu Asp Leu Pro Trp575 580 585Tyr Leu Arg Mer Val Cys Gln Trp Thr Gln Thr Arg Arg Arg Ala Arg590 595 600Asn Ile Pro Leu Glu Glu Leu Gln Arg Asn Leu Gln Phe His Ala Phe605 610 615Ile Ser Tyr Ser Gly His Asp Ser Phe Trp Val Lys Asn Glu Leu Leu620 625 630Pro Asn Leu Glu Lys Glu Gly Met Gln Ile Cys Leu His Glu Arg Asn635 640 645 650Phe Val Pro Gly Lys Ser Ile Val Glu Asn Ile Ile Thr Cys Ile Glu655 660 665Lys Ser Tyr Lys Ser Ile Phe Val Leu Ser Pro Asn Phe Val Gln Ser670 675 680Glu Trp Cys His Tyr Glu Leu Tyr Phe Ala His His Asn Leu Phe His685 690 695Glu Gly Ser Asn Ser Leu Ile Leu Ile Leu Leu Glu Pro Ile Pro Gln700 705 710Tyr Ser Ile Pro Ser Ser Tyr His Lys Leu Lys Ser Leu Met Ala Arg715 720 725 730Arg Thr Tyr Leu Glu Trp Pro Lys Glu Lys Ser Lys Arg Gly Leu Phe735 740 745Trp Ala Asn Leu Arg Ala Ala Ile Asn Ile Lys Leu Thr Glu Gln Ala750 755 760Lys Lys<210>3<211>2355<212>DNA<213>未知<220>
<223>未知生物的说明灵长类动物；推测为人(Homo sapiens)<220>
<221>CDS
<222>(L)..(2352)<220>
<22l>mat_肽<222>(67)..(2352)<400>3atg cca cat act ttg tgg atg gtg tgg gtc ttg ggg gtc atc atc agc 48Met Pro His Thr Leu Trp Met Val Trp Val Leu Gly Val Ile Ile Ser-20 -15 -10ctc tcc aag gaa gaa tcc tcc aat cag gct tct ctg tct tgt gac cgc 96Leu Ser Lys Glu Glu Ser Ser Asn Gln Ala Ser Leu Ser Cys Asp Arg-5 -1 1 5 10aat ggt atc tgc aag ggc agc tca gga tct tta aac tcc att ccc tca144Asn Gly Ile Cys Lys Gly Ser Ser Gly Ser Leu Asn Ser Ile Pro Ser15 20 25ggg ctc aca gaa gct gta aaa agc ctt gac ctg tcc aac aac agg atc192Gly Leu Thr Glu Ala Val Lys Ser Leu Asp Leu Ser Asn Asn Arg Ile30 35 40acc tac att agc aac agt gac cta cag agg tgt gtg aac ctc cag gct240Thr Tyr Ile Ser Asn Ser Asp Leu Gln Arg Cys Val Asn Leu Gln Ala45 50 55ctg gtg ctg aca tcc aat gga att aac aca ata gag gaa gat tct ttt288Leu Val Leu Thr Ser Asn Gly Ile Asn Thr Ile Glu Glu Asp Ser Phe60 65 70tct tcc ctg ggc agt ctt gaa cat tta gac tta tcc tat aat tac tta336Ser Ser Leu Gly Ser Leu Glu His Leu Asp Leu Ser Tyr Asn Tyr Leu75 80 85 90tct aat tta tcg tct tcc tgg ttc aag ccc ctt tct tct tta aca ttc384Ser Asn Leu Ser Ser Ser Trp Phe Lys Pro Leu Ser Ser Leu Thr Phe95 100 105tta aac tta ctg gga aat cct tac aaa acc cta ggg gaa aca tct ctt432Leu Asn Leu Leu Gly Asn Pro Tyr Lys Thr Leu Gly Glu Thr Ser Leu110 115 120ttt tct cat ctc aca aaa ttg caa atc ctg aga gtg gga aat atg gac480Phe Ser His Leu Thr Lys Leu Gln Ile Leu Arg Val Gly Asn Met Asp125 130 135acc ttc act aag att caa aga aaa gat ttt gct gga ctt acc ttc ctt528Thr Phe Thr Lys Ile Gln Arg Lys Asp Phe Ala Gly Leu Thr Phe Leu140 145 150gag gaa ctt gag att gat gct tca gat cta cag agc tat gag cca aaa576Glu Glu Leu Glu Ile Asp Ala Ser Asp Leu Gln Ser Tyr Glu Pro Lys155 160 165 170agt ttg aag tca att cag aac gta agt cat ctg atc ctt cat atg aag624Ser Leu Lys Ser Ile Gln Asn Val Ser His Leu Ile Leu His Met Lys
175 180 185cag cat att tta ctg ctg gag att ttt gta gat gtt aca agt tcc gtg672Gln His Ile Leu Leu Leu Glu Ile Phe Val Asp Val Thr Ser Ser Val190 195 200gaa tgt ttg gaa ctg cga gat act gat ttg gac act ttc cat ttt tca720Glu Cys Leu Glu Leu Arg Asp Thr Asp Leu Asp Thr Phe His Phe Ser205 210 215gaa cta tcc act ggt gaa aca aat tca ttg att aaa aag ttt aca ttt768Glu Leu Ser Thr Gly Glu Thr Asn Ser Leu Ile Lys Lys Phe Thr Phe220 225 230aga aat gtg aaa atc acc gat gaa agt ttg ttt cag gtt atg aaa ctt816Arg Asn Val Lys Ile Thr Asp Glu Ser Leu Phe Gln Val Met Lys Leu235 240 245 250ttg aat cag att tct gga ttg tta gaa tta gag ttt gat gac tgt acc864Leu Asn Gln Ile Ser Gly Leu Leu Glu Leu Glu Phe Asp Asp Cys Thr255 260 265ctt aat gga gtt ggt aat ttt aga gca tct gat aat gac aga gtt ata912Leu Asn Gly Val Gly Asn Phe Arg Ala Ser Asp Asn Asp Arg Val Ile270 275 280gat cca ggt aaa gtg gaa acg tta aca atc cgg agg ctg cat att cca960Asp Pro Gly Lys Val Glu Thr Leu Thr Ile Arg Arg Leu His Ile Pro285 290 295agg ttt tac tta ttt tat gat ctg agc act tta tat tca ctt aca gaa 1008Arg Phe Tyr Leu Phe Tyr Asp Leu Ser Thr Leu Tyr Ser Leu Thr Glu300 305 310aga gtt aaa aga atc aca gta gaa aac agt aaa gtt ttt ctg gtt cct 1056Arg Val Lys Arg Ile Thr Val Glu Asn Ser Lys Val Phe Leu Val Pro315 320 325 330tgt tta ctt tca caa cat tta aaa tca tta gaa tac ttg gat ctc agt 1104Cys Leu Leu Ser Gln His Leu Lys Ser Leu Glu Tyr Leu Asp Leu Ser335 340 345gaa aat ttg atg gtt gaa gaa tac ttg aaa aat tca gcc tgt gag gat 1152Glu Asn Leu Met Val Glu Glu Tyr Leu Lys Asn Ser Ala Cys Glu Asp350 355 360gcc tgg ccc tct cta caa act tta att tta agg caa aat cat ttg gca 1200Ala Trp Pro Ser Leu Gln Thr Leu Ile Leu Arg Gln Asn His Leu Ala365 370 375tca ttg gaa aaa acc gga gag act ttg ctc act ctg aaa aac ttg act 1248ser Leu Glu Lys Thr Gly Glu Thr Leu Leu Thr Leu Lys Asn Leu Thr380 385 390aac att gat atc agt aag aat agt ttt cat tct atg cct gaa act tgt 1296Asn Ile Asp Ile Ser Lys Asn Ser Phe His Ser Met Pro Glu Thr Cys395 400 405 410
cag tgg cca gaa aag atg aaa tat ttg aac tta tcc agc aca cga ata1344Gln Trp Pro Glu Lys Met Lys Tyr Leu Asn Leu Ser Ser Thr Arg Ile415 420 425cac agt gta aca ggc tgc att ccc aag aca ctg gaa att tta gat gtt1392His Ser Val Thr Gly Cys Ile Pro Lys Thr Leu Glu Ile Leu Asp Val430 435 440agc aac aac aat ctc aat tta ttt tct ttg aat ttg ccg caa ctc aaa1440Ser Asn Asn Asn Leu Asn Leu Phe Ser Leu Asn Leu Pro Gln Leu Lys445 450 455gaa ctt tat att tcc aga aat aag ttg atg act cta cca gat gcc tcc1488Glu Leu Tyr Ile Ser Arg Asn Lys Leu Met Thr Leu Pro Asp Ala Ser460 465 470ctc tta ccc atg tta cta gta ttg aaa atc agt agg aat gca ata act1536Leu Leu Pro Met Leu Leu Val Leu Lys Ile Ser Arg Asn Ala Ile Thr475 480 485 490acg ttt tct aag gag caa ctt gac tca ttt cac aca ctg aag act ttg1584Thr Phe Ser Lys Glu Gln Leu Asp Ser Phe His Thr Leu Lys Thr Leu495 500 505gaa gct ggt ggc aat aac ttc att tgc tcc tgt gaa ttc ctc tcc ttc1632Glu Ala Gly Gly Asn Asn Phe Ile Cys Ser Cys Glu Phe Leu Ser Phe510 515 520act cag gag cag caa gca ctg gcc aaa gtc ttg att gat tgg cca gca1680Thr Gln Glu Gln Gln Ala Leu Ala Lys Val Leu Ile Asp Trp Pro Ala525 530 535aat tac ctg tgt gac tct cca tcc cat gtg cgt ggc cag cag gtt cag1728Asn Tyr Leu Cys Asp Ser Pro Ser His Val Arg Gly Gln Gln Val Gln540 545 550gat gtc cgc ctc tcg gtg tcg gaa tgt cac agg aca gca ctg gtg tct1776Asp Val Arg Leu Ser Val Ser Glu Cys His Arg Thr Ala Leu Val Ser555 560 565 570ggc atg tgc tgt gct ctg ttc ctg ctg atc ctg ctc acg ggg gtc ctg1824Gly Met Cys Cys Ala Leu Phe Leu Leu Ile Leu Leu Thr Gly Val Leu575 580 585tgc cac cgt ttc cat ggc ctg tgg tat atg aaa atg atg tgg gcc tgg1872Cys His Arg Phe His Gly Leu Trp Tyr Met Lys Met Met Trp Ala Trp590 595 600ctc cag gcc aaa agg aag ccc agg aaa gct ccc agc agg aac atc tgc1920Leu Gln Ala Lys Arg Lys Pro Arg Lys Ala Pro Ser Arg Asn Ile Cys605 610 615tat gat gca ttt gtt tct tac agt gag cgg gat gcc tac tgg gtg gag1968Tyr Asp Ala Phe Val Ser Tyr Ser Glu Arg Asp Ala Tyr Trp Val Glu620 625 630
aac ctt atg gtc cag gag ctg gag aac ttc aat ccc ccc ttc aag ttg2016Asn Leu Met Val Gln Glu Leu Glu Asn Phe Asn Pro Pro Phe Lys Leu635 640 645 650tgt ctt cat aag cgg gac ttc att cct ggc aag tgg atc att gac aat2064Cys Leu His Lys Arg Asp Phe Ile Pro Gly Lys Trp Ile Ile Asp Asn655 660 665atc att gac tcc att gaa aag agc cac aaa act gtc ttt gtg ctt tct2112Ile Ile Asp Ser Ile Glu Lys Ser His Lys Thr Val Phe Val Leu Ser670 675 680gaa aac ttt gtg aag agt gag tgg tgc aag tat gaa ctg gac ttc tcc2160Glu Asn Phe Val Lys Ser Glu Trp Cys Lys Tyr Glu Leu Asp Phe Ser685 690 695cat ttc cgt ctt ttt gaa gag aac aat gat gct gcc att ctc att ctt2208His Phe Arg Leu Phe Glu Glu Asn Asn Asp Ala Ala Ile Leu Ile Leu700 705 710ctg gag ccc att gag aaa aaa gcc att ccc cag cgc ttc tgc aag ctg2256Leu Glu Pro Ile Glu Lys Lys Ala Ile Pro Gln Arg Phe Cys Lys Leu715 720 725 730cgg aag ata atg aac acc aag acc tac ctg gag tgg ccc atg gac gag2304Arg Lys Ile Met Asn Thr Lys Thr Tyr Leu Glu Trp Pro Met Asp Glu735 740 745gct cag cgg gaa gga ttt tgg gta aat ctg aga gct gcg ata aag tcc2352Ala Gln Arg Glu Gly Phe Trp Val Asn Leu Arg Ala Ala Ile Lys Ser750 755 760tag2355<210>4<211>784<212>PRT<213>未知<400>4Met Pro His Thr Leu Trp Met Val Trp Val Leu Gly Val Ile Ile Ser-20 -15 -10Leu Ser Lys Glu Glu Ser Ser Asn Gln Ala Ser Leu Ser Cys Asp Arg-5 -11 5 10Asn Gly Ile Cys Lys Gly Ser Ser Gly Ser Leu Asn Ser Ile Pro Ser15 20 25Gly Leu Thr Glu Ala Val Lys Ser Leu Asp Leu Ser Asn Asn Arg Ile30 35 40Thr Tyr Ile Ser Asn Ser Asp Leu Gln Arg Cys Val Asn Leu Gln Ala45 50 55Leu Val Leu Thr Ser Asn Gly Ile Asn Thr Ile Glu Glu Asp Ser Phe
60 65 70Ser Ser Leu Gly Ser Leu Glu His Leu Asp Leu Ser Tyr Asn Tyr Leu75 80 85 90Ser Asn Leu Ser Ser Ser Trp Phe Lys Pro Leu Ser Ser Leu Thr Phe95 100 105Leu Asn Leu Leu Gly Asn Pro Tyr Lys Thr Leu Gly Glu Thr Ser Leu110 115 120Phe Ser His Leu Thr Lys Leu Gln Ile Leu Arg Val Gly Asn Met Asp125 130 135Thr Phe Thr Lys Ile Gln Arg Lys Asp Phe Ala Gly Leu Thr Phe Leu140 145 150Glu Glu Leu Glu Ile Asp Ala Ser Asp Leu Gln Ser Tyr Glu Pro Lys155 160 165 170Ser Leu Lys Ser Ile Gln Asn Val Ser His Leu Ile Leu His Met Lys175 180 185Gln His Ile Leu Leu Leu Glu Ile Phe Val Asp Val Thr Ser Ser Val190 195 200Glu Cys Leu Glu Leu Arg Asp Thr Asp Leu Asp Thr Phe His Phe Ser205 210 215Glu Leu Ser Thr Gly Glu Thr Asn Ser Leu Ile Lys Lys Phe Thr Phe220 225 230Arg Asn Val Lys Ile Thr Asp Glu Ser Leu Phe Gln Val Met Lys Leu235 240 245 250Leu Asn Gln Ile Ser Gly Leu Leu Glu Leu Glu Phe Asp Asp Cys Thr255 260 265Leu Asn Gly Val Gly Asn Phe Arg Ala Ser Asp Asn Asp Arg Val Ile270 275 280Asp Pro Gly Lys Val Glu Thr Leu Thr Ile Arg Arg Leu His Ile Pro285 290 295Arg Phe Tyr Leu Phe Tyr Asp Leu Ser Thr Leu Tyr Ser Leu Thr Glu300 305 310Arg Val Lys Arg Ile Thr Val Glu Asn Ser Lys Val Phe Leu Val Pro315 320 325 330Cys Leu Leu Ser Gln His Leu Lys Ser Leu Glu Tyr Leu Asp Leu Ser335 340 345Glu Asn Leu Met Val Glu Glu Tyr Leu Lys Asn Ser Ala Cys Glu Asp350 355 360Ala Trp Pro Ser Leu Gln Thr Leu Ile Leu Arg Gln Asn His Leu Ala
365 370 375Ser Leu Glu Lys Thr Gly Glu Thr Leu Leu Thr Leu Lys Asn Leu Thr380 385 390Asn Ile Asp Ile Ser Lys Asn Ser Phe His Ser Met Pro Glu Thr Cys395 400 405 410Gln Trp Pro Glu Lys Met Lys Tyr Leu Asn Leu Ser Ser Thr Arg Ile415 420 425His Ser Val Thr Gly Cys Ile Pro Lys Thr Leu Glu Ile Leu Asp Val430 435 440Ser Asn Asn Asn Leu Asn Leu Phe Ser Leu Asn Leu Pro Gln Leu Lys445 450 455Glu Leu Tyr Ile Ser Arg Asn Lys Leu Met Thr Leu Pro Asp Ala Ser460 465 470Leu Leu Pro Met Leu Leu Val Leu Lys Ile Ser Arg Asn Ala Ile Thr475 480 485 490Thr Phe Ser Lys Glu Gln Leu Asp Ser Phe His Thr Leu Lys Thr Leu495 500 505Glu Ala Gly Gly Asn Asn Phe Ile Cys Ser Cys Glu Phe Leu Ser Phe510 515 520Thr Gln Glu Gln Gln Ala Leu Ala Lys Val Leu Ile Asp Trp Pro Ala525 530 535Asn Tyr Leu Cys Asp Ser Pro Ser His Val Arg Gly Gln Gln Val Gln540 545 550Asp Val Arg Leu Ser Val Ser Glu Cys His Arg Thr Ala Leu Val Ser555 560 565 570Gly Met Cys Cys Ala Leu Phe Leu Leu Ile Leu Leu Thr Gly Val Leu575 580 585Cys His Arg Phe His Gly Leu Trp Tyr Met Lys Met Met Trp Ala Trp590 595 600Leu Gln Ala Lys Arg Lys Pro Arg Lys Ala Pro Ser Arg Asn Ile Cys605 610 615Tyr Asp Ala Phe Val Ser Tyr Ser Glu Arg Asp Ala Tyr Trp Val Glu620 625 630Asn Leu Met Val Gln Glu Leu Glu Asn Phe Asn Pro Pro Phe Lys Leu635 640 645 650Cys Leu His Lys Arg Asp Phe Ile Pro Gly Lys Trp Ile Ile Asp Asn655 660 665Ile Ile Asp Ser Ile Glu Lys Ser His Lys Thr Val Phe Val Leu Ser
670 675 680Glu Asn Phe Val Lys Ser Glu Trp Cys Lys Tyr Glu Leu Asp Phe Ser685 690 695His Phe Arg Leu Phe Glu Glu Asn Asn Asp Ala Ala Ile Leu Ile Leu700 705 710Leu Glu Pro Ile Glu Lys Lys Ala Ile Pro Gln Arg Phe Cys Lys Leu715 720 725 730Arg Lys Ile Met Asn Thr Lys Thr Tyr Leu Glu Trp Pro Met Asp Glu735 740 745Ala Gln Arg Glu Gly Phe Trp Val Asn Leu Arg Ala Ala Ile Lys Ser750 755 760<210>5<211>2715<212>DNA<213>未知<220>
<223>未知生物的说明灵长类动物；推测为人(Homo sapiens)<220>
<221>CDS<222>(1)..(2712)<220>
<221>mat_肽<222>(64)..(2712)<400>5atg aga cag act ttg cct tgt atc tac ttt tgg ggg ggc ctt ttg ccc 48Met Arg Gln Thr Leu Pro Cys Ile Tyr Phe Trp Gly Gly Leu Leu Pro-20 -15 -10ttt ggg atg ctg tgt gca tcc tcc acc acc aag tgc act gtt agc cat 96Phe Gly Met Leu Cys Ala Ser Ser Thr Thr Lys Cys Thr Val Ser His-5 -1 1 5 10gaa gtt gct gac tgc agc cac ctg aag ttg act cag gta ccc gat gat144Glu Val Ala Asp Cys Ser His Leu Lys Leu Thr Gln Val Pro Asp Asp15 20 25cta ccc aca aac ata aca gtg ttg aac ctt acc cat aat caa ctc aga192Leu Pro Thr Asn Ile Thr Val Leu Asn Leu Thr His Asn Gln Leu Arg30 35 40aga tta cca gcc gcc aac ttc aca agg tat agc cag cta act agc ttg240Arg Leu Pro Ala Ala Asn Phe Thr Arg Tyr Ser Gln Leu Thr Ser Leu45 50 55
gat gta gga ttt aac acc atc tca aaa ctg gag cca gaa ttg tgc cag288Asp Val Gly Phe Asn Thr Ile Ser Lys Leu Glu Pro Glu Leu Cys Gln60 65 70 75aaa ctt ccc atg tta aaa gtt ttg aac ctc cag cac aat gag cta tct336Lys Leu Pro Met Leu Lys Val Leu Asn Leu Gln His Asn Glu Leu Ser80 85 90caa ctt tct gat aaa acc ttt gcc ttc tgc acg aat ttg act gaa ctc384Gln Leu Ser Asp Lys Thr Phe Ala Phe Cys Thr Asn Leu Thr Glu Leu95 100 105cat ctc atg tcc aac tca atc cag aaa att aaa aat aat ccc ttt gtc432His Leu Met Ser Asn Ser Ile Gln Lys Ile Lys Asn Asn Pro Phe Val110 115 120aag cag aag aat tta atc aca tta gat ctg tct cat aat ggc ttg tca480Lys Gln Lys Asn Leu Ile Thr Leu Asp Leu Ser His Asn Gly Leu Ser125 130 135tct aca aaa tta gga act cag gtt cag ctg gaa aat ctc caa gag ctt528Ser Thr Lys Leu Gly Thr Gln Val Gln Leu Glu Asn Leu Gln Glu Leu140 145 150 155cta tta tca aac aat aaa att caa gcg cta aaa agt gaa gaa ctg gat576Leu Leu Ser Asn Asn Lys Ile Gln Ala Leu Lys Ser Glu Glu Leu Asp160 165 170atc ttt gcc aat tca tct tta aaa aaa tta gag ttg tca tcg aat caa624Ile Phe Ala Asn Ser Ser Leu Lys Lys Leu Glu Leu Ser Ser Asn Gln175 180 185att aaa gag ttt tct cca ggg tgt ttt cac gca att gga aga tta ttt672Ile Lys Glu Phe Ser Pro Gly Cys Phe His Ala Ile Gly Arg Leu Phe190 195 200ggc ctc ttt ctg aac aat gtc cag ctg ggt ccc agc ctt aca gag aag720Gly Leu Phe Leu Asn Asn Val Gln Leu Gly Pro Ser Leu Thr Glu Lys205 210 215cta tgt ttg gaa tta gca aac aca agc att cgg aat ctg tct ctg agt768Leu Cys Leu Glu Leu Ala Asn Thr Ser Ile Arg Asn Leu Ser Leu Ser220 225 230 235aac agc cag ctg tcc acc acc agc aat aca act ttc ttg gga cta aag816Asn Ser Gln Leu Ser Thr Thr Ser Asn Thr Thr Phe Leu Gly Leu Lys240 245 250tgg aca aat ctc act atg ctc gat ctt tcc tac aac aac tta aat gtg864Trp Thr Asn Leu Thr Met Leu Asp Leu Ser Tyr Asn Asn Leu Asn Val255 260 265gtt ggt aac gat tcc ttt get tgg ctt cca caa cta gaa tat ttc ttc912Val Gly Asn Asp Ser Phe Ala Trp Leu Pro Gln Leu Glu Tyr Phe Phe270 275 280cta gag tat aat aat ata cag cat ttg ttt tct cac tct ttg cac ggg960
Leu Glu Tyr Asn Asn Ile Gln His Leu Phe Ser His Ser Leu His Gly285 290 295ctt ttc aat gtg agg tac ctg aat ttg aaa cgg tct ttt act aaa caa1008Leu Phe Asn Val Arg Tyr Leu Asn Leu Lys Arg Ser Phe Thr Lys Gln300 305 310 315agt att tcc ctt gcc tca ctc ccc aag att gat gat ttt tct ttt cag1056Ser Ile Ser Leu Ala Ser Leu Pro Lys Ile Asp Asp Phe Ser Phe Gln320 325 330tgg cta aaa tgt ttg gag cac ctt aac atg gaa gat aat gat att cca1104Trp Leu Lys Cys Leu Glu His Leu Asn Met Glu Asp Asn Asp Ile Pro335 340 345ggc ata aaa agc aat atg ttc aca gga ttg ata aac ctg aaa tac tta1152Gly Ile Lys Ser Asn Met Phe Thr Gly Leu Ile Asn Leu Lys Tyr Leu350 355 360agt cta tcc aac tcc ttt aca agt ttg cga act ttg aca aat gaa aca1200Ser Leu Ser Asn Ser Phe Thr Ser Leu Arg Thr Leu Thr Asn Glu Thr365 370 375ttt gta tca ctt gct cat tct ccc tta cac ata ctc aac cta acc aag1248Phe Val Ser Leu Ala His Ser Pro Leu His Ile Leu Asn Leu Thr Lys380 385 390 395aat aaa atc tca aaa ata gag agt gat gct ttc tct tgg ttg ggc cac1296Asn Lys Ile Ser Lys Ile Glu Ser Asp Ala Phe Ser Trp Leu Gly His400 405 410cta gaa gta ctt gac ctg ggc ctt aat gaa att ggg caa gaa ctc aca1344Leu Glu Val Leu Asp Leu Gly Leu Asn Glu Ile Gly Gln Glu Leu Thr415 420 425ggc cag gaa tgg aga ggt cta gaa aat att ttc gaa atc tat ctt tcc1392Gly Gln Glu Trp Arg Gly Leu Glu Asn Ile Phe Glu Ile Tyr Leu Ser430 435 440tac aac aag tac ctg cag ctg act agg aac tcc ttt gcc ttg gtc cca1440Tyr Asn Lys Tyr Leu Gln Leu Thr Arg Asn Ser Phe Ala Leu Val Pro445 450 455agc ctt caa cga ctg atg ctc cga agg gtg gcc ctt aaa aat gtg gat1488Ser Leu Gln Arg Leu Met Leu Arg Arg Val Ala Leu Lys Asn Val Asp460 465 470 475agc tct cct tca cca ttc cag cct ctt cgt aac ttg acc att ctg gat1536Ser Ser Pro Ser Pro Phe Gln Pro Leu Arg Asn Leu Thr Ile Leu Asp480 485 490cta agc aac aac aac ata gcc aac ata aat gat gac atg ttg gag ggt1584Leu Ser Asn Asn Asn Ile Ala Asn Ile Asn Asp Asp Met Leu Glu Gly495 500 505ctt gag aaa cta gaa att ctc gat ttg cag cat aac aac tta gca cgg1632Leu Glu Lys Leu Glu Ile Leu Asp Leu Gln His Asn Asn Leu Ala Arg
510 515 520ctc tgg aaa cac gca aac cct ggt ggt ccc att tat ttc cta aag ggt1680Leu Trp Lys His Ala Asn Pro Gly Gly Pro Ile Tyr Phe Leu Lys Gly525 530 535ctg tct cac ctc cac atc ctt aac ttg gag tcc aac ggc ttt gac gag1728Leu Ser His Leu His Ile Leu Asn Leu Glu Ser Asn Gly Phe Asp Glu540 545 550 555atc cca gtt gag gtc ttc aag gat tta ttt gaa cta aag atc atc gat1776Ile Pro Val Glu Val Phe Lys Asp Leu Phe Glu Leu Lys Ile Ile Asp560 565 570tta gga ttg aat aat tta aac aca ctt cca gca tct gtc ttt aat aat1824Leu Gly Leu Asn Asn Leu Asn Thr Leu Pro Ala Ser Val Phe Asn Asn575 580 585cag gtg tct cta aag tca ttg aac ctt cag aag aat ctc ata aca tcc1872Gln Val Ser Leu Lys Ser Leu Asn Leu Gln Lys Asn Leu Ile Thr Ser590 595600gtt gag aag aag gtt ttc ggg cca gct ttc agg aac ctg act gag tta1920Val Glu Lys Lys Val Phe Gly Pro Ala Phe Arg Asn Leu Thr Glu Leu605 610 615gat atg cgc ttt aat ccc ttt gat tgc acg tgt gaa agt att gcc tgg1968Asp Met Arg Phe Asn Pro Phe Asp Cys Thr Cys Glu Ser Ile Ala Trp620 625 630 635ttt gtt aat tgg att aac gag acc cat acc aac atc cct gag ctg tca2016Phe Val Asn Trp Ile Asn Glu Thr His Thr Asn Ile Pro Glu Leu Ser640 645 650agc cac tac ctt tgc aac act cca cct cac tat cat ggg ttc cca gtg2064Ser His Tyr Leu Cys Asn Thr Pro Pro His Tyr His Gly Phe Pro Val655 660 665aga ctt ttt gat aca tca tct tgc aaa gac agt gcc ccc ttt gaa ctc2112Arg Leu Phe Asp Thr Ser Ser Cys Lys Asp Ser Ala Pro Phe Glu Leu670 675 680ttt ttc atg atc aat acc agt atc ctg ttg att ttt atc ttt att gta2160Phe Phe Met Ile Asn Thr Ser Ile Leu Leu Ile Phe Ile Phe Ile Val685 690 695ctt ctc atc cac ttt gag ggc tgg agg ata tct ttt tat tgg aat gtt2208Leu Leu Ile His Phe Glu Gly Trp Arg Ile Ser Phe Tyr Trp Asn Val700 705 710 715tca gta cat cga gtt ctt ggt ttc aaa gaa ata gac aga cag aca gaa2256Ser Val His Arg Val Leu Gly Phe Lys Glu Ile Asp Arg Gln Thr Glu720 725 730cag ttt gaa tat gca gca tat ata att cat gcc tat aaa gat aag gat2304Gln Phe Glu Tyr Ala Ala Tyr Ile Ile His Ala Tyr Lys Asp Lys Asp735 740 745
tgg gtc tgg gaa cat ttc tct tca atg gaa aag gaa gac caa tct ctc2352Trp Val Trp Glu His Phe Ser Ser Met Glu Lys Glu Asp Gln Ser Leu750 755 760aaa ttt tgt ctg gaa gaa agg gac ttt gag gcg ggt gtt ttt gaa cta2400Lys Phe Cys Leu Glu Glu Arg Asp Phe Glu Ala Gly Val Phe Glu Leu765 770 775gaa gca att gtt aac agc atc aaa aga agc aga aaa att att ttt gtt2448Glu Ala Ile Val Asn Ser Ile Lys Arg Ser Arg Lys Ile Ile Phe Val780 785 790 795ata aca cac cat cta tta aaa gac cca tta tgc aaa aga ttc aag gta2496Ile Thr His His Leu Leu Lys Asp Pro Leu Cys Lys Arg Phe Lys Val800 805 810cat cat gca gtt caa caa gct att gaa caa aat ctg gat tcc att ata2544His His Ala Val Gln Gln Ala Ile Glu Gln Asn Leu Asp Ser Ile Ile815 820 825ttg gtt ttc ctt gag gag att cca gat tat aaa ctg aac cat gca ctc2592Leu Val Phe Leu Glu Glu Ile Pro Asp Tyr Lys Leu Asn His Ala Leu830 835 840tgt ttg cga aga gga atg ttt aaa tct cac tgc atc ttg aac tgg cca2640Cys Leu Arg Arg Gly Met Phe Lys Ser His Cys Ile Leu Asn Trp Pro845 850 855gtt cag aaa gaa cgg ata ggt gcc ttt cgt cat aaa ttg caa gta gca2688Val Gln Lys Glu Arg Ile Gly Ala Phe Arg His Lys Leu Gln Val Ala860 865 870 875ctt gga tcc aaa aac tct gta cat taa2715Leu Gly Ser Lys Asn Ser Val His880<210>6<211>904<212>PRT<213>未知<400>6Met Arg Gln Thr Leu Pro Cys Ile Tyr Phe Trp Gly Gly Leu Leu Pro-20 -15 -10Phe Gly Met Leu Cys Ala Ser Ser Thr Thr Lys Cys Thr Val Ser His-5 -1 1 5 10Glu Val Ala Asp Cys Ser His Leu Lys Leu Thr Gln Val Pro Asp Asp15 20 25Leu Pro Thr Asn Ile Thr Val Leu Asn Leu Thr His Asn Gln Leu Arg30 35 40Arg Leu Pro Ala Ala Asn Phe Thr Arg Tyr Ser Gln Leu Thr Ser Leu
45 50 55Asp Val Gly Phe Asn Thr Ile Ser Lys Leu Glu Pro Glu Leu Cys Gln60 65 70 75Lys Leu Pro Met Leu Lys Val Leu Asn Leu Gln His Asn Glu Leu Ser80 85 90Gln Leu Ser Asp Lys Thr Phe Ala Phe Cys Thr Asn Leu Thr Glu Leu95 100 105His Leu Met Ser Asn Ser Ile Gln Lys Ile Lys Asn Asn Pro Phe Val110 115 120Lys Gln Lys Asn Leu Ile Thr Leu Asp Leu Ser His Asn Gly Leu Ser125 130 135Ser Thr Lys Leu Gly Thr Gln Val Gln Leu Glu Asn Leu Gln Glu Leu140 145 150 155Leu Leu Ser Asn Asn Lys Ile Gln Ala Leu Lys Ser Glu Glu Leu Asp160 165 170Ile Phe Ala Asn Ser Ser Leu Lys Lys Leu Glu Leu Ser Ser Asn Gln175 180 185Ile Lys Glu Phe Ser Pro Gly Cys Phe His Ala Ile Gly Arg Leu Phe190 195 200Gly Leu Phe Leu Asn Asn Val Gln Leu Gly Pro Ser Leu Thr Glu Lys205 210 215Leu Cys Leu Glu Leu Ala Asn Thr Ser Ile Arg Asn Leu Ser Leu Ser220 225 230 235Asn Ser Gln Leu Ser Thr Thr Ser Asn Thr Thr Phe Leu Gly Leu Lys240 245 250Trp Thr Asn Leu Thr Met Leu Asp Leu Ser Tyr Asn Asn Leu Asn Val255 260 265Val Gly Asn Asp Ser Phe Ala Trp Leu Pro Gln Leu Glu Tyr Phe Phe270 275 280Leu Glu Tyr Asn Asn Ile Gln His Leu Phe Ser His Ser Leu His Gly285 290 295Leu Phe Asn Val Arg Tyr Leu Asn Leu Lys Arg Ser Phe Thr Lys Gln300 305 310 315Ser lle Ser Leu Ala Ser Leu Pro Lys Ile Asp Asp Phe Ser Phe Gln320 325 330Trp Leu Lys Cys Leu Glu His Leu Asn Met Glu Asp Asn Asp Ile Pro335 340 345Gly Ile Lys Ser Asn Met Phe Thr Gly Leu Ile Asn Leu Lys Tyr Leu
350 355 360Ser Leu Ser Asn Ser Phe Thr Ser Leu Arg Thr Leu Thr Asn Glu Thr365 370 375Phe Val Ser Leu Ala His Ser Pro Leu His Ile Leu Asn Leu Thr Lys380 385 390 395Asn Lys Ile Ser Lys Ile Glu Ser Asp Ala Phe Ser Trp Leu Gly His400 405 410Leu Glu Val Leu Asp Leu Gly Leu Asn Glu Ile Gly Gln Glu Leu Thr415 420 425Gly Gln Glu Trp Arg Gly Leu Glu Asn Ile Phe Glu Ile Tyr Leu Ser430 435 440Tyr Asn Lys Tyr Leu Gln Leu Thr Arg Asn Ser Phe Ala Leu Val Pro445 450 455Ser Leu Gln Arg Leu Mer Leu Arg Arg Val Ala Leu Lys Asn Val Asp460 465 470 475Ser Ser Pro Ser Pro Phe Gln Pro Leu Arg Asn Leu Thr Ile Leu Asp480 485 490Leu Ser Asn Asn Asn Ile Ala Asn Ile Asn Asp Asp Met Leu Glu Gly495 500 505Leu Glu Lys Leu Glu Ile Leu Asp Leu Gln His Asn Asn Leu Ala Arg510 515 520Leu Trp Lys His Ala Asn Pro Gly Gly Pro Ile Tyr Phe Leu Lys Gly525 530 535Leu Ser His Leu His Ile Leu Asn Leu Glu Ser Asn Gly Phe Asp Glu540 545 550 555Ile Pro Val Glu Val Phe Lys Asp Leu Phe Glu Leu Lys Ile Ile Asp560 565 570Leu Gly Leu Asn Asn Leu Asn Thr Leu Pro Ala Ser Val Phe Asn Asn575 580 585Gln Val Ser Leu Lys Ser Leu Asn Leu Gln Lys Asn Leu Ile Thr Ser590 595 600Val Glu Lys Lys Val Phe Gly Pro Ala Phe Arg Asn Leu Thr Glu Leu605 610 615Asp Met Arg Phe Asn Pro Phe Asp Cys Thr Cys Glu Ser Ile Ala Trp620 625 630 635Phe Val Asn Trp Ile Asn Glu Thr His Thr Asn Ile Pro Glu Leu Ser640 645 650Ser His Tyr Leu Cys Asn Thr Pro Pro His Tyr His Gly Phe Pro Val
655 660 665Arg Leu Phe Asp Thr Ser Ser Cys Lys Asp Ser Ala Pro Phe Glu Leu670 675 680Phe Phe Met Ile Asn Thr Ser Ile Leu Leu Ile Phe Ile Phe Ile Val685 690 695Leu Leu Ile His Phe Glu Gly Trp Arg Ile Ser Phe Tyr Trp Asn Val700 705 710 715Ser Val His Arg Val Leu Gly Phe Lys Glu Ile Asp Arg Gln Thr Glu720 725 730Gln Phe Glu Tyr Ala Ala Tyr Ile Ile His Ala Tyr Lys Asp Lys Asp735 740 745Trp Val Trp Glu His Phe Ser Ser Met Glu Lys Glu Asp Gln Ser Leu750 755 760Lys Phe Cys Leu Glu Glu Arg Asp Phe Glu Ala Gly Val Phe Glu Leu765 770 775Glu Ala Ile Val Asn Ser Ile Lys Arg Ser Arg Lys Ile Ile Phe Val780 785 790 795Ile Thr His His Leu Leu Lys Asp Pro Leu Cys Lys Arg Phe Lys Val800 805 810His His Ala Val Gln Gln Ala Ile Glu Gln Asn Leu Asp Ser Ile Ile815 820 825Leu Val Phe Leu Glu Glu Ile Pro Asp Tyr Lys Leu Asn His Ala Leu830 835 840Cys Leu Arg Arg Gly Met Phe Lys Ser His Cys Ile Leu Asn Trp Pro845 850 855Val Gln Lys Glu Arg Ile Gly Ala Phe Arg His Lys Leu Gln Val Ala860 865 870 875Leu Gly Ser Lys Asn Ser Val His880<210>7<211>2400<212>DNA<213>未知<220>
<223>未知生物的说明灵长类动物；推测为人(Homo sapiens)<220>
<221>CDS
<222>(1)..(2397)<400>7atg gag ctg aat ttc tac aaa atc ccc gac aac ctc ccc ttc tca acc 48Met Glu Leu Asn Phe Tyr Lys Ile Pro Asp Asn Leu Pro Phe Ser Thr1 5 10 15aag aac ctg gac ctg agc ttt aat ccc ctg agg cat tta ggc agc tat 96Lys Asn Leu Asp Leu Ser Phe Asn Pro Leu Arg His Leu Gly Ser Tyr20 25 30agc ttc ttc agt ttc cca gaa ctg cag gtg ctg gat tta tcc agg tgt144Ser Phe Phe Ser Phe Pro Glu Leu Gln Val Leu Asp Leu Ser Arg Cys35 40 45gaa atc cag aca att gaa gat ggg gca tat cag agc cta agc cac ctc192Glu Ile Gln Thr Ile Glu Asp Gly Ala Tyr Gln Ser Leu Ser His Leu50 55 60tct acc tta ata ttg aca gga aac ccc atc cag agt tta gcc ctg gga240Ser Thr Leu Ile Leu Thr Gly Asn Pro Ile Gln Ser Leu Ala Leu Gly65 70 75 80gcc ttt tct gga cta tca agt tta cag aag ctg gtg gct gtg gag aca288Ala Phe Ser Gly Leu Ser Ser Leu Gln Lys Leu Val Ala Val Glu Thr85 90 95aat cta gca tct cta gag aac ttc ccc att gga cat ctc aaa act ttg336Asn Leu Ala Ser Leu Glu Asn Phe Pro Ile Gly His Leu Lys Thr Leu100 105 110aaa gaa ctt aat gtg gct cac aat ctt atc caa tct ttc aaa tta cct384Lys Glu Leu Asn Val Ala His Asn Leu Ile Gln Ser Phe Lys Leu Pro115 120 125gag tat ttt tct aat ctg acc aat cta gag cac ttg gac ctt tcc agc432Glu Tyr Phe Ser Asn Leu Thr Asn Leu Glu His Leu Asp Leu Ser Ser130 135 140aac aag att caa agt att tat tgc aca gac ttg cgg gtt cta cat caa480Asn Lys Ile Gln Ser Ile Tyr Cys Thr Asp Leu Arg Val Leu His Gln145 150 155 160atg ccc cta ctc aat ctc tct tta gac ctg tcc ctg aac cct atg aac528Met Pro Leu Leu Asn Leu Ser Leu Asp Leu Ser Leu Asn Pro Met Asn165 170 175ttt atc caa cca ggt gca ttt aaa gaa att agg ctt cat aag ctg act576Phe Ile Gln Pro Gly Ala Phe Lys Glu Ile Arg Leu His Lys Leu Thr180 185 190tta aga aat aat ttt gat agt tta aat gta atg aaa act tgt att caa624Leu Arg Asn Asn Phe Asp Ser Leu Asn Val Met Lys Thr Cys Ile Gln195 200 205ggt ctg gct ggt tta gaa gtc cat cgt ttg gtt ctg gga gaa ttt aga672Gly Leu Ala Gly Leu Glu Val His Arg Leu Val Leu Gly Glu Phe Arg
210 215 220aat gaa gga aac ttg gaa aag ttt gac aaa tct gct cta gag ggc ctg720Asn Glu Gly Asn Leu Glu Lys Phe Asp Lys Ser Ala Leu Glu Gly Leu225 230 235 240tgc aat ttg acc att gaa gaa ttc cga tta gca tac tta gac tac tac768Cys Asn Leu Thr Ile Glu Glu Phe Arg Leu Ala Tyr Leu Asp Tyr Tyr245 250 255ctc gat gat att att gac tta ttt aat tgt ttg aca aat gtt tct tca816Leu Asp Asp Ile Ile Asp Leu Phe Asn Cys Leu Thr Asn Val Ser Ser260 265 270ttt tcc ctg gtg agt gtg act att gaa agg gta aaa gac ttt tct tat864Phe Ser Leu Val Ser Val Thr Ile Glu Arg Val Lys Asp Phe Ser Tyr275 280 285aat ttc gga tgg caa cat tta gaa tta gtt aac tgt aaa ttt gga cag912Asn Phe Gly Trp Gln His Leu Glu Leu Val Asn Cys Lys Phe Gly Gln290 295 300ttt ccc aca ttg aaa ctc aaa tct ctc aaa agg ctt act ttc act tcc960Phe Pro Thr Leu Lys Leu Lys Ser Leu Lys Arg Leu Thr Phe Thr Ser305 310 315 320aac aaa ggt ggg aat gct ttt tca gaa gtt gat cta cca agc ctt gag 1008Asn Lys Gly Gly Asn Ala Phe Ser Glu Val Asp Leu Pro Ser Leu Glu325 330 335ttt cta gat ctc agt aga aat ggc ttg agt ttc aaa ggt tgc tgt tct 1056Phe Leu Asp Leu Ser Arg Asn Gly Leu Ser Phe Lys Gly Cys Cys Ser340 345 350caa agt gat ttt ggg aca acc agc cta aag tat tta gat ctg agc ttc 1104Gln Ser Asp Phe Gly Thr Thr Ser Leu Lys Tyr Leu Asp Leu Ser Phe355 360 365aat ggt gtt att acc atg agt tca aac ttc ttg ggc tta gaa caa cta 1152Asn Gly Val Ile Thr Met Ser Ser Asn Phe Leu Gly Leu Glu Gln Leu370 375 380gaa cat ctg gat ttc cag cat tcc aat ttg aaa caa atg agt gag ttt 1200Glu His Leu Asp Phe Gln His Ser Asn Leu Lys Gln Met Ser Glu Phe385 390 395 400tca gta ttc cta tca ctc aga aac ctc att tac ctt gac att tct cat 1248Ser Val Phe Leu Ser Leu Arg Asn Leu Ile Tyr Leu Asp Ile Ser His405 410 415act cac acc aga gtt gct ttc aat ggc atc ttc aat ggc ttg tcc agt 1296Thr His Thr Arg Val Ala Phe Asn Gly Ile Phe Asn Gly Leu Ser Ser420 425 430ctc gaa gtc ttg aaa atg gct ggc aat tct ttc cag gaa aac ttc ctt 1344Leu Glu Val Leu Lys Met Ala Gly Asn Ser Phe Gln Glu Asn Phe Leu435 440 445
cca gat atc ttc aca gag ctg aga aac ttg acc ttc ctg gac ctc tct1392Pro Asp Ile Phe Thr Glu Leu Arg Asn Leu Thr Phe Leu Asp Leu Ser450 455 460cag tgt caa ctg gag cag ttg tct cca aca gca ttt aac tca ctc tcc1440Gln Cys Gln Leu Glu Gln Leu Ser Pro Thr Ala Phe Asn Ser Leu Ser465 470 475 480agt ctt cag gta cta aat atg agc cac aac aac ttc ttt tca ttg gat1488Ser Leu Gln Val Leu Asn Met Ser His Asn Asn Phe Phe Ser Leu Asp485 490 495acg ttt cct tat aag tgt ctg aac tcc ctc cag gtt ctt gat tac agt1536Thr Phe Pro Tyr Lys Cys Leu Asn Ser Leu Gln Val Leu Asp Tyr Ser500 505 510ctc aat cac ata atg act tcc aaa aaa cag gaa cta cag cat ttt cca1584Leu Asn His Ile Met Thr Ser Lys Lys Gln Glu Leu Gln His Phe Pro515 520 525agt agt cta gct ttc tta aat ctt act cag aat gac ttt gct tgt act1632Ser Ser Leu Ala Phe Leu Asn Leu Thr Gln Asn Asp Phe Ala Cys Thr530 535 540tgt gaa cac cag agt ttc ctg caa tgg atc aag gac cag agg cag ctc1680Cys Glu His Gln Ser Phe Leu Gln Trp Ile Lys Asp Gln Arg Gln Leu545 550 555 560ttg gtg gaa gtt gaa cga atg gaa tgt gca aca cct tca gat aag cag1728Leu Val Glu Val Glu Arg Met Glu Cys Ala Thr Pro Ser Asp Lys Gln565 570 575ggc atg cct gtg ctg agt ttg aat atc acc tgt cag atg aat aag acc1776Gly Met Pro Val Leu Ser Leu Asn Ile Thr Cys Gln Met Asn Lys Thr580 585 590atc att ggt gtg tcg gtc ctc agt gtg ctt gta gta tct gtt gta gca1824Ile Ile Gly Val Ser Val Leu Ser Val Leu Val Val Ser Val Val Ala595 600 605gtt ctg gtc tat aag ttc tat ttt cac ctg atg ctt ctt gct ggc tgc1872Val Leu Val Tyr Lys Phe Tyr Phe His Leu Met Leu Leu Ala Gly Cys610 615 620ata aag tat ggt aga ggt gaa aac atc tat gat gcc ttt gtt atc tac1920Ile Lys Tyr Gly Arg Gly Glu Asn Ile Tyr Asp Ala Phe Val Ile Tyr625 630 635 640tca agc cag gat gag gac tgg gta agg aat gag cta gta aag aat tta1968Ser Ser Gln Asp Glu Asp Trp Val Arg Asn Glu Leu Val Lys Asn Leu645 650 655gaa gaa ggg gtg cct cca ttt cag ctc tgc ctt cac tac aga gac ttt2016Glu Glu Gly Val Pro Pro Phe Gln Leu Cys Leu His Tyr Arg Asp Phe660 665 670
att ccc ggt gtg gcc att gct gcc aac atc atc cat gaa ggt ttc cat2064Ile Pro Gly Val Ala Ile Ala Ala Asn Ile Ile His Glu Gly Phe His675 680 685aaa agc cga aag gtg att gtt gtg gtg tcc cag cac ttc atc cag agc2112Lys Ser Arg Lys Val Ile Val Val Val Ser Gln His Phe Ile Gln Ser690 695 700cgc tgg tgt atc ttt gaa tat gag att gct cag acc tgg cag ttt ctg2160Arg Trp Cys Ile Phe Glu Tyr Glu Ile Ala Gln Thr Trp Gln Phe Leu705 710 715 720agc agt cgt gct ggt atc atc ttc att gtc ctg cag aag gtg gag aag2208Ser Ser Arg Ala Gly Ile Ile Phe Ile Val Leu Gln Lys Val Glu Lys725 730 735acc ctg ctc agg cag cag gtg gag ctg tac cgc ctt ctc agc agg aac2256Thr Leu Leu Arg Gln Gln Val Glu Leu Tyr Arg Leu Leu Ser Arg Asn740 745 750act tac ctg gag tgg gag gac agt gtc ctg ggg cgg cac atc ttc tgg2304Thr Tyr Leu Glu Trp Glu Asp Ser Val Leu Gly Arg His Ile Phe Trp755 760 765aga cga ctc aga aaa gcc ctg ctg gat ggt aaa tca tgg aat cca gaa2352Arg Arg Leu Arg Lys Ala Leu Leu Asp Gly Lys Ser Trp Asn Pro Glu770 775 780gga aca gtg ggt aca gga tgc aat tgg cag gaa gca aca tct atc tga2400Gly Thr Val Gly Thr Gly Cys Asn Trp Gln Glu Ala Thr Ser Ile785 790 795<210>8<211>799<212>PRT<213>未知<400>8Met Glu Leu Asn Phe Tyr Lys Ile Pro Asp Asn Leu Pro Phe Ser Thr1 5 10 15Lys Asn Leu Asp Leu Ser Phe Asn Pro Leu Arg His Leu Gly Ser Tyr20 25 30Ser Phe Phe Ser Phe Pro Glu Leu Gln Val Leu Asp Leu Ser Arg Cys35 40 45Glu Ile Gln Thr Ile Glu Asp Gly Ala Tyr Gln Ser Leu Ser His Leu50 55 60Ser Thr Leu Ile Leu Thr Gly Asn Pro Ile Gln Ser Leu Ala Leu Gly65 70 75 80Ala Phe Ser Gly Leu Ser Ser Leu Gln Lys Leu Val Ala Val Glu Thr85 90 95
Asn Leu Ala Ser Leu Glu Asn Phe Pro Ile Gly His Leu Lys Thr Leu100 105 110Lys Glu Leu Asn Val Ala His Asn Leu Ile Gln Ser Phe Lys Leu Pro115 120 125Glu Tyr Phe Ser Asn Leu Thr Asn Leu Glu His Leu Asp Leu Ser Ser130 135 140Asn Lys Ile Gln Ser Ile Tyr Cys Thr Asp Leu Arg Val Leu His Gln145 150 155 160Met Pro Leu Leu Asn Leu Ser Leu Asp Leu Ser Leu Asn Pro Met Asn165 170 175Phe Ile Gln Pro Gly Ala Phe Lys Glu Ile Arg Leu His Lys Leu Thr180 185 190Leu Arg Asn Asn Phe Asp Ser Leu Asn Val Met Lys Thr Cys Ile Gln195 200 205Gly Leu Ala Gly Leu Glu Val His Arg Leu Val Leu Gly Glu Phe Arg210 215 220Asn Glu Gly Asn Leu Glu Lys Phe Asp Lys Ser Ala Leu Glu Gly Leu225 230 235 240Cys Asn Leu Thr Ile Glu Glu Phe Arg Leu Ala Tyr Leu Asp Tyr Tyr245 250 255Leu Asp Asp Ile Ile Asp Leu Phe Asn Cys Leu Thr Asn Val Ser Ser260 265 270Phe Ser Leu Val Sar Val Thr Ile Glu Arg Val Lys Asp Phe Ser Tyr275 280 285Asn Phe Gly Trp Gln His Leu Glu Leu Val Asn Cys Lys Phe Gly Gln290 295 300Phe Pro Thr Leu Lys Leu Lys Ser Leu Lys Arg Leu Thr Phe Thr Ser305 310 315 320Asn Lys Gly Gly Asn Ala Phe Ser Glu Val Asp Leu Pro Ser Leu Glu325 330 335Phe Leu Asp Leu Ser Arg Asn Gly Leu Ser Phe Lys Gly Cys Cys Ser340 345 350Gln Ser Asp Phe Gly Thr Thr Ser Leu Lys Tyr Leu Asp Leu Ser Phe355 360 365Asn Gly Val Ile Thr Met Ser Ser Asn Phe Leu Gly Leu Glu Gln Leu370 375 380Glu His Leu Asp Phe Gln His Ser Asn Leu Lys Gln Met Ser Glu Phe385 390 395 400
Ser Val Phe Leu Ser Leu Arg Asn Leu Ile Tyr Leu Asp Ile Ser His405 410 415Thr His Thr Arg Val Ala Phe Asn Gly Ile Phe Asn Gly Leu Ser Ser420 425 430Leu Glu Val Leu Lys Met Ala Gly Asn Ser Phe Gln Glu Asn Phe Leu435 440 445Pro Asp Ile Phe Thr Glu Leu Arg Asn Leu Thr Phe Leu Asp Leu Ser450 455 460Gln Cys Gln Leu Glu Gln Leu Ser Pro Thr Ala Phe Asn Ser Leu Ser465 470 475 480Ser Leu Gln Val Leu Asn Met Ser His Asn Asn Phe Phe Ser Leu Asp485 490 495Thr Phe Pro Tyr Lys Cys Leu Asn Ser Leu Gln Val Leu Asp Tyr Ser500 505 510Leu Asn His Ile Met Thr Ser Lys Lys Gln Glu Leu Gln His Phe Pro515 520 525Ser Ser Leu Ala Phe Leu Asn Leu Thr Gln Asn Asp Phe Ala Cys Thr530 535 540Cys Glu His Gln Ser Phe Leu Gln Trp Ile Lys Asp Gln Arg Gln Leu545 550 555 560Leu Val Glu Val Glu Arg Met Glu Cys Ala Thr Pro Ser Asp Lys Gln565 570 575Gly Met Pro Val Leu Ser Leu Asn Ile Thr Cys Gln Met Asn Lys Thr580 585 590Ile Ile Gly Val Ser Val Leu Ser Val Leu Val Val Ser Val Val Ala595 600 605Val Leu Val Tyr Lys Phe Tyr Phe His Leu Met Leu Leu Ala Gly Cys610 615 620Ile Lys Tyr Gly Arg Gly Glu Asn Ile Tyr Asp Ala Phe Val Ile Tyr625 630 635 640Ser Ser Gln Asp Glu Asp Trp Val Arg Asn Glu Leu Val Lys Asn Leu645 650 655Glu Glu Gly Val Pro Pro Phe Gln Leu Cys Leu His Tyr Arg Asp Phe660 665 670Ile Pro Gly Val Ala Ile Ala Ala Asn Ile Ile His Glu Gly Phe His675 680 685Lys Ser Arg Lys Val Ile Val Val Val Ser Gln His Phe Ile Gln Ser690 695 700
Arg Trp Cys Ile Phe Glu Tyr Glu Ile Ala Gln Thr Trp Gln Phe Leu705 710 715 720ser Ser Arg Ala Gly Ile Ile Phe Ile Val Leu Gln Lys Val Glu Lys725 730 735Thr Leu Leu Arg Gln Gln Val Glu Leu Tyr Arg Leu Leu Ser Arg Asn740 745 750Thr Tyr Leu Glu Trp Glu Asp Ser Val Leu Gly Arg His Ile Phe Trp755 760 765Arg Arg Leu Arg Lys Ala Leu Leu Asp Gly Lys Ser Trp Asn Pro Glu770 775 780Gly Thr Val Gly Thr Gly Cys Asn Trp Gln Glu Ala Thr Ser Ile785 790 795<210>9<211>1275<212>DNA<213>未知<220>
<223>未知生物的说明灵长类动物；推测为人(Homo sapiens)<220>
<221>CDS<222>(1)..(1095)<400>9tgt tgg gat gtt ttt gag gga ctt tct cat ctt caa gtt ctg tat ttg 48Cys Trp Asp Val Phe Glu Gly Leu Ser His Leu Gln Val Leu Tyr Leu1 5 10 15aat cat aac tat ctt aat tcc ctt cca cca gga gta ttt agc cat ctg 96Asn His Asn Tyr Leu Asn Ser Leu Pro Pro Gly Val Phe Ser His Leu20 25 30act gca tta agg gga cta agc ctc aac tcc aac agg ctg aca gtt ctt144Thr Ala Leu Arg Gly Leu Ser Leu Asn Ser Asn Arg Leu Thr Val Leu35 40 45tct cac aat gat tta cct gct aat tta gag atc ctg gac ata tcc agg192Ser His Asn Asp Leu Pro Ala Asn Leu Glu Ile Leu Asp Ile Ser Arg50 55 60aac cag ctc cta gct cct aat cct gat gta ttt gta tca ctt agt gtc240Asn Gln Leu Leu Ala Pro Asn Pro Asp Val Phe Val Ser Leu Ser Val65 70 75 80ttg gat ata act cat aac aag ttc att tgt gaa tgt gaa ctt agc act288Leu Asp Ile Thr His Asn Lys Phe Ile Cys Glu Cys Glu Leu Ser Thr85 90 95
ttt atc aat tgg ctt aat cac acc aat gtc act ata gct ggg cct cct336Phe Ile Asn Trp Leu Asn His Thr Asn Val Thr Ile Ala Gly Pro Pro100 105 110gca gac ata tat tgt gtg tac cct gac tcg ttc tct ggg gtt tcc ctc384Ala Asp Ile Tyr Cys Val Tyr Pro Asp Ser Phe Ser Gly Val Ser Leu115 120 125ttc tct ctt tcc acg gaa ggt tgt gat gaa gag gaa gtc tta aag tcc432Phe Ser Leu Ser Thr Glu Gly Cys Asp Glu Glu Glu Val Leu Lys Ser130 135 140cta aag ttc tcc ctt ttc att gta tgc act gtc act ctg act ctg ttc480Leu Lys Phe Set Leu Phe Ile Val Cys Thr Val Thr Leu Thr Leu Phe145 150 155 160ctc atg acc atc ctc aca gtc aca aag ttc cgg ggc ttc tgt ttt atc528Leu Met Thr Ile Leu Thr Val Thr Lys Phe Arg Gly Phe Cys Phe Ile165 170 175tgt tat aag aca gcc cag aga ctg gtg ttc aag gac cat ccc cag ggc576Cys Tyr Lys Thr Ala Gln Arg Leu Val Phe Lys Asp His Pro Gln Gly180 185 190aca gaa cct gat atg tac aaa tat gat gcc tat ttg tgc ttc agc agc624Thr Glu Pro Asp Met Tyr Lys Tyr Asp Ala Tyr Leu Cys Phe Ser Ser195 200 205aaa gac ttc aca tgg gtg cag aat gct ttg ctc aaa cac ctg gac act672Lys Asp Phe Thr Trp Val Gln Asn Ala Leu Leu Lys His Leu Asp Thr210 215 220caa tac agt gac caa aac aga ttc aac ctg tgc ttt gaa gaa aga gac720Gln Tyr Ser Asp Gln Asn Arg Phe Asn Leu Cys Phe Glu Glu Arg Asp225 230 235 240ttt gtc cca gga gaa aac cgc att gcc aat atc cag gat gcc atc tgg768Phe Val Pro Gly Glu Asn Arg Ile Ala Asn Ile Gln Asp Ala Ile Trp245 250 255aac agt aga aag atc gtt tgt ctt gtg agc aga cac ttc ctt aga gat816Asn Ser Arg Lys Ile Val Cys Leu Val Ser Arg His Phe Leu Arg Asp260 265 270ggc tgg tgc ctt gaa gcc ttc agt tat gcc cag ggc agg tgc tta tct864Gly Trp Cys Leu Glu Ala Phe Ser Tyr Ala Gln Gly Arg Cys Leu Ser275 280 285gac ctt aac agt gct ctc atc atg gtg gtg gtt ggg tcc ttg tcc cag912Asp Leu Asn Ser Ala Leu Ile Met Val Val Val Gly Ser Leu Ser Gln290 295 300tac cag ttg atg aaa cat caa tcc atc aga ggc ttt gta cag aaa cag960Tyr Gln Leu Met Lys His Gln Ser Ile Arg Gly Phe Val Gln Lys Gln305 310 315 320
cag tat ttg agg tgg cct gag gat ctc cag gat gtt ggc tgg ttt ctt1008Gln Tyr Leu Arg Trp Pro Glu Asp Leu Gln Asp Val Gly Trp Phe Leu325 330 335cat aaa ctc tct caa cag ata cta aag aaa gaa aag gaa aag aag aaa1056His Lys Leu Ser Gln Gln Ile Leu Lys Lys Glu Lys Glu Lys Lys Lys340 345 350gac aat aac att ccg ttg caa act gta gca acc atc tcc taatcaaagg 1105Asp Asn Asn Ile Pro Leu Gln Thr Val Ala Thr Ile Ser355 360 365agcaatttcc aacttatctc aagccacaaa taactcttca ctttgtattt gcaccaagtt 1165atcattttgg ggtcctctct ggaggttttt tttttctttt tgctactatg aaaacaacat 1225aaatctctca attttcgtat caaaaaaaaa aaaaaaaaaa tggcggccgc 1275<210>10<211>365<212>PRT<213>未知<400>10Cys Trp Asp Val Phe Glu Gly Leu Ser His Leu Gln Val Leu Tyr Leu1 5 10 15Asn His Asn Tyr Leu Asn Ser Leu Pro Pro Gly Val Phe Ser His Leu20 25 30Thr Ala Leu Arg Gly Leu Ser Leu Asn Ser Asn Arg Leu Thr Val Leu35 40 45Ser His Asn Asp Leu Pro Ala Asn Leu Glu Ile Leu Asp Ile Ser Arg50 55 60Asn Gln Leu Leu Ala Pro Asn Pro Asp Val Phe Val Ser Leu Ser Val65 70 75 80Leu Asp Ile Thr His Asn Lys Phe Ile Cys Glu Cys Glu Leu Ser Thr85 90 95Phe Ile Asn Trp Leu Asn His Thr Asn Val Thr Ile Ala Gly Pro Pro100 105 110Ala Asp Ile Tyr Cys Val Tyr Pro Asp Ser Phe Ser Gly Val Ser Leu115 120 125Phe Ser Leu Ser Thr Glu Gly Cys Asp Glu Glu Glu Val Leu Lys Ser130 135 140Leu Lys Phe Ser Leu Phe Ile Val Cys Thr Val Thr Leu Thr Leu Phe145 150 155 160Leu Met Thr Ile Leu Thr Val Thr Lys Phe Arg Gly Phe Cys Phe Ile165 170 175
Cys Tyr Lys Thr Ala Gln Arg Leu Val Phe Lys Asp His Pro Gln Gly180 185 190Thr Glu Pro Asp Met Tyr Lys Tyr Asp Ala Tyr Leu Cys Phe Ser Ser195 200 205Lys Asp Phe Thr Trp Val Gln Asn Ala Leu Leu Lys His Leu Asp Thr210 215 220Gln Tyr Ser Asp Gln Asn Arg Phe Asn Leu Cys Phe Glu Glu Arg Asp225 230 235 240Phe Val Pro Gly Glu Asn Arg Ile Ala Asn Ile Gln Asp Ala Ile Trp245 250 255Asn Ser Arg Lys Ile Val Cys Leu Val Ser Arg His Phe Leu Arg Asp260 265 270Gly Trp Cys Leu Glu Ala Phe Ser Tyr Ala Gln Gly Arg Cys Leu Ser275 280 285Asp Leu Asn Ser Ala Leu Ile Met Val Val Val Gly Ser Leu Ser Gln290 295 300Tyr Gln Leu Met Lys His Gln Ser Ile Arg Gly Phe Val Gln Lys Gln305 310 315 320Gln Tyr Leu Arg Trp Pro Glu Asp Leu Gln Asp Val Gly Trp Phe Leu325 330 335His Lys Leu Ser Gln Gln Ile Leu Lys Lys Glu Lys Glu Lys Lys Lys340 345 350Asp Asn Asn Ile Pro Leu Gln Thr Val Ala Thr Ile Ser355 360 365<210>11<211>3138<212>DNA<213>未知<220>
<223>未知生物的说明灵长类动物；推测为人(Homo sapiens)<220>
<221>CDS<222>(1)..(3135)<220>
<221>mat_肽<222>(67)..(3135)<400>11
atg tgg aca ctg aag aga cta att ctt atc ctt ttt aac ata atc cta 48Met Trp Thr Leu Lys Arg Leu Ile Leu Ile Leu Phe Asn Ile Ile Leu-20 -15 -10att tcc aaa ctc ctt ggg gct aga tgg ttt cct aaa act ctg ccc tgt 96Ile Ser Lys Leu Leu Gly Ala Arg Trp Phe Pro Lys Thr Leu Pro Cys-5 -1 1 5 10gat gtc act ctg gat gtt cca aag aac cat gtg atc gtg gac tgc aca144Asp Val Thr Leu Asp Val Pro Lys Asn His Val Ile Val Asp Cys Thr15 20 25gac aag cat ttg aca gaa att cct gga ggt att ccc acg aac acc acg192Asp Lys His Leu Thr Glu Ile Pro Gly Gly Ile Pro Thr Asn Thr Thr30 35 40aac ctc acc ctc acc att aac cac ata cca gac atc tcc cca gcg tcc240Asn Leu Thr Leu Thr Ile Asn His Ile Pro Asp Ile Ser Pro Ala Ser45 50 55ttt cac aga ctg gac cat ctg gta gag atc gat ttc aga tgc aac tgt288Phe His Arg Leu Asp His Leu Val Glu Ile Asp Phe Arg Cys Asn Cys60 65 70gta cct att cca ctg ggg tca aaa aac aac atg tgc atc aag agg ctg336Val Pro Ile Pro Leu Gly Ser Lys Asn Asn Met Cys Ile Lys Arg Leu75 80 85 90cag att aaa ccc aga agc ttt agt gga ctc act tat tta aaa tcc ctt384Gln Ile Lys Pro Arg Ser Phe Ser Gly Leu Thr Tyr Leu Lys Ser Leu95 100 105tac ctg gat gga aac cag cta cta gag ata ccg cag ggc ctc ccg cct432Tyr Leu Asp Gly Asn Gln Leu Leu Glu Ile Pro Gln Gly Leu Pro Pro110 115 120agc tta cag ctt ctc agc ctt gag gcc aac aac atc ttt tcc atc aga480Ser Leu Gln Leu Leu Ser Leu Glu Ala Asn Asn Ile Phe Ser Ile Arg125 130 135aaa gag aat cta aca gaa ctg gcc aac ata gaa ata ctc tac ctg ggc528Lys Glu Asn Leu Thr Glu Leu Ala Asn Ile Glu Ile Leu Tyr Leu Gly140 145 150caa aac tgt tat tat cga aat cct tgt tat gtt tca tat tca ata gag576Gln Asn Cys Tyr Tyr Arg Asn Pro Cys Tyr Val Ser Tyr Ser Ile Glu155 160 165 170aaa gat gcc ttc cta aac ttg aca aag tta aaa gtg ctc tcc ctg aaa624Lys Asp Ala Phe Leu Asn Leu TAr Lys Leu Lys Val Leu Ser Leu Lys175 180 185gat aac aat gtc aca gcc gtc cct act gtt ttg cca tct act tta aca672Asp Asn Asn Val Thr Ala Val Pro Thr Val Leu Pro Ser Thr Leu Thr190 195 200gaa cta tat ctc tac aac aac atg att gca aaa atc caa gaa gat gat720
Glu Leu Tyr Leu Tyr Asn Asn Met Ile Ala Lys Ile Gln Glu Asp Asp205 210 215ttt aat aac ctc aac caa tta caa att ctt gac cta agt gga aat tgc768Phe Asn Asn Leu Asn Gln Leu Gln Ile Leu Asp Leu Ser Gly Asn Cys220 225 230cct cgt tgt tat aat gcc cca ttt cct tgt gcg ccg tgt aaa aat aat816Pro Arg Cys Tyr Asn Ala Pro Phe Pro Cys Ala Pro Cys Lys Asn Asn235 240 245 250tct ccc cta cag atc cct gta aat gct ttt gat gcg ctg aca gaa tta864Ser Pro Leu Gln Ile Pro Val Asn Ala Phe Asp Ala Leu Thr Glu Leu255 260 265aaa gtt tta cgt cta cac agt aac tct ctt cag cat gtg ccc cca aga912Lys Val Leu Arg Leu His Ser Asn Ser Leu Gln His Val Pro Pro Arg270 275 280tgg ttt aag aac atc aac aaa ctc cag gaa ctg gat ctg tcc caa aac960Trp Phe Lys Asn Ile Asn Lys Leu Gln Glu Leu Asp Leu Ser Gln Asn285 290 295ttc ttg gcc aaa gaa att ggg gat gct aaa ttt ctg cat ttt ctc ccc 1008Phe Leu Ala Lys Glu Ile Gly Asp Ala Lys Phe Leu His Phe Leu Pro300 305 310agc ctc atc caa ttg gat ctg tct ttc aat ttt gaa ctt cag gtc tat 1056Ser Leu Ile Gln Leu Asp Leu Ser Phe Asn Phe Glu Leu Gln Val Tyr315 320 325 330cgt gca tct atg aat cta tca caa gca ttt tct tca ctg aaa agc ctg 1104Arg Ala Ser Met Asn Leu Ser Gln Ala Phe Ser Ser Leu Lys Ser Leu335 340 345aaa att ctg cgg atc aga gga tat gtc ttt aaa gag ttg aaa agc ttt 1152Lys Ile Leu Arg Ile Arg Gly Tyr Val Phe Lys Glu Leu Lys Ser Phe350 355 360aac ctc tcg cca tta cat aat ctt caa aat ctt gaa gtt ctt gat ctt 1200Asn Leu Ser Pro Leu His Asn Leu Gln Asn Leu Glu Val Leu Asp Leu365 370 375ggc act aac ttt ata aaa att gct aac ctc agc atg ttt aaa caa ttt 1248Gly Thr Asn Phe Ile Lys Ile Ala Asn Leu Ser Met Phe Lys Gln Phe380 385 390aaa aga ctg aaa gtc ata gat ctt tca gtg aat aaa ata tca cct tca 1296Lys Arg Leu Lys Val Ile Asp Leu Ser Val Asn Lys Ile Ser Pro Ser395 400 405 410gga gat tca agt gaa gtt ggc ttc tgc tca aat gcc aga act tct gta 1344Gly Asp Ser Ser Glu Val Gly Phe Cys Ser Asn Ala Arg Thr Ser Val415 420 425gaa agt tat gaa ccc cag gtc ctg gaa caa tta cat tat ttc aga tat 1392Glu Ser Tyr Glu Pro Gln Val Leu Glu Gln Leu His Tyr Phe Arg Tyr
430 435 440gat aag tat gca agg agt tgc aga ttc aaa aac aaa gag gct tct ttc1440Asp Lys Tyr Ala Arg Ser Cys Arg Phe Lys Asn Lys Glu Ala Ser Phe445 450 455atg tct gtt aat gaa agc tgc tac aag tat ggg cag acc ttg gat cta1488Met Ser Val Asn Glu Ser Cys Tyr Lys Tyr Gly Gln Thr Leu Asp Leu460 465 470agt aaa aat agt ata ttt ttt gtc aag tcc tct gat ttt cag cat ctt1536Ser Lys Asn Ser Ile Phe Phe Val Lys Ser Ser Asp Phe Gln His Leu475 480 485 490tct ttc ctc aaa tgc ctg aat ctg tca gga aat ctc att agc caa act1584Ser Phe Leu Lys Cys Leu Asn Leu Ser Gly Asn Leu Ile Ser Gln Thr495 500 505ctt aat ggc agt gaa ttc caa cct tta gca gag ctg aga tat ttg gac1632Leu Asn Gly Ser Glu Phe Gln Pro Leu Ala Glu Leu Arg Tyr Leu Asp510 515 520ttc tcc aac aac cgg ctt gat tta ctc cat tca aca gca ttt gaa gag1680Phe Ser Asn Asn Arg Leu Asp Leu Leu His Ser Thr Ala Phe Glu Glu525 530 535ctt cac aaa ctg gaa gtt ctg gat ata agc agt aat agc cat tat ttt1728Leu His Lys Leu Glu Val Leu Asp Ile Ser Ser Asn Ser His Tyr Phe540 545 550caa tca gaa gga att act cat atg cta aac ttt acc aag aac cta aag1776Gln Ser Glu Gly Ile Thr His Met Leu Asn Phe Thr Lys Asn Leu Lys555 560 565 570gtt ctg cag aaa ctg atg atg aac gac aat gac atc tct tcc tcc acc1824Val Leu Gln Lys Leu Met Met Asn Asp Asn Asp Ile Ser Ser Ser Thr575 580 585agc agg acc atg gag agt gag tct ctt aga act ctg gaa ttc aga gga1872Ser Arg Thr Met Glu Ser Glu Ser Leu Arg Thr Leu Glu Phe Arg Gly590 595 600aat cac tta gat gtt tta tgg aga gaa ggt gat aac aga tac tta caa1920Asn His Leu Asp Val Leu Trp Arg Glu Gly Asp Asn Arg Tyr Leu Gln605 610 615tta ttc aag aat ctg cta aaa tta gag gaa tta gac atc tct aaa aat1968Leu Phe Lys Asn Leu Leu Lys Leu Glu Glu Leu Asp Ile Ser Lys Asn620 625 630Lcc cta agt ttc ttg cct tct gga gtt ttt gat ggt atg cct cca aat2016Ser Leu Ser Phe Leu Pro Ser Gly Val Phe Asp Gly Met Pro Pro Asn635 640 645 650cta aag aat ctc tct ttg gcc aaa aat ggg ctc aaa tct ttc agt tgg2064Leu Lys Asn Leu Ser Leu Ala Lys Asn Gly Leu Lys Ser Phe Ser Trp655 660 665
aag aaa ctc cag tgt cta aag aac ctg gaa act ttg gac ctc agc cac2112Lys Lys Leu Gln Cys Leu Lys Asn Leu Glu Thr Leu Asp Leu Ser His670 675 680aac caa ctg acc act gtc cct gag aga tta tcc aac tgt tcc aga agc2160Asn Gln Leu Thr Thr Val Pro Glu Arg Leu Ser Asn Cys Ser Arg Ser685 690 695ctc aag aat ctg att ctt aag aat aat caa atc agg agt ctg acg aag2208Leu Lys Asn Leu Ile Leu Lys Asn Asn Gln Ile Arg Ser Leu Thr Lys700 705 710tat ttt cta caa gat gcc ttc cag ttg cga tat ctg gat ctc agc tca2256Tyr Phe Leu Gln Asp Ala Phe Gln Leu Arg Tyr Leu Asp Leu Ser Ser715 720 725 730aat aaa atc cag atg atc caa aag acc agc ttc cca gaa aat gtc ctc2304Asn Lys Ile Gln Met Ile Gln Lys Thr Ser Phe Pro Glu Asn Val Leu735 740 745aac aat ctg aag atg ttg ctt ttg cat cat aat cgg ttt ctg tgc acc2352Asn Asn Leu Lys Met Leu Leu Leu His His Asn Arg Phe Leu Cys Thr750 755 760tgt gat gct gtg tgg ttt gtc tgg tgg gtt aac cat acg gag gtg act2400Cys Asp Ala Val Trp Phe Val Trp Trp Val Asn His Thr Glu Val Thr765 770 775att cct tac ctg gcc aca gat gtg act tgt gtg ggg cca gga gca cac2448Ile Pro Tyr Leu Ala Thr Asp Val Thr Cys Val Gly Pro Gly Ala His780 785 790aag ggc caa agt gtg atc tcc ctg gat ctg tac acc tgt gag tta gat2496Lys Gly Gln Ser Val Ile Ser Leu Asp Leu Tyr Thr Cys Glu Leu Asp795 800 805 810ctg act aac ctg att ctg ttc tca ctt tcc ata tct gta tct ctc ttt2544Leu Thr Asn Leu Ile Leu Phe Ser Leu Ser Ile Ser Val Ser Leu Phe815 820 825ctc atg gtg atg atg aca gca agt cac ctc tat ttc tgg gat gtg tgg2592Leu Met Val Met Met Thr Ala Ser His Leu Tyr Phe Trp Asp Val Trp830 835 840tat att tac cat ttc tgt aag gcc aag ata aag ggg tat cag cgt cta2640Tyr Ile Tyr His Phe Cys Lys Ala Lys Ile Lys Gly Tyr Gln Arg Leu845 850 855ata tca cca gac tgt tgc tat gat gct ttt att gtg tat gac act aaa2688Ile Ser Pro Asp Cys Cys Tyr Asp Ala Phe Ile Val Tyr Asp Thr Lys860 865 870gac cca gct gtg acc gag tgg gtt ttg gct gag ctg gtg gcc aaa ctg2736Asp Pro Ala Val Thr Glu Trp Val Leu Ala Glu Leu Val Ala Lys Leu875 880 885 890
gaa gac cca aga gag aaa cat ttt aat tta tgt ctc gag gaa agg gac2784Glu Asp Pro Arg Glu Lys His Phe Asn Leu Cys Leu Glu Glu Arg Asp895 900 905tgg tta cca ggg cag cca gtt ctg gaa aac ctt tcc cag agc ata cag2832Trp Leu Pro Gly Gln Pro Val Leu Glu Asn Leu Ser Gln Ser Ile Gln910 915 920ctt agc aaa aag aca gtg ttt gtg atg aca gac aag tat gca aag act2880Leu Ser Lys Lys Thr Val Phe Val Met Thr Asp Lys Tyr Ala Lys Thr925 930 935gaa aat ttt aag ata gca ttt tac ttg tcc cat cag agg ctc atg gat2928Glu Asn Phe Lys Ile Ala Phe Tyr Leu Ser His Gln Arg Leu Met Asp940 945 950gaa aaa gtt gat gtg att atc ttg ata ttt ctt gag aag ccc ttt cag2976Glu Lys Val Asp Val Ile Ile Leu Ile Phe Leu Glu Lys Pro Phe Gln955 960 965 970aag tcc aag ttc ctc cag ctc cgg aaa agg ctc tgt ggg agt tct gtc3024Lys Ser Lys Phe Leu Gln Leu Arg Lys Arg Leu Cys Gly Ser Ser Val975 980 985ctt gag tgg cca aca aac ccg caa gct cac cca tac ttc tgg cag tgt3072Leu Glu Trp Pro Thr Asn Pro Gln Ala His Pro Tyr Phe Trp Gln Cys990 995 1000cta aag aac gcc ctg gcc aca gac aat cat gtg gcc tat agt cag gtg3120Leu Lys Asn Ala Leu Ala Thr Asp Asn His Val Ala Tyr Ser Gln Val100510101015ttc aag gaa acg gtc tag3138Phe Lys Glu Thr Val1020<210>12<211>1045<212>PRT<213>未知<400>12Met Trp Thr Leu Lys Arg Leu Ile Leu Ile Leu Phe Asn Ile Ile Leu-20 -15 -10Ile Ser Lys Leu Leu Gly Ala Arg Trp Phe Pro Lys Thr Leu Pro Cys-5 -1 1 5 10Asp Val Thr Leu Asp Val Pro Lys Asn His Val Ile Val Asp Cys Thr15 20 25Asp Lys His Leu Thr Glu Ile Pro Gly Gly Ile Pro Thr Asn Thr Thr30 35 40Asn Leu Thr Leu Thr Ile Asn His Ile Pro Asp Ile Ser Pro Ala Ser45 50 55
Phe His Arg Leu Asp His Leu Val Glu Ile Asp Phe Arg Cys Asn Cys60 65 70Val Pro Ile Pro Leu Gly Ser Lys Asn Asn Met Cys Ile Lys Arg Leu75 80 85 90Gln Ile Lys Pro Arg Ser Phe Ser Gly Leu Thr Tyr Leu Lys Ser Leu95 100 105Tyr Leu Asp Gly Asn Gln Leu Leu Glu Ile Pro Gln Gly Leu Pro Pro110 115 120Ser Leu Gln Leu Leu Ser Leu Glu Ala Asn Asn Ile Phe Ser Ile Arg125 130 135Lys Glu Asn Leu Thr Glu Leu Ala Asn Ile Glu Ile Leu Tyr Leu Gly140 145 150Gln Asn Cys Tyr Tyr Arg Asn Pro Cys Tyr Val Ser Tyr Ser Ile Glu155 160 165 170Lys Asp Ala Phe Leu Asn Leu Thr Lys Leu Lys Val Leu Ser Leu Lys175 180 185Asp Asn Asn Val Thr Ala Val Pro Thr Val Leu Pro Ser Thr Leu Thr190 195 200Glu Leu Tyr Leu Tyr Asn Asn Met Ile Ala Lys Ile Gln Glu Asp Asp205 210 215Phe Asn Asn Leu Asn Gln Leu Gln Ile Leu Asp Leu Ser Gly Asn Cys220 225 230Pro Arg Cys Tyr Asn Ala Pro Phe Pro Cys Ala Pro Cys Lys Asn Asn235 240 245 250Ser Pro Leu Gln Ile Pro Val Asn Ala Phe Asp Ala Leu Thr Glu Leu255 260 265Lys Val Leu Arg Leu His Ser Asn Ser Leu Gln His Val Pro Pro Arg270 275 280Trp Phe Lys Asn Ile Asn Lys Leu Gln Glu Leu Asp Leu Ser Gln Asn285 290 295Phe Leu Ala Lys Glu Ile Gly Asp Ala Lys Phe Leu His Phe Leu Pro300 305 310Ser Leu Ile Gln Leu Asp Leu Ser Phe Asn Phe Glu Leu Gln Val Tyr315 320 325 330Arg Ala Ser Met Asn Leu Ser Gln Ala Phe Ser Ser Leu Lys Ser Leu335 340 345Lys Ile Leu Arg Ile Arg Gly Tyr Val Phe Lys Glu Leu Lys Ser Phe350 355360
Asn Leu Ser Pro Leu His Asn Leu Gln Asn Leu Glu Val Leu Asp Leu365 370 375Gly Thr Asn Phe Ile Lys Ile Ala Asn Leu Ser Met Phe Lys Gln Phe380 385 390Lys Arg Leu Lys Val Ile Asp Leu Ser Val Asn Lys Ile Ser Pro Ser395 400 405 410Gly Asp Ser Ser Glu Val Gly Phe Cys Ser Asn Ala Arg Thr Ser Val415 420 425Glu Ser Tyr Glu Pro Gln Val Leu Glu Gln Leu His Tyr Phe Arg Tyr430 435 440Asp Lys Tyr Ala Arg Ser Cys Arg Phe Lys Asn Lys Glu Ala Ser Phe445 450 455Met Ser Val Asn Glu Ser Cys Tyr Lys Tyr Gly Gln Thr Leu Asp Leu460 465 470Ser Lys Asn Ser Ile Phe Phe Val Lys Ser Ser Asp Phe Gln His Leu475 480 485 490Ser Phe Leu Lys Cys Leu Asn Leu Ser Gly Asn Leu Ile Ser Gln Thr495 500 505Leu Asn Gly Ser Glu Phe Gln Pro Leu Ala Glu Leu Arg Tyr Leu Asp510 515 520Phe Ser Asn Asn Arg Leu Asp Leu Leu His Ser Thr Ala Phe Glu Glu525 530 535Leu His Lys Leu Glu Val Leu Asp Ile Ser Ser Asn Ser His Tyr Phe540 545 550Gln Ser Glu Gly Ile Thr His Met Leu Asn Phe Thr Lys Asn Leu Lys555 560 565 570Val Leu Gln Lys Leu Met Met Asn Asp Asn Asp Ile Ser Ser Ser Thr575 580 585Ser Arg Thr Met Glu Ser Glu Ser Leu Arg Thr Leu Glu Phe Arg Gly590 595 600Asn His Leu Asp Val Leu Trp Arg Glu Gly Asp Asn Arg Tyr Leu Gln605 610 615Leu Phe Lys Asn Leu Leu Lys Leu Glu Glu Leu Asp Ile Ser Lys Asn620 625 630Ser Leu Ser Phe Leu Pro Ser Gly Val Phe Asp Gly Met Pro Pro Asn635 640 645 650Leu Lys Asn Leu Ser Leu Ala Lys Asn Gly Leu Lys Ser Phe Ser Trp655 660 665
Lys Lys Leu Gln Cys Leu Lys Asn Leu Glu Thr Leu Asp Leu Ser His670 675 680Asn Gln Leu Thr Thr Val Pro Glu Arg Leu Ser Asn Cys Ser Arg Ser685 690 695Leu Lys Asn Leu Ile Leu Lys Asn Asn Gln Ile Arg Ser Leu Thr Lys700 705 710Tyr Phe Leu Gln Asp Ala Phe Gln Leu Arg Tyr Leu Asp Leu Ser Ser715 720 725 730Asn Lys Ile Gln Met Ile Gln Lys Thr Ser Phe Pro Glu Asn Val Leu735 740 745Asn Asn Leu Lys Met Leu Leu Leu His His Asn Arg Phe Leu Cys Thr750 755 760Cys Asp Ala Val Trp Phe Val Trp Trp Val Asn His Thr Glu Val Thr765 770 775Ile Pro Tyr Leu Ala Thr Asp Val Thr Cys Val Gly Pro Gly Ala His780 785 790Lys Gly Gln Ser Val Ile Ser Leu Asp Leu Tyr Thr Cys Glu Leu Asp795 800 805 810Leu Thr Asn Leu Ile Leu Phe Ser Leu Ser Ile Ser Val Ser Leu Phe815 820 825Leu Met Val Met Met Thr Ala Ser His Leu Tyr Phe Trp Asp Val Trp830 835 840Tyr Ile Tyr His Phe Cys Lys Ala Lys Ile Lys Gly Tyr Gln Arg Leu845 850 855Ile Ser Pro Asp Cys Cys Tyr Asp Ala Phe Ile Val Tyr Asp Thr Lys860 865 870Asp Pro Ala Val Thr Glu Trp Val Leu Ala Glu Leu Val Ala Lys Leu875 880 885 890Glu Asp Pro Arg Glu Lys His Phe Asn Leu Cys Leu Glu Glu Arg Asp895 900 905Trp Leu Pro Gly Gln Pro Val Leu Glu Asn Leu Ser Gln Ser Ile Gln910 915 920Leu Ser Lys Lys Thr Val Phe Val Met Thr Asp Lys Tyr Ala Lys Thr925 930 935Glu Asn Phe Lys Ile Ala Phe Tyr Leu Ser His Gln Arg Leu Met Asp940 945 950Glu Lys Val Asp Val Ile Ile Leu Ile Phe Leu Glu Lys Pro Phe Gln955 960 965 970
Lys Ser Lys Phe Leu Gln Leu Arg Lys Arg Leu Cys Gly Ser Ser Val975 980 985Leu Glu Trp Pro Thr Asn Pro Gln Ala His Pro Tyr Phe Trp Gln Cys990 995 1000Leu Lys Asn Ala Leu Ala Thr Asp Asn His Val Ala Tyr Ser Gln Val100510101015Phe Lys Glu Thr Val1020<210>13<211>180<212>DNA<213>未知<220>
<223>未知生物的说明啮齿类动物；推测为小鼠(Mus musculus)<220>
<221>CDS<222>(1)..(177)<400>13ctt gga aaa cct ctt cag aag tct aag ttt ctt cag ctc agg aag aga 48Leu Gly Lys Pro Leu Gln Lys Ser Lys Phe Leu Gln Leu Arg Lys Arg1 5 10 15ctc tgc agg agc tct gtc ctt gag tgg cct gca aat cca cag gct cac 96Leu Cys Arg Ser Ser Val Leu Glu Trp Pro Ala Asn Pro Gln Ala His20 25 30cca tac ttc tgg cag tgc ctg aaa aat gcc ctg acc aca gac aat cat144Pro Tyr Phe Trp Gln Cys Leu Lys Asn Ala Leu Thr Thr Asp Asn His35 40 45gtg gct tat agt caa atg ttc aag gaa aca gtc tag180Val Ala Tyr Ser Gln Met Phe Lys Glu Thr Val50 55<210>14<211>59<212>PRT<213>未知<400>14Leu Gly Lys Pro Leu Gln Lys Ser Lys Phe Leu Gln Leu Arg Lys Arg1 5 10 15Leu Cys Arg Ser Ser Val Leu Glu Trp Pro Ala Asn Pro Gln Ala His20 25 30
Pro Tyr Phe Trp Gln Cys Leu Lys Asn Ala Leu Thr Thr Asp Asn His35 40 45Val Ala Tyr Ser Gln Met Phe Lys Glu Thr Val50 55<210>15<211>990<212>DNA<213>未知<220>
<223>未知生物的说明灵长类动物；推测为人(Homo sapiens)<220>
<221>CDS<222>(2)..(988)<400>15g aat tcc aga ctt ata aac ttg aaa aat ctc tat ttg gcc tgg aac tgc 49Asn Ser Arg Leu Ile Asn Leu Lys Asn Leu Tyr Leu Ala Trp Asn Cys1 5 10 15tat ttt aac aaa gtt tgc gag aaa act aac ata gaa gat gga gta ttt 97Tyr Phe Asn Lys Val Cys Glu Lys Thr Asn Ile Glu Asp Gly Val Phe20 25 30gaa acg ctg aca aat ttg gag ttg cta tca cta tct ttc aat tct ctt145Glu Thr Leu Thr Asn Leu Glu Leu Leu Ser Leu Ser Phe Asn Ser Leu35 40 45tca cat gtg cca ccc aaa ctg cca agc tcc cta cgc aaa ctt ttt ctg193Ser His Val Pro Pro Lys Leu Pro Ser Ser Leu Arg Lys Leu Phe Leu50 55 60agc aac acc cag atc aaa tac att agt gaa gaa gat ttc aag gga ttg241Ser Asn Thr Gln Ile Lys Tyr Ile Ser Glu Glu Asp Phe Lys Gly Leu65 70 75 80ata aat tta aca tta cta gat tta agc ggg aac tgt ccg agg tgc ttc289Ile Asn Leu Thr Leu Leu Asp Leu Ser Gly Asn Cys Pro Arg Cys Phe85 90 95aat gcc cca ttt cca tgc gtg cct tgt gat ggt ggt gct tca att aat337Asn Ala Pro Phe Pro Cys Val Pro Cys Asp Gly Gly Ala Ser Ile Asn100 105 110ata gat cgt ttt gct ttt caa aac ttg acc caa ctt cga tac cta aac385Ile Asp Arg Phe Ala Phe Gln Asn Leu Thr Gln Leu Arg Tyr Leu Asn115 120 125ctc tct agc act tcc ctc agg aag att aat gct gcc tgg ttt aaa aat433Leu Ser Ser Thr Ser Leu Arg Lys Ile Asn Ala Ala Trp Phe Lys Asn
130 135 140atg cct cat ctg aag gtg ctg gat ctt gaa ttc aac tat tta gtg gga481Met Pro His Leu Lys Val Leu Asp Leu Glu Phe Asn Tyr Leu Val Gly145 150 155 160gaa ata gcc tct ggg gca ttt tta acg atg ctg ccc cgc tta gaa ata529Glu Ile Ala Ser Gly Ala Phe Leu Thr Met Leu Pro Arg Leu Glu Ile165 170 175ctt gac ttg tct ttt aac tat ata aag ggg agt tat cca cag cat att577Leu Asp Leu Ser Phe Asn Tyr Ile Lys Gly Ser Tyr Pro Gln His Ile180 185 190aat att tcc aga aac ttc tct aaa ctt ttg tct cta cgg gca ttg cat625Asn Ile Ser Arg Asn Phe Ser Lys Leu Leu Ser Leu Arg Ala Leu His195 200 205tta aga ggt tat gtg ttc cag gaa ctc aga gaa gat gat ttc cag ccc673Leu Arg Gly Tyr Val Phe Gln Glu Leu Arg Glu Asp Asp Phe Gln Pro210 215 220ctg atg cag ctt cca aac tta tcg act atc aac ttg ggt att aat ttt721Leu Met Gln Leu Pro Asn Leu Ser Thr Ile Asn Leu Gly Ile Asn Phe225 230 235 240att aag caa atc gat ttc aaa ctt ttc caa aat ttc tcc aat ctg gaa769Ile Lys Gln Ile Asp Phe Lys Leu Phe Gln Asn Phe Ser Asn Leu Glu245 250 255att att tac ttg tca gaa aac aga ata tca ccg ttg gta aaa gat acc817Ile Ile Tyr Leu Ser Glu Asn Arg Ile Ser Pro Leu Val Lys Asp Thr260 265 270cgg cag agt tat gca aat agt tcc tct ttt caa cgt cat atc cgg aaa865Arg Gln Ser Tyr Ala Asn Ser Ser Ser Phe Gln Arg His Ile Arg Lys275 280 285cga cgc tca aca gat ttt gag ttt gac cca cat tcg aac ttt tat cat913Arg Arg Ser Thr Asp Phe Glu Phe Asp Pro His Ser Asn Phe Tyr His290 295 300ttc acc cgt cct tta ata aag cca caa tgt gct gct tat gga aaa gcc961Phe Thr Arg Pro Leu Ile Lys Pro Gln Cys Ala Ala Tyr Gly Lys Ala305 310 315 320tta gat tta agc ctc aac agt att ttc tt 990Leu Asp Leu Ser Leu Asn Ser Ile Phe325<210>16<211>329<212>PRT<213>未知<400>16
Asn Ser Arg Leu Ile Asn Leu Lys Asn Leu Tyr Leu Ala Trp Asn Cys1 5 10 15Tyr Phe Asn Lys Val Cys Glu Lys Thr Asn Ile Glu Asp Gly Val Phe20 25 30Glu Thr Leu Thr Asn Leu Glu Leu Leu Ser Leu Ser Phe Asn Ser Leu35 40 45Ser His Val Pro Pro Lys Leu Pro Ser Ser Leu Arg Lys Leu Phe Leu50 55 60Ser Asn Thr Gln Ile Lys Tyr Ile Ser Glu Glu Asp Phe Lys Gly Leu65 70 75 80Ile Asn Leu Thr Leu Leu Asp Leu Ser Gly Asn Cys Pro Arg Cys Phe85 90 95Asn Ala Pro Phe Pro Cys Val Pro Cys Asp Gly Gly Ala Ser Ile Asn100 105 110Ile Asp Arg Phe Ala Phe Gln Asn Leu Thr Gln Leu Arg Tyr Leu Asn115 120 125Leu Ser Ser Thr Ser Leu Arg Lys Iie Asn Ala Ala Trp Phe Lys Asn130 135 140Met Pro His Leu Lys Val Leu Asp Leu Glu Phe Asn Tyr Leu Val Gly145 150 155 160Glu Ile Ala Ser Gly Ala Phe Leu Thr Met Leu Pro Arg Leu Glu Ile165 170 175Leu Asp Leu Ser Phe Asn Tyr Ile Lys Gly Ser Tyr Pro Gln His Ile180 185 190Asn Ile Ser Arg Asn Phe Ser Lys Leu Leu Ser Leu Arg Ala Leu His195 200 205Leu Arg Gly Tyr Val Phe Gln Glu Leu Arg Glu Asp Asp Phe Gln Pro210 215 220Leu Met Gln Leu Pro Asn Leu Ser Thr Ile Asn Leu Gly Ile Asn Phe225 230 235 240Ile Lys Gln Ile Asp Phe Lys Leu Phe Gln Asn Phe Ser Asn Leu Glu245 250 255Ile Ile Tyr Leu Ser Glu Asn Arg Ile Ser Pro Leu Val Lys Asp Thr260 265 270Arg Gln Ser Tyr Ala Asn Ser Ser Ser Phe Gln Arg His Ile Arg Lys275 280 285Arg Arg Ser Thr Asp Phe Glu Phe Asp Pro His Ser Asn Phe Tyr His290 295 300
Phe Thr Arg Pro Leu Ile Lys Pro Gln Cys Ala Ala Tyr Gly Lys Ala305 310 315 320Leu Asp Leu Ser Leu Asn Ser Ile Phe325<210>17<211>1557<212>DNA<213>未知<220>
<223>未知生物的说明灵长类动物；推测为人(Homo sapiells)<220>
<221>CDS<222>(1)..(513)<220>
<221>misc_特征<222>(93)..(149)<223>Xaa翻译取决于遗传密码<400>17cag tct ctt tcc aca tcc caa act ttc tat gat gct tac att tct tat 48Gln Ser Leu Ser Thr Ser Gln Thr Phe Tyr Asp Ala Tyr Ile Ser Tyr15 10 15gac acc aaa gat gcc tct gtt act gac tgg gtg ata aat gag ctg cgc 96Asp Thr Lys Asp Ala Ser Val Thr Asp Trp Val Ile Asn Glu Leu Arg20 25 30tac cac ctt gaa gag agc cga gac aaa aac gtt ctc ctt tgt cta gag144Tyr His Leu Glu Glu Ser Arg Asp Lys Asn Val Leu Leu Cys Leu Glu35 40 45gag agg gat tgg gac ccg gga ttg gcc atc atc gac aac ctc atg cag192Glu Arg Asp Trp Asp Pro Gly Leu Ala Ile Ile Asp Asn Leu Met Gln50 55 60agc atc aac caa agc aag aaa aca gta ttt gtt tta acc aaa aaa tat240Ser Ile Asn Gln Ser Lys Lys Thr Val Phe Val Leu Thr Lys Lys Tyr65 70 75 80gca aaa agc tgg aac ttt aaa aca gct ttt tac ttg gsc ttg cag agg288Ala Lys Ser Trp Asn Phe Lys Thr Ala Phe Tyr Leu Xaa Leu Gln Arg85 90 95cta atg ggt gag aac atg gat gtg att ata ttt atc ctg ctg gag cca336Leu Met Gly Glu Asn Met Asp Val Ile Ile Phe Ile Leu Leu Glu Pro100 105 110gtg tta cag cat tct ccg tat ttg agg cta cgg cag cgg atc tgt aag384Val Leu Gln His Ser Pro Tyr Leu Arg Leu Arg Gln Arg Ile Cys Lys
115 120 125agc tcc atc ctc cag tgg cct gac aac ccg aag gca gaa agg ttg ttt432Ser Ser Ile Leu Gln Trp Pro Asp Asn Pro Lys Ala Glu Arg Leu Phe130 135 140tgg caa act ctg wga aat gtg gtc ttg act gaa aat gat tca cgg tat480Trp Gln Thr Leu Xaa Asn Val Val Leu Thr Glu Asn Asp Ser Arg Tyr145 150 155 160aac aat atg tat gtc gat tcc att aag caa tac taactgacgt taagtcatga 533Asn Asn Met Tyr Val Asp Ser Ile Lys Gln Tyr165 170tttcgcgcca taataaagat gcaaaggaat gacatttcng tattagttat ctattgctan 593ggtaacnaaa ttantcccaa aaancttang tnggtttnaa aacaacnaca ttntgctggn 653cccacagttt ttgagggtca ggagtccagg cccagcataa ctgggtcttc tgcttcaggg 713tgtctncaga ggctgcaatg taggtgttca ccagagacat aggcatcact ggggtcacac 773tncatgtggt tgttttctgg attcaattcc tcctgggcta ttggccaaag gctatactca 833tgtaagccat gcgagcctat cccacaangg cagcttgctt catcagagct agcaaaaaag 893agaggttgct agcaagatga agtcacaatc ttttgtaatc gaatcaaaaa agtgatatct 953catcactttg gccatattct atttgttaga agtaaaccac aggtcccacc agctccatgg 1013gagtgaccac ctcagtccag ggaaaacagc tgaagaccaa gatggtgagc tctgattgct 1073tcagttggtc atcaactatt ttcccttgac tgctgtcctg ggatggccgg ctatcttgat 1133ggatagattg tgaatatcag gaggccaggg atcactgtgg accatcttag cagttgacct 1193aacacatctt cttttcaata tctaagaact tttgccactg tgactaatgg tcctaatatt 1253aagctgttgt ttatatttat catatatcta tggctacatg gttatattat gctgtggttg 1313cgttcggttt tatttacagt tgcttttaca aatatttgct gtaacatttg acttctaagg 1373tttagatgcc atttaagaac tgagatggat agcttttaaa gcatctttta cttcttacca 1433ttttttaaaa gtatgcagct aaattcgaag cttttggtct atattgttaa ttgccattgc 1493tgtaaatctt aaaatgaatg aataaaaatg tttcatttta aaaaaaaaaa aaaaaaaaaa 1553aaaa 1557<210>18<211>171<212>PRT<213>未知<400>18
Gln Ser Leu Ser Thr Ser Gln Thr Phe Tyr Asp Ala Tyr Ile Ser Tyr1 5 10 15Asp Thr Lys Asp Ala Ser Val Thr Asp Trp Val Ile Asn Glu Leu Arg20 25 30Tyr His Leu Glu Glu Ser Arg Asp Lys Asn Val Leu Leu Cys Leu Glu35 40 45Glu Arg Asp Trp Asp Pro Gly Leu Ala Ile Ile Asp Asn Leu Met Gln50 55 60Ser Ile Asn Gln Ser Lys Lys Thr Val Phe Val Leu Thr Lys Lys Tyr65 70 75 80Ala Lys Ser Trp Asn Phe Lys Thr Ala Phe Tyr Leu Xaa Leu Gln Arg85 90 95Leu Met Gly Glu Asn Met Asp Val Ile Ile Phe Ile Leu Leu Glu Pro100 105 110Val Leu Gln His Ser Pro Tyr Leu Arg Leu Arg Gln Arg Ile Cys Lys115 120 125Ser Ser Ile Leu Gln Trp Pro Asp Asn Pro Lys Ala Glu Arg Leu Phe130 135 140Trp Gln Thr Leu Xaa Asn Val Val Leu Thr Glu Asn Asp Ser Arg Tyr145 150 155 160Asn Asn Met Tyr Val Asp Ser Ile Lys Gln Tyr165 170<210>19<211>629<212>DNA<213>未知<220>
<223>未知生物的说明灵长类动物；推测为人(Homo sapiens)<220>
<221>CDS<222>(1)..(486)<220>
<221>misc_特征<222>(48)..(75)<223>Xaa翻译取决于遗传密码<400>19aat gaa ttg atc ccc aat cta gag aag gaa gat ggt tct atc ttg att48Asn Glu Leu Ile Pro Asn Leu Glu Lys Glu Asp Gly Ser Ile Leu Ile1 5 10 15
tgc ctt tat gaa agc tac ttt gac cct ggc aaa agc att agt gaa aat 96Cys Leu Tyr Glu Ser Tyr Phe Asp Pro Gly Lys Ser Ile Ser Glu Asn20 25 30att gta agc ttc att gag aaa agc tat aag tcc atc ttt gtt ttg tcy144Ile Val Ser Phe Ile Glu Lys Ser Tyr Lys Ser Ile Phe Val Leu Xaa35 40 45ccc aac ttt gtc cag aat gag tgg tgc cat tat gaa ttc tac ttt gcc192Pro Asn Phe Val Gln Asn Glu Trp Cys His Tyr Glu Phe Tyr Phe Ala50 55 60cac cac aat ctc ttc cat gaa aat tct gat cay ata att ctt atc tta240His His Asn Leu Phe His Glu Asn Ser Asp Xaa Ile Ile Leu Ile Leu65 70 75 80ctg gaa ccc att cca ttc tat tgc att ccc acc agg tat cat aaa ctg288Leu Glu Pro Ile Pro Phe Tyr Cys Ile Pro Thr Arg Tyr His Lys Leu85 90 95gaa gct ctc ctg gaa aaa aaa gca tac ttg gaa tgg ccc aag gat agg336Glu Ala Leu Leu Glu Lys Lys Ala Tyr Leu Glu Trp Pro Lys Asp Arg100 105 110cgt aaa tgt ggg ctt ttc tgg gca aac ctt cga gct gct gtt aat gtt384Arg Lys Cys Gly Leu Phe Trp Ala Asn Leu Arg Ala Ala Val Asn Val115 120 125aat gta tta gcc acc aga gaa atg tat gaa ctg cag aca ttc aca gag432Asn Val Leu Ala Thr Arg Glu Met Tyr Glu Leu Gln Thr Phe Thr Glu130 135 140tta aat gaa gag tct cga ggt tct aca atc tct ctg atg aga aca gac480Leu Asn Glu Glu Ser Arg Gly Ser Thr Ile Ser Leu Met Arg Thr Asp145 150 155 160tgt cta taaaatccca cagtccttgg gaagttgggg accacataca ctgttgggat 536Cys Leugtacattgat acaaccttta tgatggcaat ttgacaatat ttattaaaat aaaaaatggt 596tattcccttc aaaaaaaaaa aaaaaaaaaa aaa 629<210>20<211>162<212>PRT<213>未知<400>20Asn Glu Leu Ile Pro Asn Leu Glu Lys Glu Asp Gly Ser Ile Leu Ile1 5 10 15Cys Leu Tyr Glu Ser Tyr Phe Asp Pro Gly Lys Ser Ile Ser Glu Asn20 25 30
Ile Val Ser Phe Ile Glu Lys Ser Tyr Lys Ser Ile Phe Val Leu Xaa35 40 45Pro Asn Phe Val Gln Asn Glu Trp Cys His Tyr Glu Phe Tyr Phe Ala50 55 60His His Asn Leu Phe His Glu Asn Ser Asp Xaa Ile Ile Leu Ile Leu65 70 75 80Leu Glu Pro Ile Pro Phe Tyr Cys Ile Pro Thr Arg Tyr His Lys Leu85 90 95Glu Ala Leu Leu Glu Lys Lys Ala Tyr Leu Glu Trp Pro Lys Asp Arg100 105 110Arg Lys Cys Gly Leu Phe Trp Ala Asn Leu Arg Ala Ala Val Asn Val115 120 125Asn Val Leu Ala Thr Arg Glu Met Tyr Glu Leu Gln Thr Phe Thr Glu130 135 140Leu Asn Glu Glu Ser Arg Gly Ser Thr Ile Ser Leu Met Arg Thr Asp145 150 155 160Cys Leu<210>21<211>427<212>DNA<213>未知<220>
<223>未知生物的说明灵长类动物；推测为人(Homo sapiens)<220>
<221>CDS<222>(1)..(426)<400>21aag aac tcc aaa gaa aac ctc cag ttt cat gct ttt att tca tat agt 48Lys Asn Ser Lys Glu Asn Leu Gln Phe His Ala Phe Ile Ser Tyr Ser1 5 10 15gaa cat gat tct gcc tgg gtg aaa agt gaa ttg gta cct tac cta gaa 96Glu His Asp Ser Ala Trp Val Lys Ser Glu Leu Val Pro Tyr Leu Glu20 25 30aaa gaa gat ata cag att tgt ctt cat gag aga aac ttt gtc cct ggc144Lys Glu Asp Ile Gln Ile Cys Leu His Glu Arg Asn Phe Val Pro Gly35 40 45aag agc att gtg gaa aat atc atc aac tgc att gag aag agt tac aag192Lys Ser Ile Val Glu Asn Ile Ile Asn Cys Ile Glu Lys Ser Tyr Lys
50 55 60tcc atc ttt gtt ttg tct ccc aac ttt gtc cag agt gag tgg tgc cat240Ser Ile Phe Val Leu Ser Pro Asn Phe Val Gln Ser Glu Trp Cys His65 70 75 80tac gaa ctc tat ttt gcc cat cac aat ctc ttt cat gaa gga tct aat288Tyr Glu Leu Tyr Phe Ala His His Asn Leu Phe His Glu Gly Ser Asn85 90 95aac tta atc ctc atc tta ctg gaa ccc att cca cag aac agc att ccc336Asn Leu Ile Leu Ile Leu Leu Glu Pro Ile Pro Gln Asn Ser Ile Pro100 105 110aac aag tac cac aag ctg aag gct ctc atg acg cag cgg act tat ttg384Asn Lys Tyr His Lys Leu Lys Ala Leu Met Thr Gln Arg Thr Tyr Leu115 120 125cag tgg ccc aag gag aaa agc aaa cgt ggg ctc ttt tgg gct a 427Gln Trp Pro Lys Glu Lys Ser Lys Arg Gly Leu Phe Trp Ala130 135 140<210>22<211>142<212>PRT<213>未知<400>22Lys Asn Ser Lys Glu Asn Leu Gln Phe His Ala Phe Ile Ser Tyr Ser1 5 10 15Glu His Asp Ser Ala Trp Val Lys Ser Glu Leu Val Pro Tyr Leu Glu20 25 30Lys Glu Asp Ile Gln Ile Cys Leu His Glu Arg Asn Phe Val Pro Gly35 40 45Lys Ser Ile Val Glu Asn Ile Ile Asn Cys Ile Glu Lys Ser Tyr Lys50 55 60Ser Ile Phe Val Leu Ser Pro Asn Phe Val Gln Ser Glu Trp Cys His65 70 75 80Tyr Glu Leu Tyr Phe Ala His His Asn Leu Phe His Glu Gly Ser Asn85 90 95Asn Leu Ile Leu Ile Leu Leu Glu Pro Ile Pro Gln Asn Ser Ile Pro100 105 110Asn Lys Tyr His Lys Leu Lys Ala Leu Met Thr Gln Arg Thr Tyr Leu115 120 125Gln Trp Pro Lys Glu Lys Ser Lys Arg Gly Leu Phe Trp Ala130 135 140
<210>23<211>662<212>DNA<213>未知<220>
<223>未知生物的说明灵长类动物；推测为人(Homo sapiens)<220>
<221>CDS<222>(1)..(627)<220>
<221>misc_特征<222>(18)..(136)<223>Xaa翻译取决于遗传密码<400>23gct tcc acc tgt gcc tgg cct ggc ttc cct ggc ggg ggc ggc aaa gtg 48Ala Ser Thr Cys Ala Trp Pro Gly Phe Pro Gly Gly Gly Gly Lys Val1 5 10 15ggc gar atg agg atg ccc tgc cct acg atg cct tcg tgg tct tcg aca 96Gly Xaa Met Arg Met Pro Cys Pro Thr Met Pro Ser Trp Ser Ser Thr20 25 30aaa cgc rga gcg cag tgg cag act ggg tgt aca acg agc ttc ggg ggc144Lys Arg Xaa Ala Gln Trp Gln Thr Gly Cys Thr Thr Ser Phe Gly Gly35 40 45agc tgg agg agt gcc gtg ggc gct ggg cac tcc gcc tgt gcc tgg agg192Ser Trp Arg Ser Ala Val Gly Ala Gly His Ser Ala Cys Ala Trp Arg50 55 60aac gcg act ggc tgc ctg gca aaa ccc tct ttg aga acc tgt ggg cct240Asn Ala Thr Gly Cys Leu Ala Lys Pro Ser Leu Arg Thr Cys Gly Pro65 70 75 80cgg tct atg gca gcc gca aga cgc tgt ttg tgc tgg ccc aca cgg acc288Arg Ser Met Ala Ala Ala Arg Arg Cys Leu Cys Trp Pro Thr Arg Thr85 90 95ggg tca gtg gtc tct tgc gcg cca ktt ntc ctg ctg gcc cag cag cgc336Gly Ser Val Val Ser Cys Ala Pro Xaa Xaa Leu Leu Ala Gln Gln Arg100 105 110ctg ctg gar gac cgc aag gac gtc gtg gtg ctg gtg atc cta ang cct384Leu Leu Xaa Asp Arg Lys Asp Val Val Val Leu Val Ile Leu Xaa Pro115 120 125gac ggc caa gcc tcc cga cta cnn gat gcg ctg acc agc gcc tct gcc432Asp Gly Gln Ala Ser Arg Leu Xaa Asp Ala Leu Thr Ser Ala Ser Ala130 135 140gcc aga gtg tcc tcc tct ggc ccc acc agc cca gtg gtc gcg cag ctt480
Ala Arg Val Ser Ser Ser Gly Pro Thr Ser Pro Val Val Ala Gln Leu145 150 155 160ctg agg cca gca tgc atg gcc ctg acc agg gac aac cac cac ttc tat528Leu Arg Pro Ala Cys Met Ala Leu Thr Arg Asp Asn His His Phe Tyr165 170 175aac cgg aac ttc tgc cag gga acc cac ggc cga ata gcc gtg agc cgg576Asn Arg Asn Phe Cys Gln Gly Thr His Gly Arg Ile Ala Val Ser Arg180 185 190aat cct gca cgg tgc cac ctc cac aca cac cta aca tat gcc tgc ctg624Asn Pro Ala Arg Cys His Leu His Thr His Leu Thr Tyr Ala Cys Leu195 200 205atc tgaccaacac atgctcgcca ccctcaccac acacc 662Ile<210>24<211>209<212>PRT<213>未知<400>24Ala Ser Thr Cys Ala Trp Pro Gly Phe Pro Gly Gly Gly Gly Lys Val1 5 10 15Gly Xaa Met Arg Met Pro Cys Pro Thr Met Pro Ser Trp Ser Ser Thr20 25 30Lys Arg Xaa Ala Gln Trp Gln Thr Gly Cys Thr Thr Ser Phe Gly Gly35 40 45Ser Trp Arg Ser Ala Val Gly Ala Gly His Ser Ala Cys Ala Trp Arg50 55 60Asn Ala Thr Gly Cys Leu Ala Lys Pro Ser Leu Arg Thr Cys Gly Pro65 70 75 80Arg Ser Met Ala Ala Ala Arg Arg Cys Leu Cys Trp Pro Thr Arg Thr85 90 95Gly Ser Val Val Ser Cys Ala Pro Xaa Xaa Leu Leu Ala Gln Gln Arg100 105 110Leu Leu Xaa Asp Arg Lys Asp Val Val Val Leu Val Ile Leu Xaa Pro115 120 125Asp Gly Gln Ala Ser Arg Leu Xaa Asp Ala Leu Thr Ser Ala Ser Ala130 135 140Ala Arg Val Ser Ser Ser Gly Pro Thr Ser Pro Val Val Ala Gln Leu145 150 155 160Leu Arg Pro Ala Cys Met Ala Leu Thr Arg Asp Asn His His Phe Tyr165 170 175
Asn Arg Asn Phe Cys Gln Gly Thr His Gly Arg Ile Ala Val Sar Arg180 185 190Asn Pro Ala Arg Cys His Leu His Thr His Leu Thr Tyr Ala Cys Leu195 200 205Ile<210>25<211>4865<212>DNA<213>未知<220>
<223>未知生物的说明灵长类动物；推测为人(Homo sapiens)<220>
<221>CDS<222>(107)..(2617)<220>
<221>mat_肽<222>(173)..(2617)<220>
<221>misc_特征<222>(189)<223>Xaa翻译取决于遗传密码<400>25aaaatactcc cttgcctcaa aaactgctcg gtcaaacggt gatagcaaac cacgcattca 60cagggccact gctgctcaca naascagtga ggatgatgcc aggatg atg tct gcc 115Met Ser Ala-20tcg cgc ctg gct ggg act ctg atc cca gcc atg gcc ttc ctc tcc tgc163Ser Arg Leu Ala Gly Thr Leu Ile Pro Ala Met Ala Phe Leu Ser Cys-15 -10 -5gtg aga cca gaa agc tgg gag ccc tgc gtg gag gtt cct aat att act211Val Arg Pro Glu Ser Trp Glu Pro Cys Val Glu Val Pro Asn Ile Thr-1 1 5 10tat caa tgc atg gag ctg aat ttc tac aaa atc ccc gac aac ctc ccc259Tyr Gln Cys Met Glu Leu Asn Phe Tyr Lys Ile Pro Asp Asn Leu Pro15 20 25ttc tca acc aag aac ctg gac ctg agc ttt aat ccc ctg agg cat tta307Phe Ser Thr Lys Asn Leu Asp Leu Ser Phe Asn Pro Leu Arg His Leu30 35 40 45
ggc agc tat agc ttc ttc agt ttc cca gaa ctg cag gtg ctg gat tta355Gly Ser Tyr Ser Phe Phe Ser Phe Pro Glu Leu Gln Val Leu Asp Leu50 55 60tcc agg tgt gaa atc cag aca att gaa gat ggg gca tat cag agc cta403Ser Arg Cys Glu Ile Gln Thr Ile Glu Asp Gly Ala Tyr Gln Ser Leu65 70 75agc cac ctc tct acc tta ata ttg aca gga aac ccc atc cag agt tta451Ser His Leu Ser Thr Leu Ile Leu Thr Gly Asn Pro Ile Gln Ser Leu80 85 90gcc ctg gga gcc ttt tct gga cta tca agt tta cag aag ctg gtg gct499Ala Leu Gly Ala Phe Ser Gly Leu Ser Ser Leu Gln Lys Leu Val Ala95 100 105gtg gag aca aat cta gca tct cta gag aac ttc ccc att gga cat ctc547Val Glu Thr Asn Leu Ala Ser Leu Glu Asn Phe Pro Ile Gly His Leu110 115 120 125aaa act ttg aaa gaa ctt aat gtg gct cac aat ctt atc caa tct ttc595Lys Thr Leu Lys Glu Leu Asn Val Ala His Asn Leu Ile Gln Ser Phe130 135 140aaa tta cct gag tat ttt tct aat ctg acc aat cta gag cac ttg gac643Lys Leu Pro Glu Tyr Phe Ser Asn Leu Thr Asn Leu Glu His Leu Asp145 150 155ctt tcc agc aac aag att caa agt att tat tgc aca gac ttg cgg gtt691Leu Ser Ser Asn Lys Ile Gln Ser Ile Tyr Cys Thr Asp Leu Arg Val160 165 170cta cat caa atg ccc cta ctc aat ctc tct tta gac ctg tcc ctg aay739Leu His Gln Met Pro Leu Leu Asn Leu Ser Leu Asp Leu Ser Leu Xaa175 180 185cct atg aac ttt atc caa cca ggt gca ttt aaa gaa att agg ctt cat787Pro Met Asn Phe Ile Gln Pro Gly Ala Phe Lys Glu Ile Arg Leu His190 195 200 205aag ctg act tta aga aat aat ttt gat agt tta aat gta atg aaa act835Lys Leu Thr Leu Arg Asn Asn Phe Asp Ser Leu Asn Val Met Lys Thr210 215 220tgt att caa ggt ctg gct ggt tta gaa gtc cat cgt ttg gtt ctg gga883Cys Ile Gln Gly Leu Ala Gly Leu Glu Val His Arg Leu Val Leu Gly225 230 235gaa ttt aga aat gaa gga aac ttg gaa aag ttt gac aaa tct gct cta931Glu Phe Arg Asn Glu Gly Asn Leu Glu Lys Phe Asp Lys Ser Ala Leu240 245 250gag ggc ctg tgc aat ttg acc att gaa gaa ttc cga tta gca tac tta979Glu Gly Leu Cys Asn Leu Thr Ile Glu Glu Phe Arg Leu Ala Tyr Leu255 260 265gac tac tac ctc gat gat att att gac tta ttt aat tgt ttg aca aat 1027
Asp Tyr Tyr Leu Asp Asp Ile Ile Asp Leu Phe Asn Cys Leu Thr Asn270 275 280 285gtt tct tca ttt tcc ctg gtg agt gtg act att gaa agg gta aaa gac1075Val Ser Ser Phe Ser Leu Val Ser Val Thr Ile Glu Arg Val Lys Asp290 295 300ttt tct tat aat ttc gga tgg caa cat tta gaa tta gtt aac tgt aaa1123Phe Ser Tyr Asn Phe Gly Trp Gln His Leu Glu Leu Val Asn Cys Lys305 310 315ttt gga cag ttt ccc aca ttg aaa ctc aaa tct ctc aaa agg ctt act1171Phe Gly Gln Phe Pro Thr Leu Lys Leu Lys Ser Leu Lys Arg Leu Thr320 325 330ttc act tcc aac aaa ggt ggg aat gct ttt tca gaa gtt gat cta cca1219Phe Thr Ser Asn Lys Gly Gly Asn Ala Phe Ser Glu Val Asp Leu Pro335 340 345agc ctt gag ttt cta gat ctc agt aga aat ggc ttg agt ttc aaa ggt1267Ser Leu Glu Phe Leu Asp Leu Ser Arg Asn Gly Leu Ser Phe Lys Gly350 355 360 365tgc tgt tct caa agt gat ttt ggg aca acc agc cta aag tat tta gat1315Cys Cys Ser Gln Ser Asp Phe Gly Thr Thr Ser Leu Lys Tyr Leu Asp370 375 380ctg agc ttc aat ggt gtt att acc atg agt tca aac ttc ttg ggc tta1363Leu Ser Phe Asn Gly Val Ile Thr Met Ser Ser Asn Phe Leu Gly Leu385 390 395gaa caa cta gaa cat ctg gat ttc cag cat tcc aat ttg aaa caa atg1411Glu Gln Leu Glu His Leu Asp Phe Gln His Ser Asn Leu Lys Gln Met400 405 410agt gag ttt tca gta ttc cta tca ctc aga aac ctc att tac ctt gac1459Ser Glu Phe Ser Val Phe Leu Ser Leu Arg Asn Leu Ile Tyr Leu Asp415 420 425att tct cat act cac acc aga gtt gct ttc aat ggc atc ttc aat ggc1507Ile Ser His Thr His Thr Arg Val Ala Phe Asn Gly Ile Phe Asn Gly430 435 440 445ttg tcc agt ctc gaa gtc ttg aaa atg gct ggc aat tct ttc cag gaa1555Leu Ser Ser Leu Glu Val Leu Lys Met Ala Gly Asn Ser Phe Gln Glu450 455 460aac ttc ctt cca gat atc ttc aca gag ctg aga aac ttg acc ttc ctg1603Asn Phe Leu Pro Asp Ile Phe Thr Glu Leu Arg Asn Leu Thr Phe Leu465 470 475gac ctc tct cag tgt caa ctg gag cag ttg tct cca aca gca ttt aac1651Asp Leu Ser Gln Cys Gln Leu Glu Gln Leu Ser Pro Thr Ala Phe Asn480 485 490tca ctc tcc agt ctt cag gta cta aat atg agc cac aac aac ttc ttt1699Ser Leu Ser Ser Leu Gln Val Leu Asn Met Ser His Asn Asn Phe Phe
495 500 505tca ttg gat acg ttt cct tat aag tgt ctg aac tcc ctc cag gtt ctt1747Ser Leu Asp Thr Phe Pro Tyr Lys Cys Leu Asn Ser Leu Gln Val Leu510 515 520 525gat tac agt ctc aat cac ata atg act tcc aaa aaa cag gaa cta cag1795Asp Tyr Ser Leu Asn His Ile Met Thr Ser Lys Lys Gln Glu Leu Gln530 535 540cat ttt cca agt agt cta gct ttc tta aat ctt act cag aat gac ttt1843His Phe Pro Ser Ser Leu Ala Phe Leu Asn Leu Thr Gln Asn Asp Phe545 550 555gct tgt act tgt gaa cac cag agt ttc ctg caa tgg atc aag gac cag1891Ala Cys Thr Cys Glu His Gln Ser Phe Leu Gln Trp Ile Lys Asp Gln560 565 570agg cag ctc ttg gtg gaa gtt gaa cga atg gaa tgt gca aca cct tca1939Arg Gln Leu Leu Val Glu Val Glu Arg Met Glu Cys Ala Thr Pro Ser575 580 585gat aag cag ggc atg cct gtg ctg agt ttg aat atc acc tgt cag atg1987Asp Lys Gln Gly Met Pro Val Leu Ser Leu Asn Ile Thr Cys Gln Met590 595 600 605aat aag acc atc att ggt gtg tcg gtc ctc agt gtg ctt gta gta tct2035Asn Lys Thr Ile Ile Gly Val Ser Val Leu Ser Val Leu Val Val Ser610 615 620gtt gta gca gtt ctg gtc tat aag ttc tat ttt cac ctg atg ctt ctt2083Val Val Ala Val Leu Val Tyr Lys Phe Tyr Phe His Leu Met Leu Leu625 630 635gct ggc tgc ata aag tat ggt aga ggt gaa aac atc tat gat gcc ttt2131Ala Gly Cys Ile Lys Tyr Gly Arg Gly Glu Asn Ile Tyr Asp Ala Phe640 645 650gtt atc tac tca agc cag gat gag gac tgg gta agg aat gag cta gta2179Val Ile Tyr Ser Ser Gln Asp Glu Asp Trp Val Arg Asn Glu Leu Val655 660 665aag aat tta gaa gaa ggg gtg cct cca ttt cag ctc tgc ctt cac tac2227Lys Asn Leu Glu Glu Gly Val Pro Pro Phe Gln Leu Cys Leu His Tyr670 675 680 685aga gac ttt att ccc ggt gtg gcc att gct gcc aac atc atc cat gaa2275Arg Asp Phe Ile Pro Gly Val Ala Ile Ala Ala Asn Ile Ile His Glu690 695 700ggt ttc cat aaa agc cga aag gtg att gtt gtg gtg tcc cag cac ttc2323Gly Phe His Lys Ser Arg Lys Val Ile Val Val Val Ser Gln His Phe705 710 715atc cag agc cgc tgg tgt atc ttt gaa tat gag att gct cag acc tgg2371Ile Gln Ser Arg Trp Cys Ile Phe Glu Tyr Glu Ile Ala Gln Thr Trp720 725 730
cag ttt ctg agc agt cgt gct ggt atc atc ttc att gtc ctg cag aag2419Gln Phe Leu Ser Ser Arg Ala Gly Ile Ile Phe Ile Val Leu Gln Lys735 740 745gtg gag aag acc ctg ctc agg cag cag gtg gag ctg tac cgc ctt ctc2467Val Glu Lys Thr Leu Leu Arg Gln Gln Val Glu Leu Tyr Arg Leu Leu750 755 760 765agc agg aac act tac ctg gag tgg gag gac agt gtc ctg ggg cgg cac2515Ser Arg Asn Thr Tyr Leu Glu Trp Glu Asp Ser Val Leu Gly Arg His770 775 780atc ttc tgg aga cga ctc aga aaa gcc ctg ctg gat ggt aaa tca tgg2563Ile Phe Trp Arg Arg Leu Arg Lys Ala Leu Leu Asp Gly Lys Ser Trp785 790 795aat cca gaa gga aca gtg ggt aca gga tgc aat tgg cag gaa gca aca2611Asn Pro Glu Gly Thr Val Gly Thr Gly Cys Asn Trp Gln Glu Ala Thr800 805 810tct arc tgaagaggaa aaataaaaac ctcctgaggc atttcttgcc cagctgggtc 2667Ser Ile815caacacttgt tcagttaata agtattaaat gctgccacat gtcaggcctt atgctaaggg 2727tgagtaattc catggtgcac tagatatgca gggctgctaa tctcaaggag cttccagtgc 2787agagggaata aatgctagac taaaatacag agtcttccag gtgggcattt caaccaactc 2847agtcaaggaa cccatgacaa agaaagtcat ttcaactctt acctcatcaa gttgaataaa 2907gacagagaaa acagaaagag acattgttct tttcctgagt cttttgaatg gaaattgtat 2967tatgttatag ccatcataaa accattttgg tagttttgac tgaactgggt gttcactttt 3027tcctttttga ttgaatacaa tttaaattct acttgatgac tgcagtcgtc aaggggctcc 3087tgatgcaaga tgccccttcc attttaagtc tgtctcctta cagakgttaa agtctantgg 3147ctaattccta aggaaacctg attaacacat gctcacaacc atcctggtca ttctcganca 3207tgttctattt tttaactaat cacccctgat atatttttat ttttatatat ccagttttca 3267tttttttacg tcttgcctat aagctaatat cataaataag gttgtttaag acgtgcttca 3327aatatccata ttaaccacta tttttcaagg aagtatggaa aagtacactc tgtcactttg 3387tcactcgatg tcattccaaa gttattgcct actaagtaat gactgtcatg aaagcagcat 3447tgaaataatt tgtttaaagg gggcactctt ttaaacggga agaaaatttc cgcttcctgg 3507tcttatcatg gacaatttgg gctakaggca kgaaggaagt gggatkacct caggangtca 3567ccttttcttg attccagaaa catatgggct gataaacccg gggtgacctc atgaaatgag 3627
ttgcagcaga wgtttatttt tttcagaaca agtgatgttt gatggacctm tgaatctmtt 3687tagggagaca cagatggctg ggatccctcc cctgtaccct tctcactgmc aggagaacta 3747cgtgtgaagg tattcaaggc agggagtata cattgctgtt tcctgttggg caatgctcct 3807tgaccacatt ttgggaagag tggatgttat cattgagaaa acaatgtgtc tggaattaat 3867ggggttctta taaagaaggt tcccagaaaa gaatgttcat tccagcttct tcaggaaaca 3927ggaacattca aggaaaagga caatcaggat gtcatcaggg aaatgaaaat aaaaaccaca 3987atgagatatc accttatacc aggtagatgg ctactataaa aaaatgaagt gtcatcaagg 4047atatagagaa attggaaccc ttcttcactg ctggagggaa tggaaaatgg tgtagccgtt 4107atgaaaaaca gtacggaggt ttctcaaaaa ttaaaaatag aactgctata tgatccagca 4167atctcacttc tgtatatata cccaaaataa ttgaaatcag aatttcaaga aaatatttac 4227actcccatgt tcattgtggc actcttcaca atcactgttt ccaaagttat ggaaacaacc 4287caaatttcca ttggaaaata aatggacaaa ggaaatgtgc atataacgta caatggggat 4347attattcagc ctaaaaaaag gggggatcct gttatttatg acaacatgaa taaacccgga 4407ggccattatg ctatgtaaaa tgagcaagta acagaaagac aaatactgcc tgatttcatt 4467tatatgaggt tctaaaatag tcaaactcat agaagcagag aatagaacag tggttcctag 4527ggaaaaggag gaagggagaa atgaggaaat agggagttgt ctaattggta taaaattata 4587gtatgcaaga tgaattagct ctaaagatca gctgtatagc agagttcgta taatgaacaa 4647tactgtatta tgcacttaac attttgttaa gagggtacct ctcatgttaa gtgttcttac 4707catatacata tacacaagga agcttttgga ggtgatggat atatttatta ccttgattgt 4767ggtgatggtt tgacaggtat gtgactatgt ctaaactcat caaattgtat acattaaata 4827tatgcagttt tataatatca aaaaaaaaaa aaaaaaaa 4865<210>26<211>837<212>PRT<213>未知<400>26Met Ser Ala Ser Arg Leu Ala Gly Thr Leu Ile Pro Ala Met Ala Phe-20 -15 -10Leu Ser Cys Val Arg Pro Glu Ser Trp Glu Pro Cys Val Glu Val Pro-5 -1 1 5 10Asn Ile Thr Tyr Gln Cys Met Glu Leu Asn Phe Tyr Lys Ile Pro Asp15 20 25
Asn Leu Pro Phe Ser Thr Lys Asn Leu Asp Leu Ser Phe Asn Pro Leu30 35 40Arg His Leu Gly Ser Tyr Ser Phe Phe Ser Phe Pro Glu Leu Gln Val45 50 55Leu Asp Leu Ser Arg Cys Glu Ile Gln Thr Ile Glu Asp Gly Ala Tyr60 65 70Gln Ser Leu Ser His Leu Ser Thr Leu Ile Leu Thr Gly Asn Pro Ile75 80 85 90Gln Ser Leu Ala Leu Gly Ala Phe Ser Gly Leu Ser Ser Leu Gln Lys95 100 105Leu Val Ala Val Glu Thr Asn Leu Ala Ser Leu Glu Asn Phe Pro Ile110 115 120Gly His Leu Lys Thr Leu Lys Glu Leu Asn Val Ala His Asn Leu Ile125 130 135Gln Ser Phe Lys Leu Pro Glu Tyr Phe Ser Asn Leu Thr Asn Leu Glu140 145 150His Leu Asp Leu Ser Ser Asn Lys Ile Gln Ser Ile Tyr Cys Thr Asp155 160 165 170Leu Arg Val Leu His Gln Met Pro Leu Leu Asn Leu Ser Leu Asp Leu175 180 185Ser Leu Xaa Pro Met Asn Phe Ile Gln Pro Gly Ala Phe Lys Glu Ile190 195 200Arg Leu His Lys Leu Thr Leu Arg Asn Asn Phe Asp Ser Leu Asn Val205 210 215Met Lys Thr Cys Ile Gln Gly Leu Ala Gly Leu Glu Val His Arg Leu220 225 230Val Leu Gly Glu Phe Arg Asn Glu Gly Asn Leu Glu Lys Phe Asp Lys235 240 245 250Ser Ala Leu Glu Gly Leu Cys Asn Leu Thr Ile Glu Glu Phe Arg Leu255 260 265Ala Tyr Leu Asp Tyr Tyr Leu Asp Asp Ile Ile Asp Leu Phe Asn Cys270 275 280Leu Thr Asn Val Ser Ser Phe Ser Leu Val Ser Val Thr Ile Glu Arg285 290 295Val Lys Asp Phe Ser Tyr Asn Phe Gly Trp Gln His Leu Glu Leu Val300 305 310Asn Cys Lys Phe Gly Gln Phe Pro Thr Leu Lys Leu Lys Ser Leu Lys315 320 325 330
Arg Leu Thr Phe Thr Ser Asn Lys Gly Gly Asn Ala Phe Ser Glu Val335 340 345Asp Leu Pro Ser Leu Glu Phe Leu Asp Leu Ser Arg Asn Gly Leu Ser350 355 360Phe Lys Gly Cys Cys Ser Gln Ser Asp Phe Gly Thr Thr Ser Leu Lys365 370 375Tyr Leu Asp Leu Ser Phe Asn Gly Val Ile Thr Met Ser Ser Asn Phe380 385 390Leu Gly Leu Glu Gln Leu Glu His Leu Asp Phe Gln His Ser Asn Leu395 400 405 410Lys Gln Met Ser Glu Phe Ser Val Phe Leu Ser Leu Arg Asn Leu Ile415 420 425Tyr Leu Asp Ile Ser His Thr His Thr Arg Val Ala Phe Asn Gly Ile430 435 440Phe Asn Gly Leu Ser Ser Leu Glu Val Leu Lys Met Ala Gly Asn Ser445 450 455Phe Gln Glu Asn Phe Leu Pro Asp Ile Phe Thr Glu Leu Arg Asn Leu460 465 470Thr Phe Leu Asp Leu Ser Gln Cys Gln Leu Glu Gln Leu Ser Pro Thr475 480 485 490Ala Phe Asn Ser Leu Ser Ser Leu Gln Val Leu Asn Met Ser His Asn495 500 505Asn Phe Phe Ser Leu Asp Thr Phe Pro Tyr Lys Cys Leu Asn Ser Leu510 515 520Gln Val Leu Asp Tyr Ser Leu Asn His Ile Met Thr Ser Lys Lys Gln525 530 535Glu Leu Gln His Phe Pro Ser Ser Leu Ala Phe Leu Asn Leu Thr Gln540 545 550Asn Asp Phe Ala Cys Thr Cys Glu His Gln Ser Phe Leu Gln Trp Ile555 560 565 570Lys Asp Gln Arg Gln Leu Leu Val Glu Val Glu Arg Met Glu Cys Ala575 580 585Thr Pro Ser Asp Lys Gln Gly Met Pro Val Leu Ser Leu Asn Ile Thr590 595 600Cys Gln Met Asn Lys Thr Ile Ile Gly Val Ser Val Leu Ser Val Leu605 610 615Val Val Ser Val Val Ala Val Leu Val Tyr Lys Phe Tyr Phe His Leu620 625 630
Met Leu Leu Ala Gly Cys Ile Lys Tyr Gly Arg Gly Glu Asn Ile Tyr635 640 645 650Asp Ala Phe Val Ile Tyr Ser Ser Gln Asp Glu Asp Trp Val Arg Asn655 660 665Glu Leu Val Lys Asn Leu Glu Glu Gly Val Pro Pro Phe Gln Leu Cys670 675 680Leu His Tyr Arg Asp Phe Ile Pro Gly Val Ala Ile Ala Ala Asn Ile685 690 695Ile His Glu Gly Phe His Lys Ser Arg Lys Val Ile Val Val Val Ser700 705 710Gln His Phe Ile Gln Ser Arg Trp Cys Ile Phe Glu Tyr Glu Ile Ala715 720 725 730Gln Thr Trp Gln Phe Leu Ser Ser Arg Ala Gly Ile Ile Phe Ile Val735 740 745Leu Gln Lys Val Glu Lys Thr Leu Leu Arg Gln Gln Val Glu Leu Tyr750 755 760Arg Leu Leu Ser Arg Asn Thr Tyr Leu Glu Trp Glu Asp Ser Val Leu765 770 775Gly Arg His Ile Phe Trp Arg Arg Leu Arg Lys Ala Leu Leu Asp Gly780 785 790Lys Ser Trp Asn Pro Glu Gly Thr Val Gly Thr Gly Cys Asn Trp Gln795 800 805 810Glu Ala Thr Ser Ile815<210>27<211>300<212>DNA<213>未知<220>
<223>未知生物的说明啮齿类动物；推测为小鼠(Mus musculus)<220>
<221>CDS<222>(1)..(300)<220>
<221>misc_特征<222>(62)..(100)<223>Xaa翻译取决于遗传密码
<400>27tcc tat tct atg gaa aaa gat gct ttc cta ttt atg aga aat ttg aag 48Ser Tyr Ser Met Glu Lys Asp Ala Phe Leu Phe Met Arg Asn Leu Lys1 5 10 15gtt ctc tca cta aaa gat aac aat gtc aca gct gtc ccc acc act ttg 96Val Leu Ser Leu Lys Asp Asn Asn Val Thr Ala Val Pro Thr Thr Leu20 25 30cca cct aat tta cta gag ctc tat ctt tat aac aat atc att aag aaa144Pro Pro Asn Leu Leu Glu Leu Tyr Leu Tyr Asn Asn Ile Ile Lys Lys35 40 45atc caa gaa aat gat ttc aat aac ctc aat gag ttg caa gtn ctt gac192Ile Gln Glu Asn Asp Phe Asn Asn Leu Asn Glu Leu Gln Xaa Leu Asp50 55 60cta ngt gga aat tgc cct cga tgt nat aat gtc cca tat ccg tgt aca240Leu Xaa Gly Asn Cys Pro Arg Cys Xaa Asn Val Pro Tyr Pro Cys Thr65 70 75 80ccg tgt gaa aat aat tcc ccc tta cag atc cat gan aat gct ttc aat288Pro Cys Glu Asn Asn Ser Pro Leu Gln Ile His Xaa Asn Ala Phe Asn85 90 95tca tcg aca gan300Ser Ser Thr Xaa100<210>28<211>100<212>PRT<213>未知<400>28Ser Tyr Ser Met Glu Lys Asp Ala Phe Leu Phe Met Arg Asn Leu Lys1 5 10 15Val Leu Ser Leu Lys Asp Asn Asn Val Thr Ala Val Pro Thr Thr Leu20 25 30Pro Pro Asn Leu Leu Glu Leu Tyr Leu Tyr Asn Asn Ile Ile Lys Lys35 40 45Ile Gln Glu Asn Asp Phe Asn Asn Leu Asn Glu Leu Gln Xaa Leu Asp50 55 60Leu Xaa Gly Asn Cys Pro Arg Cys Xaa Asn Val Pro Tyr Pro Cys Thr65 70 75 80Pro Cys Glu Asn Asn Ser Pro Leu Gln Ile His Xaa Asn Ala Phe Asn85 90 95Ser Ser Thr Xaa100
<210>29<211>1756<212>DNA<213>未知<220>
<223>未知生物的说明啮齿类动物；推测为小鼠(Mus musculus)<220>
<221>CDS<222>(1)..(1182)<400>29tct cca gaa att ccc tgg aat tcc ttg cct cct gag gtt ttt gag ggt 48Ser Pro Glu Ile Pro Trp Asn Ser Leu Pro Pro Glu Val Phe Glu Gly1 5 10 15atg ccg cca aat cta aag aat ctc tcc ttg gcc aaa aat ggg ctc aaa 96Met Pro Pro Asn Leu Lys Asn Leu Ser Leu Ala Lys Asn Gly Leu Lys20 25 30tct ttc ttt tgg gac aga ctc cag tta ctg aag cat ttg gaa att ttg144Ser Phe Phe Trp Asp Arg Leu Gln Leu Leu Lys His Leu Glu Ile Leu35 40 45gac ctc agc cat aac cag ctg aca aaa gta cct gag aga ttg gcc aac192Asp Leu Ser His Asn Gln Leu Thr Lys Val Pro Glu Arg Leu Ala Asn50 55 60tgt tcc aaa agt ctc aca aca ctg att ctt aag cat aat caa atc agg240Cys Ser Lys Ser Leu Thr Thr Leu Ile Leu Lys His Asn Gln Ile Arg65 70 75 80caa ttg aca aaa tat ttt cta gaa gat gct ttg caa ttg cgc tat cta288Gln Leu Thr Lys Tyr Phe Leu Glu Asp Ala Leu Gln Leu Arg Tyr Leu85 90 95gac atc agt tca aat aaa atc cag gtc att cag aag act agc ttc cca336Asp Ile Ser Ser Asn Lys Ile Gln Val Ile Gln Lys Thr Ser Phe Pro100 105 110gaa aat gtc ctc aac aat ctg gag atg ttg gtt tta cat cac aat cgc384Glu Asn Val Leu Asn Asn Leu Glu Met Leu Val Leu His His Asn Arg115 120 125ttt ctt tgc aac tgt gat gct gtg tgg ttt gtc tgg tgg gtt aac cat432Phe Leu Cys Asn Cys Asp Ala Val Trp Phe Val Trp Trp Val Asn His130 135 140aca gat gtt act att cca tac ctg gcc act gat gtg act tgt gta ggt480Thr Asp Val Thr Ile Pro Tyr Leu Ala Thr Asp Val Thr Cys Val Gly145 150 155 160cca gga gca cac aaa ggt caa agt gtc ata tcc ctt gat ctg tat acg528
Pro Gly Ala His Lys Gly Gln Ser Val Ile Ser Leu Asp Leu Tyr Thr165 170 175tgt gag tta gat ctc aca aac ctg att ctg ttc tca gtt tcc ata tca576Cys Glu Leu Asp Leu Thr Asn Leu Ile Leu Phe Ser Val Ser Ile Ser180 185 190tca gtc ctc ttt ctt atg gta gtt atg aca aca agt cac ctc ttt ttc624Ser Val Leu Phe Leu Met Val Val Met Thr Thr Ser His Leu Phe Phe195 200 205tgg gat atg tgg tac att tat tat ttt tgg aaa gca aag ata aag ggg672Trp Asp Met Trp Tyr Ile Tyr Tyr Phe Trp Lys Ala Lys Ile Lys Gly210 215 220tat cca gca tct gca atc cca tgg agt cct tgt tat gat gct ttt att720Tyr Pro Ala Ser Ala Ile Pro Trp Ser Pro Cys Tyr Asp Ala Phe Ile225 230 235 240gtg tat gac act aaa aac tca gct gtg aca gaa tgg gtt ttg cag gag768Val Tyr Asp Thr Lys Asn Ser Ala Val Thr Glu Trp Val Leu Gln Glu245 250 255ctg gtg gca aaa ttg gaa gat cca aga gaa aaa cac ttc aat ttg tgt816Leu Val Ala Lys Leu Glu Asp Pro Arg Glu Lys His Phc Asn Leu Cys260 265 270cta gaa gaa aga gac tgg cta cca gga cag cca gtt cta gaa aac ctt864Leu Glu Glu Arg Asp Trp Leu Pro Gly Gln Pro Val Leu Glu Asn Leu275 280 285tcc cag agc ata cag ctc agc aaa aag aca gtg ttt gtg atg aca cag912Ser Gln Ser Ile Gln Leu Ser Lys Lys Thr Val Phe Val Met Thr Gln290 295 300aaa tat gct aag act gag agt ttt aag atg gca ttt tat ttg tct cat960Lys Tyr Ala Lys Thr Glu Ser Phe Lys Met Ala Phe Tyr Leu Ser His305 310 315 320cag agg ctc ctg gat gaa aaa gtg gat gtg att atc ttg ata ttc ttg 1008Gln Arg Leu Leu Asp Glu Lys Val Asp Val Ile Ile Leu Ile Phe Leu325 330 335gaa aga cct ctt cag aag tct aag ttt ctt cag ctc agg aag aga ctc 1056Glu Arg Pro Leu Gln Lys Ser Lys Phe Leu Gln Leu Arg Lys Arg Leu340 345 350tgc agg agc tct gtc ctt gag tgg cct gca aat cca cag gct cac cca 1104Cys Arg Ser Ser Val Leu Glu Trp Pro Ala Asn Pro Gln Ala His Pro355 360 365tac ttc tgg cag tgc ctg aaa aat gcc ctg acc aca gac aat cat gtg 1152Tyr Phe Trp Gln Cys Leu Lys Asn Ala Leu Thr Thr Asp Asn His Val370 375 380gct tat agt caa atg ttc aag gaa aca gtc tagctctctg aagaatgtca 1202Ala Tyr Ser Gln Met Phe Lys Glu Thr Val
385390ccacctagga catgccttgg tacctgaagt tttcataaag gtttccataa atgaaggtct 1262gaatttttcc taacagttgt catggctcag attggtggga aatcatcaat atatggctaa 1322gaaattaaga aggggagact gatagaagat aatttctttc ttcatgtgcc atgctcagtt 1382aaatatttcc cctagctcaa atctgaaaaa ctgtgcctag gagacaacac aaggctttga 1442tttatctgca tacaattgat aagagccaca catctgccct gaagaagtac tagtagtttt 1502agtagtaggg taaaaattac acaagctttc tctctctctg atactgaact gtaccagagt 1562tcaatgaaat aaaagcccag agaacttctc agtaaatggt ttcattatca tgtagtatcc 1622accatgcaat atgccacaaa rccgctactg gtacaggaca gntggtagct gcttcaakgc 1682ctcttatcat tttcttgggg cccatggagg ggttctytgg gaaadaggga agkttttttt 1742tggccatcca tgaa 1756<210>30<211>394<212>PRT<213>未知<400>30Ser Pro Glu Ile Pro Trp Asn Ser Leu Pro Pro Glu Val Phe Glu Gly1 5 10 15Met Pro Pro Asn Leu Lys Asn Leu Ser Leu Ala Lys Asn Gly Leu Lys20 25 30Ser Phe Phe Trp Asp Arg Leu Gln Leu Leu Lys His Leu Glu Ile Leu35 40 45Asp Leu Ser His Asn Gln Leu Thr Lys Val Pro Glu Arg Leu Ala Asn50 55 60Cys Ser Lys Ser Leu Thr Thr Leu Ile Leu Lys His Asn Gln Ile Arg65 70 75 80Gln Leu Thr Lys Tyr Phe Leu Glu Asp Ala Leu Gln Leu Arg Tyr Leu85 90 95Asp Ile Ser Ser Asn Lys Ile Gln Val Ile Gln Lys Thr Ser Phe Pro100 105 110Glu Asn Val Leu Asn Asn Leu Glu Met Leu Val Leu His His Asn Arg115 120 125Phe Leu Cys Asn Cys Asp Ala Val Trp Phe Val Trp Trp Val Asn His130 135 140Thr Asp Val Thr Ile Pro Tyr Leu Ala Thr Asp Val Thr Cys Val Gly
145 150 155 160Pro Gly Ala His Lys Gly Gln Ser Val Ile Ser Leu Asp Leu Tyr Thr165 170 175Cys Glu Leu Asp Leu Thr Asn Leu Ile Leu Phe Ser Val Ser Ile Ser180 185 190Ser Val Leu Phe Leu Met Val Val Met Thr Thr Ser His Leu Phe Phe195 200 205Trp Asp Met Trp Tyr Ile Tyr Tyr Phe Trp Lys Ala Lys Ile Lys Gly210 215 220Tyr Pro Ala Ser Ala Ile Pro Trp Ser Pro Cys Tyr Asp Ala Phe Ile225 230 235 240Val Tyr Asp Thr Lys Asn Ser Ala Val Thr Glu Trp Val Leu Gln Glu245 250 255Leu Val Ala Lys Leu Glu Asp Pro Arg Glu Lys His Phe Asn Leu Cys260 265 270Leu Glu Glu Arg Asp Trp Leu Pro Gly Gln Pro Val Leu Glu Asn Leu275 280 285Ser Gln Ser Ile Gln Leu Ser Lys Lys Thr Val Phe Val Met Thr Gln290 295 300Lys Tyr Ala Lys Thr Glu Ser Phe Lys Met Ala Phe Tyr Leu Ser His305 310 315 320Gln Arg Leu Leu Asp Glu Lys Val Asp Val Ile Ile Leu Ile Phe Leu325 330 335Glu Arg Pro Leu Gln Lys Ser Lys Phe Leu Gln Leu Arg Lys Arg Leu340 345 350Cys Arg Ser Ser Val Leu Glu Trp Pro Ala Asn Pro Gln Ala His Pro355 360 365Tyr Phe Trp Gln Cys Leu Lys Asn Ala Leu Thr Thr Asp Asn His Val370 375 380Ala Tyr Ser Gln Met Phe Lys Glu Thr Val385 390<210>31<211>999<212>DNA<213>未知<220>
<223>未知生物的说明灵长类动物；推测为人(Homo sapiens)
<220>
<221>CDS<222>(2)..(847)<220>
<221>misc_特征<222>(1)..(282)<223>Xaa翻译取决于遗传密码<400>31c tcn gat gcc aag att cgg cac nag gca tat tca gag gtc atg atg gtt 49Xaa Asp Ala Lys Ile Arg His Xaa Ala Tyr Ser Glu Val Met Met Val1 5 10 15gga tgg tca gat tca tac acc tgt gaa tac cct tta aac cta agg gga 97Gly Trp Ser Asp Ser Tyr Thr Cys Glu Tyr Pro Leu Asn Leu Arg Gly20 25 30act agg tta aaa gac gtt cat ctc cac gaa tta tct tgc aac aca gct145Thr Arg Leu Lys Asp Val His Leu His Glu Leu Ser Cys Asn Thr Ala35 40 45ctg ttg att gtc acc att gtg gtt att atg cta gtt ctg ggg ttg gct193Leu Leu Ile Val Thr Ile Val Val Ile Met Leu Val Leu Gly Leu Ala50 55 60gtg gcc ttc tgc tgt ctc cac ttt gat ctg ccc tgg tat ctc agg atg241Val Ala Phe Cys Cys Leu His Phe Asp Leu Pro Trp Tyr Leu Arg Met65 70 75 80cta ggt caa tgc aca caa aca tgg cac agg gtt agg aaa aca acc caa289Leu Gly Gln Cys Thr Gln Thr Trp His Arg Val Arg Lys Thr Thr Gln85 90 95gaa caa ctc aag aga aat gtc cga ttc cac gca ttt att tca tac agt337Glu Gln Leu Lys Arg Asn Val Arg Phe His Ala Phe Ile Ser Tyr Ser100 105 110gaa cat gat tct ctg tgg gtg aag aat gaa ttg atc ccc aat cta gag385Glu His Asp Ser Leu Trp Val Lys Asn Glu Leu Ile Pro Asn Leu Glu115 120 125aag gaa gat ggt tct atc ttg att tgc ctt tat gaa agc tac ttt gac433Lys Glu Asp Gly Ser Ile Leu Ile Cys Leu Tyr Glu Ser Tyr Phe Asp130 135 140cct ggc aaa agc att agt gaa aat att gta agc ttc att gag aaa agc481Pro Gly Lys Ser Ile Ser Glu Asn Ile Val Ser Phe Ile Glu Lys Ser145 150 155 160tat aag tcc atc ttt gtt ttg tct ccc aac ttt gtc cag aat gag tgg529Tyr Lys Ser Ile Phe Val Leu Ser Pro Asn Phe Val Gln Asn Glu Trp165 170 175tgc cat tat gaa ttc tac ttt gcc cac cac aat ctc ttc cat gaa aat577
Cys His Tyr Glu Phe Tyr Phe Ala His His Asn Leu Phe His Glu Asn180 185 190tct gat cac ata att ctt atc tta ctg gaa ccc att cca ttc tat tgc625Ser Asp His Ile Ile Leu Ile Leu Leu Glu Pro Ile Pro Phe Tyr Cys195 200 205att ccc acc agg tat cat aaa ctg raa gct ctc ctg gaa aaa aaa gca673Ile Pro Thr Arg Tyr His Lys Leu Xaa Ala Leu Leu Glu Lys Lys Ala210 215 220tac ttg gaa tgg ccc aag gat agg cgt aaa tgt ggg ctt tty tgg gca721Tyr Leu Glu Trp Pro Lys Asp Arg Arg Lys Cys Gly Leu Xaa Trp Ala225 230 235 240aac ctt cga gct gct gtt aat gtt aat gta tta gcc acc aga gaa atg769Asn Leu Arg Ala Ala Val Asn Val Asn Val Leu A la Thr Arg Glu Met245 250 255tat gaa ctg cag aca ttc aca gag tta aat gaa gag tct cga ggt tct817Tyr Glu Leu Gln Thr Phe Thr Glu Leu Asn Glu Glu Ser Arg Gly Ser260 265 270aca atc tyt ctg atg aga aca gac tgt yta taaaatccca cagtccttgg 867Thr Ile Xaa Leu Met Arg Thr Asp Cys Xaa275 280gaagttgggg accacataca ctgttgggat gtacattgat acaaccttta tgatggcaat 927ttgacaatat ttattaaaat aaaaaatggt tattcccttc aaaaaaaaaa aaaaaaaaaa 987aaaaaaaaaa aa 999<210>32<211>282<212>PRT<213>未知<400>32Xaa Asp Ala Lys Ile Arg His Xaa Ala Tyr Ser Glu Val Met Met Val1 5 10 15Gly Trp Ser Asp Ser Tyr Thr Cys Glu Tyr Pro Leu Asn Leu Arg Gly20 25 30Thr Arg Leu Lys Asp Val His Leu His Glu Leu Ser Cys Asn Thr Ala35 40 45Leu Leu Ile Val Thr Ile Val Val Ile Met Leu Val Leu Gly Leu Ala50 55 60Val Ala Phe Cys Cys Leu His Phe Asp Leu Pro Trp Tyr Leu Arg Met65 70 75 80Leu Gly Gln Cys Thr Gln Thr Trp His Arg Val Arg Lys Thr Thr Gln85 90 95
Glu Gln Leu Lys Arg Asn Val Arg Phe His Ala Phe Ile Ser Tyr Ser100 105 110Glu His Asp Ser Leu Trp Val Lys Asn Glu Leu Ile Pro Asn Leu Glu115 120 125Lys Glu Asp Gly Ser Ile Leu Ile Cys Leu Tyr Glu Ser Tyr Phe Asp130 135 140Pro Gly Lys Ser Ile Ser Glu Asn Ile Val Ser Phe Ile Glu Lys Ser145 150 155 160Tyr Lys Ser Ile Phe Val Leu Ser Pro Asn Phe Val Gln Asn Glu Trp165 170 175Cys His Tyr Glu Phe Tyr Phe Ala His His Asn Leu Phe His Glu Asn180 185 190Ser Asp His Ile Ile Leu Ile Leu Leu Glu Pro Ile Pro Phe Tyr Cys195 200 205Ile Pro Thr Arg Tyr His Lys Leu Xaa Ala Leu Leu Glu Lys Lys Ala210 215 220Tyr Leu Glu Trp Pro Lys Asp Arg Arg Lys Cys Gly Leu Xaa Trp Ala225 230 235 240Asn Leu Arg Ala Ala Val Asn Val Asn Val Leu Ala Thr Arg Glu Met245 250 255Tyr Gtu Leu Gln Thr Phe Thr Glu Leu Asn Glu Glu Ser Arg Gly Ser260 265 270Thr Ile Xaa Leu Met Arg Thr Asp Cys Xaa275 280<210>33<211>1173<212>DNA<213>未知<220>
<223>未知生物的说明灵长类动物；推测为人(Homo sapiens)<220>
<22l>CDS<222>(1)..(1008)<220>
<22l>misc_特征<222>(285)<223>Xaa翻译取决于遗传密码
<400>33ctg cct gct ggc acc cgg ctc cgg agg ctg gat gtc agc tgc aac agc48Leu Pro Ala Gly Thr Arg Leu Arg Arg Leu Asp Val Ser Cys Asn Ser1 5 10 15atc agc ttc gtg gcc ccc ggc ttc ttt tcc aag gcc aag gag ctg cga96Ile Ser Phe Val Ala Pro Gly Phe Phe Ser Lys Ala Lys Glu Leu Arg20 25 30gag ctc aac ctt agc gcc aac gcc ctc aag aca gtg gac cac tcc tgg144Glu Leu Asn Leu Ser Ala Asn Ala Leu Lys Thr Val Asp His Ser Trp35 40 45ttt ggg ccc ctg gcg agt gcc ctg caa ata cta gat gta agc gcc aac192Phe Gly Pro Leu Ala Ser Ala Leu Gln Ile Leu Asp Val Ser Ala Asn50 55 60cct ctg cac tgc gcc tgt ggg gcg gcc ttt atg gac ttc ctg ctg gag240Pro Leu His Cys Ala Cys Gly Ala Ala Phe Met Asp Phe Leu Leu Glu65 70 75 80gtg cag gct gcc gtg ccc ggt ctg ccc agc cgg gtg aag tgt ggc agt288Val Gln Ala Ala Val Pro Gly Leu Pro Ser Arg Val Lys Cys Gly Ser85 90 95ccg ggc cag ctc cag ggc ctc agc atc ttt gca cag gac ctg cgc ctc336Pro Gly Gln Leu Gln Gly Leu Ser Ile Phe Ala Gln Asp Leu Arg Leu100 105 110tgc ctg gat gag gcc ctc tcc tgg gac tgt ttc gcc ctc tcg ctg ctg384Cys Leu Asp Glu Ala Leu Ser Trp Asp Cys Phe Ala Leu Ser Leu Leu115 120 125gct gtg gct ctg ggc ctg ggt gtg ccc atg ctg cat cac ctc tgt ggc432Ala Val Ala Leu Gly Leu Gly Val Pro Met Leu His His Leu Cys Gly130 135 140tgg gac ctc tgg tac tgc ttc cac ctg tgc ctg gcc tgg ctt ccc tgg480Trp Asp Leu Trp Tyr Cys Phe His Leu Cys Leu Ala Trp Leu Pro Trp145 150 155 160cgg ggg cgg caa agt ggg cga gat gag gat gcc ctg ccc tac gat gcc528Arg Gly Arg Gln Ser Gly Arg Asp Glu Asp Ala Leu Pro Tyr Asp Ala165 170 175ttc gtg gtc ttc gac aaa acg cag agc gca gtg gca gac tgg gtg tac576Phe Val Val Phe Asp Lys Thr Gln Ser Ala Val Ala Asp Trp Val Tyr180 185 190aac gag ctt cgg ggg cag ctg gag gag tgc cgt ggg cgc tgg gca ctc624Asn Glu Leu Arg Gly Gln Leu Glu Glu Cys Arg Gly Arg Trp Ala Leu195 200 205cgc ctg tgc ctg gag gaa cgc gac tgg ctg cct ggc aaa acc ctc ttt672Arg Leu Cys Leu Glu Glu Arg Asp Trp Leu Pro Gly Lys Thr Leu Phe210 215 220
gag aac ctg tgg gcc tcg gtc tat ggc agc cgc aag acg ctg ttt gtg720Glu Asn Leu Trp Ala Ser Val Tyr Gly Ser Arg Lys Thr Leu Phe Val225 230 235 240ctg gcc cac acg gac cgg gtc agt ggt ctc ttg cgc gcc agc ttc ctg768Leu Ala His Thr Asp Arg Val Ser Gly Leu Leu Arg Ala Ser Phe Leu245 250 255ctg gcc cag cag cgc ctg ctg gag gac cgc aag gac gtc gtg gtg ctg816Leu Ala Gln Gln Arg Leu Leu Glu Asp Arg Lys Asp Val Val Val Leu260 265 270gtg atc ctg agc cct gac ggc cgc cgc tcc cgc tac gkg cgg ctg cgc864Val Ile Leu Ser Pro Asp Gly Arg Arg Ser Arg Tyr Xaa Arg Leu Arg275 280 285cag cgc ctc tgc cgc cag agt gtc ctc ctc tgg ccc cac cag ccc agt912Gln Arg Leu Cys Arg Gln Ser Val Leu Leu Trp Pro His Gln Pro Ser290 295 300ggt cag cgc agc ttc tgg gcc cag ctg ggc atg gcc ctg acc agg gac960Gly Gln Arg Ser Phe Trp Ala Gln Leu Gly Met Ala Leu Thr Arg Asp305 310 315 320aac cac cac ttc tat aac cgg aac ttc tgc cag gga ccc acg gcc gaa 1008Asn His His Phe Tyr Asn Arg Asn Phe Cys Gln Gly Pro Thr Ala Glu325 330 335tagccgtgag ccggaatcct gcacggtgcc acctccacac tcacctcacc tctgcctgcc 1068tggtctgacc ctcccctgct cgcctccctc accccacacc tgacacagag caggcactca 1128ataaatgcta ccgaaggcta aaaaaaaaaa aaaaaaaaaa aanna 1173<210>34<211>336<212>PRT<213>未知<400>34Leu Pro Ala Gly Thr Arg Leu Arg Arg Leu Asp Val Ser Cys Asn Ser1 5 10 15Ile Ser Phe Val Ala Pro Gly Phe Phe Ser Lys Ala Lys Glu Leu Arg20 25 30Glu Leu Asn Leu Ser Ala Asn Ala Leu Lys Thr Val Asp His Ser Trp35 40 45Phe Gly Pro Leu Ala Ser Ala Leu Gln Ile Leu Asp Val Ser Ala Asn50 55 60Pro Leu His Cys Ala Cys Gly Ala Ala Phe Met Asp Phe Leu Leu Glu65 70 75 80Val Gln Ala Ala Val Pro Gly Leu Pro Ser Arg Val Lys Cys Gly Ser
85 90 95Pro Gly Gln Leu Gln Gly Leu Ser Ile Phe Ala Gln Asp Leu Arg Leu100 105 110Cys Leu Asp Glu Ala Leu Ser Trp Asp Cys Phe Ala Leu Ser Leu Leu115 120 125Ala Val Ala Leu Gly Leu Gly Val Pro Met Leu His His Leu Cys Gly130 135 140Trp Asp Leu Trp Tyr Cys Phe His Leu Cys Leu Ala Trp Leu Pro Trp145 150 155 160Arg Gly Arg Gln Ser Gly Arg Asp Glu Asp Ala Leu Pro Tyr Asp Ala165 170 175Phe Val Val Phe Asp Lys Thr Gln Ser Ala Val Ala Asp Trp Val Tyr180 185 190Asn Glu Leu Arg Gly Gln Leu Glu Glu Cys Arg Gly Arg Trp Ala Leu195 200 205Arg Leu Cys Leu Glu Glu Arg Asp Trp Leu Pro Gly Lys Thr Leu Phe210 215 220Glu Asn Leu Trp Ala Ser Val Tyr Gly Ser Arg Lys Thr Leu Phe Val225 230 235 240Leu Ala His Thr Asp Arg Val Ser Gly Leu Leu Arg Ala Ser Phe Leu245 250 255Leu Ala Gln Gln Arg Leu Leu Glu Asp Arg Lys Asp Val Val Val Leu260 265 270Val Ile Leu Ser Pro Asp Gly Arg Arg Ser Arg Tyr Xaa Arg Leu Arg275 280 285Gln Arg Leu Cys Arg Gln Ser Val Leu Leu Trp Pro His Gln Pro Ser290 295 300Gly Gln Arg Ser Phe Trp Ala Gln Leu Gly Met Ala Leu Thr Arg Asp305 310 315 320Asn His His Phe Tyr Asn Arg Asn Phe Cys Gln Gly Pro Thr Ala Glu325 330 335<210>35<211>497<212>DNA<213>未知<220>
<223>未知生物的说明啮齿类动物；推测为小鼠(Mus musculus)
<400>35tggcccacac ggaccgcgtc agtggcctcc tgcgcaccag cttcctgctg gctcagcagc 60gcctgttgga agaccgcaag gacgtggtgg tgttggtgat cctgcgtccg gatgccccac 120cgtcccgcta tgtgcgactg cgccagcgtc tctgccgcca gagtgtgctc ttctggcccc 180agcgacccaa cgggcagggg ggcttctggg cccagctgag tacagccctg actagggaca 240accgccactt ctataaccag aacttctgcc ggggacctac agcagaatag ctcagagcaa 300cagctggaaa cagctgcatc ttcatgtctg gttcccgagt tgctctgcct gccttgctct 360gtcttactac accgctattt ggcaagtgcg caatatatgc taccaagcca ccaggcccac 420ggagcaaagg ttggctgtaa agggtagttt tcttcccatg catctttcag gagagtgaag 480atagacacca aacccac497<210>36<211>3099<212>DNA<213>未知<220>
<223>未知生物的说明灵长类动物；推测为人(Homo sapiens)<220>
<22l>CDS<222>(1)..(3096)<220>
<22l>mat_肽<222>(52)..(3096)<220>
<221>misc_特征<222>(725)<223>Xaa翻译取决于遗传密码<400>36atg ctg acc tgc att ttc ctg cta ata tct ggt tcc tgt gag tta tgc 48Met Leu Thr Cys Ile Phe Leu Leu Ile Ser Gly Ser Cys Glu Leu Cys-15 -10 -5gcc gaa gaa aat ttt tct aga agc tat cct tgt gat gag aaa aag caa 96Ala Glu Glu Asn Phe Ser Arg Ser Tyr Pro Cys Asp Glu Lys Lys Gln-1 l 5 10 15aat gac tca gtt att gca gag tgc agc aat cgt cga cta cag gaa gtt144Asn Asp Ser Val Ile Ala Glu Cys Ser Asn Arg Arg Leu Gln Glu Val20 25 30
ccc caa acg gtg ggc aaa tat gtg aca gaa cta gac ctg tct gat aat192Pro Gln Thr Val Gly Lys Tyr Val Thr Glu Leu Asp Leu Ser Asp Asn35 40 45ttc atc aca cac ata acg aat gaa tca ttt caa ggg ctg caa aat ctc240Phe Ile Thr His Ile Thr Asn Glu Ser Phe Gln G1y Leu Gln Asn Leu50 55 60act aaa ata aat cta aac cac aac ccc aat gta cag cac cag aac gga288Thr Lys Ile Asn Leu Asn His Asn Pro Asn Val Gln His Gln Asn Gly65 70 75aat ccc ggt ata caa tca aat ggc ttg aat atc aca gac ggg gca ttc336Asn Pro Gly Ile Gln Ser Asn Gly Leu Asn Ile Thr Asp Gly Ala Phe80 85 90 95ctc aac cta aaa aac cta agg gag tta ctg ctt gaa gac aac cag tta384Leu Asn Leu Lys Asn Leu Arg Glu Leu Leu Leu Glu Asp Asn Gln Leu100 105 110ccc caa ata ccc tct ggt ttg cca gag tct ttg aca gaa ctt agt cta432Pro Gln Ile Pro Ser Gly Leu Pro Glu Ser Leu Thr Glu Leu Ser Leu115 120 125att caa aac aat ata tac aac ata act aaa gag ggc att tca aga ctt480Ile Gln Asn Asn Ile Tyr Asn Ile Thr Lys Glu Gly Ile Ser Arg Leu130 135 140ata aac ttg aaa aat ctc tat ttg gcc tgg aac tgc tat ttt aac aaa528Ile Asn Leu Lys Asn Leu Tyr Leu Ala Trp Asn Cys Tyr Phe Asn Lys145 150 155gtt tgc gag aaa act aac ata gaa gat gga gta ttt gaa acg ctg aca576Val Cys Glu Lys Thr Asn Ile Glu Asp Gly Val Phe Glu Thr Leu Thr160 165 170 175aat ttg gag ttg cta tca cta tct ttc aat tct ctt tca cat gtg cca624Asn Leu Glu Leu Leu Ser Leu Ser Phe Asn Ser Leu Ser His Val Pro180 185 190ccc aaa ctg cca agc tcc cta cgc aaa ctt ttt ctg agc aac acc cag672Pro Lys Leu Pro Ser Ser Leu Arg Lys Leu Phe Leu Ser Asn Thr Gln195 200 205atc aaa tac att agt gaa gaa gat ttc aag gga ttg ata aat tta aca720Ile Lys Tyr Ile Ser Glu Glu Asp Phe Lys Gly Leu Ile Asn Leu Thr210 215 220tta cta gat tta agc ggg aac tgt ccg agg tgc ttc aat gcc cca ttt768Leu Leu Asp Leu Ser Gly Asn Cys Pro Arg Cys Phe Asn Ala Pro Phe225 230 235cca tgc gtg cct tgt gat ggt ggt gct tca att aat ata gat cgt ttt816Pro Cys Val Pro Cys Asp Gly Gly Ala Ser Ile Asn Ile Asp Arg Phe240 245 250 255gct ttt caa aac ttg acc caa ctt cga tac cta aac ctc tct agc act864
Ala Phe Gln Asn Leu Thr Gln Leu Arg Tyr Leu Asn Leu Ser Ser Thr260 265 270tcc ctc agg aag att aat gct gcc tgg ttt aaa aat atg cct cat ctg 912Ser Leu Arg Lys Ile Asn Ala Ala Trp Phe Lys Asn Met Pro His Leu275 280 285aag gtg ctg gat ctt gaa ttc aac tat tta gtg gga gaa ata gcc tct 960Lys Val Leu Asp Leu Glu Phe Asn Tyr Leu Val Gly Glu Ile Ala Ser290 295 300ggg gca ttt tta acg atg ctg ccc cgc tta gaa ata ctt gac ttg tct1008Gly Ala Phe Leu Thr Met Leu Pro Arg Leu Glu Ile Leu Asp Leu Ser305 310 315ttt aac tat ata aag ggg agt tat cca cag cat att aat att tcc aga1056Phe Asn Tyr Ile Lys Gly Ser Tyr Pro Gln His Ile Asn Ile Ser Arg320 325 330 335aac ttc tct aaa ctt ttg tct cta cgg gca ttg cat tta aga ggt tat1104Asn Phe Ser Lys Leu Leu Ser Leu Arg Ala Leu His Leu Arg Gly Tyr340 345 350gtg ttc cag gaa ctc aga gaa gat gat ttc cag ccc ctg atg cag ctt1152Val Phe Gln Glu Leu Arg Glu Asp Asp Phe Gln Pro Leu Met Gln Leu355 360 365cca aac tta tcg act atc aac ttg ggt att aat ttt att aag caa atc1200Pro Asn Leu Ser Thr Ilc Asn Leu Gly Ile Asn Phe Ile Lys Gln Ile370 375 380gat ttc aaa ctt ttc caa aat ttc tcc aat ctg gaa att att tac ttg1248Asp Phe Lys Leu Phe Gln Asn Phe Ser Asn Leu Glu Ile Ile Tyr Leu385 390 395tca gaa aac aga ata tca ccg ttg gta aaa gat acc cgg cag agt tat1296Ser Glu Asn Arg Ile Ser Pro Leu Val Lys Asp Thr Arg Gln Ser Tyr400 405 410 415gca aat agt tcc tct ttt caa cgt cat atc cgg aaa cga cgc tca aca1344Ala Asn Ser Ser Ser Phe Gln Arg His Ile Arg Lys Arg Arg Ser Thr420 425 430gat ttt gag ttt gac cca cat tcg aac ttt tat cat ttc acc cgt cct1392Asp Phe Glu Phe Asp Pro His Ser Asn Phe Tyr His Phe Thr Arg Pro435 440 445tta ata aag cca caa tgt gct gct tat gga aaa gcc tta gat tta agc1440Leu Ile Lys Pro Gln Cys Ala Ala Tyr Gly Lys Ala Leu Asp Leu Ser450 455 460ctc aac agt att ttc ttc att ggg cca aac caa ttt gaa aat ctt cct1488Leu Asn Ser Ile Phe Phe Ile Gly Pro Asn Gln Phe Glu Asn Leu Pro465 470 475gac att gcc tgt tta aat ctg tct gca aat agc aat gct caa gtg tta1536Asp Ile Ala Cys Leu Asn Leu Ser Ala Asn Ser Asn Ala Gln Val Leu
480 485490 495agt gga act gaa ttt tca gcc att cct cat gtc aaa tat ttg gat ttg1584Ser Gly Thr Glu Phe Ser Ala Ile Pro His Val Lys Tyr Leu Asp Leu500 505 510aca aac aat aga cta gac ttt gat aat gct agt gct ctt act gaa ttg1632Thr Asn Asn Arg Leu Asp Phe Asp Asn Ala Ser Ala Leu Thr Glu Leu515 520 525tcc gac ttg gaa gtt cta gat ctc agc tat aat tca cac tat ttc aga1680Ser Asp Leu Glu Val Leu Asp Leu Ser Tyr Asn Ser His Tyr Phe Arg530 535 540ata gca ggc gta aca cat cat cta gaa ttt att caa aat ttc aca aat1728Ile Ala Gly Val Thr His His Leu Glu Phe Ile Gln Asn Phe Thr Asn545 550 555cta aaa gtt tta aac ttg agc cac aac aac att tat act tta aca gat1776Leu Lys Val Leu Asn Leu Ser His Asn Asn Ile Tyr Thr Leu Thr Asp560 565 570 575aag tat aac ctg gaa agc aag tcc ctg gta gaa tta gtt ttc agt ggc1824Lys Tyr Asn Leu Glu Ser Lys Ser Leu Val Glu Leu Val Phe Ser Gly580 585 590aat cgc ctt gac att ttg tgg aat gat gat gac aac agg tat atc tcc1872Asn Arg Leu Asp Ile Leu Trp Asn Asp Asp Asp Asn Arg Tyr Ile Ser595 600 605att ttc aaa ggt ctc aag aat ctg aca cgt ctg gat tta tcc ctt aat1920Ile Phe Lys Gly Leu Lys Asn Leu Thr Arg Leu Asp Leu Ser Leu Asn610 615 620agg ctc aag cac atc cca aat gaa gca ttc ctt aat ttg cca gcg agt1968Arg Leu Lys His Ile Pro Asn Glu Ala Phe Leu Asn Leu Pro Ala Ser625 630 635ctc act gaa cta cat ata aat gat aat atg tta aag ttt ttt aac tgg2016Leu Thr Glu Leu His Ile Asn Asp Asn Met Leu Lys Phe Phe Asn Trp640 645 650 655aca tta ctc cag cag ttt cct cgt ctc gag ttg ctt gac tta cgt gga2064Thr Leu Leu Gln Gln Phe Pro Arg Leu Glu Leu Leu Asp Leu Arg Gly660 665 670aac aaa cta ctc ttt tta act gat agc cta tct gac ttt aca tct tcc2112Asn Lys Leu Leu Phe Leu Thr Asp Ser Leu Ser Asp Phe Thr Ser Ser675 680 685ctt cgg aca ctg ctg ctg agt cat aac agg att tcc cac cta ccc tct2160Leu Arg Thr Leu Leu Leu Ser His Asn Arg Ile Ser His Leu Pro Ser690 695 700ggc ttt ctt tct gaa gtc agt agt ctg aag cac ctc gat tta agt tcc2208Gly Phe Leu Ser Glu Val Ser Ser Leu Lys His Leu Asp Leu Ser Ser705 710 715
aat ctg cta aaa aca atm aac aaa tcc gca ctt gaa act aag acc acc 2256Asn Leu Leu Lys Thr Xaa Asn Lys Ser Ala Leu Glu Thr Lys Thr Thr720 725 730 735acc aaa tta tct atg ttg gaa cta cac gga aac ccc ttt gaa tgc acc2304Thr Lys Leu Ser Met Leu Glu Leu His Gly Asn Pro Phe Glu Cys Thr740 745 750tgt gac att gga gat ttc cga aga tgg atg gat gaa cat ctg aat gtc2352Cys Asp Ile Gly Asp Phe Arg Arg Trp Met Asp Glu His Leu Asn Val755 760 765aaa att ccc aga ctg gta gat gtc att tgt gcc agt cct ggg gat caa2400Lys Ile Pro Arg Leu Val Asp Val Ile Cys Ala Ser Pro Gly Asp Gln770 775 780aga ggg aag agt att gtg agt ctg gag cta aca act tgt gtt tca gat2448Arg Gly Lys Ser Ile Val Ser Leu Glu Leu Thr Thr Cys Val Ser Asp785 790 795gtc act gca gtg ata tta ttt ttc ttc acg ttc ttt atc acc acc atg2496Val Thr Ala Val Ile Leu Phe Phe Phe Thr Phe Phe Ile Thr Thr Met800 805 810 815gtt atg ttg gct gcc ctg gct cac cat ttg ttt tac tgg gat gtt tgg2544Val Met Leu Ala Ala Leu Ala His His Leu Phe Tyr Trp Asp Val Trp820 825 830ttt ata tat aat gtg tgt tta gct aag tta aaa ggc tac agg tct ctt2592Phe Ile Tyr Asn Val Cys Leu Ala Lys Leu Lys Gly Tyr Arg Ser Leu835 840 845tcc aca tcc caa act ttc tat gat gct tac att tct tat gac acc aaa2640Ser Thr Ser Gln Thr Phe Tyr Asp Ala Tyr Ile Ser Tyr Asp Thr Lys850 855 860gat gcc tct gtt act gac tgg gtg ata aat gag ctg cgc tac cac ctt2688Asp Ala Ser Val Thr Asp Trp Val Ile Asn Glu Leu Arg Tyr His Leu865 870 875gaa gag agc cga gac aaa aac gtt ctc ctt tgt cta gag gag agg gat2736Glu Glu Ser Arg Asp Lys Asn Val Leu Leu Cys Leu Glu Glu Arg Asp880 885 890 895tgg gac ccg gga ttg gcc atc atc gac aac ctc atg cag agc atc aac2784Trp Asp Pro Gly Leu Ala Ile Ile Asp Asn Leu Met Gln Ser Ile Asn900 905 910caa agc aag aaa aca gta ttt gtt tta acc aaa aaa tat gca aaa agc2832Gln Ser Lys Lys Thr Val Phe Val Leu Thr Lys Lys Tyr Ala Lys Ser915 920 925tgg aac ttt aaa aca gct ttt tac ttg gcc ttg cag agg cta atg ggt2880Trp Asn Phe Lys Thr Ala Phe Tyr Leu Ala Leu Gln Arg Leu Met Gly930 935 940
gag aac atg gat gtg att ata ttt atc ctg ctg gag cca gtg tta cag2928Glu Asn Met Asp Val Ile Ile Phe Ile Leu Leu Glu Pro Val Leu Gln945 950 955cat tct ccg tat ttg agg cta cgg cag cgg atc tgt aag agc tcc atc2976His Ser Pro Tyr Leu Arg Leu Arg Gln Arg Ile Cys Lys Ser Ser Ile960 965 970 975ctc cag tgg cct gac aac ccg aag gca gaa ggc ttg ttt tgg caa act3024Leu Gln Trp Pro Asp Asn Pro Lys Ala Glu Gly Leu Phe Trp Gln Thr980 985 990ctg aga aat gtg gtc ttg act gaa aat gat tca cgg tat aac aat atg3072Leu Arg Asn Val Val Leu Thr Glu Asn Asp Ser Arg Tyr Asn Asn Met99510001005tat gtc gat tcc att aag caa tac taa3099Tyr Val Asp Ser Ile Lys Gln Tyr10101015<210>37<211>1032<212>PRT<213>未知<400>37Met Leu Thr Cys Ile Phe Leu Leu Ile Ser Gly Ser Cys Glu Leu Cys-15 -10 -5Ala Glu Glu Asn Phe Ser Arg Ser Tyr Pro Cys Asp Glu Lys Lys Gln-1 1 5 10 15Asn Asp Ser Val Ile Ala Glu Cys Ser Asn Arg Arg Leu Gln Glu Val20 25 30Pro Gln Thr Val Gly Lys Tyr Val Thr Glu Leu Asp Leu Ser Asp Asn35 40 45Phe Ile Thr His Ile Thr Asn Glu Ser Phe Gln Gly Leu Gln Asn Leu50 55 60Thr Lys Ile Asn Leu Asn His Asn Pro Asn Val Gln His Gln Asn Gly65 70 75Asn Pro Gly Ile Gln Ser Asn Gly Leu Asn Ile Thr Asp Gly Ala Phe80 85 90 95Leu Asn Leu Lys Asn Leu Arg Glu Leu Leu Leu Glu Asp Asn Gln Leu100 105 110Pro Gln Ile Pro Ser Gly Leu Pro Glu Ser Leu Thr Glu Leu Ser Leu115 120 125Ile Gln Asn Asn Ile Tyr Asn Ile Thr Lys Glu Gly Ile Ser Arg Leu130 135 140
Ile Asn Leu Lys Asn Leu Tyr Leu Ala Trp Asn Cys Tyr Phe Asn Lys145 150 155Val Cys Glu Lys Thr Asn Ile Glu Asp Gly Val Phe Glu Thr Leu Thr160 165 170 175Asn Leu Glu Leu Leu Ser Leu Ser Phe Asn Ser Leu Ser His Val Pro180 185 190Pro Lys Leu Pro Ser Ser Leu Arg Lys Leu Phe Leu Ser Asn Thr Gln195 200 205Ile Lys Tyr Ile Ser Glu Glu Asp Phe Lys Gly Leu Ile Asn Leu Thr210 215 220Leu Leu Asp Leu Ser Gly Asn Cys Pro Arg Cys Phe Asn Ala Pro Phe225 230 235Pro Cys Val Pro Cys Asp Gly Gly Ala Ser Ile Asn Ile Asp Arg Phe240 245 250 255Ala Phe Gln Asn Leu Thr Gln Leu Arg Tyr Leu Asn Leu Ser Ser Thr260 265 270Ser Leu Arg Lys Ile Ash Ala Ala Trp Phe Lys Asn Met Pro His Leu275 280 285Lys Val Leu Asp Leu Glu Phe Asn Tyr Leu Val Gly Glu Ile Ala Ser290 295 300Gly Ala Phe Leu Thr Met Leu Pro Arg Leu Glu Ile Leu Asp Leu Ser305 310 315Phe Asn Tyr Ile Lys Gly Ser Tyr Pro Gln His Ile Asn Ile Ser Arg320 325 330 335Asn Phe Ser Lys Leu Leu Ser Leu Arg Ala Leu His Leu Arg Gly Tyr340 345 350Val Phe Gln Glu Leu Arg Glu Asp Asp Phe Gln Pro Leu Met Gln Leu355 360 365Pro Asn Leu Ser Thr Ile Asn Leu Gly Ile Asn Phe Ile Lys Gln Ile370 375 380Asp Phe Lys Leu Phe Gln Asn Phe Ser Asn Leu Glu Ile Ile Tyr Leu385 390 395Ser Glu Asn Arg Ile Ser Pro Leu Val Lys Asp Thr Arg Gln Ser Tyr400 405 410 415Ala Asn Ser Ser Ser Phe Gln Arg His Ile Arg Lys Arg Arg Ser Thr420 425 430Asp Phe Glu Phe Asp Pro His Ser Asn Phe Tyr His Phe Thr Arg Pro435 440 445
Leu Ile Lys Pro Gln Cys Ala Ala Tyr Gly Lys Ala Leu Asp Leu Ser450 455 460Leu Asn Ser Ile Phe Phe Ile Gly Pro Asn Gln Phe Glu Asn Leu Pro465 470 475Asp Ile Ala Cys Leu Asn Leu Ser Ala Asn Ser Asn Ala Gln Val Leu480 485 490 495Ser Gly Thr Glu Phe Ser Ala Ile Pro His Val Lys Tyr Leu Asp Leu500 505 510Thr Asn Asn Arg Leu Asp Phe Asp Asn Ala Ser Ala Leu Thr Glu Leu515 520 525Ser Asp Leu Glu Val Leu Asp Leu Ser Tyr Asn Ser His Tyr Phe Arg530 535 540Ile Ala Gly Val Thr His His Leu Glu Phe Ile Gln Asn Phe Thr Asn545 550 555Leu Lys Val Leu Asn Leu Ser His Asn Asn Ile Tyr Thr Leu Thr Asp560 565 570 575Lys Tyr Asn Leu Glu Ser Lys Ser Leu Val Glu Leu Val Phe Ser Gly580 585 590Asn Arg Leu Asp Ile Leu Trp Asn Asp Asp Asp Asn Arg Tyr Ile Ser595 600 605Ile Phe Lys Gly Leu Lys Asn Leu Thr Arg Leu Asp Leu Ser Leu Asn610 615 620Arg Leu Lys His Ile Pro Asn Glu Ala Phe Leu Asn Leu Pro Ala Ser625 630 635Leu Thr Glu Leu His Ile Asn Asp Asn Met Leu Lys Phe Phe Asn Trp640 645 650 655Thr Leu Leu Gln Gln Phe Pro Arg Leu Glu Leu Leu Asp Leu Arg Gly660 665 670Asn Lys Leu Leu Phe Leu Thr Asp Ser Leu Ser Asp Phe Thr Ser Ser675 680 685Leu Arg Thr Leu Leu Leu Ser His Asn Arg Ile Ser His Leu Pro Ser690 695 700Gly Phe Leu Ser Glu Val Ser Ser Leu Lys His Leu Asp Leu Ser Ser705 710 715Asn Leu Leu Lys Thr Xaa Asn Lys Ser Ala Leu Glu Thr Lys Thr Thr720 725 730 735Thr Lys Leu Ser Met Leu Glu Leu His Gly Asn Pro Phe Glu Cys Thr740 745 750
Cys Asp Ile Gly Asp Phe Arg Arg Trp Met Asp Glu His Leu Asn Val755 760 765Lys Ile Pro Arg Leu Val Asp Val Ile Cys Ala Ser Pro Gly Asp Gln770 775 780Arg Gly Lys Ser Ile Val Ser Leu Glu Leu Thr Thr Cys Val Ser Asp785 790 795Val Thr Ala Val Ile Leu Phe Phe Phe Thr Phe Phe Ile Thr Thr Met800 805 810 815Val Met Leu Ala Ala Leu Ala His His Leu Phe Tyr Trp Asp Val Trp820 825 830Phe Ile Tyr Asn Val Cys Leu Ala Lys Leu Lys Gly Tyr Arg Ser Leu835 840 845Ser Thr Ser Gln Thr Phe Tyr Asp Ala Tyr Ile Ser Tyr Asp Thr Lys850 855 860Asp Ala Ser Val Thr Asp Trp Val Ile Asn Glu Leu Arg Tyr His Leu865 870 875Glu Glu Ser Arg Asp Lys Asn Val Leu Leu Cys Leu Glu Glu Arg Asp880 885 890 895Trp Asp Pro Gly Leu Ala Ile Ile Asp Asn Leu Met Gln Ser Ile Asn900 905 910Gln Sar Lys Lys Thr Val Phe Val Leu Thr Lys Lys Tyr Ala Lys Ser915 920 925Trp Asn Phe Lys Thr Ala Phe Tyr Leu Ala Leu Gln Arg Leu Met Gly930 935 940Glu Asn Met Asp Val Ile Ile Phe Ile Leu Leu Glu Pro Val Leu Gln945 950 955His Ser Pro Tyr Leu Arg Leu Arg Gln Arg Ile Cys Lys Ser Ser Ile960 965 970 975Leu Gln Trp Pro Asp Asn Pro Lys Ala Glu Gly Leu Phe Trp Gln Thr980 985 990Leu Arg Asn Val Val Leu Thr Glu Asn Asp Ser Arg Tyr Asn Asn Met995 10001005Tyr Val Asp Ser Ile Lys Gln Tyr10101015<210>38<211>3046<212>DNA<213>未知
<220>
<223>未知生物的说明灵长类动物；推测为人(Homo sapiens)<220>
<221>CDS<222>(111)..(2543)<220>
<221>mat_肽<222>(168)..(2543)<400>38gaatcatcca cgcacctgca gctctgctga gagagtgcaa gccgtggggg ttttgagctc 60atcttcatca ttcatatgag gaaataagtg gtaaaatcct tggaaataca atg aga 116Met Argctc atc aga aac att tac ata ttt tgt agt att gtt atg aca gca gag164Leu Ile Arg Asn Ile Tyr Ile Phe Cys Ser Ile Val Met Thr Ala Glu-15 -10 -5ggt gat gct cca gag ctg cca gaa gaa agg gaa ctg atg acc aac tgc212Gly Asp Ala Pro Glu Leu Pro Glu Glu Arg Glu Leu Met Thr Asn Cys-1 1 5 10 15tcc aac atg tct cta aga aag gtt ccc gca gac ttg acc cca gcc aca260Ser Asn Met Ser Leu Arg Lys Val Pro Ala Asp Leu Thr Pro Ala Thr20 25 30acg aca ctg gat tta tcc tat aac ctc ctt ttt caa ctc cag agt tca308Thr Thr Leu Asp Leu Ser Tyr Asn Leu Leu Phe Gln Leu Gln Ser Ser35 40 45gat ttt cat tct gtc tcc aaa ctg aga gtt ttg att cta tgc cat aac356Asp Phe His Ser Val Ser Lys Leu Arg Val Leu Ile Leu Cys His Asn50 55 60aga att caa cag ctg gat ctc aaa acc ttt gaa ttc aac aag gag tta404Arg Ile Gln Gln Leu Asp Leu Lys Thr Phe Glu Phe Asn Lys Glu Leu65 70 75aga tat tta gat ttg tct aat aac aga ctg aag agt gta act tgg tat452Arg Tyr Leu Asp Leu Ser Asn Asn Arg Leu Lys Ser Val Thr Trp Tyr80 85 90 95tta ctg gca ggt ctc agg tat tta gat ctt tct ttt aat gac ttt gac500Leu Leu Ala Gly Leu Arg Tyr Leu Asp Leu Ser Phe Asn Asp Phe Asp100 105 110acc atg cct atc tgt gag gaa gct ggc aac atg tca cac ctg gaa atc548Thr Met Pro Ile Cys Glu Glu Ala Gly Asn Met Ser His Leu Glu Ile115 120 125cta ggt ttg agt ggg gca aaa ata caa aaa tca gat ttc cag aaa att596Leu Gly Leu Ser Gly Ala Lys Ile Gln Lys Ser Asp Phe Gln Lys Ile
130 135 140gct cat ctg cat cta aat act gtc ttc tta gga ttc aga act ctt cct644Ala His Leu His Leu Asn Thr Val Phe Leu Gly Phe Arg Thr Leu Pro145 150 155cat tat gaa gaa ggt agc ctg ccc atc tta aac aca aca aaa ctg cac692His Tyr Glu Glu Gly Ser Leu Pro Ile Leu Asn Thr Thr Lys Leu His160 165 170 175att gtt tta cca atg gac aca aat ttc tgg gtt ctt ttg cgt gat gga740Ile Val Leu Pro Met Asp Thr Asn Phe Trp Val Leu Leu Arg Asp Gly180 185 190atc aag act tca aaa ata tta gaa atg aca aat ata gat ggc aaa agc788Ile Lys Thr Ser Lys Ile Leu Glu Met Thr Asn Ile Asp Gly Lys Ser195 200 205caa ttt gta agt tat gaa atg caa cga aat ctt agt tta gaa aat gct836Gln Phe Val Ser Tyr Glu Met Gln Arg Asn Leu Ser Leu Glu Asn Ala210 215 220aag aca tcg gtt cta ttg ctt aat aaa gtt gat tta ctc tgg gac gac884Lys Thr Ser Val Leu Leu Leu Asn Lys Val Asp Leu Leu Trp Asp Asp225 230 235ctt ttc ctt atc tta caa ttt gtt tgg cat aca tca gtg gaa cac ttt932Leu Phe Leu Ile Leu Gln Phe Val Trp His Thr Ser Val Glu His Phe240 245 250 255cag atc cga aat gtg act ttt ggt ggt aag gct tat ctt gac cac aat980Gln Ile Arg Asn Val Thr Phe Gly Gly Lys Ala Tyr Leu Asp His Asn260 265 270tca ttt gac tac tca aat act gta atg aga act ata aaa ttg gag cat 1028Ser Phe Asp Tyr Ser Asn Thr Val Met Arg Thr Ile Lys Leu Glu His275 280 285gta cat ttc aga gtg ttt tac att caa cag gat aaa atc tat ttg ctt 1076Val His Phe Arg Val Phe Tyr Ile Gln Gln Asp Lys Ile Tyr Leu Leu290 295 300ttg acc aaa atg gac ata gaa aac ctg aca ata tca aat gca caa atg 1124Leu Thr Lys Met Asp Ile Glu Asn Leu Thr Ile Ser Asn Ala Gln Met305 310 315cca cac atg ctt ttc ccg aat tat cct acg aaa ttc caa tat tta aat 1172Pro His Met Leu Phe Pro Asn Tyr Pro Thr Lys Phe Gln Tyr Leu Asn320 325 330 335ttt gcc aat aat atc tta aca gac gag ttg ttt aaa aga act atc caa 1220Phe Ala Asn Asn Ile Leu Thr Asp Glu Leu Phe Lys Arg Thr Ile Gln340 345 350ctg cct cac ttg aaa act ctc att ttg aat ggc aat aaa ctg gag aca 1268Leu Pro His Leu Lys Thr Leu Ile Leu Asn Gly Asn Lys Leu Glu Thr355 360 365
ctt tct tta gta agt tgc ttt gct aac aac aca ccc ttg gaa cac ttg1316Leu Ser Leu Val Ser Cys Phe Ala Asn Asn Thr Pro Leu Glu His Leu370 375 380gat ctg agt caa aat cta tta caa cat aaa aat gat gaa aat tgc tca1364Asp Leu Ser Gln Asn Leu Leu Gln His Lys Asn Asp Glu Asn Cys Ser385 390 395tgg cca gaa act gtg gtc aat atg aat ctg tca tac aat aaa ttg tct1412Trp Pro Glu Thr Val Val Asn Met Asn Leu Ser Tyr Asn Lys Leu Ser400 405 410 415gat tct gtc ttc agg tgc ttg ccc aaa agt att caa ata ctt gac cta1460Asp Ser Val Phe Arg Cys Leu Pro Lys Ser Ile Gln Ile Leu Asp Leu420 425 430aat aat aac caa atc caa act gta cct aaa gag act att cat ctg atg1508Asn Asn Asn Gln Ile Gln Thr Val Pro Lys Glu Thr Ile His Leu Met435 440 445gcc tta cga gaa cta aat att gca ttt aat ttt cta act gat ctc cct1556Ala Leu Arg Glu Leu Asn Ile Ala Phe Asn Phe Leu Thr Asp Leu Pro450 455 460gga tgc agt cat ttc agt aga ctt tca gtt ctg aac att gaa atg aac1604Gly Cys Ser His Phe Sar Arg Leu Ser Val Leu Asn Ile Glu Met Asn465 470 475ttc att ctc agc cca tct ctg gat ttt gtt cag agc tgc cag gaa gtt1652Phe Ile Leu Set Pro Ser Leu Asp Phe Val Gln Ser Cys Gln Glu Val480 485 490 495aaa act cta aat gcg gga aga aat cca ttc cgg tgt acc tgt gaa tta1700Lys Thr Leu Asn Ala Gly Arg Asn Pro Phe Arg Cys Thr Cys Glu Leu500 505 510aaa aat ttc att cag ctt gaa aca tat tca gag gtc atg atg gtt gga1748Lys Asn Phe Ile Gln Leu Glu Thr Tyr Ser Glu Val Met Met Val Gly515 520 525tgg tca gat tca tac acc tgt gaa tac cct tta aac cta agg gga act1796Trp Ser Asp Ser Tyr Thr Cys Glu Tyr Pro Leu Asn Leu Arg Gly Thr530 535 540agg tta aaa gac gtt cat ctc cac gaa tta tct tgc aac aca gct ctg1844Arg Leu Lys Asp Val His Leu His Glu Leu Ser Cys Asn Thr Ala Leu545 550 555ttg att gtc acc att gtg gtt att atg cta gtt ctg ggg ttg gct gtg1892Leu Ile Val Thr Ile Val Val Ile Met Leu Val Leu Gly Leu Ala Val560 565 570 575gcc ttc tgc tgt ctc cac ttt gat ctg ccc tgg tat ctc agg atg cta1940Ala Phe Cys Cys Leu His Phe Asp Leu Pro Trp Tyr Leu Arg Met Leu5850585 590
ggt caa tgc aca caa aca tgg cac agg gtt agg aaa aca acc caa gaa1988Gly Gln Cys Thr Gln Thr Trp His Arg Val Arg Lys Thr Thr Gln Glu595 600 605caa ctc aag aga aat gtc cga ttc cac gca ttt att tca tac agt gaa2036Gln Leu Lys Arg Asn Val Arg Phe His Ala Phe Ile Ser Tyr Ser Glu610 615 620cat gat tct ctg tgg gtg aag aat gaa ttg atc ccc aat cta gag aag2084His Asp Set Leu Trp Val Lys Asn Glu Leu Ile Pro Asn Leu Glu Lys625 630 635gaa gat ggt tct atc ttg att tgc ctt tat gaa agc tac ttt gac cct2132Glu Asp Gly Ser Ile Leu Ile Cys Leu Tyr Glu Ser Tyr Phe Asp Pro640 645 650 655ggc aaa agc att agt gaa aat att gta agc ttc att gag aaa agc tat2180Gly Lys Ser Ile Ser Glu Asn Ile Val Ser Phe Ile Glu Lys Ser Tyr660 665 670aag tcc atc ttt gtt ttg tct ccc aac ttt gtc cag aat gag tgg tgc2228Lys Ser Ile Phe Val Leu Ser Pro Asn Phe Val Gln Asn Glu Trp Cys675 680 685cat tat gaa ttc tac ttt gcc cac cac aat ctc ttc cat gaa aat tct2276His Tyr Glu Phe Tyr Phe Ala His His Asn Leu Phe His Glu Asn Ser690 695 700gat cat ata att ctt atc tta ctg gaa ccc att cca ttc tat tgc att2324Asp His Ile Ile Leu Ile Leu Leu Glu Pro Ile Pro Phe Tyr Cys Ile705 710 715ccc acc agg tat cat aaa ctg aaa gct ctc ctg gaa aaa aaa gca tac2372Pro Thr Arg Tyr His Lys Leu Lys Ala Leu Leu Glu Lys Lys Ala Tyr720 725 730 735ttg gaa tgg ccc aag gat agg cgt aaa tgt ggg ctt ttc tgg gca aac2420Leu Glu Trp Pro Lys Asp Arg Arg Lys Cys Gly Leu Phe Trp Ala Asn740 745 750ctt cga gct gct att aat gtt aat gta tta gcc acc aga gaa atg tat2468Leu Arg Ala Ala Ile Asn Val Asn Val Leu Ala Thr Arg Glu Met Tyr755 760 765gaa ctg cag aca ttc aca gag tta aat gaa gag tct cga ggt tct aca2516Glu Leu Gln Thr Phe Thr Glu Leu Asn Glu glu Ser Arg Gly Ser Thr770 775 780atc tct ctg atg aga aca gat tgt cta taaaatccca cagtccttgg 2563Ile Ser Leu Met Arg Thr Asp Cys Leu785 790gaagttgggg accacataca ctgttgggat gtacattgat acaaccttta tgatggcaat 2623ttgacaatat ttattaaaat aaaaaatggt tattcccttc atatcagttt ctagaaggat 2683ttctaagaat gtatcctata gaaacacctt cacaagttta taagggctta tggaaaaagg 2743
tgttcatccc aggattgttt ataatcatga aaaatgtggc caggtgcagt ggctcactct 2803tgtaatccca gcactatggg aggccaaggt gggtgaccca cgaggtcaag agatggagac 2863catcctggcc aacatggtga aaccctgtct ctactaaaaa tacaaaaatt agctgggcgt 2923gatggtgcac gcctgtagtc ccagctactt gggaggctga ggcaggagaa tcgcttgaac 2983ccgggaggtg gcagttgcag tgagctgaga tcgagccact gcactccagc ctggtgacag 3043agc 3046<210>39<211>811<212>PRT<213>未知<400>39Met Arg Leu Ile Arg Asn Ile Tyr Ile Phe Cys Ser Ile Val Met Thr-15 -10 -5Ala Glu Gly Asp Ala Pro Glu Leu Pro Glu Glu Arg Glu Leu Met Thr-1 1 5 10Asn Cys Ser Asn Met Ser Leu Arg Lys Val Pro Ala Asp Leu Thr Pro15 20 25Ala Thr Thr Thr Leu Asp Leu Ser Tyr Asn Leu Leu Phe Gln Leu Gln30 35 40 45Ser Ser Asp Phe His Ser Val Ser Lys Leu Arg Val Leu Ile Leu Cys50 55 60His Asn Arg Ile Gln Gln Leu Asp Leu Lys Thr Phe Glu Phe Asn Lys65 70 75Glu Leu Arg Tyr Leu Asp Leu Ser Asn Asn Arg Leu Lys Ser Val Thr80 85 90Trp Tyr Leu Leu Ala Gly Leu Arg Tyr Leu Asp Leu Ser Phe Asn Asp95 100 105Phe Asp Thr Met Pro Ile Cys Glu Glu Ala Gly Asn Met Ser His Leu110 115 120 125Glu Ile Leu Gly Leu Ser Gly Ala Lys Ile Gln Lys Ser Asp Phe Gln130 135 140Lys Ile Ala His Leu His Leu Asn Thr Val Phe Leu Gly Phe Arg Thr145 150 155Leu Pro His Tyr Glu Glu Gly Ser Leu Pro Ile Leu Asn Thr Thr Lys160 165 170Leu His Ile Val Leu Pro Met Asp Thr Asn Phe Trp Val Leu Leu Arg
175 180 185Asp Gly Ile Lys Thr Ser Lys Ile Leu Glu Met Thr Asn Ile Asp Gly190l95 200 205Lys Ser Gln Phe Val Ser Tyr Glu Met Gln Arg Asn Leu Ser Leu Glu210 215 220Asn Ala Lys Thr Ser Val Leu Leu Leu Asn Lys Val Asp Leu Leu Trp225 230 235Asp Asp Leu Phe Leu Ile Leu G1n Phe Val Trp His Thr Ser Val Glu240 245 250His Phe Gln Ile Arg Asn Val Thr Phe Gly Gly Lys Ala Tyr Leu Asp255 260 265His Asn Ser Phe Asp Tyr Ser Asn Thr Val Met Arg Thr Ile Lys Leu270 275 280 285Glu His Val His Phe Arg Val Phe Tyr Ile Gln Gln Asp Lys Ile Tyr290 295 300Leu Leu Leu Thr Lys Met Asp Ile Glu Asn Leu Thr Ile Ser Asn Ala305 310 315Gln Met Pro His Met Leu Phe Pro Asn Tyr Pro Thr Lys Phe Gln Tyr320 325 330Leu Asn Phe Ala Asn Asn Ile Leu Thr Asp Glu Leu Phe Lys Arg Thr335 340 345Ile Gln Leu Pro His Leu Lys Thr Leu Ile Leu Asn Gly Asn Lys Leu350 355 360 365Glu Thr Leu Ser Leu Val Ser Cys Phe Ala Asn Asn Thr Pro Leu Glu370 375 380His Leu Asp Leu Ser Gln Asn Leu Leu Gln His Lys Asn Asp Glu Asn385 390 395Cys Ser Trp Pro Glu Thr Val Val Asn Met Asn Leu Ser Tyr Asn Lys400 405 410Leu Ser Asp Ser Val Phe Arg Cys Leu Pro Lys Ser Ile Gln Ile Leu415 420 425Asp Leu Asn Asn Asn Gln Ile Gln Thr Val Pro Lys Glu Thr Ile His430 435 440 445Leu Met Ala Leu Arg Glu Leu Asn Ile Ala Phe Asn Phe Leu Thr Asp450 455 460Leu Pro Gly Cys Ser His Phe Ser Arg Leu Ser Val Leu Asn Ile Glu465 470 475Met Asn Phe Ile Leu Ser Pro Ser Leu Asp Phe Val Gln Ser Cys Gln
480 485 490Glu Val Lys Thr Leu Asn Ala Gly Arg Asn Pro Phe Arg Cys Thr Cys495 500 505Glu Leu Lys Asn Phe Ile Gln Leu Glu Thr Tyr Ser Glu Val Met Met510 515 520 525Val Gly Trp Ser Asp Ser Tyr Thr Cys Glu Tyr Pro Leu Asn Leu Arg530 535 540Gly Thr Arg Leu Lys Asp Val His Leu His Glu Leu Ser Cys Asn Thr545 550 555Ala Leu Leu Ile Val Thr Ile Val Val Ile Met Leu Val Leu Gly Leu560 565 570Ala Val Ala Phe Cys Cys Leu His Phe Asp Leu Pro Trp Tyr Leu Arg575 580 585Met Leu Gly Gln Cys Thr Gln Thr Trp His Arg Val Arg Lys Thr Thr590 595 600 605Gln Glu Gln Leu Lys Arg Asn Val Arg Phe His Ala Phe Ile Ser Tyr610 615 620Ser Glu His Asp Ser Leu Trp Val Lys Asn Glu Leu Ile Pro Asn Leu625 630 635Glu Lys Glu Asp Gly Ser Ile Leu Ile Cys Leu Tyr Glu Ser Tyr Phe640 645 650Asp Pro Gly Lys Ser Ile Ser Glu Asn Ile Val Ser Phe Ile Glu Lys655 660 665Ser Tyr Lys Ser Ile Phe Val Leu Ser Pro Asn Phe Val Gln Asn Glu670 675 680 685Trp Cys His Tyr Glu Phe Tyr Phe Ala His His Asn Leu Phe His Glu690 695 700Asn Ser Asp His Ile Ile Leu Ile Leu Leu Glu Pro Ile Pro Phe Tyr705 710 715Cys Ile Pro Thr Arg Tyr His Lys Leu Lys Ala Leu Leu Glu Lys Lys720 725 730Ala Tyr Leu Glu Trp Pro Lys Asp Arg Arg Lys Cys Gly Leu Phe Trp735 740 745Ala Asn Leu Arg Ala Ala Ile Asn Val Asn Val Leu Ala Thr Arg Glu750 755 760 765Met Tyr Glu Leu Gln Thr Phe Thr Glu Leu Asn Glu Glu Ser Arg Gly770 775 780Ser Thr Ile Ser Leu Met Arg Thr Asp Cys Leu
785 790<210>40<211>2760<212>DNA<213>未知<220>
<223>未知生物的说明灵长类动物；推测为人(Homo sapiens)<220>
<221>CDS<222>(68)..(2455)<220>
<221>mat_肽<222>(161)..(2455)<220>
<22l>misc_特征<222>(2529)<223>n可以是a，c，g，或t<400>40aagaatttgg actcatatca agatgctctg aagaagaaca accctttagg atagccactg 60caacatc atg acc aaa gac aaa gaa cct att gtt aaa agc ttc cat ttt109Met Thr Lys Asp Lys Glu Pro Ile Val Lys Ser Phe His Phe-30 -25 -20gtt tgc ctt atg atc ata ata gtt gga acc aga atc cag ttc tcc gac157Val Cys Leu Met Ile Ile Ile Val Gly Thr Arg Ile Gln Phe Ser Asp-15 -10 -5gga aat gaa ttt gca gta gac aag tca aaa aga ggt ctt att cat gtt205Gly Asn Glu Phe Ala Val Asp Lys Ser Lys Arg Gly Leu Ile His Val-1 1 5 10 15cca aaa gac cta ccg ctg aaa acc aaa gtc tta gat atg tct cag aac253Pro Lys Asp Leu Pro Leu Lys Thr Lys Val Leu Asp Met Ser Gln Asn20 25 30tac atc gct gag ctt cag gtc tct gac atg agc ttt cta tca gag ttg301Tyr Ile Ala Glu Leu Gln Val Ser Asp Met Ser Phe Leu Ser Glu Leu35 40 45aca gtt ttg aga ctt tcc cat aac aga atc cag cta ctt gat tta agt349Thr Val Leu Arg Leu Ser His Asn Arg Ile Gln Leu Leu Asp Leu Ser50 55 60gtt ttc aag ttc aac cag gat tta gaa tat ttg gat tta tct cat aat397Val Phe Lys Phe Asn Gln Asp Leu Glu Tyr Leu Asp Leu Ser His Asn65 70 75
cag ttg caa aag ata tcc tgc cat cct att gtg agt ttc agg cat tta445Gln Leu Gln Lys Ile Ser Cys His Pro Ile Val Ser Phe Arg His Leu80 85 90 95gat ctc tca ttc aat gat ttc aag gcc ctg ccc atc tgt aag gaa ttt493Asp Leu Ser Phe Asn Asp Phe Lys Ala Leu Pro Ile Cys Lys Glu Phe100 105 110ggc aac tta tca caa ctg aat ttc ttg gga ttg agt gct atg aag ctg541Gly Asn Leu Ser Gln Leu Asn Phe Leu Gly Leu Ser Ala Met Lys Leu115 120 125caa aaa tta gat ttg ctg cca att gct cac ttg cat cta agt tat atc589Gln Lys Leu Asp Leu Leu Pro Ile Ala His Leu His Leu Ser Tyr Ile130 135 140ctt ctg gat tta aga aat tat tat ata aaa gaa aat gag aca gaa agt637Leu Leu Asp Leu Arg Asn Tyr Tyr Ile Lys Glu Asn Glu Thr Glu Ser145 150 155cta caa att ctg aat gca aaa acc ctt cac ctt gtt ttt cac cca act685Leu Gln Ile Leu Asn Ala Lys Thr Leu His Leu Val Phe His Pro Thr160 165 170 175agt tta ttc gct atc caa gtg aac ata tca gtt aat act tta ggg tgc733Ser Leu Phe Ala Ile Gln Val Asn Ile Ser Val Asn Thr Leu Gly Cys180 185 190tta caa ctg act aat att aaa ttg aat gat gac aac tgt caa gtt ttc781Leu Gln Leu Thr Asn Ile Lys Leu Asn Asp Asp Asn Cys Gln Val Phe195 200 205att aaa ttt tta tca gaa ctc acc aga ggt cca acc tta ctg aat ttt829Ile Lys Phe Leu Ser Glu Leu Thr Arg Gly Pro Thr Leu Leu Asn Phe210 215 220acc ctc aac cac ata gaa acg act tgg aaa tgc ctg gtc aga gtc ttt877Thr Leu Asn His Ile Glu Thr Thr Trp Lys Cys Leu Val Arg Val Phe225 230 235caa ttt ctt tgg ccc aaa cct gtg gaa tat ctc aat att tac aat tta925Gln Phe Leu Trp Pro Lys Pro Val Glu Tyr Leu Asn Ile Tyr Asn Leu240 245 250 255aca ata att gaa agc att cgt gaa gaa gat ttt act tat tct aaa acg973Thr Ile Ile Glu Ser Ile Arg Glu Glu Asp Phe Thr Tyr Ser Lys Thr260 265 270aca ttg aaa gca ttg aca ata gaa cat atc acg aac caa gtt ttt ctg 1021Thr Leu Lys Ala Leu Thr Ile Glu His Ile Thr Asn Gln Val Phe Leu275 280 285ttt tca cag aca gct ttg tac acc gtg ttt tct gag atg aac att atg 1069Phe Ser Gln Thr Ala Leu Tyr Thr Val Phe Ser Glu Met Asn Ile Met290 295 300atg tta acc att tca gat aca cct ttt ata cac atg ctg tgt cct cat 1117
Met Leu Thr Ile Ser Asp Thr Pro Phe Ile His Met Leu Cys Pro His305 310 315gca cca agc aca ttc aag ttt ttg aac ttt acc cag aac gtt ttc aca1165Ala Pro Ser Thr Phe Lys Phe Leu Asn Phe Thr Gln Asn Val Phe Thr320 325 330 335gat agt att ttt gaa aaa tgt tcc acg tta gtt aaa ttg gag aca ctt1213Asp Ser Ile Phe Glu Lys Cys Ser Thr Leu Val Lys Leu Glu Thr Leu340 345 350atc tta caa aag aat gga tta aaa gac ctt ttc aaa gta ggt ctc atg1261Ile Leu Gln Lys Asn Gly Leu Lys Asp Leu Phe Lys Val Gly Leu Met355 360 365acg aag gat atg cct tct ttg gaa ata ctg gat gtt agc tgg aat tct1309Thr Lys Asp Met Pro Ser Leu Glu Ile Leu Asp Val Ser Trp Asn Ser370 375 380ttg gaa tct ggt aga cat aaa gaa aac tgc act tgg gtt gag agt ata1357Leu Glu Ser Gly Arg His Lys Glu Asn Cys Thr Trp Val Glu Ser Ile385 390 395gtg gtg tta aat ttg tct tca aat atg ctt act gac tct gtt ttc aga1405Val Val Leu Asn Leu Ser Ser Asn Met Leu Thr Asp Ser Val Phe Arg400 405 410 415tgt tta cct ccc agg atc aag gta ctt gat ctt cac agc aat aaa ata1453Cys Leu Pro Pro Arg Ile Lys Val Leu Asp Leu His Ser Asn Lys Ile420 425 430aag agc gtt cct aaa caa gtc gta aaa ctg gaa gct ttg caa gaa ctc1501Lys Ser Val Pro Lys Gln Val Val Lys Leu Glu Ala Leu Gln Glu Leu435 440 445aat gtt gct ttc aat tct tta act gac ctt cct gga tgt ggc agc ttt1549Asn Val Ala Phe Asn Ser Leu Thr Asp Leu Pro Gly Cys Gly Ser Phe450 455 460agc agc ctt tct gta ttg atc att gat cac aat tca gtt tcc cac cca1597Ser Ser Leu Ser Val Leu Ile Ile Asp His Asn Ser Val Ser His Pro465 470 475tcg gct gat ttc ttc cag agc tgc cag aag atg agg tca ata aaa gca1645Ser Ala Asp Phe Phe Gln Ser Cys Gln Lys Met Arg Ser Ile Lys Ala480 485 490 495ggg gac aat cca ttc caa tgt acc tgt gag cta aga gaa ttt gtc aaa1693Gly Asp Asn Pro Phe Gln Cys Thr Cys Glu Leu Arg Glu Phe Val Lys500 505 510aat ata gac caa gta tca agt gaa gtg tta gag ggc tgg cct gat tct1741Asn Ile Asp Gln Val Ser Ser Glu Val Leu Glu Gly Trp Pro Asp Ser515 520 525tat aag tgt gac tac cca gaa agt tat aga gga agc cca cta aag gac1789Tyr Lys Cys Asp Tyr Pro Glu Ser Tyr Arg Gly Ser Pro Leu Lys Asp
530 535 540ttt cac atg tct gaa tta tcc tgc aac ata act ctg ctg atc gtc acc1837Phe His Met Ser Glu Leu Ser Cys Asn Ile Thr Leu Leu Ile Val Thr545 550 555atc ggt gcc acc atg ctg gtg ttg gct gtg act gtg acc tcc ctc tgc1885Ile Gly Ala Thr Met Leu Val Leu Ala Val Thr Val Thr Ser Leu Cys560 565 570 575atc tac ttg gat ctg ccc tgg tat ctc agg atg gtg tgc cag tgg acc1933Ile Tyr Leu Asp Leu Pro Trp Tyr Leu Arg Met Val Cys Gln Trp Thr580 585 590cag act cgg cgc agg gcc agg aac ata ccc tta gaa gaa ctc caa aga1981Gln Thr Arg Arg Arg Ala Arg Asn Ile Pro Leu Glu Glu Leu Gln Arg595 600 605aac ctc cag ttt cat gct ttt att tca tat agt gaa cat gat tct gcc2029Asn Leu Gln Phe His Ala Phe Ile Ser Tyr Ser Glu His Asp Ser Ala610 615 620tgg gtg aaa agt gaa ttg gta cct tac cta gaa aaa gaa gat ata cag2077Trp Val Lys Ser Glu Leu Val Pro Tyr Leu Glu Lys Glu Asp Ile Gln625 630 635att tgt ctt cat gag agg aac ttt gtc cct ggc aag agc att gtg gaa2125Ile Cys Leu His Glu Arg Asn Phe Val Pro Gly Lys Ser Ile Val Glu640 645 650 655aat atc atc aac tgc att gag aag agt tac aag tcc atc ttt gtt ttg2173Asn Ile Ile Asn Cys Ile Glu Lys Ser Tyr Lys Ser Ile Phe Val Leu660 665 670tct ccc aac ttt gtc cag agt gag tgg tgc cat tac gaa ctc tat ttt2221Ser Pro Asn Phe Val Gln Ser Glu Trp Cys His Tyr Glu Leu Tyr Phe675 680 685gcc cat cac aat ctc ttt cat gaa gga tct aat aac tta atc ctc atc2269Ala His His Asn Leu Phe His Glu Gly ser Asn Asn Leu Ile Leu Ile690 695 700tta ctg gaa ccc att cca cag aac agc att ccc aac aag tac cac aag2317Leu Leu Glu Pro Ile Pro Gln Asn Ser Ile Pro Asn Lys Tyr His Lys705 710 715ctg aag gct ctc atg acg cag cgg act tat ttg cag tgg ccc aag gag2365Leu Lys Ala Leu Met Thr Gln Arg Thr Tyr Leu Gln Trp Pro Lys Glu720 725 730 735aaa agc aaa cgt ggg ctc ttt tgg gct aac att aga gcc gct ttt aat2415Lys Ser Lys Arg Gly Leu Phe Trp Ala Asn Ile Arg Ala Ala Phe Asn740 745 750atg aaa tta aca cta gtc act gaa aac aat gat gtg aaa tct2455Met Lys Leu Thr Leu Val Thr Glu Asn Asn Asp Val Lys Ser755 760 765
taaaaaaatt taggaaattc aacttaagaa accattattt acttggatga tggtgaatag 2515tacagtcgta agtnactgtc tggaggtgcc tccattatcc tcatgccttc aggaaagact 2575taacaaaaac aatgtttcat ctggggaact gagctaggcg gtgaggttag cctgccagtt 2635agagacagcc cagtctcttc tggtttaatc attatgtttc aaattgaaac agtctctttt 2695gagtaaatgc tcagtttttc agctcctctc cactctgctt tcccaaatgg attctgttgg 2755tgaag 2760<210>41<211>796<212>PRT<213>未知<400>41Met Thr Lys Asp Lys Glu Pro Ile Val Lys Ser Phe His Phe Val Cys-30 -25 -20Leu Met Ile Ile Ile Val Gly Thr Arg Ile Gln Phe Ser Asp Gly Asn-15 -10 -5 -1 1Glu Phe Ala Val Asp Lys Ser Lys Arg Gly Leu Ile His Val Pro Lys5 10 15Asp Leu Pro Leu Lys Thr Lys Val Leu Asp Met Ser Gln Asn Tyr Ile20 25 30Ala Glu Leu Gln Val Ser Asp Met Ser Phe Leu Ser Glu Leu Thr Val35 40 45Leu Arg Leu Ser His Asn Arg Ile Gln Leu Leu Asp Leu Ser Val Phe50 55 60 65Lys Phe Asn Gln Asp Leu Glu Tyr Leu Asp Leu Ser His Asn Gln Leu70 75 80Gln Lys Ile Ser Cys His Pro Ile Val Ser Phe Arg His Leu Asp Leu85 90 95Ser Phe Asn Asp Phe Lys Ala Leu Pro Ile Cys Lys Glu Phe Gly Asn100 105 110Leu Ser Gln Leu Asn Phe Leu Gly Leu Ser Ala Met Lys Leu Gln Lys115 120 125Leu Asp Leu Leu Pro Ile Ala His Leu His Leu Ser Tyr Ile Leu Leu130 135 140 145Asp Leu Arg Asn Tyr Tyr Ile Lys Glu Asn Glu Thr Glu Ser Leu Gln150 155 160Ile Leu Asn Ala Lys Thr Leu His Leu Val Phe His Pro Thr Ser Leu
165 170 175Phe Ala Ile Gln Val Asn Ile Ser Val Asn Thr Leu Gly Cys Leu Gln180 185 190Leu Thr Asn Ile Lys Leu Asn Asp Asp Asn Cys Gln Val Phe Ile Lys195 200 205Phe Leu Ser Glu Leu Thr Arg Gly Pro Thr Leu Leu Asn Phe Thr Leu210 215 220 225Asn His Ile Glu Thr Thr Trp Lys Cys Leu Val Arg Val Phe Gln Phe230 235 240Leu Trp Pro Lys Pro Val Glu Tyr Leu Asn Ile Tyr Asn Leu Thr Ile245 250 255Ile Glu Ser Ile Arg Glu Glu Asp Phe Thr Tyr Ser Lys Thr Thr Leu260 265 270Lys Ala Leu Thr Ile Glu His Ile Thr Asn Gln Val Phe Leu Phe Ser275 280 285Gln Thr Ala Leu Tyr Thr Val Phe Ser Glu Met Asn Ile Met Met Leu290 295 300 305Thr Ile Ser Asp Thr Pro Phe Ile His Met Leu Cys Pro His Ala Pro310 315 320Ser Thr Phe Lys Phe Leu Asn Phe Thr Gln Asn Val Phe Thr Asp Ser325 330 335Ile Phe Glu Lys Cys Ser Thr Leu Val Lys Leu Glu Thr Leu Ile Leu340 345 350Gln Lys Asn Gly Leu Lys Asp Leu Phe Lys Val Gly Leu Met Thr Lys355 360 365Asp Met Pro Ser Leu Glu Ile Leu Asp Val Ser Trp Asn Ser Leu Glu370 375 380 385Ser Gly Arg His Lys Glu Asn Cys Thr Trp Val Glu Ser Ile Val Val390 395 400Leu Asn Leu Ser Ser Asn Met Leu Thr Asp Ser Val Phe Arg Cys Leu405 410 415Pro Pro Arg Ile Lys Val Leu Asp Leu His Ser Asn Lys Ile Lys Ser420 425 430Val Pro Lys Gln Val Val Lys Leu Glu Ala Leu Gln Glu Leu Asn Val435 440 445Ala Phe Asn Ser Leu Thr Asp Leu Pro Gly Cys Gly Ser Phe Ser Ser450 455 460 465Leu Ser Val Leu Ile Ile Asp His Asn Ser Val Ser His Pro Ser Ala
470 475 480Asp Phe Phe Gln Ser Cys Gln Lys Met Arg Ser Ile Lys Ala Gly Asp485 490 495Asn Pro Phe Gln Cys Thr Cys Glu Leu Arg Glu Phe Val Lys Asn Ile500 505 510Asp Gln Val Ser Ser Glu Val Leu Glu Gly Trp Pro Asp Ser Tyr Lys515 520 525Cys Asp Tyr Pro Glu Ser Tyr Arg Gly Ser Pro Leu Lys Asp Phe His530 535 540 545Met Ser Glu Leu Ser Cys Asn Ile Thr Leu Leu Ile Val Thr Ile Gly550 555 560Ala Thr Met Leu Val Leu Ala Val Thr Val Thr Ser Leu Cys Ile Tyr565 570 575Leu Asp Leu Pro Trp Tyr Leu Arg Met Val Cys Gln Trp Thr Gln Thr580 585 590Arg Arg Arg Ala Arg Asn Ile Pro Leu Glu Glu Leu Gln Arg Asn Leu595 600 605Gln Phe His Ala Phe Ile Ser Tyr Ser Glu His Asp Ser Ala Trp Val610 615 620 625Lys Ser Glu Leu Val Pro Tyr Leu Glu Lys Glu Asp Ile Gln Ile Cys630 635 640Leu His Glu Arg Asn Phe Val Pro Gly Lys Ser Ile Val Glu Asn Ile645 650 655Ile Asn Cys Ile Glu Lys Ser Tyr Lys Ser Ile Phe Val Leu Ser Pro660 665 670Asn Phe Val Gln Ser Glu Trp Cys His Tyr Glu Leu Tyr Phe Ala His675 680 685His Asn Leu Phe His Glu Gly Ser Asn Asn Leu Ile Leu Ile Leu Leu690 695 700 705Glu Pro Ile Pro Gln Asn Ser Ile Pro Asn Lys Tyr His Lys Leu Lys710 715 720Ala Leu Met Thr Gln Arg Thr Tyr Leu Gln Trp Pro Lys Glu Lys Ser725 730 735Lys Arg Gly Leu Phe Trp Ala Asn Ile Arg Ala Ala Phe Asn Met Lys740 745 750Leu Thr Leu Val Thr Glu Asn Asn Asp Val Lys Ser755 760 765
<210>42<211>3168<212>DNA<213>未知<220>
<223>未知生物的说明灵长类动物；推测为人(Homo sapiens)<220>
<221>CDS<222>(1)..(3165)<220>
<221>mat_肽<222>(144)..(3165)<400>42atg ccc atg aag tgg agt ggg tgg agg tgg agc tgg ggg ccg gcc act 48Met Pro Met Lys Trp Ser Gly Trp Arg Trp Ser Trp Gly Pro Ala Thr-45 -40 -35cac aca gcc ctc cca ccc cca cag ggt ttc tgc cgc agc gcc ctg cac 96His Thr Ala Leu Pro Pro Pro Gln Gly Phe Cys Arg Ser Ala Leu His-30 -25 -20ccg ctg tct ctc ctg gtg cag gcc atc atg ctg gcc atg acc ctg gcc144Pro Leu Ser Leu Leu Val Gln Ala Ile Met Leu Ala Met Thr Leu Ala-15 -10 -5 -1ctg ggt acc ttg cct gcc ttc cta ccc tgt gag ctc cag ccc cac ggc192Leu Gly Thr Leu Pro Ala Phe Leu Pro Cys Glu Leu Gln Pro His Gly1 5 10 15ctg gtg aac tgc aac tgg ctg ttc ctg aag tct gtg ccc cac ttc tcc240Leu Val Asn Cys Asn Trp Leu Phe Leu Lys Ser Val Pro His Phe Ser20 25 30atg gca gca ccc cgt ggc aat gtc acc agc ctt tcc ttg tcc tcc aac288Met Ala Ala Pro Arg Gly Asn Val Thr Ser Leu Ser Leu Ser Ser Asn35 40 45cgc atc cac cac ctc cat gat tct gac ttt gcc cac ctg ccc agc ctg336Arg Ile His His Leu His Asp Ser Asp Phe Ala His Leu Pro Ser Leu50 55 60cgg cat ctc aac ctc aag tgg aac tgc ccg ccg gtt ggc ctc agc ccc384Arg His Leu Asn Leu Lys Trp Asn Cys Pro Pro Val Gly Leu Ser Pro65 70 75 80atg cac ttc ccc tgc cac atg acc atc gag ccc agc acc ttc ttg gct432Met His Phe Pro Cys His Met Thr Ile Glu Pro Ser Thr Phe Leu Ala85 90 95gtg ccc acc ctg gaa gag cta aac ctg agc tac aac aac atc atg act480Val Pro Thr Leu Glu Glu Leu Asn Leu Ser Tyr Asn Asn Ile Met Thr
100 105 110gtg cct gcg ctg ccc aaa tcc ctc ata tcc ctg tcc ctc agc cat acc528Val Pro Ala Leu Pro Lys Ser Leu Ile Ser Leu Ser Leu Ser His Thr115 120 125aac atc ctg atg cta gac tct gcc agc ctc gcc ggc ctg cat gcc ctg576Asn Ile Leu Met Leu Asp Ser Ala Ser Leu Ala Gly Leu His Ala Leu130 135 140cgc ttc cta ttc atg gac ggc aac tgt tat tac aag aac ccc tgc agg624Arg Phe Leu Phe Met Asp Gly Asn Cys Tyr Tyr Lys Asn Pro Cys Arg145 150 155 160cag gca ctg gag gtg gcc ccg ggt gcc ctc ctt ggc ctg ggc aac ctc672Gln Ala Leu Glu Val Ala Pro Gly Ala Leu Leu Gly Leu Gly Asn Leu165 170 175acc cac ctg tca ctc aag tac aac aac ctc act gtg gtg ccc cgc aac720Thr His Leu Ser Leu Lys Tyr Asn Asn Leu Thr Val Val Pro Arg Asn180 185 190ctg cct tcc agc ctg gag tat ctg ctg ttg tcc tac aac cgc atc gtc768Leu Pro Ser Ser Leu Glu Tyr Leu Leu Leu Ser Tyr Asn Arg Ile Val195 200 205aaa ctg gcg cct gag gac ctg gcc aat ctg acc gcc ctg cgt gtg ctc816Lys Leu Ala Pro Glu Asp Leu Ala Asn Leu Thr Ala Leu Arg Val Leu210 215 220gat gtg ggc gga aat tgc cgc cgc tgc gac cac gct ccc aac ccc tgc864Asp Val Gly Gly Asn Cys Arg Arg Cys Asp His Ala Pro Asn Pro Cys225 230 235 240atg gag tgc cct cgt cac ttc ccc cag cta cat ccc gat acc ttc agc912Met Glu Cys Pro Arg His Phe Pro Gln Leu His Pro Asp Thr Phe Ser245 250 255cac ctg agc cgt ctt gaa ggc ctg gtg ttg aag gac agt tct ctc tcc960His Leu Ser Arg Leu Glu Gly Leu Vat Leu Lys Asp Ser Ser Leu Ser260 265 270tgg ctg aat gcc agt tgg ttc cgt ggg ctg gga aac ctc cga gtg ctg 1008Trp Leu Asn Ala Ser Trp Phe Arg Gly Leu Gly Asn Leu Arg Val Leu275 280 285gac ctg agt gag aac ttc ctc tac aaa tgc atc act aaa acc aag gcc 1056Asp Leu Ser Glu Asn Phe Leu Tyr Lys Cys Ile Thr Lys Thr Lys Ala290 295 300ttc cag ggc cta aca cag ctg cgc aag ctt aac ctg tcc ttc aat tac 1104Phe Gln Gly Leu Thr Gln Leu Arg Lys Leu Asn Leu Ser Phe Asn Tyr305 310 315 320caa aag agg gtg tcc ttt gcc cac ctg tct ctg gcc oct tcc ttc ggg 1152Gln Lys Arg Val Ser Phe Ala His Leu Ser Leu Ala Pro Ser Phe Gly325 330 335
agc ctg gtc gcc ctg aag gag ctg gac atg cac ggc atc ttc ttc cgc1200Ser Leu Val Ala Leu Lys Glu Leu Asp Met His Gly Ile Phe Phe Arg340 345 350tca ctc gat gag acc acg ctc cgg cca ctg gcc cgc ctg ccc atg ctc1248Ser Leu Asp Glu Thr Thr Leu Arg Pro Leu Ala Arg Leu Pro Met Leu355 360 365cag act ctg cgt ctg cag atg aac ttc atc aac cag gcc cag ctc ggc1296Gln Thr Leu Arg Leu Gln Met Asn Phe Ile Asn Gln Ala Gln Leu Gly370 375 380atc ttc agg gcc ttc cct ggc ctg cgc tac gtg gac ctg tcg gac aac1344Ile Phe Arg Ala Phe Pro Gly Leu Arg Tyr Val Asp Leu Ser Asp Asn385 390 395 400cgc atc agc gga gct tcg gag ctg aca gcc acc atg ggg gag gca gat1392Arg Ile Ser Gly Ala Ser Glu Leu Thr Ala Thr Met Gly Glu Ala Asp405 410 415gga ggg gag aag gtc tgg ctg cag cct ggg gac ctt gct ccg gcc cca1440Gly Gly Glu Lys Val Trp Leu Gln Pro Gly Asp Leu Ala Pro Ala Pro420 425 430gtg gac act ccc agc tct gaa gac ttc agg ccc aac tgc agc acc ctc1488Val Asp Thr Pro Ser Ser Glu Asp Phe Arg Pro Asn Cys Ser Thr Leu435 440 445aac ttc acc ttg gat ctg tca cgg aac aac ctg gtg acc gtg cag ccg1536Asn Phe Thr Leu Asp Leu Ser Arg Asn Asn Leu Val Thr Val Gln Pro450 455 460gag atg ttt gcc cag ctc tcg cac ctg cag tgc ctg cgc ctg agc cac1584Glu Met Phe Ala Gln Leu Ser His Leu Gln Cys Leu Arg Leu Ser His465 470 475 480aac tgc atc tcg cag gca gtc aat ggc tcc cag ttc ctg ccg ctg acc1632Asn Cys Ile Ser Gln Ala Val Asn Gly Ser Gln Phe Leu Pro Leu Thr485 490 495ggt ctg cag gtg cta gac ctg tcc cac aat aag ctg gac ctc tac cac1680Gly Leu Gln Val Leu Asp Leu Ser His Asn Lys Leu Asp Leu Tyr His500 505 510gag cac tca ttc acg gag cta cca cga ctg gag gcc ctg gac ctc agc1728Glu His Ser Phe Thr Glu Leu Pro Arg Leu Glu Ala Leu Asp Leu Ser515 520 525tac aac agc cag ccc ttt ggc atg cag ggc gtg ggc cac aac ttc agc1776Tyr Asn Ser Gln Pro Phe Gly Met Gln Gly Val Gly His Asn Phe Ser530 535 540ttc gtg gct cac ctg cgc acc ctg cgc cac ctc agc ctg gcc cac aac1824Phe Val Ala His Leu Arg Thr Leu Arg His Leu Ser Leu Ala His Asn545 550 555 560
aac atc cac agc caa gtg tcc cag cag ctc tgc agt acg tcg ctg cgg1872Asn Ile His Ser Gln Val Ser Gln Gln Leu Cys Ser Thr Ser Leu Arg565 570 575gcc ctg gac ttc agc ggc aat gca ctg ggc cat atg tgg gcc gag gga1920Ala Leu Asp Phe Ser Gly Asn Ala Leu Gly His Met Trp Ala Glu Gly580 585 590gac ctc tat ctg cac ttc ttc caa ggc ctg agc ggt ttg atc tgg ctg1968Asp Leu Tyr Leu His Phe Phe Gln Gly Leu Ser Gly Leu Ile Trp Leu595 600 605gac ttg tcc cag aac cgc ctg cac acc ctc ctg ccc caa acc ctg cgc2016Asp Leu Ser Gln Asn Arg Leu His Thr Leu Leu Pro Gln Thr Leu Arg610 615 620aac ctc ccc aag agc cta cag gtg ctg cgt ctc cgt gac aat tac ctg2064Asn Leu Pro Lys Ser Leu Gln Val Leu Arg Leu Arg Asp Asn Tyr Leu625 630 635 640gcc ttc ttt aag tgg tgg agc ctc cac ttc ctg ccc aaa ctg gaa gtc2112Ala Phe Phe Lys Trp Trp Ser Leu His Phe Leu Pro Lys Leu Glu Val645 650 655ctc gac ctg gca gga aac cag ctg aag gcc ctg acc aat ggc agc ctg2160Leu Asp Leu Ala Gly Asn Gln Leu Lys Ala Leu Thr Asn Gly Ser Leu660 665 670cct gct ggc acc cgg ctc cgg agg ctg gat gtc agc tgc aac agc atc2208Pro Ala Gly Thr Arg Leu Arg Arg Leu Asp Val Ser Cys Asn Ser Ile675 680 685agc ttc gtg gcc ccc ggc ttc ttt tcc aag gcc aag gag ctg cga gag2256Ser Phe Val Ala Pro Gly Phe Phe Ser Lys Ala Lys Glu Leu Arg Glu690 695 700ctc aac ctt agc gcc aac gcc ctc aag aca gtg gac cac tcc tgg ttt2304Leu Asn Leu Ser Ala Asn Ala Leu Lys Thr Val Asp His Ser Trp Phe705 710 715 720ggg ccc ctg gcg agt gcc ctg caa ata cta gat gta agc gcc aac cct2352Gly Pro Leu Ala Ser Ala Leu Gln Ile Leu Asp Val Ser Ala Asn Pro725 730 735ctg cac tgc gcc tgt ggg gcg gcc ttt atg gac ttc ctg ctg gag gtg2400Leu His Cys Ala Cys Gly Ala Ala Phe Met Asp Phe Leu Leu Glu Val740 745 750cag gct gcc gtg ccc ggt ctg ccc agc cgg gtg aag tgt ggc agt ccg2448Gln Ala Ala Val Pro Gly Leu Pro Ser Arg Val Lys Cys Gly Ser Pro755 760 765ggc cag ctc cag ggc ctc agc atc ttt gca cag gac ctg cgc ctc tgc2496Gly Gln Leu Gln Gly Leu Ser Ile Phe Ala Gln Asp Leu Arg Leu Cys770 775 780ctg gat gag gcc ctc tcc tgg gac tgt ttc gcc ctc tcg ctg ctg gct2544
Leu Asp Glu Ala Leu Ser Trp Asp Cys Phe Ala Leu Ser Leu Leu Ala785 790 795 800gtg gct ctg ggc ctg ggt gtg ccc atg ctg cat cac ctc tgt ggc tgg2592Val Ala Leu Gly Leu Gly Val Pro Met Leu His His Leu Cys Gly Trp805 810 815gac ctc tgg tac tgc ttc cac ctg tgc ctg gcc tgg ctt ccc tgg cgg2640Asp Leu Trp Tyr Cys Phe His Leu Cys Leu Ala Trp Leu Pro Trp Arg820 825 830ggg cgg caa agt ggg cga gat gag gat gcc ctg ccc tac gat gcc ttc2688Gly Arg Gln Ser Gly Arg Asp Glu Asp Ala Leu Pro Tyr Asp Ala Phe835 840 845gtg gtc ttc gac aaa acg cag agc gca gtg gca gac tgg gtg tac aac2736Val Val Phe Asp Lys Thr Gln Ser Ala Val Ala Asp Trp Val Tyr Asn850 855 860gag ctt cgg ggg cag ctg gag gag tgc cgt ggg cgc tgg gca ctc cgc2784Glu Leu Arg Gly Gln Leu Glu Glu Cys Arg Gly Arg Trp Ala Leu Arg865 870 875 880ctg tgc ctg gag gaa cgc gac tgg ctg cct ggc aaa acc ctc ttt gag2832Leu Cys Leu Glu Glu Arg Asp Trp Leu Pro Gly Lys Thr Leu Phe Glu885 890 895aac ctg tgg gcc tcg gtc tat ggc agc cgc aag acg ctg ttt gtg ctg2880Asn Leu Trp Ala Ser Val Tyr Gly Ser Arg Lys Thr Leu Phe Val Leu900 905 910gcc cac acg gac cgg gtc agt ggt ctc ttg cgc gcc agc ttc ctg ctg2928Ala His Thr Asp Arg Val Ser Gly Leu Leu Arg Ala Ser Phe Leu Leu915 920 925gcc cag cag cgc ctg ctg gag gac cgc aag gac gtc gtg gtg ctg gtg2976Ala Gln Gln Arg Leu Leu Glu Asp Arg Lys Asp Val Val Val Leu Val930 935 940atc ctg agc cct gac ggc cgc cgc tcc cgc tat gtg cgg ctg cgc cag3024Ile Leu Ser Pro Asp Gly Arg Arg Ser Arg Tyr Val Arg Leu Arg Gln945 950 955 960cgc ctc tgc cgc cag agt gtc ctc ctc tgg ccc cac cag ccc agt ggt3072Arg Leu Cys Arg Gln Ser Val Leu Leu Trp Pro His Gln Pro Ser Gly965 970 975cag cgc agc ttc tgg gcc cag ctg ggc atg gcc ctg acc agg gac aac3120Gln Arg Ser Phe Trp Ala Gln Leu Gly Met Ala Leu Thr Arg Asp Asn980 985 990cac cac ttc tat aac cgg aac ttc tgc cag gga ccc acg gcc gaa tag3168His His Phe Tyr Asn Arg Asn Phe Cys Gln Gly Pro Thr Ala Glu99510001005<210>43
<211>1055<212>PRT<213>未知<400>43Met Pro Met Lys Trp Ser Gly Trp Arg Trp Ser Trp Gly Pro Ala Thr-45 -40 -35His Thr Ala Leu Pro Pro Pro Gln Gly Phe Cys Arg Ser Ala Leu His-30 -25 -20Pro Leu Ser Leu Leu Val Gln Ala Ile Met Leu Ala Met Thr Leu Ala-15 -10 -5 -1Leu Gly Thr Leu Pro Ala Phe Leu Pro Cys Glu Leu Gln Pro His Gly1 5 10 15Leu Val Asn Cys Asn Trp Leu Phe Leu Lys Ser Val Pro His Phe Ser20 25 30Met Ala Ala Pro Arg Gly Asn Val Thr Ser Leu Ser Leu Ser Ser Asn35 40 45Arg Ile His His Leu His Asp Ser Asp Phe Ala His Leu Pro Ser Leu50 55 60Arg His Leu Asn Leu Lys Trp Asn Cys Pro Pro Val Gly Leu Ser Pro65 70 75 80Met His Phe Pro Cys His Met Thr Ile Glu Pro Ser Thr Phe Leu Ala85 90 95Val Pro Thr Leu Glu Glu Leu Asn Leu Ser Tyr Asn Asn Ile Met Thr100 105 110Val Pro Ala Leu Pro Lys Ser Leu Ile Ser Leu Ser Leu Ser His Thr115 120 125Asn Ile Leu Met Leu Asp Ser Ala Ser Leu Ala Gly Leu His Ala Leu130 135 140Arg Phe Leu Phe Met Asp Gly Asn Cys Tyr Tyr Lys Asn Pro Cys Arg145 150 155 160Gln Ala Leu Glu Val Ala Pro Gly Ala Leu Leu Gly Leu Gly Asn Leu165 170 175Thr His Leu Ser Leu Lys Tyr Asn Asn Leu Thr Val Val Pro Arg Asn180 185 190Leu Pro Ser Ser Leu Glu Tyr Leu Leu Leu Ser Tyr Asn Arg Ile Val195 200 205Lys Leu Ala Pro Glu Asp Leu Ala Asn Leu Thr Ala Leu Arg Val Leu210 215 220Asp Val Gly Gly Asn Cys Arg Arg Cys Asp His Ala Pro Asn Pro Cys
225 230 235 240Met Glu Cys Pro Arg His Phe Pro Gln Leu His Pro Asp Thr Phe Ser245 250 255His Leu Ser Arg Leu Glu Gly Leu Val Leu Lys Asp Ser Ser Leu Ser260 265 270Trp Leu Asn Ala Ser Trp Phe Arg Gly Leu Gly Asn Leu Arg Val Leu275 280 285Asp Leu Ser Glu Asn Phe Leu Tyr Lys Cys Ila Thr Lys Thr Lys Ala290 295 300Phe Gln Gly Leu Thr Gln Leu Arg Lys Leu Asn Leu Ser Phe Asn Tyr305 310 315 320Gln Lys Arg Val Ser Phe Ala His Leu Ser Leu Ala Pro Ser Phe Gly325 330 335Ser Leu Val Ala Leu Lys Glu Leu Asp Met His Gly Ile Phe Phe Arg340 345 350Ser Leu Asp Glu Thr Thr Leu Arg Pro Leu Ala Arg Leu Pro Met Leu355 360 365Gln Thr Leu Arg Leu Gln Met Asn Phe Ile Asn Gln Ala Gln Leu Gly370 375 380Ile Phe Arg Ala Phe Pro Gly Leu Arg Tyr Val Asp Leu Ser Asp Asn385 390 395 400Arg Ile Ser Gly Ala Ser Glu Leu Thr Ala Thr Met Gly Glu Ala Asp405 410 415Gly Gly Glu Lys Val Trp Leu Gln Pro Gly Asp Leu Ala Pro Ala Pro420 425 430Val Asp Thr Pro Ser Ser Glu Asp Phe Arg Pro Asn Cys Ser Thr Leu435 440 445Asn Phe Thr Leu Asp Leu Ser Arg Asn Asn Leu Val Thr Val Gln Pro450 455 460Glu Met Phe Ala Gln Leu Ser His Leu Gln Cys Leu Arg Leu Ser His465 470 475 480Asn Cys Ile Ser Gln Ala Val Asn Gly Ser Gln Phe Leu Pro Leu Thr485 490 495Gly Leu Gln Val Leu Asp Leu Ser His Asn Lys Leu Asp Leu Tyr His500 505 510Glu His Ser Phe Thr Glu Leu Pro Arg Leu Glu Ala Leu Asp Leu Ser515 520 525Tyr Asn Ser Gln Pro Phe Gly Met Gln Gly Val Gly His Asn Phe Ser
530535 540Phe Val Ala His Leu Arg Thr Leu Arg His Leu Ser Leu Ala His Asn545 550 555 560Asn Ile His Ser Gln Val Ser Gln Gln Leu Cys Ser Thr Ser Leu Arg565 570 575Ala Leu Asp Phe Ser Gly Asn Ala Leu Gly His Met Trp Ala Glu Gly580 585 590Asp Leu Tyr Leu His Phe Phe Gln Gly Leu Ser Gly Leu Ile Trp Leu595 600 605Asp Leu Ser Gln Asn Arg Leu His Thr Leu Leu Pro Gln Thr Leu Arg610 615 620Asn Leu Pro Lys Ser Leu Gln Val Leu Arg Leu Arg Asp Asn Tyr Leu625 630 635 640Ala Phe Phe Lys Trp Trp Ser Leu His Phe Leu Pro Lys Leu Glu Val645 650 655Leu Asp Leu Ala Gly Asn Gln Leu Lys Ala Leu Thr Asn Gly Ser Leu660 665 670Pro Ala Gly Thr Arg Leu Arg Arg Leu Asp Val Ser Cys Asn Ser Ile675 680 685Ser Phe Val Ala Pro Gly Phe Phe Ser Lys Ala Lys Glu Leu Arg Glu690 695 700Leu Asn Leu Ser Ala Asn Ala Leu Lys Thr Val Asp His Ser Trp Phe705 710 715 720Gly Pro Leu Ala Ser Ala Leu Gln Ile Leu Asp Val Ser Ala Asn Pro725 730 735Leu His Cys Ala Cys Gly Ala Ala Phe Met Asp Phe Leu Leu Glu Val740 745 750Gln Ala Ala Val Pro Gly Leu Pro Ser Arg Val Lys Cys Gly Ser Pro755 760 765Gly Gln Leu Gln Gly Leu Ser Ile Phe Ala Gln Asp Leu Arg Leu Cys770 775 780Leu Asp Glu Ala Leu Ser Trp Asp Cys Phe Ala Leu Ser Leu Leu Ala785 790 795 800Val Ala Leu Gly Leu Gly Val Pro Met Leu His His Leu Cys Gly Trp805 810 815Asp Leu Trp Tyr Cys Phe His Leu Cys Leu Ala Trp Leu Pro Trp Arg820 825 830Gly Arg Gln ser Gly Arg Asp Glu Asp Ala Leu Pro Tyr Asp Ala Phe
835 840 845Val Val Phe Asp Lys Thr Gln Ser Ala Val Ala Asp Trp Val Tyr Asn850 855 860Glu Leu Arg Gly Gln Leu Glu Glu Cys Arg Gly Arg Trp Ala Leu Arg865 870 875 880Leu Cys Leu Glu Glu Arg Asp Trp Leu Pro Gly Lys Thr Leu Phe Glu885 890 895Asn Leu Trp Ala Ser Val Tyr Gly Ser Arg Lys Thr Leu Phe Val Leu900 905 910Ala His Thr Asp Arg Val Ser Gly Leu Leu Arg Ala Ser Phe Leu Leu915 920 925Ala Gln Gln Arg Leu Leu Glu Asp Arg Lys Asp Val Val Val Leu Val930 935 940Ile Leu Ser Pro Asp Gly Arg Arg Ser Arg Tyr Val Arg Leu Arg Gln945 950 955 960Arg Leu Cys Arg Gln Ser Val Leu Leu Trp Pro His Gln Pro Ser Gly965 970 975Gln Arg Ser Phe Trp Ala Gln Leu Gly Met Ala Leu Thr Arg Asp Asn980 985 990His His Phe Tyr Asn Arg Asn Phe Cys Gln Gly Pro Thr Ala Glu99510001005<210>44<211>2289<212>DNA<213>未知<220>
<223>未知生物的说明啮齿类动物；推测为小鼠(Mus musculus)<220>
<221>CDS<222>(1)..(2079)<400>44aac ctg tcc ttc aat tac cgc aag aag gta tcc ttt gcc cgc ctc cac 48Asn Leu Ser Phe Asn Tyr Arg Lys Lys Val Ser Phe Ala Arg Leu His1 5 l0 15ctg gca agt tcc ttt aag aac ctg gtg tca ctg cag gag ctg aac atg 96Leu Ala Ser Ser Phe Lys Asn Leu Val Ser Leu Gln Glu Leu Asn Met20 25 30aac ggc atc ttc ttc cgc ttg ctc aac aag tac acg ctc aga tgg ctg144
Asn Gly Ile Phe Phe Arg Leu Leu Asn Lys Tyr Thr Leu Arg Trp Leu35 40 45gcc gat ctg ccc aaa ctc cac act ctg cat ctt caa atg aac ttc atc192Ala Asp Leu Pro Lys Leu His Thr Leu His Leu Gln Met Asn Phe Ile50 55 60aac cag gca cag ctc agc atc ttt ggt acc ttc cga gcc ctt cgc ttt240Asn Gln Ala Gln Leu Ser Ile Phe Gly Thr Phe Arg Ala Leu Arg Phe65 70 75 80gtg gac ttg tca gac aat cgc atc agt ggg cct tca acg ctg tca gaa288Val Asp Leu Ser Asp Asn Arg Ile Ser Gly Pro Ser Thr Leu Ser Glu85 90 95gcc acc cct gaa gag gca gat gat gca gag cag gag gag ctg ttg tct336Ala Thr Pro Glu Glu Ala Asp Asp Ala Glu Gln Glu Glu Leu Leu Ser100 105 110gcg gat cct cac cca gct ccg ctg agc acc cct gct tct aag aac ttc384Ala Asp Pro His Pro Ala Pro Leu Ser Thr Pro Ala Ser Lys Asn Phe115 120 125atg gac agg tgt aag aac ttc aag ttc aac atg gac ctg tct cgg aac432Met Asp Arg Cys Lys Asn Phe Lys Phe Asn Met Asp Leu Ser Arg Asn130 135 140aac ctg gtg act atc aca gca gag atg ttt gta aat ctc tca cgc ctc480Asn Leu Val Thr Ile Thr Ala Glu Met Phe Val Asn Leu Ser Arg Leu145 150 155 160cag tgt ctt agc ctg agc cac aac tca att gca cag gct gtc aat ggc528Gln Cys Leu Ser Leu Ser His Asn Ser Ile Ala Gln Ala Val Asn Gly165 170 175tct cag ttc ctg ccg ctg acc ggt ctg cag gtg cta gac ctg tcc cac576Ser Gln Phe Leu Pro Leu Thr Gly Leu Gln Val Leu Asp Leu Ser His180 185 190aat aag ctg gac ctc tac cac gag cac tca ttc acg gag cta cca cga624Asn Lys Leu Asp Leu Tyr His Glu His Ser Phe Thr Glu Leu Pro Arg195 200 205ctg gag gcc ctg gac ctc agc tac aac agc cag ccc ttt agc atg aag672Leu Glu Ala Leu Asp Leu Ser Tyr Asn Ser Gln Pro Phe Ser Met Lys210 215 220ggt ata ggc cac aat ttc agt ttt gtg acc cat ctg tcc atg cta cag720Gly Ile Gly His Asn Phe Ser Phe Val Thr His Leu Ser Met Leu Gln225 230 235 240agc ctt agc ctg gca cac aat gac att cat acc cgt gtg tcc tca cat768Ser Leu Ser Leu Ala His Asn Asp Ile His Thr Arg Val Ser Ser His245 250 255ctc aac agc aac tca gtg agg ttt ctt gac ttc agc ggc aac ggt atg816Leu Asn Ser Asn Ser Val Arg Phe Leu Asp Phe Ser Gly Asn Gly Met
260 265 270ggc cgc atg tgg gat gag ggg ggc ctt tat ctc cat ttc ttc caa ggc864Gly Arg Met Trp Asp Glu Gly Gly Leu Tyr Leu His Phe Phe Gln Gly275 280 285ctg agt ggc gtg ctg aag ctg gac ctg tct caa aat aac ctg cat atc912Leu Ser Gly Val Leu Lys Leu Asp Leu Ser Gln Asn Asn Leu His Ile290 295 300ctc cgg ccc cag aac ctt gac aac ctc ccc aag agc ctg aag ctg ctg960Leu Arg Pro Gln Asn Leu Asp Asn Leu Pro Lys Ser Leu Lys Leu Leu305 310 315 320agc ctc cga gac aac tac cta tct ttc ttt aac tgg acc agt ctg tcc 1008Ser Leu Arg Asp Asn Tyr Leu Ser Phe Phe Asn Trp Thr Ser Leu Ser325 330 335ttc cta ccc aac ctg gaa gtc cta gac ctg gca ggc aac cag cta aag 1056Phe Leu Pro Asn Leu Glu Val Leu Asp Leu Ala Gly Asn Gln Leu Lys340 345 350gcc ctg acc aat ggc acc ctg cct aat ggc acc ctc ctc cag aaa ctc 1104Ala Leu Thr Asn Gly Thr Leu Pro Asn Gly Thr Leu Leu Gln Lys Leu355 360 365gat gtc agt agc aac agt atc gtc tct gtg gcc ccc ggc ttc ttt tcc 1152Asp Val Ser Ser Asn Ser Ile Val Ser Val Ala Pro Gly Phe Phe Ser370 375 380aag gcc aag gag ctg cga gag ctc aac ctt agc gcc aac gcc ctc aag 1200Lys Ala Lys Glu Leu Arg Glu Leu Asn Leu Ser Ala Asn Ala Leu Lys385 390 395 400aca gtg gac cac tcc tgg ttt ggg ccc att gtg atg aac ctg aca gtt 1248Thr Val Asp His Ser Trp Phe Gly Pro Ile Val Met Asn Leu Thr Val405 410 415cta gac gtg aga agc aac cct ctg cac tgt gcc tgt ggg gca gcc ttc 1296Leu Asp Val Arg Ser Asn Pro Leu His Cys Ala Cys Gly Ala Ala Phe420 425 430gta gac tta ctg ttg gag gtg cag acc aag gtg cct ggc ctg gct aat 1344Val Asp Leu Leu Leu Glu Val Gln Thr Lys Val Pro Gly Leu Ala Asn435 440 445ggt gtg aag tgt ggc agc ccc ggc cag ctg cag ggc cgt agc atc ttc 1392Gly Val Lys Cys Gly Ser Pro Gly Gln Leu Gln Gly Arg Ser Ile Phe450 455 460gcg cag gac ctg cgg ctg tgc ctg gat gag gtc ctc tct tgg gac tgc 1440Ala Gln Asp Leu Arg Leu Cys Leu Asp Glu Val Leu Ser Trp Asp Cys465 470 475 480ttt ggc ctt tca ctc ttg gct gtg gcc gtg ggc atg gtg gtg cct ata 1488Phe Gly Leu Ser Leu Leu Ala Val Ala Val Gly Met Val Val Pro Ile485 490 495
ctg cac cat ctc tgc ggc tgg gac gtc tgg tac tgt ttt cat ctg tgc1536Leu His His Leu Cys Gly Trp Asp Val Trp Tyr Cys Phe His Leu Cys500 505 510ctg gca tgg cta cct ttg cta gcc cgc agc cga cgc agc gcc caa act1584Leu Ala Trp Leu Pro Leu Leu Ala Arg Ser Arg Arg Ser Ala Gln Thr515 520 525ctc cct tat gat gcc ttc gtg gtg ttc gat aag gca cag agc gca gtt1632Leu Pro Tyr Asp Ala Phe Val Val Phe Asp Lys Ala Gln Ser Ala Val530 535 540gcc gac tgg gtg tat aac gag ctg cgg gtg cgg ctg gag gag cgg cgc1680Ala Asp Trp Val Tyr Asn Glu Leu Arg Val Arg Leu Glu Glu Arg Arg545 550 555 560ggc cgc tgg gca ctc cgc ctg tgc ctg gag gac cga gat tgg ctg cct1728Gly Arg Trp Ala Leu Arg Leu Cys Leu Glu Asp Arg Asp Trp Leu Pro565 570 575ggc cag acg ctc ttc gag aac ctc tgg gct tcc atc tat ggg agc cgc1776Gly Gln Thr Leu Phe Glu Asn Leu Trp Ala Ser Ile Tyr Gly Ser Arg580 585 590aag act cta ttt gtg ctg gcc cac acg gac cgc gtc agt ggc ctc ctg1824Lys Thr Leu Phe Val Leu Ala His Thr Asp Arg Val Ser Gly Leu Leu595 600 605cgc acc agc ttc ctg ctg gct cag cag cgc ctg ttg gaa gac cgc aag1872Arg Thr Ser Phe Leu Leu Ala Gln Gln Arg Leu Leu Glu Asp Arg Lys610 615 620gac gtg gtg gtg ttg gtg atc ctg cgt ccg gat gcc cac cgc tcc cgc1920Asp Val Val Val Leu Val Ile Leu Arg Pro Asp Ala His Arg Ser Arg625 630 635 640tat gtg cga ctg cgc cag cgt ctc tgc cgc cag agt gtg ctc ttc tgg1968Tyr Val Arg Leu Arg Gln Arg Leu Cys Arg Gln Ser Val Leu Phe Trp645 650 655ccc cag cag ccc aac ggg cag ggg ggc ttc tgg gcc cag ctg agt aca2016Pro Gln Gln Pro Asn Gly Gln Gly Gly Phe Trp Ala Gln Leu Ser Thr660 665 670gcc ctg act agg gac aac cgc cac ttc tat aac cag aac ttc tgc cgg2064Ala Leu Thr Arg Asp Asn Arg His Phe Tyr Asn Gln Asn Phe Cys Arg675 680 685gga cct aca gca gaa tagctcagag caacagctgg aaacagctgc atcttcatgt2119Gly Pro Thr Ala Glu690ctggttcccg agttgctctg cctgccttgc tctgtcttac tacaccgcta tttggcaagt 2179gcgcaatata tgctaccaag ccaccaggcc cacggagcaa aggttggctg taaagggtag 2239
ttttcttccc atgcatcttt caggagagtg aagatagaca ccaaacccac2289<210>45<211>693<212>PRT<213>未知<400>45Asn Leu Ser Phe Asn Tyr Arg Lys Lys Val Ser Phe Ala Arg Leu His1 5 10 15Leu Ala Ser Ser Phe Lys Asn Leu Val Ser Leu Gln Glu Leu Asn Met20 25 30Asn Gly Ile Phe Phe Arg Leu Leu Asn Lys Tyr Thr Leu Arg Trp Leu35 40 45Ala Asp Leu Pro Lys Leu His Thr Leu His Leu Gln Met Asn Phe Ile50 55 60Asn Gln Ala Gln Leu Ser Ile Phe Gly Thr Phe Arg Ala Leu Arg Phe65 70 75 80Val Asp Leu Ser Asp Asn Arg Ile Ser Gly Pro Ser Thr Leu Ser Glu85 90 95Ala Thr Pro Glu Glu Ala Asp Asp Ala Glu Gln Glu Glu Leu Leu Ser100 105 110Ala Asp Pro His Pro Ala Pro Leu Ser Thr Pro Ala Ser Lys Asn Phe115 120 125Met Asp Arg Cys Lys Asn Phe Lys Phe Asn Mer Asp Leu Ser Arg Asn130 135 140Asn Leu Val Thr Ile Thr Ala Glu Met Phe Val Asn Leu Ser Arg Leu145 150 155 160Gln Cys Leu Ser Leu Ser His Asn Ser Ile Ala Gln Ala Val Asn Gly165 170 175Ser Gln Phe Leu Pro Leu Thr Gly Leu Gln Val Leu Asp Leu Ser His180 185 190Asn Lys Leu Asp Leu Tyr His Glu His Ser Phe Thr Glu Leu Pro Arg195 200 205Leu Glu Ala Leu Asp Leu Ser Tyr Asn Ser Gln Pro Phe Ser Met Lys210 215 220Gly Ile Gly His Asn Phe Ser Phe Val Thr His Leu Ser Met Leu Gln225 230 235 240Ser Leu Ser Leu Ala His Asn Asp Ile His Thr Arg Val Ser Ser His245 250 255
Leu Asn Ser Asn Ser Val Arg Phe Leu Asp Phe Ser Gly Asn Gly Met260 265 270Gly Arg Met Trp Asp Glu Gly Gly Leu Tyr Leu His Phe Phe Gln Gly275 280 285Leu Ser Gly Val Leu Lys Leu Asp Leu Ser Gln Asn Asn Leu His Ile290 295 300Leu Arg Pro Gln Asn Leu Asp Asn Leu Pro Lys Ser Leu Lys Leu Leu305 310 315 320Ser Leu Arg Asp Asn Tyr Leu Ser Phe Phe Asn Trp Thr Ser Leu Ser325 330 335Phe Leu Pro Asn Leu Glu Val Leu Asp Leu Ala Gly Asn Gln Leu Lys340 345 350Ala Leu Thr Asn Gly Thr Leu Pro Asn Gly Thr Leu Leu Gln Lys Leu355 360 365Asp Val Ser Ser Asn Ser Ile Val Ser Val Ala Pro Gly Phe Phe Ser370 375 380Lys Ala Lys Glu Leu Arg Glu Leu Asn Leu Ser Ala Asn Ala Leu Lys385 390 395 400Thr Val Asp His Ser Trp Phe Gly Pro Ile Val Met Asn Leu Thr Val405 410 415Leu Asp Val Arg Ser Asn Pro Leu His Cys Ala Cys Gly Ala Ala Phe420 425 430Val Asp Leu Leu Leu Glu Val Gln Thr Lys Val Pro Gly Leu Ala Asn435 440 445Gly Val Lys Cys Gly Ser Pro Gly Gln Leu Gln Gly Arg Ser Ile Phe450 455 460Ala Gln Asp Leu Arg Leu Cys Leu Asp Glu Val Leu Ser Trp Asp Cys465 470 475 480Phe Gly Leu Ser Leu Leu Ala Val Ala Val Gly Met Val Val Pro Ile485 490 495Leu His His Leu Cys Gly Trp Asp Val Trp Tyr Cys Phe His Leu Cys500 505 510Leu Ala Trp Leu Pro Leu Leu Ala Arg Ser Arg Arg Ser Ala Gln Thr515 520 525Leu Pro Tyr Asp Ala Phe Val Val Phe Asp Lys Ala Gln Ser Ala Val530 535 540Ala Asp Trp Val Tyr Asn Glu Leu Arg Val Arg Leu Glu Glu Arg Arg545 550 555 560
Gly Arg Trp Ala Leu Arg Leu Cys Leu Glu Asp Arg Asp Trp Leu Pro565 570 575Gly Gln Thr Leu Phe Glu Asn Leu Trp Ala Ser Ile Tyr Gly Ser Arg580 585 590Lys Thr Leu Phe Val Leu Ala His Thr Asp Arg Val Ser Gly Leu Leu595 600 605Arg Thr Ser Phe Leu Leu Ala Gln Gln Arg Leu Leu Glu Asp Arg Lys610 615 620Asp Val Val Val Leu Val Ile Leu Arg Pro Asp Ala His Arg Ser Arg625 630 635 640Tyr Val Arg Leu Arg Gln Arg Leu Cys Arg Gln Ser Val Leu Phe Trp645 650 655Pro Gln Gln Pro Asn Gly Gln Gly Gly Phe Trp Ala Gln Leu Ser Thr660 665 670Ala Leu Thr Arg Asp Asn Arg His Phe Tyr Asn Gln Asn Phe Cys Arg675 680 685Gly Pro Thr Ala Glu690
权利要求
1.一种抗原性多肽，其包含SEQ ID NO41的至少20个连续氨基酸残基。
2.一种抗原性多肽，其包含SEQ ID NO41的氨基酸残基1-765。
3.一种抗原性多肽，其包含SEQ ID NO41。
4.一种抗原性多肽，其为SEQ ID NO41。
5.一种融合蛋白，其包含权利要求1-4中任一项的多肽。
6.一种抗体或抗体片段，其特异性地与权利要求1-4中任一项的多肽结合。
7.一种核酸，其编码权利要求1-4中任一项的多肽。
8.一种表达载体，其包含权利要求7的核酸。
9.一种宿主细胞，其包含权利要求8的载体。
10.一种重组生产权利要求1-4中任一项的多肽的方法，其包括在表达多肽的条件下培养权利要求9的宿主细胞。
全文摘要
编码人受体等哺乳动物受体的核酸、纯化受体蛋白，及其片段。此外还提供抗体，包括多克隆抗体和单克隆抗体。本发明还提供将这些组合物应用于诊断和治疗的方法。
文档编号C07K16/28GK1721443SQ20051008859
公开日2006年1月18日 申请日期2001年5月23日 优先权日2000年5月25日
发明者G·T·哈迪曼, F·L·罗克, J·F·巴赞, R·A·卡斯特莱恩, S·W·K·侯, Y·－J·刘 申请人:先灵公司