CN101142482A - 蛋白错误折叠和聚集的调节因子及其使用方法 - Google Patents
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Abstract
本发明提供多核苷酸分子、该分子所编码的蛋白，以及诊断和治疗以蛋白聚集为特征的神经失调的方法。在此所描述的基因影响到聚集倾向蛋白(如α－突触核蛋白)的错误折叠和其后的聚集，并且该基因涉及与蛋白聚集相关神经疾病的诊断和治疗，如帕金森综合症。用RNAi击倒在本文描述本文所述的基因的表达导致α－突触核蛋白在蛋白聚集的C.elegans(C.elegans)模型中的聚集。可以通过过表达蛋白来提供在神经毒素6－OHDA暴露或α－突触核蛋白过表达后的多巴胺能神经保护。对蛋白错误折叠和聚集相关基因的了解提供了开发诊断筛选方法、突变分析和用于开发治疗神经退行性疾病如帕金森综合症的新型治疗和神经保护化合物的药物设计信息的有力手段。
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相关申请的交叉引用
本申请要求美国临时专利申请于2005年2月25日提交的60/656,334，2005年11月21提交的60/738,761和2005年12月12日提交的60/749,910的优先权，其通过在此的引用的方式而被纳入本文。
技术领域
本发明涉及编码调节蛋白聚集的神经保护蛋白的多核苷酸分子及其使用方法。更具体的，本发明涉及使用多核苷酸分子及其编码的神经保护蛋白阻止蛋白错误折叠和多巴胺能神经元变性的方法。
背景技术
神经元功能障碍和损伤可以由毒性的、聚集倾向的蛋白造成并且一些神经失调以此情况为特征。所包括的失调诸如肌萎缩性侧索硬化症、阿耳茨海默氏病、帕金森氏病病、朊病毒病毒病、多谷氨酰胺扩增病(polygultamine expansiondisease)、脊髓-小脑共济失调、脊髓性和延髓性肌肉萎缩、海绵状脑病、tau蛋白病、亨廷顿舞蹈病或者肌张力障碍(dystonia)。编码引起这些失调的毒性、聚集倾向的蛋白和编码这些蛋白的基因已经鉴定出来了。正常的代谢酶类循环蛋白质从而建立了一个永久的合成和降解循环。这些基因的突变导致错误折叠蛋白的非正常积累和降解。已知这些错误折叠的蛋白导致神经元包裹和斑块(neuronal inclusion and plaques)，是神经元损伤的征兆。因此，了解其细胞机制，鉴定减少、抑制和修正这些错误折叠蛋白所需的分子工具是十分重要的。而且，了解蛋白错误折叠和聚集对神经元存活的影响将促进针对这些失调的合理有效治疗的发展。
帕金森氏病是一种神经性失调，其特征为肢体震颤、慢或无运动、僵肢、拖步行走和驼背姿势。其他症状包括抑郁、性格改变、痴呆、睡眠紊乱、语言受损或性功能障碍。这些状况会逐渐加重。这些症状是在基底神经节，尤其是在中缝核群和蓝斑区具有继发退化的黑质区的神经元的退化结果。这种神经元退化通常与α-突触核蛋白的错误折叠及其后的聚集相关。在黑质区的神经元退化导致了神经递质、多巴胺的减少，产生神经递质缺乏，造成多种运动技能的严重损伤。
α-突触核蛋白的突变体被认为会升高错误折叠的倾向，并诱导其他蛋白融合入聚集体。蛋白降解酶的缺失也会促进蛋白积累、聚集和改变细胞内稳态。这些聚集体被称为路易小体，主要由a-突触核蛋白组成。它们形成了帕金森氏病、路易小体痴呆症和其他神经退行性疾病的病理学特征。路易小体与在阿耳茨海默氏病人上发现的β-淀粉样斑块相似。事实上，α-突触核蛋白也是这些阿耳茨海默氏病相关斑块的最大组成成分。帕金森氏病人大脑中路易小体的出现与多巴胺能神经元损失及其后的运动控制的丧失是同步的。α-突触核蛋白在神经元纤维缠结的出现也涉及阿耳茨海默氏病、皮克病、进行性核上性麻痹和皮质基底节变性。
神经退行性失调的一大障碍是直到临床症状表现出之前，患者都不清楚促使神经元退化的神经元环境一直在发展。到临床症状出现时，已经有大量的神经元损失并且神经元环境已经明显不利于神经元存活。缺少可靠的蛋白聚集或神经元损失的早期检测方法使得这些退行性疾病在无监测的状态下发展，直到由于神经元已经损失使得治疗可能无效或多余的地步。而且，即使有可靠的早期检测方法，现有的治疗对这些神经退行性疾病的长期治疗也是无效的，因此需要新药和新的治疗方法。
对异常蛋白聚集的分子机制和蛋白调节因子的了解是开发改进方法所需要的，这些改进方法用于在出现显著神经元破坏前的早期阶段诊断这些失调并为药物设计和开发提供模式系统。使用模式系统，可以筛选并开发靶向特异基因的化合物和与蛋白降解相关的基因产物。有必要了解神经退行性病变的机制并开发神经保护化合物以阻止或缓解神经元损失，直至针对异常蛋白折叠和聚集的根本原因的更有效治疗方法开发出来。
发明概述
本发明是针对使用多核苷酸分子及其编码蛋白的新方法，其用于诊断和治疗以神经元功能障碍、神经退行性病变或蛋白错误折叠及随后聚集为特征的神经性失调的方法。尤其是，在本文描述了一些基因，其可以影响到错误折叠和随后聚集倾向蛋白的聚集，并暗示这些基因可用于与蛋白聚集相关的神经疾病的诊断和治疗。在本文描述的基因会导致蛋白错误折叠和聚集的增加，尤其是这些基因在RNAi筛选中击倒后会提高α-突触核蛋白的错误折叠和聚集。对与此过程相关基因的了解将为开发诊断筛选方法、突变分析和开发全新治疗性和神经保护化合物的药物设计信息提供有力的手段。这些方法包括调节一些蛋白的活性以减少或阻止蛋白错误折叠，或者提供神经保护。这些蛋白包括泛素-蛋白酶体降解系统蛋白、自噬蛋白、分子伴侣、转录因子、膜泡转运蛋白(vesicular trafficking protein)、Mn2+/Fe2+转运子、HSPCI 17蛋白、乙酰胆碱受体亚单位、DJ-I蛋白和PINK-I蛋白。
相应地，本发明的一个目的是提供检测和治疗与蛋白错误折叠和聚集相关的神经失调的方法和化合物。
本发明的另一个目的是提供检测和治疗特别是由α-突触核蛋白错误折叠和聚集造成的帕金森综合症的方法和化合物。
本发明的另一个目的是提供检测某人是否有神经退行性失调的方法，其中失调的特征是与蛋白错误折叠和聚集相关基因的表达水平的改变或者该基因的一个或多个突变。
本发明的另一个目的是提供检测其他神经元基因突变或多态性的方法，这些基因产生特定的表型即在与该基因神经解剖学表达相一致的哺乳动物中引起明显的临床症状。
本发明的另一个目的是提供对人体内蛋白错误折叠和聚集相关神经失调的诊断方法。尤其是，提供一种诊断人体内失调是否存在、预测发展为该失调的可能性或发展为该失调的易感性的方法。
本发明的另一个目的是提供一种鉴定神经元基因突变和多态性的方法，此基因与引起神经元疾病高度易感性的蛋白聚集相关。
本发明的另一个目的是提供一种筛选可减少、抑制、改善或阻止蛋白错误折叠和聚集的化合物的方法，此方法是通过比较化合物存在时蛋白错误折叠和聚集的数量与化合物不存在时蛋白错误折叠和聚集的数量进行的。
本发明的另一个目的是提供一种筛选可减少、抑制、改善或阻止神经退行性病变的化合物的方法，此方法是通过比较化合物存在时神经退行性变的数量与化合物不存在时神经退行性病变的数量进行的。
本发明的另一个目的是提供设计和开发治疗性化合物的方法，该化合物可以是以对促进蛋白聚集环境易感的神经元提供神经保护的化合物，或者阻止或缓解蛋白错误折叠和聚集的化合物，或者溶解蛋白聚集的化合物。
本发明的另一个目的是提供一种减少、停止、减轻、改善或阻止由于蛋白聚集造成的细胞功能紊乱的方法。
本发明的另一个目的是提供含有效量组合物的药物配方，用以在需要治疗或提供神经保护的动物中降低蛋白错误折叠和聚集。
本发明也指使用多核苷酸分子及其编码的多肽为对促进蛋白错误折叠和聚集的环境易感的神经元提供神经保护的方法。
本发明的另一个目的是提供制作用于治疗与蛋白错误折叠和聚集相关的神经疾病的药剂的方法。
本发明的另一个目的是提供用于筛选治疗神经失调新治疗剂的转基因动物。
本发明的另一个目的是提供在于人体内诊断神经退行性失调是否存在的试剂盒，此试剂盒包括一个或多个用于在由人体获得的样品中检测基因突变的试剂。
以下对所公开的具体实施方式的详细描述和所附权利要求书使本发明的这些及其他目的、特点和优点在更清晰。
附图说明
图1a是显示为得到阳性候选基因对α-突触核蛋白::GFP+TOR-2转基因线虫进行筛选的结果概略图。
图1b是显示从初次筛选得到的对α-突触核蛋白::GFP+TOR-2转基因线虫阳性候选基因分布的概略图。
图2a是显示从共表达DJ-I和PINK1的微阵列实验中所鉴定的候选基因重叠的概略图。
图2b是显示表1所列的17个候选基因的概略图。这些基因根据筛选所得的功能分布显示了它们的分类存在显著的重叠。
图3a是显示在动物成长期间暴露于6-OHDA(6-羟基多巴胺)，线虫M7.5蛋白表达对多巴胺神经元的神经保护效果的图表。
图3b是显示对TRO-2和自噬蛋白M7.5对6-OHDA(6-羟基多巴胺)诱导的多巴胺神经元神经退行性病变的神经保护的质量比较的图表。
图4是显示TRO-2和自噬蛋白M7.5对过表达人α-突触核蛋白诱导产生的多巴胺神经元退行性病变的神经保护能力的图表。
发明详细描述
本发明通过参照以下所包括的详细描述的特定实施例可以更容易理解。尽管本发明通过引用一些实施例的具体细节而进行描述，但并不意味着这些细节用于限制本发明的范围。本文提到的参考文献的内容通过整体引用的方式将其纳入本文。
神经元尤其对突变或错误折叠蛋白的毒性功效易感。基于对置于有害的、具有潜在毒性的蛋白中的正常细胞机制的理解，本发明提供了取消错误折叠或聚集蛋白对神经元作用的特殊方法和化合物。突变或错误折叠蛋白可以导致神经元的损伤、退行性病变或死亡，但也可造成神经元的功能紊乱，此时神经元存活但细胞生理过程受损从而导致神经疾病的临床症状的出现。
在本说明书和所附权利要求中，特定的“一”、“一个”和“某个”除非在文中明确说明外，都包括复数形式。
应该知道尽管以下讨论特指人类患者，但所教授内容也可用于任何表达表1中蛋白的动物。在此定义的名词“哺乳动物”是指任何脊椎动物，包括单孔动物和有袋动物。哺乳动物种的例子包括灵长类(如人、猴子、黑猩猩和狒狒)，啮齿类(如大鼠、小鼠、豚鼠和仓鼠)以及反刍动物(如牛和马)。
在本发明范围内的“治疗”包括减少、抑制、改善或阻止与异常相关的症状或分子事件，所述异常例如神经退行性病症，其包括但不局限于帕金森氏病。优选地，可治疗蛋白聚集、由蛋白错误折叠和聚集造成的细胞功能紊乱，和蛋白-聚集-相关疾病。
“神经失调”包括以神经元退化和/或损失为特征的临床状况。这些失调包括肌萎缩性侧索硬化症、阿耳茨海默氏病、帕金森氏病、朊病毒病、额颞叶痴呆、多谷氨酰胺扩增病、spincocerebellar(脊髓-小脑)共济失调、脊髓性和延髓性肌肉萎缩、海绵状脑病、tau蛋白病、亨廷顿舞蹈病、肌张力障碍和类似的病症。
在此所使用的名词“线虫”是指用于研究本发明的蛋白聚集的模式系统，此模式生物来源于线虫动物门。本词义包括特定的线虫动物C.elegans或称为C.elegans。
正确折叠需要蛋白质在一群可能结构中选择一个特定的结构而不是不正确的构型。多肽选择合适结构的失败是对细胞功能和存活力的主要威胁。错误折叠的蛋白可能本身有毒性或者对自身产生毒性，并且产生聚集体从而具有非常严重甚至是致死的结果。因此，进化出精细的系统来保护细胞免受错误折叠蛋白的有害作用。
本发明范围内的“蛋白”包括全长蛋白、同系物、糖基化改变的蛋白、蛋白片段、剪接变异体、功能等同的变异体、基本保留了与野生型蛋白相同的功能的突变体和保守替换蛋白。
本发明范围内的“蛋白聚集”包括至少两个多肽以某种方式彼此相接触从而导致任何一个多肽都处于不溶解的现象。这也包括多肽自然功能或活性的丢失。
本发明范围内的“蛋白-聚集-相关疾病”包括任何疾病、失调和/或痛苦，蛋白-聚集-相关疾病包括神经退行性失调。
对含有实施基本技术的定义、方法和手段的标准分子生物学课本所做的参考包括在本发明内。请见，如Sambrook等，分子克隆：实验室手册，第三版，冷泉港实验室出版社，纽约(2001)，最新分子生物学操作，Ausdbel等(多人)，约翰威立国际出版公司，纽约(2001)以及多种在此引用的参考文献。
本发明提供了多个编码与蛋白错误折叠/聚集和神经保护相关的蛋白的多核苷酸。一些候选基因编码功能或活性至今仍未知的假拟蛋白。然而，本发明确认这些蛋白的至少一个共同功能或活性是阻止蛋白错误折叠和聚集。使用RNAi降低这些蛋白的活性会导致在C.elegans模型中蛋白的错误折叠和α-突触核蛋白的聚集。对这些蛋白及编码它们的多核苷酸的可降低表达和/或活性的改变将导致蛋白错误折叠和聚集。
这些蛋白中的一些也提供对例如含多巴胺神经元等神经元的神经保护。相应地，本发明提供了一种在神经退行性疾病中进行治疗介入的全新方法，其包括使用在本文描述的多核苷酸，以用于对含多巴胺神经元进行神经保护；这样本发明为发展帕金森综合症的治疗提供了另外一条途径。那些编码在多巴胺能神经元内破坏神经保护性能的蛋白的基因可以用来开发基因和蛋白疗法、抗体疗法以及设计和筛选为多巴胺神经元提供神经保护的新药物。相似的，这些分子的改变会使神经元在不利的条件下倾向于受损和死亡。这些基因所编码的蛋白包括UPS组分、自噬机制的组分、分子伴侣、转录因子、膜泡转运蛋白、Mn2+/Fe2+转运子、HSPC117蛋白、乙酰胆碱受体亚单位、DJ-I蛋白和PINK-I蛋白。这些蛋白的列表在表1中提供。
表1：
| C.elegansORF标识 | 预测功能 | 人同源蛋白 | E值 |
| Y37A1B.13(tor-2) | AAA+超家族的ATP酶，路易小体(伴侣)的组分 | Torsin A，负责早发的肌张力障碍 | 2.4e-63 |
| F57B10.5 | 膜运输蛋白(膜泡运输)Emp24/gp25L/p24家族 | CGI-109蛋白 | 2.7e-58 |
| R05D11.6 | 转录因子 | 假拟蛋白MGC13017 | 9.1e-05 |
| F16A11.2 | 未鉴定的保守蛋白(HSPC117蛋白) | 假拟蛋白HSPC117 | 2e-207 |
| F26E4.11 | E3泛素链接酶(UPS蛋白) | 自分泌运动因子受体，异构体2 | 1.9e-39 |
| B0432.2(DJ-I) | 未知功能(DJ-I白) | PD相关蛋白，DJ-I | 1.3e-45 |
| EEED8.9(PINK-1) | BRPK/PTEN诱导的蛋白激酶， | 剪接异构体1；丝氨酸/ | 2.1e-53 |
| PD相关蛋白(PINK-1蛋白) | 苏氨酸激酶PINK1，线粒体前体 | ||
| C35D10.2 | RGS-GAIP相互作用蛋白GIPC(自噬蛋白) | RGS19相互作用蛋白1 | 1.1e-49 |
| F11H8.1(rfl-1) | NEDD8活化复合物，催化组分UBA3(UPS蛋白) | 泛素活化酶E1C | 5.3e-117 |
| T13A10.2 | 预测的E3泛素链接酶(UPS蛋白) | 分成三部分的基序蛋白2 | 0.00012 |
| M7.5 | 泛素活化E1酶样蛋白，(自噬蛋白) | E1样蛋白 | 7.4e-87 |
| T08D2.4 | 具有RING指基序的假拟蛋白(E3链接酶)(UPS蛋白) | 分成三部分的基序蛋白32 | 2.1e-06 |
| C24G6.5(dnj-6) | 分子伴侣(DnaJ超家族)(伴侣) | DnaJ同源亚家族A成员2 | 1.9e-77 |
| T07F12.4 | 丝氨酸/苏氨酸-蛋白激酶(自噬蛋白) | ULK2蛋白 | 4.3e-29 |
| F32A6.3 | 膜泡组装/分类蛋白(vocuolarassemblyprotein/sorting | 膜泡组装蛋白VPS41同源蛋白的剪接异构体1 | 73-82 |
| protein)VPS41(白噬蛋白) | |||
| K11G12.4(smf-1) | NRAMP家族的Mn2+和Fe2+转运子(Mn/Fe转运子) | 二价金属转运子 | 3e-148 |
| F48E3.7(acr-22) | 乙酰胆碱受体亚单位 | 神经元乙酰胆碱受体蛋白，α9链前体 | 8e-50 |
本发明内容中“分离的”或“纯化的”的意思是从其自然环境中分离出来，其也基本不含有其他污染蛋白、多核苷酸和/或在细胞提取物中常见的其他生物物质。
本发明内容中的“多核苷酸”通常涉及多核糖核苷酸和多脱氧核糖核苷酸，它们可以是非修饰的RNA或DNA或者是修饰的RNA或DNA。多核苷酸分子包括编码蛋白的基因和KNA或者是非编码的RNA或DNA。
表1中所示的分子是根据线虫开放阅读框架(ORF)标识的名字列出的，本发明不局限于仅是C.elegans的序列。表1所列分子的其他物种同源物也适用于本发明，尤其是人同源物。C.elegans及相应人基因和蛋白的序列如下所示。相应的C.elegans核苷酸和蛋白序列以及人核苷酸和蛋白序列在表II中提供。
表2：
| C.elegansORF标识 | 名称 | 序列编号 | 序列来源及类型 |
| Y37A1B.13 | tor-2 | 1 | C.elegans核苷酸 |
| tor-2 | 2 | C.elegans蛋白 | |
| torsinA | 3 | 人核苷酸 | |
| torsinA | 4 | 人蛋白 |
| F57B10.5 | 5 | C.elegans核苷酸 | |
| 6 | C.elegans蛋白 | ||
| CGI-109 | 7 | 人核苷酸 | |
| CGI-109 | 8 | 人蛋白 | |
| R05D11.6 | 9 | C.elegans核苷酸 | |
| 10 | C.elegans蛋白 | ||
| MCG13017 | 11 | 人核苷酸 | |
| MCG13017 | 12 | 人蛋白 | |
| F16A11.2 | 13 | C.elegans核苷酸 | |
| 14 | C.elegans蛋白 | ||
| HSPC117 | 15 | 人核苷酸 | |
| HSPC117 | 16 | 人蛋白 | |
| F26E4.11 | 17 | C.elegans核苷酸 | |
| 18 | C.elegans蛋白 | ||
| 19 | 人核苷酸 | ||
| 20 | 人蛋白 | ||
| B0432.2 | 21 | C.elegans核苷酸 | |
| 22 | C.elegans蛋白 | ||
| DJ-1 | 23 | 人核苷酸 | |
| DJ-1 | 24 | 人蛋白 |
| EEED8.9 | PINK-1 | 25 | C.elegans核苷酸 |
| PINK-1 | 26 | C.elegans蛋白 | |
| PINK-1 | 27 | 人核苷酸 | |
| PINK-1 | 28 | 人蛋白 | |
| C35D10.2 | 29 | C.elegans核苷酸 | |
| 30 | C.elegans蛋白 | ||
| RGS19 | 31 | 人核苷酸 | |
| RGS19 | 32 | 人蛋白 | |
| F11H8.1 | rfl-1 | 33 | C.elegans核苷酸 |
| rfl-1 | 34 | C.elegans蛋白 | |
| E1C | 35 | 人核苷酸 | |
| E1C | 36 | 人蛋白 | |
| T13A10.2 | 37 | C.elegans核苷酸 | |
| 38 | C.elegans蛋白 | ||
| 39 | 人核苷酸 | ||
| 40 | 人蛋白 | ||
| M7.5 | 41 | C.elegans核苷酸 | |
| 42 | C.elegans蛋白 | ||
| E1-like | 43 | 人核苷酸 | |
| E1-like | 44 | 人蛋白 |
| T08D2.4 | 45 | C.elegans核苷酸 | |
| 46 | C.elegans蛋白 | ||
| 47 | 人核苷酸 | ||
| 48 | 人蛋白 | ||
| C24G6.5 | dnj-6 | 49 | C.elegans核苷酸 |
| dnj-6 | 50 | C.elegans蛋白 | |
| DnaJ | 51 | 人核苷酸 | |
| DnaJ | 52 | 人蛋白 | |
| T07F12.4 | 53 | C.elegans核苷酸 | |
| 54 | C.elegans蛋白 | ||
| ULK2 | 55 | 人核苷酸 | |
| ULK2 | 56 | 人蛋白 | |
| F32A6.3 | 57 | C.elegans核苷酸 | |
| 58 | C.elegans蛋白 | ||
| VPS41 | 59 | 人核苷酸 | |
| VPS41 | 60 | 人蛋白 | |
| K11G12.4 | smf-1 | 61 | C.elegans核苷酸 |
| smf-1 | 62 | C.elegans蛋白 | |
| 63 | 人核苷酸 | ||
| 64 | 人蛋白 |
| F48E3.7 | acr-22 | 65 | C.elegans核苷酸 |
| acr-22 | 66 | C.elegans蛋白 | |
| 67 | 人核苷酸 | ||
| 68 | 人蛋白 |
一个本领域内的技术人员可以认识到除人以外的生物也包括这些基因(例如真核生物、尤其是哺乳动物(特别是大猩猩、恒河猴和黑猩猩)、啮齿动物、线虫(例如C.elegans线虫)、昆虫(特别是黑腹果蝇)、鸟类、鱼类、酵母和植物)。本发明意在包括但不局限于从上述生物中分离出的编码表1所列蛋白的核酸分子。
这些基因的许多具有显著的进化保守度，显示了蛋白在物种之间的高度同源性。例如，人HSPC1 17与C.elegansF16Al 1.2同源，并且与黑腹果蝇(Drosophila melanogaster)(SEQ：69和70)、斑马鱼(Danio rerio)(SEQ：71和72)、牛(SEQ：73和74)、小鼠(SEQ：75和76)和大鼠(SEQ：77和78)基因/蛋白同源。所有这些序列都有基本为0的e值，说明基因在进化中高度保守。考虑到在结构上的高度同源性，这些序列在适当的表达水平下应该具有减少神经退化、蛋白错误折叠和聚集的相同功能。
本发明中分离的核酸分子也包括化学合成的核酸分子。例如，一个含有编码某基因表达产物的核苷酸序列构成的核酸分子可以设计和，如果需要分为适当的更小片段。然后可以合成与这个核酸分子或每一个分开片段相应的寡聚物。这样的合成寡核苷酸可以合成制备(Matteucci et al.，1981，JAm.Chem.Soc.103：3185-3191)或者通过使用自动DNA合成仪。一个寡核苷酸可以合成或者克隆得到。如果需要，寡核苷酸的5’端可以使用T4多核苷酸激酶磷酸化。寡核苷酸5’端的激酶活性提供了一种标记特定寡核苷酸的途径，可使用例如附加放射性同位素(通常是32P)到5’端的方法。其后，寡核苷酸可以通过T4链接酶或类似的酶进行退火和连接。
而且，利用由表2中序列来源的引物，通过多聚酶链式反应(PCR)制备的DNA序列对本发明是有用的。这样的寡核苷酸通常具有至少15个核苷酸的长度。
表1所列蛋白中的可产生相应模式的氨基酸序列和其使用是本发明所预期的。
与核酸序列相关的术语“基本由......组成”，被旨在用于说明书和权利要求书，以指对第三碱基简并性相关的核苷酸替代。如本领域内的技术人员可知，由于第三碱基简并性，几乎每一个氨基酸都可以用编码性核酸序列中的多于一个的三联体密码子所表示。进一步，小的碱基配对改变可以产生所编码氨基酸序列的多样性(保守替代)，而不会对基因产物的生物学活性产生实质的改变。这样，一个编码在本文所公开的蛋白或肽的核酸序列可以在序列轻微修饰(例如替代一个核苷酸的三联体密码子)后，仍编码其具有相同氨基酸序列的基因产物。
在此使用的多核苷酸序列内的“改变”是指利用敲除或击倒一个基因产生的或升高或降低的序列表达水平差异。也包括序列本身的不同，此不同对正确蛋白折叠和神经保护方面的效果具有和野生型蛋白所提供的一样。这样的改变包括升高或降低多核苷酸分子或蛋白的表达、突变、切断和缺失。从而，与编码如下蛋白的寡核苷酸分子杂交的DNA序列是本发明的组成成分，这些蛋白包括泛素-蛋白酶体降解系统蛋白、自噬蛋白、分子伴侣、转录因子、膜泡转运蛋白、Mn2+/Fe2+转运子、HSPCI 17蛋白、乙酰胆碱受体亚单位、DJ-I蛋白和PINK-I蛋白或者它们的片段。
技术人员可以找到通过杂交方法鉴定DNA序列的指导，所述杂交方法可被专家发现，其中有Boehringer Mannheim GmbH的“滤膜杂交DIG系统用户手册”(Mannheim，Germany，1993)和Liebl等人的International Journal ofSystematic Bacteriology′41：255-260(1991)。杂交在严格的条件下进行，即是说探针和靶序列(也就是寡核苷酸用探针处理)至少70％相同时杂合体才能形成。已知杂交的严格性，包括洗涤步骤，是由缓冲液组成、温度和盐浓度的变化影响和决定的。与洗涤步骤相比，杂交反应优选在相对较低严格条件下进行(Hybaid Hybridisation Guide，Hybaid Limited，Teddington，UK，1996)。
例如5x SSC缓冲溶液在大约50℃-68℃用于杂交反应。这样探针也可以与多核苷酸在与探针具有低于70％同一性的状况下杂交。这样的杂交稳定性较差，可以在严格条件下洗脱。上述杂交可以通过下述条件来实现，例如通过降低盐浓度到2xSSC和任选地其后降低至0.5xSSC，同时温度大约为50℃-68℃(滤膜杂交DIG系统用户手册，Boehringer Mannheim，Mannheim，Germany，1995)。一个可选择的可能是降低盐浓度到0.1xSSC。与探针序列具有如至少70％或至少80％或至少90％到95％的同一性的多核苷酸片段，可通过以大约每步1-2℃逐步从50℃升高杂交温度到68℃来分离。杂交的其他说明以试剂盒的形式可从市场上获得(例如DIG Easy Hyb，Roche Diagnostics GmbH，Mannheim，Germany，Catalogue No.1603558)。
“突变”是任何可检测到的遗传物质上的变化，其可以传递到子细胞中并且甚至可能转递到继代中产生突变细胞或突变个体。突变可以是影响到化学或物理组成、易变性、复制、表型功能或者一个或多个脱氧核糖核苷酸重组中任何一个(或其组合)可检测到的、非自然的变化；核苷酸可以在倒置或非倒置的情况下，添加、删除、替换，反转或转移到新位置上。在此使用的术语“突变”也指在编码文中所述蛋白的核酸序列上的任何修饰。例如，突变可以是点突变或者是添加、删除、插入和/或替换一个或多个核苷酸，或者是以上的组合。突变可以是错义或移码突变。修饰可以是，例如保守的或者不保守的，自然的或者非自然的。进一步可知，在蛋白N和/或C末端的变化不会产生实质性的损坏，或者可以稳定其功能。这一部分内容的信息可以被专家发现，其中有Ben-Bassat等{Journal of Bacteriology 169：751-757(1987))，O′Regan等{Gene77：237-251(1989))，Sahin-Toth等{Protein Sciences 3：240-247(1994))，Hochuli等(BioTechnology 6：1321-1325(1988))以及遗传和分子生物学的现有课本。突变可以通过与表2所列多核苷酸分子或其片段相应的多核苷酸分子的杂交来分离。
本发明也试图建立使用多肽分子，如旨在阻止蛋白错误折叠的蛋白的方法以及它们的使用方法。蛋白在表1中描述，氨基酸序列在表2中列出。这些蛋白优选地纯化或分离至物无污染蛋白、多核苷酸或其他污染化合物的基本纯净状态。
在此使用的蛋白中的“改变”是指蛋白在如野生型蛋白提供的辅助正确蛋白折叠和提供神经保护能力方面的变化。这样的改变包括如蛋白表达的变化、蛋白序列的突变和不同的剪接形式，尽管其他改变蛋白活性的变化也在考虑之中。
在另一个具体实施方式中，多肽具有表2所述的氨基酸序列或突变体或其变种；或与其具有至少70％同一性，进一步至少80％的同一性或更进一步至少90％同一性(优选地，至少90％，95％，96％，97％，98％，or 99％同一性或至少95％，96％，97％，98％，or 99％的相似性)，或至少6个相邻氨基酸(优选地，至少10、15、20、25或50个相邻氨基酸)。
本发明的蛋白质可以糖基化或非糖基化形式提供。糖基化蛋白质或其片段的制备是本领域内已知的，通常包括在真核细胞中表达编码该肽的重组DNA。另外，本领域内公知在原核细胞中表达编码该肽的重组DNA得到的肽是非糖基化的。这些和其他改变糖蛋白的糖部分的方法可见Essentials of Glycobiology(1999)，Edited By Ajit Varki，Cold Spring Harbor Laboratory Press，Cold SpringHarbor，NewYork，其内容已通过引用的方式纳入本文。
基本上由表1所列蛋白质的多肽序列组成的多肽分子也涵盖在内。
本发明的蛋白质可以包含一个或多个被保护的氨基酸残基。被保护的氨基酸是其一个或多个功能集团通过已知的方法用保护集团或多个保护集团保护起来的氨基酸，多种被保护的氨基酸可市购获得。蛋白质或其片段也可以包含一个或多个修饰氨基酸。这样氨基酸的列表可见美国专利2003/0235823，其全部内容已经通过引用的方式纳入本文。
虽然导入氨基酸序列变异的位点是预设的，但突变本身并无需预设。例如，为优化某一多肽的所期望活性的表现性能，对多肽的靶密码子或区域进行随机突变，再筛选表达的变异体以得到理想的期望活性。在已知序列的DNA预设位点进行替代突变的技术是已知的，例如定点突变。
氨基酸序列删除通常包括1到30个残基，更优选的是1到10个残基。氨基酸序列插入包括一个残基到基本上不限制长度的多肽的氨基和/或羧基端融合，也包括一个或多个氨基酸残基序列内的插入。序列内插入(即，在完整蛋白序列内的插入)通常包括大约1到10个残基，更优选的是1到5个。
第三组变异体是那些多肽分子上至少一个氨基酸残基，优选地只有一个残基，被去除并用一个不同的残基插入到其位置。
功能或免疫鉴定的实质性变化是通过选择具有较低保守性的取代来实现的，即选择功效更加显著不同的残基，其功效包括维持a)在取代区域内多肽骨架的结构，如片层构象或螺旋构象，b)靶点分子的电荷或疏水性，或c)侧链的体积。保守取代是取代氨基酸(自然发生或修饰的)与要被取代的氨基酸在结构上相关，例如与要被取代的氨基酸具有相同大小和带电性质。这样，取代氨基酸就具有了与原氨基酸相同或相似功能的集团。提供功能相似氨基酸的保守取代列表在本领域内是已知的。下述六个组，每组都包含可互相保守取代的氨基酸：
2)丙氨酸(A)、丝氨酸(S)、苏氨酸(T)；
3)天门冬氨酸(D)、谷氨酸(E)；
4)天门冬酰胺(N)、谷氨酰胺(Q)；
5)精氨酸(R)、赖氨酸(K)；
6)异亮氨酸(I)，亮氨酸(L)，甲硫氨酸(M)，缬氨酸(V)；
和
7)苯丙氨酸(F)、酪氨酸(Y)，色氨酸(W)。
进一步的取代包括：
a)甘氨酸和/或脯氨酸被另一个氨基酸取代或者删除或者插入；
b)亲水残基，例如丝氨酰基或苏氨酰基，取代疏水残基(例如亮氨氨酰、异亮氨酰、苯基丙氨酰、缬氨酰或丙氨酰)；
c)半胱氨酸残基取代其他任何残基；
d)具有正电侧链的残基，例如赖氨酰基、精氨酰或组氨酰，取代具有负电侧链的残基，例如谷氨酰或天门冬氨酰；或
e)具有大侧链的残基，例如苯丙氨酸，被取代不具有这样侧链的残基，例如甘氨酸。
一些删除、插入和取代认为不会产生对蛋白质性质的剧烈变化。本领域的技术人员可以认识到取代的效果可以使用如本文中公开的模型那样的动物模型或者化学和体内筛选分析来进行常规的评估。
在一个具体实施方式中，本发明涉及使用如表1中描述蛋白的表位来引发抗体反应的方法。选择抗原表位片段的方法在本领域内是已知的(Sutcliffe等，1983，Science.219：660-666)。本发明的抗原表位承载肽和多肽对升高特异识别多肽的免疫反应是有用的。本发明的抗原表位承载肽和多肽至少含有蛋白质的至少4个氨基酸(优选地是6、7、9、10、12、15或20个氨基酸)，该蛋白质的氨基酸序列变异体是表1中所列蛋白通过DNA上的突变来制备。这样的变异体包括，例如对表2所示氨基酸序列内的残基进行删除、插入或取代。假如最终结构具有期望的活性的话，可任意组合删除、插入和取代以获取最终的结构。在一个实施方式中，在本文描述的蛋白质用来制备特异于与该蛋白野生型或改变型相应的多肽序列的抗体。抗体也可用来作为探针或用于预防或治疗。
本发明提供了筛选错误折叠和蛋白聚集相关蛋白的方法。例如表1中所列的序列使用过表达人α-突触核蛋白::GFP融合蛋白的转基因线虫系筛选RNAi文库得到的。其他如GFP、RFP、BFP、YFP和荧光素酶等报告分子也可以以融合蛋白的形式与α-突触核蛋白一起表达。其他聚集倾向蛋白可以以此方式过表达来研究其他神经疾病的蛋白错误折叠和聚集，这些蛋白例如但不局限于：阿耳茨海默氏病的tau蛋白和β-淀粉样蛋白、亨廷顿舞蹈症中的突变亨廷顿蛋白，肌萎缩性侧索硬化症中的SOD1蛋白和神经丝以及脊髓性和延髓性肌肉萎缩中的突变雄性激素受体。特别提到帕金森综合症，在线虫C.elegans中过表达α-突触核蛋白导致在荧光显微镜下可见α-突触核蛋白聚集的形成。基因表达在unc-54启动子的控制下直接表达在机体外壁上以容易观察。TOR-2是表现出在过表达α-突触核蛋白的C.elegans中减少蛋白聚集的蛋白。包含α-突触核蛋白::GFP+TOR-2的转基因线虫系用于RNAi筛选与错误折叠和蛋白聚集相关的候选基因。TRO-2对错误折叠和蛋白聚集的相似抑制已经在之前作为多聚谷氨酰胺依赖的蛋白聚集报道过(Caldwell等，Hum MoI Genet.2003 Feb1；12(3)：307-19)。这一转基因线虫提供了使用RNAi饲喂含有α-突触核蛋白::GFP+TOR-2的转基因线虫体壁肌肉进行快速筛选的方法，用来发现使RNAi击倒基因表达引起的α-突触核蛋白聚集逆转的基因。使用RNAi通过常规方法可以对C.elegans基因文库进行筛选，从其中可重复的结果确定基因击倒对α-突触核蛋白聚集的效果。通常，对一个与蛋白聚集相关的靶基因，聚集表型在检测的α-突触核蛋白::GFP+TOR-2线虫中占大约80％。使用NCBIBLAST(NCBI，National Library of Medicine，NIH，Bethesda，MD)确定同源序列。
在另一个实施方式中，本发明的基因编码破坏对神经元的神经保护性能的蛋白。在此所教授的内容中，C.elegans基因文库用于筛选以确定一个候选基因是否为神经元提供了保护。例如，使用神经毒素6-OHDA处理导致C.elegans模型中多巴胺能神经元的损失。过表达挑选的基因阻止6-OHDA处理导致的多巴胺神经元损失。6-OHDA处理是通过形成活性氧产物导致损伤和死亡的。这样，6-OHDA处理提供了分析与活性氧产物相关的神经疾病的神经保护的模型。另外，可以建立表达神经疾病相关聚集倾向蛋白的神经疾病模型。例如，在C.elegans的多巴胺神经元中过表达人α-突触核蛋白模拟了帕金森综合症的神经退行性特征，因为这些动物在它们年老后表现处多巴胺神经元的损失(Cao等，J Neurosci.2005 Apr 13；25(15)：3801-12)。在本文中，转基因线虫代表了鉴定特定化合物和基因的神经保护功能的模型系统。
过表达靶基因的C.elegans的制备开始于表达神经元特异启动子控制下的荧光蛋白如GFP、RFP、BFP、荧光素酶或类似物的转基因线虫。神经元特异启动子是本领域内常规可用的启动子，包括但不局限于控制神经递质合成酶和神经递质转运子的启动子例如酪氨酸羟化酶、多巴胺β羟化酶、多巴胺转运子、复合胺转运子、膜泡乙酰胆碱转运子和类似物。
在另一实施方式中，本发明涉及使用核酸探针特异检测样品中相关核酸存在的方法，该相关核酸包括对应于上述核酸分子或至少其片段的DNA或RNA分子，其在严格杂交条件和洗脱条件下与核酸杂交。
在特定的应用中，对在本文描述的多核苷酸的检测可以被纳入至与表征与神经退行性疾病相关的蛋白错误折叠或聚集出现或倾向性的诊断分析。在一个优选的实施方式中，本发明涉及含有10至1000个核苷酸(优选的是10至500、10至100、10至50、10至35、20至1000、20至500、20至100、20至50或20至35)的分离核酸探针，其优先与RNA或DNA片段杂交，在此所说的核酸探针是或者互补于含有至少10个保守核苷酸(优选的是15、18、20、25或30个)的核苷酸序列，该保守核苷酸序列来源于含有与下述序列具有90％同一性的多核苷酸序列的核酸分子：编码表2所列多肽的核苷酸序列；与上述核苷酸序列互补的核苷酸序列；以及之前描述的任意核苷酸序列。
本发明的杂交探针可以被标记，以用于标准标记技术的检测，标准标记技术诸如放射性标记、荧光标记、生物素/亲和素标记、化学发光以及类似的方法。在杂交后，探针可以使用已知的方法可视化。
在另一个实施方式中，本发明涉及一种检测样品中某一核酸存在的方法，所述方法是通过如下步骤而实现的，即在可使杂交发生的特定杂交条件下使样品与上述核酸探针接触，并检测探针结合到核酸分子上。本领域的技术人员可基于如上所述本领域内的已知技术选择核酸探针。待测试的样品包括但不局限于人体组织来源的RNA或DNA样品。
适用于本发明核酸探针方法的待测样品包括，例如，细胞或细胞的核酸提取物或者生物液体。在本文描述的方法中使用的样品基于分析方式、检测方式以及分析中使用的组织、细胞或提取物的性质而发生变化。制备细胞核酸提取物的方法是本领域内已知的，并且易于调整以得到与所采用的方法相适应的样品。
本发明提供了通过检测与错误折叠/聚集或神经保护相关蛋白所发生的改变而进行神经疾病诊断的方法。在这些方法中，从个体得到的组织样品用以检测如下蛋白发生的改变，这些蛋白选自：泛素-蛋白酶体降解系统蛋白、自噬蛋白、分子伴侣、转录因子、膜泡运输蛋白、Mn2+/Fe2+转运子，HSPC1 17蛋白、乙酰胆碱受体亚单位、DJ-I蛋白和PINK-1蛋白，它们的改变显示了神经疾病的易患或出现。在此使用的“组织”是指从个体来源的生物样品。这样的样品的例子包括但不局限于细胞样品、单个细胞、机体液体样品如血液、淋巴或唾液，其样品中可能存在或不存在细胞。
在一个实施方式中，用于检测样品中以下蛋白：泛素-蛋白酶体降解系统蛋白、自噬蛋白、分子伴侣、转录因子、膜泡运输蛋白、Mn2+/Fe2+转运子，HSPC1 17蛋白、乙酰胆碱受体亚单位、DJ-I蛋白和PINK-1蛋白的方法包括：将样品与上述抗体(或蛋白)相接触，置于免疫复合物形成的条件下，再检测抗体与多肽的连接。特异结合的抗体或蛋白可以偶联上可检测的标签。详细地说，该方法包括将待测样品与一个或多个本发明的抗体一起温育以及分析抗体是否结合到待测样品上。与正常水平相比较，样品中蛋白水平或活性的改变能够表征一个特定的疾病。
在另外一个实施方式中，本发明涉及一种检测样品中对表1中蛋白特异的抗体的方法，其包括：将样品与表1中的蛋白相接触，置于免疫复合物形成的条件下，再检测蛋白连接到抗体或抗体连接到蛋白的发生。详细地说，该方法包括将待测样品与一个或多个本发明的抗体一起温育以及分析抗体是否结合到待测样品上。
温育抗体和待测样品的条件有多种。温育条件依赖于所采取分析的方式、所采取检测的方式和分析中所用抗体的性质和类型。本领域的技术人员可认识到任何常规可用的免疫学分析方式(例如放射性免疫测定、酶联免疫吸收测定、底层扩散平板(diffusion based Ouchterlony)或快速免疫荧光测定(rocketinimunofluorescent assays))都可以调整用于本发明的抗体(Chard，In：AnIntroduction to Radioimmunoassay and Related Techniques.Elsevier SciencePublishers，Amsterdam，The Netherlands(1986)；Bullock等，In：Techniques inImmunocytochemistry，Academic Press，Orlando，FIa.Vol.1(1982)，Vol.2(1983)，Vol.3(1985)；Tijssen，In：Practice and Theory of enzyme Immunoassays：Laboratory Techniques in Biochemistry and Molecular Biology，Elsevier SciencePublishers，Amsterdam，The Netherlands(1985))。
本发明的免疫分析待测样品包括细胞、蛋白质或细胞的膜提取物或者生物液体如血液、血清、血浆或尿。在上述方法中使用的待测样品由于分析方式、检测方法的性质和用于分析的样品为组织、细胞或提取物而有多种变化。制备细胞的蛋白提取物或细胞的膜提取物的方法是本领域内已知的，并且易于调整以得到适用于所采用系统的样品。
本要求保护的发明使用了几个合适的可测定聚集并引起神经疾病的蛋白的分析方法。合适的分析方法包括免疫方法，例如放射性免疫测定、酶联免疫吸收测定(ELISA)、化学发光测定和类似的方法。
在几个优选的实施方式中，免疫技术通过混合型抗体(例如一个或多个抗体)的方法检测表1中蛋白的水平，混合型抗体包括单克隆和/或多克隆抗体，以及它们的混合物。例如，这些免疫技术可以使用多克隆和/或单克隆抗体的混合物，诸如鼠单克隆和兔多克隆的混合。
本领域的技术人员可以得到针对适当免疫源的抗体，免疫源诸如分离的和/或重组的蛋白或者其片段或一部分(包括合成的分子，例如合成的肽)。在一个实施方式中，制备针对表1所列的分离的和/或重组的蛋白，或者其片段的一部分(例如肽)，或者针对表达这些重组蛋白之一的寄主细胞的抗体。另外，表达重组蛋白的细胞，如转染细胞，可以用来作为免疫源或用于结合蛋白的抗体的筛选。
根据此方法，测定可以确定生物样品中蛋白的水平或浓度。确定蛋白量的测定包括在抗体和蛋白形成复合物的合适条件下使待测样品与具有蛋白特异性的抗原结合，以及检测或测定(直接或间接)复合物的形成。样品可通过适用于特定样品(例如全血、组织提取物、血清)和所采用分析方式的方法获得和制备。例如，适用于全血收集的方法是静脉穿刺或从留置动脉导管收集血液。收集血液的容器含有抗凝血剂，如CACD-A、肝素或EDTA。选择结合样品和抗体的方法和检测复合物形成的方法与分析方式相适应。合适的标签可用于直接检测，如放射性、荧光或化学发光标签；或者使用诸如酶标和其他抗原或特异结合伴侣，如生物素和胶体金，进行间接检测。这样标签的例子包括荧光标签如荧光素、罗丹明、CY5和APC5，化学发光标签如荧光素酶，放射性同位素标签如32P、125I和131I，酶标签如辣根过氧化物酶，以及碱性磷酸酶、β牛乳糖、生物素、亲和素、自旋标记和类似的标记。复合物中抗体的检测也可使用第二抗体，第二抗体的免疫学检测在后续步骤进行。可以采用常规的或其他合适的方法直接或间接标记抗体。
在另一个实施方式中，表1所列的化合物可以用于诊断和筛选方法，其包括检测某一基因中突变是否存在，该基因的这种突变会造成人神经疾病。例如，本发明的诊断和筛选方法对诊断某些患者某一神经基因是否存在突变或多态性尤其有用，该患者根据其家族史被怀疑具有患与表1中蛋白表达水平改变相关的疾病，或者患者自愿检测与这些蛋白相关的疾病。
在另一个实施方式中，在本文描述的多核苷酸可开发成微阵列用于筛选突变的发生或者野生型序列或使个体易患神经失调的序列的缺失。微阵列包括在本文描述的野生型或改变的序列以检测由个体来源的组织样品中基因表达的变化。阵列包括本文中提到的所有序列或者与样品中互补序列特异结合的序列的片段和突变体。阵列也用于确认野生型基因表达的升高或降低，这些基因易于产生神经失调或表征神经失调的出现。任何情况下，阵列上提供了典型剂量的全长序列来检测组织样品来源的互补序列。多核苷酸的阵列或微阵列通常是核酸，例如DNA、RNA、PNA和cDNA，但也包括蛋白质、多肽、寡糖、细胞、组织和任何可以与靶分子特异结合的序列。微阵列的筛选包括使用对阵列上核酸序列特异的可检测的标签。筛选的实施可通过例如点样微阵列或依据说明书使用Affymetrix，Inc.(Santa Clara，Calif.)的片段DNA微阵列技术(要点说明见chena等.，Proc.Natl.Acad.Sci.USA 93：10614-10619，1996和Heller等，Proc.Natl.Acad.Sci.USA 94：2150-2155，1997)。分析基因表达的微阵列的使用可见综述Fritz等，Science 288：316，2000；Microarray Biochip Technology″，LShi，www.Gene-Chips.com。实施微阵列分析的系统和试剂可购于如Affymetrix，Inc.，Santa Clara Calif.；Gene Logic Inc.，Columbia Md.；HySeq Inc.，SunnyvaleCalif.；Molecular Dynamics Inc.，Sunnyvale Calif.；Nanogen，San Diego Calif.；andSynteni Inc.，Fremont Calif，(acquired by Incyte Genomics，Palo Alto Calif.)等公司。
“微阵列”和“阵列”在此可交替使用，是指在一集成区域内一系列核苷酸序列的排列。阵列可以置于固体物质诸如载玻片或半固体如硝化纤维素膜的表面上。核苷酸序列是DNA和RNA，但不局限于此。本领域内已知，微阵列指固定在基层(表面)上特定位置的单个多核苷酸或寡核苷酸的组合。形成阵列的基层可以由下列物质制作：纸质、玻璃、塑料(如聚丙烯和尼龙)、聚丙烯酰胺、硝化纤维素、硅、光学纤维、聚苯乙烯或其他任何合适的固体、半固体支持介质，并且制成平板(如玻璃板和硅芯片)或三维(如引脚、纤维、珠、颗粒、微孔和毛细管)结构。形成阵列的多核苷酸或寡核苷酸可通过数种方法连结到基层上，包括(i)使用照相平板印刷技术(见Fodor等，Science(1991)，251：767-773；Pease等，Proc.Natl.Acad.Sci.U.S.A.(1994)，91：5022-5026；Lockhart等，Nature Biotechnology(1996)，14：1675；U.S.Pat.Nos.5,578,832；5,556,752；和5,510,270)的原位合成(如高密度寡核苷酸阵列)；(ii)点样/印刷中或低密度(如cDNA探针)到玻璃、尼龙或硝化纤维素上(Schena等，Science(1995)，270：467-470，DeRisi等，Nature Genetics(1996)，14：457-460；Shalon等.，Genome Res.(1996)，6：639-645；and Schena等.，Proc.Natl.Acad.Sci.U.S.A.(1995)，93：10539-11286)；在尼龙或硝化纤维素杂交膜上(iii)利用掩模(Maskos和Southern，Nuc.Acids.Res.(1992)，20：1679-1684)和(iv)斑点印迹方法(见例如Sambrook等，Eds.，1989，Molecular Cloning：A LaboratoryManual，2nd ed.，Vol.1-3，Cold Spring Harbor Laboratory(Cold Spring Harbor，N.Y.))。
在一个实施方式中，在制备用于诊断神经失调的阵列时，微阵列包含与选自下述蛋白相关的序列：泛素-蛋白酶体降解系统蛋白、白噬蛋白、分子伴侣、转录因子、膜泡转运蛋白、Mn2+/Fe2+转运子、HSPCI 17蛋白、乙酰胆碱受体亚单位、DJ-I蛋白和PINK-I蛋白。
在另一个实施方式中，本发明涉及一种筛选激活或减弱表1中蛋白活性的化合物的方法。这些蛋白可以体外表达、纯化用于筛选分析或者在动物模型中表达用于蛋白错误折叠/聚集和神经毒性。对于随机筛选，随机选择如肽、碳水化合物、药物试剂和类似物的试剂并测定它们结合或激活/减弱蛋白活性的能力。这样的方法包括将表达蛋白的细胞和待测化合物一起温育；再通过测量化合物对该蛋白ATP结合的效果分析细胞的蛋白活性。任何细胞只要其表达功能形式的蛋白并且蛋白活性可测量，就可用于上述分析。优选的表达细胞是真核细胞或生物。这些细胞可以使用本领域内已知的常规手段改造以含有编码蛋白的DNA序列。可选地，本领域的技术人员可以直接将编码蛋白的mRNA导入细胞。
在另一个实施方式中，本发明涉及一种对医药品(如药物)的筛选，该医药品可以中和改变蛋白的表达或异常的活性。优选地，通过在本文描述的载体技术使用神经元培养物来过表达蛋白的突变形式。分析神经元形态和蛋白分布的变化并使用定量方法。此生物分析方法也作为筛选可以改善该表型的药物。使用表1中蛋白的配体(包括以上描述的拮抗剂和激动剂)，本发明进一步提供了一种调节蛋白活性的方法in a cen.m general，可制备鉴定可阻止或激活蛋白活性的药物(拮抗剂和激动剂)以使该化合物可以在体内与表达蛋白的细胞相接触。这样的细胞与这样化合物的接触导致在体内对该蛋白活性的调节。
候选化合物可选自传统分类的治疗试剂，例如小分子化合物、肽化合物、肽类似物、抗体、抗体片段、抗体衍生物、核苷酸、激素和其他类似物。
在一个实施方式中，候选小分子化合物包括拓扑异构酶II抑制剂、细菌钙通道阻遏物、转肽酶抑制剂、环氧合酶抑制剂、叶酸合成抑制剂和钠通道阻遏物。这些分子阻止了蛋白错误折叠和聚集或者提供了神经保护，具体可见美国临时专利申请60/738,761和60/749,910，它们的全部内容在此以引用的方式纳入本文。
在一个实施方式中，拓扑异构酶II抑制剂包括但不局限于洛美沙星、西诺沙星、胺苯吖啶、依托泊甙、替尼泊甙、恶喹酸、萘啶酸、苏拉明、麦尔巴隆、染料木黄酮、盐酸表阿霉素、椭圆玫瑰树碱、多柔比星或金精三羧酸(ATA)。
在另一个实施方式中，细菌转肽酶抑制剂包括但不局限于氨苄青霉素、氯唑西林、哌拉西林、阿莫西林、头孢羟氨苄、双氯唑西林、羧苄青霉素、青霉素、美坦西林、阿莫西林或cefoxatin。
在另一个实施方式中，钙通道阻遏物包括但不局限于尼莫地平、维拉帕米、尼群地平、地尔硫、易蒙停、氟桂利嗪、苄普地尔、利多氟嗪、CERM-196、R 58735、R-56865、雷诺嗪、尼索地平、尼卡地平、PN200-110、非洛地平、氨氯地平、R-(-)-202-791或R-(+)Bay K-8644。
在另一个实施方式中，环氧合酶抑制剂包括但不局限于萘普生、氟灭酸、托芬那酸、芬布芬、酮基布洛芬、非那西丁、安乃近、氟比洛芬、meclofenamide、吡罗昔康或美辛。
在另一个实施方式中，叶酸合成抑制剂包括但不局限于磺胺甲恶唑、磺胺嘧啶、磺胺多辛、氨苯砜、甲氧苄啶、二氯芦嘧啶、乙胺嘧啶或甲氨蝶呤。
在另一个实施方式中，钠通道阻遏物包括但不局限于利多卡因、盐酸达克罗宁、mexilitine、苯妥英、氯胺酮、氟卡胺或金刚烷胺。
本分析中筛选的其他试剂包括但不局限于肽、碳水化合物、维生素衍生物或其他医药试剂。这些试剂的选择和随机筛选通过使用例如蛋白或配体建模技术的方法合理的选择或设计(优选地，计算机建模)。
表1中描述的核苷酸序列和蛋白也可以用来设计新的可以作为内源分子激动剂、拮抗剂或结合伴侣发挥作用的化合物。通过在本文描述的筛选方法鉴定的活性检测试剂，其影响错误折叠和蛋白聚集，可以作为先导化合物用于合成类似化合物。通常，合成的类似化合物具有与先导化合物相似的电子构造和分子构象。类似化合物的鉴定可通过使用如下技术完成：如自洽场(self-consistent field，SCF)分析、构象相互作用(CI)分析和正常模式动态分析。已有执行这些技术的计算机程序。可参考Rein等，(1989)Computer-Assisted Modeling of Receptor-Ligand Interactions(Alan Liss，NewYork)。
一旦制备好类似物，它们就可以使用在本文公开的方法筛选以鉴定出那些调节蛋白聚集能力升高的类似物。这样的化合物在采取进一步分析以鉴定那些最有可以成为医药制剂的化合物。可选择地，在筛选方法中显示活性的类似物可在仍处在下一步分析的类似物的制备中作为先导化合物，其可通过在本文描述的方法筛选。筛选、合成类似物和再筛选的循环可重复多次。
可选择地，试剂可以合理地选择和设计。当一试剂基于蛋白构象来选择时，在此该试剂就被称为“合理选择或设计”。
定量结构-活性相关(QSAR)方法可用于量化化合物的化学结构和其生物学活性之间的关系。每一种化合物类型可通过一个或多个技术来定性或定级其广谱功效，这些技术包括结构-活性相关(SAR)和/或定量结构-活性相关(QSAR)方法，其鉴定与某类型化合物相关的一个或多个结构所涉及的一个或多个活性。这些化合物类型的每个都可以根据以下的因素如合成性、适应性、专一性、活性、毒性和/或新陈代谢来排定优先次序。在这种情形下，可以测定和分析每个特定化合物类型中所有化合物或附加群的化合物。由于一些化合物的类型十分庞大，可测定和分析化合物类型中的亚类并且如果该类继续表现出超过预计水平的功效，则剩余的成员将被继续测定。本方法也可鉴定用于本发明的化合物的功能类似物和化合物类型。功能类似物的活性再通过使用C.elegans模型筛选神经保护和对蛋白错误折叠和聚集的作用来予以确认。
计算机建模技术可使所选分子的三维原子结构可视化并合理设计与该分子相互作用的新化合物。这些方法提供了发现那些已知具有神经保护和蛋白错误折叠和聚集功能的小分子化合物的功能性类似物的途径。分析一个化合物结合到靶蛋白时的三维结构可鉴定出相互作用位点，该位点可用于鉴定具有相似结合特性的小分子化合物和功能性类似物。三维结构通常依赖于对所选分子的x射线晶体图像分析或NMR成像所得的数据。分子动力学需要力场数据。计算机图像系统使得预测一个新化合物如何连接到靶分子上成为可能，并且允许实验性制造化合物和靶分子的结构以得到完美结合特异性。当分子或化合物之一或都发生小变化时，预测分子-化合物相互作用会出现什么情况需要分子结构软件(molecular mechanics software)和集成计算计算机(computationallyintensive computers)，通常将分子设计程序与用户通过用户友好、菜单操作界面联系起来。
分子建模系统的例子有CHARMm和UANTA程序，olygen Corporation，Waltham，Mass。CHARMm具有能量最小化和分子动力学功能。QUANTA程序可执行建构、图形建模和分子结构分析。QUANTA运行互动式建构、修饰、可视化和分子间相互行为的分析。
一些文中综述了与特定蛋白相互作用药物的计算机建模。(Schneider andFechner，Nat Rev Drug Discov.2005 Aug；4(8)：649-63；Guner，IDrugs.2005Jul；8(7)：567-72；and Hanai，Curr Med Chem.2005；12(5)：501-25.)。其他筛选和图形预测化学物的计算机程序可从下述公司获得，如BioDesign，Inc.，Pasadena，Calif.，and Hypercube，Inc.，Cambridge，Ontario。尽管这些软件原本设计是用来应用对特定蛋白有特异性的药物，但它们也适合设计对DNA或RNA区域有特异性的药物，只要此区域已被鉴定。尽管上述内容涉及用于设计和制造可改变结合的化合物，但本领域的技术人员可筛选已知化合物，包括自然产物或合成化学物质、生物活性物质包括蛋白，以得到抑制剂或活化因子。使用这种方法鉴定的化合物的活性可通过使用C.elegans模型筛选神经对蛋白错误折叠和聚集的保护作用来予以确认。
本发明也提供了用于为预防和治疗性应用筛选化合物的转基因动物模型。本发明的转基因动物是导入了非自然物质(即人造的)，一个或多个在该动物不自然产生的基因(如外源基因，遗传工程的内源基因等)的动物。非自然的导入基因，称为转基因，可来自与该动物同种或不同种的动物，但不是该动物自然发现的，其以构象和/或染色体位点的形式通过转基因导入。
转基因包括外源DNA序列，即通常不在宿主动物基因组内发现的序列。可选择地或另外的，转基因包括内源DAN序列，所述的该内源DNA序列由于被重排或体外突变而非正常，目的是改变该基因正常的体内表达模式或者改变或降低该基因编码的内源基因产物的生物活性(Watson，J.D等，In：Recombinant DNA，2d Ed.，W.H.Freeman&Co.，New York(1992)，pg.255-272；Gordon，J.W.，1989，Intl.Rev.Cytol.115：171-229；Jaenisch，R.，1989，Science.240：1468-1474；Rossant，J.，1990，Neuron.2：323-334)。转基因可以与原核注射、ES细胞转染、病毒整合方法相结合，所有这些方法都是本领域内已知的常规技术。
本发明的非人类动物包括任何具有内源基因的打断或改变的动物(基因敲除动物)和/或基因组中被引入一个或多个针对从下述中所选蛋白表达的转基因的动物：泛素-蛋白酶体降解系统蛋白、自噬蛋白、分子伴侣、转录因子、膜泡转运蛋白、Mn2+/Fe2+转运子、HSPCI 17蛋白、乙酰胆碱受体亚单位、DJ-I蛋白和PINK-I蛋白。
这样的非人类动物包括脊椎动物如啮齿类、非人类灵长类、羊、狗、牛、两栖动物、爬行动物等。优选的非人类动物是选自非人类的哺乳动物物种，最优选的是啮齿类动物家族的成员包括大鼠和小鼠，最优选的是小鼠。
获得的转基因非人类动物对某疾病有易感性或转基因造成了某一疾病，可用来鉴定诱导该疾病的化合物和评估已知或怀疑诱导该疾病的化合物的治病潜能(Bems，A.J.M.，U.S.Pat..No.：5,174,986)，或者评估可用来治疗该疾病或缓解其症状的化合物(Scott，et al.，WO 94/12627)。
靶基因是整合到染色体上的，并且在这些转基因动物中过表达靶蛋白。
在一个实施方式中，本发明提供了转基因动物，其通过表达缺陷蛋白折叠机制或聚集倾向蛋白来展示与神经疾病相关的蛋白错误折叠和聚集的症状。其他聚集倾向蛋白如突变亨廷顿蛋白、β-淀粉样蛋白，tau蛋白，α-突触核蛋白、突变雄性激素受体、突变SODI、突变ataxin和类似物可以用来模拟其他神经疾病。在一个实施方式的一个实例中，使用了通过神经元特异启动子过表达α-突触核蛋白的转基因生物。过表达α-突触核蛋白产生了错误折叠蛋白中间体、蛋白聚集和神经元退化。这个转基因系可以与过表达靶基因的生物杂交，该靶基因在之前已经用RNAi筛选鉴定，杂交用来确定靶基因产物是否赋予了神经保护性能，是否降低了α-突触核蛋白错误折叠和聚集的毒性效应。其他模型可用于转基因是某基因的改变形式，基因选自：泛素-蛋白酶体降解系统蛋白、自噬蛋白、分子伴侣、转录因子、膜泡转运蛋白、Mn2+/Fe2+转运子、HSPCI 17蛋白、乙酰胆碱受体亚单位、DJ-I蛋白和PINK-I蛋白。改变形式包括导致神经疾病症状的蛋白表达增加或降低，或者突变，或者变化的剪接形式。
在一个测定神经保护的模型中，使用神经毒素如6羟色胺(6-OHDA)处理转基因动物，已知6羟色胺破坏含多巴胺的神经元。其他神经毒素也在本筛选方法中使用，并且是本领域内已知的常规技术。神经元多态性可在毒素暴露后使用荧光显微镜进行常规筛选。
例如，本筛选方法鉴定了一个基因产物，其特征是保护多巴胺能神经元免受6-OHDA伤害的能力。该C.elegans基因称为M7.5(SEQ ID NO：41)，对应于人E1样基因(SEQ ID NO：43)。该基因具有很高的保守性，在人、线虫、牛、大鼠和小鼠序列的e值是灵。这样，其他物种同源基因应该具有在提供神经保护方面相同的功能。过表达M7.5给予多巴胺神经元在暴露于神经毒素6-OHDA后的神经保护。相似地，扭转蛋白也给予多巴胺神经元在暴露于神经毒素6-OHDA后的神经保护(Cao等，J Neurosci.2005 Apr 13；25(15)：3801-12)。转基因线虫提供了筛选其他基因或化合物神经保护功效的模式系统。
当一个通常不生产该蛋白或通常产量很低的细胞通过遗传操作而可以产生某一蛋白时，如在此使用，该细胞被称为“改变以表达预期肽”。本领域内的技术人员易于改造程序以导入和表达其他基因组、cDNA或合成的序列到真核或原核细胞。
核酸分子，如DNA，如果它包含具有转录和翻译调节信息的核苷酸序列并且这样的序列“可操作地连接”到编码多肽的核苷酸序列上，就被称为“能够表达”某一多肽。可操作的连接是调节DNA序列和企图表达的DNA序列以此相连实现基因表达的连接。
在本文描述的核酸序列和蛋白质提供了医治神经疾病的治疗靶点。由基因或蛋白质缺乏或缺陷造成的神经疾病可通过恢复该基因或蛋白质的功能来治疗。这样的恢复可通过使用基因治疗或化合物给药来恢复正常基因或蛋白功能的方法来完成。
以某一方式和剂量提供功能DNA到已患或易患由蛋白缺乏或缺陷造成的神经疾病的患者的细胞内，使得这基因编码的蛋白得以表达，并且表达具有一定的时间和数量足以治疗这样的患者。本领域内已知许多载体系统可以为人类患者提供这样的转运，该患者需要某种细胞缺失的基因或蛋白。例如，可使用逆转录病毒系统，尤其是修饰的逆转录病毒和单纯疱疹病毒(Breakefield，X.O.等，1991，New Biologist.3：203-218；Huang，Q.等，1992，Experimental Neurology.115：303-316；WO93/03743；WO90/09441)。编码功能蛋白的DNA序列的转运会有效替换造成疾病的缺失或突变基因。
在本发明的另一实施方式中，基因以重组基因的形式在细胞内表达，这样该细胞可移植到哺乳动物中，优选的是需要基因治疗的人类。为个体提供基因治疗，将编码该基因全部或部分的遗传序列插入到载体中并导入到宿主细胞。在另一个实施方式中，缺陷或功能紊乱蛋白的表达可以使用RNAi来降低。这样的方法见综述Fore等(Curr Drug Targets.2005 Feb；6(l)：21-9)。
适用与基因治疗的疾病包括但不局限于神经退行性疾病或失调。这样的疾病包括帕金森氏病、阿耳茨海默氏病、朊病毒病、多谷氨酰胺病、tau蛋白病、亨廷顿舞蹈病、肌张力障碍、家族性肌萎缩性侧索硬化症、匹克病和皮质退化症。
可以使用基因治疗方法将表1中蛋白的编码序列转移到患者体内(Chattedee and Wong，1996，Curt：Top.Microbiol.Immunol.218：61-73；Zhang，1996，J.MoI.Med.74：191-204；Sclimidt-WoIf and Schmidt-Wolf，1995，J.Hematotherapy.4：551-561；Shaughnessy，et al.，1996，Seminars inOncology.23：159-171；Dunbar，I9964nnu.Rev.Med.47：11-20)。
在基因治疗中使用的载体包括但不局限于缺陷逆转录病毒、腺病毒或其他病毒载体(Mulligan，R.C，1993，Science.260：926-932)。携带基因的载体导入细胞的方法包括但不局限于显微注射、电穿孔、转导、使用DEAE-Dextran、脂质体和磷酸钙的转染或者其他本领域内已知的方式(Sambrook，J.，Fritsch，E.F.，and Maniatis，T.，1989，In：Molecular Cloning.A Laboratory Manual.，ColdSpring Harbor Laboratory Press，Cold Spring Harbor)。
本发明的化合物，包括使用所述筛选方法发现的治疗性化合物，可以给药来治疗神经疾病。在一个实施方式中，一个包含治疗用有效剂量化合物的药物组合物给药来治疗、降低或根除神经疾病的症状。本领域内的技术人员也会认识到任何治疗方案中的给药剂量是易于确定的。剂量应该不能大到产生有害副作用，如有害的交叉反应、过敏反应和类似的情况。通常，剂量依据病人的年龄、生理状况、性别和患病严重程度、禁忌症、以及其他变数而变化，由具体医师来调整。本发明中使用的用以提供免疫激活的剂量包括从大约1μg到大约500μg，其中包括0.5、1.0、1.5、2.0、5.0、10、15、20、25、30、35、40、45、50、55、60、65、70、75、80、85、90、95、100、150、200、250、300、350、400和450μg，包括彼此间的所有区间和亚区间。这样的量可以作为单一剂量给药或根据疗程，包括后续加大剂量，保证其有效，例如本发明的药物组合物可以一次给药或者在一定的天、周、月和/或年的时间内连续给药。配药可以随药物学上可接受的载体给药。
而且，配药的形式如可注射制剂(溶液、悬浊液、乳浊液使用时溶解的固体等)、药片、胶囊、颗粒、粉末、液体、脂质体包埋、药膏、凝胶、外用粉末、喷剂、吸入性粉末、滴眼液、眼药膏、栓剂、阴道栓剂和其他类似制剂根据给药的方式来适当地使用，本发明的肽从而可以形成。制药处方是本领域内普遍已知的，并且记述在如Comprehensive Medicinal Chemistry，Volume 5的25.2章(Editor Hansch等，Pergamon Press 1990)。
表1中的蛋白或其配体通过注射或逐渐灌注的办法非肠道给药。还可以静脉给药、腹膜腔内给药、肌内给药、鞘内给药或皮下给药。其他确认可透过血脑屏障的方法也适用于该化合物的给药。
非肠道给药制剂包括灭菌的水性或非水性的溶液、悬浊液和乳浊液。非水性溶液的例子有丙烯乙二醇、聚乙烯乙二醇、植物油如橄榄油和可注射有机脂如油酸乙酯。水性载体包括水、乙醇/水溶液、乳浊液或悬浊液，还包括盐和缓冲溶液。肠道载体包括氯化钠溶液、林格氏葡萄糖和氯化钠、乳化林格氏溶液或固定油。静脉载体包括液体和营养补充剂、电解液补充剂，例如基于林格氏葡萄糖的补充剂，和其他类似制剂。也可添加防腐剂和其他添加剂，例如抗菌剂、抗氧化剂、螯合剂、惰性气体和类似物(Remington′s PharmaceuticalScience，16th ed.，Eds.：Osol，A.，Ed.，Mack，Easton PA(1980))。
可用于本发明的药物学上可接受的载体包括但不局限于，例如粘结剂、润滑剂、着色剂、崩解剂、缓冲剂，等渗剂、防腐剂、麻醉剂和类似的在医药领域常用的试剂。
在另一个具体实施方式中，本发明涉及一种表1中蛋白或蛋白配体给动物(优选的是哺乳动物(更优选的是人类))给药的方法，其中给药量足以产生改变该动物体内该蛋白水平的功效。给药的蛋白或配体尤其对蛋白相关功能有效。而且，因为表1中的蛋白表达在脑组织中，蛋白或配体的给药可以用于改变脑中的蛋白水平或功能。可以用此方法治疗的神经失调包括蛋白聚集的失调如阿耳茨海默氏病、帕金森综合症、朊蛋白症、多谷氨酰胺病、tau蛋白病、亨廷顿舞蹈病、家族性肌萎缩性侧索硬化症、匹克病、进行性核上性麻痹和皮质退化症。
在另一个具体实施方式中，本发明设计一种用于检测样品中表1所列核酸或蛋白存在的试剂盒。在一个具体实施方式中，该试剂盒包括试剂和使用它们的说明书，其用于检测改变的蛋白或诊断神经疾病存在或易患倾向。该试剂盒包括至少一个含有上述核酸探针的容器。在一个优选的具体实施方式中，该试剂盒进一步包括其他含有洗涤试剂和/或可检测杂交核酸探针存在的试剂的容器。检测试剂包括但不局限于放射性探针、酶探针(辣根过氧化物酶、碱性磷酸酶)和亲和标记探针(生物素、亲和素或链酶亲和素)。在一个具体实施方式中，该试剂盒包括一个或多个用于检测失调的试剂，其是使用PCR、杂交或以序列为依据的分析或者任何上述方法的组合如微阵列。
详细来说，一个分隔式的试剂盒包括所包括任何其试剂都储存于单独容器内的试剂盒。这样的容器包括小玻璃容器、塑料容器或者塑料条或纸。这样的容器可以有效的将试剂从一个间隔转移到另一间隔，这样样品和试剂没有交叉污染，并且每个容器的试剂或溶液可以定量地从一个间隔添加到另一个。这样的容器包括可接受待测样品的容器、含有该测定中使用的探针或引物的容器、含有洗涤试剂(如磷酸盐缓冲液、Tris缓冲液和类似物)的容器和含有用于检测杂交探针、结合抗体、扩展产物或类似物的试剂的容器。
本领域的技术人员容易认识到本发明中描述的核酸探针易于加入到本领域内已知的制成的试剂盒中。
在本发明的另一个具体实施方式中，所提供试剂盒用于检测表1中蛋白是否存在；或由于表1中蛋白存在而在哺乳动物中产生的失调的可能性。本特定试剂盒包括实施前述检测方法的所有必须试剂。
例如，该试剂盒包括含有上述抗体的第一容器和含有结合物的第二容器，该结合物包含该抗体的结合伴侣和标签。
该试剂盒也包括含有上述蛋白的第一容器和优选地含有结合物的第二容器，该结合物包含该抗体的结合伴侣和标签。更特别的，诊断试剂盒包括如上述表1所列的某一蛋白质，以检测可能已感染的动物和人来源血浆中的抗体。
在另一个优选的具体实施方式中，试剂盒还包括一个或多个其他含有一个或多个如下成分的其他容器：洗涤试剂和能够检测结合抗体存在的试剂。检测试剂包括但不局限于标记的第二抗体、或可选择如果第一抗体是标记的时，是可与标记自显影相互作用的发光团的、酶的或抗体结合的试剂。分隔式试剂盒可如上所述用于核酸探针试剂盒。该试剂盒可包括例如RIA试剂盒或ELISA试剂盒。
本领域内的技术人员容易认识到本发明所描述的抗体易于加入到本领域内已知的制成的试剂盒中。
本发明将通过特别的实施例得到更详细的描述。以下提供实施例用于阐述本发明，并不用于限制本发明。
实施例1：使用RNAi筛选帕金森综合症中调节蛋白聚集的基因已培育出过表达α-突触核蛋白::GFP的转基因C.elegans系，其导致的α-突触核蛋白聚集可通过荧光显微镜观察到。基因表达处于unc-54启动子的控制下直接表达与体壁上。另一个含有α-突触核蛋白::GFP+TOR-2的转基因线虫系用来筛选与蛋白聚集相关的候选基因。在α-突触核蛋白::GFP+TOR-2线虫中，TOR-2的出现阻止了-突触核蛋白::GFP融合蛋白在体壁肌肉细胞内的聚集，导致扩散的荧光。TOR-2产生的相似蛋白抑制在之前作为多谷氨酰胺依赖蛋白聚集报道过(Caldwell等.Hum MoI Genet.2003 Feb l；12(3)：307-19)。此转基因生物允许在含有α-突触核蛋白::GFP+TOR-2的线虫体壁肌肉中使用RNAi饲喂的快速筛选方法，用来发现被RNAi消减后导致错误折叠升高和α-突触核蛋白聚集恢复的基因。
使用RNAi筛选C.elegans文库以确定基因击倒对α-突触核蛋白聚集的作用。购买这个含有18,000细菌菌株的RNAi文库用于在C.elegans中基因组RNAi筛选的细菌饲喂(Sanger Centre，Cambridge)。不同于在整个C.elegans中进行的广泛筛选，合理的基因靶向和微阵列表达数据鉴定出用于筛选的影响蛋白聚集的候选分子，所述的基因涉及内质网相关降解(ERAD)、泛素蛋白体系统(UPS)、自噬作用、帕金森综合症和蛋白质相互作用组。
简略的说，表达靶基因dsRNA的大肠杆菌新鲜培养物使用含有阿布青霉素和四环素的LB琼脂糖平板制备，并且生长过夜。幼α-突触核蛋白::GFP线虫的新鲜培养物和3mL表达靶基因的细菌ciuiures 01 me a.con在第二天制备。在实验当天，每个靶基因的一小、一中培养基平板用IPTG和细菌培养物涂布，涂布每种物质间保留晾干时间。每个中培养基平板上放5个L4线虫，在25摄氏度下放置大约42小时。所有的原始成体线虫再转移到小的IPTG/细菌涂布的平板上，放置9小时，然后烧死原始成虫。36小时后分析后代所产生表型的表达。
根据与蛋白聚集的关系，选择了一组共741个可能的基因目标，用于最初的RNAi筛选。所有的阳性候选基因再筛选第二次以消除假阳性结果。初次和二次筛选阐释了113个阳性基因。使用α-突触核蛋白::GFP+TOR-2线虫显示聚集的方法初次筛选这741个基因所鉴定出的基因的分布显示于图1b。
候选基因也在筛选过程中的所有阶段通过DJ-I和PINK1之间的微阵列实验鉴定。选择出共表达已知帕金森综合症基因DJ-I和PINK1的89个候选的样品。候选分子的覆盖显示于图2a。在两轮的RNAi筛选后，原89个基因组中的7个阳性候选改变α-突触核蛋白的聚集并且与DJ-I和PINK1共表达。有趣的是，2/7的阳性覆盖基因编码假基因。
多轮的RNAi分析(每个基因50个线虫；2次重复；当＞80％的线虫表现出升高的聚集认为是阳性)和在发育阶段动物中第二轮更严格的筛选，其用于鉴定随成熟表现更强效果的候选基因，鉴定了列于表1中的17个候选基因，这些基因在击倒后再生性地诱导人α-突触核蛋白的错误折叠。这些基因是DJ-I、PINK1和torsinA的C.elegans同源基因；4个UPS组分(1个E1链接酶、3个E3链接酶)、4个自噬机制的组分、一个预测的分子伴侣、1个牵扯膜泡运输的基因产物和3个之前未知功能的预测蛋白。
在系统RNAi击倒候选基因后，筛选α-突触核蛋白::GFP+TOR-2线虫聚集状态的恢复，得到了多种表型。这些表型包括在细胞核聚集的特殊斑块。
这些实验的发现提供了一种使用常规实验筛选与α-突触核蛋白聚集相关蛋白的可靠方法。这些实验的结果提供了对靶蛋白的鉴定，用于研究它们内引起病理表型的突变，同时提供了合理药物设计的蛋白目标。
实施例2：利用候选基因表达对多巴胺神经元在6-OHDA暴露后的神经保护
C.elegans含有明确的8个多巴胺能神经元，当其使用能6羟色胺(6-OHDA)、多巴胺类似物和神经毒素处理时表现出容易辨识的退化模式，这些物质可以在这些神经元内导致氧活性中间体的形成。在多巴胺神经元内过表达人torsinA或C.elegansTOR-2的任何一种，可以在α-突触核蛋白过表达或6-OHDA处理后急剧地抑制神经元退化(Cao等，JNeruosci，2005)。
蛋白聚集筛选的数据用于对随后的第三次筛选排序，此次用于筛选这些基因在多巴胺能神经保护方面可能的活性。在多巴胺神经元内表达GFP的转基因线虫已经构建成功并在6-OHDA暴露后广泛分析(Nass等2002；Cao等2005)。表型变化在暴露后2小时内出现，通常6小时绝大多数多巴胺神经元完全退化。编码RNAi筛选所得候选蛋白的cDNAs在多巴胺启动子(dat-1)控制下克隆以确定当在多巴胺神经元内表达时，这些候选帕金森综合症相关基因有些是否表现出神经保护活性。候选基因的野生型cDNAs克隆到dat-1启动子载体中，注射入线虫并在6-OHDA暴露后分析神经元保护。选择的候选基因在用于筛选帕金森综合症患者的基因组DNA。
而且，特别设计一个新的线虫同基因系用于筛选由神经保护显著的候选PD基因。这个新的同基因系包括在多巴胺神经元内染色体整合转基因过表达人α-突触核蛋白和GFP的，以在发育和成长中体内评估神经退化。这个线虫系在C.elegans发育的第4天成年期表现出大约30-40％退化，并且提供了研究α-突触核蛋白潜在破坏多巴胺神经退化的环境/遗传因素的理想工具。对阳性RNAi筛选候选基因的系统评估是通过在此α-突触核蛋白品系内，杂交多巴胺神经元内过表达相应cDNAs的动物和发现神经保护的证据来进行的。这一品系也用于α-突触核蛋白依赖退化的小分子抑制剂的中等通量筛选。
材料和方法
C.elegans品系和操作方案
使用标准程序(Brenner，1974)来培养线虫。通过用Pda；M7.5[strain UA38(baEx38)]或P(fa，.；::torsinA和P]，，.；::TOR-2转换P，/[alpha]/_/::GFP到野生型C.elegans(N2 Bristol variety)中。对α-突触核蛋白过表达系的构建，P，/a/./::GFPand Pjn，.；::[alpha]-synuclein[strain UA18(baExl[delta])]注射入N2线虫。对每一个重组质粒，多个表达稳定染色体外阵列的线虫系相比较，3个有代表性的线虫系用于处理6-OHDA以外的实验分析，而在所有稳定线虫系初次分析后，单个的代表性转基因线虫系用于重复实验。
质粒构建和突变
使用GatewayTM technology(Invitrogen，Carlsbad，CA)构建质粒。特别的，通过HindIII和Kpnl双酶切将unc-54启动子区从pPD30.38(Andrew Fire赠)切除，并用从pRN200(Nass等，2002)扩增的dat-1启动子区片段代替。所得的新载体再使用GatewayTM technology转入GatewayTM目的载体pDEST-DAT-1中。人α-突触核蛋白cDNA质粒从Philipp Kahle获得。Gateway插入载体通过BP反应制备，其使用编码M7.5(SEQ ID NO：41)α-突触核蛋白，GFP的cDNA片段PCR扩展得到的pDONR201或pDONR221。其后，所有的基因通过LR反应用相应的插入载体克隆到pDEST-DAT-1载体中。
制备用于免疫印迹的C.elegans提取物
在每一个转基因系生长到近乎汇集后制备提取物到两个100mm NGM平板上。线虫通过用M9缓冲液洗涤，在1.5ml离心管内5,000xg离心1分钟来收集。线虫沉淀在线虫裂解液(10OmM Tris，pH6.8，2％SDS，15％glycerol)中重悬并煮沸5分钟裂解。裂解物13,200xg离心10分钟，收集上清再使用CnetriconYM-10柱(Millipore)14,000xg离心x分钟。使用二辛可宁酸蛋白测定(Sigma，St.Louis，MO)确定蛋白浓度
SDS-PAGE和Western印迹
除有说明外，SDS-PAGE和Western印迹按照以前描述的方法进行(Caldwell等，2003)。对TRO-2检测，使用1∶800稀释的兔-抗-TRO-2一抗(Caldwell等，2003)和1∶10,000稀释的辣根过氧化物酶偶联的羊-抗-兔IgG二抗(Amersham-Pharmacia，Psicataway，NJ)。对actin检测，使用1∶800稀释的兔鼠-抗-actin抗体(ICN)和1∶10,000稀释的辣根过氧化物酶偶联的羊-抗-兔IgG二抗(Amersham-Pharmacia)。对GFP检测，140μg蛋白质上样，使用使用1∶10,000稀释的兔-抗-GFP一抗(Clontech，Palo Alto，CA)和1∶10,000稀释的辣根过氧化物酶偶联的羊-抗-兔IgG二抗(Amersham-Pharmacia，Psicataway)。
6-OHDA暴露和神经元退化的定量分析
通过用2％次氯酸钠、0.5M NaOH处理怀孕成虫来获得生长同步的线虫来分离胚胎(Lewis和Fleming，1995)。这些胚胎在25℃生长30小时。在L3期，幼虫使用10mM(或50mM)6-OHDA和2mM(或10mM)抗坏血酸温育1小时，期间每10分钟温柔搅拌一次(Nass等，2002)。线虫再经洗涤后涂布到接种了细菌(OP50)的NGM平板上，在6-OHDA暴露后从2到72小时每一时间点做记录。
在6-OHDA处理后，立即在荧光套色显微镜下根据GFP的存在情况选择含有非整合转基因的线虫，并转移到一个新鲜的接种OP50的NGM平板。在每一个时间点，将30-40个线虫置于2％琼脂糖膜上用3mM左旋咪唑固定。线虫在装有Endow GFP HYQ滤镜(Chroma)的Nikon Eclipse E800荧光显微镜下检查。为了分析的简单，只记录线虫头部的4个CEP多巴胺能神经元。当所有4个神经元都存在并且线虫神经元过程完好时，该线虫被记录为“野生型”；当至少4个神经元树突或胞体中的一个如描述中的缺陷时，该线虫被记录为“树突起泡”、“胞体圆化”或“胞体丢失”。这些实验重复3次。图像使用MetaMorph软件(Universal Imaging)驱动的a＞_ooi[omega]nap+-iy ouu相机(Photometries)捕捉。
α-突触核蛋白或CAT-2诱导的神经元保护分析
为得到α-突触核蛋白和CAT-2转基因系7天龄的动物，选择含绿色荧光非整合L1和L2的线虫并使其生长到4天(大约是孵化后7天)。分析每个非整合系在每个选定时期的30-40个线虫，每个转基因重组平均至少报道3个稳定系。但一个线虫无论树突形态如何，仍保存所有的CEP胞体时，就记录该线虫为野生型。
结果
候选基因的野生型cDNAs克隆入多巴胺表达载体用于转基因C.elegans内神经保护分析的评估。这一筛选方法通过显示某一自噬相关基因产物当其被RNAi击倒后，升高了α-突触核蛋白，还有torsin的错误折叠。一个同源基因，TOR-2当在C.elegans多巴胺神经元内特异过表达时，也表现出对6-OHDA暴露显著的神经保护作用。与对照线虫相比，在DA神经元内过表达野生型trosin(Pdat-1::torsinA和Pto.7::TOR-s)显著提高了DA神经元对10mM浓度的6-OHDA至少72内的抵抗力。此筛选方法也可鉴定一个具有保护多巴胺能神经元免受6-OHDA伤害功能的基因。该C.elegans基因称为M7.5(SEQ IDNNO：41)，对应于一个人E1样基因(SEQ ID NO：43)。此基因是泛素活化E1酶样蛋白家族的成员，在自噬反应中发挥作用。M7.5cDNA在GFP标记的多巴胺神经元内过表达并在6-OHDA暴露后分析神经保护作用。获得3个独立的M7.5表达转基因系。所有这3个品系都表现出保护多巴胺神经元免受6-OHDA诱导的氧化压力。此蛋白在DA神经元内的神经保护作用显示于图3。其他在发育早期表现出聚集和只在动物成熟后表现聚集的候选基因之间，进一步的研究显示出差别。
实施例3：使用微阵列检测蛋白改变的方法和对人体内帕金森综合症易感或出现的诊断。
帕金森综合症微阵列的制造
帕金森综合症微阵列的制作可以使用标准的商用微阵列技术，例如点样微阵列或Affymetrix公司的高密度寡核苷酸基本平台。选择中等到大量的基因和/或转录本来分析，例如，表达(或反应)谱。可使用本发明的方法监测的核酸序列包括但不局限于国家生物技术信息中心(在互联网ncbi.nlm.nih.gov)在GenBank.RTM数据库中所列的基因，和其他公共或商业数据库提供的序列(例如NCBI EST序列数据库、EMBL核苷酸序列数据库；Incyte’s(Palo Alto，Calif.)LifeSeq.TM.数据库和Celera’s(Rockville，Md.)“Discovery System”.TM.数据库)。本微阵列也包括编码表1中蛋白的人同源基因序列的相应转录本。本阵列可包括基因/转录本或者全长序列的一个或多个片段，其可以提供足以检测样品中基因/转录本的特异性。包含在微阵列上的是与SEQ ID NOs：3、7、11、15、19、23、27、31、35、39、43、47、51、55、59、63或67相应的转录本或片段已经它们的组合，包括这些序列的突变形式和剪接变体。其他包含在阵列上的序列包括其他与帕金森综合症相关的已知基因。与氧化压力和蛋白功能紊乱相关的基因序列也包含在微阵列上，因为已知这些生物过程在帕金森综合症中有作用(Miller等，Nenroscinetist.2005 Dec；11(6)：539-49)。其他与帕金森综合症相关的基因如SNPs也包含在此阵列上(Maraganore等，Am J Hum Genet.2005 Nov；77(5)：685-93)。此阵列也包括阳性对照和隐形对照。
帕金森综合症微阵列的使用
从个体收集组织样品，如生物活检，并使用标准方法制备微阵列探针，样品转换为标记的多核苷酸探针，杂交到微阵列上，而洗掉未连接的探针。其后使用常规阵列扫描仪扫描此阵列以检测标记并确认基因野生型或突变型出现与否(定性变化)以及患者样品中基因表达水平的变化(定量变化)。使用标准商用数据挖掘软件来分析和聚类遗传概貌。
使用微阵列所得的数据对药物基因组学和预测医学的应用是有用的。多个患者的遗传谱与症状程度、疾病的发生和严重程度相关从而构成了帕金森综合症概貌谱的数据库。患者谱也与患者对已有治疗方法如L-DOPA疗法的反应相关。新的治疗组合物的功效也与早期临床检验期间的患者谱相关从而确定某个新治疗的最佳遗传谱。
序列表
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Tyr Glu Asp Leu Lys Lys Asp Val Asp Thr Val Phe Glu Phe Gln Val
35 40 45
Val Thr Gly Gly His Tyr Asp Val Asp Leu Ile Ile Glu Asp Pro Asn
50 55 60
Gly Lys Val Leu Tyr Lys Asp Thr Lys Lys Gln Tyr Asp Ser Ile Asn
65 70 75 80
Phe Lys Ala Glu Val Glu Gly Thr Tyr Lys Ala Cys Phe Ser Asn Glu
85 90 95
Phe Ser Thr Phe Ser His Lys Ile Val Tyr Met Asp Trp Gln Phe Gly
100 105 110
Asp Gln Asn Ala Leu His Ala Ala Val Thr Gln Gly Ala His Ala Met
115 120 125
Thr Gln Leu Glu Asn Tyr Ala Val Ala Ile Gly Asp Lys Leu Arg Thr
130 135 140
Ile Asp Asp Tyr Gln Thr His His Arg Leu Arg Glu Ala Thr Gly Arg
145 150 155 160
Lys Arg Ala Glu Glu Leu Asn Glu Arg Val Met Ile Trp Ser Leu Gly
165 170 175
Gln Ser Ala Val Val Val Phe Ile Gly Ile Gly Gln Val Phe Leu Leu
180 185 190
Lys Ser Phe Phe Asn Asp Lys Arg Thr Arg Tyr
195 200
<210>7
<211>675
<212>DNA
<213>人
<220>
<221>CDS
<222>(1)..(675)
<400>7
atg ccg cgg ccg ggg tcc gcg cag cgc tgg gcg gcc gtc gcg ggc cgt 48
Met Pro Arg Pro Gly Ser Ala Gln Arg Trp Ala Ala Val Ala Gly Arg
1 5 10 15
tgg ggg tgc agg ctg ctc gca ctg ctg cta ctg gtg cct gga ccc ggc 96
Trp Gly Cys Arg Leu Leu Ala Leu Leu Leu Leu Val Pro Gly Pro Gly
20 25 30
ggc gcc tct gag atc acc ttc gag ctt cct gac aac gcc aag cag tgc 144
Gly Ala Ser Glu Ile Thr Phe Glu Leu Pro Asp Asn Ala Lys Gln Cys
35 40 45
ttc tac gag gac atc gct cag ggc acc aag tgc acc ctg gag ttc cag 192
Phe Tyr Glu Asp Ile Ala Gln Gly Thr Lys Cys Thr Leu Glu Phe Gln
50 55 60
gtg att act ggt ggt cac tat gat gta gat tgt cga tta gaa gat cct 240
Val Ile Thr Gly Gly His Tyr Asp Val Asp Cys Arg Leu Glu Asp Pro
65 70 75 80
gat ggt aaa gtg tta tac aaa gag atg aag aaa cag tat gat agt ttt 288
Asp Gly Lys Val Leu Tyr Lys Glu Met Lys Lys Gln Tyr Asp Ser Phe
85 90 95
acc ttc aca gcc tcc aaa aat ggg aca tac aaa ttt tgc ttc agc aat 336
Thr Phe Thr Ala Ser Lys Asn Gly Thr Tyr Lys Phe Cys Phe Ser Asn
100 105 110
gaa ttt tct act ttc aca cat aaa act gta tat ttt gat ttt caa gtt 384
Glu Phe Ser Thr Phe Thr His Lys Thr Val Tyr Phe Asp Phe Gln Val
115 120 125
gga gaa gac cca cct ttg ttt cct agt gag aac cga gtc agt gct ctt 432
Gly Glu Asp Pro Pro Leu Phe Pro Ser Glu Asn Arg Val Ser Ala Leu
130 135 140
acc cag atg gaa tct gcc tgt gtt tca att cac gaa gct ctg aag tct 480
Thr Gln Met Glu Ser Ala Cys Val Ser Ile His Glu Ala Leu Lys Ser
145 150 155 160
gtc atc gat tat cag act cat ttc cgt tta aga gaa gct caa ggc cga 528
Val Ile Asp Tyr Gln Thr His Phe Arg Leu Arg Glu Ala Gln Gly Arg
165 170 175
agc cga gca gag gat cta aat aca aga gtg gcc tat tgg tca gta gga 576
Ser Arg Ala Glu Asp Leu Asn Thr Arg Val Ala Tyr Trp Ser Val Gly
180 185 190
gaa gcc ctc att ctt ctg gtg gtt agc ata ggg cag gta ttt ctt ttg 624
Glu Ala Leu Ile Leu Leu Val Val Ser Ile Gly Gln Val Phe Leu Leu
195 200 205
aaa agc ttt ttc tca gat aaa aga acc acc aca act cgt gtt gga tca 672
Lys Ser Phe Phe Ser Asp Lys Arg Thr Thr Thr Thr Arg Val Gly Ser
210 215 220
taa 675
<210> 8
<211>224
<212>PRT
<213>人
<400>8
Met Pro Arg Pro Gly Ser Ala Gln Arg Trp Ala Ala Val Ala Gly Arg
1 5 10 15
Trp Gly Cys Arg Leu Leu Ala Leu Leu Leu Leu Val Pro Gly Pro Gly
20 25 30
Gly Ala Ser Glu Ile Thr Phe Glu Leu Pro Asp Asn Ala Lys Gln Cys
35 40 45
Phe Tyr Glu Asp Ile Ala Gln Gly Thr Lys Cys Thr Leu Glu Phe Gln
50 55 60
Val Ile Thr Gly Gly His Tyr Asp Val Asp Cys Arg Leu Glu Asp Pro
65 70 75 80
Asp Gly Lys Val Leu Tyr Lys Glu Met Lys Lys Gln Tyr Asp Ser Phe
85 90 95
Thr Phe Thr Ala Ser Lys Asn Gly Thr Tyr Lys Phe Cys Phe Ser Asn
100 105 110
Glu Phe Ser Thr Phe Thr His Lys Thr Val Tyr Phe Asp Phe Gln Val
115 120 125
Gly Glu Asp Pro Pro Leu Phe Pro Ser Glu Asn Arg Val Ser Ala Leu
130 135 140
Thr Gln Met Glu Ser Ala Cys Val Ser Ile His Glu Ala Leu Lys Ser
145 150 155 160
Val Ile Asp Tyr Gln Thr His Phe Arg Leu Arg Glu Ala Gln Gly Arg
165 170 175
Ser Arg Ala Glu Asp Leu Asn Thr Arg Val Ala Tyr Trp Ser Val Gly
180 185 190
Glu Ala Leu Ile Leu Leu Val Val Ser Ile Gly Gln Val Phe Leu Leu
195 200 205
Lys Ser Phe Phe Ser Asp Lys Arg Thr Thr Thr Thr Arg Val Gly Ser
210 215 220
<210>9
<211>1008
<212>DNA
<213>线虫
<220>
<221>CDS
<222>(1)..(1008)
<400>9
atg ggg aag tta gaa gac gtg gaa gct gaa aag aaa tta tgg gag agc 48
Met Gly Lys Leu Glu Asp Val Glu Ala Glu Lys Lys Leu Trp Glu Ser
1 5 10 15
gac gat gcg tgg gag ctc cga aaa gca ttc atg ctg gca cat tat gat 96
Asp Asp Ala Trp Glu Leu Arg Lys Ala Phe Met Leu Ala His Tyr Asp
20 25 30
gac tat ccg aaa atc caa ctt caa tgc ctc tca caa tta ttc att aat 144
Asp Tyr Pro Lys Ile Gln Leu Gln Cys Leu Ser Gln Leu Phe Ile Asn
35 40 45
gta aca ctt ctc gga tgt gaa tat tct cag act tta atg caa aag att 192
Val Thr Leu Leu Gly Cys Glu Tyr Ser Gln Thr Leu Met Gln Lys Ile
50 55 60
cga aca atg ggt gct gga att gct gct aac aaa gat cgt aca aaa act 240
Arg Thr Met Gly Ala Gly Ile Ala Ala Asn Lys Asp Arg Thr Lys Thr
65 70 75 80
gga agt tac gtg aag gca tct gca gcg aaa aag cga caa gca gtg aag 288
Gly Ser Tyr Val Lys Ala Ser Ala Ala Lys Lys Arg Gln Ala Val Lys
85 90 95
aca tca gat tta gaa gga gct tct gat gag tct aaa aaa gta aaa atg 336
Thr Ser Asp Leu Glu Gly Ala Ser Asp Glu Ser Lys Lys Val Lys Met
100 105 110
gaa aag tct cca tcg cca gta gct cgt gaa tct ttt gat gaa cgt ctt 384
Glu Lys Ser Pro Ser Pro Val Ala Arg Glu Ser Phe Asp Glu Arg Leu
115 120 125
gga aaa ctc aag gca tct ctt gca atg aca cct cac cat cta acg ggc 432
Gly Lys Leu Lys Ala Ser Leu Ala Met Thr Pro His His Leu Thr Gly
130 135 140
gaa caa atg atg aaa act gcc acg aat agt tgt ctc atg aag tgg cac 480
Glu Gln Met Met Lys Thr Ala Thr Asn Ser Cys Leu Met Lys Trp His
145 150 155 160
gtg aac aag att aac cag aaa att gaa ata act atc gat cga tat gtg 528
Val Asn Lys Ile Asn Gln Lys Ile Glu Ile Thr Ile Asp Arg Tyr Val
165 170 175
gcc ttc aga cat aca ttc tcc caa tac tgt gtt gat cca agg gat tgt 576
Ala Phe Arg His Thr Phe Ser Gln Tyr Cys Val Asp Pro Arg Asp Cys
180 185 190
gca atc aat act cta att gaa agc att ctt tcg tgt gac gcc gct gtt 624
Ala Ile Asn Thr Leu Ile Glu Ser Ile Leu Ser Cys Asp Ala Ala Val
195 200 205
cac gaa gaa agc tac gaa att aga ttt gat gga gtt ccg gtg gac gag 672
His Glu Glu Ser Tyr Glu Ile Arg Phe Asp Gly Val Pro Val Asp Glu
210 215 220
tgt tac gct aaa tca gtc acc aga aga ctt gca aaa att aaa tca gca 720
Cys Tyr Ala Lys Ser Val Thr Arg Arg Leu Ala Lys Ile Lys Ser Ala
225 230 235 240
gtt tct aat ggt gca cat aca gtt aaa ggt ctt aca aca tat ttg gat 768
Val Ser Asn Gly Ala His Thr Val Lys Gly Leu Thr Thr Tyr Leu Asp
245 250 255
gca gtt aac atg tca atg att caa aat act caa aaa ttg gaa gga tgg 816
Ala Val Asn Met Ser Met Ile Gln Asn Thr Gln Lys Leu Glu Gly Trp
260 265 270
tct caa caa ctt gat ctc gtc act gcc gat ctt ctt cta tct tct cgt 864
Ser Gln Gln Leu Asp Leu Val Thr Ala Asp Leu Leu Leu Ser Ser Arg
275 280 285
gtt tta tcc agc act gaa tgc act aaa cca gcg atg gca acg atc gcg 912
Val Leu Ser Ser Thr Glu Cys Thr Lys Pro Ala Met Ala Thr Ile Ala
290 295 300
aat caa atg agc gaa gac gtg tgt caa ctg att ctc aac gat aaa atc 960
Asn Gln Met Ser Glu Asp Val Cys Gln Leu Ile Leu Asn Asp Lys Ile
305 310 315 320
aac gtc att aac tct atg aaa tct cac agc tct ctt gca ttc caa taa 1008
Asn Val Ile Asn Ser Met Lys Ser His Ser Ser Leu Ala Phe Gln
325 330 335
<210>10
<211>335
<212>PRT
<213>线虫
<400>10
Met Gly Lys Leu Glu Asp Val Glu Ala Glu Lys Lys Leu Trp Glu Ser
1 5 10 15
Asp Asp Ala Trp Glu Leu Arg Lys Ala Phe Met Leu Ala His Tyr Asp
20 25 30
Asp Tyr Pro Lys Ile Gln Leu Gln Cys Leu Ser Gln Leu Phe Ile Asn
35 40 45
Val Thr Leu Leu Gly Cys Glu Tyr Ser Gln Thr Leu Met Gln Lys Ile
50 55 60
Arg Thr Met Gly Ala Gly Ile Ala Ala Asn Lys Asp Arg Thr Lys Thr
65 70 75 80
Gly Ser Tyr Val Lys Ala Ser Ala Ala Lys Lys Arg Gln Ala Val Lys
85 90 95
Thr Ser Asp Leu Glu Gly Ala Ser Asp Glu Ser Lys Lys Val Lys Met
100 105 110
Glu Lys Ser Pro Ser Pro Val Ala Arg Glu Ser Phe Asp Glu Arg Leu
115 120 125
Gly Lys Leu Lys Ala Ser Leu Ala Met Thr Pro His His Leu Thr Gly
130 135 140
Glu Gln Met Met Lys Thr Ala Thr Asn Ser Cys Leu Met Lys Trp His
145 150 155 160
Val Asn Lys Ile Asn Gln Lys Ile Glu Ile Thr Ile Asp Arg Tyr Val
165 170 175
Ala Phe Arg His Thr Phe Ser Gln Tyr Cys Val Asp Pro Arg Asp Cys
180 185 190
Ala Ile Asn Thr Leu Ile Glu Ser Ile Leu Ser Cys Asp Ala Ala Val
195 200 205
His Glu Glu Ser Tyr Glu Ile Arg Phe Asp Gly Val Pro Val Asp Glu
210 215 220
Cys Tyr Ala Lys Ser Val Thr Arg Arg Leu Ala Lys Ile Lys Ser Ala
225 230 235 240
Val Ser Asn Gly Ala His Thr Val Lys Gly Leu Thr Thr Tyr Leu Asp
245 250 255
Ala Val Asn Met Ser Met Ile Gln Asn Thr Gln Lys Leu Glu Gly Trp
260 265 270
Ser Gln Gln Leu Asp Leu Val Thr Ala Asp Leu Leu Leu Ser Ser Arg
275 280 285
Val Leu Ser Ser Thr Glu Cys Thr Lys Pro Ala Met Ala Thr Ile Ala
290 295 300
Asn Gln Met Ser Glu Asp Val Cys Gln Leu Ile Leu Asn Asp Lys Ile
305 310 315 320
Asn Val Ile Asn Ser Met Lys Ser His Ser Ser Leu Ala Phe Gln
325 330 335
<210>11
<211>351
<212>DNA
<213>人
<220>
<221>CDS
<222>(1)..(351)
<400>11
atg gtc ggt ggc gag gcg gct gcc gca gtg gag gag ctg gtt tcg ggg 48
Met Val Gly Gly Glu Ala Ala Ala Ala Val Glu Glu Leu Val Ser Gly
l 5 10 15
gtg cgg cag gcg gcc gac ttc gcg gag cag ttc cgc tcc tac tca gag 96
Val Arg Gln Ala Ala Asp Phe Ala Glu Gln Phe Arg Ser Tyr Ser Glu
20 25 30
agc gag aag caa tgg aag gcc cgc atg gaa ttc atc ctg cgc cac ctg 144
Ser Glu Lys Gln Trp Lys Ala Arg Met Glu Phe Ile Leu Arg His Leu
35 40 45
ccc gac tac cgc gac ccg ccc gac ggc agt ggc cgc ctg gac cag ctg 192
Pro Asp Tyr Arg Asp Pro Pro Asp Gly Ser Gly Arg Leu Asp Gln Leu
50 55 60
ctc tcc ctc tcc atg gtc tgg gcc aac cat ctc ttc cta ggc tgc agt 240
Leu Ser Leu Ser Met Val Trp Ala Asn His Leu Phe Leu Gly Cys Ser
65 70 75 80
tac aat aaa gac ctt tta gac aag gtg atg gaa atg gcc gat ggg att 288
Tyr Asn Lys Asp Leu Leu Asp Lys Val Met Glu Met Ala Asp Gly Ile
85 90 95
gaa gtg gaa gac ctg cca caa ttt act acc aga agt gaa tta atg aaa 336
Glu Val Glu Asp Leu Pro Gln Phe Thr Thr Arg Ser Glu Leu Met Lys
100 105 110
aag cat caa agc taa 351
Lys His Gln Ser
115
<210>12
<211>116
<212>PRT
<213>人
<400>12
Met Val Gly Gly Glu Ala Ala Ala Ala Val Glu Glu Leu Val Ser Gly
1 5 10 15
Val Arg Gln Ala Ala Asp Phe Ala Glu Gln Phe Arg Ser Tyr Ser Glu
20 25 30
Ser Glu Lys Gln Trp Lys Ala Arg Met Glu Phe Ile Leu Arg His Leu
35 40 45
Pro Asp Tyr Arg Asp Pro Pro Asp Gly Ser Gly Arg Leu Asp Gln Leu
50 55 60
Leu Ser Leu Ser Met Val Trp Ala Asn His Leu Phe Leu Gly Cys Ser
65 70 75 80
Tyr Asn Lys Asp Leu Leu Asp Lys Val Met Glu Met Ala Asp Gly Ile
85 90 95
Glu Val Glu Asp Leu Pro Gln Phe Thr Thr Arg Ser Glu Leu Met Lys
100 105 110
Lys His Gln Ser
115
<210>13
<211>1518
<212>DNA
<213>线虫
<220>
<221>CDS
<222>(1)..(1518)
<400>13
atg cct cgc aca ttt gaa gaa gaa tgt gat ttt atc gat cgc ttg aca 48
Met Pro Arg Thr Phe Glu Glu Glu Cys Asp Phe Ile Asp Arg Leu Thr
1 5 10 15
gac aca aag ttt cga att aag aaa ggt ttt gtg ccg aat atg aat gtg 96
Asp Thr Lys Phe Arg Ile Lys Lys Gly Phe Val Pro Asn Met Asn Val
20 25 30
gag gga cga ttt tat gtg aat aat agt ctc gaa caa tta atg ttt gac 144
Glu Gly Arg Phe Tyr Val Asn Asn Ser Leu Glu Gln Leu Met Phe Asp
35 40 45
gag tta aag ttc tca tgt gat gga caa gga atc ggt gga ttt ttg cca 192
Glu Leu Lys Phe Ser Cys Asp Gly Gln Gly Ile Gly Gly Phe Leu Pro
50 55 60
gcg gtc aga caa att gcc aac gtg gca tcc cta cca gga att gtt gga 240
Ala Val Arg Gln Ile Ala Asn Val Ala Ser Leu Pro Gly Ile Val Gly
65 70 75 80
cat tcg att ggt ctt cca gat att cac tct ggt tat ggt ttt tcc att 288
His Ser Ile Gly Leu Pro Asp Ile His Ser Gly Tyr Gly Phe Ser Ile
85 90 95
gga aac atc gct gcg ttc gac gtt gga aat cca gaa tct gta atc tca 336
Gly Asn Ile Ala Ala Phe Asp Val Gly Asn Pro Glu Ser Val Ile Ser
100 105 110
ccc gga ggc gtc ggt ttt gat atc aac tgt gga gta cga tta ctt cga 384
Pro Gly Gly Val Gly Phe Asp Ile Asn Cys Gly Val Arg Leu Leu Arg
115 120 125
acg aat ctt ttt gaa gaa aat gta aag cca tta aaa gaa caa cta aca 432
Thr Asn Leu Phe Glu Glu Asn Val Lys Pro Leu Lys Glu Gln Leu Thr
130 135 140
caa tca ctt ttt gat cat att cca gtt gga gtt ggt tca cgt ggt gca 480
Gln Ser Leu Phe Asp His Ile Pro Val Gly Val Gly Ser Arg Gly Ala
145 150 155 160
att cca atg ctt gca tca gat ctt gtt gaa tgt tta gaa atg gga atg 528
Ile Pro Met Leu Ala Ser Asp Leu Val Glu Cys Leu Glu Met Gly Met
165 170 175
gat tgg aca tta cgt gaa ggt tat tca tgg gca gaa gat aaa gaa cat 576
Asp Trp Thr Leu Arg Glu Gly Tyr Ser Trp Ala Glu Asp Lys Glu His
180 185 190
tgt gaa gaa tat gga cga atg tta caa gca gat gca tcg aaa gtt tca 624
Cys Glu Glu Tyr Gly Arg Met Leu Gln Ala Asp Ala Ser Lys Val Ser
195 200 205
ttg aga gct aaa aaa cgt gga ctt cca caa ttg gga act ctt gga gca 672
Leu Arg Ala Lys Lys Arg Gly Leu Pro Gln Leu Gly Thr Leu Gly Ala
210 215 220
gga aat cat tac gca gaa gtt caa gtt gtc gat gag att tat gat aaa 720
Gly Asn His Tyr Ala Glu Val Gln Val Val Asp Glu Ile Tyr Asp Lys
225 230 235 240
cat gct gca agt aca atg gga att gat gaa gaa ggg caa gtt gtt gta 768
His Ala Ala Ser Thr Met Gly Ile Asp Glu Glu Gly Gln Val Val Val
245 250 255
atg ctt cat tgt gga agt cga gga ctt gga cat caa gtt gca act gac 816
Met Leu His Cys Gly Ser Arg Gly Leu Gly His Gln Val Ala Thr Asp
260 265 270
tca tta gtt gaa atg gaa aaa gca atg gct aga gat gga att gtt gta 864
Ser Leu Val Glu Met Glu Lys Ala Met Ala Arg Asp Gly Ile Val Val
275 280 285
aat gat aag cag ctt gcg tgt gca aga att aat tcg gtt gaa ggc aaa 912
Asn Asp Lys Gln Leu Ala Cys Ala Arg Ile Asn Ser Val Glu Gly Lys
290 295 300
aac tac ttt tcc gga atg gcg gct gct gca aac ttc gcc tgg gtt aac 960
Asn Tyr Phe Ser Gly Met Ala Ala Ala Ala Asn Phe Ala Trp Val Asn
305 310 315 320
aga tcg tgt atc aca ttc tgt gtt cgt aat gca ttc caa aag aca ttt 1008
Arg Ser Cys Ile Thr Phe Cys Val Arg Asn Ala Phe Gln Lys Thr Phe
325 330 335
gga atg tca gca gat gat atg gat atg caa gta atc tat gac gtg tca 1056
Gly Met Ser Ala Asp Asp Met Asp Met Gln Val Ile Tyr Asp Val Ser
340 345 350
cat aat gta gca aaa atg gaa gag cat atg gtt gat ggt aga cca cgt 1104
His Asn Val Ala Lys Met Glu Glu His Met Val Asp Gly Arg Pro Arg
355 360 365
cag ctg tgt gtt cat cga aaa gga gct aca cgc gct ttt ccg gct cat 1152
Gln Leu Cys Val His Arg Lys Gly Ala Thr Arg Ala Phe Pro Ala His
370 375 380
cat cca tta ata cca gtt gat tat cag tta att gga caa cct gta cta 1200
His Pro Leu Ile Pro Val Asp Tyr Gln Leu Ile Gly Gln Pro Val Leu
385 390 395 400
att ggt gga agt atg gga act tgt agt tat gtt cta aca gga act gaa 1248
Ile Gly Gly Ser Met Gly Thr Cys Ser Tyr Val Leu Thr Gly Thr Glu
405 410 415
caa gga tta gtg gaa act ttt gga aca aca tgt cat gga gct gga cga 1296
Gln Gly Leu Val Glu Thr Phe Gly Thr Thr Cys His Gly Ala Gly Arg
420 425 430
gca ctt tca cgt gcc aaa tca cgc cga act atc act tgg gat tcg gta 1344
Ala Leu Ser Arg Ala Lys Ser Arg Arg Thr Ile Thr Trp Asp Ser Val
435 440 445
att gat gat ttg aaa aag aag gag atc tca att cgc att gca tcg cct 1392
Ile Asp Asp Leu Lys Lys Lys Glu Ile Ser Ile Arg Ile Ala Ser Pro
450 455 460
aaa ttg att atg gaa gaa gca ccc gaa tcg tat aag aat gtg acg gac 1440
Lys Leu Ile Met Glu Glu Ala Pro Glu Ser Tyr Lys Asn Val Thr Asp
465 470 475 480
gtt gta gac acg tgt gat gca gct ggc atc agt aaa aag gcg gtc aaa 1488
Val Val Asp Thr Cys Asp Ala Ala Gly Ile Ser Lys Lys Ala Val Lys
485 490 495
ctg aga cca att gcg gtc atc aag gga taa 1518
Leu Arg Pro Ile Ala Val Ile Lys Gly
500 505
<210>14
<211>505
<212>PRT
<213>线虫
<400>14
Met Pro Arg Thr Phe Glu Glu Glu Cys Asp Phe Ile Asp Arg Leu Thr
1 5 10 15
Asp Thr Lys Phe Arg Ile Lys Lys Gly Phe Val Pro Asn Met Asn Val
20 25 30
Glu Gly Arg Phe Tyr Val Asn Asn Ser Leu Glu Gln Leu Met Phe Asp
35 40 45
Glu Leu Lys Phe Ser Cys Asp Gly Gln Gly Ile Gly Gly Phe Leu Pro
50 55 60
Ala Val Arg Gln Ile Ala Asn Val Ala Ser Leu Pro Gly Ile Val Gly
65 70 75 80
His Ser Ile Gly Leu Pro Asp Ile His Ser Gly Tyr Gly Phe Ser Ile
85 90 95
Gly Asn Ile Ala Ala Phe Asp Val Gly Asn Pro Glu Ser Val Ile Ser
100 105 110
Pro Gly Gly Val Gly Phe Asp Ile Asn Cys Gly Val Arg Leu Leu Arg
115 120 125
Thr Asn Leu Phe Glu Glu Asn Val Lys Pro Leu Lys Glu Gln Leu Thr
130 135 140
Gln Ser Leu Phe Asp His Ile Pro Val Gly Val Gly Ser Arg Gly Ala
145 150 155 160
Ile Pro Met Leu Ala Ser Asp Leu Val Glu Cys Leu Glu Met Gly Met
165 170 175
Asp Trp Thr Leu Arg Glu Gly Tyr Ser Trp Ala Glu Asp Lys Glu His
180 185 190
Cys Glu Glu Tyr Gly Arg Met Leu Gln Ala Asp Ala Ser Lys Val Ser
195 200 205
Leu Arg Ala Lys Lys Arg Gly Leu Pro Gln Leu Gly Thr Leu Gly Ala
210 215 220
Gly Asn His Tyr Ala Glu Val Gln Val Val Asp Glu Ile Tyr Asp Lys
225 230 235 240
His Ala Ala Ser Thr Met Gly Ile Asp Glu Glu Gly Gln Val Val Val
245 250 255
Met Leu His Cys Gly Ser Arg Gly Leu Gly His Gln Val Ala Thr Asp
260 265 270
Ser Leu Val Glu Met Glu Lys Ala Met Ala Arg Asp Gly Ile Val Val
275 280 285
Asn Asp Lys Gln Leu Ala Cys Ala Arg Ile Asn Ser Val Glu Gly Lys
290 295 300
Asn Tyr Phe Ser Gly Met Ala Ala Ala Ala Asn Phe Ala Trp Val Asn
305 310 315 320
Arg Ser Cys Ile Thr Phe Cys Val Arg Asn Ala Phe Gln Lys Thr Phe
325 330 335
Gly Met Ser Ala Asp Asp Met Asp Met Gln Val Ile Tyr Asp Val Ser
340 345 350
His Asn Val Ala Lys Met Glu Glu His Met Val Asp Gly Arg Pro Arg
355 360 365
Gln Leu Cys Val His Arg Lys Gly Ala Thr Arg Ala Phe Pro Ala His
370 375 380
His Pro Leu Ile Pro Val Asp Tyr Gln Leu Ile Gly Gln Pro Val Leu
385 390 395 400
Ile Gly Gly Ser Met Gly Thr Cys Ser Tyr Val Leu Thr Gly Thr Glu
405 410 415
Gln Gly Leu Val Glu Thr Phe Gly Thr Thr Cys His Gly Ala Gly Arg
420 425 430
Ala Leu Ser Arg Ala Lys Ser Arg Arg Thr Ile Thr Trp Asp Ser Val
435 440 445
Ile Asp Asp Leu Lys Lys Lys Glu Ile Ser Ile Arg Ile Ala Ser Pro
450 455 460
Lys Leu Ile Met Glu Glu Ala Pro Glu Ser Tyr Lys Asn Val Thr Asp
465 470 475 480
Val Val Asp Thr Cys Asp Ala Ala Gly Ile Ser Lys Lys Ala Val Lys
485 490 495
Leu Arg Pro Ile Ala Val Ile Lys Gly
500 505
<210>15
<211>1518
<212>DNA
<213>人
<220>
<221>CDS
<222>(1)..(1518)
<400>15
atg agt cgc agc tat aat gat gag ctg cag ttc ttg gag aag atc aat 48
Met Ser Arg Ser Tyr Asn Asp Glu Leu Gln Phe Leu Glu Lys Ile Asn
1 5 10 15
aaa aac tgc tgg agg atc aag aag ggc ttc gtg ccc aac atg cag gtt 96
Lys Asn Cys Trp Arg Ile Lys Lys Gly Phe Val Pro Asn Met Gln Val
20 25 30
gaa ggt gtt ttc tat gtg aat gat gct ctg gag aaa ttg atg ttt gag 144
Glu Gly Val Phe Tyr Val Asn Asp Ala Leu Glu Lys Leu Met Phe Glu
35 40 45
gaa tta agg aat gcc tgt cga ggt ggt ggt gtt ggt ggc ttc ctg cca 192
Glu Leu Arg Asn Ala Cys Arg Gly Gly Gly Val Gly Gly Phe Leu Pro
50 55 60
gcc atg aaa cag att ggc aat gtg gca gcc ctg cct gga att gtt cat 240
Ala Met Lys Gln Ile Gly Asn Val Ala Ala Leu Pro Gly Ile Val His
65 70 75 80
cga tct att ggg ctt cct gat gtc cat tca gga tat ggg ttt gct att 288
Arg Ser Ile Gly Leu Pro Asp Val His Ser Gly Tyr Gly Phe Ala Ile
85 90 95
ggg aac atg gca gcc ttt gat atg aat gac cct gaa gca gta gta tcc 336
Gly Asn Met Ala Ala Phe Asp Met Asn Asp Pro Glu Ala Val Val Ser
100 105 110
cca ggt ggt gtc ggg ttt gac atc aac tgt ggt gtc cgc ttg cta aga 384
Pro Gly Gly Val Gly Phe Asp Ile Asn Cys Gly Val Arg Leu Leu Arg
115 120 125
acc aat tta gat gaa agt gat gtc cag cct gtg aag gag caa ctt gcc 432
Thr Asn Leu Asp Glu Ser Asp Val Gln Pro Val Lys Glu Gln Leu Ala
130 135 140
caa gct atg ttt gac cac att cct gtt ggg gtg ggg tca aaa ggt gtc 480
Gln Ala Met Phe Asp His Ile Pro Val Gly Val Gly Ser Lys Gly Val
145 150 155 160
atc cca atg aat gcc aaa gac ttg gag gag gcc ttg gag atg ggg gtg 528
Ile Pro Met Asn Ala Lys Asp Leu Glu Glu Ala Leu Glu Met Gly Val
165 170 175
gac tgg tcc tta aga gaa ggg tat gcc tgg gct gaa gac aag gag cac 576
Asp Trp Ser Leu Arg Glu Gly Tyr Ala Trp Ala Glu Asp Lys Glu His
180 185 190
tgc gag gag tac gga agg atg ctg cag gct gac ccc aat aaa gtt tct 624
Cys Glu Glu Tyr Gly Arg Met Leu Gln Ala Asp Pro Asn Lys Val Ser
195 200 205
gca agg gcg aag aaa aga ggc ctt cct cag ttg ggg acc ctg gga gca 672
Ala Arg Ala Lys Lys Arg Gly Leu Pro Gln Leu Gly Thr Leu Gly Ala
210 215 220
ggc aac cat tat gca gaa atc cag gtt gtg gat gag att ttc aat gag 720
Gly Asn His Tyr Ala Glu Ile Gln Val Val Asp Glu Ile Phe Asn Glu
225 230 235 240
tat gct gct aaa aaa atg ggc atc gac cat aag gga cag gtg tgt gtg 768
Tyr Ala Ala Lys Lys Met Gly Ile Asp His Lys Gly Gln Val Cys Val
245 250 255
atg atc cac agt gga agc aga ggc ttg ggc cac caa gta gcc aca gat 816
Met Ile His Ser Gly Ser Arg Gly Leu Gly His Gln Val Ala Thr Asp
260 265 270
gcg ctg gta gct atg gag aag gcc atg aag aga gac aag att ata gtc 864
Ala Leu Val Ala Met Glu Lys Ala Met Lys Arg Asp Lys Ile Ile Val
275 280 285
aat gat cgg cag ttg gct tgt gct cga atc gct tcc cca gag ggt caa 912
Asn Asp Arg Gln Leu Ala Cys Ala Arg Ile Ala Ser Pro Glu Gly Gln
290 295 300
gac tat ctg aag gga atg gca gct gct ggg aac tat gcc tgg gtc aac 960
Asp Tyr Leu Lys Gly Met Ala Ala Ala Gly Asn Tyr Ala Trp Val Asn
305 310 315 320
cgc tct tcc atg acc ttc tta acc cgt cag gct ttc gcc aag gtc ttc 1008
Arg Ser Ser Met Thr Phe Leu Thr Arg Gln Ala Phe Ala Lys Val Phe
325 330 335
aac aca acc cct gat gac ttg gac cta cat gtg att tat gat gtt tct 1056
Asn Thr Thr Pro Asp Asp Leu Asp Leu His Val Ile Tyr Asp Val Ser
340 345 350
cac aac att gcc aaa gtg gag cag cat gtg gtg gac gga aag gaa cgg 1104
His Asn Ile Ala Lys Val Glu Gln His Val Val Asp Gly Lys Glu Arg
355 360 365
aca ctg tta gta cac agg aag gga tcc acc cgc gct ttc cct cct cac 1152
Thr Leu Leu Val His Arg Lys Gly Ser Thr Arg Ala Phe Pro Pro His
370 375 380
cat ccc ctc att gct gtt gat tac caa ctc act gga cag cca gtg ctc 1200
His Pro Leu Ile Ala Val Asp Tyr Gln Leu Thr Gly Gln Pro Val Leu
385 390 395 400
att ggt ggc acc atg gga acc tgt agt tat gtt ctt act ggc act gaa 1248
Ile Gly Gly Thr Met Gly Thr Cys Ser Tyr Val Leu Thr Gly Thr Glu
405 410 415
cag ggc atg act gag acc ttt gga aca acc tgt cat gga gcg ggc cgt 1296
Gln Gly Met Thr Glu Thr Phe Gly Thr Thr Cys His Gly Ala Gly Arg
420 425 430
gca ttg tcc cga gca aaa tct cga cgt aat tta gat ttc cag gat gtc 1344
Ala Leu Ser Arg Ala Lys Ser Arg Arg Asn Leu Asp Phe Gln Asp Val
435 440 445
tta gac aaa ttg gca gat atg gga att gcg atc cgt gtt gcc tca ccc 1392
Leu Asp Lys Leu Ala Asp Met Gly Ile Ala Ile Arg Val Ala Ser Pro
450 455 460
aaa ctg gtt atg gaa gag gct cct gag tcc tat aag aat gtg aca gat 1440
Lys Leu Val Met Glu Glu Ala Pro Glu Ser Tyr Lys Asn Val Thr Asp
465 470 475 480
gtg gta aat acc tgc cat gat gct gga atc agc aag aaa gcc att aaa 1488
Val Val Asn Thr Cys His Asp Ala Gly Ile Ser Lys Lys Ala Ile Lys
485 490 495
ctg aga cca att gct gtg atc aaa gga tag 1518
Leu Arg Pro Ile Ala Val Ile Lys Gly
500 505
<210>16
<211>505
<212>PRT
<213>人
<400>16
Met Ser Arg Ser Tyr Asn Asp Glu Leu Gln Phe Leu Glu Lys Ile Asn
1 5 10 15
Lys Asn Cys Trp Arg Ile Lys Lys Gly Phe Val Pro Asn Met Gln Val
20 25 30
Glu Gly Val Phe Tyr Val Asn Asp Ala Leu Glu Lys Leu Met Phe Glu
35 40 45
Glu Leu Arg Asn Ala Cys Arg Gly Gly Gly Val Gly Gly Phe Leu Pro
50 55 60
Ala Met Lys Gln Ile Gly Asn Val Ala Ala Leu Pro Gly Ile Val His
65 70 75 80
Arg Ser Ile Gly Leu Pro Asp Val His Ser Gly Tyr Gly Phe Ala Ile
85 90 95
Gly Asn Met Ala Ala Phe Asp Met Asn Asp Pro Glu Ala Val Val Ser
100 105 110
Pro Gly Gly Val Gly Phe Asp Ile Asn Cys Gly Val Arg Leu Leu Arg
115 120 125
Thr Asn Leu Asp Glu Ser Asp Val Gln Pro Val Lys Glu Gln Leu Ala
130 135 140
Gln Ala Met Phe Asp His Ile Pro Val Gly Val Gly Ser Lys Gly Val
145 150 155 160
Ile Pro Met Asn Ala Lys Asp Leu Glu Glu Ala Leu Glu Met Gly Val
165 170 175
Asp Trp Ser Leu Arg Glu Gly Tyr Ala Trp Ala Glu Asp Lys Glu His
180 185 190
Cys Glu Glu Tyr Gly Arg Met Leu Gln Ala Asp Pro Asn Lys Val Ser
195 200 205
Ala Arg Ala Lys Lys Arg Gly Leu Pro Gln Leu Gly Thr Leu Gly Ala
210 215 220
Gly Asn His Tyr Ala Glu Ile Gln Val Val Asp Glu Ile Phe Asn Glu
225 230 235 240
Tyr Ala Ala Lys Lys Met Gly Ile Asp His Lys Gly Gln Val Cys Val
245 250 255
Met Ile His Ser Gly Ser Arg Gly Leu Gly His Gln Val Ala Thr Asp
260 265 270
Ala Leu Val Ala Met Glu Lys Ala Met Lys Arg Asp Lys Ile Ile Val
275 280 285
Asn Asp Arg Gln Leu Ala Cys Ala Arg Ile Ala Ser Pro Glu Gly Gln
290 295 300
Asp Tyr Leu Lys Gly Met Ala Ala Ala Gly Asn Tyr Ala Trp Val Asn
305 310 315 320
Arg Ser Ser Met Thr Phe Leu Thr Arg Gln Ala Phe Ala Lys Val Phe
325 330 335
Asn Thr Thr Pro Asp Asp Leu Asp Leu His Val Ile Tyr Asp Val Ser
340 345 350
His Asn Ile Ala Lys Val Glu Gln His Val Val Asp Gly Lys Glu Arg
355 360 365
Thr Leu Leu Val His Arg Lys Gly Ser Thr Arg Ala Phe Pro Pro His
370 375 380
His Pro Leu Ile Ala Val Asp Tyr Gln Leu Thr Gly Gln Pro Val Leu
385 390 395 400
Ile Gly Gly Thr Met Gly Thr Cys Ser Tyr Val Leu Thr Gly Thr Glu
405 410 415
Gln Gly Met Thr Glu Thr Phe Gly Thr Thr Cys His Gly Ala Gly Arg
420 425 430
Ala Leu Ser Arg Ala Lys Ser Arg Arg Asn Leu Asp Phe Gln Asp Val
435 440 445
Leu Asp Lys Leu Ala Asp Met Gly Ile Ala Ile Arg Val Ala Ser Pro
450 455 460
Lys Leu Val Met Glu Glu Ala Pro Glu Ser Tyr Lys Asp Val Thr Asp
465 470 475 480
Val Val Asn Thr Cys His Asp Ala Gly Ile Ser Lys Lys Ala Ile Lys
485 490 495
Leu Arg Pro Ile Ala Val Ile Lys Gly
500 505
<210>17
<211>1695
<212>DNA
<213>线虫
<220>
<221>CDS
<222>(1)..(1695)
<400>17
atg ggg gtt gtc aat cta cta tcc cga tca tca ttt cca tct gtc gac 48
Met Gly Val Val Asn Leu Leu Ser Arg Ser Ser Phe Pro Ser Val Asp
1 5 10 15
tca tat ctg gca ttg tca gtt ctt gtt gca att gtt gct tct gtc act 96
Ser Tyr Leu Ala Leu Ser Val Leu Val Ala Ile Val Ala Ser Val Thr
20 25 30
gta ttt aca aca ttt cgc tca caa ccc gag cta cag aag ctt atc gaa 144
Val Phe Thr Thr Phe Arg Ser Gln Pro Glu Leu Gln Lys Leu Ile Glu
35 40 45
gaa gaa ctt cgg aat aat aca cga ctg tca tca gca tat ggt ttg aat 192
Glu Glu Leu Arg Asn Asn Thr Arg Leu Ser Ser Ala Tyr Gly Leu Asn
50 55 60
att gaa gca ttg tcc ggg cac aca ttc ttt caa att gct cat tac att 240
Ile Glu Ala Leu Ser Gly His Thr Phe Phe Gln Ile Ala His Tyr Ile
65 70 75 80
tta tct gat aca acg cta atc tgg gtt gct ata aac tcg tat ttt gcc 288
Leu Ser Asp Thr Thr Leu Ile Trp Val Ala Ile Asn Ser Tyr Phe Ala
85 90 95
ata cta gca gtt tgt acg aga cta ata atc aaa tta aca ttc aaa gag 336
Ile Leu Ala Val Cys Thr Arg Leu Ile Ile Lys Leu Thr Phe Lys Glu
100 105 110
ctc gcc cga cag gag gaa aat gtg gcc cgt caa gct ttc ttc tgt tat 384
Leu Ala Arg Gln Glu Glu Asn Val Ala Arg Gln Ala Phe Phe Cys Tyr
115 120 125
gtc ctg tta aca atc gtc tac tta tca gtt gtg atc gga ccg caa aag 432
Val Leu Leu Thr Ile Val Tyr Leu Ser Val Val Ile Gly Pro Gln Lys
130 135 140
ggg cat cgt gta atg cca tgg atg atc tgg ggt ggt att tgt gct ttc 480
Gly His Arg Val Met Pro Trp Met Ile Trp Gly Gly Ile Cys Ala Phe
l45 150 155 160
tta tcc cat ttg cag ttt atc aca tgt cag agg ctc aag cat atc tct 528
Leu Ser His Leu Gln Phe Ile Thr Cys Gln Arg Leu Lys His Ile Ser
165 170 175
cca tcc tgt gat cgt gga agt cag aag att tca ttc ctc tcg ttg ttc 576
Pro Ser Cys Asp Arg Gly Ser Gln Lys Ile Ser Phe Leu Ser Leu Phe
180 185 190
ctc ttc ttc gtt tcg att gcc atg acg ttc ttg att tct cga ttc caa 624
Leu Phe Phe Val Ser Ile Ala Met Thr Phe Leu Ile Ser Arg Phe Gln
195 200 205
cat cac tta aca tgg caa cct gct gta ctt tta tat ttt gat tgc ctt 672
His His Leu Thr Trp Gln Pro Ala Val Leu Leu Tyr Phe Asp Cys Leu
210 215 220
ctc gca gta ttc cgt tcc act tac att ctg ttc cga tgc att tct tca 720
Leu Ala Val Phe Arg Ser Thr Tyr Ile Leu Phe Arg Cys Ile Ser Ser
225 230 235 240
tct cgt gta ttc tcc ttc aat cct gac tct gtt cgt cat ttc aac tat 768
Ser Arg Val Phe Ser Phe Asn Pro Asp Ser Val Arg His Phe Asn Tyr
245 250 255
tgg ctc gag ctt atc acc aac ttt gtc tgc gaa ctc att caa atg ctc 816
Trp Leu Glu Leu Ile Thr Asn Phe Val Cys Glu Leu Ile Gln Met Leu
260 265 270
agt ttt gct caa ctt ttg gca ttc tca cct gga ctt aat ctc aca agc 864
Ser Phe Ala Gln Leu Leu Ala Phe Ser Pro Gly Leu Asn Leu Thr Ser
275 280 285
atc ttc ttc ttg tat cac atg aag ctt acc tac aac tgc atg act gaa 912
Ile Phe Phe Leu Tyr His Met Lys Leu Thr Tyr Asn Cys Met Thr Glu
290 295 300
caa tta agt cgt cat cgt aat cat aag aag atc ttc gaa cac att gag 960
Gln Leu Ser Arg His Arg Asn His Lys Lys Ile Phe Glu His Ile Glu
305 310 315 320
aga tca tat cca agt gtt aaa tgt gct aat ggt gat gat cgt tgc gtt 1008
Arg Ser Tyr Pro Ser Val Lys Cys Ala Asn Gly Asp Asp Arg Cys Val
325 330 335
gtt tgc tgg gaa ttg ctc gga aca tct cga aga ctt cca tgc tct cat 1056
Val Cys Trp Glu Leu Leu Gly Thr Ser Arg Arg Leu Pro Cys Ser His
340 345 350
caa ttc cat gat tgg tgt ctc atg tgg tgg ctt gct cag gat tct tca 1104
Gln Phe His Asp Trp Cys Leu Met Trp Trp Leu Ala Gln Asp Ser Ser
355 360 365
tgt cca acg tgt cgt tgt act att cca tct cca caa gat caa atc aga 1152
Cys Pro Thr Cys Arg Cys Thr Ile Pro Ser Pro Gln Asp Gln Ile Arg
370 375 380
caa cca cca gag gtt gga aat agt aca aga tta cgt ttc aat ggt gga 1200
Gln Pro Pro Glu Val Gly Asn Ser Thr Arg Leu Arg Phe Asn Gly Gly
385 390 395 400
tca ttt gga ttc gtt cat ttc cca gca ttc act ctt gaa gta gct gct 1248
Ser Phe Gly Phe Val His Phe Pro Ala Phe Thr Leu Glu Val Ala Ala
405 410 415
aac ttc ggg cct ttc ttt ggt cga gca gcc gaa cca aca gaa gag caa 1296
Asn Phe Gly Pro Phe Phe Gly Arg Ala Ala Glu Pro Thr Glu Glu Gln
420 425 430
ttg caa aca atg ctc gag caa gtc agg gag atg ttc ccg cag atg tct 1344
Leu Gln Thr Met Leu Glu Gln Val Arg Glu Met Phe Pro Gln Met Ser
435 440 445
gtt gat ata ata atg acg gat cta cga caa tcg gga tcc gct cag tct 1392
Val Asp Ile Ile Met Thr Asp Leu Arg Gln Ser Gly Ser Ala Gln Ser
450 455 460
aca atc gaa aat att cta gaa gga agg ata gga atg aat gca tca ttt 1440
Thr lle Glu Asn Ile Leu Glu Gly Arg Ile Gly Met Asn Ala Ser Phe
465 470 475 480
atg ccc ggt ggg gtt ttg gat gat gaa ctc tca gat gag agt gaa aac 1488
Met Pro Gly Gly Val Leu Asp Asp Glu Leu Ser Asp Glu Ser Glu Asn
485 490 495
gaa ata gaa tat gaa gag ccc gcc gaa ata gtc caa gaa cca gat aat 1536
Glu Ile Glu Tyr Glu Glu Pro Ala Glu Ile Val Gln Glu Pro Asp Asn
500 505 510
ggc cgt caa aga acg tgg aca aaa ttg agt tct tca tca gga gat gaa 1584
Gly Arg Gln Arg Thr Trp Thr Lys Leu Ser Ser Ser Ser Gly Asp Glu
515 520 525
gat cta tca tac tat gaa atc cag cga gcc aaa atg atc gaa act tac 1632
Asp Leu Ser Tyr Tyr Glu Ile Gln Arg Ala Lys Met Ile Glu Thr Tyr
530 535 540
cga cgg aaa tat ctg gag tct gat aaa gct gcc gat cta cga gca atg 1680
Arg Arg Lys Tyr Leu Glu Ser Asp Lys Ala Ala Asp Leu Arg Ala Met
545 550 555 560
gga atc acc gaa taa 1695
Gly Ile Thr Glu
<210>18
<211>564
<212>PRT
<213>线虫
<400>18
Met Gly Val Val Asn Leu Leu Ser Arg Ser Ser Phe Pro Ser Val Asp
1 5 10 15
Ser Tyr Leu Ala Leu Ser Val Leu Val Ala Ile Val Ala Ser Val Thr
20 25 30
Val Phe Thr Thr Phe Arg Ser Gln Pro Glu Leu Gln Lys Leu Ile Glu
35 40 45
Glu Glu Leu Arg Asn Asn Thr Arg Leu Ser Ser Ala Tyr Gly Leu Asn
50 55 60
Ile Glu Ala Leu Ser Gly His Thr Phe Phe Gln Ile Ala His Tyr Ile
65 70 75 80
Leu Ser Asp Thr Thr Leu Ile Trp Val Ala Ile Asn Ser Tyr Phe Ala
85 90 95
Ile Leu Ala Val Cys Thr Arg Leu Ile Ile Lys Leu Thr Phe Lys Glu
100 105 110
Leu Ala Arg Gln Glu Glu Asn Val Ala Arg Gln Ala Phe Phe Cys Tyr
115 120 125
Val Leu Leu Thr Ile Val Tyr Leu Ser Val Val Ile Gly Pro Gln Lys
130 135 140
Gly His Arg Val Met Pro Trp Met Ile Trp Gly Gly Ile Cys Ala Phe
145 150 155 160
Leu Ser His Leu Gln Phe Ile Thr Cys Gln Arg Leu Lys His Ile Ser
165 170 175
Pro Ser Cys Asp Arg Gly Ser Gln Lys Ile Ser Phe Leu Ser Leu Phe
180 185 190
Leu Phe Phe Val Ser Ile Ala Met Thr Phe Leu Ile Ser Arg Phe Gln
195 200 205
His His Leu Thr Trp Gln Pro Ala Val Leu Leu Tyr Phe Asp Cys Leu
210 215 220
Leu Ala Val Phe Arg Ser Thr Tyr Ile Leu Phe Arg Cys Ile Ser Ser
225 230 235 240
Ser Arg Val Phe Ser Phe Asn Pro Asp Ser Val Arg His Phe Asn Tyr
245 250 255
Trp Leu Glu Leu Ile Thr Asn Phe Val Cys Glu Leu Ile Gln Met Leu
260 265 270
Ser Phe Ala Gln Leu Leu Ala Phe Ser Pro Gly Leu Asn Leu Thr Ser
275 280 285
Ile Phe Phe Leu Tyr His Met Lys Leu Thr Tyr Asn Cys Met Thr Glu
290 295 300
Gln Leu Ser Arg His Arg Asn His Lys Lys Ile Phe Glu His Ile Glu
305 310 315 320
Arg Ser Tyr Pro Ser Val Lys Cys Ala Asn Gly Asp Asp Arg Cys Val
325 330 335
Val Cys Trp Glu Leu Leu Gly Thr Ser Arg Arg Leu Pro Cys Ser His
340 345 350
Gln Phe His Asp Trp Cys Leu Met Trp Trp Leu Ala Gln Asp Ser Ser
355 360 365
Cys Pro Thr Cys Arg Cys Thr Ile Pro Ser Pro Gln Asp Gln Ile Arg
370 375 380
Gln Pro Pro Glu Val Gly Asn Ser Thr Arg Leu Arg Phe Asn Gly Gly
385 390 395 400
Ser Phe Gly Phe Val His Phe Pro Ala Phe Thr Leu Glu Val Ala Ala
405 410 415
Asn Phe Gly Pro Phe Phe Gly Arg Ala Ala Glu Pro Thr Glu Glu Gln
420 425 430
Leu Gln Thr Met Leu Glu Gln Val Arg Glu Met Phe Pro Gln Met Ser
435 440 445
Val Asp Ile Ile Met Thr Asp Leu Arg Gln Ser Gly Ser Ala Gln Ser
450 455 460
Thr Ile Glu Asn Ile Leu Glu Gly Arg Ile Gly Met Asn Ala Ser Phe
465 470 475 480
Met Pro Gly Gly Val Leu Asp Asp Glu Leu Ser Asp Glu Ser Glu Asn
485 490 495
Glu Ile Glu Tyr Glu Glu Pro Ala Glu Ile Val Gln Glu Pro Asp Asn
500 505 510
Gly Arg Gln Arg Thr Trp Thr Lys Leu Ser Ser Ser Ser Gly Asp Glu
515 520 525
Asp Leu Ser Tyr Tyr Glu Ile Gln Arg Ala Lys Met Ile Glu Thr Tyr
530 535 540
Arg Arg Lys Tyr Leu Glu Ser Asp Lys Ala Ala Asp Leu Arg Ala Met
545 550 555 560
Gly Ile Thr Glu
<210>19
<211>1932
<212>DNA
<213>人
<220>
<221>CDS
<222>(1)..(1932)
<400>19
atg ccg ctg ctc ttc ctc gag cgc ttc ccc tgg ccc agc ctc cgc acc 48
Met Pro Leu Leu Phe Leu Glu Arg Phe Pro Trp Pro Ser Leu Arg Thr
1 5 10 15
tac acg ggc ctc agc ggc ctg gcc ctg ctg ggc acc atc atc agc gcc 96
Tyr Thr Gly Leu Ser Gly Leu Ala Leu Leu Gly Thr Ile Ile Ser Ala
20 25 30
tac cgc gcg ctc agc cag ccc gag gcc ggc ccc ggc gag ccg gac cag 144
Tyr Arg Ala Leu Ser Gln Pro Glu Ala Gly Pro Gly Glu Pro Asp Gln
35 40 45
cta acg gcc tcg ctg cag cct gag ccg ccg gcg ccc gcc cgg ccg agc 192
Leu Thr Ala Ser Leu Gln Pro Glu Pro Pro Ala Pro Ala Arg Pro Ser
50 55 60
gcc ggg gga ccc cgg gcc cgc gat gtg gcc cag tac ctg ctc tca gac 240
Ala Gly Gly Pro Arg Ala Arg Asp Val Ala Gln Tyr Leu Leu Ser Asp
65 70 75 80
agc ctc ttc gtg tgg gtt cta gta aat acc gct tgc tgt gtt ttg atg 288
Ser Leu Phe Val Trp Val Leu Val Asn Thr Ala Cys Cys Val Leu Met
85 90 95
ttg gtg gct aag ctc atc cag tgt att gtg ttt ggc cct ctt cga gtg 336
Leu Val Ala Lys Leu Ile Gln Cys Ile Val Phe Gly Pro Leu Arg Val
100 105 110
agt gag aga cag cat ctc aaa gac aaa ttt tgg aat ttt att ttc tac 384
Ser Glu Arg Gln His Leu Lys Asp Lys Phe Trp Asn Phe Ile Phe Tyr
115 120 125
aag ttc att ttc atc ttt ggt gtg ctg aat gtc cag aca gtg gaa gag 432
Lys Phe Ile Phe Ile Phe Gly Val Leu Asn Val Gln Thr Val Glu Glu
130 135 140
gtg gtc atg tgg tgc ctc tgg ttt gcc gga ctt gtc ttt ctg cac ctg 480
Val Val Met Trp Cys Leu Trp Phe Ala Gly Leu Val Phe Leu His Leu
145 150 155 160
atg gtt cag ctc tgc aag gat cga ttt gaa tat ctt tcc ttc tcg ccc 528
Met Val Gln Leu Cys Lys Asp Arg Phe Glu Tyr Leu Ser Phe Ser Pro
165 170 175
acc acg ccg atg agc agc cac ggt cga gtc ctg tcc ctg ttg gtt gcc 576
Thr Thr Pro Met Ser Ser His Gly Arg Val Leu Ser Leu Leu Val Ala
180 185 190
atg ctg ctt tcc tgc tgt gga ctg gcg gcc gtc tgc tcc atc acc ggc 624
Met Leu Leu Ser Cys Cys Gly Leu Ala Ala Val Cys Ser Ile Thr Gly
195 200 205
tac acc cac gga atg cac acc ttg gct ttc atg gct gca gag tct ctt 672
Tyr Thr His Gly Met His Thr Leu Ala Phe Met Ala Ala Glu Ser Leu
210 215 220
ctt gtg aca gtg agg act gct cat gtg att tta cga tac gta att cac 720
Leu Val Thr Val Arg Thr Ala His Val Ile Leu Arg Tyr Val Ile His
225 230 235 240
ctc tgg gac ctc aac cac gaa ggg acg tgg gaa gga aag ggg acg tat 768
Leu Trp Asp Leu Asn His Glu Gly Thr Trp Glu Gly Lys Gly Thr Tyr
245 250 255
gtc tat tac aca gac ttt gtc atg gag ctc act ctc ctg tcc ctg gac 816
Val Tyr Tyr Thr Asp Phe Val Met Glu Leu Thr Leu Leu Ser Leu Asp
260 265 270
ctc atg cac cat att cac atg ttg tta ttt ggc aac atc tgg tta tcc 864
Leu Met His His Ile His Met Leu Leu Phe Gly Asn Ile Trp Leu Ser
275 280 285
atg gcc agc ctg gtc atc ttt atg cag ctg cgt tac ctg ttt cat gag 912
Met Ala Ser Leu Val Ile Phe Met Gln Leu Arg Tyr Leu Phe His Glu
290 295 300
gtg caa cgt cga att cgt cgg cac aag aac tat cta cgt gtg gtt gga 960
Val Gln Arg Arg Ile Arg Arg His Lys Asn Tyr Leu Arg Val Val Gly
305 310 315 320
aac atg gag gcc agg ttt gca gtt gca act cca gag gag ctg gct gtc 1008
Asn Met Glu Ala Arg Phe Ala Val Ala Thr Pro Glu Glu Leu Ala Val
325 330 335
aac aat gac gac tgt gcc atc tgt tgg gac tcc atg cag gct gcg cgg 1056
Asn Asn Asp Asp Cys Ala Ile Cys Trp Asp Ser Met Gln Ala Ala Arg
340 345 350
aaa ctg ccc tgt gga cat ctt ttc cac aac tcc tgt ctt cgt tcc tgg 1104
Lys Leu Pro Cys Gly His Leu Phe His Asn Ser Cys Leu Arg Ser Trp
355 360 365
cta gaa caa gac acc tcc tgt cca aca tgc aga atg tct ctt aat att 1152
Leu Glu Gln Asp Thr Ser Cys Pro Thr Cys Arg Met Ser Leu Asn Ile
370 375 380
gcc gac aat aat cgt gtc agg gaa gaa cat caa gga gag aac ttg gat 1200
Ala Asp Asn Asn Arg Val Arg Glu Glu His Gln Gly Glu Asn Leu Asp
385 390 395 400
gag aat ttg gtt cct gta gca gca gcc gaa ggg aga cct cgc tta aac 1248
Glu Asn Leu Val Pro Val Ala Ala Ala Glu Gly Arg Pro Arg Leu Asn
405 410 415
caa cac aat cac ttc ttc cat ttc gat ggg tct cgg att gcg agc tgg 1296
Gln His Asn His Phe Phe His Phe Asp Gly Ser Arg Ile Ala Ser Trp
420 425 430
ctg ccg agt ttt tcg gtt gaa gtg atg cac acc acc aac att ctt ggc 1344
Leu Pro Ser Phe Ser Val Glu Val Met His Thr Thr Asn Ile Leu Gly
435 440 445
att acg cag gcc agc aac tcc cag ctc aat gca atg gct cat cag att 1392
Ile Thr Gln Ala Ser Asn Ser Gln Leu Asn Ala Met Ala His Gln Ile
450 455 460
caa gag atg ttt ccc cag gtt cca tac cat ctg gta ctg cag gac ctc 1440
Gln Glu Met Phe Pro Gln Val Pro Tyr His Leu Val Leu Gln Asp Leu
465 470 475 480
cag ctg aca cgc tca gtt gaa ata aca aca gac aat att tta gaa gga 1488
Gln Leu Thr Arg Ser Val Glu Ile Thr Thr Asp Asn Ile Leu Glu Gly
485 490 495
cgg att caa gta cct ttt cct aca cag cgg tca gat agc atc aga cct 1536
Arg Ile Gln Val Pro Phe Pro Thr Gln Arg Ser Asp Ser Ile Arg Pro
500 505 510
gca ttg aac agt cct gtg gaa agg cca agc agt gac cag gaa gag gga 1584
Ala Leu Asn Ser Pro Val Glu Arg Pro Ser Ser Asp Gln Glu Glu Gly
515 520 525
gaa act tct gct cag acc gag cgt gtg cca ctg gac ctc agt cct cgc 1632
Glu Thr Ser Ala Gln Thr Glu Arg Val Pro Leu Asp Leu Ser Pro Arg
530 535 540
ctg gag gag acg ctg gac ttc ggc gag gtg gaa gtg gag ccc agt gag 1680
Leu Glu Glu Thr Leu Asp Phe Gly Glu Val Glu Val Glu Pro Ser Glu
545 550 555 560
gtg gaa gac ttc gag gct cgt ggg agc cgc ttc tcc aag tct gct gat 1728
Val Glu Asp Phe Glu Ala Arg Gly Ser Arg Phe Ser Lys Ser Ala Asp
565 570 575
gag aga cag cgc atg ctg gtg cag cgt aag gac gaa ctc ctc cag caa 1776
Glu Arg Gln Arg Met Leu Val Gln Arg Lys Asp Glu Leu Leu Gln Gln
580 585 590
gct cgc aaa cgt ttc ttg aac aaa agt tct gaa gat gat gcg gcc tca 1824
Ala Arg Lys Arg Phe Leu Asn Lys Ser Ser Glu Asp Asp Ala Ala Ser
595 600 605
gag agc ttc ctc ccc tcg gaa ggt gcg tcc tct gac ccc gtg acc ctg 1872
Glu Ser Phe Leu Pro Ser Glu Gly Ala Ser Ser Asp Pro Val Thr Leu
610 615 620
cgt cga agg atg ctg gct gcc gcc gcg gaa cgg agg ctt cag aag cag 1920
Arg Arg Arg Met Leu Ala Ala Ala Ala Glu Arg Arg Leu Gln Lys Gln
625 630 635 640
cag acc tcc tag 1932
Gln Thr Ser
<210>20
<211>643
<212>PRT
<213>人
<400>20
Met Pro Leu Leu Phe Leu Glu Arg Phe Pro Trp Pro Ser Leu Arg Thr
1 5 10 15
Tyr Thr Gly Leu Ser Gly Leu Ala Leu Leu Gly Thr Ile Ile Ser Ala
20 25 30
Tyr Arg Ala Leu Ser Gln Pro Glu Ala Gly Pro Gly Glu Pro Asp Gln
35 40 45
Leu Thr Ala Ser Leu Gln Pro Glu Pro Pro Ala Pro Ala Arg Pro Ser
50 55 60
Ala Gly Gly Pro Arg Ala Arg Asp Val Ala Gln Tyr Leu Leu Ser Asp
65 70 75 80
Ser Leu Phe Val Trp Val Leu Val Asn Thr Ala Cys Cys Val Leu Met
85 90 95
Leu Val Ala Lys Leu Ile Gln Cys Ile Val Phe Gly Pro Leu Arg Val
100 105 110
Ser Glu Arg Gln His Leu Lys Asp Lys Phe Trp Asn Phe Ile Phe Tyr
115 120 125
Lys Phe Ile Phe Ile Phe Gly Val Leu Asn Val Gln Thr Val Glu Glu
130 135 140
Val Val Met Trp Cys Leu Trp Phe Ala Gly Leu Val Phe Leu His Leu
145 150 155 160
Met Val Gln Leu Cys Lys Asp Arg Phe Glu Tyr Leu Ser Phe Ser Pro
165 170 175
Thr Thr Pro Met Ser Ser His Gly Arg Val Leu Ser Leu Leu Val Ala
180 185 190
Met Leu Leu Ser Cys Cys Gly Leu Ala Ala Val Cys Ser Ile Thr Gly
195 200 205
Tyr Thr His Gly Met His Thr Leu Ala Phe Met Ala Ala Glu Ser Leu
210 215 220
Leu Val Thr Val Arg Thr Ala His Val Ile Leu Arg Tyr Val Ile His
225 230 235 240
Leu Trp Asp Leu Asn His Glu Gly Thr Trp Glu Gly Lys Gly Thr Tyr
245 250 255
Val Tyr Tyr Thr Asp Phe Val Met Glu Leu Thr Leu Leu Ser Leu Asp
260 265 270
Leu Met His His Ile His Met Leu Leu Phe Gly Asn Ile Trp Leu Ser
275 280 285
Met Ala Ser Leu Val Ile Phe Met Gln Leu Arg Tyr Leu Phe His Glu
290 295 300
Val Gln Arg Arg Ile Arg Arg His Lys Asn Tyr Leu Arg Val Val Gly
305 310 315 320
Asn Met Glu Ala Arg Phe Ala Val Ala Thr Pro Glu Glu Leu Ala Val
325 330 335
Asn Asn Asp Asp Cys Ala Ile Cys Trp Asp Ser Met Gln Ala Ala Arg
340 345 350
Lys Leu Pro Cys Gly His Leu Phe His Asn Ser Cys Leu Arg Ser Trp
355 360 365
Leu Glu Gln Asp Thr Ser Cys Pro Thr Cys Arg Met Ser Leu Asn Ile
370 375 380
Ala Asp Asn Asn Arg Val Arg Glu Glu His Gln Gly Glu Asn Leu Asp
385 390 395 400
Glu Asn Leu Val Pro Val Ala Ala Ala Glu Gly Arg Pro Arg Leu Asn
405 410 415
Gln His Asn His Phe Phe His Phe Asp Gly Ser Arg Ile Ala Ser Trp
420 425 430
Leu Pro Ser Phe Ser Val Glu Val Met His Thr Thr Asn Ile Leu Gly
435 440 445
Ile Thr Gln Ala Ser Asn Ser Gln Leu Asn Ala Met Ala His Gln Ile
450 455 460
Gln Glu Met Phe Pro Gln Val Pro Tyr His Leu Val Leu Gln Asp Leu
465 470 475 480
Gln Leu Thr Arg Ser Val Glu Ile Thr Thr Asp Asn Ile Leu Glu Gly
485 490 495
Arg Ile Gln Val Pro Phe Pro Thr Gln Arg Ser Asp Ser Ile Arg Pro
500 505 510
Ala Leu Asn Ser Pro Val Glu Arg Pro Ser Ser Asp Gln Glu Glu Gly
515 520 525
Glu Thr Ser Ala Gln Thr Glu Arg Val Pro Leu Asp Leu Ser Pro Arg
530 535 540
Leu Glu Glu Thr Leu Asp Phe Gly Glu Val Glu Val Glu Pro Ser Glu
545 550 555 560
Val Glu Asp Phe Glu Ala Arg Gly Ser Arg Phe Ser Lys Ser Ala Asp
565 570 575
Glu Arg Gln Arg Met Leu Val Gln Arg Lys Asp Glu Leu Leu Gln Gln
580 585 590
Ala Arg Lys Arg Phe Leu Asn Lys Ser Ser Glu Asp Asp Ala Ala Ser
595 600 605
Glu Ser Phe Leu Pro Ser Glu Gly Ala Ser Ser Asp Pro Val Thr Leu
610 615 620
Arg Arg Arg Met Leu Ala Ala Ala Ala Glu Arg Arg Leu Gln Lys Gln
625 630 635 640
Gln Thr Ser
<210>21
<211>564
<212>DNA
<213>线虫
<220>
<221>CDS
<222>(1)..(564)
<400>21
atg gct caa aaa tcg gct tta atc ata ttg gcg gcc gaa gga gct gag 48
Met Ala Gln Lys Ser Ala Leu Ile Ile Leu Ala Ala Glu Gly Ala Glu
1 5 10 15
gaa atg gag gtc att atc act gga gat gta ctt gct cgt ggt gaa att 96
Glu Met Glu Val Ile Ile Thr Gly Asp Val Leu Ala Arg Gly Glu Ile
20 25 30
cgt gtg gtt tat gcc gga tta gat gga gcc gaa ccg gta aaa tgt gct 144
Arg Val Val Tyr Ala Gly Leu Asp Gly Ala Glu Pro Val Lys Cys Ala
35 40 45
cgc gga gcc cac atc gtg cca gac gtc aaa ctc gaa gac gtg gaa acc 192
Arg Gly Ala His Ile Val Pro Asp Val Lys Leu Glu Asp Val Glu Thr
50 55 60
gaa aaa ttc gat att gtg att ctt cca ggc ggc caa ccg ggc agc aac 240
Glu Lys Phe Asp Ile Val Ile Leu Pro Gly Gly Gln Pro Gly Ser Asn
65 70 75 80
acg ttg gct gaa agc cta ctt gtc cgc gat gtt ctc aag agc caa gta 288
Thr Leu Ala Glu Ser Leu Leu Val Arg Asp Val Leu Lys Ser Gln Val
85 90 95
gag tct ggt ggg ctg att gga gca att tgt gca gct cca att gca ctc 336
Glu Ser Gly Gly Leu Ile Gly Ala Ile Cys Ala Ala Pro Ile Ala Leu
l00 105 110
ttg agc cat gga gtc aag gca gaa ctt gtg aca agt cat cca agt gtt 384
Leu Ser His Gly Val Lys Ala Glu Leu Val Thr Ser His Pro Ser Val
115 120 125
aag gag aaa ctc gag aaa gga ggc tac aag tac tcg gag gat cgt gtt 432
Lys Glu Lys Leu Glu Lys Gly Gly Tyr Lys Tyr Ser Glu Asp Arg Val
130 135 140
gtt gtc agt ggc aaa atc atc acc tct cgt gga ccc gga act gcc ttc 480
Val Val Ser Gly Lys Ile Ile Thr Ser Arg Gly Pro Gly Thr Ala Phe
145 150 155 160
gaa ttt gcg ctg aaa att gtg gag ctg ctt gag gga aag gac aag gcc 528
Glu Phe Ala Leu Lys Ile Val Glu Leu Leu Glu Gly Lys Asp Lys Ala
165 170 175
acc agc ctt att gct ccg atg ctc ctg aag ctc taa 564
Thr Ser Leu Ile Ala Pro Met Leu Leu Lys Leu
180 185
<210>22
<211>187
<212>PRT
<213>线虫
<400>22
Met Ala Gln Lys Ser Ala Leu Ile Ile Leu Ala Ala Glu Gly Ala Glu
1 5 10 15
Glu Met Glu Val Ile Ile Thr Gly Asp Val Leu Ala Arg Gly Glu Ile
20 25 30
Arg Val Val Tyr Ala Gly Leu Asp Gly Ala Glu Pro Val Lys Cys Ala
35 40 45
Arg Gly Ala His Ile Val Pro Asp Val Lys Leu Glu Asp Val Glu Thr
50 55 60
Glu Lys Phe Asp Ile Val Ile Leu Pro Gly Gly Gln Pro Gly Ser Asn
65 70 75 80
Thr Leu Ala Glu Ser Leu Leu Val Arg Asp Val Leu Lys Ser Gln Val
85 90 95
Glu Ser Gly Gly Leu Ile Gly Ala Ile Cys Ala Ala Pro Ile Ala Leu
100 105 110
Leu Ser His Gly Val Lys Ala Glu Leu Val Thr Ser His Pro Ser Val
115 120 125
Lys Glu Lys Leu Glu Lys Gly Gly Tyr Lys Tyr Ser Glu Asp Arg Val
130 135 140
Val Val Ser Gly Lys Ile Ile Thr Ser Arg Gly Pro Gly Thr Ala Phe
145 150 155 160
Glu Phe Ala Leu Lys Ile Val Glu Leu Leu Glu Gly Lys Asp Lys Ala
165 170 175
Thr Ser Leu Ile Ala Pro Met Leu Leu Lys Leu
180 185
<210>23
<211>570
<212>DNA
<213>人
<220>
<221>CDS
<222>(1)..(570)
<400>23
atg gct tcc aaa aga gct ctg gtc atc ctg gct aaa gga gca gag gaa 48
Met Ala Ser Lys Arg Ala Leu Val Ile Leu Ala Lys Gly Ala Glu Glu
1 5 10 15
atg gag acg gtc atc cct gta gat gtc atg agg cga gct ggg att aag 96
Met Glu Thr Val Ile Pro Val Asp Val Met Arg Arg Ala Gly Ile Lys
20 25 30
gtc acc gtt gca ggc ctg gct gga aaa gac cca gta cag tgt agc cgt 144
Val Thr Val Ala Gly Leu Ala Gly Lys Asp Pro Val Gln Cys Ser Arg
35 40 45
gat gtg gtc att tgt cct gat gcc agc ctt gaa gat gca aaa aaa gag 192
Asp Val Val Ile Cys Pro Asp Ala Ser Leu Glu Asp Ala Lys Lys Glu
50 55 60
gga cca tat gat gtg gtg gtt cta cca gga ggt aat ctg ggc gca cag 240
Gly Pro Tyr Asp Val Val Val Leu Pro Gly Gly Asn Leu Gly Ala Gln
65 70 75 80
aat tta tct gag tct gct gct gtg aag gag ata ctg aag gag cag gaa 288
Asn Leu Ser Glu Ser Ala Ala Val Lys Glu Ile Leu Lys Glu Gln Glu
85 90 95
aac cgg aag ggc ctg ata gcc gcc atc tgt gca ggt cct act gct ctg 336
Asn Arg Lys Gly Leu Ile Ala Ala Ile Cys Ala Gly Pro Thr Ala Leu
100 105 110
ttg gct cat gaa ata ggt ttt gga agt aaa gtt aca aca cac cct ctt 384
Leu Ala His Glu Ile Gly Phe Gly Ser Lys Val Thr Thr His Pro Leu
115 120 125
gct aaa gac aaa atg atg aat gga ggt cat tac acc tac tct gag aat 432
Ala Lys Asp Lys Met Met Asn Gly Gly His Tyr Thr Tyr Ser Glu Asn
130 135 140
cgt gtg gaa aaa gac ggc ctg att ctt aca agc cgg ggg cct ggg acc 480
Arg Val Glu Lys Asp Gly Leu Ile Leu Thr Ser Arg Gly Pro Gly Thr
145 150 155 160
agc ttc gag ttt gcg ctt gca att gtt gaa gcc ctg aat ggc aag gag 528
Ser Phe Glu Phe Ala Leu Ala Ile Val Glu Ala Leu Asn Gly Lys Glu
165 170 175
gtg gcg gct caa gtg aag gct cca ctt gtt ctt aaa gac tag 570
Val Ala Ala Gln Val Lys Ala Pro Leu Val Leu Lys Asp
180 185
<210>24
<211>189
<212>PRT
<213>人
<400>24
Met Ala Ser Lys Arg Ala Leu Val Ile Leu Ala Lys Gly Ala Glu Glu
1 5 10 15
Met Glu Thr Val Ile Pro Val Asp Val Met Arg Arg Ala Gly Ile Lys
20 25 30
Val Thr Val Ala Gly Leu Ala Gly Lys Asp Pro Val Gln Cys Ser Arg
35 40 45
Asp Val Val Ile Cys Pro Asp Ala Ser Leu Glu Asp Ala Lys Lys Glu
50 55 60
Gly Pro Tyr Asp Val Val Val Leu Pro Gly Gly Asn Leu Gly Ala Gln
65 70 75 80
Asn Leu Ser Glu Ser Ala Ala Val Lys Glu Ile Leu Lys Glu Gln Glu
85 90 95
Asn Arg Lys Gly Leu Ile Ala Ala Ile Cys Ala Gly Pro Thr Ala Leu
100 105 110
Leu Ala His Glu Ile Gly Phe Gly Ser Lys Val Thr Thr His Pro Leu
115 120 125
Ala Lys Asp Lys Met Met Asn Gly Gly His Tyr Thr Tyr Ser Glu Asn
130 135 140
Arg Val Glu Lys Asp Gly Leu Ile Leu Thr Ser Arg Gly Pro Gly Thr
145 150 155 160
Ser Phe Glu Phe Ala Leu Ala Ile Val Glu Ala Leu Asn Gly Lys Glu
165 170 175
Val Ala Ala Gln Val Lys Ala Pro Leu Val Leu Lys Asp
180 185
<210>25
<211>1926
<212>DNA
<213>线虫
<220>
<221>CDS
<222>(1)..(1926)
<400>25
atg tct atg aaa cga ttc gga aaa gca gca tat cga atc gca aat gag 48
Met Ser Met Lys Arg Phe Gly Lys Ala Ala Tyr Arg Ile Ala Asn Glu
1 5 10 15
tta gtt gca aaa ggt gga cga cta cca att ttc caa cgc ttc ctg ccg 96
Leu Val Ala Lys Gly Gly Arg Leu Pro Ile Phe Gln Arg Phe Leu Pro
20 25 30
aga ata ttt ccc gcc act tat aat tta gga gtt cat gtc gta ctc aaa 144
Arg Ile Phe Pro Ala Thr Tyr Asn Leu Gly Val His Val Val Leu Lys
35 40 45
aag gct cca ttt cca cga caa aat gct cta cga att gct cgc ctt gta 192
Lys Ala Pro Phe Pro Arg Gln Asn Ala Leu Arg Ile Ala Arg Leu Val
50 55 60
act cgc cac ggt cga gtt ttc cgg cca ttt tcc tca gta ata atc gaa 240
Thr Arg His Gly Arg Val Phe Arg Pro Phe Ser Ser Val Ile Ile Glu
65 70 75 80
aga cat cga ttt caa aat caa aat gat tgg cgt cga aag ttt caa ccg 288
Arg His Arg Phe Gln Asn Gln Asn Asp Trp Arg Arg Lys Phe Gln Pro
85 90 95
att cgt aaa gaa ttg cca aga aat gtg gat tta gtc gaa cga atc agg 336
Ile Arg Lys Glu Leu Pro Arg Asn Val Asp Leu Val Glu Arg Ile Arg
100 105 110
cag ata ttt ggc aat tct cta cga tac aat gag gat ttg aaa agc act 384
Gln Ile Phe Gly Asn Ser Leu Arg Tyr Asn Glu Asp Leu Lys Ser Thr
115 120 125
gaa tgg ccg aat aga att gat tct tat gag ttt ggg gaa ttt ctc ggt 432
Glu Trp Pro Asn Arg Ile Asp Ser Tyr Glu Phe Gly Glu Phe Leu Gly
130 135 140
caa gga tgc aat gca gca gtt tac tct gcg aga tta gcc aat tct gat 480
Gln Gly Cys Asn Ala Ala Val Tyr Ser Ala Arg Leu Ala Asn Ser Asp
145 150 155 160
gca gaa tcc tca ggg aat act cac tat ggt gca ggg ttt aat gaa gtc 528
Ala Glu Ser Ser Gly Asn Thr His Tyr Gly Ala Gly Phe Asn Glu Val
165 170 175
aca aat ata ctt gca gaa att ccg cca gtt agc aaa gtt gca caa aag 576
Thr Asn Ile Leu Ala Glu Ile Pro Pro Val Ser Lys Val Ala Gln Lys
180 185 190
aaa ttc ccg ttg gca atc aaa tta atg ttt aat ttt gaa cat gat cgc 624
Lys Phe Pro Leu Ala Ile Lys Leu Met Phe Asn Phe Glu His Asp Arg
195 200 205
gat gga gat gct cat ctc ttg aaa tca atg gga aat gaa ttg gct cca 672
Asp Gly Asp Ala His Leu Leu Lys Ser Met Gly Asn Glu Leu Ala Pro
210 215 220
tat ccg aat gct gca aag ttg ctc aat gga caa atg gga aca ttt aga 720
Tyr Pro Asn Ala Ala Lys Leu Leu Asn Gly Gln Met Gly Thr Phe Arg
225 230 235 240
cct ctt cca gca aaa cat cca aat gtt gtt cga att cag aca gct ttt 768
Pro Leu Pro Ala Lys His Pro Asn Val Val Arg Ile Gln Thr Ala Phe
245 250 255
att gat tcg tta aaa gtt ttg cca gat gcg att gaa cga tat cca gat 816
Ile Asp Ser Leu Lys Val Leu Pro Asp Ala Ile Glu Arg Tyr Pro Asp
260 265 270
gcc ctt cac act gca cgt tgg tat gag tca att gcc tcc gaa ccg aaa 864
Ala Leu His Thr Ala Arg Trp Tyr Glu Ser Ile Ala Ser Glu Pro Lys
275 280 285
aca atg tac gta gta atg aga cga tac cga caa aca ctt cat gaa tat 912
Thr Met Tyr Val Val Met Arg Arg Tyr Arg Gln Thr Leu His Glu Tyr
290 295 300
gta tgg act cgt cat cga aat tat tgg aca gga cga gtg ata att gct 960
Val Trp Thr Arg His Arg Asn Tyr Trp Thr Gly Arg Val Ile Ile Ala
305 310 315 320
caa cta tta gaa gca tgt aca tat ctt cat aag cat aaa gtt gct cag 1008
Gln Leu Leu Glu Ala Cys Thr Tyr Leu His Lys His Lys Val Ala Gln
325 330 335
cga gac atg aaa agt gat aat att ctt ctg gaa tat gat ttt gac gac 1056
Arg Asp Met Lys Ser Asp Asn Ile Leu Leu Glu Tyr Asp Phe Asp Asp
340 345 350
gag att ccc caa tta gtt gtc gcc gat ttt gga tgt gca ctt gca tgt 1104
Glu Ile Pro Gln Leu Val Val Ala Asp Phe Gly Cys Ala Leu Ala Cys
355 360 365
gac aat tgg caa gta gac tat gaa tca gat gaa gtt agt ctt gga gga 1152
Asp Asn Trp Gln Val Asp Tyr Glu Ser Asp Glu Val Ser Leu Gly Gly
370 375 380
aat gcc aag aca aaa gca cca gaa att gcg acg gct gtt cct gga aag 1200
Asn Ala Lys Thr Lys Ala Pro Glu Ile Ala Thr Ala Val Pro Gly Lys
385 390 395 400
aat gta aaa gta aac ttc gaa atg gca gat aca tgg gca gct gga ggc 1248
Asn Val Lys Val Asn Phe Glu Met Ala Asp Thr Trp Ala Ala Gly Gly
405 410 415
ctt tct tat gaa gtt cta aca cga tca aat cca ttc tac aaa ctt ctt 1296
Leu Ser Tyr Glu Val Leu Thr Arg Ser Asn Pro Phe Tyr Lys Leu Leu
420 425 430
gat act gca aca tac cag gaa tca gaa cta cca gca ctc cca tct cgt 1344
Asp Thr Ala Thr Tyr Gln Glu Ser Glu Leu Pro Ala Leu Pro Ser Arg
435 440 445
gtc aat ttt gtg gca cga gat gtc att ttt gac cta ctc aag cga gat 1392
Val Asn Phe Val Ala Arg Asp Val Ile Phe Asp Leu Leu Lys Arg Asp
450 455 460
cct aat gaa aga gtc aag ccg aat att gct gca aat gcg ttg aat ttg 1440
Pro Asn Glu Arg Val Lys Pro Asn Ile Ala Ala Asn Ala Leu Asn Leu
465 470 475 480
tca ttg ttc aga atg gga gaa gat gtg aag cag atg atg gaa aaa tgt 1488
Ser Leu Phe Arg Met Gly Glu Asp Val Lys Gln Met Met Glu Lys Cys
485 490 495
gga ata tct caa atg act act cta ttg gct gga agt tct aaa gtt ttg 1536
Gly Ile Ser Gln Met Thr Thr Leu Leu Ala Gly Ser Ser Lys Val Leu
500 505 510
agt caa aaa atc aat agt cgt ctg gac aaa gtg atg aat ctg att act 1584
Ser Gln Lys Ile Asn Ser Arg Leu Asp Lys Val Met Asn Leu Ile Thr
515 520 525
gct gaa act atc atg gcc aac cta gct cca cat ttg att agt cga gca 1632
Ala Glu Thr Ile Met Ala Asn Leu Ala Pro His Leu Ile Ser Arg Ala
530 535 540
gaa cga caa ctt cga gca aca ttt ctt tca aga atg aat cga gaa gat 1680
Glu Arg Gln Leu Arg Ala Thr Phe Leu Ser Arg Met Asn Arg Glu Asp
545 550 555 560
att tgg aga agt ctt caa tat ttc ttc cca gct ggt gtt caa ctt gac 1728
Ile Trp Arg Ser Leu Gln Tyr Phe Phe Pro Ala Gly Val Gln Leu Asp
565 570 575
aca cct gcc aca tca tca gac tgt ttg gag act att tcc agt ttg atg 1776
Thr Pro Ala Thr Ser Ser Asp Cys Leu Glu Thr Ile Ser Ser Leu Met
580 585 590
tcg agt ttt tca aat gat tca gaa aat tac gag aag caa cag aaa ccg 1824
Ser Ser Phe Ser Asn Asp Ser Glu Asn Tyr Glu Lys Gln Gln Lys Pro
595 600 605
gct aaa aat gga tac aac aat gtt cca ctt ctt ctc aga aat gtt atc 1872
Ala Lys Asn Gly Tyr Asn Asn Val Pro Leu Leu Leu Arg Asn Val Ile
610 615 620
cgt aca gat gcg gat gga atc aat gga att gta cat aga gtt cga tct 1920
Arg Thr Asp Ala Asp Gly Ile Asn Gly Ile Val His Arg Val Arg Ser
625 630 635 640
aaa tag 1926
Lys
<210>26
<211>641
<212>PRT
<213>线虫
<400>26
Met Ser Met Lys Arg Phe Gly Lys Ala Ala Tyr Arg Ile Ala Asn Glu
1 5 10 15
Leu Val Ala Lys Gly Gly Arg Leu Pro Ile Phe Gln Arg Phe Leu Pro
20 25 30
Arg Ile Phe Pro Ala Thr Tyr Asn Leu Gly Val His Val Val Leu Lys
35 40 45
Lys Ala Pro Phe Pro Arg Gln Asn Ala Leu Arg Ile Ala Arg Leu Val
50 55 60
Thr Arg His Gly Arg Val Phe Arg Pro Phe Ser Ser Val Ile Ile Glu
65 70 75 80
Arg His Arg Phe Gln Asn Gln Asn Asp Trp Arg Arg Lys Phe Gln Pro
85 90 95
Ile Arg Lys Glu Leu Pro Arg Asn Val Asp Leu Val Glu Arg Ile Arg
100 105 110
Gln Ile Phe Gly Asn Ser Leu Arg Tyr Asn Glu Asp Leu Lys Ser Thr
115 120 125
Glu Trp Pro Asn Arg Ile Asp Ser Tyr Glu Phe Gly Glu Phe Leu Gly
130 135 140
Gln Gly Cys Asn Ala Ala Val Tyr Ser Ala Arg Leu Ala Asn Ser Asp
145 150 155 160
Ala Glu Ser Ser Gly Asn Thr His Tyr Gly Ala Gly Phe Asn Glu Val
165 170 175
Thr Asn Ile Leu Ala Glu Ile Pro Pro Val Ser Lys Val Ala Gln Lys
180 185 190
Lys Phe Pro Leu Ala Ile Lys Leu Met Phe Asn Phe Glu His Asp Arg
195 200 205
Asp Gly Asp Ala His Leu Leu Lys Ser Met Gly Asn Glu Leu Ala Pro
210 215 220
Tyr Pro Asn Ala Ala Lys Leu Leu Asn Gly Gln Met Gly Thr Phe Arg
225 230 235 240
Pro Leu Pro Ala Lys His Pro Asn Val Val Arg Ile Gln Thr Ala Phe
245 250 255
Ile Asp Ser Leu Lys Val Leu Pro Asp Ala Ile Glu Arg Tyr Pro Asp
260 265 270
Ala Leu His Thr Ala Arg Trp Tyr Glu Ser Ile Ala Ser Glu Pro Lys
275 280 285
Thr Met Tyr Val Val Met Arg Arg Tyr Arg Gln Thr Leu His Glu Tyr
290 295 300
Val Trp Thr Arg His Arg Asn Tyr Trp Thr Gly Arg Val Ile Ile Ala
305 310 315 320
Gln Leu Leu Glu Ala Cys Thr Tyr Leu His Lys His Lys Val Ala Gln
325 330 335
Arg Asp Met Lys Ser Asp Asn Ile Leu Leu Glu Tyr Asp Phe Asp Asp
340 345 350
Glu Ile Pro Gln Leu Val Val Ala Asp Phe Gly Cys Ala Leu Ala Cys
355 360 365
Asp Asn Trp Gln Val Asp Tyr Glu Ser Asp Glu Val Ser Leu Gly Gly
370 375 380
Asn Ala Lys Thr Lys Ala Pro Glu Ile Ala Thr Ala Val Pro Gly Lys
385 390 395 400
Asn Val Lys Val Asn Phe Glu Met Ala Asp Thr Trp Ala Ala Gly Gly
405 410 415
Leu Ser Tyr Glu Val Leu Thr Arg Ser Asn Pro Phe Tyr Lys Leu Leu
420 425 430
Asp Thr Ala Thr Tyr Gln Glu Ser Glu Leu Pro Ala Leu Pro Ser Arg
435 440 445
Val Asn Phe Val Ala Arg Asp Val Ile Phe Asp Leu Leu Lys Arg Asp
450 455 460
Pro Asn Glu Arg Val Lys Pro Asn Ile Ala Ala Asn Ala Leu Asn Leu
465 470 475 480
Ser Leu Phe Arg Met Gly Glu Asp Val Lys Gln Met Met Glu Lys Cys
485 490 495
Gly Ile Ser Gln Met Thr Thr Leu Leu Ala Gly Ser Ser Lys Val Leu
500 505 510
Ser Gln Lys Ile Asn Ser Arg Leu Asp Lys Val Met Asn Leu Ile Thr
515 520 525
Ala Glu Thr Ile Met Ala Asn Leu Ala Pro His Leu Ile Ser Arg Ala
530 535 540
Glu Arg Gln Leu Arg Ala Thr Phe Leu Ser Arg Met Asn Arg Glu Asp
545 550 555 560
Ile Trp Arg Ser Leu Gln Tyr Phe Phe Pro Ala Gly Val Gln Leu Asp
565 570 575
Thr Pro Ala Thr Ser Ser Asp Cys Leu Glu Thr Ile Ser Ser Leu Met
580 585 590
Ser Ser Phe Ser Asn Asp Ser Glu Asn Tyr Glu Lys Gln Gln Lys Pro
595 600 605
Ala Lys Asn Gly Tyr Asn Asn Val Pro Leu Leu Leu Arg Asn Val Ile
610 615 620
Arg Thr Asp Ala Asp Gly Ile Asn Gly Ile Val His Arg Val Arg Ser
625 630 635 640
Lys
<210>27
<211>1746
<212>DNA
<213>人
<220>
<221>CDS
<222>(1)..(1746)
<400>27
atg gcg gtg cga cag gcg ctg ggc cgc ggc ctg cag ctg ggt cga gcg 48
Met Ala Val Arg Gln Ala Leu Gly Arg Gly Leu Gln Leu Gly Arg Ala
1 5 10 15
ctg ctg ctg cgc ttc acg ggc aag ccc ggc cgg gcc tac ggc ttg ggg 96
Leu Leu Leu Arg Phe Thr Gly Lys Pro Gly Arg Ala Tyr Gly Leu Gly
20 25 30
cgg ccg ggc ccg gcg gcg ggc tgt gtc cgc ggg gag cgt cca ggc tgg 144
Arg Pro Gly Pro Ala Ala Gly Cys Val Arg Gly Glu Arg Pro Gly Trp
35 40 45
gcc gca gga ccg ggc gcg gag cct cgc agg gtc ggg ctc ggg ctc cct 192
Ala Ala Gly Pro Gly Ala Glu Pro Arg Arg Val Gly Leu Gly Leu Pro
50 55 60
aac cgt ctc cgc ttc ttc cgc cag tcg gtg gcc ggg ctg gcg gcg cgg 240
Asn Arg Leu Arg Phe Phe Arg Gln Ser Val Ala Gly Leu Ala Ala Arg
65 70 75 80
ttg cag cgg cag ttc gtg gtg cgg gcc tgg ggc tgc gcg ggc cct tgc 288
Leu Gln Arg Gln Phe Val Val Arg Ala Trp Gly Cys Ala Gly Pro Cys
85 90 95
ggc cgg gca gtc ttt ctg gcc ttc ggg cta ggg ctg ggc ctc atc gag 336
Gly Arg Ala Val Phe Leu Ala Phe Gly Leu Gly Leu Gly Leu Ile Glu
100 105 110
gaa aaa cag gcg gag agc cgg cgg gcg gtc tcg gcc tgt cag gag atc 384
Glu Lys Gln Ala Glu Ser Arg Arg Ala Val Ser Ala Cys Gln Glu Ile
115 120 125
cag gca att ttt acc cag aaa agc aag ccg ggg cct gac ccg ttg gac 432
Gln Ala Ile Phe Thr Gln Lys Ser Lys Pro Gly Pro Asp Pro Leu Asp
130 135 140
acg aga cgc ttg cag ggc ttt cgg ctg gag gag tat ctg ata ggg cag 480
Thr Arg Arg Leu Gln Gly Phe Arg Leu Glu Glu Tyr Leu Ile Gly Gln
145 150 155 160
tcc att ggt aag ggc tgc agt gct gct gtg tat gaa gcc acc atg cct 528
Ser Ile Gly Lys Gly Cys Ser Ala Ala Val Tyr Glu Ala Thr Met Pro
165 170 175
aca ttg ccc cag aac ctg gag gtg aca aag agc acc ggg ttg ctt cca 576
Thr Leu Pro Gln Asn Leu Glu Val Thr Lys Ser Thr Gly Leu Leu Pro
180 185 190
ggg aga ggc cca ggt acc agt gca cca gga gaa ggg cag gag cga gct 624
Gly Arg Gly Pro Gly Thr Ser Ala Pro Gly Glu Gly Gln Glu Arg Ala
195 200 205
ccg ggg gcc cct gcc ttc ccc ttg gcc atc aag atg atg tgg aac atc 672
Pro Gly Ala Pro Ala Phe Pro Leu Ala Ile Lys Met Met Trp Asn Ile
210 215 220
tcg gca ggt tcc tcc agc gaa gcc atc ttg aac aca atg agc cag gag 720
Ser Ala Gly Ser Ser Ser Glu Ala Ile Leu Asn Thr Met Ser Gln Glu
225 230 235 240
ctg gtc cca gcg agc cga gtg gcc ttg gct ggg gag tat gga gca gtc 768
Leu Val Pro Ala Ser Arg Val Ala Leu Ala Gly Glu Tyr Gly Ala Val
245 250 255
act tac aga aaa tcc aag aga ggt ccc aag caa cta gcc cct cac ccc 816
Thr Tyr Arg Lys Ser Lys Arg Gly Pro Lys Gln Leu Ala Pro His Pro
260 265 270
aac atc atc cgg gtt ctc cgc gcc ttc acc tct tcc gtg ccg ctg ctg 864
Asn Ile Ile Arg Va1 Leu Arg Ala Phe Thr Ser Ser Val Pro Leu Leu
275 280 285
cca ggg gcc ctg gtc gac tac cct gat gtg ctg ccc tca cgc ctc cac 912
Pro Gly Ala Leu Val Asp Tyr Pro Asp Val Leu Pro Ser Arg Leu His
290 295 300
cct gaa ggc ctg ggc cat ggc cgg acg ctg ttc ctc gtt atg aag aac 960
Pro Glu Gly Leu Gly His Gly Arg Thr Leu Phe Leu Val Met Lys Asn
305 310 315 320
tat ccc tgt acc ctg cgc cag tac ctt tgt gtg aac aca ccc agc ccc 1008
Tyr Pro Cys Thr Leu Arg Gln Tyr Leu Cys Val Asn Thr Pro Ser Pro
325 330 335
cgc ctc gcc gcc atg atg ctg ctg cag ctg ctg gaa ggc gtg gac cat 1056
Arg Leu Ala Ala Met Met Leu Leu Gln Leu Leu Glu Gly Val Asp His
340 345 350
ctg gtt caa cag ggc atc gcg cac aga gac ctg aaa tcc gac aac atc 1104
Leu Val Gln Gln Gly Ile Ala His Arg Asp Leu Lys Ser Asp Asn Ile
355 360 365
ctt gtg gag ctg gac cca gac ggc tgc ccc tgg ctg gtg atc gca gat 1152
Leu Val Glu Leu Asp Pro Asp Gly Cys Pro Trp Leu Val Ile Ala Asp
370 375 380
ttt ggc tgc tgc ctg gct gat gag agc atc ggc ctg cag ttg ccc ttc 1200
Phe Gly Cys Cys Leu Ala Asp Glu Ser Ile Gly Leu Gln Leu Pro Phe
385 390 395 400
agc agc tgg tac gtg gat cgg ggc gga aac ggc tgt ctg atg gcc cca 1248
Ser Ser Trp Tyr Val Asp Arg Gly Gly Asn Gly Cys Leu Met Ala Pro
405 410 415
gag gtg tcc acg gcc cgt cct ggc ccc agg gca gtg att gac tac agc 1296
Glu Val Ser Thr Ala Arg Pro Gly Pro Arg Ala Val Ile Asp Tyr Ser
420 425 430
aag gct gat gcc tgg gca gtg gga gcc atc gcc tat gaa atc ttc ggg 1344
Lys Ala Asp Ala Trp Ala Val Gly Ala Ile Ala Tyr Glu Ile Phe Gly
435 440 445
ctt gtc aat ccc ttc tac ggc cag ggc aag gcc cac ctt gaa agc cgc 1392
Leu Val Asn Pro Phe Tyr Gly Gln Gly Lys Ala His Leu Glu Ser Arg
450 455 460
agc tac caa gag gct cag cta cct gca ctg ccc gag tca gtg cct cca 1440
Ser Tyr Gln Glu Ala Gln Leu Pro Ala Leu Pro Glu Ser Val Pro Pro
465 470 475 480
gac gtg aga cag ttg gtg agg gca ctg ctc cag cga gag gcc agc aag 1488
Asp Val Arg Gln Leu Val Arg Ala Leu Leu Gln Arg Glu Ala Ser Lys
485 490 495
aga cca tct gcc cga gta gcc gca aat gtg ctt cat cta agc ctc tgg 1536
Arg Pro Ser Ala Arg Val Ala Ala Asn Val Leu His Leu Ser Leu Trp
500 505 510
ggt gaa cat att cta gcc ctg aag aat ctg aag tta gac aag atg gtt 1584
Gly Glu His Ile Leu Ala Leu Lys Asn Leu Lys Leu Asp Lys Met Val
515 520 525
ggc tgg ctc ctc caa caa tcg gcc gcc act ttg ttg gcc aac agg ctc 1632
Gly Trp Leu Leu Gln Gln Ser Ala Ala Thr Leu Leu Ala Asn Arg Leu
530 535 540
aca gag aag tgt tgt gtg gaa aca aaa atg aag atg ctc ttt ctg gct 1680
Thr Glu Lys Cys Cys Val Glu Thr Lys Met Lys Met Leu Phe Leu Ala
545 550 555 560
aac ctg gag tgt gaa acg ctc tgc cag gca gcc ctc ctc ctc tgc tca 1728
Asn Leu Glu Cys Glu Thr Leu Cys Gln Ala Ala Leu Leu Leu Cys Ser
565 570 575
tgg agg gca gcc ctg tga 1746
Trp Arg Ala Ala Leu
580
<210>28
<211>581
<212>PRT
<213>人
<400>28
Met Ala Val Arg Gln Ala Leu Gly Arg Gly Leu Gln Leu Gly Arg Ala
1 5 10 15
Leu Leu Leu Arg Phe Thr Gly Lys Pro Gly Arg Ala Tyr Gly Leu Gly
20 25 30
Arg Pro Gly Pro Ala Ala Gly Cys Val Arg Gly Glu Arg Pro Gly Trp
35 40 45
Ala Ala Gly Pro Gly Ala Glu Pro Arg Arg Val Gly Leu Gly Leu Pro
50 55 60
Asn Arg Leu Arg Phe Phe Arg Gln Ser Val Ala Gly Leu Ala Ala Arg
65 70 75 80
Leu Gln Arg Gln Phe Val Val Arg Ala Trp Gly Cys Ala Gly Pro Cys
85 90 95
Gly Arg Ala Val Phe Leu Ala Phe Gly Leu Gly Leu Gly Leu Ile Glu
100 105 110
Glu Lys Gln Ala Glu Ser Arg Arg Ala Val Ser Ala Cys Gln Glu Ile
115 120 125
Gln Ala Ile Phe Thr Gln Lys Ser Lys Pro Gly Pro Asp Pro Leu Asp
130 135 140
Thr Arg Arg Leu Gln Gly Phe Arg Leu Glu Glu Tyr Leu Ile Gly Gln
145 150 155 160
Ser Ile Gly Lys Gly Cys Ser Ala Ala Val Tyr Glu Ala Thr Met Pro
165 170 175
Thr Leu Pro Gln Asn Leu Glu Val Thr Lys Ser Thr Gly Leu Leu Pro
180 185 190
Gly Arg Gly Pro Gly Thr Ser Ala Pro Gly Glu Gly Gln Glu Arg Ala
195 200 205
Pro Gly Ala Pro Ala Phe Pro Leu Ala Ile Lys Met Met Trp Asn Ile
210 215 220
Ser Ala Gly Ser Ser Ser Glu Ala Ile Leu Asn Thr Met Ser Gln Glu
225 230 235 240
Leu Val Pro Ala Ser Arg Val Ala Leu Ala Gly Glu Tyr Gly Ala Val
245 250 255
Thr Tyr Arg Lys Ser Lys Arg Gly Pro Lys Gln Leu Ala Pro His Pro
260 265 270
Asn Ile Ile Arg Val Leu Arg Ala Phe Thr Ser Ser Val Pro Leu Leu
275 280 285
Pro Gly Ala Leu Val Asp Tyr Pro Asp Val Leu Pro Ser Arg Leu His
290 295 300
Pro Glu Gly Leu Gly His Gly Arg Thr Leu Phe Leu Val Met Lys Asn
305 310 315 320
Tyr Pro Cys Thr Leu Arg Gln Tyr Leu Cys Val Asn Thr Pro Ser Pro
325 330 335
Arg Leu Ala Ala Met Met Leu Leu Gln Leu Leu Glu Gly Val Asp His
340 345 350
Leu Val Gln Gln Gly Ile Ala His Arg Asp Leu Lys Ser Asp Asn Ile
355 360 365
Leu Val Glu Leu Asp Pro Asp Gly Cys Pro Trp Leu Val Ile Ala Asp
370 375 380
Phe Gly Cys Cys Leu Ala Asp Glu Ser Ile Gly Leu Gln Leu Pro Phe
385 390 395 400
Ser Ser Trp Tyr Val Asp Arg Gly Gly Asn Gly Cys Leu Met Ala Pro
405 410 415
Glu Val Ser Thr Ala Arg Pro Gly Pro Arg Ala Val Ile Asp Tyr Ser
420 425 430
Lys Ala Asp Ala Trp Ala Val Gly Ala Ile Ala Tyr Glu Ile Phe Gly
435 440 445
Leu Val Asn Pro Phe Tyr Gly Gln Gly Lys Ala His Leu Glu Ser Arg
450 455 460
Ser Tyr Gln Glu Ala Gln Leu Pro Ala Leu Pro Glu Ser Val Pro Pro
465 470 475 480
Asp Val Arg Gln Leu Val Arg Ala Leu Leu Gln Arg Glu Ala Ser Lys
485 490 495
Arg Pro Ser Ala Arg Val Ala Ala Asn Val Leu His Leu Ser Leu Trp
500 505 5l0
Gly Glu His Ile Leu Ala Leu Lys Asn Leu Lys Leu Asp Lys Met Val
515 520 525
Gly Trp Leu Leu Gln Gln Ser Ala Ala Thr Leu Leu Ala Asn Arg Leu
530 535 540
Thr Glu Lys Cys Cys Val Glu Thr Lys Met Lys Met Leu Phe Leu Ala
545 550 555 560
Asn Leu Glu Cys Glu Thr Leu Cys Gln Ala Ala Leu Leu Leu Cys Ser
565 570 575
Trp Arg Ala Ala Leu
580
<210>29
<211>1074
<212>DNA
<213>线虫
<220>
<221>CDS
<222>(1)..(1074)
<400>29
atg caa gga caa gga tca cca ttc tgc cgt tct aga acc cgc tcg aga 48
Met Gln Gly Gln Gly Ser Pro Phe Cys Arg Ser Arg Thr Arg Ser Arg
1 5 10 15
tct cgt gga gct ttc aat cgt agc tcc aac cac ggt tca gtg ctt cca 96
Ser Arg Gly Ala Phe Asn Arg Ser Ser Asn His Gly Ser Val Leu Pro
20 25 30
att cag cct gcc gta ttg gat tca att gcc gag gaa tca tcg tct act 144
Ile Gln Pro Ala Val Leu Asp Ser Ile Ala Glu Glu Ser Ser Ser Thr
35 40 45
atc atg aca gta gtc aat cct ttg atg gtg gca gca aga cag ctc aaa 192
Ile Met Thr Val Val Asn Pro Leu Met Val Ala Ala Arg Gln Leu Lys
50 55 60
ttt gct tgc cag atg gct cat gga agt cca gtt gga atc atc gac aaa 240
Phe Ala Cys Gln Met Ala His Gly Ser Pro Val Gly Ile Ile Asp Lys
65 70 75 80
tgg aac aat atg gag gaa ttg tat caa tca att gcc gat tgc ttt aca 288
Trp Asn Asn Met Glu Glu Leu Tyr Gln Ser Ile Ala Asp Cys Phe Thr
85 90 95
att tca aaa gat gat atc att ttc ctg aca gtc aat gat ttt aag cca 336
Ile Ser Lys Asp Asp Ile Ile Phe Leu Thr Val Asn Asp Phe Lys Pro
100 105 110
gac atg aag aac atg ttc act gga aca ctg aac ttc aag gat atg ctc 384
Asp Met Lys Asn Met Phe Thr Gly Thr Leu Asn Phe Lys Asp Met Leu
115 120 125
ttc gcc cac att cgc gga caa gca acc gag ctc cga gtc gtc aaa gat 432
Phe Ala His Ile Arg Gly Gln Ala Thr Glu Leu Arg Val Val Lys Asp
130 135 140
gct aaa aac ttt gga gtg aca atc acg gac aac gga ctc ggg aat gca 480
Ala Lys Asn Phe Gly Val Thr Ile Thr Asp Asn Gly Leu Gly Asn Ala
145 150 155 160
ttt atc aag gtc ata agc cca gat tcg gtg ttt gat cgt atg cgt cca 528
Phe Ile Lys Val Ile Ser Pro Asp Ser Val Phe Asp Arg Met Arg Pro
165 170 175
gcc act caa gtt ggt caa ctc att gag gcg gtc aat gga gaa tgt gtg 576
Ala Thr Gln Val Gly Gln Leu Ile Glu Ala Val Asn Gly Glu Cys Val
180 185 190
ctc ggg aaa agg cat tac caa gtt gcc cga att ttg aaa aat gtt cgt 624
Leu Gly Lys Arg His Tyr Gln Val Ala Arg Ile Leu Lys Asn Val Arg
195 200 205
cgc ggc gag gaa tgc gtg gtt cga ttg att gct cca aag act gct gat 672
Arg Gly Glu Glu Cys Val Val Arg Leu Ile Ala Pro Lys Thr Ala Asp
210 215 220
cca gga acc atg aag acg act gga aaa act ggc gga ggt ctg gca aaa 720
Pro Gly Thr Met Lys Thr Thr Gly Lys Thr Gly Gly Gly Leu Ala Lys
225 230 235 240
gga acc att cgt ttc aaa tcg gaa ggc gga ttt gct gtt gag gat gtt 768
Gly Thr Ile Arg Phe Lys Ser Glu Gly Gly Phe Ala Val Glu Asp Val
245 250 255
caa gat cag atg atc caa gct gag atg tgc gga aag ctc aat gag ata 816
Gln Asp Gln Met Ile Gln Ala Glu Met Cys Gly Lys Leu Asn Glu Ile
260 265 270
ttc gac caa tac ttg gga gtt caa gat gat cag ctg gcc atg aga atc 864
Phe Asp Gln Tyr Leu Gly Val Gln Asp Asp Gln Leu Ala Met Arg Ile
275 280 285
tgg gaa act gct tca aac tgc gag acg ctt ttg caa ctc agt gaa gcc 912
Trp Glu Thr Ala Ser Asn Cys Glu Thr Leu Leu Gln Leu Ser Glu Ala
290 295 300
atc aaa gag tcg gag ctc tca atg ttc gat ttc ccg gat gga atg gtt 960
Ile Lys Glu Ser Glu Leu Ser Met Phe Asp Phe Pro Asp Gly Met Val
305 310 315 320
ttc gat atg tgg gga atc atc ggt gat ttg aag cgg gag caa cgt gag 1008
Phe Asp Met Trp Gly Ile Ile Gly Asp Leu Lys Arg Glu Gln Arg Glu
325 330 335
aag aag cca tcc cca gtc atg aag aat gcg att tca aga cca tcg gct 1056
Lys Lys Pro Ser Pro Val Met Lys Asn Ala Ile Ser Arg Pro Ser Ala
340 345 350
atg aaa ctc ttt gag taa 1074
Met Lys Leu Phe Glu
355
<210>30
<211>357
<212>PRT
<213>线虫
<400>30
Met Gln Gly Gln Gly Ser Pro Phe Cys Arg Ser Arg Thr Arg Ser Arg
1 5 10 15
Ser Arg Gly Ala Phe Asn Arg Ser Ser Asn His Gly Ser Val Leu Pro
20 25 30
Ile Gln Pro Ala Val Leu Asp Ser Ile Ala Glu Glu Ser Ser Ser Thr
35 40 45
Ile Met Thr Val Val Asn Pro Leu Met Val Ala Ala Arg Gln Leu Lys
50 55 60
Phe Ala Cys Gln Met Ala His Gly Ser Pro Val Gly Ile Ile Asp Lys
65 70 75 80
Trp Asn Asn Met Glu Glu Leu Tyr Gln Ser Ile Ala Asp Cys Phe Thr
85 90 95
Ile Ser Lys Asp Asp Ile Ile Phe Leu Thr Val Asn Asp Phe Lys Pro
100 105 110
Asp Met Lys Asn Met Phe Thr Gly Thr Leu Asn Phe Lys Asp Met Leu
115 120 125
Phe Ala His Ile Arg Gly Gln Ala Thr Glu Leu Arg Val Val Lys Asp
130 135 140
Ala Lys Asn Phe Gly Val Thr Ile Thr Asp Asn Gly Leu Gly Asn Ala
145 150 155 160
Phe Ile Lys Val Ile Ser Pro Asp Ser Val Phe Asp Arg Met Arg Pro
165 170 175
Ala Thr Gln Val Gly Gln Leu Ile Glu Ala Val Asn Gly Glu Cys Val
180 185 190
Leu Gly Lys Arg His Tyr Gln Val Ala Arg Ile Leu Lys Asn Val Arg
195 200 205
Arg Gly Glu Glu Cys Val Val Arg Leu Ile Ala Pro Lys Thr Ala Asp
210 215 220
Pro Gly Thr Met Lys Thr Thr Gly Lys Thr Gly Gly Gly Leu Ala Lys
225 230 235 240
Gly Thr Ile Arg Phe Lys Ser Glu Gly Gly Phe Ala Val Glu Asp Val
245 250 255
Gln Asp Gln Met Ile Gln Ala Glu Met Cys Gly Lys Leu Asn Glu Ile
260 265 270
Phe Asp Gln Tyr Leu Gly Val Gln Asp Asp Gln Leu Ala Met Arg Ile
275 280 285
Trp Glu Thr Ala Ser Asn Cys Glu Thr Leu Leu Gln Leu Ser Glu Ala
290 295 300
Ile Lys Glu Ser Glu Leu Ser Met Phe Asp Phe Pro Asp Gly Met Val
305 310 315 320
Phe Asp Met Trp Gly Ile Ile Gly Asp Leu Lys Arg Glu Gln Arg Glu
325 330 335
Lys Lys Pro Ser Pro Val Met Lys Asn Ala Ile Ser Arg Pro Ser Ala
340 345 350
Met Lys Leu Phe Glu
355
<210>31
<211>1002
<212>DNA
<213>人
<220>
<221>CDS
<222>(1)..(1002)
<400>31
atg ccg ctg gga ctg ggg cgg cgg aaa aag gcg ccc cct cta gtg gaa 48
Met Pro Leu Gly Leu Gly Arg Arg Lys Lys Ala Pro Pro Leu Val Glu
1 5 10 15
aat gag gag gct gag cca ggc cgt gga ggg ctg ggc gtg ggg gag cca 96
Asn Glu Glu Ala Glu Pro Gly Arg Gly Gly Leu Gly Val Gly Glu Pro
20 25 30
ggg cct ctg ggc gga ggt ggg tcg ggg ggc ccc caa atg ggc ttg ccc 144
Gly Pro Leu Gly Gly Gly Gly Ser Gly Gly Pro Gln Met Gly Leu Pro
35 40 45
ccc cct ccc cca gcc ctg cgg ccc cgc ctc gtg ttc cac acc cag ctg 192
Pro Pro Pro Pro Ala Leu Arg Pro Arg Leu Val Phe His Thr Gln Leu
50 55 60
gcc cat ggc agt ccc act ggc cgc atc gag ggc ttc acc aac gtc aag 240
Ala His Gly Ser Pro Thr Gly Arg Ile Glu Gly Phe Thr Asn Val Lys
65 70 75 80
gag ctg tat ggc aag atc gcc gag gcc ttc cgc ctg cca act gcc gag 288
Glu Leu Tyr Gly Lys Ile Ala Glu Ala Phe Arg Leu Pro Thr Ala Glu
85 90 95
gtg atg ttc tgc acc ctg aac acc cac aaa gtg gac atg gac aag ctc 336
Val Met Phe Cys Thr Leu Asn Thr His Lys Val Asp Met Asp Lys Leu
100 105 110
ctg ggg ggc cag atc ggg ctg gag gac ttc atc ttc gcc cac gtg aag 384
Leu Gly Gly Gln Ile Gly Leu Glu Asp Phe Ile Phe Ala His Val Lys
115 120 125
ggg cag cgc aag gag gtg gag gtg ttc aag tcg gag gat gca ctc ggg 432
Gly Gln Arg Lys Glu Val Glu Val Phe Lys Ser Glu Asp Ala Leu Gly
130 135 140
ctc acc atc acg gac aac ggg gct ggc tac gcc ttc atc aag cgc atc 480
Leu Thr Ile Thr Asp Asn Gly Ala Gly Tyr Ala Phe Ile Lys Arg Ile
145 150 155 160
aag gag ggc agc gtg atc gac cac atc cac ctc atc agc gtg ggc gac 528
Lys Glu Gly Ser Val Ile Asp His Ile His Leu Ile Ser Val Gly Asp
165 170 175
atg atc gag gcc att aac ggg cag agc ctg ctg ggc tgc cgg cac tac 576
Met Ile Glu Ala Ile Asn Gly Gln Ser Leu Leu Gly Cys Arg His Tyr
180 185 190
gag gtg gcc cgg ctg ctc aag gag ctg ccc cga ggc cgt acc ttc acg 624
Glu Val Ala Arg Leu Leu Lys Glu Leu Pro Arg Gly Arg Thr Phe Thr
195 200 205
ctg aag ctc acg gag cct cgc aag gcc ttc gac atg atc agc cag cgt 672
Leu Lys Leu Thr Glu Pro Arg Lys Ala Phe Asp Met Ile Ser Gln Arg
210 215 220
tca gcg ggt ggc cgc cct ggc tct ggc cca caa ctg ggc act ggc cga 720
Ser Ala Gly Gly Arg Pro Gly Ser Gly Pro Gln Leu Gly Thr Gly Arg
225 230 235 240
ggg acc ctg cgg ctc cga tcc cgg ggc ccc gcc acg gtg gag gat ctg 768
Gly Thr Leu Arg Leu Arg Ser Arg Gly Pro Ala Thr Val Glu Asp Leu
245 250 255
ccc tct gcc ttt gaa gag aag gcc att gag aag gtg gat gac ctg ctg 816
Pro Ser Ala Phe Glu Glu Lys Ala Ile Glu Lys Val Asp Asp Leu Leu
260 265 270
gag agt tac atg ggt atc agg gac acg gag ctg gcg gcc acc atg gtg 864
Glu Ser Tyr Met Gly Ile Arg Asp Thr Glu Leu Ala Ala Thr Met Val
275 280 285
gag ctg gga aag gac aaa agg aac ccg gat gag ctg gcc gag gcc ctg 912
Glu Leu Gly Lys Asp Lys Arg Asn Pro Asp Glu Leu Ala Glu Ala Leu
290 295 300
gac gaa cgg ctg ggt gac ttt gcc ttc cct gac gag ttc gtc ttt gac 960
Asp Glu Arg Leu Gly Asp Phe Ala Phe Pro Asp Glu Phe Val Phe Asp
305 310 315 320
gtc tgg ggc gcc att ggg gac gcc aag gtc ggc cgc tac tag 1002
Val Trp Gly Ala Ile Gly Asp Ala Lys Val Gly Arg Tyr
325 330
<210>32
<211>333
<212>PRT
<213>人
<400>32
Met Pro Leu Gly Leu Gly Arg Arg Lys Lys Ala Pro Pro Leu Val Glu
1 5 10 15
Asn Glu Glu Ala Glu Pro Gly Arg Gly Gly Leu Gly Val Gly Glu Pro
20 25 30
Gly Pro Leu Gly Gly Gly Gly Ser Gly Gly Pro Gln Met Gly Leu Pro
35 40 45
Pro Pro Pro Pro Ala Leu Arg Pro Arg Leu Val Phe His Thr Gln Leu
50 55 60
Ala His Gly Ser Pro Thr Gly Arg Ile Glu Gly Phe Thr Asn Val Lys
65 70 75 80
Glu Leu Tyr Gly Lys Ile Ala Glu Ala Phe Arg Leu Pro Thr Ala Glu
85 90 95
Val Met Phe Cys Thr Leu Asn Thr His Lys Val Asp Met Asp Lys Leu
100 105 110
Leu Gly Gly Gln Ile Gly Leu Glu Asp Phe Ile Phe Ala His Val Lys
115 120 125
Gly Gln Arg Lys Glu Val Glu Val Phe Lys Ser Glu Asp Ala Leu Gly
130 135 140
Leu Thr Ile Thr Asp Asn Gly Ala Gly Tyr Ala Phe Ile Lys Arg Ile
145 150 155 160
Lys Glu Gly Ser Val Ile Asp His Ile His Leu Ile Ser Val Gly Asp
165 170 175
Met Ile Glu Ala Ile Asn Gly Gln Ser Leu Leu Gly Cys Arg His Tyr
180 185 190
Glu Val Ala Arg Leu Leu Lys Glu Leu Pro Arg Gly Arg Thr Phe Thr
195 200 205
Leu Lys Leu Thr Glu Pro Arg Lys Ala Phe Asp Met Ile Ser Gln Arg
210 215 220
Ser Ala Gly Gly Arg Pro Gly Ser Gly Pro Gln Leu Gly Thr Gly Arg
225 230 235 240
Gly Thr Leu Arg Leu Arg Ser Arg Gly Pro Ala Thr Val Glu Asp Leu
245 250 255
Pro Ser Ala Phe Glu Glu Lys Ala Ile Glu Lys Val Asp Asp Leu Leu
260 265 270
Glu Ser Tyr Met Gly Ile Arg Asp Thr Glu Leu Ala Ala Thr Met Val
275 280 285
Glu Leu Gly Lys Asp Lys Arg Asn Pro Asp Glu Leu Ala Glu Ala Leu
290 295 300
Asp Glu Arg Leu Gly Asp Phe Ala Phe Pro Asp Glu Phe Val Phe Asp
305 310 315 320
Val Trp Gly Ala Ile Gly Asp Ala Lys Val Gly Arg Tyr
325 330
<210>33
<211>1293
<212>DNA
<213>线虫
<220>
<221>CDS
<222>(1)..(1293)
<400>33
atg gtc agc gtg gat cca ttg gca acg gag cgt tgg agg agc atc aga 48
Met Val Ser Val Asp Pro Leu Ala Thr Glu Arg Trp Arg Ser Ile Arg
1 5 10 15
aga tta aca gat cgc gac tct gca tat aaa gtt cca tgg ttt gtt ccc 96
Arg Leu Thr Asp Arg Asp Ser Ala Tyr Lys Val Pro Trp Phe Val Pro
20 25 30
gga ccg gaa aac ttt gaa gca ctg caa aac acg aag att ctt gtt att 144
Gly Pro Glu Asn Phe Glu Ala Leu Gln Asn Thr Lys Ile Leu Val Ile
35 40 45
ggt gct ggt gga ttg ggt tgt gag ttg tta aag aac ttg gct ttg agc 192
Gly Ala Gly Gly Leu Gly Cys Glu Leu Leu Lys Asn Leu Ala Leu Ser
50 55 60
gga ttc cga aca att gaa gtt atc gat atg gac aca att gat gta tca 240
Gly Phe Arg Thr Ile Glu Val Ile Asp Met Asp Thr Ile Asp Val Ser
65 70 75 80
aac cta aat cgt caa ttc tta ttt agg gaa tct gac gtt gga aaa tca 288
Asn Leu Asn Arg Gln Phe Leu Phe Arg Glu Ser Asp Val Gly Lys Ser
85 90 95
aaa gct gag gta gct gct gct ttc gtt caa caa aga gtt gtt gga tgt 336
Lys Ala Glu Val Ala Ala Ala Phe Val Gln Gln Arg Val Val Gly Cys
100 105 110
cag gtg act gcg cac aac tgt aga att gaa gac aag ggt caa gaa ttt 384
Gln Val Thr Ala His Asn Cys Arg Ile Glu Asp Lys Gly Gln Glu Phe
115 120 125
tat cga aaa ttc tct ata att atc tgt gga ctt gat tcg att cca gcc 432
Tyr Arg Lys Phe Ser Ile Ile Ile Cys Gly Leu Asp Ser Ile Pro Ala
130 135 140
aga aga tgg atc aac gga atg ctg tgt gat ttg gtt ttg gaa atg gcc 480
Arg Arg Trp Ile Asn Gly Met Leu Cys Asp Leu Val Leu Glu Met Ala
145 150 155 160
gac gga aaa cct gat gag aac aca att att cca atg att gac gga gga 528
Asp Gly Lys Pro Asp Glu Asn Thr Ile Ile Pro Met Ile Asp Gly Gly
165 170 175
act gaa gga ttt aaa gga aat gct cgt gtc ata tat ccg aaa ttc aca 576
Thr Glu Gly Phe Lys Gly Asn Ala Arg Val Ile Tyr Pro Lys Phe Thr
180 185 190
gcc tgt att gat tgt act ctt gat ctt tat cca cct caa gtc aat ttt 624
Ala Cys Ile Asp Cys Thr Leu Asp Leu Tyr Pro Pro Gln Val Asn Phe
195 200 205
cca ttg tgc aca att gct cac act cct cga ctt cca gaa cat tgt att 672
Pro Leu Cys Thr Ile Ala His Thr Pro Arg Leu Pro Glu His Cys Ile
210 215 220
gaa tac att aaa gta gtt gtt tgg cca gag gaa aaa cca ttt gaa ggt 720
Glu Tyr Ile Lys Val Val Val Trp Pro Glu Glu Lys Pro Phe Glu Gly
225 230 235 240
gtt tct ctt gac gct gac gat ccg atc cac gtt gaa tgg gtt ctc gaa 768
Val Ser Leu Asp Ala Asp Asp Pro Ile His Val Glu Trp Val Leu Glu
245 250 255
aga gca agt ctt cgt gca gaa aaa tac aat att cga ggt gtg gat cgt 816
Arg Ala Ser Leu Arg Ala Glu Lys Tyr Asn Ile Arg Gly Val Asp Arg
260 265 270
cgt ttg aca tct gga gtt cta aaa aga att att ccg gct gtt gca tca 864
Arg Leu Thr Ser Gly Val Leu Lys Arg Ile Ile Pro Ala Val Ala Ser
275 280 285
aca aat gca gtt atc gct gca tca tgt gcc cta gaa gct ctg aaa ttg 912
Thr Asn Ala Val Ile Ala Ala Ser Cys Ala Leu Glu Ala Leu Lys Leu
290 295 300
gcc aca aac att gcc aaa cca atc gat aat tat ctt aat ttc act caa 960
Ala Thr Asn Ile Ala Lys Pro Ile Asp Asn Tyr Leu Asn Phe Thr Gln
305 310 315 320
att cac gga gca tat acc agt gtt gtt tca atg atg aaa gat gac aat 1008
Ile His Gly Ala Tyr Thr Ser Val Val Ser Met Met Lys Asp Asp Asn
325 330 335
tgt ctc act tgt agt ggt ggg cgt ctt cca ttc gaa gtt tca cca tct 1056
Cys Leu Thr Cys Ser Gly Gly Arg Leu Pro Phe Glu Val Ser Pro Ser
340 345 350
tca act ctt gaa tcg ctt atc atc aga ctc tcg gag cgt ttc cat ctc 1104
Ser Thr Leu Glu Ser Leu Ile Ile Arg Leu Ser Glu Arg Phe His Leu
355 360 365
aaa cat ccg aca cta gcg acc tca act cga aaa ctt tac tgt att agc 1152
Lys His Pro Thr Leu Ala Thr Ser Thr Arg Lys Leu Tyr Cys Ile Ser
370 375 380
agt ttc atg cca caa ttt gaa caa gaa agc aaa gaa aat ctg cat act 1200
Ser Phe Met Pro Gln Phe Glu Gln Glu Ser Lys Glu Asn Leu His Thr
385 390 395 400
tcg atg aaa gat ctt gtt agc gat ggc gaa gaa ata ctg gta tcc gac 1248
Ser Met Lys Asp Leu Val Ser Asp Gly Glu Glu Ile Leu Val Ser Asp
405 410 415
gaa gca ttg tct cgt gca ctt aca cta cga att cag ctc atc taa 1293
Glu Ala Leu Ser Arg Ala Leu Thr Leu Arg Ile Gln Leu Ile
420 425 430
<210>34
<211>430
<212>PRT
<213>线虫
<400>34
Met Val Ser Val Asp Pro Leu Ala Thr Glu Arg Trp Arg Ser Ile Arg
1 5 10 15
Arg Leu Thr Asp Arg Asp Ser Ala Tyr Lys Val Pro Trp Phe Val Pro
20 25 30
Gly Pro Glu Asn Phe Glu Ala Leu Gln Asn Thr Lys Ile Leu Val Ile
35 40 45
Gly Ala Gly Gly Leu Gly Cys Glu Leu Leu Lys Asn Leu Ala Leu Ser
50 55 60
Gly Phe Arg Thr Ile Glu Val Ile Asp Met Asp Thr Ile Asp Val Ser
65 70 75 80
Asn Leu Asn Arg Gln Phe Leu Phe Arg Glu Ser Asp Val Gly Lys Ser
85 90 95
Lys Ala Glu Val Ala Ala Ala Phe Val Gln Gln Arg Val Val Gly Cys
100 105 110
Gln Val Thr Ala His Asn Cys Arg Ile Glu Asp Lys Gly Gln Glu Phe
115 120 125
Tyr Arg Lys Phe Ser Ile Ile Ile Cys Gly Leu Asp Ser Ile Pro Ala
130 135 140
Arg Arg Trp Ile Asn Gly Met Leu Cys Asp Leu Val Leu Glu Met Ala
145 150 155 160
Asp Gly Lys Pro Asp Glu Asn Thr Ile Ile Pro Met Ile Asp Gly Gly
165 170 175
Thr Glu Gly Phe Lys Gly Asn Ala Arg Val Ile Tyr Pro Lys Phe Thr
180 185 190
Ala Cys Ile Asp Cys Thr Leu Asp Leu Tyr Pro Pro Gln Val Asn Phe
195 200 205
Pro Leu Cys Thr Ile Ala His Thr Pro Arg Leu Pro Glu His Cys Ile
210 215 220
Glu Tyr Ile Lys Val Val Val Trp Pro Glu Glu Lys Pro Phe Glu Gly
225 230 235 240
Val Ser Leu Asp Ala Asp Asp Pro Ile His Val Glu Trp Val Leu Glu
245 250 255
Arg Ala Ser Leu Arg Ala Glu Lys Tyr Asn Ile Arg Gly Val Asp Arg
260 265 270
Arg Leu Thr Ser Gly Val Leu Lys Arg Ile Ile Pro Ala Val Ala Ser
275 280 285
Thr Asn Ala Val Ile Ala Ala Ser Cys Ala Leu Glu Ala Leu Lys Leu
290 295 300
Ala Thr Asn Ile Ala Lys Pro Ile Asp Asn Tyr Leu Asn Phe Thr Gln
305 310 315 320
Ile His Gly Ala Tyr Thr Ser Val Val Ser Met Met Lys Asp Asp Asn
325 330 335
Cys Leu Thr Cys Ser Gly Gly Arg Leu Pro Phe Glu Val Ser Pro Ser
340 345 350
Ser Thr Leu Glu Ser Leu Ile Ile Arg Leu Ser Glu Arg Phe His Leu
355 360 365
Lys His Pro Thr Leu Ala Thr Ser Thr Arg Lys Leu Tyr Cys Ile Ser
370 375 380
Ser Phe Met Pro Gln Phe Glu Gln Glu Ser Lys Glu Asn Leu His Thr
385 390 395 400
Ser Met Lys Asp Leu Val Ser Asp Gly Glu Glu Ile Leu Val Ser Asp
405 410 415
Glu Ala Leu Ser Arg Ala Leu Thr Leu Arg Ile Gln Leu Ile
420 425 430
<210>35
<211>1392
<212>DNA
<213>人
<220>
<221>CDS
<222>(1)..(1392)
<400>35
atg gcg gat ggc gag gag ccg gag aag aaa aga agg aga ata gag gag 48
Met Ala Asp Gly Glu Glu Pro Glu Lys Lys Arg Arg Arg Ile Glu Glu
1 5 10 15
ctg ctg gct gag aaa atg gct gtt gat ggt ggg tgt ggg gac act gga 96
Leu Leu Ala Glu Lys Met Ala Val Asp Gly Gly Cys Gly Asp Thr Gly
20 25 30
gac tgg gaa ggt cgc tgg aac cat gta aag aag ttc ctc gag cga tct 144
Asp Trp Glu Gly Arg Trp Asn His Val Lys Lys Phe Leu Glu Arg Ser
35 40 45
gga ccc ttc aca cac cct gat ttc gaa ccg agc act gaa tct ctc cag 192
Gly Pro Phe Thr His Pro Asp Phe Glu Pro Ser Thr Glu Ser Leu Gln
50 55 60
ttc ttg tta gat aca tgt aaa gtt cta gtc att gga gct ggc ggc tta 240
Phe Leu Leu Asp Thr Cys Lys Val Leu Val Ile Gly Ala Gly Gly Leu
65 70 75 80
gga tgt gag ctc ctg aaa aat ctg gcc ttg tct ggt ttt aga cag att 288
Gly Cys Glu Leu Leu Lys Asn Leu Ala Leu Ser Gly Phe Arg Gln Ile
85 90 95
cat gtt ata gat atg gac act ata gat gtt tcc aat cta aat agg cag 336
His Val Ile Asp Met Asp Thr Ile Asp Val Ser Asn Leu Asn Arg Gln
100 105 110
ttt tta ttt agg cct aaa gat att gga aga cct aag gct gaa gtt gct 384
Phe Leu Phe Arg Pro Lys Asp Ile Gly Arg Pro Lys Ala Glu Val Ala
115 120 125
gca gaa ttt cta aat gac aga gtt cct aat tgc aat gta gtt cca cat 432
Ala Glu Phe Leu Asn Asp Arg Val Pro Asn Cys Asn Val Val Pro His
130 135 140
ttc aac aag att caa gat ttt aac gac act ttc tat cga caa ttt cat 480
Phe Asn Lys Ile Gln Asp Phe Asn Asp Thr Phe Tyr Arg Gln Phe His
145 150 155 160
att att gta tgt gga ctg gac tct atc atc gcc aga aga tgg ata aat 528
Ile Ile Val Cys Gly Leu Asp Ser Ile Ile Ala Arg Arg Trp Ile Asn
165 170 175
ggc atg ctg ata tct ctt cta aat tat gaa gat ggt gtc tta gat cca 576
Gly Met Leu Ile Ser Leu Leu Asn Tyr Glu Asp Gly Val Leu Asp Pro
180 185 190
agc tcc att gtc cct ttg ata gat ggg ggg aca gaa ggt ttt aaa gga 624
Ser Ser Ile Val Pro Leu Ile Asp Gly Gly Thr Glu Gly Phe Lys Gly
195 200 205
aat gcc cgg gtg att ctg cct gga atg act gct tgt atc gaa tgc acg 672
Asn Ala Arg Val Ile Leu Pro Gly Met Thr Ala Cys Ile Glu Cys Thr
210 215 220
ctg gaa ctt tat cca cca cag gtt aat ttt ccc atg tgc acc att gca 720
Leu Glu Leu Tyr Pro Pro Gln Val Asn Phe Pro Met Cys Thr Ile Ala
225 230 235 240
tct atg ccc agg cta cca gaa cac tgt att gag tat gta agg atg ttg 768
Ser Met Pro Arg Leu Pro Glu His Cys Ile Glu Tyr Val Arg Met Leu
245 250 255
cag tgg cct aag gag cag cct ttt gga gaa ggg gtt cca tta gat gga 816
Gln Trp Pro Lys Glu Gln Pro Phe Gly Glu Gly Val Pro Leu Asp Gly
260 265 270
gat gat cct gaa cat ata caa tgg att ttc caa aaa tcc cta gag aga 864
Asp Asp Pro Glu His Ile Gln Trp Ile Phe Gln Lys Ser Leu Glu Arg
275 280 285
gca tca caa tat aat att agg ggt gtt acg tat agg ctc act caa ggg 912
Ala Ser Gln Tyr Asn Ile Arg Gly Val Thr Tyr Arg Leu Thr Gln Gly
290 295 300
gta gta aaa aga atc att cct gca gta gct tcc aca aat gca gtc att 960
Val Val Lys Arg Ile Ile Pro Ala Val Ala Ser Thr Asn Ala Val Ile
305 310 315 320
gca gct gtg tgt gcc act gag gtt ttt aaa ata gcc aca agt gca tac 1008
Ala Ala Val Cys Ala Thr Glu Val Phe Lys Ile Ala Thr Ser Ala Tyr
325 330 335
att ccc ttg aat aat tac ttg gtg ttt aat gat gta gat ggg ctg tat 1056
Ile Pro Leu Asn Asn Tyr Leu Val Phe Asn Asp Val Asp Gly Leu Tyr
340 345 350
aca tac aca ttt gaa gca gaa aga aag gaa aac tgc cca gct tgt agc 1104
Thr Tyr Thr Phe Glu Ala Glu Arg Lys Glu Asn Cys Pro Ala Cys Ser
355 360 365
cag ctt cct caa aat att cag ttt tct cca tca gct aaa cta cag gag 1152
Gln Leu Pro Gln Asn Ile Gln Phe Ser Pro Ser Ala Lys Leu Gln Glu
370 375 380
gtt ttg gat tat cta acc aat agt gct tct ctg caa atg aaa tct cca 1200
Val Leu Asp Tyr Leu Thr Asn Ser Ala Ser Leu Gln Met Lys Ser Pro
385 390 395 400
gcc atc aca gcc acc cta gag gga aaa aat aga aca ctt tac tta cag 1248
Ala Ile Thr Ala Thr Leu Glu Gly Lys Asn Arg Thr Leu Tyr Leu Gln
405 410 415
tcg gta acc tct att gaa gaa cga aca agg cca aat ctc tcc aaa aca 1296
Ser Val Thr Ser Ile Glu Glu Arg Thr Arg Pro Asn Leu Ser Lys Thr
420 425 430
ttg aaa gaa ttg ggg ctt gtt gat gga caa gaa ctg gcg gtt gct gat 1344
Leu Lys Glu Leu Gly Leu Val Asp Gly Gln Glu Leu Ala Val Ala Asp
435 440 445
gtc acc acc cca cag act gta cta ttc aaa ctt cat ttt act tct taa 1392
Val Thr Thr Pro Gln Thr Val Leu Phe Lys Leu His Phe Thr Ser
450 455 460
<210>36
<211>463
<212>PRT
<213>人
<400>36
Met Ala Asp Gly Glu Glu Pro Glu Lys Lys Arg Arg Arg Ile Glu Glu
1 5 10 15
Leu Leu Ala Glu Lys Met Ala Val Asp Gly Gly Cys Gly Asp Thr Gly
20 25 30
Asp Trp Glu Gly Arg Trp Asn His Val Lys Lys Phe Leu Glu Arg Ser
35 40 45
Gly Pro Phe Thr His Pro Asp Phe Glu Pro Ser Thr Glu Ser Leu Gln
50 55 60
Phe Leu Leu Asp Thr Cys Lys Val Leu Val Ile Gly Ala Gly Gly Leu
65 70 75 80
Gly Cys Glu Leu Leu Lys Asn Leu Ala Leu Ser Gly Phe Arg Gln Ile
85 90 95
His Val Ile Asp Met Asp Thr Ile Asp Val Ser Asn Leu Asn Arg Gln
100 105 110
Phe Leu Phe Arg Pro Lys Asp Ile Gly Arg Pro Lys Ala Glu Val Ala
115 120 125
Ala Glu Phe Leu Asn Asp Arg Val Pro Asn Cys Asn Val Val Pro His
130 135 140
Phe Asn Lys Ile Gln Asp Phe Asn Asp Thr Phe Tyr Arg Gln Phe His
145 150 155 160
Ile Ile Val Cys Gly Leu Asp Ser Ile Ile Ala Arg Arg Trp Ile Asn
165 170 175
Gly Met Leu Ile Ser Leu Leu Asn Tyr Glu Asp Gly Val Leu Asp Pro
180 185 190
Ser Ser Ile Val Pro Leu Ile Asp Gly Gly Thr Glu Gly Phe Lys Gly
195 200 205
Asn Ala Arg Val Ile Leu Pro Gly Met Thr Ala Cys Ile Glu Cys Thr
210 215 220
Leu Glu Leu Tyr Pro Pro Gln Val Asn Phe Pro Met Cys Thr Ile Ala
225 230 235 240
Ser Met Pro Arg Leu Pro Glu His Cys Ile Glu Tyr Val Arg Met Leu
245 250 255
Gln Trp Pro Lys Glu Gln Pro Phe Gly Glu Gly Val Pro Leu Asp Gly
260 265 270
Asp Asp Pro Glu His Ile Gln Trp Ile Phe Gln Lys Ser Leu Glu Arg
275 280 285
Ala Ser Gln Tyr Asn Ile Arg Gly Val Thr Tyr Arg Leu Thr Gln Gly
290 295 300
Val Val Lys Arg Ile Ile Pro Ala Val Ala Ser Thr Asn Ala Val Ile
305 310 315 320
Ala Ala Val Cys Ala Thr Glu Val Phe Lys Ile Ala Thr Ser Ala Tyr
325 330 335
Ile Pro Leu Asn Asn Tyr Leu Val Phe Asn Asp Val Asp Gly Leu Tyr
340 345 350
Thr Tyr Thr Phe Glu Ala Glu Arg Lys Glu Asn Cys Pro Ala Cys Ser
355 360 365
Gln Leu Pro Gln Asn Ile Gln Phe Ser Pro Ser Ala Lys Leu Gln Glu
370 375 380
Val Leu Asp Tyr Leu Thr Asn Ser Ala Ser Leu Gln Met Lys Ser Pro
385 390 395 400
Ala Ile Thr Ala Thr Leu Glu Gly Lys Asn Arg Thr Leu Tyr Leu Gln
405 410 415
Ser Val Thr Ser Ile Glu Glu Arg Thr Arg Pro Asn Leu Ser Lys Thr
420 425 430
Leu Lys Glu Leu Gly Leu Val Asp Gly Gln Glu Leu Ala Val Ala Asp
435 440 445
Val Thr Thr Pro Gln Thr Val Leu Phe Lys Leu His Phe Thr Ser
450 455 460
<210>37
<211>486
<212>DNA
<213>线虫
<220>
<221>CDS
<222>(1)..(486)
<400>37
atg ggt gat gac gac cgt tgc aag acg gga att ctt atc cgg tgt ctt 48
Met Gly Asp Asp Asp Arg Cys Lys Thr Gly Ile Leu Ile Arg Cys Leu
1 5 10 15
ggc gat ctt caa gaa atg gag gac ggc tac ctt cgc aaa atg gaa gtc 96
Gly Asp Leu Gln Glu Met Glu Asp Gly Tyr Leu Arg Lys Met Glu Val
20 25 30
atg gag aaa gaa cag gtg gct gcc gaa aaa cga ctt gtt gaa tgc agg 144
Met Glu Lys Glu Gln Val Ala Ala Glu Lys Arg Leu Val Glu Cys Arg
35 40 45
gaa gac gtt gca aag tta cgg gca gaa aac gca cag ttg gcg acc gat 192
Glu Asp Val Ala Lys Leu Arg Ala Glu Asn Ala Gln Leu Ala Thr Asp
50 55 60
atc gac aat ctc aag act gca acc gaa aac acc gga cgc ctc aat gca 240
Ile Asp Asn Leu Lys Thr Ala Thr Glu Asn Thr Gly Arg Leu Asn Ala
65 70 75 80
gaa att gcc cag tta cga acg gaa ctg tcc gcc gtg ccc cgc cct tgt 288
Glu Ile Ala Gln Leu Arg Thr Glu Leu Ser Ala Val Pro Arg Pro Cys
85 90 95
tgc gcg gtt tgt cac gat tca tac gcc tcc cgc ggt cca aaa aaa ccc 336
Cys Ala Val Cys His Asp Ser Tyr Ala Ser Arg Gly Pro Lys Lys Pro
100 105 110
aag gtt tgt tcc tgt ctg cac act tat tgt ggc gcg tgc att agg gaa 384
Lys Val Cys Ser Cys Leu His Thr Tyr Cys Gly Ala Cys Ile Arg Glu
115 120 125
att tcg agc cgc cac aat ggt gaa atg aaa tgc ccc gaa tgc gtt gcg 432
Ile Ser Ser Arg His Asn Gly Glu Met Lys Cys Pro Glu Cys Val Ala
130 135 140
gac gtc cgc ata ctg gga aca aac ttt ggg ata aca aat gcg ttt cgg 480
Asp Val Arg Ile Leu Gly Thr Asn Phe Gly Ile Thr Asn Ala Phe Arg
145 150 155 160
tca tga 486
Ser
<210>38
<211>161
<212>PRT
<213>线虫
<400>38
Met Gly Asp Asp Asp Arg Cys Lys Thr Gly Ile Leu Ile Arg Cys Leu
1 5 10 15
Gly Asp Leu Gln Glu Met Glu Asp Gly Tyr Leu Arg Lys Met Glu Val
20 25 30
Met Glu Lys Glu Gln Val Ala Ala Glu Lys Arg Leu Val Glu Cys Arg
35 40 45
Glu Asp Val Ala Lys Leu Arg Ala Glu Asn Ala Gln Leu Ala Thr Asp
50 55 60
Ile Asp Asn Leu Lys Thr Ala Thr Glu Asn Thr Gly Arg Leu Asn Ala
65 70 75 80
Glu Ile Ala Gln Leu Arg Thr Glu Leu Ser Ala Val Pro Arg Pro Cys
85 90 95
Cys Ala Val Cys His Asp Ser Tyr Ala Ser Arg Gly Pro Lys Lys Pro
100 105 110
Lys Val Cys Ser Cys Leu His Thr Tyr Cys Gly Ala Cys Ile Arg Glu
115 120 125
Ile Ser Ser Arg His Asn Gly Glu Met Lys Cys Pro Glu Cys Val Ala
130 135 140
Asp Val Arg Ile Leu Gly Thr Asn Phe Gly Ile Thr Asn Ala Phe Arg
145 150 155 160
Ser
<210>39
<211>2235
<212>DNA
<213>人
<220>
<221>CDS
<222>(1)..(2235)
<400>39
atg gcc agt gaa ggc acc aac atc cca agt cct gtg gtg cgc cag att 48
Met Ala Ser Glu Gly Thr Asn Ile Pro Ser Pro Val Val Arg Gln Ile
1 5 10 15
gac aag cag ttt ctg att tgc agt ata tgc ctg gaa cgg tac aag aat 96
Asp Lys Gln Phe Leu Ile Cys Ser Ile Cys Leu Glu Arg Tyr Lys Asn
20 25 30
ccc aag gtt ctc ccc tgt ctg cac act ttc tgc gag agg tgc ctg cag 144
Pro Lys Val Leu Pro Cys Leu His Thr Phe Cys Glu Arg Cys Leu Gln
35 40 45
aac tac att cct gcc cac agt tta acc ctc tcc tgc cca gtg tgc cgc 192
Asn Tyr Ile Pro Ala His Ser Leu Thr Leu Ser Cys Pro Val Cys Arg
50 55 60
cag acc tcc atc ctg ccc gag aaa ggg gtg gcc gcg ctc cag aac aat 240
Gln Thr Ser Ile Leu Pro Glu Lys Gly Val Ala Ala Leu Gln Asn Asn
65 70 75 80
ttc ttc atc aca aac ctg atg gac gtg ctg cag cga act cca ggc agc 288
Phe Phe Ile Thr Asn Leu Met Asp Val Leu Gln Arg Thr Pro Gly Ser
85 90 95
aac gct gag gag tct tcc atc ctg gag aca gtc act gct gtg gct gcg 336
Asn Ala Glu Glu Ser Ser Ile Leu Glu Thr Val Thr Ala Val Ala Ala
100 105 110
gga aag cct ctc tct tgc cca aac cac gat ggg aat gtg atg gaa ttt 384
Gly Lys Pro Leu Ser Cys Pro Asn His Asp Gly Asn Val Met Glu Phe
115 120 125
tac tgc cag tcc tgt gag act gcc atg tgt cgg gag tgc acg gag ggg 432
Tyr Cys Gln Ser Cys Glu Thr Ala Met Cys Arg Glu Cys Thr Glu Gly
130 135 140
gag cac gca gag cac ccc aca gtt cca ctc aag gat gtg gtg gaa cag 480
Glu His Ala Glu His Pro Thr Val Pro Leu Lys Asp Val Val Glu Gln
145 150 155 160
cac aag gcc tcg ctc cag gtc cag ctg gat gct gtc aac aaa agg ctc 528
His Lys Ala Ser Leu Gln Val Gln Leu Asp Ala Val Asn Lys Arg Leu
165 170 175
cca gaa ata gat tct gct ctt cag ttc atc tct gaa atc att cat cag 576
Pro Glu Ile Asp Ser Ala Leu Gln Phe Ile Ser Glu Ile Ile His Gln
180 185 190
tta acc aac caa aag gcc agc atc gtg gat gac att cat tcc acc ttt 624
Leu Thr Asn Gln Lys Ala Ser Ile Val Asp Asp Ile His Ser Thr Phe
195 200 205
gat gag ctc cag aag act tta aat gtg cgc aag agt gtg ctg ctt atg 672
Asp Glu Leu Gln Lys Thr Leu Asn Val Arg Lys Ser Val Leu Leu Met
210 215 220
gaa ttg gag gtc aac tat ggc ctc aaa cac aaa gtc ctc cag tcg cag 720
Glu Leu Glu Val Asn Tyr Gly Leu Lys His Lys Val Leu Gln Ser Gln
225 230 235 240
ctg gat act ctg ctc cag ggg cag gag agc att aag agc tgc agc aac 768
Leu Asp Thr Leu Leu Gln Gly Gln Glu Ser Ile Lys Ser Cys Ser Asn
245 250 255
ttc aca gcg cag gcc ctc aac cat ggc acg gag acc gag gtc cta ctg 816
Phe Thr Ala Gln Ala Leu Asn His Gly Thr Glu Thr Glu Val Leu Leu
260 265 270
gtg aag aag cag atg agc gag aag ctg aac gag ctg gcc gac cag gac 864
Val Lys Lys Gln Met Ser Glu Lys Leu Asn Glu Leu Ala Asp Gln Asp
275 280 285
ttc ccc ttg cac ccg cgg gag aac gac cag ctg gat ttc atc gtg gaa 912
Phe Pro Leu His Pro Arg Glu Asn Asp Gln Leu Asp Phe Ile Val Glu
290 295 300
acc gag ggg ctg aag aag tcc atc cac aac ctc ggg acg atc tta acc 960
Thr Glu Gly Leu Lys Lys Ser Ile His Asn Leu Gly Thr Ile Leu Thr
305 310 315 320
acc aac gcc gtt gcc tca gag aca gtg gcc acg ggc gag ggg ctg cgg 1008
Thr Asn Ala Val Ala Ser Glu Thr Val Ala Thr Gly Glu Gly Leu Arg
325 330 335
cag acc atc atc ggg cag ccc atg tcc gtc acc atc acc acc aag gac 1056
Gln Thr Ile Ile Gly Gln Pro Met Ser Val Thr Ile Thr Thr Lys Asp
340 345 350
aaa gac ggt gag ctg tgc aaa acc ggc aac gcc tac ctc acc gcc gaa 1104
Lys Asp Gly Glu Leu Cys Lys Thr Gly Asn Ala Tyr Leu Thr Ala Glu
355 360 365
ctg agc acc ccc gac ggg agc gtg gca gac ggg gag atc ctg gac aac 1152
Leu Ser Thr Pro Asp Gly Ser Val Ala Asp Gly Glu Ile Leu Asp Asn
370 375 380
aag aac ggc acc tat gag ttt ttg tac act gtc cag aag gaa ggg gac 1200
Lys Asn Gly Thr Tyr Glu Phe Leu Tyr Thr Val Gln Lys Glu Gly Asp
385 390 395 400
ttt acc ctg tct ctg aga ctc tat gac cag cac atc cga ggc agc ccg 1248
Phe Thr Leu Ser Leu Arg Leu Tyr Asp Gln His Ile Arg Gly Ser Pro
405 410 415
ttt aag ctg aaa gtg atc cga tcc gct gat gtg tct ccc acc aca gaa 1296
Phe Lys Leu Lys Val Ile Arg Ser Ala Asp Val Ser Pro Thr Thr Glu
420 425 430
ggc gtg aag agg cgc gtt aag tcc ccg ggg agc ggc cac gtc aag cag 1344
Gly Val Lys Arg Arg Val Lys Ser Pro Gly Ser Gly His Val Lys Gln
435 440 445
aaa gct gtg aaa aga ccc gca agc atg tac agc act gga aaa cga aaa 1392
Lys Ala Val Lys Arg Pro Ala Ser Met Tyr Ser Thr Gly Lys Arg Lys
450 455 460
gag aat ccc atc gaa gac gat ttg atc ttt cga gtg ggt acc aaa gga 1440
Glu Asn Pro Ile Glu Asp Asp Leu Ile Phe Arg Val Gly Thr Lys Gly
465 470 475 480
aga aat aaa gga gag ttt aca aat ctt cag ggg gta gct gca tct aca 1488
Arg Asn Lys Gly Glu Phe Thr Asn Leu Gln Gly Val Ala Ala Ser Thr
485 490 495
aat gga aag ata tta att gca gac agt aac aac caa tgt gtg cag ata 1536
Asn Gly Lys Ile Leu Ile Ala Asp Ser Asn Asn Gln Cys Val Gln Ile
500 505 510
ttt tcc aat gat ggc cag ttc aaa agt cgt ttt ggc ata cgg gga cgc 1584
Phe Ser Asn Asp Gly Gln Phe Lys Ser Arg Phe Gly Ile Arg Gly Arg
515 520 525
tct ccg ggg cag ctg cag cgg ccc aca gga gtg gct gta cat ccc agt 1632
Ser Pro Gly Gln Leu Gln Arg Pro Thr Gly Val Ala Val His Pro Ser
530 535 540
ggg gac ata atc att gcc gat tat gat aat aaa tgg gtc agc att ttc 1680
Gly Asp Ile Ile Ile Ala Asp Tyr Asp Asn Lys Trp Val Ser Ile Phe
545 550 555 560
tcc tcc gat ggg aaa ttt aag aca aaa att gga tca gga aag ctg atg 1728
Ser Ser Asp Gly Lys Phe Lys Thr Lys Ile Gly Ser Gly Lys Leu Met
565 570 575
gga ccc aaa gga gtt tct gtg gac cgc aat ggg cac att att gtt gtg 1776
Gly Pro Lys Gly Val Ser Val Asp Arg Asn Gly His Ile Ile Val Val
580 585 590
gac aac aag gcg tgc tgc gtg ttt atc ttc cag cca aac ggg aaa ata 1824
Asp Asn Lys Ala Cys Cys Val Phe Ile Phe Gln Pro Asn Gly Lys Ile
595 600 605
gtc acc agg ttt ggt agc cga gga aat ggg gac agg cag ttt gca ggt 1872
Val Thr Arg Phe Gly Ser Arg Gly Asn Gly Asp Arg Gln Phe Ala Gly
610 615 620
ccc cat ttt gca gct gta aat agc aat aat gag att att att aca gat 1920
Pro His Phe Ala Ala Val Asn Ser Asn Asn Glu Ile Ile Ile Thr Asp
625 630 635 640
ttc cat aat cat tct gtc aag gtg ttt aat cag gaa gga gaa ttc atg 1968
Phe His Asn His Ser Val Lys Val Phe Asn Gln Glu Gly Glu Phe Met
645 650 655
ttg aag ttt ggc tca aat gga gaa gga aat ggg cag ttt aat gct cca 2016
Leu Lys Phe Gly Ser Asn Gly Glu Gly Asn Gly Gln Phe Asn Ala Pro
660 665 670
aca ggt gta gca gtg gat tca aat gga aac atc att gtg gcc gac tgg 2064
Thr Gly Val Ala Val Asp Ser Asn Gly Asn Ile Ile Val Ala Asp Trp
675 680 685
gga aac agc agg atc cag gtt ttt gat ggg agt gga tca ttt ttg tcc 2112
Gly Asn Ser Arg Ile Gln Val Phe Asp Gly Ser Gly Ser Phe Leu Ser
690 695 700
tac att aac aca tct gct gac cca ctc tat ggc ccc caa ggc ctg gcc 2160
Tyr Ile Asn Thr Ser Ala Asp Pro Leu Tyr Gly Pro Gln Gly Leu Ala
705 710 715 720
cta act tca gat ggt cat gtt gtg gtt gca gac tct gga aat cac tgt 2208
Leu Thr Ser Asp Gly His Val Val Val Ala Asp Ser Gly Asn His Cys
725 730 735
ttc aaa gtc tat cga tac tta cag taa 2235
Phe Lys Val Tyr Arg Tyr Leu Gln
740
<210>40
<211>744
<212>PRT
<213>人
<400>40
Met Ala Ser Glu Gly Thr Asn Ile Pro Ser Pro Val Val Arg Gln Ile
1 5 10 15
Asp Lys Gln Phe Leu Ile Cys Ser Ile Cys Leu Glu Arg Tyr Lys Asn
20 25 30
Pro Lys Val Leu Pro Cys Leu His Thr Phe Cys Glu Arg Cys Leu Gln
35 40 45
Asn Tyr Ile Pro Ala His Ser Leu Thr Leu Ser Cys Pro Val Cys Arg
50 55 60
Gln Thr Ser Ile Leu Pro Glu Lys Gly Val Ala Ala Leu Gln Asn Asn
65 70 75 80
Phe Phe Ile Thr Asn Leu Met Asp Val Leu Gln Arg Thr Pro Gly Ser
85 90 95
Asn Ala Glu Glu Ser Ser Ile Leu Glu Thr Val Thr Ala Val Ala Ala
100 105 110
Gly Lys Pro Leu Ser Cys Pro Asn His Asp Gly Asn Val Met Glu Phe
115 120 125
Tyr Cys Gln Ser Cys Glu Thr Ala Met Cys Arg Glu Cys Thr Glu Gly
130 135 140
Glu His Ala Glu His Pro Thr Val Pro Leu Lys Asp Val Val Glu Gln
145 150 155 160
His Lys Ala Ser Leu Gln Val Gln Leu Asp Ala Val Asn Lys Arg Leu
165 170 175
Pro Glu Ile Asp Ser Ala Leu Gln Phe Ile Ser Glu Ile Ile His Gln
180 185 190
Leu Thr Asn Gln Lys Ala Ser Ile Val Asp Asp Ile His Ser Thr Phe
195 200 205
Asp Glu Leu Gln Lys Thr Leu Asn Val Arg Lys Ser Val Leu Leu Met
210 215 220
Glu Leu Glu Val Asn Tyr Gly Leu Lys His Lys Val Leu Gln Ser Gln
225 230 235 240
Leu Asp Thr Leu Leu Gln Gly Gln Glu Ser Ile Lys Ser Cys Ser Asn
245 250 255
Phe Thr Ala Gln Ala Leu Asn His Gly Thr Glu Thr Glu Val Leu Leu
260 265 270
Val Lys Lys Gln Met Ser Glu Lys Leu Asn Glu Leu Ala Asp Gln Asp
275 280 285
Phe Pro Leu His Pro Arg Glu Asn Asp Gln Leu Asp Phe Ile Val Glu
290 295 300
Thr Glu Gly Leu Lys Lys Ser Ile His Asn Leu Gly Thr Ile Leu Thr
305 310 315 320
Thr Asn Ala Val Ala Ser Glu Thr Val Ala Thr Gly Glu Gly Leu Arg
325 330 335
Gln Thr Ile Ile Gly Gln Pro Met Ser Val Thr Ile Thr Thr Lys Asp
340 345 350
Lys Asp Gly Glu Leu Cys Lys Thr Gly Asn Ala Tyr Leu Thr Ala Glu
355 360 365
Leu Ser Thr Pro Asp Gly Ser Val Ala Asp Gly Glu Ile Leu Asp Asn
370 375 380
Lys Asn Gly Thr Tyr Glu Phe Leu Tyr Thr Val Gln Lys Glu Gly Asp
385 390 395 400
Phe Thr Leu Ser Leu Arg Leu Tyr Asp Gln His Ile Arg Gly Ser Pro
405 410 415
Phe Lys Leu Lys Val Ile Arg Ser Ala Asp Val Ser Pro Thr Thr Glu
420 425 430
Gly Val Lys Arg Arg Val Lys Ser Pro Gly Ser Gly His Val Lys Gln
435 440 445
Lys Ala Val Lys Arg Pro Ala Ser Met Tyr Ser Thr Gly Lys Arg Lys
450 455 460
Glu Asn Pro Ile Glu Asp Asp Leu Ile Phe Arg Val Gly Thr Lys Gly
465 470 475 480
Arg Asn Lys Gly Glu Phe Thr Asn Leu Gln Gly Val Ala Ala Ser Thr
485 490 495
Asn Gly Lys Ile Leu Ile Ala Asp Ser Asn Asn Gln Cys Val Gln Ile
500 505 510
Phe Ser Asn Asp Gly Gln Phe Lys Ser Arg Phe Gly Ile Arg Gly Arg
515 520 525
Ser Pro Gly Gln Leu Gln Arg Pro Thr Gly Val Ala Val His Pro Ser
530 535 540
Gly Asp Ile Ile Ile Ala Asp Tyr Asp Asn Lys Trp Val Ser Ile Phe
545 550 555 560
Ser Ser Asp Gly Lys Phe Lys Thr Lys Ile Gly Ser Gly Lys Leu Met
565 570 575
Gly Pro Lys Gly Val Ser Val Asp Arg Asn Gly His Ile Ile Val Val
580 585 590
Asp Asn Lys Ala Cys Cys Val Phe Ile Phe Gln Pro Asn Gly Lys Ile
595 600 605
Val Thr Arg Phe Gly Ser Arg Gly Asn Gly Asp Arg Gln Phe Ala Gly
610 615 620
Pro His Phe Ala Ala Val Asn Ser Asn Asn Glu Ile Ile Ile Thr Asp
625 630 635 640
Phe His Asn His Ser Val Lys Val Phe Asn Gln Glu Gly Glu Phe Met
645 650 655
Leu Lys Phe Gly Ser Asn Gly Glu Gly Asn Gly Gln Phe Asn Ala Pro
660 665 670
Thr Gly Val Ala Val Asp Ser Asn Gly Asn Ile Ile Val Ala Asp Trp
675 680 685
Gly Asn Ser Arg Ile Gln Val Phe Asp Gly Ser Gly Ser Phe Leu Ser
690 695 700
Tyr Ile Asn Thr Ser Ala Asp Pro Leu Tyr Gly Pro Gln Gly Leu Ala
705 710 715 720
Leu Thr Ser Asp Gly His Val Val Val Ala Asp Ser Gly Asn His Cys
725 730 735
Phe Lys Val Tyr Arg Tyr Leu Gln
740
<210>41
<211>1944
<212>DNA
<213>线虫
<220>
<221>CDS
<222>(1)..(1944)
<400>41
atg gcc acg ttt gtt ccc ttt gtt act tgt ctt gat aca ggt ttt tgg 48
Met Ala Thr Phe Val Pro Phe Val Thr Cys Leu Asp Thr Gly Phe Trp
1 5 10 15
aac gaa gtg aac aag aaa aag ctc aat gat tgg aaa ctc gat gag acg 96
Asn Glu Val Asn Lys Lys Lys Leu Asn Asp Trp Lys Leu Asp Glu Thr
20 25 30
cca aag tgt atc tca agt caa tta tcg ctt cat caa acc gaa ggt ttt 144
Pro Lys Cys Ile Ser Ser Gln Leu Ser Leu His Gln Thr Glu Gly Phe
35 40 45
aaa tgt cat cta tcc tta agt tac gac agt ttg agc agt ttg gag agc 192
Lys Cys His Leu Ser Leu Ser Tyr Asp Ser Leu Ser Ser Leu Glu Ser
50 55 60
aca act gga ttg tca atg tcc ggt acc ctt ctt ctg tac aat aca att 240
Thr Thr Gly Leu Ser Met Ser Gly Thr Leu Leu Leu Tyr Asn Thr Ile
65 70 75 80
gaa agt ttc aag atg gtt gac aaa agt gat ttg ata aga agt gaa gca 288
Glu Ser Phe Lys Met Val Asp Lys Ser Asp Leu Ile Arg Ser Glu Ala
85 90 95
gaa aag atc tgg gaa tct atc aca act cga aaa tgg ctc caa aat cct 336
Glu Lys Ile Trp Glu Ser Ile Thr Thr Arg Lys Trp Leu Gln Asn Pro
100 105 110
cgt ctt ctg tcg caa ttc ttc atc atc gct ttt gct gat ttg aaa aaa 384
Arg Leu Leu Ser Gln Phe Phe Ile Ile Ala Phe Ala Asp Leu Lys Lys
115 120 125
ttc aaa tat tat tat tgg aca tgt gtt cct gct ttg gta tat cct agt 432
Phe Lys Tyr Tyr Tyr Trp Thr Cys Val Pro Ala Leu Val Tyr Pro Ser
130 135 140
gaa ata aaa caa gag atc aca cca cta tca tct ctc gga gcc gat cac 480
Glu Ile Lys Gln Glu Ile Thr Pro Leu Ser Ser Leu Gly Ala Asp His
145 150 155 160
aag atc ctg ttc gac ttt tat agg aaa aac aat ttt ccg atc ttc cta 528
Lys Ile Leu Phe Asp Phe Tyr Arg Lys Asn Asn Phe Pro Ile Phe Leu
165 170 175
tac tcc aaa caa tct tca aaa atg ctc gaa ctg tca gaa ttg gaa aac 576
Tyr Ser Lys Gln Ser Ser Lys Met Leu Glu Leu Ser Glu Leu Glu Asn
180 185 190
aac aca aat cct gac gaa ata tgt gtt gtt gtc gct gat cct tct cct 624
Asn Thr Asn Pro Asp Glu Ile Cys Val Val Val Ala Asp Pro Ser Pro
195 200 205
gtt gcg tat tct gca gga tgg atg gtt cgc aac gtt ctt gcc gca gtg 672
Val Ala Tyr Ser Ala Gly Trp Met Val Arg Asn Val Leu Ala Ala Val
210 215 220
gca cat ctt cat cct acg tgg aag cat tgt cat atc atc agt ctt cgt 720
Ala His Leu His Pro Thr Trp Lys His Cys His Ile Ile Ser Leu Arg
225 230 235 240
tca gct gac agt atc gga ata aaa tac aca tgg acc ttg ccg agt gct 768
Ser Ala Asp Ser Ile Gly Ile Lys Tyr Thr Trp Thr Leu Pro Ser Ala
245 250 255
gaa tgc tca gca gat gga gct cag aat gct gtt cca aaa gct gtg gga 816
Glu Cys Ser Ala Asp Gly Ala Gln Asn Ala Val Pro Lys Ala Val Gly
260 265 270
tgg gaa aga aat gca aat gat aag ttg cag ccg att tca gta gac tta 864
Trp Glu Arg Asn Ala Asn Asp Lys Leu Gln Pro Ile Ser Val Asp Leu
275 280 285
agt aaa gag ttc gat cca aaa ata tta atg gaa aga tct gtg gat ctt 912
Ser Lys Glu Phe Asp Pro Lys Ile Leu Met Glu Arg Ser Val Asp Leu
290 295 300
aat tta tca tta atc aaa tgg aga ttg cac cca gat att caa ttg gaa 960
Asn Leu Ser Leu Ile Lys Trp Arg Leu His Pro Asp Ile Gln Leu Glu
305 310 315 320
aga tac tca cag ctg aag gtt ctc att ctt ggt gct gga acg ctt gga 1008
Arg Tyr Ser Gln Leu Lys Val Leu Ile Leu Gly Ala Gly Thr Leu Gly
325 330 335
tgt aac att gcc cgt tgt ctt atc gga tgg gga gtt cgt cac att tcg 1056
Cys Asn Ile Ala Arg Cys Leu Ile Gly Trp Gly Val Arg His Ile Ser
340 345 350
ttt ctt gat aat tca act gtc agc tac aat aac ccc gtt cgc cag agt 1104
Phe Leu Asp Asn Ser Thr Val Ser Tyr Asn Asn Pro Val Arg Gln Ser
355 360 365
ctc tca gaa ttt gaa gat gca cgc ctg ggt cgt gga aaa gcc gaa aca 1152
Leu Ser Glu Phe Glu Asp Ala Arg Leu Gly Arg Gly Lys Ala Glu Thr
370 375 380
gca caa gct gct atc caa cgc att ttc cca tcg att caa gca act gct 1200
Ala Gln Ala Ala Ile Gln Arg Ile Phe Pro Ser Ile Gln Ala Thr Ala
385 390 395 400
cat cgt ctc act gtt cca atg cct gga cat tct atc gat gaa aaa gat 1248
His Arg Leu Thr Val Pro Met Pro Gly His Ser Ile Asp Glu Lys Asp
405 410 415
gta cca gag ctg gaa aaa gat att gca aaa ttg gag caa ctt gtg aaa 1296
Val Pro Glu Leu Glu Lys Asp Ile Ala Lys Leu Glu Gln Leu Val Lys
420 425 430
gat cat gat gtt gtt ttc cta gca tta gat tca agg gaa gct cgc tgg 1344
Asp His Asp Val Val Phe Leu Ala Leu Asp Ser Arg Glu Ala Arg Trp
435 440 445
ctt cca aca gtt ttg gct agt aga cat aag aag att gca att agt gtc 1392
Leu Pro Thr Val Leu Ala Ser Arg His Lys Lys Ile Ala Ile Ser Val
450 455 460
gcg att gga ttc gat acc tac gtc atc att cgg cat gga att ggt tct 1440
Ala Ile Gly Phe Asp Thr Tyr Val Ile Ile Arg His Gly Ile Gly Ser
465 470 475 480
aga agc gaa agt gtt tca gat gtt tca tca tca gat tcc gta cca tac 1488
Arg Ser Glu Ser Val Ser Asp Val Ser Ser Ser Asp Ser Val Pro Tyr
485 490 495
tct cag ctt tct tgc tat ttc tgc agt gat gta act gct cca gga aat 1536
Ser Gln Leu Ser Cys Tyr Phe Cys Ser Asp Val Thr Ala Pro Gly Asn
500 505 510
tct act ttc gat aga aca ttg gac caa cag tgc act gtt gca cga cca 1584
Ser Thr Phe Asp Arg Thr Leu Asp Gln Gln Cys Thr Val Ala Arg Pro
515 520 525
gga aca tct atg att gca tct gga att gcc gtt gaa ctc tta tcg tct 1632
Gly Thr Ser Met Ile Ala Ser Gly Ile Ala Val Glu Leu Leu Ser Ser
530 535 540
gtt tta caa tac cct gat cca ctc aag aca cca gcc agc cac gac gat 1680
Val Leu Gln Tyr Pro Asp Pro Leu Lys Thr Pro Ala Ser His Asp Asp
545 550 555 560
aat aca aca gtc ctt gga gct gct cca cat caa att cgc ggt ttt ctg 1728
Asn Thr Thr Val Leu Gly Ala Ala Pro His Gln Ile Arg Gly Phe Leu
565 570 575
gga aga ttc cag cag att ctt cct tct gta aaa cga ttc gat caa tgt 1776
Gly Arg Phe Gln Gln Ile Leu Pro Ser Val Lys Arg Phe Asp Gln Cys
580 585 590
gtt gct tgt gga gac gct atc gct gca cag ttt cag caa aat ggc tgg 1824
Val Ala Cys Gly Asp Ala Ile Ala Ala Gln Phe Gln Gln Asn Gly Trp
595 600 605
aag ttt gtt cgc gac gtt atg aac tcg cca ggt cgt ctc gaa gaa gtc 1872
Lys Phe Val Arg Asp Val Met Asn Ser Pro Gly Arg Leu Glu Glu Val
610 615 620
acc ggg ctc gac gag ctt cag aac tct gtt aat gct att gat atc gat 1920
Thr Gly Leu Asp Glu Leu Gln Asn Ser Val Asn Ala Ile Asp Ile Asp
625 630 635 640
ttt gag gat gat gaa gat ttc tga 1944
Phe Glu Asp Asp Glu Asp Phe
645
<210>42
<211>647
<212>PRT
<213>线虫
<400>42
Met Ala Thr Phe Val Pro Phe Val Thr Cys Leu Asp Thr Gly Phe Trp
1 5 10 15
Asn Glu Val Asn Lys Lys Lys Leu Asn Asp Trp Lys Leu Asp Glu Thr
20 25 30
Pro Lys Cys Ile Ser Ser Gln Leu Ser Leu His Gln Thr Glu Gly Phe
35 40 45
Lys Cys His Leu Ser Leu Ser Tyr Asp Ser Leu Ser Ser Leu Glu Ser
50 55 60
Thr Thr Gly Leu Ser Met Ser Gly Thr Leu Leu Leu Tyr Asn Thr Ile
65 70 75 80
Glu Ser Phe Lys Met Val Asp Lys Ser Asp Leu Ile Arg Ser Glu Ala
85 90 95
Glu Lys Ile Trp Glu Ser Ile Thr Thr Arg Lys Trp Leu Gln Asn Pro
100 105 110
Arg Leu Leu Ser Gln Phe Phe Ile Ile Ala Phe Ala Asp Leu Lys Lys
115 120 125
Phe Lys Tyr Tyr Tyr Trp Thr Cys Val Pro Ala Leu Val Tyr Pro Ser
130 135 140
Glu Ile Lys Gln Glu Ile Thr Pro Leu Ser Ser Leu Gly Ala Asp His
145 150 155 160
Lys Ile Leu Phe Asp Phe Tyr Arg Lys Asn Asn Phe Pro Ile Phe Leu
165 170 175
Tyr Ser Lys Gln Ser Ser Lys Met Leu Glu Leu Ser Glu Leu Glu Asn
180 185 190
Asn Thr Asn Pro Asp Glu Ile Cys Val Val Val Ala Asp Pro Ser Pro
195 200 205
Val Ala Tyr Ser Ala Gly Trp Met Val Arg Asn Val Leu Ala Ala Val
210 215 220
Ala His Leu His Pro Thr Trp Lys His Cys His Ile Ile Ser Leu Arg
225 230 235 240
Ser Ala Asp Ser Ile Gly Ile Lys Tyr Thr Trp Thr Leu Pro Ser Ala
245 250 255
Glu Cys Ser Ala Asp Gly Ala Gln Asn Ala Val Pro Lys Ala Val Gly
260 265 270
Trp Glu Arg Asn Ala Asn Asp Lys Leu Gln Pro Ile Ser Val Asp Leu
275 280 285
Ser Lys Glu Phe Asp Pro Lys Ile Leu Met Glu Arg Ser Val Asp Leu
290 295 300
Asn Leu Ser Leu Ile Lys Trp Arg Leu His Pro Asp Ile Gln Leu Glu
305 310 315 320
Arg Tyr Ser Gln Leu Lys Val Leu Ile Leu Gly Ala Gly Thr Leu Gly
325 330 335
Cys Asn Ile Ala Arg Cys Leu Ile Gly Trp Gly Val Arg His Ile Ser
340 345 350
Phe Leu Asp Asn Ser Thr Val Ser Tyr Asn Asn Pro Val Arg Gln Ser
355 360 365
Leu Ser Glu Phe Glu Asp Ala Arg Leu Gly Arg Gly Lys Ala Glu Thr
370 375 380
Ala Gln Ala Ala Ile Gln Arg Ile Phe Pro Ser Ile Gln Ala Thr Ala
385 390 395 400
His Arg Leu Thr Val Pro Met Pro Gly His Ser Ile Asp Glu Lys Asp
405 410 415
Val Pro Glu Leu Glu Lys Asp Ile Ala Lys Leu Glu Gln Leu Val Lys
420 425 430
Asp His Asp Val Val Phe Leu Ala Leu Asp Ser Arg Glu Ala Arg Trp
435 440 445
Leu Pro Thr Val Leu Ala Ser Arg His Lys Lys Ile Ala Ile Ser Val
450 455 460
Ala Ile Gly Phe Asp Thr Tyr Val Ile Ile Arg His Gly Ile Gly Ser
465 470 475 480
Arg Ser Glu Ser Val Ser Asp Val Ser Ser Ser Asp Ser Val Pro Tyr
485 490 495
Ser Gln Leu Ser Cys Tyr Phe Cys Ser Asp Val Thr Ala Pro Gly Asn
500 505 510
Ser Thr Phe Asp Arg Thr Leu Asp Gln Gln Cys Thr Val Ala Arg Pro
515 520 525
Gly Thr Ser Met Ile Ala Ser Gly Ile Ala Val Glu Leu Leu Ser Ser
530 535 540
Val Leu Gln Tyr Pro Asp Pro Leu Lys Thr Pro Ala Ser His Asp Asp
545 550 555 560
Asn Thr Thr Val Leu Gly Ala Ala Pro His Gln Ile Arg Gly Phe Leu
565 570 575
Gly Arg Phe Gln Gln Ile Leu Pro Ser Val Lys Arg Phe Asp Gln Cys
580 585 590
Val Ala Cys Gly Asp Ala Ile Ala Ala Gln Phe Gln Gln Asn Gly Trp
595 600 605
Lys Phe Val Arg Asp Val Met Asn Ser Pro Gly Arg Leu Glu Glu Val
610 615 620
Thr Gly Leu Asp Glu Leu Gln Asn Ser Val Asn Ala Ile Asp Ile Asp
625 630 635 640
Phe Glu Asp Asp Glu Asp Phe
645
<210>43
<211>2112
<212>DNA
<213>人
<220>
<221>CDS
<222>(1)..(2112)
<400>43
atg gcg gca gct acg ggg gat cct gga ctc tct aaa ctg cag ttt gcc 48
Met Ala Ala Ala Thr Gly Asp Pro Gly Leu Ser Lys Leu Gln Phe Ala
1 5 10 15
cct ttt agt agt gcc ttg gat gtt ggg ttt tgg cat gag ttg acc cag 96
Pro Phe Ser Ser Ala Leu Asp Val Gly Phe Trp His Glu Leu Thr Gln
20 25 30
aag aag ctg aac gag tat cgg ctg gat gaa gct ccc aag gac att aag 144
Lys Lys Leu Asn Glu Tyr Arg Leu Asp Glu Ala Pro Lys Asp Ile Lys
35 40 45
ggt tat tac tac aat ggt gac tct gct ggg ctg cca gct cgc tta aca 192
Gly Tyr Tyr Tyr Asn Gly Asp Ser Ala Gly Leu Pro Ala Arg Leu Thr
50 55 60
ttg gag ttc agt gct ttt gac atg agt gct ccc acc cca gcc cgt tgc 240
Leu Glu Phe Ser Ala Phe Asp Met Ser Ala Pro Thr Pro Ala Arg Cys
65 70 75 80
tgc cca gct att gga aca ctg tat aac acc aac aca ctc gag tct ttc 288
Cys Pro Ala Ile Gly Thr Leu Tyr Asn Thr Asn Thr Leu Glu Ser Phe
85 90 95
aag act gca gat aag aag ctc ctt ttg gaa caa gca gca aat gag ata 336
Lys Thr Ala Asp Lys Lys Leu Leu Leu Glu Gln Ala Ala Asn Glu Ile
100 105 110
tgg gaa tcc ata aaa tca ggc act gct ctt gaa aac cct gta ctc ctc 384
Trp Glu Ser Ile Lys Ser Gly Thr Ala Leu Glu Asn Pro Val Leu Leu
115 120 125
aac aag ttc ctc ctc ttg aca ttt gca gat cta aag aag tac cac ttc 432
Asn Lys Phe Leu Leu Leu Thr Phe Ala Asp Leu Lys Lys Tyr His Phe
130 135 140
tac tat tgg ttt tgc tat cct gcc ctc tgt ctt cca gag agt tta cct 480
Tyr Tyr Trp Phe Cys Tyr Pro Ala Leu Cys Leu Pro Glu Ser Leu Pro
145 150 155 160
ctc att cag ggg cca gtg ggt ttg gat caa agg ttt tca cta aaa cag 528
Leu Ile Gln Gly Pro Val Gly Leu Asp Gln Arg Phe Ser Leu Lys Gln
165 170 175
att gaa gca cta gag tgt gca tat gat aat ctt tgt caa aca gaa gga 576
Ile Glu Ala Leu Glu Cys Ala Tyr Asp Asn Leu Cys Gln Thr Glu Gly
180 185 190
gtc aca gct ctt cct tac ttc tta atc aag tat gat gag aac atg gtg 624
Val Thr Ala Leu Pro Tyr Phe Leu Ile Lys Tyr Asp Glu Asn Met Val
l95 200 205
ctg gtt tcc ttg ctt aaa cac tac agt gat ttc ttc caa ggt caa agg 672
Leu Val Ser Leu Leu Lys His Tyr Ser Asp Phe Phe Gln Gly Gln Arg
210 215 220
acg aag ata aca att ggt gta tat gat ccc tgt aac tta gcc cag tac 720
Thr Lys Ile Thr Ile Gly Val Tyr Asp Pro Cys Asn Leu Ala Gln Tyr
225 230 235 240
cct gga tgg cct ttg agg aat ttt ttg gtc cta gca gcc cac aga tgg 768
Pro Gly Trp Pro Leu Arg Asn Phe Leu Val Leu Ala Ala His Arg Trp
245 250 255
agt agc agt ttc cag tct gtt gaa gtt gtt tgc ttc cgt gac cgt acc 816
Ser Ser Ser Phe Gln Ser Val Glu Val Val Cys Phe Arg Asp Arg Thr
260 265 270
atg cag ggg gcg aga gac gtt gcc cac agc atc atc ttc gaa gtg aag 864
Met Gln Gly Ala Arg Asp Val Ala His Ser Ile Ile Phe Glu Val Lys
275 280 285
ctt cca gaa atg gca ttt agc cca gat tgt cct aaa gca gtt gga tgg 912
Leu Pro Glu Met Ala Phe Ser Pro Asp Cys Pro Lys Ala Val Gly Trp
290 295 300
gaa aag aac cag aaa gga ggc atg gga cca agg atg gtg aac ctc agt 960
Glu Lys Asn Gln Lys Gly Gly Met Gly Pro Arg Met Val Asn Leu Ser
305 310 315 320
gaa tgt atg gac cct aaa agg tta gct gag tca tca gtg gat cta aat 1008
Glu Cys Met Asp Pro Lys Arg Leu Ala Glu Ser Ser Val Asp Leu Asn
325 330 335
ctc aaa ctg atg tgt tgg aga ttg gtt cct act tta gac ttg gac aag 1056
Leu Lys Leu Met Cys Trp Arg Leu Val Pro Thr Leu Asp Leu Asp Lys
340 345 350
gtt gtg tct gtc aaa tgt ctg ctg ctt gga gcc ggc acc ttg ggt tgc 1104
Val Val Ser Val Lys Cys Leu Leu Leu Gly Ala Gly Thr Leu Gly Cys
355 360 365
aat gta gct agg acg ttg atg ggt tgg ggc gtg aga cac atc aca ttt 1152
Asn Val Ala Arg Thr Leu Met Gly Trp Gly Val Arg His Ile Thr Phe
370 375 380
gtg gac aat gcc aag atc tcc tac tcc aat cct gtg agg cag cct ctc 1200
Val Asp Asn Ala Lys Ile Ser Tyr Ser Asn Pro Val Arg Gln Pro Leu
385 390 395 400
tat gag ttt gaa gat tgc cta ggg ggt ggt aag ccc aag gct ctg gca 1248
Tyr Glu Phe Glu Asp Cys Leu Gly Gly Gly Lys Pro Lys Ala Leu Ala
405 410 415
gca gcg gac cgg ctc cag aaa ata ttc ccc ggt gtg aat gcc aga gga 1296
Ala Ala Asp Arg Leu Gln Lys Ile Phe Pro Gly Val Asn Ala Arg Gly
420 425 430
ttc aac atg agc ata cct atg cct ggg cat cca gtg aac ttc tcc agt 1344
Phe Asn Met Ser Ile Pro Met Pro Gly His Pro Val Asn Phe Ser Ser
435 440 445
gtc act ctg gag caa gcc cgc aga gat gtg gag caa ctg gag cag ctc 1392
Val Thr Leu Glu Gln Ala Arg Arg Asp Val Glu Gln Leu Glu Gln Leu
450 455 460
atc gaa agc cat gat gtc gtc ttc cta ttg atg gac acc agg gag agc 1440
Ile Glu Ser His Asp Val Val Phe Leu Leu Met Asp Thr Arg Glu Ser
465 470 475 480
cgg tgg ctt cct gcc gtc att gct gca agc aag aga aag ctg gtc atc 1488
Arg Trp Leu Pro Ala Val Ile Ala Ala Ser Lys Arg Lys Leu Val Ile
485 490 495
aat gct gct ttg gga ttt gac aca ttt gtt gtc atg aga cat ggt ctg 1536
Asn Ala Ala Leu Gly Phe Asp Thr Phe Val Val Met Arg His Gly Leu
500 505 510
aag aaa cca aag cag caa gga gct ggg gac ttg tgt cca aac cac cct 1584
Lys Lys Pro Lys Gln Gln Gly Ala Gly Asp Leu Cys Pro Asn His Pro
515 520 525
gtg gca tct gct gac ctc ctg ggc tca tcg ctt ttt gcc aac atc cct 1632
Val Ala Ser Ala Asp Leu Leu Gly Ser Ser Leu Phe Ala Asn Ile Pro
530 535 540
ggt tac aag ctt ggc tgc tac ttc tgc aat gat gtg gtg gcc cca gga 1680
Gly Tyr Lys Leu Gly Cys Tyr Phe Cys Asn Asp Val Val Ala Pro Gly
545 550 555 560
gat tca acc aga gac cgg acc ttg gac cag cag tgc act gtg agt cgt 1728
Asp Ser Thr Arg Asp Arg Thr Leu Asp Gln Gln Cys Thr Val Ser Arg
565 570 575
cca gga ctg gcc gtg att gca gga gcc ctg gcc gtg gaa ttg atg gta 1776
Pro Gly Leu Ala Val Ile Ala Gly Ala Leu Ala Val Glu Leu Met Val
580 585 590
tct gtt ttg cag cat cca gaa ggg ggc tat gcc att gcc agc agc agt 1824
Ser Val Leu Gln His Pro Glu Gly Gly Tyr Ala Ile Ala Ser Ser Ser
595 600 605
gac gat cgg atg aat gag cct cca acc tct ctt ggg ctt gtg cct cac 1872
Asp Asp Arg Met Asn Glu Pro Pro Thr Ser Leu Gly Leu Val Pro His
610 615 620
cag atc cgg gga ttt ctt tca cgg ttt gat aat gtc ctt ccc gtc agc 1920
Gln Ile Arg Gly Phe Leu Ser Arg Phe Asp Asn Val Leu Pro Val Ser
625 630 635 640
ctg gca ttt gac aaa tgt aca gct tgt tct tcc aaa gtt ctt gat caa 1968
Leu Ala Phe Asp Lys Cys Thr Ala Cys Ser Ser Lys Val Leu Asp Gln
645 650 655
tat gaa cga gaa gga ttt aac ttc cta gcc aag gtg ttt aat tct tca 2016
Tyr Glu Arg Glu Gly Phe Asn Phe Leu Ala Lys Val Phe Asn Ser Ser
660 665 670
cat tcc ttc tta gaa gac ttg act ggt ctt aca ttg ctg cat caa gaa 2064
His Ser Phe Leu Glu Asp Leu Thr Gly Leu Thr Leu Leu His Gln Glu
675 680 685
acc caa gct gct gag atc tgg gac atg agc gat gat gag acc atc tga 2112
Thr Gln Ala Ala Glu Ile Trp Asp Met Ser Asp Asp Glu Thr Ile
690 695 700
<210>44
<211>703
<212>PRT
<213>人
<400>44
Met Ala Ala Ala Thr Gly Asp Pro Gly Leu Ser Lys Leu Gln Phe Ala
1 5 10 15
Pro Phe Ser Ser Ala Leu Asp Val Gly Phe Trp His Glu Leu Thr Gln
20 25 30
Lys Lys Leu Asn Glu Tyr Arg Leu Asp Glu Ala Pro Lys Asp Ile Lys
35 40 45
Gly Tyr Tyr Tyr Asn Gly Asp Ser Ala Gly Leu Pro Ala Arg Leu Thr
50 55 60
Leu Glu Phe Ser Ala Phe Asp Met Ser Ala Pro Thr Pro Ala Arg Cys
65 70 75 80
Cys Pro Ala Ile Gly Thr Leu Tyr Asn Thr Asn Thr Leu Glu Ser Phe
85 90 95
Lys Thr Ala Asp Lys Lys Leu Leu Leu Glu Gln Ala Ala Asn Glu Ile
100 105 110
Trp Glu Ser Ile Lys Ser Gly Thr Ala Leu Glu Asn Pro Val Leu Leu
115 120 125
Asn Lys Phe Leu Leu Leu Thr Phe Ala Asp Leu Lys Lys Tyr His Phe
130 135 140
Tyr Tyr Trp Phe Cys Tyr Pro Ala Leu Cys Leu Pro Glu Ser Leu Pro
145 150 155 160
Leu Ile Gln Gly Pro Val Gly Leu Asp Gln Arg Phe Ser Leu Lys Gln
165 170 175
Ile Glu Ala Leu Glu Cys Ala Tyr Asp Asn Leu Cys Gln Thr Glu Gly
180 185 190
Val Thr Ala Leu Pro Tyr Phe Leu Ile Lys Tyr Asp Glu Asn Met Val
195 200 205
Leu Val Ser Leu Leu Lys His Tyr Ser Asp Phe Phe Gln Gly Gln Arg
210 215 220
Thr Lys Ile Thr Ile Gly Val Tyr Asp Pro Cys Asn Leu Ala Gln Tyr
225 230 235 240
Pro Gly Trp Pro Leu Arg Asn Phe Leu Val Leu Ala Ala His Arg Trp
245 250 255
Ser Ser Ser Phe Gln Ser Val Glu Val Val Cys Phe Arg Asp Arg Thr
260 265 270
Met Gln Gly Ala Arg Asp Val Ala His Ser Ile Ile Phe Glu Val Lys
275 280 285
Leu Pro Glu Met Ala Phe Ser Pro Asp Cys Pro Lys Ala Val Gly Trp
290 295 300
Glu Lys Asn Gln Lys Gly Gly Met Gly Pro Arg Met Val Asn Leu Ser
305 310 315 320
Glu Cys Met Asp Pro Lys Arg Leu Ala Glu Ser Ser Val Asp Leu Asn
325 330 335
Leu Lys Leu Met Cys Trp Arg Leu Val Pro Thr Leu Asp Leu Asp Lys
340 345 350
Val Val Ser Val Lys Cys Leu Leu Leu Gly Ala Gly Thr Leu Gly Cys
355 360 365
Asn Val Ala Arg Thr Leu Met Gly Trp Gly Val Arg His Ile Thr Phe
370 375 380
Val Asp Asn Ala Lys Ile Ser Tyr Ser Asn Pro Val Arg Gln Pro Leu
385 390 395 400
Tyr Glu Phe Glu Asp Cys Leu Gly Gly Gly Lys Pro Lys Ala Leu Ala
405 410 415
Ala Ala Asp Arg Leu Gln Lys Ile Phe Pro Gly Val Asn Ala Arg Gly
420 425 430
Phe Asn Met Ser Ile Pro Met Pro Gly His Pro Val Asn Phe Ser Ser
435 440 445
Val Thr Leu Glu Gln Ala Arg Arg Asp Val Glu Gln Leu Glu Gln Leu
450 455 460
Ile Glu Ser His Asp Val Val Phe Leu Leu Met Asp Thr Arg Glu Ser
465 470 475 480
Arg Trp Leu Pro Ala Val Ile Ala Ala Ser Lys Arg Lys Leu Val Ile
485 490 495
Asn Ala Ala Leu Gly Phe Asp Thr Phe Val Val Met Arg His Gly Leu
500 505 510
Lys Lys Pro Lys Gln Gln Gly Ala Gly Asp Leu Cys Pro Asn His Pro
515 520 525
Val Ala Ser Ala Asp Leu Leu Gly Ser Ser Leu Phe Ala Asn Ile Pro
530 535 540
Gly Tyr Lys Leu Gly Cys Tyr Phe Cys Asn Asp Val Val Ala Pro Gly
545 550 555 560
Asp Ser Thr Arg Asp Arg Thr Leu Asp Gln Gln Cys Thr Val Ser Arg
565 570 575
Pro Gly Leu Ala Val Ile Ala Gly Ala Leu Ala Val Glu Leu Met Val
580 585 590
Ser Val Leu Gln His Pro Glu Gly Gly Tyr Ala Ile Ala Ser Ser Ser
595 600 605
Asp Asp Arg Met Asn Glu Pro Pro Thr Ser Leu Gly Leu Val Pro His
610 615 620
Gln Ile Arg Gly Phe Leu Ser Arg Phe Asp Asn Val Leu Pro Val Ser
625 630 635 640
Leu Ala Phe Asp Lys Cys Thr Ala Cys Ser Ser Lys Val Leu Asp Gln
645 650 655
Tyr Glu Arg Glu Gly Phe Asn Phe Leu Ala Lys Val Phe Asn Ser Ser
660 665 670
His Ser Phe Leu Glu Asp Leu Thr Gly Leu Thr Leu Leu His Gln Glu
675 680 685
Thr Gln Ala Ala Glu Ile Trp Asp Met Ser Asp Asp Glu Thr Ile
690 695 700
<210>45
<211>288
<212>DNA
<213>线虫
<220>
<221>CDS
<222>(1)..(288)
<400>45
atg tct ttg gtg cca gct tca ttc tat caa aat gtg gat att att cga 48
Met Ser Leu Val Pro Ala Ser Phe Tyr Gln Asn Val Asp Ile Ile Arg
1 5 10 15
gat gtg aag ttt aat atg aag cca acg tgt tcg att tgt atg gaa gaa 96
Asp Val Lys Phe Asn Met Lys Pro Thr Cys Ser Ile Cys Met Glu Glu
20 25 30
ttc gat gca aat tct cat att ccg aag gtt ctc att tgt ggc cac tcg 144
Phe Asp Ala Asn Ser His Ile Pro Lys Val Leu Ile Cys Gly His Ser
35 40 45
ttt tgc att att tgc atc gaa aaa cat ttg aga tca tca aat ctc aca 192
Phe Cys Ile Ile Cys Ile Glu Lys His Leu Arg Ser Ser Asn Leu Thr
50 55 60
ttc tgg cga tgg gga tgt ttt cag tca tta tac atg ctc tac ttg ccg 240
Phe Trp Arg Trp Gly Cys Phe Gln Ser Leu Tyr Met Leu Tyr Leu Pro
65 70 75 80
cac aac gat gga aat tcc tgt caa cgg agc agc tgg att ttc cac taa 288
His Asn Asp Gly Asn Ser Cys Gln Arg Ser Ser Trp Ile Phe His
85 90 95
<210>46
<211>95
<212>PRT
<213>线虫
<400>46
Met Ser Leu Val Pro Ala Ser Phe Tyr Gln Asn Val Asp Ile Ile Arg
1 5 10 15
Asp Val Lys Phe Asn Met Lys Pro Thr Cys Ser Ile Cys Met Glu Glu
20 25 30
Phe Asp Ala Asn Ser His Ile Pro Lys Val Leu Ile Cys Gly His Ser
35 40 45
Phe Cys Ile Ile Cys Ile Glu Lys His Leu Arg Ser Ser Asn Leu Thr
50 55 60
Phe Trp Arg Trp Gly Cys Phe Gln Ser Leu Tyr Met Leu Tyr Leu Pro
65 70 75 80
His Asn Asp Gly Asn Ser Cys Gln Arg Ser Ser Trp Ile Phe His
85 90 95
<210>47
<211>1962
<212>DNA
<213>人
<220>
<221>CDS
<222>(1)..(1962)
<400>47
atg gct gca gca gca gct tct cac ctg aac ctg gat gcc ctc cgg gaa 48
Met Ala Ala Ala Ala Ala Ser His Leu Asn Leu Asp Ala Leu Arg Glu
1 5 10 15
gtg cta gaa tgc ccc atc tgc atg gag tcc ttc aca gaa gag cag ctg 96
Val Leu Glu Cys Pro Ile Cys Met Glu Ser Phe Thr Glu Glu Gln Leu
20 25 30
cgt ccc aag ctt ctg cac tgt ggc cat acc atc tgc cgc cag tgc ctg 144
Arg Pro Lys Leu Leu His Cys Gly His Thr Ile Cys Arg Gln Cys Leu
35 40 45
gag aag cta ttg gcc agt agc atc aat ggt gtc cgc tgt ccc ttt tgc 192
Glu Lys Leu Leu Ala Ser Ser Ile Asn Gly Val Arg Cys Pro Phe Cys
50 55 60
agc aag att acc cgc ata acc agc ttg acc cag ctg aca gac aat ctg 240
Ser Lys Ile Thr Arg Ile Thr Ser Leu Thr Gln Leu Thr Asp Asn Leu
65 70 75 80
aca gtg cta aag atc att gat aca gct ggg ctc agc gag gct gtg ggg 288
Thr Val Leu Lys Ile Ile Asp Thr Ala Gly Leu Ser Glu Ala Val Gly
85 90 95
ctg ctc atg tgt cgg tcc tgt ggg cgg cgt ctg ccc cgg caa ttc tgc 336
Leu Leu Met Cys Arg Ser Cys Gly Arg Arg Leu Pro Arg Gln Phe Cys
100 105 110
cgg agc tgt ggt ttg gtg tta tgt gag ccc tgc cgg gag gca gac cat 384
Arg Ser Cys Gly Leu Val Leu Cys Glu Pro Cys Arg Glu Ala Asp His
115 120 125
cag cct cct ggc cac tgt aca ctc cct gtc aaa gaa gca gct gag gag 432
Gln Pro Pro Gly His Cys Thr Leu Pro Val Lys Glu Ala Ala Glu Glu
130 135 140
cgg cgt cgg gac ttt gga gag aag tta act cgt ctg cgg gaa ctt atg 480
Arg Arg Arg Asp Phe Gly Glu Lys Leu Thr Arg Leu Arg Glu Leu Met
145 150 155 160
ggg gag ctg cag cgg cgg aag gca gcc ttg gaa ggt gtc tcc aag gac 528
Gly Glu Leu Gln Arg Arg Lys Ala Ala Leu Glu Gly Val Ser Lys Asp
165 170 175
ctt cag gca agg tat aaa gca gtt ctc cag gag tat ggg cat gag gag 576
Leu Gln Ala Arg Tyr Lys Ala Val Leu Gln Glu Tyr Gly His Glu Glu
180 185 190
cgc agg gtc cag gat gag ctg gct cgc tct cgg aag ttc ttc aca ggc 624
Arg Arg Val Gln Asp Glu Leu Ala Arg Ser Arg Lys Phe Phe Thr Gly
195 200 205
tct ttg gct gaa gtt gag aag tcc aat agt caa gtg gta gag gag cag 672
Ser Leu Ala Glu Val Glu Lys Ser Asn Ser Gln Val Val Glu Glu Gln
210 215 220
agt tac ctg ctt aac att gca gag gtg cag gct gtg tct cgc tgt gac 720
Ser Tyr Leu Leu Asn Ile Ala Glu Val Gln Ala Val Ser Arg Cys Asp
225 230 235 240
tac ttc ctg gcc aag atc aag cag gca gat gta gca cta ctg gag gag 768
Tyr Phe Leu Ala Lys Ile Lys Gln Ala Asp Val Ala Leu Leu Glu Glu
245 250 255
aca gct gat gag gag gag cca gag ctc act gcc agc ttg cct cgg gag 816
Thr Ala Asp Glu Glu Glu Pro Glu Leu Thr Ala Ser Leu Pro Arg Glu
260 265 270
ctc acc ctg caa gat gtg gag ctc ctt aag gta ggt cat gtt ggc ccc 864
Leu Thr Leu Gln Asp Val Glu Leu Leu Lys Val Gly His Val Gly Pro
275 280 285
ctc caa att gga caa gct gtt aag aag ccc cgg aca gtt aac gtg gaa 912
Leu Gln Ile Gly Gln Ala Val Lys Lys Pro Arg Thr Val Asn Val Glu
290 295 300
gat tcc tgg gcc atg gag gcc aca gcg tct gct gcc tct acc tct gtt 960
Asp Ser Trp Ala Met Glu Ala Thr Ala Ser Ala Ala Ser Thr Ser Val
305 310 315 320
act ttt aga gag atg gac atg agc ccg gag gaa gtg gtt gcc agc cct 1008
Thr Phe Arg Glu Met Asp Met Ser Pro Glu Glu Val Val Ala Ser Pro
325 330 335
agg gcc tca cct gct aaa cag cgg ggt cct gag gca gcc tcc aat atc 1056
Arg Ala Ser Pro Ala Lys Gln Arg Gly Pro Glu Ala Ala Ser Asn Ile
340 345 350
cag cag tgc ctc ttt ctc aag aag atg ggg gcc aaa ggc agc act cca 1104
Gln Gln Cys Leu Phe Leu Lys Lys Met Gly Ala Lys Gly Ser Thr Pro
355 360 365
gga atg ttc aat ctt cca gtc agt ctc tac gtg acc agt caa ggt gaa 1152
Gly Met Phe Asn Leu Pro Val Ser Leu Tyr Val Thr Ser Gln Gly Glu
370 375 380
gta cta gtc gct gac cgt ggt aac tat cgt ata caa gtc ttt acc cgc 1200
Val Leu Val Ala Asp Arg Gly Asn Tyr Arg Ile Gln Val Phe Thr Arg
385 390 395 400
aaa ggc ttt ttg aag gaa atc cgc cgc agc ccc agt ggc att gat agc 1248
Lys Gly Phe Leu Lys Glu Ile Arg Arg Ser Pro Ser Gly Ile Asp Ser
405 410 415
ttt gtg cta agc ttc ctt ggg gca gat cta ccc aac ctc act cct ctc 1296
Phe Val Leu Ser Phe Leu Gly Ala Asp Leu Pro Asn Leu Thr Pro Leu
420 425 430
tca gtg gca atg aac tgc cag ggg ctg att ggt gtg act gac agc tat 1344
Ser Val Ala Met Asn Cys Gln Gly Leu Ile Gly Val Thr Asp Ser Tyr
435 440 445
gat aac tcc ctc aag gta tat acc ttg gat ggc cac tgc gtg gcc tgt 1392
Asp Asn Ser Leu Lys Val Tyr Thr Leu Asp Gly His Cys Val Ala Cys
450 455 460
cac agg agc cag ctg agc aaa cca tgg ggt atc aca gcc ttg cca tct 1440
His Arg Ser Gln Leu Ser Lys Pro Trp Gly Ile Thr Ala Leu Pro Ser
465 470 475 480
ggc cag ttt gta gta acc gat gtg gaa ggt gga aag ctt tgg tgt ttc 1488
Gly Gln Phe Val Val Thr Asp Val Glu Gly Gly Lys Leu Trp Cys Phe
485 490 495
aca gtt gat cga gga tca ggg gtg gtc aaa tac agc tgc cta tgt agt 1536
Thr Val Asp Arg Gly Ser Gly Val Val Lys Tyr Ser Cys Leu Cys Ser
500 505 510
gct gtg cgg ccc aaa ttt gtc acc tgt gat gct gag ggc acc gtc tac 1584
Ala Val Arg Pro Lys Phe Val Thr Cys Asp Ala Glu Gly Thr Val Tyr
515 520 525
ttc acc cag ggc tta ggc ctc aat ctg gag aat cgg cag aat gag cac 1632
Phe Thr Gln Gly Leu Gly Leu Asn Leu Glu Asn Arg Gln Asn Glu His
530 535 540
cac ctg gag ggt ggc ttt tcc att ggc tct gta ggc cct gat ggg cag 1680
His Leu Glu Gly Gly Phe Ser Ile Gly Ser Val Gly Pro Asp Gly Gln
545 550 555 560
ctg ggt cgc cag att agc cac ttc ttc tcg gag aat gag gat ttc cgc 1728
Leu Gly Arg Gln Ile Ser His Phe Phe Ser Glu Asn Glu Asp Phe Arg
565 570 575
tgc att gct ggc atg tgt gtg gat gct cgt ggt gat ctc atc gtg gct 1776
Cys Ile Ala Gly Met Cys Val Asp Ala Arg Gly Asp Leu Ile Val Ala
580 585 590
gac agt agt cgc aag gaa att ctc cat ttt cct aag ggt ggg ggc tat 1824
Asp Ser Ser Arg Lys Glu Ile Leu His Phe Pro Lys Gly Gly Gly Tyr
595 600 605
agt gtc ctt att cga gag gga ctt acc tgt ccg gtg ggc ata gcc cta 1872
Ser Val Leu Ile Arg Glu Gly Leu Thr Cys Pro Val Gly Ile Ala Leu
610 615 620
act cct aag ggg cag ctg ctg gtc ttg gac tgt tgg gat cat tgc atc 1920
Thr Pro Lys Gly Gln Leu Leu Val Leu Asp Cys Trp Asp His Cys Ile
625 630 635 640
aag atc tac agc tac cat ctg aga aga tat tcc acc cca tag 1962
Lys Ile Tyr Ser Tyr His Leu Arg Arg Tyr Ser Thr Pro
645 650
<210>48
<211>653
<212>PRT
<213>人
<400>48
Met Ala Ala Ala Ala Ala Ser His Leu Asn Leu Asp Ala Leu Arg Glu
1 5 10 15
Val Leu Glu Cys Pro Ile Cys Met Glu Ser Phe Thr Glu Glu Gln Leu
20 25 30
Arg Pro Lys Leu Leu His Cys Gly His Thr Ile Cys Arg Gln Cys Leu
35 40 45
Glu Lys Leu Leu Ala Ser Ser Ile Asn Gly Val Arg Cys Pro Phe Cys
50 55 60
Ser Lys Ile Thr Arg Ile Thr Ser Leu Thr Gln Leu Thr Asp Asn Leu
65 70 75 80
Thr Val Leu Lys Ile Ile Asp Thr Ala Gly Leu Ser Glu Ala Val Gly
85 90 95
Leu Leu Met Cys Arg Ser Cys Gly Arg Arg Leu Pro Arg Gln Phe Cys
100 105 110
Arg Ser Cys Gly Leu Val Leu Cys Glu Pro Cys Arg Glu Ala Asp His
115 120 125
Gln Pro Pro Gly His Cys Thr Leu Pro Val Lys Glu Ala Ala Glu Glu
130 135 140
Arg Arg Arg Asp Phe Gly Glu Lys Leu Thr Arg Leu Arg Glu Leu Met
145 150 155 160
Gly Glu Leu Gln Arg Arg Lys Ala Ala Leu Glu Gly Val Ser Lys Asp
165 170 175
Leu Gln Ala Arg Tyr Lys Ala Val Leu Gln Glu Tyr Gly His Glu Glu
180 185 190
Arg Arg Val Gln Asp Glu Leu Ala Arg Ser Arg Lys Phe Phe Thr Gly
195 200 205
Ser Leu Ala Glu Val Glu Lys Ser Asn Ser Gln Val Val Glu Glu Gln
210 215 220
Ser Tyr Leu Leu Asn Ile Ala Glu Val Gln Ala Val Ser Arg Cys Asp
225 230 235 240
Tyr Phe Leu Ala Lys Ile Lys Gln Ala Asp Val Ala Leu Leu Glu Glu
245 250 255
Thr Ala Asp Glu Glu Glu Pro Glu Leu Thr Ala Ser Leu Pro Arg Glu
260 265 270
Leu Thr Leu Gln Asp Val Glu Leu Leu Lys Val Gly His Val Gly Pro
275 280 285
Leu Gln Ile Gly Gln Ala Val Lys Lys Pro Arg Thr Val Asn Val Glu
290 295 300
Asp Ser Trp Ala Met Glu Ala Thr Ala Ser Ala Ala Ser Thr Ser Val
305 310 315 320
Thr Phe Arg Glu Met Asp Met Ser Pro Glu Glu Val Val Ala Ser Pro
325 330 335
Arg Ala Ser Pro Ala Lys Gln Arg Gly Pro Glu Ala Ala Ser Asn Ile
340 345 350
Gln Gln Cys Leu Phe Leu Lys Lys Met Gly Ala Lys Gly Ser Thr Pro
355 360 365
Gly Met Phe Asn Leu Pro Val Ser Leu Tyr Val Thr Ser Gln Gly Glu
370 375 380
Val Leu Val Ala Asp Arg Gly Asn Tyr Arg Ile Gln Val Phe Thr Arg
385 390 395 400
Lys Gly Phe Leu Lys Glu Ile Arg Arg Ser Pro Ser Gly Ile Asp Ser
405 410 415
Phe Val Leu Ser Phe Leu Gly Ala Asp Leu Pro Asn Leu Thr Pro Leu
420 425 430
Ser Val Ala Met Asn Cys Gln Gly Leu Ile Gly Val Thr Asp Ser Tyr
435 440 445
Asp Asn Ser Leu Lys Val Tyr Thr Leu Asp Gly His Cys Val Ala Cys
450 455 460
His Arg Ser Gln Leu Ser Lys Pro Trp Gly Ile Thr Ala Leu Pro Ser
465 470 475 480
Gly Gln Phe Val Val Thr Asp Val Glu Gly Gly Lys Leu Trp Cys Phe
485 490 495
Thr Val Asp Arg Gly Ser Gly Val Val Lys Tyr Ser Cys Leu Cys Ser
500 505 510
Ala Val Arg Pro Lys Phe Val Thr Cys Asp Ala Glu Gly Thr Val Tyr
515 520 525
Phe Thr Gln Gly Leu Gly Leu Asn Leu Glu Asn Arg Gln Asn Glu His
530 535 540
His Leu Glu Gly Gly Phe Ser Ile Gly Ser Val Gly Pro Asp Gly Gln
545 550 555 560
Leu Gly Arg Gln Ile Ser His Phe Phe Ser Glu Asn Glu Asp Phe Arg
565 570 575
Cys Ile Ala Gly Met Cys Val Asp Ala Arg Gly Asp Leu Ile Val Ala
580 585 590
Asp Ser Ser Arg Lys Glu Ile Leu His Phe Pro Lys Gly Gly Gly Tyr
595 600 605
Ser Val Leu Ile Arg Glu Gly Leu Thr Cys Pro Val Gly Ile Ala Leu
610 615 620
Thr Pro Lys Gly Gln Leu Leu Val Leu Asp Cys Trp Asp His Cys Ile
625 630 635 640
Lys Ile Tyr Ser Tyr His Leu Arg Arg Tyr Ser Thr Pro
645 650
<210>49
<211>1125
<212>DNA
<213>线虫
<220>
<221>CDS
<222>(1)..(1125)
<400>49
atg ggg caa gcg aag ttg cgg ctg acg cgt tat tgg atg ctg gcg cgt 48
Met Gly Gln Ala Lys Leu Arg Leu Thr Arg Tyr Trp Met Leu Ala Arg
1 5 10 15
ttc gcg acc agc gtt ggt ttt atc gag aat ttt ctc tgc agt aca aag 96
Phe Ala Thr Ser Val Gly Phe Ile Glu Asn Phe Leu Cys Ser Thr Lys
20 25 30
tcc caa att cgg tgg ttt ttt atc gat ttg acg cgc gtt tgc tca att 144
Ser Gln Ile Arg Trp Phe Phe Ile Asp Leu Thr Arg Val Cys Ser Ile
35 40 45
tct cga ttt tcc gcg ttt ttt att cag ttc tca tta att aac gtt cga 192
Ser Arg Phe Ser Ala Phe Phe Ile Gln Phe Ser Leu Ile Asn Val Arg
50 55 60
tgc ttg ttc aca aaa ttc agt ttt tgt ttt cac ttg ctc gtt ggt gtc 240
Cys Leu Phe Thr Lys Phe Ser Phe Cys Phe His Leu Leu Val Gly Val
65 70 75 80
gtt cgt tgt aat atg ttt gga ggt gga agt agt ggt ccc gtg gac acc 288
Val Arg Cys Asn Met Phe Gly Gly Gly Ser Ser Gly Pro Val Asp Thr
85 90 95
act tta tac aca aca ctc aat gtg aga cca gac gct tcg cag gcc gac 336
Thr Leu Tyr Thr Thr Leu Asn Val Arg Pro Asp Ala Ser Gln Ala Asp
100 105 110
att aag aaa tct tac ttc aaa ctt gct aaa gaa tac cat cca gat aaa 384
Ile Lys Lys Ser Tyr Phe Lys Leu Ala Lys Glu Tyr His Pro Asp Lys
115 120 125
aac ccg gac cat gga gat aaa ttc aaa gag atc agt ttt gcc tat gaa 432
Asn Pro Asp His Gly Asp Lys Phe Lys Glu Ile Ser Phe Ala Tyr Glu
130 135 140
gtt ctt tcg agc cct gaa aaa cga cgc ttg tat gac gcc aga ggt ttg 480
Val Leu Ser Ser Pro Glu Lys Arg Arg Leu Tyr Asp Ala Arg Gly Leu
145 150 155 160
gaa gga gtt caa gga gga gga gct ggt ggt ggt gga gga ggc ttt cct 528
Glu Gly Val Gln Gly Gly Gly Ala Gly Gly Gly Gly Gly Gly Phe Pro
165 170 175
gga ggt ctg ttc tct cac ttc ttc ggc ggt gct ggc ggt gat gac gat 576
Gly Gly Leu Phe Ser His Phe Phe Gly Gly Ala Gly Gly Asp Asp Asp
180 185 190
gac gac gat gat gat atg ggt ggt cat cca ttt ggt ggc ttg ttc ggt 624
Asp Asp Asp Asp Asp Met Gly Gly His Pro Phe Gly Gly Leu Phe Gly
195 200 205
gga atg ggt gga atg gga cga ggt ggc cca cgt cgg cgg aaa ttc caa 672
Gly Met Gly Gly Met Gly Arg Gly Gly Pro Arg Arg Arg Lys Phe Gln
210 215 220
gat act gtt cat ccc ctc aat gtt aca ctc gaa gag ctt tac gtc gga 720
Asp Thr Val His Pro Leu Asn Val Thr Leu Glu Glu Leu Tyr Val Gly
225 230 235 240
aaa aca tca aag ctg aag ctt tcc aaa aag gca ctc tgt aaa act tgc 768
Lys Thr Ser Lys Leu Lys Leu Ser Lys Lys Ala Leu Cys Lys Thr Cys
245 250 255
gaa ggg tca ggt gga aag aag gga gaa aaa tat aag tgt gat gca tgc 816
Glu Gly Ser Gly Gly Lys Lys Gly Glu Lys Tyr Lys Cys Asp Ala Cys
260 265 270
cgt ggt cgt gga gtg aag acg atc gtt cag caa att ggc ccc gga atg 864
Arg Gly Arg Gly Val Lys Thr Ile Val Gln Gln Ile Gly Pro Gly Met
275 280 285
ctc caa caa atg cag gtt cac tgt gat gct tgt aag ggt tct gga ggc 912
Leu Gln Gln Met Gln Val His Cys Asp Ala Cys Lys Gly Ser Gly Gly
290 295 300
aaa gtt cca gca ggt gat aag tgc aaa gga tgc cat gga gaa aag tac 960
Lys Val Pro Ala Gly Asp Lys Cys Lys Gly Cys His Gly Glu Lys Tyr
305 310 315 320
gaa aac gtt tcg aaa ata ttg gag gtt cac gtt ctt cct ggc atg aaa 1008
Glu Asn Val Ser Lys Ile Leu Glu Val His Val Leu Pro Gly Met Lys
325 330 335
cat aac gat aaa att aca ttc aaa gga gat gga gac caa tct gac cca 1056
His Asn Asp Lys Ile Thr Phe Lys Gly Asp Gly Asp Gln Ser Asp Pro
340 345 350
gat ggt gag cca gga gat gtt gtc att gtt att caa cag aaa gat cca 1104
Asp Gly Glu Pro Gly Asp Val Val Ile Val Ile Gln Gln Lys Asp Pro
355 360 365
tct ctg ata tgt tct gaa tga 1125
Ser Leu Ile Cys Ser Glu
370
<210>50
<211>374
<212>PRT
<213>线虫
<400>50
Met Gly Gln Ala Lys Leu Arg Leu Thr Arg Tyr Trp Met Leu Ala Arg
1 5 10 15
Phe Ala Thr Ser Val Gly Phe Ile Glu Asn Phe Leu Cys Ser Thr Lys
20 25 30
Ser Gln Ile Arg Trp Phe Phe Ile Asp Leu Thr Arg Val Cys Ser Ile
35 40 45
Ser Arg Phe Ser Ala Phe Phe Ile Gln Phe Ser Leu Ile Asn Val Arg
50 55 60
Cys Leu Phe Thr Lys Phe Ser Phe Cys Phe His Leu Leu Val Gly Val
65 70 75 80
Val Arg Cys Asn Met Phe Gly Gly Gly Ser Ser Gly Pro Val Asp Thr
85 90 95
Thr Leu Tyr Thr Thr Leu Asn Val Arg Pro Asp Ala Ser Gln Ala Asp
100 105 110
Ile Lys Lys Ser Tyr Phe Lys Leu Ala Lys Glu Tyr His Pro Asp Lys
115 120 125
Asn Pro Asp His Gly Asp Lys Phe Lys Glu Ile Ser Phe Ala Tyr Glu
130 135 140
Val Leu Ser Ser Pro Glu Lys Arg Arg Leu Tyr Asp Ala Arg Gly Leu
145 150 155 160
Glu Gly Val Gln Gly Gly Gly Ala Gly Gly Gly Gly Gly Gly Phe Pro
165 170 175
Gly Gly Leu Phe Ser His Phe Phe Gly Gly Ala Gly Gly Asp Asp Asp
180 185 190
Asp Asp Asp Asp Asp Met Gly Gly His Pro Phe Gly Gly Leu Phe Gly
195 200 205
Gly Met Gly Gly Met Gly Arg Gly Gly Pro Arg Arg Arg Lys Phe Gln
210 215 220
Asp Thr Val His Pro Leu Asn Val Thr Leu Glu Glu Leu Tyr Val Gly
225 230 235 240
Lys Thr Ser Lys Leu Lys Leu Ser Lys Lys Ala Leu Cys Lys Thr Cys
245 250 255
Glu Gly Ser Gly Gly Lys Lys Gly Glu Lys Tyr Lys Cys Asp Ala Cys
260 265 270
Arg Gly Arg Gly Val Lys Thr Ile Val Gln Gln Ile Gly Pro Gly Met
275 280 285
Leu Gln Gln Met Gln Val His Cys Asp Ala Cys Lys Gly Ser Gly Gly
290 295 300
Lys Val Pro Ala Gly Asp Lys Cys Lys Gly Cys His Gly Glu Lys Tyr
305 310 315 320
Glu Asn Val Ser Lys Ile Leu Glu Val His Val Leu Pro Gly Met Lys
325 330 335
His Asn Asp Lys Ile Thr Phe Lys Gly Asp Gly Asp Gln Ser Asp Pro
340 345 350
Asp Gly Glu Pro Gly Asp Val Val Ile Val Ile Gln Gln Lys Asp Pro
355 360 365
Ser Leu Ile Cys Ser Glu
370
<210>51
<211>1239
<212>DNA
<213>人
<220>
<221>CDS
<222>(1)..(1239)
<400>51
atg gct aac gtg gct gac acg aag ctg tac gac atc ctg ggc gtc ccg 48
Met Ala Asn Val Ala Asp Thr Lys Leu Tyr Asp Ile Leu Gly Val Pro
1 5 10 15
ccc ggc gcc agc gag aac gag ctg aag aag gca Lac aga aag tta gcc 96
Pro Gly Ala Ser Glu Asn Glu Leu Lys Lys Ala Tyr Arg Lys Leu Ala
20 25 30
aag gaa tat cat cct gat aag aat cca aat gca gga gac aaa ttt aaa 144
Lys Glu Tyr His Pro Asp Lys Asn Pro Asn Ala Gly Asp Lys Phe Lys
35 40 45
gaa ata agt ttt gca tat gaa gta cta tca aat cct gag aag cgt gag 192
Glu Ile Ser Phe Ala Tyr Glu Val Leu Ser Asn Pro Glu Lys Arg Glu
50 55 60
tta tat gac aga tac gga gag caa ggt ctt cgg gaa ggc agc ggc gga 240
Leu Tyr Asp Arg Tyr Gly Glu Gln Gly Leu Arg Glu Gly Ser Gly Gly
65 70 75 80
ggt ggt ggc atg gat gat att ttc tct cac att ttt ggt ggg gga ttg 288
Gly Gly Gly Met Asp Asp Ile Phe Ser His Ile Phe Gly Gly Gly Leu
85 90 95
ttc ggc ttc atg ggc aat cag agt aga agt cga aat ggc aga aga aga 336
Phe Gly Phe Met Gly Asn Gln Ser Arg Ser Arg Asn Gly Arg Arg Arg
100 105 110
gga gag gac atg atg cat cca ctc aaa gta tct tta gaa gat ctg tat 384
Gly Glu Asp Met Met His Pro Leu Lys Val Ser Leu Glu Asp Leu Tyr
115 120 125
aat ggc aag aca acc aaa cta caa ctt agc aag aat gtg ctc tgt agt 432
Asn Gly Lys Thr Thr Lys Leu Gln Leu Ser Lys Asn Val Leu Cys Ser
130 135 140
gca tgc agt ggc caa ggc gga aag tct gga gct gtc caa aag tgt agt 480
Ala Cys Ser Gly Gln Gly Gly Lys Ser Gly Ala Val Gln Lys Cys Ser
145 150 155 160
gct tgt cga ggt cga ggt gtg cgc atc atg atc aga cag ctg gct cca 528
Ala Cys Arg Gly Arg Gly Val Arg Ile Met Ile Arg Gln Leu Ala Pro
165 170 175
ggg atg gta caa cag atg cag tct gtg tgc tct gat tgt aat gga gaa 576
Gly Met Val Gln Gln Met Gln Ser Val Cys Ser Asp Cys Asn Gly Glu
180 185 190
gga gag gta att aat gaa aaa gac cgc tgt aaa aaa tgt gaa ggg aag 624
Gly Glu Val Ile Asn Glu Lys Asp Arg Cys Lys Lys Cys Glu Gly Lys
195 200 205
aag gtg att aaa gaa gtc aag att ctt gaa gtc cac gta gac aaa ggc 672
Lys Val Ile Lys Glu Val Lys Ile Leu Glu Val His Val Asp Lys Gly
210 215 220
atg aaa cat gga cag aga att aca ttc act ggg gaa gca gac cag gcc 720
Met Lys His Gly Gln Arg Ile Thr Phe Thr Gly Glu Ala Asp Gln Ala
225 230 235 240
cca gga gtg gaa ccc gga gac att gtt ctt ttg cta cag gag aaa gaa 768
Pro Gly Val Glu Pro Gly Asp Ile Val Leu Leu Leu Gln Glu Lys Glu
245 250 255
cat gag gta ttt cag aga gat ggg aat gat ttg cac atg aca tat aaa 816
His Glu Val Phe Gln Arg Asp Gly Asn Asp Leu His Met Thr Tyr Lys
260 265 270
ata gga ctt gtt gaa gct cta tgt gga ttt cag ttc aca ttt aag cac 864
Ile Gly Leu Val Glu Ala Leu Cys Gly Phe Gln Phe Thr Phe Lys His
275 280 285
ctt gat gga cgt cag att gtg gtg aaa tac ccc cct ggc aaa gta att 912
Leu Asp Gly Arg Gln Ile Val Val Lys Tyr Pro Pro Gly Lys Val Ile
290 295 300
gaa cca ggg tgt gtt cgt gta gtt cga ggt gaa ggg atg ccg cag tat 960
Glu Pro Gly Cys Val Arg Val Val Arg Gly Glu Gly Met Pro Gln Tyr
305 310 315 320
cgt aat ccc ttt gaa aaa ggt gat ctt tac ata aag ttt gat gtg cag 1008
Arg Asn Pro Phe Glu Lys Gly Asp Leu Tyr Ile Lys Phe Asp Val Gln
325 330 335
ttt cct gaa aac aac tgg atc aac cca gac aag ctt tct gaa cta gaa 1056
Phe Pro Glu Asn Asn Trp Ile Asn Pro Asp Lys Leu Ser Glu Leu Glu
340 345 350
gat ctt ctg cca tct aga ccg gaa gtt cct aac ata att gga gaa aca 1104
Asp Leu Leu Pro Ser Arg Pro Glu Val Pro Asn Ile Ile Gly Glu Thr
355 360 365
gag gag gta gag ctt cag gaa ttt gat agc act cga ggc tca gga ggt 1152
Glu Glu Val Glu Leu Gln Glu Phe Asp Ser Thr Arg Gly Ser Gly Gly
370 375 380
ggt cag agg cgt gaa gcc tat aat gat agc tct gat gaa gaa agc agc 1200
Gly Gln Arg Arg Glu Ala Tyr Asn Asp Ser Ser Asp Glu Glu Ser Ser
385 390 395 400
agc cat cat gga cct gga gtg cag tgt gcc cat cag taa 1239
Ser His His Gly Pro Gly Val Gln Cys Ala His Gln
405 410
<210>52
<211>412
<212>PRT
<213>人
<400>52
Met Ala Asn Val Ala Asp Thr Lys Leu Tyr Asp Ile Leu Gly Val Pro
1 5 10 15
Pro Gly Ala Ser Glu Asn Glu Leu Lys Lys Ala Tyr Arg Lys Leu Ala
20 25 30
Lys Glu Tyr His Pro Asp Lys Asn Pro Asn Ala Gly Asp Lys Phe Lys
35 40 45
Glu Ile Ser Phe Ala Tyr Glu Val Leu Ser Asn Pro Glu Lys Arg Glu
50 55 60
Leu Tyr Asp Arg Tyr Gly Glu Gln Gly Leu Arg Glu Gly Ser Gly Gly
65 70 75 80
Gly Gly Gly Met Asp Asp Ile Phe Ser His Ile Phe Gly Gly Gly Leu
85 90 95
Phe Gly Phe Met Gly Asn Gln Ser Arg Ser Arg Asn Gly Arg Arg Arg
100 105 110
Gly Glu Asp Met Met His Pro Leu Lys Val Ser Leu Glu Asp Leu Tyr
115 120 125
Asn Gly Lys Thr Thr Lys Leu Gln Leu Ser Lys Asn Val Leu Cys Ser
130 135 140
Ala Cys Ser Gly Gln Gly Gly Lys Ser Gly Ala Val Gln Lys Cys Ser
145 150 155 160
Ala Cys Arg Gly Arg Gly Val Arg Ile Met Ile Arg Gln Leu Ala Pro
165 170 175
Gly Met Val Gln Gln Met Gln Ser Val Cys Ser Asp Cys Asn Gly Glu
180 185 190
Gly Glu Val Ile Asn Glu Lys Asp Arg Cys Lys Lys Cys Glu Gly Lys
195 200 205
Lys Val Ile Lys Glu Val Lys Ile Leu Glu Val His Val Asp Lys Gly
210 215 220
Met Lys His Gly Gln Arg Ile Thr Phe Thr Gly Glu Ala Asp Gln Ala
225 230 235 240
Pro Gly Val Glu Pro Gly Asp Ile Val Leu Leu Leu Gln Glu Lys Glu
245 250 255
His Glu Val Phe Gln Arg Asp Gly Asn Asp Leu His Met Thr Tyr Lys
260 265 270
Ile Gly Leu Val Glu Ala Leu Cys Gly Phe Gln Phe Thr Phe Lys His
275 280 285
Leu Asp Gly Arg Gln Ile Val Val Lys Tyr Pro Pro Gly Lys Val Ile
290 295 300
Glu Pro Gly Cys Val Arg Val Val Arg Gly Glu Gly Met Pro Gln Tyr
305 310 315 320
Arg Asn Pro Phe Glu Lys Gly Asp Leu Tyr Ile Lys Phe Asp Val Gln
325 330 335
Phe Pro Glu Asn Asn Trp Ile Asn Pro Asp Lys Leu Ser Glu Leu Glu
340 345 350
Asp Leu Leu Pro Ser Arg Pro Glu Val Pro Asn Ile Ile Gly Glu Thr
355 360 365
Glu Glu Val Glu Leu Gln Glu Phe Asp Ser Thr Arg Gly Ser Gly Gly
370 375 380
Gly Gln Arg Arg Glu Ala Tyr Asn Asp Ser Ser Asp Glu Glu Ser Ser
385 390 395 400
Ser His His Gly Pro Gly Val Gln Cys Ala His Gln
405 410
<210>53
<211>867
<212>DNA
<213>线虫
<220>
<221>CDS
<222>(1)..(867)
<400>53
atg ccc gac ttc acc aac aag caa att ata tta gat gaa aaa tac gag 48
Met Pro Asp Phe Thr Asn Lys Gln Ile Ile Leu Asp Glu Lys Tyr Glu
1 5 10 15
tat atg gat tca gtg gac gcc atg att ggg atg gga gca ttt gga gca 96
Tyr Met Asp Ser Val Asp Ala Met Ile Gly Met Gly Ala Phe Gly Ala
20 25 30
gtg ttc aag ggg agc ttg aag gat tct agc aat tcg att gcc ata aaa 144
Val Phe Lys Gly Ser Leu Lys Asp Ser Ser Asn Ser Ile Ala Ile Lys
35 40 45
agg atg ctc aaa gtg cac gtg aag gag agc gaa ttg aaa atg atc aaa 192
Arg Met Leu Lys Val His Val Lys Glu Ser Glu Leu Lys Met Ile Lys
50 55 60
gaa ctc aac agt gaa tat cta gtc gga gta cta gac att tgc aat ttc 240
Glu Leu Asn Ser Glu Tyr Leu Val Gly Val Leu Asp Ile Cys Asn Phe
65 70 75 80
gac gac ttt ttc tgc tgt tta ata atg gaa ctc tgc gat tgt gat ctt 288
Asp Asp Phe Phe Cys Cys Leu Ile Met Glu Leu Cys Asp Cys Asp Leu
85 90 95
gac cat cac atg cgc aat att tcg gtc aaa gga aga ttg aat ccg tcg 336
Asp His His Met Arg Asn Ile Ser Val Lys Gly Arg Leu Asn Pro Ser
100 105 110
aat ttc agg ctt ctt ctt gac aac att gcc cga gga tac aaa gcg ctt 384
Asn Phe Arg Leu Leu Leu Asp Asn Ile Ala Arg Gly Tyr Lys Ala Leu
115 120 125
tat gag ttg aaa att gta cat cgg gac att aaa ccc caa aac ata ctg 432
Tyr Glu Leu Lys Ile Val His Arg Asp Ile Lys Pro Gln Asn Ile Leu
130 135 140
atc act tat aca gat gca tcg aaa caa att gct tgt gct cgg atc aca 480
Ile Thr Tyr Thr Asp Ala Ser Lys Gln Ile Ala Cys Ala Arg Ile Thr
145 150 155 160
gac ttt gga att tcg aga acc ctt gat aac gag gga gaa gag ctg tgc 528
Asp Phe Gly Ile Ser Arg Thr Leu Asp Asn Glu Gly Glu Glu Leu Cys
165 170 175
aac gtt gcg ggt aca ttt tat tac atg gct cca gaa gtt gga gcg aac 576
Asn Val Ala Gly Thr Phe Tyr Tyr Met Ala Pro Glu Val Gly Ala Asn
180 185 190
ctt tta aaa act tgt cag tat gac tca aaa gtt gat atg tgg agc atc 624
Leu Leu Lys Thr Cys Gln Tyr Asp Ser Lys Val Asp Met Trp Ser Ile
195 200 205
gga tgc ctt ctc tac caa tgc gtt aca gga gag gtc cca ttc gat gag 672
Gly Cys Leu Leu Tyr Gln Cys Val Thr Gly Glu Val Pro Phe Asp Glu
210 215 220
tgc agt ttg tgt aag ctc ttc ctg tat gtg gca ggg gct aac ttc gac 720
Cys Ser Leu Cys Lys Leu Phe Leu Tyr Val Ala Gly Ala Asn Phe Asp
225 230 235 240
gcc tac gac ccg cct gag ctg ccc gac gag ctg agt caa gag gtt tcg 768
Ala Tyr Asp Pro Pro Glu Leu Pro Asp Glu Leu Ser Gln Glu Val Ser
245 250 255
ggg att att caa tca ctg ctg cag ctc gat acc act caa aga tgc aca 816
Gly Ile Ile Gln Ser Leu Leu Gln Leu Asp Thr Thr Gln Arg Cys Thr
260 265 270
cct act cag ttt tat gac aaa gca atc aac tgg agt caa caa ata tgt 864
Pro Thr Gln Phe Tyr Asp Lys Ala Ile Asn Trp Ser Gln Gln Ile Cys
275 280 285
tag 867
<210>54
<211>288
<212>PRT
<213>线虫
<400>54
Met Pro Asp Phe Thr Asn Lys Gln Ile Ile Leu Asp Glu Lys Tyr Glu
1 5 10 15
Tyr Met Asp Ser Val Asp Ala Met Ile Gly Met Gly Ala Phe Gly Ala
20 25 30
Val Phe Lys Gly Ser Leu Lys Asp Ser Ser Asn Ser Ile Ala Ile Lys
35 40 45
Arg Met Leu Lys Val His Val Lys Glu Ser Glu Leu Lys Met Ile Lys
50 55 60
Glu Leu Asn Ser Glu Tyr Leu Val Gly Val Leu Asp Ile Cys Asn Phe
65 70 75 80
Asp Asp Phe Phe Cys Cys Leu Ile Met Glu Leu Cys Asp Cys Asp Leu
85 90 95
Asp His His Met Arg Asn Ile Ser Val Lys Gly Arg Leu Asn Pro Ser
100 105 110
Asn Phe Arg Leu Leu Leu Asp Asn Ile Ala Arg Gly Tyr Lys Ala Leu
115 120 125
Tyr Glu Leu Lys Ile Val His Arg Asp Ile Lys Pro Gln Asn Ile Leu
130 135 140
Ile Thr Tyr Thr Asp Ala Ser Lys Gln Ile Ala Cys Ala Arg Ile Thr
145 150 155 160
Asp Phe Gly Ile Ser Arg Thr Leu Asp Asn Glu Gly Glu Glu Leu Cys
165 170 175
Asn Val Ala Gly Thr Phe Tyr Tyr Met Ala Pro Glu Val Gly Ala Asn
180 185 190
Leu Leu Lys Thr Cys Gln Tyr Asp Ser Lys Val Asp Met Trp Ser Ile
195 200 205
Gly Cys Leu Leu Tyr Gln Cys Val Thr Gly Glu Val Pro Phe Asp Glu
210 215 220
Cys Ser Leu Cys Lys Leu Phe Leu Tyr Val Ala Gly Ala Asn Phe Asp
225 230 235 240
Ala Tyr Asp Pro Pro Glu Leu Pro Asp Glu Leu Ser Gln Glu Val Ser
245 250 255
Gly Ile Ile Gln Ser Leu Leu Gln Leu Asp Thr Thr Gln Arg Cys Thr
260 265 270
Pro Thr Gln Phe Tyr Asp Lys Ala Ile Asn Trp Ser Gln Gln Ile Cys
275 280 285
<210>55
<211>3111
<212>DNA
<213>人
<220>
<221>CDS
<222>(1)..(3111)
<400>55
atg gag gtg gtg ggt gac ttc gag tac agc aag agg gat ctc gtg gga 48
Met Glu Val Val Gly Asp Phe Glu Tyr Ser Lys Arg Asp Leu Val Gly
1 5 10 15
cac ggg gcc ttc gcc gtg gtc ttc cgg ggg cgg cac cgc cag aaa act 96
His Gly Ala Phe Ala Val Val Phe Arg Gly Arg His Arg Gln Lys Thr
20 25 30
gat tgg gag gta gct att aaa agt att aat aaa aag aac ttg tca aaa 144
Asp Trp Glu Val Ala Ile Lys Ser Ile Asn Lys Lys Asn Leu Ser Lys
35 40 45
tca caa ata ctg ctt gga aag gaa att aaa atc tta aag gaa ctt cag 192
Ser Gln Ile Leu Leu Gly Lys Glu Ile Lys Ile Leu Lys Glu Leu Gln
50 55 60
cat gaa aat att gta gca ctc tat gat gtt cag gaa tta ccc aac tct 240
His Glu Asn Ile Val Ala Leu Tyr Asp Val Gln Glu Leu Pro Asn Ser
65 70 75 80
gtc ttt ttg gtg atg gag tat tgc aat ggt gga gac ctc gca gat tat 288
Val Phe Leu Val Met Glu Tyr Cys Asn Gly Gly Asp Leu Ala Asp Tyr
85 90 95
ttg caa gcg aaa ggg act ctc agt gaa gac acg atc aga gtg ttt ctg 336
Leu Gln Ala Lys Gly Thr Leu Ser Glu Asp Thr Ile Arg Val Phe Leu
100 105 110
cat cag att gct gct gcc atg cga atc ctg cac agc aaa gga atc atc 384
His Gln Ile Ala Ala Ala Met Arg Ile Leu His Ser Lys Gly Ile Ile
115 120 125
cac aga gat ctc aaa cca cag aac atc ttg ctg tcc tat gcc aat cgc 432
His Arg Asp Leu Lys Pro Gln Asn Ile Leu Leu Ser Tyr Ala Asn Arg
130 135 140
aga aaa tca agt gtc agt ggt att cgc atc aaa ata gcg gat ttt ggt 480
Arg Lys Ser Ser Val Ser Gly Ile Arg Ile Lys Ile Ala Asp Phe Gly
145 150 155 160
ttt gct cgt tac cta cat agt aac atg atg gct gca aca ctg tgt gga 528
Phe Ala Arg Tyr Leu His Ser Asn Met Met Ala Ala Thr Leu Cys Gly
165 170 175
tcc ccg atg tac atg gct cct gag gtt att atg tct caa cat tat gat 576
Ser Pro Met Tyr Met Ala Pro Glu Val Ile Met Ser Gln His Tyr Asp
180 185 190
gct aag gct gac ttg tgg agc ata gga aca gtg ata tac caa tgc cta 624
Ala Lys Ala Asp Leu Trp Ser Ile Gly Thr Val Ile Tyr Gln Cys Leu
195 200 205
gtt gga aaa cca cct ttt cag gcc aat agt cct caa gac tta agg atg 672
Val Gly Lys Pro Pro Phe Gln Ala Asn Ser Pro Gln Asp Leu Arg Met
210 215 220
ttt tat gaa aaa aac agg agc tta atg cct agt att ccc aga gaa aca 720
Phe Tyr Glu Lys Asn Arg Ser Leu Met Pro Ser Ile Pro Arg Glu Thr
225 230 235 240
tca cct tat ttg gct aat ctc ctt ttg ggt ttg ctt cag aga aac caa 768
Ser Pro Tyr Leu Ala Asn Leu Leu Leu Gly Leu Leu Gln Arg Asn Gln
245 250 255
aaa gat aga atg gac ttt gaa gca ttt ttt agc cat cct ttt ctt gag 816
Lys Asp Arg Met Asp Phe Glu Ala Phe Phe Ser His Pro Phe Leu Glu
260 265 270
caa ggt cca gta aaa aaa tct tgc cca gtt cca gtg ccc atg tat tct 864
Gln Gly Pro Val Lys Lys Ser Cys Pro Val Pro Val Pro Met Tyr Ser
275 280 285
ggt tct gtc tct gga agc tcc tgt ggc agc tct cca tct tgt cgt ttt 912
Gly Ser Val Ser Gly Ser Ser Cys Gly Ser Ser Pro Ser Cys Arg Phe
290 295 300
gct tct cca cca tcc ctt cca gat atg cag cat att cag gaa gaa aac 960
Ala Ser Pro Pro Ser Leu Pro Asp Met Gln His Ile Gln Glu Glu Asn
305 310 315 320
tta tct tcc cca cca ttg ggt cct ccc aac tat cta caa gtt tcc aaa 1008
Leu Ser Ser Pro Pro Leu Gly Pro Pro Asn Tyr Leu Gln Val Ser Lys
325 330 335
gat tct gcc agt act agt agc aag aac tct tct tgt gac acg gat gac 1056
Asp Ser Ma Ser Thr Ser Ser Lys Asn Ser Ser Cys Asp Thr Asp Asp
340 345 350
ttt gtt ttg gtg cca cac aac atc tcg tca gac cac tca tgt gat atg 1104
Phe Val Leu Val Pro His Asn Ile Ser Ser Asp His Ser Cys Asp Met
355 360 365
cca gtg ggg act gct ggc aga cgt gct tca aat gaa ttc ttg gtg tgt 1152
Pro Val Gly Thr Ala Gly Arg Arg Ala Ser Asn Glu Phe Leu Val Cys
370 375 380
gga ggg cag tgt cag cct act gtg tca cct cac agc gaa aca gca cca 1200
Gly Gly Gln Cys Gln Pro Thr Val Ser Pro His Ser Glu Thr Ala Pro
385 390 395 400
att cca gtt cct act caa ata agg aat tat cag cgc ata gag cag aat 1248
Ile Pro Val Pro Thr Gln Ile Arg Asn Tyr Gln Arg Ile Glu Gln Asn
405 410 415
ctt aca tct act gcc agc tca ggc aca aat gta cat ggt tct cca aga 1296
Leu Thr Ser Thr Ala Ser Ser Gly Thr Asn Val His Gly Ser Pro Arg
420 425 430
tct gca gtg gta cga agg tcc aac acc agc ccc atg ggc ttc ctc cgg 1344
Ser Ala Val Val Arg Arg Ser Asn Thr Ser Pro Met Gly Phe Leu Arg
435 440 445
ccg gga tca tgc tcc cca gta cca gca gac aca gca cag aca gtt gga 1392
Pro Gly Ser Cys Ser Pro Val Pro Ala Asp Thr Ala Gln Thr Val Gly
450 455 460
cga agg ctc tcc act ggg tct tct agg cct tac tca cct tcc cct ttg 1440
Arg Arg Leu Ser Thr Gly Ser Ser Arg Pro Tyr Ser Pro Ser Pro Leu
465 470 475 480
gtt ggt acc att cct gag caa ttc agt cag tgc tgc tgt ggg cat cct 1488
Val Gly Thr Ile Pro Glu Gln Phe Ser Gln Cys Cys Cys Gly His Pro
485 490 495
cag ggc cat gac tcc agg agt aga aac tcc tca ggt tct cca gtg cca 1536
Gln Gly His Asp Ser Arg Ser Arg Asn Ser Ser Gly Ser Pro Val Pro
500 505 510
caa gct cag tcc cca cag tct ctc tta tcg ggt gct aga ctg cag agc 1584
Gln Ala Gln Ser Pro Gln Ser Leu Leu Ser Gly Ala Arg Leu Gln Ser
515 520 525
gcc ccc acc ctc act gac atc tat cag aac aag cag aag ctc aga aaa 1632
Ala Pro Thr Leu Thr Asp Ile Tyr Gln Asn Lys Gln Lys Leu Arg Lys
530 535 540
cag cac tct gac ccc gtg tgc cca tcc cat act ggg gct ggg tac agc 1680
Gln His Ser Asp Pro Val Cys Pro Ser His Thr Gly Ala Gly Tyr Ser
545 550 555 560
tac tcg cct cag ccc agt cgg cct ggc agc ctt gga act tct ccc acc 1728
Tyr Ser Pro Gln Pro Ser Arg Pro Gly Ser Leu Gly Thr Ser Pro Thr
565 570 575
aag cac ttg ggg tcc tct cca cgg agt tct gac tgg ttc ttt aaa act 1776
Lys His Leu Gly Ser Ser Pro Arg Ser Ser Asp Trp Phe Phe Lys Thr
580 585 590
cct ttg cca aca atc att ggc tct cct act aag acc aca gct cct ttc 1824
Pro Leu Pro Thr Ile Ile Gly Ser Pro Thr Lys Thr Thr Ala Pro Phe
595 600 605
aaa atc cct aaa act caa gca tct tcc aac ctg tta gcc ttg gtt act 1872
Lys Ile Pro Lys Thr Gln Ala Ser Ser Asn Leu Leu Ala Leu Val Thr
610 615 620
cgt cat ggg cct gct gaa gaa cag tcg aaa gat ggg aat gag cca cgg 1920
Arg His Gly Pro Ala Glu Glu Gln Ser Lys Asp Gly Asn Glu Pro Arg
625 630 635 640
gaa tgt gcc cat tgc ctc tta gtg caa gga agt gag agg cag cgg gcc 1968
Glu Cys Ala His Cys Leu Leu Val Gln Gly Ser Glu Arg Gln Arg Ala
645 650 655
gag cag cag agc aag gca gtg ttt ggc aga tct gtc agt acc ggg aag 2016
Glu Gln Gln Ser Lys Ala Val Phe Gly Arg Ser Val Ser Thr Gly Lys
660 665 670
tta tca gat caa caa gga aag act cct ata tgt cga cat cag ggc agc 2064
Leu Ser Asp Gln Gln Gly Lys Thr Pro Ile Cys Arg His Gln Gly Ser
675 680 685
aca gac agt tta aat aca gaa cga cca atg gat ata gct ccg gca gga 2112
Thr Asp Ser Leu Asn Thr Glu Arg Pro Met Asp Ile Ala Pro Ala Gly
690 695 700
gcc tgt ggt ggt gtt ctg gca cct cct gca ggt aca gca gca agt tcc 2160
Ala Cys Gly Gly Val Leu Ala Pro Pro Ala Gly Thr Ala Ala Ser Ser
705 710 715 720
aag gct gtc ctc ttc act gta ggg tct cct cca cac agt gcg gca gcc 2208
Lys Ala Val Leu Phe Thr Val Gly Ser Pro Pro His Ser Ala Ala Ala
725 730 735
ccc act tgt acc cac atg ttc ctt cga aca aga aca acc tca gtg ggg 2256
Pro Thr Cys Thr His Met Phe Leu Arg Thr Arg Thr Thr Ser Val Gly
740 745 750
ccc agc aac tcc ggg ggc tct ctt tgt gcc atg agt ggc cgc gtg tgc 2304
Pro Ser Asn Ser Gly Gly Ser Leu Cys Ala Met Ser Gly Arg Val Cys
755 760 765
gtg ggg tcc ccg cct ggc cca ggc ttc ggc tct tcc cct cca gga gca 2352
Val Gly Ser Pro Pro Gly Pro Gly Phe Gly Ser Ser Pro Pro Gly Ala
770 775 780
gag gca gct ccc agc ctg aga tac gtg cct tac ggt gct tca ccc ccc 2400
Glu Ala Ala Pro Ser Leu Arg Tyr Val Pro Tyr Gly Ala Ser Pro Pro
785 790 795 800
agc cta gag ggg ctc atc acc ttt gaa gcc cct gaa ctg ccg gag gag 2448
Ser Leu Glu Gly Leu Ile Thr Phe Glu Ala Pro Glu Leu Pro Glu Glu
805 810 815
acg ctg atg gag cgg gaa cac aca gac acc tta cgc cat ctg aat gtg 2496
Thr Leu Met Glu Arg Glu His Thr Asp Thr Leu Arg His Leu Asn Val
820 825 830
atg ctg atg ttc act gag tgt gtg ctg gac ctg aca gcc atg agg gga 2544
Met Leu Met Phe Thr Glu Cys Val Leu Asp Leu Thr Ala Met Arg Gly
835 840 845
gga aac cct gag ctg tgc aca tct gct gtg tcc ttg tac cag atc cag 2592
Gly Asn Pro Glu Leu Cys Thr Ser Ala Val Ser Leu Tyr Gln Ile Gln
850 855 860
gag agt gtg gtg gtg gac cag atc agt cag ctg agc aaa gac tgg ggg 2640
Glu Ser Val Val Val Asp Gln Ile Ser Gln Leu Ser Lys Asp Trp Gly
865 870 875 880
cgg gtg gag cag ctg gtg ttg tac atg aaa gca gca cag ctg ctt gcg 2688
Arg Val Glu Gln Leu Val Leu Tyr Met Lys Ala Ala Gln Leu Leu Ala
885 890 895
gct tct ctg cat ctt gcc aaa gcc cag atc aag tcc ggg aaa ctg agc 2736
Ala Ser Leu His Leu Ala Lys Ala Gln Ile Lys Ser Gly Lys Leu Ser
900 905 910
cca tcc aca gct gtg aaa caa gtt gtc aag aat ctg aac gaa cga tat 2784
Pro Ser Thr Ala Val Lys Gln Val Val Lys Asn Leu Asn Glu Arg Tyr
915 920 925
aaa ttc tgc atc acc atg tgc aag aaa ctt aca gaa aag ctg aat cga 2832
Lys Phe Cys Ile Thr Met Cys Lys Lys Leu Thr Glu Lys Leu Asn Arg
930 935 940
ttc ttc tct gac aaa cag agg ttt att gat gaa atc aac agt gtg act 2880
Phe Phe Ser Asp Lys Gln Arg Phe Ile Asp Glu Ile Asn Ser Val Thr
945 950 955 960
gca gag aaa ctc atc tat aat tgt gct gta gaa atg gtt cag tct gca 2928
Ala Glu Lys Leu Ile Tyr Asn Cys Ala Val Glu Met Val Gln Ser Ala
965 970 975
gcc ctg gat gag atg ttt cag cag acc gaa gat att gtt tat cgc tat 2976
Ala Leu Asp Glu Met Phe Gln Gln Thr Glu Asp Ile Val Tyr Arg Tyr
980 985 990
cat aag gca gcc ctt ctt ttg gaa ggc cta agt agg att cta cag gac 3024
His Lys Ala Ala Leu Leu Leu Glu Gly Leu Ser Arg Ile Leu Gln Asp
995 1000 1005
cct gca gat att gaa aat gtg cat aaa tat aaa tgt agt att gag 3069
Pro Ala Asp Ile Glu Asn Val His Lys Tyr Lys Cys Ser Ile Glu
1010 1015 1020
aga aga ctg tcg gcg ctc tgc cat agc acc gca acc gtg tga 3111
Arg Arg Leu Ser Ala Leu Cys His Ser Thr Ala Thr Val
1025 1030 1035
<210>56
<211>1036
<212>PRT
<213>人
<400>56
Met Glu Val Val Gly Asp Phe Glu Tyr Ser Lys Arg Asp Leu Val Gly
1 5 10 15
His Gly Ala Phe Ala Val Val Phe Arg Gly Arg His Arg Gln Lys Thr
20 25 30
Asp Trp Glu Val Ala Ile Lys Ser Ile Asn Lys Lys Asn Leu Ser Lys
35 40 45
Ser Gln Ile Leu Leu Gly Lys Glu Ile Lys Ile Leu Lys Glu Leu Gln
50 55 60
His Glu Asn Ile Val Ala Leu Tyr Asp Val Gln Glu Leu Pro Asn Ser
65 70 75 80
Val Phe Leu Val Met Glu Tyr Cys Asn Gly Gly Asp Leu Ala Asp Tyr
85 90 95
Leu Gln Ala Lys Gly Thr Leu Ser Glu Asp Thr Ile Arg Val Phe Leu
100 105 110
His Gln Ile Ala Ala Ala Met Arg Ile Leu His Ser Lys Gly Ile Ile
115 120 125
His Arg Asp Leu Lys Pro Gln Asn Ile Leu Leu Ser Tyr Ala Asn Arg
130 135 140
Arg Lys Ser Ser Val Ser Gly Ile Arg Ile Lys Ile Ala Asp Phe Gly
145 150 155 160
Phe Ala Arg Tyr Leu His Ser Asn Met Met Ala Ala Thr Leu Cys Gly
165 170 175
Ser Pro Met Tyr Met Ala Pro Glu Val Ile Met Ser Gln His Tyr Asp
180 185 190
Ala Lys Ala Asp Leu Trp Ser Ile Gly Thr Val Ile Tyr Gln Cys Leu
195 200 205
Val Gly Lys Pro Pro Phe Gln Ala Asn Ser Pro Gln Asp Leu Arg Met
210 215 220
Phe Tyr Glu Lys Asn Arg Ser Leu Met Pro Ser Ile Pro Arg Glu Thr
225 230 235 240
Ser Pro Tyr Leu Ala Asn Leu Leu Leu Gly Leu Leu Gln Arg Asn Gln
245 250 255
Lys Asp Arg Met Asp Phe Glu Ala Phe Phe Ser His Pro Phe Leu Glu
260 265 270
Gln Gly Pro Val Lys Lys Ser Cys Pro Val Pro Val Pro Met Tyr Ser
275 280 285
Gly Ser Val Ser Gly Ser Ser Cys Gly Ser Ser Pro Ser Cys Arg Phe
290 295 300
Ala Ser Pro Pro Ser Leu Pro Asp Met Gln His Ile Gln Glu Glu Asn
305 310 315 320
Leu Ser Ser Pro Pro Leu Gly Pro Pro Asn Tyr Leu Gln Val Ser Lys
325 330 335
Asp Ser Ala Ser Thr Ser Ser Lys Asn Ser Ser Cys Asp Thr Asp Asp
340 345 350
Phe Val Leu Val Pro His Asn Ile Ser Ser Asp His Ser Cys Asp Met
355 360 365
Pro Val Gly Thr Ala Gly Arg Arg Ala Ser Asn Glu Phe Leu Val Cys
370 375 380
Gly Gly Gln Cys Gln Pro Thr Val Ser Pro His Ser Glu Thr Ala Pro
385 390 395 400
Ile Pro Val Pro Thr Gln Ile Arg Asn Tyr Gln Arg Ile Glu Gln Asn
405 410 415
Leu Thr Ser Thr Ala Ser Ser Gly Thr Asn Val His Gly Ser Pro Arg
420 425 430
Ser Ala Val Val Arg Arg Ser Asn Thr Ser Pro Met Gly Phe Leu Arg
435 440 445
Pro Gly Ser Cys Ser Pro Val Pro Ala Asp Thr Ala Gln Thr Val Gly
450 455 460
Arg Arg Leu Ser Thr Gly Ser Ser Arg Pro Tyr Ser Pro Ser Pro Leu
465 470 475 480
Val Gly Thr Ile Pro Glu Gln Phe Ser Gln Cys Cys Cys Gly His Pro
485 490 495
Gln Gly His Asp Ser Arg Ser Arg Asn Ser Ser Gly Ser Pro Val Pro
500 505 510
Gln Ala Gln Ser Pro Gln Ser Leu Leu Ser Gly Ala Arg Leu Gln Ser
515 520 525
Ala Pro Thr Leu Thr Asp Ile Tyr Gln Asn Lys Gln Lys Leu Arg Lys
530 535 540
Gln His Ser Asp Pro Val Cys Pro Ser His Thr Gly Ala Gly Tyr Ser
545 550 555 560
Tyr Ser Pro Gln Pro Ser Arg Pro Gly Ser Leu Gly Thr Ser Pro Thr
565 570 575
Lys His Leu Gly Ser Ser Pro Arg Ser Ser Asp Trp Phe Phe Lys Thr
580 585 590
Pro Leu Pro Thr Ile Ile Gly Ser Pro Thr Lys Thr Thr Ala Pro Phe
595 600 605
Lys Ile Pro Lys Thr Gln Ala Ser Ser Asn Leu Leu Ala Leu Val Thr
610 615 620
Arg His Gly Pro Ala Glu Glu Gln Ser Lys Asp Gly Asn Glu Pro Arg
625 630 635 640
Glu Cys Ala His Cys Leu Leu Val Gln Gly Ser Glu Arg Gln Arg Ala
645 650 655
Glu Gln Gln Ser Lys Ala Val Phe Gly Arg Ser Val Ser Thr Gly Lys
660 665 670
Leu Ser Asp Gln Gln Gly Lys Thr Pro Ile Cys Arg His Gln Gly Ser
675 680 685
Thr Asp Ser Leu Asn Thr Glu Arg Pro Met Asp Ile Ala Pro Ala Gly
690 695 700
Ala Cys Gly Gly Val Leu Ala Pro Pro Ala Gly Thr Ala Ala Ser Ser
705 710 715 720
Lys Ala Val Leu Phe Thr Val Gly Ser Pro Pro His Ser Ala Ala Ala
725 730 735
Pro Thr Cys Thr His Met Phe Leu Arg Thr Arg Thr Thr Ser Val Gly
740 745 750
Pro Ser Asn Ser Gly Gly Ser Leu Cys Ala Met Ser Gly Arg Val Cys
755 760 765
Val Gly Ser Pro Pro Gly Pro Gly Phe Gly Ser Ser Pro Pro Gly Ala
770 775 780
Glu Ala Ala Pro Ser Leu Arg Tyr Val Pro Tyr Gly Ala Ser Pro Pro
785 790 795 800
Ser Leu Glu Gly Leu Ile Thr Phe Glu Ala Pro Glu Leu Pro Glu Glu
805 810 815
Thr Leu Met Glu Arg Glu His Thr Asp Thr Leu Arg His Leu Asn Val
820 825 830
Met Leu Met Phe Thr Glu Cys Val Leu Asp Leu Thr Ala Met Arg Gly
835 840 845
Gly Asn Pro Glu Leu Cys Thr Ser Ala Val Ser Leu Tyr Gln Ile Gln
850 855 860
Glu Ser Val Val Val Asp Gln Ile Ser Gln Leu Ser Lys Asp Trp Gly
865 870 875 880
Arg Val Glu Gln Leu Val Leu Tyr Met Lys Ala Ala Gln Leu Leu Ala
885 890 895
Ala Ser Leu His Leu Ala Lys Ala Gln Ile Lys Ser Gly Lys Leu Ser
900 905 910
Pro Ser Thr Ala Val Lys Gln Val Val Lys Asn Leu Asn Glu Arg Tyr
915 920 925
Lys Phe Cys Ile Thr Met Cys Lys Lys Leu Thr Glu Lys Leu Asn Arg
930 935 940
Phe Phe Ser Asp Lys Gln Arg Phe Ile Asp Glu Ile Asn Ser Val Thr
945 950 955 960
Ala Glu Lys Leu Ile Tyr Asn Cys Ala Val Glu Met Val Gln Ser Ala
965 970 975
Ala Leu Asp Glu Met Phe Gln Gln Thr Glu Asp Ile Val Tyr Arg Tyr
980 985 990
His Lys Ala Ala Leu Leu Leu Glu Gly Leu Ser Arg Ile Leu Gln Asp
995 1000 1005
Pro Ala Asp Ile Glu Asn Val His Lys Tyr Lys Cys Ser Ile Glu
1010 1015 1020
Arg Arg Leu Ser Ala Leu Cys His Ser Thr Ala Thr Val
1025 1030 1035
<210>57
<211>2280
<212>DNA
<213>线虫
<220>
<221>CDS
<222>(1)..(2280)
<400>57
atg cca aag tct ata tat ttt tcc cct gac ttt atc cga cag caa tcc 48
Met Pro Lys Ser Ile Tyr Phe Ser Pro Asp Phe Ile Arg Gln Gln Ser
1 5 10 15
ggc cac tgc ttc atc atg gga gag cgg aac ctg gtt ctt tat gag aaa 96
Gly His Cys Phe Ile Met Gly Glu Arg Asn Leu Val Leu Tyr Glu Lys
20 25 30
aga atg ttt caa tac aaa gct tcg agt ctg tac tct gga tcc gaa aga 144
Arg Met Phe Gln Tyr Lys Ala Ser Ser Leu Tyr Ser Gly Ser Glu Arg
35 40 45
gat ggt ttt atc cac tgt tgt tct tgg aat gag aat ctc att gcg ttc 192
Asp Gly Phe lle His Cys Cys Ser Trp Asn Glu Asn Leu Ile Ala Phe
50 55 60
aca aat gat acc gga aca aga gtc tac gaa aga ggc gca gag aga atc 240
Thr Asn Asp Thr Gly Thr Arg Val Tyr Glu Arg Gly Ala Glu Arg Ile
65 70 75 80
atc aca agt gtt cag cca tca cat gac gtg gat cgc gtc cga tca tct 288
Ile Thr Ser Val Gln Pro Ser His Asp Val Asp Arg Val Arg Ser Ser
85 90 95
cgc tca cca ccg aaa cac act tgg atg cct gag aac aac tta gtg att 336
Arg Ser Pro Pro Lys His Thr Trp Met Pro Glu Asn Asn Leu Val Ile
100 105 110
ggt tgg gca gac acg gtt acc atc ctc aaa att cgt gat gat gat gga 384
Gly Trp Ala Asp Thr Val Thr Ile Leu Lys Ile Arg Asp Asp Asp Gly
115 120 125
gta aaa aaa gga gag gtt cat cat att ttc cac gta tca atg ttc att 432
Val Lys Lys Gly Glu Val His His Ile Phe His Val Ser Met Phe Ile
130 135 140
tgt gga atc tcc tac atc ccg gaa agc ggc atc gac aat atg gag ctg 480
Cys Gly Ile Ser Tyr Ile Pro Glu Ser Gly Ile Asp Asn Met Glu Leu
145 150 155 160
ttc cta gtt ggg ttg cag ttg gaa ggg gag gac ttt gat gat tgt gcg 528
Phe Leu Val Gly Leu Gln Leu Glu Gly Glu Asp Phe Asp Asp Cys Ala
165 170 175
tca gtt att tcc act gtg aca aca ttg acc gca ttg gaa agt agt gca 576
Ser Val Ile Ser Thr Val Thr Thr Leu Thr Ala Leu Glu Ser Ser Ala
180 185 190
tgc aca atc ctg aag acg tct gtg atc cgg cca ctt gga ttg aaa gaa 624
Cys Thr Ile Leu Lys Thr Ser Val Ile Arg Pro Leu Gly Leu Lys Glu
195 200 205
ttt gag ctt cag tca gag gat atg att gaa agc gtc aaa ctc tcc aac 672
Phe Glu Leu Gln Ser Glu Asp Met Ile Glu Ser Val Lys Leu Ser Asn
210 215 220
cat act ttg cca tac atg att cac ggt ctt gga att cct tac ctt gcc 720
His Thr Leu Pro Tyr Met Ile His Gly Leu Gly Ile Pro Tyr Leu Ala
225 230 235 240
aca tac ttt ata ttg aca acg aag cac att att atg gcg gta cca tat 768
Thr Tyr Phe Ile Leu Thr Thr Lys His Ile Ile Met Ala Val Pro Tyr
245 250 255
ggc ccg gaa gac ggc att cgt tgg aga ttg aag tat aaa ctc tac gat 816
Gly Pro Glu Asp Gly Ile Arg Trp Arg Leu Lys Tyr Lys Leu Tyr Asp
260 265 270
gaa gcg ttg gat atg gca aag cac aat gcc gac tta ctc tcc aaa act 864
Glu Ala Leu Asp Met Ala Lys His Asn Ala Asp Leu Leu Ser Lys Thr
275 280 285
gat ctc agt ccg aag aaa gtg ggg agg atg att atc gag gga Lac ctg 912
Asp Leu Ser Pro Lys Lys Val Gly Arg Met Ile Ile Glu Gly Tyr Leu
290 295 300
act gga aaa cga gca aga gca gct gct tcc cgc ctt cca ttg atc tgt 960
Thr Gly Lys Arg Ala Arg Ala Ala Ala Ser Arg Leu Pro Leu Ile Cys
305 310 315 320
gga gaa tgc aag gag gag tgg gaa tgg gca gtg aat cag ttt gag gaa 1008
Gly Glu Cys Lys Glu Glu Trp Glu Trp Ala Val Asn Gln Phe Glu Glu
325 330 335
gtc aaa tta tgc act cta cta gcg gag gtc ctg ccc gat ggc act ccg 1056
Val Lys Leu Cys Thr Leu Leu Ala Glu Val Leu Pro Asp Gly Thr Pro
340 345 350
aca ttg gat cca gag tgc tac cag aaa gtt ctt att gct tgt ctg ttc 1104
Thr Leu Asp Pro Glu Cys Tyr Gln Lys Val Leu Ile Ala Cys Leu Phe
355 360 365
aac aat gtg aag cag ttc cgg aaa ttg gta cag acg tgg agt ccg gat 1152
Asn Asn Val Lys Gln Phe Arg Lys Leu Val Gln Thr Trp Ser Pro Asp
370 375 380
ctc tat atg acc agt ttt ata atc gat cgg act caa tgg cgc att caa 1200
Leu Tyr Met Thr Ser Phe Ile Ile Asp Arg Thr Gln Trp Arg Ile Gln
385 390 395 400
caa atc agc aaa tcg ggc aat cta gca gac gtt gac gag act gag cga 1248
Gln Ile Ser Lys Ser Gly Asn Leu Ala Asp Val Asp Glu Thr Glu Arg
405 410 415
gtt ttg atg gac gct ttg gca cat ttg tat ctc tac gag aga aag tac 1296
Val Leu Met Asp Ala Leu Ala His Leu Tyr Leu Tyr Glu Arg Lys Tyr
420 425 430
gag agc gca ctg aaa atc ctt atg tcg tgt caa gat ttt caa att ttc 1344
Glu Ser Ala Leu Lys Ile Leu Met Ser Cys Gln Asp Phe Gln Ile Phe
435 440 445
aat gtt att gac aag cat caa ctc ttc gat ctt gtc aag gat caa atc 1392
Asn Val Ile Asp Lys His Gln Leu Phe Asp Leu Val Lys Asp Gln Ile
450 455 460
acc gaa ctg atg aac atc aac tct gaa cgt gct ctt cgg ctg ttg ctc 1440
Thr Glu Leu Met Asn Ile Asn Ser Glu Arg Ala Leu Arg Leu Leu Leu
465 470 475 480
gac aac gct gat tcg gtg gag cca tca ttt gtg atg gag aaa att ggg 1488
Asp Asn Ala Asp Ser Val Glu Pro Ser Phe Val Met Glu Lys Ile Gly
485 490 495
cga cag ccg aaa ctg caa ctc gcg tat ctc aca aaa ctg atg agc aga 1536
Arg Gln Pro Lys Leu Gln Leu Ala Tyr Leu Thr Lys Leu Met Ser Arg
500 505 510
aac gag gga act gag ttt gct gac aaa gct gtc cag ttg tat gct gaa 1584
Asn Glu Gly Thr Glu Phe Ala Asp Lys Ala Val Gln Leu Tyr Ala Glu
515 520 525
tac gac cag aag aag ctt ctt cca ttt ttg aga aag aat gca aac tac 1632
Tyr Asp Gln Lys Lys Leu Leu Pro Phe Leu Arg Lys Asn Ala Asn Tyr
530 535 540
aat gtg aac aag gca cga aag ttg tgc tcg gat aag gga tat att gaa 1680
Asn Val Asn Lys Ala Arg Lys Leu Cys Ser Asp Lys Gly Tyr Ile Glu
545 550 555 560
gag aca atc tat ctt ctt gcc aaa agt gga aat cat tat gat gct gtg 1728
Glu Thr Ile Tyr Leu Leu Ala Lys Ser Gly Asn His Tyr Asp Ala Val
565 570 575
aaa atg atg gtt cga gag tat cgg aac atg gaa aaa gtc atc gat tac 1776
Lys Met Met Val Arg Glu Tyr Arg Asn Met Glu Lys Val Ile Asp Tyr
580 585 590
tgc aaa gat caa aat gac ccc gat tta tgg att cac ctt cta gga gta 1824
Cys Lys Asp Gln Asn Asp Pro Asp Leu Trp Ile His Leu Leu Gly Val
595 600 605
gtt gcc gag ttt cct gct cat ttt tcg cag ctt atc att gaa gcg tca 1872
Val Ala Glu Phe Pro Ala His Phe Ser Gln Leu Ile Ile Glu Ala Ser
610 615 620
aac tgc ctc gat cct ctc ctg att atg gac aaa cta ccg gac gat tcg 1920
Asn Cys Leu Asp Pro Leu Leu Ile Met Asp Lys Leu Pro Asp Asp Ser
625 630 635 640
gat att cct aac ttg agt gaa gcg ctc gac aaa ctt ctc gtt gac tat 1968
Asp Ile Pro Asn Leu Ser Glu Ala Leu Asp Lys Leu Leu Val Asp Tyr
645 650 655
aca aat cat gca gag ctt cag caa tgt tgc tac gac tca acc ttg aac 2016
Thr Asn His Ala Glu Leu Gln Gln Cys Cys Tyr Asp Ser Thr Leu Asn
660 665 670
gat ctg aat gtt ctc act caa gga ctg ata tcg gca gct gat gaa tca 2064
Asp Leu Asn Val Leu Thr Gln Gly Leu Ile Ser Ala Ala Asp Glu Ser
675 680 685
gtt tcc gtg aac ata gta tcc aga tgt tca tta tgt gct caa atc atc 2112
Val Ser Val Asn Ile Val Ser Arg Cys Ser Leu Cys Ala Gln Ile Ile
690 695 700
atc aat tct aac caa gaa aca aca aaa aag ttt tcg gat ata aaa gtg 2160
Ile Asn Ser Asn Gln Glu Thr Thr Lys Lys Phe Ser Asp Ile Lys Val
705 710 715 720
ttc aaa tgc gga cac att ttt cac ttg gct tgt tct act tct gag atg 2208
Phe Lys Cys Gly His Ile Phe His Leu Ala Cys Ser Thr Ser Glu Met
725 730 735
gaa cgc cgt caa tca att gag gag ggc ctc tgc att gcg tgc tct gat 2256
Glu Arg Arg Gln Ser Ile Glu Glu Gly Leu Cys Ile Ala Cys Ser Asp
740 745 750
caa atc gaa ctc atc aac gtg taa 2280
Gln Ile Glu Leu Ile Asn Val
755
<210>58
<211>759
<212>PRT
<213>线虫
<400>58
Met Pro Lys Ser Ile Tyr Phe Ser Pro Asp Phe Ile Arg Gln Gln Ser
1 5 10 15
Gly His Cys Phe Ile Met Gly Glu Arg Asn Leu Val Leu Tyr Glu Lys
20 25 30
Arg Met Phe Gln Tyr Lys Ala Ser Ser Leu Tyr Ser Gly Ser Glu Arg
35 40 45
Asp Gly Phe Ile His Cys Cys Ser Trp Asn Glu Asn Leu Ile Ala Phe
50 55 60
Thr Asn Asp Thr Gly Thr Arg Val Tyr Glu Arg Gly Ala Glu Arg Ile
65 70 75 80
Ile Thr Ser Val Gln Pro Ser His Asp Val Asp Arg Val Arg Ser Ser
85 90 95
Arg Ser Pro Pro Lys His Thr Trp Met Pro Glu Asn Asn Leu Val Ile
100 105 110
Gly Trp Ala Asp Thr Val Thr Ile Leu Lys Ile Arg Asp Asp Asp Gly
115 120 125
Val Lys Lys Gly Glu Val His His Ile Phe His Val Ser Met Phe Ile
130 135 140
Cys Gly Ile Ser Tyr Ile Pro Glu Ser Gly Ile Asp Asn Met Glu Leu
145 150 155 160
Phe Leu Val Gly Leu Gln Leu Glu Gly Glu Asp Phe Asp Asp Cys Ala
165 170 175
Ser Val Ile Ser Thr Val Thr Thr Leu Thr Ala Leu Glu Ser Ser Ala
180 185 190
Cys Thr Ile Leu Lys Thr Ser Val Ile Arg Pro Leu Gly Leu Lys Glu
195 200 205
Phe Glu Leu Gln Ser Glu Asp Met Ile Glu Ser Val Lys Leu Ser Asn
210 215 220
His Thr Leu Pro Tyr Met Ile His Gly Leu Gly Ile Pro Tyr Leu Ala
225 230 235 240
Thr Tyr Phe Ile Leu Thr Thr Lys His Ile Ile Met Ala Val Pro Tyr
245 250 255
Gly Pro Glu Asp Gly Ile Arg Trp Arg Leu Lys Tyr Lys Leu Tyr Asp
260 265 270
Glu Ala Leu Asp Met Ala Lys His Asn Ala Asp Leu Leu Ser Lys Thr
275 280 285
Asp Leu Ser Pro Lys Lys Val Gly Arg Met Ile Ile Glu Gly Tyr Leu
290 295 300
Thr Gly Lys Arg Ala Arg Ala Ala Ala Ser Arg Leu Pro Leu Ile Cys
305 310 315 320
Gly Glu Cys Lys Glu Glu Trp Glu Trp Ala Val Asn Gln Phe Glu Glu
325 330 335
Val Lys Leu Cys Thr Leu Leu Ala Glu Val Leu Pro Asp Gly Thr Pro
340 345 350
Thr Leu Asp Pro Glu Cys Tyr Gln Lys Val Leu Ile Ala Cys Leu Phe
355 360 365
Asn Asn Val Lys Gln Phe Arg Lys Leu Val Gln Thr Trp Ser Pro Asp
370 375 380
Leu Tyr Met Thr Ser Phe Ile Ile Asp Arg Thr Gln Trp Arg Ile Gln
385 390 395 400
Gln Ile Ser Lys Ser Gly Asn Leu Ala Asp Val Asp Glu Thr Glu Arg
405 410 415
Val Leu Met Asp Ala Leu Ala His Leu Tyr Leu Tyr Glu Arg Lys Tyr
420 425 430
Glu Ser Ala Leu Lys Ile Leu Met Ser Cys Gln Asp Phe Gln Ile Phe
435 440 445
Asn Val Ile Asp Lys His Gln Leu Phe Asp Leu Val Lys Asp Gln Ile
450 455 460
Thr Glu Leu Met Asn Ile Asn Ser Glu Arg Ala Leu Arg Leu Leu Leu
465 470 475 480
Asp Asn Ala Asp Ser Val Glu Pro Ser Phe Val Met Glu Lys Ile Gly
485 490 495
Arg Gln Pro Lys Leu Gln Leu Ala Tyr Leu Thr Lys Leu Met Ser Arg
500 505 510
Asn Glu Gly Thr Glu Phe Ala Asp Lys Ala Val Gln Leu Tyr Ala Glu
515 520 525
Tyr Asp Gln Lys Lys Leu Leu Pro Phe Leu Arg Lys Asn Ala Asn Tyr
530 535 540
Asn Val Asn Lys Ala Arg Lys Leu Cys Ser Asp Lys Gly Tyr Ile Glu
545 550 555 560
Glu Thr Ile Tyr Leu Leu Ala Lys Ser Gly Asn His Tyr Asp Ala Val
565 570 575
Lys Met Met Val Arg Glu Tyr Arg Asn Met Glu Lys Val Ile Asp Tyr
580 585 590
Cys Lys Asp Gln Asn Asp Pro Asp Leu Trp Ile His Leu Leu Gly Val
595 600 605
Val Ala Glu Phe Pro Ala His Phe Ser Gln Leu Ile Ile Glu Ala Ser
610 615 620
Asn Cys Leu Asp Pro Leu Leu Ile Met Asp Lys Leu Pro Asp Asp Ser
625 630 635 640
Asp Ile Pro Asn Leu Ser Glu Ala Leu Asp Lys Leu Leu Val Asp Tyr
645 650 655
Thr Asn His Ala Glu Leu Gln Gln Cys Cys Tyr Asp Ser Thr Leu Asn
660 665 670
Asp Leu Asn Val Leu Thr Gln Gly Leu Ile Ser Ala Ala Asp Glu Ser
675 680 685
Val Ser Val Asn Ile Val Ser Arg Cys Ser Leu Cys Ala Gln Ile Ile
690 695 700
Ile Asn Ser Asn Gln Glu Thr Thr Lys Lys Phe Ser Asp Ile Lys Val
705 710 715 720
Phe Lys Cys Gly His Ile Phe His Leu Ala Cys Ser Thr Ser Glu Met
725 730 735
Glu Arg Arg Gln Ser Ile Glu Glu Gly Leu Cys Ile Ala Cys Ser Asp
740 745 750
Gln Ile Glu Leu Ile Asn Val
755
<210>59
<211>2565
<212>DNA
<213>人
<220>
<221>CDS
<222>(1)..(2565)
<400>59
atg gcg gaa gca gag gag cag gaa act ggg tcc ctt gaa gaa tct aca 48
Met Ala Glu Ala Glu Glu Gln Glu Thr Gly Ser Leu Glu Glu Ser Thr
1 5 10 15
gat gag tct gag gaa gaa gag agc gaa gag gaa ccc aag ctg aag tat 96
Asp Glu Ser Glu Glu Glu Glu Ser Glu Glu Glu Pro Lys Leu Lys Tyr
20 25 30
gaa agg ctt tcc aat ggg gta act gaa ata ctt cag aag gat gca gct 144
Glu Arg Leu Ser Asn Gly Val Thr Glu Ile Leu Gln Lys Asp Ala Ala
35 40 45
agc tgc atg aca gtc cat gac aag ttt ttg gca ttg ggc aca cat tat 192
Ser Cys Met Thr Val His Asp Lys Phe Leu Ala Leu Gly Thr His Tyr
50 55 60
ggc aag gtt tat tta ctt gat gtc cag ggg aac atc act cag aag ttt 240
Gly Lys Val Tyr Leu Leu Asp Val Gln Gly Asn Ile Thr Gln Lys Phe
65 70 75 80
gat gta agt cct gtg aag ata aat cag att agc ttg gat gaa agt gga 288
Asp Val Ser Pro Val Lys Ile Asn Gln Ile Ser Leu Asp Glu Ser Gly
85 90 95
gag cac atg ggt gtg tgt tca gag gat ggc aag gtg cag gta ttt gga 336
Glu His Met Gly Val Cys Ser Glu Asp Gly Lys Val Gln Val Phe Gly
100 105 110
ctg tat tct gga gaa gaa ttt cac gag act ttt gac tgt ccc att aaa 384
Leu Tyr Ser Gly Glu Glu Phe His Glu Thr Phe Asp Cys Pro Ile Lys
115 120 125
att att gct gtg cac cca cat ttc gtg aga tcc agt tgc aag cag ttt 432
Ile Ile Ala Val His Pro His Phe Val Arg Ser Ser Cys Lys Gln Phe
130 135 140
gtg acc gga ggg aag aag ctg cta ctg ttt gaa cgg tct tgg atg aac 480
Val Thr Gly Gly Lys Lys Leu Leu Leu Phe Glu Arg Ser Trp Met Asn
145 150 155 160
aga tgg aag tct gct gtt ctg cat gaa ggg gaa ggg aac ata agg agt 528
Arg Trp Lys Ser Ala Val Leu His Glu Gly Glu Gly Asn Ile Arg Ser
165 170 175
gtg aag tgg aga ggc cat ctg att gct tgg gcc aat aat atg ggt gtg 576
Val Lys Trp Arg Gly His Leu Ile Ala Trp Ala Asn Asn Met Gly Val
180 185 190
aag att ttt gac atc atc tca aag caa aga atc acc aat gtg ccc cgg 624
Lys Ile Phe Asp Ile Ile Ser Lys Gln Arg Ile Thr Asn Val Pro Arg
195 200 205
gat gat ata agt ctt cgc cca gac atg tat ccc tgc agc ctc tgc tgg 672
Asp Asp Ile Ser Leu Arg Pro Asp Met Tyr Pro Cys Ser Leu Cys Trp
210 215 220
aag gac aat gtg aca ctg att att ggc tgg ggg act tct gtc aag gtg 720
Lys Asp Asn Val Thr Leu Ile Ile Gly Trp Gly Thr Ser Val Lys Val
225 230 235 240
tgc tca gtg aag gaa cgg cat gcc agt gaa atg agg gat ttg cca agt 768
Cys Ser Val Lys Glu Arg His Ala Ser Glu Met Arg Asp Leu Pro Ser
245 250 255
cga tat gtt gaa ata gtg tct cag ttt gaa act gaa ttc tac atc agt 816
Arg Tyr Val Glu Ile Val Ser Gln Phe Glu Thr Glu Phe Tyr Ile Ser
260 265 270
gga ctt gca cct ctc tgt gat cag ctt gtt gta ctt tcg tat gta aag 864
Gly Leu Ala Pro Leu Cys Asp Gln Leu Val Val Leu Ser Tyr Val Lys
275 280 285
gag att tca gaa aaa acg gaa aga gaa tac tgt gcc agg cct aga ctg 912
Glu Ile Ser Glu Lys Thr Glu Arg Glu Tyr Cys Ala Arg Pro Arg Leu
290 295 300
gac atc atc cag cca ctt tct gag act tgt gaa gag atc tct tct gat 960
Asp Ile Ile Gln Pro Leu Ser Glu Thr Cys Glu Glu Ile Ser Ser Asp
305 310 315 320
gct ttg aca gtc aga ggc ttt cag gag aat gaa tgt aga gat tat cat 1008
Ala Leu Thr Val Arg Gly Phe Gln Glu Asn Glu Cys Arg Asp Tyr His
325 330 335
tta gaa tac tct gaa ggg gaa tca ctt ttt tac atc gtg agt ccg aga 1056
Leu Glu Tyr Ser Glu Gly Glu Ser Leu Phe Tyr Ile Val Ser Pro Arg
340 345 350
gat gtt gta gtg gcc aag gaa cga gac caa gat gat cac att gac tgg 1104
Asp Val Val Val Ala Lys Glu Arg Asp Gln Asp Asp His Ile Asp Trp
355 360 365
ctc ctt gaa aag aag aaa tat gaa gaa gca ttg atg gca gct gaa att 1152
Leu Leu Glu Lys Lys Lys Tyr Glu Glu Ala Leu Met Ala Ala Glu Ile
370 375 380
agc caa aaa aat att aaa aga cat aag att ctg gat att ggc ttg gca 1200
Ser Gln Lys Asn Ile Lys Arg His Lys Ile Leu Asp Ile Gly Leu Ala
385 390 395 400
tat ata aat cac ctg gtg gag aga gga gac tat gac ata gca gca cgc 1248
Tyr Ile Asn His Leu Val Glu Arg Gly Asp Tyr Asp Ile Ala Ala Arg
405 410 415
aaa tgc cag aaa att ctt ggg aaa aat gca gca ctc tgg gaa tat gaa 1296
Lys Cys Gln Lys Ile Leu Gly Lys Asn Ala Ala Leu Trp Glu Tyr Glu
420 425 430
gtt tat aaa ttt aaa gaa att gga cag ctt aag gct att agt cct tat 1344
Val Tyr Lys Phe Lys Glu Ile Gly Gln Leu Lys Ala Ile Ser Pro Tyr
435 440 445
ttg cca aga ggt gat cca gtt ctg aaa cca ctc atc tat gaa atg atc 1392
Leu Pro Arg Gly Asp Pro Val Leu Lys Pro Leu Ile Tyr Glu Met Ile
450 455 460
tta cat gaa ttt ttg gag agt gat tat gag ggt ttt gcc aca ttg atc 1440
Leu His Glu Phe Leu Glu Ser Asp Tyr Glu Gly Phe Ala Thr Leu Ile
465 470 475 480
cga gaa tgg cct gga gat ctg tat aat aat tca gtc ata gtt caa gca 1488
Arg Glu Trp Pro Gly Asp Leu Tyr Asn Asn Ser Val Ile Val Gln Ala
485 490 495
gtt cgg gat cat ttg aag aaa gat agt cag aac aag act tta ctt aaa 1536
Val Arg Asp His Leu Lys Lys Asp Ser Gln Asn Lys Thr Leu Leu Lys
500 505 510
acc ctg gca gaa ttg tac acc tat gac aag aac tat ggc aat gct ctg 1584
Thr Leu Ala Glu Leu Tyr Thr Tyr Asp Lys Asn Tyr Gly Asn Ala Leu
515 520 525
gaa ata tac tta aca tta aga cat aaa gac gtt ttt cag ttg atc cac 1632
Glu Ile Tyr Leu Thr Leu Arg His Lys Asp Val Phe Gln Leu Ile His
530 535 540
aag cat aat ctt ttc agt tct atc aag gat aaa att gtt tta tta atg 1680
Lys His Asn Leu Phe Ser Ser Ile Lys Asp Lys Ile Val Leu Leu Met
545 550 555 560
gat ttt gat tca gag aaa gct gtt gac atg ctt ttg gac aat gaa gat 1728
Asp Phe Asp Ser Glu Lys Ala Val Asp Met Leu Leu Asp Asn Glu Asp
565 570 575
aaa att tca att aaa aag gta gtg gaa gaa ttg gaa gac aga cca gag 1776
Lys Ile Ser Ile Lys Lys Val Val Glu Glu Leu Glu Asp Arg Pro Glu
580 585 590
cta cag cat gtg tat ttg cat aag ctt ttc aag aga gac cac cat aag 1824
Leu Gln His Val Tyr Leu His Lys Leu Phe Lys Arg Asp His His Lys
595 600 605
ggg cag cgt tac cat gaa aaa cag atc agt ctt tat gct gaa tat gat 1872
Gly Gln Arg Tyr His Glu Lys Gln Ile Ser Leu Tyr Ala Glu Tyr Asp
610 615 620
cga cca aac tta ctt ccc ttt ctc cga gac agt acc cat tgc cca ctt 1920
Arg Pro Asn Leu Leu Pro Phe Leu Arg Asp Ser Thr His Cys Pro Leu
625 630 635 640
gaa aag gct ctt gag atc tgt caa cag aga aac ttt gta gaa gag aca 1968
Glu Lys Ala Leu Glu Ile Cys Gln Gln Arg Asn Phe Val Glu Glu Thr
645 650 655
gtt tat ctt ctg agc cga atg ggt aat agc cga agt gcc ctg aag atg 2016
Val Tyr Leu Leu Ser Arg Met Gly Asn Ser Arg Ser Ala Leu Lys Met
660 665 670
att atg gag gaa tta cat gat gtt gat aaa gca atc gaa ttt gcc aag 2064
Ile Met Glu Glu Leu His Asp Val Asp Lys Ala Ile Glu Phe Ala Lys
675 680 685
gag caa gat gat gga gag ctg tgg gaa gat ttg att tta tat tcc att 2112
Glu Gln Asp Asp Gly Glu Leu Trp Glu Asp Leu Ile Leu Tyr Ser Ile
690 695 700
gac aaa cca cca ttt att act ggc ttg tta aac aac att ggc aca cat 2160
Asp Lys Pro Pro Phe Ile Thr Gly Leu Leu Asn Asn Ile Gly Thr His
705 710 715 720
gtt gac cca att cta ctg att cac cgt att aag gaa gga atg gag atc 2208
Val Asp Pro Ile Leu Leu Ile His Arg Ile Lys Glu Gly Met Glu Ile
725 730 735
ccc aat ttg aga gat tcc ttg gtt aaa att ctg caa gac tac aat ttg 2256
Pro Asn Leu Arg Asp Ser Leu Val Lys Ile Leu Gln Asp Tyr Asn Leu
740 745 750
caa att ctg ctt cgt gaa ggc tgc aag aag att ctc gta gct gac tct 2304
Gln Ile Leu Leu Arg Glu Gly Cys Lys Lys Ile Leu Val Ala Asp Ser
755 760 765
ttg tcc tta ctg aag aaa atg cac cga act caa atg aaa ggt gtt ctt 2352
Leu Ser Leu Leu Lys Lys Met His Arg Thr Gln Met Lys Gly Val Leu
770 775 780
gtt gat gag gag aac atc tgt gag tcg tgc ctt tcc cct att ctt cca 2400
Val Asp Glu Glu Asn Ile Cys Glu Ser Cys Leu Ser Pro Ile Leu Pro
785 790 795 800
tca gat gca gct aag ccc ttc agc gtg gtg gtc ttc cat tgc cgg cac 2448
Ser Asp Ala Ala Lys Pro Phe Ser Val Val Val Phe His Cys Arg His
805 810 815
atg ttc cac aag gag tgc ctg ccc atg ccc agc atg aac tct gct gca 2496
Met Phe His Lys Glu Cys Leu Pro Met Pro Ser Met Asn Ser Ala Ala
820 825 830
cag ttc tgc aac atc tgc agt gct aag aac cgt gga cca gga agt gca 2544
Gln Phe Cys Asn Ile Cys Ser Ala Lys Asn Arg Gly Pro Gly Ser Ala
835 840 845
att ttg gag atg aaa aaa tag 2565
Ile Leu Glu Met Lys Lys
850
<210>60
<211>854
<212>PRT
<213>人
<400>60
Met Ala Glu Ala Glu Glu Gln Glu Thr Gly Ser Leu Glu Glu Ser Thr
1 5 10 15
Asp Glu Ser Glu Glu Glu Glu Ser Glu Glu Glu Pro Lys Leu Lys Tyr
20 25 30
Glu Arg Leu Ser Asn Gly Val Thr Glu Ile Leu Gln Lys Asp Ala Ala
35 40 45
Ser Cys Met Thr Val His Asp Lys Phe Leu Ala Leu Gly Thr His Tyr
50 55 60
Gly Lys Val Tyr Leu Leu Asp Val Gln Gly Asn Ile Thr Gln Lys Phe
65 70 75 80
Asp Val Ser Pro Val Lys Ile Asn Gln Ile Ser Leu Asp Glu Ser Gly
85 90 95
Glu His Met Gly Val Cys Ser Glu Asp Gly Lys Val Gln Val Phe Gly
100 105 110
Leu Tyr Ser Gly Glu Glu Phe His Glu Thr Phe Asp Cys Pro Ile Lys
115 120 125
Ile Ile Ala Val His Pro His Phe Val Arg Ser Ser Cys Lys Gln Phe
130 135 140
Val Thr Gly Gly Lys Lys Leu Leu Leu Phe Glu Arg Ser Trp Met Asn
145 150 155 160
Arg Trp Lys Ser Ala Val Leu His Glu Gly Glu Gly Asn Ile Arg Ser
165 170 175
Val Lys Trp Arg Gly His Leu Ile Ala Trp Ala Asn Asn Met Gly Val
180 185 190
Lys Ile Phe Asp Ile Ile Ser Lys Gln Arg Ile Thr Asn Val Pro Arg
195 200 205
Asp Asp Ile Ser Leu Arg Pro Asp Met Tyr Pro Cys Ser Leu Cys Trp
210 215 220
Lys Asp Asn Val Thr Leu Ile Ile Gly Trp Gly Thr Ser Val Lys Val
225 230 235 240
Cys Ser Val Lys Glu Arg His Ala Ser Glu Met Arg Asp Leu Pro Ser
245 250 255
Arg Tyr Val Glu Ile Val Ser Gln Phe Glu Thr Glu Phe Tyr Ile Ser
260 265 270
Gly Leu Ala Pro Leu Cys Asp Gln Leu Val Val Leu Ser Tyr Val Lys
275 280 285
Glu Ile Ser Glu Lys Thr Glu Arg Glu Tyr Cys Ala Arg Pro Arg Leu
290 295 300
Asp Ile Ile Gln Pro Leu Ser Glu Thr Cys Glu Glu Ile Ser Ser Asp
305 310 315 320
Ala Leu Thr Val Arg Gly Phe Gln Glu Asn Glu Cys Arg Asp Tyr His
325 330 335
Leu Glu Tyr Ser Glu Gly Glu Ser Leu Phe Tyr Ile Val Ser Pro Arg
340 345 350
Asp Val Val Val Ala Lys Glu Arg Asp Gln Asp Asp His Ile Asp Trp
355 360 365
Leu Leu Glu Lys Lys Lys Tyr Glu Glu Ala Leu Met Ala Ala Glu Ile
370 375 380
Ser Gln Lys Asn Ile Lys Arg His Lys Ile Leu Asp Ile Gly Leu Ala
385 390 395 400
Tyr Ile Asn His Leu Val Glu Arg Gly Asp Tyr Asp Ile Ala Ala Arg
405 410 415
Lys Cys Gln Lys Ile Leu Gly Lys Asn Ala Ala Leu Trp Glu Tyr Glu
420 425 430
Val Tyr Lys Phe Lys Glu Ile Gly Gln Leu Lys Ala Ile Ser Pro Tyr
435 440 445
Leu Pro Arg Gly Asp Pro Val Leu Lys Pro Leu Ile Tyr Glu Met Ile
450 455 460
Leu His Glu Phe Leu Glu Ser Asp Tyr Glu Gly Phe Ala Thr Leu Ile
465 470 475 480
Arg Glu Trp Pro Gly Asp Leu Tyr Asn Asn Ser Val Ile Val Gln Ala
485 490 495
Val Arg Asp His Leu Lys Lys Asp Ser Gln Asn Lys Thr Leu Leu Lys
500 505 510
Thr Leu Ala Glu Leu Tyr Thr Tyr Asp Lys Asn Tyr Gly Asn Ala Leu
515 520 525
Glu Ile Tyr Leu Thr Leu Arg His Lys Asp Val Phe Gln Leu Ile His
530 535 540
Lys His Asn Leu Phe Ser Ser Ile Lys Asp Lys Ile Val Leu Leu Met
545 550 555 560
Asp Phe Asp Ser Glu Lys Ala Val Asp Met Leu Leu Asp Asn Glu Asp
565 570 575
Lys Ile Ser Ile Lys Lys Val Val Glu Glu Leu Glu Asp Arg Pro Glu
580 585 590
Leu Gln His Val Tyr Leu His Lys Leu Phe Lys Arg Asp His His Lys
595 600 605
Gly Gln Arg Tyr His Glu Lys Gln Ile Ser Leu Tyr Ala Glu Tyr Asp
610 615 620
Arg Pro Asn Leu Leu Pro Phe Leu Arg Asp Ser Thr His Cys Pro Leu
625 630 635 640
Glu Lys Ala Leu Glu Ile Cys Gln Gln Arg Asn Phe Val Glu Glu Thr
645 650 655
Val Tyr Leu Leu Ser Arg Met Gly Asn Ser Arg Ser Ala Leu Lys Met
660 665 670
Ile Met Glu Glu Leu His Asp Val Asp Lys Ala Ile Glu Phe Ala Lys
675 680 685
Glu Gln Asp Asp Gly Glu Leu Trp Glu Asp Leu Ile Leu Tyr Ser Ile
690 695 700
Asp Lys Pro Pro Phe Ile Thr Gly Leu Leu Asn Asn Ile Gly Thr His
705 710 715 720
Val Asp Pro Ile Leu Leu Ile His Arg Ile Lys Glu Gly Met Glu Ile
725 730 735
Pro Asn Leu Arg Asp Ser Leu Val Lys Ile Leu Gln Asp Tyr Asn Leu
740 745 750
Gln Ile Leu Leu Arg Glu Gly Cys Lys Lys Ile Leu Val Ala Asp Ser
755 760 765
Leu Ser Leu Leu Lys Lys Met His Arg Thr Gln Met Lys Gly Val Leu
770 775 780
Val Asp Glu Glu Asn Ile Cys Glu Ser Cys Leu Ser Pro Ile Leu Pro
785 790 795 800
Ser Asp Ala Ala Lys Pro Phe Ser Val Val Val Phe His Cys Arg His
805 810 815
Met Phe His Lys Glu Cys Leu Pro Met Pro Ser Met Asn Ser Ala Ala
820 825 830
Gln Phe Cys Asn Ile Cys Ser Ala Lys Asn Arg Gly Pro Gly Ser Ala
835 840 845
Ile Leu Glu Met Lys Lys
850
<210>61
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<220>
<221>CDS
<222>(1)..(1305)
<400>61
atg tac tat aaa atc tct tat tta tta tct atc agt att cta tta ttt 48
Met Tyr Tyr Lys Ile Ser Tyr Leu Leu Ser Ile Ser Ile Leu Leu Phe
1 5 10 15
ttc gcg aaa tgt gaa aaa gta aaa aat aag gca gtg gag aag aaa gat 96
Phe Ala Lys Cys Glu Lys Val Lys Asn Lys Ala Val Glu Lys Lys Asp
20 25 30
gat cga aat gaa cga gaa ctg gca aag cac tta ctt gat gat tac tac 144
Asp Arg Asn Glu Arg Glu Leu Ala Lys His Leu Leu Asp Asp Tyr Tyr
35 40 45
caa tat act cga ccg gtt cgg aat tat tcc agt gtg ctc aat gtg acg 192
Gln Tyr Thr Arg Pro Val Arg Asn Tyr Ser Ser Val Leu Asn Val Thr
50 55 60
gta cag cca caa att tac aac ttg gta gag gtg aat gaa caa aat gag 240
Val Gln Pro Gln Ile Tyr Asn Leu Val Glu Val Asn Glu Gln Asn Glu
65 70 75 80
caa atc aaa ata ttg ctc tgg ttc ccc caa agt tgg aaa gac gat tat 288
Gln Ile Lys Ile Leu Leu Trp Phe Pro Gln Ser Trp Lys Asp Asp Tyr
85 90 95
cta aca tgg gat cct aag gaa tgg aac gga ata gag aga ata ata ata 336
Leu Thr Trp Asp Pro Lys Glu Trp Asn Gly Ile Glu Arg Ile Ile Ile
100 105 110
ccc aaa tcg caa att tgg att cca gat gga tat ata ttt aat aca gta 384
Pro Lys Ser Gln Ile Trp Ile Pro Asp Gly Tyr Ile Phe Asn Thr Val
115 120 125
gaa gaa act gaa ccg tta gaa aac cac aat gca aga gta aga tac gat 432
Glu Glu Thr Glu Pro Leu Glu Asn His Asn Ala Arg Val Arg Tyr Asp
130 135 140
ggg cga gtg gaa gtt gat ttc aat aaa ctc gtc gac ttg acg tgc cct 480
Gly Arg Val Glu Val Asp Phe Asn Lys Leu Val Asp Leu Thr Cys Pro
145 150 155 160
atg tca gtg ctc tct ttc cca ttt gat gtt caa tta tgt gcc ctc cag 528
Met Ser Val Leu Ser Phe Pro Phe Asp Val Gln Leu Cys Ala Leu Gln
165 170 175
ttt ggc tcc tgg tcg tat caa gct cat gcg att agc ttc aac gta ctc 576
Phe Gly Ser Trp Ser Tyr Gln Ala His Ala Ile Ser Phe Asn Val Leu
180 185 190
gac aca ttt gtc cca aag aaa agc aag aat tct gaa tgg gac att gta 624
Asp Thr Phe Val Pro Lys Lys Ser Lys Asn Ser Glu Trp Asp Ile Val
195 200 205
tcg ttt aat gct aca aag atg aca aca aaa tat ggt gac acg ctt gga 672
Ser Phe Asn Ala Thr Lys Met Thr Thr Lys Tyr Gly Asp Thr Leu Gly
210 215 220
gga ttc aat gtt tat gaa gag att ttc tat tac ttg gaa ctt cgc cga 720
Gly Phe Asn Val Tyr Glu Glu Ile Phe Tyr Tyr Leu Glu Leu Arg Arg
225 230 235 240
aag cca ttg tat tac att gta gtc att ctg ctc cca tca ttt tta att 768
Lys Pro Leu Tyr Tyr Ile Val Val Ile Leu Leu Pro Ser Phe Leu Ile
245 250 255
gtt acc gtc tca aac att gga ctg ttt acg cct cat gga gtt cac gga 816
Val Thr Val Ser Asn Ile Gly Leu Phe Thr Pro His Gly Val His Gly
260 265 270
gac aga gaa gag cat gtg tca ttg ggt ctc act aca atg ctt acc atg 864
Asp Arg Glu Glu His Val Ser Leu Gly Leu Thr Thr Met Leu Thr Met
275 280 285
gct gtt atc tta gac atg gtc aca gga caa atg cca aga agt agt gaa 912
Ala Val Ile Leu Asp Met Val Thr Gly Gln Met Pro Arg Ser Ser Glu
290 295 300
gga ata cca cta ttg gga atg tat gtg ctg att gaa ttt gtt ata tct 960
Gly Ile Pro Leu Leu Gly Met Tyr Val Leu Ile Glu Phe Val Ile Ser
305 310 315 320
gta att gct gta tta gta tca gtt gta ata att ttt gca cac gaa agg 1008
Val Ile Ala Val Leu Val Ser Val Val Ile Ile Phe Ala His Glu Arg
325 330 335
atg cta tat ctc gat gca act cct ccg tac tgg gtg tgc aaa ttg ttt 1056
Met Leu Tyr Leu Asp Ala Thr Pro Pro Tyr Trp Val Cys Lys Leu Phe
340 345 350
tca gat gac tgc aaa atg tca ttg gaa gaa ata gaa gaa gat ttt tgt 1104
Ser Asp Asp Cys Lys Met Ser Leu Glu Glu Ile Glu Glu Asp Phe Cys
355 360 365
tca aaa cca gct gat ctg gtg caa gag tta agg ttt tgt atg gag gaa 1152
Ser Lys Pro Ala Asp Leu Val Gln Glu Leu Arg Phe Cys Met Glu Glu
370 375 380
atc aaa cga tat ctt gac gaa cag gat tcg aca gag aag aac cga att 1200
Ile Lys Arg Tyr Leu Asp Glu Gln Asp Ser Thr Glu Lys Asn Arg Ile
385 390 395 400
ata tgg cag agg ttt ttc tcg tgg aca gat att ata ttc agt ata ttc 1248
Ile Trp Gln Arg Phe Phe Ser Trp Thr Asp Ile Ile Phe Ser Ile Phe
405 410 415
ttt ttt gtt gtt aat tgt ctt gtg aca ttt tac atg ttt atg gag ttt 1296
Phe Phe Val Val Asn Cys Leu Val Thr Phe Tyr Met Phe Met Glu Phe
420 425 430
atg ttt tga 1305
Met Phe
<210>62
<211>434
<212>PRT
<213>线虫
<400>62
Met Tyr Tyr Lys Ile Ser Tyr Leu Leu Ser Ile Ser Ile Leu Leu Phe
1 5 10 15
Phe Ala Lys Cys Glu Lys Val Lys Asn Lys Ala Val Glu Lys Lys Asp
20 25 30
Asp Arg Asn Glu Arg Glu Leu Ala Lys His Leu Leu Asp Asp Tyr Tyr
35 40 45
Gln Tyr Thr Arg Pro Val Arg Asn Tyr Ser Ser Val Leu Asn Val Thr
50 55 60
Val Gln Pro Gln Ile Tyr Asn Leu Val Glu Val Asn Glu Gln Asn Glu
65 70 75 80
Gln Ile Lys Ile Leu Leu Trp Phe Pro Gln Ser Trp Lys Asp Asp Tyr
85 90 95
Leu Thr Trp Asp Pro Lys Glu Trp Asn Gly Ile Glu Arg Ile Ile Ile
100 105 110
Pro Lys Ser Gln Ile Trp Ile Pro Asp Gly Tyr Ile Phe Asn Thr Val
115 120 125
Glu Glu Thr Glu Pro Leu Glu Asn His Asn Ala Arg Val Arg Tyr Asp
130 135 140
Gly Arg Val Glu Val Asp Phe Asn Lys Leu Val Asp Leu Thr Cys Pro
145 150 155 160
Met Ser Val Leu Ser Phe Pro Phe Asp Val Gln Leu Cys Ala Leu Gln
165 170 175
Phe Gly Ser Trp Ser Tyr Gln Ala His Ala Ile Ser Phe Asn Val Leu
180 185 190
Asp Thr Phe Val Pro Lys Lys Ser Lys Asn Ser Glu Trp Asp Ile Val
195 200 205
Ser Phe Asn Ala Thr Lys Met Thr Thr Lys Tyr Gly Asp Thr Leu Gly
210 215 220
Gly Phe Asn Val Tyr Glu Glu Ile Phe Tyr Tyr Leu Glu Leu Arg Arg
225 230 235 240
Lys Pro Leu Tyr Tyr Ile Val Val Ile Leu Leu Pro Ser Phe Leu Ile
245 250 255
Val Thr Val Ser Asn Ile Gly Leu Phe Thr Pro His Gly Val His Gly
260 265 270
Asp Arg Glu Glu His Val Ser Leu Gly Leu Thr Thr Met Leu Thr Met
275 280 285
Ala Val Ile Leu Asp Met Val Thr Gly Gln Met Pro Arg Ser Ser Glu
290 295 300
Gly Ile Pro Leu Leu Gly Met Tyr Val Leu Ile Glu Phe Val Ile Ser
305 310 315 320
Val Ile Ala Val Leu Val Ser Val Val Ile Ile Phe Ala His Glu Arg
325 330 335
Met Leu Tyr Leu Asp Ala Thr Pro Pro Tyr Trp Val Cys Lys Leu Phe
340 345 350
Ser Asp Asp Cys Lys Met Ser Leu Glu Glu Ile Glu Glu Asp Phe Cys
355 360 365
Ser Lys Pro Ala Asp Leu Val Gln Glu Leu Arg Phe Cys Met Glu Glu
370 375 380
Ile Lys Arg Tyr Leu Asp Glu Gln Asp Ser Thr Glu Lys Asn Arg Ile
385 390 395 400
Ile Trp Gln Arg Phe Phe Ser Trp Thr Asp Ile Ile Phe Ser Ile Phe
405 410 415
Phe Phe Val Val Asn Cys Leu Val Thr Phe Tyr Met Phe Met Glu Phe
420 425 430
Met Phe
<210>63
<211>1440
<212>DNA
<213>人
<220>
<221>CDS
<222>(1)..(1440)
<400>63
atg aac tgg tcc cat tcc tgc atc tcc ttt tgc tgg atc tac ttt gct 48
Met Asn Trp Ser His Ser Cys Ile Ser Phe Cys Trp Ile Tyr Phe Ala
1 5 10 15
gct tcc aga ctg aga gct gca gag acg gca gat gga aaa tat gct cag 96
Ala Ser Arg Leu Arg Ala Ala Glu Thr Ala Asp Gly Lys Tyr Ala Gln
20 25 30
aag ttg ttt aat gac ctt ttt gaa gat tat tct aat gct ctt cgt cca 144
Lys Leu Phe Asn Asp Leu Phe Glu Asp Tyr Ser Asn Ala Leu Arg Pro
35 40 45
gtg gaa gat aca gat aaa gtc ctg aat gtg acc ctg cag att acg ctc 192
Val Glu Asp Thr Asp Lys Val Leu Asn Val Thr Leu Gln Ile Thr Leu
50 55 60
tct cag att aag gat atg gat gaa aga aac caa att ctg act gct tat 240
Ser Gln Ile Lys Asp Met Asp Glu Arg Asn Gln Ile Leu Thr Ala Tyr
65 70 75 80
ttg tgg atc cgc caa atc tgg cac gat gcc tat ctc acg tgg gac cga 288
Leu Trp Ile Arg Gln Ile Trp His Asp Ala Tyr Leu Thr Trp Asp Arg
85 90 95
gat cag tac gat ggc cta gac tcc atc agg atc ccc agt gac ctc gtg 336
Asp Gln Tyr Asp Gly Leu Asp Ser Ile Arg Ile Pro Ser Asp Leu Val
100 105 110
tgg agg cca gac atc gtc tta tat aac aag gct gat gat gaa tct tca 384
Trp Arg Pro Asp Ile Val Leu Tyr Asn Lys Ala Asp Asp Glu Ser Ser
115 120 125
gag cct gtg aac acc aat gtg gtc ctg cgg tat gat ggg ctg atc acc 432
Glu Pro Val Asn Thr Asn Val Val Leu Arg Tyr Asp Gly Leu Ile Thr
130 135 140
tgg gat gca ccg gcc atc acc aaa agc tcc tgt gtg gtg gat gtc acc 480
Trp Asp Ala Pro Ala Ile Thr Lys Ser Ser Cys Val Val Asp Val Thr
145 150 155 160
tac ttc cct ttt gac aac cag cag tgc aac ctg act ttt ggt tcc tgg 528
Tyr Phe Pro Phe Asp Asn Gln Gln Cys Asn Leu Thr Phe Gly Ser Trp
165 170 175
acc tac aat ggc aat cag gtg gac ata ttc aac gcc ttg gac agc gga 576
Thr Tyr Asn Gly Asn Gln Val Asp Ile Phe Asn Ala Leu Asp Ser Gly
180 185 190
gat ctc tct gac ttc att gaa gat gtg gaa tgg gag gtc cat ggc atg 624
Asp Leu Ser Asp Phe Ile Glu Asp Val Glu Trp Glu Val His Gly Met
195 200 205
ccc gct gtg aag aat gtg atc tcc tat ggc tgc tgc tct gag cct tac 672
Pro Ala Val Lys Asn Val Ile Ser Tyr Gly Cys Cys Ser Glu Pro Tyr
210 215 220
ccg gat gtc aca ttc acc ctc ctt ctg aag agg agg tcc tcg ttc tat 720
Pro Asp Val Thr Phe Thr Leu Leu Leu Lys Arg Arg Ser Ser Phe Tyr
225 230 235 240
atc gtc aac ctc ctc atc cca tgc gtc ctc ata tct ttt ctg gct cct 768
Ile Val Asn Leu Leu Ile Pro Cys Val Leu Ile Ser Phe Leu Ala Pro
245 250 255
ctg agt ttt tat ctc cca gca gcc tcc gga gaa aag gtc tcc ctg gga 816
Leu Ser Phe Tyr Leu Pro Ala Ala Ser Gly Glu Lys Val Ser Leu Gly
260 265 270
gtg acc atc ctg ttg gcc atg act gta ttt cag cta atg gtg gca gaa 864
Val Thr Ile Leu Leu Ala Met Thr Val Phe Gln Leu Met Val Ala Glu
275 280 285
atc atg ccg gcc tca gaa aat gtg ccc ctg ata ggt aaa tac tac ata 912
Ile Met Pro Ala Ser Glu Asn Val Pro Leu Ile Gly Lys Tyr Tyr Ile
290 295 300
gcc acg atg gcc ctg atc aca gcc tcc act gcg ttg acc atc atg gtg 960
Ala Thr Met Ala Leu Ile Thr Ala Ser Thr Ala Leu Thr Ile Met Val
305 310 315 320
atg aat atc cac ttc tgt ggg gcc gag gcc cgg ccg gtg cca cac tgg 1008
Met Asn Ile His Phe Cys Gly Ala Glu Ala Arg Pro Val Pro His Trp
325 330 335
gcc agg gtg gtc atc ctg aaa tac atg tcc agg gtc ttg ttt gtc tat 1056
Ala Arg Val Val Ile Leu Lys Tyr Met Ser Arg Val Leu Phe Val Tyr
340 345 350
gat gtg ggt gaa agc tgc ctc agc ccg cac cac agt aga gag cgg gac 1104
Asp Val Gly Glu Ser Cys Leu Ser Pro His His Ser Arg Glu Arg Asp
355 360 365
cac ctc acg aaa gtt tat agc aaa ctc cca gag tct aac ctg aaa gca 1152
His Leu Thr Lys Val Tyr Ser Lys Leu Pro Glu Ser Asn Leu Lys Ala
370 375 380
gcc agg aac aaa gac ctt tcc aga aag aag gac atg aac aaa cgc tta 1200
Ala Arg Asn Lys Asp Leu Ser Arg Lys Lys Asp Met Asn Lys Arg Leu
385 390 395 400
aag aac gac ctg ggc tgc cag ggt aag aac cct cag gag gcc gag agt 1248
Lys Asn Asp Leu Gly Cys Gln Gly Lys Asn Pro Gln Glu Ala Glu Ser
405 410 415
tac tgt gca cag tac aaa gtg ctg acg agg aat att gag tac atc gcc 1296
Tyr Cys Ala Gln Tyr Lys Val Leu Thr Arg Asn Ile Glu Tyr Ile Ala
420 425 430
aag tgc ctc aaa gac cac aag gcc acc aat tcc aag ggg agt gaa tgg 1344
Lys Cys Leu Lys Asp His Lys Ala Thr Asn Ser Lys Gly Ser Glu Trp
435 440 445
aag aag gtg gcg aaa gtc ata gac cga ttc ttc atg tgg att ttt ttc 1392
Lys Lys Val Ala Lys Val Ile Asp Arg Phe Phe Met Trp Ile Phe Phe
450 455 460
att atg gtg ttt gtg atg act att ttg atc ata gca aga gcg gat tag 1440
Ile Met Val Phe Val Met Thr Ile Leu Ile Ile Ala Arg Ala Asp
465 470 475
<210>64
<211>479
<212>PRT
<213>人
<400>64
Met Asn Trp Ser His Ser Cys Ile Ser Phe Cys Trp Ile Tyr Phe Ala
1 5 10 15
Ala Ser Arg Leu Arg Ala Ala Glu Thr Ala Asp Gly Lys Tyr Ala Gln
20 25 30
Lys Leu Phe Asn Asp Leu Phe Glu Asp Tyr Ser Asn Ala Leu Arg Pro
35 40 45
Val Glu Asp Thr Asp Lys Val Leu Asn Val Thr Leu Gln Ile Thr Leu
50 55 60
Ser Gln Ile Lys Asp Met Asp Glu Arg Asn Gln Ile Leu Thr Ala Tyr
65 70 75 80
Leu Trp Ile Arg Gln Ile Trp His Asp Ala Tyr Leu Thr Trp Asp Arg
85 90 95
Asp Gln Tyr Asp Gly Leu Asp Ser Ile Arg Ile Pro Ser Asp Leu Val
100 105 110
Trp Arg Pro Asp Ile Val Leu Tyr Asn Lys Ala Asp Asp Glu Ser Ser
115 120 125
Glu Pro Val Asn Thr Asn Val Val Leu Arg Tyr Asp Gly Leu Ile Thr
130 135 140
Trp Asp Ala Pro Ala Ile Thr Lys Ser Ser Cys Val Val Asp Val Thr
145 150 155 160
Tyr Phe Pro Phe Asp Asn Gln Gln Cys Asn Leu Thr Phe Gly Ser Trp
165 170 175
Thr Tyr Asn Gly Asn Gln Val Asp Ile Phe Asn Ala Leu Asp Ser Gly
180 185 190
Asp Leu Ser Asp Phe Ile Glu Asp Val Glu Trp Glu Val His Gly Met
195 200 205
Pro Ala Val Lys Asn Val Ile Ser Tyr Gly Cys Cys Ser Glu Pro Tyr
210 215 220
Pro Asp Val Thr Phe Thr Leu Leu Leu Lys Arg Arg Ser Ser Phe Tyr
225 230 235 240
Ile Val Asn Leu Leu Ile Pro Cys Val Leu Ile Ser Phe Leu Ala Pro
245 250 255
Leu Ser Phe Tyr Leu Pro Ala Ala Ser Gly Glu Lys Val Ser Leu Gly
260 265 270
Val Thr Ile Leu Leu Ala Met Thr Val Phe Gln Leu Met Val Ala Glu
275 280 285
Ile Met Pro Ala Ser Glu Asn Val Pro Leu Ile Gly Lys Tyr Tyr Ile
290 295 300
Ala Thr Met Ala Leu Ile Thr Ala Ser Thr Ala Leu Thr Ile Met Val
305 310 315 320
Met Asn Ile His Phe Cys Gly Ala Glu Ala Arg Pro Val Pro His Trp
325 330 335
Ala Arg Val Val Ile Leu Lys Tyr Met Ser Arg Val Leu Phe Val Tyr
340 345 350
Asp Val Gly Glu Ser Cys Leu Ser Pro His His Ser Arg Glu Arg Asp
355 360 365
His Leu Thr Lys Val Tyr Ser Lys Leu Pro Glu Ser Asn Leu Lys Ala
370 375 380
Ala Arg Asn Lys Asp Leu Ser Arg Lys Lys Asp Met Asn Lys Arg Leu
385 390 395 400
Lys Asn Asp Leu Gly Cys Gln Gly Lys Asn Pro Gln Glu Ala Glu Ser
405 410 415
Tyr Cys Ala Gln Tyr Lys Val Leu Thr Arg Asn Ile Glu Tyr Ile Ala
420 425 430
Lys Cys Leu Lys Asp His Lys Ala Thr Asn Ser Lys Gly Ser Glu Trp
435 440 445
Lys Lys Val Ala Lys Val Ile Asp Arg Phe Phe Met Trp Ile Phe Phe
450 455 460
Ile Met Val Phe Val Met Thr Ile Leu Ile Ile Ala Arg Ala Asp
465 470 475
<210>65
<211>1674
<212>DNA
<213>线虫
<220>
<221>CDS
<222>(1)..(1674)
<400>65
atg gca tcg tct aat aac gat ggt ccc att gag cct gag gct gaa ccg 48
Met Ala Ser Ser Asn Asn Asp Gly Pro Ile Glu Pro Glu Ala Glu Pro
1 5 10 15
tgg cga ata aca caa aac gat cat ctc gag caa gat ctt ttg gaa gaa 96
Trp Arg Ile Thr Gln Asn Asp His Leu Glu Gln Asp Leu Leu Glu Glu
20 25 30
gat gca gag agt cag gag aga gtt gat att cca gtt gat gat gtg gaa 144
Asp Ala Glu Ser Gln Glu Arg Val Asp Ile Pro Val Asp Asp Val Glu
35 40 45
aaa gcg ttc tcc ttc aaa aaa tta tgg gcg ttc aca ggg ccc gga ttt 192
Lys Ala Phe Ser Phe Lys Lys Leu Trp Ala Phe Thr Gly Pro Gly Phe
50 55 60
ctc atg agt att gcc tat ttg gac cca gga aac att gaa agc gac ctt 240
Leu Met Ser Ile Ala Tyr Leu Asp Pro Gly Asn Ile Glu Ser Asp Leu
65 70 75 80
cag tct ggc gca caa gcg gct tac aaa ctt ttg tgg gtt ttg ctc tca 288
Gln Ser Gly Ala Gln Ala Ala Tyr Lys Leu Leu Trp Val Leu Leu Ser
85 90 95
gct cat att atc gga atg ttg ctc caa cga atg tct gca aga ctt gga 336
Ala His Ile Ile Gly Met Leu Leu Gln Arg Met Ser Ala Arg Leu Gly
100 105 110
gtt gtc agt gga aaa cat atg gca gag gtt gcc tac caa ttt tac cca 384
Val Val Ser Gly Lys His Met Ala Glu Val Ala Tyr Gln Phe Tyr Pro
115 120 125
aga ctt cct cgc atc att ctc tgg ctt atg atc gag att gca att gtg 432
Arg Leu Pro Arg Ile Ile Leu Trp Leu Met Ile Glu Ile Ala Ile Val
130 135 140
tgt agt gat atg caa gaa gtt att gga aca gca att gcc att ttc ttg 480
Cys Ser Asp Met Gln Glu Val Ile Gly Thr Ala Ile Ala Ile Phe Leu
145 150 155 160
ctc tct aaa gga ttc gtt cca ctc tac gtt gga gtt ttc atc aca att 528
Leu Ser Lys Gly Phe Val Pro Leu Tyr Val Gly Val Phe Ile Thr Ile
165 170 175
ctt gac acc ttc aca ttt ttg ctg atc gac cgg tac gga atc cga aaa 576
Leu Asp Thr Phe Thr Phe Leu Leu Ile Asp Arg Tyr Gly Ile Arg Lys
180 185 190
ctg gaa tta atc ttt gga ttt ctt att tta aca atg aca gtg tca ttt 624
Leu Glu Leu Ile Phe Gly Phe Leu Ile Leu Thr Met Thr Val Ser Phe
195 200 205
ggc tat gag ttt gtc gtt gtg aaa cct cca att ggt gaa gtt ata tct 672
Gly Tyr Glu Phe Val Val Val Lys Pro Pro Ile Gly Glu Val Ile Ser
210 215 220
gga atg gtg gta cct tgg tgc gct gga tgt gga aaa gga gag ttt atg 720
Gly Met Val Val Pro Trp Cys Ala Gly Cys Gly Lys Gly Glu Phe Met
225 230 235 240
caa gcg ata tca gtt gtc gga gct gtc atc atg ccg cac aat ttg tac 768
Gln Ala Ile Ser Val Val Gly Ala Val Ile Met Pro His Asn Leu Tyr
245 250 255
ctt cat tcg gct cta gtg aag tct cgc cgt gta gat cgt aaa gac cgt 816
Leu His Ser Ala Leu Val Lys Ser Arg Arg Val Asp Arg Lys Asp Arg
260 265 270
cgt cgt gtg gct gag gcc aac aaa tat ttc aca ctt gag tcg gca att 864
Arg Arg Val Ala Glu Ala Asn Lys Tyr Phe Thr Leu Glu Ser Ala Ile
275 280 285
gct ctt ttc ctc agc ttc ttc atc aac ctt ttt gtg gtc gcc gtt ttc 912
Ala Leu Phe Leu Ser Phe Phe Ile Asn Leu Phe Val Val Ala Val Phe
290 295 300
gca cat gga ctt tac cag aaa aca aat gcg gat gtt aga gaa atg tgc 960
Ala His Gly Leu Tyr Gln Lys Thr Asn Ala Asp Val Arg Glu Met Cys
305 310 315 320
ata gcc aga cac gac atc ccg gat gca gat ata ttc cca aat aac act 1008
Ile Ala Arg His Asp Ile Pro Asp Ala Asp Ile Phe Pro Asn Asn Thr
325 330 335
gaa cca gtt gag ggt gga att tat ctc gga tgc cag ttt gga gct att 1056
Glu Pro Val Glu Gly Gly Ile Tyr Leu Gly Cys Gln Phe Gly Ala Ile
340 345 350
gca atg ttt atc tgg gga att gga ata ttc gca gct gga cag tca tca 1104
Ala Met Phe Ile Trp Gly Ile Gly Ile Phe Ala Ala Gly Gln Ser Ser
355 360 365
aca atg aca gga aca tat aca gga cag ttt gtg atg gaa gga ttt gtg 1152
Thr Met Thr Gly Thr Tyr Thr Gly Gln Phe Val Met Glu Gly Phe Val
370 375 380
aaa att gag tgg ccc aaa tgg aag aga gtt cta att aca aga gcg att 1200
Lys Ile Glu Trp Pro Lys Trp Lys Arg Val Leu Ile Thr Arg Ala Ile
385 390 395 400
gca atc act cca acc ctc gtg ctc acg ttt tat tcg caa gga gtt caa 1248
Ala Ile Thr Pro Thr Leu Val Leu Thr Phe Tyr Ser Gln Gly Val Gln
405 410 415
aac tta aca gga atg aat gat ttc tta aat tgt gtt caa atg att caa 1296
Asn Leu Thr Gly Met Asn Asp Phe Leu Asn Cys Val Gln Met Ile Gln
420 425 430
ctt ccg ttt gca cta att cca atc atc aca ttt acc tcg agc cga aaa 1344
Leu Pro Phe Ala Leu Ile Pro Ile Ile Thr Phe Thr Ser Ser Arg Lys
435 440 445
ata atg cac gac ttc aga agc tct aaa gtt ttt caa att ttt gct ctg 1392
Ile Met His Asp Phe Arg Ser Ser Lys Val Phe Gln Ile Phe Ala Leu
450 455 460
atc act tct gcg tta att tta tcg att aac gtt tat ttt att tct gac 1440
Ile Thr Ser Ala Leu Ile Leu Ser Ile Asn Val Tyr Phe Ile Ser Asp
465 470 475 480
tac gtg ttt tct cga ctt ggt agt gag tgg tat atc ata atg gtt ctt 1488
Tyr Val Phe Ser Arg Leu Gly Ser Glu Trp Tyr Ile Ile Met Val Leu
485 490 495
gct ccg atc acc ttt gca tac gtg ctc ttt gtg tta tat cta gca cta 1536
Ala Pro Ile Thr Phe Ala Tyr Val Leu Phe Val Leu Tyr Leu Ala Leu
500 505 510
tac tgt ttg gtc tct tgt gaa att atc cca gac acc gtt tcc atc cga 1584
Tyr Cys Leu Val Ser Cys Glu Ile Ile Pro Asp Thr Val Ser Ile Arg
515 520 525
gga ttc agc ttt aac aag tca tac gaa aac gat gct ccg tgg ttg gcg 1632
Gly Phe Ser Phe Asn Lys Ser Tyr Glu Asn Asp Ala Pro Trp Leu Ala
530 535 540
gtt gat tca tca gca gtc cat gac aat gca gga tat caa taa 1674
Val Asp Ser Ser Ala Val His Asp Asn Ala Gly Tyr Gln
545 550 555
<210>66
<211>557
<212>PRT
<213>线虫
<400>66
Met Ala Ser Ser Asn Asn Asp Gly Pro Ile Glu Pro Glu Ala Glu Pro
1 5 10 15
Trp Arg Ile Thr Gln Asn Asp His Leu Glu Gln Asp Leu Leu Glu Glu
20 25 30
Asp Ala Glu Ser Gln Glu Arg Val Asp Ile Pro Val Asp Asp Val Glu
35 40 45
Lys Ala Phe Ser Phe Lys Lys Leu Trp Ala Phe Thr Gly Pro Gly Phe
50 55 60
Leu Met Ser Ile Ala Tyr Leu Asp Pro Gly Asn Ile Glu Ser Asp Leu
65 70 75 80
Gln Ser Gly Ala Gln Ala Ala Tyr Lys Leu Leu Trp Val Leu Leu Ser
85 90 95
Ala His Ile Ile Gly Met Leu Leu Gln Arg Met Ser Ala Arg Leu Gly
100 105 110
Val Val Ser Gly Lys His Met Ala Glu Val Ala Tyr Gln Phe Tyr Pro
115 120 125
Arg Leu Pro Arg Ile Ile Leu Trp Leu Met Ile Glu Ile Ala Ile Val
130 135 140
Cys Ser Asp Met Gln Glu Val Ile Gly Thr Ala Ile Ala Ile Phe Leu
145 150 155 160
Leu Ser Lys Gly Phe Val Pro Leu Tyr Val Gly Val Phe Ile Thr Ile
165 170 175
Leu Asp Thr Phe Thr Phe Leu Leu Ile Asp Arg Tyr Gly Ile Arg Lys
180 185 190
Leu Glu Leu Ile Phe Gly Phe Leu Ile Leu Thr Met Thr Val Ser Phe
195 200 205
Gly Tyr Glu Phe Val Val Val Lys Pro Pro Ile Gly Glu Val Ile Ser
210 215 220
Gly Met Val Val Pro Trp Cys Ala Gly Cys Gly Lys Gly Glu Phe Met
225 230 235 240
Gln Ala Ile Ser Val Val Gly Ala Val Ile Met Pro His Asn Leu Tyr
245 250 255
Leu His Ser Ala Leu Val Lys Ser Arg Arg Val Asp Arg Lys Asp Arg
260 265 270
Arg Arg Val Ala Glu Ala Asn Lys Tyr Phe Thr Leu Glu Ser Ala Ile
275 280 285
Ala Leu Phe Leu Ser Phe Phe Ile Asn Leu Phe Val Val Ala Val Phe
290 295 300
Ala His Gly Leu Tyr Gln Lys Thr Asn Ala Asp Val Arg Glu Met Cys
305 310 315 320
Ile Ala Arg His Asp Ile Pro Asp Ala Asp Ile Phe Pro Asn Asn Thr
325 330 335
Glu Pro Val Glu Gly Gly Ile Tyr Leu Gly Cys Gln Phe Gly Ala Ile
340 345 350
Ala Met Phe Ile Trp Gly Ile Gly Ile Phe Ala Ala Gly Gln Ser Ser
355 360 365
Thr Met Thr Gly Thr Tyr Thr Gly Gln Phe Val Met Glu Gly Phe Val
370 375 380
Lys Ile Glu Trp Pro Lys Trp Lys Arg Val Leu Ile Thr Arg Ala Ile
385 390 395 400
Ala Ile Thr Pro Thr Leu Val Leu Thr Phe Tyr Ser Gln Gly Val Gln
405 410 415
Asn Leu Thr Gly Met Asn Asp Phe Leu Asn Cys Val Gln Met Ile Gln
420 425 430
Leu Pro Phe Ala Leu Ile Pro Ile Ile Thr Phe Thr Ser Ser Arg Lys
435 440 445
Ile Met His Asp Phe Arg Ser Ser Lys Val Phe Gln Ile Phe Ala Leu
450 455 460
Ile Thr Ser Ala Leu Ile Leu Ser Ile Asn Val Tyr Phe Ile Ser Asp
465 470 475 480
Tyr Val Phe Ser Arg Leu Gly Ser Glu Trp Tyr Ile Ile Met Val Leu
485 490 495
Ala Pro Ile Thr Phe Ala Tyr Val Leu Phe Val Leu Tyr Leu Ala Leu
500 505 510
Tyr Cys Leu Val Ser Cys Glu Ile Ile Pro Asp Thr Val Ser Ile Arg
515 520 525
Gly Phe Ser Phe Asn Lys Ser Tyr Glu Asn Asp Ala Pro Trp Leu Ala
530 535 540
Val Asp Ser Ser Ala Val His Asp Asn Ala Gly Tyr Gln
545 550 555
<210>67
<211>1707
<212>DNA
<213>人
<220>
<221>CDS
<222>(1)..(1707)
<400>67
atg gtg ctg ggt cct gaa cag aag atg tca gat gac agt gtt tct gga 48
Met Val Leu Gly Pro Glu Gln Lys Met Ser Asp Asp Ser Val Ser Gly
1 5 10 15
gat cat ggg gag tct gcc agt ctt ggt aac atc aac cct gcc tat agt 96
Asp His Gly Glu Ser Ala Ser Leu Gly Asn lle Asn Pro Ala Tyr Ser
20 25 30
aat ccc tct ctt tca cag tcc cct ggg gac tca gag gag tac ttc gcc 144
Asn Pro Ser Leu Ser Gln Ser Pro Gly Asp Ser Glu Glu Tyr Phe Ala
35 40 45
act tac ttt aat gag aag atc tcc att cct gag gag gag tac tct tgt 192
Thr Tyr Phe Asn Glu Lys Ile Ser Ile Pro Glu Glu Glu Tyr Ser Cys
50 55 60
ttt agc ttt cgt aaa ctc tgg gct ttc acc gga cca ggt ttt ctt atg 240
Phe Ser Phe Arg Lys Leu Trp Ala Phe Thr Gly Pro Gly Phe Leu Met
65 70 75 80
agc att gcc tac ctg gat cca gga aat att gaa tcc gat ttg cag tct 288
Ser Ile Ala Tyr Leu Asp Pro Gly Asn Ile Glu Ser Asp Leu Gln Ser
85 90 95
gga gca gtg gct gga ttt aag ttg ctc tgg atc ctt ctg ttg gcc acc 336
Gly Ala Val Ala Gly Phe Lys Leu Leu Trp Ile Leu Leu Leu Ala Thr
100 105 110
ctt gtg ggg ctg ctg ctc cag cgg ctt gca gct aga ctg gga gtg gtt 384
Leu Val Gly Leu Leu Leu Gln Arg Leu Ala Ala Arg Leu Gly Val Val
115 120 125
act ggg ctg cat ctt gct gaa gta tgt cac cgt cag tat ccc aag gtc 432
Thr Gly Leu His Leu Ala Glu Val Cys His Arg Gln Tyr Pro Lys Val
130 135 140
cca cga gtc atc ctg tgg ctg atg gtg gag ttg gct atc atc ggc tca 480
Pro Arg Val Ile Leu Trp Leu Met Val Glu Leu Ala Ile Ile Gly Ser
145 150 155 160
gac atg caa gaa gtc att ggc tca gcc att gct atc aat ctt ctg tct 528
Asp Met Gln Glu Val Ile Gly Ser Ala Ile Ala Ile Asn Leu Leu Ser
165 170 175
gta gga aga att cct ctg tgg ggt ggc gtt ctc atc acc att gca gat 576
Val Gly Arg Ile Pro Leu Trp Gly Gly Val Leu Ile Thr Ile Ala Asp
180 185 190
act ttt gta ttt ctc ttc ttg gac aaa tat ggc ttg cgg aag cta gaa 624
Thr Phe Val Phe Leu Phe Leu Asp Lys Tyr Gly Leu Arg Lys Leu Glu
195 200 205
gca ttt ttt ggc ttt ctc atc act att atg gcc ctc aca ttt gga tat 672
Ala Phe Phe Gly Phe Leu Ile Thr Ile Met Ala Leu Thr Phe Gly Tyr
210 215 220
gag tat gtt aca gtg aaa ccc agc cag agc cag gta ctc aag ggc atg 720
Glu Tyr Val Thr Val Lys Pro Ser Gln Ser Gln Val Leu Lys Gly Met
225 230 235 240
ttc gta cca tcc tgt tca ggc tgt cgc act cca cag att gaa cag gct 768
Phe Val Pro Ser Cys Ser Gly Cys Arg Thr Pro Gln Ile Glu Gln Ala
245 250 255
gtg ggc atc gtg gga gct gtc atc atg cca cac aac atg tac ctg cat 816
Val Gly Ile Val Gly Ala Val Ile Met Pro His Asn Met Tyr Leu His
260 265 270
tct gcc tta gtc aag tct aga cag gta aac cgg aac aat aag cag gaa 864
Ser Ala Leu Val Lys Ser Arg Gln Val Asn Arg Asn Asn Lys Gln Glu
275 280 285
gtt cga gaa gcc aat aag tac ttt ttc att gaa tcc tgc att gca ctc 912
Val Arg Glu Ala Asn Lys Tyr Phe Phe Ile Glu Ser Cys Ile Ala Leu
290 295 300
ttt gtt tcc ttc atc atc aat gtc ttt gtt gtc tca gtc ttt gct gaa 960
Phe Val Ser Phe Ile Ile Asn Val Phe Val Val Ser Val Phe Ala Glu
305 310 315 320
gca ttt ttt ggg aaa acc aac gag cag gtg gtt gaa gtc tgt aca aat 1008
Ala Phe Phe Gly Lys Thr Asn Glu Gln Val Val Glu Val Cys Thr Asn
325 330 335
acc agc agt cct cat gct ggc ctc ttt cct aaa gat aac tcg aca ctg 1056
Thr Ser Ser Pro His Ala Gly Leu Phe Pro Lys Asp Asn Ser Thr Leu
340 345 350
gct gtg gac atc tac aaa ggg ggt gtt gtg ctg gga tgt tac ttt ggg 1104
Ala Val Asp Ile Tyr Lys Gly Gly Val Val Leu Gly Cys Tyr Phe Gly
355 360 365
cct gct gca ctc tac att tgg gca gtg ggg atc ctg gct gca gga cag 1152
Pro Ala Ala Leu Tyr Ile Trp Ala Val Gly Ile Leu Ala Ala Gly Gln
370 375 380
agc tcc acc atg aca gga acc tat tct ggc cag ttt gtc atg gag gga 1200
Ser Ser Thr Met Thr Gly Thr Tyr Ser Gly Gln Phe Val Met Glu Gly
385 390 395 400
ttc ctg aac cta aag tgg tca cgc ttt gcc cga gtg gtt ctg act cgc 1248
Phe Leu Asn Leu Lys Trp Ser Arg Phe Ala Arg Val Val Leu Thr Arg
405 410 415
tct att gcc atc atc ccc act ctg ctt gtt gct gtc ttc caa gat gta 1296
Ser Ile Ala Ile Ile Pro Thr Leu Leu Val Ala Val Phe Gln Asp Val
420 425 430
gag cat cta aca ggg atg aat gac ttt ctg aat gtt cta cag agc tta 1344
Glu His Leu Thr Gly Met Asn Asp Phe Leu Asn Val Leu Gln Ser Leu
435 440 445
cag ctt ccc ttt gct ctc ata ccc atc ctc aca ttt acg agc ttg cgg 1392
Gln Leu Pro Phe Ala Leu Ile Pro Ile Leu Thr Phe Thr Ser Leu Arg
450 455 460
cca gta atg agt gac ttt gcc aat gga cta ggc tgg cgg att gca gga 1440
Pro Val Met Ser Asp Phe Ala Asn Gly Leu Gly Trp Arg Ile Ala Gly
465 470 475 480
gga atc ttg gtc ctt atc atc tgt tcc atc aat atg tac ttt gta gtg 1488
Gly Ile Leu Val Leu Ile Ile Cys Ser Ile Asn Met Tyr Phe Val Val
485 490 495
gtt tat gtc cgg gac cta ggg cat gtg gca tta tat gtg gtg gct gct 1536
Val Tyr Val Arg Asp Leu Gly His Val Ala Leu Tyr Val Val Ala Ala
500 505 510
gtg gtc agc gtg gct tat ctg ggc ttt gtg ttc tac ttg ggt tgg caa 1584
Val Val Ser Val Ala Tyr Leu Gly Phe Val Phe Tyr Leu Gly Trp Gln
515 520 525
tgt ttg att gca ctg ggc atg tcc ttc ctg gac tgt ggg cat acg tgc 1632
Cys Leu Ile Ala Leu Gly Met Ser Phe Leu Asp Cys Gly His Thr Cys
530 535 540
cat ctg gga ttg aca gct cag cct gaa ctc tat ctt ctg aac acc atg 1680
His Leu Gly Leu Thr Ala Gln Pro Glu Leu Tyr Leu Leu Asn Thr Met
545 550 555 560
gac gct gac tca ctt gtg tct aga tga 1707
Asp Ala Asp Ser Leu Val Ser Arg
565
<210>68
<211>568
<212>PRT
<213>人
<400>68
Met Val Leu Gly Pro Glu Gln Lys Met Ser Asp Asp Ser Val Ser Gly
1 5 10 15
Asp His Gly Glu Ser Ala Ser Leu Gly Asn Ile Asn Pro Ala Tyr Ser
20 25 30
Asn Pro Ser Leu Ser Gln Ser Pro Gly Asp Ser Glu Glu Tyr Phe Ala
35 40 45
Thr Tyr Phe Asn Glu Lys Ile Ser Ile Pro Glu Glu Glu Tyr Ser Cys
50 55 60
Phe Ser Phe Arg Lys Leu Trp Ala Phe Thr Gly Pro Gly Phe Leu Met
65 70 75 80
Ser Ile Ala Tyr Leu Asp Pro Gly Asn Ile Glu Ser Asp Leu Gln Ser
85 90 95
Gly Ala Val Ala Gly Phe Lys Leu Leu Trp Ile Leu Leu Leu Ala Thr
100 105 110
Leu Val Gly Leu Leu Leu Gln Arg Leu Ala Ala Arg Leu Gly Val Val
115 120 125
Thr Gly Leu His Leu Ala Glu Val Cys His Arg Gln Tyr Pro Lys Val
130 135 140
Pro Arg Val Ile Leu Trp Leu Met Val Glu Leu Ala Ile Ile Gly Ser
145 150 155 160
Asp Met Gln Glu Val Ile Gly Ser Ala Ile Ala Ile Asn Leu Leu Ser
165 170 175
Val Gly Arg Ile Pro Leu Trp Gly Gly Val Leu Ile Thr Ile Ala Asp
180 185 190
Thr Phe Val Phe Leu Phe Leu Asp Lys Tyr Gly Leu Arg Lys Leu Glu
195 200 205
Ala Phe Phe Gly Phe Leu Ile Thr Ile Met Ala Leu Thr Phe Gly Tyr
210 215 220
Glu Tyr Val Thr Val Lys Pro Ser Gln Ser Gln Val Leu Lys Gly Met
225 230 235 240
Phe Val Pro Ser Cys Ser Gly Cys Arg Thr Pro Gln Ile Glu Gln Ala
245 250 255
Val Gly Ile Val Gly Ala Val Ile Met Pro His Asn Met Tyr Leu His
260 265 270
Ser Ala Leu Val Lys Ser Arg Gln Val Asn Arg Asn Asn Lys Gln Glu
275 280 285
Val Arg Glu Ala Asn Lys Tyr Phe Phe Ile Glu Ser Cys Ile Ala Leu
290 295 300
Phe Val Ser Phe Ile Ile Asn Val Phe Val Val Ser Val Phe Ala Glu
305 310 315 320
Ala Phe Phe Gly Lys Thr Asn Glu Gln Val Val Glu Val Cys Thr Asn
325 330 335
Thr Ser Ser Pro His Ala Gly Leu Phe Pro Lys Asp Asn Ser Thr Leu
340 345 350
Ala Val Asp Ile Tyr Lys Gly Gly Val Val Leu Gly Cys Tyr Phe Gly
355 360 365
Pro Ala Ala Leu Tyr Ile Trp Ala Val Gly Ile Leu Ala Ala Gly Gln
370 375 380
Ser Ser Thr Met Thr Gly Thr Tyr Ser Gly Gln Phe Val Met Glu Gly
385 390 395 400
Phe Leu Asn Leu Lys Trp Ser Arg Phe Ala Arg Val Val Leu Thr Arg
405 410 415
Ser Ile Ala Ile Ile Pro Thr Leu Leu Val Ala Val Phe Gln Asp Val
420 425 430
Glu His Leu Thr Gly Met Asn Asp Phe Leu Asn Val Leu Gln Ser Leu
435 440 445
Gln Leu Pro Phe Ala Leu Ile Pro Ile Leu Thr Phe Thr Ser Leu Arg
450 455 460
Pro Val Met Ser Asp Phe Ala Asn Gly Leu Gly Trp Arg Ile Ala Gly
465 470 475 480
Gly Ile Leu Val Leu Ile Ile Cys Ser Ile Asn Met Tyr Phe Val Val
485 490 495
Val Tyr Val Arg Asp Leu Gly His Val Ala Leu Tyr Val Val Ala Ala
500 505 510
Val Val Ser Val Ala Tyr Leu Gly Phe Val Phe Tyr Leu Gly Trp Gln
515 520 525
Cys Leu Ile Ala Leu Gly Met Ser Phe Leu Asp Cys Gly His Thr Cys
530 535 540
His Leu Gly Leu Thr Ala Gln Pro Glu Leu Tyr Leu Leu Asn Thr Met
545 550 555 560
Asp Ala Asp Ser Leu Val Ser Arg
565
<210>69
<211>1521
<212>DNA
<213>果蝇
<220>
<221>CDS
<222>(1)..(1521)
<400>69
atg gtg gtg cgt ccg tac aac gat gag ctc cgg tac ctg gag aaa gtg 48
Met Val Val Arg Pro Tyr Asn Asp Glu Leu Arg Tyr Leu Glu Lys Val
1 5 10 15
agc gac cac tgc tgg cgc atc aag aag ggc ttc cag cca aat atg aat 96
Ser Asp His Cys Trp Arg Ile Lys Lys Gly Phe Gln Pro Asn Met Asn
20 25 30
gtg gag ggg tgt ttc tat gtg aac agc cgg ctg gag cgc ctg atg ctg 144
Val Glu Gly Cys Phe Tyr Val Asn Ser Arg Leu Glu Arg Leu Met Leu
35 40 45
gag gag ctg aag aac tcc tgt cgc ccg ggc gca gtg ggt ggc ttc ctg 192
Glu Glu Leu Lys Asn Ser Cys Arg Pro Gly Ala Val Gly Gly Phe Leu
50 55 60
cct ggc gtc aag cag ata gcc aat gtg gcc gcg ttg ccg ggc atc gtg 240
Pro Gly Val Lys Gln Ile Ala Asn Val Ala Ala Leu Pro Gly Ile Val
65 70 75 80
ggc agg tcc att gga ctg ccc gac att cat tcc ggc tac gga ttt gcc 288
Gly Arg Ser Ile Gly Leu Pro Asp Ile His Ser Gly Tyr Gly Phe Ala
85 90 95
atc ggg aac atg gct gct ttc gac atg aac gat ccg ctg tcc gtt gta 336
Ile Gly Asn Met Ala Ala Phe Asp Met Asn Asp Pro Leu Ser Val Val
100 105 110
agt ccc ggc ggc gtg ggt ttc gac atc aac tgt ggc gtg cgt ctg ctg 384
Ser Pro Gly Gly Val Gly Phe Asp Ile Asn Cys Gly Val Arg Leu Leu
115 120 125
cgc acg aat ctg tac gag aag gat gtg cag ccg gtg aag gag caa ctg 432
Arg Thr Asn Leu Tyr Glu Lys Asp Val Gln Pro Val Lys Glu Gln Leu
130 135 140
gcg cag tcc ctg ttc gat cac ata ccc gtg ggt gtg ggc tcc aag ggc 480
Ala Gln Ser Leu Phe Asp His Ile Pro Val Gly Val Gly Ser Lys Gly
145 150 155 160
atc ata ccc atg aat gcc cgc gat ctg gag gag gcc ctc gaa atg ggc 528
Ile Ile Pro Met Asn Ala Arg Asp Leu Glu Glu Ala Leu Glu Met Gly
165 170 175
atg gac tgg tcg ctg cgc gag gga tac gtg tgg gcg gag gac aag gag 576
Met Asp Trp Ser Leu Arg Glu Gly Tyr Val Trp Ala Glu Asp Lys Glu
180 185 190
cat tgc gag gag tac ggc cgc atg ctg aac gcc gat ccc gcc aag gtg 624
His Cys Glu Glu Tyr Gly Arg Met Leu Asn Ala Asp Pro Ala Lys Val
195 200 205
agc atg cgg gcc aag aag cga ggg ctg ccc cag ctg ggc act ctg ggt 672
Ser Met Arg Ala Lys Lys Arg Gly Leu Pro Gln Leu Gly Thr Leu Gly
210 215 220
gcg ggc aat cac tac gcc gag atc cag gtg gtg gac gaa atc tac gac 720
Ala Gly Asn His Tyr Ala Glu Ile Gln Val Val Asp Glu Ile Tyr Asp
225 230 235 240
aag tgg agc gcc tcc aag atg ggc atc gag gag aag ggc cag gtg gtg 768
Lys Trp Ser Ala Ser Lys Met Gly Ile Glu Glu Lys Gly Gln Val Val
245 250 255
gtg atg att cac tcg ggc agt cgt ggc ttc ggc cac cag gtc gct acc 816
Val Met Ile His Ser Gly Ser Arg Gly Phe Gly His Gln Val Ala Thr
260 265 270
gac gcc ctg gtc cag atg gag aag gcc atg aag cgg gac aag atc gag 864
Asp Ala Leu Val Gln Met Glu Lys Ala Met Lys Arg Asp Lys Ile Glu
275 280 285
acc aat gac cgg cag ctg gcc tgc gcc agg atc aat tcg gtg gag gga 912
Thr Asn Asp Arg Gln Leu Ala Cys Ala Arg Ile Asn Ser Val Glu Gly
290 295 300
cag gac tac ttg aag gcc atg gcg gcg gct gcg aac ttt gcc tgg gtg 960
Gln Asp Tyr Leu Lys Ala Met Ala Ala Ala Ala Asn Phe Ala Trp Val
305 310 315 320
aat cgc agc tcc atg aca ttc ctc acc cgt caa gcg ttt gcc aag atg 1008
Asn Arg Ser Ser Met Thr Phe Leu Thr Arg Gln Ala Phe Ala Lys Met
325 330 335
ttt aac acc aca ccc gat gat ctc gac atg cac gtt atc tat gac gtt 1056
Phe Asn Thr Thr Pro Asp Asp Leu Asp Met His Val Ile Tyr Asp Val
340 345 350
tcg cac aat att gcc aag gtg gag aac cac atg gtg gac ggc aag gag 1104
Ser His Asn Ile Ala Lys Val Glu Asn His Met Val Asp Gly Lys Glu
355 360 365
cgg aag ctg ttg gtt cac cgg aag ggc tcc acg cgc gcc ttc ccg cca 1152
Arg Lys Leu Leu Val His Arg Lys Gly Ser Thr Arg Ala Phe Pro Pro
370 375 380
cac cat ccc ctg atc cca gtg gac tat cag ctt acc ggg cag cca gtc 1200
His His Pro Leu Ile Pro Val Asp Tyr Gln Leu Thr Gly Gln Pro Val
385 390 395 400
ctc gtc ggt gga acc atg ggc act tgc agt tac gtg cta act gga acg 1248
Leu Val Gly Gly Thr Met Gly Thr Cys Ser Tyr Val Leu Thr Gly Thr
405 410 415
gag cag ggc atg cag gag acg ttc ggt agc act tgc cac gga gcg ggt 1296
Glu Gln Gly Met Gln Glu Thr Phe Gly Ser Thr Cys His Gly Ala Gly
420 425 430
cgt gca cta tct cga gcc aaa tcc cgg cgc aat ctg gac tac aag gat 1344
Arg Ala Leu Ser Arg Ala Lys Ser Arg Arg Asn Leu Asp Tyr Lys Asp
435 440 445
gtg ctg gac aag ctg gac cag ttg ggc atc gcc ata cgc gtg gcc tcg 1392
Val Leu Asp Lys Leu Asp Gln Leu Gly Ile Ala Ile Arg Val Ala Ser
450 455 460
ccc aaa ctg gtc atg gag gag gca ccc gaa tct tac aag gac gtg acc 1440
Pro Lys Leu Val Met Glu Glu Ala Pro Glu Ser Tyr Lys Asp Val Thr
465 470 475 480
gat gtg gtc gac acc tgt cac gca gct ggc atc agc aaa aag tgc atc 1488
Asp Val Val Asp Thr Cys His Ala Ala Gly Ile Ser Lys Lys Cys Ile
485 490 495
aag atg cgc cca att gca gtt atc aag ggc taa 1521
Lys Met Arg Pro Ile Ala Val Ile Lys Gly
500 505
<210>70
<211>506
<212>PRT
<213>果蝇
<400>70
Met Val Val Arg Pro Tyr Asn Asp Glu Leu Arg Tyr Leu Glu Lys Val
1 5 10 15
Ser Asp His Cys Trp Arg Ile Lys Lys Gly Phe Gln Pro Asn Met Asn
20 25 30
Val Glu Gly Cys Phe Tyr Val Asn Ser Arg Leu Glu Arg Leu Met Leu
35 40 45
Glu Glu Leu Lys Asn Ser Cys Arg Pro Gly Ala Val Gly Gly Phe Leu
50 55 60
Pro Gly Val Lys Gln Ile Ala Asn Val Ala Ala Leu Pro Gly Ile Val
65 70 75 80
Gly Arg Ser Ile Gly Leu Pro Asp Ile His Ser Gly Tyr Gly Phe Ala
85 90 95
Ile Gly Asn Met Ala Ala Phe Asp Met Asn Asp Pro Leu Ser Val Val
100 105 110
Ser Pro Gly Gly Val Gly Phe Asp Ile Asn Cys Gly Val Arg Leu Leu
115 120 125
Arg Thr Asn Leu Tyr Glu Lys Asp Val Gln Pro Val Lys Glu Gln Leu
130 135 140
Ala Gln Ser Leu Phe Asp His Ile Pro Val Gly Val Gly Ser Lys Gly
145 150 155 160
Ile Ile Pro Met Asn Ala Arg Asp Leu Glu Glu Ala Leu Glu Met Gly
165 170 175
Met Asp Trp Ser Leu Arg Glu Gly Tyr Val Trp Ala Glu Asp Lys Glu
180 185 190
His Cys Glu Glu Tyr Gly Arg Met Leu Asn Ala Asp Pro Ala Lys Val
195 200 205
Ser Met Arg Ala Lys Lys Arg Gly Leu Pro Gln Leu Gly Thr Leu Gly
210 215 220
Ala Gly Asn His Tyr Ala Glu Ile Gln Val Val Asp Glu Ile Tyr Asp
225 230 235 240
Lys Trp Ser Ala Ser Lys Met Gly Ile Glu Glu Lys Gly Gln Val Val
245 250 255
Val Met Ile His Ser Gly Ser Arg Gly Phe Gly His Gln Val Ala Thr
260 265 270
Asp Ala Leu Val Gln Met Glu Lys Ala Met Lys Arg Asp Lys Ile Glu
275 280 285
Thr Asn Asp Arg Gln Leu Ala Cys Ala Arg Ile Asn Ser Val Glu Gly
290 295 300
Gln Asp Tyr Leu Lys Ala Met Ala Ala Ala Ala Asn Phe Ala Trp Val
305 310 315 320
Asn Arg Ser Ser Met Thr Phe Leu Thr Arg Gln Ala Phe Ala Lys Met
325 330 335
Phe Asn Thr Thr Pro Asp Asp Leu Asp Met His Val Ile Tyr Asp Val
340 345 350
Ser His Asn Ile Ala Lys Val Glu Asn His Met Val Asp Gly Lys Glu
355 360 365
Arg Lys Leu Leu Val His Arg Lys Gly Ser Thr Arg Ala Phe Pro Pro
370 375 380
His His Pro Leu Ile Pro Val Asp Tyr Gln Leu Thr Gly Gln Pro Val
385 390 395 400
Leu Val Gly Gly Thr Met Gly Thr Cys Ser Tyr Val Leu Thr Gly Thr
405 410 415
Glu Gln Gly Met Gln Glu Thr Phe Gly Ser Thr Cys His Gly Ala Gly
420 425 430
Arg Ala Leu Ser Arg Ala Lys Ser Arg Arg Asn Leu Asp Tyr Lys Asp
435 440 445
Val Leu Asp Lys Leu Asp Gln Leu Gly Ile Ala Ile Arg Val Ala Ser
450 455 460
Pro Lys Leu Val Met Glu Glu Ala Pro Glu Ser Tyr Lys Asp Val Thr
465 470 475 480
Asp Val Val Asp Thr Cys His Ala Ala Gly Ile Ser Lys Lys Cys Ile
485 490 495
Lys Met Arg Pro Ile Ala Val Ile Lys Gly
500 505
<210>71
<211>1518
<212>DNA
<213>斑马鱼
<220>
<221>CDS
<222>(1)..(1518)
<400>71
atg agt cgc tct tac aac gat gag ctc cag tat ctg gat aaa ata cac 48
Met Ser Arg Ser Tyr Asn Asp Glu Leu Gln Tyr Leu Asp Lys Ile His
1 5 10 15
aaa aac tgc tgg cgg atc aag aag ggt ttc gtg ccg aat atg ctg gtg 96
Lys Asn Cys Trp Arg Ile Lys Lys Gly Phe Val Pro Asn Met Leu Val
20 25 30
gaa gga gtg ttt tat gtc aat gac ccg ctg gaa aag ctg atg ttc gag 144
Glu Gly Val Phe Tyr Val Asn Asp Pro Leu Glu Lys Leu Met Phe Glu
35 40 45
gag ctg aga aac gcc tgt cgc gga gga ggg ttt gga ggt ttc tta cct 192
Glu Leu Arg Asn Ala Cys Arg Gly Gly Gly Phe Gly Gly Phe Leu Pro
50 55 60
gcg atg aag cag att ggg aat gtg gcc gct ctg cca gga atc gtg cac 240
Ala Met Lys Gln Ile Gly Asn Val Ala Ala Leu Pro Gly Ile Val His
65 70 75 80
cgg tcg atc ggt tta ccg gac gtt cac tca gga tac gga ttc gct atc 288
Arg Ser Ile Gly Leu Pro Asp Val His Ser Gly Tyr Gly Phe Ala Ile
85 90 95
ggg aac atg gca gcg ttc gac atg gag aat ccg gac gca gtc gtc tct 336
Gly Asn Met Ala Ala Phe Asp Met Glu Asn Pro Asp Ala Val Val Ser
100 105 110
cca ggc ggt gtg ggt ttc gat att aac tgt ggt gtt cgt ctg ctg cgc 384
Pro Gly Gly Val Gly Phe Asp Ile Asn Cys Gly Val Arg Leu Leu Arg
115 120 125
aca aac ctg gat gag ggc gac gtt cag ccg gtg aag gag cag ctg gca 432
Thr Asn Leu Asp Glu Gly Asp Val Gln Pro Val Lys Glu Gln Leu Ala
130 135 140
cag tct ctc ttc gac cac atc cct gtc gga gtc ggc tcc aag ggc gtc 480
Gln Ser Leu Phe Asp His Ile Pro Val Gly Val Gly Ser Lys Gly Val
145 150 155 160
att cct atg ggt gca aag gac ctg gag gag gcg ttg gag atg ggt gtg 528
Ile Pro Met Gly Ala Lys Asp Leu Glu Glu Ala Leu Glu Met Gly Val
165 170 175
gac tgg tct ctg agg gag gga tat gcc tgg gcg gag gat aaa gag cac 576
Asp Trp Ser Leu Arg Glu Gly Tyr Ala Trp Ala Glu Asp Lys Glu His
180 185 190
tgt gag gag tac gga cgc atg ctg cag gcc gac cca aac aaa gtc tcc 624
Cys Glu Glu Tyr Gly Arg Met Leu Gln Ala Asp Pro Asn Lys Val Ser
195 200 205
tcc aaa gcc aag aag aga gga ctg cca cag ttg gga act ctg ggt gca 672
Ser Lys Ala Lys Lys Arg Gly Leu Pro Gln Leu Gly Thr Leu Gly Ala
210 215 220
gga aac cac tac gca gag att cag gtg gtg gac gag atc tac aat gat 720
Gly Asn His Tyr Ala Glu Ile Gln Val Val Asp Glu Ile Tyr Asn Asp
225 230 235 240
tac gcc gcc aag aag atg ggc atc gat cat aaa ggg cag gtg tgt gtg 768
Tyr Ala Ala Lys Lys Met Gly Ile Asp His Lys Gly Gln Val Cys Val
245 250 255
atg atc cac agc ggc agc cga gga ctc gga cat cag gtg gcc acc gac 816
Met Ile His Ser Gly Ser Arg Gly Leu Gly His Gln Val Ala Thr Asp
260 265 270
gct ctg gtg gcg atg gag aag gcc atg aag cgc gac cgc atc aca gta 864
Ala Leu Val Ala Met Glu Lys Ala Met Lys Arg Asp Arg Ile Thr Val
275 280 285
aac gac cgg cag cta gcg tgc gcg cgc atc acg tca gaa gag gga cag 912
Asn Asp Arg Gln Leu Ala Cys Ala Arg Ile Thr Ser Glu Glu Gly Gln
290 295 300
gat tat ctg aag gga atg gcg gca gca gga aac tac gcc tgg gtc aac 960
Asp Tyr Leu Lys Gly Met Ala Ala Ala Gly Asn Tyr Ala Trp Val Asn
305 310 315 320
cga tcc tcc atg acc ttc ctc aca cga cag gcg ttc tcc aaa gtg ttc 1008
Arg Ser Ser Met Thr Phe Leu Thr Arg Gln Ala Phe Ser Lys Val Phe
325 330 335
agc acc aca cca gat gat ctg gac atg cac gtg atc tac gac gtc tcg 1056
Ser Thr Thr Pro Asp Asp Leu Asp Met His Val Ile Tyr Asp Val Ser
340 345 350
cac aac atc gcc aaa gtg gag gag cac atg gtg gac ggc cgg cag aaa 1104
His Asn Ile Ala Lys Val Glu Glu His Met Val Asp Gly Arg Gln Lys
355 360 365
aca ctg ctg gtg cat agg aag ggc tcc acc aga gcg ttt cct cca cac 1152
Thr Leu Leu Val His Arg Lys Gly Ser Thr Arg Ala Phe Pro Pro His
370 375 380
cat cca ctc ata cct gta gac tat cag ctg acc ggt cag cca gtc ctg 1200
His Pro Leu Ile Pro Val Asp Tyr Gln Leu Thr Gly Gln Pro Val Leu
385 390 395 400
att gga gga acc atg ggc acc tgc agt tac gtg ctc aca ggc aca gag 1248
Ile Gly Gly Thr Met Gly Thr Cys Ser Tyr Val Leu Thr Gly Thr Glu
405 410 415
cag ggc atg aca gag acg ttc ggc acc aca tgt cac ggc gct ggc cga 1296
Gln Gly Met Thr Glu Thr Phe Gly Thr Thr Cys His Gly Ala Gly Arg
420 425 430
gct tta tcc aga gcc aaa tcc aga cgc aac ctg gac ttc cag gat gtt 1344
Ala Leu Ser Arg Ala Lys Ser Arg Arg Asn Leu Asp Phe Gln Asp Val
435 440 445
ctg gat aaa ctg gca gac atg ggc atc gct att aga gtg gcg tca ccg 1392
Leu Asp Lys Leu Ala Asp Met Gly Ile Ala Ile Arg Val Ala Ser Pro
450 455 460
aag ctg gtg atg gag gag gct ccc gag tcc tac aag aac gtg aca gac 1440
Lys Leu Val Met Glu Glu Ala Pro Glu Ser Tyr Lys Asn Val Thr Asp
465 470 475 480
gtg gtg aac aca tgc cat gat gcc ggc atc agc aaa aaa gcc atc aaa 1488
Val Val Asn Thr Cys His Asp Ala Gly Ile Ser Lys Lys Ala Ile Lys
485 490 495
ctc aga ccc atc gct gtg att aaa ggt taa 1518
Leu Arg Pro Ile Ala Val Ile Lys Gly
500 505
<210>72
<211>505
<212>PRT
<213>斑马鱼
<400>72
Met Ser Arg Ser Tyr Asn Asp Glu Leu Gln Tyr Leu Asp Lys Ile His
1 5 10 15
Lys Asn Cys Trp Arg Ile Lys Lys Gly Phe Val Pro Asn Met Leu Val
20 25 30
Glu Gly Val Phe Tyr Val Asn Asp Pro Leu Glu Lys Leu Met Phe Glu
35 40 45
Glu Leu Arg Asn Ala Cys Arg Gly Gly Gly Phe Gly Gly Phe Leu Pro
50 55 60
Ala Met Lys Gln Ile Gly Asn Val Ala Ala Leu Pro Gly Ile Val His
65 70 75 80
Arg Ser Ile Gly Leu Pro Asp Val His Ser Gly Tyr Gly Phe Ala Ile
85 90 95
Gly Asn Met Ala Ala Phe Asp Met Glu Asn Pro Asp Ala Val Val Ser
100 105 110
Pro Gly Gly Val Gly Phe Asp Ile Asn Cys Gly Val Arg Leu Leu Arg
115 120 125
Thr Asn Leu Asp Glu Gly Asp Val Gln Pro Val Lys Glu Gln Leu Ala
130 135 140
Gln Ser Leu Phe Asp His Ile Pro Val Gly Val Gly Ser Lys Gly Val
145 150 155 160
Ile Pro Met Gly Ala Lys Asp Leu Glu Glu Ala Leu Glu Met Gly Val
165 170 175
Asp Trp Ser Leu Arg Glu Gly Tyr Ala Trp Ala Glu Asp Lys Glu His
180 185 190
Cys Glu Glu Tyr Gly Arg Met Leu Gln Ala Asp Pro Asn Lys Val Ser
195 200 205
Ser Lys Ala Lys Lys Arg Gly Leu Pro Gln Leu Gly Thr Leu Gly Ala
210 215 220
Gly Asn His Tyr Ala Glu Ile Gln Val Val Asp Glu Ile Tyr Asn Asp
225 230 235 240
Tyr Ala Ala Lys Lys Met Gly Ile Asp His Lys Gly Gln Val Cys Val
245 250 255
Met Ile His Ser Gly Ser Arg Gly Leu Gly His Gln Val Ala Thr Asp
260 265 270
Ala Leu Val Ala Met Glu Lys Ala Met Lys Arg Asp Arg Ile Thr Val
275 280 285
Asn Asp Arg Gln Leu Ala Cys Ala Arg Ile Thr Ser Glu Glu Gly Gln
290 295 300
Asp Tyr Leu Lys Gly Met Ala Ala Ala Gly Asn Tyr Ala Trp Val Asn
305 310 315 320
Arg Ser Ser Met Thr Phe Leu Thr Arg Gln Ala Phe Ser Lys Val Phe
325 330 335
Ser Thr Thr Pro Asp Asp Leu Asp Met His Val Ile Tyr Asp Val Ser
340 345 350
His Asn Ile Ala Lys Val Glu Glu His Met Val Asp Gly Arg Gln Lys
355 360 365
Thr Leu Leu Val His Arg Lys Gly Ser Thr Arg Ala Phe Pro Pro His
370 375 380
His Pro Leu Ile Pro Val Asp Tyr Gln Leu Thr Gly Gln Pro Val Leu
385 390 395 400
Ile Gly Gly Thr Met Gly Thr Cys Ser Tyr Val Leu Thr Gly Thr Glu
405 410 415
Gln Gly Met Thr Glu Thr Phe Gly Thr Thr Cys His Gly Ala Gly Arg
420 425 430
Ala Leu Ser Arg Ala Lys Ser Arg Arg Asn Leu Asp Phe Gln Asp Val
435 440 445
Leu Asp Lys Leu Ala Asp Met Gly Ile Ala Ile Arg Val Ala Ser Pro
450 455 460
Lys Leu Val Met Glu Glu Ala Pro Glu Ser Tyr Lys Asn Val Thr Asp
465 470 475 480
Val Val Asn Thr Cys His Asp Ala Gly Ile Ser Lys Lys Ala Ile Lys
485 490 495
Leu Arg Pro Ile Ala Val Ile Lys Gly
500 505
<210>73
<211>1518
<212>DNA
<213>牛
<220>
<221>CDS
<222>(1)..(1518)
<400>73
atg agt cgc agt tat aat gat gag ctg cag ttc ttg gaa aag atc agt 48
Met Ser Arg Ser Tyr Asn Asp Glu Leu Gln Phe Leu Glu Lys Ile Ser
1 5 10 15
aag aac tgc tgg aga atc aag aag ggc ttc gtg ccc aac atg cag gtt 96
Lys Asn Cys Trp Arg Ile Lys Lys Gly Phe Val Pro Asn Met Gln Val
20 25 30
gaa gga gtt ttc tat gtg aat gat tct ctg gaa aaa tta atg ttt gaa 144
Glu Gly Val Phe Tyr Val Asn Asp Ser Leu Glu Lys Leu Met Phe Glu
35 40 45
gaa tta agg aat gcc tgt cga ggt ggt ggt gtt ggt ggc ttc ctg cca 192
Glu Leu Arg Asn Ala Cys Arg Gly Gly Gly Val Gly Gly Phe Leu Pro
50 55 60
gcc atg aaa caa att ggc aat gtg gcc gcc ctg cct ggg att gtt cat 240
Ala Met Lys Gln Ile Gly Asn Val Ala Ala Leu Pro Gly Ile Val His
65 70 75 80
cga tcc atc ggt ctt cct gat gtc cat tca ggt tat ggg ttt gct att 288
Arg Ser Ile Gly Leu Pro Asp Val His Ser Gly Tyr Gly Phe Ala Ile
85 90 95
gga aat atg gca gcc ttt gat atg aac gac cct gaa gca gtg gta tcc 336
Gly Asn Met Ala Ala Phe Asp Met Asn Asp Pro Glu Ala Val Val Ser
100 105 110
cca ggt ggt gtt ggg ttt gac att aac tgt ggt gtc cgc ttg ctg aga 384
Pro Gly Gly Val Gly Phe Asp Ile Asn Cys Gly Val Arg Leu Leu Arg
115 120 125
acc aat tta gat gaa agt gat gtt cag cct gtg aaa gag caa ctt gcc 432
Thr Asn Leu Asp Glu Ser Asp Val Gln Pro Val Lys Glu Gln Leu Ala
130 135 140
caa gct atg ttt gac cac att cct gtg gga gtg ggg tca aaa ggt gtc 480
Gln Ala Met Phe Asp His Ile Pro Val Gly Val Gly Ser Lys Gly Val
145 150 155 160
atc cca atg aat gcc aaa gac ttg gag gag gcc ttg gag atg ggt gtg 528
Ile Pro Met Asn Ala Lys Asp Leu Glu Glu Ala Leu Glu Met Gly Val
165 170 175
gac tgg tcc ctg aga gaa ggc tat gcc tgg gca gag gac aag gag cac 576
Asp Trp Ser Leu Arg Glu Gly Tyr Ala Trp Ala Glu Asp Lys Glu His
180 185 190
tgt gag gag tat gga agg atg ctg caa gct gat ccc aat aaa gtc tca 624
Cys Glu Glu Tyr Gly Arg Met Leu Gln Ala Asp Pro Asn Lys Val Ser
195 200 205
gcc agg gct aaa aaa aga ggc ctt ccc cag ttg ggg act ctg gga gca 672
Ala Arg Ala Lys Lys Arg Gly Leu Pro Gln Leu Gly Thr Leu Gly Ala
210 215 220
ggc aac cac tat gca gaa atc cag gtt gtg gat gag att ttc aac gag 720
Gly Asn His Tyr Ala Glu Ile Gln Val Val Asp Glu Ile Phe Asn Glu
225 230 235 240
tat gct gct aag aaa atg ggc att gac cat aag gga cag gtg tgt gtg 768
Tyr Ala Ala Lys Lys Met Gly Ile Asp His Lys Gly Gln Val Cys Val
245 250 255
atg atc cac agt gga agc aga ggc ttg ggc cac caa gtt gcc aca gat 816
Met Ile His Ser Gly Ser Arg Gly Leu Gly His Gln Val Ala Thr Asp
260 265 270
gca ctt gta gct atg gaa aaa gcc atg aag aga gac aag att ata gtc 864
Ala Leu Val Ala Met Glu Lys Ala Met Lys Arg Asp Lys Ile Ile Val
275 280 285
aat gac cgt cag ttg gct tgt gct cga att gct tcc cca gag ggt cag 912
Asn Asp Arg Gln Leu Ala Cys Ala Arg Ile Ala Ser Pro Glu Gly Gln
290 295 300
gac tac ctg aag gga atg gca gcg gct ggg aac tat gcc tgg gtc aac 960
Asp Tyr Leu Lys Gly Met Ala Ala Ala Gly Asn Tyr Ala Trp Val Asn
305 310 315 320
cgc tct tcc atg acc ttc tta acc cgt cag gct ttt gcc aag gtc ttc 1008
Arg Ser Ser Met Thr Phe Leu Thr Arg Gln Ala Phe Ala Lys Val Phe
325 330 335
aac aca acc cct gat gac ttg gac ctg cat gtg atc tat gat gtt tct 1056
Asn Thr Thr Pro Asp Asp Leu Asp Leu His Val Ile Tyr Asp Val Ser
340 345 350
cac aat att gcc aaa gta gaa cag cat gtg gtg gac ggg aag gag cgg 1104
His Asn Ile Ala Lys Val Glu Gln His Val Val Asp Gly Lys Glu Arg
355 360 365
act ctg tta gta cac agg aag ggg tcc acc cga gcc ttc cct cct cac 1152
Thr Leu Leu Val His Arg Lys Gly Ser Thr Arg Ala Phe Pro Pro His
370 375 380
cat ccc ctc att gcg gtt gat tac caa ctt acc gga caa cca gtg ctc 1200
His Pro Leu Ile Ala Val Asp Tyr Gln Leu Thr Gly Gln Pro Val Leu
385 390 395 400
att ggt ggc acc atg gga acc tgt agc tat gtt ctt act ggt act gag 1248
Ile Gly Gly Thr Met Gly Thr Cys Ser Tyr Val Leu Thr Gly Thr Glu
405 410 415
cag ggc atg act gaa acc ttt gga aca act tgt cat gga gcg ggc cgt 1296
Gln Gly Met Thr Glu Thr Phe Gly Thr Thr Cys His Gly Ala Gly Arg
420 425 430
gca ctg tcc cga gca aag tca aga cgt aat tta gat ttc cag gat gtc 1344
Ala Leu Ser Arg Ala Lys Ser Arg Arg Asn Leu Asp Phe Gln Asp Val
435 440 445
ctc gac aaa ttg gca gac atg gga att gca atc cgt gtc gcc tca ccc 1392
Leu Asp Lys Leu Ala Asp Met Gly Ile Ala Ile Arg Val Ala Ser Pro
450 455 460
aag ctg gta atg gaa gag gcc cct gag tcc tat aag aac gtg acg gat 1440
Lys Leu Val Met Glu Glu Ala Pro Glu Ser Tyr Lys Asn Val Thr Asp
465 470 475 480
gtg gtg aac acc tgc cat gat gcc gga atc agc aag aag gcc att aaa 1488
Val Val Asn Thr Cys His Asp Ala Gly Ile Ser Lys Lys Ala Ile Lys
485 490 495
ctg agg cca att gct gtt atc aaa gga tag 1518
Leu Arg Pro Ile Ala Val Ile Lys Gly
500 505
<210>74
<211>505
<212>PRT
<213>牛
<400>74
Met Ser Arg Ser Tyr Asn Asp Glu Leu Gln Phe Leu Glu Lys Ile Ser
1 5 10 15
Lys Asn Cys Trp Arg Ile Lys Lys Gly Phe Val Pro Asn Met Gln Val
20 25 30
Glu Gly Val Phe Tyr Val Asn Asp Ser Leu Glu Lys Leu Met Phe Glu
35 40 45
Glu Leu Arg Asn Ala Cys Arg Gly Gly Gly Val Gly Gly Phe Leu Pro
50 55 60
Ala Met Lys Gln Ile Gly Asn Val Ala Ala Leu Pro Gly Ile Val His
65 70 75 80
Arg Ser Ile Gly Leu Pro Asp Val His Ser Gly Tyr Gly Phe Ala Ile
85 90 95
Gly Asn Met Ala Ala Phe Asp Met Asn Asp Pro Glu Ala Val Val Ser
100 105 110
Pro Gly Gly Val Gly Phe Asp Ile Asn Cys Gly Val Arg Leu Leu Arg
115 120 125
Thr Asn Leu Asp Glu Ser Asp Val Gln Pro Val Lys Glu Gln Leu Ala
130 135 140
Gln Ala Met Phe Asp His Ile Pro Val Gly Val Gly Ser Lys Gly Val
145 150 155 160
Ile Pro Met Asn Ala Lys Asp Leu Glu Glu Ala Leu Glu Met Gly Val
165 170 175
Asp Trp Ser Leu Arg Glu Gly Tyr Ala Trp Ala Glu Asp Lys Glu His
180 185 190
Cys Glu Glu Tyr Gly Arg Met Leu Gln Ala Asp Pro Asn Lys Val Ser
195 200 205
Ala Arg Ala Lys Lys Arg Gly Leu Pro Gln Leu Gly Thr Leu Gly Ala
210 215 220
Gly Asn His Tyr Ala Glu Ile Gln Val Val Asp Glu Ile Phe Asn Glu
225 230 235 240
Tyr Ala Ala Lys Lys Met Gly Ile Asp His Lys Gly Gln Val Cys Val
245 250 255
Met Ile His Ser Gly Ser Arg Gly Leu Gly His Gln Val Ala Thr Asp
260 265 270
Ala Leu Val Ala Met Glu Lys Ala Met Lys Arg Asp Lys Ile Ile Val
275 280 285
Asn Asp Arg Gln Leu Ala Cys Ala Arg Ile Ala Ser Pro Glu Gly Gln
290 295 300
Asp Tyr Leu Lys Gly Met Ala Ala Ala Gly Asn Tyr Ala Trp Val Asn
305 310 315 320
Arg Ser Ser Met Thr Phe Leu Thr Arg Gln Ala Phe Ala Lys Val Phe
325 330 335
Asn Thr Thr Pro Asp Asp Leu Asp Leu His Val Ile Tyr Asp Val Ser
340 345 350
His Asn Ile Ala Lys Val Glu Gln His Val Val Asp Gly Lys Glu Arg
355 360 365
Thr Leu Leu Val His Arg Lys Gly Ser Thr Arg Ala Phe Pro Pro His
370 375 380
His Pro Leu Ile Ala Val Asp Tyr Gln Leu Thr Gly Gln Pro Val Leu
385 390 395 400
Ile Gly Gly Thr Met Gly Thr Cys Ser Tyr Val Leu Thr Gly Thr Glu
405 410 415
Gln Gly Met Thr Glu Thr Phe Gly Thr Thr Cys His Gly Ala Gly Arg
420 425 430
Ala Leu Ser Arg Ala Lys Ser Arg Arg Asn Leu Asp Phe Gln Asp Val
435 440 445
Leu Asp Lys Leu Ala Asp Met Gly Ile Ala Ile Arg Val Ala Ser Pro
450 455 460
Lys Leu Val Met Glu Glu Ala Pro Glu Ser Tyr Lys Asn Val Thr Asp
465 470 475 480
Val Val Asn Thr Cys His Asp Ala Gly Ile Ser Lys Lys Ala Ile Lys
485 490 495
Leu Arg Pro Ile Ala Val Ile Lys Gly
500 505
<210>75
<211>1518
<212>DNA
<213>小鼠
<220>
<221>CDS
<222>(1)..(1518)
<400>75
atg agt cgt aac tac aac gat gag cta cag ttc ttg gac aag atc aat 48
Met Ser Arg Asn Tyr Asn Asp Glu Leu Gln Phe Leu Asp Lys Ile Asn
1 5 10 15
aaa aac tgc tgg agg atc aag aag ggc ttt gtg ccc aac atg cag gtt 96
Lys Asn Cys Trp Arg Ile Lys Lys Gly Phe Val Pro Asn Met Gln Val
20 25 30
gaa gga gtg ttt tat gtg aat gat gct ctg gaa aaa cta atg ttt gag 144
Glu Gly Val Phe Tyr Val Asn Asp Ala Leu Glu Lys Leu Met Phe Glu
35 40 45
gaa tta agg aac gcc tgt cga ggt ggt ggt gtt ggt ggc ttt ctg cca 192
Glu Leu Arg Asn Ala Cys Arg Gly Gly Gly Val Gly Gly Phe Leu Pro
50 55 60
gcc atg aag cag att ggc aat gtg gca gcc ctg cct gga ata gtt cat 240
Ala Met Lys Gln Ile Gly Asn Val Ala Ala Leu Pro Gly Ile Val His
65 70 75 80
cgg tct atc ggg ctt cct gat gtc cat tca ggc tat ggg ttt gcc ata 288
Arg Ser Ile Gly Leu Pro Asp Val His Ser Gly Tyr Gly Phe Ala Ile
85 90 95
ggg aac atg gct gcc ttt gat atg aat gac cct gag gcc gtt gta tcc 336
Gly Asn Met Ala Ala Phe Asp Met Asn Asp Pro Glu Ala Val Val Ser
100 105 110
cca ggt ggt gtc gga ttt gat att aac tgt ggt gtc cgc ttg cta aga 384
Pro Gly Gly Val Gly Phe Asp Ile Asn Cys Gly Val Arg Leu Leu Arg
115 120 125
acc aat tta gat gag agc gat gta cag cct gtg aag gaa caa ctt gcc 432
Thr Asn Leu Asp Glu Ser Asp Val Gln Pro Val Lys Glu Gln Leu Ala
130 135 140
caa gct atg ttt gac cac atc cct gtt ggg gtg gga tca aaa ggt gtc 480
Gln Ala Met Phe Asp His Ile Pro Val Gly Val Gly Ser Lys Gly Val
145 150 155 160
att cca atg aat gcc aaa gac ttg gag gag gca ttg gag atg ggg gtg 528
Ile Pro Met Asn Ala Lys Asp Leu Glu Glu Ala Leu Glu Met Gly Val
165 170 175
gac tgg tcc ctg agg gaa ggc tat gcc tgg gct gaa gac aag gag cac 576
Asp Trp Ser Leu Arg Glu Gly Tyr Ala Trp Ala Glu Asp Lys Glu His
180 185 190
tgt gag gag tat gga agg atg ctg caa gcc gac ccc aat aag gtc tca 624
Cys Glu Glu Tyr Gly Arg Met Leu Gln Ala Asp Pro Asn Lys Val Ser
195 200 205
ccc agg gca aag aaa agg ggc ctt cct cag ttg ggg acc ctg gga gca 672
Pro Arg Ala Lys Lys Arg Gly Leu Pro Gln Leu Gly Thr Leu Gly Ala
210 215 220
ggc aac cat tat gca gaa atc cag gtt gta gat gag att ttc aat gag 720
Gly Asn His Tyr Ala Glu Ile Gln Val Val Asp Glu Ile Phe Asn Glu
225 230 235 240
tat gcc gcc aag aag atg ggc atc gac cat aag gga cag gtg tgt gtg 768
Tyr Ala Ala Lys Lys Met Gly Ile Asp His Lys Gly Gln Val Cys Val
245 250 255
atg atc cac agt gga agc aga ggc ttg ggc cac caa gta gct aca gat 816
Met Ile His Ser Gly Ser Arg Gly Leu Gly His Gln Val Ala Thr Asp
260 265 270
gca ctg gta gct atg gaa aag gcc atg aag aga gac aag att ata gtc 864
Ala Leu Val Ala Met Glu Lys Ala Met Lys Arg Asp Lys Ile Ile Val
275 280 285
aat gac cgg cag ttg gct tgt gct cgg att gca tcc cca gag gga caa 912
Asn Asp Arg Gln Leu Ala Cys Ala Arg Ile Ala Ser Pro Glu Gly Gln
290 295 300
gac tat cta aag gga atg gct gca gct gga aac tac gcc tgg gtt aac 960
Asp Tyr Leu Lys Gly Met Ala Ala Ala Gly Asn Tyr Ala Trp Val Asn
305 310 315 320
cgc tcc tct atg acc ttc tta acc cgt cag gct ttt gcc aaa gtc ttc 1008
Arg Ser Ser Met Thr Phe Leu Thr Arg Gln Ala Phe Ala Lys Val Phe
325 330 335
aac aca acc cct gat gac ctg gac ctg cat gtg atc tat gat gtg tcg 1056
Asn Thr Thr Pro Asp Asp Leu Asp Leu His Val Ile Tyr Asp Val Ser
340 345 350
cac aat atc gcc aaa gtg gag cag cac gtg gtg gat ggg aag gaa cgg 1104
His Asn Ile Ala Lys Val Glu Gln His Val Val Asp Gly Lys Glu Arg
355 360 365
acg ctg ctg gtg cac agg aag gga tcc acc cgt gct ttc ccg cct cac 1152
Thr Leu Leu Val His Arg Lys Gly Ser Thr Arg Ala Phe Pro Pro His
370 375 380
cac ccc ctc att gct gtg gat tat caa ctc aca gga caa cca gtg ctt 1200
His Pro Leu Ile Ala Val Asp Tyr Gln Leu Thr Gly Gln Pro Val Leu
385 390 395 400
att ggt ggc acc atg ggg acc tgt agt tac gtt ctg act ggc act gaa 1248
Ile Gly Gly Thr Met Gly Thr Cys Ser Tyr Val Leu Thr Gly Thr Glu
405 410 415
caa ggc atg act gag acc ttt gga aca acc tgt cat gga gcg ggc cgt 1296
Gln Gly Met Thr Glu Thr Phe Gly Thr Thr Cys His Gly Ala Gly Arg
420 425 430
gct ttg tcc aga gca aaa tca cgt cgt aac tta gat ttc caa gat gtc 1344
Ala Leu Ser Arg Ala Lys Ser Arg Arg Asn Leu Asp Phe Gln Asp Val
435 440 445
tta gac aaa ctg gca gac atg gga att gca atc cgg gtt gct tcc ccc 1392
Leu Asp Lys Leu Ala Asp Met Gly Ile Ala Ile Arg Val Ala Ser Pro
450 455 460
aag ctg gtt atg gaa gag gca cca gag tcc tat aag aat gtg aca gac 1440
Lys Leu Val Met Glu Glu Ala Pro Glu Ser Tyr Lys Asn Val Thr Asp
465 470 475 480
gtc gtg aac acc tgc cat gat gct ggg atc agc aag aag gcc att aaa 1488
Val Val Asn Thr Cys His Asp Ala Gly Ile Ser Lys Lys Ala Ile Lys
485 490 495
ctg aga cca att gct gtt att aaa ggg tag 1518
Leu Arg Pro Ile Ala Val Ile Lys Gly
500 505
<210>76
<211>505
<212>PRT
<213>小鼠
<400>76
Met Ser Arg Asn Tyr Asn Asp Glu Leu Gln Phe Leu Asp Lys Ile Asn
1 5 10 15
Lys Asn Cys Trp Arg Ile Lys Lys Gly Phe Val Pro Asn Met Gln Val
20 25 30
Glu Gly Val Phe Tyr Val Asn Asp Ala Leu Glu Lys Leu Met Phe Glu
35 40 45
Glu Leu Arg Asn Ala Cys Arg Gly Gly Gly Val Gly Gly Phe Leu Pro
50 55 60
Ala Met Lys Gln Ile Gly Asn Val Ala Ala Leu Pro Gly Ile Val His
65 70 75 80
Arg Ser Ile Gly Leu Pro Asp Val His Ser Gly Tyr Gly Phe Ala Ile
85 90 95
Gly Asn Met Ala Ala Phe Asp Met Asn Asp Pro Glu Ala Val Val Ser
100 105 110
Pro Gly Gly Val Gly Phe Asp Ile Asn Cys Gly Val Arg Leu Leu Arg
115 120 125
Thr Asn Leu Asp Glu Ser Asp Val Gln Pro Val Lys Glu Gln Leu Ala
130 135 140
Gln Ala Met Phe Asp His Ile Pro Val Gly Val Gly Ser Lys Gly Val
145 150 155 160
Ile Pro Met Asn Ala Lys Asp Leu Glu Glu Ala Leu Glu Met Gly Val
165 170 175
Asp Trp Ser Leu Arg Glu Gly Tyr Ala Trp Ala Glu Asp Lys Glu His
180 185 190
Cys Glu Glu Tyr Gly Arg Met Leu Gln Ala Asp Pro Asn Lys Val Ser
195 200 205
Pro Arg Ala Lys Lys Arg Gly Leu Pro Gln Leu Gly Thr Leu Gly Ala
210 215 220
Gly Asn His Tyr Ala Glu Ile Gln Val Val Asp Glu Ile Phe Asn Glu
225 230 235 240
Tyr Ala Ala Lys Lys Met Gly Ile Asp His Lys Gly Gln Val Cys Val
245 250 255
Met Ile His Ser Gly Ser Arg Gly Leu Gly His Gln Val Ala Thr Asp
260 265 270
Ala Leu Val Ala Met Glu Lys Ala Met Lys Arg Asp Lys Ile Ile Val
275 280 285
Asn Asp Arg Gln Leu Ala Cys Ala Arg Ile Ala Ser Pro Glu Gly Gln
290 295 300
Asp Tyr Leu Lys Gly Met Ala Ala Ala Gly Asn Tyr Ala Trp Val Asn
305 310 315 320
Arg Ser Ser Met Thr Phe Leu Thr Arg Gln Ala Phe Ala Lys Val Phe
325 330 335
Asn Thr Thr Pro Asp Asp Leu Asp Leu His Val Ile Tyr Asp Val Ser
340 345 350
His Asn Ile Ala Lys Val Glu Gln His Val Val Asp Gly Lys Glu Arg
355 360 365
Thr Leu Leu Val His Arg Lys Gly Ser Thr Arg Ala Phe Pro Pro His
370 375 380
His Pro Leu Ile Ala Val Asp Tyr Gln Leu Thr Gly Gln Pro Val Leu
385 390 395 400
Ile Gly Gly Thr Met Gly Thr Cys Ser Tyr Val Leu Thr Gly Thr Glu
405 410 415
Gln Gly Met Thr Glu Thr Phe Gly Thr Thr Cys His Gly Ala Gly Arg
420 425 430
Ala Leu Ser Arg Ala Lys Ser Arg Arg Asn Leu Asp Phe Gln Asp Val
435 440 445
Leu Asp Lys Leu Ala Asp Met Gly Ile Ala Ile Arg Val Ala Ser Pro
450 455 460
Lys Leu Val Met Glu Glu Ala Pro Glu Ser Tyr Lys Asn Val Thr Asp
465 470 475 480
Val Val Asn Thr Cys His Asp Ala Gly Ile Ser Lys Lys Ala Ile Lys
485 490 495
Leu Arg Pro Ile Ala Val Ile Lys Gly
500 505
<210>77
<211>1518
<212>DNA
<213>家鼠
<220>
<221>CDS
<222>(1)..(1518)
<400>77
atg agt cgt aac tac aac gat gag cta cag ttc ttg gac aag atc aat 48
Met Ser Arg Asn Tyr Asn Asp Glu Leu Gln Phe Leu Asp Lys Ile Asn
1 5 10 15
aag aac tgc tgg agg atc aag aag ggc ttt gtg ccc aac atg cag gtt 96
Lys Asn Cys Trp Arg Ile Lys Lys Gly Phe Val Pro Asn Met Gln Val
20 25 30
gaa ggg gtg ttt tat gtg aat gac gct ctg gaa aag ctc atg ttt gag 144
Glu Gly Val Phe Tyr Val Asn Asp Ala Leu Glu Lys Leu Met Phe Glu
35 40 45
gag tta cgg aat gcc tgt cga ggt ggt ggt gtt ggt ggc ttc ctg cca 192
Glu Leu Arg Asn Ala Cys Arg Gly Gly Gly Val Gly Gly Phe Leu Pro
50 55 60
gcc atg aag cag att ggc aat gtg gca gcc ctg cct gga ata gtt cat 240
Ala Met Lys Gln Ile Gly Asn Val Ala Ala Leu Pro Gly Ile Val His
65 70 75 80
cgg tct att ggg ctt cct gat gtc cac tca ggc tac ggg ttt gcc ata 288
Arg Ser Ile Gly Leu Pro Asp Val His Ser Gly Tyr Gly Phe Ala Ile
85 90 95
ggg aac atg gct gcc ttt gat atg aat gac cct gag gca gtt gta tcc 336
Gly Asn Met Ala Ala Phe Asp Met Asn Asp Pro Glu Ala Val Val Ser
100 105 110
cca ggt ggt gtc gga ttt gat att aac tgt ggt gtc cgc ttg cta agg 384
Pro Gly Gly Val Gly Phe Asp Ile Asn Cys Gly Val Arg Leu Leu Arg
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acc aat tta gat gag agc gat gta cag cct gtg aag gaa caa ctt gcc 432
Thr Asn Leu Asp Glu Ser Asp Val Gln Pro Val Lys Glu Gln Leu Ala
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caa gct atg ttt gac cac atc cct gtc ggg gtg gga tcg aaa ggt gtc 480
Gln Ala Met Phe Asp His Ile Pro Val Gly Val Gly Ser Lys Gly Val
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att cca atg aat gcc aaa gac ttg gag gag gca ttg gag atg ggt gtg 528
Ile Pro Met Asn Ala Lys Asp Leu Glu Glu Ala Leu Glu Met Gly Val
165 170 175
gac tgg tcc cta aga gaa ggc tat gcc tgg gct gag gac aag gag cac 576
Asp Trp Ser Leu Arg Glu Gly Tyr Ala Trp Ala Glu Asp Lys Glu His
180 185 190
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Cys Glu Glu Tyr Gly Arg Met Leu Gln Ala Asp Pro Asn Lys Val Ser
195 200 205
ccc aga gca aag aaa agg ggc ctt cct cag ttg ggg acc ctg gga gca 672
Pro Arg Ala Lys Lys Arg Gly Leu Pro Gln Leu Gly Thr Leu Gly Ala
210 215 220
ggc aac cat tat gca gag atc cag gtt gta gat gag att ttc aac gag 720
Gly Asn His Tyr Ala Glu Ile Gln Val Val Asp Glu Ile Phe Asn Glu
225 230 235 240
tat gct gcc aag aag atg ggc atc gac cat aag gga cag gtg tgc gtg 768
Tyr Ala Ala Lys Lys Met Gly Ile Asp His Lys Gly Gln Val Cys Val
245 250 255
atg atc cac agc ggg agc aga ggc ttg ggc cat caa gta gct aca gac 816
Met Ile His Ser Gly Ser Arg Gly Leu Gly His Gln Val Ala Thr Asp
260 265 270
gca ctg gta gct atg gag aaa gcc atg aag aga gac aag att ata gtc 864
Ala Leu Val Ala Met Glu Lys Ala Met Lys Arg Asp Lys Ile Ile Val
275 280 285
aat gac cgg cag ctg gcg tgt gct cgg att gca tcc cca gag gga caa 912
Asn Asp Arg Gln Leu Ala Cys Ala Arg Ile Ala Ser Pro Glu Gly Gln
290 295 300
gac tat cta aag gga atg gct gcc gct gga aac tgt gcc tgg gtt aac 960
Asp Tyr Leu Lys Gly Met Ala Ala Ala Gly Asn Cys Ala Trp Val Asn
305 310 315 320
cgc tcg tct atg acc ttc tta acc cgt cag gct ttt gcc aaa gtc ttc 1008
Arg Ser Ser Met Thr Phe Leu Thr Arg Gln Ala Phe Ala Lys Val Phe
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aac aca acc cct gac gac ctg gac ctg cat gtg att tat gat gtt tct 1056
Asn Thr Thr Pro Asp Asp Leu Asp Leu His Val Ile Tyr Asp Val Ser
340 345 350
cac aac atc gcc aaa gtg gag cag cac gtg gta gac gga aag gag cgg 1104
His Asn Ile Ala Lys Val Glu Gln His Val Val Asp Gly Lys Glu Arg
355 360 365
acg ctg ttg gtg cac agg aaa ggg tcc acc cgc gct ttc cct cct cac 1152
Thr Leu Leu Val His Arg Lys Gly Ser Thr Arg Ala Phe Pro Pro His
370 375 380
cat ccc ctc att gct gtt gat tac cag ctc act gga caa cca gtg ctt 1200
His Pro Leu Ile Ala Val Asp Tyr Gln Leu Thr Gly Gln Pro Val Leu
385 390 395 400
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Ile Gly Gly Thr Met Gly Thr Cys Ser Tyr Val Leu Thr Gly Thr Glu
405 410 415
caa ggc atg act gag acc ttt gga aca acc tgt cat gga gcg ggc cgt 1296
Gln Gly Met Thr Glu Thr Phe Gly Thr Thr Cys His Gly Ala Gly Arg
420 425 430
gct ttg tcc aga gca aaa tca cgt cgt aat tta gat ttc caa gat gtc 1344
Ala Leu Ser Arg Ala Lys Ser Arg Arg Asn Leu Asp Phe Gln Asp Val
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tta gac aag ctg gca gac atg gga atc gcc atc cgg gtt gcg tcc ccc 1392
Leu Asp Lys Leu Ala Asp Met Gly Ile Ala Ile Arg Val Ala Ser Pro
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aag ctg gtt atg gaa gag gct cca gaa tca tat aag aat gtg aca gac 1440
Lys Leu Val Met Glu Glu Ala Pro Glu Ser Tyr Lys Asn Val Thr Asp
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gtc gtg aac act tgc cat gat gct ggg atc agc aag aag gcc att aaa 1488
Val Val Asn Thr Cys His Asp Ala Gly Ile Ser Lys Lys Ala Ile Lys
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ctg aga cca att gct gtt att aaa gga tag 1518
Leu Arg Pro Ile Ala Val Ile Lys Gly
500 505
<210>78
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<212>PRT
<213>家鼠
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Met Ser Arg Asn Tyr Asn Asp Glu Leu Gln Phe Leu Asp Lys Ile Asn
1 5 10 15
Lys Asn Cys Trp Arg Ile Lys Lys Gly Phe Val Pro Asn Met Gln Val
20 25 30
Glu Gly Val Phe Tyr Val Asn Asp Ala Leu Glu Lys Leu Met Phe Glu
35 40 45
Glu Leu Arg Asn Ala Cys Arg Gly Gly Gly Val Gly Gly Phe Leu Pro
50 55 60
Ala Met Lys Gln Ile Gly Asn Val Ala Ala Leu Pro Gly Ile Val His
65 70 75 80
Arg Ser Ile Gly Leu Pro Asp Val His Ser Gly Tyr Gly Phe Ala Ile
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Gly Asn Met Ala Ala Phe Asp Met Asn Asp Pro Glu Ala Val Val Ser
100 105 110
Pro Gly Gly Val Gly Phe Asp Ile Asn Cys Gly Val Arg Leu Leu Arg
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Thr Asn Leu Asp Glu Ser Asp Val Gln Pro Val Lys Glu Gln Leu Ala
130 135 140
Gln Ala Met Phe Asp His Ile Pro Val Gly Val Gly Ser Lys Gly Val
145 150 155 160
Ile Pro Met Asn Ala Lys Asp Leu Glu Glu Ala Leu Glu Met Gly Val
165 170 175
Asp Trp Ser Leu Arg Glu Gly Tyr Ala Trp Ala Glu Asp Lys Glu His
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Cys Glu Glu Tyr Gly Arg Met Leu Gln Ala Asp Pro Asn Lys Val Ser
195 200 205
Pro Arg Ala Lys Lys Arg Gly Leu Pro Gln Leu Gly Thr Leu Gly Ala
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Gly Asn His Tyr Ala Glu Ile Gln Val Val Asp Glu Ile Phe Asn Glu
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Tyr Ala Ala Lys Lys Met Gly Ile Asp His Lys Gly Gln Val Cys Val
245 250 255
Met Ile His Ser Gly Ser Arg Gly Leu Gly His Gln Val Ala Thr Asp
260 265 270
Ala Leu Val Ala Met Glu Lys Ala Met Lys Arg Asp Lys Ile Ile Val
275 280 285
Asn Asp Arg Gln Leu Ala Cys Ala Arg Ile Ala Ser Pro Glu Gly Gln
290 295 300
Asp Tyr Leu Lys Gly Met Ala Ala Ala Gly Asn Cys Ala Trp Val Asn
305 310 315 320
Arg Ser Ser Met Thr Phe Leu Thr Arg Gln Ala Phe Ala Lys Val Phe
325 330 335
Asn Thr Thr Pro Asp Asp Leu Asp Leu His Val Ile Tyr Asp Val Ser
340 345 350
His Asn Ile Ala Lys Val Glu Gln His Val Val Asp Gly Lys Glu Arg
355 360 365
Thr Leu Leu Val His Arg Lys Gly Ser Thr Arg Ala Phe Pro Pro His
370 375 380
His Pro Leu Ile Ala Val Asp Tyr Gln Leu Thr Gly Gln Pro Val Leu
385 390 395 400
Ile Gly Gly Thr Met Gly Thr Cys Ser Tyr Val Leu Thr Gly Thr Glu
405 410 415
Gln Gly Met Thr Glu Thr Phe Gly Thr Thr Cys His Gly Ala Gly Arg
420 425 430
Ala Leu Ser Arg Ala Lys Ser Arg Arg Asn Leu Asp Phe Gln Asp Val
435 440 445
Leu Asp Lys Leu Ala Asp Met Gly Ile AIa Ile Arg Val Ala Ser Pro
450 455 460
Lys Leu Val Met Glu Glu Ala Pro Glu Ser Tyr Lys Asn Val Thr Asp
465 470 475 480
Val Val Asn Thr Cys His Asp Ala Gly Ile Ser Lys Lys Ala Ile Lys
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Leu Arg Pro Ile Ala Val Ile Lys Gly
500 505
Claims (30)
1.一种检测第一蛋白改变的方法，其包括筛选至少一个第二蛋白的错误折叠或聚集，其中第一蛋白选自泛素-蛋白酶体降解系统蛋白、自噬蛋白、分子伴侣、转录因子、膜泡转运蛋白、Mn2+/Fe2+转运子、HSPCI 17蛋白、乙酰胆碱受体亚单位、DJ-I蛋白和PINK-I蛋白。
2.如权利要求1所述的方法，其中所述的改变包括第一蛋白表达的升高或降低。
3.如权利要求1所述的方法，其中所述的改变包括第一蛋白的突变。
4.一种诊断神经疾病的方法，其包括检测个体来源的组织样品中蛋白的改变，所述蛋白选自泛素-蛋白酶体降解系统蛋白、自噬蛋白、分子伴侣、转录因子、膜泡转运蛋白、Mn2+/Fe2+转运子、HSPCI 17蛋白、乙酰胆碱受体亚单位、DJ-I蛋白和PINK-I蛋白，其中的改变显示了神经疾病的易感性或发生。
5.如权利要求4所述的方法，其进一步包括在体内或体外模型中测定蛋白错误折叠或聚集的量。
6.如权利要求4所述的方法，其中所述蛋白通过使用特异于野生型的该蛋白或改变形式的该蛋白的抗体来检测。
7.如权利要求4所述的方法，其中所述蛋白通过特异于野生型的该蛋白或改变形式的该蛋白相应的多核苷酸或多肽的可探测标签来检测。
8.如权利要求4所述的方法，其中所述蛋白使用微阵列检测，该微阵列包括特异于编码野生型的该蛋白或改变形式的该蛋白的多核苷酸的探针。
9.一种筛选治疗神经疾病的化合物的方法，其包括将靶化合物与选自下述的蛋白相接触：泛素-蛋白酶体降解系统蛋白、自噬蛋白、分子伴侣、转录因子、膜泡转运蛋白、Mn2+/Fe2+转运子、HSPCI 17蛋白、乙酰胆碱受体亚单位、DJ-I蛋白和PINK-I蛋白，并且测定缺少此化合物时该蛋白的活性变化。
10.如权利要求9所述的方法，其中所述的活性变化包括所述蛋白表达的升高或降低。
11.如权利要求9所述的方法，其进一步包括检测至少一个第二蛋白的错误折叠或聚集。
12.如权利要求9所述的方法，其进一步包括将所述化合物施用至神经疾病动物模型以降低至少一个第二蛋白的错误折叠和聚集。
13.如权利要求9所述的方法，其进一步包括将所述化合物施用至神经动物模型，以在此动物模型中提供神经保护。
14.如权利要求12所述的方法，其中所述化合物选自拓扑异构酶II抑制剂、细菌转肽酶抑制剂、钙通道阻遏物、环氧合酶抑制剂、叶酸合成抑制剂和钠通道阻遏物。
15.如权利要求13所述的方法，其中所述化合物选自叶酸合成抑制剂、细菌转肽酶抑制剂、环氧合酶抑制剂和钠通道阻遏物。
16.选自如下的蛋白在制备治疗神经疾病的药物中的应用：泛素-蛋白酶体降解系统蛋白、自噬蛋白、分子伴侣、转录因子、膜泡转运蛋白、Mn2+/Fe2+转运子、HSPCI 17蛋白、乙酰胆碱受体亚单位、DJ-I蛋白和PINK-I蛋白，其中所述药物包括治疗所述神经疾病症状的有效量的该蛋白。
17.一种对需要治疗的个体进行治疗神经疾病的方法，其包括改变第一蛋白的活性，所述第一蛋白选自泛素-蛋白酶体降解系统蛋白、自噬蛋白、分子伴侣、转录因子、膜泡转运蛋白、Mn2+/Fe2+转运子、HSPCI 17蛋白、乙酰胆碱受体亚单位、DJ-I蛋白和PINK-I蛋白。
18.如权利要求17所述的方法，其中所述的第一蛋白的活性改变是通过将表达第二蛋白的载体施用至需要治疗的个体而实现的，所述的第二蛋白选自泛素-蛋白酶体降解系统蛋白、自噬蛋白、分子伴侣、转录因子、膜泡转运蛋白、Mn2+/Fe2+转运子、HSPCI 17蛋白、乙酰胆碱受体亚单位、DJ-I蛋白和PINK-I蛋白。
19.如权利要求17所述的方法，其中所述蛋白保护神经元免遭功能紊乱、变性或死亡。
20.如权利要求17所述的方法，其中所述第一蛋白的活性是通过给予化合物来改变第一蛋白在无该化合物时的活性而改变的。
21.如权利要求17所述的方法，其中所述神经疾病选自肌萎缩性侧索硬化症、阿耳茨海默氏病、帕金森氏病、朊病毒病、多谷氨酰胺扩增病、脊髓-小脑共济失调、脊髓性和延髓性肌肉萎缩、海绵状脑病、tau蛋白病、亨廷顿舞蹈病或者肌张力障碍。
22.如权利要求17所述的方法，其中在易患所述神经疾病的个体出现症状前改变第一蛋白的活性。
23.如权利要求20所述的方法，其中所述化合物选自拓扑异构酶II抑制剂、细菌转肽酶抑制剂、钙通道阻遏物、环氧合酶抑制剂、叶酸合成抑制剂和钠通道阻遏物。
24.如权利要求20所述的方法，其中所述化合物以存在于药物学上可接受的载体中的形式给药。
25.如权利要求20所述的方法，其中所述化合物通过吸入、经皮、口服、直肠、经粘膜、肠内或肠胃外的途径给药。
26.如权利要求20所述的方法，其中在易患所述神经疾病的个体出现症状前给予所述化合物。
27.一种转基因动物，其包括与野生型动物相比具有改变活性的以下的蛋白：泛素-蛋白酶体降解系统蛋白、自噬蛋白、分子伴侣、转录因子、膜泡转运蛋白、Mn2+/Fe2+转运子、HSPCI 17蛋白、乙酰胆碱受体亚单位、DJ-I蛋白和PINK-I蛋白。
28.如权利要求27所述的转基因动物，其中所述的改变活性包括所述蛋白表达的升高或降低。
29.如权利要求27所述的转基因动物，其中改变活性包括所述蛋白序列的突变。
30.一种使用权利要求1、4、9或17任意一项所述方法的试剂盒。
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US65633405P | 2005-02-25 | 2005-02-25 | |
| US60/656,334 | 2005-02-25 | ||
| US60/681,890 | 2005-05-17 | ||
| US60/738,761 | 2005-11-21 | ||
| US60/749,910 | 2005-12-12 |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107261133A (zh) * | 2008-02-22 | 2017-10-20 | 阿费里斯股份公司 | 用于治疗神经退行性变疾病的α‑突出核蛋白和其疫苗的模拟表位 |
| CN109152350A (zh) * | 2016-03-01 | 2019-01-04 | Smc全球资产株式会社 | 呈现出由蛋白质凝聚引起的退行性症状的非人动物 |
| CN111454911A (zh) * | 2020-04-01 | 2020-07-28 | 苏州系统医学研究所 | 靶向erad的化合物筛选系统及其应用 |
| CN111537745A (zh) * | 2020-05-27 | 2020-08-14 | 南京大学 | 热休克蛋白90kDaαB1在检测纳米颗粒导致蛋白变性程度中的应用 |
-
2006
- 2006-02-27 CN CNA200680006130XA patent/CN101142482A/zh active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107261133A (zh) * | 2008-02-22 | 2017-10-20 | 阿费里斯股份公司 | 用于治疗神经退行性变疾病的α‑突出核蛋白和其疫苗的模拟表位 |
| US11534484B2 (en) | 2008-02-22 | 2022-12-27 | Ac Immune Sa | Mimotopes of alpha-synuclein and vaccines thereof for the treatment of synucleinopathy |
| CN109152350A (zh) * | 2016-03-01 | 2019-01-04 | Smc全球资产株式会社 | 呈现出由蛋白质凝聚引起的退行性症状的非人动物 |
| CN111454911A (zh) * | 2020-04-01 | 2020-07-28 | 苏州系统医学研究所 | 靶向erad的化合物筛选系统及其应用 |
| CN111537745A (zh) * | 2020-05-27 | 2020-08-14 | 南京大学 | 热休克蛋白90kDaαB1在检测纳米颗粒导致蛋白变性程度中的应用 |
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