CN1432062A - 新的蛋白质及编码该蛋白质的基因 - Google Patents
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Abstract
本发明提供了新的蛋白质及其编码基因。在肾脏内特异性表达的、有对机械刺激应答而非选择性地将阳离子摄入细胞内的功能的衍生自小鼠或人的新的应答机械刺激的通道蛋白。编码该蛋白质的DNA。用该蛋白质筛选促进或阻滞阳离子通道活性的物质的方法。针对该蛋白质的抗体。它可用作高血压、糖尿病等基于阳离子通道异常的疾病的诊断药或治疗药,或者可用作用来寻找预防和/或治疗这些疾病的药物的工具。
Description
技术领域
本发明涉及在肾脏内特异性表达的衍生自小鼠或人的新的动力敏感通道蛋白(机械刺激应答通道蛋白)(SAC1(小鼠)和hSAC(人),编码这些蛋白质的DNA,用该蛋白质来筛选促进或阻滞阳离子通道活性的物质的方法,以及针对该蛋白质的抗体。
本发明的蛋白质、DNA以及针对该蛋白质的抗体可用作高血压、糖尿病等基于阳离子通道异常的疾病的诊断药或治疗药,或者可用作用来寻找预防和/或治疗这些疾病的药物的工具。另外,在本发明中,SAC1和hSAC等动力敏感通道蛋白统称为SAC。
背景技术
离子通道是以脂质双层为基本构造的跨生物膜存在的膜内在性蛋白质,其内部有孔结构。离子通道根据其电生理学性质、即门控、电导和离子选择性等分类。离子通道分子具有多个构象,在某一状态(开状态)下允许离子通过,而在其它状态(闭状态)下则不允许。这种构象变化称为“门的开关(门控;gating)”。控制这种门控的因素已知有三种:膜电位、小分子(配体)的结合和膜牵张。
电位依赖性通道的例子有Na+通道、Ca2+通道、K+通道等,在这些通道的分子结构中有电荷集合的部位或是电位传感器。认为它由于膜两侧的电位差而受力移动从而引起构象变化。配体敏感型通道是通过与来自细胞外的特异性配体(激动剂)结合而活化的通道,称为受体内藏通道。与此相对,有通过与细胞内的第二信使等小分子结合来控制开闭的通道。细胞膜内存在的IP3(肌醇三磷酸)受体(与来自胞质侧的IP3结合后打开的Ca2+通道)是一个例子。动力敏感通道是通过膜牵张来控制门开闭的离子通道,由于很多是通过牵张来打开,因此称为“牵张敏感性”通道。认为该通道与渗透压调节和细胞体积调节有关。这种通道中当然存在肌梭等牵张感受器。目前已经在多种细胞中发现这种通道(Morris C.E.,J.Membrane Biol.,113,93-107(1990);Bear,C.E.,Am.J.Physiol.,258,C421-8(1990);Cemerik,D. & Sackin,H.,Am.J.Physiol.,264,F697-714(1993);Lansman,J.B.,等人,Nature,325,811-3(1987);Sackin,H.,Am.J.Physiol.,253,F1253-62(1987))。
另外,已经表明,编码具有4个跨膜部位的TWIK1(弱内向整流K+通道中的连串P结构域)有关的TASK(TWIK-1相关的酸敏感型K+通道)的哺乳动物K+通道具有靠机械刺激来开闭的性质(Duprat,F.,等人.,(1997)EMBO J.,16,5464-71,Patel,A.J.,等人.,(1998)EMBO J.17,4283-90)。
本发明者根据这样一个假定,即对物理因素热敏感的香兰素样(Vanilloid)受体是机械刺激应答通道,进行了基因克隆。结果报道了与香兰素样受体(Caterina,M.J.,等人.,(1997)Nature,389,816-24)相似的具有锚蛋白重复序列和6个跨膜部位并且通过牵张来抑制的非选择性阳离子通道(SIC)的编码cDNA(Suzuki,M.,等人.,(1999)J.Biol.Chem.274,6330-5)。由于机械刺激应答通道能将机械性刺激转变成Ca2+流入,所以通过牵张来活化(stretch-activated;SA)的非选择性阳离子通道很重要。
发明揭示
鉴于上述情况,本发明者深入研究了新的机械应答通道蛋白质,结果发现了肾脏特异性表达的、具有对机械刺激应答从而非选择性地将阳离子摄入细胞内的功能的蛋白质,即,新的机械刺激应答通道蛋白质。因此,本发明的课题是提供从小鼠或人衍生获得的肾脏特异性表达的、具有对机械刺激应答从而非选择性地将阳离子摄入细胞内的功能的新的机械刺激应答通道蛋白质(SAC1(小鼠)(牵张活化通道蛋白1)和hSAC(人)(人牵张活化通道蛋白)),编码该蛋白质的DNA,使用该蛋白质来筛选促进或抑制阳离子通道活性的物质的方法,以及针对该蛋白质的抗体。
本发明涉及一种从小鼠或人衍生获得的、肾脏特异性表达的、具有对机械刺激应答从而非选择性地将阳离子摄入细胞内的功能的新的机械刺激应答通道蛋白质(SAC1(小鼠)和hSAC(人))。另外,本发明还涉及编码该蛋白质的DNA。另外,本发明还涉及使用该蛋白质来筛选促进或抑制阳离子通道活性的物质的方法。另外,本发明还涉及针对该蛋白质的抗体。所述蛋白质、DNA以及针对该蛋白质的抗体可用作高血压、糖尿病等基于阳离子通道异常的疾病的诊断药或治疗药,或者可用作用来寻找预防和/或治疗这些疾病的药物的工具。
为了进行新膜通道的分离、鉴定和功能分析,需要分子生物学技术、细胞生物学技术以及电生理学技术等先进的技术。因此,本发明者使用这些技术从小鼠肾脏中分离出SA阳离子通道(SAC1)的cDNA,确定了其氨基酸序列。它属于香兰素样受体超家族,局部存在于肾脏的肾小管中。该SAC1在哺乳动物细胞系中表达。另外,用衍生自小鼠的SAC1基因获得了人对应的通道基因。
电生理学分析的结果是,通过机械刺激表达SAC1的转化细胞,细胞内的游离钙增加。另外,它是通过负压活化的单一通道,被Gd3+阻滞,对阳离子的通过是非选择性的,且SAC1中的离子透过性Na+大于K+。细胞的逆转电位通过细胞膨胀向正电位侧偏移。另外,由于当使缺失突变表达时通道对牵张没有应答性,因此暗示SAC1成为SA通道。
如上所述,本发明涉及一种从小鼠或人衍生获得的、肾脏特异性表达的、具有对机械刺激应答从而非选择性地将阳离子摄入细胞内的功能的新的机械刺激应答通道蛋白质(SAC1(小鼠)和hSAC(人))以及编码该蛋白质的DNA。本发明的蛋白质可如下所示获得。即,构建小鼠肾脏cDNA库,采用适当的引物通过PCR扩增得到SAC1cDNA。并且,以该SAC1 cDNA作为探针通过对人肾脏cDNA库进行克隆,得到hSACcDNA。衍生自小鼠的SAC1是由871个氨基酸残基组成的蛋白质,而衍生自人的hSAC也是由871个氨基酸残基组成的蛋白质。它们的氨基酸序列表现出94.4%的同源性。认为这种显著的同源性表示SAC1在哺乳动物细胞中有共同的结构和功能。编码hSAC的DNA长约18kb,由14个外显子构成,存在于染色体12q24.1中。
将所得小鼠或人的SAC基因导入合适的载体中,用该载体转化宿主,就能得到小鼠或人的SAC蛋白质。作为宿主细胞可列举细菌、酵母或动物细胞等。特别是动物细胞,宜采用HeLa细胞、中国仓鼠卵巢(CHO)细胞或COS-7细胞等。另外,作为细胞系表达质粒的控制作用,可使用病毒的多形瘤、腺病毒、巨细胞病毒、猿病毒40的启动子。特别是作为动物细胞表达体系中利用性高的质粒,宜为pCMV(Thomsen,等人.,PNAS,(1984)81,659)。所得蛋白质是对机械刺激有应答的膜结合蛋白,可用作高血压或糖尿病等基于阳离子通道异常的疾病的诊断药或治疗药,或者可用作用来寻找预防和/或治疗这些疾病的药物的工具。
另外,本发明的蛋白质或其片段可用于缺损hSAC的DNA的杂交诊断,hSAC突变体可用于高血压病和糖尿病的研究。另外,也可用公知的技术不难通过SAC的DNA及其突变体的5′和3′端与其它蛋白质或合成多肽的编码核苷酸序列结合来获得融合蛋白质。例如,可将融合蛋白制成前体蛋白,在体外和体内切割时发挥作用。除了其本来的功能外,还可以有指向目标组织等的靶向性。
另外,用表达的蛋白质、其突变体及其片段免疫动物,可得到多克隆抗体。另外,将受免疫动物的淋巴细胞与骨髓瘤细胞融合,用融合而成的杂交瘤细胞可制得单克隆抗体。
另外,本发明的蛋白质或其突变体和类似物可用来寻找作为通道蛋白质相关疾病的诊断药或治疗药等的对SAC有激动作用和拮抗作用的物质。另外,由于得到了SAC的DNA序列信息,因此制备部分DNA或RNA序列很容易。由于这些部分DNA具有与合适选择的基因杂交的能力,因此可用作核酸探针。这些探针能有效地检测各种组织中的cDNA序列。利用用SAC制得的探针能从各种生物及其组织中得到杂交核酸。所得核酸包括编码与SAC相同的同种型的核酸或是编码显示新特性的蛋白质的核酸。另外,制得的探针可用于疾病的基因诊断。通过鉴别与该探针杂交的患者的核苷酸序列,可能会检测出疾病基因。另外,还包括用于治本疗法的基因治疗药。SAC、其突变体及其衍生物的核苷酸序列可通过参入质粒或干细胞中来给药,作为基因治疗药使用。
本发明的蛋白质以及针对该蛋白质的抗体可对人和灵长动物安全地给药。本发明的蛋白质可制成制剂进行经口或非经口的给药。药物组合物的形式可列举注射用组合物、灌输用组合物、栓剂、经鼻剂、舌下剂、经皮吸收剂等。这些制剂可根据公知的制剂学方法来配制,通过使用药理学上容许的载体、赋形剂、稳定剂、着色剂、表面活性剂和/或其它添加剂等,制成目标制剂。在注射用组合物场合,宜将药理学有效量的本发明蛋白质与制药学上容许的赋形剂/活化剂(如氨基酸、糖类、纤维素衍生物和其它有机/无机化合物等)混合。另外,在用本发明抗体和这些赋形剂/活化剂来配制注射剂的场合,可根据需要通过常规方法添加pH调节剂、缓冲剂、稳定剂、增溶剂等,制成各种注射剂。
另外,本发明的DNA可单独或通过包封在脂质体内或插入逆转录病毒或腺病毒等基因治疗用载体中用于基因治疗。
附图简单说明
图1(a)显示了用全长cDNA进行的SAC1 mRNA表达的Northern印迹分析的结果。各泳道加入从小鼠组织制得的总RNA(2微克)。
图1(b)显示了用肾脏组织的免疫染色结果。染色部分用白色表示。
图2显示了对SAC1表达细胞(GFP阳性)对触摸应力的影响的调查结果。
图中,○、▲、●分别表示380nm下的荧光强度、荧光强度比(360nm/380nm)和360nm下的荧光强度。
图3显示了对于SAC单一通道牵张的应答结果。
(A)显示了分阶段施加负压时的SAC1通道的典型结果。
(B)显示了缓慢施加负压时的结果。
(C)显示了在添加和不添加GdCl3时向SAC1施加的压力与Po之间的关系。
图中,○和△分别表示对照(不加GdCl3时的压力)和添加0.5M GdCl3时的压力。
实施发明的最佳方式
实施例
本发明根据下面的实施例作详细的说明,但是,这些只是为了举例目的,本发明并不局限于这些实施例。
实施例1
编码SAC1的cDNA的分离
RNA通过硫氰酸胍方法用Trizol(Gibco-BRL)分离。mRNA用polyA柱(Pharmacia)纯化。用Marathon cDNA构建试剂盒(Clonetech Co.)制备小鼠肾脏cDNA库。cDNA用引物系列1(AA13f2(序列表SEQ ID NO:5)和mA13end1(SEQ ID NO:6)以ExTaq聚合酶(宝酒造社)进行PCR扩增(94℃30秒,70℃4分钟作为1轮,进行30轮)。合成嵌套引物(AAl3r2(SEQ ID NO:7)),用5′RACE法测定5′末端。用引物系列2(A13st1(SEQID NO:8)和AA13r1(SEQ ID NO:9))以及ExTaq聚合酶(宝酒造社)在相同条件下进行PCR扩增。使用2种引物系列PCR扩增得到的片段,用引物系列(A13st1和mA13end1)PCR扩增含有全长的区域。再次从cDNA库中克隆约3.2kb的SAC1 cDNA。将克隆的cDNA与TA克隆载体(TOPO-XL;InVitrogen)连接,将其BamHI-HindIII片段连接入哺乳动物细胞表达载体(pCMV-SPORT;Gibco-BRL)。用热测序酶染色终止循环测序预混物(Thermo Sequenase dye terminator cycle sequencing premix)在自动化测序仪(373-S型;Applied Bioinstruments Inc.)中进行测序。SAC1 cDNA是编码871个氨基酸的2616个核苷酸。其序列在序列表中是SEQ ID NO:1(氨基酸序列)和SEQ IDNO:2(核苷酸序列)。插入了SAC1 cDNA的质粒命名为pmSAC1 TOPO,最初于1999年11月30日保藏于国立生命科学和人体技术研究所(日本茨城县Tsukuba市东一区1番3号(邮编305-8566))。随后于2000年11月1日根据布达佩斯条约请求转移保藏,保藏号为FERM BP-7345。
然后,用32P标记过的SAC1 cDNA作为探针通过Northern杂交(65℃)确认SAC1在各组织中的表达。结果确认约3kb的SAC1 mRNA仅在肾脏中表达(图1(a))。
另外,为了分离编码衍生自人的SAC(hSAC)的cDNA,用32P标记过的SAC1cDNA作为探针来筛选人肾脏cDNA库。将所得克隆分别亚克隆到载体M13mp1、M13mp19(宝酒造社)和pGEM3Z(Promega Co.)中,用上述同样方法测定核苷酸序列。序列用序列表中SEQ ID NO:3(氨基酸序列)和SEQ ID NO:4(核苷酸序列)表示。
实施例2
抗体的制备和免疫染色
制备针对和聚乙二醇结合的SAC1蛋白质C端部(844-853)的特异性肽(下文称为“C端肽”)(序列表中SEQ ID NO:10)的抗体。小鼠SAC1蛋白质C端肽与聚乙二醇(PEG)的结合根据Maeda等人的方法(Biochem.Biophys.Res.Comm.(1998)248,485-489)进行。即,在溶解于二氯甲烷的氧化PEG(和光纯药社)中添加1当量二环己基碳二亚胺,在0℃下搅拌后,添加10当量的乙二胺搅拌过夜。从滤液中蒸发除去溶剂,将所得产物溶解在50%乙酸中。用Sephadex G-25柱纯化氨基酸型PEG(aaPEG),N末端氨基Fmoc化,制得Fmoc-aaPEG。用二异丙基碳二亚胺/1-羟基苯并三唑法(Konig和Geiger,Chem.Ber.(1970)103,788-798,2024-2033),将Fmoc-aaPEG、然后是Boc-PLD(Pmc)NLGNPNC-OH连接到Rink树脂(300毫克;渡边化学社)上。除去Fmoc后,树脂在三氟乙酸/茴香硫醚/苯甲醚/乙二硫醇(94/2/2/2)中处理3小时,切除C端肽aaPEG。在滤液中添加乙醚,用反相HPLC纯化沉淀的肽粗产物,得到43毫克C端肽-aaPEG。
将在Freund完全佐剂中乳化的抗原(C端肽-aaPEG)1毫克肌内注入2只NZW家兔进行免疫,然后每2周用经Freund不完全佐剂乳化的同样量的抗原同样免疫。给药后4-8周后,用ELISA法测定血清的抗体滴度。分离出滴度比对照血清高10000倍的血清。用Protein A柱(Pharmacia Co.)从血清中纯化出抗体,然后用Proton试剂盒(Multiple Peptide System Co.)进行亲和纯化。用500倍稀释的抗体对新鲜肾脏切片染色后,用FITC标记的抗家兔IgG抗体(DAKO Co.)检测蛋白。结果发现,肾小管基底膜被染色,表明该部位局部存在SAC1蛋白(见图1(b))。
实施例3
cDNA的表达
将表达绿色荧光蛋白的质粒(pEGFP-N1;Clonetech Co.)用作转染标记物。为了进行瞬时表达,使CHO细胞在添加了10%胎牛血清、100U/ml青霉素和100微克/毫升链霉素的HamF-12培养基(Gibco-BRL)中培养。在转化前一日,将105个CHO细胞添加到35mm平皿中,平皿内放置了涂布有大鼠尾部胶原的条状盖板。第二天,每次转染时将pCMV-SPORT(Gibco-BRL)中的SAC1质粒(1微克)和pEGFP-N1(1微克)添加到在室温下培育5分钟的FuGENE6(Roche,3微升)和无血清培养基(97微升)的混合液中。室温下培育15分钟后,将该混合液加入含有3毫升血清培养基的平皿中。用条状盖板上生长的细胞作为膜片钳样品。增殖和转染中使用含10%FCS的培养基。电生理学实验在24小时后开始,荧光测定在转染后48小时进行。
实施例4
SAC1表达细胞中的荧光测定
在实验开始前2-3小时,用无血清培养基溶解的10μM fura-2AM(Dojin Co.)培育转化的细胞。480nm的GFP荧光和360/380nm的fura-2荧光用二向色性Olympus系统反射镜(Merlin Co.)以手工交换来视觉化。每2秒得到480nm的荧光和360/380nm下荧光的图象。为了进行分析,算出目标区域的荧光强度。将细胞浸在34℃125mMNaCl、5mM KCl、1.2mM MgSO4、1mM Na2HPO4、1mM CaCl2、3mM HEPES(pH7.4)溶液中。为了产生直接对细胞的机械应力,用电控制的显微操作仪(5170型;EppendorfCo.)使细胞与玻璃移液管圆形前端接触。图2和表1显示了通过用玻璃移液管给明亮的细胞(GFP阳性)机械刺激的结果。与对照细胞相比,确认SAC1表达细胞fura-2荧光比发生变化,因此暗示本发明蛋白质具有通道蛋白质的功能,明显使[Ca2+]i(细胞内钙离子浓度)发生变动。表1
未添加Gd3+ | 添加Gd3+ | |
对照细胞 | 4.5±3.8(8) | |
SAC1表达细胞 | 12.8±1.4**(8) | 4.8±1.4(10) |
(括号内的数字表示实验次数,**表示与对照相比在1%有显著性,*表示与未添加Gd3+时相比在5%有显著性)。
实施例5
SAC1表达细胞的信号通道分析
根据以前的报道(Suzuki,M.,Sato.J.,Kutsuwada,K.,Ooki,G.和Imai,M.(1999)J.Biol.Chem.274,6330-5)进行膜片钳记录。在490nm下进行荧光测定(CAM2000系统;Jusco Co.,Ltd.),检出GFP阳性细胞。在1毫升/毫升的回流溶液流速下将细胞固定在架上。固定前,为了控制温度,用DC电源(菊水电子工业社;LPD型)将溶液加温至34℃。用140mM NaCl、5mM KCl、1.2mM MgSO4、1mM Na2HPO4、1mM CaCl2、3mMHEPES的溶液作为浸渍液。在单通道分析中,用EPC-7膜片钳放大器(List-ElectronicCo.,Ltd.)记录电流,以10KHz保存在DAT记录仪(DAT-200;Sony Corp)中。施加5KHz滤波器进行分析。为了分析打开几率,用Fetchex(Software Axon,6.0版)对记录取样。数据用Igor 2.01版和Patch Analysist 1.21版进行解析。在2KHz下使用数字滤波器,通过电流分布分析来计算打开几率。为了计算GdCl3添加时的打开几率,在未加试剂时设定单通道振幅,从10秒的记录测定平均打开几率Po。用压力计调节移液管压力,用手工使负压变化。为了测定通道打开,用150mM NaCl溶液,通过细胞附着移液管施加负压。结果,表达细胞上半数以上的膜片显示出负压引起的通道活性。如图3A所示,在30mmHg负压下,SAC1通道快速打开。打开几率突然达到完全打开的状态,为了确认这一现象,缓慢进行抽吸(图3B),就象打开存在阈值一样,通道突然打开。该阈值是恒定的(33±2.3mmHg),可再现的。使用各种溶液(氯化钠、葡糖酸钠或氯化钾)以移液管测定电流-电压关系,没有观察到有很大的偏差。单通道电导用细胞附着模型下的电导梯度来测定。即使用葡糖酸钠或氯化钾代替氯化钠,这些参数也几乎没有受影响,因此表明该通道对于阳离子是非选择性的。对压力有不同敏感性的个别通道中的全有或全无(all-or-none)打开的积累显示出伴随牵张有S形打开应答。然而,压力P。不适合Bolzmann函数。当移液管中加入0.5μM GdCl3时,应答不受影响,因此表明该蛋白具有机械刺激应答通道蛋白的功能(图3C)。
产业上的利用可能性
本发明提供了在肾脏内特异性表达的衍生自小鼠或人的新的动力敏感通道蛋白(机械刺激应答通道蛋白)(SAC1小鼠)和hSAC(人),该蛋白具有对机械刺激应答来非选择性地将阳离子摄入细胞内的功能,本发明还提供了编码这些蛋白质的DNA,用该蛋白质来筛选促进或阻滞阳离子通道活性的物质的方法,以及针对该蛋白质的抗体。该蛋白质、DNA以及针对该蛋白质的抗体可用作高血压、糖尿病等基于阳离子通道异常的疾病的诊断药或治疗药,或者可用作用来寻找预防和/或治疗这些疾病的药物的工具。
保藏的生物材料的信息
A.保藏该生物材料的保藏机构的名称和地址
名称:国立生命科学和人体技术研究所
地址:日本茨城县Tsukuba市东一区1番3号(邮编305-3566)
B.交A的机构保藏的日期1999年11月30日(原保藏日)
C.A的保藏机构给予的保藏号FERM BP-7345
序列表<110>雪印乳业株式会社<120>新的蛋白质及编码该蛋白质的基因<130>SNOW-135<150>JP 48727-2000<151>2000-2-25<160>10<170>PatentIn Ver.2.1<210>1<211>871<212>PRT<213>小鼠<400>1Met Ala Asp Pro Gly Asp Gly Pro Arg Ala Ala Pro Gly Glu Val Ala1 5 10 15Glu Pro Pro Gly Asp Glu Ser Gly Thr Ser Gly Gly Glu Ala Phe Pro
20 25 30Leu Ser Ser Leu Ala Asn Leu Phe Glu Gly Glu Glu Gly Ser Ser Ser
35 40 45Leu Ser Pro Val Asp Ala Ser Arg Pro Ala Gly Pro Gly Asp Gly Arg
50 55 60Pro Asn Leu Arg Met Lys Phe Gln Gly Ala Phe Arg Lys Gly Val Pro65 70 75 80Asn Pro Ile Asp Leu Leu Glu Ser Thr Leu Tyr Glu Ser Ser Val Val
85 90 95Pro Gly Pro Lys Lys Ala Pro Met Asp Ser Leu Phe Asp Tyr Gly Thr
100 105 110Tyr Arg His His Pro Ser Asp Asn Lys Arg Trp Arg Arg Lys Val Val
115 120 125Glu Lys Gln Pro Gln Ser Pro Lys Thr Pro Ala Pro Gln Pro Pro Pro
130 135 140Ile Leu Lys Val Phe Asn Arg Pro Ile Leu Phe Asp Ile Val Ser Arg145 150 155 160Gly Ser Thr Ala Asp Leu Asp Gly Leu Leu Ser Phe Leu Leu Thr His
165 170 175Lys Lys Arg Leu Thr Asp Glu Glu Phe Arg Glu Pro Ser Thr Gly Lys
180 185 190Thr Cys Leu Pro Lys Ala Leu Leu Asn Leu Ser Asn Gly Arg Asn Asp
195 200 205Thr Leu Gln Val Leu Leu Asp Ile Ala Glu Arg Thr Gly Asn Met Arg
210 215 220Glu Phe Ile Asn Ser Pro Phe Arg Asp Ile Tyr Tyr Arg Gly Gln Thr225 230 235 240Ser Leu His Ile Ala Ile Glu Arg Arg Cys Lys His Tyr Val Glu Leu
245 250 255Leu Val Ala Gln Gly Ala Asp Val His Ala Gln Ala Arg Gly Arg Phe
260 265 270Phe Gln Pro Lys Asp Glu Gly Gly Tyr Phe Tyr Phe Gly Glu Leu Pro
275 280 285Leu Ser Leu Ala Ala Cys Thr Asn Gln Pro His Ile Val Asn Tyr Leu
290 295 300Thr Glu Asn Pro His Lys Lys Ala Asp Met Arg Arg Gln Asp Ser Arg305 310 315 320Gly Asn Thr Val Leu His Ala Leu Val Ala Ile Ala Asp Asn Thr Arg
325 330 335Glu Asn Thr Lys Phe Val Thr Lys Met Tyr Asp Leu Leu Leu Leu Lys
340 345 350Cys Ser Arg Leu Phe Pro Asp Ser Asn Leu Glu Thr Val Leu Asn Asn
355 360 365Asp Gly Leu Ser Pro Leu Met Met Ala Ala Lys Thr Gly Lys Ile Gly
370 375 380Val Phe Gln His Ile Ile Arg Arg Glu Val Thr Asp Glu Asp Thr Arg385 390 395 400His Leu Ser Arg Lys Phe Lys Asp Trp Ala Tyr Gly Pro Val Tyr Ser
405 410 415Ser Leu Tyr Asp Leu Ser Ser Leu Asp Thr Cys Gly Glu Glu Val Ser
420 425 430Val Leu Glu Ile Leu Val Tyr Asn Ser Lys Ile Glu Asn Arg His Glu
435 440 445Met Leu Ala Val Glu Pro Ile Asn Glu Leu Leu Arg Asp Lys Trp Arg
450 455 460Lys Phe Gly Ala Val Ser Phe Tyr Ile Asn Val Val Ser Tyr Leu Cys465 470 475 480Ala Met Val Ile Phe Thr Leu Thr Ala Tyr Tyr Gln Pro Leu Glu Gly
485 490 495Thr Pro Pro Tyr Pro Tyr Arg Thr Thr Val Asp Tyr Leu Arg Leu Ala
500 505 510Gly Glu Val Ile Thr Leu Phe Thr Gly Val Leu Phe Phe Phe Thr Ser
515 520 525Ile Lys Asp Leu Phe Thr Lys Lys Cys Pro Gly Val Asn Ser Leu Phe
530 535 540Val Asp Gly Ser Phe Gln Leu Leu Tyr Phe Ile Tyr Ser Val Leu Val545 550 555 560Val Val Ser Ala Ala Leu Tyr Leu Ala Gly Ile Glu Ala Tyr Leu Ala
565 570 575Val Met Val Phe Ala Leu Val Leu Gly Trp Met Asn Ala Leu Tyr Phe
580 585 590Thr Arg Gly Leu Lys Leu Thr Gly Thr Tyr Ser Ile Met Ile Gln Lys
595 600 605Ile Leu Phe Lys Asp Leu Phe Arg Phe Leu Leu Val Tyr Leu Leu Phe
610 615 620Met Ile Gly Tyr Ala Ser Ala Leu Val Thr Leu Leu Asn Pro Cys Thr625 630 635 640Asn Met Lys Val Cys Asp Glu Asp Gln Ser Asn Cys Thr Val Pro Thr
645 650 655Tyr Pro Ala Cys Arg Asp Ser Glu Thr Phe Ser Ala Phe Leu Leu Asp
660 665 670Leu Phe Lys Leu Thr Ile Gly Met Gly Asp Leu Glu Met Leu Ser Ser
675 680 685Ala Lys Tyr Pro Val Val Phe Ile Leu Leu Leu Val Thr Tyr Ile Ile
690 695 700Leu Thr Phe Val Leu Leu Leu Asn Met Leu Ile Ala Leu Met Gly Glu705 710 715 720Thr Val Gly Gln Val Ser Lys Glu Ser Lys His Ile Trp Lys Leu Gln
725 730 735Trp Ala Thr Thr Ile Leu Asp Ile Glu Arg Ser Phe Pro Val Phe Leu
740 745 750Arg Lys Ala Phe Arg Ser Gly Glu Met Val Thr Val Gly Lys Ser Ser
755 760 765Asp Gly Thr Pro Asp Arg Arg Trp Cys Phe Arg Val Asp Glu Val Ser
770 775 780Trp Ser His Trp Asn Gln Asn Leu Gly Ile Ile Asn Glu Asp Pro Gly785 790 795 800Lys Ser Glu Ile Tyr Gln Tyr Tyr Gly Phe Ser His Thr Val Gly Arg
805 810 815Leu Arg Arg Asp Arg Trp Ser Ser Val Val Pro Arg Val Val Glu Leu
820 825 830Asn Lys Asn Ser Ser Ala Asp Glu Val Val Val Pro Leu Asp Asn Leu
835 840 845Gly Asn Pro Asn Cys Asp Gly His Gln Gln Gly Tyr Ala Pro Lys Trp
850 855 860Arg Thr Asp Asp Ala Pro Leu865 870<210>2<211>2616<212>DNA<213>小鼠<400> 2atggcagatc ctggtgatgg tccccgtgca gcgcctgggg aggtggctga gccccctgga 60gatgagagtg gtacctctgg tggggaggcc ttccccctct cttccctggc caatctgttt 120gagggggagg aaggctcctc ttctctttcc ccggtggatg ctagccgccc tgctggccct 180ggcgatggac gtccaaacct gcgtatgaag ttccagggcg ctttccgcaa gggggttccc 240aaccccattg acctgttgga gtccaccctg tacgagtcct cagtagtgcc tgggcccaag 300aaagcgccca tggattcctt gttcgactac ggcacttacc gtcaccaccc cagtgacaac 360aagagatgga ggagaaaggt cgtggagaag cagccacaga gccccaaaac tcctgcaccc 420cagccacccc ccatcctcaa agtcttcaat cggcccatcc tctttgacat tgtgtcccgg 480ggctccactg cggacctaga tggactgctc tccttcttgt tgacccacaa gaagcgcctg 540actgatgagg agttccggga gccgtccacg gggaagacct gcctgcccaa ggcgctgctg 600aacctaagca acgggcgcaa cgacaccctc caggtgttgc tggacattgc ggagcgcacc 660ggcaacatgc gtgaattcat caactcgccc ttcagagaca tctactaccg aggccagaca 720tccctgcaca ttgccatcga acggcgctgc aagcactacg tggagctgct ggtggcccag 780ggagccgacg tgcacgccca ggcccgcggc cgcttcttcc agcccaagga tgagggaggc 840tacttctact ttggggagct gcccttgtcc ctggcagcct gcaccaacca gccgcacatc 900gtcaactacc tgacagagaa ccctcacaag aaagctgaca tgaggcgaca ggactcgagg 960gggaacacgg tgctgcacgc gctggtggcc atcgccgaca acacccgaga gaacaccaag 1020tttgtcacca agatgtacga cctgctgctt ctcaagtgtt cacgcctctt ccccgacagc 1080aacctggaga cagttctcaa caatgatggc ctttcgcctc tcatgatggc tgccaagaca 1140ggcaagatcg gggtctttca gcacatcatc cgacgtgagg tgacagatga ggacacccgg 1200catctgtctc gcaagttcaa ggactgggcc tatgggcctg tgtattcttc tctctacgac 1260ctctcctccc tggacacatg cggggaggag gtgtccgtgc tggagatcct ggtgtacaac 1320agcaagatcg agaaccgcca tgagatgctg gctgtagagc ccattaacga actgttgaga 1380gacaagtggc gtaagtttgg ggctgtgtcc ttctacatca acgtggtctc ctatctgtgt 1440gccatggtca tcttcaccct caccgcctac tatcagccac tggagggcac gccaccctac 1500ccttaccgga ccacagtgga ctacctgagg ctggctggcg aggtcatcac gctcttcaca 1560ggagtcctgt tcttctttac cagtatcaaa gacttgttca cgaagaaatg ccctggagtg 1620aattctctct tcgtcgatgg ctccttccag ttactctact tcatctactc tgtgctggtg 1680gttgtctctg cggcgctcta cctggctggg atcgaggcct acctggctgt gatggtcttt 1740gccctggtcc tgggctggat gaatgcgctg tacttcacgc gcgggttgaa gctgacgggg 1800acctacagca tcatgattca gaagatcctc ttcaaagacc tcttccgctt cctgcttgtg 1860tacctgctct tcatgatcgg ctatgcctca gccctggtca ccctcctgaa tccgtgcacc 1920aacatgaagg tctgtgacga ggaccagagc aactgcacgg tgcccacgta tcctgcgtgc 1980cgcgacagcg agaccttcag cgccttcctc ctggacctct tcaagctcac catcggcatg 2040ggagacctgg agatgctgag cagcgccaag taccccgtgg tcttcatcct cctgctggtc 2100acctacatca tcctcacctt cgtgctcctg ttgaacatgc ttatcgccct catgggtgag 2160accgtgggcc aggtgtccaa ggagagcaag cacatctgga agttgcagtg ggccaccacc 2220atcctggaca tcgagcgttc cttccctgtg ttcctgagga aggccttccg ctccggagag 2280atggtgactg tgggcaagag ctcagatggc actccggacc gcaggtggtg cttcagggtg 2340gacgaggtga gctggtctca ctggaaccag aacttgggca tcattaacga ggaccctggc 2400aagagtgaaa tctaccagta ctatggcttc tcccacaccg tggggcgcct tcgtagggat 2460cgttggtcct cggtggtgcc ccgcgtagtg gagctgaaca agaactcaag cgcagatgaa 2520gtggtggtac ccctggataa cctagggaac cccaactgtg acggccacca gcagggctac 2580gctcccaagt ggaggacgga cgatgcccca ctgtag 2616<210>3<211>871<212>PRT<213>智人(Homo sapiens)<400>3Met Ala Asp Ser Ser Glu Gly Pro Arg Ala Gly Pro Gly Glu Val Ala1 5 10 15Glu Leu Pro Gly Asp Glu Ser Gly Thr Pro Gly Gly Glu Ala Phe Pro
20 25 30Leu Ser Ser Leu Ala Asn Leu Phe Glu Gly Glu Asp Gly Ser Leu Ser
35 40 45Pro Ser Pro Ala Asp Ala Ser Arg Pro Ala Gly Pro Gly Asp Gly Arg
50 55 60Pro Asn Leu Arg Met Lys Phe Gln Gly Ala Phe Arg Lys Gly Val Pro65 70 75 80Asn Pro Ile Asp Leu Leu Glu Ser Thr Leu Tyr Glu Ser Ser Val Val
85 90 95Pro Gly Pro Lys Lys Ala Pro Met Asp Ser Leu Phe Asp Tyr Gly Thr
100 105 110Tyr Arg His His Ser Ser Asp Asn Lys Arg Trp Arg Lys Lys Ile Ile
115 120 125Glu Lys Gln Pro Gln Ser Pro Lys Ala Pro Ala Pro Gln Pro Pro Pro
130 135 140Ile Leu Lys Val Phe Asn Arg Pro Ile Leu Phe Asp Ile Val Ser Arg145 150 155 160Gly Ser Thr Ala Asp Leu Asp Gly Leu Leu Pro Phe Leu Leu Thr His
165 170 175Lys Lys Arg Leu Thr Asp Glu Glu Phe Arg Glu Pro Ser Thr Gly Lys
180 185 190Thr Cys Leu Pro Lys Ala Leu Leu Asn Leu Ser Asn Gly Arg Asn Asp
195 200 205Thr Ile Pro Val Leu Leu Asp Ile Ala Glu Arg Thr Gly Asn Met Arg
210 215 220Glu Phe Ile Asn Ser Pro Phe Arg Asp Ile Tyr Tyr Arg Gly Gln Thr225 230 235 240Ala Leu His Ile Ala Ile Glu Arg Arg Cys Lys His Tyr Val Glu Leu
260 265 270Leu Val Ala Gln Gly Ala Asp Val His Ala Gln Ala Arg Gly Arg Phe
260 265 270Phe Gln Pro Lys Asp Glu Gly Gly Tyr Phe Tyr Phe Gly Glu Leu Pro
275 280 285Leu Ser Leu Ala Ala Cys Thr Asn Gln Pro His Ile Val Asn Tyr Leu
290 295 300Thr Glu Asn Pro His Lys Lys Ala Asp Met Arg Arg Gln Asp Ser Arg305 310 315 320Gly Asn Thr Val Leu His Ala Leu Val Ala Ile Ala Asp Asn Thr Arg
325 330 335Glu Asn Thr Lys Phe Val Thr Lys Met Tyr Asp Leu Leu Leu Leu Lys
340 345 350Cys Ala Arg Leu Phe Pro Asp Ser Asn Leu Glu Ala Val Leu Asn Asn
355 360 365Asp Gly Leu Ser Pro Leu Met Met Ala Ala Lys Thr Gly Lys Ile Gly
370 375 380Val Phe Gln His Ile Ile Arg Arg Glu Val Thr Asp Glu Asp Thr Arg385 390 395 400His Leu Ser Arg Lys Phe Lys Asp Trp Ala Tyr Gly Pro Val Tyr Ser
405 410 415Ser Leu Tyr Asp Leu Ser Ser Leu Asp Thr Cys Gly Glu Glu Ala Ser
420 425 430Val Leu Glu Ile Leu Val Tyr Asn Ser Lys Ile Glu Asn Arg His Glu
435 440 445Met Leu Ala Val Glu Pro Ile Asn Glu Leu Leu Arg Asp Lys Trp Arg
450 455 460Lys Phe Gly Ala Val Ser Phe Tyr Ile Asn Val Val Ser Tyr Leu Cys465 470 475 480Ala Met Val Ile Phe Thr Leu Thr Ala Tyr Tyr Gln Pro Leu Glu Gly
485 490 495Thr Val Pro Tyr Pro Tyr Arg Thr Thr Val Asp Tyr Leu Arg Leu Ala
500 505 510Gly Glu Val Ile Thr Leu Phe Thr Gly Val Leu Phe Phe Phe Thr Asn
515 520 525Ile Lys Asp Leu Phe Met Lys Lys Cys Pro Gly Val Asn Ser Leu Phe
530 535 540Ile Asp Gly Ser Phe Gln Leu Leu Ser Phe Ile Tyr Ser Val Leu Val545 550 555 560Ile Val Ser Ala Ala Leu Tyr Leu Ala Gly Ile Glu Ala Tyr Leu Ala
565 570 575Val Met Val Phe Ala Leu Val Leu Gly Trp Met Asn Ala Leu Tyr Phe
580 585 590Thr Arg Gly Leu Lys Leu Thr Gly Thr Tyr Ser Ile Met Ile Gln Lys
595 600 605Val Leu Phe Lys Asp Leu Phe Arg Phe Leu Leu Val Tyr Leu Leu Phe
610 615 620Met Ile Gly Tyr Ala Ser Ala Leu Val Ser Leu Leu Asn Pro Cys Ala625 630 635 640Asn Met Lys Val Cys Asn Glu Asp Gln Thr Asn Cys Thr Val Pro Thr
645 650 655Tyr Pro Ser Cys Arg Asp Ser Glu Thr Phe Ser Thr Phe Leu Leu Asp
660 665 670Leu Phe Lys Leu Thr Ile Gly Met Gly Asp Leu Glu Met Leu Ser Ser
675 680 685Thr Lys Tyr Pro Val Val Phe Ile Ile Leu Leu Val Thr Tyr Ile Ile
690 695 700Leu Thr Phe Val Leu Leu Leu Asn Met Leu Ile Ala Leu Met Gly Glu705 710 715 720Thr Val Gly Gln Val Ser Lys Glu Ser Lys His Ile Trp Lys Leu Gln
725 730 735Trp Ala Thr Thr Ile Leu Asp Ile Glu Arg Ser Phe Pro Val Phe Leu
740 745 750Arg Lys Ala Phe Arg Ser Gly Glu Met Val Thr Val Gly Lys Ser Ser
755 760 765Asp Gly Thr Pro Asp Arg Arg Trp Cys Phe Arg Val Asn Glu Val Asn
770 775 780Trp Ser His Trp Asn Gln Asn Leu Gly Ile Ile Asn Glu Asp Pro Gly785 790 795 800Lys Asn Glu Thr Tyr Gln Tyr Tyr Gly Phe Ser His Thr Val Gly Arg
805 810 815Leu Arg Met Asp Arg Trp Ser Ser Val Val Pro Arg Val Val Glu Leu
820 825 830Asn Lys Asn Ser Asn Pro Asp Glu Val Val Val Pro Leu Asp Ser Met
835 840 845Gly Asn Pro Arg Cys Asp Gly His Gln Gln Gly Tyr Pro Arg Lys Trp
850 855 860Arg Thr Asp Asp Ala Pro Leu865 870<210>4<211>2616<212>DNA<213>智人(Homo sapiens)<400>4atggcggatt ccagcgaagg cccccgcgcg gggcccgggg aggtggctga gctccccggg 60gatgagagtg gcaccccagg tggggaggct tttcctctct cctccctggc caatctgttt 120gagggggagg atggctccct ttcgccctca ccggctgatg ccagtcgccc tgctggccca 180ggcgatgggc gaccaaatct gcgcatgaag ttccagggcg ccttccgcaa gggggtgccc 240aaccccatcg atctgctgga gtccacccta tatgagtcct cggtggtgcc tgggcccaag 300aaagcaccca tggactcact gtttgactac ggcacctatc gtcaccactc cagtgacaac 360aagaggtgga ggaagaagat catagagaag cagccgcaga gccccaaagc ccctgcccct 420cagccgcccc ccatcctcaa agtcttcaac cggcctatcc tctttgacat cgtgtcccgg 480ggctccactg ctgacctgga cgggctgctc ccattcttgc tgacccacaa gaaacgccta 540actgatgagg agtttagaga gccatctacg gggaagacct gcctgcccaa ggccttgctg 600aacctgagca atggccgcaa cgacaccatc cctgtgctgc tggacatcgc ggagcgcacc 660ggcaacatga gggagttcat taactcgccc ttccgtgaca tctactatcg aggtcagaca 720gccctgcaca tcgccattga gcgtcgctgc aaacactacg tggaacttct cgtggcccag 780ggagctgatg tccacgccca ggcccgtggg cgcttcttcc agcccaagga tgaggggggc 840tacttctact ttggtgagct gcccctgtcg ctggctgcct gcaccaacca gccccacatt 900gtcaactacc tgacggagaa cccccacaag aaggcggaca tgcggcgcca ggactcgcga 960ggcaacacag tgctgcatgc gctggtggcc attgctgaca acacccgtga gaacaccaag 1020tttgttacca agatgtacga cctgctgctg ctcaagtgtg cccgcctctt ccccgacagc 1080aacctggagg ccgtgctcaa caacgacggc ctctcgcccc tcatgatggc tgccaagacg 1140ggcaagattg gggtgtttca gcacatcatc cggcgggagg tgacggatga ggacacacgg 1200cacctgtccc gcaagttcaa ggactgggcc tatgggccag tgtattcctc gctttatgac 1260ctctcctccc tggacacgtg tggggaagag gcctccgtgc tggagatcct ggtgtacaac 1320agcaagattg agaaccgcca cgagatgctg gctgtggagc ccatcaatga actgctgcgg 1380gacaagtggc gcaagttcgg ggccgtctcc ttctacatca acgtggtctc ctacctgtgt 1440gccatggtca tcttcactct caccgcctac taccagccgc tggagggcac agtgccgtac 1500ccttaccgca ccacggtgga ctacctgcgg ctggctggcg aggtcattac gctcttcact 1560ggggtcctgt tcttcttcac caacatcaaa gacttgttca tgaagaaatg ccctggagtg 1620aattctctct tcattgatgg ctccttccag ctgctcagct tcatctactc tgtcctggtg 1680atcgtctcag cagccctcta cctggcaggg atcgaggcct acctggccgt gatggtcttt 1740gccctggtcc tgggctggat gaatgccctt tacttcaccc gtgggctgaa gctgacgggg 1800acctatagca tcatgatcca gaaggtactc ttcaaggacc ttttccgatt cctgctcgtc 1860tacttgctct tcatgatcgg ctacgcttca gccctggtct ccctcctgaa cccgtgtgcc 1920aacatgaagg tgtgcaatga ggaccagacc aactgcacag tgcccactta cccctcgtgc 1980cgtgacagcg agaccttcag caccttcctc ctggacctgt ttaagctgac catcggcatg 2040ggcgacctgg agatgctgag cagcaccaag taccccgtgg tcttcatcat cctgctggtg 2100acctacatca tcctcacctt tgtgctgctc ctcaacatgc tcattgccct catgggcgag 2160acagtgggcc aggtctccaa ggagagcaag cacatctgga agctgcagtg ggccaccacc 2220atcctggaca ttgagcgctc cttccccgta ttcctgagga aggccttccg ctctggggag 2280atggtcaccg tgggcaagag ctcggacggc actcctgacc gcaggtggtg cttcagggtg 2340aatgaggtga actggtctca ctggaaccag aacttgggca tcatcaacga ggacccgggc 2400aagaatgaga cctaccagta ttatggcttc tcgcataccg tgggccgcct ccgaatggat 2460cgctggtcct cggtggtacc ccgcgtggtg gaactgaaca agaactcgaa cccggacgag 2520gtggtggtgc ctctggacag catggggaac ccccgctgcg atggccacca gcagggttac 2580ccccgcaagt ggaggactga tgacgccccg ctctag 2616<210>5<211>19<212>DNA<213>人工序列<220><223>人工序列的描述:合成的DNA<400>5gagagaacac caagtttgt 19<210>6<211>26<212>DNA<213>人工序列<220><223>人工序列的描述:合成的DNA<400>6cagcggcccc aatctcttca aagtac 26<210>7<211>20<212>DNA<213>人工序列<220><223>人工序列的描述:合成的DNA<400>7ctacagccag catctcatgg 20<210>8<211>30<212>DNA<213>人工序列<220><223>人工序列的描述:合成的DNA<400>8tcagggtcca gtatggcaga tcctggtgat 30<210>9<211>22<212>DNA<213>人工序列<220><223>人工序列的描述:合成的DNA<400>9gttaatgggc tctacagcca gc 22<210>10<211><212>PRT<213>智人(Homo sapiens)<400>10Pro Leu Asp Asn Leu Gly Asn Pro Asn Cys1 5 10
Claims (14)
1.一种蛋白质,所述蛋白在肾脏中特异性表达,具有对机械刺激应答而非选择性地将阳离子摄入细胞内的功能。
2.根据权利要求1所述的蛋白质,所述蛋白质从小鼠衍生获得。
3.根据权利要求2所述的蛋白质,它具有序列表SEQ ID NO:1所示的氨基酸序列。
4.一种DNA,它编码权利要求3中所述的氨基酸序列。
5.根据权利要求4所述的DNA,它具有序列表SEQ ID NO:2所示的核苷酸序列。
6.根据权利要求1所述的蛋白质,所述蛋白质从人衍生获得。
7.根据权利要求6所述的蛋白质,它具有序列表SEQ ID NO:3所示的氨基酸序列。
8.一种DNA,它编码权利要求7所述的氨基酸序列。
9.根据权利要求8所述的DNA,它具有序列表SEQ ID NO:4所示的核苷酸序列。
10.一种蛋白质,它具有权利要求3或7所述的蛋白质氨基酸序列中一个或多个氨基酸缺失、置换或增加的氨基酸序列。
11.一种DNA,它是与权利要求4、5、8或9所述的DNA杂交的DNA。
12.一种筛选促进或阻滞阳离子通道的物质的方法,该方法采用权利要求1、2、3、6或7所述的蛋白质。
13.一种抗体,它是针对权利要求1、2、3、6或7所述的蛋白质的抗体。
14.根据权利要求13所述的抗体,它是单克隆抗体。
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JP2000048727 | 2000-02-25 |
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CN01805652A Pending CN1432062A (zh) | 2000-02-25 | 2001-02-23 | 新的蛋白质及编码该蛋白质的基因 |
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US (1) | US20030073117A1 (zh) |
EP (1) | EP1260585A4 (zh) |
JP (1) | JPWO2001062915A1 (zh) |
KR (1) | KR20030004354A (zh) |
CN (1) | CN1432062A (zh) |
AU (1) | AU2001234150A1 (zh) |
CA (1) | CA2400876A1 (zh) |
HU (1) | HUP0300489A3 (zh) |
NO (1) | NO20024029L (zh) |
WO (1) | WO2001062915A1 (zh) |
Cited By (1)
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CN102199197A (zh) * | 2011-04-13 | 2011-09-28 | 安徽医科大学 | 一种具有自组装钾通道功能的多肽及其应用 |
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PL213159B1 (pl) | 2010-04-23 | 2013-01-31 | Inst Biolog Doswiadczalnej Im Marcelego Nenckiego Pan | Zmutowane szczepy Escherichia coli, sposób testowania potencjalnych zwiazków antybakteryjnych wykorzystujacy te szczepy oraz zestaw do testowania |
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AU742391B2 (en) * | 1997-08-20 | 2002-01-03 | Regents Of The University Of California, The | Nucleic acid sequences encoding capsaicin receptor and capsaicin receptor-related polypeptides and uses thereof |
AU2466799A (en) * | 1998-01-22 | 1999-08-09 | Regents Of The University Of California, The | Nucleic acid sequences encoding capsaicin receptors |
GB9826359D0 (en) * | 1998-12-01 | 1999-01-27 | Glaxo Group Ltd | Novel receptors |
EP1144628A3 (en) * | 1999-11-12 | 2002-02-27 | Abbott Laboratories | Human vanilloid receptor gene |
US20020072101A1 (en) * | 2000-01-21 | 2002-06-13 | Gaughan Glen T. | Novel human nucleic acid molecules and polypeptides encoding cation channels |
US6455278B1 (en) * | 2000-02-08 | 2002-09-24 | Ortho-Mcneil Pharmaceutical, Inc. | DNA encoding human vanilloid receptor VR3 |
EP1170365A1 (en) * | 2000-07-04 | 2002-01-09 | Smithkline Beecham Plc | Member of the ion channel family of polypeptides; vanilrep4 |
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2001
- 2001-02-23 WO PCT/JP2001/001354 patent/WO2001062915A1/ja not_active Application Discontinuation
- 2001-02-23 KR KR1020027010913A patent/KR20030004354A/ko not_active Application Discontinuation
- 2001-02-23 JP JP2001562689A patent/JPWO2001062915A1/ja active Pending
- 2001-02-23 HU HU0300489A patent/HUP0300489A3/hu unknown
- 2001-02-23 AU AU2001234150A patent/AU2001234150A1/en not_active Abandoned
- 2001-02-23 CN CN01805652A patent/CN1432062A/zh active Pending
- 2001-02-23 CA CA002400876A patent/CA2400876A1/en not_active Abandoned
- 2001-02-23 EP EP01906253A patent/EP1260585A4/en not_active Withdrawn
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2002
- 2002-08-23 US US10/227,255 patent/US20030073117A1/en not_active Abandoned
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
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CN102199197A (zh) * | 2011-04-13 | 2011-09-28 | 安徽医科大学 | 一种具有自组装钾通道功能的多肽及其应用 |
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HUP0300489A3 (en) | 2006-06-28 |
EP1260585A4 (en) | 2005-02-02 |
HUP0300489A2 (hu) | 2003-08-28 |
KR20030004354A (ko) | 2003-01-14 |
WO2001062915A1 (fr) | 2001-08-30 |
EP1260585A1 (en) | 2002-11-27 |
JPWO2001062915A1 (ja) | 2004-01-08 |
NO20024029D0 (no) | 2002-08-23 |
CA2400876A1 (en) | 2001-08-30 |
US20030073117A1 (en) | 2003-04-17 |
AU2001234150A1 (en) | 2001-09-03 |
NO20024029L (no) | 2002-10-24 |
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