在转基因植物中产生载脂蛋白的方法

专利名称：在转基因植物中产生载脂蛋白的方法
技术领域：
本发明涉及植物遗传工程方法，以及载脂蛋白之生产。更具体而言，本发明涉及在转基因植物中生产重组体载脂蛋白之方法。
背景技术：
在健康的人体内，胆固醇的输送和清除之间维持平衡。当人体的低密度脂蛋白(LDL)含量高，而高密度脂蛋白(HDL)含量低时，不平衡造成沉积在动脉内的胆固醇比清除的多(M.J.Van Dam等人2002年，Lancet 35937-42)。动脉粥样硬化(动脉狭窄或阻塞)，是胆固醇一再沉积的结果，称为动脉粥样斑(A.S.Major等人2001年，Arterioscler.Thromb.Vasc.Biol.211790-1795)。
脂蛋白可分成致动脉粥样化脂蛋白和血管保护性脂蛋白，致动脉粥样化脂蛋白一般都是含载脂蛋白(Apo)B的脂蛋白，例如极低密度脂蛋白(VLDL)、中度(IDL)、低(LDL)或脂蛋白(Lp(a))，而血管保护性脂蛋白含Apo AI，例如为HDL。
HDL主要蛋白成份之Apo AI，在胆固醇体内稳态上扮演关键性角色。以临床和人群为基础的研究已证明，在心脏血管疾病和血浆HDL含量之间，有明显的反相关性，而提示Apo AI和HDL有抗动脉粥样化形成的保护性作用(H.B.Rubins等人1993年，Am.J.Cartiol 7145-52)。对易感受动脉粥样硬化的转基因小鼠(E.M.Rubin等人1991年，Nature 353265-267)和兔(N.Duverger等人1996年，Circulation 94713-717)研究，已显示人类Apo AI的表达，可抑制动脉粥样硬化的发展。此效果可能与其有效促进胆固醇从细胞溢出有关(G.Castro等人1997年，Biochemistry 362243-2249)，这是”“逆向胆固醇转运(RCT)”过程中的第一步(J.A.Glomset 1968年，J.Lipid Res.9155-167)。Apo AI作为细胞胆固醇的优先接纳体，而调节此过程(G.H.Rothblat等人1999年，J.Lipid Res.40781-796)，提高HDL相关胆固醇的卵磷脂—胆固醇—酰基转移酶(LCAT)活性若干倍(A.Jonas 1991年，Biochem.Biophys.Acta 1084205-220；R.W.Mahley等人1984年，J.Lipid Res.251277-1294)，而将LACT衍生的胆固醇酯转运到肝(J.R.Morrison等人1992年，J.Biol.Chem.26713205-13209)。
例如LIPITOR_(阿托伐他汀钙)等合成抗高血脂剂的作用是通过抑制胆固醇合以降低脂质含量(P.Alaupovic等人1997年，Atherosclerosis 133123-133)，不同的是，注入纯化的Apo AI会刺激胆固醇从组织溢出，进入血浆内(M.Navab等人2002年，Circulation105290-292)。这提示Apo AI会刺激胆固醇从动脉管壁内的泡沫细胞溢出，而诱导动脉粥样斑的退化，有效“清扫”动脉。
人体在肝脏和肠细胞内合成Apo AI，作为非糖基化前蛋白原(pre-pro-protein)(J.I.Gordon等人1983年，J.Biol.Chem.2584037-4044)。蛋白离开细胞之前，18个氨基酸的前段被除去，而在分泌后，通过血浆内的未知蛋白酶，6个氨基酸的前段被裂解，留下成熟的243个氨基酸的蛋白质(K.Saku等人1999年，Eur.J.Clin.Invest.29196-203)。
载脂蛋白A-IMilano(Apo AI-M)为首先记载的人体Apo AI的分子变异体(G.Franceschini等人1980年，J.Clin.Invest.66892-900)。其特征是Arg 173以Cys取代(K.H.Weisgraber等人1983年，J.Biol.Chem.2582508-2513)。突变体载脂蛋白作为常染色体显性性状而传递，而有8代携带者已告鉴定(G.C.Gerli等人1984年，Hum.Hered.34133-140)。
携带Apo AI-M的个体具有明显降低的HDL胆固醇水平的特征。尽管如此，受到影响的对象未明显显示任何增加动脉疾病的危机；诚然，通过检验基因系统图谱，显示此等对象会受到”“保护”，以免遭受动脉粥样硬化。
Apo AI-M在载体内可能保护性效果的机制，似乎与突变载脂蛋白结构的改变有关，会失去一α螺旋，而增加疏水性残基的暴露(G.Franceschini等人1985年，J.Biol.Chem.26016321-16325)。丢失α螺旋的紧密结构，导致增加分子的柔性，较之正常A-I，更轻易与脂质结合。此外，载脂蛋白/脂质结合物更易变性，因此在突变体情况下，亦改进脂质输送。
治疗上使用Apo AI和Apo AI-M突变体，目前受到的限制是缺乏可以制备足量的和适当形式的该载脂蛋白的方法。尤其是Apo AI重组体的生产显示很难，由于其两性分子的特性、自动聚集和降解之故(H.H.Schmidt等人1997年，Protein Expr.Purif.10226-236)。在本发明之时，人体Apo AI重组体已在两个真核生物系统的体外表达即杆菌病毒转染的草地夜蛾(Spodoptera frugiperda)(Sf9)细胞(M.G.Sorci-Thomas等人1996年，J.Lipid Res.37673-683)，以及稳定转染中国仓鼠卵巢(CHO)细胞(T.M.Forte等人1990年，Biochim.Biophys.Acta104711-18；J.B.Mallory等人1987年，J.Biol.Chem.2624241-4247)。在杆菌病毒系统中，一旦细胞成功转染，在正确构建体的细胞用于表达之前，要有深入筛选的过程。同理，CHO细胞集落必须进行筛选过程，以找出稳定转染的高度表达集落。此外，凡此二种细胞类型在达到明显表达之前，需要较长时间期限，其保养水平远较细菌为高。
细菌系统内蛋白质的重组体表达一般具有吸引力，因为可快速而经济生成大量纯蛋白。对于转化的大肠杆菌(Escherichia coli)内的ApoAI表达有若干报告；然而，一般而言，近来在表达水平方面有一些改进(R.O.Ryan等人2003年，Protein Expr.Purif.2798-103)，此等方法提供较低产率，或有外来亲和性标记或分泌信号之不良存在(J.Bergeron等人1997年，Biochim.Biophys.Acta 1344139-152；H.H.Li等人2001年，J.Lipid Res.422084-2091；K.A.McGuire等人1996年，J.Lipid Res.371519-1528)。此外，已知大肠杆菌内毒素与载脂蛋白形成特强复合体(Emancipator等人(1992)，Infect.Immun.60596-601)。在载脂蛋白的制药制剂内，与此等大肠杆菌内毒素相关的毒性亟需减少或消除，除去此等内毒素，同时在技术上有可行性，不过其涉及复杂而昂贵的蛋白纯化方法(美国专利6,506,879号)，不完全消除对人体健康的危险。
本领域已知使用植物为大量生产重组体蛋白之生物反应器，业已生产过许多蛋白质，包含人体治疗用蛋白质。例如，美国专利4,956,282；5,550,038和5,629,175号揭示在植物内生产γ-干扰素；美国专利5,650,307；5,716,802和5,763,748号详细描述了在植物内生产人血清白蛋白，而美国专利5,202,422；5,639,947和5,959,177号涉及在植物内生产抗体。以植物为基本的重组体蛋白生产系统具有的重大优点之一，是提高成长植物的英亩数，可以便宜方式把蛋白生产规模化到提供大量蛋白质。反之，发酵和细胞培养系统的空间、设备和能量需求大，使得生产成本增加。然而，尽管事实上使用植物为生物反应器已有充分文献，且尽管有上述治疗上应用载脂蛋白，然而现有技术尚未能提供在植物内生产载脂蛋白之方法。
为了给以发酵和细胞培养基为基础的系统提供实用的其他方法，重要的是植物要保留健康，且载脂蛋白可在植物内累积到明显的水平。有鉴于载脂蛋白与脂质相关之固有性质，以重组方式表达的载脂蛋白会与内源性植物脂质相关，因而干扰到植物脂质之新陈代谢。因此，载脂蛋白的重组体表达会影响到植物健康。另外，以重组方式表达的载脂蛋白，会无法累积到有效水平，一如保护性机制在载脂蛋白降解中所致。因此，植物的合成能力是否以及如何在植物内达成商业化生产，尚未明了。
因此，有鉴于利用现有技术重组生产载脂蛋白方法相关之缺点，在本领域需要改进载脂蛋白之生产方法。

发明内容
本发明涉及在植物中生产载脂蛋白的方法。本发明尤其涉及在植物种子内生产载脂蛋白之方法。
因此，本发明提供了在植物中表达载脂蛋白的方法，包括(a)提供嵌合核酸构建体，其包括在5’至3’的转录方向可操作连接的下列成份(i)能够控制在植物细胞内表达之核酸序列；和(ii)编码载脂蛋白多肽之核酸序列；(b)把嵌合核酸构建体导入植物细胞内；以及(c)让植物细胞成长为能够表达载脂蛋白之成熟植物。
按照本发明，已发现植物种子特别适用于生产载脂蛋白。因此，本发明提供在植物种子内表达载脂蛋白之方法，包括(a)提供嵌合核酸构建体，其包括在5’至3’转录方向可操作连接的下列成份(i)能够控制在植物种子细胞内表达之核酸序列；和(ii)编码载脂蛋白多肽之核酸序列；(b)把嵌合核酸构建体导入植物细胞内；以及(c)让植物细胞成长为能够结籽之成熟植物，其中种子表达载脂蛋白。
在进一步优选的实施方式中，能够控制在植物种子细胞内表达的核酸序列，是种子优选的启动子，例如菜豆蛋白(phaseolin)启动子。在优选的实施方式中，总共种子蛋白质的至少0.25％是载脂蛋白。
在本发明优选的实施方式中，嵌合核酸序列还包括编码稳定多肽之核酸序列，其符合读框地连接于编码载脂蛋白之核酸序列。稳定多肽优选地是载脂蛋白不存在时，在植物细胞内可轻易表达和稳定累积之多肽，稳定蛋白可为植物特异性或非植物特异性。按照本发明，可用之植物特异性稳定多肽，包含油体蛋白和硫氧还蛋白。本发明可用之非植物特异性稳定多肽，包含绿色荧光蛋白(GFP)，以及单链抗体或其片段。植物特异性或非植物特异性稳定多肽，经由可裂解释出游离天然型载脂蛋白之接头，连接到载脂蛋白。
嵌合核酸序列优选地还包括导向信号，其方式是载脂蛋白多肽累积在内质网(ER)，或与ER衍生的贮存小泡，例如植物细胞内的油体相关。因此，嵌合核酸构建体另外可包括编码多肽之核酸序列，所述多肽能够把载脂蛋白导向ER或ER衍生之贮存小泡。可用来把载脂蛋白导向ER的核酸序列，包含例如编码KDEL、HDEL、SDEL序列之核酸序列。可用来把载脂蛋白导向油体的核酸序列，包含编码油体蛋白，例如油质蛋白(oleosins)之核酸序列。此外，按照本发明，载脂蛋白可通过表达载脂蛋白而导向油体，其方式为载脂蛋白不含导向信号，但条件是编码载脂蛋白之核酸序列包括载脂蛋白前肽。
在另一优选的实施方式中，嵌合核酸包括导向信号，其方式使得载脂蛋白累积在质外体(apoplast)。因此，在如此实施方式中，嵌合核酸构建体优选地又含有编码一多肽之核酸序列，该多肽能够把载脂蛋白多肽导向质外体。
在又一优选的实施方式中，编码载脂蛋白的核酸序列，其表达方式是使载脂蛋白累积在细胞质内。在如此实施方式中，核酸序列不包括导向信号。
在又一优选的实施方式中，嵌合核酸构建体是在核基因组整合条件下导入植物细胞内。在如此条件下，嵌合核酸序列稳定整合于植物基因组内。
在又一优选的实施方式中，对编码载脂蛋白之核酸序列按照植物密码子进行优化。本发明所用优选的核酸序列，编码人、牛或猪的载脂蛋白A-I和前载脂蛋白A-I。
在另一方面中，本发明提供获得包括载脂蛋白的植物种子之方法。因此，按照本发明，提供获得植物种子之方法，包括(a)提供嵌合核酸构建体，其包括在5’至3’转录方向可操作连接的下列成份(i)能够控制在植物组织细胞内表达之核酸序列；和(ii)编码载脂蛋白多肽之核酸序列；(b)把嵌合核酸构建体导入植物细胞内；(c)让植物细胞生成为可结籽之成熟植物；以及(d)从该植物获得种子，其中种子包括载脂蛋白。
种子可用来获得子代植物之群体，各包括多种表达载脂蛋白的种子。本发明亦提供能够结籽的表达载脂蛋白的植物。在本发明优选的实施方式中，能够结籽的植物包括嵌合核酸序列，其在5’至3’转录方向包括(a)第一核酸序列，能够控制植物细胞内之表达，其可操作地连接于；(b)第二核酸序列，编码载脂蛋白多肽，其中细胞含有载脂蛋白。
在优选的实施方式中，嵌合核酸序列整合于植物核基因组内。
在本发明另一实施方式内，所用植物为拟南芥植物，而在特别优选的实施方式中，植物是红花植物。
在另一方面中，本发明提供了表达载脂蛋白的植物种子。在本发明优选的实施方式中，植物种子包括嵌合核酸序列，其在5’至3’转录方向包括(a)第一核酸序列，能够控制植物细胞内之表达，其可操作地连接于；(b)第二核酸序列，编码载脂蛋白多肽。
种子是所需载脂蛋白多肽的来源，由种子细胞所合成，可提取并获得多少为纯的形式。载脂蛋白可用来治疗血管疾病。
本发明其它特点和优点由以下详述即可轻易明了。然而，须知详细说明和特殊实施例虽是表示本发明优选的实施方式，只供说明而已，因为在本发明精神和范围内的各种变化和修饰，凡本领域人员从详细中都可了然。


现结合以下附图阐述本发明1图1(A)为人类载脂蛋白A-I(Apo AI)的核苷酸序列(SEQ IDNO1)和推定的氨基酸序列(SEQ ID NO2)(感谢Dr.NormanWong，Calgary Alberta提供)(编号NM 000039)。黑体残基代表前序列信号肽，划线残基表示序列原(pro-sequence)。(B)为天然变体ApoAIMilano(R173C)的核苷酸序列(SEQ ID NO3)和推定的氨基酸序列(SEQ ID NO4)。黑体/斜体残基代表突变氨基酸。(C)为天然变体Apo AI Paries(R151C)的核苷酸序列(SEQ ID NO5)和推定的氨基酸序列(SEQ ID NO6)。黑体/斜体残基代表突变氨基酸。
2图2为在拟南芥转基因植物中表达载脂蛋白Apo AI而产生的全部双构建体的示意图。(A)导向植物细胞内之细胞质的构建体。(B)导向植物细胞内之油体的构建体。(C-E)导向分泌通路的构建体。(D和E)构建体含保留在内质网内的额外的KDEL序列。(D)含Apo AI前序列或成熟Apo AI的构建体。(E)含可裂解序列的构建体，供释出Apo AI原或成熟Apo AI。图例说明各构建体内所含启动子类型、信号肽和编码序列。
图3(A)的示意图所示为Apo AI-GFP翻译融合构建体内所用GFP编码区之克隆策略。
图3(B)的示意图所示为Apo AI原和成熟编码区以及种子特异性Apo AI-GFP翻译融合构建体之克隆策略。
图3(C)的示意图所示为产生双载体之克隆策略，用于转化土壤杆菌EHA101细胞，以进行Apo AI-GFP之种子特异性细胞质和油体为基础的导向，Apo10和Apo11分别含有导向细胞质之成熟和原型Apo AI-GFP。Apo12和Apo13分别含有导向油体之原型和成熟Apo AI-GFP翻译融合体。
图3(D)的示意图所示为产生双载体之克隆策略，用于转化土壤杆菌EHA101细胞，以进行Apo AI-GFP之种子特异性分泌通路的导向。Apo15和Apo16分别含有导向分泌通路的成熟和原型Apo AI-GFP翻译融合体。
图4(A)的示意图所示为产生双载体之克隆策略，用于转化土壤杆菌EHA101细胞，以进行Apo AI-GFP的组成型细胞质导向。
图4(B)的示意图所示为Apo AI-GFP组成型细胞质导向之克隆策略，Apo18b含有导向细胞质之Apo AI原-GFP翻译融合体。
图5(A)的示意图所示为Apo AI的原型和成熟编码区之克隆策略，以及Apo AI-GFP翻译融合蛋白之组成型表达。
图5(B)的示意图所示为产生双载体之克隆策略，用于转化土壤杆菌EHA101细胞，以进行Apo AI-GFP的组成型分泌通路导向。Apo19和Apo20分别含有导向分泌通路的成熟和原型Apo AI-GFP翻译融合体。
图6的示意图所示为成熟型Apo AI编码区之克隆策略。Apo21供种子特异性导向细胞质，Apo23供种子特异性导向油体，Apo25供种子特异性导向油体，并以裂解序列klip8纯化，和Apo29，供种子特异性导向分泌通路。
图7的示意图所示为原型Apo AI编码区之克隆策略。Apo22供种子特异性导向细胞质，Apo24供种子特异性导向油体。Apo30供种子特异性导向分泌通路，而Apo26供种子特异性导向油体，并以裂解序列klip加以纯化。
图8(A)的示意图所示为除去内部XhoI位点，并含有KDEL信号肽的Apo AI原型编码区之克隆策略。Apo27供种子特异性导向油体，作为与油质蛋白之框内融合体。Apo31和Apo35二者均导向分泌通路，Apo31和Apo35与油质蛋白抗体D9框内融合，Apo35因KDEL信号肽而累积于内质网。
图8(B)的示意图所示为原型Apo AIMiano编码区之编码策略。Apo27M供Apo AIMilano种子特异性导向油体，作为与油质蛋白框内融合。
图9的示意图所示为除去内部XhoI位点的原型Apo AI编码区之克隆策略。Apo28导向油体且可在klip8序列被裂解，把Apo AI导向分泌通路之Apo32框内融合于油质蛋白抗体D9。
图10的示意图所示为除去内部XhoI位点的原型和成熟型Apo AI编码区之克隆策略，在编码区起始处含有额外的Met残基。Apo34(Apo AI原)和Apo33(成熟Apo AI)导向分泌通路，并与油质蛋白抗体D9框内融合。
图11的示意图所示为原型Apo AI编码区之克隆策略，内部XhoI位点含有KDEL信号肽。Apo36导向分泌通路，并与油质蛋白抗体D9框内融合，因KDEL信号肽而累积于内质网。
图12的示意图所示为除去内部XhoI位点的原型和成熟型Apo AI编码区之克隆策略，在编码区起始处含有额外的Met残基以及KDEL信号肽。Apo38和Apo37导向分泌通路，且与油质蛋白抗体D9框内融合，因KDEL信号肽而累积于内质网。
图13的示意图所示为原型和成熟型Apo AI编码区以及蛋白酶裂解位点之克隆策略。Apo43，Apo44，Apo39和Apo40导向分泌通路，与油质蛋白抗体D9框内融合。Apo43和Apo44因KDEL信号肽而累积于内质网。
图14的示意图所示为在编码区起始处含有额外的Met残基和蛋白酶裂解位点的原型和成熟型Apo AI编码区之克隆策略。Apo42，Apo46，Apo41和Apo45导向分泌通路，与油质蛋白抗体D9框内融合。Apo46和Apo45因KDEL信号肽而累积于内质网。
图15的示意图所示为在编码区起始处含有额外的Met残基的成熟型Apo AI编码区和蛋白酶裂解位点之克隆策略。Apo47与玉米油质蛋白框内融合，供导向油体。
图16为使用多克隆Apo AI抗体的总叶蛋白(A)(25μg)和总种子蛋白(B)(50μg)之蛋白质印迹。Apo17是ubi-mat-Apo AI-GFP构建体。c24叶(25μg)和种子蛋白(50μg)用做阴性对照，而0.5μg人血清白蛋白用做阳性对照。
图17为使用多克隆Apo AI抗体的总叶蛋白(A)(25μg)和总种子蛋白(B)(50μg)之蛋白质印迹。Apo18是ubi-Apo AI原-GFP构建体。c24叶(25μg)和种子蛋白(50μg)用做阴性对照，而0.5μg人血清白蛋白用做阳性对照。
图18为使用多克隆Apo AI抗体的总叶蛋白(A)(25μg)和总种子蛋白(B)(50μg)之蛋白质印迹。Apo19为ubi-PRS-mat-Apo AI-GFP构建体。c24叶(25μg)和种子蛋白(50μg)用做阴性对照，而0.5μg人血清白蛋白用做阳性对照。
图19为使用多克隆Apo AI抗体的总叶蛋白(A)(25μg)和总种子蛋白(B)(50μg)之蛋白质印迹。Apo20为ubi-PRS-Apo AI原-GFP构建体。c24叶(25μg)和种子蛋白(50μg)用做阴性对照，而0.5μg人血清白蛋白用做阳性对照。
图20为使用多克隆GFP抗体的总种子蛋白(50μg)之蛋白质印迹。(A)Apo 10为pha-mat-Apo AI-GFP构建体。(B)Apo11为pha-Apo AI原-GFP构建体。c24种子蛋白(50μg)用做阴性对照，而200ng纯化GFP蛋白用做阳性对照。
图21为使用多克隆GFP抗体的总种子蛋白(50μg)之蛋白质印迹。(A)Apo12为pha-油质蛋白-mat-Apo AI-GFP构建体。(B)Apo13为pha-油质蛋白-Apo AI原-GFP构建体。c24种子蛋白(50μg)用做阴性对照，而200ng纯化GFP蛋白用做阳性对照。
图22为使用多克隆GFP抗体的总种子蛋白(50μg)之蛋白质印迹。(A)Apo15为pha-PRS-mat-Apo AI-GFP构建体。(B)Apo16为pha-PRS-Apo AI原-GFP构建体。c24种子蛋白(50μg)用做阴性对照，而200ng纯化GFP蛋白用做阳性对照。
图23为使用多克隆Apo AI抗体的总种子蛋白(50μg)之蛋白质印迹。(A)Apo21为pha-mat-Apo AI。(B)Apo22为pha-Apo AI原。c24种子蛋白(50μg)用做阴性对照，而0.5μg人血清白蛋白用做阳性对照。
图24为使用多克隆Apo AI抗体的总种子蛋白(50μg)之蛋白质印迹。(A)Apo23为pha-oleo-mat-Apo AI。(B)Apo24为pha-oleo-Apo AI原。c24种子蛋白(50μg)用做阴性对照，而0.5μg人血清白蛋白用做阳性对照。
图25为使用多克隆Apo AI抗体的总种子蛋白(50μg)之蛋白质印迹。(A)Apo25为pha-oleo-klip8-mat-Apo AI(+Met)。(B)Apo26为pha-oleo-klip8-Apo AI原(+Met)。c24种子蛋白(50μg)用做阴性对照，而0.5μg人血清白蛋白用做阳性对照。
图26为使用多克隆Apo AI抗体的总种子蛋白(50μg)之蛋白质印迹。(A)Apo28为pha-oleo-klip8-Apo AI原。(B)Apo29为pha-PRS-mat-Apo AI。c24种子蛋白(50μg)用做阴性对照，而0.5μg人血清白蛋白用做阳性对照。
图27是使用多克隆Apo AI抗体的总种子蛋白(50μg)之蛋白质印迹。(A)Apo30为pha-PRS-Apo AI原。c24种子蛋白(50μg)用做阴性对照，而0.5μg人血清白蛋白用做阳性对照。
图28是使用多克隆Apo AI抗体的总种子蛋白(50μg)之蛋白质印迹。(A)Apo32为pha-PRS-D9 scFv-Apo AI原。(B)Apo33为pha-PRS-D9scFv-mat-Apo AI(+met)。c24种子蛋白(50μg)用做阴性对照，而0.5μg人血清白蛋白用做阳性对照。
图29是使用多克隆Apo AI抗体的总种子蛋白(50μg)之蛋白质印迹。(A)Apo34为pha-PRS-D9 scFv-Apo AI原(+met)。(B)Apo35为pha-PRS-D9 scFv-mat-Apo AI-KDEL。c24种子蛋白(50μg)用做阴性对照，而0.5μg人血清白蛋白用做阳性对照。
图30是使用多克隆Apo AI抗体的总种子蛋白(50μg)之蛋白质印迹。(A)Apo36为pha-PRS-D9 scFv-Apo AI原-KDEL。(B)Apo37为pha-PRS-D9 scFv-mat-Apo AI(+met)-KDEL。c24种子蛋白(50μg)用做阴性对照，而0.5μg人血清白蛋白用做阳性对照。
图31是使用多克隆Apo AI抗体的总种子蛋白(50μg)之蛋白质印迹。(A)Apo38为pha-PRS-D9 scFv-Apo AI原(+met)-KDEL。c24种子蛋白(50μg)用做阴性对照，而0.5μg人血清白蛋白用做阳性对照。(B)Apo29为pha-PRS-D9 scFv-KLIP8-Apo AI。野生型种子用做阴性对照，而得自正常人体血浆(US Biologicals)的3μg人体Apo AI用做阳性对照。
图32是使用多克隆Apo AI抗体的总种子蛋白(50μg)之蛋白质印迹。(A)Apo40为pha-PRS-D9 scFv-klip8-Apo AI原。(B)Apo41为pha-PRS-D9 scFv-klip8-Apo AI(+met)。c24种子蛋白(50μg)用做阴性对照，而0.5μg人血清白蛋白用做阳性对照。
图33是使用多克隆Apo AI抗体的总种子蛋白(50μg)之蛋白质印迹。(A)Apo42为pha-PRS-D9 scFv-klip8-Apo AI原(+met)。c24种子蛋白(50μg)用做阴性对照，而0.5μg人血清白蛋白用做阳性对照。
图34是使用多克隆Apo AI抗体的总种子蛋白(50μg)之蛋白质印迹。(A)Apo44为pha-PRS-D9 scFv-klip8-Apo AI原-KDEL。(B)Apo45为pha-PRS-D9 scFv-klip8-mat-Apo AI(+met)。c24种子蛋白(50μg)用做阴性对照，而0.5μg人血清白蛋白用做阳性对照。
图35是使用多克隆Apo AI抗体的总种子蛋白(50μg)之蛋白质印迹。(A)Apo46为pha-PRS-D9 scFv-klip8-Apo AI原(+met)-KDEL。c24种子蛋白(50μg)用做阴性对照，而0.5μg人血清白蛋白用做阳性对照。
图36是检验与种子特异性细胞级份结合的未导向和油体导向ApoAI-GFP。使用多克隆Apo AI抗体以及从水相(AQ)级份分离的大约等量总蛋白(50μg)、油体之磷酸盐(PW)和尿素(UW)洗液(分别为PO和UO，大约20μg的作用总油体)，以及取自成熟种子的微粒体(ER)级份，进行蛋白质印迹分析。免疫印迹的Ponceau-S染色，显示加载于凝胶上之相对蛋白量(上半图)。人血清(0.5μg)用做Apo AI表达之阳性对照。(A)Apo10为Apo AI-GFP。Apo11为Apo AI原-GFP。(B)Apo12为油质蛋白-Apo AI-GFP，而Apo13为油质蛋白-Apo AI原-GFP。
图37是检验与来自种子的特异性细胞级份结合的分泌原型和成熟型Apo AI-GFP。使用抗Apo AI抗体以及从水相(AQ)级份分离的大约等量总蛋白(50μg)、油体的磷酸盐(PW)和尿素(UW)洗液(PO和UO分别大约20μg的总油体蛋白)，以及取自成熟种子的微粒体(ER)级份，进行蛋白质印迹分析。免疫印迹的Ponceau-S染色，显示加载于凝胶上之相对蛋白量(上半图)。人血清(0.5μg)用做Apo AI表达的阳性对照。Apo15为PRS-Apo AI-GFP。Apo16为PRS-Apo AI原-GFP。
图38是叶内Apo AI-GFP翻译融合构建体之组成型表达。使用抗GFP抗体以及从叶分离的大约等量总蛋白(50μg)进行蛋白质印迹分析。免疫印迹之Ponceau-S染色，表示加载于凝胶上之相对蛋白量(上半图)。野生型(c24)植物用做GFP表达的阴性对照。纯化GFP蛋白(200ng)用做GFP之阳性对照。包含UG-14和UR2作为叶中累积的GFP蛋白之阳性对照。预期质量如下Apo17＝55.4kDa；Apo18＝56.4kDa；Apo19＝58.3kDa；Apo20＝59.3kDa；UG-14＝26.8kDa；UR2＝50kDa。
图39是种子内未导向而分泌的Apo AI的种子特异性表达。使用抗Apo AI抗体以及从成型种子分离的大约等量总蛋白(50μg)进行蛋白质印迹分析。免疫印迹之Ponceau-S染色，表示加载于凝胶上之相对蛋白量(上半图)。野生型(c24)植物用做Apo AI表达的阴性对照。人血清(0.5μg)用做Apo AI表达的阳性对照。预期质量如下Apo21＝28.3kDa；Apo22＝29.32kDa；Apo23＝46.9kDa；Apo24＝47.8kDa；Apo25＝51.5kDa；Apo26＝52.5kDa；Apo27＝51.3kDa；Apo28＝52.3kDa；Apo29＝31.3kDa；Apo30＝32.2kDa。
图40是检验Apo22-3(未导向Apo AI原)T3世代种子之亚细胞级份。使用抗Apo AI抗体以及从水相(AQ)级份分离的大约等量总蛋白(50μg)、取自成熟种子的油体之磷酸盐(PW)和尿素(UW)洗液(PO和UO，分别大约20μg的所用总油体)。免疫印迹之Ponceau-S染色显示凝胶上所加载相对蛋白量(上半图)。人血清(0.5μg)用做ApoAI表达之阳性对照。分子量大小列在左侧。
图41是以尼罗红染色的后期子叶阶段胚细胞内所表达Apo AI-GFP种子特异性构建体之共聚焦显微照片。(A-C)Apo10为融合于GFP的未导向成熟Apo AI。(D-F)Apo11为融合于GFP的未导向Apo AI原。(G-I)Apo12为融合于GFP的成熟Apo AI，使用油质蛋白导向油体。(1栏)绿波道。(2栏)红波道。(3栏)合并波道。条线＝5μm。
图42是以尼罗红染色的后期子叶阶段胚细胞内所表达Apo AI-GFP种子特异性构建体之共聚焦显微照片。(A-C)Apo13为融合于GFP的Apo AI原，使用油质蛋白导向油体。(D-F)Apo15为融合于GFP的成熟Apo AI，导向分泌通路。(G-I)Apo16为融合于GFP的Apo AI原，导向分泌通路。(1栏)绿波道。(2栏)红波道。(3栏)合并波道。条线＝5μm。
图43是以尼罗红染色的后期子叶阶段胚细胞内组成型表达未导向而分泌Apo AI-GFP融合蛋白之共聚焦显微照片。(A-C)Apo17为融合于GFP之未导向成熟Apo AI。(D-F)Apo18为融合于GFP的未导向Apo AI原。(G-H)Apo19为融合于GFP之成熟Apo AI，导向分泌通路。(J-L)Apo20为融合于GFP之Apo AI原，导向分泌通路。(1栏)绿波道。(2栏)红波道。(3栏)合并波道。条线＝5μm。
图44是在叶表皮细胞内所表达Apo AI-GFP组成型构建体之共聚焦显微照片。(A-C)Apo17为融合于GFP的未导向成熟Apo AI。(D-F)Apo18为融合于GFP之未导向Apo AI原。(G-H)Apo19为融合于GFP之成熟Apo AI，导向分泌通路。(J-L)Apo20为融合于GFP之Apo AI原，导向分泌通路。(1栏)绿波道。(2栏)红波道。(3栏)合并波道。条线＝5μm。
图45是Apo25，Apo26和Apo28利用反相层析法纯化。(A)Apo AI标准之HPLC痕迹。(B)Apo25之HPLC痕迹。(C)Apo26之HPLC痕迹。(D)Apo28之HPLC痕迹。所用个别波长包含214,254,280和326nm。
实施方式如上所述，本发明涉及在转基因植物内生产载脂蛋白之方法。本发明意外发现在植物内生产载脂蛋白之方法，不但可行，而且明显优于常规方法。以植物为基本的生产原料更为稳定，尤其是在植物种子内生产蛋白质，而且无细菌内毒素。因此，本发明提供生产载脂蛋白的安全源料。又发现载脂蛋白的重组体表达可产生天然载脂蛋白，其差不多是纯的形式，其水平可供商业化规模生产载脂蛋白。因此，按照本发明，提供了在植物内表达编码载脂蛋白的核酸序列之方法，包括(a)提供嵌合核酸构建体，其包括在5’至3’转录方向可操作连接的下列成份(i)能够控制在植物细胞内表达之核酸序列；和(ii)编码载脂蛋白多肽之核酸序列；
(b)把嵌合核酸构建体导入植物细胞内；以及(c)让植物细胞成长为表达载脂蛋白之成熟植物。
本发明人等发现通过在植物种子内表达重组体蛋白质，即可达成的载脂蛋白高水平表达。因此，本发明提供在植物种子内表达方法，包括(a)提供嵌合核酸构建体，其包括在5’至3’转录方向可操作连接的下列成份(i)能够控制在植物种子细胞内表达之核酸序列；和(ii)编码载脂蛋白多肽之核酸序列；(b)把嵌合核酸构建体导入植物细胞内；以及(c)让植物细胞成长为能够结籽的成熟植物，其中种子表达载脂蛋白。
术语和定义除非另有指明，否则本案所用技术和科学术语，与本发明所属领域的技术人员常用的意义相同。所有专利、专利申请、公告和其它出版物，包括来自GenBank、SwissPro和其它参照数据库之核酸和多肽序列者，均全文列此作为参考。
所用术语“核酸序列”指核苷或核苷酸的单体的序列，由天然存在的碱、糖和糖间(骨架)连键组成。此术语亦包含修饰或取代序列，包括非天然存在的单体或其部份。本发明核酸序列可为脱氧核糖核酸序列(DNA)或核糖核酸序列(RNA)，并可含有天然存在的碱基，包含腺嘌呤、鸟苷酸、胞嘧啶、胸腺嘧啶、和尿嘧啶。序列还可含有修饰的碱基，这些修饰的碱基的实例例如为“氮(aza)”和“脱氮(deaza)”腺嘌呤、鸟苷酸、胞嘧啶、胸腺嘧啶和尿嘧啶，以及黄嘌呤和次黄嘌呤。
术语“编码载脂蛋白之核酸序列”和“编码载脂蛋白多肽之核酸序列”，可互换使用，指编码载脂蛋白多肽的任何和全部核酸序列，包含任何哺乳动物载脂蛋白多肽，以及编码载脂蛋白原和前载脂蛋白原之任何核酸序列。于此所称“载脂蛋白原”指含有翻译后被裂解的多肽之载脂蛋白多肽，在天然的人体载脂蛋白中，肽原是6个氨基酸残基多肽链。术语“前载脂蛋白原”指载脂蛋白原分子，另外包括N-末端信号序列，方便多肽链的细胞内转运。编码载脂蛋白多肽的核酸序列，又含有任何和全部核酸序列，后者(i)编码与上述载脂蛋白多肽序列基本上相同的多肽；(ii)在至少中度严格的杂交条件下，与上述任何载脂蛋白核酸序列杂交，或在至少中度严格条件下会对其杂交，如果不是使用同义密码子的话。
术语“基本上相同”意指二个多肽序列以至少70％相同为优选，以至少85％相同更优选，又以至少95％相同最优选，可例如96％、97％、98％或99％相同。为测定二多肽序列间相同的百分比，使用例如Needleman和Wunsch的比对方法(J.Mol.Biol.，1970，48443)，经Smith和Waterman修正(Adv.Appl.Math.，1981，2482)，将如此二序列之氨基酸序列加以比对，使二序列间可得最高阶匹配，而在二序列间测得相同的氨基酸数。二氨基酸序列间一定百分比之计算方法为本领域所认知，包含例如Carillo和Lipton所载(SIAM J.Applied Math.，1988，481073)，以及《计算分子生物学》所载(Lesk编，1988年纽约市牛津大学出版部，生物计划讯息学和基因组计划案)。一般而言，如此计算可以采用计算机程序。可用于此方面之计算机程序，包含但不限于GCG(Devereux等人，Nucleic Acids Res.，1984，12387)BLASTP、BLASTIN和FASTA(Altschul等人，J.Molec.Biol.，1990215403)。二多肽间相同百分比之特别优选的测定方法，涉及W.Clustal演算(JDThompson，DG Higgines和TJ Gibson，1994，Nucleic Acid Res.，22(22)4673-4680)，以及BLOSUM 62评分矩阵(S Henikoff & JG Henikoff，1992年，Proc.Natl.Acad.Sci.USA 8910915-10919)，使用间隙开口处分10和间隙延伸处分0.1，使二序列间得最高阶匹配，在比对中涉及二序列之一的总长度至少50％。
“至少中等严格杂交条件”意指选定的条件，促进二互补核酸分子间在溶液内的选择性杂交。杂交可发生在核酸序列分子的全部或一部份。杂交部份典型上长度为至少15个(例如20、25、30、40或50个)核苷酸。凡本领域人员均知，核酸双链体或杂种之稳定性，是由Tm决定，其在含钠的缓冲液内，是钠离子浓度和温度的函数(Tm＝81.5℃-16.6(Log10〔Na+〕)+0.41(％(G+C)-600/1)，或类似方程式)。因此，决定杂种稳性的洗液条件内之参数，是钠离子浓度和温度。为检定对已知核酸分子相似但非相同的分子，假定1％错配，造成Tm降低约1℃，例如找到＞95％相同的核酸分子，则最后洗液温度降低约5℃。基于如此考量，凡本领域人员均能轻易选择适当的杂交条件。在优选的实施方式中，选用严格的杂交条件。举例而言，可采用下述条件，以达成严格杂交以5×氯化钠/柠檬酸钠(SSC)/5×Denhardt’s溶液/1.0％SDS，在Tm(根据上式)-5℃，接着以洗液0.2×SSC/0.1％SDS，在60℃杂交。中度严格杂交条件包含以3×SSC在42℃的洗涤步骤。然而，须知使用其他缓冲液、盐和温度，亦可达成等效严格性。有关杂交条件之另外指引，可参见《分子生物学之目前方案》(John Wiley & Sons，N.Y.1989，6.3.1-6.3.6)和Sambrook等人《分子克隆实验手册》(冷泉港实验室出版社，1989，第3卷)。
于此所称“载脂蛋白”和“载脂蛋白多肽”，指载脂蛋白的任何和全部多肽序列，包含全部哺乳动物载脂蛋白多肽，和包括氨基酸残基序列之多肽，后者是(i)基本上与上述构成任何载脂蛋白多肽的氨基酸序列相同，或(ii)利用核酸序列编码，能够在至少中度严格条件下，杂交于上述编码载脂蛋白的任何核酸序列，或能够在至少中度严格条件下，杂交于上述编码载脂蛋白的任何核酸序列，如果不是使用同义密码子的话。“载脂蛋白”和“载脂蛋白多肽”包含载脂蛋白原多肽在内。载脂蛋白多肽以人、猪或牛来源为优选。在优选的实施方式中，此等载脂蛋白包含但不限于载脂蛋白A-I(Apo AI)、载脂蛋白A-IV(Apo AIV)、载脂蛋白A-V(Apo AV)和载脂蛋白E(Apo E)。
术语“嵌合”就核酸序列而言，指至少2个连接的核酸序列，所述核酸序列在天然条件下是不连接的。嵌合核酸序列包含不同天然来源之连接的核酸序列，例如构成植物启动子的核酸序列连接于编码人载脂蛋白的核酸序列，可视为嵌合。嵌合核酸序列亦可包含同样天然来源的核酸序列，条件是它们不是天然连接的。例如构成由特殊细胞类型所得启动子的核酸序列，可连接于编码来自同样细胞类型的多肽之核酸序列，但后者通常不连接于构成启动子之核酸序列。嵌合核酸序列亦包含这样的核酸序列，其包括连接于任何非天然存在之核酸序列的任何天然存在的核酸序列。
制备重组表达载体，其包括编码载脂蛋白之嵌合核酸序列以及能够控制在植物细胞内的表达之核酸序列可用于本发明的方法和组合物的编码载脂蛋白之核酸序列，可为编码载脂蛋白多肽之任何核酸序列，包含任何载脂蛋白原和前载脂蛋白原。
人体血浆内发现许多不同的载脂蛋白，有信号的作用，造成脂蛋白作用于某些组织，或活化作用于此类脂蛋白之酶(A.Lehninger等人《生物化学原理》第二版，纽约，Worth出版公司，1993年)。此等蛋白质包含但不限于下列载脂蛋白之等位基因和异构体，例如Apo AI(例如参见CR Sharpe等人，Nucleic Acids Res.12(9)，3917-3932(1984))、Apo II(例如参见CR Sharpe等人，Nucleic Acids Res.12(9)，3917-3932(1984))、Apo IV(例如参见NA Elshourbagy等人，J.Biol.Chem.261(5)，1998-2002(1986))、Apo AV(例如参见Hubacek等人，Physiol.Res.2004，53225-228)、Apo B-100(例如参见SW Law等人，Proc.Natl.Acad.Sci.USA，83(21)，8142-8146(1986))、Apo B-48(例如参见LMPowell等人，Cell 50(6)，831-840(1987))、Apo C-II(例如参见CRSharpe等人，Nucleic Acids Res.12(9)，3917-3932(1984))、Apo C-III(例如参见CR Sharpe等人，Nucleic Acids Res.12(9)，3917-3932(1984))、Apo C-IV(例如参见CM Allan等人，Genomics 28(2)，291-300(1995))、Apo D(D.Drayna等人，J.Biol.Chem.261(35)，16535-16539(1986))、Apo E(例如参见JL Brewslow等人，J.Biol.Chem.257(24)，14639-14641(1982))、Apo F(例如参见JR Day等人，Biochem.Biophys.Res.Commun.203(2)，1146-1151(1994))、Apo H(例如参见H.Mehdi，Gene 108(2)，293-298(1991))，以及Apo L(例如参见P.N.Duchateau等人，J.Biol.Chem.272(41)，25576-25582(1997))。编码载脂蛋白之核酸序的实例，在本领域已属公知，一般由各种各样哺乳动物源轻易可得，包含人类(见上述)、猪(例如参见VN Trieu等人，Gene 134(2)，267-270(1993))、牛(例如参见Y.W.Yang等人，J.Mol.Evol.32(6)，469-475(1991))、羊(例如参见J.A.Robertson等人，J.Steroid Biochem.Mol.Biol.67(4)，285-292(1998))等。可用于编码人载脂蛋白之序列，包含编号SEQ ID NO1、7和8所示的多肽链的序列，而按照本发明可用于编码非人类载脂蛋白之序列，如SEQ ID NO9-55和241-251所示。编码载脂蛋白多肽链之各相对应核酸序列，经由表1中所提供识别号码，即可轻易鉴定。使用此等核酸序列，以本领域人员熟知之技术，即可轻易鉴定编码其他的新的载脂蛋白之核酸序列。例如表达文库、cDNA和基因组文库等等文库，均可筛选，而含有来自排列计划的序列信息的数据库，可以查寻类似序列。编码载脂蛋白多肽的另外核酸序列，可用其他方法加以分离，而按照本发明，可发现和使用新的序列。在优选的实施方式中，编码载脂蛋白之核酸序列，是人类、猪和牛的载脂蛋白。
许多载脂蛋白类似物为现有技术所知(例如参见MC Cheung等人，Biochim Biophys Acta.1988年5月2日；960(1)73-82，和W.Strobl等人，Pediatr Res.1988年8月；24(2)222-8)，且可按照本发明使用。于此可用之类似物包含人体载脂蛋白分子，其中发现各种天然和合成突变和修饰，包含但不限于点突变、缺失突变、移码突变和化学修饰。按照本发明优选的实施方式，使用称为Apo AI-M之天然变体，按照本发明可用之突变和修饰例，包含但不限于表2所列。
在优选的实施方式中，所用的编码载脂蛋白的核酸序列是载脂蛋白原。
编码载脂蛋白的核酸序列，加以变更以制造载脂蛋白类似物，可用本领域人员所知的各种核酸修饰技术为之，包含例如定点诱变、定向诱变、随机诱变、添加有机溶剂、基因倒位，或与本领域人员所知其它技术组合(Shraishi等人，1988，Arch.Biochim.Biophys，358104-115；Galkin等人，1997，Protein Eng.10687-690；Carugo等人，1997，Proteins2810-28；Hurley等人，1996，Biochem，355670-5678；Holmberg等人，1999，Protein Eng.12851-856)。
按照此，编码载脂蛋白的核酸序列，连接于能够控制在植物细胞内表达载脂蛋白多肽之核酸序列。因此，本发明亦提供编码载脂蛋白之核酸序列，其连接于能够控制在植物细胞内表达之启动子。此处可用的能够控制在植物细胞内表达的核酸序列，包括能够控制在植物内表达多肽之任何植物所衍生启动子。一般而言，若按照此选择双子叶植物，则可用双子叶植物品种所得启动子，而选择单子叶植物品种时，可用单子叶植物启动子。在一实施方式中，使用启动子导致在全株植物内表达载脂蛋白多肽。可用之组成型启动子，包含例如35S花椰菜镶嵌病毒(CaMV)启动子(Rothstein等人，1987，Gene 53153-161)、水稻肌动蛋白启动子(McElroy等人，1990，Plant Cell 2163-171；美国专利6,429,357号)、遍在蛋白启动子，例如玉米遍在蛋白启动子(美国专利5,879,903和5,273,894号)以及荷兰芹遍在蛋白启动子(P.Kawalleck等人，1993，Plant Mol.Biol.21673-684)。
在本发明特别优选的实施方式中，于植物种子内生成载脂蛋白。在植物种子内生成具有把载脂蛋白作为原料储存和运输的弹性，因为载脂蛋白从储存种子提取时保有其活性。此外，需经提取的生物量有限，由于植物种子内存在的水含量较低。因此，在本发明优选的实施方式中，植物细胞是种子细胞，而植物成长为能够结籽之成熟植物，其中种子表达载脂蛋白。在又一优选的实施方式中，能够控制在植物细胞内表达的核酸序列是种子优选之启动子，例如菜豆蛋白启动子。在如此实施方式中，使用启动子造成载脂蛋白多肽优先表达在种子组织内。“种子优先启动子”指控制表达重组蛋白(即载脂蛋白)之启动子，使成熟植物内存在的重组蛋白总量优选地至少80％存在于种子内。优选地是成熟植物内存在的重组蛋白总量至少95％存在于种子内。在此方面可用之种子优先启动子，包括例如大豆菜豆蛋白启动子(Sengupta-Gopalan等人，1985，Proc.Natl.Acad.Sci.USA 823320-3324)；拟南芥18kDa油质蛋白启动子(美国专利5,792,922号)或亚麻油质蛋白启动子(WO 01/16340号)；或亚麻豆球蛋白般种子储蛋白(核丝)启动子(WO 01/16340号)；亚麻2S储存蛋白启动子(WO 01/16340号)；胚乳优先启动子，例如Amy32b启动子(Rogers和Milliman，J.Biol.Chem.，1984，25912234-12240)、Amy6-4启动子(Kursheed和Rogers，J.Biol.Chem.，1988，26318953-18960)，或Aleurain启动子(Whittier等人，1982，NucleicAcids Res.，152515-2535)，或大豆arcelin启动子(GD Jaeger等人，2002，Nat.Biotechnol，Dec；201265-8)。各种植物内可用之新启动子持续被发现。植物启动子有许多例可参见Ohamuro等人(Biochem.ofPlants.，1989，151-82)。
在本发明优选的实施方式中，嵌合核酸序列还包括编码稳定多肽之核酸序列，其符合读框地连接于编码载脂蛋白之核酸序列。稳定多肽用于方便蛋白质折叠和/或增进载脂蛋白稳定累积于植物细胞内。此外，稳定多肽可用来把载脂蛋白导向植物细胞内所需位置，和/或方便载脂蛋白之纯化。稳定多肽以在无载脂蛋白存在下，可轻易表达和稳定累积在转基因植物细胞内之多肽为优选。稳定多肽可为植物特异性型或非植物特异性型多肽。按照本发明可用之植物特异性稳定多肽，包含油体蛋白(见下述)和硫氧化还原酶，例如在SEQ ID NO56内所示硫氧化还原酶。按照此可用之非植物特异性稳定多肽，包含绿色荧光蛋白(GFP)(Davis和Vierstra，1996，Weeds World 3(2)43-48)(SEQ ID NO57)，及其单链抗体或片段。非植物特异性稳定多肽优选地经密码子最佳化，以便在植物内有最佳表达。
单链抗体或在此优选使用之抗体，包含方便载脂蛋白纯化之单链抗体或其片段。按照此，可用例如能够与油体或油体蛋白特异性结合之单链抗体或其片段，因而容许载脂蛋白与从植物种子轻易可得之油体级份共同纯化。单链抗体以能够与从表达载脂蛋白的种子所得油体蛋白相结合为优选，即在使用拟南芥植物细胞的本发明实施方式中，选用单链抗体或其片段，能够与拟南芥油体蛋白相结合。在又一优选的实施方式中，单链抗体是能够与来自拟南芥(Arabidopsis thaliana，D9scFv)的18kDa油质蛋白特异性结合之单链FV抗体。在最佳实施方式中，单链抗体如SEQ ID NO240所示。于此所用术语“单链抗体片段”(scFv)或“抗体片段”，指多肽含有各种可变轻(VL)结构域，利用肽接头(L)连接于可变重(VH)结构域，以VL-L-VH表示。“结构域(domain)”是承担分别功能的蛋白质区段，例如抗原结合或抗原识别。本发明内所用单链抗原片段，可从任何抗体的轻和/或重链可变结构域衍生。轻、重链可变结构域以同样抗原特异性为优选。优选的抗原是油体蛋白，结合形成多价单链抗体的个别抗体片段，可针对同样抗原或不同抗原引导。产生单链抗体的方法为技术上所公知。例如单链抗体可利用筛选单链(scFV)噬菌体展示文库所产生。
从噬菌体展示文库产生单链抗体的方法，在技术上已属公知。McCarrerty等人(Nature 348552-554)证明使用噬菌体显示系统中，抗体的片段表达成具有fd噬菌体载体之融合蛋白，得以在噬菌体表面表达单链抗体。使用例如由Amersham生物科技学和Cambridge抗体科技所开发的重组噬菌体抗体系统，可达成单链抗体噬菌展示文库之生产。更详细方案可从Amersham生物科技获得，分3部份销售，包含小鼠scFV分子、表达模块和检测模块。简言之，单链抗体的生产方案如下。从所研究抗原免疫接种过的小鼠所得小鼠杂交瘤或小鼠脾细胞，可得信使RNA。小鼠杂交瘤代表待克隆的抗体基因最丰富来源，因其表达单一抗体用的重、轻链基因，但抗体亦可使用来自免疫接种小鼠的脾细胞加以克隆。使用逆转录酶和随机六聚体引物，可将mRNA转换成cDNA。使用随机六聚体可得cDNA分子，长度足以克隆重、轻链分子的可变区。俟产生cDNA分子后，即进行主要PCR反应，分开扩增重、轻可变区。引物的设计在于利用链两端杂交，将重或轻链可变区扩增。可变区一旦扩增PCR反应即受到琼脂糖凝胶电泳和凝胶纯化，以除去引物和任何外部PCR产物。重、轻链可变区一旦纯化，即可用接头组合为单一基因。接头区的设计在于确保重、轻链间维持正确读框。例如可变重链(VH)和可变轻链(VL)可用(Gly4Ser)3接头连接，而得长度大约750碱基对之单链抗体片段(scFv)。一旦重、轻链与接头组合，即进行次级PCR反应，将组合的scFV DNA片段扩增。引物应设计成引进限制位点，容许克隆成噬菌体粒表达载体。例如SfiI和NotI位点可加到此等scFv基因的5’和3’末端，供克隆成pCANTAB 5E载体(Amersham生物科学)。一旦PCR完成，DNA片段应纯化，以除去未加入之引物和dNTPs。此可用回旋管柱纯化达成。DNA片段一旦已告纯化和量化，片段即以适当限制性酶消化，使克隆成适当表达载体。DNA片段随即连结于表达载体，例如pCANTAB 5E(Amersham生物科学)，并导入胜任大肠杆菌细胞内。细胞应在适当选用培养基上成长，确保只有含表达载体的细胞会成长(即使用特殊碳源和抗生素选择)。大肠杆菌一旦成长，含噬菌体粒之菌落，即以M13辅助噬菌体(即KO7-Amersham生物科学)感染，生成重组噬菌体，显示scFv片段。M13噬菌体会发动噬菌体复制，产生完整噬菌体颗粒，从细胞释出，在表面表达scFv物种。显示正确scFv抗体的噬菌体，可通过晃动使用特殊抗原来检定。为消除非特异性噬菌体，可把重组噬菌体的培养物转移到涂布抗原之支持体(即烧瓶或试管)，加以洗涤。只有显示正确scFv的噬菌体会结合于支持体。易感的大肠杆菌菌株随即以结合于涂布抗原的支持体之噬菌体加以感染。噬菌体可通过辅助噬菌体的抢救而富集，并对抗原晃动多次，亦可直接平板接种于固体培养基上，不需进一步富集。以对适当抗原选用的噬菌体感染过的大肠杆菌细胞，经平板接种，而拾取个别菌落。取自个别菌落的噬菌体，再使用例如ELISA检验法(酶联免疫吸附试验)加以检验。使用ELISA检验为阳性之噬菌体抗体，即可用来感染大肠杆菌HB2151细胞，以供生产可溶性重组抗体。适当克隆一旦选定，即可检定scFv抗体基因之序列，用于本发明。
稳定蛋白可经由接头连接于载脂蛋白，可裂解以释出游离天然型之载脂蛋白。可包含在此方面内之接头，包含以Xa因子、IgA蛋白酶或肠激酶识别之肽序列。在特别优选的实施方式中，接头编码凝乳酶前序列，可通过成熟的凝乳酶分解，见PCT专利申请WO 98/49326号。
在优选的实施方式中，嵌合核酸序列还包括“导向信号”。于此所用导向信号意指能够把载脂蛋白多肽在表达时引导至植物细胞内所需位置之任何氨基酸序列。于此可用之适当导向信号，包含能够把载脂蛋白多肽导向内质网状体，或衍自内质网状体的贮存小泡，例如油体，以及质外体。
为达成载脂蛋白累积于ER或ER衍生的贮存小泡，编码载脂蛋白之多肽连接于导向信号，造成载脂蛋白保存在ER或ER衍生之贮存小泡内。在本发明优选的实施方式中，能够把载脂蛋白保存在ER内之导向信号，含有羧基末端ER-保留基序。此等羧基末端ER-保留基序包含KDEL、HDEL、DDEL、ADEL和SDEL序列。其它例包含HDEF(Lohmann等人，2001，Plant Physiol，127(2)436-439)，或二精氨酸，接近位于2和3、3和4或4和5位置之氨基末端(摘自Plant Biology2001 Program，ASPB，2001年7月，美国罗得岛州Providence市)。编码羧基末端保留基序的核酸序列，宜连接到编码载脂蛋白的核酸序列，其方式使能够将载脂蛋白保存在ER内之多肽，即连接于载脂多肽的羧基末端。
在将载脂蛋白保存在ER内之本发明实施方式中，嵌合核酸序列另含有核酸序列，把核酸序列导向内膜系统(“信号肽”)。在载脂蛋白多肽使用KDEL、HDEL或SDEL多肽等序列保存在ER内之本发明实施方式中，特别需要含有编码信号肽之核酸序列。于此可用之信号肽例，包含烟草发病相关蛋白(PR-S)信号序列(SEQ ID NO58)(Sijmons等人，1990，Bio/technology，8217-221)、卵磷脂信号序列(Boehm等人，2000，Transgenic Res.9(6)477-86)、来自菜豆(Phaseolus vulgaris)富含羟基脯胺酸的糖蛋白之信号序列(Yan等人，1997，Plant Phyiol，115(3)915-24和Corbin等人，1987，Mol Cell Biol 7(12)4337-44)、马铃薯patatin信号序列(G.Iturriaga等人，1989，Plant Cell 1381-390和Bevan等人，1986，Nuc.Acids Res.414625-4638)，以及大麦α-淀粉酶信号序列(Rasmussen和Johansson，1992，Plant Mol.Biol.18(2)423-7)。于此实施例3表示载脂蛋白累积于ER内。
在又一优选的实施方式内，载脂蛋白多肽是连接于能够将载脂蛋白多肽保存在ER衍生贮存小泡内之多肽。在优选的实施方式中，ER衍生贮存小泡为油体，而载脂蛋白连接于油体蛋白。在此方面可用之油体蛋白包含与油体天然相关之任何蛋白(见表3内SEQ ID NO59-137)。编码油体蛋白多肽链之各相对应核酸序列，经由表3提供之识别符号码，可轻易检定，使用此等核酸序列，以本领域人员所知技术，即可轻易检定编码其他新的油体蛋白的核酸序列，例如可筛选表达库、cDNA和基因组库等，并可为类似序列，从测序计划查索含序列信息之数据库。可用其他方法，以分离编码油体蛋白多肽链的另外核酸序列，并按照本发明发现和使用新的序列。特别优选的油体蛋白是油质蛋白，例如玉米油质蛋白(Bowman-Vance等人，1987，J.Biol.Chem.26211275-11279；Qu等人，1990，J.Biol.Chem.2652238-2243)或油菜类(Lee等人，1991，Plant Physiol，961395-1397)、caleosin(例如参见Genbank编目AF067857号)，以及steroleosins(Lin等人，2002，Plant Physiol，128(4)1200-11)。在进一步优选的实施方式中，油体蛋白为植物油质蛋白，与其它植物油质蛋白，例如从拟南芥(Arabidopsis thaliana，SEQID NO138)或油菜(Brassica napus，SEQ ID NO139)分离之油质蛋白。在另一实施方式内，油体蛋白是来自植物、真菌或其它来源之caleosin，与例如从拟南芥(SEQ ID NO140和SEQ ID NO141)分离的caleosin等植物caleosin，享有序列同源性。在另一实施方式中，油体蛋白为steroleosin(SEQ ID NO142)(L-J Lin等人，2002，PlantPhysiol 1281200-1211)，本发明此实施方式在实施例3内举例说明。
此外，按照本发明可通过表达载脂蛋白，而将载脂蛋白导向油体，使得载脂蛋白不含导向信号，惟编码载脂蛋白之核酸序列，包括载脂蛋白肽原。本发明此实施方式参见实施例3。
能够将载脂蛋白保存在ER或ER衍生贮存小泡内之多肽，典型上不裂解，而载脂蛋白可以融合蛋白的形式累积，例如典型情况为，使用KDEL保留信号将多肽保留于ER内，或使用油体蛋白把多肽保留在油体内。
在本发明另一实施方式中，载脂蛋白多肽表达方式视，使多肽累积在质外体。为达成如此累积，嵌合核酸序列宜包括导向序列，能够将载脂蛋白多肽引导至ER(“信号肽”)，于此可用的信号肽例如包含上述烟草发病相关蛋白(PR-S)信号序列(SEQ ID NO58)(Sijmons等人，1990，Bio/technology，8217-221)、卵磷脂信号序列(Boehn等人，2000，Transgenic Res.9(6)477-86)、来自菜豆(Phaseolus vulgaris)富含羟基脯胺酸的糖蛋白之信号序列(Yan等人，1997，Plant Phyiol，115(3)915-24和Corbin等人，1987，Mol Cell Biol 7(12)4337-44)、马铃薯patatin信号序列(G.Iturriaga等人，1989，Plant Cell 1381-390和Bevan等人，1986，Nuc.Acids Res.414625-4638)，以及大麦α-淀粉酶信号序列(Rasmussen和Johansson，1992，Plant Mol.Biol.18(2)423-7)。此等导向信号可在体内从载脂蛋白分裂，典型情况为使用质外体导向信号，例如烟草发病相关蛋白S(PR-S)信号序列(Sijmons等人，1990，Bio/technology，8217-221)。其它信号肽可用SignalP World Wide Web服务站(http//www.cbs.dtu.dk/services/SignalP/)预计，可预计来自不同微生物的氨基酸序列内信号肽裂解位点之存在和位置。一般而言，主要氨基酸序列稍微保守，虽然一般物理化学性能保守到某些程度。信号肽的概括结构有三区，短氨基末端“n区”含有带正电残基，中央疏水性“h区”大小范围在7至15个氨基酸，和羧基末端“c区”含极性氨基酸，以及由膜结合信号肽酶识别之裂解部份(K.Nakai，2000，Advancesin Protein Chem 54277-344)。按照此亦可用之导向信号，包含天然载脂蛋白信号序列(以人体序列言，长度为18个氨基酸)。在其优选的实施方式中，位于氨基末端的质外体导向序列，例如前述烟草PR-S序列，可与位于羧基末端的ER保留序列，例如KDEL序列组合使用。
在又一优选的实施方式中，编码载脂蛋白的核酸序列，其表达方式是使载脂蛋白累积在细胞质内。在如此实施方式内，核酸序列不包括导向信号。在如此实施方式中，载脂蛋白包括其它稳定多肽，例如绿色荧光蛋白(GFP)。
嵌合核酸序列亦可包括氨基和/或羧基多肽延伸段。此等延伸段可用来稳定和/或协助折叠载脂蛋白多肽链，亦可方便导向细胞内之区室，例如油体。在此方面可用之多肽延伸段，包含例如编码单链抗体之核酸序列，编码绿色荧光蛋白之核酸序列(Davis和Vierstra，1996，Weeds World3(2)43-48)，或此类多肽之组合物。特别需要的单链抗体延伸段，包含可使载脂蛋白与油体结合的延伸段，以方便与油体级份结合的载脂蛋白纯化。此等延伸段宜包含在本发明实施方式内，其中载脂蛋白在植物种子内表达，并在种子细胞内导向ER或质外体。
在又一实施方式内，裂解位点可位于载脂蛋白A-I肽的氨基末端之上游，或羧基末端之下游，使得载脂蛋白A-I多肽可从融合伙伴裂解，而得分离载脂蛋白A-I。此等裂解位点之例可参见WO 98/49326(融合蛋白的裂解方法)和相关专利申请，以及La Vallie等人(1994)“融合蛋白之酶和化学裂解”，载于《分子生物学的当前方案》第16.4.5-16.4.17页，John Wiley & Sons，Inc.纽约。在优选的实施方式中，裂解位点是KLIP 8(SEQ ID NO143)，可利用含凝乳酶的天冬胺酸蛋白酶加以裂解。在又一优选的实施方式中，于Apo AI多肽或Apo AI多肽原之氨基末端，加额外甲硫氨酸残基。
本发明又提供从宿主细胞成份分离异源蛋白之方法，是把油体级份隔离，随即经由异源蛋白-油体蛋白融合之特殊裂解，而释放异源蛋白。视情形，裂解位点可在异源多肽的氨基末端上游和羧基末端下游，使得融合多肽可通过分相而裂解和分离成其组份肽。
编码载脂蛋白之核酸序列，可加以改变以改进表达水平，例如对为表达载脂蛋白多肽而选用的特定植物细胞类型，按照优选的密码子使用，优化核酸序列，或改变将mRNA去稳定化所知基序(例如参见PCT专利申请97/02352号)。编码载脂蛋白多肽的核酸序列之密码子使用，与植物细胞型的密码子使用加以比较，使密码子的识别可以改变。利用改变密码子使用构建合成基因，载于例如PCT专利申请93/07278号。
在优选的实施方式中，所用编码载脂蛋白的核酸序列，以SEQ IDNO.1、SEQ ID NO.3或SEQ ID NO.5表示。
在此可用一些遗传元件，能够增进载脂蛋白多肽之表达。此等元件包含从某些病素未翻译之前导序列，例如AMV前导序列(Jobling和Gehrke，1987，Nature，325622-625)，以及与玉米遍在蛋白启动子关联之内含子(美国专利5,504,200号)。一般而言，可制备嵌合核酸序列，使能够增进表达的遗传元件位于编码载脂蛋白多肽的核酸序列之5’。
按照本发明，包括能够控制在植物内表达的启动子之嵌合核酸序列，其连接于编码载脂蛋白多肽之核酸序列，可掺入重组表达载体，其确保在细胞内有良好表达。因此，本发明包含重组表达载体，其包括在5’至3’的转录方向可操作连接的下列成份(i)能够控制在植物细胞内表达之核酸序列；和(ii)编码载脂蛋白多肽之核酸序列；其中表达载体适于在植物细胞内表达。“适于在植物细胞内表达”指重组表达载体包括本发明嵌合核酸序列，连接于需在植物细胞内达成表达之遗传元件。在此方面可包含在表达载体内之遗传元件，包含转录末端区，编码标志基因之一或多个核酸序列，一或多个之复制起源等等。在优选的实施方式中，表达载体还包括载体或其一部份在植物细胞核基因组内整合所需遗传元件，例如T-DNA左、右边界序列，方便在植物细胞使用土壤杆菌(Agrobacterium)转化的本发明实施方式中，整合于植物核基因组内。在又一优选的实施方式中，该植物细胞是植物种子细胞。
如前所述，重组表达载体一般包括转录终止子，除了作为转录终止信号外，又可作为能够延长mRNA半生期之保护性元件(Guarneros等人，1982，Proc.Natl.Acad.Sci.USA，79238-242)。转录终止子一般约200个核苷酸至约1000核苷酸，并制备表达载体使转录终止子位在编码载脂蛋白的核酸序列之3’。于此可用之终止序列包含例如胭脂碱终止区(Bevan等人，1983，Nucl.Acids.Res.，11369-385)、菜豆蛋白终止子(van der Geest等人，1994，Plant J.6413-423)、arcelin终止子(GDJaeger等人，2002，Nat.Biotechnol.201265-8)、根癌土壤杆菌(Agrobacterium tumefaciens)的章鱼碱合酶基因用之终止子，或其它类似功能性元件。转录终止子可按An所述获得(An，1987，Methods inEnzym，153292)。
根据本发明，表达载体可又含有标志基因。按照本发明可用的标志基因，包含可把转化的细胞与未转化的细胞分辨之所有基因，包含全部可选择和可筛选的标志基因。标志基因可为抵抗性标志，例如对卡那霉素(美国专利6,174,724号)、氨苄青霉素、G418、博莱霉素、潮霉素之抗生素抵抗性标志，得以利用化学手段或对化学剂耐受标志，例如正常植物毒性糖甘露糖(Negrotto等人，2000，Plant Cell Rep.，19798-803)，选择性状。于此可用之其它适宜标志，包含输送对除草剂，例如草甘膦(glyphosate)(美国专利4,940,935和5,188,642号)、草铵膦(phosphinothricin)(美国专利5,879,903号)或磺酰脲(美国专利5,633,437号)，具有抵抗性之标志，抵抗性标志连接很近编码载脂蛋白多肽之核酸序列时，可用来维持对植物细胞群体，或未丧失编码载脂蛋白多肽的核酸序列之植物，有选择性压力。可用来通过视觉检查以检定转化体之筛选型标志，包含β-葡糖酶(GUS)(美国专利5,268,463和5,599,670号)，和绿色荧光蛋白(GFP)(Niedz等人，1995，Plant CellRep.，14403)。
适于将核酸序列导入植物内用之重组载体，包含土壤杆菌和根癌菌为基本之载体，例如Ti和Ri质粒，包含例如pBIN19(Bevan，Nucl.Acid.Res.，1984，228711-8721)、pGKB5(Bouchez等人，1993，C RAcad.Sci.Paris，Life Science，3161188-1193)、双载体之pCGN序列(McBride和Summerfelt，1990，Plant Mol.Biol.，14269-276)，以及其它双载体(例如美国专利4,940,838号)。
本发明重组表达载体可按照分子生物学技术人员公知的方法制备。此项制备典型上涉及大肠杆菌的菌株，作为中间克隆宿主。大肠杆菌以及植物转化载体的制备，可用通常已知技术完成，例如限制消化、结合、凝胶电泳、DNA测序、聚合酶链反应(PCR)及其它方法。各种克隆载体都可进行制备重组表达载体所需之必要步骤。在大肠杆菌内具有复制系统功能的载体当中，有例如pBR322载体、pUC序列载体、M13mp序列载体、pBluescript等。典型上，此等克隆载体含有标志，容许选择转化细胞。核酸细胞可导入此等载体内，而载体可导入在适当培养基内成长之大肠杆菌内。重组表达载体可在细胞收获和溶菌时，从细胞回收。再者，关于制造重组载体之一般入门，可以参见例如Sambrook等人《分子克隆实验室手册》，Cold Spring Harbor实验室出版社，1989，第3卷。
制备包括能够表达载脂蛋白的种子之植物按照本发明，将嵌合核酸序列引进植物细胞内，让细胞成长为成熟植物，其中植物表达载脂蛋白多肽。
按照此，可选择任何植物品种或植物细胞。于此所用特殊细胞包含由拟南芥(Arabidopsis thaliana)、巴西坚果(Betholettia excelsa)、蓖麻豆(Riccinus communis)、椰子(Cocus nucifera)、胡荽(Coriandrumsativum)、棉(Gossypium spp.)、土豆(Arachis Hypogaea)、荷荷巴(Simmondsia chinensis)、亚麻(Linum usitatissimum)、玉蜀黍(Zeamays)、芥子(Brassica spp.和Sinapis alba)、油棕(Elaeis guineeis)、橄榄(Olea eurpaea)、油菜(Brassica spp.)、稻米(Oryza sativa)、红花(Carthamus tinctorius)、大豆(Glycine max)、番瓜(Cucurbitamaxima)、大麦(Hordeum vulgare)、小麦(Traeticum aestivum)、青浮草(Lemnaceae sp.)和葵花(Helianthus annuus)。
按照优选的实施方式，使用油籽植物之植物品种或植物细胞。于此可用的油籽植物包含花生(Arachis hypogaea)、芥子(Brassica spp.和Sinapis alba)、油菜(Brassica spp.)、蚕豆(Cicer arietinum)、大豆(Glycine max)、棉(Gossypium hirsutum)、葵花(Helianthus annuus)、(Lentil Lens culinari)、亚麻(Linum usitatissimum)、白苜蓿(Trifoliumrepens)、橄榄(Olea eurpaea)、油棕(Elaeis guineeis)、红花(Carthamus tinctorius)和narbon豆(Vicia narbonesis)。
按照优选的实施方式，使用拟南芥、亚麻或红花。
把植物重组表达载体导入植物细胞内之方法，于此亦称为“转化”，在技术上已属公知，典型上因选用的植物细胞而异。把重组表达载体导入细胞内之一般技术，包含电穿孔；化学媒介技术，例如CaCl2媒介核酸摄取；颗粒轰击(biolistics)；使用天然感染性核酸序列，例如以病毒方式衍生的核酸序列、土壤杆菌或根癌菌衍生序列、聚乙二醇(PEG)媒介核酸摄取、微注射，以及使用碳化硅晶须。
在优选的实施方式中，选用转化方法，可使嵌合核酸序列整合于植物细胞基因组内，以植物细胞核基因组为优选。按照此，被视为特别需要，乃因使用如此方法，会导致嵌合核酸序列在有性生殖时，转移至子代植物。在此方面可用之转化方法，包含颗粒轰击和土壤杆菌媒介方法。
双子叶植物品种之转化方法，已属公知。一般使用土壤杆菌媒介转化，因其效率高，且一般为许多(即使不是全部)双子叶植物品种所能感受。土壤杆菌转化一般涉及双载体，例如上述双载体之一，包括本发明嵌合核酸序列，从大肠杆菌转移到适当土壤杆菌菌株(例如EHA101和LBA4404)，利用与带有重组双载体的大肠杆菌菌株，或带有能够将双载体移动至标的土壤杆菌菌株的大肠杆菌菌株，进行之亲株匹配，或利用土壤杆菌菌株之DNA转化(Hofgen等人，Nucl.Acids.Res.，1988，169877)。可用来将双子叶植物细胞转化的其它技术，包含颗粒轰击(Sanford，1988，Trends in Biotechn.6299-302)；电穿孔(Fromm等人，1985，Proc.Natl.Acad.Sci.USA，825824-5828)；PEG媒介DNA摄取(Potrykus等人，1985，Mol.Gen.Genetics，199169-177)；微注射(Reich等人，Bio/Techn.，1986，41001-1004)；以及碳化硅晶须(Kaeppler等人，1990，Plant Cell Rep.，9415-418)，或使用例如花浸法在植物内转化(Clough和Bent，1998，Plant J.，16735-743)。
单子叶植物品种可用各种方法转化，包含颗粒轰击(Christou等人，1991，Biotechn.9957-962；Weeks等人，Plant Physiol.，1993，1021077-1084；Gordon-Kamm等人，Plant Cell，1990，25603-618)；PEG媒介DNA摄取(欧洲专利0292 435和0392 225)，或土壤杆菌媒介转化(Goto-Fumiyuki等人，1999，Nature-Biotech.17282-286)。
正确植物转化方法会因植物品种和选做转化用细胞标的之植物细胞类型而稍有变化(例如种子衍生细胞类型，像胚轴和子叶或胚组织)。如前述特别优选的实施方式，使用红花。获得红花转化体之方法，参见Baker和Dyer(Plant Cell Rep.，1996，16106-110)。另外植物品种特异性的转化方案，可查《农林生物科技46转基因作物》(Y.P.S.Bajaj编)，Springer出版社，纽约(1999)，以及《农林生物科技47转基因作物II》(Y.P.S.Bajaj编)，Springer出版社，纽约(2001)。
在转化之后，让植物细胞成长，在微分组织，例如芽和根生出时，成熟植物即告再生。典型上可再生多种植物。植物再生方法一般是有植物品种和细胞类之依赖性，为本领域人员所知。关于植物组织培养物之进一步指导，可查例如《植物细胞和组织培养物》，1994，Vasil和Thorpe编，Kluwer学术出版公司，以及《植物细胞培养物方案》(分子生物学方法111)，1999，Hall编，Humana出版社。
在一方面中，本发明提供包括载脂蛋白的植物种子获得方法。因此，本发明提供一种包括载脂蛋白的植物种子之方法，包括(a)提供嵌合核酸构建体，其包括在5’至3’转录方向可操作连接的下列成份(i)能够控制在植物种子细胞内表达之核酸序列；和(ii)编码载脂蛋白多肽之核酸序列；(b)把嵌合核酸构建体导入植物细胞内；
(c)让植物细胞成长为成熟植物；以及(d)从该植物获得种子，其中种子包括载脂蛋白。
种子可用来获得子代植物的群体，各包括表达载脂蛋白的多种种子。在优选的实施方式中，总计种子蛋白至少大约0.25％为载脂蛋白。更优选是总种子蛋白至少大约0.5％为载脂蛋白。优选地是总种子蛋白至少大约1.0％为载脂蛋白。
在优选的实施方式中，得多种转化植物，成长，为所需嵌合核酸序列存在而筛选，其在推定转化体内之存在，可通过例如在使用除草剂抵抗性标志之选择性培养基上的成长来测试，除草剂直接施于植物，或利用Southern DNA印迹法。若检知有嵌合核酸序列存在，即可选用转化植物，以产生子代，终致包括多种种子之成熟植物，种子包括所需嵌合核酸序列。此类种子可用来分离载脂蛋白，或种植以产生随后二代或更多代。一般需种植多种转基因种子，以获得转基因植物群体，各包括有种子，种子包括有编码载脂蛋白之嵌合核酸序列。此外，一般需确保在植物内之纯合性，以保证重组多肽之连续遗传。纯合型植物之选择方法，为本领域人员所知。可用的纯合型植物之获得方法，包含单倍体细胞或组织之制备和转化，接着是单倍体幼苗的再生，随后转变成二倍体植物，例如利用colchine或微管分裂剂加以处理。植物即可按照其它常规农业实践成长。
在另一方面中，本发明亦提供能够结籽表达载脂蛋白之植物。在本发明优选的实施方式中，能够结籽的植物包括嵌合核酸序列，其在5’至3’转录方向包括(a)能够控制植物种子细胞内表达之第一核酸序列，其可操作地连接于；(b)编码载脂蛋白多肽之第二核酸序列，其中种子含有载脂蛋白。
在优选的实施方式中，嵌合核酸序列稳定整合于植物核基因组内。
在又一方面中，本发明提供表达载脂蛋白的植物种子。在本发明优选的实施方式中，植物种子包括嵌合核酸序列，其在5’至3’转录方向包括(a)能够控制植物种子细胞内表达之第一核酸序列，其可操作地连接于；(b)编码载脂蛋白多肽之第二核酸序列。
载脂蛋白多肽可以各种不同形式的种子细胞呈现，包含例如胚轴，包含在胚根和胚叶内，而就单子叶植物品种而言，包含谷物和玉米，用在胚乳组织内。
一旦已获得植物，即可从植物提取而获得载脂蛋白，多少为纯型。
因此，本发明提供基本上纯的载脂蛋白之制备方法，包括(a)提供嵌合核酸构建体，其包括在5’至3’转录方向可操作连接的下列成份(i)能够控制在植物种子细胞内表达之核酸序列；(ii)编码载脂蛋白多肽之核酸序列；(b)把嵌合核酸构建体导入植物细胞内；(c)让植物细胞成长为成熟植物；(d)从该植物获得种子，其中种子包括载脂蛋白；和(e)从植物种子成份分离载脂蛋白，得基本上纯的载脂蛋白。
为从种子成份分离载脂蛋白，植物种子可用任何粉碎法研磨，把种子细胞膜和细胞壁基本上裂解。干、湿研磨条件均可用(美国专利3,971,856号；Lawhon等人，1977，J.Am.Oil Chem.Soc.，63533-534)。在此方面之适当研磨设备，包含胶磨机、盘磨机、IKA磨机、工业规模匀浆器等。选用研磨设备视种子类型和产量要求而定。固体种子污物，例如籽壳、纤维质材料、不溶醣、蛋白质和其它非水溶性污物，均可使用例如基于尺寸排除法，例如过滤，或基于重力法，例如离心，从种子级份除去。在优选的实施方式中，避免使用油提取中常用之有机溶剂，例如己烷，因为此等溶剂会损坏载脂蛋白多肽。正如本发明优选的实施方式中所述，载脂蛋白制造方式是，容许载脂蛋白多肽与种子油体结合，因此，使用例如美国专利6,146,645号所述方法，在种子粉碎后，制备包括载脂蛋白的种子油体。因此本发明亦包含基本上纯的油体，包括由植物种子获得之载脂蛋白。油体可以纯化植物种子级份使用，进一步纯化载脂蛋白。基本上纯的载脂蛋白即可使用各种其他纯化方法，从种子回收，例如基于离心之技术；基于尺寸排除法，包含例如隔膜超滤和交越流动超滤；以及色层分析技术，包含例如离子交换层析、尺寸排除层析、亲和性层析、高效能液体层析(HPLC)、快速蛋白液体层析(FPLC)、疏水性互动层析等。一般而言，使用此等技术的组合，可得基本上纯的载脂蛋白。从转基因植物种子得到天然的基本上纯的载脂蛋白之优选的方法，详见本案实施例6。
药用载脂蛋白配制品可由纯化载脂蛋白制备，如此配制品可用来治疗血管疾病。一般而言，纯化载脂蛋白可与药用载体或稀释剂混合，其量足以施加治疗上有用效果，而对受治疗患者无不良副作用。为配制载脂蛋白组合物，将载脂蛋白重量份溶解、悬浮、分散或其它方式混合于选用载体或稀释剂内，其有效浓度可以改善治疗状况。药用载脂蛋白配制品宜配制成供单剂量投服。人体载脂蛋白的肠外输送用治疗有效剂量，为本领域所公知。若使用载脂蛋白类似物或使用其它输送模式，凡本领域人员可用已知测试方案，或以体内或体外测试资料之外插法，即可轻易实验决定治疗有效剂量。然而，须知浓度和剂量可视要减轻的状况严重性而定。又须知对任何特定对象，可经时按照投服或监督投服配制品的人员之个别判断，加以调节特殊剂量策划。
制药溶液或悬浮液可包含例如无菌稀释剂，例如水、乳糖、蔗糖、磷酸二钙，或羧甲基纤维素。可用载体包含水、盐水溶液、右旋糖水溶液、甘油、二醇类、乙醇等，因而形成溶液或悬浮液。制药组合物可视需要又含有无毒性辅助物质，例如润湿剂；乳化剂；溶解剂；抗菌剂，像苄醇和甲基parabens；抗氧化剂，例如抗坏血酸和亚硫酸氢钠；螯合剂，例如乙二胺四乙酸(EDTA)；pH缓冲剂，例如乙酸盐、柠檬酸盐或磷酸盐缓冲剂；及其组合。
载脂蛋白制剂之最后配制品，一般视载脂蛋白输送模式而定。按照本发明制成的载脂蛋白可以任何所需方式输送；总之，肠外、口服和经鼻的输送形式，均可视为最易行的输送模式。肠外制剂可容纳于安瓶、用完即弃的注射器、单剂量或多剂量的小瓶、由玻璃、塑料或其它适当材料制成均可。
实施例以下实施例是供说明之用，而非作为限制。
实施例1载脂蛋白A-I克隆之构建Apo10Apo10(SEQ ID NO144)系设计来以种子特异方式表达之克隆，其构建如图3(A)、3(B)和3(C)所示。参见2图2，Apo10克隆包含驱使融合蛋白(SEQ ID NO145)在成熟Apo AI和GFP间表达之种子特异启动子和终止子(菜豆蛋白)。为构建此克隆，正向引物1186(SEQ IDNO146)(5’-GGATCCCCtTGGCTAGTAAAGG-3’)，从GFP(由载体pVS-GFP衍生的模板)开始，除去NcoI位点。在终止密码子之后，反向引物1187(SEQ ID NO147)(5’-AAGCTTTCTAGACTGCAGTCATGACTTATTTGTATAGTTC-3’)添加PstI，XbaI和HindIII位点。PCR片段结合入EcoRI克隆载体Topo(Invitrogen)产生质粒G1(图3(A))。正向引物1190(SEQ ID NO148)(5’-CCATGGgg CGGCATTTCTGGCAGCAAGATG-3’)把Apo AI的成熟序列扩增，在基因起始处加NcoI位点。反向引物1189(SEQ IDNO149)(5’-GGATCCcCTGGGTGTTGAGCTTCTTAGTG-3’)除去基因的终止密码子，加BamHI位点，协助产生与GFP(质粒G1)框内翻译融合。这些引物针对的模板是pKS+为基础之载体(Strategene)，含有人体Apo AI基因的整个编码序列。PCR片段结合于Topo克隆载体(Invitrogen)的EcoRI位点，产生质粒M2。含有Apo AI成熟序列的质粒M2，以限制性酶NcoI和BamHI切断。质粒G’1含GFP编码序列，以BamHI和XbaI切断(见图3(B))。M2和G’1的片段一同结合于质粒SBS2090的NcoI和XbaI位点(见图3(B))，产生质粒2M4，质粒2M4以NcoI和HindIII切断，除去Apo AI-GFP融合表达盒，随即使用片段克隆于双载体pSBS4006的NcoI/HindIII位点(见图3(C))。须知此质粒含有来自菜豆的β-菜豆蛋白启动子/终止子(Slightom等人，1983，Proc.Natl.Acad.Sc.USA 801897-1901)，以及pat基因，赋予宿主植物草铵膦抵抗性(Wohlleben等人，1988，Gene 7025-37)，以来自欧芹(Petroselinum crispum)的遍在蛋白启动子/终止子驱动(Kawalleck等人，1993，Plant.Mol.Bio.，21673-684)，供转化为土壤杆菌。
Apo11Apo11(SEQ ID NO150)系设计来以种子特异方式表达之克隆，其构建如图3(A)、3(B)和3(C)所示。参见2图2，Apo11克隆包含驱使融合蛋白(SEQ ID NO151)在Apo AI原和GFP间表达之种子特异启动子和终止子(菜豆蛋白)。为构建此克隆，正向引物1186(SEQ IDNO146)(5’-GGATCCCCtTGGCTAGTAAAGG-3’)，从GFP(由载体pVS-GFP衍生的模板)开始，除去NcoI位点。在终止密码子之后，反向引物1187(SEQ ID NO147)(5’-AAGCTTTCTAGACTGCAGTCATGACTTATTTGTATAGTTC-3’)添加PstI，XbaI和HindIII位点。PCR片段结合入EcoRI克隆载体Topo(Invitrogen)产生质粒G1(图3(A))。正向引物1190(SEQ ID NO148)(5’-CCATGGggCGGCA TTTCTGGCAGCAAGATG-3’)把Apo AI原的序列扩增，在基因起始处加NcoI位点。反向引物1189(SEQ IDNO149)(5’-GGATCCcCTGGGTGTTGAGCTTCTTAGTG-3’)除去基因的终止密码子，加BamHI位点，协助产生与GFP(质粒G1)翻译融合。这些引物针对的模板是pKS+为基础之载体(Strategene)，含有人体Apo AI基因的整个编码序列。PCR片段结合于Topo克隆载体(Invitrogen)的EcoRI位点，产生质粒P2。含有Apo AI原序列的质粒P2，以限制性酶NcoI和BamHI切断。质粒G’1含GFP编码序列，以BamHI和XbaI切断(见图3(B))。P2和G’1的片段一同结合于质粒SBS2090的NcoI和XbaI位点(见图3(B))，产生质粒2P5，质粒2P5以NcoI和HindIII切断，除去Apo AI原-GFP融合表达盒，随即使用片段克隆于双载体pSBS4006的NcoI/HindIII位点(见图3(C))。须知此质粒含有来自菜豆的β-菜豆蛋白启动子/终止子(Slightom等人，1983，Proc.Natl.Acad.Sc.USA 801897-1901)，以及pat基因，赋予宿主植物有草铵膦抵抗性(Wohlleben等人，1988，Gene 7025-37)，以来自欧芹的遍在蛋白启动子/终止子驱动(Kawalleck等人，1993，Plant.Mol.Bio.，21673-684)，供转化为土壤杆菌。
Apo12Apo12(SEQ ID NO153)系设计来以种子特异方式表达之克隆，其构建如图3(A)、3(B)和3(C)所示。参见2图2，Apo12克隆包含驱使融合蛋白(SEQ ID NO154)在油质蛋白(G.J.van Rooijen等人，PlantMol.Biol.18(6)，1177-1179(1992))成熟Apo AI和GFP间表达之种子特异启动子和终止子(菜豆蛋白)。为构建此克隆，正向引物1186(SEQID NO146)(5’-GGATCCCCtTGGCTAGTAAAGG-3’)，从GFP(由载体pVS-GFP衍生的模板)开始，除去NcoI位点。在终止密码子之后，反向引物1187(SEQ ID NO147)(5’-AAGCTTTCTAGACTGCAGTCATGACTTATTTGTATAGTTC-3’)添加PstI，XbaI和HindIII位点。PCR片段结合入EcoRI克隆载体Topo(Invitrogen)产生质粒G1(图3(A))。正向引物1190(SEQ ID NO148)(5’-CCATGGggCGGCA TTTCTGGCAGCAAGATG-3’)把Apo AI的序列扩增，在基因起始处加NcoI位点。反向引物1189(SEQ IDNO149)(5’-GGATCCcCTGGGTGTTGAGCTTCTTAGTG-3’)除去基因的终止密码子，加BamHI位点，协助产生与GFP(质粒G1)框内翻译融合。这些引物针对的模板是pKS+为基础之载体(Strategene)，含有人体Apo AI基因的整个编码序列。PCR片段结合于Topo克隆载体(Invitrogen)的EcoRI位点，产生质粒M2。含有Apo AI成熟序列的质粒M2，以限制性酶NcoI和BamHI切断。质粒G’1含GFP编码序列，以BamHI和XbaI切断(见图3(B))。M2和G’1的片段一同结合于质粒SBS2090的NcoI和XbaI位点(见图3(B))，产生质粒2M4，质粒2M4以NcoI和HindIII切断，除去Apo AI-GFP融合表达盒，随即使用片段克隆于双载体pSBS4006的NcoI/HindIII位点(见图3(C))。须知此质粒含有来自菜豆的β-菜豆蛋白启动子/终止子(Slightom等人，1983，Proc.Natl.Acad.Sc.USA 801897-1901)，控制拟南芥油质蛋白基因的表达(G.J.van Rooijen等人，1992，Plant Mol.Biol.18(6)，1177-1179)，以供与Apo AI/GFP融合进行融合。质粒亦含有pat基因，赋予宿主植物有草铵膦抵抗性(Wohlleben等人，1988，Gene 7025-37)，以来自欧芹的遍在蛋白启动子/终止子驱动(Kawalleck等人，1993，Plant.Mol.Bio.，21673-684)，供转化为土壤杆菌。
Apo13Apo13(SEQ ID NO155)系设计来以种子特异方式表达之克隆，其构建如图3(A)、3(B)和3(C)所示。参见2图2，Apo13克隆包含驱使融合蛋白(SEQ ID NO156)在油质蛋白Apo AI原和GFP间表达之种子特异启动子和终止子(菜豆蛋白)。为构建此克隆，正向引物1186(SEQ ID NO146)(5’-GGATCCCCtTGGCTAGTAAAGG-3’)，从GFP(由载体pVS-GFP衍生的模板)开始，除去NcoI位点。在终止密码子之后，反向引物1187(SEQ ID NO147)(5’-AAGCTTTCTAGACTGCAGTCATGACTTATTTGTATAGTTC-3’)添加PstI，XbaI和HindIII位点。PCR片段结合入EcoRI克隆载体Topo(Invitrogen)产生质粒G1(图3(A))。正向引物1191(SEQ ID NO152)(5’-CCATGGATGAA CCCCCCCAGAGCCCCTG-3’)把Apo AI原的序列扩增，在基因起始处加NcoI位点。反向引物1189(SEQ IDNO149)(5’-GGATCCcCTGGGTGTTGAGCTTCTTAGTG-3’)除去基因终止密码子，加BamHI位点，协助产生与GFP(质粒G1)翻译融合。这些引物针对的模板是pKS+为基础之载体(Strategene)，含有人体Apo AI基因的整个编码序列。PCR片段各分别结合于Topo克隆载体(Invitrogen)的EcoRI位点，产生质粒P2。含有Apo AI原序列的质粒P2，以限制性酶NcoI和BamHI切断。质粒G’1含GFP编码序列，以BamHI和XbaI切断(见图3(B))。P2和G’1的片段一同结合于质粒SBS2090的NcoI和XbaI位点(见图3(B))，产生质粒2P5，质粒2P5以NcoI和HindIII切断，除去Apo AI原-GFP融合表达盒，随即使用片段克隆于双载体pSBS4006的NcoI/HindIII位点(见图3(C))。须知此质粒含有来自菜豆的β-菜豆蛋白启动子/终止子(Slightom等人，1983，Proc.Natl.Acad.Sc.USA 801897-1901)，控制拟南芥油质蛋白基因的表达(G.J.van Rooijen等人，1992，Plant Mol.Biol.18(6)，1177-1179)，供与Apo AI/GFP融合进行融合。质粒亦含有pat基因，赋予宿主植物有草铵膦抵抗性(Wohlleben等人，1988，Gene 7025-37)，以来自欧芹的遍在蛋白启动子/终止子驱动(Kawalleck等人，1993，Plant.Mol.Bio.，21673-684)，供转化为土壤杆菌。
Apo15Apo15(SEQ ID NO157)系设计来以种子特异方式表达之克隆，其构建如图3(A)、3(B)和3(D)所示。参见2图2，Apo15克隆包含驱使融合蛋白(SEQ ID NO158)在成熟Apo AI和GFP间表达之种子特异启动子和终止子(菜豆蛋白)。导向融合蛋白，使用烟草致病相关序列(PRS)信号肽，经由分泌通路表达(Sijmons等人，1990，Bio/technology，8217-221)。为构建此克隆，正向引物1186(SEQ IDNO146)(5’-GGATCCCCtTGGCTAGTAAAGG-3’)，从GFP(由载体pVS-GFP衍生的模板)开始，除去NcoI位点。在终止密码子之后，反向引物1187(SEQ ID NO147)(5’-AAGCTTTCTAGACTGCAGTCATGACTTATTTGTATAGTTC-3’)添加PstI，XbaI和HindIII位点。PCR片段结合入EcoRI克隆载体Topo(Invitrogen)产生质粒G1(图3(A))。正向引物1190(SEQ ID NO148)(5’-CCATGGggCGGCATTT CTGGCAGCAAGATG-3’)把Apo AI的成熟序列扩增，在基因起始处加NcoI位点。反向引物1189(SEQ IDNO149)(5’-GGATCCcCTGGGTGTTGAGCTTCTTAGTG-3’)除去基因之终止密码子，加BamHI位点，协助产生与GFP(质粒G1)框内翻译融合。这些引物针对的模板是pKS+为基础之载体(Strategene)，含有人体Apo AI基因的整个编码序列。PCR片段结合于Topo克隆载体(Invitrogen)的EcoRI位点，产生质粒M2。含有Apo AI成熟序列的质粒M2，以限制性酶NcoI和BamHI切断。质粒G’1含GFP编码序列，以BamHI和XbaI切断(见图3(B))。M2和G’1的片段一同结合于质粒SBS2090的NcoI和XbaI位点(见图3(B))，产生质粒2M4，质粒2M4以NcoI和HindIII切断，除去Apo AI-GFP融合表达盒，随即使用片段克隆于双载体pSBS4011的NcoI/HindIII位点(见图3(D))。须知此质粒含有来自菜豆的β-菜豆蛋白启动子/终止子(Slightom等人，1983，Proc.Natl.Acad.Sc.USA 801897-1901)，融合于PRS信号肽。质粒又含有pat基因，赋予宿主植物有草铵膦抵抗性(Wohlleben等人，1988，Gene7025-37)，以来自欧芹的遍在蛋白启动子/终止子驱动(Kawalleck等人，1993，Plant.Mol.Bio.，21673-684)，供转化为土壤杆菌。
Apo16
Apo16(SEQ ID NO159)系设计来以种子特异方式表达之克隆，其构建如图3(A)、3(B)和3(D)所示。参见2图2，Apo16克隆包含驱使融合蛋白(SEQ ID NO160)在Apo AI原和GFP间表达之种子特异启动子和终止子(菜豆蛋白)。将融合蛋白导向，使用烟草致病相关序列(PRS)信号肽，通过分泌通路表达(Sijmons等人，1990，Bio/technology，8217-221)。为构建此克隆，正向引物1186(SEQ IDNO146)(5’-GGATCCCCtTGGCTAGTAAAGG-3’)，从GFP(由载体pVS-GFP衍生的模板)开始，除去NcoI位点。在终止密码子之后，反向引物1187(SEQ ID NO147)(5’-AAGCTTTCTAGACTGCAGTCATGACTTATTTGTATAGTTC-3’)添加PstI，XbaI和HindIII位点。PCR片段结合入EcoRI克隆载体Topo(Invitrogen)产生质粒G1(图3(A))。正向引物1191(SEQ ID NO152)(5’-CCATGGATGAA CCCCCCCAGAGCCCCTG-3’)把Apo AI原的序列扩增，在基因起始处加NcoI位点。反向引物1189(SEQ IDNO149)(5’-GGATCCcCTGGGTGTTGAGCTTCTTAGTG-3’)除去基因的终止密码子，加BamHI位点，协助产生与GFP(质粒G1)翻译融合。这些引物针对的模板是pKS+为基础之载体(Strategene)，含有人体Apo AI基因的整个编码序列。PCR片段各分别结合于Topo克隆载体(Invitrogen)的EcoRI位点，产生质粒P2。含有Apo AI原序列的质粒P2，以限制性酶NcoI和BamHI切断。质粒G’1含GFP编码序列，以BamHI和XbaI切断(见图3(B))。P2和G’1的片段一同结合于质粒SBS2090的NcoI和XbaI位点(见图3(B))，产生质粒2P5，质粒2P5以NcoI和HindIII切断，除去Apo AI原-GFP融合表达盒，随即使用片段克隆于双载体pSBS4011的NcoI/HindIII位点(见图3(D))。须知此质粒含有来自菜豆的β-菜豆蛋白启动子/终止子(Slightom等人，1983，Proc.Natl.Acad.Sc.USA 801897-1901)，融合于PRS信号肽。质粒又含有pat基因，赋予宿主植物有草铵膦抵抗性(Wohlleben等人，1988，Gene 7025-37)，以来自欧芹的遍在蛋白启动子/终止子驱动(Kawalleck等人，1993，Plant.Mol.Bio.，21673-684)，供转化为土壤杆菌。
Apo17Apo17(SEQ ID NO161)系设计来以组成方式表达之克隆，其构建如图4(A)所示。如2图2，Apo17克隆包含驱使融合蛋白(SEQ IDNO162)在Apo AI和GFP间表达之组成型启动子和终止子(遍在蛋白)。为构建此克隆，质粒2M4(见图3(B))以NcoI和PstI切断，除去Apo AI-GFP融合表达盒，将片段结合于质粒pKUO3’的NcoI和PstI位点，产生质粒KU2M4。pKUO3’质粒含油菜油质蛋白基因，在NcoI和PstI切断载体时除去，于香芹遍在蛋白启动子和遍在蛋白终止子控制下，得Apo AI/GFP融合构建体(P.Kawalleck等人，1993，Plant.Mol.Bio.，21673-684)。KU2M4质粒以KpnI切断，结合于双载体SBS3000的KpnI位点(见图4)。须知此质粒含有pat基因，赋予宿主植物有草铵膦抵抗性(Wohlleben等人，1988，Gene 7025-37)，以来自欧芹的遍在蛋白启动子/终止子驱动(Kawalleck等人，1993，Plant.Mol.Bio.，21673-684)，供转化为土壤杆菌。Apo17克隆含有成熟Apo AI-GFP翻译融合体，并且导向细胞质。
Apo18aApo18a(SEQ ID NO163)系设计来以组成方式表达之克隆，其构建如图4所示。如2图2，Apo18a克隆包含驱使融合蛋白(SEQ IDNO164)在Apo AI原和GFP间表达之组成型启动子和终止子(遍在蛋白)。为构建此克隆，质粒2P5(见图3(B))以NcoI和PstI切断，除去Apo AI原-GFP融合表达盒，将片段结合于质粒pKUO3’的NcoI和PstI位点，产生质粒KU2P5。pKUO3’质粒含油菜油质蛋白基因，在NcoI和PstI切断载体时除去，于香芹遍在蛋白启动子和遍在蛋白终止子控制下，得Apo AI原/GFP融合构建体(P.Kawalleck等人，1993，Plant.Mol.Bio.，21673-684)。KU2P5质粒以KpnI切断，结合于双载体SBS3000的KpnI位点(见图4)。须知此质粒含有pat基因，赋予宿主植物有草铵膦抵抗性(Wohlleben等人，1988，Gene 7025-37)，以来自欧芹的遍在蛋白启动子/终止子驱动(Kawalleck等人，1993，Plant.Mol.Bio.，21673-684)，供转化为土壤杆菌。Apo18a克隆含有成熟Apo AI原-GFP翻译融合体，并且导向细胞质。
Apo18bApo18b(SEQ ID NO163)系设计来以组成方式表达之克隆，其构建如图4(B)所示。如2图2，Apo18b克隆包含驱动融合蛋白(SEQID NO164)在Apo AI原和GFP间表达之组成型启动子和终止子(遍在蛋白)。须知Apo18a和Apo 18b二克隆均有驱动融合蛋白(SEQ IDNO164)在Apo AI和GFP间表达之组成型启动子(遍在蛋白)。二克隆间之差异在于，Apo18a插入双载体pSBS3000之KpnI位点，含有pat基因，赋予宿主植物有草铵膦抵抗性(Wohlleben等人，1988，Gene7025-37)，由来自欧芹的遍在蛋白启动子/终止子驱动(Kawalleck等人，1993，Plant.Mol.Bio.，21673-684)，供转化为土壤杆菌。相对地，Apo18b插入双载体pSBS5001(含有pmi基因)之KpnI位点(Miles等人，1984，Gene 2141-48)，为磷酸甘露糖异构酶编码，容许正面选择含甘露糖之选择培养基。pmi基因在来自欧芹的遍在蛋白启动子/终止子控制下(Kawalleck等人，1993，Plant.Mol.Bio.，21673-684)，供转化为土壤杆菌。为构建此克隆，Apo18a双载体以KpnI切断，除去Apo AI原-GFP融合表达盒，将片段结合于质粒SBS5001之KpnI位点，供在土壤杆菌内表达。Apo18b克隆含Apo AI原-GFP翻译融合体，并导向细胞质。
Apo19Apo19(SEQ ID NO165)系设计来以组成方式表达之克隆，其构建如图5(A)和5(B)所示。参见2图2，Apo19克隆包含驱动融合蛋白(SEQ ID NO166)在Apo AI和GFP间表达之组成型启动子和终止子(遍在蛋白)。融合蛋白使用烟草致病相关序列(PRS)信号肽进行导向，通过分泌途径而表达(Sijmons等人，1990，Bio/technology，8217-221)。为构建此克隆，使用Apo15为模板。正向引物1177(SEQ IDNO167)(5’-GCAGCATTCATGAACTTCCTTAA GTCTTT CC-3’)，把在起始密码子含有BspHI位点的植物前序列(PRS)开始扩增。反向引物1178(SEQ ID NO168)(5’-GGTGGTGGATCCcCTGGGTGTTGAGCTTCTTAGTG-3’)除去基因的终止密码子，加BamHI位点，以助产生与GFP之框内翻译融合体。二引物末端留下额外碱基，以方便限制性酶消化。G1质粒(见图3(A))以BamHI和PstI消化，供结合于pubiP+iS3’，后者含有来自欧芹的遍在蛋白启动子和终止子(Kawalleck等人，1993，Plant.Mol.Bio.，21673-684)。PRS-Apo AI PCR片段以BspHI和BamHI消化，并以G1片段结合于质粒pubiP+iS3’内，产生质粒19-6。质粒19-6以EcoRI消化，除去表达表达盒，表达盒再结合于质粒pKUO3’内(图4(A))，于EcoRI位点间(除去现有表达盒)，产生质粒KU19-6。KU19-6以KpnI消化，将片段结合于质粒SBS3000之KpnI位点(图5(B))。须知此质粒含pat基因，赋予宿主植物有草铵膦抵抗性(Wohlleben等人，1988，Gene 7025-37)，以来自欧芹的遍在蛋白启动子/终止子驱动(Kawalleck等人，1993，Plant.Mol.Bio.，21673-684)，供转化为土壤杆菌。Apo19克隆含有成熟Apo AI-GFP翻译融合体，分别导向分泌通路。
Apo20Apo20(SEQ ID NO169)系设计来以组成方式表达之克隆，其构建如图5(A)和5(B)所示。参见2图2，Apo20克隆包含驱动融合蛋白(SEQ ID NO170)在Apo AI原和GFP间表达之组成型启动子和终止子(遍在蛋白)。融合蛋白使用烟草致病相关序列(PRS)信号肽进行导向，通过分泌系统而表达(Sijmons等人，1990，Bio/technology，8217-221)。为构建此克隆，使用Apo16为模板。正向引物1177(SEQ IDNO167)(5’-GCAGCATTCATGAACTTCCTTAA GTCTTT CC-3’)，把在起始密码子含有BspHI位点的植物前序列(PRS)开始扩增。反向引物1178(SEQ ID NO168)(5’-GGTGGTGGATCCcCTGGGTGTTGAGCTTCTTAGTG-3’)除去基因的终止密码子，加BamHI位点，以助产生与GFP之框内翻译融合体。二引物末端留下额外碱基，以方便限制性酶消化。G1质粒(见图3(A))以BamHI和PstI消化，供结合于pubiP+iS3’，后者含有来自欧芹的遍在蛋白启动子和终止子(Kawalleck等人，1993，Plant.Mol.Bio.，21673-684)。PRS-Apo AI原PCR片段以BspHI和BamHI消化，并以G1片段结合于质粒pubiP+iS3’内，产生质粒20-11。质粒20-11以EcoRI消化，除去表达表达盒，表达盒再结合于质粒pKUO3’内(图4(A))，于EcoRI位点间(除去现有表达盒)，产生质粒KU20-11。KU20-11以KpnI消化，将片段结合于质粒SBS3000之KpnI位点(图5(B))。须知此质粒含pat基因，赋予宿主植物有草铵膦抵抗性(Wohlleben等人，1988，Gene 7025-37)，以来自欧芹的遍在蛋白启动子/终止子驱动(Kawalleck等人，1993，Plant.Mol.Bio.，21673-684)，供转化为土壤杆菌。Apo20克隆相应地含有成熟Apo AI原-GFP翻译融合体，导向分泌通路。
Apo21Apo21(SEQ ID NO171)是种子优选的克隆，其构建如图6所示。参见2图2，Apo21克隆包含驱动Apo AI(SEQ ID NO172)表达之种子优选启动子和终止子(菜豆蛋白)。为构建此克隆，正向引物1203(SEQ ID NO173)(5’-GCAGCACCATGGATGAACCCCCCCAGAGCCCCTG-3’)，于成熟ApoAI开始，加NcoI位点。反向引物1206(SEQ ID NO174)(5’-GTGGTGAAGCTTTCACTGGGTGTTGAGCTTCTTAGTGTACTCCTCcAGAGCG-3’)，在终止密码子后加HindIII位点，加沉默突变，以除去第二XhoI位点。二引物在5’末端含额外碱基，以方便限制性酶消化。PCR片段以NcoI和HindIII消化，并结合于质粒SBS2090，产生质粒5-3(图6)。质粒5-3以NcoI和HindIII消化，而将Apo AI片段结合于SBS4006的NcoI/HindIII位点(图3(C))。SBS4006含有来自菜豆的β—菜豆蛋白启动子/终止子(Slightom等人，1983，Proc.Natl.Acad.Sc.USA 801897-1901)，和pat基因，赋予宿主植物有草铵膦抵抗性(Wohlleben等人，1988，Gene 7025-37)，利用来自欧芹的遍在蛋白启动子/终止子驱动(Kawalleck等人，1993，Plant.Mol.Bio.，21673-684)，供转化为土壤杆菌。Apo21是具有种子特异性克隆，把Apo AI导向细胞质。
Apo22Apo22(SEQ ID NO175)是种子优选的克隆，其构建如图7所示。参见2图2，Apo22克隆包含驱动Apo AI原(SEQ ID NO176)表达之种子优选启动子和终止子(菜豆蛋白)。为构建此克隆，正向引物1201(SEQ ID NO177)(5’-GCAGCACCATGGggCGGCATTTCTGGCAGCAAGATG-3’)，于成熟Apo AI原开始，加NcoI位点。反向引物1206(SEQ ID NO174)(5’-GTGGTGAAGCTTTCACTGGGTGTTGAGCTTCTTAGTGTACTCCTCcAGAGCG-3’)，在终止密码子后加HindIII位点，加沉默突变，以除去第二XhoI位点。二引物在5’末端含额外碱基，以方便限制性酶消化。PCR片段以NcoI和HindIII消化，并结合于质粒SBS2090(图3(B))，产生质粒4-2(图7)。质粒4-2以NcoI和HindIII消化，而将Apo AI原片段结合于SBS4006的NcoI/HindIII位点(图3(C))。SBS4006含有来自菜豆的β-菜豆蛋白启动子/终止子(Slightom等人，1983，Proc.Natl.Acad.Sc.USA 801897-190I)，和pat基因，赋予宿主植物有草铵膦抵抗性(Wohlleben等人，1988，Gene 7025-37)，利用来自欧芹的遍在蛋白启动子/终止子驱动(Kawalleck等人，1993，Plant.Mol.Bio.，21673-684)，供转化为土壤杆菌。Apo22具有种子特异性克隆，把Apo AI导向细胞质。
Apo23Apo23(SEQ ID NO178)是种子优选的克隆，其构建如图6所示。参见2图2，Apo23克隆包含驱动油质蛋白Apo AI(SEQ ID NO179)表达之种子优选启动子和终止子(菜豆蛋白)。为构建此克隆，正向引物1203(SEQ ID NO173)(5’-GCAGCACCATGGATGAACCCCCCCAGAGCCCC TG-3’)，于成熟ApoAI开始，加NcoI位点。反向引物1206(SEQ ID NO174)(5’-GTGGTGAAGCTTTCACTGGGTGTTGAGCTTCTTAGTGTACTCCTCcAGAGCG-3’)，在终止密码子后加HindIII位点，加沉默突变，以除去第二XhoI位点。二引物在5’末端含额外碱基，以方便限制性酶消化。PCR片段以NcoI和HindIII消化，并结合于质粒SBS2090，产生质粒5-3(图6)。质粒5-3以NcoI和HindIII消化，而将Apo AI片段结合于SBS4006的NcoI/HindIII位点(图3(C))。SBS4008含有来自菜豆的β-菜豆蛋白启动子/终止子(Slightom等人，1983，Proc.Natl.Acad.Sc.USA 801897-1901)，以控制拟南芥油质蛋白基因之表达(G.J.vanRooijen等人，1992，Plant Mol.Biol.18(6)，1177-1179)，并含有pat基因，赋予宿主植物有草铵膦抵抗性(Wohlleben等人，1988，Gene 7025-37)，利用来自欧芹的遍在蛋白启动子/终止子驱动(Kawalleck等人，1993，Plant.Mol.Bio.，21673-684)，供转化为土壤杆菌。Apo23具有种子特异性克隆，把油质蛋白Apo AI导向油体。
Apo24Apo24(SEQ ID NO180)是种子优选的克隆，其构建如图7所示。参见2图2，Apo24克隆包含驱动油质蛋白Apo AI(SEQ ID NO181)表达之种子优选启动子和终止子(菜豆蛋白)。为构建此克隆，正向引物1201(SEQ ID NO177)(5’-GCAGCACCATGGggCGGCATTTCTGGCAGCAA GATG-3’)，于成熟Apo AI原开始，加NcoI位点。反向引物1206(SEQ ID NO174)(5’-GTGGTGAAGCTTTCACTGGGTGTTGAGCTTCTTAGTGTACTCCTCcAGAGCG-3’)，在终止密码子后加HindIII位点，加沉默突变，以除去第二XhoI位点。二引物在5’末端含额外碱基，以方便限制性酶消化。PCR片段以NcoI和HindIII消化，并结合于质粒SBS2090，产生质粒4-2(图7)。质粒4-2以NcoI和HindIII消化，而将Apo AI原片段结合于SBS4008的NcoI/HindIII位点(图3(C))。SBS4008含有来自菜豆的β—菜豆蛋白启动子/终止子(Slightom等人，1983，Proc.Natl.Acad.Sc.USA 801897-1901)，控制拟南芥油质蛋白基因之表达(G.J.vanRooijen等人，1992，Plant Mol.Biol.18(6)，1177-1179)，并含有pat基因，赋予宿主植物有草铵膦抵抗性(Wohlleben等人，1988，Gene 7025-37)，利用来自欧芹的遍在蛋白启动子/终止子驱动(Kawalleck等人，1993，Plant.Mol.Bio.，21673-684)，供转化为土壤杆菌。Apo24具有种子特异性克隆，把油质蛋白Apo AI原导向油体。
Apo25Apo25(SEQ ID NO182)是种子优选的克隆，其构建如图6所示。参见2图2，Apo25克隆包含驱动油质蛋白/klip8/met/Apo AI(SEQID NO183)表达之种子优选启动子和终止子(菜豆蛋白)。此构建体具有klip8裂解序列(SEQ ID NO143)，以方便融合蛋白用凝乳酶裂解，为构建此克隆，正向引物1203(SEQ ID NO173)(5’-GCAGCACCAT GGATGAACCCCCCCAGAGCCCCTG-3’)，于成熟ApoAI开始，加NcoI位点。反向引物1206(SEQ ID NO174)(5’-GTGGTGAAGCTTTCACTGGGTGTTGAGCTTCTTAGTGTACTCCTCcAGAGCG-3’)，在终止密码子后加HindIII位点，加沉默突变，以除去第二XhoI位点。二引物在5’末端含额外碱基，以方便限制性酶消化。PCR片段以NcoI和HindIII消化，并结合于质粒SBS2090(图3(B))，产生质粒5-3(图6)。质粒5-3以NcoI和HindIII消化，而将Apo AI片段结合于SBS4010的NcoI/HindIII位点(图7)。SBS4010含有来自菜豆的β-菜豆蛋白启动子/终止子(Slightom等人，1983，Proc.Natl.Acad.Sc.USA 801897-1901)，控制拟南芥油质蛋白基因的表达(G.J.vanRooijen等人，1992，Plant Mol.Biol.18(6)，1177-1179)和klip8裂解位点，质粒亦含有pat基因，赋予宿主植物有草铵膦抵抗性(Wohlleben等人，1988，Gene 7025-37)，利用来自欧芹的遍在蛋白启动子/终止子驱动(Kawalleck等人，1993，Plant.Mol.Bio.，21673-684)，供转化为土壤杆菌。Apo25具有种子特异性克隆，把油质蛋白/klip8/met/Apo AI导向油体，且使用klip8裂解序列纯化。
Apo26Apo26(SEQ ID NO184)是种子优选的克隆，其构建如图7所示。参见2图2，Apo26克隆包含驱动油质蛋白/klip8/met/Apo AI原(SEQ ID NO185)表达之种子优选启动子和终止子(菜豆蛋白)。此构建体具有klip8裂解序列(SEQ ID NO143)，以方便融合蛋白用凝乳酶裂解，为构建此克隆，正向引物1201(SEQ ID NO177)(5’-GCAGC ACCATGGggCGGCATTTCTGGCAGCAAGATG-3’)，于Apo AI原开始，加NcoI位点。反向引物1206(SEQ ID NO174)(5’-GTGGTGAAGCTTTCACTGGGTGTTGAGCTTCTTAGTGTACTCCTCcAGAGCG-3’)，在终止密码子后加HindIII位点，加沉默突变，以除去第二XhoI位点。二引物在5’末端含额外碱基，以方便限制性酶消化。PCR片段以NcoI和HindIII消化，并结合于质粒SBS2090(图3(B))，产生质粒4-2(图7)。质粒4-2以NcoI和HindIII消化，而将met-ApoAI原片段结合于SBS4010的BspHI/HindIII位点(图7)。SBS4010含有来自菜豆的β-菜豆蛋白启动子/终止子(Slightom等人，1983，Proc.Natl.Acad.Sc.USA 801897-1901)，控制拟南芥油质蛋白基因之表达(G.J.van Rooijen等人，1992，Plant Mol.Biol.18(6)，1177-1179)，和klip8裂解位点。质粒又含有pat基因，赋予宿主植物有草铵膦抵抗性(Wohlleben等人，1988，Gene 7025-37)，利用来自欧芹的遍在蛋白启动子/终止子驱动(Kawalleck等人，1993，Plant.Mol.Bio.，21673-684)，供转化为土壤杆菌。Apo26具有种子特异性克隆，把油质蛋白/klip8/met/Apo AI原导向油体，并使用klip8裂解序列纯化。
Apo27Apo27(SEQ ID NO186)是种子优选克隆，其构建如图8(A)所示。参见2图2，Apo27使用拟南芥油质蛋白序列，为表达而导向油体(G.J.van Rooijen等人，1992，Plant Mol.Biol.18(6)，1177-1179)，并具有klip8裂解序列(SEQ ID NO143)，以方便融合蛋白用凝乳酶裂解。为构建此克隆，正向引物1200(SEQ ID NO188)(5’-GCAGCACTCGAGcaagttcCGGCATTTCTGGCAGCAAGA-3’)，加XhoI位点和额外核苷酸，以便Apo AI原开始时，在框内克隆于klip8(SEQID NO143)裂解序列。反向引物1206(SEQ ID NO174)(5’-GTGGTGAAGCTTTCACTGGGTGTTGAGCTTCTTAGTGTACTCCTCcAGAGCG-3’)，在终止密码子后加HindIII位点，加沉默突变，以除去第二XhoI位点。这些引物针对的模板为Apo33质粒，含原型Apo AI，无内部XhoI位点和另外Met残基。PCR片段以XhoI切断，并结合于pKS+的XhoI/EcoRV位点，产生质粒6-3。质粒6-3以XhoI和HindIII切断，并结合于双载体SBS4010的XhoI/HindIII位点(图7)。须知SBS4010含有来自菜豆的β-菜豆蛋白启动子/终止子(Slightom等人，1983，Proc.Natl.Acad.Sc.USA 801897-1901)，控制拟南芥油质蛋白基因(G.J.van Rooijen等人，1992，Plant Mol.Biol.18(6)，1177-1179)和klip8裂解位点的表达。质粒亦含有pat基因，赋予宿主植物有草铵膦抵抗性(Wohlleben等人，1988，Gene 7025-37)，利用来自欧芹的遍在蛋白启动子/终止子驱动(Kawalleck等人，1993，Plant.Mol.Bio.，21673-684)，供转化为土壤杆菌。Apo27是种子特异性克隆，把Apo AI导向油体，并以裂解序列klip8纯化。
Apo27MApo27M(SEQ ID NO189)是种子优选的克隆，其构建如图8(B)所示。参见2图2，Apo27M克隆包含驱动油质蛋白/klip8/met/Apo AI-M(SEQ ID NO190)之种子优选启动子和终止子(菜豆蛋白)。此构建体具有klip8裂解序列(SEQ ID NO143)，以方便融合蛋白用凝乳酶裂解。为构建此克隆，正向引物1202(5’-GCAGCACTCGAGcaagttcGATGAACCCCCCCAGAGCCC-3’)(SEQ ID NO191)于mat-Apo AI开始，加XhoI位点和额外核苷酸，以便利框内克隆于klip8裂解序列。正向引物1225(5’-CGCCAGt GCTTGGCCGCGCGCCTTG-3’)(SEQ IDNO192)是平端引物，使碱基对从C突变至T，把Arg残基变成Cys残基。反向引物1206(5’-GTGGTGAAGCTTTCACTGGGTGTTGAGCTTCTTAGTGTACTCCTCcAGAGCG-3’)(SEQ ID NO174)，于终止密码子之后加HindIII，并加沉默突变，以除去第二XhoI位点。二引物都在5’末端含额外碱基，以方便限制性酶消化。这些引物针对的模板是质粒P-10，在其XhoI位点已有突变。双链模板已利用DpnI消化除去。PCR片段用XhoI和HindIII消化，结合于质粒pKS+XhoI/HindIII位点，产生质粒ApoM。ApoM以XhoI和HindIII消化，把片段结合于质粒SBS4010的XhoI/HindIII位点(图7)，SBS4010含有来自菜豆的β-菜豆蛋白启动子/终止子(Slightom等人，1983，Proc.Natl.Acad.Sc.USA 801897-1901)，控制拟南芥油质蛋白基因(G.J.van Rooijen等人，1992，Plant Mol.Biol.18(6)，1177-1179)，以及klip8裂解位点之表达。质粒亦含有pat基因，赋予宿主植物有草铵膦抵抗性(Wohlleben等人，1988，Gene 7025-37)，利用来自欧芹的遍在蛋白启动子/终止子驱动(Kawalleck等人，1993，Plant.Mol.Bio.，21673-684)，供转化为土壤杆菌。Apo27M是种子特异性克隆，把油质蛋白/klip8/met/Apo AI-M导向油体，使用klip8裂解序列纯化。
Apo28Apo28(SEQ ID NO193)是种子优选的克隆，其构建如图9所示。参见2图2，Apo28克隆包含驱动油质蛋白/klip8/met/Apo AI原(SEQ ID NO194)之种子优选启动子和终止子(菜豆蛋白)。为构建此克隆，正向引物1200(5’-GCAGCACTCGAGcaagttcCGGCATTTCTGGCAGCAAGA-3’)(SEQ IDNO188)于Apo AI原开始，加XhoI位点和额外核苷酸，以便利框内克隆于klip8裂解序列。正向引物1205(5’-CCAAGCCCGCGCTaGAGGACCTCCG-3’)(SEQ ID NO195)是平端引物，加沉默突变，以除去第一XhoI位点。反向引物1206(5’-GTGGTGAAGCTTTCACTGGGTGTTGAGCTTCTTAGTGTACTCCTCcAGAGCG-3’)(SEQ ID NO174)，于终止密码子之后加HindIII，并加沉默突变，以除去第二XhoI位点。二引物都在5’末端含额外碱基，以方便限制性酶消化。这些引物针对的模板是pKS+为基础之载体(Stratagene)，含有人体Apo AI基因用之整个编码序列。双链模板已利用DpnI消化除去。PCR片段用XhoI和HindIII消化，结合于质粒pKS+XhoI/HindIII位点，产生质粒P-10。P-10以XhoI和HindIII消化，把片段结合于质粒SBS4010的XhoI/HindIII位点(图7)，须知SBS4010含有来自菜豆的β-菜豆蛋白启动子/终止子(Slightom等人，1983，Proc.Natl.Acad.Sc.USA 801897-1901)，控制拟南芥油质蛋白基因(G.J.van Rooijen等人，1992，Plant Mol.Biol.18(6)，1177-1179)，以及klip8裂解位点之表达。质粒亦含有pat基因，赋予宿主植物有草铵膦抵抗性(Wohlleben等人，1988，Gene 7025-37)，利用来自欧芹的遍在蛋白启动子/终止子驱动(Kawalleck等人，1993，Plant.Mol.Bio.，21673-684)，供转化为土壤杆菌。Apo28是Apo AI原克隆，导向油体，且可在klip8序列裂解。
Apo29Apo29(SEQ ID NO196)是种子优选克隆，其构建如图6所示。参见2图2，Apo29克隆包含驱动PRS-Apo AI(SEQ ID NO197)表达的种子优选启动子和终止子(菜豆蛋白)。Apo29使用烟草致病相关序列(PRS)信号肽，为表达而导向分泌通路(Sijmons等人，1990，Bio/technology，8217-221)。为构建此克隆，正向引物1203(SEQ IDNO173)(5’-GCAGCACCATGGATGAACCCCCCCAGAGCCCCTG-3’)于成熟Apo AI开始，加NcoI位点。反向引物1206(SEQ ID NO174)(5’-GTGGTGAAGCTTTCACTGGGTGTTGAGCTTCTTAGTGTACTCCTCcAGAGCG-3’)于终止密码子后加HindIII位点，加沉默突变，以除去第二XhoI位点。二引物在5’末端含有额外碱基，以方便限制性酶消化。PCR片段以NcoI和HindIII消化，并结合于质粒SBS2090，产生质粒5-3(图6)。质粒5-3以NcoI和HindIII消化，而Apo AI片段结合于SBS4011的NcoI/HindIII位点(图3D图)。SBS4011含来自菜豆的β-菜豆蛋白启动子/终止子(Slightom等人，1983，Proc.Natl.Acad.Sc.USA 801897-1901)，控制拟南芥油质蛋白基因(G.J.van Rooijen等人，1992，Plant Mol.Biol.18(6)，1177-1179)和PRS信号肽(Sijmons等人，1990，Bio/technology，8217-221)的表达。质粒亦含有pat基因，赋予宿主植物有草铵膦抵抗性(Wohlleben等人，1988，Gene 7025-37)，利用来自欧芹的遍在蛋白启动子/终止子驱动(Kawalleck等人，1993，Plant.Mol.Bio.，21673-684)，供转化为土壤杆菌。Apo29是种子特异性克隆，把Apo AI导向分泌通路。
Apo30Apo30(SEQ ID NO198)是种子优选克隆，其构建如图7所示。参见2图2，Apo30克隆包含驱动PRS-Apo AI原(SEQ ID NO199)表达的种子优选启动子和终止子(菜豆蛋白)。Apo AI原使用烟草致病相关序列(PRS)信号肽，为表达而导向分泌通路(Sijmons等人，1990，Bio/technology，8217-221)。为构建此克隆，正向引物1201(SEQ IDNO177)(5’-GCAGC ACCATGGggCGGCATTTCTGGCAGCAAGATG-3’)，于Apo AI原开始，加NcoI位点。反向引物1206(SEQ IDNO174)(5’-GTGGTGAAGCTTTCACTGGGTGTTGAGCTTCTTAGTGTACTCCTCcAGAGCG-3’)于终止密码子后加HindIII位点，加沉默突变，以除去第二XhoI位点。二引物在5’末端含额外碱基，以方便RE消化。PCR片段以NcoI和HindIII消化，并结合于质粒SBS2090，产生质粒4-2(图7)。质粒4-2以NcoI和HindIII消化，而Apo AI片段结合于SBS4011的NcoI/HindIII位点(图3D图)。SBS4011含来自菜豆的β-菜豆蛋白启动子/终止子(Slightom等人，1983，Proc.Natl.Acad.Sc.USA 801897-1901)，控制拟南芥油质蛋白基因(G.J.van Rooijen等人，1992，Plant Mol.Biol.18(6)，1177-1179)和PRS信号肽(Sijmons等人，1990，Bio/technology，8217-221)的表达。质粒亦含有pat基因，赋予宿主植物有草铵膦抵抗性(Wohlleben等人，1988，Gene 7025-37)，利用来自欧芹的遍在蛋白启动子/终止子驱动(Kawalleck等人，1993，Plant.Mol.Bio.，21673-684)，供转化为土壤杆菌。Apo30是种子特异性克隆，把Apo AI原导向分泌通路。
Apo31Apo31(SEQ ID NO200)是种子优选克隆，其构建如图8(A)所示。参见2图2，Apo31克隆表示驱动PRS/D9 scFV/Apo AI(SEQ IDNO201)融合蛋白表达的种子优选启动子和终止子(菜豆蛋白)。D9ScFV/Apo AI使用烟草致病相关序列(PRS)信号肽，为表达而导向分泌通路(Sijmons等人，1990，Bio/technology，8217-221)。为构造此克隆，正向引物1200(SEQ ID NO188)(5’-GCAGCACTCGAGcaagttcCGGCATTTCTGGCAGCAAGA-3’)于Apo AI原开始，加XhoI位点。反向引物1206(SEQ ID NO174)(5’-GTGGTGAAGCTTTCACTGGGTGTTGAGCTTCTTAGTGTACTCCTCcAGAGCG-3’)于终止密码子后，加HindIII位点，并加沉默突变，以除去第二XhoI位点。这些引物针对的模板为Apo33质粒，含有Apo AI原型，无内部XhoI位点和另外Met残基。PCR片段以XhoI切断，结合于pKS+的XhoI/EcoRV位点，产生质粒6-3。质粒6-3以XhoI和HindIII切断，并结合于双载体SBS4055的XhoI/HindIII位点(图9)。须知SBS4055含有来自菜豆的β-菜豆蛋白启动子/终止子(Slightom等人，1983.Proc.Natl.Acad.Sc.USA 801897-1901)，控制框内融合于D9scFV/Apo AI插段的PRS信号序列表达。质粒亦含有pat基因，赋予宿主植物有草铵膦抵抗性(Wohlleben等人，1988，Gene 7025-37)，利用来自欧芹的遍在蛋白启动子/终止子驱动(Kawalleck等人，1993，Plant.Mol.Bio.，21673-684)，供转化为土壤杆菌。Apo31是种子特异性克隆，把Apo AI导向分泌通路，以油质蛋白D9scFV抗体纯化。
Apo32Apo32(SEQ ID NO202)是种子优选克隆，其构建如图9所示。参见2图2，Apo32克隆表示驱动D9 scFV/Apo AI原(SEQ ID NO203)表达的种子优选启动子和终止子(菜豆蛋白)。为构建此克隆，正向引物1200(SEQ ID NO188)(5’-GCAGCACTCGAGcaagttcCGGCATTTCTGGCAGC AAGA-3’)于Apo AI原开始，加XhoI位点。正向引物1205(SEQ ID NO195)(5’-CCAAGCCCGCGCTaGAGGACC TCCG-3’)是平端引物，加沉默突变，以除去第一XhoI位点。反向引物1206(SEQ ID NO174)(5’-GTGGTGAAGCTTTCACTGGGTGTTGAGCTTCTTAGTGTACTCCTCcAGAGCG-3’)于终止密码子后，加HindIII位点，并加沉默突变，以除去第二XhoI位点。二引物均在5’末端含额外碱基，以方便限制性酶消化。这些引物针对的模板为pKS+为基础之载体(Stratagene)，含有人体Apo AI基因用整个编码序列。双链模板利用DpnI消化除去。PCR片段以XhoI和HindIII消化，结合于质粒pKS+XhoI/EcoRV位点，产生质粒P-10。质粒P-10以XhoI和HindIII消化，并将片段结合于质粒SBS4055的XhoI/HindIII位点(图9)。须知SBS4055含有来自菜豆的β-菜豆蛋白启动子/终止子(Slightom等人，1983，Proc.Natl.Acad.Sc.USA 801897-1901)，控制框内融合于D9scFV抗体的PRS信号序列表达。质粒亦含有pat基因，赋予宿主植物有草铵膦抵抗性(Wohlleben等人，1988，Gene 7025-37)，利用来自欧芹的遍在蛋白启动子/终止子驱动(Kawalleck等人，1993，Plant.Mol.Bio.，21673-684)，供转化为土壤杆菌。Apo32克隆把框内融合于油质蛋白抗体D9的Apo AI原导向分泌通路，以助纯化。
Apo33Apo33(SEQ ID NO204)是种子优选克隆，其构建如图10所示。参见2图2，Apo33克隆表示驱动PRS/D9 scFV/met/Apo AI(SEQID NO205)融合蛋白表达的种子优选启动子和终止子(菜豆蛋白)。D9 ScFV/met/Apo AI使用烟草致病相关序列(PRS)信号肽，为表达而导向分泌通路(Sijmons等人，1990，Bio/technology，8217-221)。为构建此克隆，正向引物1203(SEQ ID NO173)(5’-GCAGCACCATGGATGAACCCCCCCAGAGCCCCTG-3’)于成熟ApoAI原开始，加NcoI位点。反向引物1206(SEQ ID NO174)(5’-GTGGTGAAGCTTTCACTGGGTGTTGAGCTTCTTAGTGTACTCCTCcAGAGCG-3’)于终止密码子后，加HindIII位点，并加沉默突变，以除去第二XhoI位点。二引物均在5’末端含额外碱基，以方便限制性酶消化。这些引物针对的模板为P-10质粒，含有Apo AI原型，无内部XhoI位点。PCR片段以NcoI和HindIII消化，结合于pSBS2090的XhoI/EcoRV位点，产生质粒20-2。质粒以NcoI和HindIII切断，并结合于pSBS4010载体BspHI/HindIII位点(图9)。产生质粒4010+20-2。质粒以XhoI和HindIII切断，将片段结合于双载体SBS4055的XhoI/HindIII位点(图10)。须知SBS4055含有来自菜豆的β-菜豆蛋白启动子/终止子(Slightom等人，1983，Proc.Natl.Acad.Sc.USA 801897-1901)，控制框内融合于D9 scFV抗体的PRS信号序列表达。质粒亦含有pat基因，赋予宿主植物有草铵膦抵抗性(Wohlleben等人，1988，Gene 7025-37)，利用来自欧芹的遍在蛋白启动子/终止子驱动(Kawalleck等人，1993，Plant.Mol.Bio.，21673-684)，供转化为土壤杆菌。Apo33是种子特异性克隆，把Apo AI导向分泌通路，并与油质蛋白抗体D9框内融合，以助纯化。
Apo34Apo34(SEQ ID NO206)是种子优选克隆，其构建如图10所示。参见2图2，Apo34克隆表示驱动PRS/D9 scFV/met/Apo AI原(SEQ ID NO207)融合蛋白表达的种子优选启动子和终止子(菜豆蛋白)。D9 ScFV/met/Apo AI原使用烟草致病相关序列(PRS)信号肽，为表达而导向分泌通路(Sijmons等人，1990，Bio/technology，8217-221)。为构建此克隆，正向引物1201(SEQ ID NO177)(5’-GCAGCACCATGGggCGGCATTTCTGGCAGCAAGATG-3’)于Apo AI原开始，加NcoI位点。反向引物1206(SEQ ID NO174)(5’-GTGGTGAAGCTTTCACTGGGTGTTGAGCTTCTTAGTGTACTCCTCcAGAGCG-3’)于终止密码子后，加HindIII位点，并加沉默突变，以除去第二XhoI位点。二引物均在5’末端含额外碱基，以方便限制性酶消化。这些引物针对的模板为P-10质粒，含有Apo AI原型，无内部XhoI位点。PCR片段以NcoI和HindIII消化，结合于pSBS2090的NcoI/HindIII位点(图3(B))，产生质粒19-2。质粒以NcoI和HindIII切断，将片段结合于SBS4010载体BspHI/HindIII位点，产生质粒4010+19-2。质粒以XhoI和HindIII切断，将片段结合于双载体SBS4055的XhoI/HindIII位点(图10)。须知SBS4055含有来自菜豆的β-菜豆蛋白启动子/终止子(Slightom等人，1983，Proc.Natl.Acad.Sc.USA 801897-1901)，控制框内融合于D9 scFV抗体的PRS信号序列表达。质粒亦含有pat基因，赋予宿主植物有草铵膦抵抗性(Wohlleben等人，1988，Gene 7025-37)，利用来自欧芹的遍在蛋白启动子/终止子驱动(Kawalleck等人，1993，Plant.Mol.Bio.，21673-684)，供转化为土壤杆菌。Apo34是种子特异性克隆，把met/Apo AI原导向分泌通路，并与油质蛋白抗体D9框内融合，以助纯化。
Apo35Apo35(SEQ ID NO208)是种子优选克隆，其构建如图8所示。参见2图2，Apo35克隆包含驱动PRS/D9 scFV/Apo AI/KDEL(SEQ IDNO209)融合蛋白表达的种子优选启动子和终止子(菜豆蛋白)。D9ScFV/Apo AI使用烟草致病相关序列(PRS)信号肽，为表达而导向分泌通路(Sijmons等人，1990，Bio/technology，8217-221)，并使用KDEL保留信号(Munro和Pelham，1987，Cell 48899--907)把多肽保留于ER内。为构建此克隆，正向引物1200(SEQ ID NO188)(5’-GCAGCACTCGAGcaagttcCGGCATTTCT GGCAGCAAGA-3’)于ApoAI原开始，加KDEL序列。反向引物1208(SEQ ID NO210)(5’-AAGCTTTCA tagctcatctttCTGGGTGTTGAGCTTCTTAG-3’)于终止密码子之前，加KDEL序列，于终止密码子之后，加HindIII位点。这些引物针对的模板为Apo33质粒，含Apo AI原型，无内部XhoI位点和另外Met残基。PCR片段以XhoI切断，结合于pKS+的XhoI/EcoRV位点，产生质粒8-5。质粒8-5用XhoI和HindIII切断，结合于双载体SBS4055的XhoI/HindIII位点(图9)。须知SBS4055含有来自菜豆的β-菜豆蛋白启动子/终止子(Slightom等人，1983，Proc.Natl.Acad.Sc.USA 801897-1901)，控制框内融合D9scFV插段的PRS信号序列表达。质粒亦含有pat基因，赋予宿主植物有草铵膦抵抗性(Wohlleben等人，1988，Gene 7025-37)，利用来自欧芹的遍在蛋白启动子/终止子驱动(Kawalleck等人，1993，Plant.Mol.Bio.，21673-684)，供转化为土壤杆菌。Apo35为种子特异性克隆，把Apo AI导向分泌通路，保留于ER内，以油质蛋白D9scFV抗体纯化。
Apo36Apo36(SEQ ID NO211)是种子优选克隆，其构建如图11所示。参见2图2，Apo36克隆包含驱动PRS/D9 scFV/Apo AI原/KDEL(SEQ ID NO212)融合蛋白表达的种子优选启动子和终止子(菜豆蛋白)。D9 ScFV/Apo AI原使用烟草致病相关序列(PRS)信号肽，为表达而导向分泌通路(Sijmons等人，1990，Bio/technology，8217-221)，并使用KDEL保留信号(Munro和Pelham，1987，Cell 48899-907)把多肽保留于ER内。为构建此克隆，正向引物1200(SEQ IDNO188)(5’-GCAGCACTCGAGcaagttcCGGCATTTCTGGCAGCAAGA-3’)于Apo AI原开始，加XhoI位点和额外核苷酸，以方便框内克隆于klip8裂解序列。反向引物1208(SEQ IDNO210)(5’-AAGCTTTCAtagctcatcttt CTGGGTGTTGAGCTTCTTAG-3’)于终止密码子之前，加KDEL序列，于终止密码子之后，加HindIII位点。这些引物针对的模板为P-10质粒(图9)，含Apo AI原型，无内部XhoI位点。PCR片段以XhoI和HindIII切断，结合于pKS+的XhoI/EcoRV位点，产生质粒7-12。质粒7-12用XhoI和HindIII切断，结合于双载体SBS4055的XhoI/HindIII位点(图9)。须知SBS4055含有来自菜豆的β-菜豆蛋白启动子/终止子(Slightom等人，1983，Proc.Natl.Acad.Sc.USA 801897-1901)，控制框内融合D9 scFV插段的PRS讯号序列表达。质粒亦含有pat基因，赋予宿主植物有草铵膦抵抗性(Wohlleben等人，1988，Gene 7025-37)，利用来自欧芹的遍在蛋白启动子/终止子驱动(Kawalleck等人，1993，Plant.Mol.Bio.，21673-684)，供转化为土壤杆菌。Apo36为导向分泌通路的Apo AI原之种子特异性表达克隆，与油质蛋白抗体D9框内融合，因KDEL信号肽而累积于内质网内。
Apo37Apo37(SEQ ID NO213)是种子优选克隆，其构建如图12所示。参见2图2，Apo37克隆包含驱动PRS/D9 scFV/met/Apo AI/KDEL(SEQ ID NO214)融合蛋白表达之种子优选启动子和终止子(菜豆蛋白)。D9ScFV/met/Apo AI使用烟草致病相关序列(PRS)信号肽，为表达而导向分泌通路(Sijmons等人，1990，Bio/technology，8217-221)，并使用KDEL保留信号(Munro和Pelham，1987，Cell 48899-907)，把多肽保留在ER内。为构建此克隆，正向引物1203(SEQID NO173)(5’-GCAGCACCATGGATGAACCCCCCCAGAGCCCCTG-3’)在成熟Apo AI开始，加NcoI位点。反向引物1208(SEQ ID NO210)(5’-AAGCTTTCAtagctcatctttCTGGGTGTTGAGCTTCTTAG-3’)于终止密码子之前加KDEL序列，于终止密码子之后加HindIII位点。这些引物针对的模板为P-10质粒(图9)，含Apo AI原型，无内部XhoI位点。把PCR片段结合于pKS+质粒之EcoRV位点，产生质粒10-2。质粒用NcoI和HindIII切断，把片段结合于SBS4010载体BspHI/HindIII位点，产生质粒4010+10-2。质粒以XhoI和HindIII切断，把片段结合于双载体SBS4055之XhoI/HindIII位点(图9)。须知SBS4055含有来自菜豆的β-菜豆蛋白启动子/终止子(Slightom等人，1983，Proc.Natl.Acad.Sc.USA 801897-1901)，控制框内融合D9 scFV插段的PRS信号序列表达。质粒亦含有pat基因，赋予宿主植物草铵膦抵抗性(Wohlleben等人，1988，Gene 7025-37)，利用来自欧芹的遍在蛋白启动子/终止子驱动(Kawalleck等人，1993，Plant.Mol.Bio.，21673-684)，供转化成土壤杆菌。Apo37是把met/Apo AI导向分泌通路之克隆，且其与油质蛋白抗体D9框内融合，因KDEL信号肽而累积于内质网内。
Apo38Apo38(SEQ ID NO215)是种子优选克隆，其构建如图12所示。参见2图2，Apo38克隆包含驱动PRS/D9 scFV/met/Apo AI原/KDEL(SEQ ID NO216)融合蛋白表达之种子优选启动子和终止子(菜豆蛋白)。D9ScFV/met/Apo AI原使用烟草致病相关序列(PRS)信号肽，为表达而导向分泌通路(Sijmons等人，1990，Biotechnology，8217-221)，并使用KDEL保留信号(Munro和Pelham，1987，Cell 48899-907)，把多肽保留在ER内。为构建此克隆，正向引物1201(SEQID NO177)(5’-GCAGCACCATGGggCGGCATTTCTGGCAGCAAGATG-3’)在成熟Apo AI开始，加NcoI位点。反向引物1208(SEQ ID NO210)(5’-AAGCTTTCAtagctcatctttCTGGGTGTTGAGCTTCTTAG-3’)于终止密码子之前加KDEL序列，于终止密码子之后加HindIII位点。这些引物针对的模板为P-10质粒(图9)，含Apo AI原型，无内部XhoI位点。把PCR片段结合于pKS+质粒之EcoRV位点，产生质粒9-2。质粒用NcoI和HindIII切断，把片段结合于SBS4010载体BspHI/HindIII位点，产生质粒4010+9-2。质粒以XhoI和HindIII切断，把片段结合于双载体SBS4055之XhoI/HindIII位点(图9)。须知SBS4055含有来自菜豆的β-菜豆蛋白启动子/终止子(Slightom等人，1983，Proc.Natl.Acad.Sc.USA 801897-1901)，控制框内融合D9 scFV插段的PRS信号序列表达。质粒亦含有pat基因，赋予宿主植物草铵膦抵抗性(Wohlleben等人，1988，Gene 7025-37)，利用来自欧芹的遍在蛋白启动子/终止子驱动(Kawalleck等人，1993，Plant.Mol.Bio.，21673-684)，供转化成土壤杆菌。Apo38是把met/Apo AI原导向分泌通路之克隆，与油质蛋白抗体D9框内融合，因KDEL信号肽而累积于内质网内。
Apo39
Apo39(SEQ ID NO217)是种子优选克隆，其构建如图13所示。参见2图2，Apo39克隆包含驱动PRS/D9 scFV/klip8/Apo AI(SEQID NO218)融合蛋白表达之种子优选启动子和终止子(菜豆蛋白)。D9ScFV/klip8/Apo AI使用烟草致病相关序列(PRS)信号肽，为表达而导向分泌通路(Sijmons等人，1990，Bio/technology，8217-221)，并使用KDEL保留信号(Munro和Pelham，1987，Cell 48899--907)，把多肽保留在ER内。此克隆有klip8裂解序列(SEQ ID NO143)，以方便融合蛋白用凝乳酶裂解。为构建此克隆，正向引物1207(SEQ ID NO219)(5’-GCAGCAGTCGACtATGGCTGAGATCACCCGCATTC-3’)在起始密码子加SalI位点。反向引物1206(SEQ ID NO174)(5’-GTGGTGAAGCTTTCACTGGGTGTTGAGCTTCTTAGTGTACTCCTCcAGAGCG-3’)于终止密码子之后加HindIII位点，并加沉默(扩增klip8的起始处)突变以除去第二XhoI位点。PCR反应用之模板为质粒Apo27(图8(A))，PCR产物以SalI和HindIII切断，结合于pKS+，产生质粒13-1。质粒用SalI和HindIII切断，结合于质粒SBS4055之XhoI/HindIII位点(图9)。须知SBS4055含有来自菜豆的β-菜豆蛋白启动子/终止子(Slightom等人，1983，Proc.Natl.Acad.Sc.USA 801897-1901)，控制框内融合D9 scFV插段的PRS信号序列表达。质粒亦含有pat基因，赋予宿主植物草铵膦抵抗性(Wohlleben等人，1988，Gene7025-37)，利用来自欧芹的遍在蛋白启动子/终止子驱动(Kawalleck等人，1993，Plant.Mol.Bio.，21673-684)，供转化成土壤杆菌。Apo39是把D9scFV/klip8/Apo AI导向分泌通路之种子优选表达克隆，使用对油体上的油质蛋白具有亲和性之D9 scFV抗体，达成Apo AI纯化。使用把klip8位点裂解的凝乳酶，可将蛋白裂解。
Apo40Apo40(SEQ ID NO220)是种子优选克隆，其构建如图13所示。参见2图2，Apo40克隆包含驱动PRS/D9 scFV/klip8/Apo AI原(SEQ ID NO221)融合蛋白表达之种子优选启动子和终止子(菜豆蛋白)。D9 ScFV/klip8/Apo AI原使用烟草致病相关序列(PRS)信号肽，为表达而导向分泌通路(Sijmons等人，1990，Bio/technology，8217-221)，此克隆有klip8裂解序列(SEQ ID NO143)，以方便融合蛋白用凝乳酶裂解。为构建此克隆，正向引物1207(SEQ ID NO219)(5’-GCAGCAGTCGACtATGGCTGAG ATCACCCGCATTC-3’)序列，并于起始密码子加SalI位点。反向引物1206(SEQ ID NO174)(5’-GTGGTGAAGCTTTCACTGGGTGTTGAGCTTCTTAGTGTACTCCTCcAGAGCG-3’)在终止密码子之后加HindIII位点，并加沉默突变，以除去第二XhoI位点。PCR反应用之模板为质粒Apo27(图8(A))，PCR产物以SalI和HindIII切断，结合于pKS+，产生质粒14-5。质粒用SalI和HindIII切断，结合于质粒SBS4055之XhoI/HindIII位点(图9)。须知SBS4055含有来自菜豆的β-菜豆蛋白启动子/终止子(Slightom等人，1983，Proc.Natl.Acad.Sc.USA 801897-1901)，控制框内融合D9scFV插段的PRS信号序列表达。质粒亦含有pat基因，赋予宿主植物草铵膦抵抗性(Wohlleben等人，1988，Gene 7025-37)，利用来自欧芹的遍在蛋白启动子/终止子驱动(Kawalleck等人，1993，Plant.Mol.Bio.，21673-684)，供转化成土壤杆菌。Apo40是把D9 scFV/klip8/Apo AI原导向分泌通路之种子优选的表达克隆，使用对油体上油质蛋白具有亲和性的D9 scFV抗体，达成Apo AI原之纯化。使用将klip8位点裂解的凝乳酶，可将蛋白裂解。
Apo41Apo41(SEQ ID NO222)是种子优选克隆，其构建如图14所示。参见2图2，Apo41克隆包含驱动PRS/D9 scFV/klip8/met/Apo AI(SEQ ID NO223)融合蛋白表达之种子优选启动子和终止子(菜豆蛋白)。D9 ScFV/klip8/met/Apo AI使用烟草致病相关序列(PRS)信号肽，为表达而导向分泌通路(Sijmons等人，1990，Bio/technology，8217-221)。此克隆具有klip8裂解序列(SEQ ID NO143)，以方便融合蛋白以凝乳酶裂解。为构建此克隆，正向引物1207(SEQ ID NO219)(5’-GCAGCAGTCGACtATGGC TGAGATCACCC GCATTC-3’)把klip8序列开始扩增，于起始密码子加SalI位点。反向引物1206(SEQ IDNO174)(5’-GTGGTGAAGCTTTCACTGGGTGTTGAGCTTCTTAGTGTACTCCTCcAGAGCG-3’)于终止密码子后加HindIII位点，并加沉默突变，除去第二XohI位点。PCR反应用模板为质粒Apo25(图6)。PCR产物以SalI和HindIII切断，结合于pKS+内，产生质粒11-1。质粒以SalI和HindIII切断，结合于双载体SBS4055的XhoI/HindIII位点(图9)。须知SBS4055含有来自菜豆的β-菜豆蛋白启动子/终止子(Slightom等人，1983，Proc.Natl.Acad.Sc.USA 801897-1901)，控制框内融合D9 scFV插段的PRS信号序列表达。质粒亦含有pat基因，赋予宿主植物以草铵膦抵抗性(Wohlleben等人，1988，Gene 7025-37)，利用来自欧芹的遍在蛋白启动子/终止子驱动(Kawalleck等人，1993，Plant.Mol.Bio.，21673-684)，供转化为土壤杆菌。Apo41是导向分泌通路的D9scFV/klip8/met/Apo AI的种子优选表达克隆。使用对油体上的油质蛋白具有亲和性的D9 scFV抗体，达成met/Apo AI的纯化。使用将klip8位点裂解的凝乳酶，可将蛋白裂解。
Apo42Apo42(SEQ ID NO224)是种子优选克隆，其构建如图14所示。参见2图2，Apo42克隆包含驱动PRS/D9 scFV/klip8/met/Apo AI原(SEQ ID NO225)融合蛋白表达之种子优选启动子和终止子(菜豆蛋白)。D9 ScFV/klip8/met/Apo AI原使用烟草致病相关序列(PRS)信号肽，为表达而导向分泌通路(Sijmons等人，1990，Bio/technology，8217-221)。此克隆具有klip8裂解序列(SEQ ID NO143)，以方便融合蛋白以凝乳酶裂解。为构建此克隆，正向引物1207(SEQ ID NO219)(5’-GCAGCAGTCGACtATGG CTGAGATCACCC GCATTC-3’)把klip8序列开始扩增，于起始密码子加SalI位点。反向引物1206(SEQ IDNO174)(5’-GTGGTGAAGCTTTCACTGGGTGTTGAGCTTCTTAGTGTACTCCTCcAGAGCG-3’)于终止密码子后加HindIII位点，并加沉默突变，除去第二XohI位点。PCR反应用模板为质粒Apo26(图7)。PCR产物以SalI和HindIII切断，结合于pKS+内，产生质粒12-1。质粒以SalI和HindIII切断，结合于双载体SBS4055的XhoI/HindIII位点(图9)。须知SBS4055含有来自菜豆的β-菜豆蛋白启动子/终止子(Slightom等人，1983，Proc.Natl.Acad.Sc.USA 801897-1901)，控制框内融合D9scFV插段的PRS信号序列表达。质粒亦含有pat基因，赋予宿主植物以草铵膦抵抗性(Wohlleben等人，1988，Gene 7025-37)，利用来自欧芹的遍在蛋白启动子/终止子驱动(Kawalleck等人，1993，Plant.Mol.Bio.，21673-684)，供转化为土壤杆菌。Apo42是导向分泌通路的D9 scFV/klip8/met/Apo AI原的种子优选表达克隆。使用对油体上的油质蛋白具有亲和性的D9scFV抗体，达成met/Apo AI的纯化。使用将klip8位点裂解的凝乳酶，可将蛋白裂解。
Apo43Apo43(SEQ ID NO226)是种子优选克隆，其构建如图13所示。参见2图2，Apo43克隆包含驱动PRS/D9 scFV/klip8/Apo AI/KDEL(SEQ ID NO227)融合蛋白表达之种子优选启动子和终止子(菜豆蛋白)。D9 ScFV/klip8/Apo AI使用烟草致病相关序列(PRS)信号肽，为表达而导向分泌通路(Sijmons等人，1990，Bio/technology，8217-221)，并使用KDEL保留信号(Munro和Pelham，1987，Cell 48899-907)，把多肽保留在ER内。此克隆具有klip8裂解序列(SEQ ID NO143)，以方便融合蛋白以凝乳酶裂解。为构建此克隆，正向引物1207(SEQ ID NO219)(5’-GCAGCAGTCGACtATGGC TGAGATCACCCGCATTC-3’)把klip8序列开始扩增，于起始密码子加SalI位点。反向引物1208(SEQ ID NO210)(5’-AAGCTTTCAtagctcatctttCTGGGTGTTGAGCTTCTTAG-3’)于终止密码子前加KDEL序列，于终止密码子后加HindIII位点。PCR反应用模板为质粒Apo27(图8(A))。PCR产物以SalI和HindIII切断，结合于pKS+内，产生质粒17-1。质粒以SalI和HindIII切断，结合于质粒SBS4055的XhoI/HindIII位点(图9)。须知SBS4055含有来自菜豆的β-菜豆蛋白启动子/终止子(Silghtom等人，1983，Proc.Natl.Acad.Sc.USA 801897-1901)，控制框内融合D9 scFV插段的PRS信号序列表达。质粒亦含有pat基因，赋予宿主植物以草铵膦抵抗性(Wohlleben等人，1988，Gene 7025-37)，利用来自欧芹的遍在蛋白启动子/终止子驱动(Kawalleck等人，1993，Plant.Mol.Bio.，21673-684)，供转化为土壤杆菌。Apo43是导向分泌通路的D9 scFV/klip8/Apo AI/KDEL的种子优选表达克隆。Apo43由于KDEL信号肽而累积于ER内。使用对油体上的油质蛋白具有亲和性的D9 scFV抗体，达成Apo AI的纯化。使用将klip8位点裂解的凝乳酶，可将蛋白裂解。
Apo44Apo44(SEQ ID NO228)是种子优选克隆，其构建如图13所示。参见2图2，Apo44克隆包含驱动PRS/D9 scFV/klip8/Apo AI原/KDEL(SEQ ID NO229)融合蛋白表达之种子优选启动子和终止子(菜豆蛋白)。D9 ScFV/klip8/Apo AI原/KDEL使用烟草致病相关序列(PRS)信号肽，为表达而导向分泌通路(Sijmons等人，1990，Bio/technology，8217-221)，使用KDEL保留信号(Munro和Pelham，1987，Cell 48899--907)，把多肽保留在ER内。此克隆具有klip8裂解序列(SEQ ID NO143)，以方便融合蛋白以凝乳酶裂解。为构建此克隆，正向引物1207(SEQ ID NO219)(5’-GCAGCAGTCGACtATGGCTGAGATCACCC GCATTC-3’)序列于起始密码子加SalI位点。反向引物1208(SEQ ID NO210)(5’-AAGCTTTCAtagctcatcttt CTGGGTGTTGAGCTTCTTAG-3’)于终止密码子前加KDEL序列，于终止密码子后加HindIII位点。PCR反应用模板为质粒Apo28(图9)。PCR产物以SalI和HindIII切断，结合于pKS+内，产生质粒18-2。质粒以SalI和HindIII切断，结合于质粒SBS4055的XhoI/HindIII位点(图9)。须知SBS4055含有来自菜豆的β-菜豆蛋白启动子/终止子(Slightom等人，1983，Proc.Natl.Acad.Sc.USA 801897-1901)，控制框内融合D9 scFV插段的PRS信号序列表达。质粒亦含有pat基因，赋予宿主植物以草铵膦抵抗性(Wohlleben等人，1988，Gene 7025-37)，利用来自欧芹的遍在蛋白启动子/终止子驱动(Kawalleck等人，1993，Plant.Mol.Bio.，21673-684)，供转化为土壤杆菌。Apo44是导向分泌通路的D9 scFV/klip8/Apo AI原/KDEL的种子优选表达克隆。Apo44由于KDEL信号肽而累积于ER内。使用对油体上的油质蛋白具有亲和性的D9 scFV抗体，达成Apo AI原的纯化。使用将klip8位点裂解的凝乳酶，可将蛋白裂解。
Apo45Apo45(SEQ ID NO230)是种子优选克隆，其构建如图14所示。参见2图2，Apo45克隆包含驱动PRS/D9 scFV/klip8/met/ApoAI/KDEL(SEQ ID NO231)融合蛋白表达之种子优选启动子和终止子(菜豆蛋白)。D9 ScFV/klip8/met/Apo AI使用烟草致病相关序列(PRS)信号肽，为表达而导向分泌通路(Sijmons等人，1990，Bio/technology，8217-221)，使用KDEL保留信号(Munro和Pelham，1987，Cell 48899--907)，把多肽保留在ER内。此克隆具有klip8裂解序列(SEQ ID NO143)，以方便融合蛋白以凝乳酶裂解。为构建此克隆，正向引物1207(SEQ ID NO219)(5’-GCAGCAGTCGACtATGGCTGAGATCACCC GCATTC-3’)把klip8序列开始扩增，于起始密码子加SalI位点。反向引物1208(SEQ ID NO210)(5’-AAGCTTTCAtagctcatctttCTGGGTGTTGAGCTTCTTAG-3’)于终止密码子前加KDEL序列，于终止密码子后加HindIII位点。PCR反应用模板为质粒Apo25(图6)。PCR产物以SalI和HindIII切断，结合于pKS+内，产生质粒15-1。质粒以SalI和HindIII切断，结合于双载体SBS4055的XhoI/HindIII位点(图9)。须知SBS4055含有来自菜豆的β-菜豆蛋白启动子/终止子(Slightom等人，1983，Proc.Natl.Acad.Sc.USA 801897-1901)，控制框内融合D9 scFV插段的PRS信号序列表达。质粒亦含有pat基因，赋予宿主植物以草铵膦抵抗性(Wohlleben等人，1988，Gene 7025-37)，利用来自欧芹的遍在蛋白启动子/终止子驱动(Kawalleck等人，1993，Plant.Mol.Bio.，21673-684)，供转化为土壤杆菌。Apo45是导向分泌通路的D9 scFV/klip8/met/Apo AI/KDEL的种子优选表达克隆。Apo45因KDEL信号肽而累积于ER内。使用对油体上的油质蛋白具有亲和性的D9 scFV抗体，达成Apo AI的纯化。使用将klip8位点裂解的凝乳酶，可将蛋白裂解。
Apo46Apo46(SEQ ID NO232)是种子优选克隆，其构建如图14所示。参见2图2，Apo46克隆包含驱动PRS/D9 scFV/klip8/met/Apo AI原/KDEL(SEQ ID NO233)融合蛋白表达之种子优选启动子和终止子(菜豆蛋白)。D9 ScFV/klip8/met/Apo AI原使用烟草致病相关序列(PRS)信号肽，为表达而导向分泌通路(Sijmons等人，1990，Bio/technology，8217-221)，使用KDEL保留信号(Munro和Pelham，1987，Cell 48899-907)，把多肽保留在ER内。此克隆具有klip8裂解序列(SEQ ID NO143)，以方便融合蛋白以凝乳酶裂解。为构建此克隆，正向引物1207(SEQ ID NO219)(5’-GCAGCAGTCGACtATGGCTGAGATCACCC GCATTC-3’)把klip8序列开始扩增，于起始密码子加SalI位点。反向引物1208(SEQ ID NO210)(5’-AAGCTTTCAtagctcatctttCTGGGTGTTGAGCTTCTTAG-3’)于终止密码子前加KDEL序列，于终止密码子后加HindIII位点。PCR反应用模板为质粒Apo26(图7)。PCR产物以SalI和HindIII切断，结合于pKS+内，产生质粒16-4。质粒以SalI和HindIII切断，结合于双载体SBS4055的XhoI/HindIII位点(图9)。须知SBS4055含有来自菜豆的β-菜豆蛋白启动子/终止子(Slightom等人，1983，Proc.Natl.Acad.Sc.USA 801897-1901)，控制框内融合D9 scFV插段的PRS信号序列表达。质粒亦含有pat基因，赋予宿主植物以草铵膦抵抗性(Wohlleben等人，1988，Gene 7025-37)，利用来自欧芹的遍在蛋白启动子/终止子驱动(Kawalleck等人，1993，Plant.Mol.Bio.，21673-684)，供转化为土壤杆菌。Apo46是导向分泌通路的D9 scFV/klip8/met/Apo AI原的种子优选表达克隆。使用对油体上的油质蛋白具有亲和性的D9 scFV抗体，达成Apo AI的纯化。使用将klip8位点裂解的凝乳酶，可将蛋白裂解。
Apo47Apo47(SEQ ID NO234)是种子优选克隆，其构建如图15所示。参见2图2，Apo47克隆包含驱动玉米油质蛋白/klip8/met/Apo AI(SEQ ID NO235)表达之种子优选启动子和终止子(核网)。此构建体具有klip8裂解序列(SFQ ID NO143)，以方便融合蛋白用凝乳酶裂解。为构建此克隆，使用正向引物1226(5’-GCAGCACCATGGCTGATCACCACCG-3’)(SEQ ID NO236)把来自pSBS2377的玉米油质蛋白的编码序列扩增，于基因开始加NcoI位点，组合反向引物1227(5’-GTGGTGAAGCTTAGACCCCTGCGCC-3’)(SEQ ID NO237)，除去基因的终止密码子，加HindIII位点，以协助与klip8/met/Apo AI产生框内翻译融合。来自Apo25的klip8/met/Apo AI的编码序列，使用正向引物1228(5’GCAGCAAAGCTTATGGCTGAGATCAC-3’)(SEQ ID NO238)扩增，并在基因起始处加HindIII位点。反向引物1229(5’-GTGTGGGATCCTCACTGGGTGTTG-3’)(SEQ ID NO239)于终止密码子后加BamHI位点。含玉米油质蛋白cDNA和klip8/met/Apo AI的PCR片段，结合于Topo克隆载体(Invitrogen)的EcoRI位点。质粒MzOleo以限制性酶NcoI和HindIII切断。质粒klip8/met/Apo AI以HindIII和BamHI切断。MzOleo和klip8/met/Apo AI的片段一同结合于质粒SBS5709的NcoI和BamHI位点，产生质粒Apo47。pSBS5709含有来自WO 01/16340的核网启动子/终止子，旁侧多种克隆位点。pSBS5709亦含有pmi基因(Miles等人，1984，Gene 2141-48)，为磷酸甘露糖异构酶，得以正面选择含选择培养基的甘露糖。pmi基因是在来自欧芹的遍在蛋白启动子/终止子驱动(Kawalleck等人，1993，Plant.Mol.Bio.，21673-684)，供转化为土壤杆菌。Apo47是把玉米油质蛋白/klip8/met/Apo AI导向油体的种子特异性克隆，并使用klip8裂解序列纯化。
实施例2土壤杆菌和拟南芥转化全部实验使用拟南芥(Arabidopsis thaliana cv.Columbia(C24))。种子播在4时盆内土壤混合物(三分之二Redi土和三分之一珠岩，pH＝6.7)或Lehle种子公司所供应拟南芥土壤混合物(珠岩、蛭石、泥媒、绿土陶，pH＝5.5)的表面。让幼苗成长到6-8叶的花形阶段，直径约2.5厘米。此等幼苗转植到含上述土壤混合物的4时盆，覆盖以窗帘材料，有五个1厘米直径洞孔，裁成网；四角各一个，中央一个。盆在4℃棚内放四天，供冷处理，随后移到24℃成长室内，在约150μE和50％相对湿度，光照不停。植物每隔2-3天浇水，每周施肥1％Peters 20-20-20。各盆含5株植物。植物到达约2厘米高时，把主茎剪断，促使第二和第三茎成长。剪掉主茎4-5天后，植物准备接受土壤杆菌感染，质粒转化为电竞争性土壤杆菌EHA101。盆连拟南芥植物倒转，以再悬浮过夜的500毫升土壤杆菌培养物(含标的植物转化载体)感染20秒。关键在于土壤杆菌含5％蔗糖和0.05％表面活性剂Silwet L-77(Lehle Seeds)。盆随即覆盖透明塑料棚达24小时，以维持较高湿度。让植物成长成熟，收获种子(未转化和转化)。为选择转基因株，将推定转化种子杀菌，以70％乙醇快洗，再20％商业用漂白粉洗15分钟，然后以ddH2O淋洗至少4次。约1000颗经杀菌的种子，与0.6％顶级琼脂混合，均匀分布于半强MS板上(Murashige和Skoog，1962，Physiologia Plantarum 15473-497)，含0.5％蔗糖和80μM除草剂草铵膦(PPT)DL。板再放进成长室内，在24℃的光照是8小时暗和16小时亮。七至十天后，推定转基因种子绿了，继续成长，而未转化幼苗则惨白。生根后，推定转基因幼苗个别转移至盆(个别植物每隔三天浇水，每隔五天施肥1％Peters 20-20-20)，让其成长成熟。盆覆盖转基因塑料棚三天，以保护敏感性幼苗。七天后，幼苗覆盖Lehle种子公司的种子收集器，以防种子散落损失。分别收获此等转基因植物的种子，准备供分析。
全叶提取物制备拟南芥叶用液氮冷冻，在1.5毫升微离心管内，用钻磨。加200-250μL 0.5M Tris-HCl，pH 7.5，把样品倒在冰上。加20％SDS至最后浓度2％，样品煮沸5分钟，提取物在微离心管内以最大速度旋转5分钟。液体移到另一微离心管，在-20℃储存。可溶性蛋白使用BCA蛋白质测定法(Pierce)量化，在15％SDS-PAGE上分析，接着利用蛋白质印迹法。使用抗Apo AI或抗GFP兔抗血清，作为主要抗体；而使用抗兔IgG〔H+L〕-Ap去轭(Bio-Rad)作为次级抗体。
全种子提取物制备取大约40粒拟南芥种子(T2种子)，在微离心管内的50μL缓冲液(50mM Tris pH 7.5)中，使用Stir-Pak实验室混合器研磨。随即于样品加20％SDS至最后浓度为2％，样品煮沸5分钟，以最大速度离心5分钟。为加载于SDS-PAGE凝胶上，于样品加SDS-PAGE 2X加载缓冲液(100mM Tris pH 6.8，20％丙三醇，4％SDS，2mg/mL，溴酚蓝，200mMDTT)和1M DTT，煮沸5分钟，以最大速度离心2分钟。
实施例3蛋白质印迹法分析载脂蛋白表达组成型表达Apo17参见实施例1，Apo17(SEQ ID NO27)是成熟Apo AI和GFP间之融合蛋白。使用遍在蛋白启动子和终止子，供构建体之组成型表达。蛋白质印迹分析(图16(A))使用多克隆Apo AI抗体，于12个克隆当中的9个内，在全叶提取物中，检测到很低量(占总叶蛋白的0.1％以下)之Apo AI/GFP融合蛋白，分子量大约55kDa。然而Apo17融合蛋白的明显表达(占全种子蛋白的至少1％)，在受测试的12克隆内有11个，于全种子提取物内检测得(图16(B))，大约为55kDa。
Apo18a参见实施例1，Apo18(SEQ ID NO29)是成熟Apo AI原和GFP间之融合蛋白。使用遍在蛋白启动子和终止子，供构建体表达。蛋白质印迹分析(图17(A))使用多克隆Apo AI抗体，于12当中的3个克隆内，在全叶提取物中，检测到很低量(占总叶蛋白的0.1％以下)之ApoAI原/GFP融合蛋白，分子量大约56kDa。然而Apo18融合蛋白的明显表达(占全种子蛋白的至少1％)，在受测试的全部克隆内，于全种子提取物内检测得(图17(B))，大约为56kDa。
Apo19参见实施例1，Apo19(SEQ ID NO31)是Apo AI和GFP间之融合蛋白。使用遍在蛋白启动子和终止子，供构建体表达，并使用PRS信号肽，供融合蛋白的表达导向ER。蛋白质印迹分析(图18(A))使用多克隆Apo AI抗体，于12当中的10个克隆内，在全叶提取物中，检测到很低量(占总叶蛋白的0.1％以下)之Apo AI/GFP融合蛋白，分子量大约58kDa。然而Apo19融合蛋白的明显表达(占全种子蛋白的至少1％)，在受测试的18个克隆内有17个，于全种子提取物内检测得(图18(B))，大约为58kDa。
Apo20参见实施例1，Apo20(SEQ ID NO35)是Apo AI原和GFP间之融合蛋白。使用遍在蛋白启动子和终止子，供构建体表达，并使用PRS信号肽，供融合蛋白的表达导向ER。蛋白质印迹分析(图19(A))使用多克隆Apo AI抗体，于受测试12个克隆当中的3个内，在全叶提取物中，检测到很低量(占总叶蛋白的0.1％以下)之Apo AI原/GFP融合蛋白，分子量大约59kDa。然而Apo20融合蛋白的明显表达(占全种子蛋白的至少1％)，在受测试的18个克隆内有16个，于全种子提取物内检测得(图19(B))，大约为59kDa。
种子特异性表达Apo10参见实施例1，Apo10(SEQ ID NO10)是成熟Apo AI和GFP间之融合蛋白。使用菜豆蛋白启动子和终止子，供构建体的种子特异性表达。蛋白质印迹分析(图20(A))使用多克隆GFP抗体，在受测试的10之7克隆中，检测全种子提取物内的Apo AI/GFP融合蛋白，分子量大约55kDa。
Apo11参见实施例1，Apo11(SEQ ID NO16)是成熟Apo AI原和GFP间之融合蛋白。使用菜豆蛋白启动子和终止子，供构建体的种子特异性表达。蛋白质印迹分析(图20(B))使用多克隆GFP抗体，在受测试的14之10克隆中，检测全种子提取物内的Apo AI原/GFP融合蛋白，分子量大约56kDa。
Apo12参见实施例1，Apo12(SEQ ID NO19)是油质蛋白成熟Apo AI和GFP间之融合蛋白。使用菜豆蛋白启动子和终止子，供构建体的种子特异性表达。蛋白质印迹分析(图21(A))使用多克隆GFP抗体，在受测试的全部17克隆中，检测全种子提取物内的Apo AI/GFP融合蛋白，分子量大约74kDa。
Apo13参见实施例1，Apo13(SEQ ID NO21)是油质蛋白成熟Apo AI原和GFP间之融合蛋白。使用菜豆蛋白启动子和终止子，供构建体的种子特异性表达。蛋白质印迹分析(图21(B))使用多克隆GFP抗体，在受测试的全部18克隆中，检测全种子提取物内的油质蛋白Apo AI原/GFP融合蛋白，分子量大约75kDa。
Apo15参见实施例1，Apo 15(SEQ ID NO23)是成熟Apo AI和GFP间之融合蛋白。使用菜豆蛋白启动子和终止子，供构建体的种子特异性表达，并使用PRS信号肽，供融合蛋白在分泌系统进行导向表达。蛋白质印迹分析(图22(A))使用多克隆GFP抗体，在受测试10之9克隆中，检测全种子提取物内的Apo AI/GFP融合蛋白，分子量大约58kDa。
Apo16参见实施例1，Apo16(SEQ ID NO25)是成熟Apo AI原和GFP间之融合蛋白。使用菜豆蛋白启动子和终止子，供构建体的种子特异性表达，并使用PRS信号肽，供融合蛋白对分泌通路之导向表达。蛋白质印迹分析(图22(B))使用多克隆GFP抗体，在受测试13之10克隆中，检测全种子提取物内的Apo AI原/GFP融合蛋白，分子量大约59kDa。
Apo21参见实施例1，Apo21(SEQ ID NO37)是Apo AI。使用菜豆蛋白启动子和终止子，供构建体的种子特异性表达。蛋白质印迹分析(图23(A))使用多克隆Apo AI抗体，在全种子提取物内检测Apo AI蛋白。预计分子量大约28kDa。在受测试的12克隆中，以Apo AI抗体检测许多不同蛋白，范围大约25kDa向上至55kDa。可知Apo AI的表达有损植物健康(即发育不良的长角果，和不结籽)。
Apo22参见实施例1，Apo22(SEQ ID NO41)是Apo AI原。使用菜豆蛋白启动子和终止子，供构建体的种子特异性表达。蛋白质印迹分析(图23(B))使用多克隆Apo AI抗体，在全种子提取物内检测Apo AI蛋白。预计分子量大约29kDa。在受测试的6克隆中，以Apo AI抗体检测许多不同蛋白，范围大约25kDa向上至55kDa。克隆22-3具有适当分子量之蛋白。可知Apo AI原的表达，与表达构建体Apo21、Apo29和Apo30对Apo23之植物健康相比较，对具有中间表型的植物健康有损。
Apo23参见实施例1，Apo23(SEQ ID NO44)是油质蛋白和Apo AI间之融合蛋白。使用菜豆蛋白启动子和终止子，供构建体的种子特异性表达。蛋白质印迹分析(图24(A))使用多克隆Apo AI抗体，在受测试5之4克隆中，于全种子提取物内检测油质蛋白/Apo AI融合蛋白，分子量大约47kDa。
Apo24参见实施例1，Apo24(SEQ ID NO46)是油质蛋白和Apo AI原间之融合蛋白。使用菜豆蛋白启动子和终止子，供构建体的种子特异性表达。蛋白质印迹分析(图24(B))使用多克隆Apo AI抗体，在受测试全部7克隆中，于全种子提取物内检测油质蛋白/Apo AI融合蛋白，分子量大约48kDa。
Apo25参见实施例1，Apo25(SEQ ID NO48)是油质蛋白和Apo AI(+Met)间之融合蛋白，有klip8裂解序列把二成份分开。使用菜豆蛋白启动子和终止子，供构建体的种子特异性表达。蛋白质印迹分析(图25(A))使用多克隆Apo AI抗体，在受测试全部4克隆中，于全种子提取物内检测油质蛋白-klip8-Apo AI(+Met)融合蛋白，分子量大约51kDa。
Apo26参见实施例1，Apo26(SEQ ID NO51)是油质蛋白和Apo AI原(+Met)间之融合蛋白，有klip8裂解序列把二成份分开。使用菜豆蛋白启动子和终止子，供构建体的种子特异性表达。蛋白质印迹分析(图25(B))使用多克隆Apo AI抗体，在受测试全部11克隆中，于全种子提取物内检测油质蛋白-klip8-Apo AI原(+Met)融合蛋白，分子量大约52kDa。
Apo28参见实施例1，Apo28(SEQ ID NO60)是油质蛋白和Apo AI原间之融合蛋白，有klip8裂解序列把二成份分开。使用菜豆蛋白启动子和终止子，供构建体的种子特异性表达。蛋白质印迹分析(图26(A))使用多克隆Apo AI抗体，在受测试全部7克隆中，于全种子提取物内检测油质蛋白-klip8-Apo AI原融合蛋白，分子量大约52kDa。
Apo29参见实施例1，Apo29(SEQ ID NO63)是Apo AI。使用菜豆蛋白启动子和终止子，供构建体之种子特异性表达，并使用PRS信号肽，供蛋白对分泌通路之导向表达。蛋白质印迹分析(图26(B))使用多克隆Apo AI抗体，在全种子提取物内检测Apo AI蛋白。预计分子量大约31kDa。在受测试的10克隆中，只有一克隆检测到蛋白，惟分子量在37kDa范围。须知Apo AI的表达有损植物健康(即发育不良的长角果，和不结籽)。
Apo30
参见实施例1，Apo30(SEQ ID NO65)是Apo AI原。使用菜豆蛋白启动子和终止子，供构建体之种子特异性表达，并使用PRS信号肽，供融合蛋白对分泌通路之导向表达。蛋白质印迹分析(图27)使用多克隆Apo AI抗体，在全种子提取物内检测Apo AI蛋白。预计分子量大约32kDa。在受测试的13克隆中，有许多不同蛋白检知具有Apo AI抗体，范围大约25kDa上至55kDa。须知Apo AI原的表达有损植物健康(即发育不良的长角果，和不结籽)。
Apo32参见实施例1，Apo32(SEQ ID NO69)是D9scFV抗体和ApoAI原间之融合蛋白。使用菜豆蛋白启动子和终止子，供构建体的种子特异性表达，并使用PRS信号肽，供融合蛋白对分泌通路之导向表达。蛋白质印迹分析(图28(A))使用多克隆Apo AI抗体，在受测试全部5克隆中，于全种子提取物内检测D9 scFV-Apo AI原融合蛋白，分子量大约59kDa。
Apo33参见实施例1，Apo33(SEQ ID NO71)是D9 scFV抗体和ApoAI(+met)间之融合蛋白。使用菜豆蛋白启动子和终止子，供构建体的种子特异性表达，并使用PRS信号肽，供融合蛋白对分泌通路之导向表达。蛋白质印迹分析(图28(B))使用多克隆Apo AI抗体，在受测试8之1克隆中，于全种子提取物内检测D9 scFV-Apo AI(+met)融合蛋白，分子量大约59kDa。
Apo34参见实施例1，Apo34(SEQ ID NO73)是D9 scFV抗体和ApoAI原(+met)间之融合蛋白。使用菜豆蛋白启动子和终止子，供构建体的种子特异性表达，并使用PRS信号肽，供融合蛋白对分泌通路之导向表达。蛋白质印迹分析(图29)使用多克隆Apo AI抗体，在受测试7之6克隆中，于全种子提取物内检测D9 scFV-Apo AI原(+met)融合蛋白，分子量大约59kDa。
Apo36参见实施例1，Apo36(SEQ ID NO78)是D9 scFV抗体和ApoAI原间之融合蛋白。使用菜豆蛋白启动子和终止子，供构建体的种子特异性表达，并使用PRS信号肽，供融合蛋白对分泌通路之导向表达，又使用KDEL保留信号以保留多肽于ER内。蛋白质印迹分析(图30(A))使用多克隆Apo AI抗体，在受测试的全部13克隆中，于全种子提取物内检测D9 scFV-Apo AI原-KDEL融合蛋白，分子量大约60kDa。
Apo37参见实施例1，Apo37(SEQ ID NO80)是D9 scFV抗体和ApoAI(+met)间之融合蛋白。使用菜豆蛋白启动子和终止子，供构建体的种子特异性表达，并使用PRS信号肽，供融合蛋白对分泌通路之导向表达，又使用KDEL保留信号以保留多肽于ER内。蛋白质印迹分析(图30(B))使用多克隆Apo AI抗体，在受测试的全部15克隆中，于全种子提取物内检测D9 scFV-Apo AI(+met)-KDEL融合蛋白，分子量大约59kDa。
Apo38参见实施例1，Apo38(SEQ ID NO82)是D9 scFV抗体和ApoAI原(+met)间之融合蛋白。使用菜豆蛋白启动子和终止子，供构建体的种子特异性表达，并使用PRS信号肽，供融合蛋白对分泌通路之导向表达，又使用KDEL保留信号以保留多肽于ER内。蛋白质印迹分析(图31A图)使用多克隆Apo AI抗体，在受测试的11之9克隆中，于全种子提取物内检测D9 scFV-Apo AI原(+met)-KDEL融合蛋白，分子量大约60kDa。
Apo39
参见实施例1，Apo39(SEQ ID NO83)是D9scFV抗体、KLIP8和Apo AI间之融合蛋白。使用菜豆蛋白启动子和终止子，供构建体的种子特异性表达，并使用PRS信号肽，供融合蛋白对分泌通路之导向表达，又使用KLIP8为可裂解的接头。蛋白质印迹分析(图31B图)使用多克隆Apo AI抗体，在受测试的全部12克隆中，于全种子提取物内检测D9 scFV-KLIP8-Apo AI融合蛋白，分子量大约55kDa。
Apo40参见实施例1，Apo40(SEQ ID NO87)是D9 scFV抗体和ApoAI原间之融合蛋白，有klip8裂解序列将二成份分开。使用菜豆蛋白启动子和终止子，供构建体之种子特异性表达，并使用PRS信号肽，供融合蛋白对分泌通路的导向表达。蛋白质印迹分析(图32(A))使用多克隆Apo AI抗体，在受测试的13之12克隆中，于全种子提取物内检测D9 scFV-klip8-Apo AI原融合蛋白，分子量大约63kDa。
Apo41参见实施例1，Apo41(SEQ ID NO89)是D9 scFV抗体和ApoAI(+met)间之融合蛋白，有klip8裂解序列将二成份分开。使用菜豆蛋白启动子和终止子，供构建体之种子特异性表达，并使用PRS信号肽，供融合蛋白对分泌通路的导向表达。蛋白质印迹分析(图32(B))使用多克隆Apo AI抗体，在受测试的9之8克隆中，于全种子提取物内检测D9 scFV-klip8-Apo AI(+met)融合蛋白，分子量大约63kDa。
Apo42参见实施例1，Apo42(SEQ ID NO91)是D9 scFV抗体和ApoAI原(+met)间之融合蛋白，有klip8裂解序列将二成份分开。使用菜豆蛋白启动子和终止子，供构建体之种子特异性表达，并使用PRS信号肽，供融合蛋白对分泌通路的导向表达。蛋白质印迹分析(图33(A))使用多克隆Apo AI抗体，在受测试的全部13克隆中，于全种子提取物内检测D9 scFV-klip8-Apo AI原(+met)融合蛋白，分子量大约64kDa。
Apo44参见实施例1，Apo44(SEQ ID NO95)是D9 scFV抗体和ApoAI原间之融合蛋白。使用菜豆蛋白启动子和终止子，供构建体之种子特异性表达，并使用PRS信号肽，供融合蛋白对分泌通路的导向表达，又使用KDEL保留信号，把多肽保留在ER内。蛋白质印迹分析(图34(A))使用多克隆Apo AI抗体，在受测试的15之4克隆中，于全种子提取物内检测D9 scFV-Apo AI原-KDEL融合蛋白，分子量大约64kDa。
Apo45参见实施例1，Apo45(SEQ ID NO97)是D9 scFV抗体和ApoAI(+met)间之融合蛋白。使用菜豆蛋白启动子和终止子，供构建体之种子特异性表达，并使用PRS信号肽，供融合蛋白对分泌通路之导向表达，又使用KDEL保留信号，把多肽保留在ER内。蛋白质印迹分析(图34(B))使用多克隆Apo AI抗体，在受测试的全部12克隆中，于全种子提取物内检测D9 scFV-Apo AI(+met)-KDEL融合蛋白，分子量大约63kDa。
Apo46参见实施例1，Apo46(SEQ ID NO99)是D9 scFV抗体和ApoAI原(+met)间之融合蛋白。使用菜豆蛋白启动子和终止子，供构建体之种子特异性表达，并使用PRS信号肽，供融合蛋白对分泌通路之导向表达，又使用KDEL保留信号，把多肽保留在ER内。蛋白质印迹分析(图35(A))使用多克隆Apo AI抗体，在受测试的11之10克隆中，于全种子提取物内检测D9 scFV-Apo AI原(+met)-KDEL融合蛋白，分子量大约64kDa。
实施例4
载脂蛋白定位之蛋白质印迹分析按上述进行油体分离(van Rooijen & Moloney，1995)，改变如下。简言之，取250毫克干成熟种子，表面以70％乙醇杀菌，用无菌水淋洗二次，磷酸盐缓冲液一次(100mM磷酸盐缓冲液pH 8，和0.5MNaCl)。洗后，种子再悬浮于磷酸盐缓冲液内供分析之用，再用杀菌研钵和杵槌磨。磨后，样品移到离心瓶内，在RT以10,000g离心15分钟。离心后，从水相(AQ)除去含油体的脂肪垫，移至1.5mL微离心管。油体再悬浮于严格度低的磷酸盐缓冲液(100mM磷酸盐缓冲液pH8，和0.5M NaCl)。样品在4℃，以10,000g离心15分钟，除去下层液。测试下层液(PW)和磷酸盐洗过的油体(PO)内载脂蛋白之存在。油体随即再悬浮于高严格性的尿素缓冲液内(8M尿素在100mM碳酸钠缓冲液内，pH 8)。样品在4℃，于10,000g离心15分钟，除去下层液。下层液(UW)和尿素洗过的油体(UO)，测试载脂蛋白之存在。须知油体经低、高严格度洗液处理，以除去与油体结合之蛋白质，油质蛋白抵抗高严格度洗液，与油体级份保留。取250mg干种子在4mL微粒体研磨缓冲液内(0.5M蔗糖，0.2M Hepes-NaOH缓冲液，pH7.4)，用研钵和杵槌磨成浆液，得微粒体级份(ER)。浆液在4℃，以10,000g离心30分钟。把上层液移至新管内，于4℃，以10,000g离心2小时，用吊桶式离心转子进行超离心。沉淀用微粒体研磨缓冲液洗涤，以10,000g快速离心5分钟，再悬浮于10-15μL微粒体研磨缓冲液内，在-20℃储存。
未导向构建体参见图36A图，(Apo11)原Apo AI-和成熟(Apo10)Apo AI-GFP融合体，无额外导向信号，在不同级份检验。Apo10显示虽然在所有细胞级份均检测到成熟Apo AI-GFP融合蛋白，但呈现更多蛋白累积在用磷酸盐缓冲液和尿素洗液级份洗过的油体。此表示虽然Apo10不拥有对油体的亲和性，但高严格度洗液即足以从油体表面加以除去。Apo11表示Apo AI天然原序列存在，把Apo AI-GFP融合蛋白导向油体级份，其程度较失去肽原者更大，而即使用到高严格度洗液，蛋白仍结合于油体。呈现Apo AI肽原有“固着”序列的作用，把Apo AI原保留在油体表面。在此等级份可检测得多种低分子量带，可以降解产物。
导向油体之构建体Apo AI-GFP融合蛋白与油体紧密相关之型态，亦可见于油体导向之构建体(图36B图)。(Apo13)原和成熟(Apo12)Apo AI-GFP融合，是框内融合于油质蛋白之羧基末端，用做对油体之导向信号。参见前述未导向Apo AI原-GFP融合，蛋白主要与磷酸盐和尿素洗过油体级份结合。在此等级份亦可检测得多种较低分子量带，表示与油体结合的级份有些独特，以致累积可能降解的产物。
导向分泌系统之构建体添加把蛋白导向分泌通路的PRS信号肽(Sijmons等人，1990，Bio/technology，8217-221)，作为原(Apo16)和成熟(Apo15)型之Apo AI-GFP(图37)的框内翻译融合体。通常，这会造成融合蛋白分泌于植物细胞的细胞外间隙(质外体)。然而，检验二构建体的细胞级份时，在所有级份都可检测到Apo AI-GFP融合蛋白，而在油体级份检测到更多蛋白。检验Ponceau-S染色的免疫印迹时(图37上半)，在油体级份内亦观察到重组融合蛋白大小的带状。Apo AI天然原序列存在，并不表示与特殊细胞级份结合的分泌融合蛋白有所改变。植物前序列辨识信号(PRS)肽呈现对Apo AI肽原的“固着”特性发生干扰。
Apo AI-GFP在叶部的组成型表达检验组成型表达未导向和分泌原型和成熟型Apo AI-GFP之叶组织，以测定Apo AI-GFP融合蛋白是否可累积于不生成油的组织。叶组织从转基因植物匀浆化(如实施例2所述)，组成型表达未导向的原(Apo18)和成熟(Apo17)型Apo AI-GFP，以及分泌型的原(Apo20)和成熟(Apo19)型Apo AI-GFP，用于免疫印迹法。另从野生型(c24)植物取又叶材料，作为阴性对照，并从UR2(遍在蛋白驱动的油质蛋白-GFP)植物和UG-14(遍在蛋白驱动之GFP)植物，供叶表达之阳性对照。利用SDS-PAGE分成相似量的蛋白，利用免疫印迹法，以抗GFP抗体检测Apo AI-GFP融合蛋白(图38下半)。
在非转化株检测到微弱带，而利用抗GFP抗体，可在免疫印迹上轻易检测到遍在蛋白驱动的GFP(UG-14)和油质蛋白-GFP(UR2)二者融合。然而，虽然利用膜的Ponceau-S染色，可见到免疫印迹上载录相似量的叶蛋白(图38上半)，但任何Apo AI-GFP融合蛋白构建体均未检测到带状。在免疫印迹的背景检测到的微弱带，可能因与Rubisco交叉反应性之故，Rubisco是叶组织中所见最主要蛋白(RJ Spreitzer和ME Salvucci(2002)《Rubisco更佳酶之结构，调节性互动及可能性》，Annu Rev.Plant Biol 53449-475)，按照分子量标志，在免疫印迹的Ponceau-S染色图上，利用大小即可看出。
种子内未导向而分泌的Apo AI之种子特异性表达从全种子提取物内显示有些累积无论是原型或成熟Apo AI蛋白的T2世带Apo AI转基因植物，各选取一转基因株。在推定转基因的植物株当中，只有下述一株显示任何蛋白表达Apo21(未导向成熟ApoAI)、Apo22(未导向Apo AI原)和Apo29(分泌之成熟Apo AI)；对Apo30(分泌Apo AI原)发现二株。含有构建体Apo23和Apo24的所有转基因植物株，显示表达和累积油质蛋白-Apo AI融合蛋白。利用SDS-PAGE分成类似量的蛋白，并利用免疫印迹法，以抗Apo AI抗体检测Apo AI蛋白(图39)。从非转化植物(c24)制备相似蛋白提取物，包含供免疫印迹用的阴性对照。只有在Apo22-3株(未导向Apo AI原)，观察到单独供Apo AI表达的带状正确大小(预定分子量对成熟Apo AI为28.3kDa，对Apo AI原为29.3kDa)。在Apo21-11(未导向成熟Apo AI)内检测到的主要带，是不正确大小，虽然在Apo29-11(分泌之成熟Apo AI)和Apo30-14(分泌之Apo AI原)检测到只有微小带，却无一为正确大小。然而，对于油质蛋白融合Apo23-11(油质蛋白—成熟Apo AI)和Apo24-6(油质蛋白-Apo AI原)二者而言，利用抗Apo AI抗体检测到显著量的Apo AI融合蛋白，其亦可在Ponceau-S染色的免疫印迹(上半图)内检测到。
未导向Apo AI(Apo22)T3种子之亚细胞定位未导向Apo AI蛋白原型(Apo22)的种子特异性表达，及其与特异性细胞级份之结合，是在成熟种子内检测到的(图40)。种子按上述匀浆化和处理，而细胞级份经免疫印迹法，以抗体对Apo AI。Apo22-3显示Apo AI原天然序列的存在，把Apo AI蛋白导向油体级份，而蛋白需要高严格度洗液，从油体除去蛋白。有些蛋白亦可在水相内检测，表示并非全部Apo AI原蛋白均与油体结合。在此等级份可检测到多种较低分子量带，可能为降解产物。
实施例5载脂蛋白定位用之共聚焦显微术使用钳子和解剖显微镜，在培氏皿内的无菌水下，从Apo AI-GFP长角果解剖不成熟胚。用显微镜玻片盖轻压不成熟种子，从种子外皮除去胚。胚用吸量管移到1.5mL微离心管内，加水到最后容量为1mL。在最后浓度1μg/μL使用尼罗红(分子探针)。在稀释尼罗红内之胚，于室温黑暗中保温15分钟。胚在无菌水中淋洗三次，在水中装在玻片上供显微检查。用外科小刀单纯切下少级份叶(0.5cm2)，于水中用滑盖装在显微镜玻片上，制备叶表皮细胞。放置叶区段，使下面表皮朝上(较不会干扰自身萤光叶绿体)。
由拟南芥胚分析所有GFP依赖性萤光，把叶表皮细胞在水中装好，供显微观察，并用Zeiss LSM 510雷射扫描共聚焦显微镜(Edmonton，AB)加以检验。为同时检测GFP和尼罗红，使用线依序单一追踪模式，以488nm和543nm光的AOTF控制激发，分别设定在20％和100％。使用Plan-Appochromat 63x/1.4Oil DIC物镜，有5X扫描变焦。针孔调到最佳，对波道2(绿色)在94μm，而波道1(红色)在106μm。
所得显微照片见图42至45。未导向Apo AI原-GFP融合(Apo11)和尼罗红染色油体间之共同定位(以黄色表示)，可见图41(D-F)图。在Apo12(即使用油质蛋白导向油体的GFP所融合成熟Apo，见图41之G-I)和Apo13(即使用油质蛋白导向油体的GFP所融合Apo AI原，见图42之A-C)间，亦可共同定位(用黄色表示)。未导向Apo AI原-GFP融合(Apo18)和尼罗红染色油体间之共同定位(用黄色表示)明显(图43之D-F)。Apo AI-GFP融合蛋白(Apo19)和油体间，未见共同定位(图43G-H)。在图44中，叶内未显示共同定位。总之，在无油体导向(即油质蛋白)情况下，只在胚内(于中性脂质存在下)而且只在细胞质内表达Apo AI原肽时，观察到Apo AI共同定位(即分泌时则否)。
实施例6表达拟南芥种子的Apo25，26，28之裂解和HPLC分析Apo25，Apo26和Apo28重组蛋白之裂解按照前述进行油体之分离(van Rooijen & Moloney，1995)，有下列改变。简言之，取250mg干成熟种子，表面用70％乙醇杀菌，用无菌水淋洗二次，磷酸盐缓冲液一次(100mM磷酸盐缓冲液pH 8，有0.5M NaCl)。洗后，种子再悬浮于磷酸盐缓冲液内，供分析之用，再用杀菌过的研钵和杵槌磨。磨后，样品移到离心瓶，在RT以10,000g离心15分钟。离心后，含油体的脂肪垫移到1.5mL微离心管，再悬浮于尿素缓冲液内(8M尿素在100mM碳酸钠内，pH 8)。样品在4℃，以10,000g离心15分钟，把下层液除去。脂肪垫再悬浮于无菌ddHO内，在4℃以10,000g离心15分钟，除去下层液。油体再悬浮于15μL无菌ddH2O内，在4℃黑暗中储存。于含100mM磷酸盐缓冲液pH 4.5的20μL反应容量内，在37℃进行裂解反应2小时，最后的蛋白酶对油体蛋白比为1∶100。样品反应如下将20μg纯化Apo25，Apo26或Apo28，组合2μL 1M磷酸盐缓冲液pH 4.5(最后浓度100mM)、2μL凝乳酶(0.1μg/μl)，以无菌ddH2O调至最后容量20μL。2小时后，裂解反应经离心15分钟，从脂肪垫除去下层液，各相分析重组蛋白质。
Apo25，Apo26和Apo28利用反相层析法纯化大约取1000μg的Apo25，Apo26或Apo28，利用凝乳酶在37℃裂解2小时。俟裂解反应完成后，反应在4℃，以10,000g离心15分钟，回收下层液。脂肪垫再悬于尿素缓冲液(8M尿素在0.1mM碳酸钠缓冲液内，pH 8)，离心15分钟。回收下层液或洗液，又重复洗净三次，每次回收下层液，汇集于15mL Falcon管内。在尿素洗涤完成后，洗液全份放入1.5mL微离心管内，离心15分钟，除去任何污染的油体残基。回收下层液，使用0.2微米过滤器过滤入新的15mL Falcon管内。VYDAC 214TP54C4氧化硅5微米(Grace Vydac，Anaheim，CA)反相层析管柱(0.24×25cm)，在缓冲液A(10％乙腈和0.1％三氟乙酸)内，以2mL/min的流量加以平衡。汇集的凝乳酶所裂解Apo25，Apo26或Apo28尿素下层液，装载于管柱上。对管柱施以0至60％缓冲液B(95％乙腈，0.1％三氟乙酸)的线型梯度，洗提Apo AI，使用Apo AI(US Biological，型号A2299-10)作为标准，以供比较来自Apo25，Apo26和Apo28的裂解产物。收集19.6’至20.8’(每0.2’＝0.4mL)。比较在214，254，280和326nm的DAD微量之相对强度，表示在19.5-21.0’区域内洗提物料，最能代表Apo AI多肽(图45A图)。与先前注射0.020mL的相同样品相较，强度峰值亦提高。为了纯化Apo25(油质蛋白-klip8-Apo AI(met+))之裂解产物，从7至25’各收集凝乳酶处理级份@1mL。主要多肽峰值在20.5’(图45B图)，刚好比所拟hApo AI标准稍后0.2’。为了纯化Apo26(油质蛋白-klip8-Apo AI原(met+))之裂解产物，收集7至25’之级份各1mL。主要多肽峰值在18’(图45C图)，比所拟hApo AI标准早2.4’。为纯化Apo28(油质蛋白-klip8-Apo AI原)之裂解产物，收集7至25’之级份各1mL。主要多肽峰值在18’(图45D图)，比所拟hApo AI标准早2.4’，但与Apo26运转相似。
质谱测定法质谱系Doug Olson(加拿大国家研究委员会植物生物科技学院生物分析光谱测定组，Saskatoon，SK)对飞翔(MALDI-TOF)质谱仪器(美国加州佛斯特市应用生物系统公司)的应用生物系统航行者-DE STR基质协助雷射解吸附电离时间的要求。样品是使用在30％乙腈/70％水/0.1％TFA内饱和的芥子酸(sinapinic acid)基质，点样在OPI-TOF LCMALDI插段(加州佛斯特市应用生物系统公司)上。离子以+20kV加速，质量以线型模式检测，使用马心肌红蛋白，作为外部校准符。纯化重组成熟Apo25蛋白的电喷电离质谱测定法，得分子质量28,325Da，比所计算分子量28,319Da多6Da。观察值与预期值间之差异，可能因样品有限，导致信噪比下降，和准确性降低。成熟Apo AI的预期分子量为28,187Da，但因额外Met残基存在，裂解之重组成熟Apo AI蛋白的分子量增加。纯化的标准hApo AI蛋白亦利用质谱测定法分析，在25,969Da和22,815Da拥有二分明峰值。此二观察值均比预期值28,187Da大降；然而，此二主要的较低分子量在先前的免疫印迹中已经观察到。此项分子量降低容易造成人体和重组蛋白的洗提型态稍有不同，如RP-HPIC所见。
实施例7红花的转化此项转化方案与T.K.Orlilcowska等人((1995)Plant Cell，Tissueand Organ Culture 4085-91)方案相似，但对于把S-317转化和使用草铵膦作为选择性标志两方面，有所修饰和改进。把无损、无破或无病的S-317加州红花变体的种子，在0.1％HCl2内去杂质12分钟，接着用杀菌水淋洗4-5次。杀菌种子在1％蔗糖和0.25％Gelrite之MS培养基(T.Murashige T.和F Skoog F(1962)Physiol.Plant.15473-497)上，于黑暗中发芽。从冷冻甘油存料，在具有抗生素选择的5毫升AB最少液体培养基内，开始土壤杆菌培养物，在28℃成长48小时。此培养物整份在具有供转化选择的5ml Luria液体培养基内成长过夜。6-8ml的细菌细胞用AB培养基洗二次，补充到最后细胞密度0.4-0.5(0D600)。
从发芽的幼苗除去生长两天的子叶，浸在制备的土壤杆菌细胞内，平板接中在3％蔗糖、4μM N6-苄基腺嘌呤(BA)和0.8μM萘乙酸(NAA)之MS培养基上。板在黑暗状态下保温于21℃。三天后，移到具有300mg/L timentin的同样培养基。三天后，把外植体放到添加0.5mg/L草铵膦的选择性培养基上。让芽继续抽长，每周把外植体移到无植物激素的MS培养基上，但为KNO3基础量的两倍。把从起始外植体抽长到超过10mm的芽切除，在选择上个别成长。为供生根，把代表推定转基因组织的绿芽放在具有2％蔗糖、10μM吲哚丁酸和0.5μM NAA的MS培养基上。把生根的芽移到排水良好的少土壤混合料，在高湿度和12小时光照下成长。
实施例8此项转化程序类似J.Dong和A.McHughen(Plant Cell Reports(1991)10555-560)、J.Dong和A.McHughen(Plant Sciences(1993)8861-71)以及Mlynarova等人(Plant Cell Reports(1994)13282-285)的方案。把无损、无破或无病的亚麻种子，在70％乙醇溶液内去杂质5-7分钟，接着在50％漂白液内用Tween 20(每100ml 3-4滴)处理25分钟，继续搅拌。种子以杀菌蒸馏水淋洗5-7次。去杂质的种子放在洋红瓮内，在具有2％蔗糖和0.3％Gelrite_的MS培养基(T.Murashige和F Skoog(1962)Physiol.Plant.15473-497)，于光照下发芽。为了转化，让土壤杆菌培养物在AB液体培养基内成长过夜，加适当抗生素供选择。把6-8ml过夜细胞洗二次，再悬浮于5ml AB液体培养基内；把此料2ml加到98ml诱导培养基(MS基础培养基)，具有3％蔗糖、5μM 6-苄氨基嘌呤(BA)和0.25μM α-萘乙酸(NAA)，调节至最后0D600为1.0。
截取胚轴外植体，在制备的土壤杆菌细胞溶液内接种约4小时(在此时间轻轻搅动板1-2次)。感染期后，从液体接种培养基除去外植体，转印在无菌滤纸上。把15-20外植体平板接种在组织培养板内的0.7％琼脂凝固诱导培养基上。用塑料包装纸把板密封，在光照状态(23-24℃)下，把外植体共同培养48小时。二天后，把鲜绿分生组织的外植体移到含300ml/L Timentin(预选培养基)的同样培养基，用塑料包装纸包装。三天后，把培养物移到含10mg/L DL PPT的上述培养基(选择1)。板用Parafilm_包装，在光照状态下，保温于24℃。每二星期移动培养基，保持在此培养基上一个月。为供芽抽长，每二星期把培养物移到洋红瓮内的选择培养基II上(MS基础培养基，含2％蔗糖，500mg/L MES缓冲液，300mg/L Timentin和10mg/L DL PPT)。经选择后存活的推定转化芽，为深绿色，分别种植于选择II培养基上，经7-10天形成强劲的根。把生根的芽移到小盆内的杀菌温室土壤混合物，幼苗用清洁塑料杯覆盖，使适应水土。为使成熟，把活泼成长的植物移到1加仑盆，有排水良好的土壤混合物，并在温室条件下成长。
虽然本发明已参见目前认为优选的实施方式加以说明，惟须知本发明不限于所揭示的实施方式。反之，本发明旨在涵盖所附权利要求书之精神和范围内包含之各种修饰和等效方式。
所有出版物、专利和专利申请在此均全文列入参考，这与将各出版物、专利或专利申请均具体地和个别地全文列入参考一样。
序列摘要SEQ ID NO1和2分别给出人体Apo AI原蛋白的核苷酸序列和推定的氨基酸序列。
SEQ ID NO3和4分别给出人体Apo AI Milano蛋白的核苷酸序列和推定的氨基酸序列。
SEQ ID NO5和6分别给出人体Apo AI Paris蛋白的核苷酸序列和推定的氨基酸序列。
SEQ ID NO7和8是表1中所列已知人体载脂蛋白序列。
SEQ ID NO9-24是表1中所列已知载脂蛋白A-I序列。
SEQ ID NO25-34是表1中所列已知载脂蛋白A-IV序列。
SEQ ID NO35-54是表1中所列已知载脂蛋白E序列。
SEQ ID NO56给出拟南芥(Arabidopsis thaliana)硫氧还蛋白之核酸序列。
SEQ ID NO57给出可溶性绿色荧光蛋白之核酸序列。
SEQ ID NO58给出PRS信号序列之氨基酸序列。
SEQ ID NO59-116是表3中所列已知油质蛋白油体蛋白序列。
SEQ ID NO117-129是表3中所列已知caleosin油体蛋白序列。
SEQ ID NO130-137是表3中所列已知steroleosin油体蛋白序列。
SEQ ID NO138给出已知拟南芥油质蛋白油体蛋白序列。
SEQ ID NO139给出已知油菜油质蛋白油体蛋白序列。
SEQ ID NO140给出已知拟南芥caleosin油体蛋白核酸序列。
SEQ ID NO141给出已知拟南芥caleosin油体蛋白核酸序列。
SEQ ID NO142给出已知steroleosin油体蛋白核酸序列。
SEQ ID NO143给出klip8裂解序列用之核苷酸序列。
SEQ ID NO144和145分别给出Apo10克隆的核苷酸序列和推定的氨基酸序列。
SEQ ID NO146给出正向引物1186之核苷酸序列，与GFP的5’区互补，并设计来除去NcoI位点。
SEQ ID NO147给出反向引物1187之核苷酸序列，与GFP的3’区互补，其设计是在终止密码子后，加PstI、XhoI和HindIII位点。
SEQ ID NO148给出正向引物1190之核苷酸序列，与成熟Apo AI的5’区互补，其设计是在基因起始处加NcoI位点。
SEQ ID NO149给出反向引物1189之核苷酸序列，与成熟Apo AI的5’区互补，其设计是在除去基因的终止密码子，并加BamHI位点，以助产生与GFP之框内翻译融合体。
SEQ ID NO150和151分别给出Apo11克隆的核苷酸和推定的氨基酸序列。
SEQ ID NO152给出正向引物1191之核苷酸序列，与Apo AI原之5’区互补，其设计在于基因起始处加NcoI位点。
SEQ ID NO153和154分别给出Apo12克隆的核苷酸和推定的氨基酸序列。
SEQ ID NO155和156分别给出Apo13克隆的核苷酸和推定的氨基酸序列。
SEQ ID NO157和158分别给出Apo15克隆的核苷酸和推定的氨基酸序列。
SEQ ID NO159和160分别给出Apo16克隆的核苷酸和推定的氨基酸序列。
SEQ ID NO161和162分别给出Apo17克隆的核苷酸和推定的氨基酸序列。
SEQ ID NO163和164分别给出Apo18克隆的核苷酸和推定的氨基酸序列。
SEQ ID NO165和166分别给出Apo19克隆的核苷酸和推定的氨基酸序列。
SEQ ID NO167给出正向引物1177之核苷酸序列，与PRS/Apo AI(克隆Apo15)的5’区互补，其设计在于把在起始密码子含有BspHI位点的植物预序列(PRS)开始加以扩增。
SEQ ID NO168给出反向引物1178之核苷酸序列，与Apo AI的3’区互补，其设计在于除去基因的终止密码子，并加BamHI位点，以助产生与GFP框内翻译融合体。
SEQ ID NO169和170分别给出Apo20克隆的核苷酸和推定的氨基酸序列。
SEQ ID NO171和172分别给出Apo21克隆的核苷酸和推定的氨基酸序列。
SEQ ID NO173给出正向引物1203的核苷酸序列，与Apo AI的5’区互补，其设计在于成熟Apo AI开始时加NcoI位点。
SEQ ID NO174给出反向引物1206的核苷酸序列，与Apo AI的3’区互补，其设计在于终止密码子后加HindIII位点。
SEQ ID NO175和176分别给出Apo22克隆的核苷酸和推定的氨基酸序列。
SEQ ID NO177给出正向引物1201的核苷酸序列，与Apo AI原的5’区互补，其设计是在Apo AI原开始加NcoI位点。
SEQ ID NO178和179分别给出Apo23克隆的核苷酸和推定的氨基酸序列。
SEQ ID NO180和181分别给出Apo24克隆的核苷酸和推定的氨基酸序列。
SEQ ID NO182和183分别给出Apo25克隆的核苷酸和推定的氨基酸序列。
SEQ ID NO184和185分别给出Apo26克隆的核苷酸和推定的氨基酸序列。
SEQ ID NO186和187分别给出Apo27克隆的核苷酸和推定的氨基酸序列。
SEQ ID NO188给出正向引物1200的核苷酸序列，与成熟Apo AI的5’区互补，其设计是在Apo AI原开始时加XhoI位点，和额外核苷酸以方便框内克隆于klip8裂解序列内。
SEQ ID NO189和190分别给出Apo 27M克隆的核苷酸和推定的氨基酸序列。
SEQ ID NO191给出正向引物1202的核苷酸序列，与人体Apo AI的5’区互补，其设计在将人体Apo AI序列扩增，于mat-Apo AI开始加XhoI位点，和额外核苷酸，以方便框内克隆于klip8裂解序列内。
SEQ ID NO192给出正向引物1225之核苷酸序列是平端引物，使碱基对从C突变至T，把Arg残基改变为Cys残基，因而产生Apo-Milano突变。
SEQ ID NO193和194分别给出Apo28克隆之核苷酸和推定的氨基酸序列。
SEQ ID NO195给出正向引物1205的核苷酸序列，与Apo AII原的5’区互补，设计成平端引物，加沉默突变，以除去第一XhoI位点。
SEQ ID NO196和197分别给出Apo29克隆的核苷酸和推定的氨基酸序列。
SEQ ID NO198和199分别给出Apo30克隆的核苷酸和推定的氨基酸序列。
SEQ ID NO200和201分别给出Apo31克隆的核苷酸和推定的氨基酸序列。
SEQ ID NO202和203分别给出Apo32克隆的核苷酸和推定的氨基酸序列。
SEQ ID NO240和205分别给出Apo33克隆的核苷酸和推定的氨基酸序列。
SEQ ID NO206和207分别给出Apo34克隆的核苷酸和推定的氨基酸序列。
SEQ ID NO208和209分别给出Apo35克隆的核苷酸和推定的氨基酸序列。
SEQ ID NO210给出反向引物1208的核苷酸序列，与Apo AI原的3’区互补，其设计是在终止密码子之前加KDEL序列，并在终止密码子之后加HindIII位点。
SEQ ID NO211和212分别给出Apo36克隆的核苷酸和推定的氨基酸序列。
SEQ ID NO213和214分别给出Apo37克隆的核苷酸和推定的氨基酸序列。
SEQ ID NO215和216分别给出Apo38克隆的核苷酸和推定的氨基酸序列。
SEQ ID NO217和218分别给出Apo39克隆的核苷酸和推定的氨基酸序列。
SEQ ID NO219给出正向引物1207之核苷酸序列，与klip8裂解序列之5’区互补，其设计在将klip8序列开始扩增，并在起始密码子加SalI位点。
SEQ ID NO220和221分别给出Apo40克隆的核苷酸和推定的氨基酸序列。
SEQ ID NO222和223分别给出Apo41克隆的核苷酸和推定的氨基酸序列。
SEQ ID NO224和225分别给出Apo42克隆的核苷酸和推定的氨基酸序列。
SEQ ID NO226和227分别给出Apo43克隆的核苷酸和推定的氨基酸序列。
SEQ ID NO228和229分别给出Apo44克隆的核苷酸和推定的氨基酸序列。
SEQ ID NO230和231分别给出Apo45克隆的核苷酸和推定的氨基酸序列。
SEQ ID NO232和233分别给出Apo46克隆的核苷酸和推定的氨基酸序列。
SEQ ID NO234和235分别给出Apo47克隆的核苷酸和推定的氨基酸序列。
SEQ ID NO236给出正向引物1226的核苷酸序列，与玉米油酸蛋白序列的5’区互补，其设计在于把玉米油酸蛋白序列扩增，并在起始密码子加NcoI位点。
SEQ ID NO237给出正向引物1227的核苷酸序列，与玉米油酸蛋白序列的3’区互补，其设计在于把玉米油酸蛋白扩增，除去基因的终止密码子，并加HindIII，以助产生与klip8/mat Apo AI的框内翻译融合体。
SEQ ID NO238给出正向引物1228的核苷酸序列，与Apo25克隆的5’区互补，其设计在于把Apo25序列扩增，并于起始密码子加SalI位点。
SEQ ID NO239给出反向引物1229的核苷酸序列，与Apo25克隆的3’区互补，其设计在于把Apo25序列扩增，并于终止密码子之后加BamHI位点。
SEQ ID NO240给出单链油体D9scFv的氨基酸序列。
表1已知载脂蛋白序列的实例



表2已知载脂蛋白突变和修饰的实例



表3已知油体蛋白序列的实例




序列表<110>赛姆生物系统遗传公司<120>在转基因植物中产生载脂蛋白的方法<130>9369-310<140>
<141>
<150>US 60/519,606<151>2003-11-14<150>US 60/579,733<151>2004-06-16<160>251<170>PatentIn version 3.3<210>1<211>804<212>DNA<213>Homo sapiens<400>1atgaaagctg cggtgctgac cttggccgtg ctcttcctga cggggagcca ggctcggcat60ttctggcagc aagatgaacc cccccagagc ccctgggatc gagtgaagga cctggccact120gtgtacgtgg atgtgctcaa agacagcggc agagactatg tgtcccagtt tgaaggctcc180gccttgggaa aacagctaaa cctaaagctc cttgacaact gggacagcgt gacctccacc240ttcagcaagc tgcgcgaaca gctcggccct gtgacccagg agttctggga taacctggaa300aaggagacag agggcctgag gcaggagatg agcaaggatc tggaggaggt gaaggccaag360gtgcagccct acctggacga cttccagaag aagtggcagg aggagatgga gctctaccgc420cagaaggtgg agccgctgcg cgcagagctc caagagggcg cgcgccagaa gctgcacgag480ctgcaagaga agctgagccc actgggcgag gagatgcgcg accgcgcgcg cgcccatgtg540gacgcgctgc gcacgcatct ggccccctac agcgacgagc tgcgccagcg cttggccgcg600cgccttgagg ctctcaagga gaacggcggc gccagactgg ccgagtacca cgccaaggcc660accgagcatc tgagcacgct cagcgagaag gccaagcccg cgctcgagga cctccgccaa720ggcctgctgc ccgtgctgga gagcttcaag gtcagcttcc tgagcgctct cgaggagtac780actaagaagc tcaacaccca gtga 804<210>2
<211>267<212>PRT<213>Homo sapiens<400>2Met Lys Ala Ala Val Leu Thr Leu Ala Val Leu Phe Leu Thr Gly Ser1 5 10 15Gln Ala Arg His Phe Trp Gln Gln Asp Glu Pro Pro Gln Ser Pro Trp20 25 30Asp Arg Val Lys Asp Leu Ala Thr Val Tyr Val Asp Val Leu Lys Asp35 40 45Ser Gly Arg Asp Tyr Val Ser Gln Phe Glu Gly Ser Ala Leu Gly Lys50 55 60Gln Leu Asn Leu Lys Leu Leu Asp Asn Trp Asp Ser Val Thr Ser Thr65 70 75 80Phe Ser Lys Leu Arg Glu Gln Leu Gly Pro Val Thr Gln Glu Phe Trp85 90 95Asp Asn Leu Glu Lys Glu Thr Glu Gly Leu Arg Gln Glu Met Ser Lys100 105 110Asp Leu Glu Glu Val Lys Ala Lys Val Gln Pro Tyr Leu Asp Asp Phe115 120 125Gln Lys Lys Trp Gln Glu Glu Met Glu Leu Tyr Arg Gln Lys Val Glu130 135 140Pro Leu Arg Ala Glu Leu Gln Glu Gly Ala Arg Gln Lys Leu His Glu145 150 155 160Leu Gln Glu Lys Leu Ser Pro Leu Gly Glu Glu Met Arg Asp Arg Ala165 170 175Arg Ala His Val Asp Ala Leu Arg Thr His Leu Ala Pro Tyr Ser Asp180 185 190Glu Leu Arg Gln Arg Leu Ala Ala Arg Leu Glu Ala Leu Lys Glu Asn195 200 205Gly Gly Ala Arg Leu Ala Glu Tyr His Ala Lys Ala Thr Glu His Leu
210 215 220Ser Thr Leu Ser Glu Lys Ala Lys Pro Ala Leu Glu Asp Leu Arg Gln225 230 235 240Gly Leu Leu Pro Val Leu Glu Ser Phe Lys Val Ser Phe Leu Ser Ala245 250 255Leu Glu Glu Tyr Thr Lys Lys Leu Asn Thr Gln260 265<210>3<211>731<212>DNA<213>Homo sapiens<400>3gatgaacccc cccagagccc ctgggatcga gtgaaggacc tggccactgt gtacgtggat60gtgctcaaag acagcggcag agactatgtg tcccagtttg aaggctccgc cttgggaaaa120cagctaaacc taaagctcct tgacaactgg gacagcgtga cctccacctt cagcaagctg180cgcgaacagc tcggccctgt gacccaggag ttctgggata acctggaaaa ggagacagag240ggcctgaggc aggagatgag caaggatctg gaggaggtga aggccaaggt gcagccctac300ctggacgact tccagaagaa gtggcaggag gagatggagc tctaccgcca gaaggtggag360ccgctgcgcg cagagctcca agagggcgcg cgccagaagc tgcacgagct gcaagagaag420ctgagcccac tgggcgagga gatgcgcgac gcgcgcgcgc ccatgtggac gcgctgcgca480cgcatctggc cccctacagc gacgagctgc gccagtgctt ggccgcgcgc cttgaggctc540tcaaggagaa cggcggcgcc agactggccg agtaccacgc caaggccacc gagcatctga600gcacgctcag cgagaaggcc aagcccgcgc tcgaggacct ccgccaaggc ctgctgcccg660tgctggagag cttcaaggtc agcttcctga gcgctctcga ggagtacact aagaagctca720acacccagtg a 731<210>4<211>243<212>PRT<213>Homo sapiens<400>4Asp Glu Pro Pro Gln Ser Pro Trp Asp Arg Val Lys Asp Leu Ala Thr1 5 10 15
Val Tyr Val Asp Val Leu Lys Asp Ser Gly Arg Asp Tyr Val Ser Gln20 25 30Phe Glu Gly Ser Ala Leu Gly Lys Gln Leu Asn Leu Lys Leu Leu Asp35 40 45Asn Trp Asp Ser Val Thr Ser Thr Phe Ser Lys Leu Arg Glu Gln Leu50 55 60Gly Pro Val Thr Gln Glu Phe Trp Asp Asn Leu Glu Lys Glu Thr Glu65 70 75 80Gly Leu Arg Gln Glu Met Ser Lys Asp Leu Glu Glu Val Lys Ala Lys85 90 95Val Gln Pro Tyr Leu Asp Asp Phe Gln Lys Lys Trp Gln Glu Glu Met100 105 110Glu Leu Tyr Arg Gln Lys Val Glu Pro Leu Arg Ala Glu Leu Gln Glu115 120 125Gly Ala Arg Gln Lys Leu His Glu Leu Gln Glu Lys Leu Ser Pro Leu130 135 140Gly Glu Glu Met Arg Asp Arg Ala Arg Ala His Val Asp Ala Leu Arg145 150 155 160Thr His Leu Ala Pro Tyr Ser Asp Glu Leu Arg Gln Cys Leu Ala Ala165 170 175Arg Leu Glu Ala Leu Lys Glu Asn Gly Gly Ala Arg Leu Ala Glu Tyr180 185 190His Ala Lys Ala Thr Glu His Leu Ser Thr Leu Ser Glu Lys Ala Lys195 200 205Pro Ala Leu Glu Asp Leu Arg Gln Gly Leu Leu Pro Val Leu Glu Ser210 215 220Phe Lys Val Ser Phe Leu Ser Ala Leu Glu Glu Tyr Thr Lys Lys Leu225 230 235 240Asn Thr Gln
<210>5<211>731<212>DNA<213>Homo sapiens<400>5gatgaacccc cccagagccc ctgggatcga gtgaaggacc tggccactgt gtacgtggat60gtgctcaaag acagcggcag agactatgtg tcccagtttg aaggctccgc cttgggaaaa120cagctaaacc taaagctcct tgacaactgg gacagcgtga cctccacctt cagcaagctg180cgcgaacagc tcggccctgt gacccaggag ttctgggata acctggaaaa ggagacagag240ggcctgaggc aggagatgag caaggatctg gaggaggtga aggccaaggt gcagccctac300ctggacgact tccagaagaa gtggcaggag gagatggagc tctaccgcca gaaggtggag360ccgctgcgcg cagagctcca agagggcgcg cgccagaagc tgcacgagct gcaagagaag420ctgagcccac tgggcgagga gatgcgcgac gcgcgcgcgc ccatgtggac gcgctgcgca480cgcatctggc cccctacagc gacgagctgc gccagcgctt ggccgcgcgc cttgaggctc540tcaaggagaa cggcggcgcc agactggccg agtaccacgc caaggccacc gagcatctga600gcacgctcag cgagaaggcc aagcccgcgc tcgaggacct ccgccaaggc ctgctgcccg660tgctggagag cttcaaggtc agcttcctga gcgctctcga ggagtacact aagaagctca720acacccagtg a 731<210>6<211>242<212>PRT<213>Homo sapiens<400>6Asp Glu Pro Pro Gln Ser Pro Trp Asp Arg Val Lys Asp Leu Ala Thr1 5 10 15Val Tyr Val Asp Val Leu Lys Asp Ser Gly Arg Asp Tyr Val Ser Gln20 25 30Phe Glu Gly Ser Ala Leu Gly Lys Gln Leu Asn Leu Lys Leu Leu Asp35 40 45Asn Trp Asp Ser Val Thr Ser Thr Phe Ser Leu Arg Glu Gln Leu Gly50 55 60Pro Val Thr Gln Glu Phe Trp Asp Asn Leu Glu Lys Glu Thr Glu Gly65 70 75 80
Leu Arg Gln Glu Met Ser Lys Asp Leu Glu Glu Val Lys Ala Lys Val85 90 95Gln Pro Tyr Leu Asp Asp Phe Gln Lys Lys Trp Gln Glu Glu Met Glu100 105 110Leu Tyr Arg Gln Lys Val Glu Pro Leu Arg Ala Glu Leu Gln Glu Gly115 120 125Ala Arg Gln Lys Leu His Glu Leu Gln Glu Lys Leu Ser Pro Leu Gly130 135 140Glu Glu Met Arg Asp Cys Ala Arg Ala His Val Asp Ala Leu Arg Thr145 150 155 160His Leu Ala Pro Tyr Ser Asp Glu Leu Arg Gln Arg Leu Ala Ala Arg165 170 175Leu Glu Ala Leu Lys Glu Asn Gly Gly Ala Arg Leu Ala Glu Tyr His180 185 190Ala Lys Ala Thr Glu His Leu Ser Thr Leu Ser Glu Lys Ala Lys Pro195 200 205Ala Leu Glu Asp Leu Arg Gln Gly Leu Leu Pro Val Leu Glu Ser Phe210 215 220Lys Val Ser Phe Leu Ser Ala Leu Glu Glu Tyr Thr Lys Lys Leu Asn225 230 235 240Thr Gln<210>7<211>396<212>PRT<213>Homo sapiens<400>7Met Phe Leu Lys Ala Val Val Leu Thr Leu Ala Leu Val Ala Val Ala1 5 10 15Gly Ala Arg Ala Glu Val Ser Ala Asp Gln Val Ala Thr Val Met Trp20 25 30
Asp Tyr Phe Ser Gln Leu Ser Asn Asn Ala Lys Glu Ala Val Glu His35 40 45Leu Gln Lys Ser Glu Leu Thr Gln Gln Leu Asn Ala Leu Phe Gln Asp50 55 60Lys Leu Gly Glu Val Asn Thr Tyr Ala Gly Asp Leu Gln Lys Lys Leu65 70 75 80Val Pro Phe Ala Thr Glu Leu His Glu Arg Leu Ala Lys Asp Ser Glu85 90 95Lys Leu Lys Glu Glu Ile Gly Lys Glu Leu Glu Glu Leu Arg Ala Arg100 105 110Leu Leu Pro His Ala Asn Glu Val Ser Gln Lys Ile Gly Asp Asn Leu115 120 125Arg Glu Leu Gln Gln Arg Leu Glu Pro Tyr Ala Asp Gln Leu Arg Thr130 135 140Gln Val Asn Thr Gln Ala Glu Gln Leu Arg Arg Gln Leu Thr Pro Tyr145 150 155 160Ala Gln Arg Met Glu Arg Val Leu Arg Glu Asn Ala Asp Ser Leu Gln165 170 175Ala Ser Leu Arg Pro His Ala Asp Glu Leu Lys Ala Lys Ile Asp Gln180 185 190Asn Val Glu Glu Leu Lys Gly Arg Leu Thr Pro Tyr Ala Asp Glu Phe195 200 205Lys Val Lys Ile Asp Gln Thr Val Glu Glu Leu Arg Arg Ser Leu Ala210 215 220Pro Tyr Ala Gln Asp Thr Gln Glu Lys Leu Asn His Gln Leu Glu Gly225 230 235 240Leu Thr Phe Gln Met Lys Lys Asn Ala Glu Glu Leu Lys Ala Arg Ile245 250 255Ser Ala Ser Ala Glu Glu Leu Arg Gln Arg Leu Ala Pro Leu Ala Glu
260 265 270Asp Val Arg Gly Asn Leu Arg Gly Asn Thr Glu Gly Leu Gln Lys Ser275 280 285Leu Ala Glu Leu Gly Gly His Leu Asp Gln Gln Val Glu Glu Phe Arg290 295 300Arg Arg Val Glu Pro Tyr Gly Glu Asn Phe Asn Lys Ala Leu Val Gln305 310 315 320Gln Met Glu Gln Leu Arg Thr Lys Leu Gly Pro His Ala Gly Asp Val325 330 335Glu Gly His Leu Ser Phe Leu Glu Lys Asp Leu Arg Asp Lys Val Asn340 345 350Ser Phe Phe Ser Thr Phe Lys Glu Lys Glu Ser Gln Asp Lys Thr Leu355 360 365Ser Leu Pro Glu Leu Glu Gln Gln Gln Glu Gln His Gln Glu Gln Gln370 375 380Gln Glu Gln Val Gln Met Leu Ala Pro Leu Glu Ser385 390 395<210>8<211>317<212>PRT<213>Homo sapiens<400>8Met Lys Val Leu Trp Ala Ala Leu Leu Val Thr Phe Leu Ala Gly Cys1 5 10 15Gln Ala Lys Val Glu Gln Ala Val Glu Thr Glu Pro Glu Pro Glu Leu20 25 30Arg Gln Gln Thr Glu Trp Gln Ser Gly Gln Arg Trp Glu Leu Ala Leu35 40 45Gly Arg Phe Trp Asp Tyr Leu Arg Trp Val Gln Thr Leu Ser Glu Gln50 55 60Val Gln Glu Glu Leu Leu Ser Ser Gln Val Thr Gln Glu Leu Arg Ala
65 70 75 80Leu Met Asp Glu Thr Met Lys Glu Leu Lys Ala Tyr Lys Ser Glu Leu85 90 95Glu Glu Gln Leu Thr Pro Val Ala Glu Glu Thr Arg Ala Arg Leu Ser100 105 110Lys Glu Leu Gln Ala Ala Gln Ala Arg Leu Gly Ala Asp Met Glu Asp115 120 125Val Cys Gly Arg Leu Val Gln Tyr Arg Gly Glu Val Gln Ala Met Leu130 135 140Gly Gln Ser Thr Glu Glu Leu Arg Val Arg Leu Ala Ser His Leu Arg145 150 155 160Lys Leu Arg Lys Arg Leu Leu Arg Asp Ala Asp Asp Leu Gln Lys Arg165 170 175Leu Ala Val Tyr Gln Ala Gly Ala Arg Glu Gly Ala Glu Arg Gly Leu180 185 190Ser Ala Ile Arg Glu Arg Leu Gly Pro Leu Val Glu Gln Gly Arg Val195 200 205Arg Ala Ala Thr Val Gly Ser Leu Ala Gly Gln Pro Leu Gln Glu Arg210 215 220Ala Gln Ala Trp Gly Glu Arg Leu Arg Ala Arg Met Glu Glu Met Gly225 230 235 240Ser Arg Thr Arg Asp Arg Leu Asp Glu Val Lys Glu Gln Val Ala Glu245 250 255Val Arg Ala Lys Leu Glu Glu Gln Ala Gln Gln Ile Arg Leu Gln Ala260 265 270Glu Ala Phe Gln Ala Arg Leu Lys Ser Trp Phe Glu Pro Leu Val Glu275 280 285Asp Met Gln Arg Gln Trp Ala Gly Leu Val Glu Lys Val Gln Ala Ala290 295 300
Val Gly Thr Ser Ala Ala Pro Val Pro Ser Asp Asn His305 310 315<210>9<211>262<212>PRT<213>Danio rerio<400>9Met Lys Phe Val Ala Leu Ala Leu Thr Leu Leu Leu Ala Leu Gly Ser1 5 10 15Gln Ala Asn Leu Phe Gln Ala Asp Ala Pro Thr Gln Leu Glu His Tyr20 25 30Lys Ala Ala Ala Leu Val Tyr Leu Asn Gln Val Lys Asp Gln Ala Glu35 40 45Lys Ala Leu Asp Asn Leu Asp Gly Thr Asp Tyr Glu Gln Tyr Lys Leu50 55 60Gln Leu Ser Glu Ser Leu Thr Lys Leu Gln Glu Tyr Ala Gln Thr Thr65 70 75 80Ser Gln Ala Leu Thr Pro Tyr Ala Glu Thr Ile Ser Thr Gln Leu Met85 90 95Glu Asn Thr Lys Gln Leu Arg Glu Arg Val Met Thr Asp Val Glu Asp100 105 110Leu Arg Ser Lys Leu Glu Pro His Arg Ala Glu Leu Tyr Thr Ala Leu115 120 125Gln Lys His Ile Asp Glu Tyr Arg Glu Lys Leu Glu Pro Val Phe Gln130 135 140Glu Tyr Ser Ala Leu Asn Arg Gln Asn Ala Glu Gln Leu Arg Ala Lys145 150 155 160Leu Glu Pro Leu Met Asp Asp Ile Arg Lys Ala Phe Glu Ser Asn Ile165 170 175Glu Glu Thr Lys Ser Lys Val Val Pro Met Val Glu Ala Val Arg Thr180 185 190
Lys Leu Thr Glu Arg Leu Glu Asp Leu Arg Thr Met Ala Ala Pro Tyr195 200 205Ala Glu Glu Tyr Lys Glu Gln Leu Val Lys Ala Val Glu Glu Ala Arg210 215 220Glu Lys Ile Ala Pro His Thr Gln Asp Leu Gln Thr Arg Met Glu Pro225 230 235 240Tyr Met Glu Asn Val Arg Thr Thr Phe Ala Gln Met Tyr Glu Thr Ile245 250 255Ala Lys Ala Ile Gln Ala260<210>10<211>259<212>PRT<213>Rattus norvegicus<400>10Met Lys Ala Ala Val Leu Ala Val Ala Leu Val Phe Leu Thr Gly Cys1 5 10 15Gln Ala Trp Glu Phe Trp Gln Gln Asp Glu Pro Gln Ser Gln Trp Asp20 25 30Arg Val Lys Asp Phe Ala Thr Val Tyr Val Asp Ala Val Lys Asp Ser35 40 45Gly Arg Asp Tyr Val Ser Gln Phe Glu Ser Ser Thr Leu Gly Lys Gln50 55 60Leu Asn Leu Asn Leu Leu Asp Asn Trp Asp Thr Leu Gly Ser Thr Val65 70 75 80Gly Arg Leu Gln Glu Gln Leu Gly Pro Val Thr Gln Glu Phe Trp Ala85 90 95Asn Leu Glu Lys Glu Thr Asp Trp Leu Arg Asn Glu Met Asn Lys Asp100 105 110Leu Glu Asn Val Lys Gln Lys Met Gln Pro His Leu Asp Glu Phe Gln115 120 125
Glu Lys Trp Asn Glu Glu Val Glu Ala Tyr Arg Gln Lys Leu Glu Pro130 135 140Leu Gly Thr Glu Leu His Lys Asn Ala Lys Glu Met Gln Arg His Leu145 150 155 160Lys Val Val Ala Glu Glu Phe Arg Asp Arg Met Arg Val Asn Ala Asp165 170 175Ala Leu Arg Ala Lys Phe Gly Leu Tyr Ser Asp Gln Met Arg Glu Asn180 185 190Leu Ala Gln Arg Leu Thr Glu Ile Arg Asn His Pro Thr Leu Ile Glu195 200 205Tyr His Thr Lys Ala Gly Asp His Leu Arg Thr Leu Gly Glu Lys Ala210 215 220Lys Pro Ala Leu Asp Asp Leu Gly Gln Gly Leu Met Pro Val Leu Glu225 230 235 240Ala Trp Lys Ala Lys Ile Met Ser Met Ile Asp Glu Ala Lys Lys Lys245 250 255Leu Asn Ala<210>11<211>265<212>PRT<213>Bos taurus<400>11Met Lys Ala Val Val Leu Thr Leu Ala Val Leu Phe Leu Thr Gly Ser1 5 10 15Gln Ala Arg His Phe Trp Gln Gln Asp Asp Pro Gln Ser Ser Trp Asp20 25 30Arg Val Lys Asp Phe Ala Thr Val Tyr Val Glu Ala Ile Lys Asp Ser35 40 45Gly Arg Asp Tyr Val Ala Gln Phe Glu Ala Ser Ala Leu Gly Lys Gln50 55 60
Leu Asn Leu Lys Leu Leu Asp Asn Trp Asp Thr Leu Ala Ser Thr Leu65 70 75 80Ser Lys Val Arg Glu Gln Leu Gly Pro Val Thr Gln Glu Phe Trp Asp85 90 95Asn Leu Glu Lys Glu Thr Ala Ser Leu Arg Gln Glu Met His Lys Asp100 105 110Leu Glu Glu Val Lys Gln Lys Val Gln Pro Tyr Leu Asp Glu Phe Gln115 120 125Lys Lys Trp His Glu Glu Val Glu Ile Tyr Arg Gln Lys Val Ala Pro130 135 140Leu Gly Glu Glu Phe Arg Glu Gly Ala Arg Gln Lys Val Gln Glu Leu145 150 155 160Gln Asp Lys Leu Ser Pro Leu Ala Gln Glu Leu Arg Asp Arg Ala Arg165 170 175Ala His Val Glu Thr Leu Arg Gln Gln Leu Ala Pro Tyr Ser Asp Asp180 185 190Leu Arg Gln Arg Leu Thr Ala Arg Leu Glu Ala Leu Lys Glu Gly Gly195 200 205Gly Ser Leu Ala Glu Tyr His Ala Lys Ala Ser Glu Gln Leu Lys Ala210 215 220Leu Gly Glu Lys Ala Lys Pro Val Leu Glu Asp Leu Arg Gln Gly Leu225 230 235 240Leu Pro Val Leu Glu Ser Leu Lys Val Ser Ile Leu Ala Ala Ile Asp245 250 255Glu Ala Ser Lys Lys Leu Asn Ala Gln260 265<210>12<211>264<212>PRT<213>Mus musculus<400>12
Met Lys Ala Val Val Leu Ala Val Ala Leu Val Phe Leu Thr Gly Ser1 5 10 15Gln Ala Trp His Val Trp Gln Gln Asp Glu Pro Gln Ser Gln Trp Asp20 25 30Lys Val Lys Asp Phe Ala Asn Val Tyr Val Asp Ala Val Lys Asp Ser35 40 45Gly Arg Asp Tyr Val Ser Gln Phe Glu Ser Ser Ser Leu Gly Gln Gln50 55 60Leu Asn Leu Asn Leu Leu Glu Asn Trp Asp Thr Leu Gly Ser Thr Val65 70 75 80Ser Gln Leu Gln Glu Arg Leu Gly Pro Leu Thr Arg Asp Phe Trp Asp85 90 95Asn Leu Glu Lys Glu Thr Asp Trp Val Arg Gln Glu Met Asn Lys Asp100 105 110Leu Glu Glu Val Lys Gln Lys Val Gln Pro Tyr Leu Asp Glu Phe Gln115 120 125Lys Lys Trp Lys Glu Asp Val Glu Leu Tyr Arg Gln Lys Val Ala Pro130 135 140Leu Gly Ala Glu Leu Gln Glu Ser Ala Arg Gln Lys Leu Gln Glu Leu145 150 155 160Gln Gly Arg Leu Ser Pro Val Ala Glu Glu Phe Arg Asp Arg Met Arg165 170 175Thr His Val Asp Ser Leu Arg Thr Gln Leu Ala Pro His Ser Glu Gln180 185 190Met Arg Glu Ser Leu Ala Gln Arg Leu Ala Glu Leu Lys Ser Asn Pro195 200 205Thr Leu Asn Glu Tyr His Thr Arg Ala Lys Thr His Leu Lys Thr Leu210 215 220Gly Glu Lys Ala Arg Pro Ala Leu Glu Asp Leu Arg His Ser Leu Met225 230 235 240
Pro Met Leu Glu Thr Leu Lys Thr Lys Ala Gln Ser Val Ile Asp Lys245 250 255Ala Ser Glu Thr Leu Thr Ala Gln260<210>13<211>56<212>PRT<213>Ovis aries<400>13Leu Asp Asn Trp Asp Ser Leu Ala Ser Thr Leu Ser Lys Val Arg Glu1 5 10 15Gln Leu Gly Pro Val Thr Gln Glu Phe Trp Asp Asn Leu Glu Lys Glu20 25 30Thr Ala Ser Leu Arg Gln Glu Met His Lys Asp Leu Glu Glu Ala Arg35 40 45Gln Lys Val Gln Pro Tyr Leu Asp50 55<210>14<211>239<212>PRT<213>Sus scrofa<400>14Met Lys Ala Val Val Leu Thr Leu Ala Val Leu Phe Leu Thr Gly Ser1 5 10 15Gln Ala Arg His Phe Trp Gln Gln Asp Asp Pro Gln Ser Pro Trp Asp20 25 30Arg Val Lys Asp Phe Ala Thr Val Tyr Val Asp Ala Ile Lys Asp Ser35 40 45Gly Arg Asp Tyr Val Ala Gln Phe Glu Ala Ser Ala Leu Gly Lys His50 55 60Leu Asn Leu Lys Leu Leu Asp Asn Trp Asp Ser Leu Gly Ser Thr Phe65 70 75 80
Thr Lys Val Arg Glu Gln Leu Gly Pro Val Thr Gln Glu Phe Trp Asp85 90 95Asn Leu Glu Lys Glu Thr Glu Ala Leu Arg Gln Glu Met Ser Lys Asp100 105 110Leu Glu Glu Val Lys Lys Lys Val Gln Pro Tyr Leu Asp Asp Phe Gln115 120 125Asn Lys Trp Gln Glu Glu Met Glu Thr Tyr Arg Gln Lys Met Ala Pro130 135 140Leu Gly Ala Glu Phe Arg Glu Gly Ala Arg Gln Lys Val Gln Glu Leu145 150 155 160Gln Glu Lys Leu Ser Pro Leu Ala Glu Glu Leu Arg Asp Arg Leu Arg165 170 175Ala His Val Glu Ala Leu Arg Gln His Val Ala Pro Tyr Ser Asp Asp180 185 190Leu Arg Gln Arg Met Ala Ala Arg Phe Glu Ala Leu Lys Glu Gly Gly195 200 205Gly Ser Leu Ala Glu Tyr Gln Ala Lys Ala Gln Glu Gln Lys Val Ser210 215 220Ile Leu Ala Ala Ile Asp Glu Ala Ser Lys Lys Leu Asn Ala Gln225 230 235<210>15<211>174<212>PRT<213>Cyprinus carpio<400>15Leu Gly Gln Ser Val Asp Asn Leu His Gly Tyr Phe Gln Asn Gly Phe1 5 10 15Gln Ala Ile Thr Pro Ile Gly Asp Gln Val Leu Glu Ala Thr Lys Asp20 25 30Thr Arg Glu Lys Leu Val Lys Asp Val Glu Glu Leu Arg Lys Lys Ile35 40 45
Glu Pro Met Arg Ala Glu Leu Arg Gln Val Leu Glu Lys His Leu Gln50 55 60Glu Tyr Arg Asp Glu Leu Lys Pro Phe Val Glu Glu Tyr Leu Thr Lys65 70 75 80His Gln Lys Phe Leu Glu Glu Met Arg Ile Lys Leu Glu Pro Val Val85 90 95Lys Ser Leu Arg Glu Lys Phe Gly Pro Asn Trp Glu Glu Thr Lys Ser100 105 110Lys Leu Met Pro Ile Leu Glu Ala Val Arg Glu Lys Val Ala Glu His115 120 125Leu Gln Asp Leu Lys Lys Leu Leu Glu Pro Tyr Met Gln Asp Tyr Arg130 135 140Glu Gln Met Glu Lys Gly Ala Gln Glu Phe Arg Gln Ser Val Lys Ser145 150 155 160Gly Glu Leu Arg Lys Lys Met Asn Glu Leu Gly Arg Arg Arg165 170<210>16<211>264<212>PRT<213>Gallus gallus<400>16Met Arg Gly Val Leu Val Thr Leu Ala Val Leu Phe Leu Thr Gly Thr1 5 10 15Gln Ala Arg Ser Phe Trp Gln His Asp Glu Pro Gln Thr Pro Leu Asp20 25 30Arg Ile Arg Asp Met Val Asp Val Tyr Leu Glu Thr Val Lys Ala Ser35 40 45Gly Lys Asp Ala Ile Ala Gln Phe Glu Ser Ser Ala Val Gly Lys Gln50 55 60Leu Asp Leu Lys Leu Ala Asp Asn Leu Asp Thr Leu Ser Ala Ala Ala65 70 75 80
Ala Lys Leu Arg Glu Asp Met Ala Pro Tyr Tyr Lys Glu Val Arg Glu85 90 95Met Trp Leu Lys Asp Thr Glu Ala Leu Arg Ala Glu Leu Thr Lys Asp100 105 110Leu Glu Glu Val Lys Glu Lys Ile Arg Pro Phe Leu Asp Gln Phe Ser115 120 125Ala Lys Trp Thr Glu Glu Leu Glu Gln Tyr Arg Gln Arg Leu Thr Pro130 135 140Val Ala Gln Glu Leu Lys Glu Leu Thr Lys Gln Lys Val Glu Leu Met145 150 155 160Gln Ala Lys Leu Thr Pro Val Ala Glu Glu Ala Arg Asp Arg Leu Arg165 170 175Gly His Val Glu Glu Leu Arg Lys Asn Leu Ala Pro Tyr Ser Asp Glu180 185 190Leu Arg Gln Lys Leu Ser Gln Lys Leu Glu Glu Ile Arg Glu Lys Gly195 200 205Ile Pro Gln Ala Ser Glu Tyr Gln Ala Lys Val Met Glu Gln Leu Ser210 215 220Asn Leu Arg Glu Lys Met Thr Pro Leu Val Gln Glu Phe Arg Glu Arg225 230 235 240Leu Thr Pro Tyr Ala Glu Asn Leu Lys Asn Arg Leu Ile Ser Phe Leu245 250 255Asp Glu Leu Gln Lys Ser Val Ala260<210>17<211>266<212>PRT<213>Oryctolagus cuniculus<400>17Met Lys Ala Val Val Leu Thr Leu Ala Val Leu Phe Leu Thr Gly Ser1 5 10 15
Gln Ala Arg His Phe Trp Gln Arg Asp Glu Pro Arg Ser Ser Trp Asp20 25 30Lys Ile Lys Asp Phe Ala Thr Val Tyr Val Asp Thr Val Lys Asp Ser35 40 45Gly Arg Glu Tyr Val Ala Gln Phe Glu Ala Ser Ala Phe Gly Lys Gln50 55 60Leu Asn Leu Lys Leu Leu Asp Asn Trp Asp Ser Leu Ser Ser Thr Val65 70 75 80Ser Lys Leu Gln Glu Gln Leu Gly Pro Val Thr Gln Glu Phe Trp Asp85 90 95Asn Leu Glu Lys Glu Thr Glu Gly Leu Arg Glu Glu Met Asn Lys Asp100 105 110Leu Gln Glu Val Arg Gln Lys Val Gln Pro Tyr Leu Asp Glu Phe Gln115 120 125Lys Lys Trp Gln Glu Glu Val Glu Arg Tyr Arg Gln Lys Val Glu Pro130 135 140Leu Gly Ala Glu Leu Arg Glu Ser Ala Arg Gln Lys Leu Thr Glu Leu145 150 155 160Gln Glu Lys Leu Ser Pro Leu Ala Glu Glu Leu Arg Asp Ser Ala Arg165 170 175Thr His Val Asp Thr Leu Arg Thr Lys Leu Ala Pro Tyr Ser Asn Glu180 185 190Leu Gln Gln Arg Leu Ala Ala Arg Leu Glu Ser Ile Lys Glu Gly Gly195 200 205Gly Ala Ser Leu Ala Glu Tyr Gln Ala Lys Ala Arg Glu His Leu Ser210 215 220Val Leu Ser Glu Lys Ala Arg Pro Ala Leu Glu Asp Leu Arg Gln Gly225 230 235 240Leu Leu Pro Val Leu Glu Ser Phe Lys Ala Ser Val Gln Asn Val Leu245 250 255
Asp Glu Ala Thr Lys Lys Leu Asn Thr Gln260 265<210>18<211>267<212>PRT<213>Macaca fascicularis<400>18Met Lys Ala Thr Val Leu Thr Leu Ala Val Leu Phe Leu Thr Gly Ser1 5 10 15Gln Ala Arg His Phe Trp Gln Gln Asp Glu Pro Pro Gln Thr Pro Trp20 25 30Asp Arg Val Lys Asp Leu Val Thr Val Tyr Val Glu Ala Leu Lys Asp35 40 45Ser Gly Lys Asp Tyr Val Ser Gln Phe Glu Gly Ser Ala Leu Gly Lys50 55 60Gln Leu Asn Leu Lys Leu Leu Asp Asn Trp Asp Ser Val Thr Ser Thr65 70 75 80Val Ser Lys Leu Arg Glu Gln Leu Gly Pro Val Thr Gln Glu Phe Trp85 90 95Asp Asn Leu Glu Lys Glu Thr Glu Gly Leu Arg Gln Glu Met Ser Lys100 105 110Asp Leu Glu Glu Val Lys Ala Lys Val Gln Pro Tyr Leu Asp Asp Phe115 120 125Gln Lys Lys Trp Gln Glu Glu Met Glu Leu Tyr Arg Gln Lys Val Glu130 135 140Pro Leu Arg Ala Glu Leu His Glu Gly Thr Arg Gln Lys Leu His Glu145 150 155 160Leu His Glu Lys Leu Ser Pro Leu Gly Glu Glu Val Arg Asp Arg Ala165 170 175Arg Ala His Val Asp Ala Leu Arg Thr His Leu Ala Pro Tyr Ser Asp180 185 190
Glu Leu Arg Gln Arg Leu Ala Ala Arg Leu Glu Ala Leu Lys Glu Asn195 200 205Gly Gly Ala Arg Leu Ala Glu Tyr His Ala Lys Ala Ser Glu His Leu210 215 220Ser Thr Leu Ser Glu Lys Ala Lys Pro Ala Leu Glu Asp Leu Arg Gln225 230 235 240Gly Leu Leu Pro Val Leu Glu Ser Phe Lys Val Ser Phe Leu Ser Ala245 250 255Leu Glu Glu Tyr Thr Lys Lys Leu Ser Thr Gln260 265<210>19<211>264<212>PRT<213>Coturniz japonica<400>19Met Arg Gly Val Leu Val Thr Leu Ala Val Leu Phe Leu Thr Gly Thr1 5 10 15Gln Ala Arg Ser Phe Trp Gln His Asp Asp Pro Gln Thr Pro Leu Asp20 25 30Arg Ile Arg Asp Met Leu Asp Val Tyr Leu Glu Thr Val Lys Ala Ser35 40 45Gly Lys Asp Ala Ile Ser Gln Phe Glu Ser Ser Ala Val Gly Lys Gln50 55 60Leu Asp Leu Lys Leu Ala Asp Asn Leu Asp Thr Leu Ser Ala Ala Ala65 70 75 80Ala Lys Leu Arg Glu Asp Met Thr Pro Tyr Tyr Arg Glu Val Arg Glu85 90 95Met Trp Leu Lys Asp Thr Glu Ala Leu Arg Ala Glu Leu Thr Lys Asp100 105 110Leu Glu Glu Val Lys Glu Lys Ile Arg Pro Phe Leu Asp Gln Phe Ser115 120 125
Ala Lys Trp Thr Glu Glu Val Glu Gln Tyr Arg Gln Arg Leu Ala Pro130 135 140Val Ala Gln Glu Leu Lys Asp Leu Thr Lys Gln Lys Val Glu Leu Met145 150 155 160Gln Ala Lys Leu Thr Pro Val Ala Glu Glu Val Arg Asp Arg Leu Arg165 170 175Glu Gln Val Glu Glu Leu Arg Lys Asn Leu Ala Pro Tyr Ser Ser Glu180 185 190Leu Arg Gln Lys Leu Ser Gln Lys Leu Glu Glu Ile Arg Glu Arg Gly195 200 205Ile Pro Gln Ala Ser Glu Tyr Gln Ala Lys Val Val Glu Gln Leu Ser210 215 220Asn Leu Arg Glu Lys Met Thr Pro Leu Val Gln Glu Phe Lys Glu Arg225 230 235 240Leu Thr Pro Tyr Ala Glu Asn Leu Lys Asn Arg Leu Ile Asp Leu Leu245 250 255Asp Glu Val Gln Lys Thr Met Ala260<210>20<211>266<212>PRT<213>Canis familiaris<400>20Met Lys Ala Ala Leu Leu Thr Leu Ala Val Leu Phe Leu Thr Gly Ser1 5 10 15Gln Ala Arg His Phe Trp Gln Gln Asp Glu Pro Gln Ser Pro Trp Asp20 25 30Arg Val Lys Asp Leu Ala Thr Val Tyr Val Asp Ala Val Lys Asp Ser35 40 45Gly Arg Asp Tyr Val Ala Gln Phe Glu Ala Ser Ala Leu Gly Lys Gln50 55 60
Leu Asn Leu Lys Leu Leu Asp Asn Trp Asp Ser Leu Ser Ser Thr Val65 70 75 80Thr Lys Leu Arg Glu Gln Ile Gly Pro Val Thr Gln Glu Phe Trp Asp85 90 95Asn Leu Glu Lys Glu Thr Glu Val Leu Arg Gln Glu Met Ser Lys Asp100 105 110Leu Glu Glu Val Lys Gln Lys Val Gln Pro Tyr Leu Asp Asp Phe Gln115 120 125Lys Lys Trp Gln Glu Glu Val Glu Leu Tyr Arg Gln Lys Val Ala Pro130 135 140Leu Gly Ser Glu Leu Arg Glu Gly Ala Arg Gln Lys Leu Gln Glu Leu145 150 155 160Gln Glu Lys Leu Ser Pro Leu Ala Glu Glu Leu Arg Asp Arg Ala Arg165 170 175Thr His Val Asp Ala Leu Arg Ala Gln Leu Ala Pro Tyr Ser Asp Asp180 185 190Leu Arg Glu Arg Leu Ala Ala Arg Leu Glu Ala Leu Lys Glu Gly Gly195 200 205Gly Ala Ser Leu Ala Glu Tyr His Ala Arg Ala Ser Glu Gln Leu Ser210 215 220Ala Leu Gly Glu Lys Ala Arg Pro Ala Leu Glu Asp Leu Arg Gln Gly225 230 235 240Leu Leu Pro Val Leu Glu Ser Phe Lys Val Ser Leu Leu Ala Ala Ile245 250 255Asp Glu Ala Thr Lys Lys Leu Asn Ala Gln260 265<210>21<211>265<212>PRT<213>Tupaia belangeri<400>21
Met Lys Ala Val Val Leu Thr Leu Ala Val Leu Phe Leu Thr Gly Ser1 5 10 15Gln Ala Arg His Phe Trp Gln Gln Asp Glu Pro Gln Ser Ser Trp Asp20 25 30Arg Val Arg Asp Leu Ala Asn Val Tyr Val Asp Ala Val Lys Glu Ser35 40 45Gly Arg Glu Tyr Val Ser Gln Leu Glu Ala Ser Ala Leu Gly Lys Gln50 55 60Leu Asn Leu Lys Leu Val Asp Asn Trp Asp Thr Leu Gly Ser Thr Phe65 70 75 80Gln Lys Val His Glu His Leu Gly Pro Val Ala Gln Glu Phe Trp Glu85 90 95Lys Leu Glu Lys Glu Thr Glu Glu Leu Arg Arg Glu Ile Asn Lys Asp100 105 110Leu Glu Asp Val Arg Gln Lys Thr Gln Pro Phe Leu Asp Glu Ile Gln115 120 125Lys Lys Trp Gln Glu Asp Leu Glu Arg Tyr Arg Gln Lys Val Glu Pro130 135 140Leu Ser Ala Gln Leu Arg Glu Gly Ala Arg Gln Lys Leu Met Glu Leu145 150 155 160Gln Glu Gln Val Thr Pro Leu Gly Glu Asp Leu Arg Asp Ser Val Arg165 170 175Ala Tyr Ala Asp Thr Leu Arg Thr Gln Leu Ala Pro Tyr Ser Glu Gln180 185 190Met Arg Lys Thr Leu Gly Ala Arg Leu Glu Ala Ile Lys Glu Gly Gly195 200 205Ser Ala Ser Leu Ala Glu Tyr His Ala Lys Ala Ser Glu Gln Leu Ser210 215 220Ala Leu Gly Glu Lys Ala Lys Pro Val Leu Glu Asp Ile His Gln Gly225 230 235 240
Leu Met Pro Met Trp Glu Ser Phe Lys Thr Gly Val Leu Asn Val Ile245 250 255Asp Glu Ala Ala Lys Lys Leu Thr Ala260 265<210>22<211>264<212>PRT<213>Anus platurhynchos<400>22Met Arg Val Val Val Val Thr Leu Ala Leu Leu Phe Leu Thr Gly Thr1 5 10 15Gln Ala Arg Tyr Phe Trp Gln His Asp Glu Pro Gln Ala Pro Leu Asp20 25 30Arg Leu Arg Asp Leu Val Asp Val Tyr Leu Glu Thr Val Lys Ala Ser35 40 45Gly Lys Asp Ala Ile Ala Gln Phe Glu Ala Ser Ala Val Gly Lys Gln50 55 60Leu Asp Leu Lys Leu Ala Asp Asn Leu Asp Thr Leu Gly Ala Ala Ala65 70 75 80Ala Lys Leu Arg Glu Asp Met Ala Pro Tyr Tyr Lys Glu Val Arg Glu85 90 95Met Trp Leu Lys Asp Thr Glu Ser Leu Arg Ala Glu Leu Thr Lys Asp100 105 110Leu Glu Glu Val Lys Glu Lys Ile Arg Pro Phe Leu Asp Gln Phe Ser115 120 125Ala Lys Trp Thr Glu Glu Leu Glu Gln Tyr Arg Gln Arg Leu Ala Pro130 135 140Val Ala Glu Glu Leu Lys Glu Leu Thr Lys Gln Lys Val Glu Leu Met145 150 155 160Gln Gln Lys Leu Thr Pro Val Ala Glu Glu Ala Arg Asp Arg Leu Arg165 170 175
Gly His Val Glu Glu Leu Arg Lys Asn Leu Ala Pro Tyr Ser Asp Glu180 185 190Leu Arg Gln Lys Leu Ser Gln Lys Leu Glu Glu Ile Arg Glu Lys Gly195 200 205Ile Pro Gln Ala Ala Glu Tyr Gln Ala Lys Val Val Glu Gln Leu Ser210 215 220Asn Leu Arg Glu Lys Met Thr Pro Leu Val Gln Asp Phe Lys Glu Arg225 230 235 240Leu Thr Pro Tyr Ala Glu Asn Leu Lys Thr Arg Phe Ile Ser Leu Leu245 250 255Asp Glu Leu Gln Lys Thr Val Ala260<210>23<211>267<212>PRT<213>Papio anubis<400>23Met Lys Ala Thr Val Leu Thr Leu Ala Val Leu Phe Leu Thr Gly Ser1 5 10 15Gln Ala Arg His Phe Trp Gln Gln Asp Glu Pro Pro Gln Thr Pro Trp20 25 30Asp Arg Val Lys Asp Leu Val Thr Val Tyr Val Glu Ala Leu Lys Asp35 40 45Ser Gly Lys Asp Tyr Val Ser Gln Phe Glu Gly Ser Ala Leu Gly Lys50 55 60Gln Leu Asn Leu Lys Leu Leu Asp Asn Trp Asp Ser Val Thr Ser Thr65 70 75 80Val Ser Lys Leu Arg Glu Gln Leu Gly Pro Val Thr Gln Glu Phe Trp85 90 95Asp Asn Leu Glu Lys Glu Thr Glu Gly Leu Arg Gln Glu Met Ser Lys100 105 110
Asp Leu Glu Glu Val Lys Ala Lys Val Gln Pro Tyr Leu Asp Asp Phe115 120 125Gln Lys Lys Trp Gln Glu Glu Met Glu Leu Tyr Arg Gln Lys Val Glu130 135 140Pro Leu Arg Ala Glu Leu His Glu Gly Thr Arg Gln Lys Leu His Glu145 150 155 160Leu His Glu Lys Leu Ser Pro Leu Gly Glu Glu Val Arg Asp Arg Ala165 170 175Arg Ala His Val Asp Ala Leu Arg Thr His Leu Ala Pro Tyr Ser Asp180 185 190Glu Leu Arg Gln Arg Leu Ala Ala Arg Leu Glu Ala Leu Lys Glu Asn195 200 205Gly Gly Ala Arg Leu Ala Glu Tyr His Ala Lys Ala Ser Glu His Leu210 215 220Ser Thr Leu Ser Glu Lys Ala Lys Pro Ala Leu Glu Asp Leu Arg Gln225 230 235 240Gly Leu Leu Pro Val Leu Glu Ser Phe Lys Val Ser Phe Leu Ser Ala245 250 255Leu Glu Glu Tyr Thr Lys Lys Leu Ser Thr Gln260 265<210>24<211>1420<212>PRT<213>Macaca mulatta<400>24Pro Asn Val Arg Trp Glu Tyr Cys Asn Leu Thr Gln Cys Ser Asp Ala1 5 10 15Glu Gly Thr Ala Val Ala Pro Pro Asn Val Thr Pro Val Pro Ser Leu20 25 30Glu Ala Pro Ser Glu Gln Ala Pro Thr Glu Gln Arg Pro Gly Val Gln35 40 45
Glu Cys Tyr His Gly Asn Gly Gln Ser Tyr Arg Gly Thr Tyr Phe Thr50 55 60Thr Val Thr Gly Arg Thr Cys Gln Ala Trp Ser Ser Met Thr Pro His65 70 75 80Ser His Ser Arg Thr Pro Glu Asn Tyr Pro Asn Gly Gly Leu Ile Arg85 90 95Asn Tyr Cys Arg Asn Pro Asp Pro Val Ala Ala Pro Tyr Cys Tyr Thr100 105 110Met Asp Pro Asn Val Arg Trp Glu Tyr Cys Asn Leu Thr Gln Cys Ser115 120 125Asp Ala Glu Gly Ile Ala Val Thr Pro Leu Thr Val Thr Pro Val Pro130 135 140Ser Leu Glu Ala Pro Ser Lys Gln Ala Pro Thr Glu Gln Arg Pro Gly145 150 155 160Val Gln Glu Cys Tyr His Gly Asn Gly Gln Ser Tyr Arg Gly Thr Tyr165 170 175Phe Thr Thr Val Thr Gly Arg Thr Cys Gln Ala Trp Ser Ser Met Thr180 185 190Pro His Ser His Ser Arg Thr Pro Glu Asn Tyr Pro Asn Gly Gly Leu195 200 205Ile Arg Asn Tyr Cys Arg Asn Pro Asp Pro Val Ala Ala Pro Tyr Cys210 215 220Tyr Thr Met Asp Pro Asn Val Arg Trp Glu Tyr Cys Asn Leu Thr Gln225 230 235 240Cys Ser Asp Ala Glu Gly Thr Ala Val Ala Pro Pro Asn Val Thr Pro245 250 255Val Pro Ser Leu Glu Ala Pro Ser Glu Gln Ala Pro Thr Glu Gln Arg260 265 270Ser Gly Val Gln Glu Cys Tyr His Gly Asn Gly Gln Ser Tyr Arg Gly
275 280 285Thr Tyr Phe Thr Thr Val Thr Gly Arg Thr Cys Gln Ala Trp Ser Ser290 295 300Met Lys Pro His Ser His Ser Arg Thr Pro Glu Asn Tyr Pro Asn Gly305 310 315 320Gly Leu Ile Arg Asn Tyr Cys Arg Asn Pro Asp Pro Val Ala Ala Pro325 330 335Tyr Cys Tyr Thr Met Asp Pro Asn Val Arg Trp Glu Tyr Cys Asn Leu340 345 350Thr Gln Cys Ser Asp Ala Glu Gly Thr Ala Val Ala Pro Pro Asn Val355 360 365Thr Pro Val Pro Ser Leu Glu Ala Pro Ser Glu Gln Ala Pro Thr Glu370 375 380Gln Arg Leu Gly Val Gln Glu Cys Tyr His Ser Asn Gly Gln Ser Tyr385 390 395 400Arg Gly Thr Tyr Phe Thr Thr Val Thr Gly Arg Thr Cys Gln Ala Trp405 410 415Ser Ser Met Thr Pro His Ser His Ser Arg Thr Pro Glu Asn Tyr Pro420 425 430Asn Ala Gly Leu Val Lys Asn Tyr Cys Arg Asn Pro Asp Pro Val Ala435 440 445Ala Pro Trp Cys Tyr Thr Thr Asp Pro Ser Val Arg Trp Glu Tyr Cys450 455 460Asn Leu Thr Arg Cys Ser Asp Ala Glu Gly Thr Ala Val Met Pro Pro465 470 475 480Asn Ile Ile Pro Val Pro Ser Leu Glu Ala Phe Leu Glu Gln Glu Pro485 490 495Thr Glu Glu Thr Pro Gly Val Gln Glu Cys Tyr Tyr His Tyr Gly Gln500 505 510
Ser Tyr Arg Gly Thr Tyr Ser Thr Thr Val Thr Gly Arg Thr Cys Gln515 520 525Ala Trp Ser Ser Met Thr Pro His Gln His Ser Arg Thr Pro Lys Asn530 535 540Tyr Pro Asn Ala Gly Leu Thr Arg Asn Tyr Cys Arg Asn Pro Asp Ala545 550 555 560Glu Ile Arg Pro Trp Cys Tyr Thr Met Asp Pro Ser Val Arg Trp Glu565 570 575Tyr Cys Asn Leu Thr Gln Cys Leu Val Thr Glu Ser Ser Val Leu Glu580 585 590Thr Leu Thr Val Val Pro Asp Pro Ser Thr Gln Ala Ser Ser Glu Glu595 600 605Ala Pro Thr Glu Gln Ser Pro Glu Val Gln Asp Cys Tyr His Gly Asp610 615 620Gly Gln Ser Tyr Arg Gly Ser Phe Ser Thr Thr Val Thr Gly Arg Thr625 630 635 640Cys Gln Ser Trp Ser Ser Met Thr Pro His Trp His Gln Arg Thr Thr645 650 655Glu Tyr Tyr Pro Asp Gly Gly Leu Thr Arg Asn Tyr Cys Arg Asn Pro660 665 670Asp Ala Glu Ile Arg Pro Trp Cys Tyr Thr Met Asp Pro Ser Val Arg675 680 685Trp Glu Tyr Cys Asn Leu Thr Gln Cys Pro Val Thr Glu Ser Ser Val690 695 700Leu Ala Thr Ser Met Ala Val Ser Glu Gln Ala Pro Met Glu Gln Ser705 710 715 720Pro Gly Val Gln Asp Cys Tyr His Gly Asp Gly Gln Ser Tyr Arg Gly725 730 735Ser Phe Ser Thr Thr Val Thr Gly Arg Ile Cys Gln Ser Trp Ser Ser740 745 750
Met Thr Pro His Trp His Gln Arg Thr Ile Glu Tyr Tyr Pro Asn Gly755 760 765Gly Leu Thr Lys Asn Tyr Cys Arg Asn Pro Asp Ala Glu Ile Arg Pro770 775 780Trp Cys Tyr Thr Met Asp Pro Arg Val Arg Trp Glu Tyr Cys Asn Leu785 790 795 800Thr Gln Cys Val Val Met Glu Ser Ser Val Leu Ala Thr Pro Met Val805 810 815Val Pro Val Pro Ser Arg Glu Val Pro Ser Glu Glu Ala Pro Thr Glu820 825 830Asn Ser Pro Gly Val Gln Asp Cys Tyr Gln Gly Asp Gly Gln Ser Tyr835 840 845Arg Gly Thr Phe Ser Thr Thr Ile Thr Gly Arg Thr Cys Gln Ser Trp850 855 860Leu Ser Met Thr Pro His Arg His Arg Arg Ile Pro Leu Arg Tyr Pro865 870 875 880Asn Ala Gly Leu Thr Arg Asn Tyr Cys Arg Asn Arg Asp Ala Glu Ile885 890 895Arg Pro Trp Cys Tyr Thr Met Asp Pro Ser Val Arg Trp Glu Tyr Cys900 905 910Asn Leu Thr Gln Cys Pro Val Thr Glu Ser Ser Val Leu Thr Thr Pro915 920 925Thr Val Val Pro Val Pro Ser Thr Glu Ala Pro Ser Glu Gln Ala Pro930 935 940Pro Glu Lys Ser Pro Val Val Gln Asp Cys Tyr His Gly Asp Gly Gln945 950 955 960Ser Tyr Arg Gly Thr Ser Ser Thr Thr Val Thr Gly Arg Asn Cys Gln965 970 975Ser Trp Ser Ser Met Ile Pro His Trp His Gln Arg Thr Pro Glu Asn980 985 990
Tyr Pro Asn Ala Gly Leu Thr Arg Asn Tyr Cys Arg Asn Pro Asp Ser995 1000 1005Gly Lys His Pro Trp Cys Tyr Thr Thr Asp Pro Cys Val Arg Trp1010 1015 1020Glu Tyr Cys Asn Leu Thr Gln Cys Ser Glu Thr Glu Ser Gly Val1025 1030 1035Leu Glu Thr Pro Thr Val Val Pro Val Pro Ser Met Glu Ala His1040 1045 1050Ser Glu Ala Ala Pro Thr Glu Gln Thr Pro Val Val Gln Gln Cys1055 1060 1065Tyr His Gly Asn Gly Gln Ser Tyr Arg Gly Thr Phe Ser Thr Thr1070 1075 1080Val Thr Gly Arg Thr Cys Gln Ser Trp Ser Ser Met Thr Pro His1085 1090 1095Gln His Lys Arg Thr Pro Glu Asn His Pro Asn Asp Asp Leu Thr1100 1105 1110Met Asn Tyr Cys Arg Asn Pro Asp Ala Asp Thr Gly Pro Trp Cys1115 1120 1125Phe Thr Met Asp Pro Ser Val Arg Arg Glu Tyr Cys Asn Leu Thr1130 1135 1140Arg Cys Ser Asp Thr Glu Gly Thr Val Val Thr Pro Pro Thr Val1145 1150 1155Ile Pro Val Pro Ser Leu Glu Ala Pro Ser Glu Gln Ala Ser Ser1160 1165 1170Ser Phe Asp Cys Gly Lys Pro Gln Val Glu Pro Lys Lys Cys Pro1175 1180 1185Gly Ser Ile Val Gly Gly Cys Val Ala His Pro His Ser Trp Pro1190 1195 1200Trp Gln Val Ser Leu Arg Thr Arg Phe Gly Lys His Phe Cys Gly
1205 1210 1215Gly Thr Leu Ile Ser Pro Glu Trp Val Leu Thr Ala Ala Cys Cys1220 1225 1230Leu Glu Thr Phe Ser Arg Pro Ser Phe Tyr Lys Val Ile Leu Gly1235 1240 1245Ala His Gln Glu Val Asn Leu Glu Ser His Val Gln Glu Ile Glu1250 1255 1260Val Ser Arg Leu Phe Leu Glu Pro Ile Gly Ala Asp Ile Ala Leu1265 1270 1275Leu Lys Leu Ser Arg Pro Ala Ile Ile Thr Asp Lys Val Ile Pro1280 1285 1290Ala Cys Leu Pro Ser Pro Asn Tyr Val Ile Thr Ala Trp Thr Glu1295 1300 1305Cys Tyr Ile Thr Gly Trp Gly Glu Thr Gln Gly Thr Phe Gly Ala1310 1315 1320Gly Leu Leu Lys Glu Ala Gln Leu His Val Ile Glu Asn Thr Val1325 1330 1335Cys Asn His Tyr Glu Phe Leu Asn Gly Arg Val Lys Ser Thr Glu1340 1345 1350Leu Cys Ala Gly His Leu Ala Gly Gly Thr Asp Arg Cys Gln Gly1355 1360 1365Asp Asn Gly Gly Pro Val Val Cys Phe Asp Lys Asp Lys Tyr Ile1370 1375 1380Leu Arg Gly Ile Thr Ser Trp Gly Pro Gly Cys Ala Cys Pro Asn1385 1390 1395Lys Pro Gly Val Tyr Val Arg Val Ser Ser Phe Val Thr Trp Ile1400 1405 1410Glu Gly Val Met Arg Asn Asn1415 1420
<210>25<211>391<212>PRT<213>Rattus norvegicus<400>25Met Phe Leu Lys Ala Val Val Leu Thr Val Ala Leu Val Ala Ile Thr1 5 10 15Gly Thr Gln Ala Glu Val Thr Ser Asp Gln Val Ala Asn Val Met Trp20 25 30Asp Tyr Phe Thr Gln Leu Ser Asn Asn Ala Lys Glu Ala Val Glu Gln35 40 45Leu Gln Lys Thr Asp Val Thr Gln Gln Leu Asn Thr Leu Phe Gln Asp50 55 60Lys Leu Gly Asn Ile Asn Thr Tyr Ala Asp Asp Leu Gln Asn Lys Leu65 70 75 80Val Pro Phe Ala Val Gln Leu Ser Gly His Leu Thr Lys Glu Thr Glu85 90 95Arg Val Arg Glu Glu Ile Gln Lys Glu Leu Glu Asp Leu Arg Ala Asn100 105 110Met Met Pro His Ala Asn Lys Val Ser Gln Met Phe Gly Asp Asn Val115 120 125Gln Lys Leu Gln Glu His Leu Arg Pro Tyr Ala Thr Asp Leu Gln Ala130 135 140Gln Ile Asn Ala Gln Thr Gln Asp Met Lys Arg Gln Leu Thr Pro Tyr145 150 155 160Ile Gln Arg Met Gln Thr Thr Ile Gln Asp Asn Val Glu Asn Leu Gln165 170 175Ser Ser Met Val Pro Phe Ala Asn Glu Leu Lys Glu Lys Phe Asn Gln180 185 190Asn Met Glu Gly Leu Lys Gly Gln Leu Thr Pro Arg Ala Asn Glu Leu195 200 205
Lys Ala Thr Ile Asp Gln Asn Leu Glu Asp Leu Arg Ser Arg Leu Ala210 215 220Pro Leu Ala Glu Gly Val Gln Glu Lys Leu Asn His Gln Met Glu Gly225 230 235 240Leu Ala Phe Gln Met Lys Lys Asn Ala Glu Glu Leu His Thr Lys Val245 250 255Ser Thr Asn Ile Asp Gln Leu Gln Lys Asn Leu Ala Pro Leu Val Glu260 265 270Asp Val Gln Ser Lys Leu Lys Gly Asn Thr Glu Gly Leu Gln Lys Ser275 280 285Leu Glu Asp Leu Asn Lys Gln Leu Asp Gln Gln Val Glu Val Phe Arg290 295 300Arg Ala Val Glu Pro Leu Gly Asp Lys Phe Asn Met Ala Leu Val Gln305 310 315 320Gln Met Glu Lys Phe Arg Gln Gln Leu Gly Ser Asp Ser Gly Asp Val325 330 335Glu Ser His Leu Ser Phe Leu Glu Lys Asn Leu Arg Glu Lys Val Ser340 345 350Ser Phe Met Ser Thr Leu Gln Lys Lys Gly Ser Pro Asp Gln Pro Leu355 360 365Ala Leu Pro Leu Pro Glu Gln Val Gln Glu Gln Val Gln Glu Gln Val370 375 380Gln Pro Lys Pro Leu Glu Ser385 390<210>26<211>375<212>PRT<213>Mus musculus<400>26Met Phe Leu Lys Ala Ala Val Leu Thr Leu Ala Leu Val Ala Ile Thr1 5 10 15
Gly Thr Arg Ala Glu Val Thr Ser Asp Gln Val Ala Asn Val Val Trp20 25 30Asp Tyr Phe Thr Gln Leu Ser Asn Asn Ala Lys Glu Ala Val Glu Gln35 40 45Phe Gln Lys Thr Asp Val Thr Gln Gln Leu Ser Thr Leu Phe Gln Asp50 55 60Lys Leu Gly Asp Ala Ser Thr Tyr Ala Asp Gly Val His Asn Lys Leu65 70 75 80Val Pro Phe Val Val Gln Leu Asp Leu Arg Asp Arg Met Met Pro His85 90 95Ala Asn Lys Val Thr Gln Thr Phe Gly Glu Asn Met Gln Lys Leu Gln100 105 110Glu His Leu Lys Pro Tyr Ala Val Asp Leu Gln Asp Gln Ile Asn Thr115 120 125Gln Thr Gln Glu Met Lys Leu Gln Leu Thr Pro Tyr Ile Gln Arg Met130 135 140Gln Thr Thr Ile Lys Glu Asn Val Asp Asn Leu His Thr Ser Met Met145 150 155 160Pro Leu Ala Thr Asn Leu Lys Asp Lys Phe Asn Arg Asn Met Glu Glu165 170 175Leu Lys Gly His Leu Thr Pro Arg Ala Asn Glu Leu Lys Ala Thr Ile180 185 190Asp Gln Asn Leu Glu Asp Leu Arg Arg Ser Leu Ala Pro Leu Thr Val195 200 205Gly Val Gln Glu Lys Leu Asn His Gln Met Glu Gly Leu Ala Phe Gln210 215 220Met Lys Lys Asn Ala Glu Glu Leu Gln Thr Lys Val Ser Ala Lys Ile225 230 235 240Asp Gln Leu Gln Lys Asn Leu Ala Pro Leu Val Glu Asp Val Gln Ser245 250 255
Lys Val Lys Gly Asn Thr Glu Gly Leu Gln Lys Ser Leu Glu Asp Leu260 265 270Asn Arg Gln Leu Glu Gln Gln Val Glu Glu Phe Arg Arg Thr Val Glu275 280 285Pro Met Gly Glu Met Phe Asn Lys Ala Leu Val Gln Gln Leu Glu Gln290 295 300Phe Arg Gln Gln Leu Gly Pro Asn Ser Gly Glu Val Glu Ser His Leu305 310 315 320Ser Phe Leu Glu Lys Ser Leu Arg Glu Lys Val Asn Ser Phe Met Ser325 330 335Thr Leu Glu Lys Lys Gly Ser Pro Asp Gln Pro Gln Ala Leu Pro Leu340 345 350Pro Glu Gln Ala Gln Glu Gln Ala Gln Glu Gln Ala Gln Glu Gln Val355 360 365Gln Pro Lys Pro Leu Glu Ser370 375<210>27<211>435<212>PRT<213>Mus musculus castaneus<400>27Met Phe Leu Lys Ala Ala Val Leu Thr Leu Ala Leu Val Ala Ile Thr1 5 10 15Gly Thr Arg Ala Lys Val Thr Ser Asp Gln Val Ala Asn Val Val Trp20 25 30Asp Tyr Phe Thr His Leu Ser Asn Asn Ala Lys Glu Ala Ala Glu Gln35 40 45Phe Gln Lys Thr Asp Val Thr Gln Gln Leu Ser Thr Leu Phe Gln Asp50 55 60Lys Leu Gly Asp Ala Ser Thr Tyr Ala Asp Gly Val Arg Asn Lys Leu65 70 75 80
Val Pro Phe Val Val Gln Leu Ser Gly His Leu Ala Lys Glu Thr Glu85 90 95Arg Val Lys Glu Glu Ile Lys Lys Glu Leu Glu Asp Leu Arg Asp Arg100 105 110Met Met Pro His Ala Asn Lys Val Thr Gln Thr Phe Gly Glu Asn Met115 120 125Gln Lys Leu Gln Glu His Leu Lys Pro Tyr Ala Val Asp Leu Gln Asp130 135 140Gln Ile Asn Thr Gln Thr Gln Glu Met Lys Leu Gln Leu Thr Pro Tyr145 150 155 160Ile Gln Arg Met Gln Thr Thr Ile Lys Glu Asn Val Asp Asn Leu His165 170 175Thr Ser Met Met Pro Leu Ala Thr Asn Leu Lys Asp Lys Phe Asn Arg180 185 190Asn Met Glu Glu Leu Lys Gly His Leu Thr Pro Arg Ala Asn Glu Leu195 200 205Lys Ala Thr Ile Asp Gln Asn Leu Glu Asp Leu Arg Arg Ser Leu Ala210 215 220Pro Leu Thr Val Gly Val Gln Glu Lys Leu Asn His Gln Met Glu Gly225 230 235 240Leu Ala Phe Gln Met Lys Lys Asn Ala Glu Glu Leu Gln Thr Lys Val245 250 255Ser Ala Lys Ile Asp Gln Leu Gln Lys Asn Leu Ala Pro Leu Val Glu260 265 270Asp Val Gln Ser Lys Val Lys Gly Asn Thr Glu Gly Leu Gln Lys Ser275 280 285Leu Lys Asp Leu Asn Arg Gln Leu Glu Gln Gln Val Glu Glu Phe Arg290 295 300Arg Thr Val Glu Pro Met Gly Glu Met Phe Asn Lys Ala Leu Val Gln305 310 315 320
Gln Leu Glu Gln Phe Arg Gln Gln Leu Gly Pro Asn Ser Gly Glu Val325 330 335Glu Ser His Leu Ser Phe Leu Glu Lys Ser Leu Arg Glu Lys Val Asn340 345 350Ser Phe Met Ser Thr Leu Glu Lys Lys Gly Ser Pro Asp Gln Pro Gln355 360 365Ala Leu Pro Leu Pro Glu Gln Ala Gln Glu Gln Ala Gln Glu Gln Ala370 375 380Gln Glu Gln Ala Gln Glu Gln Val Gln Pro Lys Pro Leu Glu Ser Gly385 390 395 400Ala Pro Glu Leu Ser Leu Ser Pro Ser Gln Gln Gln Thr Pro Val Leu405 410 415Pro His His Leu Ser Val Thr Leu Ser Pro Gly Thr Ser Trp Thr His420 425 430Val Pro Thr435<210>28<211>382<212>PRT<213>Sus scrofa<400>28Met Phe Leu Lys Ala Val Val Leu Ser Leu Ala Leu Val Ala Val Thr1 5 10 15Gly Ala Arg Ala Glu Val Asn Ala Asp Gln Val Ala Thr Val Met Trp20 25 30Asp Tyr Phe Ser Gln Leu Gly Ser Asn Ala Lys Lys Ala Val Glu His35 40 45Leu Gln Lys Ser Glu Leu Thr Gln Gln Leu Asn Thr Leu Phe Gln Asp50 55 60Lys Leu Gly Glu Val Asn Thr Tyr Thr Glu Asp Leu Gln Lys Lys Leu65 70 75 80
Val Pro Phe Ala Thr Glu Leu His Glu Arg Leu Thr Lys Asp Ser Glu85 90 95Lys Leu Lys Glu Glu Ile Arg Arg Glu Leu Glu Glu Leu Arg Ala Arg100 105 110Leu Leu Pro His Ala Thr Glu Val Ser Gln Lys Ile Gly Asp Asn Val115 120 125Arg Glu Leu Gln Gln Arg Leu Gly Pro Phe Thr Gly Gly Leu Arg Thr130 135 140Gln Val Asn Thr Gln Val Gln Gln Leu Gln Arg Gln Leu Lys Pro Tyr145 150 155 160Ala Glu Arg Met Glu Ser Val Leu Arg Gln Asn Ile Arg Asn Leu Glu165 170 175Ala Ser Val Ala Pro Tyr Ala Asp Glu Phe Lys Ala Lys Ile Asp Gln180 185 190Asn Val Glu Glu Leu Lys Gly Ser Leu Thr Pro Tyr Ala Glu Glu Leu195 200 205Lys Ala Lys Ile Asp Gln Asn Val Glu Glu Leu Arg Arg Ser Leu Ala210 215 220Pro Tyr Ala Gln Asp Val Gln Glu Lys Leu Asn His Gln Leu Glu Gly225 230 235 240Leu Ala Phe Gln Met Lys Lys Gln Ala Glu Glu Leu Lys Ala Lys Ile245 250 255Ser Ala Asn Ala Asp Glu Leu Arg Gln Lys Leu Val Pro Val Ala Glu260 265 270Asn Val His Gly His Leu Lys Gly Asn Thr Glu Gly Leu Gln Lys Ser275 280 285Leu Leu Glu Leu Arg Ser His Leu Asp Gln Gln Val Glu Glu Phe Arg290 295 300Leu Lys Val Glu Pro Tyr Gly Glu Thr Phe Asn Lys Ala Leu Val Gln
305 310 315 320Gln Val Glu Asp Leu Arg Gln Lys Leu Gly Pro Leu Ala Gly Asp Val325 330 335Glu Gly His Leu Ser Phe Leu Glu Lys Asp Leu Arg Asp Lys Val Asn340 345 350Thr Phe Phe Ser Thr Leu Lys Glu Glu Ala Ser Gln Gly Gln Ser Gln355 360 365Ala Leu Pro Ala Gln Glu Lys Ala Gln Ala Pro Leu Glu Gly370 375 380<210>29<211>401<212>PRT<213>Papio anubis<400>29Gly Ala Arg Ala Glu Val Ser Ala Asp Gln Val Ala Thr Val Met Trp1 5 10 15Asp Tyr Phe Ser Gln Leu Ser Ser Asn Ala Lys Glu Ala Val Glu His20 25 30Leu Gln Lys Ser Glu Leu Thr Gln Gln Leu Asn Ala Leu Phe Gln Asp35 40 45Lys Leu Gly Glu Val Asn Thr Tyr Ala Gly Asp Leu Gln Lys Lys Leu50 55 60Val Pro Phe Ala Thr Glu Leu His Glu Arg Leu Ala Lys Asp Ser Lys65 70 75 80Lys Leu Lys Glu Glu Ile Arg Lys Glu Leu Glu Glu Val Arg Ala Arg85 90 95Leu Leu Pro His Ala Asn Glu Val Ser Gln Lys Ile Gly Glu Asn Val100 105 110Arg Glu Leu Gln Gln Arg Leu Glu Pro Tyr Thr Asp Gln Leu Arg Thr115 120 125Gln Val Asn Thr Gln Thr Glu Gln Leu Arg Arg Gln Leu Thr Pro Tyr
130 135 140Ala Gln Arg Met Glu Arg Val Leu Arg Glu Asn Ala Asp Ser Leu Gln145 150 155 160Thr Ser Leu Arg Pro His Ala Asp Gln Leu Lys Ala Lys Ile Asp Gln165 170 175Asn Val Glu Glu Leu Lys Gly Arg Leu Thr Pro Tyr Ala Asp Glu Phe180 185 190Lys Val Lys Ile Asp Gln Thr Val Glu Glu Leu Arg Arg Ser Leu Ala195 200 205Pro Tyr Ala Gln Asp Ala Gln Glu Lys Leu Asn His Gln Leu Glu Gly210 215 220Leu Ala Phe Gln Met Lys Lys Asn Ala Glu Glu Leu Lys Ala Arg Ile225 230 235 240Ser Ala Ser Ala Glu Glu Leu Arg Gln Arg Leu Ala Pro Leu Ala Glu245 250 255Asp Met Arg Gly Asn Leu Arg Gly Asn Thr Glu Gly Leu Gln Lys Ser260 265 270Leu Ala Glu Leu Gly Gly His Leu Asp Arg His Val Glu Glu Phe Arg275 280 285Leu Arg Val Glu Pro Tyr Gly Glu Asn Phe Asn Lys Ala Leu Val Gln290 295 300Gln Met Glu Gln Leu Arg Gln Lys Leu Gly Pro His Ala Gly Asp Val305 310 315 320Glu Gly His Leu Ser Phe Leu Glu Lys Asp Leu Arg Asp Lys Val Asn325 330 335Ser Phe Phe Ser Thr Phe Lys Glu Lys Glu Ser Gln Asp Asn Thr Leu340 345 350Ser Leu Pro Glu Pro Glu Gln Gln Gln Glu Gln Gln Gln Glu Gln Glu355 360 365
Gln Gln Gln Glu Gln Gln Glu Glu Gln Gln Gln Gln Glu Gln Gln Gln370 375 380Glu Gln Glu Gln Gln Gln Glu Gln Val Gln Met Leu Ala Pro Leu Glu385 390 395 400Ser<210>30<211>429<212>PRT<213>Macaca fascicularis<400>30Met Phe Leu Lys Ala Val Val Leu Thr Leu Ala Leu Val Ala Val Thr1 5 10 15Gly Ala Arg Ala Glu Val Ser Ala Asp Gln Val Ala Thr Val Met Trp20 25 30Asp Tyr Phe Ser Gln Leu Ser Ser Asn Ala Lys Glu Ala Val Glu His35 40 45Leu Gln Lys Ser Glu Leu Thr Gln Gln Leu Asn Ala Leu Phe Gln Asp50 55 60Lys Leu Gly Glu Val Asn Thr Tyr Ala Gly Asp Leu Gln Lys Lys Leu65 70 75 80Val Pro Phe Ala Thr Glu Leu His Glu Arg Leu Ala Lys Asp Ser Glu85 90 95Lys Leu Lys Glu Glu Ile Arg Lys Glu Leu Glu Glu Val Arg Ala Arg100 105 110Leu Leu Pro His Ala Asn Glu Val Ser Gln Lys Ile Gly Glu Asn Val115 120 125Arg Glu Leu Gln Gln Arg Leu Glu Pro Tyr Thr Asp Gln Leu Arg Thr130 135 140Gln Val Asn Thr Gln Thr Glu Gln Leu Arg Arg Gln Leu Thr Pro Tyr145 150 155 160
Ala Gln Arg Met Glu Arg Val Leu Arg Glu Asn Ala Asp Ser Leu Gln165 170 175Thr Ser Leu Arg Pro His Ala Asp Gln Leu Lys Ala Lys Ile Asp Gln180 185 190Asn Val Glu Glu Leu Lys Glu Arg Leu Thr Pro Tyr Ala Asp Glu Phe195 200 205Lys Val Lys Ile Asp Gln Thr Val Glu Glu Leu Arg Arg Ser Leu Ala210 215 220Pro Tyr Ala Gln Asp Ala Gln Glu Lys Leu Asn His Gln Leu Glu Gly225 230 235 240Leu Ala Phe Gln Met Lys Lys Asn Ala Glu Glu Leu Lys Ala Arg Ile245 250 255Ser Ala Ser Ala Glu Glu Leu Arg Gln Arg Leu Ala Pro Leu Ala Glu260 265 270Asp Met Arg Gly Asn Leu Arg Gly Asn Thr Glu Gly Leu Gln Lys Ser275 280 285Leu Ala Glu Leu Gly Gly His Leu Asp Arg His Val Glu Glu Phe Arg290 295 300Leu Arg Val Glu Pro Tyr Gly Glu Asn Phe Asn Lys Ala Leu Val Gln305 310 315 320Gln Met Glu Gln Leu Arg Gln Lys Leu Gly Pro His Ala Gly Asp Val325 330 335Glu Gly His Leu Ser Phe Leu Glu Lys Asp Leu Arg Asp Lys Val Asn340 345 350Ser Phe Phe Ser Thr Phe Lys Glu Lys Glu Ser Gln Asp Asn Thr Leu355 360 365Ser Leu Pro Glu Pro Glu Gln Gln Arg Glu Gln Gln Gln Glu Gln Gln370 375 380Gln Glu Gln Glu Gln Glu Gln Gln Gln Gln Gln Glu Gln Gln Gln Gln385 390 395 400
Gln Glu Gln Gln Arg Glu Gln Gln Gln Gln Glu Gln Gln Gln Glu Gln405 410 415Gln Gln Glu Gln Val Gln Met Leu Ala Pro Leu Glu Ser420 425<210>31<211>91<212>PRT<213>Pan troglodytes<400>31Arg Val Glu Pro Tyr Gly Glu Asn Phe Asn Lys Ala Leu Val Gln Gln1 5 10 15Met Glu Gln Leu Arg Thr Lys Leu Gly Pro His Ala Gly Asp Val Glu20 25 30Gly His Leu Ser Phe Leu Glu Lys Asp Leu Arg Asp Lys Val Asn Ser35 40 45Phe Phe Ser Thr Phe Lys Glu Lys Glu Ser Gln Asp Lys Thr Leu Ser50 55 60Leu Pro Glu Leu Glu Gln Gln Gln Glu Gln Gln Gln Glu Gln Gln Gln65 70 75 80Glu Gln Val Gln Met Leu Ala Pro Leu Glu Ser85 90<210>32<211>401<212>PRT<213>Papio sp<400>32Gly Ala Arg Ala Glu Val Ser Ala Asp Gln Val Ala Thr Val Met Trp1 5 10 15Asp Tyr Phe Ser Gln Leu Ser Ser Asn Ala Lys Glu Ala Val Glu His20 25 30Leu Gln Lys Ser Glu Leu Thr Gln Gln Leu Asn Ala Leu Phe Gln Asp35 40 45
Lys Leu Gly Glu Val Asn Thr Tyr Ala Gly Asp Leu Gln Lys Lys Leu50 55 60Val Pro Phe Ala Thr Glu Leu His Glu Arg Leu Ala Lys Asp Ser Lys65 70 75 80Lys Leu Lys Glu Glu Ile Arg Lys Glu Leu Glu Glu Val Arg Ala Arg85 90 95Leu Leu Pro His Ala Asn Glu Val Ser Gln Lys Ile Gly Glu Asn Val100 105 110Arg Glu Leu Gln Gln Arg Leu Glu Pro Tyr Thr Asp Gln Leu Arg Thr115 120 125Gln Val Asn Thr Gln Thr Glu Gln Leu Arg Arg Gln Leu Thr Pro Tyr130 135 140Ala Gln Arg Met Glu Arg Val Leu Arg Glu Asn Ala Asp Ser Leu Gln145 150 155 160Thr Ser Leu Arg Pro His Ala Asp Gln Leu Lys Ala Lys Ile Asp Gln165 170 175Asn Val Glu Glu Leu Lys Gly Arg Leu Thr Pro Tyr Ala Asp Glu Phe180 185 190Lys Val Lys Ile Asp Gln Thr Val Glu Glu Leu Arg Arg Ser Leu Ala195 200 205Pro Tyr Ala Gln Asp Ala Gln Glu Lys Leu Asn His Gln Leu Glu Gly210 215 220Leu Ala Phe Gln Met Lys Lys Asn Ala Glu Glu Leu Lys Ala Arg Ile225 230 235 240Ser Ala Ser Ala Glu Glu Leu Arg Gln Arg Leu Ala Pro Leu Ala Glu245 250 255Asp Met Arg Gly Asn Leu Arg Gly Asn Thr Glu Gly Leu Gln Lys Ser260 265 270Leu Ala Glu Leu Gly Gly His Leu Asp Arg His Val Glu Glu Phe Arg275 280 285
Leu Arg Val Glu Pro Tyr Gly Glu Asn Phe Asn Lys Ala Leu Val Gln290 295 300Gln Met Glu Gln Leu Arg Gln Lys Leu Gly Pro His Ala Gly Asp Val305 310 315 320Glu Gly His Leu Ser Phe Leu Glu Lys Asp Leu Arg Asp Lys Val Asn325 330 335Ser Phe Phe Ser Thr Phe Lys Glu Lys Glu Ser Gln Asp Asn Thr Leu340 345 350Ser Leu Pro Glu Pro Glu Gln Gln Gln Glu Gln Gln Gln Glu Gln Glu355 360 365Gln Gln Gln Glu Gln Gln Glu Glu Gln Gln Gln Gln Glu Gln Gln Gln370 375 380Glu Gln Glu Gln Gln Gln Glu Gln Val Gln Met Leu Ala Pro Leu Glu385 390 395 400Ser<210>33<211>167<212>PRT<213>Gillichthys mirabilis<400>33Met Lys Phe Leu Val Ala Leu Ala Leu Ile Ser Val Cys Asn Ala Asn1 5 10 15Val Val Trp His Glu Gln Pro Lys Thr Leu Asp Leu Val Arg Asp Thr20 25 30Phe Trp Asp Tyr Val Ala Lys Ala Thr Gln Met Ala Glu Gly Ser Lys35 40 45Gln Ile Gln Asp Ser Glu Leu Gly Gln Glu Val Asn Thr Lys Leu Ser50 55 60Gln Ser Ala Asn Thr Val Gln Tyr Val Val Ala Leu Lys Thr Gln Ala65 70 75 80
Gly Pro Leu Ser Gln Asp Leu Leu Thr Gln Ile Thr Gln Gln Thr Glu85 90 95Thr Leu Lys Ser Arg Leu Glu Thr Glu Leu Ser Ala Val Asn Ala Asn100 105 110Leu Gln Pro Tyr Ala Glu Gln Leu Val Ala Asp Leu Gln Thr Lys Met115 120 125Asp Ala Leu Lys Asp Val Ala Pro Leu Ala Glu Ala Met Asp Pro Glu130 135 140Thr Leu Lys Thr Val Met Gln Thr Arg Thr Glu Asp Ser Ser Lys Leu145 150 155 160Arg Trp Gly Arg Thr Pro Thr165<210>34<211>15<212>PRT<213>Oryctolagus cuniculus<400>34Glu Val Ser Ala Asp Gln Val Ala Thr Val Met Trp Asp Tyr Phe1 5 10 15<210>35<211>312<212>PRT<213>Rattus norvegicus<400>35Met Lys Ala Leu Trp Ala Leu Leu Leu Val Pro Leu Leu Thr Gly Cys1 5 10 15Leu Ala Glu Gly Glu Leu Glu Val Thr Asp Gln Leu Pro Gly Gln Ser20 25 30Asp Gln Pro Trp Glu Gln Ala Leu Asn Arg Phe Trp Asp Tyr Leu Arg35 40 45Trp Val Gln Thr Leu Ser Asp Gln Val Gln Glu Glu Leu Gln Ser Ser50 55 60
Gln Val Thr Gln Glu Leu Thr Val Leu Met Glu Asp Thr Met Thr Glu65 70 75 80Val Lys Ala Tyr Lys Lys Glu Leu Glu Glu Gln Leu Gly Pro Val Ala85 90 95Glu Glu Thr Arg Ala Arg Leu Ala Lys Glu Val Gln Ala Ala Gln Ala100 105 110Arg Leu Gly Ala Asp Met Glu Asp Leu Arg Asn Arg Leu Gly Gln Tyr115 120 125Arg Asn Glu Val Asn Thr Met Leu Gly Gln Ser Thr Glu Glu Leu Arg130 135 140Ser Arg Leu Ser Thr His Leu Arg Lys Met Arg Lys Arg Leu Met Arg145 150 155 160Asp Ala Asp Asp Leu Gln Lys Arg Leu Ala Val Tyr Lys Ala Gly Ala165 170 175Gln Glu Gly Ala Glu Arg Gly Val Ser Ala Ile Arg Glu Arg Leu Gly180 185 190Pro Leu Val Glu Gln Gly Arg Gln Arg Thr Ala Asn Leu Gly Ala Gly195 200 205Ala Ala Gln Pro Leu Arg Asp Arg Ala Gln Ala Leu Ser Asp Arg Ile210 215 220Arg Gly Arg Leu Glu Glu Val Gly Asn Gln Ala Arg Asp Arg Leu Glu225 230 235 240Glu Val Arg Glu Gln Met Glu Glu Val Arg Ser Lys Met Glu Glu Gln245 250 255Thr Gln Gln Ile Arg Leu Gln Ala Glu Ile Phe Gln Ala Arg Ile Lys260 265 270Gly Trp Phe Glu Pro Leu Val Glu Asp Met Gln Arg Gln Trp Ala Asn275 280 285Leu Met Glu Lys Ile Gln Ala Ser Val Ala Thr Asn Ser Ile Ala Ser290 295 300
Thr Thr Val Pro Leu Glu Asn Gln305 310<210>36<211>281<212>PRT<213>Danio rerio<400>36Met Arg Ser Leu Val Val Phe Phe Ala Leu Ala Val Leu Thr Gly Cys1 5 10 15Gln Ala Arg Ser Leu Phe Gln Ala Asp Ala Pro Gln Pro Arg Trp Glu20 25 30Glu Met Val Asp Arg Phe Trp Gln Tyr Val Ser Glu Leu Asn Thr Gln35 40 45Thr Asp Gly Met Val Gln Asn Ile Lys Gly Ser Gln Leu Ser Arg Glu50 55 60Leu Asp Thr Leu Ile Thr Asp Thr Met Ala Glu Leu Ser Ser Tyr Ser65 70 75 80Glu Asn Leu Gln Thr Gln Met Thr Pro Tyr Ala Ser Asp Ala Ala Gly85 90 95Gln Leu Ser Lys Asp Leu Gln Leu Leu Ala Gly Lys Leu Gln Thr Asp100 105 110Met Thr Asp Ala Lys Glu Arg Ser Thr Gln Tyr Leu Gln Glu Leu Lys115 120 125Thr Met Met Glu Gln Asn Ala Asp Asp Val Lys Asn Arg Val Gly Thr130 135 140Tyr Thr Arg Lys Leu Lys Lys Arg Leu Asn Lys Asp Thr Glu Glu Ile145 150 155 160Arg Asn Thr Val Ala Thr Tyr Met Ser Glu Met Gln Ser Arg Ala Ser165 170 175Gln Asn Ala Asp Ala Val Lys Asp Arg Phe Gln Pro Tyr Met Ser Gln180 185 190
Ala Gln Asp Gly Ala Thr Gln Lys Leu Gly Ala Ile Ser Glu Leu Met195 200 205Lys Ala Gln Ala Gln Glu Val Ser Glu Gln Leu Glu Val Gln Ala Gly210 215 220Ala Leu Lys Glu Lys Leu Glu Glu Thr Ala Glu Asn Leu Arg Thr Ser225 230 235 240Leu Glu Gly Arg Val Asp Glu Leu Thr Ser Leu Leu Ala Pro Tyr Ser245 250 255Gln Lys Ile Arg Glu Gln Leu Gln Glu Val Met Asp Lys Ile Lys Glu260 265 270Ala Thr Ala Ala Leu Pro Thr Gln Ala275 280<210>37<211>316<212>PRT<213>Bos taurus<400>37Met Lys Val Leu Trp Val Ala Val Val Val Ala Leu Leu Ala Gly Cys1 5 10 15Gln Ala Asp Met Glu Gly Glu Leu Gly Pro Glu Glu Pro Leu Thr Thr20 25 30Gln Gln Pro Arg Gly Lys Asp Ser Gln Pro Trp Glu Gln Ala Leu Gly35 40 45Arg Phe Trp Asp Tyr Leu Arg Trp Val Gln Thr Leu Ser Asp Gln Val50 55 60Gln Glu Glu Leu Leu Asn Thr Gln Val Ile Gln Glu Leu Thr Ala Leu65 70 75 80Met Glu Glu Thr Met Lys Glu Val Lys Ala Tyr Lys Glu Glu Leu Glu85 90 95Gly Gln Leu Gly Pro Met Ala Gln Glu Thr Gln Ala Arg Val Ser Lys100 105 110
Glu Leu Gln Ala Ala Gln Ala Arg Leu Gly Ser Asp Met Glu Asp Leu115 120 125Arg Asn Arg Leu Ala Gln Tyr Arg Ser Glu Val Gln Ala Met Leu Gly130 135 140Gln Ser Thr Glu Glu Leu Arg Ala Arg Met Ala Ser His Leu Arg Lys145 150 155 160Leu Pro Lys Arg Leu Leu Arg Asp Ala Asp Asp Leu Lys Lys Arg Leu165 170 175Ala Val Tyr Gln Ala Gly Ala Ser Glu Gly Ala Glu Arg Ser Leu Ser180 185 190Ala Ile Arg Glu Arg Phe Gly Pro Leu Val Glu Gln Gly Gln Ser Arg195 200 205Ala Ala Thr Leu Ser Thr Leu Ala Gly Gln Pro Leu Leu Glu Arg Ala210 215 220Glu Ala Trp Arg Gln Lys Leu His Gly Arg Leu Glu Glu Val Gly Val225 230 235 240Arg Ala Gln Asp Arg Leu Asp Lys Ile Arg Gln Gln Leu Glu Glu Val245 250 255His Ala Lys Val Glu Glu Gln Gly Asn Gln Met Arg Leu Gln Ala Glu260 265 270Ala Phe Gln Ala Arg Leu Arg Ser Trp Phe Glu Pro Leu Val Glu Asp275 280 285Met Gln Arg Gln Trp Ala Gly Leu Val Glu Lys Val Gln Leu Ala Leu290 295 300Arg Pro Ser Pro Thr Ser Pro Pro Ser Glu Asn His305 310 315<210>38<211>311<212>PRT<213>Mus musculus<400>38
Met Lys Ala Leu Trp Ala Val Leu Leu Val Thr Leu Leu Thr Gly Cys1 5 10 15Leu Ala Glu Gly Glu Pro Glu Val Thr Asp Gln Leu Glu Trp Gln Ser20 25 30Asn Gln Pro Trp Glu Gln Ala Leu Asn Arg Phe Trp Asp Tyr Leu Arg35 40 45Trp Val Gln Thr Leu Ser Asp Gln Val Gln Glu Glu Leu Gln Ser Ser50 55 60Gln Val Thr Gln Glu Leu Thr Ala Leu Met Glu Asp Thr Met Thr Glu65 70 75 80Val Lys Ala Tyr Lys Lys Glu Leu Glu Glu Gln Leu Gly Pro Val Ala85 90 95Glu Glu Thr Arg Ala Arg Leu Gly Lys Glu Val Gln Ala Ala Gln Ala100 105 110Arg Leu Gly Ala Asp Met Glu Asp Leu Arg Asn Arg Leu Gly Gln Tyr115 120 125Arg Asn Glu Val His Thr Met Leu Gly Gln Ser Thr Glu Glu Ile Arg130 135 140Ala Arg Leu Ser Thr His Leu Arg Lys Met Arg Lys Arg Leu Met Arg145 150 155 160Asp Ala Glu Asp Leu Gln Lys Arg Leu Ala Val Tyr Lys Ala Gly Ala165 170 175Arg Glu Gly Ala Glu Arg Gly Val Ser Ala Ile Arg Glu Arg Leu Gly180 185 190Pro Leu Val Glu Gln Gly Arg Gln Arg Thr Ala Asn Leu Gly Ala Gly195 200 205Ala Ala Gln Pro Leu Arg Asp Arg Ala Gln Ala Phe Gly Asp Arg Ile210 215 220Arg Gly Arg Leu Glu Glu Val Gly Asn Gln Ala Arg Asp Arg Leu Glu225 230 235 240
Glu Val Arg Glu His Met Glu Glu Val Arg Ser Lys Met Glu Glu Gln245 250 255Thr Gln Gln Ile Arg Leu Gln Ala Glu Ile Phe Gln Ala Arg Leu Lys260 265 270Gly Trp Phe Glu Pro Ile Val Glu Asp Met His Arg Gln Trp Ala Asn275 280 285Leu Met Glu Lys Ile Gln Ala Ser Val Ala Thr Asn Pro Ile Ile Thr290 295 300Pro Val Ala Gln Glu Asn Gln305 310<210>39<211>305<212>PRT<213>Canis familiaris<400>39Asp Val Gln Pro Glu Pro Glu Leu Glu Arg Glu Leu Glu Pro Lys Val1 5 10 15Gln Gln Glu Leu Glu Pro Glu Ala Gly Trp Gln Thr Gly Gln Pro Trp20 25 30Glu Ala Ala Leu Ala Arg Phe Trp Asp Tyr Leu Arg Trp Val Gln Thr35 40 45Leu Ser Asp Gln Val Gln Glu Gly Val Leu Asn Thr Gln Val Thr Gln50 55 60Glu Leu Thr Ala Leu Met Asp Glu Thr Met Lys Glu Val Lys Ala Tyr65 70 75 80Lys Ala Glu Leu Asp Glu Gln Leu Gly Pro Met Thr Ser Glu Thr Gln85 90 95Ala Arg Val Ala Lys Glu Leu Gln Ala Ala Gln Ala Arg Leu Arg Ala100 105 110Asp Met Glu Asp Val Arg Asn Arg Leu Thr Gln Tyr Arg Gly Glu Leu115 120 125
Gln Ala Met Leu Gly Gln Ser Ser Glu Glu Leu Arg Ala Arg Phe Ala130 135 140Ser His Met Arg Lys Leu Arg Lys Arg Val Leu Arg Asp Ala Glu Asp145 150 155 160Leu Gln Arg Arg Leu Ala Val Tyr Lys Ala Gly Val Arg Glu Gly Ala165 170 175Glu Arg Ser Val Ser Ser Ile Arg Glu Arg Leu Trp Pro Leu Leu Glu180 185 190Gln Ala Arg Glu Arg Asn Ala Lys Val Gly Ala Leu Ala Thr Gln Pro195 200 205Leu Leu Glu Arg Ala Asp Ala Trp Gly Gln Gln Leu Arg Gly Gln Leu210 215 220Glu Glu Met Ser Ser Arg Ala Arg Gly His Leu Glu Glu Met Arg Glu225 230 235 240Gln Ile Gln Glu Val Arg Val Lys Met Glu Glu Gln Ala Asp Gln Ile245 250 255Arg Gln Lys Ala Glu Ala Phe Gln Ala Arg Leu Lys Ser Trp Phe Glu260 265 270Pro Leu Leu Glu Asp Met Gln Arg Gln Trp Asp Gly Leu Val Glu Lys275 280 285Val Gln Ala Ala Val Ala Thr Ile Pro Thr Ser Lys Pro Val Glu Glu290 295 300Pro305<210>40<211>107<212>PRT<213>Saimiri sciureus<400>40Leu Ser Ser Gln Val Thr Gln Glu Leu Thr Ala Leu Met Asp Glu Thr1 5 10 15
Met Lys Glu Leu Lys Ala Tyr Lys Ser Glu Leu Glu Glu Gln Leu Ser20 25 30Pro Val Ala Glu Glu Thr Arg Ala Arg Leu Ser Lys Glu Leu Gln Ala35 40 45Ala Gln Ala Arg Leu Gly Ala Asp Met Glu Asp Val Arg Ser Arg Leu50 55 60Ala Gln Tyr Arg Ser Glu Val Gln Ala Met Leu Gly Gln Ser Thr Asp65 70 75 80Glu Leu Arg Ala Arg Leu Ala Ser His Leu Arg Lys Leu Arg Lys Arg85 90 95Leu Leu Arg Asp Val Asp Asp Leu Gln Lys Arg100 105<210>41<211>107<212>PRT<213>Macaca mulatta<400>41Leu Ser Pro Gln Val Thr Gln Glu Leu Thr Thr Leu Met Asp Glu Thr1 5 10 15Met Lys Glu Leu Lys Ala Tyr Lys Ser Glu Leu Glu Glu Gln Leu Ser20 25 30Pro Val Ala Glu Glu Thr Arg Ala Arg Leu Ser Lys Glu Leu Gln Ala35 40 45Ala Gln Ala Arg Leu Gly Ala Asp Met Glu Asp Val Arg Ser Arg Leu50 55 60Val Gln Tyr Arg Ser Glu Val Gln Ala Met Leu Gly Gln Ser Thr Glu65 70 75 80Glu Leu Arg Ala Arg Leu Ala Ser His Leu Arg Lys Leu Arg Lys Arg85 90 95Leu Leu Arg Asp Ala Asp Asp Leu Gln Lys Arg100 105
<210>42<211>317<212>PRT<213>Sus scrofa<400>42Met Arg Val Leu Trp Val Ala Leu Val Val Thr Leu Leu Ala Gly Cys1 5 10 15Arg Thr Glu Asp Glu Pro Gly Pro Pro Pro Glu Val His Val Trp Trp20 25 30Glu Glu Ser Lys Trp Gln Gly Ser Gln Pro Trp Glu Gln Ala Leu Gly35 40 45Arg Phe Trp Asp Tyr Leu Arg Trp Val Gln Ser Leu Ser Asp Gln Val50 55 60Gln Glu Glu Leu Leu Ser Thr Lys Val Thr Gln Glu Leu Thr Glu Leu65 70 75 80Ile Glu Glu Ser Met Lys Glu Val Lys Ala Tyr Arg Glu Glu Leu Glu85 90 95Ala Gln Leu Gly Pro Val Thr Gln Glu Thr Gln Ala Arg Leu Ser Lys100 105 110Glu Leu Gln Ala Ala Gln Ala Arg Val Gly Ala Asp Met Glu Asp Val115 120 125Arg Asn Arg Leu Val Leu Tyr Arg Ser Glu Val His Asn Met Leu Gly130 135 140Gln Thr Thr Glu Glu Leu Arg Ser Arg Leu Ala Ser His Leu Arg Asn145 150 155 160Val Arg Lys Arg Leu Val Arg Asp Thr Glu Asp Leu Gln Lys Arg Leu165 170 175Ala Val Tyr Gln Ala Gly Leu Arg Glu Gly Ala Glu Arg Ser Val Ser180 185 190Ala Leu Arg Glu Arg Leu Gly Pro Leu Val Glu Gln Gly Arg Leu Arg195 200 205
Ala Ala Thr Leu Ser Thr Arg Ala Gly Gln Pro Leu Arg Glu Arg Ala210 215 220Glu Ala Trp Gly Gln Lys Leu Arg Gly Arg Leu Glu Glu Met Gly Ser225 230 235 240Arg Thr Arg Asp Arg Leu Asp Glu Met Arg Asp Glu Leu Glu Glu Val245 250 255Arg Thr Lys Val Glu Glu Gln Gly Ser Gln Leu Arg Leu Gln Ala Glu260 265 270Ala Phe Gln Ala Arg Leu Lys Gly Trp Phe Glu Pro Leu Val Glu Asp275 280 285Met Arg Arg Gln Trp Ala Gly Leu Val Glu Arg Met Gln Ser Ala Val290 295 300Ser Ile Ser Ser Ser Thr Ser Ala Pro Ser Asp Asn Gln305 310 315<210>43<211>311<212>PRT<213>Oryctolagus cuniculus<400>43Met Lys Val Trp Trp Ala Val Leu Ala Ala Ala Ile Leu Ala Gly Cys1 5 10 15Arg Ala Gln Thr Glu Gln Glu Val Glu Val Pro Glu Gln Ala Arg Trp20 25 30Lys Ala Gly Gln Pro Trp Glu Leu Ala Leu Gly Arg Phe Trp Asp Tyr35 40 45Leu Arg Trp Val Gln Ser Leu Ser Asp Gln Val Gln Glu Glu Leu Leu50 55 60Ser Ser Gln Val Thr Gln Glu Leu Thr Met Leu Met Glu Glu Thr Met65 70 75 80Lys Glu Val Lys Ala Tyr Lys Ser Glu Leu Glu Glu Gln Leu Ser Pro85 90 95
Met Ala Gln Glu His Arg Ala Arg Leu Ser Lys Glu Leu Gln Val Ala100 105 110Gly Ala Leu Glu Ala Asp Met Glu Asp Val Cys Asn Arg Leu Ala Gln115 120 125Tyr Arg Gly Glu Ala Gln Ala Met Leu Gly Gln Ser Thr Glu Glu Leu130 135 140Ala Arg Ala Phe Ser Ser His Leu Arg Lys Leu Arg Lys Arg Leu Leu145 150 155 160Arg Asp Ala Glu Asp Leu Gln Lys Arg Met Ala Val Tyr Gly Ala Gly165 170 175Ala Arg Glu Gly Ala Glu Arg Gly Val Ser Ala Val Arg Glu Arg Leu180 185 190Gly Ser Arg Leu Glu Arg Gly Arg Leu Arg Val Ala Thr Val Gly Thr195 200 205Leu Ala Gly Arg Pro Leu Arg Glu Arg Ala Gln Ala Trp Gly Glu Arg210 215 220Leu Arg Gly His Leu Glu Glu Val Gly Ser Arg Ala Arg Asp Arg Leu225 230 235 240Asn Glu Val Arg Glu Gln Val Glu Glu Val Arg Val Lys Val Glu Glu245 250 255Gln Ala Pro Gln Met Arg Leu Gln Ala Glu Ala Phe Gln Ala Arg Leu260 265 270Lys Ser Trp Phe Glu Pro Leu Val Glu Asp Met Gln Arg Gln Trp Ala275 280 285Gly Leu Val Glu Lys Leu Gln Ala Ala Met Pro Ser Lys Ala Pro Ala290 295 300Ala Ala Pro Ile Glu Asn Gln305 310<210>44
<211>317<212>PRT<213>Papio anubis<400>44Met Lys Val Leu Trp Ala Ala Leu Leu Val Thr Phe Leu Ala Gly Cys1 5 10 15Gln Ala Lys Val Glu Gln Pro Val Glu Pro Glu Thr Glu Pro Asp Val20 25 30Arg Gln Gln Ala Glu Trp Gln Ser Gly Gln Pro Trp Glu Leu Ala Leu35 40 45Gly Arg Phe Trp Asp Tyr Leu Arg Trp Val Gln Thr Leu Ser Glu Gln50 55 60Val Gln Glu Glu Leu Leu Ser Pro Gln Val Thr Gln Glu Leu Thr Thr65 70 75 80Leu Met Asp Glu Thr Met Lys Glu Leu Lys Ala Tyr Lys Ser Glu Leu85 90 95Glu Glu Gln Leu Ser Pro Val Ala Glu Glu Thr Arg Ala Arg Leu Ser100 105 110Lys Glu Leu Gln Ala Ala Gln Ala Arg Leu Gly Ala Asp Met Glu Asp115 120 125Val Arg Ser Arg Leu Val Gln Tyr Arg Ser Glu Val Gln Ala Met Leu130 135 140Gly Gln Ser Thr Glu Glu Leu Arg Ala Arg Leu Ala Ser His Leu Arg145 150 155 160Lys Leu Arg Lys Arg Leu Leu Arg Asp Ala Asp Asp Leu Gln Lys Arg165 170 175Leu Ala Val Tyr Gln Ala Gly Ala Arg Glu Gly Ala Glu Arg Gly Val180 185 190Ser Ala Ile Arg Glu Arg Leu Gly Pro Leu Val Glu Gln Gly Arg Val195 200 205Arg Ala Ala Thr Val Gly Ser Leu Ala Ser Gln Pro Leu Gln Glu Arg
210 215 220Ala Gln Ala Leu Gly Glu Arg Leu Arg Ala Arg Met Glu Glu Met Gly225 230 235 240Ser Arg Thr Arg Asp Arg Leu Asp Glu Val Lys Glu Gln Val Ala Glu245 250 255Val Arg Ala Lys Leu Glu Glu Gln Ala Gln Gln Ile Ser Leu Gln Ala260 265 270Glu Ala Phe Gln Ala Arg Leu Lys Ser Trp Phe Glu Pro Leu Val Glu275 280 285Asp Met Gln Arg Gln Trp Ala Gly Leu Val Glu Lys Val Gln Ala Ala290 295 300Val Gly Ala Ser Thr Ala Pro Val Pro Ser Asp Asn His305 310 315<210>45<211>317<212>PRT<213>Macaca fascicularis<400>45Met Lys Val Leu Trp Ala Ala Leu Leu Val Thr Phe Leu Ala Gly Cys1 5 10 15Gln Ala Lys Val Glu Gln Pro Val Glu Pro Glu Thr Glu Pro Glu Leu20 25 30Arg Gln Gln Ala Glu Gly Gln Ser Gly Gln Pro Trp Glu Leu Ala Leu35 40 45Gly Arg Phe Trp Asp Tyr Leu Arg Trp Val Gln Thr Leu Ser Glu Gln50 55 60Val Gln Glu Glu Leu Leu Ser Pro Gln Val Thr Gln Glu Leu Thr Thr65 70 75 80Leu Met Asp Glu Thr Met Lys Glu Leu Lys Ala Tyr Lys Ser Glu Leu85 90 95Glu Glu Gln Leu Ser Pro Val Ala Glu Glu Thr Arg Ala Arg Leu Ser
100 105 110Lys Glu Leu Gln Ala Ala Gln Ala Arg Leu Gly Ala Asp Met Glu Asp115 120 125Val Arg Ser Arg Leu Val Gln Tyr Arg Ser Glu Val Gln Ala Met Leu130 135 140Gly Gln Ser Thr Glu Glu Leu Arg Ala Arg Leu Ala Ser His Leu Arg145 150 155 160Lys Leu Arg Lys Arg Leu Leu Arg Asp Ala Asp Asp Leu Gln Lys Arg165 170 175Leu Ala Val Tyr Gln Ala Gly Ala Arg Glu Gly Ala Glu Arg Gly Val180 185 190Ser Ala Ile Arg Glu Arg Leu Gly Pro Leu Val Glu Gln Gly Arg Val195 200 205Arg Ala Ala Thr Val Gly Ser Leu Ala Ser Gln Pro Leu Gln Glu Arg210 215 220Ala Gln Ala Leu Gly Glu Arg Leu Arg Ala Arg Met Glu Glu Met Gly225 230 235 240Ser Arg Thr Arg Asp Arg Leu Asp Glu Val Lys Glu Gln Val Ala Glu245 250 255Val Arg Ala Lys Leu Glu Glu Gln Ala Gln Gln Ile Ser Leu Gln Ala260 265 270Glu Ala Phe Gln Ala Arg Leu Lys Ser Trp Phe Glu Pro Leu Val Glu275 280 285Asp Met Gln Arg Gln Trp Ala Gly Leu Val Glu Lys Val Gln Ala Ala290 295 300Val Gly Ala Ser Thr Ala Pro Val Pro Ile Asp Asn His305 310 315<210>46<211>298<212>PRT<213>Cavia porcellus
<400>46Met Lys Val Leu Trp Ala Ala Leu Val Val Thr Leu Leu Ala Gly Cys1 5 10 15Arg Ala Asp Val Glu Pro Glu Val Glu Val Arg Glu Pro Ala Val Trp20 25 30Gln Ser Gly Gln Pro Trp Glu Leu Ala Leu Ser Arg Phe Trp Asp Tyr35 40 45Leu Arg Trp Val Gln Thr Leu Ser Asp Gln Val Gln Glu Glu Leu Leu50 55 60Ser Asn Gln Val Thr Gln Glu Leu Thr Leu Leu Ile Glu Asp Thr Met65 70 75 80Lys Glu Val Lys Ala Tyr Lys Ala Glu Leu Glu Lys Glu Leu Gly Pro85 90 95Val Ala Glu Asp Thr Lys Ala Arg Leu Ala Lys Glu Leu Gln Ala Ala100 105 110Gln Ala Arg Leu Gly Ala Asp Met Glu Glu Val Arg Asn Arg Leu Ser115 120 125Gln Tyr Arg Ser Glu Val Gln Ala Met Leu Gly Gln Ser Ser Glu Glu130 135 140Leu Arg Ala Arg Leu Thr Ser His Pro Arg Lys Met Lys Arg Arg Leu145 150 155 160Gln Arg Asp Ile Asp Glu Leu Gln Lys Arg Met Ala Val Tyr Lys Ala165 170 175Gly Ala Gln Glu Gly Ala Glu Arg Gly Val Ser Ala Ile Arg Glu Arg180 185 190Leu Gly Ser Leu Ile Glu Gln Gly Arg Leu Gln Ala Leu Ala Ser Gln195 200 205Pro Leu Gln Glu Arg Ala Gln Ala Trp Gly Glu Gln Met Arg Gly Arg210 215 220
Leu Glu Lys Val Gly Ser Gln Ala Arg Asp Arg Leu Glu Glu Val Arg225 230 235 240Glu Gln Met Glu Glu Val Arg Val Lys Val Glu Glu Gln Ala Glu Ala245 250 255Phe Gln Ala Arg Leu Lys Ser Trp Phe Glu Pro Met Met Glu Asp Met260 265 270Arg Arg Gln Trp Ala Glu Leu Ile Gln Lys Val Gln Val Ala Val Gly275 280 285Ala Ser Thr Ser Ala Pro Ser Gln Glu Pro290 295<210>47<211>329<212>PRT<213>Zalophus californianus<400>47Met Lys Val Leu Trp Ala Ala Leu Val Val Ala Leu Leu Ala Gly Cys1 5 10 15Trp Ala Asp Val Glu Pro Glu Ser Pro Leu Glu Glu Asn Leu Glu Pro20 25 30Glu Leu Glu Pro Lys Arg Glu Leu Glu Gln Glu Val Glu Pro Glu Ala35 40 45Gly Trp Gln Ala Gly Gln Pro Trp Glu Leu Ala Leu Ala Arg Phe Trp50 55 60Asp Tyr Leu Arg Trp Val Gln Thr Leu Ser Asp Gln Val Gln Glu Glu65 70 75 80Val Leu Ser Asn Gln Val Thr Gln Glu Leu Thr Thr Leu Met Glu Glu85 90 95Thr Met Lys Glu Ile Lys Ala Tyr Arg Ala Glu Leu Glu Glu Gln Leu100 105 110Gly Pro Met Ala Ser Glu Thr Gln Ala Arg Val Ala Lys Glu Leu Gln115 120 125
Ala Ala Gln Ala Arg Leu Arg Ser Asp Met Glu Asp Val Arg Thr Arg130 135 140Leu Ser Gln Tyr Arg Gly Glu Val Gln Ala Met Leu Gly Gln Ser Thr145 150 155 160Glu Glu Leu Arg Ala Arg Phe Ala Ser His Met Arg Lys Leu Arg Lys165 170 175Arg Val Leu Arg Asp Ala Glu Asp Leu Gln Lys Arg Leu Ala Val Tyr180 185 190Arg Ala Gly Val Arg Glu Gly Ala Glu Arg Ser Val Ser Thr Ile Arg195 200 205Glu Arg Leu Trp Pro Leu Leu Glu Gln Ala Arg Thr Arg His Ala Lys210 215 220Val Asp Ala Leu Ala Thr Gln Pro Leu Arg Glu Arg Val Asn Ala Leu225 230 235 240Gly Gln Gln Leu Arg Gly Arg Leu Glu Glu Val Gly Ser Arg Ala Arg245 250 255Ser His Leu Asp Glu Val Arg Glu Gln Met Glu Glu Val Gln Ala Lys260 265 270Met Glu Glu Gln Ala Asn Gln Met Arg Gln Gln Ala Glu Ala Phe Gln275 280 285Ala Arg Leu Lys Gly Trp Phe Glu Pro Leu Val Glu Asp Met Gln Arg290 295 300Gln Trp Ala Val Leu Val Glu Lys Val Gln Ala Ala Val Gly Thr Ser305 310 315 320Pro Thr Thr Pro Pro Val Glu Thr Lys325<210>48<211>316<212>PRT<213>Ovis sp.
<400>48
Met Lys Val Leu Trp Val Ala Leu Val Val Ala Leu Leu Ala Gly Cys1 5 10 15Gln Ala Asp Met Glu Gly Glu Leu Gly Ser Glu Glu Pro Leu Pro Pro20 25 30Glu Gln Pro Arg Gly Gln Asp Ser Gln Pro Trp Glu Gln Val Leu Gly35 40 45Arg Leu Trp Asp Tyr Leu Arg Trp Val Gln Thr Leu Ser Asp Gln Val50 55 60Gln Glu Glu Leu Leu Asn Thr Gln Val Ile Gln Glu Leu Thr Val Leu65 70 75 80Met Glu Glu Thr Met Lys Glu Val Lys Ala Tyr Arg Glu Glu Leu Glu85 90 95Gly Gln Leu Ala Pro Met Ala Gln Glu Thr Gln Ala Arg Val Ser Lys100 105 110Glu Leu Gln Ala Ala Gln Ala Arg Leu Gly Ser Asp Met Glu Asp Leu115 120 125Arg Asn Arg Leu Ala Gln Tyr Arg Ser Glu Val Gln Ala Met Leu Gly130 135 140Gln Ser Thr Glu Glu Leu Arg Ala Arg Met Ala Ser His Leu Arg Lys145 150 155 160Leu Arg Lys Arg Leu Leu Arg Asp Ala Asp Asp Leu Lys Lys Arg Leu165 170 175Ala Val Tyr Gln Ala Gly Ala Ser Glu Gly Ala Glu Arg Ser Val Ser180 185 190Ala Ile Arg Glu Arg Leu Arg Pro Leu Val Glu Gln Ser Gln Ser Arg195 200 205Ala Ala Thr Leu Ser Thr Gln Val Gly Gln Pro Leu Leu Asp Arg Ala210 215 220Glu Ala Trp Arg Gln Lys Leu His Gly Arg Leu Glu Glu Val Gly Val225 230 235 240
Arg Ala Gln Asp Arg Leu Asp Lys Met Arg Gln Gln Leu Glu Glu Val245 250 255Arg Ser Lys Val Glu Glu Gln Gly Ser Gln Ile Arg Leu Gln Ala Glu260 265 270Ala Phe Gln Ala Arg Leu Arg Ser Trp Phe Glu Pro Leu Val Glu Asp275 280 285Met Gln Arg Gln Trp Ala Gly Leu Val Glu Lys Val Gln Leu Ala Leu290 295 300His Leu Ser Pro Thr Ser Pro Pro Ser Glu Asn His305 310 315<210>49<211>317<212>PRT<213>Pongo pygmaeus<400>49Met Lys Val Leu Trp Ala Ala Leu Leu Val Thr Phe Leu Ala Gly Cys1 5 10 15Gln Ala Lys Val Glu Gln Val Val Glu Thr Glu Pro Glu Pro Glu Leu20 25 30Arg Gln Gln Ala Glu Trp Gln Ser Gly Gln Arg Trp Glu Leu Ala Leu35 40 45Gly Arg Phe Trp Asp Tyr Leu Arg Trp Val Gln Thr Leu Ser Glu Gln50 55 60Val Gln Glu Glu Leu Leu Ser Ser Gln Val Thr Gln Glu Leu Thr Ala65 70 75 80Leu Met Asp Glu Thr Met Lys Glu Leu Lys Ala Tyr Lys Ser Glu Leu85 90 95Glu Glu Gln Leu Thr Pro Val Ala Glu Glu Thr Arg Ala Arg Leu Ser100 105 110Lys Glu Leu Gln Ala Ala Gln Ala Arg Leu Gly Ala Asp Met Glu Asp115 120 125
Val Arg Gly Arg Leu Val Gln Tyr Arg Gly Glu Val Gln Ala Met Leu130 135 140Gly Gln Ser Thr Glu Glu Leu Arg Ala Arg Leu Ala Ser His Leu Arg145 150 155 160Lys Leu Arg Lys Arg Leu Leu Arg Asp Ala Asp Asp Leu Gln Lys Arg165 170 175Leu Ala Val Tyr Gln Ala Gly Ala Arg Glu Gly Ala Glu Arg Gly Val180 185 190Ser Ala Ile Arg Glu Arg Leu Gly Pro Leu Val Glu Gln Gly Arg Val195 200 205Arg Ala Ala Thr Val Gly Ser Val Ala Gly Lys Pro Leu Gln Glu Arg210 215 220Ala Gln Ala Trp Gly Glu Arg Leu Arg Ala Arg Met Glu Glu Met Gly225 230 235 240Ser Arg Thr Arg Asp Arg Leu Asp Glu Val Lys Glu Gln Val Ala Glu245 250 255Val Arg Ala Lys Leu Glu Glu Gln Ala Gln Gln Ile Arg Leu Gln Ala260 265 270Glu Ala Phe Gln Ala Arg Leu Lys Ser Trp Phe Glu Pro Leu Val Glu275 280 285Asp Met Gln Arg Gln Trp Ala Gly Leu Val Glu Lys Val Gln Ala Ala290 295 300Val Gly Thr Ser Ala Ala Pro Val Pro Ser Asp Asn His305 310 315<210>50<211>317<212>PRT<213>Hylobates lar<400>50Met Lys Val Leu Trp Ala Ala Leu Leu Val Thr Phe Leu Ala Gly Cys1 5 10 15
Gln Ala Lys Val Glu Gln Ala Val Glu Pro Glu Pro Glu Pro Glu Leu20 25 30Arg Gln Gln Ala Glu Trp Gln Ser Gly Gln Pro Trp Glu Leu Ala Leu35 40 45Gly Arg Phe Trp Asp Tyr Leu Arg Trp Val Gln Thr Leu Ser Glu Gln50 55 60Val Gln Glu Glu Leu Leu Ser Ser Gln Val Thr Gln Glu Leu Thr Ala65 70 75 80Leu Met Asp Glu Thr Met Lys Glu Leu Lys Ala Tyr Arg Ser Glu Leu85 90 95Glu Glu Gln Leu Thr Pro Val Ala Glu Glu Thr Arg Ala Arg Leu Ser100 105 110Lys Glu Leu Gln Ala Ala Gln Ala Arg Leu Gly Ala Asp Met Glu Asp115 120 125Val Arg Gly Arg Leu Val Gln Tyr Arg Gly Glu Val Gln Ala Met Leu130 135 140Gly Gln Ser Thr Glu Glu Leu Arg Ala Arg Leu Ala Ser His Leu Arg145 150 155 160Lys Leu Arg Lys Arg Leu Leu Arg Asp Ala Asp Asp Leu Gln Lys Arg165 170 175Leu Ala Val Tyr Gln Ala Gly Ala Arg Glu Gly Ala Glu Arg Gly Val180 185 190Ser Ala Ile Arg Glu Arg Leu Gly Pro Leu Val Glu Gln Gly Arg Val195 200 205Arg Ala Ala Thr Val Gly Ser Leu Ala Gly Gln Pro Leu Gln Glu Arg210 215 220Ala Gln Ala Trp Gly Glu Arg Leu Arg Ala Arg Met Glu Glu Val Gly225 230 235 240Gly Arg Thr Arg Asp Arg Leu Asp Glu Val Lys Glu Gln Val Ala Glu245 250 255
Val Arg Ala Lys Leu Glu Glu Gln Ala Gln Gln Ile Arg Leu Gln Ala260 265 270Glu Ala Phe Gln Ala Arg Leu Lys Ser Trp Phe Glu Pro Leu Val Glu275 280 285Asp Met Gln Arg Gln Trp Ala Gly Leu Val Glu Lys Val Gln Ala Ala290 295 300Val Gly Thr Ser Ala Ala Pro Val Pro Ser Asp Asn His305 310 315<210>51<211>317<212>PRT<213>Gorilla gorilla<400>51Met Lys Val Leu Trp Ala Ala Leu Leu Val Thr Phe Leu Ala Gly Cys1 5 10 15Gln Ala Lys Val Glu Gln Ala Val Glu Thr Glu Pro Glu Pro Glu Leu20 25 30His Gln Gln Ala Glu Trp Gln Ser Gly Gln Arg Trp Glu Leu Ala Leu35 40 45Gly Arg Phe Trp Asp Tyr Leu Arg Trp Val Gln Thr Leu Ser Glu Gln50 55 60Val Gln Glu Glu Leu Leu Ser Ser Gln Val Thr Gln Glu Leu Thr Ala65 70 75 80Leu Met Asp Glu Thr Met Lys Glu Leu Lys Ala Tyr Lys Ser Glu Leu85 90 95Glu Glu Gln Leu Thr Pro Val Ala Glu Glu Thr Arg Ala Arg Leu Ser100 105 110Lys Glu Leu Gln Ala Ala Gln Ala Arg Leu Gly Ala Asp Met Glu Asp115 120 125Val Arg Gly Arg Leu Ala Gln Tyr Arg Gly Glu Val Gln Ala Met Leu130 135 140
Gly Gln Ser Thr Glu Glu Leu Arg Ala Arg Leu Ala Ser His Leu Arg145 150 155 160Lys Leu Arg Lys Arg Leu Leu Arg Asp Ala Asp Asp Leu Gln Lys Arg165 170 175Leu Ala Val Tyr Gln Ala Gly Ala Arg Glu Gly Ala Glu Arg Gly Val180 185 190Ser Ala Ile Arg Glu Arg Leu Gly Pro Leu Val Glu Gln Gly Arg Val195 200 205Arg Ala Ala Thr Val Gly Ser Leu Ala Gly Gln Pro Leu Gln Glu Arg210 215 220Ala Gln Ala Trp Gly Glu Arg Leu Arg Ala Arg Met Glu Glu Met Gly225 230 235 240Ser Arg Thr Arg Asp Arg Leu Asp Glu Val Lys Glu Gln Val Ala Glu245 250 255Val Arg Ala Lys Leu Glu Glu Gln Ala Gln Gln Ile Arg Leu Gln Ala260 265 270Glu Ala Phe Gln Ala Arg Leu Lys Ser Trp Phe Glu Pro Leu Val Glu275 280 285Asp Met Gln Arg Gln Trp Ala Gly Leu Val Glu Lys Val Gln Ala Ala290 295 300Met Gly Thr Ser Ala Ala Pro Val Pro Ser Asp Asn His305 310 315<210>52<211>317<212>PRT<213>Pan troglodytes<400>52Met Lys Val Leu Trp Ala Ala Leu Leu Val Thr Phe Leu Ala Gly Cys1 5 10 15Gln Ala Lys Val Glu Gln Val Val Glu Thr Glu Pro Glu Pro Glu Leu20 25 30
His Gln Gln Ala Glu Trp Gln Ser Gly Gln Arg Trp Glu Leu Ala Leu35 40 45Gly His Phe Trp Asp Tyr Leu Arg Trp Val Gln Thr Leu Ser Glu Gln50 55 60Val Gln Glu Glu Leu Leu Ser Ser Gln Val Thr Gln Glu Leu Thr Ala65 70 75 80Leu Met Asp Glu Thr Met Lys Glu Leu Lys Ala Tyr Lys Ser Glu Leu85 90 95Glu Glu Gln Leu Thr Pro Val Ala Glu Glu Thr Arg Ala Arg Leu Ser100 105 110Lys Glu Leu Gln Ala Ala Gln Ala Arg Leu Gly Ala Asp Met Glu Asp115 120 125Val Arg Gly Arg Leu Val Gln Tyr Arg Gly Glu Val Gln Ala Met Leu130 135 140Gly Gln Ser Thr Glu Glu Leu Arg Ala Arg Leu Ala Ser His Leu Arg145 150 155 160Lys Leu Arg Lys Arg Leu Leu Arg Asp Ala Asp Asp Leu Gln Lys Arg165 170 175Leu Ala Val Tyr Gln Ala Gly Ala Arg Glu Gly Ala Glu Arg Gly Val180 185 190Ser Ala Ile Arg Glu Arg Leu Gly Pro Leu Val Glu Gln Gly Arg Val195 200 205Arg Ala Ala Thr Val Gly Ser Leu Ala Gly Gln Pro Leu Gln Glu Arg210 215 220Ala Gln Ala Trp Gly Glu Arg Leu Arg Ala Arg Met Glu Glu Met Gly225 230 235 240Ser Arg Thr Arg Asp Arg Leu Asp Glu Val Lys Glu Gln Val Ala Glu245 250 255Val Arg Ala Lys Leu Glu Glu Gln Ala Gln Gln Ile Arg Lau Gln Ala
260 265 270Glu Ala Phe Gln Ala Arg Leu Lys Ser Trp Phe Glu Pro Leu Val Glu275 280 285Asp Met Gln Arg Gln Trp Ala Gly Leu Val Glu Lys Val Gln Ala Ala290 295 300Met Gly Thr Ser Ala Ala Pro Val Pro Ser Asp Asn His305 310 315<210>53<21l>313<212>PRT<213>Tupaia glis<400>53Met Lys Val Leu Trp Ala Val Leu Ala Phe Ala Phe Leu Thr Gly Cys1 5 10 15Arg Ala Asp Val Glu Pro Gln Leu Glu Pro Glu Val Arg Glu Pro Pro20 25 30Lys Trp Gln Ala Gly Gln Pro Trp Glu Leu Ala Leu Gly Arg Phe Trp35 40 45Asp Tyr Leu Arg Trp Val Gln Thr Leu Ser Asp Gln Val Gln Glu Glu50 55 60Leu Leu Ser Ser Gln Val Thr Gln Glu Leu Thr Val Leu Met Glu Glu65 70 75 80Thr Met Lys Glu Val Lys Ala Tyr Lys Ala Glu Leu Glu Glu Gln Leu85 90 95Gly Pro Met Lys Glu Glu Thr Gln Ala Arg Leu Ser Lys Glu Leu Gln100 105 110Ala Ala Gln Ala Arg Leu Gly Ala Asp Met Glu Asp Val Arg Thr Arg115 120 125Leu Ala Gln Tyr Arg Ser Glu Val His Thr Met Leu Gly Gln Ser Thr130 135 140Glu Glu Leu Arg Ala Arg Leu Ser Ser His Leu Arg Lys Met Arg Lys
145 150 155 160Arg Leu Leu Arg Asp Ala Glu Asp Leu Gln Lys Arg Leu Ala Val Tyr165 170 175Arg Ala Gly Val Gln Glu Gly Ala Glu Arg Gly Val Ser AlaIle Arg180 185 190Glu Arg Leu Gly Pro Leu Met Glu Gln Gly Arg Leu Arg Ala Asn Thr195 200 205Val Ser Ala Leu Ala Val Gln Pro Leu Gln Glu Arg Ala Gln Ala Trp210 215 220Gly Glu Arg Leu Arg Gly Arg Leu Gln Glu Val Gly Ser Gln Ala Arg225 230 235 240Asp Arg Leu Asp Glu Val Arg Glu Gln Val Glu Glu Val Arg Ala Lys245 250 255Val Glu Glu Gln Ala Thr Gln Met Arg Leu Gln Ala Glu Ala Phe Gln260 265 270Ala Arg Leu Gln Ser Trp Phe Glu Pro Leu Val Lys Asp Val Gln Arg275 280 285Gln Trp Ala Glu Leu Val Glu Lys Val Gln Ala Ala Val Gly Thr Ser290 295 300Ala Ala Pro Val Ser Ser Glu Asn His305 310<210>54<211>275<212>PRT<213>Oncorhynchus mykiss<400>54Met Lys Ala Val Ala Ile Ile Leu Ala Leu Ala Val Ile Ser Gly Cys1 5 10 15His Ala Arg Ala Val Arg Gln Ala Glu Ala Leu Pro Asn Leu Trp Glu20 25 30Glu Asn Val Glu Arg Phe Trp Thr Tyr Val Ser Glu Ile Asn Ser Arg
35 40 45Ala Asp Gly Leu Val Glu Asn Leu Lys Ala Ser Gln Leu Ser Arg Glu50 55 60Leu Asp Thr Leu Ile Thr Asp Thr Met Ala Glu Leu Thr Val Tyr Arg65 70 75 80Glu Asp Ile Gln Thr Lys Leu Val Pro Tyr Ala Gln Asp Thr Ala Ala85 90 95Leu Leu Gly Gln Asp Leu Gln Leu Leu Thr Thr Lys Leu Gln Thr Asp100 105 110Met Val Asp Ala Lys Glu Arg Ser Thr Gln Tyr Leu Gly Glu Leu Lys115 120 125Thr Met Met Glu Gln Asn Ala Asp Asp Val His Asn Arg Val Asn Thr130 135 140Tyr Thr Arg Lys Leu Lys Lys Arg Leu Asn Lys Asp Thr Glu Glu Ile145 150 155 160Arg Asn Thr Val Ala Thr Tyr Leu Gly Glu Ile Gln Ser Arg Thr Ser165 170 175Gln Asn Met Asp Leu Val Lys Glu Arg Val Glu Pro Phe Val Ser Gln180 185 190Ala His Asp Thr Ala Ala Gln Arg Leu Gly Ser Phe Thr Asp Leu Leu195 200 205Lys Asn Gln Ala Gln Asp Leu Ser Gln Gln Val Ser Thr Gln Ala Glu210 215 220Gly Met Arg Glu Gln Leu Glu Ala Thr Ala Glu Asp Leu Arg Thr Thr225 230 235 240Leu Glu Gly Lys Ile Asp Glu Leu Ser Ser Leu Ile Ala Pro Tyr Ala245 250 255Ala Lys Ile Arg Glu His Leu Gln Thr Ala Met Asp Lys Val Lys Glu260 265 270
Thr Thr Val275<210>55<211>224<212>PRT<213>Scophthalmus maximus<400>55Leu Glu Asn Leu Lys Ala Ser Gln Leu Ser Arg Glu Leu Asp Thr Leu1 5 10 15Ile Thr Asp Thr Met Ser Glu Leu Ser Ala Tyr Arg Asn Asp Leu Gln20 25 30Thr Lys Ile Ser Pro Tyr Ala Glu Met Ser Thr Gly Gln Leu Thr Gln35 40 45Asp Leu Gln Leu Leu Ala Asn Lys Leu Gln Lys Asp Met Val Asp Ala50 55 60Lys Glu Arg Ser Thr Gln Tyr Leu Gly Glu Leu Lys Thr Met Val Glu65 70 75 80Gln Asn Thr Asp Asp Val Arg Gly Arg Val Thr Thr Tyr Ser Asn Lys85 90 95Leu Lys Lys Arg Leu Asn Lys Asp Thr Glu Glu Ile Arg Asn Thr Val100 105 110Ala Thr Tyr Leu Gly Glu Leu Gln Ser Arg Thr Ser Gln Asn Leu Asp115 120 125Thr Val Ser Glu His Val Gln Pro Tyr Val Gln Gln Ala Ser Asp Ser130 135 140Ala Thr Lys Lys Leu Asn Asp Ile Ser Thr Met Val Gln Asn Leu Ala145 150 155 160Glu Gly Leu Gly Leu Gln Leu Glu Thr Gln Ala Glu Gly Ala Arg Thr165 170 175Gln Leu Glu Ala Thr Ala Lys Glu Leu Phe Thr Ser Leu Glu Gly Lys180 185 190
Ile Asp Glu Leu Ser Ser Leu Phe Ser Pro Tyr Ala Thr Gln Ile Gln195 200 205Glu Gln Val Gly Asn Ile Met Asp Lys Val Lys Glu Thr Thr Ser Ala210 215 220<210>56<211>345<212>DNA<213>Arabidopsis thaliana<400>56atggcttcgg aagaaggaca agtgatcgcc tgccacaccg ttgagacatg gaacgagcag 60cttcagaagg ctaatgaatc caaaactctt gtggtggttg atttcacggc ttcttggtgt120ggaccatgtc gtttcatcgc tccattcttt gctgatttgg ctaagaaact tcctaacgtg180cttttcctca aggttgatac tgatgaattg aagtcggtgg caagtgattg ggcgatacag240gcgatgccaa ccttcatgtt tttgaaggaa gggaagattt tggacaaagt tgttggagcc300aagaaagatg agcttcagtc taccattgcc aaacacttgg cttaa345<210>57<211>743<212>DNA<213>Artificial Sequence<220>
<223>soluble GFP<400>57ggatccaagg agatataaca atgagtaaag gagaagaact tttcactgga gttgtcccaa 60ttcttgttga attagatggt gatgttaatg ggcacaaatt ttctgtcagt ggagagggtg120aaggtgatgc aacatacgga aaacttaccc ttaaatttat ttgcactact ggaaaactac180ctgttccatg gccaacactt gtcactactt tctcttatgg tgttcaatgc ttttcaagat240acccagatca tatgaagcgg cacgacttct tcaagagcgc catgcctgag ggatacgtgc300aggagaggac catctctttc aaggacgacg ggaactacaa gacacgtgct gaagtcaagt360ttgagggaga caccctcgtc aacaggatcg agcttaaggg aatcgatttc aaggaggacg420gaaacatcct cggccacaag ttggaataca actaeaactc ccacaacgta tacatcacgg480cagacaaaca aaagaatgga atcaaagcta acttcaaaat tagacacaac attgaagatg540gaagcgttca actagcagac cattatcaac aaaatactcc aattggcgat ggccctgtcc600ttttaccaga caaccattac ctgtccacac aatctgccct ttcgaaagat cccaacgaaa660agagagacca catggtcctt cttgagtttg taacagctgc tgggattaca catggcatgg720
atgaactata caaataagag ctc 743<210>58<211>25<212>PRT<213>Nicotiana tabacum<400>58Met Asn Phe Leu Lys Ser Phe Pro Phe Tyr Ala Phe Leu Cys Phe Gly1 5 10 15Gln Tyr Phe Val Ala Val Thr His Ala20 25<210>59<211>174<212>PRT<213>Arabidopsis thaliana<400>59Met Val Ser Leu Leu Lys Leu Gln Lys Gln His Arg Thr Leu Asn Pro1 5 10 15Tyr Ser Leu Arg Lys Arg Lys Lys Glu Met Ala Asp His Gln Gln His20 25 30Gln Gln Gln Gln Gln Pro Ile Met Arg Ser Leu His Glu Ser Ser Pro35 40 45Ser Thr Arg Gln Ile Val Arg Phe Val Thr Ala Ala Thr Ile Gly Leu50 55 60Ser Leu Leu Val Leu Ser Gly Leu Thr Leu Thr Gly Thr Val Ile Gly65 70 75 80Leu Ile Val Ala Thr Pro Leu Met Val Leu Phe Ser Pro Val Leu Val85 90 95Pro Ala Val Ile Thr Ile Gly Leu Leu Thr Met Gly Phe Leu Phe Ser100 105 110Gly Gly Cys Gly Val Ala Ala Ala Thr Ala Leu Thr Trp Ile Tyr Lys115 120 125Tyr Val Thr Gly Lys His Pro Met Gly Ala Asp Lys Val Asp Tyr Ala
130 135 140Arg Met Arg Ile Ala Glu Lys Ala Lys Glu Leu Gly His Tyr Thr His145 150 155 160Ser Gln Pro Gln Gln Thr His Gln Thr Thr Thr Thr Thr His165 170<210>60<211>199<212>PRT<213>Arabidopsis thaliana<400>60Met Ala Asp Thr His Arg Val Asp Arg Thr Asp Arg His Phe Gln Phe1 5 10 15Gln Ser Pro Tyr Glu Gly Gly Arg Gly Gln Gly Gln Tyr Glu Gly Asp20 25 30Arg Gly Tyr Gly Gly Gly Gly Tyr Lys Ser Met Met Pro Glu Ser Gly35 40 45Pro Ser Ser Thr Gln Val Leu Ser Leu Leu Ile Gly Val Pro Val Val50 55 60Gly Ser Leu Leu Ala Leu Ala Gly Leu Leu Leu Ala Gly Ser Val Ile65 70 75 80Gly Leu Met Val Ala Leu Pro Leu Phe Leu Leu Phe Ser Pro Val Ile85 90 95Val Pro Ala Ala Leu Thr Ile Gly Leu Ala Met Thr Gly Phe Leu Ala100 105 110Ser Gly Met Phe Gly Leu Thr Gly Leu Ser Ser Ile Ser Trp Val Met115 120 125Asn Tyr Leu Arg Gly Thr Arg Arg Thr Val Pro Glu Gln Leu Glu Tyr130 135 140Ala Lys Arg Arg Met Ala Asp Ala Val Gly Tyr Ala Gly Gln Lys Gly145 150 155 160Lys Glu Met Gly Gln His Val Gln Asn Lys Ala Gln Asp Val Lys Gln
165 170 175Tyr Asp Ile Ser Lys Pro His Asp Thr Thr Thr Lys Gly His Glu Thr180 185 190Gln Gly Arg Thr Thr Ala Ala195<210>61<211>174<212>PRT<213>Arabidopsis thaliana<400>61Met Val Ser Leu Leu Lys Leu Gln Lys Gln His Arg Thr Leu Asn Pro1 5 10 15Tyr Ser Leu Arg Lys Arg Lys Lys Glu Met Ala Asp His Gln Gln His20 25 30Gln Gln Gln Gln Gln Pro Ile Met Arg Ser Leu His Glu Ser Ser Pro35 40 45Ser Thr Arg Gln Ile Val Arg Phe Val Thr Ala Ala Thr Ile Gly Leu50 55 60Ser Leu Leu Val Leu Ser Gly Leu Thr Leu Thr Gly Thr Val Ile Gly65 70 75 80Leu Ile Val Ala Thr Pro Leu Met Val Leu Phe Ser Pro Val Leu Val85 90 95Pro Ala Val Ile Thr Ile Gly Leu Leu Thr Met Gly Phe Leu Phe Ser100 105 110Gly Gly Cys Gly Val Ala Ala Ala Thr Ala Leu Thr Trp Ile Tyr Lys115 120 125Tyr Val Thr Gly Lys His Pro Met Gly Ala Asp Lys Val Asp Tyr Ala130 135 140Arg Met Arg Ile Ala Glu Lys Ala Lys Glu Leu Gly His Tyr Thr His145 150 155 160Ser Gln Pro Gln Gln Thr His Gln Thr Thr Thr Thr Thr His
165 170<210>62<211>183<212>PRT<213>Arabidopsis thaliana<400>62Met Ala Asp Val Arg Thr His Ser His Gln Leu Gln Val His Pro Gln1 5 10 15Arg Gln His Glu Gly Gly Ile Lys Val Leu Tyr Pro Gln Ser Gly Pro20 25 30Ser Ser Thr Gln Val Leu Ala Val Phe Val Gly Val Pro Ile Gly Gly35 40 45Thr Leu Leu Thr Ile Ala Gly Leu Thr Leu Ala Gly Ser Val Ile Gly50 55 60Leu Met Leu Ala Phe Pro Leu Phe Leu Ile Phe Ser Pro Val Ile Val65 70 75 80Pro Ala Ala Phe Val Ile Gly Leu Ala Met Thr Gly Phe Leu Ala Ser85 90 95Gly Ala Ile Gly Leu Thr Gly Leu Ser Ser Met Ser Trp Val Leu Asn100 105 110Tyr Ile Arg Arg Ala Gly Gln His Ile Pro Glu Glu Leu Glu Glu Ala115 120 125Lys His Arg Leu Ala Asp Met Ala Glu Tyr Val Gly Gln Arg Thr Lys130 135 140Asp Ala Gly Gln Thr Ile Glu Asp Lys Ala His Asp Val Arg Glu Ala145 150 155 160Lys Thr Phe Asp Val Arg Asp Arg Asp Thr Thr Lys Gly Thr His Asn165 170 175Val Arg Asp Thr Lys Thr Thr180<210>63
<211>169<212>PRT<213>Arabidopsis thaliana<400>63Met Ala Asp Arg Thr Asn Pro Ser Ser His Thr Gln Gln Arg Pro Ile1 5 10 15Tyr Asn Ser Thr Thr Val Pro Arg Ser Asn Thr Thr Thr Asn His Pro20 25 30Leu Ser Ser Leu Leu Arg Gln Leu Leu Gln Ser Gln Ser Pro Asn His35 40 45Ser Gly Gln Leu Phe Gly Phe Leu Ala Phe Phe Ile Ser Gly Gly Ile50 55 60Leu Leu Leu Leu Thr Gly Ile Thr Val Thr Ala Phe Val Leu Gly Phe65 70 75 80Ile Ala Phe Leu Pro Leu Ile Ile Ile Ser Ser Pro Ile Trp Ile Pro85 90 95Leu Phe Leu Ile Val Thr Gly Phe Leu Ser Leu Ala Gly Leu Ile Leu100 105 110Ala Thr Gly Ala Val Val Ser Trp Leu Tyr Arg Tyr Phe Lys Gly Met115 120 125His Pro Leu Arg Ser Asp Gln Val Asp Tyr Ala Arg Ser Arg Ile His130 135 140Asp Thr Ala Ala His Val Lys Asp Tyr Ala Gly Gly Tyr Phe His Gly145 150 155 160Thr Leu Lys Asp Ala Ala Pro Gly Ala165<210>64<211>191<212>PRT<213>Arabidopsis thaliana<400>64Met Ala Asn Val Asp Arg Asp Arg Arg Val His Val Asp Arg Thr Asp1 5 10 15
Lys Arg Val His Gln Pro Asn Tyr Glu Asp Asp Val Gly Phe Gly Gly20 25 30Tyr Gly Gly Tyr Gly Ala Gly Ser Asp Tyr Lys Ser Arg Gly Pro Ser35 40 45Thr Asn Gln Ile Leu Ala Leu Ile Ala Gly Val Pro Ile Gly Gly Thr50 55 60Leu Leu Thr Leu Ala Gly Leu Thr Leu Ala Gly Ser Val Ile Gly Leu65 70 75 80Leu Val Ser Ile Pro Leu Phe Leu Leu Phe Ser Pro Val Ile Val Pro85 90 95Ala Ala Leu Thr Ile Gly Leu Ala Val Thr Gly Ile Leu Ala Ser Gly100 105 110Leu Phe Gly Leu Thr Gly Leu Ser Ser Val Ser Trp Val Leu Asn Tyr115 120 125Leu Arg Gly Thr Ser Asp Thr Val Pro Glu Gln Leu Asp Tyr Ala Lys130 135 140Arg Arg Met Ala Asp Ala Val Gly Tyr Ala Gly Met Lys Gly Lys Glu145 150 155 160Met Gly Gln Tyr Val Gln Asp Lys Ala His Glu Ala Arg Glu Thr Glu165 170 175Phe Met Thr Glu Thr His Glu Pro Gly Lys Ala Arg Arg Gly Ser180 185 190<210>65<211>199<212>PRT<213>Arabidopsis thaliana<400>65Met Ala Asp Thr His Arg Val Asp Arg Thr Asp Arg His Phe Gln Phe1 5 10 15Gln Ser Pro Tyr Glu Gly Gly Arg Gly Gln Gly Gln Tyr Glu Gly Asp20 25 30
Arg Gly Tyr Gly Gly Gly Gly Tyr Lys Ser Met Met Pro Glu Ser Gly35 40 45Pro Ser Ser Thr Gln Val Leu Ser Leu Leu Ile Gly Val Pro Val Val50 55 60Gly Ser Leu Leu Ala Leu Ala Gly Leu Leu Leu Ala Gly Ser Val Ile65 70 75 80Gly Leu Met Val Ala Leu Pro Leu Phe Leu Leu Phe Ser Pro Val Ile85 90 95Val Pro Ala Ala Leu Thr Ile Gly Leu Ala Met Thr Gly Phe Leu Ala100 105 110Ser Gly Met Phe Gly Leu Thr Gly Leu Ser Ser Ile Ser Trp Val Met115 120 125Asn Tyr Leu Arg Gly Thr Arg Arg Thr Val Pro Glu Gln Leu Glu Tyr130 135 140Ala Lys Arg Arg Met Ala Asp Ala Val Gly Tyr Ala Gly Gln Lys Gly145 150 155 160Lys Glu Met Gly Gln His Val Gln Asn Lys Ala Gln Asp Val Lys Gln165 170 175Tyr Asp Ile Ser Lys Pro His Asp Thr Thr Thr Lys Gly His Glu Thr180 185 190Gln Gly Arg Thr Thr Ala Ala195<210>66<211>183<212>PRT<213>Arabidopsis thaliana<400>66Met Ala Asp Val Arg Thr His Ser His Gln Leu Gln Val His Pro Gln1 5 10 15Arg Gln His Glu Gly Gly Ile Lys Val Leu Tyr Pro Gln Ser Gly Pro20 25 30
Ser Ser Thr Gln Val Leu Ala Val Phe Val Gly Val Pro Ile Gly Gly35 40 45Thr Leu Leu Thr Ile Ala Gly Leu Thr Leu Ala Gly Ser Val Ile Gly50 55 60Leu Met Leu Ala Phe Pro Leu Phe Leu Ile Phe Ser Pro Val Ile Val65 70 75 80Pro Ala Ala Phe Val Ile Gly Leu Ala Met Thr Gly Phe Leu Ala Ser85 90 95Gly Ala Ile Gly Leu Thr Gly Leu Ser Ser Met Ser Trp Val Leu Asn100 105 110Tyr Ile Arg Arg Ala Gly Gln His Ile Pro Glu Glu Leu Glu Glu Ala115 120 125Lys His Arg Leu Ala Asp Met Ala Glu Tyr Val Gly Gln Arg Thr Lys130 135 140Asp Ala Gly Gln Thr Ile Glu Asp Lys Ala His Asp Val Arg Glu Ala145 150 155 160Lys Thr Phe Asp Val Arg Asp Arg Asp Thr Thr Lys Gly Thr His Asn165 170 175Val Arg Asp Thr Lys Thr Thr180<210>67<211>191<212>PRT<213>Arabidopsis thaliana<400>67Met Ala Asn Val Asp Arg Asp Arg Arg Val His Val Asp Arg Thr Asp1 5 l0 15Lys Arg Val His Gln Pro Asn Tyr Glu Asp Asp Val Gly Phe Gly Gly20 25 30Tyr Gly Gly Tyr Gly Ala Gly Ser Asp Tyr Lys Ser Arg Gly Pro Ser35 40 45
Thr Asn Gln Ile Leu Ala Leu Ile Ala Gly Val Pro Ile Gly Gly Thr50 55 60Leu Leu Thr Leu Ala Gly Leu Thr Leu Ala Gly Ser Val Ile Gly Leu65 70 75 80Leu Val Ser Ile Pro Leu Phe Leu Leu Phe Ser Pro Val Ile Val Pro85 90 95Ala Ala Leu Thr Ile Gly Leu Ala Val Thr Gly Ile Leu Ala Ser Gly100 105 110Leu Phe Gly Leu Thr Gly Leu Ser Ser Val Ser Trp Val Leu Asn Tyr115 120 125Leu Arg Gly Thr Ser Asp Thr Val Pro Glu Gln Leu Asp Tyr Ala Lys130 135 140Arg Arg Met Ala Asp Ala Val Gly Tyr Ala Gly Met Lys Gly Lys Glu145 150 155 160Met Gly Gln Tyr Val Gln Asp Lys Ala His Glu Ala Arg Glu Thr Glu165 170 175Phe Met Thr Glu Thr His Glu Pro Gly Lys Ala Arg Arg Gly Ser180 185 190<210>68<211>183<212>PRT<213>Arabidopsis thaliana<400>68Met Ala Asp Val Arg Thr His Ser His Gln Leu Gln Val His Pro Gln1 5 10 15Arg Gln His Glu Gly Gly Ile Lys Val Leu Tyr Pro Gln Ser Gly Pro20 25 30Ser Ser Thr Gln Val Leu Ala Val Phe Val Gly Val Pro Ile Gly Gly35 40 45Thr Leu Leu Thr Ile Ala Gly Leu Thr Leu Ala Gly Ser Val Ile Gly50 55 60
Leu Met Leu Ala Phe Pro Leu Phe Leu Ile Phe Ser Pro Val Ile Val65 70 75 80Pro Ala Ala Phe Val Ile Gly Leu Ala Met Thr Gly Phe Leu Ala Ser85 90 95Gly Ala Ile Gly Leu Thr Gly Leu Ser Ser Met Ser Trp Val Leu Asn100 105 110Tyr Ile Arg Arg Ala Gly Gln His Ile Pro Glu Glu Leu Glu Glu Ala115 120 125Lys His Arg Leu Ala Asp Met Ala Glu Tyr Val Gly Gln Arg Thr Lys130 135 140Asp Ala Gly Gln Thr Ile Glu Asp Lys Ala His Asp Val Arg Glu Ala145 150 155 160Lys Thr Phe Asp Val Arg Asp Arg Asp Thr Thr Lys Gly Thr His Asn165 170 175Val Arg Asp Thr Lys Thr Thr180<210>69<211>199<212>PRT<213>Arabidopsis thaliana<400>69Met Ala Asp Thr His Arg Val Asp Arg Thr Asp Arg His Phe Gln Phe1 5 10 15Gln Ser Pro Tyr Glu Gly Gly Arg Gly Gln Gly Gln Tyr Glu Gly Asp20 25 30Arg Gly Tyr Gly Gly Gly Gly Tyr Lys Ser Met Met Pro Glu Ser Gly35 40 45Pro Ser Ser Thr Gln Val Leu Ser Leu Leu Ile Gly Val Pro Val Val50 55 60Gly Ser Leu Leu Ala Leu Ala Gly Leu Leu Leu Ala Gly Ser Val Ile65 70 75 80
Gly Leu Met Val Ala Leu Pro Leu Phe Leu Leu Phe Ser Pro Val Ile85 90 95Val Pro Ala Ala Leu Thr Ile Gly Leu Ala Met Thr Gly Phe Leu Ala100 105 110Ser Gly Met Phe Gly Leu Thr Gly Leu Ser Ser Ile Ser Trp Val Met115 120 125Asn Tyr Leu Arg Gly Thr Arg Arg Thr Val Pro Glu Gln Leu Glu Tyr130 135 140Ala Lys Arg Arg Met Ala Asp Ala Val Gly Tyr Ala Gly Gln Lys Gly145 150 155 160Lys Glu Met Gly Gln His Val Gln Asn Lys Ala Gln Asp Val Lys Gln165 170 175Tyr Asp Ile Ser Lys Pro His Asp Thr Thr Thr Lys Gly His Glu Thr180 185 190Gln Gly Arg Thr Thr Ala Ala195<210>70<211>191<212>PRT<213>Arabidopsis thaliana<220>
<221>misc_feature<222>(160)..(160)<223>Xaa can be any naturally occurring amino acid<400>70Met Ala Asn Val Asp Arg Asp Arg Arg Val His Val Asp Arg Thr Asp1 5 10 15Lys Arg Val His Gln Pro Asn Tyr Glu Asp Asp Val Gly Phe Gly Gly20 25 30Tyr Gly Gly Tyr Gly Ala Gly Ser Asp Tyr Lys Ser Arg Gly Pro Ser35 40 45
Thr Asn Gln Ile Leu Ala Leu Ile Ala Gly Val Pro Ile Gly Gly Thr50 55 60Leu Leu Thr Leu Ala Gly Leu Thr Leu Ala Gly Ser Val Ile Gly Leu65 70 75 80Leu Val Ser Ile Pro Leu Phe Leu Leu Phe Ser Pro Val Ile Val Pro85 90 95Ala Ala Leu Thr Ile Gly Leu Ala Val Thr Gly Ile Leu Ala Ser Gly100 105 110Leu Phe Gly Leu Thr Gly Leu Ser Ser Val Ser Trp Val Leu Asn Tyr115 120 125Leu Arg Gly Thr Ser Asp Thr Val Pro Glu Gln Leu Asp Tyr Ala Lys130 135 140Arg Arg Met Ala Asp Ala Val Ser Tyr Ala Gly Met Lys Gly Lys Xaa145 150 155 160Met Gly Gln Tyr Val Gln Asp Lys Ala His Glu Ala Arg Glu Thr Glu165 170 175Phe Met Thr Glu Thr His Glu Pro Gly Lys Ala Arg Arg Gly Ser180 185 190<210>71<211>141<212>PRT<213>Arabidopsis thaliana<400>71Met Ala Asp Gln Thr Arg Thr His His Glu Met Ile Ser Arg Asp Ser1 5 10 15Thr Gln Glu Ala His Pro Lys Ala Arg Gln Met Val Lys Ala Ala Thr20 25 30Ala Val Thr Ala Gly Gly Ser Leu Leu Val Leu Ser Gly Leu Thr Leu35 40 45Ala Gly Thr Val Val Ala Leu Thr Val Ala Thr Pro Leu Leu Val Ile50 55 60
Phe Ser Pro Val Leu Val Pro Ala Val Val Thr Val Ala Leu Ile Ile65 70 75 80Thr Gly Phe Leu Ala Ser Gly Gly Phe Gly Ile Ala Ala Ile Thr Ala85 90 95Phe Ser Trp Leu Tyr Arg His Met Thr Gly Ser Gly Ser Asp Lys Ile100 105 110Glu Asn Ala Arg Met Lys Val Gly Ser Arg Val Gln Asp Thr Lys Tyr115 120 125Gly Gln His Asn Ile Gly Val Gln His Gln Gln Val Ser130 135 140<210>72<211>167<212>PRT<213>Arabidopsis thaliana<400>72Gln Lys Gln His Arg Thr Leu Asn Pro Tyr Ser Leu Arg Lys Arg Lys1 5 10 15Lys Glu Met Ala Asp His Gln Gln His Gln Gln Gln Gln Gln Pro Ile20 25 30Met Arg Ser Leu His Glu Ser Ser Pro Ser Thr Arg Gln Ile Val Arg35 40 45Phe Val Thr Ala Ala Thr Ile Gly Leu Ser Leu Leu Val Leu Ser Gly50 55 60Leu Thr Leu Thr Gly Thr Val Ile Gly Leu Ile Val Ala Thr Pro Leu65 70 75 80Met Val Leu Phe Ser Pro Val Leu Val Pro Ala Val Ile Thr Ile Gly85 90 95Leu Leu Thr Met Gly Phe Leu Phe Ser Gly Gly Cys Gly Val Ala Ala100 105 110Ala Thr Ala Leu Thr Trp Ile Tyr Lys Tyr Val Thr Gly Lys His Pro115 120 125
Met Gly Ala Asp Lys Val Asp Tyr Ala Arg Met Arg Ile Ala Glu Lys130 135 140Ala Lys Glu Leu Gly His Tyr Thr His Ser Gln Pro Gln Gln Thr His145 150 155 160Gln Thr Thr Thr Thr Thr His165<210>73<211>166<212>PRT<213>Arabidopsis thaliana<400>73Met Ala Glu Arg Phe Ser Ser Gly Glu Ala Gln Tyr Trp Pro Asn Tyr1 5 10 15Gly Ser Thr Ala Thr Thr Thr Val Ser Asn Ser Pro Ile Ser Ser Phe20 25 30Phe His Gln Leu Arg Ser His Ser Pro Thr Ser Ser Gln Leu Phe Gly35 40 45Phe Leu Ala Leu Phe Ile Ser Thr Gly Ile Leu Leu Phe Leu Leu Gly50 55 60Val Ser Val Thr Ala Ala Val Leu Gly Phe Ile Val Phe Leu Pro Leu65 70 75 80Ile Ile Ile Ser Ser Pro Ile Trp Ile Pro Val Phe Val Val Val Gly85 90 95Gly Phe Leu Thr Val Ser Gly Phe Leu Val Gly Thr Val Ala Leu Val100 105 110Ser Trp Thr Tyr Arg Tyr Phe Arg Gly Met His Pro Val Gly Ser Asn115 120 125Gln Met Asp Tyr Ala Arg Ser Arg Ile Tyr Asp Thr Ala Ser His Val130 135 140Lys Asp Tyr Ala Arg Glu Tyr Gly Gly Tyr Phe His Gly Arg Ala Lys145 150 155 160
Asp Ala Ala Pro Gly Ala165<210>74<211>166<212>PRT<213>Arabidopsis thaliana<400>74Met Ala Glu Arg Phe Ser Ser Gly Glu Ala Gln Tyr Trp Pro Asn Tyr1 5 10 15Gly Ser Thr Ala Thr Thr Thr Val Ser Asn Ser Pro Ile Ser Ser Phe20 25 30Phe His Gln Leu Arg Ser His Ser Pro Thr Ser Ser Gln Leu Phe Gly35 40 45Phe Leu Ala Leu Phe Ile Ser Thr Gly Ile Leu Leu Phe Leu Leu Gly50 55 60Val Ser Val Thr Ala Ala Val Leu Gly Phe Ile Val Phe Leu Pro Leu65 70 75 80Ile Ile Ile Ser Ser Pro Ile Trp Ile Pro Val Phe Val Val Val Gly85 90 95Gly Phe Leu Thr Val Ser Gly Phe Leu Val Gly Thr Val Ala Leu Val100 105 110Ser Trp Thr Tyr Arg Tyr Phe Arg Gly Met His Pro Val Gly Ser Asn115 120 125Gln Met Asp Tyr Ala Arg Ser Arg Ile Tyr Asp Thr Ala Ser His Val130 135 140Lys Asp Tyr Ala Arg Glu Tyr Gly Gly Tyr Phe His Gly Arg Ala Lys145 150 155 160Asp Ala Ala Pro Gly Ala165<210>75<211>169<212>PRT<213>Arabidopsis thaliana
<400>75Met Ala Asp Arg Thr Asn Pro Ser Ser His Thr Gln Gln Arg Pro Ile1 5 10 15Tyr Asn Ser Thr Thr Val Pro Arg Ser Asn Thr Thr Thr Asn His Pro20 25 30Leu Ser Ser Leu Leu Arg Gln Leu Leu Gln Ser Gln Ser Pro Asn His35 40 45Ser Gly Gln Leu Phe Gly Phe Leu Ala Phe Phe Ile Ser Gly Gly Ile50 55 60Leu Leu Leu Leu Thr Gly Ile Thr Val Thr Ala Phe Val Leu Gly Phe65 70 75 80Ile Ala Phe Leu Pro Leu Ile Ile Ile Ser Ser Pro Ile Trp Ile Pro85 90 95Leu Phe Leu Ile Val Thr Gly Phe Leu Ser Leu Ala Gly Leu Ile Leu100 105 110Ala Thr Gly Ala Val Val Ser Trp Leu Tyr Arg Tyr Phe Lys Gly Met115 120 125His Pro Leu Arg Ser Asp Gln Val Asp Tyr Ala Arg Ser Arg Ile His130 135 140Asp Thr Ala Ala His Val Lys Asp Tyr Ala Gly Gly Tyr Phe His Gly145 150 155 160Thr Leu Lys Asp Ala Ala Pro Gly Ala165<210>76<211>226<212>PRT<213>Arabidopsis lyrata<400>76Met Phe Ser Phe Leu Ile Leu Leu Leu Glu Val Tyr Lys Val Val Ile1 5 10 15Ala Val Val Ala Ser Ile Val Phe Phe Val Phe Ser Gly Leu Thr Leu
20 25 30Ala Gly Ser Ala Val Ala Leu Thr Val Thr Thr Pro Leu Phe Ile Ile35 40 45Phe Ser Pro Ile Leu Val Pro Ala Thr Ile Ala Thr Ala Leu Leu Thr50 55 60Thr Gly Phe Thr Ala Gly Gly Ala Leu Gly Ala Thr Ala Ile Ala Leu65 70 75 80Ile Arg Arg Ser Met Gly Val Lys Ser Lys Asn Asn Ile Pro Ala Thr85 90 95Gly Ala Pro Pro Thr Met Phe Ala Gln Thr Pro Phe Asn Leu Thr Pro100 105 110Lys Ile Asn Tyr Glu Gly Thr Phe Lys Gly Ser Trp Gly Gly Thr Ser115 120 125Ser Pro Gln Ala Ala Pro Asn Phe Ser Tyr Gly Gly Thr Trp Thr Ala130 135 140Thr Trp Gly Gly Arg Ser Phe Thr Gly Lys Phe Gly Asp Gln Ser Gly145 150 155 160Gly Gly Gly Ser Thr Pro Glu Ala Ala Gly Ala Ala Ala Asp Ala Gly165 170 175Ala Gly Ala Gly Ala Gly Ala Gly Ala Gly Ala Gly Ala Gly Ala Gly180 185 190Ala Ala Gly Ala Gly Ala Gly Ala Gly Ala Gly Ala Gly Ala Pro Gly195 200 205Gly Ala Gly Thr Gly Thr Pro Ala Pro Pro Gly Lys Ala Gly Ser Lys210 215 220Lys Lys225<210>77<211>141<212>PRT<213>Arsbidopsis thaliana
<400>77Met Ala Asp Gln Thr Arg Thr His His Glu Met Ile Ser Arg Asp Ser1 5 10 15Thr Gln Glu Ala His Pro Lys Ala Arg Gln Met Val Lys Ala Ala Thr20 25 30Ala Val Thr Ala Gly Gly Ser Leu Leu Val Leu Ser Gly Leu Thr Leu35 40 45Ala Gly Thr Val Ile Ala Leu Thr Val Ala Thr Pro Leu Leu Val Ile50 55 60Phe Ser Pro Val Leu Val Pro Ala Val Val Thr Val Ala Leu Ile Ile65 70 75 80Thr Gly Phe Leu Ala Ser Gly Gly Phe Gly Ile Ala Ala Ile Thr Ala85 90 95Phe Ser Trp Leu Tyr Arg His Met Thr Gly Ser Gly Ser Asp Lys Ile100 105 110Glu Asn Ala Arg Met Lys Val Gly Ser Arg Val Gln Asp Thr Lys Tyr115 120 125Gly Gln His Asn Ile Gly Val Gln His Gln Gln Val Ser130 135 140<210>78<211>191<212>PRT<213>Arabidopsis thaliana<400>78Met Ala Asn Val Asp Arg Asp Arg Arg Val His Val Asp Arg Thr Asp1 5 10 15Lys Arg Val His Gln Pro Asn Tyr Glu Asp Asp Val Gly Phe Gly Gly20 25 30Tyr Gly Gly Tyr Gly Ala Gly Ser Asp Tyr Lys Ser Arg Gly Pro Ser35 40 45Thr Asn Gln Ile Leu Ala Leu Ile Ala Gly Val Pro Ile Gly Gly Thr
50 55 60Leu Leu Thr Leu Ala Gly Leu Thr Leu Ala Gly Ser Val Ile Gly Leu65 70 75 80Leu Val Ser Ile Pro Leu Phe Leu Leu Phe Ser Pro Val Ile Val Pro85 90 95Ala Ala Leu Thr Ile Gly Leu Ala Val Thr Gly Ile Leu Ala Ser Gly100 105 110Leu Phe Gly Leu Thr Gly Leu Ser Ser Val Ser Trp Val Leu Asn Tyr115 120 125Leu Arg Gly Thr Ser Asp Thr Val Pro Glu Gln Leu Asp Tyr Ala Lys130 135 140Arg Arg Met Ala Asp Ala Val Gly Tyr Ala Gly Met Lys Gly Lys Glu145 150 155 160Met Gly Gln Tyr Val Gln Asp Lys Ala His Glu Ala Arg Glu Thr Glu165 170 175Phe Met Thr Glu Thr His Glu Pro Gly Lys Ala Arg Arg Gly Ser180 185 190<210>79<211>199<212>PRT<213>Arabidopsis thaliana<400>79Met Ala Asp Thr His Arg Val Asp Arg Thr Asp Arg His Phe Gln Phe1 5 10 15Gln Ser Pro Tyr Glu Gly Gly Arg Gly Gln Gly Gln Tyr Glu Gly Asp20 25 30Arg Gly Tyr Gly Gly Gly Gly Tyr Lys Ser Met Met Pro Glu Ser Gly35 40 45Pro Ser Ser Thr Gln Val Leu Ser Leu Leu Ile Gly Val Pro Val Val50 55 60Gly Ser Leu Leu Ala Leu Ala Gly Leu Leu Leu Ala Gly Ser Val Ile
65 70 75 80Gly Leu Met Val Ala Leu Pro Leu Phe Leu Leu Phe Ser Pro Val Ile85 90 95Val Pro Ala Ala Leu Thr Ile Gly Leu Ala Met Thr Gly Phe Leu Ala100 105 110Ser Gly Met Phe Gly Leu Thr Gly Leu Ser Ser Ile Ser Trp Val Met115 120 125Asn Tyr Leu Arg Gly Thr Arg Arg Thr Val Pro Glu Gln Leu Glu Tyr130 135 140Ala Lys Arg Arg Met Ala Asp Ala Val Gly Tyr Ala Gly Gln Lys Gly145 150 155 160Lys Glu Met Gly Gln His Val Gln Asn Lys Ala Gln Asp Val Lys Gln165 170 175Tyr Asp Ile Ser Lys Pro His Asp Thr Thr Thr Lys Gly His Glu Thr180 185 190Gln Gly Arg Thr Thr Ala Ala195<210>80<211>169<212>PRT<213>Arabidopsis thaliana<400>80Met Ala Asp Arg Thr Asn Pro Ser Ser His Thr Gln Gln Arg Pro Ile1 5 10 15Tyr Asn Ser Thr Thr Val Pro Arg Ser Asn Thr Thr Thr Asn His Pro20 25 30Leu Ser Ser Leu Leu Arg Gln Leu Leu Gln Ser Gln Ser Pro Asn His35 40 45Ser Gly Gln Leu Phe Gly Phe Leu Ala Phe Phe Ile Ser Gly Gly Ile50 55 60Leu Leu Leu Leu Thr Gly Ile Thr Val Thr Ala Phe Val Leu Gly Phe
65 70 75 80Ile Ala Phe Leu Pro Leu Ile Ile Ile Ser Ser Pro Ile Trp Ile Pro85 90 95Leu Phe Leu Ile Val Thr Gly Phe Leu Ser Leu Ala Gly Leu Ile Leu100 105 110Ala Thr Gly Ala Val Val Ser Trp Leu Tyr Arg Tyr Phe Lys Gly Met115 120 125His Pro Leu Arg Ser Asp Gln Val Asp Tyr Ala Arg Ser Arg Ile His130 135 140Asp Thr Ala Ala His Val Lys Asp Tyr Ala Gly Gly Tyr Phe His Gly145 150 155 160Thr Leu Lys Asp Ala Ala Pro Gly Ala165<210>81<211>173<212>PRT<213>Arabidopsis thaliana<400>81Met Ala Asp Thr Ala Arg Gly Thr His His Asp Ile Ile Gly Arg Asp1 5 10 15Gln Tyr Pro Met Met Gly Arg Asp Arg Asp Gln Tyr Gln Met Ser Gly20 25 30Arg Gly Ser Asp Tyr Ser Lys Ser Arg Gln Ile Ala Lys Ala Ala Thr35 40 45Ala Val Thr Ala Gly Gly Ser Leu Leu Val Leu Ser Ser Leu Thr Leu50 55 60Val Gly Thr Val Ile Ala Leu Thr Val Ala Thr Pro Leu Leu Val Ile65 70 75 80Phe Ser Pro Ile Leu Val Pro Ala Leu Ile Thr Val Ala Leu Leu Ile85 90 95Thr Gly Phe Leu Ser Ser Gly Gly Phe Gly Ile Ala Ala Ile Thr Val
100 105 110Phe Ser Trp Ile Tyr Lys Tyr Ala Thr Gly Glu His Pro Gln Gly Ser115 120 125Asp Lys Leu Asp Ser Ala Arg Met Lys Leu Gly Ser Lys Ala Gln Asp130 135 140Leu Lys Asp Arg Ala Gln Tyr Tyr Gly Gln Gln His Thr Gly Gly Glu145 150 155 160His Asp Arg Asp Arg Thr Arg Gly Gly Gln His Thr Thr165 170<210>82<211>191<212>PRT<213>Arabidopsis thaliana<400>82Met Ala Asn Val Asp Arg Asp Arg Arg Val His Val Asp Arg Thr Asp1 5 10 15Lys Arg Val His Gln Pro Asn Tyr Glu Asp Asp Val Gly Phe Gly Gly20 25 30Tyr Gly Gly Tyr Gly Ala Gly Ser Asp Tyr Lys Ser Arg Gly Pro Ser35 40 45Thr Asn Gln Ile Leu Ala Leu Ile Ala Gly Val Pro Ile Gly Gly Thr50 55 60Leu Leu Thr Leu Ala Gly Leu Thr Leu Ala Gly Ser Val Ile Gly Leu65 70 75 80Leu Val Ser Ile Pro Leu Phe Leu Leu Phe Ser Pro Val Ile Val Pro85 90 95Ala Ala Leu Thr Ile Gly Leu Ala Val Thr Gly Ile Leu Ala Ser Gly100 105 110Leu Phe Gly Leu Thr Gly Leu Ser Ser Val Ser Trp Val Leu Asn Tyr115 120 125Leu Arg Gly Thr Ser Asp Thr Val Pro Glu Gln Leu Asp Tyr Ala Lys
130 135 140Arg Arg Met Ala Asp Ala Val Gly Tyr Ala Gly Met Lys Gly Lys Glu145 150 155 160Met Gly Gln Tyr Val Gln Asp Lys Ala His Glu Ala Arg Glu Thr Glu165 170 175Phe Met Thr Glu Thr His Glu Pro Gly Lys Ala Arg Arg Gly Pro180 185 190<210>83<211>199<212>PRT<213>Arabidopsis thaliana<400>83Met Ala Asp Thr His Arg Val Asp Arg Thr Asp Arg His Phe Gln Phe1 5 10 15Gln Ser Pro Tyr Glu Gly Gly Arg Gly Gln Gly Gln Tyr Glu Gly Asp20 25 30Arg Gly Tyr Gly Gly Gly Gly Tyr Lys Ser Met Met Pro Glu Ser Gly35 40 45Pro Ser Ser Thr Gln Val Leu Ser Leu Leu Ile Gly Val Pro Val Val50 55 60Gly Ser Leu Leu Ala Leu Ala Gly Leu Leu Leu Ala Gly Ser Val Ile65 70 75 80Gly Leu Met Val Ala Leu Pro Leu Phe Leu Leu Phe Ser Pro Val Ile85 90 95Val Pro Ala Gly Leu Thr Ile Gly Leu Ala Met Thr Gly Phe Leu Ala100 105 110Ser Gly Met Phe Gly Leu Thr Gly Leu Ser Ser Ile Ser Trp Val Met115 120 125Asn Tyr Leu Arg Gly Thr Lys Arg Thr Val Pro Glu Gln Leu Glu Tyr130 135 140Ala Lys Arg Arg Met Ala Asp Ala Val Gly Tyr Ala Gly Gln Lys Gly
145 150 155 160Lys Glu Met Gly Gln His Val Gln Asn Lys Ala Gln Asp Val Lys Gln165 170 175Tyr Asp Ile Ser Lys Pro His Asp Thr Thr Thr Lys Gly His Glu Thr180 185 190Gln Gly Gly Thr Thr Ala Ala195<210>84<211>191<212>PRT<213>Arabidopsis thaliana<400>84Met Ala Asn Val Asp Arg Asp Arg Arg Val His Val Asp Arg Thr Asp1 5 10 15Lys Arg Val His Gln Pro Asn Tyr Glu Asp Asp Val Gly Phe Gly Gly20 25 30Tyr Gly Gly Tyr Gly Ala Gly Ser Asp Tyr Lys Ser Arg Gly Pro Ser35 40 45Thr Asn Gln Ile Leu Ala Leu Ile Ala Gly Val Pro Ile Gly Gly Thr50 55 60Leu Leu Thr Leu Ala Gly Leu Thr Leu Ala Gly Ser Val Ile Gly Leu65 70 75 80Leu Val Ser Ile Pro Leu Phe Leu Leu Phe Ser Pro Val Ile Val Pro85 90 95Ala Ala Leu Thr Ile Gly Leu Ala Val Thr Gly Ile Leu Ala Ser Gly100 105 110Leu Phe Gly Leu Thr Gly Leu Ser Ser Val Ser Trp Val Leu Asn Tyr115 120 125Leu Arg Gly Thr Ser Asp Thr Val Pro Glu Gln Leu Asp Tyr Ala Lys130 135 140Arg Arg Met Ala Asp Ala Val Gly Tyr Ala Gly Met Lys Gly Lys Glu
145 150 155 160Met Gly Gln Tyr Val Gln Asp Lys Ala His Glu Ala Arg Glu Thr Glu165 170 175Phe Met Thr Glu Thr His Glu Pro Gly Lys Ala Arg Arg Gly Ser180 185 190<210>85<211>141<212>PRT<213>Arabidopsis thaliana<400>85Met Ala Asp Gln Thr Arg Thr His His Glu Met Ile Ser Arg Asp Ser1 5 10 15Thr Gln Glu Ala His Pro Lys Ala Arg Gln Met Val Lys Ala Ala Thr20 25 30Ala Val Thr Ala Gly Gly Ser Leu Leu Val Leu Ser Gly Leu Thr Leu35 40 45Ala Gly Thr Val Ile Ala Leu Thr Val Ala Thr Pro Leu Leu Val Ile50 55 60Phe Ser Pro Val Leu Val Pro Ala Val Val Thr Val Ala Leu Ile Ile65 70 75 80Thr Gly Phe Leu Ala Ser Gly Gly Phe Gly Ile Ala Ala Ile Thr Ala85 90 95Phe Ser Trp Leu Tyr Arg His Met Thr Gly Ser Gly Ser Asp Lys Ile100 105 110Glu Asn Ala Arg Met Lys Val Gly Ser Arg Val Gln Asp Thr Lys Tyr115 120 125Gly Gln His Asn Ile Gly Val Gln His Gln Gln Val Ser130 135 140<210>86<211>173<212>PRT<213>Arabidopsis thaliana
<400>86Met Ala Asp Thr Ala Arg Gly Thr His His Asp Ile Ile Gly Arg Aspl 5 10 15Gln Tyr Pro Met Met Gly Arg Asp Arg Asp Gln Tyr Gln Met Ser Gly20 25 30Arg Gly Ser Asp Tyr Ser Lys Ser Arg Gln Ile Ala Lys Ala Ala Thr35 40 45Ala Val Thr Ala Gly Gly Ser Leu Leu Val Leu Ser Ser Leu Thr Leu50 55 60Val Gly Thr Val Ile Ala Leu Thr Val Ala Thr Pro Leu Leu Val Ile65 70 75 80Phe Ser Pro Ile Leu Val Pro Ala Leu Ile Thr Val Ala Leu Leu Ile85 90 95Thr Gly Phe Leu Ser Ser Gly Gly Phe Gly Ile Ala Ala Ile Thr Val100 105 110Phe Ser Trp Ile Tyr Lys Tyr Ala Thr Gly Glu His Pro Gln Gly Ser115 120 125Asp Lys Leu Asp Ser Ala Arg Met Lys Leu Gly Ser Lys Ala Gln Asp130 135 140Leu Lys Asp Arg Ala Gln Tyr Tyr Gly Gln Gln His Thr Gly Gly Glu145 150 155 160His Asp Arg Asp Arg Thr Arg Gly Gly Gln His Thr Thr165 170<210>87<211>173<212>PRT<213>Arabidopsis thaliana<400>87Met Ala Asp Thr Ala Arg Gly Thr His His Asp Ile Ile Gly Arg Asp1 5 10 15Gln Tyr Pro Met Met Gly Arg Asp Arg Asp Gln Tyr Gln Met Ser Gly20 25 30
Arg Gly Ser Asp Tyr Ser Lys Ser Arg Gln Ile Ala Lys Ala Ala Thr35 40 45Ala Val Thr Ala Gly Gly Ser Leu Leu Val Leu Ser Ser Leu Thr Leu50 55 60Val Gly Thr Val Ile Ala Leu Thr Val Ala Thr Pro Leu Leu Val Ile65 70 75 80Phe Ser Pro Ile Leu Val Pro Ala Leu Ile Thr Val Ala Leu Leu Ile85 90 95Thr Gly Phe Leu Ser Ser Gly Gly Phe Gly Ile Ala Ala Ile Thr Val100 105 110Phe Ser Trp Ile Tyr Lys Tyr Ala Thr Gly Glu His Pro Gln Gly Ser115 120 125Asp Lys Leu Asp Ser Ala Arg Met Lys Leu Gly Ser Lys Ala Gln Asp130 135 140Leu Lys Asp Arg Ala Gln Tyr Tyr Gly Gln Gln His Thr Gly Gly Glu145 150 155 160His Asp Arg Asp Arg Thr Arg Gly Gly Gln His Thr Thr165 170<210>88<211>153<212>PRT<213>Arabidopsis thaliana<400>88Met Ala Pro Phe Pro Leu Ser Leu Ile Phe Gly Lys Lys Lys Arg Arg1 5 10 15Arg Asp Asp Glu Ile Arg Arg Gln Lys Pro Thr Leu Lys Gly Val Met20 25 30Thr Ala Phe Phe Ala Thr Glu Ala Ala Ile Cys Leu Leu Leu Leu Ala35 40 45Gly Ile Ser Leu Thr Gly Thr Ala Val Ala Leu Phe Ala Ser Met Pro50 55 60
Leu Phe Leu Val Phe Ser Pro Val Leu Val Pro Ala Gly Ile Ala Thr65 70 75 80Thr Ile Leu Ala Ser Gly Leu Met Ala Gly Gly Thr Ser Gly Val Ser85 90 95Gly Leu Thr Ile Leu Met Trp Leu Tyr Lys Lys Tyr Thr Gly Arg Asp100 105 110Phe Pro Ile Lys Ile Pro Gly Ala Ala Ala Ala Gly Gly Ala Ala Pro115 120 125Ala Ala Pro Ala Ala Pro Ala Pro Ala Ala Pro Ala Ala Lys Pro Ala130 135 140Ala Lys Pro Ala Ala Lys Pro Gly Ala145 150<210>89<211>173<212>PRT<213>Arabidopsis thaliana<400>89Met Ala Asp Thr Ala Arg Gly Thr His His Asp Ile Ile Gly Arg Asp1 5 10 15Gln Tyr Pro Met Met Gly Arg Asp Arg Asp Gln Tyr Gln Met Ser Gly20 25 30Arg Gly Ser Asp Tyr Ser Lys Ser Arg Gln Ile Ala Lys Ala Ala Thr35 40 45Ala Val Thr Ala Gly Gly Ser Leu Leu Val Leu Ser Ser Leu Thr Leu50 55 60Val Gly Thr Val Ile Ala Leu Thr Val Ala Thr Pro Leu Leu Val Ile65 70 75 80Phe Ser Pro Ile Leu Val Pro Ala Leu Ile Thr Val Ala Leu Leu Ile85 90 95Thr Gly Phe Leu Ser Ser Gly Gly Phe Gly Ile Ala Ala Ile Thr Val100 105 110
Phe Ser Trp Ile Tyr Lys Tyr Ala Thr Gly Glu His Pro Gln Gly Ser115 120 125Asp Lys Leu Asp Ser Ala Arg Met Lys Leu Gly Ser Lys Ala Gln Asp130 135 140Leu Lys Asp Arg Ala Gln Tyr Tyr Gly Gln Gln His Thr Gly Gly Glu145 150 155 160His Asp Arg Asp Arg Thr Arg Gly Gly Gln His Thr Thr165 170<210>90<211>199<212>PRT<213>Arabidopsis thaliana<400>90Met Ala Asp Thr His Arg Val Asp Arg Thr Asp Arg His Phe Gln Phe1 5 10 15Gln Ser Pro Tyr Glu Gly Gly Arg Gly Gln Gly Gln Tyr Glu Gly Asp20 25 30Arg Gly Tyr Gly Gly Gly Gly Tyr Lys Ser Met Met Pro Glu Ser Gly35 40 45Pro Ser Ser Thr Gln Val Leu Ser Leu Leu Ile Gly Val Pro Val Val50 55 60Gly Ser Leu Leu Ala Leu Ala Gly Leu Leu Leu Ala Gly Ser Val Ile65 70 75 80Gly Leu Met Val Ala Leu Pro Leu Phe Leu Leu Phe Ser Pro Val Ile85 90 95Val Pro Ala Ala Leu Thr Ile Gly Leu Ala Met Thr Gly Phe Leu Ala100 105 110Ser Gly Met Phe Gly Leu Thr Gly Leu Ser Ser Ile Ser Trp Val Met115 120 125Asn Tyr Leu Arg Gly Thr Arg Arg Thr Val Pro Glu Gln Leu Glu Tyr130 135 140
Ala Lys Arg Arg Met Ala Asp Ala Val Gly Tyr Ala Gly Gln Lys Gly145 150 155 160Lys Glu Met Gly Gln His Val Gln Asn Lys Ala Gln Asp Val Lys Gln165 170 175Tyr Asp Ile Ser Lys Pro His Asp Thr Thr Thr Lys Gly His Glu Thr180 185 190Gln Gly Arg Thr Thr Ala Ala195<210>91<211>191<212>PRT<213>Arabidopsis thaliana<400>91Met Ala Asn Val Asp Arg Asp Arg Arg Val His Val Asp Arg Thr Asp1 5 10 15Lys Arg Val His Gln Pro Asn Tyr Glu Asp Asp Val Gly Phe Gly Gly20 25 30Tyr Gly Gly Tyr Gly Ala Gly Ser Asp Tyr Lys Ser Arg Gly Pro Ser35 40 45Thr Asn Gln Ile Leu Ala Leu Ile Ala Gly Val Pro Ile Gly Gly Thr50 55 60Leu Leu Thr Leu Ala Gly Leu Thr Leu Ala Gly Ser Val Ile Gly Leu65 70 75 80Leu Val Ser Ile Pro Leu Phe Leu Leu Phe Ser Pro Val Ile Val Pro85 90 95Ala Ala Leu Thr Ile Gly Leu Ala Val Thr Gly Ile Leu Ala Ser Gly100 105 110Leu Phe Gly Leu Thr Gly Leu Ser Ser Val Ser Trp Val Leu Asn Tyr115 120 125Leu Arg Gly Thr Ser Asp Thr Val Pro Glu Gln Leu Asp Tyr Ala Lys130 135 140
Arg Arg Met Ala Asp Ala Val Gly Tyr Ala Gly Met Lys Gly Lys Glu145 150 155 160Met Gly Gln Tyr Val Gln Asp Lys Ala His Glu Ala Arg Glu Thr Glu165 170 175Phe Met Thr Glu Thr His Glu Pro Gly Lys Ala Arg Arg Gly Ser180 185 190<210>92<211>141<212>PRT<213>Arabidopsis thaliana<400>92Met Ala Asp Gln Thr Arg Thr His His Glu Met Ile Ser Arg Asp Ser1 5 10 15Thr Gln Glu Ala His Pro Lys Ala Arg Gln Met Val Lys Ala Ala Thr20 25 30Ala Val Thr Ala Gly Gly Ser Leu Leu Val Leu Ser Gly Leu Thr Leu35 40 45Ala Gly Thr Val Ile Ala Leu Thr Val Ala Thr Pro Leu Leu Val Ile50 55 60Phe Ser Pro Val Leu Val Pro Ala Val Val Thr Val Ala Leu Ile Ile65 70 75 80Thr Gly Phe Leu Ala Ser Gly Gly Phe Gly Ile Ala Ala Ile Thr Ala85 90 95Phe Ser Trp Leu Tyr Arg His Met Thr Gly Ser Gly Ser Asp Lys Ile100 105 110Glu Asn Ala Arg Met Lys Val Gly Ser Arg Val Gln Asp Thr Lys Tyr115 120 125Gly Gln His Asn Ile Gly Val Gln His Gln Gln Val Ser130 135 140<210>93<211>173
<212>PRT<213>Arabidopsis thaliana<400>93Met Ala Asp Thr Ala Arg Gly Thr His His Asp Ile Ile Gly Arg Asp1 5 10 15Gln Tyr Pro Met Met Gly Arg Asp Arg Asp Gln Tyr Gln Met Ser Gly20 25 30Arg Gly Ser Asp Tyr Ser Lys Ser Arg Gln Ile Ala Lys Ala Ala Thr35 40 45Ala Val Thr Ala Gly Gly Ser Leu Leu Val Leu Ser Ser Leu Thr Leu50 55 60Val Gly Thr Val Ile Ala Leu Thr Val Ala Thr Pro Leu Leu Val Ile65 70 75 80Phe Ser Pro Ile Leu Val Pro Ala Leu Ile Thr Val Ala Leu Leu Ile85 90 95Thr Gly Phe Leu Ser Ser Gly Gly Phe Gly Ile Ala Ala Ile Thr Val100 105 110Phe Ser Trp Ile Tyr Lys Tyr Ala Thr Gly Glu His Pro Gln Gly Ser115 120 125Asp Lys Leu Asp Ser Ala Arg Met Lys Leu Gly Ser Lys Ala Gln Asp130 135 140Leu Lys Asp Arg Ala Gln Tyr Tyr Gly Gln Gln His Thr Gly Gly Glul45 150 155 l60His Asp Arg Asp Arg Thr Arg Gly Gly Gln His Thr Thr165 170<210>94<211>199<212>PRT<213>Arabidopsis thaliana<400>94Met Ala Asp Thr His Arg Val Asp Arg Thr Asp Arg His Phe Gln Phe1 5 10 15
Gln Ser Pro Tyr Glu Gly Gly Arg Gly Gln Gly Gln Tyr Glu Gly Asp20 25 30Arg Gly Tyr Gly Gly Gly Gly Tyr Lys Ser Met Met Pro Glu Ser Gly35 40 45Pro Ser Ser Thr Gln Val Leu Ser Leu Leu Ile Gly Val Pro Val Val50 55 60Gly Ser Leu Leu Ala Leu Ala Gly Leu Leu Leu Ala Gly Ser Val Ile65 70 75 80Gly Leu Met Val Ala Leu Pro Leu Phe Leu Leu Phe Ser Pro Val Ile85 90 95Val Pro Ala Gly Leu Thr Ile Gly Leu Ala Met Thr Gly Phe Leu Ala100 105 110Ser Gly Met Phe Gly Leu Thr Gly Leu Ser Ser Ile Ser Trp Val Met115 120 125Asn Tyr Leu Arg Gly Thr Lys Arg Thr Val Pro Glu Gln Leu Glu Tyr130 135 140Ala Lys Arg Arg Met Ala Asp Ala Val Gly Tyr Ala Gly Gln Lys Gly145 150 155 160Lys Glu Met Gly Gln His Val Gln Asn Lys Ala Gln Asp Val Lys Gln165 170 175Tyr Asp Ile Ser Lys Pro His Asp Thr Thr Thr Lys Gly His Glu Thr180 185 190Gln Gly Gly Thr Thr Ala Ala195<210>95<211>191<212>PRT<213>Arabidopsis thaliana<400>95Met Ala Asn Val Asp Arg Asp Arg Arg Val His Val Asp Arg Thr Asp1 5 10 15
Lys Arg Val His Gln Pro Asn Tyr Glu Asp Asp Val Gly Phe Gly Gly20 25 30Tyr Gly Gly Tyr Gly Ala Gly Ser Asp Tyr Lys Ser Arg Gly Pro Ser35 40 45Thr Asn Gln Ile Leu Ala Leu Ile Ala Gly Val Pro Ile Gly Gly Thr50 55 60Leu Leu Thr Leu Ala Gly Leu Thr Leu Ala Gly Ser Val Ile Gly Leu65 70 75 80Leu Val Ser Ile Pro Leu Phe Leu Leu Phe Ser Pro Val Ile Val Pro85 90 95Ala Ala Leu Thr Ile Gly Leu Ala Val Thr Gly Ile Leu Ala Ser Gly100 105 110Leu Phe Gly Leu Thr Gly Leu Ser Ser Val Ser Trp Val Leu Asn Tyr115 120 125Leu Arg Gly Thr Ser Asp Thr Val Pro Glu Gln Leu Asp Tyr Ala Lys130 135 140Arg Arg Met Ala Asp Ala Val Gly Tyr Ala Gly Met Lys Gly Lys Glu145 150 155 160Met Gly Gln Tyr Val Gln Asp Lys Ala His Glu Ala Arg Glu Thr Glu165 170 175Phe Met Thr Glu Thr His Glu Pro Gly Lys Ala Arg Arg Gly Ser180 185 190<210>96<211>153<212>PRT<213>Arabidopsis thaliana<400>96Met Ala Pro Phe Pro Leu Ser Leu Ile Phe Gly Lys Lys Lys Arg Arg1 5 10 15Arg Asp Asp Glu Ile Arg Arg Gln Lys Pro Thr Leu Lys Gly Val Met20 25 30
Thr Ala Phe Phe Ala Thr Glu Ala Ala Ile Cys Leu Leu Leu Leu Ala35 40 45Gly Ile Ser Leu Thr Gly Thr Ala Val Ala Leu Phe Ala Ser Met Pro50 55 60Leu Phe Leu Val Phe Ser Pro Val Leu Val Pro Ala Gly Ile Ala Thr65 70 75 80Thr Ile Leu Ala Ser Gly Leu Met Ala Gly Gly Thr Ser Gly Val Ser85 90 95Gly Leu Thr Ile Leu Met Trp Leu Tyr Lys Lys Tyr Thr Gly Arg Asp100 105 110Phe Pro Ile Lys Ile Pro Gly Ala Ala Ala Ala Gly Gly Ala Ala Pro115 120 125Ala Ala Pro Ala Ala Pro Ala Pro Ala Ala Pro Ala Ala Lys Pro Ala130 135 140Ala Lys Pro Ala Ala Lys Pro Gly Ala145 150<210>97<211>175<212>PRT<213>Brassica napus<400>97Arg Arg Asp Gln Tyr Pro Arg Asp Arg Asp Gln Tyr Ser Met Ile Gly1 5 10 15Arg Asp Arg Asp Lys Tyr Ser Met Ile Gly Arg Asp Arg Asp Gln Tyr20 25 30Asn Met Tyr Gly Arg Asp Tyr Ser Lys Ser Arg Gln Ile Ala Lys Ala35 40 45Val Thr Ala Val Thr Ala Gly Gly Ser Leu Leu Val Leu Ser Ser Leu50 55 60Thr Leu Val Gly Thr Val Ile Ala Leu Thr Val Ala Thr Pro Leu Leu65 70 75 80
Val Ile Phe Ser Pro Ile Leu Val Pro Ala Leu Ile Thr Val Ala Leu85 90 95Leu Ile Thr Gly Phe Leu Ser Ser Gly Gly Phe Gly Ile Ala Ala Ile100 105 110Thr Val Phe Ser Trp Ile Tyr Lys Tyr Ala Thr Gly Glu His Pro Gln115 120 125Gly Ser Asp Lys Leu Asp Ser Ala Arg Met Lys Leu Gly Gly Lys Val130 135 140Gln Asp Met Lys Asp Arg Ala Gln Tyr Tyr Gly Gln Gln Gln Thr Gly145 150 155 160Gly Glu Asp Asp Arg Asp Arg Thr Arg Gly Thr Gln His Thr Thr165 170 175<210>98<211>216<212>PRT<213>Brassica oleracea<400>98Arg Phe Phe Arg Met Phe Ser Phe Ile Phe Pro Leu Leu Asn Val Ile1 5 10 15Lys Leu Ile Ile Ala Ser Val Thr Ser Leu Val Cys Leu Ala Phe Ser20 25 30Cys Val Thr Leu Gly Gly Ser Ala Val Ala Leu Ile Val Ser Thr Pro35 40 45Leu Phe Ile Ile Phe Ser Pro Ile Leu Val Pro Ala Thr Ile Ala Thr50 55 60Thr Leu Leu Ala Ser Gly Leu Met Ala Gly Thr Thr Leu Gly Leu Thr65 70 75 80Gly Ile Gly Leu Ile Thr Gly Leu Val Arg Thr Ala Gly Gly Val Thr85 90 95Leu Ala Glu Ser Pro Ile Arg Arg Ile Ile Ile Asn Arg Ile Lys Ala100 105 110
Arg Leu Gly Gly Gly Gly Gly Ser Arg Leu Ala Met Leu Lys Lys Ile115 120 125Leu Gly Leu Ile Lys Lys Leu Arg Gly Met Ser Ser Gly Gly Ala Ala130 135 140Pro Ala Leu Lys Gln His Gln Gln Leu Arg Pro Arg Met Glu Leu His145 150 155 160Pro Arg His Leu His Arg Pro Asn Lys Glu Arg Trp Phe Met Leu Phe165 170 175Gln Tyr Val Ala His Lys Asn Cys Val Ile Ile Asn Leu Arg Ile Tyr180 185 190Asp Ser Glu Thr Lys Lys Lys Ile Ala Leu Leu Leu Ser Phe Ile Gln195 200 205Tyr Ser Phe Lau Cys Asn Asn Val210 215<210>99<211>195<212>PRT<213>Brassica napus<400>99Met Thr Asp Thr Ala Arg Thr His His Asp Ile Thr Ser Arg Asp Gln1 5 10 15Tyr Pro Arg Asp Arg Asp Gln Tyr Ser Met Ile Gly Arg Asp Arg Asp20 25 30Gln Tyr Ser Met Met Gly Arg Asp Arg Asp Gln Tyr Asn Met Tyr Gly35 40 45Arg Asp Tyr Ser Lys Ser Arg Gln Ile Ala Lys Ala Val Thr Ala Val50 55 60Thr Ala Gly Gly Ser Leu Leu Val Leu Ser Ser Leu Thr Leu Val Gly65 70 75 80Thr Val Ile Ala Leu Thr Val Ala Thr Pro Leu Leu Val Ile Phe Ser85 90 95
Pro Ile Leu Val Pro Ala Leu Ile Thr Val Ala Met Leu Ile Thr Gly100 105 110Phe Leu Ser Ser Gly Gly Phe Gly Ile Ala Ala Ile Thr Val Phe Ser115 120 125Trp Ile Tyr Lys Tyr Ala Thr Gly Glu His Pro Gln Gly Ser Asp Lys130 135 140Leu Asp Ser Ala Arg Met Lys Leu Gly Ser Lys Ala Gln Asp Leu Lys145 150 155 160Asp Arg Ala Gln Tyr Tyr Gly Gln Gln His Thr Gly Gly Tyr Gly Gln165 170 175Gln His Thr Gly Gly Glu His Asp Arg Asp Arg Thr Arg Gly Thr Gln180 185 190His Thr Thr195<210>100<211>183<212>PRT<213>Brassica napus<400>100Pro Ala Arg Thr His His Asp Ile Thr Thr Arg Asp Gln Tyr Pro Leu15 10 15Ile Ser Arg Asp Arg Asp Gln Tyr Gly Met Ile Gly Arg Asp Gln Tyr20 25 30Asn Met Ser Gly Gln Asn Tyr Ser Lys Ser Arg Gln Ile Ala Lys Ala35 40 45Thr Thr Ala Val Thr Ala Gly Asp Ser Leu Leu Val Leu Ser Ser Leu50 55 60Thr Leu Val Gly Thr Val Ile Ala Leu Ile Val Ala Thr Pro Leu Leu65 70 75 80Val Ile Phe Ser Pro Ile Leu Val Pro Ala Leu Ile Thr Val Ala Leu85 90 95
Leu Ile Thr Gly Phe Leu Ser Ser Gly Ala Phe Gly Ile Ala Ala Ile100 105 110Thr Val Phe Ser Trp Ile Tyr Lys Tyr Ala Thr Gly Glu His Pro Gln115 120 125Gly Ser Asp Lys Leu Asp Ser Ala Arg Met Lys Leu Gly Ser Lys Ala130 135 140Gln Asp Met Lys Asp Arg Ala Tyr Tyr Tyr Gly Gln Gln His Thr Gly145 150 155 160Glu Glu His Asp Arg Asp Arg Asp His Arg Thr Asp Arg Asp Arg Thr165 170 175Arg Gly Thr Gln His Thr Thr180<210>101<211>183<212>PRT<213>Brassica napus<400>101Pro Ala Arg Thr His His Asp Ile Thr Thr Arg Asp Gln Tyr Pro Leu1 5 10 15Ile Ser Arg Asp Arg Asp Gln Tyr Gly Met Ile Gly Arg Asp Gln Tyr20 25 30Asn Met Ser Gly Gln Asn Tyr Ser Lys Ser Arg Gln Ile Ala Lys Ala35 40 45Thr Thr Ala Val Thr Ala Gly Asp Ser Leu Leu Val Leu Ser Ser Leu50 55 60Thr Leu Val Gly Thr Val Ile Ala Leu Ile Val Ala Thr Pro Leu Leu65 70 75 80Val Ile Phe Ser Pro Ile Leu Val Pro Ala Leu Ile Thr Val Ala Leu85 90 95Leu Ile Thr Gly Phe Leu Ser Ser Gly Ala Phe GlyIle Ala Ala Ile100 105 110
Thr Val Phe Ser Trp Ile Tyr Lys Tyr Ala Thr Gly Glu His Pro Gln115 120 125Gly Ser Asp Lys Leu Asp Ser Ala Arg Met Lys Leu Gly Ser Lys Ala130 135 l40Gln Asp Met Lys Asp Arg Ala Tyr Tyr Tyr Gly Gln Gln His Thr Gly145 150 155 160Glu Glu His Asp Arg Asp Arg Asp His Arg Thr Asp Arg Asp Arg Thr165 170 175Arg Gly Thr Gln His Thr Thr180<210>102<211>195<212>PRT<213>Brassica napus<400>102Met Thr Asp Thr Ala Arg Thr His His Asp Ile Thr Ser Arg Asp Gln1 5 10 15Tyr Pro Arg Asp Arg Asp Gln Tyr Ser Met Ile Gly Arg Asp Arg Asp20 25 30Gln Tyr Ser Met Met Gly Arg Asp Arg Asp Gln Tyr Asn Met Tyr Gly35 40 45Arg Asp Tyr Ser Lys Ser Arg Gln Ile Ala Lys Ala Val Thr Ala Val50 55 60Thr Ala Gly Gly Ser Leu Leu Val Leu Ser Ser Leu Thr Leu Val Gly65 70 75 80Thr Val Ile Ala Leu Thr Val Ala Thr Pro Leu Leu Val Ile Phe Ser85 90 95Pro Ile Leu Val Pro Ala Leu Ile Thr Val Ala Met Leu Ile Thr Gly100 105 110Phe Leu Ser Ser Gly Gly Phe Gly Ile Ala Ala Ile Thr Val Phe Ser115 120 125
Trp Ile Tyr Lys Tyr Ala Thr Gly Glu His Pro Gln Gly Ser Asp Lys130 135 140Leu Asp Ser Ala Arg Met Lys Leu Gly Ser Lys Ala Gln Asp Leu Lys145 150 155 160Asp Arg Ala Gln Tyr Tyr Gly Gln Gln His Thr Gly Gly Tyr Gly Gln165 170 175Gln His Thr Gly Gly Glu His Asp Arg Asp Arg Thr Arg Gly Thr Gln180 185 190His Thr Thr195<210>103<211>175<212>PRT<213>Brassica napus<400>103Arg Arg Asp Gln Tyr Pro Arg Asp Arg Asp Gln Tyr Ser Met Ile Gly1 5 10 15Arg Asp Arg Asp Lys Tyr Ser Met Ile Gly Arg Asp Arg Asp Gln Tyr20 25 30Asn Met Tyr Gly Arg Asp Tyr Ser Lys Ser Arg Gln Ile Ala Lys Ala35 40 45Val Thr Ala Val Thr Ala Gly Gly Ser Leu Leu Val Leu Ser Ser Leu50 55 60Thr Leu Val Gly Thr Val Ile Ala Leu Thr Val Ala Thr Pro Leu Leu65 70 75 80Val Ile Phe Ser Pro Ile Leu Val Pro Ala Leu Ile Thr Val Ala Leu85 90 95Leu Ile Thr Gly Phe Leu Ser Ser Gly Gly Phe Gly Ile Ala Ala Ile100 105 110Thr Val Phe Ser Trp Ile Tyr Lys Tyr Ala Thr Gly Glu His Pro Gln115 120 125
Gly Ser Asp Lys Leu Asp Ser Ala Arg Met Lys Leu Gly Gly Lys Val130 135 140Gln Asp Met Lys Asp Arg Ala Gln Tyr Tyr Gly Gln Gln Gln Thr Gly145 150 155 160Gly Glu Asp Asp Arg Asp Arg Thr Arg Gly Thr Gln His Thr Thr165 170 175<210>104<211>195<212>PRT<213>Brassica napus<400>104Met Thr Asp Thr Ala Arg Thr His His Asp Ile Thr Ser Arg Asp Gln1 5 10 15Tyr Pro Arg Asp Arg Asp Gln Tyr Ser Met Ile Gly Arg Asp Arg Asp20 25 30Gln Tyr Ser Met Met Gly Arg Asp Arg Asp Gln Tyr Asn Met Tyr Gly35 40 45Arg Asp Tyr Ser Lys Ser Arg Gln Ile Ala Lys Ala Val Thr Ala Val50 55 60Thr Ala Gly Gly Ser Leu Leu Val Leu Ser Ser Leu Thr Lau Val Gly65 70 75 80Thr Val Ile Ala Leu Thr Val Ala Thr Pro Leu Leu Val Ile Phe Ser85 90 95Pro Ile Leu Val Pro Ala Leu Ile Thr Val Ala Met Leu Ile Thr Gly100 105 110Phe Leu Ser Ser Gly Gly Phe Gly Ile Ala Ala Ile Thr Val Phe Ser115 120 125Trp Ile Tyr Lys Tyr Ala Thr Gly Glu His Pro Gln Gly Ser Asp Lys130 135 140Leu Asp Ser Ala Arg Met Lys Leu Gly Ser Lys Ala Gln Asp Leu Lys145 150 155 160
Asp Arg Ala Gln Tyr Tyr Gly Gln Gln His Thr Gly Gly Tyr Gly Gln165 170 175Gln His Thr Gly Gly Glu His Asp Arg Asp Arg Thr Arg Gly Thr Gln180 185 190His Thr Thr195<210>105<211>165<212>PRT<213>Brassica napus<400>105Met Gly Ile Leu Arg Lys Lys Lys His Glu Arg Lys Pro Ser Phe Lys1 5 10 15Ser Val Leu Thr Ala Ile Leu Ala Thr His Ala Ala Thr Phe Leu Leu20 25 30Leu Ile Ala Gly Val Ser Leu Ala Gly Thr Ala Ala Ala Phe Ile Ala35 40 45Thr Met Pro Leu Phe Val Val Phe Ser Pro Ile Leu Val Pro Ala Gly50 55 60Ile Thr Thr Gly Leu Leu Thr Thr Gly Leu Ala Ala Ala Gly Gly Ala65 70 75 80Gly Ala Thr Ala Val Thr Ile Ile Leu Trp Leu Tyr Lys Arg Ala Thr85 90 95Gly Lys Ala Pro Pro Lys Val Leu Glu Lys Val Leu Lys Lys Ile Ile100 105 110Pro Gly Ala Ala Ala Ala Pro Ala Ala Ala Pro Gly Ala Ala Pro Ala115 120 125Ala Ala Pro Ala Ala Ala Pro Ala Val Ala Pro Ala Ala Ala Pro Ala130 135 140Ala Ala Pro Ala Pro Lys Pro Ala Ala Pro Pro Ala Pro Lys Pro Ala145 150 155 160
Ala Ala Pro Ser Ile165<210>106<211>375<212>PRT<213>Brassica napus<400>106Met Lys Glu Glu Ile Gln Asn Glu Thr Ala Gln Thr Gln Leu Gln Arg1 5 10 15Glu Gly Arg Met Phe Ser Phe Leu Phe Pro Val Ile Glu Val Ile Lys20 25 30Val Val Met Ala Ser Val Ala Ser Val Val Phe Leu Gly Phe Gly Gly35 40 45Val Thr Leu Ala Cys Ser Ala Val Ala Leu Ala Val Ser Thr Pro Leu50 55 60Phe Ile Ile Phe Ser Pro Ile Leu Val Pro Ala Thr Ile Ala Thr Thr65 70 75 80Leu Leu Ala Thr Gly Leu Gly Ala Gly Thr Thr Leu Gly Val Thr Gly85 90 95Met Gly Leu Leu Met Arg Leu Ile Lys His Pro Gly Lys Glu Gly Ala100 105 110Ala Ser Ala Pro Ala Ala Gln Pro Ser Phe Leu Ser Leu Leu Glu Met115 120 125Pro Asn Phe Ile Lys Ser Lys Met Leu Glu Arg Leu Ile His Ile Pro130 135 140Gly Val Gly Lys Lys Ser Glu Gly Arg Gly Glu Ser Lys Gly Lys Lys145 150 155 160Gly Lys Lys Gly Lys Ser Glu His Gly Arg Gly Lys His Glu Gly Glu165 170 175Gly Lys Ser Lys Gly Arg Lys Gly His Arg Met Gly Val Asn Pro Glu180 185 190
Asn Asn Pro Pro Pro Ala Gly Ala Pro Pro Thr Gly Ser Pro Pro Ala195 200 205Ala Pro Ala Ala Pro Glu Ala Pro Ala Ala Pro Ala Ala Pro Ala Ala210 215 220Pro Ala Ala Pro Ala Ala Pro Ala Ala Pro Ala Ala Pro Glu Asp Pro225 230 235 240Ala Ala Pro Ala Ala Pro Glu Ala Pro Ala Thr Pro Ala Ala Pro Pro245 250 255Ala Pro Ala Ala Ala Pro Ala Pro Ala Ala Pro Ala Ala Pro Pro Ala260 265 270Pro Ala Ala Pro Pro Arg Pro Pro Ser Phe Leu Ser Leu Leu Glu Met275 280 285Pro Ser Phe Ile Lys Ser Lys Leu Ile Glu Ala Leu Ile Asn Ile Pro290 295 300Gly Phe Gly Lys Lys Ser Asn Asp Arg Gly Lys Ser Lys Gly Gly Lys305 310 315 320Lys Ser Lys Gly Lys Gly Lys Ser Asn Gly Arg Gly Lys His Glu Gly325 330 335Glu Gly Lys Ser Lys Ser Arg Lys Ser Lys Ser Arg Gly Lys Asp Lys340 345 350Glu Lys Ser Lys Gly Lys Gly Ile Phe Gly Arg Ser Ser Arg Lys Gly355 360 365Ser Ser Asp Asp Glu Ser Ser370 375<210>107<211>168<212>PRT<213>Daucus carota<220>
<221>misc_feature<222>(55)..(55)<223>Xaa can be any naturally occurring amino acid
<220>
<221>misc_feature<222>(139)..(139)<223>Xaa can be any naturally occurring amino acid<220>
<221>misc_feature<222>(159)..(159)<223>Xaa can be any naturally occurring amino acid<400>107Asn Lys Phe Thr Leu Ser Asn Leu Ile Ser Val Asp Phe Met Ala Met1 5 10 15Tyr Gln Ser Pro Gln Phe Thr Arg His His Asp Ala Leu Gln Pro Ala20 25 30Ala Leu Asn Ser Ser Gly Gln Gly His His Ser Ser His His Arg Arg35 40 45Ser Val Met Leu Leu Ser Xaa Leu Thr Leu Val Ala Thr Val Ile Gly50 55 60Leu Val Ile Ala Thr Pro Val Met Val Ile Phe Ser Pro Val Leu Val65 70 75 80Pro Ala Gly Leu Pro Ala Ala Pro Ala Arg Arg Val Ser His Gly Gly85 90 95Gly Ala Gly Gly His Arg Ala Phe Val Leu Phe Trp Met Tyr Arg Tyr100 105 110Thr Ala Gly Lys His Pro Ile Gly Ala Asn Gln Leu Asp Phe Ala Ala115 120 125Thr Arg Leu Arg Met Arg Lys Glu Lys Gly Xaa Ile Trp Gly Met Ser130 135 140Arg Phe Arg Leu Phe Arg Gly Val Glu Glu Val Val Arg Arg Xaa Gly145 150 155 160Asn Asp Glu Gly Phe Leu Ala Val165<210>108<211>168
<212>PRT<213>Daucus carota<220>
<221>misc_feature<222>(55)..(55)<223>Xaa can be any naturally occurring amino acid<220>
<221>misc_feature<222>(139)..(139)<223>Xaa can be any naturally occurring amino acid<220>
<221>misc_feature<222>(159)..(159)<223>Xaa can be any naturally occurring amino acid<400>108Asn Lys Phe Thr Leu Ser Asn Leu Ile Ser Val Asp Phe Met Ala Met1 5 10 15Tyr Gln Ser Pro Gln Phe Thr Arg His His Asp Ala Leu Gln Pro Ala20 25 30Ala Leu Asn Ser Ser Gly Gln Gly His His Ser Ser His His Arg Arg35 40 45Ser Val Met Leu Leu Ser Xaa Leu Thr Leu Val Ala Thr Val Ile Gly50 55 60Leu Val Ile Ala Thr Pro Val Met Val Ile Phe Ser Pro Val Leu Val65 70 75 80Pro Ala Gly Leu Pro Ala Ala Pro Ala Arg Arg Val Ser His Gly Gly85 90 95Gly Ala Gly Gly His Arg Ala Phe Val Leu Phe Trp Met Tyr Arg Tyr100 105 110Thr Ala Gly Lys His Pro Ile Gly Ala Asn Gln Leu Asp Phe Ala Ala115 120 125Thr Arg Leu Arg Met Arg Lys Glu Lys Gly Xaa Ile Trp Gly Met Ser130 135 140Arg Phe Arg Leu Phe Arg Gly Val Glu Glu Val Val Arg Arg Xaa Gly145 150 155 160
Asn Asp Glu Gly Phe Leu Ala Val165<210>109<211>187<212>PRT<213>Zea mays<400>109Met Ala Asp Arg Asp Arg Ser Gly Ile Tyr Gly Gly Ala His Ala Thr1 5 10 15Tyr Gly Gln Gln Gln Gln Gln Gly Gly Gly Gly Arg Pro Met Gly Glu20 25 30Gln Val Lys Lys Gly Met Leu His Asp Lys Gly Pro Thr Ala Ser Gln35 40 45Ala Leu Thr Val Ala Thr Leu Phe Pro Leu Gly Gly Leu Leu Leu Val50 55 60Leu Ser Gly Leu Ala Leu Thr Ala Ser Val Val Gly Leu Ala Val Ala65 70 75 80Thr Pro Val Phe Leu Ile Phe Ser Pro Val Leu Val Pro Ala Ala Leu85 90 95Leu Ile Gly Thr Ala Val Met Gly Phe Leu Thr Ser Gly Ala Leu Gly100 105 110Leu Gly Gly Leu Ser Ser Leu Thr Cys Leu Ala Asn Thr Ala Arg Gln115 120 125Ala Phe Gln Arg Thr Pro Asp Tyr Val Glu Glu Ala Arg Arg Arg Met130 135 140Ala Glu Ala Ala Ala Gln Ala Gly His Lys Thr Ala Gln Ala Gly Gln145 150 155 160Ala Ile Gln Gly Arg Ala Gln Glu Ala Gly Thr Gly Gly Gly Ala Gly165 170 175Ala Gly Ala Gly Gly Gly Gly Arg Ala Ser Ser180 185
<210>110<211>187<212>PRT<213>Zea mays<400>110Met Ala Asp Arg Asp Arg Ser Gly Ile Tyr Gly Gly Ala His Ala Thr15 10 15Tyr Gly Gln Gln Gln Gln Gln Gly Gly Gly Gly Arg Pro Met Gly Glu20 25 30Gln Val Lys Lys Gly Met Leu His Asp Lys Gly Pro Thr Ala Ser Gln35 40 45Ala Leu Thr Val Ala Thr Leu Phe Pro Leu Gly Gly Leu Leu Leu Val50 55 60Leu Ser Gly Leu Ala Leu Thr Ala Ser Val Val Gly Leu Ala Val Ala65 70 75 80Thr Pro Val Phe Leu Ile Phe Ser Pro Val Leu Val Pro Ala Ala Leu85 90 95Leu Ile Gly Thr Ala Val Met Gly Phe Leu Thr Ser Gly Ala Leu Gly100 105 110Leu Gly Gly Leu Ser Ser Leu Thr Cys Leu Ala Asn Thr Ala Arg Gln115 120 125Ala Phe Gln Arg Thr Pro Asp Tyr Val Glu Glu Ala Arg Arg Arg Met130 135 140Ala Glu Ala Ala Ala Gln Ala Gly His Lys Thr Ala Gln Ala Gly Gln145 150 155 160Ala Ile Gln Gly Arg Ala Gln Glu Ala Gly Thr Gly Gly Gly Ala Gly165 170 175Ala Gly Ala Gly Gly Gly Gly Arg Ala Ser Ser180 185<210>111<211>156
<212>PRT<213>Zea mays<400>111Met Ala Asp His His Arg Gly Ala Thr Gly Gly Gly Gly Gly Tyr Gly1 5 10 15Asp Leu Gln Arg Gly Gly Gly Met His Gly Glu Ala Gln Gln Gln Gln20 25 30Lys Gln Gly Ala Met Met Thr Ala Leu Lys Ala Ala Thr Ala Ala Thr35 40 45Phe Gly Gly Ser Met Leu Val Leu Ser Gly Leu Ile Leu Ala Gly Thr50 55 60Val Ile Ala Leu Thr Val Ala Thr Pro Val Leu Val Ile Phe Ser Pro65 70 75 80Val Leu Val Pro Ala Ala Ile Ala Leu Ala Leu Met Ala Ala Gly Phe85 90 95Val Thr Ser Gly Gly Leu Gly Val Ala Ala Leu Ser Val Phe Ser Trp100 105 110Met Tyr Lys Tyr Leu Thr Gly Lys His Pro Pro Ala Ala Asp Gln Leu115 120 125Asp His Ala Lys Ala Arg Leu Ala Ser Lys Ala Arg Asp Val Lys Asp130 135 140Ala Ala Gln His Arg Ile Asp Gln Ala Gln Gly Ser145 150 155<210>112<211>175<212>PRT<213>Zea mays<400>112Met Ala Asp Arg Asp Arg Ser Gly Ile Tyr Gly Gly Gly Ala Tyr Gly1 5 10 15Gln Gln Gln Gly Arg Pro Pro Met Gly Glu Gln Val Lys Gly Met Ile20 25 30
His Asp Lys Gly Pro Thr Ala Ser Gln Ala Leu Thr Val Ala Thr Leu35 40 45Phe Pro Leu Gly Gly Leu Leu Leu Val Leu Ser Gly Leu Ala Leu Ala50 55 60Ala Ser Thr Val Gly Leu Ala Val Ala Thr Pro Val Phe Leu Leu Phe65 70 75 80Ser Pro Val Leu Val Pro Ala Ala Leu Leu Ile Gly Thr Ala Val Ala85 90 95Gly Phe Leu Thr Ser Gly Ala Leu Gly Leu Gly Gly Leu Ser Ser Leu100 105 110Thr Cys Leu Ala Asn Thr Ala Arg Gln Ala Phe Gln Arg Thr Pro Asp115 120 125Tyr Val Glu Glu Ala Arg Arg Arg Met Ala Glu Ala Ala Ala His Ala130 135 140Gly His Lys Thr Ala Gln Ala Gly His Gly Ile Gln Ser Lys Ala Gln145 150 155 160Glu Ala Gly Ala Gly Thr Gly Ala Gly Gly Gly Arg Thr Ser Ser165 170 175<210>113<211>156<212>PRT<213>Zea mays<400>113Met A1a Asp His His Arg Gly Ala Thr Gly Gly Gly Gly Gly Tyr Gly1 5 10 15Asp Leu Gln Arg Gly Gly Gly Met His Gly Glu Ala Gln Gln Gln Gln20 25 30Lys Gln Gly Ala Met Met Thr Ala Leu Lys Ala Ala Thr Ala Ala Thr35 40 45Phe Gly Gly Ser Met Leu Val Leu Ser Gly Leu Ile Leu Ala Gly Thr50 55 60
Val Ile Ala Leu Thr Val Ala Thr Pro Val Leu Val Ile Phe Ser Pro65 70 75 80Val Leu Val Pro Ala Ala Ile Ala Leu Ala Leu Met Ala Ala Gly Phe85 90 95Val Thr Ser Gly Gly Leu Gly Val Ala Ala Leu Ser Val Phe Ser Trp100 105 110Met Tyr Lys Tyr Leu Thr Gly Lys His Pro Pro Ala Ala Asp Gln Leu115 120 125Asp His Ala Lys Ala Arg Leu Ala Ser Lys Ala Arg Asp Val Lys Asp130 135 140Ala Ala Gln His Arg Ile Asp Gln Ala Gln Gly Ser145 150 155<210>114<211>187<212>PRT<213>Zea mays<400>114Met Ala Asp Arg Asp Arg Ser Gly Ile Tyr Gly Gly Ala His Ala Thr1 5 10 15Tyr Gly Gln Gln Gln Gln Gln Gly Gly Gly Gly Arg Pro Met Gly Glu20 25 30Gln Val Lys Lys Gly Met Leu His Asp Lys Gly Pro Thr Ala Ser Gln35 40 45Ala Leu Thr Val Ala Thr Leu Phe Pro Leu Gly Gly Leu Leu Leu Val50 55 60Leu Ser Gly Leu Ala Leu Thr Ala Ser Val Val Gly Leu Ala Val Ala65 70 75 80Thr Pro Val Phe Leu Ile Phe Ser Pro Val Leu Val Pro Ala Ala Leu85 90 95Leu Ile Gly Thr Ala Val Met Gly Phe Leu Thr Ser Gly Ala Leu Gly100 105 110
Leu Gly Gly Leu Ser Ser Leu Thr Cys Leu Ala Asn Thr Ala Arg Gln115 120 125Ala Phe Gln Arg Thr Pro Asp Tyr Val Glu Glu Ala Arg Arg Arg Met130 135 140Ala Glu Ala Ala Ala Gln Ala Gly His Lys Thr Ala Gln Ala Gly Gln145 150 155 160Ala Ile Gln Gly Arg Ala Gln Glu Ala Gly Thr Gly Gly Gly Ala Gly165 170 175Ala Gly Ala Gly Gly Gly Gly Arg Ala Ser Ser180 185<210>115<211>156<212>PRT<213>Zea mays<400>115Met Ala Asp His His Arg Gly Ala Thr Gly Gly Gly Gly Gly Tyr Gly1 5 10 15Asp Leu Gln Arg Gly Gly Gly Met His Gly Glu Ala Gln Gln Gln Gln20 25 30Lys Gln Gly Ala Met Met Thr Ala Leu Lys Ala Ala Thr Ala Ala Thr35 40 45Phe Gly Gly Ser Met Leu Val Leu Ser Gly Leu Ile Leu Ala Gly Thr50 55 60Val Ile Ala Leu Thr Val Ala Thr Pro Val Leu Val Ile Phe Ser Pro65 70 75 80Val Leu Val Pro Ala Ala Ile Ala Leu Ala Leu Met Ala Ala Gly Phe85 90 95Val Thr Ser Gly Gly Leu Gly Val Ala Ala Leu Ser Val Phe Ser Trp100 105 110Met Tyr Lys Tyr Leu Thr Gly Lys His Pro Pro Ala Ala Asp Gln Leu115 120 125
Asp His Ala Lys Ala Arg Leu Ala Ser Lys Ala Arg Asp Val Lys Asp130 135 140Ala Ala Gln His Arg Ile Asp Gln Ala Gln Gly Ser145 150 155<210>116<211>175<212>PRT<213>Zea mays<400>116Met Ala Asp Arg Asp Arg Ser Gly Ile Tyr Gly Gly Gly Ala Tyr Gly1 5 10 15Gln Gln Gln Gly Arg Pro Pro Met Gly Glu Gln Val Lys Gly Met Ile20 25 30His Asp Lys Gly Pro Thr Ala Ser Gln Ala Leu Thr Val Ala Thr Leu35 40 45Phe Pro Leu Gly Gly Leu Leu Leu Val Leu Ser Gly Leu Ala Leu Ala50 55 60Ala Ser Thr Val Gly Leu Ala Val Ala Thr Pro Val Phe Leu Leu Phe65 70 75 80Ser Pro Val Leu Val Pro Ala Ala Leu Leu Ile Gly Thr Ala Val Ala85 90 95Gly Phe Leu Thr Ser Gly Ala Leu Gly Leu Gly Gly Leu Ser Ser Leu100 105 110Thr Cys Leu Ala Asn Thr Ala Arg Gln Ala Phe Gln Arg Thr Pro Asp115 120 125Tyr Val Glu Glu Ala Arg Arg Arg Met Ala Glu Ala Ala Ala His Ala130 135 140Gly His Lys Thr Ala Gln Ala Gly His Gly Ile Gln Ser Lys Ala Gln145 150 155 160Glu Ala Gly Ala Gly Thr Gly Ala Gly Gly Gly Arg Thr Ser Ser165 170 175
<210>117<211>217<212>PRT<213>Oryza sativa<400>117Met Ala Leu Val Leu Phe Ala Ser Ser Ser Ser Cys Lys Arg Pro Val5 10 15Thr His Asn Ile Leu Cys Gly Thr Arg Ala Lys Gly Ser Pro Ala Ala20 25 30Ala Ala Ala Val Gly Ala Ala Thr Glu Leu Gln Lys His Val Ala Phe35 40 45Phe Asp Ser Asn His Asp Gly Ile Ile Ser Phe Ser Glu Thr Tyr Glu50 55 60Gly Phe Arg Ala Leu Gly Phe Gly Val Val Thr Ser Arg Phe Ser Ala65 70 75 80Thr Val Ile Asn Gly Ala Leu Gly Thr Lys Thr Arg Pro Glu Asn Ala85 90 95Thr Ala Ser Arg Phe Ser Ile Tyr Ile Glu Asn Ile His Lys Gly Val100 105 110His Gly Ser Asp Thr Gly Ala Phe Asp Ser Glu Gly Arg Phe Val Asn115 120 125Glu Lys Phe Asp Glu Ile Phe Thr Lys His Ala Lys Thr Val Pro Asp130 135 140Gly Leu Thr Ala Ala Glu Leu Asp Glu Met Leu Arg Ala Asn Arg Glu145 150 155 160Pro Lys Asp Tyr Lys Gly Trp Val Gly Ala Ser Thr Glu Trp Glu Thr165 70 175Thr Phe Lys Leu Gly Lys Asp Lys Asp Gly Phe Leu Arg Lys Asp Thr180 185 190Val Arg Thr Val Tyr Asp Gly Ser Phe Phe Ser Lys Val Ala Ser Lys195 200 205
Lys Lys Gly Pro Ser Ala Asn Gln Ala210 215<210>118<211>217<212>PRT<213>Oryza sativa<400>118Met Ala Leu Val Leu Phe Ala Ser Ser Ser Ser Cys Lys Arg Pro Val1 5 10 15Thr His Asn Ile Leu Cys Gly Thr Arg Ala Lys Gly Ser Pro Ala Ala20 25 30Ala Ala Ala Val Gly Ala Ala Thr Glu Leu Gln Lys His Val Ala Phe35 40 45Phe Asp Ser Asn His Asp Gly Ile Ile Ser Phe Ser Glu Thr Tyr Glu50 55 60Gly Phe Arg Ala Leu Gly Phe Gly Val Val Thr Ser Arg Phe Ser Ala65 70 75 80Thr Val Ile Asn Gly Ala Leu Gly Thr Lys Thr Arg Pro Glu Asn Ala85 90 95Thr Ala Ser Arg Phe Ser Ile Tyr Ile Glu Asn Ile His Lys Gly Val100 105 110His Gly Ser Asp Thr Gly Ala Phe Asp Ser Glu Gly Arg Phe Val Asn115 120 125Glu Lys Phe Asp Glu Ile Phe Thr Lys His Ala Lys Thr Val Pro Asp130 135 140Gly Leu Thr Ala Ala Glu Leu Asp Glu Met Leu Arg Ala Asn Arg Glu145 150 155 160Pro Lys Asp Tyr Lys Gly Trp Val Gly Ala Ser Thr Glu Trp Glu Thr165 170 175Thr Phe Lys Leu Gly Lys Asp Lys Asp Gly Phe Leu Arg Lys Asp Thr180 185 190
Val Arg Thr Val Tyr Asp Gly Ser Phe Phe Ser Lys Val Ala Ser Lys195 200 205Lys Lys Gly Pro Ser Ala Asn Gln Ala210 215<210>119<211>174<212>PRT<213>Arabidopsis thaliana<400>119Met Phe Phe Cys Phe Cys Phe Cys Glu Ser Lys Lys Gly Leu Cys Met1 5 10 15Glu Thr Tyr Leu Trp Asp Tyr Val Val Tyr Val Gly Gly Lys Leu Asp20 25 30Lys Glu Lys Met Thr Ala Leu Glu Lys His Val Ser Phe Phe Asp Arg35 40 45Asn Lys Asp Gly Thr Val Tyr Pro Trp Glu Thr Tyr Gln Gly Phe Arg50 55 60Ala Leu Gly Thr Gly Arg Leu Leu Ala Ala Phe Val Ala Ile Phe Ile65 70 75 80Asn Met Gly Leu Ser Lys Lys Thr Arg Pro Gly Lys Gly Phe Ser Pro85 90 95Leu Phe Pro Ile Asp Val Lys Asn Ser His Leu Cys Met His Gly Ser100 105 110Asp Thr Asp Val Tyr Asp Asp Asp Gly Arg Phe Val Glu Ser Lys Phe115 120 125Glu Glu Ile Phe Asn Lys His Ala Arg Thr His Lys Asp Ala Leu Thr130 135 140Ala Glu Glu Ile Gln Lys Met Leu Lys Thr Asn Arg Asp Pro Phe Asp145 150 155 160Ile Thr Gly Trp Phe Val Val Ser Glu Leu Phe Gln Thr Asn165 170
<210>120<211>192<212>PRT<213>Arabidopsis thaliana<400>120Met Ala Ser Ser Ile Ser A1a Ala Glu Val Lys Val Val Pro Glu Glu1 5 10 15Tyr Asn Phe Leu Gln Lys His Val Ala Phe Phe Asp Arg Asn Lys Asp20 25 30Gly Ile Val Tyr Pro Ser Glu Thr Phe Gln Gly Phe Arg Ala Ile Gly35 40 45Cys Gly Tyr Leu Leu Ser Thr Phe Ala Ala Val Phe Ile Asn Ile Ser50 55 60Leu Ser Ser Lys Thr Arg Pro Gly Lys Gly Phe Ser Phe Ser Phe Pro65 70 75 80Ile Glu Val Lys Asn Val Arg Leu Gly Ile His Ser Ser Asp Ser Gly85 90 95Val Tyr Asp Lys Asp Gly Arg Phe Val Ala Ser Lys Phe Glu Glu Ile100 105 110Phe Ala Lys His Ala His Thr His Arg Asp Ala Leu Thr Ser Lys Glu115 120 125Leu Lys Glu Leu Leu Lys Ala Asn Arg Glu Pro Asn Asp Cys Lys Gly130 135 140Gly Ile Leu Ala Phe Gly Glu Trp Lys Val Leu Tyr Asn Leu Cys Lys145 150 155 160Asp Lys Ser Gly Leu Leu His Lys Glu Ile Val Arg Ala Val Tyr Asp165 170 175Gly Ser Leu Phe Glu Gln Leu Glu Lys Gln Arg Ser Ser Lys Thr Pro180 185 190<210>121<211>195<212>PRT
<213>Arabidopsis thaliana<400>121Met Ala Ser Ser Ile Ser Thr Gly Val Lys Phe Val Pro Glu Glu Asp1 5 10 15Asn Phe Leu Gln Arg His Val Ala Phe Phe Asp Arg Asn Lys Asp Gly20 25 30Ile Val Tyr Pro Ser Glu Thr Phe Gln Gly Phe Arg Ala Ile Gly Cys35 40 45Gly Tyr Leu Leu Ser Ala Val Ala Ser Val Phe Ile Asn Ile Gly Leu50 55 60Ser Ser Lys Thr Arg Pro Gly Lys Gly Phe Ser Ile Trp Phe Pro Ile65 70 75 80Glu Val Lys Asn Ile His Leu Ala Lys His Gly Ser Asp Ser Gly Val85 90 95Tyr Asp Lys Asp Gly Arg Phe Val Ala Ser Lys Phe Glu Glu Ile Phe100 105 110Thr Lys His Ala His Thr His Arg Asp Ala Leu Thr Asn Glu Glu Leu115 120 125Lys Gln Leu Leu Lys Ala Asn Lys Glu Pro Asn Asp Arg Lys Gly Trp130 135 140Leu Ala Gly Tyr Thr Glu Trp Lys Val Leu His Tyr Leu Cys Lys Asp145 150 155 160Lys Asn Gly Leu Leu His Lys Asp Thr Val Arg Ala Ala Tyr Asp Gly165 70 175Ser Leu Phe Glu Lys Leu Glu Lys Gln Arg Ser Ser Lys Thr Ser Lys180 185 190Lys His Pro195<210>122<211>243<212>PRT
<213>Arabidopsis thaliana<400>122Met Thr Ser Met Glu Arg Met Glu Arg Asp Ala Met Glu Thr Val Ala1 5 10 15Pro Tyr Ala Arg Val Thr Tyr His Arg Arg Val Arg Gly Asp Leu Asp20 25 30Asp Thr Leu Pro Lys Pro Tyr Leu Pro Arg Ala Leu Gln Ala Pro Asp35 40 45Met Glu His Pro Gln Gly Thr Pro Asp His Arg His Asn Gly Leu Ser50 55 60Val Leu Gln Gln His Val Ala Phe Phe Asp Leu Asp Asn Asn Gly Ile65 70 75 80Ile Tyr Pro Phe Glu Thr Phe Ser Gly Phe Arg Leu Leu Gly Phe Asn85 90 95Leu Leu Ala Ser Leu Ile Leu Ala Ala Gly Ile Asn Ile Ala Leu Ser100 105 110Tyr Ala Thr Leu Pro Gly Trp Leu Pro Ser Pro Phe Phe Pro Ile Tyr115 120 125Ile His Asn Ile His Lys Ala Lys His Gly Ser Asp Ser Lys Thr Tyr130 135 140Asp Asn Glu Gly Arg Tyr Thr Pro Ala Asn Leu Glu Leu Met Phe Ser145 150 155 160Lys Tyr Ala Arg Thr Ile Pro Asp Lys Leu Ser Leu Gly Glu Leu Trp165 170 175Asp Met Thr Glu Gly Asn Arg Asp Ala Phe Asp Phe Phe Gly Trp Leu180 185 190Ala Ser Lys Val Glu Trp Gly Val Leu Tyr Ala Leu Ala Ser Asp Glu195 200 205Glu Gly Phe Leu Ser Lys Glu Ala Ile Arg Arg Cys Phe Asp Gly Ser210 215 220
Leu Phe Glu Tyr Cys Ala Lys Asn Tyr Ala Glu Ile Lys Glu Tyr Lys225 230 235 240Thr Tyr Tyr<210>123<211>175<212>PRT<213>Arabidopsis thaliana<400>123Met Cys Pro Ser Leu Thr Glu Thr Val Thr Ala Leu Phe Ile His Glu1 5 10 15Lys Pro Thr Lys Gly Phe Arg Ala Leu Gly Thr Gly Arg Phe Met Ser20 25 30Ala Phe Val Ala Val Phe Phe Asn Met Gly Leu Ser Gln Lys Thr Arg35 40 45Pro Val Gln Leu Phe Gly Tyr Ile Leu Pro Leu Phe Leu Lys Pro Phe50 55 60Val Cys Thr Val Val Thr Thr Asp Val Tyr Asp Lys Asp Gly Arg Phe65 70 75 80Val Glu Ser Lys Phe Glu Glu Ile Phe Asn Lys His Ala Arg Thr His85 90 95Lys Asp Ala Leu Thr Ala Lys Glu Ile Lys Gln Met Leu Lys Thr Asn100 105 110Arg Glu Pro Tyr Asp Phe Ile Gly Trp Leu Ser Asp Phe Ile Glu Trp115 120 125Lys Ile Leu His Thr Leu Ala Gln Asp Asn Gly Leu Leu Thr Glu Asp130 135 140Ala Val Arg Gly Val Tyr Asp Gly Ser Leu Phe Gln Gln Leu Glu Lys145 150 155 160LVs Arg Ser Ser Ser Ser Ser Arg Gly Lys Lys Gln Lys Leu Pro165 170 175
<210>124<211>184<212>PRT<213>Arabidopsis thaliana<400>124Met Thr Ala Leu Glu Lys His Val Ser Phe Phe Asp Arg Asn Lys Asp1 5 10 15Gly Thr Val Tyr Pro Trp Glu Thr Tyr Gln Gly Phe Arg Ala Leu Gly20 25 30Thr Gly Arg Leu Leu Ala Ala Phe Val Ala Ile Phe Ile Asn Met Gly35 40 45Leu Ser Lys Lys Thr Arg Pro Gly Lys Gly Phe Ser Pro Leu Phe Pro50 55 60Ile Asp Val Lys Asn Ser His Leu Cys Met His Gly Ser Asp Thr Asp65 70 75 80Val Tyr Asp Asp Asp Gly Arg Phe Val Glu Ser Lys Phe Glu Glu Ile85 90 95Phe Asn Lys His Ala Arg Thr His Lys Asp Ala Leu Thr Ala Glu Glu100 105 110Ile Gln Lys Met Leu Lys Thr Asn Arg Asp Pro Phe Asp Ile Thr Gly115 120 125Trp Leu Ser Asp Tyr Gly Glu Trp Lys Ile Leu His Thr Leu Ala Gln130 135 140Asp Lys Asn Gly Leu Leu Ser Glu Lys Ser Val Arg Ala Ile Tyr Asp145 150 155 160Gly Ser Leu Phe His Gln Leu Glu Lys Lys Arg Ser Ser Ser Ser Ser165 170 175Arg Gly Lys Lys Gln Lys Leu Pro180<210>125<211>246<212>PRT
<213>Hordeum vulgare<400>125Met Ala Gly Glu Asp Ala Thr Arg Ala Ala Thr Glu Glu Glu Leu Ser1 5 10 15Ser Val Ala Glu Ala Ala Pro Val Thr Ala Gln Arg Pro Val Arg Ser20 25 30Asp Leu Glu Lys Tyr Ile Pro Lys Pro Tyr Leu Ala Arg Ala Leu Val35 40 45Ala Pro Asp Val Tyr His Pro Gln Gly Ser Lys Glu Arg Gly His Glu50 55 60His Arg His Arg Ser Val Leu Gln Gln His Val Ala Phe Phe Asp Met65 70 75 80Asp Gly Asp Gly Val Ile Tyr Pro Trp Glu Thr Tyr Gln Gly Leu Arg85 90 95Ala Leu Gly Phe Asn Met Ile Val Ser Phe Val Ile Val Ile Ile Ile100 105 110His Ala Thr Leu Ser Tyr Thr Thr Leu Pro Ser Trp Val Pro Ser Leu115 120 125Leu Phe Pro Phe Tyr Ile Asp Asn Ile His Arg Ala Lys His Gly Ser130 135 140Asp Thr Ala Thr Tyr Asp Thr Glu Gly Arg Tyr Met Pro Val Asn Phe145 150 155 160Glu Asn Ile Phe Ser Lys Asn Ala Arg Ser Ser Pro Asp Lys Leu Thr165 170 175Phe Arg Glu Ile Trp Thr Met Thr Asp Asp Gln Arg Gln Ala Asn Asp180 185 190Pro Phe Gly Trp Val Ala Ser Lys Ala Glu Trp Ile Leu Leu Tyr Met195 200 205Leu Ala Lys Asp Glu Glu Gly Asn Leu Pro Arg Glu Ala Ile Arg Arg210 215 220
Cys Phe Asp Gly Ser Leu Phe Glu Phe Ile Ala Asp Glu Arg Arg Gln225 230 235 240Ala His Gly Lys Gln Tyr245<210>126<211>246<212>PRT<213>Hordeum vulgare<400>126Met Ala Gly Glu Asp Ala Thr Arg Ala Ala Thr Glu Glu Glu Leu Ser5 10 15Ser Val Ala Glu Ala Ala Pro Val Thr Ala Gln Arg Pro Val Arg Ser20 25 30Asp Leu Glu Lys Tyr Ile Pro Lys Pro Tyr Leu Ala Arg Ala Leu Val35 40 45Ala Pro Asp Val Tyr His Pro Gln Gly Ser Lys Glu Arg Gly His Glu50 55 60His Arg His Arg Ser Val Leu Gln Gln His Val Ala Phe Phe Asp Met65 70 75 80Asp Gly Asp Gly Val Ile Tyr Pro Trp Glu Thr Tyr Gln Gly Leu Arg85 90 95Ala Leu Gly Phe Asn Met Ile Val Ser Phe Val Ile Val Ile Ile Ile100 105 110His Ala Thr Leu Ser Tyr Thr Thr Leu Pro Ser Trp Val Pro Ser Leu115 120 125Leu Phe Pro Phe Tyr Ile Asp Asn Ile His Arg Ala Lys His Gly Ser130 135 140Asp Thr Ala Thr Tyr Asp Thr Glu Gly Arg Tyr Met Pro Val Asn Phe145 150 155 160Glu Asn Ile Phe Ser Lys Asn Ala Arg Ser Ser Pro Asp Lys Leu Thr165 170 175
Phe Arg Glu Ile Trp Thr Met Thr Asp Asp Gln Arg Gln Ala Asn Asp180 185 190Pro Phe Gly Trp Val Ala Ser Lys Ala Glu Trp Ile Leu Leu Tyr Met195 200 205Leu Ala Lys Asp Glu Glu Gly Asn Leu Pro Arg Glu Ala Ile Arg Arg210 215 220Cys Phe Asp Gly Ser Leu Phe Glu Phe Ile Ala Asp Glu Arg Arg Gln225 230 235 240Ala His Gly Lys Gln Tyr245<210>127<211>301<212>PRT<213>Hordeum vulgare<400>127Met Ala Thr Lys Ala Arg Lys Val Glu Val Arg Asp Ala Ser Arg Ala1 5 10 15Glu Gly Lys Gly Asp Ala Ala Asp Val His Val Leu Arg Glu Ala Met20 25 30Arg Ala Asp Gly Lys Gly Asp His Asp Thr Ala Gly Gly Ala Asn Arg35 40 45Ala Asp Gly His Gly Asp Ala Gly Gly Arg Val Gly Asp Ser Arg Gly50 55 60Val Asp Gly Lys Asp Ser Leu Lys Met Val Ala Lau Gln Ala Pro Val65 70 75 80Thr Val Glu Arg Pro Val Arg Gly Asp Leu Glu Glu His Val Pro Lys85 90 95Pro Tyr Leu Ala Arg Ala Leu Ala Ala Pro Asp Met Tyr His Pro Glu100 105 110Gly Thr Thr Thr Asp Asp His Gln His His Asn Met Ser Val Leu Gln115 120 125
Gln His Val Ala Phe Phe Asp Arg Asp Asn Asn Gly Ile Ile Tyr Pro130 135 140Trp Glu Thr Tyr Asp Gly Cys Arg Ala Val Gly Phe Asn Val Phe Met145 150 155 160Ser Ala Phe Ile Ala Phe Leu Val Asn Leu Val Met Ser Tyr Pro Thr165 170 175Leu Pro Gly Trp Leu Pro Asn Pro Leu Phe Pro Ile Tyr Val His Asn180 185 190Ile His Lys Ser Lys His Gly Ser Asp Ser Gly Thr Tyr Asp Lys Glu195 200 205Gly Arg Phe Met Pro Val Asn Phe Glu Asn Ile Phe Ser Lys Tyr Ala210 15 220Arg Thr Tyr Pro Asp Arg Leu Ser Tyr Arg Glu Met Trp Arg Met Thr225 230 235 240Glu Gly Cys Arg Glu Val Phe Asp Phe Phe Gly Trp Val Ala Met Lys245 250 255Leu Glu Trp Ser Ile Leu Tyr Ala Leu Ala Arg Asp Asp Glu Gly Tyr260 265 270Leu Ser Arg Glu Ala Ile Arg Arg Met Tyr Asp Gly Ser Leu Phe Glu275 280 285Tyr Met Glu Arg Gln Arg Met Glu His Val Lys Met Ser290 295 300<210>128<211>301<212>PRT<213>Hordeum vulgare<400>128Met Ala Thr Lys Ala Arg Lys Val Glu Val Arg Asp Ala Ser Arg Ala1 5 10 15Glu Gly Lys Gly Asp Ala Ala Asp Val His Val Leu Arg Glu Ala Met20 25 30
Arg Ala Asp Gly Lys Gly Asp His Asp Thr Ala Gly Gly Ala Asn Arg35 40 45Ala Asp Gly His Gly Asp Ala Gly Gly Arg Val Gly Asp Ser Arg Gly50 55 60Val Asp Gly Lys Asp Ser Leu Lys Met Val Ala Leu Gln Ala Pro Val65 70 75 80Thr Val Glu Arg Pro Val Arg Gly Asp Leu Glu Glu His Val Pro Lys85 90 95Pro Tyr Leu Ala Arg Ala Leu Ala Ala Pro Asp Met Tyr His Pro Glu100 105 110Gly Thr Thr Thr Asp Asp His Gln His His Asn Met Ser Val Leu Gln115 120 125Gln His Val Ala Phe Phe Asp Arg Asp Asn Asn Gly Ile Ile Tyr Pro130 135 140Trp Glu Thr Tyr Asp Gly Cys Arg Ala Val Gly Phe Asn Val Phe Met145 150 155 160Ser Ala Phe Ile Ala Phe Leu Val Asn Leu Val Met Ser Tyr Pro Thr165 170 175Leu Pro Gly Trp Leu Pro Asn Pro Leu Phe Pro Ile Tyr Val His Asn180 185 190Ile His Lys Ser Lys His Gly Ser Asp Ser Gly Thr Tyr Asp Lys Glu195 200 205Gly Arg Phe Met Pro Val Asn Phe Glu Asn Ile Phe Ser Lys Tyr Ala210 215 220Arg Thr Tyr Pro Asp Arg Leu Ser Tyr Arg Glu Met Trp Arg Met Thr225 230 235 240Glu Gly Cys Arg Glu Val Phe Asp Phe Phe Gly Trp Val Ala Met Lys245 250 255Leu Glu Trp Ser Ile Leu Tyr Ala Leu Ala Arg Asp Asp Glu Gly Tyr260 265 270
Leu Ser Arg Glu Ala Ile Arg Arg Met Tyr Asp Gly Ser Leu Phe Glu275 280 285Tyr Met Glu Arg Gln Arg Met Glu His Val Lys Met Ser290 295 300<210>129<211>245<212>PRT<213>Sesamum indicum<400>129Met Ala Thr His Val Leu Ala Ala Ala Ala Glu Arg Asn Ala Ala Leu1 5 10 15Ala Pro Asp Ala Pro Leu Ala Pro Val Thr Met Glu Arg Pro Val Arg20 25 30Thr Asp Leu Glu Thr Ser Ile Pro Lys Pro Tyr Met Ala Arg Gly Leu35 40 45Val Ala Pro Asp Met Asp His Pro Asn Gly Thr Pro Gly His Val His50 55 60Asp Asn Leu Ser Val Leu Gln Gln His Cys Ala Phe Phe Asp Gln Asp65 70 75 80Asp Asn Gly Ile Ile Tyr Pro Trp Glu Thr Tyr Ser Gly Leu Arg Gln85 90 95Ile Gly Phe Asn Val Ile Ala Ser Leu Ile Met Ala Ile Val Ile Asn100 105 110Val Ala Leu Ser Tyr Pro Thr Leu Pro Gly Trp Ile Pro Ser Pro Phe115 120 125Phe Pro Ile Tyr Leu Tyr Asn Ile His Lys Ala Lys His Gly Ser Asp130 135 140Ser Gly Thr Tyr Asp Thr Glu Gly Arg Tyr Leu Pro Met Asn Phe Glu145 150 155 160Asn Leu Phe Ser Lys His Ala Arg Thr Met Pro Asp Arg Leu Thr Leu165 170 175
Gly Glu Leu Trp Ser Met Thr Glu Ala Asn Arg Glu Ala Phe Asp Ile180 185 190Phe Gly Trp Ile Ala Ser Lys Met Glu Trp Thr Leu Leu Tyr Ile Leu195 200 205Ala Arg Asp Gln Asp Gly Phe Leu Ser Lys Glu Ala Ile Arg Arg Cys210 215 220Tyr Asp Gly Ser Leu Phe Glu Tyr Cys Ala Lys Met Gln Arg Gly Ala225 230 235 240Glu Asp Lys Met Lys245<210>130<211>395<212>PRT<213>Oryza sativa<400>130Met Asp Leu Tyr Leu Met Phe His Ser Val Leu Met His Val Ala Ala1 5 10 15Ala Leu Val Val Leu Val Tyr Ile Pro Leu Ser Met Pro Val Lys Leu20 25 30Phe Leu Trp Ala Phe Val Lys Pro Leu Arg Lys Glu Ser Leu Arg Gly35 40 45Lys Val Val Leu Ile Thr Gly Ala Ser Ser Gly Ile Gly Glu Glu Leu50 55 60Ala Tyr Gln Tyr Ala Ala Gln Gly Ala Cys Leu Ala Leu Val Ala Arg65 70 75 80Arg Lys Lys Ala Leu Glu Gly Val Ala Ala Ala Ala Leu Glu Arg Gly85 90 95Ser Pro Asp Val Leu Val Leu Pro Ala Asp Val Ser Asp Ala Asp Gln100 105 110Ser Arg Arg Ala Val Glu Glu Thr Val Ala His Phe Gly Lys Leu Asn115 120 125
His Leu Val Ala Asn Ala Gly Ile Trp Ser Ser Cys Ser Phe Asp Glu130 135 140Val Thr Asn Ile Thr Ala Phe Thr Lys Met Met Asp Val Asn Phe Trp145 150 155 160Gly Ser Val Tyr Pro Thr Tyr Tyr Ala Leu Pro His Leu Lys Ala Ser165 170 175Lys Gly Lys Leu Val Val Ser Cys Ser Ala Ala Gly Thr Val Gly Thr180 185 190Ser Arg Met Ser Phe Tyr Asn Ala Thr Lys Ala Ala Gln Leu Arg Phe195 200 205Tyr Glu Thr Leu Arg Ala Glu Leu Gly Ser Glu Val Gly Ile Thr Val210 215 220Leu Thr Pro Gly Tyr Val Glu Ser Glu Ile Thr Lys Gly Lys Gly Ile225 230 235 240Gln Ser Gly Gly Asp Val Ala Val Asn Glu Glu Ala Arg Asp Glu Gln245 250 255Ile Gly Val Phe Pro Val Gly Arg Val Ala Glu Leu Gly Glu Val Ala260 265 270Met Asp Gly Ile Arg Ala Gly Asp Trp Tyr Val Thr Trp Pro Ser Leu275 280 285Phe Arg Pro Leu Gln Leu Val Ala Cys Leu Ala Pro Gly Val Leu Asp290 295 300Trp Ala Cys Arg Ala Leu Tyr Gly Thr Arg Lys Gly Ala Arg Pro Pro305 310 315 320Leu Gly Lys Arg Ile Met Glu Ala Thr Gly Met Lys Arg Leu Phe Pro325 330 335Glu Ala Leu Arg Arg Asn Pro Ala Ile Lys Thr Glu Asp Glu Glu Tyr340 345 350Cys Asp Gly Glu Glu Gly Tyr Gly Ala Ala Asp Asp Ala Ala Ala Ala
355 360 365Tyr Leu Leu Gln Cys Arg Lys Gly Leu Arg Ala Ala His Thr Tyr Ile370 375 380Arg Cys Ile Phe Ser Leu Ser Asp Ser Ile Leu385 390 395<210>131<211>357<212>PRT<213>Oryza sativa<400>131Met Lys Thr Gln Leu Phe Ser Asp Asp Ala Leu Ser Val Met Lys Glu1 5 10 15Ala Cys Ile Leu Val Val Ala Ser Leu Glu Ile Asn Gln Met Asp Gly20 25 30Ala Thr Phe Cys Glu Ala Asn Leu Phe Tyr Phe Gln Phe Glu Asp Gly35 40 45His Arg Asp Lys Arg Asn Val Thr Leu Glu Leu Ala Tyr Gln Tyr Ala50 55 60Ser Lys Gly Ala Ser Leu Ala Leu Val Ala Arg Arg Lys Gln Ala Leu65 70 75 80Lys Ser Val Ala Ala Ala Ala Arg Glu Arg Gly Ala Pro Asp Val Leu85 90 95Val Leu Asp Ala Asp Val Ser Asp Ala Gly Gln Ser Arg Arg Ala Val100 105 110Glu Glu Thr Ile Ala His Tyr Gly Lys Leu Asn His Leu Val Ala Asn115 120 125Ala Gly Ile Trp Ser Thr Cys Pro Phe Asp Glu Ile Thr Asn Ile Thr130 135 140Ala Phe Thr Thr Ile Met Asp Val Asn Phe Trp Gly Ala Val Tyr Pro145 150 155 160Thr Tyr Tyr Ala Leu Pro His Leu Lys Ala Ser Arg Gly Lys Leu Val
165 170 175Val Cys Ser Ser Ala Ala Gly Thr Val Ala Thr Ser Arg Met Ser Phe180 185 190Tyr Asn Ala Ser Lys Ala Ala Val Leu Arg Phe Tyr Glu Thr Leu Arg195 200 205Ala Glu Leu Gly Ser Glu Val Gly Val Thr Ile Leu Thr His Gly Tyr210 215 220Val Glu Ser Glu Met Thr Met Gly Lys Ala Val Gln Lys Asp Gly Val225 230 235 240Leu Val Val Asp Gln Glu Ala Arg Asp Val Gln Ile Gly Val Phe Pro245 250 255Val Gly Gly Val Gly Ala Met Cys Arg Val Ala Met Asp Gly Ile Arg260 265 270Arg Gly Asp Arg Tyr Val Thr Trp Pro Ser Val Tyr Arg Pro Leu Gln275 280 285Leu Val Ala Cys Leu Ala Pro Glu Ile Val Ser Trp Leu Ser Tyr Ala290 295 300Met Tyr Asn Thr Lys Ala Gly Gly Gly Ala Pro Leu Ser Lys Arg Ala305 310 315 320Leu Asp Ala Thr Gly Ala Arg Arg Phe Phe Pro Glu Gly Leu Arg Arg325 30 335Asn Pro Val Val Ile Lys Thr Asp Glu Glu Cys Asp Gly Asp Glu Gly340 45 350Val Ala Ala Cys Asn355<210>132<211>355<212>PRT<213>Oryza sativa<400>132Met Glu Gln Val Val Asn Ala Val Leu Asp Leu Val Val Pro Pro Ala
1 5 10 15Ser Met Val Met Leu Ala Phe Ala Trp Pro Thr Leu Ser Phe Leu Arg20 25 30Gly Val Glu Trp Val Val Lys Thr Leu Thr Val Glu Asn Met His Asn35 40 45Lys Val Val Leu Ile Thr Gly Ala Ser Ser Ala Ile Gly Glu Gln Ile50 55 60Ala Tyr Glu Tyr Ala Arg Arg Asn Ala Asn Leu Val Leu Val Ala Arg65 70 75 80Arg Glu His Arg Leu Phe Ala Val Arg Glu Asn Ala Arg Ala Leu Gly85 90 95Ala Gly Gln Val Leu Val Ile Ala Ala Asp Val Val Lys Glu Asp Asp100 105 110Cys Arg Arg Leu Val Gly Asp Thr Ile Ser Phe Phe Gly Gln Leu Asn115 120 125His Leu Val Asn Thr Val Ser Leu Gly His Asp Phe Cys Phe Glu Glu130 135 140Ala Gly Asp Thr Val Ala Phe Pro His Leu Met Asp Val Asn Phe Trp145 150 155 160Gly Asn Val Tyr Pro Thr Tyr Ala Ala Leu Pro Tyr Leu Arg Arg Ser165 170 175His Gly Arg Val Val Val Asn Ala Ala Val Glu Ile Trp Leu Pro Met180 185 190Pro Arg Met Thr Leu Tyr Ser Ala Ala Lys Ala Ala Val Ile Asp Phe195 200 205Tyr Glu Ser Leu Arg Tyr Glu Val Gly Asp Glu Val Gly Ile Ser Val210 215 220Ala Thr His Gly Trp Ile Gly Gly Glu Ala Ser Gly Gly Lys Phe Met225 230 235 240
Leu Glu Glu Gly Ala Glu Met Gln Trp Lys Gly Glu Glu Arg Glu Val245 250 255Pro Leu Ala Gly Gly Gln Val Glu Ala Tyr Ala Arg Met Val Val Ala260 265 270Gly Ala Cys Arg Gly Asp Ala His Val Lys His Pro Asn Trp Tyr Asp275 280 285Val Phe Leu Val Phe Arg Ala Phe Ala Pro Asp Val Leu Ala Trp Thr290 295 300Phe Arg Leu Leu Leu Ser Thr Pro Ser Pro Ser Pro Pro Ala Ser Ala305 310 315 320Arg Arg His Gln Leu Ala Ala Leu Pro Ala Pro Pro Leu His Pro Leu325 330 335Leu Glu Tyr Pro Ser Ala Arg Ser Pro Gly Arg Ala Ala Gln Gln His340 345 350Lys Leu Glu355<210>133<211>395<212>PRT<213>Oryza sativa<400>133Met Asp Leu Tyr Leu Met Phe His Ser Val Leu Met His Val Ala Ala1 5 10 15Ala Leu Val Val Leu Val Tyr Ile Pro Leu Ser Met Pro Val Lys Leu20 25 30Phe Leu Trp Ala Phe Val Lys Pro Leu Arg Lys Glu Ser Leu Arg Gly35 40 45Lys Val Val Leu Ile Thr Gly Ala Ser Ser Gly Ile Gly Glu Glu Leu50 55 60Ala Tyr Gln Tyr Ala Ala Gln Gly Ala Cys Leu Ala Leu Val Ala Arg65 70 75 80
Arg Lys Lys Ala Leu Glu Gly Val Ala Ala Ala Ala Leu Glu Arg Gly85 90 95Ser Pro Asp Val Leu Val Leu Pro Ala Asp Val Ser Asp Ala Asp Gln100 105 110Ser Arg Arg Ala Val Glu Glu Thr Val Ala His Phe Gly Lys Leu Asn115 120 125His Leu Val Ala Asn Ala Gly Ile Trp Ser Ser Cys Ser Phe Asp Glu130 135 140Val Thr Asn Ile Thr Ala Phe Thr Lys Met Met Asp Val Asn Phe Trp145 150 155 160Gly Ser Val Tyr Pro Thr Tyr Tyr Ala Leu Pro His Leu Lys Ala Ser165 170 175Lys Gly Lys Leu Val Val Ser Cys Ser Ala Ala Gly Thr Val Gly Thr180 185 190Ser Arg Met Ser Phe Tyr Asn Ala Thr Lys Ala Ala Gln Leu Arg Phe195 200 205Tyr Glu Thr Leu Arg Ala Glu Leu Gly Ser Glu Val Gly Ile Thr Val210 215 220Leu Thr Pro Gly Tyr Val Glu Ser Glu Ile Thr Lys Gly Lys Gly Ile225 230 235 240Gln Ser Gly Gly Asp Val Ala Val Asn Glu Glu Ala Arg Asp Glu Gln245 250 255Ile Gly Val Phe Pro Val Gly Arg Val Ala Glu Leu Gly Glu Val Ala260 265 270Met Asp Gly Ile Arg Ala Gly Asp Trp Tyr Val Thr Trp Pro Ser Leu275 280 285Phe Arg Pro Leu Gln Leu Val Ala Cys Leu Ala Pro Gly Val Leu Asp290 295 300Trp Ala Cys Arg Ala Leu Tyr Gly Thr Arg Lys Gly Ala Arg Pro Pro305 310 315 320
Leu Gly Lys Arg Ile Met Glu Ala Thr Gly Met Lys Arg Leu Phe Pro325 330 335Glu Ala Leu Arg Arg Asn Pro Ala Ile Lys Thr Glu Asp Glu Glu Tyr340 345 350Cys Asp Gly Glu Glu Gly Tyr Gly Ala Ala Asp Asp Ala Ala Ala Ala355 360 365Tyr Leu Leu Gln Cys Arg Lys Gly Leu Arg Ala Ala His Thr Tyr Ile370 375 380Arg Cys Ile Phe Ser Leu Ser Asp Ser Ile Leu385 390 395<210>134<211>357<212>PRT<213>Oryza sativa<400>134Met Lys Thr Gln Leu Phe Ser Asp Asp Ala Leu Ser Val Met Lys Glu1 5 10 15Ala Cys Ile Leu Val Val Ala Ser Leu Glu Ile Asn Gln Met Asp Gly20 25 30Ala Thr Phe Cys Glu Ala Asn Leu Phe Tyr Phe Gln Phe Glu Asp Gly35 40 45His Arg Asp Lys Arg Asn Val Thr Leu Glu Leu Ala Tyr Gln Tyr Ala50 55 60Ser Lys Gly Ala Ser Leu Ala Leu Val Ala Arg Arg Lys Gln Ala Leu65 70 75 80Lys Ser Val Ala Ala Ala Ala Arg Glu Arg Gly Ala Pro Asp Val Leu85 90 95Val Leu Asp Ala Asp Val Ser Asp Ala Gly Gln Ser Arg Arg Ala Val100 105 110Glu Glu Thr Ile Ala His Tyr Gly Lys Leu Asn His Leu Val Ala Asn115 120 125
Ala Gly Ile Trp Ser Thr Cys Pro Phe Asp Glu Ile Thr Asn Ile Thr130 135 140Ala Phe Thr Thr Ile Met Asp Val Asn Phe Trp Gly Ala Val Tyr Pro145 150 155 160Thr Tyr Tyr Ala Leu Pro His Leu Lys Ala Ser Arg Gly Lys Leu Val165 170 175Val Cys Ser Ser Ala Ala Gly Thr Val Ala Thr Ser Arg Met Ser Phe180 185 190Tyr Asn Ala Ser Lys Ala Ala Val Leu Arg Phe Tyr Glu Thr Leu Arg195 200 205Ala Glu Leu Gly Ser Glu Val Gly Val Thr Ile Leu Thr His Gly Tyr210 215 220Val Glu Ser Glu Met Thr Met Gly Lys Ala Val Gln Lys Asp Gly Val225 230 235 240Leu Val Val Asp Gln Glu Ala Arg Asp Val Gln Ile Gly Val Phe Pro245 250 255Val Gly Gly Val Gly Ala Met Cys Arg Val Ala Met Asp Gly Ile Arg260 265 270Arg Gly Asp Arg Tyr Val Thr Trp Pro Ser Val Tyr Arg Pro Leu Gln275 280 285Leu Val Ala Cys Leu Ala Pro Glu Ile Val Ser Trp Leu Ser Tyr Ala290 295 300Met Tyr Asn Thr Lys Ala Gly Gly Gly Ala Pro Leu Ser Lys Arg Ala305 310 315 320Leu Asp Ala Thr Gly Ala Arg Arg Phe Phe Pro Glu Gly Leu Arg Arg325 330 335Asn Pro Val Val Ile Lys Thr Asp Glu Glu Cys Asp Gly Asp Glu Gly340 345 350Val Ala Ala Cys Asn355
<210>135<211>362<212>PRT<213>Sesamum indicum<400>135Met Asp Leu Ile Asn Ser Leu Leu Asn Phe Val Val Pro Pro Ala Ser1 5 10 15Leu Leu Met Leu Ala Phe Thr Trp Pro Thr Leu Phe Phe Ile Thr Thr20 25 30Cys Glu Trp Leu Tyr Asn Thr Tyr Leu Asn Ser Glu Asn Met Glu Asn35 40 45Lys Val Val Leu Ile Thr Gly Ala Ser Ser Gly Ile Gly Glu Gln Ile50 55 60Ala Tyr Gln Tyr Ala Lys Arg Gly Ala Asn Leu Val Leu Val Ala Arg65 70 75 80Arg Glu His Arg Leu Arg Gly Ile Ser Glu Asn Ala Arg Arg Leu Gly85 90 95Ala Pro Asn Val Leu Ile Met Ala Ala Asp Val Val Lys Glu Glu Glu100 105 110Cys Arg Arg Phe Ile Asn Glu Thr Ile Asn Tyr Tyr Gly Arg Val Asp115 120 125His Leu Val Asn Thr Val Ser Leu Gly His Thr Phe Tyr Phe Glu Glu130 135 140Ala Ser Asp Ser Ser Val Phe Pro Ile Leu Met Asp Ile Asn Phe Trp145 150 155 160Gly Asn Val Tyr Pro Thr Tyr Val Ala Leu Pro Tyr Leu Arg Glu Ser165 170 175Asn Gly Arg Ile Ile Val Asn Ala Ser Val Glu Asn Trp Leu Pro Leu180 185 190Pro Arg Met Ser Leu Tyr Ser Ala Ala Lys Ser Ala Leu Ile Asn Phe195 200 205
Tyr Glu Thr Leu Arg Phe Glu Val Lys Asn Glu Val Gly Ile Thr Val210 215 220Ala Thr His Gly Trp Ile Gly Thr Glu Met Thr Arg Gly Lys Phe Met225 230 235 240Val Glu Glu Gly Ala Glu Met Gln Trp Lys Glu Glu Arg Glu Val His245 250 255Val Thr Gly Gly Pro Val Glu Glu Phe Ala Lys Gln Ile Val Ser Gly260 265 270Ala Cys Arg Gly Asp Pro Tyr Val Lys Tyr Pro Ser Trp Tyr Asp Ile275 280 285Phe Phe Leu Tyr Arg Val Phe Ala Pro Lys Val Leu Asp Trp Thr Phe290 295 300Arg Phe Leu Leu Thr Asn Gly Gly Ala Arg Arg Thr Ser Phe Ile Gly305 310 315 320Thr Gly Arg Pro Leu Leu Glu Thr Ser Ser Pro Arg Arg Ser Ala Val325 330 335Met Glu Gly Ser Ser Pro Arg Arg Leu Pro Pro Gly Pro Leu Thr Phe340 345 350Ser Pro Ala Phe Gln Gln Gln Lys Ser Glu355 360<210>136<211>348<212>PRT<213>Sesamum indicum<400>136Met Asp Leu Ile His Thr Phe Leu Asn Leu Ile Ala Pro Pro Phe Thr1 5 10 15Phe Phe Phe Leu Leu Phe Phe Leu Pro Pro Phe Gln Ile Phe Lys Phe20 25 30Phe Leu Ser Ile Leu Gly Thr Leu Phe Ser Glu Asp Val Ala Gly Lys35 40 45
Val Val Val Ile Thr Gly Ala Ser Ser Gly Ile Gly Glu Ser Leu Ala50 55 60Tyr Glu Tyr Ala Lys Arg Gly Ala Cys Leu Val Leu Ala Ala Arg Arg65 70 75 80Glu Arg Ser Leu Gln Glu Val Ala Glu Arg Ala Arg Asp Leu Gly Ser85 90 95Pro Asp Val Val Val Val Arg Ala Asp Val Ser Lys Ala Glu Asp Cys100 105 110Arg Lys Val Val Asp Gln Thr Met Asn Arg Phe Gly Arg Leu Asp His115 120 125Leu Val Asn Asn Ala Gly Ile Met Ser Val Ser Met Leu Glu Glu Val130 135 140Glu Asp Ile Thr Gly Tyr Arg Glu Thr Met Asp Ile Asn Phe Trp Gly145 150 155 160Tyr Val Tyr Met Thr Arg Phe Ala Ala Pro Tyr Leu Arg Asn Ser Arg165 170 175Gly Arg Ile Val Val Leu Ser Ser Ser Ser Ser Trp Met Pro Thr Pro180 185 190Arg Met Ser Phe Tyr Asn Ala Ser Lys Ala Ala Ile Ser Gln Phe Phe195 200 205Glu Thr Leu Arg Val Glu Phe Gly Pro Asp Ile Gly Ile Thr Leu Val210 215 220Thr Pro Gly Phe Ile Glu Ser Glu Leu Thr Gln Gly Lys Phe Tyr Asn225 230 235 240Ala Gly Glu Arg Val Ile Asp Gln Asp Met Arg Asp Val Gln Val Ser245 250 255Thr Thr Pro Ile Leu Arg Val Glu Ser Ala Ala Arg Ser Ile Val Arg260 265 270Ser Ala Ile Arg Gly Glu Arg Tyr Val Thr Glu Pro Ala Trp Phe Arg
275 280 285Val Thr Tyr Trp Trp Lys Leu Phe Cys Pro Glu Val Met Glu Trp Val290 295 300Phe Arg Leu Met Tyr Leu Ala Ser Pro Gly Glu Pro Glu Lys Glu Thr305 310 315 320Phe Gly Lys Lys Val Leu Asp Tyr Thr Gly Val Lys Ser Leu Leu Tyr325 330 335Pro Glu Thr Val Gln Val Pro Glu Pro Lys Asn Asp340 345<210>137<211>348<212>PRT<213>Sesamum indicum<400>137Met Asp Leu Ile His Thr Phe Leu Asn Leu Ile Ala Pro Pro Phe Thr1 5 10 15Phe Phe Phe Leu Leu Phe Phe Leu Pro Pro Phe Gln Ile Phe Lys Phe20 25 30Phe Leu Ser Ile Leu Gly Thr Leu Phe Ser Glu Asp Val Ala Gly Lys35 40 45Val Val Val Ile Thr Gly Ala Ser Ser Gly Ile Gly Glu Ser Leu Ala50 55 60Tyr Glu Tyr Ala Lys Arg Gly Ala Cys Leu Val Leu Ala Ala Arg Arg65 70 75 80Glu Arg Ser Leu Gln Glu Val Ala Glu Arg Ala Arg Asp Leu Gly Ser85 90 95Pro Asp Val Val Val Val Arg Ala Asp Val Ser Lys Ala Glu Asp Cys100 105 110Arg Lys Val Val Asp Gln Thr Met Asn Arg Phe Gly Arg Leu Asp His115 120 125Leu Val Asn Asn Ala Gly Ile Met Ser Val Ser Met Leu Glu Glu Val
130 135 140Glu Asp Ile Thr Gly Tyr Arg Glu Thr Met Asp Ile Asn Phe Trp Gly145 150 155 160Tyr Val Tyr Met Thr Arg Phe Ala Ala Pro Tyr Leu Arg Asn Ser Arg165 170 175Gly Arg Ile Val Val Leu Ser Ser Ser Ser Ser Trp Met Pro Thr Pro180 185 190Arg Met Ser Phe Tyr Asn Ala Ser Lys Ala Ala Ile Ser Gln Phe Phe195 200 205Glu Thr Leu Arg Val Glu Phe Gly Pro Asp Ile Gly Ile Thr Leu Val210 215 220Thr Pro Gly Phe Ile Glu Ser Glu Leu Thr Gln Gly Lys Phe Tyr Asn225 230 235 240Ala Gly Glu Arg Val Ile Asp Gln Asp Met Arg Asp Val Gln Val Ser245 250 255Thr Thr Pro Ile Leu Arg Val Glu Ser Ala Ala Arg Ser Ile Val Arg260 265 270Ser Ala Ile Arg Gly Glu Arg Tyr Val Thr Glu Pro Ala Trp Phe Arg275 280 285Val Thr Tyr Trp Trp Lys Leu Phe Cys Pro Glu Val Met Glu Trp Val290 295 300Phe Arg Leu Met Tyr Leu Ala Ser Pro Gly Glu Pro Glu Lys Glu Thr305 310 315 320Phe Gly Lys Lys Val Leu Asp Tyr Thr Gly Val Lys Ser Leu Leu Tyr325 330 335Pro Glu Thr Val Gln Val Pro Glu Pro Lys Asn Asp340 345<210>138<211>118<212>PRT<213>Arabidopsis thaliana
<400>138Met Ala Asp Thr Ala Arg Gly Thr His His Asp Ile Ile Gly Arg Asp1 5 10 15Gln Tyr Pro Met Met Gly Arg Asp Arg Asp Gln Tyr Gln Met Ser Gly20 25 30Arg Gly Ser Asp Tyr Ser Lys Ser Arg Gln Ile Ala Lys Ala Ala Thr35 40 45Ala Val Thr Ala Gly Gly Ser Leu Leu Val Leu Ser Ser Leu Thr Leu50 55 60Val Gly Thr Val Ile Ala Leu Thr Val Ala Thr Pro Leu Leu Val Ile65 70 75 80Phe Ser Pro Ile Leu Val Pro Ala Leu Ile Thr Val Ala Leu Leu Ile85 90 95Thr Gly Phe Leu Ser Ser Gly Gly Phe Gly Ile Ala Ala Ile Thr Val100 105 110Phe Ser Trp Ile Tyr Lys115<210>139<211>187<212>PRT<213>Brassica napus<400>139Met Ala Asp Thr Ala Arg Thr His His Asp Val Thr Ser Arg Asp Gln1 5 10 15Tyr Pro Arg Asp Arg Asp Gln Tyr Ser Met Ile Gly Arg Asp Arg Asp20 25 30Gln Tyr Ser Met Met Gly Arg Asp Arg Asp Gln Tyr Asn Met Tyr Gly35 40 45Arg Asp Tyr Ser Lys Ser Arg Gln Ile Ala Lys Ala Val Thr Ala Val50 55 60Thr Ala Gly Gly Ser Leu Leu Val Leu Ser Ser Leu Thr Leu Val Gly
65 70 75 80Thr Val Ile Ala Leu Thr Val Ala Thr Pro Leu Leu Val Ile Phe Ser85 90 95Pro Ile Leu Val Pro Ala Leu Ile Thr Val Ala Leu Leu Ile Thr Gly100 105 110Phe Leu Ser Ser Gly Gly Phe Ala Ile Ala Ala Ile Thr Val Phe Ser115 120 125Trp Ile Tyr Lys Tyr Ala Thr Gly Glu His Pro Gln Gly Ser Asp Lys130 135 140Leu Asp Ser Ala Arg Met Lys Leu Gly Thr Lys Ala Gln Asp Ile Lys145 150 155 160Asp Arg Ala Gln Tyr Tyr Gly Gln Gln His Thr Gly Gly Glu His Asp165 170 175Arg Asp Arg Thr Arg Gly Gly Gln His Thr Thr180 185<210>140<211>748<212>DNA<213>Arabidopsis thaliana<400>140taccatgggg tcaaagacgg agatgatgga gagagacgca atggctacgg tggctcccta 60tgcgccggtc acttaccatc gccgtgctcg tgttgacttg gatgatagac ttcctaaacc120ttatatgcca agagcattgc aagcaccaga cagagaacac ccgtacggaa ctccaggcca180taagaattac ggacttagtg ttcttcaaca gcatgtctcc ttcttcgata tcgatgataa240tggcatcatt tacccttggg agacctactc tggactgcga atgcttggtt tcaatatcat300tgggtcgctt ataatagccg ctgttatcaa cctgaccctt agctatgcca ctcttccggg360gtggttacct tcacctttct tccctatata catacacaac atacacaagt caaagcatgg420aagtgattca aaaacatatg acaatgaagg aaggtttatg ccggtgaatc ttgagttgat480atttagcaaa tatgcgaaaa ccttgccaga caagttgagt cttggagaac tatgggagat540gacagaagga aaccgtgacg cttgggacat ttttggatgg atcgcaggca aaatagagtg600gggactgttg tacttgctag caagggatga agaagggttt ttgtcaaaag aagctattag660
gcggtgtttc gatggaagct tgttcgagta ctgtgccaaa atctacgctg gtatcagtga720agacaagaca gcatactacg ccatggat 748<210>141<211>738<212>DNA<213>Arabidopsis thaliana<400>141atggggtcaa agacggagat gatggagaga gacgcaatgg ctacggtggc tccctatgcg 60ccggtcactt accaccgccg tgctcgtgtt gacttggatg atagacttcc taaaccttat120atgccaagag cattgcaagc accagacaga gaacacccgt acggaactcc aggccataag180aattacggac ttagtgttct tcaacagcat gtctccttct tcgatatcga tgataatggc240atcatttacc cttgggagac ctactctgga ctgcgaatgc ttggtttcaa tatcattggg300tcgcttataa tagccgctgt tatcaacctg acccttagct atgccactct tccggggtgg360ttaccttcac ctttcttccc tatatacata cacaacatac acaagtcaaa gcatggaagt420gattcaaaaa catatgacaa tgaaggaagg tttatgccgg tgaatcttga gttgatattt480agcaaatatg cgaaaacctt gccagacaag ttgagtcttg gagaactatg ggagatgaca540gaaggaaacc gtgacgcttg ggacattttt ggatggatcg caggcaaaat agagtgggga600ctgttgtact tgctagcaag ggatgaagaa gggtttttgt caaaagaagc tattaggcgg660tgtttcgatg gaagcttgtt cgagtactgt gccaaaatct acgctggtat cagtgaagac720aagacagcat actactaa 738<210>142<211>1047<212>DNA<213>Sesamum indicum<400>142atggatctaa tccacacttt cctcaactta atagctcccc ctttcacctt cttcttcctt 60ctctttttct tgccaccctt ccagattttc aagttcttcc tttcaatctt gggcaccctt120ttcagcgagg atgtcgctgg aaaagtcgtc gtcatcaccg gcgcctcctc cggcatcggc180gaaagtcttg cttacgagta tgctaagaga ggggcgtgct tggtgcttgc tgcaagaagg240gaaaggagtc ttcaagaagt ggccgaaagg gcgcgcgatt tggggtcgcc ggacgtcgtg300gtggtccggg ccgatgtttc gaaggcggag gactgcagga aggttgttga tcagactatg360aatcgctttg gaagattgga tcacctggtc aataacgctg gaattatgtc agtttcaatg420ctggaagaag ttgaagatat tactggttac agagaaacta tggatatcaa cttctggggc480
tatgtgtata tgacccgatt tgccgcccca taccttagga atagcagagg ccgaattgtt540gtactttctt catccagttc ttggatgcct actccgagga tgagttttta caatgcaagc600aaagcggcga tttcacaatt ttttgagaca ctgcgggtgg aattcggccc cgatataggc660ataacccttg tgactccagg attcatagaa tctgaactta cccaaggcaa attctacaat720gctggcgaac gtgtaattga tcaggacatg agagatgtac aagtgagcac gactccaatc780ctgagggtgg aaagtgcggc aaggtcaatc gtgaggagcg cgatccgtgg agaaagatac840gtgacagagc cggcctggtt tagggttact tattggtgga agctattctg ccctgaggtg900atggagtggg tatttagact gatgtacttg gccagcccgg gtgagccgga gaaggaaacg960tttggcaaga aggttttgga ttacacagga gtgaagtcct tgctttaccc ggaaaccgtg1020caagttccgg agcccaagaa tgattaa1047<210>143<211>108<212>DNA<213>Artificial Sequence<220>
<223>klip8<400>143atggctgaga tcacccgcat tcctctctac aaaggtaagt ctctccgtaa ggcgctgaag 60gaacatggac ttctagaaga cttcttgcag aaacaacagt atggcatc 108<210>144<211>4233<212>DNA<213>Artificial Sequence<220>
<223>Apo10<400>144gaattcattg tactcccagt atcattatag tgaaagtttt ggctctctcg ccggtggttt 60tttacctcta tttaaagggg ttttccacct aaaaattctg gtatcattct cactttactt120gttactttaa tttctcataa tctttggttg aattatcacg cttccgcaca cgatatccct180acaaatttat tatttgttaa acattttcaa accgcataaa attttatgaa gtcccgtcta240tctttaatga gtctaacatt ttcatattga aatatataat ttacttaatt ttagcgttgg300tagaaagcat aaagatttat tcttattctt cttcatataa atgtttaata tacaatataa360acaaattctt taccttaaga aggatttccc attttatatt ttaaaaatat atttatcaaa420
tatttttcaa ccacgtaaat ctcataatat aagttgtttc aaaagtaata aaatttaact 480ccataatttt tttattcgac tgatcttaaa gcaacaccca gtgacacaac tagccatttt 540tttctttgaa taaaaaaatc caattatcat tgtatttttt ttatacaatg aaaatttcac 600caaacaatca tttgtggtat ttctgaagca agtcatgtta tgcaaaatct ataattccca 660tttgacacta cggaagtaac tgaagatctg cttttacatg cgagacacat cttctaaagt 720aattttaata atagttacta tattcaagat ttcatatatc aaatactcaa tattacttct 780aaaaaattaa ttagatataa ttaaaatatt acttttttaa ttttaagttt aattgttgaa 840tttgtgctat tgatttatta ttctactatg tttaaattgt tttatagata gtttaaagta 900aatataagta atgtagtaga gtgttagagt gttaccctaa accataaact ataacattta 960tggtggacta attttcatat atttcttatt gcttttacct tttcttggta tgtaagtccg1020taactagaat tacagtgggt tgccagacac tctgtggtct tttggttcat gcatgggtct1080tgcgcaagaa aaagacaaag aacaaagaaa aaagacaaaa cagagagaca aaacgcaatc1140acacaccaac tcaaattagt cactggctga tcaagatcgc cgcgtccatg tatgtctaaa1200tgccatgcaa agcaacacgt gcttaacatg cactttaaat ggctcaccca tctcaaccca1260cacacaaaca cattgccttt ttcttcatca tcaccacaac cacctgtata tattcattct1320cttccgccac ctcaatttct tcacttcaac acacgtcaac ctgcatatgc gtgtcatccc1380atgcccaaat ctccatgcat gttccaacca ccttctctct tatataatac ctataaatac1440ctcaatatca ctcacttctt tcatcatcca tccatccaga gtactactac tctactacta1500taatacccca acccaactca tattcaatac tactctacca tggatgaacc cccccagagc1560ccctgggatc gagtgaagga cctggccact gtgtacgtgg atgtgctcaa agacagcggc1620agagactatg tgtcccagtt tgaggctccg ccttgggaaa acagctaaac ctaaagctcc1680ttgacaactg ggacagcgtg acctccacct tcagcaagct gcgcgaacag ctcggccctg1740tacccaggag ttctgggata acctggaaaa ggagacagag ggcctgaggc aggagatgag1800caaggatctg gaggaggtga aggccaaggt gcagccctac tggacgactt ccagaagaag1860tggcaggagg agatggagct ctaccgccag aaggtggagc cgctgcgcgc agagctccaa1920gagggcgcgc gccagaagcg cacgagctgc aagagaagct gagcccactg ggcgaggaga1980tgcgcgaccg cgcgcgcgcc catgtggacg cgctgcgcac gcatctggcc ccctacagga2040cgagctgcgc cagcgcttgg ccgcgcgcct tgaggctctc aaggagaacg gcggcgccag2100actggccgag taccacgcca aggccaccga gcatctggca cgctcagcga gaaggccaag2160cccgcgctcg aggacctccg ccaaggcctg ctgcccgtgc tggagagctt caaggtcagc2220
ttcctgagcg ctctcgggag tacactaaga agctcaacac ccaggggatc cccttggcta2280gtaaaggaga agaacttttc actggagttg tcccaattct tgttgaatta gatgggatgt2340taatgggcac aaattttctg tcagtggaga gggtgaaggt gatgctacat acggaaagct2400tacccttaaa tttatttgca ctactggaaa actactgttc cttggccaac acttgtcact2460actttctctt atggtgttca atgcttttca agatacccag atcatatgaa gcggcacgac2520ttcttcaaga gcgcatgcct gagggatacg tgcaggagag gaccatctct ttcaaggacg2580acgggaacta caagacacgt gctgaagtca agtttgaggg agacaccctc gtaacaggat2640cgagcttaag ggaatcgatt tcaaggagga cggaaacatc ctcggccaca agttggaata2700caactacaac tcccacaacg tatacatcac gcagacaaac aaaagaatgg aatcaaagct2760aacttcaaaa ttagacacaa cattgaagat ggaagcgttc aactagcaga ccattatcaa2820caaaatactc aattggcgat ggccctgtcc ttttaccaga caaccattac ctgtccacac2880aatctgccct ttcgaaagat cccaacgaaa agagagacca catggtcctc ttgagtttgt2940aacagctgct gggattacac atggcatgga tgaactatac aaataagtca tgactgcagt3000ctagatttaa atgcaagctt aaataagttg aactaaaatg catgtaggtg taagagctca3060tggagagcat ggaatattgt atccgaccat gtaacagtat aataactgag ctccatctca3120cttcttctat gaataaacaa aggatgttat gatatattaa cactctatct atgcacctta3180ttgttctatg ataaatttcc tcttattatt ataaatcatc tgaatcggac ggcttatgga3240atgcttcaaa tagtacaaaa acaaatgtgt actataagac tttctaaaca attctaactt3300tagcattgtg aacgagacat aagtgtaaga agacataaca attataatgg aagaagtttg3360tctccattta tatattatat attacccact tatgtattat attaggatgt taaggagaca3420taacaattat aaagagagaa gtttgtatcc atttatatat tatatactac ccatttatat3480attatactta tccacttatt taatgtcttt ataaggtttg atccagatat ttctaatatt3540ttagttgata tgtatatgaa aaggtactat ttgaactctc ttactctgta taaaggttgg3600atcatcctta aagtgggtct atttatttta ttgcttctta cagataaaaa aaaaattatg3660agttggtttg ataaaatatt gaaggattta aaataataat aaataataaa taacatataa3720tatatgtata taaatttatt ataatataac atttatctat aaaaaagtaa atattgtcat3780aaatctatac aatcgtttag ccttgctgga acgaatctca atttttaaac gagagtaaac3840atatttgact ttttggttat ttaacaaatt attatttaac actatatgaa attttttttt3900tttatcagca aagaaataaa ataaattaag aaggacaatg gtgtgtccca atccttatac3960
aaccaacttc cacaagaaag tcaagtcaga gacaacaaaa aaacaagcaa aggaaatttt4020taatttgagt tgtcttgttt gctgcataat ttatgcagta aaacactaca cataaccctt4080ttagcagtag agcaatggtt gaccgtgtgc ttagcttctt tattttattt ttttatcagc4140aaagaataaa taaaataaaa tgagacactt cagggatgtt tcaaccctta tacaaaaccc4200caaaaacaag tttcctagca ccctaccaac taa 4233<210>145<211>486<212>PRT<213>Artificial Sequence<220>
<223>Apo10<400>145Met Asp Glu Pro Pro Gln Ser Pro Trp Asp Arg Val Lys Asp Leu Ala1 5 10 15Thr Val Tyr Val Asp Val Leu Lys Asp Ser Gly Arg Asp Tyr Val Ser20 25 30Gln Phe Glu Gly Ser Ala Leu Gly Lys Gln Leu Asn Leu Lys Leu Leu35 40 45Asp Asn Trp Asp Ser Val Thr Ser Thr Phe Ser Lys Leu Arg Glu Gln50 55 60Leu Gly Pro Val Thr Gln Glu Phe Trp Asp Asn Leu Glu Lys Glu Thr65 70 75 80Glu Gly Leu Arg Gln Glu Met Ser Lys Asp Leu Glu Glu Val Lys Ala85 90 95Lys Val Gln Pro Tyr Leu Asp Asp Phe Gln Lys Lys Trp Gln Glu Glu100 105 110Met Glu Leu Tyr Arg Gln Lys Val Glu Pro Leu Arg Ala Glu Leu Gln115 120 125Glu Gly Ala Arg Gln Lys Leu His Glu Leu Gln Glu Lys Leu Ser Pro130 135 140Leu Gly Glu Glu Met Arg Asp Arg Ala Arg Ala His Val Asp Ala Leu145 150 155 160
Arg Thr His Leu Ala Pro Tyr Ser Asp Glu Leu Arg Gln Arg Leu Ala165 170 175Ala Arg Leu Glu Ala Leu Lys Glu Asn Gly Gly Ala Arg Leu Ala Glu180 185 190Tyr His Ala Lys Ala Thr Glu His Leu Ser Thr Leu Ser Glu Lys Ala195 200 205Lys Pro Ala Leu Glu Asp Leu Arg Gln Gly Leu Leu Pro Val Leu Glu210 215 220Ser Phe Lys Val Ser Phe Leu Ser Ala Leu Glu Glu Tyr Thr Lys Lys225 230 235 240Leu Asn Thr Gln Gly Ile Pro Leu Ala Ser Lys Gly Glu Glu Leu Phe245 250 55Thr Gly Val Val Pro Ile Leu Val Glu Leu Asp Gly Asp Val Asn Gly260 265 270His Lys Phe Ser Val Ser Gly Glu Gly Glu Gly Asp Ala Thr Tyr Gly275 280 285Lys Leu Thr Leu Lys Phe Ile Cys Thr Thr Gly Lys Leu Pro Val Pro290 295 300Trp Pro Thr Leu Val Thr Thr Phe Ser Tyr Gly Val Gln Cys Phe Ser305 310 315 320Arg Tyr Pro Asp His Met Lys Arg His Asp Phe Phe Lys Ser Ala Met325 330 335Pro Glu Gly Tyr Val Gln Glu Arg Thr Ile Ser Phe Lys Asp Asp Gly340 345 350Asn Tyr Lys Thr Arg Ala Glu Val Lys Phe Glu Gly Asp Thr Leu Val355 360 365Asn Arg Ile Glu Leu Lys Gly Ile Asp Phe Lys Glu Asp Gly Asn Ile370 375 380Leu Gly His Lys Leu Glu Tyr Asn Tyr Asn Ser His Asn Val Tyr Ile
385 390 395 400Thr Ala Asp Lys Gln Lys Asn Gly Ile Lys Ala Asn Phe Lys Ile Arg405 410 415His Asn Ile Glu Asp Gly Ser Val Gln Leu Ala Asp His Tyr Gln Gln420 425 430Asn Thr Pro Ile Gly Asp Gly Pro Val Leu Leu Pro Asp Asn His Tyr435 440 445Leu Ser Thr Gln Ser Ala Leu Ser Lys Asp Pro Asn Glu Lys Arg Asp450 455 460His Met Val Leu Leu Glu Phe Val Thr Ala Ala Gly Ile Thr His Gly465 470 475 480Met Asp Glu Leu Tyr Lys485<210>146<211>22<212>DNA<213>Artificial Sequence<220>
<223>forward primer 1186<400>146ggatcccctt ggctagtaaa gg 22<210>147<211>40<212>DNA<213>Artificial Sequence<220>
<223>reverse primer 1187<400>147aagctttcta gactgcagtc atgacttatt tgtatagttc 40<210>148<211>30<212>DNA<213>Artificial Sequence<220>
<223>forward primer 1190
<400>148ccatggggcg gcatttctgg cagcaagatg 30<210>149<211>29<212>DNA<213>Artificial Sequence<220>
<223>reverse primer 1189<400>149ggatcccctg ggtgttgagc ttcttagtg 29<210>150<211>4285<212>DNA<213>Artificial Sequence<220>
<223>Apo 11<400>150gaattcattg tactcccagt atcattatag tgaaagtttt ggctctctcg ccggtggttt 60tttacctcta tttaaagggg ttttccacct aaaaattctg gtatcattct cactttactt 120gttactttaa tttctcataa tctttggttg aaattatcac gcttccgcac acgatatccc 180tacaaattta ttatttgtta aacattttca aaccgcataa aattttatga agtcccgtct 240atctttaatg tagtctaaca ttttcatatt gaaatatata atttacttaa ttttagcgtt 300ggtagaaagc ataaagattt attcttattc ttcttcatat aaatgtttaa tatacaatat 360aaacaaattc tttaccttaa gaaggatttc ccattttata ttttaaaaat atatttatca 420aatatttttc aaccacgtaa atctcataat aataagttgt ttcaaaagta ataaaattta 480actccataat ttttttattc gactgatctt aaagcaacac ccagtgacac aactagccat 540ttttttcttt gaataaaaaa atccaattat cattgtattt tttttataca atgaaaattt 600caccaaacaa tcatttgtgg tatttctgaa gcaagtcatg ttatgcaaaa ttctataatt 660cccatttgac actacggaag taactgaaga tctgctttta catgcgagac acatcttcta 720aagtaatttt aataatagtt actatattca agatttcata tatcaaatac tcaatattac 780ttctaaaaaa ttaattagat ataattaaaa tattactttt ttaattttaa gtttaattgt 840tgaatttgtg actattgatt tattattcta ctatgtttaa attgttttat agatagttta 900aagtaaatat aagtaatgta gtagagtgtt agagtgttac cctaaaccat aaactataac 960atttatggtg gactaatttt catatatttc ttattgcttt taccttttct tggtatgtaa1020
gtccgtaact agaattacag tgggttgcca tgacactctg tggtcttttg gttcatgcat1080gggtcttgcg caagaaaaag acaaagaaca aagaaaaaag acaaaacaga gagacaaaac1140gcaatcacac aaccaactca aattagtcac tggctgatca agatcgccgc gtccatgtat1200gtctaaatgc catgcaaagc aacacgtgct taacatgcac tttaaatggc tcacccatct1260caacccacac acaaacacat tgcctttttc ttcatcatca ccacaaccac ctgtatatat1320tcattctctt ccgccacctc aatttcttca cttcaacaca cgtcaacctg catatgcgtg1380tcatcccatg cccaaatctc catgcatgtt ccaaccacct tctctcttat ataataccta1440taaatacctc taatatcact cacttctttc atcatccatc catccagagt actactactc1500tactactata ataccccaac ccaactcata ttcaatacta ctctaccatg gggcggcatt1560tctggcagca agatgaaccc ccccagagcc cctgggatcg agtgaaggac ctggccactg1620tgtacgtgga tgtgctcaaa gacagcggca gagactatgt gtcccagttt gaaggctccg1680ccttgggaaa acagctaaac ctaaagctcc ttgacaactg ggacagcgtg acctccacct1740tcagcaagct gcgcgaacag ctcggccctg tgacccagga gttctgggat aacctggaaa1800aggagacaga gggcctgagg caggagatga gcaaggatct ggaggaggtg aaggccaagg1860tgcagcccta cctggacgac ttccagaaga agtggcagga ggagatggag ctctaccgcc1920agaaggtgga gccgctgcgc gcagagctcc aagagggcgc gcgccagaag ctgcacgagc1980tgcaagagaa gctgagccca ctgggcgagg agatgcgcga ccgcgcgcgc gcccatgtgg2040acgcgctgcg cacgcatctg gccccctaca gcgacgagct gcgccagcgc ttggccgcgc2100gccttgaggc tctcaaggag aacggcggcg ccagactggc cgagtaccac gccaaggcca2160ccgagcatct gagcacgctc agcgagaagg ccaagcccgc gctcgaggac ctccgccaag2220gcctgctgcc cgtgctggag agcttcaagg tcagcttcct gagcgctctc gaggagtaca2280ctaagaagct caacacccag gggatcccct tggctagtaa aggagaagaa cttttcactg2340gagttgtccc aattcttgtt gaattagatg gtgatgttaa tgggcacaaa ttttctgtca2400gtggagaggg tgaaggtgat gctacatacg gaaagcttac ccttaaattt atttgcacta2460ctggaaaact acctgttcct tggccaacac ttgtcactac tttctcttat ggtgttcaat2520gcttttcaag atacccagat catatgaagc ggcacgactt cttcaagagc gccatgcctg2580agggatacgt gcaggagagg accatctctt tcaaggacga cgggaactac aagacacgtg2640ctgaagtcaa gtttgaggga gacaccctcg tcaacaggat cgagcttaag ggaatcgatt2700tcaaggagga cggaaacatc ctcggccaca agttggaata caactacaac tcccacaacg2760tatacatcac ggcagacaaa caaaagaatg gaatcaaagc taacttcaaa attagacaca2820
acattgaaga tggaagcgtt caactagcag accattatca acaaaatact ccaattggcg2880atggccctgt ccttttacca gacaaccatt acctgtccac acaatctgcc ctttcgaaag2940atcccaacga aaagagagac cacatggtcc ttcttgagtt tgtaacagct gctgggatta3000cacatggcat ggatgaacta tacaaataag tcatgactgc agtctagatt taaatgcaag3060cttaaataag tatgaactaa aatgcatgta ggtgtaagag ctcatggaga gcatggaata3120ttgtatccga ccatgtaaca gtataataac tgagctccat ctcacttctt ctatgaataa3180acaaaggatg ttatgatata ttaacactct atctatgcac cttattgttc tatgataaat3240ttcctcttat tattataaat catctgaatc gtgacggctt atggaatgct tcaaatagta3300caaaaacaaa tgtgtactat aagactttct aaacaattct aactttagca ttgtgaacga3360gacataagtg ttaagaagac ataacaatta taatggaaga agtttgtctc catttatata3420ttatatatta cccacttatg tattatatta ggatgttaag gagacataac aattataaag3480agagaagttt gtatccattt atatattata tactacccat ttatatatta tacttatcca3540cttatttaat gtctttataa ggtttgatcc atgatatttc taatatttta gttgatatgt3600atatgaaaag gtactatttg aactctctta ctctgtataa aggttggatc atccttaaag3660tgggtctatt taattttatt gcttcttaca gataaaaaaa aaattatgag ttggtttgat3720aaaatattga aggatttaaa ataataataa ataataaata acatataata tatgtatata3780aatttattat aatataacat ttatctataa aaaagtaaat attgtcataa atctatacaa3840tcgtttagcc ttgctggaac gaatctcaat tatttaaacg agagtaaaca tatttgactt3900tttggttatt taacaaatta ttatttaaca ctatatgaaa tttttttttt ttatcagcaa3960agaaataaaa ttaaattaag aaggacaatg gtgtgtccca atccttatac aaccaacttc4020cacaagaaag tcaagtcaga gacaacaaaa aaacaagcaa aggaaatttt ttaatttgag4080ttgtcttgtt tgctgcataa tttatgcagt aaaacactac acataaccct tttagcagta4140gagcaatggt tgaccgtgtg cttagcttct tttattttat ttttttatca gcaaagaata4200aataaaataa aatgagacac ttcagggatg tttcaaccct tatacaaaac cccaaaaaca4260agtttcctag caccctacca actaa 4285<210>151<211>493<212>PRT<213>Artificial Sequence<220>
<223>Apo11
<400>151Met Gly Arg His Phe Trp Gln Gln Asp Glu Pro Pro Gln Ser Pro Trp1 5 10 15Asp Arg Val Lys Asp Leu Ala Thr Val Tyr Val Asp Val Leu Lys Asp20 25 30Ser Gly Arg Asp Tyr Val Ser Gln Phe Glu Gly Ser Ala Leu Gly Lys35 40 45Gln Leu Asn Leu Lys Leu Leu Asp Asn Trp Asp Ser Val Thr Ser Thr50 55 60Phe Ser Lys Leu Arg Glu Gln Leu Gly Pro Val Thr Gln Glu Phe Trp65 70 75 80Asp Asn Leu Glu Lys Glu Thr Glu Gly Leu Arg Gln Glu Met Ser Lys85 90 95Asp Leu Glu Glu Val Lys Ala Lys Val Gln Pro Tyr Leu Asp Asp Phe100 105 110Gln Lys Lys Trp Gln Glu Glu Met Glu Leu Tyr Arg Gln Lys Val Glu115 120 125Pro Leu Arg Ala Glu Leu Gln Glu Gly Ala Arg Gln Lys Leu His Glu130 135 140Leu Gln Glu Lys Leu Ser Pro Leu Gly Glu Glu Met Arg Asp Arg Ala145 150 155 160Arg Ala His Val Asp Ala Leu Arg Thr His Leu Ala Pro Tyr Ser Asp165 170 175Glu Leu Arg Gln Arg Leu Ala Ala Arg Leu Glu Ala Leu Lys Glu Asn180 185 90Gly Gly Ala Arg Leu Ala Glu Tyr His Ala Lys Ala Thr Glu His Leu195 200 205Ser Thr Leu Ser Glu Lys Ala Lys Pro Ala Leu Glu Asp Leu Arg Gln210 215 220
Gly Leu Leu Pro Val Leu Glu Ser Phe Lys Val Ser Phe Leu Ser Ala225 230 235 240Leu Glu Glu Tyr Thr Lys Lys Leu Asn Thr Gln Gly Ile Pro Leu Ala245 250 255Ser Lys Gly Glu Glu Leu Phe Thr Gly Val Val Pro Ile Leu Val Glu260 265 270Leu Asp Gly Asp Val Asn Gly His Lys Phe Ser Val Ser Gly Glu Gly275 280 285Glu Gly Asp Ala Thr Tyr Gly Lys Leu Thr Leu Lys Phe Ile Cys Thr290 295 300Thr Gly Lys Leu Pro Val Pro Trp Pro Thr Leu Val Thr Thr Phe Ser305 310 315 320Tyr Gly Val Gln Cys Phe Ser Arg Tyr Pro Asp His Met Lys Arg His325 330 335Asp Phe Phe Lys Ser Ala Met Pro Glu Gly Tyr Val Gln Glu Arg Thr340 345 350Ile Ser Phe Lys Asp Asp Gly Asn Tyr Lys Thr Arg Ala Glu Val Lys355 360 365Phe Glu Gly Asp Thr Leu Val Asn Arg Ile Glu Leu Lys Gly Ile Asp370 375 380Phe Lys Glu Asp Gly Asn Ile Leu Gly His Lys Leu Glu Tyr Asn Tyr385 390 395 400Asn Ser His Asn Val Tyr Ile Thr Ala Asp Lys Gln Lys Asn Gly Ile405 410 415Lys Ala Asn Phe Lys Ile Arg His Asn Ile Glu Asp Gly Ser Val Gln420 425 430Leu Ala Asp His Tyr Gln Gln Asn Thr Pro Ile Gly Asp Gly Pro Val435 440 445Leu Leu Pro Asp Asn His Tyr Leu Ser Thr Gln Ser Ala Leu Ser Lys450 455 460
Asp Pro Asn Glu Lys Arg Asp His Met Val Leu Leu Glu Phe Val Thr465 470 475 480Ala Ala Gly Ile Thr His Gly Met Asp Glu Leu Tyr Lys485 490<210>152<211>28<212>DNA<213>Artificial Sequence<220>
<223>forward primer 1191<400>152ccatggatga acccccccag agcccctg 28<210>153<211>5023<212>DNA<213>Artificial Sequence<220>
<223>Apo12<400>153gaattcattg tactcccagt atcattatag tgaaagtttt ggctctctcg ccggtggttt 60tttacctcta tttaaagggg ttttccacct aaaaattctg gtatcattct cactttactt120gttactttaa tttctcataa tctttggttg aaattatcac gcttccgcac acgatatccc180tacaaattta ttatttgtta aacattttca aaccgcataa aattttatga agtcccgtct240atctttaatg tagtctaaca ttttcatatt gaaatatata atttacttaa ttttagcgtt300ggtagaaagc ataaagattt attcttattc ttcttcatat aaatgtttaa tatacaatat360aaacaaattc tttaccttaa gaaggatttc ccattttata ttttaaaaat atatttatca420aatatttttc aaccacgtaa atctcataat aataagttgt ttcaaaagta ataaaattta480actccataat ttttttattc gactgatctt aaagcaacac ccagtgacac aactagccat540ttttttcttt gaataaaaaa atccaattat cattgtattt tttttataca atgaaaattt600caccaaacaa tcatttgtgg tatttctgaa gcaagtcatg ttatgcaaaa ttctataatt660cccatttgac actacggaag taactgaaga tctgctttta catgcgagac acatcttcta720aagtaatttt aataatagtt actatattca agatttcata tatcaaatac tcaatattac780ttctaaaaaa ttaattagat ataattaaaa tattactttt ttaattttaa gtttaattgt840tgaatttgtg actattgatt tattattcta ctatgtttaa attgttttat agatagttta900
aagtaaatat aagtaatgta gtagagtgtt agagtgttac cctaaaccat aaactataac 960atttatggtg gactaatttt catatatttc ttattgcttt taccttttct tggtatgtaa1020gtccgtaact agaattacag tgggttgcca tgacactctg tggtcttttg gttcatgcat1080gggtcttgcg caagaaaaag acaaagaaca aagaaaaaag acaaaacaga gagacaaaac1140gcaatcacac aaccaactca aattagtcac tggctgatca agatcgccgc gtccatgtat1200gtctaaatgc catgcaaagc aacacgtgct taacatgcac tttaaatggc tcacccatct1260caacccacac acaaacacat tgcctttttc ttcatcatca ccacaaccac ctgtatatat1320tcattctctt ccgccacctc aatttcttca cttcaacaca cgtcaacctg catatgcgtg1380tcatcccatq cccaaatctc catgcatgtt ccaaccacct tctctcttat ataataccta1440taaatacctc taatatcact cacttctttc atcatccatc catccagagt actactactc1500tactactata ataccccaac ccaactcata ttcaatacta ctctactatg gcggatacag1560ctagaggaac ccatcacgat atcatcggca gagaccagta cccgatgatg ggccgagacc1620gagaccagta ccagatgtcc ggacgaggat ctgactactc caagtctagg cagattgcta1680aagctgcaac tgctgtcaca gctggtggtt ccctccttgt tctctccagc cttacccttg1740ttggaactgt catagctttg actgttgcaa cacctctgct cgttatcttc agcccaatcc1800ttgtcccggc tctcatcaca gttgcactcc tcatcaccgg ttttctttcc tctggagggt1860ttggcattgc cgctataacc gttttctctt ggatttacaa gtaagcacac atttatcatc1920ttacttcata attttgtgca atatgtgcat gcatgtgttg agccagtagc tttggatcaa1980tttttttggt agaataacaa atgtaacaat aagaaattgc aaattctagg gaacatttgg2040ttaactaaat acgaaatttg acctagctag cttgaatgtg tctgtgtata tcatctatat2100aggtaaaatg cttggtatga tacctattga ttgtgaatag gtacgcaacg ggagagcacc2160cacagggatc agacaagttg gacagtgcaa ggatgaagtt gggaagcaaa gctcaggatc2220tgaaagacag agctcagtac tacggacagc aacatactgg tggggaacat gaccgtgacc2280gtactcgtgg tggccagcac actaccatgg atgaaccccc ccagagcccc tgggatcgag2340tgaaggacct ggccactgtg tacgtggatg tgctcaaaga cagcggcaga gactatgtgt2400cccagtttga aggctccgcc ttgggaaaac agctaaacct aaagctcctt gacaactggg2460acagcgtgac ctccaccttc agcaagctgc gcgaacagct cggccctgtg acccaggagt2520tctgggataa cctggaaaag gagacagagg gcctgaggca ggagatgagc aaggatctgg2580aggaggtgaa ggccaaggtg cagccctacc tggacgactt ccagaagaag tggcaggagg2640
agatggagct ctaccgccag aaggtggagc cgctgcgcgc agagctccaa gagggcgcgc2700gccagaagct gcacgagctg caagagaagc tgagcccact gggcgaggag atgcgcgacc2760gcgcgcgcgc ccatgtggac gcgctgcgca cgcatctggc cccctacagc gacgagctgc2820gccagcgctt ggccgcgcgc cttgaggctc tcaaggagaa cggcggcgcc agactggccg2880agtaccacgc caaggccacc gagcatctga gcacgctcag cgagaaggcc aagcccgcgc2940tcgaggacct ccgccaaggc ctgctgcccg tgctggagag cttcaaggtc agcttcctga3000gcgctctcga ggagtacact aagaagctca acacccaggg gatccccttg gctagtaaag3060gagaagaact tttcactgga gttgtcccaa ttcttgttga attagatggt gatgttaatg3120ggcacaaatt ttctgtcagt ggagagggtg aaggtgatgc tacatacgga aagcttaccc3180ttaaatttat ttgcactact ggaaaactac ctgttccttg gccaacactt gtcactactt3240tctcttatgg tgttcaatgc ttttcaagat acccagatca tatgaagcgg cacgacttct3300tcaagagcgc catgcctgag ggatacgtgc aggagaggac catctctttc aaggacgacg3360ggaactacaa gacacgtgct gaagtcaagt ttgagggaga caccctcgtc aacaggatcg3420agcttaaggg aatcgatttc aaggaggacg gaaacatcct cggccacaag ttggaataca3480actacaactc ccacaacgta tacatcacgg cagacaaaca aaagaatgga atcaaagcta3540acttcaaaat tagacacaac attgaagatg gaagcgttca actagcagac cattatcaac3600aaaatactcc aattggcgat ggccctgtcc ttttaccaga caaccattac ctgtccacac3660aatctgccct ttcgaaagat cccaacgaaa agagagacca catggtcctt cttgagtttg3720taacagctgc tgggattaca catggcatgg atgaactata caaataagtc atgactgcag3780tctagattta aatgcaagct taaataagta tgaactaaaa tgcatgtagg tgtaagagct3840catggagagc atggaatatt gtatccgacc atgtaacagt ataataactg agctccatct3900cacttcttct atgaataaac aaaggatgtt atgatatatt aacactctat ctatgcacct3960tattgttcta tgataaattt cctcttatta ttataaatca tctgaatcgt gacggcttat4020ggaatgcttc aaatagtaca aaaacaaatg tgtactataa gactttctaa acaattctaa4080ctttagcatt gtgaacgaga cataagtgtt aagaagacat aacaattata atggaagaag4140tttgtctcca tttatatatt atatattacc cacttatgta ttatattagg atgttaagga4200gacataacaa ttataaagag agaagtttgt atccatttat atattatata ctacccattt4260atatattata cttatccact tatttaatgt ctttataagg tttgatccat gatatttcta4320atattttagt tgatatgtat atgaaaaggt actatttgaa ctctcttact ctgtataaag4380gttggatcat ccttaaagtg ggtctattta attttattgc ttcttacaga taaaaaaaaa4440
attatgagtt ggtttgataa aatattgaag gatttaaaat aataataaat aataaataac4500atataatata tgtatataaa tttattataa tataacattt atctataaaa aagtaaatat4560tgtcataaat ctatacaatc gtttagcctt gctggaacga atctcaatta tttaaacgag4620agtaaacata tttgactttt tggttattta acaaattatt atttaacact atatgaaatt4680tttttttttt atcagcaaag aaataaaatt aaattaagaa ggacaatggt gtgtcccaat4740ccttatacaa ccaacttcca caagaaagtc aagtcagaga caacaaaaaa acaagcaaag4800gaaatttttt aatttgagtt gtcttgtttg ctgcataatt tatgcagtaa aacactacac4860ataacccttt tagcagtaga gcaatggttg accgtgtgct tagcttcttt tattttattt4920ttttatcagc aaagaataaa taaaataaaa tgagacactt cagggatgtt tcaaccctta4980tacaaaaccc caaaaacaag tttcctagca ccctaccaac taa 5023<210>154<211>659<212>PRT<213>Artificial Sequence<220>
<223>Apo12<400>154Met Ala Asp Thr Ala Arg Gly Thr His His Asp Ile Ile Gly Arg Asp1 5 10 15Gln Tyr Pro Met Met Gly Arg Asp Arg Asp Gln Tyr Gln Met Ser Gly20 25 30Arg Gly Ser Asp Tyr Ser Lys Ser Arg Gln Ile Ala Lys Ala Ala Thr35 40 45Ala Val Thr Ala Gly Gly Ser Leu Leu Val Leu Ser Ser Leu Thr Leu50 55 60Val Gly Thr Val Ile Ala Leu Thr Val Ala Thr Pro Leu Leu Val Ile65 70 75 80Phe Ser Pro Ile Leu Val Pro Ala Leu Ile Thr Val Ala Leu Leu Ile85 90 95Thr Gly Phe Leu Ser Ser Gly Gly Phe Gly Ile Ala Ala Ile Thr Val100 105 110
Phe Ser Trp Ile Tyr Lys Tyr Ala Thr Gly Glu His Pro Gln Gly Ser115 120 125Asp Lys Leu Asp Ser Ala Arg Met Lys Leu Gly Ser Lys Ala Gln Asp130 135 140Leu Lys Asp Arg Ala Gln Tyr Tyr Gly Gln Gln His Thr Gly Gly Glu145 150 155 160His Asp Arg Asp Arg Thr Arg Gly Gly Gln His Thr Thr Met Asp Glu165 170 175Pro Pro Gln Ser Pro Trp Asp Arg Val Lys Asp Leu Ala Thr Val Tyr180 185 190Val Asp Val Leu Lys Asp Ser Gly Arg Asp Tyr Val Ser Gln Phe Glu195 200 205Gly Ser Ala Leu Gly Lys Gln Leu Asn Leu Lys Leu Leu Asp Asn Trp210 215 220Asp Ser Val Thr Ser Thr Phe Ser Lys Lau Arg Glu Gln Leu Gly Pro225 230 235 240Val Thr Gln Glu Phe Trp Asp Asn Leu Glu Lys Glu Thr Glu Gly Leu245 250 255Arg Gln Glu Met Ser Lys Asp Leu Glu Glu Val Lys Ala Lys Val Gln260 265 270Pro Tyr Leu Asp Asp Phe Gln Lys Lys Trp Gln Glu Glu Met Glu Leu275 280 285Tyr Arg Gln Lys Val Glu Pro Leu Arg Ala Glu Leu Gln Glu Gly Ala290 295 300Arg Gln Lys Leu His Glu Leu Gln Glu Lys Leu Ser Pro Leu Gly Glu305 310 315 320Glu Met Arg Asp Arg Ala Arg Ala His Val Asp Ala Leu Arg Thr His325 330 335Leu Ala Pro Tyr Ser Asp Glu Leu Arg Gln Arg Leu Ala Ala Arg Leu340 345 350
Glu Ala Leu Lys Glu Asn Gly Gly Ala Arg Leu Ala Glu Tyr His Ala355 360 365Lys Ala Thr Glu His Leu Ser Thr Leu Ser Glu Lys Ala Lys Pro Ala370 375 380Leu Glu Asp Leu Arg Gln Gly Leu Leu Pro Val Leu Glu Ser Phe Lys385 390 395 400Val Ser Phe Leu Ser Ala Leu Glu Glu Tyr Thr Lys Lys Leu Asn Thr405 410 415Gln Gly Ile Pro Leu Ala Ser Lys Gly Glu Glu Leu Phe Thr Gly Val420 425 430Val Pro Ile Leu Val Glu Leu Asp Gly Asp Val Asn Gly His Lys Phe435 440 445Ser Val Ser Gly Glu Gly Glu Gly Asp Ala Thr Tyr Gly Lys Leu Thr450 455 460Leu Lys Phe Ile Cys Thr Thr Gly Lys Leu Pro Val Pro Trp Pro Thr465 470 475 480Leu Val Thr Thr Phe Ser Tyr Gly Val Gln Cys Phe Ser Arg Tyr Pro485 490 495Asp His Met Lys Arg His Asp Phe Phe Lys Ser Ala Met Pro Glu Gly500 505 510Tyr Val Gln Glu Arg Thr Ile Ser Phe Lys Asp Asp Gly Asn Tyr Lys515 520 525Thr Arg Ala Glu Val Lys Phe Glu Gly Asp Thr Leu Val Asn Arg Ile530 535 540Glu Leu Lys Gly Ile Asp Phe Lys Glu Asp Gly Asn Ile Leu Gly His545 550 555 560Lys Leu Glu Tyr Asn Tyr Asn Ser His Asn Val Tyr Ile Thr Ala Asp565 570 575Lys Gln Lys Asn Gly Ile Lys Ala Asn Phe Lys Ile Arg His Asn Ile
580 585 590Glu Asp Gly Ser Val Gln Leu Ala Asp His Tyr Gln Gln Asn Thr Pro595 600 605Ile Gly Asp Gly Pro Val Leu Leu Pro Asp Asn His Tyr Leu Ser Thr610 615 620Gln Ser Ala Leu Ser Lys Asp Pro Asn Glu Lys Arg Asp His Met Val625 630 635 640Leu Leu Glu Phe Val Thr Ala Ala Gly Ile Thr His Gly Met Asp Glu645 50 655Leu Tyr Lys<210>155<211>5044<212>DNA<213>Artificial Sequence<220>
<223>Apo13<400>155gaattcattg tactcccagt atcattatag tgaaagtttt ggctctctcg ccggtggttt 60tttacctcta tttaaagggg ttttccacct aaaaattctg gtatcattct cactttactt120gttactttaa tttctcataa tctttggttg aaattatcac gcttccgcac acgatatccc180tacaaattta ttatttgtta aacattttca aaccgcataa aattttatga agtcccgtct240atctttaatg tagtctaaca ttttcatatt gaaatatata atttacttaa ttttagcgtt300ggtagaaagc ataaagattt attcttattc ttcttcatat aaatgtttaa tatacaatat360aaacaaattc tttaccttaa gaaggatttc ccattttata ttttaaaaat atatttatca420aatatttttc aaccacgtaa atctcataat aataagttgt ttcaaaagta ataaaattta480actccataat ttttttattc gactgatctt aaagcaacac ccagtgacac aactagccat540ttttttcttt gaataaaaaa atccaattat cattgtattt tttttataca atgaaaattt600caccaaacaa tcatttgtgg tatttctgaa gcaagtcatg ttatgcaaaa ttctataatt660cccatttgac actacggaag taactgaaga tctgctttta catgcgagac acatcttcta720aagtaatttt aataatagtt actatattca agatttcata tatcaaatac tcaatattac780ttctaaaaaa ttaattagat ataattaaaa tattactttt ttaattttaa gtttaattgt840
tgaatttgtg actattgatt tattattcta ctatgtttaa attgttttat agatagttta 900aagtaaatat aagtaatgta gtagagtgtt agagtgttac cctaaaccat aaactataac 960atttatggtg gactaatttt catatatttc ttattgcttt taccttttct tggtatgtaa1020gtccgtaact agaattacag tgggttgcca tgacactctg tggtcttttg gttcatgcat1080gggtcttgcg caagaaaaag acaaagaaca aagaaaaaag acaaaacaga gagacaaaac1140gcaatcacac aaccaactca aattagtcac tggctgatca agatcgccgc gtccatgtat1200gtctaaatgc catgcaaagc aacacgtgct taacatgcac tttaaatggc tcacccatct1260caacccacac acaaacacat tgcctttttc ttcatcatca ccacaaccac ctgtatatat1320tcattctctt ccgccacctc aatttcttca cttcaacaca cgtcaacctg catatgcgtg1380tcatcccatg cccaaatctc catgcatgtt ccaaccacct tctctcttat ataataccta1440taaatacctc taatatcact cacttctttc atcatccatc catccagagt actactactc1500tactactata ataccccaac ccaactcata ttcaatacta ctctactatg gcggatacag1560ctagaggaac ccatcacgat atcatcggca gagaccagta cccgatgatg ggccgagacc1620gagaccagta ccagatgtcc ggacgaggat ctgactactc caagtctagg cagattgcta1680aagctgcaac tgctgtcaca gctggtggtt ccctccttgt tctctccagc cttacccttg1740ttggaactgt catagctttg actgttgcaa cacctctgct cgttatcttc agcccaatcc1800ttgtcccggc tctcatcaca gttgcactcc tcatcaccgg ttttctttcc tctggagggt1860ttggcattgc cgctataacc gttttctctt ggatttacaa gtaagcacac atttatcatc1920ttacttcata attttgtgca atatgtgcat gcatgtgttg agccagtagc tttggatcaa1980tttttttggt agaataacaa atgtaacaat aagaaattgc aaattctagg gaacatttgg2040ttaactaaat acgaaatttg acctagctag cttgaatgtg tctgtgtata tcatctatat2100aggtaaaatg cttggtatga tacctattga ttgtgaatag gtacgcaacg ggagagcacc2160cacagggatc agacaagttg gacagtgcaa ggatgaagtt gggaagcaaa gctcaggatc2220tgaaagacag agctcagtac tacggacagc aacatactgg tggggaacat gaccgtgacc2280gtactcgtgg tggccagcac actaccatgg ggcggcattt ctggcagcaa gatgaacccc2340cccagagccc ctgggatcga gtgaaggacc tggccactgt gtacgtggat gtgctcaaag2400acagcggcag agactatgtg tcccagtttg aaggctccgc cttgggaaaa cagctaaacc2460taaagctcct tgacaactgg gacagcgtga cctccacctt cagcaagctg cgcgaacagc2520tcggccctgt gacccaggag ttctgggata acctggaaaa ggagacagag ggcctgaggc2580
aggagatgag caaggatctg gaggaggtga aggccaaggt gcagccctac ctggacgact2640tccagaagaa gtggcaggag gagatggagc tctaccgcca gaaggtggag ccgctgcgcg2700cagagctcca agagggcgcg cgccagaagc tgcacgagct gcaagagaag ctgagcccac2760tgggcgagga gatgcgcgac cgcgcgcgcg cccatgtgga cgcgctgcgc acgcatctgg2820ccccctacag cgacgagctg cgccagcgct tggccgcgcg ccttgaggct ctcaaggaga2880acggcggcgc cagactggcc gagtaccacg ccaaggccac cgagcatctg agcacgctca2940gcgagaaggc caagcccgcg ctcgaggacc tccgccaagg cctgctgccc gtgctggaga3000gcttcaaggt cagcttcctg agcgctctcg aggagtacac taagaagctc aacacccagg3060ggatcccctt ggctagtaaa ggagaagaac ttttcactgg agttgtccca attcttgttg3120aattagatgg tgatgttaat gggcacaaat tttctgtcag tggagagggt gaaggtgatg3180ctacatacgg aaagcttacc cttaaattta tttgcactac tggaaaacta cctgttcctt3240ggccaacact tgtcactact ttctcttatg gtgttcaatg cttttcaaga tacccagatc3300atatgaagcg gcacgacttc ttcaagagcg ccatgcctga gggatacgtg caggagagga3360ccatctcttt caaggacgac gggaactaca agacacgtgc tgaagtcaag tttgagggag3420acaccctcgt caacaggatc gagcttaagg gaatcgattt caaggaggac ggaaacatcc3480tcggccacaa gttggaatac aactacaact cccacaacgt atacatcacg gcagacaaac3540aaaagaatgg aatcaaagct aacttcaaaa ttagacacaa cattgaagat ggaagcgttc3600aactagcaga ccattatcaa caaaatactc caattggcga tggccctgtc cttttaccag3660acaaccatta cctgtccaca caatctgccc tttcgaaaga tcccaacgaa aagagagacc3720acatggtcct tcttgagttt gtaacagctg ctgggattac acatggcatg gatgaactat3780acaaataagt catgactgca gtctagattt aaatgcaagc ttaaataagt atgaactaaa3840atgcatgtag gtgtaagagc tcatggagag catggaatat tgtatccgac catgtaacag3900tataataact gagctccatc tcacttcttc tatgaataaa caaaggatgt tatgatatat3960taacactcta tctatgcacc ttattgttct atgataaatt tcctcttatt attataaatc4020atctgaatcg tgacggctta tggaatgctt caaatagtac aaaaacaaat gtgtactata4080agactttcta aacaattcta actttagcat tgtgaacgag acataagtgt taagaagaca4140taacaattat aatggaagaa gtttgtctcc atttatatat tatatattac ccacttatgt4200attatattag gatgttaagg agacataaca attataaaga gagaagtttg tatccattta4260tatattatat actacccatt tatatattat acttatccac ttatttaatg tctttataag4320gtttgatcca tgatatttct aatattttag ttgatatgta tatgaaaagg tactatttga4380
actctcttac tctgtataaa ggttggatca tccttaaagt gggtctattt aattttattg4440cttcttacag ataaaaaaaa aattatgagt tggtttgata aaatattgaa ggatttaaaa4500taataataaa taataaataa catataatat atgtatataa atttattata atataacatt4560tatctataaa aaagtaaata ttgtcataaa tctatacaat cgtttagcct tgctggaacg4620aatctcaatt atttaaacga gagtaaacat atttgacttt ttggttattt aacaaattat4680tatttaacac tatatgaaat tttttttttt tatcagcaaa gaaataaaat taaattaaga4740aggacaatgg tgtgtcccaa tccttataca accaacttcc acaagaaagt caagtcagag4800acaacaaaaa aacaagcaaa ggaaattttt taatttgagt tgtcttgttt gctgcataat4860ttatgcagta aaacactaca cataaccctt ttagcagtag agcaatggtt gaccgtgtgc4920ttagcttctt ttattttatt tttttatcag caaagaataa ataaaataaa atgagacact4980tcagggatgt ttcaaccctt atacaaaacc ccaaaaacaa gtttcctagc accctaccaa5040ctaa 5044<210>156<211>666<212>PRT<213>Artificial Sequence<220>
<223>Apo13<400>156Met Ala Asp Thr Ala Arg Gly Thr His His Asp Ile Ile Gly Arg Asp1 5 10 15Gln Tyr Pro Met Met Gly Arg Asp Arg Asp Gln Tyr Gln Met Ser Gly20 25 30Arg Gly Ser Asp Tyr Ser Lys Ser Arg Gln Ile Ala Lys Ala Ala Thr35 40 45Ala Val Thr Ala Gly Gly Ser Leu Leu Val Leu Ser Ser Leu Thr Leu50 55 60Val Gly Thr Val Ile Ala Leu Thr Val Ala Thr Pro Leu Leu Val Ile65 70 75 80Phe Ser Pro Ile Leu Val Pro Ala Leu Ile Thr Val Ala Leu Leu Ile85 90 95
Thr Gly Phe Leu Ser Ser Gly Gly Phe Gly Ile Ala Ala Ile Thr Val100 105 110Phe Ser Trp Ile Tyr Lys Tyr Ala Thr Gly Glu His Pro Gln Gly Ser115 120 125Asp Lys Leu Asp Ser Ala Arg Met Lys Leu Gly Ser Lys Ala Gln Asp130 135 140Leu Lys Asp Arg Ala Gln Tyr Tyr Gly Gln Gln His Thr Gly Gly Glu145 150 155 160His Asp Arg Asp Arg Thr Arg Gly Gly Gln His Thr Thr Met Gly Arg165 170 175His Phe Trp Gln Gln Asp Glu Pro Pro Gln Ser Pro Trp Asp Arg Val180 185 190Lys Asp Leu Ala Thr Val Tyr Val Asp Val Leu Lys Asp Ser Gly Arg195 200 205Asp Tyr Val Ser Gln Phe Glu Gly Ser Ala Leu Gly Lys Gln Leu Asn210 215 220Leu Lys Leu Leu Asp Asn Trp Asp Ser Val Thr Ser Thr Phe Ser Lys225 230 235 240Leu Arg Glu Gln Leu Gly Pro Val Thr Gln Glu Phe Trp Asp Asn Leu245 250 255Glu Lys Glu Thr Glu Gly Leu Arg Gln Glu Met Ser Lys Asp Leu Glu260 265 270Glu Val Lys Ala Lys Val Gln Pro Tyr Leu Asp Asp Phe Gln Lys Lys275 280 285Trp Gln Glu Glu Met Glu Leu Tyr Arg Gln Lys Val Glu Pro Leu Arg290 295 300Ala Glu Leu Gln Glu Gly Ala Arg Gln Lys Leu His Glu Leu Gln Glu305 310 315 320Lys Leu Ser Pro Leu Gly Glu Glu Met Arg Asp Arg Ala Arg Ala His325 330 335
Val Asp Ala Leu Arg Thr His Leu Ala Pro Tyr Ser Asp Glu Leu Arg340 345 350Gln Arg Leu Ala Ala Arg Leu Glu Ala Leu Lys Glu Asn Gly Gly Ala355 360 365Arg Leu Ala Glu Tyr His Ala Lys Ala Thr Glu His Leu Ser Thr Leu370 375 380Ser Glu Lys Ala Lys Pro Ala Leu Glu Asp Leu Arg Gln Gly Leu Leu385 390 395 400Pro Val Leu Glu Ser Phe Lys Val Ser Phe Leu Ser Ala Leu Glu Glu405 410 415Tyr Thr Lys Lys Leu Asn Thr Gln Gly Ile Pro Leu Ala Ser Lys Gly420 425 430Glu Glu Leu Phe Thr Gly Val Val Pro Ile Leu Val Glu Leu Asp Gly435 440 445Asp Val Asn Gly His Lys Phe Ser Val Ser Gly Glu Gly Glu Gly Asp450 455 460Ala Thr Tyr Gly Lys Leu Thr Leu Lys Phe Ile Cys Thr Thr Gly Lys465 470 475 480Leu Pro Val Pro Trp Pro Thr Leu Val Thr Thr Phe Ser Tyr Gly Val485 490 495Gln Cys Phe Ser Arg Tyr Pro Asp His Met Lys Arg His Asp Phe Phe500 505 510Lys Ser Ala Met Pro Glu Gly Tyr Val Gln Glu Arg Thr Ile Ser Phe515 520 525Lys Asp Asp Gly Asn Tyr Lys Thr Arg Ala Glu Val Lys Phe Glu Gly530 535 540Asp Thr Leu Val Asn Arg Ile Glu Leu Lys Gly Ile Asp Phe Lys Glu545 550 555 560Asp Gly Asn Ile Leu Gly His Lys Leu Glu Tyr Asn Tyr Asn Ser His
565 570 575Asn Val Tyr Ile Thr Ala Asp Lys Gln Lys Asn Gly Ile Lys Ala Asn580 585 590Phe Lys Ile Arg His Asn Ile Glu Asp Gly Ser Val Gln Leu Ala Asp595 600 605His Tyr Gln Gln Asn Thr Pro Ile Gly Asp Gly Pro Val Leu Leu Pro610 615 620Asp Asn His Tyr Leu Ser Thr Gln Ser Ala Leu Ser Lys Asp Pro Asn625 630 635 640Glu Lys Arg Asp His Met Val Leu Leu Glu Phe Val Thr Ala Ala Gly645 650 655Ile Thr His Gly Met Asp Glu Leu Tyr Lys660 665<210>157<211>4339<212>DNA<213>Artificial Sequence<220>
<223>Apo15<400>157gaattcattg tactcccagt atcattatag tgaaagtttt ggctctctcg ccggtggttt 60tttacctcta tttaaagggg ttttccacct aaaaattctg gtatcattct cactttactt120gttactttaa tttctcataa tctttggttg aaattatcac gcttccgcac acgatatccc180tacaaattta ttatttgtta aacattttca aaccgcataa aattttatga agtcccgtct240atctttaatg tagtctaaca ttttcatatt gaaatatata atttacttaa ttttagcgtt300ggtagaaagc ataaagattt attcttattc ttcttcatat aaatgtttaa tatacaatat360aaacaaattc tttaccttaa gaaggatttc ccattttata ttttaaaaat atatttatca420aatatttttc aaccacgtaa atctcataat aataagttgt ttcaaaagta ataaaattta480actccataat ttttttattc gactgatctt aaagcaacac ccagtgacac aactagccat540ttttttcttt gaataaaaaa atccaattat cattgtattt tttttataca atgaaaattt600caccaaacaa tcatttgtgg tatttctgaa gcaagtcatg ttatgcaaaa ttctataatt660cccatttgac actacggaag taactgaaga tctgctttta catgcgagac acatcttcta720
aagtaatttt aataatagtt actatattca agatttcata tatcaaatac tcaatattac 780ttctaaaaaa ttaattagat ataattaaaa tattactttt ttaattttaa gtttaattgt 840tgaatttgtg actattgatt tattattcta ctatgtttaa attgttttat agatagttta 900aagtaaatat aagtaatgta gtagagtgtt agagtgttac cctaaaccat aaactataac 960atttatggtg gactaatttt catatatttc ttattgcttt taccttttct tggtatgtaa1020gtccgtaact agaattacag tgggttgcca tgacactctg tggtcttttg gttcatgcat1080gggtcttgcg caagaaaaag acaaagaaca aagaaaaaag acaaaacaga gagacaaaac1140gcaatcacac aaccaactca aattagtcac tggctgatca agatcgccgc gtccatgtat1200gtctaaatgc catgcaaagc aacacgtgct taacatgcac tttaaatggc tcacccatct1260caacccacac acaaacacat tgcctttttc ttcatcatca ccacaaccac ctgtatatat1320tcattctctt ccgccacctc aatttcttca cttcaacaca cgtcaacctg catatgcgtg1380tcatcccatg cccaaatctc catgcatgtt ccaaccacct tctctcttat ataataccta1440taaatacctc taatatcact cacttctttc atcatccatc catccagagt actactactc1500tactactata ataccccaac ccaactcata ttcaatacta ctctaccatg aacttcctta1560agtctttccc tttctacgct ttcctttgtt tcggtcaata cttcgttgct gttacgcatg1620ccatggatga acccccccag agcccctggg atcgagtgaa ggacctggcc actgtgtacg1680tggatgtgct caaagacagc ggcagagact atgtgtccca gtttgaaggc tccgccttgg1740gaaaacagct aaacctaaag ctccttgaca actgggacag cgtgacctcc accttcagca1800agctgcgcga acagctcggc cctgtgaccc aggagttctg ggataacctg gaaaaggaga1860cagagggcct gaggcaggag atgagcaagg atctggagga ggtgaaggcc aaggtgcagc1920cctacctgga cgacttccag aagaagtggc aggaggagat ggagctctac cgccagaagg1980tggagccgct gcgcgcagag ctccaagagg gcgcgcgcca gaagctgcac gagctgcaag2040agaagctgag cccactgggc gaggagatgc gcgaccgcgc gcgcgcccat gtggacgcgc2100tgcgcacgca tctggccccc tacagcgacg agctgcgcca gcgcttggcc gcgcgccttg2160aggctctcaa ggagaacggc ggcgccagac tggccgagta ccacgccaag gccaccgagc2220atctgagcac gctcagcgag aaggccaagc ccgcgctcga ggacctccgc caaggcctgc2280tgcccgtgct ggagagcttc aaggtcagct tcctgagcgc tctcgaggag tacactaaga2340agctcaacac ccaggggatc cccttggcta gtaaaggaga agaacttttc actggagttg2400tcccaattct tgttgaatta gatggtgatg ttaatgggca caaattttct gtcagtggag2460
agggtgaagg tgatgctaca tacggaaagc ttacccttaa atttatttgc actactggaa2520aactacctgt tccttggcca acacttgtca ctactttctc ttatggtgtt caatgctttt2580caagataccc agatcatatg aagcggcacg acttcttcaa gagcgccatg cctgagggat2640acgtgcagga gaggaccatc tctttcaagg acgacgggaa ctacaagaca cgtgctgaag2700tcaagtttga gggagacacc ctcgtcaaca ggatcgagct taagggaatc gatttcaagg2760aggacggaaa catcctcggc cacaagttgg aatacaacta caactcccac aacgtataca2820tcacggcaga caaacaaaag aatggaatca aagctaactt caaaattaga cacaacattg2880aagatggaag cgttcaacta gcagaccatt atcaacaaaa tactccaatt ggcgatggcc2940ctgtcctttt accagacaac cattacctgt ccacacaatc tgccctttcg aaagatccca3000acgaaaagag agaccacatg gtccttcttg agtttgtaac agctgctggg attacacatg3060gcatggatga actatacaaa taagtcatga ctgcagtcta gatttaaatg caagcttaaa3120taagtatgaa ctaaaatgca tgtaggtgta agagctcatg gagagcatgg aatattgtat3180ccgaccatgt aacagtataa taactgagct ccatctcact tcttctatga ataaacaaag3240gatgttatga tatattaaca ctctatctat gcaccttatt gttctatgat aaatttcctc3300ttattattat aaatcatctg aatcgtgacg gcttatggaa tgcttcaaat agtacaaaaa3360caaatgtgta ctataagact ttctaaacaa ttctaacttt agcattgtga acgagacata3420agtgttaaga agacataaca attataatgg aagaagtttg tctccattta tatattatat3480attacccact tatgtattat attaggatgt taaggagaca taacaattat aaagagagaa3540gtttgtatcc atttatatat tatatactac ccatttatat attatactta tccacttatt3600taatgtcttt ataaggtttg atccatgata tttctaatat tttagttgat atgtatatga3660aaaggtacta tttgaactct cttactctgt ataaaggttg gatcatcctt aaagtgggtc3720tatttaattt tattgcttct tacagataaa aaaaaaatta tgagttggtt tgataaaata3780ttgaaggatt taaaataata ataaataata aataacatat aatatatgta tataaattta3840ttataatata acatttatct ataaaaaagt aaatattgtc ataaatctat acaatcgttt3900agccttgctg gaacgaatct caattattta aacgagagta aacatatttg actttttggt3960tatttaacaa attattattt aacactatat gaaatttttt ttttttatca gcaaagaaat4020aaaattaaat taagaaggac aatggtgtgt cccaatcctt atacaaccaa cttccacaag4080aaagtcaagt cagagacaac aaaaaaacaa gcaaaggaaa ttttttaatt tgagttgtct4140tgtttgctgc ataatttatg cagtaaaaca ctacacataa cccttttagc agtagagcaa4200tggttgaccg tgtgcttagc ttcttttatt ttattttttt atcagcaaag aataaataaa4260
ataaaatgag acacttcagg gatgtttcaa cccttataca aaaccccaaa aacaagtttc4320ctagcaccct accaactaa 4339<210>158<211>511<212>PRT<213>Artificial Sequence<220>
<223>Apo15<400>158Met Asn Phe Leu Lys Ser Phe Pro Phe Tyr Ala Phe Leu Cys Phe Gly1 5 10 15Gln Tyr Phe Val Ala Val Thr His Ala Met Asp Glu Pro Pro Gln Ser20 25 30Pro Trp Asp Arg Val Lys Asp Leu Ala Thr Val Tyr Val Asp Val Leu35 40 45Lys Asp Ser Gly Arg Asp Tyr Val Ser Gln Phe Glu Gly Ser Ala Leu50 55 60Gly Lys Gln Leu Asn Leu Lys Leu Leu Asp Asn Trp Asp Ser Val Thr65 70 75 80Ser Thr Phe Ser Lys Leu Arg Glu Gln Leu Gly Pro Val Thr Gln Glu85 90 95Phe Trp Asp Asn Leu Glu Lys Glu Thr Glu Gly Leu Arg Gln Glu Met100 105 110Ser Lys Asp Leu Glu Glu Val Lys Ala Lys Val Gln Pro Tyr Leu Asp115 120 125Asp Phe Gln Lys Lys Trp Gln Glu Glu Met Glu Leu Tyr Arg Gln Lys130 135 140Val Glu Pro Leu Arg Ala Glu Leu Gln Glu Gly Ala Arg Gln Lys Leu145 150 155 160His Glu Leu Gln Glu Lys Leu Ser Pro Leu Gly Glu Glu Met Arg Asp165 170 175
Arg Ala Arg Ala His Val Asp Ala Leu Arg Thr His Leu Ala Pro Tyr180 185 190Ser Asp Glu Leu Arg Gln Arg Leu Ala Ala Arg Leu Glu Ala Leu Lys195 200 205Glu Asn Gly Gly Ala Arg Leu Ala Glu Tyr His Ala Lys Ala Thr Glu210 215 220His Leu Ser Thr Leu Ser Glu Lys Ala Lys Pro Ala Leu Glu Asp Leu225 230 235 240Arg Gln Gly Leu Leu Pro Val Leu Glu Ser Phe Lys Val Ser Phe Leu245 250 255Ser Ala Leu Glu Glu Tyr Thr Lys Lys Leu Asn Thr Gln Gly Ile Pro260 265 270Leu Ala Ser Lys Gly Glu Glu Leu Phe Thr Gly Val Val Pro Ile Leu275 280 285Val Glu Leu Asp Gly Asp Val Asn Gly His Lys Phe Ser Val Ser Gly290 295 300Glu Gly Glu Gly Asp Ala Thr Tyr Gly Lys Lau Thr Leu Lys Phe Ile305 310 315 320Cys Thr Thr Gly Lys Leu Pro Val Pro Trp Pro Thr Leu Val Thr Thr325 330 335Phe Ser Tyr Gly Val Gln Cys Phe Ser Arg Tyr Pro Asp His Met Lys340 345 350Arg His Asp Phe Phe Lys Ser Ala Met Pro Glu Gly Tyr Val Gln Glu355 360 365Arg Thr Ile Ser Phe Lys Asp Asp Gly Asn Tyr Lys Thr Arg Ala Glu370 375 380Val Lys Phe Glu Gly Asp Thr Leu Val Asn Arg Ile Glu Leu Lys Gly385 390 395 400Ile Asp Phe Lys Glu Asp Gly Asn Ile Leu Gly His Lys Leu Glu Tyr405 410 415
Asn Tyr Asn Ser His Asn Val Tyr Ile Thr Ala Asp Lys Gln Lys Asn420 425 430Gly Ile Lys Ala Asn Phe Lys Ile Arg His Asn Ile Glu Asp Gly Ser435 440 445Val Gln Leu Ala Asp His Tyr Gln Gln Asn Thr Pro Ile Gly Asp Gly450 455 460Pro Val Leu Leu Pro Asp Asn His Tyr Leu Ser Thr Gln Ser Ala Leu465 470 475 480Ser Lys Asp Pro Asn Glu Lys Arg Asp His Met Val Leu Leu Glu Phe485 490 495Val Thr Ala Ala Gly Ile Thr His Gly Met Asp Glu Leu Tyr Lys500 505 510<210>159<211>4360<212>DNA<213>Artificial Sequence<220>
<223>Apo16<400>159gaattcattg tactcccagt atcattatag tgaaagtttt ggctctctcg ccggtggttt 60tttacctcta tttaaagggg ttttccacct aaaaattctg gtatcattct cactttactt120gttactttaa tttctcataa tctttggttg aaattatcac gcttccgcac acgatatccc180tacaaattta ttatttgtta aacattttca aaccgcataa aattttatga agtcccgtct240atctttaatg tagtctaaca ttttcatatt gaaatatata atttacttaa ttttagcgtt300ggtagaaagc ataaagattt attcttattc ttcttcatat aaatgtttaa tatacaatat360aaacaaattc tttaccttaa gaaggatttc ccattttata ttttaaaaat atatttatca420aatatttttc aaccacgtaa atctcataat aataagttgt ttcaaaagta ataaaattta480actccataat ttttttattc gactgatctt aaagcaacac ccagtgacac aactagccat540ttttttcttt gaataaaaaa atccaattat cattgtattt tttttataca atgaaaattt600caccaaacaa tcatttgtgg tatttctgaa gcaagtcatg ttatgcaaaa ttctataatt660cccatttgac actacggaag taactgaaga tctgctttta catgcgagac acatcttcta720
aagtaatttt aataatagtt actatattca agatttcata tatcaaatac tcaatattac 780ttctaaaaaa ttaattagat ataattaaaa tattactttt ttaattttaa gtttaattgt 840tgaatttgtg actattgatt tattattcta ctatgtttaa attgttttat agatagttta 900aagtaaatat aagtaatgta gtagagtgtt agagtgttac cctaaaccat aaactataac 960atttatggtg gactaatttt catatatttc ttattgcttt taccttttct tggtatgtaa1020gtccgtaact agaattacag tgggttgcca tgacactctg tggtcttttg gttcatgcat1080gggtcttgcg caagaaaaag acaaagaaca aagaaaaaag acaaaacaga gagacaaaac1140gcaatcacac aaccaactca aattagtcac tggctgatca agatcgccgc gtccatgtat1200gtctaaatgc catgcaaagc aacacgtgct taacatgcac tttaaatggc tcacccatct1260caacccacac acaaacacat tgcctttttc ttcatcatca ccacaaccac ctgtatatat1320tcattctctt ccgccacctc aatttcttca cttcaacaca cgtcaacctg catatgcgtg1380tcatcccatg cccaaatctc catgcatgtt ccaaccacct tctctcttat ataataccta1440taaatacctc taatatcact cacttctttc atcatccatc catccagagt actactactc1500tactactata ataccccaac ccaactcata ttcaatacta ctctaccatg aacttcctta1560agtctttccc tttctacgct ttcctttgtt tcggtcaata cttcgttgct gttacgcatg1620ccatggggcg gcatttctgg cagcaagatg aaccccccca gagcccctgg gatcgagtga1680aggacctggc cactgtgtac gtggatgtgc tcaaagacag cggcagagac tatgtgtccc1740agtttgaagg ctccgccttg ggaaaacagc taaacctaaa gctccttgac aactgggaca1800gcgtgacctc caccttcagc aagctgcgcg aacagctcgg ccctgtgacc caggagttct1860gggataacct ggaaaaggag acagagggcc tgaggcagga gatgagcaag gatctggagg1920aggtgaaggc caaggtgcag ccctacctgg acgacttcca gaagaagtgg caggaggaga1980tggagctcta ccgccagaag gtggagccgc tgcgcgcaga gctccaagag ggcgcgcgcc2040agaagctgca cgagctgcaa gagaagctga gcccactggg cgaggagatg cgcgaccgcg2100cgcgcgccca tgtggacgcg ctgcgcacgc atctggcccc ctacagcgac gagctgcgcc2160agcgcttggc cgcgcgcctt gaggctctca aggagaacgg cggcgccaga ctggccgagt2220accacgccaa ggccaccgag catctgagca cgctcagcga gaaggccaag cccgcgctcg2280aggacctccg ccaaggcctg ctgcccgtgc tggagagctt caaggtcagc ttcctgagcg2340ctctcgagga gtacactaag aagctcaaca cccaggggat ccccttggct agtaaaggag2400aagaactttt cactggagtt gtcccaattc ttgttgaatt agatggtgat gttaatgggc2460acaaattttc tgtcagtgga gagggtgaag gtgatgctac atacggaaag cttaccctta2520
aatttatttg cactactgga aaactacctg ttccttggcc aacacttgtc actactttct2580cttatggtgt tcaatgcttt tcaagatacc cagatcatat gaagcggcac gacttcttca2640agagcgccat gcctgaggga tacgtgcagg agaggaccat ctctttcaag gacgacggga2700actacaagac acgtgctgaa gtcaagtttg agggagacac cctcgtcaac aggatcgagc2760ttaagggaat cgatttcaag gaggacggaa acatcctcgg ccacaagttg gaatacaact2820acaactccca caacgtatac atcacggcag acaaacaaaa gaatggaatc aaagctaact2880tcaaaattag acacaacatt gaagatggaa gcgttcaact agcagaccat tatcaacaaa2940atactccaat tggcgatggc cctgtccttt taccagacaa ccattacctg tccacacaat3000ctgccctttc gaaagatccc aacgaaaaga gagaccacat ggtccttctt gagtttgtaa3060cagctgctgg gattacacat ggcatggatg aactatacaa ataagtcatg actgcagtct3120agatttaaat gcaagcttaa ataagtatga actaaaatgc atgtaggtgt aagagctcat3180ggagagcatg gaatattgta tccgaccatg taacagtata ataactgagc tccatctcac3240ttcttctatg aataaacaaa ggatgttatg atatattaac actctatcta tgcaccttat3300tgttctatga taaatttcct cttattatta taaatcatct gaatcgtgac ggcttatgga3360atgcttcaaa tagtacaaaa acaaatgtgt actataagac tttctaaaca attctaactt3420tagcattgtg aacgagacat aagtgttaag aagacataac aattataatg gaagaagttt3480gtctccattt atatattata tattacccac ttatgtatta tattaggatg ttaaggagac3540ataacaatta taaagagaga agtttgtatc catttatata ttatatacta cccatttata3600tattatactt atccacttat ttaatgtctt tataaggttt gatccatgat atttctaata3660ttttagttga tatgtatatg aaaaggtact atttgaactc tcttactctg tataaaggtt3720ggatcatcct taaagtgggt ctatttaatt ttattgcttc ttacagataa aaaaaaaatt3780atgagttggt ttgataaaat attgaaggat ttaaaataat aataaataat aaataacata3840taatatatgt atataaattt attataatat aacatttatc tataaaaaag taaatattgt3900cataaatcta tacaatcgtt tagccttgct ggaacgaatc tcaattattt aaacgagagt3960aaacatattt gactttttgg ttatttaaca aattattatt taacactata tgaaattttt4020tttttttatc agcaaagaaa taaaattaaa ttaagaagga caatggtgtg tcccaatcct4080tatacaacca acttccacaa gaaagtcaag tcagagacaa caaaaaaaca agcaaaggaa4140attttttaat ttgagttgtc ttgtttgctg cataatttat gcagtaaaac actacacata4200acccttttag cagtagagca atggttgacc gtgtgcttag cttcttttat tttatttttt4260
tatcagcaaa gaataaataa aataaaatga gacacttcag ggatgtttca acccttatac4320aaaaccccaa aaacaagttt cctagcaccc taccaactaa 4360<210>160<211>518<212>PRT<213>Artificial Sequence<220>
<223>Apo16<400>160Met Asn Phe Leu Lys Ser Phe Pro Phe Tyr Ala Phe Leu Cys Phe Gly1 5 10 15Gln Tyr Phe Val Ala Val Thr His Ala Met Gly Arg His Phe Trp Gln20 25 30Gln Asp Glu Pro Pro Gln Ser Pro Trp Asp Arg Val Lys Asp Leu Ala35 40 45Thr Val Tyr Val Asp Val Leu Lys Asp Ser Gly Arg Asp Tyr Val Ser50 55 60Gln Phe Glu Gly Ser Ala Leu Gly Lys Gln Leu Asn Leu Lys Leu Leu65 70 75 80Asp Asn Trp Asp Ser Val Thr Ser Thr Phe Ser Lys Leu Arg Glu Gln85 90 95Leu Gly Pro Val Thr Gln Glu Phe Trp Asp Asn Leu Glu Lys Glu Thr100 105 110Glu Gly Leu Arg Gln Glu Met Ser Lys Asp Leu Glu Glu Val Lys Ala115 120 125Lys Val Gln Pro Tyr Leu Asp Asp Phe Gln Lys Lys Trp Gln Glu Glu130 135 140Met Glu Leu Tyr Arg Gln Lys Val Glu Pro Leu Arg Ala Glu Leu Gln145 150 155 160Glu Gly Ala Arg Gln Lys Leu His Glu Leu Gln Glu Lys Leu Ser Pro165 170 175
Leu Gly Glu Glu Met Arg Asp Arg Ala Arg Ala His Val Asp Ala Leu180 185 190Arg Thr His Leu Ala Pro Tyr Ser Asp Glu Leu Arg Gln Arg Leu Ala195 200 205Ala Arg Leu Glu Ala Leu Lys Glu Asn Gly Gly Ala Arg Leu Ala Glu210 215 220Tyr His Ala Lys Ala Thr Glu His Leu Ser Thr Leu Ser Glu Lys Ala225 230 235 240Lys Pro Ala Leu Glu Asp Leu Arg Gln Gly Leu Leu Pro Val Leu Glu245 250 255Ser Phe Lys Val Ser Phe Leu Ser Ala Leu Glu Glu Tyr Thr Lys Lys260 265 270Leu Asn Thr Gln Gly Ile Pro Leu Ala Ser Lys Gly Glu Glu Leu Phe275 280 285Thr Gly Val Val Pro Ile Leu Val Glu Leu Asp Gly Asp Val Asn Gly290 295 300His Lys Phe Ser Val Ser Gly Glu Gly Glu Gly Asp Ala Thr Tyr Gly305 310 315 320Lys Leu Thr Leu Lys Phe Ile Cys Thr Thr Gly Lys Leu Pro Val Pro325 330 335Trp Pro Thr Leu Val Thr Thr Phe Ser Tyr Gly Val Gln Cys Phe Ser340 345 350Arg Tyr Pro Asp His Met Lys Arg His Asp Phe Phe Lys Ser Ala Met355 360 365Pro Glu Gly Tyr Val Gln Glu Arg Thr Ile Ser Phe Lys Asp Asp Gly370 375 380Asn Tyr Lys Thr Arg Ala Glu Val Lys Phe Glu Gly Asp Thr Leu Val385 390 395 400Asn Arg Ile Glu Leu Lys Gly Ile Asp Phe Lys Glu Asp Gly Asn Ile405 410 415
Leu Gly His Lys Leu Glu Tyr Asn Tyr Asn Ser His Asn Val Tyr Ile420 425 430Thr Ala Asp Lys Gln Lys Asn Gly Ile Lys Ala Asn Phe Lys Ile Arg435 440 445His Asn Ile Glu Asp Gly Ser Val Gln Leu Ala Asp His Tyr Gln Gln450 455 460Asn Thr Pro Ile Gly Asp Gly Pro Val Leu Leu Pro Asp Asn His Tyr465 470 475 480Leu Ser Thr Gln Ser Ala Leu Ser Lys Asp Pro Asn Glu Lys Arg Asp485 490 495His Met Val Leu Leu Glu Phe Val Thr Ala Ala Gly Ile Thr His Gly500 505 510Met Asp Glu Leu Tyr Lys515<210>161<211>1461<212>DNA<213>Artificial Sequence<220>
<223>Apo17<400>161atggatgaac ccccccagag cccctgggat cgagtgaagg acctggccac tgtgtacgtg 60gatgtgctca aagacagcgg cagagactat gtgtcccagt ttgaaggctc cgccttggga120aaacagctaa acctaaagct ccttgacaac tgggacagcg tgacctccac cttcagcaag180ctgcgcgaac agctcggccc tgtgacccag gagttctggg ataacctgga aaaggagaca240gagggcctga ggcaggagat gagcaaggat ctggaggagg tgaaggccaa ggtgcagccc300tacctggacg acttccagaa gaagtggcag gaggagatgg agctctaccg ccagaaggtg360gagccgctgc gcgcagagct ccaagagggc gcgcgccaga agctgcacga gctgcaagag420aagctgagcc cactgggcga ggagatgcgc gaccgcgcgc gcgcccatgt ggacgcgctg480cgcacgcatc tggcccccta cagcgacgag ctgcgccagc gcttggccgc gcgccttgag540gctctcaagg agaacggcgg cgccagactg gccgagtacc acgccaaggc caccgagcat600ctgagcacgc tcagcgagaa ggccaagccc gcgctcgagg acctccgcca aggcctgctg660
cccgtgctgg agagcttcaa ggtcagcttc ctgagcgctc tcgaggagta cactaagaag 720ctcaacaccc aggggatccc cttggctagt aaaggagaag aacttttcac tggagttgtc 780ccaattcttg ttgaattaga tggtgatgtt aatgggcaca aattttctgt cagtggagag 840ggtgaaggtg atgctacata cggaaagctt acccttaaat ttatttgcac tactggaaaa 900ctacctgttc cttggccaac acttgtcact actttctctt atggtgttca atgcttttca 960agatacccag atcatatgaa gcggcacgac ttcttcaaga gcgccatgcc tgagggatac1020gtgcaggaga ggaccatctc tttcaaggac gacgggaact acaagacacg tgctgaagtc1080aagtttgagg gagacaccct cgtcaacagg atcgagctta agggaatcga tttcaaggag1140gacggaaaca tcctcggcca caagttggaa tacaactaca actcccacaa cgtatacatc1200acggcagaca aacaaaagaa tggaatcaaa gctaacttca aaattagaca caacattgaa1260gatggaagcg ttcaactagc agaccattat caacaaaata ctccaattgg cgatggccct1320gtccttttac cagacaacca ttacctgtcc acacaatctg ccctttcgaa agatcccaac1380gaaaagagag accacatggt ccttcttgag tttgtaacag ctgctgggat tacacatggc1440atggatgaac tatacaaata a 1461<210>162<211>486<212>PRT<213>Artificial Sequence<220>
<223>Apo17<400>162Met Asp Glu Pro Pro Gln Ser Pro Trp Asp Arg Val Lys Asp Leu Ala1 5 10 15Thr Val Tyr Val Asp Val Leu Lys Asp Ser Gly Arg Asp Tyr Val Ser20 25 30Gln Phe Glu Gly Ser Ala Leu Gly Lys Gln Leu Asn Leu Lys Leu Leu35 40 45Asp Asn Trp Asp Ser Val Thr Ser Thr Phe Ser Lys Leu Arg Glu Gln50 55 60Leu Gly Pro Val Thr Gln Glu Phe Trp Asp Asn Leu Glu Lys Glu Thr65 70 75 80
Glu Gly Leu Arg Gln Glu Met Ser Lys Asp Leu Glu Glu Val Lys Ala85 90 95Lys Val Gln Pro Tyr Leu Asp Asp Phe Gln Lys Lys Trp Gln Glu Glu100 105 110Met Glu Leu Tyr Arg Gln Lys Val Glu Pro Leu Arg Ala Glu Leu Gln115 120 125Glu Gly Ala Arg Gln Lys Leu His Glu Leu Gln Glu Lys Leu Ser Pro130 135 140Leu Gly Glu Glu Met Arg Asp Arg Ala Arg Ala His Val Asp Ala Leu145 150 155 160Arg Thr His Leu Ala Pro Tyr Ser Asp Glu Leu Arg Gln Arg Leu Ala165 170 175Ala Arg Leu Glu Ala Leu Lys Glu Asn Gly Gly Ala Arg Leu Ala Glu180 185 190Tyr His Ala Lys Ala Thr Glu His Leu Ser Thr Leu Ser Glu Lys Ala195 200 205Lys Pro Ala Leu Glu Asp Leu Arg Gln Gly Leu Leu Pro Val Lau Glu210 215 220Ser Phe Lys Val Ser Phe Leu Ser Ala Leu Glu Glu Tyr Thr Lys Lys225 230 235 240Leu Asn Thr Gln Gly Ile Pro Leu Ala Ser Lys Gly Glu Glu Leu Phe245 250 255Thr Gly Val Val Pro Ile Leu Val Glu Leu Asp Gly Asp Val Asn Gly260 265 270His Lys Phe Ser Val Ser Gly Glu Gly Glu Gly Asp Ala Thr Tyr Gly275 280 285Lys Leu Thr Leu Lys Phe Ile Cys Thr Thr Gly Lys Leu Pro Val Pro290 295 300Trp Pro Thr Leu Val Thr Thr Phe Ser Tyr Gly Val Gln Cys Phe Ser305 310 315 320
Arg Tyr Pro Asp His Met Lys Arg His Asp Phe Phe Lys Ser Ala Met325 330 335Pro Glu Gly Tyr Val Gln Glu Arg Thr Ile Ser Phe Lys Asp Asp Gly340 345 350Asn Tyr Lys Thr Arg Ala Glu Val Lys Phe Glu Gly Asp Thr Leu Val355 360 365Asn Arg Ile Glu Leu Lys Gly Ile Asp Phe Lys Glu Asp Gly Asn Ile370 375 380Leu Gly His Lys Leu Glu Tyr Asn Tyr Asn Ser His Asn Val Tyr Ile385 390 395 400Thr Ala Asp Lys Gln Lys Asn Gly Ile Lys Ala Asn Phe Lys Ile Arg405 410 415His Asn Ile Glu Asp Gly Ser Val Gln Leu Ala Asp His Tyr Gln Gln420 425 430Asn Thr Pro Ile Gly Asp Gly Pro Val Leu Leu Pro Asp Asn His Tyr435 440 445Leu Ser Thr Gln Ser Ala Leu Ser Lys Asp Pro Asn Glu Lys Arg Asp450 455 460His Met Val Leu Leu Glu Phe Val Thr Ala Ala Gly Ile Thr His Gly465 470 475 480Met Asp Glu Leu Tyr Lys485<210>163<211>2970<212>DNA<213>Artificial Sequence<220>
<223>Apo18<400>163aattcgaatc caaaaattac ggatatgaat ataggcatat ccgtatccga attatccgtt 60tgacagctag caacgattgt acaattgctt ctttaaaaaa ggaagaaaga aagaaagaaa120
agaatcaaca tcagcgttaa caaacggccc cgttacggcc caaacggtca tatagagtaa 180cggcgttaag cgttgaaaga ctcctatcga aatacgtaac cgcaaacgtg tcatagtcag 240atcccctctt ccttcaccgc ctcaaacaca aaaataatct tctacagcct atatatacaa 300cccccccttc tatctctcct ttctcacaat tcatcatctt tctttctcta cccccaattt 360taagaaatcc tctcttctcc tcttcatttt caaggtaaat ctctctctct ctctctctct 420ctgttattcc ttgttttaat taggtatgta ttattgctag tttgttaatc tgcttatctt 480atgtatgcct tatgtgaata tctttatctt gttcatctca tccgtttaga agctataaat 540ttgttgattt gactgtgtat ctacacgtgg ttatgtttat atctaatcag atatgaattt 600cttcatattg ttgcgtttgt gtgtaccaat ccgaaatcgt tgattttttt catttaatcg 660tgtagctaat tgtacgtata catatggatc tacgtatcaa ttgttcatct gtttgtgttt 720gtatgtatac agatctgaaa acatcacttc tctcatctga ttgtgttgtt acatacatag 780atatagatct gttatatcat ttttttatta attgtgtata tatatatgtg catagatctg 840gattacatga ttgtgattat ttacatgatt ttgttattta cgtatgtata tatgtagatc 900tggacttttt ggagttgttg acttgattgt atttgtgtgt gtatatgtgt gttctgatct 960tgatatgtta tgtatgtgca gccccatggg gcggcatttc tggcagcaag atgaaccccc1020ccagagcccc tgggatcgag tgaaggacct ggccactgtg tacgtggatg tgctcaaaga1080cagcggcaga gactatgtgt cccagtttga aggctccgcc ttgggaaaac agctaaacct1140aaagctcctt gacaactggg acagcgtgac ctccaccttc agcaagctgc gcgaacagct1200cggccctgtg acccaggagt tctgggataa cctggaaaag gagacagagg gcctgaggca1260ggagatgagc aaggatctgg aggaggtgaa ggccaaggtg cagccctacc tggacgactt1320ccagaagaag tggcaggagg agatggagct ctaccgccag aaggtggagc cgctgcgcgc1380agagctccaa gagggcgcgc gccagaagct gcacgagctg caagagaagc tgagcccact1440gggcgaggag atgcgcgacc gcgcgcgcgc ccatgtggac gcgctgcgca cgcatctggc1500cccctacagc gacgagctgc gccagcgctt ggccgcgcgc cttgaggctc tcaaggagaa1560cggcggcgcc agactggccg agtaccacgc caaggccacc gagcatctga gcacgctcag1620cgagaaggcc aagcccgcgc tcgaggacct ccgccaaggc ctgctgcccg tgctggagag1680cttcaaggtc agcttcctga gcgctctcga ggagtacact aagaagctca acacccaggg1740gatccccttg gctagtaaag gagaagaact tttcactgga gttgtcccaa ttcttgttga1800attagatggt gatgttaatg ggcacaaatt ttctgtcagt ggagagggtg aaggtgatgc1860tacatacgga aagcttaccc ttaaatttat ttgcactact ggaaaactac ctgttccttg1920
gccaacactt gtcactactt tctcttatgg tgttcaatgc ttttcaagat acccagatca1980tatgaagcgg cacgacttct tcaagagcgc catgcctgag ggatacgtgc aggagaggac2040catctctttc aaggacgacg ggaactacaa gacacgtgct gaagtcaagt ttgagggaga2100caccctcgtc aacaggatcg agcttaaggg aatcgatttc aaggaggacg gaaacatcct2160cggccacaag ttggaataca actacaactc ccacaacgta tacatcacgg cagacaaaca2220aaagaatgga atcaaagcta acttcaaaat tagacacaac attgaagatg gaagcgttca2280actagcagac cattatcaac aaaatactcc aattggcgat ggccctgtcc ttttaccaga2340caaccattac ctgtccacac aatctgccct ttcgaaagat cccaacgaaa agagagacca2400catggtcctt cttgagtttg taacagctgc tgggattaca catggcatgg atgaactata2460caaataagtc atgactgcag aatgagttcc aagatggttt gtgacgaagt tagttggttg2520tttttatgga actttgttta agcttgtaat gtggaaagaa cgtgtggctt tgtggttttt2580aaatgttggt gaataaagat gtttcctttg gattaactag tatttttcct attggtttca2640tggttttagc acacaacatt ttaaatatgc tgttagatga tatgctgcct gctttattat2700ttacttaccc ctcaccttca gtttcaaagt tgttgcaatg actctgtgta gtttaagatc2760gagtgaaagt agattttgtc tatatttatt aggggtattt gatatgctaa tggtaaacat2820ggtttatgac agcgtacttt tttggttatg gtgttgacgt ttccttttaa acattatagt2880agcgtccttg gtctgtgttc attggttgaa caaaggcaca ctcacttgga gatgccgtct2940ccactgatat ttgaacaaag aattcggtac 2970<210>164<211>493<212>PRT<213>Artificial Sequence<220>
<223>Apo18<400>164Met Gly Arg His Phe Trp Gln Gln Asp Glu Pro Pro Gln Ser Pro Trp1 5 10 15Asp Arg Val Lys Asp Leu Ala Thr Val Tyr Val Asp Val Leu Lys Asp20 25 30Ser Gly Arg Asp Tyr Val Ser Gln Phe Glu Gly Ser Ala Leu Gly Lys35 40 45
Gln Leu Asn Leu Lys Leu Leu Asp Asn Trp Asp Ser Val Thr Ser Thr50 55 60Phe Ser Lys Leu Arg Glu Gln Leu Gly Pro Val Thr Gln Glu Phe Trp65 70 75 80Asp Asn Leu Glu Lys Glu Thr Glu Gly Leu Arg Gln Glu Met Ser Lys85 90 95Asp Leu Glu Glu Val Lys Ala Lys Val Gln Pro Tyr Leu Asp Asp Phe100 105 110Gln Lys Lys Trp Gln Glu Glu Met Glu Leu Tyr Arg Gln Lys Val Glu115 120 125Pro Leu Arg Ala Glu Leu Gln Glu Gly Ala Arg Gln Lys Leu His Glu130 135 140Leu Gln Glu Lys Leu Ser Pro Leu Gly Glu Glu Met Arg Asp Arg Ala145 150 155 160Arg Ala His Val Asp Ala Leu Arg Thr His Leu Ala Pro Tyr Ser Asp165 170 175Glu Leu Arg Gln Arg Leu Ala Ala Arg Leu Glu Ala Leu Lys Glu Asn180 185 190Gly Gly Ala Arg Leu Ala Glu Tyr His Ala Lys Ala Thr Glu His Leu195 200 205Ser Thr Leu Ser Glu Lys Ala Lys Pro Ala Leu Glu Asp Leu Arg Gln210 215 220Gly Leu Leu Pro Val Leu Glu Ser Phe Lys Val Ser Phe Leu Ser Ala225 230 235 240Leu Glu Glu Tyr Thr Lys Lys Leu Asn Thr Gln Gly Ile Pro Leu Ala245 250 255Ser Lys Gly Glu Glu Leu Phe Thr Gly Val Val Pro Ile Leu Val Glu260 265 270Leu Asp Gly Asp Val Asn Gly His Lys Phe Ser Val Ser Gly Glu Gly275 280 285
Glu Gly Asp Ala Thr Tyr Gly Lys Leu Thr Leu Lys Phe Ile Cys Thr290 295 300Thr Gly Lys Leu Pro Val Pro Trp Pro Thr Leu Val Thr Thr Phe Ser305 310 315 320Tyr Gly Val Gln Cys Phe Ser Arg Tyr Pro Asp His Met Lys Arg His325 330 335Asp Phe Phe Lys Ser Ala Met Pro Glu Gly Tyr Val Gln Glu Arg Thr340 345 350Ile Ser Phe Lys Asp Asp Gly Asn Tyr Lys Thr Arg Ala Glu Val Lys355 360 365Phe Glu Gly Asp Thr Leu Val Asn Arg Ile Glu Leu Lys Gly Ile Asp370 375 380Phe Lys Glu Asp Gly Asn Ile Leu Gly His Lys Leu Glu Tyr Asn Tyr385 390 395 400Asn Ser His Asn Val Tyr Ile Thr Ala Asp Lys Gln Lys Asn Gly Ile405 410 415Lys Ala Asn Phe Lys Ile Arg His Asn Ile Glu Asp Gly Ser Val Gln420 425 430Leu Ala Asp His Tyr Gln Gln Asn Thr Pro Ile Gly Asp Gly Pro Val435 440 445Leu Leu Pro Asp Asn His Tyr Leu Ser Thr Gln Ser Ala Leu Ser Lys450 455 460Asp Pro Asn Glu Lys Arg Asp His Met Val Leu Leu Glu Phe Val Thr465 470 475 480Ala Ala Gly Ile Thr His Gly Met Asp Glu Leu Tyr Lys485 490<210>165<211>3043<212>DNA<213>Artificial Sequence
<220>
<223>Apo19<400>165aattcgaatc caaaaattac ggatatgaat ataggcatat ccgtatccga attatccgtt 60tgacagctag caacgattgt acaattgctt ctttaaaaaa ggaagaaaga aagaaagaaa 120agaatcaaca tcagcgttaa caaacggccc cgttacggcc caaacggtca tatagagtaa 180cggcgttaag cgttgaaaga ctcctatcga aatacgtaac cgcaaacgtg tcatagtcag 240atcccctctt ccttcaccgc ctcaaacaca aaaataatct tctacagcct atatatacaa 300cccccccttc tatctctcct ttctcacaat tcatcatctt tctttctcta cccccaattt 360taagaaatcc tctcttctcc tcttcatttt caaggtaaat ctctctctct ctctctctct 420ctgttattcc ttgttttaat taggtatgta ttattgctag tttgttaatc tgcttatctt 480atgtatgcct tatgtgaata tctttatctt gttcatctca tccgtttaga agctataaat 540ttgttgattt gactgtgtat ctacacgtgg ttatgtttat atctaatcag atatgaattt 600cttcatattg ttgcgtttgt gtgtaccaat ccgaaatcgt tgattttttt catttaatcg 660tgtagctaat tgtacgtata catatggatc tacgtatcaa ttgttcatct gtttgtgttt 720gtatgtatac agatctgaaa acatcacttc tctcatctga ttgtgttgtt acatacatag 780atatagatct gttatatcat ttttttatta attgtgtata tatatatgtg catagatctg 840gattacatga ttgtgattat ttacatgatt ttgttattta cgtatgtata tatgtagatc 900tggacttttt ggagttgttg acttgattgt atttgtgtgt gtatatgtgt gttctgatct 960tgatatgtta tgtatgtgca gccaaggcta cgggcgatcc acccatgaac ttccttaagt1020ctttcccttt ctacgctttc ctttgtttcg gtcaatactt cgttgctgtt acgcatgcca1080tggatgaacc cccccagagc ccctgggatc gagtgaagga cctggccact gtgtacgtgg1140atgtgctcaa agacagcggc agagactatg tgtcccagtt tgaaggctcc gccttgggaa1200aacagctaaa cctaaagctc cttgacaact gggacagcgt gacctccacc ttcagcaagc1260tgcgcgaaca gctcggccct gtgacccagg agttctggga taacctggaa aaggagacag1320agggcctgag gcaggagatg agcaaggatc tggaggaggt gaaggccaag gtgcagccct1380acctggacga cttccagaag aagtggcagg aggagatgga gctctaccgc cagaaggtgg1440agccgctgcg cgcagagctc caagagggcg cgcgccagaa gctgcacgag ctgcaagaga1500agctgagccc actgggcgag gagatgcgcg accgcgcgcg cgcccatgtg gacgcgctgc1560gcacgcatct ggccccctac agcgacgagc tgcgccagcg cttggccgcg cgccttgagg1620ctctcaagga gaacggcggc gccagactgg ccgagtacca cgccaaggcc accgagcatc1680
tgagcacgct cagcgagaag gccaagcccg cgctcgagga cctccgccaa ggcctgctgc1740ccgtgctgga gagcttcaag gtcagcttcc tgagcgctct cgaggagtac actaagaagc1800tcaacaccca ggggatcccc ttggctagta aaggagaaga acttttcact ggagttgtcc1860caattcttgt tgaattagat ggtgatgtta atgggcacaa attttctgtc agtggagagg1920gtgaaggtga tgctacatac ggaaagctta cccttaaatt tatttgcact actggaaaac1980tacctgttcc ttggccaaca cttgtcacta ctttctctta tggtgttcaa tgcttttcaa2040gatacccaga tcatatgaag cggcacgact tcttcaagag cgccatgcct gagggatacg2100tgcaggagag gaccatctct ttcaaggacg acgggaacta caagacacgt gctgaagtca2160agtttgaggg agacaccctc gtcaacagga tcgagcttaa gggaatcgat ttcaaggagg2220acggaaacat cctcggccac aagttggaat acaactacaa ctcccacaac gtatacatca2280cggcagacaa acaaaagaat ggaatcaaag ctaacttcaa aattagacac aacattgaag2340atggaagcgt tcaactagca gaccattatc aacaaaatac tccaattggc gatggccctg2400tccttttacc agacaaccat tacctgtcca cacaatctgc cctttcgaaa gatcccaacg2460aaaagagaga ccacatggtc cttcttgagt ttgtaacagc tgctgggatt acacatggca2520tggatgaact atacaaataa gtcatgactg caggtcgacc gaatgagttc caagatggtt2580tgtgacgaag ttagttggtt gtttttatgg aactttgttt aagctagctt gtaatgtgga2640aagaacgtgt ggctttgtgg tttttaaatg ttggtgaata aagatgtttc ctttggatta2700actagtattt ttcctattgg tttcatggtt ttagcacaca acattttaaa tatgctgtta2760gatgatatgc tgcctgcttt attatttact tacccctcac cttcagtttc aaagttgttg2820caatgactct gtgtagttta agatcgagtg aaagtagatt ttgtctatat ttattagggg2880tatttgatat gctaatggta aacatggttt atgacagcgt acttttttgg ttatggtgtt2940gacgtttcct tttaaacatt atagtagcgt ccttggtctg tgttcattgg ttgaacaaag3000gcacactcac ttggagatgc cgtctccact gatatttgaa caa 3043<210>166<211>511<212>PRT<213>Artificial Sequence<220>
<223>Apo19<400>166Met Asn Phe Leu Lys Ser Phe Pro Phe Tyr Ala Phe Leu Cys Phe Gly
1 5 10 15Gln Tyr Phe Val Ala Val Thr His Ala Met Asp Glu Pro Pro Gln Ser20 25 30Pro Trp Asp Arg Val Lys Asp Leu Ala Thr Val Tyr Val Asp Val Leu35 40 45Lys Asp Ser Gly Arg Asp Tyr Val Ser Gln Phe Glu Gly Ser Ala Leu50 55 60Gly Lys Gln Leu Asn Leu Lys Leu Leu Asp Asn Trp Asp Ser Val Thr65 70 75 80Ser Thr Phe Ser Lys Leu Arg Glu Gln Leu Gly Pro Val Thr Gln Glu85 90 95Phe Trp Asp Asn Leu Glu Lys Glu Thr Glu Gly Leu Arg Gln Glu Met100 105 110Ser Lys Asp Leu Glu Glu Val Lys Ala Lys Val Gln Pro Tyr Leu Asp115 120 125Asp Phe Gln Lys Lys Trp Gln Glu Glu Met Glu Leu Tyr Arg Gln Lys130 135 140Val Glu Pro Leu Arg Ala Glu Leu Gln Glu Gly Ala Arg Gln Lys Leu145 150 155 160His Glu Leu Gln Glu Lys Leu Ser Pro Leu Gly Glu Glu Met Arg Asp165 170 175Arg Ala Arg Ala His Val Asp Ala Leu Arg Thr His Leu Ala Pro Tyr180 185 190Ser Asp Glu Leu Arg Gln Arg Leu Ala Ala Arg Leu Glu Ala Leu Lys195 200 205Glu Asn Gly Gly Ala Arg Leu Ala Glu Tyr His Ala Lys Ala Thr Glu210 215 220His Leu Ser Thr Leu Ser Glu Lys Ala Lys Pro Ala Leu Glu Asp Leu225 230 235 240
Arg Gln Gly Leu Leu Pro Val Leu Glu Ser Phe Lys Val Ser Phe Leu245 250 255Ser Ala Leu Glu Glu Tyr Thr Lys Lys Leu Asn Thr Gln Gly Ile Pro260 265 270Leu Ala Ser Lys Gly Glu Glu Leu Phe Thr Gly Val Val Pro Ile Leu275 280 285Val Glu Leu Asp Gly Asp Val Asn Gly His Lys Phe Ser Val Ser Gly290 295 300Glu Gly Glu Gly Asp Ala Thr Tyr Gly Lys Leu Thr Leu Lys Phe Ile305 310 315 320Cys Thr Thr Gly Lys Leu Pro Val Pro Trp Pro Thr Leu Val Thr Thr325 330 335Phe Ser Tyr Gly Val Gln Cys Phe Ser Arg Tyr Pro Asp His Met Lys340 345 350Arg His Asp Phe Phe Lys Ser Ala Met Pro Glu Gly Tyr Val Gln Glu355 360 365Arg Thr Ile Ser Phe Lys Asp Asp Gly Asn Tyr Lys Thr Arg Ala Glu370 375 380Val Lys Phe Glu Gly Asp Thr Leu Val Asn Arg Ile Glu Leu Lys Gly385 390 395 400Ile Asp Phe Lys Glu Asp Gly Asn Ile Leu Gly His Lys Leu Glu Tyr405 410 415Asn Tyr Asn Ser His Asn Val Tyr Ile Thr Ala Asp Lys Gln Lys Asn420 425 430Gly Ile Lys Ala Asn Phe Lys Ile Arg His Asn Ile Glu Asp Gly Ser435 440 445Val Gln Leu Ala Asp His Tyr Gln Gln Asn Thr Pro Ile Gly Asp Gly450 455 460Pro Val Leu Leu Pro Asp Asn His Tyr Leu Ser Thr Gln Ser Ala Leu465 470 475 480
Ser Lys Asp Pro Asn Glu Lys Arg Asp His Met Val Leu Leu Glu Phe485 490 495Val Thr Ala Ala Gly Ile Thr His Gly Met Asp Glu Leu Tyr Lys500 505 510<210>167<211>31<212>DNA<213>Artificial Sequence<220>
<223>forward primer 1177<400>167gcagcattca tgaacttcct taagtctttc c 31<210>168<211>35<212>DNA<213>Artificial Sequence<220>
<223>reverse primer 1178<400>168ggtggtggat cccctgggtg ttgagcttct tagtg 35<210>169<211>3059<212>DNA<213>Artificial Sequence<220>
<223>Apo20<400>169gaatccaaaa attacggata tgaatatagg catatccgta tccgaattat ccgtttgaca 60gctagcaacg attgtacaat tgcttcttta aaaaaggaag aaagaaagaa agaaaagaat120caacatcagc gttaacaaac ggccccgtta cggcccaaac ggtcatatag agtaacggcg180ttaagcgttg aaagactcct atcgaaatac gtaaccgcaa acgtgtcata gtcagatccc240ctcttccttc accgcctcaa acacaaaaat aatcttctac agcctatata tacaaccccc300ccttctatct ctcctttctc acaattcatc atctttcttt ctctaccccc aattttaaga360aatcctctct tctcctcttc attttcaagg taaatctctc tctctctctc tctctctgtt420attccttgtt ttaattaggt atgtattatt gctagtttgt taatctgctt atcttatgta480tgccttatgt gaatatcttt atcttgttca tctcatccgt ttagaagcta taaatttgtt540
gatttgactg tgtatctaca cgtggttatg tttatatcta atcagatatg aatttcttca 600tattgttgcg tttgtgtgta ccaatccgaa atcgttgatt tttttcattt aatcgtgtag 660ctaattgtac gtatacatat ggatctacgt atcaattgtt catctgtttg tgtttgtatg 720tatacagatc tgaaaacatc acttctctca tctgattgtg ttgttacata catagatata 780gatctgttat atcatttttt tattaattgt gtatatatat atgtgcatag atctggatta 840catgattgtg attatttaca tgattttgtt atttacgtat gtatatatgt agatctggac 900tttttggagt tgttgacttg attgtatttg tgtgtgtata tgtgtgttct gatcttgata 960tgttatgtat gtgcagccaa ggctacgggc gatccaccca tgaacttcct taagtctttc1020cctttctacg ctttcctttg tttcggtcaa tacttcgttg ctgttacgca tgccatgggg1080cggcatttct ggcagcaaga tgaacccccc cagagcccct gggatcgagt gaaggacctg1140gccactgtgt acgtggatgt gctcaaagac agcggcagag actatgtgtc ccagtttgaa1200ggctccgcct tgggaaaaca gctaaaccta aagctccttg acaactggga cagcgtgacc1260tccaccttca gcaagctgcg cgaacagctc ggccctgtga cccaggagtt ctgggataac1320ctggaaaagg agacagaggg cctgaggcag gagatgagca aggatctgga ggaggtgaag1380gccaaggtgc agccctacct ggacgacttc cagaagaagt ggcaggagga gatggagctc1440taccgccaga aggtggagcc gctgcgcgca gagctccaag agggcgcgcg ccagaagctg1500cacgagctgc aagagaagct gagcccactg ggcgaggaga tgcgcgaccg cgcgcgcgcc1560catgtggacg cgctgcgcac gcatctggcc ccctacagcg acgagctgcg ccagcgcttg1620gccgcgcgcc ttgaggctct caaggagaac ggcggcgcca gactggccga gtaccacgcc1680aaggccaccg agcatctgag cacgctcagc gagaaggcca agcccgcgct cgaggacctc1740cgccaaggcc tgctgcccgt gctggagagc ttcaaggtca gcttcctgag cgctctcgag1800gagtacacta agaagctcaa cacccagggg atccccttgg ctagtaaagg agaagaactt1860ttcactggag ttgtcccaat tcttgttgaa ttagatggtg atgttaatgg gcacaaattt1920tctgtcagtg gagagggtga aggtgatgct acatacggaa agcttaccct taaatttatt1980tgcactactg gaaaactacc tgttccttgg ccaacacttg tcactacttt ctcttatggt2040gttcaatgct tttcaagata cccagatcat atgaagcggc acgacttctt caagagcgcc2100atgcctgagg gatacgtgca ggagaggacc atctctttca aggacgacgg gaactacaag2160acacgtgctg aagtcaagtt tgagggagac accctcgtca acaggatcga gcttaaggga2220atcgatttca aggaggacgg aaacatcctc ggccacaagt tggaatacaa ctacaactcc2280
cacaacgtat acatcacggc agacaaacaa aagaatggaa tcaaagctaa cttcaaaatt2340agacacaaca ttgaagatgg aagcgttcaa ctagcagacc attatcaaca aaatactcca2400attggcgatg gccctgtcct tttaccagac aaccattacc tgtccacaca atctgccctt2460tcgaaagatc ccaacgaaaa gagagaccac atggtccttc ttgagtttgt aacagctgct2520gggattacac atggcatgga tgaactatac aaataagtca tgactgcagg tcgaccgaat2580gagttccaag atggtttgtg acgaagttag ttggttgttt ttatggaact ttgtttaagc2640tagcttgtaa tgtggaaaga acgtgtggct ttgtggtttt taaatgttgg tgaataaaga2700tgtttccttt ggattaacta gtatttttcc tattggtttc atggttttag cacacaacat2760tttaaatatg ctgttagatg atatgctgcc tgctttatta tttacttacc cctcaccttc2820agtttcaaag ttgttgcaat gactctgtgt agtttaagat cgagtgaaag tagattttgt2880ctatatttat taggggtatt tgatatgcta atggtaaaca tggtttatga cagcgtactt2940ttttggttat ggtgttgacg tttcctttta aacattatag tagcgtcctt ggtctgtgtt3000cattggttga acaaaggcac actcacttgg agatgccgtc tccactgata tttgaacaa 3059<210>170<211>518<212>PRT<213>Artificial Sequence<220>
<223>Apo20<400>170Met Asn Phe Leu Lys Ser Phe Pro Phe Tyr Ala Phe Leu Cys Phe Gly1 5 10 15Gln Tyr Phe Val Ala Val Thr His Ala Met Gly Arg His Phe Trp Gln20 25 30Gln Asp Glu Pro Pro Gln Ser Pro Trp Asp Arg Val Lys Asp Leu Ala35 40 45Thr Val Tyr Val Asp Val Leu Lys Asp Ser Gly Arg Asp Tyr Val Ser50 55 60Gln Phe Glu Gly Ser Ala Leu Gly Lys Gln Leu Asn Leu Lys Leu Leu65 70 75 80Asp Asn Trp Asp Ser Val Thr Ser Thr Phe Ser Lys Leu Arg Glu Gln85 90 95
Leu Gly Pro Val Thr Gln Glu Phe Trp Asp Asn Leu Glu Lys Glu Thr100 105 110Glu Gly Leu Arg Gln Glu Met Ser Lys Asp Leu Glu Glu Val Lys Ala115 120 125Lys Val Gln Pro Tyr Leu Asp Asp Phe Gln Lys Lys Trp Gln Glu Glu130 135 140Met Glu Leu Tyr Arg Gln Lys Val Glu Pro Leu Arg Ala Glu Leu Gln145 150 155 160Glu Gly Ala Arg Gln Lys Leu His Glu Leu Gln Glu Lys Leu Ser Pro165 170 175Leu Gly Glu Glu Met Arg Asp Arg Ala Arg Ala His Val Asp Ala Leu180 185 190Arg Thr His Leu Ala Pro Tyr Ser Asp Glu Leu Arg Gln Arg Leu Ala195 200 205Ala Arg Leu Glu Ala Leu Lys Glu Asn Gly Gly Ala Arg Leu Ala Glu210 215 220Tyr His Ala Lys Ala Thr Glu His Leu Ser Thr Leu Ser Glu Lys Ala225 230 235 240Lys Pro Ala Leu Glu Asp Leu Arg Gln Gly Leu Leu Pro Val Leu Glu245 250 255Ser Phe Lys Val Ser Phe Leu Ser Ala Leu Glu Glu Tyr Thr Lys Lys260 265 270Leu Asn Thr Gln Gly Ile Pro Leu Ala Ser Lys Gly Glu Glu Leu Phe275 280 285Thr Gly Val Val Pro Ile Leu Val Glu Leu Asp Gly Asp Val Asn Gly290 295 300His Lys Phe Ser Val Ser Gly Glu Gly Glu Gly Asp Ala Thr Tyr Gly305 310 315 320Lys Leu Thr Leu Lys Phe Ile Cys Thr Thr Gly Lys Leu Pro Val Pro
325 330 335Trp Pro Thr Leu Val Thr Thr Phe Ser Tyr Gly Val Gln Cys Phe Ser340 345 350Arg Tyr Pro Asp His Met Lys Arg His Asp Phe Phe Lys Ser Ala Met355 360 365Pro Glu Gly Tyr Val Gln Glu Arg Thr Ile Ser Phe Lys Asp Asp Gly370 375 380Asn Tyr Lys Thr Arg Ala Glu Val Lys Phe Glu Gly Asp Thr Leu Val385 390 395 400Asn Arg Ile Glu Leu Lys Gly Ile Asp Phe Lys Glu Asp Gly Asn Ile405 410 415Leu Gly His Lys Leu Glu Tyr Asn Tyr Asn Ser His Asn Val Tyr Ile420 425 430Thr Ala Asp Lys Gln Lys Asn Gly Ile Lys Ala Asn Phe Lys Ile Arg435 440 445His Asn Ile Glu Asp Gly Ser Val Gln Leu Ala Asp His Tyr Gln Gln450 455 460Asn Thr Pro Ile Gly Asp Gly Pro Val Leu Leu Pro Asp Asn His Tyr465 470 475 480Leu Ser Thr Gln Ser Ala Leu Ser Lys Asp Pro Asn Glu Lys Arg Asp485 490 495His Met Val Leu Leu Glu Phe Val Thr Ala Ala Gly Ile Thr His Gly500 505 510Met Asp Glu Leu Tyr Lys515<210>171<211>3510<212>DNA<213>Artificial Sequence<220>
<223>Apo21
<400>171gaattcattg tactcccagt atcattatag tgaaagtttt ggctctctcg ccggtggttt 60tttacctcta tttaaagggg ttttccacct aaaaattctg gtatcattct cactttactt 120gttactttaa tttctcataa tctttggttg aaattatcac gcttccgcac acgatatccc 180tacaaattta ttatttgtta aacattttca aaccgcataa aattttatga agtcccgtct 240atctttaatg tagtctaaca ttttcatatt gaaatatata atttacttaa ttttagcgtt 300ggtagaaagc ataaagattt attcttattc ttcttcatat aaatgtttaa tatacaatat 360aaacaaattc tttaccttaa gaaggatttc ccattttata ttttaaaaat atatttatca 420aatatttttc aaccacgtaa atctcataat aataagttgt ttcaaaagta ataaaattta 480actccataat ttttttattc gactgatctt aaagcaacac ccagtgacac aactagccat 540ttttttcttt gaataaaaaa atccaattat cattgtattt tttttataca atgaaaattt 600caccaaacaa tcatttgtgg tatttctgaa gcaagtcatg ttatgcaaaa ttctataatt 660cccatttgac actacggaag taactgaaga tctgctttta catgcgagac acatcttcta 720aagtaatttt aataatagtt actatattca agatttcata tatcaaatac tcaatattac 780ttctaaaaaa ttaattagat ataattaaaa tattactttt ttaattttaa gtttaattgt 840tgaatttgtg actattgatt tattattcta ctatgtttaa attgttttat agatagttta 900aagtaaatat aagtaatgta gtagagtgtt agagtgttac cctaaaccat aaactataac 960atttatggtg gactaatttt catatatttc ttattgcttt taccttttct tggtatgtaa1020gtccgtaact agaattacag tgggttgcca tgacactctg tggtcttttg gttcatgcat1080gggtcttgcg caagaaaaag acaaagaaca aagaaaaaag acaaaacaga gagacaaaac1140gcaatcacac aaccaactca aattagtcac tggctgatca agatcgccgc gtccatgtat1200gtctaaatgc catgcaaagc aacacgtgct taacatgcac tttaaatggc tcacccatct1260caacccacac acaaacacat tgcctttttc ttcatcatca ccacaaccac ctgtatatat1320tcattctctt ccgccacctc aatttcttca cttcaacaca cgtcaacctg catatgcgtg1380tcatcccatg cccaaatctc catgcatgtt ccaaccacct tctctcttat ataataccta1440taaatacctc taatatcact cacttctttc atcatccatc catccagagt actactactc1500tactactata ataccccaac ccaactcata ttcaatacta ctctaccatg gatgaacccc1560cccagagccc ctgggatcga gtgaaggacc tggccactgt gtacgtggat gtgctcaaag1620acagcggcag agactatgtg tcccagtttg aaggctccgc cttgggaaaa cagctaaacc1680taaagctcct tgacaactgg gacagcgtga cctccacctt cagcaagctg cgcgaacagc1740
tcggccctgt gacccaggag ttctgggata acctggaaaa ggagacagag ggcctgaggc1800aggagatgag caaggatctg gaggaggtga aggccaaggt gcagccctac ctggacgact1860tccagaagaa gtggcaggag gagatggagc tctaccgcca gaaggtggag ccgctgcgcg1920cagagctcca agagggcgcg cgccagaagc tgcacgagct gcaagagaag ctgagcccac1980tgggcgagga gatgcgcgac cgcgcgcgcg cccatgtgga cgcgctgcgc acgcatctgg2040ccccctacag cgacgagctg cgccagcgct tggccgcgcg ccttgaggct ctcaaggaga2100acggcggcgc cagactggcc gagtaccacg ccaaggccac cgagcatctg agcacgctca2160gcgagaaggc caagcccgcg ctcgaggacc tccgccaagg cctgctgccc gtgctggaga2220gcttcaaggt cagcttcctg agcgctctcg aggagtacac taagaagctc aacacccagt2280gaaagcttaa ataagtatga actaaaatgc atgtaggtgt aagagctcat ggagagcatg2340gaatattgta tccgaccatg taacagtata ataactgagc tccatctcac ttcttctatg2400aataaacaaa ggatgttatg atatattaac actctatcta tgcaccttat tgttctatga2460taaatttcct cttattatta taaatcatct gaatcgtgac ggcttatgga atgcttcaaa2520tagtacaaaa acaaatgtgt actataagac tttctaaaca attctaactt tagcattgtg2580aacgagacat aagtgttaag aagacataac aattataatg gaagaagttt gtctccattt2640atatattata tattacccac ttatgtatta tattaggatg ttaaggagac ataacaatta2700taaagagaga agtttgtatc catttatata ttatatacta cccatttata tattatactt2760atccacttat ttaatgtctt tataaggttt gatccatgat atttctaata ttttagttga2820tatgtatatg aaaaggtact atttgaactc tcttactctg tataaaggtt ggatcatcct2880taaagtgggt ctatttaatt ttattgcttc ttacagataa aaaaaaaatt atgagttggt2940ttgataaaat attgaaggat ttaaaataat aataaataat aaataacata taatatatgt3000atataaattt attataatat aacatttatc tataaaaaag taaatattgt cataaatcta3060tacaatcgtt tagccttgct ggaacgaatc tcaattattt aaacgagagt aaacatattt3120gactttttgg ttatttaaca aattattatt taacactata tgaaattttt tttttttatc3180agcaaagaaa taaaattaaa ttaagaagga caatggtgtg tcccaatcct tatacaacca3240acttccacaa gaaagtcaag tcagagacaa caaaaaaaca agcaaaggaa attttttaat3300ttgagttgtc ttgtttgctg cataatttat gcagtaaaac actacacata acccttttag3360cagtagagca atggttgacc gtgtgcttag cttcttttat tttatttttt tatcagcaaa3420gaataaataa aataaaatga gacacttcag ggatgtttca acccttatac aaaaccccaa3480aaacaagttt cctagcaccc taccaactaa 3510
<210>172<211>244<212>PRT<213>Artificial Sequence<220>
<223>Apo21<400>172Met Asp Glu Pro Pro Gln Ser Pro Trp Asp Arg Val Lys Asp Leu Ala1 5 10 15Thr Val Tyr Val Asp Val Leu Lys Asp Ser Gly Arg Asp Tyr Val Ser20 25 30Gln Phe Glu Gly Ser Ala Leu Gly Lys Gln Leu Asn Leu Lys Leu Leu35 40 45Asp Asn Trp Asp Ser Val Thr Ser Thr Phe Ser Lys Leu Arg Glu Gln50 55 60Leu Gly Pro Val Thr Gln Glu Phe Trp Asp Asn Leu Glu Lys Glu Thr65 70 75 80Glu Gly Leu Arg Gln Glu Met Ser Lys Asp Leu Glu Glu Val Lys Ala85 90 95Lys Val Gln Pro Tyr Leu Asp Asp Phe Gln Lys Lys Trp Gln Glu Glu100 105 110Met Glu Leu Tyr Arg Gln Lys Val Glu Pro Leu Arg Ala Glu Leu Gln115 120 125Glu Gly Ala Arg Gln Lys Leu His Glu Leu Gln Glu Lys Leu Ser Pro130 135 140Leu Gly Glu Glu Met Arg Asp Arg Ala Arg Ala His Val Asp Ala Leu145 150 155 160Arg Thr His Leu Ala Pro Tyr Ser Asp Glu Leu Arg Gln Arg Leu Ala165 170 175Ala Arg Leu Glu Ala Leu Lys Glu Asn Gly Gly Ala Arg Leu Ala Glu180 185 190
Tyr His Ala Lys Ala Thr Glu His Leu Ser Thr Leu Ser Glu Lys Ala195 200 205Lys Pro Ala Leu Glu Asp Leu Arg Gln Gly Leu Leu Pro Val Leu Glu210 215 220Ser Phe Lys Val Ser Phe Leu Ser Ala Leu Glu Glu Tyr Thr Lys Lys225 230 235 240Leu Asn Thr Gln<210>173<211>34<212>DNA<213>Artificial Sequence<220>
<223>forward primer 1203<400>173gcagcaccat ggatgaaccc ccccagagcc cctg 34<210>174<211>52<212>DNA<213>Artificial Sequence<220>
<223>forward primer 1206<400>174gtggtgaagc tttcactggg tgttgagctt cttagtgtac tcctccagag cg 52<210>175<211>3531<212>DNA<213>Artificial Sequence<220>
<223>Apo22<400>175gaattcattg tactcccagt atcattatag tgaaagtttt ggctctctcg ccggtggttt 60tttacctcta tttaaagggg ttttccacct aaaaattctg gtatcattct cactttactt120gttactttaa tttctcataa tctttggttg aaattatcac gcttccgcac acgatatccc180tacaaattta ttatttgtta aacattttca aaccgcataa aattttatga agtcccgtct240atctttaatg tagtctaaca ttttcatatt gaaatatata atttacttaa ttttagcgtt300
ggtagaaagc ataaagattt attcttattc ttcttcatat aaatgtttaa tatacaatat 360aaacaaattc tttaccttaa gaaggatttc ccattttata ttttaaaaat atatttatca 420aatatttttc aaccacgtaa atctcataat aataagttgt ttcaaaagta ataaaattta 480actccataat ttttttattc gactgatctt aaagcaacac ccagtgacac aactagccat 540ttttttcttt gaataaaaaa atccaattat cattgtattt tttttataca atgaaaattt 600caccaaacaa tcatttgtgg tatttctgaa gcaagtcatg ttatgcaaaa ttctataatt 660cccatttgac actacggaag taactgaaga tctgctttta catgcgagac acatcttcta 720aagtaatttt aataatagtt actatattca agatttcata tatcaaatac tcaatattac 780ttctaaaaaa ttaattagat ataattaaaa tattactttt ttaattttaa gtttaattgt 840tgaatttgtg actattgatt tattattcta ctatgtttaa attgttttat agatagttta 900aagtaaatat aagtaatgta gtagagtgtt agagtgttac cctaaaccat aaactataac 960atttatggtg gactaatttt catatatttc ttattgcttt taccttttct tggtatgtaa1020gtccgtaact agaattacag tgggttgcca tgacactctg tggtcttttg gttcatgcat1080gggtcttgcg caagaaaaag acaaagaaca aagaaaaaag acaaaacaga gagacaaaac1140gcaatcacac aaccaactca aattagtcac tggctgatca agatcgccgc gtccatgtat1200gtctaaatgc catgcaaagc aacacgtgct taacatgcac tttaaatggc tcacccatct1260caacccacac acaaacacat tgcctttttc ttcatcatca ccacaaccac ctgtatatat1320tcattctctt ccgccacctc aatttcttca cttcaacaca cgtcaacctg catatgcgtg1380tcatcccatg cccaaatctc catgcatgtt ccaaccacct tctctcttat ataataccta1440taaatacctc taatatcact cacttctttc atcatccatc catccagagt actactactc1500tactactata ataccccaac ccaactcata ttcaatacta ctctaccatg gggcggcatt1560tctggcagca agatgaaccc ccccagagcc cctgggatcg agtgaaggac ctggccactg1620tgtacgtgga tgtgctcaaa gacagcggca gagactatgt gtcccagttt gaaggctccg1680ccttgggaaa acagctaaac ctaaagctcc ttgacaactg ggacagcgtg acctccacct1740tcagcaagct gcgcgaacag ctcggccctg tgacccagga gttctgggat aacctggaaa1800aggagacaga gggcctgagg caggagatga gcaaggatct ggaggaggtg aaggccaagg1860tgcagcccta cctggacgac ttccagaaga agtggcagga ggagatggag ctctaccgcc1920agaaggtgga gccgctgcgc gcagagctcc aagagggcgc gcgccagaag ctgcacgagc1980tgcaagagaa gctgagccca ctgggcgagg agatgcgcga ccgcgcgcgc gcccatgtgg2040
acgcgctgcg cacgcatctg gccccctaca gcgacgagct gcgccagcgc ttggccgcgc2100gccttgaggc tctcaaggag aacggcggcg ccagactggc cgagtaccac gccaaggcca2160ccgagcatct gagcacgctc agcgagaagg ccaagcccgc gctcgaggac ctccgccaag2220gcctgctgcc cgtgctggag agcttcaagg tcagcttcct gagcgctctc gaggagtaca2280ctaagaagct caacacccag tgaaagctta aataagtatg aactaaaatg catgtaggtg2340taagagctca tggagagcat ggaatattgt atccgaccat gtaacagtat aataactgag2400ctccatctca cttcttctat gaataaacaa aggatgttat gatatattaa cactctatct2460atgcacctta ttgttctatg ataaatttcc tcttattatt ataaatcatc tgaatcgtga2520cggcttatgg aatgcttcaa atagtacaaa aacaaatgtg tactataaga ctttctaaac2580aattctaact ttagcattgt gaacgagaca taagtgttaa gaagacataa caattataat2640ggaagaagtt tgtctccatt tatatattat atattaccca cttatgtatt atattaggat2700gttaaggaga cataacaatt ataaagagag aagtttgtat ccatttatat attatatact2760acccatttat atattatact tatccactta tttaatgtct ttataaggtt tgatccatga2820tatttctaat attttagttg atatgtatat gaaaaggtac tatttgaact ctcttactct2880gtataaaggt tggatcatcc ttaaagtggg tctatttaat tttattgctt cttacagata2940aaaaaaaaat tatgagttgg tttgataaaa tattgaagga tttaaaataa taataaataa3000taaataacat ataatatatg tatataaatt tattataata taacatttat ctataaaaaa3060gtaaatattg tcataaatct atacaatcgt ttagccttgc tggaacgaat ctcaattatt3120taaacgagag taaacatatt tgactttttg gttatttaac aaattattat ttaacactat3180atgaaatttt ttttttttat cagcaaagaa ataaaattaa attaagaagg acaatggtgt3240gtcccaatcc ttatacaacc aacttccaca agaaagtcaa gtcagagaca acaaaaaaac3300aagcaaagga aattttttaa tttgagttgt cttgtttgct gcataattta tgcagtaaaa3360cactacacat aaccctttta gcagtagagc aatggttgac cgtgtgctta gcttctttta3420ttttattttt ttatcagcaa agaataaata aaataaaatg agacacttca gggatgtttc3480aacccttata caaaacccca aaaacaagtt tcctagcacc ctaccaacta a 3531<210>176<211>251<212>PRT<213>Artificial Sequence<220>
<223>Apo22
<400>176Met Gly Arg His Phe Trp Gln Gln Asp Glu Pro Pro Gln Ser Pro Trp1 5 10 15Asp Arg Val Lys Asp Leu Ala Thr Val Tyr Val Asp Val Leu Lys Asp20 25 30Ser Gly Arg Asp Tyr Val Ser Gln Phe Glu Gly Ser Ala Leu Gly Lys35 40 45Gln Leu Asn Leu Lys Leu Leu Asp Asn Trp Asp Ser Val Thr Ser Thr50 55 60Phe Ser Lys Leu Arg Glu Gln Leu Gly Pro Val Thr Gln Glu Phe Trp65 70 75 80Asp Asn Leu Glu Lys Glu Thr Glu Gly Leu Arg Gln Glu Met Ser Lys85 90 95Asp Leu Glu Glu Val Lys Ala Lys Val Gln Pro Tyr Leu Asp Asp Phe100 105 110Gln Lys Lys Trp Gln Glu Glu Met Glu Leu Tyr Arg Gln Lys Val Glu115 120 125Pro Leu Arg Ala Glu Leu Gln Glu Gly Ala Arg Gln Lys Leu His Glu130 135 140Leu Gln Glu Lys Leu Ser Pro Leu Gly Glu Glu Met Arg Asp Arg Ala145 150 155 160Arg Ala His Val Asp Ala Leu Arg Thr His Leu Ala Pro Tyr Ser Asp165 170 175Glu Leu Arg Gln Arg Leu Ala Ala Arg Leu Glu Ala Leu Lys Glu Asn180 185 190Gly Gly Ala Arg Leu Ala Glu Tyr His Ala Lys Ala Thr Glu His Leu195 200 205Ser Thr Leu Ser Glu Lys Ala Lys Pro Ala Leu Glu Asp Leu Arg Gln210 215 220Gly Lau Leu Pro Val Leu Glu Ser Phe Lys Val Ser Phe Leu Ser Ala
225 230 235 240Leu Glu Glu Tyr Thr Lys Lys Leu Asn Thr Gln245 250<210>177<211>36<212>DNA<213>Artificial Sequence<220>
<223>forward primer 1201<400>177gcagcaccat ggggcggcat ttctggcagc aagatg36<210>178<211>4269<212>DNA<213>Artificial Sequence<220>
<223>Apo23<400>178gaattcattg tactcccagt atcattatag tgaaagtttt ggctctctcg ccggtggttt 60tttacctcta tttaaagggg ttttccacct aaaaattctg gtatcattct cactttactt120gttactttaa tttctcataa tctttggttg aaattatcac gcttccgcac acgatatccc180tacaaattta ttatttgtta aacattttca aaccgcataa aattttatga agtcccgtct240atctttaatg tagtctaaca ttttcatatt gaaatatata atttacttaa ttttagcgtt300ggtagaaagc ataaagattt attcttattc ttcttcatat aaatgtttaa tatacaatat360aaacaaattc tttaccttaa gaaggatttc ccattttata ttttaaaaat atatttatca420aatatttttc aaccacgtaa atctcataat aataagttgt ttcaaaagta ataaaattta480actccataat ttttttattc gactgatctt aaagcaacac ccagtgacac aactagccat540ttttttcttt gaataaaaaa atccaattat cattgtattt tttttataca atgaaaattt600caccaaacaa tcatttgtgg tatttctgaa gcaagtcatg ttatgcaaaa ttctataatt660cccatttgac actacggaag taactgaaga tctgctttta catgcgagac acatcttcta720aagtaatttt aataatagtt actatattca agatttcata tatcaaatac tcaatattac780ttctaaaaaa ttaattagat ataattaaaa tattactttt ttaattttaa gtttaattgt840tgaatttgtg actattgatt tattattcta ctatgtttaa attgttttat agatagttta900aagtaaatat aagtaatgta gtagagtgtt agagtgttac cctaaaccat aaactataac960
atttatggtg gactaatttt catatatttc ttattgcttt taccttttct tggtatgtaa1020gtccgtaact agaattacag tgggttgcca tgacactctg tggtcttttg gttcatgcat1080gggtcttgcg caagaaaaag acaaagaaca aagaaaaaag acaaaacaga gagacaaaac1140gcaatcacac aaccaactca aattagtcac tggctgatca agatcgccgc gtccatgtat1200gtctaaatgc catgcaaagc aacacgtgct taacatgcac tttaaatggc tcacccatct1260caacccacac acaaacacat tgcctttttc ttcatcatca ccacaaccac ctgtatatat1320tcattctctt ccgccacctc aatttcttca cttcaacaca cgtcaacctg catatgcgtg1380tcatcccatg cccaaatctc catgcatgtt ccaaccacct tctctcttat ataataccta1440taaatacctc taatatcact cacttctttc atcatccatc catccagagt actactactc1500tactactata ataccccaac ccaactcata ttcaatacta ctctactatg gcggatacag1560ctagaggaac ccatcacgat atcatcggca gagaccagta cccgatgatg ggccgagacc1620gagaccagta ccagatgtcc ggacgaggat ctgactactc caagtctagg cagattgcta1680aagctgcaac tgctgtcaca gctggtggtt ccctccttgt tctctccagc cttacccttg1740ttggaactgt catagctttg actgttgcaa cacctctgct cgttatcttc agcccaatcc1800ttgtcccggc tctcatcaca gttgcactcc tcatcaccgg ttttctttcc tctggagggt1860ttggcattgc cgctataacc gttttctctt ggatttacaa gtaagcacac atttatcatc1920ttacttcata attttgtgca atatgtgcat gcatgtgttg agccagtagc tttggatcaa1980tttttttggt agaataacaa atgtaacaat aagaaattgc aaattctagg gaacatttgg2040ttaactaaat acgaaatttg acctagctag cttgaatgtg tctgtgtata tcatctatat2100aggtaaaatg cttggtatga tacctattga ttgtgaatag gtacgcaacg ggagagcacc2160cacagggatc agacaagttg gacagtgcaa ggatgaagtt gggaagcaaa gctcaggatc2220tgaaagacag agctcagtac tacggacagc aacatactgg tggggaacat gaccgtgacc2280gtactcgtgg tggccagcac actaccatgg atgaaccccc ccagagcccc tgggatcgag2340tgaaggacct ggccactgtg tacgtggatg tgctcaaaga cagcggcaga gactatgtgt2400cccagtttga aggctccgcc ttgggaaaac agctaaacct aaagctcctt gacaactggg2460acagcgtgac ctccaccttc agcaagctgc gcgaacagct cggccctgtg acccaggagt2520tctgggataa cctggaaaag gagacagagg gcctgaggca ggagatgagc aaggatctgg2580aggaggtgaa ggccaaggtg cagccctacc tggacgactt ccagaagaag tggcaggagg2640agatggagct ctaccgccag aaggtggagc cgctgcgcgc agagctccaa gagggcgcgc2700
gccagaagct gcacgagctg caagagaagc tgagcccact gggcgaggag atgcgcgacc2760gcgcgcgcgc ccatgtggac gcgctgcgca cgcatctggc cccctacagc gacgagctgc2820gccagcgctt ggccgcgcgc cttgaggctc tcaaggagaa cggcggcgcc agactggccg2880agtaccacgc caaggccacc gagcatctga gcacgctcag cgagaaggcc aagcccgcgc2940tcgaggacct ccgccaaggc ctgctgcccg tgctggagag cttcaaggtc agcttcctga3000gcgctctcga ggagtacact aagaagctca acacccagtg aaagcttaaa taagtatgaa3060ctaaaatgca tgtaggtgta agagctcatg gagagcatgg aatattgtat ccgaccatgt3120aacagtataa taactgagct ccatctcact tcttctatga ataaacaaag gatgttatga3180tatattaaca ctctatctat gcaccttatt gttctatgat aaatttcctc ttattattat3240aaatcatctg aatcgtgacg gcttatggaa tgcttcaaat agtacaaaaa caaatgtgta3300ctataagact ttctaaacaa ttctaacttt agcattgtga acgagacata agtgttaaga3360agacataaca attataatgg aagaagtttg tctccattta tatattatat attacccact3420tatgtattat attaggatgt taaggagaca taaeaattat aaagagagaa gtttgtatcc3480atttatatat tatatactac ccatttatat attatactta tccacttatt taatgtcttt3540ataaggtttg atccatgata tttctaatat tttagttgat atgtatatga aaaggtacta3600tttgaactct cttactctgt ataaaggttg gatcatcctt aaagtgggtc tatttaattt3660tattgcttct tacagataaa aaaaaaatta tgagttggtt tgataaaata ttgaaggatt3720taaaataata ataaataata aataacatat aatatatgta tataaattta ttataatata3780acatttatct ataaaaaagt aaatattgtc ataaatctat acaatcgttt agccttgctg3840gaacgaatct caattattta aacgagagta aacatatttg actttttggt tatttaacaa3900attattattt aacactatat gaaatttttt ttttttatca gcaaagaaat aaaattaaat3960taagaaggac aatggtgtgt cccaatcctt atacaaccaa cttccacaag aaagtcaagt4020cagagacaac aaaaaaacaa gcaaaggaaa ttttttaatt tgagttgtct tgtttgctgc4080ataatttatg cagtaaaaca ctacacataa cccttttagc agtagagcaa tggttgaccg4140tgtgcttagc ttcttttatt ttattttttt atcagcaaag aataaataaa ataaaatgag4200acacttcagg gatgtttcaa cccttataca aaaccccaaa aacaagtttc ctagcaccct4260accaactaa4269<210>179<211>417<212>PRT<213>Artificial Sequence
<220>
<223>Apo23<400>179Met Ala Asp Thr Ala Arg Gly Thr His His Asp Ile Ile Gly Arg Asp1 5 10 15Gln Tyr Pro Met Met Gly Arg Asp Arg Asp Gln Tyr Gln Met Ser Gly20 25 30Arg Gly Ser Asp Tyr Ser Lys Ser Arg Gln Ile Ala Lys Ala Ala Thr35 40 45Ala Val Thr Ala Gly Gly Ser Leu Leu Val Leu Ser Ser Leu Thr Leu50 55 60Val Gly Thr Val Ile Ala Leu Thr Val Ala Thr Pro Leu Leu Val Ile65 70 75 80Phe Ser Pro Ile Leu Val Pro Ala Leu Ile Thr Val Ala Leu Leu Ile85 90 95Thr Gly Phe Leu Ser Ser Gly Gly Phe Gly Ile Ala Ala Ile Thr Val100 105 110Phe Ser Trp Ile Tyr Lys Tyr Ala Thr Gly Glu His Pro Gln Gly Ser115 120 125Asp Lys Leu Asp Ser Ala Arg Met Lys Leu Gly Ser Lys Ala Gln Asp130 135 140Leu Lys Asp Arg Ala Gln Tyr Tyr Gly Gln Gln His Thr Gly Gly Glu145 150 155 160His Asp Arg Asp Arg Thr Arg Gly Gly Gln His Thr Thr Met Asp Glu165 170 175Pro Pro Gln Ser Pro Trp Asp Arg Val Lys Asp Leu Ala Thr Val Tyr180 185 190Val Asp Val Leu Lys Asp Ser Gly Arg Asp Tyr Val Ser Gln Phe Glu195 200 205Gly Ser Ala Leu Gly Lys Gln Leu Asn Leu Lys Leu Leu Asp Asn Trp
210 215 220Asp Ser Val Thr Ser Thr Phe Ser Lys Leu Arg Glu Gln Leu Gly Pro225 230 235 240Val Thr Gln Glu Phe Trp Asp Asn Leu Glu Lys Glu Thr Glu Gly Leu245 250 255Arg Gln Glu Met Ser Lys Asp Leu Glu Glu Val Lys Ala Lys Val Gln260 265 270Pro Tyr Leu Asp Asp Phe Gln Lys Lys Trp Gln Glu Glu Met Glu Leu275 280 285Tyr Arg Gln Lys Val Glu Pro Leu Arg Ala Glu Leu Gln Glu Gly Ala290 295 300Arg Gln Lys Leu His Glu Leu Gln Glu Lys Leu Ser Pro Leu Gly Glu305 310 315 320Glu Met Arg Asp Arg Ala Arg Ala His Val Asp Ala Leu Arg Thr His325 330 335Leu Ala Pro Tyr Ser Asp Glu Leu Arg Gln Arg Leu Ala Ala Arg Leu340 345 350Glu Ala Leu Lys Glu Asn Gly Gly Ala Arg Leu Ala Glu Tyr His Ala355 360 365Lys Ala Thr Glu His Leu Ser Thr Leu Ser Glu Lys Ala Lys Pro Ala370 375 380Leu Glu Asp Leu Arg Gln Gly Leu Leu Pro Val Leu Glu Ser Phe Lys385 390 395 400Val Ser Phe Leu Ser Ala Leu Glu Glu Tyr Thr Lys Lys Leu Asn Thr405 410 415Gln<210>180<211>4290<212>DNA<213>Artificial Sequence
<220>
<223>Apo24<400>180gaattcattg tactcccagt atcattatag tgaaagtttt ggctctctcg ccggtggttt 60tttacctcta tttaaagggg ttttccacct aaaaattctg gtatcattct cactttactt 120gttactttaa tttctcataa tctttggttg aaattatcac gcttccgcac acgatatccc 180tacaaattta ttatttgtta aacattttca aaccgcataa aattttatga agtcccgtct 240atctttaatg tagtctaaca ttttcatatt gaaatatata atttacttaa ttttagcgtt 300ggtagaaagc ataaagattt attcttattc ttcttcatat aaatgtttaa tatacaatat 360aaacaaattc tttaccttaa gaaggatttc ccattttata ttttaaaaat atatttatca 420aatatttttc aaccacgtaa atctcataat aataagttgt ttcaaaagta ataaaattta 480actccataat ttttttattc gactgatctt aaagcaacac ccagtgacac aactagccat 540ttttttcttt gaataaaaaa atccaattat cattgtattt tttttataca atgaaaattt 600caccaaacaa tcatttgtgg tatttctgaa gcaagtcatg ttatgcaaaa ttctataatt 660cccatttgac actacggaag taactgaaga tctgctttta catgcgagac acatcttcta 720aagtaatttt aataatagtt actatattca agatttcata tatcaaatac tcaatattac 780ttctaaaaaa ttaattagat ataattaaaa tattactttt ttaattttaa gtttaattgt 840tgaatttgtg actattgatt tattattcta ctatgtttaa attgttttat agatagttta 900aagtaaatat aagtaatgta gtagagtgtt agagtgttac cctaaaccat aaactataac 960atttatggtg gactaatttt catatatttc ttattgcttt taccttttct tggtatgtaa1020gtccgtaact agaattacag tgggttgcca tgacactctg tggtcttttg gttcatgcat1080gggtcttgcg caagaaaaag acaaagaaca aagaaaaaag acaaaacaga gagacaaaac1140gcaatcacac aaccaactca aattagtcac tggctgatca agatcgccgc gtccatgtat1200gtctaaatgc catgcaaagc aacacgtgct taacatgcac tttaaatggc tcacccatct1260caacccacac acaaacacat tgcctttttc ttcatcatca ccacaaccac ctgtatatat1320tcattctctt ccgccacctc aatttcttca cttcaacaca cgtcaacctg catatgcgtg1380tcatcccatg cccaaatctc catgcatgtt ccaaccacct tctctcttat ataataccta1440taaatacctc taatatcact cacttctttc atcatccatc catccagagt actactactc1500tactactata ataccccaac ccaactcata ttcaatacta ctctactatg gcggatacag1560ctagaggaac ccatcacgat atcatcggca gagaccagta cccgatgatg ggccgagacc1620
gagaccagta ccagatgtcc ggacgaggat ctgactactc caagtctagg cagattgcta1680aagctgcaac tgctgtcaca gctggtggtt ccctccttgt tctctccagc cttacccttg1740ttggaactgt catagctttg actgttgcaa cacctctgct cgttatcttc agcccaatcc1800ttgtcccggc tctcatcaca gttgcactcc tcatcaccgg ttttctttcc tctggagggt1860ttggcattgc cgctataacc gttttctctt ggatttacaa gtaagcacac atttatcatc1920ttacttcata attttgtgca atatgtgcat gcatgtgttg agccagtagc tttggatcaa1980tttttttggt agaataacaa atgtaacaat aagaaattgc aaattctagg gaacatttgg2040ttaactaaat acgaaatttg acctagctag cttgaatgtg tctgtgtata tcatctatat2100aggtaaaatg cttggtatga tacctattga ttgtgaatag gtacgcaacg ggagagcacc2160cacagggatc agacaagttg gacagtgcaa ggatgaagtt gggaagcaaa gctcaggatc2220tgaaagacag agctcagtac tacggacagc aacatactgg tggggaacat gaccgtgacc2280gtactcgtgg tggccagcac actaccatgg ggcggcattt ctggcagcaa gatgaacccc2340cccagagccc ctgggatcga gtgaaggacc tggccactgt gtacgtggat gtgctcaaag2400acagcggcag agactatgtg tcccagtttg aaggctccgc cttgggaaaa cagctaaacc2460taaagctcct tgacaactgg gacagcgtga cctccacctt cagcaagctg cgcgaacagc2520tcggccctgt gacccaggag ttctgggata acctggaaaa ggagacagag ggcctgaggc2580aggagatgag caaggatctg gaggaggtga aggccaaggt gcagccctac ctggacgact2640tccagaagaa gtggcaggag gagatggagc tctaccgcca gaaggtggag ccgctgcgcg2700cagagctcca agagggcgcg cgccagaagc tgcacgagct gcaagagaag ctgagcccac2760tgggcgagga gatgcgcgac cgcgcgcgcg cccatgtgga cgcgctgcgc acgcatctgg2820ccccctacag cgacgagctg cgccagcgct tggccgcgcg ccttgaggct ctcaaggaga2880acggcggcgc cagactggcc gagtaccacg ccaaggccac cgagcatctg agcacgctca2940gcgagaaggc caagcccgcg ctcgaggacc tccgccaagg cctgctgccc gtgctggaga3000gcttcaaggt cagcttcctg agcgctctcg aggagtacac taagaagctc aacacccagt3060gaaagcttaa ataagtatga actaaaatgc atgtaggtgt aagagctcat ggagagcatg3120gaatattgta tccgaccatg taacagtata ataactgagc tccatctcac ttcttctatg3180aataaacaaa ggatgttatg atatattaac actctatcta tgcaccttat tgttctatga3240taaatttcct cttattatta taaatcatct gaatcgtgac ggcttatgga atgcttcaaa3300tagtacaaaa acaaatgtgt actataagac tttctaaaca attctaactt tagcattgtg3360aacgagacat aagtgttaag aagacataac aattataatg gaagaagttt gtctccattt3420
atatattata tattacccac ttatgtatta tattaggatg ttaaggagac ataacaatta3480taaagagaga agtttgtatc catttatata ttatatacta cccatttata tattatactt3540atccacttat ttaatgtctt tataaggttt gatccatgat atttctaata ttttagttga3600tatgtatatg aaaaggtact atttgaactc tcttactctg tataaaggtt ggatcatcct3660taaagtgggt ctatttaatt ttattgcttc ttacagataa aaaaaaaatt atgagttggt3720ttgataaaat attgaaggat ttaaaataat aataaataat aaataacata taatatatgt3780atataaattt attataatat aacatttatc tataaaaaag taaatattgt cataaatcta3840tacaatcgtt tagccttgct ggaacgaatc tcaattattt aaacgagagt aaacatattt3900gactttttgg ttatttaaca aattattatt taacactata tgaaattttt tttttttatc3960agcaaagaaa taaaattaaa ttaagaagga caatggtgtg tcccaatcct tatacaacca4020acttccacaa gaaagtcaag tcagagacaa caaaaaaaca agcaaaggaa attttttaat4080ttgagttgtc ttgtttgctg cataatttat gcagtaaaac actacacata acccttttag4140cagtagagca atggttgacc gtgtgcttag cttcttttat tttatttttt tatcagcaaa4200gaataaataa aataaaatga gacacttcag ggatgtttca acccttatac aaaaccccaa4260aaacaagttt cctagcaccc taccaactaa 4290<210>181<211>424<212>PRT<213>Artificial Sequence<220>
<223>Apo24<400>181Met Ala Asp Thr Ala Arg Gly Thr His His Asp Ile Ile Gly Arg Asp1 5 10 15Gln Tyr Pro Met Met Gly Arg Asp Arg Asp Gln Tyr Gln Met Ser Gly20 25 30Arg Gly Ser Asp Tyr Ser Lys Ser Arg Gln Ile Ala Lys Ala Ala Thr35 40 45Ala Val Thr Ala Gly Gly Ser Leu Leu Val Leu Ser Ser Leu Thr Leu50 55 60Val Gly Thr Val Ile Ala Leu Thr Val Ala Thr Pro Leu Leu Val Ile
65 70 75 80Phe Ser Pro Ile Leu Val Pro Ala Leu Ile Thr Val Ala Leu Leu Ile85 90 95Thr Gly Phe Leu Ser Ser Gly Gly Phe Gly Ile Ala Ala Ile Thr Val100 105 110Phe Ser Trp Ile Tyr Lys Tyr Ala Thr Gly Glu His Pro Gln Gly Ser115 120 125Asp Lys Leu Asp Ser Ala Arg Met Lys Leu Gly Ser Lys Ala Gln Asp130 135 140Leu Lys Asp Arg Ala Gln Tyr Tyr Gly Gln Gln His Thr Gly Gly Glu145 150 155 160His Asp Arg Asp Arg Thr Arg Gly Gly Gln His Thr Thr Met Gly Arg165 170 175His Phe Trp Gln Gln Asp Glu Pro Pro Gln Ser Pro Trp Asp Arg Val180 185 190Lys Asp Leu Ala Thr Val Tyr Val Asp Val Leu Lys Asp Ser Gly Arg195 200 205Asp Tyr Val Ser Gln Phe Glu Gly Ser Ala Leu Gly Lys Gln Leu Asn210 215 220Leu Lys Leu Leu Asp Asn Trp Asp Ser Val Thr Ser Thr Phe Ser Lys225 230 235 240Leu Arg Glu Gln Leu Gly Pro Val Thr Gln Glu Phe Trp Asp Asn Leu245 250 255Glu Lys Glu Thr Glu Gly Leu Arg Gln Glu Met Ser Lys Asp Leu Glu260 265 270Glu Val Lys Ala Lys Val Gln Pro Tyr Leu Asp Asp Phe Gln Lys Lys275 280 285Trp Gln Glu Glu Met Glu Leu Tyr Arg Gln Lys Val Glu Pro Leu Arg290 295 300
Ala Glu Leu Gln Glu Gly Ala Arg Gln Lys Leu His Glu Leu Gln Glu305 310 315 320Lys Leu Ser Pro Leu Gly Glu Glu Met Arg Asp Arg Ala Arg Ala His325 330 335Val Asp Ala Leu Arg Thr His Leu Ala Pro Tyr Ser Asp Glu Leu Arg340 345 350Gln Arg Leu Ala Ala Arg Leu Glu Ala Leu Lys Glu Asn Gly Gly Ala355 360 365Arg Leu Ala Glu Tyr His Ala Lys Ala Thr Glu His Leu Ser Thr Leu370 375 380Ser Glu Lys Ala Lys Pro Ala Leu Glu Asp Leu Arg Gln Gly Leu Leu385 390 395 400Pro Val Leu Glu Ser Phe Lys Val Ser Phe Leu Ser Ala Leu Glu Glu405 410 415Tyr Thr Lys Lys Leu Asn Thr Gln420<210>182<211>4389<212>DNA<213>Artificial Sequence<220>
<223>Apo25<400>182gaattcattg tactcccagt atcattatag tgaaagtttt ggctctctcg ccggtggttt 60tttacctcta tttaaagggg ttttccacct aaaaattctg gtatcattct cactttactt120gttactttaa tttctcataa tctttggttg aaattatcac gcttccgcac acgatatccc180tacaaattta ttatttgtta aacattttca aaccgcataa aattttatga agtcccgtct240atctttaatg tagtctaaca ttttcatatt gaaatatata atttacttaa ttttagcgtt300ggtagaaagc ataaagattt attcttattc ttcttcatat aaatgtttaa tatacaatat360aaacaaattc tttaccttaa gaaggatttc ccattttata ttttaaaaat atatttatca420aatatttttc aaccacgtaa atctcataat aataagttgt ttcaaaagta ataaaattta480actccataat ttttttattc gactgatctt aaagcaacac ccagtgacac aactagccat540
ttttttcttt gaataaaaaa atccaattat cattgtattt tttttataca atgaaaattt 600caccaaacaa tcatttgtgg tatttctgaa gcaagtcatg ttatgcaaaa ttctataatt 660cccatttgac actacggaag taactgaaga tctgctttta catgcgagac acatcttcta 720aagtaatttt aataatagtt actatattca agatttcata tatcaaatac tcaatattac 780ttctaaaaaa ttaattagat ataattaaaa tattactttt ttaattttaa gtttaattgt 840tgaatttgtg actattgatt tattattcta ctatgtttaa attgttttat agatagttta 900aagtaaatat aagtaatgta gtagagtgtt agagtgttac cctaaaccat aaactataac 960atttatggtg gactaatttt catatatttc ttattgcttt taccttttct tggtatgtaa1020gtccgtaact agaattacag tgggttgcca tgacactctg tggtcttttg gttcatgcat1080gggtcttgcg caagaaaaag acaaagaaca aagaaaaaag acaaaacaga gagacaaaac1140gcaatcacac aaccaactca aattagtcac tggctgatca agatcgccgc gtccatgtat1200gtctaaatgc catgcaaagc aacacgtgct taacatgcac tttaaatggc tcacccatct1260caacccacac acaaacacat tgcctttttc ttcatcatca ccacaaccac ctgtatatat1320tcattctctt ccgccacctc aatttcttca cttcaacaca cgtcaacctg catatgcgtg1380tcatcccatg cccaaatctc catgcatgtt ccaaccacct tctctcttat ataataccta1440taaatacctc taatatcact cacttctttc atcatccatc catccagagt actactactc1500tactactata ataccccaac ccaactcata ttcaatacta ctctactatg gcggatacag1560ctagaggaac ccatcacgat atcatcggca gagaccagta cccgatgatg ggccgagacc1620gagaccagta ccagatgtcc ggacgaggat ctgactactc caagtctagg cagattgcta1680aagctgcaac tgctgtcaca gctggtggtt ccctccttgt tctctccagc cttacccttg1740ttggaactgt catagctttg actgttgcaa cacctctgct cgttatcttc agcccaatcc1800ttgtcccggc tctcatcaca gttgcactcc tcatcaccgg ttttctttcc tctggagggt1860ttggcattgc cgctataacc gttttctctt ggatttacaa gtaagcacac atttatcatc1920ttacttcata attttgtgca atatgtgcat gcatgtgttg agccagtagc tttggatcaa1980tttttttggt agaataacaa atgtaacaat aagaaattgc aaattctagg gaacatttgg2040ttaactaaat acgaaatttg acctagctag cttgaatgtg tctgtgtata tcatctatat2100aggtaaaatg cttggtatga tacctattga ttgtgaatag gtacgcaacg ggagagcacc2160cacagggatc agacaagttg gacagtgcaa ggatgaagtt gggaagcaaa gctcaggatc2220tgaaagacag agctcagtac tacggacagc aacatactgg tggggaacat gaccgtgacc2280gtactcgtgg tggccagcac actaccatgg ctgagatcac ccgcattcct ctctacaaag2340
gtaagtctct ccgtaaggcg ctgaaggaac atggacttct agaagacttc ttgcagaaac2400aacagtatgg catctcgagc aagttcatgg atgaaccccc ccagagcccc tgggatcgag2460tgaaggacct ggccactgtg tacgtggatg tgctcaaaga cagcggcaga gactatgtgt2520cccagtttga aggctccgcc ttgggaaaac agctaaacct aaagctcctt gacaactggg2580acagcgtgac ctccaccttc agcaagctgc gcgaacagct cggccctgtg acccaggagt2640tctgggataa cctggaaaag gagacagagg gcctgaggca ggagatgagc aaggatctgg2700aggaggtgaa ggccaaggtg cagccctacc tggacgactt ccagaagaag tggcaggagg2760agatggagct ctaccgccag aaggtggagc cgctgcgcgc agagctccaa gagggcgcgc2820gccagaagct gcacgagctg caagagaagc tgagcccact gggcgaggag atgcgcgacc2880gcgcgcgcgc ccatgtggac gcgctgcgca cgcatctggc cccctacagc gacgagctgc2940gccagcgctt ggccgcgcgc cttgaggctc tcaaggagaa cggcggcgcc agactggccg3000agtaccacgc caaggccacc gagcatctga gcacgctcag cgagaaggcc aagcccgcgc3060tcgaggacct ccgccaaggc ctgctgcccg tgctggagag cttcaaggtc agcttcctga3120gcgctctcga ggagtacact aagaagctca acacccagtg aaagcttaaa taagtatgaa3180ctaaaatgca tgtaggtgta agagctcatg gagagcatgg aatattgtat ccgaccatgt3240aacagtataa taactgagct ccatctcact tcttctatga ataaacaaag gatgttatga3300tatattaaca ctctatctat gcaccttatt gttctatgat aaatttcctc ttattattat3360aaatcatctg aatcgtgacg gcttatggaa tgcttcaaat agtacaaaaa caaatgtgta3420ctataagact ttctaaacaa ttctaacttt agcattgtga acgagacata agtgttaaga3480agacataaca attataatgg aagaagtttg tctccattta tatattatat attacccact3540tatgtattat attaggatgt taaggagaca taacaattat aaagagagaa gtttgtatcc3600atttatatat tatatactac ccatttatat attatactta tccacttatt taatgtcttt3660ataaggtttg atccatgata tttctaatat tttagttgat atgtatatga aaaggtacta3720tttgaactct cttactctgt ataaaggttg gatcatcctt aaagtgggtc tatttaattt3780tattgcttct tacagataaa aaaaaaatta tgagttggtt tgataaaata ttgaaggatt3840taaaataata ataaataata aataacatat aatatatgta tataaattta ttataatata3900acatttatct ataaaaaagt aaatattgtc ataaatctat acaatcgttt agccttgctg3960gaacgaatct caattattta aacgagagta aacatatttg actttttggt tatttaacaa4020attattattt aacactatat gaaatttttt ttttttatca gcaaagaaat aaaattaaat4080
taagaaggac aatggtgtgt cccaatcctt atacaaccaa cttccacaag aaagtcaagt4140cagagacaac aaaaaaacaa gcaaaggaaa ttttttaatt tgagttgtct tgtttgctgc4200ataatttatg cagtaaaaca ctacacataa cccttttagc agtagagcaa tggttgaccg4260tgtgcttagc ttcttttatt ttattttttt atcagcaaag aataaataaa ataaaatgag4320acacttcagg gatgtttcaa cccttataca aaaccccaaa aacaagtttc ctagcaccct4380accaactaa4389<210>183<211>457<212>PRT<213>Artificial Sequence<220>
<223>Apo25<400>183Met Ala Asp Thr Ala Arg Gly Thr His His Asp Ile Ile Gly Arg Asp1 5 10 15Gln Tyr Pro Met Met Gly Arg Asp Arg Asp Gln Tyr Gln Met Ser Gly20 25 30Arg Gly Ser Asp Tyr Ser Lys Ser Arg Gln Ile Ala Lys Ala Ala Thr35 40 45Ala Val Thr Ala Gly Gly Ser Leu Leu Val Leu Ser Ser Leu Thr Leu50 55 60Val Gly Thr Val Ile Ala Leu Thr Val Ala Thr Pro Leu Leu Val Ile65 70 75 80Phe Ser Pro Ile Leu Val Pro Ala Leu Ile Thr Val Ala Leu Leu Ile85 90 95Thr Gly Phe Leu Ser Ser Gly Gly Phe Gly Ile Ala Ala Ile Thr Val100 105 110Phe Ser Trp Ile Tyr Lys Tyr Ala Thr Gly Glu His Pro Gln Gly Ser115 120 125Asp Lys Leu Asp Ser Ala Arg Met Lys Leu Gly Ser Lys Ala Gln Asp130 135 140
Leu Lys Asp Arg Ala Gln Tyr Tyr Gly Gln Gln His Thr Gly Gly Glu145 150 155 160His Asp Arg Asp Arg Thr Arg Gly Gly Gln His Thr Thr Met Ala Glu165 170 175Ile Thr Arg Ile Pro Leu Tyr Lys Gly Lys Ser Leu Arg Lys Ala Leu180 185 190Lys Glu His Gly Leu Leu Glu Asp Phe Leu Gln Lys Gln Gln Tyr Gly195 200 205Ile Ser Ser Lys Phe Met Asp Glu Pro Pro Gln Ser Pro Trp Asp Arg210 215 220Val Lys Asp Leu Ala Thr Val Tyr Val Asp Val Leu Lys Asp Ser Gly225 230 235 240Arg Asp Tyr Val Ser Gln Phe Glu Gly Ser Ala Leu Gly Lys Gln Leu245 250 255Asn Leu Lys Leu Leu Asp Asn Trp Asp Ser Val Thr Ser Thr Phe Ser260 265 270Lys Leu Arg Glu Gln Leu Gly Pro Val Thr Gln Glu Phe Trp Asp Asn275 280 285Leu Glu Lys Glu Thr Glu Gly Leu Arg Gln Glu Met Ser Lys Asp Leu290 295 300Glu Glu Val Lys Ala Lys Val Gln Pro Tyr Leu Asp Asp Phe Gln Lys305 310 315 320Lys Trp Gln Glu Glu Met Glu Leu Tyr Arg Gln Lys Val Glu Pro Leu325 330 335Arg Ala Glu Leu Gln Glu Gly Ala Arg Gln Lys Leu His Glu Leu Gln340 345 350Glu Lys Leu Ser Pro Leu Gly Glu Glu Met Arg Asp Arg Ala Arg Ala355 360 365His Val Asp Ala Leu Arg Thr His Leu Ala Pro Tyr Ser Asp Glu Leu370 375 380
Arg Gln Arg Leu Ala Ala Arg Leu Glu Ala Leu Lys Glu Asu Gly Gly385 390 395 400Ala Arg Leu Ala Glu Tyr His Ala Lys Ala Thr Glu His Leu Ser Thr405 410 415Leu Ser Glu Lys Ala Lys Pro Ala Leu Glu Asp Leu Arg Gln Gly Leu420 425 430Leu Pro Val Leu Glu Ser Phe Lys Val Ser Phe Leu Ser Ala Leu Glu435 440 445Glu Tyr Thr Lys Lys Leu Asn Thr Gln450 455<210>184<211>4410<212>DNA<213>Artificial Sequence<220>
<223>Apo26<400>184gaattcattg tactcccagt atcattatag tgaaagtttt ggctctctcg ccggtggttt 60tttacctcta tttaaagggg ttttccacct aaaaattctg gtatcattct cactttactt120gttactttaa tttctcataa tctttggttg aaattatcac gcttccgcac acgatatccc180tacaaattta ttatttgtta aacattttca aaccgcataa aattttatga agtcccgtct240atctttaatg tagtctaaca ttttcatatt gaaatatata atttacttaa ttttagcgtt300ggtagaaagc ataaagattt attcttattc ttcttcatat aaatgtttaa tatacaatat360aaacaaattc tttaccttaa gaaggatttc ccattttata ttttaaaaat atatttatca420aatatttttc aaccacgtaa atctcataat aataagttgt ttcaaaagta ataaaattta480actccataat ttttttattc gactgatctt aaagcaacac ccagtgacac aactagccat540ttttttcttt gaataaaaaa atccaattat cattgtattt tttttataca atgaaaattt600caccaaacaa tcatttgtgg tatttctgaa gcaagtcatg ttatgcaaaa ttctataatt660cccatttgac actacggaag taactgaaga tctgctttta catgcgagac acatcttcta720aagtaatttt aataatagtt actatattca agatttcata tatcaaatac tcaatattac780ttctaaaaaa ttaattagat ataattaaaa tattactttt ttaattttaa gtttaattgt840tgaatttgtg actattgatt tattattcta ctatgtttaa attgttttat agatagttta900
aagtaaatat aagtaatgta gtagagtgtt agagtgttac cctaaaccat aaactataac 960atttatggtg gactaatttt catatatttc ttattgcttt taccttttct tggtatgtaa1020gtccgtaact agaattacag tgggttgcca tgacactctg tggtcttttg gttcatgcat1080gggtcttgcg caagaaaaag acaaagaaca aagaaaaaag acaaaacaga gagacaaaac1140gcaatcacac aaccaactca aattagtcac tggctgatca agatcgccgc gtccatgtat1200gtctaaatgc catgcaaagc aacacgtgct taacatgcac tttaaatggc tcacccatct1260caacccacac acaaacacat tgcctttttc ttcatcatca ccacaaccac ctgtatatat1320tcattctctt ccgccacctc aatttcttca cttcaacaca cgtcaacctg catatgcgtg1380tcatcccatg cccaaatctc catgcatgtt ccaaccacct tctctcttat ataataccta1440taaatacctc taatatcact cacttctttc atcatccatc catccagagt actactactc1500tactactata ataccccaac ccaactcata ttcaatacta ctctactatg gcggatacag1560ctagaggaac ccatcacgat atcatcggca gagaccagta cccgatgatg ggccgagacc1620gagaccagta ccagatgtcc ggacgaggat ctgactactc caagtctagg cagattgcta1680aagctgcaac tgctgtcaca gctggtggtt ccctccttgt tctctccagc cttacccttg1740ttggaactgt catagctttg actgttgcaa cacctctgct cgttatcttc agcccaatcc1800ttgtcccggc tctcatcaca gttgcactcc tcatcaccgg ttttctttcc tctggagggt1860ttggcattgc cgctataacc gttttctctt ggatttacaa gtaagcacac atttatcatc1920ttacttcata attttgtgca atatgtgcat gcatgtgttg agccagtagc tttggatcaa1980tttttttggt agaataacaa atgtaacaat aagaaattgc aaattctagg gaacatttgg2040ttaactaaat acgaaatttg acctagctag cttgaatgtg tctgtgtata tcatctatat2100aggtaaaatg cttggtatga tacctattga ttgtgaatag gtacgcaacg ggagagcacc2160cacagggatc agacaagttg gacagtgcaa ggatgaagtt gggaagcaaa gctcaggatc2220tgaaagacag agctcagtac tacggacagc aacatactgg tggggaacat gaccgtgacc2280gtactcgtgg tggccagcac actaccatgg ctgagatcac ccgcattcct ctctacaaag2340gtaagtctct ccgtaaggcg ctgaaggaac atggacttct agaagacttc ttgcagaaac2400aacagtatgg catctcgagc aagttcatgg ggcggcattt ctggcagcaa gatgaacccc2460cccagagccc ctgggatcga gtgaaggacc tggccactgt gtacgtggat gtgctcaaag2520acagcggcag agactatgtg tcccagtttg aaggctccgc cttgggaaaa cagctaaacc2580taaagctcct tgacaactgg gacagcgtga cctccacctt cagcaagctg cgcgaacagc2640
tcggccctgt gacccaggag ttctgggata acctggaaaa ggagacagag ggcctgaggc2700aggagatgag caaggatctg gaggaggtga aggccaaggt gcagccctac ctggacgact2760tccagaagaa gtggcaggag gagatggagc tctaccgcca gaaggtggag ccgctgcgcg2820cagagctcca agagggcgcg cgccagaagc tgcacgagct gcaagagaag ctgagcccac2880tgggcgagga gatgcgcgac cgcgcgcgcg cccatgtgga cgcgctgcgc acgcatctgg2940ccccctacag cgacgagctg cgccagcgct tggccgcgcg ccttgaggct ctcaaggaga3000acggcggcgc cagactggcc gagtaccacg ccaaggccac cgagcatctg agcacgctca3060gcgagaaggc caagcccgcg ctcgaggacc tccgccaagg cctgctgccc gtgctggaga3120gcttcaaggt cagcttcctg agcgctctcg aggagtacac taagaagctc aacacccagt3180gaaagcttaa ataagtatga actaaaatgc atgtaggtgt aagagctcat ggagagcatg3240gaatattgta tccgaccatg taacagtata ataactgagc tccatctcac ttcttctatg3300aataaacaaa ggatgttatg atatattaac actctatcta tgcaccttat tgttctatga3360taaatttcct cttattatta taaatcatct gaatcgtgac ggcttatgga atgcttcaaa3420tagtacaaaa acaaatgtgt actataagac tttctaaaca attctaactt tagcattgtg3480aacgagacat aagtgttaag aagacataac aattataatg gaagaagttt gtctccattt3540atatattata tattacccac ttatgtatta tattaggatg ttaaggagac ataacaatta3600taaagagaga agtttgtatc catttatata ttatatacta cccatttata tattatactt3660atccacttat ttaatgtctt tataaggttt gatccatgat atttctaata ttttagttga3720tatgtatatg aaaaggtact atttgaactc tcttactctg tataaaggtt ggatcatcct3780taaagtgggt ctatttaatt ttattgcttc ttacagataa aaaaaaaatt atgagttggt3840ttgataaaat attgaaggat ttaaaataat aataaataat aaataacata taatatatgt3900atataaattt attataatat aacatttatc tataaaaaag taaatattgt cataaatcta3960tacaatcgtt tagccttgct ggaacgaatc tcaattattt aaacgagagt aaacatattt4020gactttttgg ttatttaaca aattattatt taacactata tgaaattttt tttttttatc4080agcaaagaaa taaaattaaa ttaagaagga caatggtgtg tcccaatcct tatacaacca4140acttccacaa gaaagtcaag tcagagacaa caaaaaaaca agcaaaggaa attttttaat4200ttgagttgtc ttgtttgctg cataatttat gcagtaaaac actacacata acccttttag4260cagtagagca atggttgacc gtgtgcttag cttcttttat tttatttttt tatcagcaaa4320gaataaataa aataaaatga gacacttcag ggatgtttca acccttatac aaaaccccaa4380aaacaagttt cctagcaccc taccaactaa 4410
<210>185<211>464<212>PRT<213>Artificial Sequence<220>
<223>Apo26<400>185Met Ala Asp Thr Ala Arg Gly Thr His His Asp Ile Ile Gly Arg Asp1 5 10 15Gln Tyr Pro Met Met Gly Arg Asp Arg Asp Gln Tyr Gln Met Ser Gly20 25 30Arg Gly Ser Asp Tyr Ser Lys Ser Arg Gln Ile Ala Lys Ala Ala Thr35 40 45Ala Val Thr Ala Gly Gly Ser Leu Leu Val Leu Ser Ser Leu Thr Leu50 55 60Val Gly Thr Val Ile Ala Leu Thr Val Ala Thr Pro Leu Leu Val Ile65 70 75 80Phe Ser Pro Ile Leu Val Pro Ala Leu Ile Thr Val Ala Leu Leu Ile85 90 95Thr Gly Phe Leu Ser Ser Gly Gly Phe Gly Ile Ala Ala Ile Thr Val100 105 110Phe Ser Trp Ile Tyr Lys Tyr Ala Thr Gly Glu His Pro Gln Gly Ser115 120 125Asp Lys Leu Asp Ser Ala Arg Met Lys Leu Gly Ser Lys Ala Gln Asp130 135 140Leu Lys Asp Arg Ala Gln Tyr Tyr Gly Gln Gln His Thr Gly Gly Glu145 150 155 160His Asp Arg Asp Arg Thr Arg Gly Gly Gln His Thr Thr Met Ala Glu165 170 175Ile Thr Arg Ile Pro Leu Tyr Lys Gly Lys Ser Leu Arg Lys Ala Leu180 185 190
Lys Glu His Gly Leu Leu Glu Asp Phe Leu Gln Lys Gln Gln Tyr Gly195 200 205Ile Ser Ser Lys Phe Met Gly Arg His Phe Trp Gln Gln Asp Glu Pro210 215 220Pro Gln Ser Pro Trp Asp Arg Val Lys Asp Leu Ala Thr Val Tyr Val225 230 235 240Asp Val Leu Lys Asp Ser Gly Arg Asp Tyr Val Ser Gln Phe Glu Gly245 250 255Ser Ala Leu Gly Lys Gln Leu Asn Leu Lys Leu Leu Asp Asn Trp Asp260 265 270Ser Val Thr Ser Thr Phe Ser Lys Leu Arg Glu Gln Leu Gly Pro Val275 280 285Thr Gln Glu Phe Trp Asp Asn Leu Glu Lys Glu Thr Glu Gly Leu Arg290 295 300Gln Glu Met Ser Lys Asp Leu Glu Glu Val Lys Ala Lys Val Gln Pro305 310 315 320Tyr Leu Asp Asp Phe Gln Lys Lys Trp Gln Glu Glu Met Glu Leu Tyr325 330 335Arg Gln Lys Val Glu Pro Leu Arg Ala Glu Leu Gln Glu Gly Ala Arg340 345 350Gln Lys Leu His Glu Leu Gln Glu Lys Leu Ser Pro Leu Gly Glu Glu355 360 365Met Arg Asp Arg Ala Arg Ala His Val Asp Ala Leu Arg Thr His Leu370 375 380Ala Pro Tyr Ser Asp Glu Leu Arg Gln Arg Leu Ala Ala Arg Leu Glu385 390 395 400Ala Leu Lys Glu Asn Gly Gly Ala Arg Leu Ala Glu Tyr His Ala Lys405 410 415Ala Thr Glu His Leu Ser Thr Leu Ser Glu Lys Ala Lys Pro Ala Leu420 425 430
Glu Asp Leu Arg Gln Gly Leu Leu Pro Val Leu Glu Ser Phe Lys Val435 440 445Ser Phe Leu Ser Ala Leu Glu Glu Tyr Thr Lys Lys Leu Asn Thr Gln450 455 460<210>186<211>4386<212>DNA<213>Artificial Sequence<220>
<223>Apo27<400>186gaattcattg tactcccagt atcattatag tgaaagtttt ggctctctcg ccggtggttt 60tttacctcta tttaaagggg ttttccacct aaaaattctg gtatcattct cactttactt 120gttactttaa tttctcataa tctttggttg aaattatcac gcttccgcac acgatatccc 180tacaaattta ttatttgtta aacattttca aaccgcataa aattttatga agtcccgtct 240atctttaatg tagtctaaca ttttcatatt gaaatatata atttacttaa ttttagcgtt 300ggtagaaagc ataaagattt attcttattc ttcttcatat aaatgtttaa tatacaatat 360aaacaaattc tttaccttaa gaaggatttc ccattttata ttttaaaaat atatttatca 420aatatttttc aaccacgtaa atctcataat aataagttgt ttcaaaagta ataaaattta 480actccataat ttttttattc gactgatctt aaagcaacac ccagtgacac aactagccat 540ttttttcttt gaataaaaaa atccaattat cattgtattt tttttataca atgaaaattt 600caccaaacaa tcatttgtgg tatttctgaa gcaagtcatg ttatgcaaaa ttctataatt 660cccatttgac actacggaag taactgaaga tctgctttta catgcgagac acatcttcta 720aagtaatttt aataatagtt actatattca agatttcata tatcaaatac tcaatattac 780ttctaaaaaa ttaattagat ataattaaaa tattactttt ttaattttaa gtttaattgt 840tgaatttgtg actattgatt tattattcta ctatgtttaa attgttttat agatagttta 900aagtaaatat aagtaatgta gtagagtgtt agagtgttac cctaaaccat aaactataac 960atttatggtg gactaatttt catatatttc ttattgcttt taccttttct tggtatgtaa1020gtccgtaact agaattacag tgggttgcca tgacactctg tggtcttttg gttcatgcat1080gggtcttgcg caagaaaaag acaaagaaca aagaaaaaag acaaaacaga gagacaaaac1140gcaatcacac aaccaactca aattagtcac tggctgatca agatcgccgc gtccatgtat1200
gtctaaatgc catgcaaagc aacacgtgct taacatgcac tttaaatggc tcacccatct1260caacccacac acaaacacat tgcctttttc ttcatcatca ccacaaccac ctgtatatat1320tcattctctt ccgccacctc aatttcttca cttcaacaca cgtcaacctg catatgcgtg1380tcatcccatg cccaaatctc catgcatgtt ccaaccacct tctctcttat ataataccta1440taaatacctc taatatcact cacttctttc atcatccatc catccagagt actactactc1500tactactata ataccccaac ccaactcata ttcaatacta ctctactatg gcggatacag1560ctagaggaac ccatcacgat atcatcggca gagaccagta cccgatgatg ggccgagacc1620gagaccagta ccagatgtcc ggacgaggat ctgactactc caagtctagg cagattgcta1680aagctgcaac tgctgtcaca gctggtggtt ccctccttgt tctctccagc cttacccttg1740ttggaactgt catagctttg actgttgcaa cacctctgct cgttatcttc agcccaatcc1800ttgtcccggc tctcatcaca gttgcactcc tcatcaccgg ttttctttcc tctggagggt1860ttggcattgc cgctataacc gttttctctt ggatttacaa gtaagcacac atttatcatc1920ttacttcata attttgtgca atatgtgcat gcatgtgttg agccagtagc tttggatcaa1980tttttttggt agaataacaa atgtaacaat aagaaattgc aaattctagg gaacatttgg2040ttaactaaat acgaaatttg acctagctag cttgaatgtg tctgtgtata tcatctatat2100aggtaaaatg cttggtatga tacctattga ttgtgaatag gtacgcaacg ggagagcacc2160cacagggatc agacaagttg gacagtgcaa ggatgaagtt gggaagcaaa gctcaggatc2220tgaaagacag agctcagtac tacggacagc aacatactgg tggggaacat gaccgtgacc2280gtactcgtgg tggccagcac actaccatgg ctgagatcac ccgcattcct ctctacaaag2340gtaagtctct ccgtaaggcg ctgaaggaac atggacttct agaagacttc ttgcagaaac2400aacagtatgg catctcgagc aagttcgatg aaccccccca gagcccctgg gatcgagtga2460aggacctggc cactgtgtac gtggatgtgc tcaaagacag cggcagagac tatgtgtccc2520agtttgaagg ctccgccttg ggaaaacagc taaacctaaa gctccttgac aactgggaca2580gcgtgacctc caccttcagc aagctgcgcg aacagctcgg ccctgtgacc caggagttct2640gggataacct ggaaaaggag acagagggcc tgaggcagga gatgagcaag gatctggagg2700aggtgaaggc caaggtgcag ccctacctgg acgacttcca gaagaagtgg caggaggaga2760tggagctcta ccgccagaag gtggagccgc tgcgcgcaga gctccaagag ggcgcgcgcc2820agaagctgca cgagctgcaa gagaagctga gcccactggg cgaggagatg cgcgaccgcg2880cgcgcgccca tgtggacgcg ctgcgcacgc atctggcccc ctacagcgac gagctgcgcc2940agcgcttggc cgcgcgcctt gaggctctca aggagaacgg cggcgccaga ctggccgagt3000
accacgccaa ggccaccgag catctgagca cgctcagcga gaaggccaag cccgcgctag3060aggacctccg ccaaggcctg ctgcccgtgc tggagagctt caaggtcagc ttcctgagcg3120ctctggagga gtacactaag aagctcaaca cccagtgaaa gcttaaataa gtatgaacta3180aaatgcatgt aggtgtaaga gctcatggag agcatggaat attgtatccg accatgtaac3240agtataataa ctgagctcca tctcacttct tctatgaata aacaaaggat gttatgatat3300attaacactc tatctatgca ccttattgtt ctatgataaa tttcctctta ttattataaa3360tcatctgaat cgtgacggct tatggaatgc ttcaaatagt acaaaaacaa atgtgtacta3420taagactttc taaacaattc taactttagc attgtgaacg agacataagt gttaagaaga3480cataacaatt ataatggaag aagtttgtct ccatttatat attatatatt acccacttat3540gtattatatt aggatgttaa ggagacataa caattataaa gagagaagtt tgtatccatt3600tatatattat atactaccca tttatatatt atacttatcc acttatttaa tgtctttata3660aggtttgatc catgatattt ctaatatttt agttgatatg tatatgaaaa ggtactattt3720gaactctctt actctgtata aaggttggat catccttaaa gtgggtctat ttaattttat3780tgcttcttac agataaaaaa aaaattatga gttggtttga taaaatattg aaggatttaa3840aataataata aataataaat aacatataat atatgtatat aaatttatta taatataaca3900tttatctata aaaaagtaaa tattgtcata aatctataca atcgtttagc cttgctggaa3960cgaatctcaa ttatttaaac gagagtaaac atatttgact ttttggttat ttaacaaatt4020attatttaac actatatgaa attttttttt tttatcagca aagaaataaa attaaattaa4080gaaggacaat ggtgtgtccc aatccttata caaccaactt ccacaagaaa gtcaagtcag4140agacaacaaa aaaacaagca aaggaaattt tttaatttga gttgtcttgt ttgctgcata4200atttatgcag taaaacacta cacataaccc ttttagcagt agagcaatgg ttgaccgtgt4260gcttagcttc ttttatttta tttttttatc agcaaagaat aaataaaata aaatgagaca4320cttcagggat gtttcaaccc ttatacaaaa ccccaaaaac aagtttccta gcaccctacc4380aactaa 4386<210>187<211>456<212>PRT<213>Artificial Sequence<220>
<223>Apo27<400>187
Met Ala Asp Thr Ala Arg Gly Thr His His Asp Ile Ile Gly Arg Asp1 5 10 15Gln Tyr Pro Met Met Gly Arg Asp Arg Asp Gln Tyr Gln Met Ser Gly20 25 30Arg Gly Ser Asp Tyr Ser Lys Ser Arg Gln Ile Ala Lys Ala Ala Thr35 40 45Ala Val Thr Ala Gly Gly Ser Leu Leu Val Leu Ser Ser Leu Thr Leu50 55 60Val Gly Thr Val Ile Ala Leu Thr Val Ala Thr Pro Leu Leu Val Ile65 70 75 80Phe Ser Pro Ile Leu Val Pro Ala Leu Ile Thr Val Ala Leu Leu Ile85 90 95Thr Gly Phe Leu Ser Ser Gly Gly Phe Gly Ile Ala Ala Ile Thr Val100 105 110Phe Ser Trp Ile Tyr Lys Tyr Ala Thr Gly Glu His Pro Gln Gly Ser115 120 125Asp Lys Leu Asp Ser Ala Arg Met Lys Leu Gly Ser Lys Ala Gln Asp130 135 140Leu Lys Asp Arg Ala Gln Tyr Tyr Gly Gln Gln His Thr Gly Gly Glu145 150 155 160His Asp Arg Asp Arg Thr Arg Gly Gly Gln His Thr Thr Met Ala Glu165 170 175Ile Thr Arg Ile Pro Leu Tyr Lys Gly Lys Ser Leu Arg Lys Ala Leu180 185 190Lys Glu His Gly Leu Leu Glu Asp Phe Leu Gln Lys Gln Gln Tyr Gly195 200 205Ile Ser Ser Lys Phe Asp Glu Pro Pro Gln Ser Pro Trp Asp Arg Val210 215 220Lys Asp Leu Ala Thr Val Tyr Val Asp Val Leu Lys Asp Ser Gly Arg225 230 235 240
Asp Tyr Val Ser Gln Phe Glu Gly Ser Ala Leu Gly Lys Gln Leu Asn245 250 255Leu Lys Leu Leu Asp Asn Trp Asp Ser Val Thr Ser Thr Phe Ser Lys260 265 270Leu Arg Glu Gln Leu Gly Pro Val Thr Gln Glu Phe Trp Asp Asn Leu275 280 285Glu Lys Glu Thr Glu Gly Leu Arg Gln Glu Met Ser Lys Asp Leu Glu290 295 300Glu Val Lys Ala Lys Val Gln Pro Tyr Leu Asp Asp Phe Gln Lys Lys305 310 315 320Trp Gln Glu Glu Met Glu Leu Tyr Arg Gln Lys Val Glu Pro Leu Arg325 330 335Ala Glu Leu Gln Glu Gly Ala Arg Gln Lys Leu His Glu Leu Gln Glu340 345 350Lys Leu Ser Pro Leu Gly Glu Glu Met Arg Asp Arg Ala Arg Ala His355 360 365Val Asp Ala Leu Arg Thr His Leu Ala Pro Tyr Ser Asp Glu Leu Arg370 375 380Gln Arg Leu Ala Ala Arg Leu Glu Ala Leu Lys Glu Asn Gly Gly Ala385 390 395 400Arg Leu Ala Glu Tyr His Ala Lys Ala Thr Glu His Leu Ser Thr Leu405 410 415Ser Glu Lys Ala Lys Pro Ala Leu Glu Asp Leu Arg Gln Gly Leu Leu420 425 430Pro Val Leu Glu Ser Phe Lys Val Ser Phe Leu Ser Ala Leu Glu Glu435 440 445Tyr Thr Lys Lys Leu Asn Thr Gln450 455<210>188
<211>39<212>DNA<213>Artificial Sequence<220>
<223>forward primer 1200<400>188gcagcactcg agcaagttcc ggcatttctg gcagcaaga 39<210>189<211>1611<212>DNA<213>Artificial Sequence<220>
<223>Apo27M<400>189atggcggata cagctagagg aacccatcac gatatcatcg gcagagacca gtacccgatg 60atgggccgag accgagacca gtaccagatg tccggacgag gatctgacta ctccaagtct 120aggcagattg ctaaagctgc aactgctgtc acagctggtg gttccctcct tgttctctcc 180agccttaccc ttgttggaac tgtcatagct ttgactgttg caacacctct gctcgttatc 240ttcagcccaa tccttgtccc ggctctcatc acagttgcac tcctcatcac cggttttctt 300tcctctggag ggtttggcat tgccgctata accgttttct cttggattta caagtaagca 360cacatttatc atcttacttc ataattttgt gcaatatgtg catgcatgtg ttgagccagt 420agctttggat caattttttt ggtagaataa caaatgtaac aataagaaat tgcaaattct 480agggaacatt tggttaacta aatacgaaat ttgacctagc tagcttgaat gtgtctgtgt 540atatcatcta tataggtaaa atgcttggta tgatacctat tgattgtgaa taggtacgca 600acgggagagc acccacaggg atcagacaag ttggacagtg caaggatgaa gttgggaagc 660aaagctcagg atctgaaaga cagagctcag tactacggac agcaacatac tggtggggaa 720catgaccgtg accgtactcg tggtggccag cacactacca tggctgagat cacccgcatt 780cctctctaca aaggtaagtc tctccgtaag gcgctgaagg aacatggact tctagaagac 840ttcttgcaga aacaacagta tggcatctcg agcaagttcg atgaaccccc ccagagcccc 900tgggatcgag tgaaggacct ggccactgtg tacgtggatg tgctcaaaga cagcggcaga 960gactatgtgt cccagtttga aggctccgcc ttgggaaaac agctaaacct aaagctcctt1020gacaactggg acagcgtgac ctccaccttc agcaagctgc gcgaacagct cggccctgtg1080acccaggagt tctgggataa cctggaaaag gagacagagg gcctgaggca ggagatgagc1140aaggatctgg aggaggtgaa ggccaaggtg cagccctacc tggacgactt ccagaagaag1200
tggcaggagg agatggagct ctaccgccag aaggtggagc cgctgcgcgc agagctccaa1260gagggcgcgc gccagaagct gcacgagctg caagagaagc tgagcccact gggcgaggag1320atgcgcgacc gcgcgcgcgc ccatgtggac gcgctgcgca cgcatctggc cccctacagc1380gacgagctgc gccagtgctt ggccgcgcgc cttgaggctc tcaaggagaa cggcggcgcc1440agactggccg agtaccacgc caaggccacc gagcatctga gcacgctcag cgagaaggcc1500aagcccgcgc tagaggacct ccgccaaggc ctgctgcccg tgctggagag cttcaaggtc1560agcttcctga gcgctctgga ggagtacact aagaagctca acacccagtg a 1611<210>190<211>456<212>PRT<213>Artificial Sequence<220>
<223>Apo27M<400>190Met Ala Asp Thr Ala Arg Gly Thr His His Asp Ile Ile Gly Arg Asp1 5 10 15Gln Tyr Pro Met Met Gly Arg Asp Arg Asp Gln Tyr Gln Met Ser Gly20 25 30Arg Gly Ser Asp Tyr Ser Lys Ser Arg Gln Ile Ala Lys Ala Ala Thr35 40 45Ala Val Thr Ala Gly Gly Ser Leu Leu Val Leu Ser Ser Leu Thr Leu50 55 60Val Gly Thr Val Ile Ala Leu Thr Val Ala Thr Pro Leu Leu Val Ile65 70 75 80Phe Ser Pro Ile Leu Val Pro Ala Leu Ile Thr Val Ala Leu Leu Ile85 90 95Thr Gly Phe Leu Ser Ser Gly Gly Phe Gly Ile Ala Ala Ile Thr Val100 105 110Phe Ser Trp Ile Tyr Lys Tyr Ala Thr Gly Glu His Pro Gln Gly Ser115 120 125Asp Lys Leu Asp Ser Ala Arg Met Lys Leu Gly Ser Lys Ala Gln Asp
130 135 140Leu Lys Asp Arg Ala Gln Tyr Tyr Gly Gln Gln His Thr Gly Gly Glu145 150 155 160His Asp Arg Asp Arg Thr Arg Gly Gly Gln His Thr Thr Met Ala Glu165 170 175Ile Thr Arg Ile Pro Leu Tyr Lys Gly Lys Ser Leu Arg Lys Ala Leu180 185 190Lys Glu His Gly Leu Leu Glu Asp Phe Leu Gln Lys Gln Gln Tyr Gly195 200 205Ile Ser Ser Lys Phe Asp Glu Pro Pro Gln Ser Pro Trp Asp Arg Val210 215 220Lys Asp Leu Ala Thr Val Tyr Val Asp Val Leu Lys Asp Ser Gly Arg225 230 235 240Asp Tyr Val Ser Gln Phe Glu Gly Ser Ala Leu Gly Lys Gln Leu Asn245 250 255Leu Lys Leu Leu Asp Asn Trp Asp Ser Val Thr Ser Thr Phe Ser Lys260 265 270Leu Arg Glu Gln Leu Gly Pro Val Thr Gln Glu Phe Trp Asp Asn Leu275 280 285Glu Lys Glu Thr Glu Gly Leu Arg Gln Glu Met Ser Lys Asp Leu Glu290 295 300Glu Val Lys Ala Lys Val Gln Pro Tyr Leu Asp Asp Phe Gln Lys Lys305 310 315 320Trp Gln Glu Glu Met Glu Leu Tyr Arg Gln Lys Val Glu Pro Leu Arg325 330 335Ala Glu Leu Gln Glu Gly Ala Arg Gln Lys Leu His Glu Leu Gln Glu340 345 350Lys Leu Ser Pro Leu Gly Glu Glu Met Arg Asp Arg Ala Arg Ala His355 360 365
Val Asp Ala Leu Arg Thr His Leu Ala Pro Tyr Ser Asp Glu Leu Arg370 375 380Gln Cys Leu Ala Ala Arg Leu Glu Ala Leu Lys Glu Asn Gly Gly Ala385 390 395 400Arg Leu Ala Glu Tyr His Ala Lys Ala Thr Glu His Leu Ser Thr Leu405 410 415Ser Glu Lys Ala Lys Pro Ala Leu Glu Asp Leu Arg Gln Gly Leu Leu420 425 430Pro Val Leu Glu Ser Phe Lys Val Ser Phe Leu Ser Ala Leu Glu Glu435 440 445Tyr Thr Lys Lys Leu Asn Thr Gln450 455<210>191<211>39<212>DNA<213>Artificial Sequence<220>
<223>forward primer 1202<400>191gcagcactcg agcaagttcg atgaaccccc ccagagccc 39<210>192<211>25<212>DNA<213>Artificial Sequence<220>
<223>forward primer 1225<400>192cgccagtgct tggccgcgcg ccttg 25<210>193<211>4404<212>DNA<213>Artificial Sequence<220>
<223>Apo28<400>193gaattcattg tactcccagt atcattatag tgaaagtttt ggctctctcg ccggtggttt60
tttacctcta tttaaagggg ttttccacct aaaaattctg gtatcattct cactttactt120gttactttaa tttctcataa tctttggttg aaattatcac gcttccgcac acgatatccc180tacaaattta ttatttgtta aacattttca aaccgcataa aattttatga agtcccgtct240atctttaatg tagtctaaca ttttcatatt gaaatatata atttacttaa ttttagcgtt300ggtagaaagc ataaagattt attcttattc ttcttcatat aaatgtttaa tatacaatat360aaacaaattc tttaccttaa gaaggatttc ccattttata ttttaaaaat atatttatca420aatatttttc aaccacgtaa atctcataat aataagttgt ttcaaaagta ataaaattta480actccataat ttttttattc gactgatctt aaagcaacac ccagtgacac aactagccat540ttttttcttt gaataaaaaa atccaattat cattgtattt tttttataca atgaaaattt600caccaaacaa tcatttgtgg tatttctgaa gcaagtcatg ttatgcaaaa ttctataatt660cccatttgac actacggaag taactgaaga tctgctttta catgcgagac acatcttcta720aagtaatttt aataatagtt actatattca agatttcata tatcaaatac tcaatattac780ttctaaaaaa ttaattagat ataattaaaa tattactttt ttaattttaa gtttaattgt840tgaatttgtg actattgatt tattattcta ctatgtttaa attgttttat agatagttta900aagtaaatat aagtaatgta gtagagtgtt agagtgttac cctaaaccat aaactataac960atttatggtg gactaatttt catatatttc ttattgcttt taccttttct tggtatgtaa1020gtccgtaact agaattacag tgggttgcca tgacactctg tggtcttttg gttcatgcat1080gggtcttgcg caagaaaaag acaaagaaca aagaaaaaag acaaaacaga gagacaaaac1140gcaatcacac aaccaactca aattagtcac tggctgatca agatcgccgc gtccatgtat1200gtctaaatgc catgcaaagc aacacgtgct taacatgcac tttaaatggc tcacccatct1260caacccacac acaaacacat tgcctttttc ttcatcatca ccacaaccac ctgtatatat1320tcattctctt ccgccacctc aatttcttca cttcaacaca cgtcaacctg catatgcgtg1380tcatcccatg cccaaatctc catgcatgtt ccaaccacct tctctcttat ataataccta1440taaatacctc taatatcact cacttctttc atcatccatc catccagagt actactactc1500tactactata ataccccaac ccaactcata ttcaatacta ctctactatg gcggatacag1560ctagaggaac ccatcacgat atcatcggca gagaccagta cccgatgatg ggccgagacc1620gagaccagta ccagatgtcc ggacgaggat ctgactactc caagtctagg cagattgcta1680aagctgcaac tgctgtcaca gctggtggtt ccctccttgt tctctccagc cttacccttg1740ttggaactgt catagctttg actgttgcaa cacctctgct cgttatcttc agcccaatcc1800ttgtcccggc tctcatcaca gttgcactcc tcatcaccgg ttttctttcc tctggagggt1860
ttggcattgc cgctataacc gttttctctt ggatttacaa gtaagcacac atttatcatc1920ttacttcata attttgtgca atatgtgcat gcatgtgttg agccagtagc tttggatcaa1980tttttttggt agaataacaa atgtaacaat aagaaattgc aaattctagg gaacatttgg2040ttaactaaat acgaaatttg acctagctag cttgaatgtg tctgtgtata tcatctatat2100aggtaaaatg cttggtatga tacctattga ttgtgaatag gtacgcaacg ggagagcacc2160cacagggatc agacaagttg gacagtgcaa ggatgaagtt gggaagcaaa gctcaggatc2220tgaaagacag agctcagtac tacggacagc aacatactgg tggggaacat gaccgtgacc2280gtactcgtgg tggccagcac actaccatgg ctgagatcac ccgcattcct ctctacaaag2340gtaagtctct ccgtaaggcg ctgaaggaac atggacttct agaagacttc ttgcagaaac2400aacagtatgg catctcgagc aagttccggc atttctggca gcaagatgaa cccccccaga2460gcccctggga tcgagtgaag gacctggcca ctgtgtacgt ggatgtgctc aaagacagcg2520gcagagacta tgtgtcccag tttgaaggct ccgccttggg aaaacagcta aacctaaagc2580tccttgacaa ctgggacagc gtgacctcca ccttcagcaa gctgcgcgaa cagctcggcc2640ctgtgaccca ggagttctgg gataacctgg aaaaggagac agagggcctg aggcaggaga2700tgagcaagga tctggaggag gtgaaggcca aggtgcagcc ctacctggac gacttccaga2760agaagtggca ggaggagatg gagctctacc gccagaaggt ggagccgctg cgcgcagagc2820tccaagaggg cgcgcgccag aagctgcacg agctgcaaga gaagctgagc ccactgggcg2880aggagatgcg cgaccgcgcg cgcgcccatg tggacgcgct gcgcacgcat ctggccccct2940acagcgacga gctgcgccag cgcttggccg cgcgccttga ggctctcaag gagaacggcg3000gcgccagact ggccgagtac cacgccaagg ccaccgagca tctgagcacg ctcagcgaga3060aggccaagcc cgcgctagag gacctccgcc aaggcctgct gcccgtgctg gagagcttca3120aggtcagctt cctgagcgct ctggaggagt acactaagaa gctcaacacc cagtgaaagc3180ttaaataagt atgaactaaa atgcatgtag gtgtaagagc tcatggagag catggaatat3240tgtatccgac catgtaacag tataataact gagctccatc tcacttcttc tatgaataaa3300caaaggatgt tatgatatat taacactcta tctatgcacc ttattgttct atgataaatt3360tcctcttatt attataaatc atctgaatcg tgacggctta tggaatgctt caaatagtac3420aaaaacaaat gtgtactata agactttcta aacaattcta actttagcat tgtgaacgag3480acataagtgt taagaagaca taacaattat aatggaagaa gtttgtctcc atttatatat3540tatatattac ccacttatgt attatattag gatgttaagg agacataaca attataaaga3600
gagaagtttg tatccattta tatattatat actacccatt tatatattat acttatccac3660ttatttaatg tctttataag gtttgatcca tgatatttct aatattttag ttgatatgta3720tatgaaaagg tactatttga actctcttac tctgtataaa ggttggatca tccttaaagt3780gggtctattt aattttattg cttcttacag ataaaaaaaa aattatgagt tggtttgata3840aaatattgaa ggatttaaaa taataataaa taataaataa catataatat atgtatataa3900atttattata atataacatt tatctataaa aaagtaaata ttgtcataaa tctatacaat3960cgtttagcct tgctggaacg aatctcaatt atttaaacga gagtaaacat atttgacttt4020ttggttattt aacaaattat tatttaacac tatatgaaat tttttttttt tatcagcaaa4080gaaataaaat taaattaaga aggacaatgg tgtgtcccaa tccttataca accaacttcc4140acaagaaagt caagtcagag acaacaaaaa aacaagcaaa ggaaattttt taatttgagt4200tgtcttgttt gctgcataat ttatgcagta aaacactaca cataaccctt ttagcagtag4260agcaatggtt gaccgtgtgc ttagcttctt ttattttatt tttttatcag caaagaataa4320ataaaataaa atgagacact tcagggatgt ttcaaccctt atacaaaacc ccaaaaacaa4380gtttcctagc accctaccaa ctaa 4404<210>194<211>462<212>PRT<213>Artificial Sequence<220>
<223>Apo28<400>194Met Ala Asp Thr Ala Arg Gly Thr His His Asp Ile Ile Gly Arg Asp1 5 10 15Gln Tyr Pro Met Met Gly Arg Asp Arg Asp Gln Tyr Gln Met Ser Gly20 25 30Arg Gly Ser Asp Tyr Ser Lys Ser Arg Gln Ile Ala Lys Ala Ala Thr35 40 45Ala Val Thr Ala Gly Gly Ser Leu Leu Val Leu Ser Ser Leu Thr Leu50 55 60Val Gly Thr Val Ile Ala Leu Thr Val Ala Thr Pro Leu Leu Val Ile65 70 75 80
Phe Ser Pro Ile Leu Val Pro Ala Leu Ile Thr Val Ala Leu Leu Ile85 90 95Thr Gly Phe Leu Ser Ser Gly Gly Phe Gly Ile Ala Ala Ile Thr Val100 105 110Phe Ser Trp Ile Tyr Lys Tyr Ala Thr Gly Glu His Pro Gln Gly Ser115 120 125Asp Lys Leu Asp Ser Ala Arg Met Lys Leu Gly Ser Lys Ala Gln Asp130 135 140Leu Lys Asp Arg Ala Gln Tyr Tyr Gly Gln Gln His Thr Gly Gly Glu145 150 155 160His Asp Arg Asp Arg Thr Arg Gly Gly Gln His Thr Thr Met Ala Glu165 170 175Ile Thr Arg Ile Pro Leu Tyr Lys Gly Lys Ser Leu Arg Lys Ala Leu180 185 190Lys Glu His Gly Leu Leu Glu Asp Phe Leu Gln Lys Gln Gln Tyr Gly195 200 205Ile Ser Ser Lys Phe Arg His Phe Trp Gln Gln Asp Glu Pro Pro Gln210 215 220Ser Pro Trp Asp Arg Val Lys Asp Leu Ala Thr Val Tyr Val Asp Val225 230 235 240Leu Lys Asp Ser Gly Arg Asp Tyr Val Ser Gln Phe Glu Gly Ser Ala245 250 255Leu Gly Lys Gln Leu Asn Leu Lys Leu Leu Asp Asn Trp Asp Ser Val260 265 270Thr Ser Thr Phe Ser Lys Leu Arg Glu Gln Leu Gly Pro Val Thr Gln275 280 285Glu Phe Trp Asp Asn Leu Glu Lys Glu Thr Glu Gly Leu Arg Gln Glu290 295 300Met Ser Lys Asp Leu Glu Glu Val Lys Ala Lys Val Gln Pro Tyr Leu305 310 315 320
Asp Asp Phe Gln Lys Lys Trp Gln Glu Glu Met Glu Leu Tyr Arg Gln325 330 335Lys Val Glu Pro Leu Arg Ala Glu Leu Gln Glu Gly Ala Arg Gln Lys340 345 350Leu His Glu Leu Gln Glu Lys Leu Ser Pro Leu Gly Glu Glu Met Arg355 360 365Asp Arg Ala Arg Ala His Val Asp Ala Leu Arg Thr His Leu Ala Pro370 375 380Tyr Ser Asp Glu Leu Arg Gln Arg Leu Ala Ala Arg Leu Glu Ala Leu385 390 395 400Lys Glu Asn Gly Gly Ala Arg Leu Ala Glu Tyr His Ala Lys Ala Thr405 410 415Glu His Leu Ser Thr Leu Ser Glu Lys Ala Lys Pro Ala Leu Glu Asp420 425 430Leu Arg Gln Gly Leu Leu Pro Val Leu Glu Ser Phe Lys Val Ser Phe435 440 445Leu Ser Ala Leu Glu Glu Tyr Thr Lys Lys Leu Asn Thr Gln450 455 460<210>195<211>25<212>DNA<213>Artificial Sequence<220>
<223>forward primer 1205<400>195ccaagcccgc gctagaggac ctccg 25<210>196<211>3585<212>DNA<213>Artificial Sequence<220>
<223>Apo29<400>196gaattcattg tactcccagt atcattatag tgaaagtttt ggctctctcg ccggtggttt60
tttacctcta tttaaagggg ttttccacct aaaaattctg gtatcattct cactttactt120gttactttaa tttctcataa tctttggttg aaattatcac gcttccgcac acgatatccc180tacaaattta ttatttgtta aacattttca aaccgcataa aattttatga agtcccgtct240atctttaatg tagtctaaca ttttcatatt gaaatatata atttacttaa ttttagcgtt300ggtagaaagc ataaagattt attcttattc ttcttcatat aaatgtttaa tatacaatat360aaacaaattc tttaccttaa gaaggatttc ccattttata ttttaaaaat atatttatca420aatatttttc aaccacgtaa atctcataat aataagttgt ttcaaaagta ataaaattta480actccataat ttttttattc gactgatctt aaagcaacac ccagtgacac aactagccat540ttttttcttt gaataaaaaa atccaattat cattgtattt tttttataca atgaaaattt600caccaaacaa tcatttgtgg tatttctgaa gcaagtcatg ttatgcaaaa ttctataatt660cccatttgac actacggaag taactgaaga tctgctttta catgcgagac acatcttcta720aagtaatttt aataatagtt actatattca agatttcata tatcaaatac tcaatattac780ttctaaaaaa ttaattagat ataattaaaa tattactttt ttaattttaa gtttaattgt840tgaatttgtg actattgatt tattattcta ctatgtttaa attgttttat agatagttta900aagtaaatat aagtaatgta gtagagtgtt agagtgttac cctaaaccat aaactataac960atttatggtg gactaatttt catatatttc ttattgcttt taccttttct tggtatgtaa1020gtccgtaact agaattacag tgggttgcca tgacactctg tggtcttttg gttcatgcat1080gggtcttgcg caagaaaaag acaaagaaca aagaaaaaag acaaaacaga gagacaaaac1140gcaatcacac aaccaactca aattagtcac tggctgatca agatcgccgc gtccatgtat1200gtctaaatgc catgcaaagc aacacgtgct taacatgcac tttaaatggc tcacccatct1260caacccacac acaaacacat tgcctttttc ttcatcatca ccacaaccac ctgtatatat1320tcattctctt ccgccacctc aatttcttca cttcaacaca cgtcaacctg catatgcgtg1380tcatcccatg cccaaatctc catgcatgtt ccaaccacct tctctcttat ataataccta1440taaatacctc taatatcact cacttctttc atcatccatc catccagagt actactactc1500tactactata ataccccaac ccaactcata ttcaatacta ctctaccatg aacttcctta1560agtctttccc tttctacgct ttcctttgtt tcggtcaata cttcgttgct gttacgcatg1620ccatggatga acccccccag agcccctggg atcgagtgaa ggacctggcc actgtgtacg1680tggatgtgct caaagacagc ggcagagact atgtgtccca gtttgaaggc tccgccttgg1740gaaaacagct aaacctaaag ctccttgaca actgggacag cgtgacctcc accttcagca1800
agctgcgcga acagctcggc cctgtgaccc aggagttctg ggataacctg gaaaaggaga1860cagagggcct gaggcaggag atgagcaagg atctggagga ggtgaaggcc aaggtgcagc1920cctacctgga cgacttccag aagaagtggc aggaggagat ggagctctac cgccagaagg1980tggagccgct gcgcgcagag ctccaagagg gcgcgcgcca gaagctgcac gagctgcaag2040agaagctgag cccactgggc gaggagatgc gcgaccgcgc gcgcgcccat gtggacgcgc2100tgcgcacgca tctggccccc tacagcgacg agctgcgcca gcgcttggcc gcgcgccttg2160aggctctcaa ggagaacggc ggcgccagac tggccgagta ccacgccaag gccaccgagc2220atctgagcac gctcagcgag aaggccaagc ccgcgctcga ggacctccgc caaggcctgc2280tgcccgtgct ggagagcttc aaggtcagct tcctgagcgc tctcgaggag tacactaaga2340agctcaacac ccagtgaaag cttaaataag tatgaactaa aatgcatgta ggtgtaagag2400ctcatggaga gcatggaata ttgtatccga ccatgtaaca gtataataac tgagctccat2460ctcacttctt ctatgaataa acaaaggatg ttatgatata ttaacactct atctatgcac2520cttattgttc tatgataaat ttcctcttat tattataaat catctgaatc gtgacggctt2580atggaatgct tcaaatagta caaaaacaaa tgtgtactat aagactttct aaacaattct2640aactttagca ttgtgaacga gacataagtg ttaagaagac ataacaatta taatggaaga2700agtttgtctc catttatata ttatatatta cccacttatg tattatatta ggatgttaag2760gagacataac aattataaag agagaagttt gtatccattt atatattata tactacccat2820ttatatatta tacttatcca cttatttaat gtctttataa ggtttgatcc atgatatttc2880taatatttta gttgatatgt atatgaaaag gtactatttg aactctctta ctctgtataa2940aggttggatc atccttaaag tgggtctatt taattttatt gcttcttaca gataaaaaaa3000aaattatgag ttggtttgat aaaatattga aggatttaaa ataataataa ataataaata3060acatataata tatgtatata aatttattat aatataacat ttatctataa aaaagtaaat3120attgtcataa atctatacaa tcgtttagcc ttgctggaac gaatctcaat tatttaaacg3180agagtaaaca tatttgactt tttggttatt taacaaatta ttatttaaca ctatatgaaa3240tttttttttt ttatcagcaa agaaataaaa ttaaattaag aaggacaatg gtgtgtccca3300atccttatac aaccaacttc cacaagaaag tcaagtcaga gacaacaaaa aaacaagcaa3360aggaaatttt ttaatttgag ttgtcttgtt tgctgcataa tttatgcagt aaaacactac3420acataaccct tttagcagta gagcaatggt tgaccgtgtg cttagcttct tttattttat3480ttttttatca gcaaagaata aataaaataa aatgagacac ttcagggatg tttcaaccct3540tatacaaaac cccaaaaaca agtttcctag caccctacca actaa3585
<210>197<211>269<212>PRT<213>Artificial Sequence<220>
<223>Apo29<400>197Met Asn Phe Leu Lys Ser Phe Pro Phe Tyr Ala Phe Leu Cys Phe Gly1 5 10 15Gln Tyr Phe Val Ala Val Thr His Ala Met Asp Glu Pro Pro Gln Ser20 25 30Pro Trp Asp Arg Val Lys Asp Leu Ala Thr Val Tyr Val Asp Val Leu35 40 45Lys Asp Ser Gly Arg Asp Tyr Val Ser Gln Phe Glu Gly Ser Ala Leu50 55 60Gly Lys Gln Leu Asn Leu Lys Leu Leu Asp Asn Trp Asp Ser Val Thr65 70 75 80Ser Thr Phe Ser Lys Leu Arg Glu Gln Leu Gly Pro Val Thr Gln Glu85 90 95Phe Trp Asp Asn Leu Glu Lys Glu Thr Glu Gly Leu Arg Gln Glu Met100 105 110Ser Lys Asp Leu Glu Glu Val Lys Ala Lys Val Gln Pro Tyr Leu Asp115 120 125Asp Phe Gln Lys Lys Trp Gln Glu Glu Met Glu Leu Tyr Arg Gln Lys130 135 140Val Glu Pro Leu Arg Ala Glu Leu Gln Glu Gly Ala Arg Gln Lys Leu145 150 155 160His Glu Leu Gln Glu Lys Leu Ser Pro Leu Gly Glu Glu Met Arg Asp165 170 175Arg Ala Arg Ala His Val Asp Ala Leu Arg Thr His Leu Ala Pro Tyr180 185 190
Ser Asp Glu Leu Arg Gln Arg Leu Ala Ala Arg Leu Glu Ala Leu Lys195 200 205Glu Asn Gly Gly Ala Arg Leu Ala Glu Tyr His Ala Lys Ala Thr Glu210 215 220His Leu Ser Thr Leu Ser Glu Lys Ala Lys Pro Ala Leu Glu Asp Leu225 230 235 240Arg Gln Gly Leu Leu Pro Val Leu Glu Ser Phe Lys Val Ser Phe Leu245 250 255Ser Ala Leu Glu Glu Tyr Thr Lys Lys Leu Asn Thr Gln260 265<210>198<211>3606<212>DNA<213>Artificial Sequence<220>
<223>Apo30<400>198gaattcattg tactcccagt atcattatag tgaaagtttt ggctctctcg ccggtggttt60tttacctcta tttaaagggg ttttccacct aaaaattctg gtatcattct cactttactt120gttactttaa tttctcataa tctttggttg aaattatcac gcttccgcac acgatatccc180tacaaattta ttatttgtta aacattttca aaccgcataa aattttatga agtcccgtct240atctttaatg tagtctaaca ttttcatatt gaaatatata atttacttaa ttttagcgtt300ggtagaaagc ataaagattt attcttattc ttcttcatat aaatgtttaa tatacaatat360aaacaaattc tttaccttaa gaaggatttc ccattttata ttttaaaaat atatttatca420aatatttttc aaccacgtaa atctcataat aataagttgt ttcaaaagta ataaaattta480actccataat ttttttattc gactgatctt aaagcaacac ccagtgacac aactagccat540ttttttcttt gaataaaaaa atccaattat cattgtattt tttttataca atgaaaattt600caccaaacaa tcatttgtgg tatttctgaa gcaagtcatg ttatgcaaaa ttctataatt660cccatttgac actacggaag taactgaaga tctgctttta catgcgagac acatcttcta720aagtaatttt aataatagtt actatattca agatttcata tatcaaatac tcaatattac780ttctaaaaaa ttaattagat ataattaaaa tattactttt ttaattttaa gtttaattgt840tgaatttgtg actattgatt tattattcta ctatgtttaa attgttttat agatagttta900
aagtaaatat aagtaatgta gtagagtgtt agagtgttac cctaaaccat aaactataac960atttatggtg gactaatttt catatatttc ttattgcttt taccttttct tggtatgtaa1020gtccgtaact agaattacag tgggttgcca tgacactctg tggtcttttg gttcatgcat1080gggtcttgcg caagaaaaag acaaagaaca aagaaaaaag acaaaacaga gagacaaaac1140gcaatcacac aaccaactca aattagtcac tggctgatca agatcgccgc gtccatgtat1200gtctaaatgc catgcaaagc aacacgtgct taacatgcac tttaaatggc tcacccatct1260caacccacac acaaacacat tgcctttttc ttcatcatca ccacaaccac ctgtatatat1320tcattctctt ccgccacctc aatttcttca cttcaacaca cgtcaacctg catatgcgtg1380tcatcccatg cccaaatctc catgcatgtt ccaaccacct tctctcttat ataataccta1440taaatacctc taatatcact cacttctttc atcatccatc catccagagt actactactc1500tactactata ataccccaac ccaactcata ttcaatacta ctctaccatg aacttcctta1560agtctttccc tttctacgct ttcctttgtt tcggtcaata cttcgttgct gttacgcatg1620ccatggggcg gcatttctgg cagcaagatg aaccccccca gagcccctgg gatcgagtga1680aggacctggc cactgtgtac gtggatgtgc tcaaagacag cggcagagac tatgtgtccc1740agtttgaagg ctccgccttg ggaaaacagc taaacctaaa gctccttgac aactgggaca1800gcgtgacctc caccttcagc aagctgcgcg aacagctcgg ccctgtgacc caggagttct1860gggataacct ggaaaaggag acagagggcc tgaggcagga gatgagcaag gatctggagg1920aggtgaaggc caaggtgcag ccctacctgg acgacttcca gaagaagtgg caggaggaga1980tggagctcta ccgccagaag gtggagccgc tgcgcgcaga gctccaagag ggcgcgcgcc2040agaagctgca cgagctgcaa gagaagctga gcccactggg cgaggagatg cgcgaccgcg2100cgcgcgccca tgtggacgcg ctgcgcacgc atctggcccc ctacagcgac gagctgcgcc2160agcgcttggc cgcgcgcctt gaggctctca aggagaacgg cggcgccaga ctggccgagt2220accacgccaa ggccaccgag catctgagca cgctcagcga gaaggccaag cccgcgctcg2280aggacctccg ccaaggcctg ctgcccgtgc tggagagctt caaggtcagc ttcctgagcg2340ctctcgagga gtacactaag aagctcaaca cccagtgaaa gcttaaataa gtatgaacta2400aaatgcatgt aggtgtaaga gctcatggag agcatggaat attgtatccg accatgtaac2460agtataataa ctgagctcca tctcacttct tctatgaata aacaaaggat gttatgatat2520attaacactc tatctatgca ccttattgtt ctatgataaa tttcctctta ttattataaa2580tcatctgaat cgtgacggct tatggaatgc ttcaaatagt acaaaaacaa atgtgtacta2640
taagactttc taaacaattc taactttagc attgtgaacg agacataagt gttaagaaga2700cataacaatt ataatggaag aagtttgtct ccatttatat attatatatt acccacttat2760gtattatatt aggatgttaa ggagacataa caattataaa gagagaagtt tgtatccatt2820tatatattat atactaccca tttatatatt atacttatcc acttatttaa tgtctttata2880aggtttgatc catgatattt ctaatatttt agttgatatg tatatgaaaa ggtactattt2940gaactctctt actctgtata aaggttggat catccttaaa gtgggtctat ttaattttat3000tgcttcttac agataaaaaa aaaattatga gttggtttga taaaatattg aaggatttaa3060aataataata aataataaat aacatataat atatgtatat aaatttatta taatataaca3120tttatctata aaaaagtaaa tattgtcata aatctataca atcgtttagc cttgctggaa3180cgaatctcaa ttatttaaac gagagtaaac atatttgact ttttggttat ttaacaaatt3240attatttaac actatatgaa attttttttt tttatcagca aagaaataaa attaaattaa3300gaaggacaat ggtgtgtccc aatccttata caaccaactt ccacaagaaa gtcaagtcag3360agacaacaaa aaaacaagca aaggaaattt tttaatttga gttgtcttgt ttgctgcata3420atttatgcag taaaacacta cacataaccc ttttagcagt agagcaatgg ttgaccgtgt3480gcttagcttc ttttatttta tttttttatc agcaaagaat aaataaaata aaatgagaca3540cttcagggat gtttcaaccc ttatacaaaa ccccaaaaac aagtttccta gcaccctacc3600aactaa 3606<210>199<211>276<212>PRT<213>Artificial Sequence<220>
<223>Apo30<400>199Met Asn Phe Leu Lys Ser Phe Pro Phe Tyr Ala Phe Leu Cys Phe Gly1 5 10 15Gln Tyr Phe Val Ala Val Thr His Ala Met Gly Arg His Phe Trp Gln20 25 30Gln Asp Glu Pro Pro Gln Ser Pro Trp Asp Arg Val Lys Asp Leu Ala35 40 45Thr Val Tyr Val Asp Val Leu Lys Asp Ser Gly Arg Asp Tyr Val Ser50 55 60
Gln Phe Glu Gly Ser Ala Leu Gly Lys Gln Leu Asn Leu Lys Leu Leu65 70 75 80Asp Asn Trp Asp Ser Val Thr Ser Thr Phe Ser Lys Leu Arg Glu Gln85 90 95Leu Gly Pro Val Thr Gln Glu Phe Trp Asp Asn Leu Glu Lys Glu Thr100 105 110Glu Gly Leu Arg Gln Glu Met Ser Lys Asp Leu Glu Glu Val Lys Ala115 120 125Lys Val Gln Pro Tyr Leu Asp Asp Phe Gln Lys Lys Trp Gln Glu Glu130 135 140Met Glu Leu Tyr Arg Gln Lys Val Glu Pro Leu Arg Ala Glu Leu Gln145 150 155 160Glu Gly Ala Arg Gln Lys Leu His Glu Leu Gln Glu Lys Leu Ser Pro165 170 175Leu Gly Glu Glu Met Arg Asp Arg Ala Arg Ala His Val Asp Ala Leu180 185 190Arg Thr His Leu Ala Pro Tyr Ser Asp Glu Leu Arg Gln Arg Leu Ala195 200 205Ala Arg Leu Glu Ala Leu Lys Glu Asn Gly Gly Ala Arg Leu Ala Glu210 215 220Tyr His Ala Lys Ala Thr Glu His Leu Ser Thr Leu Ser Glu Lys Ala225 230 235 240Lys Pro Ala Leu Glu Asp Leu Arg Gln Gly Leu Leu Pro Val Leu Glu245 250 255Ser Phe Lys Val Ser Phe Leu Ser Ala Leu Glu Glu Tyr Thr Lys Lys260 265 270Leu Asn Thr Gln275<210>200
<211>4332<212>DNA<213>Artificial Sequence<220>
<223>Apo31<400>200gaattcattg tactcccagt atcattatag tgaaagtttt ggctctctcg ccggtggttt60tttacctcta tttaaagggg ttttccacct aaaaattctg gtatcattct cactttactt120gttactttaa tttctcataa tctttggttg aaattatcac gcttccgcac acgatatccc180tacaaattta ttatttgtta aacattttca aaccgcataa aattttatga agtcccgtct240atctttaatg tagtctaaca ttttcatatt gaaatatata atttacttaa ttttagcgtt300ggtagaaagc ataaagattt attcttattc ttcttcatat aaatgtttaa tatacaatat360aaacaaattc tttaccttaa gaaggatttc ccattttata ttttaaaaat atatttatca420aatatttttc aaccacgtaa atctcataat aataagttgt ttcaaaagta ataaaattta480actccataat ttttttattc gactgatctt aaagcaacac ccagtgacac aactagccat540ttttttcttt gaataaaaaa atccaattat cattgtattt tttttataca atgaaaattt600caccaaacaa tcatttgtgg tatttctgaa gcaagtcatg ttatgcaaaa ttctataatt660cccatttgac actacggaag taactgaaga tctgctttta catgcgagac acatcttcta720aagtaatttt aataatagtt actatattca agatttcata tatcaaatac tcaatattac780ttctaaaaaa ttaattagat ataattaaaa tattactttt ttaattttaa gtttaattgt840tgaatttgtg actattgatt tattattcta ctatgtttaa attgttttat agatagttta900aagtaaatat aagtaatgta gtagagtgtt agagtgttac cctaaaccat aaactataac960atttatggtg gactaatttt catatatttc ttattgcttt taccttttct tggtatgtaa1020gtccgtaact agaattacag tgggttgcca tgacactctg tggtcttttg gttcatgcat1080gggtcttgcg caagaaaaag acaaagaaca aagaaaaaag acaaaacaga gagacaaaac1140gcaatcacac aaccaactca aattagtcac tggctgatca agatcgccgc gtccatgtat1200gtctaaatgc catgcaaagc aacacgtgct taacatgcac tttaaatggc tcacccatct1260caacccacac acaaacacat tgcctttttc ttcatcatca ccacaaccac ctgtatatat1320tcattctctt ccgccacctc aatttcttca cttcaacaca cgtcaacctg catatgcgtg1380tcatcccatg cccaaatctc catgcatgtt ccaaccacct tctctcttat ataataccta1440taaatacctc taatatcact cacttctttc atcatccatc catccagagt actactactc1500tactactata ataccccaac ccaactcata ttcaatacta ctctaccatg aacttcctta1560
agtctttccc tttctacgct ttcctttgtt tcggtcaata cttcgttgct gttacgcatg1620ctgacattgt gatgacacag tctccatcct ccctggctat gtcagtggga cagcgggtca1680ctatgcgctg caagtccagt cagagccttt taaaaagtac caatcaaaag aactatttgg1740cctggtacca gcagaaacca ggacagtctc ctaaacttct ggtatacttt gcatccacta1800gggaatctgg ggtccctgat cgcttcatag gcagtggatc tgggacagat ttcactctta1860ccatcagcag tgtgcaggct gaagacctgg cagattactt ctgtcagcaa cattataaca1920ctcctcccac gttcggtgct gggaccaagc tggagcttaa gcggtctccg aacggtgctt1980ctcatagcgg ttctgcacca ggcactagct ctgcatctgg atctcaggtg cacctgcagc2040agtctggagc tgagctgatg aagcctgggg cctcaatgaa gatatcctgc aaggctactg2100gctacacatt cagtagctac tggatagagt gggtaaagca gaggcctgga catggccttg2160agtggattgg agagatttta cctggcagtg gtagtactac ctacaatgag aagttcaagg2220gcaaggccac attcactgca gatacatcct ccaacacagc ctacatgcaa ctcagcagcc2280tgacatctga ggactctgcc gtctattact gtgcaagatt ggatgttgac tcctggggcc2340aaggcaccac tctcacagtc tcgagcaagt tcgatgaacc cccccagagc ccctgggatc2400gagtgaagga cctggccact gtgtacgtgg atgtgctcaa agacagcggc gagactatg2460tgtcccagtt tgaaggctcc gccttgggaa aacagctaaa cctaaagctc cttgacaact2520gggacagcgt gacctccacc ttcagcaagc tgcgcgaaca gctcggccct gtgacccagg2580agttctggga taacctggaa aaggagacag agggcctgag gcaggagatg agcaaggatc2640tggaggaggt gaaggccaag gtgcagccct acctggacga cttccagaag aagtggcagg2700aggagatgga gctctaccgc cagaaggtgg agccgctgcg cgcagagctc caagagggcg2760cgcgccagaa gctgcacgag ctgcaagaga agctgagccc actgggcgag gagatgcgcg2820accgcgcgcg cgcccatgtg gacgcgctgc gcacgcatct ggccccctac agcgacgagc2880tgcgccagcg cttggccgcg cgccttgagg ctctcaagga gaacggcggc gccagactgg2940ccgagtacca cgccaaggcc accgagcatc tgagcacgct cagcgagaag gccaagcccg3000cgctagagga cctccgccaa ggcctgctgc ccgtgctgga gagcttcaag gtcagcttcc3060tgagcgctct ggaggagtac actaagaagc tcaacaccca gtgaaagctt aaataagtat3120gaactaaaat gcatgtaggt gtaagagctc atggagagca tggaatattg tatccgacca3180tgtaacagta taataactga gctccatctc acttcttcta tgaataaaca aaggatgtta3240tgatatatta acactctatc tatgcacctt attgttctat gataaatttc ctcttattat3300
tataaatcat ctgaatcgtg acggcttatg gaatgcttca aatagtacaa aaacaaatgt3360gtactataag actttctaaa caattctaac tttagcattg tgaacgagac ataagtgtta3420agaagacata acaattataa tggaagaagt ttgtctccat ttatatatta tatattaccc3480acttatgtat tatattagga tgttaaggag acataacaat tataaagaga gaagtttgta3540tccatttata tattatatac tacccattta tatattatac ttatccactt atttaatgtc3600tttataaggt ttgatccatg atatttctaa tattttagtt gatatgtata tgaaaaggta3660ctatttgaac tctcttactc tgtataaagg ttggatcatc cttaaagtgg gtctatttaa3720ttttattgct tcttacagat aaaaaaaaaa ttatgagttg gtttgataaa atattgaagg3780atttaaaata ataataaata ataaataaca tataatatat gtatataaat ttattataat3840ataacattta tctataaaaa agtaaatatt gtcataaatc tatacaatcg tttagccttg3900ctggaacgaa tctcaattat ttaaacgaga gtaaacatat ttgacttttt ggttatttaa3960caaattatta tttaacacta tatgaaattt ttttttttta tcagcaaaga aataaaatta4020aattaagaag gacaatggtg tgtcccaatc cttatacaac caacttccac aagaaagtca4080agtcagagac aacaaaaaaa caagcaaagg aaatttttta atttgagttg tcttgtttgc4140tgcataattt atgcagtaaa acactacaca taaccctttt agcagtagag caatggttga4200ccgtgtgctt agcttctttt attttatttt tttatcagca aagaataaat aaaataaaat4260gagacacttc agggatgttt caacccttat acaaaacccc aaaaacaagt ttcctagcac4320cctaccaact aa4332<210>201<211>518<212>PRT<213>Artificial Sequence<220>
<223>Apo31<400>201Met Asn Phe Leu Lys Ser Phe Pro Phe Tyr Ala Phe Leu Cys Phe Gly1 5 10 15Gln Tyr Phe Val Ala Val Thr His Ala Asp Ile Val Met Thr Gln Ser20 25 30Pro Ser Ser Leu Ala Met Ser Val Gly Gln Arg Val Thr Met Arg Cys35 40 45
Lys Ser Ser Gln Ser Leu Leu Lys Ser Thr Asn Gln Lys Asn Tyr Leu50 55 60Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Val Tyr65 70 75 80Phe Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ile Gly Ser85 90 95Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Val Gln Ala Glu100 105 110Asp Leu Ala Asp Tyr Phe Cys Gln Gln His Tyr Asn Thr Pro Pro Thr115 120 125Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys Arg Ser Pro Asn Gly Ala130 135 140Ser His Ser Gly Ser Ala Pro Gly Thr Ser Ser Ala Ser Gly Ser Gln145 150 155 160Val His Leu Gln Gln Ser Gly Ala Glu Leu Met Lys Pro Gly Ala Ser165 170 175Met Lys Ile Ser Cys Lys Ala Thr Gly Tyr Thr Phe Ser Ser Tyr Trp180 185 190Ile Glu Trp Val Lys Gln Arg Pro Gly His Gly Leu Glu Trp Ile Gly195 200 205Glu Ile Leu Pro Gly Ser Gly Ser Thr Thr Tyr Asn Glu Lys Phe Lys210 215 220Gly Lys Ala Thr Phe Thr Ala Asp Thr Ser Ser Asn Thr Ala Tyr Met225 230 235 240Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys Ala245 250 255Arg Leu Asp Val Asp Ser Trp Gly Gln Gly Thr Thr Leu Thr Val Ser260 265 270Ser Lys Phe Asp Glu Pro Pro Gln Ser Pro Trp Asp Arg Val Lys Asp275 280 285
Leu Ala Thr Val Tyr Val Asp Val Leu Lys Asp Ser Gly Arg Asp Tyr290 295 300Val Ser Gln Phe Glu Gly Ser Ala Leu Gly Lys Gln Leu Asn Leu Lys305 310 315 320Leu Leu Asp Asn Trp Asp Ser Val Thr Ser Thr Phe Ser Lys Leu Arg325 330 335Glu Gln Leu Gly Pro Val Thr Gln Glu Phe Trp Asp Asn Leu Glu Lys340 345 350Glu Thr Glu Gly Leu Arg Gln Glu Met Ser Lys Asp Leu Glu Glu Val355 360 365Lys Ala Lys Val Gln Pro Tyr Leu Asp Asp Phe Gln Lys Lys Trp Gln370 375 380Glu Glu Met Glu Leu Tyr Arg Gln Lys Val Glu Pro Leu Arg Ala Glu385 390 395 400Leu Gln Glu Gly Ala Arg Gln Lys Leu His Glu Leu Gln Glu Lys Leu405 410 415Ser Pro Leu Gly Glu Glu Met Arg Asp Arg Ala Arg Ala His Val Asp420 425 430Ala Leu Arg Thr His Leu Ala Pro Tyr Ser Asp Glu Leu Arg Gln Arg435 440 445Leu Ala Ala Arg Leu Glu Ala Leu Lys Glu Asn Gly Gly Ala Arg Leu450 455 460Ala Glu Tyr His Ala Lys Ala Thr Glu His Leu Ser Thr Leu Ser Glu465 470 475 480Lys Ala Lys Pro Ala Leu Glu Asp Leu Arg Gln Gly Leu Leu Pro Val485 490 495Leu Glu Ser Phe Lys Val Ser Phe Leu Ser Ala Leu Glu Glu Tyr Thr500 505 510Lys Lys Leu Asn Thr Gln515
<210>202<211>4350<212>DNA<213>Artificial Sequence<220>
<223>Apo32<400>202gaattcattg tactcccagt atcattatag tgaaagtttt ggctctctcg ccggtggttt60tttacctcta tttaaagggg ttttccacct aaaaattctg gtatcattct cactttactt120gttactttaa tttctcataa tctttggttg aaattatcac gcttccgcac acgatatccc180tacaaattta ttatttgtta aacattttca aaccgcataa aattttatga agtcccgtct240atctttaatg tagtctaaca ttttcatatt gaaatatata atttacttaa ttttagcgtt300ggtagaaagc ataaagattt attcttattc ttcttcatat aaatgtttaa tatacaatat360aaacaaattc tttaccttaa gaaggatttc ccattttata ttttaaaaat atatttatca420aatatttttc aaccacgtaa atctcataat aataagttgt ttcaaaagta ataaaattta480actccataat ttttttattc gactgatctt aaagcaacac ccagtgacac aactagccat540ttttttcttt gaataaaaaa atccaattat cattgtattt tttttataca atgaaaattt600caccaaacaa tcatttgtgg tatttctgaa gcaagtcatg ttatgcaaaa ttctataatt660cccatttgac actacggaag taactgaaga tctgctttta catgcgagac acatcttcta720aagtaatttt aataatagtt actatattca agatttcata tatcaaatac tcaatattac780ttctaaaaaa ttaattagat ataattaaaa tattactttt ttaattttaa gtttaattgt840tgaatttgtg actattgatt tattattcta ctatgtttaa attgttttat agatagttta900aagtaaatat aagtaatgta gtagagtgtt agagtgttac cctaaaccat aaactataac960atttatggtg gactaatttt catatatttc ttattgcttt taccttttct tggtatgtaa1020gtccgtaact agaattacag tgggttgcca tgacactctg tggtcttttg gttcatgcat1080gggtcttgcg caagaaaaag acaaagaaca aagaaaaaag acaaaacaga gagacaaaac1140gcaatcacac aaccaactca aattagtcac tggctgatca agatcgccgc gtccatgtat1200gtctaaatgc catgcaaagc aacacgtgct taacatgcac tttaaatggc tcacccatct1260caacccacac acaaacacat tgcctttttc ttcatcatca ccacaaccac ctgtatatat1320tcattctctt ccgccacctc aatttcttca cttcaacaca cgtcaacctg catatgcgtg1380tcatcccatg cccaaatctc catgcatgtt ccaaccacct tctctcttat ataataccta1440
taaatacctc taatatcact cacttctttc atcatccatc catccagagt actactactc1500tactactata ataccccaac ccaactcata ttcaatacta ctctaccatg aacttcctta1560agtctttccc tttctacgct ttcctttgtt tcggtcaata cttcgttgct gttacgcatg1620ctgacattgt gatgacacag tctccatcct ccctggctat gtcagtggga cagcgggtca1680ctatgcgctg caagtccagt cagagccttt taaaaagtac caatcaaaag aactatttgg1740cctggtacca gcagaaacca ggacagtctc ctaaacttct ggtatacttt gcatccacta1800gggaatctgg ggtccctgat cgcttcatag gcagtggatc tgggacagat ttcactctta1860ccatcagcag tgtgcaggct gaagacctgg cagattactt ctgtcagcaa cattataaca1920ctcctcccac gttcggtgct gggaccaagc tggagcttaa gcggtctccg aacggtgctt1980ctcatagcgg ttctgcacca ggcactagct ctgcatctgg atctcaggtg cacctgcagc2040agtctggagc tgagctgatg aagcctgggg cctcaatgaa gatatcctgc aaggctactg2100gctacacatt cagtagctac tggatagagt gggtaaagca gaggcctgga catggccttg2160agtggattgg agagatttta cctggcagtg gtagtactac ctacaatgag aagttcaagg2220gcaaggccac attcactgca gatacatcct ccaacacagc ctacatgcaa ctcagcagcc2280tgacatctga ggactctgcc gtctattact gtgcaagatt ggatgttgac tcctggggcc2340aaggcaccac tctcacagtc tcgagcaagt tccggcattt ctggcagcaa gatgaacccc2400cccagagccc ctgggatcga gtgaaggacc tggccactgt gtacgtggat gtgctcaaag2460acagcggcag agactatgtg tcccagtttg aaggctccgc cttgggaaaa cagctaaacc2520taaagctcct tgacaactgg gacagcgtga cctccacctt cagcaagctg cgcgaacagc2580tcggccctgt gacccaggag ttctgggata acctggaaaa ggagacagag ggcctgaggc2640aggagatgag caaggatctg gaggaggtga aggccaaggt gcagccctac ctggacgact2700tccagaagaa gtggcaggag gagatggagc tctaccgcca gaaggtggag ccgctgcgcg2760cagagctcca agagggcgcg cgccagaagc tgcacgagct gcaagagaag ctgagcccac2820tgggcgagga gatgcgcgac cgcgcgcgcg cccatgtgga cgcgctgcgc acgcatctgg2880ccccctacag cgacgagctg cgccagcgct tggccgcgcg ccttgaggct ctcaaggaga2940acggcggcgc cagactggcc gagtaccacg ccaaggccac cgagcatctg agcacgctca3000gcgagaaggc caagcccgcg ctagaggacc tccgccaagg cctgctgccc gtgctggaga3060gcttcaaggt cagcttcctg agcgctctgg aggagtacac taagaagctc aacacccagt3120gaaagcttaa ataagtatga actaaaatgc atgtaggtgt aagagctcat ggagagcatg3180gaatattgta tccgaccatg taacagtata ataactgagc tccatctcac ttcttctatg3240
aataaacaaa ggatgttatg atatattaac actctatcta tgcaccttat tgttctatga3300taaatttcct cttattatta taaatcatct gaatcgtgac ggcttatgga atgcttcaaa3360tagtacaaaa acaaatgtgt actataagac tttctaaaca attctaactt tagcattgtg3420aacgagacat aagtgttaag aagacataac aattataatg gaagaagttt gtctccattt3480atatattata tattacccac ttatgtatta tattaggatg ttaaggagac ataacaatta3540taaagagaga agtttgtatc catttatata ttatatacta cccatttata tattatactt3600atccacttat ttaatgtctt tataaggttt gatccatgat atttctaata ttttagttga3660tatgtatatg aaaaggtact atttgaactc tcttactctg tataaaggtt ggatcatcct3720taaagtgggt ctatttaatt ttattgcttc ttacagataa aaaaaaaatt atgagttggt3780ttgataaaat attgaaggat ttaaaataat aataaataat aaataacata taatatatgt3840atataaattt attataatat aacatttatc tataaaaaag taaatattgt cataaatcta3900tacaatcgtt tagccttgct ggaacgaatc tcaattattt aaacgagagt aaacatattt3960gactttttgg ttatttaaca aattattatt taacactata tgaaattttt tttttttatc4020agcaaagaaa taaaattaaa ttaagaagga caatggtgtg tcccaatcct tatacaacca4080acttccacaa gaaagtcaag tcagagacaa caaaaaaaca agcaaaggaa attttttaat4140ttgagttgtc ttgtttgctg cataatttat gcagtaaaac actacacata acccttttag4200cagtagagca atggttgacc gtgtgcttag cttcttttat tttatttttt tatcagcaaa4260gaataaataa aataaaatga gacacttcag ggatgtttca acccttatac aaaaccccaa4320aaacaagttt cctagcaccc taccaactaa 4350<210>203<211>524<212>PRT<213>Artificial Sequence<220>
<223>Apo32<400>203Met Asn Phe Leu Lys Ser Phe Pro Phe Tyr Ala Phe Leu Cys Phe Gly1 5 10 15Gln Tyr Phe Val Ala Val Thr His Ala Asp Ile Val Met Thr Gln Ser20 25 30Pro Ser Ser Leu Ala Met Ser Val Gly Gln Arg Val Thr Met Arg Cys
35 40 45Lys Ser Ser Gln Ser Leu Leu Lys Ser Thr Asn Gln Lys Asn Tyr Leu50 55 60Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Val Tyr65 70 75 80Phe Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ile Gly Ser85 90 95Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Val Gln Ala Glu100 105 110Asp Leu Ala Asp Tyr Phe Cys Gln Gln His Tyr Asn Thr Pro Pro Thr115 120 125Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys Arg Ser Pro Asn Gly Ala130 135 140Ser His Ser Gly Ser Ala Pro Gly Thr Ser Ser Ala Ser Gly Ser Gln145 150 155 160Val His Leu Gln Gln Ser Gly Ala Glu Leu Met Lys Pro Gly Ala Ser165 170 175Met Lys Ile Ser Cys Lys Ala Thr Gly Tyr Thr Phe Ser Ser Tyr Trp180 185 190Ile Glu Trp Val Lys Gln Arg Pro Gly His Gly Leu Glu Trp Ile Gly195 200 205Glu Ile Leu Pro Gly Ser Gly Ser Thr Thr Tyr Asn Glu Lys Phe Lys210 215 220Gly Lys Ala Thr Phe Thr Ala Asp Thr Ser Ser Asn Thr Ala Tyr Met225 230 235 240Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys Ala245 250 255Arg Leu Asp Val Asp Ser Trp Gly Gln Gly Thr Thr Leu Thr Val Ser260 265 270
Ser Lys Phe Arg His Phe Trp Gln Gln Asp Glu Pro Pro Gln Ser Pro275 280 285Trp Asp Arg Val Lys Asp Leu Ala Thr Val Tyr Val Asp Val Leu Lys290 295 300Asp Ser Gly Arg Asp Tyr Val Ser Gln Phe Glu Gly Ser Ala Leu Gly305 310 315 320Lys Gln Leu Asn Leu Lys Leu Leu Asp Asn Trp Asp Ser Val Thr Ser325 330 335Thr Phe Ser Lys Leu Arg Glu Gln Leu Gly Pro Val Thr Gln Glu Phe340 345 350Trp Asp Asn Leu Glu Lys Glu Thr Glu Gly Leu Arg Gln Glu Met Ser355 360 365Lys Asp Leu Glu Glu Val Lys Ala Lys Val Gln Pro Tyr Leu Asp Asp370 375 380Phe Gln Lys Lys Trp Gln Glu Glu Met Glu Leu Tyr Arg Gln Lys Val385 390 395 400Glu Pro Leu Arg Ala Glu Leu Gln Glu Gly Ala Arg Gln Lys Leu His405 410 415Glu Leu Gln Glu Lys Leu Ser Pro Leu Gly Glu Glu Met Arg Asp Arg420 425 430Ala Arg Ala His Val Asp Ala Leu Arg Thr His Leu Ala Pro Tyr Ser435 440 445Asp Glu Leu Arg Gln Arg Leu Ala Ala Arg Leu Glu Ala Leu Lys Glu450 455 460Asn Gly Gly Ala Arg Leu Ala Glu Tyr His Ala Lys Ala Thr Glu His465 470 475 480Leu Ser Thr Leu Ser Glu Lys Ala Lys Pro Ala Leu Glu Asp Leu Arg485 490 495Gln Gly Leu Leu Pro Val Leu Glu Ser Phe Lys Val Ser Phe Leu Ser500 505 510
Ala Leu Glu Glu Tyr Thr Lys Lys Leu Asn Thr Gln515 520<210>204<211>4335<212>DNA<213>Artificial Sequence<220>
<223>Apo33<400>204gaattcattg tactcccagt atcattatag tgaaagtttt ggctctctcg ccggtggttt60tttacctcta tttaaagggg ttttccacct aaaaattctg gtatcattct cactttactt120gttactttaa tttctcataa tctttggttg aaattatcac gcttccgcac acgatatccc180tacaaattta ttatttgtta aacattttca aaccgcataa aattttatga agtcccgtct240atctttaatg tagtctaaca ttttcatatt gaaatatata atttacttaa ttttagcgtt300ggtagaaagc ataaagattt attcttattc ttcttcatat aaatgtttaa tatacaatat360aaacaaattc tttaccttaa gaaggatttc ccattttata ttttaaaaat atatttatca420aatatttttc aaccacgtaa atctcataat aataagttgt ttcaaaagta ataaaattta480actccataat ttttttattc gactgatctt aaagcaacac ccagtgacac aactagccat540ttttttcttt gaataaaaaa atccaattat cattgtattt tttttataca atgaaaattt600caccaaacaa tcatttgtgg tatttctgaa gcaagtcatg ttatgcaaaa ttctataatt660cccatttgac actacggaag taactgaaga tctgctttta catgcgagac acatcttcta720aagtaatttt aataatagtt actatattca agatttcata tatcaaatac tcaatattac780ttctaaaaaa ttaattagat ataattaaaa tattactttt ttaattttaa gtttaattgt840tgaatttgtg actattgatt tattattcta ctatgtttaa attgttttat agatagttta900aagtaaatat aagtaatgta gtagagtgtt agagtgttac cctaaaccat aaactataac960atttatggtg gactaatttt catatatttc ttattgcttt taccttttct tggtatgtaa1020gtccgtaact agaattacag tgggttgcca tgacactctg tggtcttttg gttcatgcat1080gggtcttgcg caagaaaaag acaaagaaca aagaaaaaag acaaaacaga gagacaaaac1140gcaatcacac aaccaactca aattagtcac tggctgatca agatcgccgc gtccatgtat1200gtctaaatgc catgcaaagc aacacgtgct taacatgcac tttaaatggc tcacccatct1260caacccacac acaaacacat tgcctttttc ttcatcatca ccacaaccac ctgtatatat1320tcattctctt ccgccacctc aatttcttca cttcaacaca cgtcaacctg catatgcgtg1380
tcatcccatg cccaaatctc catgcatgtt ccaaccacct tctctcttat ataataccta1440taaatacctc taatatcact cacttctttc atcatccatc catccagagt actactactc1500tactactata ataccccaac ccaactcata ttcaatacta ctctaccatg aacttcctta1560agtctttccc tttctacgct ttcctttgtt tcggtcaata cttcgttgct gttacgcatg1620ctgacattgt gatgacacag tctccatcct ccctggctat gtcagtggga cagcgggtca1680ctatgcgctg caagtccagt cagagccttt taaaaagtac caatcaaaag aactatttgg1740cctggtacca gcagaaacca ggacagtctc ctaaacttct ggtatacttt gcatccacta1800gggaatctgg ggtccctgat cgcttcatag gcagtggatc tgggacagat ttcactctta1860ccatcagcag tgtgcaggct gaagacctgg cagattactt ctgtcagcaa cattataaca1920ctcctcccac gttcggtgct gggaccaagc tggagcttaa gcggtctccg aacggtgctt1980ctcatagcgg ttctgcacca ggcactagct ctgcatctgg atctcaggtg cacctgcagc2040agtctggagc tgagctgatg aagcctgggg cctcaatgaa gatatcctgc aaggctactg2100gctacacatt cagtagctac tggatagagt gggtaaagca gaggcctgga catggccttg2160agtggattgg agagatttta cctggcagtg gtagtactac ctacaatgag aagttcaagg2220gcaaggccac attcactgca gatacatcct ccaacacagc ctacatgcaa ctcagcagcc2280tgacatctga ggactctgcc gtctattact gtgcaagatt ggatgttgac tcctggggcc2340aaggcaccac tctcacagtc tcgagcaagt tcatggatga acccccccag agcccctggg2400atcgagtgaa ggacctggcc actgtgtacg tggatgtgct caaagacagc ggcagagact2460atgtgtccca gtttgaaggc tccgccttgg gaaaacagct aaacctaaag ctccttgaca2520actgggacag cgtgacctcc accttcagca agctgcgcga acagctcggc cctgtgaccc2580aggagttctg ggataacctg gaaaaggaga cagagggcct gaggcaggag atgagcaagg2640atctggagga ggtgaaggcc aaggtgcagc cctacctgga cgacttccag aagaagtggc2700aggaggagat ggagctctac cgccagaagg tggagccgct gcgcgcagag ctccaagagg2760gcgcgcgcca gaagctgcac gagctgcaag agaagctgag cccactgggc gaggagatgc2820gcgaccgcgc gcgcgcccat gtggacgcgc tgcgcacgca tctggccccc tacagcgacg2880agctgcgcca gcgcttggcc gcgcgccttg aggctctcaa ggagaacggc ggcgccagac2940tggccgagta ccacgccaag gccaccgagc atctgagcac gctcagcgag aaggccaagc3000ccgcgctaga ggacctccgc caaggcctgc tgcccgtgct ggagagcttc aaggtcagct3060tcctgagcgc tctggaggag tacactaaga agctcaacac ccagtgaaag cttaaataag3120
tatgaactaa aatgcatgta ggtgtaagag ctcatggaga gcatggaata ttgtatccga3180ccatgtaaca gtataataac tgagctccat ctcacttctt ctatgaataa acaaaggatg3240ttatgatata ttaacactct atctatgcac cttattgttc tatgataaat ttcctcttat3300tattataaat catctgaatc gtgacggctt atggaatgct tcaaatagta caaaaacaaa3360tgtgtactat aagactttct aaacaattct aactttagca ttgtgaacga gacataagtg3420ttaagaagac ataacaatta taatggaaga agtttgtctc catttatata ttatatatta3480cccacttatg tattatatta ggatgttaag gagacataac aattataaag agagaagttt3540qtatccattt atatattata tactacccat ttatatatta tacttatcca cttatttaat3600gtctttataa ggtttgatcc atgatatttc taatatttta gttgatatgt atatgaaaag3660gtactatttg aactctctta ctctgtataa aggttggatc atccttaaag tgggtctatt3720taattttatt gcttcttaca gataaaaaaa aaattatgag ttggtttgat aaaatattga3780aggatttaaa ataataataa ataataaata acatataata tatgtatata aatttattat3840aatataacat ttatctataa aaaagtaaat attgtcataa atctatacaa tcgtttagcc3900ttgctggaac gaatctcaat tatttaaacg agagtaaaca tatttgactt tttggttatt3960taacaaatta ttatttaaca ctatatgaaa tttttttttt ttatcagcaa agaaataaaa4020ttaaattaag aaggacaatg gtgtgtccca atccttatac aaccaacttc cacaagaaag4080tcaagtcaga gacaacaaaa aaacaagcaa aggaaatttt ttaatttgag ttgtcttgtt4140tgctgcataa tttatgcagt aaaacactac acataaccct tttagcagta gagcaatggt4200tgaccgtgtg cttagcttct tttattttat ttttttatca gcaaagaata aataaaataa4260aatgagacac ttcagggatg tttcaaccct tatacaaaac cccaaaaaca agtttcctag4320caccctacca actaa 4335<210>205<211>519<212>PRT<213>Artificial Sequence<220>
<223>Apo33<400>205Met Asn Phe Leu Lys Ser Phe Pro Phe Tyr Ala Phe Leu Cys Phe Gly1 5 10 15Gln Tyr Phe Val Ala Val Thr His Ala Asp Ile Val Met Thr Gln Ser20 25 30
Pro Ser Ser Leu Ala Met Ser Val Gly Gln Arg Val Thr Met Arg Cys35 40 45Lys Ser Ser Gln Ser Leu Leu Lys Ser Thr Asn Gln Lys Asn Tyr Leu50 55 60Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Val Tyr65 70 75 80Phe Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ile Gly Ser85 90 95Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Val Gln Ala Glu100 105 110Asp Leu Ala Asp Tyr Phe Cys Gln Gln His Tyr Asn Thr Pro Pro Thr115 120 125Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys Arg Ser Pro Asn Gly Ala130 135 140Ser His Ser Gly Ser Ala Pro Gly Thr Ser Ser Ala Ser Gly Ser Gln145 150 155 160Val His Leu Gln Gln Ser Gly Ala Glu Leu Met Lys Pro Gly Ala Ser165 170 175Met Lys Ile Ser Cys Lys Ala Thr Gly Tyr Thr Phe Ser Ser Tyr Trp180 185 190Ile Glu Trp Val Lys Gln Arg Pro Gly His Gly Leu Glu Trp Ile Gly195 200 205Glu Ile Leu Pro Gly Ser Gly Ser Thr Thr Tyr Asn Glu Lys Phe Lys210 215 220Gly Lys Ala Thr Phe Thr Ala Asp Thr Ser Ser Asn Thr Ala Tyr Met225 230 235 240Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys Ala245 250 255Arg Leu Asp Val Asp Ser Trp Gly Gln Gly Thr Thr Leu Thr Val Ser
260 265 270Ser Lys Phe Met Asp Glu Pro Pro Gln Ser Pro Trp Asp Arg Val Lys275 280 285Asp Leu Ala Thr Val Tyr Val Asp Val Leu Lys Asp Ser Gly Arg Asp290 295 300Tyr Val Ser Gln Phe Glu Gly Ser Ala Leu Gly Lys Gln Leu Asn Leu305 310 315 320Lys Leu Leu Asp Asn Trp Asp Ser Val Thr Ser Thr Phe Ser Lys Leu325 330 335Arg Glu Gln Leu Gly Pro Val Thr Gln Glu Phe Trp Asp Asn Leu Glu340 345 350Lys Glu Thr Glu Gly Leu Arg Gln Glu Met Ser Lys Asp Leu Glu Glu355 360 365Val Lys Ala Lys Val Gln Pro Tyr Leu Asp Asp Phe Gln Lys Lys Trp370 375 380Gln Glu Glu Met Glu Leu Tyr Arg Gln Lys Val Glu Pro Leu Arg Ala385 390 395 400Glu Leu Gln Glu Gly Ala Arg Gln Lys Leu His Glu Leu Gln Glu Lys405 410 415Leu Ser Pro Leu Gly Glu Glu Met Arg Asp Arg Ala Arg Ala His Val420 425 430Asp Ala Leu Arg Thr His Leu Ala Pro Tyr Ser Asp Glu Leu Arg Gln435 440 445Arg Leu Ala Ala Arg Leu Glu Ala Leu Lys Glu Asn Gly Gly Ala Arg450 455 460Leu Ala Glu Tyr His Ala Lys Ala Thr Glu His Leu Ser Thr Leu Ser465 470 475 480Glu Lys Ala Lys Pro Ala Leu Glu Asp Leu Arg Gln Gly Leu Leu Pro485 490 495
Val Leu Glu Ser Phe Lys Val Ser Phe Leu Ser Ala Leu Glu Glu Tyr500 505 510Thr Lys Lys Leu Asn Thr Gln515<210>206<211>4356<212>DNA<213>Artificial Sequence<220>
<223>Apo34<400>206gaattcattg tactcccagt atcattatag tgaaagtttt ggctctctcg ccggtggttt60tttacctcta tttaaagggg ttttccacct aaaaattctg gtatcattct cactttactt120gttactttaa tttctcataa tctttggttg aaattatcac gcttccgcac acgatatccc180tacaaattta ttatttgtta aacattttca aaccgcataa aattttatga agtcccgtct240atctttaatg tagtctaaca ttttcatatt gaaatatata atttacttaa ttttagcgtt300ggtagaaagc ataaagattt attcttattc ttcttcatat aaatgtttaa tatacaatat360aaacaaattc tttaccttaa gaaggatttc ccattttata ttttaaaaat atatttatca420aatatttttc aaccacgtaa atctcataat aataagttgt ttcaaaagta ataaaattta480actccataat ttttttattc gactgatctt aaagcaacac ccagtgacac aactagccat540ttttttcttt gaataaaaaa atccaattat cattgtattt tttttataca atgaaaattt600caccaaacaa tcatttgtgg tatttctgaa gcaagtcatg ttatgcaaaa ttctataatt660cccatttgac actacggaag taactgaaga tctgctttta catgcgagac acatcttcta720aagtaatttt aataatagtt actatattca agatttcata tatcaaatac tcaatattac780ttctaaaaaa ttaattagat ataattaaaa tattactttt ttaattttaa gtttaattgt840tgaatttgtg actattgatt tattattcta ctatgtttaa attgttttat agatagttta900aagtaaatat aagtaatgta gtagagtgtt agagtgttac cctaaaccat aaactataac960atttatggtg gactaatttt catatatttc ttattgcttt taccttttct tggtatgtaa1020gtccgtaact agaattacag tgggttgcca tgacactctg tggtcttttg gttcatgcat1080gggtcttgcg caagaaaaag acaaagaaca aagaaaaaag acaaaacaga gagacaaaac1140gcaatcacac aaccaactca aattagtcac tggctgatca agatcgccgc gtccatgtat1200gtctaaatgc catgcaaagc aacacgtgct taacatgcac tttaaatggc tcacccatct1260
caacccacac acaaacacat tgcctttttc ttcatcatca ccacaaccac ctgtatatat1320tcattctctt ccgccacctc aatttcttca cttcaacaca cgtcaacctg catatgcgtg1380tcatcccatg cccaaatctc catgcatgtt ccaaccacct tctctcttat ataataccta1440taaatacctc taatatcact cacttctttc atcatccatc catccagagt actactactc1500tactactata ataccccaac ccaactcata ttcaatacta ctctaccatg aacttcctta1560agtctttccc tttctacgct ttcctttgtt tcggtcaata cttcgttgct gttacgcatg1620ctgacattgt gatgacacag tctccatcct ccctggctat gtcagtggga cagcgggtca1680ctatgcgctg caagtccagt cagagccttt taaaaagtac caatcaaaag aactatttgg1740cctggtacca gcagaaacca ggacagtctc ctaaacttct ggtatacttt gcatccacta1800gggaatctgg ggtccctgat cgcttcatag gcagtggatc tgggacagat ttcactctta1860ccatcagcag tgtgcaggct gaagacctgg cagattactt ctgtcagcaa cattataaca1920ctcctcccac gttcggtgct gggaccaagc tggagcttaa gcggtctccg aacggtgctt1980ctcatagcgg ttctgcacca ggcactagct ctgcatctgg atctcaggtg cacctgcagc2040agtctggagc tgagctgatg aagcctgggg cctcaatgaa gatatcctgc aaggctactg2100gctacacatt cagtagctac tggatagagt gggtaaagca gaggcctgga catggccttg2160agtggattgg agagatttta cctggcagtg gtagtactac ctacaatgag aagttcaagg2220gcaaggccac attcactgca gatacatcct ccaacacagc ctacatgcaa ctcagcagcc2280tgacatctga ggactctgcc gtctattact gtgcaagatt ggatgttgac tcctggggcc2340aaggcaccac tctcacagtc tcgagcaagt tcatggggcg gcatttctgg cagcaagatg2400aaccccccca gagcccctgg gatcgagtga aggacctggc cactgtgtac gtggatgtgc2460tcaaagacag cggcagagac tatgtgtccc agtttgaagg ctccgccttg ggaaaacagc2520taaacctaaa gctccttgac aactgggaca gcgtgacctc caccttcagc aagctgcgcg2580aacagctcgg ccctgtgacc caggagttct gggataacct ggaaaaggag acagagggcc2640tgaggcagga gatgagcaag gatctggagg aggtgaaggc caaggtgcag ccctacctgg2700acgacttcca gaagaagtgg caggaggaga tggagctcta ccgccagaag gtggagccgc2760tgcgcgcaga gctccaagag ggcgcgcgcc agaagctgca cgagctgcaa gagaagctga2820gcccactggg cgaggagatg cgcgaccgcg cgcgcgccca tgtggacgcg ctgcgcacgc2880atctggcccc ctacagcgac gagctgcgcc agcgcttggc cgcgcgcctt gaggctctca2940aggagaacgg cggcgccaga ctggccgagt accacgccaa ggccaccgag catctgagca3000cgctcagcga gaaggccaag cccgcgctag aggacctccg ccaaggcctg ctgcccgtgc3060
tggagagctt caaggtcagc ttcctgagcg ctctggagga gtacactaag aagctcaaca3120cccagtgaaa gcttaaataa gtatgaacta aaatgcatgt aggtgtaaga gctcatggag3180agcatggaat attgtatccg accatgtaac agtataataa ctgagctcca tctcacttct3240tctatgaata aacaaaggat gttatgatat attaacactc tatctatgca ccttattgtt3300ctatgataaa tttcctctta ttattataaa tcatctgaat cgtgacggct tatggaatgc3360ttcaaatagt acaaaaacaa atgtgtacta taagactttc taaacaattc taactttagc3420attgtgaacg agacataagt gttaagaaga cataacaatt ataatggaag aagtttgtct3480ccatttatat attatatatt acccacttat gtattatatt aggatgttaa ggagacataa3540caattataaa gagagaagtt tgtatccatt tatatattat atactaccca tttatatatt3600atacttatcc acttatttaa tgtctttata aggtttgatc catgatattt ctaatatttt3660agttgatatg tatatgaaaa ggtactattt gaactctctt actctgtata aaggttggat3720catccttaaa gtgggtctat ttaattttat tgcttcttac agataaaaaa aaaattatga3780gttggtttga taaaatattg aaggatttaa aataataata aataataaat aacatataat3840atatgtatat aaatttatta taatataaca tttatctata aaaaagtaaa tattgtcata3900aatctataca atcgtttagc cttgctggaa cgaatctcaa ttatttaaac gagagtaaac3960atatttgact ttttggttat ttaacaaatt attatttaac actatatgaa attttttttt4020tttatcagca aagaaataaa attaaattaa gaaggacaat ggtgtgtccc aatccttata4080caaccaactt ccacaagaaa gtcaagtcag agacaacaaa aaaacaagca aaggaaattt4140tttaatttga gttgtcttgt ttgctgcata atttatgcag taaaacacta cacataaccc4200ttttagcagt agagcaatgg ttgaccgtgt gcttagcttc ttttatttta tttttttatc4260agcaaagaat aaataaaata aaatgagaca cttcagggat gtttcaaccc ttatacaaaa4320ccccaaaaac aagtttccta gcaccctacc aactaa 4356<210>207<211>526<212>PRT<213>Artificial Sequence<220>
<223>Apo34<400>207Met Asn Phe Leu Lys Ser Phe Pro Phe Tyr Ala Phe Leu Cys Phe Gly1 5 10 15
Gln Tyr Phe Val Ala Val Thr His Ala Asp Ile Val Met Thr Gln Ser20 25 30Pro Ser Ser Leu Ala Met Ser Val Gly Gln Arg Val Thr Met Arg Cys35 40 45Lys Ser Ser Gln Ser Leu Leu Lys Ser Thr Asn Gln Lys Asn Tyr Leu50 55 60Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Val Tyr65 70 75 80Phe Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ile Gly Ser85 90 95Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Val Gln Ala Glu100 105 110Asp Leu Ala Asp Tyr Phe Cys Gln Gln His Tyr Asn Thr Pro Pro Thr115 120 125Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys Arg Ser Pro Asn Gly Ala130 135 140Ser His Ser Gly Ser Ala Pro Gly Thr Ser Ser Ala Ser Gly Ser Gln145 150 155 160Val His Leu Gln Gln Ser Gly Ala Glu Leu Met Lys Pro Gly Ala Ser165 170 175Met Lys Ile Ser Cys Lys Ala Thr Gly Tyr Thr Phe Ser Ser Tyr Trp180 185 190Ile Glu Trp Val Lys Gln Arg Pro Gly His Gly Leu Glu Trp Ile Gly195 200 205Glu Ile Leu Pro Gly Ser Gly Ser Thr Thr Tyr Asn Glu Lys Phe Lys210 215 220Gly Lys Ala Thr Phe Thr Ala Asp Thr Ser Ser Asn Thr Ala Tyr Met225 230 235 240Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys Ala245 250 255
Arg Leu Asp Val Asp Ser Trp Gly Gln Gly Thr Thr Leu Thr Val Ser260 265 270Ser Lys Phe Met Gly Arg His Phe Trp Gln Gln Asp Glu Pro Pro Gln275 280 285Ser Pro Trp Asp Arg Val Lys Asp Leu Ala Thr Val Tyr Val Asp Val290 295 300Leu Lys Asp Ser Gly Arg Asp Tyr Val Ser Gln Phe Glu Gly Ser Ala305 310 315 320Leu Gly Lys Gln Leu Asn Leu Lys Leu Leu Asp Asn Trp Asp Ser Val325 330 335Thr Ser Thr Phe Ser Lys Leu Arg Glu Gln Leu Gly Pro Val Thr Gln340 345 350Glu Phe Trp Asp Asn Leu Glu Lys Glu Thr Glu Gly Leu Arg Gln Glu355 360 365Met Ser Lys Asp Leu Glu Glu Val Lys Ala Lys Val Gln Pro Tyr Leu370 375 380Asp Asp Phe Gln Lys Lys Trp Gln Glu Glu Met Glu Leu Tyr Arg Gln385 390 395 400Lys Val Glu Pro Leu Arg Ala Glu Leu Gln Glu Gly Ala Arg Gln Lys405 410 415Leu His Glu Leu Gln Glu Lys Leu Ser Pro Leu Gly Glu Glu Met Arg420 425 430Asp Arg Ala Arg Ala His Val Asp Ala Leu Arg Thr His Leu Ala Pro435 440 445Tyr Ser Asp Glu Leu Arg Gln Arg Leu Ala Ala Arg Leu Glu Ala Leu450 455 460Lys Glu Asn Gly Gly Ala Arg Leu Ala Glu Tyr His Ala Lys Ala Thr465 470 475 480Glu His Leu Ser Thr Leu Ser Glu Lys Ala Lys Pro Ala Leu Glu Asp
485 490 495Leu Arg Gln Gly Leu Leu Pro Val Leu Glu Ser Phe Lys Val Ser Phe500 505 510Leu Ser Ala Leu Glu Glu Tyr Thr Lys Lys Leu Asn Thr Gln515 520 525<210>208<211>4344<212>DNA<213>Artificial Sequence<220>
<223>Apo35<400>208gaattcattg tactcccagt atcattatag tgaaagtttt ggctctctcg ccggtggttt60tttacctcta tttaaagggg ttttccacct aaaaattctg gtatcattct cactttactt120gttactttaa tttctcataa tctttggttg aaattatcac gcttccgcac acgatatccc180tacaaattta ttatttgtta aacattttca aaccgcataa aattttatga agtcccgtct240atctttaatg tagtctaaca ttttcatatt gaaatatata atttacttaa ttttagcgtt300ggtagaaagc ataaagattt attcttattc ttcttcatat aaatgtttaa tatacaatat360aaacaaattc tttaccttaa gaaggatttc ccattttata ttttaaaaat atatttatca420aatatttttc aaccacgtaa atctcataat aataagttgt ttcaaaagta ataaaattta480actccataat ttttttattc gactgatctt aaagcaacac ccagtgacac aactagccat540ttttttcttt gaataaaaaa atccaattat cattgtattt tttttataca atgaaaattt600caccaaacaa tcatttgtgg tatttctgaa gcaagtcatg ttatgcaaaa ttctataatt660cccatttgac actacggaag taactgaaga tctgctttta catgcgagac acatcttcta720aagtaatttt aataatagtt actatattca agatttcata tatcaaatac tcaatattac780ttctaaaaaa ttaattagat ataattaaaa tattactttt ttaattttaa gtttaattgt840tgaatttgtg actattgatt tattattcta ctatgtttaa attgttttat agatagttta900aagtaaatat aagtaatgta gtagagtgtt agagtgttac cctaaaccat aaactataac960atttatggtg gactaatttt catatatttc ttattgcttt taccttttct tggtatgtaa1020gtccgtaact agaattacag tgggttgcca tgacactctg tggtcttttg gttcatgcat1080gggtcttgcg caagaaaaag acaaagaaca aagaaaaaag acaaaacaga gagacaaaac1140gcaatcacac aaccaactca aattagtcac tggctgatca agatcgccgc gtccatgtat1200
gtctaaatgc catgcaaagc aacacgtgct taacatgcac tttaaatggc tcacccatct1260caacccacac acaaacacat tgcctttttc ttcatcatca ccacaaccac ctgtatatat1320tcattctctt ccgccacctc aatttcttca cttcaacaca cgtcaacctg catatgcgtg1380tcatcccatg cccaaatctc catgcatgtt ccaaccacct tctctcttat ataataccta1440taaatacctc taatatcact cacttctttc atcatccatc catccagagt actactactc1500tactactata ataccccaac ccaactcata ttcaatacta ctctaccatg aacttcctta1560agtctttccc tttctacgct ttcctttgtt tcggtcaata cttcgttgct gttacgcatg1620ctgacattgt gatgacacag tctccatcct ccctggctat gtcagtggga cagcgggtca1680ctatgcgctg caagtccagt cagagccttt taaaaagtac caatcaaaag aactatttgg1740cctggtacca gcagaaacca ggacagtctc ctaaacttct ggtatacttt gcatccacta1800gggaatctgg ggtccctgat cgcttcatag gcagtggatc tgggacagat ttcactctta1860ccatcagcag tgtgcaggct gaagacctgg cagattactt ctgtcagcaa cattataaca1920ctcctcccac gttcggtgct gggaccaagc tggagcttaa gcggtctccg aacggtgctt1980ctcatagcgg ttctgcacca ggcactagct ctgcatctgg atctcaggtg cacctgcagc2040agtctggagc tgagctgatg aagcctgggg cctcaatgaa gatatcctgc aaggctactg2100gctacacatt cagtagctac tggatagagt gggtaaagca gaggcctgga catggccttg2160agtggattgg agagatttta cctggcagtg gtagtactac ctacaatgag aagttcaagg2220gcaaggccac attcactgca gatacatcct ccaacacagc ctacatgcaa ctcagcagcc2280tgacatctga ggactctgcc gtctattact gtgcaagatt ggatgttgac tcctggggcc2340aaggcaccac tctcacagtc tcgagcaagt tcgatgaacc cccccagagc ccctgggatc2400gagtgaagga cctggccact gtgtacgtgg atgtgctcaa agacagcggc agagactatg2460tgtcccagtt tgaaggctcc gccttgggaa aacagctaaa cctaaagctc cttgacaact2520gggacagcgt gacctccacc ttcagcaagc tgcgcgaaca gctcggccct gtgacccagg2580agttctggga taacctggaa aaggagacag agggcctgag gcaggagatg agcaaggatc2640tggaggaggt gaaggccaag gtgcagccct acctggacga cttccagaag aagtggcagg2700aggagatgga gctctaccgc cagaaggtgg agccgctgcg cgcagagctc caagagggcg2760cgcgccagaa gctgcacgag ctgcaagaga agctgagccc actgggcgag gagatgcgcg2820accgcgcgcg cgcccatgtg gacgcgctgc gcacgcatct ggccccctac agcgacgagc2880tgcgccagcg cttggccgcg cgccttgagg ctctcaagga gaacggcggc gccagactgg2940
ccgagtacca cgccaaggcc accgagcatc tgagcacgct cagcgagaag gccaagcccg3000cgctagagga cctccgccaa ggcctgctgc ccgtgctgga gagcttcaag gtcagcttcc3060tgagcgctct ggaggagtac actaagaagc tcaacaccca gaaagatgag ctatgaaagc3120ttaaataagt atgaactaaa atgcatgtag gtgtaagagc tcatggagag catggaatat3180tgtatccgac catgtaacag tataataact gagctccatc tcacttcttc tatgaataaa3240caaaggatgt tatgatatat taacactcta tctatgcacc ttattgttct atgataaatt3300tcctcttatt attataaatc atctgaatcg tgacggctta tggaatgctt caaatagtac3360aaaaaeaaat gtgtactata agactttcta aacaattcta actttagcat tgtgaacgag3420acataagtgt taagaagaca taacaattat aatggaagaa gtttgtctcc atttatatat3480tatatattac ccacttatgt attatattag gatgttaagg agacataaca attataaaga3540gagaagtttg tatccattta tatattatat actacccatt tatatattat acttatccac3600ttatttaatg tctttataag gtttgatcca tgatatttct aatattttag ttgatatgta3660tatgaaaagg tactatttga actctcttac tctgtataaa ggttggatca tccttaaagt3720gggtctattt aattttattg cttcttacag ataaaaaaaa aattatgagt tggtttgata3780aaatattgaa ggatttaaaa taataataaa taataaataa catataatat atgtatataa3840atttattata atataacatt tatctataaa aaagtaaata ttgtcataaa tctatacaat3900cgtttagcct tgctggaacg aatctcaatt atttaaacga gagtaaacat atttgacttt3960ttggttattt aacaaattat tatttaacac tatatgaaat tttttttttt tatcagcaaa4020gaaataaaat taaattaaga aggacaatgg tgtgtcccaa tccttataca accaacttcc4080acaagaaagt caagtcagag acaacaaaaa aacaagcaaa ggaaattttt taatttgagt4140tgtcttgttt gctgcataat ttatgcagta aaacactaca cataaccctt ttagcagtag4200agcaatggtt gaccgtgtgc ttagcttctt ttattttatt tttttatcag caaagaataa4260ataaaataaa atgagacact tcagggatgt ttcaaccctt atacaaaacc ccaaaaacaa4320gtttcctagc accctaccaa ctaa 4344<210>209<211>522<212>PRT<213>Artificial Sequence<220>
<223>Apo35<400>209
Met Asn Phe Leu Lys Ser Phe Pro Phe Tyr Ala Phe Leu Cys Phe Gly1 5 10 15Gln Tyr Phe Val Ala Val Thr His Ala Asp Ile Val Met Thr Gln Ser20 25 30Pro Ser Ser Leu Ala Met Ser Val Gly Gln Arg Val Thr Met Arg Cys35 40 45Lys Ser Ser Gln Ser Leu Leu Lys Ser Thr Asn Gln Lys Asn Tyr Leu50 55 60Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Val Tyr65 70 75 80Phe Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ile Gly Ser85 90 95Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Val Gln Ala Glu100 105 110Asp Leu Ala Asp Tyr Phe Cys Gln Gln His Tyr Asn Thr Pro Pro Thr115 120 125Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys Arg Ser Pro Asn Gly Ala130 135 140Ser His Ser Gly Ser Ala Pro Gly Thr Ser Ser Ala Ser Gly Ser Gln145 150 155 160Val His Leu Gln Gln Ser Gly Ala Glu Leu Met Lys Pro Gly Ala Ser165 170 175Met Lys Ile Ser Cys Lys Ala Thr Gly Tyr Thr Phe Ser Ser Tyr Trp180 185 190Ile Glu Trp Val Lys Gln Arg Pro Gly His Gly Leu Glu Trp Ile Gly195 200 205Glu Ile Leu Pro Gly Ser Gly Ser Thr Thr Tyr Asn Glu Lys Phe Lys210 215 220Gly Lys Ala Thr Phe Thr Ala Asp Thr Ser Ser Asn Thr Ala Tyr Met225 230 235 240
Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys Ala245 250 255Arg Leu Asp Val Asp Ser Trp Gly Gln Gly Thr Thr Leu Thr Val Ser260 265 270Ser Lys Phe Asp Glu Pro Pro Gln Ser Pro Trp Asp Arg Val Lys Asp275 280 285Leu Ala Thr Val Tyr Val Asp Val Leu Lys Asp Ser Gly Arg Asp Tyr290 295 300Val Ser Gln Phe Glu Gly Ser Ala Leu Gly Lys Gln Leu Asn Leu Lys305 310 315 320Leu Leu Asp Asn Trp Asp Ser Val Thr Ser Thr Phe Ser Lys Leu Arg325 330 335Glu Gln Leu Gly Pro Val Thr Gln Glu Phe Trp Asp Asn Leu Glu Lys340 345 350Glu Thr Glu Gly Leu Arg Gln Glu Met Ser Lys Asp Leu Glu Glu Val355 360 365Lys Ala Lys Val Gln Pro Tyr Leu Asp Asp Phe Gln Lys Lys Trp Gln370 375 380Glu Glu Met Glu Leu Tyr Arg Gln Lys Val Glu Pro Leu Arg Ala Glu385 390 395 400Leu Gln Glu Gly Ala Arg Gln Lys Leu His Glu Leu Gln Glu Lys Leu405 410 415Ser Pro Leu Gly Glu Glu Met Arg Asp Arg Ala Arg Ala His Val Asp420 425 430Ala Leu Arg Thr His Leu Ala Pro Tyr Ser Asp Glu Leu Arg Gln Arg435 440 445Leu Ala Ala Arg Leu Glu Ala Leu Lys Glu Asn Gly Gly Ala Arg Leu450 455 460Ala Glu Tyr His Ala Lys Ala Thr Glu His Leu Ser Thr Leu Ser Glu465 470 475 480
Lys Ala Lys Pro Ala Leu Glu Asp Leu Arg Gln Gly Leu Leu Pro Val485 490 495Leu Glu Ser Phe Lys Val Ser Phe Leu Ser Ala Leu Glu Glu Tyr Thr500 505 510Lys Lys Leu Asn Thr Gln Lys Asp Glu Leu515 520<210>210<211>41<212>DNA<213>Artificial Sequence<220>
<223>reverse primer 1208<400>210aagctttcat agctcatctt tctgggtgtt gagcttctta g41<210>211<211>4362<212>DNA<213>Artificial Sequence<220>
<223>Apo36<400>211gaattcattg tactcccagt atcattatag tgaaagtttt ggctctctcg ccggtggttt60tttacctcta tttaaagggg ttttccacct aaaaattctg gtatcattct cactttactt120gttactttaa tttctcataa tctttggttg aaattatcac gcttccgcac acgatatccc180tacaaattta ttatttgtta aacattttca aaccgcataa aattttatga agtcccgtct240atctttaatg tagtctaaca ttttcatatt gaaatatata atttacttaa ttttagcgtt300ggtagaaagc ataaagattt attcttattc ttcttcatat aaatgtttaa tatacaatat360aaacaaattc tttaccttaa gaaggatttc ccattttata ttttaaaaat atatttatca420aatatttttc aaccacgtaa atctcataat aataagttgt ttcaaaagta ataaaattta480actccataat ttttttattc gactgatctt aaagcaacac ccagtgacac aactagccat540ttttttcttt gaataaaaaa atccaattat cattgtattt tttttataca atgaaaattt600caccaaacaa tcatttgtgg tatttctgaa gcaagtcatg ttatgcaaaa ttctataatt660cccatttgac actacggaag taactgaaga tctgctttta catgcgagac acatcttcta720
aagtaatttt aataatagtt actatattca agatttcata tatcaaatac tcaatattac780ttctaaaaaa ttaattagat ataattaaaa tattactttt ttaattttaa gtttaattgt840tgaatttgtg actattgatt tattattcta ctatgtttaa attgttttat agatagttta900aagtaaatat aagtaatgta gtagagtgtt agagtgttac cctaaaccat aaactataac960atttatggtg gactaatttt catatatttc ttattgcttt taccttttct tggtatgtaa1020gtccgtaact agaattacag tgggttgcca tgacactctg tggtcttttg gttcatgcat1080gggtcttgcg caagaaaaag acaaagaaca aagaaaaaag acaaaacaga gagacaaaac1140gcaatcacac aaccaactca aattagtcac tggctgatca agatcgccgc gtccatgtat1200gtctaaatgc catgcaaagc aacacgtgct taacatgcac tttaaatggc tcacccatct1260caacccacac acaaacacat tgcctttttc ttcatcatca ccacaaccac ctgtatatat1320tcattctctt ccgccacctc aatttcttca cttcaacaca cgtcaacctg catatgcgtg1380tcatcccatg cccaaatctc catgcatgtt ccaaccacct tctctcttat ataataccta1440taaatacctc taatatcact cacttctttc atcatccatc catccagagt actactactc1500tactactata ataccccaac ccaactcata ttcaatacta ctctaccatg aacttcctta1560agtctttccc tttctacgct ttcctttgtt tcggtcaata cttcgttgct gttacgcatg1620ctgacattgt gatgacacag tctccatcct ccctggctat gtcagtggga cagcgggtca1680ctatgcgctg caagtccagt cagagccttt taaaaagtac caatcaaaag aactatttgg1740cctggtacca gcagaaacca ggacagtctc ctaaacttct ggtatacttt gcatccacta1800gggaatctgg ggtccctgat cgcttcatag gcagtggatc tgggacagat ttcactctta1860ccatcagcag tgtgcaggct gaagacctgg cagattactt ctgtcagcaa cattataaca1920ctcctcccac gttcggtgct gggaccaagc tggagcttaa gcggtctccg aacggtgctt1980ctcatagcgg ttctgcacca ggcactagct ctgcatctgg atctcaggtg cacctgcagc2040agtctggagc tgagctgatg aagcctgggg cctcaatgaa gatatcctgc aaggctactg2100gctacacatt cagtagctac tggatagagt gggtaaagca gaggcctgga catggccttg2160agtggattgg agagatttta cctggcagtg gtagtactac ctacaatgag aagttcaagg2220gcaaggccac attcactgca gatacatcct ccaacacagc ctacatgcaa ctcagcagcc2280tgacatctga ggactctgcc gtctattact gtgcaagatt ggatgttgac tcctggggcc2340aaggcaccac tctcacagtc tcgagcaagt tccggcattt ctggcagcaa gatgaacccc2400cccagagccc ctgggatcga gtgaaggacc tggccactgt gtacgtggat gtgctcaaag2460acagcggcag agactatgtg tcccagtttg aaggctccgc cttgggaaaa cagctaaacc2520
taaagctcct tgacaactgg gacagcgtga cctccacctt cagcaagctg cgcgaacagc2580tcggccctgt gacccaggag ttctgggata acctggaaaa ggagacagag ggcctgaggc2640aggagatgag caaggatctg gaggaggtga aggccaaggt gcagccctac ctggacgact2700tccagaagaa gtggcaggag gagatggagc tctaccgcca gaaggtggag ccgctgcgcg2760cagagctcca agagggcgcg cgccagaagc tgcacgagct gcaagagaag ctgagcccac2820tgggcgagga gatgcgcgac cgcgcgcgcg cccatgtgga cgcgctgcgc acgcatctgg2880ccccctacag cgacgagctg cgccagcgct tggccgcgcg ccttgaggct ctcaaggaga2940acggcggcgc cagactggcc gagtaccacg ccaaggccac cgagcatctg agcacgctca3000gcgagaaggc caagcccgcg ctagaggacc tccgccaagg cctgctgccc gtgctggaga3060gcttcaaggt cagcttcctg agcgctctgg aggagtacac taagaagctc aacacccaga3120aagatgagct atgaaagctt aaataagtat gaactaaaat gcatgtaggt gtaagagctc3180atggagagca tggaatattg tatccgacca tgtaacagta taataactga gctccatctc3240acttcttcta tgaataaaca aaggatgtta tgatatatta acactctatc tatgcacctt3300attgttctat gataaatttc ctcttattat tataaatcat ctgaatcgtg acggcttatg3360gaatgcttca aatagtacaa aaacaaatgt gtactataag actttctaaa caattctaac3420tttagcattg tgaacgagac ataagtgtta agaagacata acaattataa tggaagaagt3480ttgtctccat ttatatatta tatattaccc acttatgtat tatattagga tgttaaggag3540acataacaat tataaagaga gaagtttgta tccatttata tattatatac tacccattta3600tatattatac ttatccactt atttaatgtc tttataaggt ttgatccatg atatttctaa3660tattttagtt gatatgtata tgaaaaggta ctatttgaac tctcttactc tgtataaagg3720ttggatcatc cttaaagtgg gtctatttaa ttttattgct tcttacagat aaaaaaaaaa3780ttatgagttg gtttgataaa atattgaagg atttaaaata ataataaata ataaataaca3840tataatatat gtatataaat ttattataat ataacattta tctataaaaa agtaaatatt3900gtcataaatc tatacaatcg tttagccttg ctggaacgaa tctcaattat ttaaacgaga3960gtaaacatat ttgacttttt ggttatttaa caaattatta tttaacacta tatgaaattt4020ttttttttta tcagcaaaga aataaaatta aattaagaag gacaatggtg tgtcccaatc4080cttatacaac caacttccac aagaaagtca agtcagagac aacaaaaaaa caagcaaagg4140aaatttttta atttgagttg tcttgtttgc tgcataattt atgcagtaaa acactacaca4200taaccctttt agcagtagag caatggttga ccgtgtgctt agcttctttt attttatttt4260
tttatcagca aagaataaat aaaataaaat gagacacttc agggatgttt caacccttat4320acaaaacccc aaaaacaagt ttcctagcac cctaccaact aa 4362<210>212<211>528<212>PRT<213>Artificial Sequence<220>
<223>Apo36<400>212Met Asn Phe Leu Lys Ser Phe Pro Phe Tyr Ala Phe Leu Cys Phe Gly1 5 10 15Gln Tyr Phe Val Ala Val Thr His Ala Asp Ile Val Met Thr Gln Ser20 25 30Pro Ser Ser Leu Ala Met Ser Val Gly Gln Arg Val Thr Met Arg Cys35 40 45Lys Ser Ser Gln Ser Leu Leu Lys Ser Thr Asn Gln Lys Asn Tyr Leu50 55 60Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Val Tyr65 70 75 80Phe Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ile Gly Ser85 90 95Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Val Gln Ala Glu100 105 110Asp Leu Ala Asp Tyr Phe Cys Gln Gln His Tyr Asn Thr Pro Pro Thr115 120 125Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys Arg Ser Pro Asn Gly Ala130 135 140Ser His Ser Gly Ser Ala Pro Gly Thr Ser Ser Ala Ser Gly Ser Gln145 150 155 160Val His Leu Gln Gln Ser Gly Ala Glu Leu Met Lys Pro Gly Ala Ser165 170 175
Met Lys Ile Ser Cys Lys Ala Thr Gly Tyr Thr Phe Ser Ser Tyr Trp180 185 190Ile Glu Trp Val Lys Gln Arg Pro Gly His Gly Leu Glu Trp Ile Gly195 200 205Glu Ile Leu Pro Gly Ser Gly Ser Thr Thr Tyr Asn Glu Lys Phe Lys210 215 220Gly Lys Ala Thr Phe Thr Ala Asp Thr Ser Ser Asn Thr Ala Tyr Met225 230 235 240Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys Ala245 250 255Arg Leu Asp Val Asp Ser Trp Gly Gln Gly Thr Thr Leu Thr Val Ser260 265 270Ser Lys Phe Arg His Phe Trp Gln Gln Asp Glu Pro Pro Gln Ser Pro275 280 285Trp Asp Arg Val Lys Asp Leu Ala Thr Val Tyr Val Asp Val Leu Lys290 295 300Asp Ser Gly Arg Asp Tyr Val Ser Gln Phe Glu Gly Ser Ala Leu Gly305 310 315 320Lys Gln Leu Asn Leu Lys Leu Leu Asp Asn Trp Asp Ser Val Thr Ser325 330 335Thr Phe Ser Lys Leu Arg Glu Gln Leu Gly Pro Val Thr Gln Glu Phe340 345 350Trp Asp Asn Leu Glu Lys Glu Thr Glu Gly Leu Arg Gln Glu Met Ser355 360 365Lys Asp Leu Glu Glu Val Lys Ala Lys Val Gln Pro Tyr Leu Asp Asp370 375 380Phe Gln Lys Lys Trp Gln Glu Glu Met Glu Leu Tyr Arg Gln Lys Val385 390 395 400Glu Pro Leu Arg Ala Glu Leu Gln Glu Gly Ala Arg Gln Lys Leu His405 410 415
Glu Leu Gln Glu Lys Leu Ser Pro Leu Gly Glu Glu Met Arg Asp Arg420 425 430Ala Arg Ala His Val Asp Ala Leu Arg Thr His Leu Ala Pro Tyr Ser435 440 445Asp Glu Leu Arg Gln Arg Leu Ala Ala Arg Leu Glu Ala Leu Lys Glu450 455 460Asn Gly Gly Ala Arg Leu Ala Glu Tyr His Ala Lys Ala Thr Glu His465 470 475 480Leu Ser Thr Leu Ser Glu Lys Ala Lys Pro Ala Leu Glu Asp Leu Arg485 490 495Gln Gly Leu Leu Pro Val Leu Glu Ser Phe Lys Val Ser Phe Leu Ser500 505 510Ala Leu Glu Glu Tyr Thr Lys Lys Leu Asn Thr Gln Lys Asp Glu Leu515 520 525<210>213<211>4347<212>DNA<213>Artificial Sequence<220>
<223>Apo37<400>213gaattcattg tactcccagt atcattatag tgaaagtttt ggctctctcg ccggtggttt60tttacctcta tttaaagggg ttttccacct aaaaattctg gtatcattct cactttactt120gttactttaa tttctcataa tctttggttg aaattatcac gcttccgcac acgatatccc180tacaaattta ttatttgtta aacattttca aaccgcataa aattttatga agtcccgtct240atctttaatg tagtctaaca ttttcatatt gaaatatata atttacttaa ttttagcgtt300ggtagaaagc ataaagattt attcttattc ttcttcatat aaatgtttaa tatacaatat360aaacaaattc tttaccttaa gaaggatttc ccattttata ttttaaaaat atatttatca420aatatttttc aaccacgtaa atctcataat aataagttgt ttcaaaagta ataaaattta480actccataat ttttttattc gactgatctt aaagcaacac ccagtgacac aactagccat540ttttttcttt gaataaaaaa atccaattat cattgtattt tttttataca atgaaaattt600caccaaacaa tcatttgtgg tatttctgaa gcaagtcatg ttatgcaaaa ttctataatt660
cccatttgac actacggaag taactgaaga tctgctttta catgcgagac acatcttcta720aagtaatttt aataatagtt actatattca agatttcata tatcaaatac tcaatattac780ttctaaaaaa ttaattagat ataattaaaa tattactttt ttaattttaa gtttaattgt840tgaatttgtg actattgatt tattattcta ctatgtttaa attgttttat agatagttta900aagtaaatat aagtaatgta gtagagtgtt agagtgttac cctaaaccat aaactataac960atttatggtg gactaatttt catatatttc ttattgcttt taccttttct tggtatgtaa1020gtccgtaact agaattacag tgggttgcca tgacactctg tggtcttttg gttcatgcat1080gggtcttgcg caagaaaaag acaaagaaca aagaaaaaag acaaaacaga gagacaaaac1140gcaatcacac aaccaactca aattagtcac tggctgatca agatcgccgc gtccatgtat1200gtctaaatgc catgcaaagc aacacgtgct taacatgcac tttaaatggc tcacccatct1260caacccacac acaaacacat tgcctttttc ttcatcatca ccacaaccac ctgtatatat1320tcattctctt ccgccacctc aatttcttca cttcaacaca cgtcaacctg catatgcgtg1380tcatcccatg cccaaatctc catgcatgtt ccaaccacct tctctcttat ataataccta1440taaatacctc taatatcact cacttctttc atcatccatc catccagagt actactactc1500tactactata ataccccaac ccaactcata ttcaatacta ctctaccatg aacttcctta1560agtctttccc tttctacgct ttcctttgtt tcggtcaata cttcgttgct gttacgcatg1620ctgacattgt gatgacacag tctccatcct ccctggctat gtcagtggga cagcgggtca1680ctatgcgctg caagtccagt cagagccttt taaaaagtac caatcaaaag aactatttgg1740cctggtacca gcagaaacca ggacagtctc ctaaacttct ggtatacttt gcatccacta1800gggaatctgg ggtccctgat cgcttcatag gcagtggatc tgggacagat ttcactctta1860ccatcagcag tgtgcaggct gaagacctgg cagattactt ctgtcagcaa cattataaca1920ctcctcccac gttcggtgct gggaccaagc tggagcttaa gcggtctccg aacggtgctt1980ctcatagcgg ttctgcacca ggcactagct ctgcatctgg atctcaggtg cacctgcagc2040agtctggagc tgagctgatg aagcctgggg cctcaatgaa gatatcctgc aaggctactg2100gctacacatt cagtagctac tggatagagt gggtaaagca gaggcctgga catggccttg2160agtggattgg agagatttta cctggcagtg gtagtactac ctacaatgag aagttcaagg2220gcaaggccac attcactgca gatacatcct ccaacacagc ctacatgcaa ctcagcagcc2280tgacatctga ggactctgcc gtctattact gtgcaagatt ggatgttgac tcctggggcc2340aaggcaccac tctcacagtc tcgagcaagt tcatggatga acccccccag agcccctggg2400
atcgagtgaa ggacctggcc actgtgtacg tggatgtgct caaagacagc ggcagagact2460atgtgtccca gtttgaaggc tccgccttgg gaaaacagct aaacctaaag ctccttgaca2520actgggacag cgtgacctcc accttcagca agctgcgcga acagctcggc cctgtgaccc2580aggagttctg ggataacctg gaaaaggaga cagagggcct gaggcaggag atgagcaagg2640atctggagga ggtgaaggcc aaggtgcagc cctacctgga cgacttccag aagaagtggc2700aggaggagat ggagctctac cgccagaagg tggagccgct gcgcgcagag ctccaagagg2760gcgcgcgcca gaagctgcac gagctgcaag agaagctgag cccactgggc gaggagatgc2820gcgaccgcgc gcgcgcccat gtggacgcgc tgcgcacgca tctggccccc tacagcgacg2880agctgcgcca gcgcttggcc gcgcgccttg aggctctcaa ggagaacggc ggcgccagac2940tggccgagta ccacgccaag gccaccgagc atctgagcac gctcagcgag aaggccaagc3000ccgcgctaga ggacctccgc caaggcctgc tgcccgtgct ggagagcttc aaggtcagct3060tcctgagcgc tctggaggag tacactaaga agctcaacac ccagaaagat gagctatgaa3120agcttaaata agtatgaact aaaatgcatg taggtgtaag agctcatgga gagcatggaa3180tattgtatcc gaccatgtaa cagtataata actgagctcc atctcacttc ttctatgaat3240aaacaaagga tgttatgata tattaacact ctatctatgc accttattgt tctatgataa3300atttcctctt attattataa atcatctgaa tcgtgacggc ttatggaatg cttcaaatag3360tacaaaaaca aatgtgtact ataagacttt ctaaacaatt ctaactttag cattgtgaac3420gagacataag tgttaagaag acataacaat tataatggaa gaagtttgtc tccatttata3480tattatatat tacccactta tgtattatat taggatgtta aggagacata acaattataa3540agagagaagt ttgtatccat ttatatatta tatactaccc atttatatat tatacttatc3600cacttattta atgtctttat aaggtttgat ccatgatatt tctaatattt tagttgatat3660gtatatgaaa aggtactatt tgaactctct tactctgtat aaaggttgga tcatccttaa3720agtgggtcta tttaatttta ttgcttctta cagataaaaa aaaaattatg agttggtttg3780ataaaatatt gaaggattta aaataataat aaataataaa taacatataa tatatgtata3840taaatttatt ataatataac atttatctat aaaaaagtaa atattgtcat aaatctatac3900aatcgtttag ccttgctgga acgaatctca attatttaaa cgagagtaaa catatttgac3960tttttggtta tttaacaaat tattatttaa cactatatga aatttttttt ttttatcagc4020aaagaaataa aattaaatta agaaggacaa tggtgtgtcc caatccttat acaaccaact4080tccacaagaa agtcaagtca gagacaacaa aaaaacaagc aaaggaaatt ttttaatttg4140agttgtcttg tttgctgcat aatttatgca gtaaaacact acacataacc cttttagcag4200
tagagcaatg gttgaccgtg tgcttagctt cttttatttt atttttttat cagcaaagaa4260taaataaaat aaaatgagac acttcaggga tgtttcaacc cttatacaaa accccaaaaa4320caagtttcct agcaccctac caactaa4347<210>214<211>523<212>PRT<213>Artificial Sequence<220>
<223>Apo37<400>214Met Asn Phe Leu Lys Ser Phe Pro Phe Tyr Ala Phe Leu Cys Phe Gly1 5 10 15Gln Tyr Phe Val Ala Val Thr His Ala Asp Ile Val Met Thr Gln Ser20 25 30Pro Ser Ser Leu Ala Met Ser Val Gly Gln Arg Val Thr Met Arg Cys35 40 45Lys Ser Ser Gln Ser Leu Leu Lys Ser Thr Asn Gln Lys Asn Tyr Leu50 55 60Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Val Tyr65 70 75 80Phe Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ile Gly Ser85 90 95Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Val Gln Ala Glu100 105 110Asp Leu Ala Asp Tyr Phe Cys Gln Gln His Tyr Asn Thr Pro Pro Thr115 120 125Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys Arg Ser Pro Asn Gly Ala130 135 140Ser His Ser Gly Ser Ala Pro Gly Thr Ser Ser Ala Ser Gly Ser Gln145 150 155 160Val His Leu Gln Gln Ser Gly Ala Glu Leu Met Lys Pro Gly Ala Ser
165 170 175Met Lys Ile Ser Cys Lys Ala Thr Gly Tyr Thr Phe Ser Ser Tyr Trp180 185 190Ile Glu Trp Val Lys Gln Arg Pro Gly His Gly Leu Glu Trp Ile Gly195 200 205Glu Ile Leu Pro Gly Ser Gly Ser Thr Thr Tyr Asn Glu Lys Phe Lys210 215 220Gly Lys Ala Thr Phe Thr Ala Asp Thr Ser Ser Asn Thr Ala Tyr Met225 230 235 240Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys Ala245 250 255Arg Leu Asp Val Asp Ser Trp Gly Gln Gly Thr Thr Leu Thr Val Ser260 265 270Ser Lys Phe Met Asp Glu Pro Pro Gln Ser Pro Trp Asp Arg Val Lys275 280 285Asp Leu Ala Thr Val Tyr Val Asp Val Leu Lys Asp Ser Gly Arg Asp290 295 300Tyr Val Ser Gln Phe Glu Gly Ser Ala Leu Gly Lys Gln Leu Asn Leu305 310 315 320Lys Leu Leu Asp Asn Trp Asp Ser Val Thr Ser Thr Phe Ser Lys Leu325 330 335Arg Glu Gln Leu Gly Pro Val Thr Gln Glu Phe Trp Asp Asn Leu Glu340 345 350Lys Glu Thr Glu Gly Leu Arg Gln Glu Met Ser Lys Asp Leu Glu Glu355 360 365Val Lys Ala Lys Val Gln Pro Tyr Leu Asp Asp Phe Gln Lys Lys Trp37 0375 380Gln Glu Glu Met Glu Leu Tyr Arg Gln Lys Val Glu Pro Leu Arg Ala385 390 395 400
Glu Leu Gln Glu Gly Ala Arg Gln Lys Leu His Glu Leu Gln Glu Lys405 410 415Leu Ser Pro Leu Gly Glu Glu Met Arg Asp Arg Ala Arg Ala His Val420 425 430Asp Ala Leu Arg Thr His Leu Ala Pro Tyr Ser Asp Glu Leu Arg Gln435 440 445Arg Leu Ala Ala Arg Leu Glu Ala Leu Lys Glu Asn Gly Gly Ala Arg450 455 460Leu Ala Glu Tyr His Ala Lys Ala Thr Glu His Leu Ser Thr Leu Ser465 470 475 480Glu Lys Ala Lys Pro Ala Leu Glu Asp Leu Arg Gln Gly Leu Leu Pro485 490 495Val Leu Glu Ser Phe Lys Val Ser Phe Leu Ser Ala Leu Glu Glu Tyr500 505 510Thr Lys Lys Leu Asn Thr Gln Lys Asp Glu Leu515 520<210>215<211>4368<212>DNA<213>Artificial Sequence<220>
<223>Apo38<400>215gaattcattg tactcccagt atcattatag tgaaagtttt ggctctctcg ccggtggttt60tttacctcta tttaaagggg ttttccacct aaaaattctg gtatcattct cactttactt120gttactttaa tttctcataa tctttggttg aaattatcac gcttccgcac acgatatccc180tacaaattta ttatttgtta aacattttca aaccgcataa aattttatga agtcccgtct240atctttaatg tagtctaaca ttttcatatt gaaatatata atttacttaa ttttagcgtt300ggtagaaagc ataaagattt attcttattc ttcttcatat aaatgtttaa tatacaatat360aaacaaattc tttaccttaa gaaggatttc ccattttata ttttaaaaat atatttatca420aatatttttc aaccacgtaa atctcataat aataagttgt ttcaaaagta ataaaattta480actccataat ttttttattc gactgatctt aaagcaacac ccagtgacac aactagccat540
ttttttcttt gaataaaaaa atccaattat cattgtattt tttttataca atgaaaattt600caccaaacaa tcatttgtgg tatttctgaa gcaagtcatg ttatgcaaaa ttctataatt660cccatttgac actacggaag taactgaaga tctgctttta catgcgagac acatcttcta720aagtaatttt aataatagtt actatattca agatttcata tatcaaatac tcaatattac780ttctaaaaaa ttaattagat ataattaaaa tattactttt ttaattttaa gtttaattgt840tgaatttgtg actattgatt tattattcta ctatgtttaa attgttttat agatagttta900aagtaaatat aagtaatgta gtagagtgtt agagtgttac cctaaaccat aaactataac960atttatggtg gactaatttt catatatttc ttattgcttt taccttttct tggtatgtaa1020gtccgtaact agaattacag tgggttgcca tgacactctg tggtcttttg gttcatgcat1080gggtcttgcg caagaaaaag acaaagaaca aagaaaaaag acaaaacaga gagacaaaac1140gcaatcacac aaccaactca aattagtcac tggctgatca agatcgccgc gtccatgtat1200gtctaaatgc catgcaaagc aacacgtgct taacatgcac tttaaatggc tcacccatct1260caacccacac acaaacacat tgcctttttc ttcatcatca ccacaaccac ctgtatatat1320tcattctctt ccgccacctc aatttcttca cttcaacaca cgtcaacctg catatgcgtg1380tcatcccatg cccaaatctc catgcatgtt ccaaccacct tctctcttat ataataccta1440taaatacctc taatatcact cacttctttc atcatccatc catccagagt actactactc1500tactactata ataccccaac ccaactcata ttcaatacta ctctaccatg aacttcctta1560agtctttccc tttctacgct ttcctttgtt tcggtcaata cttcgttgct gttacgcatg1620ctgacattgt gatgacacag tctccatcct ccctggctat gtcagtggga cagcgggtca1680ctatgcgctg caagtccagt cagagccttt taaaaagtac caatcaaaag aactatttgg1740cctggtacca gcagaaacca ggacagtctc ctaaacttct ggtatacttt gcatccacta1800gggaatctgg ggtccctgat cgcttcatag gcagtggatc tgggacagat ttcactctta1860ccatcagcag tgtgcaggct gaagacctgg cagattactt ctgtcagcaa cattataaca1920ctcctcccac gttcggtgct gggaccaagc tggagcttaa gcggtctccg aacggtgctt1980ctcatagcgg ttctgcacca ggcactagct ctgcatctgg atctcaggtg cacctgcagc2040agtctggagc tgagctgatg aagcctgggg cctcaatgaa gatatcctgc aaggctactg2100gctacacatt cagtagctac tggatagagt gggtaaagca gaggcctgga catggccttg2160agtggattgg agagatttta cctggcagtg gtagtactac ctacaatgag aagttcaagg2220gcaaggccac attcactgca gatacatcct ccaacacagc ctacatgcaa ctcagcagcc2280tgacatctga ggactctgcc gtctattact gtgcaagatt ggatgttgac tcctggggcc2340
aaggcaccac tctcacagtc tcgagcaagt tcatggggcg gcatttctgg cagcaagatg2400aaccccccca gagcccctgg gatcgagtga aggacctggc cactgtgtac gtggatgtgc2460tcaaagacag cggcagagac tatgtgtccc agtttgaagg ctccgccttg ggaaaacagc2520taaacctaaa gctccttgac aactgggaca gcgtgacctc caccttcagc aagctgcgcg2580aacagctcgg ccctgtgacc caggagttct gggataacct ggaaaaggag acagagggcc2640tgaggcagga gatgagcaag gatctggagg aggtgaaggc caaggtgcag ccctacctgg2700acgacttcca gaagaagtgg caggaggaga tggagctcta ccgccagaag gtggagccgc2760tgcgcgcaga gctccaagag ggcgcgcgcc agaagctgca cgagctgcaa gagaagctga2820gcccactggg cgaggagatg cgcgaccgcg cgcgcgccca tgtggacgcg ctgcgcacgc2880atctggcccc ctacagcgac gagctgcgcc agcgcttggc cgcgcgcctt gaggctctca2940aggagaacgg cggcgccaga ctggccgagt accacgccaa ggccaccgag catctgagca3000cgctcagcga gaaggccaag cccgcgctag aggacctccg ccaaggcctg ctgcccgtgc3060tggagagctt caaggtcagc ttcctgagcg ctctggagga gtacactaag aagctcaaca3120cccagaaaga tgagctatga aagcttaaat aagtatgaac taaaatgcat gtaggtgtaa3180gagctcatgg agagcatgga atattgtatc cgaccatgta acagtataat aactgagctc3240catctcactt cttctatgaa taaacaaagg atgttatgat atattaacac tctatctatg3300caccttattg ttctatgata aatttcctct tattattata aatcatctga atcgtgacgg3360cttatggaat gcttcaaata gtacaaaaac aaatgtgtac tataagactt tctaaacaat3420tctaacttta gcattgtgaa cgagacataa gtgttaagaa gacataacaa ttataatgga3480agaagtttgt ctccatttat atattatata ttacccactt atgtattata ttaggatgtt3540aaggagacat aacaattata aagagagaag tttgtatcca tttatatatt atatactacc3600catttatata ttatacttat ccacttattt aatgtcttta taaggtttga tccatgatat3660ttctaatatt ttagttgata tgtatatgaa aaggtactat ttgaactctc ttactctgta3720taaaggttgg atcatcctta aagtgggtct atttaatttt attgcttctt acagataaaa3780aaaaaattat gagttggttt gataaaatat tgaaggattt aaaataataa taaataataa3840ataacatata atatatgtat ataaatttat tataatataa catttatcta taaaaaagta3900aatattgtca taaatctata caatcgttta gccttgctgg aacgaatctc aattatttaa3960acgagagtaa acatatttga ctttttggtt atttaacaaa ttattattta acactatatg4020aaattttttt tttttatcag caaagaaata aaattaaatt aagaaggaca atggtgtgtc4080
ccaatcctta tacaaccaac ttccacaaga aagtcaagtc agagacaaca aaaaaacaag4140caaaggaaat tttttaattt gagttgtctt gtttgctgca taatttatgc agtaaaacac4200tacacataac ccttttagca gtagagcaat ggttgaccgt gtgcttagct tcttttattt4260tattttttta tcagcaaaga ataaataaaa taaaatgaga cacttcaggg atgtttcaac4320ccttatacaa aaccccaaaa acaagtttcc tagcacccta ccaactaa 4368<210>216<211>530<212>PRT<213>Artificial Sequence<220>
<223>Apo38<400>216Met Asn Phe Leu Lys Ser Phe Pro Phe Tyr Ala Phe Leu Cys Phe Gly1 5 10 15Gln Tyr Phe Val Ala Val Thr His Ala Asp Ile Val Met Thr Gln Ser20 25 30Pro Ser Ser Leu Ala Met Ser Val Gly Gln Arg Val Thr Met Arg Cys35 40 45Lys Ser Ser Gln Ser Leu Leu Lys Ser Thr Asn Gln Lys Asn Tyr Leu50 55 60Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Val Tyr65 70 75 80Phe Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ile Gly Ser85 90 95Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Val Gln Ala Glu100 105 110Asp Leu Ala Asp Tyr Phe Cys Gln Gln His Tyr Asn Thr Pro Pro Thr115 120 125Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys Arg Ser Pro Asn Gly Ala130 135 140Ser His Ser Gly Ser Ala Pro Gly Thr Ser Ser Ala Ser Gly Ser Gln145 150 155 160
Val His Leu Gln Gln Ser Gly Ala Glu Leu Met Lys Pro Gly Ala Ser165 170 175Met Lys Ile Ser Cys Lys Ala Thr Gly Tyr Thr Phe Ser Ser Tyr Trp180 185 190Ile Glu Trp Val Lys Gln Arg Pro Gly His Gly Leu Glu Trp Ile Gly195 200 205Glu Ile Leu Pro Gly Ser Gly Ser Thr Thr Tyr Asn Glu Lys Phe Lys210 215 220Gly Lys Ala Thr Phe Thr Ala Asp Thr Ser Ser Asn Thr Ala Tyr Met225 230 235 240Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys Ala245 250 255Arg Leu Asp Val Asp Ser Trp Gly Gln Gly Thr Thr Leu Thr Val Ser260 265 270Ser Lys Phe Met Gly Arg His Phe Trp Gln Gln Asp Glu Pro Pro Gln275 280 285Ser Pro Trp Asp Arg Val Lys Asp Leu Ala Thr Val Tyr Val Asp Val290 295 300Leu Lys Asp Ser Gly Arg Asp Tyr Val Ser Gln Phe Glu Gly Ser Ala305 310 315 320Leu Gly Lys Gln Leu Asn Leu Lys Leu Leu Asp Asn Trp Asp Ser Val325 330 335Thr Ser Thr Phe Ser Lys Leu Arg Glu Gln Leu Gly Pro Val Thr Gln340 345 350Glu Phe Trp Asp Asn Leu Glu Lys Glu Thr Glu Gly Leu Arg Gln Glu355 360 365Met Ser Lys Asp Leu Glu Glu Val Lys Ala Lys Val Gln Pro Tyr Leu370 375 380Asp Asp Phe Gln Lys Lys Trp Gln Glu Glu Met Glu Leu Tyr Arg Gln
385 390 395 400Lys Val Glu Pro Leu Arg Ala Glu Leu Gln Glu Gly Ala Arg Gln Lys405 410 415Leu His Glu Leu Gln Glu Lys Leu Ser Pro Leu Gly Glu Glu Met Arg420 425 430Asp Arg Ala Arg Ala His Val Asp Ala Leu Arg Thr His Leu Ala Pro435 440 445Tyr Ser Asp Glu Leu Arg Gln Arg Leu Ala Ala Arg Leu Glu Ala Leu450 455 460Lys Glu Asn Gly Gly Ala Arg Leu Ala Glu Tyr His Ala Lys Ala Thr465 470 475 480Glu His Leu Ser Thr Leu Ser Glu Lys Ala Lys Pro Ala Leu Glu Asp485 490 495Leu Arg Gln Gly Leu Leu Pro Val Leu Glu Ser Phe Lys Val Ser Phe500 505 510Leu Ser Ala Leu Glu Glu Tyr Thr Lys Lys Leu Asn Thr Gln Lys Asp515 520 525Glu Leu530<210>217<211>4446<212>DNA<213>Artificial Sequence<220>
<223>Apo39<400>217gaattcattg tactcccagt atcattatag tgaaagtttt ggctctctcg ccggtggttt60tttacctcta tttaaagggg ttttccacct aaaaattctg gtatcattct cactttactt120gttactttaa tttctcataa tctttggttg aaattatcac gcttccgcac acgatatccc180tacaaattta ttatttgtta aacattttca aaccgcataa aattttatga agtcccgtct240atctttaatg tagtctaaca ttttcatatt gaaatatata atttacttaa ttttagcgtt300ggtagaaagc ataaagattt attcttattc ttcttcatat aaatgtttaa tatacaatat360
aaacaaattc tttaccttaa gaaggatttc ccattttata ttttaaaaat atatttatca420aatatttttc aaccacgtaa atctcataat aataagttgt ttcaaaagta ataaaattta480actccataat ttttttattc gactgatctt aaagcaacac ccagtgacac aactagccat540ttttttcttt gaataaaaaa atccaattat cattgtattt tttttataca atgaaaattt600caccaaacaa tcatttgtgg tatttctgaa gcaagtcatg ttatgcaaaa ttctataatt660cccatttgac actacggaag taactgaaga tctgctttta catgcgagac acatcttcta720aagtaatttt aataatagtt actatattca agatttcata tatcaaatac tcaatattac780ttctaaaaaa ttaattagat ataattaaaa tattactttt ttaattttaa gtttaattgt840tgaatttgtg actattgatt tattattcta ctatgtttaa attgttttat agatagttta900aagtaaatat aagtaatgta gtagagtgtt agagtgttac cctaaaccat aaactataac960atttatggtg gactaatttt catatatttc ttattgcttt taccttttct tggtatgtaa1020gtccgtaact agaattacag tgggttgcca tgacactctg tggtcttttg gttcatgcat1080gggtcttgcg caagaaaaag acaaagaaca aagaaaaaag acaaaacaga gagacaaaac1140gcaatcacac aaccaactca aattagtcac tggctgatca agatcgccgc gtccatgtat1200gtctaaatgc catgcaaagc aacacgtgct taacatgcac tttaaatggc tcacccatct1260caacccacac acaaacacat tgcctttttc ttcatcatca ccacaaccac ctgtatatat1320tcattctctt ccgccacctc aatttcttca cttcaacaca cgtcaacctg catatgcgtg1380tcatcccatg cccaaatctc catgcatgtt ccaaccacct tctctcttat ataataccta1440taaatacctc taatatcact cacttctttc atcatccatc catccagagt actactactc1500tactactata ataccccaac ccaactcata ttcaatacta ctctaccatg aacttcctta1560agtctttccc tttctacgct ttcctttgtt tcggtcaata cttcgttgct gttacgcatg1620ctgacattgt gatgacacag tctccatcct ccctggctat gtcagtggga cagcgggtca1680ctatgcgctg caagtccagt cagagccttt taaaaagtac caatcaaaag aactatttgg1740cctggtacca gcagaaacca ggacagtctc ctaaacttct ggtatacttt gcatccacta1800gggaatctgg ggtccctgat cgcttcatag gcagtggatc tgggacagat ttcactctta1860ccatcagcag tgtgcaggct gaagacctgg cagattactt ctgtcagcaa cattataaca1920ctcctcccac gttcggtgct gggaccaagc tggagcttaa gcggtctccg aacggtgctt1980ctcatagcgg ttctgcacca ggcactagct ctgcatctgg atctcaggtg cacctgcagc2040agtctggagc tgagctgatg aagcctgggg cctcaatgaa gatatcctgc aaggctactg2100
gctacacatt cagtagctac tggatagagt gggtaaagca gaggcctgga catggccttg2160agtggattgg agagatttta cctggcagtg gtagtactac ctacaatgag aagttcaagg2220gcaaggccac attcactgca gatacatcct ccaacacagc ctacatgcaa ctcagcagcc2280tgacatctga ggactctgcc gtctattact gtgcaagatt ggatgttgac tcctggggcc2340aaggcaccac tctcacagtc tcgactatgg ctgagatcac ccgcattcct ctctacaaag2400gtaagtctct ccgtaaggcg ctgaaggaac atggacttct agaagacttc ttgcagaaac2460aacagtatgg catctcgagc aagttcgatg aaccccccca gagcccctgg gatcgagtga2520aggacctggc cactgtgtac gtggatgtgc tcaaagacag cggcagagac tatgtgtccc2580agtttgaagg ctccgccttg ggaaaacagc taaacctaaa gctccttgac aactgggaca2640gcgtgacctc caccttcagc aagctgcgcg aacagctcgg ccctgtgacc caggagttct2700gggataacct ggaaaaggag acagagggcc tgaggcagga gatgagcaag gatctggagg2760aggtgaaggc caaggtgcag ccctacctgg acgacttcca gaagaagtgg caggaggaga2820tggagctcta ccgccagaag gtggagccgc tgcgcgcaga gctccaagag ggcgcgcgcc2880agaagctgca cgagctgcaa gagaagctga gcccactggg cgaggagatg cgcgaccgcg2940cgcgcgccca tgtggacgcg ctgcgcacgc atctggcccc ctacagcgac gagctgcgcc3000agcgcttggc cgcgcgcctt gaggctctca aggagaacgg cggcgccaga ctggccgagt3060accacgccaa ggccaccgag catctgagca cgctcagcga gaaggccaag cccgcgctag3120aggacctccg ccaaggcctg ctgcccgtgc tggagagctt caaggtcagc ttcctgagcg3180ctctggagga gtacactaag aagctcaaca cccagtgaaa gcttaaataa gtatgaacta3240aaatgcatgt aggtgtaaga gctcatggag agcatggaat attgtatccg accatgtaac3300agtataataa ctgagctcca tctcacttct tctatgaata aacaaaggat gttatgatat3360attaacactc tatctatgca ccttattgtt ctatgataaa tttcctctta ttattataaa3420tcatctgaat cgtgacggct tatggaatgc ttcaaatagt acaaaaacaa atgtgtacta3480taagactttc taaacaattc taactttagc attgtgaacg agacataagt gttaagaaga3540cataacaatt ataatggaag aagtttgtct ccatttatat attatatatt acccacttat3600gtattatatt aggatgttaa ggagacataa caattataaa gagagaagtt tgtatccatt3660tatatattat atactaccca tttatatatt atacttatcc acttatttaa tgtctttata3720aggtttgatc catgatattt ctaatatttt agttgatatg tatatgaaaa ggtactattt3780gaactctctt actctgtata aaggttggat catccttaaa gtgggtctat ttaattttat3840tgcttcttac agataaaaaa aaaattatga gttggtttga taaaatattg aaggatttaa3900
aataataata aataataaat aacatataat atatgtatat aaatttatta taatataaca3960tttatctata aaaaagtaaa tattgtcata aatctataca atcgtttagc cttgctggaa4020cgaatctcaa ttatttaaac gagagtaaac atatttgact ttttggttat ttaacaaatt4080attatttaac actatatgaa attttttttt tttatcagca aagaaataaa attaaattaa4140gaaggacaat ggtgtgtccc aatccttata caaccaactt ccacaagaaa gtcaagtcag4200agacaacaaa aaaacaagca aaggaaattt tttaatttga gttgtcttgt ttgctgcata4260atttatgcag taaaacacta cacataaccc ttttagcagt agagcaatgg ttgaccgtgt4320gcttagcttc ttttatttta tttttttatc agcaaagaat aaataaaata aaatgagaca4380cttcagggat gtttcaaccc ttatacaaaa ccccaaaaac aagtttccta gcaccctacc4440aactaa 4446<210>218<211>556<212>PRT<213>Artificial Sequence<220>
<223>Apo39<400>218Met Asn Phe Leu Lys Ser Phe Pro Phe Tyr Ala Phe Leu Cys Phe Gly1 5 10 15Gln Tyr Phe Val Ala Val Thr His Ala Asp Ile Val Met Thr Gln Ser20 25 30Pro Ser Ser Leu Ala Met Ser Val Gly Gln Arg Val Thr Met Arg Cys35 40 45Lys Ser Ser Gln Ser Leu Leu Lys Ser Thr Asn Gln Lys Asn Tyr Leu50 55 60Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Val Tyr65 70 75 80Phe Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ile Gly Ser85 90 95Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Val Gln Ala Glu100 105 110
Asp Leu Ala Asp Tyr Phe Cys Gln Gln His Tyr Asn Thr Pro Pro Thr115 120 125Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys Arg Ser Pro Asn Gly Ala130 135 140Ser His Ser Gly Ser Ala Pro Gly Thr Ser Ser Ala Ser Gly Ser Gln145 150 155 160Val His Leu Gln Gln Ser Gly Ala Glu Leu Met Lys Pro Gly Ala Ser165 170 175Met Lys Ile Ser Cys Lys Ala Thr Gly Tyr Thr Phe Ser Ser Tyr Trp180 185 190Ile Glu Trp Val Lys Gln Arg Pro Gly His Gly Leu Glu Trp Ile Gly195 200 205Glu Ile Leu Pro Gly Ser Gly Ser Thr Thr Tyr Asn Glu Lys Phe Lys210 215 220Gly Lys Ala Thr Phe Thr Ala Asp Thr Ser Ser Asn Thr Ala Tyr Met225 230 235 240Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys Ala245 250 255Arg Leu Asp Val Asp Ser Trp Gly Gln Gly Thr Thr Leu Thr Val Ser260 265 270Thr Met Ala Glu Ile Thr Arg Ile Pro Leu Tyr Lys Gly Lys Ser Leu275 280 285Arg Lys Ala Leu Lys Glu His Gly Leu Leu Glu Asp Phe Leu Gln Lys290 295 300Gln Gln Tyr Gly Ile Ser Ser Lys Phe Asp Glu Pro Pro Gln Ser Pro305 310 315 320Trp Asp Arg Val Lys Asp Leu Ala Thr Val Tyr Val Asp Val Leu Lys325 330 335Asp Ser Gly Arg Asp Tyr Val Ser Gln Phe Glu Gly Ser Ala Leu Gly340 345 350
Lys Gln Leu Asn Leu Lys Leu Leu Asp Asn Trp Asp Ser Val Thr Ser355 360 365Thr Phe Ser Lys Leu Arg Glu Gln Leu Gly Pro Val Thr Gln Glu Phe370 375 380Trp Asp Asn Leu Glu Lys Glu Thr Glu Gly Leu Arg Gln Glu Met Ser385 390 395 400Lys Asp Leu Glu Glu Val Lys Ala Lys Val Gln Pro Tyr Leu Asp Asp405 410 415Phe Gln Lys Lys Trp Gln Glu Glu Met Glu Leu Tyr Arg Gln Lys Val420 425 430Glu Pro Leu Arg Ala Glu Leu Gln Glu Gly Ala Arg Gln Lys Leu His435 440 445Glu Leu Gln Glu Lys Leu Ser Pro Leu Gly Glu Glu Met Arg Asp Arg450 455 460Ala Arg Ala His Val Asp Ala Leu Arg Thr His Leu Ala Pro Tyr Ser465 470 475 480Asp Glu Leu Arg Gln Arg Leu Ala Ala Arg Leu Glu Ala Leu Lys Glu485 490 495Asn Gly Gly Ala Arg Leu Ala Glu Tyr His Ala Lys Ala Thr Glu His500 505 510Leu Ser Thr Leu Ser Glu Lys Ala Lys Pro Ala Leu Glu Asp Leu Arg515 520 525Gln Gly Leu Leu Pro Val Leu Glu Ser Phe Lys Val Ser Phe Leu Ser530 535 540Ala Leu Glu Glu Tyr Thr Lys Lys Leu Asn Thr Gln545 550 555<210>219<211>35<212>DNA<213>Artificial Sequence
<220>
<223>forward primer 1207<400>219gcagcagtcg actatggctg agatcacccg cattc 35<210>220<211>4464<212>DNA<213>Artificial Sequence<220>
<223>Apo40<400>220gaattcattg tactcccagt atcattatag tgaaagtttt ggctctctcg ccggtggttt 60tttacctcta tttaaagggg ttttccacct aaaaattctg gtatcattct cactttactt 120gttactttaa tttctcataa tctttggttg aaattatcac gcttccgcac acgatatccc 180tacaaattta ttatttgtta aacattttca aaccgcataa aattttatga agtcccgtct 240atctttaatg tagtctaaca ttttcatatt gaaatatata atttacttaa ttttagcgtt 300ggtagaaagc ataaagattt attcttattc ttcttcatat aaatgtttaa tatacaatat 360aaacaaattc tttaccttaa gaaggatttc ccattttata ttttaaaaat atatttatca 420aatatttttc aaccacgtaa atctcataat aataagttgt ttcaaaagta ataaaattta 480actccataat ttttttattc gactgatctt aaagcaacac ccagtgacac aactagccat 540ttttttcttt gaataaaaaa atccaattat cattgtattt tttttataca atgaaaattt 600caccaaacaa tcatttgtgg tatttctgaa gcaagtcatg ttatgcaaaa ttctataatt 660cccatttgac actacggaag taactgaaga tctgctttta catgcgagac acatcttcta 720aagtaatttt aataatagtt actatattca agatttcata tatcaaatac tcaatattac 780ttctaaaaaa ttaattagat ataattaaaa tattactttt ttaattttaa gtttaattgt 840tgaatttgtg actattgatt tattattcta ctatgtttaa attgttttat agatagttta 900aagtaaatat aagtaatgta gtagagtgtt agagtgttac cctaaaccat aaactataac 960atttatggtg gactaatttt catatatttc ttattgcttt taccttttct tggtatgtaa1020gtccgtaact agaattacag tgggttgcca tgacactctg tggtcttttg gttcatgcat1080gggtcttgcg caagaaaaag acaaagaaca aagaaaaaag acaaaacaga gagacaaaac1140gcaatcacac aaccaactca aattagtcac tggctgatca agatcgccgc gtccatgtat1200gtctaaatgc catgcaaagc aacacgtgct taacatgcac tttaaatggc tcacccatct1260caacccacac acaaacacat tgcctttttc ttcatcatca ccacaaccac ctgtatatat1320
tcattctctt ccgccacctc aatttcttca cttcaacaca cgtcaacctg catatgcgtg1380tcatcccatg cccaaatctc catgcatgtt ccaaccacct tctctcttat ataataccta1440taaatacctc taatatcact cacttctttc atcatccatc catccagagt actactactc1500tactactata ataccccaac ccaactcata ttcaatacta ctctaccatg aacttcctta1560agtctttccc tttctacgct ttcctttgtt tcggtcaata cttcgttgct gttacgcatg1620ctgacattgt gatgacacag tctccatcct ccctggctat gtcagtggga cagcgggtca1680ctatgcgctg caagtccagt cagagccttt taaaaagtac caatcaaaag aactatttgg1740cctggtacca gcagaaacca ggacagtctc ctaaacttct ggtatacttt gcatccacta1800gggaatctgg ggtccctgat cgcttcatag gcagtggatc tgggacagat ttcactctta1860ccatcagcag tgtgcaggct gaagacctgg cagattactt ctgtcagcaa cattataaca1920ctcctcccac gttcggtgct gggaccaagc tggagcttaa gcggtctccg aacggtgctt1980ctcatagcgg ttctgcacca ggcactagct ctgcatctgg atctcaggtg cacctgcagc2040agtctggagc tgagctgatg aagcctgggg cctcaatgaa gatatcctgc aaggctactg2100gctacacatt cagtagctac tggatagagt gggtaaagca gaggcctgga catggccttg2160agtggattgg agagatttta cctggcagtg gtagtactac ctacaatgag aagttcaagg2220gcaaggccac attcactgca gatacatcct ccaacacagc ctacatgcaa ctcagcagcc2280tgacatctga ggactctgcc gtctattact gtgcaagatt ggatgttgac tcctggggcc2340aaggcaccac tctcacagtc tcgactatgg ctgagatcac ccgcattcct ctctacaaag2400gtaagtctct ccgtaaggcg ctgaaggaac atggacttct agaagacttc ttgcagaaac2460aacagtatgg catctcgagc aagttccggc atttctggca gcaagatgaa cccccccaga2520gcccctggga tcgagtgaag gacctggcca ctgtgtacgt ggatgtgctc aaagacagcg2580gcagagacta tgtgtcccag tttgaaggct ccgccttggg aaaacagcta aacctaaagc2640tccttgacaa ctgggacagc gtgacctcca ccttcagcaa gctgcgcgaa cagctcggcc2700ctgtgaccca ggagttctgg gataacctgg aaaaggagac agagggcctg aggcaggaga2760tgagcaagga tctggaggag gtgaaggcca aggtgcagcc ctacctggac gacttccaga2820agaagtggca ggaggagatg gagctctacc gccagaaggt ggagccgctg cgcgcagagc2880tccaagaggg cgcgcgccag aagctgcacg agctgcaaga gaagctgagc ccactgggcg2940aggagatgcg cgaccgcgcg cgcgcccatg tggacgcgct gcgcacgcat ctggccccct3000acagcgacga gctgcgccag cgcttggccg cgcgccttga ggctctcaag gagaacggcg3060
gcgccagact ggccgagtac cacgccaagg ccaccgagca tctgagcacg ctcagcgaga3120aggccaagcc cgcgctagag gacctccgcc aaggcctgct gcccgtgctg gagagcttca3180aggtcagctt cctgagcgct ctggaggagt acactaagaa gctcaacacc cagtgaaagc3240ttaaataagt atgaactaaa atgcatgtag gtgtaagagc tcatggagag catggaatat3300tgtatccgac catgtaacag tataataact gagctccatc tcacttcttc tatgaataaa3360caaaggatgt tatgatatat taacactcta tctatgcacc ttattgttct atgataaatt3420tcctcttatt attataaatc atctgaatcg tgacggctta tggaatgctt caaatagtac3480aaaaacaaat gtgtactata agactttcta aacaattcta actttagcat tgtgaacgag3540acataagtgt taagaagaca taacaattat aatggaagaa gtttgtctcc atttatatat3600tatatattac ccacttatgt attatattag gatgttaagg agacataaca attataaaga3660gagaagtttg tatccattta tatattatat actacccatt tatatattat acttatccac3720ttatttaatg tctttataag gtttgatcca tgatatttct aatattttag ttgatatgta3780tatgaaaagg tactatttga actctcttac tctgtataaa ggttggatca tccttaaagt3840gggtctattt aattttattg cttcttacag ataaaaaaaa aattatgagt tggtttgata3900aaatattgaa ggatttaaaa taataataaa taataaataa catataatat atgtatataa3960atttattata atataacatt tatctataaa aaagtaaata ttgtcataaa tctatacaat4020cgtttagcct tgctggaacg aatctcaatt atttaaacga gagtaaacat atttgacttt4080ttggttattt aacaaattat tatttaacac tatatgaaat tttttttttt tatcagcaaa4140gaaataaaat taaattaaga aggacaatgg tgtgtcccaa tccttataca accaacttcc4200acaagaaagt caagtcagag acaacaaaaa aacaagcaaa ggaaattttt taatttgagt4260tgtcttgttt gctgcataat ttatgcagta aaacactaca cataaccctt ttagcagtag4320agcaatggtt gaccgtgtgc ttagcttctt ttattttatt tttttatcag caaagaataa4380ataaaataaa atgagacact tcagggatgt ttcaaccctt atacaaaacc ccaaaaacaa4440gtttcctagc accctaccaa ctaa 4464<210>221<211>562<212>PRT<213>Artificial Sequence<220>
<223>Apo40<400>221
Met Asn Phe Leu Lys Ser Phe Pro Phe Tyr Ala Phe Leu Cys Phe Gly1 5 10 15Gln Tyr Phe Val Ala Val Thr His Ala Asp Ile Val Met Thr Gln Ser20 25 30Pro Ser Ser Leu Ala Met Ser Val Gly Gln Arg Val Thr Met Arg Cys35 40 45Lys Ser Ser Gln Ser Leu Leu Lys Ser Thr Asn Gln Lys Asn Tyr Leu50 55 60Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Val Tyr65 70 75 80Phe Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ile Gly Ser85 90 95Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Val Gln Ala Glu100 105 110Asp Leu Ala Asp Tyr Phe Cys Gln Gln His Tyr Asn Thr Pro Pro Thr115 120 125Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys Arg Ser Pro Asn Gly Ala130 135 140Ser His Ser Gly Ser Ala Pro Gly Thr Ser Ser Ala Ser Gly Ser Gln145 150 155 160Val His Leu Gln Gln Ser Gly Ala Glu Leu Met Lys Pro Gly Ala Ser165 170 175Met Lys Ile Ser Cys Lys Ala Thr Gly Tyr Thr Phe Ser Ser Tyr Trp180 185 190Ile Glu Trp Val Lys Gln Arg Pro Gly His Gly Leu Glu Trp Ile Gly195 200 205Glu Ile Leu Pro Gly Ser Gly Ser Thr Thr Tyr Asn Glu Lys Phe Lys210 215 220Gly Lys Ala Thr Phe Thr Ala Asp Thr Ser Ser Asn Thr Ala Tyr Met225 230 235 240
Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys Ala245 250 255Arg Leu Asp Val Asp Ser Trp Gly Gln Gly Thr Thr Leu Thr Val Ser260 265 270Thr Met Ala Glu Ile Thr Arg Ile Pro Leu Tyr Lys Gly Lys Ser Leu275 280 285Arg Lys Ala Leu Lys Glu His Gly Leu Leu Glu Asp Phe Leu Gln Lys290 295 300Gln Gln Tyr Gly Ile Ser Ser Lys Phe Arg His Phe Trp Gln Gln Asp305 310 315 320Glu Pro Pro Gln Ser Pro Trp Asp Arg Val Lys Asp Leu Ala Thr Val325 330 335Tyr Val Asp Val Leu Lys Asp Ser Gly Arg Asp Tyr Val Ser Gln Phe340 345 350Glu Gly Ser Ala Leu Gly Lys Gln Leu Asn Leu Lys Leu Leu Asp Asn355 360 365Trp Asp Ser Val Thr Ser Thr Phe Ser Lys Leu Arg Glu Gln Leu Gly370 375 380Pro Val Thr Gln Glu Phe Trp Asp Asn Leu Glu Lys Glu Thr Glu Gly385 390 395 400Leu Arg Gln Glu Met Ser Lys Asp Leu Glu Glu Val Lys Ala Lys Val405 410 415Gln Pro Tyr Leu Asp Asp Phe Gln Lys Lys Trp Gln Glu Glu Met Glu420 425 430Leu Tyr Arg Gln Lys Val Glu Pro Leu Arg Ala Glu Leu Gln Glu Gly435 440 445Ala Arg Gln Lys Leu His Glu Leu Gln Glu Lys Leu Ser Pro Leu Gly450 455 460Glu Glu Met Arg Asp Arg Ala Arg Ala His Val Asp Ala Leu Arg Thr465 470 475 480
His Leu Ala Pro Tyr Ser Asp Glu Leu Arg Gln Arg Leu Ala Ala Arg485 490 495Leu Glu Ala Leu Lys Glu Asn Gly Gly Ala Arg Leu Ala Glu Tyr His500 505 510Ala Lys Ala Thr Glu His Leu Ser Thr Leu Ser Glu Lys Ala Lys Pro515 520 525Ala Leu Glu Asp Leu Arg Gln Gly Leu Leu Pro Val Leu Glu Ser Phe530 535 540Lys Val Ser Phe Leu Ser Ala Leu Glu Glu Tyr Thr Lys Lys Leu Asn545 550 555 560Thr Gln<210>222<211>4449<212>DNA<213>Artificial Sequence<220>
<223>Apo41<400>222gaattcattg tactcccagt atcattatag tgaaagtttt ggctctctcg ccggtggttt 60tttacctcta tttaaagggg ttttccacct aaaaattctg gtatcattct cactttactt120gttactttaa tttctcataa tctttggttg aaattatcac gcttccgcac acgatatccc180tacaaattta ttatttgtta aacattttca aaccgcataa aattttatga agtcccgtct240atctttaatg tagtctaaca ttttcatatt gaaatatata atttacttaa ttttagcgtt300ggtagaaagc ataaagattt attcttattc ttcttcatat aaatgtttaa tatacaatat360aaacaaattc tttaccttaa gaaggatttc ccattttata ttttaaaaat atatttatca420aatatttttc aaccacgtaa atctcataat aataagttgt ttcaaaagta ataaaattta480actccataat ttttttattc gactgatctt aaagcaacac ccagtgacac aactagccat540ttttttcttt gaataaaaaa atccaattat cattgtattt tttttataca atgaaaattt600caccaaacaa tcatttgtgg tatttctgaa gcaagtcatg ttatgcaaaa ttctataatt660cccatttgac actacggaag taactgaaga tctgctttta catgcgagac acatcttcta720
aagtaatttt aataatagtt actatattca agatttcata tatcaaatac tcaatattac 780ttctaaaaaa ttaattagat ataattaaaa tattactttt ttaattttaa gtttaattgt 840tgaatttgtg actattgatt tattattcta ctatgtttaa attgttttat agatagttta 900aagtaaatat aagtaatgta gtagagtgtt agagtgttac cctaaaccat aaactataac 960atttatggtg gactaatttt catatatttc ttattgcttt taccttttct tggtatgtaa1020gtccgtaact agaattacag tgggttgcca tgacactctg tggtcttttg gttcatgcat1080gggtcttgcg caagaaaaag acaaagaaca aagaaaaaag acaaaacaga gagacaaaac1140gcaatcacac aaccaactca aattagtcac tggctgatca agatcgccgc gtccatgtat1200gtctaaatgc catgcaaagc aacacgtgct taacatgcac tttaaatggc tcacccatct1260caacccacac acaaacacat tgcctttttc ttcatcatca ccacaaccac ctgtatatat1320tcattctctt ccgccacctc aatttcttca cttcaacaca cgtcaacctg catatgcgtg1380tcatcccatg cccaaatctc catgcatgtt ccaaccacct tctctcttat ataataccta1440taaatacctc taatatcact cacttctttc atcatccatc catccagagt actactactc1500tactactata ataccccaac ccaactcata ttcaatacta ctctaccatg aacttcctta1560agtctttccc tttctacgct ttcctttgtt tcggtcaata cttcgttgct gttacgcatg1620ctgacattgt gatgacacag tctccatcct ccctggctat gtcagtggga cagcgggtca1680ctatgcgctg caagtccagt cagagccttt taaaaagtac caatcaaaag aactatttgg1740cctggtacca gcagaaacca ggacagtctc ctaaacttct ggtatacttt gcatccacta1800gggaatctgg ggtccctgat cgcttcatag gcagtggatc tgggacagat ttcactctta1860ccatcagcag tgtgcaggct gaagacctgg cagattactt ctgtcagcaa cattataaca1920ctcctcccac gttcggtgct gggaccaagc tggagcttaa gcggtctccg aacggtgctt1980ctcatagcgg ttctgcacca ggcactagct ctgcatctgg atctcaggtg cacctgcagc2040agtctggagc tgagctgatg aagcctgggg cctcaatgaa gatatcctgc aaggctactg2100gctacacatt cagtagctac tggatagagt gggtaaagca gaggcctgga catggccttg2160agtggattgg agagatttta cctggcagtg gtagtactac ctacaatgag aagttcaagg2220gcaaggccac attcactgca gatacatcct ccaacacagc ctacatgcaa ctcagcagcc2280tgacatctga ggactctgcc gtctattact gtgcaagatt ggatgttgac tcctggggcc2340aaggcaccac tctcacagtc tcgactatgg ctgagatcac ccgcattcct ctctacaaag2400gtaagtctct ccgtaaggcg ctgaaggaac atggacttct agaagacttc ttgcagaaac2460aacagtatgg catctcgagc aagttcatgg atgaaccccc ccagagcccc tgggatcgag2520
tgaaggacct ggccactgtg tacgtggatg tgctcaaaga cagcggcaga gactatgtgt2580cccagtttga aggctccgcc ttgggaaaac agctaaacct aaagctcctt gacaactggg2640acagcgtgac ctccaccttc agcaagctgc gcgaacagct cggccctgtg acccaggagt2700tctgggataa cctggaaaag gagacagagg gcctgaggca ggagatgagc aaggatctgg2760aggaggtgaa ggccaaggtg cagccctacc tggacgactt ccagaagaag tggcaggagg2820agatggagct ctaccgccag aaggtggagc cgctgcgcgc agagctccaa gagggcgcgc2880gccagaagct gcacgagctg caagagaagc tgagcccact gggcgaggag atgcgcgacc2940gcgcgcgcgc ccatgtggac gcgctgcgca cgcatctggc cccctacagc gacgagctgc3000gccagcgctt ggccgcgcgc cttgaggctc tcaaggagaa cggcggcgcc agactggccg3060agtaccacgc caaggccacc gagcatctga gcacgctcag cgagaaggcc aagcccgcgc3120tcgaggacct ccgccaaggc ctgctgcccg tgctggagag cttcaaggtc agcttcctga3180gcgctctgga ggagtacact aagaagctca acacccagtg aaagcttaaa taagtatgaa3240ctaaaatgca tgtaggtgta agagctcatg gagagcatgg aatattgtat ccgaccatgt3300aacagtataa taactgagct ccatctcact tcttctatga ataaacaaag gatgttatga3360tatattaaca ctctatctat gcaccttatt gttctatgat aaatttcctc ttattattat3420aaatcatctg aatcgtgacg gcttatggaa tgcttcaaat agtacaaaaa caaatgtgta3480ctataagact ttctaaacaa ttctaacttt agcattgtga acgagacata agtgttaaga3540agacataaca attataatgg aagaagtttg tctccattta tatattatat attacccact3600tatgtattat attaggatgt taaggagaca taacaattat aaagagagaa gtttgtatcc3660atttatatat tatatactac ccatttatat attatactta tccacttatt taatgtcttt3720ataaggtttg atccatgata tttctaatat tttagttgat atgtatatga aaaggtacta3780tttgaactct cttactctgt ataaaggttg gatcatcctt aaagtgggtc tatttaattt3840tattgcttct tacagataaa aaaaaaatta tgagttggtt tgataaaata ttgaaggatt3900taaaataata ataaataata aataacatat aatatatgta tataaattta ttataatata3960acatttatct ataaaaaagt aaatattgtc ataaatctat acaatcgttt agccttgctg4020gaacgaatct caattattta aacgagagta aacatatttg actttttggt tatttaacaa4080attattattt aacactatat gaaatttttt ttttttatca gcaaagaaat aaaattaaat4140taagaaggac aatggtgtgt cccaatcctt atacaaccaa cttccacaag aaagtcaagt4200cagagacaac aaaaaaacaa gcaaaggaaa ttttttaatt tgagttgtct tgtttgctgc4260
ataatttatg cagtaaaaca ctacacataa cccttttagc agtagagcaa tggttgaccg4320tgtgcttagc ttcttttatt ttattttttt atcagcaaag aataaataaa ataaaatgag4380acacttcagg gatgtttcaa cccttataca aaaccccaaa aacaagtttc ctagcaccct4440accaactaa4449<210>223<211>557<212>PRT<213>Artificial Sequence<220>
<223>Apo41<400>223Met Asn Phe Leu Lys Ser Phe Pro Phe Tyr Ala Phe Leu Cys Phe Gly1 5 10 15Gln Tyr Phe Val Ala Val Thr His Ala Asp Ile Val Met Thr Gln Ser20 25 30Pro Ser Ser Leu Ala Met Ser Val Gly Gln Arg Val Thr Met Arg Cys35 40 45Lys Ser Ser Gln Ser Leu Leu Lys Ser Thr Asn Gln Lys Asn Tyr Leu50 55 60Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Val Tyr65 70 75 80Phe Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ile Gly Ser85 90 95Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Val Gln Ala Glu100 105 110Asp Leu Ala Asp Tyr Phe Cys Gln Gln His Tyr Asn Thr Pro Pro Thr115 120 125Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys Arg Ser Pro Asn Gly Ala130 135 140Ser His Ser Gly Ser Ala Pro Gly Thr Ser Ser Ala Ser Gly Ser Gln145 150 155 160
Val His Leu Gln Gln Ser Gly Ala Glu Leu Met Lys Pro Gly Ala Ser165 170 175Met Lys Ile Ser Cys Lys Ala Thr Gly Tyr Thr Phe Ser Ser Tyr Trp180 185 190Ile Glu Trp Val Lys Gln Arg Pro Gly His Gly Leu Glu Trp Ile Gly195 200 205Glu Ile Leu Pro Gly Ser Gly Ser Thr Thr Tyr Asn Glu Lys Phe Lys210 215 220Gly Lys Ala Thr Phe Thr Ala Asp Thr Ser Ser Asn Thr Ala Tyr Met225 230 235 240Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys Ala245 250 255Arg Leu Asp Val Asp Ser Trp Gly Gln Gly Thr Thr Leu Thr Val Ser260 265 270Thr Met Ala Glu Ile Thr Arg Ile Pro Leu Tyr Lys Gly Lys Ser Leu275 280 285Arg Lys Ala Leu Lys Glu His Gly Leu Leu Glu Asp Phe Leu Gln Lys290 295 300Gln Gln Tyr Gly Ile Ser Ser Lys Phe Met Asp Glu Pro Pro Gln Ser305 310 315 320Pro Trp Asp Arg Val Lys Asp Leu Ala Thr Val Tyr Val Asp Val Leu325 330 335Lys Asp Ser Gly Arg Asp Tyr Val Ser Gln Phe Glu Gly Ser Ala Leu340 345 350Gly Lys Gln Leu Asn Leu Lys Leu Leu Asp Asn Trp Asp Ser Val Thr355 360 365Ser Thr Phe Ser Lys Leu Arg Glu Gln Leu Gly Pro Val Thr Gln Glu370 375 380Phe Trp Asp Asn Leu Glu Lys Glu Thr Glu Gly Leu Arg Gln Glu Met385 390 395 400
Ser Lys Asp Leu Glu Glu Val Lys Ala Lys Val Gln Pro Tyr Leu Asp405 410 415Asp Phe Gln Lys Lys Trp Gln Glu Glu Met Glu Leu Tyr Arg Gln Lys420 425 430Val Glu Pro Leu Arg Ala Glu Leu Gln Glu Gly Ala Arg Gln Lys Leu435 440 445His Glu Leu Gln Glu Lys Leu Ser Pro Leu Gly Glu Glu Met Arg Asp450 455 460Arg Ala Arg Ala His Val Asp Ala Leu Arg Thr His Leu Ala Pro Tyr465 470 475 480Ser Asp Glu Leu Arg Gln Arg Leu Ala Ala Arg Leu Glu Ala Leu Lys485 490 495Glu Asn Gly Gly Ala Arg Leu Ala Glu Tyr His Ala Lys Ala Thr Glu500 505 510His Leu Ser Thr Leu Ser Glu Lys Ala Lys Pro Ala Leu Glu Asp Leu515 520 525Arg Gln Gly Leu Leu Pro Val Leu Glu Ser Phe Lys Val Ser Phe Leu530 535 540Ser Ala Leu Glu Glu Tyr Thr Lys Lys Leu Asn Thr Gln545 550 555<210>224<211>4470<212>DNA<213>Artificial Sequence<220>
<223>Apo42<400>224gaattcattg tactcccagt atcattatag tgaaagtttt ggctctctcg ccggtggttt 60tttacctcta tttaaagggg ttttccacct aaaaattctg gtatcattct cactttactt120gttactttaa tttctcataa tctttggttg aaattatcac gcttccgcac acgatatccc180tacaaattta ttatttgtta aacattttca aaccgcataa aattttatga agtcccgtct240atctttaatg tagtctaaca ttttcatatt gaaatatata atttacttaa ttttagcgtt300
ggtagaaagc ataaagattt attcttattc ttcttcatat aaatgtttaa tatacaatat 360aaacaaattc tttaccttaa gaaggatttc ccattttata ttttaaaaat atatttatca 420aatatttttc aaccacgtaa atctcataat aataagttgt ttcaaaagta ataaaattta 480actccataat ttttttattc gactgatctt aaagcaacac ccagtgacac aactagccat 540ttttttcttt gaataaaaaa atccaattat cattgtattt tttttataca atgaaaattt 600caccaaacaa tcatttgtgg tatttctgaa gcaagtcatg ttatgcaaaa ttctataatt 660cccatttgac actacggaag taactgaaga tctgctttta catgcgagac acatcttcta 720aagtaatttt aataatagtt actatattca agatttcata tatcaaatac tcaatattac 780ttctaaaaaa ttaattagat ataattaaaa tattactttt ttaattttaa gtttaattgt 840tgaatttgtg actattgatt tattattcta ctatgtttaa attgttttat agatagttta 900aagtaaatat aagtaatgta gtagagtgtt agagtgttac cctaaaccat aaactataac 960atttatggtg gactaatttt catatatttc ttattgcttt taccttttct tggtatgtaa1020gtccgtaact agaattacag tgggttgcca tgacactctg tggtcttttg gttcatgcat1080gggtcttgcg caagaaaaag acaaagaaca aagaaaaaag acaaaacaga gagacaaaac1140gcaatcacac aaccaactca aattagtcac tggctgatca agatcgccgc gtccatgtat1200gtctaaatgc catgcaaagc aacacgtgct taacatgcac tttaaatggc tcacccatct1260caacccacac acaaacacat tgcctttttc ttcatcatca ccacaaccac ctgtatatat1320tcattctctt ccgccacctc aatttcttca cttcaacaca cgtcaacctg catatgcgtg1380tcatcccatg cccaaatctc catgcatgtt ccaaccacct tctctcttat ataataccta1440taaatacctc taatatcact cacttctttc atcatccatc catccagagt actactactc1500tactactata ataccccaac ccaactcata ttcaatacta ctctaccatg aacttcctta1560agtctttccc tttctacgct ttcctttgtt tcggtcaata cttcgttgct gttacgcatg1620ctgacattgt gatgacacag tctccatcct ccctggctat gtcagtggga cagcgggtca1680ctatgcgctg caagtccagt cagagccttt taaaaagtac caatcaaaag aactatttgg1740cctggtacca gcagaaacca ggacagtctc ctaaacttct ggtatacttt gcatccacta1800gggaatctgg ggtccctgat cgcttcatag gcagtggatc tgggacagat ttcactctta1860ccatcagcag tgtgcaggct gaagacctgg cagattactt ctgtcagcaa cattataaca1920ctcctcccac gttcggtgct gggaccaagc tggagcttaa gcggtctccg aacggtgctt1980ctcatagcgg ttctgcacca ggcactagct ctgcatctgg atctcaggtg cacctgcagc2040
agtctggagc tgagctgatg aagcctgggg cctcaatgaa gatatcctgc aaggctactg2100gctacacatt cagtagctac tggatagagt gggtaaagca gaggcctgga catggccttg2160agtggattgg agagatttta cctggcagtg gtagtactac ctacaatgag aagttcaagg2220gcaaggccac attcactgca gatacatcct ccaacacagc ctacatgcaa ctcagcagcc2280tgacatctga ggactctgcc gtctattact gtgcaagatt ggatgttgac tcctggggcc2340aaggcaccac tctcacagtc tcgactatgg ctgagatcac ccgcattcct ctctacaaag2400gtaagtctct ccgtaaggcg ctgaaggaac atggacttct agaagacttc ttgcagaaac2460aacagtatgg catctcgagc aagttcatgg ggcggcattt ctggcagcaa gatgaacccc2520cccagagccc ctgggatcga gtgaaggacc tggccactgt gtacgtggat gtgctcaaag2580acagcggcag agactatgtg tcccagtttg aaggctccgc cttgggaaaa cagctaaacc2640taaagctcct tgacaactgg gacagcgtga cctccacctt cagcaagctg cgcgaacagc2700tcggccctgt gacccaggag ttctgggata acctggaaaa ggagacagag ggcctgaggc2760aggagatgag caaggatctg gaggaggtga aggccaaggt gcagccctac ctggacgact2820tccagaagaa gtggcaggag gagatggagc tctaccgcca gaaggtggag ccgctgcgcg2880cagagctcca agagggcgcg cgccagaagc tgcacgagct gcaagagaag ctgagcccac2940tgggcgagga gatgcgcgac cgcgcgcgcg cccatgtgga cgcgctgcgc acgcatctgg3000ccccctacag cgacgagctg cgccagcgct tggccgcgcg ccttgaggct ctcaaggaga3060acggcggcgc cagactggcc gagtaccacg ccaaggccac cgagcatctg agcacgctca3120gcgagaaggc caagcccgcg ctcgaggacc tccgccaagg cctgctgccc gtgctggaga3180gcttcaaggt cagcttcctg agcgctctgg aggagtacac taagaagctc aacacccagt3240gaaagcttaa ataagtatga actaaaatgc atgtaggtgt aagagctcat ggagagcatg3300gaatattgta tccgaccatg taacagtata ataactgagc tccatctcac ttcttctatg3360aataaacaaa ggatgttatg atatattaac actctatcta tgcaccttat tgttctatga3420taaatttcct cttattatta taaatcatct gaatcgtgac ggcttatgga atgcttcaaa3480tagtacaaaa acaaatgtgt actataagac tttctaaaca attctaactt tagcattgtg3540aacgagacat aagtgttaag aagacataac aattataatg gaagaagttt gtctccattt3600atatattata tattacccac ttatgtatta tattaggatg ttaaggagac ataacaatta3660taaagagaga agtttgtatc catttatata ttatatacta cccatttata tattatactt3720atccacttat ttaatgtctt tataaggttt gatccatgat atttctaata ttttagttga3780tatgtatatg aaaaggtact atttgaactc tcttactctg tataaaggtt ggatcatcct3840
taaagtgggt ctatttaatt ttattgcttc ttacagataa aaaaaaaatt atgagttggt3900ttgataaaat attgaaggat ttaaaataat aataaataat aaataacata taatatatgt3960atataaattt attataatat aacatttatc tataaaaaag taaatattgt cataaatcta4020tacaatcgtt tagccttgct ggaacgaatc tcaattattt aaacgagagt aaacatattt4080gactttttgg ttatttaaca aattattatt taacactata tgaaattttt tttttttatc4140agcaaagaaa taaaattaaa ttaagaagga caatggtgtg tcccaatcct tatacaacca4200acttccacaa gaaagtcaag tcagagacaa caaaaaaaca agcaaaggaa attttttaat4260ttgagttgtc ttgtttgctg cataatttat gcagtaaaac actacacata acccttttag4320cagtagagca atggttgacc gtgtgcttag cttcttttat tttatttttt tatcagcaaa4380gaataaataa aataaaatga gacacttcag ggatgtttca acccttatac aaaaccccaa4440aaacaagttt cctagcaccc taccaactaa 4470<210>225<211>564<212>PRT<213>Artificial Sequence<220>
<223>Apo42<400>225Met Asn Phe Leu Lys Ser Phe Pro Phe Tyr Ala Phe Leu Cys Phe Gly1 5 10 15Gln Tyr Phe Val Ala Val Thr His Ala Asp Ile Val Met Thr Gln Ser20 25 30Pro Ser Ser Leu Ala Met Ser Val Gly Gln Arg Val Thr Met Arg Cys35 40 45Lys Ser Ser Gln Ser Leu Leu Lys Ser Thr Asn Gln Lys Asn Tyr Leu50 55 60Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Val Tyr65 70 75 80Phe Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ile Gly Ser85 90 95Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Val Gln Ala Glu
100 105 110Asp Leu Ala Asp Tyr Phe Cys Gln Gln His Tyr Asn Thr Pro Pro Thr115 120 125Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys Arg Ser Pro Asn Gly Ala130 135 140Ser His Ser Gly Ser Ala Pro Gly Thr Ser Ser Ala Ser Gly Ser Gln145 150 155 160Val His Leu Gln Gln Ser Gly Ala Glu Leu Met Lys Pro Gly Ala Ser165 170 175Met Lys Ile Ser Cys Lys Ala Thr Gly Tyr Thr Phe Ser Ser Tyr Trp180 185 190Ile Glu Trp Val Lys Gln Arg Pro Gly His Gly Leu Glu Trp Ile Gly195 200 205Glu Ile Leu Pro Gly Ser Gly Ser Thr Thr Tyr Asn Glu Lys Phe Lys210 215 220Gly Lys Ala Thr Phe Thr Ala Asp Thr Ser Ser Asn Thr Ala Tyr Met225 230 235 240Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys Ala245 250 255Arg Leu Asp Val Asp Ser Trp Gly Gln Gly Thr Thr Leu Thr Val Ser260 265 270Thr Met Ala Glu Ile Thr Arg Ile Pro Leu Tyr Lys Gly Lys Ser Leu275 280 285Arg Lys Ala Leu Lys Glu His Gly Leu Leu Glu Asp Phe Leu Gln Lys290 295 300Gln Gln Tyr Gly Ile Ser Ser Lys Phe Met Gly Arg His Phe Trp Gln305 310 315 320Gln Asp Glu Pro Pro Gln Ser Pro Trp Asp Arg Val Lys Asp Leu Ala325 330 335
Thr Val Tyr Val Asp Val Leu Lys Asp Ser Gly Arg Asp Tyr Val Ser340 345 350Gln Phe Glu Gly Ser Ala Leu Gly Lys Gln Leu Asn Leu Lys Leu Leu355 360 365Asp Asn Trp Asp Ser Val Thr Ser Thr Phe Ser Lys Leu Arg Glu Gln370 375 380Leu Gly Pro Val Thr Gln Glu Phe Trp Asp Asn Leu Glu Lys Glu Thr385 390 395 400Glu Gly Leu Arg Gln Glu Met Ser Lys Asp Leu Glu Glu Val Lys Ala405 410 415Lys Val Gln Pro Tyr Leu Asp Asp Phe Gln Lys Lys Trp Gln Glu Glu420 425 430Met Glu Leu Tyr Arg Gln Lys Val Glu Pro Leu Arg Ala Glu Leu Gln435 440 445Glu Gly Ala Arg Gln Lys Leu His Glu Leu Gln Glu Lys Leu Ser Pro450 455 460Leu Gly Glu Glu Met Arg Asp Arg Ala Arg Ala His Val Asp Ala Leu465 470 475 480Arg Thr His Leu Ala Pro Tyr Ser Asp Glu Leu Arg Gln Arg Leu Ala485 490 495Ala Arg Leu Glu Ala Leu Lys Glu Asn Gly Gly Ala Arg Leu Ala Glu500 505 510Tyr His Ala Lys Ala Thr Glu His Leu Ser Thr Leu Ser Glu Lys Ala515 520 525Lys Pro Ala Leu Glu Asp Leu Arg Gln Gly Leu Leu Pro Val Leu Glu530 535 540Ser Phe Lys Val Ser Phe Leu Ser Ala Leu Glu Glu Tyr Thr Lys Lys545 550 555 560Ieu Asn Thr Gln
<210>226<211>4458<212>DNA<213>Artificial Sequence<220>
<223>Apo43<400>226gaattcattg tactcccagt atcattatag tgaaagtttt ggctctctcg ccggtggttt 60tttacctcta tttaaagggg ttttccacct aaaaattctg gtatcattct cactttactt 120gttactttaa tttctcataa tctttggttg aaattatcac gcttccgcac acgatatccc 180tacaaattta ttatttgtta aacattttca aaccgcataa aattttatga agtcccgtct 240atctttaatg tagtctaaca ttttcatatt gaaatatata atttacttaa ttttagcgtt 300ggtagaaagc ataaagattt attcttattc ttcttcatat aaatgtttaa tatacaatat 360aaacaaattc tttaccttaa gaaggatttc ccattttata ttttaaaaat atatttatca 420aatatttttc aaccacgtaa atctcataat aataagttgt ttcaaaagta ataaaattta 480actccataat ttttttattc gactgatctt aaagcaacac ccagtgacac aactagccat 540ttttttcttt gaataaaaaa atccaattat cattgtattt tttttataca atgaaaattt 600caccaaacaa tcatttgtgg tatttctgaa gcaagtcatg ttatgcaaaa ttctataatt 660cccatttgac actacggaag taactgaaga tctgctttta catgcgagac acatcttcta 720aagtaatttt aataatagtt actatattca agatttcata tatcaaatac tcaatattac 780ttctaaaaaa ttaattagat ataattaaaa tattactttt ttaattttaa gtttaattgt 840tgaatttgtg actattgatt tattattcta ctatgtttaa attgttttat agatagttta 900aagtaaatat aagtaatgta gtagagtgtt agagtgttac cctaaaccat aaactataac 960atttatggtg gactaatttt catatatttc ttattgcttt taccttttct tggtatgtaa1020gtccgtaact agaattacag tgggttgcca tgacactctg tggtcttttg gttcatgcat1080gggtcttgcg caagaaaaag acaaagaaca aagaaaaaag acaaaacaga gagacaaaac1140gcaatcacac aaccaactca aattagtcac tggctgatca agatcgccgc gtccatgtat1200gtctaaatgc catgcaaagc aacacgtgct taacatgcac tttaaatggc tcacccatct1260caacccacac acaaacacat tgcctttttc ttcatcatca ccacaaccac ctgtatatat1320tcattctctt ccgccacctc aatttcttca cttcaacaca cgtcaacctg catatgcgtg1380tcatcccatg cccaaatctc catgcatgtt ccaaccacct tctctcttat ataataccta1440taaatacctc taatatcact cacttctttc atcatccatc catccagagt actactactc1500
tactactata ataccccaac ccaactcata ttcaatacta ctctaccatg aacttcctta1560agtctttccc tttctacgct ttcctttgtt tcggtcaata cttcgttgct gttacgcatg1620ctgacattgt gatgacacag tctccatcct ccctggctat gtcagtggga cagcgggtca1680ctatgcgctg caagtccagt cagagccttt taaaaagtac caatcaaaag aactatttgg1740cctggtacca gcagaaacca ggacagtctc ctaaacttct ggtatacttt gcatccacta1800gggaatctgg ggtccctgat cgcttcatag gcagtggatc tgggacagat ttcactctta1860ccatcagcag tgtgcaggct gaagacctgg cagattactt ctgtcagcaa cattataaca1920ctcctcccac gttcggtgct gggaccaagc tggagcttaa gcggtctccg aacggtgctt1980ctcatagcgg ttctgcacca ggcactagct ctgcatctgg atctcaggtg cacctgcagc2040agtctggagc tgagctgatg aagcctgggg cctcaatgaa gatatcctgc aaggctactg2100gctacacatt cagtagctac tggatagagt gggtaaagca gaggcctgga catggccttg2160agtggattgg agagatttta cctggcagtg gtagtactac ctacaatgag aagttcaagg2220gcaaggccac attcactgca gatacatcct ccaacacagc ctacatgcaa ctcagcagcc2280tgacatctga ggactctgcc gtctattact gtgcaagatt ggatgttgac tcctggggcc2340aaggcaccac tctcacagtc tcgactatgg ctgagatcac ccgcattcct ctctacaaag2400gtaagtctct ccgtaaggcg ctgaaggaac atggacttct agaagacttc ttgcagaaac2460aacagtatgg catctcgagc aagttcgatg aaccccccca gagcccctgg gatcgagtga2520aggacctggc cactgtgtac gtggatgtgc tcaaagacag cggcagagac tatgtgtccc2580agtttgaagg ctccgccttg ggaaaacagc taaacctaaa gctccttgac aactgggaca2640gcgtgacctc caccttcagc aagctgcgcg aacagctcgg ccctgtgacc caggagttct2700gggataacct ggaaaaggag acagagggcc tgaggcagga gatgagcaag gatctggagg2760aggtgaaggc caaggtgcag ccctacctgg acgacttcca gaagaagtgg caggaggaga2820tggagctcta ccgccagaag gtggagccgc tgcgcgcaga gctccaagag ggcgcgcgcc2880agaagctgca cgagctgcaa gagaagctga gcccactggg cgaggagatg cgcgaccgcg2940cgcgcgccca tgtggacgcg ctgcgcacgc atctggcccc ctacagcgac gagctgcgcc3000agcgcttggc cgcgcgcctt gaggctctca aggagaacgg cggcgccaga ctggccgagt3060accacgccaa ggccaccgag catctgagca cgctcagcga gaaggccaag cccgcgctag3120aggacctccg ccaaggcctg ctgcccgtgc tggagagctt caaggtcagc ttcctgagcg3180ctctggagga gtacactaag aagctcaaca cccagaaaga tgagctatga aagcttaaat3240
aagtatgaac taaaatgcat gtaggtgtaa gagctcatgg agagcatgga atattgtatc3300cgaccatgta acagtataat aactgagctc catctcactt cttctatgaa taaacaaagg3360atgttatgat atattaacac tctatctatg caccttattg ttctatgata aatttcctct3420tattattata aatcatctga atcgtgacgg cttatggaat gcttcaaata gtacaaaaac3480aaatgtgtac tataagactt tctaaacaat tctaacttta gcattgtgaa cgagacataa3540gtgttaagaa gacataacaa ttataatgga agaagtttgt ctccatttat atattatata3600ttacccactt atgtattata ttaggatgtt aaggagacat aacaattata aagagagaag3660tttgtatcca tttatatatt atatactacc catttatata ttatacttat ccacttattt3720aatgtcttta taaggtttga tccatgatat ttctaatatt ttagttgata tgtatatgaa3780aaggtactat ttgaactctc ttactctgta taaaggttgg atcatcctta aagtgggtct3840atttaatttt attgcttctt acagataaaa aaaaaattat gagttggttt gataaaatat3900tgaaggattt aaaataataa taaataataa ataacatata atatatgtat ataaatttat3960tataatataa catttatcta taaaaaagta aatattgtca taaatctata caatcgttta4020gccttgctgg aacgaatctc aattatttaa acgagagtaa acatatttga ctttttggtt4080atttaacaaa ttattattta acactatatg aaattttttt tttttatcag caaagaaata4140aaattaaatt aagaaggaca atggtgtgtc ccaatcctta tacaaccaac ttccacaaga4200aagtcaagtc agagacaaca aaaaaacaag caaaggaaat tttttaattt gagttgtctt4260gtttgctgca taatttatgc agtaaaacac tacacataac ccttttagca gtagagcaat4320ggttgaccgt gtgcttagct tcttttattt tattttttta tcagcaaaga ataaataaaa4380taaaatgaga cacttcaggg atgtttcaac ccttatacaa aaccccaaaa acaagtttcc4440tagcacccta ccaactaa 4458<210>227<211>560<212>PRT<213>Artificial Sequence<220>
<223>Apo43<400>227Met Asn Phe Leu Lys Ser Phe Pro Phe Tyr Ala Phe Leu Cys Phe Gly1 5 10 15Gln Tyr Phe Val Ala Val Thr His Ala Asp Ile Val Met Thr Gln Ser20 25 30
Pro Ser Ser Leu Ala Met Ser Val Gly Gln Arg Val Thr Met Arg Cys35 40 45Lys Ser Ser Gln Ser Leu Leu Lys Ser Thr Asn Gln Lys Asn Tyr Leu50 55 60Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Val Tyr65 70 75 80Phe Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ile Gly Ser85 90 95Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Val Gln Ala Glu100 105 110Asp Leu Ala Asp Tyr Phe Cys Gln Gln His Tyr Asn Thr Pro Pro Thr115 120 125Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys Arg Ser Pro Asn Gly Ala130 135 140Ser His Ser Gly Ser Ala Pro Gly Thr Ser Ser Ala Ser Gly Ser Gln145 150 155 160Val His Leu Gln Gln Ser Gly Ala Glu Leu Met Lys Pro Gly Ala Ser165 170 175Met Lys Ile Ser Cys Lys Ala Thr Gly Tyr Thr Phe Ser Ser Tyr Trp180 185 190Ile Glu Trp Val Lys Gln Arg Pro Gly His Gly Leu Glu Trp Ile Gly195 200 205Glu Ile Leu Pro Gly Ser Gly Ser Thr Thr Tyr Asn Glu Lys Phe Lys210 215 220Gly Lys Ala Thr Phe Thr Ala Asp Thr Ser Ser Asn Thr Ala Tyr Met225 230 235 240Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys Ala245 250 255Arg Leu Asp Val Asp Ser Trp Gly Gln Gly Thr Thr Leu Thr Val Ser
260 265 270Thr Met Ala Glu Ile Thr Arg Ile Pro Leu Tyr Lys Gly Lys Ser Leu275 280 285Arg Lys Ala Leu Lys Glu His Gly Leu Leu Glu Asp Phe Leu Gln Lys290 295 300Gln Gln Tyr Gly Ile Ser Ser Lys Phe Asp Glu Pro Pro Gln Ser Pro305 310 315 320Trp Asp Arg Val Lys Asp Leu Ala Thr Val Tyr Val Asp Val Leu Lys325 330 335Asp Ser Gly Arg Asp Tyr Val Ser Gln Phe Glu Gly Ser Ala Leu Gly340 345 350Lys Gln Leu Asn Leu Lys Leu Leu Asp Asn Trp Asp Ser Val Thr Ser355 360 365Thr Phe Ser Lys Leu Arg Glu Gln Leu Gly Pro Val Thr Gln Glu Phe370 375 380Trp Asp Asn Leu Glu Lys Glu Thr Glu Gly Leu Arg Gln Glu Met Ser385 390 395 400Lys Asp Leu Glu Glu Val Lys Ala Lys Val Gln Pro Tyr Leu Asp Asp405 410 415Phe Gln Lys Lys Trp Gln Glu Glu Met Glu Leu Tyr Arg Gln Lys Val420 425 430Glu Pro Leu Arg Ala Glu Leu Gln Glu Gly Ala Arg Gln Lys Leu His435 440 445Glu Leu Gln Glu Lys Leu Ser Pro Leu Gly Glu Glu Met Arg Asp Arg450 455 460Ala Arg Ala His Val Asp Ala Leu Arg Thr His Leu Ala Pro Tyr Ser465 470 475 480Asp Glu Leu Arg Gln Arg Leu Ala Ala Arg Leu Glu Ala Leu Lys Glu485 490 495
Asn Gly Gly Ala Arg Leu Ala Glu Tyr His Ala Lys Ala Thr Glu His500 505 510Leu Ser Thr Leu Ser Glu Lys Ala Lys Pro Ala Leu Glu Asp Leu Arg515 520 525Gln Gly Leu Leu Pro Val Leu Glu Ser Phe Lys Val Ser Phe Leu Ser530 535 540Ala Leu Glu Glu Tyr Thr Lys Lys Leu Asn Thr Gln Lys Asp Glu Leu545 550 555 560<210>228<211>4476<212>DNA<213>Artificial Sequence<220>
<223>Apo44<400>228gaattcattg tactcccagt atcattatag tgaaagtttt ggctctctcg ccggtggttt 60tttacctcta tttaaagggg ttttccacct aaaaattctg gtatcattct cactttactt 120gttactttaa tttctcataa tctttggttg aaattatcac gcttccgcac acgatatccc 180tacaaattta ttatttgtta aacattttca aaccgcataa aattttatga agtcccgtct 240atctttaatg tagtctaaca ttttcatatt gaaatatata atttacttaa ttttagcgtt 300ggtagaaagc ataaagattt attcttattc ttcttcatat aaatgtttaa tatacaatat 360aaacaaattc tttaccttaa gaaggatttc ccattttata ttttaaaaat atatttatca 420aatatttttc aaccacgtaa atctcataat aataagttgt ttcaaaagta ataaaattta 480actccataat ttttttattc gactgatctt aaagcaacac ccagtgacac aactagccat 540ttttttcttt gaataaaaaa atccaattat cattgtattt tttttataca atgaaaattt 600caccaaacaa tcatttgtgg tatttctgaa gcaagtcatg ttatgcaaaa ttctataatt 660cccatttgac actacggaag taactgaaga tctgctttta catgcgagac acatcttcta 720aagtaatttt aataatagtt actatattca agatttcata tatcaaatac tcaatattac 780ttctaaaaaa ttaattagat ataattaaaa tattactttt ttaattttaa gtttaattgt 840tgaatttgtg actattgatt tattattcta ctatgtttaa attgttttat agatagttta 900aagtaaatat aagtaatgta gtagagtgtt agagtgttac cctaaaccat aaactataac 960atttatggtg gactaatttt catatatttc ttattgcttt taccttttct tggtatgtaa1020
gtccgtaact agaattacag tgggttgcca tgacactctg tggtcttttg gttcatgcat1080gggtcttgcg caagaaaaag acaaagaaca aagaaaaaag acaaaacaga gagacaaaac1140gcaatcacac aaccaactca aattagtcac tggctgatca agatcgccgc gtccatgtat1200gtctaaatgc catgcaaagc aacacgtgct taacatgcac tttaaatggc tcacccatct1260caacccacac acaaacacat tgcctttttc ttcatcatca ccacaaccac ctgtatatat1320tcattctctt ccgccacctc aatttcttca cttcaacaca cgtcaacctg catatgcgtg1380tcatcccatg cccaaatctc catgcatgtt ccaaccacct tctctcttat ataataccta1440taaatacctc taatatcact cacttctttc atcatccatc catccagagt actactactc1500tactactata ataccccaac ccaactcata ttcaatacta ctctaccatg aacttcctta1560agtctttccc tttctacgct ttcctttgtt tcggtcaata cttcgttgct gttacgcatg1620ctgacattgt gatgacacag tctccatcct ccctggctat gtcagtggga cagcgggtca1680ctatgcgctg caagtccagt cagagccttt taaaaagtac caatcaaaag aactatttgg1740cctggtacca gcagaaacca ggacagtctc ctaaacttct ggtatacttt gcatccacta1800gggaatctgg ggtccctgat cgcttcatag gcagtggatc tgggacagat ttcactctta1860ccatcagcag tgtgcaggct gaagacctgg cagattactt ctgtcagcaa cattataaca1920ctcctcccac gttcggtgct gggaccaagc tggagcttaa gcggtctccg aacggtgctt1980ctcatagcgg ttctgcacca ggcactagct ctgcatctgg atctcaggtg cacctgcagc2040agtctggagc tgagctgatg aagcctgggg cctcaatgaa gatatcctgc aaggctactg2100gctacacatt cagtagctac tggatagagt gggtaaagca gaggcctgga catggccttg2160agtggattgg agagatttta cctggcagtg gtagtactac ctacaatgag aagttcaagg2220gcaaggccac attcactgca gatacatcct ccaacacagc ctacatgcaa ctcagcagcc2280tgacatctga ggactctgcc gtctattact gtgcaagatt ggatgttgac tcctggggcc2340aaggcaccac tctcacagtc tcgactatgg ctgagatcac ccgcattcct ctctacaaag2400gtaagtctct ccgtaaggcg ctgaaggaac atggacttct agaagacttc ttgcagaaac2460aacagtatgg catctcgagc aagttccggc atttctggca gcaagatgaa cccccccaga2520gcccctggga tcgagtgaag gacctggcca ctgtgtacgt ggatgtgctc aaagacagcg2580gcagagacta tgtgtcccag tttgaaggct ccgccttggg aaaacagcta aacctaaagc2640tccttgacaa ctgggacagc gtgacctcca ccttcagcaa gctgcgcgaa cagctcggcc2700ctgtgaccca ggagttctgg gataacctgg aaaaggagac agagggcctg aggcaggaga2760tgagcaagga tctggaggag gtgaaggcca aggtgcagcc ctacctggac gacttccaga2820
agaagtggca ggaggagatg gagctctacc gccagaaggt ggagccgctg cgcgcagagc2880tccaagaggg cgcgcgccag aagctgcacg agctgcaaga gaagctgagc ccactgggcg2940aggagatgcg cgaccgcgcg cgcgcccatg tggacgcgct gcgcacgcat ctggccccct3000acagcgacga gctgcgccag cgcttggccg cgcgccttga ggctctcaag gagaacggcg3060gcgccagact ggccgagtac cacgccaagg ccaccgagca tctgagcacg ctcagcgaga3120aggccaagcc cgcgctagag gacctccgcc aaggcctgct gcccgtgctg gagagcttca3180aggtcagctt cctgagcgct ctggaggagt acactaagaa gctcaacacc cagaaagatg3240agctatgaaa gcttaaataa gtatgaacta aaatgcatgt aggtgtaaga gctcatggag3300agcatggaat attgtatccg accatgtaac agtataataa ctgagctcca tctcacttct3360tctatgaata aacaaaggat gttatgatat attaacactc tatctatgca ccttattgtt3420ctatgataaa tttcctctta ttattataaa tcatctgaat cgtgacggct tatggaatgc3480ttcaaatagt acaaaaacaa atgtgtacta taagactttc taaacaattc taactttagc3540attgtgaacg agacataagt gttaagaaga cataacaatt ataatggaag aagtttgtct3600ccatttatat attatatatt acccacttat gtattatatt aggatgttaa ggagacataa3660caattataaa gagagaagtt tgtatccatt tatatattat atactaccca tttatatatt3720atacttatcc acttatttaa tgtctttata aggtttgatc catgatattt ctaatatttt3780agttgatatg tatatgaaaa ggtactattt gaactctctt actctgtata aaggttggat3840catccttaaa gtgggtctat ttaattttat tgcttcttac agataaaaaa aaaattatga3900gttggtttga taaaatattg aaggatttaa aataataata aataataaat aacatataat3960atatgtatat aaatttatta taatataaca tttatctata aaaaagtaaa tattgtcata4020aatctataca atcgtttagc cttgctggaa cgaatctcaa ttatttaaac gagagtaaac4080atatttgact ttttggttat ttaacaaatt attatttaac actatatgaa attttttttt4140tttatcagca aagaaataaa attaaattaa gaaggacaat ggtgtgtccc aatccttata4200caaccaactt ccacaagaaa gtcaagtcag agacaacaaa aaaacaagca aaggaaattt4260tttaatttga gttgtcttgt ttgctgcata atttatgcag taaaacacta cacataaccc4320ttttagcagt agagcaatgg ttgaccgtgt gcttagcttc ttttatttta tttttttatc4380agcaaagaat aaataaaata aaatgagaca cttcagggat gtttcaaccc ttatacaaaa4440ccccaaaaac aagtttccta gcaccctacc aactaa 4476<210>229
<211>566<212>PRT<213>Artificial Sequence<220>
<223>Apo44<400>229Met Asn Phe Leu Lys Ser Phe Pro Phe Tyr Ala Phe Leu Cys Phe Gly1 5 10 15Gln Tyr Phe Val Ala Val Thr His Ala Asp Ile Val Met Thr Gln Ser20 25 30Pro Ser Ser Leu Ala Met Ser Val Gly Gln Arg Val Thr Met Arg Cys35 40 45Lys Ser Ser Gln Ser Leu Leu Lys Ser Thr Asn Gln Lys Asn Tyr Leu50 55 60Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Val Tyr65 70 75 80Phe Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ile Gly Ser85 90 95Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Val Gln Ala Glu100 105 110Asp Leu Ala Asp Tyr Phe Cys Gln Gln His Tyr Asn Thr Pro Pro Thr115 120 125Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys Arg Ser Pro Asn Gly Ala130 135 140Ser His Ser Gly Ser Ala Pro Gly Thr Ser Ser Ala Ser Gly Ser Gln145 150 155 160Val His Leu Gln Gln Ser Gly Ala Glu Leu Met Lys Pro Gly Ala Ser165 170 175Met Lys Ile Ser Cys Lys Ala Thr Gly Tyr Thr Phe Ser Ser Tyr Trp180 185 190Ile Glu Trp Val Lys Gln Arg Pro Gly His Gly Leu Glu Trp Ile Gly195 200 205
Glu Ile Leu Pro Gly Ser Gly Ser Thr Thr Tyr Asn Glu Lys Phe Lys210 215 220Gly Lys Ala Thr Phe Thr Ala Asp Thr Ser Ser Asn Thr Ala Tyr Met225 230 235 240Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys Ala245 250 255Arg Leu Asp Val Asp Ser Trp Gly Gln Gly Thr Thr Leu Thr Val Ser260 265 270Thr Met Ala Glu Ile Thr Arg Ile Pro Leu Tyr Lys Gly Lys Ser Leu275 280 285Arg Lys Ala Leu Lys Glu His Gly Leu Leu Glu Asp Phe Leu Gln Lys290 295 300Gln Gln Tyr Gly Ile Ser Ser Lys Phe Arg His Phe Trp Gln Gln Asp305 310 315 320Glu Pro Pro Gln Ser Pro Trp Asp Arg Val Lys Asp Leu Ala Thr Val325 330 335Tyr Val Asp Val Leu Lys Asp Ser Gly Arg Asp Tyr Val Ser Gln Phe340 345 350Glu Gly Ser Ala Leu Gly Lys Gln Leu Asn Leu Lys Leu Leu Asp Asn355 360 365Trp Asp Ser Val Thr Ser Thr Phe Ser Lys Leu Arg Glu Gln Leu Gly370 375 380Pro Val Thr Gln Glu Phe Trp Asp Asn Leu Glu Lys Glu Thr Glu Gly385 390 395 400Leu Arg Gln Glu Met Ser Lys Asp Leu Glu Glu Val Lys Ala Lys Val405 410 415Gln Pro Tyr Leu Asp Asp Phe Gln Lys Lys Trp Gln Glu Glu Met Glu420 425 430Leu Tyr Arg Gln Lys Val Glu Pro Leu Arg Ala Glu Leu Gln Glu Gly
435 440 445Ala Arg Gln Lys Leu His Glu Leu Gln Glu Lys Leu Ser Pro Leu Gly450 455 460Glu Glu Met Arg Asp Arg Ala Arg Ala His Val Asp Ala Leu Arg Thr465 470 475 480His Leu Ala Pro Tyr Ser Asp Glu Leu Arg Gln Arg Leu Ala Ala Arg485 490 495Leu Glu Ala Leu Lys Glu Asn Gly Gly Ala Arg Leu Ala Glu Tyr His500 505 510Ala Lys Ala Thr Glu His Leu Ser Thr Leu Ser Glu Lys Ala Lys Pro515 520 525Ala Leu Glu Asp Leu Arg Gln Gly Leu Leu Pro Val Leu Glu Ser Phe530 535 540Lys Val Ser Phe Leu Ser Ala Leu Glu Glu Tyr Thr Lys Lys Leu Asn545 550 555 560Thr Gln Lys Asp Glu Leu565<210>230<211>4461<212>DNA<213>Artificial Sequence<220>
<223>Apo45<400>230gaattcattg tactcccagt atcattatag tgaaagtttt ggctctctcg ccggtggttt 60tttacctcta tttaaagggg ttttccacct aaaaattctg gtatcattct cactttactt120gttactttaa tttctcataa tctttggttg aaattatcac gcttccgcac acgatatccc180tacaaattta ttatttgtta aacattttca aaccgcataa aattttatga agtcccgtct240atctttaatg tagtctaaca ttttcatatt gaaatatata atttacttaa ttttagcgtt300ggtagaaagc ataaagattt attcttattc ttcttcatat aaatgtttaa tatacaatat360aaacaaattc tttaccttaa gaaggatttc ccattttata ttttaaaaat atatttatca420aatatttttc aaccacgtaa atctcataat aataagttgt ttcaaaagta ataaaattta480
actccataat ttttttattc gactgatctt aaagcaacac ccagtgacac aactagccat 540ttttttcttt gaataaaaaa atccaattat cattgtattt tttttataca atgaaaattt 600caccaaacaa tcatttgtgg tatttctgaa gcaagtcatg ttatgcaaaa ttctataatt 660cccatttgac actacggaag taactgaaga tctgctttta catgcgagac acatcttcta 720aagtaatttt aataatagtt actatattca agatttcata tatcaaatac tcaatattac 780ttctaaaaaa ttaattagat ataattaaaa tattactttt ttaattttaa gtttaattgt 840tgaatttgtg actattgatt tattattcta ctatgtttaa attgttttat agatagttta 900aagtaaatat aagtaatgta gtagagtgtt agagtgttac cctaaaccat aaactataac 960atttatggtg gactaatttt catatatttc ttattgcttt taccttttct tggtatgtaa1020gtccgtaact agaattacag tgggttgcca tgacactctg tggtcttttg gttcatgcat1080gggtcttgcg caagaaaaag acaaagaaca aagaaaaaag acaaaacaga gagacaaaac1140gcaatcacac aaccaactca aattagtcac tggctgatca agatcgccgc gtccatgtat1200gtctaaatgc catgcaaagc aacacgtgct taacatgcac tttaaatggc tcacccatct1260caacccacac acaaacacat tgcctttttc ttcatcatca ccacaaccac ctgtatatat1320tcattctctt ccgccacctc aatttcttca cttcaacaca cgtcaacctg catatgcgtg1380tcatcccatg cccaaatctc catgcatgtt ccaaccacct tctctcttat ataataccta1440taaatacctc taatatcact cacttctttc atcatccatc catccagagt actactactc1500tactactata ataccccaac ccaactcata ttcaatacta ctctaccatg aacttcctta1560agtctttccc tttctacgct ttcctttgtt tcggtcaata cttcgttgct gttacgcatg1620ctgacattgt gatgacacag tctccatcct ccctggctat gtcagtggga cagcgggtca1680ctatgcgctg caagtccagt cagagccttt taaaaagtac caatcaaaag aactatttgg1740cctggtacca gcagaaacca ggacagtctc ctaaacttct ggtatacttt gcatccacta1800gggaatctgg ggtccctgat cgcttcatag gcagtggatc tgggacagat ttcactctta1860ccatcagcag tgtgcaggct gaagacctgg cagattactt ctgtcagcaa cattataaca1920ctcctcccac gttcggtgct gggaccaagc tggagcttaa gcggtctccg aacggtgctt1980ctcatagcgg ttctgcacca ggcactagct ctgcatctgg atctcaggtg cacctgcagc2040agtctggagc tgagctgatg aagcctgggg cctcaatgaa gatatcctgc aaggctactg2100gctacacatt cagtagctac tggatagagt gggtaaagca gaggcctgga catggccttg2160agtggattgg agagatttta cctggcagtg gtagtactac ctacaatgag aagttcaagg2220
gcaaggccac attcactgca gatacatcct ccaacacagc ctacatgcaa ctcagcagcc2280tgacatctga ggactctgcc gtctattact gtgcaagatt ggatgttgac tcctggggcc2340aaggcaccac tctcacagtc tcgactatgg ctgagatcac ccgcattcct ctctacaaag2400gtaagtctct ccgtaaggcg ctgaaggaac atggacttct agaagacttc ttgcagaaac2460aacagtatgg catctcgagc aagttcatgg atgaaccccc ccagagcccc tgggatcgag2520tgaaggacct ggccactgtg tacgtggatg tgctcaaaga cagcggcaga gactatgtgt2580cccagtttga aggctccgcc ttgggaaaac agctaaacct aaagctcctt gacaactggg2640acagcgtgac ctccaccttc agcaagctgc gcgaacagct cggccctgtg acccaggagt2700tctgggataa cctggaaaag gagacagagg gcctgaggca ggagatgagc aaggatctgg2760aggaggtgaa ggccaaggtg cagccctacc tggacgactt ccagaagaag tggcaggagg2820agatggagct ctaccgccag aaggtggagc cgctgcgcgc agagctccaa gagggcgcgc2880gccagaagct gcacgagctg caagagaagc tgagcccact gggcgaggag atgcgcgacc2940gcgcgcgcgc ccatgtggac gcgctgcgca cgcatctggc cccctacagc gacgagctgc3000gccagcgctt ggccgcgcgc cttgaggctc tcaaggagaa cggcggcgcc agactggccg3060agtaccacgc caaggccacc gagcatctga gcacgctcag cgagaaggcc aagcccgcgc3120tcgaggacct ccgccaaggc ctgctgcccg tgctggagag cttcaaggtc agcttcctga3180gcgctctcga ggagtacact aagaagctca acacccagaa agatgagcta tgaaagctta3240aataagtatg aactaaaatg catgtaggtg taagagctca tggagagcat ggaatattgt3300atccgaccat gtaacagtat aataactgag ctccatctca cttcttctat gaataaacaa3360aggatgttat gatatattaa cactctatct atgcacctta ttgttctatg ataaatttcc3420tcttattatt ataaatcatc tgaatcgtga cggcttatgg aatgcttcaa atagtacaaa3480aacaaatgtg tactataaga ctttctaaac aattctaact ttagcattgt gaacgagaca3540taagtgttaa gaagacataa caattataat ggaagaagtt tgtctccatt tatatattat3600atattaccca cttatgtatt atattaggat gttaaggaga cataacaatt ataaagagag3660aagtttgtat ccatttatat attatatact acccatttat atattatact tatccactta3720tttaatgtct ttataaggtt tgatccatga tatttctaat attttagttg atatgtatat3780gaaaaggtac tatttgaact ctcttactct gtataaaggt tggatcatcc ttaaagtggg3840tctatttaat tttattgctt cttacagata aaaaaaaaat tatgagttgg tttgataaaa3900tattgaagga tttaaaataa taataaataa taaataacat ataatatatg tatataaatt3960tattataata taacatttat ctataaaaaa gtaaatattg tcataaatct atacaatcgt4020
ttagccttgc tggaacgaat ctcaattatt taaacgagag taaacatatt tgactttttg4080gttatttaac aaattattat ttaacactat atgaaatttt ttttttttat cagcaaagaa4140ataaaattaa attaagaagg acaatggtgt gtcccaatcc ttatacaacc aacttccaca4200agaaagtcaa gtcagagaca acaaaaaaac aagcaaagga aattttttaa tttgagttgt4260cttgtttgct gcataattta tgcagtaaaa cactacacat aaccctttta gcagtagagc4320aatggttgac cgtgtgctta gcttctttta ttttattttt ttatcagcaa agaataaata4380aaataaaatg agacacttca gggatgtttc aacccttata caaaacccca aaaacaagtt4440tcctagcacc ctaccaacta a 4461<210>231<211>561<212>PRT<213>Artificial Sequence<220>
<223>Apo45<400>231Met Asn Phe Leu Lys Ser Phe Pro Phe Tyr Ala Phe Leu Cys Phe Gly1 5 10 15Gln Tyr Phe Val Ala Val Thr His Ala Asp Ile Val Met Thr Gln Ser20 25 30Pro Ser Ser Leu Ala Met Ser Val Gly Gln Arg Val Thr Met Arg Cys35 40 45Lys Ser Ser Gln Ser Leu Leu Lys Ser Thr Asn Gln Lys Asn Tyr Leu50 55 60Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Val Tyr65 70 75 80Phe Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ile Gly Ser85 90 95Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Val Gln Ala Glu100 105 110Asp Leu Ala Asp Tyr Phe Cys Gln Gln His Tyr Asn Thr Pro Pro Thr115 120 125
Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys Arg Ser Pro Asn Gly Ala130 135 140Ser His Ser Gly Ser Ala Pro Gly Thr Ser Ser Ala Ser Gly Ser Gln145 150 155 160Val His Leu Gln Gln Ser Gly Ala Glu Leu Met Lys Pro Gly Ala Ser165 170 175Met Lys Ile Ser Cys Lys Ala Thr Gly Tyr Thr Phe Ser Ser Tyr Trp180 185 190Ile Glu Trp Val Lys Gln Arg Pro Gly His Gly Leu Glu Trp Ile Gly195 200 205Glu Ile Leu Pro Gly Ser Gly Ser Thr Thr Tyr Asn Glu Lys Phe Lys210 215 220Gly Lys Ala Thr Phe Thr Ala Asp Thr Ser Ser Asn Thr Ala Tyr Met225 230 235 240Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys Ala245 250 255Arg Leu Asp Val Asp Ser Trp Gly Gln Gly Thr Thr Leu Thr Val Ser260 265 270Thr Met Ala Glu Ile Thr Arg Ile Pro Leu Tyr Lys Gly Lys Ser Leu275 280 285Arg Lys Ala Leu Lys Glu His Gly Leu Leu Glu Asp Phe Leu Gln Lys290 295 300Gln Gln Tyr Gly Ile Ser Ser Lys Phe Met Asp Glu Pro Pro Gln Ser305 310 315 320Pro Trp Asp Arg Val Lys Asp Leu Ala Thr Val Tyr Val Asp Val Leu325 330 335Lys Asp Ser Gly Arg Asp Tyr Val Ser Gln Phe Glu Gly Ser Ala Leu340 345 350Gly Lys Gln Leu Asn Leu Lys Leu Leu Asp Asn Trp Asp Ser Val Thr355 360 365
Ser Thr Phe Ser Lys Leu Arg Glu Gln Leu Gly Pro Val Thr Gln Glu370 375 380Phe Trp Asp Asn Leu Glu Lys Glu Thr Glu Gly Leu Arg Gln Glu Met385 390 395 400Ser Lys Asp Leu Glu Glu Val Lys Ala Lys Val Gln Pro Tyr Leu Asp405 410 415Asp Phe Gln Lys Lys Trp Gln Glu Glu Met Glu Leu Tyr Arg Gln Lys420 425 430Val Glu Pro Leu Arg Ala Glu Leu Gln Glu Gly Ala Arg Gln Lys Leu435 440 445His Glu Leu Gln Glu Lys Leu Ser Pro Leu Gly Glu Glu Met Arg Asp450 455 460Arg Ala Arg Ala His Val Asp Ala Leu Arg Thr His Leu Ala Pro Tyr465 470 475 480Ser Asp Glu Leu Arg Gln Arg Leu Ala Ala Arg Leu Glu Ala Leu Lys485 490 495Glu Asn Gly Gly Ala Arg Leu Ala Glu Tyr His Ala Lys Ala Thr Glu500 505 510His Leu Ser Thr Leu Ser Glu Lys Ala Lys Pro Ala Leu Glu Asp Leu515 520 525Arg Gln Gly Leu Leu Pro Val Leu Glu Ser Phe Lys Val Ser Phe Leu530 535 540Ser Ala Leu Glu Glu Tyr Thr Lys Lys Leu Asn Thr Gln Lys Asp Glu545 550 555 560Leu<210>232<211>4482<212>DNA<213>Artificial Sequence
<220>
<223>Apo46<400>232gaattcattg tactcccagt atcattatag tgaaagtttt ggctctctcg ccggtggttt 60tttacctcta tttaaagggg ttttccacct aaaaattctg gtatcattct cactttactt 120gttactttaa tttctcataa tctttggttg aaattatcac gcttccgcac acgatatccc 180tacaaattta ttatttgtta aacattttca aaccgcataa aattttatga agtcccgtct 240atctttaatg tagtctaaca ttttcatatt gaaatatata atttacttaa ttttagcgtt 300ggtagaaagc ataaagattt attcttattc ttcttcatat aaatgtttaa tatacaatat 360aaacaaattc tttaccttaa gaaggatttc ccattttata ttttaaaaat atatttatca 420aatatttttc aaccacgtaa atctcataat aataagttgt ttcaaaagta ataaaattta 480actccataat ttttttattc gactgatctt aaagcaacac ccagtgacac aactagccat 540ttttttcttt gaataaaaaa atccaattat cattgtattt tttttataca atgaaaattt 600caccaaacaa tcatttgtgg tatttctgaa gcaagtcatg ttatgcaaaa ttctataatt 660cccatttgac actacggaag taactgaaga tctgctttta catgcgagac acatcttcta 720aagtaatttt aataatagtt actatattca agatttcata tatcaaatac tcaatattac 780ttctaaaaaa ttaattagat ataattaaaa tattactttt ttaattttaa gtttaattgt 840tgaatttgtg actattgatt tattattcta ctatgtttaa attgttttat agatagttta 900aagtaaatat aagtaatgta gtagagtgtt agagtgttac cctaaaccat aaactataac 960atttatggtg gactaatttt catatatttc ttattgcttt taccttttct tggtatgtaa1020gtccgtaact agaattacag tgggttgcca tgacactctg tggtcttttg gttcatgcat1080gggtcttgcg caagaaaaag acaaagaaca aagaaaaaag acaaaacaga gagacaaaac1140gcaatcacac aaccaactca aattagtcac tggctgatca agatcgccgc gtccatgtat1200gtctaaatgc catgcaaagc aacacgtgct taacatgcac tttaaatggc tcacccatct1260caacccacac acaaacacat tgcctttttc ttcatcatca ccacaaccac ctgtatatat1320tcattctctt ccgccacctc aatttcttca cttcaacaca cgtcaacctg catatgcgtg1380tcatcccatg cccaaatctc catgcatgtt ccaaccacct tctctcttat ataataccta1440taaatacctc taatatcact cacttctttc atcatccatc catccagagt actactactc1500tactactata ataccccaac ccaactcata ttcaatacta ctctaccatg aacttcctta1560agtctttccc tttctacgct ttcctttgtt tcggtcaata cttcgttgct gttacgcatg1620ctgacattgt gatgacacag tctccatcct ccctggctat gtcagtggga cagcgggtca1680
ctatgcgctg caagtccagt cagagccttt taaaaagtac caatcaaaag aactatttgg1740cctggtacca gcagaaacca ggacagtctc ctaaacttct ggtatacttt gcatccacta1800gggaatctgg ggtccctgat cgcttcatag gcagtggatc tgggacagat ttcactctta1860ccatcagcag tgtgcaggct gaagacctgg cagattactt ctgtcagcaa cattataaca1920ctcctcccac gttcggtgct gggaccaagc tggagcttaa gcggtctccg aacggtgctt1980ctcatagcgg ttctgcacca ggcactagct ctgcatctgg atctcaggtg cacctgcagc2040agtctggagc tgagctgatg aagcctgggg cctcaatgaa gatatcctgc aaggctactg2100gctacacatt cagtagctac tggatagagt gggtaaagca gaggcctgga catggccttg2160agtggattgg agagatttta cctggcagtg gtagtactac ctacaatgag aagttcaagg2220gcaaggccac attcactgca gatacatcct ccaacacagc ctacatgcaa ctcagcagcc2280tgacatctga ggactctgcc gtctattact gtgcaagatt ggatgttgac tcctggggcc2340aaggcaccac tctcacagtc tcgactatgg ctgagatcac ccgcattcct ctctacaaag2400gtaagtctct ccgtaaggcg ctgaaggaac atggacttct agaagacttc ttgcagaaac2460aacagtatgg catctcgagc aagttcatgg ggcggcattt ctggcagcaa gatgaacccc2520cccagagccc ctgggatcga gtgaaggacc tggccactgt gtacgtggat gtgctcaaag2580acagcggcag agactatgtg tcccagtttg aaggctccgc cttgggaaaa cagctaaacc2640taaagctcct tgacaactgg gacagcgtga cctccacctt cagcaagctg cgcgaacagc2700tcggccctgt gacccaggag ttctgggata acctggaaaa ggagacagag ggcctgaggc2760aggagatgag caaggatctg gaggaggtga aggccaaggt gcagccctac ctggacgact2820tccagaagaa gtggcaggag gagatggagc tctaccgcca gaaggtggag ccgctgcgcg2880cagagctcca agagggcgcg cgccagaagc tgcacgagct gcaagagaag ctgagcccac2940tgggcgagga gatgcgcgac cgcgcgcgcg cccatgtgga cgcgctgcgc acgcatctgg3000ccccctacag cgacgagctg cgccagcgct tggccgcgcg ccttgaggct ctcaaggaga3060acggcggcgc cagactggcc gagtaccacg ccaaggccac cgagcatctg agcacgctca3120gcgagaaggc caagcccgcg ctcgaggacc tccgccaagg cctgctgccc gtgctggaga3180gcttcaaggt cagcttcctg agcgctctcg aggagtacac taagaagctc aacacccaga3240aagatgagct atgaaagctt aaataagtat gaactaaaat gcatgtaggt gtaagagctc3300atggagagca tggaatattg tatccgacca tgtaacagta taataactga gctccatctc3360acttcttcta tgaataaaca aaggatgtta tgatatatta acactctatc tatgcacctt3420
attgttctat gataaatttc ctcttattat tataaatcat ctgaatcgtg acggcttatg3480gaatgcttca aatagtacaa aaacaaatgt gtactataag actttctaaa caattctaac3540tttagcattg tgaacgagac ataagtgtta agaagacata acaattataa tggaagaagt3600ttgtctccat ttatatatta tatattaccc acttatgtat tatattagga tgttaaggag3660acataacaat tataaagaga gaagtttgta tccatttata tattatatac tacccattta3720tatattatac ttatccactt atttaatgtc tttataaggt ttgatccatg atatttctaa3780tattttagtt gatatgtata tgaaaaggta ctatttgaac tctcttactc tgtataaagg3840ttggatcatc cttaaagtgg gtctatttaa ttttattgct tcttacagat aaaaaaaaaa3900ttatgagttg gtttgataaa atattgaagg atttaaaata ataataaata ataaataaca3960tataatatat gtatataaat ttattataat ataacattta tctataaaaa agtaaatatt4020gtcataaatc tatacaatcg tttagccttg ctggaacgaa tctcaattat ttaaacgaga4080gtaaacatat ttgacttttt ggttatttaa caaattatta tttaacacta tatgaaattt4140ttttttttta tcagcaaaga aataaaatta aattaagaag gacaatggtg tgtcccaatc4200cttatacaac caacttccac aagaaagtca agtcagagac aacaaaaaaa caagcaaagg4260aaatttttta atttgagttg tcttgtttgc tgcataattt atgcagtaaa acactacaca4320taaccctttt agcagtagag caatggttga ccgtgtgctt agcttctttt attttatttt4380tttatcagca aagaataaat aaaataaaat gagacacttc agggatgttt caacccttat4440acaaaacccc aaaaacaagt ttcctagcac cctaccaact aa 4482<210>233<211>568<212>PRT<213>Artificial Sequence<220>
<223>Apo46<400>233Met Asn Phe Leu Lys Ser Phe Pro Phe Tyr Ala Phe Leu Cys Phe Gly1 5 10 15Gln Tyr Phe Val Ala Val Thr His Ala Asp Ile Val Met Thr Gln Ser20 25 30Pro Ser Ser Leu Ala Met Ser Val Gly Gln Arg Val Thr Met Arg Cys35 40 45
Lys Ser Ser Gln Ser Leu Leu Lys Ser Thr Asn Gln Lys Asn Tyr Leu50 55 60Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Val Tyr65 70 75 80Phe Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ile Gly Ser85 90 95Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Val Gln Ala Glu100 105 110Asp Leu Ala Asp Tyr Phe Cys Gln Gln His Tyr Asn Thr Pro Pro Thr115 120 125Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys Arg Ser Pro Asn Gly Ala130 135 140Ser His Ser Gly Ser Ala Pro Gly Thr Ser Ser Ala Ser Gly Ser Gln145 150 155 160Val His Leu Gln Gln Ser Gly Ala Glu Leu Met Lys Pro Gly Ala Ser165 170 175Met Lys Ile Ser Cys Lys Ala Thr Gly Tyr Thr Phe Ser Ser Tyr Trp180 185 190Ile Glu Trp Val Lys Gln Arg Pro Gly His Gly Leu Glu Trp Ile Gly195 200 205Glu Ile Leu Pro Gly Ser Gly Ser Thr Thr Tyr Asn Glu Lys Phe Lys210 215 220Gly Lys Ala Thr Phe Thr Ala Asp Thr Ser Ser Asn Thr Ala Tyr Met225 230 235 240Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys Ala245 250 255Arg Leu Asp Val Asp Ser Trp Gly Gln Gly Thr Thr Leu Thr Val Ser260 265 270Thr Met Ala Glu Ile Thr Arg Ile Pro Leu Tyr Lys Gly Lys Ser Leu275 280 285
Arg Lys Ala Leu Lys Glu His Gly Leu Leu Glu Asp Phe Leu Gln Lys290 295 300Gln Gln Tyr Gly Ile Ser Ser Lys Phe Met Gly Arg His Phe Trp Gln305 310 315 320Gln Asp Glu Pro Pro Gln Ser Pro Trp Asp Arg Val Lys Asp Leu Ala325 330 335Thr Val Tyr Val Asp Val Leu Lys Asp Ser Gly Arg Asp Tyr Val Ser340 345 350Gln Phe Glu Gly Ser Ala Leu Gly Lys Gln Leu Asn Leu Lys Leu Leu355 360 365Asp Asn Trp Asp Ser Val Thr Ser Thr Phe Ser Lys Leu Arg Glu Gln370 375 380Leu Gly Pro Val Thr Gln Glu Phe Trp Asp Asn Leu Glu Lys Glu Thr385 390 395 400Glu Gly Leu Arg Gln Glu Met Ser Lys Asp Leu Glu Glu Val Lys Ala405 410 415Lys Val Gln Pro Tyr Leu Asp Asp Phe Gln Lys Lys Trp Gln Glu Glu420 425 430Met Glu Leu Tyr Arg Gln Lys Val Glu Pro Leu Arg Ala Glu Leu Gln435 440 445Glu Gly Ala Arg Gln Lys Leu His Glu Leu Gln Glu Lys Leu Ser Pro450 455 460Leu Gly Glu Glu Met Arg Asp Arg Ala Arg Ala His Val Asp Ala Leu465 470 475 480Arg Thr His Leu Ala Pro Tyr Ser Asp Glu Leu Arg Gln Arg Leu Ala485 490 495Ala Arg Leu Glu Ala Leu Lys Glu Asn Gly Gly Ala Arg Leu Ala Glu500 505 510Tyr His Ala Lys Ala Thr Glu His Leu Ser Thr Leu Ser Glu Lys Ala515 520 525
Lys Pro Ala Leu Glu Asp Leu Arg Gln Gly Leu Leu Pro Val Leu Glu530 535 540Ser Phe Lys Val Ser Phe Leu Ser Ala Leu Glu Glu Tyr Thr Lys Lys545 550 555 560Leu Asn Thr Gln Lys Asp Glu Leu565<210>234<211>1329<212>DNA<213>Artificial Sequence<220>
<223>Apo47<400>234atggctgatc accaccgggg tgcgacggga ggtggcgggg gctacggcga cctccagcgc 60gggggcggca tgcacggcga ggcgcagcag cagcagaagc agggcgccat gatgacggcg 120ctcaaggccg cgacggccgc gaccttcggc gggtcgatgc tggtgctgtc cgggctgatc 180ctggccggca ccgtgatcgc gctcacggtg gccacccccg tgctggtgat cttcagcccg 240gtgctggtgc cggccgceat cgcgctggcg ctcatggcgg ccgggttcgt cacctccggc 300ggcctcggcg tcgctgcgct gtccgtgttc tcctggatgt acaagtacct gacgggcaag 360cacccgccgg gcgccgacca gctggaccac gccaaggcga ggctggcgtc caaggcccgc 420gacatcaagg atgcagcaca gcaccgcatc gaccaggcgc aggggtctaa gcttatggct 480gagatcaccc gcattcctct ctacaaaggt aagtctctcc gtaaggcgct gaaggaacat 540ggacttctag aagacttctt gcagaaacaa cagtatggca tctcgagcaa gttcatggat 600gaaccccccc agagcccctg ggatcgagtg aaggacctgg ccactgtgta cgtggatgtg 660ctcaaagaca gcggcagaga ctatgtgtcc cagtttgaag gctccgcctt gggaaaacag 720ctaaacctaa agctccttga caactgggac agcgtgacct ccaccttcag caagctgcgc 780gaacagctcg gccctgtgac ccaggagttc tgggataacc tggaaaagga gacagagggc 840ctgaggcagg agatgagcaa ggatctggag gaggtgaagg ccaaggtgca gccctacctg 900gacgacttcc agaagaagtg gcaggaggag atggagctct accgccagaa ggtggagccg 960ctgcgcgcag agctccaaga gggcgcgcgc cagaagctgc acgagctgca agagaagctg1020agcccactgg gcgaggagat gcgcgaccgc gcgcgcgccc atgtggacgc gctgcgcacg1080
catctggccc cctacagcga cgagctgcgc cagcgcttgg ccgcgcgcct tgaggctctc1140aaggagaacg gcggcgccag actggccgag taccacgcca aggccaccga gcatctgagc1200acgctcagcg agaaggccaa gcccgcgctc gaggacctcc gccaaggcct gctgcccgtg1260ctggagagct tcaaggtcag cttcctgagc gctctcgagg agtacactaa gaagctcaac1320acccagtga1329<210>235<211>442<212>PRT<213>Artificial Sequence<220>
<223>Apo47<400>235Met Ala Asp His His Arg Gly Ala Thr Gly Gly Gly Gly Gly Tyr Gly1 5 10 15Asp Leu Gln Arg Gly Gly Gly Met His Gly Glu Ala Gln Gln Gln Gln20 25 30Lys Gln Gly Ala Met Met Thr Ala Leu Lys Ala Ala Thr Ala Ala Thr35 40 45Phe Gly Gly Ser Met Leu Val Leu Ser Gly Leu Ile Leu Ala Gly Thr50 55 60Val Ile Ala Leu Thr Val Ala Thr Pro Val Leu Val Ile Phe Ser Pro65 70 75 80Val Leu Val Pro Ala Ala Ile Ala Leu Ala Leu Met Ala Ala Gly Phe85 90 95Val Thr Ser Gly Gly Leu Gly Val Ala Ala Leu Ser Val Phe Ser Trp100 105 110Met Tyr Lys Tyr Leu Thr Gly Lys His Pro Pro Gly Ala Asp Gln Leu115 120 125Asp His Ala Lys Ala Arg Leu Ala Ser Lys Ala Arg Asp Ile Lys Asp130 135 140Ala Ala Gln His Arg Ile Asp Gln Ala Gln Gly Ser Lys Leu Met Ala145 150 155 160
Glu Ile Thr Arg Ile Pro Leu Tyr Lys Gly Lys Ser Leu Arg Lys Ala165 170 175Leu Lys Glu His Gly Leu Leu Glu Asp Phe Leu Gln Lys Gln Gln Tyr180 185 190Gly Ile Ser Ser Lys Phe Met Asp Glu Pro Pro Gln Ser Pro Trp Asp195 200 205Arg Val Lys Asp Leu Ala Thr Val Tyr Val Asp Val Leu Lys Asp Ser210 215 220Gly Arg Asp Tyr Val Ser Gln Phe Glu Gly Ser Ala Leu Gly Lys Gln225 230 235 240Leu Asn Leu Lys Leu Leu Asp Asn Trp Asp Ser Val Thr Ser Thr Phe245 250 255Ser Lys Leu Arg Glu Gln Leu Gly Pro Val Thr Gln Glu Phe Trp Asp260 265 270Asn Leu Glu Lys Glu Thr Glu Gly Leu Arg Gln Glu Met Ser Lys Asp275 280 285Leu Glu Glu Val Lys Ala Lys Val Gln Pro Tyr Leu Asp Asp Phe Gln290 295 300Lys Lys Trp Gln Glu Glu Met Glu Leu Tyr Arg Gln Lys Val Glu Pro305 310 315 320Leu Arg Ala Glu Leu Gln Glu Gly Ala Arg Gln Lys Leu His Glu Leu325 330 335Gln Glu Lys Leu Ser Pro Leu Gly Glu Glu Met Arg Asp Arg Ala Arg340 345 350Ala His Val Asp Ala Leu Arg Thr His Leu Ala Pro Tyr Ser Asp Glu355 360 365Leu Arg Gln Arg Leu Ala Ala Arg Leu Glu Ala Leu Lys Glu Asn Gly370 375 380Gly Ala Arg Leu Ala Glu Tyr His Ala Lys Ala Thr Glu His Leu Ser
385 390 395 400Thr Leu Ser Glu Lys Ala Lys Pro Ala Leu Glu Asp Leu Arg Gln Gly405 410 415Leu Leu Pro Val Leu Glu Ser Phe Lys Val Ser Phe Leu Ser Ala Leu420 425 430Glu Glu Tyr Thr Lys Lys Leu Asn Thr Gln435 440<210>236<211>25<212>DNA<213>Artificial Sequence<220>
<223>forward primer 1226<400>236gcagcaccat ggctgatcac caccg 25<210>237<211>25<212>DNA<213>Artificial Sequence<220>
<223>forward primer 1227<400>237gtggtgaagc ttagacccct gcgcc 25<210>238<211>26<212>DNA<213>Artificial Sequence<220>
<223>forward primer 1228<400>238gcagcaaagc ttatggctga gatcac 26<210>239<211>24<212>DNA<213>Artificial Sequence<220>
<223>reverse primer 1229
<400>239gtgtgggatc ctcactgggt gttg24<210>240<211>248<212>PRT<213>Artificial Sequence<220>
<223>D9 scFV<400>240Asp Ile Val Met Thr Gln Ser Pro Ser Ser Leu Ala Met Ser Val Gly1 5 10 15Gln Arg Val Thr Met Arg Cys Lys Ser Ser Gln Ser Leu Leu Lys Ser20 25 30Thr Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln35 40 45Ser Pro Lys Leu Leu Val Tyr Phe Ala Ser Thr Arg Glu Ser Gly Val50 55 60Pro Asp Arg Phe Ile Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr65 70 75 80Ile Ser Ser Val Gln Ala Glu Asp Leu Ala Asp Tyr Phe Cys Gln Gln85 90 95His Tyr Asn Thr Pro Pro Thr Phe Gly Ala Gly Thr Lys Leu Glu Leu100 105 110Lys Arg Ser Pro Asn Gly Ala Ser His Ser Gly Ser Ala Pro Gly Thr115 120 125Ser Ser Ala Ser Gly Ser Gln Val His Leu Gln Gln Ser Gly Ala Glu130 135 140Leu Met Lys Pro Gly Ala Ser Met Lys Ile Ser Cys Lys Ala Thr Gly145 150 155 160Tyr Thr Phe Ser Ser Tyr Trp Ile Glu Trp Val Lys Gln Arg Pro Gly165 170 175His Gly Leu Glu Trp Ile Gly Glu Ile Leu Pro Gly Ser Gly Ser Thr
180 185 190Thr Tyr Asn Glu Lys Phe Lys Gly Lys Ala Thr Phe Thr Ala Asp Thr195 200 205Ser Ser Asn Thr Ala Tyr Met Gln Leu Ser Ser Leu Thr Ser Glu Asp210 215 220Ser Ala Val Tyr Tyr Cys Ala Arg Leu Asp Val Asp Ser Trp Gly Gln225 230 235 240Gly Thr Thr Leu Thr Val Ser Ser245<210>241<211>368<212>PRT<213>Mus musculus<400>241Met Ala Ala Val Ile Thr Trp Ala Leu Ala Leu Leu Ala Val Phe Ala1 5 10 15Ser Thr Gln Ala Arg Lys Ser Leu Trp Asp Tyr Phe Ser Gln Asn Ser20 25 30Trp Ser Lys Gly Val Met Gly Gln Pro Gln Lys Leu Ala Gln Glu Asn35 40 45Leu Lys Gly Ser Phe Glu Gln Asp Leu Tyr Asn Met Asn Asn Tyr Leu50 55 60Glu Lys Leu Gly Pro Leu Arg Gly Pro Gly Lys Glu Pro Pro Leu Leu65 70 75 80Ala Gln Asp Pro Glu Gly Ile Arg Lys Gln Leu Gln Gln Glu Leu Gly85 90 95Glu Val Ser Ser Arg Leu Glu Pro Tyr Met Ala Ala Lys His Gln Gln100 105 110Val Gly Trp Asn Leu Glu Gly Leu Arg Gln Gln Leu Lys Pro Tyr Thr115 120 125
Ala Glu Leu Met Glu Gln Val Gly Leu Ser Val Gln Glu Leu Gln Glu130 135 140Gln Leu Arg Val Val Gly Glu Asp Thr Lys Ala Gln Leu Leu Gly Gly145 150 155 160Val Asp Glu Ala Leu Asn Leu Leu Gln Asp Met Gln Ser Arg Val Leu165 170 175His His Thr Asp Arg Val Lys Glu Leu Phe His Pro Tyr Ala Glu Arg180 185 190Leu Val Thr Gly Ile Gly His His Val Gln Glu Leu His Arg Ser Val195 200 205Ala Pro His Ala Ala Ala Ser Pro Ala Arg Leu Ser Arg Cys Val Gln210 215 220Thr Leu Ser His Lys Leu Thr Arg Lys Ala Lys Asp Leu His Thr Ser225 230 235 240Ile Gln Arg Asn Leu Asp Gln Leu Arg Asp Glu Leu Ser Ala Phe Ile245 250 255Arg Val Ser Thr Asp Gly Ala Glu Asp Gly Asp Ser Leu Asp Pro Gln260 265 270Ala Leu Ser Glu Glu Val Arg Gln Arg Leu Gln Ala Phe Arg His Asp275 280 285Thr Tyr Leu Gln Ile Ala Ala Phe Thr Gln Ala Ile Asp Gln Glu Thr290 295 300Glu Glu Ile Gln His Gln Leu Ala Pro Pro Pro Pro Ser His Ser Ala305 310 315 320Phe Ala Pro Glu Leu Gly His Ser Asp Ser Asn Lys Ala Leu Ser Arg325 330 335Leu Gln Ser Arg Leu Asp Asp Leu Trp Glu Asp Ile Ala Tyr Gly Leu340 345 350Gln Asp Gln Gly His Ser His Leu Ser Asp Pro Glu Gly His Ser Gly355 360 365
<210>242<211>367<212>PRT<213>Rattus norvegicus<400>242Met Ala Ala Val Ile Thr Trp Ala Leu Ala Leu Leu Ser Val Phe Ala1 5 10 15Thr Val Gln Ala Arg Lys Ser Phe Trp Glu Tyr Phe Gly Gln Asn Ser20 25 30Gln Gly Lys Gly Met Met Gly Gln Gln Gln Lys Leu Ala Gln Glu Ser35 40 45Leu Lys Gly Ser Leu Glu Gln Asp Leu Tyr Asn Met Asn Asn Phe Leu50 55 60Glu Lys Leu Gly Pro Leu Arg Glu Pro Gly Lys Glu Pro Pro Arg Leu65 70 75 80Ala Gln Asp Pro Glu Gly Ile Arg Lys Gln Leu Gln Gln Glu Leu Glu85 90 95Glu Val Ser Thr Arg Leu Glu Pro Tyr Met Ala Ala Lys His Gln Gln100 105 110Val Gly Trp Asn Leu Glu Gly Leu Arg Gln Gln Leu Lys Pro Tyr Thr115 120 125Val Glu Leu Met Glu Gln Val Gly Leu Ser Val Gln Asp Leu Gln Glu130 135 140Gln Leu Arg Met Val Gly Lys Gly Thr Lys Ala Gln Leu Leu Gly Gly145 150 155 160Val Asp Glu Ala Met Ser Leu Leu Gln Asp Met Gln Ser Arg Val Leu165 170 175His His Thr Asp Arg Val Lys Glu Leu Phe His Pro Tyr Ala Glu Arg180 185 190Leu Val Thr Gly Ile Gly His His Val Gln Glu Leu His Arg Ser Val195 200 205
Ala Pro His Ala Val Ala Ser Pro Ala Arg Leu Ser Arg Cys Val Gln210 215 220Thr Leu Ser His Lys Leu Thr Arg Lys Ala Lys Asp Leu His Thr Ser225 230 235 240Ile Gln Arg Asn Leu Asp Gln Leu Arg Asp Glu Leu Ser Thr Phe Ile245 250 255Arg Val Ser Thr Asp Gly Ala Asp Asn Arg Asp Ser Leu Asp Pro Gln260 265 270Ala Leu Ser Asp Glu Val Arg Gln Arg Leu Gln Ala Phe Arg His Asp275 280 285Thr Tyr Leu Gln Ile Ala Ala Phe Thr Gln Ala Ile Asp Gln Glu Thr290 295 300Glu Glu Ile Gln His Gln Leu Ala Pro Pro Pro Pro Ser His Ser Ala305 310 315 320Phe Ala Pro Glu Leu Gly His Ser Asp Ser Asn Lys Ala Leu Ser Arg325 330 335Leu Gln Ser Arg Leu Asp Asp Leu Trp Glu Asp Ile Ala Tyr Gly Leu340 345 350His Asp Gln Gly His Ser Gln Asn Asn Pro Glu Gly His Ser Gly355 360 365<210>243<211>363<212>PRT<213>Homo sapiens<400>243Met Ala Ala Val Leu Thr Trp Ala Leu Ala Leu Leu Ser Ala Phe Ser1 5 10 15Ala Thr Gln Ala Arg Lys Gly Phe Trp Asp Tyr Phe Ser Gln Thr Ser20 25 30Gly Asp Lys Gly Arg Val Glu Gln Ile His Gln Gln Lys Met Ala Arg35 40 45
Glu Pro Ala Thr Leu Lys Asp Ser Leu Glu Gln Asp Leu Asn Asn Met50 55 60Asn Lys Phe Leu Glu Lys Leu Arg Pro Leu Ser Gly Ser Glu Ala Pro65 70 75 80Arg Leu Pro Gln Asp Pro Val Gly Met Arg Arg Gln Leu Gln Glu Glu85 90 95Leu Glu Glu Val Lys Ala Arg Leu Gln Pro Tyr Met Ala Glu Ala His100 105 110Glu Leu Val Gly Trp Asn Leu Glu Gly Leu Arg Gln Gln Leu Lys Pro115 120 125Tyr Thr Met Asp Leu Met Glu Gln Val Ala Leu Arg Val Gln Glu Leu130 135 140Gln Glu Gln Leu Arg Val Val Gly Glu Asp Thr Lys Ala Gln Leu Leu145 150 155 160Gly Gly Val Asp Glu Ala Trp Ala Leu Leu Gln Gly Leu Gln Ser Arg165 170 175Val Val His His Thr Gly Arg Phe Lys Glu Leu Phe His Pro Tyr Ala180 185 190Glu Ser Leu Val Ser Gly Ile Gly Arg His Val Gln Glu Leu His Arg195 200 205Ser Val Ala Pro His Ala Pro Ala Ser Pro Ala Arg Leu Ser Arg Cys210 215 220Val Gln Val Leu Ser Arg Lys Leu Thr Leu Lys Ala Lys Ala Leu His225 230 235 240Ala Arg Ile Gln Gln Asn Leu Asp Gln Leu Arg Glu Glu Leu Ser Arg245 250 255Ala Phe Ala Gly Thr Gly Thr Glu Glu Gly Ala Gly Pro Asp Pro Gln260 265 270Met Leu Ser Glu Glu Val Arg Gln Arg Leu Gln Ala Phe Arg Gln Asp275 280 285
Thr Tyr Leu Gln Ile Ala Ala Phe Thr Arg Ala Ile Asp Gln Glu Thr290 295 300Glu Glu Val Gln Gln Gln Leu Ala Pro Pro Pro Pro Gly His Ser Ala305 310 315 320Phe Ala Pro Glu Phe Gln Gln Thr Asp Ser Gly Lys Val Leu Ser Lys325 330 335Leu Gln Ala Arg Leu Asp Asp Leu Trp Glu Asp Ile Thr His Ser Leu340 345 350His Asp Gln Gly His Ser His Leu Gly Asp Pro355 360<210>244<211>368<212>PRT<213>Mus musculus<400>244Met Ala Ala Val Ile Thr Trp Ala Leu Ala Leu Leu Ala Val Phe Ala1 5 10 15Ser Thr Gln Ala Arg Lys Ser Leu Trp Asp Tyr Phe Ser Gln Asn Ser20 25 30Trp Ser Lys Gly Val Met Gly Gln Pro Gln Lys Leu Ala Gln Glu Asn35 40 45Leu Lys Gly Ser Phe Glu Gln Asp Leu Tyr Asn Met Asn Asn Tyr Leu50 55 60Glu Lys Leu Gly Pro Leu Arg Gly Pro Gly Lys Glu Pro Pro Leu Leu65 70 75 80Ala Gln Asp Pro Glu Gly Ile Arg Lys Gln Leu Gln Gln Glu Leu Gly85 90 95Glu Val Ser Ser Arg Leu Glu Pro Tyr Met Ala Ala Lys His Gln Gln100 105 110Val Gly Trp Asn Leu Glu Gly Leu Arg Gln Gln Leu Lys Pro Tyr Thr115 120 125
Ala Glu Leu Met Glu Gln Val Gly Leu Ser Val Gln Glu Leu Gln Glu130 135 140Gln Leu Arg Val Val Gly Glu Asp Thr Lys Ala Gln Leu Leu Gly Gly145 150 155 160Val Asp Glu Ala Leu Asn Leu Leu Gln Asp Met Gln Ser Arg Val Leu165 170 175His Gln Ala Asp Arg Val Lys Glu Leu Phe His Pro Tyr Ala Glu Arg180 185 190Leu Val Thr Gly Ile Gly His His Val Gln Glu Leu His Arg Ser Val195 200 205ALa Pro His Ala Ala Ala Ser Pro Ala Arg Leu Ser Arg Cys Val Gln210 215 220Thr Leu Ser His Lys Leu Thr Arg Lys Ala Lys Asp Leu His Thr Ser225 230 235 240Ile Gln Arg Asn Leu Asp Gln Leu Arg Asp Glu Leu Ser Ala Phe Ile245 250 255Arg Val Ser Thr Asp Gly Ala Glu Asp Gly Asp Ser Leu Asp Pro Gln260 265 270Ala Leu Ser Glu Glu Leu Arg Gln Arg Leu Gln Ala Phe Arg His Asp275 280 285Thr Tyr Leu Gln Ile Ala Ala Phe Thr Gln Ala Ile Asp Gln Glu Thr290 295 300Glu Glu Ile Gln His Gln Leu Ala Pro Pro Pro Pro Ser His Ser Ala305 310 315 320Phe Ala Pro Glu Leu Gly His Ser Asp Ser Asn Lys Ala Leu Ser Arg325 330 335Leu Gln Ser Arg Leu Asp Asp Leu Trp Glu Asp Ile Ala Tyr Gly Leu340 345 350Gln Asp Gln Gly His Ser His Leu Ser Asp Pro Glu Gly His Ser Gly
355 360 365<210>245<211>366<212>PRT<213>Homo sapiens<400>245Met Ala Ser Met Ala Ala Val Leu Thr Trp Ala Leu Ala Leu Leu Ser1 5 10 15Ala Phe Ser Ala Thr Gln Ala Arg Lys Gly Phe Trp Asp Tyr Phe Ser20 25 30Gln Thr Ser Gly Asp Lys Gly Arg Val Glu Gln Ile His Gln Gln Lys35 40 45Met Ala Arg Glu Pro Ala Thr Leu Lys Asp Ser Leu Glu Gln Asp Leu50 55 60Asn Asn Met Asn Lys Phe Leu Glu Lys Leu Arg Pro Leu Ser Gly Ser65 70 75 80Glu Ala Pro Arg Leu Pro Gln Asp Pro Val Gly Met Arg Arg Gln Leu85 90 95Gln Glu Glu Leu Glu Glu Val Lys Ala Arg Leu Gln Pro Tyr Met Ala100 105 110Glu Ala His Glu Leu Val Gly Trp Asn Leu Glu Gly Leu Arg Gln Gln115 120 125Leu Lys Pro Tyr Thr Met Asp Leu Met Glu Gln Val Ala Leu Arg Val130 135 140Gln Glu Leu Gln Glu Gln Leu Arg Val Val Gly Glu Asp Thr Lys Ala145 150 155 160Gln Leu Leu Gly Gly Val Asp Glu Ala Trp Ala Leu Leu Gln Gly Leu165 170 175Gln Ser Arg Val Val His His Thr Gly Arg Phe Lys Glu Leu Phe His180 185 190Pro Tyr Ala Glu Ser Leu Val Ser Gly Ile Gly Arg His Val Gln Glu
195 200 205Leu His Arg Ser Val Ala Pro His Ala Pro Ala Ser Pro Ala Arg Leu210 215 220Ser Arg Cys Val Gln Val Leu Ser Arg Lys Leu Thr Leu Lys Ala Lys225 230 235 240Ala Leu His Ala Arg Ile Gln Gln Asn Leu Asp Gln Leu Arg Glu Glu245 250 255Leu Ser Arg Ala Phe Ala Gly Thr Gly Thr Glu Glu Gly Ala Gly Pro260 265 270Asp Pro Gln Met Leu Ser Glu Glu Val Arg Gln Arg Leu Gln Ala Phe275 280 285Arg Gln Asp Thr Tyr Leu Gln Ile Ala Ala Phe Thr Arg Ala Ile Asp290 295 300Gln Glu Thr Glu Glu Val Gln Gln Gln Leu Ala Pro Pro Pro Pro Gly305 310 315 320His Ser Ala Phe Ala Pro Glu Phe Gln Gln Thr Asp Ser Gly Lys Val325 330 335Leu Ser Lys Leu Gln Ala Arg Leu Asp Asp Leu Trp Glu Asp Ile Thr340 345 350His Ser Leu His Asp Gln Gly His Ser His Leu Gly Asp Pro355 360 365<210>246<211>366<212>PRT<213>Homo sapiens<400>246Met Ala Ser Met Ala Ala Val Leu Thr Trp Ala Leu Ala Leu Leu Ser1 5 10 15Ala Phe Ser Ala Thr Gln Ala Arg Lys Gly Phe Trp Asp Tyr Phe Ser20 25 30Gln Thr Ser Gly Asp Lys Gly Arg Val Glu Gln Ile His Gln Gln Lys
35 40 45Met Ala Arg Glu Pro Ala Thr Leu Lys Asp Ser Leu Glu Gln Asp Leu50 55 60Asn Asn Met Asn Lys Phe Leu Glu Lys Leu Arg Pro Leu Ser Gly Ser65 70 75 80Glu Ala Pro Arg Leu Pro Gln Asp Pro Val Gly Met Arg Arg Gln Leu85 90 95Gln Glu Glu Leu Glu Glu Val Lys Ala Arg Leu Gln Pro Tyr Met Ala100 105 110Glu Ala His Glu Leu Val Gly Trp Asn Leu Glu Gly Leu Arg Gln Gln115 120 125Leu Lys Pro Tyr Thr Met Asp Leu Met Glu Gln Val Ala Leu Arg Val130 135 140Gln Glu Leu Gln Glu Gln Leu Arg Val Val Gly Glu Asp Thr Lys Ala145 150 155 160Gln Leu Leu Gly Gly Val Asp Glu Ala Trp Ala Leu Leu Gln Gly Leu165 170 175Gln Ser Arg Val Val His His Thr Gly Arg Phe Lys Glu Leu Phe His180 185 190Pro Tyr Ala Glu Ser Leu Val Ser Gly Ile Gly Arg His Val Gln Glu195 200 205Leu His Arg Ser Val Ala Pro His Ala Pro Ala Ser Pro Ala Arg Leu210 215 220Ser Arg Cys Val Gln Val Leu Ser Arg Lys Leu Thr Leu Lys Ala Lys225 230 235 240Ala Leu His Ala Arg Ile Gln Gln Asn Leu Asp Gln Leu Arg Glu Glu245 250 255Leu Ser Arg Ala Phe Ala Gly Thr Gly Thr Glu Glu Gly Ala Gly Pro260 265 270
Asp Pro Gln Met Leu Ser Glu Glu Val Arg Gln Arg Leu Gln Ala Phe275 280 285Arg Gln Asp Thr Tyr Leu Gln Ile Ala Ala Phe Thr Arg Ala Ile Asp290 295 300Gln Glu Thr Glu Glu Val Gln Gln Gln Leu Ala Pro Pro Pro Pro Gly305 310 315 320His Ser Ala Phe Ala Pro Glu Phe Gln Gln Thr Asp Ser Gly Lys Val325 330 335Leu Ser Lys Leu Gln Ala Arg Leu Asp Asp Leu Trp Glu Asp Ile Thr340 345 350His Ser Leu His Asp Gln Gly His Ser His Leu Gly Asp Pro355 360 365<210>247<211>368<212>PRT<213>Mus musculus<400>247Met Ala Ala Val Ile Thr Trp Ala Leu Ala Leu Leu Ala Val Phe Ala1 5 10 15Ser Thr Gln Ala Arg Lys Ser Leu Trp Asp Tyr Phe Ser Gln Asn Ser20 25 30Trp Ser Lys Gly Val Met Gly Gln Pro Gln Lys Leu Ala Gln Glu Asn35 40 45Leu Lys Gly Ser Phe Glu Gln Asp Leu Tyr Asn Met Asn Asn Tyr Leu50 55 60Glu Lys Leu Gly Pro Leu Arg Gly Pro Gly Lys Glu Pro Pro Leu Leu65 70 75 80Ala Gln Asp Pro Glu Asp Ile Arg Lys Gln Leu Gln Gln Glu Leu Gly85 90 95Glu Val Ser Ser Arg Leu Glu Pro Tyr Met Ala Ala Lys His Gln Gln100 105 110
Val Gly Trp Asn Leu Glu Gly Leu Arg Gln Gln Leu Lys Pro Tyr Thr115 120 125Ala Glu Leu Met Glu Gln Val Gly Leu Ser Val Gln Glu Leu Gln Glu130 135 140Gln Leu Arg Val Val Gly Glu Asp Thr Lys Ala Gln Leu Leu Gly Gly145 150 155 160Val Asp Glu Ala Leu Asn Leu Leu Gln Asp Met Gln Ser Arg Val Leu165 170 175His His Thr Asp Arg Val Lys Glu Leu Phe His Pro Tyr Ala Glu Arg180 185 190Leu Val Thr Gly Ile Gly His His Val Gln Glu Lau His Arg Ser Val195 200 205Ala Pro His Ala Ala Ala Ser Pro Ala Arg Leu Ser Arg Cys Val Gln210 215 220Thr Leu Ser His Lys Leu Thr Arg Lys Ala Lys Asp Leu His Thr Ser225 230 235 240Ile Gln Arg Asn Leu Asp Gln Leu Arg Asp Glu Lau Ser Ala Phe Ile245 250 255Arg Val Ser Thr Asp Gly Ala Glu Asp Gly Asp Ser Leu Asp Pro Gln260 265 270Ala Leu Ser Glu Glu Val Arg Gln Arg Leu Gln Ala Phe Arg His Asp275 280 285Thr Tyr Leu Gln Ile Ala Ala Phe Thr Gln Ala Ile Asp Gln Glu Thr290 295 300Glu Glu Ile Gln His Gln Lau Ala Pro Pro Pro Pro Ser His Ser Ala305 310 315 320Phe Ala Pro Glu Leu Gly His Ser Asp Ser Asn Lys Ala Leu Ser Arg325 330 335Leu Gln Ser Arg Leu Asp Asp Leu Trp Glu Asp Ile Ala Tyr Gly Leu340 345 350
Gln Asp Gln Gly His Ser His Leu Ser Asp Pro Glu Gly His Ser Gly355 360 365<210>248<211>363<212>PRT<213>Homo sapiens<400>248Met Ala Ala Val Leu Thr Trp Ala Leu Ala Leu Leu Ser Ala Phe Ser1 5 10 15Ala Thr Gln Ala Arg Lys Gly Phe Trp Asp Tyr Phe Ser Gln Thr Ser20 25 30Gly Asp Lys Gly Arg Val Glu Gln Ile His Gln Gln Lys Met Ala Arg35 40 45Glu Pro Ala Thr Leu Lys Asp Ser Leu Glu Gln Asp Leu Asn Asn Met50 55 60Asn Lys Phe Leu Glu Lys Leu Arg Pro Leu Ser Gly Ser Glu Ala Pro65 70 75 80Arg Leu Pro Gln Asp Pro Val Gly Met Arg Arg Gln Leu Gln Glu Glu85 90 95Leu Glu Glu Val Lys Ala Arg Leu Gln Pro Tyr Met Ala Glu Ala His100 105 110Glu Leu Val Gly Trp Asn Leu Glu Gly Leu Arg Gln Gln Leu Lys Pro115 120 125Tyr Thr Met Asp Leu Met Glu Gln Val Ala Leu Arg Val Gln Glu Leu130 135 140Gln Glu Gln Leu Arg Val Val Gly Glu Asp Thr Lys Ala Gln Leu Leu145 150 155 160Gly Gly Val Asp Glu Ala Trp Ala Leu Leu Gln Gly Leu Gln Ser Arg165 170 175Val Val His His Thr Gly Arg Phe Lys Glu Leu Phe His Pro Tyr Ala180 185 190
Glu Ser Leu Val Ser Gly Ile Gly Arg His Val Gln Glu Leu His Arg195 200 205Ser Val Ala Pro His Ala Pro Ala Ser Pro Ala Arg Leu Ser Arg Cys210 215 220Val Gln Val Leu Ser Arg Lys Leu Thr Leu Lys Ala Lys Ala Leu His225 230 235 240Ala Arg Ile Gln Gln Asn Leu Asp Gln Leu Arg Glu Glu Leu Ser Arg245 250 255Ala Phe Ala Gly Thr Gly Thr Glu Glu Gly Ala Gly Pro Asp Pro Gln260 265 270Met Leu Ser Glu Glu Val Arg Gln Arg Leu Gln Ala Phe Arg Gln Asp275 280 285Thr Tyr Leu Gln Ile Ala Ala Phe Thr Arg Ala Ile Asp Gln Glu Thr290 295 300Glu Glu Val Gln Gln Gln Leu Ala Pro Pro Pro Pro Gly His Ser Ala305 310 315 320Phe Ala Pro Glu Phe Gln Gln Thr Asp Ser Gly Lys Val Leu Ser Lys325 330 335Leu Gln Ala Arg Leu Asp Asp Leu Trp Glu Asp Ile Thr His Ser Leu340 345 350His Asp Gln Gly His Ser His Leu Gly Asp Pro355 360<210>249<211>363<212>PRT<213>Homo sapiens<400>249Met Ala Ala Val Leu Thr Trp Ala Leu Ala Leu Leu Ser Ala Phe Ser1 5 10 15Ala Thr Gln Ala Arg Lys Gly Phe Trp Asp Tyr Phe Ser Gln Thr Ser20 25 30
Gly Asp Lys Gly Arg Val Glu Gln Ile His Gln Gln Lys Met Ala Arg35 40 45Glu Pro Ala Thr Leu Lys Asp Ser Leu Glu Gln Asp Leu Asn Asn Met50 55 60Asn Lys Phe Lau Glu Lys Leu Arg Pro Leu Ser Gly Ser Glu Ala Pro65 70 75 80Arg Leu Pro Gln Asp Pro Val Gly Met Arg Arg Gln Leu Gln Glu Glu85 90 95Leu Glu Glu Val Lys Ala Arg Leu Gln Pro Tyr Met Ala Glu Ala His100 105 110Glu Leu Val Gly Trp Asn Leu Glu Gly Leu Arg Gln Gln Leu Lys Pro115 120 125Tyr Thr Met Asp Leu Met Glu Gln Val Ala Leu Arg Val Gln Glu Leu130 135 140Gln Glu Gln Leu Arg Val Val Gly Glu Asp Thr Lys Ala Gln Leu Leu145 150 155 160Gly Gly Val Asp Glu Ala Trp Ala Leu Leu Gln Gly Leu Gln Ser Arg165 170 175Val Val His His Thr Gly Arg Phe Lys Glu Leu Phe His Pro Tyr Ala180 185 190Glu Ser Leu Val Ser Gly Ile Gly Arg His Val Gln Glu Leu His Arg195 200 205Ser Val Ala Pro His Ala Pro Ala Ser Pro Ala Arg Leu Ser Arg Cys210 215 220Val Gln Val Leu Ser Arg Lys Leu Thr Leu Lys Ala Lys Ala Leu His225 230 235 240Ala Arg Ile Gln Gln Asn Leu Asp Gln Leu Arg Glu Glu Leu Ser Arg245 250 255Ala Phe Ala Gly Thr Gly Thr Glu Glu Gly Ala Gly Pro Asp Pro Gln260 265 270
Met Leu Ser Glu Glu Val Arg Gln Arg Leu Gln Ala Phe Arg Gln Asp275 280 285Thr Tyr Leu Gln Ile Ala Ala Phe Thr Arg Ala Ile Asp Gln Glu Thr290 295 300Glu Glu Val Gln Gln Gln Leu Ala Pro Pro Pro Pro Gly His Ser Ala305 310 315 320Phe Ala Pro Glu Phe Gln Gln Thr Asp Ser Gly Lys Val Leu Ser Lys325 330 335Leu Gln Ala Arg Leu Asp Asp Leu Trp Glu Asp Ile Thr His Ser Leu340 345 350His Asp Gln Gly His Ser His Leu Gly Asp Pro355 360<210>250<211>367<212>PRT<213>Rattus norvegicus<400>250Met Ala Ala Val Ile Thr Trp Ala Leu Ala Leu Leu Ser Val Phe Ala1 5 10 15Thr Val Gln Ala Arg Lys Ser Phe Trp Glu Tyr Phe Gly Gln Asn Ser20 25 30Gln Gly Lys Gly Met Met Gly Gln Gln Gln Lys Leu Ala Gln Glu Ser35 40 45Leu Lys Gly Ser Leu Glu Gln Asp Leu Tyr Asn Met Asn Asn Phe Leu50 55 60Glu Lys Leu Gly Pro Leu Arg Glu Pro Gly Lys Glu Pro Pro Arg Leu65 70 75 80Ala Gln Asp Pro Glu Gly Ile Arg Lys Gln Leu Gln Gln Glu Leu Glu85 90 95Glu Val Ser Thr Arg Leu Glu Pro Tyr Met Ala Ala Lys His Gln Gln100 105 110
Val Gly Trp Asn Leu Glu Gly Leu Arg Gln Gln Leu Lys Pro Tyr Thr115 120 125Val Glu Leu Met Glu Gln Val Gly Leu Ser Val Gln Asp Leu Gln Glu130 135 140Gln Leu Arg Met Val Gly Lys Gly Thr Lys Ala Gln Leu Leu Gly Gly145 150 155 160Val Asp Glu Ala Met Ser Leu Leu Gln Asp Met Gln Ser Arg Val Leu165 170 175His His Thr Asp Arg Val Lys Glu Leu Phe His Pro Tyr Ala Glu Arg180 185 190Leu Val Thr Gly Ile Gly His His Val Gln Glu Leu His Arg Ser Val195 200 205Ala Pro His Ala Val Ala Ser Pro Ala Arg Leu Ser Arg Cys Val Gln210 215 220Thr Leu Ser His Lys Leu Thr Arg Lys Ala Lys Asp Leu His Thr Ser225 230 235 240Ile Gln Arg Asn Leu Asp Gln Leu Arg Asp Glu Leu Ser Thr Phe Ile245 250 255Arg Val Ser Thr Asp Gly Ala Asp Asn Arg Asp Ser Leu Asp Pro Gln260 265 270Ala Leu Ser Asp Glu Val Arg Gln Arg Leu Gln Ala Phe Arg His Asp275 280 285Thr Tyr Leu Gln Ile Ala Ala Phe Thr Gln Ala Ile Asp Gln Glu Thr290 295 300Glu Glu Ile Gln His Gln Leu Ala Pro Pro Pro Pro Ser His Ser Ala305 310 315 320Phe Ala Pro Glu Leu Gly His Ser Asp Ser Asn Lys Ala Leu Ser Arg325 330 335Leu Gln Ser Arg Leu Asp Asp Leu Trp Glu Asp Ile Ala Tyr Gly Leu
340 345 350His Asp Gln Gly His Ser Gln Asn Asn Pro Glu Gly His Ser Gly355 360 365<210>251<211>367<212>PRT<213>Rattus norvegicus<400>251Met Ala Ala Val Ile Thr Trp Ala Leu Ala Leu Leu Ser Val Phe Ala1 5 10 15Thr Val Gln Ala Arg Lys Ser Phe Trp Glu Tyr Phe Gly Gln Asn Ser20 25 30Gln Gly Lys Gly Met Met Gly Gln Gln Gln Lys Leu Ala Gln Glu Ser35 40 45Leu Lys Gly Ser Leu Glu Gln Asp Leu Tyr Asn Met Asn Asn Phe Leu50 55 60Glu Lys Leu Gly Pro Leu Arg Glu Pro Gly Lys Glu Pro Pro Arg Leu65 70 75 80Ala Gln Asp Pro Glu Gly Ile Arg Lys Gln Leu Gln Gln Glu Leu Glu85 90 95Glu Val Ser Thr Arg Leu Glu Pro Tyr Met Ala Ala Lys His Gln Gln100 105 110Val Gly Trp Asn Leu Glu Gly Leu Arg Gln Gln Leu Lys Pro Tyr Thr115 120 125Val Glu Leu Met Glu Gln Val Gly Leu Ser Val Gln Asp Leu Gln Glu130 135 140Gln Leu Arg Met Val Gly Lys Gly Thr Lys Ala Gln Leu Leu Gly Gly145 150 155 160Val Asp Glu Ala Met Ser Leu Leu Gln Asp Met Gln Ser Arg Val Leu165 170 175His His Thr Asp Arg Val Lys Glu Leu Phe His Pro Tyr Ala Glu Arg
180 185 190Leu Val Thr Gly Ile Gly His His Val Gln Glu Leu His Arg Ser Val195 200 205Ala Pro His Ala Val Ala Ser Pro Ala Arg Lau Ser Arg Cys Val Gln210 215 220Thr Leu Ser His Lys Leu Thr Arg Lys Ala Lys Asp Leu His Thr Ser225 230 235 240Ile Gln Arg Asn Leu Asp Gln Leu Arg Asp Glu Leu Ser Thr Phe Ile245 250 255Arg Val Ser Thr Asp Gly Ala Asp Asn Arg Asp Ser Leu Asp Pro Gln260 265 270Ala Leu Ser Asp Glu Val Arg Gln Arg Leu Gln Ala Phe Arg His Asp275 280 285Thr Tyr Leu Gln Ile Ala Ala Phe Thr Gln Ala Ile Asp Gln Glu Thr290 295 300Glu Glu Ile Gln His Gln Leu Ala Pro Pro Pro Pro Ser His Ser Ala305 310 315 320Phe Ala Pro Glu Leu Gly His Ser Asp Ser Asn Lys Ala Leu Ser Arg325 330 335Leu Gln Ser Arg Leu Asp Asp Leu Trp Glu Asp Ile Ala Tyr Gly Leu340 345 350His Asp Gln Gly His Ser Gln Asn Asn Pro Glu Gly His Ser Gly355 360 36权利要求
1.一种在植物中表达载脂蛋白的方法，包括(a)提供嵌合核酸构建体，所述构建体包括在5’至3’转录方向可操作连接的下列成份(i)能够在植物细胞中控制表达的核酸序列；和(ii)编码载脂蛋白多肽的核酸序列；(b)把嵌合核酸构建体导入植物细胞内；以及(c)让植物细胞成长为成熟植物，其中植物表达载脂蛋白。
2.权利要求1的方法，其中将嵌合核酸序列在核基因组整合条件下导入植物细胞内。
3.权利要求1或2的方法，其中该植物细胞是种子细胞。
4.权利要求1、2或3的方法，其中能够在植物细胞中控制表达的核酸序列是种子优选启动子。
5.权利要求4的方法，其中种子优选启动子是菜豆蛋白启动子。
6.权利要求1或2的方法，其中能够在植物细胞中控制表达的核酸序列是组成型启动子。
7.权利要求6的方法，其中该组成型启动子是遍在蛋白启动子。
8.权利要求1的方法，其中嵌合核酸构建体还包括编码稳定多肽的核酸序列，该核酸序列符合读框地连接于编码载脂蛋白的核酸序列。
9.权利要求8的方法，其中稳定多肽是植物特异性的。
10.权利要求8的方法，其中稳定多肽是非植物特异性的。
11.权利要求9的方法，其中该植物特异性稳定多肽是油体蛋白或硫氧还蛋白或它们的片段。
12.权利要求11的方法，其中该油体蛋白选自油质蛋白、caleosin和steroleosin。
13.权利要求12的方法，其中所述油质蛋白、caleosin和steroleosin来自拟南芥(Arabidopsis thalania)。
14.权利要求11的方法，其中该硫氧还蛋白为SEQ ID NO56。
15.权利要求10的方法，其中该非植物特异性稳定多肽是绿色荧光蛋白或单链抗体或它们的片段。
16.权利要求10的方法，其中该非植物特异性稳定多肽经过密码子优化以便在植物内最适表达。
17.权利要求15的方法，其中该绿色荧光蛋白是SEQ ID NO57。
18.权利要求15的方法，其中单链抗体能够促进对种子内表达的载脂蛋白的纯化。
19.权利要求15的方法，其中该单链抗体能够与油体蛋白特异性结合。
20.权利要求15的方法，其中该单链抗体是能够与来自拟南芥的18kDa油质蛋白特异性结合的单链Fv抗体(D9scFv)。
21.权利要求15的方法，其中该单链抗体是SEQ ID NO240。
22.权利要求8的方法，其中该稳定多肽通过可裂解接头连接于载脂蛋白。
23.权利要求22的方法，其中该可裂解接头是凝乳酶序列原。
24.权利要求23的方法，其中该凝乳酶序列原是SEQ ID NO143。
25.权利要求1的方法，其中嵌合核酸序列还包括导向信号，其能够把载脂蛋白导向ER或ER衍生贮存小泡。
26.权利要求25的方法，其中所述衍生贮存小泡是油体，且所述导向序列编码油体蛋白。
27.权利要求25的方法，其中所述导向信号包括羧基末端ER保留基序。
28.权利要求27的方法，其中所述羧基末端ER保留基序是KDEL。
29.权利要求1的方法，其中所述嵌合核酸构建体还包括编码信号肽的核酸序列，所述信号肽能够将载脂蛋白多肽导向质外体。
30.权利要求29的方法，其中所述信号肽是烟草致病相关蛋白(PR-S)信号序列。
31.权利要求30的方法，其中所述PR-S信号序列是SEQ ID NO58。
32.权利要求1至31中任一项的方法，其中编码载脂蛋白的核酸序列选自人载脂蛋白、人载脂蛋白原、猪载脂蛋白、猪载脂蛋白原、牛载脂蛋白、和牛载脂蛋白原的核酸序列。
33.权利要求1至32中任一项的方法，其中编码载脂蛋白的核酸序列经植物密码子使用优化。
34.一种获得包括载脂蛋白的植物种子的方法，包括(a)提供嵌合核酸构建体，所述构建体包括在5’至3’转录方向可操作连接的下列成份(i)能够在植物种子细胞内控制表达之核酸序列；和(ii)编码载脂蛋白多肽的核酸序列；(b)将嵌合核酸构建体导入植物细胞内；(c)使物细胞成长为成熟植物，并从该植物获得组织，其中种子包括载脂蛋白；以及(d)从该植物获得种子，其中种子包括载脂蛋白。
35.一种植物，其包括嵌合核酸序列，所述序列在5’至3’转录方向包括(a)能够在植物内控制表达的第一核酸序列，其可操作地连接于；(b)编码载脂蛋白多肽的第二核酸序列，其中植物含有载脂蛋白。
36.权利要求35的植物，其中嵌合核酸序列整合于植物核基因组内。
37.权利要求1至36中任一项的植物，其中所用植物为拟南芥或红花植物。
38.一种植物种子，其包括嵌合核酸序列，所述序列在5’至3’转录方向包括(a)能够在植物种子内控制表达的第一核酸序列，其可操作地连接于；(b)编码载脂蛋白多肽的第二核酸序列。
39.一种组合物，其包括基本上纯的油体，所述油体包括从植物获得的载脂蛋白。
40.一种编码载脂蛋白的核酸序列，其连接于包括能够在植物细胞内控制表达的核酸的核酸序列。
41.权利要求40的核酸序列，其中该植物细胞是种子细胞。
42.权利要求41的核酸序列，其中所述能够在植物细胞内控制表达的核酸序列是种子优选启动子。
43.权利要求43的核酸，其中所述种子优选启动子是菜豆蛋白启动子。
44.权利要求43的核酸序列，其中所述能够在植物种子内控制表达的核酸序列是组成型启动子。
45.权利要求44的核酸序列，其中所述启动子是遍在蛋白启动子。
46.一种适于在植物细胞内表达的重组表达载体，其包括权利要求1至45中任一项的核酸序列。
47.一种基本上纯的载脂蛋白的制备方法，包括(a)提供嵌合核酸构建体，所述构建体包括在5’至3’转录方向可操作连接的下列成份(i)能够在植物种子细胞内控制表达的核酸序列；和(ii)编码载脂蛋白多肽的核酸序列；(b)将嵌合核酸构建体导入植物细胞内；(c)让植物细胞成长为成熟植物；(d)从该植物获得种子，其中种子包括载脂蛋白；和(e)从植物种子成份中分离载脂蛋白，以获得基本上纯的载脂蛋白。
48.根据权利要求1至38中任一项所制备的植物用于获得基本上纯的载脂蛋白的用途。
49.一种组合物，其包括自植物获得的基本上纯的载脂蛋白。
全文摘要
本发明公开了在植物中生产载脂蛋白的方法。本发明在一实施方式中提供了在植物中表达载脂蛋白的方法，包括(a)提供嵌合核酸构建体，其包括在转录的5’至3’方向可操作连接的下列成份(i)能够控制在植物细胞内表达之核酸序列；和(ii)编码载脂蛋白多肽之核酸序列；(b)把嵌合核酸构建体导入植物细胞内；以及让植物细胞长成成熟植物，能够结籽，其中的种子表达载脂蛋白。
文档编号C07K14/775GK1906296SQ200480040450
公开日2007年1月31日 申请日期2004年11月15日 优先权日2003年11月14日
发明者莫里斯·M.·莫洛尼, 亚历山德拉·里德 申请人:赛姆生物系统遗传公司