CN112204136B - 植酸酶突变体 - Google Patents
植酸酶突变体 Download PDFInfo
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- CN112204136B CN112204136B CN201980036097.2A CN201980036097A CN112204136B CN 112204136 B CN112204136 B CN 112204136B CN 201980036097 A CN201980036097 A CN 201980036097A CN 112204136 B CN112204136 B CN 112204136B
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Abstract
本发明涉及热稳定性植酸酶，在野生型大肠杆菌植酸酶或突变型大肠杆菌植酸酶的氨基酸序列中包含至少一对引入的二硫键，引入后可以提升植酸酶的性质，特别是在于耐热稳定性，耐蒸汽稳定性，制粒稳定性方面，显著优于现有的野生型或者突变型植酸酶；相比于现有的引入二硫键的工程改造植酸酶，其耐热稳定性也有显著提高。
Description
技术领域
本发明属于蛋白质工程领域，涉及来源于革兰氏阴性菌的植酸酶，尤其是大肠杆菌植酸酶，此类经引入一对或多对二硫键而改造后，热稳定性得到提升。
背景技术
植酸酶(Phytase),即肌醇六磷酸磷酸水解酶(myo-Inositol hexakisphosphatephosphohydrolase)，属于正磷酸单酯磷酸水解酶,催化植酸水解生成低级肌醇磷酸衍生物和无机磷酸，在某些情况下可将植酸水解为游离的肌醇。植酸在谷物、豆类、油料等作物种子中含量最为丰富，高达1％～3％，占植物总磷含量的60％～80％。但植酸中的磷不能被直接吸收利用，必须在消化道内先水解为无机磷酸盐。研究表明，单胃动物(猪、鸡、鸭、鹅等)因为缺乏植酸酶而对植酸中磷的利用率很低。同时，植酸强烈电负性导致其通常与二价或三价阳离子，如Ca2+、Zn2+、Fe2++等形成不溶性盐类，阻碍小肠对矿物质的吸收。还会与蛋白质，氨基酸以及脂肪酸等形成络合物，影响他们的吸收利用，植酸还会与胃蛋白酶、胰凝乳酶、胰蛋白酶等结合，降低消化酶活性。因此，在单胃动物饲料中添加植酸酶可提高动物饲料中磷的利用率，降低动物排泄物中的磷含量，同时能提高蛋白和饲料能量利用率。
植酸酶作为饲料添加剂预先加入饲料原料中，经高温制粒等过程(70-95度，时间为30秒-120秒)后，生产出饲料用于动物饲养。因此为了最大化发挥植酸酶作用，需要其耐受较高的温度，或者说植酸酶应有良好的耐热性。商业化的植酸酶主要来源于黑曲霉(如US5436156所述)，大肠杆菌(如US7432098所述)，柠檬酸细菌属(如US20100261259所述Citrobacter braakii菌)，布氏杆菌(如US8143046所述的Buttiauxella sp.菌)等。这些植酸酶由于来源不同，导致他们具有不同的耐酸耐热性质。Nielsen等(J Agric FoodChem.2015,63(3):943-50)比较了商业化的植酸酶性质，结果显示大肠杆菌植酸酶显示出最好的特性。文中描述的大肠杆菌植酸酶产品是经过蛋白质工程修饰的突变体，因此具有更好热稳定性。US8540984，US9765313，US7432098和US8877478描述了通过对大肠杆菌植酸酶序列进行随机突变和定点突变筛选后获得的热稳定性提高的突变体酶，而US20130017185以及US20170240872专利申请中提到了根据大肠杆菌植酸酶蛋白质三维结构进行特定二硫键引入也可以提高酶热稳定性。
本领域还需要提供更多的具有热稳定性的植酸酶。
发明内容
本发明人发现，通过在大肠杆菌野生型植酸酶(例如与SEQ ID NO:1所示的大肠杆菌野生型植酸酶具有大于85％的序列一致性者)或者大肠杆菌植酸酶突变体(例如与SEQID NO:2所示的大肠杆菌植酸酶突变体具有大于75％的序列一致性者)的氨基酸序列中的特定位置上引入一对或多对二硫键，可以提高其稳定性，从而实现了发明的目的。
在一些实施方案中，在与SEQ ID NO:1所示的大肠杆菌野生型植酸酶具有大于85％的序列一致性的大肠杆菌植酸酶突变体的氨基酸序列中特定位置上引入如表1所示的一对或多对二硫键。在一些优选实施方案中，在与SEQ ID NO:1所示的大肠杆菌野生型植酸酶具有大于88％、89％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％的序列一致性的大肠杆菌植酸酶的氨基酸序列中特定位置上引入如表1所示的一对或多对二硫键。
在另一些实施方案中，在与SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:79或SEQ IDNO:99所示的大肠杆菌植酸酶突变体具有大于75％的序列一致性的大肠杆菌植酸酶变体的氨基酸序列中特定位置上引入如表1所示的一对或多对二硫键。在一些优选实施方案中，在与SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:79或SEQ ID NO:99所示的大肠杆菌植酸酶突变体具有大于80％、82％、84％、86％、88％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％的序列一致性的大肠杆菌植酸酶变体的氨基酸序列中特定位置上引入如表1所示的一对或多对二硫键。
在一些实施方案中，所述突变型大肠杆菌植酸酶与如SEQ ID NO:1所示的野生型大肠杆菌植酸酶相比，在至少1个位置上具有突变：1,25,30,36,37,38,39,46,55,60,62,65,69,70,73,74,75,76,77,79,80,85,101,108,109,111,114,116,118,120,123,126,127,133,137,138,139,141,142,146,151,157,159,161,173,176,178,180,183,184,185,186,187,188,189,204,211,233,235,245,253,255,267,276,282,283,284,286,287,288,291,295,297,311,315,317,318,327,341,354,363,367,369,370,380,382,383,385,391,402,408。在一些优选实施方案中，所述突变型大肠杆菌植酸酶与如SEQ ID NO:1所示的野生型大肠杆菌植酸酶相比，在至少1个位置上具有突变：25，46，62，70，73，74，75，76，114，137，142，146，159，173，204，255，282，283，284。在一些更优选的实施方案中，所述突变型大肠杆菌植酸酶与如SEQ ID NO:1所示的野生型大肠杆菌植酸酶相比，在至少1个位置上具有突变：25，46，62，70，73，74，75，76，114，137，142，146，159，173，204，255。
在一些具体实施方案中，所述突变型大肠杆菌植酸酶与如SEQ ID NO:1所示的野生型大肠杆菌植酸酶相比，在如下位置上包含突变：46，62，73，75，146，159，204，255。在另一些具体实施方案中，所述突变型大肠杆菌植酸酶与如SEQ ID NO:1所示的野生型大肠杆菌植酸酶相比，在如下位置上包含突变：25，46，62，70，73，75，114，137，142，146，159，255。在一些具体实施方案中，所述突变型大肠杆菌植酸酶与如SEQ ID NO:1所示的野生型大肠杆菌植酸酶相比，在如下位置上包含突变：46，62，70，73，74，75，76，146，159，173，255，282，283，284。在另一些具体实施方案中，所述突变型大肠杆菌植酸酶与如SEQ ID NO:1所示的野生型大肠杆菌植酸酶相比，在如下位置上包含突变：25，46，62，70，73，74，75，114，137，142，146，159，173，255，282，283，284。
在一些实施方案中，所述突变型大肠杆菌植酸酶与如SEQ ID NO:1所示的野生型大肠杆菌植酸酶相比，具有至少一个如下突变：Q1S,Q1V,Q1N,A25F,Q30K,A36K,W37F,P38Y,T39D,W46E,I55V,H60S,H60Q,Q62W,R65H,D69N,G70E,A73P,A73D,A73E,K74D,K74P,K74L,K74N,K75C,K75Q,G76T,C77A,Q79L,Q79R,Q79A,Q79G,Q79F,S80P,I85V,A101L,C108A,A109D,A109E,A109G,A109F,A109P,T111S,T111D,T111Q,T114H,T116A,T118R,T118S,S120R,P123E,N126Y,P127V,P127L,C133A,N137V,N137E,N137S,N137P,A138V,A138H,A138D,A138P,N139P,N139A,N139H,T141R,T141E,T141G,T141A,D142R,S146E,S146R,S151P,G157R,G157Q,G157N,G157L,G157A,R159Y,T161P,P173Y,P173S,N176P,N176K,C178A,K183R,Q184S,D185N,D185L,E186V,E186A,S187P,C188A,S189T,N204C,V211W,G233E,G235Y,T245E,Q253V,Y255D,R267A,H282N,P283G,P284T,K286F,Q287Y,A288E,A288R,A288V,V291I,T295I,V297T,G311S,E315G,E315S,N317L,W318Y,T327Y,L341Y,L341V,F354Y,K363A,K363L,S367F,N369P,T370P,A380P,A380R,A380T,C382A,E383S,R385S,R385V,R385T,C391A,E402R,E402T,E402D,E402P,E402N,C408A。在一些优选实施方案中，所述突变型大肠杆菌植酸酶与如SEQ ID NO:1所示的野生型大肠杆菌植酸酶相比，具有至少一个如下突变：A25F，W46E，Q62W，G70E，A73P，K74N，K75C，K75Q，G76T，T114H，N137V，D142R，S146E，R159Y，P173S，N204C，Y255D，H282N，P283G，P284T。在一些更优选的实施方案中，所述突变型大肠杆菌植酸酶与如SEQ ID NO:1所示的野生型大肠杆菌植酸酶相比，具有至少一个如下突变：A25F，W46E，Q62W，G70E，A73P，K74N，K75C，K75Q，G76T，T114H，N137V，D142R，S146E，R159Y，P173S，N204C，Y255D。
在一些实施方案中，所述突变型大肠杆菌植酸酶与如SEQ ID NO:1所示的野生型大肠杆菌植酸酶相比，具有至少一个如下突变：W46E，Q62W，A73P，K75C，S146E，R159Y，N204C，Y255D。在另一些实施方案中，所述突变型大肠杆菌植酸酶与如SEQ ID NO:1所示的野生型大肠杆菌植酸酶相比，具有至少一个如下突变：A25F,W46E,Q62W,G70E,A73P,K75C,T114H,N137V,D142R,S146E,R159Y,Y255D。在一些实施方案中，所述突变型大肠杆菌植酸酶与如SEQ ID NO:1所示的野生型大肠杆菌植酸酶相比，具有至少一个如下突变：W46E,Q62W,G70E,A73P,K74N,K75Q,G76T,S146E,R159Y,P173S,Y255D,H282N,P283G,P284T。在另一些实施方案中，所述突变型大肠杆菌植酸酶与如SEQ ID NO:1所示的野生型大肠杆菌植酸酶相比，具有至少一个如下突变：A25F,W46E,Q62W,G70E,A73P,K74N,K75Q,T114H,N137V,D142R,S146E,R159Y,P173S,Y255D,H282N,P283G,P284T。
在一些具体实施方案中，所述突变型大肠杆菌植酸酶与如SEQ ID NO:1所示的野生型大肠杆菌植酸酶相比，包含如下突变：W46E，Q62W，A73P，K75C，S146E，R159Y，N204C，Y255D。在另一些具体实施方案中，所述突变型大肠杆菌植酸酶与如SEQ ID NO:1所示的野生型大肠杆菌植酸酶相比，包含如下突变：A25F,W46E,Q62W,G70E,A73P,K75C,T114H,N137V,D142R,S146E,R159Y,Y255D。在一些具体实施方案中，所述突变型大肠杆菌植酸酶与如SEQ ID NO:1所示的野生型大肠杆菌植酸酶相比，包含如下突变：W46E,Q62W,G70E,A73P,K74N,K75Q,G76T,S146E,R159Y,P173S,Y255D,H282N,P283G,P284T。在另一些具体实施方案中，所述突变型大肠杆菌植酸酶与如SEQ ID NO:1所示的野生型大肠杆菌植酸酶相比，包含如下突变：A25F,W46E,Q62W,G70E,A73P,K74N,K75Q,T114H,N137V,D142R,S146E,R159Y,P173S,Y255D,H282N,P283G,P284T。
具体而言，本发明人发现，在如SEQ ID NO:1所示的大肠杆菌野生型植酸酶序列或如SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:79或SEQ ID NO:99所示的大肠杆菌突变型植酸酶序列中分别引入如表1中所示的一对或多对二硫键组合，可以提高其热稳定性。
表1：引入二硫键名称和位置(氨基酸位置编号以SEQ ID NO:1为准)
在一些实施方案中，在野生型或突变型大肠杆菌植酸酶中引入的一对或多对二硫键，所述二硫键选自(A)、(B)、(C)、(D)、(E)、(J)、(M)或(O)中的至少一项，条件式(C)和(D)项不同时满足。
在一些实施方案中，在野生型或突变型大肠杆菌植酸酶中引入的一对二硫键，所述二硫键选自(A)、(B)、(C)、(D)、(E)、(J)、(M)或(O)项。
在一些实施方案中，在野生型或突变型大肠杆菌植酸酶中同时引入多对二硫键，优选地，在野生型或突变型植酸酶中同时引入(B)+(O)、(C)+(O)、(M)+(O)、(B)+(D)+(O)或(D)+(M)+(O)所述的二硫键；更优选地，在野生型或突变型大肠杆菌植酸酶中同时引入(B)+(O)或(C)+(O)所述的二硫键。
为本发明的目的，“引入”不限定二硫键是以任何特定的方式生成的。例如，“引入”二硫键，可以包括将待引入二硫键的植酸酶序列的相应位置上的氨基酸残基替换成能够形成二硫键的氨基酸残基(包括，例如，半胱氨酸残基Cys，同型半胱氨酸残基Hcy，等等)；和/或在相应位置上插入能够形成二硫键的氨基酸残基。这样的替换和/或插入可以，例如，通过本领域公知的定点诱变方法来实现。“引入”亦包括形成所述二硫键的任何一个或两个氨基酸残基是由于自然突变而产生的情况。
为了生产经过如此改造的突变体，可以使用微生物细菌如大肠杆菌，真菌如酵母(毕赤酵母，粟酒裂殖酵母等)和丝状真菌(如黑曲霉，米曲霉，里氏木霉等)，以及植物(如玉米，大豆，小麦等)作为宿主进行表达。
表达和生产上述突变体使用通用的和已知技术即可完成。如APPLIED ANDENVIRONMENTAL MICROBIOLOGY,2004,3041–3046描述了大肠杆菌植酸酶及突变体在大肠杆菌中的表达，Journal of Biotechnology 175(2014)1–6描述了植酸酶及突变体在毕赤酵母中的表达，专利申请CN107353327描述了植酸酶及突变体在黑曲霉中表达。
为了构建上述突变，可以在已有野生型核酸序列基础上使用常规的定点突变方法，也可以使用基因合成方法从头合成。在连接启动子和终止子后导入到宿主细胞中，在合适的培养条件下进行表达。上述方法为本领域常规方法。
“野生型植酸酶”中是指植酸酶由天然存在的微生物，如在自然界中发现的大肠杆菌细胞中表达的植酸酶。
“变体”或“突变型”是指具有植酸酶活性的包含在一个或多个(数个)位置的一个或多个(数个)氨基酸残基的变更，即取代、插入和/或缺失的多肽。取代是指用不同的氨基酸替代占据某位置的氨基酸；缺失是指除去占据某位置的氨基酸；而插入是指在占据某位置的氨基酸邻接处且在之后添加1-5个氨基酸。对野生型植酸酶进行突变，也是指与野生型植酸酶相比，在至少一个位置上进行氨基酸的取代、插入和/或缺失，优选地，是指在至少一个位置上进行氨基酸的取代，如“A25F”，即为野生型植酸酶第25位丙氨酸取代位苯丙氨酸。
“(B)+(O)”、“B+O”或“(B)项+(O)项”指在野生型或突变型植酸酶序列的中引入两个二硫键，既在(B)项所述的两个位置上形成二硫键，又在(O)项所述的两个位置上形成二硫键；同理发明中所述(C)项+(O)项，(M)项+(O)项，(B)项+(D)项+(O)项和(D)项+(M)项+(O)项等带“+”的描述具有类似的解释。
“序列一致性”定义为对比序列并在必要时引入缺口以获取最大百分比序列同一性后，且不将任何保守替代视为序列同一性的一部分，候选序列中与特定肽或多肽序列中的氨基酸残基相同的氨基酸残基的百分率。可以本领域技术范围内的多种方式进行序列对比以测定百分比氨基酸序列同一性，例如使用公众可得到的计算机软件，诸如BLAST、BLAST-2、ALIGN或Megalign(DNASTAR)软件。本领域技术人员可决定测量对比的适宜参数，包括对所比较的序列全长获得最大对比所需的任何算法。
基于该发现，本申请提供下述技术方案。
1.一种热稳定性植酸酶，其特征在于，在野生型大肠杆菌植酸酶或突变型大肠杆菌植酸酶的氨基酸序列中包含至少一对引入的二硫键，所述野生型大肠杆菌植酸酶的氨基酸序列如SEQ ID NO:1所示，所述突变型大肠杆菌植酸酶与如SEQ ID NO:1所示的野生型大肠杆菌植酸酶相比，在至少1个位置上具有突变，
并且，所述引入的二硫键选自：
(A)与SEQ ID NO:1的第34位对应的位置上的氨基酸残基、以及与SEQ ID NO:1的第174位对应的位置上的氨基酸残基之间形成的二硫键；
(B)与SEQ ID NO:1的第56位对应的位置上的氨基酸残基、且与SEQ ID NO:1的第103位对应的位置上的氨基酸残基之间形成的二硫键；
(C)与SEQ ID NO:1的第57位对应的位置上的氨基酸残基、以及与SEQ ID NO:1的第366位对应的位置上的氨基酸残基之间形成的二硫键；
(D)与SEQ ID NO:1的第61位对应的位置上的氨基酸残基、以及与SEQ ID NO:1的第366位对应的位置上的氨基酸残基之间形成的二硫键；
(E)与SEQ ID NO:1的第82位对应的位置上的氨基酸残基、以及与SEQ ID NO:1的第296位对应的位置上的氨基酸残基之间形成的二硫键；
(F)与SEQ ID NO:1的第128位对应的位置上的氨基酸残基、以及与SEQ ID NO:1的第203位对应的位置上的氨基酸残基之间形成的二硫键；
(G)与SEQ ID NO:1的第140位对应的位置上的氨基酸残基、以及与SEQ ID NO:1的第262位对应的位置上的氨基酸残基之间形成的二硫键；
(H)与SEQ ID NO:1的第156位对应的位置上的氨基酸残基、以及与SEQ ID NO:1的第191位对应的位置上的氨基酸残基之间形成的二硫键；
(I)与SEQ ID NO:1的第165位对应的位置上的氨基酸残基、以及与SEQ ID NO:1的第245位对应的位置上的氨基酸残基之间形成的二硫键；
(J)与SEQ ID NO:1的第191位对应的位置上的氨基酸残基、以及与SEQ ID NO:1的第210位对应的位置上的氨基酸残基之间形成的二硫键；
(K)与SEQ ID NO:1的第196位对应的位置上的氨基酸残基、以及与SEQ ID NO:1的第211位对应的位置上的氨基酸残基之间形成的二硫键；
(L)与SEQ ID NO:1的第264位对应的位置上的氨基酸残基、以及与SEQ ID NO:1的第312位对应的位置上的氨基酸残基之间形成的二硫键；
(M)与SEQ ID NO:1的第315位对应的位置上的氨基酸残基、以及与SEQ ID NO:1的第380位对应的位置上的氨基酸残基之间形成的二硫键；
(N)与SEQ ID NO:1的第322位对应的位置上的氨基酸残基、以及与SEQ ID NO:1的第356位对应的位置上的氨基酸残基之间形成的二硫键；
(O)与SEQ ID NO:1的第346位对应的位置上的氨基酸残基、以及与SEQ ID NO:1的第393位对应的位置上的氨基酸残基之间形成的二硫键；
(P)与SEQ ID NO:1的第349位对应的位置上的氨基酸残基、以及与SEQ ID NO:1的第390位对应的位置上的氨基酸残基之间形成的二硫键；
条件是：
(C)项和(D)项不同时满足；
(H)项和(J)项不同时满足。
2.如实施方案1所述的热稳定性植酸酶，其中所述突变型大肠杆菌植酸酶与如SEQID NO:1所示的野生型大肠杆菌植酸酶相比，在至少1个下述位置上具有突变：1,25,30,36,37,38,39,46,55,60,62,65,69,70,73,74,75,76,77,79,80,85,101,108,109,111,114,116,118,120,123,126,127,133,137,138,139,141,142,146,151,157,159,161,173,176,178,180,183,184,185,186,187,188,189,204,211,233,235,245,253,255,267,276,282,283,284,286,287,288,291,295,297,311,315,317,318,327,341,354,363,367,369,370,380,382,383,385,391,402,408。
3.如实施方案2所述的热稳定性植酸酶，所述突变型大肠杆菌植酸酶与如SEQ IDNO:1所示的野生型大肠杆菌植酸酶相比，具有至少一个如下突变：Q1S,Q1V,Q1N,A25F,Q30K,A36K,W37F,P38Y,T39D,W46E,I55V,H60S,H60Q,Q62W,R65H,D69N,G70E,A73P,A73D,A73E,K74D,K74P,K74L,K74N,K75C,K75Q,G76T,C77A,Q79L,Q79R,Q79A,Q79G,Q79F,S80P,I85V,A101L,C108A,A109D,A109E,A109G,A109F,A109P,T111S,T111D,T111Q,T114H,T116A,T118R,T118S,S120R,P123E,N126Y,P127V,P127L,C133A,N137V,N137E,N137S,N137P,A138V,A138H,A138D,A138P,N139P,N139A,N139H,T141R,T141E,T141G,T141A,D142R,S146E,S146R,S151P,G157R,G157Q,G157N,G157L,G157A,R159Y,T161P,P173Y,P173S,N176P,N176K,C178A,K183R,Q184S,D185N,D185L,E186V,E186A,S187P,C188A,S189T,N204C,V211W,G233E,G235Y,T245E,Q253V,Y255D,R267A,H282N,P283G,P284T,K286F,Q287Y,A288E,A288R,A288V,V291I,T295I,V297T,G311S,E315G,E315S,N317L,W318Y,T327Y,L341Y,L341V,F354Y,K363A,K363L,S367F,N369P,T370P,A380P,A380R,A380T,C382A,E383S,R385S,R385V,R385T,C391A,E402R,E402T,E402D,E402P,E402N,C408A。
4.如实施方案3所述的热稳定性植酸酶，所述突变型大肠杆菌植酸酶与如SEQ IDNO:1所示的野生型大肠杆菌植酸酶相比，具有选自下组的任一突变组合：W46E,Q62W,A73P,K75C,S146E,R159Y,N204C,Y255D；
A25F,W46E,Q62W,G70E,A73P,K75C,T114H,N137V,D142R,S146E,R159Y,Y255D；
W46E,Q62W,G70E,A73P,K74N,K75Q,G76T,S146E,R159Y,P173S,Y255D,H282N,P283G,P284T；和
A25F,W46E,Q62W,G70E,A73P,K74N,K75Q,T114H,N137V,D142R,S146E,R159Y,P173S,Y255D,H282N,P283G,P284T。
5.如实施方案4所述的热稳定性植酸酶，所述突变型大肠杆菌植酸酶与如SEQ IDNO:1所示的野生型大肠杆菌植酸酶相比，具有选自下组的任一突变组合：
W46E,Q62W,A73P,K75C,S146E,R159Y,N204C,Y255D；
A25F,W46E,Q62W,G70E,A73P,K75C,T114H,N137V,D142R,S146E,R159Y,Y255D；和
W46E,Q62W,G70E,A73P,K74N,K75Q,G76T,S146E,R159Y,P173S,Y255D,H282N,P283G,P284T。
6.如实施方案3所述的热稳定性植酸酶，所述突变型大肠杆菌植酸酶的氨基酸序列为SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:79或SEQ ID NO:99。
7.如实施方案1-6中任一项所述的热稳定性植酸酶，其中，所述二硫键选自(A)、(B)、(C)、(D)、(E)、(J)、(M)或(O)中的至少一项，条件是(C)项和(D)项不同时满足。
8.如实施方案7所述的热稳定性植酸酶，其中，所述氨基酸序列满足下组中的任意两项、三项以上：(A)项、(B)项、(C)项、(D)项、(E)项、(J)项、(M)项和(O)项，条件是(C)项和(D)项不同时满足。
9.如实施方案7所述的热稳定性植酸酶，其中，所述氨基酸序列满足上述(A)项、(B)项、(C)项、(E)项、(J)项或(M)项。
10.如实施方案7所述的热稳定性植酸酶，其中，所述氨基酸序列至少满足上述(D)项或(O)项。
11.如实施方案10所述的热稳定性植酸酶，其中，所述氨基酸序列满足上述(D)项。
12.如实施方案10所述的热稳定性植酸酶，其中，所述氨基酸序列满足上述(O)项。
13.如实施方案7所述的热稳定性植酸酶，其中所述氨基酸序列满足上述(B)项和(O)项；(C)项和(O)项；(D)项和(O)项；(M)项和(O)项；(B)项、(D)项和(O)项；或(D)项、(M)项和(O)项。
14.如实施方案13所述的热稳定性植酸酶，其中，所述氨基酸序列满足上述(B)项和(O)项。
15.如实施方案13所述的热稳定性植酸酶，其中，所述氨基酸序列满足上述(C)项和(O)项。
16.如实施方案13所述的热稳定性植酸酶，其中，所述氨基酸序列满足上述(M)项和(O)项。
17.如实施方案13所述的热稳定性植酸酶，其中，所述氨基酸序列满足上述(B)项、(D)项和(O)项。
18.如实施方案13所述的热稳定性植酸酶，其中，所述氨基酸序列满足上述(D)项、(M)项和(O)项。
19.如实施方案1-18中任一项所述的热稳定性植酸酶，还进一步包含至少一对引入的二硫键，所述二硫键选自：
(i)与SEQ ID NO:1的第31位对应的位置上的氨基酸残基、以及与SEQ ID NO:1的第176位对应的位置上的氨基酸残基之间形成的二硫键；
(ii)与SEQ ID NO:1的第31位对应的位置上的氨基酸残基、以及与SEQ ID NO:1的第177位对应的位置上的氨基酸残基之间形成的二硫键；
(iii)与SEQ ID NO:1的第52位对应的位置上的氨基酸残基、以及与SEQ ID NO:1的第99位对应的位置上的氨基酸残基之间形成的二硫键；
(iv)与SEQ ID NO:1的第59位对应的位置上的氨基酸残基、以及与SEQ ID NO:1的第100位对应的位置上的氨基酸残基之间形成的二硫键；
(v)与SEQ ID NO:1的第91位对应的位置上的氨基酸残基、以及与SEQ ID NO:1的第46位对应的位置上的氨基酸残基之间形成的二硫键；
(vi)与SEQ ID NO:1的第141位对应的位置上的氨基酸残基、以及与SEQ ID NO:1的第200位对应的位置上的氨基酸残基之间形成的二硫键；
(vii)与SEQ ID NO:1的第162位对应的位置上的氨基酸残基、以及与SEQ ID NO:1的第248位对应的位置上的氨基酸残基之间形成的二硫键；
(viii)与SEQ ID NO:1的第205位对应的位置上的氨基酸残基、以及与SEQ ID NO:1的第257位对应的位置上的氨基酸残基之间形成的二硫键；
条件是：(i)项和(ii)项不同时满足。
20.如实施方案1所述的热稳定性植酸酶，其中，该热稳定性植酸酶包含选自下组的任一氨基酸序列：SEQ ID NOs:4-40、SEQ ID NOs:80-88和SEQ ID NOs:100-108。
21.如前述任一项实施方案所述的热稳定性植酸酶，其中，该热稳定性植酸酶是通过在毕赤酵母或者黑曲霉宿主中异源表达而获得的。
22.如前述任一项实施方案所述的热稳定性植酸酶，其中，能够形成二硫键的氨基酸残基为半胱氨酸残基或同型半胱氨酸残基。
23.一种多核苷酸，其编码如实施方案1-22中任一项所述的热稳定性植酸酶。
24.实施方案23的多核苷酸，其编码序列是为在毕赤酵母或者黑曲霉中表达而密码子优化的。
25.实施方案23的多核苷酸，其包含SEQ ID NOs:41-77、SEQ ID NOs:90-98和SEQID NOs:110-118中任一项所示的核苷酸序列。
26.一种宿主细胞，其包含实施方案23-25中任一项所述的多核苷酸。
27.实施方案26所述的宿主细胞，其中该宿主细胞是真菌细胞、细菌细胞或植物细胞。
28.实施方案27所述的宿主细胞，其为酵母细胞或丝状真菌细胞。
29.实施方案28所述的宿主细胞，其为毕赤酵母细胞或者黑曲霉细胞。
30.一种提高植酸酶的热稳定性的方法，其包括对感兴趣的植酸酶的氨基酸序列或其编码核酸序列进行改变，使得植酸酶的氨基酸序列中选自如下(A)至(P)中的至少一项所述的两个位置上的氨基酸残基之间能够形成二硫键：
(A)与SEQ ID NO:1的第34位对应的位置，以及与SEQ ID NO:1的第174位对应的位置；
(B)与SEQ ID NO:1的第56位对应的位置，以及与SEQ ID NO:1的第103位对应的位置；
(C)与SEQ ID NO:1的第57位对应的位置，以及与SEQ ID NO:1的第366位对应的位置；
(D)与SEQ ID NO:1的第61位对应的位置，以及与SEQ ID NO:1的第366位对应的位置；
(E)与SEQ ID NO:1的第82位对应的位置，以及与SEQ ID NO:1的第296位对应的位置；
(F)与SEQ ID NO:1的第128位对应的位置，以及与SEQ ID NO:1的第203位对应的位置；
(G)与SEQ ID NO:1的第140位对应的位置，以及与SEQ ID NO:1的第262位对应的位置；
(H)与SEQ ID NO:1的第156位对应的位置，以及与SEQ ID NO:1的第191位对应的位置；
(I)与SEQ ID NO:1的第165位对应的位置，以及与SEQ ID NO:1的第245位对应的位置；
(J)与SEQ ID NO:1的第191位对应的位置，以及与SEQ ID NO:1的第210位对应的位置；
(K)与SEQ ID NO:1的第196位对应的位置，以及与SEQ ID NO:1的第211位对应的位置；
(L)与SEQ ID NO:1的第264位对应的位置，以及与SEQ ID NO:1的第312位对应的位置；
(M)与SEQ ID NO:1的第315位对应的位置，以及与SEQ ID NO:1的第380位对应的位置；
(N)与SEQ ID NO:1的第322位对应的位置，以及与SEQ ID NO:1的第356位对应的位置；
(O)与SEQ ID NO:1的第346位对应的位置，以及与SEQ ID NO:1的第393位对应的位置；
(P)与SEQ ID NO:1的第349位对应的位置，以及与SEQ ID NO:1的第390位对应的位置；
条件是
(C)项和(D)项不同时被选择；
(H)项和(J)项不同时被选择。
31.如实施方案30所述的方法，其中，所述改变使得感兴趣的植酸酶的氨基酸序列的如(A)项、(B)项、(C)项、(D)项、(E)项、(J)项、(M)项或(O)项中至少一项所述的两个位置上的氨基酸残基之间能够形成二硫键，条件是(C)项和(D)项不同时被选择。
32.如实施方案31所述的方法，其中，所述改变使得所述氨基酸序列的如选自下组的任意两项、三项以上所述的两个位置上的氨基酸残基之间能够形成二硫键：(A)项、(B)项、(C)项、(D)项、(E)项、(J)项、(M)项和(O)项，条件是(C)项和(D)项不同时被选择。
33.如实施方案31所述的方法，其中，所述改变使得所述氨基酸序列的如(A)项、(B)项、(C)项、(E)项、(J)项或(M)项中所述的两个位置上的氨基酸之间能够形成二硫键。
34.如实施方案31所述的方法，其中，所述改变使得所述氨基酸序列的至少如(D)项或(O)项中所述的两个位置上的氨基酸之间能够形成二硫键。
35.如实施方案34所述的方法，其中，所述改变使得所述氨基酸序列的如(D)项所述的两个位置上的氨基酸之间能够形成二硫键。
36.如实施方案34所述的方法，其中，所述改变使得所述氨基酸序列的如(O)项所述的两个位置上的氨基酸之间能够形成二硫键。
37.如实施方案31所述的方法，其中，所述改变使得所述氨基酸序列的如(B)项和(O)项分别所述的两个位置上的氨基酸之间能够形成二硫键。
38.如实施方案31所述的方法，其中，所述改变使得所述氨基酸序列的如(C)项和(O)项分别所述的两个位置上的氨基酸之间能够形成二硫键。
39.如实施方案31所述的方法，其中，所述改变使得所述氨基酸序列的如(M)项和(O)项分别所述的两个位置上的氨基酸之间能够形成二硫键。
40.如实施方案31所述的方法，其中，所述改变使得所述氨基酸序列的如(B)项、(D)和(O)项分别所述的两个位置上的氨基酸之间能够形成二硫键。
41.如实施方案31所述的方法，其中，所述改变使得所述氨基酸序列的如(D)项、(M)和(O)项分别所述的两个位置上的氨基酸之间能够形成二硫键。
42.如实施方案30-41中任一项所述的方法，其中感兴趣的植酸酶来源于大肠杆菌，且包含与SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:79或SEQ ID NO:99所示的氨基酸序列具有至少75％序列一致性的氨基酸序列。
43.如实施方案42所述的方法，其中感兴趣的植酸酶是野生型大肠杆菌植酸酶，优选包含如SEQ ID NO:1所示的氨基酸序列。
44.如实施方案42所述的方法，其中感兴趣的植酸酶是突变型大肠杆菌植酸酶，优选包含如SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:79或SEQ ID NO:99所示的氨基酸序列。
45.如实施方案30-44中任一项所述的方法，其中经过改变后的植酸酶包含选自下组的氨基酸序列、或者其编码核酸包含编码选自下组的氨基酸序列的核苷酸序列：SEQ IDNOs:4-40、SEQ ID NOs:80-88和SEQ ID NOs:100-108。
46.如实施方案30-45中任一项所述的方法，其中该方法还包括生成包含经改造的氨基酸序列的植酸酶，并将其置于容许二硫键形成的环境中。
47.如实施方案46所述的方法，其中生成包含经改造的氨基酸序列的植酸酶包括将编码该植酸酶的多核苷酸在宿主细胞中表达。
48.如实施方案47所述的方法，其中所述宿主细胞是真菌细胞，优选酵母细胞或丝状真菌细胞，更优选毕赤酵母细胞或黑曲霉细胞。
本发明的有益效果：
如本发明所述对植酸酶和突变体引入一对或多对二硫键，尤其是同时引入多对二硫键。本发明在野生型或突变型植酸酶中的引入至少一对二硫键，比野生型植酸酶的残余活力约提高了1-8倍。因此，本发明的技术方案可以提升植酸酶的酶活性质，特别是在于耐热稳定性，耐蒸汽稳定性，制粒稳定性方面，显著优于现有的野生型或者突变型植酸酶；相比于现有的引入二硫键的工程改造植酸酶，其耐热稳定性也有显著提高。
附图说明
图1是pPIC9K-WT质粒图谱。
图2是显示野生型及二硫键突变体热稳定性测定结果的图。
图3是APPA-M1及突变体热稳定性测定结果的图。
图4是APPAan-WT及突变体热稳定性测定结果的图。
图5是APPA-M2及突变体热稳定性测定结果图。
具体实施方式
实施例1构建二硫键突变体，毕赤酵母表达野生型和突变体
大肠杆菌植酸酶3D结构已发布(参见Lim D et al,Nat Struct Biol.2000,7(2):108-13)，根据3D结构文件PDB ID 1DKO作为参考，设计引入如下表所述二硫键。
野生型植酸酶氨基酸序列如SEQ ID NO:1所示，其在毕赤酵母表达核酸序列如SEQID NO:78所示。表达载体为pPIC9K，使用酿酒酵母Alpha因子作为信号肽，野生型植酸酶表达质粒pPIC9K-WT如图1所示。
为构建上表所述突变体，分别设计引物进行PCR，引物如下表所示。
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为引入A-Y的25对二硫键，以质粒pPIC9K-WT为模板，使用F1/R2和F2/R1为引入对，分别进行两个PCR扩增反应，扩增反应使用High-Fidelity DNA聚合酶完成(NewEngland Biolabs，货号M0530L)，参照其说明书进行设置。在扩增完成后，加入DpnI内切酶(New England Biolabs)消化模板，随后使用Gibson/>Master Mix Kit(NewEngland Biolabs，货号E2611)进行片段重组，经测序确认突变体质粒构建成功。突变体质粒按照上表二硫键名称分别命名为pPIC9K-A至pPIC9K-Y。
为了将植酸酶及突变体进行表达，参考Pichia expression kit(Invitrogen)说明书对毕赤酵母GS115和质粒进行操作。具体如下，将毕赤酵母GS115菌株使用YPD培养基(1％酵母提取物、2％蛋白、2％葡萄糖和1.5％琼脂)平板30℃培养48h后，挑取单克隆到4mLYPD液体培养基(1％酵母提取物、2％蛋白、2％葡萄糖)中，30度200RPM培养12h，随后转接到30mLYPD液体培养基的三角瓶中，30℃、220rpm培养4-5h，检测到OD600值在1.1–1.3范围后，将培养液在4度9,000rpm离心2min，分别收集4mL菌体至灭菌EP管中，轻轻弃上清，用灭菌的滤纸吸干残留的上清后用预冷的1mL灭菌水重悬菌体，4℃、9,000rpm离心2min，弃上清。重复上述步骤，将预冷的1mL山梨醇(1mol/L)重悬菌体；4℃、9,000rpm离心2min，弃上清，预冷的100-150μl山梨醇(1mol/L)重悬菌体，至此感受态制备完成。将表达质粒pPIC9K-WT和剩余25个二硫键突变体用BglII进行线性化，线性化片段纯化回收后通过电穿孔法转化上述毕赤酵母GS115感受态中，将混合物均匀涂布于MD平板上，30℃倒置培养2–3天，将平板上所有的菌落都用无菌水洗下来后涂布在含不同浓度遗传霉素的YPD(0.5mg/mL-8mg/mL)平板上筛选多拷贝的转化子。在MD平板上筛选得到毕赤酵母重组菌株命名为APPA-WT和APPA-A，APPA-B,APPA-C,APPA-D,APPA-E,APPA-F,APPA-G,APPA-H,APPA-I,APPA-J,APPA-K,APPA-L,APPA-M,APPA-N,APPA-O,APPA-P,APPA-Q,APPA-R,APPA-S,APPA-T,APPA-U,APPA-V,APPA-W,APPA-X和APPA-Y。将上述筛选获得的克隆分别转接于BMGY培养基中，在30℃、250rpm振荡摇床中培养24h，再转入BMMY培养基中，维持30℃、250rpm条件，每天添加0.5％的甲醇，诱导表达120h后；9000-12000rpm离心10min以去除菌体，得到含植酸酶APPA-WT和其25个突变体的发酵上清液，SDS-PAGE结果显示APPA-S,APPA-X和APPA-Y三个突变体未能表达，剩余的22个突变体都有表达。
实施例2热稳定性测定
植酸酶活力测定遵循GBT 18634-2009文件标准。将实施例1中的23个样品用水稀释至100U/mL。取9mL水于25mL比色管中分别在80℃恒温水浴中预热，用移液枪吸取酶样品1mL，快速加入到各对应试管中，混匀器快速混匀放置3min。迅速冷却至室温，用水进行稀释，测定各样品残余活力。从而计算不同处理温度下的酶活存留率(热处理前酶活定为100％)。热稳定性数据如图2所示，有一些突变体显示出好的热稳定性，APPA-B，APPA-C，APPA-D，APPA-M，APPA-O和APPA-P表现最好，与APPA相比，残余活力提高了20-25％左右，提高了约2-3倍。上述结果表明二硫键的引入对突变体有显著影响，有的突变甚至导致了不能正常表达，如APPA-S,APPA-X和APPA-Y；另外一些特定二硫键引入会导致稳定性降低，如APPA-Q和APPA-V，上述两个突变体导致了显著低于野生型的热稳定性；还有一些引入的二硫键对于酶结构稳定是有利的，如APPA-A至APPA-P，能够提高野生型的抗热能力。
实施例3突变体基础上引入二硫键及测定其稳定性
Nov9X是野生型植酸酶经突变筛选获得的耐热优良突变体(如US7432098所述)，其在野生型基础上引入8个突变，具体序列如SEQ ID NO:2所示。在Nov9X序列基础上继续引入其他突变，其序列变为SEQ ID NO:3所述，命名为APPA-M1，可以进一步提高其热稳定性。为了测试实施例1中描述的二硫键突变体是否在植酸酶突变体上也可以发挥功能，进一步提高稳定性。按照实施例1中的方法在APPA-M1基础上引入二硫键D，O，以及二硫键组合B+O，C+O，D+O，M+O，B+D+O和D+M+O，各突变体分别命名为APPA-M1-D，APPA-M1-O，APPA-M1-BO，APPA-M1-CO，APPA-M1-DO，APPA-M1-MO，APPA-M1-BDO和APPA-M1-DMO。同时根据US20170240872和US20130017185描述，在APPA-M1基础上引入各自实施例中最好的两个突变体二硫键，分别命名为US20170240872-A，US20170240872-B，US20130017185-B和US20130017185-C。使用毕赤酵母表达各突变体，随后按照实施例2中的方法测定热稳定性，不同参数在于85度条件下孵育3分钟。结果如图3所示，二硫键D和O都进一步提高了突变体的热稳定性，而二硫键O对于APPA-M1突变体稳定性提高要比野生型APPA-WT提高更加有效，提高幅度高达35.5％。组合引入二硫键突变体APPA-M1-CO和APPA-M1-DO都表现出了与APPA-M1-O相似的稳定性，其他组合突变，如APPA-M1-BO、APPA-M1-MO、APPA-M1-BDO和APPA-M1-DMO则具有更高的稳定性，最好的APPA-M1-BO残余活力可达到77.2％，比APPA-M1提高了约1-1.5倍，具有显著的耐热特性，可以预见其在饲料制粒中会有良好表现，上述结果显示出合适的组合可以创造出更稳定的突变体。在本方法下测定的US20170240872-A和US20170240872-B稳定性比APPA-M1提高1.1-8.7％，US20130017185-B和US20130017185-C稳定性提高5.0-14.8％，可以看到，发明人所提出的二硫键引入显示出更加有效的结果。
实施例4黑曲霉表达大肠杆菌野生型植酸酶和引入二硫键突变体植酸酶
按照专利申请CN107353327的描述对大肠杆菌植酸酶野生型(SEQ ID NO:1)及突变体(A到P)进行表达，野生型植酸酶命名为APPAan-WT，各突变体分别按照APPAan-A到APPAan-P进行命名。获得摇瓶上清液后按照实施例2描述进行热稳定性测定，不同参数在于85度条件下孵育3分钟。实验结果如图4所示。我们发现黑曲霉表达的野生型植酸酶较毕赤酵母表达的酶体现出明显的稳定性，这可能是由于他们的糖基化状态不同造成的。实验还发现突变体APPAan-P不能够表达，APPAan-G表现出和WT差不多的稳定性，而APPAan-H稳定性显著下降。剩余的13个突变体都表现出显著的稳定性性能提升，都表现出最低5％最高20.5％的提升。我们还发现稳定性提高的幅度与毕赤酵母中表达的突变体并不一致。上述结果表明，16个突变体至少在一种宿主细胞中表达并体现出比野生型较为优秀的稳定性，而合适地引入上述二硫键组合可以获得更高稳定性的突变体。
实施例5植酸酶突变体引入二硫键后稳定性检测结果
Nov9X是野生型植酸酶经突变筛选获得的耐热优良突变体(如US7432098所述)，其在野生型基础上引入8个突变，具体序列如SEQ ID NO:2所示。在Nov9X序列基础上，根据文献报道(Improving specific activity and thermostability of Escherichia coliphytase by structure-based rational design)继续引入糖基化位点，其序列变为SEQID NO:79所述，命名为APPA-M2，可以进一步提高其热稳定性。为了测试实施例1中描述的二硫键突变体是否在植酸酶突变体APPA-M2上也可以发挥功能，进一步提高稳定性。按照实施例1中的方法在APPA-M2基础上引入二硫键B，C，D，M，O以及二硫键组合B+O，D+O，M+O，C+O，各突变体分别命名为APPA-M2-B，APPA-M2-C，APPA-M2-D，APPA-M2-M，APPA-M2-O，APPA-M2-BO，APPA-M2-DO,APPA-M2-MO和APPA-M2-CO。各突变体的氨基酸序列如SEQ ID NOs:80-88所示，对应的核苷酸序列如SEQ ID NOs:90-98所示。使用黑曲霉表达各突变体，随后按照实施例2中的方法测定热稳定性。结果如图5所示，该实验中采用的二硫键都显著的提高了突变体的热稳定性，其中组合二硫键C+O效果最佳，其耐热处理后残余活力可达到84.5％，具有显著的耐热特性，可以预见其在饲料制粒中会有良好表现，上述结果显示出合适的组合可以创造出更稳定的突变体。上述结果显示，发明人所提出的二硫键的引入对植酸酶突变体序列依旧显示出非常有效的结果。
发明人也尝试了在Nov9X序列基础上，继续引入糖基化位点，其序列如SEQ ID NO:99所示，命名为APPA-M3，也可以提高其热稳定性。按照实施例1中的方法在APPA-M3基础上引入二硫键B，C，D，M，O以及二硫键组合B+O，D+O，M+O，C+O，各突变体分别命名为APPA-M3-B，APPA-M3-C，APPA-M3-D，APPA-M3-M，APPA-M3-O，APPA-M3-BO，APPA-M3-DO,APPA-M3-MO和APPA-M3-CO。各突变体的氨基酸序列如SEQ ID NOs:100-108所示，对应的核苷酸序列如SEQID NOs:110-118所示。使用黑曲霉表达各突变体，按照实施例2中的方法测定稳定性，发现引入二硫键的突变体与AMMA-M2引入二硫键的突变体一样，具有较好的耐热特性，同样可以预见其在饲料制粒中会有良好的表现。
本发明所述方法的各种修饰和变型对于本领域技术人员是显而易见的，并不脱离本发明的范围。尽管本发明结合特定实施方案进行了描述，应当理解的是，要求保护的本发明并未不恰当地限定于这些特定优选实施方案。事实上，对本领域技术人员显而易见的用于实现本发明的所述技术效果的野生型植酸酶的各种突变修饰都包含在权利要求的范围内。
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65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Cys Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His Thr Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Asn Ala Asn Val Thr Asp Ala Ile
130 135 140
Leu Ser Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Arg Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Pro Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Tyr Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro His Pro Pro Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Glu Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Gln Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Leu Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Ala Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Leu Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 6
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPA-C
<400> 6
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Ala Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Trp Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Ala Cys Leu Gly His Tyr Gln Arg Gln
50 55 60
Arg Leu Val Ala Asp Gly Leu Leu Ala Lys Lys Gly Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Gly Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His Thr Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Asn Ala Asn Val Thr Asp Ala Ile
130 135 140
Leu Ser Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Arg Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Pro Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Tyr Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro His Pro Pro Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Glu Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Gln Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Cys Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Ala Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Leu Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 7
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPA-D
<400> 7
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Ala Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Trp Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Ala Tyr Leu Gly His Cys Gln Arg Gln
50 55 60
Arg Leu Val Ala Asp Gly Leu Leu Ala Lys Lys Gly Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Gly Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His Thr Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Asn Ala Asn Val Thr Asp Ala Ile
130 135 140
Leu Ser Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Arg Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Pro Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Tyr Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro His Pro Pro Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Glu Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Gln Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Cys Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Ala Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Leu Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 8
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPA-E
<400> 8
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Ala Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Trp Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Ala Tyr Leu Gly His Tyr Gln Arg Gln
50 55 60
Arg Leu Val Ala Asp Gly Leu Leu Ala Lys Lys Gly Cys Pro Gln Ser
65 70 75 80
Gly Cys Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Gly Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His Thr Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Asn Ala Asn Val Thr Asp Ala Ile
130 135 140
Leu Ser Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Arg Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Pro Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Tyr Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro His Pro Pro Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Cys Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Glu Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Gln Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Leu Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Ala Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Leu Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 9
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPA-F
<400> 9
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Ala Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Trp Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Ala Tyr Leu Gly His Tyr Gln Arg Gln
50 55 60
Arg Leu Val Ala Asp Gly Leu Leu Ala Lys Lys Gly Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Gly Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His Thr Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Cys
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Asn Ala Asn Val Thr Asp Ala Ile
130 135 140
Leu Ser Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Arg Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Pro Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Cys Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Tyr Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro His Pro Pro Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Glu Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Gln Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Leu Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Ala Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Leu Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 10
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPA-G
<400> 10
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Ala Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Trp Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Ala Tyr Leu Gly His Tyr Gln Arg Gln
50 55 60
Arg Leu Val Ala Asp Gly Leu Leu Ala Lys Lys Gly Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Gly Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His Thr Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Asn Ala Asn Cys Thr Asp Ala Ile
130 135 140
Leu Ser Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Arg Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Pro Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Tyr Leu
245 250 255
Leu Gln Arg Thr Pro Cys Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro His Pro Pro Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Glu Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Gln Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Leu Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Ala Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Leu Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 11
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPA-H
<400> 11
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Ala Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Trp Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Ala Tyr Leu Gly His Tyr Gln Arg Gln
50 55 60
Arg Leu Val Ala Asp Gly Leu Leu Ala Lys Lys Gly Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Gly Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His Thr Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Asn Ala Asn Val Thr Asp Ala Ile
130 135 140
Leu Ser Arg Ala Gly Gly Ser Ile Ala Asp Phe Cys Gly His Arg Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Pro Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Cys Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Tyr Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro His Pro Pro Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Glu Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Gln Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Leu Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Ala Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Leu Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 12
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPA-I
<400> 12
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Ala Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Trp Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Ala Tyr Leu Gly His Tyr Gln Arg Gln
50 55 60
Arg Leu Val Ala Asp Gly Leu Leu Ala Lys Lys Gly Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Gly Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His Thr Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Asn Ala Asn Val Thr Asp Ala Ile
130 135 140
Leu Ser Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Arg Gln
145 150 155 160
Thr Ala Phe Arg Cys Leu Glu Arg Val Leu Asn Phe Pro Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Cys Leu Leu Ser Leu His Asn Ala Gln Phe Tyr Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro His Pro Pro Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Glu Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Gln Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Leu Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Ala Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Leu Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 13
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPA-J
<400> 13
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Ala Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Trp Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Ala Tyr Leu Gly His Tyr Gln Arg Gln
50 55 60
Arg Leu Val Ala Asp Gly Leu Leu Ala Lys Lys Gly Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Gly Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His Thr Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Asn Ala Asn Val Thr Asp Ala Ile
130 135 140
Leu Ser Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Arg Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Pro Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Cys Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Cys Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Tyr Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro His Pro Pro Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Glu Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Gln Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Leu Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Ala Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Leu Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 14
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPA-K
<400> 14
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Ala Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Trp Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Ala Tyr Leu Gly His Tyr Gln Arg Gln
50 55 60
Arg Leu Val Ala Asp Gly Leu Leu Ala Lys Lys Gly Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Gly Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His Thr Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Asn Ala Asn Val Thr Asp Ala Ile
130 135 140
Leu Ser Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Arg Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Pro Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Cys Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Cys Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Tyr Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro His Pro Pro Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Glu Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Gln Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Leu Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Ala Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Leu Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 15
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPA-L
<400> 15
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Ala Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Trp Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Ala Tyr Leu Gly His Tyr Gln Arg Gln
50 55 60
Arg Leu Val Ala Asp Gly Leu Leu Ala Lys Lys Gly Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Gly Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His Thr Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Asn Ala Asn Val Thr Asp Ala Ile
130 135 140
Leu Ser Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Arg Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Pro Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Tyr Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Cys Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro His Pro Pro Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Cys Ala Leu Glu Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Gln Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Leu Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Ala Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Leu Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 16
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPA-M
<400> 16
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Ala Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Trp Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Ala Tyr Leu Gly His Tyr Gln Arg Gln
50 55 60
Arg Leu Val Ala Asp Gly Leu Leu Ala Lys Lys Gly Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Gly Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His Thr Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Asn Ala Asn Val Thr Asp Ala Ile
130 135 140
Leu Ser Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Arg Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Pro Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Tyr Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro His Pro Pro Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Cys Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Gln Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Leu Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Cys Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Leu Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 17
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPA-N
<400> 17
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Ala Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Trp Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Ala Tyr Leu Gly His Tyr Gln Arg Gln
50 55 60
Arg Leu Val Ala Asp Gly Leu Leu Ala Lys Lys Gly Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Gly Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His Thr Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Asn Ala Asn Val Thr Asp Ala Ile
130 135 140
Leu Ser Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Arg Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Pro Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Tyr Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro His Pro Pro Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Glu Leu Asn Trp Thr Leu
305 310 315 320
Pro Cys Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Gln Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Cys Leu Gln Gln Met Arg Asp Lys Thr Pro Leu Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Ala Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Leu Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 18
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPA-O
<400> 18
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Ala Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Trp Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Ala Tyr Leu Gly His Tyr Gln Arg Gln
50 55 60
Arg Leu Val Ala Asp Gly Leu Leu Ala Lys Lys Gly Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Gly Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His Thr Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Asn Ala Asn Val Thr Asp Ala Ile
130 135 140
Leu Ser Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Arg Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Pro Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Tyr Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro His Pro Pro Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Glu Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Cys Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Leu Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Ala Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Cys Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 19
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPA-P
<400> 19
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Ala Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Trp Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Ala Tyr Leu Gly His Tyr Gln Arg Gln
50 55 60
Arg Leu Val Ala Asp Gly Leu Leu Ala Lys Lys Gly Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Gly Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His Thr Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Asn Ala Asn Val Thr Asp Ala Ile
130 135 140
Leu Ser Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Arg Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Pro Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Tyr Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro His Pro Pro Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Glu Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Gln Trp Ile Cys Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Leu Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Ala Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Cys Cys Ser Leu Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 20
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPA-M1-D
<400> 20
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Phe Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Glu Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Ala Tyr Leu Gly His Cys Trp Arg Gln
50 55 60
Arg Leu Val Ala Asp Glu Leu Leu Pro Lys Cys Gly Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Gly Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His His Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Val Ala Asn Val Thr Arg Ala Ile
130 135 140
Leu Glu Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Tyr Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Pro Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Asp Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro His Pro Pro Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Glu Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Gln Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Cys Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Ala Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Leu Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 21
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPA-M1-O
<400> 21
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Phe Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Glu Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Ala Tyr Leu Gly His Tyr Trp Arg Gln
50 55 60
Arg Leu Val Ala Asp Glu Leu Leu Pro Lys Cys Gly Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Gly Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His His Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Val Ala Asn Val Thr Arg Ala Ile
130 135 140
Leu Glu Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Tyr Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Pro Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Asp Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro His Pro Pro Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Glu Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Cys Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Leu Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Ala Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Cys Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 22
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPA-M1-BO
<400> 22
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Phe Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Glu Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Cys Tyr Leu Gly His Tyr Trp Arg Gln
50 55 60
Arg Leu Val Ala Asp Glu Leu Leu Pro Lys Cys Gly Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Cys Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His His Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Val Ala Asn Val Thr Arg Ala Ile
130 135 140
Leu Glu Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Tyr Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Pro Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Asp Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro His Pro Pro Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Glu Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Cys Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Leu Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Ala Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Cys Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 23
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPA-M1-CO
<400> 23
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Phe Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Glu Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Ala Cys Leu Gly His Tyr Trp Arg Gln
50 55 60
Arg Leu Val Ala Asp Glu Leu Leu Pro Lys Cys Gly Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Gly Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His His Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Val Ala Asn Val Thr Arg Ala Ile
130 135 140
Leu Glu Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Tyr Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Pro Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Asp Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro His Pro Pro Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Glu Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Cys Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Cys Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Ala Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Cys Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 24
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPA-M1-DO
<400> 24
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Phe Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Glu Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Ala Tyr Leu Gly His Cys Trp Arg Gln
50 55 60
Arg Leu Val Ala Asp Glu Leu Leu Pro Lys Cys Gly Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Gly Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His His Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Val Ala Asn Val Thr Arg Ala Ile
130 135 140
Leu Glu Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Tyr Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Pro Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Asp Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro His Pro Pro Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Glu Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Cys Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Cys Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Ala Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Cys Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 25
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPA-M1-MO
<400> 25
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Phe Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Glu Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Ala Tyr Leu Gly His Tyr Trp Arg Gln
50 55 60
Arg Leu Val Ala Asp Glu Leu Leu Pro Lys Cys Gly Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Gly Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His His Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Val Ala Asn Val Thr Arg Ala Ile
130 135 140
Leu Glu Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Tyr Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Pro Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Asp Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro His Pro Pro Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Cys Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Cys Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Leu Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Cys Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Cys Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 26
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPA-M1-BDO
<400> 26
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Phe Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Glu Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Cys Tyr Leu Gly His Cys Trp Arg Gln
50 55 60
Arg Leu Val Ala Asp Glu Leu Leu Pro Lys Cys Gly Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Cys Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His His Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Val Ala Asn Val Thr Arg Ala Ile
130 135 140
Leu Glu Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Tyr Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Pro Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Asp Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro His Pro Pro Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Glu Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Cys Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Cys Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Ala Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Cys Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 27
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPA-M1-DMO
<400> 27
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Phe Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Glu Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Ala Tyr Leu Gly His Cys Trp Arg Gln
50 55 60
Arg Leu Val Ala Asp Glu Leu Leu Pro Lys Cys Gly Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Gly Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His His Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Val Ala Asn Val Thr Arg Ala Ile
130 135 140
Leu Glu Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Tyr Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Pro Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Asp Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro His Pro Pro Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Cys Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Cys Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Cys Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Cys Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Cys Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 28
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPAan-A
<400> 28
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Ala Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Cys Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Trp Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Ala Tyr Leu Gly His Tyr Gln Arg Gln
50 55 60
Arg Leu Val Ala Asp Gly Leu Leu Ala Lys Lys Gly Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Gly Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His Thr Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Asn Ala Asn Val Thr Asp Ala Ile
130 135 140
Leu Ser Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Arg Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Pro Cys Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Tyr Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro His Pro Pro Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Glu Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Gln Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Leu Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Ala Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Leu Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 29
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPAan-B
<400> 29
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Ala Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Trp Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Cys Tyr Leu Gly His Tyr Gln Arg Gln
50 55 60
Arg Leu Val Ala Asp Gly Leu Leu Ala Lys Lys Gly Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Cys Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His Thr Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Asn Ala Asn Val Thr Asp Ala Ile
130 135 140
Leu Ser Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Arg Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Pro Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Tyr Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro His Pro Pro Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Glu Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Gln Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Leu Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Ala Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Leu Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 30
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPAan-C
<400> 30
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Ala Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Trp Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Ala Cys Leu Gly His Tyr Gln Arg Gln
50 55 60
Arg Leu Val Ala Asp Gly Leu Leu Ala Lys Lys Gly Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Gly Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His Thr Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Asn Ala Asn Val Thr Asp Ala Ile
130 135 140
Leu Ser Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Arg Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Pro Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Tyr Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro His Pro Pro Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Glu Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Gln Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Cys Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Ala Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Leu Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 31
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPAan-D
<400> 31
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Ala Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Trp Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Ala Tyr Leu Gly His Cys Gln Arg Gln
50 55 60
Arg Leu Val Ala Asp Gly Leu Leu Ala Lys Lys Gly Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Gly Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His Thr Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Asn Ala Asn Val Thr Asp Ala Ile
130 135 140
Leu Ser Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Arg Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Pro Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Tyr Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro His Pro Pro Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Glu Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Gln Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Cys Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Ala Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Leu Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 32
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPAan-E
<400> 32
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Ala Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Trp Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Ala Tyr Leu Gly His Tyr Gln Arg Gln
50 55 60
Arg Leu Val Ala Asp Gly Leu Leu Ala Lys Lys Gly Cys Pro Gln Ser
65 70 75 80
Gly Cys Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Gly Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His Thr Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Asn Ala Asn Val Thr Asp Ala Ile
130 135 140
Leu Ser Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Arg Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Pro Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Tyr Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro His Pro Pro Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Cys Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Glu Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Gln Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Leu Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Ala Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Leu Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 33
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPAan-F
<400> 33
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Ala Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Trp Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Ala Tyr Leu Gly His Tyr Gln Arg Gln
50 55 60
Arg Leu Val Ala Asp Gly Leu Leu Ala Lys Lys Gly Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Gly Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His Thr Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Cys
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Asn Ala Asn Val Thr Asp Ala Ile
130 135 140
Leu Ser Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Arg Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Pro Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Cys Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Tyr Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro His Pro Pro Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Glu Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Gln Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Leu Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Ala Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Leu Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 34
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPAan-I
<400> 34
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Ala Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Trp Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Ala Tyr Leu Gly His Tyr Gln Arg Gln
50 55 60
Arg Leu Val Ala Asp Gly Leu Leu Ala Lys Lys Gly Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Gly Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His Thr Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Asn Ala Asn Val Thr Asp Ala Ile
130 135 140
Leu Ser Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Arg Gln
145 150 155 160
Thr Ala Phe Arg Cys Leu Glu Arg Val Leu Asn Phe Pro Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Cys Leu Leu Ser Leu His Asn Ala Gln Phe Tyr Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro His Pro Pro Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Glu Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Gln Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Leu Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Ala Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Leu Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 35
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPAan-J
<400> 35
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Ala Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Trp Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Ala Tyr Leu Gly His Tyr Gln Arg Gln
50 55 60
Arg Leu Val Ala Asp Gly Leu Leu Ala Lys Lys Gly Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Gly Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His Thr Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Asn Ala Asn Val Thr Asp Ala Ile
130 135 140
Leu Ser Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Arg Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Pro Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Cys Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Cys
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Tyr Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro His Pro Pro Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Glu Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Gln Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Leu Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Ala Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Leu Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 36
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPAan-K
<400> 36
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Ala Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Trp Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Ala Tyr Leu Gly His Tyr Gln Arg Gln
50 55 60
Arg Leu Val Ala Asp Gly Leu Leu Ala Lys Lys Gly Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Gly Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His Thr Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Asn Ala Asn Val Thr Asp Ala Ile
130 135 140
Leu Ser Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Arg Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Pro Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Cys Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Cys Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Tyr Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro His Pro Pro Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Glu Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Gln Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Leu Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Ala Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Leu Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 37
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPAan-L
<400> 37
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Ala Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Trp Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Ala Tyr Leu Gly His Tyr Gln Arg Gln
50 55 60
Arg Leu Val Ala Asp Gly Leu Leu Ala Lys Lys Gly Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Gly Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His Thr Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Asn Ala Asn Val Thr Asp Ala Ile
130 135 140
Leu Ser Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Arg Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Pro Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Tyr Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Cys Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro His Pro Pro Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Cys Ala Leu Glu Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Gln Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Leu Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Ala Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Leu Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 38
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPAan-M
<400> 38
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Ala Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Trp Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Ala Tyr Leu Gly His Tyr Gln Arg Gln
50 55 60
Arg Leu Val Ala Asp Gly Leu Leu Ala Lys Lys Gly Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Gly Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His Thr Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Asn Ala Asn Val Thr Asp Ala Ile
130 135 140
Leu Ser Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Arg Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Pro Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Tyr Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro His Pro Pro Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Cys Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Gln Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Leu Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Cys Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Leu Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 39
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPAan-N
<400> 39
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Ala Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Trp Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Ala Tyr Leu Gly His Tyr Gln Arg Gln
50 55 60
Arg Leu Val Ala Asp Gly Leu Leu Ala Lys Lys Gly Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Gly Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His Thr Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Asn Ala Asn Val Thr Asp Ala Ile
130 135 140
Leu Ser Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Arg Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Pro Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Tyr Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro His Pro Pro Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Glu Leu Asn Trp Thr Leu
305 310 315 320
Pro Cys Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Gln Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Cys Leu Gln Gln Met Arg Asp Lys Thr Pro Leu Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Ala Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Leu Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 40
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPAan-O
<400> 40
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Ala Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Trp Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Ala Tyr Leu Gly His Tyr Gln Arg Gln
50 55 60
Arg Leu Val Ala Asp Gly Leu Leu Ala Lys Lys Gly Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Gly Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His Thr Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Asn Ala Asn Val Thr Asp Ala Ile
130 135 140
Leu Ser Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Arg Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Pro Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Tyr Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro His Pro Pro Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Glu Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Cys Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Leu Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Ala Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Cys Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 41
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPA-A
<400> 41
cagagtgagc ctgagttgaa actggaatcc gttgtcatcg tctctagaca tggtgttaga 60
gcaccaacca aggccaccca acttatgcaa gatgtcacct gtgacgcttg gccaacctgg 120
ccagtcaagc tgggttggtt gacacctaga ggtggtgagc tcattgctta cttgggtcac 180
taccaaagac agcgtcttgt tgccgacgga ttgttggcca agaagggttg tccacaatct 240
ggtcaagtag ctattattgc tgacgtcgac gaaagaaccc gtaagacagg tgaagccttc 300
gccgccggtc ttgctcctga ctgtgccatt accgttcaca cccaagctga cacttcttct 360
ccagatccat tgttcaaccc tttgaagact ggtgtttgcc aattggacaa cgctaacgtt 420
actgacgcta tcttgtccag agctggagga tccattgctg acttcaccgg tcacagacag 480
actgccttca gagagttgga aagagttctt aacttcccat gttcaaactt gtgcttgaag 540
cgtgagaagc aagacgaatc ctgttccttg actcaagcat taccatctga gttgaaggtc 600
tccgccgaca acgtctcttt gaccggtgct gtcagcttgg cttccatgtt gactgaaatc 660
tttcttctgc aacaagctca aggtatgcct gagccaggtt ggggtagaat caccgactct 720
caccaatgga acaccttgtt gtccttgcac aacgctcaat tctacttgct gcagagaact 780
ccagaggttg ctagatccag agccacccca ttgttggact tgatcaagac tgctttgact 840
cctcacccac ctcaaaagca agcctacggt gttaccttgc ccacttctgt cttgttcatt 900
gccggtcacg atactaactt ggcaaatctc ggcggtgctt tggagttgaa ctggactctt 960
cctggtcaac ctgataacac tccaccaggt ggtgagctcg ttttcgaaag atggcgtaga 1020
ctatctgata actctcaatg gattcaggtt tcgttggtct tccaaacttt gcagcagatg 1080
agagacaaga ctccactgtc tttgaacacg cctccaggag aagtcaaatt gaccttggct 1140
ggatgtgaag agagaaatgc tcagggtatg tgttccttgg ctggtttcac tcaaatcgtt 1200
aacgaagcta gaatcccagc ttgttccttg tag 1233
<210> 42
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPA-B
<400> 42
cagagtgagc ctgagttgaa actggaatcc gttgtcatcg tctctagaca tggtgttaga 60
gcaccaacca aggccaccca acttatgcaa gatgtcaccc cagacgcttg gccaacctgg 120
ccagtcaagc tgggttggtt gacacctaga ggtggtgagc tcatttgtta cttgggtcac 180
taccaaagac agcgtcttgt tgccgacgga ttgttggcca agaagggttg tccacaatct 240
ggtcaagtag ctattattgc tgacgtcgac gaaagaaccc gtaagacagg tgaagccttc 300
gccgcctgtc ttgctcctga ctgtgccatt accgttcaca cccaagctga cacttcttct 360
ccagatccat tgttcaaccc tttgaagact ggtgtttgcc aattggacaa cgctaacgtt 420
actgacgcta tcttgtccag agctggagga tccattgctg acttcaccgg tcacagacag 480
actgccttca gagagttgga aagagttctt aacttcccac aatcaaactt gtgcttgaag 540
cgtgagaagc aagacgaatc ctgttccttg actcaagcat taccatctga gttgaaggtc 600
tccgccgaca acgtctcttt gaccggtgct gtcagcttgg cttccatgtt gactgaaatc 660
tttcttctgc aacaagctca aggtatgcct gagccaggtt ggggtagaat caccgactct 720
caccaatgga acaccttgtt gtccttgcac aacgctcaat tctacttgct gcagagaact 780
ccagaggttg ctagatccag agccacccca ttgttggact tgatcaagac tgctttgact 840
cctcacccac ctcaaaagca agcctacggt gttaccttgc ccacttctgt cttgttcatt 900
gccggtcacg atactaactt ggcaaatctc ggcggtgctt tggagttgaa ctggactctt 960
cctggtcaac ctgataacac tccaccaggt ggtgagctcg ttttcgaaag atggcgtaga 1020
ctatctgata actctcaatg gattcaggtt tcgttggtct tccaaacttt gcagcagatg 1080
agagacaaga ctccactgtc tttgaacacg cctccaggag aagtcaaatt gaccttggct 1140
ggatgtgaag agagaaatgc tcagggtatg tgttccttgg ctggtttcac tcaaatcgtt 1200
aacgaagcta gaatcccagc ttgttccttg tag 1233
<210> 43
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPA-C
<400> 43
cagagtgagc ctgagttgaa actggaatcc gttgtcatcg tctctagaca tggtgttaga 60
gcaccaacca aggccaccca acttatgcaa gatgtcaccc cagacgcttg gccaacctgg 120
ccagtcaagc tgggttggtt gacacctaga ggtggtgagc tcattgcttg tttgggtcac 180
taccaaagac agcgtcttgt tgccgacgga ttgttggcca agaagggttg tccacaatct 240
ggtcaagtag ctattattgc tgacgtcgac gaaagaaccc gtaagacagg tgaagccttc 300
gccgccggtc ttgctcctga ctgtgccatt accgttcaca cccaagctga cacttcttct 360
ccagatccat tgttcaaccc tttgaagact ggtgtttgcc aattggacaa cgctaacgtt 420
actgacgcta tcttgtccag agctggagga tccattgctg acttcaccgg tcacagacag 480
actgccttca gagagttgga aagagttctt aacttcccac aatcaaactt gtgcttgaag 540
cgtgagaagc aagacgaatc ctgttccttg actcaagcat taccatctga gttgaaggtc 600
tccgccgaca acgtctcttt gaccggtgct gtcagcttgg cttccatgtt gactgaaatc 660
tttcttctgc aacaagctca aggtatgcct gagccaggtt ggggtagaat caccgactct 720
caccaatgga acaccttgtt gtccttgcac aacgctcaat tctacttgct gcagagaact 780
ccagaggttg ctagatccag agccacccca ttgttggact tgatcaagac tgctttgact 840
cctcacccac ctcaaaagca agcctacggt gttaccttgc ccacttctgt cttgttcatt 900
gccggtcacg atactaactt ggcaaatctc ggcggtgctt tggagttgaa ctggactctt 960
cctggtcaac ctgataacac tccaccaggt ggtgagctcg ttttcgaaag atggcgtaga 1020
ctatctgata actctcaatg gattcaggtt tcgttggtct tccaaacttt gcagcagatg 1080
agagacaaga ctccatgttc tttgaacacg cctccaggag aagtcaaatt gaccttggct 1140
ggatgtgaag agagaaatgc tcagggtatg tgttccttgg ctggtttcac tcaaatcgtt 1200
aacgaagcta gaatcccagc ttgttccttg tag 1233
<210> 44
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPA-D
<400> 44
cagagtgagc ctgagttgaa actggaatcc gttgtcatcg tctctagaca tggtgttaga 60
gcaccaacca aggccaccca acttatgcaa gatgtcaccc cagacgcttg gccaacctgg 120
ccagtcaagc tgggttggtt gacacctaga ggtggtgagc tcattgctta cttgggtcac 180
tgtcaaagac agcgtcttgt tgccgacgga ttgttggcca agaagggttg tccacaatct 240
ggtcaagtag ctattattgc tgacgtcgac gaaagaaccc gtaagacagg tgaagccttc 300
gccgccggtc ttgctcctga ctgtgccatt accgttcaca cccaagctga cacttcttct 360
ccagatccat tgttcaaccc tttgaagact ggtgtttgcc aattggacaa cgctaacgtt 420
actgacgcta tcttgtccag agctggagga tccattgctg acttcaccgg tcacagacag 480
actgccttca gagagttgga aagagttctt aacttcccac aatcaaactt gtgcttgaag 540
cgtgagaagc aagacgaatc ctgttccttg actcaagcat taccatctga gttgaaggtc 600
tccgccgaca acgtctcttt gaccggtgct gtcagcttgg cttccatgtt gactgaaatc 660
tttcttctgc aacaagctca aggtatgcct gagccaggtt ggggtagaat caccgactct 720
caccaatgga acaccttgtt gtccttgcac aacgctcaat tctacttgct gcagagaact 780
ccagaggttg ctagatccag agccacccca ttgttggact tgatcaagac tgctttgact 840
cctcacccac ctcaaaagca agcctacggt gttaccttgc ccacttctgt cttgttcatt 900
gccggtcacg atactaactt ggcaaatctc ggcggtgctt tggagttgaa ctggactctt 960
cctggtcaac ctgataacac tccaccaggt ggtgagctcg ttttcgaaag atggcgtaga 1020
ctatctgata actctcaatg gattcaggtt tcgttggtct tccaaacttt gcagcagatg 1080
agagacaaga ctccatgttc tttgaacacg cctccaggag aagtcaaatt gaccttggct 1140
ggatgtgaag agagaaatgc tcagggtatg tgttccttgg ctggtttcac tcaaatcgtt 1200
aacgaagcta gaatcccagc ttgttccttg tag 1233
<210> 45
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPA-E
<400> 45
cagagtgagc ctgagttgaa actggaatcc gttgtcatcg tctctagaca tggtgttaga 60
gcaccaacca aggccaccca acttatgcaa gatgtcaccc cagacgcttg gccaacctgg 120
ccagtcaagc tgggttggtt gacacctaga ggtggtgagc tcattgctta cttgggtcac 180
taccaaagac agcgtcttgt tgccgacgga ttgttggcca agaagggttg tccacaatct 240
ggttgtgtag ctattattgc tgacgtcgac gaaagaaccc gtaagacagg tgaagccttc 300
gccgccggtc ttgctcctga ctgtgccatt accgttcaca cccaagctga cacttcttct 360
ccagatccat tgttcaaccc tttgaagact ggtgtttgcc aattggacaa cgctaacgtt 420
actgacgcta tcttgtccag agctggagga tccattgctg acttcaccgg tcacagacag 480
actgccttca gagagttgga aagagttctt aacttcccac aatcaaactt gtgcttgaag 540
cgtgagaagc aagacgaatc ctgttccttg actcaagcat taccatctga gttgaaggtc 600
tccgccgaca acgtctcttt gaccggtgct gtcagcttgg cttccatgtt gactgaaatc 660
tttcttctgc aacaagctca aggtatgcct gagccaggtt ggggtagaat caccgactct 720
caccaatgga acaccttgtt gtccttgcac aacgctcaat tctacttgct gcagagaact 780
ccagaggttg ctagatccag agccacccca ttgttggact tgatcaagac tgctttgact 840
cctcacccac ctcaaaagca agcctacggt gttaccttgc ccacttgtgt cttgttcatt 900
gccggtcacg atactaactt ggcaaatctc ggcggtgctt tggagttgaa ctggactctt 960
cctggtcaac ctgataacac tccaccaggt ggtgagctcg ttttcgaaag atggcgtaga 1020
ctatctgata actctcaatg gattcaggtt tcgttggtct tccaaacttt gcagcagatg 1080
agagacaaga ctccactgtc tttgaacacg cctccaggag aagtcaaatt gaccttggct 1140
ggatgtgaag agagaaatgc tcagggtatg tgttccttgg ctggtttcac tcaaatcgtt 1200
aacgaagcta gaatcccagc ttgttccttg tag 1233
<210> 46
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPA-F
<400> 46
cagagtgagc ctgagttgaa actggaatcc gttgtcatcg tctctagaca tggtgttaga 60
gcaccaacca aggccaccca acttatgcaa gatgtcaccc cagacgcttg gccaacctgg 120
ccagtcaagc tgggttggtt gacacctaga ggtggtgagc tcattgctta cttgggtcac 180
taccaaagac agcgtcttgt tgccgacgga ttgttggcca agaagggttg tccacaatct 240
ggtcaagtag ctattattgc tgacgtcgac gaaagaaccc gtaagacagg tgaagccttc 300
gccgccggtc ttgctcctga ctgtgccatt accgttcaca cccaagctga cacttcttct 360
ccagatccat tgttcaaccc ttgtaagact ggtgtttgcc aattggacaa cgctaacgtt 420
actgacgcta tcttgtccag agctggagga tccattgctg acttcaccgg tcacagacag 480
actgccttca gagagttgga aagagttctt aacttcccac aatcaaactt gtgcttgaag 540
cgtgagaagc aagacgaatc ctgttccttg actcaagcat taccatctga gttgaaggtc 600
tccgcctgta acgtctcttt gaccggtgct gtcagcttgg cttccatgtt gactgaaatc 660
tttcttctgc aacaagctca aggtatgcct gagccaggtt ggggtagaat caccgactct 720
caccaatgga acaccttgtt gtccttgcac aacgctcaat tctacttgct gcagagaact 780
ccagaggttg ctagatccag agccacccca ttgttggact tgatcaagac tgctttgact 840
cctcacccac ctcaaaagca agcctacggt gttaccttgc ccacttctgt cttgttcatt 900
gccggtcacg atactaactt ggcaaatctc ggcggtgctt tggagttgaa ctggactctt 960
cctggtcaac ctgataacac tccaccaggt ggtgagctcg ttttcgaaag atggcgtaga 1020
ctatctgata actctcaatg gattcaggtt tcgttggtct tccaaacttt gcagcagatg 1080
agagacaaga ctccactgtc tttgaacacg cctccaggag aagtcaaatt gaccttggct 1140
ggatgtgaag agagaaatgc tcagggtatg tgttccttgg ctggtttcac tcaaatcgtt 1200
aacgaagcta gaatcccagc ttgttccttg tag 1233
<210> 47
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPA-G
<400> 47
cagagtgagc ctgagttgaa actggaatcc gttgtcatcg tctctagaca tggtgttaga 60
gcaccaacca aggccaccca acttatgcaa gatgtcaccc cagacgcttg gccaacctgg 120
ccagtcaagc tgggttggtt gacacctaga ggtggtgagc tcattgctta cttgggtcac 180
taccaaagac agcgtcttgt tgccgacgga ttgttggcca agaagggttg tccacaatct 240
ggtcaagtag ctattattgc tgacgtcgac gaaagaaccc gtaagacagg tgaagccttc 300
gccgccggtc ttgctcctga ctgtgccatt accgttcaca cccaagctga cacttcttct 360
ccagatccat tgttcaaccc tttgaagact ggtgtttgcc aattggacaa cgctaactgt 420
actgacgcta tcttgtccag agctggagga tccattgctg acttcaccgg tcacagacag 480
actgccttca gagagttgga aagagttctt aacttcccac aatcaaactt gtgcttgaag 540
cgtgagaagc aagacgaatc ctgttccttg actcaagcat taccatctga gttgaaggtc 600
tccgccgaca acgtctcttt gaccggtgct gtcagcttgg cttccatgtt gactgaaatc 660
tttcttctgc aacaagctca aggtatgcct gagccaggtt ggggtagaat caccgactct 720
caccaatgga acaccttgtt gtccttgcac aacgctcaat tctacttgct gcagagaact 780
ccatgtgttg ctagatccag agccacccca ttgttggact tgatcaagac tgctttgact 840
cctcacccac ctcaaaagca agcctacggt gttaccttgc ccacttctgt cttgttcatt 900
gccggtcacg atactaactt ggcaaatctc ggcggtgctt tggagttgaa ctggactctt 960
cctggtcaac ctgataacac tccaccaggt ggtgagctcg ttttcgaaag atggcgtaga 1020
ctatctgata actctcaatg gattcaggtt tcgttggtct tccaaacttt gcagcagatg 1080
agagacaaga ctccactgtc tttgaacacg cctccaggag aagtcaaatt gaccttggct 1140
ggatgtgaag agagaaatgc tcagggtatg tgttccttgg ctggtttcac tcaaatcgtt 1200
aacgaagcta gaatcccagc ttgttccttg tag 1233
<210> 48
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPA-H
<400> 48
cagagtgagc ctgagttgaa actggaatcc gttgtcatcg tctctagaca tggtgttaga 60
gcaccaacca aggccaccca acttatgcaa gatgtcaccc cagacgcttg gccaacctgg 120
ccagtcaagc tgggttggtt gacacctaga ggtggtgagc tcattgctta cttgggtcac 180
taccaaagac agcgtcttgt tgccgacgga ttgttggcca agaagggttg tccacaatct 240
ggtcaagtag ctattattgc tgacgtcgac gaaagaaccc gtaagacagg tgaagccttc 300
gccgccggtc ttgctcctga ctgtgccatt accgttcaca cccaagctga cacttcttct 360
ccagatccat tgttcaaccc tttgaagact ggtgtttgcc aattggacaa cgctaacgtt 420
actgacgcta tcttgtccag agctggagga tccattgctg acttctgtgg tcacagacag 480
actgccttca gagagttgga aagagttctt aacttcccac aatcaaactt gtgcttgaag 540
cgtgagaagc aagacgaatc ctgttccttg tgtcaagcat taccatctga gttgaaggtc 600
tccgccgaca acgtctcttt gaccggtgct gtcagcttgg cttccatgtt gactgaaatc 660
tttcttctgc aacaagctca aggtatgcct gagccaggtt ggggtagaat caccgactct 720
caccaatgga acaccttgtt gtccttgcac aacgctcaat tctacttgct gcagagaact 780
ccagaggttg ctagatccag agccacccca ttgttggact tgatcaagac tgctttgact 840
cctcacccac ctcaaaagca agcctacggt gttaccttgc ccacttctgt cttgttcatt 900
gccggtcacg atactaactt ggcaaatctc ggcggtgctt tggagttgaa ctggactctt 960
cctggtcaac ctgataacac tccaccaggt ggtgagctcg ttttcgaaag atggcgtaga 1020
ctatctgata actctcaatg gattcaggtt tcgttggtct tccaaacttt gcagcagatg 1080
agagacaaga ctccactgtc tttgaacacg cctccaggag aagtcaaatt gaccttggct 1140
ggatgtgaag agagaaatgc tcagggtatg tgttccttgg ctggtttcac tcaaatcgtt 1200
aacgaagcta gaatcccagc ttgttccttg tag 1233
<210> 49
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPA-I
<400> 49
cagagtgagc ctgagttgaa actggaatcc gttgtcatcg tctctagaca tggtgttaga 60
gcaccaacca aggccaccca acttatgcaa gatgtcaccc cagacgcttg gccaacctgg 120
ccagtcaagc tgggttggtt gacacctaga ggtggtgagc tcattgctta cttgggtcac 180
taccaaagac agcgtcttgt tgccgacgga ttgttggcca agaagggttg tccacaatct 240
ggtcaagtag ctattattgc tgacgtcgac gaaagaaccc gtaagacagg tgaagccttc 300
gccgccggtc ttgctcctga ctgtgccatt accgttcaca cccaagctga cacttcttct 360
ccagatccat tgttcaaccc tttgaagact ggtgtttgcc aattggacaa cgctaacgtt 420
actgacgcta tcttgtccag agctggagga tccattgctg acttcaccgg tcacagacag 480
actgccttca gatgtttgga aagagttctt aacttcccac aatcaaactt gtgcttgaag 540
cgtgagaagc aagacgaatc ctgttccttg actcaagcat taccatctga gttgaaggtc 600
tccgccgaca acgtctcttt gaccggtgct gtcagcttgg cttccatgtt gactgaaatc 660
tttcttctgc aacaagctca aggtatgcct gagccaggtt ggggtagaat caccgactct 720
caccaatgga actgtttgtt gtccttgcac aacgctcaat tctacttgct gcagagaact 780
ccagaggttg ctagatccag agccacccca ttgttggact tgatcaagac tgctttgact 840
cctcacccac ctcaaaagca agcctacggt gttaccttgc ccacttctgt cttgttcatt 900
gccggtcacg atactaactt ggcaaatctc ggcggtgctt tggagttgaa ctggactctt 960
cctggtcaac ctgataacac tccaccaggt ggtgagctcg ttttcgaaag atggcgtaga 1020
ctatctgata actctcaatg gattcaggtt tcgttggtct tccaaacttt gcagcagatg 1080
agagacaaga ctccactgtc tttgaacacg cctccaggag aagtcaaatt gaccttggct 1140
ggatgtgaag agagaaatgc tcagggtatg tgttccttgg ctggtttcac tcaaatcgtt 1200
aacgaagcta gaatcccagc ttgttccttg tag 1233
<210> 50
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPA-J
<400> 50
cagagtgagc ctgagttgaa actggaatcc gttgtcatcg tctctagaca tggtgttaga 60
gcaccaacca aggccaccca acttatgcaa gatgtcaccc cagacgcttg gccaacctgg 120
ccagtcaagc tgggttggtt gacacctaga ggtggtgagc tcattgctta cttgggtcac 180
taccaaagac agcgtcttgt tgccgacgga ttgttggcca agaagggttg tccacaatct 240
ggtcaagtag ctattattgc tgacgtcgac gaaagaaccc gtaagacagg tgaagccttc 300
gccgccggtc ttgctcctga ctgtgccatt accgttcaca cccaagctga cacttcttct 360
ccagatccat tgttcaaccc tttgaagact ggtgtttgcc aattggacaa cgctaacgtt 420
actgacgcta tcttgtccag agctggagga tccattgctg acttcaccgg tcacagacag 480
actgccttca gagagttgga aagagttctt aacttcccac aatcaaactt gtgcttgaag 540
cgtgagaagc aagacgaatc ctgttccttg tgtcaagcat taccatctga gttgaaggtc 600
tccgccgaca acgtctcttt gaccggttgt gtcagcttgg cttccatgtt gactgaaatc 660
tttcttctgc aacaagctca aggtatgcct gagccaggtt ggggtagaat caccgactct 720
caccaatgga acaccttgtt gtccttgcac aacgctcaat tctacttgct gcagagaact 780
ccagaggttg ctagatccag agccacccca ttgttggact tgatcaagac tgctttgact 840
cctcacccac ctcaaaagca agcctacggt gttaccttgc ccacttctgt cttgttcatt 900
gccggtcacg atactaactt ggcaaatctc ggcggtgctt tggagttgaa ctggactctt 960
cctggtcaac ctgataacac tccaccaggt ggtgagctcg ttttcgaaag atggcgtaga 1020
ctatctgata actctcaatg gattcaggtt tcgttggtct tccaaacttt gcagcagatg 1080
agagacaaga ctccactgtc tttgaacacg cctccaggag aagtcaaatt gaccttggct 1140
ggatgtgaag agagaaatgc tcagggtatg tgttccttgg ctggtttcac tcaaatcgtt 1200
aacgaagcta gaatcccagc ttgttccttg tag 1233
<210> 51
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPA-K
<400> 51
cagagtgagc ctgagttgaa actggaatcc gttgtcatcg tctctagaca tggtgttaga 60
gcaccaacca aggccaccca acttatgcaa gatgtcaccc cagacgcttg gccaacctgg 120
ccagtcaagc tgggttggtt gacacctaga ggtggtgagc tcattgctta cttgggtcac 180
taccaaagac agcgtcttgt tgccgacgga ttgttggcca agaagggttg tccacaatct 240
ggtcaagtag ctattattgc tgacgtcgac gaaagaaccc gtaagacagg tgaagccttc 300
gccgccggtc ttgctcctga ctgtgccatt accgttcaca cccaagctga cacttcttct 360
ccagatccat tgttcaaccc tttgaagact ggtgtttgcc aattggacaa cgctaacgtt 420
actgacgcta tcttgtccag agctggagga tccattgctg acttcaccgg tcacagacag 480
actgccttca gagagttgga aagagttctt aacttcccac aatcaaactt gtgcttgaag 540
cgtgagaagc aagacgaatc ctgttccttg actcaagcat taccatgtga gttgaaggtc 600
tccgccgaca acgtctcttt gaccggtgct tgtagcttgg cttccatgtt gactgaaatc 660
tttcttctgc aacaagctca aggtatgcct gagccaggtt ggggtagaat caccgactct 720
caccaatgga acaccttgtt gtccttgcac aacgctcaat tctacttgct gcagagaact 780
ccagaggttg ctagatccag agccacccca ttgttggact tgatcaagac tgctttgact 840
cctcacccac ctcaaaagca agcctacggt gttaccttgc ccacttctgt cttgttcatt 900
gccggtcacg atactaactt ggcaaatctc ggcggtgctt tggagttgaa ctggactctt 960
cctggtcaac ctgataacac tccaccaggt ggtgagctcg ttttcgaaag atggcgtaga 1020
ctatctgata actctcaatg gattcaggtt tcgttggtct tccaaacttt gcagcagatg 1080
agagacaaga ctccactgtc tttgaacacg cctccaggag aagtcaaatt gaccttggct 1140
ggatgtgaag agagaaatgc tcagggtatg tgttccttgg ctggtttcac tcaaatcgtt 1200
aacgaagcta gaatcccagc ttgttccttg tag 1233
<210> 52
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPA-L
<400> 52
cagagtgagc ctgagttgaa actggaatcc gttgtcatcg tctctagaca tggtgttaga 60
gcaccaacca aggccaccca acttatgcaa gatgtcaccc cagacgcttg gccaacctgg 120
ccagtcaagc tgggttggtt gacacctaga ggtggtgagc tcattgctta cttgggtcac 180
taccaaagac agcgtcttgt tgccgacgga ttgttggcca agaagggttg tccacaatct 240
ggtcaagtag ctattattgc tgacgtcgac gaaagaaccc gtaagacagg tgaagccttc 300
gccgccggtc ttgctcctga ctgtgccatt accgttcaca cccaagctga cacttcttct 360
ccagatccat tgttcaaccc tttgaagact ggtgtttgcc aattggacaa cgctaacgtt 420
actgacgcta tcttgtccag agctggagga tccattgctg acttcaccgg tcacagacag 480
actgccttca gagagttgga aagagttctt aacttcccac aatcaaactt gtgcttgaag 540
cgtgagaagc aagacgaatc ctgttccttg actcaagcat taccatctga gttgaaggtc 600
tccgccgaca acgtctcttt gaccggtgct gtcagcttgg cttccatgtt gactgaaatc 660
tttcttctgc aacaagctca aggtatgcct gagccaggtt ggggtagaat caccgactct 720
caccaatgga acaccttgtt gtccttgcac aacgctcaat tctacttgct gcagagaact 780
ccagaggttt gtagatccag agccacccca ttgttggact tgatcaagac tgctttgact 840
cctcacccac ctcaaaagca agcctacggt gttaccttgc ccacttctgt cttgttcatt 900
gccggtcacg atactaactt ggcaaatctc ggctgtgctt tggagttgaa ctggactctt 960
cctggtcaac ctgataacac tccaccaggt ggtgagctcg ttttcgaaag atggcgtaga 1020
ctatctgata actctcaatg gattcaggtt tcgttggtct tccaaacttt gcagcagatg 1080
agagacaaga ctccactgtc tttgaacacg cctccaggag aagtcaaatt gaccttggct 1140
ggatgtgaag agagaaatgc tcagggtatg tgttccttgg ctggtttcac tcaaatcgtt 1200
aacgaagcta gaatcccagc ttgttccttg tag 1233
<210> 53
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPA-M
<400> 53
cagagtgagc ctgagttgaa actggaatcc gttgtcatcg tctctagaca tggtgttaga 60
gcaccaacca aggccaccca acttatgcaa gatgtcaccc cagacgcttg gccaacctgg 120
ccagtcaagc tgggttggtt gacacctaga ggtggtgagc tcattgctta cttgggtcac 180
taccaaagac agcgtcttgt tgccgacgga ttgttggcca agaagggttg tccacaatct 240
ggtcaagtag ctattattgc tgacgtcgac gaaagaaccc gtaagacagg tgaagccttc 300
gccgccggtc ttgctcctga ctgtgccatt accgttcaca cccaagctga cacttcttct 360
ccagatccat tgttcaaccc tttgaagact ggtgtttgcc aattggacaa cgctaacgtt 420
actgacgcta tcttgtccag agctggagga tccattgctg acttcaccgg tcacagacag 480
actgccttca gagagttgga aagagttctt aacttcccac aatcaaactt gtgcttgaag 540
cgtgagaagc aagacgaatc ctgttccttg actcaagcat taccatctga gttgaaggtc 600
tccgccgaca acgtctcttt gaccggtgct gtcagcttgg cttccatgtt gactgaaatc 660
tttcttctgc aacaagctca aggtatgcct gagccaggtt ggggtagaat caccgactct 720
caccaatgga acaccttgtt gtccttgcac aacgctcaat tctacttgct gcagagaact 780
ccagaggttg ctagatccag agccacccca ttgttggact tgatcaagac tgctttgact 840
cctcacccac ctcaaaagca agcctacggt gttaccttgc ccacttctgt cttgttcatt 900
gccggtcacg atactaactt ggcaaatctc ggcggtgctt tgtgtttgaa ctggactctt 960
cctggtcaac ctgataacac tccaccaggt ggtgagctcg ttttcgaaag atggcgtaga 1020
ctatctgata actctcaatg gattcaggtt tcgttggtct tccaaacttt gcagcagatg 1080
agagacaaga ctccactgtc tttgaacacg cctccaggag aagtcaaatt gaccttgtgt 1140
ggatgtgaag agagaaatgc tcagggtatg tgttccttgg ctggtttcac tcaaatcgtt 1200
aacgaagcta gaatcccagc ttgttccttg tag 1233
<210> 54
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPA-N
<400> 54
cagagtgagc ctgagttgaa actggaatcc gttgtcatcg tctctagaca tggtgttaga 60
gcaccaacca aggccaccca acttatgcaa gatgtcaccc cagacgcttg gccaacctgg 120
ccagtcaagc tgggttggtt gacacctaga ggtggtgagc tcattgctta cttgggtcac 180
taccaaagac agcgtcttgt tgccgacgga ttgttggcca agaagggttg tccacaatct 240
ggtcaagtag ctattattgc tgacgtcgac gaaagaaccc gtaagacagg tgaagccttc 300
gccgccggtc ttgctcctga ctgtgccatt accgttcaca cccaagctga cacttcttct 360
ccagatccat tgttcaaccc tttgaagact ggtgtttgcc aattggacaa cgctaacgtt 420
actgacgcta tcttgtccag agctggagga tccattgctg acttcaccgg tcacagacag 480
actgccttca gagagttgga aagagttctt aacttcccac aatcaaactt gtgcttgaag 540
cgtgagaagc aagacgaatc ctgttccttg actcaagcat taccatctga gttgaaggtc 600
tccgccgaca acgtctcttt gaccggtgct gtcagcttgg cttccatgtt gactgaaatc 660
tttcttctgc aacaagctca aggtatgcct gagccaggtt ggggtagaat caccgactct 720
caccaatgga acaccttgtt gtccttgcac aacgctcaat tctacttgct gcagagaact 780
ccagaggttg ctagatccag agccacccca ttgttggact tgatcaagac tgctttgact 840
cctcacccac ctcaaaagca agcctacggt gttaccttgc ccacttctgt cttgttcatt 900
gccggtcacg atactaactt ggcaaatctc ggcggtgctt tggagttgaa ctggactctt 960
ccttgtcaac ctgataacac tccaccaggt ggtgagctcg ttttcgaaag atggcgtaga 1020
ctatctgata actctcaatg gattcaggtt tcgttggtct tccaatgttt gcagcagatg 1080
agagacaaga ctccactgtc tttgaacacg cctccaggag aagtcaaatt gaccttggct 1140
ggatgtgaag agagaaatgc tcagggtatg tgttccttgg ctggtttcac tcaaatcgtt 1200
aacgaagcta gaatcccagc ttgttccttg tag 1233
<210> 55
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPA-O
<400> 55
cagagtgagc ctgagttgaa actggaatcc gttgtcatcg tctctagaca tggtgttaga 60
gcaccaacca aggccaccca acttatgcaa gatgtcaccc cagacgcttg gccaacctgg 120
ccagtcaagc tgggttggtt gacacctaga ggtggtgagc tcattgctta cttgggtcac 180
taccaaagac agcgtcttgt tgccgacgga ttgttggcca agaagggttg tccacaatct 240
ggtcaagtag ctattattgc tgacgtcgac gaaagaaccc gtaagacagg tgaagccttc 300
gccgccggtc ttgctcctga ctgtgccatt accgttcaca cccaagctga cacttcttct 360
ccagatccat tgttcaaccc tttgaagact ggtgtttgcc aattggacaa cgctaacgtt 420
actgacgcta tcttgtccag agctggagga tccattgctg acttcaccgg tcacagacag 480
actgccttca gagagttgga aagagttctt aacttcccac aatcaaactt gtgcttgaag 540
cgtgagaagc aagacgaatc ctgttccttg actcaagcat taccatctga gttgaaggtc 600
tccgccgaca acgtctcttt gaccggtgct gtcagcttgg cttccatgtt gactgaaatc 660
tttcttctgc aacaagctca aggtatgcct gagccaggtt ggggtagaat caccgactct 720
caccaatgga acaccttgtt gtccttgcac aacgctcaat tctacttgct gcagagaact 780
ccagaggttg ctagatccag agccacccca ttgttggact tgatcaagac tgctttgact 840
cctcacccac ctcaaaagca agcctacggt gttaccttgc ccacttctgt cttgttcatt 900
gccggtcacg atactaactt ggcaaatctc ggcggtgctt tggagttgaa ctggactctt 960
cctggtcaac ctgataacac tccaccaggt ggtgagctcg ttttcgaaag atggcgtaga 1020
ctatctgata actcttgttg gattcaggtt tcgttggtct tccaaacttt gcagcagatg 1080
agagacaaga ctccactgtc tttgaacacg cctccaggag aagtcaaatt gaccttggct 1140
ggatgtgaag agagaaatgc tcagggtatg tgttcctgtg ctggtttcac tcaaatcgtt 1200
aacgaagcta gaatcccagc ttgttccttg tag 1233
<210> 56
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPA-P
<400> 56
cagagtgagc ctgagttgaa actggaatcc gttgtcatcg tctctagaca tggtgttaga 60
gcaccaacca aggccaccca acttatgcaa gatgtcaccc cagacgcttg gccaacctgg 120
ccagtcaagc tgggttggtt gacacctaga ggtggtgagc tcattgctta cttgggtcac 180
taccaaagac agcgtcttgt tgccgacgga ttgttggcca agaagggttg tccacaatct 240
ggtcaagtag ctattattgc tgacgtcgac gaaagaaccc gtaagacagg tgaagccttc 300
gccgccggtc ttgctcctga ctgtgccatt accgttcaca cccaagctga cacttcttct 360
ccagatccat tgttcaaccc tttgaagact ggtgtttgcc aattggacaa cgctaacgtt 420
actgacgcta tcttgtccag agctggagga tccattgctg acttcaccgg tcacagacag 480
actgccttca gagagttgga aagagttctt aacttcccac aatcaaactt gtgcttgaag 540
cgtgagaagc aagacgaatc ctgttccttg actcaagcat taccatctga gttgaaggtc 600
tccgccgaca acgtctcttt gaccggtgct gtcagcttgg cttccatgtt gactgaaatc 660
tttcttctgc aacaagctca aggtatgcct gagccaggtt ggggtagaat caccgactct 720
caccaatgga acaccttgtt gtccttgcac aacgctcaat tctacttgct gcagagaact 780
ccagaggttg ctagatccag agccacccca ttgttggact tgatcaagac tgctttgact 840
cctcacccac ctcaaaagca agcctacggt gttaccttgc ccacttctgt cttgttcatt 900
gccggtcacg atactaactt ggcaaatctc ggcggtgctt tggagttgaa ctggactctt 960
cctggtcaac ctgataacac tccaccaggt ggtgagctcg ttttcgaaag atggcgtaga 1020
ctatctgata actctcaatg gatttgtgtt tcgttggtct tccaaacttt gcagcagatg 1080
agagacaaga ctccactgtc tttgaacacg cctccaggag aagtcaaatt gaccttggct 1140
ggatgtgaag agagaaatgc tcagggttgt tgttccttgg ctggtttcac tcaaatcgtt 1200
aacgaagcta gaatcccagc ttgttccttg tag 1233
<210> 57
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPA-M1-D
<400> 57
cagagtgagc ctgagttgaa actggaatcc gttgtcatcg tctctagaca tggtgttaga 60
gcaccaacca agttcaccca acttatgcaa gatgtcaccc cagacgcttg gccaacctgg 120
ccagtcaagc tgggtgaatt gacacctaga ggtggtgagc tcattgctta cttgggtcac 180
tgttggagac agcgtcttgt tgccgacgaa ttgttgccta agtgtggttg tccacaatct 240
ggtcaagtag ctattattgc tgacgtcgac gaaagaaccc gtaagacagg tgaagccttc 300
gccgccggtc ttgctcctga ctgtgccatt accgttcacc atcaagctga cacttcttct 360
ccagatccat tgttcaaccc tttgaagact ggtgtttgcc aattggacgt tgctaacgtt 420
actagagcta tcttggaaag agctggagga tctattgctg acttcaccgg tcactaccag 480
actgccttca gagagttgga aagagttctt aacttcccac aatccaactt gtgccttaag 540
cgtgagaagc aagacgaatc ctgttccttg actcaagcat taccatctga gttgaaggtc 600
tccgccgaca acgtctcttt gaccggtgct gtcagcttgg cttccatgtt gactgaaatc 660
tttcttctgc aacaagctca aggtatgcct gagccaggtt ggggtagaat caccgactct 720
caccaatgga acaccttgtt gtccttgcac aacgctcaat tcgatttgct gcagagaact 780
ccagaggttg ctagatccag agccacccca ttgttggact tgatcaagac tgctttgact 840
cctcacccac ctcaaaagca agcctacggt gttaccttgc ccacttctgt cttgttcatt 900
gccggtcacg atactaactt ggcaaatctc ggcggtgctt tggagttgaa ctggactctt 960
cctggtcaac ctgataacac tccaccaggt ggtgagctcg ttttcgaaag atggcgtaga 1020
ctatctgata actctcaatg gattcaggtt tcgttggtct tccaaacttt gcagcagatg 1080
agagacaaga ctccatgttc tttgaacacg cctccaggag aagtcaaatt gaccttggct 1140
ggatgtgaag agagaaatgc tcagggtatg tgttccttgg ctggtttcac tcaaatcgtt 1200
aacgaagcta gaatcccagc ttgttccttg tag 1233
<210> 58
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPA-M1-O
<400> 58
cagagtgagc ctgagttgaa actggaatcc gttgtcatcg tctctagaca tggtgttaga 60
gcaccaacca agttcaccca acttatgcaa gatgtcaccc cagacgcttg gccaacctgg 120
ccagtcaagc tgggtgaatt gacacctaga ggtggtgagc tcattgctta cttgggtcac 180
tactggagac agcgtcttgt tgccgacgaa ttgttgccta agtgtggttg tccacaatct 240
ggtcaagtag ctattattgc tgacgtcgac gaaagaaccc gtaagacagg tgaagccttc 300
gccgccggtc ttgctcctga ctgtgccatt accgttcacc atcaagctga cacttcttct 360
ccagatccat tgttcaaccc tttgaagact ggtgtttgcc aattggacgt tgctaacgtt 420
actagagcta tcttggaaag agctggagga tctattgctg acttcaccgg tcactaccag 480
actgccttca gagagttgga aagagttctt aacttcccac aatccaactt gtgccttaag 540
cgtgagaagc aagacgaatc ctgttccttg actcaagcat taccatctga gttgaaggtc 600
tccgccgaca acgtctcttt gaccggtgct gtcagcttgg cttccatgtt gactgaaatc 660
tttcttctgc aacaagctca aggtatgcct gagccaggtt ggggtagaat caccgactct 720
caccaatgga acaccttgtt gtccttgcac aacgctcaat tcgatttgct gcagagaact 780
ccagaggttg ctagatccag agccacccca ttgttggact tgatcaagac tgctttgact 840
cctcacccac ctcaaaagca agcctacggt gttaccttgc ccacttctgt cttgttcatt 900
gccggtcacg atactaactt ggcaaatctc ggcggtgctt tggagttgaa ctggactctt 960
cctggtcaac ctgataacac tccaccaggt ggtgagctcg ttttcgaaag atggcgtaga 1020
ctatctgata actcttgttg gattcaggtt tcgttggtct tccaaacttt gcagcagatg 1080
agagacaaga ctccactgtc tttgaacacg cctccaggag aagtcaaatt gaccttggct 1140
ggatgtgaag agagaaatgc tcagggtatg tgttcctgtg ctggtttcac tcaaatcgtt 1200
aacgaagcta gaatcccagc ttgttccttg tag 1233
<210> 59
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPA-M1-BO
<400> 59
cagagtgagc ctgagttgaa actggaatcc gttgtcatcg tctctagaca tggtgttaga 60
gcaccaacca agttcaccca acttatgcaa gatgtcaccc cagacgcttg gccaacctgg 120
ccagtcaagc tgggtgaatt gacacctaga ggtggtgagc tcatttgtta cttgggtcac 180
tactggagac agcgtcttgt tgccgacgaa ttgttgccta agtgtggttg tccacaatct 240
ggtcaagtag ctattattgc tgacgtcgac gaaagaaccc gtaagacagg tgaagccttc 300
gccgcctgtc ttgctcctga ctgtgccatt accgttcacc atcaagctga cacttcttct 360
ccagatccat tgttcaaccc tttgaagact ggtgtttgcc aattggacgt tgctaacgtt 420
actagagcta tcttggaaag agctggagga tctattgctg acttcaccgg tcactaccag 480
actgccttca gagagttgga aagagttctt aacttcccac aatccaactt gtgccttaag 540
cgtgagaagc aagacgaatc ctgttccttg actcaagcat taccatctga gttgaaggtc 600
tccgccgaca acgtctcttt gaccggtgct gtcagcttgg cttccatgtt gactgaaatc 660
tttcttctgc aacaagctca aggtatgcct gagccaggtt ggggtagaat caccgactct 720
caccaatgga acaccttgtt gtccttgcac aacgctcaat tcgatttgct gcagagaact 780
ccagaggttg ctagatccag agccacccca ttgttggact tgatcaagac tgctttgact 840
cctcacccac ctcaaaagca agcctacggt gttaccttgc ccacttctgt cttgttcatt 900
gccggtcacg atactaactt ggcaaatctc ggcggtgctt tggagttgaa ctggactctt 960
cctggtcaac ctgataacac tccaccaggt ggtgagctcg ttttcgaaag atggcgtaga 1020
ctatctgata actcttgttg gattcaggtt tcgttggtct tccaaacttt gcagcagatg 1080
agagacaaga ctccactgtc tttgaacacg cctccaggag aagtcaaatt gaccttggct 1140
ggatgtgaag agagaaatgc tcagggtatg tgttcctgtg ctggtttcac tcaaatcgtt 1200
aacgaagcta gaatcccagc ttgttccttg tag 1233
<210> 60
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPA-M1-CO
<400> 60
cagagtgagc ctgagttgaa actggaatcc gttgtcatcg tctctagaca tggtgttaga 60
gcaccaacca agttcaccca acttatgcaa gatgtcaccc cagacgcttg gccaacctgg 120
ccagtcaagc tgggtgaatt gacacctaga ggtggtgagc tcattgcttg tttgggtcac 180
tactggagac agcgtcttgt tgccgacgaa ttgttgccta agtgtggttg tccacaatct 240
ggtcaagtag ctattattgc tgacgtcgac gaaagaaccc gtaagacagg tgaagccttc 300
gccgccggtc ttgctcctga ctgtgccatt accgttcacc atcaagctga cacttcttct 360
ccagatccat tgttcaaccc tttgaagact ggtgtttgcc aattggacgt tgctaacgtt 420
actagagcta tcttggaaag agctggagga tctattgctg acttcaccgg tcactaccag 480
actgccttca gagagttgga aagagttctt aacttcccac aatccaactt gtgccttaag 540
cgtgagaagc aagacgaatc ctgttccttg actcaagcat taccatctga gttgaaggtc 600
tccgccgaca acgtctcttt gaccggtgct gtcagcttgg cttccatgtt gactgaaatc 660
tttcttctgc aacaagctca aggtatgcct gagccaggtt ggggtagaat caccgactct 720
caccaatgga acaccttgtt gtccttgcac aacgctcaat tcgatttgct gcagagaact 780
ccagaggttg ctagatccag agccacccca ttgttggact tgatcaagac tgctttgact 840
cctcacccac ctcaaaagca agcctacggt gttaccttgc ccacttctgt cttgttcatt 900
gccggtcacg atactaactt ggcaaatctc ggcggtgctt tggagttgaa ctggactctt 960
cctggtcaac ctgataacac tccaccaggt ggtgagctcg ttttcgaaag atggcgtaga 1020
ctatctgata actcttgttg gattcaggtt tcgttggtct tccaaacttt gcagcagatg 1080
agagacaaga ctccatgttc tttgaacacg cctccaggag aagtcaaatt gaccttggct 1140
ggatgtgaag agagaaatgc tcagggtatg tgttcctgtg ctggtttcac tcaaatcgtt 1200
aacgaagcta gaatcccagc ttgttccttg tag 1233
<210> 61
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPA-M1-DO
<400> 61
cagagtgagc ctgagttgaa actggaatcc gttgtcatcg tctctagaca tggtgttaga 60
gcaccaacca agttcaccca acttatgcaa gatgtcaccc cagacgcttg gccaacctgg 120
ccagtcaagc tgggtgaatt gacacctaga ggtggtgagc tcattgctta cttgggtcac 180
tgttggagac agcgtcttgt tgccgacgaa ttgttgccta agtgtggttg tccacaatct 240
ggtcaagtag ctattattgc tgacgtcgac gaaagaaccc gtaagacagg tgaagccttc 300
gccgccggtc ttgctcctga ctgtgccatt accgttcacc atcaagctga cacttcttct 360
ccagatccat tgttcaaccc tttgaagact ggtgtttgcc aattggacgt tgctaacgtt 420
actagagcta tcttggaaag agctggagga tctattgctg acttcaccgg tcactaccag 480
actgccttca gagagttgga aagagttctt aacttcccac aatccaactt gtgccttaag 540
cgtgagaagc aagacgaatc ctgttccttg actcaagcat taccatctga gttgaaggtc 600
tccgccgaca acgtctcttt gaccggtgct gtcagcttgg cttccatgtt gactgaaatc 660
tttcttctgc aacaagctca aggtatgcct gagccaggtt ggggtagaat caccgactct 720
caccaatgga acaccttgtt gtccttgcac aacgctcaat tcgatttgct gcagagaact 780
ccagaggttg ctagatccag agccacccca ttgttggact tgatcaagac tgctttgact 840
cctcacccac ctcaaaagca agcctacggt gttaccttgc ccacttctgt cttgttcatt 900
gccggtcacg atactaactt ggcaaatctc ggcggtgctt tggagttgaa ctggactctt 960
cctggtcaac ctgataacac tccaccaggt ggtgagctcg ttttcgaaag atggcgtaga 1020
ctatctgata actcttgttg gattcaggtt tcgttggtct tccaaacttt gcagcagatg 1080
agagacaaga ctccatgttc tttgaacacg cctccaggag aagtcaaatt gaccttggct 1140
ggatgtgaag agagaaatgc tcagggtatg tgttcctgtg ctggtttcac tcaaatcgtt 1200
aacgaagcta gaatcccagc ttgttccttg tag 1233
<210> 62
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPA-M1-MO
<400> 62
cagagtgagc ctgagttgaa actggaatcc gttgtcatcg tctctagaca tggtgttaga 60
gcaccaacca agttcaccca acttatgcaa gatgtcaccc cagacgcttg gccaacctgg 120
ccagtcaagc tgggtgaatt gacacctaga ggtggtgagc tcattgctta cttgggtcac 180
tactggagac agcgtcttgt tgccgacgaa ttgttgccta agtgtggttg tccacaatct 240
ggtcaagtag ctattattgc tgacgtcgac gaaagaaccc gtaagacagg tgaagccttc 300
gccgccggtc ttgctcctga ctgtgccatt accgttcacc atcaagctga cacttcttct 360
ccagatccat tgttcaaccc tttgaagact ggtgtttgcc aattggacgt tgctaacgtt 420
actagagcta tcttggaaag agctggagga tctattgctg acttcaccgg tcactaccag 480
actgccttca gagagttgga aagagttctt aacttcccac aatccaactt gtgccttaag 540
cgtgagaagc aagacgaatc ctgttccttg actcaagcat taccatctga gttgaaggtc 600
tccgccgaca acgtctcttt gaccggtgct gtcagcttgg cttccatgtt gactgaaatc 660
tttcttctgc aacaagctca aggtatgcct gagccaggtt ggggtagaat caccgactct 720
caccaatgga acaccttgtt gtccttgcac aacgctcaat tcgatttgct gcagagaact 780
ccagaggttg ctagatccag agccacccca ttgttggact tgatcaagac tgctttgact 840
cctcacccac ctcaaaagca agcctacggt gttaccttgc ccacttctgt cttgttcatt 900
gccggtcacg atactaactt ggcaaatctc ggcggtgctt tgtgtttgaa ctggactctt 960
cctggtcaac ctgataacac tccaccaggt ggtgagctcg ttttcgaaag atggcgtaga 1020
ctatctgata actcttgttg gattcaggtt tcgttggtct tccaaacttt gcagcagatg 1080
agagacaaga ctccactgtc tttgaacacg cctccaggag aagtcaaatt gaccttgtgt 1140
ggatgtgaag agagaaatgc tcagggtatg tgttcctgtg ctggtttcac tcaaatcgtt 1200
aacgaagcta gaatcccagc ttgttccttg tag 1233
<210> 63
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPA-M1-BDO
<400> 63
cagagtgagc ctgagttgaa actggaatcc gttgtcatcg tctctagaca tggtgttaga 60
gcaccaacca agttcaccca acttatgcaa gatgtcaccc cagacgcttg gccaacctgg 120
ccagtcaagc tgggtgaatt gacacctaga ggtggtgagc tcatttgtta cttgggtcac 180
tgttggagac agcgtcttgt tgccgacgaa ttgttgccta agtgtggttg tccacaatct 240
ggtcaagtag ctattattgc tgacgtcgac gaaagaaccc gtaagacagg tgaagccttc 300
gccgcctgtc ttgctcctga ctgtgccatt accgttcacc atcaagctga cacttcttct 360
ccagatccat tgttcaaccc tttgaagact ggtgtttgcc aattggacgt tgctaacgtt 420
actagagcta tcttggaaag agctggagga tctattgctg acttcaccgg tcactaccag 480
actgccttca gagagttgga aagagttctt aacttcccac aatccaactt gtgccttaag 540
cgtgagaagc aagacgaatc ctgttccttg actcaagcat taccatctga gttgaaggtc 600
tccgccgaca acgtctcttt gaccggtgct gtcagcttgg cttccatgtt gactgaaatc 660
tttcttctgc aacaagctca aggtatgcct gagccaggtt ggggtagaat caccgactct 720
caccaatgga acaccttgtt gtccttgcac aacgctcaat tcgatttgct gcagagaact 780
ccagaggttg ctagatccag agccacccca ttgttggact tgatcaagac tgctttgact 840
cctcacccac ctcaaaagca agcctacggt gttaccttgc ccacttctgt cttgttcatt 900
gccggtcacg atactaactt ggcaaatctc ggcggtgctt tggagttgaa ctggactctt 960
cctggtcaac ctgataacac tccaccaggt ggtgagctcg ttttcgaaag atggcgtaga 1020
ctatctgata actcttgttg gattcaggtt tcgttggtct tccaaacttt gcagcagatg 1080
agagacaaga ctccatgttc tttgaacacg cctccaggag aagtcaaatt gaccttggct 1140
ggatgtgaag agagaaatgc tcagggtatg tgttcctgtg ctggtttcac tcaaatcgtt 1200
aacgaagcta gaatcccagc ttgttccttg tag 1233
<210> 64
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPA-M1-DMO
<400> 64
cagagtgagc ctgagttgaa actggaatcc gttgtcatcg tctctagaca tggtgttaga 60
gcaccaacca agttcaccca acttatgcaa gatgtcaccc cagacgcttg gccaacctgg 120
ccagtcaagc tgggtgaatt gacacctaga ggtggtgagc tcattgctta cttgggtcac 180
tgttggagac agcgtcttgt tgccgacgaa ttgttgccta agtgtggttg tccacaatct 240
ggtcaagtag ctattattgc tgacgtcgac gaaagaaccc gtaagacagg tgaagccttc 300
gccgccggtc ttgctcctga ctgtgccatt accgttcacc atcaagctga cacttcttct 360
ccagatccat tgttcaaccc tttgaagact ggtgtttgcc aattggacgt tgctaacgtt 420
actagagcta tcttggaaag agctggagga tctattgctg acttcaccgg tcactaccag 480
actgccttca gagagttgga aagagttctt aacttcccac aatccaactt gtgccttaag 540
cgtgagaagc aagacgaatc ctgttccttg actcaagcat taccatctga gttgaaggtc 600
tccgccgaca acgtctcttt gaccggtgct gtcagcttgg cttccatgtt gactgaaatc 660
tttcttctgc aacaagctca aggtatgcct gagccaggtt ggggtagaat caccgactct 720
caccaatgga acaccttgtt gtccttgcac aacgctcaat tcgatttgct gcagagaact 780
ccagaggttg ctagatccag agccacccca ttgttggact tgatcaagac tgctttgact 840
cctcacccac ctcaaaagca agcctacggt gttaccttgc ccacttctgt cttgttcatt 900
gccggtcacg atactaactt ggcaaatctc ggcggtgctt tgtgtttgaa ctggactctt 960
cctggtcaac ctgataacac tccaccaggt ggtgagctcg ttttcgaaag atggcgtaga 1020
ctatctgata actcttgttg gattcaggtt tcgttggtct tccaaacttt gcagcagatg 1080
agagacaaga ctccatgttc tttgaacacg cctccaggag aagtcaaatt gaccttgtgt 1140
ggatgtgaag agagaaatgc tcagggtatg tgttcctgtg ctggtttcac tcaaatcgtt 1200
aacgaagcta gaatcccagc ttgttccttg tag 1233
<210> 65
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPAan-A
<400> 65
cagtccgagc ccgagctcaa gctcgagtcc gtcgtcatcg tctcccgcca cggtgtccgc 60
gcccccacca aggccaccca gctcatgcag gacgtcacct gcgacgcctg gcccacctgg 120
cccgtcaagc tcggttggct caccccccgc ggtggtgagc tcatcgccta cctcggtcac 180
taccagcgcc agcgcctcgt cgccgacggt ctcctcgcca agaagggttg cccccagtcc 240
ggtcaggtcg ccatcatcgc cgacgtcgac gagcgcaccc gcaagaccgg tgaggccttc 300
gccgccggtc tcgcccccga ctgcgccatc accgtccaca cccaggccga cacctcctcc 360
cccgaccccc tcttcaaccc cctcaagacc ggtgtctgcc agctcgacaa cgccaacgtc 420
accgacgcca tcctctcccg cgccggtggt tccatcgccg acttcaccgg tcaccgccag 480
accgccttcc gcgagctcga gcgcgtcctc aacttcccct gctccaacct ctgcctcaag 540
cgcgagaagc aggacgagtc ctgctccctc acccaggccc tcccctccga gctcaaggtc 600
tccgccgaca acgtctccct caccggtgcc gtctccctcg cctccatgct caccgagatc 660
ttcctcctcc agcaggccca gggtatgccc gagcccggtt ggggtcgcat caccgactcc 720
caccagtgga acaccctcct ctccctccac aacgcccagt tctacctcct ccagcgcacc 780
cccgaggtcg cccgctcccg cgccaccccc ctcctcgacc tcatcaagac cgccctcacc 840
ccccaccccc cccagaagca ggcctacggt gtcaccctcc ccacctccgt cctcttcatc 900
gccggtcacg acaccaacct cgccaacctc ggtggtgccc tcgagctcaa ctggaccctc 960
cccggtcagc ccgacaacac cccccccggt ggtgagctcg tcttcgagcg ctggcgccgc 1020
ctctccgaca actcccagtg gatccaggtc tccctcgtct tccagaccct ccagcagatg 1080
cgcgacaaga cccccctctc cctcaacacc ccccccggtg aggtcaagct caccctcgcc 1140
ggttgcgagg agcgcaacgc ccagggtatg tgctccctcg ccggtttcac ccagatcgtc 1200
aacgaggccc gcatccccgc ctgctccctc taa 1233
<210> 66
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPAan-B
<400> 66
cagtccgagc ccgagctcaa gctcgagtcc gtcgtcatcg tctcccgcca cggtgtccgc 60
gcccccacca aggccaccca gctcatgcag gacgtcaccc ccgacgcctg gcccacctgg 120
cccgtcaagc tcggttggct caccccccgc ggtggtgagc tcatctgcta cctcggtcac 180
taccagcgcc agcgcctcgt cgccgacggt ctcctcgcca agaagggttg cccccagtcc 240
ggtcaggtcg ccatcatcgc cgacgtcgac gagcgcaccc gcaagaccgg tgaggccttc 300
gccgcctgcc tcgcccccga ctgcgccatc accgtccaca cccaggccga cacctcctcc 360
cccgaccccc tcttcaaccc cctcaagacc ggtgtctgcc agctcgacaa cgccaacgtc 420
accgacgcca tcctctcccg cgccggtggt tccatcgccg acttcaccgg tcaccgccag 480
accgccttcc gcgagctcga gcgcgtcctc aacttccccc agtccaacct ctgcctcaag 540
cgcgagaagc aggacgagtc ctgctccctc acccaggccc tcccctccga gctcaaggtc 600
tccgccgaca acgtctccct caccggtgcc gtctccctcg cctccatgct caccgagatc 660
ttcctcctcc agcaggccca gggtatgccc gagcccggtt ggggtcgcat caccgactcc 720
caccagtgga acaccctcct ctccctccac aacgcccagt tctacctcct ccagcgcacc 780
cccgaggtcg cccgctcccg cgccaccccc ctcctcgacc tcatcaagac cgccctcacc 840
ccccaccccc cccagaagca ggcctacggt gtcaccctcc ccacctccgt cctcttcatc 900
gccggtcacg acaccaacct cgccaacctc ggtggtgccc tcgagctcaa ctggaccctc 960
cccggtcagc ccgacaacac cccccccggt ggtgagctcg tcttcgagcg ctggcgccgc 1020
ctctccgaca actcccagtg gatccaggtc tccctcgtct tccagaccct ccagcagatg 1080
cgcgacaaga cccccctctc cctcaacacc ccccccggtg aggtcaagct caccctcgcc 1140
ggttgcgagg agcgcaacgc ccagggtatg tgctccctcg ccggtttcac ccagatcgtc 1200
aacgaggccc gcatccccgc ctgctccctc taa 1233
<210> 67
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPAan-C
<400> 67
cagtccgagc ccgagctcaa gctcgagtcc gtcgtcatcg tctcccgcca cggtgtccgc 60
gcccccacca aggccaccca gctcatgcag gacgtcaccc ccgacgcctg gcccacctgg 120
cccgtcaagc tcggttggct caccccccgc ggtggtgagc tcatcgcctg cctcggtcac 180
taccagcgcc agcgcctcgt cgccgacggt ctcctcgcca agaagggttg cccccagtcc 240
ggtcaggtcg ccatcatcgc cgacgtcgac gagcgcaccc gcaagaccgg tgaggccttc 300
gccgccggtc tcgcccccga ctgcgccatc accgtccaca cccaggccga cacctcctcc 360
cccgaccccc tcttcaaccc cctcaagacc ggtgtctgcc agctcgacaa cgccaacgtc 420
accgacgcca tcctctcccg cgccggtggt tccatcgccg acttcaccgg tcaccgccag 480
accgccttcc gcgagctcga gcgcgtcctc aacttccccc agtccaacct ctgcctcaag 540
cgcgagaagc aggacgagtc ctgctccctc acccaggccc tcccctccga gctcaaggtc 600
tccgccgaca acgtctccct caccggtgcc gtctccctcg cctccatgct caccgagatc 660
ttcctcctcc agcaggccca gggtatgccc gagcccggtt ggggtcgcat caccgactcc 720
caccagtgga acaccctcct ctccctccac aacgcccagt tctacctcct ccagcgcacc 780
cccgaggtcg cccgctcccg cgccaccccc ctcctcgacc tcatcaagac cgccctcacc 840
ccccaccccc cccagaagca ggcctacggt gtcaccctcc ccacctccgt cctcttcatc 900
gccggtcacg acaccaacct cgccaacctc ggtggtgccc tcgagctcaa ctggaccctc 960
cccggtcagc ccgacaacac cccccccggt ggtgagctcg tcttcgagcg ctggcgccgc 1020
ctctccgaca actcccagtg gatccaggtc tccctcgtct tccagaccct ccagcagatg 1080
cgcgacaaga ccccctgctc cctcaacacc ccccccggtg aggtcaagct caccctcgcc 1140
ggttgcgagg agcgcaacgc ccagggtatg tgctccctcg ccggtttcac ccagatcgtc 1200
aacgaggccc gcatccccgc ctgctccctc taa 1233
<210> 68
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPAan-D
<400> 68
cagtccgagc ccgagctcaa gctcgagtcc gtcgtcatcg tctcccgcca cggtgtccgc 60
gcccccacca aggccaccca gctcatgcag gacgtcaccc ccgacgcctg gcccacctgg 120
cccgtcaagc tcggttggct caccccccgc ggtggtgagc tcatcgccta cctcggtcac 180
tgccagcgcc agcgcctcgt cgccgacggt ctcctcgcca agaagggttg cccccagtcc 240
ggtcaggtcg ccatcatcgc cgacgtcgac gagcgcaccc gcaagaccgg tgaggccttc 300
gccgccggtc tcgcccccga ctgcgccatc accgtccaca cccaggccga cacctcctcc 360
cccgaccccc tcttcaaccc cctcaagacc ggtgtctgcc agctcgacaa cgccaacgtc 420
accgacgcca tcctctcccg cgccggtggt tccatcgccg acttcaccgg tcaccgccag 480
accgccttcc gcgagctcga gcgcgtcctc aacttccccc agtccaacct ctgcctcaag 540
cgcgagaagc aggacgagtc ctgctccctc acccaggccc tcccctccga gctcaaggtc 600
tccgccgaca acgtctccct caccggtgcc gtctccctcg cctccatgct caccgagatc 660
ttcctcctcc agcaggccca gggtatgccc gagcccggtt ggggtcgcat caccgactcc 720
caccagtgga acaccctcct ctccctccac aacgcccagt tctacctcct ccagcgcacc 780
cccgaggtcg cccgctcccg cgccaccccc ctcctcgacc tcatcaagac cgccctcacc 840
ccccaccccc cccagaagca ggcctacggt gtcaccctcc ccacctccgt cctcttcatc 900
gccggtcacg acaccaacct cgccaacctc ggtggtgccc tcgagctcaa ctggaccctc 960
cccggtcagc ccgacaacac cccccccggt ggtgagctcg tcttcgagcg ctggcgccgc 1020
ctctccgaca actcccagtg gatccaggtc tccctcgtct tccagaccct ccagcagatg 1080
cgcgacaaga ccccctgctc cctcaacacc ccccccggtg aggtcaagct caccctcgcc 1140
ggttgcgagg agcgcaacgc ccagggtatg tgctccctcg ccggtttcac ccagatcgtc 1200
aacgaggccc gcatccccgc ctgctccctc taa 1233
<210> 69
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPAan-E
<400> 69
cagtccgagc ccgagctcaa gctcgagtcc gtcgtcatcg tctcccgcca cggtgtccgc 60
gcccccacca aggccaccca gctcatgcag gacgtcaccc ccgacgcctg gcccacctgg 120
cccgtcaagc tcggttggct caccccccgc ggtggtgagc tcatcgccta cctcggtcac 180
taccagcgcc agcgcctcgt cgccgacggt ctcctcgcca agaagggttg cccccagtcc 240
ggttgcgtcg ccatcatcgc cgacgtcgac gagcgcaccc gcaagaccgg tgaggccttc 300
gccgccggtc tcgcccccga ctgcgccatc accgtccaca cccaggccga cacctcctcc 360
cccgaccccc tcttcaaccc cctcaagacc ggtgtctgcc agctcgacaa cgccaacgtc 420
accgacgcca tcctctcccg cgccggtggt tccatcgccg acttcaccgg tcaccgccag 480
accgccttcc gcgagctcga gcgcgtcctc aacttccccc agtccaacct ctgcctcaag 540
cgcgagaagc aggacgagtc ctgctccctc acccaggccc tcccctccga gctcaaggtc 600
tccgccgaca acgtctccct caccggtgcc gtctccctcg cctccatgct caccgagatc 660
ttcctcctcc agcaggccca gggtatgccc gagcccggtt ggggtcgcat caccgactcc 720
caccagtgga acaccctcct ctccctccac aacgcccagt tctacctcct ccagcgcacc 780
cccgaggtcg cccgctcccg cgccaccccc ctcctcgacc tcatcaagac cgccctcacc 840
ccccaccccc cccagaagca ggcctacggt gtcaccctcc ccacctgcgt cctcttcatc 900
gccggtcacg acaccaacct cgccaacctc ggtggtgccc tcgagctcaa ctggaccctc 960
cccggtcagc ccgacaacac cccccccggt ggtgagctcg tcttcgagcg ctggcgccgc 1020
ctctccgaca actcccagtg gatccaggtc tccctcgtct tccagaccct ccagcagatg 1080
cgcgacaaga cccccctctc cctcaacacc ccccccggtg aggtcaagct caccctcgcc 1140
ggttgcgagg agcgcaacgc ccagggtatg tgctccctcg ccggtttcac ccagatcgtc 1200
aacgaggccc gcatccccgc ctgctccctc taa 1233
<210> 70
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPAan-F
<400> 70
cagtccgagc ccgagctcaa gctcgagtcc gtcgtcatcg tctcccgcca cggtgtccgc 60
gcccccacca aggccaccca gctcatgcag gacgtcaccc ccgacgcctg gcccacctgg 120
cccgtcaagc tcggttggct caccccccgc ggtggtgagc tcatcgccta cctcggtcac 180
taccagcgcc agcgcctcgt cgccgacggt ctcctcgcca agaagggttg cccccagtcc 240
ggtcaggtcg ccatcatcgc cgacgtcgac gagcgcaccc gcaagaccgg tgaggccttc 300
gccgccggtc tcgcccccga ctgcgccatc accgtccaca cccaggccga cacctcctcc 360
cccgaccccc tcttcaaccc ctgcaagacc ggtgtctgcc agctcgacaa cgccaacgtc 420
accgacgcca tcctctcccg cgccggtggt tccatcgccg acttcaccgg tcaccgccag 480
accgccttcc gcgagctcga gcgcgtcctc aacttccccc agtccaacct ctgcctcaag 540
cgcgagaagc aggacgagtc ctgctccctc acccaggccc tcccctccga gctcaaggtc 600
tccgcctgca acgtctccct caccggtgcc gtctccctcg cctccatgct caccgagatc 660
ttcctcctcc agcaggccca gggtatgccc gagcccggtt ggggtcgcat caccgactcc 720
caccagtgga acaccctcct ctccctccac aacgcccagt tctacctcct ccagcgcacc 780
cccgaggtcg cccgctcccg cgccaccccc ctcctcgacc tcatcaagac cgccctcacc 840
ccccaccccc cccagaagca ggcctacggt gtcaccctcc ccacctccgt cctcttcatc 900
gccggtcacg acaccaacct cgccaacctc ggtggtgccc tcgagctcaa ctggaccctc 960
cccggtcagc ccgacaacac cccccccggt ggtgagctcg tcttcgagcg ctggcgccgc 1020
ctctccgaca actcccagtg gatccaggtc tccctcgtct tccagaccct ccagcagatg 1080
cgcgacaaga cccccctctc cctcaacacc ccccccggtg aggtcaagct caccctcgcc 1140
ggttgcgagg agcgcaacgc ccagggtatg tgctccctcg ccggtttcac ccagatcgtc 1200
aacgaggccc gcatccccgc ctgctccctc taa 1233
<210> 71
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPAan-I
<400> 71
cagtccgagc ccgagctcaa gctcgagtcc gtcgtcatcg tctcccgcca cggtgtccgc 60
gcccccacca aggccaccca gctcatgcag gacgtcaccc ccgacgcctg gcccacctgg 120
cccgtcaagc tcggttggct caccccccgc ggtggtgagc tcatcgccta cctcggtcac 180
taccagcgcc agcgcctcgt cgccgacggt ctcctcgcca agaagggttg cccccagtcc 240
ggtcaggtcg ccatcatcgc cgacgtcgac gagcgcaccc gcaagaccgg tgaggccttc 300
gccgccggtc tcgcccccga ctgcgccatc accgtccaca cccaggccga cacctcctcc 360
cccgaccccc tcttcaaccc cctcaagacc ggtgtctgcc agctcgacaa cgccaacgtc 420
accgacgcca tcctctcccg cgccggtggt tccatcgccg acttcaccgg tcaccgccag 480
accgccttcc gctgcctcga gcgcgtcctc aacttccccc agtccaacct ctgcctcaag 540
cgcgagaagc aggacgagtc ctgctccctc acccaggccc tcccctccga gctcaaggtc 600
tccgccgaca acgtctccct caccggtgcc gtctccctcg cctccatgct caccgagatc 660
ttcctcctcc agcaggccca gggtatgccc gagcccggtt ggggtcgcat caccgactcc 720
caccagtgga actgcctcct ctccctccac aacgcccagt tctacctcct ccagcgcacc 780
cccgaggtcg cccgctcccg cgccaccccc ctcctcgacc tcatcaagac cgccctcacc 840
ccccaccccc cccagaagca ggcctacggt gtcaccctcc ccacctccgt cctcttcatc 900
gccggtcacg acaccaacct cgccaacctc ggtggtgccc tcgagctcaa ctggaccctc 960
cccggtcagc ccgacaacac cccccccggt ggtgagctcg tcttcgagcg ctggcgccgc 1020
ctctccgaca actcccagtg gatccaggtc tccctcgtct tccagaccct ccagcagatg 1080
cgcgacaaga cccccctctc cctcaacacc ccccccggtg aggtcaagct caccctcgcc 1140
ggttgcgagg agcgcaacgc ccagggtatg tgctccctcg ccggtttcac ccagatcgtc 1200
aacgaggccc gcatccccgc ctgctccctc taa 1233
<210> 72
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPAan-J
<400> 72
cagtccgagc ccgagctcaa gctcgagtcc gtcgtcatcg tctcccgcca cggtgtccgc 60
gcccccacca aggccaccca gctcatgcag gacgtcaccc ccgacgcctg gcccacctgg 120
cccgtcaagc tcggttggct caccccccgc ggtggtgagc tcatcgccta cctcggtcac 180
taccagcgcc agcgcctcgt cgccgacggt ctcctcgcca agaagggttg cccccagtcc 240
ggtcaggtcg ccatcatcgc cgacgtcgac gagcgcaccc gcaagaccgg tgaggccttc 300
gccgccggtc tcgcccccga ctgcgccatc accgtccaca cccaggccga cacctcctcc 360
cccgaccccc tcttcaaccc cctcaagacc ggtgtctgcc agctcgacaa cgccaacgtc 420
accgacgcca tcctctcccg cgccggtggt tccatcgccg acttcaccgg tcaccgccag 480
accgccttcc gcgagctcga gcgcgtcctc aacttccccc agtccaacct ctgcctcaag 540
cgcgagaagc aggacgagtc ctgctccctc tgccaggccc tcccctccga gctcaaggtc 600
tccgccgaca acgtctccct caccggtgcc gtctccctcg cctccatgct caccgagatc 660
ttcctcctcc agcaggccca gggtatgccc gagcccggtt ggggtcgcat caccgactgc 720
caccagtgga acaccctcct ctccctccac aacgcccagt tctacctcct ccagcgcacc 780
cccgaggtcg cccgctcccg cgccaccccc ctcctcgacc tcatcaagac cgccctcacc 840
ccccaccccc cccagaagca ggcctacggt gtcaccctcc ccacctccgt cctcttcatc 900
gccggtcacg acaccaacct cgccaacctc ggtggtgccc tcgagctcaa ctggaccctc 960
cccggtcagc ccgacaacac cccccccggt ggtgagctcg tcttcgagcg ctggcgccgc 1020
ctctccgaca actcccagtg gatccaggtc tccctcgtct tccagaccct ccagcagatg 1080
cgcgacaaga cccccctctc cctcaacacc ccccccggtg aggtcaagct caccctcgcc 1140
ggttgcgagg agcgcaacgc ccagggtatg tgctccctcg ccggtttcac ccagatcgtc 1200
aacgaggccc gcatccccgc ctgctccctc taa 1233
<210> 73
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPAan-K
<400> 73
cagtccgagc ccgagctcaa gctcgagtcc gtcgtcatcg tctcccgcca cggtgtccgc 60
gcccccacca aggccaccca gctcatgcag gacgtcaccc ccgacgcctg gcccacctgg 120
cccgtcaagc tcggttggct caccccccgc ggtggtgagc tcatcgccta cctcggtcac 180
taccagcgcc agcgcctcgt cgccgacggt ctcctcgcca agaagggttg cccccagtcc 240
ggtcaggtcg ccatcatcgc cgacgtcgac gagcgcaccc gcaagaccgg tgaggccttc 300
gccgccggtc tcgcccccga ctgcgccatc accgtccaca cccaggccga cacctcctcc 360
cccgaccccc tcttcaaccc cctcaagacc ggtgtctgcc agctcgacaa cgccaacgtc 420
accgacgcca tcctctcccg cgccggtggt tccatcgccg acttcaccgg tcaccgccag 480
accgccttcc gcgagctcga gcgcgtcctc aacttccccc agtccaacct ctgcctcaag 540
cgcgagaagc aggacgagtc ctgctccctc acccaggccc tcccctgcga gctcaaggtc 600
tccgccgaca acgtctccct caccggtgcc tgctccctcg cctccatgct caccgagatc 660
ttcctcctcc agcaggccca gggtatgccc gagcccggtt ggggtcgcat caccgactcc 720
caccagtgga acaccctcct ctccctccac aacgcccagt tctacctcct ccagcgcacc 780
cccgaggtcg cccgctcccg cgccaccccc ctcctcgacc tcatcaagac cgccctcacc 840
ccccaccccc cccagaagca ggcctacggt gtcaccctcc ccacctccgt cctcttcatc 900
gccggtcacg acaccaacct cgccaacctc ggtggtgccc tcgagctcaa ctggaccctc 960
cccggtcagc ccgacaacac cccccccggt ggtgagctcg tcttcgagcg ctggcgccgc 1020
ctctccgaca actcccagtg gatccaggtc tccctcgtct tccagaccct ccagcagatg 1080
cgcgacaaga cccccctctc cctcaacacc ccccccggtg aggtcaagct caccctcgcc 1140
ggttgcgagg agcgcaacgc ccagggtatg tgctccctcg ccggtttcac ccagatcgtc 1200
aacgaggccc gcatccccgc ctgctccctc taa 1233
<210> 74
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPAan-L
<400> 74
cagtccgagc ccgagctcaa gctcgagtcc gtcgtcatcg tctcccgcca cggtgtccgc 60
gcccccacca aggccaccca gctcatgcag gacgtcaccc ccgacgcctg gcccacctgg 120
cccgtcaagc tcggttggct caccccccgc ggtggtgagc tcatcgccta cctcggtcac 180
taccagcgcc agcgcctcgt cgccgacggt ctcctcgcca agaagggttg cccccagtcc 240
ggtcaggtcg ccatcatcgc cgacgtcgac gagcgcaccc gcaagaccgg tgaggccttc 300
gccgccggtc tcgcccccga ctgcgccatc accgtccaca cccaggccga cacctcctcc 360
cccgaccccc tcttcaaccc cctcaagacc ggtgtctgcc agctcgacaa cgccaacgtc 420
accgacgcca tcctctcccg cgccggtggt tccatcgccg acttcaccgg tcaccgccag 480
accgccttcc gcgagctcga gcgcgtcctc aacttccccc agtccaacct ctgcctcaag 540
cgcgagaagc aggacgagtc ctgctccctc acccaggccc tcccctccga gctcaaggtc 600
tccgccgaca acgtctccct caccggtgcc gtctccctcg cctccatgct caccgagatc 660
ttcctcctcc agcaggccca gggtatgccc gagcccggtt ggggtcgcat caccgactcc 720
caccagtgga acaccctcct ctccctccac aacgcccagt tctacctcct ccagcgcacc 780
cccgaggtct gccgctcccg cgccaccccc ctcctcgacc tcatcaagac cgccctcacc 840
ccccaccccc cccagaagca ggcctacggt gtcaccctcc ccacctccgt cctcttcatc 900
gccggtcacg acaccaacct cgccaacctc ggttgcgccc tcgagctcaa ctggaccctc 960
cccggtcagc ccgacaacac cccccccggt ggtgagctcg tcttcgagcg ctggcgccgc 1020
ctctccgaca actcccagtg gatccaggtc tccctcgtct tccagaccct ccagcagatg 1080
cgcgacaaga cccccctctc cctcaacacc ccccccggtg aggtcaagct caccctcgcc 1140
ggttgcgagg agcgcaacgc ccagggtatg tgctccctcg ccggtttcac ccagatcgtc 1200
aacgaggccc gcatccccgc ctgctccctc taa 1233
<210> 75
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPAan-M
<400> 75
cagtccgagc ccgagctcaa gctcgagtcc gtcgtcatcg tctcccgcca cggtgtccgc 60
gcccccacca aggccaccca gctcatgcag gacgtcaccc ccgacgcctg gcccacctgg 120
cccgtcaagc tcggttggct caccccccgc ggtggtgagc tcatcgccta cctcggtcac 180
taccagcgcc agcgcctcgt cgccgacggt ctcctcgcca agaagggttg cccccagtcc 240
ggtcaggtcg ccatcatcgc cgacgtcgac gagcgcaccc gcaagaccgg tgaggccttc 300
gccgccggtc tcgcccccga ctgcgccatc accgtccaca cccaggccga cacctcctcc 360
cccgaccccc tcttcaaccc cctcaagacc ggtgtctgcc agctcgacaa cgccaacgtc 420
accgacgcca tcctctcccg cgccggtggt tccatcgccg acttcaccgg tcaccgccag 480
accgccttcc gcgagctcga gcgcgtcctc aacttccccc agtccaacct ctgcctcaag 540
cgcgagaagc aggacgagtc ctgctccctc acccaggccc tcccctccga gctcaaggtc 600
tccgccgaca acgtctccct caccggtgcc gtctccctcg cctccatgct caccgagatc 660
ttcctcctcc agcaggccca gggtatgccc gagcccggtt ggggtcgcat caccgactcc 720
caccagtgga acaccctcct ctccctccac aacgcccagt tctacctcct ccagcgcacc 780
cccgaggtcg cccgctcccg cgccaccccc ctcctcgacc tcatcaagac cgccctcacc 840
ccccaccccc cccagaagca ggcctacggt gtcaccctcc ccacctccgt cctcttcatc 900
gccggtcacg acaccaacct cgccaacctc ggtggtgccc tctgcctcaa ctggaccctc 960
cccggtcagc ccgacaacac cccccccggt ggtgagctcg tcttcgagcg ctggcgccgc 1020
ctctccgaca actcccagtg gatccaggtc tccctcgtct tccagaccct ccagcagatg 1080
cgcgacaaga cccccctctc cctcaacacc ccccccggtg aggtcaagct caccctctgc 1140
ggttgcgagg agcgcaacgc ccagggtatg tgctccctcg ccggtttcac ccagatcgtc 1200
aacgaggccc gcatccccgc ctgctccctc taa 1233
<210> 76
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPAan-N
<400> 76
cagtccgagc ccgagctcaa gctcgagtcc gtcgtcatcg tctcccgcca cggtgtccgc 60
gcccccacca aggccaccca gctcatgcag gacgtcaccc ccgacgcctg gcccacctgg 120
cccgtcaagc tcggttggct caccccccgc ggtggtgagc tcatcgccta cctcggtcac 180
taccagcgcc agcgcctcgt cgccgacggt ctcctcgcca agaagggttg cccccagtcc 240
ggtcaggtcg ccatcatcgc cgacgtcgac gagcgcaccc gcaagaccgg tgaggccttc 300
gccgccggtc tcgcccccga ctgcgccatc accgtccaca cccaggccga cacctcctcc 360
cccgaccccc tcttcaaccc cctcaagacc ggtgtctgcc agctcgacaa cgccaacgtc 420
accgacgcca tcctctcccg cgccggtggt tccatcgccg acttcaccgg tcaccgccag 480
accgccttcc gcgagctcga gcgcgtcctc aacttccccc agtccaacct ctgcctcaag 540
cgcgagaagc aggacgagtc ctgctccctc acccaggccc tcccctccga gctcaaggtc 600
tccgccgaca acgtctccct caccggtgcc gtctccctcg cctccatgct caccgagatc 660
ttcctcctcc agcaggccca gggtatgccc gagcccggtt ggggtcgcat caccgactcc 720
caccagtgga acaccctcct ctccctccac aacgcccagt tctacctcct ccagcgcacc 780
cccgaggtcg cccgctcccg cgccaccccc ctcctcgacc tcatcaagac cgccctcacc 840
ccccaccccc cccagaagca ggcctacggt gtcaccctcc ccacctccgt cctcttcatc 900
gccggtcacg acaccaacct cgccaacctc ggtggtgccc tcgagctcaa ctggaccctc 960
ccctgccagc ccgacaacac cccccccggt ggtgagctcg tcttcgagcg ctggcgccgc 1020
ctctccgaca actcccagtg gatccaggtc tccctcgtct tccagtgcct ccagcagatg 1080
cgcgacaaga cccccctctc cctcaacacc ccccccggtg aggtcaagct caccctcgcc 1140
ggttgcgagg agcgcaacgc ccagggtatg tgctccctcg ccggtttcac ccagatcgtc 1200
aacgaggccc gcatccccgc ctgctccctc taa 1233
<210> 77
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPAan-O
<400> 77
cagtccgagc ccgagctcaa gctcgagtcc gtcgtcatcg tctcccgcca cggtgtccgc 60
gcccccacca aggccaccca gctcatgcag gacgtcaccc ccgacgcctg gcccacctgg 120
cccgtcaagc tcggttggct caccccccgc ggtggtgagc tcatcgccta cctcggtcac 180
taccagcgcc agcgcctcgt cgccgacggt ctcctcgcca agaagggttg cccccagtcc 240
ggtcaggtcg ccatcatcgc cgacgtcgac gagcgcaccc gcaagaccgg tgaggccttc 300
gccgccggtc tcgcccccga ctgcgccatc accgtccaca cccaggccga cacctcctcc 360
cccgaccccc tcttcaaccc cctcaagacc ggtgtctgcc agctcgacaa cgccaacgtc 420
accgacgcca tcctctcccg cgccggtggt tccatcgccg acttcaccgg tcaccgccag 480
accgccttcc gcgagctcga gcgcgtcctc aacttccccc agtccaacct ctgcctcaag 540
cgcgagaagc aggacgagtc ctgctccctc acccaggccc tcccctccga gctcaaggtc 600
tccgccgaca acgtctccct caccggtgcc gtctccctcg cctccatgct caccgagatc 660
ttcctcctcc agcaggccca gggtatgccc gagcccggtt ggggtcgcat caccgactcc 720
caccagtgga acaccctcct ctccctccac aacgcccagt tctacctcct ccagcgcacc 780
cccgaggtcg cccgctcccg cgccaccccc ctcctcgacc tcatcaagac cgccctcacc 840
ccccaccccc cccagaagca ggcctacggt gtcaccctcc ccacctccgt cctcttcatc 900
gccggtcacg acaccaacct cgccaacctc ggtggtgccc tcgagctcaa ctggaccctc 960
cccggtcagc ccgacaacac cccccccggt ggtgagctcg tcttcgagcg ctggcgccgc 1020
ctctccgaca actcctgctg gatccaggtc tccctcgtct tccagaccct ccagcagatg 1080
cgcgacaaga cccccctctc cctcaacacc ccccccggtg aggtcaagct caccctcgcc 1140
ggttgcgagg agcgcaacgc ccagggtatg tgctcctgcg ccggtttcac ccagatcgtc 1200
aacgaggccc gcatccccgc ctgctccctc taa 1233
<210> 78
<211> 1233
<212> DNA
<213> Aspergillus niger
<400> 78
cagagtgagc ctgagttgaa actggaatcc gttgtcatcg tctctagaca tggtgttaga 60
gcaccaacca aggccaccca acttatgcaa gatgtcaccc cagacgcttg gccaacctgg 120
ccagtcaagc tgggttggtt gacacctaga ggtggtgagc tcattgctta cttgggtcac 180
taccaaagac agcgtcttgt tgccgacgga ttgttggcca agaagggttg tccacaatct 240
ggtcaagtag ctattattgc tgacgtcgac gaaagaaccc gtaagacagg tgaagccttc 300
gccgccggtc ttgctcctga ctgtgccatt accgttcaca cccaagctga cacttcttct 360
ccagatccat tgttcaaccc tttgaagact ggtgtttgcc aattggacaa cgctaacgtt 420
actgacgcta tcttgtccag agctggagga tccattgctg acttcaccgg tcacagacag 480
actgccttca gagagttgga aagagttctt aacttcccac aatcaaactt gtgcttgaag 540
cgtgagaagc aagacgaatc ctgttccttg actcaagcat taccatctga gttgaaggtc 600
tccgccgaca acgtctcttt gaccggtgct gtcagcttgg cttccatgtt gactgaaatc 660
tttcttctgc aacaagctca aggtatgcct gagccaggtt ggggtagaat caccgactct 720
caccaatgga acaccttgtt gtccttgcac aacgctcaat tctacttgct gcagagaact 780
ccagaggttg ctagatccag agccacccca ttgttggact tgatcaagac tgctttgact 840
cctcacccac ctcaaaagca agcctacggt gttaccttgc ccacttctgt cttgttcatt 900
gccggtcacg atactaactt ggcaaatctc ggcggtgctt tggagttgaa ctggactctt 960
cctggtcaac ctgataacac tccaccaggt ggtgagctcg ttttcgaaag atggcgtaga 1020
ctatctgata actctcaatg gattcaggtt tcgttggtct tccaaacttt gcagcagatg 1080
agagacaaga ctccactgtc tttgaacacg cctccaggag aagtcaaatt gaccttggct 1140
ggatgtgaag agagaaatgc tcagggtatg tgttccttgg ctggtttcac tcaaatcgtt 1200
aacgaagcta gaatcccagc ttgttccttg tag 1233
<210> 79
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPA-M2
<400> 79
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Ala Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Glu Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Ala Tyr Leu Gly His Tyr Trp Arg Gln
50 55 60
Arg Leu Val Ala Asp Glu Leu Leu Pro Asn Gln Thr Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Gly Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His Thr Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Asn Ala Asn Val Thr Asp Ala Ile
130 135 140
Leu Glu Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Tyr Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Ser Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Asp Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro Asn Gly Thr Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Glu Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Gln Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Leu Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Ala Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Leu Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 80
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> AAPA-M2-B
<400> 80
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Ala Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Glu Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Cys Tyr Leu Gly His Tyr Trp Arg Gln
50 55 60
Arg Leu Val Ala Asp Glu Leu Leu Pro Asn Gln Thr Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Cys Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His Thr Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Asn Ala Asn Val Thr Asp Ala Ile
130 135 140
Leu Glu Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Tyr Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Ser Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Asp Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro Asn Gly Thr Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Glu Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Gln Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Leu Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Ala Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Leu Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 81
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPA-M2-C
<400> 81
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Ala Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Glu Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Ala Cys Leu Gly His Tyr Trp Arg Gln
50 55 60
Arg Leu Val Ala Asp Glu Leu Leu Pro Asn Gln Thr Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Gly Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His Thr Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Asn Ala Asn Val Thr Asp Ala Ile
130 135 140
Leu Glu Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Tyr Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Ser Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Asp Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro Asn Gly Thr Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Glu Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Gln Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Cys Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Ala Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Leu Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 82
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPA-M2-D
<400> 82
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Ala Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Glu Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Ala Tyr Leu Gly His Cys Trp Arg Gln
50 55 60
Arg Leu Val Ala Asp Glu Leu Leu Pro Asn Gln Thr Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Gly Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His Thr Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Asn Ala Asn Val Thr Asp Ala Ile
130 135 140
Leu Glu Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Tyr Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Ser Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Asp Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro Asn Gly Thr Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Glu Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Gln Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Cys Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Ala Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Leu Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 83
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPA-M2-M
<400> 83
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Ala Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Glu Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Ala Tyr Leu Gly His Tyr Trp Arg Gln
50 55 60
Arg Leu Val Ala Asp Glu Leu Leu Pro Asn Gln Thr Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Gly Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His Thr Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Asn Ala Asn Val Thr Asp Ala Ile
130 135 140
Leu Glu Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Tyr Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Ser Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Asp Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro Asn Gly Thr Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Cys Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Gln Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Leu Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Cys Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Leu Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 84
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPA-M2-O
<400> 84
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Ala Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Glu Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Ala Tyr Leu Gly His Tyr Trp Arg Gln
50 55 60
Arg Leu Val Ala Asp Glu Leu Leu Pro Asn Gln Thr Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Gly Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His Thr Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Asn Ala Asn Val Thr Asp Ala Ile
130 135 140
Leu Glu Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Tyr Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Ser Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Asp Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro Asn Gly Thr Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Glu Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Cys Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Leu Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Ala Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Cys Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 85
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPA-M2-BO
<400> 85
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Ala Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Glu Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Cys Tyr Leu Gly His Tyr Trp Arg Gln
50 55 60
Arg Leu Val Ala Asp Glu Leu Leu Pro Asn Gln Thr Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Cys Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His Thr Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Asn Ala Asn Val Thr Asp Ala Ile
130 135 140
Leu Glu Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Tyr Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Ser Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Asp Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro Asn Gly Thr Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Glu Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Cys Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Leu Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Ala Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Cys Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 86
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPA-M2-DO
<400> 86
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Ala Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Glu Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Ala Tyr Leu Gly His Cys Trp Arg Gln
50 55 60
Arg Leu Val Ala Asp Glu Leu Leu Pro Asn Gln Thr Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Gly Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His Thr Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Asn Ala Asn Val Thr Asp Ala Ile
130 135 140
Leu Glu Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Tyr Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Ser Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Asp Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro Asn Gly Thr Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Glu Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Cys Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Cys Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Ala Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Cys Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 87
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPA-M2-MO
<400> 87
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Ala Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Glu Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Ala Tyr Leu Gly His Tyr Trp Arg Gln
50 55 60
Arg Leu Val Ala Asp Glu Leu Leu Pro Asn Gln Thr Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Gly Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His Thr Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Asn Ala Asn Val Thr Asp Ala Ile
130 135 140
Leu Glu Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Tyr Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Ser Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Asp Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro Asn Gly Thr Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Cys Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Cys Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Leu Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Cys Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Cys Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 88
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPA-M2-CO
<400> 88
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Ala Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Glu Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Ala Cys Leu Gly His Tyr Trp Arg Gln
50 55 60
Arg Leu Val Ala Asp Glu Leu Leu Pro Asn Gln Thr Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Gly Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His Thr Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Asn Ala Asn Val Thr Asp Ala Ile
130 135 140
Leu Glu Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Tyr Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Ser Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Asp Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro Asn Gly Thr Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Glu Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Cys Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Cys Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Ala Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Cys Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 89
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPA-M2
<400> 89
cagtccgagc ccgagctgaa gctggagtcc gtcgtcatcg tctcccgcca cggtgtccgc 60
gcccccacca aggccaccca gctgatgcag gacgtcaccc ccgacgcctg gcccacctgg 120
cccgtcaagc tgggtgagct gaccccccgc ggtggtgagc tgatcgccta cctgggtcac 180
tactggcgcc agcgcctggt cgccgacgag ctgctgccca accagacctg cccccagtcc 240
ggtcaggtcg ccatcatcgc cgacgtcgac gagcgcaccc gcaagaccgg tgaggccttc 300
gccgccggtc tggcccccga ctgcgccatc accgtccaca cccaggccga cacctcctcc 360
cccgaccccc tgttcaaccc cctgaagacc ggtgtctgcc agctggacaa cgccaacgtc 420
accgacgcca tcctggagcg cgccggtggt tccatcgccg acttcaccgg tcactaccag 480
accgccttcc gcgagctgga gcgcgtcctg aacttctccc agtccaacct gtgcctgaag 540
cgcgagaagc aggacgagtc ctgctccctg acccaggccc tgccctccga gctgaaggtc 600
tccgccgaca acgtctccct gaccggtgcc gtctccctgg cctccatgct gaccgagatc 660
ttcctgctgc agcaggccca gggtatgccc gagcccggtt ggggtcgcat caccgactcc 720
caccagtgga acaccctgct gtccctgcac aacgcccagt tcgacctgct gcagcgcacc 780
cccgaggtcg cccgctcccg cgccaccccc ctgctggacc tgatcaagac cgccctgacc 840
cccaacggta cccagaagca ggcctacggt gtcaccctgc ccacctccgt cctgttcatc 900
gccggtcacg acaccaacct ggccaacctg ggtggtgccc tggagctgaa ctggaccctg 960
cccggtcagc ccgacaacac cccccccggt ggtgagctgg tcttcgagcg ctggcgccgc 1020
ctgtccgaca actcccagtg gatccaggtc tccctggtct tccagaccct gcagcagatg 1080
cgcgacaaga cccccctgtc cctgaacacc ccccccggtg aggtcaagct gaccctggcc 1140
ggttgcgagg agcgcaacgc ccagggtatg tgctccctgg ccggtttcac ccagatcgtc 1200
aacgaggccc gcatccccgc ctgctccctg taa 1233
<210> 90
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPA-M2-B
<400> 90
cagtccgagc ccgagctgaa gctggagtcc gtcgtcatcg tctcccgcca cggtgtccgc 60
gcccccacca aggccaccca gctgatgcag gacgtcaccc ccgacgcctg gcccacctgg 120
cccgtcaagc tgggtgagct gaccccccgc ggtggtgagc tgatctgcta cctgggtcac 180
tactggcgcc agcgcctggt cgccgacgag ctgctgccca accagacctg cccccagtcc 240
ggtcaggtcg ccatcatcgc cgacgtcgac gagcgcaccc gcaagaccgg tgaggccttc 300
gccgcctgcc tggcccccga ctgcgccatc accgtccaca cccaggccga cacctcctcc 360
cccgaccccc tgttcaaccc cctgaagacc ggtgtctgcc agctggacaa cgccaacgtc 420
accgacgcca tcctggagcg cgccggtggt tccatcgccg acttcaccgg tcactaccag 480
accgccttcc gcgagctgga gcgcgtcctg aacttctccc agtccaacct gtgcctgaag 540
cgcgagaagc aggacgagtc ctgctccctg acccaggccc tgccctccga gctgaaggtc 600
tccgccgaca acgtctccct gaccggtgcc gtctccctgg cctccatgct gaccgagatc 660
ttcctgctgc agcaggccca gggtatgccc gagcccggtt ggggtcgcat caccgactcc 720
caccagtgga acaccctgct gtccctgcac aacgcccagt tcgacctgct gcagcgcacc 780
cccgaggtcg cccgctcccg cgccaccccc ctgctggacc tgatcaagac cgccctgacc 840
cccaacggta cccagaagca ggcctacggt gtcaccctgc ccacctccgt cctgttcatc 900
gccggtcacg acaccaacct ggccaacctg ggtggtgccc tggagctgaa ctggaccctg 960
cccggtcagc ccgacaacac cccccccggt ggtgagctgg tcttcgagcg ctggcgccgc 1020
ctgtccgaca actcccagtg gatccaggtc tccctggtct tccagaccct gcagcagatg 1080
cgcgacaaga cccccctgtc cctgaacacc ccccccggtg aggtcaagct gaccctggcc 1140
ggttgcgagg agcgcaacgc ccagggtatg tgctccctgg ccggtttcac ccagatcgtc 1200
aacgaggccc gcatccccgc ctgctccctg taa 1233
<210> 91
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> AAPA-M2-C
<400> 91
cagtccgagc ccgagctgaa gctggagtcc gtcgtcatcg tctcccgcca cggtgtccgc 60
gcccccacca aggccaccca gctgatgcag gacgtcaccc ccgacgcctg gcccacctgg 120
cccgtcaagc tgggtgagct gaccccccgc ggtggtgagc tgatcgcctg cctgggtcac 180
tactggcgcc agcgcctggt cgccgacgag ctgctgccca accagacctg cccccagtcc 240
ggtcaggtcg ccatcatcgc cgacgtcgac gagcgcaccc gcaagaccgg tgaggccttc 300
gccgccggtc tggcccccga ctgcgccatc accgtccaca cccaggccga cacctcctcc 360
cccgaccccc tgttcaaccc cctgaagacc ggtgtctgcc agctggacaa cgccaacgtc 420
accgacgcca tcctggagcg cgccggtggt tccatcgccg acttcaccgg tcactaccag 480
accgccttcc gcgagctgga gcgcgtcctg aacttctccc agtccaacct gtgcctgaag 540
cgcgagaagc aggacgagtc ctgctccctg acccaggccc tgccctccga gctgaaggtc 600
tccgccgaca acgtctccct gaccggtgcc gtctccctgg cctccatgct gaccgagatc 660
ttcctgctgc agcaggccca gggtatgccc gagcccggtt ggggtcgcat caccgactcc 720
caccagtgga acaccctgct gtccctgcac aacgcccagt tcgacctgct gcagcgcacc 780
cccgaggtcg cccgctcccg cgccaccccc ctgctggacc tgatcaagac cgccctgacc 840
cccaacggta cccagaagca ggcctacggt gtcaccctgc ccacctccgt cctgttcatc 900
gccggtcacg acaccaacct ggccaacctg ggtggtgccc tggagctgaa ctggaccctg 960
cccggtcagc ccgacaacac cccccccggt ggtgagctgg tcttcgagcg ctggcgccgc 1020
ctgtccgaca actcccagtg gatccaggtc tccctggtct tccagaccct gcagcagatg 1080
cgcgacaaga ccccctgctc cctgaacacc ccccccggtg aggtcaagct gaccctggcc 1140
ggttgcgagg agcgcaacgc ccagggtatg tgctccctgg ccggtttcac ccagatcgtc 1200
aacgaggccc gcatccccgc ctgctccctg taa 1233
<210> 92
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> AAPA-M2-D
<400> 92
cagtccgagc ccgagctgaa gctggagtcc gtcgtcatcg tctcccgcca cggtgtccgc 60
gcccccacca aggccaccca gctgatgcag gacgtcaccc ccgacgcctg gcccacctgg 120
cccgtcaagc tgggtgagct gaccccccgc ggtggtgagc tgatcgccta cctgggtcac 180
tgctggcgcc agcgcctggt cgccgacgag ctgctgccca accagacctg cccccagtcc 240
ggtcaggtcg ccatcatcgc cgacgtcgac gagcgcaccc gcaagaccgg tgaggccttc 300
gccgccggtc tggcccccga ctgcgccatc accgtccaca cccaggccga cacctcctcc 360
cccgaccccc tgttcaaccc cctgaagacc ggtgtctgcc agctggacaa cgccaacgtc 420
accgacgcca tcctggagcg cgccggtggt tccatcgccg acttcaccgg tcactaccag 480
accgccttcc gcgagctgga gcgcgtcctg aacttctccc agtccaacct gtgcctgaag 540
cgcgagaagc aggacgagtc ctgctccctg acccaggccc tgccctccga gctgaaggtc 600
tccgccgaca acgtctccct gaccggtgcc gtctccctgg cctccatgct gaccgagatc 660
ttcctgctgc agcaggccca gggtatgccc gagcccggtt ggggtcgcat caccgactcc 720
caccagtgga acaccctgct gtccctgcac aacgcccagt tcgacctgct gcagcgcacc 780
cccgaggtcg cccgctcccg cgccaccccc ctgctggacc tgatcaagac cgccctgacc 840
cccaacggta cccagaagca ggcctacggt gtcaccctgc ccacctccgt cctgttcatc 900
gccggtcacg acaccaacct ggccaacctg ggtggtgccc tggagctgaa ctggaccctg 960
cccggtcagc ccgacaacac cccccccggt ggtgagctgg tcttcgagcg ctggcgccgc 1020
ctgtccgaca actcccagtg gatccaggtc tccctggtct tccagaccct gcagcagatg 1080
cgcgacaaga ccccctgctc cctgaacacc ccccccggtg aggtcaagct gaccctggcc 1140
ggttgcgagg agcgcaacgc ccagggtatg tgctccctgg ccggtttcac ccagatcgtc 1200
aacgaggccc gcatccccgc ctgctccctg taa 1233
<210> 93
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPA-M2-M
<400> 93
cagtccgagc ccgagctgaa gctggagtcc gtcgtcatcg tctcccgcca cggtgtccgc 60
gcccccacca aggccaccca gctgatgcag gacgtcaccc ccgacgcctg gcccacctgg 120
cccgtcaagc tgggtgagct gaccccccgc ggtggtgagc tgatcgccta cctgggtcac 180
tactggcgcc agcgcctggt cgccgacgag ctgctgccca accagacctg cccccagtcc 240
ggtcaggtcg ccatcatcgc cgacgtcgac gagcgcaccc gcaagaccgg tgaggccttc 300
gccgccggtc tggcccccga ctgcgccatc accgtccaca cccaggccga cacctcctcc 360
cccgaccccc tgttcaaccc cctgaagacc ggtgtctgcc agctggacaa cgccaacgtc 420
accgacgcca tcctggagcg cgccggtggt tccatcgccg acttcaccgg tcactaccag 480
accgccttcc gcgagctgga gcgcgtcctg aacttctccc agtccaacct gtgcctgaag 540
cgcgagaagc aggacgagtc ctgctccctg acccaggccc tgccctccga gctgaaggtc 600
tccgccgaca acgtctccct gaccggtgcc gtctccctgg cctccatgct gaccgagatc 660
ttcctgctgc agcaggccca gggtatgccc gagcccggtt ggggtcgcat caccgactcc 720
caccagtgga acaccctgct gtccctgcac aacgcccagt tcgacctgct gcagcgcacc 780
cccgaggtcg cccgctcccg cgccaccccc ctgctggacc tgatcaagac cgccctgacc 840
cccaacggta cccagaagca ggcctacggt gtcaccctgc ccacctccgt cctgttcatc 900
gccggtcacg acaccaacct ggccaacctg ggtggtgccc tgtgcctgaa ctggaccctg 960
cccggtcagc ccgacaacac cccccccggt ggtgagctgg tcttcgagcg ctggcgccgc 1020
ctgtccgaca actcccagtg gatccaggtc tccctggtct tccagaccct gcagcagatg 1080
cgcgacaaga cccccctgtc cctgaacacc ccccccggtg aggtcaagct gaccctgtgc 1140
ggttgcgagg agcgcaacgc ccagggtatg tgctccctgg ccggtttcac ccagatcgtc 1200
aacgaggccc gcatccccgc ctgctccctg taa 1233
<210> 94
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPA-M2-O
<400> 94
cagtccgagc ccgagctgaa gctggagtcc gtcgtcatcg tctcccgcca cggtgtccgc 60
gcccccacca aggccaccca gctgatgcag gacgtcaccc ccgacgcctg gcccacctgg 120
cccgtcaagc tgggtgagct gaccccccgc ggtggtgagc tgatctgcta cctgggtcac 180
tactggcgcc agcgcctggt cgccgacgag ctgctgccca accagacctg cccccagtcc 240
ggtcaggtcg ccatcatcgc cgacgtcgac gagcgcaccc gcaagaccgg tgaggccttc 300
gccgcctgcc tggcccccga ctgcgccatc accgtccaca cccaggccga cacctcctcc 360
cccgaccccc tgttcaaccc cctgaagacc ggtgtctgcc agctggacaa cgccaacgtc 420
accgacgcca tcctggagcg cgccggtggt tccatcgccg acttcaccgg tcactaccag 480
accgccttcc gcgagctgga gcgcgtcctg aacttctccc agtccaacct gtgcctgaag 540
cgcgagaagc aggacgagtc ctgctccctg acccaggccc tgccctccga gctgaaggtc 600
tccgccgaca acgtctccct gaccggtgcc gtctccctgg cctccatgct gaccgagatc 660
ttcctgctgc agcaggccca gggtatgccc gagcccggtt ggggtcgcat caccgactcc 720
caccagtgga acaccctgct gtccctgcac aacgcccagt tcgacctgct gcagcgcacc 780
cccgaggtcg cccgctcccg cgccaccccc ctgctggacc tgatcaagac cgccctgacc 840
cccaacggta cccagaagca ggcctacggt gtcaccctgc ccacctccgt cctgttcatc 900
gccggtcacg acaccaacct ggccaacctg ggtggtgccc tggagctgaa ctggaccctg 960
cccggtcagc ccgacaacac cccccccggt ggtgagctgg tcttcgagcg ctggcgccgc 1020
ctgtccgaca actcccagtg gatccaggtc tccctggtct tccagaccct gcagcagatg 1080
cgcgacaaga cccccctgtc cctgaacacc ccccccggtg aggtcaagct gaccctggcc 1140
ggttgcgagg agcgcaacgc ccagggtatg tgctccctgg ccggtttcac ccagatcgtc 1200
aacgaggccc gcatccccgc ctgctccctg taa 1233
<210> 95
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> AAPA-M2-BO
<400> 95
cagtccgagc ccgagctgaa gctggagtcc gtcgtcatcg tctcccgcca cggtgtccgc 60
gcccccacca aggccaccca gctgatgcag gacgtcaccc ccgacgcctg gcccacctgg 120
cccgtcaagc tgggtgagct gaccccccgc ggtggtgagc tgatctgcta cctgggtcac 180
tactggcgcc agcgcctggt cgccgacgag ctgctgccca accagacctg cccccagtcc 240
ggtcaggtcg ccatcatcgc cgacgtcgac gagcgcaccc gcaagaccgg tgaggccttc 300
gccgcctgcc tggcccccga ctgcgccatc accgtccaca cccaggccga cacctcctcc 360
cccgaccccc tgttcaaccc cctgaagacc ggtgtctgcc agctggacaa cgccaacgtc 420
accgacgcca tcctggagcg cgccggtggt tccatcgccg acttcaccgg tcactaccag 480
accgccttcc gcgagctgga gcgcgtcctg aacttctccc agtccaacct gtgcctgaag 540
cgcgagaagc aggacgagtc ctgctccctg acccaggccc tgccctccga gctgaaggtc 600
tccgccgaca acgtctccct gaccggtgcc gtctccctgg cctccatgct gaccgagatc 660
ttcctgctgc agcaggccca gggtatgccc gagcccggtt ggggtcgcat caccgactcc 720
caccagtgga acaccctgct gtccctgcac aacgcccagt tcgacctgct gcagcgcacc 780
cccgaggtcg cccgctcccg cgccaccccc ctgctggacc tgatcaagac cgccctgacc 840
cccaacggta cccagaagca ggcctacggt gtcaccctgc ccacctccgt cctgttcatc 900
gccggtcacg acaccaacct ggccaacctg ggtggtgccc tggagctgaa ctggaccctg 960
cccggtcagc ccgacaacac cccccccggt ggtgagctgg tcttcgagcg ctggcgccgc 1020
ctgtccgaca actcctgctg gatccaggtc tccctggtct tccagaccct gcagcagatg 1080
cgcgacaaga cccccctgtc cctgaacacc ccccccggtg aggtcaagct gaccctggcc 1140
ggttgcgagg agcgcaacgc ccagggtatg tgctcctgcg ccggtttcac ccagatcgtc 1200
aacgaggccc gcatccccgc ctgctccctg taa 1233
<210> 96
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPA-M2-DO
<400> 96
cagtccgagc ccgagctgaa gctggagtcc gtcgtcatcg tctcccgcca cggtgtccgc 60
gcccccacca aggccaccca gctgatgcag gacgtcaccc ccgacgcctg gcccacctgg 120
cccgtcaagc tgggtgagct gaccccccgc ggtggtgagc tgatcgccta cctgggtcac 180
tgctggcgcc agcgcctggt cgccgacgag ctgctgccca accagacctg cccccagtcc 240
ggtcaggtcg ccatcatcgc cgacgtcgac gagcgcaccc gcaagaccgg tgaggccttc 300
gccgccggtc tggcccccga ctgcgccatc accgtccaca cccaggccga cacctcctcc 360
cccgaccccc tgttcaaccc cctgaagacc ggtgtctgcc agctggacaa cgccaacgtc 420
accgacgcca tcctggagcg cgccggtggt tccatcgccg acttcaccgg tcactaccag 480
accgccttcc gcgagctgga gcgcgtcctg aacttctccc agtccaacct gtgcctgaag 540
cgcgagaagc aggacgagtc ctgctccctg acccaggccc tgccctccga gctgaaggtc 600
tccgccgaca acgtctccct gaccggtgcc gtctccctgg cctccatgct gaccgagatc 660
ttcctgctgc agcaggccca gggtatgccc gagcccggtt ggggtcgcat caccgactcc 720
caccagtgga acaccctgct gtccctgcac aacgcccagt tcgacctgct gcagcgcacc 780
cccgaggtcg cccgctcccg cgccaccccc ctgctggacc tgatcaagac cgccctgacc 840
cccaacggta cccagaagca ggcctacggt gtcaccctgc ccacctccgt cctgttcatc 900
gccggtcacg acaccaacct ggccaacctg ggtggtgccc tggagctgaa ctggaccctg 960
cccggtcagc ccgacaacac cccccccggt ggtgagctgg tcttcgagcg ctggcgccgc 1020
ctgtccgaca actcctgctg gatccaggtc tccctggtct tccagaccct gcagcagatg 1080
cgcgacaaga ccccctgctc cctgaacacc ccccccggtg aggtcaagct gaccctggcc 1140
ggttgcgagg agcgcaacgc ccagggtatg tgctcctgcg ccggtttcac ccagatcgtc 1200
aacgaggccc gcatccccgc ctgctccctg taa 1233
<210> 97
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPA-M2-MO
<400> 97
cagtccgagc ccgagctgaa gctggagtcc gtcgtcatcg tctcccgcca cggtgtccgc 60
gcccccacca aggccaccca gctgatgcag gacgtcaccc ccgacgcctg gcccacctgg 120
cccgtcaagc tgggtgagct gaccccccgc ggtggtgagc tgatcgccta cctgggtcac 180
tactggcgcc agcgcctggt cgccgacgag ctgctgccca accagacctg cccccagtcc 240
ggtcaggtcg ccatcatcgc cgacgtcgac gagcgcaccc gcaagaccgg tgaggccttc 300
gccgccggtc tggcccccga ctgcgccatc accgtccaca cccaggccga cacctcctcc 360
cccgaccccc tgttcaaccc cctgaagacc ggtgtctgcc agctggacaa cgccaacgtc 420
accgacgcca tcctggagcg cgccggtggt tccatcgccg acttcaccgg tcactaccag 480
accgccttcc gcgagctgga gcgcgtcctg aacttctccc agtccaacct gtgcctgaag 540
cgcgagaagc aggacgagtc ctgctccctg acccaggccc tgccctccga gctgaaggtc 600
tccgccgaca acgtctccct gaccggtgcc gtctccctgg cctccatgct gaccgagatc 660
ttcctgctgc agcaggccca gggtatgccc gagcccggtt ggggtcgcat caccgactcc 720
caccagtgga acaccctgct gtccctgcac aacgcccagt tcgacctgct gcagcgcacc 780
cccgaggtcg cccgctcccg cgccaccccc ctgctggacc tgatcaagac cgccctgacc 840
cccaacggta cccagaagca ggcctacggt gtcaccctgc ccacctccgt cctgttcatc 900
gccggtcacg acaccaacct ggccaacctg ggtggtgccc tgtgcctgaa ctggaccctg 960
cccggtcagc ccgacaacac cccccccggt ggtgagctgg tcttcgagcg ctggcgccgc 1020
ctgtccgaca actcctgctg gatccaggtc tccctggtct tccagaccct gcagcagatg 1080
cgcgacaaga cccccctgtc cctgaacacc ccccccggtg aggtcaagct gaccctgtgc 1140
ggttgcgagg agcgcaacgc ccagggtatg tgctcctgcg ccggtttcac ccagatcgtc 1200
aacgaggccc gcatccccgc ctgctccctg taa 1233
<210> 98
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> AAPA-M2-CO
<400> 98
cagtccgagc ccgagctgaa gctggagtcc gtcgtcatcg tctcccgcca cggtgtccgc 60
gcccccacca aggccaccca gctgatgcag gacgtcaccc ccgacgcctg gcccacctgg 120
cccgtcaagc tgggtgagct gaccccccgc ggtggtgagc tgatcgcctg cctgggtcac 180
tactggcgcc agcgcctggt cgccgacgag ctgctgccca accagacctg cccccagtcc 240
ggtcaggtcg ccatcatcgc cgacgtcgac gagcgcaccc gcaagaccgg tgaggccttc 300
gccgccggtc tggcccccga ctgcgccatc accgtccaca cccaggccga cacctcctcc 360
cccgaccccc tgttcaaccc cctgaagacc ggtgtctgcc agctggacaa cgccaacgtc 420
accgacgcca tcctggagcg cgccggtggt tccatcgccg acttcaccgg tcactaccag 480
accgccttcc gcgagctgga gcgcgtcctg aacttctccc agtccaacct gtgcctgaag 540
cgcgagaagc aggacgagtc ctgctccctg acccaggccc tgccctccga gctgaaggtc 600
tccgccgaca acgtctccct gaccggtgcc gtctccctgg cctccatgct gaccgagatc 660
ttcctgctgc agcaggccca gggtatgccc gagcccggtt ggggtcgcat caccgactcc 720
caccagtgga acaccctgct gtccctgcac aacgcccagt tcgacctgct gcagcgcacc 780
cccgaggtcg cccgctcccg cgccaccccc ctgctggacc tgatcaagac cgccctgacc 840
cccaacggta cccagaagca ggcctacggt gtcaccctgc ccacctccgt cctgttcatc 900
gccggtcacg acaccaacct ggccaacctg ggtggtgccc tggagctgaa ctggaccctg 960
cccggtcagc ccgacaacac cccccccggt ggtgagctgg tcttcgagcg ctggcgccgc 1020
ctgtccgaca actcctgctg gatccaggtc tccctggtct tccagaccct gcagcagatg 1080
cgcgacaaga ccccctgctc cctgaacacc ccccccggtg aggtcaagct gaccctggcc 1140
ggttgcgagg agcgcaacgc ccagggtatg tgctcctgcg ccggtttcac ccagatcgtc 1200
aacgaggccc gcatccccgc ctgctccctg taa 1233
<210> 99
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPA-M3
<400> 99
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Phe Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Glu Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Ala Tyr Leu Gly His Tyr Trp Arg Gln
50 55 60
Arg Leu Val Ala Asp Glu Leu Leu Pro Asn Gln Thr Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Gly Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His His Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Val Ala Asn Val Thr Arg Ala Ile
130 135 140
Leu Glu Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Tyr Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Ser Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Asp Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro Asn Gly Thr Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Glu Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Gln Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Leu Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Ala Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Leu Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 100
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPA-M3-B
<400> 100
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Phe Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Glu Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Cys Tyr Leu Gly His Tyr Trp Arg Gln
50 55 60
Arg Leu Val Ala Asp Glu Leu Leu Pro Asn Gln Thr Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Cys Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His His Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Val Ala Asn Val Thr Arg Ala Ile
130 135 140
Leu Glu Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Tyr Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Ser Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Asp Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro Asn Gly Thr Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Glu Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Gln Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Leu Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Ala Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Leu Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 101
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPA-M3-D
<400> 101
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Phe Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Glu Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Ala Tyr Leu Gly His Cys Trp Arg Gln
50 55 60
Arg Leu Val Ala Asp Glu Leu Leu Pro Asn Gln Thr Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Gly Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His His Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Val Ala Asn Val Thr Arg Ala Ile
130 135 140
Leu Glu Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Tyr Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Ser Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Asp Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro Asn Gly Thr Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Glu Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Gln Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Cys Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Ala Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Leu Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 102
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPA-M3-M
<400> 102
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Phe Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Glu Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Ala Tyr Leu Gly His Tyr Trp Arg Gln
50 55 60
Arg Leu Val Ala Asp Glu Leu Leu Pro Asn Gln Thr Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Gly Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His His Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Val Ala Asn Val Thr Arg Ala Ile
130 135 140
Leu Glu Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Tyr Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Ser Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Asp Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro Asn Gly Thr Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Cys Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Gln Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Leu Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Cys Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Leu Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 103
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPA-M3-O
<400> 103
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Phe Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Glu Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Ala Tyr Leu Gly His Tyr Trp Arg Gln
50 55 60
Arg Leu Val Ala Asp Glu Leu Leu Pro Asn Gln Thr Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Gly Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His His Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Val Ala Asn Val Thr Arg Ala Ile
130 135 140
Leu Glu Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Tyr Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Ser Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Asp Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro Asn Gly Thr Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Glu Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Cys Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Leu Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Ala Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Cys Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 104
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPA-M3-C
<400> 104
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Phe Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Glu Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Ala Cys Leu Gly His Tyr Trp Arg Gln
50 55 60
Arg Leu Val Ala Asp Glu Leu Leu Pro Asn Gln Thr Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Gly Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His His Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Val Ala Asn Val Thr Arg Ala Ile
130 135 140
Leu Glu Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Tyr Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Ser Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Asp Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro Asn Gly Thr Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Glu Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Gln Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Cys Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Ala Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Leu Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 105
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPA-M3-BO
<400> 105
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Phe Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Glu Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Cys Tyr Leu Gly His Tyr Trp Arg Gln
50 55 60
Arg Leu Val Ala Asp Glu Leu Leu Pro Asn Gln Thr Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Cys Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His His Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Val Ala Asn Val Thr Arg Ala Ile
130 135 140
Leu Glu Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Tyr Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Ser Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Asp Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro Asn Gly Thr Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Glu Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Cys Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Leu Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Ala Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Cys Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 106
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPA-M3-DO
<400> 106
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Phe Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Glu Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Ala Tyr Leu Gly His Cys Trp Arg Gln
50 55 60
Arg Leu Val Ala Asp Glu Leu Leu Pro Asn Gln Thr Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Gly Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His His Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Val Ala Asn Val Thr Arg Ala Ile
130 135 140
Leu Glu Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Tyr Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Ser Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Asp Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro Asn Gly Thr Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Glu Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Cys Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Cys Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Ala Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Cys Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 107
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPA-M3-MO
<400> 107
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Phe Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Glu Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Ala Tyr Leu Gly His Tyr Trp Arg Gln
50 55 60
Arg Leu Val Ala Asp Glu Leu Leu Pro Asn Gln Thr Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Gly Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His His Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Val Ala Asn Val Thr Arg Ala Ile
130 135 140
Leu Glu Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Tyr Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Ser Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Asp Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro Asn Gly Thr Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Cys Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Cys Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Leu Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Cys Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Cys Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 108
<211> 410
<212> PRT
<213> Artificial Sequence
<220>
<223> APPA-M3-CO
<400> 108
Gln Ser Glu Pro Glu Leu Lys Leu Glu Ser Val Val Ile Val Ser Arg
1 5 10 15
His Gly Val Arg Ala Pro Thr Lys Phe Thr Gln Leu Met Gln Asp Val
20 25 30
Thr Pro Asp Ala Trp Pro Thr Trp Pro Val Lys Leu Gly Glu Leu Thr
35 40 45
Pro Arg Gly Gly Glu Leu Ile Ala Cys Leu Gly His Tyr Trp Arg Gln
50 55 60
Arg Leu Val Ala Asp Glu Leu Leu Pro Asn Gln Thr Cys Pro Gln Ser
65 70 75 80
Gly Gln Val Ala Ile Ile Ala Asp Val Asp Glu Arg Thr Arg Lys Thr
85 90 95
Gly Glu Ala Phe Ala Ala Gly Leu Ala Pro Asp Cys Ala Ile Thr Val
100 105 110
His His Gln Ala Asp Thr Ser Ser Pro Asp Pro Leu Phe Asn Pro Leu
115 120 125
Lys Thr Gly Val Cys Gln Leu Asp Val Ala Asn Val Thr Arg Ala Ile
130 135 140
Leu Glu Arg Ala Gly Gly Ser Ile Ala Asp Phe Thr Gly His Tyr Gln
145 150 155 160
Thr Ala Phe Arg Glu Leu Glu Arg Val Leu Asn Phe Ser Gln Ser Asn
165 170 175
Leu Cys Leu Lys Arg Glu Lys Gln Asp Glu Ser Cys Ser Leu Thr Gln
180 185 190
Ala Leu Pro Ser Glu Leu Lys Val Ser Ala Asp Asn Val Ser Leu Thr
195 200 205
Gly Ala Val Ser Leu Ala Ser Met Leu Thr Glu Ile Phe Leu Leu Gln
210 215 220
Gln Ala Gln Gly Met Pro Glu Pro Gly Trp Gly Arg Ile Thr Asp Ser
225 230 235 240
His Gln Trp Asn Thr Leu Leu Ser Leu His Asn Ala Gln Phe Asp Leu
245 250 255
Leu Gln Arg Thr Pro Glu Val Ala Arg Ser Arg Ala Thr Pro Leu Leu
260 265 270
Asp Leu Ile Lys Thr Ala Leu Thr Pro Asn Gly Thr Gln Lys Gln Ala
275 280 285
Tyr Gly Val Thr Leu Pro Thr Ser Val Leu Phe Ile Ala Gly His Asp
290 295 300
Thr Asn Leu Ala Asn Leu Gly Gly Ala Leu Glu Leu Asn Trp Thr Leu
305 310 315 320
Pro Gly Gln Pro Asp Asn Thr Pro Pro Gly Gly Glu Leu Val Phe Glu
325 330 335
Arg Trp Arg Arg Leu Ser Asp Asn Ser Cys Trp Ile Gln Val Ser Leu
340 345 350
Val Phe Gln Thr Leu Gln Gln Met Arg Asp Lys Thr Pro Cys Ser Leu
355 360 365
Asn Thr Pro Pro Gly Glu Val Lys Leu Thr Leu Ala Gly Cys Glu Glu
370 375 380
Arg Asn Ala Gln Gly Met Cys Ser Cys Ala Gly Phe Thr Gln Ile Val
385 390 395 400
Asn Glu Ala Arg Ile Pro Ala Cys Ser Leu
405 410
<210> 109
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPA-M3
<400> 109
cagtccgagc ccgagctcaa gctcgagtcc gtcgtcatcg tctcccgcca cggtgtccgc 60
gcccccacca agttcaccca gctcatgcag gacgtcaccc ccgacgcctg gcccacctgg 120
cccgtcaagc tcggtgagct caccccccgc ggtggtgagc tcatcgccta cctcggtcac 180
tactggcgcc agcgcctcgt cgccgacgag ctcctcccca accagacctg cccccagtcc 240
ggtcaggtcg ccatcatcgc cgacgtcgac gagcgcaccc gcaagaccgg tgaggccttc 300
gccgccggtc tcgcccccga ctgcgccatc accgtccacc accaggccga cacctcctcc 360
cccgaccccc tcttcaaccc cctcaagacc ggtgtctgcc agctcgacgt cgccaacgtc 420
acccgcgcca tcctcgagcg cgccggtggt tccatcgccg acttcaccgg tcactaccag 480
accgccttcc gcgagctcga gcgcgtcctc aacttctccc agtccaacct ctgcctcaag 540
cgcgagaagc aggacgagtc ctgctccctc acccaggccc tcccctccga gctcaaggtc 600
tccgccgaca acgtctccct caccggtgcc gtctccctcg cctccatgct caccgagatc 660
ttcctcctcc agcaggccca gggtatgccc gagcccggtt ggggtcgcat caccgactcc 720
caccagtgga acaccctcct ctccctccac aacgcccagt tcgacctcct ccagcgcacc 780
cccgaggtcg cccgctcccg cgccaccccc ctcctcgacc tcatcaagac cgccctcacc 840
cccaacggta cccagaagca ggcctacggt gtcaccctcc ccacctccgt cctcttcatc 900
gccggtcacg acaccaacct cgccaacctc ggtggtgccc tcgagctcaa ctggaccctc 960
cccggtcagc ccgacaacac cccccccggt ggtgagctcg tcttcgagcg ctggcgccgc 1020
ctctccgaca actcccagtg gatccaggtc tccctcgtct tccagaccct ccagcagatg 1080
cgcgacaaga cccccctctc cctcaacacc ccccccggtg aggtcaagct caccctcgcc 1140
ggttgcgagg agcgcaacgc ccagggtatg tgctccctcg ccggtttcac ccagatcgtc 1200
aacgaggccc gcatccccgc ctgctccctc taa 1233
<210> 110
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPA-M3-B
<400> 110
cagtccgagc ccgagctcaa gctcgagtcc gtcgtcatcg tctcccgcca cggtgtccgc 60
gcccccacca agttcaccca gctcatgcag gacgtcaccc ccgacgcctg gcccacctgg 120
cccgtcaagc tcggtgagct caccccccgc ggtggtgagc tcatctgcta cctcggtcac 180
tactggcgcc agcgcctcgt cgccgacgag ctcctcccca accagacctg cccccagtcc 240
ggtcaggtcg ccatcatcgc cgacgtcgac gagcgcaccc gcaagaccgg tgaggccttc 300
gccgcctgcc tcgcccccga ctgcgccatc accgtccacc accaggccga cacctcctcc 360
cccgaccccc tcttcaaccc cctcaagacc ggtgtctgcc agctcgacgt cgccaacgtc 420
acccgcgcca tcctcgagcg cgccggtggt tccatcgccg acttcaccgg tcactaccag 480
accgccttcc gcgagctcga gcgcgtcctc aacttctccc agtccaacct ctgcctcaag 540
cgcgagaagc aggacgagtc ctgctccctc acccaggccc tcccctccga gctcaaggtc 600
tccgccgaca acgtctccct caccggtgcc gtctccctcg cctccatgct caccgagatc 660
ttcctcctcc agcaggccca gggtatgccc gagcccggtt ggggtcgcat caccgactcc 720
caccagtgga acaccctcct ctccctccac aacgcccagt tcgacctcct ccagcgcacc 780
cccgaggtcg cccgctcccg cgccaccccc ctcctcgacc tcatcaagac cgccctcacc 840
cccaacggta cccagaagca ggcctacggt gtcaccctcc ccacctccgt cctcttcatc 900
gccggtcacg acaccaacct cgccaacctc ggtggtgccc tcgagctcaa ctggaccctc 960
cccggtcagc ccgacaacac cccccccggt ggtgagctcg tcttcgagcg ctggcgccgc 1020
ctctccgaca actcccagtg gatccaggtc tccctcgtct tccagaccct ccagcagatg 1080
cgcgacaaga cccccctctc cctcaacacc ccccccggtg aggtcaagct caccctcgcc 1140
ggttgcgagg agcgcaacgc ccagggtatg tgctccctcg ccggtttcac ccagatcgtc 1200
aacgaggccc gcatccccgc ctgctccctc taa 1233
<210> 111
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPA-M3-D
<400> 111
cagtccgagc ccgagctcaa gctcgagtcc gtcgtcatcg tctcccgcca cggtgtccgc 60
gcccccacca agttcaccca gctcatgcag gacgtcaccc ccgacgcctg gcccacctgg 120
cccgtcaagc tcggtgagct caccccccgc ggtggtgagc tcatcgccta cctcggtcac 180
tgctggcgcc agcgcctcgt cgccgacgag ctcctcccca accagacctg cccccagtcc 240
ggtcaggtcg ccatcatcgc cgacgtcgac gagcgcaccc gcaagaccgg tgaggccttc 300
gccgccggtc tcgcccccga ctgcgccatc accgtccacc accaggccga cacctcctcc 360
cccgaccccc tcttcaaccc cctcaagacc ggtgtctgcc agctcgacgt cgccaacgtc 420
acccgcgcca tcctcgagcg cgccggtggt tccatcgccg acttcaccgg tcactaccag 480
accgccttcc gcgagctcga gcgcgtcctc aacttctccc agtccaacct ctgcctcaag 540
cgcgagaagc aggacgagtc ctgctccctc acccaggccc tcccctccga gctcaaggtc 600
tccgccgaca acgtctccct caccggtgcc gtctccctcg cctccatgct caccgagatc 660
ttcctcctcc agcaggccca gggtatgccc gagcccggtt ggggtcgcat caccgactcc 720
caccagtgga acaccctcct ctccctccac aacgcccagt tcgacctcct ccagcgcacc 780
cccgaggtcg cccgctcccg cgccaccccc ctcctcgacc tcatcaagac cgccctcacc 840
cccaacggta cccagaagca ggcctacggt gtcaccctcc ccacctccgt cctcttcatc 900
gccggtcacg acaccaacct cgccaacctc ggtggtgccc tcgagctcaa ctggaccctc 960
cccggtcagc ccgacaacac cccccccggt ggtgagctcg tcttcgagcg ctggcgccgc 1020
ctctccgaca actcccagtg gatccaggtc tccctcgtct tccagaccct ccagcagatg 1080
cgcgacaaga ccccctgctc cctcaacacc ccccccggtg aggtcaagct caccctcgcc 1140
ggttgcgagg agcgcaacgc ccagggtatg tgctccctcg ccggtttcac ccagatcgtc 1200
aacgaggccc gcatccccgc ctgctccctc taa 1233
<210> 112
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPA-M3-M
<400> 112
cagtccgagc ccgagctcaa gctcgagtcc gtcgtcatcg tctcccgcca cggtgtccgc 60
gcccccacca agttcaccca gctcatgcag gacgtcaccc ccgacgcctg gcccacctgg 120
cccgtcaagc tcggtgagct caccccccgc ggtggtgagc tcatcgccta cctcggtcac 180
tactggcgcc agcgcctcgt cgccgacgag ctcctcccca accagacctg cccccagtcc 240
ggtcaggtcg ccatcatcgc cgacgtcgac gagcgcaccc gcaagaccgg tgaggccttc 300
gccgccggtc tcgcccccga ctgcgccatc accgtccacc accaggccga cacctcctcc 360
cccgaccccc tcttcaaccc cctcaagacc ggtgtctgcc agctcgacgt cgccaacgtc 420
acccgcgcca tcctcgagcg cgccggtggt tccatcgccg acttcaccgg tcactaccag 480
accgccttcc gcgagctcga gcgcgtcctc aacttctccc agtccaacct ctgcctcaag 540
cgcgagaagc aggacgagtc ctgctccctc acccaggccc tcccctccga gctcaaggtc 600
tccgccgaca acgtctccct caccggtgcc gtctccctcg cctccatgct caccgagatc 660
ttcctcctcc agcaggccca gggtatgccc gagcccggtt ggggtcgcat caccgactcc 720
caccagtgga acaccctcct ctccctccac aacgcccagt tcgacctcct ccagcgcacc 780
cccgaggtcg cccgctcccg cgccaccccc ctcctcgacc tcatcaagac cgccctcacc 840
cccaacggta cccagaagca ggcctacggt gtcaccctcc ccacctccgt cctcttcatc 900
gccggtcacg acaccaacct cgccaacctc ggtggtgccc tctgcctcaa ctggaccctc 960
cccggtcagc ccgacaacac cccccccggt ggtgagctcg tcttcgagcg ctggcgccgc 1020
ctctccgaca actcccagtg gatccaggtc tccctcgtct tccagaccct ccagcagatg 1080
cgcgacaaga cccccctctc cctcaacacc ccccccggtg aggtcaagct caccctctgc 1140
ggttgcgagg agcgcaacgc ccagggtatg tgctccctcg ccggtttcac ccagatcgtc 1200
aacgaggccc gcatccccgc ctgctccctc taa 1233
<210> 113
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPA-M3-O
<400> 113
cagtccgagc ccgagctcaa gctcgagtcc gtcgtcatcg tctcccgcca cggtgtccgc 60
gcccccacca agttcaccca gctcatgcag gacgtcaccc ccgacgcctg gcccacctgg 120
cccgtcaagc tcggtgagct caccccccgc ggtggtgagc tcatcgccta cctcggtcac 180
tactggcgcc agcgcctcgt cgccgacgag ctcctcccca accagacctg cccccagtcc 240
ggtcaggtcg ccatcatcgc cgacgtcgac gagcgcaccc gcaagaccgg tgaggccttc 300
gccgccggtc tcgcccccga ctgcgccatc accgtccacc accaggccga cacctcctcc 360
cccgaccccc tcttcaaccc cctcaagacc ggtgtctgcc agctcgacgt cgccaacgtc 420
acccgcgcca tcctcgagcg cgccggtggt tccatcgccg acttcaccgg tcactaccag 480
accgccttcc gcgagctcga gcgcgtcctc aacttctccc agtccaacct ctgcctcaag 540
cgcgagaagc aggacgagtc ctgctccctc acccaggccc tcccctccga gctcaaggtc 600
tccgccgaca acgtctccct caccggtgcc gtctccctcg cctccatgct caccgagatc 660
ttcctcctcc agcaggccca gggtatgccc gagcccggtt ggggtcgcat caccgactcc 720
caccagtgga acaccctcct ctccctccac aacgcccagt tcgacctcct ccagcgcacc 780
cccgaggtcg cccgctcccg cgccaccccc ctcctcgacc tcatcaagac cgccctcacc 840
cccaacggta cccagaagca ggcctacggt gtcaccctcc ccacctccgt cctcttcatc 900
gccggtcacg acaccaacct cgccaacctc ggtggtgccc tcgagctcaa ctggaccctc 960
cccggtcagc ccgacaacac cccccccggt ggtgagctcg tcttcgagcg ctggcgccgc 1020
ctctccgaca actcctgctg gatccaggtc tccctcgtct tccagaccct ccagcagatg 1080
cgcgacaaga cccccctctc cctcaacacc ccccccggtg aggtcaagct caccctcgcc 1140
ggttgcgagg agcgcaacgc ccagggtatg tgctcctgcg ccggtttcac ccagatcgtc 1200
aacgaggccc gcatccccgc ctgctccctc taa 1233
<210> 114
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPA-M3-C
<400> 114
cagtccgagc ccgagctcaa gctcgagtcc gtcgtcatcg tctcccgcca cggtgtccgc 60
gcccccacca agttcaccca gctcatgcag gacgtcaccc ccgacgcctg gcccacctgg 120
cccgtcaagc tcggtgagct caccccccgc ggtggtgagc tcatcgcctg cctcggtcac 180
tactggcgcc agcgcctcgt cgccgacgag ctcctcccca accagacctg cccccagtcc 240
ggtcaggtcg ccatcatcgc cgacgtcgac gagcgcaccc gcaagaccgg tgaggccttc 300
gccgccggtc tcgcccccga ctgcgccatc accgtccacc accaggccga cacctcctcc 360
cccgaccccc tcttcaaccc cctcaagacc ggtgtctgcc agctcgacgt cgccaacgtc 420
acccgcgcca tcctcgagcg cgccggtggt tccatcgccg acttcaccgg tcactaccag 480
accgccttcc gcgagctcga gcgcgtcctc aacttctccc agtccaacct ctgcctcaag 540
cgcgagaagc aggacgagtc ctgctccctc acccaggccc tcccctccga gctcaaggtc 600
tccgccgaca acgtctccct caccggtgcc gtctccctcg cctccatgct caccgagatc 660
ttcctcctcc agcaggccca gggtatgccc gagcccggtt ggggtcgcat caccgactcc 720
caccagtgga acaccctcct ctccctccac aacgcccagt tcgacctcct ccagcgcacc 780
cccgaggtcg cccgctcccg cgccaccccc ctcctcgacc tcatcaagac cgccctcacc 840
cccaacggta cccagaagca ggcctacggt gtcaccctcc ccacctccgt cctcttcatc 900
gccggtcacg acaccaacct cgccaacctc ggtggtgccc tcgagctcaa ctggaccctc 960
cccggtcagc ccgacaacac cccccccggt ggtgagctcg tcttcgagcg ctggcgccgc 1020
ctctccgaca actcccagtg gatccaggtc tccctcgtct tccagaccct ccagcagatg 1080
cgcgacaaga ccccctgctc cctcaacacc ccccccggtg aggtcaagct caccctcgcc 1140
ggttgcgagg agcgcaacgc ccagggtatg tgctccctcg ccggtttcac ccagatcgtc 1200
aacgaggccc gcatccccgc ctgctccctc taa 1233
<210> 115
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPA-M3-BO
<400> 115
cagtccgagc ccgagctcaa gctcgagtcc gtcgtcatcg tctcccgcca cggtgtccgc 60
gcccccacca agttcaccca gctcatgcag gacgtcaccc ccgacgcctg gcccacctgg 120
cccgtcaagc tcggtgagct caccccccgc ggtggtgagc tcatctgcta cctcggtcac 180
tactggcgcc agcgcctcgt cgccgacgag ctcctcccca accagacctg cccccagtcc 240
ggtcaggtcg ccatcatcgc cgacgtcgac gagcgcaccc gcaagaccgg tgaggccttc 300
gccgcctgcc tcgcccccga ctgcgccatc accgtccacc accaggccga cacctcctcc 360
cccgaccccc tcttcaaccc cctcaagacc ggtgtctgcc agctcgacgt cgccaacgtc 420
acccgcgcca tcctcgagcg cgccggtggt tccatcgccg acttcaccgg tcactaccag 480
accgccttcc gcgagctcga gcgcgtcctc aacttctccc agtccaacct ctgcctcaag 540
cgcgagaagc aggacgagtc ctgctccctc acccaggccc tcccctccga gctcaaggtc 600
tccgccgaca acgtctccct caccggtgcc gtctccctcg cctccatgct caccgagatc 660
ttcctcctcc agcaggccca gggtatgccc gagcccggtt ggggtcgcat caccgactcc 720
caccagtgga acaccctcct ctccctccac aacgcccagt tcgacctcct ccagcgcacc 780
cccgaggtcg cccgctcccg cgccaccccc ctcctcgacc tcatcaagac cgccctcacc 840
cccaacggta cccagaagca ggcctacggt gtcaccctcc ccacctccgt cctcttcatc 900
gccggtcacg acaccaacct cgccaacctc ggtggtgccc tcgagctcaa ctggaccctc 960
cccggtcagc ccgacaacac cccccccggt ggtgagctcg tcttcgagcg ctggcgccgc 1020
ctctccgaca actcctgctg gatccaggtc tccctcgtct tccagaccct ccagcagatg 1080
cgcgacaaga cccccctctc cctcaacacc ccccccggtg aggtcaagct caccctcgcc 1140
ggttgcgagg agcgcaacgc ccagggtatg tgctcctgcg ccggtttcac ccagatcgtc 1200
aacgaggccc gcatccccgc ctgctccctc taa 1233
<210> 116
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPA-M3-DO
<400> 116
cagtccgagc ccgagctcaa gctcgagtcc gtcgtcatcg tctcccgcca cggtgtccgc 60
gcccccacca agttcaccca gctcatgcag gacgtcaccc ccgacgcctg gcccacctgg 120
cccgtcaagc tcggtgagct caccccccgc ggtggtgagc tcatcgccta cctcggtcac 180
tgctggcgcc agcgcctcgt cgccgacgag ctcctcccca accagacctg cccccagtcc 240
ggtcaggtcg ccatcatcgc cgacgtcgac gagcgcaccc gcaagaccgg tgaggccttc 300
gccgccggtc tcgcccccga ctgcgccatc accgtccacc accaggccga cacctcctcc 360
cccgaccccc tcttcaaccc cctcaagacc ggtgtctgcc agctcgacgt cgccaacgtc 420
acccgcgcca tcctcgagcg cgccggtggt tccatcgccg acttcaccgg tcactaccag 480
accgccttcc gcgagctcga gcgcgtcctc aacttctccc agtccaacct ctgcctcaag 540
cgcgagaagc aggacgagtc ctgctccctc acccaggccc tcccctccga gctcaaggtc 600
tccgccgaca acgtctccct caccggtgcc gtctccctcg cctccatgct caccgagatc 660
ttcctcctcc agcaggccca gggtatgccc gagcccggtt ggggtcgcat caccgactcc 720
caccagtgga acaccctcct ctccctccac aacgcccagt tcgacctcct ccagcgcacc 780
cccgaggtcg cccgctcccg cgccaccccc ctcctcgacc tcatcaagac cgccctcacc 840
cccaacggta cccagaagca ggcctacggt gtcaccctcc ccacctccgt cctcttcatc 900
gccggtcacg acaccaacct cgccaacctc ggtggtgccc tcgagctcaa ctggaccctc 960
cccggtcagc ccgacaacac cccccccggt ggtgagctcg tcttcgagcg ctggcgccgc 1020
ctctccgaca actcctgctg gatccaggtc tccctcgtct tccagaccct ccagcagatg 1080
cgcgacaaga ccccctgctc cctcaacacc ccccccggtg aggtcaagct caccctcgcc 1140
ggttgcgagg agcgcaacgc ccagggtatg tgctcctgcg ccggtttcac ccagatcgtc 1200
aacgaggccc gcatccccgc ctgctccctc taa 1233
<210> 117
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPA-M3-MO
<400> 117
cagtccgagc ccgagctcaa gctcgagtcc gtcgtcatcg tctcccgcca cggtgtccgc 60
gcccccacca agttcaccca gctcatgcag gacgtcaccc ccgacgcctg gcccacctgg 120
cccgtcaagc tcggtgagct caccccccgc ggtggtgagc tcatcgccta cctcggtcac 180
tactggcgcc agcgcctcgt cgccgacgag ctcctcccca accagacctg cccccagtcc 240
ggtcaggtcg ccatcatcgc cgacgtcgac gagcgcaccc gcaagaccgg tgaggccttc 300
gccgccggtc tcgcccccga ctgcgccatc accgtccacc accaggccga cacctcctcc 360
cccgaccccc tcttcaaccc cctcaagacc ggtgtctgcc agctcgacgt cgccaacgtc 420
acccgcgcca tcctcgagcg cgccggtggt tccatcgccg acttcaccgg tcactaccag 480
accgccttcc gcgagctcga gcgcgtcctc aacttctccc agtccaacct ctgcctcaag 540
cgcgagaagc aggacgagtc ctgctccctc acccaggccc tcccctccga gctcaaggtc 600
tccgccgaca acgtctccct caccggtgcc gtctccctcg cctccatgct caccgagatc 660
ttcctcctcc agcaggccca gggtatgccc gagcccggtt ggggtcgcat caccgactcc 720
caccagtgga acaccctcct ctccctccac aacgcccagt tcgacctcct ccagcgcacc 780
cccgaggtcg cccgctcccg cgccaccccc ctcctcgacc tcatcaagac cgccctcacc 840
cccaacggta cccagaagca ggcctacggt gtcaccctcc ccacctccgt cctcttcatc 900
gccggtcacg acaccaacct cgccaacctc ggtggtgccc tctgcctcaa ctggaccctc 960
cccggtcagc ccgacaacac cccccccggt ggtgagctcg tcttcgagcg ctggcgccgc 1020
ctctccgaca actcctgctg gatccaggtc tccctcgtct tccagaccct ccagcagatg 1080
cgcgacaaga cccccctctc cctcaacacc ccccccggtg aggtcaagct caccctctgc 1140
ggttgcgagg agcgcaacgc ccagggtatg tgctcctgcg ccggtttcac ccagatcgtc 1200
aacgaggccc gcatccccgc ctgctccctc taa 1233
<210> 118
<211> 1233
<212> DNA
<213> Artificial Sequence
<220>
<223> APPA-M3-CO
<400> 118
cagtccgagc ccgagctcaa gctcgagtcc gtcgtcatcg tctcccgcca cggtgtccgc 60
gcccccacca agttcaccca gctcatgcag gacgtcaccc ccgacgcctg gcccacctgg 120
cccgtcaagc tcggtgagct caccccccgc ggtggtgagc tcatcgcctg cctcggtcac 180
tactggcgcc agcgcctcgt cgccgacgag ctcctcccca accagacctg cccccagtcc 240
ggtcaggtcg ccatcatcgc cgacgtcgac gagcgcaccc gcaagaccgg tgaggccttc 300
gccgccggtc tcgcccccga ctgcgccatc accgtccacc accaggccga cacctcctcc 360
cccgaccccc tcttcaaccc cctcaagacc ggtgtctgcc agctcgacgt cgccaacgtc 420
acccgcgcca tcctcgagcg cgccggtggt tccatcgccg acttcaccgg tcactaccag 480
accgccttcc gcgagctcga gcgcgtcctc aacttctccc agtccaacct ctgcctcaag 540
cgcgagaagc aggacgagtc ctgctccctc acccaggccc tcccctccga gctcaaggtc 600
tccgccgaca acgtctccct caccggtgcc gtctccctcg cctccatgct caccgagatc 660
ttcctcctcc agcaggccca gggtatgccc gagcccggtt ggggtcgcat caccgactcc 720
caccagtgga acaccctcct ctccctccac aacgcccagt tcgacctcct ccagcgcacc 780
cccgaggtcg cccgctcccg cgccaccccc ctcctcgacc tcatcaagac cgccctcacc 840
cccaacggta cccagaagca ggcctacggt gtcaccctcc ccacctccgt cctcttcatc 900
gccggtcacg acaccaacct cgccaacctc ggtggtgccc tcgagctcaa ctggaccctc 960
cccggtcagc ccgacaacac cccccccggt ggtgagctcg tcttcgagcg ctggcgccgc 1020
ctctccgaca actcctgctg gatccaggtc tccctcgtct tccagaccct ccagcagatg 1080
cgcgacaaga ccccctgctc cctcaacacc ccccccggtg aggtcaagct caccctcgcc 1140
ggttgcgagg agcgcaacgc ccagggtatg tgctcctgcg ccggtttcac ccagatcgtc 1200
aacgaggccc gcatccccgc ctgctccctc taa 1233
Claims (47)
1.一种热稳定性植酸酶，其是在野生型大肠杆菌植酸酶的氨基酸序列中引入二硫键而得，其中所述野生型大肠杆菌植酸酶的氨基酸序列如SEQ ID NO:1所示，且所述引入的二硫键为：
(1)SEQ ID NO:1的第34位上氨基酸残基突变而成的半胱氨酸和SEQ ID NO:1的第174位上氨基酸残基突变而成的半胱氨酸之间形成的二硫键；或者
(2)SEQ ID NO:1的第56位上氨基酸残基突变而成的半胱氨酸和SEQ ID NO:1的第103位上氨基酸残基突变而成的半胱氨酸之间形成的二硫键。
2.如权利要求1所述的热稳定性植酸酶，其中，该热稳定性植酸酶的氨基酸序列如SEQID NO:4所示。
3.如权利要求1所述的热稳定性植酸酶，其中，该热稳定性植酸酶的氨基酸序列如SEQID NO:5所示。
4.一种热稳定性植酸酶，其是在突变型大肠杆菌植酸酶的氨基酸序列中引入两个二硫键而得，其中所述突变型大肠杆菌植酸酶的氨基酸序列如SEQ ID NO:3、SEQ ID NO:79或SEQ ID NO:99所示，且所述引入的二硫键为：
(1)与SEQ ID NO:1的第56位对应的位置上的氨基酸残基突变而成的半胱氨酸和与SEQID NO:1的第103位对应的位置上的氨基酸残基突变而成的半胱氨酸之间形成的第一二硫键；以及
(2)与SEQ ID NO:1的第346位对应的位置上的氨基酸残基突变而成的半胱氨酸和与SEQ ID NO:1的第393位对应的位置上的氨基酸残基突变而成的半胱氨酸之间形成的第二二硫键。
5.如权利要求4所述的热稳定性植酸酶，其中，该热稳定性植酸酶的氨基酸序列如SEQID NO:22所示。
6.如权利要求4所述的热稳定性植酸酶，其中，该热稳定性植酸酶的氨基酸序列如SEQID NO:85所示。
7.如权利要求4所述的热稳定性植酸酶，其中，该热稳定性植酸酶的氨基酸序列如SEQID NO:105所示。
8.一种热稳定性植酸酶，其是在突变型大肠杆菌植酸酶的氨基酸序列中引入三个二硫键而得，其中所述突变型大肠杆菌植酸酶的氨基酸序列如SEQ ID NO:3所示，且所述引入的二硫键为：
(1)与SEQ ID NO:1的第56位对应的位置上的氨基酸残基突变而成的半胱氨酸和与SEQID NO:1的第103位对应的位置上的氨基酸残基突变而成的半胱氨酸之间形成的第一二硫键；
(2)与SEQ ID NO:1的第61位对应的位置上的氨基酸残基突变而成的半胱氨酸和与SEQID NO:1的第366位对应的位置上的氨基酸残基突变而成的半胱氨酸之间形成的第二二硫键；以及
(3)与SEQ ID NO:1的第346位对应的位置上的氨基酸残基突变而成的半胱氨酸和与SEQ ID NO:1的第393位对应的位置上的氨基酸残基突变而成的半胱氨酸之间形成的第三二硫键。
9.如权利要求8所述的热稳定性植酸酶，其中，该热稳定性植酸酶的氨基酸序列如SEQID NO:26所示。
10.一种热稳定性植酸酶，其是在突变型大肠杆菌植酸酶的氨基酸序列中引入二硫键而得，其中所述突变型大肠杆菌植酸酶的氨基酸序列如SEQ ID NO:79或SEQ ID NO:99所示，且所述引入的二硫键为：
与SEQ ID NO:1的第56位对应的位置上的氨基酸残基突变而成的半胱氨酸和与SEQ IDNO:1的第103位对应的位置上的氨基酸残基突变而成的半胱氨酸之间形成的二硫键。
11.如权利要求10所述的热稳定性植酸酶，其中，该热稳定性植酸酶的氨基酸序列如SEQ ID NO:80所示。
12.如权利要求10所述的热稳定性植酸酶，其中，该热稳定性植酸酶的氨基酸序列如SEQ ID NO:100所示。
13.如权利要求1-12任一项所述的热稳定性植酸酶，其中，该热稳定性植酸酶是通过在毕赤酵母或者黑曲霉宿主中异源表达而获得的。
14.一种多核苷酸，其编码如权利要求1-12中任一项所述的热稳定性植酸酶。
15.权利要求14的多核苷酸，其编码序列是为在毕赤酵母中表达而密码子优化的。
16.权利要求15的多核苷酸，其编码序列如SEQ ID NO:41、42、59和63中任一项所示。
17.权利要求14的多核苷酸，其编码序列是为在黑曲霉中表达而密码子优化的。
18.权利要求17的多核苷酸，其编码序列如SEQ ID NO:65、66、90、95、110和115中任一项所示。
19.一种宿主细胞，其包含权利要求14所述的多核苷酸。
20.权利要求19所述的宿主细胞，其中该宿主细胞是真菌细胞、细菌细胞或植物细胞。
21.权利要求20所述的宿主细胞，其为酵母细胞或丝状真菌细胞。
22.权利要求21所述的宿主细胞，其为毕赤酵母细胞。
23.权利要求22所述的宿主细胞，其包含权利要求15所述的多核苷酸。
24.权利要求22所述的宿主细胞，其包含权利要求16所述的多核苷酸。
25.权利要求21所述的宿主细胞，其为黑曲霉细胞。
26.权利要求25所述的宿主细胞，其包含权利要求17所述的多核苷酸。
27.权利要求25所述的宿主细胞，其包含权利要求18所述的多核苷酸。
28.一种提高植酸酶的热稳定性的方法，其包括对感兴趣的植酸酶的氨基酸序列或其编码核酸序列进行改变，其中所述感兴趣的植酸酶是野生型大肠杆菌植酸酶，所述野生型大肠杆菌植酸酶的氨基酸序列如SEQ ID NO:1所示，所述改变使得所述感兴趣的植酸酶中(1)SEQ ID NO:1的第34位上氨基酸残基突变而成的半胱氨酸和SEQ ID NO:1的第174位上氨基酸残基突变而成的半胱氨酸之间能够形成二硫键；或者
(2)SEQ ID NO:1的第56位上氨基酸残基突变而成的半胱氨酸和SEQ ID NO:1的第103位上氨基酸残基突变而成的半胱氨酸之间能够形成二硫键。
29.如权利要求28所述的方法，其中经过改变后的植酸酶的氨基酸序列、或者其编码核酸编码的氨基酸序列如SEQ ID NO:4所示。
30.如权利要求28所述的方法，其中经过改变后的植酸酶的氨基酸序列、或者其编码核酸编码的氨基酸序列如SEQ ID NO:5所示。
31.一种提高植酸酶的热稳定性的方法，其包括对感兴趣的植酸酶的氨基酸序列或其编码核酸序列进行改变，其中所述感兴趣的植酸酶是突变型大肠杆菌植酸酶，所述突变型大肠杆菌植酸酶的氨基酸序列如SEQ ID NO:3、SEQ ID NO:79或SEQ ID NO:99所示，所述改变使得所述感兴趣的植酸酶中
(1)与SEQ ID NO:1的第56位对应的位置上的氨基酸残基突变而成的半胱氨酸和与SEQID NO:1的第103位对应的位置上的氨基酸残基突变而成的半胱氨酸之间能够形成第一二硫键；以及
(2)与SEQ ID NO:1的第346位对应的位置上的氨基酸残基突变而成的半胱氨酸和与SEQ ID NO:1的第393位对应的位置上的氨基酸残基突变而成的半胱氨酸之间能够形成第二二硫键。
32.如权利要求31所述的方法，其中经过改变后的植酸酶的氨基酸序列、或者其编码核酸编码的氨基酸序列如SEQ ID NO:22所示。
33.如权利要求31所述的方法，其中经过改变后的植酸酶的氨基酸序列、或者其编码核酸编码的氨基酸序列如SEQ ID NO:85所示。
34.如权利要求31所述的方法，其中经过改变后的植酸酶的氨基酸序列、或者其编码核酸编码的氨基酸序列如SEQ ID NO:105所示。
35.一种提高植酸酶的热稳定性的方法，其包括对感兴趣的植酸酶的氨基酸序列或其编码核酸序列进行改变，其中所述感兴趣的植酸酶是突变型大肠杆菌植酸酶，所述突变型大肠杆菌植酸酶的氨基酸序列如SEQ ID NO:3所示，所述改变使得所述感兴趣的植酸酶中(1)与SEQ ID NO:1的第56位对应的位置上的氨基酸残基突变而成的半胱氨酸和与SEQ IDNO:1的第103位对应的位置上的氨基酸残基突变而成的半胱氨酸之间能够形成第一二硫键；
(2)与SEQ ID NO:1的第61位对应的位置上的氨基酸残基突变而成的半胱氨酸和与SEQID NO:1的第366位对应的位置上的氨基酸残基突变而成的半胱氨酸之间能够形成第二二硫键；以及
(3)与SEQ ID NO:1的第346位对应的位置上的氨基酸残基突变而成的半胱氨酸和与SEQ ID NO:1的第393位对应的位置上的氨基酸残基突变而成的半胱氨酸之间能够形成第三二硫键。
36.如权利要求35所述的方法，其中经过改变后的植酸酶的氨基酸序列、或者其编码核酸编码的氨基酸序列如SEQ ID NO:26所示。
37.一种提高植酸酶的热稳定性的方法，其包括对感兴趣的植酸酶的氨基酸序列或其编码核酸序列进行改变，其中所述感兴趣的植酸酶是突变型大肠杆菌植酸酶，所述突变型大肠杆菌植酸酶的氨基酸序列如SEQ ID NO:79或SEQ ID NO:99所示，所述改变使得所述感兴趣的植酸酶中
与SEQ ID NO:1的第56位对应的位置上的氨基酸残基突变而成的半胱氨酸和与SEQ IDNO:1的第103位对应的位置上的氨基酸残基突变而成的半胱氨酸之间能够形成二硫键。
38.如权利要求37所述的方法，其中经过改变后的植酸酶的氨基酸序列、或者其编码核酸编码的氨基酸序列如SEQ ID NO:80所示。
39.如权利要求37所述的方法，其中经过改变后的植酸酶的氨基酸序列、或者其编码核酸编码的氨基酸序列如SEQ ID NO:100所示。
40.如权利要求28-39中任一项所述的方法，其中该方法还包括生成包含经改造的氨基酸序列的植酸酶，并将其置于容许二硫键形成的环境中。
41.如权利要求40所述的方法，其中生成包含经改造的氨基酸序列的植酸酶包括将编码该植酸酶的多核苷酸在宿主细胞中表达。
42.如权利要求41所述的方法，其中所述宿主细胞是真菌细胞。
43.如权利要求42所述的方法，其中所述宿主细胞是酵母细胞或丝状真菌细胞。
44.如权利要求43所述的方法，其中所述宿主细胞是毕赤酵母细胞。
45.如权利要求44所述的方法，其中编码核酸的核苷酸序列如SEQ ID NO:41、42、59和63中任一项所示。
46.如权利要求43所述的方法，其中所述宿主细胞是黑曲霉细胞。
47.如权利要求46所述的方法，其中编码核酸的核苷酸序列如SEQ ID NO:65、66、90、95、110和115中任一项所示。
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| CN113699134B (zh) * | 2020-05-22 | 2024-04-05 | 潍坊康地恩生物科技有限公司 | 植酸酶突变体 |
| KR20230050402A (ko) * | 2020-08-13 | 2023-04-14 | 노보자임스 에이/에스 | 피타제 변이체 및 이를 암호화하는 폴리뉴클레오티드 |
| EP4119658A1 (en) * | 2021-07-16 | 2023-01-18 | AB Enzymes Oy | Phytase variants |
| EP4119661A1 (en) * | 2021-07-16 | 2023-01-18 | AB Enzymes Oy | Phytase variants with improved stability and ip4 activity |
| EP4370670A1 (en) * | 2021-07-16 | 2024-05-22 | AB Enzymes Oy | Phytase variants with improved stability and ip4 activity |
| KR20230048891A (ko) * | 2021-10-05 | 2023-04-12 | 씨제이제일제당 (주) | 피타아제 변이체 |
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