專利名稱：體內遞送成骨誘導性制劑的聚合物包裹物的制作方法
技術領域：
本發(fā)明涉及一種聚合物包裹物(polymeric wrap)，它被設計成能夠覆蓋矯形外科裝置并在體內對植入附近的組織提供成骨誘導性制劑?？稍谥踩胙b置之前或在將裝置植入患者的同時將聚合物包裹物施加于矯形外科裝置。在本發(fā)明的一個實施方式中，以覆蓋矯形裝置外部形狀的預成形組合物的形式提供包裹物。在本發(fā)明另一個實施方式中，聚合物包裹物包括多個聚合物層或由多個聚合物層構成，各個聚合物層包含不同的成骨誘導劑和/或不同濃度的成骨誘導劑?；蛘?，聚合物包裹物的多個聚合物層具有不同的降解速率，從而以由特定聚合物的降解速率所指定的不同速率釋放成骨誘導劑。
背景技術：
在美國，每年要對需要生物醫(yī)學植入物的患者進行數以千計的植入手術。例如，僅在美國每年就進行了168,000例以上的全髖關節(jié)置換手術。Shindle，M.等，BioMechanics，11(2)22-32(2004)。
不幸的是，每年有許多植入外科手術需要修復手術來校正植入裝置發(fā)生的缺陷。例如，如Croci等關于骨腫瘤的分段切除術的論述，骨腫瘤切除術后患者存活率的增加導致更需要進行植入裝置的修復手術，而過去由于不成功的腫瘤控制不常出現上述結果。Croci等，Rev.Hosp.Clin.Fac.Med.S.Paulo，55(5)169-176(2000)。
設計成能夠將成骨誘導劑遞送至肌骨骼植入裝置附近的裝置尤其適用于初次手術和修復手術，用于防止植入裝置附近骨質溶解的發(fā)生。這種性質的裝置也可用于避免以后進行修復手術。設計成能夠將成骨誘導劑遞送至肌骨骼植入物附近的裝置尤其適用于諸如以下手術的初次手術和修復手術肱骨元件柄(stem)的肩關節(jié)手術；肱骨和尺骨元件柄的肘關節(jié)手術；尺骨元件柄的腕關節(jié)手術；與髖臼杯(acetabular cup)植入物相關和與接骨螺釘相關的股骨柄的髖關節(jié)手術；股骨柄、股骨元件關節(jié)背側、脛骨柄、脛骨盤下側以及髕骨背側的膝關節(jié)手術；以及全肩、全髖和全膝置換術。
發(fā)明概述因此，本領域仍然需要與矯形裝置一起植入并提供成骨誘導性制劑以立即方式或在延長的時間范圍內速釋或緩釋的成骨誘導性制劑。申請人在本文中描述了生物醫(yī)學植入物裝置的優(yōu)選覆蓋物(covering)，能夠滿足本領域對在矯形外科植入物裝置植入部位附近提供成骨誘導性制劑的覆蓋物的需要。
本發(fā)明的一個實施方式提供了一種聚合物包裹物，它包含至少兩個可生物降解的聚合物片層，其中，所述至少兩個可生物降解的聚合物片層相互結合，所述多層聚合物包裹物還包含至少一種成骨誘導性制劑。
本發(fā)明另一個實施方式提供了一種預防或治療植入患者發(fā)生溶骨性病變的方法，該方法包括將含有成骨誘導性制劑的聚合物包裹物植入所述患者中。本發(fā)明另一個實施方式包括含有上述聚合物包裹物的成套工具。
通過閱讀下面的詳細說明，本領域技術人員容易明白本發(fā)明實施方式的這些和其它特征。
附圖簡要說明

圖1A-B顯示了一種施用于股骨柄植入物的聚合物包裹物。如圖1A所示，將包裹物設計成套筒，以在植入之前覆蓋矯形外科裝置的外表面。如圖1B所示，植入之前包裹物貼合在矯形外科裝置的外部。
圖2A-B顯示了一種被設計成覆蓋髖臼杯暴露面的聚合物包裹物。如圖1A所示，將包裹物設計成髖臼杯形狀。如圖1B所示，植入之前聚合物包裹物基本上覆蓋髖臼杯的外部。包裹物可任選地被有助于將該髖臼杯固定于內源性骨的物品穿刺，例如設計用于固定植入物的骨或其它螺釘。
優(yōu)選實施方式的詳細描述為了促進對本發(fā)明的理解，現在將參考優(yōu)選實施方式并用具體語言來描述這些實施方式。本文所用的術語僅僅是為了描述具體實施方式
，而不旨在限制本發(fā)明的范圍。除非文中清楚地另有說明，本說明書通篇所用單數形式“一種”、“一個”和“這個”包括復數涵義。因此，例如，“一個植入物”包括多個植入物以及單個植入物，“一種成骨誘導劑”表示一種或多種誘導劑以及本領域技術人員已知的等價形式，等等。
除非另有說明，本文所用的所有科技術語具有與本發(fā)明所屬領域技術人員通常所理解相同的含義。雖然可使用類似于或等價于本文所述的任何方法和材料來實施或測試本發(fā)明，但現在將描述優(yōu)選的方法、裝置和材料。本文提及的所有出版物的引用是為了描述和說明出版物中報道的并且可與本發(fā)明聯(lián)用的各種植入物、成骨誘導劑和其它部件。所有這些都不應解釋為承認本發(fā)明沒有居于這些現有技術的內容之前的新穎性。
如本文所用，“可生物利用的”指在患者體內提供成骨誘導劑時，所述成骨誘導劑能夠保留生物活性。保留生物活性表示與植入之前的成骨誘導劑活性相比，成骨誘導劑保留至少25％，優(yōu)選至少50％，更優(yōu)選至少75％，最優(yōu)選至少95％或更多的成骨誘導劑活性。
如本文所用，“成熟多肽”指多肽的翻譯后加工形式。例如，宿主表達系統(tǒng)中表達后，成熟多肽可缺少一個或多個信號肽、前肽原和前肽結構域。生物領域技術人員明白信號肽、前肽原和前肽結構域的含義。
如本文所用，“速釋”表示在相當短的時間內提供成骨誘導性制劑的本發(fā)明制劑。
如本文所用，“緩釋”指被設計成在延長的時間范圍內以可生物利用的形式提供相對恒定濃度的成骨誘導性制劑的本發(fā)明制劑。
如本文所用，“可生物降解的”指體內應用期間降解的聚合物。在本發(fā)明的一個實施方式中，聚合物降解產生聚合物單體亞單元。
如本文所用，“聚合物包裹物”指包括一個或多個聚合物層、或者由一個或多個聚合物層構成的片層，各個聚合物層任選地包含一種或多種成骨誘導劑，其中，所述成骨誘導劑以類似或不同的濃度存在于多個聚合物層中。如果聚合物包裹物包含多個聚合物層或由多個聚合物層構成，多個聚合物層可分別產生并組合，以形成聚合物包裹物。
如本文所用，“矯形外科裝置”指經外科手術引入患者的任何生物醫(yī)學植入物，可設計成與骨骼系統(tǒng)或身體關節(jié)聯(lián)合起作用。
本發(fā)明實施方式包括聚合物包裹物，多層聚合物包裹物優(yōu)選包含至少兩個可生物降解的聚合物片層。所述至少兩個可生物降解的聚合物片層優(yōu)選相互結合，所述多層聚合物包裹物還包含至少一種成骨誘導性制劑。
本發(fā)明成骨誘導性制劑優(yōu)選包含一種或多種誘導內源性骨、或與內源性骨相關的組織如結締組織和血管組織生長的成骨誘導劑。此外，提供用于抑制骨再吸收的成骨誘導劑。成骨誘導性制劑包含成骨誘導劑，例如一種或多種骨形態(tài)發(fā)生蛋白(BMP)、一種或多種結締組織生長因子(CTGF)、一種或多種血管內皮生長因子(VEGF)、護骨蛋白(OPG)、Periostin以及一種或多種轉化生長因子-β(TGF-β)多核苷酸和多肽。聚合物包裹物中提供的成骨誘導劑是可生物利用的形式，它是速釋或緩釋制劑的組成成分。
在本發(fā)明的一個實施方式中，聚合物包裹物包含可生物降解的聚合物，它基于含成骨誘導性制劑的可生物降解的聚合物的降解速率釋放成骨誘導性制劑。本發(fā)明還提供了預防和治療患者矯形外科植入物附近溶骨性病變形成的方法。本發(fā)明也提供了增加植入部位周圍組織生長的方法。
本發(fā)明包括聚合物包裹物，其包含能促進內源性骨、結締組織和血管組織生長以及防止骨再吸收的成骨誘導性制劑。本發(fā)明中使用的成骨誘導性制劑包含一種或多種成骨誘導劑。成骨誘導性制劑可摻入形成聚合物包裹物的聚合物組合物中。或者，可在植入之前將成骨誘導性制劑施加在聚合物包裹物的外表面上。
在本發(fā)明的一個實施方式中，將聚合物包裹物中使用的成骨誘導性制劑與緩釋聚合物混合，并模塑成預成形固體聚合物包裹物?？刹捎媚＞咝纬晒腆w聚合物包裹物，過程是將液體聚合物加入到模具中，然后將聚合物溶液固化或固定形成預成形聚合物片層。優(yōu)選地，可通過增加聚合物的抗生物降解性，例如通過引入或增加可生物降解的聚合物組合物中所含生物穩(wěn)定聚合物的百分比來操縱成骨誘導劑從聚合物包裹物緩慢釋放的持續(xù)時間。
在本發(fā)明另一優(yōu)選實施方式中，聚合物包裹物由在植入之前單獨施加在矯形外科裝置上的任選預成形的一層或多層聚合物組成。所述在植入之前施加在矯形外科裝置上的一層或多層可用于形成與矯形外科裝置一起植入的多層聚合物包裹物。任選地，配制多層包裹物的各個聚合物層，使其具有不同的降解特征。使用具有不同降解速率的多層聚合物包裹物使本領域技術人員能夠構建具有定制降解特征的聚合物包裹物。
例如，如果患者在初始相需要大劑量成骨誘導劑并在延長的時間段內需要持續(xù)濃度的成骨誘導劑，則可將多層包裹物配制成在具有高生物降解速率的聚合物外層中含有高濃度成骨誘導劑，從而在開始時釋放高濃度成骨誘導劑，以及含有成骨誘導劑和低降解速率的一個或多個聚合物內層?；蛘?，如果確定患者將受益于延長的成骨誘導劑釋放持續(xù)時間，可將多層聚合物包裹物配制成任選地含有成骨誘導劑的一個或多個可生物降解的聚合物外層和含有體內生物降解速率降低的成骨誘導劑的一個或多個可生物降解的聚合物內層。這樣，聚合物包裹物可提供相對持續(xù)的成骨誘導劑來源。所述多層聚合物包裹物可包含引入聚合物包裹物的成骨誘導性制劑中的一種或多種成骨誘導劑。
在本發(fā)明另一個實施方式中，多層聚合物包裹物包含至少一種成骨誘導劑或由至少一種成骨誘導劑組成，它們在這個聚合物包裹物的各個聚合物層中濃度不同。例如，多層可生物降解的聚合物包裹物的一個或多個內層可包含較高濃度的成骨誘導劑，而可生物降解的聚合物包裹物的一個或多個外層可包含較低濃度的成骨誘導劑。在該實施方式中，濃度平穩(wěn)增加的成骨誘導劑被引入患者體內?；蛘撸敵晒钦T導劑在體內隨著時間推移活性降低時，含較高濃度成骨誘導劑的聚合物包裹物內層將有助于補償內層內層中一種或多種成骨誘導劑的活性降低，從而在可生物降解的聚合物包裹物的整個使用壽命期間提供相對恒定濃度的成骨誘導劑(活性方面)。換言之，多層聚合物包裹物內層中較高濃度的成骨誘導劑可補償可生物利用的活性成骨誘導劑隨時間推移的濃度降低。
本發(fā)明另一方面涉及摻入聚合物包裹物中的成骨誘導性制劑。成骨誘導性制劑優(yōu)選包含一種或多種成骨誘導劑，并提供作為速釋或緩釋制劑的一種或多種可生物利用形式的試劑。成骨誘導性制劑還任選地包含一種或多種以下成分抗生素、載體、骨髓抽吸物、骨髓濃縮物、脫礦物質骨基質、免疫抑制劑、提高等張性(isotonicity)和化學穩(wěn)定性的試劑、以及一種或多種(包括所有)所述成分的組合。
本發(fā)明實施方式的成骨誘導性制劑可以是速釋制劑或緩釋制劑。植入外科領域技術人員能根據諸如年齡和身體活動水平等因素確定患者適合速釋制劑或是緩釋制劑。因此，本發(fā)明成骨誘導性制劑可以是速釋制劑、緩釋制劑或二者兼有。
代表性的速釋制劑是液體制劑，它包含施加在聚合物包裹物表面的至少一種成骨誘導劑。液體制劑提供可生物利用形式的成骨誘導劑，以液體制劑的流體性質如在植入部位的擴散速率、內源性流體的影響等確定的速率釋放。合適的液體制劑的例子包含水、鹽水或不會誘導宿主免疫反應的其它可接受的流體介質。
本發(fā)明速釋制劑提供在相當短的時間內釋放的成骨誘導性制劑，雖然諸如體液親近性(proximity)、制劑組成等因素將影響成骨誘導性從制劑的釋放時間。但是，速釋制劑被設計成不能在延長的時間段內保留一種或多種成骨誘導劑，并且通常缺少作為速釋制劑的組成成分的可生物降解的聚合物。
在本發(fā)明另一個實施方式中，成骨誘導性制劑可以是緩釋制劑，它在延長的時間范圍內提供可生物利用形式的成骨誘導性制劑。緩釋制劑的釋放持續(xù)時間由制劑的性質和上述其它因素如體液親近性、以及制劑施用密度、含成骨誘導性制劑的可生物降解聚合物的降解速率和其它因素決定。然而，緩釋制劑被設計成可在延長的時間范圍內提供可生物利用形式的濃度相對恒定的制劑中的成骨誘導劑。聚合物包裹物中使用的可生物降解的緩釋聚合物是本領域已知的，包括但不限于聚丙交酯、聚乙交酯、聚己酸內酯、聚酐、聚酰胺、聚氨酯、聚酯酰胺、聚原酸酯、聚二烷酮、聚縮醛、聚縮酮、聚碳酸酯、聚原碳酸酯、聚膦腈、聚羥基丁酸酯、聚羥基戊酸酯、聚亞烷基草酸酯、聚亞烷基琥珀酸酯、聚(蘋果酸)、聚(氨基酸)、聚乙烯吡咯烷酮、聚乙二醇、聚羥基纖維素、殼多糖、殼聚糖、聚(L-乳酸)、聚(丙交酯-共-乙交酯)、聚(羥基丁酸酯-共-戊酸酯)以及上述材料的共聚物、三聚物、或者它們的組合或混合物。可生物降解聚合物的釋放特征還可通過摻入能夠影響聚合物組合物生物降解速率的生物穩(wěn)定聚合物進行調整?？蓳饺肟缮锝到饩酆衔飶亩绊懮锝到馑俾实纳锓€(wěn)定聚合物包括但不限于硅氧烷、聚酯、乙烯基均聚物和共聚物、丙烯酸酯均聚物和共聚物、聚醚以及纖維素類。
可生物降解的聚合物可以是固體形式的聚合物或者可以是施加后在適當時間內固化的液體聚合物。合適的液體聚合物制劑包括但不限于諸如美國專利5,744,153、4,938,763、5,278,201和5,278,202中所述的聚合物組合物，它們的全部內容參考包括在此。這些專利描述了能夠用作控釋藥物組合物或用作植入物的液體聚合物組合物。該液體預聚物具有至少一個可聚合的烯鍵式不飽和基團(例如，丙烯酸-酯-封端的預聚物)。若采用固化劑，通常在臨用前將固化劑加入到組合物中。在固化或固定預聚物之前將成骨誘導劑加入到液體預聚物中。引入固化劑之后，預聚物在短時間內保持液體狀態(tài)。然后，混合物固化形成固體組合物?？蓪⒁后w聚合物組合物以液體形式給予患者，然后在引入部位固化或固定形成固體聚合物涂覆組合物?；蛘撸蓪⒁后w聚合物注入預成形模具中以形成聚合物包裹物，在植入患者之前預成形以貼合在矯形外科裝置的外形上?？紤]了聚合物的可生物降解形式，也考慮了能夠影響聚合物生物降解速率的可生物降解聚合物和生物穩(wěn)定聚合物的混合物。
本發(fā)明成骨誘導性制劑還考慮使用在延長的時間段內保持成骨誘導劑穩(wěn)定性的水性或非水性肽制劑。用于長期穩(wěn)定成骨誘導劑的水性和非水性制劑的非限制性例子包括美國專利5,916,582、5,932,547和5,981,489提供的制劑，它們各自的內容參考包括在此。
將一定量液體緩釋聚合物組合物例如通過噴霧、涂抹或噴濺分配到聚合物包裹物上，給予后液體制劑固化形成緩釋制劑。
在本發(fā)明另一個實施方式中，用于體內遞送成骨誘導性制劑的液體組合物包含成骨誘導劑與不溶于水的生物相容性聚合物的偶聯(lián)物，所得聚合物活性物質偶聯(lián)物在生物相容性溶劑中溶解形成液體聚合物體系。此外，液體聚合物體系還可包含不與成骨誘導劑偶聯(lián)的不溶于水的生物相容性聚合物。在本發(fā)明的一個實施方式中，這些液體組合物可以液體形式引入對象體內。然后，液體組合物在原位固化或凝固成控釋植入物，其中成骨誘導劑偶聯(lián)于固體基質聚合物。
可以在成骨誘導性制劑中作為分離的多肽或多核苷酸給予本發(fā)明實施方式的成骨誘導劑。分離的成骨誘導劑的多核苷酸組成包括但不限于骨形態(tài)發(fā)生蛋白(BMP)、血管內皮生長因子(VEGF)、結締組織生長因子(CTGF)、護骨蛋白、Periostin和轉化生長因子β(TGF-β)多核苷酸。成骨誘導劑的多核苷酸組成包括但不限于攜帶編碼感興趣成骨誘導性多肽的多核苷酸的基因治療載體?；蛑委煼椒ㄐ枰刹僮鞯剡B接或結合于啟動子和靶組織表達成骨誘導性多肽所需的任何其它遺傳元件的編碼成骨誘導性多肽的多核苷酸。這些基因療法和遞送技術是本領域已知的，例如參見國際公開號WO90/11092，其內容參考包括在此。合適的基因治療載體包括但不限于，不整合入宿主基因組的基因治療載體?；蛘撸线m的基因治療載體包括但不限于，整合入宿主基因組的基因治療載體。
在一個實施方式中，以質粒制劑的形式遞送本發(fā)明多核苷酸。質粒DNA或RNA制劑指不含輔助、促進或有助于進入細胞的任何遞送運載體的編碼成骨誘導性多肽的序列，包括病毒序列、病毒顆粒、脂質體制劑、lipofectin或沉淀劑等。任選地，本發(fā)明基因治療組合物可以脂質體制劑和lipofectin制劑的形式遞送，這些制劑可通過本領域技術人員熟知的方法制備。一般方法參見，例如美國專利5,593,972、5,589,466和5,580,859，其內容參考包括在此。
基因治療載體還包括合適的腺病毒載體，包括但不限于Kozarsky和Wilson，Curr.Opin.Genet.Devel.，3499-503(1993)；Rosenfeld等，Cell，68143-155(1992)；Engelhardt等，Human Genet.Ther.，4759-769(1993)；Yang等，Nature Genet.，7362-369(1994)；Wilson等，Nature，365691-692(1993)；和美國專利5,652,224所述的載體，其內容參考包括在此。
分離的成骨誘導劑的多肽組成包括但不限于分離的骨形態(tài)發(fā)生蛋白(BMP)、血管內皮生長因子(VEGF)、結締組織生長因子(CTGF)、護骨蛋白、Periostin和轉化生長因子β(TGF-β)多肽。成骨誘導劑的多肽組成包括但不限于分離的全長蛋白質、蛋白質片段或變體。在本發(fā)明一個優(yōu)選的實施方式中，成骨誘導劑多肽片段包含分離的全長多肽的前肽形式或由其構成。在本發(fā)明一個尤其優(yōu)選的實施方式中，成骨誘導劑的多肽片段包含分離的全長多肽的成熟形式或由其構成。還優(yōu)選編碼成骨誘導劑的前肽和成熟多肽的多核苷酸。
本發(fā)明成骨誘導劑的變體包括但不限于設計成在體內增加成骨誘導劑活性持續(xù)時間的蛋白質變體。變體成骨誘導劑的優(yōu)選實施方式包括但不限于偶聯(lián)于聚乙二醇(PEG)部分以增加其體內半衰期(也稱為聚乙二醇化)的全長蛋白質或其片段。聚乙二醇化多肽的方法是本領域眾所周知的(例如，參見美國專利6,552,170和歐洲專利0,401,384，作為制備聚乙二醇化多肽的方法的例子)。
在本發(fā)明另一個實施方式中，提供的成骨誘導劑是成骨誘導性制劑中的融合蛋白。在一個實施方式中，成骨誘導劑是具有人IgG的Fc部分的融合蛋白。在本發(fā)明另一個實施方式中，本發(fā)明成骨誘導劑是異源二聚體或同源二聚體或多聚體。優(yōu)選的融合蛋白的例子包括但不限于成熟成骨誘導性多肽和人免疫球蛋白G(IgG)的Fc部分的配體融合物。制備融合蛋白和編碼其的構建物的方法本領域眾所周知的。
包含在成骨誘導性制劑中的本發(fā)明成骨誘導劑是無菌的。在一個非限制性方法中，例如通過濾過除菌濾膜(例如，0.2微米膜或濾器)可容易地實現滅菌。
在本發(fā)明的一個實施方式中，提供的聚合物包裹物在包裹物內不包含成骨誘導性制劑。在本發(fā)明該實施方式中，在將包裹物植入患者之前將成骨誘導性制劑引入聚合物包裹物的表面。或者，將成骨誘導性制劑加到多層聚合物包裹物的可生物降解的聚合物片層之間。在這種情況下，通常將成骨誘導劑加入具有無菌入口的容器中，例如具有可用皮下注射針刺穿的塞子的靜脈輸液袋或瓶。在一個實施方式中，將成骨誘導劑和制備的成骨誘導性制劑以水溶液或以可重建凍干制劑的形式儲存在獨立的容器中，例如密封安瓿或小瓶。作為凍干制劑的一個例子，在10毫升小瓶中加入5毫升過濾除菌的1％(w/v)成骨誘導劑水溶液，然后凍干所得混合物。在以合適的溶液形式施加之前，通過重建凍干試劑制備成骨誘導劑，與制備的成骨誘導性制劑混合后，在植入患者之前或同時施加在聚合物包裹物的表面或施加在多層聚合物包裹物的聚合物層之間。通過將聚合物包裹物浸入成骨誘導性制劑中，將成骨誘導性制劑噴涂在聚合物包裹物的表面上，或通過任何其它施加方式來完成施加。
本領域技術人員將理解，成骨誘導劑的濃度可根據所需的成骨誘導長度或程度而變化。類似地，本領域技術人員將理解，可通過操縱含緩釋制劑的組成，例如調節(jié)緩釋聚合物中生物穩(wěn)定聚合物的百分比，來調節(jié)緩釋持續(xù)時間。
提供可用于形成體內遞送成骨誘導劑的聚合物片層的液體組合物的方法是將活性物質與不溶于水的生物相容性聚合物偶聯(lián)并將所得聚合物-活性物質偶聯(lián)物溶解在生物相容性溶劑中，形成類似于美國專利4,938,763、5,278,201和5,278,202中所述的液體聚合物體系。不溶于水的生物相容性聚合物可以是上述專利中所述的聚合物或相關共聚物。此外，液體聚合物體系還可包含沒有偶聯(lián)活性物質的不溶于水的生物相容性聚合物。在本發(fā)明的一個實施方式中，這些液體組合物可以液體形式引入對象體內。然后在原位固化或凝固液體組合物以形成控釋植入物，其中活性物質偶聯(lián)于固體基質聚合物。
本發(fā)明成骨誘導性制劑任選地還可任選地包含脫礦物質骨基質組合物(后文中稱為“DBM”組合物)、骨髓抽吸物、骨髓濃縮物、或這些物質的組合或排列。制備DBM的方法是本領域眾所周知的，DBM可根據O′Leary等(美國專利5,073,373)的內容獲得，或者(例如)以AlloGro從供應商如AlloSource(Centennial，CO)購得。獲得骨髓抽吸物的方法及有利于提取骨髓抽吸物的裝置是本領域眾所周知的，例如參見Turkel等的美國專利5,257,632。
本發(fā)明成骨誘導性制劑任選地還包含可與成骨誘導劑一起給予的抗生素。如Vehmeyer等所述，由于引入了來自活體供者的受污染的同種異體移植物組織，存在發(fā)生細菌污染的可能性。Vehmeyer，SB等，Acta Orthop Scand.，73(2)165-169(2002)。本發(fā)明抗生素也可與成骨誘導性制劑共同給予以防止植入手術期間引入患者的專性病原體或機會病原體感染。
本發(fā)明成骨誘導性制劑中使用的抗生素包括但不限于阿莫西林、β-內酰胺酶、氨基糖苷類、β-內酰胺(糖肽)、克林霉素、氯霉素、頭孢菌素、環(huán)丙沙星、紅霉素、氟喹諾酮類、大環(huán)內酯類、甲硝唑、青霉素類、喹諾酮類、雷帕霉素、利福平、鏈霉素、磺胺、四環(huán)素類、甲氧芐啶、甲氧芐啶-磺胺甲唑和萬古霉素。此外，由于醫(yī)院感染或進行外科手術的場所的其它特異性因素，植入外科領域技術人員或進行植入手術的場所的管理者偏愛引入一種或多種上述抗生素。因此，本發(fā)明還考慮，本發(fā)明成骨誘導性制劑中可包含一種或多種本文所述抗生素以及一種或多種這些抗生素的任意組合。
本發(fā)明成骨誘導性制劑任選地還包含免疫抑制劑，尤其是將同種異體移植物組合物給予患者的情況下?？膳c本發(fā)明成骨誘導性制劑聯(lián)合給予的合適的免疫抑制劑包括但不限于類固醇、環(huán)孢霉素、環(huán)孢霉素類似物、環(huán)磷酰胺、甲基潑尼松、潑尼松、硫唑嘌呤、FK-506、15-脫氧精胍菌素、以及通過抑制效應T細胞功能起作用的其它免疫抑制劑?？膳c本發(fā)明成骨誘導性制劑聯(lián)合給予的其它免疫抑制劑包括但不限于潑尼松龍、甲氨蝶呤、沙利度胺、甲氧沙林、雷帕霉素、來氟米特、咪唑立賓(布累迪寧TM)、布喹那、脫氧精胍菌素和azaspirane(SKF105685)、Orthoclone OKTTM3(莫羅單抗-CD3)、SandimmuneTM、NeoralTM、SangdyaTM(環(huán)孢霉素)、PrografTM(FK506、他克莫司)、CellceptTM(麥考酚酸嗎乙酯，其活性代謝物是麥考酚酸)、ImuranTM(硫唑嘌呤)、糖皮質激素、腎上腺皮質類固醇如DeltasoneTM(潑尼松)和HydeltrasolTM(潑尼松龍)、FolexTM和MexateTM(甲氨蝶呤)、Oxsoralen-UltraTM(甲氧沙林)和RapamuenTM(西羅莫司)。
本發(fā)明成骨誘導性制劑任選地還包含，運載體如水、鹽水、林格溶液、磷酸鈣基載體或右旋糖溶液。本文中也可使用非水性運載體如非揮發(fā)性油和油酸乙酯，以及脂質體。
在本發(fā)明的一個實施方式中，膠原可用作載體或作為用作遞送成骨誘導性制劑的聚合物包裹物的基質。在本發(fā)明另一個實施方式中，將膠原與糖胺聚糖聯(lián)合用作成骨誘導性制劑的載體，如美國專利5,922,356所述，其內容參考包括在此。制劑中糖胺聚糖的含量優(yōu)選小于40％的制劑重量，更優(yōu)選1-10重量％。膠原優(yōu)選占20-95％的制劑重量，更優(yōu)選40-60重量％。
任何膠原均可用作成骨誘導性制劑的載體。可用作載體的合適的膠原的例子包括但不限于I型人膠原、II型人膠原、III型人膠原、IV型人膠原、V型人膠原、VI型人膠原、VII型人膠原、VIII型人膠原、IX型人膠原、X型人膠原、XI型人膠原、XII型人膠原、XIII型人膠原、XIV型人膠原、XV型人膠原、XVI型人膠原、XVII型人膠原、XVIII型人膠原、XIX型人膠原、XXI型人膠原、XXII人膠原型、XXIII型人膠原、XXIV型人膠原、XXV型人膠原、XXVI型人膠原、XXVII型人膠原和XXVIII人膠原型以及它們的組合?？捎糜诒景l(fā)明的膠原載體還包含任何上述膠原類型的異源和同源三聚體或由其構成。在本發(fā)明一個優(yōu)選的實施方式中，膠原載體包含I型人膠原、II型人膠原和III型人膠原的異源或同源三聚體或其組合，或者由其構成。
在本發(fā)明另一個實施方式中，上述膠原基本上組成了聚合物包裹物。例如，形成聚合物包裹物的膠原摻入了包含一種或多種成骨誘導劑的成骨誘導性制劑。將含有至少一種成骨誘導劑的膠原包裹物引入患者，植入時包裹物基本上覆蓋矯形外科裝置。植入后，膠原包裹物釋放含有成骨誘導劑的成骨誘導性制劑。有用的膠原包裹物的例子包括但不限于膠原片層和牛源性重組膠原片層。在本發(fā)明另一個實施方式中，膠原包裹物被一種或多種可生物降解的聚合物層所覆蓋，從而形成不同的多層聚合物片材。
用作聚合物包裹物載體的膠原可以是人或非人源性的，重組或非重組的。在本發(fā)明一個優(yōu)選的實施方式中，用作載體的膠原是重組膠原。制備重組膠原的方法是本領域已知的，例如，利用諸如美國專利5,895,833(轉基因生產)，J.Myllyharju等，Biotechnology of Extracellular Matrix，353-357(2000)(在巴斯德畢赤酵母中產生重組人I-III型(production of recombinant human types I-III inPichia pastoris))，Wong Po Foo，C.等，Adv.Drug Del.Rev.，541131-1143(2002)，或Toman，P.D.等，J.Biol.Chem.，275(30)23303-23309(2001)等所述的重組方法，上述文獻的內容參考包括在此?；蛘?，例如從FibroGen(San Francisco，California)購得重組人膠原類型。
本發(fā)明成骨誘導性制劑還任選地包含提高等張性和化學穩(wěn)定性的物質。這些物質在所用劑量和濃度下對患者無毒，并包括緩沖劑，例如磷酸鹽、檸檬酸鹽、琥珀酸鹽、醋酸以及其它有機酸或其鹽；抗氧化劑，例如抗壞血酸；小分子量(小于約10個殘基)多肽，例如多聚精氨酸或三肽；蛋白質，例如血清白蛋白、明膠或免疫球蛋白類；氨基酸，例如甘氨酸、谷氨酸、天冬氨酸或精氨酸；單糖、二糖和其它碳水化合物，包括纖維素或其衍生物、葡萄糖、甘露糖或糊精；螯合劑，例如EDTA；糖醇，例如甘露醇或山梨糖醇；抗衡離子，例如鈉；和/或非離子型表面活性劑如聚山梨酯、泊洛沙姆或PEG。
本發(fā)明成骨誘導性制劑還包含分離的成骨誘導劑。分離的成骨誘導劑可促進內源性骨生長，或有助于防止植入物周圍骨組織被破骨細胞再吸收。本發(fā)明分離的成骨誘導劑是多肽或多核苷酸形式。本發(fā)明分離的成骨誘導劑包括全長蛋白質及其片段、以及本文所提供的分離的成骨誘導劑的多肽變體或突變體。
在本發(fā)明另一個實施方式中，成骨誘導劑多肽是異源二聚體或同源二聚體，以及多聚體或其組合。
重組表達的蛋白質可以是天然形式、截短類似物、突變蛋白、融合蛋白、以及能夠誘導骨、軟骨或其它類型的組織形成的其它構建形式，如體外或離體生物測定和體內植入哺乳動物(包括人)所顯示的那樣。
本發(fā)明還考慮使用與本文提供的分離的成骨誘導劑多核苷酸和多肽具有至少95％同源、更優(yōu)選97％、甚至更優(yōu)選99％同源的多核苷酸和多肽。典型的成骨誘導性制劑包含在pH約3-8下，濃度約為0.1-100毫克/毫升、優(yōu)選1-10毫克/毫升的分離的成骨誘導劑。
在本發(fā)明一個實施方式中，分離的成骨誘導劑包含骨形態(tài)發(fā)生蛋白(“BMP”)家族成員的一種或多種多核苷酸或多肽。BMP是一類認為對內源性骨組織具有成骨誘導活性或促進生長活性的蛋白質。BMP家族已知成員包括但不限于BMP-1、BMP-2、BMP-3、BMP-4、BMP-5、BMP-6、BMP-7、BMP-8、BMP-9、BMP-10、BMP-11、BMP-12、BMP-13、BMP-15、BMP-16、BMP-17和BMP-18。
可用作分離的成骨誘導劑的BMP包括但不限于以下BMP對應于SEQ ID NO1、SEQ ID NO2、SEQ ID NO3和SEQ ID NO4的BMP-1多核苷酸和多肽，以及成熟BMP-1多肽和編碼它的多核苷酸；對應于SEQ ID NO5和SEQ ID NO66的BMP-2多核苷酸和多肽，以及成熟BMP-2多肽和編碼它的多核苷酸；對應于SEQ ID NO7和SEQ ID NO8的BMP-3多核苷酸和多肽，以及成熟BMP-3多肽和編碼它的多核苷酸；對應于SEQ ID NO9和SEQ ID NO10的BMP-4多核苷酸和多肽，以及成熟BMP-4多肽和編碼它的多核苷酸；對應于SEQ ID NO11、SEQ ID NO12、SEQ ID NO13和SEQ ID NO14的BMP-5多核苷酸和多肽，以及成熟BMP-5多肽和編碼它的多核苷酸；對應于SEQ ID NO15、SEQ ID NO16、SEQ ID NO17和SEQ ID NO18的BMP-6多核苷酸和多肽，以及成熟BMP-6多肽和編碼它的多核苷酸；對應于SEQ ID NO19、SEQ ID NO20、SEQ ID NO21和SEQ ID NO22的BMP-7多核苷酸和多肽，以及成熟BMP-7多肽和編碼它的多核苷酸；對應于SEQ ID NO23、SEQ ID NO24、SEQ ID NO25和SEQ ID NO26的BMP-8多核苷酸和多肽，以及成熟BMP-8多肽和編碼它的多核苷酸；對應于SEQ ID NO27和SEQ ID NO28的BMP-9多核苷酸和多肽，以及成熟BMP-9多肽和編碼它的多核苷酸；
對應于SEQ ID NO29、SEQ ID NO30、SEQ ID NO31和SEQ ID NO32的BMP-10多核苷酸和多肽，以及成熟BMP-10多肽和編碼它的多核苷酸；對應于SEQ ID NO33和SEQ ID NO34的BMP-11多核苷酸和多肽，以及成熟BMP-11多肽和編碼它的多核苷酸；對應于SEQ ID NO35和SEQ ID NO36的BMP-12多核苷酸和多肽，以及成熟BMP-12多肽和編碼它的多核苷酸；對應于SEQ ID NO37和SEQ ID NO38的BMP-13多核苷酸和多肽，以及成熟BMP-13多肽和編碼它的多核苷酸；對應于SEQ ID NO39、SEQ ID NO40、SEQ ID NO41和SEQ ID NO42的BMP-15多核苷酸和多肽，以及成熟BMP-15多肽和編碼它的多核苷酸；對應于SEQ ID NO43、SEQ ID NO44、SEQ ID NO45和SEQ ID NO46的BMP-16多核苷酸和多肽，以及成熟BMP-16多肽和編碼它的多核苷酸；對應于SEQ ID NO47和SEQ ID NO48的BMP-17多核苷酸和多肽，以及成熟BMP-17多肽和編碼它的多核苷酸；和對應于SEQ ID NO49和SEQ ID NO50的BMP-18多核苷酸和多肽，以及成熟BMP-18多肽和編碼它的多核苷酸。
用作本發(fā)明成骨誘導劑的BMP包括或由以下一種或多種物質構成BMP-1；BMP-2；BMP-3；BMP-4；BMP-5；BMP-6；BMP-7；BMP-8；BMP-9；BMP-10；BMP-11；BMP-12；BMP-13；BMP-15；BMP-16；BMP-17；和BMP-18；以及一種或多種這些BMP、包括全長BMP或其片段的任意組合，，或者它們的組合，它可以是多肽形式或是編碼所有所述BMP的多肽片段的多核苷酸形式。分離的BMP成骨誘導劑可以多核苷酸、多肽或兩者組合的形式給予。
在本發(fā)明一個尤其優(yōu)選的實施方式中，分離的成骨誘導劑包括或由BMP-2多核苷酸或多肽或其成熟片段構成。
在本發(fā)明另一個實施方式中，分離的成骨誘導劑包含破骨細胞生成抑制劑，以抑制植入物植入部位周圍的骨組織被破骨細胞再吸收。
破骨細胞和破骨細胞生成抑制劑包括但不限于對應于SEQ ID NO51、SEQ ID NO52、SEQ ID NO53和SEQ ID NO54的護骨蛋白多核苷酸和多肽，以及成熟護骨蛋白多肽和編碼它的多核苷酸。護骨蛋白是TNF-受體超家族的成員，是用作骨再吸收負調節(jié)物的成骨細胞分泌的誘殺受體。這種蛋白特異性結合于其配體，即護骨蛋白配體(TNFSF11/OPGL)，它們都是破骨細胞形成的關鍵性細胞外調節(jié)物。
破骨細胞生成抑制劑還包括但不限于化合物如二膦酸鹽(bisphosphonate)、5-脂肪氧合酶抑制劑如美國專利5,534,524和6,455,541所述(其內容參考包括在此)，雜環(huán)化合物如美國專利5,658,935所述(其內容參考包括在此)，2，4-二氧代咪唑烷和咪唑烷衍生物如美國專利5,397,796和5,554,594所述(其內容參考包括在此)，磺胺衍生物如美國專利6,313,119所述(其內容參考包括在此)，和?；一衔锶缑绹鴮＠?,492,356所述(其內容參考包括在此)。
在本發(fā)明另一個實施方式中，分離的成骨誘導劑包括結締組織生長因子(“CTGF”)家族成員的一種或多種多核苷酸或多肽。CTGF是一類認為對結締組織具有生長促進活性的蛋白質。已知的CTGF家族成員包括但不限于CTGF-1、CTGF-2和CTGF-4。
可用作分離的成骨誘導劑的CTGF包括但不限于以下CTGF對應于SEQ ID NO55、SEQ ID NO56、SEQ ID NO57和SEQ ID NO58的CTGF-1多核苷酸和多肽，以及成熟CTGF-1多肽和編碼它的多核苷酸。
對應于SEQ ID NO59和SEQ ID NO60的CTGF-2多核苷酸和多肽，以及成熟CTGF-2多肽和編碼它的多核苷酸。
對應于SEQ ID NO61和SEQ ID NO62的CTGF-4多核苷酸和多肽，以及成熟CTGF-4多肽和編碼它的多核苷酸。
在本發(fā)明另一個實施方式中，分離的成骨誘導劑包括血管內皮生長因子(“VEGF”)家族成員的一種或多種多核苷酸或多肽。VEGF是一類認為對血管組織具有生長促進活性的蛋白質。已知的VEGF家族成員包括但不限于VEGF-A、VEGF-B、VEGF-C、VEGF-D和VEGF-E。
可用作成骨誘導劑的VEGF包括但不限于以下VEGF對應于SEQ ID NO63和SEQ ID NO64的VEGF-A多核苷酸和多肽，以及成熟VEGF-A多肽和編碼它的多核苷酸。
對應于SEQ ID NO65和SEQ ID NO66的VEGF-B多核苷酸和多肽，以及成熟VEGF-B多肽和編碼它的多核苷酸。
對應于SEQ ID NO67和SEQ ID NO68的VEGF-C多核苷酸和多肽，以及成熟VEGF-C多肽和編碼它的多核苷酸。
對應于SEQ ID NO69和SEQ ID NO70的VEGF-D多核苷酸和多肽，以及成熟VEGF-D多肽和編碼它的多核苷酸。
對應于SEQ ID NO71和SEQ ID NO72的VEGF-E多核苷酸和多肽，以及成熟VEGF-E多肽和編碼它的多核苷酸。
在本發(fā)明另一個實施方式中，分離的成骨誘導劑包括轉化生長因子β基因(“TGF-β”)的一種或多種多核苷酸或多肽。TGF-β是一類認為對多種組織包括結締組織具有生長促進活性的蛋白質。已知的TGF-β家族成員包括但不限于TGF-β-1、TGF-β-2和TGF-β-3。
可用作分離的成骨誘導劑的TGF-β包括但不限于以下TGF-β對應于SEQ ID NO73、SEQ ID NO74、SEQ ID NO75和SEQ ID NO76的TGF-β-1多核苷酸和多肽，以及成熟TGF-β-1多肽和編碼它的多核苷酸。
對應于SEQ ID NO77、SEQ ID NO78、SEQ ID NO79和SEQ ID NO80的TGF-β-2多核苷酸和多肽，以及成熟TGF-β-2多肽和編碼它的多核苷酸。
對應于SEQ ID NO81和SEQ ID NO82的TGF-β-3多核苷酸和多肽，以及成熟TGF-β-3多肽和編碼它的多核苷酸。
在本發(fā)明另一個實施方式中，分離的成骨誘導劑包括促進骨接合(adhesion)的多核苷酸和多肽，例如認為在骨形成中起接合分子作用的Periostin多核苷酸和多肽。
骨接合促進劑包括但不限于對應于SEQ ID NO83和SEQ ID NO84的Periostin多核苷酸和多肽，以及成熟Periostin多肽和編碼它的多核苷酸。
在本發(fā)明另一個實施方式中，分離的成骨誘導劑包括以下任一蛋白家族中的一個或多個成員骨形態(tài)發(fā)生蛋白(BMP)、結締組織生長因子(CTGF)、血管內皮生長因子(VEGF)、護骨蛋白或任何其它破骨細胞生成抑制劑、Periostin和轉化生長因子-β(TGF-β)、以及這些成骨誘導劑的任意組合。
用于制備聚合物包裹物的聚合物包括能夠形成生物學上可接受的可生物降解薄膜的任何聚合物。本發(fā)明聚合物包裹物包括一個或多個可生物降解的聚合物層，其中，所述可生物降解的聚合物層在聚合物層中任選地包含成骨誘導性制劑。在本發(fā)明的一個實施方式中，多層聚合物包裹物的制備過程如下合成含有一種或多種成骨誘導劑作為成骨誘導性制劑組分的至少兩個獨立的聚合物層；然后，例如通過將一個聚合物層鋪在另外一層或多層上合并所述至少兩個獨立的聚合物層，形成多層聚合物包裹物。任選地，使用少量可生物降解的粘固劑或其它生物相容性粘合劑作為所述至少兩個獨立的聚合物層之間的粘合劑。
在本發(fā)明另一個實施方式中，在將下一聚合物層疊加到多層聚合物包裹物上之前，將成骨誘導性制劑施加到可生物降解的聚合物層的表面上。在該實施方式中，包含的成骨誘導性制劑是聚合物包裹物的至少兩個獨立的聚合物層之間的液體層。一旦一個或多個聚合物層降解，成骨誘導性制劑從聚合物包裹物中釋放，以生物活性形式存在。
也可通過以下過程產生聚合物包裹物制備液體形式(預聚物)的一個或多個聚合物層并與成骨誘導性制劑混合，將預聚物液體施加到預成形模具中，固化或固定液體預聚物，形成預先形成貼合在矯形外科裝置外形上的預成形聚合物包裹物。在該實施方式中，在植入患者之前或同時將預成形聚合物包裹物圍繞在矯形外科裝置的外形上。
在本發(fā)明一個可選的實施方式中，通過制備各個獨立的可生物降解聚合物層來產生預成形多層聚合物包裹物，設計在植入患者之前將預成形層圍繞在矯形外科裝置的外形上。在該可選的實施方式中，將成骨誘導性制劑以液體制劑的形式施加在獨立的預成形聚合物層之間。根據多層聚合物包裹物中獨立的可生物降解聚合物外層的體內降解速率，從多層聚合物包裹物中釋放生物活性形式的成骨誘導性制劑。
本發(fā)明還涉及含有本發(fā)明成骨誘導性多核苷酸的載體、宿主細胞、以及通過重組技術制備成骨誘導性多肽。載體可以是例如噬菌體、質粒、病毒或逆轉錄病毒載體。逆轉錄病毒載體可具有復制能力或是復制缺陷的。在后一種情況下，通常只有在補償性宿主細胞中才發(fā)生病毒增殖。
多核苷酸可連接于含有可選標記的載體在宿主中增殖。通常，將質粒載體引入沉淀物如磷酸鈣沉淀物，或與帶電脂質形成復合物。若載體是病毒，可使用合適的包裝細胞株進行體外包裝，然后轉導入宿主細胞。有用的載體包括但不限于質粒、噬菌體、昆蟲和動物細胞載體、逆轉錄病毒、粘粒、以及其它單鏈和雙鏈病毒。
多核苷酸插入物應可操作地連接于合適的啟動子，例如噬菌體λPL啟動子，大腸桿菌(E.Coli)lac、trp、phoA和tac啟動子，SV40早期和晚期啟動子以及逆轉錄病毒LTR的啟動子等。其它合適的啟動子是本領域技術人員已知的。表達構建物還包括轉錄起始位點、轉錄終止位點；復制序列起點、以及轉錄區(qū)中用于翻譯的核糖體結合位點。構建物表達的轉錄物的編碼部分優(yōu)選包括開始處的翻譯起始密碼子和適當地位于待翻譯多肽末端的終止密碼子(UAA、UGA或UAG)。
表達構建物可還包含以下序列，例如增強子序列、有效RNA加工信號如剪接和聚腺苷酸化信號、提高翻譯效率的序列以及增加蛋白質分泌的序列。
制備成骨誘導劑如重組蛋白或蛋白片段的表達系統(tǒng)和方法是本領域眾所周知的。例如，采用細菌、昆蟲或哺乳動物表達系統(tǒng)來制備重組蛋白或其片段的方法是本領域眾所周知的(例如參見“分子生物技術重組DNA的原理和應用”(Molecular BiotechnologyPrinciples and Applications of Recombinant DNA)，B.R.Glick、J.Pasternak和M.M.Bendig，Genetic Engineering，7，第91-127頁(1988)，關于重組蛋白制備的討論)。
表達載體優(yōu)選包括至少一個可選擇標記。所述標記包括二氫葉酸還原酶、G418或新霉素。
序列表<110>J·C·塞爾布賽克(Serbousek，Jon)<120>體內遞送骨誘導性制劑的聚合物包合物<130>64118.000083<160>84<170>PatentIn version 3.2<210>1<211>2487<212>DNA<213>智人(Homo sapiens)<400>1gccgcttccc tcgccgccgc cccgccagca tgcccggcgt ggcccgcctg ccgctgctgc 60tcgggctgct gctgctcccg cgtcccggcc ggccgctgga cttggccgac tacacctatg120acctggcgga ggaggacgac tcggagcccc tcaactacaa agacccctgc aaggcggctg180cctttcttgg ggacattgcc ctggacgaag aggacctgag ggccttccag gtacagcagg240ctgtggatct cagacggcac acagctcgta agtcctccat caaagctgca gttccaggaa300acacttctac ccccagctgc cagagcacca acgggcagcc tcagagggga gcctgtggga360gatggagagg tagatcccgt agccggcggg cggcgacgtc ccgaccagag cgtgtgtggc420ccgatggggt catccccttt gtcattgggg gaaacttcac tggtagccag agggcagtct480tccggcaggc catgaggcac tgggagaagc acacctgtgt caccttcctg gagcgcactg540acgaggacag ctatattgtg ttcacctatc gaccttgcgg gtgctgctcc tacgtgggtc600gccgcggcgg gggcccccag gccatctcca tcggcaagaa ctgtgacaag ttcggcattg660tggtccacga gctgggccac gtcgtcggct tctggcacga acacactcgg ccagaccggg720accgccacgt ttccatcgtt cgtgagaaca tccagccagg gcaggagtat aacttcctga780agatggagcc tcaggaggtg gagtccctgg gggagaccta tgacttcgac agcatcatgc840attacgctcg gaacacattc tccaggggca tcttcctgga taccattgtc cccaagtatg900aggtgaacgg ggtgaaacct cccattggcc aaaggacacg gctcagcaag ggggacattg960cccaagcccg caagctttac aagtgcccag cctgtggaga gaccctgcaa gacagcacag 1020gcaacttctc ctcccctgaa taccccaatg gctactctgc tcacatgcac tgcgtgtggc 1080gcatctctgt cacacccggg gagaagatca tcctgaactt cacgtccctg gacctgtacc 1140gcagccgcct gtgctggtac gactatgtgg aggtccgaga tggcttctgg aggaaggcgc 1200ccctccgagg ccgcttctgc gggtccaaac tccctgagcc tatcgtctcc actgacagcc 1260gcctctgggt tgaattccgc agcagcagca attgggttgg aaagggcttc tttgcagtct 1320acgaagccat ctgcgggggt gatgtgaaaa aggactatgg ccacattcaa tcgcccaact 1380acccagacga ttaccggccc agcaaagtct gcatctggcg gatccaggtg tctgagggct 1440tccacgtggg cctcacattc cagtcctttg agattgagcg ccacgacagc tgtgcctacg 1500actatctgga ggtgcgcgac gggcacagtg agagcagcac cctcatcggg cgctactgtg 1560gctatgagaa gcctgatgac atcaagagca cgtccagccg cctctggctc aagttcgtct 1620ctgacgggtc cattaacaaa gcgggctttg ccgtcaactt tttcaaagag gtggacgagt 1680gctctcggcc caaccgcggg ggctgtgagc agcggtgcct caacaccctg ggcagctaca 1740agtgcagctg tgaccccggg tacgagctgg ccccagacaa gcgccgctgt gaggctgctt 1800gtggcggatt cctcaccaag ctcaacggct ccatcaccag cccgggctgg cccaaggagt 1860acccccccaa caagaactgc atctggcagc tggtggcccc cacccagtac cgcatctccc 1920tgcagtttga cttctttgag acagagggca atgatgtgtg caagtacgac ttcgtggagg 1980tgcgcagtgg actcacagct gactccaagc tgcatggcaa gttctgtggt tctgagaagc 2040
ccgaggtcat cacctcccag tacaacaaca tgcgcgtgga gttcaagtcc gacaacaccg 2100tgtccaaaaa gggcttcaag gcccacttct tctcagaaaa gaggccagct ctgcagcccc 2160ctcggggacg cccccaccag ctcaaattcc gagtgcagaa aagaaaccgg accccccagt 2220gaggcctgcc aggcctcccg gaccccttgt tactcaggaa cctcaccttg gacggaatgg 2280gatgggggct tcggtgccca ccaacccccc acctccactc tgccattccg gcccacctcc 2340ctctggccgg acagaactgg tgctctcttc tccccactgt gcccgtccgc ggaccgggga 2400cccttccccg tgccctaccc cctcccattt tgatggtgtc tgtgacattt cctgttgtga 2460agtaaaagag ggacccctgc gtcctgc 2487<210>2<211>730<212>PRT<213>智人(Homo sapiens)<400>2Met Pro Gly Val Ala Arg Leu Pro Leu Leu Leu Gly Leu Leu Leu Leu1 5 10 15Pro Arg Pro Gly Arg Pro Leu Asp Leu Ala Asp Tyr Thr Tyr Asp Leu20 25 30Ala Glu Glu Asp Asp Ser Glu Pro Leu Asn Tyr Lys Asp Pro Cys Lys35 40 45Ala Ala Ala Phe Leu Gly Asp Ile Ala Leu Asp Glu Glu Asp Leu Arg50 55 60Ala Phe Gln Val Gln Gln Ala Val Asp Leu Arg Arg His Thr Ala Arg65 70 75 80Lys Ser Ser Ile Lys Ala Ala Val Pro Gly Asn Thr Ser Thr Pro Ser85 90 95Cys Gln Ser Thr Asn Gly Gln Pro Gln Arg Gly Ala Cys Gly Arg Trp100 105 110Arg Gly Arg Ser Arg Ser Arg Arg Ala Ala Thr Ser Arg Pro Glu Arg115 120 125Val Trp Pro Asp Gly Val Ile Pro Phe Val Ile Gly Gly Asn Phe Thr130 135 140Gly Ser Gln Arg Ala Val Phe Arg Gln Ala Met Arg His Trp Glu Lys145 150 155 160His Thr Cys Val Thr Phe Leu Glu Arg Thr Asp Glu Asp Ser Tyr Ile165 170 175Val Phe Thr Tyr Arg Pro Cys Gly Cys Cys Ser Tyr Val Gly Arg Arg180 185 190Gly Gly Gly Pro Gln Ala Ile Ser Ile Gly Lys Asn Cys Asp Lys Phe
195 200 205Gly Ile Val Val His Glu Leu Gly His Val Val Gly Phe Trp His Glu210 215 220His Thr Arg Pro Asp Arg Asp Arg His Val Ser Ile Val Arg Glu Asn225 230 235 240Ile Gln Pro Gly Gln Glu Tyr Asn Phe Leu Lys Met Glu Pro Gln Glu245 250 255Val Glu Ser Leu Gly Glu Thr Tyr Asp Phe Asp Ser Ile Met His Tyr260 265 270Ala Arg Asn Thr Phe Ser Arg Gly Ile Phe Leu Asp Thr Ile Val Pro275 280 285Lys Tyr Glu Val Asn Gly Val Lys Pro Pro Ile Gly Gln Arg Thr Arg290 295 300Leu Ser Lys Gly Asp Ile Ala Gln Ala Arg Lys Leu Tyr Lys Cys Pro305 310 315 320Ala Cys Gly Glu Thr Leu Gln Asp Ser Thr Gly Asn Phe Ser Ser Pro325 330 335Glu Tyr Pro Asn Gly Tyr Ser Ala His Met His Cys Val Trp Arg Ile340 345 350Ser Val Thr Pro Gly Glu Lys Ile Ile Leu Asn Phe Thr Ser Leu Asp355 360 365Leu Tyr Arg Ser Arg Leu Cys Trp Tyr Asp Tyr Val Glu Val Arg Asp370 375 380Gly Phe Trp Arg Lys Ala Pro Leu Arg Gly Arg Phe Cys Gly Ser Lys385 390 395 400Leu Pro Glu Pro Ile Val Ser Thr Asp Ser Arg Leu Trp Val Glu Phe405 410 415Arg Ser Ser Ser Asn Trp Val Gly Lys Gly Phe Phe Ala Val Tyr Glu420 425 430Ala Ile Cys Gly Gly Asp Val Lys Lys Asp Tyr Gly His Ile Gln Ser435 440 445Pro Asn Tyr Pro Asp Asp Tyr Arg Pro Ser Lys Val Cys Ile Trp Arg450 455 460Ile Gln Val Ser Glu Gly Phe His Val Gly Leu Thr Phe Gln Ser Phe465 470 475 480
Glu Ile Glu Arg His Asp Ser Cys Ala Tyr Asp Tyr Leu Glu Val Arg485 490 495Asp Gly His Ser Glu Ser Ser Thr Leu Ile Gly Arg Tyr Cys Gly Tyr500 505 510Glu Lys Pro Asp Asp Ile Lys Ser Thr Ser Ser Arg Leu Trp Leu Lys515 520 525Phe Val Ser Asp Gly Ser Ile Asn Lys Ala Gly Phe Ala Val Asn Phe530 535 540Phe Lys Glu Val Asp Glu Cys Ser Arg Pro Asn Arg Gly Gly Cys Glu545 550 555 560Gln Arg Cys Leu Asn Thr Leu Gly Ser Tyr Lys Cys Ser Cys Asp Pro565 570 575Gly Tyr Glu Leu Ala Pro Asp Lys Arg Arg Cys Glu Ala Ala Cys Gly580 585 590Gly Phe Leu Thr Lys Leu Asn Gly Ser Ile Thr Ser Pro Gly Trp Pro595 600 605Lys Glu Tyr Pro Pro Asn Lys Asn Cys Ile Trp Gln Leu Val Ala Pro610 615 620Thr Gln Tyr Arg Ile Ser Leu Gln Phe Asp Phe Phe Glu Thr Glu Gly625 630 635 640Asn Asp Val Cys Lys Tyr Asp Phe Val Glu Val Arg Ser Gly Leu Thr645 650 655Ala Asp Ser Lys Leu His Gly Lys Phe Cys Gly Ser Glu Lys Pro Glu660 665 670Val Ile Thr Ser Gln Tyr Asn Asn Met Arg Val Glu Phe Lys Ser Asp675 680 685Asn Thr Val Ser Lys Lys Gly Phe Lys Ala His Phe Phe Ser Glu Lys690 695 700Arg Pro Ala Leu Gln Pro Pro Arg Gly Arg Pro His Gln Leu Lys Phe705 710 715 720Arg Val Gln Lys Arg Asn Arg Thr Pro Gln725 730<210>3<211>1821
<212>DNA<213>智人(Homo sapiens)<400>3tcccgaccag agcgtgtgtg gcccgatggg gtcatcccct ttgtcattgg gggaaacttc 60actggtagcc agagggcagt cttccggcag gccatgaggc actgggagaa gcacacctgt120gtcaccttcc tggagcgcac tgacgaggac agctatattg tgttcaccta tcgaccttgc180gggtgctgct cctacgtggg tcgccgcggc gggggccccc aggccatctc catcggcaag240aactgtgaca agttcggcat tgtggtccac gagctgggcc acgtcgtcgg cttctggcac300gaacacactc ggccagaccg ggaccgccac gtttccatcg ttcgtgagaa catccagcca360gggcaggagt ataacttcct gaagatggag cctcaggagg tggagtccct gggggagacc420tatgacttcg acagcatcat gcattacgct cggaacacat tctccagggg catcttcctg480gataccattg tccccaagta tgaggtgaac ggggtgaaac ctcccattgg ccaaaggaca540cggctcagca agggggacat tgcccaagcc cgcaagcttt acaagtgccc agcctgtgga600gagaccctgc aagacagcac aggcaacttc tcctcccctg aataccccaa tggctactct660gctcacatgc actgcgtgtg gcgcatctct gtcacacccg gggagaagat catcctgaac720ttcacgtccc tggacctgta ccgcagccgc ctgtgctggt acgactatgt ggaggtccga780gatggcttct ggaggaaggc gcccctccga ggccgcttct gcgggtccaa actccctgag840cctatcgtct ccactgacag ccgcctctgg gttgaattcc gcagcagcag caattgggtt900ggaaagggct tctttgcagt ctacgaagcc atctgcgggg gtgatgtgaa aaaggactat960ggccacattc aatcgcccaa ctacccagac gattaccggc ccagcaaagt ctgcatctgg 1020cggatccagg tgtctgaggg cttccacgtg ggcctcacat tccagtcctt tgagattgag 1080cgccacgaca gctgtgccta cgactatctg gaggtgcgcg acgggcacag tgagagcagc 1140accctcatcg ggcgctactg tggctatgag aagcctgatg acatcaagag cacgtccagc 1200cgcctctggc tcaagttcgt ctctgacggg tccattaaca aagcgggctt tgccgtcaac 1260tttttcaaag aggtggacga gtgctctcgg cccaaccgcg ggggctgtga gcagcggtgc 1320ctcaacaccc tgggcagcta caagtgcagc tgtgaccccg ggtacgagct ggccccagac 1380aagcgccgct gtgaggctgc ttgtggcgga ttcctcacca agctcaacgg ctccatcacc 1440agcccgggct ggcccaagga gtaccccccc aacaagaact gcatctggca gctggtggcc 1500cccacccagt accgcatctc cctgcagttt gacttctttg agacagaggg caatgatgtg 1560tgcaagtacg acttcgtgga ggtgcgcagt ggactcacag ctgactccaa gctgcatggc 1620aagttctgtg gttctgagaa gcccgaggtc atcacctccc agtacaacaa catgcgcgtg 1680gagttcaagt ccgacaacac cgtgtccaaa aagggcttca aggcccactt cttctcagaa 1740aagaggccag ctctgcagcc ccctcgggga cgcccccacc agctcaaatt ccgagtgcag 1800aaaagaaacc ggacccccca g 1821<210>4<21l>610<212>PRT<213>智人(Homo sapiens)<400>4Ala Ala Thr Ser Arg Pro Glu Arg Val Trp Pro Asp Gly Val Ile Pro1 5 10 15Phe Val Ile Gly Gly Asn Phe Thr Gly Ser Gln Arg Ala Val Phe Arg20 25 30Gln Ala Met Arg His Trp Glu Lys His Thr Cys Val Thr Phe Leu Glu35 40 45
Arg Thr Asp Glu Asp Ser Tyr Ile Val Phe Thr Tyr Arg Pro Cys Gly50 55 60Cys Cys Ser Tyr Val Gly Arg Arg Gly Gly Gly Pro Gln Ala Ile Ser65 70 75 80Ile Gly Lys Asn Cys Asp Lys Phe Gly Ile Val Val His Glu Leu Gly85 90 95His Val Val Gly Phe Trp His Glu His Thr Arg Pro Asp Arg Asp Arg100 105 110His Val Ser Ile Val Arg Glu Asn Ile Gln Pro Gly Gln Glu Tyr Asn115 120 125Phe Leu Lys Met Glu Pro Gln Glu Val Glu Ser Leu Gly Glu Thr Tyr130 135 140Asp Phe Asp Ser Ile Met His Tyr Ala Arg Asn Thr Phe Ser Arg Gly145 150 155 160Ile Phe Leu Asp Thr Ile Val Pro Lys Tyr Glu Val Asn Gly Val Lys165 170 175Pro Pro Ile Gly Gln Arg Thr Arg Leu Ser Lys Gly Asp Ile Ala Gln180 185 190Ala Arg Lys Leu Tyr Lys Cys Pro Ala Cys Gly Glu Thr Leu Gln Asp195 200 205Ser Thr Gly Asn Phe Ser Ser Pro Glu Tyr Pro Asn Gly Tyr Ser Ala210 215 220His Met His Cys Val Trp Arg Ile Ser Val Thr Pro Gly Glu Lys Ile225 230 235 240Ile Leu Asn Phe Thr Ser Leu Asp Leu Tyr Arg Ser Arg Leu Cys Trp245 250 255Tyr Asp Tyr Val Glu Val Arg Asp Gly Phe Trp Arg Lys Ala Pro Leu260 265 270Arg Gly Arg Phe Cys Gly Ser Lys Leu Pro Glu Pro Ile Val Ser Thr275 280 285Asp Ser Arg Leu Trp Val Glu Phe Arg Ser Ser Ser Asn Trp Val Gly290 295 300Lys Gly Phe Phe Ala Val Tyr Glu Ala Ile Cys Gly Gly Asp Val Lys305 310 315 320Lys Asp Tyr Gly His Ile Gln Ser Pro Asn Tyr Pro Asp Asp Tyr Arg
325 330 335Pro Ser Lys Val Cys Ile Trp Arg Ile Gln Val Ser Glu Gly Phe His340 345 350Val Gly Leu Thr Phe Gln Ser Phe Glu Ile Glu Arg His Asp Ser Cys355 360 365Ala Tyr Asp Tyr Leu Glu Val Arg Asp Gly His Ser Glu Ser Ser Thr370 375 380Leu Ile Gly Arg Tyr Cys Gly Tyr Glu Lys Pro Asp Asp Ile Lys Ser385 390 395 400Thr Ser Ser Arg Leu Trp Leu Lys Phe Val Ser Asp Gly Ser Ile Asn405 410 415Lys Ala Gly Phe Ala Val Asn Phe Phe Lys Glu Val Asp Glu Cys Ser420 425 430Arg Pro Asn Arg Gly Gly Cys Glu Gln Arg Cys Leu Asn Thr Leu Gly435 440 445Ser Tyr Lys Cys Ser Cys Asp Pro Gly Tyr Glu Leu Ala Pro Asp Lys450 455 460Arg Arg Cys Glu Ala Ala Cys Gly Gly Phe Leu Thr Lys Leu Asn Gly465 470 475 480Ser Ile Thr Ser Pro Gly Trp Pro Lys Glu Tyr Pro Pro Asn Lys Asn485 490 495Cys Ile Trp Gln Leu Val Ala Pro Thr Gln Tyr Arg Ile Ser Leu Gln500 505 510Phe Asp Phe Phe Glu Thr Glu Gly Asn Asp Val Cys Lys Tyr Asp Phe515 520 525Val Glu Val Arg Ser Gly Leu Thr Ala Asp Ser Lys Leu His Gly Lys530 535 540Phe Cys Gly Ser Glu Lys Pro Glu Val Ile Thr Ser Gln Tyr Asn Asn545 550 555 560Met Arg Val Glu Phe Lys Ser Asp Asn Thr Val Ser Lys Lys Gly Phe565 570 575Lys Ala His Phe Phe Ser Glu Lys Arg Pro Ala Leu Gln Pro Pro Arg580 585 590Gly Arg Pro His Gln Leu Lys Phe Arg Val Gln Lys Arg Asn Arg Thr595 600 605
Pro Gln610<210>5<211>1547<212>DNA<213>智人(Homo sapiens)<400>5ggggacttct tgaacttgca gggagaataa cttgcgcacc ccactttgcg ccggtgcctt 60tgccccagcg gagcctgctt cgccatctcc gagccccacc gcccctccac tcctcggcct120tgcccgacac tgagacgctg ttcccagcgt gaaaagagag actgcgcggc cggcacccgg180gagaaggagg aggcaaagaa aaggaacgga cattcggtcc ttgcgccagg tcctttgacc240agagtttttc catgtggacg ctctttcaat ggacgtgtcc ccgcgtgctt cttagacgga300ctgcggtctc ctaaaggtcg accatggtgg ccgggacccg ctgtcttcta gcgttgctgc360ttccccaggt cctcctgggc ggcgcggctg gcctcgttcc ggagctgggc cgcaggaagt420tcgcggcggc gtcgtcgggc cgcccctcat cccagccctc tgacgaggtc ctgagcgagt480tcgagttgcg gctgctcagc atgttcggcc tgaaacagag acccaccccc agcagggacg540ccgtggtgcc cccctacatg ctagacctgt atcgcaggca ctcaggtcag ccgggctcac600ccgccccaga ccaccggttg gagagggcag ccagccgagc caacactgtg cgcagcttcc660accatgaaga atctttggaa gaactaccag aaacgagtgg gaaaacaacc cggagattct720tctttaattt aagttctatc cccacggagg agtttatcac ctcagcagag cttcaggttt780tccgagaaca gatgcaagat gctttaggaa acaatagcag tttccatcac cgaattaata840tttatgaaat cataaaacct gcaacagcca actcgaaatt ccccgtgacc agacttttgg900acaccaggtt ggtgaatcag aatgcaagca ggtgggaaag ttttgatgtc acccccgctg960tgatgcggtg gactgcacag ggacacgcca accatggatt cgtggtggaa gtggcccact 1020tggaggagaa acaaggtgtc tccaagagac atgttaggat aagcaggtct ttgcaccaag 1080atgaacacag ctggtcacag ataaggccat tgctagtaac ttttggccat gatggaaaag 1140ggcatcctct ccacaaaaga gaaaaacgtc aagccaaaca caaacagcgg aaacgcctta 1200agtccagctg taagagacac cctttgtacg tggacttcag tgacgtgggg tggaatgact 1260ggattgtggc tcccccgggg tatcacgcct tttactgcca cggagaatgc ccttttcctc 1320tggctgatca tctgaactcc actaatcatg ccattgttca gacgttggtc aactctgtta 1380actctaagat tcctaaggca tgctgtgtcc cgacagaact cagtgctatc tcgatgctgt 1440accttgacga gaatgaaaag gttgtattaa agaactatca ggacatggtt gtggagggtt 1500gtgggtgtcg ctagtacagc aaaattaaat acataaatat atatata 1547<210>6<211>396<212>PRT<213>智人(Homo sapiens)<400>6Met Val Ala Gly Thr Arg Cys Leu Leu Ala Leu Leu Leu Pro Gln Val1 5 10 15Leu Leu Gly Gly Ala Ala Gly Leu Val Pro Glu Leu Gly Arg Arg Lys20 25 30Phe Ala Ala Ala Ser Ser Gly Arg Pro Ser Ser Gln Pro Ser Asp Glu35 40 45
Val Leu Ser Glu Phe Glu Leu Arg Leu Leu Ser Met Phe Gly Leu Lys50 55 60Gln Arg Pro Thr Pro Ser Arg Asp Ala Val Val Pro Pro Tyr Met Leu65 70 75 80Asp Leu Tyr Arg Arg His Ser Gly Gln Pro Gly Ser Pro Ala Pro Asp85 90 95His Arg Leu Glu Arg Ala Ala Ser Arg Ala Asn Thr Val Arg Ser Phe100 105 110His His Glu Glu Ser Leu Glu Glu Leu Pro Glu Thr Ser Gly Lys Thr115 120 125Thr Arg Arg Phe Phe Phe Asn Leu Ser Ser Ile Pro Thr Glu Glu Phe130 135 140Ile Thr Ser Ala Glu Leu Gln Val Phe Arg Glu Gln Met Gln Asp Ala145 150 155 160Leu Gly Asn Asn Ser Ser Phe His His Arg Ile Asn Ile Tyr Glu Ile165 170 175Ile Lys Pro Ala Thr Ala Asn Ser Lys Phe Pro Val Thr Arg Leu Leu180 185 190Asp Thr Arg Leu Val Asn Gln Asn Ala Ser Arg Trp Glu Ser Phe Asp195 200 205Val Thr Pro Ala Val Met Arg Trp Thr Ala Gln Gly His Ala Asn His210 215 220Gly Phe Val Val Glu Val Ala His Leu Glu Glu Lys Gln Gly Val Ser225 230 235 240Lys Arg His Val Arg Ile Ser Arg Ser Leu His Gln Asp Glu His Ser245 250 255Trp Ser Gln Ile Arg Pro Leu Leu Val Thr Phe Gly His Asp Gly Lys260 265 270Gly His Pro Leu His Lys Arg Glu Lys Arg Gln Ala Lys His Lys Gln275 280 285Arg Lys Arg Leu Lys Ser Ser Cys Lys Arg His Pro Leu Tyr Val Asp290 295 300Phe Ser Asp Val Gly Trp Asn Asp Trp Ile Val Ala Pro Pro Gly Tyr305 310 315 320
His Ala Phe Tyr Cys His Gly Glu Cys Pro Phe Pro Leu Ala Asp His325 330 335Leu Asn Ser Thr Asn His Ala Ile Val Gln Thr Leu Val Asn Ser Val340 345 350Asn Ser Lys Ile Pro Lys Ala Cys Cys Val Pro Thr Glu Leu Ser Ala355 360 365Ile Ser Met Leu Tyr Leu Asp Glu Asn Glu Lys Val Val Leu Lys Asn370 375 380Tyr Gln Asp Met Val Val Glu Gly Cys Gly Cys Arg385 390 395<210>7<211>1794<212>DNA<213>智人(Homo sapiens)<400>7agatcttgaa aacacccggg ccacacacgc cgcgacccac agctctttct cagcgttgga 60gtggagacgg cgcccgcagc gccctgcgcg ggtgaggtcc gcgcagctgc tggggaagag120cccacctgtc aggctgcgct gggtcagcgc agcaagtggg gctggccgct atctcgctgc180acccggccgc gtcccgggct ccgtgcgccc tcgccccagc tggtttggag ttcaaccctc240ggctccgccg ccggctcctt gcgccttcgg agtgtcccgc agcgacgccg ggagccgacg300cgccgcgcgg gtacctagcc atggctgggg cgagcaggct gctgtttctg tggctgggct360gcttctgcgt gagcctggcg cagggagaga gaccgaagcc acctttcccg gagctccgca420aagctgtgcc aggtgaccgc acggcaggtg ctggcccgga ctccgagctg gagccgcaag480acaaggtctc tgaacacatg ctgcggctct atgacaggta cagcacggtc caggcggccc540ggacaccggg ctccctggag ggaggctcgg agccctggcg ccctcggctc ctgcgcgaag600gcaacacggt tcgcagcttt cgggcggcag cagcagaaac tcttgaaaga aaaggactgt660atatcttcaa tctgacatcg ctaaccaagt ctgaaaacat tttgtctgcc acactgtatt720tctgtattgg agagctagga aacatcagcc tgagttgtcc agtgtctgga ggatgctccc780atcatgctca gaggaaacac attcagattg atctttctgc atggaccctc aaattcagca840gaaaccaaag tcaactcctt ggccatctgt cagtggatat ggccaaatct catcgagata900ttatgtcctg gctgtctaaa gatatcactc aattcttgag gaaggccaaa gaaaaagaag960agttcctcat aggatttaac attacgtcca agggacgcca gctgccaaag aggaggttac 1020cttttccaga gccttatatc ttggtatatg ccaatgatgc cgccatttct gagccagaaa 1080gtgtggtatc aagcttacag ggacaccgga attttcccac tggaactgtt cccaaatggg 1140atagccacat cagagctgcc ctttccattg agcggaggaa gaagcgctct actgggctct 1200tgctgcctct gcagaacaac gagcttcctg gggcagaata ccagtataaa aaggatgagg 1260tgtgggagga gagaaagcct tacaagaccc ttcaggctca ggcccctgaa aagagtaaga 1320ataaaaagaa acagagaaag gggcctcatc ggaagagcca gaggctccaa tttgatgagc 1380agaccctgaa aaaggcaagg agaaagcagt ggattgaacc tcggaattgc gccaggagat 1440acctcaaggt agactttgca gatattggct ggagtgaatg gattatctcc cccaagtcct 1500ttgatgccta ttattgctct ggagcatgcc agttccccat gccaaagtct ttgaagccat 1560caaatcatgc taccatccag agtatagtga gagctgtggg ggtcgttcct gggattcctg 1620agccttgctg tgtaccagaa aagatgtcct cactcagtat tttattcttt gatgaaaata 1680agaatgtagt gcttaaagta taccctaaca tgacagtaga gtcttgcgct tgcagataac 1740ctggcaaaga actcatttga atgcttaatt caatctctag agtcgacgga attc 1794
<210>8<211>472<212>PRT<213>智人(Homo sapiens)<400>8Met Ala Gly Ala Ser Arg Leu Leu Phe Leu Trp Leu Gly Cys Phe Cys1 5 10 15Val Ser Leu Ala Gln Gly Glu Arg Pro Lys Pro Pro Phe Pro Glu Leu20 25 30Arg Lys Ala Val Pro Gly Asp Arg Thr Ala Gly Ala Gly Pro Asp Ser35 40 45Glu Leu Glu Pro Gln Asp Lys Val Ser Glu His Met Leu Arg Leu Tyr50 55 60Asp Arg Tyr Ser Thr Val Gln Ala Ala Arg Thr Pro Gly Ser Leu Glu65 70 75 80Gly Gly Ser Glu Pro Trp Arg Pro Arg Leu Leu Arg Glu Gly Asn Thr85 90 95Val Arg Ser Phe Arg Ala Ala Ala Ala Glu Thr Leu Glu Arg Lys Gly100 105 110Leu Tyr Ile Phe Asn Leu Thr Ser Leu Thr Lys Ser Glu Asn Ile Leu115 120 125Ser Ala Thr Leu Tyr Phe Cys Ile Gly Glu Leu Gly Asn Ile Ser Leu130 135 140Ser Cys Pro Val Ser Gly Gly Cys Ser His His Ala Gln Arg Lys His145 150 155 160Ile Gln Ile Asp Leu Ser Ala Trp Thr Leu Lys Phe Ser Arg Asn Gln165 170 175Ser Gln Leu Leu Gly His Leu Ser Val Asp Met Ala Lys Ser His Arg180 185 190Asp Ile Met Ser Trp Leu Ser Lys Asp Ile Thr Gln Phe Leu Arg Lys195 200 205Ala Lys Glu Lys Glu Glu Phe Leu Ile Gly Phe Asn Ile Thr Ser Lys210 215 220Gly Arg Gln Leu Pro Lys Arg Arg Leu Pro Phe Pro Glu Pro Tyr Ile225 230 235 240Leu Val Tyr Ala Asn Asp Ala Ala Ile Ser Glu Pro Glu Ser Val Val
245 250 255Ser Ser Leu Gln Gly His Arg Asn Phe Pro Thr Gly Thr Val Pro Lys260 265 270Trp Asp Ser His Ile Arg Ala Ala Leu Ser Ile Glu Arg Arg Lys Lys275 280 285Arg Ser Thr Gly Leu Leu Leu Pro Leu Gln Asn Asn Glu Leu Pro Gly290 295 300Ala Glu Tyr Gln Tyr Lys Lys Asp Glu Val Trp Glu Glu Arg Lys Pro305 310 315 320Tyr Lys Thr Leu Gln Ala Gln Ala Pro Glu Lys Ser Lys Asn Lys Lys325 330 335Lys Gln Arg Lys Gly Pro His Arg Lys Ser Gln Arg Leu Gln Phe Asp340 345 350Glu Gln Thr Leu Lys Lys Ala Arg Arg Lys Gln Trp Ile Glu Pro Arg355 360 365Asn Cys Ala Arg Arg Tyr Leu Lys Val Asp Phe Ala Asp Ile Gly Trp370 375 380Ser Glu Trp Ile Ile Ser Pro Lys Ser Phe Asp Ala Tyr Tyr Cys Ser385 390 395 400Gly Ala Cys Gln Phe Pro Met Pro Lys Ser Leu Lys Pro Ser Asn His405 410 415Ala Thr Ile Gln Ser Ile Val Arg Ala Val Gly Val Val Pro Gly Ile420 425 430Pro Glu Pro Cys Cys Val Pro Glu Lys Met Ser Ser Leu Ser Ile Leu435 440 445Phe Phe Asp Glu Asn Lys Asn Val Val Leu Lys Val Tyr Pro Asn Met450 455 460Thr Val Glu Ser Cys Ala Cys Arg465 470<210>9<211>1999<212>DNA<213>智人(Homo sapiens)<400>9gagggagggg ccgccgggga agaggaggag gaaggaaaga aagaaagcga gggagggaaa 60gaggaggaag gaagatgcga gaaggcagag gaggagggag ggagggaagg agcgcggagc120
ccggcccgga agctaggtga gtgtggcatc cgagctgagg gacgcgagcc tgagacgccg 180ctgctgctcc ggctgagtat ctagcttgtc tccccgatgg gattcccgtc caagctatct 240cgagcctgca gcgccacagt ccccggccct cgcccaggtt cactgcaacc gttcagaggt 300ccccaggagc tgctgctggc gagcccgcta ctgcagggac ctatggagcc attccgtagt 360gccatcccga gcaacgcact gctgcagctt ccctgagcct ttccagcaag tttgttcaag 420attggctgtc aagaatcatg gactgttatt atatgccttg ttttctgtca agacaccatg 480attcctggta accgaatgct gatggtcgtt ttattatgcc aagtcctgct aggaggcgcg 540agccatgcta gtttgatacc tgagacgggg aagaaaaaag tcgccgagat tcagggccac 600gcgggaggac gccgctcagg gcagagccat gagctcctgc gggacttcga ggcgacactt 660ctgcagatgt ttgggctgcg ccgccgcccg cagcctagca agagtgccgt cattccggac 720tacatgcggg atctttaccg gcttcagtct ggggaggagg aggaagagca gatccacagc 780actggtcttg agtatcctga gcgcccggcc agccgggcca acaccgtgag gagcttccac 840cacgaagaac atctggagaa catcccaggg accagtgaaa actctgcttt tcgtttcctc 900tttaacctca gcagcatccc tgagaacgag gcgatctcct ctgcagagct tcggctcttc 960cgggagcagg tggaccaggg ccctgattgg gaaaggggct tccaccgtat aaacatttat 1020gaggttatga agcccccagc agaagtggtg cctgggcacc tcatcacacg actactggac 1080acgagactgg tccaccacaa tgtgacacgg tgggaaactt ttgatgtgag ccctgcggtc 1140cttcgctgga cccgggagaa gcagccaaac tatgggctag ccattgaggt gactcacctc 1200catcagactc ggacccacca gggccagcat gtcaggatta gccgatcgtt acctcaaggg 1260agtgggaatt gggcccagct ccggcccctc ctggtcacct ttggccatga tggccggggc 1320catgccttga cccgacgccg gagggccaag cgtagcccta agcatcactc acagcgggcc 1380aggaagaaga ataagaactg ccggcgccac tcgctctatg tggacttcag cgatgtgggc 1440tggaatgact ggattgtggc cccaccaggc taccaggcct tctactgcca tggggactgc 1500ccctttccac tggctgacca cctcaactca accaaccatg ccattgtgca gaccctggtc 1560aattctgtca attccagtat ccccaaagcc tgttgtgtgc ccactgaact gagtgccatc 1620tccatgctgt acctggatga gtatgataag gtggtactga aaaattatca ggagatggta 1680gtagagggat gtgggtgccg ctgagatcag gcagtccttg aggatagaca gatatacaca 1740ccacacacac acaccacata caccacacac acacgttccc atccactcac ccacacacta 1800cacagactgc ttccttatag ctggactttt atttaaaaaa aaaaaaaaaa aaatggaaaa 1860aatccctaaa cattcacctt gaccttattt atgactttac gtgcaaatgt tttgaccata 1920ttgatcatat attttgacaa aatatattta taactacgta ttaaaagaaa aaaataaaat 1980gagtcattat tttaaaggt 1999<210>10<211>408<212>PRT<213>智人(Homo sapiens)<400>10Met Ile Pro Gly Asn Arg Met Leu Met Val Val Leu Leu Cys Gln Val1 5 10 15Leu Leu Gly Gly Ala Ser His Ala Ser Leu Ile Pro Glu Thr Gly Lys20 25 30Lys Lys Val Ala Glu Ile Gln Gly His Ala Gly Gly Arg Arg Ser Gly35 40 45Gln Ser His Glu Leu Leu Arg Asp Phe Glu Ala Thr Leu Leu Gln Met50 55 60Phe Gly Leu Arg Arg Arg Pro Gln Pro Ser Lys Ser Ala Val Ile Pro
65 70 75 80Asp Tyr Met Arg Asp Leu Tyr Arg Leu Gln Ser Gly Glu Glu Glu Glu85 90 95Glu Gln Ile His Ser Thr Gly Leu Glu Tyr Pro Glu Arg Pro Ala Ser100 105 110Arg Ala Asn Thr Val Arg Ser Phe His His Glu Glu His Leu Glu Asn115 120 125Ile Pro Gly Thr Ser Glu Asn Ser Ala Phe Arg Phe Leu Phe Asn Leu130 135 140Ser Ser Ile Pro Glu Asn Glu Ala Ile Ser Ser Ala Glu Leu Arg Leu145 150 155 160Phe Arg Glu Gln Val Asp Gln Gly Pro Asp Trp Glu Arg Gly Phe His165 170 175Arg Ile Asn Ile Tyr Glu Val Met Lys Pro Pro Ala Glu Val Val Pro180 185 190Gly His Leu Ile Thr Arg Leu Leu Asp Thr Arg Leu Val His His Asn195 200 205Val Thr Arg Trp Glu Thr Phe Asp Val Ser Pro Ala Val Leu Arg Trp210 215 220Thr Arg Glu Lys Gln Pro Asn Tyr Gly Leu Ala Ile Glu Val Thr His225 230 235 240Leu His Gln Thr Arg Thr His Gln Gly Gln His Val Arg Ile Ser Arg245 250 255Ser Leu Pro Gln Gly Ser Gly Asn Trp Ala Gln Leu Arg Pro Leu Leu260 265 270Val Thr Phe Gly His Asp Gly Arg Gly His Ala Leu Thr Arg Arg Arg275 280 285Arg Ala Lys Arg Ser Pro Lys His His Ser Gln Arg Ala Arg Lys Lys290 295 300Asn Lys Asn Cys Arg Arg His Ser Leu Tyr Val Asp Phe Ser Asp Val305 310 315 320Gly Trp Asn Asp Trp Ile Val Ala Pro Pro Gly Tyr Gln Ala Phe Tyr325 330 335Cys His Gly Asp Cys Pro Phe Pro Leu Ala Asp His Leu Asn Ser Thr340 345 350
Asn His Ala Ile Val Gln Thr Leu Val Asn Ser Val Asn Ser Ser Ile355 360 365Pro Lys Ala Cys Cys Val Pro Thr Glu Leu Ser Ala Ile Ser Met Leu370 375 380Tyr Leu Asp Glu Tyr Asp Lys Val Val Leu Lys Asn Tyr Gln Glu Met385 390 395 400Val Val Glu Gly Cys Gly Cys Arg405<210>11<211>2207<212>DNA<213>智人(Homo sapiens)<400>11ctcttgaaga gggctggtat atttgtgcct gctggaggtg gaattaacag taagaaggag 60aaagggattg aatggactta caggaaggat ttcaagtaaa ttcagggaaa cacatttact120tgaatagtac aacctagagt attattttac actaagacga cacaaaagat gttaaagtta180tcaccaagct gccggacaga tatatattcc aacaccaagg tgcagatcag catagatctg240tgattcagaa atcaggattt gttttggaaa gagctcaagg gttgagaaga actcaaaagc300aagtgaagat tactttggga actacagttt atcagaagat caacttttgc taattcaaat360accaaaggcc tgattatcat aaattcatat aggaatgcat aggtcatctg atcaaataat420attagccgtc ttctgctaca tcaatgcagc aaaaactctt aacaactgtg gataattgga480aatctgagtt tcagctttct tagaaataac tactcttgac atattccaaa atatttaaaa540taggacagga aaatcggtga ggatgttgtg ctcagaaatg tcactgtcat gaaaaatagg600taaatttgtt ttttcagcta ctgggaaact gtacctccta gaaccttagg tttttttttt660ttttaagagg acaagaagga ctaaaaatat caacttttgc ttttggacaa aaatgcatct720gactgtattt ttacttaagg gtattgtggg tttcctctgg agctgctggg ttctagtggg780ttatgcaaaa ggaggtttgg gagacaatca tgttcactcc agttttattt atagaagact840acggaaccac gaaagacggg aaatacaaag ggaaattctc tctatcttgg gtttgcctca900cagacccaga ccattttcac ctggaaaaca agcgtcctct gcacctctct ttatgctgga960tctctacaat gccatgacca atgaagaaaa tcctgaagag tcggagtact cagtaagggc 1020atccttggca gaagagacca gaggggcaag aaagggatac ccagcctctc ccaatgggta 1080tcctcgtcgc atacagttat ctcggacgac tcctctgacc acccagagtc ctcctctagc 1140cagcctccat gataccaact ttctgaatga tgctgacatg gtcatgagct ttgtcaactt 1200agttgaaaga gacaaggatt tttctcacca gcgaaggcat tacaaagaat ttcgatttga 1260tcttacccaa attcctcatg gagaggcagt gacagcagct gaattccgga tatacaagga 1320ccggagcaac aaccgatttg aaaatgaaac aattaagatt agcatatatc aaatcatcaa 1380ggaatacaca aatagggatg cagatctgtt cttgttagac acaagaaagg cccaagcttt 1440agatgtgggt tggcttgtct ttgatatcac tgtgaccagc aatcattggg tgattaatcc 1500ccagaataat ttgggcttac agctctgtgc agaaacaggg gatggacgca gtatcaacgt 1560aaaatctgct ggtcttgtgg gaagacaggg acctcagtca aaacaaccat tcatggtggc 1620cttcttcaag gcgagtgagg tacttcttcg atccgtgaga gcagccaaca aacgaaaaaa 1680tcaaaaccgc aataaatcca gctctcatca ggactcctcc agaatgtcca gtgttggaga 1740ttataacaca agtgagcaaa aacaagcctg taagaagcac gaactctatg tgagcttccg 1800ggatctggga tggcaggact ggattatagc accagaagga tacgctgcat tttattgtga 1860tggagaatgt tcttttccac ttaacgccca tatgaatgcc accaaccacg ctatagttca 1920gactctggtt catctgatgt ttcctgacca cgtaccaaag ccttgttgtg ctccaaccaa 1980
attaaatgcc atctctgttc tgtactttga tgacagctcc aatgtcattt tgaaaaaata 2040tagaaatatg gtagtacgct catgtggctg ccactaatat taaataatat tgataataac 2100aaaaagatct gtattaaggt ttatggctgc aataaaaagc atactttcag acaaacgggg 2160aatttcctaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaa2207<210>12<211>454<212>PRT<213>智人(Homo sapiens)<400>12Met His Leu Thr Val Phe Leu Leu Lys Gly Ile Val Gly Phe Leu Trp1 5 10 15Ser Cys Trp Val Leu Val Gly Tyr Ala Lys Gly Gly Leu Gly Asp Asn20 25 30His Val His Ser Ser Phe Ile Tyr Arg Arg Leu Arg Asn His Glu Arg35 40 45Arg Glu Ile Gln Arg Glu Ile Leu Ser Ile Leu Gly Leu Pro His Arg50 55 60Pro Arg Pro Phe Ser Pro Gly Lys Gln Ala Ser Ser Ala Pro Leu Phe65 70 75 80Met Leu Asp Leu Tyr Asn Ala Met Thr Asn Glu Glu Asn Pro Glu Glu85 90 95Ser Glu Tyr Ser Val Arg Ala Ser Leu Ala Glu Glu Thr Arg Gly Ala100 105 110Arg Lys Gly Tyr Pro Ala Ser Pro Asn Gly Tyr Pro Arg Arg Ile Gln115 120 125Leu Ser Arg Thr Thr Pro Leu Thr Thr Gln Ser Pro Pro Leu Ala Ser130 135 140Leu His Asp Thr Asn Phe Leu Asn Asp Ala Asp Met Val Met Ser Phe145 150 155 160Val Asn Leu Val Glu Arg Asp Lys Asp Phe Ser His Gln Arg Arg His165 170 175Tyr Lys Glu Phe Arg Phe Asp Leu Thr Gln Ile Pro His Gly Glu Ala180 185 190Val Thr Ala Ala Glu Phe Arg Ile Tyr Lys Asp Arg Ser Asn Asn Arg195 200 205Phe Glu Asn Glu Thr Ile Lys Ile Ser Ile Tyr Gln Ile Ile Lys Glu210 215 220
Tyr Thr Asn Arg Asp Ala Asp Leu Phe Leu Leu Asp Thr Arg Lys Ala225 230 235 240Gln Ala Leu Asp Val Gly Trp Leu Val Phe Asp Ile Thr Val Thr Ser245 250 255Asn His Trp Val Ile Asn Pro Gln Asn Asn Leu Gly Leu Gln Leu Cys260 265 270Ala Glu Thr Gly Asp Gly Arg Ser Ile Asn Val Lys Ser Ala Gly Leu275 280 285Val Gly Arg Gln Gly Pro Gln Ser Lys Gln Pro Phe Met Val Ala Phe290 295 300Phe Lys Ala Ser Glu Val Leu Leu Arg Ser Val Arg Ala Ala Asn Lys305 310 315 320Arg Lys Asn Gln Asn Arg Asn Lys Ser Ser Ser His Gln Asp Ser Ser325 330 335Arg Met Ser Ser Val Gly Asp Tyr Asn Thr Ser Glu Gln Lys Gln Ala340 345 350Cys Lys Lys His Glu Leu Tyr Val Ser Phe Arg Asp Leu Gly Trp Gln355 360 365Asp Trp Ile Ile Ala Pro Glu Gly Tyr Ala Ala Phe Tyr Cys Asp Gly370 375 380Glu Cys Ser Phe Pro Leu Asn Ala His Met Asn Ala Thr Asn His Ala385 390 395 400Ile Val Gln Thr Leu Val His Leu Met Phe Pro Asp His Val Pro Lys405 410 415Pro Cys Cys Ala Pro Thr Lys Leu Asn Ala Ile Ser Val Leu Tyr Phe420 425 430Asp Asp Ser Ser Asn Val Ile Leu Lys Lys Tyr Arg Asn Met Val Val435 440 445Arg Ser Cys Gly Cys His450<210>13<211>396<212>DNA<213>智人(Homo sapiens)<400>13
aatcaaaacc gcaataaatc cagctctcat caggactcct ccagaatgtc cagtgttgga60gattataaca caagtgagca aaaacaagcc tgtaagaagc acgaactcta tgtgagcttc 120cgggatctgg gatggcagga ctggattata gcaccagaag gatacgctgc attttattgt 180gatggagaat gttcttttcc acttaacgcc catatgaatg ccaccaacca cgctatagtt 240cagactctgg ttcatctgat gtttcctgac cacgtaccaa agccttgttg tgctccaacc 300aaattaaatg ccatctctgt tctgtacttt gatgacagct ccaatgtcat tttgaaaaaa 360tatagaaata tggtagtacg ctcatgtggc tgccac 396<210>14<211>132<212>PRT<213>智人(Homo sapiens)<400>14Asn Gln Asn Arg Asn Lys Ser Ser Ser His Gln Asp Ser Ser Arg Met1 5 10 15Ser Set Val Gly Asp Tyr Asn Thr Ser Glu Gln Lys Gln Ala Cys Lys20 25 30Lys His Glu Leu Tyr Val Ser Phe Arg Asp Leu Gly Trp Gln Asp Trp35 40 45Ile Ile Ala Pro Glu Gly Tyr Ala Ala Phe Tyr Cys Asp Gly Glu Cys50 55 60Ser Phe Pro Leu Asn Ala His Met Asn Ala Thr Asn His Ala Ile Val65 70 75 80Gln Thr Leu Val His Leu Met Phe Pro Asp His Val Pro Lys Pro Cys85 90 95Cys Ala Pro Thr Lys Leu Asn Ala Ile Ser Val Leu Tyr Phe Asp Asp100 105 110Ser Ser Asn Val Ile Leu Lys Lys Tyr Arg Asn Met Val Val Arg Ser115 120 125Cys Gly Cys His130<210>15<211>2943<212>DNA<213>智人(Homo sapiens)<400>15gcaactgggg gcgccccgga cgaccatgag agataaggac tgagggccag gaaggggaag 60cgagcccgcc gagaggtggc ggggactgct cacgccaagg gccacagcgg ccgcgctccg120gcctcgctcc gccgctccac gcctcgcggg atccgcgggg gcagcccggc cgggcgggga180tgccggggct ggggcggagg gcgcagtggc tgtgctggtg gtgggggctg ctgtgcagct240gctgcgggcc cccgccgctg cggccgccct tgcccgctgc cgcggccgcc gccgccgggg300
ggcagctgct gggggacggc gggagccccg gccgcacgga gcagccgccg ccgtcgccgc360agtcctcctc gggcttcctg taccggcggc tcaagacgca ggagaagcgg gagatgcaga420aggagatctt gtcggtgctg gggctcccgc accggccccg gcccctgcac ggcctccaac480agccgcagcc cccggcgctc cggcagcagg aggagcagca gcagcagcag cagctgcctc540gcggagagcc ccctcccggg cgactgaagt ccgcgcccct cttcatgctg gatctgtaca600acgccctgtc cgccgacaac gacgaggacg gggcgtcgga gggggagagg cagcagtcct660ggccccacga agcagccagc tcgtcccagc gtcggcagcc gcccccgggc gccgcgcacc720cgctcaaccg caagagcctt ctggcccccg gatctggcag cggcggcgcg tccccactga780ccagcgcgca ggacagcgcc ttcctcaacg acgcggacat ggtcatgagc tttgtgaacc840tggtggagta cgacaaggag ttctcccctc gtcagcgaca ccacaaagag ttcaagttca900acttatccca gattcctgag ggtgaggtgg tgacggctgc agaattccgc atctacaagg960actgtgttat ggggagtttt aaaaaccaaa cttttcttat cagcatttat caagtcttac 1020aggagcatca gcacagagac tctgacctgt ttttgttgga cacccgtgta gtatgggcct 1080cagaagaagg ctggctggaa tttgacatca cggccactag caatctgtgg gttgtgactc 1140cacagcataa catggggctt cagctgagcg tggtgacaag ggatggagtc cacgtccacc 1200cccgagccgc aggcctggtg ggcagagacg gcccttacga taagcagccc ttcatggtgg 1260ctttcttcaa agtgagtgag gtccacgtgc gcaccaccag gtcagcctcc agccggcgcc 1320gacaacagag tcgtaatcgc tctacccagt cccaggacgt ggcgcgggtc tccagtgctt 1380cagattacaa cagcagtgaa ttgaaaacag cctgcaggaa gcatgagctg tatgtgagtt 1440tccaagacct gggatggcag gactggatca ttgcacccaa gggctatgct gccaattact 1500gtgatggaga atgctccttc ccactcaacg cacacatgaa tgcaaccaac cacgcgattg 1560tgcagacctt ggttcacctt atgaaccccg agtatgtccc caaaccgtgc tgtgcgccaa 1620ctaagctaaa tgccatctcg gttctttact ttgatgacaa ctccaatgtc attctgaaaa 1680aatacaggaa tatggttgta agagcttgtg gatgccacta actcgaaacc agatgctggg 1740gacacacatt ctgccttgga ttcctagatt acatctgcct taaaaaaaca cggaagcaca 1800gttggaggtg ggacgatgag actttgaaac tatctcatgc cagtgcctta ttacccagga 1860agattttaaa ggacctcatt aataatttgc tcacttggta aatgacgtga gtagttgttg 1920gtctgtagca agctgagttt ggatgtctgt agcataaggt ctggtaactg cagaaacata 1980accgtgaagc tcttcctacc ctcctccccc aaaaacccac caaaattagt tttagctgta 2040gatcaagcta tttggggtgt ttgttagtaa atagggaaaa taatctcaaa ggagttaaat 2100gtattcttgg ctaaaggatc agctggttca gtactgtcta tcaaaggtag attttacaga 2160gaacagaaat cggggaagtg gggggaacgc ctctgttcag ttcattccca gaagtccaca 2220ggacgcacag cccaggccac agccagggct ccacggggcg cccttgtctc agtcattgct 2280gttgtatgtt cgtgctggag ttttgttggt gtgaaaatac acttatttca gccaaaacat 2340accatttcta cacctcaatc ctccatttgc tgtactcttt gctagtacca aaagtagact 2400gattacactg aggtgaggct acaaggggtg tgtaaccgtg taacacgtga aggcagtgct 2460cacctcttct ttaccagaac ggttctttga ccagcacatt aacttctgga ctgccggctc 2520tagtaccttt tcagtaaagt ggttctctgc ctttttacta tacagcatac cacgccacag 2580ggttagaacc aacgaagaaa ataaaatgag ggtgcccagc ttataagaat ggtgttaggg 2640ggatgagcat gctgtttatg aacggaaatc atgatttccc tgtagaaagt gaggctcaga 2700ttaaatttta gaatattttc taaatgtctt tttcacaatc atgtgactgg gaaggcaatt 2760tcatactaaa ctgattaaat aatacattta taatctacaa ctgtttgcac ttacagcttt 2820ttttgtaaat ataaactata atttattgtc tattttatat ctgttttgct gtggcgttgg 2880ggggggggcc gggcttttgg gggggggggt ttgtttgggg ggtgtcgtgg tgtgggcggg 2940cgg 2943<210>16<211>513<212>PRT<213>智人(Homo sapiens)<400>16
Met Pro Gly Leu Gly Arg Arg Ala Gln Trp Leu Cys Trp Trp Trp Gly1 5 10 15Leu Leu Cys Ser Cys Cys Gly Pro Pro Pro Leu Arg Pro Pro Leu Pro20 25 30Ala Ala Ala Ala Ala Ala Ala Gly Gly Gln Leu Leu Gly Asp Gly Gly35 40 45Ser Pro Gly Arg Thr Glu Gln Pro Pro Pro Ser Pro Gln Ser Ser Ser50 55 60Gly Phe Leu Tyr Arg Arg Leu Lys Thr Gln Glu Lys Arg Glu Met Gln65 70 75 80Lys Glu Ile Leu Ser Val Leu Gly Leu Pro His Arg Pro Arg Pro Leu85 90 95His Gly Leu Gln Gln Pro Gln Pro Pro Ala Leu Arg Gln Gln Glu Glu100 105 110Gln Gln Gln Gln Gln Gln Leu Pro Arg Gly Glu Pro Pro Pro Gly Arg115 120 125Leu Lys Ser Ala Pro Leu Phe Met Leu Asp Leu Tyr Asn Ala Leu Ser130 135 140Ala Asp Asn Asp Glu Asp Gly Ala Ser Glu Gly Glu Arg Gln Gln Ser145 150 155 160Trp Pro His Glu Ala Ala Ser Ser Ser Gln Arg Arg Gln Pro Pro Pro165 170 175Gly Ala Ala His Pro Leu Asn Arg Lys Ser Leu Leu Ala Pro Gly Ser180 185 190Gly Ser Gly Gly Ala Ser Pro Leu Thr Ser Ala Gln Asp Ser Ala Phe195 200 205Leu Asn Asp Ala Asp Met Val Met Ser Phe Val Asn Leu Val Glu Tyr210 215 220Asp Lys Glu Phe Ser Pro Arg Gln Arg His His Lys Glu Phe Lys Phe225 230 235 240Asn Leu Ser Gln Ile Pro Glu Gly Glu Val Val Thr Ala Ala Glu Phe245 250 255Arg Ile Tyr Lys Asp Cys Val Met Gly Ser Phe Lys Asn Gln Thr Phe260 265 270Leu Ile Ser Ile Tyr Gln Val Leu Gln Glu His Gln His Arg Asp Ser
275 280 285Asp Leu Phe Leu Leu Asp Thr Arg Val Val Trp Ala Ser Glu Glu Gly290 295 300Trp Leu Glu Phe Asp Ile Thr Ala Thr Ser Asn Leu Trp Val Val Thr305 310 315 320Pro Gln His Asn Met Gly Leu Gln Leu Ser Val Val Thr Arg Asp Gly325 330 335Val His Val His Pro Arg Ala Ala Gly Leu Val Gly Arg Asp Gly Pro340 345 350Tyr Asp Lys Gln Pro Phe Met Val Ala Phe Phe Lys Val Ser Glu Val355 360 365His Val Arg Thr Thr Arg Ser Ala Ser Ser Arg Arg Arg Gln Gln Ser370 375 380Arg Asn Arg Ser Thr Gln Ser Gln Asp Val Ala Arg Val Ser Ser Ala385 390 395 400Ser Asp Tyr Asn Ser Ser Glu Leu Lys Thr Ala Cys Arg Lys His Glu405 410 415Leu Tyr Val Ser Phe Gln Asp Leu Gly Trp Gln Asp Trp Ile Ile Ala420 425 430Pro Lys Gly Tyr Ala Ala Asn Tyr Cys Asp Gly Glu Cys Ser Phe Pro435 440 445Leu Asn Ala His Met Asn Ala Thr Asn His Ala Ile Val Gln Thr Leu450 455 460Val His Leu Met Asn Pro Glu Tyr Val Pro Lys Pro Cys Cys Ala Pro465 470 475 480Thr Lys Leu Asn Ala Ile Ser Val Leu Tyr Phe Asp Asp Asn Ser Asn485 490 495Val Ile Leu Lys Lys Tyr Arg Asn Met Val Val Arg Ala Cys Gly Cys500 505 510His<210>17<211>420<212>DNA<213>智人(Homo sapiens)<400>17
aggtcagcct ccagccggcg ccgacaacag agtcgtaatc gctctaccca gtcccaggac60gtggcgcggg tctccagtgc ttcagattac aacagcagtg aattgaaaac agcctgcagg 120aagcatgagc tgtatgtgag tttccaagac ctgggatggc aggactggat cattgcaccc 180aagggctatg ctgccaatta ctgtgatgga gaatgctcct tcccactcaa cgcacacatg 240aatgcaacca accacgcgat tgtgcagacc ttggttcacc ttatgaaccc cgagtatgtc 300cccaaaccgt gctgtgcgcc aactaagcta aatgccatct cggttcttta ctttgatgac 360aactccaatg tcattctgaa aaaatacagg aatatggttg taagagcttg tggatgccac 420<210>18<211>140<212>PRT<213>智人(Homo sapiens)<400>18Arg Ser Ala Ser Ser Arg Arg Arg Gln Gln Ser Arg Asn Arg Ser Thr1 5 10 15Gln Ser Gln Asp Val Ala Arg Val Ser Ser Ala Ser Asp Tyr Asn Ser20 25 30Ser Glu Leu Lys Thr Ala Cys Arg Lys His Glu Leu Tyr Val Ser Phe35 40 45Gln Asp Leu Gly Trp Gln Asp Trp Ile Ile Ala Pro Lys Gly Tyr Ala50 55 60Ala Asn Tyr Cys Asp Gly Glu Cys Ser Phe Pro Leu Asn Ala His Met65 70 75 80Asn Ala Thr Asn His Ala Ile Val Gln Thr Leu Val His Leu Met Asn85 90 95Pro Glu Tyr Val Pro Lys Pro Cys Cys Ala Pro Thr Lys Leu Asn Ala100 105 110Ile Ser Val Leu Tyr Phe Asp Asp Asn Ser Asn Val Ile Leu Lys Lys115 120 125Tyr Arg Asn Met Val Val Arg Ala Cys Gly Cys His130 135 140<210>19<211>1878<212>DNA<213>智人(Homo sapiens)<400>19gggcgcagcg gggcccgtct gcagcaagtg accgacggcc gggacggccg cctgccccct60ctgccacctg gggcggtgcg ggcccggagc ccggagcccg ggtagcgcgt agagccggcg 120cgatgcacgt gcgctcactg cgagctgcgg cgccgcacag cttcgtggcg ctctgggcac 180ccctgttcct gctgcgctcc gccctggccg acttcagcct ggacaacgag gtgcactcga 240
gcttcatcca ccggcgcctc cgcagccagg agcggcggga gatgcagcgc gagatcctct 300ccattttggg cttgccccac cgcccgcgcc cgcacctcca gggcaagcac aactcggcac 360ccatgttcat gctggacctg tacaacgcca tggcggtgga ggagggcggc gggcccggcg 420gccagggctt ctcctacccc tacaaggccg tcttcagtac ccagggcccc cctctggcca 480gcctgcaaga tagccatttc ctcaccgacg ccgacatggt catgagcttc gtcaacctcg 540tggaacatga caaggaattc ttccacccac gctaccacca tcgagagttc cggtttgatc 600tttccaagat cccagaaggg gaagctgtca cggcagccga attccggatc tacaaggact 660acatccggga acgcttcgac aatgagacgt tccggatcag cgtttatcag gtgctccagg 720agcacttggg cagggaatcg gatctcttcc tgctcgacag ccgtaccctc tgggcctcgg 780aggagggctg gctggtgttt gacatcacag ccaccagcaa ccactgggtg gtcaatccgc 840ggcacaacct gggcctgcag ctctcggtgg agacgctgga tgggcagagc atcaacccca 900agttggcggg cctgattggg cggcacgggc cccagaacaa gcagcccttc atggtggctt 960tcttcaaggc cacggaggtc cacttccgca gcatccggtc cacggggagc aaacagcgca 1020gccagaaccg ctccaagacg cccaagaacc aggaagccct gcggatggcc aacgtggcag 1080agaacagcag cagcgaccag aggcaggcct gtaagaagca cgagctgtat gtcagcttcc 1140gagacctggg ctggcaggac tggatcatcg cgcctgaagg ctacgccgcc tactactgtg 1200agggggagtg tgccttccct ctgaactcct acatgaacgc caccaaccac gccatcgtgc 1260agacgctggt ccacttcatc aacccggaaa cggtgcccaa gccctgctgt gcgcccacgc 1320agctcaatgc catctccgtc ctctacttcg atgacagctc caacgtcatc ctgaagaaat 1380acagaaacat ggtggtccgg gcctgtggct gccactagct cctccgagaa ttcagaccct 1440ttggggccaa gtttttctgg atcctccatt gctcgccttg gccaggaacc agcagaccaa 1500ctgccttttg tgagaccttc ccctccctat ccccaacttt aaaggtgtga gagtattagg 1560aaacatgagc agcatatggc ttttgatcag tttttcagtg gcagcatcca atgaacaaga 1620tcctacaagc tgtgcaggca aaacctagca ggaaaaaaaa acaacgcata aagaaaaatg 1680gccgggccag gtcattggct gggaagtctc agccatgcac ggactcgttt ccagaggtaa 1740ttatgagcgc ctaccagcca ggccacccag ccgtgggagg aagggggcgt ggcaaggggt 1800gggcacattg gtgtctgtgc gaaaggaaaa ttgacccgga agttcctgta ataaatgtca 1860caataaaacg aatgaatg1878<210>20<211>431<212>PRT<213>智人(Homo sapiens)<400>20Met His Val Arg Ser Leu Arg Ala Ala Ala Pro His Ser Phe Val Ala1 5 10 15Leu Trp Ala Pro Leu Phe Leu Leu Arg Ser Ala Leu Ala Asp Phe Ser20 25 30Leu Asp Asn Glu Val His Ser Ser Phe Ile His Arg Arg Leu Arg Ser35 40 45Gln Glu Arg Arg Glu Met Gln Arg Glu Ile Leu Ser Ile Leu Gly Leu50 55 60Pro His Arg Pro Arg Pro His Leu Gln Gly Lys His Asn Ser Ala Pro65 70 75 80Met Phe Met Leu Asp Leu Tyr Asn Ala Met Ala Val Glu Glu Gly Gly85 90 95
Gly Pro Gly Gly Gln Gly Phe Ser Tyr Pro Tyr Lys Ala Val Phe Ser100 105 110Thr Gln Gly Pro Pro Leu Ala Ser Leu Gln Asp Ser His Phe Leu Thr115 120 125Asp Ala Asp Met Val Met Ser Phe Val Asn Leu Val Glu His Asp Lys130 135 140Glu Phe Phe His Pro Arg Tyr His His Arg Glu Phe Arg Phe Asp Leu145 150 155 160Ser Lys Ile Pro Glu Gly Glu Ala Val Thr Ala Ala Glu Phe Arg Ile165 170 175Tyr Lys Asp Tyr Ile Arg Glu Arg Phe Asp Asn Glu Thr Phe Arg Ile180 185 190Ser Val Tyr Gln Val Leu Gln Glu His Leu Gly Arg Glu Ser Asp Leu195 200 205Phe Leu Leu Asp Ser Arg Thr Leu Trp Ala Ser Glu Glu Gly Trp Leu210 215 220Val Phe Asp Ile Thr Ala Thr Ser Asn His Trp Val Val Asn Pro Arg225 230 235 240His Asn Leu Gly Leu Gln Leu Ser Val Glu Thr Leu Asp Gly Gln Ser245 250 255Ile Asn Pro Lys Leu Ala Gly Leu Ile Gly Arg His Gly Pro Gln Asn260 265 270Lys Gln Pro Phe Met Val Ala Phe Phe Lys Ala Thr Glu Val His Phe275 280 285Arg Ser Ile Arg Ser Thr Gly Ser Lys Gln Arg Ser Gln Asn Arg Ser290 295 300Lys Thr Pro Lys Asn Gln Glu Ala Leu Arg Met Ala Asn Val Ala Glu305 310 315 320Asn Ser Ser Ser Asp Gln Arg Gln Ala Cys Lys Lys His Glu Leu Tyr325 330 335Val Ser Phe Arg Asp Leu Gly Trp Gln Asp Trp Ile Ile Ala Pro Glu340 345 350Gly Tyr Ala Ala Tyr Tyr Cys Glu Gly Glu Cys Ala Phe Pro Leu Asn355 360 365
Ser Tyr Met Asn Ala Thr Asn His Ala Ile Val Gln Thr Leu Val His370 375 380Phe Ile Asn Pro Glu Thr Val Pro Lys Pro Cys Cys Ala Pro Thr Gln385 390 395 400Leu Asn Ala Ile Ser Val Leu Tyr Phe Asp Asp Ser Ser Asn Val Ile405 410 415Leu Lys Lys Tyr Arg Asn Met Val Val Arg Ala Cys Gly Cys His420 425 430<210>21<211>417<212>DNA<213>智人(Homo sapiens)<400>21tccacgggga gcaaacagcg cagccagaac cgctccaaga cgcccaagaa ccaggaagcc 60ctgcggatgg ccaacgtggc agagaacagc agcagcgacc agaggcaggc ctgtaagaag120cacgagctgt atgtcagctt ccgagacctg ggctggcagg actggatcat cgcgcctgaa180ggctacgccg cctactactg tgagggggag tgtgccttcc ctctgaactc ctacatgaac240gccaccaacc acgccatcgt gcagacgctg gtccacttca tcaacccgga aacggtgccc300aagccctgct gtgcgcccac gcagctcaat gccatctccg tcctctactt cgatgacagc360tccaacgtca tcctgaagaa atacagaaac atggtggtcc gggcctgtgg ctgccac 417<210>22<21l>139<212>PRT<213>智人(Homo sapiens)<400>22Ser Thr Gly Ser Lys Gln Arg Ser Gln Asn Arg Ser Lys Thr Pro Lys1 5 10 15Asn Gln Glu Ala Leu Arg Met Ala Asn Val Ala Glu Asn Ser Ser Ser20 25 30Asp Gln Arg Gln Ala Cys Lys Lys His Glu Leu Tyr Val Ser Phe Arg35 40 45Asp Leu Gly Trp Gln Asp Trp Ile Ile Ala Pro Glu Gly Tyr Ala Ala50 55 60Tyr Tyr Cys Glu Gly Glu Cys Ala Phe Pro Leu Asn Ser Tyr Met Asn65 70 75 80Ala Thr Asn His Ala Ile Val Gln Thr Leu Val His Phe Ile Asn Pro85 90 95Glu Thr Val Pro Lys Pro Cys Cys Ala Pro Thr Gln Leu Asn Ala Ile100 105 110
Ser Val Leu Tyr Phe Asp Asp Ser Ser Asn Val Ile Leu Lys Lys Tyr115 120 125Arg Asn Met Val Val Arg Ala Cys Gly Cys His130 135<210>23<211>3536<212>DNA<213>智人(Homo sapiens)<400>23ccgcccgtcc cgccccgccc cgccgcccgc cgcccgccga gcccagcctc cttgccgtcg60gggcgtcccc aggccctggg tcggccgcgg agccgatgcg cgcccgctga gcgccccagc 120tgagcgcccc cggcctgcca tgaccgcgct ccccggcccg ctctggctcc tgggcctggc 180gctatgcgcg ctgggcgggg gcggccccgg cctgcgaccc ccgcccggct gtccccagcg 240acgtctgggc gcgcgcgagc gccgggacgt gcagcgcgag atcctggcgg tgctcgggct 300gcctgggcgg ccccggcccc gcgcgccacc cgccgcctcc cggctgcccg cgtccgcgcc 360gctcttcatg ctggacctgt accacgccat ggccggcgac gacgacgagg acggcgcgcc 420cgcggagcgg cgcctgggcc gcgccgacct ggtcatgagc ttcgttaaca tggtggagcg 480agaccgtgcc ctgggccacc aggagcccca ttggaaggag ttccgctttg acctgaccca 540gatcccggct ggggaggcgg tcacagctgc ggagttccgg atttacaagg tgcccagcat 600ccacctgctc aacaggaccc tccacgtcag catgttccag gtggtccagg agcagtccaa 660cagggagtct gacttgttct ttttggatct tcagacgctc cgagctggag acgagggctg 720gctggtgctg gatgtcacag cagccagtga ctgctggttg ctgaagcgtc acaaggacct 780gggactccgc ctctatgtgg agactgagga cgggcacagc gtggatcctg gcctggccgg 840cctgctgggt caacgggccc cacgctccca acagcctttc gtggtcactt tcttcagggc 900cagtccgagt cccatccgca cccctcgggc agtgaggcca ctgaggagga ggcagccgaa 960gaaaagcaac gagctgccgc aggccaaccg actcccaggg atctttgatg acgtccacgg 1020ctcccacggc cggcaggtct gccgtcggca cgagctctac gtcagcttcc aggacctcgg 1080ctggctggac tgggtcatcg ctccccaagg ctactcggcc tattactgtg agggggagtg 1140ctccttccca ctggactcct gcatgaatgc caccaaccac gccatcctgc agtccctggt 1200gcacctgatg atgccagacg cagtccccaa ggcgtgctgt gcacccacca agctgagcgc 1260cacctctgtg ctctactatg acagcagcaa caatgtcatc ctgcgcaagc accgcaacat 1320ggtggtcaag gcctgcggct gccactgagt ccacccgccc ggcccagctg cagccaccct 1380tctcatctgg atcgggcccc tcagaagcag gaaaccctca aacccagcca gaccccaggc 1440cggggcattg ccagggagga ccctcacaac cacgtacatg accctttctc cttcatgcca 1500ggctcctatg ctccccttgc cctgccaggc atttgtgtga ctgtcctgtt tccagcccag 1560gtggtctcaa tcatcaggca gtgttctacc caaatgcaaa cgcctctccc ggaggcatgt 1620cctggctggt tctttggggt tggcacagaa gtcctgtctg aggtcctatc catgcccctt 1680actggctcag gtcgtgagat agatgtggaa tgacctgaga ggcacctgga gcccactgtt 1740ggccaccttg agctcttcac catccatcac agggtgtggt gtgtgtagtc agggtctggt 1800tggctcccca ttgcctgccc gaggtgcaag gtggggtata aaactggata acccctgaag 1860tattgtatat tcatggatct gaagcactga tccactggtc acaggtagac atgtggagtc 1920aactcaagaa aaagctgagt gaacagcatg atttagggct aaagccaatg gcatttatct 1980tcccttgtct tcctgctttg catttgcctc tgccatctag gaaagacatg taagagcatg 2040gacattttac tttggagaaa cagaaaaatc ttggggcttc caattgaccc atctatctgc 2100caccatgttg ccccaccagg agctcagctc tgtggagttt tccctttgct gagcaagcat 2160gtggttgcat tgggtggccc aggatgacaa tgcacagcac agatgccatc atttcccttt 2220cccctctgaa tggcagacat cagtaatcaa tctggaatgt ttttcttcca aatctgagtg 2280gaattttcaa atgatcagca cagccactgc caacagatat gatgtaaagt gaaacctggt 2340
tgccatcttc tgccatgctg aggagcagtc catccctgcc cgagcatgta tcggcaacat 2400gggcagcctg tgaccgggtc tggggcgagg ccaggggcca tcaaaaacag gctgatcacc 2460aaagtcagtg tcaccctgga tgcccagcag ccctgtcctg tgtcttgggc ctgtgagtca 2520aagaaaaggt ccttttcagg gagtgacaag tagtaattag gctgagttgg gtggagaggt 2580ttgtctcagc ctctgctgtt ctcggaaact gctgttctcc ttggagcagc cactgggagt 2640tggagtgttt atttgatttc tgacttgcta agcctgtaat ttacctgctg gaatagacag 2700agtccagctg cccaaaccgt gtcattaaaa gcagatcctg cgcccgcccc atccacaggc 2760acagcccggc agagtggttc cacctcccca tgggcccaag gatgcgcctc tctggagttc 2820acgtgctgca cccccaggga ggggcctggg gaaagctggt ccagcagcag gggtggaggc 2880tggggccaca ctgcgggaca gcagcccctc cacctggacc agggagggcc tccatgtgca 2940agcgcagagg aagagaccct cccatgtacg caaagggcag ccccaggctg tctggaagtt 3000ggagaattcc ctatcagcac agggatctca gctctggcct ggaggtgaag agacctgcct 3060tgtaggtggc ttccttatct gcgcctccat tttctatctg cactttttga tctccaaaca 3120accttcagcc aaagaatctg tctaccaact cctcatagtg agccagaagc agcctcataa 3180ccctgaatgt ggggctctgg tggctgtcac gaagcagagt tggcacataa catggaacct 3240ggccaggcat ggtggctcac acctataacc ccagcacttt gggaggccaa ggcaggcaga 3300tcacctgaag tcaggagttc aagaccatcc tggccaacac agtgaaaccc catctgtact 3360aaaaatacaa gattacctgg gcatggtggt gcatgcctat aatcccagct actcaggagg 3420ctgaggcaga attgcttgaa cctgggaggt ggaggttgca gtgagcagag atcacaacat 3480tgcacttcag cctggtgaca tgagcaaaac tgttgtctca acaaaatgaa attatg 3536<210>24<211>402<212>PRT<213>智人(Homo sapiens)<400>24Met Thr Ala Leu Pro Gly Pro Leu Trp Leu Leu Gly Leu Ala Leu Cys1 5 10 15Ala Leu Gly Gly Gly Gly Pro Gly Leu Arg Pro Pro Pro Gly Cys Pro20 25 30Gln Arg Arg Leu Gly Ala Arg Glu Arg Arg Asp Val Gln Arg Glu Ile35 40 45Leu Ala Val Leu Gly Leu Pro Gly Arg Pro Arg Pro Arg Ala Pro Pro50 55 60Ala Ala Ser Arg Leu Pro Ala Ser Ala Pro Leu Phe Met Leu Asp Leu65 70 75 80Tyr His Ala Met Ala Gly Asp Asp Asp Glu Asp Gly Ala Pro Ala Glu85 90 95Arg Arg Leu Gly Arg Ala Asp Leu Val Met Ser Phe Val Asn Met Val100 105 110Glu Arg Asp Arg Ala Leu Gly His Gln Glu Pro His Trp Lys Glu Phe115 120 125Arg Phe Asp Leu Thr Gln Ile Pro Ala Gly Glu Ala Val Thr Ala Ala
130 135 140Glu Phe Arg Ile Tyr Lys Val Pro Ser Ile His Leu Leu Asn Arg Thr145 150 155 160Leu His Val Ser Met Phe Gln Val Val Gln Glu Gln Ser Asn Arg Glu165 170 175Ser Asp Leu Phe Phe Leu Asp Leu Gln Thr Leu Arg Ala Gly Asp Glu180 185 190Gly Trp Leu Val Leu Asp Val Thr Ala Ala Ser Asp Cys Trp Leu Leu195 200 205Lys Arg His Lys Asp Leu Gly Leu Arg Leu Tyr Val Glu Thr Glu Asp210 215 220Gly His Ser Val Asp Pro Gly Leu Ala Gly Leu Leu Gly Gln Arg Ala225 230 235 240Pro Arg Ser Gln Gln Pro Phe Val Val Thr Phe Phe Arg Ala Ser Pro245 250 255Ser Pro Ile Arg Thr Pro Arg Ala Val Arg Pro Leu Arg Arg Arg Gln260 265 270Pro Lys Lys Ser Asn Glu Leu Pro Gln Ala Asn Arg Leu Pro Gly Ile275 280 285Phe Asp Asp Val His Gly Ser His Gly Arg Gln Val Cys Arg Arg His290 295 300Glu Leu Tyr Val Ser Phe Gln Asp Leu Gly Trp Leu Asp Trp Val Ile305 310 315 320Ala Pro Gln Gly Tyr Ser Ala Tyr Tyr Cys Glu Gly Glu Cys Ser Phe325 330 335Pro Leu Asp Ser Cys Met Asn Ala Thr Asn His Ala Ile Leu Gln Ser340 345 350Leu Val His Leu Met Met Pro Asp Ala Val Pro Lys Ala Cys Cys Ala355 360 365Pro Thr Lys Leu Ser Ala Thr Ser Val Leu Tyr Tyr Asp Ser Ser Asn370 375 380Asn Val Ile Leu Arg Lys His Arg Asn Met Val Val Lys Ala Cys Gly385 390 395 400Cys His
<210>25<211>417<212>DNA<213>智人(Homo sapiens)<400>25gcagtgaggc cactgaggag gaggcagccg aagaaaagca acgagctgcc gcaggccaac 60cgactcccag ggatctttga tgacgtccac ggctcccacg gccggcaggt ctgccgtcgg 120cacgagctct acgtcagctt ccaggacctc ggctggctgg actgggtcat cgctccccaa 180ggctactcgg cctattactg tgagggggag tgctccttcc cactggactc ctgcatgaat 240gccaccaacc acgccatcct gcagtccctg gtgcacctga tgatgccaga cgcagtcccc 300aaggcgtgct gtgcacccac caagctgagc gccacctctg tgctctacta tgacagcagc 360aacaatgtca tcctgcgcaa gcaccgcaac atggtggtca aggcctgcgg ctgccac 417<210>26<211>139<212>PRT<213>智人(Homo sapiens)<400>26Ala Val Arg Pro Leu Arg Arg Arg Gln Pro Lys Lys Ser Asn Glu Leu1 5 10 15Pro Gln Ala Asn Arg Leu Pro Gly Ile Phe Asp Asp Val His Gly Ser20 25 30His Gly Arg Gln Val Cys Arg Arg His Glu Leu Tyr Val Ser Phe Gln35 40 45Asp Leu Gly Trp Leu Asp Trp Val Ile Ala Pro Gln Gly Tyr Ser Ala50 55 60Tyr Tyr Cys Glu Gly Glu Cys Ser Phe Pro Leu Asp Ser Cys Met Asn65 70 75 80Ala Thr Asn His Ala Ile Leu Gln Ser Leu Val His Leu Met Met Pro85 90 95Asp Ala Val Pro Lys Ala Cys Cys Ala Pro Thr Lys Leu Ser Ala Thr100 105 110Ser Val Leu Tyr Tyr Asp Ser Ser Asn Asn Val Ile Leu Arg Lys His115 120 125Arg Asn Met Val Val Lys Ala Cys Gly Cys His130 135<210>27<211>1942<212>DNA<213>智人(Homo sapiens)
<400>27cggtccagcc cggcagcggg tgagagtggg tgctggccag gacggttcct tcagagcaaa 60cagcagggag atgccggccc gctccttccc agctcctccc cgtgcccgct aacacagcac120ggccgcctgc agtctcctct ctgggtgatt gcgcgggcct aagatgtgtc ctggggcact180gtgggtggcc ctgcccctgc tgtccctgct ggctggctcc ctacagggga agccactgca240gagctgggga cgagggtctg ctgggggaaa cgcccacagc ccactggggg tgcctggagg300tgggctgcct gagcacacct tcaacctgaa gatgtttctg gagaacgtga aggtggattt360cctgcgcagc cttaacctga gtggggtccc ttcgcaggac aaaaccaggg tggagccgcc420gcagtacatg attgacctgt acaacaggta cacgtccgat aagtcgacta cgccagcgtc480caacattgtg cggagcttca gcatggaaga tgccatctcc ataactgcca cagaggactt540ccccttccag aagcacatct tgctcttcaa catctccatt cctaggcatg agcagatcac600cagagctgag ctccgactct atgtctcctg tcaaaatcac gtggacccct ctcatgacct660gaaaggaagc gtggtcattt atgatgttct ggatggaaca gatgcctggg atagtgctac720agagaccaag accttcctgg tgtcccagga cattcaggat gagggctggg agaccttgga780agtgtccagc gccgtgaagc gctgggtccg gtccgactcc accaagagca aaaataagct840ggaagtgact gtggagagcc acaggaaggg ctgcgacacg ctggacatca gtgtcccccc900aggttccaga aacctgccct tctttgttgt cttctccaat gaccacagca gtgggaccaa960ggagaccagg ctggagctga gggagatgat cagccatgaa caagagagcg tgctcaagaa 1020gctgtccaag gacggctcca cagaggcagg tgagagcagt cacgaggagg acacggatgg 1080ccacgtggct gcggggtcga ctttagccag gcggaaaagg agcgccgggg ctggcagcca 1140ctgtcaaaag acctccctgc gggtaaactt cgaggacatc ggctgggaca gctggatcat 1200tgcacccaag gagtatgaag cctacgagtg taagggcggc tgcttcttcc ccttggctga 1260cgatgtgacg ccgacgaaac acgctatcgt gcagaccctg gtgcatctca agttccccac 1320aaaggtgggc aaggcctgct gtgtgcccac caaactgagc cccatctccg tcctctacaa 1380ggatgacatg ggggtgccca ccctcaagta ccattacgag ggcatgagcg tggcagagtg 1440tgggtgcagg tagtatctgc ctgcggggct ggggaggcag gccaaagggg ctccacatga 1500gaggtcctgc atgcccctgg gcacaacaag gactgattca atctgcatgc cagcctggag 1560gaggaaaggg agcctgctct ccctccccac accccaccca aagcatacac cgctgagctc 1620aactgccagg gaaggctaag gaaatgggga tttgagcaca acaggaaagc ctgggagggt 1680tgttgggatg caaggaggtg atgaaaagga gacaggggga aaaataatcc atagtcagca 1740gaaaacaaca gcagtgagcc agaggagcac aggcgggcag gtcactgcag agactgatgg 1800aagttagaga ggtggaggag gccagctcgc tccaaaaccc ttggggagta gagggaagga 1860gcaggccgcg tgtcacaccc atcattgtat gttatttccc acaacccagt tggaggggca 1920tggcttccaa tttagagacc cg1942<210>28<211>429<212>PRT<213>智人(Homo sapiens)<400>28Met Cys Pro Gly Ala Leu Trp Val Ala Leu Pro Leu Leu Ser Leu Leu1 5 10 15Ala Gly Ser Leu Gln Gly Lys Pro Leu Gln Ser Trp Gly Arg Gly Ser20 25 30Ala Gly Gly Asn Ala His Ser Pro Leu Gly Val Pro Gly Gly Gly Leu35 40 45Pro Glu His Thr Phe Asn Leu Lys Met Phe Leu Glu Asn Val Lys Val
50 55 60Asp Phe Leu Arg Ser Leu Asn Leu Ser Gly Val Pro Ser Gln Asp Lys65 70 75 80Thr Arg Val Glu Pro Pro Gln Tyr Met Ile Asp Leu Tyr Asn Arg Tyr85 90 95Thr Ser Asp Lys Ser Thr Thr Pro Ala Ser Asn Ile Val Arg Ser Phe100 105 110Ser Met Glu Asp Ala Ile Ser Ile Thr Ala Thr Glu Asp Phe Pro Phe115 120 125Gln Lys His Ile Leu Leu Phe Asn Ile Ser Ile Pro Arg His Glu Gln130 135 140Ile Thr Arg Ala Glu Leu Arg Leu Tyr Val Ser Cys Gln Asn His Val145 150 155 160Asp Pro Ser His Asp Leu Lys Gly Ser Val Val Ile Tyr Asp Val Leu165 170 175Asp Gly Thr Asp Ala Trp Asp Ser Ala Thr Glu Thr Lys Thr Phe Leu180 185 190Val Ser Gln Asp Ile Gln Asp Glu Gly Trp Glu Thr Leu Glu Val Ser195 200 205Ser Ala Val Lys Arg Trp Val Arg Ser Asp Ser Thr Lys Ser Lys Asn210 215 220Lys Leu Glu Val Thr Val Glu Ser His Arg Lys Gly Cys Asp Thr Leu225 230 235 240Asp Ile Ser Val Pro Pro Gly Ser Arg Asn Leu Pro Phe Phe Val Val245 250 255Phe Ser Asn Asp His Ser Ser Gly Thr Lys Glu Thr Arg Leu Glu Leu260 265 270Arg Glu Met Ile Ser His Glu Gln Glu Ser Val Leu Lys Lys Leu Ser275 280 285Lys Asp Gly Ser Thr Glu Ala Gly Glu Ser Ser His Glu Glu Asp Thr290 295 300Asp Gly His Val Ala Ala Gly Ser Thr Leu Ala Arg Arg Lys Arg Ser305 310 315 320Ala Gly Ala Gly Ser His Cys Gln Lys Thr Ser Leu Arg Val Asn Phe325 330 335
Glu Asp Ile Gly Trp Asp Ser Trp Ile Ile Ala Pro Lys Glu Tyr Glu340 345 350Ala Tyr Glu Cys Lys Gly Gly Cys Phe Phe Pro Leu Ala Asp Asp Val355 360 365Thr Pro Thr Lys His Ala Ile Val Gln Thr Leu Val His Leu Lys Phe370 375 380Pro Thr Lys Val Gly Lys Ala Cys Cys Val Pro Thr Lys Leu Ser Pro385 390 395 400Ile Ser Val Leu Tyr Lys Asp Asp Met Gly Val Pro Thr Leu Lys Tyr405 410 415His Tyr Glu Gly Met Ser Val Ala Glu Cys Gly Cys Arg420 425<210>29<211>1584<212>DNA<213>智人(Homo sapiens)<400>29ggggagagga agagtggtag ggggagggag agagagagga agagtttcca aacttgtctc 60cagtgacagg agacatttac gttccacaag ataaaactgc cacttagagc ccagggaagc120taaaccttcc tggcttggcc taggagctcg agcggagtca tgggctctct ggtcctgaca180ctgtgcgctc ttttctgcct ggcagcttac ttggtttctg gcagccccat catgaaccta240gagcagtctc ctctggaaga agatatgtcc ctctttggtg atgttttctc agagcaagac300ggtgtcgact ttaacacact gctccagagc atgaaggatg agtttcttaa gacactaaac360ctctctgaca tccccacgca ggattcagcc aaggtggacc caccagagta catgttggaa420ctctacaaca aatttgcaac agatcggacc tccatgccct ctgccaacat cattaggagt480ttcaagaatg aagatctgtt ttcccagccg gtcagtttta atgggctccg aaaatacccc540ctcctcttca atgtgtccat tcctcaccat gaagaggtca tcatggctga acttaggcta600tacacactgg tgcaaaggga tcgtatgata tacgatggag tagaccggaa aattaccatt660tttgaagtgc tggagagcaa aggggataat gagggagaaa gaaacatgct ggtcttggtg720tctggggaga tatatggaac caacagtgag tgggagactt ttgatgtcac agatgccatc780agacgttggc aaaagtcagg ctcatccacc caccagctgg aggtccacat tgagagcaaa840cacgatgaag ctgaggatgc cagcagtgga cggctagaaa tagataccag tgcccagaat900aagcataacc ctttgctcat cgtgttttct gatgaccaaa gcagtgacaa ggagaggaag960gaggaactga atgaaatgat ttcccatgag caacttccag agctggacaa cttgggcctg 1020gatagctttt ccagtggacc tggggaagag gctttgttgc agatgagatc aaacatcatc 1080tatgactcca ctgcccgaat cagaaggaac gccaaaggaa actactgtaa gaggaccccg 1140ctctacatcg acttcaagga gattgggtgg gactcctgga tcatcgctcc gcctggatac 1200gaagcctatg aatgccgtgg tgtttgtaac taccccctgg cagagcatct cacacccaca 1260aagcatgcaa ttatccaggc cttggtccac ctcaagaatt cccagaaagc ttccaaagcc 1320tgctgtgtgc ccacaaagct agagcccatc tccatcctct atttagacaa aggcgtcgtc 1380acctacaagt ttaaatacga aggcatggcc gtctccgaat gtggctgtag atagaagaag 1440agtcctatgg cttatttaat aactgtaaat gtgtatattt ggtgttccta tttaatgaga 1500ttatttaata agggtgtaca gtaatagagg cttgctgcct tcaggaaatg gacaggtcag 1560tttgttgtag gaaatgcata tttt 1584
<210>30<211>424<212>PRT<213>智人(Homo sapiens)<400>30Met Gly Ser Leu Val Leu Thr Leu Cys Ala Leu Phe Cys Leu Ala Ala1 5 10 15Tyr Leu Val Ser Gly Ser Pro Ile Met Asn Leu Glu Gln Ser Pro Leu20 25 30Glu Glu Asp Met Ser Leu Phe Gly Asp Val Phe Ser Glu Gln Asp Gly35 40 45Val Asp Phe Asn Thr Leu Leu Gln Ser Met Lys Asp Glu Phe Leu Lys50 55 60Thr Leu Asn Leu Ser Asp Ile Pro Thr Gln Asp Ser Ala Lys Val Asp65 70 75 80Pro Pro Glu Tyr Met Leu Glu Leu Tyr Asn Lys Phe Ala Thr Asp Arg85 90 95Thr Ser Met Pro Ser Ala Asn Ile Ile Arg Ser Phe Lys Asn Glu Asp100 105 110Leu Phe Ser Gln Pro Val Ser Phe Asn Gly Leu Arg Lys Tyr Pro Leu115 120 125Leu Phe Asn Val Ser Ile Pro His His Glu Glu Val Ile Met Ala Glu130 135 140Leu Arg Leu Tyr Thr Leu Val Gln Arg Asp Arg Met Ile Tyr Asp Gly145 150 155 160Val Asp Arg Lys Ile Thr Ile Phe Glu Val Leu Glu Ser Lys Gly Asp165 170 175Asn Glu Gly Glu Arg Asn Met Leu Val Leu Val Ser Gly Glu Ile Tyr180 185 190Gly Thr Asn Ser Glu Trp Glu Thr Phe Asp Val Thr Asp Ala Ile Arg195 200 205Arg Trp Gln Lys Ser Gly Ser Ser Thr His Gln Leu Glu Val His Ile210 215 220Glu Ser Lys His Asp Glu Ala Glu Asp Ala Ser Ser Gly Arg Leu Glu225 230 235 240
Ile Asp Thr Ser Ala Gln Asn Lys His Asn Pro Leu Leu Ile Val Phe245 250 255Ser Asp Asp Gln Ser Ser Asp Lys Glu Arg Lys Glu Glu Leu Asn Glu260 265 270Met Ile Ser His Glu Gln Leu Pro Glu Leu Asp Asn Leu Gly Leu Asp275 280 285Ser Phe Ser Ser Gly Pro Gly Glu Glu Ala Leu Leu Gln Met Arg Ser290 295 300Asn Ile Ile Tyr Asp Ser Thr Ala Arg Ile Arg Arg Asn Ala Lys Gly305 310 315 320Asn Tyr Cys Lys Arg Thr Pro Leu Tyr Ile Asp Phe Lys Glu Ile Gly325 330 335Trp Asp Ser Trp Ile Ile Ala Pro Pro Gly Tyr Glu Ala Tyr Glu Cys340 345 350Arg Gly Val Cys Asn Tyr Pro Leu Ala Glu His Leu Thr Pro Thr Lys355 360 365His Ala Ile Ile Gln Ala Leu Val His Leu Lys Asn Ser Gln Lys Ala370 375 380Ser Lys Ala Cys Cys Val Pro Thr Lys Leu Glu Pro Ile Ser Ile Leu385 390 395 400Tyr Leu Asp Lys Gly Val Val Thr Tyr Lys Phe Lys Tyr Glu Gly Met405 410 415Ala Val Ser Glu Cys Gly Cys Arg420<210>31<211>324<212>DNA<213>智人(Homo sapiens)<400>31aacgccaaag gaaactactg taagaggacc ccgctctaca tcgacttcaa ggagattggg 60tgggactcct ggatcatcgc tccgcctgga tacgaagcct atgaatgccg tggtgtttgt120aactaccccc tggcagagca tctcacaccc acaaagcatg caattatcca ggccttggtc180cacctcaaga attcccagaa agcttccaaa gcctgctgtg tgcccacaaa gctagagccc240atctccatcc tctatttaga caaaggcgtc gtcacctaca agtttaaata cgaaggcatg300gccgtctccg aatgtggctg taga 324<210>32<211>108<212>PRT
<213>智人(Homo sapiens)<400>32Asn Ala Lys Gly Asn Tyr Cys Lys Arg Thr Pro Leu Tyr Ile Asp Phe1 5 10 15Lys Glu Ile Gly Trp Asp Ser Trp Ile Ile Ala Pro Pro Gly Tyr Glu20 25 30Ala Tyr Glu Cys Arg Gly Val Cys Asn Tyr Pro Leu Ala Glu His Leu35 40 45Thr Pro Thr Lys His Ala Ile Ile Gln Ala Leu Val His Leu Lys Asn50 55 60Ser Gln Lys Ala Ser Lys Ala Cys Cys Val Pro Thr Lys Leu Glu Pro65 70 75 80Ile Ser Ile Leu Tyr Leu Asp Lys Gly Val Val Thr Tyr Lys Phe Lys85 90 95Tyr Glu Gly Met Ala Val Ser Glu Cys Gly Cys Arg100 105<210>33<211>1443<212>DNA<213>智人(Homo sapiens)<400>33tctccgcccc ccagtacctc cctcccctcc cctccagcat ggtgctcgcg gccccgctgc 60tgctgggctt cctgctcctc gccctggagc tgcggccccg gggggaggcg gccgagggcc120ccgcggcggc ggcggcggcg gcggcggcgg cggcagcggc gggggtcggg ggggagcgct180ccagccggcc agccccgtcc gtggcgcccg agccggacgg ctgccccgtg tgcgtttggc240ggcagcacag ccgcgagctg cgcctagaga gcatcaagtc gcagatcttg agcaaactgc300ggctcaagga ggcgcccaac atcagccgcg aggtggtgaa gcagctgctg cccaaggcgc360cgccgctgca gcagatcctg gacctacacg acttccaggg cgacgcgctg cagcccgagg420acttcctgga ggaggacgag taccacgcca ccaccgagac cgtcattagc atggcccagg480agacggaccc agcagtacag acagatggca gccctctctg ctgccatttt cacttcagcc540ccaaggtgat gttcacaaag gtactgaagg cccagctgtg ggtgtaccta cggcctgtac600cccgcccagc cacagtctac ctgcagatct tgcgactaaa acccctaact ggggaaggga660ccgcaggggg agggggcgga ggccggcgtc acatccgtat ccgctcactg aagattgagc720tgcactcacg ctcaggccat tggcagagca tcgacttcaa gcaagtgcta cacagctggt780tccgccagcc acagagcaac tggggcatcg agatcaacgc ctttgatccc agtggcacag840acctggctgt cacctccctg gggccgggag ccgaggggct gcatccattc atggagcttc900gagtcctaga gaacacaaaa cgttcccggc ggaacctggg tctggactgc gacgagcact960caagcgagtc ccgctgctgc cgatatcccc tcacagtgga ctttgaggct ttcggctggg 1020actggatcat cgcacctaag cgctacaagg ccaactactg ctccggccag tgcgagtaca 1080tgttcatgca aaaatatccg catacccatt tggtgcagca ggccaatcca agaggctctg 1140ctgggccctg ttgtaccccc accaagatgt ccccaatcaa catgctctac ttcaatgaca 1200agcagcagat tatctacggc aagatccctg gcatggtggt ggatcgctgt ggctgctctt 1260aaggtggggg atagaggatg cctcccccac agaccctacc ccaagacccc tagccctgcc 1320
cccatccccc caagccctag agctccctcc actcttcccg cgaacatcac accgttcccc 1380gaccaagccg tgtgcaatac aacagaggga ggcaggtggg aattgagggt gaggggtttg 1440ggg1443<210>34<211>407<212>PRT<213>智人(Homo sapiens)<400>34Met Val Leu Ala Ala Pro Leu Leu Leu Gly Phe Leu Leu Leu Ala Leu1 5 10 15Glu Leu Arg Pro Arg Gly Glu Ala Ala Glu Gly Pro Ala Ala Ala Ala20 25 30Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Val Gly Gly Glu Arg Ser35 40 45Ser Arg Pro Ala Pro Ser Val Ala Pro Glu Pro Asp Gly Cys Pro Val50 55 60Cys Val Trp Arg Gln His Ser Arg Glu Leu Arg Leu Glu Ser Ile Lys65 70 75 80Ser Gln Ile Leu Ser Lys Leu Arg Leu Lys Glu Ala Pro Asn Ile Ser85 90 95Arg Glu Val Val Lys Gln Leu Leu Pro Lys Ala Pro Pro Leu Gln Gln100 105 110Ile Leu Asp Leu His Asp Phe Gln Gly Asp Ala Leu Gln Pro Glu Asp115 120 125Phe Leu Glu Glu Asp Glu Tyr His Ala Thr Thr Glu Thr Val Ile Ser130 135 140Met Ala Gln Glu Thr Asp Pro Ala Val Gln Thr Asp Gly Ser Pro Leu145 150 155 160Cys Cys His Phe His Phe Ser Pro Lys Val Met Phe Thr Lys Val Leu165 170 175Lys Ala Gln Leu Trp Val Tyr Leu Arg Pro Val Pro Arg Pro Ala Thr180 185 190Val Tyr Leu Gln Ile Leu Arg Leu Lys Pro Leu Thr Gly Glu Gly Thr195 200 205Ala Gly Gly Gly Gly Gly Gly Arg Arg His Ile Arg Ile Arg Ser Leu210 215 220
Lys Ile Glu Leu His Ser Arg Ser Gly His Trp Gln Ser Ile Asp Phe225 230 235 240Lys Gln Val Leu His Ser Trp Phe Arg Gln Pro Gln Ser Asn Trp Gly245 250 255Ile Glu Ile Asn Ala Phe Asp Pro Ser Gly Thr Asp Leu Ala Val Thr260 265 270Ser Leu Gly Pro Gly Ala Glu Gly Leu His Pro Phe Met Glu Leu Arg275 280 285Val Leu Glu Asn Thr Lys Arg Ser Arg Arg Asn Leu Gly Leu Asp Cys290 295 300Asp Glu His Ser Ser Glu Ser Arg Cys Cys Arg Tyr Pro Leu Thr Val305 310 315 320Asp Phe Glu Ala Phe Gly Trp Asp Trp Ile Ile Ala Pro Lys Arg Tyr325 330 335Lys Ala Asn Tyr Cys Ser Gly Gln Cys Glu Tyr Met Phe Met Gln Lys340 345 350Tyr Pro His Thr His Leu Val Gln Gln Ala Asn Pro Arg Gly Ser Ala355 360 365Gly Pro Cys Cys Thr Pro Thr Lys Met Ser Pro Ile Asn Met Leu Tyr370 375 380Phe Asn Asp Lys Gln Gln Ile Ile Tyr Gly Lys Ile Pro Gly Met Val385 390 395 400Val Asp Arg Cys Gly Cys Ser405<210>35<211>1456<212>DNA<213>智人(Homo sapiens)<400>35cccggagcca cggagcccgc gccgcccgcc cgcccggccc acggagccca tggacctgag 60cgccgccgcc gcgctgtgcc tttggctgct gagcgcctgc cgcccccgcg acgggctgga120agcggccgcc gtgctgcgag cggcgggggc tgggccggtc cggagcccag ggggcggcgg180cggcggcggc ggcggcggcg gcggcgggcg gactcttgcc caggctgcgg gcgccgcggc240tgtcccggcc gccgcggttc cccgggcccg cgccgcgcgc cgcgccgcgg gctccggctt300caggaacggc tcggtggtgc cgcaccactt catgatgtcg ctttaccgga gcctggccgg360gagggctccg gccggggcag ccgctgtctc cgcctcgggc catggtcgcg cggacacgat420caccggcttc acagaccagg cgacccaaga cgaatcggca gccgaaacag gccagagctt480cctgttcgac gtgtccagcc ttaacgacgc agacgaggtg gtgggtgccg agctgcgcgt540gctgcgccgg ggatctccag agtcgggccc aggcagctgg acttctccgc cgttgctgct600
gctgtccacg tgcccgggcg ccgcccgagc gccacgcctg ctgtactcgc gggcagctga 660gcccctagtc ggtcagcgct gggaggcgtt cgacgtggcg gacgccatga ggcgccaccg 720tcgtgaaccg cgcccccccc gcgcgttctg cctcttgctg cgcgcagtgg caggcccggt 780gccgagcccg ttggcactgc ggcgactggg cttcggctgg ccgggcggag ggggctctgc 840ggcagaggag cgcgcggtgc tagtcgtctc ctcccgcacg cagaggaaag agagcttatt 900ccgggagatc cgcgcccagg cccgcgcgct cggggccgct ctggcctcag agccgctgcc 960cgacccagga accggcaccg cgtcgccaag ggcagtcatt ggcggccgca gacggaggag 1020gacggcgttg gccgggacgc ggacagcgca gggcagcggc gggggcgcgg gccggggcca 1080cgggcgcagg ggccggagcc gctgcagccg caagccgttg cacgtggact tcaaggagct 1140cggctgggac gactggatca tcgcgccgct ggactacgag gcgtaccact gcgagggcct 1200ttgcgacttc cctttgcgtt cgcacctcga gcccaccaac catgccatca ttcagacgct 1260gctcaactcc atggcaccag acgcggcgcc ggcctcctgc tgtgtgccag cgcgcctcag 1320ccccatcagc atcctctaca tcgacgccgc caacaacgtt gtctacaagc aatacgagga 1380catggtggtg gaggcctgcg gctgcaggta gcgcgcgggc cggggagggg gcagccacgc 1440ggccgaggat ccccag 1456<210>36<211>453<212>PRT<213>智人(Homo sapiens)<400>36Met Asp Leu Ser Ala Ala Ala Ala Leu Cys Leu Trp Leu Leu Ser Ala1 5 10 15Cys Arg Pro Arg Asp Gly Leu Glu Ala Ala Ala Val Leu Arg Ala Ala20 25 30Gly Ala Gly Pro Val Arg Ser Pro Gly Gly Gly Gly Gly Gly Gly Gly35 40 45Gly Gly Gly Gly Gly Arg Thr Leu Ala Gln Ala Ala Gly Ala Ala Ala50 55 60Val Pro Ala Ala Ala Val Pro Arg Ala Arg Ala Ala Arg Arg Ala Ala65 70 75 80Gly Ser Gly Phe Arg Asn Gly Ser Val Val Pro His His Phe Met Met85 90 95Ser Leu Tyr Arg Ser Leu Ala Gly Arg Ala Pro Ala Gly Ala Ala Ala100 105 110Val Ser Ala Ser Gly His Gly Arg Ala Asp Thr Ile Thr Gly Phe Thr115 120 125Asp Gln Ala Thr Gln Asp Glu Ser Ala Ala Glu Thr Gly Gln Ser Phe130 135 140Leu Phe Asp Val Ser Ser Leu Asn Asp Ala Asp Glu Val Val Gly Ala145 150 155 160
Glu Leu Arg Val Leu Arg Arg Gly Ser Pro Glu Ser Gly Pro Gly Ser165 170 175Trp Thr Ser Pro Pro Leu Leu Leu Leu Ser Thr Cys Pro Gly Ala Ala180 185 190Arg Ala Pro Arg Leu Leu Tyr Ser Arg Ala Ala Glu Pro Leu Val Gly195 200 205Gln Arg Trp Glu Ala Phe Asp Val Ala Asp Ala Met Arg Arg His Arg210 215 220Arg Glu Pro Arg Pro Pro Arg Ala Phe Cys Leu Leu Leu Arg Ala Val225 230 235 240Ala Gly Pro Val Pro Ser Pro Leu Ala Leu Arg Arg Leu Gly Phe Gly245 250 255Trp Pro Gly Gly Gly Gly Ser Ala Ala Glu Glu Arg Ala Val Leu Val260 265 270Val Ser Ser Arg Thr Gln Arg Lys Glu Ser Leu Phe Arg Glu Ile Arg275 280 285Ala Gln Ala Arg Ala Leu Gly Ala Ala Leu Ala Ser Glu Pro Leu Pro290 295 300Asp Pro Gly Thr Gly Thr Ala Ser Pro Arg Ala Val Ile Gly Gly Arg305 310 315 320Arg Arg Arg Arg Thr Ala Leu Ala Gly Thr Arg Thr Ala Gln Gly Ser325 330 335Gly Gly Gly Ala Gly Arg Gly His Gly Arg Arg Gly Arg Ser Arg Cys340 345 350Ser Arg Lys Pro Leu His Val Asp Phe Lys Glu Leu Gly Trp Asp Asp355 360 365Trp Ile Ile Ala Pro Leu Asp Tyr Glu Ala Tyr His Cys Glu Gly Leu370 375 380Cys Asp Phe Pro Leu Arg Ser His Leu Glu Pro Thr Asn His Ala Ile385 390 395 400Ile Gln Thr Leu Leu Asn Ser Met Ala Pro Asp Ala Ala Pro Ala Ser405 410 415Cys Cys Val Pro Ala Arg Leu Ser Pro Ile Ser Ile Leu Tyr Ile Asp420 425 430Ala Ala Asn Asn Val Val Tyr Lys Gln Tyr Glu Asp Met Val Val Glu
435 440 445Ala Cys Gly Cys Arg450<210>37<211>4561<212>DNA<213>智人(Homo sapiens)<400>37atggatactc ccagggtcct gctctcggcc gtcttcctca tcagttttct gtgggatttg 60cccggtttcc agcaggcttc catctcatcc tcctcgtcgt ccgccgagct gggttccacc 120aagggcatgc gaagccgcaa ggaaggcaag atgcagcggg cgccgcgcga cagtgacgcg 180ggccgggagg gccaggaacc acagccgcgg cctcaggacg aaccccgggc tcagcagccc 240cgggcgcagg agccgccagg caggggtccg cgcgtggtgc cccacgagta catgctgtca 300atctacagga cttactccat cgctgagaag ctgggcatca atgccagctt tttccagtct 360tccaagtcgg ctaatacgat caccagcttt gtagacaggg gactagcctc cccaccccca 420tccccgccac tgcgctgtat gcccccgatc ctggagatag aggagggatt gcatgtgcac 480ccagtctggg gaggcctctg ttcccgagcc aaggcctcca gactagcagg accgagatcc 540acaagtaccg ctacaacccc ggaatgcggt ggagggctgg ggatgcgagc ggtccacagc 600gggaggagac gctgcatgac cacccggaca gcatcttcaa aggcgctgtc tcctccgcgt 660ctccgggttc tcagaaaatg cgaagaaagg cagttcgttg actgggaagg cgccttcgtg 720gaggacctgg ttgctcccct gggctcccgg gtgacttacc ggtcgacagt gcagggaagg 780ccgcccctag ccaacccccc agagacaaaa ggagtttcct taaagcgcct tggagctcct 840gataggactg gccctgtggt cagatcgtgc ccccacaaaa ggacaccaaa gtggggaaag 900aaacgaatcc ttaggcctct cagggctgca ctgccagcca gggagtcatt tgggttagca 960caagggctgt cactggcctt gacccctgca gaagaggaaa cctgcaagaa gggctggatc1020cttgatgtgg ctggggtgga ggtcatctgt tcacctggca ctgtgggagg gacagcagtg1080gtgacagggc ctcacaggac tgagaagaat cgggatgatg agcacctttc ctccactcac1140ttctggaatc ttgtggagag aagtggacca caaggactga agtccagaga actggatttc1200aaaggaagtc aagagaagga cagctgccag gaaacgaaga taagccctaa tccagcaatt1260gtaactggaa atgtttatat gtctaatgtt cagcaaacac cgttaacaga ggtcagcagg1320cagcaggcaa agtgtcttca gggtaacagt gcatggtgtt gtattcactc cccaggttgg1380atgcctcctc tgagctattt ctgtgatgca ggtttagaca ggttggggca tgtgcgtaag1440agtgaaccag ccagtgctac ggtcagcccc gagtacaaac tgggtgtggc agaggctcca1500gagccagtgc ccccgggcta catctggact gacgatctct cgcacactcc tctccggaga1560cagaagtatt tgtttgatgt gtccatgctc tcagacaaag aagagctggt gggcgcggag1620ctgcggctct ttcgccaggc gccctcagcg ccctgggggc caccagccgg gccgctccac1680gtgcagctct tcccttgcct ttcgccccta ctgctggacg cgcggaccct ggacccgcag1740ggggcgccgc cggccggctg ggaagtcttc gacgtgtggc agggcctgcg ccaccagccc1800tggaagcagc tgtgcttgga gctgcgggcc gcatggggcg agctggacgc cggggaggcc1860gaggcgcgcg cgcggggacc ccagcaaccg ccgcccccgg acctgcggag tctgggcttc1920ggccggaggg tgcggcctcc ccaggagcgg gccctgctgg tggtattcac cagatcccag1980cgcaagaacc tgttcgcaga gatgcgcgag cagctgggct cggccgaggc tgcgggcccg2040ggcgcgggcg ccgaggggtc gtggccgccg ccgtcgggcg ccccggatgc caggccttgg2100ctgccctcgc ccggccgccg gcggcggcgc acggccttcg ccagtcgcca tggcaagcgg2160cacggcaaga agtccaggct acgctgcagc aagaagcccc tgcacgtgaa cttcaaggag2220ctgggctggg acgactggat tatcgcgccc ctggagtacg aggcctatca ctgcgagggt2280gtatgcgact tcccgctgcg ctcgcacctg gagcccacca accacgccat catccagacg2340ctgatgaact ccatggaccc cggctccacc ccgcccagct gctgcgtgcc caccaaattg2400actcccatca gcattctata catcgacgcg ggcaataatg tggtctacaa gcagtacgag2460
gacatggtgg tggagtcgtg cggctgcagg tagcggtgcc tttcccgccg ccttggcccg 2520gaaccaaggt gggccaaggt ccgccttgca ggggaggcct ggctgcagag aggcggagga 2580ggaagctggc gctgggggag gctgagggtg agggaacagc ctggatgtga gagccggtgg 2640gagagaaggg agcgcagcct tcccagtaac ttctacctgc cagcccagag ggaaatatgg 2700attttcacac cttgcctggc caccctggaa aaacaagcca aggaggattt cttttgttct 2760gttttctctc tctctctctc tctctctctc tctctctctc tctctctctc tattactgtg 2820gctttggatt tccttatgtg tcttacaggc tttgatagaa ggggagggga ggagagatgc 2880atacccgttt ctcaactgct ccatggattg aaaaaataac agtttaaaaa gggaaacaat 2940gtgggaggaa gaatcaccgt tgacgcatct tgatttggtt ggtttttaca tgtgtaaaga 3000aggtggggtc tctggccatg tcatagccca tgtcttgtgc cctcccacac agaaagtgtt 3060agatagggaa attggcaaaa agaatagtta agtcaggaat ggtcctgcct atagaagagc 3120tttgagagag gtgggcccac gggtgcccct ctcacccatt tgtgtactct gtgagtttac 3180cagctctgcc ctggcctctt tcggtaccag gaactggcaa ccttcatctc actcctgagg 3240gcccaggtct ctgccttcat tgttgctttt tctggtgggg gcaaggggag ctggtatgga 3300tggaatgaca agaattagtc caaatggaac cccttgaagg ataatgagaa accacaaggc 3360ctgcctctga ctggggctga cacggaggtg cattagccca ggctggaggt agcccaccca 3420aatgcccttt ctgattctaa ttgatttctt tcaacagaat ttgccaaaat tcagacatgc 3480acttctaagg ggaaggtgat tttccagttc aaaaaaatgg gcaggagtgg ggaacaaaac 3540aattaacgta agagctacaa aggagggaaa aggaaccaag aagtagaagg agtcccatca 3600ggagggaaga tggtgggcct cagggaggat ggggatcaag ggacaggcca ggagccagga 3660gtggggaagg gagggatgaa aggggacaca agtccctgtc tctgaagttt ctttaaaatc 3720tgagttccct cccctctctt tgacattcct gaaagattac cagccagcaa tagcccaggg 3780ctcccccaaa agaattggtt cagattgtaa ttatcagtta ggcaatgttt ttaaaactta 3840gtaatgagaa actgtgaaaa gagccaagtg ttacattgag cttggggtgg gagatgggga 3900acaggcagtg aggaaggaga caggggtgga attcgtcttc tgggaggaag ctggagagag 3960cacagtgaaa ttgaaatacc cattcccaga tagtcaaaaa catgaacttt cccccagcct 4020gcaccagtat tgttttcaaa cattgcccat gagtaggccc tttgaagagt tagcttcctc 4080ctcatctttg actataaaat tgtttaatca atggaatttg taccagcctt ttaaaaagtt 4140ttagtttttc ctaagtgatt ttgctctctt ccaatctaaa cctgttgctt gtttggttca 4200gagaactaca aactgtcaaa gaaagggtgg ggatgataag aaatgctaat ataaaaatgc 4260taagtgaaaa aaagacttgg ccaggagaaa taatttaaaa tgcacatttg ctttggatgc 4320actgttgttc tgttaaggct gtatatattt gtttatttaa ggtgactgaa agtgcaaaga 4380ggaaatggac agcatgcaat tcatcctaat gtacaaaacg ttatatgcac tcaaatgtta 4440taatttctaa tatttttaaa gtttatattc gagttgtaca aagttaagca ttaatcagat 4500atttcatttt ttcataatgt taccattttc ttaaatatta ttacaaaatt ttaagtctgt 4560c 4561<210>38<211>830<212>PRT<213>智人(Homo sapiens)<400>38Met Asp Thr Pro Arg Val Leu Leu Ser Ala Val Phe Leu Ile Ser Phe1 5 10 15Leu Trp Asp Leu Pro Gly Phe Gln Gln Ala Ser Ile Ser Ser Ser Ser20 25 30Ser Ser Ala Glu Leu Gly Ser Thr Lys Gly Met Arg Ser Arg Lys Glu35 40 45
Gly Lys Met Gln Arg Ala Pro Arg Asp Ser Asp Ala Gly Arg Glu Gly50 55 60Gln Glu Pro Gln Pro Arg Pro Gln Asp Glu Pro Arg Ala Gln Gln Pro65 70 75 80Arg Ala Gln Glu Pro Pro Gly Arg Gly Pro Arg Val Val Pro His Glu85 90 95Tyr Met Leu Ser Ile Tyr Arg Thr Tyr Ser Ile Ala Glu Lys Leu Gly100 105 110Ile Asn Ala Ser Phe Phe Gln Ser Ser Lys Ser Ala Asn Thr Ile Thr115 120 125Ser Phe Val Asp Arg Gly Leu Ala Ser Pro Pro Pro Ser Pro Pro Leu130 135 140Arg Cys Met Pro Pro Ile Leu Glu Ile Glu Glu Gly Leu His Val His145 150 155 160Pro Val Trp Gly Gly Leu Cys Ser Arg Ala Lys Ala Ser Arg Leu Ala165 170 175Gly Pro Arg Ser Thr Ser Thr Ala Thr Thr Pro Glu Cys Gly Gly Gly180 185 190Leu Gly Met Arg Ala Val His Ser Gly Arg Arg Arg Cys Met Thr Thr195 200 205Arg Thr Ala Ser Ser Lys Ala Leu Ser Pro Pro Arg Leu Arg Val Leu210 215 220Arg Lys Cys Glu Glu Arg Gln Phe Val Asp Trp Glu Gly Ala Phe Val225 230 235 240Glu Asp Leu Val Ala Pro Leu Gly Ser Arg Val Thr Tyr Arg Ser Thr245 250 255Val Gln Gly Arg Pro Pro Leu Ala Asn Pro Pro Glu Thr Lys Gly Val260 265 270Ser Leu Lys Arg Leu Gly Ala Pro Asp Arg Thr Gly Pro Val Val Arg275 280 285Ser Cys Pro His Lys Arg Thr Pro Lys Trp Gly Lys Lys Arg Ile Leu290 295 300Arg Pro Leu Arg Ala Ala Leu Pro Ala Arg Glu Ser Phe Gly Leu Ala305 310 315 320Gln Gly Leu Ser Leu Ala Leu Thr Pro Ala Glu Glu Glu Thr Cys Lys
325 330 335Lys Gly Trp Ile Leu Asp Val Ala Gly Val Glu Val Ile Cys Ser Pro340 345 350Gly Thr Val Gly Gly Thr Ala Val Val Thr Gly Pro His Arg Thr Glu355 360 365Lys Asn Arg Asp Asp Glu His Leu Ser Ser Thr His Phe Trp Asn Leu370 375 380Val Glu Arg Ser Gly Pro Gln Gly Leu Lys Ser Arg Glu Leu Asp Phe385 390 395 400Lys Gly Ser Gln Glu Lys Asp Ser Cys Gln Glu Thr Lys Ile Ser Pro405 410 415Asn Pro Ala Ile Val Thr Gly Asn Val Tyr Met Ser Asn Val Gln Gln420 425 430Thr Pro Leu Thr Glu Val Ser Arg Gln Gln Ala Lys Cys Leu Gln Gly435 440 445Asn Ser Ala Trp Cys Cys Ile His Ser Pro Gly Trp Met Pro Pro Leu450 455 460Ser Tyr Phe Cys Asp Ala Gly Leu Asp Arg Leu Gly His Val Arg Lys465 470 475 480Ser Glu Pro Ala Ser Ala Thr Val Ser Pro Glu Tyr Lys Leu Gly Val485 490 495Ala Glu Ala Pro Glu Pro Val Pro Pro Gly Tyr Ile Trp Thr Asp Asp500 505 510Leu Ser His Thr Pro Leu Arg Arg Gln Lys Tyr Leu Phe Asp Val Ser515 520 525Met Leu Ser Asp Lys Glu Glu Leu Val Gly Ala Glu Leu Arg Leu Phe530 535 540Arg Gln Ala Pro Ser Ala Pro Trp Gly Pro Pro Ala Gly Pro Leu His545 550 555 560Val Gln Leu Phe Pro Cys Leu Ser Pro Leu Leu Leu Asp Ala Arg Thr565 570 575Leu Asp Pro Gln Gly Ala Pro Pro Ala Gly Trp Glu Val Phe Asp Val580 585 590Trp Gln Gly Leu Arg His Gln Pro Trp Lys Gln Leu Cys Leu Glu Leu595 600 605
Arg Ala Ala Trp Gly Glu Leu Asp Ala Gly Glu Ala Glu Ala Arg Ala610 615 620Arg Gly Pro Gln Gln Pro Pro Pro Pro Asp Leu Arg Ser Leu Gly Phe625 630 635 640Gly Arg Arg Val Arg Pro Pro Gln Glu Arg Ala Leu Leu Val Val Phe645 650 655Thr Arg Ser Gln Arg Lys Asn Leu Phe Ala Glu Met Arg Glu Gln Leu660 665 670Gly Ser Ala Glu Ala Ala Gly Pro Gly Ala Gly Ala Glu Gly Ser Trp675 680 685Pro Pro Pro Ser Gly Ala Pro Asp Ala Arg Pro Trp Leu Pro Ser Pro690 695 700Gly Arg Arg Arg Arg Arg Thr Ala Phe Ala Ser Arg His Gly Lys Arg705 710 715 720His Gly Lys Lys Ser Arg Leu Arg Cys Ser Lys Lys Pro Leu His Val725 730 735Asn Phe Lys Glu Leu Gly Trp Asp Asp Trp Ile Ile Ala Pro Leu Glu740 745 750Tyr Glu Ala Tyr His Cys Glu Gly Val Cys Asp Phe Pro Leu Arg Ser755 760 765His Leu Glu Pro Thr Asn His Ala Ile Ile Gln Thr Leu Met Asn Ser770 775 780Met Asp Pro Gly Ser Thr Pro Pro Ser Cys Cys Val Pro Thr Lys Leu785 790 795 800Thr Pro Ile Ser Ile Leu Tyr Ile Asp Ala Gly Asn Asn Val Val Tyr805 810 815Lys Gln Tyr Glu Asp Met Val Val Glu Ser Cys Gly Cys Arg820 825 830<210>39<211>1179<212>DNA<213>智人(Homo sapiens)<400>39atggtcctcc tcagtattct tagaattctt tttctttgtg aactcgtgct tttcatggaa 60cacagggccc aaatggcaga aggagggcag tcctctattg cccttctggc tgaggcccct120actttgcccc tgattgagga gctgctagaa gaatcccctg gcgaacagcc aaggaagccc180
cggctcctag ggcattcact gcggtacatg ctggagttgt accggcgttc agctgactcg240catgggcacc ctagagagaa ccgcaccatt ggggccacca tggtgaggct ggtgaagccc300ttgaccagtg tggcaaggcc tcacagaggt acctggcata tacagatcct gggctttcct360ctcagaccaa accgaggact ataccaacta gttagagcca ctgtggttta ccgccatcat420ctccaactaa ctcgcttcaa tctctcctgc catgtggagc cctgggtgca gaaaaaccca480accaaccact tcccttcctc agaaggagat tcctcaaaac cttccctgat gtctaacgct540tggaaagaga tggatatcac acaacttgtt cagcaaaggt tctggaataa caagggacac600aggatcctac gactccgttt tatgtgtcag cagcaaaaag atagtggtgg tcttgagctc660tggcatggca cttcatcctt ggacattgcc ttcttgttac tctatttcaa tgatactcat720aaaagcattc ggaaggctaa atttcttccc aggggcatgg aggagttcat ggaaagggaa780tctcttctcc ggagaacccg acaagcagat ggtatctcag ctgaggttac tgcctcttcc840tcaaaacata gcgggcctga aaataaccag tgttccctcc accctttcca aatcagcttc900cgccagctgg gttgggatca ctggatcatt gctccccctt tctacacccc aaactactgt960aaaggaactt gtctccgagt actacgcgat ggtctcaatt cccccaatca cgccattatt 1020cagaacctta tcaatcagtt ggtggaccag agtgtccccc ggccctcctg tgtcccgtat 1080aagtatgttc caattagtgt ccttatgatt gaggcaaatg ggagtatttt gtacaaggag 1140tatgagggta tgattgctga gtcttgtaca tgcagatga 1179<210>40<21l>392<212>PRT<213>智人(Homo sapiens)<400>40Met Val Leu Leu Ser Ile Leu Arg Ile Leu Phe Leu Cys Glu Leu Val1 5 10 15Leu Phe Met Glu His Arg Ala Gln Met Ala Glu Gly Gly Gln Ser Ser20 25 30Ile Ala Leu Leu Ala Glu Ala Pro Thr Leu Pro Leu Ile Glu Glu Leu35 40 45Leu Glu Glu Ser Pro Gly Glu Gln Pro Arg Lys Pro Arg Leu Leu Gly50 55 60His Ser Leu Arg Tyr Met Leu Glu Leu Tyr Arg Arg Ser Ala Asp Ser65 70 75 80His Gly His Pro Arg Glu Asn Arg Thr Ile Gly Ala Thr Met Val Arg85 90 95Leu Val Lys Pro Leu Thr Ser Val Ala Arg Pro His Arg Gly Thr Trp100 105 110His Ile Gln Ile Leu Gly Phe Pro Leu Arg Pro Asn Arg Gly Leu Tyr115 120 125Gln Leu Val Arg Ala Thr Val Val Tyr Arg His His Leu Gln Leu Thr130 135 140Arg Phe Asn Leu Ser Cys His Val Glu Pro Trp Val Gln Lys Asn Pro
145 150 155 160Thr Asn His Phe Pro Ser Ser Glu Gly Asp Ser Ser Lys Pro Ser Leu165 170 175Met Ser Asn Ala Trp Lys Glu Met Asp Ile Thr Gln Leu Val Gln Gln180 185 190Arg Phe Trp Asn Asn Lys Gly His Arg Ile Leu Arg Leu Arg Phe Met195 200 205Cys Gln Gln Gln Lys Asp Ser Gly Gly Leu Glu Leu Trp His Gly Thr210 215 220Ser Ser Leu Asp Ile Ala Phe Leu Leu Leu Tyr Phe Asn Asp Thr His225 230 235 240Lys Ser Ile Arg Lys Ala Lys Phe Leu Pro Arg Gly Met Glu Glu Phe245 250 255Met Glu Arg Glu Ser Leu Leu Arg Arg Thr Arg Gln Ala Asp Gly Ile260 265 270Ser Ala Glu Val Thr Ala Ser Ser Ser Lys His Ser Gly Pro Glu Asn275 280 285Asn Gln Cys Ser Leu His Pro Phe Gln Ile Ser Phe Arg Gln Leu Gly290 295 300Trp Asp His Trp Ile Ile Ala Pro Pro Phe Tyr Thr Pro Asn Tyr Cys305 310 315 320Lys Gly Thr Cys Leu Arg Val Leu Arg Asp Gly Leu Asn Ser Pro Asn325 330 335His Ala Ile Ile Gln Asn Leu Ile Asn Gln Leu Val Asp Gln Ser Val340 345 350Pro Arg Pro Ser Cys Val Pro Tyr Lys Tyr Val Pro Ile Ser Val Leu355 360 365Met Ile Glu Ala Asn Gly Ser Ile Leu Tyr Lys Glu Tyr Glu Gly Met370 375 380Ile Ala Glu Ser Cys Thr Cys Arg385 390<210>41<211>375<212>DNA<213>智人(Homo sapiens)
<400>41caagcagatg gtatctcagc tgaggttact gcctcttcct caaaacatag cgggcctgaa 60aataaccagt gttccctcca ccctttccaa atcagcttcc gccagctggg ttgggatcac 120tggatcattg ctcccccttt ctacacccca aactactgta aaggaacttg tctccgagta 180ctacgcgatg gtctcaattc ccccaatcac gccattattc agaaccttat caatcagttg 240gtggaccaga gtgtcccccg gccctcctgt gtcccgtata agtatgttcc aattagtgtc 300cttatgattg aggcaaatgg gagtattttg tacaaggagt atgagggtat gattgctgag 360tcttgtacat gcaga 375<210>42<211>125<212>PRT<213>智人(Homo sapiens)<400>42Gln Ala Asp Gly Ile Ser Ala Glu Val Thr Ala Ser Ser Ser Lys His1 5 10 15Ser Gly Pro Glu Asn Asn Gln Cys Ser Leu His Pro Phe Gln Ile Ser20 25 30Phe Arg Gln Leu Gly Trp Asp His Trp Ile Ile Ala Pro Pro Phe Tyr35 40 45Thr Pro Asn Tyr Cys Lys Gly Thr Cys Leu Arg Val Leu Arg Asp Gly50 55 60Leu Asn Ser Pro Asn His Ala Ile Ile Gln Asn Leu Ile Asn Gln Leu65 70 75 80Val Asp Gln Ser Val Pro Arg Pro Ser Cys Val Pro Tyr Lys Tyr Val85 90 95Pro Ile Ser Val Leu Met Ile Glu Ala Asn Gly Ser Ile Leu Tyr Lys100 105 110Glu Tyr Glu Gly Met Ile Ala Glu Ser Cys Thr Cys Arg115 120 125<210>43<211>1744<212>DNA<213>智人(Homo sapiens)<400>43atgcacgccc actgcctgcc cttccttctg cacgcctggt gggccctact ccaggcgggt60gctgcgacgg tggccactgc gctcctgcgt acgcgggggc agccctcgtc gccatcccct 120ctggcgtaca tgctgagcct ctaccgcgac ccgctgccga gggcagacat catccgcagc 180ctacaggcag aagatgtggc agtggatggg cagaactgga cgtttgcttt tgacttctcc 240ttcctgagcc aacaagagga tctggcatgg gctgagctcc ggctgcagct gtccagccct 300gtggacctcc ccactgaggg ctcacttgcc attgagattt tccaccagcc aaagcccgac 360acagagcagg cttcagacag ctgcttagag cggtttcaga tggacctatt cactgtcact 420
ttgtcccagg tcaccttttc cttgggcagc atggttttgg aggtgaccag gcctctctcc480aagtggctga agcgccctgg ggccctggag aagcagatgt ccagggtagc tggagagtgc540tggccgcggc cccccacacc gcctgccacc aatgtgctcc ttatgctcta ctccaacctc600tcgcaggagc agaggcagct gggtgggtcc accttgctgt gggaagccga gagctcctgg660cgggcccagg agggacagct gtcctgggag tggggcaaga ggcaccgtcg acatcacttg720ccagacagaa gtcaactgtg tcggaaggtc aagttccagg tggacttcaa cctgatcgga780tggggctcct ggatcatcta ccccaagcag tacaacgcct atcgctgtga gggcgagtgt840cctaatcctg ttggggagga gtttcatccg accaaccatg catacatcca gagtctgctg900aaacgttacc agccccaccg agtcccttcc acttgttgtg ccccagtgaa gaccaagccg960c tgagcatgc tgtatgtgga taatggcaga gtgctcctag atcaccataa agacatgatc 1020gtggaagaat gtgggtgcct ctgatgacat cctggaggga gactggattt gcctgcactc 1080tggaaggctg ggaaactcct ggaagacatg ataaccatct aatccagtaa ggagaaacag 1140agaggggcaa agttgctctg cccaccagaa ctgaagagga ggggctgccc actctgtaaa 1200tgaagggctc agtggagtct ggccaagcac agaggctgct gtcaggaaga gggaggaaga 1260agcctgtgca gggggctggc tggatgttct ctttactgaa aagacagtgg caaggaaaag 1320cacaagtgca tgagttcttt actggatttt ttaaaaacct gtgaaccccc cgaaactgta 1380tgtgaaagtt gagacatatg tgcatgtatt ttggaggtgg gatgaagtca cctatagctt 1440tcatgtattc tccaaagtag tctgtgtgtg acctgtcccc ctccccaaag attaaggatc 1500actgtataga ttaaaaagag tccgtcaatc tcattgcctc aggctgggtt gggggagccc 1560cacagctttc tggctggcca gtggcaatct actggccttg tccagaggct cactggagtg 1620gttctctgct aatgagctgt acaacaataa agccattgtc tagttaaaaa aaaaaaaaaa 1680aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1740aaaa1744<210>44<211>347<212>PRT<213>智人(Homo sapiens)<400>44Met His Ala His Cys Leu Pro Phe Leu Leu His Ala Trp Trp Ala Leu1 5 10 15Leu Gln Ala Gly Ala Ala Thr Val Ala Thr Ala Leu Leu Arg Thr Arg20 25 30Gly Gln Pro Ser Ser Pro Ser Pro Leu Ala Tyr Met Leu Ser Leu Tyr35 40 45Arg Asp Pro Leu Pro Arg Ala Asp Ile Ile Arg Ser Leu Gln Ala Glu50 55 60Asp Val Ala Val Asp Gly Gln Asn Trp Thr Phe Ala Phe Asp Phe Ser65 70 75 80Phe Leu Ser Gln Gln Glu Asp Leu Ala Trp Ala Glu Leu Arg Leu Gln85 90 95Leu Ser Ser Pro Val Asp Leu Pro Thr Glu Gly Ser Leu Ala Ile Glu100 105 110Ile Phe His Gln Pro Lys Pro Asp Thr Glu Gln Ala Ser Asp Ser Cys
115 120 125Leu Glu Arg Phe Gln Met Asp Leu Phe Thr Val Thr Leu Ser Gln Val130 135 140Thr Phe Ser Leu Gly Ser Met Val Leu Glu Val Thr Arg Pro Leu Ser145 150 155 160Lys Trp Leu Lys Arg Pro Gly Ala Leu Glu Lys Gln Met Ser Arg Val165 170 175Ala Gly Glu Cys Trp Pro Arg Pro Pro Thr Pro Pro Ala Thr Asn Val180 185 190Leu Leu Met Leu Tyr Ser Asn Leu Ser Gln Glu Gln Arg Gln Leu Gly195 200 205Gly Ser Thr Leu Leu Trp Glu Ala Glu Ser Ser Trp Arg Ala Gln Glu210 215 220Gly Gln Leu Ser Trp Glu Trp Gly Lys Arg His Arg Arg His His Leu225 230 235 240Pro Asp Arg Ser Gln Leu Cys Arg Lys Val Lys Phe Gln Val Asp Phe245 250 255Asn Leu Ile Gly Trp Gly Ser Trp Ile Ile Tyr Pro Lys Gln Tyr Asn260 265 270Ala Tyr Arg Cys Glu Gly Glu Cys Pro Asn Pro Val Gly Glu Glu Phe275 280 285His Pro Thr Asn His Ala Tyr Ile Gln Ser Leu Leu Lys Arg Tyr Gln290 295 300Pro His Arg Val Pro Ser Thr Cys Cys Ala Pro Val Lys Thr Lys Pro305 310 315 320Leu Ser Met Leu Tyr Val Asp Asn Gly Arg Val Leu Leu Asp His His325 330 335Lys Asp Met Ile Val Glu Glu Cys Gly Cys Leu340 345<210>45<211>504<212>DNA<213>智人(Homo sapiens)<400>45tggccgcggc cccccacacc gcctgccacc aatgtgctcc ttatgctcta ctccaacctc 60tcgcaggagc agaggcagct gggtgggtcc accttgctgt gggaagccga gagctcctgg120
cgggcccagg agggacagct gtcctgggag tggggcaaga ggcaccgtcg acatcacttg180ccagacagaa gtcaactgtg tcggaaggtc aagttccagg tggacttcaa cctgatcgga240tggggctcct ggatcatcta ccccaagcag tacaacgcct atcgctgtga gggcgagtgt300cctaatcctg ttggggagga gtttcatccg accaaccatg catacatcca gagtctgctg360aaacgttacc agccccaccg agtcccttcc acttgttgtg ccccagtgaa gaccaagccg420ctgagcatgc tgtatgtgga taatggcaga gtgctcctag atcaccataa agacatgatc480gtggaagaat gtgggtgcct ctga 504<210>46<211>167<212>PRT<213>智人(Homo sapiens)<400>46Trp Pro Arg Pro Pro Thr Pro Pro Ala Thr Asn Val Leu Leu Met Leu1 5 10 15Tyr Ser Asn Leu Ser Gln Glu Gln Arg Gln Leu Gly Gly Ser Thr Leu20 25 30Leu Trp Glu Ala Glu Ser Ser Trp Arg Ala Gln Glu Gly Gln Leu Ser35 40 45Trp Glu Trp Gly Lys Arg His Arg Arg His His Leu Pro Asp Arg Ser50 55 60Gln Leu Cys Arg Lys Val Lys Phe Gln Val Asp Phe Asn Leu Ile Gly65 70 75 80Trp Gly Ser Trp Ile Ile Tyr Pro Lys Gln Tyr Asn Ala Tyr Arg Cys85 90 95Glu Gly Glu Cys Pro Asn Pro Val Gly Glu Glu Phe His Pro Thr Asn100 105 110His Ala Tyr Ile Gln Ser Leu Leu Lys Arg Tyr Gln Pro His Arg Val115 120 125Pro Ser Thr Cys Cys Ala Pro Val Lys Thr Lys Pro Leu Ser Met Leu130 135 140Tyr Val Asp Asn Gly Arg Val Leu Leu Asp His His Lys Asp Met Ile145 150 155 160Val Glu Glu Cys Gly Cys Leu165<210>47<211>1101<212>DNA<213>智人(Homo sapiens)
<400>47atgcagcccc tgtggctctg ctgggcactc tgggtgttgc ccctggccag ccccggggcc60gccctgaccg gggagcagct cctgggcagc ctgctgcggc agctgcagct caaagaggtg 120cccaccctgg acagggccga catggaggag ctggtcatcc ccacccacgt gagggcccag 180tacgtggccc tgctgcagcg cagccacggg gaccgctccc gcggaaagag gttcagccag 240agcttccgag aggtggccgg caggttcctg gcgttggagg ccagcacaca cctgctggtg 300ttcggcatgg agcagcggct gccgcccaac agcgagctgg tgcaggccgt gctgcggctc 360ttccaggagc cggtccccaa ggccgcgctg cacaggcacg ggcggctgtc cccgcgcagc 420gcccgggccc gggtgaccgt cgagtggctg cgcgtccgcg acgacggctc caaccgcacc 480tccctcatcg actccaggct ggtgtccgtc cacgagagcg gctggaaggc cttcgacgtg 540accgaggccg tgaacttctg gcagcagctg agccggcccc ggcagccgct gctgctacag 600gtgtcggtgc agagggagca tctgggcccg ctggcgtccg gcgcccacaa gctggtccgc 660tttgcctcgc agggggcgcc agccgggctt ggggagcccc agctggagct gcacaccctg 720gaccttgggg actatggagc tcagggcgac tgtgaccctg aagcaccaat gaccgagggc 780acccgctgct gccgccagga gatgtacatt gacctgcagg ggatgaagtg ggccgagaac 840tgggtgctgg agcccccggg cttcctggct tatgagtgtg tgggcacctg ccggcagccc 900ccggaggccc tggccttcaa gtggccgttt ctggggcctc gacagtgcat cgcctcggag 960actgcctcgc tgcccatgat cgtcagcatc aaggagggag gcaggaccag gccccaggtg 1020gtcagcctgc ccaacatgag ggtgcagaag tgcagctgtg cctcggatgg tgcgctcgtg 1080ccaaggaggc tccagccata g1101<210>48<211>366<212>PRT<213>智人(Homo sapiens)<400>48Met Gln Pro Leu Trp Leu Cys Trp Ala Leu Trp Val Leu Pro Leu Ala1 5 10 15Ser Pro Gly Ala Ala Leu Thr Gly Glu Gln Leu Leu Gly Ser Leu Leu20 25 30Arg Gln Leu Gln Leu Lys Glu Val Pro Thr Leu Asp Arg Ala Asp Met35 40 45Glu Glu Leu Val Ile Pro Thr His Val Arg Ala Gln Tyr Val Ala Leu50 55 60Leu Gln Arg Ser His Gly Asp Arg Ser Arg Gly Lys Arg Phe Ser Gln65 70 75 80Ser Phe Arg Glu Val Ala Gly Arg Phe Leu Ala Leu Glu Ala Ser Thr85 90 95His Leu Leu Val Phe Gly Met Glu Gln Arg Leu Pro Pro Asn Ser Glu100 105 110Leu Val Gln Ala Val Leu Arg Leu Phe Gln Glu Pro Val Pro Lys Ala115 120 125Ala Leu His Arg His Gly Arg Leu Ser Pro Arg Ser Ala Arg Ala Arg
130 135 140Val Thr Val Glu Trp Leu Arg Val Arg Asp Asp Gly Ser Asn Arg Thr145 150 155 160Ser Leu Ile Asp Ser Arg Leu Val Ser Val His Glu Ser Gly Trp Lys165 170 175Ala Phe Asp Val Thr Glu Ala Val Asn Phe Trp Gln Gln Leu Ser Arg180 185 190Pro Arg Gln Pro Leu Leu Leu Gln Val Ser Val Gln Arg Glu His Leu195 200 205Gly Pro Leu Ala Ser Gly Ala His Lys Leu Val Arg Phe Ala Ser Gln210 215 220Gly Ala Pro Ala Gly Leu Gly Glu Pro Gln Leu Glu Leu His Thr Leu225 230 235 240Asp Leu Gly Asp Tyr Gly Ala Gln Gly Asp Cys Asp Pro Glu Ala Pro245 250 255Met Thr Glu Gly Thr Arg Cys Cys Arg Gln Glu Met Tyr Ile Asp Leu260 265 270Gln Gly Met Lys Trp Ala Glu Asn Trp Val Leu Glu Pro Pro Gly Phe275 280 285Leu Ala Tyr Glu Cys Val Gly Thr Cys Arg Gln Pro Pro Glu Ala Leu290 295 300Ala Phe Lys Trp Pro Phe Leu Gly Pro Arg Gln Cys Ile Ala Ser Glu305 310 315 320Thr Ala Ser Leu Pro Met Ile Val Ser Ile Lys Glu Gly Gly Arg Thr325 330 335Arg Pro Gln Val Val Ser Leu Pro Asn Met Arg Val Gln Lys Cys Ser340 345 350Cys Ala Ser Asp Gly Ala Leu Val Pro Arg Arg Leu Gln Pro355 360 365<210>49<211>1098<212>DNA<213>智人(Homo sapiens)<400>49atgtggcccc tgtggctctg ctgggcactc tgggtgctgc ccctggctgg ccccggggcg60gccctgaccg aggagcagct cctgggcagc ctgctgcggc agctgcagct cagcgaggtg 120
cccgtactgg acagggccga catggagaag ctggtcatcc ccgcccacgt gagggcccag180tatgtagtcc tgctgcggcg cagccacggg gaccgctccc gcggaaagag gttcagccag240agcttccgag aggtggccgg caggttcctg gcgtcggagg ccagcacaca cctgctggtg300ttcggcatgg agcagcggct gccgcccaac agcgagctgg tgcaggccgt gctgcggctc360ttccaggagc cggtccccaa ggccgcgctg cacaggcacg ggcggctgtc cccgcgcagc420gcccaggccc gggtgaccgt cgagtggctg cgcgtccgcg acgacggctc caaccgcacc480tccctcatcg actccaggct ggtgtccgtc cacgagagcg gctggaaggc cttcgacgtg540accgaggccg tgaacttctg gcagcagctg agccggcccc ggcagccgct gctgctacag600gtgtcggtgc agagggagca tctgggcccg ctggcgtccg gcgcccacaa gctggtccgc660tttgcctcgc agggggcgcc agccgggctt ggggagcccc agctggagct gcacaccctg720gacctcaggg actatggagc tcagggcgac tgtgaccctg aagcaccaat gaccgagggc780acccgctgct gccgccagga gatgtacatt gacctgcagg ggatgaagtg ggccaagaac840tgggtgctgg agcccccggg cttcctggct tacgagtgtg tgggcacctg ccagcagccc900ccggaggccc tggccttcaa ttggccattt ctggggccgc gacagtgtat cgcctcggag960actgcctcgc tgcccatgat cgtcagcatc aaggagggag gcaggaggcc ccaggtggtc 1020agcctgccca acatgagggt gcagaagtgc agctgtgcct cggatggggc gctcgtgcca 1080aggaggctcc agccatag 1098<210>50<211>365<212>PRT<213>智人(Homo sapiens)<400>50Met Trp Pro Leu Trp Leu Cys Trp Ala Leu Trp Val Leu Pro Leu Ala1 5 10 15Gly Pro Gly Ala Ala Leu Thr Glu Glu Gln Leu Leu Gly Ser Leu Leu20 25 30Arg Gln Leu Gln Leu Ser Glu Val Pro Val Leu Asp Arg Ala Asp Met35 40 45Glu Lys Leu Val Ile Pro Ala His Val Arg Ala Gln Tyr Val Val Leu50 55 60Leu Arg Arg Ser His Gly Asp Arg Ser Arg Gly Lys Arg Phe Ser Gln65 70 75 80Ser Phe Arg Glu Val Ala Gly Arg Phe Leu Ala Ser Glu Ala Ser Thr85 90 95His Leu Leu Val Phe Gly Met Glu Gln Arg Leu Pro Pro Asn Ser Glu100 105 110Leu Val Gln Ala Val Leu Arg Leu Phe Gln Glu Pro Val Pro Lys Ala115 120 125Ala Leu His Arg His Gly Arg Leu Ser Pro Arg Ser Ala Gln Ala Arg130 135 140Val Thr Val Glu Trp Leu Arg Val Arg Asp Asp Gly Ser Asn Arg Thr
145 150 155 160Ser Leu Ile Asp Ser Arg Leu Val Ser Val His Glu Ser Gly Trp Lys165 170 175Ala Phe Asp Val Thr Glu Ala Val Asn Phe Trp Gln Gln Leu Ser Arg180 185 190Pro Arg Gln Pro Leu Leu Leu Gln Val Ser Val Gln Arg Glu His Leu195 200 205Gly Pro Leu Ala Ser Gly Ala His Lys Leu Val Arg Phe Ala Ser Gln210 215 220Gly Ala Pro Ala Gly Leu Gly Glu Pro Gln Leu Glu Leu His Thr Leu225 230 235 240Asp Leu Arg Asp Tyr Gly Ala Gln Gly Asp Cys Asp Pro Glu Ala Pro245 250 255Met Thr Glu Gly Thr Arg Cys Cys Arg Gln Glu Met Tyr Ile Asp Leu260 265 270Gln Gly Met Lys Trp Ala Lys Asn Trp Val Leu Glu Pro Pro Gly Phe275 280 285Leu Ala Tyr Glu Cys Val Gly Thr Cys Gln Gln Pro Pro Glu Ala Leu290 295 300Ala Phe Asn Trp Pro Phe Leu Gly Pro Arg Gln Cys Ile Ala Ser Glu305 310 315 320Thr Ala Ser Leu Pro Met Ile Val Ser Ile Lys Glu Gly Gly Arg Arg325 330 335Pro Gln Val Val Ser Leu Pro Asn Met Arg Val Gln Lys Cys Ser Cys340 345 350Ala Ser Asp Gly Ala Leu Val Pro Arg Arg Leu Gln Pro355 360 365<210>51<211>2291<212>DNA<213>智人(Homo sapiens)<400>51ctttccgccc cagccctgaa agcgttaacc ctggagcttt ctgcacaccc cccgaccgct 60cccgcccaag cttcctaaaa aagaaaggtg caaagtttgg tccaggatag aaaaatgact120gatcaaaggc aggcgatact tcctgttgcc gggacgctat atataacgtg atgagcgcac180gggctgcgga gacgcaccgg agcgctcgcc cagccgccgc ctccaagccc ctgaggtttc240cggggaccac aatgaacaag ttgctgtgct gcgcgctcgt gtttctggac atctccatta300
agtggaccac ccaggaaacg tttcctccaa agtaccttca ttatgacgaa gaaacctctc360atcagctgtt gtgtgacaaa tgtcctcctg gtacctacct aaaacaacac tgtacagcaa420agtggaagac cgtgtgcgcc ccttgccctg accactacta cacagacagc tggcacacca480gtgacgagtg tctatactgc agccccgtgt gcaaggagct gcagtacgtc aagcaggagt540gcaatcgcac ccacaaccgc gtgtgcgaat gcaaggaagg gcgctacctt gagatagagt600tctgcttgaa acataggagc tgccctcctg gatttggagt ggtgcaagct ggaaccccag660agcgaaatac agtttgcaaa agatgtccag atgggttctt ctcaaatgag acgtcatcta720aagcaccctg tagaaaacac acaaattgca gtgtctttgg tctcctgcta actcagaaag780gaaatgcaac acacgacaac atatgttccg gaaacagtga atcaactcaa aaatgtggaa840tagatgttac cctgtgtgag gaggcattct tcaggtttgc tgttcctaca aagtttacgc900ctaactggct tagtgtcttg gtagacaatt tgcctggcac caaagtaaac gcagagagtg960tagagaggat aaaacggcaa cacagctcac aagaacagac tttccagctg ctgaagttat 1020ggaaacatca aaacaaagac caagatatag tcaagaagat catccaagat attgacctct 1080gtgaaaacag cgtgcagcgg cacattggac atgctaacct caccttcgag cagcttcgta 1140gcttgatgga aagcttaccg ggaaagaaag tgggagcaga agacattgaa aaaacaataa 1200aggcatgcaa acccagtgac cagatcctga agctgctcag tttgtggcga ataaaaaatg 1260gcgaccaaga caccttgaag ggcctaatgc acgcactaaa gcactcaaag acgtaccact 1320ttcccaaaac tgtcactcag agtctaaaga agaccatcag gttccttcac agcttcacaa 1380tgtacaaatt gtatcagaag ttatttttag aaatgatagg taaccaggtc caatcagtaa 1440aaataagctg cttataactg gaaatggcca ttgagctgtt tcctcacaat tggcgagatc 1500ccatggatga gtaaactgtt tctcaggcac ttgaggcttt cagtgatatc tttctcatta 1560ccagtgacta attttgccac agggtactaa aagaaactat gatgtggaga aaggactaac 1620atctcctcca ataaacccca aatggttaat ccaactgtca gatctggatc gttatctact 1680gactatattt tcccttatta ctgcttgcag taattcaact ggaaattaaa aaaaaaaaac 1740tagactccat tgtgccttac taaatatggg aatgtctaac ttaaatagct ttgagatttc 1800agctatgcta gaggctttta ttagaaagcc atattttttt ctgtaaaagt tactaatata 1860tctgtaacac tattacagta ttgctattta tattcattca gatataagat ttgtacatat 1920tatcatccta taaagaaacg gtatgactta attttagaaa gaaaattata ttctgtttat 1980tatgacaaat gaaagagaaa atatatattt ttaatggaaa gtttgtagca tttttctaat 2040aggtactgcc atatttttct gtgtggagta tttttataat tttatctgta taagctgtaa 2100tatcatttta tagaaaatgc attatttagt caattgttta atgttggaaa acatatgaaa 2160tataaattat ctgaatatta gatgctctga gaaattgaat gtaccttatt taaaagattt 2220tatggtttta taactatata aatgacatta ttaaagtttt caaattattt tttaaaaaaa 2280aaaaaaaaaa a2291<210>52<211>401<212>PRT<213>智人(Homo sapiens)<400>52Met Asn Lys Leu Leu Cys Cys Ala Leu Val Phe Leu Asp Ile Ser Ile1 5 10 15Lys Trp Thr Thr Gln Glu Thr Phe Pro Pro Lys Tyr Leu His Tyr Asp20 25 30Glu Glu Thr Ser His Gln Leu Leu Cys Asp Lys Cys Pro Pro Gly Thr35 40 45Tyr Leu Lys Gln His Cys Thr Ala Lys Trp Lys Thr Val Cys Ala Pro50 55 60
Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His Thr Ser Asp Glu Cys65 70 75 80Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu Gln Tyr Val Lys Gln Glu85 90 95Cys Asn Arg Thr His Asn Arg Val Cys Glu Cys Lys Glu Gly Arg Tyr100 105 110Leu Glu Ile Glu Phe Cys Leu Lys His Arg Ser Cys Pro Pro Gly Phe115 120 125Gly Val Val Gln Ala Gly Thr Pro Glu Arg Asn Thr Val Cys Lys Arg130 135 140Cys Pro Asp Gly Phe Phe Ser Asn Glu Thr Ser Ser Lys Ala Pro Cys145 150 155 160Arg Lys His Thr Asn Cys Ser Val Phe Gly Leu Leu Leu Thr Gln Lys165 170 175Gly Asn Ala Thr His Asp Asn Ile Cys Ser Gly Asn Ser Glu Ser Thr180 185 190Gln Lys Cys Gly Ile Asp Val Thr Leu Cys Glu Glu Ala Phe Phe Arg195 200 205Phe Ala Val Pro Thr Lys Phe Thr Pro Asn Trp Leu Ser Val Leu Val210 215 220Asp Asn Leu Pro Gly Thr Lys Val Asn Ala Glu Ser Val Glu Arg Ile225 230 235 240Lys Arg Gln His Ser Ser Gln Glu Gln Thr Phe Gln Leu Leu Lys Leu245 250 255Trp Lys His Gln Asn Lys Asp Gln Asp Ile Val Lys Lys Ile Ile Gln260 265 270Asp Ile Asp Leu Cys Glu Asn Ser Val Gln Arg His Ile Gly His Ala275 280 285Asn Leu Thr Phe Glu Gln Leu Arg Ser Leu Met Glu Ser Leu Pro Gly290 295 300Lys Lys Val Gly Ala Glu Asp Ile Glu Lys Thr Ile Lys Ala Cys Lys305 310 315 320Pro Ser Asp Gln Ile Leu Lys Leu Leu Ser Leu Trp Arg Ile Lys Asn325 330 335
Gly Asp Gln Asp Thr Leu Lys Gly Leu Met His Ala Leu Lys His Ser340 345 350Lys Thr Tyr His Phe Pro Lys Thr Val Thr Gln Ser Leu Lys Lys Thr355 360 365Ile Arg Phe Leu His Ser Phe Thr Met Tyr Lys Leu Tyr Gln Lys Leu370 375 380Phe Leu Glu Met Ile Gly Asn Gln Val Gln Ser Val Lys Ile Ser Cys385 390 395 400Leu<210>53<211>1014<212>DNA<213>智人(Homo sapiens)<400>53ccttgccctg accactacta cacagacagc tggcacacca gtgacgagtg tctatactgc 60agccccgtgt gcaaggagct gcagtacgtc aagcaggagt gcaatcgcac ccacaaccgc120gtgtgcgaat gcaaggaagg gcgctacctt gagatagagt tctgcttgaa acataggagc180tgccctcctg gatttggagt ggtgcaagct ggaaccccag agcgaaatac agtttgcaaa240agatgtccag atgggttctt ctcaaatgag acgtcatcta aagcaccctg tagaaaacac300acaaattgca gtgtctttgg tctcctgcta actcagaaag gaaatgcaac acacgacaac360atatgttccg gaaacagtga atcaactcaa aaatgtggaa tagatgttac cctgtgtgag420gaggcattct tcaggtttgc tgttcctaca aagtttacgc ctaactggct tagtgtcttg480gtagacaatt tgcctggcac caaagtaaac gcagagagtg tagagaggat aaaacggcaa540cacagctcac aagaacagac tttccagctg ctgaagttat ggaaacatca aaacaaagac600caagatatag tcaagaagat catccaagat attgacctct gtgaaaacag cgtgcagcgg660cacattggac atgctaacct caccttcgag cagcttcgta gcttgatgga aagcttaccg720ggaaagaaag tgggagcaga agacattgaa aaaacaataa aggcatgcaa acccagtgac780cagatcctga agctgctcag tttgtggcga ataaaaaatg gcgaccaaga caccttgaag840ggcctaatgc acgcactaaa gcactcaaag acgtaccact ttcccaaaac tgtcactcag900agtctaaaga agaccatcag gttccttcac agcttcacaa tgtacaaatt gtatcagaag960ttatttttag aaatgatagg taaccaggtc caatcagtaa aaataagctg ctta 1014<210>54<211>338<212>PRT<213>智人(Homo sapiens)<400>54Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His Thr Ser Asp Glu1 5 10 15Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu Gln Tyr Val Lys Gln20 25 30Glu Cys Asn Arg Thr His Asn Arg Val Cys Glu Cys Lys Glu Gly Arg
35 40 45Tyr Leu Glu Ile Glu Phe Cys Leu Lys His Arg Ser Cys Pro Pro Gly50 55 60Phe Gly Val Val Gln Ala Gly Thr Pro Glu Arg Asn Thr Val Cys Lys65 70 75 80Arg Cys Pro Asp Gly Phe Phe Ser Asn Glu Thr Ser Ser Lys Ala Pro85 90 95Cys Arg Lys His Thr Asn Cys Ser Val Phe Gly Leu Leu Leu Thr Gln100 105 110Lys Gly Asn Ala Thr His Asp Asn Ile Cys Ser Gly Asn Ser Glu Ser115 120 125Thr Gln Lys Cys Gly Ile Asp Val Thr Leu Cys Glu Glu Ala Phe Phe130 135 140Arg Phe Ala Val Pro Thr Lys Phe Thr Pro Asn Trp Leu Ser Val Leu145 150 155 160Val Asp Asn Leu Pro Gly Thr Lys Val Asn Ala Glu Ser Val Glu Arg165 170 175Ile Lys Arg Gln His Ser Ser Gln Glu Gln Thr Phe Gln Leu Leu Lys180 185 190Leu Trp Lys His Gln Asn Lys Asp Gln Asp Ile Val Lys Lys Ile Ile195 200 205Gln Asp Ile Asp Leu Cys Glu Asn Ser Val Gln Arg His Ile Gly His210 215 220Ala Asn Leu Thr Phe Glu Gln Leu Arg Ser Leu Met Glu Ser Leu Pro225 230 235 240Gly Lys Lys Val Gly Ala Glu Asp Ile Glu Lys Thr Ile Lys Ala Cys245 250 255Lys Pro Ser Asp Gln Ile Leu Lys Leu Leu Ser Leu Trp Arg Ile Lys260 265 270Asn Gly Asp Gln Asp Thr Leu Lys Gly Leu Met His Ala Leu Lys His275 280 285Ser Lys Thr Tyr His Phe Pro Lys Thr Val Thr Gln Ser Leu Lys Lys290 295 300Thr Ile Arg Phe Leu His Ser Phe Thr Met Tyr Lys Leu Tyr Gln Lys305 310 315 320
Leu Phe Leu Glu Met Ile Gly Asn Gln Val Gln Ser Val Lys Ile Ser325 330 335Cys Leu<210>55<211>2312<212>DNA<213>智人(Homo sapiens)<400>55tccagtgacg gagccgcccg gccgacagcc ccgagacgac agcccggcgc gtcccggtcc 60ccacctccga ccaccgccag cgctccaggc cccgcgctcc ccgctcgccg ccaccgcgcc120ctccgctccg cccgcagtgc caaccatgac cgccgccagt atgggccccg tccgcgtcgc180cttcgtggtc ctcctcgccc tctgcagccg gccggccgtc ggccagaact gcagcgggcc240gtgccggtgc ccggacgagc cggcgccgcg ctgcccggcg ggcgtgagcc tcgtgctgga300cggctgcggc tgctgccgcg tctgcgccaa gcagctgggc gagctgtgca ccgagcgcga360cccctgcgac ccgcacaagg gcctcttctg tgacttcggc tccccggcca accgcaagat420cggcgtgtgc accgccaaag atggtgctcc ctgcatcttc ggtggtacgg tgtaccgcag480cggagagtcc ttccagagca gctgcaagta ccagtgcacg tgcctggacg gggcggtggg540ctgcatgccc ctgtgcagca tggacgttcg tctgcccagc cctgactgcc ccttcccgag600gagggtcaag ctgcccggga aatgctgcga ggagtgggtg tgtgacgagc ccaaggacca660aaccgtggtt gggcctgccc tcgcggctta ccgactggaa gacacgtttg gcccagaccc720aactatgatt agagccaact gcctggtcca gaccacagag tggagcgcct gttccaagac780ctgtgggatg ggcatctcca cccgggttac caatgacaac gcctcctgca ggctagagaa840gcagagccgc ctgtgcatgg tcaggccttg cgaagctgac ctggaagaga acattaagaa900gggcaaaaag tgcatccgta ctcccaaaat ctccaagcct atcaagtttg agctttctgg960ctgcaccagc atgaagacat accgagctaa attctgtgga gtatgtaccg acggccgatg 1020ctgcaccccc cacagaacca ccaccctgcc ggtggagttc aagtgccctg acggcgaggt 1080catgaagaag aacatgatgt tcatcaagac ctgtgcctgc cattacaact gtcccggaga 1140caatgacatc tttgaatcgc tgtactacag gaagatgtac ggagacatgg catgaagcca 1200gagagtgaga gacattaact cattagactg gaacttgaac tgattcacat ctcatttttc 1260cgtaaaaatg atttcagtag cacaagttat ttaaatctgt ttttctaact gggggaaaag 1320attcccaccc aattcaaaac attgtgccat gtcaaacaaa tagtctatct tccccagaca 1380ctggtttgaa gaatgttaag acttgacagt ggaactacat tagtacacag caccagaatg 1440tatattaagg tgtggcttta ggagcagtgg gagggtacca gcagaaaggt tagtatcatc 1500agatagctct tatacgagta atatgcctgc tatttgaagt gtaattgaga aggaaaattt 1560tagcgtgctc actgacctgc ctgtagcccc agtgacagct aggatgtgca ttctccagcc 1620atcaagagac tgagtcaagt tgttccttaa gtcagaacag cagactcagc tctgacattc 1680tgattcgaat gacactgttc aggaatcgga atcctgtcga ttagactgga cagcttgtgg 1740caagtgaatt tcctgtaaca agccagattt tttaaaattt atattgtaaa tattgtgtgt 1800gtgtgtgtgt gtgtatatat atatatatat gtacagttat ctaagttaat ttaaagttgt 1860ttgtgccttt ttatttttgt ttttaatgct ttgatatttc aatgttagcc tcaatttctg 1920aacaccatag gtagaatgta aagcttgtct gatcgttcaa agcatgaaat ggatacttat 1980atggaaattc tctcagatag aatgacagtc cgtcaaaaca gattgtttgc aaaggggagg 2040catcagtgtc cttggcaggc tgatttctag gtaggaaatg tggtagctca cgctcacttt 2100taatgaacaa atggccttta ttaaaaactg agtgactcta tatagctgat cagttttttc 2160acctggaagc atttgtttct actttgatat gactgttttt cggacagttt atttgttgag 2220agtgtgacca aaagttacat gtttgcacct ttctagttga aaataaagta tattttttct 2280aaaaaaaaaa aaaaacgaca gcaacggaat tc 2312
<210>56<211>349<212>PRT<213>智人(Homo sapiens)<400>56Met Thr Ala Ala Ser Met Gly Pro Val Arg Val Ala Phe Val Val Leu1 5 10 15Leu Ala Leu Cys Ser Arg Pro Ala Val Gly Gln Asn Cys Ser Gly Pro20 25 30Cys Arg Cys Pro Asp Glu Pro Ala Pro Arg Cys Pro Ala Gly Val Ser35 40 45Leu Val Leu Asp Gly Cys Gly Cys Cys Arg Val Cys Ala Lys Gln Leu50 55 60Gly Glu Leu Cys Thr Glu Arg Asp Pro Cys Asp Pro His Lys Gly Leu65 70 75 80Phe Cys Asp Phe Gly Ser Pro Ala Asn Arg Lys Ile Gly Val Cys Thr85 90 95Ala Lys Asp Gly Ala Pro Cys Ile Phe Gly Gly Thr Val Tyr Arg Ser100 105 110Gly Glu Ser Phe Gln Ser Ser Cys Lys Tyr Gln Cys Thr Cys Leu Asp115 120 125Gly Ala Val Gly Cys Met Pro Leu Cys Ser Met Asp Val Arg Leu Pro130 135 140Ser Pro Asp Cys Pro Phe Pro Arg Arg Val Lys Leu Pro Gly Lys Cys145 150 155 160Cys Glu Glu Trp Val Cys Asp Glu Pro Lys Asp Gln Thr Val Val Gly165 170 175Pro Ala Leu Ala Ala Tyr Arg Leu Glu Asp Thr Phe Gly Pro Asp Pro180 185 190Thr Met Ile Arg Ala Asn Cys Leu Val Gln Thr Thr Glu Trp Ser Ala195 200 205Cys Ser Lys Thr Cys Gly Met Gly Ile Ser Thr Arg Val Thr Asn Asp210 215 220Asn Ala Ser Cys Arg Leu Glu Lys Gln Ser Arg Leu Cys Met Val Arg225 230 235 240
Pro Cys Glu Ala Asp Leu Glu Glu Asn Ile Lys Lys Gly Lys Lys Cys245 250 255Ile Arg Thr Pro Lys Ile Ser Lys Pro Ile Lys Phe Glu Leu Ser Gly260 265 270Cys Thr Ser Met Lys Thr Tyr Arg Ala Lys Phe Cys Gly Val Cys Thr275 280 285Asp Gly Arg Cys Cys Thr Pro His Arg Thr Thr Thr Leu Pro Val Glu290 295 300Phe Lys Cys Pro Asp Gly Glu Val Met Lys Lys Asn Met Met Phe Ile305 310 315 320Lys Thr Cys Ala Cys His Tyr Asn Cys Pro Gly Asp Asn Asp Ile Phe325 330 335Glu Ser Leu Tyr Tyr Arg Lys Met Tyr Gly Asp Met Ala340 345<210>57<211>1069<212>DNA<213>智人(Homo sapiens)<400>57cagaactgca gcgggccgtg ccggtgcccg gacgagccgg cgccgcgctg cccggcgggc60gtgagcctcg tgctggacgg ctgcggctgc tgccgcgtct gcgccaagca gctgggcgag 120ctgtgcaccg agcgcgaccc ctgcgacccg cacaagggcc tcttctgtga cttcggctcc 180ccggccaacc gcaagatcgg cgtgtgcacc gccaaagatg gtgctccctg catcttcggt 240ggtacggtgt accgcagcgg agagtccttc cagagcagct gcaagtacca gtgcacgtgc 300ctggacgggg cggtgggctg catgcccctg tgcagcatgg acgttcgtct gcccagccct 360gactgcccct tcccgaggag ggtcaagctg cccgggaaat gctgcgagga gtgggtgtgt 420gacgagccca aggaccaaac cgtggttggg cctgccctcg cggcttaccg actggaagac 480acgtttggcc cagacccaac tatgattaga gccaactgcc tggtccagac cacagagtgg 540agcgcctgtt ccaagacctg tgggatgggc atctccaccc gggttaccaa tgacaacgcc 600tcctgcaggc tagagaagca gagccgcctg tgcatggtca ggccttgcga agctgacctg 660gaagagaaca ttaagaaggg caaaaagtgc atccgtactc ccaaaatctc caagcctatc 720aagtttgagc tttctggctg caccagcatg aagacatacc gagctaaatt ctgtggagta 780tgtaccgacg gccgatgctg caccccccac agaaccacca ccctgccggt ggagttcaag 840tgccctgacg gcgaggtcat gaagaagaac atgatgttca tcaagacctg tgcctgccat 900tacaactgtc ccggagacaa tgacatcttt gaatcgctgt actacaggaa gatgtacgga 960gacatggcat gaagccagag agtgagagac attaactcat tagactggaa cttgaactga 1020ttcacatctc atttttccgt aaaaatgatt tcagtagcac aagttattt 1069<210>58<211>323<212>PRT<213>智人(Homo sapiens)<400>58
Gln Asn Cys Ser Gly Pro Cys Arg Cys Pro Asp Glu Pro Ala Pro Arg1 5 10 15Cys Pro Ala Gly Val Ser Leu Val Leu Asp Gly Cys Gly Cys Cys Arg20 25 30Val Cys Ala Lys Gln Leu Gly Glu Leu Cys Thr Glu Arg Asp Pro Cys35 40 45Asp Pro His Lys Gly Leu Phe Cys Asp Phe Gly Ser Pro Ala Asn Arg50 55 60Lys Ile Gly Val Cys Thr Ala Lys Asp Gly Ala Pro Cys Ile Phe Gly65 70 75 80Gly Thr Val Tyr Arg Ser Gly Glu Ser Phe Gln Ser Ser Cys Lys Tyr85 90 95Gln Cys Thr Cys Leu Asp Gly Ala Val Gly Cys Met Pro Leu Cys Ser100 105 110Met Asp Val Arg Leu Pro Ser Pro Asp Cys Pro Phe Pro Arg Arg Val115 120 125Lys Leu Pro Gly Lys Cys Cys Glu Glu Trp Val Cys Asp Glu Pro Lys130 135 140Asp Gln Thr Val Val Gly Pro Ala Leu Ala Ala Tyr Arg Leu Glu Asp145 150 155 160Thr Phe Gly Pro Asp Pro Thr Met Ile Arg Ala Asn Cys Leu Val Gln165 170 175Thr Thr Glu Trp Ser Ala Cys Ser Lys Thr Cys Gly Met Gly Ile Ser180 185 190Thr Arg Val Thr Asn Asp Asn Ala Ser Cys Arg Leu Glu Lys Gln Ser195 200 205Arg Leu Cys Met Val Arg Pro Cys Glu Ala Asp Leu Glu Glu Asn Ile210 215 220Lys Lys Gly Lys Lys Cys Ile Arg Thr Pro Lys Ile Ser Lys Pro Ile225 230 235 240Lys Phe Glu Leu Ser Gly Cys Thr Ser Met Lys Thr Tyr Arg Ala Lys245 250 255Phe Cys Gly Val Cys Thr Asp Gly Arg Cys Cys Thr Pro His Arg Thr260 265 270Thr Thr Leu Pro Val Glu Phe Lys Cys Pro Asp Gly Glu Val Met Lys
275 280 285Lys Asn Met Met Phe Ile Lys Thr Cys Ala Cys His Tyr Asn Cys Pro290 295 300Gly Asp Asn Asp Ile Phe Glu Ser Leu Tyr Tyr Arg Lys Met Tyr Gly305 310 315 320Asp Met Ala<210>59<211>1985<212>DNA<213>智人(Homo sapiens)<400>59gagcgaaaga cgcccgcccg ccgcccagcc ctcgcctccc tgcccaccgg gcccaccgcg 60ccgccacccc gaccccgctg cgcacggcct gtccgctgca caccagcttg ttggcgtctt120cgtcgccgcg ctcgccccgg gctactcctg cgcgccacaa tgagctcccg catcgccagg180gcgctcgcct tagtcgtcac ccttctccac ttgaccaggc tggcgctctc cacctgcccc240gctgcctgcc actgccccct ggaggcgccc aagtgcgcgc cgggagtcgg gctggtccgg300gacggctgcg gctgctgtaa ggtctgcgcc aagcagctca acgaggactg cagcaaaacg360cagccctgcg accacaccaa ggggctggaa tgcaacttcg gcgccagctc caccgctctg420aaggggatct gcagagctca gtcagagggc agaccctgtg aatataactc cagaatctac480caaaacgggg aaagtttcca gcccaactgt aaacatcagt gcacatgtat tgatggcgcc540gtgggctgca ttcctctgtg tccccaagaa ctatctctcc ccaacttggg ctgtcccaac600cctcggctgg tcaaagttac cgggcagtgc tgcgaggagt gggtctgtga cgaggatagt660atcaaggacc ccatggagga ccaggacggc ctccttggca aggagctggg attcgatgcc720tccgaggtgg agttgacgag aaacaatgaa ttgattgcag ttggaaaagg cagctcactg780aagcggctcc ctgtttttgg aatggagcct cgcatcctat acaacccttt acaaggccag840aaatgtattg ttcaaacaac ttcatggtcc cagtgctcaa agacctgtgg aactggtatc900tccacacgag ttaccaatga caaccctgag tgccgccttg tgaaagaaac ccggatttgt960gaggtgcggc cttgtggaca gccagtgtac agcagcctga aaaagggcaa gaaatgcagc 1020aagaccaaga aatcccccga accagtcagg tttacttacg ctggatgttt gagtgtgaag 1080aaataccggc ccaagtactg cggttcctgc gtggacggcc gatgctgcac gccccagctg 1140accaggactg tgaagatgcg gttccgctgc gaagatgggg agacattttc caagaacgtc 1200atgatgatcc agtcctgcaa atgcaactac aactgcccgc atgccaatga agcagcgttt 1260cccttctaca ggctgttcaa tgacattcac aaatttaggg actaaatgct acctgggttt 1320ccagggcaca cctagacaaa caagggagaa gagtgtcaga atcagaatca tggagaaaat 1380gggcgggggt ggtgtgggtg atgggactca ttgtagaaag gaagccttgc tcattcttga 1440ggagcattaa ggtatttcga aactgccaag ggtgctggtg cggatggaca ctaatgcagc 1500cacgattgga gaatactttg cttcatagta ttggagcaca tgttactgct tcattttgga 1560gcttgtggag ttgatgactt tctgttttct gtttgtaaat tatttgctaa gcatattttc 1620tctaggcttt tttccttttg gggttctaca gtcgtaaaag agataataag attagttgga 1680cagtttaaag cttttattcg tcctttgaca aaagtaaatg ggagggcatt ccatcccttc 1740ctgaaggggg acactccatg agtgtctgtg agaggcagct atctgcactc taaactgcaa 1800acagaaatca ggtgttttaa gactgaatgt tttatttatc aaaatgtagc ttttggggag 1860ggaggggaaa tgtaatactg gaataatttg taaatgattt taattttata ttcagtgaaa 1920agattttatt tatggaatta accatttaat aaagaaatat ttacctaata aaaaaaaaaa 1980aaaaa 1985
<210>60<211>381<212>PRT<213>智人(Homo sapiens)<400>60Met Ser Ser Arg Ile Ala Arg Ala Leu Ala Leu Val Val Thr Leu Leu1 5 10 15His Leu Thr Arg Leu Ala Leu Ser Thr Cys Pro Ala Ala Cys His Cys20 25 30Pro Leu Glu Ala Pro Lys Cys Ala Pro Gly Val Gly Leu Val Arg Asp35 40 45Gly Cys Gly Cys Cys Lys Val Cys Ala Lys Gln Leu Asn Glu Asp Cys50 55 60Ser Lys Thr Gln Pro Cys Asp His Thr Lys Gly Leu Glu Cys Asn Phe65 70 75 80Gly Ala Ser Ser Thr Ala Leu Lys Gly Ile Cys Arg Ala Gln Ser Glu85 90 95Gly Arg Pro Cys Glu Tyr Asn Ser Arg Ile Tyr Gln Asn Gly Glu Ser100 105 110Phe Gln Pro Asn Cys Lys His Gln Cys Thr Cys Ile Asp Gly Ala Val115 120 125Gly Cys Ile Pro Leu Cys Pro Gln Glu Leu Ser Leu Pro Asn Leu Gly130 135 140Cys Pro Asn Pro Arg Leu Val Lys Val Thr Gly Gln Cys Cys Glu Glu145 150 155 160Trp Val Cys Asp Glu Asp Ser Ile Lys Asp Pro Met Glu Asp Gln Asp165 170 175Gly Leu Leu Gly Lys Glu Leu Gly Phe Asp Ala Ser Glu Val Glu Leu180 185 190Thr Arg Asn Asn Glu Leu Ile Ala Val Gly Lys Gly Ser Ser Leu Lys195 200 205Arg Leu Pro Val Phe Gly Met Glu Pro Arg Ile Leu Tyr Asn Pro Leu210 215 220Gln Gly Gln Lys Cys Ile Val Gln Thr Thr Ser Trp Ser Gln Cys Ser225 230 235 240Lys Thr Cys Gly Thr Gly Ile Ser Thr Arg Val Thr Asn Asp Asn Pro
245 250 255Glu Cys Arg Leu Val Lys Glu Thr Arg Ile Cys Glu Val Arg Pro Cys260 265 270Gly Gln Pro Val Tyr Ser Ser Leu Lys Lys Gly Lys Lys Cys Ser Lys275 280 285Thr Lys Lys Ser Pro Glu Pro Val Arg Phe Thr Tyr Ala Gly Cys Leu290 295 300Ser Val Lys Lys Tyr Arg Pro Lys Tyr Cys Gly Ser Cys Val Asp Gly305 310 315 320Arg Cys Cys Thr Pro Gln Leu Thr Arg Thr Val Lys Met Arg Phe Arg325 330 335Cys Glu Asp Gly Glu Thr Phe Ser Lys Asn Val Met Met Ile Gln Ser340 345 350Cys Lys Cys Asn Tyr Asn Cys Pro His Ala Asn Glu Ala Ala Phe Pro355 360 365Phe Tyr Arg Leu Phe Asn Asp Ile His Lys Phe Arg Asp370 375 380<210>61<211>2830<212>DNA<213>智人(Homo sapiens)<400>61cccacgcgtc cgctgggccc agctcccccg agaggtggtc ggatcctctg ggctgctcgg60tcgatgcctg tgccactgac gtccaggcat gaggtggttc ctgccctgga cgctggcagc 120agtgacagca gcagccgcca gcaccgtcct ggccacggcc ctctctccag cccctacgac 180catggacttt actccagctc cactggagga cacctcctca cgcccccaat tctgcaagtg 240gccatgtgag tgcccgccat ccccaccccg ctgcccgctg ggggtcagcc tcatcacaga 300tggctgtgag tgctgtaaga tgtgcgctca gcagcttggg gacaactgca cggaggctgc 360catctgtgac ccccaccggg gcctctactg tgactacagc ggggaccgcc cgaggtacgc 420aataggagtg tgtgcacagg tggtcggtgt gggctgcgtc ctggatgggg tgcgctacaa 480caacggccag tccttccagc ctaactgcaa gtacaactgc acgtgcatcg acggcgcggt 540gggctgcaca ccactgtgcc tccgagtgcg ccccccgcgt ctctggtgcc cccacccgcg 600gcgcgtgagc atacctggcc actgctgtga gcagtgggta tgtgaggacg acgccaagag 660gccacgcaag accgcacccc gtgacacagg agccttcgat gctgtgggtg aggtggaggc 720atggcacagg aactgcatag cctacacaag cccctggagc ccttgctcca ccagctgcgg 780cctgggggtc tccactcgga tctccaatgt taacgcccag tgctggcctg agcaagagag 840ccgcctctgc aacttgcggc catgcgatgt ggacatccat acactcatta aggcagggaa 900gaagtgtctg gctgtgtacc agccagaggc atccatgaac ttcacacttg cgggctgcat 960cagcacacgc tcctatcaac ccaagtactg tggagtttgc atggacaata ggtgctgcat 1020cccctacaag tctaagacta tcgacgtgtc cttccagtgt cctgatgggc ttggcttctc 1080ccgccaggtc ctatggatta atgcctgctt ctgtaacctg agctgtagga atcccaatga 1140catctttgct gacttggaat cctaccctga cttctcagaa attgccaact aggcaggcac 1200
aaatcttggg tcttggggac taacccaatg cctgtgaagc agtcagccct tatggccaat1260aacttttcac caatgagcct tagttaccct gatctggacc cttggcctcc atttctgtct1320ctaaccattc aaatgacgcc tgatggtgct gctcaggccc atgctatgag ttttctcctt1380gatatcattc agcatctact ctaaagaaaa atgcctgtct ctagctgttc tggactacac1440ccaagcctga tccagccttt ccaagtcact agaagtcctg ctggatcttg cctaaatccc1500aagaaatgga atcaggtaga cttttaatat cactaatttc ttctttagat gccaaaccac1560aagactcttt gggtccattc agatgaatag atggaatttg gaacaataga ataatctatt1620atttggagcc tgccaagagg tactgtaatg ggtaattctg acgtcagcgc accaaaacta1680tcctgattcc aaatatgtat gcacctcaag gtcatcaaac atttgccaag tgagttgaat1740agttgcttaa ttttgatttt taatggaaag ttgtatccat taacctgggc attgttgagg1800ttaagtttct cttcacccct acactgtgaa gggtacagat taggtttgtc ccagtcagaa1860ataaaatttg ataaacattc ctgttgatgg gaaaagcccc cagttaatac tccagagaca1920gggaaaggtc agcccatttc agaaggacca attgactctc acactgaatc agctgctgac1980tggcagggct ttgggcagtt ggccaggctc ttccttgaat cttctccctt gtcctgcttg2040ggttcatagg aattggtaag gcctctggac tggcctgtct ggcccctgag agtggtgccc2100tggaacactc ctctactctt acagagcctt gagagaccca gctgcagacc atgccagacc2160cactgaaatg accaagacag gttcaggtag gggtgtgggt caaaccaaga agtgggtgcc2220cttggtagca gcctggggtg acctctagag ctggaggctg tgggactcca ggggcccccg2280tgttcaggac acatctattg cagagactca tttcacagcc tttcgttctg ctgaccaaat2340ggccagtttt ctggtaggaa gatggaggtt taccagttgt ttagaaacag aaatagactt2400aataaaggtt taaagctgaa gaggttgaag ctaaaaggaa aaggttgttg ttaatgaata2460tcaggctatt atttattgta ttaggaaaat ataatattta ctgttagaat tcttttattt2520agggcctttt ctgtgccaga cattgctctc agtgctttgc atgtattagc tcactgaatc2580ttcacgacaa tgttgagaag ttcccattat tatttctgtt cttacaaatg tgaaacggaa2640gctcatagag gtgagaaaac tcaaccagag tcacccagtt ggtgactggg aaagttagga2700ttcagatcga aattggactg tctttataac ccatattttc cccctgtttt tagagcttcc2760aaatgtgtca gaataggaaa acattgcaat aaatggcttg attttttaaa aaaaaaaaaa2820aaaaaaaaaa 2830<210>62<211>367<212>PRT<213>智人(Homo sapiens)<400>62Met Arg Trp Phe Leu Pro Trp Thr Leu Ala Ala Val Thr Ala Ala Ala1 5 10 15Ala Ser Thr Val Leu Ala Thr Ala Leu Ser Pro Ala Pro Thr Thr Met20 25 30Asp Phe Thr Pro Ala Pro Leu Glu Asp Thr Ser Ser Arg Pro Gln Phe35 40 45Cys Lys Trp Pro Cys Glu Cys Pro Pro Ser Pro Pro Arg Cys Pro Leu50 55 60Gly Val Ser Leu Ile Thr Asp Gly Cys Glu Cys Cys Lys Met Cys Ala65 70 75 80Gln Gln Leu Gly Asp Asn Cys Thr Glu Ala Ala Ile Cys Asp Pro His85 90 95
Arg Gly Leu Tyr Cys Asp Tyr Ser Gly Asp Arg Pro Arg Tyr Ala Ile100 105 110Gly Val Cys Ala Gln Val Val Gly Val Gly Cys Val Leu Asp Gly Val115 120 125Arg Tyr Asn Asn Gly Gln Ser Phe Gln Pro Asn Cys Lys Tyr Asn Cys130 135 140Thr Cys Ile Asp Gly Ala Val Gly Cys Thr Pro Leu Cys Leu Arg Val145 150 155 160Arg Pro Pro Arg Leu Trp Cys Pro His Pro Arg Arg Val Ser Ile Pro165 170 175Gly His Cys Cys Glu Gln Trp Val Cys Glu Asp Asp Ala Lys Arg Pro180 185 190Arg Lys Thr Ala Pro Arg Asp Thr Gly Ala Phe Asp Ala Val Gly Glu195 200 205Val Glu Ala Trp His Arg Asn Cys Ile Ala Tyr Thr Ser Pro Trp Ser210 215 220Pro Cys Ser Thr Ser Cys Gly Leu Gly Val Ser Thr Arg Ile Ser Asn225 230 235 240Val Asn Ala Gln Cys Trp Pro Glu Gln Glu Ser Arg Leu Cys Asn Leu245 250 255Arg Pro Cys Asp Val Asp Ile His Thr Leu Ile Lys Ala Gly Lys Lys260 265 270Cys Leu Ala Val Tyr Gln Pro Glu Ala Ser Met Asn Phe Thr Leu Ala275 280 285Gly Cys Ile Ser Thr Arg Ser Tyr Gln Pro Lys Tyr Cys Gly Val Cys290 295 300Met Asp Asn Arg Cys Cys Ile Pro Tyr Lys Ser Lys Thr Ile Asp Val305 310 315 320Ser Phe Gln Cys Pro Asp Gly Leu Gly Phe Ser Arg Gln Val Leu Trp325 330 335Ile Asn Ala Cys Phe Cys Asn Leu Ser Cys Arg Asn Pro Asn Asp Ile340 345 350Phe Ala Asp Leu Glu Ser Tyr Pro Asp Phe Ser Glu Ile Ala Asn355 360 365
<210>63<211>1723<212>DNA<213>智人(Homo sapiens)<400>63tcgcggaggc ttggggcagc cgggtagctc ggaggtcgtg gcgctggggg ctagcaccag60cgctctgtcg ggaggcgcag cggttaggtg gaccggtcag cggactcacc ggccagggcg 120ctcggtgctg gaatttgata ttcattgatc cgggttttat ccctcttctt ttttcttaaa 180catttttttt taaaactgta ttgtttctcg ttttaattta tttttgcttg ccattcccca 240cttgaatcgg gccgacggct tggggagatt gctctacttc cccaaatcac tgtggatttt 300ggaaaccagc agaaagagga aagaggtagc aagagctcca gagagaagtc gaggaagaga 360gagacggggt cagagagagc gcgcgggcgt gcgagcagcg aaagcgacag gggcaaagtg 420agtgacctgc ttttgggggt gaccgccgga gcgcggcgtg agccctcccc cttgggatcc 480cgcagctgac cagtcgcgct gacggacaga cagacagaca ccgcccccag ccccagctac 540cacctcctcc ccggccggcg gcggacagtg gacgcggcgg cgagccgcgg gcaggggccg 600gagcccgcgc ccggaggcgg ggtggagggg gtcggggctc gcggcgtcgc actgaaactt 660ttcgtccaac ttctgggctg ttctcgcttc ggaggagccg tggtccgcgc gggggaagcc 720gagccgagcg gagccgcgag aagtgctagc tcgggccggg aggagccgca gccggaggag 780ggggaggagg aagaagagaa ggaagaggag agggggccgc agtggcgact cggcgctcgg 840aagccgggct catggacggg tgaggcggcg gtgtgcgcag acagtgctcc agccgcgcgc 900gctccccagg ccctggcccg ggcctcgggc cggggaggaa gagtagctcg ccgaggcgcc 960gaggagagcg ggccgcccca cagcccgagc cggagaggga gcgcgagccg cgccggcccc 1020ggtcgggcct ccgaaaccat gaactttctg ctgtcttggg tgcattggag ccttgccttg 1080ctgctctacc tccaccatgc caagtggtcc caggctgcac ccatggcaga aggaggaggg 1140cagaatcatc acgaagtggt gaagttcatg gatgtctatc agcgcagcta ctgccatcca 1200atcgagaccc tggtggacat cttccaggag taccctgatg agatcgagta catcttcaag 1260ccatcctgtg tgcccctgat gcgatgcggg ggctgctgca atgacgaggg cctggagtgt 1320gtgcccactg aggagtccaa catcaccatg cagattatgc ggatcaaacc tcaccaaggc 1380cagcacatag gagagatgag cttcctacag cacaacaaat gtgaatgcag accaaagaaa 1440gatagagcaa gacaagaaaa aaaatcagtt cgaggaaagg gaaaggggca aaaacgaaag 1500cgcaagaaat cccggtataa gtcctggagc gttccctgtg ggccttgctc agagcggaga 1560aagcatttgt ttgtacaaga tccgcagacg tgtaaatgtt cctgcaaaaa cacagactcg 1620cgttgcaagg cgaggcagct tgagttaaac gaacgtactt gcagatgtga caagccgagg 1680cggtgagccg ggcaggagga aggagcctcc ctcagggttt cgg1723<210>64<211>215<212>PRT<213>智人(Homo sapiens)<400>64Met Asn Phe Leu Leu Ser Trp Val His Trp Ser Leu Ala Leu Leu Leu1 5 10 15Tyr Leu His His Ala Lys Trp Ser Gln Ala Ala Pro Met Ala Glu Gly20 25 30Gly Gly Gln Asn His His Glu Val Val Lys Phe Met Asp Val Tyr Gln35 40 45Arg Ser Tyr Cys His Pro Ile Glu Thr Leu Val Asp Ile Phe Gln Glu
50 55 60Tyr Pro Asp Glu Ile Glu Tyr Ile Phe Lys Pro Ser Cys Val Pro Leu65 70 75 80Met Arg Cys Gly Gly Cys Cys Asn Asp Glu Gly Leu Glu Cys Val Pro85 90 95Thr Glu Glu Ser Asn Ile Thr Met Gln Ile Met Arg Ile Lys Pro His100 105 110Gln Gly Gln His Ile Gly Glu Met Ser Phe Leu Gln His Asn Lys Cys115 120 125Glu Cys Arg Pro Lys Lys Asp Arg Ala Arg Gln Glu Lys Lys Ser Val130 135 140Arg Gly Lys Gly Lys Gly Gln Lys Arg Lys Arg Lys Lys Ser Arg Tyr145 150 155 160Lys Ser Trp Ser Val Pro Cys Gly Pro Cys Ser Glu Arg Arg Lys His165 170 175Leu Phe Val Gln Asp Pro Gln Thr Cys Lys Cys Ser Cys Lys Asn Thr180 185 190Asp Ser Arg Cys Lys Ala Arg Gln Leu Glu Leu Asn Glu Arg Thr Cys195 200 205Arg Cys Asp Lys Pro Arg Arg210 215<210>65<211>1172<212>DNA<213>智人(Homo sapiens)<400>65gcgatgcggg cgcccccggc gggcggcccc ggcgggcacc atgagccctc tgctccgccg60cctgctgctc gccgcactcc tgcagctggc ccccgcccag gcccctgtct cccagcctga 120tgcccctggc caccagagga aagtggtgtc atggatagat gtgtatactc gcgctacctg 180ccagccccgg gaggtggtgg tgcccttgac tgtggagctc atgggcaccg tggccaaaca 240gctggtgccc agctgcgtga ctgtgcagcg ctgtggtggc tgctgccctg acgatggcct 300ggagtgtgtg cccactgggc agcaccaagt ccggatgcag atcctcatga tccggtaccc 360gagcagtcag ctgggggaga tgtccctgga agaacacagc cagtgtgaat gcagacctaa 420aaaaaaggac agtgctgtga agccagacag ggctgccact ccccaccacc gtccccagcc 480ccgttctgtt ccgggctggg actctgcccc cggagcaccc tccccagctg acatcaccca 540tcccactcca gccccaggcc cctctgccca cgctgcaccc agcaccacca gcgccctgac 600ccccggacct gccgctgccg ctgccgacgc cgcagcttcc tccgttgcca agggcggggc 660ttagagctca acccagacac ctgcaggtgc cggaagctgc gaaggtgaca catggctttt 720cagactcagc agggtgactt gcctcagagg ctatatccca gtgggggaac aaagaggagc 780ctggtaaaaa acagccaagc ccccaagacc tcagcccagg cagaagctgc tctaggacct 840
gggcctctca gagggctctt ctgccatccc ttgtctccct gaggccatca tcaaacagga 900cagagttgga agaggagact gggaggcagc aagaggggtc acataccagc tcaggggaga 960atggagtact gtctcagttt ctaaccactc tgtgcaagta agcatcttac aactggctct 1020tcctcccctc actaagaaga cccaaacctc tgcataatgg gatttgggct ttggtacaag 1080aactgtgacc cccaaccctg ataaaagaga tggaaggaaa aaaaaaaaaa aaaaaaaaaa 1140aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aa1172<210>66<211>207<212>PRT<213>智人(Homo sapiens)<400>66Met Ser Pro Leu Leu Arg Arg Leu Leu Leu Ala Ala Leu Leu Gln Leu1 5 10 15Ala Pro Ala Gln Ala Pro Val Ser Gln Pro Asp Ala Pro Gly His Gln20 25 30Arg Lys Val Val Ser Trp Ile Asp Val Tyr Thr Arg Ala Thr Cys Gln35 40 45Pro Arg Glu Val Val Val Pro Leu Thr Val Glu Leu Met Gly Thr Val50 55 60Ala Lys Gln Leu Val Pro Ser Cys Val Thr Val Gln Arg Cys Gly Gly65 70 75 80Cys Cys Pro Asp Asp Gly Leu Glu Cys Val Pro Thr Gly Gln His Gln85 90 95Val Arg Met Gln Ile Leu Met Ile Arg Tyr Pro Ser Ser Gln Leu Gly100 105 110Glu Met Ser Leu Glu Glu His Ser Gln Cys Glu Cys Arg Pro Lys Lys115 120 125Lys Asp Ser Ala Val Lys Pro Asp Arg Ala Ala Thr Pro His His Arg130 135 140Pro Gln Pro Arg Ser Val Pro Gly Trp Asp Ser Ala Pro Gly Ala Pro145 150 155 160Ser Pro Ala Asp Ile Thr His Pro Thr Pro Ala Pro Gly Pro Ser Ala165 170 175His Ala Ala Pro Ser Thr Thr Ser Ala Leu Thr Pro Gly Pro Ala Ala180 185 190Ala Ala Ala Asp Ala Ala Ala Ser Ser Val Ala Lys Gly Gly Ala195 200 205
<210>67<211>2076<212>DNA<213>智人(Homo sapiens)<400>67cggggaaggg gagggaggag ggggacgagg gctctggcgg gtttggaggg gctgaacatc 60gcggggtgtt ctggtgtccc ccgccccgcc tctccaaaaa gctacaccga cgcggaccgc 120ggcggcgtcc tccctcgccc tcgcttcacc tcgcgggctc cgaatgcggg gagctcggat 180gtccggtttc ctgtgaggct tttacctgac acccgccgcc tttccccggc actggctggg 240agggcgccct gcaaagttgg gaacgcggag ccccggaccc gctcccgccg cctccggctc 300gcccaggggg ggtcgccggg aggagcccgg gggagaggga ccaggagggg cccgcggcct 360cgcaggggcg cccgcgcccc cacccctgcc cccgccagcg gaccggtccc ccacccccgg 420tccttccacc atgcacttgc tgggcttctt ctctgtggcg tgttctctgc tcgccgctgc 480gctgctcccg ggtcctcgcg aggcgcccgc cgccgccgcc gccttcgagt ccggactcga 540cctctcggac gcggagcccg acgcgggcga ggccacggct tatgcaagca aagatctgga 600ggagcagtta cggtctgtgt ccagtgtaga tgaactcatg actgtactct acccagaata 660ttggaaaatg tacaagtgtc agctaaggaa aggaggctgg caacataaca gagaacaggc 720caacctcaac tcaaggacag aagagactat aaaatttgct gcagcacatt ataatacaga 780gatcttgaaa agtattgata atgagtggag aaagactcaa tgcatgccac gggaggtgtg 840tatagatgtg gggaaggagt ttggagtcgc gacaaacacc ttctttaaac ctccatgtgt 900gtccgtctac agatgtgggg gttgctgcaa tagtgagggg ctgcagtgca tgaacaccag 960cacgagctac ctcagcaaga cgttatttga aattacagtg cctctctctc aaggccccaa1020accagtaaca atcagttttg ccaatcacac ttcctgccga tgcatgtcta aactggatgt1080ttacagacaa gttcattcca ttattagacg ttccctgcca gcaacactac cacagtgtca1140ggcagcgaac aagacctgcc ccaccaatta catgtggaat aatcacatct gcagatgcct1200ggctcaggaa gattttatgt tttcctcgga tgctggagat gactcaacag atggattcca1260tgacatctgt ggaccaaaca aggagctgga tgaagagacc tgtcagtgtg tctgcagagc1320ggggcttcgg cctgccagct gtggacccca caaagaacta gacagaaact catgccagtg1380tgtctgtaaa aacaaactct tccccagcca atgtggggcc aaccgagaat ttgatgaaaa1440cacatgccag tgtgtatgta aaagaacctg ccccagaaat caacccctaa atcctggaaa1500atgtgcctgt gaatgtacag aaagtccaca gaaatgcttg ttaaaaggaa agaagttcca1560ccaccaaaca tgcagctgtt acagacggcc atgtacgaac cgccagaagg cttgtgagcc1620aggattttca tatagtgaag aagtgtgtcg ttgtgtccct tcatattgga aaagaccaca1680aatgagctaa gattgtactg ttttccagtt catcgatttt ctattatgga aaactgtgtt1740gccacagtag aactgtctgt gaacagagag acccttgtgg gtccatgcta acaaagacaa1800aagtctgtct ttcctgaacc atgtggataa ctttacagaa atggactgga gctcatctgc1860aaaaggcctc ttgtaaagac tggttttctg ccaatgacca aacagccaag attttcctct1920tgtgatttct ttaaaagaat gactatataa tttatttcca ctaaaaatat tgtttctgca1980ttcattttta tagcaacaac aattggtaaa actcactgtg atcaatattt ttatatcatg2040caaaatatgt ttaaaataaa atgaaaattg tattat 2076<210>68<211>419<212>PRT<213>智人(Homo sapiens)<400>68Met His Leu Leu Gly Phe Phe Ser Val Ala Cys Ser Leu Leu Ala Ala1 5 10 15Ala Leu Leu Pro Gly Pro Arg Glu Ala Pro Ala Ala Ala Ala Ala Phe
20 25 30Glu Ser Gly Leu Asp Leu Ser Asp Ala Glu Pro Asp Ala Gly Glu Ala35 40 45Thr Ala Tyr Ala Ser Lys Asp Leu Glu Glu Gln Leu Arg Ser Val Ser50 55 60Ser Val Asp Glu Leu Met Thr Val Leu Tyr Pro Glu Tyr Trp Lys Met65 70 75 80Tyr Lys Cys Gln Leu Arg Lys Gly Gly Trp Gln His Asn Arg Glu Gln85 90 95Ala Asn Leu Asn Ser Arg Thr Glu Glu Thr Ile Lys Phe Ala Ala Ala100 105 110His Tyr Asn Thr Glu Ile Leu Lys Ser Ile Asp Asn Glu Trp Arg Lys115 120 125Thr Gln Cys Met Pro Arg Glu Val Cys Ile Asp Val Gly Lys Glu Phe130 135 140Gly Val Ala Thr Asn Thr Phe Phe Lys Pro Pro Cys Val Ser Val Tyr145 150 155 160Arg Cys Gly Gly Cys Cys Asn Ser Glu Gly Leu Gln Cys Met Asn Thr165 170 175Ser Thr Ser Tyr Leu Ser Lys Thr Leu Phe Glu Ile Thr Val Pro Leu180 185 190Ser Gln Gly Pro Lys Pro Val Thr Ile Ser Phe Ala Asn His Thr Ser195 200 205Cys Arg Cys Met Ser Lys Leu Asp Val Tyr Arg Gln Val His Ser Ile210 215 220Ile Arg Arg Ser Leu Pro Ala Thr Leu Pro Gln Cys Gln Ala Ala Asn225 230 235 240Lys Thr Cys Pro Thr Asn Tyr Met Trp Asn Asn His Ile Cys Arg Cys245 250 255Leu Ala Gln Glu Asp Phe Met Phe Ser Ser Asp Ala Gly Asp Asp Ser260 265 270Thr Asp Gly Phe His Asp Ile Cys Gly Pro Asn Lys Glu Leu Asp Glu275 280 285Glu Thr Cys Gln Cys Val Cys Arg Ala Gly Leu Arg Pro Ala Ser Cys290 295 300
Gly Pro His Lys Glu Leu Asp Arg Asn Ser Cys Gln Cys Val Cys Lys305 310 315 320Asn Lys Leu Phe Pro Ser Gln Cys Gly Ala Asn Arg Glu Phe Asp Glu325 330 335Asn Thr Cys Gln Cys Val Cys Lys Arg Thr Cys Pro Arg Asn Gln Pro340 345 350Leu Asn Pro Gly Lys Cys Ala Cys Glu Cys Thr Glu Ser Pro Gln Lys355 360 365Cys Leu Leu Lys Gly Lys Lys Phe His His Gln Thr Cys Ser Cys Tyr370 375 380Arg Arg Pro Cys Thr Asn Arg Gln Lys Ala Cys Glu Pro Gly Phe Ser385 390 395 400Tyr Ser Glu Glu Val Cys Arg Cys Val Pro Ser Tyr Trp Lys Arg Pro405 410 415Gln Met Ser<210>69<211>2029<212>DNA<213>智人(Homo sapiens)<400>69gttgggttcc agctttctgt agctgtaagc attggtggcc acaccacctc cttacaaagc 60aactagaacc tgcggcatac attggagaga tttttttaat tttctggaca tgaagtaaat120ttagagtgct ttctaatttc aggtagaaga catgtccacc ttctgattat ttttggagaa180cattttgatt tttttcatct ctctctcccc acccctaaga ttgtgcaaaa aaagcgtacc240ttgcctaatt gaaataattt cattggattt tgatcagaac tgattatttg gttttctgtg300tgaagttttg aggtttcaaa ctttccttct ggagaatgcc ttttgaaaca attttctcta360gctgcctgat gtcaactgct tagtaatcag tggatattga aatattcaaa atgtacagag420agtgggtagt ggtgaatgtt ttcatgatgt tgtacgtcca gctggtgcag ggctccagta480atgaacatgg accagtgaag cgatcatctc agtccacatt ggaacgatct gaacagcaga540tcagggctgc ttctagtttg gaggaactac ttcgaattac tcactctgag gactggaagc600tgtggagatg caggctgagg ctcaaaagtt ttaccagtat ggactctcgc tcagcatccc660atcggtccac taggtttgcg gcaactttct atgacattga aacactaaaa gttatagatg720aagaatggca aagaactcag tgcagcccta gagaaacgtg cgtggaggtg gccagtgagc780tggggaagag taccaacaca ttcttcaagc ccccttgtgt gaacgtgttc cgatgtggtg840gctgttgcaa tgaagagagc cttatctgta tgaacaccag cacctcgtac atttccaaac900agctctttga gatatcagtg cctttgacat cagtacctga attagtgcct gttaaagttg960ccaatcatac aggttgtaag tgcttgccaa cagccccccg ccatccatac tcaattatca 1020gaagatccat ccagatccct gaagaagatc gctgttccca ttccaagaaa ctctgtccta 1080ttgacatgct atgggatagc aacaaatgta aatgtgtttt gcaggaggaa aatccacttg 1140ctggaacaga agaccactct catctccagg aaccagctct ctgtgggcca cacatgatgt 1200ttgacgaaga tcgttgcgag tgtgtctgta aaacaccatg tcccaaagat ctaatccagc 1260
accccaaaaa ctgcagttgc tttgagtgca aagaaagtct ggagacctgc tgccagaagc1320acaagctatt tcacccagac acctgcagct gtgaggacag atgccccttt cataccagac1380catgtgcaag tggcaaaaca gcatgtgcaa agcattgccg ctttccaaag gagaaaaggg1440ctgcccaggg gccccacagc cgaaagaatc cttgattcag cgttccaagt tccccatccc1500tgtcattttt aacagcatgc tgctttgcca agttgctgtc actgtttttt tcccaggtgt1560taaaaaaaaa atccatttta cacagcacca cagtgaatcc agaccaacct tccattcaca1620ccagctaagg agtccctggt tcattgatgg atgtcttcta gctgcagatg cctctgcgca1680ccaaggaatg gagaggaggg gacccatgta atccttttgt ttagttttgt ttttgttttt1740tggtgaatga gaaaggtgtg ctggtcatgg aatggcaggt gtcatatgac tgattactca1800gagcagatga ggaaaactgt agtctctgag tcctttgcta atcgcaactc ttgtgaatta1860ttctgattct tttttatgca gaatttgatt cgtatgatca gtactgactt tctgattact1920gtccagctta tagtcttcca gtttaatgaa ctaccatctg atgtttcata tttaagtgta1980tttaaagaaa ataaacacca ttattcaagc caaaaaaaaa aaaaaaaaa2029<210>70<211>354<212>PRT<213>智人(Homo sapiens)<400>70Met Tyr Arg Glu Trp Val Val Val Asn Val Phe Met Met Leu Tyr Val1 5 10 15Gln Leu Val Gln Gly Ser Ser Asn Glu His Gly Pro Val Lys Arg Ser20 25 30Ser Gln Ser Thr Leu Glu Arg Ser Glu Gln Gln Ile Arg Ala Ala Ser35 40 45Ser Leu Glu Glu Leu Leu Arg Ile Thr His Ser Glu Asp Trp Lys Leu50 55 60Trp Arg Cys Arg Leu Arg Leu Lys Ser Phe Thr Ser Met Asp Ser Arg65 70 75 80Ser Ala Ser His Arg Ser Thr Arg Phe Ala Ala Thr Phe Tyr Asp Ile85 90 95Glu Thr Leu Lys Val Ile Asp Glu Glu Trp Gln Arg Thr Gln Cys Ser100 105 110Pro Arg Glu Thr Cys Val Glu Val Ala Ser Glu Leu Gly Lys Ser Thr115 120 125Asn Thr Phe Phe Lys Pro Pro Cys Val Asn Val Phe Arg Cys Gly Gly130 135 140Cys Cys Asn Glu Glu Ser Leu Ile Cys Met Asn Thr Ser Thr Ser Tyr145 150 155 160Ile Ser Lys Gln Leu Phe Glu Ile Ser Val Pro Leu Thr Ser Val Pro165 170 175
Glu Leu Val Pro Val Lys Val Ala Asn His Thr Gly Cys Lys Cys Leu180 185 190Pro Thr Ala Pro Arg His Pro Tyr Ser Ile Ile Arg Arg Ser Ile Gln195 200 205Ile Pro Glu Glu Asp Arg Cys Ser His Ser Lys Lys Leu Cys Pro Ile210 215 220Asp Met Leu Trp Asp Ser Asn Lys Cys Lys Cys Val Leu Gln Glu Glu225 230 235 240Asn Pro Leu Ala Gly Thr Glu Asp His Ser His Leu Gln Glu Pro Ala245 250 255Leu Cys Gly Pro His Met Met Phe Asp Glu Asp Arg Cys Glu Cys Val260 265 270Cys Lys Thr Pro Cys Pro Lys Asp Leu Ile Gln His Pro Lys Asn Cys275 280 285Ser Cys Phe Glu Cys Lys Glu Ser Leu Glu Thr Cys Cys Gln Lys His290 295 300Lys Leu Phe His Pro Asp Thr Cys Ser Cys Glu Asp Arg Cys Pro Phe305 310 315 320His Thr Arg Pro Cys Ala Ser Gly Lys Thr Ala Cys Ala Lys His Cys325 330 335Arg Phe Pro Lys Glu Lys Arg Ala Ala Gln Gly Pro His Ser Arg Lys340 345 350Asn Pro<210>71<211>2825<212>DNA<213>智人(Homo sapiens)<220>
<221>misc_feature<222>(2689)..(2689)<223>n是a，c，g或t<400>71gacgcgtggg cggacgcgtg ggctggttca ggtccaggtt ttgctttgat ccttttcaaa 60aactggagac acagaagagg gctctaggaa aaagttttgg atgggattat gtggaaacta120ccctgcgatt ctctgctgcc agagcaggct cggcgcttcc accccagtgc agccttcccc180
tggcggtggt gaaagagact cgggagtcgc tgcttccaaa gtgcccgccg tgagtgagct 240ctcaccccag tcagccaaat gagcctcttc gggcttctcc tgctgacatc tgccctggcc 300ggccagagac aggggactca ggcggaatcc aacctgagta gtaaattcca gttttccagc 360aacaaggaac agaacggagt acaagatcct cagcatgaga gaattattac tgtgtctact 420aatggaagta ttcacagccc aaggtttcct catacttatc caagaaatac ggtcttggta 480tggagattag tagcagtaga ggaaaatgta tggatacaac ttacgtttga tgaaagattt 540gggcttgaag acccagaaga tgacatatgc aagtatgatt ttgtagaagt tgaggaaccc 600agtgatggaa ctatattagg gcgctggtgt ggttctggta ctgtaccagg aaaacagatt 660tctaaaggaa atcaaattag gataagattt gtatctgatg aatattttcc ttctgaacca 720gggttctgca tccactacaa cattgtcatg ccacaattca cagaagctgt gagtccttca 780gtgctacccc cttcagcttt gccactggac ctgcttaata atgctataac tgcctttagt 840accttggaag accttattcg atatcttgaa ccagagagat ggcagttgga cttagaagat 900ctatataggc caacttggca acttcttggc aaggcttttg tttttggaag aaaatccaga 960gtggtggatc tgaaccttct aacagaggag gtaagattat acagctgcac acctcgtaac1020ttctcagtgt ccataaggga agaactaaag agaaccgata ccattttctg gccaggttgt1080ctcctggtta aacgctgtgg tgggaactgt gcctgttgtc tccacaattg caatgaatgt1140caatgtgtcc caagcaaagt tactaaaaaa taccacgagg tccttcagtt gagaccaaag1200accggtgtca ggggattgca caaatcactc accgacgtgg ccctggagca ccatgaggag1260tgtgactgtg tgtgcagagg gagcacagga ggatagccgc atcaccacca gcagctcttg1320cccagagctg tgcagtgcag tggctgattc tattagagaa cgtatgcgtt atctccatcc1380ttaatctcag ttgtttgctt caaggacctt tcatcttcag gatttacagt gcattctgaa1440agaggagaca tcaaacagaa ttaggagttg tgcaacagct cttttgagag gaggcctaaa1500ggacaggaga aaaggtcttc aatcgtggaa agaaaattaa atgttgtatt aaatagatca1560ccagctagtt tcagagttac catgtacgta ttccactagc tgggttctgt atttcagttc1620tttcgatacg gcttagggta atgtcagtac aggaaaaaaa ctgtgcaagt gagcacctga1680ttccgttgcc ttgcttaact ctaaagctcc atgtcctgggcctaaaatcg tataaaatct 1740ggattttttt tttttttttt gctcatattc acatatgtaa accagaacat tctatgtact1800acaaacctgg tttttaaaaa ggaactatgt tgctatgaat taaacttgtg tcatgctgat1860aggacagact ggatttttca tatttcttat taaaatttct gccatttaga agaagagaac1920tacattcatg gtttggaaga gataaacctg aaaagaagag tggccttatc ttcactttat1980cgataagtca gtttatttgt ttcattgtgt acatttttat attctccttt tgacattata2040actgttggct tttctaatct tgttaaatat atctattttt accaaaggta tttaatattc2100ttttttatga caacttagat caactatttt tagcttggta aatttttcta aacacaattg2160ttatagccag aggaacaaag atgatataaa atattgttgc tctgacaaaa atacatgtat2220ttcattctcg tatggtgcta gagttagatt aatctgcatt ttaaaaaact gaattggaat2280agaattggta agttgcaaag actttttgaa aataattaaa ttatcatatc ttccattcct2340gttattggag atgaaaataa aaagcaactt atgaaagtag acattcagat ccagccatta2400ctaacctatt ccttttttgg ggaaatctga gcctagctca gaaaaacata aagcaccttg2460aaaaagactt ggcagcttcc tgataaagcg tgctgtgctg tgcagtagga acacatccta2520tttattgtga tgttgtggtt ttattatctt aaactctgtt ccatacactt gtataaatac2580atggatattt ttatgtacag aagtatgtct cttaaccagt tcacttattg tactctggca2640atttaaaaga aaatcagtaa aatattttgc ttgtaaaatg cttaatatng tgcctaggtt2700atgtggtgac tatttgaatc aaaaatgtat tgaatcatca aataaaagaa tgtggctatt2760ttggggagaa aattaaaaaa aaaaaaaaaa aaaaaggttt agggataaca gggtaatgcg2820gccgc2825<210>72<211>345<212>PRT<213>智人(Homo sapiens)<400>72
Met Ser Leu Phe Gly Leu Leu Leu Leu Thr Ser Ala Leu Ala Gly Gln1 5 10 15Arg Gln Gly Thr Gln Ala Glu Ser Asn Leu Ser Ser Lys Phe Gln Phe20 25 30Ser Ser Asn Lys Glu Gln Asn Gly Val Gln Asp Pro Gln His Glu Arg35 40 45Ile Ile Thr Val Ser Thr Asn Gly Ser Ile His Ser Pro Arg Phe Pro50 55 60His Thr Tyr Pro Arg Asn Thr Val Leu Val Trp Arg Leu Val Ala Val65 70 75 80Glu Glu Asn Val Trp Ile Gln Leu Thr Phe Asp Glu Arg Phe Gly Leu85 90 95Glu Asp Pro Glu Asp Asp Ile Cys Lys Tyr Asp Phe Val Glu Val Glu100 105 110Glu Pro Ser Asp Gly Thr Ile Leu Gly Arg Trp Cys Gly Ser Gly Thr115 120 125Val Pro Gly Lys Gln Ile Ser Lys Gly Asn Gln Ile Arg Ile Arg Phe130 135 140Val Ser Asp Glu Tyr Phe Pro Ser Glu Pro Gly Phe Cys Ile His Tyr145 150 155 160Asn Ile Val Met Pro Gln Phe Thr Glu Ala Val Ser Pro Ser Val Leu165 170 175Pro Pro Ser Ala Leu Pro Leu Asp Leu Leu Asn Asn Ala Ile Thr Ala180 185 190Phe Ser Thr Leu Glu Asp Leu Ile Arg Tyr Leu Glu Pro Glu Arg Trp195 200 205Gln Leu Asp Leu Glu Asp Leu Tyr Arg Pro Thr Trp Gln Leu Leu Gly210 215 220Lys Ala Phe Val Phe Gly Arg Lys Ser Arg Val Val Asp Leu Asn Leu225 230 235 240Leu Thr Glu Glu Val Arg Leu Tyr Ser Cys Thr Pro Arg Asn Phe Ser245 250 255Val Ser Ile Arg Glu Glu Leu Lys Arg Thr Asp Thr Ile Phe Trp Pro260 265 270Gly Cys Leu Leu Val Lys Arg Cys Gly Gly Asn Cys Ala Cys Cys Leu
275 280 285His Asn Cys Asn Glu Cys Gln Cys Val Pro Ser Lys Val Thr Lys Lys290 295 300Tyr His Glu Val Leu Gln Leu Arg Pro Lys Thr Gly Val Arg Gly Leu305 310 315 320His Lys Ser Leu Thr Asp Val Ala Leu Glu His His Glu Glu Cys Asp325 330 335Cys Val Cys Arg Gly Ser Thr Gly Gly340 345<210>73<211>2745<212>DNA<213>智人(Homo sapiens)<400>73acctccctcc gcggagcagc cagacagcga gggccccggc cgggggcagg ggggacgccc 60cgtccggggc accccccccg gctctgagcc gcccgcgggg ccggcctcgg cccggagcgg120aggaaggagt cgccgaggag cagcctgagg ccccagagtc tgagacgagc cgccgccgcc180cccgccactg cggggaggag ggggaggagg agcgggagga gggacgagct ggtcgggaga240agaggaaaaa aacttttgag acttttccgt tgccgctggg agccggaggc gcggggacct300cttggcgcga cgctgccccg cgaggaggca ggacttgggg accccagacc gcctcccttt360gccgccgggg acgcttgctc cctccctgcc ccctacacgg cgtccctcag gcgcccccat420tccggaccag ccctcgggag tcgccgaccc ggcctcccgc aaagactttt ccccagacct480cgggcgcacc ccctgcacgc cgccttcatc cccggcctgt ctcctgagcc cccgcgcatc540ctagaccctt tctcctccag gagacggatc tctctccgac ctgccacaga tcccctattc600aagaccaccc accttctggt accagatcgc gcccatctag gttatttccg tgggatactg660agacaccccc ggtccaagcc tcccctccac cactgcgccc ttctccctga ggagcctcag720ctttccctcg aggccctcct accttttgcc gggagacccc cagcccctgc aggggcgggg780cctccccacc acaccagccc tgttcgcgct ctcggcagtg ccggggggcg ccgcctcccc840catgccgccc tccgggctgc ggctgctgcc gctgctgcta ccgctgctgt ggctactggt900gctgacgcct ggcccgccgg ccgcgggact atccacctgc aagactatcg acatggagct960ggtgaagcgg aagcgcatcg aggccatccg cggccagatc ctgtccaagc tgcggctcgc 1020cagccccccg agccaggggg aggtgccgcc cggcccgctg cccgaggccg tgctcgccct 1080gtacaacagc acccgcgacc gggtggccgg ggagagtgca gaaccggagc ccgagcctga 1140ggccgactac tacgccaagg aggtcacccg cgtgctaatg gtggaaaccc acaacgaaat 1200ctatgacaag ttcaagcaga gtacacacag catatatatg ttcttcaaca catcagagct 1260ccgagaagcg gtacctgaac ccgtgttgct ctcccgggca gagctgcgtc tgctgaggag 1320gctcaagtta aaagtggagc agcacgtgga gctgtaccag aaatacagca acaattcctg 1380gcgatacctc agcaaccggc tgctggcacc cagcgactcg ccagagtggt tatcttttga 1440tgtcaccgga gttgtgcggc agtggttgag ccgtggaggg gaaattgagg gctttcgcct 1500tagcgcccac tgctcctgtg acagcaggga taacacactg caagtggaca tcaacgggtt 1560cactaccggc cgccgaggtg acctggccac cattcatggc atgaaccggc ctttcctgct 1620tctcatggcc accccgctgg agagggccca gcatctgcaa agctcccggc accgccgagc 1680cctggacacc aactattgct tcagctccac ggagaagaac tgctgcgtgc ggcagctgta 1740cattgacttc cgcaaggacc tcggctggaa gtggatccac gagcccaagg gctaccatgc 1800caacttctgc ctcgggccct gcccctacat ttggagcctg gacacgcagt acagcaaggt 1860cctggccctg tacaaccagc ataacccggg cgcctcggcg gcgccgtgct gcgtgccgca 1920
ggcgctggag ccgctgccca tcgtgtacta cgtgggccgc aagcccaagg tggagcagct 1980gtccaacatg atcgtgcgct cctgcaagtg cagctgaggt cccgccccgc cccgccccgc 2040cccggcaggc ccggccccac cccgccccgc ccccgctgcc ttgcccatgg gggctgtatt 2100taaggacacc gtgccccaag cccacctggg gccccattaa agatggagag aggactgcgg 2160atctctgtgt cattgggcgc ctgcctgggg tctccatccc tgacgttccc ccactcccac 2220tccctctctc tccctctctg cctcctcctg cctgtctgca ctattccttt gcccggcatc 2280aaggcacagg ggaccagtgg ggaacactac tgtagttaga tctatttatt gagcaccttg 2340ggcactgttg aagtgcctta cattaatgaa ctcattcagt caccatagca acactctgag 2400atggcaggga ctctgataac acccatttta aaggttgagg aaacaagccc agagaggtta 2460agggaggagt tcctgcccac caggaacctg ctttagtggg ggatagtgaa gaagacaata 2520aaagatagta gttcaggcca ggcggggtgc tcacgcctgt aatcctagca cttttgggag 2580gcagagatgg gaggatactt gaatccaggc atttgagacc agcctgggta acatagtgag 2640accctatctc tacaaaacac ttttaaaaaa tgtacacctg tggtcccagc tactctggag 2700gctaaggtgg gaggatcact tgatcctggg aggtcaaggc tgcag 2745<210>74<211>391<212>PRT<213>智人(Homo sapiens)<400>74Met Pro Pro Ser Gly Leu Arg Leu Leu Pro Leu Leu Leu Pro Leu Leu1 5 10 15Trp Leu Leu Val Leu Thr Pro Gly Pro Pro Ala Ala Gly Leu Ser Thr20 25 30Cys Lys Thr Ile Asp Met Glu Leu Val Lys Arg Lys Arg Ile Glu Ala35 40 45Ile Arg Gly Gln Ile Leu Ser Lys Leu Arg Leu Ala Ser Pro Pro Ser50 55 60Gln Gly Glu Val Pro Pro Gly Pro Leu Pro Glu Ala Val Leu Ala Leu65 70 75 80Tyr Asn Ser Thr Arg Asp Arg Val Ala Gly Glu Ser Ala Glu Pro Glu85 90 95Pro Glu Pro Glu Ala Asp Tyr Tyr Ala Lys Glu Val Thr Arg Val Leu100 105 110Met Val Glu Thr His Asn Glu Ile Tyr Asp Lys Phe Lys Gln Ser Thr115 120 125His Ser Ile Tyr Met Phe Phe Asn Thr Ser Glu Leu Arg Glu Ala Val130 135 140Pro Glu Pro Val Leu Leu Ser Arg Ala Glu Leu Arg Leu Leu Arg Arg145 150 155 160Leu Lys Leu Lys Val Glu Gln His Val Glu Leu Tyr Gln Lys Tyr Ser
165 170 175Asn Asn Ser Trp Arg Tyr Leu Ser Asn Arg Leu Leu Ala Pro Ser Asp180 185 190Ser Pro Glu Trp Leu Ser Phe Asp Val Thr Gly Val Val Arg Gln Trp195 200 205Leu Ser Arg Gly Gly Glu Ile Glu Gly Phe Arg Leu Ser Ala His Cys210 215 220Ser Cys Asp Ser Arg Asp Asn Thr Leu Gln Val Asp Ile Asn Gly Phe225 230 235 240Thr Thr Gly Arg Arg Gly Asp Leu Ala Thr Ile His Gly Met Asn Arg245 250 255Pro Phe Leu Leu Leu Met Ala Thr Pro Leu Glu Arg Ala Gln His Leu260 265 270Gln Ser Ser Arg His Arg Arg Ala Leu Asp Thr Asn Tyr Cys Phe Ser275 280 285Ser Thr Glu Lys Asn Cys Cys Val Arg Gln Leu Tyr Ile Asp Phe Arg290 295 300Lys Asp Leu Gly Trp Lys Trp Ile His Glu Pro Lys Gly Tyr His Ala305 310 315 320Asn Phe Cys Leu Gly Pro Cys Pro Tyr Ile Trp Ser Leu Asp Thr Gln325 330 335Tyr Ser Lys Val Leu Ala Leu Tyr Asn Gln His Asn Pro Gly Ala Ser340 345 350Ala Ala Pro Cys Cys Val Pro Gln Ala Leu Glu Pro Leu Pro Ile Val355 360 365Tyr Tyr Val Gly Arg Lys Pro Lys Val Glu Gln Leu Ser Asn Met Ile370 375 380Val Arg Ser Cys Lys Cys Ser385 390<210>75<211>336<212>DNA<213>智人(Homo sapiens)<400>75gccctggaca ccaactattg cttcagctcc acggagaaga actgctgcgt gcggcagctg 60tacattgact tccgcaagga cctcggctgg aagtggatcc acgagcccaa gggctaccat120
gccaacttct gcctcgggcc ctgcccctac atttggagcc tggacacgca gtacagcaag 180gtcctggccc tgtacaacca gcataacccg ggcgcctcgg cggcgccgtg ctgcgtgccg 240caggcgctgg agccgctgcc catcgtgtac tacgtgggcc gcaagcccaa ggtggagcag 300ctgtccaaca tgatcgtgcg ctcctgcaag tgcagc 336<210>76<211>112<212>PRT<213>智人(Homo sapiens)<400>76Ala Leu Asp Thr Asn Tyr Cys Phe Ser Ser Thr Glu Lys Asn Cys Cys1 5 10 15Val Arg Gln Leu Tyr Ile Asp Phe Arg Lys Asp Leu Gly Trp Lys Trp20 25 30Ile His Glu Pro Lys Gly Tyr His Ala Asn Phe Cys Leu Gly Pro Cys35 40 45Pro Tyr Ile Trp Ser Leu Asp Thr Gln Tyr Ser Lys Val Leu Ala Leu50 55 60Tyr Asn Gln His Asn Pro Gly Ala Ser Ala Ala Pro Cys Cys Val Pro65 70 75 80Gln Ala Leu Glu Pro Leu Pro Ile Val Tyr Tyr Val Gly Arg Lys Pro85 90 95Lys Val Glu Gln Leu Ser Asn Met Ile Val Arg Ser Cys Lys Cys Ser100 105 110<210>77<211>1695<212>DNA<213>智人(Homo sapiens)<400>77caagcaggat acgtttttct gttgggcatt gactagattg tttgcaaaag tttcgcatca 60aaaacaaaca acaacaacaa aaaaccaaac aactctcctt gatctatact ttgagaattg120ttgatttctt tttttttatt ctgactttta aaaacaactt ttttttccac ttttttaaaa180aatgcactac tgtgtgctga gcgcttttct gatcctgcat ctggtcacgg tcgcgctcag240cctgtctacc tgcagcacac tcgatatgga ccagttcatg cgcaagagga tcgaggcgat300ccgcgggcag atcctgagca agctgaagct caccagtccc ccagaagact atcctgagcc360cgaggaagtc cccccggagg tgatttccat ctacaacagc accagggact tgctccagga420gaaggcgagc cggagggcgg ccgcctgcga gcgcgagagg agcgacgaag agtactacgc480caaggaggtt tacaaaatag acatgccgcc cttcttcccc tccgaaaatg ccatcccgcc540cactttctac agaccctact tcagaattgt tcgatttgac gtctcagcaa tggagaagaa600tgcttccaat ttggtgaaag cagagttcag agtctttcgt ttgcagaacc caaaagccag660agtgcctgaa caacggattg agctatatca gattctcaag tccaaagatt taacatctcc720aacccagcgc tacatcgaca gcaaagttgt gaaaacaaga gcagaaggcg aatggctctc780cttcgatgta actgatgctg ttcatgaatg gcttcaccat aaagacagga acctgggatt840
taaaataagc ttacactgtc cctgctgcac ttttgtacca tctaataatt acatcatccc 900aaataaaagt gaagaactag aagcaagatt tgcaggtatt gatggcacct ccacatatac 960cagtggtgat cagaaaacta taaagtccac taggaaaaaa aacagtggga agaccccaca 1020tctcctgcta atgttattgc cctcctacag acttgagtca caacagacca accggcggaa 1080gaagcgtgct ttggatgcgg cctattgctt tagaaatgtg caggataatt gctgcctacg 1140tccactttac attgatttca agagggatct agggtggaaa tggatacacg aacccaaagg 1200gtacaatgcc aacttctgtg ctggagcatg cccgtattta tggagttcag acactcagca 1260cagcagggtc ctgagcttat ataataccat aaatccagaa gcatctgctt ctccttgctg 1320cgtgtcccaa gatttagaac ctctaaccat tctctactac attggcaaaa cacccaagat 1380tgaacagctt tctaatatga ttgtaaagtc ttgcaaatgc agctaaaatt cttggaaaag 1440tggcaagacc aaaatgacaa tgatgatgat aatgatgatg acgacgacaa cgatgatgct 1500tgtaacaaga aaacataaga gagccttggt tcatcagtgt taaaaaattt ttgaaaaggc 1560ggtactagtt cagacacttt ggaagtttgt gttctgtttg ttaaaactgg catctgacac 1620aaaaaaagtt gaaggcctta ttctacattt cacctacttt gtaagtgaga gagacaagaa 1680gcaaattttt ttaaa 1695<210>78<211>414<212>PRT<213>智人(Homo sapiens)<400>78Met His Tyr Cys Val Leu Ser Ala Phe Leu Ile Leu His Leu Val Thr1 5 10 15Val Ala Leu Ser Leu Ser Thr Cys Ser Thr Leu Asp Met Asp Gln Phe20 25 30Met Arg Lys Arg Ile Glu Ala Ile Arg Gly Gln Ile Leu Ser Lys Leu35 40 45Lys Leu Thr Ser Pro Pro Glu Asp Tyr Pro Glu Pro Glu Glu Val Pro50 55 60Pro Glu Val Ile Ser Ile Tyr Asn Ser Thr Arg Asp Leu Leu Gln Glu65 70 75 80Lys Ala Ser Arg Arg Ala Ala Ala Cys Glu Arg Glu Arg Ser Asp Glu85 90 95Glu Tyr Tyr Ala Lys Glu Val Tyr Lys Ile Asp Met Pro Pro Phe Phe100 105 110Pro Ser Glu Asn Ala Ile Pro Pro Thr Phe Tyr Arg Pro Tyr Phe Arg115 120 125Ile Val Arg Phe Asp Val Ser Ala Met Glu Lys Asn Ala Ser Asn Leu130 135 140Val Lys Ala Glu Phe Arg Val Phe Arg Leu Gln Asn Pro Lys Ala Arg145 150 155 160
Val Pro Glu Gln Arg Ile Glu Leu Tyr Gln Ile Leu Lys Ser Lys Asp165 170 175Leu Thr Ser Pro Thr Gln Arg Tyr Ile Asp Ser Lys Val Val Lys Thr180 185 190Arg Ala Glu Gly Glu Trp Leu Ser Phe Asp Val Thr Asp Ala Val His195 200 205Glu Trp Leu His His Lys Asp Arg Asn Leu Gly Phe Lys Ile Ser Leu210 215 220His Cys Pro Cys Cys Thr Phe Val Pro Ser Asn Asn Tyr Ile Ile Pro225 230 235 240Ash Lys Ser Glu Glu Leu Glu Ala Arg Phe Ala Gly Ile Asp Gly Thr245 250 255Ser Thr Tyr Thr Ser Gly Asp Gln Lys Thr Ile Lys Ser Thr Arg Lys260 265 270Lys Asn Ser Gly Lys Thr Pro His Leu Leu Leu Met Leu Leu Pro Ser275 280 285Tyr Arg Leu Glu Ser Gln Gln Thr Asn Arg Arg Lys Lys Arg Ala Leu290 295 300Asp Ala Ala Tyr Cys Phe Arg Asn Val Gln Asp Asn Cys Cys Leu Arg305 310 315 320Pro Leu Tyr Ile Asp Phe Lys Arg Asp Leu Gly Trp Lys Trp Ile His325 330 335Glu Pro Lys Gly Tyr Asn Ala Asn Phe Cys Ala Gly Ala Cys Pro Tyr340 345 350Leu Trp Ser Ser Asp Thr Gln His Ser Arg Val Leu Ser Leu Tyr Asn355 360 365Thr Ile Asn Pro Glu Ala Ser Ala Ser Pro Cys Cys Val Ser Gln Asp370 375 380Leu Glu Pro Leu Thr Ile Leu Tyr Tyr Ile Gly Lys Thr Pro Lys Ile385 390 395 400Glu Gln Leu Ser Asn Met Ile Val Lys Ser Cys Lys Cys Ser405 410<210>79<211>336<212>DNA<213>智人(Homo sapiens)
<400>79gctttggatg cggcctattg ctttagaaat gtgcaggata attgctgcct acgtccactt 60tacattgatt tcaagaggga tctagggtgg aaatggatac acgaacccaa agggtacaat120gccaacttct gtgctggagc atgcccgtat ttatggagtt cagacactca gcacagcagg180gtcctgagct tatataatac cataaatcca gaagcatctg cttctccttg ctgcgtgtcc240caagatttag aacctctaac cattctctac tacattggca aaacacccaa gattgaacag300ctttctaata tgattgtaaa gtcttgcaaa tgcagc 336<210>80<211>112<212>PRT<213>智人(Homo sapiens)<400>80Ala Leu Asp Ala Ala Tyr Cys Phe Arg Asn Val Gln Asp Asn Cys Cys1 5 10 15Leu Arg Pro Leu Tyr Ile Asp Phe Lys Arg Asp Leu Gly Trp Lys Trp20 25 30Ile His Glu Pro Lys Gly Tyr Asn Ala Asn Phe Cys Ala Gly Ala Cys35 40 45Pro Tyr Leu Trp Ser Ser Asp Thr Gln His Ser Arg Val Leu Ser Leu50 55 60Tyr Asn Thr Ile Asn Pro Glu Ala Ser Ala Ser Pro Cys Cys Val Ser65 70 75 80Gln Asp Leu Glu Pro Leu Thr Ile Leu Tyr Tyr Ile Gly Lys Thr Pro85 90 95Lys Ile Glu Gln Leu Ser Asn Met Ile Val Lys Ser Cys Lys Cys Ser100 105 110<210>81<211>2574<212>DNA<213>智人(Homo sapiens)<400>81cctgtttaga cacatggaca acaatcccag cgctacaagg cacacagtcc gcttcttcgt 60cctcagggtt gccagcgctt cctggaagtc ctgaagctct cgcagtgcag tgagttcatg120caccttcttg ccaagcctca gtctttggga tctggggagg ccgcctggtt ttcctccctc180cttctgcacg tctgctgggg tctcttcctc tccaggcctt gccgtccccc tggcctctct240tcccagctca cacatgaaga tgcacttgca aagggctctg gtggtcctgg ccctgctgaa300ctttgccacg gtcagcctct ctctgtccac ttgcaccacc ttggacttcg gccacatcaa360gaagaagagg gtggaagcca ttaggggaca gatcttgagc aagctcaggc tcaccagccc420ccctgagcca acggtgatga cccacgtccc ctatcaggtc ctggcccttt acaacagcac480ccgggagctg ctggaggaga tgcatgggga gagggaggaa ggctgcaccc aggaaaacac540cgagtcggaa tactatgcca aagaaatcca taaattcgac atgatccagg ggctggcgga600
gcacaacgaa ctggctgtct gccctaaagg aattacctcc aaggttttcc gcttcaatgt 660gtcctcagtg gagaaaaata gaaccaacct attccgagca gaattccggg tcttgcgggt 720gcccaacccc agctctaagc ggaatgagca gaggatcgag ctcttccaga tccttcggcc 780agatgagcac attgccaaac agcgctatat cggtggcaag aatctgccca cacggggcac 840tgccgagtgg ctgtcctttg atgtcactga cactgtgcgt gagtggctgt tgagaagaga 900gtccaactta ggtctagaaa tcagcattca ctgtccatgt cacacctttc agcccaatgg 960agatatcctg gaaaacattc acgaggtgat ggaaatcaaa ttcaaaggcg tggacaatga 1020ggatgaccat ggccgtggag atctggggcg cctcaagaag cagaaggatc accacaaccc 1080tcatctaatc ctcatgatga ttcccccaca ccggctcgac aacccgggcc aggggggtca 1140gaggaagaag cgggctttgg acaccaatta ctgcttccgc aacttggagg agaactgctg 1200tgtgcgcccc ctctacattg acttccgaca ggatctgggc tggaagtggg tccatgaacc 1260taagggctac tatgccaact tctgctcagg cccttgccca tacctccgca gtgcagacac 1320aacccacagc acggtgctgg gactgtacaa cactctgaac cctgaagcat ctgcctcgcc 1380ttgctgcgtg ccccaggacc tggagcccct gaccatcctg tactatgttg ggaggacccc 1440caaagtggag cagctctcca acatggtggt gaagtcttgt aaatgtagct gagaccccac 1500gtgcgacaga gagaggggag agagaaccac cactgcctga ctgcccgctc ctcgggaaac 1560acacaagcaa caaacctcac tgagaggcct ggagcccaca accttcggct ccgggcaaat 1620ggctgagatg gaggtttcct tttggaacat ttctttcttg ctggctctga gaatcacggt 1680ggtaaagaaa gtgtgggttt ggttagagga aggctgaact cttcagaaca cacagacttt 1740ctgtgacgca gacagagggg atggggatag aggaaaggga tggtaagttg agatgttgtg 1800tggcaatggg atttgggcta ccctaaaggg agaaggaagg gcagagaatg gctgggtcag 1860ggccagactg gaagacactt cagatctgag gttggatttg ctcattgctg taccacatct 1920gctctaggga atctggatta tgttatacaa ggcaagcatt ttttttttta aagacaggtt 1980acgaagacaa agtcccagaa ttgtatctca tactgtctgg gattaagggc aaatctatta 2040cttttgcaaa ctgtcctcta catcaattaa catcgtgggt cactacaggg agaaaatcca 2100ggtcatgcag ttcctggccc atcaactgta ttgggccttt tggatatgct gaacgcagaa 2160gaaagggtgg aaatcaaccc tctcctgtct gccctctggg tccctcctct cacctctccc 2220tcgatcatat ttccccttgg acacttggtt agacgccttc caggtcagga tgcacatttc 2280tggattgtgg ttccatgcag ccttggggca ttatgggtct tcccccactt cccctccaag 2340accctgtgtt catttggtgt tcctggaagc aggtgctaca acatgtgagg cattcgggga 2400agctgcacat gtgccacaca gtgacttggc cccagacgca tagactgagg tataaagaca 2460agtatgaata ttactctcaa aatctttgta taaataaata tttttggggc atcctggatg 2520atttcatctt ctggaatatt gtttctagaa cagtaaaagc cttattctaa ggtg2574<210>82<21l>412<212>PRT<213>智人(Homo sapiens)<400>82Met Lys Met His Leu Gln Arg Ala Leu Val Val Leu Ala Leu Leu Asn1 5 10 15Phe Ala Thr Val Ser Leu Ser Leu Ser Thr Cys Thr Thr Leu Asp Phe20 25 30Gly His Ile Lys Lys Lys Arg Val Glu Ala Ile Arg Gly Gln Ile Leu35 40 45Ser Lys Leu Arg Leu Thr Ser Pro Pro Glu Pro Thr Val Met Thr His50 55 60
Val Pro Tyr Gln Val Leu Ala Leu Tyr Asn Ser Thr Arg Glu Leu Leu65 70 75 80Glu Glu Met His Gly Glu Arg Glu Glu Gly Cys Thr Gln Glu Asn Thr85 90 95Glu Ser Glu Tyr Tyr Ala Lys Glu Ile His Lys Phe Asp Met Ile Gln100 105 110Gly Leu Ala Glu His Asn Glu Leu Ala Val Cys Pro Lys Gly Ile Thr115 120 125Ser Lys Val Phe Arg Phe Asn Val Ser Ser Val Glu Lys Asn Arg Thr130 135 140Asn Leu Phe Arg Ala Glu Phe Arg Val Leu Arg Val Pro Asn Pro Ser145 150 155 160Ser Lys Arg Asn Glu Gln Arg Ile Glu Leu Phe Gln Ile Leu Arg Pro165 170 175Asp Glu His Ile Ala Lys Gln Arg Tyr Ile Gly Gly Lys Asn Leu Pro180 185 190Thr Arg Gly Thr Ala Glu Trp Leu Ser Phe Asp Val Thr Asp Thr Val195 200 205Arg Glu Trp Leu Leu Arg Arg Glu Ser Asn Leu Gly Leu Glu Ile Ser210 215 220Ile His Cys Pro Cys His Thr Phe Gln Pro Asn Gly Asp Ile Leu Glu225 230 235 240Asn Ile His Glu Val Met Glu Ile Lys Phe Lys Gly Val Asp Asn Glu245 250 255Asp Asp His Gly Arg Gly Asp Leu Gly Arg Leu Lys Lys Gln Lys Asp260 265 270His His Asn Pro His Leu Ile Leu Met Met Ile Pro Pro His Arg Leu275 280 285Asp Asn Pro Gly Gln Gly Gly Gln Arg Lys Lys Arg Ala Leu Asp Thr290 295 300Asn Tyr Cys Phe Arg Asn Leu Glu Glu Asn Cys Cys Val Arg Pro Leu305 310 315 320Tyr Ile Asp Phe Arg Gln Asp Leu Gly Trp Lys Trp Val His Glu Pro325 330 335Lys Gly Tyr Tyr Ala Asn Phe Cys Ser Gly Pro Cys Pro Tyr Leu Arg
340 345 350Ser Ala Asp Thr Thr His Ser Thr Val Leu Gly Leu Tyr Asn Thr Leu355 360 365Asn Pro Glu Ala Ser Ala Ser Pro Cys Cys Val Pro Gln Asp Leu Glu370 375 380Pro Leu Thr Ile Leu Tyr Tyr Val Gly Arg Thr Pro Lys Val Glu Gln385 390 395 400Leu Ser Asn Met Val Val Lys Ser Cys Lys Cys Ser405 410<210>83<211>3213<212>DNA<213>智人(Homo sapiens)<400>83agagactcaa gatgattccc tttttaccca tgttttctct actattgctg cttattgtta 60accctataaa cgccaacaat cattatgaca agatcttggc tcatagtcgt atcaggggtc120gggaccaagg cccaaatgtc tgtgcccttc aacagatttt gggcaccaaa aagaaatact180tcagcacttg taagaactgg tataaaaagt ccatctgtgg acagaaaacg actgttttat240atgaatgttg ccctggttat atgagaatgg aaggaatgaa aggctgccca gcagttttgc300ccattgacca tgtttatggc actctgggca tcgtgggagc caccacaacg cagcgctatt360ctgacgcctc aaaactgagg gaggagatcg agggaaaggg atccttcact tactttgcac420cgagtaatga ggcttgggac aacttggatt ctgatatccg tagaggtttg gagagcaacg480tgaatgttga attactgaat gctttacata gtcacatgat taataagaga atgttgacca540aggacttaaa aaatggcatg attattcctt caatgtataa caatttgggg cttttcatta600accattatcc taatggggtt gtcactgtta attgtgctcg aatcatccat gggaaccaga660ttgcaacaaa tggtgttgtc catgtcattg accgtgtgct tacacaaatt ggtacctcaa720ttcaagactt cattgaagca gaagatgacc tttcatcttt tagagcagct gccatcacat780cggacatatt ggaggccctt ggaagagacg gtcacttcac actctttgct cccaccaatg840aggcttttga gaaacttcca cgaggtgtcc tagaaaggtt catgggagac aaagtggctt900ccgaagctct tatgaagtac cacatcttaa atactctcca gtgttctgag tctattatgg960gaggagcagt ctttgagacg ctggaaggaa atacaattga gataggatgt gacggtgaca 1020gtataacagt aaatggaatc aaaatggtga acaaaaagga tattgtgaca aataatggtg 1080tgatccattt gattgatcag gtcctaattc ctgattctgc caaacaagtt attgagctgg 1140ctggaaaaca gcaaaccacc ttcacggatc ttgtggccca attaggcttg gcatctgctc 1200tgaggccaga tggagaatac actttgctgg cacctgtgaa taatgcattt tctgatgata 1260ctctcagcat ggttcagcgc ctccttaaat taattctgca gaatcacata ttgaaagtaa 1320aagttggcct taatgagctt tacaacgggc aaatactgga aaccatcgga ggcaaacagc 1380tcagagtctt cgtatatcgt acagctgtct gcattgaaaa ttcatgcatg gagaaaggga 1440gtaagcaagg gagaaacggt gcgattcaca tattccgcga gatcatcaag ccagcagaga 1500aatccctcca tgaaaagtta aaacaagata agcgctttag caccttcctc agcctacttg 1560aagctgcaga cttgaaagag ctcctgacac aacctggaga ctggacatta tttgtgccaa 1620ccaatgatgc ttttaaggga atgactagtg aagaaaaaga aattctgata cgggacaaaa 1680atgctcttca aaacatcatt ctttatcacc tgacaccagg agttttcatt ggaaaaggat 1740ttgaacctgg tgttactaac attttaaaga ccacacaagg aagcaaaatc tttctgaaag 1800aagtaaatga tacacttctg gtgaatgaat tgaaatcaaa agaatctgac atcatgacaa 1860caaatggtgt aattcatgtt gtagataaac tcctctatcc agcagacaca cctgttggaa 1920
atgatcaact gctggaaata cttaataaat taatcaaata catccaaatt aagtttgttc 1980gtggtagcac cttcaaagaa atccccgtga ctgtctatac aactaaaatt ataaccaaag 2040ttgtggaacc aaaaattaaa gtgattgaag gcagtcttca gcctattatc aaaactgaag 2100gacccacact aacaaaagtc aaaattgaag gtgaacctga attcagactg attaaagaag 2160gtgaaacaat aactgaagtg atccatggag agccaattat taaaaaatac accaaaatca 2220ttgatggagt gcctgtggaa ataactgaaa aagagacacg agaagaacga atcattacag 2280gtcctgaaat aaaatacact aggatttcta ctggaggtgg agaaacagaa gaaactctga 2340agaaattgtt acaagaagag gtcaccaagg tcaccaaatt cattgaaggt ggtgatggtc 2400atttatttga agatgaagaa attaaaagac tgcttcaggg agacacaccc gtgaggaagt 2460tgcaagccaa caaaaaagtt caaggttcta gaagacgatt aagggaaggt cgttctcagt 2520gaaaatccaa aaaccagaaa aaaatgttta tacaacccta agtcaataac ctgaccttag 2580aaaattgtga gagccaagtt gacttcagga actgaaacat cagcacaaag aagcaatcat 2640caaataattc tgaacacaaa tttaatattt ttttttctga atgagaaaca tgagggaaat 2700tgtggagtta gcctcctgtg gtaaaggaat tgaagaaaat ataacacctt acaccctttt 2760tcatcttgac attaaaagtt ctggctaact ttggaatcca ttagagaaaa atccttgtca 2820ccagattcat tacaattcaa atcgaagagt tgtgaactgt tatcccattg aaaagaccga 2880gccttgtatg tatgttatgg atacataaaa tgcacgcaag ccattatctc tccatgggaa 2940gctaagttat aaaaataggt gcttggtgta caaaactttt tatatcaaaa ggctttgcac 3000atttctatat gagtgggttt actggtaaat tatgttattt tttacaacta attttgtact 3060ctcagaatgt ttgtcatatg cttcttgcaa tgcatatttt ttaatctcaa acgtttcaat 3120aaaaccattt ttcagatata aagagaatta cttcaaattg agtaattcag aaaaactcaa 3180gatttaagtt aaaaagtggt ttggacttgg gaa 3213<210>84<211>836<212>PRT<213>智人(Homo sapiens)<400>84Met Ile Pro Phe Leu Pro Met Phe Ser Leu Leu Leu Leu Leu Ile Val1 5 10 15Asn Pro Ile Asn Ala Asn Asn His Tyr Asp Lys Ile Leu Ala His Ser20 25 30Arg Ile Arg Gly Arg Asp Gln Gly Pro Asn Val Cys Ala Leu Gln Gln35 40 45Ile Leu Gly Thr Lys Lys Lys Tyr Phe Ser Thr Cys Lys Asn Trp Tyr50 55 60Lys Lys Ser Ile Cys Gly Gln Lys Thr Thr Val Leu Tyr Glu Cys Cys65 70 75 80Pro Gly Tyr Met Arg Met Glu Gly Met Lys Gly Cys Pro Ala Val Leu85 90 95Pro Ile Asp His Val Tyr Gly Thr Leu Gly Ile Val Gly Ala Thr Thr100 105 110Thr Gln Arg Tyr Ser Asp Ala Ser Lys Leu Arg Glu Glu Ile Glu Gly115 120 125
Lys Gly Ser Phe Thr Tyr Phe Ala Pro Ser Asn Glu Ala Trp Asp Asn130 135 140Leu Asp Ser Asp Ile Arg Arg Gly Leu Glu Ser Asn Val Asn Val Glu145 150 155 160Leu Leu Asn Ala Leu His Ser His Met Ile Asn Lys Arg Met Leu Thr165 170 175Lys Asp Leu Lys Asn Gly Met Ile Ile Pro Ser Met Tyr Asn Asn Leu180 185 190Gly Leu Phe Ile Asn His Tyr Pro Asn Gly Val Val Thr Val Asn Cys195 200 205Ala Arg Ile Ile His Gly Asn Gln Ile Ala Thr Asn Gly Val Val His210 215 220Val Ile Asp Arg Val Leu Thr Gln Ile Gly Thr Ser Ile Gln Asp Phe225 230 235 240Ile Glu Ala Glu Asp Asp Leu Ser Ser Phe Arg Ala Ala Ala Ile Thr245 250 255Ser Asp Ile Leu Glu Ala Leu Gly Arg Asp Gly His Phe Thr Leu Phe260 265 270Ala Pro Thr Asn Glu Ala Phe Glu Lys Leu Pro Arg Gly Val Leu Glu275 280 285Arg Phe Met Gly Asp Lys Val Ala Ser Glu Ala Leu Met Lys Tyr His290 295 300Ile Leu Asn Thr Leu Gln Cys Ser Glu Ser Ile Met Gly Gly Ala Val305 310 315 320Phe Glu Thr Leu Glu Gly Asn Thr Ile Glu Ile Gly Cys Asp Gly Asp325 330 335Ser Ile Thr Val Asn Gly Ile Lys Met Val Asn Lys Lys Asp Ile Val340 345 350Thr Asn Asn Gly Val Ile His Leu Ile Asp Gln Val Leu Ile Pro Asp355 360 365Ser Ala Lys Gln Val Ile Glu Leu Ala Gly Lys Gln Gln Thr Thr Phe370 375 380Thr Asp Leu Val Ala Gln Leu Gly Leu Ala Ser Ala Leu Arg Pro Asp385 390 395 400
Gly Glu Tyr Thr Leu Leu Ala Pro Val Asn Asn Ala Phe Ser Asp Asp405 410 415Thr Leu Ser Met Val Gln Arg Leu Leu Lys Leu Ile Leu Gln Asn His420 425 430Ile Leu Lys Val Lys Val Gly Leu Asn Glu Leu Tyr Asn Gly Gln Ile435 440 445Leu Glu Thr Ile Gly Gly Lys Gln Leu Arg Val Phe Val Tyr Arg Thr450 455 460Ala Val Cys Ile Glu Asn Ser Cys Met Glu Lys Gly Ser Lys Gln Gly465 470 475 480Arg Asn Gly Ala Ile His Ile Phe Arg Glu Ile Ile Lys Pro Ala Glu485 490 495Lys Ser Leu His Glu Lys Leu Lys Gln Asp Lys Arg Phe Ser Thr Phe500 505 510Leu Ser Leu Leu Glu Ala Ala Asp Leu Lys Glu Leu Leu Thr Gln Pro515 520 525Gly Asp Trp Thr Leu Phe Val Pro Thr Asn Asp Ala Phe Lys Gly Met530 535 540Thr Ser Glu Glu Lys Glu Ile Leu Ile Arg Asp Lys Asn Ala Leu Gln545 550 555 560Asn Ile Ile Leu Tyr His Leu Thr Pro Gly Val Phe Ile Gly Lys Gly565 570 575Phe Glu Pro Gly Val Thr Asn Ile Leu Lys Thr Thr Gln Gly Ser Lys580 585 590Ile Phe Leu Lys Glu Val Asn Asp Thr Leu Leu Val Asn Glu Leu Lys595 600 605Ser Lys Glu Ser Asp Ile Met Thr Thr Asn Gly Val Ile His Val Val610 615 620Asp Lys Leu Leu Tyr Pro Ala Asp Thr Pro Val Gly Asn Asp Gln Leu625 630 635 640Leu Glu Ile Leu Asn Lys Leu Ile Lys Tyr Ile Gln Ile Lys Phe Val645 650 655Arg Gly Ser Thr Phe Lys Glu Ile Pro Val Thr Val Tyr Thr Thr Lys660 665 670Ile Ile Thr Lys Val Val Glu Pro Lys Ile Lys Val Ile Glu Gly Ser
675 680 685Leu Gln Pro Ile Ile Lys Thr Glu Gly Pro Thr Leu Thr Lys Val Lys690 695 700Ile Glu Gly Glu Pro Glu Phe Arg Leu Ile Lys Glu Gly Glu Thr Ile705 710 715 720Thr Glu Val Ile His Gly Glu Pro Ile Ile Lys Lys Tyr Thr Lys Ile725 730 735Ile Asp Gly Val Pro Val Glu Ile Thr Glu Lys Glu Thr Arg Glu Glu740 745 750Arg Ile Ile Thr Gly Pro Glu Ile Lys Tyr Thr Arg Ile Ser Thr Gly755 760 765Gly Gly Glu Thr Glu Glu Thr Leu Lys Lys Leu Leu Gln Glu Glu Val770 775 780Thr Lys Val Thr Lys Phe Ile Glu Gly Gly Asp Gly His Leu Phe Glu785 790 795 800Asp Glu Glu Ile Lys Arg Leu Leu Gln Gly Asp Thr Pro Val Arg Lys805 810 815Leu Gln Ala Asn Lys Lys Val Gln Gly Ser Arg Arg Arg Leu Arg Glu820 825 830Gly Arg Ser Gln83權利要求
1.一種多層聚合物包裹物，它包括至少兩個可生物降解的聚合物片層，其中，所述至少兩個可生物降解的聚合物片層相互結合，所述多層聚合物包裹物還包含至少一種成骨誘導性制劑。
2.如權利要求1所述的多層聚合物包裹物，其特征在于，所述至少一種成骨誘導性制劑包含在至少一個可生物降解的聚合物片層中。
3.如權利要求1所述的多層聚合物包裹物，其特征在于，所述至少一種成骨誘導性制劑包含在至少兩個可生物降解的聚合物片層之間。
4.如權利要求1所述的多層聚合物包裹物，其特征在于，所述成骨誘導性制劑還包含一種或多種成骨誘導劑。
5.如權利要求4所述的多層聚合物包裹物，其特征在于，所述一種或多種成骨誘導劑包括BMP-2。
6.如權利要求4所述的多層聚合物包裹物，其特征在于，所述一種或多種成骨誘導劑選自BMP-1、BMP-2、BMP-3、BMP-4、BMP-5、BMP-6、BMP-7、BMP-8、BMP-9、BMP-10、BMP-11、BMP-12、BMP-13、BMP-15、BMP-16、BMP-17、BMP-18或其任意組合。
7.如權利要求4所述的多層聚合物包裹物，其特征在于，所述一種或多種成骨誘導劑選自CTGF-1、CTGF-2、CGTF-3、CTGF-4或其任意組合。
8.如權利要求4所述的多層聚合物包裹物，其特征在于，所述一種或多種成骨誘導劑選自VEGF-A、VEGF-B、VEGF-C、VEGF-D、VEGF-E或其任意組合。
9.如權利要求4所述的多層聚合物包裹物，其特征在于，所述一種或多種成骨誘導劑是護骨蛋白。
10.如權利要求4所述的多層聚合物包裹物，其特征在于，所述一種或多種成骨誘導劑選自TGF-β-1、TGF-β-2、TGF-β-3或其任意組合。
11.如權利要求4所述的多層聚合物包裹物，其特征在于，所述一種或多種成骨誘導劑選自一種或多種BMP、一種或多種VEGF、一種或多種CTGF、護骨蛋白、一種或多種TGF-β或其任意組合。
12.如權利要求4所述的多層聚合物包裹物，其特征在于，所述一種或多種成骨誘導劑以治療性多核苷酸的形式提供。
13.如權利要求4所述的多層聚合物包裹物，其特征在于，所述一種或多種成骨誘導劑以治療性多肽的形式提供。
14.如權利要求13所述的多層聚合物包裹物，其特征在于，所述治療性多肽以成熟多肽的形式給予。
15.如權利要求1所述的多層聚合物包裹物，其特征在于，所述成骨誘導性制劑包括緩釋制劑。
16.如權利要求4所述的多層聚合物包裹物，其特征在于，所述成骨誘導性制劑還包含一種或多種抗生素。
17.如權利要求4所述的多層聚合物包裹物，其特征在于，所述成骨誘導性制劑還包含脫礦物質骨基質。
18.如權利要求4所述的多層聚合物包裹物，其特征在于，所述成骨誘導性制劑還包含骨髓抽吸物。
19.如權利要求4所述的多層聚合物包裹物，其特征在于，所述成骨誘導性制劑還包含骨髓濃縮物。
20.如權利要求4所述的多層聚合物包裹物，其特征在于，所述成骨誘導性制劑還包含一種或多種免疫抑制劑。
21.如權利要求4所述的多層聚合物包裹物，其特征在于，所述成骨誘導性制劑還包含載體。
22.如權利要求21所述的多層聚合物包裹物，其特征在于，所述載體是膠原。
23.如權利要求22所述的多層聚合物包裹物，其特征在于，所述膠原是重組產生的膠原。
24.一種成套工具，它包括含有成骨誘導劑的用于植入的多層聚合物包裹物。
25.如權利要求24所述的成套工具，其特征在于，所述多層聚合物包裹物包含成骨誘導性制劑。
26.如權利要求1所述的多層聚合物包裹物，其特征在于，所述至少兩個可生物降解的聚合物片層各自包含含有至少一種成骨誘導劑的至少一種成骨誘導性制劑。
27.如權利要求26所述的多層聚合物包裹物，其特征在于，所述至少兩個可生物降解的聚合物片層在成骨誘導性制劑中包含至少一種不同的成骨誘導劑。
28.如權利要求26所述的多層聚合物包裹物，其特征在于，所述至少兩個可生物降解的聚合物片層在成骨誘導性制劑中包含不同濃度的至少一種成骨誘導劑。
29.一種包含至少一個可生物降解的聚合物片層的聚合物包裹物，其中，所述至少一個可生物降解的聚合物片層還包含至少一種成熟BMP多肽和至少一種成熟護骨蛋白多肽。
30.一種包含至少一個可生物降解的聚合物片層的聚合物包裹物，其中，所述至少一個可生物降解的聚合物片層還包含至少一種編碼成熟BMP多肽的多核苷酸和至少一種編碼成熟護骨蛋白多肽的多核苷酸。
全文摘要
本申請描述了一種包含一種或多種成骨誘導性制劑的聚合物包裹物，其中，所述成骨誘導性制劑各自包含一種或多種成骨誘導劑。在一個實施方式中，成骨誘導性制劑包含在可生物降解的聚合物片層中。在本發(fā)明另一個實施方式中，聚合物包裹物包括至少兩個或多個獨立的可生物降解聚合物片層或層，其任選地包含含有至少一種成骨誘導劑的成骨誘導性制劑。成骨誘導性制劑可以是速釋或緩釋制劑。該方法還涉及預防和治療植入矯形外科裝置或其它植入物后形成的溶骨性病變。
文檔編號A61L27/54GK101068509SQ200580036296
公開日2007年11月7日 申請日期2005年8月31日 優(yōu)先權日2004年9月1日
發(fā)明者J·C·塞爾布賽克 申請人:華沙整形外科股份有限公司