專利名稱：膠原凝集素－補(bǔ)體激活蛋白嵌合體的制作方法
背景技術(shù)：
本發(fā)明涉及能夠激活補(bǔ)體系統(tǒng)的融合蛋白，產(chǎn)生所述融合蛋白的方法以及包含所述融合蛋白的藥物組合物，和用所述融合蛋白治療疾病，特別是感染的方法。
背景技術(shù)：
動(dòng)物已經(jīng)發(fā)展了不同的復(fù)雜策略來(lái)保護(hù)它們對(duì)抗感染。免疫反應(yīng)被分為兩個(gè)主要的組，獲得性免疫反應(yīng)和先天免疫反應(yīng)，前者中出現(xiàn)了適應(yīng)并且細(xì)胞的作用占優(yōu)勢(shì)，后者可即時(shí)享用并且主要基于體液中存在的分子。先天免疫系統(tǒng)在出生時(shí)就可以運(yùn)作(operational)，與此相比獲得性免疫防御只在嬰兒期獲得其保護(hù)機(jī)體的全部能力(Janeway等，1999)。
在粘膜表面或通過(guò)破損皮膚進(jìn)入機(jī)體的細(xì)菌迅速為膠原凝集素(collectin所識(shí)別，所述膠原凝集素是識(shí)別存在于微生物的表面但不在多細(xì)胞生物體細(xì)胞上的獨(dú)特糖構(gòu)型的可溶蛋白家族。因此膠原凝集素屬于先天免疫系統(tǒng)的龐大并且多樣的一組模式識(shí)別受體。人類已知三種膠原凝集素，然而可能存在其它的膠原凝集素，例如牛中就有更多。膠原凝集素靶向粒子，并與粒子結(jié)合，從而被吞噬細(xì)胞攝入或者激活補(bǔ)體級(jí)聯(lián)，通過(guò)這種方式可以介導(dǎo)它們的破壞。
膠原凝集素都顯示如下結(jié)構(gòu)它們有N-末端半胱氨酸富集區(qū)，該區(qū)顯示形成了鏈間二硫鍵，之后是膠原蛋白樣(collagen-like)區(qū)，卷曲螺旋型α-螺旋區(qū)，最后是C-型凝集素結(jié)構(gòu)域，該結(jié)構(gòu)域是模式識(shí)別區(qū)，并且被稱作糖識(shí)別區(qū)(CRD)。膠原凝集素的名字源自膠原蛋白和凝集素結(jié)構(gòu)域的存在。由所述卷曲螺旋型α-螺旋區(qū)啟動(dòng)個(gè)體多肽的三聚化來(lái)形成膠原蛋白三重(triple)螺旋，從而產(chǎn)生膠原凝集素亞基，每個(gè)亞基由三個(gè)個(gè)體多肽組成，而N-末端區(qū)介導(dǎo)亞基寡聚體的形成。不同的膠原凝集素表現(xiàn)出獨(dú)特的高級(jí)結(jié)構(gòu)，通常是亞基四聚體或亞基六聚體。大量結(jié)合區(qū)的分組(grouping)使膠原凝集素以高親合力與微生物細(xì)胞壁結(jié)合，但每個(gè)CRD對(duì)糖的內(nèi)在親合力相對(duì)較低。
在系統(tǒng)發(fā)生和功能方面，C-型CRD廣泛出現(xiàn)在蛋白中。不同膠原凝集素的不同CRD使它們識(shí)別在不同微生物表面出現(xiàn)的一些獨(dú)特的微生物表面組分。末端CRD的分布使存在結(jié)合位點(diǎn)的三個(gè)結(jié)構(gòu)域靶表面都有約53的間距(spacing)(Sheriff等，1994；Weis & Drickamer，1994)。此“模式識(shí)別”性質(zhì)可進(jìn)一步造成選擇性結(jié)合微生物表面。膠原凝集素的膠原蛋白區(qū)或可能是N-末端尾部被吞噬細(xì)胞上的特異性受體識(shí)別，因此它是相關(guān)蛋白酶的結(jié)合位點(diǎn)，這些蛋白酶在所述CRD區(qū)結(jié)合了靶之后被激活以啟動(dòng)補(bǔ)體級(jí)聯(lián)。
結(jié)合甘露聚糖的凝集素(MBL)也被稱作結(jié)合甘露糖的凝集素或甘露糖結(jié)合蛋白，作為先天免疫系統(tǒng)的重要部分，它是一種引起重視的膠原凝集素。MBL結(jié)合細(xì)菌、酵母、寄生的原生動(dòng)物和病毒等在很多微生物表面發(fā)現(xiàn)的特異性糖結(jié)構(gòu)，它也通過(guò)激活末端水解性補(bǔ)體組分來(lái)介導(dǎo)殺傷或通過(guò)促進(jìn)吞噬作用來(lái)表現(xiàn)抗細(xì)菌活性。MBL缺陷與兒童，可能還有成人頻繁感染多種微生物的易感性有關(guān)。
MBL的CRD優(yōu)先識(shí)別帶有平展的(equatorial)3-和4-OH基團(tuán)的己糖，如甘露糖，葡萄糖，N-乙酰甘露糖胺和N-乙酰葡萄糖胺，但是不結(jié)合不符合此立體需要的糖，如半乳糖和D-巖藻糖(Weis等，1992)。所述糖選擇性明顯是MBL分辨自身/非自身的重要方面，并且可能被甘露糖和N-乙酰葡萄糖胺殘基在微生物表面的優(yōu)勢(shì)(prevalence)差別來(lái)介導(dǎo)，一個(gè)例子是甘露糖在酵母細(xì)胞壁上的高含量，所述酵母如釀酒酵母(Saccharomyces cererisiae)和白色念珠菌(Candida albicans)。哺乳動(dòng)物蛋白糖基化中的糖結(jié)構(gòu)通常通過(guò)唾液酸來(lái)補(bǔ)充(completed)，其避免了MBL和這些寡聚糖結(jié)合，從而避免了MBL識(shí)別“自身”表面。此外，每個(gè)MBL亞基的三聚體結(jié)構(gòu)可能對(duì)于識(shí)別靶是重要的。
補(bǔ)體是一組存在于血漿和組織液中的蛋白，它輔助機(jī)體在感染后的防御。所述補(bǔ)體系統(tǒng)通過(guò)至少三種不同途徑被激活，其分別被稱為經(jīng)典途徑，替代途徑，和MBLectin途徑(Janeway等，1999)。當(dāng)補(bǔ)體因子1(C1)識(shí)別表面結(jié)合的免疫球蛋白時(shí)，所述經(jīng)典途徑被啟動(dòng)。C1復(fù)合體由兩種蛋白水解酶C1r和C1s，和包括免疫球蛋白識(shí)別區(qū)的非酶部分C1q組成。C1q和MBL共享結(jié)構(gòu)特征，兩種分子在電子顯微鏡下都可見(jiàn)到具有花束樣外型(appearance)。同樣，象C1q一樣，MBL被發(fā)現(xiàn)與兩種蛋白水解酶，結(jié)合甘露聚糖的凝集素相關(guān)的蛋白酶(MASP)復(fù)合。所述三種途徑均產(chǎn)生補(bǔ)體因子3(C3)轉(zhuǎn)化酶，它確保C3b結(jié)合到激活表面的表面，即被靶向的微生物病原體。將C3轉(zhuǎn)化為表面結(jié)合的C3b在通過(guò)吞噬作用或水解作用去除微生物病原體的過(guò)程中是關(guān)鍵的(Janeway等，1999)。
已經(jīng)報(bào)道沙門氏菌的某些O-抗原特異性寡糖會(huì)激活C4-缺陷型豚鼠血清中的補(bǔ)體，然后沙門血清型C顯示與MBL反應(yīng)從而通過(guò)MBLlectin途徑激活補(bǔ)體，它也被稱為補(bǔ)體激活的MBL途徑或凝集素途徑。
一段時(shí)間以來(lái)猜測(cè)在產(chǎn)生特異性免疫反應(yīng)時(shí)，先天免疫系統(tǒng)可能與獲得性免疫系統(tǒng)協(xié)作，例如感染或免疫接種后的抗體反應(yīng)。Fearon小組已經(jīng)顯示用基因技術(shù)通過(guò)融合使補(bǔ)體因子C3的C3d片段與蛋白抗原結(jié)合可將所述抗原的免疫原性提高1000倍或更多。此技術(shù)或其任何改良技術(shù)的實(shí)際應(yīng)用仍有待時(shí)日。
補(bǔ)體系統(tǒng)對(duì)于正常免疫反應(yīng)的重要性首先由Pepys提出，他發(fā)現(xiàn)用眼鏡蛇蛇毒因子耗盡小鼠的C3后該小鼠對(duì)羊紅細(xì)胞、一種胸腺依賴性抗原的抗體反應(yīng)受損。在C4，C2和C3缺乏的病人和實(shí)驗(yàn)動(dòng)物中，對(duì)于胸腺依賴性抗原的初次抗體反應(yīng)減弱和IgM向IgG轉(zhuǎn)換受損，這些報(bào)道支持先天免疫和獲得性免疫是有聯(lián)系的觀點(diǎn)。此機(jī)制可能涉及產(chǎn)生C3衍生的配體，它使抗原或包含抗原的復(fù)合體與抗原呈遞細(xì)胞或B細(xì)胞上的補(bǔ)體受體結(jié)合。因此，用特異性抗CR1和抗CR2的抗體或用水溶性受體蛋白阻斷小鼠的CR1(CD35)和CR2(CD21)會(huì)減少對(duì)免疫接種的抗體反應(yīng)，并且使用CR1和CR2缺陷的敲除小鼠的實(shí)驗(yàn)顯示在對(duì)胸腺依賴性抗原的反應(yīng)中需要這些受體。另外，有白細(xì)胞粘附缺陷、缺乏CD11/CD18粘附分子CR3的病人表現(xiàn)出抗體反應(yīng)受損并且不能將IgM轉(zhuǎn)換為IgG。如上所述，C3衍生的片段C3d是一種特異性CR2配體，它表現(xiàn)出強(qiáng)的劑量依賴性佐劑作用。
經(jīng)典補(bǔ)體途徑(C1，C2，C4和C3)的缺陷與被包裹的細(xì)菌的感染有關(guān)。它主要的原因可能是由于補(bǔ)體功能異常導(dǎo)致的調(diào)理和殺細(xì)菌防御機(jī)制有效性下降。然而，也可考慮對(duì)多糖抗原受損的免疫反應(yīng)。未深入研究補(bǔ)體對(duì)胸腺非依賴性抗原的反應(yīng)的影響，現(xiàn)有信息是矛盾的。因此，根據(jù)文獻(xiàn)記載，C3-耗盡的小鼠和C3-缺陷的狗對(duì)胸腺非依賴性抗原的抗體反應(yīng)是低的。而另一些報(bào)道發(fā)現(xiàn)，C3-缺陷的病人對(duì)用多糖疫苗免疫接種的反應(yīng)看來(lái)是正常的。
Ficolins，象MBL一樣，是包括膠原蛋白樣區(qū)的凝集素。然而，與MBL不同，它們有纖維蛋白原樣區(qū)，它類似纖維蛋白原的β-和γ-鏈。Ficolins也形成結(jié)構(gòu)亞基的寡聚體，每個(gè)由三個(gè)相同的35kDa多肽組成。每個(gè)亞基由氨基末端，半胱氨酸富集區(qū)；膠原蛋白樣區(qū)，其由Gly-Xaa-Yaa三聯(lián)體序列的串聯(lián)重復(fù)組成(其中Xaa和Yaa表示任何氨基酸)；頸區(qū)；和纖維蛋白原樣區(qū)組成。Ficolin的寡聚體包含兩個(gè)或更多個(gè)亞基，特別是已經(jīng)觀察到ficolin的四聚體形式。
一些ficolin以與MBL基本相同的方式引發(fā)了補(bǔ)體系統(tǒng)的活化。對(duì)補(bǔ)體系統(tǒng)的這種引發(fā)導(dǎo)致如上所述的新的絲氨酸蛋白酶(MASPs)的活化。
多種凝集素的纖維蛋白原樣區(qū)與C-型凝集素包括MBL的CRD具有相同的功能，因此它們象模式識(shí)別受體一樣辨別病原體和自身。
血清ficolin對(duì)GlcNAc(N-乙酰葡萄糖胺)，彈性蛋白或GalNAc(N-乙酰半乳糖胺)有共同的結(jié)合特異性。所述纖維蛋白原樣區(qū)負(fù)責(zé)結(jié)合糖。在人的血清中已經(jīng)鑒定了兩種ficolin，L-ficolin(P35，ficolin L，ficolin 2或hucolin)和H-ficolin(Hakata抗原，ficolin 3或不耐熱的b2-巨糖蛋白)，并且兩種都有凝集素活性。L-ficolin識(shí)別GlcNAc，H-ficolin識(shí)別GalNAc。另一種已知是M-ficolin的ficolin(P35相關(guān)性蛋白，F(xiàn)icolin 1或Ficolin A)被認(rèn)為不是血清蛋白，它可見(jiàn)于白細(xì)胞和肺。L-ficolin和H-ficolin激活了與MASPs相關(guān)的凝集素補(bǔ)體途徑。M-ficolin，L-ficolin和H-ficolin有鈣非依賴性凝集素活性。
MASP(MBL相關(guān)性絲氨酸蛋白酶)包含MASP-1，MASP-2和MASP-3，它們是負(fù)責(zé)激活凝集素途徑的蛋白水解酶。MASP的總體結(jié)構(gòu)類似經(jīng)典補(bǔ)體途徑中第一種因子的兩種蛋白水解組分，C1r和C1s的結(jié)構(gòu)。當(dāng)MBL或與MASP-1，MASP-2，MASP-3和sMAP相關(guān)的ficolin結(jié)合例如細(xì)菌、酵母、寄生的原生動(dòng)物、病毒的表面的糖結(jié)構(gòu)時(shí)，啟動(dòng)了凝集素途徑。MASP-2是酶組分，它類似經(jīng)典途徑中的C1s，可切斷補(bǔ)體組分C4和C2來(lái)形成C3轉(zhuǎn)化酶C4bC2a，此酶對(duì)于凝集素-和經(jīng)典-激活途徑都是共同的。
MASP-1，MASP-2，MASP-3和sMAP由兩個(gè)基因編碼；sMAP是MASP-2的截?cái)嗟男问?，并且MASP-3是由MASP-1基因通過(guò)可變剪接產(chǎn)生的。MASP-1基因有MASP-1和MASP-3共有的H-鏈編碼區(qū)，其后是對(duì)MASP-1和MASP-3特異的蛋白酶區(qū)編碼區(qū)的串聯(lián)重復(fù)。
MASP家族可分為兩個(gè)系統(tǒng)發(fā)生的譜系，TCN型和AGY型譜系。TCN型譜系包括MASP-1，它有編碼活性位點(diǎn)絲氨酸的TCN密碼子(其中N表示A，G，C或T)，存在組氨酸-環(huán)二硫鍵和分隔(split)的多個(gè)外顯子。與此相比，AGY型譜系包括MASP-2，MASP-3，C1r和C1s，其特征為編碼活性位點(diǎn)絲氨酸的AGY密碼子(其中Y表示C或T)，不存在組氨酸-環(huán)和單一外顯子。
MASP-1，MASP-2，MASP-3，C1r和C1s由六個(gè)區(qū)組成兩個(gè)C1r/C1s/Uegf/骨形態(tài)發(fā)生蛋白1(CUB)區(qū)；一個(gè)表皮生長(zhǎng)因子(EGF)樣區(qū)；兩個(gè)補(bǔ)體控制蛋白(CCP)區(qū)或短共有序列重復(fù)(SCRs)，和絲氨酸蛋白酶區(qū)。組氨酸(H)，天冬氨酸(D)和絲氨酸(S)殘基是在絲氨酸蛋白酶區(qū)中形成活性中心所必需的。只有MASP-1在輕鏈中有兩個(gè)另外的半胱氨酸殘基，它們形成組氨酸環(huán)二硫鍵(S-S)，如胰蛋白酶和胰凝乳蛋白酶中所見(jiàn)。在MBL和ficolin結(jié)合到病原體表面上的糖后，MASP的酶原形式在第二個(gè)CCP和蛋白酶區(qū)之間裂解，從而得到活性形式，其由兩個(gè)多肽，重鏈和輕鏈組成(也稱為A和B鏈)。
發(fā)明概述本發(fā)明涉及能夠激活補(bǔ)體系統(tǒng)的融合蛋白。因此，本發(fā)明涉及一種融合蛋白，包含源自凝集素-補(bǔ)體途徑激活蛋白(補(bǔ)體激活蛋白)或其功能同系物的第一多肽序列；和源自膠原凝集素或其功能同系物的第二多肽序列；其中所述補(bǔ)體激活蛋白不是膠原凝集素。
所述融合蛋白適用于治療，包括產(chǎn)生，重建，增強(qiáng)和/或刺激補(bǔ)體系統(tǒng)的調(diào)理和/或殺細(xì)菌活性，即增強(qiáng)免疫防御識(shí)別并殺死微生物病原體的能力。因此，本發(fā)明涉及包含所述融合蛋白的藥物。
本發(fā)明另一方面也涉及對(duì)有需要的個(gè)體治療臨床狀況的方法，其包括給藥所述個(gè)體如上限的融合蛋白。
本發(fā)明另一方面涉及治療或預(yù)防有需要的個(gè)體的臨床狀況，如感染的方法，其包括對(duì)所述個(gè)體給藥融合蛋白，其包含源自能夠形成結(jié)構(gòu)單元的寡聚體的蛋白的第一多肽序列；和源自結(jié)合甘露糖的凝集素(MBL)的第二多肽序列，其中所述第一多肽序列和所述第二肽序列不源自相同的蛋白，并且所述融合蛋白能夠與甘露糖相關(guān)性絲氨酸蛋白酶(MASP)相連。所述第一多肽序列優(yōu)選源自能夠形成結(jié)構(gòu)單元的四聚體、五聚體、和/或六聚體的蛋白。在優(yōu)選實(shí)施方案中，所述第一多肽序列和所述第二多肽序列如下所述。
本發(fā)明還涉及如上述的融合蛋白在制備用于治療有需要的個(gè)體的臨床狀況的藥物中的用途。
本發(fā)明還涉及制備所述融合蛋白的方法，以及編碼所述融合蛋白的分離的核酸序列，包含所述序列的載體以及包含所述載體的細(xì)胞。
附圖簡(jiǎn)述

圖1顯示L-ficolin的序列。
圖2顯示MBL的序列。
圖3顯示融合蛋白的例子。
圖4-8顯示了實(shí)施例1所述的質(zhì)粒。
圖9顯示實(shí)施例1所述的融合蛋白的比對(duì)。
圖10顯示實(shí)施例2所討論的兩個(gè)Western印跡。
定義膠原凝集素先天免疫力中結(jié)構(gòu)上相關(guān)的、識(shí)別糖的一族蛋白，其包括結(jié)合甘露聚糖的凝集素(MBL)和表面活性蛋白A和D。該名字指存在有膠原蛋白樣區(qū)和C-型凝集素區(qū)。
補(bǔ)體一組存在于血漿和組織液中、在感染后輔助機(jī)體防御的蛋白。補(bǔ)體參與破壞異源細(xì)胞并將吞噬細(xì)胞吸引到機(jī)體中的沖突(conflict)區(qū)域。
偶聯(lián)的在兩種化合物，例如免疫原性決定簇和膠原凝集素和/或膠原凝集素同系物之間，或者免疫原性決定簇和糖之間形成的連接。該連接可能是通過(guò)例如形成化學(xué)鍵如共價(jià)鍵而產(chǎn)生的物理連接。
CRD糖識(shí)別區(qū)，發(fā)現(xiàn)于膠原凝集素C-末端的C-型凝集素區(qū)。
免疫原性決定簇分子或其部分，其包含刺激宿主生物體的免疫系統(tǒng)產(chǎn)生抗原特異性分泌型體液反應(yīng)和/或細(xì)胞反應(yīng)的一或多個(gè)表位，或者能夠在脊椎動(dòng)物產(chǎn)生此類免疫原的DNA分子。
免疫反應(yīng)對(duì)包含免疫原性決定簇的免疫原性組合物的反應(yīng)。免疫反應(yīng)包括在宿主中產(chǎn)生的對(duì)于所給予的目標(biāo)組合物或疫苗的細(xì)胞和/或體液免疫反應(yīng)。免疫反應(yīng)通常包括特異性或非特異性針對(duì)在所給予的免疫原性組合物中存在的免疫原性決定簇的i)產(chǎn)生的抗體，ii)B細(xì)胞，iii)輔助性T細(xì)胞，iv)抑制性T細(xì)胞，v)細(xì)胞毒性T細(xì)胞，和vi)補(bǔ)體中一或多個(gè)的作用。
凝集素特異性結(jié)合糖的蛋白。
MASP甘露糖相關(guān)性絲氨酸蛋白酶。
MBL結(jié)合甘露聚糖的凝集素或結(jié)合甘露糖的凝集素。
亞基復(fù)合體＝結(jié)構(gòu)單元三個(gè)融合蛋白的復(fù)合體，其類似如上討論MBL和ficolin時(shí)的亞基復(fù)合體。

發(fā)明內(nèi)容
本發(fā)明目的是提供能夠激活補(bǔ)體系統(tǒng)的融合蛋白，來(lái)輔助預(yù)防或治療疾病，特別是感染性疾病。
所述融合蛋白由源自凝集素補(bǔ)體途徑激活蛋白(＝補(bǔ)體激活蛋白)或其功能同系物的第一多肽序列；和源自膠原凝集素或其功能同系物的第二多肽序列組成；其中所述補(bǔ)體激活蛋白不是膠原凝集素。
通過(guò)將源自凝集素補(bǔ)體途徑激活蛋白的多肽序列和源自膠原凝集素的多肽序列組合，可以設(shè)計(jì)出對(duì)多種糖，優(yōu)選細(xì)菌和病毒的糖有結(jié)合親合力同時(shí)具有補(bǔ)體系統(tǒng)激活活性的融合蛋白。
第一多肽序列所述第一多肽序列可以源自任何凝集素補(bǔ)體途徑激活蛋白。所述凝集素補(bǔ)體途徑激活蛋白可以是天然出現(xiàn)的凝集素補(bǔ)體途徑激活蛋白以及所述凝集素補(bǔ)體途徑激活蛋白的變體或同系物，其中所述變體或同系物保持了凝集素補(bǔ)體途徑激活的活性。
優(yōu)選所述融合蛋白能夠形成亞基復(fù)合體，每個(gè)復(fù)合體由三個(gè)如上所限定的融合蛋白組成。
所述第一多肽序列也優(yōu)選能夠與另一融合蛋白的第一多肽序列形成寡聚復(fù)合體，其中所述另一融合蛋白可以與第一種融合蛋白相同。因此可提供兩個(gè)或更多融合蛋白或兩個(gè)或更多亞基復(fù)合體的寡聚復(fù)合體，所述寡聚復(fù)合體比單體融合蛋白對(duì)細(xì)菌或病毒的糖的結(jié)合親合力高。在優(yōu)選實(shí)施方案中，所述寡聚的復(fù)合體是二聚的亞基復(fù)合體，更優(yōu)選是三聚的亞基復(fù)合體，再更優(yōu)選是四聚的亞基復(fù)合體。
在優(yōu)選實(shí)施方案中，所述凝集素補(bǔ)體途徑激活蛋白是如上所限的ficolin。所述ficolin可以是L-ficolin，H-ficolin或M-ficolin或其變體或同系物。在優(yōu)選實(shí)施方案中，所述凝集素補(bǔ)體途徑激活蛋白是L-ficolin。
另一實(shí)施方案中所述第一多肽序列包含所述凝集素的纖維蛋白原區(qū)，和/或凝集素的頸區(qū)，如ficolin或其變體或同系物。
當(dāng)所述第一多肽序列衍生自ficolin或ficolin的變體或同系物時(shí)，優(yōu)選所述第一多肽序列包含來(lái)自ficolin或ficolin的變體或同系物的膠原蛋白樣區(qū)。另一實(shí)施方案中優(yōu)選所述第一多肽序列包含來(lái)自ficolin或ficolin的變體或同系物的半胱氨酸富集區(qū)。甚更優(yōu)選所述第一多肽序列包含來(lái)自ficolin或ficolin的變體或同系物的膠原蛋白樣區(qū)和半胱氨酸富集區(qū)。
更優(yōu)選所述第一多肽序列包含來(lái)自L-ficolin或L-ficolin的變體或同系物的膠原蛋白樣區(qū)。另一實(shí)施方案中更優(yōu)選所述第一多肽序列包含來(lái)自L-ficolin或L-ficolin的變體或同系物的半胱氨酸富集區(qū)。甚更優(yōu)選所述第一多肽序列包含L-ficolin的N-末端區(qū)，其包括兩個(gè)半胱氨酸氨基酸殘基。
甚更優(yōu)選所述第一多肽序列包含來(lái)自L-ficolin或L-ficolin的變體或同系物的膠原蛋白樣區(qū)和半胱氨酸富集區(qū)。
在特別優(yōu)選的實(shí)施方案中所述ficolin具有參照序列數(shù)據(jù)庫(kù)和登錄號(hào)如下所列的序列之一。這里描述了每一個(gè)序列的半胱氨酸富集區(qū)和膠原蛋白樣區(qū)。NP_003656.ficolin 3 precursor；ficolin(collagen/fibrinogen domain-containing)3(Hakataantigen)[Homo sapiens][gi:4504331]90..299/region_name＝″pfam00147，fibrinogen_C，F(xiàn)ibrinogen beta and gamma chains，C-terminal globular domain″90..299/region_name＝″smart00186，F(xiàn)BG，F(xiàn)ibrinogen-related domains(FReDs)；Domainpresent at the C-termini of fibrinogen beta and gamma chains，and a variety offibrinogen-related proteins，including tenascin and Drosophila scabrous″1 mdllwilpsl wllllggpac lktqehpscp gpreleaskv vllpscpgap gspgekgapg61 pqgppgppgk mgpkgepgdp vnllrcqegp rncrellsqg atlsgwyhlc lpegralpvf121 cdmdtegggw lvfqrrqdgs vdffrswssy ragfgnqese fwlgnenlhq ltlqgnwelr181 veledfngnr tfahyatfrl lgevdhyqla lgkfsegtag dslslhsgrp fttydadhds241 snsncavivh gawwyascyr snlngryavs daaahkygid wasgrgvghp yrrvrmmlrXP_116792.similar to Ficolin 2 precursor(Collagen/fibrinogen domain-containing protein 2)(Ficolin-B)(Ficolin B)(Serum lectin P35)(EBP-37)(Hucolin)(L-Ficolin)[Homo sapiens][gi:20477458]91..168/region_name＝″pfam00147，fibrinogen_C，F(xiàn)ibrinogen beta and gamma chains，C-terminal globular domain″91..168/region_name＝″smart00186，F(xiàn)BG，F(xiàn)ibrinogen-related domains(FReDs)；Domainpresent at the C-termini of fibrinogen beta and gamma chains，and a variety offibrinogen-related proteins，including tenascin and Drosophila scabrous″
1 mgpallalsf lwtmaltedt cpamleyval nsepgmaskn psrrhglsll vvdqgpgarg61 vrtdqgpsga dpgslelhge cpifpseqvi lthhnnypfs tedqdndrda encavhyqga121 wwyaschlsh lngvylggar dsftnginwk sgkgnnysyk vsemkvrptO00602.Ficolin 1 precursor(Collagen/fibrinogen domain-containing protein 1)(Ficolin-A)(Ficolin A)(M-Ficolin)[gi:20455484]1..29/gene＝″FCN1″/region_name＝″Signal″/note＝″POTENTIAL.″30..326/gene＝″FCN1″/region_name＝″Mature chain″/note＝″FICOLIN 1.″55..93/gene＝″FCN1″/region_name＝″Domain″/note＝″COLLAGEN-LIKE.″133/gene＝″FCN1″/region_name＝″Conflict″/note＝″T-＞N(IN REF.1).″144..290/gene＝″FCN1″/region_name＝″Domain″/note＝″FIBRINOGEN C-TERMINAL.″287/gene＝″FCN1″/region_name＝″Conflict″/note＝″N-＞S(IN REF.1).″305/gene＝″FCN1″/site_type＝″glycosylation″/note＝″N-LINKED(GLCNAC...)(POTENTIAL).″1 melsgatma rglavllvlfl hiknlpaqaa dtcpevkvvg legsdkltil rgcpglpgap61 gpkgeagvig ergerglpga pgkagpvgpk gdrgekgmrg ekgdagqsqs catgprnckd121 lldrgyflsg whtiylpdcr pltvlcdmdt dgggwtvfqr rmdgsvdfyr dwaaykqgfg181 sqlgefwlgn dnihaltaqg sselrvdlvd fegnhqfaky ksfkvadeae kyklvlgafv241 ggsagnsltg hnnnffstkd qdndvsssnc aekfqgawwy adchasnlng lylmgphesy301 anginwsaak gykysykvse mkvrpa//O75636.Ficolin 3 precursor(Collagen/fibrinogen domain-containing protein 3)(Collagen/fibrinogen domain-containing lectin 3 P35)(Hakata antigen)[gi:13124185]1..21/gene＝″FCN3″/region_name＝″Signal″/note＝″POTENTIAL.″22..299/gene＝″FCN3″/region_name＝″Mature chain″/note＝″FICOLIN 3.″48..80/gene＝″FCN3″/region_name＝″Domain″/note＝″COLLAGEN-LIKE.″50/gene＝″FCN3″/site_type＝″hydroxylation″53/gene＝″FCN3″/site_type＝″hydroxylation″59/gene＝″FCN3″/site_type＝″hydroxylation″65/gene＝″FCN3″/site_type＝″hydroxylation″68/gene＝″FCN3″/site_type＝″hydroxylation″77/gene＝″FCN3″/site_type＝″hydroxylation″119..265/gene＝″FCN3″/region_name＝″Domain″/note＝″FIBRINOGEN C-TERMINAL.″189/gene＝″FCN3″/sife_type＝″glycosylation″/note＝″N-LINKED(GLCNAC...)(POTENTIAL).″1 mdllwilpsl wllllggpac lktqehpscp gpreleaskv vllpscpgap gspgekgapg61 pqgppgppgk mgpkgepgdp vnllrcqegp rncrellsqg atlsgwyhlc lpegralpvf121 cdmdtegggw lvfqrrqdgs vdffrswssy ragfgnqese fwlgnenlhq ltlqgnwelr181 veledfngnr tfahyatfrk lgevdhyqla lgkfsegtag dslslhsgrp fttydadhds241 snsncavivh gawwyascyr snlngryavs daaahkygid wasgrgvghp yrrvrmmlrXP_130120.similar to Ficolin 2 precursor(Collagen/fibrinogen domain-containing protein 2)(Ficolin-B)(Ficolin B)(Serum lectin P35)(EBP-37)(Hucolin)[Mus musculus][gi:20823464]59..95/region_name＝″Collagen triple helix repeat(20copies)″/note＝″Collagen″/db_xref＝″CDD:pfam01391″59..89/region_name＝″Collagen triple helix repeat(20copies)″/note＝″Collagen″/db_xref＝″CDD:pfam01391″60..95/region_name＝″Collagen triple helix repeat(20copies)″/note＝″Collagen″/db_xref＝″CDD:pfam01391″60..95/region_name＝″Collagen triple helix repeat(20copies)″/note＝″Collagen″/db_xref＝″CDD:pfam01391″60..95/region_name＝″Collagen triple helix repeat(20copies)″/note＝″Collagen″/db_xref＝″CDD:pfam01391″60..95/region_name＝″Collagen triple helix repeat(20copies)″/note＝″Collagen″/db_xref＝″CDD:pfam01391″60..95/region_name＝″Collagen triple helix repeat(20copies)″/note＝″Collagen″/db_xref＝″CDD:pfam01391″61..95/region_name＝″Collagan triple helix repeat(20copies)″/note＝″Collageh″/db_xref＝″CDD:pfam01391″61..95/region_name＝″Collagen triple helix repeat(20copies)″/note＝″Collagen″/db_xref＝″CDD:pfam01391″61..95/region_name＝″Collagen triple helix repeat(20copies)″/note＝″Collagen″/db_xref＝″CDD:pfam01391″103..312/region_name＝″Fibrinogen beta and gamma chains，C-terminal globulardomain″/note＝″fibrinogen_C″/db_xref＝″CDD:pfam00147″103..312/region_name＝″Fibrinogen-related domains(FReDs)″/note＝″FBG″/db_xref＝″CDD:smart00186″1 malgsaalfv ltltvhaagt cpelkvldle gykqltilqg cpglpgaagp kgeagakgdr61 gesglpgipg kegptgpkgn qgekgirgek gdsgpsqsca tgprtckell tqghfltgwy121 tiylpdcrpl tvlcdmdtdg ggwtvfqrrl dgsvdffrdw tsykrgfgsq lgefwlgndn181 ihalttqgts elrvdlsdfe gkhdfakyss fqiqgeaeky klilgnflgg gagdsltphn241 nrlfstkdqd ndgstsscam gyhgawwysq chtsnlngly lrgphksyan gvnwkswrgy301 nysckvsemk vrliNP_056654.ficolin 2 isoform d precursor；ficolin(collagen/fibrinogen domain-containing lectin)2(hucolin)；ficolin(collagen/fibrinogen domain-containing lectin)2；hucolin[Homo sapiens][gi:8051590]39..95/region_name＝″collagen-like domain″1 meldravgvl gaatlllsfl gmawalqaad tcpevkmvgl egsdkltilr gcpglpgapg61 dkgeagtngk rgergppgpp gkagppgpng apgepqpclt gdNP_056653.ficoli 2 isoform c precursor；ficolin(collagen/fibrinogen domain-containing lectin)2(hucolin)；ficolin(collagen/fibrinogen domain-containing lectin)2；hucolin[Homo sapiens][gi:8051588]39..95/region_name＝″collagen-like domain″102..143/region_name＝″Fibrinogen beta and gamma chains，C-terminal globulardomain″/note＝″fibrinogen_C″/db_xref＝″CDD:pfam00147″102..143/region_name＝″Fibrinogen-related domains(FReDs)″/note＝″FBG″/db_xref＝″CDD:smart00186″1 meldraygvl gaatlllsfl gmawalqaad tcpevkmvgl egsdkltilr gcpglpgapg61 dkgeagtngk rgergppgpp gkagppgpng apgepqpclt gprtckdlld rghflsgwht121 iylpdcrplt vlcdmdtdgg gwtvsvglgr ggqpgspggq aahlvgehtl efsillvgds181 qrNP_056652.ficolin 2 isoform b precursor；ficolin(collagen/fibrinogen domain-containing lectin)2(hucolin)；ficolin(collagen/fibrinogen domain-containing lectin)2；hucolin[Homo sapiens][gi:8051586]sig peptide1..25mat peptide26..27560..275/region_name＝″FBG domain″/note＝″fibrinogen beta/gamma homology″64..275/region_name＝″Fibrinogen-related domains(FReDs)″/note＝″FBG″/db_xref＝″CDD:smart00186″64..274/region_name＝″Fibrinogen beta and gamma chains，C-terminal globulardomain″/note＝″fibrinogen_C″/db_xref＝″CDD:pfam00147″
1 meldravgvl gaatlllsfl gmawalqaad tcpgergppg ppgkagppgp ngapgepqpc61 ltgprtckdl ldrghflsgw htiylpdcrp ltvlcdmdtd gggwtvfqrr vdgsvdfyrd121 watykqgfgs rlgefwlgnd nihaltaqgt selrvdlvdf ednyqfakyr sfkvadeaek181 ynlvlgafve gsagdsltfh nnqsfstkdq dndlntgnca vmfqgawwyk nchvsnlngr241 ylrgthgsfa nginwksgkg ynysykvsem kvrpaNP_001994.ficolin 1 precursor；ficolin(collagen/fibrinogen domain-containing)1[Homosapiens][gi:8051584]sig peptide1..27mat peptide28..32640..108/region_name＝″collagen-like domain″50..105/region_name＝″Collagen triple helix repeat(20copies)″/note＝″Collagen″/db_xref＝″CDD:pfam01391″51..107/region_name＝″Collagen triple helix repeat(20copies)″/note＝″Collagen″/db_xref＝″CDD:pfam01391″52..106/region_name＝″Collagen triple helixrepeat(20copies)″/note＝″Collagen″/db_xref＝″CDD:pfam01391″115..326/region_name＝″FBG domain″/note＝″fibrinogen beta/gamma homology″115..326/region_name＝″Fibrinogen-related domains(FReDs)″/note＝″FBG″/db_xref＝″CDD:smart00186″115..325/region_name＝″Fibrinogen beta and gamma chains，C-terminal globulardomain″/note＝″fibrinogen_C″/db_xref＝″CDD:pfam00147″variation315/db_xref＝″dbSNP:1128428″variation316/db_xref＝″dbSNP:1128429″variation317/db_xref＝″dbSNP:1128430″1 melsgatmar glavllvlfl hiknlpaqaa dtcpevkvvg legsdkltil rgcpglpgap61 gpkgeagvig ergerglpga pgkagpvgpk gdrgekgmrg ekgdagqsqs catgprnckd121 lldrgyflsg whtiylpdcr pltvlcdmdt dgggwtvfqr rmdgsvdfyr dwaaykqgfg181 sqlgefwlgn dnihaltaqg sselrvdlvd fegnhqfaky ksfkvadsas kyklvlgafv241 ggsagnsltg hnnnffstkd qdndvsssnc aekfqgawwy adchasnlng lylmgphesy301 anginwsaak gykysykvse mkvrpaNP_004099.ficolin 2 isoform a precursor；ficolin(collagen/fibrinogen domain-containing lectin)2(hucolin)；ficolin(collagen/fibrinogen domain-containing lectin)2；hucolin[Homo sapiens][gi:4758348]sig peptide1..25mat peptide26..31339..95/region_name＝″collagen-like domain″98..313/region_name＝″FBG domain″/note＝″fibrinogen beta/gamma homology″102..313/region_name＝″Fibrinogen-related domains(FReDs)″/note＝″FBG″/db_xref＝″CDD:smart00186″102..312/region_name＝″Fibrinogen beta and gamma chains，C-terminal globulardomain″/note＝″fibrinogen_C″/db_xref＝″CDD:pfam001471 meldravgvl gaatlllsfl gmawalqaad tcpevkmvgl egsdkltilr gcpglpgapg61 dkgeagtngk rgergppgpp gkagppgpng apgepqpclt gprtckdlld rghflsgwht121 iylpdcrplt vlcdmdtdgg gwtvfqrrvd gsvdfyrdwa tykqgfgsrl gefwlgndni181 haltaqgtse lrvdlvdfed nyqfakyrsf kvadeaekyn lvlgafvegs agdsltfhnn241 qsfstkdqdn dlntgncavm fqgawwyknc hvsnlngryl rgthgsfang inwksgkgyn301 ysykvsemkv rpaQ9WTS8.Ficolin 1 precursor(Collagen/fibrinogen domain-containing protein 1)(Ficolin-A)(Ficolin A)(M-Ficolin)[gi:13124116]1..22/gene＝″FCN1″/region_name＝″Signal″/note＝″POTENTIAL.″23..335/gene＝″FCN1″/region_name＝″Mature chain″/note＝″FICOLIN 1.″50..88/gene＝″FCN1″/region_name＝″Domain″/note＝″COLLAGEN-LIKE.″152..298/gene＝″FCN1″/region_name＝″Domain″/note＝″FIBRINOGEN C-TERMINAL.″271/gene＝″FCN1″/site_type＝″glycosylation″/note＝″N-LINKED(GLCNAC...)(POTENTIAL).″1 mwwpmlwafp vllclcssqa lgqesgacpd vkivglgaqd kvaviqscps fpgppgpkge61 pgspagrger glqgspgkmg ppgskgepgt mgppgvkgek gergtasplg qkelgdalcr121 rgprsckdll trgifltgwy tiylpdcrpl tvlcdmdvdg ggwtvfqrrv dgsinfyrdw181 dsykrgfgnl gtefwlgndy lhlltangnq elrvdlrefq gqtsfakyss fqvsgeqeky241 kltlgqfleg tagdsltkhn nmafsthdqd ndtnggknca alfhgawwyh dchqsnlngr301 ylpgshesya dginwlsgrg hrysykvaem kirasQ15485.Ficolin 2 precursor(Collagen/fibrinogen domain-containing protein 2)(Ficolin-B)(Ficolin B)(Serum lectin P35)(EBP-37)(Hucolin)(L-Ficolin)[gi:13124203]1..25/gene＝″FCN2″/region_name＝″Signal″/note＝″POTENTIAL.″26..313/gene＝″FCN2″/region_name＝″Mature chain″/note＝″FICOLIN 2.″54..92/gene＝″FCN2″/region_name＝″Domain″/note＝″COLLAGEN-LIKE.″131..277/gene＝″FCN2″/region_name＝″Domain″/note＝″FIBRINOGEN C-TERMINAL.″240/gene＝″FCN2″/site_type＝″glycosylation″/note＝″N-LINKED(GLCNAC...)(POTENTIAL).″300/gene＝″FCN2″/site_type＝″glycosylation″/note＝″N-LINKED(GLCNAC...)(POTENTIAL).″1 meldravgvl gaatlllsfl gmawalqaad tcpevkmvgl egsdkltilr gcpglpgapg61 dkgeagtngk rgergppgpp gkagppgpng apgepqpclt gprtckdlld rghflsgwht121 iylpdcrplt vlcdmdtdgg gwtvfqrryd gsvdfyrdwa tykqgfgsrl gefwlgndni181 haltaqgtse lrvdlvdfed nyqfakyrsf kvadeaekyn lvlgafvegs agdsltfhnn241 qsfstkdqdn dlntgncavm fqgawwyknc hvsnlngryl rgthgsfang inwksgkgyn301 ysykvsemkv rpaO70497.Ficolin 2 precursor(Collagen/fibrinogen domain-containing protein 2)(Ficolin-B)(Ficolin B)(Serum lectin P35)(EBP-37)(Hucolin)[gi:13124181]＜1..15/gene＝″FCN2″/region_name＝″Signal″/note＝″POTENTIAL″16..＞306/gene＝″FCN2″/region_name＝″Mature chain″/note＝″FICOLIN 2.″41..79/gene＝″FCN2″/region_name＝″Domain″/note＝″COLLAGEN-LIKE.″130..276/gene＝″FCN2″/region_name＝″Domain″/note＝″FIBRINOGEN C-TERMINAL.″299/gene＝″FCN2″/site_type＝″glycosylation″/note＝″N-LINKED(GLCNAC...)(POTENTIAL).″1 lgsaalfvlt ltvhaagtcp elkvldlegy kqltilqgcp glpgaagpkg eagakgdrge61 sglpgipgke gptgpkgnqg ekgirgekgd sgpsqscatg prtckelltq ghfltgwyti121 ylpdcrpmtv lcdmdtdggg wtvfqrrldg svdffrdwts ykrgfgsqlg efwlgndnih181 alttqgtsel rvdlsdfegk hdfakyssfq iqgeaekykl ilgnflggga gdsltphnnr241 lfstkdqdnd gstsscamgy hgawwysqch tsnlnglylr gphksyangv nwkswrgyny301 sckvseO70165.Ficolin 1 precursor(Collagen/fibrinogen domain-containing protein 1)(Ficolin-A)(Ficolin A)(M-Ficoli)[gi:3124179]1..22/gene＝″FCN1″/region_name＝″Signal″/note＝″POTENTIAL.″23..334/gene＝″FCN1″/region_name＝″Mature chain″/note＝″FICOLIN 1.″50..88/gene＝″FCN1″/region_name＝″Domain″/note＝″COLLAGEN-LIKE.″152..298/gene＝″FCN1″/region_name＝″Domain″/note＝″FIBRINOGEN C-TERMINAL.″261/gene＝″FCN1″/site_type＝″glycosylation″/note＝″N-LINKED(GLCNAC...)(POTENTIAL).″1 mqwptlwafs gllclcpsqa lgqergacpd vkvvglgaqd kvvviqscpg fpgppgpkge61 pgspagrger gfqgspgkmg pagskgepgt mgppgvkgek gdtgaapslg ekelgdtlcq121 rgprsckdll trgifltgwy tihlpdcrpl tvlcdmdvdg ggwtvfqrrv dgsidffrdw181 dsykrgfgnl gtefwlgndy lhlltangnq elrvdlqdfq gkgsyakyss fqvseeqeky241 kitlgqfleg tagdsltkhn nmsftthdqd ndansmncaa lfhgawwyhn chqsnlngry301 lsgshesyad ginwgtgqgh hysykvaemk irasP57756.Ficolin 2 precursor(Collagen/fibrinogen domain-containing protein 2)(Ficolin-B)(Ficolin B)(Serum lectin P35)(EBP-37)(Hucolin)[gi:13124114]1..22/gene＝″FCN2″/region_name＝″Signal″/note＝″POTENTIAL.″23..319/gene＝″FCN2″/region_name＝″Mature chain″/note＝″FICOLIN 2.″48..86/gene＝″FCN2″/region_name＝″Domain″/note＝″COLLAGEN-LIKE.″137..283/gene＝″FCN2″/region_name＝″Domain″/note＝″FIBRINOGEN C-TERMINAL.″306/gene＝″FCN2″/site_type＝″glycosylation″/note＝″N-LINKED(GLCNAC...)(POTENTIAL).″1 mvlgsaalfv lslcvteltl haadtcpevk vldlegsnkl tilqgcpglp galgpkgeag61 akgdrgesgl pghpgkagpt gpkgdrgekg vrgekgdtgp sqscatgprt ckelltrgyf121 ltgwytiylp dcrpltvlcd mdtdgggwtv fqrridgtvd ffrdwtsykq gfgsqlgefw181 lgndnihalt tqgtnelrvd ladfdgnhdf akyssfqiqg eaekyklilg nflgggagds241 ltsqnnmlfs tkdqdndqgs sncavryhga wwysdchtsn lnglylrglh ksyangvnwk301 swkgynysyk vsemkvrliJC5980.ficolin-A precurs-mouse[gi:7513652]1..21/region_name＝″domain″/note＝″signal sequence″50..64/region_name＝″domain″/note＝″collagen-like″68..106/region_name＝″domain″/note＝″collagen-like″123..334/region_name＝″domain″/note＝″fibrinogen beta/gamma homology#label FBG″1 mqwptlwafs gllclcpsqa lgqergacpd vkvvglgaqd kvvviqscpg fpgppgpkge61 pgspagrger gfqgspgkmg pagskgepgt mgppgvkgek gdtgaapslg ekelgdtlcq121 rgprsckdll trgifltgwy tihlpdcrpl tvlcdmdvdg ggwtvfqrrv dgsidffrdw181 dsykrgfgnl gtefwlgndy lhlltangnq elrvdlqdf qgkgsyakyss fqvseeqeky241 kitlgqfleg tagdsltkhn nmsftthdqd ndansmncaa lfhgawwyhn chqsnlngry301 lsgshesyad ginwgtgqgh hysykvaemk irasS61517.ficolin-1 precurs-human[gi:2135116]1..326/note＝″36K HLA-cross-reactive plasma protein；hucolin，35K″1..22/region_name＝″domain″/note＝″signal sequence″52..108/region_name＝″region″/note＝″collagen-like″115..326/region_name＝″domain″/note＝″fibrinogen beta/gamma homology#label FBG″305/site_type＝″binding″/note＝″carbohydrate(Asn)(covalent)″1 melsgatmar glavllvlfl hiknlpaqaa dtcpevkvvg legsdkltil rgcpglpgap61 gpkgeagvig ergerglpga pgkagpvgpk gdrgekgmrg ekgdagqsqs catgprnckd121 lldrgyflsg whniylpdcr pltvlcdmdt dgggwtvfqr rmdgsvdfyr dwaaykqgfg181 sqlgefwlgn dnihaltaqg sselrvdlvd fegnhqfaky ksfkvadeae kyklvlgafv241 ggsagnsltg hnnnffstkd qdndvsssnc aekfqgawwy adchasslng lylmgphesy301 anginwsaak gykysykvse mkvrpaA47172.transforming growth factor-beta 1-binding protein homolog ficolin-alpha-pig[gi:423206]112..323/region_name＝″domain″/note＝″fibrinogen beta/gamma homology#label FBG″1 mdtrgvaaam rplvllvafl ctaapaldtc pevkvvgleg sdklsilrgc pglpgaagpk61 geagasgpkg gqgppgapge pgppgpkgdr gekgepgpkg esweteqclt gprtckellt121 rghilsgwht iylpdcqplt vlcdmdtdgg gwtvfqrrsd gsvdfyrdwa aykrgfgsql181 gefwlgndhi haltaqgtne lrvdlvdfeg nhqfakyrsf qvadeaekym lvlgafvegn241 agdsltshnn slfttkdqdn dqyasncavl yqgawwynsc hvsnlngryl ggshgsfang301 vnwssgkgyn ysykvsemkf ratJC4942.ficolin-1 precursor-human[gi:2135117]1..22/region_name＝″domain″/note＝″signal sequence″45..101/region_name＝″region″/note＝″collagen-like″108..319/region_name＝″domain″/note＝″fibrinogen beta/gamma homology#label FBG″111..315/region_name＝″region″/note＝″fibrinogen-like″298/site_type＝″binding″/note＝″carbohydrate(Asn)(covalent)″1 marglavllv lflhiknlpa qaadtcpevk vvglegsdkl tilrgcpglp gapgpkgeag61 vigergergl pgapgkagpv gpkgdrgekg mrgekgdagq sqscatgprn ckdlldrgyf121 lsgwhtiylp dcrpltvlcd mdtdgggwtv fqrrmdgsvd fyrdwaaykq gfgsqlgefw181 lgndnihalt aqgsselrvd lvdfegnhqf akyksfkvad eaekyklvlg afvggsagns241 ltghnnnffs tkdqdndvss sncaekfqga wwyadchasn lnglylmgph esyanginws301 aakgykysyk vsemkvrpaAAF44911.symbol＝BG:DS00929...[gi:7287873]1 mkscffvlfl wtllfevgqs sphtcpsgsp ngihqlmlpe eepfqvtqck ttardwiviq61 rrldgsvnfn qswfsykdgf gdpngeffig lqklylmtre qphelfiqlk hgpgatvyah121 fddfqvdset elyklervgk ysgtagdslr yhinkrfstf drdndesskn caaehgggww181 fhsclsr所述第一多肽優(yōu)選包含所述補(bǔ)體激活蛋白或所述蛋白的變體或同系物的至少10個(gè)，如至少12個(gè)，例如至少15個(gè)，如至少20個(gè)，例如至少25個(gè)，如至少30個(gè)，例如至少35個(gè)，如至少40個(gè)，例如至少50個(gè)連續(xù)的氨基酸殘基。此類變體或同系物優(yōu)選與所述補(bǔ)體激活蛋白至少70％，如80％，例如90％，如95％相同。
所述融合蛋白的第一多肽序列在直接或間接與靶，如細(xì)菌或病毒結(jié)合時(shí)，優(yōu)選能夠活化凝集素補(bǔ)體途徑。優(yōu)選實(shí)施方案中所述第一多肽序列能夠連接至少一個(gè)MASP蛋白，如選自MASP-1，MASP-2和MASP-3的MASP蛋白或其功能同系物或變體。特別是當(dāng)所述第一多肽是融合蛋白的一部分時(shí)，它能夠連接所述至少一個(gè)MASP蛋白。因此，所述第一多肽序列能夠給所述融合蛋白提供激活補(bǔ)體系統(tǒng)的活性。
在特別優(yōu)選的實(shí)施方案中，所述第一多肽序列至少包含的氨基酸殘基，此氨基酸殘基對(duì)應(yīng)于圖1所示L-ficolin序列的1-54，如圖1的L-ficolin序列的1-55，如圖1的L-ficolin序列的1-69，如圖1的L-ficolin序列的1-77，如圖1的L-ficolin序列的1-90，如圖1的L-ficolin序列的1-93，如圖1的L-ficolin序列的1-131，如圖1的L-ficolin序列的1-207。特別是所述第一多肽序列包含選自如下的氨基酸殘基圖1的L-ficolin序列的1-55，圖1的L-ficolin序列的1-54，圖1的L-ficolin序列的1-50，或1-77。在更優(yōu)選的實(shí)施方案中，所述第一多肽序列具有選自如下的氨基酸殘基圖1的L-ficolin序列的1-55，圖1的L-ficolin序列的1-54，圖1的L-ficolin序列的1-50，或1-77。在另一實(shí)施方案中，所述第一多肽序列至少包含氨基酸殘基，所述氨基酸殘基對(duì)應(yīng)于圖1所示L-ficolin序列的60-90，如圖1的L-ficolin序列的55-90，如圖1的L-ficolin序列的54-92。
優(yōu)選選擇的所述第一多肽序列和所述第二多肽序列包括基序X-X-G-X-X-G至少5次，如至少7次，優(yōu)選在連續(xù)的序列中包括該基序。更優(yōu)選選擇所述第一多肽序列和所述第二多肽序列來(lái)使前述的基序被基序X-X-G-X-G取代一次。在所述基序中X表示任何不同于甘氨酸的氨基酸，而G表示甘氨酸。
第二多肽序列所述第二多肽序列優(yōu)選能夠連接一或多個(gè)糖。這可以通過(guò)至少引入目標(biāo)膠原凝集素的糖識(shí)別區(qū)來(lái)實(shí)現(xiàn)。因此，所述第二多肽序列優(yōu)選包含膠原凝集素或其同系物或變體的CRD區(qū)。
優(yōu)選所述膠原凝集素選自如下MBL(結(jié)合甘露糖的凝集素)，SP-A(肺表面活性蛋白A)，SP-D(肺表面活性蛋白D)，BK(或BC，牛共凝集素)和CL-43(膠原凝集素-43)。最優(yōu)選所述膠原凝集素是MBL。
在特別優(yōu)選的實(shí)施方案中所述膠原凝集素具有參照序列數(shù)據(jù)庫(kù)和登錄號(hào)如下所列的序列之一。
膠原凝集素SEQ ID NO42Q9NPY3 Complement component C1q receptor precursor(Complement component 1，qsubcomponent，receptor 1)(C1qRp)(C1qR(p))(C1q/MBL/SPA receptor)(CD93 antigen)(CDw93)gi|21759074|sp|Q9NPY3|CD93_HUMAN[21759074]FEATURES Location/Qualifiers source 1..652/organism＝″Homosapiens″/db_xref＝″taxon:9606″gene 1..652/gene＝″C1QR1″/note＝″CD93″Protein 1..652/gene＝″C1QR1″/product＝″Complement component C1q receptor precursor″Region 1..21/gene＝″C1QR1″/region_name＝″Signal″Region 22..652/gene＝″C1QR1″/region_name＝″Mature chain″/note＝″COMPLEMENTCOMPONENT C1Q RECEPTOR.″Region 22/gene＝″C1QR1″/region_name＝″Conflict″/note＝″T-＞V(IN AA SEQUENCE).″Region 24..580/gene＝″C1QR1″/region_name＝″Domain″/note＝″EXTRACELLULAR(POTENTIAL).″Region 32..174/gene＝″C1QR1″/region_name＝″Domain″/note＝″C-TYPE LECTIN.″Region 36/gene＝″C1QR1″/region_name＝″Conflict″/note＝″C-＞T(IN AA SEQUENCE).″Region 38..39/gene＝″C1QR1″/region_name＝″Conflict″/note＝″TA-＞RI(IN AASEQUENCE).″Region 155/gene＝″C1QR1″/region_name＝″Conflict″/note＝″S-＞N(IN REF.1).″Region 186/gene＝″C1QR1″/region_name＝″Conflict″/note＝″G-＞A(IN AA SEQUENCE).″Region 260..301/gene＝″C1QR1″/region_name＝″Domain″/note＝″EGF-LIKE 1″Bond bond(264，275)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY″Bond bond(271，285)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Bond bond(287，300)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY″Region 302..344/gene＝″C1QR1″/region_name＝″Domain″/note＝″EGF-LIKE 2.″Bond bond(306，317)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Bond bond(311，328)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Region 318/gene＝″C1QR1″/region_name＝″Variant″/note＝″V-＞A./FTld＝VAR_013573.″Site 325/gene＝″C1QR1″/site_type＝″glycosylation″/note＝″N-LINKED(GLCNAC...)(POTENTIAL).″Bond bond(330，343)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Region 345..384/gene＝″C1QR1″/region_name＝″Domain″/note＝″EGF-LIKE3，CALCIUM-BINDING(POTENTIAL).″Bond bond(349，358)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Bond bond(354，367)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Bond bond(369，383)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Region 385..426/gene＝″C1QR1″/region_name＝″Domain″/note＝″EGF-LIKE 4，CALCIUM-BINDING(POTENTIAL).″Bond bond(389，400)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Bond bond(396，409)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Bond bond(411，425)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Region 427..468/gene＝″C1QR1″/region_name＝″Domain″/note＝″EGF-LIKE 5，CALCIUM-BINDING(POTENTIAL).″Bond bond(431，443)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Bond bond(439，452)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY″Bond bond(454，467)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Region 492/gene＝″C1QR1″/region_name＝″Conflict″/note＝″S-＞A(IN AA SEQUENCE).″Region 496/gene＝″C1QR1″/region_name＝″Conflict″/note＝″R-＞Q(IN AA SEQUENCE).″Region 504/gene＝″C1QR1″/region_name＝″Conflict″/note＝″R-＞G(IN AA SEQUENCE).″Region 541/gene＝″C1QR1″/region_name＝″Conflict″/note＝″P-＞S(IN REF.1).″Region 581..601/gene＝″C1QR1″/region_name＝″Transmembraneregion″/note＝″POTENTIAL″Region 594..601/gene＝″C1QR1″/region_name＝″Domain″/note＝″POLY-LEU.″Region 602..652/gene＝″C1QR1″/region_name＝″Domain″/note＝″CYTOPLASMIC(POTENTIAL).″ORIGIN 1 matsmgllll llllltqpga gtgadteavv cvgtacytah sgklsaaeaq nhcnqnggnl61 atvkskeeaq hvqrvlaqll rreaaltarm skfwiglqre kgkcldpslp lkgfswvggg121 edtpysnwhk elrnsciskr cvsllldlsq pllpsrlpkw segpcgspgs pgsniegfvc181 kfsfkgmcrp lalggpgqvt yttpfqttss sleavpfasa anvacgegdk detqshyflc241 kekapdvfdw gssgplcvsp kygcnfnngg chqdcfeggd gsflcgcrpg frllddlvtc301 asrnpcsssp crggatcvlg phgknytcrc pqgyqldssq ldcvdvdecq dspcaqecvn361 tpggfrcecw vgyepggpge gacqdvdeca lgrspcaqgc tntdgsfhcs ceegyvlage421 dgtqcqdvde cvgpggplcd slcfntqgsf hcgclpgwvl apngvsctmg pvslgppsgp481 pdeedkgeke gstvpraata sptrgpegtp katpttsrps lssdapitsa plkmlapsgs541 pgvwrepsih hataasgpqe paggdssvat qnndgtdgqk lllfyilgtv vaillllala601 lgllvyrkrr akreekkekk pqnaadsysw vperaesram enqysptpgt dcSEQ ID NO43BAC05523 collectin placenta 1[Mus musculus]gi|21901969|dbj|BAC05523.1|[21901969]FEATURES Location/Qualifiers source 1..742/organism＝″Musmusculus″/db_xref＝″taxon:10090″/tissue_lib＝″Liver″Protein 1..742/product＝″collectin placenta 1″CDS1..742/gene＝″CL-P1″/coded_by＝″AB078434.1:92..2320″ORIGIN 1 mkddfaeeee vqsfgykrfg iqegtqctkc knnwalkfsi vllyilcall titvailgyk61 vvekmdnvtd gmetshqtyd nkltavesdl kklgdqagkk alstnselst frsdildlrq121 qlqeitekts knkdtleklq angdslvdrq sqlketlqnn sflittvnkt lqayngyvtn181 lqqdtsvlqg nlqsqmysqs vvimnlnnln ltqvqqrnli snlqqsvddt slaiqriknd241 fqnlqqvflq akkdtdwlke kvqslqtlaa nnsalakann dtledmnsql ssftgqmdni301 ttisqaneqs lkdlqdlhkd tenrtavkfs qleerfqvfe tdivniisni sytahhlrtl361 tsnlndvrtt ctdtltrhtd dltslnntlv nirldsislr mqqdmmrskl dtevanlsvv421 meemklvdsk hgqliknfti lqgppgprgp kgdrgsqgpp gptgnkgqkg ekgepgppgp481 agergtigpv gppgergskg skgsqgpKgs rgspgkpgpq gpsgdpgppg ppgkdglpgp541 qgppgtqglq gtvgepgvpg prglpglpgv pgmpgpkgpp gppgpsgame plalqneptp601 asevngcpph wknftdkcyy fslekeifed aklfcedkss hlvfinsree qqwikkhtvg661 reshwigltd seqesewkwl dgspvdyknw kagqpdnwgs ghgpgedcag liyagqwndf721 qcdeinnfic ekereavpss ilSEQ ID NO45AAM34742 46-kDa collectin precursor[Bos taurus]gi|21105685|gb|AAM34742.1|AF509589_1[21105685]sig_peptide 1..20Region 67..245/region_name＝″collagen-like region″Region 245..371/region_name＝″carbohvdrate recognition domain″CDS 1.371/gene＝″CL-46″/coded_by＝″ioin(AF509589.1:1454..1652，AF509589.1:5950..6066，AF509589.1:6402..6509，AF509589.1:6823..6930，AF509589.1:7289..7405，AF509589.1:8021..8104，AF509589.1:10318..10700)″ORIGIN 1 mlllplsvll lltqpwrslg aemkiysqkt langctlvvc rppegglpgr dgqdgregpq61 gekgdpgspg pagragrpgp agpigpkgdn gsagepgpkg dtgppgppgm pgpagregps121 gkqgsmgppg tpgpkgdtgp kggmgapgmq gspgpaglkg ergapgelga pgsagvagpa181 gaigpqgpsg argppglkgd rgdpgergak gesgladvna lkqrvtileg qlqrlqnafs241 rykkavlfpd gqavgkkifk tagavksysd aqqlcreakg qlasprsaae neavaqlvra301 knndaflsmn distegkfty ptgeslvysn wasgepnnnn agqpencvqi yregkwndvp361 csepllvice fSEQ ID NO47XP_139613 similar to collectin sub-family member 10；collectin liver 1；collectin 34[Musmusculus]gi|20903807|reg|XP_139613.1|[20903807]FEATURES Location/Qualifiers source 1..420/organism＝″Musmusculus″/strain＝″C57BL/6J″/db_xref＝″taxon:10090″/chromosome＝″15″Protein 1..420/product＝″similar to collectin sub-family member 10；collectin liver 1；collectin34″Region 152..269/region_name＝″C-type lectin(CTL)or carbohydrate-recognition domain(CRD)″/note＝″CLECT″/db_xref＝″CDD:smart00034″Region 165..269/region_name＝″Lectin C-typedomain″/note＝″lectin_c″/db_xref＝″CDD:pfam00059″Region 362..419/region_name＝″Ubiquitin-coniugating enzyme E2，catalytic domainhomologues″/note＝″UBCc″/db_xref＝″CDD:smart00212″Region 363..419/region_name＝″Ubiquitin-coniugatingenzyme″/note＝″UQ_con″/db_xref＝″CDD:pfam00179″CDS1..420/gene＝″LOC239447″/coded_by＝″XM_139613.1:1..1263″/db_xref＝″lnterimID:239447″ORIGIN 1 mngfrvllrs nlsmllllal lhfqslgldv dsrsaaevca thtispgpkg ddgergdtge61 egkdgkvgrq gpkgvkgelg dmgaqgnigk sgpigkkgdk gekgllgipg ekgkagticd121 cgryrkvvgq ldisvarlkt smkfiknvia gireteekfy yivqeeknyr eslthcrirg181 gmlampkdev vntliadyva ksgffrvfig vndleregqy vftdntplqn ysnwkeeeps241 dpsghedcve mlssgrwndt echltmyfvs slqedliedc lreqgllvqv tpanqellfg301 idtflgpmsc vyqrtgtkqk lysqcrlwdg lakkqtneta niatfckgae pnrgsrpcgq361 kqemmtlmms gnkgittfpe sdnlfkwvgt mlgaagtide dlkyklslns pvvtliihpqSEQ ID NO48XP_123211 simiar to collectin sub-family member 12[Mus musculus]gi|20876566|ref|XP_123211.1|[20876566]FEATURES Location/Qualifiers source 1..742/organism＝″Musmusculus″/strain＝″C57BL/6J″/db_xref＝″taxon:10090″/chromosome＝″18″Protein 1..742/product＝″similar to collectin sub-famliy member 12″Region 79..320/region_name＝″V-type ATPase 116kDa subunitfamily″/note＝″V_ATPase_sub_a″/db_xref＝″CDD:pfam01496″Region 92..337/region_name＝″Intermediate filamentprotein″/note＝″filament″/db_xref＝″CDD:pfam00038″Region 607..731/region_name＝″C-typelectin(CTL)or carbohydrate-recognition domain(CRD)″/note＝″CLECT″/db_xref＝″CDD:smart00034″Region 624..732/region name＝″Lectin C-typedomain″/note＝″lectin_c″/db_xref＝″CDD:pfam00059″CDS1..742/gene＝″LOC225157″/coded_by＝″XM_123211.1:77..2305″/db_xref＝″InterimID:225157″ORIGIN 1 mkddfaeeee vqsfgykrfg iqegtqctkc knnwalkfsi vllyilcall titvailgyk61 vvekmdnvtd gmetshqtyd nkltavesdl kklgdqagkk alstnselst frsdildlrq121 qlqeitekts knkdtleklq angdslvdrq sqlketlqnn sflittvnkt lqayngyvtn181 lqqdtsvlqg nlqsqmysqs vvimnlnnln ltqvqqrnli snlqqsvddt slaiqriknd241 fqnlqqvflq akkdtdwlke kvqslqtlaa nnsalakann dtledmnsql ssftgqmdni301 ttisqaneqs lkdlqdlhkd tenrtaykfs qleerfqvfe tdivniisni sytahhlrtl361 tsnlndvrtt ctdtltrhtd dltslnntlv nirldsislr mqqdmmrskl dtevenlsvv421 meemklvdsk hgqliknfti lqgppgprgp kgdrgsqgpp gptgnkgqkg ekgepgppgp481 agergtigpv gppgergskg skgsqgpkgs rgspgkpgpq gpsgdpgppg ppgkdglpgp541 qgppgfqglq gtvgepgvpg prglpglpgv pgmpgpkgpp gppgpsgame plalqneptp601 asevngcpph wknftdkcyy fslekeifed aklfcedkss hlvfinsree qqwikkhtvg661 reshwigltd seqesewkwl dgspvdyknw kagqpdnwgs ghgpgedcag liyagqwndf721 qcdeinnfic ekereavpss ilSEQ ID NO49NP_571645 mannose binding-like lectin[Danio rerio]gi|18858997|ref|NP_571645.1|[18858997]sig_peptide 1..23mat_peptide 24..251/product＝″mannose binding-like lectin″Region 24..36/region_name＝″N-terminal segment″Region 33..70/region_name＝″Collagen triple helix repeat(20copies)″/note＝″Collagen″/db_xref＝″CDD:pfam01391″Region 33..70/region_name＝″Collagen triple helix repeat(20copies)″/note＝″Collagen″/db_xref＝″CDD:pfam01391″Region 37..101/region_name＝″collagen-like structure″Region 37..70/region_name＝″Collagen triple helix xrepeat(20copies)″/note＝″Collagen″/db_xref＝″CDD:pfam01391″Region 71..74/region_name＝″break in collagen structure″Region 102..132/region_name＝″neck region″Region 133..251/region_name＝″carbohydrate recognition domain″/note＝″CRD″Region 134..247/region_name＝″C-type lectin(CTL)or carbohydrate-recognition domain(CRD)″/note＝″CLECT″/db_xref＝″CDD:smart00034″Region 146..247/region_name＝″Lectin C-typedomain″/note＝″lectin_c″/db_xref＝″CDD:pfam00059″CDS 1..251/gene＝″mbl″/coded_by＝″NM_131570.1:68..823″/note＝″collectin with structuralhomology to mannose-binding lectin but with a predicted carbohydrate specificity forgalactose；mannose binding-like lectin″/db_xref＝″LocusID:58091″ORIGIN 1 mallklflga lllllqlvql magaadpqsl ncpayagvpg tpghnglpgr dgrvgrdgan61 gpkgekgepg vnvqgppgka gppgpagakg ergpsglpgq dcmsdslkse lqklsdkial121 iekvvnfktf kkvgqkyyvt ddveetfdkg mqycssngga lvlprtleen allkvfvssa
181 fkrlfiritd rekegefvdt drkkltftnw gpnqpdnykg aqdcgaiads glwddvscds241 lypiceieikSEQ ID NO50NP_569057 collectin sub-family member 12，isoform l；scavenger receptor with C-type lectin；collectin placenta 1[Homo sapiens]gi|18641 360|ref|NP_569057.1|[18641360]FEATURES Location/Qualifiers source 1..742/organism＝″Homosapiens″/db_xref＝″taxon:9606″/chromosome＝″18″/map＝″18pter-p11.3″Protein 1..742/product＝″collectin sub-family member 12，isoform l″/note＝″isoform l isencoded by transcript variant l；scavenger receptor with C-type lectin；collectin placenta 1″Region 79..328/region_name＝″V-type ATPase 116kDa subunitfamily″/note＝″V_ATPase_sub_a″/db_xref＝″CDD:pfam01496″Region443..589/region_name＝″collagen-like domain″Region 607..731/region_name＝″C-type lectin(CTL)or carbohydrate-recognition domain(CRD)″/note＝″CLECT″/db_xref＝″CDD:smart00034″Region 624..732/region_name＝″Lectin C-typedomain″/note＝″lectin_c″/db_xref＝″CDD:pfam00059″Region668..719/region_name＝″Beta-lactamase″/note＝″beta-lactamase″/db_xref＝″CDD:pfam00144″CDS1..742/gene＝″COLEC12″/coded_by＝″NM_130386.1:172..2400″/db_xref＝″LocusID:81035″ORIGIN 1 mkddfaeeee vqsfgykrfg iqegtqctkc knnwaIkfsi illyiIcaIl titvailgyk61 vvekmdnvtg gmetsrqtyd dkltavesdl kklgdqtgkk aistnselst frsdildlrq121 qlreitekts knkdtleklq asgdalvdrq sqlketlenn sflittvnkt lqayngyvtn181 lqqdtsvlqg nlqnqmyshn vvimnlnnln ltqvqqrnli tnlqrsvddt sqaiq riknd241 fqnlqqvflq akkdtdwlke kvqslqtlaa nnsalakann dtledmnsql nsftgqmeni301 ttisqaneqn lkdlqdlhkd aenrtaikfn qleerfqlfetdivniisni sytahhlrtl361 tsnlneyrtt ctdtltkhtd dltslnntla nirldsvslr mqqdlmrsrl dtevanlsvi421 meemklvdsk hgqliknfti lqgppgprgp rgdrgsqgpp gptgnkgqkg ekgepgppgp481 agergpigpa gppgerggkg skgsqgpkgs rgspgkpgpq gpsgdpgppg ppgkeglpgp541 qgppgfqglq gtvgepgvpg prglpglpgv pgmpgpkgpp gppgpsgavv plalqneptp601 apedngcpph wknftdkcyy fsvekeifed aklfcedkss hlvfintree qqwikkqmvg661 reshwigltd serenewkwl dgtspdyknw kagqpdnwgh ghgpgedcag liyagqwndf721 qcedvnnfic ekdretvlss alSEQ ID NO51NP_110408 collectin sub-family member 12，isoform ll；scavenger receptor with C-type lectin；collectin placenta 1[Homo sapiens]gi|18641358|ref|NP_110408.2|[18641358]FEATURES Location/Qualifiers source 1..622/organism＝″Homosepiens″/db_xref＝″taxon:9606″/chromosome＝″18″/map＝″18pter-p11.3″Protein 1..622/product＝″collectin sub-family member 12，isoform ll″/note＝″isoform ll isencoded by transcript variant ll；scavenger receptor with C-type lectin；collectin placenta 1″Region 79..328/region_name＝″V-type ATPase 116kDa subunitfamily″/note＝″V_ATPase_sub_a″/db_xref＝″CDD:pfam01496″Region 443..589/region_name＝″collagen-like domain″CDS1..622/gene＝″COLEC12″/coded_by＝″NM_030781.2:172..2040″/db_xref＝″LocusID:81035″ORIGIN 1 mkddfaeeee vqsfgykrfg iqegtqctkc knnwalkfsi illyilcall titvailgyk61 vvekmdnvtg gmetsrqtyd dkltayesdl kklgdqtgkk aistnselst frsdildlrq121 qlreitekts knkdtleklq asgdalvdrq sqlketlenn sflittvnkt lqayngyvtn181 lqqdtsvlqg nlqnqmyshn vvimnlnnln ltqvqqrnli tnlqrsvddt sqaiqriknd241 fqnlqqvflq akkdtdwlke kvqslqtlaa nnsalakann dtledmnsql nsftgqmeni301 ttisqaneqn lkdlqdlhkd aenrtaikfn qleerfqlfe tdivniisni sytahhlrtl361 tsnlnevrtt ctdtltkhtd dltslnntla nirldsvslr mqqdlmrsrl dtevanlsvi421 meemklvdsk hgqliknfti lqgppgprgp rgdrgsqgpp gptgnkgqkg ekgepgppgp
481 agergpigpa gppgerggkg skgsqgpkgs rgspgkpgpq gpsgdpgppg pp9keglpgp541 qgppgfqglq gtvgepgvpg prglpglpgv pgmpgpkgpp gppgpsgavv plalqneptp601 apednskskp slqpggqgsa caSEQ ID NO52NP_569716 collectin sub-family member 12[Mus musculus]gi|18485494|ref|NP_569716.1|[18485494]FEATURES Location/Qualifiers source 1..742/organism＝″Musmusculus″/db_xref＝″taxon:10090″Protein 1..742/product＝″collectin sub-family member 12″Region 79..320/region_name＝″V-type ATPase 116kDa subunitfamily″/note＝″V_ATPase_sub_a″/db_xref＝″CDD:pfam01496″Region 607..731/region_name＝″C-type lectin(CTL)or carbohydrate-recognition domain(CRD)″/note＝″CLECT″/db_xref＝″CDD:smart00034″Region 629..732/region_name＝″Lectin C-typedomain″/note＝″lectin_c″/db_xref＝″CDD:pfam00059″CDS1..742/gene＝″Colec12″/coded_by＝″NM_130449.1:77..2305″/db_xref＝″LocusID:140792″/dbxref＝″MGD:2152907”O(jiān)RIGIN 1 mkddfaeeee vqsfgykrfg ihegtqctkc innwalkfsi vllyilcall titvailgyk61 vvekmdnvsd gmetshqtyd nkltavesdl kklgdqagkk alstnselst frsdildlrq121 qlqeitekts knkdtleklq angdslvdrq sqlketlqnn sflittvnkt lqayngyvtn181 lqqdtnvlqg nlqsqmysqs vvimnlnnln ltqvqqrnli snlqqsvddt slaiqriknd241 fqnlqqvflq akkdtdwlke kvqslqtlaa nnsalakann dtledmnsql ssftgqmdni301 ttisqaneqs lkdlqdlhkd tanrtavkfs qleerfqvfe tdivniisni sytahhlrtl361 tsnlndvwtt ctdtltrhtd dltslnntlv nirldsislr mqqdmmrskl dtevanlsvv421 meemklvdsk hgqliknfti lqgppgprgp kgdrgsqgpp gptgnkgqkg ekgepgppgp481 agergtigpv gppgergskg skgsqgpkgs rgspgkpgpq gpsgdpgppg ppgkdglpgp541 qgppgfqglq gtvgepgvpg prglpglpgv pgmpgpkgpp gppgpsgame plalqneptp601 asevngcpph wknftdkcyy fslekeiled aklfcedkss hlvfinsree qqwikkhtvg661 reshwigltd seqesewkwl dgspvdyknw kagqpdnwgs ghgpgedcag liyagqwndf721 qcdeinnfic ekereavpss ilSEQ ID NO53AAL61856 43kDa collectin precursor[Bos taurus]gi|18252111|gb|AAL61856.1|[18252111]FEATURES Location/Qualifiers source 1..321/organism＝″Bos taurus″/db_xref＝″taxon:9913″Protein 1..321/product＝″43kDa collectin precursor″/name＝″CL-43；conglutinin；SP-D″Region 1..166/region_name＝″collagen-like″Region 167..193/region_name＝″alpha-helical neck″Region 195..321/region_name＝″carbohydrate-recognition domain″CDS 1..321/gene＝″CL43″/coded_by＝″join(AY071822.1:2945..3143，AY071822.1:5843..5950，AY071822.1:6273..6344，AY071822.1:6734..6850，AY071822.1:7039..7122，AY071822.1:9525..9910)″ORIGIN 1 mlplplsill lltqsqsflg eemdvysekt ltdpctlvvc appadslrgh dgrdgkegpq61 gekgdpgppg mpgpagregp sgrqgsmgpp gtpgpkgepg peggvgapgmpgspgpaglk121 gergtpgpgg aigpqgpsga mgppglkgdr gdpgekgarg etsvlevdtl rqrmrnlege181 vqrlqnivtq yrkavlfpdg qavgekifkt agavksysda eqlcreakgq lasprssaen241 eavtqlvrak nkhaylsmnd iskegkftyp tggsldysnw apgepnnrak degpenclei301 ysdgnwndie creerlvice fSEQ ID NO44AAL61855 43kDa collectin precursor[Bos taurus]gi|18252109|gb|AAL61855.1|[18252109]FEATURES Location/Qualifiers source 1..321/organism＝″Bostaurus″/db_xref＝″taxon:9913″/tissue_type＝″liver″Protein 1..321/product＝″43kDa collectinprecursor″/name＝″CL-43；conglutinin；SP-D″CDS1..321/gene＝″CL43″/coded_by＝″AY071821.1:172..1137″ORIGIN 1 mlplplsil lltqsqsflg eemdvysekt ltdpctlvvc appadslrgh dgrdgkegpq61 gekgdpgppg mpgpagregp sgrqgsmgpp gtpgpkgepg peggvgapgmpgspgpaglk121 gergtpgpgg aigpqgpsga mgppglkgdr gdpgekgarg etsvlevdtl rqrmrnlege181 vqrlqnivtq yrkavlfpdg qavgekifkt agavksysda eqlcreakgq lasprssaen241 eavtqlvrak nkhaylsmnd iskegkftyp tggsldysnw apgepnnrak degpenclei30 ysdgnwndie creerlvice fSEQ ID NO46BAB22581 data source:SPTR，source key:Q9Y6Z7，evidence:ISS～homolog to COLLECTIN34～putative[Mus musculus]gi|12833584|dbj|BAB22581.1|[12833584]FEATURES Location/Qualifiers source 1..272/organism＝ ″Musmusculus″/strain＝″C57BL/6J″/db_xref＝″FANTOM_DB:101O001H16″/db_xref＝″MGD:1904296″/db_xref＝″taxon:10090″/clone＝″1010001H16″/sex＝″male″/tissue_type＝″heart″/clone_lib＝″RIKEN full-length enriched mouse cDNA library″/dev_stage＝″adult″Protein 1..272/name＝″data source:SPTR，source key:Q9Y6Z7，evidence:ISS homolog toCOLLECTIN 34 putatiye″CDS1..272/coded_by＝″AK003121.1:81..899″/db_xref＝″MGD:1918943″ORIGIN 1 mmmrdlalag mlislaflsl lpsgcpqqtt edacsvqilv pglkgdagek gdkgapgrpg61 rvgptgekgd mgdkgqkgtv grhgkigpig akgekgdsgd igppgpsgep gipcecsqlr121 kaigemdnqv tqlttelkfi knavagvret eskiyllvke ekryadaqls cqarggtlsm181 pkdeaanglm asylaqagla rvfigindle kegafvysdr spmqtfnkwr sgepnnayde241 edcvemvasg gwndvachit myfmcefdke nlSEQ ID NO54NP_034905 mannose binding lectin，liver(A)[Mus musculus]gi|6754654|ref|NP_034905.1|[6754654]FEATURES Location/Qualifiers source 1..239/organism＝″Musmusculus″/db_xref＝″taxon:10090″/chromosome＝″14″/map＝″14 15.0 cM″Protein 1..239/product＝″mannose binding lectin，liver(A)″misc_feature 19..239/partial/note＝″mature protein based on homology to rat MPB-A″Region 126..236/region_name＝″C-type lectin(CTL)or carbohvdrate-recognition domain(CRD)″/note＝″CLECT″/db_xref＝″CDD:smart00034″Region 135..237/region_name＝″Lectin C-typedomain″/note＝″lectin_c″/db_xref＝″CDD:pfam00059″CDS1..239/gene＝″Mbl1″/coded_by＝″NM_010775.1:121..840″/db_xref＝″LocusID:17194″/db_xref＝″MGD:96923”O(jiān)RIGIN 1 mlllpllpvl lcvvsvsssg sqtcedtlkt csviacgrdg rdgpkgekge pgqglrglqg61 ppgklgppgs vgspgspgpk gqkgdhgdnr aieeklanme aeirilkskl qltnklhafs121 mgkksgkklf vtnhekmpfs kvkslctelq gtvaiprnae enkaiqevat giaflgitde181 ategqfmyvt ggrltysnwk kdepnnhgsg edcviildng lwndiscqas fkavcefpaSEQ ID NO55NP_034906 mannose binding lectin，serum(C)[Mus musculus]gi|6754656|ref|NP_034906.1|[6754656]sig_peptide 1..18Region 120..241/region_name＝″C-type lectin(CTL)or carbohydrate-recognition domain(CRD)″/note＝″CLECT″/db_xre＝″CDD:smart00034″Region 140..242/region_name＝″Lectin C-tvpedomain″/note＝″lectin_c″/db_xref＝″CDD:pfam00059″CDS 1..244/gene＝″Mbl2″/coded_by＝″NM_010776.1:177..911″/note＝″polysaccharide-bindingcomponent of RaRF；sequence similarity to mannose-bindingproteins″/db_xref＝″LocusID:17195″/db_xref＝″MGD:96924″ORIGIN 1 msiftsflll cvvtvvyaetltegvqnscp vvtcsspgln gfpgkdgrdg akgekgepgq61 glrglqgppg kvgptgppgn pglkgavgpk gdrgdraefd tseidseiaa lrselralrn121 wvlfslsekv gkkyfvssvk kmsldrvkal csefqgsvat prnaeensai qkvakdiayl181 gitdvrvegs fedltgnrvr ytnwndgepn ntgdgedcvv ilgngkwndv pcsdsflaic241 efsdSEQ ID NO56NP_006429 collectin sub-family member 10；collectin liver 1；collectin 34[Homo sapiens]gi|5453619|ref|NP_006429.1|[5453619]FEATURES Location/Qualifiers source 1..277/organism＝″Homosapiens″/db_xref＝″taxon:9606″/chromosome＝″8″/map＝″8q23-q24.1″Protein 1..277/product＝″collectin sub-family member 10″/note＝″collectin liver 1；collectin 34″Region 152..271/region_name＝″C-type lectin(CTL)or carbohydrate-recognition domain(CRD)″/note＝″CLECT″/db_xref＝″CDD:smart00034″Region 165..272/region_name＝″Lectin C-typedomain″/note＝″lectin_c″/db_xref＝″CDD:pfam00059″CDS1..277/gene＝″COLEC10″/coded_by＝″NM_006438.2:76..909″/db_xref＝″LocusID:10584″ORIGIN 1 mngfasllrr nqfillvlfl lqiqslgldi dsrptaevca thtispgpkg ddgekgdpge61 egkhgkvgrm gpkgikgelg dmgdrgnigk tgpigkkgdk gekgllgipg ekgkagtvcd121 cgryrkfvgq ldisiarlkt smkfvknvia gireteekfy yivqeeknyr eslthcrirg181 gmlampkdea antliadyva ksgffrvfig vndleregqy mftdntplqn ysnwnegeps241 dpyghedcve mlssgrwndt echltmyfvc efikkkkSEQ ID NO57BAB72147 collectin placenta 1[Homo sapiens]gi|17026101|dbj|BAB72147.1|[17026101]FEATURES Location/Qualifiers source 1..742/organism＝″Homosapiens″/db_xref＝″taxon:9606″/sex＝″female″/tissue_lib＝″placenta″Protein 1..742/product＝″collectin placenta 1″CDS 1..742/gene＝″CL-P1″/coded_by＝″AB005145.1:71..2299″ORIGIN 1 mkddfaeeee vqsfgykrfg iqegtqtkc knnwalkfsi illyilcall titvailgyk61 vvekmdnvtg gmetsrqtyd dkltavesdl kklgdqtgkk aistnselst frsdildlrq121 qlreitekts knkdtleklq asgdalvdrq sqlketlenn sflittvnkt lqayngyvtn181 lqqdtsvlqg nlqnqmyshn vvimnlnnln ltqvqqrnli tnlqrsvddt sqaiqriknd241 fqnlqqvflq akkdtdwlke kvqslqtlaa nnsalakann dtledmnsql nsftgqmeni301 ttisqaneqn lkdlqdlhkd aenrtaikfn qleerfqlfe tdivniisni sytahhlrtl361 tsnlnevrtt ctdtltkhtd dltslnntla nirldsvslr mqqdlmrsrl dtevanlsvi421 meemklvdsk hgqliknfti lqgppgprgp rgdrgsqgpp gptgnkgqkg ekgepgppgp481 agergpigpa gppgerggkg skgsqgpkgs rgspgkpgpq gpsgdpgppg ppgkeglpgp541 qgppgfqglq gtvgepgvpg prglpglpgv pgmpgpkgpp gppgpsgavv plalqneptp601 apedngcpph wknftdkcyy fsvekeifed aklfcedkss hlvfintree qqwikkqmvg661 reshwigltd serenewkwl dgtspdyknw kagqpdnwgh ghgpgedcag liyagqwndf721 qcedvnnfic ekdretvlss alSEQ ID NO58AAF63470 mannose binding-like lectin precursor[Carassius auratus]gi|7542474|gb|AAF63470.1|AF227739_1[7542474]sig_peptide＜1..13Region 14..25/region_name＝″N-terminal segment″Region 26..93/region_name＝″collagen-like structure″Region 60..63/region_name＝″break in collagen structure″Region 94..124/region_name＝″neck region″Region 125..246/region_name＝″carbohydraterecognition domain″/note＝″CRD″CDS 1..246/gene＝″MBL″/coded_by＝″AF227739.1:＜1..742″/note＝″collectin with structuralhomology to mannose-binding lectin but with a predicted carbohydrate specificity forgalactose″ORIGIN 1 llllqfalql ldgaepqnln cpayggvpgt pghnglpgrd grdgkdgaig pkgekgesgv61 svqgppgkag ppgtagekge rgpsgpqgsp gsesvleslk seiqqlkaki atfekvssvc121 hfrkvgqkyy itdgvvgnfd qglkscmefg gtmvsprtsa enqallklvv ssglgskkpy181 igvtdrkteg qfvdtegkql tftnwgpgqp ddykglqdcg viedtglwdd ggcgdirpim241 ceidikSEQ ID NO59AAF63469 mannose binding-like lectin precursor[Danio rerio]gi|7542472|gb|AAF63469.1|AF227738_1[7542472]sig_peptide 1..23mat_peptide 24..251/product＝″mannose binding-like lectin″Region 24..36/region_name＝″N-terminal segment″Region 37..101/region_name＝″colagen-like structure″Region 71..74/region_name＝″break in collagen structure″Region 102..132/region_name＝″neck region″Region 133..251/region_name＝″carbohydrate recognition domain″/note＝″CRD″CDS 1..251/gene＝″mbl″/coded_by＝″AF227738.1:68..823″/note＝″collectin with structuralhomology to mannose-binding lectin but with a predicted carbohydrate specificity forgalactose″ORIGIN 1 mallklflga llllqlvlql magaadpqsl ncpayagvpg tpghnglpgr dgrvgrdgan61 gpkgekgepg vnvqgppgka gppgpagakg ergpsglpgq dcmsdslkse lqklsdkial121 iekvvnfktf kkvgqkyyvt ddveetfdkg mqycssngga lvlprtleen allkvfvssa181 fkrlfiritd rekegefvdt drkkltftnw gpnqpdnykg aqdcgaiads glwddvscds241 lypiiceiei kSEQ ID NO60AAF63468 mannose binding-like lectin precursor[Cyprinus carpio]gi|7542470|gb|AAF63468.1|AF227737_1[7542470]sig_peptide 1..23mat_peptide 24..256/product＝″mannose binding-like lectin″Region 24..35/region_name＝″N-terminal segment″Region 36..103/region_name＝″collagen-like structure″Region 70..73/region_name＝″break in collagen structure″Region 104..134/region_name＝″neck region″Region 135..256/region name＝″carbohydrate recognition domain″/note＝″CRD″CDS 1..256/gene＝″MBL″/coded_by＝″AF227737.1:67..837″/note＝″collectin with structuralhomology to mannose-binding lectin but with a predicted carbohydrate specificity forgalactose″ORIGIN 1 malfklflgt llllqfalql ldgaepqnln cpayggvpgt pghnglpgrd grdgkdgaig61 pkgekgesgv svqgppgkag ppgpagekge rgptgsqgsp gsesvleslk seiqqlkaki121 atfekvasvg hfrqvgqkyy itdgvvgtfd qglkfckdfg gtmvfprtsa enqallklvv181 ssglsskkpy igvtdreteg rfvntegkql tftnwgpgqp ddykglqdcg viedsglwdd241 gscgdirpim ceidnkSEQ ID NO61AAK97540 surfactant protein A precursor[Gallus gallus]gi|15420996|gb|AAK97540.1|AF411083_1[15420996]sig_peptide 1..18Region 19..34/region_name＝″N-terminal segment″Region 35..43/region_name＝″putative collagen structure″Region 44..76/region_name＝″putative coil structure″Region 77..97/region_name＝″alpha-helical coil-coil structure；neck region″Region 98..222/region_name＝″carbohydrate recognition domain″Site 121..123/site_type＝″glycosylation″Site 181..183/site_type＝″glycosylation″/note＝″conserved″CDS 1..222/gere＝″SP-A″/coded_by＝″AF411083.1:61..729″ORIGIN 1 mlsysfcmia aavalltpch aqncagapel psipgvsgll glgalkryfg sllwpygeek61 lpecqwlqrq qdlstssdde lgnvllnlrq rilqlegvla ldgkitkvge kifasngkev121 nfssalesce etggtlatpm neeenkaimg ivkqynryay lgikesdtag qfkyvnnqpl181 nytswqqyep ngkgtekcve mytdgnwkdr kcnlyrltvc eySEQ ID NO62JN0450 conglutinin precursor-bovine gi|346501|pir||JN0450[346501]FEATURES Location/Qualifiers source 1..371/organism＝″Bos taurus″/db_xref＝″taxon:9913″Protein 1..371/product＝″conglutinin precursor″/note＝″C3b-binding protein″Region 1..20/region_name＝″domain″/note＝″signal sequence″Region 21..371/region_name＝″product″/note＝″conglutinin″Region 46..214/region_name＝″region″/note＝″collagen-like″Site 63/site_type＝″binding″/note＝″carbohydrate(Lys)(covalent)″Site 63/site_type＝″modified″/note＝″5-hydroxylysine(Lys)″Region 75..371/region_name＝″product″/note＝″conglutinin-N″Site 78/site_type＝″modified″/note＝″4-hydroxyproline(Pro)″Site 87/site_type＝″binding″/note＝″carbohydrate(Lys)(covalent)″Site 87/site_type＝″modified″/note＝″5-hydroxylysine(Lys)″Site 96/site_type＝″modified″/note＝″4-hydroxyproline(Pro)″Site 99/site_type＝″binding″/note＝″carbohydrate(Lys)(covalent)″Site 99/site_type＝″modified″/note＝″5-hydroxylysine(Lys)″Site 108/site_type＝″modified″/note＝″4-hydroxyproline(Pro)″Site 111/site_type＝″modified″/note＝″4-hydroxyproline(Pro)″Site 129/site_type＝″modified″/note＝″4-hydroxyproline(Pro)″Site 132/site_type＝″modified″/note＝″4-hydroxyproline(Pro)″Site 135/site_type＝″binding″/note＝″carbohydrate(Lys)(covalent)″Site 135/site_type＝″modified″/note＝″5-hydroxylysine(Lys)″Site 141/site_type＝″binding″/note＝″carbohydrate(Lys)(covalent)″Site 141/site_type＝″modified″/note＝″5-hydroxylysine(Lys)″Site 147/site_type＝″modified″/note＝″4-hydroxyproline (Pro)″Site 153/site_type＝″modified″/note＝″4-hydroxyproline(Pro)″Site 159/site_type＝″binding″/note＝″carbohydrate(Lys)(covalent)″Site 159/site_type＝″modified″/note＝″5-hydroxylysine(Lys)″Site 162/site_type＝″binding″/note＝″carbohydrate(Lys)(covalent)″Site 162/site_type＝″modified″/note＝″5-hydroxylysine(Lys)″Site 171/site_type＝″modified″/note＝″4-hydroxyproline(Pro)″Site 195/site_type＝″modified″/note＝″4-hydroxyproline(Pro)″Site 198/site_type＝″binding″/note＝″carbohydrate(Lys)(covalent)″Site 198/site_type＝″modified″/note＝″5-hydroxylysine(Lys)″Site 210/site_type＝″binding″/note＝″carbohydrate(Lys)(covalent)″Site 210/site_type＝″modified″/note＝″5-hydroxylysine(Lys)″Region 248..369/region_name＝″domain″/note＝″C-type lectin homology#label LCH”Site 337/site_type＝″binding″/note＝″carbohydrate(Asn)(covalent)″ORIGIN 1 mlllplsvll lltqpwrslg aemttfsqki lanactlvmc splesglpgh dgqdgrecph61 gekgdpgspg pagragrpgw vgpigpkgdn gfvgepgpkg dtgprgppgm pgpagregps121 gkqgsmgppg tpgpkgetgp kggvgapgiq gfpgpsglkg ekgapgetga pgragvtgps181 gaigpqgpsg argppglkgd rgdpgetgak gesglaevna lkqrvtildg hlrrfqnafs241 qykkavlfpd gqavgekifk tagavksysd aeqlcreakg qlasprssae neavtqmvra301 qeknaylsmn distegrfty ptgeilvysn wadgepnnsd egqpencvei fpdgkwndvp361 cskqllvice fSEQ ID NO63A57250 mannan-binding protein-chicken(fragment)gi|1362725|pir||A57250[1362725]FEATURES Location/Qualifiers source 1..30/organism＝″Gallus gallus″/db_xref＝″taxon:9031″Protem 1..30/product＝″mannan-binding protein″/note＝″collectin″Site 28/site_type＝″modified″/note＝″4-hydroxyproline(Pro)″ORIGIN 1 lltcdkpeek myscpiiqcs apavnglpggdSEQ ID NO64A53570 collectin-43-bovine gi|1083017|pir||A53570[1083017]FEATURES Location/Qualifiers source 1..301/organism＝″Bos taurus″/db_xref＝″taxon:9913″Protein 1..301/product＝″collectin-43″/note＝″lectin CL-43″Region 177..299/region_name＝″domain″/note＝″C-type lectin homology#label LCH″ORIGIN 1 eemdvysekt ltdpctlvvc appadslrgh dgrdgkegpq gekgdpgppg mpgpagregp61 sgrqgsmgpp gtpgpkgepg peggvgapgm pgspgpaglk gergapgpgg aigpqgpsga121 mgppglkgdr gdpgekgarg etsvlevdtl rqrmrnlege vqrlqnivtq yrkavlfpdg181 qavgekifkt agavksysda eqlcreakgq lasprssaen eavtqlvrak nkhaylsmnd241 iskegkftyp tggsldysnw apgepnnrak degpenclei ysdgnwndie creerlvice301 fSEQ ID NO65AAF28384 lung surfactant protein A[Sus scrofa]gi|6782434|gb|AAF28384.1|AF133668_1[6782434]FEATURES Location/Qualifiers source 1..116/organism＝″Sus scrofa″/db_xref＝″taxon:9823″Protein＜1..116/product＝″lung surfactant protein A″/function＝″involved in the innate immunesystem and lipid homeostasis within the lung″/name＝″collectin；SPA；SP-A″CDS 1..116/gene＝″SFTPA″/coded_by＝″AF133668.1:＜1..353″ORIGIN 1 avgekvfstn gqsvafdvir elcaraggri aaprspeene aiasivkkhn tyaylglveg61 ptagdffyld gtpvnytnwy pgeprgrgke kcvemytdgq wndrncqqyr laicefSEQ ID NO66AAF22145 lung surfactant protein D precursor；SPD；SP-D；CP4[Sus scrofa]gi|6760482|gb|AAF22145.2|AF132496_1[6760482]sig_peptide 1..20mat_peptide 21..378/product＝″lung surfactant protein D″CDS 1..378/gene＝″SFTPD″/coded_by＝″AF132496.2:44..1180″ORIGIN 1 mlllplsvli lltqpprslg aemktysqra vanacalvmc spmenglpgr dgrdgregpr61 gekgdpglpg avgragmpgl agpvgpkgdn gstgepgakg digpcgppgp pgipgpagke121 gpsgqqgnig ppgtpgpkge tgpkgevgal gmqgstgarg paglkgerga pgergapgsa181 gaagpagatg pqgpsgargp pglkgdrgpp gergakgesg lpgitalrgq vetlqgqvqr241 lqkafsqykk velfpngrgv gekifktggf ektfqdaqqv ctqaggqmas prseteneal301 sqlvtaqnka aflsmtdikt egnftyptge plvyanwapg epnnnggssg aencveifpn361 gkwndkacge lrlvicefSEQ ID NO67P41 317 MANNOSE-BINDING PROTEIN C PRECURSOR(MBP-C)(MANNAN-BINDINGPROTEIN)(RA-REACTIVE FACTOR P28A SUBUNIT)(RARF/P28A)gi|1346477|sp|P41317|MABC_MOUSE[1346477]FEATURES Location/Qualifiers source 1..244/organism＝″Musmusculus″/db_xref＝″taxon:10090″gene 1..244/gene＝″MBL2″Protein 1..244/gene＝″MBL2″/product＝″MANNOSE-BINDING PROTEIN C PRECURSOR″Region 1..18/gene＝″MBL2″/region_name＝″Signal″/note＝″BY SIMILARITY.″Region 3/gene＝″MBL2″/region_name＝″Conflict″/note＝″I-＞L(IN REF.1).″Region 15/gene＝″MBL2″/region_name＝″Conflict″/note＝″V-＞A(IN REF.1).″Region 19..244/gene＝″MBL2″/region_name＝″Mature chain″/note＝″MANNOSE-BINDINGPROTEIN C.″Bond bond(29)/gene＝″MBL2″/bond_type＝″disulfide″/note＝″INTERCHAIN(BYSIMILARITY).″Bond bond(34)/gene＝″MBL2″/bond_type＝″disulfide″/note＝″INTERCHAIN(BYSIMILARITY).″Region 38..96/gene＝″MBL2″/region_name＝″Domain″/note＝″COLLAGEN-LIKE(G-X-Y).″Site 43/gene＝″MBL2″/site_type＝″hydroxylation″/note＝″(POTENTIAL).″Site 58/gene＝″MBL2″/site_type＝″hydroxylation″/note＝″(POTENTIAL).″Site 69/gene＝″MBL2″/site_type＝″hydroxylation″/note＝″(POTENTIAL).″Site 78/gene＝″MBL2″/site_type＝″hydroxylation″/note＝″(POTENTIAL).″Site 81/gene＝″MBL2″/site_type＝″hydroxylation″/note＝″(POTENTIAL).″Region 149..242/gene＝″MBL2″/region_name＝″Domain″/note＝″C-TYPE LECTIN(SHORTFORM).″Bond bond(151，240)/gene＝″MBL2″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Bond bond(218，232)/gene＝″MBL2″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″ORIGIN 1 msiftsflll cvvtvvyaet ltegvqnscp vvtcsspgln gfpgkdgrdg akgekgepgq61 glrglqgppg kvgptgppgn pglkgavgpk gdrgdraefd tseidseiaa lrselralrn121 wvlfslsekv gkkyfvssvk kmsldrvkal csefqgsvat prnaeensai qkvakdiayl181 gitdvrvegs fedltgnrvr ytnwndgepn ntgdgedcvv ilgngkwndv pcsdsflaic241 efsdSEQ ID NO68P39039 MANNOSE-BINDING PROTEIN A PRECURSOR(MBP-A)(MANNAN-BINDINGPROTEIN)(RA-REACTIVE FACTOR POLYSACCHARIDE-BINDING COMPONENT P28BPOLYPEPTIDE)(RARF P28B)gi|729972|sp|P39039|MABA_MOUSE[729972]FEATURES Location/Qualifiers source 1..239/organism＝″Musmusculus″/db_xref＝″taxon:10090″gene 1..239/gene＝″MBL1″Protein 1..239/gene＝″MBL1″/product＝″MANNOSE-BINDING PROTEIN A PRECURSOR″Region 1..17/gene＝″MBL1″/region_name＝″Signal″/note＝″BY SIMILARITY.″Region 18..239/gene＝″MBL1″/region_name＝″Mature chain″/note＝″MANNOSE-BINDINGPROTEIN A.″Region 37..8g/gene＝″MBL1″/region_name＝″Domain″/note＝″COLLAGEN-LIKE(G-X-Y).″Region 144..239/gene＝″MBL1″/region_name＝″Domain″/note＝″C-TYPE LECTIN(SHORTFORM).″Bond bond(146，235)/gene＝″MBL1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Bond bond(213，227)/gene＝″MBL1″/bond_type＝″disulfide″/note＝″BY SIMILARITY″ORIGIN 1 mlllpllpvl lcvvsvsssg sqtcedtlkt csviacgrdg rdgpkgekge pgqglrglqg61 ppgklgppgs vgspgspgpk gqkgdhgdnr aieeklanme aeirilkskl qltnklhafs121 mgkksgkklf vtnhekmpfs kvkslctelq gtvaiprnae enkaiqevat giaflgitde181 ategqfmyvt ggrltysnwk kdepnnhgsg edcviildng Iwndiscqas fkavcefpaSEQ ID NO69P42916 COLLECTIN-43(CL-43)gi|1168967|sp|P42916|CL43_BOVIN[1168967]FEATURES Location/Qualifiers source 1..301/organism＝″Bos taurus″/db_xref＝″taxon:9913″Protein 1..301/product＝″COLLECTIN-43″Region 29..142/region_name＝″Domain″/note＝″COLLAGEN-LIKE(G-X-Y).″Region 202.301/region_name＝″Domain″/note＝″C-TYPE LECTIN(SHORT FORM).″Bond bond(204，299)/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Bond bond(277，291)/bond_type＝″disulfide″/note＝″BY SIMILARITY.″ORIGIN 1 eemdvysekt ltdpctlvvC appadslrgh dgrdgkegpq gekgdpgppg mpgpagregp61 sgrqgsmgpp gtpgpkgepg peggvgapgm pgspgpaglk gergapgpgg aigpqgpsga121 mgppglkgdr gdpgekgarg etsvlevdtl rqrmrnlege vqrlqnivtq yrkavlfpdg
181 qavgekifkt agavksysda eqlcreakgq lasprssaen eavtqlvrak nkhaylsmnd241 iskegkftyp tggsldysnw apgepgnrak degpenclei ysdgnwndie creerlvice301 fSEQ ID NO70CAB56155 DMBT1/8kb.2 protein[Homo sapiens]gi|5912464|emb|CAB56155.1|[5912464]sig_peptide 1..26mat_peptide 26..2412/product＝″DMBT 1/8kb.2 protein″CDS 1..2412/gene＝″DMBT1″/coded_by＝″AJ243212.1:107..7345″/note＝″Sequence is analternative splice form of the DMBT1 gene that is expressed in human adult trachea.lsoformsof DMBT1 are identical to the collectin binding protein gp-340.Full-length cDNA clonecontains 1 bp deletions in codons 100 and 1751，that were corrected by comparison with thegenomic exons″ORIGIN 1 mgistvilem cllwgqvlst ggwiprttdy aslipsevpl dttvaegspf pseltlestv61 aegspisles tlettvaegs lipsestles tvaegsdsgl alrlvngdgr cqgrveilyr121 gswgavcdds wdtndanvvc rqlgcgwams apgnawfgqg sgpialddvr csghesylws181 cphngwlshn cghgedagvi csaaqpqstl rpeswpvris ppvptegses slalrlvngg241 drcrgrvevl yrgswgtvcd dywdtndanv vcrqlgcgwa msapgnaqfg qgsgpivldd301 vrcsghesyl wscphngwlt hncghsedag vicsapqsrp tpspdtwpts hastagpess361 lalrlvnggd rcqgrvevly rgswgtvcdd swdtsdanvv crqlgcgwat sapgnarfgq421 gsgpivlddv rcsgyesylw scphngwlsh ncqhsedagv icsaahswst pspdtlptit481 lpastvgses slalrlvngg drcqgrvevl yrgswgtvcd dswdtndanv vcrqlgcgwa541 mlapgnarfg qgsgpivldd vrcsgnesyl wscphngwls hncghsedag vicsgpessl601 alrlvnggdr cqgrvevlyr gswgtvcdds wdtndanvvc rqlgcgwams apgnarfgqg661 sgpivlddvr csghesylws cpnngwlshn cghhedagvi csaaqsrstp rpdtlstitl721 ppstvgsess ltlrlvngsd rcqgrvevly rgswgtvcdd swdtndanvv crqlgcgwat781 sapgnarfgq gsgpivlddv rcsghesylw scphngwlsh ncghhedagv icsvsqsrpt841 pspdtwptsh astagpessl alrlvnggdr cqgrvevlyr gswgtvcdds wdtsdanvvc901 rqlgcgwats apgnarfgqg sgpivlddvr csgyesylws cphngwlshn cqhsedagvi961 csaahswstp spdtlptitl pastvgsess lalrlvnggd rcqgrvevly qgswgtvcdd1021 swdtndanvv crqlgcgwam sapgnarfgq gsgpivldda rcsghesylw scphngwlsh1081 ncghsedagv icsasqsrpt pspdtwptsh astagsessl airlvnggdr cqgrvevlyr1141 gswgtvcddy wdtndanvac rqlgcgwams apgnarfgqg sgpivlddvr csghesylws1201 cphngwlshn cghhedagvi csasqsqptp spdtwptsha stagsessla lrlvnggdrc1261 qgrvevlyrg swgtvcddyw dtndanvvcr qlgcgwatsa Pgnarfgqgs gpivlddvrc1321 sghesylwsc phngwlshnc ghhedagvic sasqsqptps pdtwptshas tagsesslal1381 rlvnggdrcq grvevlyrgs wgtvcddywd tndanvvcrq lgcgwatsap gnarfgqgsg1441 pivlddvrcs ghesylwscp hngwlshncg hhedagvics afqsqptpsp dtwptsrast1501 agsestlalr lvnggdrcrg rvevlyqgsw gtvcddywdt ndanvvcrql gcgwamsapg1561 naqfgqgsgp ivlddvrcsg hepylwscph ngwlshncgh hedagvicsa aqsqstprpd1621 twlttnlpal tvgsesslal rlvnggdrcr grvevlyrgs wgtvcddswd tndanvvcrq1681 lgcgwamsap gnarfgqgsg pivlgdvrcs gnesylwscp hkgwlthncg hhedagvics1741 atqinstttd wwhpttttta rpssncggfl fyasgtfssp sypayypnna kcvweievns1801 gyrinlgfsn lkleahhncs fdyveifdgs lnsslllgki cndtrqifts synrmtihfr1861 sdisfqntgf lawynsfpsd atlrlvnlns syglcagrve iyhggtwgav cddswtiqea1921 evvcrqlgcg ravsalgnay fgsgsgpitl ddvecsgtes tlwqcrnrgw fshncnhred1981 agvicsgnhl stpapflnit rpnnyscggf lsqpsgdfss Pfypgnypnn akcvwdievq2041 nnyrvtvifr dvqleggcny dyievfdgpy rsspliarvc dgargsftss snfmsirfis2101 dhsitrrgfr aeyysspsnd stnllclpnh mqasvsrsyl qslgfsasdl vistwngyye2161 crpqitpnlv iftipysgcg tfkqadndti dysnlltaav sggiikrrtd lrihvscrml2221 qntwvdtmyi andtihvann tiqveevqyg nfdvnisfyt sssflypvts rpyyvdlnqd2281 lyvqaeilhs davltlfvdt cvaspysndf tsltydlirs gcvrddtygp ysspslriar2341 frfrafhfln rfpsvylrck mvvcraydps srcyrgcvlr skrdvgsyqe kvdvvlgpiq2401 lqtpprreee prSEQ ID NO71BAA81747 collectin 34[Homo sapiens]gi|5162875|dbj|BAA81747.1|[5162875]FEATURES Location/Qualifiers source 1..277/organism＝″Homosapiens″/db_xref＝″taxon:9606″Protein 1..277/product＝″collectin 34″CDS 1..277/coded_by＝″AB002631.1:6..839″ORIGIN 1 mngfasllrr nqfillvlfl lqiqslgldi dsrptaevca thtispgpkg ddgekgdpge61 egkhgkvgrm gpkgikgelg dmgdrgnigk tgpigkkgdk gekgllgipg ekgkagtvcd121 cgryrkfvgq ldisiarlkt smkfvknvia gireteekfy yivqeeknyr eslthcrirg181 gmlampkdea antliadyva ksgffrvfig vndleregqy mftdntplqn ysnwnegeps241 dpyghedcve mlssgrwndt echltmyfvc efikkkkSEQ ID NO72AAB94071 mannan-binding lectin；collectin[Gallus gallus]gi|2736145|gb|AAB94071.1|[2736145]FEATURES Location/Qualifiers source 1..238/organism＝″Gallus gallus″/strain＝″WhiteLeghorn″/db_xref＝″taxon:9031″/tissue_type＝″liver″Protein 1..＞238/product＝″mannan-binding lectin″/name＝″c-typelectin″/note＝″mannan-binding protein；MBP；mannose-binding protein；MBL；collectin″CDS 1..238/gene＝″cMBI″/coded_by＝″AF022226.1:1..＞714″ORIGIN 1 mmatsllttd kpeekmyscp iiqcsapavn glpgrdgrdg pkgekgdpge glrglqglpg61 kagpqglkge vgpqgekgqk gergivvtdd lhrqitdlea kirvleddls rykkalslkd121 vvnigkkmfv stgkkynfek gkslcakags vlasprneae ntalkdlidp ssqayigisd181 aqtegrfmyl sggpltysnw kpgepnnhkn edcaviedsg kwndldcsns nifiicelSEQ ID NO73AAB36019 mannan-binding protein，MBP＝lectin{N-terminal}[chickens，serum，Peptide Partial，30 aa][Gallus gallus]gi|1311692|gb|AAB36019.1|[1311692]FEATURES Location/Qualifiers source 1..30/organism＝″Gallus gallus″/db_xref＝″taxon:9031″Protein 1..30/partial/product＝″mannan-binding protein″/name＝″lectin″/note＝″MBP″ORIGIN 1 lltcdkpeek myscpiiqcs apavnglpgdSEQ ID NO74AAB27504 conglutinin(N){N-terminal}[cattle，Peptide Partial，60 aa][Bos taurus]gi|386660|gb|AAB27504.1|[386660]FEATURES Location/Qualifiers source 1..60/organism＝″Bos taurus″/db_xref＝″taxon:9913″Protein 1..60/partial/product＝″conglutinin(N)″ORIGIN 1 aemttfsqki lanactlvmc splesglpgh dgqdgrecph gekgdpgspg pagragrpgwSEQ ID NO75CAA53511 collectin-43[Bos taurus]gi|499385|emb|CAA53511.1|[499385]FEATURES Location/Qualifiers source 1..301/organism＝″Bostaurus″/db_xref＝″taxon:9913″/tissue_type＝″liver″/clone_lib＝″lambda gt 11″Protein 1..301/product＝″collectin-43″mat peptide 1..301/product＝″collectin-43″CDS 1..301/coded_by＝″X75912.1:＜1..906″/db_xref＝″SWISS-PROT:P42916″ORIGIIN 1 eemdvyxekt ltdpctlvvc appadslrgh dgrdgkegpq gekgdpgppg mpgpagregp61 sgrqgsmgpp gtpgpkgepg peggvgapgm pgspgpaglk gergapgpgg aigpqgpsga121 mgppglkgdr gdpgekgarg etsvlevdtl rqrmrnlege vqrlqnivtq yrkavlfpdg181 qavgekifkt agavksysda eqlcreakgq lasprssaen eavtqlvrak nkhaylsmnd241 iskegkftyp tggsldysnw apgepgnrak degpenclei ysdgnwndie creerlvice301 fSEQ ID NO76AAA82010 mannose-binding protein C[Mus musculus]gi|773288|gb|AAA82010.1|[773288]FEATURES Location/Qualifiers source 1..244/organism＝″Musmusculus″/strain＝″BALB/c″/db_xref＝″taxon:10090″/clone＝″Lambda 14 and 52；Cos11A″/clone_lib＝″NIH/3T3 Swiss mouse embryo cell line and BALB/c pWE15 cosmidlibray″Protein 1..244/product＝″mannose-binding protein C″Site 1..59/site_type＝″signal-peptide″/note＝″signal-peptide and collagen-like region″mat_peptide<59..>98/product＝″mannose-binding protein C″/note＝″collagen-like domain″mat_peptide<98..>121/product＝″mannose-binding protein C″/note＝″linking-peptide domain″mat_peptide<121..244/product＝″carbohydrate recognition domain″CDS 1..244/gene＝″Mbl2″/coded_by＝″join(U09013.1:470..644，U09014.1:43..159，U09015.1:97..165，U09016.1:576..949)″ORIGIN 1 msiftsflll cvvtvvyaet ltegvqnscp vvtcsspgln gfpgkdgrdg akgekgepgq61 glrglqgppg kvgptgppgn pglkgavgpk gdrgdraefd tseidseiaa lrselralrn121 wvlfslsekv gkkyfvssvk kmsldnvkal csefqgsvat prnaeensai qkvakdiayl181 gitdvrvegs fedltgnrvr ytnwndgepn ntgdgedcvv ilgngkwndv pcsdsflaic241 efsdSEQ ID NO77AAA82009 mannose-binding protein A[Mus musculus]gi|773280|gb|AAA82009.1|[773280]sig_peptide 1..18mat_peptide 19..239/product＝″unnamed″mat_peptide 19..＞52/product＝″mannose-binding protein A″/note＝″collage-like region″mat_peptide<52..>91/product＝″mannose-binding protein A″/note＝″collagen-like domain″mat_peptide<91..>116/product＝″mannose-binding protein A″/note＝″linking-peptide domain″CDS 1..239/gene＝″Mbl1″/coded_by＝″join(U09007.1:275..428，U09008.1:287..403，U09009.1:166..240，U09010.1:78..451)″ORIGIN 1 mlllpllpvl lcvvsvsssg sqtcedtlkt csviacgrdg rdgpkgekge pgqglrglqg61 ppgklgppgs vgspgspgpk gqkgdhgdnr aieeklanme aeirilkskl qltnklhafs121 mgkksgkklf vtnhekmpfs kvkslctelq gtvaiprnae enkaiqevat giaflgitde181 ategqfmyvt ggrltysnwk kdepnnhgsg edcviildng lwndiscqas fkavcefpaLung surfactant proteinSEQ ID NO78P35247 Pulmonary surfactant-associated protein D precursor(SP-D)(PSP-D)gi|464486|sp|P35247|PSPD_HUMAN[464486]FEATURES Location/Qualifiers source 1..375/organism＝″Homosapiens″/db_xref＝″taxon:9606″gene 1..375/gene＝″SFTPD″/note＝″SFTP4；PSPD″Protein 1..375/gene＝″SFTPD″/product＝″Pulmonary surfactant-associated protein Dprecursor″Region 1..20/gene＝″SFTPD″/region_name＝″Signal″/note＝″BY SIMILARITY.″Region 21..375/gene＝″SFTPD″/region_name＝″Mature chain″/note＝″PULMONARYSURFACTANT-ASSOCIATED PROTEIN D.″Region 31/gene＝″SFTPD″/region_name＝″Conflict″/note＝″M-＞T(IN REF.2).″Region 46..222/gene＝″SFTPD″/region_name＝″Domain″/note＝″COLLAGEN-LIKE.″Region 59/gene＝″SFTPD″/region_name＝″Conflict″/note＝″P-＞F(IN REF.3).″Site 78/gene＝″SFTPD″/site_type＝″hydroxylation″/note＝″(BY SIMILARITY).″Site 87/gene＝″SFTPD″/site_type＝″hydroxylation″/note＝″(BY SIMILARITY).″Site 90/gene＝″SFTPD″/site_type＝″glycosylation″/note＝″N-LINKED(GLCNAC...)(POTENTIAL).″Site 96/gene＝″SFTPD″/site_type＝″hydroxylation″/note＝″(BY SIMILARITY).″Site 99/gene＝″SFTPD″/site_type＝″hydroxylation″/note＝″(BY SIMILARITY).″Region 122/gere＝″SFTPD″/region_name＝″Conflict″/note＝″A-＞P(IN REF.2).″Site 171/gene＝″SFTPD″/site_type＝″hydroxylation″/note＝″(BY SIMILARITY).″Site 177/gene＝″SFTPD″/site_type＝″hydroxylation″/note＝″(BY SIMILARITY).″Region 180/gene＝″SFTPD″/region_name＝″Conflict″/note＝″T-＞A(IN REF.2).″Region 206/gene＝″SFTPD″/region_name＝″Conflict″/note＝″D-＞P(IN REF.3).″Region 223..252/gene＝″SFTPD″/region_name＝″Domain″/note＝″COILED COIL(POTENTIAL).″Region 227..253/gene＝″SFTPD″/region_name＝″Helical region″Region 254..256/gene＝″SFTPD″/region_name＝″Hydrogen bonded turn″Region 257..260/gene＝″SFTPD″/region_name＝″Beta-strand region″Region 261..262/gene＝″SFTPD″/region_name＝″Hydrogen bonded turn″Region 263..272/gene＝″SFTPD″/region_name＝″Beta-strand region″Region 274..283/gene＝″SFTPD″/region_name＝″Helical region″Region 279..375/gene＝″SFTPD″/region_name＝″Domain″/note＝″C-TYPE LECTIN(SHORTFORM).″Bond bond(281，373)/gene＝″SFTPD″/bond_type＝″disulfide″Region 284..285/gene＝″SFTPD″/region_name＝″Hydrogen bonded turn″Region 287..288/gene＝″SFTPD″/region_name＝″Beta-strand region″Region 294..307/gene＝″SFTPD″/region_name＝″Helical region″Region 308/gene＝″SFTPD″/region_name＝″Hydrogen bonded turn″Region 311..316/gene＝″SFTPD″/region_name＝″Beta-strand region″Region 321..322/gene＝″SFTPD″/region_name＝″Hydrogen bonded turn″Region 325/gene＝″SFTPD″/region_name＝″Beta-strand region″Region 327..328/gene＝″SFTPD″/region_name＝″Hydrogen bonded turn″Region 331/gene＝″SFTPD″/region_name＝″Beta-strand region″Region 337/gene＝″SFTPD″/region_name＝″Beta-strand region″Region 339..340/gene＝″SFTPD″/region_name＝″Hydrogen bonded turn″Region 345..347/gene＝″SFTPD″/region_name＝″Helical region″Bond bond(351，365)/gene＝″SFTPD″/bond_type＝″disulfide″Region 351..354/gene＝″SFTPD″/region_name＝″Beta-strand region″Region 356..357/gene＝″SFTPD″/region_name＝″Hydrogen boded turn″Region 360..363/gene＝″SFTPD″/region_name＝″Beta-strand region″Region 365..366/gene＝″SFTPD″/region_name＝″Hydrogen bonded turn″Region 369..375/gene＝″SFTPD″/region_name＝″Beta-strand region″Region 374/gene＝″SFTPD″/region_name＝″Conflict″/note＝″E-＞EH(IN REF.3).″ORIGIN 1 mllfllsalv lltqplgyle aemktyshrt mpsactlvmc ssvesglpgr dgrdgregpr61 gekgdpglpg aagqagmpgq agpvgpkgdn gsvgepgpkg dtgpsgppgp pgvpgpagre121 galgkqgnig pqgkpgpkge agpkgevgap gmqgsagarg lagpkgergv pgergvpgnt181 gaagsagamg pqgspgargp pglkgdkgip gdkgakgesg lpdvaslrqq vealqgqvqh241 lqaafsqykk velfpngqsv gekifktagf vkpfteaqll ctqaggqlas prsaaenaal301 qqlvvaknee aflsmtdskt egkftyptge slvysnwapg epnddggsed cveiftngkw361 ndracgekrl vvcefSEQ ID NO79NP_002395 microfibrillar-associated protein 4；microfibril-associated glycoprotein 4[Homosapiens]gi|23111005|ref|NP_002395.1|[23111005]FEATURES Location/Qualifiers source 1..255/organism＝″Homosapiens″/db_xref＝″taxon:9606″/chromosome＝″17″/map＝″17p11.2″Protein 1..255/product＝″microfibrillar-associated protein 4″/note＝″microfibril-associatedglycoprotein 4″Region 36..255/region_name＝″smart00186，F(xiàn)BG，F(xiàn)ibrinogen-related domains(FReDs)；Domain present at the C-termini of fibrinogen beta and gamma chains，and a variety offibrinogen-related proteins，including tenascin and Drosophila scabrous″Region 38..254/region_name＝″pfam00147，fibrinogen_C，F(xiàn)ibrinogen beta and gamma chains，C-terminal globular domain″CDS1..255/gene＝″MFAP4″/coded_by＝″NM_002404.1:26..793″/db_xref＝″LocusID:4239″/db_xref＝″MIM:600596″ORIGIN 1 mkallalpll lllstppcap qvsgirgdal erfclqqpld cddiyaqgyq sdgvyliyps61 gpsvpvpvfc dmtteggkwt vfqkrfngsv sffrgwndyk lgfgradgey wlglqnmhll
121 tlkqkyelrv dledfennta yakyadfsis pnavsaeedg ytlfvagfed ggagdslsyh181 sgqkfstfdr dqdlfvqhca alssgafwfr schfanlngf ylggshlsya nginwaqwkg241 fyyslkrtem kirraSEQ ID NO801KMRA Chain A，Solution Nmr Structure Of Surfactant Protein B(11-25)(Sp-B11-25)gi|22219056|pdb|1KMR|A[22219056]FEATURES Location/Qualifiers source 1..15/organism＝″Homosapiens″/db_xref＝″taxon:9606″SecStr 3..11/sec_str_type＝″helix″/note＝″helix 1″ORIGIN 1 cralikriqa mipkgSEQ ID NO81P50404 Pulmonary surfactant-associated protein D precursor(SP-D)(PSP-D)gi|1709879|sp|P50404|PSPD_MOUSE[1709879]FEATURES Location/Qualifiers source 1..374/organism＝″Musmusculus″/db_xref＝″taxon:10090″gene 1..374/gene＝″SFTPD″/note＝″SFTP4″Protein 1..374/gene＝″SFTPD″/product＝″Pulmonary surfactant-associated protein Dprecursor″Region 1..19/gene＝″SFTPD″/region_name＝″Signal″/note＝″BY SIMILARITY.″Region 20..374/gene＝″SFTPD″/region_name＝″Mature chain″/note＝″PULMONARYSURFACTANT-ASSOCATED PROTEIN D.″Region 45..221/gene＝″SFTPD″/region_name＝″Domain″/note＝″COLLAGEN-LIKE.″Site 89/gene＝″SFTPD″/site_type＝″glycosylation″/note＝″N-LINKED(GLCNAC...)(POTENTIAL).″Region 222..253/gene＝″SFTPD″/region_name＝″Domain″/note＝″COILED COIL(POTENTIAL).″Region 278..374/gene＝″SFTPD″/region_name＝″Domain″/note＝″C-TYPE LECTIN(SHORTFORM).″Bond bond(280，372)/gene＝″SFTPD″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Bond bond(350，364)/gene＝″SFTPD″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″ORIGIN 1 mlpflsmlvl lvqplgnlga emkslsqrsv pntctlvmcs ptenglpgrd grdgregprg61 ekgdpglpgp mglsglqgpt gpvgpkgeng sagepgpkge rglsgppglp gipgpagkeg121 psgkqgnigp qgkpgpkgea gpkgevgapg mqgstgakgs tgpkgergap gvqgapgnag181 aagpagpagp qgapgsrgpp glkgdrgvpg drgikgesgl pdsaalrqqm ealkgklqrl241 evafshyqka alfpdgrsvg dkifrtadse kpfedaqemc kqaggqlasp rsatenaaiq301 qlitahnkaa flsmtdvgte gkftyptgep lvysnwapge pnnnggaenc veiftngqwn361 dkacgeqrlv icefSEQ ID NO82P06908 Pulmonary surfactant-associated protein A precursor(SP-A)(PSP-A)(PSAP)gi|1172693|sp|P06908|PSPA_CANFA[1172693]FEATURES Location/Qualifiers source 1..248/organism＝″Canisfamiliaris″/db_xref＝″taxon:9615″gene 1..248/gene＝″SFTPA1″/note＝″SFTPA；SFTP1″Protein 1..248/gene＝″SFTPA1″/product＝″Pulmonary surfactant-associated protein Aprecursor″Region 1..17/gene＝″SFTPA1″/region_name＝″Signal″Region 18..248/gene＝″SFTPA1″/region_name＝″Mature chain″/note＝″PULMONARYSURFACTANT-ASSOCIATED PROTEINA.″Site 20/gene＝″SFTPA1″/site_type＝″glycosylation″/note＝″N-LINKED(GLCNAC...)(POTENTIAL).″Region 28..100/gene＝″SFTPA1″/region_name＝″Domain″/note＝″COLLAGEN-LIKE.″Region 153..248/gene＝″SFTPA1″/region_name＝″Domain″/note＝″C-TYPE LECTIN(SHORTFORM).″Bond bond(155，246)/gene＝″SFTPA1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Site 207/gene＝″SFTPA1″/site_type＝″glycosylation″/note＝″N-LINKED(GLCNAC...)(PROBABLE).″Bond bond(224，238)/gene＝″SFTPA1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″ORIGIN 1 mwlrclalal tllmvsgien ntkdvcvgnp gipgtpgshg lpgrdgrdgv kgdpgppgpl61 gppggmpghp gpngmtgapg vagergekge pgergppglp asldeelqtt lhdlrhqilq121 tmgvlslhes llvvgrkvfs snaqsinfnd iqelcagagg qiaapmspee neavasivkk181 yntyaylglv espdsgdfqy mdgapvnytn wypgeprgrg keqcvemytd gqwnnknclq241 yrlaicefSEQ ID NO83P12842 Pulmonary surfactant-associated protein A precursor(SP-A)(PSP-A)(PSAP)gi|131413|sp|P12842|PSPA_RABIT[131413]FEATURES Location/Qualifiers source 1..247/organism＝″Oryctolaguscuniculus″/db_xref＝″taxon:9986″gene 1..247/gene＝″SFTPA1″/note＝″SFTPA；SFTP1″Protein 1..247/gene＝″SFTPA1″/product＝″Pulmonary surfactant-associated protein Aprecursor″Region 1..15/gene＝″SFTPA1″/region_name＝″Signal″/note＝″POTENTIAL.″Region 12/gene＝″SFTPA1″/region_name＝″Variant″/note＝″S-＞P.″Region 16..247/gene＝″SFTPA1″/region_name＝″Mature chain″/note＝″PULMONARYSURFACTANT-ASSOCIATED PROTEIN A.″Region 27..99/gene＝″SFTPA1″/region_name＝″Domain″/note＝″COLLAGEN-LIKE.″Region 57..60/gene＝″SFTPA1″/region_name＝″Conflict″/note＝″GPMG-＞APWA(IN REF.2).″Region 152..247/gene＝″SFTPA1″/region_name＝″Domain″/note＝″C-TYPE LECTIN(SHORTFORM).″Bond bond(154，245)/gene＝″SFTPA1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Site 206/gene＝″SFTPA1″/site_type＝″glycosylation″/note＝″N-LINKED(GLCNAC...)(PROBABLE).″Bond bond(223，237)/gene＝″SFTPA1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″ORIGIN 1 mlllslaltl isapasdtcd tkdvcigspg ipgtpgshgl pgrdgrdgvk gdpgppgpmg61 ppggmpglpg rdgligapgv pgergdkgep gergpPglpa yldeelqatl helrhhalqs121 igvlslqgsm kavgekifst ngqsvnfdai revcaraggr iavprsleen eaiasivker181 ntyaylglae gptagdfyyl dgdpvnytnw ypgeprgqgr ekcvemytdg kwndknclqy241 rlvicefSEQ ID NO84NP_033186 surfactant associated protein D[Mus musculus]gi|6677921|ref|NP_033186.1|[6677921]sig_peptide 1..19mat_peptide 20..374/product＝″surfactant associated protein D″Region 260..373/region_name＝″C-type lectin(CTL)or carbohydrate-recognition domain(CRD)″/note＝″CLECT″/db_xref＝″CDD:smart00034″Region 271..374/region_name＝″Lectin C-typedomain″/note＝″lectin_c″/db_xref＝″CDD:pfam00059″CDS1..374/gene＝″Sftpd″/coded_by＝″NM_009160.1:43..1167″/db_xref＝″LocusID:20390″/db_xref＝″MGD:109515″ORIGIN 1 mlpflsmlvl lvqplgnlga emkslsqrsv pntctlvmcs ptenglpgrd grdgregprg61 ekgdpglpgp mglsglqgpt gpvgpkgeng sagepgpkge rglsgppglp gipgpagkeg121 psgkqgnigp qgkpgpkgea gpkgevgapg mqgstgakgs tgpkgergap gvqgapgnag181 aagpagpagp qgapgsrgpp glkgdrgvpg drgikgesgl pdsaalrqqm ealkgklqrl241 evafshyqka alfpdgrsvg dkifrtadse kpfedaqemc kqaggqlasp rsatenaaiq
301 qlitahnkaa flsmtdvgte gkftyptgep lvysnwapge pnnnggaenc veiftngqwn361 dkacgeqrlv icefSEQ ID NO851B08C Chain C，Lung Surfactant Protein D(Sp-D)(Fragment)gi|6573321|pdb|1B08|C[6573321]FEATURES Location/Qualifiers source 1..158/organism＝″Homosapiens″/db_xref＝″taxon:9606″SecStr 13..36/sec_str_type＝″helix″/note＝″helix 7″Region 38..158/region_name＝″Domain 3″/note＝″NCBI Domains″SecStr 39..44/sec_str_type＝″sheet″/note＝″strand 21″SecStr 45..51/sec_str_type＝″sheet″/note＝″strand 22″SecStr 53..56/sec_str_tvpe＝″sheet″/note＝″strand 23″SecStr 57..67/sec_str_type＝″helix″/note＝″helix 8″Bond bond(64，156)/bond_type＝″disulfide″SecStr 77..90/sec_str_type＝″helix″/note＝″helix 9″SecStr 93..96/sec_str_type＝″sheet″/note＝″strand 24″Het join(bond(100)，bond(100)，bond(100)，bond(104)，bond(104)，bond(104)，bond(127)，bond(132)，bond(133))/heterogen＝″(CA，8)″Het join(bond(104)，bond(133)，bond(133)，bond(133))/heterogen＝″(CA，9)″SecStr 107..110/sec_str_type＝″sheet″/note＝″strand 25″SecStr 112..115/sec_str_type＝″sheet″/note＝″strand 26″Het join(bond(124)，bond(126)，bond(132)，bond(144)，bond(145)，bond(145)，bond(145)，bond(145)，bond(145)，bond(145)，bond(145)，bond(145)，bond(145)，bond(145)，bond(145)，bond(145)，bond(145)，bond(145)，bond(145)，bond(145)，bond(145)，bond(145)，bond(145)，bond(145)，bond(145)，bond(145))/heterogen＝″(CA，7)″SecStr 133..139/sec_str_type＝″sheet″/note＝″strand 27″Bond bond(134，148)/bond_type＝″disulfide″SecStr 141..147/sec_str_type＝″sheet″/note＝″strand 28″SecStr 150..158/sec_str_type＝″sheet″/note＝″strand 29″ORIGIN 1 eaeagsvasl rqqvealqgq vqhlqaafsq ykkvelfpng qsvgekifkt agfvkpftea61 qllctqaggq lasprsaaen aalqqlvvak neaaflsmtd sktegkftyp tgeslvysnw121 apgepnddgg sedcveiftn gkwndracge krlvvcefSEQ ID NO861B08B Chain B，Lung Surfactant Protein D(Sp-D)(Fragment)gi|6573320|pdb|1B08|B[6573320]FEATURES Location/Qualifiers source 1..158/organism＝″Homosapiens″/db_xref＝″taxon:9606″SecStr 11..34/sec_str_type＝″helix″/note＝″helix 4″Region 37..158/region_name＝″Domain 2″/note＝″NCBI Domains″SecStr 39..44/sec_str_type＝″sheet″/note＝″strand 11″SecStr 45..51/sec_str_type＝″sheet″/note＝″strand 12″SecStr 53..56/sec_str_type＝″sheet″/note＝″strand 13″SecStr 57..67/sec_str_type＝″helix″/note＝″helix 5″Bond bond(64，156)/bond_type＝″disulfide″SecStr 77..90/sec_str_type＝″helix″/note＝″helix 6″SecStr 93..96/sec_str_type＝″sheet″/note＝″strand 14″SecStr 97..100/sec_str_type＝″sheet″/note＝″strand 15″Het join(bond(100)，bond(100)，bond(100)，bond(104)，bond(104)，bond(104)，bond(127)，bond(132)，bond(133))/heterogen＝″(CA，5)″Het join(bond(104)，bond(133)，bond(133)，bond(133))/heterogen＝″(CA，6)″SecStr 107..110/sec_str_type＝″sheet″/note＝″strand 16″Het join(bond(124)，bond(126)，bond(132)，bond(144)，bond(145)，bond(145))/heterogen＝″(CA，4)″SecStr 133..139/sec_str_type＝″sheet″/note＝″strand 17″Bond bond(134，148)/bond_type＝″disulfide″SecStr 141..147/sec_str_type＝″sheet″/note＝″strand 18″SecStr 150..153/sec_str_type＝″sheet″/note＝″strand 19″SecStr 154..158/sec_str_type＝″sheet″/note＝″strand 20″ORIGIN 1 eaeagsvasl rqqvealqgq vqhlqaafsq ykkvelfpng qsvgekifkt agfvkpftea61 qllctqaggq lasprsaaen aalqqlvvak neaaflsmtd sktegkftyp tgeslvysnw121 apgepnddgg sedcveiftn gkwndracge krlvvcefSEQ ID NO871B08A Chain A，Lung Surfactant Protein D(Sp-D)(Fragment)gi|6573319|pdb|1B08|A[6573319]FEATURES Location/Qualifiers source 1..158/organism＝″Homosapiens″/db_xref＝″taxon:9606″SecStr 10..36/sec_str_type＝″helix″/note＝″helix 1″Region 38..158/region_name＝″Domain 1″/note＝″NCBI Domains″SecStr 39..44/sec_str_type＝″sheet″/note＝″strand 1″SecStr 45..51/sec_str_type＝″sheet″/note＝″strand 2″SecStr 53..56/sec_str_type＝″sheet″/note＝″strand 3″SecStr 57..67/sec_str_type＝″helix″/note＝″helix 2″Bond bond(64，156)/bond_type＝″disulfide″SecStr 77..90/sec_str_type＝″helix″/note＝″helix 3″SecStr 93..96/sec_str_type＝″sheet″/note＝″strand 4″SecStr 97..100/sec_str_type＝″sheet″/note＝″strand 5″Het join(bond(100)，bond(100)，bond(100)，bond(104)，bond(104)，bond(104)，bond(127)，bond(132)，bond(133))/heterogen＝″(CA，2)″Het join(bond(104)，bond(133)，bond(133)，bond(133))/heterocen＝″(CA，3)″SecStr 107..110/sec_str_type＝″sheet″/note＝″strand 6″Het join(bond(124)，bond(126)，bond(132)，bond(144)，bond(145)，bond(145))/heterogen＝″(CA，1)″SecStr 133..139/sec_str_type＝″sheet″/note＝″strand 7″Bond bond(134，148)/bond_type＝″disulfide″SecStr 141..147/sec_str_type＝″sheet″/note＝″strand 8″SecStr 150..153/sec_str_type＝″sheet″/note＝″strard 9″SecStr 154..158/sec_str_type＝″sheet″/note＝″strand 10″ORIGIN 1 eaeagsvasl rqqvealqgq vqhlqaafsq ykkvelfpng qsvgekifkt agfvkpftea61 qllctqaggq lasprsaaen aalqqlvvak neaaflsmtd sktegkftyp tgeslvysnw121 apgepnddgg sedcveiftn gkwndracge krlvvcefSEQ ID NO88NP_06004g deleted in malignant brain tumors 1 isoform c precursor[Homo sapiens]gi|8923740|ref|NP_060049.1|[8923740]sig_peptide 1.25mat_peptide 26..2403/product＝″deleted in malignant brain tumors 1 isoform c″Region 102..202/region_name＝″Scavenger receptorCys-rich″/note＝″SR″/db_xref＝″CDD:SR″Region 105..202/region_name＝″Scavenger receptor cysteine-richdomain″/note＝″SRCR″/db_xref＝″CDD:pfam00530″Region 234..334/region_name＝″Scavenger receptorCys-rich″/note＝″SR″/db_xref＝″CDD:SR″Region 237..334/region_name＝″Scavenger receptor cysteine-richdomain″/note＝″SRCR″/db_xref＝″CDD:pfam00530″Region 363..463/region_name＝″Scavenger receptorCys-rich″/note＝″SR″/db_xref＝″CDD:SR″Region 366..463/region_name＝″Scavenger receptor cysteine-richdomain″/note＝″SRCR″/db_xref＝″CDD:pfam00530″Region 484..584/region_name＝″Scavenger receptorCys-rich″/note＝″SR″/db_xref＝″CDD:SR″Region 487..584/region_name＝″Scavenger receptor cysteine-richdomain″/note＝″SRCR″/db_xref＝″CDD:pfam00530″Region 594..692/region_name＝″Scavenger receptorCys-rich″/note＝″SR″/db_xref＝″CDD:SR″Region 595..692/region_name＝″Scavenger receptor cysteine-richdomain″/note＝″SRCR″/db_xref＝″CDD:pfam00530″Region 723..823/region_name＝″Scavenger receptorCys-rich″/note＝″SR″/db_xref＝″CDD:SR″Region 726..823/region_name＝″Scavenger receptor cysteine-richdomain″/note＝″SRCR″/db_xref＝″CDD:pfam00530″Region 852..952/region_name＝″Scavenger receptorCys-rich″/note＝″SR″/db_xref＝″CDD:SR″Region 855..952/region_name＝″Scavenger receptor cysteine-richdomain″/note＝″SRCR″/db_xref＝″CDD:pfam00530″Region 983..1083/region_name＝″Scavenger receptorCys-rich″/note＝″SR″/db_xref＝″CDD:SR″Region 986..1083/region_name＝″Scavenger receptor cysteine-richdomain″/note＝″SRCR″/db_xref＝″CDD:pfam00530″Region 1112..1212/region_name＝″Scavenger receptorCys-rich″/note＝″SR″/db_xref＝″CDD:SR″Region 1115..1212/region_name＝″Scavenger receptor cysteine-richdomain″/note＝″SRCR″/db_xref＝″CDD:pfam00530″Region 1241..1341/region_name＝″Scavenger receptorCys-rich″/note＝″SR″/db_xref＝″CDD:SR″Region 1244..1341/region_name＝″Scavenger receptor cysteine-richdomain″/note＝″SRCR″/db_xref＝″CDD:pfam00530″Region 1370..1470/region_name＝″Scavenger receptorCys-rich″/note＝″SR″/db_xref＝″CDD:SR″Region 1373..1470/region_name＝″Scavenger receptor cysteine-richdomain″/note＝″SRCR″/db_xref＝″CDD:pfam00530″Region 1499..1599/region_name＝″Scavenger receptorCys-rich″/note＝″SR″/db_xref＝″CDD:SR″Region 1502..1599/region_name＝″Scavenger receptor cysteine-richdomain″/note＝″SRCR″/db_xref＝″CDD:pfam00530″Region 1630..1730/region_rame＝″Scavenger receptorCys-rich″/note＝″SR″/db_xref＝″CDD:SR″Region 1633..1730/region_name＝″Scavenger receptor cysteine-richdomain″/note＝″SRCR″/db_xref＝″CDD:pfam00530″Region 1756..1867/region_name＝″Domain first found in C1r，C1s，uEGF，and bonemorphogenetic protein.″/note＝″CUB″/db_xref＝″CDD:CUB″Region 1756..1864/region_name＝″CUB domain″/note＝″CUB″/db_xref＝″CDD:pfam00431″Region 1873..1976/region_name＝″Scavenger receptorCys-rich″/note＝″SR″/db_xref＝″CDD:SR″Region 1885..1976/region_name＝″Scavenger receptor cysteine-richdomain″/note＝″SRCR″/db_xref＝″CDD:pfan00530″Region 1998..2106/region_name＝″Domain first found in C1r，C1s，uEGF，and bonemorphogenetic protein.″/note＝″CUB″/db_xref＝″CDD:CUB″Region 1998..2104/region_name＝″CUB domain″/note＝″CUB″/db_xref＝″CDD:pfam00431″Region 2117..2371/region_name＝″Zona pellucida-likedomain″/note＝″zona_pellucida″/db_xref＝″CDD:pfam00100″Region 2117..2368/region_name＝″Zona pellucida(ZP)domain″/note＝″ZP″/db_xref＝″CDD:ZP″CDS 1..2403/gene＝″DMBT1″/coded_by＝″NM_017579.1:107..7318″/note＝″isoform c isencoded by transcript varia nt 3″/db_xref＝″LocusID:1755″/db_xref＝″MIM:601969″ORIGIN 1 mgistvilem cllwgqvlst ggwiprttdy aslipsevpl dttvaegspf pseltlesta61 aegspisles tlestvaegs lipsestles tvaegsdsgl alrlvngdgr cqgrveilyr121 gswgtvcdds wdtndanvvc rqlgcgwams apgnawfgqg sgpialddvr csghesylws181 cphngwlshn cghgedagvi csaaqpqstl rpeswpvris ppvptegses slalrlvngg241 drcrgrvevl yrgswgtvcd dywdtndanv vcrqlgcgwa msapgnaqfg qgsgpivldd301 vrcsghesyl wscphngwlt hncghsedag vicsaplsrp tpspdtwpts hastagpess361 lalrlvnggd rcqgrvevly rgswgtvcdd swdtsdanvv crqlgcgwat sapgnarfgq421 gsgpivlddv rcsgyesylw scphngwlsh ncqhsedagv icsdtlptit lpastvgses481 slalrlvngg drcqgrvevl yrgswgtvcd dswdtndanv vcrqlgcgwa mlapgnarfg541 qgsgpivldd vrcsgnesyl wscphngwls hncghsedag vicsgpessl alglvnggdr601 cqgrvevlyr gswgtvcdds wdtndanvvc rqlgcgwats apgnarfgqg sgpivlddvr661 csghesylws cpnngwlshn cghhedagvi csaaqsrstp rpdtlstitl ppstvgsess721 ltlrlvngsd rcqgrvevly rgswgtvcdd swdtndanvv crqlgcgwat sapgnarfgq781 gsgpivlddv rcsghesylw scphngwlsh ncghhedagv icsvsqsrpt pspdtwptsh841 astagsessl alrlvnggdr cqgrvevlyr gswgtvcdds wdtsdanvvc rrlgcgwats901 apgnarfgqg sgpivlddvr csgyesylws cphngwlshn cqhsedagvi csaahswstp961 spdtlptitl pastvgsess lalrlvnggd rcqgrvevly qgswgtvcdd swdtndanvv1021 crqlgcgwam sapgnarfgq gsgpivlddv rcsghesylw scphngwlsh ncghsedagv1081 icsasqsrpt pspdtwptsh astagsessl alrlvnggdr cqgrvevlyr gswgtvcddy1141 wdtndanvvc rqlgcgwams apgnarfgqg sgpivlddvr csghesylws cphdgwlshn1201 cghhedagvi csasqsqptp spdtwptsha stagsassla lrlvnggdrc qgrvevlyrg1261 pwgtvcddyw dtndanvvcr qlgcgwatsa pgnarfgqgs gpivlddvrc sghesylwsc1321 phngwlshnc ghhedagvic sasqsqptps pdtwptshas tagsesslal rlvnggdrcq1381 grvevlyrgs wgtvcddywd tndanvvcrq lgcgwatsap gsarfgqgsg pialddvrcs1441 ghesylwscp hngwlshncg hhedagvics asqsqptpsp dtwptsrast agsestlalr1501 lvnggdrcrg rvevlyqgsw gtvcddywdt ndanvvcrql gcgwamsapg naqfgqgsgp1561 ivlddvrcsg hesylwscph ngwlshncgh hedagvicsa aqsqstprpd twlttnlpal1621 tvgsesslal rlvnggdrcr grvevlyrgs wgtvcddswd tndanvvcrq lgcgwamsap1681 gnarfgqgsg pivlddvrcs gnesylwscp hkgwlthncg hhedagvics atqinstttd1741 wwhpttttta rpssncggfl fyasgtfssp sypayypnna kcvweievns gyrinlgfsn1801 lkleahhncs fdyveifdgs lnsslllgki cndtrqifts synrmtihfr sdisfqntgf1861 lawynsfpsd atlrlvnlns syglcagrye iyhggtwgtv cddswtiqea evvcrqlgcg1921 ravsalgnay fgsgsgpitl ddvecsgtes tlwqcrnrgw fshncnhred agvicsgnhl1981 stpapflnit rpntdyscgg flsqpsgdfs spfypgnypn nakcvwdiev qnnyrvtvif2041 rdvqleggcn ydyievfdgp yrsspliarv cdgargsfts ssnfmsirfi sdhsitrrgf2101 iaeyysspsn dstnilclpn hmqasvsrsy lqslgfsasd lvistwngyy ecrpqitpnl2161 viftipysgc gtfkqadndt idysnfltaa vsggiikrrt dlrihvscrm lqntwvdtmy2221 iandtihvan ntiqveevqy gnfdvnisfy tsssflypvt srpyyvdlnq dlyvqaeilh2281 sdavltlfvd tcvaspysnd ftsltydlir sgcvrddtyg pysspslria rfrfrafhfl2341 nrfpsvylrc kmvvcraydp ssrcyrgcvl rskrdvgsyq ekvdvvlgpi qlqtpprree2401 eprSEQ ID NO89NP_015568 deleted in malignant brain tumors 1 isoform b precursor[Homo sapiens]gi|6633801|ref|NP_015568.1|[6633801]sig_peptide 1..25mat_peptide 26..2413/product＝″deleted in malignant brain tumors 1 isoform b″Region 102..202/region_name＝″Scavenger receptorCvs-rich″/note＝″SR″/db_xref＝″CDD:SR″Region 105..202/region_name＝″Scavenger receptor cysteine-richdomain″/note＝″SRCR″/db_xref＝″CDD:pfam00530″Region 234..334/region_name＝″Scavenger receptorCys-rich/note＝″SR″/db_xref＝″CDD:SR″Region 237..334/region_name＝″Scavenger receptor cysteine-richdomain″/note＝″SRCR″/db_xref＝″CDD:pfam00530″Region 363..463/region_name＝″Scavenger receptorCys-rich″/note＝″SR″/db_xref＝″CDD:SR″Region 366..463/region_name＝″Scavenger receptor cysteine-richdomain″/note＝″SRCR″/db_xref＝″CDD:pfam00530″Region 494..594/region_name＝″Scavenger receptorCys-rich″/note＝″SR″/db_xref＝″CDD:SR″Region 497..594/region_name＝″Scavenger receptor cysteine-richdomain″/note＝″SRCR″/db_xref＝″CDD:pfam00530″Region 602..702/region_name＝″Scavenger receptorCys-rich″/note＝″SR″/db_xref＝″CDD:SR″Region 605..702/region_name＝″Scavenger receptor cysteine-richdomain″/note＝″SRCR″/db_xref＝″CDD:pfam00530″Region 733..833/region_name＝″Scavenger receptorCys-rich″/note＝″SR″/db_xref＝″CDD:SR″Region 736..833/region_name＝″Scavenger receptor cysteine-richdomain″/note＝″SRCR″/db_xref＝″CDD:pfam00530″Region 862..962/region_name＝″Scavenger receptorCys-rich″/note＝″SR″/db_xref＝″CDD:SR″Region 865..962/region_name＝″Scavenger receptor cysteine-richdomain″/note＝″SRCR″/db_xref＝″CDD:pfam00530″Region 993..1093/region_name＝″Scavenger receptorCys-rich″/note＝″SR″/db_xref＝″CDD:SR″Region 996..1093/region_name＝″Scavenger receptor cysteine-richdomain″/note＝″SRCR″/db_xref＝″CDD:pfam00530″Region 1122..1222/region_name＝″Scavenger receptorCys-rich″/note＝″SR″/db_xref＝″CDD:SR″Region 1125..1222/region_name＝″Scavenger receptor cysteine-richdomain″/note＝″SRCR″/db_xref＝″CDD:pfam00530″Region 1251..1351/region_name＝″Scavenger receptorCys-rich″/note＝″SR″/db_xref＝″CDD:SR″Region 1254..1351/region_name＝″Scavenger receptor cysteine-richdomain″/note＝″SRCR″/db_xref＝″CDD:pfam00530″Region 1380..1480/region_name＝″Scavenger receptorCys-rich″/note＝″SR″/db_xref＝″CDD:SR″Region 1383..1480/region_name＝″Scavenger receptor cysteine-richdomain″/note＝″SRCR″/db_xref＝″CDD:pfam00530″Region 1509..1609/region_name＝″Scavenger receptorCys-ric″/note＝″SR″/db_xref＝″CDD:SR″Region 1512..1609/region_name＝″Scavenger receptor cysteine-richdomain″/note＝″SRCR″/db_xref＝″CDD:pfam00530″Region 1640..1740/region_name＝″Scavenger receptorCys-rich″/note＝″SR″/db_xref＝″CDD:SR″Region 1643..1740/region_name＝″Scavenger receptor cysteine-richdomain″/note＝″SRCR″/db_xref＝″CDD:pfam00530″Region 1766..1877/region_name＝″Domain first found in C1r，C1s，uEGF，ard bonemorphogenetic protein.″/note＝″CUB″/db_xref＝″CDD:CUB″Region 1766..1874/region_name＝″CUB domain″/note＝″CUB″/db_xref＝″CDD:pfam00431″Region 1883..1986/region_name＝″Scavenger receptorCys-rich″/note＝″SR″/db_xref＝″CDD:SR″Region 1895..1986/region_name＝″Scavenger receptor cysteine-richdomain″/note＝″SRCR″/db_xref＝″CDD:pfam00530″Region 2008..2116/region_name＝″Domain first found in C1r，C1s，uEGF，and bonemorphogenetic protein.″/note＝″CUB″/db_xref＝″CDD:CUB″Region 2008..2114/region_name＝″CUB domain″/note＝″CUB″/db_xref＝″CDD:pfam00431″Region 2127..2381/region_name＝″Zona pellucida-likedomain″/note＝″zona_pellucida″/db_xref＝″CDD:pfam00100″Region 2127..2378/region_name＝″Zona pellucida(ZP)domain″/note＝″ZP″/db_xref＝″CDD:ZP″CDS1..2413/gene＝″DMBT1″/coded_by＝″NM_007329.1:107..7348″/db_xref＝″LocusID:1755″/db_xref＝″MIM:601969″ORIGIN 1 mgistvilem cllwgqvlst ggwiprttdy aslipsevpl dqtvaegspf psestlesta61 aegspisles tlestvaegs lipsestles tvaegsdsgl alrlvngdgr cqgrveliyr121 gswgtvcdds wdtndanvvc rqlgcgwams apgnawtgqg sgpialddvr csghesylws181 cphngwlshn cghgedagvi csaaqpqstl rpeswpvris ppvptegses slalrlvngg241 drcrgrvevl yrgswgtvcd dywdtndanv vcrqlgcgwa msapgnaqfg qgsgpivldd301 vrcsghesyl wscphngwlt hncghsedag vicsapqsrp tpspdtwpts hastagpess361 lalrlvnggd rcqgrvevly rgswgtvcdd swdtsdanvv crqlgcgwat sapgnarfgq421 gsgpivlddv rcsgyesylw scphngwlsh ncqhsedagv icsaahswst pspdtlptit481 lpastvgses slalrlvngg drcqgrvevl yrgswgtvcd dswdtndanv vcrqlgcgwa541 mlapgnarfg qgsgpivldd vrcsgnesyl wscphngwls hncghsedag vicsgpessl601 alrlvnggdr cqgrvevlyr gswgtvcdds wdtndanvvc rqlgcgwams apgnarfgqg661 sgpivlddvr csghesylws cpnngwlshn cghhedagvi csaaqsrstp rpdtlstitl721 ppstvgsess ltlrlvngsd rcqgrvevly rgswgtvcdd swdtndarvv crqlgcgwam781 sapgnarfgq gsgpivlddv rcsghesylw scphngwlsh ncghhedagv icsvsqsrpt841 pspdtwptsh astagsessl alrlvnggdr cqgrvevlyr gswgtvcdds wdtsdanvvc901 rqlgcgwats apgnarfgqg sgpivlddvr csgyesylws cphngwlshn cqhsedagvi961 csaahswstp spdtlptitl pastvgsess lalrlvnggd rcqgrvevly qgswgtvcdd1021 swdtndanvv crqpgcgwam sapgnarfgq gsgpivlddv rcsghesypw scphngwlsh1081 ncghsedagv icsasqsrpt pspdtwptsh astagsessl alrlvnggdr cqgrvevlyr1141 gswgtvcddy wdtndanvvc rqlgcgwams apgnarfgqg sgpivlddvr csghesylws1201 cphngwlshn cghhedagvi csasqsqptp spdtwptsha stagsessla lrlvnggdrc1261 qgrvevlyrg swgtvcddyw dtndanvvcr qlgcgwatsa pgnarfgqgs gpivlddvrc1321 sghesylwsc phngwlshnc ghhedagvic sasqsqptps pdtwptshas tagsesslal1381 rlvnggdrcq grvevlyrgs wgtvcddywd tndanvvcrq lgcgwatsap gnarfgqgsg1441 pivlddvrcs ghesylwscp hngwlshncg hhedagvics asqsqptpsp dtwptsrast1501 agsestlalr lvnggdrcrg rvevlyqgsw gtvcddywdt ndanvvcrql gcgwamsapg1561 naqfgqgsgp ivlddvrcsg hesylwscph ngwlshncgh hedagvicsa aqsqstprpd1621 twlttnlpal tvgsesslal rlvnggdrcr grvevlyrgs wgtvcddswd tndanvvcrq1681 lgcgwamsap gnarfgqgsg pivlddvrcs gnesylwscp hkgwlthncg hhedagvics1741 atqinstttd wwhpttttta rpssncggfl fyasgtfssp sypayypnna kcvweievns1801 gyrinlgfsn lkleahhncs fdyveifdgs lnsslllgki cndtrqifts synrmtihfr1861 sdisfqntgf lawynsfpsd atlrlvnlns syglcagrve iyhggtwgtv cddswtiqea1921 evvcrqlgcg ravsalgnay fgsgsgpitl ddvecsgtes tlwqcrnrgw fshncnhred1981 agvicsgnhl stpapflnit rpntdyscgg flsqpsgdfs spfypgnypn nakcvwdiev2041 qnnyrvtvif rdvqleggcn ydyievfdgp yrsspliarv cdgargsfts ssnfmsirfi2101 sdhsitrrgf raeyysspsn dstnllclpn hmqasvsrsy lqslgfsasd lvistwngyy2161 ecrpqitpnl viftipysgc gtfkqadndt idysnfltaa vsggiikrrt dlrihvscrm2221 lqntwvdtmy iandtihvan ntiqveevqy gnfdvnisfy tsssflypvt srpyyvdlnq2281 dlyvqaeilh sdavltlfvd tcvaspysnd ftsltydlir sgcvrddtyg pysspslria2341 rfrfrafhfl nrfpsvylrc kmvvcraydp ssrcyrgcvl rskrdvgsyq ekvdvvlgpi2401 qlqtpprree eprSEQ ID NO90NP_004397 deleted in malignant brain tumors 1 isoform a precursor[Homo sapiens]gi|4758170|ref|NP_004397.1|[4758170]sig_peptide 1..25mat_peptide 26..1785/product＝″deleted in malignant brain tumors 1 isoform a″Region 102..202/region_name＝″Scavenger receptorCys-rich″/note＝″SR″/db_xref＝″CDD:SR″Region 105..202/region_name＝″Scavenger receptor cysteine-richdomain″/note＝″SRCR″/db_xref＝″CDD:pfam00530″Region 234..334/region_name＝″Scavenger receptorCys-rich″/note＝″SR″/db_xref＝″CDD:SR″Region 237..334/region_name＝″Scavenger receptor cysteine-richdomain″/note＝″SRCR″/db_xref＝″CDD:pfam00530″Region 363..463/region_name＝″Scavenger receptorCys-rich″/note＝″SR″/db_xref＝″CDD:SR″Region 366..463/region_name＝″Scavenger receptor cysteine-richdomain″/note＝″SRCR″/db_xref＝″CDD:pfam00530″Region 494..594/region_name＝″Scavenger receptorCys-rich″/note＝″SR″/db_xref＝″CDD:SR″Region 497..594/region_name＝″Scavenger receptor cysteie-richdomain″/note＝″SRCR″/db_xref＝″CDD:pfam00530″Region 623..723/region_name＝″Scavenger receptorCys-rich″/note＝″SR″/db_xref＝″CDD:SR″Region 626..723/region_name＝″Scavenger receptor cysteine-richdomain″/note＝″SRCR″/db_xref＝″CDD:pfam00530″Region 752..852/region_name＝″Scavenger receptorCys-rich″/note＝″SR″/db_xref＝″CDD:SR″Region 755..852/region_name＝″Scavenger receptor cysteine-richdomain″/note＝″SRCR″/db_xref＝″CDD:pfam00530″Region 881..981/region_name＝″Scavenger receptorCys-rich″/note＝″SR″/db_xref＝″CDD:SR″Region 884..981/region_name＝″Scavenger receptor cysteine-richdomain″/note＝″SRCR″/db_xref＝″CDD:pfam00530″Region 1012..1112/region_name＝″Scavenger receptorCys-rich″/note＝″SR″/db_xref＝″CDD:SR″Region 1015..1112/region_name＝″Scavenger receptor cysteine-richdomain″/note＝″SRCR″/db_xref＝″CDD:pfam00530″Region 1138..1249/region_name＝″Domain first found in C1r，C1s，uEGF，and bonemorphogenetic protein.″/note＝″CUB″/db_xref＝″CDD:CUB″Region 1138..1246/region_name＝″CUB domain″/note＝″CUB″/db_xref＝″CDD:pfam00431″Region 1255..1358/region_name＝″Scavenger receptorCys-rich″/note＝″SR″/db_xref＝″CDD:SR″Region 1267..1358/region_name＝″Scavenger receptor cysteine-richdomain″/note＝″SRCR″/db_xref＝″CDD:pfam00530″Region 1380..1488/region_name＝″Domain first found in C1r，C1s，uEGF，and bonemorphogenetic protein.″/note＝″CUB″/db_xref＝″CDD:CUB″Region 1380..1486/region_name＝″CUB domain″/note＝″CUB″/db_xref＝″CDD:pfam00431″Region 1499..1751/region_name＝″Zona pellucida-likedomain″/note＝″zona_pellucida″/db_xref＝″CDD:pfam00100″Region 1499..1750/region_name＝″Zona pellucida(ZP)domain″/note＝″ZP″/db_xref＝″CDD:ZP″CDS1..1785/gene＝″DMBT1″/coded_by＝″NM_004406.1:107..5464″/db_xref＝″LocusID:1755″/db_xre＝″MIM:601969″ORIGIN 1 mgistvilem cllwgqvlst ggwiprttdy aslipsevpl dqtvaegspf psestlesta61 aegspisles tlestvaegs lipsestles tvaegsdsgl alrlvngdgr cqgrveilyr121 gswgtvcdds wdtndanvvc rqlgcgwams apgnawfgqg sgpialddvr csghesylws181 cphngwlshn cghgedagvi csaaqpqstl rpeswpvris ppvptegses slalrlvngg241 drcrgrvevl yrgswgtvcd dywdtndanv vcrqlgcgwa msapgnaqfg qgsgpivldd301 vrcsghesyl wscphngwlt hncghsedag vicsapqsrp tpspdtwpts hastagpess361 lalrlvnggd rcqgrvevly rgswgtvcdd swdtsdanvv crqlgcgwat sapgnarfgq421 gsgpivlddv rcsgyesylw scphngwlsh ncqhsedagv icsaahswst pspdtlptit481 lpastvgses slalrlvngg drcqgrvevl yqgswgtvcd dswdtndanv vcrqpgcgwa541 msapgnartg qgsgpivldd vrcsghesyp wscphngwls hncghsedag vicsasqsrp601 tpspdtwpts hastagsess lalrlvnggd rcqgrvevly rgswgtvcdd ywdtndanvv661 crqlgcgwam sapgnarfgq gsgpivlddv rcsghesylw scphngwlsh ncghhedagv721 icsasqsqpt pspdtwptsh astagsessl alrlvnggdr cqgrvevlyr gswgtvcddy
781 wdtndanvvc rqlgcgwats apgnarfgqg sgpivlddvr csghesylws cphngwlshn841 cghhedagvi csasqsqptp spdtwptsra stagsestla lrlvnggdrc rgrvevlyqg901 swgtvcddyw dtndanvvcr qlgcgwamsa pgnaqfgqgs gpivlddvrc sghesylwsc961 phngwlshnc ghhedagvic saaqsqstpr pdtwlttnlp altvgsessl alrlvnggdr1021 crgrvevlyr gswgtvcdds wdtndanvvc rqlgcgwams apgnarfgqg sgpivlddvr1081 csgnesylws cphkgwlthn cghhedagvi csatqinstt tdwwhptttt tarpssncgg1141 flfyasgtfs spsypayypn nakcvweiev nsgyrinlgf snlkleahhn csfdyveifd1201 gslnsslllg kicndtrqif tssynrmtih frsdisfqnt gflawynsfp sdatlrlvnl1261 nssyglcagr veiyhggtwg tvcddswtiq eaevvcrqlg cgravsalgn ayfgsgsgpi1321 tlddvecsgt estlwqcrnr gwfshncnhr edagvicsgn hlstpapfln itrpntdysc1381 ggflsqpsgd fsspfypgny pnnakcvwdi evqnnyrvtv ifrdvqlegg cnydyievfd1441 gpyrssplia rvcdgargsf tsssnfmsir fisdhsitrr gfraeyyssp sndstnllcl1501 pnhmqasvsr sylqslgfsa sdlvistwng yyecrpqitp nlviftipys gcgtfkqadn1561 dtidysnflt aavsggiikr rtdlrihvsc rmlqntwvdt myiandtihv anntiqveev1621 qygnfdvnis fytsssflyp vtsrpyyvdl nqdlyvqaei lhsdavltlf vdtcvaspys1681 ndftsltydl irsgcvrddt ygpysspslr iarfrfrafh flnrfpsvyl rckmvvcray1741 dpssrcyrgc vlrskrdvgs yqekvdvvlg piqlqtpprr eeeprSEQ ID NO91LNBOC1 pulmonary surfactant protein C-bovine gil7428752|pir||LNBOC1[7428752]FEATURES Location/Qualifiers source 1..34/organism＝″Bos taurus″/db_xref＝″taxon:9913″Protein 1..34/product＝″pulmonary surfactant protein C″/note＝″pulmonary surfactant proteinPSP-6″Site 4/site_type＝″binding″/note＝″palmitate(Cys)(covalent)″Site 5/site_type＝″binding″/note＝″palmitate(Cys)(covalent)″ORIGIN 1 lipccpvnik rllivvvvvv llvvvivgal lmglSEQ ID NO92LNDGC1 pulmonary surfactant protein C-dog gi|7428750|pir||LNDGC1[7428750]FEATURES Location/Qualifiers source 1..35/organism＝″Canisfamiliaris″/db_xref＝″taxon:9615″Protein 1..35/product＝″pulmonary surfactant protein C″Site 5/site_type＝″binding″/note＝″palmitate(Cys)(covalent)″ORIGIN 1 lgipcfpssl krlliivvvi vlvvvvivga llmgl//SEQ ID NO93JN0450 conglutinin precursor-bovine gi|346501|pir|JN0450[346501]FEATURES Location/Qualifiers source 1..371/organism＝″Bos taurus″/db_xref＝″taxon:9913″Protein 1..371/product＝″conglutinin precursor″/note＝″C3b-binding protein″Region 1..20/region_name＝″domain″/note＝″signal sequence″Region 21..371/region_name＝″product″/note＝″conglutinin″Region 46..214/region_name＝″region″/note＝″collagen-like″Site 63/site_type＝″binding″/note＝″carbohydrate(Lys)(covalent)″Site 63/site_type＝″modified″/note＝″5-hydroxylysine(Lys)″Region 75..371/region_name＝″product″/note＝″conglutinin-N″Site 78/site_type＝″modified″/note＝″4-hydroxyproline(Pro)″Site 87/site_type＝″binding″/note＝″carbohydrate(Lys)(covalent)″Site 87/site_type＝″modified″/note＝″5-hydroxylysine(Lys)″Site 96/site_type＝″modified″/note＝″4-hydroxyproline(Pro)″Site 99/site_type＝″binding″/note＝″carbohyd rate(Lys)(covalent)″Site 99/site_type＝″modified″/note＝″5-hydroxylysine(Lys)″Site 108/site_type＝″modified″/note＝″4-hydroxyproline(Pro)″Site 111/site_type＝″modified″/note＝″4-hydroxyproline(Pro)″Site 129/site_type＝″modified″/note＝″4-hydroxyproline(Pro)″Site 132/site_type＝″modified″/note＝″4-hydroxyproline(Pro)″Site 135/site_type＝″binding″/note＝″carbohydrate(Lys)(covalent)″Site 135/site_type＝″modified″/note＝″5-hydroxylysine(Lys)″Site 141/site_type＝″binding″/note＝″carbohydrate(Lys)(covalent)″Site 141/site_type＝″modified″/note＝″5-hydroxylysine(Lys)″Site 147/site_type＝″modified″/note＝″4-hydroxyproline(Pro)″Site 153/site_type＝″modified″/note＝″4-hydroxyproline(Pro)″Site 159/site_type＝″binding″/note＝″carbohydrate(Lys)(covalent)″Site 159/site_type＝″modified″/note＝″5-hydroxylysine(Lys)″Site 162/site_type＝″binding″/note＝″carbohydrate(Lys)(covalent)″Site 162/site_type＝″modified″/note＝″5-hydroxylysine(Lys)″Site 171/site_type＝″modified″/note＝″4-hydroxyproline(Pro)″Site 195/site_type＝″modified″/note＝″4-hydroxyproline(Pro)″Site 198/site_type＝″binding″/note＝″carbohydrate(Lys)(covalent)″Site 198/site_type＝″modified″/note＝″5-hydroxylysine(Lys)″Site 210/site_type＝″binding″/note＝″carbohydrate(Lys)(covalent)″Site 210/site_type＝″modified″/note＝″5-hydroxylysine(Lys)″Region 248..369/region_name＝″domain″/note＝″C-type lectin homology#label LCH″Site 337/site_type＝″binding″/note＝″carbohydrate(Asn)(covalent)″ORIGIN 1 mlllplsvll lltqpwrslg aemttfsqki lanactlvmc splesglpgh dgqdgrecph61 gekgdpgspg pagragrpgw vgpigpkgdn gfvgepgpkg dtgprgppgm pgpagregps121 gkqgsmgppg tpgpkgetgp kggvgapgiq gfpgpsglkg ekgapgetga pgrag/tgps181 gaigpqgpsg argppglkgd rgdpgetgak gesglaevna lkqrvtildg hlrrfqnafs241 qykkavlfpd gqavgekifk tagavksysd aeqlcreakg qlasprssae neavtqmvra301 qeknaylsmn distegrfty ptgeilvysn wadgepnnsd egqpencvei fpdgkwndvp361 cskqllvice fSEQ ID NO94A45225 pulmonary surfactant protein D precursor-human gi|346375|pir||A45225[346375]FEATURES Location/Qualifiers source 1.375/organism＝″Homosapiens″/db_xref＝″taxon:9606″Protein 1..375/product＝″pulmonary surfactant protein D precursor″/note＝″SP-D″Region 1..20/region_name＝″domain″/note＝″signal sequence″Region 21..375/region_name＝″product″/note＝″pulmonary surfactant protein D″Region 21..45/region_name＝″domain″/note＝″non-collagenous″Region 46..222/region_name＝″domain″/note＝″collagenous″Site 90/site_type＝″binding″/note＝″carbohydrate(Asn)(covalent)″Region 223..375/region_name＝″domain″/note＝″non-collagenous″Region 254..373/region_name＝″domain″/note＝″C-type lectin homology#label LCH″Bond bond(281，373)/bond_type＝″disulfide″Bond bond(351，365)/bond_type＝″disulfide″ORIGIN 1 mllfllsalv lltqplgyle aemktyshrt mpsactlvmc ssvesglpgr dgrdgregpr61 gekgdpglpg aagqagmpgq agpvgpkgdn gsvgepgpkg dtgpsgppgp pgvpgpagre121 galgkqgnig pqgkpgpkge agpkgevgap gmqgsagarg lagpkgergv pgergvpgnt181 gaagsagamg pqgspgargp pglkgdkgip gdkgakgesg lpdvaslrqq vealqgqvqh241 lqaafsqykk velfpngqsv gekifktagf vkpfteaqll ctqaggqlas p rsaaenaal301 qqlwaknea aflsmtdskt egkftyptge slvysnwapg epnddggsed cveiftngkw361 ndracgekrl vvcefSEQ ID NO95LNHUC pulmonary surfactant protein C precursor，long splice form-humangi|71983|pir||LNHUC[71983]FEATURES Location/Qualifiers source 1..197/organism＝″Homosapiens″/db_xref＝″taxon:9606″Protein 1..197/product＝″pulmonary surfactant protein C precursor，long spliceform″/note＝″3.7kDa surfactant polypeptide；pulmonary surfactant protein SP5；pulmonarysurfactant proteolipid SP-C；pulmonary surfactant proteolipid SPL(pVal)″Region 1..197/region_name＝″product″/note＝″pulmonary surfactant protein C precursor，shortsplice form″Region 1..145/region_name＝″product″/note＝″pulmonary surfactant protein C precursor，shortsplice form″Region 1..23/region_name＝″domain″/note＝″propeptide″Region 24..58/region_name＝″product″/note＝″pulmonary surfactant protein C″Site 28/site_type＝″binding″/note＝″palmitate(Cys)(covalent)″Site 29/site_type＝″binding″/note＝″palmitate(Cys)(covalent)″Region 152..197/region_name＝″product″/note＝″pulmonary surfactant protein C precursor，short splice form″ORIGIN 1 mdvgskevlm esppdysaap rgrfgipccp vhlkrllivv vvvvlivvvivgallmglhm61 sqkhtemvle msigapeaqq rlalsehlvt tatfsigstg lvvydyqqll iaykpapgtc121 cyimkiapes ipslealnrk vhnfqmecsl qakpavptsk lgqaegrdag sapsggdpaf181 lgmavntlcg evplyyiSEQ ID NO96LNDGPS pulmonary surfactant protein A precursor-dog gi|71970|pir||LNDGPS[71970]FEATURES Location/Qualifiers source 1..248/organism＝″Canisfamiliaris″/db_xref＝″taxon:9615″Protein 1..248/product＝″pulmonary surfactant protein A precursor″/note＝″pulmonarysurfactant 32K apoprotein；pulmonary surfactant-associated protein PSP-A″Region 1..17/region_name＝″domain″/note＝″signal sequence″Region 18..248/region_name＝″product″/note＝″pulmonary surfactant protein A″Site 20/site_type＝″binding″/note＝″carbohydrate(Asn)(covalent)″Region 28..102/region_name＝″region″/note＝″collagen-like″Site 30/site_type＝″modified″/note＝″4-hydroxyproline(Pro)″Region 127..246/region_name＝″domain″/note＝″C-type lectin homology#label LCH″Site 207/site_type＝″binding″/note＝″carbohydrate(Asn)(covalent)″ORIGIN 1 mwlrclalal tllmvsgien ntkdvcvgnp gipgtpgshg lpgrdgrdgv kgdpgppgpl61 gppggmpghp gpngmtgapg vagergekge pgergppglp asldeelqttlhdlrhqilq121 tmgvlslhes llvvgrkvfs sgaqsinfnd iqelcagagg qiaapmspee neavasivkk181 yntyaylglv espdsgdfqy mdgapvnytn wypgeprgrg keqcvemytd gqwnnknclq241 yrlaicefSEQ ID NO97LNHUPS pulmonary surfactant protein A precursor(genomic clone)-humangi|71967|pir||LNHUPS[71967]FEATURES Location/Qua|ifiers source 1..248/organism＝″Homosapiens″/db_xref＝″taxon:9606″Protein 1..248/product＝″pulmonary surfactant protein A precursor(genomicclone)″/note＝″alveolar proteinosis protein；pulmonary surfactant 32K apoprotein；pulmonarysurfactant-associated protein(PSP-A)″Region 1..20/region_name＝″domain″/note＝″signal sequence″Region 21..248/region_name＝″product″/note＝″pulmonary surfactant protein A″Bond bond(26)/bond_type＝″disulfide″/note＝″interchain″Region 28..100/region_name＝″domain″/note＝″collagenous″Site 30/site_type＝″modified″/note＝″4-hydroxyproline(Pro)″Site 33/site_type＝″modified″/note＝″4-hydroxyproline(Pro)″Site 36/site_type＝″modified″/note＝″4-hydroxyproline(Pro)″Site 42/site_type＝″modified″/note＝″4-hydroxyproline(Pro)″Site 51/site_type＝″modified″/note＝″5-hydroxylysine(Lys)″Site 57/site_type＝″modified″/note＝″4-hydroxyproline(Pro)″Site 63/site_type＝″modified″/note＝″4-hydroxyproline(Pro)″Site 76/site_type＝″modified″/note＝″4-hydroxyproline(Pro)″Site 79/site_type＝″modified″/note＝″4-hydroxyproline(Pro)″Site 82/site_type＝″modified″/note＝″4-hydroxyproline(Pro)″Site 88/site_type＝″modified″/note＝″5-hydroxylysine(Lys)″Site 91/site_type＝″modified″/note＝″4-hydroxyproline(Pro)″Site 97/site_type＝″modified″/note＝″4-hydroxyproline(Pro)″Region 127..246/region_name＝″domain″/note＝″C-type lectin homology#label LCH″Bond bond(155，246)/bond_type＝″disulfide″Site 207/site_type＝″binding″/note＝″carbohydrate(Asn)(covalent)″Bond bond(224，238)/bond_type＝″disulfide″ORIGIN 1 mwlcplalnl ilmaasgavc evkdvcvgsp gipgtpgshg lpgrhgrdgl kgdlgppgpm61 gppgempcpp gndglpgapg ipgecgekge p9ergppglp ahldeelqat lhdfrhqilq121 trgalslqgs imtvgekvfs sngqsitfda iqeacaragg riavprnpee neaiasfvkk181 yntyayvglt egpspgdfry sdgtpvnytn wyrgepagrg keqcvemytd gqwndrncly241 srlticefSEQ ID NO98A53570 collectin-43-bovine gi|083017|pir||A53570[1083017]FEATURES Location/Qualifiers source 1..301/organism＝″Bos taurus″/db_xref＝″taxon:9913″Protein 1..301/product＝″collectin-43″/note＝″lectin CL-43″Region 177..299/region_name＝″domain″/note＝″C-type lectin homology#label LCH″ORIGIN 1 eemdvysekt ltdpctlvvc appadslrgh dgrdgkegpq gekgdpgppg mpgpagregp61 sgrqgsmgpp gtpgpkgepg peggvgapgm pgspgpaglk gergapgpgg aigpqgpsga121 mgppglkgdr gdpgekgarg etsvlevdtl rqrmrnlege vqrlqnivtq yrkavlfpdg181 qavgekifkt agavksysda eqlcreakgq lasprssaen eavtqlvrak nkhaylsmnd241 iskegkftyp tggsldysnw apgepnnrak degpenclei ysdgnwndie creerlvice 301 fSEQ ID NO99S33603 surfactant protein D-bovine gi|423283|pir||S33603[423283FEATURES Location/Qualifiers source 1..369/organism＝″Bos taurus″/db_xref＝″taxon:9913″Protein 1..369/product＝″surfactant protein D″Region 248..367/region_name＝″domain″/note＝″C-type lectin homology#label LCH″ORIGIN 1 mlllplsvll lltqpwrslg aemkiysqkt manactlvmc sppedglpgr dgrdgregpr61 gekgdpgspg pagragmpgp agpiglkgdn gsagepgpkg dtgppgppgm pgpagregps121 gkqgsmgppg tpgpkgdtgp kggvgapgiq gspgpaglkg ergapgdpga pgragapgpr181 gaigpqgpsg argppglkgd rgtpgergak gesglaevna lrqrvgileg qlqrlqnafs241 qykkamlfpn grsvgekifk tvgsektfqd aqqictqagg qlpsprsgae nealtqlata301 qnkaaflsms dtrkegtfiy ptgeplvysn wapqepnndg gsencveifp ngkwndkvcg 361eqrlvicefSEQ ID NO100AAF28384 lung surfactant protein A[Sus scrofa]gi|6782434|gb|AAF28384.1|AF133668_1[6782434]FEATURES Location/Qualifiers source 1..116/organism＝″Sus scrofa″/db_xref＝″taxon:9823″Protein＜1..116/product＝″lung surfactant protein A″/function＝″involved in the innate immunesystem and lipid homeostasis within the lung″/name＝″collectin；SPA；SP-A″CDS 1..116/gene＝″SFTPA″/coded_by＝″AF133668.1:＜1..353″ORIGIN 1 avgekvfstn gqsvafdvir elcaraggri aaprspeene aiasivkkhn tyaylglveg61 ptagdffyld gtpvnytnwy pgeprgrgke kcvemytdgq wndrncqqyr laicefSEQ ID NO101AAF22145 lung surfactant protein D precursor；SPD；SP-D；CP4[Sus scrofa]gi|6760482|gb|AAF22145.2|AF132496_1[6760482]sig_peptide 1..20mat_peptide 21..378/product＝″lung surfactant protein D″CDS 1..378/gene＝″SFTPD″/coded_by＝″AF132496.2:44..1180″ORIGIN 1 mlllplsvli lltqpprslg aemktysqravanacalvmc spmenglpgr dgrdgregpr61 gekgdpglpg avgragmpgl agpvgpkgdn gstgepgakg digpcgppgp pgipgpagke121 gpsgqqgnig ppgtpgpkge tgpkgevgal gmqgstgarg paglkgerga pgergapgsa
181 gaagpagatg pqgpsgargp pglkgdrgpp gergakgesg lpgitalrqq vetlqgqvqr241 lqkafsqykk velfpngrgv gekifktggf ektfqdaqqv ctqaggqmas prseteneal301 sqlvtaqnka aflsmtdikt egnftyptge plvyanwapg epnnnggssg aencveifpn 361gkwndkacge lrlvicefSEQ ID NO102P15783 PULMONARY SURFACTANT-ASSOCIATED PROTEIN C(SP-C)(PULMONARYSURFACTANT-ASSOCIATED PROTEOLIPID SPL(VAL))gi|131422|sp|P15783|PSPC_BOVIN[131422]FEATURES Location/Qualifers source 1..34/organism＝″Bos taaurus″/db_xref＝″taxon:9913″gene 1..34/gene＝″SFTPC″/note＝″SFTP2″Protein 1..34/gene＝″SFTPC″/product＝″PULMONARY SURFACTANT-ASSOCIATEDPROTEIN C″Site 4/gene＝″SFTPC″/site_type＝″lipid-binding″/note＝″PALMITATE(BY SIMILARITY).″Site 5/gene＝″SFTPC″/site_type＝″lipid-binding″/note＝″PALMITATE(BY SIMILARITY).″Region 21/gene＝″SFTPC″/region_name＝″Conflict″/note＝″L-＞V(IN REF.2).″Region 26/gene＝″SFTPC″/region_name＝″Conflict″/note＝″I-＞V(IN REF.2)″Region 28..34/gene＝″SFTPC″/region_name＝″Conflict″/note＝″GALLMGL-＞IGAMLAM(INREF.2).″ORIGIN 1 liccpvnik rllivvvvvv llvvvivgal lmglSEQ ID NO103P35246 PULMONARY SURFACTANT-ASSOCIATED PROTEIN D PRECURSOR(SP-D)(PSP-D)gi|464485|sp|P35246|PSPD_BOVIN[464485]FEATURES Location/Qualifiers source 1..369/organism＝″ Bos taurus″/db_xref＝″taxon:9913″gene 1..369/gene＝″SFTPD″/note＝″SFTP4″Protein 1..369/gene＝″SFTPD″/product＝″PULMONARY SURFACTANT-ASSOCIATEDPROTEIN D PRECURSOR″Region 1..20/gene＝″SFTPD″/region_name＝″Signal″/note＝″BY SIMILARITY.″Region 21..369/gene＝″SFTPD″/region_name＝″Mature chain″/note＝″PULMONARYSURFACTANT-ASSOCIATED PROTEIN D.″Region 46..216/gene＝″SFTPD″/region_name＝″Domain″/note＝″COLLAGEN-LIKE.″Site 78/gene＝″SFTPD″/site_type＝″hydtoxylation″/note＝″(BY SIMILARITY).″Site 87/gene＝″SFTPD″/site_type＝″hydroxylation″/note＝″(BY SIMILARITY).″Site 90/gene＝″SFTPD″/site_type＝″glycosylation″/note＝″POTENTIAL.″Site 96/gene＝″SFTPD″/site_type＝″hydroxylation″/note＝″(BY SIMILARITY).″Site 99/gene＝″SFTPD″/site_type＝″hydroxylation″/note＝″(BY SIMILARITY).″Site 165/gene＝″SFTPD″/site_type＝″hydroxylation″/note＝″(BY SIMILARITY).″Site 171/gene＝″SFTPD″/site_type＝″hydroxylation″/note＝″(BY SIMILARITY).″Region 217..248/gene＝″SFTPD″/region_name＝″Domain″/note＝″COILED COIL(POTENTIAL).″Region 273..369/gene＝″SFTPD″/region_name＝″Domain″/note＝″C-TYPE LECTIN(SHORTFORM).″Bond bond(275，367)/gene＝″SFTPD″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Bond bond(345，359)/gene＝″SFTPD″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″ORIGIN 1 mlllplsvll lltqpwrslg aemkiysqkt manactlvmc sppedglpgr dgrdgregpr61 gekgdpgspg pagragmpgp agpiglkgdn gsagepgpkg dtgppgppgm pgpagregps121 gkqgsmgppg tpgpkgdtgp kggvgapgiq gspgpaglkg ergapgepga pgragapgpa181 gaigpqgpsg argppglkgd rgtpgergak gesglaevna lrqrvgileg qlqrlqnafs241 qykkamlfpn grsvgekifk tvgsektfqd aqqictqagg qlpsprsgae nealtqlata301 qnkaaflsms dtrkegtfiy ptgeplvysn wapqepnndg gsencveifp ngkwndkvcg361 eqrlvicefSEQ ID NO104P42916 COLLECTIN-43(CL-43)gi|1168967|sp|P42916|CL43_BOVIN[1168967]FEATURES Location/Qualifiers source 1..301/organism＝″Bos taurus″/db_xref＝″taxon:9913″Protein 1..301/product＝″COLLECTIN-43″Region 29..142/region_name＝″Domain″/note＝″COLLAGEN-LIKE(G-X-Y).″Region 202..301/region_name＝″Domain″/note＝″C-TYPE LECTIN(SHORT FORM).″Bond bond(204，299)/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Bond bond(277，291)/bond_type＝″disulfide″/note＝″BY SIMILARITY.″ORIGIN 1 eemdvysekt ltdpctlvvc appadslrgh dgrdgkegpq gekgdpgppg mpgpagregp61 sgrqgsmgpp gtpgpkgepg peggvgapgm pgspgpaglk gergapgpgg aigpqgpsga121 mgppglkgdr gdpgekgarg etsvlevdtl rqrmrnlege vqrlqnivtq yrkavlfpdg181 qavgekifkt agavksysda eqlcreakgq lasprssaen eavtqlvrak nkhaylsmnd241 iskegkftyp tggsldysnw apgepgnrak degpenclei ysdgnwndie creerlvice301 fSEQ ID NO105CAB56155 DMBT1/8kb.2 protein[Homo sapiens]gi|5912464|emb|CAB56155.1|[5912464]sig_peptide 1..26mat_peptide 26..2412/product＝″DMBT1/8kb.2 protein″CDS 1..2412/gene＝″DMBT1″/coded_by＝″AJ243212.1:107..7345″/note＝″Sequence is analternative splice form of the DMBT1 gene that is expressed in human adult trachea.lsoformsof DMBT1 are identical to the collectin binding protein gp-340.Full-length cDNA clonecontains 1 bp deletions in codons 100 and 1751，that were corrected by compa rison with thegenomic exons″ORIGIN 1 mgistvilem cllwgqvlst ggwiprtdy aslipsevpl dttvaegspf pseltlestv61 aegspisles tlettvaegs lipsestles tvaegsdsgl alrlvngdgr cqgrveilyr121 gswgavcdds wdtndanvvc rqlgcgwams apgnawfgqg sgpialddvr csghesylws181 cphngwlshn cghgedagvi csaaqpqstl rpeswpvris ppvptegses slalrlvngg241 drcrgrvevl yrgswgtvcd dywdtndanv vcrqlgcgwa msapgnaqfg qgsgpivldd301 vrcsghesyl wscphngwlt hncghsedag vicsapqsrp tpspdtwpts hastagpess361 lalrlvnggd rcqgrvevly rgswgtvcdd swdtsdanvv crqlgcgwat sapgnarfgq421 gsgpivlddv rcsgyesylw scphngwlsh ncqhsedagv icsaahswst pspdtlptit481 lpastvgses slalrlvngg drcqgrvevl yrgswgtvcd dswdtndanv vcrqlgcgwa541 mlapgnarfg qgsgpivldd vrcsgnesyl wscphngwls hncghsedag vicsgpessl601 alrlvnggdr cqgrvevlyr gswgtvcdds wdtndanvvc rqlgcgwams apgnarfgqg661 sgpivlddvr csghesylws cpnngwlshn cghhedagvi csaaqsrstp rpdtlstitl721 ppstvgsess ltlrlvngsd rcqgrvevly rgswgtvcdd swdtndanvv crqlgcgwat781 sapgnarfgq gsgpivlddv rcsghesylw scphngwlsh ncghhedagv icsvsqsrpt841 pspdtwptsh astagpessl alrlvnggdr cqgrvevlyr gswgtvcdds wdtsdanvvc901 rqlgcgwats apgnarfgqg sgpivlddvr csgyesylws cphngwlshn cqhsedagvi961 csaahswstp spdtlptitl pastvgsess lalrlvnggd rcqgrvevly qgswgtvcdd1021 swdtndanvv crqlgcgwam sapgnarfgq gsgpivldda rcsghesylw scphngwlsh1081 ncghsedagv icsasqsrpt pspdtwptsh astagsessl alrlvnggdr cqgrvevlyr1141 gswgtvcddy wdtndanvac rqlgcgwams apgnarfgqg sgpivlddvr csghesylws1201 cphngwlshn cghhedagvi csasqsqptp spdtwptsha stagsessla lrlvnggdrc1261 qgrvevlyrg swgtvcddyw dtndanvvcr qlgcgwatsa pgnarfgqgs gpivlddvrc1321 sghesylwsc phngwlshnc ghhedagvic sasqsqptps pdtwptshas tagsesslal1381 rlvnggdrcq grvevlyrgs wgtvcddywd tndanvvcrq lgcgwatsap gnarfgqgsg1441 pivlddvrcs ghesylwscp hngwlshncg hhedagvics afqsqptpsp dtwptsrast1501 agsestlalr lvnggdrcrg rvevlyqgsw gtvcddywdt ndanvvcrql gcgwamsapg1561 naqfgqgsgp ivlddvrcsg hepylwscph ngwlshncgh hedagvicsa aqsqstprpd1621 twlttnlpal tvgsesslal rlvnggdrcr grvevlyrgs wgtvcddswd tndanvvcrq1681 lgcgwamsap gnarfgqgsg pivlgdvrcs gnesylwscp hkgwlthncg hhedagvics1741 atqinstttd wwhpttttta rpssncggfl fyasgtfssp sypayypnna kcvweievns1801 gyrinlgfsn lkleahhncs fdyveifdgs lnsslllgki cndtrqifts synrmtihfr1861 sdisfqntgf lawynsfpsd atlrlvnlns syglcagrve iyhggtwgav cddswtiqea1921 evvcrqlgcg ravsalgnay fgsgsgpitl ddvecsgtes tlwqcrnrgw fshncnhred1981 agvicsgnhl stpapflnit rpnnyscggf lsqpsgdfss pfypgnypnn akcvwdievq2041 nnyrvtvifr dvqleggcny dyievfdgpy rsspliarvc dgargsftss snfmsirfis2101 dhsitrrgfr aeyysspsnd stnllclpnh mqasvsrsyl qslgfsasdl vistwngyye2161 crpqitpnlv iftipysgcg tfkqadndti dysnlltaav sggiikrrtd lrihvscrml2221 qntwvdtmyi andtihvann tiqveevqyg nfdvnisfyt sssflypvts rpyyvdlnqd2281 lyvqaeilhs davltlfvdt cvaspysndf tsltydlirs gcvrddtygp ysspslriar2341 frfrafhfln rfpsvylrck mvvcraydps srcyrgcvlr skrdvgsyqe kvdvvlgpiq2401 lqtpprreee prSEQ ID NO106AAD49696 gp-340 variant protein[Homo sapiens]gi|5733598|gb|AAD49696.1|AF159456_1[5733598]FEATURES Location/Qualifiers source 1..2413/organism＝″Homosapiens″/db_xref＝″taxon:9606″/chromosome＝″10″/map＝″10q25.3-26.1″Protein 1..2413/product＝″gp-340 variant protein″/name＝″scavenger receptor cysteine-richprotein SRCR″/note＝″putative receptor for SP-D″CDS 1..2413/gene＝″DMBT1″/coded_by＝″AF159456.1:107..7348″ORIGIN 1 mgistvilem cllwgqvlst ggwiprttdy aslipsevpl dqtvaegspf psestlesta61 aegspisles tlestvaegs lipsestles tvaegsdsgl alrlvngdgr cqgrveilyr121 gswgtvcdds wdtndanvvc rqlgcgwams apgnawtgqg sgpialddvr csghesylws181 cphngwlshn cghgedagvi csaaqpqstl rpeswpvris ppvptegses slalrlvngg241 drcrgrvevl yrgswgtvcd dywdtndanv vcrqlgcgwa msapgnaqfg qgsgpivldd301 vrcsghesyl wscphngwlt hncghsedag vicsapqsrp tpspdtwpts hastagpess361 lalrlvnggd rcqgrvevly rgswgtvcdd swdtsdanvv crqlgcgwat sapgnarfgq421 gsgpivlddv rcsgyesylw scphngwlsh ncqhsedagv icsaahswst pspdtlptit481 lpastvgses slalrlvngg drcqgrvevl yrgswgtvcd dswdtndanv vcrqlgcgwa541 mlapgnarfg qgsgpivldd vrcsgnesyl wscphngwls hncghsedag vicsgpessl601 alrlvnggdr cqgrvevlyr gswgtvcdds wdtndanvvc rqlgcgwams apgnarfgqg661 sgpivlddvr csghesylws cpnngwlshn cghhedagvi csaaqsrstp rpdtlstitl721 ppstvgsess ltlrlvngsd rcqgrvevly rgswgtvcdd swdtndanvv crqlgcgwam781 sapgnarfgq gsgpivlddv rcsghesylw scphngwlsh ncghhedagv icsvsqsrpt841 pspdtwptsh astagsessl alrlvnggdr cqgrvevlyr gswgtvcdds wdtsdanvvc901 rqlgcgwats apgnarfgqg sgpivlddvr csgyesylws cphngwlshn cqhsedagvi961 csaahswstp spdtlptitl pastvgsess lalrlvnggd rcqgrvevly qgswgtvcdd1021 swdtndanvv crqpgcgwam sapgnarfgq gsgpivlddv rcsghesypw scphngwlsh1081 ncghsedagv icsasqsrpt pspdtwptsh astagsessl alrlvnggdr cqgrvevlyr1141 gswgtvcddy wdtndanvvc rqlgcgwams apgnarfgqg sgpivlddvr csghesylws1201 cphngwlshn cghhedagvi csasqsqptp spdtwptsha stagsessla lrlvnggdrc1261 qgrvevlyrg swgtvcddyw dtndanvvcr qlgcgwatsa pgnarfgqgs gpivlddvrc1321 sghesylwsc phngwlshnc ghhedagvic sasqsqptps pdtwptshas tagsesslal1381 rlvnggdrcq grvevlyrgs wgtvcddywd tndanvvcrq lgcgwatsap gnarfgqgsg1441 pivlddvrcs ghesylwscp hngwlshncg hhedagvics asqsqptpsp dtwptsrast1501 agsestlalr lvnggdrcrg rvevlyqgsw gtvcddywdt ndanvvcrql gcgwamsapg1561 naqfgqgsgp ivlddvrcsg hesylwscph ngwlshncgh hedagvicsa aqsqstprpd1621 twlttnlpal tvgsesslal rlvnggdrcr grvevlyrgs wgtvcddswd tndanvvcrq1681 lgcgwamsap gnarfgqgsg pivlddvrcs gnesylwscp hkgwlthncg hhedagvics1741 atqinstttd wwhpttttta rpssncggfl fyasgtfssp sypayypnna kcvweievns1801 gyrinlgfsn lkleahhncs fdyveifdgs lnsslllgki cndtrqifts synrmtihfr1861 sdisfqntgf lawynsfpsd atlrlvnlns syglcagrve iyhggtwgtv cddswtiqea1921 evvcrqlgcg ravsalgnay fgsgsgpitl ddvecsgtes tlwqcrnrgw fshncnhred1981 agvicsgnhl stpapflnit rpntdyscgg flsqpsgdfs spfypgnypn nakcvwdiev2041 qnnyrvtvif rdvqleggcn ydyievfdgp yrsspliarv cdgargsfts ssnfmsirfi2101 sdhsitrrgf raeyysspsn dstnllclpn hmqasvsrsy lqslgfsasd lvistwngyy2161 ecrpqitpnl viftipysgc gtfkqadndt idysnfltaa vsggiikrrt dlrihvscrm2221 lqntwvdtmy iandtihvan ntiqveevqy gnfdvnisfy tsssflypvt srpyyvdlnq2281 dlyvqaeilh sdavltlfvd tcvaspysnd ftsltydlir sgcvrddtyg pysspslria2341 rfrfrafhfl nrfpsvylrc kmvvcraydp ssrcyrgcvl rskrdvgsyq ekvdvvlgpi2401 qlqtpprree eprSEQ ID NO107AAD31380 surfactant protein D precursor[Mus musculus]gi|4877556|gb|AAD31380.1|AF047742_1[4877556]sig_peptide 1..19mat_peptide 20..374/product＝″surfactant protein D″CDS 1..374/gene＝″Sftp4″/coded_by＝″join(AF047741.1:5705..5900，AF047742.1:312.428，AF047742.1:669..785，AF047742.1:1112..1228，AF047742.1:1977..2093，AF047742.1:3162..3245，AF047742.1:5010..5386)″ORIGIN 1 mlpflsmlvl lvqplgnlga emkslsqrsv pntctlvmcs ptenglpgrd grdgregprg61 ekgdpglpgp mglsglqgpt gpvgpkgeng sagepgpkge rglsgppglp gipgpagkeg121 psgkqgnigp qgkpgpkgea gpkgevgapg mqgstgAkgs tgpkgergap gvqgapgnag181 aagpagpagp qgapgsrgpp glkgdrgvpg drgikgesgl pdsaalrqqm ealkgklqrl241 evafshyqka alfpdgrsvg dkifrtadse kpfedaqemc kqaggqlasp rsatenaaiq301 qlitahnkaa flsmtdvgte gkftyptgep lvysnwapge pnnnggaenc veiftngqwn361 dkacgeqrlv icefSEQ ID NO108B61249 pulmonary surfactant protein C-dog gi|539712|pir||B61249[539712]FEATURES Location/Qualifiers source 1..35/organism＝″Canisfamiliaris″/db_xref＝″taxon:9615″Protein 1..35/product＝″pulmonary surfactant protein C″ORIGIN 1 lgipcfpssl krlliivvvi vlvvvvivga llmglSEQ ID NO109S00609 pulmonary surfactant protein C-bovine gi|89749|pir||S00609[89749]FEATURES Location/Qualifiers source 1..34/organism＝″Bos taurus″/db_xref＝″taxon:9913″Protein 1..34/product＝″pulmonary surfactant protein C″/note＝″pulmonary surfactant proteinPSP-6″Site 4/site_type＝″binding″/note＝″palmitate(Cys)(covalent)″Site 5/site_type＝″binding″/note＝″palmitate(Cys)(covalent)″ORIGIN 1 lipccpvnik rllivvvvvv llvvvivgal lmglSEQ ID NO110A43628 pulmonary surfactant protein A-human(fragments)gi|280854|pir||A43628[280854]FEATURES Location/Qualifiers source 1..35/organism＝″Homosapiens″/db_xref＝″taxon:9606″Protein 1..35/product＝″pulmonary surfactant protein A″ORIGIN 1 gqsitfdagk eqcvemytdg qwndrnclyl ticefSEQ ID NO111AAB48076 Surfactant protein B(SP-B)[Oryctolagus cuniculus]gi|1850933|gb|AAB48076.1|[1850933]FEATURES Location/Qualifiers source 1..370/organism＝″Oryctolaguscuniculus″/db_xref＝″taxon:9986″/tissue_type＝″liver″Protein 1..370/product＝″Surfactant protein B(SP-B)″CDS 1..370/gene＝″SP-B″/coded_by＝″join(U40853.1:2194..2263，U40853.1:2591..2718，U40853.1:2941..3012，U40853.1:3257..3382，U40853.1:3590..3727，U40853.1:3925..4014，U40853.1:6043..6226，U40853.1:6421..6581，U40853.1:7266..7346，U40853.1:7829..7891)″/note＝″Surfactant protein B(SP-B)is a keycomponent of lung surfactant，a surface a ctive material secreted by type ll epithelial cells oflung alveolus；SP-B maintains biophysical properties and physiological function of surfactant；Pulmonary surfactant associated protein″ORIGIN 1 makshlppwl lllllptlcg pgtavwatsp lacaqgpefw cqsleqalqc kalghclqev61 wghvgaddlc qecqdivnil tkmtkeaifq dtirkflehe cdvlplkllv pqchhvldvy121 fpltityfls qinakaicqh lglcqpgspe ppldplpdkl vlptllgalp akpgphtqdl181 saqrfpiplp lcwlcrtllk riqamipkgv lamavaqvch vvplvvggic qclaerytvi241 llevllghvl pqlvcglvlr cssvdsigqv pptlealpge wlpqdpecpl cmsvttqarn301 iseqtrpqav yhaclssqld kqeceqfvel htpqllslls rgwdaraicq algacvatls361 plqciqsphfSEQ ID NO1121901176A surfactant protein A gi|382753|prf||1901176A[382753]FEATURES Location/Qualifiers source 1..247/organism＝″Oryctolaguscuniculus″/db_xref＝″taxon:9986″ORIGIN 1 mlllslaltl isapasdtcd tkdvcigspg ipgtpgshgl pgrdgrdgvk gdpgppgpmg61 ppggmpglpg rdgligapgv pgergdkgep gergppglpa yldeelqatl helrhhalqs121 igvlslqgsm kavgekifst ngqsvnfdai revcaraggr iaivkevprs leeneaiasr181 ntyaylglae gptagdfyyl dgdpvnytnw ypgeprgqgr ekcvemytdg kwndknclqy241 rlvicefSEQ ID NO113CAA53510 lung surfactant protein D[Bos taurus]gi|415939|emb|CAA53510.|1[415939]sig_peptide 1..20mat_peptide 21..369/product＝″lung surfactant protein D″CDS 1..369/coded_by＝″X75911.1:102..1211″/db_xref＝″SWISS-PROT:P35246″ORIGIN 1 mlllplsvll lltqpwrslg aemkiysqkt manactlvmc sppedglpgr dgrdgregpr61 gekgdpgspg pagragmpgp agpiglkgdn gsagepgpkg dtgppgppgm pgpagregps121 gkqgsmgppg tpgpkgdtgp kggvgapgiq gspgpaglkg ergapgepga pgragapgpa181 gaigpqgpsg argppglkgd rgtpgergak gesglaevna lrqnvgileg qlqrlqnafs241 qykkamlfpn grsvgekifk tvgsektfqd aqqictqagg qlpsprsgae nealtqlata301 qnkaaflsms dtrkegtfiy ptgeplvysn wapqepnndg gsencveifp ngkwndkvcg361 eqrlvicefSEQ ID NO114CAA53511 collectin-43[Bos taurus]gi|499385|emb|CAA53511.1|[499385]FEATURES Location/Qualifiers source 1..301/organism＝″Bostaurus″/db_xref＝″taxon:9913″/tissue_type＝″liver″/clone_lib＝″lambda gt 11″Protein 1..301/product＝″collectin-43″mat_peptide 1..301/product＝″collectin-43″CDS 1..301/coded_by＝″X75912.1:＜1..906″/db_xref＝″SWISS-PROT:P42916″ORIGIN 1 eemdvyxekt ltdpctlvvc appadslrgh dgrdgkegpq gekgdpgppg mpgpagregp61 sgrqgsmgpp gtpgpkgepg peggvgapgm pgspgpaglk gergapgpgg aigpqgpsga121 mgppglkgdr gdpgekgarg etsvlevdtl rqrmrnlege vqrlqnivtq yrkavlfpdg181 qavgekifkt agavksysda eqlcreakgq lasprssaen eavtqlvrak nkhaylsmnd241 iskegkftyp tggsldysnw apgepgnrak degpenclei ysdgnwndie creerlvice301 fSEQ ID NO115CAA46152 lung surfactant protein D[Homo sapiens]gi|34767|emb|CAA46152.1|[34767]sig_peptide 1..20mat_peptide 21..375/product＝″lung surfactant protein D″CDS1..375/gene＝″hsp-D″/coded_by＝″X65018.1:172..1299″/db_xref＝″SWISS-PROT:P35247″ORIGIN 1 mllfllsalv lltqplgyle aemktyshrt tpsactlvmc ssvesglpgr dgrdgregpr61 gekgdpglpg aagqagmpgq agpvgpkgdn gsvgepgpkg dtgpsgppgp pgvpgpagre121 gplgkqgnig pqgkpgpkge agpkgevgap gmqgsagarg lagpkgergv pgergvpgna181 gaagsagamg pqgspgargp pglkgdkgip gdkgakgesg lpdvaslrqq vealqgqvqh241 lqaafsqykk velfpngqsv gekifktagf vkpfteaqll ctqaggqlas prsaaenaal301 qqlvvaknea aflsmtdskt egkftyptge slvysnwapg epnddggsed cveiftngkw361 ndracgekrl vvcefSEQ ID NO116AAA92788 lung surfactant protein C[Rattus norvegicus]gi|595282|gb|AAA92788.1|[595282]FEATURES Location/Qualifiers source 1..194/organism＝″Rattusnorvegicus″/db_xref＝″taxon:10116″/clone＝″sp-c″/tissue_type＝″liver″Protein 1..194/product＝″lung surfactant protein C″CDS 1..194/gene＝″sp-c″/coded_by＝″join(U07796.1:1673..1714，U07796.1:2841..2999，U07796.1:3252..3377，U07796.1:3598..3707，U07796.1:4053..4200)″ORIGIN 1 mdmgskevlm esppdystgp rsqfripccp vhlkllivv vvvvlvvvvi vgallmglhm61 sqkhtemvle msiggapetq krlalsehtd tiatfsigst givlydyqrl ltaykpapgt121 ycyimkmape sipslealar kfknfqakss tptsklgqee ghsagsdsds sgrdlaflgl181 avstlcgvlp lyyiSEQ ID NO117AAA31468 surfactant protein A[Oryctolagus cuniculus]gi|431446|gb|AAA31468.1|[431446]FEATURES Location/Qualifiers source 1..247/organism＝″Oryctolaguscuniculus″/strain＝″New ZealandWhite″/db_xref＝″taxon:9986″/tissue_type＝″liver″/dev_stage＝″adult″Protein 1..247/product＝″surfactant protein A″CDS 1..247/coded_by＝″join(L19387.1:3864..4032，L19387.1:4241..4360.L19387.1:5010..5087，L19387.1:5533..5909)″ORIGIN 1 mlllslaltl isapasdtcd tkdvcigspg ipgtpgshgl pgrdgrdgvk gdpgppapwa61 ppggmpglpg rdgligapgv pgergdkgep gergppglpa yldeelqatl helrhhalqs121 igvlslqgsm kavgekifst ngqsvnfdai revcaraggr iavprsleen eaiasivker181 ntyaylglae gptagdfyyl dgdpvnytnw ypgeprgqgr ekcvemytdg kwndknclqy241 rlvicef結(jié)合甘露糖的凝集素SEQ ID NO1NP_034897 mannan-binding lectin serine protease 2[Mus musculus]gi|6754642|ref|NP_034897.1|[6754642]sig_peptide 1..15mat_peptide 16..185/product＝″mannan-binding lectin serine protease 2″Region 28..137/region_name＝″Domain first found in C1r，C1s，uEGF，and bonemorphogenetic protein″/note＝″CUB″/db_xref＝″CDD:smart00042″Region 28..134/region_name＝″CUB domain″/note＝″CUB″/db_xref＝″CDD:pfam00431″Region 138..180/region_name＝″Calcium-binding EGF-likedomain″/note＝″EGF_CA″/db_xref＝″CDD:smart00179″variation 172/allele＝″I″/allele＝″V″/db_xref＝″dbSNP:3167338″CDS1..185/gene＝″Masp2″/coded_by＝″NM_010767.1:32..589″/db_xref＝″LocusID:17175″/db_xref＝″MGD:1330832″ORIGIN 1 mrlliflgll wslvatllgs kwpepvfgrl vspgfpekya dhqdrswtlt appgyrlrly61 fthfdlelsy rceydfvkls sgtkvlatlc gqestdteqa pgndtfyslg pslkvtfhsd121 ysnekpftgf eafyaaedvd ecrvslgdsv pcdhychnyl ggyycscrag yvlhqnkhtc181 seqslSEQ ID NO2AAH10760 Similar to mannose binding lectin，serum(C)[Mus musculus]gi|14789670|gb|AAH10760.1|[14789670]source 1..244/organism＝″Musmusculus″/strain＝″FVB/N″/db_xref＝″taxon:10090″/clone＝″MGC:18500IMAGE:4212216″/tissue_type＝″Liver，normal.5 month old malemouse.″/clone_lib＝″NCI_CGAP_Li9″/lab_host＝″DH10B″/note＝″Vector:pCMV-SPORT6″Protein 1..244/product＝″Similar to mannose binding lectin，serum(C)″CDS 1..244/coded_by＝″BC010760.1:192..926″ORIGIN 1 msiftslll cvvtvvyaet ltegvqnscp vvtcsspgln gfpgkdgrdg akgekgepgq61 glrglqgppg kvgptgppgn pglkgavgpk gdrgdraefd tseidseiaa lrselralrn121 wvlfslsekv gkkyfvssvk kmsldrvkal csefqgsvat prnaeensai qkvakdiayl181 gitdvrvegs fedltgnrvr ytnwndgepn ntgdgedcvv ilgngkwndv pcsdsflaic241 efsdSEQ ID NO3AAH21762 mannose binding lectin，liver(A)[Mus musculus]gi|8256010|gb|AAH21762.1][18256010]source 1..239/organism＝″Musmusculus″/strain＝″FVB/N″/db_xref＝″taxon:10090″/clone＝″MGC:30242IMAGE:5132514″/tissue_type＝″Liver，normal.5 month old malemouse.″/clone_lib＝″NCI_CGAF_Li9″/lab_host＝″DH10B″/note＝″Vector:pCMV-SPORT6″Protein 1..239/product＝″mannose binding lectin，liver(A)″/db_xref＝″LocusID:17194″CDS 1..239/coded_by＝″BC021762.1:75..794″/db_xref＝″LocusID:17194″ORIGIN 1 mlllpllpvl lcvvsvsssg sqtcedtlkt csviacgrdg rdgpkgekge pgqglrglqg61 ppgklgppgs vgspgspgpk gqkgdhgdnr aieeklanme aeirilkskl qltnklhafs121 mgkksgkklf vtnhekmpfs kvkslctelq gtvaiprnae enkaiqevat giaflgitde181 ategqfmyvt ggrltysnwk kdepnnhgsg edcviildng lwndiscqas fkavcefpaSEQ ID NO4Q9NPY3 Complement component C1q receptor precursor(Complement component 1，qsubcomponent，receptor 1)(C1qRp)(C1qR(p))(C1q/MBL/SPA receptor)(CD93 antigen)(CDw93)gi|21759074|sp|Q9NPY3|CD93_HUMAN[21759074]source 1..652/organism＝″Homo sapiens″/db_xref＝″taxon:9606gene 1..652/gene＝″C1QR1″/note＝″CD93″Protein 1..652/gene＝″C1QR1″/pnoduct＝″Complement component C1q receptor p recursor″Region 1..21/gene＝″C1QR1″/region_name＝″Signal″Region 22..652/gene＝″C1QR1″/region_name＝″Mature chain″/note＝″COMPLEMENTCOMPONENT C1Q RECEPTOR.Region 22/gene＝″C1QR1″/region_name＝″Conflict″/note＝″T-＞V(IN AA SEQUENCE).″Region 24..580/gene＝″C1QR1″/region_name＝″Domain″/note＝″EXTRACELLULAR(POTENTIAL).”Region 32..174/gene＝″C1QR1″/region_name＝″Domain″/note＝″C-TYPE LECTIN.″Region 36/gene＝″C1QR1″/region_name＝″Conflict″/note＝″C-＞T(IN AA SEQUENCE).″Region 38..39/gene＝″C1QR1″/region_name＝″Conflict″/note＝″TA-＞RI(IN AASEQUENCE).″Region 155/gene＝″C1QR1″/region_name＝″Conflict″/note＝″S-＞N(IN REF.1).″Region 186/gene＝″C1QR1″/region_name＝″Conflict″/note＝″G-＞A(IN AA SEQUENCE).″Region 260..301/gene＝″C1QR1″/region_name＝″Domain″/note＝″EGF-LIKE 1.″Bond bond(264，275)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Bond bond(271，285)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Bond bond(287，300)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Region 302..344/gene＝″C1QR1″/region_name＝″Domain″/note＝″EGF-LIKE 2.″Bond bond(306，317)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Bond bond(311，328)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Region 318/gene＝″C1QR1″/region_name＝″Variant″/note＝″V-＞A./FTId＝VAR_013573.″Site 325/gene＝″C1QR1″/site_type＝″glycosylation″/note＝″N-LINKED(GLCNAC...)(POTENTIAL).″Bond bond(330，343)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Region 345..384/gene＝″C1QR1″/region_name＝″Domain″/note＝″EGF-LIKE 3，CALCIUM-BINDING(POTENTIAL).″Bond bond(349，358)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Bond bond(354，367)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Bond bond(369，383)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Region 385..426/gene＝″C1QR1″/region_name＝″Domain″/note＝″EGF-LIKE 4，CALCIUM-BINDING(POTENTIAL).″Bond bond(389，400)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Bond bond(396，409)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Bond bond(411，425)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Region 427..468/gene＝″C1QR1″/region_name＝″Domain″/note＝″EGF-LIKE 5，CALCIUM-BINDING(POTENTIAL).″Bondbond(431，443)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Bond bond(439，452)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Bond bond(454，467)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Region 492/gene＝″C1QR1″/region_name＝″Conflict″/note＝″S-＞A(IN AA SEQUENCE).″Region 496/gene＝″C1QR1″/region_name＝″Conflict″/note＝″R-＞Q(IN AA SEQUENCE).″Region 504/gene＝″C1QR1″/region_name＝″Conflict″/note＝″R-＞G(IN AA SEQUENCE).″Region 541/gene＝″C1QR1″/region_name＝″Conflict″/note＝″P-＞S(IN REF.1).″Region 581..601/gene＝″C1QR1″/region_name＝″Transmembraneregion″/note＝″POTENTIAL.″Region 594..601/gene＝″C1QR1″/region_name＝″Domain″/note＝″POLY-LEU.″Region 602..652/gene＝″C1QR1″/region_name＝″Domain″/note＝″CYTOPLASMIC(POTENTIAL).″ORIGIN 1 matsmgllll llllltqpga gtgadteavv cvgtacytah sgklsaaeaq nhcnqnggnl61 atvkskeeaq hvqrvlaqll rreaaltarm skfwiglqre kgkcldpslp lkgfswvggg121 edtpysnwhk elrnsciskr cvsllldlsq pllpsrlpkw segpcgspgs pgsniegfvc181 kfsfkgmcrp lalggpgqvt yttpfqttss sleavpfasa anvacgegdk detqshyflc241 kekapdvfdw gssgplcvsp kygcnfnngg chqdcfeggd gsflcgcrpg frllddlvtc301 asrnpcsssp crggatcvlg phgknytcrc pqgyqldssq ldcvdvdecq dspcaqecvn361 tpggfrcecw vgyepggpge gacqdvdeca lgrspcaqgc tntdgsfhcs ceegyvlage421 dgtqcqdvde cvgpggplcd slcfntqgsf hcgclpgwvl apngvsctmg pvslgppsgp481 pdeedkgeke gstvpraata sptrgpegtp katpttsrps lssdapitsa plkmlapsgs541 pgvwrepsih hataasgpqe paggdssvat qnndgtdgqk lllfyilgtv vaillllala601 lgllvyrkrr akreekkekk pqnaadsysw vperaesram enqysptpgt dcSEQ ID NO5O89103 Complement component C1q receptor precursor(Complement component 1，qsubcomponent，receptor 1)(C1qRp)(C1qR(p))(C1q/MBL/SPA receptor)(CD93 antigen)(Cellsurface antigen AA4)(Lymphocyte antigen 68)gi|21541998|sp|O89103|CD93_MOUSE[21541998source 1..644/organisn＝″Mus musculus″/db_xref＝″taxon:10090″gene 1..644/gene＝″C1QR1″/note＝″CD93；C1QRP；LY68；AA4″Protein 1..644/gene＝″C1QR1″/product＝″Complement component C1q receptor precursor″Region 1..22/gene＝″C1QR1″/region_name＝″Signal″/note＝″POTENTIAL″Region 23..644/gene＝″C1QR1″/region_name＝″Mature chain″/note＝″COMPLEMENTCOMPONENT C1Q RECEPTOR.″Region 23..572/gene＝″C1QR1″/region_name＝″Domain″/note＝″EXTRACELLULAR(POTENTIAL).″Region 31..173/gene＝″C1QR1″/region_name＝″Domain″/note＝″C-TYPE LECTIN.″Site 102/gene＝″C1QR1″/site_type＝″glycosylation″/note＝″N-LINKED(GLCNAC...)(POTENTIAL).″Region 257..298/gene＝″C1QR1″/region_name＝″Domain″/note＝″EGF-LIKE 1.″Bond bond(261，272)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Bond bond(268，282)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Bond bond(284，297)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Region 299..341/gene＝″C1QR1″/region_name＝″Domain″/note＝″EGF-LIKE 2.″Bond bond(303，314)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Bond bond(308，325)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Site 322/gene＝″C1QR1″/site_type＝″glycosylation″/note＝″N-LINKED(GLCNAC...)(POTENTIAL).″Bond bond(327，340)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Region 342..381/gene＝″C1QR1″/region_name＝″Domain″/note＝″EGF-LIKE 3，CALCIUM-BINDING(POTENTIAL).″Bond bond(346，355)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Bond bond(351，364)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Bond bond(366，380)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Region 382..423/gene＝″C1QR1″/region name＝″Domain″/note＝″EGF-LIKE 4，CALCIUM-BINDING(POTENTIAL).″Bond bond(386，397)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Bond bond(393，406)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Bond bond(408，422)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Region 424..465/gene＝″C1QR1″/region_name＝″Domain″/note＝″EGF-LIKE 5，CALCIUM-BINDING(POTENTIAL).″Bond bond(428，440)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Bond bond(436，449)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY″Bond bond(451，464)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Region 573..593/gene＝″C1QR1″/region_name＝″Transmembraneregion″/note＝″POTENTIAL.″Region 594..644/gene＝″C1QR1″/region_name＝″Domain″/note＝″CYTOPLASMIC(POTENTIAL).″ORIGIN 1 maistglfll lgllgqpwag aaadsqavvc egtacytahw gklsaaeaqh rcnenggnla61 tvkseeearh vqqaltqllk tkapleakmg kfwiglqrek gnctyhdlpm rgfswvggge121 dtaysnwyka sksscifkrc vslildlslt phpshlpkwh espcgtpeap gnsiegflck181 fnfkgmcrpl alggpgrvty ttpfqattss leavpfasva nvacgdeaks ethyflcnek241 tpgifhwgss gplcvspkfg csfnnggcqq dcfeggdgsf rcgcrpgfrl lddlvtcasr301 npcssnpctg ggmchsvpls enytcrcpsg yqldssqvhc vdidecqdsp caqdcvntlg361 sfhcecwvgy qpsgpkeeac edvdecaaan spcaqgcint dgsfycscke gyivsgedst421 qcedidecsd angnpcdslc fntdgsfrcg cppgwelapn gvfcsrgtvf selparppqk481 ednddrkest mpptempssp sgskdvsnra qttglfvqsd iptasvplei eipsevsdvw541 felgtylptt sghskpthed svsahsdtdg qnlllfyilg tvvaislllv lalgiliyhk601 rrakkeeike kkpq naadsy swvperaesq apenqysptp gtdcSEQ ID NO6P09871 Complement C1s component precursor(C1 esterase)gi|115205|sp|P09871|C1S_HUMAN[115205]source 1..688/organism＝″Homo sapiens″/db_xref＝″taxon:9606″gene 1..688/gene＝″C1S″Protein 1..688/gene＝″C1S″/product＝″Complement C1s componentprecursor″/EC_number＝″3.4.21.42″Region 1..15/gene＝″C1S″/region_name＝″Signal″Region 16..437/gene＝″C1S″/region_name＝″Mature chain″/note＝″COMPLEMENT C1SHEAVY CHAIN.″Region 16..130/gene＝″C1S″/region_name＝″Domain″/note＝″CUB 1.″Bond bond(65，83)/gene＝″C1S″/bond_type＝″disulfide″Region 131..172/gene＝″C1S″/region_name＝″Domain″/note＝″EGF-LIKE，CALCIUM-BINDING(POTENTIAL).″Bond bond(135，147)/gene＝″C1S″/bond_type＝″disulfide″Bond bond(143，156)/gene＝″C1S″/bond_type＝″disulfide″Site 149/gene＝″C1S″/site_type＝″hydroxylation″/note＝″(PROBABLE).″Bond bond(158，171)/gene＝″C1S″/bond_type＝″disulfide″Site 174/gene＝″C1S″/site_type＝″glycosylation″/note＝″N-LINKED(GLCNAC...).″Region 175..290/gene＝″C1S″/region_name＝″Domain″/note＝″CUB 2.″Bond bond(175，202)/gene＝″C1S″/bond_type＝″disulfide″Bondbond(234，251)/gene＝″C1S″/bond_type＝″disulfide″Region293..355/gene＝″C1S″/region_name＝″Domain″/note＝″SUSHI 1.″Bond bond(294，341)/gene＝″C1S″/bond_type＝″disulfide″Region 294/gene＝″C1S″/region_name＝″Conflict″/note＝″C-＞K(IN REF.6).″Bond bond(321，354)/gene＝″C1S″/bond_type＝″disulfide″Region 358..422/gene＝″C1S″/region_name＝″Domain″/note＝″SUSHI 2.″Bond bond(359，403)/gene＝″C1S″/bond_type＝″disulfide″Bond bond(386，421)/gene＝″C1S″/bond_type＝″disulfide″Site 406/gene＝″C1S″/site_type＝″glycosylation″/note＝″N-LINKED(GLCNAC...).″Bond bond(425，549)/gene＝″C1S″/bond_type＝″disulfide″/note＝″INTERCHAIN.″Region 438..688/gene＝″C1S″/region_name＝″Mature chain″/note＝″COMPLEMENT C1SLIGHT CHAIN.″Region 438..688/gene＝″C1S″/region_name＝″Domain″/note＝″SERINEPROTEASE″Site 475/gene＝″C1S″/site_type＝″active″/note＝″CHARGE RELAY SYSTEM.″Region 513/gene＝″C1S″/region_name＝″Conflict″/note＝″G-＞GG(IN REF.5).″Site 529/gene＝″C1S″/site_type＝″active″/note＝″CHARGE RELAY SYSTEM.″Region 573/gene＝″C1S″/region_name＝″Conflict″/note＝″T-＞A(IN REF.7).″Bond bond(595，618)/gene＝″C1S″/bond_type＝″disulfide″Bond bond(628，659)/gene＝″C1S″/bond_type＝″disulfide″Site 632/gene＝″C1S″/site_type＝″active″/note＝″CHARGE RELAY SYSTEM.″Region 645..646/gene＝″C1S″/region_name＝″Conflict″/note＝″TK-＞GR(IN REF.7).″ORIGIN 1 mwcivlfsllawvyaeptmy geilspnypq aypseveksw dievpegygi hlyfthldie61 lsencaydsv qiisgdteeg rlcgqrssnn phspiveefq vpynklqvif ksdfsneerf121 tgfaayyvat dinectdfvd vpcshfcnnf iggyfcscpp eyflhddmkn cgvncsgdvf181 taligeiasp nypkpypens rceyqirlek gfqvvvtlrr edfdveaads agncldslvf241 vagdrqfgpy cghgfpgpln ietksnaldi ifqtdltgqk kgwklrvhgd pmpcpkedtp301 nsvwepakak yvfrdvvqit cldgfevveg rvgatsfyst cqsngkwsns klkcqpvdcg361 ipesiengkv edpestlfgs virytceepy yymengggge yhcagngswv nevlgpelpk421 cvpvcgvpre pfeekqriig gsdadiknfp wqvffdnpwa ggalineywv ltaahvvegn481 reptmyvgst svqtsrlaks kmltpehvfi hpgwkllevp egrtnfdndi alvrlkdpvk541 mgptvspicl pgtssdynlm dgdlglisgw grtekrdrav rlkaarlpva plrkckevkv601 ekptadaeay vftpnmicag gekgmdsckg dsggafavqd pndktkfyaa glvswgpqcg661 tyglytrvkn yvdwimktmq enstpredSEQ ID NO7NP_036204 complement component 1，q subcomponent，receptor 1；complement componentC1q receptor[Homo sapiens]gi|6912282|ref|NP_036204.1|[6912282]source 1..652/organism＝″Homosapiens″/db_xref＝″taxon:9606″/chromosome＝″20″/map＝″20p11.21″Protein 1..652/product＝″complement component 1，q subcompontent，receptor1″/note＝″complement component C1q receptor″Region 32..130/region_name＝″smart00034，CLECT，C-type lectin(CTL)orcarbohydrate-recognition domain(CRD)；Many of these domains function ascalcium-dependent carbohydrate binding modules″Region 47..128/region_name＝″pfam00059，lectin_c，Lectin C-type domain.This familyincludes both long and short form C-type″Region 385..426/region_name＝″smart00179，EGF_CA，Calcium-binding EGF-like domain″CDS 1..652/gene＝″C1QR1″/coded_by＝″NM_012072.2:149..2107″/note＝″Clq/MBL/SPAreceptor″/db_xref＝″LocusID:22918″/db_xref＝″MIM:120577″ORIGIN 1 matsmgllll llllltqpga gtgadteavv cvgtacytah sgklsaaeaq nhcnqnggnl61 atvkskeeaq hvqrvlaqll rreaaltarm skfwiglqre kgkcldpslp lkgfswvggg121 edtpysnwhk elrnsciskr cvsllldlsq pllpnrlpkw segpcgspgs pgsniegfvc181 kfsfkgmcrp lalggpgqvt yttpfqttss sleavpfasa anvacgegdk detqshyflc241 kekapdvfdw gssgplcvsp kygcnfnngg chqdcfeggd gsflcgcrpg frllddlvtc301 asrnpcsssp crggatcvlg phgknytcrc pqgyqldssq ldcvdvdecq dspcaqecvn361 tpggfrcecw vgyepggpge gacqdvdeca lgrspcaqgc tntdgsfhcs ceegyvlage421 dgtqcqdvde cvgpggplcd slcfntqgsf hcgclpgwvl apngvsctmg pvslgppsgp481 pdeedkgeke gstypraata sptrgpegtp katpttsrps lssdapitsa plkmlapsgs
541 sgvwrepsih hataasgpqe paggdssvat qnndgtdgqk lllfyilgtv vaillllala601 lgllvyrkrr akreekkekk pqnaadsysw vperaesram enqysptpgt dcSEQ ID NO8NP_000233 soluble mannose-binding lectin precursor；mannose-binding lectin；mannosebinding protein；Mannose-binding lectin 2，soluble(opsonic defect)[Homo sapiens]gi|4557739|ref|NP_000233.1|[4557739]sig_peptide 1..20mat_peptide 21..248/product＝″soluble mannose-binding lectin″variation 54/allele＝″D″/allele＝″G″/db_xref＝″dbSNP:1800450″variation 57/allele＝″E″/allele＝″G″/db_xref＝″dbSNP:1800451″Region 134..245/region_name＝″smart00034，CLECT，C-type lectin(CTL)orcarbohydrate-recognition domain(CRD)；Many of these domains function ascalcium-dependent carbohydrate binding modules″Region 144..246/region_name＝″pfam00059，lectin_c，Lectin C-type domain.This familyincludes both long and short form C-type″CDS1..248/gene＝″MBL2″/coded_by＝″NM_000242.1:66..812″/db_xref＝″LocusID:4153″/db_xref＝″MIM:154545″ORIGIN 1 mslfpslpll llsmvaasys etvtcedaqk tcpaviacss pgingfpgkd grdgtkgekg61 epgqglrglq gppgklgppg npgpsgspgp kgqkgdpgks pdgdsslaas erkalqtema121 rikkwltfsl gkqvgnkffl tngeimtfek vkalcvkfqa svatprnaae ngaiqnlike181 eaflgitdek tegqfvdltg nrltytnwne gepnnagsde dcvlllkngq wndvpcstsh241 lavcefpiSEQ ID NO9P11 226 Mannose-binding protein C precursor(MBP-C)(MBP1)(Mannan-binding protein)(Mannose-binding lectin)gi|126676|sp|P11226|MABC_HUMAN[126676]source 1..248/organism＝″Homo sapiens″/db_xref＝″taxon:9606″gene 1..248/gene＝″MBL2″/note＝″MBL″Protein 1..248/gene＝″MBL2″/product＝″Mannose-binding protein C precursor″Region 1..20/gene＝″MBL2″/region_name＝″Signal″Region 21..248/gene＝″MBL2″/region_name＝″Mature chain″/note＝″MANNOSE-BINDINGPROTEIN C.″Region 21..41/gene＝″MBL2″/region_name＝″Domain″/note＝″CYS-RICH.″Region 24/gene＝″MBL2″/region_name＝″Variant″/note＝″T-＞A(INCHINESE)./FTId＝VAR_013294.″Region 42..99/gene＝″MBL2″/region_name＝″Domain″/note＝″COLLAGEN-LIKE.″Site 47/gene＝″MBL2″/site_type＝″hydroxylation″Region 52/gene＝″MBL2″/region_name＝″Variant″/note＝″R-＞C(IN 0.05％ OF EUROPEANAND AFRICAN POPULATIONS)./FTId＝VAR_008543.″Region 54/gene＝″MBL2″/region_name＝″Variant″/note＝″G-＞D(IN CAUCASIAN ANDCHINESE POPULATIONS)./FTId＝VAR_004182.″Region 57/gene＝″MBL2″/region_name＝″Variant″/note＝″G-＞E(IN WEST AFRICANPOPULATION)./FTId＝VAR_004183.″Site 73/gene＝″MBL2″/site_type＝″hydroxylation″Site 79/gene＝″MBL2″/site_type＝″hydroxylation″Site 82/gene＝″MBL2″/site_type＝″hydroxylation″Site 88/gene＝″MBL2″/site_type＝″hydroxylation″Region 109/gene＝″MBL2″/region_name＝″Hydrogen bonded turn″Region 110..129/gene＝″MBL2″/region_name＝″Helical region″Region 130/gene＝″MBL2″/region_name＝″Hydrogen bonded turn″Region 132..134/gene＝″MBL2″/region_name＝″Beta-strand region″Region 135..136/gene＝″MBL2″/reqion_name＝″Hydrogen bonded turn″Region 137..147/gene＝″MBL2″/region_name＝″Beta-strand region″Region 148..157/gene＝″MBL2″/region_name＝″Helical region″Region 153..246/gene＝″MBL2″/region_name＝″Domain″/note＝″C-TYPE LECTIN(SHORTFORM).″Bond bond(155，244)/gene＝″MBL2″/bond_type＝″disulfide″Region 158..159/gene＝″MBL2″/region_name＝″Hydrogen bonded turn″Region 161..162/gene＝″MBL2″/region_name＝″Beta-strand region″Region 168..177/gene＝″MBL2″/region_name＝″Helical region″Region 182..187/gene＝″MBL2″/region_name＝″Beta-strand region″Region 192..193/gene＝″MBL2″/region_name＝″Hydrogen bonded turn″Region 196..197/gene＝″MBL2″/region_name＝″Beta-strand region″Region 198..199/gene＝″MBL2″/region_name＝″Hydrogen bonded tLrn″Region 202/gene＝″MBL2″/region_name＝″Beta-strand region″Region 208/gene＝″MBL2″/region_name＝″Beta-strand region″Region 210..211/gene＝″MBL2″/region_name＝″Hydrogen bonded turn″Region 216..218/gene＝″MBL2″/region_name＝″Helical region″Bond bond(222，236)/gene＝″MBL2″/bond_type＝″disulfide″Region 222..225/gene＝″MBL2″/region_name＝″Beta-strand region″Region 227..228/gene＝″MBL2″/region_name＝″Hydrogen bonded turn″Region 231..234/gene＝″MBL2″/region_name＝″Beta-strand region″Region 236..237/gene＝″MBL2″/region_name＝″Hydrogen bonded turn″Region 239..248/gene＝″MBL2″/region_name＝″Beta-strand region″ORIGIN 1 mslfpslpll llsmvaasys etvtcedaqk tcpaviacss pgingfpgkd grdgtkgekg61 epgqglrglq gppgklgppg npgpsgspgp kgqkgdpgks pdgdsslaas erkalqtema121 rikkwltfsl gkqvgnkffl tngeimtfek vkalcvkfqa svatprnaae ngaiqnlike181 eaflgitdek tegqfvdltg nrltytnwne gepnnagsde dcvlllkngq wndvpcstsh241 lavcefpiSEQ ID NO10Q9ET61 Complement component C1q receptor precursor(Complement component 1，qsubcomponent，receptor 1)(C1qRp)(C1qR(p))(C1q/MBL/SPA receptor)(CD93 antigen)(Cellsurface antigen AA4)gi|21541989|sp|Q9ET61|CD93_RAT[21541989]source 1..643/organism＝″Rattus norvegicus″/db_xref＝″taxon:10116″gene 1..643/gene＝″C1QR1″/note＝″CD93；C1QRP2″Protein 1..643/gene＝″C1QR1″/product＝″Complement component C1q receptor precursor″Region 1..23/gene＝″C1QR1″/region_name＝″Signal″/note＝″POTENTIAL.″Region 24..643/gene＝″C1QR1″/region_name＝″Mature chain″/note＝″COMPLEMENTCOMPONENT C1Q RECEPTOR.″Region 24..571/gene＝″C1QR1″/region_name＝″Domain″/note＝″EXTRACELLULAR(POTENTIAL).″Region 31..173/gene＝″C1QR1″/region_name＝″Domain″/note＝″C-TYPE LECTIN″Region 257..298/gene＝″C1QR1″/region_name＝″Domain″/note＝″EGF-LIKE 1.″Bond bond(261，272)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Bond bond(268，282)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Bond bond(284，297)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Region 299..341/gene＝″C1QR1″/region_name＝″Domain″/note＝″EGF-LIKE 2.″Bond bond(303，314)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Bond bond(308，325)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Site 322/gene＝″C1QR1″/site_type＝″glycosylation″/note＝″N-LINKED(GLCNAC...)(POTENTIAL).″Bond bond(327，340)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Region 342..381/gene＝″C1QR1″/region_name＝″Domain″/note＝″EGF-LIKE 3，CALCIUM-BINDING(POTENTIAL).″Bond bond(346，355)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Bond bond(351，364)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Bond bond(366，380)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Region 382..423/gene＝″C1QR1″/region_name＝″Domain″/note＝＝″EGF-LIKE 4，CALCIUM-BINDING(POTENTIAL).″Bond bond(386，397)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY″Bond bond(393，406)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Bond bond(408，422)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Region 417/gene＝″C1QR1″/region_name＝″Conflict″/note＝″E-＞K(IN REF.2).″Region 424..462/gene＝″C1QR1″/region_name＝″Domain″/note＝″EGF-LIKE 5，CALCIUM-BINDING(POTENTIAL).″Bond bond(428，437)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Bond bond(433，446)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Bond bond(448，461)/gene＝″C1QR1″/bond_type＝″disulfide″/note＝″BY SIMILARITY.″Site 498/gene＝″C1QR1″/site_type＝″glycosylation″/note＝″N-LINKED(GLCNAC...)(POTENTIAL).″Region 572..592/gene＝″C1QR1″/region_name＝″Transmembraneregion″/note＝″POTENTIAL.″Region 593..643/gene＝″C1QR1″/region_name＝″Domain″/note＝″CYTOPLASMIC(POTENTIAL).″ORIGIN 1 mvtstgllll lgllgqlwag aaadseavvc egtacytahw gklsaaeaqh rcnenggnla61 tvkseeearh vqealaqllk tkapsetkig kfwiglqrek gkctyhdlpm kgfswvggge121 dttysnwyka skssciskrc vslildlslk phpshlpkwh espcgtpdap gnsiegflck181 fnfkgmcspl alggpgqlty ttpfqattss lkavpfasva nvvcgdeaes ktnyylcket241 tagvfhwgss gplcvspkfg csfnnggcqq dcfeggdgsf rcgcrpgfrl lddlvtcasr301 npcssnpctg ggmchsvpls enytchcprg yqldssqvhc vdidecedsp cdqecintpg361 gfhcecwvgy qssgske6ac edvdectaay spcaqgctnt dgsfycscke gyimsgedst421 qcedideclg npcdtlcint dgsfrcgcpa gfelapngvs ctrgsmfsel parppqkedk481 gdgkestvpl tempgslngs kdvsnraqtt dlsiqsdsst asvpleievs seasdvwldl541 gtylpttsgh sqpthedsvp ahsdsdtdgq klllfyilgt vvaislllal alglliylkr601 kakkeeikek kaqnaadsys wiperaesra penqysptpg tdcSEQ ID NO11NP_006601 mannan-binding lectin se rine protease 2，isoform 1 precursor；MBL-associatedplasma protein of 19 kD；small MBL-associated protein[Homo sapiens]gi|21264363|ref|NP_006601.2|[21264363]sig_peptide 1..15mat_peptide 16..444/product＝″mannan-binding lectin serine protease 2，isoform 1，chain A″Region 28..136/region_name＝″Domain first found in C1r，C1s，uEGF，and bonemorphogenetic protein.″/note＝″CUB″/db_xref＝″CDD:smart00042″Region 28..134/region_name＝″CUB domain″/note＝″CUB″/db_xref＝″CDD:pfam00431″Region 138..180/region_name＝″Calcium-binding EGF-likedomain″/note＝″EGF_CA″/db_xref＝″CDD:smart00179″variation 155/allele＝″H″/allele＝″R″/db_xref＝″dbSNP:2273343″Region 184..295/region_name＝″Domain first found in C1r，C1s，uEGF，and bonemorphogenetic protein.″/note＝″CUB″/db_xref＝″CDD:smart00042″Region 184..293/region_name＝″CUB domain″/note＝″CUB″/db_xref＝″CDD:pfam00431”Region 300..361/region_name＝″Domain abundant in complement controlproteins″/note＝″CCP″/db_xref＝″CDD:smart00032”Region 300..361/region_name＝″Sushi domain(SCRrepeat)″/note＝″sushi″/db_xref＝″CDD:pfam00084″Region 366..430/region_name＝″Domain abundant in complement controlproteins″/note＝″CCP″/db_xref＝″CDD:smart00032″Region 366..430/region_name＝″Sushi domain(SCRrepeat)″/note＝″sushi″/db_xref＝″CDD:pfam00084″variation 377/allele＝″A″/allele＝″V″/db_xref＝″dbSNP:2273346″Region 444..679/region_name＝″Trypsin-like serineprotease″/note＝″Tryp_SPc″/db_xref＝″CDD:smart00020″mat peptide445..686/product＝″mannan-binding lectin serine protease 2，isoform 1，chain B″Region 445..679/region_name＝″Trypsin″/note＝″trypsin″/db_xref＝″CDD:pfam00089″CDS1..686/gene＝″MASP2″/coded_by＝″NM_006610.2:22..2082″/db_xref＝″LocusID:10747″/db_xref＝″MIM:6051 02″ORIGIN 1 mrlltllgll cgsvatplgp kwpepvfgrl aspgfpgeya ndqerrwtlt appgyrlrly61 fthfdlelsh lceydfvkls sgakvlatlc gqestdtera pgkdtfyslg sslditfrsd121 ysnekpftgf eafyaaedid ecqvapgeap tcdhhchnhl ggfycscrag yvlhrnkrtc181 salcsgqvft qrsgelsspe yprpypklss ctysisleeg fsvildfves fdvethpetl241 cpydflkiqt dreehgpfcg ktlphrietk sntvtitfvt desgdhtgwk ihytstaqpc301 pypmappngh vspvqakyil kdsfsifcet gyellqghlp lksftavcqk dgswdrpmpa361 csivdcgppd dlpsgrveyi tgPgvttyka viqysceetf ytmkvndgky vceadgfwts421 skgekslpvc epvcglsart tggriyggqk akpgdfpwqv lilggttaag allydnwvlt481 aahavyeqkh dasaldirmg tlkrlsphyt qawseavfih egythdagfd ndialiklnn541 kvvinsnitp iclprkeaes fmrtddigta sgwgltqrgf lernlmyvdi pivdhqkcta601 ayekppyprg svtanmlcag lesggkdscr gdsggalvfl dseterwfvg givswgsmnc661 geagqygvyt kvinyipwie niisdfSEQ ID NO12NP_631947 mannan-binding lectin serine protease 2，isoform 2 precursor；MBL-associatedplasma protein of 19 kD；small MBL-associated protein[Homo sapiens]gi|21264361|ref|NP_631947.1|[21264361]sig_peptide 1..15mat_peptide 16..185/product＝″mannan-binding lectin serine protease 2，isoform 2″Region 28..136/region_name＝″Domain first found in C1r，C1s，uEGF，and bonemorphogenetic protein.″/note＝″CUB″/db_xref＝″CDD:smart00042″Region 28..134/region_name＝″CUB domain″/note＝″CUB″/db_xref＝″CDD:pfam00431″Region 138..180/region_name＝″Calcium-binding EGF-likedomain″/note＝″EGF_CA″/db_xref＝″CDD:smart00179″variation 155/allele＝″H″/allele＝″R″/db_xref＝″dbSNP:2273343″CDS1..185/gene＝″MASP2″/coded_by＝″NM_139208.1:22..579″/db_xref＝″LocusID:10747″/db_xref＝″MIM:605102″ORIGIN 1 mrlltllgll cgsvatplgp kwpepvfgrl aspgfpgeya ndqerrwtlt appgyrlrly61 fthfdlelsh lceydfvkls sgakvlatlc gqestdtera pgkdtfyslg sslditfrsd121 ysnekpftgf eafyaaedid ecqvapgeap tcdhhchnhl ggfycscrag yvlhrnkrtc181 seqslSEQ ID NO13NP_624302 mannan-binding lectin serine protease 1，isoform 2，precursor；protease，serine，5(mannose-binding protein-associated)；manan-binding lectin serine protease-1；Ra-reactivefactor serine protease p100[Homo sapiens]gi|21264359|ref|NP_624302.1|[21264359]sig_peptide 1..19mat_peptide 20..445/product＝″mannan-binding lectin senine protease 1，isoform 2，chain A″variation 21/allele＝″I″/allele＝″T″/db_xref＝″dbSNP:1062049″Region 23..138/region_name＝″Domain first found in C1r，C1s，uEGF，and bonemorphogenetic protein.″/note＝″CUB″/db_xref＝″CDD:smart00042″Region 23..135/region_name＝″CUB domain″/note＝″CUB″/db_xref＝″CDD:pfam00431″Region 139..181/region_name＝″Calcium-binding EGF-likedomain″/note＝″EGF_CA″/db_xref＝″CDD:smart00179″Region 185..294/region_name＝″CUB domain″/note＝″CUB″/db_xref＝″CDD:pfam00431″Region 190..296/region_name＝″Domain first found in C1r，C1s，uEGF，and bonemorphogenetic protein.″/note＝″CUB″/db_xref＝″CDD:smart00042″variation 235/allele＝″Q″/allele＝″E″/db_xref＝″dbSNP:3203210″variation 258/allele＝″P″/allele＝″A″/db_xref＝″dbSNP:866085″Region 301..362/region_name＝″Domain abundant in complement controlproteins″/note＝″CCP″/db_xref＝″CDD:smart00032″Region 301..362/region_name＝″Sushi domain(SCRrepeat)″/note＝″sushi″/db_xref＝″CDD:pfam00084″Region 367..432/region_name＝″Domain abundant in complement controlproteins″/note＝″CCP″/db_xre＝″CDD:smart00032″Region 367..432/region_name＝″Sushi domain(SCRrepeat)″/note＝″sushi″/db_xref＝″CDD:pfam00084″mat_peptide446..728/product＝″mannan-binding lectin serine protease 1，isoform 2，chain B″Region 449..711/region_name＝″Trypsin-like serineprotease″/note＝″Tryp_SPc″/db_xref＝″CDD:smart00020″Region450..711/region_name＝″Trypsin″/note＝″trypsin″/db_xref＝″CDD:pfam00089″variation 616/allele＝″A″/allele＝″V″/db_xref＝″dbSNP:2461280″Region 661..703/region_name＝″lmmunoglobulin A1protease″/note＝″IGA1″/db_xref＝″CDD:pfam02395″CDS1..728/gene＝″MASP1″/coded_by＝″NM_139125.1:51..2237″/db_xref＝″LocusID:5648″/db_xref＝″MIM:600521″ORIGIN 1 mrwlllyyal cfslskasah tvelnrmfgq iqspgypdsy psdsevtwni tvpdgfrik61 yfmhfnless ylceydyvkv etedqvlatf cgrettdteq tpgqevvlsp gsfmsitfrs121 dfsneerftg fdahymavdv deckeredee lscdhychny iggyycscrf gyilhtdnrt181 crvecsdnlf tqrtgvitsp dfpnpypkss eclytielee gfmvnlqfed ifdiedhpev241 pcpydyikik vgpkvlgpfc gekapepist qshsvlilfh sdnsgenrgw rlsyraagne301 cpelqppvhg kiepsqakyf fkdqvlvscd tgykvlkdnv emdtfqiecl kdgtwsnkip361 tckivdcrap gelehglitf strnnlttyk seikyscqep yykmlnnntg iytcsaqgvw421 mnkvlgrslp tclpecgqps rslpslvkri iggrnaepgl fpwqalivve dtsrvpndkw481 fgsgallsas wiltaahvlr sqrrdttvip vskehvtvyl glhdvrdksg avnssaarvv541 lhpdfniqny nhdialvqlq epvplgphvm pvclprlepe gpaphmlglv agwgisnpnv601 tvdeiissgt rtlsdvlqyv klpvvphaec ktsyesrsgn ysvtenmfca gyyeggkdtc661 lgdsggafvi fddlsqrwvv qglvswggpe ecgskqvygv ytkvsnyvdw vweqmglpqs721 vvepqverSEQ ID NO14NP_001870 mannan-binding lectin serine protease 1，isoform 1，precursor；protease，serine，5(mannose-binding protein-associated)；manan-binding lectin serine protease-1；Ra-reactivefactor serine protease p100[Homo sepiens]gi|21264357|ref|NP_001870.3|[21264357]sig_peptide 1..19mat_peptide 20..448/product＝″mannan-binding lectin serine protease 1，isoform 1，chain A″variation 21/allele＝″I″/allele＝″T″/db_xref＝″dbSNP:1062049″Region 23..138/region_name＝″Domain first found in C1r，C1s，uEGF，and bonemorphogenetic protein.″/note＝″CUB″/db_xref＝″CDD:smart00042″Region 23..135/region_name＝″CUB domain″/note＝″CUB″/db_xref＝″CDD:pfam00431″Region 139..181/region_name＝″Calcium-binding EGF-likedomain″/note＝″EGF_CA″/db_xref＝″CDD:smart00179″Region 185..294/region_name＝″CUB domain″/note＝″CUB″/db_xref＝″CDD:pfam00431″Region 190..296/region_name＝″Domain first found in C1r，C1s，uEGF，and bonemorphogenetic protein.″/note＝″CUB″/db_xref＝″CDD:smart00042″variation 235/allele＝″Q″/allele＝″E″/db_xref＝″dbSNP:3203210″variation 258/allele＝″P″/allele＝″A″/db_xref＝″dbSNP:866085″Region 301..362/region_name＝″Domain abundant in complement controlproteins″/note＝″CCP″/db_xref＝″CDD:smart00032″Region 301..362/region_name＝″Sushi domain(SCRrepeat)″/note＝″sushi″/db_xref＝″CDD:pfam00084″Region 367..432/region_name＝″Domain abundant in complement controlproteins″/note＝″CCP″/db_xref＝″CDD:smart00032″Region 367..432/region_name＝″Sushi domain(SCRrepeat)″/note＝″sushi″/db_xref＝″CDD:pfam00084″Region 448..691/region_name＝″Trypsin-like serineprotease″/note＝″Tryp_SPc″/db_xref＝″CDD:smart00020″mat_peptide449..699/product＝″mannan-binding lectin serine protease 1，isoform 1，chain B″Region 449..691/region_name＝″Trypsin″/note＝″trypsin″/db_xref＝″CDD:pfam00089″Region 644..675/region_name＝″lmmunoglobulin A1protease″/note＝″IGA1″/db_xref＝″CDD:pfam02395″CDS1..699/gene＝″MASP1″/coded_by＝″NM_001879.3:51..2150″/db_xref＝″LocusID:5648″/db_xref＝″MIM:600521″ORIGIN 1 mrwlllyyal cfslskasah tvelnnmfgq iqspgypdsy psdsevtwni tvpdgfrikl61 yfmhfnless ylceydyvkv etedqvlatf cgrettdteq tpgqevvlsp gsfmsitfrs121 dfsneerftg fdahymavdv deckeredee lscdhychny iggyycscrf gyilhtdnrt181 crvecsdnlf tqrtgvitsp dfpnpypkss eclytielee gfmvnlqfed ifdiedhpev241 pcpydyikik vgpkvlgpfc gekapepist qshsvlilfh sdnsgenrgw rlsyraagne301 cpelqppvhg kiepsqakyf fkdqvlvscd tgykvlkdnv emdtfqiecl kdgtwsnkip361 tckivdcrap gelehgliif strnnlttyk seikyscqep yykmlnnntg iytcsaqgvw421 mnkvlgrslp tclpvcglpk fsrklmarif ngrpaqkgtt pwiamlshln gqpfcggsll481 gsswiviaah clhqsldped ptlrdsdlls psdfkiilgk hwrlrsdene qhlgvkhttl541 hpqydpntfe ndvalvelle spvlnafvmp iclpegpqqe gamvivsgwg kqflqrfpet601 lmeieipivd hstcqkayap lkkkvtrdmi cagekeggkd acagdsggpm vtlnrergqw661 ylvgivswgd dcgkkdrygv ysyihhnkdw iqrvtgvrnSEQ ID NO15XP_122683 similar to mannose binding lectin，liver(A)[Mus musculus]gi|20872845|ref|XP_122683.1|[20872845]source 1..239/organism＝″Musmusculus″/strain＝″C57BL/6J″/db_xref＝″taxon:10090″/chromosome＝″14″Protein 1..239/product＝″similar to mannose binding lectin，liver(A)″Region 126..236/region_name＝″C-type leciin(CTL)or carbohydrate-recognition domain(CRD)″/note＝″CLECT″/db_xref＝″CDD:smartO0034″Region 135..237/region_name＝″Lectin C-typedomain″/note＝″leciin_c″/db_xref＝″CDD:pfam00059”CDS1..239/gene＝″Mbl1″/coded_by＝″XM_122683.1:10..729″/db_xref＝″LocusID:17194″/db_xref＝″MGD:96923″ORIGIN 1 mlllpllpvl lcvvsvsssg sqtcedilki csviacgrdg rdgpkgekge pgqglrglqg61 ppgklgppgs vgspgspgpk gqkgdhgdnr xxxxxxxxxx xxxxxxxxxx xxxxxxhafs121 mgkksgkklf vtnhekmpfs kvkslctelq gtvaiprnae enkaiqevat giaflgitde181 ategqfmyvt ggrltysnwk kdepnnhgsg edcviildng lwndiscqas fkavcefpaSEQ ID NO16AAM21196 C-type mannose-binding lectin[Oncorhynchus mykiss]gi[20385163|gb|AAM21196.1|AF363271_1[20385163]source 1..185/organism＝″Oncorhynchus mykiss″/db_xref＝″taxon:8022″Protein 1..185/product＝″C-type mannose-binding lectin″CDS 1..185/gene＝″MBL″/coded_by＝″AF363271.1:25..582″ORIGIN 1 meklaillll sasialgdan ltqllglepl lktkveqttp eaqveavqeg ikegscpsdw61 ytygshcfkf vsiqqsfvds eqnclalggn lasvhslley qfmqaltkda nghlhstwlg121 gfdaikegtw mwsdgsrfdy tnwdtdepnn agegedclhm neasaklwfd vpcewkfasl181 csrrmSEQ ID NO17AAD45377 mannose-binding lectin[Sus scrofa]gi|5566370|gb|AAD45377.1|AF164576_1[5566370]source 1..240/organism＝″Sus scrofa″/db_xref＝″taxon:9823″/tissue_type＝″liver″Protein 1..240/product＝″mannose-binding lectin″CDS 1..240/coded_by＝″AF164576.1:1..723″ORIGIN 1 mslfpslhll llivmtasht etencediqn tclviscdsp ginglpgkdg ldgakgekge61 pgqgliglqg lpgmvgpqgs pgipglpglk gqkgdsgidp gnslanlrse ldnikkwlif121 aqgkqvgkkl yltngkkmsf ngvkalcaqf qasvatptns renqaiqela gteaflgitd181 eytegqfvdl tgkrvryqnw ndgepnnads aehcveilkd gkwndifcss qlsavcefpaSEQ ID NO18NP_034905 mannose binding lectin，liver(A)[Mus musculus]gi|6754654|ref|NP_034905.1|[6754654]source 1..239/organism＝″Musmusculus″/db_xref＝″taxon:10090″/chromosome＝″14″/map＝″14 15.0 cM″Protein 1..239/product＝″mannose binding lectin，liver(A)″misc_feature 19..239/partial/note＝″mature protein based on homology to rat MPB-A″Region 126..236/region_name＝″C-type lectin(CTL)or carbohydrate-recognition domain(CRD)″/note＝″CLECT″/db_xref＝″CDD:smart00034″Region 135..237/region_name＝″Lectin C-typedomain″/note＝″lectin_c″/db_xref＝″CDD:pfam00059″CDS1..239/gene＝″Mbl1″/coded_by＝″NM 010775.1:121..840″/db_xref＝″LocusID:17194″/db_xref＝″MGD:96923″ORIGIN 1 mlllpllpvl lcvvsvsssg sqtcedtlkt csviacgrdg rdgpkgekge pgqglrglqg61 ppgklgppgs vgspgspgpk gqkgdhgdnr aieeklanme aeirilkskl qltnklhafs121 mgkksgkklf vtnhekmpfs kvkslctelq gtvaiprnae enkaiqevat giaflgitde181 ategqfmyvt ggrltysnwk kdepnnhgsg edcviildng lwndiscqas fkavcefpaSEQ ID NO19NP_034906 mannose binding lectin，serum(C)[Mus musculus]gi|6754656|ref|NP_034906.1|[6754656]source 1..244/organism＝″Musmusculus″/strain＝″BALB/c″/sub_species＝″domesticus″/db_xref＝″taxon:10090″/chromosome＝″19″/map＝″19 25.0 cM″/clone＝″a10″/tissue_type＝″liver″/clone_lib＝″lambda gt10″Protein 1..244/product＝″mannose binding lectin，serum(C)″sig_peptide 1..18Region 120..241/region_name＝″C-type lectin(CTL)or carbohydrate-recognition domain(CRD)″/note＝″CLECT″/db_xref＝″CDD:smart00034″Region 140..242/region_name＝″Lectin C-typedomain″/note＝″lectin_c″/db_xref＝″CDD:pfam00059″CDS 1..244/gene＝″Mbl2″/coded_by＝″NM_010776.1:177..911″/note＝″polysaccharide-bindingcomponent of RaRF；sequence similarity to mannose-bindingproteins″/db_xref＝″LocusID:17195″/db_xref＝″MGD:96924″ORIGIN 1 msiftsflll cvvtvvyaet ltegvqnscp vvtcsspgln gfpgkdgrdg akgekgepgq61 glrglqgppg kvgptgppgn pglkgavgpk gdrgdraefd tseidseiaa lrselralrn121 wvlfslsekv gkkyfvssvk kmsldnvkal csefqgsvat prnaeensai qkvakdiayl181 gitdvrvegs fedltgnrvr ytnwndgepn ntgdgedcvv ilgngkwndv pcsdsflaic241 efsdSEQ ID NO20AAL14428 dendritic cell-specific ICAM-3 grabbing nonintegrin[Macaca nemestrina]gi|16118455|gb|AAL14428.1|AF343727_1[16118455]source 1..381/organism＝″Macaca nemestrina″/db_xref＝″taxon:9545″/cell_tvpe＝″peripheralblood-derived dend ritic cells″Protein 1..381/product＝″dendritic cell-specific ICAM-3 grabbingnonintegrin″/name＝″membrane-associated mannose binding lectin″CDS 1..381/coded_by＝″AF343727.1:1..1146″/note＝″DC-SIGN″ORIGIN 1 msdskeprlq qldlleeeql ggvgfrqtrg ykslagclgh gplvlqllsf tllagllvqv61 skvpsslsqg qskqdaiyqn ltqlkvavse lsekskqqei yqeltrlkaa vgelpekskq121 qeiyeeltrl raavgelpek sklqeiyqel trlkaavgel pekskqqeiy qelsrlkaav181 gdlpekskqq eiyqkltqlk aavdglpdrs kqqeiyqeli qlkaaverlc hpcpwewtff241 qgncyfmsns qrnwhdsita cqevgaqlvv iksaeeqnfl qlqssrsnrf twmglsdlnh301 egtwqwvdgs pllpsfkqyw nkgepnnvge edcaefsgng wnddkcnlak fwickksaas361 csgdeerlls papttpnppp aSEQ ID NO21AAF63470 mannose binding-like lectin precursor[Carassius auratus]gi|7542474|gb|AAF63470.1|AF227739_1[7542474]source 1..246/organism＝″Carassius auratus″/db_xref＝″taxon:7957″/tissue_type＝″liver″Protein＜1..246/product＝″mannose binding-like lectin precursor″/name＝″collectin″sig_peptide＜1..13Region 14..25/region_name＝″N-terminal segment″Region 26..93/region_name＝″collagen-like structure″Region 60..63/region_name＝″break in collagen structure″Region94..124/region_name＝″neck region″Region 125..246/region_name＝″carbohydrate recognition domain″/note＝″CRD″CDS 1..246/gene＝″MBL″/coded_by＝″AF227739.1:＜1..742″/note＝″collectin with structuralhomology to mannose-binding lectin but with a predicted carbohydrate specificity forgalactose″ORIGIN 1 llllqfalql ldgaepqnln cpayggvpgt pghnglpgrd grdgkdgaig pkgekgesgv61 svqgppgkag ppgtagekge rgpsgpqgsp gsesvleslk seiqqlkaki atfekvssvc121 hfrkvgqkyy itdgvvgnfd qglkscmefg gtmvsprtsa enqallklvv ssglgskkpy181 igvtdrkteg qfvdtegkql tftnwgpgqp ddykglqdcg viedtglwdd ggcgdirpim241 ceidikSEQ ID NO22AAF63469 mannose binding-like lectin precursor[Danio rerio]gi|7542472|gb|AAF63469.1|AF227738_1[7542472]sig_peptide 1..23mat_peptide 24..251/product＝″mannose binding-like lectin″Region 24..36/region_name＝″N-terminal segment″Region 37..101/region_name＝″collagen-like structure″Region 71..74/region_name＝″break in collagen structure″Region 102..132/region_name＝″neck region″Region 133..251/region_name＝″carbohydrate recognition domain″/note＝″CRD″CDS 1..251/gene＝″mbl″/coded_by＝″AF227738.1:68..823″/note＝″collectin with structuralhomology to mannose-binding lectin but with a predicted carbohydrate specificity forgalactose″ORIGIN 1 mallklflga llllqlvlql magaadpqsl ncpayagvpg tpghnglpgr dgrvgrdgan61 gpkgekgepg vnvqgppgka gppgpagakg ergpsglpgq dcmsdslkse lqklsdkial121 iekvvnfktf kkvgqkyyvt ddveetfdkg mqycssngga lvlprtleen allkvfvssa181 fkrlfiritd rekegefvdt drkkltftnw gpnqpdnykg aqdcgaiads glwddvscds241 lypiiceiei kSEQ ID NO23AAF63468 mannose binding-like lectin precursor[Cyprinus carpio]gi|7542470|gb|AAF63468.1|AF227737_1[7542470]sig_peptide 1..23mat_peptide 24..256/product＝″mannose binding-like lectin″Region 24..35/region_name＝″N-terminal segment″Region 36..103/region_name＝″collagen-like structure″Region 70..73/region_name＝″break in collagen structure″Region 104..134/region_name＝″neck region″Region 135..256/region_name＝″carbohydrate recognition domain″/note＝″CRD″CDS 1..256/gene＝″MBL″/coded_by＝″AF227737.1:67..837″/note＝″collsctin with structuralhomology to mannose-binding lectin but with a predicted carbohydrate specificity forgalactose″ORIGIN 1 malfklflgt llllqfalql ldgaepqnln cpayggvpgt pghnglpgrd grdgkdgaig61 pkgekgesgv svqgppgkag ppgpagekge rgptgsqgsp gsesvleslk seiqqlkaki121 atfekvasvg hfrqvgqkyy itdgvvgtfd qglkfckdfg gtmvfprtsa enqallklvv181 ssglsskkpy igvtdreteg rfvntegkql tftnwgpgqp ddykglqdcg viedsglwdd241 gscgdirpim ceidnkSEQ ID NO24AAF21018 mannose-binding lectin 2[Sus scrofa]gi|6644342|gb|AAF21018.1AF208528_1[6644342]source 1..31/organism＝″Susscrofa″/db_xref＝″taxon:9823″/chromosome＝″14″/map＝″between S0007 and Sw210″Protein<1..>31/product＝″mannose-binding lectin 2″/name＝″MBL2″CDS 1..31/gene＝″MBL2″/coded_by＝″join(AF208528.1:<..25，AF208528.1:703..>771)″ORIGIN 1 tkgekgepgp gfrgsqgppg kmgppgnige tSEQ ID NO25AAK30298 mannose-binding lectin precursor protein[Gallus gallus]gi|13561409|gb|AAK30298.1|[13561409]sig_peptide 1..21mat_peptide 22..254/product＝″mannose-binding lectin protein″Region 22..46/region name＝″N-terminal segment″Region 47..102/region_name＝″collagen-like″Region 66/region_name＝″break in collagen-like structure″Region 103..139/region_name＝″neck region″Region 140..254/region_name＝″carbohydrate recognition domain；CRD″CDS 1..254/coded_by＝″AF231714.1:242..1006″ORIGIN 1 mtllqpfsal llclslmmat sllttdkpee kmyscpiiqc sapavnglpg rdgrdgpkge61 kgdpgeglrg lqglpgkagp qglkgevgpq gekgqkgerg ivvtddlhrq itdleakirv121 leddlsrykk alslkdvvnv gkkmfvstgk kynfekgksl cakagsvlas prneaental181 kdlidpssqa yigisdaqte grfmylsggp ltysnwkpge pnnhknedca viedsgkwnd241 ldcsnsnifi icelSEQ ID NO26LNMSMC mannose-bin ding lectin C precursor-mouse gi|7428747|pir||LNMSMC[7428747]FEATURES Location/Qualifiers source 1..244/organism＝″Musmusculus″/db_xref＝″taxon:10090″Protein 1..244/product＝″mannose-binding lectin C precursor″/note＝″Ra-reactive factor P28a″Region 1..18/region_name＝″domain″/note＝″signal sequence″Region 19..244/region_name＝″product″/note＝″mannose-binding lectin C″Bond bond(29)/bond_type＝″disulfide″/note＝″interchain″Bond bond(34)/bond_type＝″disulfide″/note＝″interchain″Region 38..94/region_name＝″region″/note＝″collagen-lie″Site 69/site_type＝″modified″/note＝″4-hydroxyproline(Pro)″Region 124..240/region_name＝″domain″/note＝″C-type lectin homology#label LCH″ORIGIN 1 msiftsflll cvvtvvyaet ltegvqnscp vvtcsspgln gfpgkdgrdg akgekgepgq61 glrglqgppg kvgptgppgn pglkgavgpk gdrgdraefd tseidseiaa lrselralrn121 wvlfslsekv gkkyfvssvk kmsldrvkal csefqgsvat prnaeensai qkvakdiayl181 gitdvrvegs fedltgnrvr ytnwndgepn ntgdgedcvv ilgngkwndv pcsdsflaic241 efsdSEQ ID NO27LNMSMA mannose-binding lectin A precursor-mouse gi|625320|pir||LNMSMA[625320]FEATURES Location/Qualifiers source 1..23g/organism＝″Musmusculus″/db_xref＝″taxon:10090″Protein 1..239/product＝″mannose-binding lectin A precursor″/note＝″Ra-reactive factor P28b；serum mannan-binding protein″Region 1..17/region_name＝″domain″/note＝″signal sequence″Region 18..238/region_name＝″product″/note＝″mannose-binding lectin A″Region 36..88/region_name＝″region″/note＝″collagen-lie″Region 119..235/region_name＝″domain″/note＝″C-type lectin homology#label LCH″ORIGIN 1 mlllpllpvl lcvvsvsssg sqtcedtlkt csviacgrdg rdgpkgekge pgqglrglqg61 ppgklgppgs vgspgspgpk gqkgdhgdnr aieeklanme aeirilkskl qltnklhafs121 mgkksgkklf vtnhekmpfs kvkslctelq gtvaiprnae enkaiqevat giaflgitde181 ategqfmyvt ggrltysnwk kdepnnhgsg edcviildng lwndiscqas fkavcefpaSEQ ID NO28LNRTMA mannose-binding lectin A precursor-rat gi|71975|pir||LNRTMA[71975]FEATURES Location/Qualifiers source 1..238/organism＝″Rattusnorvegicus″/db_xref＝″taxon:10116″Protein 1..238/product＝″mannose-binding lectin A precursor″/note＝″serum mannan-bindingprotein″Region 1..17/region_name＝″domain″/note＝″signal sequence″Region 18..238/region_name＝″product″/note＝″mannose-binding lectin A”Region 36..88/region_name＝″region″/note＝″collagen-like″Site 61/site_type＝″modified″/note＝″4-hydroxyproline(Pro)″Site 67/site_type＝″modified″/note＝″4-hydroxyproline(Pro)″Site 73/site_type＝″modified″/note＝″4-hydroxyproline(Pro)″Site 79/site_type＝″modified″/note＝″lysine derivativa(Lys)(probably 5-hydroxylysine)″Site 82/site_type＝″modified″/note＝″lysine derivative(Lys)(probably 5-hydroxylysine)″Region 85..87/region_name＝″region″/note＝″cell attachment(R-G-D)motif″Region 118..234/region_name＝″domain″/note＝″C-type lectin homology#label LCH″ORIGIN 1 mlllpllvll cvvsvsssgs qtceetlktc sviacgrdgr dgpkgekgep gqglrglqgp61 pgklgppgsv gapgsqgpkg qkgdrgdsra ievklanmea eintlkskle ltnklhafsm121 gkksgkkffv tnhermpfsk vkalcselrg tvaiprnaee nkaiqevakt saflgitdev181 tegqfmyvtg grltysnwkk depndhgsge dcvtivdngl wndiscqash tavcefpaSEQ ID NO29LNRTMC mannose-binding lectin C precursor-rat gi|71974|pir||LNRTMC[71974]FEATURES Location/Qualifiers source 1..244/organism＝″Rattusnorvegicus″/db_xref＝″taxon:10116″Protein 1..244/product＝″mannose-binding lectin C precursor″Region 1..18/region_name＝″domain″/note＝″signal sequence″Region 19..244/region_name＝″product″/note＝″mannose-binding lectin C″Bond bond(29)/bond_type＝″disulfide″/note＝″interchain″Bond bond(34)/bond_type＝″disulfide″/note＝″interchain″Region 38..94/region_name＝″region″/note＝″collagen-like″Site 69/site_type＝″modified″/note＝″4-hydroxyproline(Pro)″Region 124..240/region_name＝″domain″/note＝″C-type lectin homology#label LCH″ORIGIN 1 mslftsflll cvltavyaet ltegaqsscp viacsspgln gfpgkdghdg akgekgepgq61 glrglqgppg kvgpagppgn pgskgatgpk gdrgesvefd ttnidleiaa lrselramrk121 wvllsmsenv gkkyfmssvr rmplnrakal cselqgtvat prnaeenrai qnvakdvafl181 gitdqrtenv fedltgnrvr ytnwnegepn nvgsgencvv lltngkwndv pcsdsflvvc241 efsdSEQ ID NO30LNHUMC mannose-binding lectin precursor-human gi|71973|pir||LNHUMC[71973]FEATURES Location/Qualifiers source 1..248/organism＝″Homosapjens″/db_xref＝″taxon:9606″Protein 1..248/product＝″mannose-binding lectin precursor″/note＝″mannan-binding protein″Region 1..20/region_name＝″domain″/note＝″signal sequence″Region 21..248/region_ame＝″product″/note＝″mannose-binding lectin″Region 42..99/region_name＝″region″/note＝″collagen-like″Site 47/site_type＝″modified″/note＝″4-hydroxyproline(Pro)(partial)″Site 73/site_type＝″modified″/note＝″4-hydroxyproline(Pro)(partial)″Site 79/site_type＝″modified″/note＝″4-hydroxyproline(Pro)(partial)″Site 82/site_type＝″modified″/note＝″4-hydroxyproline(Pro)(partial)″Site 88/site_type＝″modified″/note＝″4-hydroxyproline(Pro)(partial)″Region 128..244/region_name＝″domain″/note＝″C-type lectin homology#label LCH″ORIGIN 1 mslfpslpll llsmvaasys etvtcedaqk tcpaviacss pgingfpgkd grdgtkgekg61 epgqglrglq gppgklgppg npgpsgspgp kgqkgdpgks pdgdsslaas erkalqtema121 rikkwltfsl gkqvgnkffl tngeimtfek vkalcvkfqa svatprnaae ngaiqnlike181 eaflgitdek tegqfvdltg nrltytnwne gepnnagsde dcvlllkngq wndvpcstsh241 lavcefpiSEQ ID NO31BAA86864 complement C1s[Homo sapiens]gi|6407558|dbj|BAA86864.1|[6407558]FEATURES Location/Qualifiers source 1..329/organism＝″Homosapiens″/db_xref＝″taxon:9606″/tissue_type＝″peripheral leukocytes″/clone_lib＝″FIXII″Protein 1..329/product＝″complement C1s″CDS 1..329/coded_by＝″join(AB009076.1:1142..1146，AB009076.1:1703..1910，AB009076.1:2118..2295，AB009076.1:3495..3620，AB009076.1:4328..4527，AB009076.1:5047.5200，AB009076.1:5748..＞5863)″/note＝″This gene consists of total 12exons，the last 4 exons of which were reported by Toshi，M.et al.(J.Mol.Biol.208:709-714，1989)ORIGIN 1 mwcivlfsll awvyaeptmy geilspnypq aypseveksw dievpegygi hlyfthldie61 lsencaydsv qijsgdteeg ricgqrssnn phspiveefq vpynklqvif ksdfsneerf121 tgfaayyvat dinectdfvd vpcshfcnnf iggyfcscpp eyflhddmkn cgvncsgdvf181 taligeiasp nypkpypens rceyqirlek gfqvvvtlrr edfdveaads agncldslvf241 vagdrqfgpy cghgfpgpln ietksnaldi ifqtdltgqk kgwklryhgd pmpcpkedtp301 nsvwepakak yvfrdvvqit cldgfevveSEQ ID NO32CAB56124 mannose-binding lectin[Homo sapiens]gi|5911809|emb|CAB56124.1|[5911809]FEATURES Location/Qualifiers source 1..248/organism＝ ″Homosapiens″/db_xref＝″taxon:9606″/chromosome＝″10″/map＝″10q11.2-q21″/note＝″MBLhaplotype HYPD″Protein 1..248/product＝″mannose-binding lectin″sig_peptide 1..20CDS 1..248/gene＝″MBL″/coded_by＝″Y16582.1:892..1638″ORIGIN 1 mslfpslpll llsmvaasys etvtcedaqk tcpaviacss pgingfpgkd gcdgtkgekg61 epgqglrglq gppgklgppg npgpsgspgp kgqkgdpgks pdgdsslaas erkalqtema121 rikkwltfsl gkqvgnkffl tngeimtfek vkalcvkfqa svatprnaae ngaiqnlike181 eaflgitdek tegqfvdltg nrltytnwne gepnnagsde dcvlllkngq wndvpcstsh241 lavcefpiSEQ ID NO33CAB56123 mannose-binding lectin[Homo sapiens]gi|5911807|emb|CAB56123.1|[5911807]FEATURES Location/Qualifiers source 1..248/organism＝″Homosapiens″/db_xref＝″taxon:9606″/chromosome＝″10″/map＝″10q11.2-q21″/note＝″MBLhaplotype HYPA″Protein 1..248/product＝″mannose-binding lectin″sig_peptide 1..20CDS 1..248/gene＝″MBL″/coded_by＝″Y16581.1:892..1638″ORIGIN 1 mslfpslpll llsmvaasys etvtcedaqk tcpaviacss pgingfpgkd grdgtkgekg61 epgqglrglq gppgklgppg npgpsgspgp kgqkgdpgks pdgdsslaas erkalqtema121 rikkwltfsl gkqvgnkffl tngeimtfek vkalcvkfqa svatprnaae ngaiqnlike181 eaflgitdek tegqfvdltg nrltytnwne gepnnagsde dcvlllkngq wndvpcstsh241 lavcefpiSEQ ID NO34CAB56122 mannose-binding lectin[Homo sapiens]gi|5911798|emb|CAB56122.1|[5911798]FEATURES Location/Qualifiers source 1..248/organism＝″Homosapiens″/db_xref＝″taxon:9606″/chromosome＝″10″/map＝″10q11.2-q21″/note＝″MBLhaplotype LXPA″Protein 1..248/product＝″mannose-binding lectin″sig_peptide 1..20CDS 1..248/gene＝″MBL″/coded_by＝″Y16580.1:892..1638″ORIGIN 1 mslfpslpll llsmvaasys etvtcedaqk tcpaviacss pgingfpgkd grdgtkgekg61 epgqglrglq gppgklgppg npgpsgspgp kgqkgdpgks pdgdsslaas erkalqtema121 rikkwltfsl gkqvgnkffl tngeimtfek vkalcvkfqa svatprnaae ngaiqnlike181 eaflgitdek tegqfvdltg nrltytnwne gepnnagsde dcvlllkngq wndvpcstsh241 lavcefpiSEQ ID NO35CAB56121 mannose-binding lectin[Homo sapiens]gi|5911796|emb|CAB56121.1|[15911796]FEATURES Location/Qualifiers source 1..248/organism＝″Homosapiens″/db_xref＝″taxon:9606″/chromosome＝″10″/map＝″10q11.2-q21″/note＝″MBLhaplotype LYPB″Protein 1..248/product＝″mannose-binding lectin″sig_peptide 1..20CDS 1..248/gene＝″MBL″/coded_by＝″Y16579.1:892..1638″ORIGIN 1 mslfpslpll llsmvaasys etvtcedaqk tcpaviacss pgingfpgkd grddtkgekg61 epgqglrglq gppgklgppg npgpsgspgp kgqkgdpgks pdgdsslaas erkalqtema121 rikkwltfsl gkqvgnkffl tngeimtfek vkalcvkfqa svatprnaae ngaiqnlike181 eaflgitdek tegqfvdltg nrltytnwne gepnnagsde dcvlllkngq wndvpcstsh241 lavcefpiSEQ ID NO36CAB56045 mannose-binding lectin[Homo sapiens]gi|5911794|emb|CAB56045.1|[5911794]/organism＝″Homosapiens″/db_xref＝″taxon:9606″/chromosome＝″10″/map＝″10q11.2-q21″/note＝″MBLhaplotype LYQC″Protein 1..248/product＝″mannose-binding lectin″sig_peptide 1..20CDS 1..248/gene＝″MBL″/coded_by＝″Y16578.1:886..1632″ORIGIN 1 mslfpslpll llsmvaasys etvtcedaqk tcpaviacss pgingfpgkd grdgtkeekg61 epgqglrglq gppgklgppg npgpsgspgp kgqkgdpgks pdgdsslaas erkalqtema121 rikkwltfsl gkqvgnkffl tngeimtfek vkalcvkfqa svatprnaae ngaiqnlike181 eaflgitdek tegqfvdltg nrltytnwne gepnnagsde dcvlllkngq wndvpcstsh241 lavcefpiSEQ ID NO37CAB56120 mannose-binding lectin[Homo sapiens]gi|5911792|emb|CAB56120.1|[5911792]FEATURES Location/Qualifiers source 1..248/organism＝″Homosapiens″/db_xref＝″taxon:9606″/chromosome＝″10″/map＝″10q11.2-q21″/note＝″MBLhaplotype LYPA″Protein 1..248/product＝″mannose-binding lectin″sig_peptide 1..20CDS 1..248/gene＝″MBL″/coded_by＝″Y16577.1:892..1638″ORIGIN 1 mslfpslpll llsmvaasys etvtcedaqk tcpaviacss pgingfpgkd grdgtkgekg61 epgqglrglq gppgklgppg npgpsgspgp kgqkgdpgks pdgdsslaas erkalqtema121 rikkwltfsl gkqvgnkffl tngeimtfek vkalcvkfqa svatprnaae ngaiqnlike181 eaflgitdek tegqfvdltg nrltytnwne gepnnagsde dcvlllkngq wndvpcstsh241 lavcefpiSEQ ID NO38CAB56044 mannose-binding lectin[Homo sapiens]gi|5911790|emb|CAB56044.1|[5911790]FEATU RES Location/Qualifiers source 1..248/organism＝″Homosapiens″/db_xref＝″taxon:9606″/chromosome＝″10″/map＝″10q11.2-q21″/note＝″MBLhaplotype LYQA″Protein 1..248/product＝″mannose-binding lectin″sig_peptide 1..20CDS 1..248/gene＝″MBL″/coded_by＝″Y16576.1:886..1632″ORIGIN 1 mslfpslpll llsmvaasys etvtcedaqk tcpaviacss pgingfpgkd grdgtkgekg61 epgqglrglq gppgklgppg npgpsgspgp kgqkgdpgks pdgdsslaas erkalqtema121 rikkwltfsl gkqvgnkffl tngeimtfek vkalcvkfqa svatprnaae ngaiqnlike181 eaflgitdek tegqfvdltg nrltytnwne gepnnagsde dcvlllkngq wndvpcstsh241 lavcefpiSEQ ID NO39AAB53110 C1qR(p)[Homo sapiens]gi|2052498|gb|AAB53110.1|[2052498]FEATURES Location/Qualifiers source 1..652/organism＝″Homosapiens″/db_xref＝″taxon:9606″/cell_line＝″U937 histiocytic cell line″Protein 1..652/product＝″C1qR(p)″/function＝″mediates enhanced phagocytosis by humanmonocytes and macrophages in response to complement C1q，mannose binding lectin(MBL)and pulmonary surfactant protein A(SPA)″CDS 1..652/coded_by＝″U94333.1:149..2107″/note＝″Clq/MBL/SPA receptor″ORIGIN 1 matsmgllll llllltqpga gtgadteavv cvgtacytah sgklsaaeaq nhcnqnggnl61 atvkskeeaq hvqrvlaqll rreaaltarm skfwiglqre kgkcldpslp lkgfswvggg121 edtpysnwhk elrnsciskr cvsllldlsq pllpnrlpkw segpcgspgs pgsniegfvc181 kfsfkgmcrp lalggpgqvt yttpfqttss sleavpfasa anvacgegdk detqshyflc241 kekapdvfdw gssgplcvsp kygcnfnngg chqdcfeggd gsflcgcrpg frllddlvtc301 asrnpcsssp crggatcvlg phgknytcrc Pqgyqldssq ldcvdvdecq dspcaqecvn361 tpggfrcecw vgyepggpge gacqdvdeca lgrspcaqgc tntdgsfhcs ceegyvlage421 dgtqcqdvde cvgpggplcd slcfntqgsf hcgclpgwvl apngvsctmg pvslgppsgp481 pdeedkgeke gstvpraata sptrgpegtp katpttsrps lssdapitsa plkmlapsgs541 sgvwrepsih hataasgpqe paggdssvat qnndgtdgqk lllfyilgtv vaillllala601 lgllvyrkrr akreekkekk pqnaadsysw vperaesram enqysptpgt dcSEQ ID NO40NP_571645 mannose binding-like lectin[Danio rerio]gi|18858997|ref|NP_571645.1|[18858997]sig_peptide 1..23mat_peptide 24..251/product＝″mannose binding-like lectin″Region 24..36/region_name＝″N-terminal segment″Region 33..70/region_name＝″Collagen triple helix repeat(20copies)″/note＝″Collagen″/db_xref＝″CDD:pfam01391″Region 33..70/region_name＝″Collagen triple helix repeat(20copies)″/note＝″Collagen″/db_xref＝″CDD:pfam01391″Region 37..101/region_name＝″collagen-like structure″Region 37..70/region_name＝″Collagen triple helix repeat(20copies)″/note＝″Collagen″/db_xref＝″CDD:pfam01391″Region 71..74/region_name＝″break in collagen structure″Region 102..132/region_name＝″neck region″Region 133..251/region_name＝″carbohydrate recognition domain″/note＝″CRD″Region 134..247/region_name＝″C-type lectin(CTL)or carbohydrate-recognition domain(CRD)″/note＝″CLECT″/db_xref＝″CDD:smart00034″Region 146..247/region_name＝″Lectin C-typedomain″/note＝″lectin_c″/db_xref＝″CDD:pfam00059″CDS 1..251/gene＝″mbl″/coded_by＝″NM_131570.1:68..823″/note＝″collectin with structuralhomology to mannose-pinding lectin but with a predicted carbohydrate specificity forgalactose；mannose binding-like lectin″/db_xref＝″LocusID:58091″ORIGIN 1 mallklflga llllqlvlql magaadpqsl ncpayagvpg tpghnglpgr dgrvgrdgan61 gpkgekgepg vnvqgppgka gppgpagakg ergpsglpgq dcmsdslkse lqklsdkial121 iekvvnfktf kkvgqkyyvt ddveetfdkg mqycssngga lvlprtleen allkvfvssa181 fkrlfiritd rekegefvdt drkkltftnw gpnqpdnykg aqdcgaiads glwddvscds241 lypiiceiei kSEQ ID NO41BAA90338 mannose-binding lectin-associated serine protease(MASP)related protein[Cyprinus carpio]gi|6807499|dbj|BAA90338.1|[6807499]FEATURES Location/Qualifiers source 1..118/organism＝″Cyprinuscarpio″/db_xref＝″taxon:7962″Protein 1..118/product＝″mannose-binding lectin-associated serine protease(MASP)relatedprotein″CDS 1..118/gene＝″MRPb″/coded_by＝″join(AB030447.1:＜1.96，AB030447.1:201..319，AB030447.1:436..514，AB030447.1:616..680)″/note＝″MASP-related protein″ORIGIN 1 kiqtgsntvs ilfhsdnsgd nlgwkltyts tgsecsplaa plnghleplq snyifkdhim61 ltcdpgyslr qgdkefehyq iecqrdgkws sdvplckkke sqrrhrslps iltnqils所述第二多肽優(yōu)選包含所述膠原凝集素或所述蛋白的變體或同系物的至少10個(gè)，如至少12個(gè)，例如至少15個(gè)，如至少20個(gè)，例如至少25個(gè)，如至少30個(gè)，例如至少35個(gè)，如至少40個(gè)，例如至少50個(gè)連續(xù)的氨基酸殘基。此類變體或同系物優(yōu)選與所述膠原凝集素至少70％，如80％，例如90％，如95％相同。
優(yōu)選實(shí)施方案中，所述第二多肽序列包含MBL的CRD區(qū)或MBL的頸區(qū)或MBL的膠原蛋白樣區(qū)。更優(yōu)選所述第二多肽包含MBL的頸區(qū)和CRD區(qū)。在更優(yōu)選的實(shí)施方案中，所述第二多肽序列包含MBL的膠原蛋白樣區(qū)，頸區(qū)和CRD區(qū)。MBL如上所限。
優(yōu)選所述第二多肽序列包含至少為圖2所示MBL序列的氨基酸170-200，如至少為圖2所示MBL序列的氨基酸160-200，如至少為圖2所示MBL序列的氨基酸150-200，如至少為圖2所示MBL序列的氨基酸140-200，如至少為圖2所示MBL序列的氨基酸130-200，如至少為圖2所示MBL序列的氨基酸120-200，如至少為圖2所示MBL序列的氨基酸110-200，如至少為圖2所示MBL序列的氨基酸100-200，如至少為圖2所示MBL序列的氨基酸90-200，如至少為圖2所示MBL序列的氨基酸80-200，如至少為圖2所示MBL序列的氨基酸70-200，如至少為圖2所示MBL序列的氨基酸60-200，如至少為圖2所示MBL序列的氨基酸80-228。
優(yōu)選所述第二多肽序列包含SEQ ID.NO 2的氨基酸80-228。
優(yōu)選實(shí)施方案中，所述第二多肽序列能連接至少一個(gè)MASP蛋白，如選自MASP-1，MASP-2和MASP-3的MASP蛋白或其功能同系物或變體。特別是當(dāng)所述第二多肽是融合蛋白的一部分時(shí)，它能夠連接所述至少一個(gè)MASP蛋白。因此，所述第二多肽序列能夠給所述融合蛋白提供激活補(bǔ)體系統(tǒng)的活性。優(yōu)選實(shí)施方案中，所述第二多肽序列包含選自如下的氨基酸序列SEQ ID.NO 2的56-228，SEQ ID.NO 2的55-228，SEQ ID.NO 2的54-228，和SEQ ID.NO 2的50-228。優(yōu)選實(shí)施方案中，所述第二多肽序列具有選自如下的氨基酸序列SEQ ID.NO 2的56-228，SEQ ID.NO 2的55-228，SEQID.NO 2的54-228，和SEQ ID.NO 2的50-228。
另一實(shí)施方案中，所述第二多肽包含所述膠原凝集素的半胱氨酸富集區(qū)，如所述膠原凝集素的N-末端區(qū)。
融合蛋白所述融合蛋白包含相互連接的第一和第二多肽，可選通過(guò)接頭區(qū)連接。優(yōu)選實(shí)施方案中，所述第一多肽序列位于所述融合蛋白的N-末端并且所述第二多肽序列位于C-末端。
所述融合蛋白組成的具體實(shí)例是-融合蛋白，其包含L-ficolin的半胱氨酸富集區(qū)和膠原蛋白樣區(qū)以及MBL的CRD區(qū)。
-融合蛋白，其包含L-ficolin的半胱氨酸富集區(qū)以及MBL的膠原蛋白樣區(qū)，頸區(qū)和CRD區(qū)。
-融合蛋白，其包含H-ficolin的半胱氨酸富集區(qū)和膠原蛋白樣區(qū)以及MBL的CRD區(qū)。
-融合蛋白，其包含H-ficolin的半胱氨酸富集區(qū)以及MBL的膠原蛋白樣區(qū)，頸區(qū)和CRD區(qū)。
-融合蛋白，其包含M-ficolin的半胱氨酸富集區(qū)和膠原蛋白樣區(qū)以及MBL的CRD區(qū)。
-融合蛋白，其包含M-ficolin的半胱氨酸富集區(qū)以及MBL的膠原蛋白樣區(qū)，頸區(qū)和CRD區(qū)。
-融合蛋白，其包含MBL的半胱氨酸富集區(qū)，以及ficolin的CRD區(qū)。
-融合蛋白，其包含MBL的半胱氨酸富集區(qū)以及ficolin的膠原蛋白樣區(qū)，頸區(qū)和CRD區(qū)。
-融合蛋白，其包含L-ficolin的半胱氨酸富集區(qū)和膠原蛋白樣區(qū)以及肺表面活性相關(guān)性-蛋白D的CRD區(qū)。
-融合蛋白，其包含L-ficolin的半胱氨酸富集區(qū)以及肺表面活性相關(guān)性-蛋白D的膠原蛋白樣區(qū)，頸區(qū)和CRD區(qū)。
-融合蛋白，其包含ficolin的半胱氨酸富集區(qū)和膠原蛋白樣區(qū)以及膠原凝集素-43的CRD區(qū)。
-融合蛋白，其包含ficolin的半胱氨酸富集區(qū)以及膠原凝集素-43的膠原蛋白樣區(qū)，頸區(qū)和CRD區(qū)。
包含圖3所示氨基酸序列的融合蛋白或其功能同系物，優(yōu)選由圖3所示氨基酸序列組成的融合蛋白。另一個(gè)實(shí)施方案中，所述融合蛋白具有圖1所示氨基酸1-50的氨基酸序列和圖2所示氨基酸54-228的氨基酸序列。
如上所討論，所述融合蛋白優(yōu)選能夠形成亞基復(fù)合體和亞基復(fù)合體的寡聚體。優(yōu)選所述融合蛋白基本只形成三聚的，四聚的，五聚的和六聚的亞基寡聚體，如三聚的，四聚的，和五聚的亞基寡聚體，如三聚的或四聚的亞基寡聚體，更優(yōu)選基本只有四聚的亞基寡聚體，以便使融合蛋白的組成更均一。
同系物本說(shuō)明書(shū)中，術(shù)語(yǔ)同系物或變體或功能同系物是同義的，其中蛋白的同系物表現(xiàn)出一或更多氨基酸殘基的一或多個(gè)取代，缺失，和/或添加。片段是一個(gè)亞組的同系物，其為所述蛋白的截短物(truncation)。
所述蛋白的同系物可包含一或更多個(gè)保守氨基酸取代，如至少2個(gè)保守氨基酸取代，例如至少3個(gè)保守氨基酸取代，如至少5個(gè)保守氨基酸取代，例如至少10個(gè)保守氨基酸取代，如至少20個(gè)保守氨基酸取代，例如至少50個(gè)保守氨基酸取代如至少75個(gè)保守氨基酸取代，例如至少100個(gè)保守氨基酸取代。本發(fā)明含義中的保守氨基酸取代是指將一組預(yù)定(predetermined)氨基酸中的一個(gè)氨基酸取代為相同預(yù)定組中表現(xiàn)出類似或基本類似性質(zhì)的另一氨基酸。所述預(yù)定組例如極性側(cè)鏈(Asp，Glu，Lys，Arg，His，Asn，Gln，Ser，Thr，Tyr和Cys，)非極性側(cè)鏈(Gly，Ala，Val，Leu，Ile，Phe，Trp，Pro和Met)脂肪族側(cè)鏈(Gly，Ala Val，Leu，Ile)環(huán)狀側(cè)鏈(Phe，Tyr，Trp，His，Pro)芳香族側(cè)鏈(Phe，Tyr，Trp)酸性側(cè)鏈(Asp，Glu)堿性側(cè)鏈(Lys，Arg，His)酰胺側(cè)鏈(Asn，Gln)羥基側(cè)鏈(Ser，Thr)含硫側(cè)鏈(Cys，Met)，和為單氨基-二羧酸或單氨基-單羧基-單酰胺羧酸(monoamino-monocarboxylic-monoamidocarboxylic acid)的氨基酸(Asp，Glu，Asn，Gln)。
可在優(yōu)選蛋白的任何位置引入保守取代。然而，可能也希望引入非-保守取代。非-保守取代應(yīng)導(dǎo)致形成能夠發(fā)揮(exert)與所述蛋白類似功能的蛋白同系物。此類取代可例如i)疏水性截然不同，例如疏水殘基(Val，Ile，Leu，Phe或Met)被親水殘基如Arg，Lys，Trp或Asn取代，或親水殘基如Thr，Ser，His，Gln，Asn，Lys，Asp，Glu或Trp被疏水殘基取代；和/或ii)對(duì)多肽骨架取向(orientation)的影響截然不同，如用其他殘基取代Pro或Gly或使其他殘基被Pro或Gly取代；和/或iii)電荷截然不同，例如帶負(fù)電荷的殘基如Glu或Asp被帶正電荷的殘基如Lys，His或Arg取代(和反之)；和/或iv)空間占位(stericbulk)截然不同，例如占位大的(bulky)殘基如His，Trp，Phe或Tyr被側(cè)鏈較小的殘基，例如Ala，Gly或Ser取代(和反之)。
本發(fā)明另一個(gè)實(shí)施方案涉及優(yōu)選蛋白的同系物，其中所述同系物包含取代的氨基酸，其具有的親水或親疏水(hydropathic)指數(shù)在它所取代的氨基酸的值的+/-2.5以內(nèi)，例如+/-2.3以內(nèi)，如+/-2.1以內(nèi)，例如+/-2.0以內(nèi)，如+/-1.8以內(nèi)，例如+/-1.6以內(nèi)，如+/-1.5以內(nèi)，例如+/-1.4以內(nèi)，如+/-1.3以內(nèi)，例如+/-1.2以內(nèi)，如+/-1.1以內(nèi)，例如+/-1.0以內(nèi)，如+/-0.9以內(nèi)，例如+/-0.8以內(nèi)，如+/-0.7以內(nèi)，例如+/-0.6以內(nèi)，如+/-0.5以內(nèi)，例如+/-0.4以內(nèi)，如+/-0.3以內(nèi)，例如+/-0.25以內(nèi)，如+/-0.2以內(nèi)。
所述親水和親疏水的氨基酸指數(shù)對(duì)于賦予蛋白相互作用生物功能的重要性在本領(lǐng)域已知(Kyte & Doolittle，1982和Hopp，美國(guó)專利4,554,101，每篇引入本文作為參考)。
本文所用的氨基酸親疏水性指數(shù)值是異亮氨酸(+4.5)；纈氨酸(+4.2)；亮氨酸(+3.8)；苯丙氨酸(+2.8)；半胱氨酸/胱氨酸(+2.5)；蛋氨酸(+1.9)；丙氨酸(+1.8)；甘氨酸(-0.4)；蘇氨酸(-0.7)；絲氨酸(-0.8)；色氨酸(-0.9)；酪氨酸(-1.3)；脯氨酸(-1.6)；組氨酸(-3.2)；谷氨酸(-3.5)；谷氨酰胺(-3.5)；天冬氨酸(-3.5)；天冬酰胺(-3.5)；賴氨酸(-3.9)；和精氨酸(-4.5)(Kyte & Doolittle，1982)。
所述氨基酸親水性值為精氨酸(+3.0)；賴氨酸(+3.0)；天冬氨酸(+3.0.+-.1)；谷氨酸(+3.0.+-.1)；絲氨酸(+0.3)；天冬酰胺(+0.2)；谷氨酰胺(+0.2)；甘氨酸(0)；蘇氨酸(-0.4)；脯氨酸(-0.5.+-.1)；丙氨酸(-0.5)；組氨酸(-0.5)；半胱氨酸(-1.0)；蛋氨酸(-1.3)；纈氨酸(-1.5)；亮氨酸(-1.8)；異亮氨酸(-1.8)；酪氨酸(-2.3)；苯丙氨酸(-2.5)；色氨酸(-3.4)(U.S.4,554,101)。
因此，一個(gè)實(shí)施方案中的氨基酸取代可以以它們的疏水性和親水性值和氨基酸側(cè)鏈取代基，包括電荷，大小等等的相對(duì)類似性為基礎(chǔ)?？紤]到多種前述性質(zhì)的舉例氨基酸取代對(duì)本領(lǐng)域技術(shù)人員是公知的，其包括精氨酸和賴氨酸；谷氨酸和天冬氨酸；絲氨酸和蘇氨酸；谷氨酰胺和天冬酰胺；以及纈氨酸、亮氨酸和異亮氨酸。
另外，同系物可包含氨基酸的添加或缺失，例如添加或缺失2-100個(gè)氨基酸，如2-50個(gè)氨基酸，例如2-20個(gè)氨基酸，如2-10個(gè)氨基酸，例如2-5個(gè)氨基酸，如2-3個(gè)氨基酸。然而，添加超過(guò)100個(gè)氨基酸，如添加100-500個(gè)氨基酸也包括在本發(fā)明中。
與優(yōu)選蛋白至少有一些同源性的蛋白，當(dāng)它們與所述優(yōu)選蛋白至少約40％同源或優(yōu)選相同，例如與所述優(yōu)選蛋白例如至少約50％同源或優(yōu)選相同，例如至少約60％同源或優(yōu)選相同，如至少約70％同源或優(yōu)選相同，例如至少約75％同源或優(yōu)選相同，如至少約80％同源或優(yōu)選相同，例如至少約85％同源或優(yōu)選相同，如至少約90％同源或優(yōu)選相同，例如至少92％同源或優(yōu)選相同，如至少94％同源或優(yōu)選相同，例如至少95％同源或優(yōu)選相同，如至少96％同源或優(yōu)選相同，例如至少97％同源或優(yōu)選相同，如至少98％同源或優(yōu)選相同，例如至少99％同源或優(yōu)選相同時(shí)落入本發(fā)明范圍。
優(yōu)選蛋白是包含膠原凝集素和凝集素及其同系物的補(bǔ)體激活蛋白。
膠原凝集素同系物本發(fā)明范圍中，膠原凝集素包括MBL的同系物被理解為任何能夠發(fā)揮與膠原凝集素功能類似的功能并包含一或多個(gè)上述變異的蛋白。特別是，所述功能是通過(guò)結(jié)合一或多個(gè)糖來(lái)激活補(bǔ)體的能力。
本文所用術(shù)語(yǔ)“膠原凝集素的功能同系物”涉及包含預(yù)確定的氨基酸序列的膠原凝集素功能等效物(equivalent)或片段，并且所述同系物被限定為a)包含能單獨(dú)或如上述發(fā)生亞基復(fù)合后，識(shí)別并結(jié)合葡聚糖，脂磷酸聚糖和糖肌醇磷脂(glycoinositol phospholipid)的氨基酸序列的同系物，所述葡聚糖，脂磷酸聚糖和糖肌醇磷脂包含吡喃糖環(huán)中有3-和4-羥基基團(tuán)的糖(即Man，Glc，F(xiàn)uc或GlcNAc)，和/或b)包含能單獨(dú)或當(dāng)如上述發(fā)生亞基復(fù)合后，與凝集素/MBL途徑的組分建立連接，如結(jié)合MASP-1，MASP-2，MASP-3和/或sMAP的氨基酸序列的同系物，所述結(jié)合導(dǎo)致激活凝集素/MBL途徑，和/或c)包含能通過(guò)膠原蛋白樣區(qū)形成兩或多個(gè)亞基的寡聚體結(jié)構(gòu)的氨基酸序列的同系物，其中所述亞基包含具有半胱氨酸富集區(qū)、膠原蛋白樣區(qū)、頸區(qū)和糖識(shí)別區(qū)的三個(gè)相同多肽。
凝集素同系物本發(fā)明范圍中，凝集素包括ficolin的同系物被理解為任何能夠發(fā)揮與凝集素功能類似的功能并包含一或多個(gè)上述變異的蛋白。特別是，所述功能是通過(guò)結(jié)合一或更多個(gè)糖來(lái)激活補(bǔ)體的能力。
本文所用術(shù)語(yǔ)“凝集素的功能同系物”涉及包含預(yù)確定的氨基酸序列的凝集素功能等效物或片段，并且所述同系物被限定為
a)包含單獨(dú)或如上述發(fā)生亞基復(fù)合后，能夠識(shí)別并結(jié)合N-乙酰葡萄糖胺(GlcNAc)，或N-乙酰半乳糖胺(GalNAc)或彈性蛋白的氨基酸序列的同系物，和/或b)包含單獨(dú)或如上述發(fā)生亞基復(fù)合后，能夠與凝集素/MBL途徑的組分建立連接，如結(jié)合MASP-1，MASP-2，MASP-3和/或sMAP的氨基酸序列的同系物，所述結(jié)合導(dǎo)致激活凝集素/MBL途徑，和/或c)包含能夠通過(guò)膠原蛋白樣區(qū)形成兩或多個(gè)亞基的寡聚體結(jié)構(gòu)的氨基酸序列的同系物，其中所述亞基包含具有半胱氨酸富集區(qū)、膠原蛋白樣區(qū)、頸區(qū)和纖維蛋白原樣區(qū)的三個(gè)相同多肽。
凝集素/MBL途徑的激活，即融合蛋白激活補(bǔ)體系統(tǒng)的活性，可通過(guò)評(píng)估所述融合蛋白或亞基復(fù)合體或其寡聚復(fù)合體的C4裂解效應(yīng)來(lái)評(píng)估，后者可以通過(guò)包括如下步驟的方法來(lái)評(píng)估-應(yīng)用(applying)包含預(yù)確定量的融合蛋白以及預(yù)確定量的MASP-1，MASP-2或MASP-3的樣品，-將至少一種補(bǔ)體因子應(yīng)用到所述樣本，-檢測(cè)被裂解的補(bǔ)體因子的量，-使所述被裂解的補(bǔ)體因子量與融合蛋白的量相關(guān)，并-確定所述融合蛋白的活性。
優(yōu)選用于本方法的補(bǔ)體因子是被MBL/MASP-2復(fù)合體裂解的補(bǔ)體因子，如C4。然而，所述補(bǔ)體因子也可選自C3和C5。
所述被裂解的補(bǔ)體因子可用多種手段(means)檢測(cè)，如用針對(duì)所述被裂解的補(bǔ)體因子的抗體檢測(cè)。
在使經(jīng)典補(bǔ)體激活途徑和替代補(bǔ)體激活途徑的干擾最小化或去除的條件下進(jìn)行試驗(yàn)。
優(yōu)選膠原凝集素和/或凝集素的同系物顯示上述功能中的兩種，更優(yōu)選上述功能中的三種。
制備融合蛋白所述融合蛋白可用任何本領(lǐng)域技術(shù)人員公知的合適方法制備。如下描述數(shù)種制備所述融合蛋白的方法，然而本發(fā)明不限于所述方法。
合成制備合適時(shí)，特別是涉及融合蛋白的大小時(shí)，所述融合蛋白可通過(guò)合成來(lái)制備。合成制備肽的方法本領(lǐng)域公知。制備合成肽的具體描述以及實(shí)用的建議可見(jiàn)Synthetic PeptidesA User′s Guide(Advances in Molecular Biology)，GrantG.A.ed.，Oxford University Press，2002或者Pharmaceutical FormulationDevelopment of Peptides and Proteins，F(xiàn)rokjaer and Hovgaard eds.，Taylor andFrancis，1999。
重組制備本發(fā)明融合蛋白優(yōu)選用重組DNA技術(shù)制備。制備編碼融合蛋白每一部分的DNA序列可用DNA酶I根據(jù)標(biāo)準(zhǔn)方案(Sambrook等，Molecular cloningA Laboratory manual.2 rd ed.，CSHL Press，Cold Spring Harbor，NY，1989)將衍生所述融合蛋白部分的全長(zhǎng)蛋白的DNA編碼序列(基因組DNA或cDNA)裂解。然后將所得的編碼所述融合蛋白各個(gè)部分的DNA序列融合到一起。
所述DNA序列也可以通過(guò)聚合酶鏈?zhǔn)椒磻?yīng)用特異性引物來(lái)制備，例如美國(guó)專利4,683,202或Saiki等，1988，Science 239487-491所述。
編碼本發(fā)明融合蛋白的DNA序列可以用已有的標(biāo)準(zhǔn)方法通過(guò)合成來(lái)制備，例如Beaucage和Caruthers，1981，Tetrahedron Lett.221859-1869描述的亞膦酰胺(phosphoamidine)方法，或Matthes等，1984，EMBO J.3801-805描述的方法。根據(jù)亞膦酰胺方法，在例如自動(dòng)DNA合成儀中合成寡核苷酸，純化、退火、連接并克隆到合適的載體中。
然后將所述DNA序列插入重組表達(dá)載體，其可以是任何可方便地進(jìn)行重組DNA操作的載體。選擇載體通常依賴于它要被引入的宿主細(xì)胞。因此，所述載體可以是自主復(fù)制載體，即作為染色體外實(shí)體(entity)存在、且其復(fù)制獨(dú)立于染色體復(fù)制的載體，例如質(zhì)粒?；蛘?，所述載體可以在引入宿主細(xì)胞時(shí)，被整合到宿主細(xì)胞基因組，并與它所整合的染色體一起復(fù)制。
載體中，編碼融合蛋白的DNA序列應(yīng)被可操作性連接到合適的啟動(dòng)子序列。所述啟動(dòng)子可以是在所選擇的宿主細(xì)胞中顯示轉(zhuǎn)錄活性的任何DNA序列，可來(lái)自與所述宿主細(xì)胞同源或不同源的蛋白的編碼基因。指導(dǎo)編碼DNA序列在哺乳動(dòng)物細(xì)胞內(nèi)轉(zhuǎn)錄的合適啟動(dòng)子舉例有SV40啟動(dòng)子(Subramani等，1981，Mol.Cell Biol.1854-864)，MT-1(金屬硫蛋白基因)啟動(dòng)子(Palmiter等，1983，Science 222809-814)或腺病毒2主要晚期啟動(dòng)子。合適用于昆蟲(chóng)細(xì)胞的啟動(dòng)子是多角體(polyhedrin)啟動(dòng)子(Vasuvedan等，1992，F(xiàn)EBS Lett.3117-11)。合適用于酵母宿主細(xì)胞的啟動(dòng)子包括來(lái)自酵母糖酵解基因(Hitzeman等，1980，J.Biol.Chem.25512073-12080；Alber和Kawasaki，1982，J.Mol.Appl.Gen.1419-434)或醇脫氫酶基因(Young等，1982，inGenetic Engineering of Microorganisms for Chemicals，Hollaender等eds.，Plenum Press，New York)，或TPI1(美國(guó)專利4,599,311)或ADH2-4c(Russell等，1983，Nature 304652-654)的啟動(dòng)子。合適用于絲狀真菌宿主細(xì)胞的啟動(dòng)子是，例如，ADH3啟動(dòng)子(McKnight等，1985，EMBO J.42093-2099)或tpiA啟動(dòng)子。
所述DNA編碼序列也可以可操作地與合適的終止子，如人生長(zhǎng)激素終止子(Palmiter等，如前引用)或(用于真菌宿主時(shí))TPI1(Alber和Kawasaki，如前引用)或ADH3(McKnight等，如前引用)啟動(dòng)子連接。該載體還可包含聚腺苷酸化信號(hào)(例如來(lái)自SV 40或腺病毒5 Elb區(qū))，轉(zhuǎn)錄增強(qiáng)子序列(例如SV 40增強(qiáng)子)和翻譯增強(qiáng)子序列(例如編碼腺病毒VARNA的序列)等元件。
所述重組表達(dá)載體還可包含使所述載體在目標(biāo)宿主細(xì)胞中復(fù)制的DNA序列。此種序列舉例(當(dāng)所述宿主細(xì)胞是哺乳動(dòng)物細(xì)胞時(shí))是SV40復(fù)制起點(diǎn)。所述載體也可包含選擇性標(biāo)記物，例如其產(chǎn)物彌補(bǔ)了宿主細(xì)胞的缺陷的基因，如編碼二氫葉酸還原酶(DHFR)的基因或帶有(confer)對(duì)藥物，例如新霉素，潮霉素或氨甲蝶呤的抗性的基因。
本領(lǐng)域技術(shù)人員公知用于連接分別編碼所述融合蛋白、啟動(dòng)子和終止子的DNA序列并將它們插入合適的包含復(fù)制必要信息的載體的方法(參見(jiàn)(cf.)，例如，Sambrook等，如前引用)。
合成所述重組融合蛋白可使用體外或體內(nèi)培養(yǎng)物。宿主細(xì)胞培養(yǎng)物優(yōu)選是真核宿主細(xì)胞培養(yǎng)物。本文中真核細(xì)胞培養(yǎng)物轉(zhuǎn)化是指將重組DNA引入所述細(xì)胞。此方法中用的表達(dá)構(gòu)建體的特征為具有選自哺乳動(dòng)物基因的編碼區(qū)，所述哺乳動(dòng)物基因包括人基因和與非常相似的基因如黑猩猩(chimpanzee)的基因。所用的表達(dá)構(gòu)建體還具有的特征為，啟動(dòng)子區(qū)選自病毒或真核生物，包括哺乳動(dòng)物細(xì)胞和昆蟲(chóng)細(xì)胞的基因。
根據(jù)本發(fā)明制備重組MBL的方法其特征在于，所述宿主細(xì)胞培養(yǎng)物優(yōu)選是真核生物的，例如是哺乳動(dòng)物的細(xì)胞培養(yǎng)物。優(yōu)選的宿主細(xì)胞培養(yǎng)物是人腎細(xì)胞的培養(yǎng)物，更優(yōu)選，宿主細(xì)胞培養(yǎng)物是人胚胎腎細(xì)胞(HEK細(xì)胞)的培養(yǎng)物，如用于制備重組人MBL的HEK 293細(xì)胞系?！癏EK 293細(xì)胞系”指任何源于人胚胎腎組織的細(xì)胞系，例如但不限于在美國(guó)典型培養(yǎng)物保藏中心(American Type Culture Collection)以號(hào)碼CRL-1573和CRL-10852保藏的細(xì)胞系。
其他細(xì)胞可以是雞胚胎成纖維細(xì)胞，倉(cāng)鼠卵巢細(xì)胞，幼倉(cāng)鼠(baby hamster)腎細(xì)胞，人宮頸癌細(xì)胞(cervical carcinoma cell)，人黑素瘤細(xì)胞，人腎細(xì)胞，人臍血管(nmbilical vascular)內(nèi)皮細(xì)胞，人腦內(nèi)皮細(xì)胞，人口腔腫瘤細(xì)胞，猴腎細(xì)胞，小鼠成纖維細(xì)胞，小鼠腎細(xì)胞，小鼠結(jié)締組織細(xì)胞，小鼠寡分支(oligodendritic)細(xì)胞，小鼠吞噬細(xì)胞，小鼠成纖維細(xì)胞，小鼠成神經(jīng)細(xì)胞瘤細(xì)胞，小鼠前B細(xì)胞，小鼠B淋巴細(xì)胞瘤細(xì)胞，小鼠漿細(xì)胞瘤細(xì)胞，小鼠惡性畸胎瘤細(xì)胞，大鼠星形細(xì)胞瘤細(xì)胞，大鼠乳房(mammary)上皮細(xì)胞，COS，CHO，BHK，VERO，HeLa，MDCK，W138和NIH 3T3細(xì)胞。
或者，真菌細(xì)胞(包括酵母細(xì)胞)可用作宿主細(xì)胞。合適的酵母細(xì)胞舉例包括糖酵母(Saccharomyces spp.)或裂殖酵母(Schizosaccharomyces spp.)的細(xì)胞，特別是釀酒酵母(Saccharomyces cerevisiae)的細(xì)胞株。其他真菌細(xì)胞舉例是絲狀真菌，例如曲霉(Aspergillus spp.)或鏈孢霉(Neurospora spp)，特別是米曲霉(Aspergillus oryzae)或黑曲霉(Aspergillus niger)株。曲霉(Aspergillus spp.)用于蛋白表達(dá)的用途見(jiàn)例如EP 238 023描述。
另外，可選擇那些調(diào)控插入序列的表達(dá)、或按所需特定方式修飾并加工基因產(chǎn)物的宿主細(xì)胞株。蛋白產(chǎn)物的這類修飾(例如，糖基化)和加工(例如，裂解)可能對(duì)于所述蛋白的功能是重要的。不同的宿主細(xì)胞對(duì)蛋白和基因產(chǎn)物具有獨(dú)特和特異的翻譯后加工和修飾機(jī)制?？蛇x擇合適的細(xì)胞系或宿主系統(tǒng)來(lái)確保正確修飾并加工所表達(dá)的異源蛋白。為此，可使用具有正確加工初級(jí)轉(zhuǎn)錄物(primary transcript)、糖基化、和磷酸化所述基因產(chǎn)物的細(xì)胞機(jī)制的真核生物宿主細(xì)胞。上面所列的哺乳動(dòng)物細(xì)胞類型屬于可用作合適宿主細(xì)胞的那些。
轉(zhuǎn)染哺乳動(dòng)物細(xì)胞并表達(dá)引入所述細(xì)胞的DNA序列的方法見(jiàn)例如Kaufman和Sharp，J.Mol.Biol.159，1982，pp.601-621；Southern和Berg，1982，J.Mol.Appl.Genet.1327-341；Loyter等，1982，Proc.Natl.Acad.Sci.USA 79422-426；Wigler等，1978，Cell 14725；Corsaro和Pearson，1981，in Somatic CellGenetics 7，p.603；Graham和van der Eb，1973，Virol.52456；和Neumann等，1982，EMBO J.1841-845所述。
其他真核生產(chǎn)系統(tǒng)也被本發(fā)明包括(envisage)，如在轉(zhuǎn)基因植物或動(dòng)物中制備所述融合蛋白。
本發(fā)明另一方面提供了如下制備融合蛋白的方法，其-制備了如上所限編碼融合蛋白的基因表達(dá)構(gòu)建體，-用所述構(gòu)建體轉(zhuǎn)化宿主細(xì)胞培養(yǎng)物，-培養(yǎng)所述宿主細(xì)胞培養(yǎng)物，從而表達(dá)所述多肽并將其分泌到培養(yǎng)基中，之后獲得包含重組融合蛋白的培養(yǎng)基，并純化所述融合蛋白。
用于培養(yǎng)所述細(xì)胞的培養(yǎng)基可以是任何常用的適合哺乳動(dòng)物細(xì)胞生長(zhǎng)的培養(yǎng)基，如含血清或無(wú)血清、包含合適添加物的培養(yǎng)基，或適合昆蟲(chóng)，酵母或真菌細(xì)胞生長(zhǎng)的培養(yǎng)基。合適的培養(yǎng)基可得自商品供應(yīng)商或可用公開(kāi)配方制備(例如見(jiàn)美國(guó)典型培養(yǎng)物保藏中心目錄)。培養(yǎng)基舉例有添加了，例如，胰島素，運(yùn)鐵蛋白，硒和胎牛血清的DMEM或RPMI-1640。
然后可將由細(xì)胞重組制備的融合蛋白從培養(yǎng)基中用常用方法回收，所述方法包括通過(guò)離心或過(guò)濾來(lái)使宿主細(xì)胞與培養(yǎng)基分離，用鹽、例如硫酸銨來(lái)沉淀上清或過(guò)濾物中的蛋白性質(zhì)的組分，用多種層析方法、例如HPLC、離子交換層析、親和層析等來(lái)純化。
優(yōu)選實(shí)施方案中，如上所述用糖親和層析來(lái)純化所述融合蛋白。本發(fā)明優(yōu)選實(shí)施方案中，用適合親和層析的甘露糖，己糖的基質(zhì)或N-乙酰葡萄糖胺衍生的基質(zhì)來(lái)進(jìn)行親和層析。特別是使用那些已將基質(zhì)經(jīng)過(guò)甘露糖衍生的親和層析。
本文中，純化的重組融合蛋白被理解為用例如糖親和層析從細(xì)胞培養(yǎng)物上清或純化的轉(zhuǎn)基因動(dòng)物體液或組織中純化得到的重組融合蛋白。
將所述培養(yǎng)基加載到層析柱中，然后洗柱子，優(yōu)選用非-變性緩沖液洗柱子，所述緩沖液的組成，pH和離子強(qiáng)度導(dǎo)致除去蛋白但不洗脫出融合蛋白。此種緩沖液可以是TBS。用能夠有效洗脫融合蛋白的選擇性解吸附劑，如含有解吸附劑，如EDTA(例如5mM)或甘露糖(例如50mM)的TBS來(lái)洗脫融合蛋白，并收集融合蛋白。
藥物組合物和治療本發(fā)明所獲得的融合蛋白可用于制備預(yù)防和/或治療多種疾病或狀況的藥物組合物。本文術(shù)語(yǔ)“藥物組合物”和“藥物”同義。
除了所述融合蛋白，所述藥物組合物可包含可藥用的載體物質(zhì)和/或賦形劑(vehicle)。
特別可加入穩(wěn)定劑來(lái)穩(wěn)定所述融合蛋白。所述穩(wěn)定劑可以是糖醇(sugaralcohol)，糖(saccharide)，蛋白和/或氨基酸。穩(wěn)定劑舉例可以是清蛋白或麥芽糖。
可例如根據(jù)給藥形式，將其它常用添加劑加入所述藥物組合物。
一個(gè)實(shí)施方案中，所述藥物組合物呈適合注射的形式?？墒褂贸Ｓ幂d體物質(zhì)，如等滲鹽水。
另一個(gè)實(shí)施方案中，所述藥物組合物呈適合肺給藥的形式，如呈吸入粉末或局部給藥的膏劑(creme)或液體的形式。
本文的治療可包含治愈和/或預(yù)防，例如人的免疫系統(tǒng)和生殖系統(tǒng)和其他動(dòng)物中起與此相似的作用的功能單元。要被治療的狀況不一定指現(xiàn)在已知需要治療的狀況，但通常包含任何與現(xiàn)有和/或預(yù)期需要有聯(lián)系或與改善正常狀況有聯(lián)系的狀況。特別是，所述治療是對(duì)凝集素缺乏，如MBL缺乏的狀況的治療。
在本發(fā)明另一方面提供了藥物生產(chǎn)，該藥物由所述融合蛋白的藥物組合物組成，用于治療疾病包括治愈和/或預(yù)防疾病和紊亂(disorder)狀況在內(nèi)的情況，例如人的免疫系統(tǒng)和生殖系統(tǒng)和其他動(dòng)物中起與此相似的作用的功能單元。
需要用本發(fā)明化合物治療的疾病、紊亂和/或狀況包含，例如治療MBL缺乏的狀況，治療癌癥和與免疫抑制性化療相關(guān)的感染，包括特別是那些可見(jiàn)于與癌癥治療或與器官植入和/或移植相關(guān)的感染。本發(fā)明也包含治療與習(xí)慣性流產(chǎn)(recurrent miscarriage)相關(guān)的狀況。
因此，所述藥物組合物特別可用于治療和/或預(yù)防選自如下的臨床狀況感染，MBL缺乏，癌癥，與化療相關(guān)的紊亂，如感染，與人免疫缺陷病毒(HIV)相關(guān)的疾病，與先天或獲得性免疫缺陷有關(guān)的疾病，更具體為慢性炎性脫髓鞘性多發(fā)性神經(jīng)病(inflammatory demyelinating polyneuropathy)(CIDP，多病灶性運(yùn)動(dòng)神經(jīng)病(Multifocal motoric neuropathy)，多發(fā)性硬化，重癥肌無(wú)力(Myasthenia Gravis)，伊-蘭綜合征(Eaton-Lambert’s syndrome)，視神經(jīng)炎(Opticus Neuritis)，癲癇；原發(fā)性抗磷脂綜合征(Primary antiphosholipidsyndrome)；類風(fēng)濕性關(guān)節(jié)炎，系統(tǒng)性紅斑狼瘡，系統(tǒng)性硬皮病(Systemicscleroderma)，脈管炎，韋格納肉芽腫病(Wegner’s granulomatosis)，干燥綜合征(Sigren’s syndrome)，青少年類風(fēng)濕性關(guān)節(jié)炎(Juvenile rheumatiod arthritis)；自身免疫性中性粒細(xì)胞減少癥(Autoimmune neutropenia)，自身免疫溶血性貧血(Autoimmune haemolyric anaemia)，中性粒細(xì)胞減少癥；克隆病(Crohn’sdisease)，潰瘍性結(jié)腸炎(Colitis ulcerous)，腹腔疾病(Coeliac disease)；哮喘，敗血性休克綜合征(Septic shock syndrome)，慢性疲勞綜合征，牛皮癬，中毒性休克綜合征(Toxic shock syndrome)，糖尿病，鼻竇炎(Sinuitis)，擴(kuò)張型心肌病(Dilated cardiomyopathy)，心內(nèi)膜炎，動(dòng)脈粥樣硬化，原發(fā)性低/無(wú)丙種球蛋白血癥(hypo/agammaglobulinaemia)包括普通可變型免疫缺陷病(common variable immunodeficiency)，維-奧綜合征(Wiskot-Aldrich syndrome)和重癥聯(lián)合免疫缺陷病(serve combined immunodefiency)(SCID)，在有慢性淋巴細(xì)胞白血病(CLL)和多發(fā)性骨髓瘤的病人中的繼發(fā)性低/無(wú)丙種球蛋白血癥，急性和慢性特發(fā)性血小板減少性紫癜(ITP)，同種異體骨髓移植(Allogenicbone marrow transferr)(BTM)，Kawasaki’s disease，和吉-巴綜合征(Guillan-Barre’s disease)。
給藥途徑可以是任何合適的途徑，如靜脈內(nèi)，肌肉內(nèi)，皮下或皮內(nèi)途徑。本發(fā)明也包括肺或局部(topical)給藥。
特別是可以給藥所述融合蛋白來(lái)預(yù)防和/或治療病人感染，所述病人患有與先天或獲得性MBL缺陷相關(guān)的臨床癥狀或具有患所述癥狀的危險(xiǎn)。多種多樣的癥狀會(huì)導(dǎo)致MBL-缺陷的個(gè)體對(duì)感染的易感性提高，如化療或其他治療性細(xì)胞毒性治療，癌癥，AIDS，遺傳性傾向(disposition)，慢性感染，和中性粒細(xì)胞減少癥。
因此可在開(kāi)始給予化療等之前和在化療的至少一部分時(shí)間內(nèi)時(shí)，給藥所述藥物組合物一段時(shí)間。
可將所述融合蛋白作為常用的“促進(jìn)劑(booster)”在化療前給藥，或可將它給藥那些只具有患MBL缺陷的危險(xiǎn)的人?？赏ㄟ^(guò)在治療前測(cè)量MBL水平來(lái)確定有風(fēng)險(xiǎn)的那組病人，并且只讓那些MBL水平低于預(yù)確定水平者接受治療。
將所述融合蛋白在化療期以合適劑量方案(regime)給藥，特別是通常以合適間隔給藥，例如，每周一次或兩次。
一般每個(gè)劑量給藥1-100mg，如2-10mg，常常每個(gè)劑量5-10mg。常給藥約0.1mg/kg體重。
本發(fā)明另一方面是本發(fā)明重組組合物在還包括其他藥物的組合試劑盒(kit-of-parts)中的用途。特別是其他藥物可以是抗微生物藥物，如抗生素。
在流產(chǎn)的情況中，已經(jīng)報(bào)道在另外有原因未知的習(xí)慣性流產(chǎn)的病人中，MBL血漿水平低的頻率是增高的，這是為什么在這些病例中希望通過(guò)給藥重組MBL來(lái)重建MBL水平，從而降低了易流產(chǎn)性。
至于本發(fā)明化合物的性質(zhì)，看來(lái)本發(fā)明在最廣泛的范圍內(nèi)涉及能夠用作調(diào)理素，即能夠增強(qiáng)吞噬細(xì)胞攝入的化合物，所述增強(qiáng)要么通過(guò)所述化合物和吞噬細(xì)胞的直接相互作用要么通過(guò)介導(dǎo)在靶表面上的補(bǔ)體沉積。
實(shí)施例實(shí)施例1FCNMBL-r1，-r2，-r3，-r4，-rS，-r6和-r7的質(zhì)粒克隆1.1綜述構(gòu)建一系列質(zhì)粒來(lái)在哺乳動(dòng)物細(xì)胞中表達(dá)重組人甘露糖結(jié)合型凝集素2基因(rhMBL)和人ficolin 2(FCN2)的蛋白融合物。所述載體來(lái)自高拷貝數(shù)的基于ColE1的質(zhì)粒并被設(shè)計(jì)來(lái)在哺乳動(dòng)物系統(tǒng)中表達(dá)蛋白。所述融合蛋白表達(dá)由人巨細(xì)胞病毒(CMV)立即早期啟動(dòng)子驅(qū)動(dòng)來(lái)提高組成型表達(dá)。在細(xì)菌中，通過(guò)受原核β-內(nèi)酰胺酶啟動(dòng)子控制的氨芐青霉素抗性基因使選擇成為可能。新霉素抗性基因通過(guò)SV40早期啟動(dòng)子驅(qū)動(dòng)，它在哺乳動(dòng)物細(xì)胞中提供了用G418進(jìn)行的穩(wěn)定選擇。
1.2構(gòu)建體和實(shí)驗(yàn)工作為表達(dá)Ficolin2和MBL的融合蛋白，我們?cè)O(shè)計(jì)并構(gòu)建了一系列質(zhì)粒。所述新的重組質(zhì)粒是基于以前克隆的pcDNA2001-cintMBLcDNA。此質(zhì)粒包含了合成的內(nèi)含子和人MBL的cDNA。
設(shè)計(jì)了如下融合物(下劃線字體表示FCN2部分-斜體表示融合蛋白的MBL部分)FCN2MBLr1(SEQ ID NO118)FCN2(信號(hào)序列(signalseq)+膠原蛋白+“鉸鏈”到ficolin區(qū)氨基酸(aa)131)MBL(始于氨基酸129糖結(jié)合區(qū)(carbohyd.bind dom.))
MELDRAVGVLGAATLLLSFLGMAWALQAADTCPEVKMVGLEGSDKLTILRGCPGLPGAPGDKGEAGTNGKRGERGPPGPPGKAGPPGPNGAPGEPQPCLTGPRTCKDLLDRGHFLSGWHTIYLPDCRPLTFSLGKQVGNKFFLTNGEIMTFEKVKALCVKFQASVATPRNAAENGAIQNLIKEEAFLGITDEKTEGQFVDLTGNRLTYTNWNEGEPNNAGSDEDCVLLLKNGQWNDVPCSTSHLAVCEFPIFCN2MBLr2(SEQ ID NO119)FCN2(信號(hào)序列+膠原蛋白+“鉸鏈”+包含預(yù)定的(pred.)卷曲螺旋到氨基酸207的ficolin區(qū)部分)MBL(始于氨基酸129糖結(jié)合區(qū))MELDRAVGVLGAATLLLSFLGMAWALQAADTCPEVKMVGLEGSDKLTILRGCPGLPGAPGDKGEAGTNGKRGERGPPGPPGKAGPPGPNGAPGEPQPCLTGPRTCKDLLDRGHFLSGWHTIYLPDCRPLTVLCDMDTDGGGWTVFQRRVDGSVDFYRDWATYKQGFGSRLGEFWLGNDNIHALTAQGTSELRVDLVDFEDNYQFAKLTFSLGKQVGNKFFLTNGEIMTFEKVKALCVKFQASVATPRNAAENGAIQNLIKEEAFLGITDEKTEGQFVDLTGNRLTYTNWNEGEPNNAGSDEDCVLLLKNGQWNDVPCSTSHLAVCEFPIFCN2MBLr3(SEQ ID NO120)
FCN2(信號(hào)序列+膠原蛋白到氨基酸92)MBL(始于氨基酸101卷曲螺旋+糖結(jié)合區(qū))MELDRAVGVLGAATLLLSFLGMAWALQAADTCPEVKMVGLEGSDKLTILRGCPGLPGAPGDKGEAGTNGKRGERGPPGPPGKAGPPGPNGAPPDGDSSLAASERKALQTEMARIKKWLTFSLGKQVGNKFFLTNGEIMTFEKVKALCVKFQASVATPRNAAENGAIQNLIKEEAFLGITDEKTEGQFVDLTGNRLTYTNWNEGEPNNAGSDEDCVLLLKNGQWNDVPCSTSHLAVCEFPIFCN2MBLr4(SEQ ID NO121)FCN2(信號(hào)序列+部分膠原蛋白到氨基酸93處的cons.K)MBL(始于氨基酸77處的cons.K其余的膠原蛋白+卷曲螺旋+糖結(jié)合區(qū))MELDRAVGVLGAATLLLSFLGMAWALQAADTCPEVKMVGLEGSDKLTILRGCPGLPGAPGDKGEAGTNGKRGERGPPGPPGKLGPPGNPGPSGSPGPKGQKGDPGKSPDGDSSLAASERKALQTEMARIKKWLTFSLGKQVGNKFFLTNGEIMTFEKVKALCVKFQASVATPRNAAENGAIQNLIKEEAFLGITDEKTEGQFVDLTGNRLTYTNWNEGEPNNAGSDEDCVLLLKNGQWNDVPCSTSHLAVCEFPIFCN2MBLr5(SEQ ID NO122)
FCN2(信號(hào)序列+部分膠原蛋白到氨基酸69處的cons.G)MBL(始于氨基酸64處的cons.G其余的膠原蛋白(包含“kick”)+卷曲螺旋+糖結(jié)合區(qū))MELDRAVGVLGAATLLLSFLGMAWALQAADTCPEVKMVGLEGSDKLTILRGCPGLPGAPGDKGEAGTNGQGLRGLQGPPGKLGPPGNPGPSGSPGPKGQKGDPGKSPDGDSSLAASERKALQTEMARIKKWLTFSLGKQVGNKFFLTNGEIMTFEKVKALCVKFQASVATPRNAAENGAIQNLIKEEAFLGIDEKTEGQFVDLTGNRLTYTNWNEGEPNNAGSDEDCVLLLKNGQWNDVPCSTSHLAVCEFPIFCN2MBLr6(SEQ ID NO123)MBL(取代的MBL膠原蛋白(氨基酸41到氨基酸99)+卷曲螺旋+糖結(jié)合區(qū))FCN2(插入的膠原蛋白氨基酸54到氨基酸92)MSLFPSLPLLLLSMVAASYSETVTCEDAQKTCPAVIACSSPGCPGLPGAPGDKGEAGTNGKRGERGPPGPPGKAGPPGPNGAPSPDGDSSLAASERKALQTEMARIKKWLTFSLGKQVGNKFFLTNGFIMTFEKVKALCVKFQASVATPRNAAENGAIQNLIKEEAFLGITDEKTEGQFVDLTGNRLTYTNWNEGEPNNAGSDEDCVLLLKNGQWNDVPCSTSHLAVCEFPIFCN2MBLr7(SEQ ID NO124)
MBL(信號(hào)序列到氨基酸25)FCN2(膠原蛋白到氨基酸93)MBL(始于氨基酸100卷曲螺旋+糖結(jié)合區(qū))MSLFPSLPLLLLSMVAASYSALQAADTCPEVKMVGLEGSDKLTILRGCPGLPGAPGDKGEAGTNGKRGERGPPGPPGKAGPPGPNGAPSPDGDSSLAASERKALQTEMARIKKWLTFSLGKQVGNKFFLTNGEIMTFEKVKALCVKFQASVATPRNAAENGAIQNLIKEEAFLGITDEKTEGQFVDLTGNRLTYTNWNEGEPNNAGSDEDCVLLLKNGQWNDVPCSTSHLAVCEFPI用于所有構(gòu)建的親代質(zhì)粒●pcDNA2003-cintMBLcDNA●Invitrogen Genestorm克隆RG000632(目錄號(hào)(Cat.No.)H-K 1000Invitrogen)。
用BD的BD In-FusionTMPCR克隆試劑盒(目錄號(hào)631774)通過(guò)重組進(jìn)行構(gòu)建。所述BD In-Fusion試劑盒可只基于載體和PCR產(chǎn)物末端之間2×15bp的同源性來(lái)克隆PCR產(chǎn)物。在用此試劑盒克隆時(shí)連接酶或磷酸酶是不必要的。所述In-Fusion酶捕捉DNA片段末端并將插入片段融合到所述載體。
用于PCR反應(yīng)的引物見(jiàn)表1所示PCR反應(yīng)和為重組進(jìn)行載體線性化質(zhì)?！癎enestorm RG000632”(批號(hào)N135-15C)在用Bstz17I消化后(N135-20B)進(jìn)行PCR反應(yīng)。用如下所述的引物對(duì)。PCR反應(yīng)的試劑盒是PfuUltraTMHotstart PCR Master Mix Stratagene#600630。在BioRAD i-循環(huán)儀(cycler)上用表2所示的溫度圖譜操作PCR反應(yīng)管。
為了進(jìn)行重組反應(yīng)，將載體pcDNA2001-cintMBLcDNA用如下所列的限制性酶消化來(lái)使其線性化。
FCN2MBLr1PCR所用引物Pr1-xho-MBLFCN+Pr4-Xmn-FCNMBL-rev(產(chǎn)物463bp)消化pcDNA2001-cintMBLcDNAXhoI+XmnI(部分)FCN2MBLr2PCR所用引物Pr1-xho-MBLFCN+Pr5-Xmn-FCNMBL-rev消化pcDNA2001-cintMBLcDNAXhoI+XmnI(部分)FCN2MBLr3PCR所用引物Pr1-xho-MBLFCN+Pr6-b-Bsp-FCNMBL-rev消化pcDNA2001-cintMBLcDNAXhoI+BspEIFCN2MBLr4PCR所用引物Pr1-xho-MBLFCN+Pr2-apa-FCNMBL-rev消化pcDNA2001-cintMBLcDNAXhoI+ApaIFCN2MBLr5PCR所用引物Pr1-xho-MBLFCN+Pr3-apa-FCNMBL-rev消化pcDNA2001-cintMBLcDNAXhoI+ApaIFCN2MBLr6PCR所用引物Pr8-BstAP-MBLFCN+Pr6-b-Bsp-FCNMBL-rev消化pcDNA2001-cintMBLcDNA部分BstAPI+BspEIFCN2MBLr7PCR所用引物Pr7-Alw-MBLFCN+Pr6-b-Bsp-FCNMBL-rev消化pcDNA2001-cintMBLcDNA部分AlwNI+BspEIIn-Fusion PCR重組反應(yīng)用約50-100ng的Quiagen Minelute純化的PCR產(chǎn)物和50-100ng的Quiagen Minelute純化的線性化pcDNA2001-cintMBLcDNA進(jìn)行In-FusionPCR重組反應(yīng)。
將1/10的重組反應(yīng)物轉(zhuǎn)化到MAX有效性的(efficiency)DH5α感受態(tài)細(xì)胞(Invitrogen目錄號(hào)18258-012)中。將每次轉(zhuǎn)化的1/10和9/10涂布在不同的含有200μg/ml氨芐青霉素的LB平板上。平板在37℃溫育過(guò)夜。
篩選陽(yáng)性克隆從每個(gè)試驗(yàn)平板上選出至少6個(gè)集落來(lái)進(jìn)行微量制備(miniprep)質(zhì)粒DNA的分離。為確定插入片段的存在，用酶PstI限制性消化分析DNA。選擇來(lái)自每個(gè)反應(yīng)的三個(gè)陽(yáng)性克隆來(lái)作進(jìn)一步研究。
限制性分析為確認(rèn)首次篩選后的所選重組質(zhì)粒個(gè)體，我們對(duì)所分離的質(zhì)粒DNA進(jìn)行深入的(intensive)限制性酶消化分析。
用表3所示的酶消化所述重組體的質(zhì)粒DNA。期望的片段也列在表中。所測(cè)試的所有重組克隆表現(xiàn)出預(yù)期的類型。EcoRI消化并非象預(yù)期的那樣。在重組體和親代質(zhì)粒的消化中都見(jiàn)到一個(gè)額外的片段。此偏差可被解釋為親代質(zhì)粒上多出了一個(gè)EcoR1位點(diǎn)。
結(jié)果所得到的重組質(zhì)粒見(jiàn)圖4-8的構(gòu)建體r1，-r2，-r3，-r4，和-r5。
實(shí)施例2瞬時(shí)表達(dá)人MBL和人FCN2的重組融合蛋白的試驗(yàn)2.1概述我們報(bào)道了重組人融合蛋白FCNMBLr1，F(xiàn)CNMBLr4，F(xiàn)CNMBLr5和MBL在HEK293和Per.C6細(xì)胞中的表達(dá)。我們發(fā)現(xiàn)瞬時(shí)轉(zhuǎn)染試驗(yàn)的細(xì)胞系至少能夠產(chǎn)生以活性寡聚體形式組裝的融合蛋白FCNMBLr4和FCNMBLr5，其結(jié)構(gòu)基本上類似MBL寡聚體形式3和4。融合蛋白FCNMBLr4和FCNMBLr5在結(jié)合糖表面和激活補(bǔ)體級(jí)聯(lián)反應(yīng)方面的表現(xiàn)與MBL一樣。
2.2介紹這些研究的目的是為了闡明制造由包含人ficolin2的膠原蛋白部分和人甘露糖結(jié)合型凝集素(MBL)組成的雜合蛋白的可能性。我們還希望明確是否此類分子仍具有結(jié)合到復(fù)合糖結(jié)構(gòu)的能力并仍能夠激活補(bǔ)體。
用兩株人源的HEK293和Per.C6真核細(xì)胞系作為宿主細(xì)胞株來(lái)被各自的表達(dá)質(zhì)粒瞬時(shí)轉(zhuǎn)染。由CMV-IE啟動(dòng)子增強(qiáng)子驅(qū)動(dòng)轉(zhuǎn)錄。
2.3試驗(yàn)材料和方法用于轉(zhuǎn)染試驗(yàn)的質(zhì)粒pME607-FCNMBL-r1，-r2，-r3，-r4，-r5，-r6和-r7(實(shí)施例1所述)所用細(xì)胞來(lái)源PerC6細(xì)胞從Crucell獲得。
HEK 293 Freestyle細(xì)胞從InVitrogen獲得。
培養(yǎng)基PerC6細(xì)胞在37℃，10％(vol/vol)CO2中維持無(wú)血清培養(yǎng)基中的單層。
HEK 293 Freestyle在37℃，8％(vol/vol)CO2中維持InVitrogen Freestyle培養(yǎng)基中的懸液形式。
轉(zhuǎn)染并收獲培養(yǎng)基用轉(zhuǎn)染試劑Lipofectamine以DNA轉(zhuǎn)染包含血清的培養(yǎng)基中的Per.C6細(xì)胞。轉(zhuǎn)染一天后將所述培養(yǎng)基置換為無(wú)血清培養(yǎng)基。
用轉(zhuǎn)染試劑293fect以DNA轉(zhuǎn)染無(wú)血清Freestyle培養(yǎng)基中的HEK293細(xì)胞。轉(zhuǎn)染后溫育約4天后收集所述培養(yǎng)基。
MBL定量重組MBL試驗(yàn)(TRIFMA)使用甘露聚糖包被的平板或mAb-131-01包被的平板。為了定量MBL，進(jìn)行時(shí)間分辨的免疫熒光測(cè)定法(time-resolvedimmunofluorometry)。
SDS-PAGE和Western印跡分析進(jìn)行SDS-PAGE之后，將蛋白電轉(zhuǎn)移到聚偏二氟乙烯(polyvinylidenediflouride)膜，并用單克隆抗-MBL抗體檢測(cè)MBL。
C4試驗(yàn)該試驗(yàn)被設(shè)計(jì)用來(lái)測(cè)量MBL和rMBL啟動(dòng)補(bǔ)體系統(tǒng)MBL凝集素-途徑的能力。與MBL相關(guān)的MBL相關(guān)性絲氨酸蛋白酶(MASP 2)裂解補(bǔ)體因子C4釋放C4a和C4b。C4b在甘露聚糖包被的ELISA平板上沉積(disposition)，它可用生物素標(biāo)記的抗C4b抗體和銪(Europium)標(biāo)記的鏈霉抗生物素蛋白(Streptavidin)檢測(cè)。
2.4結(jié)果在上述實(shí)驗(yàn)中，我們能夠在無(wú)血清條件下在HEK293和Per.C6細(xì)胞中瞬時(shí)表達(dá)FCN2MBLr4，F(xiàn)CN2MBLr5和MBL。
寡聚體形式的融合蛋白用非-還原變性SDS PAGE然后是western印跡來(lái)檢測(cè)寡聚體形式的融合蛋白。所述檢測(cè)抗體識(shí)別MBL的CDR部分(可能還有卷曲螺旋區(qū)的一部分)。結(jié)果見(jiàn)圖10所示。從該圖明顯可見(jiàn)，融合蛋白FCN2MBLr4和FCN2MBLr5最主要的形式是約250kDa，其對(duì)應(yīng)于由三條蛋白單鏈(24kDa)組成的亞基的3體或4體形式。寡聚形式的出現(xiàn)不依賴于所用的宿主細(xì)胞。MBL產(chǎn)生了很多的寡聚體形式。
結(jié)合性質(zhì)通過(guò)與甘露聚糖表面的結(jié)合并用識(shí)別MBL的CDR部分(可能還有卷曲螺旋區(qū)的一部分)的抗體進(jìn)行檢測(cè)，來(lái)測(cè)試融合蛋白的MBL糖結(jié)合區(qū)的功能。結(jié)果見(jiàn)表4所示?？梢缘贸鼋Y(jié)論FCN2MBLr4和FCN2MBLr5完全與MBL一樣在宿主細(xì)胞中表達(dá)，并且所述融合蛋白結(jié)合甘露聚糖表面。
MASP-2結(jié)合和C4裂解進(jìn)一步檢測(cè)所述融合蛋白結(jié)合MASP-2和激活MASP-2的絲氨酸蛋白酶的能力。這可以通過(guò)測(cè)量所述融合蛋白與甘露聚糖表面結(jié)合導(dǎo)致的MASP-2底物補(bǔ)體因子C4的裂解來(lái)進(jìn)行。結(jié)果見(jiàn)表5所示。從這些結(jié)果可以得出結(jié)論融合蛋白FCN2MBLr4和FCN2MBLr5保留了結(jié)合并激活MASP-2的能力。
討論上述結(jié)果清除闡明可以構(gòu)建FCN 2和MBL的融合蛋白，其具有如下性質(zhì)1.所述融合蛋白的寡聚體結(jié)構(gòu)比MBL蛋白的結(jié)構(gòu)更簡(jiǎn)單。
2.所述融合蛋白保持MBL通過(guò)與致密糖結(jié)構(gòu)結(jié)合而激活補(bǔ)體級(jí)聯(lián)反應(yīng)的基本性質(zhì)。
表1用于PCR反應(yīng)的引物黑體序列顯示在載體中重組所需的15bp同源性
表2

表3

表4 TRIFMA所測(cè)的MBL與甘露聚糖的結(jié)合

表5 融合蛋白的C4活性

權(quán)利要求
1.融合蛋白，其包含a)源自凝集素-補(bǔ)體途徑激活蛋白或其功能同系物的第一多肽序列；和b)源自膠原凝集素或其功能同系物的第二多肽序列；其中所述補(bǔ)體激活蛋白不是膠原凝集素。
2.根據(jù)權(quán)利要求1的融合蛋白，其中所述第一多肽序列能夠激活所述凝集素-補(bǔ)體途徑。
3.根據(jù)權(quán)利要求1的融合蛋白，其中所述第一多肽序列能連接至少一個(gè)MASP蛋白。
4.根據(jù)權(quán)利要求1的融合蛋白，其中所述第一多肽序列能連接選自由MASP-1，MASP-2和MASP-3組成的組的MASP蛋白或其功能同系物或變體。
5.根據(jù)權(quán)利要求1的融合蛋白，其中所述補(bǔ)體激活蛋白是ficolin。
6.根據(jù)權(quán)利要求5的融合蛋白，其中所述ficolin選自由L-ficolin，H-ficolin和M-ficolin組成的組。
7.根據(jù)權(quán)利要求5的融合蛋白，其中所述ficolin是L-ficolin。
8.根據(jù)權(quán)利要求1-7任一的融合蛋白，其中所述第一多肽序列包含補(bǔ)體激活蛋白的至少10個(gè)，如至少12個(gè)，例如至少15個(gè)，如至少20個(gè)，例如至少25個(gè)，如至少30個(gè)，例如至少35個(gè)，如至少40個(gè)，例如至少50個(gè)連續(xù)的氨基酸，或與其至少70％，如80％，例如90％，如95％相同的序列。
9.根據(jù)權(quán)利要求1的融合蛋白，其中所述第一多肽序列包含ficolin的膠原蛋白樣區(qū)或其功能同系物或變體。
10.根據(jù)權(quán)利要求1的融合蛋白，其中所述第一多肽序列包含L-ficolin的膠原蛋白樣區(qū)。
11.根據(jù)權(quán)利要求1的融合蛋白，其中所述第一多肽序列包含ficolin的半胱氨酸富集區(qū)或其功能同系物。
12.根據(jù)權(quán)利要求1的融合蛋白，其中所述第一多肽序列包含L-ficolin的半胱氨酸富集區(qū)。
13.根據(jù)權(quán)利要求1的融合蛋白，其中所述第一多肽序列包含ficolin的半胱氨酸富集區(qū)和膠原蛋白樣區(qū)或其功能同系物或變體。
14.根據(jù)權(quán)利要求1的融合蛋白，其中所述第一多肽序列包含L-ficolin的半胱氨酸富集區(qū)和膠原蛋白樣區(qū)。
15.根據(jù)權(quán)利要求1的融合蛋白，其中所述第一多肽序列包含SEQ ID.NO 1的氨基酸1-77。
16.根據(jù)權(quán)利要求1的融合蛋白，其中所述第二多肽序列能連接一個(gè)或更多個(gè)糖。
17.根據(jù)權(quán)利要求1的融合蛋白，其中所述膠原凝集素選自如下MBL(結(jié)合甘露糖的凝集素)，SP-A(肺表面活性蛋白A)，SP-D(肺表面活性蛋白D)，BK(或BC，牛共凝集素)和CL-43(膠原凝集素-43)。
18.根據(jù)權(quán)利要求17的融合蛋白，其中所述膠原凝集素是MBL。
19.根據(jù)權(quán)利要求1-18任一的融合蛋白，其中所述第二多肽序列包含膠原凝集素的至少10個(gè)，如至少12個(gè)，例如至少15個(gè)，如至少20個(gè)，例如至少25個(gè)，如至少30個(gè)，例如至少35個(gè)，如至少40個(gè)，例如至少50個(gè)連續(xù)的氨基酸，或與其至少70％，如80％，例如90％，如95％相同的序列。
20.根據(jù)權(quán)利要求1的融合蛋白，其中所述第二多肽序列包含膠原凝集素的CRD區(qū)或其功能同系物或變體。
21.根據(jù)權(quán)利要求1的融合蛋白，其中所述第二多肽序列包含MBL的CRD區(qū)。
22.根據(jù)權(quán)利要求1的融合蛋白，其中所述第二多肽序列包含MBL的頸區(qū)。
23.根據(jù)權(quán)利要求1的融合蛋白，其中所述第二多肽序列包含MBL的膠原蛋白樣區(qū)。
24.根據(jù)權(quán)利要求1的融合蛋白，其中所述第二多肽序列包含MBL的頸區(qū)和CRD區(qū)。
25.根據(jù)權(quán)利要求1的融合蛋白，其中所述第二多肽序列包含MBL的膠原蛋白樣區(qū)，頸區(qū)和CRD區(qū)。
26.根據(jù)權(quán)利要求1的融合蛋白，其中所述第二多肽序列包含SEQ ID.NO 2的氨基酸80-228。
27.根據(jù)權(quán)利要求1的融合蛋白，其中所述融合蛋白包含L-ficolin的半胱氨酸富集區(qū)和膠原蛋白樣區(qū)以及MBL的CRD區(qū)。
28.根據(jù)權(quán)利要求1的融合蛋白，其中所述融合蛋白包含L-ficolin的半胱氨酸富集區(qū)以及MBL的膠原蛋白樣區(qū)，頸區(qū)和CRD區(qū)。
29.根據(jù)權(quán)利要求1的融合蛋白，其中所述融合蛋白包含SEQ ID.NO.3所限的氨基酸序列，或其功能同系物。
30.根據(jù)權(quán)利要求1的融合蛋白，其中所述融合蛋白由SEQ ID.NO.3所限的氨基酸序列組成。
31.分離的核酸，其包含編碼根據(jù)權(quán)利要求1-30任一的融合蛋白的核苷酸序列。
32.包含權(quán)利要求31的核酸序列的載體。
33.包含權(quán)利要求32的載體的細(xì)胞。
34.根據(jù)權(quán)利要求33的細(xì)胞，其中所述細(xì)胞是哺乳動(dòng)物細(xì)胞。
35.根據(jù)權(quán)利要求33的細(xì)胞，其中所述細(xì)胞是非哺乳動(dòng)物細(xì)胞。
36.根據(jù)權(quán)利要求1-30任一的融合蛋白，其用作藥物。
37.在有需要的個(gè)體治療臨床狀況的方法，其包括給藥所述個(gè)體根據(jù)權(quán)利要求1-30任一的融合蛋白。
38.根據(jù)權(quán)利要求37的方法，其中所述臨床狀況是感染。
39.根據(jù)權(quán)利要求37的方法，其中所述個(gè)體是人。
40根據(jù)權(quán)利要求37的方法，其中所述個(gè)體是感染風(fēng)險(xiǎn)增加的人。
41.根據(jù)權(quán)利要求37的方法，其中所述個(gè)體是MBL血清水平低于正常的人。
42.根據(jù)權(quán)利要求37的方法，其中所述個(gè)體是MBL血清水平正常的人。
43.根據(jù)權(quán)利要求1-30任一的融合蛋白在制備用于治療有需要的個(gè)體的臨床狀況的藥物的用途。
44.根據(jù)權(quán)利要求43的用途，其中所述臨床狀況是感染。
45.根據(jù)權(quán)利要求43的用途，其中所述個(gè)體是人。
46.根據(jù)權(quán)利要求43的用途，其中所述個(gè)體是感染風(fēng)險(xiǎn)增加的人。
47.根據(jù)權(quán)利要求43的用途，其中所述個(gè)體是MBL血清水平低于正常的人。
48.根據(jù)權(quán)利要求43的用途，其中所述個(gè)體是MBL血清水平正常的人。
49.用于治療或預(yù)防有需要的個(gè)體的臨床狀況的藥物，其包含根據(jù)權(quán)利要求1-30任一的融合蛋白。
50.根據(jù)權(quán)利要求49的藥物，其中所述臨床狀況是感染。
51.根據(jù)權(quán)利要求49的藥物，其中所述個(gè)體是人。
全文摘要
本發(fā)明涉及能夠激活補(bǔ)體系統(tǒng)的融合蛋白，所述融合蛋白包含源自凝集素－補(bǔ)體途徑激活蛋白或其功能同系物的第一多肽序列；和源自膠原凝集素或其功能同系物的第二多肽序列；其中所述補(bǔ)體激活蛋白不是膠原凝集素。優(yōu)選的融合蛋白包含圖1的L－ficolin序列的氨基酸和圖2所示MBL序列的氨基酸。所述融合蛋白適用于治療中，包括產(chǎn)生，重建，增強(qiáng)和/或刺激所述補(bǔ)體系統(tǒng)的調(diào)理和/或殺細(xì)菌活性，即增強(qiáng)免疫防御識(shí)別并殺死微生物病原體的能力。因此，本發(fā)明涉及包含所述融合蛋白的藥物，生產(chǎn)所述融合蛋白的方法，和治療疾病，特別是感染的方法。
文檔編號(hào)A61P31/00GK1694961SQ03825026
公開(kāi)日2005年11月9日 申請(qǐng)日期2003年9月10日 優(yōu)先權(quán)日2002年9月10日
發(fā)明者利夫·康格斯萊夫, 迪特馬·韋爾吉尼, 芬恩·馬西森 申請(qǐng)人:內(nèi)蒂穆恩公司