Molecular cloning and chromosomal localization of human membrane cofactor protein (MCP). Evidence for inclusion in the multigene family of complement-regulatory proteins.
Molecular cloning and chromosomal localization of human membrane cofactor protein (MCP). Evidence for inclusion in the multigene family of complement-regulatory proteins.
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DOI：
10.1084/jem.168.1.181
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发表时间：
1988-07-01
期刊：
影响因子：
--
通讯作者：
Atkinson JP
中科院分区：
文献类型：
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作者：
Lublin DM;Liszewski MK;Post TW;Arce MA;Le Beau MM;Rebentisch MB;Lemons LS;Seya T;Atkinson JP
膜辅助因子蛋白（MCP）是补体系统的一种调节分子，具有辅助因子活性，可介导因子i介导的C3b和C4b失活。MCP广泛分布于白细胞、血小板、内皮细胞、上皮细胞和成纤维细胞。MCP从人T细胞系HSB2中纯化得到，通过Edman降解得到nh2端24个氨基酸序列。利用基于该序列的寡核苷酸探针从人单核细胞（U937） cDNA文库中鉴定出一个克隆。核苷酸测序显示一个43-bp的5'-未翻译区，一个1152 bp的开放阅读框，一个335-bp的3'-未翻译区，后面是一个16 bp的poly(a) track。推导出的全长MCP蛋白由34个氨基酸的信号肽和350个氨基酸的成熟蛋白组成。该蛋白从NH2端开始，具有四个大约60个氨基酸的重复单元，与补体调节蛋白（c3b受体或CR1， c3d受体或CR2，衰变加速因子，c4结合蛋白和因子H）以及其他几种补体和非补体蛋白的多基因家族中的一致序列相匹配。MCP蛋白的其余部分包括25个富含丝氨酸和苏氨酸的氨基酸（可能是MCP重o链糖基化的位点），17个意义未知的氨基酸，以及一个23个氨基酸的跨膜疏水区，后面是一个33个氨基酸的细胞质尾部。通过人-鼠体细胞杂交克隆分析和原位杂交，将MCP基因定位于人1号染色体1q31-41带。这个相同的遗传区域包含互补调节蛋白的多基因家族，因此扩大到包括功能和结构相关的MCP。
Membrane cofactor protein (MCP), a regulatory molecular of the complement system with cofactor activity for the factor I-mediated inactivation of C3b and C4b, is widely distributed, being present on leukocytes, platelets, endothelial cells, epithelial cells, and fibroblasts. MCP was purified from a human T cell line (HSB2) and the NH2-terminal 24-amino acid sequence obtained by Edman degradation. An oligonucleotide probe based on this sequence was used to identify a clone from a human monocytic (U937) cDNA library. Nucleotide sequencing showed a 43-bp 5'-untranslated region, an open reading frame of 1,152 bp, and a 335-bp 3'-untranslated region followed by a 16-bp poly(A) track. The deduced full-length MCP protein consists of a 34-amino acid signal peptide and a 350-amino acid mature protein. The protein has, beginning at the NH2 terminus, four approximately 60-amino acid repeat units that match the consensus sequence found in a multigene family of complement regulatory proteins (C3b-receptor or CR1, C3d-receptor or CR2, decay-accelerating factor, C4-binding protein, and factor H), as well as several other complement and non-complement proteins. The remainder of the MCP protein consists of 25 amino acids that are rich in serine and threonine (probable site of heavy O-linked glycosylation of MCP), 17 amino acids of unknown significance, and a 23-amino acid transmembrane hydrophobic region followed by a 33-amino acid cytoplasmic tail. The MCP gene was localized to human chromosome 1, bands 1q31-41, by analysis of human x rodent somatic cell hybrid clones and by in situ hybridization. This same genetic region contains the multigene family of complement-regulatory proteins, which is thereby enlarged to include the functionally and structurally related MCP.