The protein and the gene encoding the receptor for the cellular uptake of transcobalamin-bound cobalamin
The protein and the gene encoding the receptor for the cellular uptake of transcobalamin-bound cobalamin
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DOI：
10.1182/blood-2008-05-158949
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发表时间：
2009-01-01
期刊：
影响因子：
20.3
通讯作者：
Sequeira, Jeffrey M.
中科院分区：
文献类型：
--
作者：
Quadros, Edward V.;Nakayama, Yasumi;Sequeira, Jeffrey M.
细胞膜上的转钴胺(TC，TCII)受体(TCblR)与TC-钴胺(Cb1)结合，并通过内吞作用将复合体内化。用亲和层析法从人胎盘膜中纯化了该受体。从十二烷基硫酸钠-聚丙烯酰胺凝胶电泳胶中提取的蛋白质经胰酶消化后，经液相色谱/质谱分析，鉴定出4个与数据库中的一个膜蛋白匹配的多肽。TCblR属于低密度脂蛋白受体家族，由两个A型低密度脂蛋白受体结构域组成，中间有一个类似补体的半胱氨酸富集区。282个氨基酸序列包括31个残基的信号肽、198个残基的胞外区、21个残基的跨膜区和32个残基的胞内区。TC-Cbl的结合不需要胞内结构域或其在质膜上的定位，因为重组的胞外区与TC-Cbl结合具有高亲和力和特异性。该蛋白高度糖基化，经十二烷基硫酸钠-聚丙烯酰胺凝胶电泳法测得其大小为58 kDa。人类TCblR基因位于19号染色体短臂上的p13.2处，全长6.224 kb，由5个外显子和4个内含子组成。(血。2009；113：186-192)
The transcobalamin (TC, TCII) receptor (TCblR) on the plasma membrane binds TC-cobalamin (Cbl) and internalizes the complex by endocytosis. This receptor was purified from human placental membranes by affinity chromatography. Tryptic digest of the protein extracted from a sodium dodecyl sulfate-polyacrylamide gel electrophoresis gel and subjected to liquid chromatography/mass spectrometry identified 4 peptides that matched with a membrane protein in the data bank. TCblR belongs to the low-density lipoprotein receptor family, with 2 low-density lipoprotein receptor type A domains separated by a complement-like cysteine-rich region. The 282-amino acid sequence includes a signal peptide of 31 residues, extracellular domain of 198 residues, a transmembrane region of 21 residues, and a cytoplasmic domain of 32 residues. The binding of TC-Cbl does not require the cytoplasmic domain or its orientation in the plasma membrane because the recombinant extracellular domain binds TC-Cbl with high affinity and specificity. The protein is heavily glycosylated and accounts for the 58-kDa size by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The human gene first identified as 8D6A and more recently as CD 320 encoding TCblR is located at p13.2 on the short arm of chromosome 19, spans a length of 6.224 kb, and is composed of 5 exons and 4 introns. (Blood. 2009; 113: 186-192)