Petersen C M, Nielsen M S, Nykjaer A, Jacobsen L, Tommerup N, Rasmussen H H, Roigaard H, Gliemann J, Madsen P, Moestrup S K
Department of Medical Biochemistry, University of Aarhus, 8000 Aarhus C, Denmark.
J Biol Chem. 1997 Feb 7;272(6):3599-605. doi: 10.1074/jbc.272.6.3599.
Receptor-associated protein (RAP) is an endoplasmic reticulum/Golgi protein involved in the processing of receptors of the low density lipoprotein receptor family. A approximately 95-kDa membrane glycoprotein, designated gp95/sortilin, was purified from human brain extracts by RAP affinity chromatography and cloned in a human cDNA library. The gene maps to chromosome 1p and encodes an 833-amino acid type I receptor containing an N-terminal furin cleavage site immediately preceding the N terminus determined in the purified protein. Gp95/sortilin is expressed in several tissues including brain, spinal cord, and testis. Gp95/sortilin is not related to the low density lipoprotein receptor family but shows intriguing homologies to established sorting receptors: a 140-amino acid lumenal segment of sortilin representing a hitherto unrecognized type of extracellular module shows extensive homology to corresponding segments in each of the two lumenal domains of yeast Vps10p, and the extreme C terminus of the cytoplasmic tail of sortilin contains the casein kinase phosphorylation consensus site and an adjacent dileucine sorting motif that mediate assembly protein-1 binding and lysosomal sorting of the mannose-6-phosphate receptors. Expression of a chimeric receptor containing the cytoplasmic tail of gp95/sortilin demonstrates evidence that the tail conveys colocalization with the cation-independent mannose6-phosphate receptor in endosomes and the Golgi compartment.
受体相关蛋白（RAP）是一种内质网/高尔基体蛋白，参与低密度脂蛋白受体家族受体的加工过程。一种约95 kDa的膜糖蛋白，命名为gp95/分拣蛋白，通过RAP亲和层析从人脑提取物中纯化，并在人cDNA文库中克隆。该基因定位于1号染色体，编码一个833个氨基酸的I型受体，在纯化蛋白中确定的N末端之前紧邻一个N末端弗林蛋白酶切割位点。Gp95/分拣蛋白在包括脑、脊髓和睾丸在内的多种组织中表达。Gp95/分拣蛋白与低密度脂蛋白受体家族无关，但与已确定的分拣受体显示出有趣的同源性：分拣蛋白的一个140个氨基酸的腔内片段代表一种迄今未被识别的细胞外模块类型，与酵母Vps10p的两个腔内结构域中每个结构域的相应片段具有广泛的同源性，并且分拣蛋白细胞质尾巴的极端C末端包含酪蛋白激酶磷酸化共有位点和一个相邻的双亮氨酸分拣基序，介导装配蛋白-1结合和甘露糖-6-磷酸受体的溶酶体分拣。含有gp95/分拣蛋白细胞质尾巴的嵌合受体的表达证明了该尾巴在内体和高尔基体区室中与不依赖阳离子的甘露糖6-磷酸受体共定位。
