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软骨素-4-O-磺基转移酶-3的分子克隆与特性分析。磺基转移酶HNK-1家族的一个新成员。

Molecular cloning and characterization of chondroitin-4-O-sulfotransferase-3. A novel member of the HNK-1 family of sulfotransferases.

作者信息

Kang Hyung-Gyoo, Evers Matthias R, Xia Guoqing, Baenziger Jacques U, Schachner Melitta

机构信息

Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110 and Zentrum fuer Molekulare Neurobiologie, Universitaet Hamburg, Martinistrasse 52, D-20246 Hamburg, Germany.

出版信息

J Biol Chem. 2002 Sep 20;277(38):34766-72. doi: 10.1074/jbc.M204907200. Epub 2002 Jun 21.

DOI:10.1074/jbc.M204907200
PMID:12080076
Abstract

We have identified and characterized an N-acetylgalactosamine-4-O-sulfotransferase designated chondroitin-4-sulfotransferase-3 (C4ST-3) (GenBank accession number AY120869) based on its homology to HNK-1 sulfotransferase (HNK-1 ST). The cDNA predicts an open reading frame encoding a type II membrane protein of 341 amino acids with a 12-amino acid cytoplasmic domain and a 311-amino acid luminal domain containing a single potential N-linked glycosylation site. C4ST-3 has the greatest amino acid sequence identity when aligned with chondroitin-4-O-sulfotransferase 1 (C4ST-1) (45%) but also shows significant amino acid identity with chondroitin-4-O-sulfotransferase 2 (C4ST-2) (27%), dermatan-4-O-sulfotransferase 1 (29%), HNK-1 ST (26%), N-acetylgalactosamine-4-O-sulfotransferase 1 (26%), and N-acetylgalactosamine-4-O-sulfotransferase 2 (23%). C4ST-3 transfers sulfate to the C-4 hydroxyl of beta1,4-linked GalNAc that is substituted with a beta-linked glucuronic acid at the C-3 hydroxyl. The open reading frame of C4ST-3 is encoded by three exons located on human chromosome 3q21.3. Northern blot analysis reveals a single 2.1-kilobase transcript. C4ST-3 message is expressed in adult liver and at lower levels in adult kidney, lymph nodes, and fetal liver. Although C4ST-3 and C4ST-1 have similar specificities, the highly restricted pattern of expression seen for C4ST-3 suggests that it has a different role than C4ST-1.

摘要

基于其与HNK-1硫酸转移酶(HNK-1 ST)的同源性,我们鉴定并表征了一种名为软骨素-4-硫酸转移酶-3(C4ST-3)的N-乙酰半乳糖胺-4-O-硫酸转移酶(GenBank登录号AY120869)。该cDNA预测一个开放阅读框,编码一个341个氨基酸的II型膜蛋白,其具有一个12个氨基酸的胞质结构域和一个311个氨基酸的管腔结构域,该管腔结构域包含一个潜在的N-连接糖基化位点。与软骨素-4-O-硫酸转移酶1(C4ST-1)比对时,C4ST-3具有最高的氨基酸序列同一性(45%),但与软骨素-4-O-硫酸转移酶2(C4ST-2)(27%)、硫酸皮肤素-4-O-硫酸转移酶1(29%)、HNK-1 ST(26%)、N-乙酰半乳糖胺-4-O-硫酸转移酶1(26%)和N-乙酰半乳糖胺-4-O-硫酸转移酶2(23%)也显示出显著的氨基酸同一性。C4ST-3将硫酸基团转移至β1,4-连接的GalNAc的C-4羟基上,该GalNAc在C-3羟基处被β-连接的葡萄糖醛酸取代。C4ST-3的开放阅读框由位于人类染色体3q21.3上的三个外显子编码。Northern印迹分析显示有一个2.1千碱基的单一转录本。C4ST-3的信息在成体肝脏中表达,在成体肾脏、淋巴结和胎儿肝脏中表达水平较低。尽管C4ST-3和C4ST-1具有相似的特异性,但C4ST-3所呈现的高度受限的表达模式表明它具有与C4ST-1不同的作用。

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