Three genes that encode human beta-galactoside alpha 2,3-sialyltransferases. Structural analysis and chromosomal mapping studies.

Three genes that encode human beta-galactoside alpha 2,3-sialyltransferases. Structural analysis and chromosomal mapping studies.
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编码人类 β-半乳糖苷 α 2,3-唾液酸转移酶的三个基因。

DOI:
10.1093/glycob/5.3.319
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发表时间:
1995
期刊:
影响因子:
4.3
通讯作者:
Lau,JT
Lau,JT
中科院分区:
生物学3区
文献类型:
--
作者:
Chang,ML;Eddy,RL;Shows,TB;Lau,JT

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α 2,3-连接唾液酸合成Gal(β 1,3)GalNAc由至少三种β-半乳糖苷α 2,3-唾液酸转移酶(EC 2.4.99.4,SiaT-4)介导,这些酶由三种不同的基因编码。相比之下,只有一个基因编码β-半乳糖苷α 2,6-唾液酸转移酶(EC 2.4.99.1,SiaT-1)。本报告评估了SiaT-4基因的关系和性质。人-小鼠体细胞杂交分析表明,唾液酸转移酶基因分散在人类基因组中。SiaT-4a的基因位于8号染色体,SiaT-4 b的基因位于1号染色体的p21-p34,SiaT-4c的基因位于11号染色体的q23.3-qter。这些基因的基因符号分别被命名为SIAT 4A、SIAT 4 B和SIAT 4C。为了评估SiaT-4基因之一的结构组织,分离并表征了来自颌下腺的人SiaT-4a cDNA。cDNA 5′末端快速扩增(5′-RACE)分析显示一个异常长的1 kb 5-非翻译前导序列。克隆序列的催化结构域在转染细胞中表达,并显示其能够介导唾液酸α23特异性合成Gal(β 1,3)GalNAc-R。还分离并检查了SiaT-4a的基因组序列。这些数据表明,SiaT-4a蛋白的编码信息分散到七个离散的外显子片段的方式让人想起SiaT-1基因。此外,如在SiaT-1基因中,插入序列中断了所有已知唾液酸转移酶中保守的两个唾液酸基序结构域
The synthesis of α2,3-linked sialic acid to Gal(β1,3)GalNAc is mediated by at least three β-galactoside α2,3-sialyltransferases (EC 2.4.99.4, SiaT-4) that are encoded by three distinct genes. In contrast, only a single gene encodes the β-galactoside α2,6-sialyltransferase (EC 2.4.99.1, SiaT-1). This report assesses the relationship and nature of the SiaT-4 genes. Analysis of human-mouse somatic cell hybrids demonstrates that the sialyltransferase genes are dispersed in the human genome. The gene for SiaT-4a resides in chromosome 8, that for SiaT-4b resides in p21–p34 of chromosome 1 and that for SiaT-4c in q23.3-qter of chromosome 11. The gene symbols for these genes have been designated SIAT4A, SIAT4B and SIAT4C, respectively. To assess the structural organization of one of the SiaT-4 genes, a human SiaT-4a cDNA from submaxillary glands was isolated and characterized. Rapid amplification of cDNA 5′ ends (5′-RACE) analysis indicates an unusually long 1 kb 5-untranslated leader. The catalytic domain of the cloned sequence was expressed in transfected cells and was shown to be competent in mediating the specific synthesis of sialic acid α23 to Gal(β1,3)GalNAc-R. Genomic sequences for SiaT-4a were also isolated and examined. The data demonstrate that coding information for SiaT-4a protein is dispersed into seven discrete exon segments in a manner reminiscent of the SiaT-1 gene. Furthermore, as in the SiaT-1 gene, intervening sequences interrupt both sialylmotif domains, regions that are conserved among all known sialyltransferases