Human hydroxysteroid sulfotransferase SULT2B1: Two enzymes encoded by a single chromosome 19 gene
Human hydroxysteroid sulfotransferase SULT2B1: Two enzymes encoded by a single chromosome 19 gene
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DOI：
10.1006/geno.1998.5518
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发表时间：
1998-11-01
期刊：
影响因子：
4.4
通讯作者：
Weinshilboum, RM
中科院分区：
文献类型：
--
作者：
Her, C;Wood, TC;Weinshilboum, RM
我们已经克隆并鉴定了编码两种人羟基类固醇磺基转移酶（SULT），即SULT2B1a和SULT2B1b的cDNA，以及编码这两种酶的单个基因。这两种cDNA在其5'末端不同，分别具有1050和1095个碱基对的开放阅读框，分别编码350和365个氨基酸。这些cDNA编码的氨基酸序列包含在所有已知的胞质SULT中保守的“特征序列”。根据氨基酸序列分析，这两种cDNA似乎都是羟基类固醇SULT“家族”SULT2的成员，但它们与人类中该家族的唯一已知成员SULT2A1（也称为DHEA ST）的氨基酸序列仅有48%的同一性。Northern杂交分析表明，在人胎盘、前列腺和气管中存在长度约为1.4 kb的SULT2B1 mRNA种类，在小肠和肺中也有微弱表达。在COS - 1细胞中表达这两种人SULT2B1 cDNA表明，两种编码的蛋白质都能催化原型羟基类固醇SULT底物脱氢表雄酮的硫酸化，但都不能催化对硝基苯酚或17β - 雌二醇的硫酸结合，对硝基苯酚和17β - 雌二醇分别是苯酚和雌激素SULT亚家族的原型底物。这两种cDNA均由单个基因SULT2B1编码。SULT2B1中大多数外显子 - 内含子剪接位点的位置与唯一其他已知的人羟基类固醇SULT基因SULT2A1（先前为STD）相同。两种SULT2B1 cDNA在5'末端序列的差异是由于在不同的5'外显子之前的选择性转录起始，以及选择性剪接造成的。SULT2B1定位于人类染色体19q13.3带，距离SULT2A1的位置大约500 kb的端粒处。（C）1998学术出版社。
We have cloned and characterized cDNAs that encode two human hydroxysteroid sulfotransferase (SULT) enzymes, SULT2B1a and SULT2B1b, as well as the single gene that encodes both of these enzymes. The two cDNAs differed at their 5'-termini and had 1050- and 1095-bp open reading frames that encoded 350 and 365 amino acids, respectively. The amino acid sequences encoded by these cDNAs included "signature sequences" that are conserved in all known cytosolic SULTs. Both cDNAs appeared, on the basis of amino acid sequence analysis, to be members of the hydroxysteroid SULT "family," SULT2, but they were only 48% identical in amino acid sequence with the single known member of that family in humans, SULT2A1 (also referred to as DHEA ST). Northern blot analysis demonstrated the presence of SULT2B1 mRNA species approximately 1.4 kb in length in human placenta, prostate, and trachea and-faintly-in small intestine and lung. Expression of the two human SULT2B1 cDNAs in COS-l cells showed that both of the encoded proteins catalyzed sulfation of the prototypic hydroxysteroid SULT substrate, dehydroepiandrosterone, but both failed to catalyze the sulfate conjugation of 4-nitrophenol or 17 beta-estradiol, prototypic substrates for the phenol and estrogen SULT subfamilies. Both of these cDNAs were encoded by a single gene, SULT2B1. The locations of most exonintron splice junctions in SULT2B1 were identical to those of the only other known human hydroxysteroid SULT gene SULT2A1 (previously STD). The divergence in 5'-terminal sequences of the two SULT2B1 cDNAs resulted from alternative transcription initiation prior to different 5' exons, combined with alternative splicing. SULT2B1 mapped to human chromosome band 19q13.3, approximately 500 kb telomeric to the location of SULT2A1. (C) 1998 Academic Press.