HUMAN HYDROXYSTEROID SULFOTRANSFERASE SULT2B1 - 2 ENZYMES ENCODED BY A SINGLE CHROMOSOME-19 GENE

We have cloned and characterized cDNAs that encode two human hydroxyst eroid sulfotransferase (SULT) enzymes, SULT2B1a and SULT2B1b, as well as the single gene that encodes both of these enzymes. The two cDNAs d iffered at their 5'-termini and had 1050- and 1095-bp open reading fra mes that encoded 350 and 365 amino acids, respectively. The amino acid sequences encoded by these cDNAs included ''signature sequences'' tha t are conserved in all known cytosolic SULTs. Both cDNAs appeared, on the basis of amino acid sequence analysis, to be members of the hydrox ysteroid SULT ''family,'' SULT2, but they were only 48% identical in a mino acid sequence with the single known member of that family in huma ns, SULT2A1 (also referred to as DHEA ST). Northern blot analysis demo nstrated the presence of SULT2B1 mRNA species approximately 1.4 kb in length in human placenta, prostate, and trachea and-faintly-in small i ntestine 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 o r 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 S ULT gene SULT2A1 (previously STD). The divergence in 5'-terminal seque nces of the two SULT2B1 cDNAs resulted from alternative transcription initiation prior to different 5' exons, combined with alternative spli cing. SULT2B1 mapped to human chromosome band 19q13.3, approximately 5 00 kb telomeric to the location of SULT2A1. (C) 1998 Academic Press.