Human sulfotransferases SULT1C1 and SULT1C2: cDNA characterization, gene cloning, and chromosomal localization

Sulfate conjugation catalyzed by sulfotransferase (SULT) enzymes is an impo rtant pathway in the biotransformation of many drugs, other xenobiotics, ne urotransmitters, and hormones. We previously described a human cDNA, SULT1C 1, that encoded a protein similar in sequence to that of rat ST1C1. Subsequ ently, a related human cDNA, SULT1C2, was reported. In the present study, w e set out to characterize further the human SULT1C1 cDNA and then to clone, structurally characterize, and map its gene. As an initial step, we perfor med 5'- and 3'-RACE with SULT1C1 cDNA. Those experiments demonstrated that a small number of SULT1C1 transcripts contained an "insert," which we later showed resulted from alternative splicing that involved an Alu sequence in intron 3 of SULT1C1. We then cloned and structurally characterized the SUL T1C1 gene from a human genomic BAC library. Because the sequence of SULT1C2 was closely related to that of SULT1C1 and because the genes for other hum an SULT paralogues occur in clusters, we screened the BAC clones that had b een positive for SULT1C1 to search for SULT1C2 and discovered a clone that contained both genes. That BAC was used to sequence and structurally charac terize SULT1C2. SULT1C1 and SULT1C2 were approximately 21 and 10 kb in leng th, respectively. Both genes contained seven exons that encoded protein, an d both had structures that were similar to those of other genes that encode members of the SULT1 family. Finally, human SULT1C1 and SULT1C2 mapped to 2q11.2 by fluorescence in situ hybridization. The cloning and structural ch aracterization of SULT1C1 and SULT1C2 will now make it possible to perform molecular genetic and pharmacogenomic studies of these sulfate-conjugating enzymes in humans, (C) 2000 Academic Press.