Molecular biology of the human phenol sulfotransferase gene family.
Cytosolic phenol sulfotransferases (PST) catalyze the sulfation/sulfonation of various phenolic agents, including catecholamines, thyroid hormones, and drugs (e.g., minoxidil and acetaminophen), which usually results in the inactivation and subsequent excretion of the compound. Our recent efforts have focused on the cloning and sequencing of the human gene family encoding the PST isozymes, and the results are summarized in this article. Multiple PST cDNA isolates have been cloned in various laboratories representing alleles of three phenol sulfotransferase gene loci termed as STP1, STP2, and STM. All three genes have been mapped precisely to a small region on human chromosome 16p12.1-p11.2 (homologous to mouse chromosome 7). The two most closely related genes, STP1 and STP2, encode isozymes of phenol-preferring PST (P-PST) and have been mapped to a single genomic cosmid clone, thus in proximity to one another. The STM gene encoding the monoamine neurotransmitter-preferring PST (M-PST) exhibits a lower level of similarity relative to STP1 and STP2. Genomic clones have been sequenced to determine the genomic organization for each of the three highly related genes. All contain seven coding exons, with conserved intron-exon boundaries. Sequencing of individual cDNA isolates from various tissues has revealed heterogeneity in the 5' nontranslated regions, likely due to tissue-specific promoter utilization (or perhaps alternative splicing). DNA and protein polymorphisms have been identified in the population and may be useful for molecular genetic studies of the variability in the metabolism of catecholamines, thyroid hormones, and phenolic drugs, and possibly neuropsychiatric or other metabolic disorders.
Dooley
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Department of Molecular Pharmacology, Southern Research Institute, Birmingham, Alabama 35205, USA. dooley@sri.org
D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000032:analysis; D005786:Gene Expression Regulation; D014644:Genetic Variation; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D005810:Multigene Family; D017421:Sequence Analysis; D015238:Sulfotransferases / Q000235:genetics*
D018076:DNA, Complementary; D007527:Isoenzymes; D015238:Sulfotransferases