Cloning of the human phenol sulfotransferase gene family: three genes implicated in the metabolism of catecholamines, thyroid hormones and drugs.

Phenol sulfotransferases (PST) catalyze the sulfonation of catecholamines, thyroid hormones and phenolic drugs. At least two major forms of human PST enzyme have been characterized biochemically from liver, platelets and other tissues, the phenol-preferring PST (P-PST) and the monoamine neurotransmitter-preferring PST (M-PST). Molecular cloning efforts worldwide over the past 7 years have resulted in the identification of numerous PST cDNA isolates representing alleles of three human PST 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), using somatic cell hybrids and cosmid clones. The two most closely related genes, STP1 and STP2, encoding P-PST isozymes have been mapped to a single cosmid clone and are, therefore, in close proximity to one another. STP1 and STP2 are approximately 96% identical at the amino acid sequence level, whereas, the STM gene (encoding M-PST) exhibits a lower level of identity (approximately 93-90.5%) relative to STP1 and STP2. STM is located at a distance of ca. 100 Kb from the STP1 and STP2 doublet. One may speculate that the three genes arose by gene duplication and/or gene conversion in humans. 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 of STP1 and STM from various tissues has revealed significant heterogeneity in the 5' nontranslated region, likely due to alternative splicing and/or tissue-specific promoter utilization. DNA polymorphisms have been detected in these genes in the human population and may be useful for molecular genetic studies of the metabolism of endogenous and xenobiotic phenolic molecules. Recent advances in the molecular biology of the human PST gene family are summarized.