Human Sulfotransferases SULT1C1 and SULT1C2: cDNA Characterization, Gene Cloning, and Chromosomal Localization

Freimuth, Robert R.; Raftogianis, Rebecca B.; Wood, Thomas O.; Moon, Eunpyo; Kim, Ung Jin; Xu, Jun; Siciliano, Michael J.; Weinshilboum, Richard M.

doi:10.1006/geno.2000.6150

Cited by 41 publications

(40 citation statements)

References 42 publications

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“…The human SULT1C2 referred to here was called SULT1C1 or SULT1C sulfotransferase 1 in the original descriptions, 18,19,75 and the human SULT1C4 referred to here was originally called SULT1C2 or SULT1C sulfotransferase. 19,75 considering further: SULTs 1C2 and 1C4 appear to be most highly expressed in fetal tissues, 13 although RNA dot blots indicated the adult stomach and kidney (SULT1C2) and ovary (SULT1C4) may be sites of expression. 18,19 However the function of these enzymes in humans is not clear.…”

Section: The Sulfotransferase Superfamily-organisation and Functionmentioning

confidence: 99%

Sulfation through the looking glass—recent advances in sulfotransferase research for the curious

2002

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Members of the cytosolic sulfotransferase (SULT) superfamily catalyse the sulfation of a multitude of xenobiotics, hormones and neurotransmitters. Humans have at least 10 functional SULT genes, and a number of recent advances reviewed here have furthered our understanding of SULT function. Analysis of expression patterns has shown that sulfotransferases are highly expressed in the fetus, and SULTs may in fact be a major detoxification enzyme system in the developing human. The X-ray crystal structures of three SULTs have been solved and combined with mutagenesis experiments and molecular modelling, they have provided the first clues as to the factors that govern the unique substrate specificities of some of these enzymes. In the future these and other studies will facilitate prediction of the fate of chemicals metabolised by sulfation. Variation in sulfation capacity may be important in determining an individual's response to xenobiotics, and there has been an explosion in information on sulfotransferase polymorphisms and their functional consequences, including the influence of SULT1A1 genotype on susceptibility to colorectal and breast cancer. Finally, the first gene knockout experiments with SULTs have recently been described, with the generation of estrogen sulfotransferase deficient mice in which reproductive capacity is compromised. Our improved understanding of these enzymes will have significant benefits in such diverse areas as drug design and development, cancer susceptibility, reproduction and development.

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Section: The Sulfotransferase Superfamily-organisation and Functionmentioning

confidence: 99%

Sulfation through the looking glass—recent advances in sulfotransferase research for the curious

2002

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“…Molecules that belong to the sulfotransferase superfamily, on the basis of aminoacid sequence similarities and substrate preferences, can be divided into two major categories, SULT1 (phenol SULTs) and SULT2 (hydroxysteroid SULTs) Freimuth et al 2000). Members of the SULT1 subfamily share at least 60% identity in amino-acid sequence, but are further subdivided into four groups; namely, phenol (1A), thyroid hormone (1B), hydroxyarylamine (1C), and estrogen (1E) sulfotransferases.…”

Section: Introductionmentioning

confidence: 99%

Catalog of 320 single nucleotide polymorphisms (SNPs) in 20 quinone oxidoreductase and sulfotransferase genes

et al. 2001

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Single nucleotide polymorphisms (SNPs) in genes encoding drug-metabolizing enzymes, transporters, receptors, and other drug targets have been widely implicated as contributors to differences among individuals as regards the efficacy and toxicity of many medications, as well as the susceptibility to complex diseases. By combining the polymerase chain reaction (PCR) technique with direct sequencing, we screened genomic DNAs from 48 Japanese volunteers for SNPs in genes encoding three quinone oxidoreductases (NQO1, NQO2, and PIG3) and 17 sulfotransferases (SULT1A1, SULT1A2, SULT1A3, SULT1C1, SULT1C2, SULT2A1, SULT2B1, ST1B2, TPST1, TPST2, SULTX3, STE, CST, CHST2, CHST4, and CHST5). In all, we identified 320 SNPs from these 20 loci: 22 within coding elements, 21 in 5Ј flanking regions, 10 in 5Ј untranslated regions, 223 in introns, 19 in 3Ј untranslated regions, and 25 in 3Ј flanking regions. The ratio of transitions to transversions was approximately 2.3 to 1. Of the 22 coding SNPs, 6 were nonsynonymous substitutions that resulted in amino-acid substitutions. The highdensity SNP maps we constructed from this data for each of the quinone oxidoreductases and sulfotransferases examined here should provide useful information for investigations designed to detect association(s) between genetic variations and common diseases or responsiveness to drug therapy.

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“…The gene structures for SULT1C1 (approximately 20 kb long) and SULT1C2 (about 10 kb in length) have been reported previously. 21 Both the SULT1C1 and SULT1C2 genes contain seven exons that encode the protein ( Figure 1). However, the SULT1C1 gene contains an additional 5 0 -noncoding exon as well as a rarely expressed alternatively spliced exon located within intron 3.…”

Section: The Chromosome 2 Cluster and Sult6b1mentioning

confidence: 99%

“…SULT1B1 also contains seven protein-coding exons that span 28 kb (Figure 1), but since no RACE data were reported for this gene, no noncoding regions could be identified. 21 SULT1D1P shares homology with the conserved gene structures for other SULT1 family genes (Figure 2b), and is about 22 kb in length. A potential TATA box (TATTAA) is located 60 bp upstream of the putative translation initiation codon.…”

Section: The Chromosome 4 Clustermentioning

confidence: 99%

“…3,[10][11][12][13][14][15] While the cDNAs for some of those genes were cloned after purification and sequencing of the expressed protein, many were subsequently identified and cloned using homology-based techniques that took advantage of the highly conserved sequences in Regions I and IV. Eight of the human genes were characterized using PCR and DNA sequencing methods, 12,[16][17][18][19][20][21] but the genes for SULT1B1 and 4A1 were characterized by annotation of publicly available genomic sequence data generated by the Human Genome Project (unpublished observations 22 ). All 10 of these genes share very similar gene structures, both with regard to the number and length of coding exons as well as the locations of splice junctions within the translated amino-acid sequence ( Figure 1).…”

Section: Introductionmentioning

confidence: 99%

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Human cytosolic sulfotransferase database mining: identification of seven novel genes and pseudogenes

et al. 2003

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A total of 10 SULT genes are presently known to be expressed in human tissues. We performed a comprehensive genome-wide search for novel SULT genes using two different but complementary approaches, and developed a novel graphical display to aid in the annotation of the hits. Seven novel human SULT genes were identified, five of which were predicted to be pseudogenes, including two processed pseudogenes and three pseudogenes that contained introns. Those five pseudogenes represent the first unambiguous SULT pseudogenes described in any species. Expression-profiling studies were conducted for one novel gene, SULT6B1, and a series of alternatively spliced transcripts were identified in the human testis. SULT6B1 was also present in chimpanzee and gorilla, differing at only seven encoded amino-acid residues among the three species. The results of these database mining studies will aid in studies of the regulation of these SULT genes, provide insights into the evolution of this gene family in humans, and serve as a starting point for comparative genomic studies of SULT genes.

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Human Sulfotransferases SULT1C1 and SULT1C2: cDNA Characterization, Gene Cloning, and Chromosomal Localization

Cited by 41 publications

References 42 publications

Sulfation through the looking glass—recent advances in sulfotransferase research for the curious

Sulfation through the looking glass—recent advances in sulfotransferase research for the curious

Catalog of 320 single nucleotide polymorphisms (SNPs) in 20 quinone oxidoreductase and sulfotransferase genes

Human cytosolic sulfotransferase database mining: identification of seven novel genes and pseudogenes

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