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Gene Review

SULT1A1  -  sulfotransferase family, cytosolic, 1A,...

Homo sapiens

Synonyms: Aryl sulfotransferase 1, HAST1/HAST2, OK/SW-cl.88, P-PST, P-PST 1, ...
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Disease relevance of SULT1A1

  • SULT1A1 catalyzes 2-methoxyestradiol sulfonation in MCF-7 breast cancer cells [1].
  • MeAalphaC, tested in the presence of rat liver post-mitochondrial fraction, showed strongly enhanced mutagenicity in a Salmonella typhimurium strain expressing human SULT1A1 compared with the control (recipient) strain TA1538/1,8-DNP (deficient in endogenous acetyltransferase) [2].
  • We conclude that smoking increases risk of colorectal adenomas and that SULT1A1 and NAT2 only modestly modify this association [3].
  • METHODS: In this study, 306 Japanese patients with urothelial transitional cell carcinoma and 306 healthy controls were compared for frequencies of CYP1A2, SULT1A1, and NAT2 genotypes [4].
  • We thus hypothesized that the variant SULT1A1 allele may protect against the risk of lung cancer related to tobacco smoking [5].

Psychiatry related information on SULT1A1


High impact information on SULT1A1

  • There may be some interaction between the two alpha subtype-mediated effects in some nephron segments. beta-Adrenergic agonists stimulate cAMP formation in the PST, thick ascending limb (rat and mouse), CNT, and collecting duct segments [11].
  • Genetic polymorphisms are observed on such human sulfotransferases as ST1A2, ST1A3, and ST2A3 [12].
  • Patient survival was evaluated according to SULT1A1 genotype using Kaplan-Meier survival functions [13].
  • BACKGROUND: Human sulfotransferase 1A1 (SULT1A1) catalyzes the sulfation of a variety of phenolic and estrogenic compounds, including 4-hydroxytamoxifen (4-OH TAM), the active metabolite of tamoxifen [13].
  • Is ATP (adenosine 5'-triphosphate), like STP, a performance-enhancing additive for the tanks of cancer patients [14]?

Chemical compound and disease context of SULT1A1


Biological context of SULT1A1


Anatomical context of SULT1A1


Associations of SULT1A1 with chemical compounds

  • The presence of two p-nitrophenol (pNP) molecules in the crystal structure of SULT1A1 was postulated to explain cooperativity at low and inhibition at high substrate concentrations, respectively [19].
  • In SULT1A1, substrate inhibition occurs with pNP as the substrate but not with dopamine [19].
  • We have investigated the sulfation of the prohormone T4, the active hormone T3, and the metabolites rT3 and 3,3'-diiodothyronine (3,3'-T2) by human liver and kidney cytosol as well as by recombinant human SULT1A1 and SULT1A3, previously known as phenol-preferring and monoamine-preferring phenol sulfotransferase, respectively [20].
  • The apparent Km values of 3,3'-T2 and T3 [at 50 micromol/L 3'-phosphoadenosine-5'-phosphosulfate (PAPS)] were 1.02 and 54.9 micromol/L for liver cytosol, 0.64 and 27.8 micromol/L for kidney cytosol, 0.14 and 29.1 micromol/L for SULT1A1, and 33 and 112 micromol/L for SULT1A3, respectively [20].
  • Of the latter, SULT1A1 clearly shows the highest affinity for both iodothyronines and PAPS, but it remains to be established whether it is the prominent isoenzyme for sulfation of thyroid hormone in human liver and kidney [20].

Physical interactions of SULT1A1

  • PST and membrane-bound COMT were found to have the lowest Km values for both catecholamines [26].

Enzymatic interactions of SULT1A1


Regulatory relationships of SULT1A1

  • The ability of hM-PST to sulfate a number of xenobiotics was examined and compared with the bacterially expressed human phenol-sulfating form of PST (hP-PST) [28].
  • SULT1A1 mRNA abundance was 39% higher (p < 0.05) in dexamethasone-treated calves compared with control calves. mRNA abundance of CYP2C8 tended also to be higher (+44%; p = 0.053) after dexamethasone treatment [29].
  • The natural xanthones reversibly inhibited SULT1A1 with IC50 values ranging from 1.6 to 7 microM whereas much higher amounts of these compounds were required to inhibit SULT2A1 (IC50 values of 26-204 microM) [30].
  • Involvement of p38 MAPK and Nrf2 in phenolic acid-induced P-form phenol sulfotransferase expression in human hepatoma HepG2 cells [31].

Other interactions of SULT1A1

  • The change of a single amino acid, E146A, was sufficient to transform the catalytic properties and substrate preference of SULT1A3, such that they closely resembled those of SULT1A1 [32].
  • We set out to compare the frequencies of common SULT1A1 and SULT1A2 alleles in Caucasian, Chinese and African-American subjects [22].
  • Combinations of SULT1A1 fast sulfation (*1/*1) and of NAT2 slow acetylation with smoking resulted in a 4 times higher risk of adenomas compared to never smokers with other inherited gene variants, although there was no statistically significant effect modification [3].
  • Alternatively, the Val CYP1B1 or His SULT1A1 allele with modified ability to metabolize estrogens could increase the level of genotoxic catechol estrogen (i.e., 4-hydroxy-estradiol) among smokers [21].
  • Several other human SULTs (in particular 1A3 and 1C1) as well as human NAT2 (unlike NAT1) also activated nitrofen, but were markedly less efficient than SULT1A1 [33].

Analytical, diagnostic and therapeutic context of SULT1A1


  1. SULT1A1 catalyzes 2-methoxyestradiol sulfonation in MCF-7 breast cancer cells. Spink, B.C., Katz, B.H., Hussain, M.M., Pang, S., Connor, S.P., Aldous, K.M., Gierthy, J.F., Spink, D.C. Carcinogenesis (2000) [Pubmed]
  2. Bioactivation of the heterocyclic aromatic amine 2-amino-3-methyl-9H-pyrido [2,3-b]indole (MeAalphaC) in recombinant test systems expressing human xenobiotic-metabolizing enzymes. Glatt, H., Pabel, U., Meinl, W., Frederiksen, H., Frandsen, H., Muckel, E. Carcinogenesis (2004) [Pubmed]
  3. Effect of SULT1A1 and NAT2 genetic polymorphism on the association between cigarette smoking and colorectal adenomas. Tiemersma, E.W., Bunschoten, A., Kok, F.J., Glatt, H., de Boer, S.Y., Kampman, E. Int. J. Cancer (2004) [Pubmed]
  4. Cytochrome P450 (CYP) 1A2, sulfotransferase (SULT) 1A1, and N-acetyltransferase (NAT) 2 polymorphisms and susceptibility to urothelial cancer. Tsukino, H., Kuroda, Y., Nakao, H., Imai, H., Inatomi, H., Osada, Y., Katoh, T. J. Cancer Res. Clin. Oncol. (2004) [Pubmed]
  5. A functional polymorphism in the SULT1A1 gene (G638A) is associated with risk of lung cancer in relation to tobacco smoking. Liang, G., Miao, X., Zhou, Y., Tan, W., Lin, D. Carcinogenesis (2004) [Pubmed]
  6. SULT1A1 polymorphism and esophageal cancer in males. Wu, M.T., Wang, Y.T., Ho, C.K., Wu, D.C., Lee, Y.C., Hsu, H.K., Kao, E.L., Lee, J.M. Int. J. Cancer (2003) [Pubmed]
  7. Human phenol sulfotransferases SULT1A2 and SULT1A1: genetic polymorphisms, allozyme properties, and human liver genotype-phenotype correlations. Raftogianis, R.B., Wood, T.C., Weinshilboum, R.M. Biochem. Pharmacol. (1999) [Pubmed]
  8. Platelet sulfotransferase in different psychiatric disorders. Marazziti, D., Palego, L., Dell'Osso, L., Batistini, A., Cassano, G.B., Akiskal, H.S. Psychiatry research. (1996) [Pubmed]
  9. Preclinical investigation of the topical administration of phenserine: transdermal flux, cholinesterase inhibition, and cognitive efficacy. Utsuki, T., Uchimura, N., Irikura, M., Moriuchi, H., Holloway, H.W., Yu, Q.S., Spangler, E.L., Mamczarz, J., Ingram, D.K., Irie, T., Greig, N.H. J. Pharmacol. Exp. Ther. (2007) [Pubmed]
  10. Evaluation of factors of importance for clinical dementia diagnosis. Nagga, K., Garcia, J., Zetterberg, H., Blennow, K., Gottfries, J., Marcusson, J. Dementia and geriatric cognitive disorders. (2005) [Pubmed]
  11. Actions of adrenergic and cholinergic drugs on renal tubular cells. Garg, L.C. Pharmacol. Rev. (1992) [Pubmed]
  12. Pharmacogenetics of sulfotransferase. Nagata, K., Yamazoe, Y. Annu. Rev. Pharmacol. Toxicol. (2000) [Pubmed]
  13. Association between sulfotransferase 1A1 genotype and survival of breast cancer patients receiving tamoxifen therapy. Nowell, S., Sweeney, C., Winters, M., Stone, A., Lang, N.P., Hutchins, L.F., Kadlubar, F.F., Ambrosone, C.B. J. Natl. Cancer Inst. (2002) [Pubmed]
  14. Is ATP (adenosine 5'-triphosphate), like STP, a performance-enhancing additive for the tanks of cancer patients? Jatoi, A., Loprinzi, C.L., Sloan, J., Goldberg, R.M. J. Natl. Cancer Inst. (2000) [Pubmed]
  15. Biotransformation of melatonin in human breast cancer cell lines: role of sulfotransferase 1A1. Aust, S., Jaeger, W., Klimpfinger, M., Mayer, K., Baravalle, G., Ekmekcioglu, C., Thalhammer, T. J. Pineal Res. (2005) [Pubmed]
  16. Phenol sulfotransferases: hormonal regulation, polymorphism, and age of onset of breast cancer. Seth, P., Lunetta, K.L., Bell, D.W., Gray, H., Nasser, S.M., Rhei, E., Kaelin, C.M., Iglehart, D.J., Marks, J.R., Garber, J.E., Haber, D.A., Polyak, K. Cancer Res. (2000) [Pubmed]
  17. Epigenetic silencing of the sulfotransferase 1A1 gene by hypermethylation in breast tissue. Kwon, M.S., Kim, S.J., Lee, S.Y., Jeong, J.H., Lee, E.S., Kang, H.S. Oncol. Rep. (2006) [Pubmed]
  18. Genetic polymorphisms in human SULT1A1 and UGT1A1 genes associate with breast tumor characteristics: a case-series study. Shatalova, E.G., Walther, S.E., Favorova, O.O., Rebbeck, T.R., Blanchard, R.L. Breast Cancer Res. (2005) [Pubmed]
  19. Active site mutations and substrate inhibition in human sulfotransferase 1A1 and 1A3. Barnett, A.C., Tsvetanov, S., Gamage, N., Martin, J.L., Duggleby, R.G., McManus, M.E. J. Biol. Chem. (2004) [Pubmed]
  20. Characterization of human iodothyronine sulfotransferases. Kester, M.H., Kaptein, E., Roest, T.J., van Dijk, C.H., Tibboel, D., Meinl, W., Glatt, H., Coughtrie, M.W., Visser, T.J. J. Clin. Endocrinol. Metab. (1999) [Pubmed]
  21. Interactions between genetic polymorphism of cytochrome P450-1B1, sulfotransferase 1A1, catechol-o-methyltransferase and tobacco exposure in breast cancer risk. Saintot, M., Malaveille, C., Hautefeuille, A., Gerber, M. Int. J. Cancer (2003) [Pubmed]
  22. Sulfation pharmacogenetics: SULT1A1 and SULT1A2 allele frequencies in Caucasian, Chinese and African-American subjects. Carlini, E.J., Raftogianis, R.B., Wood, T.C., Jin, F., Zheng, W., Rebbeck, T.R., Weinshilboum, R.M. Pharmacogenetics (2001) [Pubmed]
  23. Human thyroid phenol sulfotransferase enzymes 1A1 and 1A3: activities in normal and diseased thyroid glands, and inhibition by thyroid hormones and phytoestrogens. Ebmeier, C.C., Anderson, R.J. J. Clin. Endocrinol. Metab. (2004) [Pubmed]
  24. Effects of dexamethasone on aryl (SULT1A1)- and hydroxysteroid (SULT2A1)-sulfotransferase gene expression in primary cultured human hepatocytes. Duanmu, Z., Locke, D., Smigelski, J., Wu, W., Dahn, M.S., Falany, C.N., Kocarek, T.A., Runge-Morris, M. Drug Metab. Dispos. (2002) [Pubmed]
  25. Curcumin is a potent inhibitor of phenol sulfotransferase (SULT1A1) in human liver and extrahepatic tissues. Vietri, M., Pietrabissa, A., Mosca, F., Spisni, R., Pacifici, G.M. Xenobiotica (2003) [Pubmed]
  26. Contribution of sulfate conjugation, deamination, and O-methylation to metabolism of dopamine and norepinephrine in human brain. Rivett, A.J., Eddy, B.J., Roth, J.A. J. Neurochem. (1982) [Pubmed]
  27. Human phenol sulfotransferase: correlation of brain and platelet activities. Young, W.F., Laws, E.R., Sharbrough, F.W., Weinshilboum, R.M. J. Neurochem. (1985) [Pubmed]
  28. Bacterial expression and kinetic characterization of the human monoamine-sulfating form of phenol sulfotransferase. Ganguly, T.C., Krasnykh, V., Falany, C.N. Drug Metab. Dispos. (1995) [Pubmed]
  29. Effects of dexamethasone on mRNA abundance of nuclear receptors and hepatic nuclear receptor target genes in neonatal calves. Greger, D.L., Blum, J.W. Journal of animal physiology and animal nutrition (2007) [Pubmed]
  30. Natural products isolated from Mexican medicinal plants: novel inhibitors of sulfotransferases, SULT1A1 and SULT2A1. Mesía-Vela, S., Sańchez, R.I., Estrada-Muñiz, E., Alavez-Solano, D., Torres-Sosa, C., Jiménez, M., Estrada, n.u.l.l., Reyes-Chilpa, R., Kauffman, F.C. Phytomedicine (2001) [Pubmed]
  31. Involvement of p38 MAPK and Nrf2 in phenolic acid-induced P-form phenol sulfotransferase expression in human hepatoma HepG2 cells. Yeh, C.T., Yen, G.C. Carcinogenesis (2006) [Pubmed]
  32. A single amino acid, glu146, governs the substrate specificity of a human dopamine sulfotransferase, SULT1A3. Dajani, R., Hood, A.M., Coughtrie, M.W. Mol. Pharmacol. (1998) [Pubmed]
  33. Use of genetically manipulated Salmonella typhimurium strains to evaluate the role of sulfotransferases and acetyltransferases in nitrofen mutagenicity. Glatt, H., Meinl, W. Carcinogenesis (2004) [Pubmed]
  34. N-Acetyltransferases, sulfotransferases and heterocyclic amine activation in the breast. Williams, J.A., Stone, E.M., Fakis, G., Johnson, N., Cordell, J.A., Meinl, W., Glatt, H., Sim, E., Phillips, D.H. Pharmacogenetics (2001) [Pubmed]
  35. Phenol sulfotransferase pharmacogenetics in humans: association of common SULT1A1 alleles with TS PST phenotype. Raftogianis, R.B., Wood, T.C., Otterness, D.M., Van Loon, J.A., Weinshilboum, R.M. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  36. Human phenol sulfotransferase STP2 gene: molecular cloning, structural characterization, and chromosomal localization. Her, C., Raftogianis, R., Weinshilboum, R.M. Genomics (1996) [Pubmed]
  37. Purification and characterization of human liver phenol-sulfating phenol sulfotransferase. Falany, C.N., Vazquez, M.E., Heroux, J.A., Roth, J.A. Arch. Biochem. Biophys. (1990) [Pubmed]
  38. Sulfotransferase (SULT) 1A1 polymorphism as a predisposition factor for lung cancer: a case-control analysis. Wang, Y., Spitz, M.R., Tsou, A.M., Zhang, K., Makan, N., Wu, X. Lung Cancer (2002) [Pubmed]
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