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

ABSTRACT

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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Abbreviations

HMM:

hidden Markov model

MTC:

multiple tissue cDNA

ORF:

open reading frame

PAPS:

3′-phosphoadenosine-5′-phosphosulfate

RACE:

rapid amplification of cDNA ends

SULT:

sulfotransferase

UTR:

untranslated region

References

  1. Weinshilboum R, Otterness D . Conjugation–deconjugation reactions in drug metabolism and toxicity. Chapter 2, Sulfotransferase enzymes. In: Kauffman FC (ed) Handbook of Experimental Pharmacology Series, Vol 112 Springer-Verlag: Berlin, Heidelberg 1994; pp 45–78.

    Google Scholar 

  2. Falany CN . Enzymology of human cytosolic sulfotransferases. FASEB J 1997; 11: 206–216.

    Article  CAS  PubMed  Google Scholar 

  3. Weinshilboum RM, Otterness DM, Aksoy IA, Wood TC, Her C, Raftogianis RB . Sulfotransferase molecular biology: cDNAs and genes. FASEB J 1997; 11: 3–14.

    Article  CAS  PubMed  Google Scholar 

  4. Komatsu K, Driscoll WJ, Koh Y, Strott CA . A P-loop related motif (GxxGxxK) highly conserved in sulfotransferases is required for binding the activated sulfate donor. Biochem Biophys Res Commun 1994; 204: 1178–1185.

    Article  CAS  PubMed  Google Scholar 

  5. Driscoll WJ, Komatsu K, Strott CA . Proposed active site domain in estrogen sulfotransferase as determined by mutational analysis. Proc Natl Acad Sci USA 1995; 92: 12328–12332.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Marsolais F, Varin L . Identification of amino acid residues critical for catalysis and cosubstrate binding in the flavonol 3-sulfotransferase. J Biol Chem 1995; 270: 30458–30463.

    Article  CAS  PubMed  Google Scholar 

  7. Petrotchenko EV, Pedersen LC, Borchers CH, Tomer KB, Negishi M . The dimerization motif of cytosolic sulfotransferases. FEBS Let 2001; 490: 39–43.

    Article  CAS  Google Scholar 

  8. Raftogianis RB, Freimuth RR, Buck J, Weinshilboum RM, Coughtrie MWH . A proposed nomenclature system for the cytosolic sulfotransferase (SULT) superfamily. 2004; Pharmacogenetics in press.

  9. Negishi M, Pedersen LG, Petrotchenko E, Shevtsov S, Gorokhov A, Kakuta Y et al. Structure and function of sulfotransferases. Arch Biochem Biophys 2001; 390: 149–157.

    Article  CAS  PubMed  Google Scholar 

  10. Fujita K, Nagata K, Ozawa S, Sasano H, Yamazoe Y . Molecular cloning and characterization of rat ST1B1 and human ST1B2 cDNAs, encoding thyroid hormone sulfotransferases. J Biochem 1997; 122: 1052–1061.

    Article  CAS  PubMed  Google Scholar 

  11. Her C, Kaur GP, Athwal RS, Weinshilboum RM . Human sulfotransferase SULT1C1: cDNA cloning, tissue-specific expression, and chromosomal localization. Genomics 1997; 41: 467–470.

    Article  CAS  PubMed  Google Scholar 

  12. Her C, Wood TC, Eichler EE, Mohrenweiser HW, Ramagli LS, Siciliano MJ et al. Human hydroxysteroid sulfotransferase SULT2B1: two enzymes encoded by a single chromosome 19 gene. Genomics 1998; 53: 284–295.

    Article  CAS  PubMed  Google Scholar 

  13. Sakakibara Y, Yanagisawa K, Katafuchi J, Ringer DP, Takami Y, Nakayama T et al. Molecular cloning, expression, and characterization of novel human SULT1C sulfotransferases that catalyze the sulfonation of N-hydroxy-2-acetylaminofluorene. J Biol Chem 1998; 273: 33929–33935.

    Article  CAS  PubMed  Google Scholar 

  14. Wang J, Falany JL, Falany CN . Expression and characterization of a novel thyroid hormone-sulfating form of cytosolic sulfotransferase from human liver. Mol Pharmacol 1998; 53: 274–282.

    Article  CAS  PubMed  Google Scholar 

  15. Falany CN, Xie X, Wang J, Ferrer J, Falany JL . Molecular cloning and expression of novel sulphotransferase-like cDNAs from human and rat brain. Biochem J 2000; 346: 857–864.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Aksoy IA, Weinshilboum RM . Human thermolabile phenol sulfotransferase gene (STM): molecular cloning and structural characterization. Biochem Biophys Res Commun 1995; 208: 786–795.

    Article  CAS  PubMed  Google Scholar 

  17. Her C, Aksoy IA, Kimura S, Brandriff BF, Wasmuth JJ, Weinshilboum RM . Human estrogen sulfotransferase gene (STE): cloning, structure, and chromosomal localization. Genomics 1995; 29: 16–23.

    Article  CAS  PubMed  Google Scholar 

  18. Otterness DM, Her C, Aksoy S, Kimura S, Wieben ED, Weinshilboum RM . Human dehydroepiandrosterone sulfotransferase gene: molecular cloning and structural characterization. DNA Cell Biol 1995; 14: 331–341.

    Article  CAS  PubMed  Google Scholar 

  19. Her C, Raftogianis R, Weinshilboum RM . Human phenol sulfotransferase STP2 gene: molecular cloning, structural characterization, and chromosomal localization. Genomics 1996; 33: 409–420.

    Article  CAS  PubMed  Google Scholar 

  20. Raftogianis RB, Her C, Weinshilboum RM . Human phenol sulfotransferase pharmacogenetics: STP1 gene cloning and structural characterization. Pharmacogenetics 1996; 6: 473–487.

    Article  CAS  PubMed  Google Scholar 

  21. Freimuth RR, Raftogianis RB, Wood TC, Moon E, Kim U-J, Xu J et al. Human sulfotransferases SULT1C1 and SULT1C2: cDNA characterization, gene cloning, and chromosomal localization. Genomics 2000; 65: 157–165.

    Article  CAS  PubMed  Google Scholar 

  22. Meinl W, Glatt H . Structure and localization of the human SULT1B1 gene: neighborhood to SULT1E1 and a SULT1D pseudogene. Biochem Biophys Res Commun 2001; 288: 855–862.

    Article  CAS  PubMed  Google Scholar 

  23. Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ . Basic local alignment search tool. J Mol Biol 1990; 215: 403–410.

    Article  CAS  PubMed  Google Scholar 

  24. Eddy SR HMMER: Profile Hidden Markov Models for Biological Sequence Analysis 2001. http://hmmer.wustl.edu.

  25. Birney E, Copley R Wise2 Software Package 2001. http://www.ebi.ac.uk/Wise2/.

  26. Eddy SR . Profile hidden Markov models. Bioinformatics 1998; 14: 755–763.

    Article  CAS  PubMed  Google Scholar 

  27. Kozak M . An analysis of 5′-noncoding sequences from 699 vertebrate messenger RNAs. Nucleic Acids Res 1987; 15: 8125–8148.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Twigg SRF, Burns HD, Oldridge M, Heath JK, Wilkie AOM . Conserved use of a non-canonical 5′ splice site (/GA) in alternative splicing by fibroblast growth factor receptors 1, 2 and 3. Hum Molec Genet 1998; 7: 685–691.

    Article  CAS  PubMed  Google Scholar 

  29. Burset M, Seledtsov IA, Solovyev VV . Analysis of canonical and non-canonical splice sites in mammalian genomes. Nucleic Acids Res 2000; 28: 4364–4375.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Tarn W-Y, Steitz JA . A novel spliceosome containing U11, U12, and U5 snRNPs excises a minor class (AT–AC) intron in vitro. Cell 1996; 84: 801–811.

    Article  CAS  PubMed  Google Scholar 

  31. Reveley AM, Carter SMB, Reveley MA, Sandler M . A genetic study of platelet phenolsulfotransferase activity in normal and schizophrenic twins. J Psychiatr Res 1982/1983; 17: 303–307.

    Article  PubMed  Google Scholar 

  32. Price RA, Cox NJ, Spielman RS, Van Loon J, Maidak BL, Weinshilboum RM . Inheritance of human platelet thermolabile phenol sulfotransferase (TL PST) activity. Genet Epidemiol 1988; 5: 1–15.

    Article  CAS  PubMed  Google Scholar 

  33. Price RA, Spielman RS, Lucena AL, Van Loon JA, Maidak BL, Weinshilboum RM . Genetic polymorphism for human platelet thermostable phenol sulfotransferase (TS PST) activity. Genetics 1989; 122: 905–914.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Raftogianis RB, Wood TC, Otterness DM, Van Loon JA, Weinshilboum RM . Phenol sulfotransferase pharmacogenetics in humans: association of common SULT1A1 alleles with TS PST phenotype. Biochem Biophys Res Commun 1997; 239: 298–304.

    Article  CAS  PubMed  Google Scholar 

  35. Thomae BA, Rifki OF, Theobald MA, Eckloff BW, Wieben ED, Weinshilboum RM . Human catecholamine sulfotransferase (SULT1A3) pharmacogenetics: common functional genetic polymorphism. J Neurochem 2003; 87: 809–819.

    Article  CAS  PubMed  Google Scholar 

  36. Adjei AA, Thomae BA, Prondzinski JL, Eckloff BW, Wieben ED, Weinshilboum RM . Human estrogen sulfotransferase (SULT1E1) pharmacogenomics: gene resequencing and functional genomics. Br J Pharmacol 2003; 139: 1373–1382.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Thomae BA, Eckloff BW, Freimuth RR, Wieben ED, Weinshilboum RM . Human sulfotransferase SULT2A1 pharmacogenetics: genotype-to-phenotype studies. Pharmacogenomics J 2002; 2: 48–56.

    Article  CAS  PubMed  Google Scholar 

  38. Nowell S, Sweeney C, Winters M, Stone A, Lang NP, Hutchins LF et al. Association between sulfotransferase 1A1 genotype and survival of breast cancer patients receiving tamoxifen therapy. J Natl Cancer Inst 2002; 94: 1635–1640.

    Article  CAS  PubMed  Google Scholar 

  39. Nagata K, Yoshinari K, Ozawa S, Yamazoe Y . Arylamine activating sulfotransferase in liver. Mutat Res 1997; 376: 267–272.

    Article  CAS  PubMed  Google Scholar 

  40. Wilborn TW, Comer KA, Dooley TP, Reardon IM, Heinrikson RL, Falany CN . Sequence analysis and expression of the cDNA for the phenol-sulfating form of human liver phenol sulfotransferase. Mol Pharmacol 1993; 43: 70–77.

    CAS  PubMed  Google Scholar 

  41. Zhu X, Veronese ME, Iocco P, McManus ME . cDNA cloning and expression of a new form of human aryl sulfotransferase. Int J Biochem Cell Biol 1996; 28: 565–571.

    Article  CAS  PubMed  Google Scholar 

  42. Zhu X, Veronese ME, Bernard CC, Sansom LN, McManus ME . Identification of two human brain aryl sulfotransferase cDNAs. Biochem Biophys Res Commun 1993; 195: 120–127.

    Article  CAS  PubMed  Google Scholar 

  43. Wang J, Falany JL, Falany CN . Expression and characterization of a novel thyroid hormone-sulfating form of cytosolic sulfotransferase from human liver. Mol Pharmacol 1998; 53: 274–282.

    Article  CAS  PubMed  Google Scholar 

  44. Sakakibara Y, Yanagisawa K, Katafuchi J, Ringer DP, Takami Y, Nakayama T et al. Molecular cloning, expression, and characterization of novel human SULT1C sulfotransferases that catalyze the sulfonation of N-hydroxy-2-acetylaminofluorene. J Biol Chem 1998; 273: 33929–33935.

    Article  CAS  PubMed  Google Scholar 

  45. Aksoy IA, Wood TC, Weinshilboum R . Human liver estrogen sulfotransferase: identification by cDNA cloning and expression. Biochem Biophys Res Commun 1994; 200: 1621–1629.

    Article  CAS  PubMed  Google Scholar 

  46. Otterness DM, Wieben ED, Wood TC, Watson WG, Madden BJ, McCormick DJ et al. Human liver dehydroepiandrosterone sulfotransferase: molecular cloning and expression of cDNA. Mol Pharmacol 1992; 41: 865–872.

    CAS  PubMed  Google Scholar 

  47. Falany CN, Xie X, Wang J, Ferrer J, Falany JL . Molecular cloning and expression of novel sulphotransferase-like cDNAs from human and rat brain. Biochem J 2000; 346: 857–864.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Sakakibara Y, Yanagisawa K, Takami Y, Nakayama T, Suiko M, Liu MC . Molecular cloning, expression, and functional characterization of novel mouse sulfotransferases. Biochem Biophys Res Commun 1998; 247: 681–686.

    Article  CAS  PubMed  Google Scholar 

  49. Cao H, Agarwal SK, Burnside J . Cloning and expression of a novel chicken sulfotransferase cDNA regulated by GH. J Endocrinol 1999; 160: 491–500.

    Article  CAS  PubMed  Google Scholar 

  50. Sonnhammer EL, Eddy SR, Durbin R . Pfam: a comprehensive database of protein domain families based on seed alignments. Proteins 1997; 28: 405–420.

    Article  CAS  PubMed  Google Scholar 

  51. Bateman A, Birney E, Cerruti L, Durbin R, Etwiller L, Eddy SR et al. The Pfam protein families database. Nucleic Acids Res 2002; 30: 276–280.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Devereux J, Haeberli P, Smithies O . A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res 1984; 12: 387–395.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Boguski MS, Lowe TM, Tolstoshev CM . dbEST—database for ‘expressed sequence tags’. Nat Genet 1993; 4: 332–333.

    Article  CAS  PubMed  Google Scholar 

  54. Ho SN, Hunt HD, Horton RM, Pullen JK, Pease LR . Site-directed mutagenesis by overlap extension using the polymerase chain reaction. Gene 1989; 77: 51–59.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank Luanne Wussow for her assistance with the preparation of this manuscript, Michael Heldebrant and Harold Solbrig for their assistance with the GeneWise program, and Dr Rebecca Raftogianis Blanchard, Emily Aaronson, Richard Hwang, and Ray Mak for their contributions to the preliminary experimental characterization of novel genes. This work was supported in part by NIH grants RO1 GM35720 (RMW), UO1 GM61388 (RMW, CGC, EDW), and the Washington University Genome Analysis Training Program (NIH T32-HG00045) (RRF).

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Correspondence to R M Weinshilboum.

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DUALITY OF INTEREST

Dr.Weinshilboum has either provided consulting services or presented seminars at Abbott Laboratories, Bristol-Myers Squibb, Eli Lilly, Johnson and Johnson, Roche and Merck, Inc. All fees and honoraria for these services and/or seminars were paid to Mayo Foundation. In addition, Drs. Wieben and Weinshilboum currently hold a peer-reviewed grant from Eli Lilly.

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Freimuth, R., Wiepert, M., Chute, C. et al. Human cytosolic sulfotransferase database mining: identification of seven novel genes and pseudogenes. Pharmacogenomics J 4, 54–65 (2004). https://doi.org/10.1038/sj.tpj.6500223

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