Elsevier

Genomics

Volume 65, Issue 2, 15 April 2000, Pages 157-165
Genomics

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

https://doi.org/10.1006/geno.2000.6150Get rights and content

Abstract

Sulfate conjugation catalyzed by sulfotransferase (SULT) enzymes is an important pathway in the biotransformation of many drugs, other xenobiotics, neurotransmitters, and hormones. We previously described a human cDNA, SULT1C1, that encoded a protein similar in sequence to that of rat ST1C1. Subsequently, a related human cDNA, SULT1C2, was reported. In the present study, we set out to characterize further the human SULT1C1 cDNA and then to clone, structurally characterize, and map its gene. As an initial step, we performed 5′- and 3′-RACE with SULT1C1 cDNA. Those experiments demonstrated that a small number of SULT1C1 transcripts contained an “insert,” which we later showed resulted from alternative splicing that involved an Alu sequence in intron 3 of SULT1C1. We then cloned and structurally characterized the SULT1C1 gene from a human genomic BAC library. Because the sequence of SULT1C2 was closely related to that of SULT1C1 and because the genes for other human SULT paralogues occur in clusters, we screened the BAC clones that had been positive for SULT1C1 to search for SULT1C2 and discovered a clone that contained both genes. That BAC was used to sequence and structurally characterize SULT1C2. SULT1C1 and SULT1C2 were approximately 21 and 10 kb in length, respectively. Both genes contained seven exons that encoded protein, and both had structures that were similar to those of other genes that encode members of the SULT1 family. Finally, human SULT1C1 and SULT1C2 mapped to 2q11.2 by fluorescence in situ hybridization. The cloning and structural characterization of SULT1C1 and SULT1C2 will now make it possible to perform molecular genetic and pharmacogenomic studies of these sulfate-conjugating enzymes in humans.

References (46)

  • C. Her et al.

    Human sulfotransferase SULT1C1: cDNA cloning, tissue-specific expression, and chromosomal localization

    Genomics

    (1997)
  • C. Her et al.

    Human hydroxysteroid sulfotransferase SULT2B1: Two enzymes encoded by a single chromosome 19 gene

    Genomics

    (1998)
  • S.N. Ho et al.

    Site-directed mutagenesis by overlap extension using the polymerase chain reaction

    Gene

    (1989)
  • U.-J. Kim et al.

    Construction and characterization of a human bacterial artificial chromosome library

    Genomics

    (1996)
  • P. Liu et al.

    Dual Alu-PCR primers and conditions for isolation of human chromosome painting probes from hybrid cells

    Cancer Genet. Cytogenet.

    (1993)
  • P. Marlton et al.

    Molecular characterization of 16p deletions associated with inversion 16 defines the critical fusion for leukemogenesis

    Blood

    (1995)
  • J.A. Miller

    Sulfonation in chemical carcinogenesis—History and present status

    Chem. Biol. Interact.

    (1994)
  • K. Nagata et al.

    Isolation and expression of a cDNA encoding a male-specific rat sulfotransferase that catalyzes activation of N-hydroxy-2-acetylaminofluorene

    J. Biol. Chem.

    (1993)
  • Y. Sakakibara 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)
  • S.T. Smale et al.

    The “initiator” as a transcription control element

    Cell

    (1989)
  • T.C. Wood et al.

    Human liver thermolabile phenol sulfotransferase: cDNA cloning, expression and characterization

    Biochem. Biophys. Res. Commun.

    (1994)
  • T.C. Wood et al.

    Human dehydroepiandrosterone sulfotransferase pharmacogenetics: Quantitative Western analysis and gene sequence polymorphisms

    J. Steroid Biochem. Mol. Biol.

    (1996)
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    Sequence data from this article have been deposited with the EMBL/GenBank Data Libraries under Accession Nos. AF186251–AF186256 (SULT1C1 cDNA), AF186257–AF186262 (SULT1C1 gene), and AF186263 (SULT1C2 gene).

    1

    Present address: Department of Pharmacology, Fox Chase Cancer Center, Philadelphia, PA 19111.

    2

    To whom correspondence and reprint requests should be addressed. Telephone: (507) 284-2246. Fax: (507) 284-9111. E-mail: [email protected].

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