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Research ArticleArticle

Expression of the Orphan Cytosolic Sulfotransferase SULT1C3 in Human Intestine: Characterization of the Transcript Variant and Implications for Function

Zofia Duniec-Dmuchowski, Elizabeth A. Rondini, Zachary E. Tibbs, Charles N. Falany, Melissa Runge-Morris and Thomas A. Kocarek
Drug Metabolism and Disposition March 2014, 42 (3) 352-360; DOI: https://doi.org/10.1124/dmd.113.055665
Zofia Duniec-Dmuchowski
Institute of Environmental Health Sciences, Wayne State University, Detroit, Michigan (Z.D.-D., E.A.R., M.R.-M., T.A.K.); and Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, Alabama, (Z.E.T., C.N.F.)
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Elizabeth A. Rondini
Institute of Environmental Health Sciences, Wayne State University, Detroit, Michigan (Z.D.-D., E.A.R., M.R.-M., T.A.K.); and Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, Alabama, (Z.E.T., C.N.F.)
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Zachary E. Tibbs
Institute of Environmental Health Sciences, Wayne State University, Detroit, Michigan (Z.D.-D., E.A.R., M.R.-M., T.A.K.); and Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, Alabama, (Z.E.T., C.N.F.)
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Charles N. Falany
Institute of Environmental Health Sciences, Wayne State University, Detroit, Michigan (Z.D.-D., E.A.R., M.R.-M., T.A.K.); and Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, Alabama, (Z.E.T., C.N.F.)
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Melissa Runge-Morris
Institute of Environmental Health Sciences, Wayne State University, Detroit, Michigan (Z.D.-D., E.A.R., M.R.-M., T.A.K.); and Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, Alabama, (Z.E.T., C.N.F.)
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Thomas A. Kocarek
Institute of Environmental Health Sciences, Wayne State University, Detroit, Michigan (Z.D.-D., E.A.R., M.R.-M., T.A.K.); and Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, Alabama, (Z.E.T., C.N.F.)
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This article has a correction. Please see:

  • Correction to “Expression of the Orphan Cytosolic Sulfotransferase SULT1C3 in Human Intestine: Characterization of the Transcript Variant and Implications for Function” - May 01, 2014

Abstract

The cystolic sulfotransferse 1C3 (SULT1C3) gene was identified by computational analysis of the human genome and suggested to contain duplications of its last two exons (7a/b and 8a/b). Although the SULT1C3 isoform containing the more downstream exons 7b and 8b (SULT1C3d) has been expressed in Escherichia coli, crystallized, and characterized for activity, there is currently no evidence that SULT1C3 is expressed in any human tissue. Using reverse-transcription polymerase chain reaction, we detected SULT1C3 mRNA in the colorectal adenocarcinoma cell line (LS180), colon, and small intestine, but the amplified fragment contained the more upstream exons 7a and 8a. 3′-Rapid amplification of cDNA ends (RACE) confirmed that the SULT1C3 transcript expressed in LS180 cells contained exons 7a/8a, whereas 5′-RACE identified a noncoding exon 1. Full-length SULT1C3 transcript containing exons 7a/8a was amplified from LS180 and intestinal RNA, and in vitro transcription-translation of the cloned cDNA indicated that translation primarily began at the first of three in-frame ATG codons. Since SULT1C3 containing exons 7a/8a (SULT1C3a) would differ by 30 amino acids from SULT1C3d containing exons 7b/8b, we considered the functional implications of expressing one or the other isoform by generating structural models based on the reported crystal structure for SULT1C3d. Comparison of the structures indicated that five of the residues forming the substrate-binding pocket differed between the two isoforms, resulting in a change in both electron density and charge distribution along the inner wall of the substrate-binding pocket. These data indicate that SULT1C3 is expressed in human intestine but suggest that the expressed isoform is likely to differ functionally from the isoform that has been previously characterized.

Footnotes

    • Received October 30, 2013.
    • Accepted December 11, 2013.
  • This research was supported by the National Institutes of Health National Heart, Lung, and Blood Institute [Grant R01 HL050710] (to T.A.K.); the National Institutes of Health National Institute of Environmental Health Sciences [Grant R01 ES005823] (to M.R.-M.); and the National Institutes of Health National Institute of General Medical Sciences [Grant R01 GM038953] (to C.N.F.).

  • dx.doi.org/10.1124/dmd.113.055665.

  • Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 42 (3)
Drug Metabolism and Disposition
Vol. 42, Issue 3
1 Mar 2014
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Research ArticleArticle

Characterization of the Human Intestinal SULT1C3 Transcript

Zofia Duniec-Dmuchowski, Elizabeth A. Rondini, Zachary E. Tibbs, Charles N. Falany, Melissa Runge-Morris and Thomas A. Kocarek
Drug Metabolism and Disposition March 1, 2014, 42 (3) 352-360; DOI: https://doi.org/10.1124/dmd.113.055665

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Research ArticleArticle

Characterization of the Human Intestinal SULT1C3 Transcript

Zofia Duniec-Dmuchowski, Elizabeth A. Rondini, Zachary E. Tibbs, Charles N. Falany, Melissa Runge-Morris and Thomas A. Kocarek
Drug Metabolism and Disposition March 1, 2014, 42 (3) 352-360; DOI: https://doi.org/10.1124/dmd.113.055665
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