Human 3'-phosphoadenosine 5'-phosphosulfate synthetase 1 (PAPSS1) and PAPSS2

Gene cloning, characterization and chromosomal localization

Zhen Hua Xu, Diane M. Otterness, Robert Freimuth, Edward J. Carlini, Thomas C. Wood, Steve Mitchell, Eunpyo Moon, Ung Jin Kim, Jing Ping Xu, Michael J. Siciliano, Richard M Weinshilboum

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Sulfae conjugation is an important pathway in the metabolism of a large number of exogenous and endogenous compounds. These reactions are catalyzed by sulfotransferase (SULT) enzymes that utilize 3'-phosphoadenosine 5'-phosphosulfate (PAPS) as a sulfate donor. PAPS is synthesized from ATP and inorganic sulfate by PAPS synthetase (PAPSS). Two separate PAPSS cDNAs, PAPSS1 and PAPSS2, have been identified in human tissues. We have cloned and characterized the genes for human PAPSS1 and PAPSS2 to make it possible to study the pharmacogenomics of these enzymes. Both genes consisted of 12 exons with virtually identical exon-intron splice junction locations. All splice junctions conformed to the 'GT-AG' rule. The total length of PAPSS1 was approximately 108 kb, while that of PAPSS2 was greater than 37 kb. The 5'-flanking region of PAPSS1 did not include a TATA box sequence near the site of transcription initiation, but PAPSS2 had a TATA motif located 21 bp upstream from the site of transcription initiation. Northern blot analysis showed that the major PAPSS1 and PAPSS2 transcripts were approximately 2.7 and 4.2 kb in length, respectively. PAPSS1 mapped to human chromosome band 4q24 while PAPSS2 mapped to 10q22-23 by fluorescence in situ hybridization analysis. Cloning and structural characterization of PAPSS1 and PAPSS2 will make it possible to perform molecular genetic and pharmacogenomic studies of these important enzymes in humans. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)437-444
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume268
Issue number2
DOIs
StatePublished - Feb 16 2000

Fingerprint

Cloning
Ligases
Organism Cloning
Genes
Phosphoadenosine Phosphosulfate
Transcription Initiation Site
Sulfates
Exons
Enzymes
Sulfotransferases
TATA Box
PAPS synthetase
5' Flanking Region
Chromosomes
Metabolism
Human Chromosomes
Introns
Fluorescence In Situ Hybridization
Northern Blotting
Complementary DNA

Keywords

  • 3'-phosphoadenosine 5'-phosphosulfate
  • ATP sulfurylase-APS kinase
  • PAPS
  • PAPS synthetase
  • Sulfate conjugation
  • Sulfation

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Human 3'-phosphoadenosine 5'-phosphosulfate synthetase 1 (PAPSS1) and PAPSS2 : Gene cloning, characterization and chromosomal localization. / Xu, Zhen Hua; Otterness, Diane M.; Freimuth, Robert; Carlini, Edward J.; Wood, Thomas C.; Mitchell, Steve; Moon, Eunpyo; Kim, Ung Jin; Xu, Jing Ping; Siciliano, Michael J.; Weinshilboum, Richard M.

In: Biochemical and Biophysical Research Communications, Vol. 268, No. 2, 16.02.2000, p. 437-444.

Research output: Contribution to journalArticle

Xu, Zhen Hua ; Otterness, Diane M. ; Freimuth, Robert ; Carlini, Edward J. ; Wood, Thomas C. ; Mitchell, Steve ; Moon, Eunpyo ; Kim, Ung Jin ; Xu, Jing Ping ; Siciliano, Michael J. ; Weinshilboum, Richard M. / Human 3'-phosphoadenosine 5'-phosphosulfate synthetase 1 (PAPSS1) and PAPSS2 : Gene cloning, characterization and chromosomal localization. In: Biochemical and Biophysical Research Communications. 2000 ; Vol. 268, No. 2. pp. 437-444.
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abstract = "Sulfae conjugation is an important pathway in the metabolism of a large number of exogenous and endogenous compounds. These reactions are catalyzed by sulfotransferase (SULT) enzymes that utilize 3'-phosphoadenosine 5'-phosphosulfate (PAPS) as a sulfate donor. PAPS is synthesized from ATP and inorganic sulfate by PAPS synthetase (PAPSS). Two separate PAPSS cDNAs, PAPSS1 and PAPSS2, have been identified in human tissues. We have cloned and characterized the genes for human PAPSS1 and PAPSS2 to make it possible to study the pharmacogenomics of these enzymes. Both genes consisted of 12 exons with virtually identical exon-intron splice junction locations. All splice junctions conformed to the 'GT-AG' rule. The total length of PAPSS1 was approximately 108 kb, while that of PAPSS2 was greater than 37 kb. The 5'-flanking region of PAPSS1 did not include a TATA box sequence near the site of transcription initiation, but PAPSS2 had a TATA motif located 21 bp upstream from the site of transcription initiation. Northern blot analysis showed that the major PAPSS1 and PAPSS2 transcripts were approximately 2.7 and 4.2 kb in length, respectively. PAPSS1 mapped to human chromosome band 4q24 while PAPSS2 mapped to 10q22-23 by fluorescence in situ hybridization analysis. Cloning and structural characterization of PAPSS1 and PAPSS2 will make it possible to perform molecular genetic and pharmacogenomic studies of these important enzymes in humans. (C) 2000 Academic Press.",
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T1 - Human 3'-phosphoadenosine 5'-phosphosulfate synthetase 1 (PAPSS1) and PAPSS2

T2 - Gene cloning, characterization and chromosomal localization

AU - Xu, Zhen Hua

AU - Otterness, Diane M.

AU - Freimuth, Robert

AU - Carlini, Edward J.

AU - Wood, Thomas C.

AU - Mitchell, Steve

AU - Moon, Eunpyo

AU - Kim, Ung Jin

AU - Xu, Jing Ping

AU - Siciliano, Michael J.

AU - Weinshilboum, Richard M

PY - 2000/2/16

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N2 - Sulfae conjugation is an important pathway in the metabolism of a large number of exogenous and endogenous compounds. These reactions are catalyzed by sulfotransferase (SULT) enzymes that utilize 3'-phosphoadenosine 5'-phosphosulfate (PAPS) as a sulfate donor. PAPS is synthesized from ATP and inorganic sulfate by PAPS synthetase (PAPSS). Two separate PAPSS cDNAs, PAPSS1 and PAPSS2, have been identified in human tissues. We have cloned and characterized the genes for human PAPSS1 and PAPSS2 to make it possible to study the pharmacogenomics of these enzymes. Both genes consisted of 12 exons with virtually identical exon-intron splice junction locations. All splice junctions conformed to the 'GT-AG' rule. The total length of PAPSS1 was approximately 108 kb, while that of PAPSS2 was greater than 37 kb. The 5'-flanking region of PAPSS1 did not include a TATA box sequence near the site of transcription initiation, but PAPSS2 had a TATA motif located 21 bp upstream from the site of transcription initiation. Northern blot analysis showed that the major PAPSS1 and PAPSS2 transcripts were approximately 2.7 and 4.2 kb in length, respectively. PAPSS1 mapped to human chromosome band 4q24 while PAPSS2 mapped to 10q22-23 by fluorescence in situ hybridization analysis. Cloning and structural characterization of PAPSS1 and PAPSS2 will make it possible to perform molecular genetic and pharmacogenomic studies of these important enzymes in humans. (C) 2000 Academic Press.

AB - Sulfae conjugation is an important pathway in the metabolism of a large number of exogenous and endogenous compounds. These reactions are catalyzed by sulfotransferase (SULT) enzymes that utilize 3'-phosphoadenosine 5'-phosphosulfate (PAPS) as a sulfate donor. PAPS is synthesized from ATP and inorganic sulfate by PAPS synthetase (PAPSS). Two separate PAPSS cDNAs, PAPSS1 and PAPSS2, have been identified in human tissues. We have cloned and characterized the genes for human PAPSS1 and PAPSS2 to make it possible to study the pharmacogenomics of these enzymes. Both genes consisted of 12 exons with virtually identical exon-intron splice junction locations. All splice junctions conformed to the 'GT-AG' rule. The total length of PAPSS1 was approximately 108 kb, while that of PAPSS2 was greater than 37 kb. The 5'-flanking region of PAPSS1 did not include a TATA box sequence near the site of transcription initiation, but PAPSS2 had a TATA motif located 21 bp upstream from the site of transcription initiation. Northern blot analysis showed that the major PAPSS1 and PAPSS2 transcripts were approximately 2.7 and 4.2 kb in length, respectively. PAPSS1 mapped to human chromosome band 4q24 while PAPSS2 mapped to 10q22-23 by fluorescence in situ hybridization analysis. Cloning and structural characterization of PAPSS1 and PAPSS2 will make it possible to perform molecular genetic and pharmacogenomic studies of these important enzymes in humans. (C) 2000 Academic Press.

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KW - PAPS synthetase

KW - Sulfate conjugation

KW - Sulfation

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