Cloning and characterization of a close homologue of human UDP-N-acetyl- α-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase-T3, designated GalNAc-T6. Evidence for genetic but not functional redundancy

Eric Paul Bennett, Helle Hassan, Ulla Mandel, Michael A Hollingsworth, Naoaki Akisawa, Yoshito Ikematsu, Gerard Merkx, Ad Geurts Van Kessel, Sigvard Olofsson, Henrik Clausen

Research output: Contribution to journalArticle

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Abstract

The UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase, designated GalNAc-T3, exhibits unique functions. Specific acceptor substrates are used by GalNAc-T3 and not by other GalNAc-transferases. The expression pattern of GalNAc-T3 is restricted, and loss of expression is a characteristic feature of poorly differentiated pancreatic tumors. In the present study, a sixth human UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase, designated GalNAc-T6, with high similarity to GalNAc-T3, was characterized. GalNAc-T6 exhibited high sequence similarity to GalNAc-T3 throughout the coding region, in contrast to the limited similarity that exists between homologous glycosyltransferase genes, which is usually restricted to the putative catalytic domain. The genomic organizations of GALNT3 and GALNT6 are identical with the coding regions placed in 10 exons, but the genes are localized differently at 2q31 and 12q13, respectively. Acceptor substrate specificities of GalNAc-T3 and -T6 were similar and different from other GalNAc-transferases. Northern analysis revealed distinct expression patterns, which were confirmed by immunocytology using monoclonal antibodies. In contrast to GalNAc-T3, GalNAc-T6 was expressed in WI38 fibroblast cells, indicating that GalNAc-T6 represents a candidate for synthesis of oncofetal fibronectin. The results demonstrate the existence of genetic redundancy of a polypeptide GalNAc-transferase that does not provide full functional redundancy.

Original languageEnglish (US)
Pages (from-to)25362-25370
Number of pages9
JournalJournal of Biological Chemistry
Volume274
Issue number36
DOIs
StatePublished - Sep 3 1999

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Acetylgalactosamine
Uridine Diphosphate
Cloning
Redundancy
Organism Cloning
UDP-N-acetylgalactosamine polypeptide N-acetylgalactosaminyltransferase 6
polypeptide N-acetylgalactosaminyltransferase
Genes
Glycosyltransferases
Substrates
Fibroblasts
Substrate Specificity
Tumors
Exons
Catalytic Domain

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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Cloning and characterization of a close homologue of human UDP-N-acetyl- α-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase-T3, designated GalNAc-T6. Evidence for genetic but not functional redundancy. / Bennett, Eric Paul; Hassan, Helle; Mandel, Ulla; Hollingsworth, Michael A; Akisawa, Naoaki; Ikematsu, Yoshito; Merkx, Gerard; Van Kessel, Ad Geurts; Olofsson, Sigvard; Clausen, Henrik.

In: Journal of Biological Chemistry, Vol. 274, No. 36, 03.09.1999, p. 25362-25370.

Research output: Contribution to journalArticle

Bennett, Eric Paul ; Hassan, Helle ; Mandel, Ulla ; Hollingsworth, Michael A ; Akisawa, Naoaki ; Ikematsu, Yoshito ; Merkx, Gerard ; Van Kessel, Ad Geurts ; Olofsson, Sigvard ; Clausen, Henrik. / Cloning and characterization of a close homologue of human UDP-N-acetyl- α-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase-T3, designated GalNAc-T6. Evidence for genetic but not functional redundancy. In: Journal of Biological Chemistry. 1999 ; Vol. 274, No. 36. pp. 25362-25370.
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T1 - Cloning and characterization of a close homologue of human UDP-N-acetyl- α-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase-T3, designated GalNAc-T6. Evidence for genetic but not functional redundancy

AU - Bennett, Eric Paul

AU - Hassan, Helle

AU - Mandel, Ulla

AU - Hollingsworth, Michael A

AU - Akisawa, Naoaki

AU - Ikematsu, Yoshito

AU - Merkx, Gerard

AU - Van Kessel, Ad Geurts

AU - Olofsson, Sigvard

AU - Clausen, Henrik

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