Control of O-glycan branch formation: Molecular cloning of human cDNA encoding a novel β1,6-N-acetylglucosaminyltransferase forming core 2 and core 4

Tilo Schwientek, Mitsuharu Nomoto, Steven B. Levery, Gerard Merkx, Ad Geurts Van Kessel, Eric P. Bennett, Michael A. Hollingsworth, Henrik Clausen

Research output: Contribution to journalArticle

92 Scopus citations

Abstract

A novel human UDP-GlcNAc:Gal/GlcNAcβ1-3GalNAcα β1,6GlcNAc- transferase, designated C2/4GnT, was identified by BLAST analysis of expressed sequence tags. The sequence of C2/4GnT encoded a putative type II transmembrane protein with significant sequence similarity to human C2GnT and IGnT. Expression of the secreted form of C2/4GnT in insect cells showed that the gene product had UDP-N-acetyl-α-D-glucosamine:acceptor β1,6-N- acetylglucosaminyltransferase (β1,6GlcNAc-transferase) activity. Analysis of substrate specificity revealed that the enzyme catalyzed O-glycan branch formation of the core 2 and core 4 type. NMR analyses of the product formed with core 3-para-nitrophenyl confirmed the product core 4-para-nitrophenyl. The coding region of C2/4GnT was contained in a single exon and located to chromosome 15q21.3. Northern analysis revealed a restricted expression pattern of C2/4GnT mainly in colon, kidney, pancreas, and small intestine. No expression of C2/4GnT was detected in brain, heart, liver, ovary, placenta, spleen, thymus, and peripheral blood leukocytes. The expression of core 2 O- glycans has been correlated with cell differentiation processes and cancer. The results confirm the predicted existence of a β1,6GlcNAc-transferase that functions in both core 2 and core 4 O-glycan branch formation. The redundancy in β1,6GlcNAc-transferases capable of forming core 2 O-glycans is important for understanding the mechanisms leading to specific changes in core 2 branching during cell development and malignant transformation.

Original languageEnglish (US)
Pages (from-to)4504-4512
Number of pages9
JournalJournal of Biological Chemistry
Volume274
Issue number8
DOIs
StatePublished - Feb 19 1999

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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