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UDP-N-acetyl-?-D-galactosamine:polypeptide N-acetylgalactosaminyltransferases: completion of the family tree.


ABSTRACT: The formation of mucin-type O-glycans is initiated by an evolutionarily conserved family of enzymes, the UDP-N-acetyl-?-D-galactosamine:polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts). The human genome encodes 20 transferases; 17 of which have been characterized functionally. The complexity of the GalNAc-T family reflects the differential patterns of expression among the individual enzyme isoforms and the unique substrate specificities which are required to form the dense arrays of glycans that are essential for mucin function. We report the expression patterns and enzymatic activity of the remaining three members of the family and the further characterization of a recently reported isoform, GalNAc-T17. One isoform, GalNAcT-16 that is most homologous to GalNAc-T14, is widely expressed (abundantly in the heart) and has robust polypeptide transferase activity. The second isoform GalNAc-T18, most similar to GalNAc-T8, -T9 and -T19, completes a discrete subfamily of GalNAc-Ts. It is widely expressed and has low, albeit detectable, activity. The final isoform, GalNAc-T20, is most homologous to GalNAc-T11 but lacks a lectin domain and has no detectable transferase activity with the panel of substrates tested. We have also identified and characterized enzymatically active splice variants of GalNAc-T13 that differ in the sequence of their lectin domain. The variants differ in their affinities for glycopeptide substrates. Our findings provide a comprehensive view of the complexities of mucin-type O-glycan formation and provide insight into the underlying mechanisms employed to heavily decorate mucins and mucin-like domains with carbohydrate.

SUBMITTER: Raman J 

PROVIDER: S-EPMC3336867 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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UDP-N-acetyl-α-D-galactosamine:polypeptide N-acetylgalactosaminyltransferases: completion of the family tree.

Raman Jayalakshmi J   Guan Yu Y   Perrine Cynthia L CL   Gerken Thomas A TA   Tabak Lawrence A LA  

Glycobiology 20111220 6


The formation of mucin-type O-glycans is initiated by an evolutionarily conserved family of enzymes, the UDP-N-acetyl-α-D-galactosamine:polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts). The human genome encodes 20 transferases; 17 of which have been characterized functionally. The complexity of the GalNAc-T family reflects the differential patterns of expression among the individual enzyme isoforms and the unique substrate specificities which are required to form the dense arrays of gl  ...[more]

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