Molecular Cloning and Characterization of a Dermatan-specific N-Acetylgalactosamine 4-O-Sulfotransferase

Mathias R. Evers, Guoqing Xia, Hyung Gyoo Kang, Melitta Schachner, Jacques U. Baenziger

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Abstract

We have identified and characterized an N-acetyl-galactosamine-4-O-sulfotransferase designated dermatan-4-sulfotransferase-1 (D4ST-1) (GenBank™ accession number AF401222) based on its homology to HNK-1 sulfotransferase. The cDNA predicts an open reading frame encoding a type II membrane protein of 376 amino acids with a 43-amino acid cytoplasmic domain and a 316-amino acid luminal domain containing two potential N-linked glycosylation sites. D4ST-1 has significant amino acid identity with HNK-1 sulfotrans. ferase (21.4%), N-acetylgalactosamine-4-O-sulfotransferase 1 (GalNAc-4-ST1) (24.7%), N-acetylgalactosamine-4-O-sulfotransferase 2 (GalNAc-4-ST2) (21.0%), chondroitin-4-O-sulfotransferase 1 (27.3%), and chondroitin-4-O-sulfotransferase 2 (22.8%). D4ST-1 transfers sulfate to the C-4 hydroxyl of β1,4-linked GalNAc that is substituted with an α-linked iduronic acid (IdoUA) at the C-3 hydroxyl. D4ST-1 shows a strong preference in vitro for sulfate transfer to IdoUAα1,3GalNAcβ1,4 that is flanked by GlcUAβ1,3GalNAcβ1,4 as compared with IdoUAα1, 3GalNAcβ1,4 flanked by IdoUAα1,3GalNAcβ1,4. The specificity of D4ST-1 when assayed in vitro suggests that the addition of sulfate to GalNAc occurs immediately after epimerization of GlcUA to IdoUA. The open reading frame of D4ST-1 is encoded by a single exon located on human chromosome 15q14. Northern blot analysis reveals a single 2.4-kilobase transcript. D4ST-1 message is expressed in virtually all tissues at some level but is most highly expressed in pituitary, placenta, uterus, and thyroid. The properties of D4ST-1 indicate that sulfation of the GalNAc moieties in dermatan is mediated by a distinct GalNAc-4-O-sulfotransferase and occurs following epimerization of GlcUA to IdoUA.

Original languageEnglish (US)
Pages (from-to)36344-36353
Number of pages10
JournalJournal of Biological Chemistry
Volume276
Issue number39
DOIs
StatePublished - Sep 28 2001
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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