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Glycobiology, 2001, Vol. 11, No. 1 75-87
© 2001 Oxford University Press

Chromosomal localization and genomic organization for the galactose/ N-acetylgalactosamine/N-acetylglucosamine 6-O-sulfotransferase gene family

Stefan Hemmerich1, Jin K. Lee2, Sunil Bhakta, Annette Bistrup2, Nancy R. Ruddle3 and Steven D. Rosen2

Department of Respiratory Diseases, Roche Bioscience, Palo Alto, CA 94304, USA, 2Department of Anatomy and Program in Immunology, University of California, San Francisco, CA 94143–0452, USA, and 3Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06520–8034, USA

The galactose/N-acetylgalactosamine/N-acetylglucosamine 6-O-sulfotransferases (GSTs) are a family of Golgi-resident enzymes that transfer sulfate from 3'phosphoadenosine 5'phospho-sulfate to the 6-hydroxyl group of galactose, N-acetylgalactosamine, or N-acetylglucosamine in nascent glycoproteins. These sulfation modifications are functionally important in settings as diverse as cartilage structure and lymphocyte homing. To date six members of this gene family have been described in human and in mouse. We have determined the chromosomal localization of these genes as well as their genomic organization. While the broadly expressed enzymes implicated in proteoglycan biosynthesis are located on different chromosomes, the highly tissue specific enzymes GST-3 and 4 are encoded by genes located both in band q23.1–23.2 on chromosome 16. In the mouse, both genes reside in the syntenic region 8E1 on chromosome 8. This cross-species conserved clustering is suggestive of related functional roles for these genes. The human GST4 locus actually contains two highly similar open reading frames (ORF) that are 50 kb apart and encode two highly similar enzyme isoforms termed GST-4{alpha} and GST-4{beta}. All genes except GST0 (chondroitin 6-O-sulfotransferase) contain intron-less ORFs. With one exception these are fused directly to sequences encoding the 3' untranslated regions (UTR) of the respective mature mRNAs. The 5' UTRs of these mRNAs are usually encoded by a number of short exons 5' of the respective ORF. 5'UTRs of the same enzyme expressed in different cell types are sometimes derived from different exons located upstream of the ORF. The genomic organization of the GSTs resembles that of certain glycosyltransferase gene families.

1 To whom correspondence should be addressed at: Thios Biotechnologies, 828 Clayton Street, San Francisco, CA 94117.


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