InterPro domain: IPR040911

In addition to a b-glucuronyltransferase domain, exostosins contain anadditional alpha 1,4-N-acetylglucosaminyltransferase domain that belongs to family GT64 [ 1 , 2 ]. Activities of both exostosin GT domains are required for synthesizing the backbone of glycosaminoglycan, heparan sulfate. In plants, many genes have been shown to encode proteins with significant sequence similarity to the exostosinb-glucuronyltransferase domain and therefore are grouped into family GT47 [ 3 ]. This entry represents the GT47 domain of exostosins.

There are five identified human EXT family proteins (EXT1, EXT2, EXTL1, EXTL2 and EXTL3), which are members of the hereditary multiple exostoses family of tumor suppressors [ 4 ]. They are glycosyltransferases required for the biosynthesis of heparan sulfate. Hereditary multiple exostoses (EXT) is an autosomal dominant disorder that is characterised by the appearance of multiple outgrowths of the long bones (exostoses) at their epiphyses [ 5 ]. Mutations in two homologous genes, EXT1 and EXT2, are responsible for the EXT syndrome. The human and mouse EXT genes have at least two homologues in the invertebrate Caenorhabditis elegans, indicating that they do not function exclusively as regulators of bone growth. EXT1 and EXT2 have both been shown to encode glycosyltransferases involved in the chain elongation step of heparan sulphate biosynthesis [ 6 ].

1. The putative tumor suppressors EXT1 and EXT2 are glycosyltransferases required for the biosynthesis of heparan sulfate. J. Biol. Chem. 273, 26265-8
2. Location of the glucuronosyltransferase domain in the heparan sulfate copolymerase EXT1 by analysis of Chinese hamster ovary cell mutants. J. Biol. Chem. 275, 27733-40
3. Unraveling the functions of glycosyltransferase family 47 in plants. Trends Plant Sci. 8, 565-8
4. Expression of rib-1, a Caenorhabditis elegans homolog of the human tumor suppressor EXT genes, is indispensable for heparan sulfate synthesis and embryonic morphogenesis. J. Biol. Chem. 282, 8533-44
5. Structure, chromosomal location, and expression profile of EXTR1 and EXTR2, new members of the multiple exostoses gene family. Biochem. Biophys. Res. Commun. 243, 61-6