EXTL2

EXTL2 encodes exostosin-like glycosyltransferase 2. This gene belongs to the multiple exostoses (EXT) family and is involved in heparan sulfate and heparin biosynthesis. EXTL2 shows GlcNAc-transferase activity against analogues of the linkage tetrasaccharide substrates (GlcAb1-3Gabl1-O-naphthalenemethanol, GlcAb1-3Gabl1-O-C2H4NHCbz), suggesting that it may have GlcNAcT-I activity in the initiation of heparan sulfate biosynthesis. In vitro substrate specificity analysis showed that this enzyme also showed activity to transfer N-acetylgalactosamine (GalNAc) to oligosaccharide of the linkage tetrasaccharide (GlcAb1-3Gabl1-3Galb1-4Xylb1-O-Ser). It has been suggested that EXTL2 functions as a chain terminator of HS and influences the elongation of heparan sulfate and heparin through experiments in which the expression of EXTL2 gene is varied. Other members of the EXT gene family also possess glycosyltransferase activity involved in heparan sulfate and heparin synthesis, but unlike EXT1 and EXT2, EXTL2 has not been reported to be associated with hereditary multiple exostoses (HME). On the other hand, it has been reported that the EXTL2 (and EXTL3) genes are useful targets for the treatment of Sanfilippo C syndrome.