EXTL2

JCGG-STR003511		JCGG-STR033554

JCGG-STR027299		JCGG-STR033555

JCGG-STR033556		JCGG-STR033557

JCGG-STR003511		JCGG-STR033551

JCGG-STR003511		JCGG-STR033551

JCGG-STR033552		JCGG-STR033553

EXTL 2 encodes exostosin-like glycosyltransferase 2. This gene belongs to multiple exostoses (EXT) family and is involved in heparan sulfate and heparin biosynthesis. The main structure of heparan sulfate is a disaccharide repeating structure consisting of (GlcNAcα1-4GlcAβ1-4) and EXTL2 isα1,4-N-acetylglucosaminyltransferase that transfers GlcNAc to the non-reducing terminal of GlcA by the α1,4 bond mainly during chain length extension process.
It transfers the first GlcNAc to the glycosaminoglycan-protein binding region (linkage tetrasaccharide structure: GlcAb1-3Gabl1-3Galb1-4Xylb1-O-Ser) which is the basic skeleton of glycosaminoglycan, and the key enzyme (Initiation enzyme: GlcNAcT-I), which is the starting point of the disaccharide repeat structural synthesis, competes with the synthetase of the chondroitin sulfate and dermatan sulfate biosynthesized on the same linkage tetrasaccharide structure. Transfer of the first GlcNAc by this GlcNAcT-I leads to promotion of biosynthesis of heparan sulfate and heparin. Since EXTL2 shows GlcNAc transferring activity against the analog sugar substrate of linkage tetrasaccharide (GlcAb1-3Gabl1-O-naphthalenemethanol, GlcAb1-3Gabl1-O-C2H4NHCbz), it is suggested that it may have GlcNAcT-I activity.
In addition, it has also been reported that in “in vitro” substrate specificity analysis, this enzyme shows activity that transfers N-acetylgalactosamine (GalNAc) to the linkage tetrasaccharides (GlcAb1-3Gabl1-3Galb1-4Xylb1-O-Ser) etc. Through the experiments that change the expression of EXTL2 gene, it is suggested that EXTL2 functions as a chain terminator of HS and may influence the elongation of heparan sulfate and heparin.
Other genes from EXT family also have glycosyltransferase activity related to synthesis of both the heparan sulfate and heparin, but unlike EXT 1, EXT 2, etc., no association with Hereditary multiple exostoses (HME) has been reported for EXTL2. Meanwhile, in Sanfilippo C syndrome, it is reported that the EXTL2 (and EXTL3) gene is useful as a target of its treatment (therapeutic drug development).

Heparan Sulfate Heparin

Glc	Man	Gal	GlcNAc	GalNAc	Fuc	Xyl	Neu5Ac	Neu5Gc	GlcA	IdoA	GlcN