Exostosin glycosyltransferase 2 (EXT2)

Exostosin glycosyltransferase 2 (EXT2) is a type II transmembrane glycosyltransferase enzyme primarily localized to the Golgi apparatus, where it forms a heterooligomeric complex with exostosin glycosyltransferase 1 (EXT1). Working as a heparan sulfate polymerase, EXT2 catalyzes the elongation of the heparan sulfate glycan backbone by alternating addition of glucuronic acid and N-acetylglucosamine residues, crucial for extracellular matrix composition and cellular signaling. Mutations in EXT2 cause hereditary multiple exostoses (type II), an autosomal dominant disorder characterized by multiple benign bone outgrowths (osteochondromas), with a risk of progression to chondrosarcoma. EXT2 acts as a tumor suppressor, and its loss disrupts normal bone and cartilage development, impairs heparan sulfate biosynthesis, and alters various signaling pathways integral to growth plate function and tissue homeostasis. There are no currently approved drugs that directly target EXT2, but its gene status serves as a diagnostic biomarker for hereditary exostoses syndromes.

Other names

Exostosin-2SOTVGlucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferaseHeparan sulfate co-polymerase subunit EXT2Multiple exostoses protein 2N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferaseSSMSputative tumor suppressor protein EXT2