Polypeptide N-acetylgalactosaminyltransferase 4 (GalNAc-T4)

Polypeptide N-acetylgalactosaminyltransferase 4 (GalNAc-T4) is an enzyme in the UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase family that initiates mucin-type O-linked glycosylation in the Golgi apparatus by transferring GalNAc to serine and threonine residues of substrate proteins. The enzyme is a type II transmembrane protein consisting of an N-terminal cytoplasmic region, a transmembrane anchor, a stem region, a catalytic GT-A fold domain, and a C-terminal ricin/lectin-like domain. GalNAc-T4 exhibits both short-range and long-range substrate preferences: it preferentially glycosylates serine/threonine residues just C-terminal to a pre-existing N-terminal glycosylated site on the substrate, a specificity determined by its catalytic and lectin domains connected via a flexible linker. The structure and substrate specificity of GalNAc-T4 distinguish it from related transferase isoforms, making it important both for the initial steps of mucin-type O-glycosylation and for the consequent structural and functional diversity of glycoproteins in health and disease. No direct therapeutic agents targeting GalNAc-T4 are approved or in late-stage clinical development, but dysregulation of GalNAc-T4 and related enzymes is widely implicated in cancer and other pathological states.

Other names

GALNT4UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 4Polypeptide GalNAc-transferase 4GalNAc-T4

Catalyzes the transfer of an N-acetylgalactosamine molecule from UDP-GalNAc to the hydroxyl group of a serine or threonine residue in polypeptides. Prefers glycopeptide substrates with an N-terminally glycosylated threonine, recognizes polypeptide sequence and prior glycosylation state through distinct catalytic and lectin domains.