Beta-1,4-N-acetyl-galactosaminyltransferase 2 (B4GALNT2)

Beta-1,4-N-acetyl-galactosaminyltransferase 2 (B4GALNT2) is a type II transmembrane glycosyltransferase responsible for the final step in the biosynthesis of the human Sd(a) and Cad histo-blood group antigens, by transferring N-acetylgalactosamine (GalNAc) in a β1,4 linkage to sialylated galactose residues on glycoproteins and glycolipids. B4GALNT2 generates the Sd(a) epitope, found on circulating erythrocytes and secretory glycoproteins, and displays restricted tissue distribution, with high expression in normal colon, kidney, and certain secretory epithelia. B4GALNT2 exists in multiple isoforms, localizes predominantly in the trans-Golgi network, and is regulated at both genetic and epigenetic levels. In colon cancer, B4GALNT2 is frequently downregulated, and its higher expression is associated with improved patient survival, as it inhibits malignant properties and stemness of colon cancer cells. The biosynthesis of Sd(a) antigen by B4GALNT2 is mutually exclusive with that of the cancer-associated sialyl Lewis antigens (e.g., SLe^x^), and thus B4GALNT2 plays a crucial role in glycan-mediated cellular processes including host-pathogen interactions, immune modulation, and possibly organ rejection.

Other names

GALGT2Sda synthaseCad antigen synthaseSd(a) beta-1,4-GalNAc transferaseUDP-GalNAc:Neu5Aca2-3Galb-R beta-1,4-N-acetylgalactosaminyltransferaseBeta-4-N-acetylgalactosaminyltransferase

Not applicable (no drugs established in use or in trials targeting this enzyme).