Oglycosylation

O-glycosylation is a form of protein glycosylation in which sugars are covalently attached to the hydroxyl groups of serine or threonine residues in proteins. In the secretory pathway, most mucin-type O-glycosylation occurs in the Golgi apparatus. The process begins with the transfer of N-acetylgalactosamine (GalNAc) from UDP-GalNAc to Ser/Thr residues, catalyzed by a family of GalNAc-transferases (GALNTs), producing the Tn antigen. Further elaboration yields a range of core structures. The best characterized is core 1, formed by core 1 β1,3-galactosyltransferase (C1GalT1) with its chaperone Cosmc, converting Tn to the galactose-containing Core 1 (T antigen). Core 2 and other cores are generated by branching GlcNAc transferases (GCNT family). The resulting O-glycans are highly diverse and often terminate with sialic acid or other sugars.

O-glycosylation plays roles in protein folding and stability, protection against proteolysis, and modulation of cell–cell and cell–matrix interactions. It is abundant in mucins and cell-surface receptors and contributes to the mucus barrier and signaling. Alterations in O-glycosylation patterns are observed in diseases, including cancer, inflammatory conditions, and congenital disorders of glycosylation (CDG). Distinct from this, intracellular O-glycosylation of serine/threonine residues by O-GlcNAc transferase (OGT), producing O-GlcNAc, occurs in the cytoplasm and nucleus and is dynamically regulated by O-GlcNAcase (OGA).