GalNActransferases

GalNAc transferases, officially known as polypeptide N-acetylgalactosaminyltransferases (ppGalNAc-Ts), are a family of Golgi-resident glycosyltransferases that initiate mucin-type O-glycosylation. They catalyze the transfer of N-acetylgalactosamine (GalNAc) from UDP-GalNAc to serine or threonine residues on polypeptides, generating the Tn antigen when subsequent elongation is absent.

Most family members are type II transmembrane proteins that contain a short cytosolic tail, a single transmembrane segment, a stem region, and luminal catalytic and lectin domains. The catalytic domain transfers GalNAc to acceptor Ser/Thr residues, while the C-terminal lectin-like domain contributes substrate recognition and can influence site selectivity in some isoforms. Together, these domains help determine initiation efficiency and the pattern of O-glycosylation on target proteins.

In humans, the GALNT gene family comprises multiple members (commonly GALNT1–GALNT14), with overlapping but tissue-specific expression patterns. Different GALNT enzymes can act redundantly or cooperatively, shaping the O-glycan profiles on mucins, receptors, and secreted proteins.

Biological significance is broad: O-glycosylation affects protein stability, folding, proteolysis, and interactions, and can modulate signaling pathways and cell adhesion. Dysregulation of GALNT expression or function has been linked to cancer progression, inflammatory diseases, and congenital glycosylation disorders in certain contexts.

Ongoing research aims to define substrate specificities, regulatory mechanisms, and the potential of GALNT enzymes as therapeutic targets to modulate mucin-type glycosylation.