Nacetylgalactosaminyltransferases

N-acetylgalactosaminyltransferases, also known as ppGalNAc-Ts, are a family of glycosyltransferases that catalyze the transfer of N-acetylgalactosamine (GalNAc) from UDP-GalNAc to serine or threonine residues on polypeptides. This reaction initiates mucin-type O-glycosylation and can produce the Tn antigen if further elongation of the glycan is not performed by other enzymes.

In humans, ppGalNAc-Ts are encoded by a multigene GALNT family and include several isoforms with distinct tissue distributions and substrate preferences. The enzymes are classed as type II transmembrane proteins localized in the Golgi apparatus, featuring a short cytosolic tail, a single transmembrane domain, and a luminal catalytic domain. They often function as homo- or hetero-oligomers, which can influence substrate selection and catalytic efficiency. Substrate specificity is determined by the catalytic domain along with auxiliary regions, enabling complex, tissue-specific patterns of O-glycosylation.

Biological function centers on the initiation of mucin-type O-glycosylation on a wide range of secreted and membrane-bound proteins, including mucins, receptors, and extracellular matrix components. The GalNAc residue serves as a starting point for subsequent glycosylation steps carried out by downstream glycosyltransferases, shaping core structures such as Core 1 and Core 2 that extend and diversify O-glycans.

Clinical relevance is linked to altered expression or mutation of GALNT genes in various diseases. Changes in ppGalNAc-T activity can affect cell surface glycosylation, mucin barrier function, and cell–cell interactions, contributing to cancer progression, metastasis, and certain congenital glycosylation disorders.