sialyltransferases

Sialyltransferases are a family of glycosyltransferase enzymes that catalyze the transfer of sialic acid from the activated donor CMP-sialic acid to terminal positions on glycoprotein and glycolipid chains, producing sialylated glycoconjugates. Most sialyltransferases are localized to the Golgi apparatus where they function as type II transmembrane proteins with a short cytosolic N-terminus, a single transmembrane segment, and a lumenal catalytic domain. The reaction typically forms α2,3-, α2,6-, or α2,8-linkages, determined by the enzyme.

Sialyltransferases are traditionally grouped into four main families based on linkage specificity: ST3Gal (α2,3), ST6Gal (α2,6), ST6GalNAc (α2,6 to GalNAc), and ST8Sia (α2,8, including polysialyltransferases). Donor substrates are usually CMP-sialic acid, and acceptor substrates include galactose residues on N- and O-glycans, LacNAc units, and, in the case of ST6GalNAc, GalNAc residues such as those in the Tn and sialyl-Tn antigens. ST8Sia enzymes can generate long chains of sialic acid (polysialylation) on substrates such as NCAM.

In humans, many sialyltransferases are encoded by multiple genes (for example ST3GAL, ST6GAL, ST6GALNAC, and ST8SIA families), and the enzymes differ in tissue distribution and substrate preference. Functionally, sialylation modulates cell–cell interactions, receptor activity, and stability of glycoproteins and glycolipids, influencing processes from development and immune recognition to inflammation and pathogen interactions.

Clinical relevance includes altered sialylation patterns in cancer and inflammatory diseases, as well as rare congenital disorders of glycosylation resulting from genetic defects in specific sialyltransferase genes.