GnTIII

GnTIII, also known as N-acetylglucosaminyltransferase III, is a Golgi-resident type II transmembrane glycosyltransferase encoded by the MGAT3 gene. It catalyzes the transfer of N-acetylglucosamine from UDP-GlcNAc to the core mannose of N-linked glycans on glycoproteins, producing a bisecting GlcNAc structure.

This enzyme acts on mature N-glycans and its action creates a bisected core that inhibits further processing by other N-acetylglucosaminyltransferases, particularly MGAT2 and MGAT4/MGAT5. As a result, the formation of highly branched N-glycan forms is reduced, and the overall glycan architecture on glycoproteins is altered. The presence of a bisecting GlcNAc can influence lectin binding, receptor interactions, and protein trafficking.

Biological significance of GnTIII includes modulation of glycoprotein folding, stability, and cell-surface interactions. It can affect signaling pathways and immune recognition by altering glycan-mediated interactions. In antibodies, bisected Fc glycans modify the affinity for Fc receptors and can impact effector functions such as antibody-dependent cellular cytotoxicity. In cancer biology, MGAT3 expression and the resulting bisected glycans are often linked to altered tumor cell behavior, with many studies reporting reduced MGAT3 activity in metastatic contexts, a finding interpreted as context-dependent and tissue-specific.

Regulation and genetics: MGAT3 expression is tissue-specific and subject to regulatory controls, including epigenetic influences. Aberrant MGAT3 activity and changes in N-glycan profiles are observed in various diseases, including cancer and autoimmunity. GnTIII is part of the MGAT gene family, alongside MGAT1, MGAT2, MGAT4, and MGAT5.