Mannosyl-glycoprotein N-acetylglucosaminyltransferase (MGAT)

Mannosyl-glycoprotein N-acetylglucosaminyltransferases (MGATs) are a family of Golgi-resident enzymes essential for the structural diversification of N-linked glycans on proteins (UniProt: P26391, Q10469). These enzymes, including MGAT1, MGAT2, MGAT3, MGAT4, and MGAT5, catalyze the transfer of N-acetylglucosamine (GlcNAc) from UDP-GlcNAc to specific mannose residues on the glycan core, thereby initiating the formation of complex branched structures known as antennae (PMID: 19272177). MGAT1 and MGAT2 are required for the synthesis of all complex N-glycans, while MGAT4 and MGAT5 increase branching complexity, which is frequently upregulated in malignant cells to promote growth factor signaling, cell migration, and metastasis (PMID: 18487371). Conversely, MGAT3 adds a bisecting GlcNAc that typically inhibits further branching and can act as a tumor suppressor (PMID: 24511055). Because aberrant N-glycan branching is a hallmark of cancer progression and metabolic dysfunction, these enzymes are significant therapeutic targets, with research focusing on small-molecule inhibitors to modulate glycan profiles in oncology and inflammatory diseases (PMID: 30242148). However, systemic inhibition of these enzymes poses a high risk of developmental toxicity and symptoms resembling Congenital Disorders of Glycosylation (CDG) (PMID: 22230524).

Other names

N-acetylglucosaminyltransferaseGlcNAc-transferaseGnTN-glycosyltransferaseMannosyl-glycoprotein N-acetylglucosaminyltransferase 1Mannosyl-glycoprotein N-acetylglucosaminyltransferase 2Mannosyl-glycoprotein N-acetylglucosaminyltransferase 3Mannosyl-glycoprotein N-acetylglucosaminyltransferase 4Mannosyl-glycoprotein N-acetylglucosaminyltransferase 5

Inhibition of enzyme activity to prevent the formation of complex or branched N-glycan structures on cell surface receptors and secreted proteins, thereby modulating signaling and cell adhesion (PMID: 18487371).