Alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase (MGAT5) (MGAT5)

Alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase, commonly known as MGAT5 or GnT-V, is a Golgi-resident enzyme essential for the complex branching of N-linked glycans [1, 2]. It catalyzes the addition of N-acetylglucosamine (GlcNAc) to the alpha-1,6-linked mannose of the N-glycan core, forming beta-1,6-GlcNAc branches [1]. This specific glycosylation pattern is a hallmark of cancer progression, as it enhances the stability and signaling of growth factor receptors, such as EGFR and TGF-beta receptors, on the cell surface, thereby promoting tumor invasion and metastasis [3]. In addition to its role in oncology, MGAT5 is a key regulator of the immune system, where it modulates T-cell receptor signaling and has been linked to the pathogenesis of autoimmune conditions like multiple sclerosis [4]. While no drugs targeting MGAT5 are currently FDA-approved, it remains a significant target for the development of small-molecule inhibitors and glycan-based therapies aimed at disrupting pathological cell signaling in cancer and inflammatory diseases [3, 5].

Other names

N-acetylglucosaminyltransferase VGnT-VGlcNAc-TVMannoside acetylglucosaminyltransferase 5MGAT5

Inhibition of the enzymatic transfer of N-acetylglucosamine to the alpha-1,6-linked mannose of N-glycans to prevent beta-1,6-branching.