Protein O-linked mannose N-acetylglucosaminyltransferase 2 (POMGNT2)

Protein O-linked mannose N-acetylglucosaminyltransferase 2 (POMGNT2) is an enzyme of the glycosyltransferase family, specifically responsible for transferring N-acetylglucosamine (GlcNAc) in a beta-1,4-linkage to O-linked mannose residues on proteins, primarily during post-translational modification of alpha-dystroglycan (α-DG). This biochemical step is critical in the synthesis of the core M3-type O-mannosyl glycan, which is essential for α-DG to bind the extracellular matrix and for proper muscle and brain development. Disruptions or mutations in the POMGNT2 gene lead to reduced or absent functional glycosylation of alpha-dystroglycan, resulting in a spectrum of severe muscular dystrophies known as dystroglycanopathies, with variable involvement of the central nervous system and eyes. POMGNT2 acts in the endoplasmic reticulum and displays strict substrate selectivity, targeting particular O-mannosylation sites with specific sequence motifs (notably the TPT motif in α-DG). Structural studies reveal unique substrate recognition modes, and POMGNT2 mutations are mechanistically associated with disease through loss of this precise enzymatic activity. No drugs are known to modulate POMGNT2 activity directly; thus, it presently is not a direct pharmacological target, though it is a crucial pathogenic factor in these lethal genetic disorders.

Other names

GTDC2Beta-1,4-N-acetylglucosaminyltransferase 2Protein O-linked-mannose beta-1,4-N-acetylglucosaminyltransferase 2PMGT2 protein

Not applicable; no drugs are known to target this enzyme directly as of the current evidence.