UDP-N-acetylglucosamine--dolichyl-phosphate N-acetylglucosaminephosphotransferase (DPAGT1)

UDP-N-acetylglucosamine--dolichyl-phosphate N-acetylglucosaminephosphotransferase (DPAGT1) is an essential enzyme localized to the endoplasmic reticulum (ER) membrane that catalyzes the first step of N-linked protein glycosylation (UniProt: P32790). It facilitates the transfer of N-acetylglucosamine-1-phosphate from UDP-GlcNAc to dolichyl phosphate to form dolichyl-pyrophosphate-GlcNAc, the precursor for all N-glycans (NCBI Gene: 1755). This enzyme serves as a metabolic checkpoint, as its activity levels regulate the flux through the N-glycosylation pathway, impacting the stability and function of numerous glycoproteins including E-cadherin and various receptors (PubMed: 22492577). Mutations in the DPAGT1 gene lead to severe metabolic disorders such as Congenital Disorder of Glycosylation type Ij (CDG-Ij) and Congenital Myasthenic Syndrome (PubMed: 23022097). While the natural product tunicamycin is a well-characterized inhibitor of DPAGT1, its lack of specificity and induction of ER stress have limited its therapeutic application, though the enzyme is increasingly studied as a target in cancer therapy to disrupt aberrant glycosylation (PubMed: 25103495). The regulation of DPAGT1 is also linked to the Wnt/beta-catenin signaling pathway, making it a focal point for understanding epithelial-mesenchymal transition in tumors (PubMed: 21047778).

Other names

GlcNAc-1-P transferaseGPTUDP-GlcNAc:dolichyl-phosphate N-acetylglucosaminephosphotransferaseDolichyl-phosphate alpha-N-acetylglucosaminyltransferaseALG7DPAGT

Inhibition of the transfer of N-acetylglucosamine-1-phosphate to dolichyl phosphate, thereby blocking the initial and rate-limiting step of the dolichol-linked oligosaccharide pathway for N-glycan biosynthesis.